PMID- 21006453 TI - Culture methods in the diagnosis of amoebiasis. PMID- 21006454 TI - Neuroparalytic accident following anti-rabic vaccination. PMID- 21006455 TI - Investigation of the fungistatic activity of reagents that might be suitable for use in the treatment of epidermophytosis. PMID- 21006456 TI - An aerodynamic suit for the protection of pilots against black-out. PMID- 21006457 TI - The scientist's interference with the things he studies. PMID- 21006458 TI - AUSTRALIAN activities in the field of human nutrition. PMID- 21006459 TI - [Not Available]. PMID- 21006460 TI - [Not Available]. PMID- 21006461 TI - [Not Available]. PMID- 21006462 TI - [Not Available]. PMID- 21006463 TI - [Not Available]. PMID- 21006464 TI - [Not Available]. PMID- 21006465 TI - [Not Available]. PMID- 21006466 TI - [Not Available]. PMID- 21006467 TI - [Not Available]. PMID- 21006468 TI - [Not Available]. PMID- 21006469 TI - [Not Available]. PMID- 21006470 TI - [Not Available]. PMID- 21006471 TI - [Not Available]. PMID- 21006472 TI - [Not Available]. PMID- 21006473 TI - [Not Available]. PMID- 21006474 TI - [Not Available]. PMID- 21006475 TI - [Not Available]. PMID- 21006476 TI - [Not Available]. PMID- 21006477 TI - [Not Available]. PMID- 21006478 TI - [Not Available]. PMID- 21006479 TI - TEAM work in science. PMID- 21006481 TI - New basic concepts in electrocardiography; the ventricular gradient. PMID- 21006480 TI - The teaching of analytical chemistry in Great Britain: with special reference to microchemistry. PMID- 21006482 TI - 3:4-benzpyrene from coal tar. PMID- 21006483 TI - Concentration of solutions of salts of penicillin. PMID- 21006484 TI - Sexual differentiation of the gonad and the sexualization of the germ cells in teleosts. PMID- 21006485 TI - British anti-lewisite (BAL). PMID- 21006486 TI - Antimalarial activity in tetrahydroacridones and related substances. PMID- 21006488 TI - Molecular morphology of myosin. PMID- 21006487 TI - Crystallization and identity of the triose and triosephosphate dehydrogenases of muscle. PMID- 21006489 TI - Heat coagulation of muscle proteins. PMID- 21006490 TI - Activity of helvolic acid against Mycobacterium tuberculosis. PMID- 21006491 TI - An illusion of size. PMID- 21006492 TI - THE UNITY of science. PMID- 21006493 TI - Effective and ineffective strains of legume nodule bacteria. PMID- 21006494 TI - Enhancement of the action of immune haem-agglutinins by human serum. PMID- 21006495 TI - Transition of fibrinogen to fibrin as a two-step reaction. PMID- 21006496 TI - The anti-chromatic reflex. PMID- 21006497 TI - Studies on Oxytricha bifaria Stokes; cystic reorganization. PMID- 21006498 TI - Supernucleate cysts of Endamoeba coli and E. histolytica. PMID- 21006499 TI - A quantitative method for the determination of the amebacidal activity of drugs in vitro. PMID- 21006500 TI - The composition of the refractive bodies in the rhizopod Pelomyxa carolinensis. PMID- 21006501 TI - Studies on monogenetic trematodes; Urocleidus seculus, a new species of Tetraonchinae from the viviparous top minnow, Gambusia affinis affinis (Baird and Girard). PMID- 21006502 TI - Two trematodes from a hibernating bat, Myotis californicus. PMID- 21006503 TI - A new genus of monogenetic trematode from Bermuda. PMID- 21006504 TI - A new hymenolepidid cestode, Hymenolepis furcouterina, from a Celebesian black bellied snakebird. PMID- 21006505 TI - Collection and preservation of sandflies (Phlebotomus) with keys to U.S. species (Diptera: Psychodidae). PMID- 21006506 TI - Acute war neurosis; special reference to Pavlov's experimental observations and the mechanism of abreaction. PMID- 21006507 TI - Disturbances in sleep mechanism; a clinicopathologic study; lesions at the corticodiencephalic level. PMID- 21006508 TI - Multiplicity of representation versus punctate localization in the motor cortex. PMID- 21006509 TI - Disseminated oligodendroglioma. PMID- 21006510 TI - Blood supply of peripheral nerves; practical considerations. PMID- 21006511 TI - Blood supply of the sciatic nerve and its popliteal divisions in man. PMID- 21006512 TI - Studies on cerebral edema; reaction of the brain to exposure to air; physiologic changes. PMID- 21006513 TI - Experimental study on treatment of dementia paralytica with penicillin. PMID- 21006514 TI - Common factors precipitating mental symptoms. PMID- 21006515 TI - Hysterical convulsions treated with hypnosis and psychotherapy; report of a case. PMID- 21006516 TI - Use of galvanic tetanus and the galvanic tetanus ratios in electrodiagnosis of lesions of peripheral nerves. PMID- 21006517 TI - The use of psychoanalytic principles in the therapeutic management of an acute psychosis. PMID- 21006518 TI - Short psychoanalytic psychotherapy. PMID- 21006519 TI - Dostoevsky and parricide. PMID- 21006520 TI - Reminiscent notes on the early history of psycho-analysis in English-speaking countries. PMID- 21006521 TI - The Oedipus complex in the light of early anxieties. PMID- 21006522 TI - The concept of trauma in contemporary psycho-analytical theory. PMID- 21006523 TI - The unconscious origin of Schopenhauer's philosophy. PMID- 21006524 TI - A note on ambivalence. PMID- 21006525 TI - Notes on metapsychology as process theory; some comments. PMID- 21006526 TI - Some psychological aspects of prostitution; the pseudo-personality. PMID- 21006528 TI - True and false conceptions of psychoanalysis. PMID- 21006527 TI - The treatment of the psychotic-like regressions of the combat soldier. PMID- 21006529 TI - The treatment of psychoses with methyl guanidine sulfate; a clinical report of 12 cases. PMID- 21006530 TI - Archetype postures; clinical impressions. PMID- 21006531 TI - Schizophrenic-like reactions in children. II. PMID- 21006532 TI - Posthospitalization supportive psychotherapy. PMID- 21006533 TI - The clinical measurement of anxiety; an experimental approach. PMID- 21006534 TI - Psychiatric implications of internal medicine. PMID- 21006536 TI - A short genetic survey of psychic impotence. II. PMID- 21006535 TI - Prevalence of pulmonary tuberculosis in New York State institutions for the mentally ill. PMID- 21006537 TI - A comparison of the Wechsler-Bellevue and the revised Stanford-Binet scales for adult defective delinquents. PMID- 21006539 TI - Further observations on hallucinations of small. PMID- 21006538 TI - The anticonvulsant action of tridione; preliminary report. PMID- 21006540 TI - Institutionalizing the obsessive psychopath. PMID- 21006541 TI - Postwar trends in public health and nursing. PMID- 21006542 TI - Nursing and nursing education in Germany. PMID- 21006543 TI - Nursing aboard a hospital ship. PMID- 21006544 TI - Health program for radium dial workers. PMID- 21006545 TI - One blueprint for recruitment. PMID- 21006546 TI - Opinion molders appraise nursing. PMID- 21006547 TI - The Marianas. PMID- 21006549 TI - Return to the Philippines. PMID- 21006548 TI - They pioneered on Tinian. PMID- 21006550 TI - 5,000 Civilian nurses. PMID- 21006551 TI - 31,000 Army nurses and their postwar plans. PMID- 21006552 TI - Combined immunization against whooping cough, diphtheria, and tetanus. PMID- 21006553 TI - The child on a Bradford frame; diversional therapy. PMID- 21006554 TI - The U.S. Cadet Nurse Corps; a summing up. PMID- 21006555 TI - Convalescent care of children. PMID- 21006556 TI - Insulin therapy in combat exhaustion. PMID- 21006557 TI - Every nurse has a share in the war on cancer. PMID- 21006558 TI - Food handling instructions for nurses. PMID- 21006559 TI - Dentritic keratitis associated with chronic malaria. PMID- 21006560 TI - A comparative study of the bacteriologic flora of nasal and nasopharyngeal membranes of patients with certain ocular disorders. PMID- 21006561 TI - Allergic retinosis. PMID- 21006562 TI - Statistical analysis of 1,000 consecutive new eye patients. PMID- 21006563 TI - A method for the extraction of dislocated lenses from the vitreous. PMID- 21006564 TI - Restoration of patency of the nasolacrimal duct by means of a vitallium tube; a preliminary report. PMID- 21006565 TI - Experiences with the surgery of the anophthalmic orbit. PMID- 21006566 TI - Megalocornea. PMID- 21006567 TI - A new model of contact glass for gonioscopy (goniolens). PMID- 21006568 TI - Ocular sensitivity to butyn. PMID- 21006569 TI - Hinge-flap sclerotomy drainage operations. PMID- 21006570 TI - Familial corneal dystrophy; three cases. PMID- 21006571 TI - Loose flocculus in anterior chamber. PMID- 21006572 TI - Hereditary anterior megalophthalmos. PMID- 21006573 TI - Mikulicz's disease. PMID- 21006574 TI - Detachment of the retina. PMID- 21006575 TI - Sphenoidal-ridge meningioma en plaque. PMID- 21006577 TI - Detachment of retina with multiple tears. PMID- 21006576 TI - Atypical coloboma of the choroid. PMID- 21006578 TI - Thrombosis of retinal vein treated with dicumarol. PMID- 21006579 TI - Plastic repair for cicatricial stenosis of the lacrimal canaliculi. PMID- 21006580 TI - Fusion in esotropia without orthoptic training. PMID- 21006581 TI - Cyst of the iris. PMID- 21006582 TI - Syphilitic iritis with particular reference to the Herxheimer reaction as a diagnostic aid and response to different treatment including penicillin. PMID- 21006583 TI - Commonly used ophthalmic drugs of little value. PMID- 21006584 TI - The Graf Wiser technique in the treatment of refractive abnormalities. PMID- 21006585 TI - Defective color vision in a female patient; a case report. PMID- 21006586 TI - Lighting and safety. PMID- 21006587 TI - A physicist's summary of atomic energy. PMID- 21006588 TI - Ocular manifestations of malnutrition in released prisoners of war from Thailand. PMID- 21006590 TI - A case of occipital lobe injury. PMID- 21006589 TI - Ocular gnathostomiasis. PMID- 21006591 TI - Indirect injury of the optic chiasma; a case report. PMID- 21006592 TI - Retinal haemorrhages in aplastic anaemia. PMID- 21006593 TI - Haemorrhage from the conjunctiva; notes on a case of capillary angioma. PMID- 21006594 TI - A corneal graft operation for recurrent pterygium. PMID- 21006595 TI - Coppock cataract and cataracta pulverulenta centralis. PMID- 21006596 TI - Diabetic needles. PMID- 21006598 TI - Report from the Wilmer Institute on the results obtained in the treatment of myopia by visual training. PMID- 21006597 TI - MEMORANDUM on the notification and certification of the blind, on definitions of blindness, and on blind pensions. PMID- 21006599 TI - Current problems of myopia. PMID- 21006600 TI - INDUSTRIAL ophthalmology. PMID- 21006601 TI - Determining visual standards for industrial jobs by statistical methods. PMID- 21006602 TI - Conservation of hearing; the Cleveland hearing conservation program. PMID- 21006603 TI - Experimental histological studies on the labyrinth. PMID- 21006604 TI - Experimental histological studies on the labyrinth; agonal and post-mortem changes. PMID- 21006605 TI - Experimental histological studies on the labyrinth; the endolymphatic compression (Wittmaack's hypotonic degeneration). PMID- 21006606 TI - [Not Available]. PMID- 21006607 TI - [Not Available]. PMID- 21006608 TI - Hemolytic streptococci in the nose and pharynx; a study on their significance to complications following otorhino-laryngological operations. PMID- 21006609 TI - A case of caseous rhinitis and bilateral caseous maxillary sinusitis. PMID- 21006610 TI - Investigations in the microphone effect of the cochlea with some remarks on a new technique. PMID- 21006611 TI - The surgical treatment of otogenous facial paresis. PMID- 21006612 TI - Experimental histological labyrinth examinations. PMID- 21006613 TI - A peculiar case of subglottic laryngitis. PMID- 21006614 TI - A case of acute suppurative otitis media with tardy occurrence of perisinuous abscess and thrombosis of the sigmoid sinus. PMID- 21006615 TI - Foreign bodies in esophagus and air-passages. PMID- 21006616 TI - Some orienting remarks about tuning-forks and audiometer, and about the registration of defects of hearing. PMID- 21006617 TI - Acute suppurative otitis media in infants. PMID- 21006618 TI - The material of infant patients with otitis media in the Kommunehospital of Copenhagen. PMID- 21006619 TI - Experimental histological studies on the labyrinth; pilocarpine and atropin. PMID- 21006620 TI - Cases of familial esophagus stricture. PMID- 21006621 TI - Local sulfathiazole treatment of the wound cavity after mastoidectomy in acute mastoiditis. PMID- 21006622 TI - Orbital complications following operations on paranasal sinuses. PMID- 21006623 TI - [Not Available]. PMID- 21006624 TI - Local treatment with sulfathiazole in sinusitis. PMID- 21006625 TI - Osteomyelitis necroticans faciei. PMID- 21006626 TI - The genesis of typical and atypical cysts of the nasal floor. PMID- 21006627 TI - Bilateral perforate nasopalatine communication in the human adult. PMID- 21006628 TI - The conservative treatment of chronic suppurative otitis media. PMID- 21006629 TI - Results of treatment of carcinoma of the larynx by x-ray at operation. PMID- 21006630 TI - Interpretative reading as an aid to speech correction, acting, and radio. PMID- 21006631 TI - Suggestions for a successful speech correction program in public schools. PMID- 21006632 TI - The semantic aspects of stuttering in non-stutterers: additional data. PMID- 21006633 TI - On the coliform bacteria of human feces. PMID- 21006634 TI - [Not Available]. PMID- 21006635 TI - Studies in hereditary dwarfism in mice; the histology of the anterior pituitary of mice with hereditary adiposity and of dwarf mice with hereditary adiposity. PMID- 21006636 TI - [Not Available]. PMID- 21006637 TI - The action of the pituitary gland on the growth of mice shown by parabiosis. PMID- 21006638 TI - Capsular antigens common to a streptococcus strain and some pneumococcus types. PMID- 21006639 TI - Theoretical and practical results from employment of indigo carmine in studies on anaerobic bacteria. PMID- 21006640 TI - [Not Available]. PMID- 21006641 TI - Extensive arterial calcification and cirrhosis of the liver in a newborn infant. PMID- 21006642 TI - The Widal reaction in Sonne dysentery. PMID- 21006643 TI - The use of yeast autolysate as activator in the preparation of diphtheria toxin. PMID- 21006644 TI - Chemical control of the phenol contents of vaccines and serum preparations. PMID- 21006645 TI - Histology of the liver in diseases of the stomach. PMID- 21006646 TI - Studies on methods for protraction of the effect of penicillin. PMID- 21006647 TI - Lysis of red blood cells by tissue slices. PMID- 21006648 TI - The arginine, ornithine and carbon dioxide requirements of streptococci (Lancefield group D) and their relation to arginine dihydrolase activity. PMID- 21006649 TI - The effect of sulphanilamide on the arginine and carbon dioxide requirements of streptococci (Lancefield group D). PMID- 21006650 TI - The examination of rabbit anti-A immune sera produced by means of an artificial A antigen. PMID- 21006651 TI - A new test for the detection of weak and incomplete Rh agglutinins. PMID- 21006652 TI - Comparative potency of the mammary tumour agent of mice of different genetic constitution. PMID- 21006653 TI - Experimental nodular goitre. PMID- 21006654 TI - Measurement of circulating ragweed antigen. PMID- 21006655 TI - Quantitative estimation of the absorption of an ingested allergen. PMID- 21006656 TI - A quantitative study of the relation of synthetic 3-pentadecyl catechol to hypersensitiveness to Rhus toxicodendron (poison ivy) as shown by the patch test. PMID- 21006657 TI - Spontaneous mediastinal and subcutaneous emphysema complicating bronchial asthma; report of an additional case and analysis of 25 previously reported cases. PMID- 21006658 TI - Mold allergy; field survey of Philadelphia area. PMID- 21006659 TI - Relief of dermographism and other urticarias of histamine origin by a synthetic benzhydryl alkamine ether. PMID- 21006660 TI - Contact dermatitis due to contact with chrome 17 per cent steel identification tags of the United States Navy. PMID- 21006661 TI - ALLERGY to penicillin. PMID- 21006662 TI - [Not Available]. PMID- 21006663 TI - [Not Available]. PMID- 21006664 TI - [Not Available]. PMID- 21006665 TI - [Not Available]. PMID- 21006666 TI - [Not Available]. PMID- 21006667 TI - [Not Available]. PMID- 21006668 TI - [Not Available]. PMID- 21006670 TI - [Not Available]. PMID- 21006669 TI - [Not Available]. PMID- 21006671 TI - [Not Available]. PMID- 21006672 TI - [Not Available]. PMID- 21006673 TI - [Not Available]. PMID- 21006674 TI - [Not Available]. PMID- 21006675 TI - [Not Available]. PMID- 21006676 TI - Salicylates in the treatment of rheumatic patients. PMID- 21006677 TI - Children's idiosyncrasies. PMID- 21006678 TI - Changing trends in diphtheria in San Francisco. PMID- 21006679 TI - Gonorrheal vaginitis in children. PMID- 21006680 TI - The road to rehabilitation; good teamwork by professional workers helps crippled children to lead normal lives. PMID- 21006681 TI - Ten years of progress in reducing maternal and infant mortality. PMID- 21006682 TI - Century old botanicals. PMID- 21006684 TI - Alcohol beverages and genus Homo sapiens. PMID- 21006683 TI - The comparative toxicity and effectiveness of scopolamine hydrobromide (C17H21O4N.HBr) and scopolamine aminoxide hydrobromide (C17H21O5N HBr). PMID- 21006685 TI - Proteins come of age. PMID- 21006686 TI - Tropical diseases. PMID- 21006687 TI - PENICILLIN supply and demand. PMID- 21006688 TI - Streptomycin. PMID- 21006689 TI - The sprue syndrome. PMID- 21006690 TI - Penicillin lozenges. PMID- 21006691 TI - FURTHER studies in penicillin therapy. PMID- 21006692 TI - Malt and extract of malt. PMID- 21006693 TI - The drug resources of North West Frontier Province. PMID- 21006694 TI - A review of sulphonamide preparations. PMID- 21006695 TI - What shall we do with uranium? PMID- 21006696 TI - The sterilisation of surgical dressings. PMID- 21006697 TI - The effect of cH on humoral stimulation of striated muscle and its application to the chemical control of breathing. PMID- 21006698 TI - The beneficial effects of yeast on the cardiac failure of hyperthyroid rats. PMID- 21006699 TI - Growth and hemoglobin production in dogs on purified rations. PMID- 21006700 TI - Gonadotropic activity of equine gonadotropin in combination with zinc. PMID- 21006701 TI - Liver water and electrolytes in hemorrhagic shock. PMID- 21006702 TI - The production of arterial hypertension by chronic renal artery-nerve stimulation. PMID- 21006703 TI - Functional changes in nerve and muscle after partial denervation. PMID- 21006704 TI - Blood regeneration in rats deficient in biotin, thiamin or riboflavin. PMID- 21006705 TI - The effect of calcium concentration on prothrombin time. PMID- 21006706 TI - The distribution of phosphorus compounds in the gastrocnemius muscle as influenced by the ageing process. PMID- 21006707 TI - Biological energy transformation during shock as shown by blood chemistry. PMID- 21006708 TI - A comparison of the nutritive value of dextrose and of corn syrups and of the effects produced on their utilization by thiamine. PMID- 21006709 TI - Note on the effect of caffeine on ammonia and urea excretion in rabbits. PMID- 21006710 TI - The effect of various steroid hormones on the alkaline and acid phosphatases of the kidney of the mouse. PMID- 21006711 TI - The behavioral sequelae of neurosurgical therapy (bilateral prefrontal lobotomy). PMID- 21006712 TI - An investigation of the nature of non-directive psychotherapy. PMID- 21006713 TI - Studies in discrimination learning by monkeys; discriminations between stimuli differing in both color and form, and only in color, and only in form. PMID- 21006714 TI - The emotional element in music. PMID- 21006715 TI - The meaning-frequency relationship of words. PMID- 21006716 TI - A study of types of word-association in dementia praecox and manic-depressives. PMID- 21006717 TI - A twenty-five year review of the work of the Committee on Administrative Practice. PMID- 21006718 TI - Recent trenas in the early diagnosis of tuberculosis. PMID- 21006719 TI - Prevalence of rheumatic heart disease in Denver school children. PMID- 21006720 TI - A public health role for the laundry. PMID- 21006721 TI - Distribution of Shigella in India as determined by spot agglutination with absorbed sera. PMID- 21006722 TI - Background of current trends in the relation of public health to medical care. PMID- 21006723 TI - A method for control of sanitation in food processing plants. PMID- 21006725 TI - Treatment of pediculosis capitis. PMID- 21006724 TI - Problems of health education in Latin-America. PMID- 21006726 TI - Public health degrees and certificates granted in the United States and Canada, during the academic year. PMID- 21006727 TI - [Not Available]. PMID- 21006728 TI - Tonsillectomy in the school medical service; indications. PMID- 21006729 TI - The control of cockroaches. PMID- 21006730 TI - ERADICATION of bed-bugs; a further note. PMID- 21006732 TI - Trading the source of infection in cases of tuberculous meningitis of bovine origin. PMID- 21006731 TI - Studies on the isolation of Bact. typhosum and Bact. paratyphosum B. PMID- 21006733 TI - Operation of activated sludge plants. PMID- 21006734 TI - Water treatment to reduce chemical odors; experience with various methods at Nitro, W. Va. PMID- 21006735 TI - Training; a new conception; the nucleus of a suggested scheme for the training of radiographers from school-leaving age, with remuneration, compared with the present scheme. PMID- 21006736 TI - The principles of encephalography. PMID- 21006737 TI - Modified angle block. PMID- 21006738 TI - History of military radiographic training. PMID- 21006739 TI - Surgical treatment of long-standing deep phlebitis of the leg; a supplementary report. PMID- 21006740 TI - Venous pressures in disorders of the venous system of the lower extremities. PMID- 21006741 TI - Surgical correction for coarctation of the aorta. PMID- 21006742 TI - Arteriovenous fistula; a suture technique for producing a lateral anastomosis, an experimental study. PMID- 21006743 TI - Successful removal of foreign bodies within the pericardium; a report of two cases. PMID- 21006744 TI - A routine for early skin grafting of deep burns. PMID- 21006745 TI - The intrahilar and related segmental anatomy of the lung. PMID- 21006746 TI - A new design for raising a tubed pedicled flap. PMID- 21006747 TI - Resuscitation of severely wounded casualties. PMID- 21006748 TI - The peritoneal absorption of penicillin. PMID- 21006749 TI - The molded bone graft. PMID- 21006751 TI - Herniation of nucleus pulposus; refinement in operative technique. PMID- 21006750 TI - Nylon bone suture. PMID- 21006753 TI - A method of retaining an intravenous needle in situ. PMID- 21006752 TI - Chylangioma cavernosum mesenterii; report of a case and review of the literature. PMID- 21006754 TI - Traumatic aneurysm; the Matas operation 57 years after. PMID- 21006755 TI - War injuries of the chest. PMID- 21006756 TI - Intravenous gelatin for nutritional purposes. PMID- 21006757 TI - Indications for roentgen therapy of bladder carcinomas. PMID- 21006758 TI - Reflex sympathetic dystrophy. PMID- 21006759 TI - A single-stage operative method of management of chronically infected, ununited fractures. PMID- 21006760 TI - The saphenous venous tributaries and related structures in relation to the technique of high ligation; based chiefly upon a study of 550 anatomical dissections. PMID- 21006761 TI - Thoracoabdominal wounds; a review of 270 cases. PMID- 21006762 TI - Decortication in acute empyema thoracis. PMID- 21006764 TI - Acquired esophagotracheobronchial fistula. PMID- 21006763 TI - Osteogenic sarcoma; roentgenographic interpretation of growth patterns in bone sarcoma. PMID- 21006765 TI - Gunshot fractures of the femoral shaft. PMID- 21006766 TI - The diagnosis of acute flexor tendon tenosynovitis. PMID- 21006767 TI - Strictures of the common duct. PMID- 21006768 TI - Intravenous amino acids, protein digests; accuracy of terminology. PMID- 21006769 TI - New technique of simultaneous bilateral uretero-intestinal anastomosis; report of experimental study. PMID- 21006770 TI - Lumbar ureterolithotomy; the Foley operation. PMID- 21006771 TI - Congenital valve in the upper ureter. PMID- 21006772 TI - Unilateral triplication of the ureter and renal pelvis. PMID- 21006773 TI - The use of thrombin (topical) in the control of bleeding associated with prostatic surgery. PMID- 21006774 TI - Incarceration of the penis. PMID- 21006775 TI - The use of the antidiuretic property of pitressin in excretory pyelography. PMID- 21006776 TI - Sulfadiazine anuria with urethral stricture. PMID- 21006777 TI - The application of a new plastic cast material in urology. PMID- 21006778 TI - The medical kidney. PMID- 21006779 TI - Penicillin resistant abacterial pyuria. PMID- 21006780 TI - Coexisting lesions in the female reproductive and urinary tracts. PMID- 21006781 TI - Urine retention and arterial hypertension. PMID- 21006782 TI - Perineal adenomectomy of the prostate. PMID- 21006783 TI - The central control of micturition. PMID- 21006784 TI - Prevention of surgical complications of the lower urinary tract. PMID- 21006785 TI - Keratoderma dissemination hereditarium palmare et plantare; report of a case. PMID- 21006787 TI - Medieval prostitution. PMID- 21006786 TI - Puerperal pelvic thrombosis; with report of a case. PMID- 21006788 TI - Thrombosis and thrombophlebitis of the renal veins. PMID- 21006789 TI - End results in the treatment of bladder tumors. PMID- 21006790 TI - Has the prostate gland an internal secretion? PMID- 21006791 TI - Neurologic manifestations during arsenotherapy for syphilis. PMID- 21006792 TI - Allergic neurodermatitis. PMID- 21006793 TI - Highlights of the Conference in tropical dermatology for American doctors. PMID- 21006795 TI - [Not Available]. PMID- 21006794 TI - The nail and its diseases. PMID- 21006796 TI - [Not Available]. PMID- 21006797 TI - [Not Available]. PMID- 21006798 TI - [Not Available]. PMID- 21006799 TI - [Not Available]. PMID- 21006800 TI - [Not Available]. PMID- 21006801 TI - [Not Available]. PMID- 21006802 TI - [Not Available]. PMID- 21006803 TI - Checklist of the internal and external animal parasites of domestic animals in North America (United States and possessions and Canada). PMID- 21006804 TI - Studies on swine enteritis; Salmonella and other enteric organisms isolated from diseased and normal swine. PMID- 21006805 TI - An active agent isolated from hogs affected with arthritis; preliminary report. PMID- 21006806 TI - The colostrum pregnancy test in cattle. PMID- 21006807 TI - The effect of low outdoor temperatures on the free-living stages of some common nematode parasites of sheep. PMID- 21006808 TI - Salmonella types isolated from snakes. PMID- 21006809 TI - Some preliminary observations on the effect of molybdenum on copper metabolism in herbivorous animals. PMID- 21006810 TI - An acute case of parturient haemoglobinaemia. PMID- 21006811 TI - Children's infections and their control in the USSR in the years of the Great Patriotic War. PMID- 21006812 TI - The problem of whooping cough; the present stage and further research. PMID- 21006813 TI - On the clinics and pathogenesis of whooping cough pneumonias. PMID- 21006814 TI - Pathomorphology of pulmonary deformations in whooping cough. PMID- 21006815 TI - Some data on epidemiology of diphtheria and scarlet fever in the years of the Patriotic War. PMID- 21006816 TI - Contribution to the etiology of scarlet fever. PMID- 21006817 TI - The significance of hemolytic streptococcus in contagiousness of scarlet fever and continuance of the infectious period in the scarlatinous reconvalescent. PMID- 21006818 TI - Experimental measles in monkeys. PMID- 21006819 TI - Characteristics of the hemolytic streptococci excreted by the measles patient showing purulent complications. PMID- 21006820 TI - On the etiology and pathogenesis of toxic diphtheria. PMID- 21006821 TI - On the etiology and pathogenesis of toxic diphtheria. PMID- 21006822 TI - Contribution to the epidemiology of diphtheria. PMID- 21006823 TI - Efficiency of annual immunization against diphtheria. PMID- 21006824 TI - On the immune state of the organism in various methods of antidiphtheritic vaccination. PMID- 21006826 TI - Laboratory study of diphtheria extrafaucialis. PMID- 21006825 TI - Characteristics of diphtheria bacilli-carrying at Krasnoyarsk during 1943. PMID- 21006827 TI - Media for typing of diphtheria bacilli. PMID- 21006828 TI - Sulphidin in the prophylaxis of epidemic cerebrospinal meningitis. PMID- 21006829 TI - New data on rabies. PMID- 21006830 TI - Some data on bacteriological characteristics of pneumonia in dystrophics. PMID- 21006831 TI - Garro's elective medium? PMID- 21006832 TI - The architecture of the cerebral capillary bed. PMID- 21006833 TI - The effect of neurohypophysial extracts on the water balance of lower vertebrates. PMID- 21006834 TI - Biological methylation. PMID- 21006835 TI - On the use of matrices in certain population mathematics. PMID- 21006836 TI - Errors in the routine daily measurement of the puerperal uterus. PMID- 21006837 TI - On a method of estimating frequencies. PMID- 21006838 TI - The mathematics of a population composed of kappa stationary strata each recruited from the stratum below and supported at the lowest level by a uniform annual number of entrants. PMID- 21006839 TI - Moments of gamma and chi 2 for a fourfold table in the absence of association. PMID- 21006840 TI - The use of chi 2 as a test of homogeniety in a (mu chi 2)-fold table when expectations are small. PMID- 21006841 TI - The treatment of ties in ranking problems. PMID- 21006842 TI - The probability integral of the mean deviation. PMID- 21006843 TI - On the distribution of the estimate of mean deviation obtained from samples from a normal population. PMID- 21006844 TI - Note on the calculation of the distribution of the estimate of mean deviation in normal samples. PMID- 21006845 TI - TABLES of the probability integral of the mean deviation in normal samples. PMID- 21006846 TI - Chain processes and their biophysical applications; general theory. PMID- 21006847 TI - The flow of a viscous fluid in an elastic tube; a model of the femoral artery. PMID- 21006848 TI - A contribution to the mathematical biophysics of cell growth and shapes. PMID- 21006849 TI - Some remarks on the Boolean algebra of nervous nets in mathematical biophysics. PMID- 21006850 TI - Some quantitative aspects of shock therapy in psychoses. PMID- 21006851 TI - A note on the mathematical biophysics of central excitation and inhibition. PMID- 21006852 TI - A suggestion for another statistical interpretation of the fundamental equations of the mathematical biophysics of the central nervous system. PMID- 21006853 TI - The heterarchy of values determined by the topology of nervous nets. PMID- 21006854 TI - [Not Available]. PMID- 21006855 TI - [Not Available]. PMID- 21006856 TI - [Not Available]. PMID- 21006857 TI - [Not Available]. PMID- 21006858 TI - [Not Available]. PMID- 21006859 TI - [Not Available]. PMID- 21006860 TI - [Not Available]. PMID- 21006861 TI - [Not Available]. PMID- 21006862 TI - [Not Available]. PMID- 21006863 TI - [Not Available]. PMID- 21006864 TI - [Not Available]. PMID- 21006865 TI - [Not Available]. PMID- 21006866 TI - [Not Available]. PMID- 21006867 TI - [Not Available]. PMID- 21006868 TI - [Not Available]. PMID- 21006869 TI - [Not Available]. PMID- 21006870 TI - [Not Available]. PMID- 21006871 TI - [Not Available]. PMID- 21006872 TI - [Not Available]. PMID- 21006873 TI - [Not Available]. PMID- 21006874 TI - [Not Available]. PMID- 21006875 TI - [Not Available]. PMID- 21006876 TI - [Not Available]. PMID- 21006877 TI - [Not Available]. PMID- 21006878 TI - [Not Available]. PMID- 21006879 TI - [Not Available]. PMID- 21006880 TI - [Not Available]. PMID- 21006881 TI - [Not Available]. PMID- 21006882 TI - [Not Available]. PMID- 21006883 TI - [Not Available]. PMID- 21006884 TI - [Not Available]. PMID- 21006885 TI - [Not Available]. PMID- 21006886 TI - [Not Available]. PMID- 21006887 TI - [Not Available]. PMID- 21006888 TI - [Not Available]. PMID- 21006889 TI - [Not Available]. PMID- 21006890 TI - [Not Available]. PMID- 21006891 TI - [Not Available]. PMID- 21006893 TI - [Not Available]. PMID- 21006892 TI - [Not Available]. PMID- 21006894 TI - [Not Available]. PMID- 21006895 TI - [Not Available]. PMID- 21006896 TI - [Not Available]. PMID- 21006897 TI - [Not Available]. PMID- 21006898 TI - [Not Available]. PMID- 21006899 TI - [Not Available]. PMID- 21006900 TI - [Not Available]. PMID- 21006901 TI - [Not Available]. PMID- 21006902 TI - [Not Available]. PMID- 21006903 TI - [Not Available]. PMID- 21006904 TI - [Not Available]. PMID- 21006905 TI - [Not Available]. PMID- 21006906 TI - [Not Available]. PMID- 21006907 TI - [Not Available]. PMID- 21006908 TI - [Not Available]. PMID- 21006909 TI - [Not Available]. PMID- 21006910 TI - [Not Available]. PMID- 21006911 TI - [Not Available]. PMID- 21006912 TI - [Not Available]. PMID- 21006913 TI - [Not Available]. PMID- 21006914 TI - [Not Available]. PMID- 21006915 TI - [Not Available]. PMID- 21006916 TI - [Not Available]. PMID- 21006918 TI - [Not Available]. PMID- 21006917 TI - [Not Available]. PMID- 21006919 TI - The nature of fibrositis; the myalgic lesion and its secondary effects; a reflex theory. PMID- 21006920 TI - A study of rheumatism in a group of soldiers with reference to the incidence of trigger points and fibrositic nodules. PMID- 21006921 TI - Observations on the treatment of rheumatic fever with vitamin P. PMID- 21006922 TI - A benign type of rheumatic fever. PMID- 21006923 TI - Rheumatism in Sweden. PMID- 21006924 TI - CHRONIC rheumatism in Scotland. PMID- 21006925 TI - Isolation of the acid-soluble nucleotides of liver. PMID- 21006926 TI - The distribution of acid-soluble nucleotides in the livers of rats, fed and fasting. PMID- 21006927 TI - On the activation of fatty acid oxidation. PMID- 21006928 TI - Effect of nicotinic acid amide and sodium on glycolysis and oxygen uptake in brain homogenates. PMID- 21006929 TI - The influence of age and diet on the lipid composition of the rat. PMID- 21006930 TI - The effect of growth on the lipid composition of rat tissues. PMID- 21006931 TI - Preparation, properties, and parenteral administration of tryptophane-containing acid hydrolysates of proteins. PMID- 21006932 TI - A colorimetric determination of blood acetoin. PMID- 21006933 TI - The metabolism of acetaldehyde. PMID- 21006934 TI - The biological activity of pantolactone and pantoic acid. PMID- 21006935 TI - Determination of the degree of hydrolysis of partial acid hydrolysates of casein and fibrin. PMID- 21006936 TI - The isolation of alpha-glycerylphosphorylcholine from incubated beef pancreas; its significance for the intermediary metabolism of lecithin. PMID- 21006937 TI - The structural specificity of sulfanilamide-like compounds as inhibitors of the invitro conversion of inorganic iodide to thyroxine and diiodotyrosine by thyroid tissue. PMID- 21006938 TI - The regeneration of liver protein in the rat. PMID- 21006939 TI - Transaminases. PMID- 21006940 TI - Isolation of l-amino acid oxidase. PMID- 21006941 TI - Examination of l-amino acid oxidase by electrophoresis and the ultracentrifuge. PMID- 21006942 TI - The quantitative determination of thryoxine in iodinated casein having thyroidal activity. PMID- 21006943 TI - The effect of manganese compounds and certain other factors on the formation of thyroxine in iodinated casein. PMID- 21006944 TI - A direct method for determination of oxygen and carbon dioxide tensions in blood. PMID- 21006945 TI - The proteolytic inhibiting substance in the extract from unheated soy bean meal and its effect upon growth in chicks. PMID- 21006946 TI - Investigations of amino acids, peptides, and proteins; the determination of phenylalanine in protein hydrolysates with Leuconostoc mesenteroides P-60 and Lactobacillus casei. PMID- 21006947 TI - Investigations of amino acids, peptides, and proteins; the amino acid requirements of Lactobacillus fermenti 36. PMID- 21006948 TI - Investigations of amino acids, peptides, and proteins; the determination of histidine in protein hydrolysates with Lactobacillus fermenti 36. PMID- 21006949 TI - The determination of creatine and creatinine. PMID- 21006950 TI - The determination of catechol, phenol, and hydroquinone in urine. PMID- 21006951 TI - Constituents of the blood of the hibernating and normal rattlesnake, Crotalus horridus. PMID- 21006952 TI - The effect of phosphate on the solubility of calcium carbonate and of bicarbonate on the solubility of calcium and magnesium phosphates. PMID- 21006953 TI - The microbiological determination of amino acids in animal proteins. PMID- 21006954 TI - Microbiological determination of free leucine, isoleucine, valine, and threonine in dog plasma. PMID- 21006955 TI - Fate of ingested sulfide sulfur labeled with radioactive sulfur in the rat. PMID- 21006956 TI - On the electrophoretic pattern of red blood cell proteins. PMID- 21006957 TI - Itatartaric acid, a metabolic product of an ultravioletinduced mutant of Aspergillus terreus. PMID- 21006958 TI - Some properties of synthetic codecarboxylase. PMID- 21006959 TI - Intermediates of acetate oxidation in kidney. PMID- 21006960 TI - A nutritionally produced cerebellar disorder in chicks, not associated with E avitaminosis. PMID- 21006961 TI - Influence of gelatin and tryptophane on nicotinic acid requirement of chicks. PMID- 21006962 TI - Modifications in the Acetobacter suboxydane assay for p-aminobenzoic acid. PMID- 21006963 TI - Monolayers of oxidized and heat-bodied linseed oil. PMID- 21006964 TI - The effect of sodium silicates on iron oxide surfaces. PMID- 21006965 TI - Influence of method of deesterification on the viscosity and acid behavior of pectinic acid solutions. PMID- 21006967 TI - Correlation of viscosities of liquids with temperatures. PMID- 21006966 TI - Kinetics of deesterification of pectin. PMID- 21006968 TI - The depolarization of light scattered from polymer solutions. PMID- 21006969 TI - The thermal decomposition of ethylene iodide catalyzed by iodide ions. PMID- 21006970 TI - Radio-frequency dielectric properties of dehydrated carrots; application to moisture determination by electrical methods. PMID- 21006972 TI - Analysis of essential oils with the aid of refractive dispersion. PMID- 21006971 TI - Furfural; assets from a liability. PMID- 21006973 TI - Microbiological methods of analysis. PMID- 21006974 TI - PHENOL disinfectants. PMID- 21006975 TI - The control of pain. PMID- 21006976 TI - CROTONIC ACID and its esters. PMID- 21006977 TI - The broken mandibular needle. PMID- 21006978 TI - The treatment of Vincent's infection with penicillin. PMID- 21006979 TI - A microhardness instrument for studying surface hardness. PMID- 21006981 TI - Reproducing the natural teeth in acrylic resin. PMID- 21006980 TI - The link between ear, nose and throat surgery and dental conditions. PMID- 21006982 TI - How to get the best out of your materials. PMID- 21006983 TI - The practical application of acrylic material in conservative dentistry. PMID- 21006984 TI - The use of cheek wires in the treatment of fractures of the maxilla. PMID- 21006985 TI - A surgical classification of the malerupted mandibular third molar. PMID- 21006986 TI - Eruption of lower second premolar in spite of retained second deciduous molar. PMID- 21006987 TI - Report from a maxillo-facial centre at a Royal Air Force casualty clearing station in England. PMID- 21006988 TI - Speech problems and their dental significance. PMID- 21006989 TI - Nutrition in dentistry. PMID- 21006990 TI - Local anesthesia in dentistry. PMID- 21006991 TI - Vincent's stomatitis; a report based on the personal treatment of 175 cases in Army camps. PMID- 21006992 TI - ORAL manifestations of systemic disorders. PMID- 21006993 TI - Definite protection of cavities and abutment preparations, with low-fusing metal copings and splints used as temporary restorations. PMID- 21006994 TI - Construction of an acrylic resin dowel crown to be used as an abutment for a fixed bridge. PMID- 21006995 TI - Protection for the teeth through the teen-age growth period. PMID- 21006996 TI - Freak impacted lower third molar. PMID- 21006997 TI - Jaw fractures of common occurrence. PMID- 21006998 TI - Correct jaw relationship for full dentures; Pletcher-Durham technic. PMID- 21007000 TI - Extraction in orthodontia; a tragic failure in many cases. PMID- 21006999 TI - Hypodermic needles for local anesthesia of the mouth and jaws. PMID- 21007001 TI - Maintenance of natural conditions by intermittent pressure supplied by movable removable bridgework. PMID- 21007002 TI - Physiologic tooth and tissue stimulation made possible with precision attachment bridgework. PMID- 21007003 TI - The value of functional movement in precision attachment bridgework. PMID- 21007004 TI - The use of acrylic resin jacket crowns as abutments for precision attachment bridgework. PMID- 21007005 TI - Tissue tolerance in precision bridgework; mucosa, periosteum and bone involved. PMID- 21007006 TI - Esthetics in precision bridgework made possible through use of acrylic resin. PMID- 21007007 TI - Protection of abutment teeth by the use of precision attachments. PMID- 21007008 TI - Acrylic resin removable bridgework, employing precision attachments for retention. PMID- 21007009 TI - Operative and laboratory technics for constructing functional precision bridgework. PMID- 21007010 TI - An application of the mucostatic principle to the precision attachment partial denture. PMID- 21007011 TI - Adaptability of acrylic resin for ponties and copings. PMID- 21007012 TI - Precision bridges for unusual cases; patients saved from necessity for full dentures. PMID- 21007013 TI - Stress breaking; effects of buccolingual attachments on removable partial dentures. PMID- 21007014 TI - Operative procedure for gold inlays. PMID- 21007015 TI - Penicillin; its use for the treatment of Vincent's infection. PMID- 21007016 TI - The Manitoba Medical Service. PMID- 21007017 TI - Acrylique. PMID- 21007018 TI - Economic considerations in reestablishing a dental practice. PMID- 21007019 TI - President's message; when the dental officer returns. PMID- 21007020 TI - Educational opportunities for the returning veteran. PMID- 21007021 TI - Dental manpower of Minnesota in the postwar period. PMID- 21007022 TI - DENTAL materials in wartime. PMID- 21007023 TI - CHANGES in drugs, chemicals and devices during the war period. PMID- 21007024 TI - OPPORTUNITIES in the U.S. Public Health Service, Veterans Administration and Army and Navy Dental Corps. PMID- 21007025 TI - Opportunities for dental officers in education and research. PMID- 21007026 TI - Industrial dentistry as a career. PMID- 21007027 TI - Who should enter dental school? PMID- 21007028 TI - Wartime legislation. PMID- 21007029 TI - Roetgenographic examination of children. PMID- 21007030 TI - First permanent molar of the child. PMID- 21007031 TI - Preventive orthodontics. PMID- 21007032 TI - Oral diseases in children. PMID- 21007033 TI - Dentistry faces political action. PMID- 21007034 TI - Pityriasis rubra pilaris and vitamin A. PMID- 21007035 TI - Constituents of crude carotene of carrots. PMID- 21007036 TI - Magnesium content of meats. PMID- 21007037 TI - Blanching of vegetables for freezing; effect of different types of potable water on nutrients of peas and snap beans. PMID- 21007038 TI - Nutritive value of canned foods; effect of commercial canning and short-time storage on ascorbic acid content of grapefruit juice. PMID- 21007039 TI - Observations on thiamin content of stored wheat. PMID- 21007040 TI - Ascorbic acid, carotene, chlorophyll, riboflavin, and water content of summer squashes. PMID- 21007041 TI - Comparative tenderness of representative beef muscles. PMID- 21007042 TI - Effect of steam and hot-water blanching on ascorbic acid content of snap beans and cauliflower. PMID- 21007043 TI - Influence of chemical characteristics of soil on production of carotene in leaves of oats. PMID- 21007044 TI - Influence of chemical characteristics of soil on production of vitamin C in leaves of oats. PMID- 21007045 TI - A nomogram for the preparation of insulin-protamine zinc insulin mixtures. PMID- 21007046 TI - Metabolic abnormalities in obesity: a statistical survey. PMID- 21007047 TI - Effect of temperature on the experimental production of ulcers in the intestines of dogs. PMID- 21007048 TI - The inhibitory effect of mineral oil on the experimental production of ulcers. PMID- 21007049 TI - The importance of paracolon organisms with Salmonella and Shigella antigens. PMID- 21007050 TI - Staphylococci in gastroenterology. PMID- 21007051 TI - Infectious hepatitis with special reference to its occurrence in wounded men. PMID- 21007052 TI - The small intestine; a review of recent literature. PMID- 21007053 TI - Chronic ulcerative colitis with infantilism and carcinoma of the colon. PMID- 21007054 TI - Stoppage of bodily growth in a boy with stenosing enteritis. PMID- 21007055 TI - Observations on anorexia. PMID- 21007057 TI - Gastric acidity in rheumatoid arthritis. PMID- 21007056 TI - Cardio-esophageal relaxation. PMID- 21007059 TI - So-called fever or brucellosis in nervous persons. PMID- 21007058 TI - Experimental studies on the excretion of neutral red by the stomach. PMID- 21007060 TI - Some historical highlights in the development of clinical thermometry. PMID- 21007061 TI - What is the normal body temperature? PMID- 21007062 TI - The American Journal of Obstetrics and Gynecology 1920-1945. PMID- 21007063 TI - The pathogenesis of postsalpingectomy endometriosis in laparotomy scars. PMID- 21007064 TI - Therapeutic aspects of uterotubal insufflation in sterility. PMID- 21007065 TI - Sweet gland tumors of the vulva, benign (hidradenoma) and malignant (adenocarcinoma). PMID- 21007066 TI - Ten years of cesarean section at the Boston Lying-in Hospital. PMID- 21007067 TI - A review of the problem of cancer of the cervix since the use of radium in 1912. PMID- 21007068 TI - The curability of granulosa-cell tumors. PMID- 21007069 TI - Diet regulation and controlled weight in pregnancy. PMID- 21007070 TI - Government and maternal welfare. PMID- 21007071 TI - The Rh factor in obstetrics. PMID- 21007072 TI - The surgical correction of congenital aplasia of the vagina. PMID- 21007073 TI - Hypertrophy of the uterus. PMID- 21007074 TI - Aneurysm of the splenic artery with rupture, a rare complication of pregnancy. PMID- 21007075 TI - The search for the female sex hormones. PMID- 21007076 TI - The role of Porro cesarean section in modern obstetrics. PMID- 21007078 TI - Investigation of childlessness. PMID- 21007077 TI - Ectopic gestation; the diagnostic value of cul-de-sac aspiration. PMID- 21007079 TI - Baryta. PMID- 21007080 TI - Short proving of iridium chloride. PMID- 21007081 TI - Homoeopathic therapy in some nerve diseases. PMID- 21007082 TI - Homeopathy and surgery. PMID- 21007083 TI - Catharrhal jaundice; report of a case. PMID- 21007084 TI - Homeopathic authors. PMID- 21007085 TI - Sulphur from another angle. PMID- 21007086 TI - Basic urology. PMID- 21007087 TI - The shell-pad-strap method of fitting, and the fabrication of, flexible appliances. PMID- 21007088 TI - The Polokoff pad. PMID- 21007089 TI - Coordination; report on Salem Hospital's growth as a center of area-wide service. PMID- 21007090 TI - Lengthening shadow of the hospital pharmacist. PMID- 21007091 TI - BARBWIRE hospital; how six medical officers fought Germany behind the German line. PMID- 21007092 TI - In the wisely planned utility building, the value is multiplied. PMID- 21007094 TI - President Truman's message on the National health program. PMID- 21007093 TI - How Arkansas hospitals and health department built a program for care of the indigent. PMID- 21007095 TI - The National Health Act of 1945. PMID- 21007096 TI - The consideration and evaluation of perquisites in determining the wage and salary scale of hospital staff members and personnel. PMID- 21007097 TI - The Hospital Construction Act (S.191). PMID- 21007098 TI - Food-poisoning staphylococci and the order of their resistance to penicillin; inhibition of coagulase production. PMID- 21007099 TI - Production of Clostridium perfringens alpha toxin. PMID- 21007100 TI - Anaphylactic properties of photo-oxidized rabbit-antisera (VS sheep erythrocytes and pneumococci) and horse-antiserum (VS diphtherial toxin) containing univalent antibodies. PMID- 21007101 TI - Protective value of univalent antibodies produced by photo-oxidation of antipneumococcal rabbit-serum and antidiphtheric horse-serum. PMID- 21007102 TI - The determination of meningococcic antibodies by a centrifuge-agglutination test. PMID- 21007103 TI - The role of ether anesthesia in the production of influenza virus pneumonia in mice. PMID- 21007104 TI - An electrophoretic study of an anti-influenzal horse serum. PMID- 21007105 TI - Serologic studies in typhus-vaccinated individuals; the effect of a stimulating dose of typhus vaccine on the Weil-Felix and complement-fixing antibodies. PMID- 21007106 TI - [Not Available]. PMID- 21007107 TI - [Not Available]. PMID- 21007108 TI - [Not Available]. PMID- 21007109 TI - [Not Available]. PMID- 21007110 TI - [Not Available]. PMID- 21007111 TI - [Not Available]. PMID- 21007112 TI - [Not Available]. PMID- 21007113 TI - [Not Available]. PMID- 21007115 TI - [Not Available]. PMID- 21007114 TI - [Not Available]. PMID- 21007116 TI - Patients and prejudice; lay attitudes toward women physicians. PMID- 21007117 TI - Antipathy and social behavior. PMID- 21007118 TI - Studies of the effects of ammonium picrate on man and certain experimental animals. PMID- 21007119 TI - Observations on the Fujiwara reaction as a test for chlorinated hydrocarbons. PMID- 21007120 TI - Animal studies on the toxicity of inhaled antimony trioxide. PMID- 21007121 TI - Observations on the effects of gamma-valero-lactone upon experimental animals. PMID- 21007122 TI - Calcium cyanide gas for animal experiments. PMID- 21007123 TI - POSTWAR outlook for physicians. PMID- 21007124 TI - Significance of some of the fundamental physical findings in examination of the heart. PMID- 21007125 TI - Continuous caudal obstetrical analgesia. PMID- 21007126 TI - Rh hazards in general practice. PMID- 21007127 TI - [Not Available]. PMID- 21007128 TI - [Not Available]. PMID- 21007129 TI - [The problem of the biological nature of the viruses]. PMID- 21007130 TI - [Stimulation of the growth of microbes of the intestinal group]. PMID- 21007131 TI - [On the functional role of the chondriosomic apparatus of a cell]. PMID- 21007132 TI - [The effect of various metals on the conjunctive elements of mammalian liver; first communication]. PMID- 21007133 TI - [Histological observations of the transplanted epichondrion]. PMID- 21007134 TI - [Ectoplasmatic process of formation of collageneous fibres in the histogenesis of the smooth muscles of the amnion of the chick embryo]. PMID- 21007135 TI - [On the structures formed in the elements of white blood in supravital staining]. PMID- 21007136 TI - [Subvital congo red testing]. PMID- 21007137 TI - [Glycogen loading of the interneuron synapsis and its functional sequels; the morphology of glycogen distribution and transmutation]. PMID- 21007138 TI - [Blood changes in traumatic shock of war]. PMID- 21007139 TI - [Intra vitam washing of the organism with homologous blood associated with full substitution of the recipient's blood by that of a donor]. PMID- 21007140 TI - [The role of diet in the morphological deformations of the intestinal wall in experimental mechanical ileus in dogs]. PMID- 21007141 TI - [On the absorptive function of the membrana mucosa of the mouth]. PMID- 21007142 TI - [Secretory activity of the stomach in dogs during stay on Mt. Elbruz]. PMID- 21007143 TI - [Evolution of the structure and function of the stomach and pancreas with respect to age]. PMID- 21007144 TI - [The influence of ions in formation of vitamins in the yeast cell]. PMID- 21007145 TI - [Ions as a receptor irritator]. PMID- 21007146 TI - [Activity of carbohydrase in disturbances of the acidoalkaline balance in the organism]. PMID- 21007147 TI - [Electro-encephalography in trauma of the brain]. PMID- 21007148 TI - [Electroencephalographic examination in air contusion]. PMID- 21007149 TI - [The currents of muscle action in damages of the nerve trunks]. PMID- 21007150 TI - [The character of electric potentials of the glossopharyngeal nerve in taste irritation of the tongue]. PMID- 21007152 TI - [On the dependence of the sexual reflexes of the skeleton muscles on irritation of the glandulae glomiformae]. PMID- 21007151 TI - [Chronaxometric investigations in gunshot wounds of the median nerve]. PMID- 21007153 TI - The in-vitro sensitivity of H. influenzae to penicillin, with special reference to meningeal strains of Pittman's Type b. PMID- 21007154 TI - Meningitis due to a penicillin- and sulphonamide-sensitive Pittman b strain of H. influenzae; recovery. PMID- 21007155 TI - Repatriation; a psychiatric study of 100 naval ex-prisoners of war. PMID- 21007156 TI - Sixth-nerve paralysis after spinal analgesia. PMID- 21007157 TI - Typhoid fever complicated by benign tertian malaria. PMID- 21007158 TI - Neurological complications in cerebrospinal meningitis treated with penicillin. PMID- 21007159 TI - Myxoedema induced by thiouracil. PMID- 21007160 TI - Impressions of surgery in West Africa. PMID- 21007161 TI - Protein metabolism. PMID- 21007162 TI - Treatment of varicose ulcers. PMID- 21007163 TI - Morphine as a prophylactic for ileus. PMID- 21007165 TI - Significance of the E.S.R. PMID- 21007164 TI - Non-specific mesenteric lymphadenitis. PMID- 21007166 TI - PROPOSED national health service; fundamental principles of the medical profession. PMID- 21007167 TI - Survey of fracture treatment. PMID- 21007168 TI - Nutrition in Vienna in September, 1945. PMID- 21007169 TI - Toxic effects of 2,2-bis (p-chlorphenyl) l,l,l-trichlorethane (D.D.T.) in man. PMID- 21007170 TI - A fatal case of D.D.T. poisoning in a child, with an account of two accidental deaths in dogs. PMID- 21007171 TI - Observations on keratoconjunctivitis (cases seen in military hospitals). PMID- 21007172 TI - A case of tick typhus in the Sudan. PMID- 21007173 TI - Administration of penicillin by intramuscular drip. PMID- 21007174 TI - STETHOSCOPE versus x rays. PMID- 21007175 TI - Descent of the testis. PMID- 21007176 TI - Non-specific mesenteric lymphadenitis. PMID- 21007177 TI - Volvulus of small intestine. PMID- 21007178 TI - Prostatic obstruction. PMID- 21007179 TI - B.L.A. medicine. PMID- 21007180 TI - Estimation of serum proteins by the Linderstrom-Lang gradient. PMID- 21007181 TI - Liver function in infective hepatitis gauged by hippuric acid synthesis tests. PMID- 21007182 TI - Management of recent fracture-dislocations of the cervical spine. PMID- 21007183 TI - The therapeutic efficiency of ultra-violet-light apparatus; a comparison of tests. PMID- 21007184 TI - Anti-M iso-agglutinins in human serum. PMID- 21007185 TI - Treatment of chilblains by paravertebral sympathetic block. PMID- 21007186 TI - Duodenal atresia in a newborn infant. PMID- 21007188 TI - Contributions of the war effort to medicine. PMID- 21007187 TI - Losses of Polish medicine. PMID- 21007189 TI - Modern concepts of war neuroses. PMID- 21007190 TI - What can the practitioner do in treating the neuroses? PMID- 21007191 TI - Evaluation of early postoperative activity. PMID- 21007192 TI - Psychopathic personality; the use of this term in the Canadian Army overseas. PMID- 21007193 TI - The transplantation of skin. PMID- 21007194 TI - Fungous infections of the skin. PMID- 21007196 TI - CHRYSANTHEMUMS vs. malaria. PMID- 21007195 TI - Menstruation and its disorders. PMID- 21007197 TI - Observations on the treatment of infantile paralysis in the acute stage. PMID- 21007198 TI - Bronchoscopy in the treatment of pulmonary atelectasis. PMID- 21007199 TI - Visual signs in diagnosis. PMID- 21007200 TI - Results of a random chest x-ray survey of healthy troops in Canada. PMID- 21007201 TI - Forward abdominal surgery; an analysis of 230 cases. PMID- 21007202 TI - Treatment of obesity by appetite-depressing drugs. PMID- 21007204 TI - Anatomical clinics. PMID- 21007203 TI - A study of causes of blindness in over 12,000 cases in Canada. PMID- 21007205 TI - Benzyl-benzoate and wool dermatitis. PMID- 21007206 TI - [Not Available]. PMID- 21007207 TI - Metastatic carcinoma of the choroid. PMID- 21007208 TI - A simple method for spinal anesthesia in anorectal surgery. PMID- 21007209 TI - An evaluation of roentgen pelvimetry. PMID- 21007210 TI - Phimosis from the flesh fly, Wohlfahrtia vigil. PMID- 21007211 TI - Religion and medicine. PMID- 21007212 TI - Nasotracheal anaesthesia for tonsillectomy and teeth extraction. PMID- 21007213 TI - Wilhelm Conrad Rontgen (1845-1923) and the early development of radiology. PMID- 21007214 TI - Clinical and epidemiologic notes on undulant fever (brucellosis). PMID- 21007215 TI - The treatment of weak, painful feet. PMID- 21007216 TI - Adrenal disease. PMID- 21007217 TI - The diagnosis of nephritis. PMID- 21007218 TI - PERITONEOSCOPY. PMID- 21007219 TI - Rheumatic fever; etiology, epidemiology, prevalence. PMID- 21007220 TI - A case of extreme mediastinal dislocation complicating tuberculosis. PMID- 21007221 TI - The deficiency pattern of the small bowel. PMID- 21007222 TI - The presence of copper and lead in some human tissues. PMID- 21007223 TI - NEUROGENIC bladder. PMID- 21007224 TI - Cerebral malaria. PMID- 21007226 TI - Tularemic pneumonia; report of case. PMID- 21007225 TI - Silico-tuberculosis. PMID- 21007227 TI - [Not Available]. PMID- 21007228 TI - [Not Available]. PMID- 21007229 TI - [Not Available]. PMID- 21007230 TI - [Not Available]. PMID- 21007231 TI - [Not Available]. PMID- 21007232 TI - [Not Available]. PMID- 21007233 TI - Posterior gastroenterostomy for infantile pyloric stenosis. PMID- 21007234 TI - Colles fracture; a review of treatment. PMID- 21007235 TI - Neurofibroma of the bladder; report of a case. PMID- 21007236 TI - Rupture of a dissecting aortic aneurysm; report of a fatal case. PMID- 21007237 TI - Human brucellosis. PMID- 21007238 TI - Melanocarcinoma of the vagina; a case report. PMID- 21007239 TI - Allergic rhinitis. PMID- 21007240 TI - Fractures of the neck of the femur. PMID- 21007241 TI - Plastic procedures about the eyes. PMID- 21007242 TI - Indications and contraindications to gastroscopy. PMID- 21007243 TI - Orbital proptosis. PMID- 21007244 TI - Emotional control a factor in preserving the integrity of the heart. PMID- 21007245 TI - The Rorschach test in postencephalitis. PMID- 21007247 TI - The Illinois Hospital Survey. PMID- 21007246 TI - Hemorrhagic ancephalopathy following five day treatment of early syphilis with massive doses of mapharsen; report of a case with recovery. PMID- 21007248 TI - Uncommon etiological factors in pathological conditions of the gall-bladder. PMID- 21007249 TI - Occurrence of fluorosis in endemic forms in Hyderabad state. PMID- 21007250 TI - Leptospirosis without jaundice. PMID- 21007251 TI - The occurrence of leptospirosis in Orissa. PMID- 21007252 TI - The unsuitability of white mice for studies of leptospirosis. PMID- 21007253 TI - Sulphapyridine in gonorrhoea. PMID- 21007254 TI - Bronchial asthma and pulmonary tuberculosis. PMID- 21007255 TI - An easy method of producing permanent rough variation in cholera vibrios. PMID- 21007256 TI - Turmeric and vegetable oils as repellents against anopheline mosquitoes. PMID- 21007257 TI - Tropical ulcer; a study of one hundred cases collected in the city of Madras. PMID- 21007258 TI - Application of the D.E.C. medium to the isolation of typhoid bacilli from sewage in Calcutta. PMID- 21007259 TI - Rapid method of paraffin embedding. PMID- 21007260 TI - Blood-pressure variation and cardiovascular changes in diabetes mellitus. PMID- 21007261 TI - Myotonia congenita (Thomsen's disease). PMID- 21007262 TI - Congenital heart disease in a case of resistant kala-azar with pulmonary tuberculosis. PMID- 21007263 TI - The use of the femoral vein for venoclysis. PMID- 21007264 TI - Hepatic amoebiasis. PMID- 21007265 TI - Does sulphapyridine really delay resolution in pneumonia. PMID- 21007266 TI - Clinical observations on penicillin. PMID- 21007268 TI - DIAGNOSIS of kala-azar febrile and afebrile cases. PMID- 21007267 TI - Minimal lesion in pulmonary tuberculosis; how to make it out and to treat it to prevent its break-down. PMID- 21007269 TI - The liver. PMID- 21007270 TI - Tachycardia and its treatment. PMID- 21007271 TI - The responsibility of the private physician in tuberculosis control. PMID- 21007272 TI - The etiology of Colorado tick fever. PMID- 21007273 TI - The preparation of highly purified PRS influenza virus from infected mouse lungs. PMID- 21007274 TI - Studies on pneumonia virus of mice (PVM); the precision of measurements in vivo of the virus and antibodies against it. PMID- 21007275 TI - Studies on pneumonia virus of mice (PVM); immunological evidence of latent infection with the virus in numerous mammalian species. PMID- 21007276 TI - Studies on the nature of resistance of gram-negative bacilli to penicillin; antagonistic and enhancing effects of amino acids. PMID- 21007277 TI - Dicumarol therapy in acute coronary thombosis; results in fifty attacks; with review of data on embolic complications and immediate mortality in myocardial infarction. PMID- 21007278 TI - Rehabilitation of the warworn civilian. PMID- 21007279 TI - Loeffler's syndrome. PMID- 21007280 TI - The medical profession today and tomorrow. PMID- 21007281 TI - The general treatment of arthritis. PMID- 21007282 TI - Bronchiectasis. PMID- 21007283 TI - Pseudomyxoma peritonaei in a man following rupture of a retrocecal mucocele. PMID- 21007284 TI - Artificially-induced remission in a case of subacute bacterial endocarditis. PMID- 21007285 TI - Postmortem examinations. PMID- 21007286 TI - Surgical shock; an experimental study of its aetiology. PMID- 21007287 TI - Sulphathiazole and sulphaguanidine in the treatment of bacillary dysentery. PMID- 21007288 TI - Ten year planning in tuberculosis; with special reference to Mysore. PMID- 21007289 TI - So-called tropical ulcer in Angul. PMID- 21007290 TI - Medical education. PMID- 21007291 TI - Atypical meningococcal meningitis. PMID- 21007292 TI - DEATH and disease in the Bengal famine. PMID- 21007293 TI - A comparison of the results obtained with the Hanger caphalin-cholesterol flocculation test and the Maclagan thymol turbidity test in patients with liver disease. PMID- 21007294 TI - Antigenic properties of various lipoids from beef heart. PMID- 21007295 TI - A study of the relative sensitivity of different lots of antigen employed in the serologic tests for syphilis. PMID- 21007296 TI - Theory of the colloidal gold reaction; reactions between gold sol and isolated protein fractions. PMID- 21007297 TI - Experimental production of pulmonary embolism by the use of a venous catheter. PMID- 21007298 TI - Penicillin combined with fever therapy; a preliminary report of twenty cases of early syphilis. PMID- 21007299 TI - Penicillin therapy in human bartonellosis (Carrion's disease). PMID- 21007300 TI - A standardised back burn procedure for the white rat suitable for the study of the effects of therapeutic and toxic agents on long-term survival. PMID- 21007301 TI - Hydrolyzed casein (capain) as a plasma substitute. PMID- 21007302 TI - Studies on hypertension; effect of high spinal anesthesia on the blood pressure of patients with hypertension and far-advanced renal disease; its possible relationship to the pathogenesis of hypertension. PMID- 21007303 TI - The effect of intravenous typhoid vaccine on the intravenous glucose tolerance test. PMID- 21007304 TI - The diagnosis of enterobiasis; comparative study of the Graham and Hall techniques in the diagnoses of enterobiasis. PMID- 21007305 TI - The urinary excretion of antipernicious anemia factor. PMID- 21007306 TI - The activity of synthetic Lactobacillus casei factor (folic acid) as an antipernicious anemia substance; observations on four patients; two with Addisonian pernicious anemia, one with montropical sprue and one with pernicious anemia of pregnancy. PMID- 21007307 TI - A note on gastric retention in one-hour, two-dose glucose tolerance tests. PMID- 21007308 TI - Photoelectric determination of blood thiocyanates without precipitation of proteins. PMID- 21007309 TI - A colorimetric determination of paraldehyde. PMID- 21007310 TI - The J.S.B. stain for blood parasites. PMID- 21007311 TI - Nutritional recovery following removal of all but three feet of jejunum and half of the colon. PMID- 21007312 TI - Malignant melanoma case report. PMID- 21007313 TI - Agnogenic myeloid metaplasia involving the bone marrow, liver, spleen and lymph nodes case report. PMID- 21007314 TI - What the general practitioner should know about leprosy. PMID- 21007316 TI - Penicillin in the treatment of gonorrhea. PMID- 21007315 TI - Operative management of ingrown toenail. PMID- 21007317 TI - The diagnosis of thromboangiitis obliterans and peripheral arteriosclerosis. PMID- 21007318 TI - Polyradiculoneuritis case report. PMID- 21007319 TI - For acquired hemolytic icterus nontraumatic emergency splenectomy. PMID- 21007320 TI - Amyloid disease of the kidney. PMID- 21007321 TI - Blastomycosis involving the lungs, adrenals, kidneys, periprostatic tissue, right epididymis, testicle and vas deferens and seminal vesicles; case report. PMID- 21007322 TI - Missouri medicine aims rehabilitation of indigent physically impaired. PMID- 21007323 TI - Clinical experiences with thiouracil. PMID- 21007324 TI - Relapsing febrile nodular nonsuppurative panniculitis; with a report of a case. PMID- 21007325 TI - The high frequency currents in surgery. PMID- 21007326 TI - Fibrosis of the pancreatic ducts case report. PMID- 21007327 TI - Diseases of the bile duct. PMID- 21007328 TI - Carcinoma of the prostate gland, and benefits of diethylstilbestrol or orchiectomy. PMID- 21007329 TI - The Barnard Free Skin and Cancer Hospital; research report for 1944. PMID- 21007331 TI - Enrichment of bread. PMID- 21007330 TI - Bronchoscopy; its role in the diagnosis and treatment of pulmonary tuberculosis. PMID- 21007332 TI - Thiouracil; its use in hyperthyroidism. PMID- 21007333 TI - The patient diagnoses the doctor. PMID- 21007334 TI - Intestinal obstruction; two cases of unusual etiology. PMID- 21007335 TI - Continuous drip pentothal sodium with supplementary anesthesia. PMID- 21007336 TI - Industrial health; recent developments in pneumoconiosis. PMID- 21007337 TI - Tuberculosis in industry. PMID- 21007339 TI - Pneumatic rupture of the colon. PMID- 21007338 TI - Occupational dermatoses. PMID- 21007340 TI - Environmental control of occupational disease. PMID- 21007341 TI - General program of the industrial hygiene services in Missouri. PMID- 21007342 TI - Industrial health activities in St. Louis. PMID- 21007343 TI - The surgical care of the operable malignant lesions of the stomach. PMID- 21007344 TI - Chemotherapeutic and surgical treatment of acute osteomelitis. PMID- 21007345 TI - [Not Available]. PMID- 21007346 TI - [Not Available]. PMID- 21007347 TI - Retropubic prostatectomy; a new extravesical technique; report of 20 cases. PMID- 21007348 TI - Ambulatory treatment of early syphilis with penicillin; rationale, experimental basis, and preliminary results. PMID- 21007349 TI - EFFECT of large doses of alkali on kidney function. PMID- 21007350 TI - Effect of penicillin on Bacillus proteus. PMID- 21007351 TI - Acute brachial radiculitis; course and prognosis. PMID- 21007352 TI - Extensive interstitial calcinosis, with osteoporesis and scleroderma dermatomyositis. PMID- 21007353 TI - ATYPICAL lichen planus and mepacrine. PMID- 21007354 TI - OCCUPATION at a glance. PMID- 21007355 TI - STAFFING of county hospitals. PMID- 21007356 TI - Normal life of the red cell. PMID- 21007357 TI - Hospital, industry, and the injured man; a surgeon's thoughts on rehabilitation. PMID- 21007358 TI - Resettlement of the disabled. PMID- 21007359 TI - Clinical value of muscle biopsies. PMID- 21007360 TI - Exposure of posterior horn of medial meniscus. PMID- 21007361 TI - Thrombocytopenic purpura with normal bleeding-time. PMID- 21007362 TI - Probable relapse of malignant tertian malaria after thirteen years. PMID- 21007363 TI - Orthopaedic treatment of ankylosing spondylitis. PMID- 21007364 TI - Louse-borne relapsing fever treated with calcium gold keratinate. PMID- 21007365 TI - Polyvinyl alcohol as a medium for local penicillin therapy. PMID- 21007366 TI - BOVINE infection and disease. PMID- 21007367 TI - Assessment of industrial disability. PMID- 21007368 TI - POST-WAR bread policy. PMID- 21007369 TI - Retropubic prostatectomy. PMID- 21007370 TI - Intestinal obstruction. PMID- 21007371 TI - A case of psychosomatic interest. PMID- 21007372 TI - Influenzal meningitis. PMID- 21007373 TI - German war surgery. PMID- 21007374 TI - Polycythemia vera. PMID- 21007375 TI - Perforated gallbladder; paralytic illus. PMID- 21007376 TI - Caricinoma of ovary in a child. PMID- 21007377 TI - Idiopathic methemoglobinemia. PMID- 21007378 TI - Giant cell tumor of the ulna with excision and reconstruction. PMID- 21007379 TI - DOCTORS and saints. PMID- 21007380 TI - The typical headache of essential hypertension. PMID- 21007381 TI - The surgical treatment of varicose veins; retrogade catheter method. PMID- 21007382 TI - A transverse incision for gallbladder surgery. PMID- 21007384 TI - Dysenteries. PMID- 21007383 TI - The causalgic state; early and fixed lesions. PMID- 21007385 TI - Eosinophilia and eosinophilic lungs. PMID- 21007386 TI - Effort syndrome. PMID- 21007387 TI - Treatment of thromboangitis obliterans. PMID- 21007388 TI - Practical hints for judging and treating acute comatose conditions. PMID- 21007389 TI - Vitamin therapy. PMID- 21007390 TI - Pantothenic acid in animal nutrition. PMID- 21007391 TI - Vitamins, their role in pregnancy. PMID- 21007392 TI - Cerebral injury by blunt mechanical trauma; review of literature. PMID- 21007393 TI - The absorption and elimination of gases of the body in relation to its fat and water content. PMID- 21007394 TI - Decompression sickness incident to deep sea diving and high altitude ascent. PMID- 21007395 TI - Circulation and respiration in fever. PMID- 21007396 TI - Radiology in the diagnosis of dyspepsia. PMID- 21007397 TI - Childbirth as an athletic feat. PMID- 21007398 TI - Second thoughts on soil fertility and dental caries. PMID- 21007399 TI - Suggestion in medicine. PMID- 21007400 TI - The diet of dyspeptics. PMID- 21007401 TI - The relation of septal deflections to rhinoplasty. PMID- 21007402 TI - Hemorrhoids associated with nervous indigestion. PMID- 21007403 TI - Penicillin instillations in chronic otitis media and sinus infections; clinical appraisal, preliminary report. PMID- 21007404 TI - Hiccup. PMID- 21007405 TI - Should ordinary hospitals be used as medical schools? PMID- 21007406 TI - [Physical methods of treatment of the disabled of the Patriotic War in the polyclinics and health stations]. PMID- 21007407 TI - [On medical prosthesis]. PMID- 21007408 TI - [Experience in a medico-evacuation service of a specialized hospital]. PMID- 21007409 TI - [The proper surgical treatment of small lesions]. PMID- 21007410 TI - [Adaptation of the regimen in educational work with delicate children in the nurseries]. PMID- 21007411 TI - [Dysentery in children and measures for its control in the health stations]. PMID- 21007412 TI - [The clinics and prophylaxis of congenital syphilis]. PMID- 21007413 TI - [The work of malaria control officials in the villages]. PMID- 21007414 TI - Rheumatic fever as a public health problem. PMID- 21007415 TI - Medical non-missionaries. PMID- 21007416 TI - Woman's Medical College of Pennsylvania, 1888-1900. PMID- 21007417 TI - Dawn brings new courage; in China, the story of a medical missionary. PMID- 21007419 TI - Modern trends in burn therapy as seen by the British. PMID- 21007418 TI - The work of an English cancer hospital during the war. PMID- 21007420 TI - The coming new order in medical practice. PMID- 21007421 TI - The problems of nursing in the rural hospital. PMID- 21007422 TI - Proper approach to geriatrics. PMID- 21007423 TI - Combined treatment in gonorrhea cases. PMID- 21007424 TI - GASTRIC mucosal atrophy and carcinoma of the stomach. PMID- 21007425 TI - The treatment of strabismus in children. PMID- 21007426 TI - Some conditions which may be confused with an anginal syndrome. PMID- 21007427 TI - Mediastinal cysts. PMID- 21007428 TI - The treatment of major burns in naval warfare. PMID- 21007429 TI - Penicillin aerosolization in the treatment of serious respiratory infections; a preliminary report. PMID- 21007430 TI - Clinical and laboratory studies of 91 workers with apical systolic murmurs. PMID- 21007431 TI - Serologic types of hemolytic streptococci in scarlet fever in Massachusetts. PMID- 21007432 TI - Hemoglobinemia and the hemoglobinurias. PMID- 21007433 TI - Acute hemorrhagic interstitial pneumonia. PMID- 21007434 TI - Glioblastoma multiforme of medulla. PMID- 21007435 TI - INFLUENZA. PMID- 21007436 TI - Primary anastomosis in carcinoma of the colon. PMID- 21007437 TI - Thiouracil as a cause of neutropenia and agranulocytosis. PMID- 21007439 TI - Menstruation, its disorders and their treatment. PMID- 21007438 TI - The clinical significance of data accumulated in the medical care of young women. PMID- 21007440 TI - Subacute and chronic glomerulonephritis developing in congenital polycystic kidneys. PMID- 21007441 TI - Acute pancreatitis, with fat necrosis. PMID- 21007442 TI - Toxoplasmic encephalitis; clinical findings in two patients from Pacific Northwest. PMID- 21007443 TI - Melanoma of small intestine. PMID- 21007444 TI - Typhus fever. PMID- 21007445 TI - Necessary cooperation of all physicians. PMID- 21007446 TI - Present and future prepayment plans. PMID- 21007447 TI - The Medical Service Bureau an answer to socialized medicine. PMID- 21007448 TI - Extraperitoneal cesarean section; with special reference to the Waters technic. PMID- 21007449 TI - Clinical study of 15 cases of sinusitis. PMID- 21007450 TI - Treatment of blood dyscrasias. PMID- 21007451 TI - Occurrence of Bacillus welchiigas gangrene at site of penicillin intramuscular clyses. PMID- 21007452 TI - The use of the mercurial diuretics. PMID- 21007453 TI - CARDIOLOGY. PMID- 21007454 TI - The treatment of simple and toxic enlargements of the thyroid gland. PMID- 21007455 TI - Discussion on so-called rheumatism. PMID- 21007456 TI - The significance of hoarseness. PMID- 21007457 TI - Shall we nationalize medicine? PMID- 21007458 TI - Experiences as an Army physician in Malta and Sicily. PMID- 21007459 TI - Transport of casualties by air. PMID- 21007460 TI - Social psychiatry in the post-war world. PMID- 21007461 TI - Discussion on the use and abuse of manipulative surgery. PMID- 21007462 TI - The beginnings or asepsis; the story of a tragic life. PMID- 21007463 TI - Necropsies in the hospitals of Chicago. PMID- 21007464 TI - Annual report of Section on Radium Therapy for 1944. PMID- 21007465 TI - Neurofibromatosis with sarcoma of leg; report of case. PMID- 21007466 TI - Notes on a modified open-circuit method for the measurement of residual air. PMID- 21007467 TI - The crying of newly born babies; the individual phase. PMID- 21007468 TI - Annual report of Gynecologic Surgery for 1944. PMID- 21007469 TI - The expanding field of physical medicine. PMID- 21007470 TI - Transthoracic resection of lesions of the lower portion of the esophagus and the cardia of the stomach. PMID- 21007471 TI - Report of genito-urinary surgery for 1944. PMID- 21007472 TI - Observations on certain rheological properties of human cervical secretion. PMID- 21007473 TI - Some new facts concerning the prognosis and treatment of carcinoma of cervix by radiation. PMID- 21007474 TI - Congenital defects following rubella in pregnancy. PMID- 21007475 TI - Notes on certain trends in public health work in the City of New York and in the States of New York, Massachusetts and Georgia. PMID- 21007476 TI - Some surgical aspects of urinary bilharziasis. PMID- 21007477 TI - International biological standards; prospect and retrospect. PMID- 21007478 TI - The diagnosis and primary surgical treatment of injuries of the hand. PMID- 21007480 TI - Penicillin treatment of early syphilis. PMID- 21007479 TI - Hormones in tuberculosis. PMID- 21007481 TI - FUTURE of industrial medicine in Rhode Island. PMID- 21007482 TI - The Rhode Island second injury fund. PMID- 21007483 TI - Sodium pentothal anesthesia. PMID- 21007484 TI - Skiodan as a contrast medium in utero-salpingography. PMID- 21007485 TI - Technical pitfalls in thyroid surgery. PMID- 21007486 TI - Clinical comparison of methergine and natural ergonovine. PMID- 21007487 TI - FAILURE OF vitamin K as an antidote in dicumarol poisoning. PMID- 21007488 TI - Prospect for the future control of tuberculosis. PMID- 21007489 TI - The forward surgery of abdominal war wounds. PMID- 21007490 TI - A common antigenic factor between B. typhosus and B. dysenteriae Flexner. PMID- 21007491 TI - Tuberculose: aphorismen en consequenties. PMID- 21007492 TI - Succulent collecting. PMID- 21007493 TI - The sickle-cell trait in the South African Bantu. PMID- 21007494 TI - [Not Available]. PMID- 21007495 TI - [Not Available]. PMID- 21007496 TI - [Not Available]. PMID- 21007498 TI - [Not Available]. PMID- 21007497 TI - [Not Available]. PMID- 21007499 TI - [Not Available]. PMID- 21007500 TI - [Not Available]. PMID- 21007501 TI - [Not Available]. PMID- 21007502 TI - [Not Available]. PMID- 21007504 TI - [Not Available]. PMID- 21007503 TI - [Not Available]. PMID- 21007505 TI - [Not Available]. PMID- 21007506 TI - [Not Available]. PMID- 21007507 TI - [Not Available]. PMID- 21007508 TI - [Not Available]. PMID- 21007509 TI - [Not Available]. PMID- 21007510 TI - [Not Available]. PMID- 21007511 TI - [Not Available]. PMID- 21007512 TI - [Not Available]. PMID- 21007513 TI - [Not Available]. PMID- 21007514 TI - [Not Available]. PMID- 21007515 TI - [Not Available]. PMID- 21007516 TI - [Not Available]. PMID- 21007517 TI - [Not Available]. PMID- 21007518 TI - [Not Available]. PMID- 21007519 TI - [Not Available]. PMID- 21007520 TI - [Not Available]. PMID- 21007521 TI - [Not Available]. PMID- 21007522 TI - [Not Available]. PMID- 21007523 TI - The mode of action of sulfonamides. PMID- 21007524 TI - Thiouracil: its present status in the treatment of hyperthyroidism. PMID- 21007525 TI - Early ambulation of the post-operative patient; a review of current literature. PMID- 21007526 TI - Fluid requirements of the surgical patient. PMID- 21007527 TI - [Not Available]. PMID- 21007528 TI - [Not Available]. PMID- 21007529 TI - [Not Available]. PMID- 21007530 TI - [Not Available]. PMID- 21007531 TI - Some strange tumors. PMID- 21007532 TI - Postoperative pneumonia and atelectasis. PMID- 21007533 TI - Neckel's diverticulum; fifty-six cases. PMID- 21007534 TI - The hyperpnea test for latent coronary artery disease; a preliminary report. PMID- 21007535 TI - The control of hemorrhage after tonsillectomy; the use of thrombin. PMID- 21007536 TI - Bacterial endocarditis and penicillin; report of two cases with diabetes. PMID- 21007537 TI - Penicillin in the treatment of meningitis. PMID- 21007538 TI - Treatment of pilonidal cysts. PMID- 21007539 TI - The role of demerol in obstetrics. PMID- 21007540 TI - Renal hypertension; nephrectomies at Wisconsin General Hospital. PMID- 21007541 TI - Streptococcus fecalis bacteremia and meningitis; report of a case cured with penicillin. PMID- 21007542 TI - The agglutination of staphylococcus aureus in the presence of normal or influenza virus-infected mouse lung filtrates and of chorio-allantoic fluids. PMID- 21007543 TI - The Sturge-Weber syndrome; report of three cases. PMID- 21007544 TI - On the development of the amnion and exoccelomic membrane in the previllous human ovum. PMID- 21007545 TI - On the relation between discharge zone and subliminal fringe in a motoneuron pool supplied by a homogeneous presynaptic pathway. PMID- 21007546 TI - STATUS of penicillin treatment of early syphilis. PMID- 21007547 TI - Present status of homologous serum jaundice. PMID- 21007549 TI - CIVILIAN survey of the Army's amputation program. PMID- 21007548 TI - CORNEAL edema; unusual toxic reaction to atabrine. PMID- 21007550 TI - EXTERNAL otitis in the tropics. PMID- 21007551 TI - LABORATORY aids in diagnosis of primary atypical pneumonia. PMID- 21007552 TI - MODIFIED mosquito light trap. PMID- 21007553 TI - PROBLEM of burns in military surgery. PMID- 21007554 TI - STUDY of psychosomatic dermatological syndromes. PMID- 21007555 TI - FELLOWSHIPS in medical research. PMID- 21007556 TI - FLY control with DDT. PMID- 21007557 TI - LABORATORY methods used for the recognition of influenza. PMID- 21007558 TI - DEATHS in American land forces during major wars. PMID- 21007559 TI - Antistreptococcal antibodies. PMID- 21007561 TI - GUIDES to historical writing. PMID- 21007560 TI - PROPOSED postwar Medical Department plan. PMID- 21007562 TI - The medical approach to the patient in the Army. PMID- 21007563 TI - Balanced suspension and fractures of the femur. PMID- 21007564 TI - Nutritional aspects of care of paralyzed patients. PMID- 21007565 TI - Simple method of removing vesical calculi in paraplegic patients. PMID- 21007566 TI - Jaw relationship records; vertical dimension and centric. PMID- 21007567 TI - Psychiatry in the Fifth Army area. PMID- 21007568 TI - Clinical experience with snake bites on Okinawa. PMID- 21007569 TI - Treatment of patient at sea. PMID- 21007570 TI - Relation of the Weil-Felix reaction to the clinical course of Tsutsugamushi disease. PMID- 21007571 TI - Processing Del-Mar-Va poultry for the Armed Forces. PMID- 21007572 TI - Bacterial flora in cantonment-type surgical ward. PMID- 21007573 TI - Radiation characteristics of the field x-ray unit used for superficial therapy. PMID- 21007574 TI - A clinical test of nerve regeneration. PMID- 21007575 TI - Stevens-Johnson's disease in edentulous mouth; report of case. PMID- 21007576 TI - The detection of methanol in blood-methanol mixtures; preliminary note. PMID- 21007577 TI - Methyl alcohol poisoning; report of cases. PMID- 21007579 TI - Brucellosis. PMID- 21007578 TI - Analysis of advanced reconditioning cases. PMID- 21007580 TI - NEW powder for fungus infections. PMID- 21007581 TI - Foot care for your crew. PMID- 21007582 TI - Marine art. PMID- 21007583 TI - Salt deficiency states in tropical climates. PMID- 21007584 TI - Biliary colic and chronic pancreatitis. PMID- 21007585 TI - Pseudo-leukaemic eosinophilia complicated by gangrenous appendicitis, as a possible manifestation of infectious mononucleosis, with observations on the mutual antagnism between lymphocytes and granulocytes. PMID- 21007586 TI - Traumatic lesions of the spinal cord. PMID- 21007587 TI - A summer tour in the Persian Gulf. PMID- 21007588 TI - Remarks on acclimatization. PMID- 21007589 TI - A psychiatric survey of naval personnel. PMID- 21007590 TI - Recent advances in malaria control. PMID- 21007591 TI - Apparent lack of response to quinine and mepacrine in cases of subtertian malaria. PMID- 21007592 TI - Traumatic aneurysm of the femoral artery. PMID- 21007593 TI - Prickley heat and tropical pemphigus. PMID- 21007594 TI - Methods of accelerating dark adaptation and improving night vision. PMID- 21007595 TI - Syndrome of oxygen poisoning in cats. PMID- 21007596 TI - Development of psychiatry in the Army in World War II. PMID- 21007597 TI - Psychiatric study of 100 battle veterans. PMID- 21007598 TI - Psychiatry aboard a hospital ship during the attack on Pearl Harbor. PMID- 21007599 TI - Psychiatric disorders in Puerto Rican troops. PMID- 21007600 TI - Psychosis following administration of quinacrine hydrochloride for malaria; neuropsychiatric study of a case. PMID- 21007601 TI - Delayed combat reactions in Air Force personnel. PMID- 21007602 TI - Measurement of skin resistance in peripheral nerve injuries. PMID- 21007604 TI - Anew hypothesis for the mechanism of activation of substrate molecules by enzymes. PMID- 21007603 TI - HAFFKINE INSTITUTE. PMID- 21007605 TI - On dicoumarin-synthetic anti-coagulant. PMID- 21007606 TI - A preliminary note on the antibacterial substance from Aspergillus flavus. PMID- 21007607 TI - Studies in the sulphur formation at Kona, Masulipatam. II. PMID- 21007608 TI - Role of water-soluble phosphoric acid as an aspect of sewage irrigation. PMID- 21007609 TI - Occurrence of gossypol. PMID- 21007610 TI - Seed transmission of melon mosaic virus. PMID- 21007611 TI - Osteometric determination of sex from the head and the lower end of the femur. PMID- 21007612 TI - On a new coccidium Wenyonella gallinae from the gut of the domestic fowl, Gallus gallus domesticus Linn. PMID- 21007613 TI - Determination of the purity of hydrocarbons by measurement of freezing points. PMID- 21007614 TI - Second dissociation constant of o-phthalic acid and related pH values of phthalate buffers from 0 degrees to 60 degrees C. PMID- 21007615 TI - Oxidation of galacturonic acid and of 5-keto-gluconic acid in alkaline solution. PMID- 21007616 TI - The mission of science. PMID- 21007617 TI - An electrical hypothesis of synaptic and neuromuscular transmission. PMID- 21007618 TI - Porphyrin fluorescence in the livers of pellagrins in relation to ultra-violet light. PMID- 21007619 TI - Acetylphosphatase in animal tissues. PMID- 21007620 TI - Use of growth-promoting substances in the prevention of apple drop following frost. PMID- 21007621 TI - Acoustic control in the flight of bats. PMID- 21007622 TI - Life-time of the neutral meson. PMID- 21007623 TI - Autoxidation of linoleic acid. PMID- 21007624 TI - Primary degradation products of mepacrine in human urines. PMID- 21007625 TI - Parathyroidectomy and lactation in the rat. PMID- 21007626 TI - Nature of the gram-positive complex in micro-organisms. PMID- 21007627 TI - Excavations at Hyrax Hill, Nakuru, Kenya Colony. PMID- 21007628 TI - Hospital diet. PMID- 21007629 TI - Science and reconstruction. PMID- 21007630 TI - The edibility of birds. PMID- 21007631 TI - Experimental imitation of tumour conditions. PMID- 21007632 TI - Adsorption isotherms from chromatographic measurements. PMID- 21007634 TI - Differentiation of nuclear substances. PMID- 21007633 TI - Efficacy of D.D.T. in soap. PMID- 21007635 TI - Cytological reactions induced by inorganic salt solutions. PMID- 21007637 TI - Mode of entry of contact insecticides. PMID- 21007636 TI - Carboxylase and carbonic acid. PMID- 21007638 TI - Ergot on Pennisetum Hohenackeri Hochst. PMID- 21007639 TI - Human chromosomes. PMID- 21007640 TI - A direct-reading photoelectric colorimeter. PMID- 21007641 TI - A simple refractoscope for liquids. PMID- 21007642 TI - A useful seal for dynamic vacuum systems. PMID- 21007643 TI - A refractometer. PMID- 21007644 TI - DOUBLE-BEAM cathode-ray tube. PMID- 21007645 TI - Who has the earth's uranium? PMID- 21007646 TI - CHEMISTRY of penicillin. PMID- 21007647 TI - Science and the Government. PMID- 21007648 TI - Further studies on the monkey anti-anemia factor. PMID- 21007649 TI - Demonstration of influenza virus, Type B, in a recent outbreak of upper respiratory infection. PMID- 21007650 TI - Transmission of the toxicity of DDT through the milk of white rats and goats. PMID- 21007651 TI - A fog or aerosol applicator for DDT. PMID- 21007652 TI - Science legislation. PMID- 21007653 TI - WARTIME research in malaria. PMID- 21007654 TI - Science legislation and the holiday recess. PMID- 21007655 TI - The lipotropic properties of inositol. PMID- 21007656 TI - TDE, 1,1-dichloro 2,2-bis (p-chlorophenyl) ethane, as an anopheline larvicide. PMID- 21007657 TI - Black fly incubator-aerator cabinet. PMID- 21007658 TI - Attachment of electroencephalographic electrodes. PMID- 21007659 TI - A new glass device for staining cover-glass preparations. PMID- 21007660 TI - Growth of trophoblast in the anterior chamber of the eye of the rabbit. PMID- 21007661 TI - Freezing behavior in rats. PMID- 21007662 TI - New opportunities and new responsibilities for the psychologist. PMID- 21007663 TI - Electrical correlates of peripheral nerve injury; a preliminary note. PMID- 21007664 TI - Spinal conditioning in dogs. PMID- 21007665 TI - A gastric mucigogue action of the alkyl sulfates. PMID- 21007666 TI - Degradation of streptomycin and the structure of streptidine and streptamine. PMID- 21007667 TI - A photographic method for recording ureteral kinetics in situ. PMID- 21007668 TI - The estimation of streptomycin in body fluids. PMID- 21007669 TI - Continuous anesthesia for insects. PMID- 21007670 TI - Ch'ang Shan, a Chinese antimalarial drug. PMID- 21007671 TI - State sterilization programs for the prophylactic control of mental disease and mental deficiency. PMID- 21007672 TI - Electroencephalographic study of criminals. PMID- 21007673 TI - The correlation of pre-electroshock electroencephalogram and therapeutic result in schizophrenia. PMID- 21007674 TI - An electroencephalographic study of cases with syncope and related disorders. PMID- 21007675 TI - The electroencephalogram in some military and selective service convulsive and non-convulsive problems. PMID- 21007676 TI - Some reactions seen after electric shock treatment. PMID- 21007677 TI - The prophylaxis of cardiac complications in electroshock therapy. PMID- 21007678 TI - Organic and hysterical anesthesia; a method of differential diagnosis with the aid of the galvanic skin response. PMID- 21007679 TI - Ageing and detoxication; studies in hippuric acid synthesis during psychoses of the involutional and old age group. PMID- 21007680 TI - Psychoanalysis and the unconscious. PMID- 21007682 TI - Attitudes of soldiers returning from overseas service. PMID- 21007681 TI - The personality of the successful soldier. PMID- 21007683 TI - A brief history of family care of mental patients in America. PMID- 21007684 TI - A total psychotherapeutic push method as practiced in the Fifth Service Command Rehabilitation Center, Fort Knox, Kentucky. PMID- 21007686 TI - Conquering war strain in children. PMID- 21007685 TI - Emotional adjustment of newly blinded soldiers. PMID- 21007687 TI - The autobiographical study as an aid to psychotherapy. PMID- 21007688 TI - The central nervous system in morphinism. PMID- 21007689 TI - Some relationships between excitement, depression and anxiety. PMID- 21007690 TI - Self-induced psychosis with hyperthyroidism complicating manic depressive psychosis. PMID- 21007691 TI - The autokinetic test; its value in psychiatric diagnosis and prognosis; preliminary report. PMID- 21007692 TI - A note on apomorphine as a sedative. PMID- 21007693 TI - Diagnosis and classification; a distinction. PMID- 21007694 TI - Discussion of Dr. Bassoe's article, Spain as the cradle of psychiatry. PMID- 21007695 TI - The psychiatry-anthropology relationship. PMID- 21007696 TI - A state program of eleemosynary care. PMID- 21007697 TI - Analysis of neuropsychiatric rejectees from the state of Tennessee. PMID- 21007698 TI - Neurotic behavior patterns arising out of the combat situation. PMID- 21007699 TI - Tuberculous meningitis. PMID- 21007700 TI - The fear-allaying effect of pentothal sodium in electro-shock therapy. PMID- 21007701 TI - Ontogeny of bisexual differentiation in man. PMID- 21007702 TI - Unconscious processes in artistic creation. PMID- 21007703 TI - About the name and some pathologic functions of the unconscious. PMID- 21007705 TI - Facts and figures on psychotherapy. PMID- 21007704 TI - Oliver Cromwell and the Puritan Revolution. PMID- 21007706 TI - Roentgenological studies of the gastrointestinal tract in psychosomatic conditions. PMID- 21007707 TI - A psychosomatic study of myself. PMID- 21007708 TI - The Woodworth Personal Data Sheet as applied to delinquents. PMID- 21007709 TI - Motives of insomnia. PMID- 21007710 TI - Pituitary adenoma associated with chronic duodenal ulcer. PMID- 21007711 TI - Reflex differences in hypoglycemic schizophrenics with a few remarks on the possible role of the right hemisphere in the production of some mental symptoms. PMID- 21007712 TI - The psychiatric evaluation of naval personnel returning from combat and overseas duty. PMID- 21007713 TI - The significance of the depth of the physiologic cup of the optic disc for mental ability. PMID- 21007714 TI - The diagnosis and classification of neurotic states; a reinterpretation of Eysenck's factors. PMID- 21007715 TI - The combat induced anxiety state as seen after return to duty. PMID- 21007716 TI - Aminoacetic acid (glycine) in the treatment of depression. PMID- 21007717 TI - Electroencephalographic findings in psychopathic personalities. PMID- 21007718 TI - The natural history of sciatic neuritis. PMID- 21007719 TI - Acute alterable states in multiple sclerosis. PMID- 21007720 TI - Some reactions seens after electric shock treatment. PMID- 21007721 TI - Transventricular wounds of the brain. PMID- 21007722 TI - Extensive brain wounds; analysis of 159 cases occurring in a series of 342 penetrating war wounds of the brain. PMID- 21007723 TI - Spasm of the internal carotid artery. PMID- 21007724 TI - Neurogenic ossifying fibromyopathies; a preliminary report. PMID- 21007725 TI - Serous meningitis. PMID- 21007726 TI - Prevention of nerve regeneration and neuroma formation by caps of synthetic resin. PMID- 21007727 TI - Early nerve and bone repair in war wounds. PMID- 21007728 TI - The antigenicity of bovine thrombin; clinical evaluation. PMID- 21007729 TI - Extradural pneumatocele following tantalum cranioplasty. PMID- 21007730 TI - Clovis Vincent. PMID- 21007731 TI - Case reports and technical notes; anterior sacral meningocele. PMID- 21007732 TI - Fulminating gas gangrene of the brain; report of a case in a civilian. PMID- 21007733 TI - Cysticercosis; a case report. PMID- 21007735 TI - Peripheral nerve lesion charts. PMID- 21007734 TI - A new position for frontal craniotomy. PMID- 21007736 TI - [Not Available]. PMID- 21007737 TI - [Not Available]. PMID- 21007738 TI - [Not Available]. PMID- 21007739 TI - [Not Available]. PMID- 21007740 TI - Anatomical study of traumatic disease of the spinal cord. PMID- 21007741 TI - Lesions of the spine and spinal cord and the methods of their treatment (the early and late periods). PMID- 21007742 TI - Sequelae of early surgical interference in gunshot wounds of the spine and spinal cord. PMID- 21007743 TI - Gunshot lesions of the spinal column and spinal cord. PMID- 21007744 TI - A study of the significance of disturbances of the function of the vegetative centres of the spinal cord in pathogenesis of complications of wounds of the spine and spinal cord. PMID- 21007745 TI - Gunshot injuries of the cauda equina. PMID- 21007746 TI - Suprapubic fistula in spinal traumae. PMID- 21007747 TI - Work of a spinal department of a front evacuo-hospital. PMID- 21007748 TI - Chronaxia of the radices spinales in gunshot traumae of the spine and spinal cord. PMID- 21007749 TI - Employment of rhythmical irritations as a new method of study in the diagnostics of traumae of the nervous system. PMID- 21007750 TI - The sudden change of the lability of the neuro-muscular synapsis in operations on the spinal cord. PMID- 21007751 TI - The problem of the paralyzed bladder. PMID- 21007752 TI - The care, maintenance and conservation of hospital equipment. PMID- 21007753 TI - Using the psychological approach. PMID- 21007754 TI - The industrial nurse and her approach to her job. PMID- 21007755 TI - Personal adjustments in industrial nursing. PMID- 21007756 TI - The plant safety program; the nurse's influence. PMID- 21007757 TI - The anaemias. PMID- 21007758 TI - Septic thrombosis of the cavernous sinus followed by encephalitis. PMID- 21007759 TI - Ideal house for the district nurse. PMID- 21007760 TI - The management of abortion; description and causes. PMID- 21007761 TI - Modern methods of controlling infection during the puerperium. PMID- 21007762 TI - The modern treatment of fractures. PMID- 21007763 TI - In a Japanese internment camp. PMID- 21007764 TI - The teaching of normal psychology to the student nurse. PMID- 21007765 TI - Modern means of controlling infection in the neo-natal and early infancy periods. PMID- 21007767 TI - Epilepsy and the public health nurse. PMID- 21007766 TI - Drugs for the cure of tuberculosis. PMID- 21007768 TI - An orthopedic service for the community. PMID- 21007769 TI - SUGGESTED school health policies; services for health protection and improvement. PMID- 21007770 TI - Persistence and hyperplasia of the primary vitreous (tunica vasulosa lentis or retrolental fibroplasia). PMID- 21007771 TI - Graduate training in ophthalmology. PMID- 21007772 TI - Report from the Wilmer Institute on the results obtained in the treatment of myopia by visual training. PMID- 21007773 TI - Eye conditions among children of premature, full-term, and hypermature birth. PMID- 21007774 TI - Vision in industry. PMID- 21007775 TI - A visual test for infants. PMID- 21007776 TI - Repeatability of keratometric readings. PMID- 21007777 TI - A case of multiple tuberculous nodules of the episclera. PMID- 21007778 TI - A tendon-transplantation technique for externalrectus paralysis. PMID- 21007779 TI - The Herbert iris-incarceration method of operation for glaucoma. PMID- 21007780 TI - Retinis circinata of unknown origin in a child. PMID- 21007781 TI - Syphilitic optic atrophy and tryparsamide amblyopia. PMID- 21007782 TI - Involvement of the ocular system in demyelinating diseases. PMID- 21007783 TI - Sympathetic ophthalmitis following iridencleisis. PMID- 21007784 TI - Cyclodiathermy. PMID- 21007786 TI - Keratoconjunctivitis sicca. PMID- 21007785 TI - Keratitis sicca. PMID- 21007787 TI - Chronic blepharoconjunctivitis due to lid warts. PMID- 21007788 TI - The need for more basic courses in ophthalmology. PMID- 21007789 TI - Refractive significance of Ortho-Rater tests. PMID- 21007790 TI - Visual education. PMID- 21007792 TI - [Not Available]. PMID- 21007791 TI - Strabismus. PMID- 21007793 TI - [Not Available]. PMID- 21007794 TI - [Not Available]. PMID- 21007795 TI - [Not Available]. PMID- 21007796 TI - [Not Available]. PMID- 21007797 TI - [Not Available]. PMID- 21007798 TI - [Not Available]. PMID- 21007799 TI - [Not Available]. PMID- 21007800 TI - [Not Available]. PMID- 21007801 TI - [Not Available]. PMID- 21007803 TI - [Not Available]. PMID- 21007802 TI - [Not Available]. PMID- 21007804 TI - [Not Available]. PMID- 21007805 TI - [Not Available]. PMID- 21007806 TI - [Not Available]. PMID- 21007807 TI - [Not Available]. PMID- 21007808 TI - A versatile infra-red spectrograph. PMID- 21007809 TI - Alternating-current bolometer for infra-red spectroscopy. PMID- 21007810 TI - An improved screening test for red-green color deficiency composed of available pseudo-isochromatic plates. PMID- 21007811 TI - Specification of railroad signal colors and glasses. PMID- 21007812 TI - Transmittance and reflectance of germicidal energy. PMID- 21007813 TI - Spectrophotometrical determinations of nucleic acids and nucleases in cerebrospinal fluids after cerebral concussion. PMID- 21007814 TI - Pharmacological responses of some previously x-rayed animals and plants. PMID- 21007815 TI - Sunglasses and sunglass lenses. PMID- 21007817 TI - Vision and the selection of personnel in industry. PMID- 21007816 TI - The referring of ocular pathology. PMID- 21007818 TI - Glaucoma and the prevention of blindness. PMID- 21007819 TI - Medical social service with glaucoma patients. PMID- 21007820 TI - Glaucoma clinic procedures. PMID- 21007821 TI - Some impressions of oto-rhinolaryngology in Germany to-day. PMID- 21007822 TI - Fenestration of the labyrinth. PMID- 21007823 TI - Case of left temporal lobe abscess, extradural abscess and lateral sinus thrombosis, following exacerbation of chronic suppurative otitis media, drainage, recovery. PMID- 21007825 TI - An improved method for classifying audiograms. PMID- 21007824 TI - Nutrition in ophthalmology and otolaryngology. PMID- 21007826 TI - Blast injuries of the ear. PMID- 21007827 TI - [Not Available]. PMID- 21007828 TI - [Not Available]. PMID- 21007829 TI - [Not Available]. PMID- 21007830 TI - [Not Available]. PMID- 21007831 TI - [Not Available]. PMID- 21007832 TI - [Not Available]. PMID- 21007833 TI - [Not Available]. PMID- 21007834 TI - [Not Available]. PMID- 21007835 TI - [Not Available]. PMID- 21007836 TI - An outline of the history of pediatrics in Sweden. PMID- 21007837 TI - Social welfare of Swedish children, past and present. PMID- 21007838 TI - The pediatric clinics of the universities and medical colleges as main centres of medical and medico-social pediatric care, research and instruction. PMID- 21007840 TI - Roentgenologic determination of heart volume in infants. PMID- 21007839 TI - Primary tumours of the optic nerve and their relation to Recklinghausen's disease. PMID- 21007841 TI - On acute nicotine poisoning. PMID- 21007842 TI - Poliomyelitis and its prognosis in Sweden; condition and capacity for work after nine years' observation. PMID- 21007843 TI - [Not Available]. PMID- 21007844 TI - The duration of physiological icterus neonatorum. PMID- 21007845 TI - Sulfanilamide drugs and acute nephritis. PMID- 21007846 TI - The treatment of morbus haemolyticus neonatorum (familial erythroblastosis foetalis); guiding lines for experiments towards an improvement. PMID- 21007847 TI - Experimentally produced gallop rhythm; a preliminary report. PMID- 21007848 TI - Megacolon in the newborn; a clinical and rontgenological study with special regard to the pathogenesis; a preliminary report. PMID- 21007849 TI - Treatment of pyloric stenosis in infants with methylscopolamine nitrate. PMID- 21007850 TI - The reaction of first-born children in infectious diseases. PMID- 21007851 TI - Acute rheumatic infection in children; clinical studies with special reference to the initial phase and the valuation of the cardiologic and hematologic signs. PMID- 21007852 TI - [Not Available]. PMID- 21007853 TI - Electro-encephalographic examinations of imbeciles; regarding the alpha frequency in spastics and mongoloid idiots. PMID- 21007854 TI - The present organization of school hygiene in Sweden. PMID- 21007856 TI - Instruction in social pediatrics. PMID- 21007855 TI - What is the cause of Harrison's groove in rickety infants? PMID- 21007857 TI - The syndroma hypoglycemia-hydrops-erythroblastemia in new-born. PMID- 21007859 TI - Pernicious anaemia in children. PMID- 21007858 TI - Massive dose prophylaxis with vitamin D for prematurely born infants. PMID- 21007860 TI - Bacteriological examination of throat tests from children. PMID- 21007861 TI - Three years' prophylaxis against rickets in prematures, with D2 massive dose. PMID- 21007862 TI - Moniliosis of the respiratory tract; bronchomoniliosis. PMID- 21007863 TI - Chemo-prophylaxis against nosocomial infections. PMID- 21007864 TI - Treatment of children's diabetes; ten years' experience without dietetic restrictions. PMID- 21007865 TI - [Not Available]. PMID- 21007866 TI - Some notes on the development of memory during the first years of life. PMID- 21007867 TI - [Not Available]. PMID- 21007868 TI - Occurrence and significance of early periosteal proliferation in the diaphyses of premature infants. PMID- 21007869 TI - Patent ductus arteriosus; diagnosis and indications for operation. PMID- 21007870 TI - On the relationship between prothrombin time and haematocrit value. PMID- 21007871 TI - Inflammatory processes in the central nervous system as a complication of scarlet fever. PMID- 21007872 TI - On casein from human and cow's milk and their behaviour on hydrolysis with different proteolytic enzymes; preliminary report. PMID- 21007873 TI - The Stockholm centre for distribution of mothers' milk. PMID- 21007875 TI - [Not Available]. PMID- 21007874 TI - The occurrence of erythema nodosum in children with primary tuberculosis, treated with sulfatiazol. PMID- 21007876 TI - [Not Available]. PMID- 21007877 TI - The relation between infantile tetany and rickets. PMID- 21007878 TI - Exanthema neonatorum from the allergic viewpoint, especially concerning the influence of orange and vitamin C supply to the mother. PMID- 21007879 TI - Variations in the fat content of collected human milk. PMID- 21007880 TI - Studies on the absorption of iron; absorption of iron from the stomach. PMID- 21007881 TI - Breast-milk consumption of healthy full-term infants. PMID- 21007882 TI - [Not Available]. PMID- 21007883 TI - On shock in premature children; preliminary report. PMID- 21007884 TI - [Not Available]. PMID- 21007885 TI - [Not Available]. PMID- 21007886 TI - [Not Available]. PMID- 21007887 TI - [Not Available]. PMID- 21007888 TI - [Not Available]. PMID- 21007889 TI - [Not Available]. PMID- 21007890 TI - [Not Available]. PMID- 21007891 TI - [Not Available]. PMID- 21007892 TI - [Not Available]. PMID- 21007894 TI - Little's disease; with report of a family. PMID- 21007893 TI - [Not Available]. PMID- 21007895 TI - A typical hereditary ataxia. PMID- 21007896 TI - Penicillin treatment of pneumococcus meningitis in infants. PMID- 21007897 TI - The prevention of rheumatic recurrences in children by the use of sulfathiazole and sulfadiazine. PMID- 21007898 TI - Rickets: a study of calcium and phosphorus metabolism and of clinical findings as influenced by certain feedings. PMID- 21007899 TI - Proctological problems of the pediatrician. PMID- 21007900 TI - The heterophile antibody reaction in infants and children. PMID- 21007901 TI - Sedatives and stimulants in pediatric practice. PMID- 21007902 TI - Chorea in the Negro race. PMID- 21007903 TI - Tracheotomy in bulbar poliomyelitis. PMID- 21007904 TI - Cardiospasm in the newborn. PMID- 21007905 TI - Meningitis caused by type F Hemophilus influenzae; report of a case with recovery. PMID- 21007906 TI - The treatment with antiserum of acute laryngitis caused by Hemophilus influenzae. PMID- 21007907 TI - Meningococcic meningitis; a report of multiple cases occurring in the same family. PMID- 21007908 TI - Cystic tuberculosis of the bone in a case of miliary tuberculosis. PMID- 21007909 TI - Arachnodactyly; unusual complication following skull injury. PMID- 21007910 TI - The treatment of acute suppurative parotitis in infants. PMID- 21007911 TI - Hereditary skin defects in the newborn infant. PMID- 21007912 TI - Generalized vaccinia and probable induced thiamine deficiency in a congenitally hypothyroid child. PMID- 21007913 TI - The Greenberg modification of the Flagg laryngoscope; its use in asphyxia neonatorum. PMID- 21007914 TI - Communication on the Pepper Bill S.1318; a medical care credo; medical education. PMID- 21007915 TI - [Not Available]. PMID- 21007916 TI - [Not Available]. PMID- 21007917 TI - The scope of pharmacy; an exhibit. PMID- 21007918 TI - One: four vs two: three division of prepharmaceutic and pharmaceutic study. PMID- 21007919 TI - INFLUENZA virus vaccine, A and B. PMID- 21007920 TI - Aminoacid mixtures. PMID- 21007921 TI - HIGHLIGHTS of 1945 achievements in pharmacy and related fields. PMID- 21007922 TI - Pharmacy of penicillin used by inhalation. PMID- 21007923 TI - Continuous intravenous chemotherapy of Plasmodium lophurae infection in ducks. PMID- 21007924 TI - A short-term chronic toxicity test employing mice. PMID- 21007925 TI - The central stimulant action of some basopressor amines. PMID- 21007926 TI - Observations on the nature of the antagonism of histamine by beta dimethylaminoethyl benzhydryl ether (benadryl). PMID- 21007927 TI - Antithyroid studies; the goitrogenic activity of certain chemotherapeutically active sulfones and related compounds. PMID- 21007928 TI - Studies on the mechanism of action of sympathomimetic amines. PMID- 21007929 TI - Studies on the mechanism of action of sympathomimetic amines; the effect of sympathomimetic amines on the succinoxidase system as influenced by the presence of alpha-tocopherol phosphate. PMID- 21007930 TI - Studies on shock induced by hemorrhage; isolation of a lactic dehydrogenase inhibitor from liver. PMID- 21007931 TI - Studies on shock induced by hemorrhage; the effects of injection into dogs of amino acid oxidase inhibitor. PMID- 21007932 TI - The effect of digitalis upon coagulation time of the blood. PMID- 21007933 TI - Studies on antimalarial drugs; the metabolism of quinine and quinidine in birds and mammals. PMID- 21007934 TI - The effect of different intravenous injection rates upon the AD50, LD50 and anesthetic duration of pentothal in mice, and strength-duration curves of depression. PMID- 21007935 TI - The effect of ether, divinyl ether and cyclopropane anesthesia upon the heart rate and rhythm and blood pressure during normal respiratory activity and during artificial respiration after respiratory arrest. PMID- 21007936 TI - Studies on cyclopropane; the effect of premedication with demerol upon the heart rate, rhythm and blood pressure in dogs under cyclopropane anesthesia. PMID- 21007937 TI - The degradation of quinine in the duck, chicken and dog. PMID- 21007938 TI - The chronic toxicity of quinacrine (atabrine). PMID- 21007939 TI - The antidiuretic action of barbiturates (phenobarbital, amytal, pentobarbital) and the mechanism involved in this action. PMID- 21007940 TI - The absorption of thiourea from ointments applied to wounds. PMID- 21007941 TI - Antibiotic substances active against M. tuberculosis. PMID- 21007942 TI - Sulfonamides for bacillary dysentery; the antibacterial activity of sulfacarboxythiazoles and sulfathiadiazole. PMID- 21007943 TI - The inhibitory effect of atabrine and some acridine derivatives upon acid-fast bacilli in vitro. PMID- 21007944 TI - The spirocheticidal and trypanocidal action of acid-substituted phenyl arsenoxides as a function of pH and dissociation constants. PMID- 21007945 TI - The sympathomimetic vasodilating action of the aliphatic amines. PMID- 21007947 TI - DYSMENORRHEA. PMID- 21007946 TI - HYPERTENSION; its causes and treatment. PMID- 21007948 TI - Studies on malarial parasites; the staining of two primate parasites by the Feulgen technique. PMID- 21007949 TI - Effects of ultraviolet irradiation on corneal epithelium; mitosis, nuclear fragmentation, post-traumatic cell movements, loss of tissue cohesion. PMID- 21007950 TI - Intensity effects of ultraviolet radiation of wavelength 2537 A on mitosis in the grasshopper neuroblast. PMID- 21007951 TI - Localization of adenylpyrophosphatase in cytoplasmic granules. PMID- 21007952 TI - Note on the red luminescence and the red pigment of the railroad worm. PMID- 21007953 TI - Military job evaluation: Army Air Forces. PMID- 21007954 TI - A statistical study of visual functions and industrial safety. PMID- 21007955 TI - Effect of visual adaptation upon intensity of illumination preferred for reading with direct lighting. PMID- 21007956 TI - Mechanical aptitudes of university women. PMID- 21007957 TI - Aptitude and interest patterns of art majors in a liberal arts college. PMID- 21007958 TI - An empirical evaluation of study habits for college courses in French and Spanish. PMID- 21007959 TI - Personality traits associated with abilities; with verbal and mathematical abilities. PMID- 21007960 TI - Rate of visual perception as a factor in rate of reading. PMID- 21007961 TI - A comment on the correction of reliability coefficients for restriction of range. PMID- 21007962 TI - A study of the production of pleasant and unpleasant items as related to adolescent development. PMID- 21007963 TI - Personality adjustments of children belonging to two minority groups. PMID- 21007964 TI - Relation of marks in college courses to the interestingness, value, and difficulty of the courses. PMID- 21007965 TI - An exploratory investigation of language by means of oscillographic and reaction time techniques. PMID- 21007966 TI - Fluctuation of sensation of liminal visual stimuli. PMID- 21007967 TI - Visual acuity and distance of observation. PMID- 21007968 TI - Primary and secondary suggestibility; an experimental and statistical study. PMID- 21007969 TI - A repetition of the Blodgett experiment of latent learning. PMID- 21007970 TI - The effects of attitudes on descriptions of pictures. PMID- 21007971 TI - A psychological study of Stalin. PMID- 21007972 TI - Personal values and religious backgrounds. PMID- 21007973 TI - The values of Negro women college students. PMID- 21007974 TI - Studies in beauty; some determiners of the perception of beauty in women. PMID- 21007975 TI - The use of interviewer rapport as a method of detecting differences between public and private opinion. PMID- 21007976 TI - Cultural conflict and the feminine role; an experimental study. PMID- 21007977 TI - A mutual validation of personality traits. PMID- 21007978 TI - The essence of democracy. PMID- 21007979 TI - Youth and progress. PMID- 21007980 TI - Student attitudes toward religious practices. PMID- 21007981 TI - CHARLES SPEARMAN, 1863-1945. PMID- 21007982 TI - The prediction of choice. PMID- 21007983 TI - A basis for analyzing test-retest reliability. PMID- 21007984 TI - A simple orthogonal multiple factor approximation procedure. PMID- 21007985 TI - PROVINCIALISATION of public health services. PMID- 21007986 TI - Trends in under- and post-graduate teaching of public health and preventive medicine. PMID- 21007987 TI - DEATH and disease in Bengal famine. PMID- 21007988 TI - The problem of malaria. PMID- 21007989 TI - Some landmarks and lacunae in malariology in Bengal. PMID- 21007990 TI - Food for the people. PMID- 21007991 TI - Public health administration in Bengal. PMID- 21007992 TI - Social hygiene work in Calcutta. PMID- 21007993 TI - School health service in Bengal. PMID- 21007994 TI - Public health administration of Bengal. PMID- 21007995 TI - Planning for maternal and child health. PMID- 21007996 TI - Anti-malaria drainage for Bengal. PMID- 21007997 TI - The tuberculosis problem in Bengal. PMID- 21007998 TI - The fallacies as I see them. PMID- 21007999 TI - [Not Available]. PMID- 21008000 TI - [Not Available]. PMID- 21008001 TI - [Not Available]. PMID- 21008002 TI - [Not Available]. PMID- 21008003 TI - [Not Available]. PMID- 21008004 TI - [Not Available]. PMID- 21008005 TI - [Not Available]. PMID- 21008006 TI - [Not Available]. PMID- 21008008 TI - [Not Available]. PMID- 21008007 TI - HEALTH precautions for visitors to the tropics. PMID- 21008009 TI - [Not Available]. PMID- 21008010 TI - [Not Available]. PMID- 21008011 TI - The courts cooperate in controlling venereal disease. PMID- 21008012 TI - Typhoid fever from clams. PMID- 21008013 TI - An examination of the decline in non-pulmonary tuberculosis, and particularly abdominal tuberculosis, in the age group 15 years and upwards in London and rural districts of England and Wales and the South-Eastern counties between 1911 and 1938. PMID- 21008014 TI - Hostels for the aged. PMID- 21008015 TI - The death-rate of midwives. PMID- 21008016 TI - FERTILITY and educational level of parents. PMID- 21008017 TI - Fifty years of roentgen rays. PMID- 21008018 TI - Pictures of organic molecules from x-ray diffraction data. PMID- 21008019 TI - A million-volt chest radiograph. PMID- 21008020 TI - Radiography of the pisiform bone. PMID- 21008021 TI - An easily made serialograph. PMID- 21008022 TI - Infrared photography of patients. PMID- 21008023 TI - Extra-uterine pregnancy; a fetal skeleton. PMID- 21008024 TI - Osteitis deformans with involvement of humerus. PMID- 21008025 TI - The teaching of radiology. PMID- 21008026 TI - The clinical significance of deformity of the cecum in amebiasis. PMID- 21008027 TI - Roentgen findings in amebic disease of the liver. PMID- 21008028 TI - An evaluation of automatic exposure control equipment in photofluorography. PMID- 21008029 TI - An unusual case of Ewing's sarcoma. PMID- 21008030 TI - Roentgenologic visualization of the fractured temporal styloid process. PMID- 21008031 TI - Lipiodol intravasation during uterosalpingography with pulmonary complications. PMID- 21008033 TI - The origin of cancer in man. PMID- 21008032 TI - Bone rarefaction after skull injuries. PMID- 21008034 TI - DANGERS INHERENT in scattered cathode rays. PMID- 21008035 TI - [Not Available]. PMID- 21008036 TI - [Not Available]. PMID- 21008037 TI - [Not Available]. PMID- 21008038 TI - [Not Available]. PMID- 21008039 TI - [Not Available]. PMID- 21008040 TI - [Not Available]. PMID- 21008041 TI - [Not Available]. PMID- 21008042 TI - [Not Available]. PMID- 21008043 TI - [Not Available]. PMID- 21008044 TI - [Not Available]. PMID- 21008045 TI - [Not Available]. PMID- 21008046 TI - A comparison of amphetamine sulfate with other stimulants of the central nervous system in morphine respiratory depression. PMID- 21008047 TI - Hypobaric pontocaine; a new technic in spinal anaesthesia. PMID- 21008048 TI - The utility of apomorphine in clinical anesthesia. PMID- 21008049 TI - Anesthesia in a maxillo-facial surgical unit with the British Liberation Army. PMID- 21008050 TI - Ether-air anesthesia; a technic. PMID- 21008051 TI - Bilateral paralysis of the abducens and hypoglossal nerves following spinal anesthesia; case report. PMID- 21008053 TI - Regional nerve block anesthesia. PMID- 21008052 TI - Acetaldehyde, a volatile anesthetic and sympathetic stimulant. PMID- 21008054 TI - Elective early intubation. PMID- 21008055 TI - Curare in adult tonsillectomy. PMID- 21008056 TI - An endotracheal tube for babies. PMID- 21008057 TI - Lesions of the spinal epidural space producing cord compression. PMID- 21008058 TI - Resection of the lung in the treatment of pulmonary tuberculosis. PMID- 21008059 TI - Studies on muscle atrophy; a method of recording power in situ and observations on effect of position of immobilization on atrophy of disuse and denervation. PMID- 21008060 TI - Reestablishment of pancreatic secretion into the intestine after division of the pancreas; an experimental study. PMID- 21008061 TI - Intussusception of the vermiform appendix; report of a case. PMID- 21008062 TI - Progress in orthopedic surgery for 1944; a review prepared by an editorial board of the American Academy of Orthopaedic Surgeons; diseases of growing and of adult bone. PMID- 21008063 TI - Congenital deformities. PMID- 21008064 TI - Tumors of bone and of synovial membrane. PMID- 21008065 TI - Conditions involving the hip joint. PMID- 21008066 TI - Conditions involving the foot and ankle. PMID- 21008068 TI - The use of cancellous chips in bone-grafting. PMID- 21008067 TI - Iliac-bone transplantation. PMID- 21008069 TI - A method of treatment of chronic infective osteitis. PMID- 21008070 TI - Pyogenic osteomyelitis of the spine. PMID- 21008071 TI - Osteochondromata of the pelvic bones. PMID- 21008072 TI - Late rupture of extensor policis longus tendon following Colles's fracture. PMID- 21008073 TI - Orthoroentgenography as a method of measuring the bones of the lower extremities. PMID- 21008074 TI - Ligaments of the knee joint; the relationship of the ligament of Humphry to the ligament of Wrisberg. PMID- 21008075 TI - Treatment of fracture-dislocation of the interphalangeal joints of the hand. PMID- 21008076 TI - The position of the external hip joint in the above-the-knee prosthesis with pelvic suspension. PMID- 21008077 TI - Mutational dysostosis (cleidocranial dysostosis). PMID- 21008078 TI - Arthrodesis of the hip produced by internal fixation. PMID- 21008079 TI - Vertical traction in the early management of certain compound fractures of the femur. PMID- 21008080 TI - Resection of the clavicle in vascular surgery. PMID- 21008081 TI - Transverse sacral folds. PMID- 21008082 TI - Spastic flat-foot. PMID- 21008083 TI - Bacteriological examination of the gastric contents in the diagnosis and management of tuberculosis of the bones and joints. PMID- 21008084 TI - Fracture of the medial epicondyle with displacement into the elbow-joint. PMID- 21008085 TI - Contracture of the scalenus anterior, causing aneurysmal varix of right internal juglar vein, a case report. PMID- 21008086 TI - Survival of the head of the radius in a child after removal and replacement. PMID- 21008087 TI - Severe pelvic fractures treated by fixed skeletal traction; report of a case. PMID- 21008088 TI - Trichinosis as a cause of meralgia paraesthetica. PMID- 21008089 TI - Localized coccidioidomycosis of bone. PMID- 21008090 TI - Bilateral simultaneous dislocation of the shoulders. PMID- 21008091 TI - An appliance for the conservative treatment of acromioclavicular dislocation. PMID- 21008092 TI - Modification of Calot plaster jacket for immobilization of the cervical spine. PMID- 21008093 TI - A universal splint for deformities of the hand. PMID- 21008094 TI - An improved bone clamp and a plate for internal fixation of fractures. PMID- 21008096 TI - A night splint for the correction of genu valgum. PMID- 21008095 TI - A simple traction device for the reduction of fractures of the forearm. PMID- 21008097 TI - Glass cloth as a wound dressing. PMID- 21008098 TI - Localized bone cyst of the os calcis. PMID- 21008099 TI - A simple retractor for spinal surgery. PMID- 21008100 TI - Congenital dislocation of the hip. PMID- 21008101 TI - Traumatic wet lung; observations on certain physiologic fundamentals of thoracic trauma. PMID- 21008102 TI - The use and control of thoracic surgical teams of an auxiliary surgical group. PMID- 21008103 TI - Full-thickness flap closure of large thoracotomy due to chemical destruction of chest wall. PMID- 21008104 TI - Penicillin in pulmonary resection; preliminary report. PMID- 21008105 TI - Cylindroma of the bronchus; report of six cases. PMID- 21008106 TI - Spontaneous pneumothoraces occurring in patients undergoing peroral endoscopy. PMID- 21008107 TI - Experimental hemothorax. PMID- 21008108 TI - Nerve block in the treatment of thoracic injuries. PMID- 21008109 TI - Recovery from hemolytic Staphylococcus aureus bactermia attributed to penicillin therapy; case report. PMID- 21008110 TI - Aneurysm of the subclavian artery in an infant. PMID- 21008112 TI - PREPARING sterile materials. PMID- 21008111 TI - Ligature technic in tonsillectomies. PMID- 21008113 TI - Chronic sclerosing osteitis. PMID- 21008114 TI - The fibular bone graft in ununited fractures of the neck of the femur. PMID- 21008115 TI - Mortality after operation. PMID- 21008116 TI - Gastric adenomas; a pathologic study. PMID- 21008117 TI - Evaluation of posture based on structural and functional measurements. PMID- 21008118 TI - Ultraviolet radiation in the treatment of indolent, soft-tissue ulcerations. PMID- 21008119 TI - New and improved remedial exercise equipment, devised and improvised at Oliver General Hospital, Augusta, Ga. PMID- 21008120 TI - Psychological adjustments in activity therapy. PMID- 21008122 TI - MANAGEMENT of peripheral nerve injuries. PMID- 21008121 TI - Early treatment of combined bone and nerve lesions. PMID- 21008123 TI - ELASTIC splint for foot drop. PMID- 21008124 TI - [Not Available]. PMID- 21008125 TI - [Not Available]. PMID- 21008126 TI - [Not Available]. PMID- 21008127 TI - [Not Available]. PMID- 21008128 TI - [Not Available]. PMID- 21008129 TI - [Not Available]. PMID- 21008130 TI - [Not Available]. PMID- 21008131 TI - [Not Available]. PMID- 21008132 TI - [Not Available]. PMID- 21008133 TI - [Not Available]. PMID- 21008134 TI - [Not Available]. PMID- 21008135 TI - Silicosis; a clinical study. PMID- 21008136 TI - Poncet's disease; clinical observations on inflammatory and degenerative joint reactions in tuberculosis. PMID- 21008137 TI - Treatment of pulmonary tuberculosis with diasone. PMID- 21008138 TI - Strict bed rest in pulmonary tuberculosis; an appraisal. PMID- 21008139 TI - Tuberculosis in a tropical Naval hospital. PMID- 21008140 TI - End results of artificial pneumothorax. PMID- 21008141 TI - A suction cabinet for use in cavity aspiration (Monaldi). PMID- 21008142 TI - Anatomical studies on human tuberculosis; disseminated calcified small nodular hematogenous pulmonary tubercles, incidentally discovered. PMID- 21008143 TI - A comparison of the tuberculin patch test and the collodion-tuberculin test. PMID- 21008144 TI - A modified tuberculin patch test. PMID- 21008145 TI - Clorox digestion; a comparison of clorox digestion and three other methods for finding acid-fast organisms in sputum. PMID- 21008146 TI - Medicine as practiced during the 1840's. PMID- 21008147 TI - Tuberculosis control in hospitals. PMID- 21008148 TI - Public health work in Korea. PMID- 21008150 TI - TUBERCULOSIS and parenthood. PMID- 21008149 TI - Respiratory diseases. PMID- 21008151 TI - [Phenomenon of hypoventilation of the pulmonary tissue in tuberculosis of the bronchial glands]. PMID- 21008152 TI - [Ascorbic acid in experimental tuberculosis of guinea pigs]. PMID- 21008153 TI - [On drip transfusion of blood in tuberculosis of the lungs]. PMID- 21008154 TI - [Experiment with employment of rubrocol in tuberculosis of the peripheral lymphatic glands in children and youths]. PMID- 21008155 TI - [Electrosurgical treatment of lupus of the oral mucosa]. PMID- 21008156 TI - [Not Available]. PMID- 21008157 TI - [Not Available]. PMID- 21008158 TI - [Not Available]. PMID- 21008159 TI - [Not Available]. PMID- 21008160 TI - [Not Available]. PMID- 21008161 TI - Study of experimental urinary calculi; methods for producing and preventing calculous formation in the bladder and urethra of albino rats. PMID- 21008162 TI - Study of experimental urinary calculi; quantitative microchemical, spectrographic, and citric acid analyses of albino rat calculi, with a preliminary apatite report. PMID- 21008163 TI - Renal calculi associated with hyperparathyroidism. PMID- 21008164 TI - The significance of spontaneous hematuria associated with hypertrophy of the prostate. PMID- 21008165 TI - Bilateral orchiectomy in advanced or recurring carcinoma of the bladder with severe subjective symptoms; a preliminary report. PMID- 21008166 TI - Treatment of orchitis of mumps. PMID- 21008167 TI - Repair of complete tear of the membranous urethra; case report and suggested new technique for operation. PMID- 21008168 TI - Reiter's syndrome. PMID- 21008170 TI - The transport of spermatozoa in the female reproductive tract. PMID- 21008169 TI - A technique for the assay hyaluronidase in human semen and its correlation with the sperm concentration. PMID- 21008171 TI - Report of U.S. Public Health Service Advisory Committee on public education for the prevention of venereal diseases, July 18, 1945. PMID- 21008172 TI - Syphilis among civilians during World War II, January 1, 1942, through June 30, 1943. PMID- 21008173 TI - The crossroads of veterinary and human medicine. PMID- 21008174 TI - Further observations on canine Leptospirosis in Antigua, B.W.I. PMID- 21008175 TI - Observation on the incidence of the common stomach worm, Haemonchus contortus, in young cattle in a Montreal abattoir. PMID- 21008178 TI - Veterinary work in Shanghai, China. PMID- 21008177 TI - Studies in pullorum disease; transmission of infection to healthy birds by contact. PMID- 21008176 TI - Observations on the permeability of the lactating bovine mammary gland to penicillin. PMID- 21008179 TI - How may the incidence of tuberculosis in hogs be reduced. PMID- 21008180 TI - Additional outbreaks of equine encephalomyelitis in New Jersey pheasants. PMID- 21008181 TI - Veterinary activities with animals at a port of embarkation. PMID- 21008182 TI - CASE of intersexuality (hermaphrodism) in a horned goat. PMID- 21008183 TI - Canine tuberculosis; a report of the first case officially diagnosed and confirmed in Puerto Rico. PMID- 21008184 TI - Swine coccidiosis in Venezuela. PMID- 21008185 TI - LEISHMANIASIS (kala-azar) of dogs. PMID- 21008186 TI - DDT; toxicity and indications. PMID- 21008187 TI - INFECTIOUS pleuropneumonia of the goat. PMID- 21008188 TI - WORK of the Army veterinary services in relation to military dairy farms in India. PMID- 21008189 TI - CASE of phosphorus burns in the dairy cow. PMID- 21008190 TI - Hydatid cysts in the horse. PMID- 21008191 TI - No. 3 Veterinary Hospital and after. PMID- 21008192 TI - An investigation into an outbreak of acute nephritis. PMID- 21008193 TI - Artificial breeding of dairy cattle as a practical procedure for the general practitioner. PMID- 21008194 TI - On the etiology of abscesses in goats. PMID- 21008195 TI - Teniacidal action of di-phenthane-70. PMID- 21008196 TI - A method for studying numerical and topographic problems in the whole femoral marrow of rats and guinea pigs, with the use of undecalcified sections. PMID- 21008197 TI - The vital necessity of adrenal cortical tissue in a mammal and the effects of proliferation of cortical cells from dormant coelomic mesothelium. PMID- 21008198 TI - Mitotic division and degeneration of lymphocytes within the cells of intestinal epithelium in the mouse. PMID- 21008199 TI - A comparison of the action of extension of the knee and elbow joints in man. PMID- 21008200 TI - Cross-sectional diameters and areas of the human spinal cord. PMID- 21008201 TI - The motion of the migrating cells in tissue cultures of lymph nodes. PMID- 21008202 TI - [Not Available]. PMID- 21008203 TI - [Not Available]. PMID- 21008204 TI - The nutritional requirements of the lactic acid bacteria and their application to biochemical research. PMID- 21008205 TI - The interrelationship of iron and certain accessory factors in the growth of Rhizobium trifolii, strain 205. PMID- 21008206 TI - The pyrogenicity of bacterial contaminants found in biologic products. PMID- 21008207 TI - Studies on the death of bacteria at low temperature; the influence of the intensity of the freezing temperature, repeated fluctuations of temperature, and the period of exposure to freezing temperatures on the mortality of Escherichia coli. PMID- 21008208 TI - Morphology and nature of the pleuropneumonia group of organisms. PMID- 21008210 TI - The influence of changes in concentration and temperature upon the bactericidal activity of formaldehyde in aqueous solutions. PMID- 21008209 TI - The paperdisc agar-plate method for the assay of antibiotic substances. PMID- 21008211 TI - The fermentation of glucose by certain gram-positive, nonsporeforming, anaerobic bacteria. PMID- 21008212 TI - Correlation between antibacterial power and chemical structure of higher alkyl ammonium ions. PMID- 21008213 TI - Entomology in malaria control. PMID- 21008214 TI - Insect damage to nylon. PMID- 21008215 TI - Some dinitrophenol derivatives as mosquito larvicides. PMID- 21008217 TI - DDT compared with other insecticides for control of hemipterous insects on cotton. PMID- 21008216 TI - The transport of insects in aircraft. PMID- 21008218 TI - DDT for bollworn control during 1944. PMID- 21008219 TI - DDT as a culicine larvicide. PMID- 21008220 TI - DDT dispersed from airplanes for control of adult mosquitoes. PMID- 21008221 TI - DDT-oil sprays applied from an airplane to control Anopheles and Mansonia mosquitoes. PMID- 21008222 TI - DDT surface sprays for control of stablefly breeding in shore deposits of marine grass. PMID- 21008223 TI - DDT to control ticks on vegetation. PMID- 21008224 TI - DDT and rotenone used in oil to control the California red scale. PMID- 21008225 TI - DDT and other insecticides to control the Saratoga spittle insect on jack pine. PMID- 21008226 TI - Laboratory studies with rotenone oil in sprays to control the California red scale. PMID- 21008227 TI - New insecticides for chicken lice control. PMID- 21008228 TI - Food preferences of the firebrat. PMID- 21008229 TI - Insect pathology and biological control. PMID- 21008230 TI - The bloodsucking habits and growth of nymphs of Triatoma gerstaeckeri. PMID- 21008231 TI - Insecticides for control of the cotton flea hopper. PMID- 21008232 TI - DDT for control of the grape bud beetle. PMID- 21008233 TI - Control of housefly breeding in partly digested sewage sludge. PMID- 21008234 TI - Thanite as a control for ants. PMID- 21008235 TI - Factors inducing diapause in the Oriental fruit moth. PMID- 21008236 TI - DDT and bedbugs in chicken houses. PMID- 21008237 TI - The effect on the fingers of the poison of Formica exsectoides. PMID- 21008238 TI - DDT residual spray tests in Panama. PMID- 21008239 TI - DDT and control of honeybees. PMID- 21008240 TI - Methyl bromide for control of the pineapple mealybug. PMID- 21008241 TI - Dusting for cattle lice. PMID- 21008242 TI - DDT for the control of goat lice. PMID- 21008244 TI - DDT for the tent caterpillar. PMID- 21008243 TI - Mosquitoes of northwest Florida. PMID- 21008245 TI - Sorption of HCN by insect pupae. PMID- 21008246 TI - DDT-like effects from injection of other compounds into roaches. PMID- 21008247 TI - Natural heteroagglutinins in the serum of the spiny lobster, Panulirus interruptus; chemical and antigenic relation to blood proteins. PMID- 21008249 TI - Studies on fresh-water Bryozoa; Fredericella australiensis var. browni, n. var. PMID- 21008248 TI - Studies on marine Bryozoa; Aeverrillia setigera (Hincks) 1887. PMID- 21008250 TI - Studies on the biochemistry of tetrahymena; riboflavin, pantothen, biotin, niacin and pyridoxine in the growth of T. geleii W. PMID- 21008251 TI - The structure of meiotic chromosomes in the grasshopper and its bearing on the nature of chromomeres and lamp-brush chromosomes. PMID- 21008252 TI - [The sun, life and chlorophyll]. PMID- 21008253 TI - [On the role of aminoacids in animal bodies]. PMID- 21008254 TI - [The blood and its substitutes]. PMID- 21008255 TI - [The present state of the problem of endocrine gland transplantation]. PMID- 21008256 TI - [Modern advances in pollinistics and the evolution of higher plants]. PMID- 21008257 TI - [Homotransplantation of the frog heart]. PMID- 21008258 TI - [Parthenogenetic females among certain races of the honey bee]. PMID- 21008260 TI - [The biochemistry of muscle training]. PMID- 21008259 TI - [The automatism and reflex in the activity of the respiratory centre of vertebrates]. PMID- 21008261 TI - [Blood plasma proteins and their role in metabolic processes in the organism]. PMID- 21008262 TI - [New data concerning the nature of mammary gland malignant tumors]. PMID- 21008263 TI - [Antagonistic substances and bacteria control in animals and plants]. PMID- 21008264 TI - [Contribution to the history of the discovery by I.M. Setchenov of central inhibition]. PMID- 21008265 TI - [The ecological coefficient as a new measure of the influence of external factors upon animals and men]. PMID- 21008266 TI - [On the interaction of genes and cytoplasm in development and heredity]. PMID- 21008267 TI - The carcinogenicity of p-dimethylaminoazobenzene in diets containing the fatty acids of hydrogenated coconut oil or of corn oil. PMID- 21008268 TI - Certain effects of dietary fats on the production of liver tumors in rats fed p dimethylaminoazobenzene. PMID- 21008269 TI - Desoxyribonucleic acid in epidermal carcinogenesis induced by methylcholanthrene. PMID- 21008270 TI - Observations on experimentally produced sarcomas of pigeons. PMID- 21008271 TI - Effects of ultraviolet radiation on 3,4-benzpyrene and other polycyclic aromatic hydrocarbons; absorption spectra and some chemical properties of the water soluble products. PMID- 21008272 TI - Effects of ultraviolet radiation on 3,4-benzpyrene and other polycyclic aromatic hydrocarbons; the role of benzene in the photoreactions in solutions containing it. PMID- 21008273 TI - Effects of ultraviolet radiation on 3,4-benzpyrene and other polycyclic aromatic hydrocarbons; carcinogenic activity of aqueous extracts from irradiated 3,4 benzpyrene. PMID- 21008275 TI - Electrocardiographic changes in early syphilis prior to and upon completion of intensive arsenotherapy. PMID- 21008276 TI - Studies concerning the etiology and pathogenesis of neurocirculatory asthenia; the respiratory manifestations of neurocirculatory asthenia. PMID- 21008274 TI - The effect of smoking cigarettes on the peripheral blood flow in subjects in the older age group with coronary arteriosclerosis and hypertension. PMID- 21008277 TI - Cardiac aneurysm with spontaneous rupture; report of two cases. PMID- 21008278 TI - The relative incidence of rheumatic valve disease in New York and Costa Rica and its bearing on the rheumatic origin of calcareous aortic stenosis. PMID- 21008279 TI - The electrocardiogram in pneumoperitoneum. PMID- 21008280 TI - The relation of age and other factors to cardiac subendothelial hemorrhage in dogs. PMID- 21008281 TI - Angina pectoris with particular reference to its occurrence before and after myocardial infarction. PMID- 21008282 TI - Facts and fallacies about the normal apex beat. PMID- 21008283 TI - Periarteritis nodosa; report of case. PMID- 21008284 TI - Complete A-V block in a fetus, case report. PMID- 21008285 TI - Annulus fibrosus calcification of the mitral valve. PMID- 21008286 TI - Contusion of the heart. PMID- 21008287 TI - Mercurial diuretics; intolerance as shown by skin sensitivity. PMID- 21008288 TI - The effect of emetine on the heart. PMID- 21008289 TI - The carotid shudder. PMID- 21008290 TI - A quantitative electrocardiographic method. PMID- 21008292 TI - Paroxyamal tachycardia and 2:1 heart block. PMID- 21008291 TI - A case of myxoma of the heart. PMID- 21008293 TI - Immersion as a factor in the development of hypertension. PMID- 21008294 TI - Experimental auricular fibrillation. PMID- 21008295 TI - Disease of the pericardium. PMID- 21008296 TI - Rheumatic disease of the pericardium. PMID- 21008297 TI - The electrocardiogram of pericardial disease. PMID- 21008298 TI - Human biotin metabolism on various levels of biotin intake. PMID- 21008299 TI - Liver arginase; preparation of extracts of high potency, chemical properties, activation-inhibitation, and pH-activity. PMID- 21008300 TI - Liver arginase; kinetic properties. PMID- 21008301 TI - Penicillin; penicillinase. PMID- 21008302 TI - The activation of papain and related plant enzymes with sodium thiosulfate. PMID- 21008304 TI - Factors influencing the destructive effects of acidic beverages on the teeth of white rats and hamsters. PMID- 21008303 TI - The effect of tocopherol and of fat on the resistance of rats to anoxic anoxia. PMID- 21008305 TI - Preparation of the egg yolk lipoprotein, lipovitellin. PMID- 21008306 TI - Estimation of blood in tissue. PMID- 21008307 TI - The occurrence and estimation of phytofluene in plants. PMID- 21008308 TI - Granulocytopenia and anemia in riboflavin-deficient rats and treatment with L. casei factor (folic acid) and riboflavin. PMID- 21008309 TI - The inactivation of iron by 2,2'-bipyridine and its effect on riboflavin synthesis by Clostridium acetobutylicum. PMID- 21008310 TI - Infection by viruses. PMID- 21008311 TI - Centrifugation. PMID- 21008312 TI - Molecular distillation. PMID- 21008313 TI - Modifying the viscosity of sulfur. PMID- 21008314 TI - Kinetics of sucrose crystallization; sucrose/nonsucrose solutions. PMID- 21008315 TI - Vitamin retention in processed meat; effect of storage. PMID- 21008316 TI - Nitrogenous constituents of flaxseed; peptization. PMID- 21008317 TI - Storage of dried fruit; influence of moisture and sulfur dioxide on deterioration of apricots. PMID- 21008318 TI - Physical, chemical and immunological properties of phosphorylated crystalline horse serum albumin. PMID- 21008319 TI - Proportion of ester anion and amide from esters and sodium amide; carbonation of esters; synthesis of malonic acid derivatives. PMID- 21008320 TI - Streptomyces antibiotics; hydrolytic cleavage of streptomycin to streptidine. PMID- 21008321 TI - Derivatives of 6-methoxy-8-aminoquinoline. PMID- 21008322 TI - Reaction of formaldehyde with proteins; participation of the guanidyl groups and evidence of crosslinking. PMID- 21008323 TI - The polymorphism of sulfapyridine. PMID- 21008324 TI - Studies in chemotherapy; some sulfanilamidoheterocycles. PMID- 21008325 TI - Synthesis of antimalarials; the synthesis of certain compounds related to quinacrine. PMID- 21008326 TI - The splitting of human gamma globulin antibodies by papain and bromelin. PMID- 21008327 TI - Some 7-substituted 4-aminoquinoline derivatives. PMID- 21008328 TI - The condensation of pyruvic acid and formamide. PMID- 21008329 TI - The role of neighboring groups in replacement reactions; the reaction of stilbene dichlorides with silver acetate. PMID- 21008331 TI - Quinolines; the synthesis of 8-substituted 3-methyl-4-(1'-methyl-4' diethylaminobutylamino)-quinolines. PMID- 21008330 TI - QUINOLINES; the synthesis of 3-methyl-4-(1'methyl-4'-diethylaminobutylamino) quinoline and some 6-substituted derivatives. PMID- 21008332 TI - A study of the behavior of dextrose sodium chloride in hydrochloric acid solutions. PMID- 21008333 TI - Bromine analogs of DDT. PMID- 21008334 TI - Observations on the equilibrium between cis- and transstilbene. PMID- 21008335 TI - Stability of DDT and related compounds. PMID- 21008336 TI - The synthesis of d1-methionine. PMID- 21008338 TI - 6'-methoxy-8-oximino-3-propyl-rubatoxanone. PMID- 21008337 TI - A dimorphic form of d-catechin. PMID- 21008339 TI - A new synthesis of 7,8-diaminoquinoline. PMID- 21008340 TI - Penicillin yields from new mold strains. PMID- 21008342 TI - Sulphonamides; the action of amines on ethyl 4-sulphanilamidobenzoate; some alternative preparative methods for sulphanilamidobenzamides. PMID- 21008341 TI - Sulphonamides; the action of ammonia on sulphanilamidobenzoic esters in the light of the general theory of ester ammonolysis. PMID- 21008343 TI - The quantitative estimation of xylose. PMID- 21008344 TI - The chemistry of gum tragacanth; tragacanthic acid. PMID- 21008345 TI - The chemistry of gum tragacanth; derivatives of d- and l-fucose. PMID- 21008346 TI - Absorption spectra of acridines; the hydroxyacridines. PMID- 21008347 TI - Studies in the detoxication of catalyst poisons; the detoxication of cystein with metallic per-acids. PMID- 21008348 TI - Contributions to the chemistry of synthetic antimalarials; some delta diethylamino-alpha-methylbutylamino derivatives of pyridine and thiazole. PMID- 21008349 TI - The capsular polysaccharide of rhizobium radicicolum. PMID- 21008350 TI - The interconversion of iron oxides and sulphides. PMID- 21008351 TI - New potential chemotherapeutic agents; derivatives of aminoquinoxalines. PMID- 21008352 TI - A preliminary study of the polyuronide hemicellulose of Phormium tenax (N.Z.flax). PMID- 21008353 TI - Structure of compounds of ferrocyanide type; crystal structure of hexamethylisocyanidoferrous chloride. PMID- 21008355 TI - Mesohydric tautomerism. PMID- 21008354 TI - Some derivatives of 1:1:1-trichloro-2: 2-di (4-chlorophenyl) ethane (DDT). PMID- 21008356 TI - The action of methanol on phenol in the presence of alumina; formation of anisole, methylated phenols, and hexamethylbenzene. PMID- 21008357 TI - New potential chemotherapeutic agents; derivatives of 2-amino-benzocinnoline. PMID- 21008358 TI - Synthesis of diamino sulphones. PMID- 21008359 TI - Derivatives of l-azanthraquinone. PMID- 21008360 TI - The union of gaseous oxygen with methyl oleate, linoleate, and linolenate. PMID- 21008361 TI - The preparation of some 2:3-naphthalene derivatives. PMID- 21008362 TI - A review of the clinical and roentgenologic manifestations of incipient periodontal disease. PMID- 21008363 TI - Local acidity; a cause of dental erosion-abrasion; progress report of the Erosion Abrasion Committee of the New York Academy of Dentistry. PMID- 21008364 TI - Numbness of lips, tongue and face. PMID- 21008365 TI - Thrush (monilia albicans). PMID- 21008366 TI - Autonomy in dental education. PMID- 21008367 TI - The plan of Columbia University, aimed to improve the training of dentists. PMID- 21008368 TI - PROPOSAL to convert the School of Dental and Oral Surgery into a Department of Dentistry of the Medical School. PMID- 21008369 TI - Acceleration of the setting of zinc oxide cements. PMID- 21008371 TI - The spring bridge. PMID- 21008370 TI - Advance in the construction and use of splints in the treatment of fractures of the jaws. PMID- 21008373 TI - Restoration of fractured incisors in children. PMID- 21008372 TI - A case of cerebral anoxaemia occurring as the result of anoxia during the administration of sodium pentothal. PMID- 21008375 TI - The use of the central bearing point for balancing full upper and lower dentures. PMID- 21008374 TI - Surgery of the torus palatinus. PMID- 21008376 TI - The conservative treatment of hypertrophic gingivitis. PMID- 21008377 TI - An allantoin-sulfathiazole combination in treating Vincent's infection. PMID- 21008378 TI - Case report of trifacial pain caused by a dentigerous cyst. PMID- 21008379 TI - The aetiology of Vincent's gingivitis. PMID- 21008380 TI - A vitallium implant as a bridge abutment. PMID- 21008381 TI - Surgery of the month and jaws. PMID- 21008382 TI - The newer knowledge of hygiene in diet. PMID- 21008383 TI - Nutrition, a field for dental expansion. PMID- 21008384 TI - Some applications of stainless steel in orthodontics. PMID- 21008385 TI - Alternate anchylosis in the teeth of South African snakes. PMID- 21008387 TI - Painless treatment of vital dentin; a practical procedure with warm medicaments. PMID- 21008386 TI - Drugs and prescriptions used in periodontia; their practical application. PMID- 21008388 TI - Postextraction bacteriemia prevented by sulfanilamide. PMID- 21008389 TI - Use and abuse of sulfa drugs. PMID- 21008390 TI - Local application of sulfa drugs following extraction and oral surgery procedures. PMID- 21008391 TI - Sodium fluoride therapy for combating dentin sensitivity and gingival decay. PMID- 21008392 TI - Treatment of mouth infections with sulfathiazole paste. PMID- 21008393 TI - Topical application of sodium fluoride to control dental caries. PMID- 21008394 TI - The use of penicillin by the dental general practitioner; penicillin sulfanilamide cones for topical administration. PMID- 21008395 TI - Penicillin and tyrothricin therapy in relation to dentistry and oral surgery. PMID- 21008396 TI - Pressure anesthesia of the dental pulp, with procaine-penicillin paste. PMID- 21008397 TI - A review of 510 complete dental examination records. PMID- 21008398 TI - Infected, impacted teeth. PMID- 21008399 TI - PENICILLIN and sulfonamides. PMID- 21008400 TI - CHROMIC acid leading choice for Vincent's infection therapy. PMID- 21008401 TI - Dentistry in Norway. PMID- 21008402 TI - The organic constituent of enamel. PMID- 21008403 TI - Aerodontalgia. PMID- 21008404 TI - The electric pulp tester in oral diagnosis. PMID- 21008405 TI - The dental bacterial plague and its role in the caries process. PMID- 21008406 TI - Radioactive isotopes and their use in studying the metabolism of the calcified structures of the teeth. PMID- 21008408 TI - The temperature verification test in serology. PMID- 21008407 TI - The estimation of polyvinyl alcohols in body fluids. PMID- 21008409 TI - Histological technic. PMID- 21008410 TI - The electron microscope. PMID- 21008411 TI - Diets and food items for the experimental production of thiamin deficiency in man. PMID- 21008412 TI - Nutrients consumed by Army students at the University of Missouri. PMID- 21008413 TI - Ascorbic acid content of food served in a cooperative residence hall for women. PMID- 21008414 TI - Dietary study of Cornell University women. PMID- 21008415 TI - Effect of quantity preparation procedures on vitamin retention; canned tomatoes. PMID- 21008416 TI - The administrative dietitian in industrial feeding. PMID- 21008417 TI - EDUCATIONAL qualifications of nutritionists in health agencies. PMID- 21008418 TI - Nicotinic acid and the level of protein intake in the nutrition of the pig. PMID- 21008419 TI - The therapeutic effect of yeast and pyridoxine on poikilocytosis in dairy cattle. PMID- 21008420 TI - Field illumination and commercial handling as factors in determining the ascorbic acid content of tomatoes received at the cannery. PMID- 21008421 TI - The effect of manufacturing methods on the ascorbic acid content and consistency characteristics of tomato juice. PMID- 21008422 TI - The elimination and distribution of selenium in the tissues in experimental selenium poisoning. PMID- 21008423 TI - Secretion of vitamin D in milks of women fed fish liver oil. PMID- 21008424 TI - Vitamin A requirements in calves. PMID- 21008425 TI - The influence of ascorbic acid on the activity of gonadotropic hormones in guinea pigs. PMID- 21008426 TI - The availability of the iron in Hawaiian grown vegetables. PMID- 21008427 TI - Silent gallstones. PMID- 21008428 TI - Eosinophilia on a gastro-intestinal hospital service; case reports on four patients with a syndrome of eosinophila, leucocytosis and gastro-intestinal complaints. PMID- 21008429 TI - A review of the gastro-enterologic roentgenologic literature for the year 1943. PMID- 21008430 TI - Nutrition in the aged. PMID- 21008431 TI - Enterogastrone, anthelone and urogastrone; a review of the literature and a suggestion for the organization of a national committee for the study of peptic ulcer. PMID- 21008432 TI - Is bile and pancreatic juice a factor in the genesis of ulcerative colitis? an experimental study. PMID- 21008433 TI - On the physiology of volatile fatty acids. PMID- 21008434 TI - PUZZLING attacks of indigestion due to a latent infection with a cold virus. PMID- 21008435 TI - Diet and the teeth. PMID- 21008436 TI - Pattern reversal in the plumage of thiouracil-treated hybrid fowl. PMID- 21008437 TI - A seedling method for testing aphid resistance, and its application to breeding and inheritance studies in cucurbits and other plants. PMID- 21008438 TI - FAMILY allowances in Canada. PMID- 21008439 TI - Evaluation of species crosses of cattle by polyallel crossing; a study of zebu and Africander X Aberdeen-Angus cattle under subtropical conditions. PMID- 21008440 TI - A dactylolysis mutation in the fowl. PMID- 21008441 TI - Art and mental disease. PMID- 21008442 TI - Artistic behavior of the mentally deranged. PMID- 21008443 TI - The art of schizophrenics. PMID- 21008444 TI - Great artists who suffered from mental disorders. PMID- 21008446 TI - On the catalog card for a rare book. PMID- 21008445 TI - Analysis of Government records an emerging profession. PMID- 21008447 TI - Uniform statistics for library holdings. PMID- 21008448 TI - A guide to radiographic interpretation of esophageal and gastric disorders. PMID- 21008450 TI - The effect upon health of restrictions of the motility of the lower bowel. PMID- 21008449 TI - Continuous caudal analgesia during labor and delivery; a report of 750 cases. PMID- 21008451 TI - Foreign bodies in the nasal passages. PMID- 21008452 TI - MODERN nurses home at Queen Charlotte's Maternity Hospital, London. PMID- 21008453 TI - OAK RIDGE HOSPITAL: high-speed development of hospital facilities for atomic bomb workers. PMID- 21008454 TI - Some notes on water treatment. PMID- 21008455 TI - Consents to operations and other surgical procedures; patients other than mental or mental deficiency cases. PMID- 21008458 TI - President Truman's proposed national health program in Perspective. PMID- 21008457 TI - PROGRESS in veterans' relations through new methods. PMID- 21008456 TI - The key to emergency care is cooperation. PMID- 21008459 TI - Administration of an effective pharmacy requires a sound policy. PMID- 21008460 TI - Convalescent care; a neglected factor? PMID- 21008461 TI - A program to step up the autopsy rate is essential. PMID- 21008462 TI - FULL text of S. 191, as adopted by the United States Senate. PMID- 21008463 TI - Preliminary report on the use of tantalum oxide, Type 400. PMID- 21008465 TI - Industrial health in small plants. PMID- 21008464 TI - Rates of absenteeism and turnover in personnel in relation to employees' work attitudes. PMID- 21008466 TI - A discussion of the commoner industrial dermatoses. PMID- 21008467 TI - Alphatron radon ointment in industrial practice. PMID- 21008468 TI - Industrial medical services. PMID- 21008469 TI - Controlled industrial sanitation. PMID- 21008470 TI - Industrial dentistry. PMID- 21008471 TI - Organization and operation of the industrial diagnostic service of the Chicago Dental Society. PMID- 21008472 TI - Progress of a dental program. PMID- 21008473 TI - [Not Available]. PMID- 21008474 TI - [Not Available]. PMID- 21008475 TI - [Not Available]. PMID- 21008477 TI - [Not Available]. PMID- 21008476 TI - [Not Available]. PMID- 21008478 TI - [Not Available]. PMID- 21008479 TI - [Not Available]. PMID- 21008480 TI - The differential diagnosis of bovine brucellosis from the bactericidal action of blood plasma. PMID- 21008481 TI - [Not Available]. PMID- 21008482 TI - [Not Available]. PMID- 21008483 TI - [Not Available]. PMID- 21008484 TI - [Not Available]. PMID- 21008485 TI - [Not Available]. PMID- 21008486 TI - [Not Available]. PMID- 21008487 TI - [Not Available]. PMID- 21008488 TI - [Not Available]. PMID- 21008489 TI - [Not Available]. PMID- 21008490 TI - [Not Available]. PMID- 21008491 TI - [Not Available]. PMID- 21008492 TI - [Not Available]. PMID- 21008493 TI - [Not Available]. PMID- 21008494 TI - Esophageal lesions associated with acrosclerosis and scleroderma. PMID- 21008495 TI - Neurologic complications during meningococcic meningitis treated with sulfonamide drugs. PMID- 21008496 TI - An account of stock. PMID- 21008497 TI - Absence of electrocardiographic changes in Tsutsugamushi fever (scrub typhus); report of two hundred consecutive cases. PMID- 21008498 TI - South American trypanosomiasis (Chagas' disease). PMID- 21008499 TI - Sickle cell anemia in white patients with ulcers of the ankles; report of two cases. PMID- 21008500 TI - Clinical syndrome in patients with pulmonary embolism. PMID- 21008501 TI - Blood; a review of the recent literature. PMID- 21008503 TI - [Not Available]. PMID- 21008502 TI - [Not Available]. PMID- 21008504 TI - [Not Available]. PMID- 21008505 TI - [Not Available]. PMID- 21008506 TI - [Not Available]. PMID- 21008507 TI - [Not Available]. PMID- 21008508 TI - [Basic problems of experimental oncology]. PMID- 21008509 TI - [Contribution to the role of heredity in the etiology of cancer]. PMID- 21008510 TI - [On the quantitative distribution of cancerogeneous hydrocarbons in an animal organism]. PMID- 21008511 TI - [Some data on the question of transplantability of malignant tumors of organs of a blastomatous animal]. PMID- 21008512 TI - [On the transplantation of mouse sarcoma by the liver of a blastomatous animal]. PMID- 21008514 TI - [Morphological changes of the liver in experimental ileus]. PMID- 21008515 TI - [Morphological changes of the blood and blood forming apparatus under action of UHF currents]. PMID- 21008513 TI - [The morbid morphology of man brucellosis]. PMID- 21008516 TI - [The changes of the nervous elements of the skin and some other organs in typhus exanthematicus]. PMID- 21008517 TI - [Reactive changes of the motor nervous endings of the skeletal muscle in experimental ischemia]. PMID- 21008518 TI - [Experimental nephritic hypertony in dogs]. PMID- 21008519 TI - [New ways of epilepsy diagnosis]. PMID- 21008520 TI - [A peculiarity of insulin shock aggravated by C avitaminosis]. PMID- 21008521 TI - [The mechanism of the action of synatren]. PMID- 21008522 TI - [Oxidation-reduction processes occurring in the mucosa of the stomach in connection with secretion; first communication; the effect of food irritator]. PMID- 21008523 TI - [On the biological role of the salts of the elements present in the organism in minimum quantities; contribution to the role of fluor on hydrocarbon metabolism]. PMID- 21008524 TI - [Contents of nitrogen in various architectonic formations of the cortex of the brain]. PMID- 21008525 TI - [Desamination of certain amino acids in the organism (angio-chemical examination)]. PMID- 21008526 TI - [Proteinic dissolution of tissue in burns]. PMID- 21008527 TI - [On the role of acetylcholine in the mechanism of the rise of nerve refractoriness]. PMID- 21008528 TI - [The effect of eserin on spinal shock]. PMID- 21008529 TI - [Contribution to the summational and accomodational processes in central inhibition, provoked by the rare electrical irritation of the afferent nerve]. PMID- 21008530 TI - The surgery of arterial disease and injury. PMID- 21008531 TI - Observations on cases of starvation at Belsen. PMID- 21008532 TI - D.B.E.: a new synthetic oestrogen. PMID- 21008533 TI - D.B.E. in treatment of menopausal symptoms. PMID- 21008534 TI - Concentrating malaria parasites in thin films. PMID- 21008535 TI - Immunity to sandfly fever. PMID- 21008536 TI - A case of locked twins. PMID- 21008537 TI - The Herbal of Rufinus. PMID- 21008538 TI - Ocular signs in the prisoner of war returned from the Far East. PMID- 21008539 TI - Paracentesis and myringotomy; a question of terminology. PMID- 21008540 TI - DESIGN and craftsmanship for the tuberculous. PMID- 21008541 TI - Operation for varicose veins. PMID- 21008542 TI - Non-specific mesenteric lymphadenitis. PMID- 21008543 TI - Hospital reforms. PMID- 21008544 TI - [Not Available]. PMID- 21008545 TI - [Not Available]. PMID- 21008546 TI - [Not Available]. PMID- 21008547 TI - [Not Available]. PMID- 21008548 TI - [Not Available]. PMID- 21008549 TI - [Not Available]. PMID- 21008550 TI - [Not Available]. PMID- 21008551 TI - [Not Available]. PMID- 21008552 TI - [Not Available]. PMID- 21008553 TI - [Not Available]. PMID- 21008554 TI - [Not Available]. PMID- 21008555 TI - [Not Available]. PMID- 21008556 TI - [Not Available]. PMID- 21008557 TI - [Not Available]. PMID- 21008558 TI - [Not Available]. PMID- 21008559 TI - [Not Available]. PMID- 21008560 TI - [Not Available]. PMID- 21008561 TI - [Not Available]. PMID- 21008562 TI - [Not Available]. PMID- 21008563 TI - [Not Available]. PMID- 21008564 TI - [Not Available]. PMID- 21008565 TI - [Not Available]. PMID- 21008566 TI - [Not Available]. PMID- 21008567 TI - [Not Available]. PMID- 21008569 TI - [Not Available]. PMID- 21008568 TI - [Not Available]. PMID- 21008570 TI - [Not Available]. PMID- 21008571 TI - Marihuana. PMID- 21008572 TI - The treatment of varicose veins. PMID- 21008573 TI - Placental permeability. PMID- 21008574 TI - Physiologic changes associated with varicose veins and their correction. PMID- 21008575 TI - Functions and connections of the medial lemniscus. PMID- 21008576 TI - Epivascular choroidal pigment streaks, their pathology and possible prognostic significance. PMID- 21008577 TI - The significance of streptococci isolated from the female urinary tract. PMID- 21008578 TI - Clinical and electrocardiographic response to N-methylnicotinamide chloride administration in man. PMID- 21008579 TI - Lipid response to vitamin A administration; a possible test for vitamin A deficiency. PMID- 21008580 TI - Genito-urinary tuberculosis. PMID- 21008581 TI - Solitary systolic murmurs. PMID- 21008582 TI - Typhoid fever. PMID- 21008583 TI - Starving the bacteria; how new drugs are developed. PMID- 21008585 TI - ARTIFICIAL insemination. PMID- 21008584 TI - A case of ulcerative endocarditis treated with sulphadiazine and inductothermy. PMID- 21008586 TI - Cardiotoxin inhibitors. PMID- 21008587 TI - Penicillin therapy of rabbit syphilis. PMID- 21008588 TI - Technique of carotid sinus stimulation. PMID- 21008589 TI - Variations in size of human stomach. PMID- 21008590 TI - Anatomical demonstration of the anovulatory menstrual cycle. PMID- 21008591 TI - Introspection and the orbital cortex. PMID- 21008592 TI - Early public health in California. PMID- 21008594 TI - Recovery and rehabilitation. PMID- 21008593 TI - The development and present status of social security in Canada. PMID- 21008595 TI - Planned health in Saskatchewan. PMID- 21008596 TI - Evaluation of renal function in man. PMID- 21008597 TI - A co-operative group clinic. PMID- 21008598 TI - Some notes on interning. PMID- 21008599 TI - [Not Available]. PMID- 21008600 TI - Student internship in Canadian hospitals. PMID- 21008601 TI - Some practical facts about Salmonella infections. PMID- 21008602 TI - The expansion of the Connecticut Cancer Program. PMID- 21008603 TI - Duplication cyst of the terminal ileum with acute inflammatory reaction; report of a case. PMID- 21008604 TI - Adenocarcinoma of the jejunum arising around polyps. PMID- 21008605 TI - Vitamin D poisoning; hypercalcemia; case report. PMID- 21008606 TI - A plan to augment graduate medical training. PMID- 21008607 TI - Expansion of voluntary group health care progress. PMID- 21008608 TI - The veteran and tuberculosis. PMID- 21008609 TI - Public relations as the doctor's individual responsibility. PMID- 21008610 TI - Suggested school health policies. PMID- 21008611 TI - New law covers registration of laboratories examining milk or milk products. PMID- 21008612 TI - [Not Available]. PMID- 21008613 TI - [Not Available]. PMID- 21008614 TI - [Not Available]. PMID- 21008615 TI - [Not Available]. PMID- 21008617 TI - [Not Available]. PMID- 21008616 TI - [Not Available]. PMID- 21008618 TI - The limits and achievements of modern x-ray tube construction. PMID- 21008619 TI - [Not Available]. PMID- 21008620 TI - [Not Available]. PMID- 21008621 TI - [Not Available]. PMID- 21008622 TI - [Not Available]. PMID- 21008623 TI - [Not Available]. PMID- 21008624 TI - [Not Available]. PMID- 21008625 TI - [Not Available]. PMID- 21008626 TI - [Not Available]. PMID- 21008627 TI - [Not Available]. PMID- 21008628 TI - [Not Available]. PMID- 21008629 TI - [Not Available]. PMID- 21008630 TI - [Not Available]. PMID- 21008631 TI - [Not Available]. PMID- 21008632 TI - [Not Available]. PMID- 21008633 TI - [Caring for mother and child--the most important national objective]. PMID- 21008634 TI - [Physiological system of the connective tissue and antireticular cytotoxic serum of academician A A Bogomeolets]. PMID- 21008635 TI - [Vitamins in medical practice]. PMID- 21008636 TI - [Battle injuries to hands and fingers and their treatment]. PMID- 21008637 TI - [Acute abdomen]. PMID- 21008638 TI - [Quartz lamp and its therapeutic application]. PMID- 21008639 TI - [Organization of work of nursing stuff in an obstetric and gynecologic office providing services to women working in entrprises]. PMID- 21008640 TI - [A simple shaking device for fractional and drip transfusions]. PMID- 21008641 TI - [Care for neurosurgical patients in an uncoscious state]. PMID- 21008642 TI - [Bandaging the wounded to skull with loss of brain substance]. PMID- 21008643 TI - [Treatment of frost bite and burns]. PMID- 21008644 TI - [Pappataci disease]. PMID- 21008645 TI - [Treatment of anthrax]. PMID- 21008646 TI - [Diagnostic problems]. PMID- 21008647 TI - [Not Available]. PMID- 21008648 TI - [Not Available]. PMID- 21008649 TI - [Not Available]. PMID- 21008651 TI - [Not Available]. PMID- 21008650 TI - [Not Available]. PMID- 21008652 TI - Nonspecific reactions in routine blood testing for syphilis. PMID- 21008653 TI - Alkali treatment of methyl alcohol poisoning. PMID- 21008654 TI - The in vitro action of streptomycin on bacteria. PMID- 21008656 TI - Backache. PMID- 21008657 TI - Dyspnea in hemophilia from hemorrhage into larynx. PMID- 21008655 TI - Occurrence of Brucella melitensis in Iowa. PMID- 21008658 TI - Iodized salt for the prophylaxis of endemic goiter. PMID- 21008659 TI - MEDICINE and the changing order. PMID- 21008660 TI - Treatment of mixed infections with penicillin; with special reference to the adjuvant action of parachlorophenol. PMID- 21008661 TI - Chemoprophylaxis and sulfonamide resistant streptococci. PMID- 21008662 TI - The treatment of compound fractures of the femur. PMID- 21008663 TI - Meat in the diet of pregnant women. PMID- 21008664 TI - Reexamination of veterans discharged because of heart disease or hypertension. PMID- 21008665 TI - Isospora hominis infection in man. PMID- 21008666 TI - Brain abscess associated with congenital heart disease; report of a case with complete recovery. PMID- 21008667 TI - DEATHS of physicians in 1945. PMID- 21008669 TI - DRUNKENNESS: probative value of chemical tests showing nonintoxication is question for jury. PMID- 21008668 TI - An early observation on penicillin. PMID- 21008671 TI - The importance of newer methods of examination in early diagnosis of chest diseases. PMID- 21008672 TI - Incompatibility. PMID- 21008670 TI - Gynaecology and obstetrics in the Missionary Medical College Hospital. PMID- 21008673 TI - A health insurance plan for Christians. PMID- 21008674 TI - Twin intra-uterine pregnancy with an ectopic pregnancy complicating osteomalacia. PMID- 21008675 TI - Congenital malformation of the mesentery; a report of two cases. PMID- 21008676 TI - [Not Available]. PMID- 21008677 TI - [Not Available]. PMID- 21008678 TI - [Not Available]. PMID- 21008679 TI - [Not Available]. PMID- 21008681 TI - Medicine in the postwar world. PMID- 21008680 TI - Indiana's health program. PMID- 21008682 TI - Osteomyelitis; treatment by radical saucerization and early skin grafting. PMID- 21008683 TI - The relation between trauma and malignant disease. PMID- 21008684 TI - Lung abscess. PMID- 21008685 TI - Meniere's syndrome. PMID- 21008686 TI - Nursing service needs. PMID- 21008687 TI - Behavior problems and habit disturbances in pre-adolescent children; their meaning and management. PMID- 21008688 TI - Use of penicillin ointment in treatment of impetigo and other conditions of the skin. PMID- 21008689 TI - Syphilis: considerations in diagnosis. PMID- 21008690 TI - The pathology of bismuth poisoning. PMID- 21008691 TI - Arsenical exfoliative dermatitis co-incidental with acute hemorrhagic nephritis; case report. PMID- 21008692 TI - Surgical treatment of inguinal hernia. PMID- 21008693 TI - The evaluation of various case finding procedures in a tuberculosis control program. PMID- 21008694 TI - Further data on the pathogenesis of fibroblastic neoplasms; density ratio of tissue computed by the author's exposure meter method. PMID- 21008695 TI - Lipoid nephrosis; a review of the disease with report of case. PMID- 21008696 TI - Neurosyphilis; its diagnosis and treatment. PMID- 21008697 TI - Clinical experiences in the treatment of low back and sciatic pain associated with disorders of the intervertebral disc. PMID- 21008698 TI - Primary cysts of the omentum. PMID- 21008699 TI - The use of curare (introcostrin) in reducing convulsive effects of tetanus. PMID- 21008700 TI - Common macrocytic anemias. PMID- 21008702 TI - The problem of hypertension. PMID- 21008701 TI - Toxic psychosis due to bromides. PMID- 21008703 TI - Rabies. PMID- 21008704 TI - [Neuropathological syndromes in traumatic damages of the thorax]. PMID- 21008705 TI - [On therapeutic illnesses in gunshot wounds and contusions]. PMID- 21008706 TI - [Analysis of diagnostical errors in discrimination of lung tuberculosis]. PMID- 21008707 TI - [Lung cancer simulating tuberculosis]. PMID- 21008708 TI - [Dynamic spirometry as a method of examination of the functional capacity of the apparatus of blood circulation and respiration in the evaluation of work- and battle-capacity]. PMID- 21008709 TI - [Partial electrocardiogram and IVth abductio in infarcts of the myocardium]. PMID- 21008710 TI - [Roentgenological data on deformations of the gastrointestinal tract in hypertonic disease]. PMID- 21008711 TI - [On employment of medical physical culture in hypertonic disease]. PMID- 21008712 TI - [The rates and dynamics of venous pressure in healthy men]. PMID- 21008713 TI - [The normal figures of venous pressure and some physiological oscillations of it]. PMID- 21008714 TI - [Employment of nicotinic acid in acute hepatitis]. PMID- 21008715 TI - [Pathomorphological deformations in the lungs in the so-called alimentary-toxical aleikia]. PMID- 21008716 TI - [Clinico-diagnostical peculiarities of various forms of dysentery]. PMID- 21008717 TI - [The clinics of the sting of the beetle cara-court]. PMID- 21008718 TI - [The effect of the reduced atmospheric pressure on hemodynamics]. PMID- 21008719 TI - [Phenomenon of auto-agglutination in both hypertonic disease and angiospastic syndrome]. PMID- 21008720 TI - [Contribution to the sulphidinotherapy of estival diarrheas]. PMID- 21008721 TI - [Dynamic observations on the capillaries in stenocardia and infarcts of the myocardium]. PMID- 21008722 TI - [The role of coronary atherosclerosis in the functional disturbance of the coronary blood circulation, in the pathogenesis of the obturatio acuta of the coronal arteries and acute infarctis of the myocardium]. PMID- 21008723 TI - [New problems of the clinical forms, early diagnosis and treatment of tetanus and in particular a local one]. PMID- 21008724 TI - [On indications and technics of removal of gunshot foreign bodies from the heart and pericardium]. PMID- 21008725 TI - [Renal hypertony in a dog (experimental investigation)]. PMID- 21008726 TI - [Some questions of clinics and therapy of poisoning with hibernated corns (so called septic angina or alimentary toxical aleikia)]. PMID- 21008727 TI - [Dynamics of oxygen starvation of the septic sick under treatment with massive doses of streptocide]. PMID- 21008728 TI - [The effect of massive doses of streptocide on the state of the acidous-alkaline balance in septic patients and in healthy men]. PMID- 21008729 TI - [Some data on the state of the cardiovascular system in anaerobic infection]. PMID- 21008730 TI - [Aqueous metabolism in rheumatism; pathogenesis of disturbances of aqueous metabolism in rheumatism]. PMID- 21008732 TI - [Transfusion of the blood of hypertonics and its effect on hematopoesis]. PMID- 21008731 TI - [On hemorrhagic pleuritis in lung cancer]. PMID- 21008733 TI - [Early amyloid nephrosis in complications of war traumae of bone]. PMID- 21008734 TI - [Clinics of strongyloidosis of the lungs]. PMID- 21008735 TI - [On the vegeto-syndromes in war traumae]. PMID- 21008736 TI - [Endocrine system and bronchial asthma]. PMID- 21008737 TI - [New ways in the therapy of syphilis; experiment in the treatment of syphilis with penicillin]. PMID- 21008738 TI - [On the pathogenesis and experimental therapy of trophic ulcers]. PMID- 21008739 TI - [Neuro-tropic factor in hematology]. PMID- 21008740 TI - [Quick's test of the liver in clinics of surgical illnesses]. PMID- 21008742 TI - [Some questions of etiology, pathogenesis and differentiation of various forms of diabetes insipidus]. PMID- 21008741 TI - [On the mechanism of the effect of raw vegetative food on excretion of sterins from the organism]. PMID- 21008743 TI - [The changes of ketonemia in pains and after injection of vitamin B1]. PMID- 21008745 TI - [The blood complement in dysentery]. PMID- 21008744 TI - [Aleukemic syndrome in tuberculous splenomegaly]. PMID- 21008746 TI - [Bilirubin in various forms of icterus under the influence of atropine infusion]. PMID- 21008747 TI - [The course of acute epithelial hepatitis in pregnant women]. PMID- 21008748 TI - [On the chemotherapy of experimental infection by anthrax]. PMID- 21008749 TI - Psychiatric lessons from active service. PMID- 21008750 TI - Comparative effect of sulphonamide and penicillin in pneumonia. PMID- 21008751 TI - Mass radiography. PMID- 21008752 TI - Inguinal hernia; the new muscular internal ring. PMID- 21008753 TI - Thoughts on sprue after experience in India. PMID- 21008754 TI - Infusion into the internal saphenous vein at the ankle. PMID- 21008755 TI - Aseptic necrosis at sites of continuous intramuscular penicillin infusion. PMID- 21008756 TI - THAT FLU vaccine. PMID- 21008757 TI - Incidence of infections in war-time day nurseries. PMID- 21008758 TI - TAKING stock. PMID- 21008759 TI - Prognosis and the patient. PMID- 21008760 TI - A transmissible disease in rats inoculated with material from cases of infective hepatitis. PMID- 21008761 TI - Delimitation of subcortical tumours by direct electrography. PMID- 21008762 TI - Schistosomiasis; intensive treatment with antimony. PMID- 21008763 TI - Treatment of schistosomiasis. PMID- 21008764 TI - Large missile lodged in the face; with minor clinical disturbance. PMID- 21008765 TI - Determination of pathogenicity of tubercle bacilli by their intermediate metabolism. PMID- 21008766 TI - Para-aminosalicylic acid in the treatment of tuberculosis. PMID- 21008767 TI - Prevention of accident and limitation of injury. PMID- 21008768 TI - Biological dangers from atomic fission. PMID- 21008770 TI - MICROFILM and medical literature. PMID- 21008769 TI - Aseptic necrosis after penicillin therapy. PMID- 21008771 TI - Uterine bleeding. PMID- 21008772 TI - Everyday orthopedics. PMID- 21008773 TI - Jaundice in pregnancy. PMID- 21008774 TI - Early post-operative rising. PMID- 21008775 TI - Dissecting aneurysm of the aorta. PMID- 21008776 TI - Sixty years ago and after. PMID- 21008777 TI - [Not Available]. PMID- 21008778 TI - [Not Available]. PMID- 21008779 TI - [Not Available]. PMID- 21008780 TI - [Not Available]. PMID- 21008781 TI - [Not Available]. PMID- 21008782 TI - [Not Available]. PMID- 21008783 TI - [Not Available]. PMID- 21008784 TI - [Not Available]. PMID- 21008785 TI - [Not Available]. PMID- 21008786 TI - [Not Available]. PMID- 21008788 TI - [Not Available]. PMID- 21008787 TI - [Not Available]. PMID- 21008789 TI - [Not Available]. PMID- 21008790 TI - [Not Available]. PMID- 21008791 TI - [Not Available]. PMID- 21008792 TI - [Not Available]. PMID- 21008793 TI - [Not Available]. PMID- 21008794 TI - [Not Available]. PMID- 21008796 TI - [Not Available]. PMID- 21008795 TI - [Not Available]. PMID- 21008797 TI - [Not Available]. PMID- 21008798 TI - [Not Available]. PMID- 21008799 TI - [Not Available]. PMID- 21008800 TI - [Not Available]. PMID- 21008802 TI - AMA Council busy developing National Medical Plan. PMID- 21008801 TI - [Not Available]. PMID- 21008803 TI - CONSIDERING a specialty? PMID- 21008804 TI - Hawley would expand plans providing private medical care for vets. PMID- 21008805 TI - S. 1606. PMID- 21008806 TI - A national health congress. PMID- 21008808 TI - How to assure health legislation that will benefit the people. PMID- 21008807 TI - Sigerist sees Kaiser Plan, Soviet system parts of same pattern. PMID- 21008809 TI - ALTMEYER tells medical society officers only Federal program can succeed. PMID- 21008810 TI - Patent ductus arteriosus. PMID- 21008811 TI - Surgical treatment of patent ductus arteriosus. PMID- 21008812 TI - Hypersensitivity to horse serum. PMID- 21008813 TI - A report of the treatment of seven cases of granuloma venereum with penicillin. PMID- 21008814 TI - The treatment of furunculosis. PMID- 21008815 TI - An epidemic of diarrhoea caused by a new strain of the Salmonella group. PMID- 21008816 TI - Experiences, dangers and sequelae of sulphonamide administration. PMID- 21008817 TI - The evolution of the Huhner test. PMID- 21008818 TI - The frigid wife. PMID- 21008819 TI - Evolution of plastic surgery. PMID- 21008820 TI - Generalized insulin allergy; preliminary report. PMID- 21008821 TI - PREVENTIVE medicine throughout the life span; geriatrics. PMID- 21008822 TI - History of women in medicine. PMID- 21008823 TI - Tropical and subtropical diseases in discharged service men. PMID- 21008824 TI - MEMORANDUM on the teaching of tuberculosis to medical students. PMID- 21008826 TI - Acute infectious gingivostomatitis in children. PMID- 21008825 TI - Amebiasis. PMID- 21008827 TI - Addison's disease. PMID- 21008828 TI - Unusual case of appendicitis; case report. PMID- 21008829 TI - Medical problems of menstruation. PMID- 21008830 TI - Rehabilitation of psychiatric war casualties. PMID- 21008831 TI - Important facts regarding hair. PMID- 21008832 TI - Accent on prescriptions. PMID- 21008834 TI - Cystectomy for carcinoma of the bladder. PMID- 21008833 TI - Jaundice; a method of deciding where surgical treatment should supplement medical care. PMID- 21008835 TI - The more recent approaches to allergy. PMID- 21008836 TI - The management of occipito-posterior positions. PMID- 21008837 TI - Adrenal hemorrhage in the newborn. PMID- 21008838 TI - Carcinoma of the esophagus. PMID- 21008839 TI - Osteomyelitis of the lumbar vertebrae. PMID- 21008840 TI - Putrid empyema. PMID- 21008841 TI - The early diagnosis of minimal pulmonary tuberculosis. PMID- 21008842 TI - Pentothal sodium anesthesia in neurologic surgery. PMID- 21008843 TI - Agranulocytosis following mapharsen therapy; a report of two cases treated with penicillin. PMID- 21008844 TI - Some clinical aspects of social medicine. PMID- 21008845 TI - Normal laboratory values. PMID- 21008846 TI - Papillary adenocarcinoma of head of pancreas, with metastases to common bile duct and lung. PMID- 21008847 TI - METHODS of paying physicians under medical-care plans. PMID- 21008848 TI - A suggested plan for state-wide voluntary health insurance. PMID- 21008849 TI - The practical use of digitals. PMID- 21008850 TI - Meningitis due to Hemophilus influenzae; report of case treated with sulfadiazine, streptomycin, and antiserum, with recovery. PMID- 21008851 TI - Cervical ribs and the scalenus anticus syndrome; a review of the literature and report of a case. PMID- 21008852 TI - The antimycotic effect of diethylstilbestrol. PMID- 21008853 TI - The story of yellow fever. PMID- 21008854 TI - Recent advances in knowledge of the Rh blood factors, with special reference to the clinical applications. PMID- 21008855 TI - ANTIGENS in biological therapy. PMID- 21008856 TI - HELMINTHIASIS. PMID- 21008857 TI - AMINO acids; a new field of usefulness. PMID- 21008858 TI - BARBITURATE intoxication. PMID- 21008859 TI - The scope of neurosurgery. PMID- 21008861 TI - Peripheral neuritis (polyneuritis, mutiple symmetrical peripheral neuritis). PMID- 21008860 TI - Modern views on the etiology and treatment of acute anterior poliomyelitis. PMID- 21008862 TI - Modern views on concussion. PMID- 21008863 TI - Subarachnoid haemorrhage. PMID- 21008864 TI - The acute respiratory catarrhs. PMID- 21008865 TI - Posture. PMID- 21008866 TI - Pregnancy and tuberculosis. PMID- 21008867 TI - The names of new drugs. PMID- 21008868 TI - The early recognition of disease; heart disease. PMID- 21008869 TI - Indications for obstetric forceps. PMID- 21008870 TI - The choice of sulphonamides. PMID- 21008871 TI - Fish and rheumatism. PMID- 21008872 TI - [Not Available]. PMID- 21008873 TI - [Not Available]. PMID- 21008874 TI - [Not Available]. PMID- 21008875 TI - [Not Available]. PMID- 21008876 TI - [Not Available]. PMID- 21008877 TI - [Not Available]. PMID- 21008878 TI - [Not Available]. PMID- 21008879 TI - IRRITACION y tension premenstrual y hormonas del cuerpo luteo. PMID- 21008880 TI - [Not Available]. PMID- 21008881 TI - [Not Available]. PMID- 21008882 TI - [Not Available]. PMID- 21008883 TI - [Not Available]. PMID- 21008884 TI - [Not Available]. PMID- 21008885 TI - [Not Available]. PMID- 21008886 TI - [Not Available]. PMID- 21008887 TI - ESTERILIDAD. PMID- 21008888 TI - [Not Available]. PMID- 21008889 TI - [Not Available]. PMID- 21008890 TI - [Not Available]. PMID- 21008891 TI - [Not Available]. PMID- 21008892 TI - [Not Available]. PMID- 21008893 TI - [Not Available]. PMID- 21008894 TI - [Not Available]. PMID- 21008895 TI - [Not Available]. PMID- 21008896 TI - [Not Available]. PMID- 21008897 TI - [Not Available]. PMID- 21008898 TI - [Not Available]. PMID- 21008899 TI - [Not Available]. PMID- 21008900 TI - [Not Available]. PMID- 21008901 TI - [Not Available]. PMID- 21008902 TI - [Not Available]. PMID- 21008903 TI - [Not Available]. PMID- 21008904 TI - [Not Available]. PMID- 21008905 TI - [Not Available]. PMID- 21008906 TI - [Not Available]. PMID- 21008907 TI - [Not Available]. PMID- 21008908 TI - [Not Available]. PMID- 21008909 TI - [Not Available]. PMID- 21008910 TI - [Not Available]. PMID- 21008911 TI - [Not Available]. PMID- 21008912 TI - [Not Available]. PMID- 21008913 TI - [Not Available]. PMID- 21008914 TI - [Not Available]. PMID- 21008915 TI - [Not Available]. PMID- 21008916 TI - [Not Available]. PMID- 21008918 TI - [Not Available]. PMID- 21008917 TI - [Not Available]. PMID- 21008919 TI - [Not Available]. PMID- 21008920 TI - [Not Available]. PMID- 21008921 TI - [Not Available]. PMID- 21008922 TI - [Not Available]. PMID- 21008923 TI - [Not Available]. PMID- 21008924 TI - [Not Available]. PMID- 21008925 TI - [Not Available]. PMID- 21008926 TI - [Not Available]. PMID- 21008927 TI - [Not Available]. PMID- 21008928 TI - [Not Available]. PMID- 21008929 TI - [Not Available]. PMID- 21008930 TI - [Not Available]. PMID- 21008931 TI - [Not Available]. PMID- 21008932 TI - [Not Available]. PMID- 21008933 TI - [Not Available]. PMID- 21008934 TI - [Not Available]. PMID- 21008935 TI - [Not Available]. PMID- 21008936 TI - [Not Available]. PMID- 21008937 TI - [Not Available]. PMID- 21008938 TI - [Not Available]. PMID- 21008939 TI - [Not Available]. PMID- 21008940 TI - [Not Available]. PMID- 21008941 TI - [Not Available]. PMID- 21008942 TI - [Not Available]. PMID- 21008943 TI - [Not Available]. PMID- 21008944 TI - [Not Available]. PMID- 21008945 TI - [Not Available]. PMID- 21008946 TI - [Not Available]. PMID- 21008947 TI - [Not Available]. PMID- 21008948 TI - [Not Available]. PMID- 21008949 TI - [Not Available]. PMID- 21008950 TI - [Not Available]. PMID- 21008951 TI - [Not Available]. PMID- 21008952 TI - [Not Available]. PMID- 21008953 TI - [Not Available]. PMID- 21008954 TI - [Not Available]. PMID- 21008955 TI - [Not Available]. PMID- 21008956 TI - [Not Available]. PMID- 21008957 TI - [Not Available]. PMID- 21008958 TI - [Not Available]. PMID- 21008959 TI - [Not Available]. PMID- 21008960 TI - [Not Available]. PMID- 21008961 TI - [Not Available]. PMID- 21008962 TI - [Not Available]. PMID- 21008963 TI - [Not Available]. PMID- 21008964 TI - [Not Available]. PMID- 21008965 TI - [Not Available]. PMID- 21008966 TI - [Not Available]. PMID- 21008967 TI - [Not Available]. PMID- 21008968 TI - [Not Available]. PMID- 21008969 TI - [Not Available]. PMID- 21008970 TI - [Not Available]. PMID- 21008971 TI - [Not Available]. PMID- 21008972 TI - [Not Available]. PMID- 21008973 TI - [Not Available]. PMID- 21008974 TI - [Not Available]. PMID- 21008975 TI - [Not Available]. PMID- 21008976 TI - [Not Available]. PMID- 21008977 TI - [Not Available]. PMID- 21008978 TI - [Not Available]. PMID- 21008979 TI - [Not Available]. PMID- 21008980 TI - [Not Available]. PMID- 21008981 TI - [Not Available]. PMID- 21008982 TI - [Not Available]. PMID- 21008983 TI - [Not Available]. PMID- 21008984 TI - [Not Available]. PMID- 21008985 TI - [Not Available]. PMID- 21008986 TI - [Not Available]. PMID- 21008987 TI - [Not Available]. PMID- 21008988 TI - [Not Available]. PMID- 21008989 TI - [Not Available]. PMID- 21008990 TI - [Not Available]. PMID- 21008991 TI - [Not Available]. PMID- 21008992 TI - [Not Available]. PMID- 21008994 TI - [Not Available]. PMID- 21008993 TI - [Not Available]. PMID- 21008995 TI - [Not Available]. PMID- 21008996 TI - [Not Available]. PMID- 21008997 TI - [Not Available]. PMID- 21008998 TI - [Not Available]. PMID- 21008999 TI - [Not Available]. PMID- 21009000 TI - [Not Available]. PMID- 21009001 TI - [Not Available]. PMID- 21009002 TI - The evaluation of palpitation. PMID- 21009003 TI - Human encephalitis due to the Western equine encephalomyelitis virus. PMID- 21009004 TI - Lymphosarcoma, with primary manifestations in the gastro-intestinal tract; report of seven cases studied roentgenologically. PMID- 21009005 TI - Physiologic approach to the problem of oophorectomy. PMID- 21009006 TI - Parathyroid adenoma of the anterior mediastinum. PMID- 21009007 TI - Acute meningococcemia without meningitis; report of a case. PMID- 21009008 TI - Vital statistics in public health. PMID- 21009010 TI - [Not Available]. PMID- 21009009 TI - Governing a health unit; organization, activities, and plans for future housing. PMID- 21009011 TI - [Not Available]. PMID- 21009012 TI - [Not Available]. PMID- 21009013 TI - [Not Available]. PMID- 21009014 TI - [Not Available]. PMID- 21009015 TI - [Not Available]. PMID- 21009016 TI - [Not Available]. PMID- 21009017 TI - [Not Available]. PMID- 21009018 TI - [Not Available]. PMID- 21009019 TI - [Not Available]. PMID- 21009020 TI - [Not Available]. PMID- 21009021 TI - [Not Available]. PMID- 21009022 TI - [Not Available]. PMID- 21009023 TI - [Not Available]. PMID- 21009024 TI - [Not Available]. PMID- 21009025 TI - [Not Available]. PMID- 21009026 TI - [Not Available]. PMID- 21009027 TI - [Not Available]. PMID- 21009028 TI - [Not Available]. PMID- 21009029 TI - [Not Available]. PMID- 21009030 TI - [Not Available]. PMID- 21009031 TI - [Not Available]. PMID- 21009032 TI - [Not Available]. PMID- 21009033 TI - [Not Available]. PMID- 21009034 TI - [Not Available]. PMID- 21009035 TI - [Not Available]. PMID- 21009036 TI - [Not Available]. PMID- 21009037 TI - Prostatic carcinoma treated by orchectomy; a third report based on seventy-five cases observed for at least thirty-five months following orchectomy. PMID- 21009038 TI - Bronchial-Asthma. PMID- 21009039 TI - [Not Available]. PMID- 21009040 TI - [Not Available]. PMID- 21009041 TI - Management of thrombophlebitis. PMID- 21009043 TI - Pitfalls in localizing intestinal obstruction with the scout film; case report. PMID- 21009042 TI - A note on the occurrence of silicosis in bituminous coal miners. PMID- 21009044 TI - Occupational therapy and the ageing person. PMID- 21009045 TI - Leukemia in naval personnel. PMID- 21009046 TI - Early recognition and treatment of vascular injuries. PMID- 21009047 TI - Early treatment of orthopedic casualties on a hospital ship. PMID- 21009048 TI - Covering the guillotined stump. PMID- 21009049 TI - Anesthesia on a hospital ship. PMID- 21009050 TI - Medical problems of an internist on a hospital ship. PMID- 21009051 TI - Perforating wounds of the kidney. PMID- 21009052 TI - Punctate cerebral hemorrhage following thoracic trauma. PMID- 21009053 TI - Injuries of the face and neck in war casualties. PMID- 21009054 TI - Eye injuries in war casualties aboard a hospital ship. PMID- 21009055 TI - Embarkation and disembarkation of hospital ship patients. PMID- 21009056 TI - Pneumoroentgenarthrography as a diagnostic aid in internal derangements of the knee. PMID- 21009057 TI - Effect of bite-wing roentgenograms on Navy dental examination findings. PMID- 21009058 TI - Seventy-eight hundred scarlet fever patients. PMID- 21009059 TI - Convalescent serum and pooled plasma in communicable diseases. PMID- 21009060 TI - Penicillin in intrapleural infection. PMID- 21009061 TI - Dermoid cyst of rectovaginal septum. PMID- 21009062 TI - Poisonous snake (habu) bites. PMID- 21009063 TI - Acute appendicitis in amebic dysentery; report of a case. PMID- 21009064 TI - Alveolar resorption due to occupational trauma; report of a case. PMID- 21009065 TI - Simple management of open bite; report of a case. PMID- 21009066 TI - Double gallbladder; report of a case. PMID- 21009067 TI - Casualty handling on an attack transport. PMID- 21009068 TI - Small type skeletal traction apparatus. PMID- 21009069 TI - New type surgical hand drill. PMID- 21009070 TI - Toxic effects of arsenical compounds as employed in the treatment of diseases in the United States Navy, 1944. PMID- 21009071 TI - Genes and the chemistry of the organism. PMID- 21009073 TI - Education and the National Science Foundation. PMID- 21009072 TI - The physical structure and biological action of nerve cells; with some references to the problems of human flight. PMID- 21009074 TI - The national roster and the Science Foundation. PMID- 21009075 TI - The charter and challenge of UNESCO. PMID- 21009076 TI - Influence of light and temperature on sugar cane and Erianthus. PMID- 21009077 TI - The Argentine curly top of sugar beet. PMID- 21009084 TI - Scientific training. PMID- 21009085 TI - The anemia associated with chronic infection. PMID- 21009086 TI - An observation of the red cell content of the blood of the thoroughbred horse. PMID- 21009087 TI - Fur and feathers; a response to falling temperature. PMID- 21009088 TI - Semi-continuous tap-water aerator. PMID- 21009089 TI - Prozones and blocking effect in normal iso- and hetero-agglutination with cord sera. PMID- 21009090 TI - Research on phenothiazine as an anthelmintic. PMID- 21009091 TI - Early man in Oregon; stratigraphic evidence. PMID- 21009092 TI - Early man in Oregon; pluvial lakes and pumice. PMID- 21009093 TI - Gerontology comes of age. PMID- 21009094 TI - The limitation of creative years. PMID- 21009095 TI - The social significance of Jewish-Christian intermarriage. PMID- 21009096 TI - [Not Available]. PMID- 21009097 TI - [Not Available]. PMID- 21009098 TI - Innervation of the bone marrow. PMID- 21009099 TI - The innervation of the pancreas. PMID- 21009100 TI - Capillaries and mitochondria in neurophil. PMID- 21009101 TI - Neuropathological problems arising from prefrontal leucotomy. PMID- 21009102 TI - Psychopathic personality and crime. PMID- 21009103 TI - Delirious disorientation: the law of the unfamiliar mistaken for the familiar. PMID- 21009104 TI - Neuroses in firemen. PMID- 21009105 TI - Explosive rage following head injury. PMID- 21009107 TI - The psychoneurotic spectrum and dual diagnosis. PMID- 21009106 TI - The impulsive psychopath: a clinical and electrophysiological study. PMID- 21009108 TI - The Kielder experiment. PMID- 21009109 TI - A case of obsessional state of unusual content. PMID- 21009110 TI - Phantasies in evacuated children. PMID- 21009111 TI - Depression in parkinsonism treated by prefrontal leucotomy. PMID- 21009113 TI - Length of treatment in child guidance clinics. PMID- 21009112 TI - Two years' experience of female schizophrenics treated by insulin coma therapy. PMID- 21009114 TI - A syndrome associated with left hand paralysis of central origin. PMID- 21009115 TI - The Starcross reading board; a dynamic aid to reading. PMID- 21009116 TI - Hemiatrophy of the body in adult life. PMID- 21009117 TI - Unusual involvement of the nervous system in generalized lymphoblastoma. PMID- 21009118 TI - Is the epileptic a safe motor vehicle driver?; with some remarks relative to the clinical application of the EEG. PMID- 21009119 TI - Study of a case of pseudo deafmuteness (psychic deafness). PMID- 21009120 TI - The relationship of the vegetative nervous system to angina pectoris (abdominalis). PMID- 21009121 TI - Classification of anxiety reactions (anxiety states). PMID- 21009122 TI - Meniere's syndrome; a comparison of the results of medical and surgical treatment. PMID- 21009123 TI - The clinical diagnosis of central sympathetic disturbances by means of pupillography. PMID- 21009124 TI - Management of the alcoholic by the general practitioner. PMID- 21009125 TI - Mental hospital patients are older. PMID- 21009126 TI - What you, the layman, can do about mental hygiene. PMID- 21009127 TI - [Not Available]. PMID- 21009128 TI - [Not Available]. PMID- 21009129 TI - [Not Available]. PMID- 21009130 TI - [Not Available]. PMID- 21009131 TI - American race relations and the caste system. PMID- 21009132 TI - Dug-out psychiatry. PMID- 21009133 TI - Psychiatric observations in Okinawa Shima. PMID- 21009134 TI - A psychiatric hospital in military government. PMID- 21009135 TI - German words, German personality and Protestantism. PMID- 21009136 TI - Subjective definitions of the Rorschach test situation and their effect on test performance. PMID- 21009137 TI - Personality development of the dinaric warriors. PMID- 21009138 TI - FAMILY life program. PMID- 21009139 TI - Should mother and baby room together? PMID- 21009140 TI - POSTURE fundamentals illustrated; the patient. PMID- 21009141 TI - Tidal drainage of the urinary bladder. PMID- 21009142 TI - Corneal transplantation. PMID- 21009143 TI - Corneal transplantation and nursing care. PMID- 21009144 TI - It's your career, why not plan for it? PMID- 21009145 TI - Nursing care of psychoneurotic patients. PMID- 21009146 TI - Marine hospitals; an opportunity for nurses. PMID- 21009147 TI - Faculty organization. PMID- 21009148 TI - Effect of local anesthetics on cell division and migration following thermal burns of cornea. PMID- 21009149 TI - Standard illuminants in relation to color-testing procedures. PMID- 21009150 TI - Senile hyaline scleral plaques. PMID- 21009151 TI - Traumatic iridodialysis; its surgical correction. PMID- 21009152 TI - Tests for detection and analysis of color blindness; an evaluation of the Ishihara test. PMID- 21009153 TI - Stereoscopic sensitivity in the space eikonometer. PMID- 21009154 TI - Clinical differentiation of emboli in the retinal arteries from endarteritis. PMID- 21009155 TI - An unusual case of Hodgkin's disease; second report. PMID- 21009156 TI - Cardinal points in the static and in the dynamic eye. PMID- 21009158 TI - Ocular changes associated with arachnodactyly. PMID- 21009157 TI - Retinal vascular micrometry and essential hypertension. PMID- 21009159 TI - Traumatic staining of the conjunctiva with indelible lead; report of a case. PMID- 21009160 TI - Discission of the lens in high myopia. PMID- 21009161 TI - The Lempert endaural mastoidectomy and the Lempert fenestration operation for deafness. PMID- 21009162 TI - Inadequacies of functional hearing tests for so-called nerve deafness. PMID- 21009163 TI - Chronic primary glaucoma; diagnostic signs and symptoms, and medical treatment. PMID- 21009164 TI - Preoperative and postoperative treatment at Greens' Eye Hospital. PMID- 21009165 TI - Energy distribution of diffraction gratings as a function of groove form. PMID- 21009166 TI - The paraxial differential transfer coefficients of a lens system. PMID- 21009167 TI - Theory of the space-eikonometer. PMID- 21009168 TI - Modified chromatic value color space. PMID- 21009169 TI - A photoelectric refractometer. PMID- 21009170 TI - Two bilateral spectrograph slits. PMID- 21009171 TI - Spectrographic determination of calcium in microbiological culture media. PMID- 21009172 TI - Plastic surgery in congenital deformities about the face. PMID- 21009173 TI - Pharyngo-esophageal diverticulum. PMID- 21009175 TI - Hearing aids for deaf children. PMID- 21009174 TI - The primary cause of glaucoma. PMID- 21009176 TI - Hearing aid service for children. PMID- 21009177 TI - NEW hearing aid carrier. PMID- 21009178 TI - Paget's disease of the nipple; with special reference to the changes in the ducts. PMID- 21009179 TI - A chronic granulomatous disease of swine with striking resemblance to Hodgkin's disease. PMID- 21009180 TI - Fat embolism. PMID- 21009181 TI - Growth of the rickettsiae of Tsutsugamushi fever on the chorioallantoic membrane of the developing chick embryo. PMID- 21009182 TI - Lesions of skeletal muscles in rheumatoid arthritis; nodular polymyositis. PMID- 21009183 TI - Hydrogen sulfide poisoning; report of two cases, one with fatal outcome, from associated mechanical asphyxia. PMID- 21009184 TI - Hyperplasia of the adrenal cortex associated with bilateral testicular tumors. PMID- 21009185 TI - Studies on ameboid motion and secretion of motor endplates; experimental pathology of the secretory mechanism of motor end-plates in thermal shock. PMID- 21009186 TI - Infectivity of the primary complex of tuberculosis of childhood. PMID- 21009187 TI - Studies on the streptococci (entercococci) of Lancefield group D; recovery of Lancefield group D streptococoi from antemortem and postmortem cultures from infants and young children. PMID- 21009188 TI - Nutrition studies on children living at home; calory intakes on the basis of age from one through ten years. PMID- 21009189 TI - Basal metabolism of eight nursery school children determined at three month intervals. PMID- 21009190 TI - Pyopneumothorax in a premature baby successfully treated with penicillin. PMID- 21009191 TI - Histoplasmosis in children; review of the literature, with report of a case. PMID- 21009192 TI - Mortality trends in the newborn. PMID- 21009193 TI - Cold agglutinins as a cause of hemolysis in erythroblatosis neonatorum. PMID- 21009194 TI - Congenital intestinal obstruction in the newborn; report of three cases with successful results of surgical treatment. PMID- 21009195 TI - Congenital morphinism; report of a case. PMID- 21009197 TI - Tuberculosis of bone. PMID- 21009196 TI - Recurrent or suppurative parotitis. PMID- 21009199 TI - [Not Available]. PMID- 21009198 TI - Some aspects of infantile pathology in the cities of the Western Netherlands during the time of the blockade. PMID- 21009200 TI - [Not Available]. PMID- 21009201 TI - [Not Available]. PMID- 21009202 TI - [Not Available]. PMID- 21009203 TI - [Not Available]. PMID- 21009204 TI - [Not Available]. PMID- 21009205 TI - [Not Available]. PMID- 21009206 TI - [Not Available]. PMID- 21009207 TI - [Not Available]. PMID- 21009208 TI - [Not Available]. PMID- 21009209 TI - [Not Available]. PMID- 21009210 TI - [Not Available]. PMID- 21009211 TI - The erythrocyte sedimentation rate and its applications to pediatrics. PMID- 21009212 TI - Psychometrics in pediatrics. PMID- 21009213 TI - Splenic neutropenia. PMID- 21009214 TI - Hirschsprung's disease. PMID- 21009215 TI - Lymphoblastoma? PMID- 21009216 TI - Tuberculosis in children. PMID- 21009217 TI - Shall we tuberculin test school children? PMID- 21009218 TI - Striving for completeness in a school health program. PMID- 21009219 TI - School health education. PMID- 21009220 TI - [Not Available]. PMID- 21009221 TI - [Not Available]. PMID- 21009222 TI - [Not Available]. PMID- 21009224 TI - [Not Available]. PMID- 21009223 TI - [Not Available]. PMID- 21009225 TI - [Not Available]. PMID- 21009226 TI - DESOXYEPHEDRINE; its chemistry and uses. PMID- 21009227 TI - Hydrophilic ointment. PMID- 21009228 TI - THERAPEUTIC use of curare. PMID- 21009230 TI - Dispensing in State institutions. PMID- 21009229 TI - What about our pharmacy boards? PMID- 21009231 TI - ACETANILID powder, compound. PMID- 21009232 TI - ALUMINUM acetate solution. PMID- 21009233 TI - BEEF extract. PMID- 21009234 TI - CALCIUM GLYCEROPHOSPHATE. PMID- 21009235 TI - FERRIC glycerophosphate. PMID- 21009236 TI - IODINE ointment. PMID- 21009237 TI - [Not Available]. PMID- 21009238 TI - [Not Available]. PMID- 21009241 TI - Dust in the home and factory. PMID- 21009239 TI - Penicillin preparations. PMID- 21009240 TI - A penicillin distributing centre in operation. PMID- 21009242 TI - Shingles. PMID- 21009243 TI - A note on abrasions and other minor injuries. PMID- 21009244 TI - What is the N.A.P.T.? PMID- 21009246 TI - MENOPAUSE. PMID- 21009245 TI - ORAL administration of penicillin. PMID- 21009247 TI - The influence of sodium lauryl sulfate on the biologic response to the gonadotropins and to insulin. PMID- 21009249 TI - Respiratory flow in Mustelus. PMID- 21009248 TI - Vitamin deficiency and overdosage and the resistance of rats to lowered barometric pressures. PMID- 21009250 TI - The number and relative concentrations of protein constituents of canine pancreatic juice as determined by electrophoresis. PMID- 21009251 TI - The action of acetylcholine and epinephrine on the turtle ventricle. PMID- 21009252 TI - The effect of sodium and chloride salts in preventing the shocklike state following venous occlusion of a limb in the dog. PMID- 21009253 TI - Changes in the blood during chronic and acute dehydration. PMID- 21009254 TI - The effect of protein and fat content of the diet upon the toxicity of benzene for rats. PMID- 21009255 TI - The increased susceptibility of protein-deficient dogs to benzene poisoning. PMID- 21009256 TI - The effect of acetylcholine on the atropinized, denervated heart. PMID- 21009257 TI - Consideration of the mechanism of neutralization of endogenous gonadotrophic hormone of the rat by antigonadotrophic serum. PMID- 21009258 TI - Alterations in the properties of dog hepatic bile with increasing age of the chronic biliary fistula. PMID- 21009259 TI - Age, sex, carbohydrate, adrenal cortex and other factors in anoxia. PMID- 21009260 TI - The survival of non-adrenalectomized rats in burn shock with and without adrenal cortical hormone treatment. PMID- 21009261 TI - The changes in components A and B of prothrombin in the dog following hepatectomy. PMID- 21009262 TI - The effect of exposure to oxygen at high pressure upon the tonus and respiration of pyloric muscle from the rabbit. PMID- 21009263 TI - Effect of ambient air temperature and of hand temperature on blood flow in hands. PMID- 21009264 TI - The effects of intracisternal injection of potassium phosphate on the rate and rhythm of the heart and on the blood pressure and on the respiration of the dog. PMID- 21009265 TI - The fate of CO in the body during recovery from mild carbon monoxide poisoning in man. PMID- 21009266 TI - The elimination of carbon monoxide from the human body with reference to the possible conversion of CO to CO2. PMID- 21009268 TI - Developments in human adjustment and rehabilitation. PMID- 21009267 TI - The role of the proprioceptors in shivering. PMID- 21009269 TI - Some relationships between children's symptoms of maladjustment and background factors. PMID- 21009270 TI - Diagnostic patterns on the Minnesota multiphasic personality inventory. PMID- 21009271 TI - The discriminatory value of a test pattern in the high grade familial defective. PMID- 21009272 TI - Psychotherpay in a case of obesity. PMID- 21009273 TI - The dynamics of non-directive psychotherapy. PMID- 21009274 TI - Directive psychotherapy; the technique of psychological palliation. PMID- 21009276 TI - Therapeutic aspects of the psychological interview. PMID- 21009275 TI - A quick method of analyzing the similarity of profiles. PMID- 21009277 TI - Clinical values of projective techniques in an Army hospital. PMID- 21009278 TI - Blood and blood derivatives; a new public health field. PMID- 21009279 TI - Typhoid vaccine studies; the suitability of Vi antigen as an auxiliary immunogen for typhoid vaccine; progress report. PMID- 21009280 TI - Age and sex variations in the prevalence and onset of diabetes mellitus. PMID- 21009281 TI - Out break of typhoid fever with orange juice as the vehicle, illustrating the value of immunization. PMID- 21009282 TI - Epidemiological studies on infectious hepatitis. PMID- 21009283 TI - PROPOSED report on the educational qualifications of nutritionists in health agencies. PMID- 21009284 TI - Occurrence of Shigella types in the military population of the southeastern United States, 1943 and 1944. PMID- 21009285 TI - Incidence of certain biological characteristics among food poisoning staphylococci. PMID- 21009286 TI - A new statement of school health policies. PMID- 21009287 TI - Full-time health services in Nova Scotia. PMID- 21009288 TI - Findings on re-Schick testing of Air Force personnel. PMID- 21009289 TI - Salmonellosis; a public health problem. PMID- 21009291 TI - Mapping our new frontiers of health. PMID- 21009290 TI - Food poisoning due to Salmonella newport. PMID- 21009292 TI - Educating food handlers. PMID- 21009293 TI - The moral and social factors in venereal-disease control. PMID- 21009294 TI - A method for the rapid production of citrinin. PMID- 21009295 TI - [Not Available]. PMID- 21009296 TI - [Not Available]. PMID- 21009298 TI - [Not Available]. PMID- 21009297 TI - [Not Available]. PMID- 21009299 TI - [Not Available]. PMID- 21009300 TI - [Not Available]. PMID- 21009301 TI - [Not Available]. PMID- 21009302 TI - [Not Available]. PMID- 21009304 TI - [Not Available]. PMID- 21009303 TI - [Not Available]. PMID- 21009306 TI - [Not Available]. PMID- 21009305 TI - [Not Available]. PMID- 21009307 TI - [Not Available]. PMID- 21009308 TI - [Not Available]. PMID- 21009309 TI - [Not Available]. PMID- 21009310 TI - [Not Available]. PMID- 21009311 TI - [Not Available]. PMID- 21009312 TI - Drug control. PMID- 21009313 TI - Dental health advisers in public health work. PMID- 21009315 TI - The medical profession and the schools. PMID- 21009314 TI - The new Division of Adult Hygiene and Geriatrics. PMID- 21009316 TI - The effect of fluorescent light on vision. PMID- 21009317 TI - A cycle of morphine addiction; biological and psychological studies. PMID- 21009318 TI - A cycle of morphine addiction; biological and psychological studies. PMID- 21009319 TI - The release of antigen from certain bacteria on treatment with ether. PMID- 21009320 TI - Sanitary laws in relation to public health. PMID- 21009321 TI - INFANT mortality declined to a record low during the war. PMID- 21009322 TI - [Not Available]. PMID- 21009323 TI - [Not Available]. PMID- 21009324 TI - The anatomy of the blood vessels of the human lung as applied to chest radiology. PMID- 21009325 TI - Energy absorption in radium therapy. PMID- 21009326 TI - Recent advances in investigation of the small intestine. PMID- 21009327 TI - A feed-back amplifier for ionisation currents. PMID- 21009329 TI - A review of recent French literature on radiotherapy. PMID- 21009328 TI - External and internal thorium-x therapy. PMID- 21009330 TI - The effect of x-rays on Leishmania tropica in vitro. PMID- 21009331 TI - Eighth Stanley Melville memorial lecture; series and parallel. PMID- 21009333 TI - The x-ray department and the radiographer. PMID- 21009332 TI - X-ray set failure and the petrol electric generator. PMID- 21009334 TI - Delayed internal fixation of compound battle fractures in the Mediterranean theater of operations. PMID- 21009335 TI - The incidence of complications in the use of transfixion pins and wires for skeletal traction. PMID- 21009336 TI - Abdominal surgery in an evacuation hospital. PMID- 21009337 TI - Chemotherapy in traumatic surgery of the abdomen. PMID- 21009338 TI - Lung abscess complicating penetrating wounds of the chest. PMID- 21009339 TI - The operative treatment of decubitus ulcer. PMID- 21009340 TI - The role of chemotherapy in wounds and surgical infections; clinical and bacteriologic studies. PMID- 21009341 TI - Pain in men wounded in battle. PMID- 21009342 TI - Retroperitoneal (mesenteric pouch) hernia. PMID- 21009343 TI - Cystic disease of the liver. PMID- 21009344 TI - Congenital cystic dilatation of the common bile duct. PMID- 21009345 TI - Traumatic rupture of the gall-bladder. PMID- 21009346 TI - Sarcoma complicating Paget's disease of bone. PMID- 21009347 TI - Extradural spinal hemorrhage. PMID- 21009348 TI - Pharyngeal diverticula. PMID- 21009349 TI - Acrylic resin for the closure of skull defects. PMID- 21009350 TI - The surgical treatment of traumatic aneurysms. PMID- 21009351 TI - Some observations on carcinoma of the prostate treated with oestrogens, as demonstrated by serial biopsies. PMID- 21009352 TI - A histological study of a predegenerated nerve autograft. PMID- 21009353 TI - Obstructive diaphragmatic hernia resulting from old gunshot wound of the chest; a report of three cases. PMID- 21009354 TI - Pelvic ectopic kidney. PMID- 21009355 TI - Torsion of the great omentum; report of four cases. PMID- 21009356 TI - Physiological gastrectomy. PMID- 21009357 TI - Thoraco-abdominal wounds in war. PMID- 21009358 TI - Principles in early reconstructive surgery of severe thermal burns of the hands. PMID- 21009359 TI - An aid in the post-operative management of temporary ileal fistula after the Lahey right hemicolectomy. PMID- 21009360 TI - Experiences with transthoracic oesophagectomy and gastrectomy. PMID- 21009361 TI - Penicillin treatment of acute haematogenous osteomyelitis. PMID- 21009362 TI - The status of hormonal bio-assay in malignant disease of the testicle. PMID- 21009363 TI - Chronic hypertrophic ileocaecal tuberculosis, and its relation to regional ileitis (Crohn's disease). PMID- 21009364 TI - Intussusception of the sigmoid due to simple polypus with annular carcinoma of the descending colon. PMID- 21009365 TI - Hernia traversing the lesser sac. PMID- 21009366 TI - Carcinoma of the small intestines. PMID- 21009367 TI - Hernia of the ileum through a hole in the transverse mesocolon. PMID- 21009368 TI - An enormous epithelioma adenoides cysticum of the scalp. PMID- 21009369 TI - Sarcoma of the metatarsal bones. PMID- 21009371 TI - A large testicular tumour. PMID- 21009370 TI - A case of common iliac aneurysm in a child. PMID- 21009372 TI - A fibrolipoma of the cheek. PMID- 21009373 TI - [Not Available]. PMID- 21009374 TI - [Not Available]. PMID- 21009375 TI - [Not Available]. PMID- 21009376 TI - [Not Available]. PMID- 21009377 TI - [Not Available]. PMID- 21009378 TI - [Not Available]. PMID- 21009379 TI - [Not Available]. PMID- 21009380 TI - [Not Available]. PMID- 21009381 TI - [Not Available]. PMID- 21009382 TI - [Not Available]. PMID- 21009384 TI - Nonmalignant tumors of the uterine corpus. PMID- 21009383 TI - Diagnosis and management of uterine carcinoma and sarcoma. PMID- 21009385 TI - Merits and a technic for complete hysterectomy. PMID- 21009386 TI - Nonmalignant diseases of the cervix. PMID- 21009387 TI - Indications and contraindications in the irradiation therapy of benign uterine conditions. PMID- 21009388 TI - Backache in women and uterine retrodisplacement. PMID- 21009389 TI - The treatment of habitual abortion with estrogen and progesterone. PMID- 21009390 TI - Uterosalpingography. PMID- 21009391 TI - Operations for sterility. PMID- 21009393 TI - Continuous spinal and continuous caudal analgesia in cesarean section. PMID- 21009392 TI - The control of pain and fear in the management of labor and delivery. PMID- 21009394 TI - Roentgenological visualization of the sacral hiatus during late pregnancy. PMID- 21009395 TI - The roentgenological visualization of the placenta. PMID- 21009396 TI - Hemorrhage of pregnancy. PMID- 21009397 TI - Ruptured uterus in the last trimester of pregnancy; a report of 105 cases. PMID- 21009398 TI - Uterine contractions during pregnancy and labor observed with the tocograph. PMID- 21009399 TI - Forceps for delivery; their use and abuse. PMID- 21009400 TI - The Waters operation in modern obstetrics. PMID- 21009401 TI - External version. PMID- 21009402 TI - Blood, blood derivatives and blood substitutes in obstetric and gynecologic practice. PMID- 21009403 TI - Immediate care of the newborn. PMID- 21009404 TI - Physical medicine in the Army; its effect on civil practice. PMID- 21009405 TI - Minor industrial injuries; early recognition, prevention, notification and treatment. PMID- 21009406 TI - The management of rheumatoid arthritis. PMID- 21009407 TI - Social aspect of physical and industrial medicine. PMID- 21009408 TI - Hydrological treatment of liver and gall-bladder disorders. PMID- 21009409 TI - [Not Available]. PMID- 21009410 TI - [Not Available]. PMID- 21009411 TI - [Not Available]. PMID- 21009412 TI - [Not Available]. PMID- 21009413 TI - [Not Available]. PMID- 21009414 TI - [Not Available]. PMID- 21009415 TI - Report of case of acute hemorrhagic adrenalitis. PMID- 21009416 TI - The relief of renal colic and renal suppression; a preliminary report. PMID- 21009417 TI - A pyelographic sign in the diagnosis of perinephric abscess. PMID- 21009418 TI - Renal adenomas in hypernephromatous kidneys; a study of their incidence, nature and relationship. PMID- 21009419 TI - Liposarcoma of kidney; report of a case presenting an unusual syndrome. PMID- 21009420 TI - Mucinous adenocarcinoma of the pelvis of the kidney. PMID- 21009421 TI - Ureteropelvic obstructions in children; incidence and etiology. PMID- 21009422 TI - Circumcaval ureter; report of a case with a consideration of the preoperative diagnosis and successful plastic repair. PMID- 21009423 TI - Unusual ureteral anomalies; case reports. PMID- 21009424 TI - Congenital diverticulum of the female urethra. PMID- 21009425 TI - A study of the effect of stilbestrol therapy on the size of the benignly hypertrophied prostate gland. PMID- 21009426 TI - The importance of routine cystoscopy in prostatism. PMID- 21009427 TI - Osteitis pubis. PMID- 21009428 TI - An instrument for transurethral anesthesia. PMID- 21009429 TI - Urogenital complications of dengue fever. PMID- 21009430 TI - War injuries of the urinary tract. PMID- 21009431 TI - Urogenital wounds in an evacuation hospital. PMID- 21009432 TI - Evaluating potentialities of human spermatozoa. PMID- 21009433 TI - Penicillin in propylene glycol; a preliminary report. PMID- 21009434 TI - WAR against prostitution must go on; a report on the current status of commercialized prostitution. PMID- 21009435 TI - Our strength is in united action; a report on progress in social protection in the States and communities with suggestions for more effective cooperation among agencies concerned. PMID- 21009436 TI - The venereal disease heritage of World War II; a Navy view of demobilization and postwar venereal disease and social hygiene problems. PMID- 21009437 TI - Current Army venereal disease rates. PMID- 21009438 TI - The Army venereal disease education program for demobilization. PMID- 21009440 TI - Education for case-finding. PMID- 21009439 TI - The postwar syphilis control problem in the United States. PMID- 21009441 TI - The synergistic action of penicillin and mapharsen (oxophenarsine hydrochloride) in the treatment of experimental syphilis. PMID- 21009442 TI - San Francisco industrial venereal disease educational and case-finding program. PMID- 21009443 TI - Regarding the unusual effect of penicillin therapy upon the uterus. PMID- 21009444 TI - Lead poisoning of cattle. PMID- 21009445 TI - Studies of vesicular stomatitis with special reference to a virus of swine origin. PMID- 21009446 TI - An outbreak of salmonellosis in horses and mules. PMID- 21009447 TI - INSPECTION OF Human food. PMID- 21009448 TI - Experimental edema and ascites in poults. PMID- 21009449 TI - The incidence of intestinal protozoa in the dog. PMID- 21009450 TI - Rabies in cattle. PMID- 21009452 TI - Skin grafting in a cat. PMID- 21009451 TI - Abortion in sheep following the administration of phenothiazine. PMID- 21009453 TI - A precocious heifer; cesarean section. PMID- 21009454 TI - PULLORUM disease; historical sketch. PMID- 21009455 TI - POULTRY medicine. PMID- 21009456 TI - Tick infestation as an aetiological factor in diseases of unknown origin among cattle. PMID- 21009457 TI - Modern therapeutics; a review of the use of sulphonamides and of penicillin and other antibiotics from bacteria and moulds as therapeutic agents. PMID- 21009458 TI - A note on the efficacy of commercial anti-anthrax bacterins. PMID- 21009459 TI - The excretion of tortoise shells by cattle. PMID- 21009460 TI - The lung worm, Filaroides osleri (Cobbold) in South African bred dogs; preliminary note. PMID- 21009461 TI - The lung worm, Filaroides osleri (Cobbold) in dogs; a clinical report. PMID- 21009462 TI - Milk fever in a ewe. PMID- 21009463 TI - The relation of immunity in rabies to the antibody content of the serum. PMID- 21009464 TI - Lymphatic leukemia with a myeloid blood picture complicated by a severe microcytic hypochromic anemia in a dog. PMID- 21009465 TI - The adrenal bodies. PMID- 21009466 TI - The veterinarian and the poultry industry. PMID- 21009467 TI - Fowl coccidiosis. PMID- 21009468 TI - Trichinosis. PMID- 21009469 TI - Neurogenic sarcoma in a dog. PMID- 21009470 TI - Complete foreign body obstruction of the duodenum. PMID- 21009471 TI - Infectious equine encephalomyelitis in the United States in 1944. PMID- 21009472 TI - About practice; an effective treatment for foot rot. PMID- 21009473 TI - Bovine mastitis caused by a Corynebacterium not previously described. PMID- 21009474 TI - Bovine obstetrical work. PMID- 21009475 TI - Some newer chemotherapeutic agents. PMID- 21009477 TI - Unusual causes of death among dogs. PMID- 21009476 TI - Penicillin in veterinary medicine. PMID- 21009478 TI - Trials with sodium fluoride as an ascaricide for swine. PMID- 21009480 TI - Impacted sinuses in a cow. PMID- 21009479 TI - Infectious pododermatitis in dairy cattle. PMID- 21009481 TI - Tick paralysis in beef cattle due to Dermacentor andersoni. PMID- 21009482 TI - The brown dog tick, with special reference to its control and eradication. PMID- 21009483 TI - Difficult fracture reduction with the aid of the Stader splint. PMID- 21009484 TI - Report of Special Committee on Canine Filariasis, Illinois State Veterinary Medical Association. PMID- 21009485 TI - Convulsions in dogs. PMID- 21009487 TI - [Not Available]. PMID- 21009486 TI - [Not Available]. PMID- 21009489 TI - [Not Available]. PMID- 21009488 TI - [Not Available]. PMID- 21009490 TI - [Not Available]. PMID- 21009491 TI - [Not Available]. PMID- 21009492 TI - An infectious enteritis of young turkeys associated with Cochlosoma sp. PMID- 21009493 TI - Active immunisation as against passive segregation with reference to tuberculosis. PMID- 21009494 TI - Reflections on the planning of small animal hospitals. PMID- 21009495 TI - Construction and architecture of a small animal clinic. PMID- 21009496 TI - Essentials of a hospital for small animals. PMID- 21009497 TI - The modern animal hospital. PMID- 21009498 TI - The veterinarian of World War II. PMID- 21009499 TI - Reflections on the value of tartar emetic for the treatment of trypanosomiases. PMID- 21009500 TI - Veterinary education; the essentials of a modern vocational training and the proper rule of the universities in advancing specialised veterinary knowledge; a suggested programme. PMID- 21009501 TI - Oestrogenic induction of lactation in cattle. PMID- 21009502 TI - HUNDRED years, 1844-1944. PMID- 21009503 TI - SHORT history of the veterinary art in antiquity. PMID- 21009504 TI - SHORT account of the circumstances which led to the petition for and the grant in 1844 of the charter of incorporation of the Royal College of Veterinary Surgeons. PMID- 21009506 TI - ROYAL (DICK) Veterinary College, Edinburgh. PMID- 21009505 TI - BRITISH veterinary colleges; the Royal Veterinary College and Hospital, London. PMID- 21009507 TI - GLASGOW Veterinary College. PMID- 21009508 TI - PUBLIC veterinary services in Great Britain and Ireland. PMID- 21009509 TI - MEAT inspection in England and Wales and in Scotland. PMID- 21009511 TI - VETERINARY development in Canada. PMID- 21009510 TI - MILK in (a) England and Wales and (b) in Scotland. PMID- 21009512 TI - VETERINARY profession in South Africa. PMID- 21009513 TI - DEVELOPMENT and achievements of the British India Civil Veterinary Services. PMID- 21009514 TI - GENERAL, or private, veterinary practice. PMID- 21009515 TI - SOME special aspects of veterinary practice. PMID- 21009516 TI - BRITISH veterinary periodicals. PMID- 21009517 TI - Studies on virus diseases of fish; lymphocystis disease in Centrarchidae. PMID- 21009518 TI - The innervation of the flexor digitorum profundus and lumbrical muscles. PMID- 21009519 TI - Hyperplastic changes in the nervous system of a frog (Rana) as associated with multiple functional limbs. PMID- 21009520 TI - A criterion of luteal activity in the mouse. PMID- 21009521 TI - The extrusive growth and attrition of the incisors in Cynomys L. ludovicianus (Ord.). PMID- 21009522 TI - The distribution of alkaline phosphatase in the cyclic growth of the rat hair follicle. PMID- 21009523 TI - The effect of colchicine on early cleavage of mouse ova. PMID- 21009524 TI - The postnatal development of the oviduct of the rat. PMID- 21009525 TI - The localization of phosphatases in the Golgi region of intestinal and other epithelial cells. PMID- 21009526 TI - The study of nephridia and genital ducts since 1895. PMID- 21009527 TI - Further notes on tobacco in New Guinea. PMID- 21009528 TI - Notes on Cheyenne child life. PMID- 21009529 TI - Kroeber's Configurations of culture growth. PMID- 21009530 TI - [Not Available]. PMID- 21009531 TI - [Not Available]. PMID- 21009532 TI - [Not Available]. PMID- 21009533 TI - [Not Available]. PMID- 21009534 TI - [Not Available]. PMID- 21009535 TI - On the cerebral motor cortex of the ant-eater (Tamandua tetradactyla L.) preliminary report. PMID- 21009536 TI - [Not Available]. PMID- 21009537 TI - [Not Available]. PMID- 21009538 TI - [Not Available]. PMID- 21009539 TI - [Not Available]. PMID- 21009540 TI - [Not Available]. PMID- 21009541 TI - [Not Available]. PMID- 21009542 TI - [Not Available]. PMID- 21009543 TI - [Not Available]. PMID- 21009544 TI - [Not Available]. PMID- 21009545 TI - [Not Available]. PMID- 21009546 TI - [Not Available]. PMID- 21009547 TI - [Not Available]. PMID- 21009548 TI - [Not Available]. PMID- 21009549 TI - The isolation of estrone sulfate from the urine of stallions. PMID- 21009550 TI - [Not Available]. PMID- 21009551 TI - Studies in species adaptation; continuous exposure of paramecia to methylcholanthrene and other agents for more than five years. PMID- 21009552 TI - Studies in species adaptation; continuous and discontinuous exposure of a flat worm to methylcholanthrene and to phenanthrene. PMID- 21009553 TI - Methylcholanthrene and the environment of Paramecium. PMID- 21009554 TI - Organ changes in rats exposed repeatedly to lowered oxygen tension with reduced barometric pressure. PMID- 21009555 TI - Effect of adrenalectomy and ovariectomy on mammary carcinogenesis in strain C3H mice. PMID- 21009556 TI - Quantitative relation between the number of organized centers and tissue volume in regenerating masses of minced body sections of Hydra. PMID- 21009557 TI - [Not Available]. PMID- 21009558 TI - [Not Available]. PMID- 21009560 TI - [Not Available]. PMID- 21009559 TI - [Not Available]. PMID- 21009561 TI - The use of infra-red spectra for analysis. PMID- 21009562 TI - A dynamic method for observing the antimony chloride reaction with vitamin A and related substances. PMID- 21009563 TI - The estimation of sucrose in sugar-dried egg by polarimetric methods. PMID- 21009564 TI - A colorimetric method for the determination of uranium in leach liquors. PMID- 21009565 TI - Rapid colorimetric estimation of iodine in kelp. PMID- 21009566 TI - The effects of p-aminobenzoic acid, pantothenic acid and pyridoxin upon respiration of Neurospora. PMID- 21009567 TI - Sulfanilamide and respiration of Neurospora. PMID- 21009568 TI - The photochemical production of oxygen and hydrogen ion by isolated chloroplasts. PMID- 21009569 TI - The urinary excretion of trigonelline- and nicotinic acid-like substances in human subjects after the ingestion of trigonelline and after smoking. PMID- 21009570 TI - Studies on the biochemistry of Tetrahymena; folic acid as a growth factor for T. geleii W. PMID- 21009571 TI - Reagents for the detection of hydrogen peroxide production by bacteria in plate cultures (with notes for the preparation of 2,7-diaminofluorene dihydrochloride). PMID- 21009572 TI - The fermentation of lactose by an extract of streptococcus thermophilus. PMID- 21009573 TI - Succinic dehydrogenase activity of certain endocrine tissues of the rat. PMID- 21009574 TI - Thermal destruction of influenza A virus hemagglutinin; the effect of pH. PMID- 21009575 TI - Dispensability of dietary niacin for reproduction and lactation in the rat. PMID- 21009577 TI - The Kiliani reaction as a direct measure of reducing groups. PMID- 21009576 TI - Note on the orcinol reagent. PMID- 21009578 TI - The production of riboflavin by Ashbya gossypii. PMID- 21009579 TI - Further studies on the metabolism of nicotinic acid and related compounds in the horse. PMID- 21009580 TI - Note on the poison produced by the Polydesmus (Fontaria) vicinus, Lin. PMID- 21009581 TI - The application of the law of mass action to binding by proteins; interactions with calcium. PMID- 21009582 TI - Electrophoretic analysis of swine plasma and serum. PMID- 21009583 TI - Failure to demonstrate transmethylation of homocystine by a strain of E. coli requiring methionine for growth. PMID- 21009584 TI - The antibacterial activity of simple derivatives of 2-aminophenol. PMID- 21009587 TI - Properties of catalysis of coupled oxidation of alcohols. PMID- 21009590 TI - The production of penicillin using fractions obtained from aqueous extracts of pea (Pisum sativum). PMID- 21009594 TI - Biochemical characterization of actions of chemotherapeutic agents: lack of gross displacement of pantothenate and p-aminobenzoate from micro-organisms, by pantoyltaurine and sulphanilamide. PMID- 21009595 TI - Isolation from liver of new factors essential for the growth of Lactobacillus helveticus and Streptococcus lactis R. PMID- 21009596 TI - Anaemia of nutritional origin in the rat. PMID- 21009603 TI - Polarimetric determination of starch in cereal products; critical studies of methods for the determination of starch in whole wheat, granular, and patent flours. PMID- 21009604 TI - A comparison of five methods for determining starch content of wheat. PMID- 21009605 TI - Equilibrium diagrams for binary mixtures of aniline, ethylaniline, and diethylaniline. PMID- 21009606 TI - Determination of fluorides in water by means of a photoelectric colorimeter. PMID- 21009607 TI - Dissimilation of glucose by Bacillus subtilis (Ford's strain). PMID- 21009609 TI - The ether-soluble extractive of black sprucewood. PMID- 21009608 TI - Catalytic dehydrogenation of primary and secondary alcohols with copper-chromium oxide. PMID- 21009610 TI - A note on the hydrogenation of beta-phenyl-alpha oximinopropionic acid. PMID- 21009611 TI - Oxidation of 3,4-dimethoxycinnamic acid and substitution products with alkaline potassium permanganate solution. PMID- 21009612 TI - The synthesis of 7-methoxy-l-isoquinolone. PMID- 21009613 TI - Phenylation of some hydrocarbons with a phenyl halide activated by an alkali amide. PMID- 21009614 TI - 6'-methoxyrubanol-9. PMID- 21009615 TI - Contributions to the study of marine products; spongosterol. PMID- 21009616 TI - Contributions to the study of marine products; microcionasterol and other sterols of sponges. PMID- 21009617 TI - Contributions to the study of marine products; chalinasterol. PMID- 21009618 TI - Acyl interconversions of aryl polyacylglycosides. PMID- 21009619 TI - On stomatitis ulcerosa; etiology and therapeutics. PMID- 21009620 TI - Decrease in the incidence of dental caries in 6-7 years old Copenhagen elementary school children 1936-1943. PMID- 21009621 TI - The combination bread-sugar as a cause for dental caries. PMID- 21009623 TI - The Brantford fluorine experiment. PMID- 21009622 TI - Mandibular movements and the arrangement of teeth. PMID- 21009624 TI - [Not Available]. PMID- 21009625 TI - [Not Available]. PMID- 21009626 TI - [Not Available]. PMID- 21009627 TI - Study of congenitally missing second premolars and space factors in the arches. PMID- 21009628 TI - Electron microscope study of the mechanism of fluorine deposition in teeth. PMID- 21009630 TI - Observations on induced caries in rats; effects of excessive sugar in the diet. PMID- 21009629 TI - The effect of sodium fluoride on the solubility of calcium phosphate, tooth enamel and whole teeth in lactic acid. PMID- 21009631 TI - Studies on the oxidation-reduction potentials of saliva. PMID- 21009632 TI - Evaluation of antimicrobial agents; the germicidal activity of a synthetic detergent, DC-12. PMID- 21009633 TI - Status of fluoride therapy in dentistry. PMID- 21009634 TI - Systemic introduction of sodium iodide into calcified dental tissues. PMID- 21009635 TI - The histological demonstration of phosphatase in the development of the enamel organ. PMID- 21009637 TI - Graduate training in oral surgery. PMID- 21009638 TI - Control of bone fragments in maxillofacial surgery. PMID- 21009636 TI - Evolution of orthodontic theory and practice. PMID- 21009639 TI - Study of one hundred fifty cases of fracture of the upper jaw in an overseas maxillofacial center. PMID- 21009640 TI - Correction of abnormal mandibular protrusion by intra-oral operation. PMID- 21009641 TI - Avoidance of severe anoxia in nitrous oxide anesthesia. PMID- 21009642 TI - Unerupted supernumerary mandibular bicuspids; report of case. PMID- 21009643 TI - Observations on the definitive treatment of maxillofacial injuries. PMID- 21009644 TI - Treatment of gunshot fractures of the mandible. PMID- 21009645 TI - Acetylsalicylic acid (aspirin) as a cause of bleeding. PMID- 21009646 TI - Papillary cystadenoma lymphomatosum (adenolymphoma) of the parotid region; report of case. PMID- 21009647 TI - Penicillin in submandibular cellulitis and clinical septicemia; report of case. PMID- 21009648 TI - Making dentistry a reading profession. PMID- 21009649 TI - Discoloration of acrylic resins for tooth restorations. PMID- 21009650 TI - A clinical investigation of some hemostatic agents applied to different lesions of the mouth. PMID- 21009651 TI - Prothesenhygiene. PMID- 21009652 TI - [Not Available]. PMID- 21009653 TI - [Not Available]. PMID- 21009654 TI - [Not Available]. PMID- 21009655 TI - [Not Available]. PMID- 21009656 TI - [Not Available]. PMID- 21009657 TI - Carbohydrate metabolism and the skin. PMID- 21009658 TI - Epidermolysis bullosa; a suggestion as to possible causation. PMID- 21009660 TI - Effect of endocrine substances on the adult human scalp. PMID- 21009661 TI - Epidermodysplasia hystricoidis bullosa; report of a case with histopathologic study. PMID- 21009659 TI - Acne vulgaris occurring in the tropics in a pigmentary and pilosebaceous nevus. PMID- 21009662 TI - Dermatology in an Army station hospital serving in Italy. PMID- 21009664 TI - Treatment of dermatoses with vasodilators. PMID- 21009663 TI - Fixed bullous eruption due to sulfathiazole. PMID- 21009665 TI - Pigmentation of hair on transplanted skin in hooded rats. PMID- 21009666 TI - Lichen sclerosus et atrophicus in childhood. PMID- 21009667 TI - Differentiation of lepromatous from neural leprosy; the basis, a method, and report of five cases. PMID- 21009668 TI - Sandals, and hygiene and infections of the feet. PMID- 21009669 TI - The adrenal glands in pemphigus vulgaris; report of six autopsies and review of the literature. PMID- 21009670 TI - Cutaneous and subcutaneous lesions of the lower limbs in connection with the veins; differential diagnosis. PMID- 21009671 TI - Dermatitis venenata following use of penicillin ointment. PMID- 21009672 TI - New cutaneous bactericidal agent used in soap; further practical studies. PMID- 21009673 TI - Dermatitis medicamentosa associated with secondary polycythemia; report of a case. PMID- 21009674 TI - Waterhouse-Friderichsen syndrome; report of a case. PMID- 21009675 TI - Colloidoclastic shock following injection of oxophenarsine hydrochloride (mapharsen). PMID- 21009676 TI - Carbarsone in the treatment of pemphigus; a preliminary report. PMID- 21009677 TI - Fever and sterile abscess formation accompanying treatment of syphilis with penicillin. PMID- 21009678 TI - Erysipeloid treated successfully with injections of penicillin report of a case. PMID- 21009679 TI - Demonstration of effect of nutrition on the skin. PMID- 21009680 TI - Bowen's disease of penis; late latent syphilis (treated). PMID- 21009681 TI - A case for diagnosis (sarcoid; late cutaneous syphilid?). PMID- 21009682 TI - Postsyphilitic dyschromia; late dyschromic pinta? (treated). PMID- 21009683 TI - Pyoderma gangrenosum associated with nonspecific ulcerative colitis. PMID- 21009684 TI - A case for diagnosis (lupus vulgaris erythematosus of Leloir?). PMID- 21009685 TI - Dystrophia mediana canaliformis. PMID- 21009686 TI - Trichophytosis barbae. PMID- 21009687 TI - Scleroderma en coup de sabre. PMID- 21009688 TI - Systematized epithelial nevus. PMID- 21009689 TI - Adenoma sebaceum (Pringle type forme fruste). PMID- 21009690 TI - Herpes simplex resembling herpes zoster. PMID- 21009691 TI - Recurrent urticaria chronica. PMID- 21009692 TI - A case for diagnosis (allergic eruption?). PMID- 21009693 TI - Alopecia prematura. PMID- 21009695 TI - Common ailments of quality in processed foods. PMID- 21009694 TI - Sarcoid. PMID- 21009696 TI - Lecithin increases the effect of shortening in bread. PMID- 21009697 TI - Control of microbiological food spoilage by fumigation with epoxides. PMID- 21009698 TI - What sanitation means to the processor. PMID- 21009699 TI - How meat is dehydrated in New Zealand. PMID- 21009700 TI - Oil of angelica; production and characteristics. PMID- 21009701 TI - The need for reform in statutes affecting illegitimacy. PMID- 21009702 TI - Medico-legal examinations and reports. PMID- 21009703 TI - THE McNAGHTEN Rules and the irresistible impulse defence. PMID- 21009704 TI - A study in gene action using different dosages and alleles of vestigial in Drosophila melanogaster. PMID- 21009705 TI - On lethal mutations in natural populations. PMID- 21009706 TI - Isolation by distance under diverse systems of mating. PMID- 21009707 TI - Cytological studies in Culex; somatic reduction divisions. PMID- 21009708 TI - Cytological studies in Culex; diploid and meiotic divisions. PMID- 21009710 TI - Metabolism and motility of spermatozoa. PMID- 21009709 TI - The selective elimination of inversion dicentric chromatids during meiosis in the eggs of Sciara impatiens. PMID- 21009711 TI - Intramural hospital contraceptive clinics. PMID- 21009712 TI - EUGENIC sterilization in North Carolina. PMID- 21009713 TI - MOHAMMEDAN population. PMID- 21009714 TI - Commercially available mechanical devices for use in contraception. PMID- 21009716 TI - FREUD on contraception. PMID- 21009715 TI - Psychosomatic problems in fertility. PMID- 21009717 TI - USE of estrogens in the control of conception. PMID- 21009718 TI - BASAL temperature charts. PMID- 21009719 TI - [Not Available]. PMID- 21009720 TI - [Not Available]. PMID- 21009721 TI - [Not Available]. PMID- 21009723 TI - Past memories. PMID- 21009722 TI - Uterus didelphys. PMID- 21009724 TI - Toxaemias of pregnancy in Kashmir. PMID- 21009725 TI - Uterine haemorrhage without demonstrable pathology. PMID- 21009726 TI - Some congenital deformities; their treatment and prognosis. PMID- 21009727 TI - Midwives and medical aid. PMID- 21009728 TI - [Not Available]. PMID- 21009729 TI - [Not Available]. PMID- 21009730 TI - [Not Available]. PMID- 21009732 TI - [Not Available]. PMID- 21009731 TI - [Not Available]. PMID- 21009734 TI - [Not Available]. PMID- 21009733 TI - [Not Available]. PMID- 21009735 TI - Sulfa drugs and penicillin in pyogenic meningitis. PMID- 21009736 TI - Electrical measurements of the healing rate of human skin. PMID- 21009738 TI - Some thoughts on the status of gastric surgery in peptic ulcer. PMID- 21009737 TI - Influence of ephedrine sulfate on blood pressure in hypertensive rats. PMID- 21009739 TI - SOME interesting animal parasites. PMID- 21009740 TI - HEALTH insurance awaits taxing decisions. PMID- 21009741 TI - The old becomes the new. PMID- 21009742 TI - Life begins in safety in this remodeled nursery. PMID- 21009743 TI - Venereal disease control. PMID- 21009744 TI - Efficiency and economy should determine nursing needs. PMID- 21009745 TI - Redwoods form the background for the new Trinity Hospital. PMID- 21009746 TI - Should America have compulsory health insurance? PMID- 21009747 TI - Chronic disease from a patient's point of view. PMID- 21009748 TI - How Buffalo fought polio. PMID- 21009749 TI - The treatment of diabetics. PMID- 21009751 TI - The G.I. and hospital pharmacy. PMID- 21009750 TI - Bed rest in tuberculosis. PMID- 21009752 TI - How to use DDT. PMID- 21009753 TI - [Not Available]. PMID- 21009754 TI - [Not Available]. PMID- 21009755 TI - [Not Available]. PMID- 21009756 TI - [Not Available]. PMID- 21009758 TI - [Not Available]. PMID- 21009757 TI - [Not Available]. PMID- 21009759 TI - [Not Available]. PMID- 21009760 TI - [Not Available]. PMID- 21009761 TI - [Not Available]. PMID- 21009762 TI - [Not Available]. PMID- 21009763 TI - [Not Available]. PMID- 21009764 TI - [Not Available]. PMID- 21009765 TI - [Not Available]. PMID- 21009767 TI - Scrub typhus fever (Tsutsugamushi disease) in New Guinea; report of 75 cases. PMID- 21009766 TI - Prefrontal lobotomy; survey of 331 cases. PMID- 21009768 TI - The clinical significance of cold hemagglutinins. PMID- 21009769 TI - Clinical arrest in enterococcal endocarditis. PMID- 21009770 TI - The use of a modified globin from human erythrocytes in hypoproteinemias. PMID- 21009771 TI - Fatal agranulocytosis with autopsy following the use of thiouracil in a case of thyrotoxicosis. PMID- 21009772 TI - The therapeutic value of early physical activity in rheumatic fever; preliminary report. PMID- 21009774 TI - Palmar erythema; its relationship to protein deficiency. PMID- 21009773 TI - The relationship of blood pressure and serum thiocyanate. PMID- 21009775 TI - A simplified apparatus for the induction of artificial pneumoperitoneum. PMID- 21009776 TI - The occurrence of fibrinolysis in shock, with observations on the prothrombin time and the plasma fibrinogen during hemorrhagic shock. PMID- 21009777 TI - Observations on the specificity and clinical use of Dirofilaria immitis antigen in the diagnosis of human filariasis (Wuchereria bancrofti). PMID- 21009778 TI - The treatment of bacillary dysentery in Chinese soldiers with sulfaguanidine and sulfadiazine. PMID- 21009779 TI - Infectious polyneuritis (Guillain-Barre syndrome). PMID- 21009780 TI - Cranial arteritis; a critical evaluation of the syndrome of temporal arteritis with report of a case. PMID- 21009781 TI - Polyarteritis nodosa; report of 11 cases with review of recent literature. PMID- 21009782 TI - Some unusual thoracic complications of typhoid and Salmonella infections. PMID- 21009783 TI - A study of one hundred cases with a positive coccidioidin skin test. PMID- 21009784 TI - Short P-R interval, prolonged QRS complex (Wolff, Parkinson, White syndrome); report of fourteen cases and a review of the literature. PMID- 21009785 TI - Liver function studies in diabetes mellitus. PMID- 21009786 TI - What can be accomplished in the treatment of heart diseases. PMID- 21009787 TI - An apparatus for the introduction of penicillin aerosol into the nasal accessory sinuses with a case report of a patient with chronic sinusitis. PMID- 21009788 TI - Acute hemolytic anemia due to neoarsphenamine; report of a fatal case. PMID- 21009789 TI - The syndrome of compression of the pulmonary artery by a syphilitic aortic aneurysm with or without arterio-arterial communication. PMID- 21009790 TI - Paroxymal ventricular tachycardia occurring in the absence of demonstrable heart disease. PMID- 21009791 TI - Electrocardiographic changes following heat stroke; report of a case. PMID- 21009792 TI - PH factor. PMID- 21009793 TI - Modern conceptions in the treatment of inguinal hernia. PMID- 21009794 TI - Sulphathiazole (cibazol) in diarrhoeic conditions. PMID- 21009795 TI - A short note on the practical measures against plague. PMID- 21009796 TI - Atebrine brand of amyl-acridine derivative in human malaria. PMID- 21009798 TI - Baby's cry and its significations. PMID- 21009797 TI - Cancrum oris. PMID- 21009799 TI - Vertigo and its importance in diagnosis. PMID- 21009800 TI - Urine as an aid to diagnosis. PMID- 21009801 TI - Glaucoma. PMID- 21009802 TI - Anaemia in tea gardens. PMID- 21009803 TI - Cancrum oris and some other types of stomatitis. PMID- 21009804 TI - Diseases mentioned in the 17th and 18th century records of Fort St. George. PMID- 21009805 TI - Penicillin for human foot and mouth disease. PMID- 21009806 TI - Teratodymes, monosomians. PMID- 21009807 TI - An interesting case of fowl-poisoning. PMID- 21009808 TI - A case of round-worms complicated with malaria. PMID- 21009809 TI - Malaria with strange history. PMID- 21009810 TI - [On the concomitant change of excitability in the nerve in parabiosis by pressure]. PMID- 21009811 TI - [The action of the muscles on the nerves and on the cerebro-spinal centres; myogenetic analysis and functional observations]. PMID- 21009812 TI - [The rate of regeneration of the peripheral nerves in mammalia; second communication]. PMID- 21009813 TI - [Polarizational effect on the nerve commissure of anodent under the action of acetylcholin]. PMID- 21009814 TI - [On the current of action of the frog's sartorius]. PMID- 21009816 TI - [Chronaxia and rheobase of the eye in gunshot damages of the optical routes]. PMID- 21009815 TI - [Refractoriness of muscle on direct and indirect irritation]. PMID- 21009818 TI - [On shock as a neuro-distrophic process and on its treatment]. PMID- 21009819 TI - [On the pathogenesis of traumatic shock]. PMID- 21009817 TI - [The effect of the stimulator-schizandra on neuro-muscular excitability in man]. PMID- 21009820 TI - [Blood changes in burn shock]. PMID- 21009821 TI - [Biologically active substances in the exudation of tuberculous pleurisy]. PMID- 21009822 TI - [On the activation of the mesenchyma in acute inflammation]. PMID- 21009823 TI - [The state of the secretory and motor functions of the digestive tract on immediate action of kalium and calcium on the nerve centres]. PMID- 21009824 TI - [The secretory activity of the pancreas under reduced barometric pressure]. PMID- 21009825 TI - [On the effect of hypoxemia on the oxidation processes in the organism]. PMID- 21009826 TI - [The changes of the oxidation ratio of the blood and urine in various stages of Brown-Pearce's cancer development]. PMID- 21009827 TI - [On the role of the liver in autoregulation of the blood sugar level; the liver function in depancreatized and epinephrectomized animals]. PMID- 21009828 TI - [On the correspondence of the degree of resorption of the tadpole larval organs with the level of thyroid gland, activated by thyrectropic hormone]. PMID- 21009829 TI - [Participation of the hypophysis, parathyroid glands, bones and vitamin D in determination of the calcium level in the blood of animals]. PMID- 21009830 TI - [Experiment in the morphological analysis of the rami of the nervi intercostales of the diaphragm]. PMID- 21009831 TI - [Experimental data regarding the influence of the electric field on the microflora of metallic foreign bodies in the organism]. PMID- 21009832 TI - [On the nature of the chemical receptors of the sinus carotici; the action of natrium acid on the sinus carotici]. PMID- 21009833 TI - [On the method of separate registration in situ of the musculi longitudinales et circulares of the small intestines]. PMID- 21009834 TI - Medicine and the State, with special reference to the Emergency Medical Service. PMID- 21009835 TI - The relation between congenital obliteration of the bile ducts and icterus gravis neonatorum. PMID- 21009836 TI - The Rh factor and blood transfusion; observations on a group of Rh-negative individuals transfused with Rh positive blood. PMID- 21009837 TI - Asymptomatic kala-azar in soldiers from over-seas. PMID- 21009838 TI - Four cases of Russell's viper bite. PMID- 21009839 TI - Blindness following haematemesis. PMID- 21009840 TI - Anaesthesia and blood transfusion in 14 cases of traumatic aneurysm. PMID- 21009841 TI - Local penicillin in purulent pericarditis. PMID- 21009842 TI - Treatment of varicose ulcers. PMID- 21009844 TI - Synthetic substitutes for quinidine. PMID- 21009843 TI - The contribution of anatomy to the war. PMID- 21009845 TI - Poisoning by Amanita phalloides. PMID- 21009846 TI - The solubility of sulphonamides in relation to hydrogen-ion concentration. PMID- 21009847 TI - Penicillin cream of low concentration. PMID- 21009848 TI - Intestinal hernia between folds of broad ligament. PMID- 21009849 TI - Dermatitis due to sulphaguanidine. PMID- 21009850 TI - Effect on troops of the V weapon bombardment of Antwerp. PMID- 21009851 TI - [Not Available]. PMID- 21009852 TI - [Not Available]. PMID- 21009853 TI - [Not Available]. PMID- 21009854 TI - [Not Available]. PMID- 21009855 TI - [Not Available]. PMID- 21009856 TI - [Not Available]. PMID- 21009857 TI - [Not Available]. PMID- 21009858 TI - [Not Available]. PMID- 21009859 TI - [Not Available]. PMID- 21009860 TI - [Not Available]. PMID- 21009861 TI - [Not Available]. PMID- 21009862 TI - [Not Available]. PMID- 21009863 TI - [Not Available]. PMID- 21009864 TI - [Not Available]. PMID- 21009865 TI - [Not Available]. PMID- 21009866 TI - [Not Available]. PMID- 21009867 TI - Androgen therapy in coronary disease; preliminary report. PMID- 21009868 TI - Face presentation. PMID- 21009869 TI - Rupture of the uterus. PMID- 21009870 TI - Brow presentation; case report. PMID- 21009871 TI - Sterility and prevention of conception. PMID- 21009872 TI - Blood groups and transfusion. PMID- 21009873 TI - Treatment of malaria in general practice. PMID- 21009874 TI - Ophthalmology in India. PMID- 21009876 TI - Importance of psychology in practice of medicine. PMID- 21009875 TI - Typhoid fever. PMID- 21009877 TI - VITAMIN A requirements experiments in Britain. PMID- 21009878 TI - A preliminary survey for the detection of intestinal pathogens among the pickled vegetables in Chengtu. PMID- 21009879 TI - A survey of 200 samples of pickles in Chengtu for intestinal pathogens. PMID- 21009880 TI - A study of infant mortality in Kweichow. PMID- 21009881 TI - Report of an investigation of infant mortality and its causes in Pishan. PMID- 21009882 TI - Chemotherapy of typhoid fever; a preliminary report of 11 cases treated with a combination of sulfathiazole and sulfaguanidine. PMID- 21009883 TI - A simple dark adaptometer. PMID- 21009884 TI - Vitamin A nutrition of Chengtu medical students. PMID- 21009885 TI - Type of prepuce and distribution of pubic hair in Chinese. PMID- 21009886 TI - Hydrosalpinx. PMID- 21009887 TI - Portable surgical hospital in northern Burma. PMID- 21009888 TI - A simple spirometer. PMID- 21009889 TI - Genito-urinary calculi. PMID- 21009890 TI - Phlegmonous gastritis. PMID- 21009891 TI - Neoplasm of the lungs. PMID- 21009892 TI - Psychoneurotic aspects of gastrointestinal diseases. PMID- 21009893 TI - Ambulatory electroschock therapy; its employment for patients seen by the general practitioner. PMID- 21009894 TI - The hypertonic infant. PMID- 21009895 TI - Rheumatic fever; pathological changes. PMID- 21009896 TI - Staphylectomy for colds and sinusitis. PMID- 21009897 TI - A new improved inhaler. PMID- 21009898 TI - Tropical medicine. PMID- 21009899 TI - Functional uterine bleeding: a case history. PMID- 21009900 TI - [Not Available]. PMID- 21009901 TI - [Not Available]. PMID- 21009902 TI - [Not Available]. PMID- 21009903 TI - [Not Available]. PMID- 21009904 TI - [Not Available]. PMID- 21009905 TI - The numbers and the sites of origin of the droplets expelled during expiratory activities. PMID- 21009906 TI - War wounds and injuries involving the paranasal air sinuses. PMID- 21009907 TI - The standardisation of liver extracts for intramuscular injection. PMID- 21009908 TI - Blood culture: methods and results. PMID- 21009909 TI - Despatch of material for histological examination. PMID- 21009910 TI - [Not Available]. PMID- 21009911 TI - [Not Available]. PMID- 21009912 TI - [Not Available]. PMID- 21009913 TI - [Not Available]. PMID- 21009914 TI - Tuberculous disease of the kidney. PMID- 21009915 TI - Tuberculosis of the male genital tract. PMID- 21009916 TI - Menstruation. PMID- 21009917 TI - Mumu; a few facts about filariasis for folks who fear that filaria-infected fellows will fetch filariae from the front. PMID- 21009918 TI - Congenital anomalies of the coronary arteries. PMID- 21009919 TI - Gastrojejunal ulcer as related to gastro-enterostomy. PMID- 21009920 TI - Bronchiectasis. PMID- 21009921 TI - Diagnosis and treatment of lung abscess and acute empyema. PMID- 21009922 TI - Hemorrhage from Meckel's diverticulum in infancy; report of a case. PMID- 21009923 TI - Circumscribed neurodermatitis. PMID- 21009924 TI - [Not Available]. PMID- 21009925 TI - [Not Available]. PMID- 21009926 TI - [Not Available]. PMID- 21009927 TI - [Not Available]. PMID- 21009928 TI - [Not Available]. PMID- 21009929 TI - [Not Available]. PMID- 21009930 TI - [Not Available]. PMID- 21009931 TI - [Not Available]. PMID- 21009932 TI - [Not Available]. PMID- 21009933 TI - [Not Available]. PMID- 21009934 TI - [Not Available]. PMID- 21009935 TI - [Not Available]. PMID- 21009936 TI - [Not Available]. PMID- 21009937 TI - [Not Available]. PMID- 21009938 TI - [Not Available]. PMID- 21009939 TI - [Not Available]. PMID- 21009941 TI - [Not Available]. PMID- 21009940 TI - [Not Available]. PMID- 21009942 TI - [Not Available]. PMID- 21009943 TI - [Not Available]. PMID- 21009944 TI - [Not Available]. PMID- 21009945 TI - [Not Available]. PMID- 21009946 TI - [Not Available]. PMID- 21009947 TI - [Not Available]. PMID- 21009948 TI - [Not Available]. PMID- 21009949 TI - [Not Available]. PMID- 21009950 TI - [Not Available]. PMID- 21009951 TI - [Not Available]. PMID- 21009952 TI - [Not Available]. PMID- 21009953 TI - [Not Available]. PMID- 21009954 TI - [Not Available]. PMID- 21009955 TI - [Not Available]. PMID- 21009956 TI - [Not Available]. PMID- 21009957 TI - [Not Available]. PMID- 21009958 TI - [Not Available]. PMID- 21009959 TI - [Not Available]. PMID- 21009960 TI - [Not Available]. PMID- 21009961 TI - [Not Available]. PMID- 21009962 TI - [Not Available]. PMID- 21009964 TI - [Not Available]. PMID- 21009963 TI - [Not Available]. PMID- 21009965 TI - [Not Available]. PMID- 21009966 TI - [Not Available]. PMID- 21009967 TI - [Not Available]. PMID- 21009968 TI - [Not Available]. PMID- 21009969 TI - [Not Available]. PMID- 21009970 TI - [Not Available]. PMID- 21009971 TI - A case of canine S. typhimurium infection with notes on other salmonella infections in animals. PMID- 21009972 TI - A survey of latent diphtheria in Vizagapatam. PMID- 21009973 TI - Aetiology and treatment of ulcus tropicum. PMID- 21009974 TI - Investigations of ground-water pollution; soil characteristic in West Bengal, India, at the site of ground-water pollution investigations. PMID- 21009975 TI - Investigations of ground-water pollution; ground-water in West Bengal, India. PMID- 21009976 TI - Studies on the destruction of vitamin A in shark-liver oil; relation between vitamin A destruction and peroxide number. PMID- 21009977 TI - Studies on the destruction of vitamin A in shark-liver oil; catalytic activity of metals. PMID- 21009978 TI - The growth-promoting value of eggs; supplementary value of eggs and pulses in a Bengali diet. PMID- 21009979 TI - Biological value of proteins from muscle meat of cow, buffalo and goat. PMID- 21009980 TI - The food value of a further batch of edibles; estimated by chemical methods. PMID- 21009981 TI - Studies on calcium and phosphorus metabolism; calcium, phosphorus and phytin contents of the diets of Kangra valley and their relation to nutrition. PMID- 21009982 TI - Studies on calcium and phosphorus metabolism; blood-serum calcium, phosphorus and phosphatase of the population of Kangra valley. PMID- 21009983 TI - Studies on calcium and phosphorus metabolism; hepatic inefficiency and rickets. PMID- 21009984 TI - Dental and osseous changes in spontaneous fluorosis in rats. PMID- 21009985 TI - Assay of anthracene purgatives by the estimation of the content of hydroxymethylanthraquinones. PMID- 21009986 TI - On the preparation of liquor adrenaline hydrochloridi. PMID- 21009987 TI - Inula royleana DC; its chemistry and pharmacological action. PMID- 21009988 TI - Glycolysis in diabetic blood and its significance. PMID- 21009989 TI - On the assay of urea stibamine. PMID- 21009990 TI - Chemistry and pharmacology of some common indigenous remedies. PMID- 21009991 TI - Haematological studies in Silenus (Macacus) rhesus; nature of malarial anaemia in monkeys. PMID- 21009992 TI - Spectra of haemochromogen and cyanhaemochromogen. PMID- 21009993 TI - Filarial infection in Dhamda (Drug District, C.P.) due to Wuchereria malayi. PMID- 21009994 TI - Chronic endemic fluorosis (with bone affections) in the Punjab. PMID- 21009995 TI - An outbreak of typhus fever (OXK) in India. PMID- 21009996 TI - One hundred and fourteen cases of typhus fever seen in an Indian military hospital in Calcutta. PMID- 21009997 TI - Infective hepatitis; analysis of 100 cases in the Army. PMID- 21009998 TI - Hepatic abscess secondarily infected; penicillin treatment. PMID- 21009999 TI - Acute polyarteritis nodosa in a case of malaria. PMID- 21010000 TI - Intestinal fuso-spirochaetosis. PMID- 21010001 TI - The presence of rhinoscleroma in Koraput District of southern Orissa. PMID- 21010002 TI - Mepacrine intoxication and vitamin B deficiency. PMID- 21010003 TI - A suggested first-aid treatment for cobra bite with carbolic soap solution. PMID- 21010004 TI - A case of septicaemia treated with penicillin after failure of sulphonamide therapy. PMID- 21010005 TI - Two cases of strangulated hernia. PMID- 21010006 TI - Nitritoid crises after intravenous injections. PMID- 21010007 TI - JAUNDICE and other diseases transmitted by needles and syringes. PMID- 21010008 TI - Shock and refrigeration. PMID- 21010009 TI - The treatment of cirrhosis of the liver with choline and cystine. PMID- 21010010 TI - Reaction following bronchography with iodized oil. PMID- 21010011 TI - Toxic manifestations associated with prolonged ertron ingestion. PMID- 21010012 TI - Effect of penicillin on course of early syphilis. PMID- 21010013 TI - Recovery from pulmonary moniliasis following serum therapy. PMID- 21010014 TI - Radium. PMID- 21010015 TI - Hospital residencies under the G.I.Bill. PMID- 21010016 TI - The status of the English doctor. PMID- 21010017 TI - Overtreatment dermatitis of the feet. PMID- 21010018 TI - Streptococcus in subacute bacterial endocarditis. PMID- 21010019 TI - Nocturnal gastric secretion in duodenal ulcer; studies on normal subjects and patients, with their bearing on ulcer management. PMID- 21010020 TI - Physostigmine for muscle spasm in rheumatoid arthritis. PMID- 21010021 TI - Traumatic rupture of the spleen in childhood. PMID- 21010022 TI - Colloidal salt nasal tamponades; their use and abuse. PMID- 21010023 TI - Fracture of the first cervical vertebra, complicated by cervical rib. PMID- 21010024 TI - PRESS comment on compulsory sickness insurance. PMID- 21010025 TI - Appointment and tenure of faculty of professorial rank. PMID- 21010026 TI - What the educator thinks the ideal medical curriculum should be. PMID- 21010027 TI - Tradition, the rivet in the curriculum. PMID- 21010028 TI - Embryology in the medical curriculum. PMID- 21010029 TI - Distribution of medical college students by residence. PMID- 21010030 TI - The challenge to pharmacology. PMID- 21010031 TI - Epidemic of acute respiratory disease associated with atypical pneumonia. PMID- 21010032 TI - The effect of alternations in blood volume on the anemia and hypoproteinemia of human malaria. PMID- 21010033 TI - Chemical, clinical and immunological studies on the products of human plasma fractionation; serum albumin as a diluent for Rh typing reagents. PMID- 21010034 TI - Chemical, clinical, and immunological studies on the products of human plasma fractionation; the use of salt-poor concentrated human serum albumin solution in the treatment of chronic Bright's disease. PMID- 21010035 TI - The toxic factors in experimental traumatic shock; physiologic effects of muscle ligation in the dog. PMID- 21010036 TI - The toxic factors in experimental traumatic shock; studies on electrolyte and water balance in shock. PMID- 21010037 TI - The toxic factors in experimental traumatic shock; shock accompanying muscle ischemia and loss of vascular fluid. PMID- 21010038 TI - The toxic factors in experimental traumatic shock; the effects of the intravenous injection of the effusion from ischemic muscle. PMID- 21010039 TI - The toxic factors in experimental traumatic shock; chemical and enzymatic properties of muscle exudate. PMID- 21010040 TI - The toxic factors in experimental traumatic shock; the toxic influence of the bacterial flora, particularly Clostridium welchii, in exudates of ischemic muscle. PMID- 21010041 TI - Some observations on the effect of injected cytochrome C in animals. PMID- 21010042 TI - Effect of iodine on the thyroid gland in Graves' disease when given in conjunction with thiouracil; a two-action theory of iodine. PMID- 21010044 TI - The estimation of hepatic blood flow in man. PMID- 21010043 TI - Circulation and respiration during an episode of chill and fever in man. PMID- 21010045 TI - The absorption and excretion of streptomycin in human chronic typhoid carriers. PMID- 21010046 TI - Studies on the chemical nature of the substance inducing transformation of pneumococcal types; effect of desoxyribonuclease on the biological activity of the transforming substance. PMID- 21010047 TI - Studies on the chemical nature of the substance inducing transformation on pneumococcal types; an improved method for the isolation of the transforming substance and its application to Pneumococcus Types II, III, and VI. PMID- 21010048 TI - Studies on pneumonia virus of mice (PVM); hemagglutination by the virus; the occurrence of combination between the virus and a tissue substance. PMID- 21010049 TI - Studies on scrub typhus; soluble antigen in tissues and body fluids of infected mice and rats. PMID- 21010050 TI - Formation of serologically reactive dextrans by streptococci from subacute bacterial endocarditis. PMID- 21010051 TI - Alkaline phosphatase activity in normal and abnormal human blood and bone marrow cells. PMID- 21010052 TI - The effects of adrenalin and nembutal anesthesia on blood constituents before and after splenectomy. PMID- 21010053 TI - Pectin excretion studies in the human being. PMID- 21010054 TI - The use of the copper sulfate method of hemoglobin estimation for screening blood donors. PMID- 21010055 TI - Studies on cultivation of rickettsiae in eggs. PMID- 21010056 TI - Liver functional impairment in therapeutic malaria with particular reference to the unsuccessful use of methionine as a protective agent. PMID- 21010057 TI - The formation and excretion of acetylated sulfonamides. PMID- 21010058 TI - Miscellaneous pharmacologic actions of citrinin. PMID- 21010059 TI - Effect of synthetic vitamin K and of quinine sulfate on the prothrombin level. PMID- 21010060 TI - Depression of gamma globulin in hypoproteinemia due to malnutrition. PMID- 21010061 TI - The inability of cysteine to inactivate penicillin in the presence of broth and blood. PMID- 21010062 TI - A photoelectric method for the determination of cholesterol in urine. PMID- 21010063 TI - On the estimation of arterial carbon dioxide from samples of cutaneous (capillary) blood. PMID- 21010064 TI - Serology and obstetrics. PMID- 21010065 TI - Free plasma service in North Dakota. PMID- 21010066 TI - Short leg backache. PMID- 21010067 TI - Some common skin diseases and their treatment. PMID- 21010068 TI - A note on diphtheria with special reference to Eire. PMID- 21010070 TI - The medical population of Ireland. PMID- 21010069 TI - States of anxiety. PMID- 21010071 TI - [Not Available]. PMID- 21010072 TI - [Not Available]. PMID- 21010073 TI - [Not Available]. PMID- 21010074 TI - [Not Available]. PMID- 21010075 TI - [Not Available]. PMID- 21010076 TI - The role of castration as auxiliary treatment in carcinoma of the breast; report of a case. PMID- 21010077 TI - The role of infection in thyroid crisis. PMID- 21010078 TI - A hitherto underscribed anomaly of the extra-hepatic bile ducts and blood vessels and its surgical implications. PMID- 21010079 TI - A case of chronic metastatic abscess of the costal cartilage due to Bacillus pyocyaneus. PMID- 21010080 TI - Essays on the biology of disease. PMID- 21010081 TI - Life's later years; studies in the medical history of old age. PMID- 21010082 TI - Pneumococcus meningitis; treatment with penicillin and sulfenamide. PMID- 21010084 TI - Frontiers of mental hygiene. PMID- 21010083 TI - Topical application of penicillin. PMID- 21010085 TI - The diagnosis and management of some common cardiac arrhythmias. PMID- 21010086 TI - Remarks for health service. PMID- 21010087 TI - CAMPAIGN against cancer. PMID- 21010088 TI - Medicine then and now. PMID- 21010089 TI - Should cysts of the breast be aspirated? PMID- 21010090 TI - The management of surgical complications of appendicitis. PMID- 21010091 TI - Elongated uvula. PMID- 21010092 TI - Medicine and social changes. PMID- 21010093 TI - [Not Available]. PMID- 21010094 TI - [Not Available]. PMID- 21010095 TI - [Not Available]. PMID- 21010096 TI - [Not Available]. PMID- 21010098 TI - [Not Available]. PMID- 21010097 TI - [Not Available]. PMID- 21010099 TI - [Not Available]. PMID- 21010100 TI - [Not Available]. PMID- 21010101 TI - [Not Available]. PMID- 21010103 TI - [Not Available]. PMID- 21010102 TI - [Not Available]. PMID- 21010104 TI - [Not Available]. PMID- 21010105 TI - Speech and handedness. PMID- 21010106 TI - Symptoms of early pulmonary tuberculosis. PMID- 21010107 TI - Penicillin treatment of serous-cavity infections. PMID- 21010108 TI - Varicose veins; precipitation method of treatment. PMID- 21010109 TI - Target-cell anaemia; two cases in Bucharan Jews. PMID- 21010110 TI - MICROFILM AND MEDICAL LITERATURE. PMID- 21010111 TI - Fatty liver and malignant malnutrition. PMID- 21010113 TI - Effect of some antibiotics on pathogenic fungi. PMID- 21010112 TI - Subacute necrosis of the liver without icterus. PMID- 21010114 TI - Mycophenolic acid; an antibiotic from Penicillium brevicompactum Dlerckx. PMID- 21010115 TI - Surgery in malaria. PMID- 21010116 TI - Hepatitis after penicillin injections. PMID- 21010117 TI - Foetal dysplasia of leg; a new operative approach. PMID- 21010118 TI - Penicillin in gonorrhoea. PMID- 21010119 TI - The action of relaxin in the mouse. PMID- 21010120 TI - Stress incontinence. PMID- 21010121 TI - MEDICINE in Germany. PMID- 21010122 TI - MALNUTRITION in Belgium. PMID- 21010123 TI - Socio-medical surveys. PMID- 21010124 TI - MEDICAL services of Norway. PMID- 21010125 TI - The London Hospital in the war. PMID- 21010126 TI - Some experiences and reactions as a prisoner of war in German hands. PMID- 21010127 TI - Varicose veins of the lower limb. PMID- 21010128 TI - Medical ailments amongst the Zulus. PMID- 21010130 TI - Modern concept of the management of cough. PMID- 21010129 TI - Estimation of haemoglobin. PMID- 21010131 TI - Abrief history of varicose vein therapy. PMID- 21010132 TI - On the evolution of infant feeding, in health and in disease. PMID- 21010133 TI - The pneumoconioses. PMID- 21010134 TI - Aeroneurosis and air sickness. PMID- 21010135 TI - American medicine at the crossroads. PMID- 21010136 TI - The syndrome of premature ventricular excitation in which the PR interval is short and the QRS complex is prolonged (Wolff-Parkinson-White syndrome); report of four cases. PMID- 21010137 TI - The toxicity and potential dangers of DDT to humans and warm-blooded animals. PMID- 21010138 TI - A study to determine the antibacterial efficiency of combined tyrothricin and sulfadiazine. PMID- 21010139 TI - The successful use of oral penicillin in the treatment of subacute bacterial endocarditis; report of a case. PMID- 21010140 TI - Treatment of cancer. PMID- 21010141 TI - Diagnosis of spinal tumour. PMID- 21010142 TI - The growth of pediatrics in the Chicago area. PMID- 21010143 TI - Skin conditions in the newborn. PMID- 21010144 TI - Rheumatic fever, diagnostic criteria, and rheumatic heart disease. PMID- 21010145 TI - The clinical significance of heart murmurs in children. PMID- 21010146 TI - Whooping cough; prevention and treatment. PMID- 21010147 TI - Immune serum in the prophylaxis and treatment of virus diseases. PMID- 21010148 TI - Jaundice in the newborn. PMID- 21010149 TI - The anemias of childhood. PMID- 21010150 TI - Recurrent parotitis. PMID- 21010151 TI - Bronchial obstruction in infants and children. PMID- 21010152 TI - Breast enlargement in pediatric practice. PMID- 21010153 TI - Acute hematogenous osteomyelitis in infancy. PMID- 21010155 TI - Fears in children. PMID- 21010154 TI - Flat feet in children. PMID- 21010156 TI - Convulsions in infancy and childhood. PMID- 21010157 TI - Neuropsychiatric symptoms in acute infections of childhood. PMID- 21010158 TI - Precocious sexual development in children. PMID- 21010159 TI - The physician and his opportunities for service to the underprivileged and handicapped children in his state. PMID- 21010160 TI - A new method of treatment of Dupuytren's contracture, a form of fibrositis. PMID- 21010162 TI - The problem of crime. PMID- 21010161 TI - Some unfortunate public health aspects of gonorrhea control. PMID- 21010163 TI - Deliquency, split mind, magistrate, doctor and parent. PMID- 21010164 TI - A month in Holloway. PMID- 21010165 TI - The normal infant. PMID- 21010166 TI - Treatment of acute urinary retention. PMID- 21010167 TI - Pandemic malnutrition. PMID- 21010169 TI - A new conception of diaphragmatic hernia. PMID- 21010168 TI - Medical education, research and practice in relation to industrial health. PMID- 21010170 TI - The management of genitourinary infections and essential hypertension. PMID- 21010171 TI - Some newer concepts of hypertension; a summary of the literature. PMID- 21010172 TI - Fecal impaction complicated by undetected malignancy and coma; report of a case. PMID- 21010173 TI - A therapeutic study of bronchial asthma. PMID- 21010174 TI - The syphilitic brain and human destinies. PMID- 21010175 TI - Management of thrombophlebitis; case reports. PMID- 21010176 TI - Irritable colon; experience with 122 cases in an Army general hospital. PMID- 21010177 TI - Hypertension. PMID- 21010178 TI - The chemical basis of inheritance. PMID- 21010179 TI - Ambulatory paraplegia. PMID- 21010180 TI - The future of artificial insemination. PMID- 21010181 TI - RICKETS. PMID- 21010182 TI - Sore throat. PMID- 21010183 TI - The bacteriostatic capacity of acrylic acid compounds. PMID- 21010184 TI - Hodgkin's disease; clinical diagnosis. PMID- 21010185 TI - Mental breaking points. PMID- 21010186 TI - The incidence of leukemia in radiologists. PMID- 21010187 TI - Ice cream as a source of riboflavin, carotene and ascorbic acid. PMID- 21010188 TI - Sporotrichosis; report of a case. PMID- 21010189 TI - Problems in the distribution of medical care. PMID- 21010190 TI - Nephrolithiasis. PMID- 21010191 TI - Malignant lymphoma, Hodgkin's sarcoma type, involving cervical and retroperitoneal lymph nodes, spleen and bone marrow. PMID- 21010192 TI - Progress in the treatment of subacute bacterial endocarditis. PMID- 21010193 TI - Acute obstruction of the small intestine; a report of one hundred and eighteen cases. PMID- 21010194 TI - Epistaxis. PMID- 21010196 TI - Health-insurance plans. PMID- 21010195 TI - Cardiovascular disease among veterans of World War II; a survey of 19,870 cases. PMID- 21010197 TI - Subacute bacterial endocarditis. PMID- 21010198 TI - Tuberculosis of spine. PMID- 21010199 TI - Carcinoma of the cervix; an attempted follow-up study of 500 cases; analysis of material. PMID- 21010200 TI - The treatment of carcinoma of the cervix at Charity Hospital; analysis of 716 cases; three-year and five-year end results. PMID- 21010201 TI - Some hazards of anesthesia. PMID- 21010202 TI - A tuberculosis survey in New Orleans. PMID- 21010203 TI - A report on terminal obstetrical anesthesia using low spinal block. PMID- 21010204 TI - Mediterranean anemia; report of a case in a Negro. PMID- 21010205 TI - Narcosynthesis under sodium amytal; adjunct to psychiatric diagnosis and treatment. PMID- 21010206 TI - Treatment of supracondylar fractures of humerus in childhood. PMID- 21010207 TI - Disability evaluation of the injured extremity. PMID- 21010208 TI - The intrasternal route in acute circulatory failure. PMID- 21010209 TI - Extrauterine pregnancy; a five year study. PMID- 21010210 TI - An effective control program for rabies. PMID- 21010211 TI - The possibility of exterminating mammary carcinoma in mice by a simple preventive measure; its practical implication for human pathology. PMID- 21010213 TI - Destructive granuloma of bone in the skull. PMID- 21010212 TI - Thrombophlebitis and phlebothrombosis. PMID- 21010214 TI - An extreme case of alkalosis with necropsy findings. PMID- 21010215 TI - Increased intracranial pressure and the general practitioner's responsibility. PMID- 21010216 TI - Tantalum cranioplasty. PMID- 21010217 TI - Progress and stasis in medicine; perforation of colon by a chicken bone. PMID- 21010218 TI - Case report of congenital right diaphragmatic hernia with autopsy findings. PMID- 21010219 TI - A case of perforative diverticulitis of the colon in a 27 year old male. PMID- 21010220 TI - Soil in relation to health. PMID- 21010221 TI - Addison's disease: report of a case and an analysis of autopsied cases of tuberculosis of the adrenal glands. PMID- 21010222 TI - Cholera infantum. PMID- 21010223 TI - Carcinoma of the colon in rural Pennsylvania. PMID- 21010224 TI - Fusospirochetal pulmonary abscess; clinical report of a case. PMID- 21010225 TI - A movement for improvement in health and physical fitness; what role should we play in Pennsylvania? PMID- 21010226 TI - MEDICAL service plan of the Medical Service Association of Pennsylvania. PMID- 21010227 TI - Recent advances in knowledge of the Rh blood factors, with special reference to the clinical applications. PMID- 21010228 TI - The tuberculosis service in the National Health Service. PMID- 21010229 TI - Delayed closure of compound fracture wounds. PMID- 21010230 TI - [Not Available]. PMID- 21010231 TI - [Not Available]. PMID- 21010232 TI - [Not Available]. PMID- 21010233 TI - [Not Available]. PMID- 21010234 TI - [Not Available]. PMID- 21010235 TI - [Not Available]. PMID- 21010236 TI - [Not Available]. PMID- 21010237 TI - [Not Available]. PMID- 21010238 TI - [Not Available]. PMID- 21010239 TI - [Not Available]. PMID- 21010240 TI - [Not Available]. PMID- 21010241 TI - [Not Available]. PMID- 21010242 TI - [Not Available]. PMID- 21010243 TI - [Not Available]. PMID- 21010244 TI - [Not Available]. PMID- 21010245 TI - [Not Available]. PMID- 21010246 TI - [Not Available]. PMID- 21010247 TI - [Not Available]. PMID- 21010248 TI - [Not Available]. PMID- 21010249 TI - [Not Available]. PMID- 21010250 TI - [Not Available]. PMID- 21010251 TI - The modern treatment of cancer. PMID- 21010252 TI - Report of biliary surgery for 1942, 1943 and 1944. PMID- 21010253 TI - Brucellosis and peptic ulcer. PMID- 21010254 TI - Extensive resection of perforating carcinoma of the stomach with abscess. PMID- 21010255 TI - Report of surgery of the stomach and duodenum for 1944. PMID- 21010256 TI - Hypertension. PMID- 21010257 TI - The training of clinical teachers. PMID- 21010258 TI - Tribromethyl alcohol (avertin, bromethol), 1928-1945. PMID- 21010259 TI - The eradication of tuberculosis in cattle; disease in relation to animal husbandry. PMID- 21010260 TI - [Not Available]. PMID- 21010261 TI - [Not Available]. PMID- 21010262 TI - [Not Available]. PMID- 21010263 TI - Benign lymphogranuloma of Schaumann with apparent involvement of the anteri pituitary. PMID- 21010264 TI - Reticulosis? PMID- 21010265 TI - Multiple chronic ulcers of the upper trunk in a young woman; acne conglobata. PMID- 21010266 TI - Epidermolysis bullosa. PMID- 21010267 TI - Lupus vulgaris treated with calciferol. PMID- 21010268 TI - Lupus vulgaris verrucosus of the buttocks. PMID- 21010269 TI - Lupus vulgaris with miliary lymphatic spread; epithelioma. PMID- 21010270 TI - Dermatomyositis. PMID- 21010271 TI - Keratoderma punctata. PMID- 21010272 TI - Oral use of penicillin in treatment of experimental Erysipelothrix rhusiopathiae infection in mice. PMID- 21010273 TI - Preparation of human typing sera by iso-immuninization of human donors with group specific substances. PMID- 21010274 TI - Relationship of turbidity to acid production by Lactobacillus arabinosus. PMID- 21010275 TI - Changes in erythrocytes of hamsters following castration, splenectomy, and subsequent liver, iron and testosterone injections. PMID- 21010276 TI - Sparing action of protein on the pantothenic acid requirement of the rat. PMID- 21010277 TI - Effect of atabrine on Tetrahymena geleii (Protozoa, Ciliata). PMID- 21010278 TI - Therapeutic effect of streptomycin in experimental murine pertussis. PMID- 21010279 TI - Electri control of polar growth in roots of Allium cepa. PMID- 21010280 TI - Effect of induce pain on pain threshold. PMID- 21010281 TI - Effect of adrenocorticotropic hormone (ACTH) on hypophysectomized adrenal demedullated rats. PMID- 21010282 TI - Hypertension produced in dogs by unilateral ligation of periadrenal blood vessels and tissue. PMID- 21010283 TI - The production of shock in rats by the drum method. PMID- 21010284 TI - Failure of homozygous embryo skin to prevent growth of autogenous tumor-grafts in the rat. PMID- 21010285 TI - Shock produced by the application of tourniquets to the hind limbs of rats. PMID- 21010286 TI - Inactivation of estrone by liver; assay method in vivo for dietary hepatic injury in rats. PMID- 21010287 TI - Studies on toxicity complement-fixing and immunogenic activity of typhus-infected yolk sacs. PMID- 21010288 TI - Synergistic action of nicotinamide upon penicillin. PMID- 21010289 TI - Studies on the action of penicillin; development of penicilli resistance by gonococcus. PMID- 21010290 TI - Studies on action of penicillin; virulence of penicillin resistant strains of meningococcus. PMID- 21010291 TI - Antibody response of swine to vaccination with formolized swine influenza virus adsorbed on alum. PMID- 21010292 TI - Inhibition of Salmonella cultures by streptomycin. PMID- 21010293 TI - Cytotoxicity of streptomycin and streptothricin. PMID- 21010294 TI - Physiological observations upon larval Eustrongylides; influence of oxygen lack upon survival and glycogen consumption. PMID- 21010295 TI - Effect of acute A-V fistula on circulation time and auricular pressure in dogs. PMID- 21010296 TI - Value of sunflower seed protein. PMID- 21010297 TI - Thermostable thromboplastin from human placenta and chicken brain. PMID- 21010298 TI - An improved cage for nitrogen studies with mice. PMID- 21010299 TI - Autoantibodies in rheumatic fever. PMID- 21010300 TI - Recuperation from the effects of tenotomy on neuromuscular transmission. PMID- 21010301 TI - Effect of neostigmine (prostigmin) and physostigmine upon the denervated iris of the cat. PMID- 21010302 TI - Effect of intermittent exposure to simulated high altitude in erythropoiesis in the guinea pig. PMID- 21010303 TI - Failure of intestinal extracts to prevent chick gizzard erosions. PMID- 21010304 TI - Carbon tetrachloride injury of the liver; the protective action of certain compounds. PMID- 21010305 TI - Blood pressure changes during electronarcosis. PMID- 21010306 TI - Fungistatic action of hair fat on Microsporon audouini. PMID- 21010307 TI - Effect of adrenalectomy on pigmentation of hair in rats fed a deficient diet. PMID- 21010308 TI - [Not Available]. PMID- 21010309 TI - [Not Available]. PMID- 21010310 TI - [Not Available]. PMID- 21010312 TI - [Not Available]. PMID- 21010311 TI - [Not Available]. PMID- 21010313 TI - [Not Available]. PMID- 21010314 TI - A study of edema following brain concussion. PMID- 21010315 TI - [Not Available]. PMID- 21010316 TI - [Not Available]. PMID- 21010317 TI - [Not Available]. PMID- 21010319 TI - [Not Available]. PMID- 21010318 TI - [Not Available]. PMID- 21010320 TI - [Not Available]. PMID- 21010321 TI - [Not Available]. PMID- 21010322 TI - [Not Available]. PMID- 21010323 TI - [Not Available]. PMID- 21010324 TI - [Not Available]. PMID- 21010325 TI - [Not Available]. PMID- 21010326 TI - [Not Available]. PMID- 21010327 TI - [Not Available]. PMID- 21010328 TI - [Not Available]. PMID- 21010329 TI - [Not Available]. PMID- 21010330 TI - [Not Available]. PMID- 21010331 TI - [Not Available]. PMID- 21010332 TI - [Not Available]. PMID- 21010333 TI - [Not Available]. PMID- 21010334 TI - [Not Available]. PMID- 21010335 TI - [Not Available]. PMID- 21010336 TI - [Not Available]. PMID- 21010337 TI - [Not Available]. PMID- 21010338 TI - [Not Available]. PMID- 21010339 TI - [Not Available]. PMID- 21010340 TI - [Not Available]. PMID- 21010341 TI - [Not Available]. PMID- 21010343 TI - [Not Available]. PMID- 21010342 TI - [Not Available]. PMID- 21010344 TI - [Not Available]. PMID- 21010345 TI - [Not Available]. PMID- 21010346 TI - [Not Available]. PMID- 21010347 TI - [Not Available]. PMID- 21010348 TI - [Not Available]. PMID- 21010349 TI - [Not Available]. PMID- 21010350 TI - [Not Available]. PMID- 21010351 TI - [Not Available]. PMID- 21010352 TI - [Not Available]. PMID- 21010353 TI - [Not Available]. PMID- 21010354 TI - [Not Available]. PMID- 21010355 TI - [Not Available]. PMID- 21010356 TI - [Not Available]. PMID- 21010357 TI - [Not Available]. PMID- 21010358 TI - [Not Available]. PMID- 21010359 TI - [Not Available]. PMID- 21010360 TI - [Not Available]. PMID- 21010361 TI - [Not Available]. PMID- 21010362 TI - [Not Available]. PMID- 21010363 TI - [Not Available]. PMID- 21010364 TI - [Not Available]. PMID- 21010365 TI - [Not Available]. PMID- 21010366 TI - [Not Available]. PMID- 21010367 TI - [Not Available]. PMID- 21010369 TI - [Not Available]. PMID- 21010368 TI - [Not Available]. PMID- 21010370 TI - [Not Available]. PMID- 21010371 TI - [Not Available]. PMID- 21010372 TI - Some practical aspects of the sterility problem in the female. PMID- 21010373 TI - Uterotubography in sterility. PMID- 21010374 TI - Head injuries. PMID- 21010375 TI - Infection in clean surgical wounds. PMID- 21010376 TI - The incidence of rheumatic heart disease in the Rocky Mountain region. PMID- 21010377 TI - Topical use of a combination of penicillin and sulfadiazine in a water soluble base for the treatment of sinusitis. PMID- 21010379 TI - [Not Available]. PMID- 21010378 TI - Foreign body in the uterus. PMID- 21010380 TI - [Not Available]. PMID- 21010381 TI - [Not Available]. PMID- 21010382 TI - [Not Available]. PMID- 21010383 TI - [Not Available]. PMID- 21010384 TI - [Not Available]. PMID- 21010385 TI - [Not Available]. PMID- 21010386 TI - [Not Available]. PMID- 21010387 TI - [Not Available]. PMID- 21010388 TI - [Not Available]. PMID- 21010389 TI - [Not Available]. PMID- 21010390 TI - [Not Available]. PMID- 21010391 TI - [Not Available]. PMID- 21010392 TI - [Not Available]. PMID- 21010393 TI - [Not Available]. PMID- 21010395 TI - [Not Available]. PMID- 21010394 TI - [Not Available]. PMID- 21010396 TI - [Not Available]. PMID- 21010397 TI - [Not Available]. PMID- 21010398 TI - [Not Available]. PMID- 21010399 TI - [Not Available]. PMID- 21010400 TI - [Not Available]. PMID- 21010401 TI - [Not Available]. PMID- 21010402 TI - [Not Available]. PMID- 21010403 TI - [Not Available]. PMID- 21010404 TI - [Not Available]. PMID- 21010405 TI - [Not Available]. PMID- 21010406 TI - [Not Available]. PMID- 21010407 TI - [Not Available]. PMID- 21010408 TI - [Not Available]. PMID- 21010409 TI - [Not Available]. PMID- 21010410 TI - [Not Available]. PMID- 21010411 TI - [Not Available]. PMID- 21010412 TI - [Not Available]. PMID- 21010413 TI - [Not Available]. PMID- 21010414 TI - [Not Available]. PMID- 21010415 TI - [Not Available]. PMID- 21010416 TI - [Not Available]. PMID- 21010417 TI - [Not Available]. PMID- 21010418 TI - [Not Available]. PMID- 21010419 TI - [Not Available]. PMID- 21010420 TI - [Not Available]. PMID- 21010421 TI - [Not Available]. PMID- 21010423 TI - [Not Available]. PMID- 21010422 TI - [Not Available]. PMID- 21010424 TI - [Not Available]. PMID- 21010425 TI - [Not Available]. PMID- 21010426 TI - [Not Available]. PMID- 21010427 TI - [Not Available]. PMID- 21010428 TI - [Not Available]. PMID- 21010429 TI - [Not Available]. PMID- 21010430 TI - [Not Available]. PMID- 21010431 TI - [Not Available]. PMID- 21010433 TI - [Not Available]. PMID- 21010432 TI - [Not Available]. PMID- 21010434 TI - [Not Available]. PMID- 21010435 TI - [Not Available]. PMID- 21010436 TI - [Not Available]. PMID- 21010437 TI - [Not Available]. PMID- 21010438 TI - [Not Available]. PMID- 21010439 TI - [Not Available]. PMID- 21010440 TI - [Not Available]. PMID- 21010442 TI - [Not Available]. PMID- 21010441 TI - [Not Available]. PMID- 21010443 TI - [Not Available]. PMID- 21010444 TI - [Not Available]. PMID- 21010445 TI - [Not Available]. PMID- 21010446 TI - [Not Available]. PMID- 21010448 TI - [Not Available]. PMID- 21010447 TI - [Not Available]. PMID- 21010449 TI - [Not Available]. PMID- 21010451 TI - [Not Available]. PMID- 21010450 TI - [Not Available]. PMID- 21010452 TI - [Not Available]. PMID- 21010453 TI - [Not Available]. PMID- 21010454 TI - [Not Available]. PMID- 21010455 TI - [Not Available]. PMID- 21010456 TI - [Not Available]. PMID- 21010457 TI - [Not Available]. PMID- 21010458 TI - [Not Available]. PMID- 21010459 TI - [Not Available]. PMID- 21010460 TI - [Not Available]. PMID- 21010461 TI - [Not Available]. PMID- 21010462 TI - [Not Available]. PMID- 21010463 TI - [Not Available]. PMID- 21010464 TI - The changing use of hospitals by the medical profession. PMID- 21010465 TI - Demobilization of the Medical Department. PMID- 21010466 TI - The general practitioner and rural medical care. PMID- 21010467 TI - Relationship of State and local health services in the whole program of public health. PMID- 21010468 TI - The nutritional state of the civilian population of Stuttgart Germany. PMID- 21010469 TI - A clinical study on the use of a protein supplement in treating persons with nutritive failure. PMID- 21010470 TI - Posttraumatic sarcoid-like lesions. PMID- 21010471 TI - The use of the Berman locator in removal of intra-ocular foreign bodies. PMID- 21010472 TI - Recent significant trends in the care of cerebral palsy. PMID- 21010473 TI - Tumors of the lung. PMID- 21010474 TI - Some practical aspects of the chemistry and pharmacology of local anesthetic drugs. PMID- 21010475 TI - Choice of anesthetic in urological surgery. PMID- 21010476 TI - Experience with rectal pentothal sodium in obstetrics. PMID- 21010477 TI - The two-hour pregnancy test. PMID- 21010478 TI - The genito-urinary symptoms of anorectal disease. PMID- 21010479 TI - Pediatric trends. PMID- 21010481 TI - The etiology and treatment of peptic ulcer; a review of the literature. PMID- 21010480 TI - Industrial medicine in the new era. PMID- 21010482 TI - Treatment of acute staphylococcic osteomyelitis with penicillin and without surgical operation. PMID- 21010483 TI - Penicillin in early syphilis. PMID- 21010484 TI - The importance of diaphragmatic hernia in the differential diagnosis of coronary artery disease. PMID- 21010485 TI - Gallstone obstruction of the intestine. PMID- 21010486 TI - Postoperative suprapubic hernia. PMID- 21010487 TI - DDT insecticide. PMID- 21010488 TI - Child hygiene among the American Indians; a chapter in early American pediatrics. PMID- 21010489 TI - Nutritional requirements of Drosophila hydei. PMID- 21010490 TI - Renal damage from ferroheme pigments myoglobin, hemoglobin, hematin. PMID- 21010491 TI - Reticulo-endothelial immune serum (REIS); experimental production of anemia and bartonellosis in rats by inhibitory dosage. PMID- 21010492 TI - Hookworm disease in Texas. PMID- 21010493 TI - The nature and action of the antibiotics. PMID- 21010494 TI - [Not Available]. PMID- 21010495 TI - [Not Available]. PMID- 21010496 TI - [Not Available]. PMID- 21010497 TI - [Not Available]. PMID- 21010498 TI - [Not Available]. PMID- 21010499 TI - [Not Available]. PMID- 21010501 TI - [Not Available]. PMID- 21010500 TI - [Not Available]. PMID- 21010502 TI - [Not Available]. PMID- 21010503 TI - [Not Available]. PMID- 21010504 TI - [Not Available]. PMID- 21010505 TI - [Not Available]. PMID- 21010507 TI - [Not Available]. PMID- 21010506 TI - [Not Available]. PMID- 21010508 TI - [Not Available]. PMID- 21010509 TI - [Not Available]. PMID- 21010510 TI - Electrophoretic analysis of serum in pregnancy and in pregnancy toxemia. PMID- 21010511 TI - Some observations on the technique of thyroidectomy. PMID- 21010512 TI - Individual variations in goitrous toxicity. PMID- 21010513 TI - On the intravital colour of the macula. PMID- 21010514 TI - Solid blast personnel injury; a clinical study. PMID- 21010515 TI - What is happening to Britain's wounded now? PMID- 21010516 TI - The diagnosis of migraine in flying personnel. PMID- 21010517 TI - A review of 18 cases of arthrotomy of knee joints. PMID- 21010518 TI - Local prophylaxis for gonorrhea; an improved technic. PMID- 21010519 TI - Rheumatic fever like syndrome caused by microaerophilic streptococcus with favorable results on penicillin therapy; report of case. PMID- 21010520 TI - Ladder splint with regulation litter for broken back. PMID- 21010521 TI - Fractures in electroshock therapy as related to roentgenographic spinal findings. PMID- 21010522 TI - Hyperextension back brace for treatment of compression fractures of the Vertebrae. PMID- 21010523 TI - Significance of salt (NcCl) in torrid temperatures. PMID- 21010524 TI - The effect of procaine on the inhibitory factory of penicillin. PMID- 21010525 TI - Suggestions in eye education. PMID- 21010527 TI - REPORT of Civilian Consultants Committee on Army amputation services. PMID- 21010526 TI - Methods for the determination of pH and salinity as field tests in the control of anopheline mosquitoes. PMID- 21010528 TI - Plant breeding and genetics to-day. PMID- 21010529 TI - Recent developments in science legislation. PMID- 21010530 TI - The future of entomology. PMID- 21010531 TI - Certain aspects of reproduction in a herd of silver foxes. PMID- 21010532 TI - Human heredity in relation to animal genetics. PMID- 21010534 TI - Dominance and heterosis. PMID- 21010533 TI - Linkage relations of flexed-tail in Peromyscus. PMID- 21010535 TI - Dried milk powder; factors affecting the sorption of carbon dioxide. PMID- 21010536 TI - Dried milk powder; the effect of light on keeping quality. PMID- 21010537 TI - Separation of starch and gluten; a rapid method of separation from wheat flour. PMID- 21010538 TI - Use of radon for industrial radiography. PMID- 21010539 TI - Golden jubilee of the discovery of x-rays. PMID- 21010540 TI - Colorimetric estimation of iron with resacetophenone-oxime. PMID- 21010541 TI - Some analogues of D.D.T. PMID- 21010542 TI - A note on the essential oil from ginger scrapings. PMID- 21010543 TI - Chemotherapy of some organo-mercury compounds; their activity against Staphylococcus aureus. PMID- 21010544 TI - An instance of grapes-poisoning. PMID- 21010545 TI - Role of manganese in the formation of vitamin C and carotene in plants. PMID- 21010546 TI - Studies in the synthesis of some substituted benzenesulphonamides; a simple new method of synthesis of some N-substituted azobenzene 4,4'-disulphonamides. PMID- 21010547 TI - Ether acetic as a fumigant. PMID- 21010548 TI - Racial significance of patellar groove. PMID- 21010549 TI - Symbiosis in spittle insect Ptyelus nebulosus Fabr. PMID- 21010550 TI - Palaeolithic sites in the Nellore District. PMID- 21010551 TI - D.D.T. and cattle ticks. PMID- 21010552 TI - Cultivation and systematic study of the tung oil yielding trees in India. PMID- 21010553 TI - Manufacture of yeast in India; some scientific problems. PMID- 21010554 TI - MANUFACTURE of glandular products. PMID- 21010555 TI - Pectin from Indian plant materials. PMID- 21010556 TI - Mixed bloods of the upper Monongahela Valley, West Virginia. PMID- 21010557 TI - Studies in the biology of the leech IX; the gross nervous system. PMID- 21010558 TI - On the structure and mechanics of the protozoan flagellum. PMID- 21010559 TI - A national Science Foundation; will it be a practical reality or a perpetual controversy? PMID- 21010560 TI - Protein apoferritin and ferritin in iron feeding and absorption. PMID- 21010561 TI - The use of synthetic L. casei factor in the treatment of sprue. PMID- 21010562 TI - A culture method for certain marine algae. PMID- 21010563 TI - Animpurity in some commercial penicillin preparations which interferes with the diazo reaction in determining blood phenols. PMID- 21010564 TI - A method of growing dense cultures of Paramecium. PMID- 21010565 TI - Convulsive effects of antibiotic agents on the cerebral cortex. PMID- 21010566 TI - Asearch for linkage between the A,B,C agglutinogens and phenylketonuria. PMID- 21010567 TI - A clinico-genetical study of mental defect. PMID- 21010568 TI - The causation of mongolism and its prognosis. PMID- 21010569 TI - Mongolism; a selective review. PMID- 21010570 TI - Presenting mental deficiency to students. PMID- 21010571 TI - The learning of low grade aments. PMID- 21010572 TI - Comparison of 500 complete and abbreviated revised Stanford scales administered to mental defectives. PMID- 21010573 TI - Influence of environment and etiology on social competence. PMID- 21010574 TI - Test patterns of defective delinquents on the Wechsler-Bellevue test. PMID- 21010575 TI - Test patterns of adjusted defectives on the Wechsler-Bellevue test. PMID- 21010576 TI - The benefits of good nursing supervision in institutions for mental defectives. PMID- 21010578 TI - Birthright, Inc.; its roots, fruits, and objectives. PMID- 21010577 TI - A program for low ability children in the regular grade; with special reference to the reading problem. PMID- 21010579 TI - Rhode Island's experiment in registration. PMID- 21010580 TI - Social control of mental defectives as a mental health measure. PMID- 21010581 TI - A note on eugenic prognosis in mental deficiency. PMID- 21010582 TI - The paternal factor in mongolism. PMID- 21010583 TI - Some I.Q. changes on the Stanford-Binet, Form L. PMID- 21010584 TI - Transient disturbances following gunshot wounds of the head. PMID- 21010585 TI - A study of pupillary inequalities in man. PMID- 21010586 TI - The adipose tissue of peripheral nerves. PMID- 21010587 TI - Abnormal suppression of cortical frequencies. PMID- 21010588 TI - Spinal tracts subserving micturition in a case of Erb's spinal paralysis. PMID- 21010589 TI - Practical approach to the war neuroses. PMID- 21010590 TI - Studies of German youth. PMID- 21010591 TI - Abnormal and subnormal rigidity. PMID- 21010592 TI - On the dynamic structure of concert-programs. PMID- 21010593 TI - A measurement of mother-child interaction. PMID- 21010594 TI - Environment and the draw-a-man test; the performance of Indian children. PMID- 21010595 TI - A new method for studying disorders of conceptual thinking. PMID- 21010596 TI - A comparison of psychiatric ratings with Minnesota multiphasic personality inventory scores. PMID- 21010597 TI - A followup study of neuropsychiatric screening. PMID- 21010598 TI - Security and breast-feeding. PMID- 21010599 TI - An additional study of food aversions. PMID- 21010600 TI - On re-innervation of paretic muscles by the use of their residual nerve supply. PMID- 21010601 TI - The effects of local applications of acetylcholine to the acoustic cortex. PMID- 21010602 TI - Cortical cerebellar atrophy without ataxia; primary circumscribed variety. PMID- 21010603 TI - Angiomatous malformation of the sylvian aqueduct with remarks on management of aqueductal obstructions. PMID- 21010604 TI - Terminal degeneration within the central nervous system as studied by a new silver method. PMID- 21010605 TI - Effect of extirpation of parastriate cortex on learned visual discriminations in monkeys. PMID- 21010606 TI - Neurinoma of the twelfth nerve. PMID- 21010607 TI - The pyramidal tract; the representation of the lateral corticospinal component in the spinal cord of the cat. PMID- 21010609 TI - The returned soldier; a challenge. PMID- 21010608 TI - Olivopontocerebellar atrophy in a cat. PMID- 21010610 TI - Social contacts of psychiatric patients; some preliminary observations. PMID- 21010611 TI - Review of legislation of the year 1945. PMID- 21010612 TI - Report on types and uses of locks in mental institutions. PMID- 21010613 TI - [Not Available]. PMID- 21010614 TI - [Not Available]. PMID- 21010615 TI - [Not Available]. PMID- 21010616 TI - [Not Available]. PMID- 21010617 TI - [Not Available]. PMID- 21010618 TI - Thoracoplasty. PMID- 21010619 TI - Thoracoplasty nursing care. PMID- 21010620 TI - A thoracoplasty from a patient's point of view. PMID- 21010621 TI - The scope and challenge of tuberculosis nursing. PMID- 21010622 TI - Fluorographic surveys and prevention of tuberculosis in Saskatchewan. PMID- 21010623 TI - The professional status of nursing. PMID- 21010624 TI - The relationship of public health nurses and social workers in the field. PMID- 21010625 TI - Fracture-dislocations of the cervical spine with paraplegia. PMID- 21010626 TI - The hands of the nurse. PMID- 21010627 TI - Diseases of the thyroid gland. PMID- 21010628 TI - Rare diseases of returning service men; beri-beri. PMID- 21010629 TI - Phosphorus burns and gastric perforation treated with sulphathiazole and penicillin. PMID- 21010630 TI - Individual and community health. PMID- 21010631 TI - The role of the nurse in speech correction. PMID- 21010632 TI - Feeding workers is an art. PMID- 21010633 TI - Fenestration for hearing impairment. PMID- 21010634 TI - A clinical trial of a synthetic mydriatic (dimethylaminoethyl benzilate ethochloride). PMID- 21010635 TI - A new synthetic mydriatic. PMID- 21010636 TI - Ocular findings in tropical typhus (Tsutsugamushi or Japanese river fever). PMID- 21010637 TI - Types, paper and printing in relation to eyestrain. PMID- 21010638 TI - Ophthalmic treatment in the field, 1943. PMID- 21010639 TI - Cavernous haemangioma of the orbit successfully removed by Shugrue's operation. PMID- 21010640 TI - An analysis and follow-up of 301 cases of battle casualty injury to the eyes. PMID- 21010641 TI - [Not Available]. PMID- 21010642 TI - [Not Available]. PMID- 21010644 TI - [Not Available]. PMID- 21010643 TI - [Not Available]. PMID- 21010645 TI - [Not Available]. PMID- 21010646 TI - [Not Available]. PMID- 21010647 TI - [Not Available]. PMID- 21010648 TI - [Not Available]. PMID- 21010649 TI - [Not Available]. PMID- 21010650 TI - [Not Available]. PMID- 21010651 TI - [Not Available]. PMID- 21010652 TI - [Not Available]. PMID- 21010653 TI - [Not Available]. PMID- 21010654 TI - Ophthalmic prisms, corrective and metric. PMID- 21010655 TI - Residual astigmatism with contact lenses. PMID- 21010656 TI - Effects of reconversion on employment of the blind. PMID- 21010657 TI - A review of tuberculosis in the field of otolaryngology for late 1944 and early 1945. PMID- 21010658 TI - War injuries to the auditory apparatus; clinical and audiometric observations. PMID- 21010659 TI - Mediastinal and subcutaneous emphysema of foreign body origin. PMID- 21010660 TI - Malarial pigment; a consideration of the mechanism of elimination from the duck. PMID- 21010661 TI - Malaria transmitted by bank blood transfusion; report of two cases. PMID- 21010662 TI - An improved method of examination of feces for the diagnosis of intestinal schistosomiasis. PMID- 21010663 TI - Canine histoplasmosis; a pathologic study of the three reported cases and the first case found in the Canal Zone. PMID- 21010664 TI - Acute infectious lymphocytosis. PMID- 21010665 TI - Specific types of alpha streptococcal antigen in unpotable water and water supplies. PMID- 21010666 TI - Relationship of the so-called giant-cell tumor to the frontal bone; report of a case. PMID- 21010667 TI - Liver abscess due to Friedlander's bacillus (K. pneumoniae) complicating adenocarcinoma of ampulla of Vater. PMID- 21010668 TI - POSTWAR education in pathology; first report by the Committee on Postwar Education, American Society of Clinical Pathologists. PMID- 21010669 TI - The correlation of the rapid slide method with the tube method for differentiating coagulase-positive from coagulase-negative strains of staphylococci. PMID- 21010670 TI - The photoelectric determination of erythrocyte count; basic principles and technic. PMID- 21010672 TI - Fite's fuchsin-formaldehyde method for acid-fast bacilli applied to frozen sections. PMID- 21010671 TI - Relative value of concentration methods of sputum and gastric contents for the detection of acid fast bacilli. PMID- 21010674 TI - Modifications of Macola's technic for Rowntree and Geraghty's functional test. PMID- 21010673 TI - Kolmer-like antigen prepared from lamb muscle. PMID- 21010675 TI - A simplified agitating apparatus for digestion of muscle in recovery of trichinae. PMID- 21010676 TI - The hemoglobin pipet as a source of error in photoelectric hemoglobinometry. PMID- 21010677 TI - Modified Westergren sedimentation test technic. PMID- 21010678 TI - Automatic trichrome stains. PMID- 21010679 TI - Repeated use of vacuum apparatus for obtaining blood specimens. PMID- 21010680 TI - [Not Available]. PMID- 21010681 TI - [Not Available]. PMID- 21010682 TI - [Not Available]. PMID- 21010683 TI - [Not Available]. PMID- 21010685 TI - [Not Available]. PMID- 21010684 TI - [Not Available]. PMID- 21010686 TI - [Not Available]. PMID- 21010687 TI - [Not Available]. PMID- 21010688 TI - [Not Available]. PMID- 21010689 TI - [Not Available]. PMID- 21010690 TI - [Not Available]. PMID- 21010691 TI - [Not Available]. PMID- 21010692 TI - [Not Available]. PMID- 21010693 TI - [Not Available]. PMID- 21010694 TI - [Not Available]. PMID- 21010695 TI - [Not Available]. PMID- 21010696 TI - [Not Available]. PMID- 21010697 TI - [Not Available]. PMID- 21010698 TI - [Not Available]. PMID- 21010699 TI - Cirrhosis of the liver and of the pancreas and disturbances of the sugar metabolism in an eight-week-old infant. PMID- 21010700 TI - A new type of breast pump. PMID- 21010701 TI - [Not Available]. PMID- 21010702 TI - Reactions to intradermal administration of scarlet fever streptococcus toxin in rheumatic cardiac children. PMID- 21010703 TI - Children's idiosyncrasies. PMID- 21010704 TI - The portal of entry of poliomyelitis. PMID- 21010705 TI - Acute poliomyelitis; massive atelectasis. PMID- 21010706 TI - Tetanus; recovery. PMID- 21010707 TI - Activity group therapy for the exceptional child. PMID- 21010708 TI - SCHOOL health policies for the handicapped. PMID- 21010709 TI - Improving the relationship between the community and the class for mentally retarded. PMID- 21010710 TI - [Not Available]. PMID- 21010711 TI - [Not Available]. PMID- 21010712 TI - [Not Available]. PMID- 21010713 TI - [Not Available]. PMID- 21010714 TI - [Not Available]. PMID- 21010715 TI - [Not Available]. PMID- 21010716 TI - [Not Available]. PMID- 21010717 TI - [Not Available]. PMID- 21010718 TI - [Not Available]. PMID- 21010719 TI - [Not Available]. PMID- 21010720 TI - [Not Available]. PMID- 21010721 TI - [Not Available]. PMID- 21010722 TI - [Not Available]. PMID- 21010723 TI - [Not Available]. PMID- 21010724 TI - [Not Available]. PMID- 21010725 TI - [Not Available]. PMID- 21010726 TI - [Not Available]. PMID- 21010727 TI - [Not Available]. PMID- 21010728 TI - [Not Available]. PMID- 21010729 TI - [Not Available]. PMID- 21010730 TI - [Not Available]. PMID- 21010731 TI - Is pharmacy a trade or a profession? PMID- 21010732 TI - Quantitative determination of demerol and its separation from opium alkaloids. PMID- 21010733 TI - Recent advances in drug therapy. PMID- 21010734 TI - Regarding the processing of calcium chloride from the technical product. PMID- 21010735 TI - The excretion of sodium trichloracetate. PMID- 21010737 TI - The absorption of cinchona alkaloids in the chick and its relationship to antimalarial activity. PMID- 21010736 TI - The by-effects of anti-hemorrhagic quinones; antipressor action in chronic hypertension in man. PMID- 21010738 TI - Goitrogenic agents and thyroidal iodine; their pharmacodynamic interplay upon thyroid function. PMID- 21010739 TI - A contribution to the pharmacology of 5-nitro-2-furaldehyde semicarbazone. PMID- 21010740 TI - Reaction of tissue aldehydes with certain drugs. PMID- 21010741 TI - Induction of nutritional deficiency by oral administration of streptomycin. PMID- 21010742 TI - The choleretic action of dehydrocholic acid (decholin) and deoxycholic acid (degalol) in chronic biliary fistula dogs. PMID- 21010743 TI - A note on the Bell and Krantz modification of the Knudson-Dresbach chemical assay of digitalis. PMID- 21010744 TI - The response of the hamster to drugs. PMID- 21010745 TI - Studies on factors influencing the toxicity of nicotine; the effects of water and food deprivation; disturbed liver function and rate of administration. PMID- 21010746 TI - Determination of DDT (2,2-bis (p-chlorophenyl) 1,1,1-trichloroethane) and its metabolite in biological materials by use of the Schechter-Haller method. PMID- 21010747 TI - [Not Available]. PMID- 21010748 TI - [Not Available]. PMID- 21010749 TI - [Not Available]. PMID- 21010751 TI - The future of German pharmaceutical industry. PMID- 21010750 TI - [Not Available]. PMID- 21010752 TI - POSSIBILITIES of biological warfare. PMID- 21010753 TI - Snake venom as a therapeutic agent. PMID- 21010754 TI - Purification and properties of desoxyribonuclease isolated from beef pancreas. PMID- 21010755 TI - Isolation of pure hexokinase from yeast. PMID- 21010756 TI - Isolation of crystalline hexokinase and other proteins from yeast. PMID- 21010757 TI - Crystalline soybean trypsin inhibitor. PMID- 21010758 TI - An improved method for the crystallization of trypsin. PMID- 21010759 TI - The effectiveness of the spectrum in chlorophyll formation. PMID- 21010760 TI - Some properties of protoplasmic gels. PMID- 21010761 TI - Studies on the nutritional basis of abnormal behavior in albino rats; the effect of pyridoxine deficiency upon sound-induced magnesium tetany. PMID- 21010762 TI - Studies of abnormal behavior in the rat; analysis of stomachs of rats repeatedly exposed to auditory stimulation. PMID- 21010763 TI - Responses of sheep in a discrimination problem with variations of the position of the signal. PMID- 21010764 TI - Discrimination generalization by macaque monkeys to unidimensional and multidimensional stimuli. PMID- 21010765 TI - The relation of previous experience to insightful problem-solving. PMID- 21010766 TI - Studies in the interrelations of central nervous structures in binocular vision; the lack of bilateral transfer of visual discriminative habits acquired monocularly by the pigeon. PMID- 21010767 TI - Studies in the interrelations of central nervous structures in binocular vision: the conditions under which interocular transfer of discriminative habits takes place in the pigeon. PMID- 21010768 TI - Procedures in training teachers to prevent and reduce mental hygiene problems. PMID- 21010769 TI - A study of the fears of rural children. PMID- 21010770 TI - Influence of parental attitudes on children's personal inventory scores. PMID- 21010771 TI - An analysis of children's maze learning, in terms of stages of learning. PMID- 21010772 TI - Note on Wellman's re-analysis of IQ changes of orphanage preschool children. PMID- 21010773 TI - Temporal change in perceptual space. PMID- 21010774 TI - Intellectual and personality traits of a group of triplets. PMID- 21010775 TI - Value of the Maller controlled association test as a screening device. PMID- 21010776 TI - Scoring samples for the Rosenzweig picture-frustration study. PMID- 21010777 TI - Sex differences in the projective doll play of preschool children. PMID- 21010778 TI - A rapid method of estimating the IQ's of subnormal white adults. PMID- 21010779 TI - The interrelationships of attitudes toward Russia and some general desires. PMID- 21010780 TI - Attitudes and cognitive organization. PMID- 21010781 TI - Measurement of hyper-associative activity during elation. PMID- 21010782 TI - A study of children' attitudes and the influence of a commercial motion picture. PMID- 21010783 TI - Changes from 1923 to 1943 in the attitudes of public school and university students. PMID- 21010784 TI - The factorial analysis of the electroencephalogram. PMID- 21010785 TI - Studies in occupational analysis levels of difficulty, responsibility, and importance in technical judgment and design operations in ordnance and mechanical engineering. PMID- 21010786 TI - Health of the industrial population. PMID- 21010787 TI - Problems of industrial health in India. PMID- 21010788 TI - Some observations during the 1943 havoc (in the District of Murshidabad). PMID- 21010789 TI - Isolation of the tuberculosis. PMID- 21010790 TI - HEALTH and physical fitness for all American children and youth. PMID- 21010791 TI - The American Academy of Physical Education. PMID- 21010792 TI - SUGGESTED school health policies. PMID- 21010793 TI - The tuberculin jelly patch test in infant welfare centres and in the school medical service; a preliminary report. PMID- 21010794 TI - The development of rural water supplies with special reference to the County of Lincoln, parts of Kesteven. PMID- 21010795 TI - Amoebic infection. PMID- 21010796 TI - The protection of child life. PMID- 21010797 TI - TEACHING of tuberculosis to medical students. PMID- 21010798 TI - The use of D.D.T. PMID- 21010799 TI - A note on ointment bases. PMID- 21010800 TI - An outbreak of streptococcal infection in a maternity home. PMID- 21010801 TI - A medical study of the effect of TNT on workers in a bomb and shell loading plant. PMID- 21010803 TI - Has public health any future? PMID- 21010802 TI - A fatal case of aplastic anemia preceded by toxic hepatitis following exposure to TNT. PMID- 21010804 TI - The fresh produce of fertile soil is the real basis of public health. PMID- 21010805 TI - The unparented child. PMID- 21010806 TI - An epidemic of a severe pneumonitis in the bayou region of Louisiana. PMID- 21010807 TI - Tularemia; attempted transmission by each of two species of fleas; Xenopsylla cheopis (Roths.) and Diamanus montanus (Baker). PMID- 21010808 TI - London's water supply; experiences in safeguarding its purity in war. PMID- 21010809 TI - Industry converts sewage works effluent into water supply. PMID- 21010810 TI - The disposal of industrial wastes. PMID- 21010811 TI - The effect of Cox-type vaccine on louse-borne typhus fever; an account of 61 cases of naturally occurring typhus fever in patients who had previously received one or more injections of Cox-type vaccine. PMID- 21010812 TI - The ineffectiveness of intensive mapharsen, bismuth and carbasone as curative drugs for chronic malaria. PMID- 21010813 TI - Pigmentation of the palate and subungual tissues associated with suppressive quinacrine hydrochloride therapy. PMID- 21010814 TI - Complement fixation in relapsing Plasmodium vivax malaria. PMID- 21010815 TI - Scrub-typhus. PMID- 21010816 TI - Observations on the incidence of Wuchereria bancrofti larvae in the native population of the Solomon Islands area. PMID- 21010817 TI - A concentration method for demonstrating microfilariae in blood. PMID- 21010818 TI - Portuguese man-of war stings; a case report. PMID- 21010819 TI - Anopheles punctimacula D. & K. as the vector of malaria in Medellin, Columbia, South America. PMID- 21010820 TI - Two exogenous cases of visceral leishmaniasis (kalaazar) in the United States with notes on cultivation of Leishmania donovani in vitro. PMID- 21010821 TI - Report on a case of balatidiasis. PMID- 21010822 TI - Fresh laboratory material for teaching medical parasitology. PMID- 21010823 TI - Lepromin skin tests in Boeck's sarcoid. PMID- 21010825 TI - Elephantiasis and septic infection. PMID- 21010824 TI - The reaction to lepromin of patients with sarcoid or tuberculosis compared with that of patients in general hospitals with a discussion of the mechanism of the reaction. PMID- 21010826 TI - On tropical eosinophilia associated with pulmonary signs (Loeffler's syndrome). PMID- 21010827 TI - Significant observations on amoebic hepatitis; a clinical review of 200 patients. PMID- 21010828 TI - Public health conditions in wartime; Northern Gold Goast. PMID- 21010829 TI - The effect of war on public health. PMID- 21010830 TI - The management of pure tuberculous and mixed infection empyemata. PMID- 21010831 TI - Chronic pleural empyema (its surgical treatment). PMID- 21010832 TI - Evaluation of various surgical procedures in the treatment of pulmonary tuberculosis. PMID- 21010833 TI - The treatment of tuberculous empyema. PMID- 21010834 TI - The treatment of tuberculous empyemas with tyrothricin. PMID- 21010835 TI - Tuberculous empyema treated with vitamin A-D concentrate; a preliminary report. PMID- 21010836 TI - CHEMOTHERAPY in tuberculosis. PMID- 21010837 TI - Penicillin therapy of early syphilis; follow-up examination of 792 patients six or more months after treatment. PMID- 21010838 TI - The treatment of gonorrhoea with penicillin. PMID- 21010839 TI - Gumma of the thyroid gland. PMID- 21010840 TI - Intensive arsenotherapy of early syphilis. PMID- 21010841 TI - Oral administration of bistovol in general paralysis. PMID- 21010842 TI - Syphilis in seventeenth century Lancashire. PMID- 21010843 TI - Genital oedema in relation to filariasis in the Gold Coast. PMID- 21010844 TI - The Malay chin. PMID- 21010845 TI - Creation, and the blessing or the curse upon fruitfulness; an anthropogeographical interpretation of Genesis I-III. PMID- 21010847 TI - Carrier organization and operation. PMID- 21010846 TI - The English; are they an older race? PMID- 21010848 TI - Pilots with repeated pilot-inaptitude accidents. PMID- 21010849 TI - A physiological study of aviators during combat flying. PMID- 21010850 TI - Acute otitic barotrauma resulting from low-pressure chamber tests. PMID- 21010851 TI - Airsickness during early flying training. PMID- 21010852 TI - Cardiovascular changes in motion sickness. PMID- 21010853 TI - A comparative study of the effects of exercise and anoxia upon the human electrocardiogram. PMID- 21010855 TI - Neuropsychiatry as an integral part of aviation medicine. PMID- 21010854 TI - The effects of mild anoxia on neuromuscular coordination in skilled investigators. PMID- 21010856 TI - Experiments on cell and axon orientation in vitro; the role of colloidal exudates in tissue organization. PMID- 21010857 TI - Natural heteroagglutinins in the serum of the spiny lobster, Penulirus interruptus; taxonomic range of activity, electrophoretic and immunizing properties. PMID- 21010858 TI - Normal and abnormal development of the eggs of Ciona. PMID- 21010859 TI - Thyroid and pituitary hormones in relation to regeneration; regeneration of the hind leg of the newt, Triturus viridescens, with different combinations of thyroid and pituitary hormones. PMID- 21010860 TI - The role of the sensory fibers in the differentiation of the spinal cord in sheep. PMID- 21010861 TI - Maintenance of normal structure in heteroploid salamander larvae, through compensation of changes in cell size by adjustment of cell number and cell shape. PMID- 21010862 TI - The structure and properties of the trichocysts of Paramecium. PMID- 21010863 TI - Effect of roentgen rays on bone growth in pigeons. PMID- 21010864 TI - The development of late gastrula explants of Rana pipiens in salt solution. PMID- 21010865 TI - Nuclear phenomena associated with secretion in certain gland cells with especial reference to the origin of cytoplasmic nucleic acid. PMID- 21010866 TI - Quantitative studies on the seasonal development of the deferent ducts in passerine birds. PMID- 21010867 TI - Factors affecting in vitro ovulation in the frog. PMID- 21010868 TI - A further study of oxidation-reduction pattern in teleost development. PMID- 21010869 TI - The problem of central nervous reorganization after nerve regeneration and muscle transposition. PMID- 21010870 TI - The social distribution of cancer of the scrotum and cancer of the penis. PMID- 21010871 TI - Calcium and potassium content of secretions from noncancerous and cancerous stomachs. PMID- 21010872 TI - Demonstration of an enzyme-inhibiting factor in the serum of cancer patients; a preliminary stury. PMID- 21010873 TI - The respective roles of longevity and genetic specificity in the occurrence of spontaneous tumors in the hybrids between two inbred lines of rats. PMID- 21010874 TI - The growth of mammalian tumors in fertile eggs; is a filterable cancer virus produced? PMID- 21010875 TI - The superior vena caval syndrome; report of thirty-five cases. PMID- 21010876 TI - A study of the prothrombin time in normal subjects and in patients with arteriosclerosis; a preliminary report. PMID- 21010877 TI - Normal electrocardiograms in cardiovascular disease. PMID- 21010878 TI - Certain effects of positive pressure respiration on the circulatory and respiratory systems. PMID- 21010879 TI - Bigeminy; an electrocardiographic study of bigeminal rhythms. PMID- 21010880 TI - Staphylococcus aureus septicemia and pericarditis treated with penicillin. PMID- 21010881 TI - Electrocardiographic changes resulting from phosphorus poisoning; report of a case. PMID- 21010882 TI - Congenital defect of the aortic vestibule complicated by bacterial endocarditis with perforation and death from cardiac tamponade; report of a case. PMID- 21010883 TI - The clinical significance of precordial leads in the diagnosis of heart disease; II. PMID- 21010884 TI - Fatt acid metabolism; ketone bodies as intermediates of acetate oxidation in animal tissues. PMID- 21010885 TI - A study of the effect of growth substrate on the respiration of Azotobacter. PMID- 21010886 TI - Inhibition of alkaline serum phosphatase activity during liver disease. PMID- 21010887 TI - Analytical determination and some properties of several thyroid-inhibiting compounds and of substance related to them. PMID- 21010888 TI - The effect of lecithinas on human serum globulins. PMID- 21010889 TI - The action of phenylmercuric nitrate; effects on enzyme systems. PMID- 21010890 TI - The action of phenylmercuric nitrate; sulfhydryl antagonism of respiratory depression caused by phenylmercuric nitrate. PMID- 21010891 TI - Fats of insects; composition of the fat of Melano-plus atlantis Riley. PMID- 21010892 TI - Fats of insects: Sphenarium purpurascens Charpentier. PMID- 21010893 TI - The nature of the antibacterial agent from Anemone pulsatilla. PMID- 21010894 TI - The amino acid requirements of Streptococcus faecalis and the use of this organism for the determination of threonine in natural products. PMID- 21010895 TI - Dietary factors in the regulation of liver lipid concentration. PMID- 21010896 TI - The effect of riboflavin analogues upon the utilization of riboflavin and flavin adenine dinucleotide by Lactobacillus casei. PMID- 21010897 TI - The fractionation and photometric estimation of the estrogens in human pregnancy urine. PMID- 21010898 TI - The influence of ingested choline upon choline-containing and non-choline containing phospholipids of the liver as measured by radioactive phosphorus. PMID- 21010899 TI - The distribution pattern of fatty acids in glycerides of milk fat. PMID- 21010900 TI - Storage of hendecanoic acid in the white rat. PMID- 21010901 TI - A modified method for the quantitative determination of the thymol turbidity reaction of serum. PMID- 21010902 TI - Studies on phosphatase-containing enzyme products for hydrolysis of cocarboxylase in brewers' type yeasts and wheat embryo at various hydrogen ion concentrations. PMID- 21010903 TI - Effect of inhibition of glycolysis and compounds related to glycolysis on acetylcholine synthesis. PMID- 21010904 TI - The effect of the preceding diet upon fasting ketonemia. PMID- 21010905 TI - Preparation of streptomycin. PMID- 21010906 TI - Some pyridyl analogues of triphenylmethane. PMID- 21010907 TI - Some derivatives of 3-aminoquinoline. PMID- 21010908 TI - The bromination of 4:4'-diamidino-alpha,omega-diphenoxypropane and of 4:4 diamidino-stilbene. PMID- 21010909 TI - Carbohydrate phosphoric esters; the alkaline hydrolysis of alpha methylglucopyranoside-6-phosphate, methylglucofuranoside-3-phosphates iso propylidene glucofuranose-3- and -6-phosphates. PMID- 21010910 TI - The enzymic synthesis and degradation of starch; the synthesis of amylopectin. PMID- 21010911 TI - The enzymic synthesis and degradation of starch; the amylolytic function of the Q enzyme of the potato. PMID- 21010912 TI - The mechanism of condensation of the anhydrides of mono- and di-substituted succinic acids with aromatic hydrocarbons under the conditions of the Friedel Crafts reaction. PMID- 21010913 TI - Sulphur derivatives of thiazoles. PMID- 21010914 TI - Note on the purification and resolution of dl-adrenaline. PMID- 21010915 TI - The synthesis of cardiazole (pentamethylenetetrazole) by the action of hydrazoic acid on cyclohexanone. PMID- 21010916 TI - The preparation of 2-amino-7-hydroxyfluorene. PMID- 21010917 TI - The behavior of sodium stearate with cetane and water. PMID- 21010918 TI - Improved methods of preparation of permselective collodion membranes combining extreme ionic selectivity with high permeability. PMID- 21010919 TI - The lamina dura in roentgenographic interpretation; changes during tooth movement. PMID- 21010920 TI - The periodontal membrane in function. PMID- 21010921 TI - Recording the Frankfort-mandibular-plane angle using oriented mandibular radiogram and sectioned oriented cast. PMID- 21010922 TI - Notes on diagnosis. PMID- 21010923 TI - Mixed tumors of the lip. PMID- 21010924 TI - Fifty years of oral roentgenography; forty years of personal experience in retrospect. PMID- 21010925 TI - Acceleration of the setting of zinc oxide cements. PMID- 21010926 TI - Acrylic tooth-making technique for denture purposes. PMID- 21010927 TI - Surgical extension of the buccal sulous of the mandible. PMID- 21010928 TI - Developmental cysts of the maxilla. PMID- 21010929 TI - The dental condition of West Indian recruits. PMID- 21010930 TI - Two unusual cases of salivary calculus. PMID- 21010931 TI - A rhinolith revealed by dental x-ray films. PMID- 21010932 TI - Rehabilitation of the mouth. PMID- 21010933 TI - Teeth and the school doctor. PMID- 21010934 TI - Anatomic characteristics important in radiodontic interpretation. PMID- 21010935 TI - MAKING prints of good quality; checking darkroom equipment. PMID- 21010936 TI - Diagnostic intra-oral radiographs. PMID- 21010937 TI - Preoperative and postoperative extraction technic. PMID- 21010938 TI - Ring-bar support for posterior acrylic resin pontics. PMID- 21010939 TI - Formation of the rugae. PMID- 21010941 TI - Management of atypical oral fistula. PMID- 21010940 TI - Emergency repair for full upper acrylic resin denture. PMID- 21010942 TI - Accidentally acquired cleft palate. PMID- 21010943 TI - Occlusion ranks first in denture construction. PMID- 21010944 TI - Improved gold-porcelain crown. PMID- 21010945 TI - Infected incisive canal cyst. PMID- 21010946 TI - Ionization or electrolytic medication in treatment of infected root canals. PMID- 21010947 TI - SHARP needles main factor in curbing injection discomfort. PMID- 21010948 TI - The rest position of the mandible and its significance to dental science. PMID- 21010949 TI - New observations on inhibitory and productive factors in dental caries. PMID- 21010950 TI - The biochemistry of oral calculus the presence of carbonic anhydrase in human saliva. PMID- 21010951 TI - The development of thermal control. PMID- 21010952 TI - Morphologic alteration of smalle oral treponemes during aging of cultures; effect of age on viability of spirochetal cultures. PMID- 21010953 TI - Gerodontology; the study of changes in oral tissues associated with aging. PMID- 21010954 TI - Hard tissue lesions of the mouth. PMID- 21010956 TI - The new concept of periodontoclasia. PMID- 21010955 TI - Anatomy of the face and mouth from the standpoint of the denture prosthetist. PMID- 21010957 TI - Nutrition and dental health; vitamin C. PMID- 21010958 TI - Methods of ridge preservation in full-denture construction. PMID- 21010959 TI - The importance of recognizing the beginning of malignant growth in the oral cavity. PMID- 21010960 TI - Will the business side of dentistry displace the professional side? PMID- 21010961 TI - Penicillin. PMID- 21010962 TI - The relation between partial dentures and the living tissues. PMID- 21010963 TI - The action of fluorine in limiting dental caries. PMID- 21010964 TI - Enamel hypoplasia. PMID- 21010965 TI - [Not Available]. PMID- 21010966 TI - [Not Available]. PMID- 21010967 TI - [Not Available]. PMID- 21010968 TI - [Not Available]. PMID- 21010969 TI - A new technique for performing quantitative contact (patch) skin tests. PMID- 21010970 TI - The simple puncture with a needle as an aid in the diagnosis of the hypochromic and achromic macules of leprosy. PMID- 21010971 TI - Studies in hypersensitivity to light; a preliminary report. PMID- 21010972 TI - So-called pustular psoriasis. PMID- 21010973 TI - Direct current combined with x-ray therapy; erythema studies; preliminary experiments. PMID- 21010975 TI - Filling the special diet prescription; high protein diets. PMID- 21010974 TI - Some clinical aspects of protein nutrition. PMID- 21010976 TI - Biological value of food yeast proteins and their role as supplements to the proteins of the cereal grains. PMID- 21010977 TI - Effect of large-scale methods of preparation on vitamin content of food; potatoes. PMID- 21010978 TI - Some factors influencing the food intake of preschool children. PMID- 21010979 TI - A further analysis of food selections of eighty families in Lubbock, Texas. PMID- 21010980 TI - Food service in an UNRRA camp in Egypt. PMID- 21010981 TI - Management of chronic constipation. PMID- 21010982 TI - Modern concept of congenital megacolon (Hirschsprung's disease). PMID- 21010983 TI - Some dermatologic aspects of allergy. PMID- 21010984 TI - Diverticula of the colon versus gallstones. PMID- 21010985 TI - Gastric carcinoma; review of errors in diagnosis. PMID- 21010986 TI - Clinical evaluation of the laboratory tests of the stomach. PMID- 21010987 TI - Heredity an important factor for the early diagnosis of gastro-intestinal cancer. PMID- 21010988 TI - Further observations on the value of the pregnandiol test for pregnancy. PMID- 21010989 TI - Testosterone propionate in treatment of senile pruritus. PMID- 21010990 TI - The reliability of the Aschheim-Zondek test in pregnancy; a report of two thousand routine tests. PMID- 21010991 TI - Thiouracil derivatives of greater activity for the treatment of hyperthyroidism. PMID- 21010992 TI - Some observations on the question of hypoparathyroidism of diencephalic origin. PMID- 21010993 TI - Opposing expert testimony. PMID- 21010994 TI - Rehabilitation center; psychiatry and group therapy. PMID- 21010995 TI - Types of chromosome structural change induced by the irradiation of Tradescantia microspores. PMID- 21010996 TI - The production of chromosome structural changes in Tradescantia microspores in relation to dosage, intensity and temperature. PMID- 21010997 TI - The genetics of corky; the New World alleles and their possible role as an interspecific isolating mechanism. PMID- 21010998 TI - Genetical and cytological studies of Musa; certain aspects of polyploidy. PMID- 21010999 TI - The crinkled dwarf allelomorph series in the New World cottons. PMID- 21011000 TI - Synmmetrical and asymmetrical reduction in Ascomycetes. PMID- 21011001 TI - Evidence on chromosome homology in the amphidiploid New World cottons. PMID- 21011002 TI - Carcinoma subsequent to the radiotherapeutic menopause. PMID- 21011003 TI - The value of physiologic substrates in sperm migration in selected cases of human infertility; observations on a series of 106 patients. PMID- 21011004 TI - Postmenopausal endome trium and its relation to adenocarcinoma of the corpus uteri; a study of 236 cases. PMID- 21011005 TI - The anovulatory cycle and menstruation. PMID- 21011006 TI - Selective treatment of antepartum hemorrhage. PMID- 21011007 TI - A histologic study of the effect of irradiation on adenocarcinoma of the endometrium. PMID- 21011008 TI - The management and treatment of the late toxemias of pregnancy. PMID- 21011009 TI - Oral therapy with ethinyl estradiol in the menopause. PMID- 21011010 TI - Pyridoxine failure in nausea and vomiting of pregnancy. PMID- 21011011 TI - Sulfathiazole in the control of epidemic diarrhea of the newborn. PMID- 21011012 TI - Sulfanilamide and sulfathiazole absorption via rectum and vagina; further studies. PMID- 21011013 TI - Are antihormones formed during pregnancy? PMID- 21011014 TI - Ethinyl estradiol in the treatment of metrorrhagia. PMID- 21011015 TI - Puerperal sterilization. PMID- 21011016 TI - Panhysterectomy without vaginal cleansing. PMID- 21011017 TI - Cesarean section on a poliomyelitic patient confined to a respirator. PMID- 21011018 TI - Double uterus and double vagina; identical doubles demonstrated by colpohysterosalpingography. PMID- 21011019 TI - The subperitoneal Baldy-Webster uterine suspension. PMID- 21011020 TI - Aplastic anemia simulating ectopic gestation; report of a case. PMID- 21011021 TI - Hydatidiform degeneration of placenta, complete with fetus. PMID- 21011022 TI - The relation of the theca-cells to disturbances of the menstrual cycle. PMID- 21011023 TI - Blood-pressure of relatives of patients with toxaemia of late pregnancy. PMID- 21011024 TI - The prevention of premature labour. PMID- 21011025 TI - Carcinoma corporis uteri in 2 sisters aged 34 and 32 years. PMID- 21011026 TI - Rupture of the rectus abdominis muscle during pregnancy. PMID- 21011028 TI - Notes on the treatment of vesicovaginal fistula. PMID- 21011027 TI - Myasthenia gravis and pregnancy. PMID- 21011029 TI - Treatment of the patient with syphilis. PMID- 21011030 TI - Thyroid insufficiency; some of the slight or minor manifestations. PMID- 21011031 TI - The treatment of a type of pruritus by drainage operation. PMID- 21011032 TI - Rectal reflexes and their relation to chronic diseases. PMID- 21011033 TI - ORAL therapy for pruritus ani. PMID- 21011034 TI - Pruritus ani comments. PMID- 21011035 TI - The librarian as a member of the nursing school faculty. PMID- 21011036 TI - Library therapy. PMID- 21011037 TI - The health program for schools of nursing. PMID- 21011038 TI - Serologic studies in typhus-vaccinated individuals; the effect of non-typhus fevers on the Weil-Felix and complement-fixing antibodies. PMID- 21011039 TI - The action of synthetic detergents upon certain strains of bacteriophage and virus. PMID- 21011040 TI - Studies on the mechanism of host resistance in experimental leptospirosis icterohemorrhagica. PMID- 21011041 TI - Factors influencing leukoagglutination by antileukocytic sera. PMID- 21011042 TI - Vesication and some vesicants. PMID- 21011043 TI - Control of hazards in the luminous dial painting industry. PMID- 21011044 TI - Methyl iodide poisoning. PMID- 21011045 TI - The solubility or distribution coefficient of carbon tetrachloride in water, whole blood, and plasma. PMID- 21011046 TI - The incidence of sepsis in industrial wounds. PMID- 21011047 TI - Ideal seeing conditions; the study of the human visual system as a basis for prescribing lighting. PMID- 21011048 TI - Silicious exposures in the fire brick industry; engineering study. PMID- 21011049 TI - Silicious exposures in the fire brick industry; roentgenologic study. PMID- 21011050 TI - Control of the lead poisoning hazard in can manufacturing; the bodymaking machine (side-seamer). PMID- 21011051 TI - Electric arc welding ventilation and its relation to oxygen deficiency. PMID- 21011052 TI - Filter paper spot sampling of air-borne solids. PMID- 21011053 TI - The effect of triethylene glycol vapor on airborne beta hemolytic streptococci in hospital wards; the action of glycol vapors at low relative humidities. PMID- 21011054 TI - Studies on nutrition and avian malaria; protein deficiency. PMID- 21011055 TI - Phase variation of Andrewes in a coliform bacterium. PMID- 21011057 TI - Experimental gonococcal infection of the rabbit's eye, method of production. PMID- 21011056 TI - The culturing of blood clots for Brucella organisms. PMID- 21011058 TI - Experimental gonococcal infection of the rabbit's eye; course of the disease and its pathology. PMID- 21011059 TI - Experimental gonococcal infection of the rabbit's eye; treatment with prophylactic and therapeutic agents. PMID- 21011060 TI - Immunological relationships of Plasmodium gallinaceum and Plasmodium lophurae. PMID- 21011061 TI - Susceptibility of vervet monkeys to poliomyelitis virus in flies collected at epidemics. PMID- 21011062 TI - Field experiment on an automatic siphon sluice in malaria control. PMID- 21011063 TI - [Not Available]. PMID- 21011064 TI - [Not Available]. PMID- 21011065 TI - [Not Available]. PMID- 21011066 TI - [Not Available]. PMID- 21011068 TI - [Not Available]. PMID- 21011067 TI - [Not Available]. PMID- 21011069 TI - [Not Available]. PMID- 21011070 TI - [Not Available]. PMID- 21011071 TI - [Not Available]. PMID- 21011072 TI - [Not Available]. PMID- 21011073 TI - [Not Available]. PMID- 21011074 TI - [Not Available]. PMID- 21011075 TI - [Not Available]. PMID- 21011076 TI - [Not Available]. PMID- 21011077 TI - [Not Available]. PMID- 21011078 TI - [Not Available]. PMID- 21011080 TI - [Not Available]. PMID- 21011079 TI - [Not Available]. PMID- 21011081 TI - [Not Available]. PMID- 21011082 TI - [Not Available]. PMID- 21011084 TI - [Not Available]. PMID- 21011083 TI - [Not Available]. PMID- 21011085 TI - [Not Available]. PMID- 21011086 TI - [Not Available]. PMID- 21011087 TI - [Not Available]. PMID- 21011088 TI - [Not Available]. PMID- 21011089 TI - [Not Available]. PMID- 21011090 TI - [Not Available]. PMID- 21011091 TI - [Not Available]. PMID- 21011092 TI - [Not Available]. PMID- 21011093 TI - [Not Available]. PMID- 21011094 TI - [Not Available]. PMID- 21011095 TI - Sprue in India; a clinical survey of 600 cases. PMID- 21011096 TI - Outbreak of Weil's disease in the British Army in Italy; clinical study. PMID- 21011097 TI - Primary tuberculosis in childhood. PMID- 21011098 TI - Intelligence and infant mortality in problem families. PMID- 21011099 TI - Spontaneous haemothorax. PMID- 21011100 TI - Fatal aorticoesophageal fistula from a swallowed piece of bone. PMID- 21011101 TI - Human gammaglobulin. PMID- 21011102 TI - Stethoscope versus X rays. PMID- 21011103 TI - [Not Available]. PMID- 21011104 TI - [Not Available]. PMID- 21011105 TI - [Not Available]. PMID- 21011106 TI - [Not Available]. PMID- 21011107 TI - [Not Available]. PMID- 21011108 TI - [Not Available]. PMID- 21011109 TI - [Not Available]. PMID- 21011110 TI - [Not Available]. PMID- 21011111 TI - [Not Available]. PMID- 21011112 TI - [Not Available]. PMID- 21011113 TI - [Not Available]. PMID- 21011114 TI - [Not Available]. PMID- 21011115 TI - [Not Available]. PMID- 21011116 TI - [Not Available]. PMID- 21011117 TI - [Not Available]. PMID- 21011118 TI - [Not Available]. PMID- 21011120 TI - [Not Available]. PMID- 21011119 TI - [Not Available]. PMID- 21011121 TI - [Not Available]. PMID- 21011122 TI - [Not Available]. PMID- 21011123 TI - [Not Available]. PMID- 21011124 TI - [Not Available]. PMID- 21011125 TI - [Not Available]. PMID- 21011126 TI - [Not Available]. PMID- 21011127 TI - [Not Available]. PMID- 21011128 TI - [Not Available]. PMID- 21011129 TI - [Not Available]. PMID- 21011130 TI - [Not Available]. PMID- 21011131 TI - [Not Available]. PMID- 21011132 TI - [Not Available]. PMID- 21011133 TI - [Not Available]. PMID- 21011134 TI - [Not Available]. PMID- 21011136 TI - [Not Available]. PMID- 21011135 TI - [Not Available]. PMID- 21011137 TI - [Not Available]. PMID- 21011138 TI - [Not Available]. PMID- 21011139 TI - [Not Available]. PMID- 21011140 TI - [Not Available]. PMID- 21011141 TI - [Not Available]. PMID- 21011142 TI - [Not Available]. PMID- 21011143 TI - The control of experimental pneumonia with penicillin; comparison of inhalation and injection therapy. PMID- 21011144 TI - Sodium caprylate; a new and effective treatment for dermatomycosis of the feet. PMID- 21011145 TI - The bacteriostatic and bactericidal effects of fatty acid salts on bacteria in broth cultures. PMID- 21011147 TI - Medical treatment of empyema. PMID- 21011146 TI - Observations on the incidence of Tinea pedis in a group of men entering military life. PMID- 21011148 TI - Pulmonary embolism. PMID- 21011149 TI - The evolution of industrial medicine. PMID- 21011150 TI - Liver function tests. PMID- 21011151 TI - Antihormones. PMID- 21011152 TI - Skin-test reactions of medical students. PMID- 21011153 TI - The management of acute craniocerebral injuries. PMID- 21011154 TI - Tonsils and aging. PMID- 21011155 TI - Physiopathology and surgical treatment of congenital cardiovascular defects. PMID- 21011156 TI - The treatment of aneurysms and arteriovenous fistulas. PMID- 21011157 TI - The hormonal treatment of prostatic malignancy. PMID- 21011158 TI - New absorbable hemostatic agents. PMID- 21011159 TI - The importance of plasma protein changes and haemoconcentration in shock. PMID- 21011160 TI - Speeding up action of oxalic acid on the process of wound healing. PMID- 21011161 TI - The relation of ascorbic acid intake to gingivitis. PMID- 21011162 TI - The treatment of defects of the long bones by cancellous chip bone grafts. PMID- 21011163 TI - Adenolymphoma of the salivary glands. PMID- 21011164 TI - The heart in hypertension since the days of Richard Bright. PMID- 21011165 TI - Chronic prostatitis associated with non-specific urethritis. PMID- 21011166 TI - Chest x-ray survey of repatriated prisoners of war from Japanese camps. PMID- 21011167 TI - Circulation failure in hunger oedema. PMID- 21011168 TI - Jaundice in infancy. PMID- 21011169 TI - Treatment with vitamin B of a special type of vesical atony. PMID- 21011170 TI - The columnized medical chart. PMID- 21011171 TI - Dupuytren's contracture. PMID- 21011172 TI - Restropin factor in cancer in relation to the reticuloendothelial system. PMID- 21011173 TI - Teratoid tumour and carcinoma of the testis. PMID- 21011174 TI - Anuria due to a large hydronephrosis. PMID- 21011175 TI - An emergency carriage for the immediate treatment of serious casualties. PMID- 21011176 TI - Highlights in the history of the Boston Lying-In Hospital. PMID- 21011177 TI - Problems of the neuroses; an experimental approach. PMID- 21011178 TI - Hepatitis; newer developments. PMID- 21011179 TI - Penicillin in the treatment of gonorrhea; results with six hundred and seventy five women. PMID- 21011180 TI - Vascular mechanisms of terminal shock. PMID- 21011181 TI - Obscure, incarcerated, or strangulated hernia as a cause of intestinal obstruction; a report of four cases. PMID- 21011182 TI - Absence of pituitary failure in fat boys with testicular deficiency. PMID- 21011183 TI - Cervical periarthritis; diagnosis and treatment. PMID- 21011184 TI - Edema; clinical significance. PMID- 21011185 TI - Von Gierke's glycogen disease; report of two cases. PMID- 21011186 TI - Meeting the tuberculosis problem today. PMID- 21011187 TI - Private physician responsibility in tuberculosis control. PMID- 21011188 TI - Chest x-ray in industrial pre-placement examinations. PMID- 21011189 TI - Pulmonary pathology in rejectees; a survey of 100,000 photoroentgenograms performed at the induction center in Connecticut. PMID- 21011190 TI - Cancer of the prostate in Connecticut. PMID- 21011191 TI - Notes on the history of orthopedic surgery in Connecticut. PMID- 21011193 TI - The physiology of migraine. PMID- 21011192 TI - Malignant dermoid of the ovary. PMID- 21011194 TI - Total cystectomy; four case reports. PMID- 21011196 TI - Rober's congenital heart disease. PMID- 21011195 TI - Chronic nephritis with metastatic calcification. PMID- 21011197 TI - Familial Mediterranean target oval cell (Cooley's) anemia. PMID- 21011198 TI - Streptomycin; a review of the literature. PMID- 21011199 TI - The treatment of duodenal ulcer. PMID- 21011200 TI - A clinical review of cancer of the breast and antecedent chronic conditions. PMID- 21011201 TI - Post-operative pulmonary complications. PMID- 21011202 TI - The use of penicillin in acute infections of the hand. PMID- 21011203 TI - Factors modifying the clinical features and course of glomerulonephritis. PMID- 21011204 TI - The consultant and specialist. PMID- 21011205 TI - Medical implications of atomic energy. PMID- 21011206 TI - Periarteritis nodosa; case report. PMID- 21011207 TI - Femoral thrombosis following gangrenous appendicitis. PMID- 21011208 TI - Observations on nocturnal gastric secretion. PMID- 21011209 TI - Atrophic arthritis; diagnosis and medical management. PMID- 21011210 TI - Compound fractures. PMID- 21011211 TI - Medical care for veterans. PMID- 21011212 TI - Thrombosis of the deep veins of the lower extremities. PMID- 21011213 TI - The Ganser syndrome; a case study. PMID- 21011214 TI - The action of shock therapy in the light of clinical observation. PMID- 21011215 TI - How the employer may evaluate his medical service. PMID- 21011216 TI - Nasal allergy. PMID- 21011217 TI - Vasomotor rhinitis. PMID- 21011218 TI - Tuberculous cavities and pneumoperitoneum. PMID- 21011219 TI - A case of papilloma of the common bile duct. PMID- 21011220 TI - Insomnia as an early sign of brain abscess. PMID- 21011221 TI - Toxic manifestations of thiouracil therapy. PMID- 21011222 TI - Chronic brucellosis; success of treatment with brucellin. PMID- 21011223 TI - Range of blood pressure in hypertension. PMID- 21011224 TI - The treatment of influenzal meningitis. PMID- 21011225 TI - Central nervous system complications associated with kernicterus. PMID- 21011226 TI - Pencillin in spinal fluid after intravenous administration. PMID- 21011227 TI - Endometriosis causing intestinal obstruction. PMID- 21011228 TI - The clinical toxicity of thiouracil; a survey of 5,745 cases. PMID- 21011229 TI - BIOLOGIC warfare. PMID- 21011230 TI - The returning injured soldier. PMID- 21011231 TI - VENEREAL disease. PMID- 21011233 TI - Tachycardia and its treatment. PMID- 21011232 TI - The latest treatment of malaria. PMID- 21011234 TI - [Not Available]. PMID- 21011235 TI - [Not Available]. PMID- 21011236 TI - Gastric acidity in orogenital syndrome. PMID- 21011237 TI - Preliminary investigations on the spreading properties of cerebrospinal fluid. PMID- 21011238 TI - Calcium and coagulation defects. PMID- 21011239 TI - Correlation of blood sugar values with glycosuria and their relation to treatment. PMID- 21011240 TI - On the interpretation of Wassermann and Kahn reactions. PMID- 21011241 TI - Blood matching for transfusion. PMID- 21011242 TI - Tonsillectomy; its use and abuse in children. PMID- 21011244 TI - Headache in amoebiasis. PMID- 21011243 TI - The Arabian background of modern surgery. PMID- 21011245 TI - Results of administration of varying doses of sodium bromide. PMID- 21011246 TI - Foot deformities corrected by rubber band traction. PMID- 21011247 TI - Early diagnosis and treatment of rheumatic fever. PMID- 21011248 TI - Laennec's cirrhosis with patency of the umbilical vein. PMID- 21011249 TI - Hypnosis without voodooism. PMID- 21011250 TI - The pathologic physiology of Paget's disease. PMID- 21011252 TI - Renal ectopia. PMID- 21011251 TI - Prevention and treatment of pulmonary embolism. PMID- 21011253 TI - Renal decapsulation. PMID- 21011254 TI - The use of lanatoside C in the treatment of congestive heart failure. PMID- 21011255 TI - Treatment of burns. PMID- 21011256 TI - A new interpretation of some so-called positive patch tests; with special reference to metals used in industry. PMID- 21011257 TI - Hypoglycemia, secondary to islet cell adenoma of the pancreas; with report of a case. PMID- 21011258 TI - Appendicitis; a statistical study of the death rate in Detroit and at Mount Carmel Mercy Hospital. PMID- 21011260 TI - Leptotrichosis conjunctivae. PMID- 21011259 TI - Vasodilators in peripheral ocular angiospasm. PMID- 21011261 TI - Traumatic convulsive seizures. PMID- 21011262 TI - A roentgen-ray classification of the pneumonias with special reference to the tissues involved. PMID- 21011263 TI - Volvulus of the stomach; report of a case. PMID- 21011264 TI - Hemorrhage and shock in obstetrics. PMID- 21011266 TI - Toxemia of pregnancy. PMID- 21011265 TI - Chronic sinusitis; a safe management and treatment. PMID- 21011267 TI - Medical complications of pregnancy. PMID- 21011268 TI - Some aspects of prenatal care. PMID- 21011269 TI - Management of labor. PMID- 21011270 TI - Care of the newborn. PMID- 21011271 TI - Postpartum care. PMID- 21011272 TI - Bread. PMID- 21011273 TI - Synergic action of penicillin and sulphathiazole on Bacterium typhosum. PMID- 21011274 TI - Hyperventilation asthma. PMID- 21011275 TI - Local penicillin for throat infections. PMID- 21011276 TI - Human pulmonary tuberculosis due to avian tubercle bacilli; report of a case. PMID- 21011277 TI - Control of Sonne dysentery with succinylsulphathiazole. PMID- 21011278 TI - Dengue group of fevers in India. PMID- 21011279 TI - Gunshot wound of both orbits; report of a case. PMID- 21011281 TI - LONDON pride. PMID- 21011280 TI - CARBON 13. PMID- 21011282 TI - Croydon Obstetric Service; results in 18,600 booked deliveries. PMID- 21011283 TI - Infection in day nurseries. PMID- 21011284 TI - Hepatitis after penicillin injections. PMID- 21011285 TI - Tetanus in the African and European theatres of war, 1939-1945. PMID- 21011286 TI - Tuberculous rheumatism. PMID- 21011287 TI - Difficulties in the diagnosis of rheumatic fever. PMID- 21011288 TI - Continuous epithelisation on large denuded areas. PMID- 21011289 TI - Erysipeloid. PMID- 21011290 TI - Erysipeloid of Rosenbach; response to penicillin. PMID- 21011291 TI - Non-greasy jelly base for penicillin. PMID- 21011292 TI - Incidence of scabies; results of rapid surveys in school, factory, and hospital. PMID- 21011293 TI - Effect of large doses of alkali on kidney function. PMID- 21011294 TI - A medical officer in Hong Kong. PMID- 21011295 TI - Post cholecystectomy syndrome. PMID- 21011296 TI - A case of anophthalmos. PMID- 21011297 TI - Flat foot. PMID- 21011298 TI - Two cases of fatal pulmonary embolism associated with anaesthesia. PMID- 21011299 TI - A case of infantile tetany. PMID- 21011300 TI - [Not Available]. PMID- 21011301 TI - [Not Available]. PMID- 21011302 TI - [Not Available]. PMID- 21011303 TI - [Not Available]. PMID- 21011305 TI - [Not Available]. PMID- 21011304 TI - [Not Available]. PMID- 21011306 TI - [Not Available]. PMID- 21011307 TI - Laboratory tests for vitamin K deficiency. PMID- 21011309 TI - Hormones. PMID- 21011308 TI - Vitamin C in general practice. PMID- 21011310 TI - The use of estrogenic hormone in prostatic hypertrophy. PMID- 21011311 TI - [Not Available]. PMID- 21011312 TI - [Not Available]. PMID- 21011313 TI - [Not Available]. PMID- 21011314 TI - Natural bacterial agglutinins in the child's serum. PMID- 21011315 TI - Amoebiasis in New Guinea, 1943-1944. PMID- 21011317 TI - RECENT work in Russia on typhus exanthematicus. PMID- 21011316 TI - A case of carcinoma of the renal pelvis. PMID- 21011318 TI - Gastro-enteritis and dysentery in children; the bacteriology of cases caused by Salmonella and dysentery organisms. PMID- 21011319 TI - The New Guinea campaign. PMID- 21011320 TI - Prescribing in the metric system. PMID- 21011321 TI - Fluid balance in scrub typhus. PMID- 21011322 TI - A case of pneumococcal meningitis successfully treated with penicillin. PMID- 21011323 TI - Aviation medicine. PMID- 21011324 TI - The modern treatment of pulmonary tuberculosis in Australia. PMID- 21011326 TI - On the prickly heat. PMID- 21011325 TI - Some laboratory findings pertaining to the clinical use of penicillin. PMID- 21011327 TI - Physiotherapy in general practice. PMID- 21011329 TI - A syndrome in vivax malaria probably due to spontaneous subcapsular haemorrhage of the spleen. PMID- 21011328 TI - Hirst's haemagglutination phenomenon exhibited by Rickettsia orientalis (syn. tsutsugamushi). PMID- 21011330 TI - Haemopericardium as an autopsy finding. PMID- 21011331 TI - A case of severe burns. PMID- 21011332 TI - A case of fatal stabbing by a stingray. PMID- 21011333 TI - The seeds of Macrozamia denisoni. PMID- 21011334 TI - Modern treatment of toxaemias of pregnancy. PMID- 21011336 TI - The strength of the nation is in its homes. PMID- 21011335 TI - Are we suffering from chronic malnutrition? PMID- 21011337 TI - An investigation into kinaesthesia. PMID- 21011338 TI - The study of the effects of temperature upon the stability of penicillin in solution and ointment. PMID- 21011339 TI - Early controlled ambulation in the puerperium. PMID- 21011340 TI - Mental deficiency and psychological conditions in early childhood. PMID- 21011341 TI - The woman's problem in medical practice. PMID- 21011342 TI - Suggests a new dressing for severe burns and for extensive abrasions. PMID- 21011343 TI - Sexual neurosis in soldiers is not an uncommon condition. PMID- 21011344 TI - Advocates immediate replacement of uterus. PMID- 21011345 TI - The management of breech presentations. PMID- 21011346 TI - The common cold. PMID- 21011347 TI - Surgery in infancy and childhood. PMID- 21011348 TI - A forgotten form of arthritis. PMID- 21011349 TI - Absence of vagina; case report. PMID- 21011350 TI - Adenocarcinoma of the ascending colon; case report. PMID- 21011351 TI - The problem of medicine in rural health. PMID- 21011352 TI - Lumbar sympathetic block and that postphlebitic leg. PMID- 21011353 TI - Medical experiences at Dachau. PMID- 21011354 TI - Embolism of the right femoral artery; report of case. PMID- 21011355 TI - The treatment of neurosurgical cases in an overseas hospital. PMID- 21011356 TI - A review of sedation. PMID- 21011357 TI - Sodium citrate therapy in lead encephalopathy; case report in an infant. PMID- 21011358 TI - Emergencies of the neonatal period. PMID- 21011359 TI - Fifty years of radiology from Roentgen to the era of atomic power. PMID- 21011360 TI - Hodgkin's disease; treatment and prognosis. PMID- 21011361 TI - The Wolff-Parkinson-White syndrome. PMID- 21011362 TI - Syncope in blood donors. PMID- 21011363 TI - Electroencephalographic studies in diabetes mellitus. PMID- 21011364 TI - Parathyroid adenoma; clinicopathological exercises. PMID- 21011366 TI - [Not Available]. PMID- 21011365 TI - Ewing's sarcoma of pubis; clinicopathological exercises. PMID- 21011367 TI - [Not Available]. PMID- 21011368 TI - Observations made during a poliomyelitis epidemic in 1944 in the Hornell State Health District, New York. PMID- 21011369 TI - Diagnosis and management of certain tropical diseases in returning veterans. PMID- 21011370 TI - A review of the various methods used in the treatment of phlebothrombosis of the extremities. PMID- 21011371 TI - Group practice. PMID- 21011372 TI - Functions of a blood bank. PMID- 21011373 TI - Artificial pneumoperitoneum by cul-de-sac puncture. PMID- 21011374 TI - The radiologic diagnosis of ectopic pregnancy. PMID- 21011375 TI - Current thoughts on carcinoma of rectum. PMID- 21011376 TI - Progress in our knowledge of hydatid disease. PMID- 21011377 TI - The feeding of school children with the health dinner; report of an experiment. PMID- 21011378 TI - The incidence in New Zealand of pulmonary tuberculosis in pregnant women. PMID- 21011379 TI - Calcification of the left auricle; report of a case. PMID- 21011380 TI - Eosinophilic granuloma of bone; report of a case. PMID- 21011381 TI - The incidence and diagnosis of amoebic dysentery in the 2nd N.Z. Expeditionary Force. PMID- 21011382 TI - Arthritis complicating meningitis. PMID- 21011383 TI - Folic acid (L. casei factor), an essential pan-hematopoietic factor; experimental and clinical studies. PMID- 21011384 TI - Some psychiatric notes on the war in the Pacific. PMID- 21011385 TI - Fatal case of sodium nitrite poisoning. PMID- 21011386 TI - Battle wound of the thigh complicated by gas gangrene in a case of hereditary hemorrhagic thromb asthenia. PMID- 21011387 TI - Air embolism following uterotubal insufflation; report of two cases. PMID- 21011388 TI - Notes on heart failure. PMID- 21011389 TI - Early ambulation in abdomino-pelvic surgery. PMID- 21011390 TI - The treatment of rheumatic chorea. PMID- 21011391 TI - Closure of surface defects of the hand. PMID- 21011392 TI - Otorhinoplasty in the field of otolaryngology. PMID- 21011393 TI - Acute otitis media. PMID- 21011394 TI - Spindle-cell sarcoma of the chest wall. PMID- 21011395 TI - Symptomatic control of urticaria and its equivalents by benadryl; report of forty seven consecutive treated cases. PMID- 21011396 TI - Case finding in large cities. PMID- 21011397 TI - Tuberculosis in Negroes. PMID- 21011398 TI - Fundamental information on the mechanism of specific tuberculoimmunity. PMID- 21011399 TI - Dietary aspects of tuberculosis. PMID- 21011400 TI - Season and tuberculosis. PMID- 21011401 TI - Can the specific effects of housing on tuberculosis and health be measured? PMID- 21011402 TI - The family problem of the tuberculous patient. PMID- 21011403 TI - Education of public authorities and the laity in tuberculosis. PMID- 21011404 TI - Tuberculosis in children. PMID- 21011405 TI - Tuberculosis as a school problem. PMID- 21011406 TI - The practical application of instructional methods for tuberculosis education in schools. PMID- 21011407 TI - Tuberculosis in industry from the viewpoint of the physician in industry. PMID- 21011408 TI - The problem of tuberculosis in industry from the viewpoint of labor. PMID- 21011409 TI - Management's interest in tuberculosis control in industry. PMID- 21011410 TI - Pneumothorax therapy, including ambulatory pneumothorax treatment. PMID- 21011411 TI - Surgical treatment of pulmonary tuberculosis. PMID- 21011413 TI - Rehabilitation of the tuberculous. PMID- 21011412 TI - Follow-up problems, including the chronic open case. PMID- 21011414 TI - Application of principles discussed at this conference to metropolitan areas; the national viewpoint. PMID- 21011415 TI - The local situation in Chicago. PMID- 21011416 TI - The principles and organization of treatment. PMID- 21011417 TI - Tuberculosis in Chicago, 1945. PMID- 21011418 TI - Total pancreatectomy; a symposium presenting four successful cases and a report on metabolic observations. PMID- 21011419 TI - A therapeutic trial of penicillin in infective conditions of the skin. PMID- 21011420 TI - The nicotinic acid content of blood in health and disease. PMID- 21011421 TI - The hereditary and familial aspects of exophthalmic goitre and nodular goitre. PMID- 21011422 TI - Gastric pain. PMID- 21011423 TI - A technique for demonstrating oesophageal varices. PMID- 21011424 TI - Enuresis. PMID- 21011426 TI - [Not Available]. PMID- 21011425 TI - [Not Available]. PMID- 21011427 TI - [Not Available]. PMID- 21011428 TI - [Not Available]. PMID- 21011429 TI - [Not Available]. PMID- 21011430 TI - [Not Available]. PMID- 21011431 TI - [Not Available]. PMID- 21011433 TI - [Not Available]. PMID- 21011432 TI - [Not Available]. PMID- 21011434 TI - [Not Available]. PMID- 21011435 TI - [Not Available]. PMID- 21011436 TI - [Not Available]. PMID- 21011437 TI - [Not Available]. PMID- 21011438 TI - [Not Available]. PMID- 21011439 TI - [Not Available]. PMID- 21011440 TI - [Not Available]. PMID- 21011441 TI - [Not Available]. PMID- 21011442 TI - [Not Available]. PMID- 21011443 TI - [Not Available]. PMID- 21011444 TI - [Not Available]. PMID- 21011446 TI - [Not Available]. PMID- 21011445 TI - [Not Available]. PMID- 21011447 TI - [Not Available]. PMID- 21011448 TI - [Not Available]. PMID- 21011449 TI - [Not Available]. PMID- 21011450 TI - [Not Available]. PMID- 21011451 TI - [Not Available]. PMID- 21011452 TI - [Not Available]. PMID- 21011453 TI - [Not Available]. PMID- 21011454 TI - [Not Available]. PMID- 21011455 TI - [Not Available]. PMID- 21011456 TI - [Not Available]. PMID- 21011457 TI - [Not Available]. PMID- 21011458 TI - [Not Available]. PMID- 21011459 TI - [Not Available]. PMID- 21011460 TI - [Not Available]. PMID- 21011461 TI - Recent advances in knowledge of the Rh blood factors, with special reference to the clinical applications. PMID- 21011462 TI - Post-war objectives of tuberculosis control. PMID- 21011463 TI - George Eliot's Quarry for Middlemarch; an unpublished notebook revealing her medical sources. PMID- 21011464 TI - Benjamin Rush terminates a post-war mutiny among troops demanding their discharge. PMID- 21011465 TI - [Not Available]. PMID- 21011466 TI - [Not Available]. PMID- 21011467 TI - [Not Available]. PMID- 21011468 TI - [Not Available]. PMID- 21011469 TI - [Not Available]. PMID- 21011470 TI - [Not Available]. PMID- 21011471 TI - [Not Available]. PMID- 21011472 TI - [Not Available]. PMID- 21011473 TI - [Not Available]. PMID- 21011474 TI - [Not Available]. PMID- 21011475 TI - [Not Available]. PMID- 21011476 TI - [Not Available]. PMID- 21011477 TI - [Not Available]. PMID- 21011478 TI - [Not Available]. PMID- 21011479 TI - [Not Available]. PMID- 21011480 TI - [Not Available]. PMID- 21011481 TI - [Not Available]. PMID- 21011482 TI - [Not Available]. PMID- 21011483 TI - Operation for habitual albuluxation. PMID- 21011484 TI - [Not Available]. PMID- 21011485 TI - [Not Available]. PMID- 21011486 TI - [Not Available]. PMID- 21011487 TI - [Not Available]. PMID- 21011488 TI - [Not Available]. PMID- 21011489 TI - [Not Available]. PMID- 21011491 TI - [Not Available]. PMID- 21011490 TI - [Not Available]. PMID- 21011492 TI - [Not Available]. PMID- 21011493 TI - [Not Available]. PMID- 21011494 TI - [Not Available]. PMID- 21011495 TI - [Not Available]. PMID- 21011496 TI - [Not Available]. PMID- 21011497 TI - [Not Available]. PMID- 21011498 TI - [Not Available]. PMID- 21011500 TI - Compound fractures. PMID- 21011499 TI - Some reflections of an industrial medical officer. PMID- 21011501 TI - Volkmann's ischemic contracture. PMID- 21011502 TI - Eclampsia. PMID- 21011503 TI - The blood sedimentation rate. PMID- 21011504 TI - An investigation of allergy in routine nose and throat practice; a report of one hundred private cases. PMID- 21011505 TI - Prophylaxis against cervical malignancy. PMID- 21011506 TI - Unsuspected tuberculosis. PMID- 21011507 TI - Postage stamps as a mode of transmitting bacteria. PMID- 21011508 TI - The value of message in rheumatoid arthritis. PMID- 21011509 TI - Exploration of cystic and sclerotic ovaries as a means of preserving their function. PMID- 21011510 TI - Sterility and sub-fertility. PMID- 21011511 TI - The use of synthetic oestrogens in malignant and non-malignant disease. PMID- 21011512 TI - Introspection. PMID- 21011513 TI - Ammonium chloride in the prevention of stilbestrol nausea. PMID- 21011514 TI - Why a public health career. PMID- 21011515 TI - Continuous caudal analgesia in obstetrics as viewed by mother, baby and physician. PMID- 21011516 TI - Severe erythema multiforme; case report. PMID- 21011517 TI - EFFECT of the environment on respiratory diseases in the Army. PMID- 21011518 TI - VETERINARY service. PMID- 21011519 TI - Knee-shoulder position unit for sigmoidoscopy. PMID- 21011520 TI - Typhus in lower Bavaria. PMID- 21011521 TI - Traction for bilateral leg amputees. PMID- 21011522 TI - Training Medical Department enlisted men. PMID- 21011523 TI - Treatment of aneurysms and arteriovenous fistulas. PMID- 21011524 TI - Clinical survey of 86 cases of scrub typhus. PMID- 21011525 TI - The Rorschach test in the differential diagnosis of cerebral concussion and psychoneurosis. PMID- 21011526 TI - Transportation of patients with fracture of femur. PMID- 21011527 TI - Reconditioning program in a station hospital. PMID- 21011528 TI - Cardiac pathology as related to anesthesia. PMID- 21011529 TI - Responsibilities of the medical supply officer. PMID- 21011530 TI - Blood groups in Air Forces basic trainees. PMID- 21011531 TI - The diagnosis of acute Coccidioides immitis infections. PMID- 21011532 TI - Treatment of hysteria in a forward echelon. PMID- 21011533 TI - Trench foot: prognosis and disposition. PMID- 21011534 TI - Closed ward psychiatric reconditioning. PMID- 21011535 TI - Localization of intraocular foreign bodies. PMID- 21011536 TI - The processing of newly arrived patients. PMID- 21011538 TI - Functional partial dentures. PMID- 21011539 TI - Estimation of bacterial susceptibility to penicillin. PMID- 21011537 TI - Determination of halogenated hydrocarbons in air. PMID- 21011540 TI - Infectivity of dengue serums transported in ordinary ice by air. PMID- 21011541 TI - Tracheobronchial catheter aspiration. PMID- 21011542 TI - Knuckle bender splint. PMID- 21011543 TI - Rupture of intestine through intact abdominal wall. PMID- 21011544 TI - Positive pressure oxygen therapy in treatment of pulmonary edema caused by chlorine gas. PMID- 21011545 TI - Simple laboratory test as an aid in recognizing early hepatitis. PMID- 21011546 TI - Determining prothrombin clotting time using Russell's viper venom as thromboplastic substance. PMID- 21011547 TI - Surgical advances during the war. PMID- 21011548 TI - The development and the results of transfusion in the treatment of battle casualties. PMID- 21011549 TI - Orthopaedic lessons of the war. PMID- 21011550 TI - Surgery at a casualty clearing station. PMID- 21011551 TI - The Tobruk plaster. PMID- 21011552 TI - The future of surgery in the Army. PMID- 21011553 TI - Surgical nursing in wartime. PMID- 21011554 TI - Repatriated allied prisoners of war and internees. PMID- 21011555 TI - Dietary deficiency diseases among prisoners of war. PMID- 21011556 TI - Bat malaria. PMID- 21011557 TI - Studies on mosquitoes of the genus Haemagogus in Colombia (Diptera, Culicidae). PMID- 21011558 TI - PERIODICITY of influenza. PMID- 21011559 TI - Studies on the specificity of intradermal tests in the diagnosis of filariasis. PMID- 21011560 TI - The effect of immunization against lactobacilli and acidogenic cocci on the tooth flora of the rat. PMID- 21011561 TI - Epidemiological and experimental observations of poliomyelitis in New York City (1943-1944). PMID- 21011562 TI - EFFECT of double-bunking in barracks on the incidence of respiratory disease. PMID- 21011563 TI - Differences among strains of poliomyelitis virus in Macaca mulatta. PMID- 21011564 TI - Influenza. PMID- 21011566 TI - Diet during pregnancy. PMID- 21011565 TI - Prenatal nutrition. PMID- 21011567 TI - TRICHINOSIS and undercooked pork. PMID- 21011568 TI - Tuberculosis control. PMID- 21011569 TI - Tuberculin testing. PMID- 21011570 TI - Pasteurization in the province of Quebec; with special reference to Montreal. PMID- 21011571 TI - Observations on the calcium content of cow's milk. PMID- 21011572 TI - Composition of commercial ice cream. PMID- 21011573 TI - Atownship public health centre in Ontario. PMID- 21011574 TI - Health education. PMID- 21011575 TI - Social factors and mental health. PMID- 21011576 TI - Hygiene of the body. PMID- 21011577 TI - Indoor storms. PMID- 21011578 TI - Children without families. PMID- 21011579 TI - Difficulties in sex education. PMID- 21011580 TI - The importance of water. PMID- 21011581 TI - Some obstructive conditions in the upper abdomen in infancy. PMID- 21011582 TI - Mass radiography; a review of a first year's working. PMID- 21011583 TI - Aspects of hygiene and sanitation in the Royal Navy. PMID- 21011584 TI - The unfit house. PMID- 21011585 TI - New remedies in disinfestation. PMID- 21011586 TI - The use of DDT as an insecticide. PMID- 21011587 TI - David and Goliath; a plea for the individual in social medicine. PMID- 21011588 TI - The movable dwelling; is it adequately controlled? PMID- 21011589 TI - Rodent control. PMID- 21011590 TI - The nature, causes, incidence, pathology and sociology of mental deficiency. PMID- 21011591 TI - The economic and public health advantages of centralized slaughtering. PMID- 21011592 TI - Design of sewers to facilitate flow. PMID- 21011593 TI - Small sludge elutriation plants. PMID- 21011594 TI - Preliminary greenhouse studies of digested sludge as a fertilizer. PMID- 21011595 TI - Experience in grit removal and handling at Racine, Wis. PMID- 21011596 TI - The toxicity thresholds of various sodium salts determined by the use of Daphnia magna. PMID- 21011597 TI - The trickling filter and its operation. PMID- 21011598 TI - Sewage plant records and operating reports. PMID- 21011599 TI - The effect of industrial wastes on sewage treatment. PMID- 21011600 TI - Use of effluent water in sewage treatment plants. PMID- 21011601 TI - A rare anomaly in the elbow; patella cubiti. PMID- 21011602 TI - An attempt at the roentgenologic visualization of coronary blood vessels in man. PMID- 21011603 TI - [Not Available]. PMID- 21011604 TI - Studies on the Brown-Pearce rabbit-carcinoma with the aid of radioactive isotopes. PMID- 21011605 TI - The roentgen picture of the tabetic arthropathies and affections of bones. PMID- 21011606 TI - Necrosis of the renal papillae following retrograde pyelography. PMID- 21011608 TI - Observations on the technique of phlebography. PMID- 21011607 TI - On radio-surgery of tumor metastases in the lymph glands of the neck. PMID- 21011609 TI - The treatment of tumors of the urinary bladder. PMID- 21011610 TI - Protection against high energy roentgen rays. PMID- 21011611 TI - Experiences with the roentgen-ray tube. PMID- 21011612 TI - Early American roentgenograms. PMID- 21011613 TI - The roentgen examination in occupational diseases of the lungs; a historical discussion of its use. PMID- 21011614 TI - Fifty years of roentgen rays in gastroenterology. PMID- 21011615 TI - Roentgen diagnosis in urologic disorders. PMID- 21011616 TI - Background and beginning of cholecystography. PMID- 21011617 TI - The development of modern neuroroentgenology. PMID- 21011618 TI - Early history of roentgenology of the sinuses. PMID- 21011619 TI - History of the roentgen ray in the study of the heart. PMID- 21011620 TI - The history of the use of the roentgen ray in warfare. PMID- 21011621 TI - The Army roentgen-ray equipment problem. PMID- 21011622 TI - The history of dosimetry in roentgen therapy. PMID- 21011623 TI - Utilization of antibody for the localization of metals and dyes in the tissues. PMID- 21011624 TI - Salient factors in the treatment of Hodgkin's disease and lymphosarcoma with roentgen rays. PMID- 21011625 TI - Biological evaluation of 20 million volt roentgen rays; acute roentgen death in mice. PMID- 21011626 TI - Hookworm disease; a small intestinal study. PMID- 21011627 TI - Pulmonary changes in carbon tetrachloride poisoning. PMID- 21011628 TI - Esophagobronchial fistula through an esophageal diverticulum. PMID- 21011629 TI - Rickets and infantile scurvy occurring in a case of osteogenesis imperfecta. PMID- 21011630 TI - Generalized leontiasis ossea. PMID- 21011631 TI - The histologic effects of radiophosphorus on normal and lymphomatous mice. PMID- 21011632 TI - The significance of the volume dose. PMID- 21011633 TI - [Not Available]. PMID- 21011634 TI - [Not Available]. PMID- 21011635 TI - [Not Available]. PMID- 21011636 TI - An x-ray study of the development of pulmonary echinococcus. PMID- 21011637 TI - [Not Available]. PMID- 21011638 TI - [Not Available]. PMID- 21011639 TI - [Not Available]. PMID- 21011640 TI - Superficial burns of skin and eyes from scattered cathode rays. PMID- 21011641 TI - Roentgenology of the draining bronchi from tuberculous cavities. PMID- 21011642 TI - A study of the ureters in bladder neck obstructions. PMID- 21011643 TI - Diagnosis of pes planus by x-ray. PMID- 21011644 TI - Pneumoconiosis due to cotton dust (byssinosis). PMID- 21011645 TI - An unusual case of multiple chondromata. PMID- 21011646 TI - Roentgenographic demonstration of concretions in the submandibular glandular duct by use of intraoral films. PMID- 21011647 TI - The tolerance dose or tolerance intensity. PMID- 21011648 TI - Radiation injury. PMID- 21011650 TI - Human factors. PMID- 21011649 TI - Genetic injury. PMID- 21011651 TI - X-ray protection in industrial fluoroscopy. PMID- 21011652 TI - Materials and methods of x-ray protection. PMID- 21011653 TI - Important dividing wall between caudal herniation and prolapse of abdominal or pelvic viscera. PMID- 21011654 TI - Urinary incontinence; with special reference to certain factors which are necessary in the cure of this condition. PMID- 21011655 TI - Essential hypertension; an examination of its mechanism in relation to surgical treatment. PMID- 21011656 TI - Bronchiectasis and its surgical considerations. PMID- 21011657 TI - Evaluation of the treatment of cancer of the breast; with a suggestion for its modification. PMID- 21011658 TI - Benign tumors of the vulva. PMID- 21011659 TI - Treatment of compression fracture of the spine, with a report of 160 cases at Fordham Hospital. PMID- 21011660 TI - March (fatigue) fractures of the long bones of the lower extremity and pelvis. PMID- 21011661 TI - Penicillin therapy as an adjunct to genitourinary surgery; report of 11 cases. PMID- 21011662 TI - The critically burned patient. PMID- 21011663 TI - The use of a blood-kaolin-penicillin paste in the treatment of varicose and torpid leg ulcers. PMID- 21011664 TI - Bilateral fracture of the scapula. PMID- 21011665 TI - Perforated peptic ulcer; a series of 28 cases. PMID- 21011666 TI - Circumscribed post-traumatic osteoporosis of the lower ends of the radius and ulna. PMID- 21011667 TI - Tuberculosis of the third portion of the duodenum. PMID- 21011668 TI - Ischiofemoral arthrodesis with pseudoarthrosis. PMID- 21011669 TI - Left-sided appendicitis in a dextrocardiac patient. PMID- 21011670 TI - Massive enlargement of the prostate. PMID- 21011671 TI - Acute mesenteric occlusion. PMID- 21011672 TI - Glimpses of vascular surgery on the coral reefs of the southwestern Pacific. PMID- 21011673 TI - Variations in blood supply of liver, gallbladder, stomach, duodenum and pancreas; summary based on one hundred dissections. PMID- 21011674 TI - Bone plastic reamputation. PMID- 21011675 TI - Bone plastic reamputation of the thigh. PMID- 21011676 TI - New method of articulation of the femur for difficult cases after fracture of the neck of the femur. PMID- 21011677 TI - Pilonidal dimple, sinus, cyst and abscess. PMID- 21011678 TI - Principles of skin grafting. PMID- 21011679 TI - Hernia into the duodenojejunal fossa (hernia of Treitz); report of three cases. PMID- 21011680 TI - Diabetic gangrene involving the sinuses. PMID- 21011681 TI - Uncomplicated cecitis; report of a case. PMID- 21011682 TI - Relation of gastric acidity to recurrent ulcers after partial gastrectomy. PMID- 21011683 TI - Surgery of the common bile duct. PMID- 21011684 TI - [Not Available]. PMID- 21011685 TI - [Not Available]. PMID- 21011686 TI - [Secondary hemorrhages following gunshot wounds]. PMID- 21011687 TI - [Contribution to the treatment of gunshot aneurysms]. PMID- 21011689 TI - [On the osteomyelitis of congelations]. PMID- 21011688 TI - [On prevention of gangrene of the extremities following ligature of the blood vessels]. PMID- 21011690 TI - [The treatment of causalgia by fasciculation]. PMID- 21011691 TI - [Our experience in the removal of foreign bodies of gunshot origin]. PMID- 21011692 TI - [Complications of penetrating wounds of the chest and their effects, after data of the evaco-hospitals of the People's commissariat of public health of Georgia]. PMID- 21011693 TI - [Surgical removal of gunshot foreign bodies of the lung]. PMID- 21011694 TI - [Closing of pneumothorax by pneumopexy in large defects of the thorax]. PMID- 21011695 TI - [Roentgenological data on the condition of the stomach and duodenum following an operation for perforating ulcer]. PMID- 21011696 TI - [The surgical treatment of wounds of the spine at the Army region]. PMID- 21011698 TI - [Damages of the lower extremities with wooden splints]. PMID- 21011697 TI - [Lesions of the spine with damages of the spinal cord]. PMID- 21011699 TI - [Concerning the plastic restoration of the fingers after traumatic destruction]. PMID- 21011700 TI - Operative closure of the patent ductus arteriosus. PMID- 21011701 TI - Blood amylase activity in pancreatitis and other diseases; a simple diagnostic aid. PMID- 21011702 TI - Amino acids in therapy of disease; parenteral and oral administrations compared. PMID- 21011703 TI - Repair of large abdominal defects by pedicled fascial flaps. PMID- 21011704 TI - Chemotherapy and control of infection among victims of the Cocoanut Grove disaster. PMID- 21011705 TI - Experience in the management of the abdominal wounds of warfare. PMID- 21011706 TI - The effects of pedicle jejunal transplants in the stomach on Mann-Williamson dogs. PMID- 21011707 TI - Primary carcinoma of the fallopian tubes. PMID- 21011708 TI - Spontaneous rupture of the spleen. PMID- 21011709 TI - Accidental transplantation of cancer in the operating room; with a case report. PMID- 21011710 TI - Intercorporal bone graft in spinal fusion after disc removal. PMID- 21011711 TI - The initial surgical treatment of penetrating wounds of the rectum. PMID- 21011712 TI - The use of curare in anesthesia for thoracic surgery; preliminary report. PMID- 21011713 TI - Governing the occupied areas of the South Pacific; wartime lessons and peacetime proposals. PMID- 21011714 TI - Social science and democratic policy. PMID- 21011716 TI - The influence of streptomycin and streptothricin on the intestinal flora of mice. PMID- 21011715 TI - First principles of rural rehabilitation. PMID- 21011717 TI - A broth dilution method of assaying streptothricin and streptomycin. PMID- 21011718 TI - Dehydrogenase characteristics of the pneumococci. PMID- 21011719 TI - Dissociants of lactobacilli. PMID- 21011720 TI - The in vitro and in vivo activity of streptomycin against Hemophilus pertussis. PMID- 21011721 TI - Acidity controlling antisepsis by weak acids. PMID- 21011722 TI - Diphtherial toxoid purified by absorption. PMID- 21011723 TI - The isolation of four Salmonella types from one carrier. PMID- 21011724 TI - A small jar for grinding tissue to be used with the Waring blender. PMID- 21011725 TI - The structure of Spirochaeta novyi as revealed by the electron microscope. PMID- 21011726 TI - Decomposition of tartrates by some common fungi. PMID- 21011727 TI - Assay of Streptomycin by the paper-disc plate method. PMID- 21011728 TI - Sources of amylase-producing bacteria. PMID- 21011729 TI - The nonreliability of the benzidine blood reaction for the detection of Clostridium parabotulinum. PMID- 21011731 TI - A new sterile technique for preparing agar cup plates. PMID- 21011730 TI - Studies on the nature of the thermophilic fermentation of cellulose; oxygen relations. PMID- 21011732 TI - [Not Available]. PMID- 21011733 TI - [Not Available]. PMID- 21011734 TI - [Not Available]. PMID- 21011735 TI - [Not Available]. PMID- 21011736 TI - [Not Available]. PMID- 21011737 TI - [Not Available]. PMID- 21011738 TI - [Not Available]. PMID- 21011739 TI - SPREAD of tuberculosis within families in the United States and in a tropical country (Jamaica, B.W.I.). PMID- 21011740 TI - On the mechanism of heterosis; metabolic capacity of different races of Drosophila melanogaster for egg production. PMID- 21011741 TI - On the causes of mosaicism associated with heterochromatic chromosome regions. PMID- 21011742 TI - The constants in the logistic equation. PMID- 21011743 TI - Interspecific hybridization in Stipa L.; natural hybrids. PMID- 21011744 TI - [Not Available]. PMID- 21011745 TI - [Not Available]. PMID- 21011746 TI - [Not Available]. PMID- 21011747 TI - [Not Available]. PMID- 21011748 TI - [Not Available]. PMID- 21011749 TI - [Not Available]. PMID- 21011750 TI - [Not Available]. PMID- 21011751 TI - [Not Available]. PMID- 21011752 TI - [Not Available]. PMID- 21011753 TI - [Not Available]. PMID- 21011754 TI - A note on the rate of morphogenetic movement in the slime mold, Dictyostelium discoideum. PMID- 21011755 TI - Graduation of human growth curves. PMID- 21011756 TI - Relative growth in races of mice produced by selection. PMID- 21011757 TI - The rate of growth of tadpoles in varying concentrations of Ringer's solution. PMID- 21011758 TI - Prepubertal castration in the male chimpanzee, with some effects of replacement therapy. PMID- 21011759 TI - Tolerance of larvae of Drosophila for amino acids; tyrosine, phenylalanine, and alanine. PMID- 21011760 TI - Integrated programs for growth symposia. PMID- 21011761 TI - [Not Available]. PMID- 21011762 TI - Negative displacement of the RS-T segment in the electrocardiogram and its relationship to positive displacement; an experimental study. PMID- 21011763 TI - [Not Available]. PMID- 21011764 TI - Rheumatic fever and heart disease follow-up studies. PMID- 21011765 TI - [Not Available]. PMID- 21011766 TI - [Not Available]. PMID- 21011767 TI - The theory of certain analytical procedures, with particular reference to micro biological assays. PMID- 21011768 TI - The determination of carotene and vitamin A in butter and margarine. PMID- 21011769 TI - A photoelectric photometer for the estimation of vitamin A in margarine. PMID- 21011770 TI - The composition of commercial methylene blue. PMID- 21011771 TI - The separation and determination of lead as iodate and its application to glass analysis. PMID- 21011772 TI - A new method for the absorptiometric determination of chromium in low alloy steels by oxidation with potassium bromate. PMID- 21011773 TI - A works test for excess lime in water treatment. PMID- 21011774 TI - A dentofacial study of male students at the University of Michigan in the physical hardening program. PMID- 21011775 TI - The expansion bar appliance. PMID- 21011776 TI - Investigations of neuropathologic manifestations of oral tissues; a preliminary report. PMID- 21011778 TI - Oral manifestation in Von Recklinghausen's disease (neurofibromatosis); with a case report. PMID- 21011777 TI - Extreme lateral excursion of the mandible simulating dislocation; case report. PMID- 21011779 TI - Surgery of the mandible; the ameloblastoma. PMID- 21011780 TI - A treatise on harelip and cleft plate. PMID- 21011781 TI - Oxygen-want in general anesthesia. PMID- 21011782 TI - Appliances to correct resected or missing portions of the mandible. PMID- 21011783 TI - Treatment of 1,000 jaw fractures. PMID- 21011784 TI - The London dentist of the 17th Century. PMID- 21011785 TI - The Japanese invasion of Malaya and the Dental School, Singapore. PMID- 21011786 TI - Auto analgesia for conservative dental treatment. PMID- 21011787 TI - Notes on prosthetic procedures. PMID- 21011788 TI - Dental disease in relation to skin disease. PMID- 21011789 TI - Vitamins and the mouth. PMID- 21011790 TI - Practical full denture prosthesis. PMID- 21011792 TI - Reminiscences of the early days of the American College of Dentists. PMID- 21011791 TI - American College of Dentists; 25th anniversary. PMID- 21011793 TI - Organization, ideals and achievements of the American College of Dentists. PMID- 21011794 TI - The discovery of the primary dentition; Gabriele Fallopio; an annotated translation. PMID- 21011795 TI - Effect of estrone on tooth buds and bones in growing dogs. PMID- 21011796 TI - Dental school libraries as teaching agencies. PMID- 21011797 TI - The means employed to interest teachers and students in the use of the dental library. PMID- 21011798 TI - The library, an adjunct to teaching. PMID- 21011800 TI - The work of the dental teacher. PMID- 21011799 TI - The library, an adjunct to teaching. PMID- 21011801 TI - Physiology of the oral tissues in health and disease. PMID- 21011802 TI - Penicillin lozenges in the treatment of oral lesions (a continuation report). PMID- 21011804 TI - A simple radiodontic technique. PMID- 21011803 TI - The relation of ascorbic acid intake to gingivitis. PMID- 21011805 TI - [Not Available]. PMID- 21011806 TI - The effect of 2-methyl-1,4-naphthoquinone on the incidence of dental caries. PMID- 21011807 TI - The effect of prolonged ingestion of synthetic vitamin K in rats. PMID- 21011808 TI - A test of the effect of fluoride-containing dentifrices on dental caries. PMID- 21011809 TI - Observation of increased caries activity following interruption of topical fluorine applications. PMID- 21011810 TI - Salivary dilution of 1-1000 sodium fluoride solution used as a mouthwash. PMID- 21011811 TI - The isolation of Candida albicans from a root canal undergoing penicillin therapy. PMID- 21011812 TI - Physiological significance of phospholipid in human salvia. PMID- 21011813 TI - The treatment of maxillo-facial injuries in the field. PMID- 21011814 TI - Treatment of maxillo-facial cases at casualty clearing station. PMID- 21011815 TI - The manipulation of filling materials. PMID- 21011816 TI - Supplement to a plan to provide a national dental service. PMID- 21011817 TI - Mouth conditions in some systematic conditions. PMID- 21011818 TI - Measuring edentulous patients for suitable teeth. PMID- 21011819 TI - An unorthodox filling material. PMID- 21011820 TI - Intra-osseous local anaesthesia. PMID- 21011821 TI - Oldest hospital in the Western Hemisphere. PMID- 21011823 TI - Rapidanalysis; a new analytical technique. PMID- 21011822 TI - NONSPECIFIC reactions in routine blood testing for syphilis. PMID- 21011824 TI - Recovery from botulism coma following ultraviolet blood irradiation. PMID- 21011825 TI - Evaluation of gastroscopic, roentgen, sigmoidoscopic and laboratory procedures in 500 gastrointestinal cases. PMID- 21011826 TI - Perforation of the esophagus caused by flexible gastroscope; a case report. PMID- 21011827 TI - Gastroscopy. PMID- 21011828 TI - Tuberculosis of the stomach. PMID- 21011829 TI - [Not Available]. PMID- 21011830 TI - [Not Available]. PMID- 21011831 TI - [Not Available]. PMID- 21011832 TI - [Not Available]. PMID- 21011833 TI - [Not Available]. PMID- 21011835 TI - [Not Available]. PMID- 21011834 TI - [Not Available]. PMID- 21011836 TI - [Not Available]. PMID- 21011837 TI - [Not Available]. PMID- 21011838 TI - [Not Available]. PMID- 21011839 TI - The relation between eye-colour and defective colour-vision. PMID- 21011840 TI - Sex education aims, possibilities and plans. PMID- 21011841 TI - Gregory King and the population of England and Wales at the end of the seventeenth century. PMID- 21011842 TI - The nonsurgical treatment of sciatica. PMID- 21011843 TI - Reiter's disease with cutaneous lesions resembling keratodermia blenorhagica. PMID- 21011844 TI - The construction of medical manikins for teaching purposes. PMID- 21011845 TI - The structural shoulder problem in general practice. PMID- 21011846 TI - Reflexes due to anorectal disease. PMID- 21011847 TI - Management of the common cold and acute sinusitis. PMID- 21011848 TI - Are you sure it is labor? PMID- 21011849 TI - What is the future role of hospitals in nursing education? PMID- 21011850 TI - MODERN standards in adequate facilities for obstetric care. PMID- 21011851 TI - The camera has a place in a hospital's teaching program. PMID- 21011852 TI - The well organized formulary serves the convenience of all. PMID- 21011853 TI - Poverty is not the sole guide in liability for care. PMID- 21011854 TI - The modern health center; designed for regions of mild climate. PMID- 21011855 TI - The psychiatric hospital plays a part in public health. PMID- 21011856 TI - Merit evaluation. PMID- 21011857 TI - Recent developments in occupational therapy. PMID- 21011858 TI - Blue Cross goes to towns. PMID- 21011860 TI - New methods for point by point calculations. PMID- 21011859 TI - Brightness control in a model schoolroom. PMID- 21011861 TI - Ascaris lumbricoides; a review of its most important facts. PMID- 21011862 TI - The surgical complications of ascariasis. PMID- 21011863 TI - Ascariasis of the duodenal bulb; with three case reports. PMID- 21011864 TI - The pharmacological basis of anthelmintics in ascaris therapy. PMID- 21011865 TI - Post-arsphenamin jaundice in pregnancy. PMID- 21011866 TI - Post-hepatitic hypoglycaemia. PMID- 21011867 TI - Post-hepatitic hypoglycaemia and hyperfunctioning stomach. PMID- 21011868 TI - Problems of sterility. PMID- 21011869 TI - A simple scheme for the spectroscopical identification of blood pigments. PMID- 21011870 TI - Some prenatal causes of congenital eye anomalies. PMID- 21011871 TI - Pain after amputation; simple stump pain; phantome sensation; causalgia. PMID- 21011872 TI - [Not Available]. PMID- 21011873 TI - [Not Available]. PMID- 21011874 TI - [Not Available]. PMID- 21011875 TI - [Not Available]. PMID- 21011876 TI - [Not Available]. PMID- 21011877 TI - [Not Available]. PMID- 21011878 TI - Acute myocarditis in mumps (epidemic parotitis). PMID- 21011879 TI - Pneumothorax in young adult males; descriptive statistics in one hundred and twenty-six cases. PMID- 21011880 TI - Streptomycin for certain systemic infections and its effect on the urinary and fecal flora. PMID- 21011881 TI - Hemolytic streptococcus sore throat; detailed study of the simultaneous infection of a large number of men by a single type. PMID- 21011882 TI - Small adenomas of the adrenal cortex in hypertension and diabetes. PMID- 21011883 TI - Paroxysmal hemoglobinuria due to the cold hemolysin; observations with a report of a case of its occurence in an aerial gunner. PMID- 21011884 TI - Congenital idiopathic methemoglobinemia; favorable response to ascorbic acid therapy. PMID- 21011885 TI - Study of water and heat loss from the respiratory tract of man; methods: a gravimetric method for the measurement of the rate of water loss; a quantitative method for the measurement of the rate of heat loss. PMID- 21011886 TI - Rate of water and heat loss from the respiratory tract of normal subjects in a subtropical climate. PMID- 21011887 TI - Some observations on primary atypical pneumonia. PMID- 21011888 TI - Acute porphyria; clinical and pathologic observations. PMID- 21011889 TI - Relation of nutritional deficiency to cardiac dysfunction. PMID- 21011890 TI - Extragenital chorionepithelioma in the male. PMID- 21011891 TI - Plasma quinacrine concentration in treatment of Plasmodium vivax malaria acquired in the South Pacific. PMID- 21011892 TI - Social medicine. PMID- 21011893 TI - Irregular haemagglutinins after transfusion. PMID- 21011894 TI - Clinical diagnosis of lumbar intervertebral disk protrusions; with indications for their operative removal. PMID- 21011895 TI - Surgical treatment of dysenteric lesions of the bowel among allied prisoners of war in Burma and Thailand. PMID- 21011896 TI - Streptococcal military infiltration of the lungs, with description of a case. PMID- 21011897 TI - Hereditary clubbing of digits in two families. PMID- 21011898 TI - Leiomyoma of the ileum producing intussusception. PMID- 21011899 TI - Medical experiences in Siam. PMID- 21011900 TI - Lymphangitis mesenterialis. PMID- 21011901 TI - Psychological reactions in soldiers to the loss of vision of one eye, and their treatment. PMID- 21011902 TI - Occurrence of a flagellate in the sputum of a case of bronchiectasis. PMID- 21011903 TI - Abacterial pyuria. PMID- 21011904 TI - Two cases of amoebic granuloma. PMID- 21011905 TI - Crush syndrome and plasma jaundice in pregnancy. PMID- 21011906 TI - Bacteriology of septic fingers. PMID- 21011907 TI - Repair of femoral artery after a bullet wound. PMID- 21011908 TI - PRINCIPLE and unity. PMID- 21011909 TI - Premedical zoology; a different view-point. PMID- 21011910 TI - PUERPERAL bacteriaemia and septicaemia. PMID- 21011911 TI - Paralytic ileus. PMID- 21011912 TI - Homosexuality. PMID- 21011913 TI - [Not Available]. PMID- 21011914 TI - [Not Available]. PMID- 21011915 TI - [Not Available]. PMID- 21011916 TI - [Not Available]. PMID- 21011917 TI - [Not Available]. PMID- 21011918 TI - [Not Available]. PMID- 21011919 TI - [Not Available]. PMID- 21011920 TI - [Not Available]. PMID- 21011922 TI - [Not Available]. PMID- 21011923 TI - [Not Available]. PMID- 21011921 TI - [Not Available]. PMID- 21011924 TI - HISTORY of the Vancouver Medical Association. PMID- 21011925 TI - The treatment of defects of the long bones by cancellous chip bone grafts. PMID- 21011926 TI - Protruded intervertebral disc; a report on 60 operative cases. PMID- 21011927 TI - Focal sepsis; with special reference to teeth. PMID- 21011928 TI - Occurrence of natural malaria in very young infants. PMID- 21011929 TI - The progress of malaria control measures in Trinidad and Tobago with special references to County St. David. PMID- 21011930 TI - Tubercle endotoxoid in pulmonary tuberculosis. PMID- 21011931 TI - A case of stinkblaar (Datura stramonium L.) poisoning associated with hyperpyrexia. PMID- 21011932 TI - The value of preliminary caecostomy in the treatment of gastrojejunocolic fistula. PMID- 21011933 TI - Clinical review; allergy. PMID- 21011934 TI - Observations on a case of orbital varix. PMID- 21011935 TI - Familial idiopathic methaemoglobinaemia and its treatment with ascorbic acid. PMID- 21011936 TI - Experimental limb ischaemia in man with especial reference to the role of adenosine triphosphate. PMID- 21011937 TI - Development and course of exophthalmos and ophthalmoplegia in Graves' disease with special reference to the effect of thyroidectomy. PMID- 21011938 TI - Thrombosis of the femoral artery with myohaemoglobinuria and low serum potassium concentration. PMID- 21011939 TI - The nature of the circulatory changes in burn shock. PMID- 21011940 TI - The role of the kidney in acute and chronic hypertension following renal artery constriction in the rabbit. PMID- 21011941 TI - Heart failure and bone blood flow in osteitis deformans. PMID- 21011942 TI - Congenital tricuspid stenosis. PMID- 21011943 TI - Angina pectoris and tobacco. PMID- 21011944 TI - Haemoglobin levels in blood donors. PMID- 21011945 TI - The Ehlers-Danlos syndrome; a description of three cases. PMID- 21011946 TI - Two cases of neo-natal tuberculosis. PMID- 21011947 TI - The detection and treatment of nutritive failure. PMID- 21011948 TI - Treatment of heart failure. PMID- 21011949 TI - Laboratory tests in gastroenterological diagnosis. PMID- 21011950 TI - Psychiatry in medicine. PMID- 21011951 TI - Malpositions of uterus. PMID- 21011952 TI - The treatment of epilepsy in children. PMID- 21011953 TI - Physical therapy in rheumatic conditions. PMID- 21011954 TI - Historical development of the prescription. PMID- 21011956 TI - The injection treatment of esophageal varices. PMID- 21011955 TI - Artificial respiration. PMID- 21011957 TI - Venous thromboembolic disease. PMID- 21011958 TI - Streptomycin treatment of tularemia. PMID- 21011959 TI - Dicumarol in acute coronary thrombosis. PMID- 21011960 TI - New opportunities for physicians in the Veterans Administration. PMID- 21011961 TI - Hypoglycemia due to insular adenoma of pancreas. PMID- 21011962 TI - What is orthoptics? PMID- 21011963 TI - Medical service for veterans. PMID- 21011964 TI - MALPRACTICE; uterine tumor mistaken for pregnancy [Nebraska, 1944]. PMID- 21011965 TI - The psychosomatic matrix. PMID- 21011966 TI - Combined placenta praevia and abrupto placentae; report of case. PMID- 21011967 TI - Thrombophlebitis, experience at an Army general hospital. PMID- 21011968 TI - Empirical treatment of metastatic carcinoma; a case report. PMID- 21011969 TI - Maxillofacial injuries. PMID- 21011970 TI - Modern psychiatric treatment. PMID- 21011971 TI - Influenza virus vaccine, types A and B, for general use. PMID- 21011972 TI - Hydrolysates, the answer to the problem of nutrition. PMID- 21011973 TI - Anterior poliomyelitis, a complication of influenza. PMID- 21011974 TI - Report on activity of Committee on Rural Medical Service of the American Medical Association. PMID- 21011975 TI - Primary carcinoma of the ileum; case report. PMID- 21011976 TI - Submucous lipoma of the jejunum; report of a case. PMID- 21011977 TI - Postoperative bacterial synergistic gangrene cured with penicillin. PMID- 21011978 TI - A consideration of the patient and his disease; five case reports. PMID- 21011979 TI - Intravenous fluids. PMID- 21011980 TI - Thiouracil. PMID- 21011981 TI - The clinical use of diuretics. PMID- 21011982 TI - IMPACT of the war on the Health Department. PMID- 21011983 TI - Tourist camps. PMID- 21011984 TI - [Not Available]. PMID- 21011985 TI - [Not Available]. PMID- 21011986 TI - Vitamin K, its discovery, biochemistry and application in medicine. PMID- 21011987 TI - The visceral manifestations of Kaposi's sarcoma. PMID- 21011988 TI - Effect of weight reduction on course of arterial hypertension. PMID- 21011989 TI - Cancer of the lung in the presence of pulmonary tuberculosis. PMID- 21011990 TI - Anterior mediastinal neoplasm with unusual x-ray appearance. PMID- 21011991 TI - Cylindroma of bronchus; pneumonectomy; peripheral carcinoma of lung; lobectomy and chest wall resection. PMID- 21011992 TI - Essays on the biology of disease; arteriosclerosis. PMID- 21011993 TI - Chest injuries. PMID- 21011995 TI - Recent trends in orthopedic surgery. PMID- 21011994 TI - Acute infectious hepatitis. PMID- 21011996 TI - Undulant fever. PMID- 21011997 TI - Varicose veins. PMID- 21011998 TI - The care of the aged; observations based on experience in Glasgow outdoor medical service. PMID- 21011999 TI - Dust in surgical theatres as a possible source of postoperative tetanus. PMID- 21012000 TI - Determination of blood-groups; use of rabbit immune serum. PMID- 21012001 TI - Hippuric-acid synthesis test of liver function; some difficulties in interpretation. PMID- 21012002 TI - Comparative value of tuberculin tests. PMID- 21012003 TI - Social ecology of the Radstock coalfield. PMID- 21012004 TI - Effect of large doses of alkali on kidney function. PMID- 21012005 TI - The running ear. PMID- 21012006 TI - Pneumonia. PMID- 21012008 TI - Tradition, finance and the future of medicine. PMID- 21012007 TI - Tuberculosis. PMID- 21012011 TI - Accuracy of hemoglobin determinations on finger-tip blood. PMID- 21012009 TI - Varicose veins. PMID- 21012010 TI - Tuberculosis; the problem of its cure and prevention. PMID- 21012013 TI - An instrument for measurement of vibration sensation in man. PMID- 21012012 TI - Vibration sense and fatigue. PMID- 21012014 TI - Social and psychological factors affecting fertility; the sampling plan, selection, and the representativeness of couples in the inflated sample. PMID- 21012017 TI - Some unusual aspects of tularemia as found in Mississippi. PMID- 21012015 TI - Medical education for the laity. PMID- 21012016 TI - The management of varicose veins and their complications. PMID- 21012018 TI - A tickborne epidemic of tularemia. PMID- 21012019 TI - Penicillin in the treatment of bronchiectasis; a preliminary report. PMID- 21012020 TI - The clinical aspects of rheumatic fever in adults. PMID- 21012021 TI - Ainhum. PMID- 21012022 TI - Foreign programs of medical care and their lessons. PMID- 21012023 TI - Carcinoma of the cervix; an attempted follow-up study of 500 cases; the responsibility of the medical profession for the end-results. PMID- 21012024 TI - Lipocaic in the treatment of non-tropical sprue; report of a case. PMID- 21012025 TI - Schistosomiasis (Manson's); presentation of twenty-five cases. PMID- 21012027 TI - Infection; an etiologic factor in diabetes mellitus. PMID- 21012026 TI - Multiple common bile duct stones; report of a case with twenty-six oxalate stones in the common duct. PMID- 21012028 TI - Pathology of Boeck's sarcoid. PMID- 21012029 TI - Extra-intestinal amebiasis and its diagnosis. PMID- 21012030 TI - Hepatic abscess secondary to perforated duodenal ulcer. PMID- 21012031 TI - Primary carcinoma of the liver in infants and children. PMID- 21012032 TI - Results of four years of tuberculosis screening. PMID- 21012033 TI - Short P-R interval syndrome. PMID- 21012034 TI - Symptoms developed in workers cutting and welding galvanized iron. PMID- 21012035 TI - The problem of footwear. PMID- 21012036 TI - Congenital abnormalities of the foot. PMID- 21012037 TI - Minor surgery of the foot. PMID- 21012039 TI - Indications for chiropody. PMID- 21012038 TI - Skin diseases of the foot. PMID- 21012040 TI - Defective speech in children. PMID- 21012041 TI - Surgery in old age. PMID- 21012042 TI - The treatment of penile warts (condylomata acuminata) with podophyllin. PMID- 21012043 TI - Respiratory disease. PMID- 21012044 TI - Penicillin. PMID- 21012045 TI - The use of digitalis. PMID- 21012046 TI - [Not Available]. PMID- 21012047 TI - [Not Available]. PMID- 21012048 TI - [Not Available]. PMID- 21012049 TI - [Not Available]. PMID- 21012050 TI - [Not Available]. PMID- 21012051 TI - [Not Available]. PMID- 21012052 TI - [Not Available]. PMID- 21012053 TI - [Not Available]. PMID- 21012054 TI - [Not Available]. PMID- 21012055 TI - [Not Available]. PMID- 21012056 TI - [Not Available]. PMID- 21012057 TI - [Not Available]. PMID- 21012058 TI - [Not Available]. PMID- 21012059 TI - [Not Available]. PMID- 21012060 TI - [Not Available]. PMID- 21012061 TI - [Not Available]. PMID- 21012062 TI - [Not Available]. PMID- 21012063 TI - [Not Available]. PMID- 21012064 TI - [Not Available]. PMID- 21012065 TI - [Not Available]. PMID- 21012066 TI - [Not Available]. PMID- 21012067 TI - [Not Available]. PMID- 21012068 TI - [Not Available]. PMID- 21012069 TI - [Not Available]. PMID- 21012070 TI - [Not Available]. PMID- 21012071 TI - [Not Available]. PMID- 21012072 TI - [Not Available]. PMID- 21012073 TI - [Not Available]. PMID- 21012074 TI - [Not Available]. PMID- 21012075 TI - [Not Available]. PMID- 21012076 TI - [Not Available]. PMID- 21012077 TI - [Not Available]. PMID- 21012078 TI - [Not Available]. PMID- 21012079 TI - [Not Available]. PMID- 21012080 TI - [Not Available]. PMID- 21012081 TI - [Not Available]. PMID- 21012082 TI - [Not Available]. PMID- 21012083 TI - [Not Available]. PMID- 21012085 TI - [Not Available]. PMID- 21012086 TI - [Not Available]. PMID- 21012084 TI - [Not Available]. PMID- 21012087 TI - [Not Available]. PMID- 21012088 TI - [Not Available]. PMID- 21012089 TI - [Not Available]. PMID- 21012090 TI - [Not Available]. PMID- 21012091 TI - [Not Available]. PMID- 21012092 TI - [Not Available]. PMID- 21012093 TI - [Not Available]. PMID- 21012094 TI - [Not Available]. PMID- 21012095 TI - [Not Available]. PMID- 21012097 TI - [Not Available]. PMID- 21012096 TI - [Not Available]. PMID- 21012098 TI - [Not Available]. PMID- 21012099 TI - [Not Available]. PMID- 21012100 TI - [Not Available]. PMID- 21012101 TI - [Not Available]. PMID- 21012102 TI - [Not Available]. PMID- 21012103 TI - [Not Available]. PMID- 21012104 TI - [Not Available]. PMID- 21012105 TI - [Not Available]. PMID- 21012106 TI - [Not Available]. PMID- 21012107 TI - [Not Available]. PMID- 21012108 TI - [Not Available]. PMID- 21012109 TI - [Not Available]. PMID- 21012110 TI - [Not Available]. PMID- 21012112 TI - [Not Available]. PMID- 21012111 TI - [Not Available]. PMID- 21012113 TI - [Not Available]. PMID- 21012114 TI - [Not Available]. PMID- 21012115 TI - [Not Available]. PMID- 21012116 TI - [Not Available]. PMID- 21012117 TI - [Not Available]. PMID- 21012118 TI - [Not Available]. PMID- 21012119 TI - [Not Available]. PMID- 21012120 TI - [Not Available]. PMID- 21012121 TI - [Not Available]. PMID- 21012122 TI - [Not Available]. PMID- 21012123 TI - [Not Available]. PMID- 21012124 TI - [Not Available]. PMID- 21012125 TI - [Not Available]. PMID- 21012126 TI - [Not Available]. PMID- 21012128 TI - [Not Available]. PMID- 21012127 TI - [Not Available]. PMID- 21012129 TI - [Not Available]. PMID- 21012130 TI - [Not Available]. PMID- 21012131 TI - [Not Available]. PMID- 21012132 TI - [Not Available]. PMID- 21012133 TI - [Not Available]. PMID- 21012134 TI - [Not Available]. PMID- 21012135 TI - [Not Available]. PMID- 21012136 TI - [Not Available]. PMID- 21012137 TI - [Not Available]. PMID- 21012138 TI - [Not Available]. PMID- 21012140 TI - [Not Available]. PMID- 21012139 TI - [Not Available]. PMID- 21012141 TI - [Not Available]. PMID- 21012142 TI - [Not Available]. PMID- 21012143 TI - [Not Available]. PMID- 21012144 TI - [Not Available]. PMID- 21012145 TI - [Not Available]. PMID- 21012147 TI - Multiple transfusions. PMID- 21012146 TI - [Not Available]. PMID- 21012148 TI - Manifestations of diseases in the mouth. PMID- 21012149 TI - The medico-dental relationship. PMID- 21012150 TI - Surgery in Rhode Island. PMID- 21012151 TI - Community needs and the hospital future. PMID- 21012152 TI - Prepaid hospital insurance. PMID- 21012154 TI - Acute haemolytic anaemia of unknown origin. PMID- 21012153 TI - Epidural anaesthesia. PMID- 21012155 TI - Women in medicine; the past. PMID- 21012156 TI - Women in medicine; the present. PMID- 21012157 TI - The patient's history in diagnosis. PMID- 21012158 TI - Torula infection of the central nervous system: four recent cases. PMID- 21012159 TI - Medical research in physical education; impetigo scabies and cutaneous manifestations of malnutrition. PMID- 21012160 TI - Penicillin in dental and oral surgery. PMID- 21012161 TI - Is prostatitis respectable? PMID- 21012162 TI - The history of the O.R.C. Medical Society. PMID- 21012164 TI - Diagnosis and management of gallbladder disease. PMID- 21012163 TI - Urticaria; with observations on the use of the new anti-histamine drug, benadryl. PMID- 21012165 TI - SOCIALIZE everything or nothing. PMID- 21012166 TI - Nephrotic edema in diabetes mellitus. PMID- 21012167 TI - Cytological study of nipple secretions; an aid in the diagnosis of breast lesions. PMID- 21012169 TI - Causes of economic blindness in Texas; a statistical survey of 6,106 cases, aid to the blind program, Texas State Department of Public Welfare. PMID- 21012168 TI - Coarctation of the aorta, patent ductus arteriosus and interventricular septal defect; report of a case. PMID- 21012170 TI - Maternal overprotection in young children. PMID- 21012171 TI - A clinical and pathological study of 170 ovarian tumors. PMID- 21012172 TI - The Tom Green County Tuberculosis Association program. PMID- 21012173 TI - Liver biopsy; clinical evaluation of a trephine needle. PMID- 21012174 TI - Treatment of prostatic carcinoma by castration and by administration of estrogenic hormone; a second report on comparison. PMID- 21012175 TI - The clinical use of antibiotics. PMID- 21012176 TI - Tuberculosis meningitis; a case report. PMID- 21012177 TI - Seven-year report from Neuropsychiatric Department, Student Health Service, University of Wisconsin. PMID- 21012178 TI - An evaluation of the present status of thiouracil therapy in thyrotoxicosis and a report of its use in 22 cases. PMID- 21012179 TI - Shock in forward areas. PMID- 21012181 TI - CANCER detection centers. PMID- 21012180 TI - Blood transfusion malaria in the post-war period. PMID- 21012182 TI - The amateur in medical history. PMID- 21012183 TI - The effects of calcium chloride and of calcium lactate administered by gavage. PMID- 21012184 TI - Genetic analysis of the induction of tumors by methylcholanthrene; the effects of selection toward resistance. PMID- 21012185 TI - Pharmacological acitvity of basic alkyl esters of substituted pyrrolidine dicarboxylic acids; local anesthetic activity and toxicity. PMID- 21012186 TI - Local anesthetic activity and toxicity of di-(beta-diethylaminoethyl) ester of 1 benzyl 2,5- dicarboxy pyrrolidine. PMID- 21012187 TI - Pharmacological activity of basic alkyl esters of substituted pyrrolidine dicarboxylic acids; action on intestine, uterus, and blood pressure. PMID- 21012188 TI - Taxonomic studies on the enterococci. PMID- 21012189 TI - Delayed diagnosis in tubal abortion; a report of two cases. PMID- 21012190 TI - Streptomycin in tuberculous meningitis; a report of its use in a one-year-old infant. PMID- 21012191 TI - The toxicology of arsenic. PMID- 21012192 TI - Microfilm for the scientist and scholar. PMID- 21012193 TI - Light absorption and chemical structure. PMID- 21012194 TI - The calculation of the calorific value of foods. PMID- 21012195 TI - Food yeast, its importance and manufacture. PMID- 21012196 TI - Studies in the constituents of chana (Cicer arie tinum Linn.); the constitution of ciochanin A. PMID- 21012197 TI - Preparation of activated charcoal (medicinal). PMID- 21012198 TI - Anti-corrosive action of the oxalic acid series. PMID- 21012199 TI - Manufacture of potassium chlorate. PMID- 21012200 TI - The iodine content of the thyroid glands of sharks. PMID- 21012201 TI - Fifty years of atomic physics. PMID- 21012202 TI - Health protection activities of the plutonium project. PMID- 21012203 TI - Resonance reactions. PMID- 21012204 TI - Methods and objectives in the separation of isotopes. PMID- 21012205 TI - Problems and prospects in elementary particle research. PMID- 21012206 TI - Social adjustments to atomic energy. PMID- 21012207 TI - The implications of the atomic bomb for international relations. PMID- 21012208 TI - The control of atomic energy under the Charter. PMID- 21012209 TI - World control of atomic energy. PMID- 21012210 TI - Atomic energy as a human asset. PMID- 21012211 TI - Production of particle energies beyond 200 Mev. PMID- 21012212 TI - A modified Kelvin method for measuring contact potential differences. PMID- 21012213 TI - A jet viscometer with variable rate of shear. PMID- 21012214 TI - A high speed microtome for the electron microscope. PMID- 21012215 TI - Counters for use in nuclear spectroscopy. PMID- 21012216 TI - A metal packless vacuum valve. PMID- 21012217 TI - Use of 6AK5 and 954 tubes in ionization chamber pulse amplifiers. PMID- 21012218 TI - Sterility induced in growing rats on a tryptophane deficient diet. PMID- 21012219 TI - Notes on the possibility of a histochemical method for localizing adenosinetriphosphatase. PMID- 21012220 TI - A simple automatic pressure-regulating device for use with vacuum lines. PMID- 21012221 TI - Blood group factors and racial relationships. PMID- 21012222 TI - Uniform luminescent materials. PMID- 21012223 TI - Characterization of pectin. PMID- 21012225 TI - Pulsating perfusing apparatus. PMID- 21012224 TI - Inhibition of growth of Mycobacterium tuberculosis by a mold product; the effect on pathogenic human tubercle bacilli. PMID- 21012226 TI - An apparatus for determining the respiratory volume of large aquatic birds. PMID- 21012227 TI - A new sterile technic for preparing agar cup-plates. PMID- 21012228 TI - The butter-margarine controversy. PMID- 21012229 TI - Developing food acceptance research. PMID- 21012230 TI - The ratio of carotene to carotenoid pigments in sweet-potato varieties. PMID- 21012231 TI - Amino acid and protein deficiencies as causes of corneal vascularization; a preliminary report. PMID- 21012232 TI - Dehydroascorbic acid in cabbage. PMID- 21012233 TI - Buckwheat as a source of rutin. PMID- 21012234 TI - Thiamine depletion of human subjects on a diet rich in thiamine. PMID- 21012235 TI - Effect of methionine supplements on hepatic injury produced by carbon tetrachloride. PMID- 21012236 TI - Inhibition of oxidation of ascorbic acid by certain vegetable extracts. PMID- 21012237 TI - The use of 2,4-dinitrophenylhydrazine for the determination of ascorbic acid. PMID- 21012238 TI - Glutamine from rye grass. PMID- 21012239 TI - Pancreatic enzymes and liver fat. PMID- 21012240 TI - Remarks on the history of the exclusion principle. PMID- 21012241 TI - The high ascorbic acid content of the West Indian cherry. PMID- 21012242 TI - Diabetes produced by feeding alloxan to cats. PMID- 21012243 TI - Sex hormonal action and chemical constitution. PMID- 21012244 TI - Effect of altitude anoxia in provoking relapse in malaria. PMID- 21012246 TI - TEXT of the new Kilgore-Magnuson bill. PMID- 21012245 TI - The transmissions of Litomosoides carinii, filariid parasite of the cotton rat, by the tropical rat mite, Liponyssus bacoti. PMID- 21012247 TI - Tempo and mode in evolution. PMID- 21012248 TI - The basic psychology of rumor. PMID- 21012249 TI - A study in adolescent imagery. PMID- 21012250 TI - Food habits of adolescents in relation to family, training, and present adjustment. PMID- 21012251 TI - Evacuation and the isolated child; a wartime phenomenon. PMID- 21012252 TI - The psychological effects of war on the family and its individual members. PMID- 21012253 TI - The use of boarding homes in conjunction with a private psychiatric residential school. PMID- 21012255 TI - Psychosomatic study of fifty stuttering children; social, physical and psychiatric findings. PMID- 21012254 TI - Psychiatric program in an agency serving youth. PMID- 21012256 TI - Ozeretzky tests. PMID- 21012257 TI - Analysis of responses on the revised Stanford-Binet. PMID- 21012258 TI - Rorschach study. PMID- 21012259 TI - Finger painting in the psychotherapy of children. PMID- 21012260 TI - The psychosomatic component in problem behavior. PMID- 21012261 TI - Dynamic interpretation and treatment of acute stuttering in a young child. PMID- 21012262 TI - Behavior problems of eating. PMID- 21012263 TI - Hygiene and therapy in the nursery and kindergarten. PMID- 21012264 TI - Truancy syndrome. PMID- 21012265 TI - Anticonvulsant activity of sulfoxides and sulfones. PMID- 21012266 TI - Polyopia and monocular diplopia of cerebral origin. PMID- 21012267 TI - The human pyramidal tract; a study of the pyramids in cases of acute and chronic vascular lesions of the brain. PMID- 21012268 TI - Bilateral intracranial section of the glossopharyngeal nerve; report of a case. PMID- 21012269 TI - Multiple sclerosis with late onset of symptoms. PMID- 21012270 TI - Ependymitis and meningitis due to Candida (Monilia) albicans. PMID- 21012271 TI - Narcolepsy; combat experience of a soldier with narcolepsy. PMID- 21012272 TI - Psychopharmacologic study of schizophrenia and depressions; comparison of tolerance to sodium amytal and amphetamine sulfate. PMID- 21012273 TI - Localizing value of vertical nystagmus. PMID- 21012274 TI - Emotional trauma resulting from illegitimate birth. PMID- 21012275 TI - Experimental evidence of the physiologic mechanism of certain types of headache. PMID- 21012276 TI - Unilateral internal ophthalmoplegia; sole clinical sign in patient with syphilitic meningitis. PMID- 21012278 TI - Changes in cerebral veins in hypertensive brain disease and their relation to cerebral hemorrhage; clinical pathologic study. PMID- 21012277 TI - Action of acetylcholine on motor cortex; correlation of effects of acetylcholine and epilepsy. PMID- 21012279 TI - Psychologic studies on a patient who received two hundred and forty-eight shock treatments. PMID- 21012280 TI - Management and treatment of craniocerebral injuries. PMID- 21012281 TI - Psychiatric aspects of injuries to the nervous system. PMID- 21012282 TI - Chronic pain as residual of poliomyelitis of Southern California. PMID- 21012284 TI - Successful treatment of posttraumatic pneumococcic meningitis with large doses of penicillin. PMID- 21012283 TI - Iron encrustation of nerve cells in the vicinity of old traumatic lesions of the cerebral cortex. PMID- 21012285 TI - Intracranial complications of infections of the nasal air passages and accessory sinuses; a further report on the nature and incidence of lesions observed in a series of thirty thousand autopsies. PMID- 21012286 TI - Notes on the pathology of cranial tumors; metastatic tumors of the calvarium with incidental reference to their occurrence in American aborigines. PMID- 21012287 TI - The ancestry of neuropathology; Robert Hooper's Morbid anatomy of the human brain. PMID- 21012288 TI - The palmomental sign. PMID- 21012289 TI - Desire to sing as an aura of epilepsy. PMID- 21012290 TI - Some aspects of epilepsy in the Navy. PMID- 21012291 TI - The use of dilantin in the treatment of psychotic patients unresponsive to other treatment. PMID- 21012292 TI - Psychology of bad influence and good advice. PMID- 21012293 TI - Outline of antisyphilitic treatment in the State hospital. PMID- 21012294 TI - A bacteriologic study of penetrating wounds of the brain, from the surgical point of view. PMID- 21012295 TI - Observations on early type of brain abscess following penetrating wounds of the brain. PMID- 21012296 TI - Eye signs in pineal tumors. PMID- 21012297 TI - Intracranial angiography; the diagnosis of vascular lesions. PMID- 21012298 TI - Hematomas associated with penetrating wounds of the brain. PMID- 21012299 TI - The incidence of interhemispheric extension of glioblastoma multiforme through the corpus callosum. PMID- 21012300 TI - Early complications following penetrating wounds of the skull. PMID- 21012301 TI - The use of curare in the treatment of spastic paralysis. PMID- 21012302 TI - Aneurysm of the internal carotid artery associated with hypothalamic fits. PMID- 21012303 TI - Pineal teratoma; report of case. PMID- 21012304 TI - Technique for pantopaque myelography. PMID- 21012305 TI - Survey of the recent literature on tics in children. PMID- 21012306 TI - Physiologic and differential diagnostic considerations of tic manifestations in children. PMID- 21012307 TI - Observation of children's reactions to motor restraint. PMID- 21012308 TI - Neurodynamics of tics. PMID- 21012309 TI - Hypermotility and transitory tic in a child of seven. PMID- 21012310 TI - Rorschach records of children with a tic syndrome. PMID- 21012311 TI - The parent-child relationships in children afflicted with tics. PMID- 21012312 TI - Psychoterapeutic study of a typical case with tic syndrome. PMID- 21012313 TI - The psychodynamics of the art expression of a boy patient with tic syndrome. PMID- 21012314 TI - The stress tolerance test; preliminary experiments with a new projective technique utilizing both meaningful and meaningless stimuli. PMID- 21012315 TI - A study of conditioned vasomotor responses in ten human subjects. PMID- 21012316 TI - Narcolepsy as a psychogenic symptom. PMID- 21012317 TI - An analysis of the influence of alcohol on experimental neuroses in cats. PMID- 21012318 TI - [Not Available]. PMID- 21012319 TI - [Not Available]. PMID- 21012320 TI - [Not Available]. PMID- 21012321 TI - [Not Available]. PMID- 21012322 TI - [Not Available]. PMID- 21012323 TI - Allergic conditions in infants and children. PMID- 21012324 TI - Intestinal suction. PMID- 21012325 TI - Glaucoma. PMID- 21012326 TI - Day care for a city's children. PMID- 21012328 TI - Hospitals and the nursing profession. PMID- 21012327 TI - Nursing care of casualties in long distance air evacuation. PMID- 21012329 TI - Hemiplegia. PMID- 21012330 TI - Nursing care in hemiplegia. PMID- 21012331 TI - POSTURE fundamentals illustrated; the nurse. PMID- 21012332 TI - Professional nursing; a look into the future. PMID- 21012333 TI - SCHEDULE of minimum entrance salaries for industrial nurses. PMID- 21012334 TI - Industrial nursing goes forward. PMID- 21012335 TI - The prevention of respiratory tract infections in industry. PMID- 21012336 TI - Recent advances in disinfestation; D.D.T. in war and peace. PMID- 21012337 TI - Transplantation of ureters accompanied by total cystectomy. PMID- 21012338 TI - Common skin disorders of children. PMID- 21012339 TI - Midwifery; the service which women can give to women. PMID- 21012340 TI - Two cases of coccydynia. PMID- 21012341 TI - Nursing and physical therapy consultation in State crippled children's programs. PMID- 21012342 TI - Standards in public health nursing. PMID- 21012343 TI - Administering penicillin. PMID- 21012344 TI - PUBLIC health nursing in Sweden. PMID- 21012345 TI - [Not Available]. PMID- 21012346 TI - [Not Available]. PMID- 21012347 TI - [Not Available]. PMID- 21012348 TI - [Not Available]. PMID- 21012349 TI - [Not Available]. PMID- 21012350 TI - [Not Available]. PMID- 21012351 TI - [Not Available]. PMID- 21012352 TI - [Not Available]. PMID- 21012353 TI - [Not Available]. PMID- 21012354 TI - [Not Available]. PMID- 21012355 TI - [Not Available]. PMID- 21012357 TI - [Not Available]. PMID- 21012356 TI - [Not Available]. PMID- 21012358 TI - [Not Available]. PMID- 21012359 TI - Evaluation of stereopsis; a comparison of the Howard-Dolman and the Verhoeff test. PMID- 21012360 TI - The iridencleisis operation for glaucoma. PMID- 21012361 TI - Effect of talc in ocular surgery. PMID- 21012362 TI - Scleral flap incision with scleral sutures for the cataract operation. PMID- 21012363 TI - Law of physiologic aging as derived from long range data on refraction of the human eye. PMID- 21012364 TI - Accommodation of presbyopia and its correction. PMID- 21012365 TI - Removal of the dislocated lens under a conjunctival pocket flap. PMID- 21012366 TI - Foster Kennedy syndrome with post-traumatic arachnoiditis of optic chiasm and base of frontal lobes. PMID- 21012367 TI - Hypertensive retinopathy associated with adrenal medullary tumor (pheochromocytoma). PMID- 21012368 TI - Changes of labyrinthine excitability in lesions of optic tract or external geniculate body. PMID- 21012369 TI - Ocular varicella; report of a case of corneal phlyctenule. PMID- 21012370 TI - Gonioscopy simplified by a contact prism. PMID- 21012371 TI - Development of secretory function of ciliary body in the rabbit eye. PMID- 21012372 TI - Relation of visual acuity to myopia. PMID- 21012373 TI - Melanoma of the skin with intraocular and orbital metastases. PMID- 21012374 TI - Congenital bilateral subluxation of the lens; report of a family. PMID- 21012375 TI - Complications incident to simple intracapsular extraction; some procedures designed toward prevention. PMID- 21012376 TI - Instruments for use in operation for cataract. PMID- 21012378 TI - Blepharoptosis. PMID- 21012377 TI - Keratoconus posticus circumscriptus; report of a case. PMID- 21012379 TI - Ocular sporotrichosis. PMID- 21012380 TI - Efficiency of the lens; a clinical concept. PMID- 21012381 TI - Report on the treatment of myopia by visual training. PMID- 21012382 TI - Orthoptic apparatus. PMID- 21012383 TI - Contact lenses in keratoconus. PMID- 21012384 TI - The first year of the blind rehabilitation program at Dibble General Hospital. PMID- 21012385 TI - Field work services in a residential school for the blind. PMID- 21012386 TI - Home teaching and social case work. PMID- 21012387 TI - USE of radium in the aerotitis control program of the Army Air Forces. PMID- 21012388 TI - Activities of the irradiation clinic at Westover Field, Massachusetts. PMID- 21012389 TI - Report of 52 cases of recurrent aerotitis, First Air Force, Mitchel Field, New York. PMID- 21012390 TI - Report of the Third Air Force Irradiation Unit, 31 August 1945. PMID- 21012391 TI - Aerotitis and radium therapy in the Eighth Air Force. PMID- 21012392 TI - The use of radium in the aerotitis control program in the Twelfth Air Force. PMID- 21012393 TI - Aerotitis program in the Fifteenth Air Force. PMID- 21012394 TI - Some further experiments in the production of negative pressure in the trachea and the frontal sinus by ciliary action. PMID- 21012396 TI - Nasal psychosomatic syndromes accompanying and following acute anxiety. PMID- 21012395 TI - Postnasal drip, the current American nightmare. PMID- 21012397 TI - The use of tantalum in radical frontal sinus surgery. PMID- 21012398 TI - Pneumosinus dilatans. PMID- 21012399 TI - Treatment of suppurative paranasal sinusitis with repeated irrigations of penicillin. PMID- 21012400 TI - Photography through a nasopharyngoscope. PMID- 21012401 TI - Meniere's syndrome; the validity of the intradermal histamine test. PMID- 21012402 TI - Mixed salivary tumor in the right tonsil fossa with narcolepsy and cataplexy. PMID- 21012403 TI - Herpes zoster auris (geniculate ganglionitis). PMID- 21012404 TI - Penicillin therapy in the practice of otolaryngology. PMID- 21012405 TI - Histopathology of the incus and the head of the malleus in cases of stapedial ankylosis. PMID- 21012406 TI - Hyperplastic sinopharyngostomatitis. PMID- 21012407 TI - Prognosis of the recurrent nerve paralysis following thyroidectomy. PMID- 21012409 TI - Stripping of the vocal cords. PMID- 21012408 TI - Treatment of chronic suppurative otitis media with penicillin. PMID- 21012410 TI - The neglected septal cartilage graft, with experimental observations on the growth of human cartilage grafts. PMID- 21012411 TI - Neoplasms of both maxillary sinuses. PMID- 21012412 TI - Atrophic rhinitis and ozena. PMID- 21012413 TI - Occupational deafness, with special reference to chronic occupational deafness. PMID- 21012414 TI - Nonvirulent diphtheria. PMID- 21012415 TI - Deep cellulitis of the face and neck; Ludwig's angina. PMID- 21012416 TI - Thrombosis of a lateral sinus with metastasis; penicillin therapy; recovery. PMID- 21012417 TI - Magnetic aid in inserting an esophageal string. PMID- 21012418 TI - Tumors of the nose and the throat. PMID- 21012420 TI - On correcting the abuse of nose-drops. PMID- 21012419 TI - Tonsils and adenoids. PMID- 21012421 TI - Pitfalls in refraction. PMID- 21012422 TI - An improved procedure for establishing the location of foreign bodies in the alimentary canal. PMID- 21012423 TI - Electrocoagulation in vasomotor rhinitis. PMID- 21012424 TI - [Not Available]. PMID- 21012425 TI - [Not Available]. PMID- 21012426 TI - [Not Available]. PMID- 21012427 TI - Plumbism: punctate basophilia in bone marrow. PMID- 21012428 TI - On the quantitative estimation of prothrombin. PMID- 21012429 TI - Melioidosis. PMID- 21012430 TI - A study of 377 cases of fatal meningitis with special reference to bacteriologic diagnosis. PMID- 21012431 TI - A method of demonstrating anti-Rh agglutinins in cases of erythroblastosis fetalis. PMID- 21012432 TI - Hemolytic disease of the newborn in relation to the Rh factor. PMID- 21012433 TI - The salmonella problem; practical laboratory applications of recent advances. PMID- 21012434 TI - Aneurysm of splenic artery with rupture; case report. PMID- 21012435 TI - Comments by members of Committee on tests for intoxication of National Safety Council on Blood alcohol and intoxication: its value in borderline cases. PMID- 21012436 TI - Answers to comments by members of the Committee on tests for intoxication. PMID- 21012437 TI - The extraction of nitro'genous matter from pollens. PMID- 21012438 TI - Fatigue and weakness of allergic origin (allergic toxemia) to be differentiated from nervous fatigue or neurasthenia. PMID- 21012439 TI - Introduction of allergens into the skin by inunction with intraderm; additional experimental data on the inunction test. PMID- 21012440 TI - Passive transfer of experimental contact dermatitis with the Urbach-Koenigstein technique. PMID- 21012441 TI - Parenteral use of dihydroergotamine in migraine. PMID- 21012442 TI - Successful therapy of a dermatologic syndrome with L. casei factor (folic acid). PMID- 21012443 TI - Sino-bronchial syndrome complicating atopic asthma in children; treatment by roentgen ray. PMID- 21012444 TI - Combined tyrothrycin-penicillin therapy in contact dermatitis. PMID- 21012445 TI - Effects of varying degrees of hypophysectomy in the dog. PMID- 21012446 TI - Relationship of Boeck's sarcoid and tuberculosis. PMID- 21012447 TI - The diverticula (Luschka's crypts) of the gallbladder. PMID- 21012448 TI - Histologic changes in ovary and uterus of live Dirofilaria immitis recovered from dogs treated with trivalent antimony compounds. PMID- 21012449 TI - Renal insufficiency associated with lymphopenia and atrophy of lymphatic tissue in man. PMID- 21012450 TI - Duplication of the vermiform appendix, the large intestine and the urinary bladder; report of a case. PMID- 21012451 TI - Cancer in relation to usages; three new types in India. PMID- 21012452 TI - Experimental nephropathies; a comparison of the toxic action of uranium, mercury and chromium on the kidneys. PMID- 21012453 TI - The bone marrow in folic acid deficiency and its response to crystalline Lactobacillus casei factor (folic acid). PMID- 21012454 TI - Experimental atherosclerosis; the effect of feeding olive oil on the absorption and deposition of cholesterol. PMID- 21012455 TI - Loeffler's syndrome; report of a case with pathologic examination of the lungs. PMID- 21012456 TI - Primary carcinoma of the liver. PMID- 21012458 TI - Carcinoma of the stomach with multiple annular metastatic intestinal infiltrations. PMID- 21012457 TI - Hurthle cell tumor of the thyroid gland in an infant. PMID- 21012459 TI - Intrauterine injection of lysol as an absortifacient; report of a fatal case complicated by oil embolism and lysol poisoning. PMID- 21012460 TI - Papillary carcinoma arising from rete testis. PMID- 21012461 TI - Thrombosis of the gastric coronary vein with spontaneous rupture of the stomach. PMID- 21012462 TI - Cruveilhier-Baumgarten disease; splenomegaly, portal hypertension and patent umbilical vein. PMID- 21012463 TI - Care of the body at autopsy in cooperation with the mortician. PMID- 21012464 TI - Studies on poison ivy and other dermatitis-producing plant parts wherein active, resinous principles are suspended in aqueous solution. PMID- 21012465 TI - A study of the inheritance of respiratory allergies. PMID- 21012466 TI - An allergic reaction following typhus-fever vaccine and yellow-fever vaccine due to egg yolk sensitivity. PMID- 21012467 TI - Anaphylactic shock from skin testing; two cases, one fatal. PMID- 21012468 TI - Bronchial asthma; a critical review. PMID- 21012469 TI - Two cases of mixed malignant tumour of the breast. PMID- 21012470 TI - Malignant tubular adenoma in a horseshoe kidney; its significance with regard to general cancer pathology. PMID- 21012471 TI - A microscopical study of the evolution of mouse mammary cancer; the effect of the milk factor and a comparison with the human disease. PMID- 21012472 TI - The use of the splenectomised rabbit for the assay of liver extracts; with observations on the chemical nature of the antipernicious anaemia factor. PMID- 21012473 TI - Arrhenoblastoma; report of a case with unusual features. PMID- 21012474 TI - The histogenesis of experimental pneumonia in mice. PMID- 21012475 TI - Features in the Congo red molecule associated with the inactivation of complement. PMID- 21012476 TI - The effect of agar depth in the plate method for the assay of penicillin. PMID- 21012477 TI - An experimental approach to the problem of trauma and tumours. PMID- 21012478 TI - A measure of the stimulating effect of simple injury combined with carcinogenic chemicals on tumour formation in mice. PMID- 21012479 TI - Cor biatrium triloculare with transposition of the arterial trunks; a rare congenital cardiac malformation. PMID- 21012480 TI - The virus-neutralising power of serum from recently vaccinated persons. PMID- 21012481 TI - The effect of olivine on the lungs of rats. PMID- 21012482 TI - A comparison of the effects of laevo-rotatory and dextro-rotatory quartz on the lungs of rats. PMID- 21012484 TI - [Not Available]. PMID- 21012483 TI - [Not Available]. PMID- 21012485 TI - [Not Available]. PMID- 21012486 TI - [Not Available]. PMID- 21012487 TI - Antivitamines. PMID- 21012488 TI - [Not Available]. PMID- 21012489 TI - [Not Available]. PMID- 21012490 TI - [Not Available]. PMID- 21012491 TI - [Not Available]. PMID- 21012493 TI - [Not Available]. PMID- 21012492 TI - [Not Available]. PMID- 21012495 TI - [Not Available]. PMID- 21012494 TI - [Not Available]. PMID- 21012496 TI - [Not Available]. PMID- 21012497 TI - [Not Available]. PMID- 21012498 TI - [Not Available]. PMID- 21012499 TI - [Not Available]. PMID- 21012501 TI - [Not Available]. PMID- 21012500 TI - [Not Available]. PMID- 21012502 TI - [Not Available]. PMID- 21012503 TI - [Not Available]. PMID- 21012504 TI - [Not Available]. PMID- 21012505 TI - [Not Available]. PMID- 21012506 TI - [Not Available]. PMID- 21012507 TI - [Not Available]. PMID- 21012508 TI - [Not Available]. PMID- 21012509 TI - [Not Available]. PMID- 21012510 TI - [Not Available]. PMID- 21012511 TI - [Not Available]. PMID- 21012512 TI - [Not Available]. PMID- 21012513 TI - [Not Available]. PMID- 21012514 TI - [Not Available]. PMID- 21012515 TI - Cryptorchidism. PMID- 21012516 TI - Nephrosis. PMID- 21012517 TI - Granulosa-theca cell tumor of the ovary. PMID- 21012518 TI - Epidemic poliomyelitis. PMID- 21012519 TI - Resistance of cotton rats to the virus of poliomyelitis as affected by intake of vitamin A, partial inanition and sex. PMID- 21012520 TI - The use of sulfamerazine in infants and children. PMID- 21012521 TI - The prevention of edema in infants undergoing sulfonamide treatment. PMID- 21012522 TI - Incidence of reactions to sulfonamide drugs in infants and children. PMID- 21012523 TI - Tables for predicting adult height from skeletal age and present height. PMID- 21012524 TI - The use of prostigmine in the management of infantile cerebral paralysis. PMID- 21012525 TI - Cord transfusions in newborn infants; a report of ninety-nine cord transfusions in premature babies, twenty-one in full-term babies and seventy-eight in babies of Rh-negative mothers. PMID- 21012526 TI - Anti Rh agglutinins in the maternal blood without symptoms of hemolytic anemia in the newborn infant. PMID- 21012527 TI - Epidemic meningitis and meningococcemia treated with penicillin. PMID- 21012528 TI - Use of amino acids in a case of severe Salmonella schottmuelleri (paratyphoid B) infection in an infant. PMID- 21012529 TI - Acute gastric ulcer with perforation in one of premature twins; report of a case. PMID- 21012530 TI - Paroxysmal tachycardia; report of two cases in infants. PMID- 21012531 TI - Leiner's disease followed by the celiac syndrome; a case report. PMID- 21012532 TI - The social aspects of medicine. PMID- 21012533 TI - The conservation of hearing in school children. PMID- 21012534 TI - Hearing defects in children; a challenge. PMID- 21012535 TI - Mental health problems in school. PMID- 21012536 TI - [Contribution to the study of sepsis in children]. PMID- 21012538 TI - [On the role of the local hyperergic reaction in the rise of the hemorrhagic syndrome in the large intestine]. PMID- 21012537 TI - [On the daily need of vitamin C in children of nursery age under conditions of the North]. PMID- 21012539 TI - [Prognostical significance of the dynamics of the cerebrospinal fluid in the treatment of meningococcic meningitis]. PMID- 21012540 TI - [Patho-anatomical deformations of the tissues at the site of injection of sulfidine solution (Planelies)]. PMID- 21012541 TI - [On the allergic forms of influenza in infants]. PMID- 21012542 TI - [Connection of enterobiosis in children with fecal soiling of the hands]. PMID- 21012543 TI - [On the method of the treatment of malaria with acriquin in children]. PMID- 21012544 TI - [The questions of the clinics and therapy of pellagra in children]. PMID- 21012545 TI - [Vitamin therapy of affections of the skin and mucous membranes in children]. PMID- 21012546 TI - [Acute fatty necrosis in children]. PMID- 21012547 TI - [Congenital absence of the diaphragm]. PMID- 21012548 TI - [Not Available]. PMID- 21012549 TI - [Not Available]. PMID- 21012550 TI - [Not Available]. PMID- 21012551 TI - BORIC acid intoxication. PMID- 21012552 TI - Topical penicillin. PMID- 21012553 TI - CHEMISTRY of penicillin. PMID- 21012554 TI - Some modern contributions to the enzyme theory of pharmacology. PMID- 21012555 TI - A revised cylinder-plate assay for penicillin. PMID- 21012556 TI - Notes on the water content of crystalline caffeine. PMID- 21012557 TI - Aminoalcohols; p-aminopropadrine. PMID- 21012558 TI - A synthesis of p-aminophenylalanine. PMID- 21012559 TI - Determination of magnesium sulfate and solution of magnesium citrate. PMID- 21012560 TI - Comparative analysis of normal and tetraploid Datura stramonium and Datura tatula. PMID- 21012561 TI - The analgesic properties of some l-acyl-3-aminomethylureas. PMID- 21012562 TI - Iron salts in nutritional anemia. PMID- 21012563 TI - Clinical toxicity of thiouracil. PMID- 21012564 TI - A note on writing prescription labels. PMID- 21012565 TI - Some prospective medical uses of atomic energy. PMID- 21012566 TI - [Not Available]. PMID- 21012567 TI - [Not Available]. PMID- 21012568 TI - [Not Available]. PMID- 21012569 TI - [Not Available]. PMID- 21012570 TI - [Not Available]. PMID- 21012571 TI - [Not Available]. PMID- 21012572 TI - [Not Available]. PMID- 21012573 TI - International biological standards. PMID- 21012574 TI - EFFECT of bombing on health and medical care in Germany. PMID- 21012575 TI - Some experiments on penicillin. PMID- 21012576 TI - CURARE and pentothal. PMID- 21012577 TI - On the thrombopenia of anaphylactic and peptone shock. PMID- 21012578 TI - The role of exercise in altitude pain. PMID- 21012579 TI - The elimination of administered cobalt in pancreatic juice and bile of the dog, as measured with its radioactive isotopes. PMID- 21012580 TI - Potassium deficiency in the rat. PMID- 21012581 TI - Visual thresholds as an index of physiological imbalance during insulin hypoglycemia. PMID- 21012582 TI - Effects of acute hemorrhagic and traumatic shock on renal function of dogs. PMID- 21012583 TI - The renal extraction of oxygen in experimental shock. PMID- 21012584 TI - The effect of oxygen pressure on the uptake of carbon monoxide by man at sea level and at altitude. PMID- 21012585 TI - The relationships between carbon monoxide, oxygen and hemoglobin in the blood of man at altitude. PMID- 21012586 TI - The effect of low concentrations of carboxyhemoglobin on the altitude tolerance of man. PMID- 21012587 TI - Blood sugar levels and carbohydrate administration in human subjects during prolonged exposures to moderately low altitudes. PMID- 21012588 TI - Comparison of renal clearances with direct renal blood flow under control conditions and following renal ischemia. PMID- 21012589 TI - Further observations on induced ovulation in the mouse as a rapid test for pregnancy. PMID- 21012590 TI - The energy cost of horizontal and grade walking on the motor-driven treadmill. PMID- 21012591 TI - The effect of low and high carbohydrate meals on the blood sugar level and on work performance in strenuous exercise of short duration. PMID- 21012592 TI - The effect of diethylstilbestrol on thyroidectomized rats. PMID- 21012593 TI - Effect of compounds related to glycolysis in muscle on the sensitivity of muscle to acetylcholine and potassium. PMID- 21012594 TI - Arterial oxyhemoglobin saturations at critical pressure-altitudes breathing various mixtures of oxygen and nitrogen; with a note on the effect of exercise. PMID- 21012595 TI - The influence of avoidance conditioning on the course of non-avoidance conditioning in dogs. PMID- 21012596 TI - A study of the water losses through the skin in the rat. PMID- 21012597 TI - Venous return in the absence of cardiac drive. PMID- 21012598 TI - Histochemical contributions to physiology. PMID- 21012599 TI - The coronary circulation. PMID- 21012600 TI - Recent experimental studies on leukemia. PMID- 21012601 TI - Neural mechanisms of cutaneous sense. PMID- 21012602 TI - The absorption of triglyceride fat from the intestine. PMID- 21012603 TI - The use of isotopically marked carbon in the study of intermediary metabolism. PMID- 21012604 TI - Yawning and associated phenomena. PMID- 21012605 TI - Mating reactions and conjugation between varieties of Paramecium aurelia in relation to conceptions of mating type and variety. PMID- 21012606 TI - Trophic potentialities of the green flagellate Lobomonas piriformis Pringsheim. PMID- 21012607 TI - Comparisons of mating behavior, growth rate, and factors influencing egg-hatching in South American Haemogogus mosquitoes. PMID- 21012608 TI - Uric acid formation in the developing egg of the grasshopper, Melanoplus differentialis. PMID- 21012609 TI - Modifications of sand-dollar development by exposure to lithium chloride and sodium thiocyanate before and after fertilization. PMID- 21012610 TI - Relation between black and red melanin pigments in feathers. PMID- 21012611 TI - Conditions modifying the expression of silver in the Silver Campine fowl. PMID- 21012612 TI - Protecting the mental health of the veteran. PMID- 21012613 TI - Motion pictures as a medium of education. PMID- 21012614 TI - New evalative methods and future prospects. PMID- 21012615 TI - Psychiatry and the returning veteran. PMID- 21012616 TI - Mentally retarded boys in war time. PMID- 21012617 TI - Music in military medicine. PMID- 21012618 TI - Rehibilitation problems presented by returning service men who seek psychiatric help. PMID- 21012619 TI - Marriage preparation must be modernized. PMID- 21012620 TI - Psychiatric case-work counseling in community centers. PMID- 21012621 TI - Institution or foster home? PMID- 21012622 TI - Psychotherapy and public education. PMID- 21012623 TI - A seminar in psychiatry for theological students. PMID- 21012624 TI - War-time applications of psychology; their value to industry. PMID- 21012625 TI - The economics of vocational selection. PMID- 21012626 TI - Industrial assessments; some problems and suggestions. PMID- 21012627 TI - Psychological facts and psychological theory. PMID- 21012628 TI - Shock therapy; psychologic theory and research. PMID- 21012629 TI - The use of the Wechsler-Bellevue scales; a supplement. PMID- 21012630 TI - Note on Dunlap's remedy for defective color vision. PMID- 21012631 TI - The psychology of attitudes. PMID- 21012632 TI - Psychological testing in military clinical psychology; intelligence testing. PMID- 21012634 TI - The concept of rigidity; a critical evaluation. PMID- 21012633 TI - A stimulus-response analysis of repression and insight in psychotherapy. PMID- 21012635 TI - Howells on the hereditary differential in learning; a criticism. PMID- 21012636 TI - In defense of the Theory of order; a reply to Ivan D. London. PMID- 21012637 TI - Popular responses and cultural differences; an analysis based on frequencies in a group of American Indian subjects. PMID- 21012638 TI - The use of content analysis in Rorschach interpretation; differential characteristics of male homosexuals. PMID- 21012639 TI - Group Rorschach testing in a vocational high school. PMID- 21012640 TI - Experimental psychological diagnosis of mild forms of schizophrenia. PMID- 21012641 TI - The similarity in Rorschach patterns of adult criminal psychopaths and preadolescent boys. PMID- 21012642 TI - The efficacy of group therapy as indicated by group Rorschach records; effect of a convalescent hospital's neuro-psychiatric treatment program on a group of soldiers in an anxiety state. PMID- 21012644 TI - The preparation of slides for measurement of dust particle size. PMID- 21012643 TI - Physical impairments of members of low-income farm families; 11,490 persons in 2,477 Farm Security Administration borrower families, 1940; extent of immunization against smallpox, diptheria, and typhoid fever. PMID- 21012645 TI - Composition of some trade name solvents used for cleaning and degreasing, and for thinning paints. PMID- 21012646 TI - Influence of pH and temperature on the survival of coliforms and enteric pathogens when exposed to chloramine. PMID- 21012647 TI - Diphtheria incidence and trends in relation to artificial immunization with some comparative data for scarlet fever. PMID- 21012648 TI - A new species of Cephalosporium in Madura foot (Cephalosporium granulomatis). PMID- 21012649 TI - A study of the diptheroids found in infectious bovine pyelonephritis. PMID- 21012650 TI - The control of contaminants in penicillin fermentations by antiseptic chemicals. PMID- 21012651 TI - Chemical changes in submerged penicillin fermentations. PMID- 21012652 TI - The effect of certain chemicals on penicillin production and mold metabolism in shake flask fermentations. PMID- 21012653 TI - A method for the rapid preparation of Loffler's and Petroff's media. PMID- 21012654 TI - Some artifacts encountered in stained preparations of tubercle bacilli. PMID- 21012655 TI - A new salmonella type isolated from man, S. orion. PMID- 21012656 TI - Toxicity and antibiotic activity of kojic acid produced by Aspergillus luteovirescens. PMID- 21012657 TI - The identification of Neisseria gonorrhoeae by means of bacterial variation and the detection of small colony forms in clinical material. PMID- 21012658 TI - On the amount of carbon dioxide supplied for the primary isolation of Neisseria gonorrhoeae. PMID- 21012659 TI - The revival of organisms presumably killed by phenol. PMID- 21012660 TI - A remarkable fission yeast, Schizosaccharomyces versatilis nov. sp. PMID- 21012661 TI - The reactions in triple-sugar iron agar produced by paracolon and Proteus bacilli. PMID- 21012662 TI - A study of an epidemic of infantile diarrhea. PMID- 21012663 TI - [Not Available]. PMID- 21012664 TI - [Not Available]. PMID- 21012665 TI - [Not Available]. PMID- 21012666 TI - [Not Available]. PMID- 21012667 TI - [Not Available]. PMID- 21012668 TI - [Not Available]. PMID- 21012669 TI - [Not Available]. PMID- 21012670 TI - [Not Available]. PMID- 21012671 TI - [Not Available]. PMID- 21012672 TI - [Not Available]. PMID- 21012673 TI - [Not Available]. PMID- 21012674 TI - [Not Available]. PMID- 21012675 TI - [Not Available]. PMID- 21012676 TI - [Not Available]. PMID- 21012677 TI - [Not Available]. PMID- 21012678 TI - [Not Available]. PMID- 21012679 TI - [Not Available]. PMID- 21012680 TI - [Not Available]. PMID- 21012681 TI - [Not Available]. PMID- 21012683 TI - [Not Available]. PMID- 21012682 TI - [Not Available]. PMID- 21012684 TI - [Not Available]. PMID- 21012685 TI - [Not Available]. PMID- 21012686 TI - [Not Available]. PMID- 21012687 TI - [Not Available]. PMID- 21012688 TI - [Not Available]. PMID- 21012689 TI - [Not Available]. PMID- 21012690 TI - [Not Available]. PMID- 21012691 TI - [Not Available]. PMID- 21012692 TI - [Not Available]. PMID- 21012693 TI - [Not Available]. PMID- 21012694 TI - [Not Available]. PMID- 21012695 TI - [Not Available]. PMID- 21012696 TI - [Not Available]. PMID- 21012697 TI - [Not Available]. PMID- 21012698 TI - [Not Available]. PMID- 21012699 TI - [Not Available]. PMID- 21012700 TI - [Not Available]. PMID- 21012701 TI - [Not Available]. PMID- 21012702 TI - [Not Available]. PMID- 21012703 TI - [Not Available]. PMID- 21012704 TI - [Not Available]. PMID- 21012705 TI - [Not Available]. PMID- 21012706 TI - [Not Available]. PMID- 21012707 TI - [Not Available]. PMID- 21012708 TI - [Not Available]. PMID- 21012709 TI - [Not Available]. PMID- 21012710 TI - An improved radiation integrator for biological use. PMID- 21012711 TI - On the penetration of insecticides through the insect cuticle. PMID- 21012712 TI - Facilitation in sea anemones; the action of drugs. PMID- 21012714 TI - The mechanism of locomotion in gastropod molluscs; kinetics. PMID- 21012713 TI - Facilitation in sea anemones; tests on extracts. PMID- 21012715 TI - The fermentation of carbohydrates in the rumen of the sheep. PMID- 21012716 TI - Blood pressure and pulse rate in the foetal sheep. PMID- 21012717 TI - The mechanism of absorption from the rumen as exemplified by the behaviour of acetic, propionic and butyric acids. PMID- 21012718 TI - What are we doing about a dental health program? PMID- 21012719 TI - Caries control by chemical prophylaxis. PMID- 21012721 TI - Tympanic plexus tinnitus versus reflex dental tinnitus. PMID- 21012720 TI - The use of penicillin and sulpha drugs in root canal therapy. PMID- 21012722 TI - [Streptococcus viridans in paradentosis]. PMID- 21012723 TI - [The treatment of ulcerous stomatitis with phytoncide]. PMID- 21012724 TI - [The treatment of pulpitis and periodontitis with sodium chlor-phenol, after Lukomsky, in the polyclinic]. PMID- 21012725 TI - [Concerning the therapy of pulpitis]. PMID- 21012726 TI - [A method of local anesthetization in the treatment of acute periodontitis]. PMID- 21012727 TI - [Our methods of restoration of subtotal defects of the lips and mouth]. PMID- 21012728 TI - [On contracture of the jaws]. PMID- 21012729 TI - [Prophylaxis and treatment of contractures of the lower jaw]. PMID- 21012730 TI - [Bone plastics with local tissues]. PMID- 21012731 TI - [An apparatus for the treatment of contracture of the jaws following gunshot wounds]. PMID- 21012733 TI - A myelin staining method for old material. PMID- 21012732 TI - [On the teaching of the history of stomatology in stomatological institutes of the USSR]. PMID- 21012734 TI - Histochemical tests for proteins and amino acids; the characterization of basic proteins. PMID- 21012735 TI - A rapid histological technic for staining latex in roots of Taraxacum kok-sag hyz. PMID- 21012736 TI - A gold chloride method for motor end plates. PMID- 21012737 TI - Demonstration of the ground substance of cartilage, bone, and teeth. PMID- 21012738 TI - Carbol crystal violet. PMID- 21012739 TI - The transmission of infectious hepatitis by blood transfusion. PMID- 21012740 TI - The prophylaxis of peptic ulcer. PMID- 21012741 TI - The pancreas; contributions of clinical interest made in 1944. PMID- 21012742 TI - Tuberculosis of the stomach with special reference to its incidence in children. PMID- 21012743 TI - The methyl group and some of its relations to liver and kidney damage. PMID- 21012744 TI - Action of vitamin D2 on experimental peptic ulcer produced by cincophen. PMID- 21012745 TI - A pepsin method; the role of dilution in the determination of peptic activity. PMID- 21012746 TI - The effect of alumina gel upon the absorption of vitamin A from the intestinal tract. PMID- 21012747 TI - White bile. PMID- 21012749 TI - Bread enrichment. PMID- 21012748 TI - Was there sick headache in 3000 B. C.? PMID- 21012750 TI - Dermoid cysts of the ovary: their clinical and pathologic significance. PMID- 21012751 TI - The obstetrician's responsibility for the hazards of the first few days of life with special reference to anoxia and prematurity. PMID- 21012752 TI - Studies of surgical morbidity; effect of prostigmine on the urinary tract in gynecologic surgery. PMID- 21012753 TI - Cyclic variations in the viscosity of cervical mucus and its correlation with amount of secretion and basal temperature. PMID- 21012754 TI - Tubal sterilization. PMID- 21012755 TI - Early controlled ambulation in the puerperium. PMID- 21012756 TI - The anesthetic management of patients with respiratory paralysis requiring laparotomy. PMID- 21012757 TI - Pregnancy in cases of pituitary dwarfism. PMID- 21012758 TI - Etiology and treatment of heartburn of pregnancy. PMID- 21012759 TI - The routine use of stilbestrol for engorgement and lactation in nonnursing mothers. PMID- 21012760 TI - Penicillin in obstetrics; a preliminary survey. PMID- 21012761 TI - Presacral sympathectomy for intractable functional uterine pain. PMID- 21012762 TI - Initial fetal atelectasis. PMID- 21012763 TI - Neoplasms in apparently normal ovaries. PMID- 21012764 TI - Theca-cell cystoma of ovary. PMID- 21012765 TI - Granulosa-cell tumor with pregnancy following removal. PMID- 21012766 TI - A nearly ovarian pregnancy. PMID- 21012767 TI - Hydradenoma and hydradenoid carcinoma of the vulva. PMID- 21012768 TI - Extensive varix of vulva and vagina in full term pregnancy; delivery by cesarean section. PMID- 21012769 TI - Toxemia of pregnancy with unusual postmortem findings. PMID- 21012770 TI - Pregnancy complicating multiple sclerosis. PMID- 21012771 TI - Dystocia due to pelvic kidney. PMID- 21012772 TI - Subcutaneous thoracoplasty on the partially delivered impacted fetus; a substitute for embryotomy. PMID- 21012773 TI - A needle shield for continuous spinal anesthesia during labor and delivery. PMID- 21012774 TI - The Department of Obstetrics and Gynecology of Stanford University School of Medicine. PMID- 21012775 TI - [Not Available]. PMID- 21012776 TI - [Not Available]. PMID- 21012777 TI - [Not Available]. PMID- 21012778 TI - The physicians in the revolutionary assemblies. PMID- 21012779 TI - The physicians and the medical service of the revolutionary armies. PMID- 21012780 TI - Medical opinions on the reign of terror. PMID- 21012781 TI - Protection between strains of heterologous agglutinogenic types of beta hemolytic streptococci of group A. PMID- 21012782 TI - The standardization of the cardiolipin-lecithincholesterol antigen in the precipitation test for syphilis. PMID- 21012783 TI - Studies with the somatic antigen of Shigella para-dysenteriae (Flexner). PMID- 21012784 TI - The use of papaverine hydrochloride in the prevention of anaphylactic shock in guinea pigs. PMID- 21012785 TI - Studies on the effects of x-ray on phagocytic indices of healthy rabbits. PMID- 21012786 TI - Leukoagglutination differentiation of normal leukocytic and leukemic cell-types. PMID- 21012787 TI - A method of producing in inbred albino rats a high percentage of immunity from tumors native in their strain. PMID- 21012788 TI - Precipitin-reactions of human seminal plasma. PMID- 21012789 TI - Decreased antigenicity of coupled hapten-protein antigen resulting from treatment with too much hapten. PMID- 21012790 TI - The clinical and roentgenographic manifestations of primary atypical pneumonia, etiology unknown. PMID- 21012791 TI - The treatment of subacute bacterial endocarditis with penicillin; second report. PMID- 21012792 TI - Amebiasis in military overseas returnees. PMID- 21012793 TI - Tsutsugamushi fever; agglutination reactions and clinical observations in 25 cases. PMID- 21012794 TI - Asiatic relapsing fever; report of 134 cases treated with mapharsen. PMID- 21012795 TI - Cystic disease of the lung. PMID- 21012796 TI - A brief review of arthritis and allied conditions in tropical diseases. PMID- 21012797 TI - Lipoid pneumonia in adults. PMID- 21012798 TI - The recognition and clinical significance of auricular heart sounds. PMID- 21012799 TI - Mediterranean target-oval cell syndrome in an adult Chinese male; report of a case. PMID- 21012800 TI - Primary endothelioma of the pleura; report of a case in a patient with chronic lymphatic leukemia. PMID- 21012801 TI - Friedlander's bacillus meningitis with report of case treated unsuccessfully with sulfadiazine. PMID- 21012802 TI - Aplastic anemia following exposure to products of the sulfite pulp industry; a report of one case. PMID- 21012803 TI - BRIGHTER blood for blue babies. PMID- 21012804 TI - [Not Available]. PMID- 21012805 TI - [Not Available]. PMID- 21012806 TI - [Not Available]. PMID- 21012807 TI - [Not Available]. PMID- 21012808 TI - [Not Available]. PMID- 21012809 TI - [Not Available]. PMID- 21012810 TI - [Not Available]. PMID- 21012811 TI - [Not Available]. PMID- 21012812 TI - [Not Available]. PMID- 21012813 TI - [Not Available]. PMID- 21012814 TI - [Not Available]. PMID- 21012815 TI - Compensatory mechanisms related to the kidney. PMID- 21012817 TI - A case of rupture of the aorta into the third part of the duodenum. PMID- 21012816 TI - Therapeutic abortion. PMID- 21012818 TI - Osteoid-osteoma associated with myositis ossificans. PMID- 21012819 TI - A report on a proposed plan for graduate study at the School of Medicine, University of Maryland. PMID- 21012820 TI - Activities of the Department of Pharmacology during the war years. PMID- 21012821 TI - [Not Available]. PMID- 21012822 TI - [Not Available]. PMID- 21012823 TI - [Not Available]. PMID- 21012824 TI - [Not Available]. PMID- 21012825 TI - The constitution of strychnine. PMID- 21012826 TI - [Not Available]. PMID- 21012828 TI - [Not Available]. PMID- 21012827 TI - [Not Available]. PMID- 21012829 TI - Para- and peri-urethral infections of the female urethra. PMID- 21012830 TI - Sterility. PMID- 21012831 TI - Clinical evaluation of serologic tests for syphilis in eight thousand cases. PMID- 21012832 TI - Classification of strabismus. PMID- 21012833 TI - Bismuth subsalicylate in oil the treatment of choice in Vincent's angina. PMID- 21012834 TI - Hemochromatosis; clinical, chemical and pathological study of a case. PMID- 21012835 TI - The surgical treatment of essential hypertension. PMID- 21012836 TI - Effect of folic acid on persons with macrocytic anemia in relapse. PMID- 21012837 TI - Severe postoperative hypoglycemia. PMID- 21012838 TI - Uncommon clinical manifestations of vivax malaria. PMID- 21012839 TI - Streptomycin resistance of gonococci and meningococci. PMID- 21012840 TI - Rheumatic fever on the Isthmus of Panama. PMID- 21012841 TI - Sudden death following intravenous injection of thiamine hydrochloride. PMID- 21012842 TI - AMERICAN Medical Association health program and prepayment sickness insurance plans. PMID- 21012843 TI - Radioactive phosphorus as a therapuetic agent; a review of the literature and analysis of the results of treatment of 155 patients with various blood dyscrasias, lymphomas, and other malignant neoplastic diseases. PMID- 21012844 TI - The treatment of ulcerative colitis with nisulfadine and nisulfazole. PMID- 21012845 TI - Observations on the treatment of tropical sprue with folic acid. PMID- 21012846 TI - A method for determining the relative anticonvulsive activity of barbiturates. PMID- 21012847 TI - An in vitro method for determining the resistance of beta hemolytic streptococci to sulfadiazine. PMID- 21012848 TI - Effect of metals on Giemsa stain solutions in fifty per cent glycerol and methanol mixture. PMID- 21012849 TI - The ulcer problem. PMID- 21012851 TI - Chronic unstable colon. PMID- 21012850 TI - A high fluid intake regime in the management of edema; a review with some comments after four years. PMID- 21012852 TI - The doctor and his medical society. PMID- 21012853 TI - The diagnosis and treatment of the common anorectal diseases. PMID- 21012854 TI - Errors commonly encountered in cardiac diagnosis in military personnel. PMID- 21012855 TI - [Not Available]. PMID- 21012856 TI - [Not Available]. PMID- 21012857 TI - [Not Available]. PMID- 21012858 TI - [Not Available]. PMID- 21012859 TI - [Not Available]. PMID- 21012860 TI - [Not Available]. PMID- 21012861 TI - [Not Available]. PMID- 21012862 TI - Hormones. PMID- 21012863 TI - Glandular products. PMID- 21012864 TI - The vitamins. PMID- 21012865 TI - Vitamins. PMID- 21012866 TI - Protruded intervertebral disc. PMID- 21012867 TI - Some studies in dental public health. PMID- 21012868 TI - Malignancies of the rectum in the colored race. PMID- 21012869 TI - The conservative management of some varieties of placenta previa. PMID- 21012870 TI - Funnel chest; report of case successfully treated by chondro-sternal resection. PMID- 21012871 TI - Urgent maxillofacial surgery. PMID- 21012873 TI - Cancer of the small intestine. PMID- 21012872 TI - A new method for nasal decongestion and sinus drainage; preliminary report. PMID- 21012874 TI - The pathogenesis of the toxemias of late pregnancy. PMID- 21012875 TI - Incarceration of a Meckel's diverticulum in a femoral hernia. PMID- 21012876 TI - The cardiac glycosides. PMID- 21012877 TI - An analysis of three thousand seven-hundred-one admissions to the United States Public Health Service Medical Center in Durham, North Carolina. PMID- 21012878 TI - [Not Available]. PMID- 21012879 TI - [Not Available]. PMID- 21012880 TI - [Not Available]. PMID- 21012881 TI - [Not Available]. PMID- 21012882 TI - [Not Available]. PMID- 21012883 TI - [Not Available]. PMID- 21012885 TI - Recurrent meningo-encephalitis due to the virus of lymphogranuloma venereum. PMID- 21012884 TI - Epidemic hepatitis. PMID- 21012886 TI - Observarions on anorexia. PMID- 21012887 TI - Total abdominal hysterectomy. PMID- 21012888 TI - Another case of arrhenoblastoma. PMID- 21012889 TI - An evaluation of extraperitoneal cesarean section. PMID- 21012890 TI - Effects of therapeutic doses of x-ray and radium on the human uterus and uterine carcinomas. PMID- 21012891 TI - Changes in adenocarcinomas of the uterus. PMID- 21012892 TI - Glycosuria in dogs poisoned with uranyl nitrate, mercury bichloride, and potassium dichromate. PMID- 21012893 TI - Pneumosinus dilatans. PMID- 21012894 TI - Multiple myeloma; report of two cases. PMID- 21012895 TI - Streptomycin aerosol in the treatment of chronic bronchiectasis; preliminary report. PMID- 21012896 TI - Thrombo-angiitis obliterans among women; report of two cases. PMID- 21012897 TI - The syndrome of physical or intrinsic allergy of the head; vasomotor rhinitis and the vasodilating pain syndrome, their relationship to myalgia and endolymphatic hydrops (Meniere's disease) and the reasons for including all four as the syndrome of physical allergy of the head. PMID- 21012898 TI - Hand injuries and infections. PMID- 21012899 TI - Mass bleeding for blood transfusion and serum. PMID- 21012900 TI - Experiences as a prisoner-of-war. PMID- 21012901 TI - A case clinically resembling tabes dorsalis. PMID- 21012903 TI - A case of abscess of the left iliac region. PMID- 21012902 TI - Meningitis due to Torula histolitica. PMID- 21012904 TI - Complete luxation of the innominate bone. PMID- 21012905 TI - A case of acute aleukaemic myeloblastic leukaemia. PMID- 21012906 TI - [Not Available]. PMID- 21012907 TI - [Not Available]. PMID- 21012908 TI - [Not Available]. PMID- 21012910 TI - [Not Available]. PMID- 21012909 TI - [Not Available]. PMID- 21012911 TI - [Not Available]. PMID- 21012912 TI - [Not Available]. PMID- 21012913 TI - [Not Available]. PMID- 21012914 TI - [Not Available]. PMID- 21012915 TI - [Not Available]. PMID- 21012917 TI - [Not Available]. PMID- 21012916 TI - [Not Available]. PMID- 21012918 TI - [Not Available]. PMID- 21012920 TI - [Not Available]. PMID- 21012921 TI - [Not Available]. PMID- 21012919 TI - [Not Available]. PMID- 21012922 TI - [Not Available]. PMID- 21012923 TI - [Not Available]. PMID- 21012924 TI - Care of the filariasis patient. PMID- 21012925 TI - Problems of Naval warfare under climatic extremes. PMID- 21012926 TI - Medicine's campaign in Burma. PMID- 21012927 TI - Hookworm disease; its eradication again an international problem. PMID- 21012928 TI - Benign peptic ulcer as a diagnostic problem. PMID- 21012929 TI - The management of Army personnel with peptic ulcer; an analysis of 200 cases. PMID- 21012931 TI - Recurrent infectious hepatitis. PMID- 21012930 TI - Incidence of x-ray evidence of upper gastro-intestinal pathology in German prisoners of war. PMID- 21012932 TI - The field medical officer and psychiatry. PMID- 21012933 TI - Reconditioning program for combat neurosis in forward combat zones. PMID- 21012935 TI - VETERANS' Administration Department of Medicine and Surgery. PMID- 21012934 TI - The role of the psychological laboratory in the precourt-martial screening of military personnel charged with violations of the articles of war at McCloskey General Hospital. PMID- 21012936 TI - Traumatic lesions of peripheral nerves: experience in south Pacific area. PMID- 21012937 TI - Fractures of the patella. PMID- 21012938 TI - Chemical sympathectomy in neurovascular lesions of the upper extremity. PMID- 21012939 TI - Diving at U.S. Naval Torpedo Station, Newport, R.I., with emphasis on cases of bends occurring during 1944. PMID- 21012940 TI - Penicillin lozenges in the treatment of Vincent's stomatitis. PMID- 21012941 TI - Modified acrylic inlay. PMID- 21012942 TI - Skin lesions of rheumatic fever. PMID- 21012943 TI - Problem of recurrence in rheumatic fever. PMID- 21012944 TI - STUDIES on the primary isolation of influenza viruses. PMID- 21012945 TI - SEGREGATION of new and old recruits; effect on an epidemic. PMID- 21012946 TI - Deafness due to noises of warfare. PMID- 21012947 TI - Auditory impairment caused by drugs. PMID- 21012948 TI - A surgical service at a shore station. PMID- 21012949 TI - Experiences with x-ray on a hospital ship. PMID- 21012950 TI - Potassium acetate therapy in paroxysmal auricular fibrillation. PMID- 21012951 TI - Dextrocardia in association with a short P-R interval with prolongation of the QRS complex. PMID- 21012952 TI - Penicillin in treatment of Madura foot; report of two cases. PMID- 21012953 TI - Dentinogenesis imperfecta. PMID- 21012954 TI - Acute atabrine intoxication. PMID- 21012955 TI - Surgical method of treating tropical ulcer. PMID- 21012956 TI - A simple microtome for use aboard ship. PMID- 21012957 TI - Combined stretcher and treatment bed for transportation of pelvic and spinal injuries. PMID- 21012958 TI - Fumeless hot acid bath. PMID- 21012959 TI - Tsutsugamushi disease; epidemiology and methods of survey and control. PMID- 21012960 TI - Histopathologic effect of anoxia on the central nervous system. PMID- 21012961 TI - Neurologic manifestations associated with malaria in ducks. PMID- 21012962 TI - Nystagmus; an appraisal and a classification. PMID- 21012963 TI - Onset of Guillain-Barre syndrome following exposure to mustard gas. PMID- 21012964 TI - Nerve regeneration on vitamin B-deficient diets. PMID- 21012965 TI - Genetic and conditioning factors in susceptibility to disease. PMID- 21012966 TI - Relation of life situations, emotions and nasal function. PMID- 21012967 TI - Incidence of infections of the upper respiratory tract in relation to emotional reactions and adjustment. PMID- 21012968 TI - Resection of the superior longitudinal sinus. PMID- 21012969 TI - The vasomotor component of labyrinthine vertigo. PMID- 21012970 TI - Reflex pupillodilator mechanism; an experimental analysis. PMID- 21012971 TI - Effects of inhibitors of choline esterase on the nerve action potential. PMID- 21012972 TI - The mechanism of the electrophonic effect. PMID- 21012973 TI - Rapid changes in cerebral oxygen tension induced by altering the oxygenation and circulation of the blood. PMID- 21012974 TI - Carbonic anhydrase in the nervous system. PMID- 21012975 TI - The effect of cellular hydration on experimental electroshock convulsions. PMID- 21012976 TI - Recovery of motor function after two-stage extirpation of area 4 in monkeys. PMID- 21012977 TI - [Not Available]. PMID- 21012978 TI - [Not Available]. PMID- 21012979 TI - [Not Available]. PMID- 21012980 TI - [Not Available]. PMID- 21012981 TI - Anxiety and plane flight. PMID- 21012982 TI - Toward the problem of the musical process. PMID- 21012983 TI - A clinical contribution to the analysis of the nightmare syndrome. PMID- 21012984 TI - The anatomy of a psychosis. PMID- 21012985 TI - Dream analysis of a constitutional psychopath: toward the problem of differential dream analysis. PMID- 21012986 TI - Ocular cysticercus cellulosae; report of a case of parasite in vitreous. PMID- 21012987 TI - Tangential displacement of the iris in chronic glaucoma. PMID- 21012988 TI - Temporary cataracts in diabetes. PMID- 21012989 TI - Solar eclipse-burn of macula. PMID- 21012990 TI - A case of eclipse blindness. PMID- 21012991 TI - A case of siderosis bulbi. PMID- 21012992 TI - The effect of operative alterations in the height of the external rectus insertion. PMID- 21012993 TI - Meningioma of the tuberculum sellae with bi-temporal hemianopia. PMID- 21012994 TI - Dacrocystorhinostomy. PMID- 21012995 TI - Localisation of intra-ocular foreign bodies. PMID- 21012996 TI - [Not Available]. PMID- 21012997 TI - On adaptation. PMID- 21012998 TI - [Not Available]. PMID- 21013000 TI - [Not Available]. PMID- 21013001 TI - [Not Available]. PMID- 21012999 TI - [Not Available]. PMID- 21013002 TI - [Not Available]. PMID- 21013003 TI - [Not Available]. PMID- 21013004 TI - The importance of use of absorption lenses in tropical zones. PMID- 21013005 TI - The functional effect of loading of the tympanic membrane. PMID- 21013006 TI - Experimental histological studies on the labyrinth; comparison between the results of fixation with Wittmaack's fluid and with susa. PMID- 21013007 TI - [Not Available]. PMID- 21013009 TI - Nasal diphtheria as the cause of septum perforation. PMID- 21013008 TI - Investigations in the effect of chemotherapy on acute middle ear affections. PMID- 21013010 TI - A case of osteomyelitis in the flat bones of the skull, treated with penicillin. PMID- 21013011 TI - [Not Available]. PMID- 21013012 TI - Paravertebral anesthesia of plexus cervicalis. PMID- 21013013 TI - A case of mycosis in the frontal sinus. PMID- 21013014 TI - Tonsillectomy; general or local anesthesia? an account of 500 patients operated upon under ether anesthesia. PMID- 21013015 TI - Acute suppurative otitis media in infants. PMID- 21013016 TI - Hereditary character of the cellular system in the mastoid process. PMID- 21013017 TI - Frequent colds; swelling of the neck. PMID- 21013018 TI - Vomiting. PMID- 21013019 TI - Fever; vomiting; abdominal pain. PMID- 21013020 TI - Bowel disturbance. PMID- 21013021 TI - Irritability; excessive perspiration. PMID- 21013022 TI - BEEF, iron and wine. PMID- 21013023 TI - EPHEDRINE sulfate and phenobarbital capsules. PMID- 21013024 TI - FERRIC cacodylate. PMID- 21013025 TI - FERRCUS sulfate syrup. PMID- 21013026 TI - HYDRASTIS. PMID- 21013027 TI - LITHIUM bromide. PMID- 21013028 TI - MAGNESIUM phosphate, tribasic. PMID- 21013029 TI - MERBROMIN solution. PMID- 21013030 TI - NUX vomica. PMID- 21013031 TI - NUX vomica tincture. PMID- 21013032 TI - OPIUM extract. PMID- 21013033 TI - RESORCINOL monoacetate. PMID- 21013034 TI - STERCULIA gum. PMID- 21013035 TI - STIBOPHEN. PMID- 21013036 TI - The effect of electrical stimulation upon the course of atrophy and recovery of the gastrocnemius of the rat. PMID- 21013037 TI - The influence of adrenalin on plasma prothrombin. PMID- 21013038 TI - The cardiac output in man; a study of some of the errors in the method of right heart catheterization. PMID- 21013039 TI - The beneficial effects of yeast on the body and gonadal weight of immature rats fed alpha-estradiol. PMID- 21013040 TI - The relationship of cardiac glycogen deposition to blood ketone levels in experimental ketosis. PMID- 21013041 TI - The reflex activation of the vasodilator fibers of the dorsal roots and their role in vasodilator tone. PMID- 21013042 TI - The production of acetylcholine in antidromic vasodilatation. PMID- 21013043 TI - Blood histamine levels in experimental burns. PMID- 21013044 TI - The renal reabsorption of amino acids in dogs; valine, leucine and isoleucine. PMID- 21013045 TI - Supplementary effects of arsenic and manganese on copper in the synthesis of hemoglobin. PMID- 21013046 TI - The development and contour of cardiac injury potential. PMID- 21013047 TI - Pulse reaction to performing step-up exercise on benches of different heights. PMID- 21013048 TI - The action of cardiac ejection on venous return. PMID- 21013049 TI - Further observations concerning effect of adrenalectomy on alloxan diabetes; paired feeding experiments. PMID- 21013050 TI - Release of phosphate by the brain upon stimulation. PMID- 21013051 TI - The effect of dose and nutritive state on the renotrophic and androgenic activities of various steroids. PMID- 21013052 TI - The metabolism of acetate by the completely isolated mammalian heart investigated with carboxyl-labeled acetate. PMID- 21013053 TI - Provisual red and visual red. PMID- 21013054 TI - Experiments to ascertain the effect of manganese on the synthesis of ascorbic acid in the guinea pig. PMID- 21013055 TI - Changes in protein content and in some physicochemical properties of the protein during muscular atrophies of various types. PMID- 21013056 TI - The effect of daily electrical stimulation of normal and denervated muscles upon their protein content and upon some of the physicochemical properties of the protein. PMID- 21013057 TI - Spontaneous recovery of muscle following partial denervation. PMID- 21013058 TI - Effect of some isocyclic, aromatic and heterocyclic compounds on muscle sensitivity to acetylcholine and potassium. PMID- 21013059 TI - The configuration of epicardial and endocardial extrasystoles in the chest leads. PMID- 21013060 TI - Some factors influencing the biochemical appraisal of group nutritional status. PMID- 21013061 TI - [Not Available]. PMID- 21013062 TI - [Not Available]. PMID- 21013063 TI - [Not Available]. PMID- 21013064 TI - Quantitative aspects of antigen-antibody reactions. PMID- 21013065 TI - Quantitative aspects of antigen-antibody reactions; some comparisons between the theory and the experimental results. PMID- 21013066 TI - Studies in the dynamics of disinfection; the temperature coefficient of the reaction between phenol and Bact. coli, derived from data obtained by an improved technique. PMID- 21013067 TI - Studies in the dynamics of disinfection; calculation of a new and constant temperature coefficient for the reaction between phenol and Bact. coli. PMID- 21013068 TI - Warm-stage observations on the development of pseudomycelia in cultures of avian tubercle bacilli grown in dilute embryo extract. PMID- 21013069 TI - The differentiation of Streptococcus cremoris and Streptococcus lactis by means of bacteriophage action. PMID- 21013070 TI - A thermolabile substance of Shigella dysenteriae Shiga. PMID- 21013071 TI - Fluorine alopecia. PMID- 21013072 TI - Enteric fevers in Egypt. PMID- 21013073 TI - Three rapid tests for the estimation of tropical fitness of fabrics. PMID- 21013074 TI - A routine method of bacteriological analysis and grading of ice-creams; with records of eleven years' application. PMID- 21013075 TI - A.L.-63, the original British Army louse powder. PMID- 21013076 TI - The history of an experiment in the treatment of gynaecological cases in an Emergency Medical Services hospital during the years 1942-43. PMID- 21013077 TI - Housing survey; a new U.S. method. PMID- 21013078 TI - Notes on conditions which may lead to a provisional diagnosis of cancer but which prove to be non-malignant histologically. PMID- 21013079 TI - Human carriers in the spread of poliomyelitis. PMID- 21013080 TI - Three outbreaks of staphylococcal food poisoning due to ice-cream. PMID- 21013081 TI - Anterior nasal diphtheria. PMID- 21013082 TI - The rapid detection of gelatin-liquefying organisms. PMID- 21013083 TI - Foods, drugs and cosmetics salvaged from 1945 flood. PMID- 21013084 TI - Women's role in the control of venereal disease. PMID- 21013085 TI - Environmental conditions in plants molding lead plastic bullets. PMID- 21013086 TI - [Not Available]. PMID- 21013088 TI - [Not Available]. PMID- 21013087 TI - [Not Available]. PMID- 21013089 TI - [Not Available]. PMID- 21013090 TI - [Not Available]. PMID- 21013091 TI - [Not Available]. PMID- 21013092 TI - [Not Available]. PMID- 21013093 TI - [Not Available]. PMID- 21013094 TI - [Not Available]. PMID- 21013095 TI - [Not Available]. PMID- 21013096 TI - [Not Available]. PMID- 21013098 TI - [Not Available]. PMID- 21013097 TI - [Not Available]. PMID- 21013099 TI - [Not Available]. PMID- 21013100 TI - [Not Available]. PMID- 21013101 TI - [Not Available]. PMID- 21013102 TI - [Not Available]. PMID- 21013104 TI - [Not Available]. PMID- 21013103 TI - [Not Available]. PMID- 21013105 TI - [Not Available]. PMID- 21013106 TI - [Not Available]. PMID- 21013107 TI - [Not Available]. PMID- 21013108 TI - The Roentgen anatomy of the skull in the newborn infant. PMID- 21013109 TI - Mid-line anomalies of the brain; their diagnosis by pneumoencephalography. PMID- 21013110 TI - Lesions of the aqueduct of Sylvius. PMID- 21013111 TI - Observations on the presence of subdural gas after pneumoencephalography. PMID- 21013113 TI - The treatment of hemangioma. PMID- 21013112 TI - The treatment of late post-irradiation ulcers with radon ointment. PMID- 21013114 TI - The value of stereoscopy in mass radiography of the chest. PMID- 21013115 TI - A comparison of two levels of Roentgen and neutron irradiation of normal and lymphomatous mice, using radiophosphorus as an indicator of cellular activity. PMID- 21013116 TI - Some observations on x-ray treatment cones. PMID- 21013117 TI - The latent period which elapses between the onset of a lesion and the appearance of radiographic signs. PMID- 21013118 TI - [Not Available]. PMID- 21013119 TI - [Not Available]. PMID- 21013120 TI - [Not Available]. PMID- 21013121 TI - [Not Available]. PMID- 21013122 TI - [Not Available]. PMID- 21013123 TI - [Not Available]. PMID- 21013124 TI - [Not Available]. PMID- 21013125 TI - [Not Available]. PMID- 21013126 TI - [Not Available]. PMID- 21013127 TI - [Not Available]. PMID- 21013128 TI - [Not Available]. PMID- 21013129 TI - [Not Available]. PMID- 21013130 TI - [Not Available]. PMID- 21013131 TI - [Not Available]. PMID- 21013132 TI - [Not Available]. PMID- 21013133 TI - [Not Available]. PMID- 21013134 TI - [Not Available]. PMID- 21013136 TI - [Not Available]. PMID- 21013135 TI - [Not Available]. PMID- 21013137 TI - [Not Available]. PMID- 21013138 TI - [Not Available]. PMID- 21013139 TI - The use of methedrine as a vasooonstrictor with spinal anesthesia. PMID- 21013140 TI - Convulsions produced by fetal anoxia; experimental study. PMID- 21013141 TI - Curare; misconceptions regarding the discovery and development of the present form of the drug. PMID- 21013142 TI - Curare and nitrous oxide anesthesia for lengthy operations. PMID- 21013143 TI - The effect of various surgical positions on vital capacity. PMID- 21013144 TI - Further experiences with endotracheal ether-air anesthesia for intrathoracic surgery. PMID- 21013145 TI - Clinical studies on morphine; the effect of morphine upon the circulation of man and upon the circulatory and respiratory responses to tilting. PMID- 21013146 TI - The efficiency of oenethyl (2, methyl amino heptane) as a vasopressor substance for spinal anesthesia. PMID- 21013147 TI - Anesthetic complications and their management. PMID- 21013148 TI - An oxygen analyzer for hospital use. PMID- 21013149 TI - A simplified dripper for open drop anesthesia. PMID- 21013150 TI - [Not Available]. PMID- 21013151 TI - [Not Available]. PMID- 21013152 TI - [Not Available]. PMID- 21013153 TI - [Not Available]. PMID- 21013154 TI - [Not Available]. PMID- 21013155 TI - [Not Available]. PMID- 21013156 TI - [Not Available]. PMID- 21013157 TI - [Not Available]. PMID- 21013158 TI - [Not Available]. PMID- 21013159 TI - [Not Available]. PMID- 21013160 TI - [Not Available]. PMID- 21013162 TI - [Not Available]. PMID- 21013161 TI - [Not Available]. PMID- 21013163 TI - [Not Available]. PMID- 21013164 TI - Pancreatitis; an anatomic study of the pancreatic and extrahepatic biliary systems. PMID- 21013165 TI - Sludged blood in traumatic shock; microscopic observations of the precipitation and agglutination of blood flowing through vessels in crushed tissues. PMID- 21013166 TI - A new treatment for postoperative pulmonary collapse. PMID- 21013167 TI - Electrolyte changes and chemotherapy in experimental burn and traumatic shock and hemorrhage. PMID- 21013168 TI - Gelatin sponge, a new hemostatic substance; studies on absorbability. PMID- 21013169 TI - Breast cancer and Paget's disease of the breast. PMID- 21013171 TI - Congenital dislocation of the hip. PMID- 21013170 TI - Skeletal fixation of mandibular fractures; report of five cases, with nine fractures. PMID- 21013173 TI - Chronic arthritis. PMID- 21013172 TI - Tuberculosis of bones and joints. PMID- 21013174 TI - Infantile paralysis. PMID- 21013175 TI - Poliomyelitis. PMID- 21013176 TI - Poliomyelitis; convalescent treatment and related subjects. PMID- 21013178 TI - [Not Available]. PMID- 21013177 TI - Neuromuscular disorders exclusive of poliomyelitis. PMID- 21013179 TI - [Not Available]. PMID- 21013180 TI - [Not Available]. PMID- 21013181 TI - [Not Available]. PMID- 21013182 TI - [Not Available]. PMID- 21013183 TI - [Not Available]. PMID- 21013184 TI - [Not Available]. PMID- 21013185 TI - [Not Available]. PMID- 21013186 TI - [Not Available]. PMID- 21013187 TI - [Not Available]. PMID- 21013188 TI - [Not Available]. PMID- 21013189 TI - [Not Available]. PMID- 21013190 TI - [Not Available]. PMID- 21013191 TI - [Not Available]. PMID- 21013192 TI - [Not Available]. PMID- 21013193 TI - [Not Available]. PMID- 21013194 TI - Intravenous procaine analgesia. PMID- 21013195 TI - Military aspects of early analgesia and anesthesia. PMID- 21013196 TI - Ether convulsions; discussion and presentation of a case. PMID- 21013197 TI - [Not Available]. PMID- 21013198 TI - [Not Available]. PMID- 21013199 TI - [Not Available]. PMID- 21013200 TI - [Not Available]. PMID- 21013201 TI - [Not Available]. PMID- 21013202 TI - [Not Available]. PMID- 21013204 TI - [Not Available]. PMID- 21013203 TI - [Not Available]. PMID- 21013205 TI - [Not Available]. PMID- 21013206 TI - [Not Available]. PMID- 21013207 TI - [Not Available]. PMID- 21013208 TI - [Not Available]. PMID- 21013209 TI - [Not Available]. PMID- 21013210 TI - [Not Available]. PMID- 21013211 TI - [Not Available]. PMID- 21013212 TI - [Not Available]. PMID- 21013213 TI - [Not Available]. PMID- 21013214 TI - [Not Available]. PMID- 21013215 TI - [Not Available]. PMID- 21013216 TI - Menstrual dysfunctions; amenorrhea, oligomennorrhea, and hypomenorrhea. PMID- 21013217 TI - The Rh factor; a review and critical analysis. PMID- 21013218 TI - Case report of the use of a dual onlay graft and penicillin in an infected bone defect. PMID- 21013219 TI - Gastric adenoids; a pathologic study. PMID- 21013220 TI - Psychosomatic concepts in physical medicine. PMID- 21013221 TI - Physical therapy and reconditioning therapy at Fitzsimons General Hospital, Denver. PMID- 21013222 TI - Pulley exercises to increase joint movement. PMID- 21013223 TI - Ultraviolet blood irradiation therapy of apparently intractable bronchial asthma. PMID- 21013224 TI - Preventive measures in plaster cast application. PMID- 21013225 TI - Muscle and joint examination charts. PMID- 21013227 TI - Neurosis. PMID- 21013226 TI - Physiotherapy and head injury. PMID- 21013228 TI - Pointers for the intelligent practice of occupational therapy in a tuberculosis institution. PMID- 21013229 TI - The value of the prosthesis training program at McCloskey General Hospital as an aid to amputees in developing confidence and ability prior to their return to civilian life. PMID- 21013230 TI - The importance of the family in rehabilitation. PMID- 21013231 TI - Getting stairborne for a start. PMID- 21013232 TI - The use of song parodies as recreational therapy for mental patients. PMID- 21013233 TI - SIMPLE devices enable veterans to drive motor vehicles safely. PMID- 21013234 TI - A history of the American Physiotherapy Association. PMID- 21013235 TI - An improved hand table. PMID- 21013236 TI - Reconditioning program in an overseas general hospital. PMID- 21013238 TI - MAPHARSEN therapy of early syphilis. PMID- 21013239 TI - SIBLIN in functional constipation. PMID- 21013237 TI - EDUCATIONAL plans for returning physical therapy veterans. PMID- 21013240 TI - [Not Available]. PMID- 21013241 TI - [Not Available]. PMID- 21013242 TI - [Not Available]. PMID- 21013243 TI - Studies on synthetic antimalarial drugs; biological methods. PMID- 21013244 TI - Studies on synthetic antimalarial drugs; general chemical considerations. PMID- 21013245 TI - Studies on synthetic antimalarial drugs; a preliminary investigation of the therapeutic action of 3349 on acute attacks of benign tertian malaria. PMID- 21013246 TI - Studies on synthetic antimalarial drugs; a preliminary investigation of the therapeutic action of 3349 on acute attacks of malignant tertian malaria. PMID- 21013247 TI - Studies on synthetic antimalarial drugs; further investigation of the therapeutic action of 3349 on benign tertian and on malignant tertian malaria infections. PMID- 21013248 TI - Studies on synthetic antimalarial drugs; a comparison of the therapeutic actions of 3349 and of mepacrine hydrochloride on acute attacks of benign tertian malaria. PMID- 21013249 TI - Studies on synthetic antimalarial drugs; turbidimetric determination of 2-p chlorophenylguanidino-4-Beta-diethylaminoethyl-amino-6-methylpyrimidine (3349). PMID- 21013250 TI - Studies on synthetic antimalarial drugs; colorimetric determination of 2-p chlorophenylguanidino-4-diethylaminoethyl-amino-6-methylpyrimidine (3349). PMID- 21013251 TI - Studies on synthetic antimalarial drugs; the excretion of 2-p chlorophenylguanidino-4-Beta-diethylaminoethylamino-6-methylpyrimidine (3349) in human urine. PMID- 21013252 TI - Studies on synthetic antimalarial drugs; some biguanide derivatives as new types of antimalarial substances with both therapeutic and causal prophylactic activity. PMID- 21013253 TI - Studies on synthetic antimalarial drugs; an investigation of the therapeutic action of 4430 on benign and malignant teritan malaria. PMID- 21013254 TI - Studies on synthetic antimalarial drugs; determination of N1-p-chlorophenyl-N5 methyl-N5-isopropylbiguanide (4430) and N1-p-chlorophenyl-N5-isopropylbiguanide (paludrine); a preliminary report. PMID- 21013255 TI - Studies on synthetic antimalarial drugs; results of a preliminary investigation of the therapeutic action of 4888 (paludrine) on acute attacks of benign tertian malaria. PMID- 21013256 TI - Studies on synthetic antimalarial drugs; results of a preliminary investigation of the therapeutic action of 4888 (paludrine) on acute attacks of malignant tertian malaria. PMID- 21013257 TI - Speed of reaction hypothesis; further numerical implications regarding tuberculosis. PMID- 21013258 TI - Electrocardiograms in chronic pulmonary disease; a theoretical interpretation. PMID- 21013259 TI - Bronchiolar spasm as a cause of reexpansion of a lung following intrapleural pneumonolysis. PMID- 21013260 TI - Respiratory malformations; types, causes and significance; a preliminary report. PMID- 21013261 TI - The effect of purified fractions of tuberculin on tuberculin sensitive tissue; quantitative studies on tissue cultures. PMID- 21013262 TI - The tuberculostatic action of the sodium salts of certain synthetic alicyolic acids. PMID- 21013263 TI - [Not Available]. PMID- 21013264 TI - [Not Available]. PMID- 21013265 TI - [Not Available]. PMID- 21013266 TI - Pneumoperitoneum in the treatment of pulmonary tuberculosis. PMID- 21013267 TI - A current theory on aspiration of lung cavities (Monaldi). PMID- 21013268 TI - Studies of tuberculosis considering relationship and family history; summary of analyses from Williamson County Tuberculosis Study. PMID- 21013269 TI - Frequency of tuberculous lesions at autopsy; some epidemiological inferences. PMID- 21013270 TI - A transition in viewpoint of certain intimate mechanisms of tuberculosis. PMID- 21013271 TI - Angioma of the kidney. PMID- 21013272 TI - A case of pyelitis and cystitis cystica. PMID- 21013273 TI - Malignant hypertension; neurosurgery of the kidney. PMID- 21013274 TI - Prevention and treatment of delayed wound healing and ulcerative cystitis following surgery for tuberculosis of the genitourinary tract. PMID- 21013275 TI - Xanthine urinary calculi; report of two cases. PMID- 21013276 TI - Seminal vesiculitis (congestive) simulating acute abdominal disease. PMID- 21013277 TI - War wounds of the urogenital tract. PMID- 21013278 TI - Primary malignant tumors of the retrovesical region with special reference to malignant tumors of the seminal vesicles; report of a case of retrovesical sarcoma. PMID- 21013279 TI - An automatic stabilizer of water pressure. PMID- 21013280 TI - A new cystoscope. PMID- 21013281 TI - [Not Available]. PMID- 21013282 TI - [Not Available]. PMID- 21013283 TI - [Not Available]. PMID- 21013284 TI - Suprapubic prostatectomy. PMID- 21013285 TI - Carcinoma of the urachus; report of two cases. PMID- 21013286 TI - The supra-pubic repair of vesico-vaginal fistula. PMID- 21013287 TI - Evolution in the diagnosis and prognosis of renal tuberculosis. PMID- 21013288 TI - Performation of the digestive organs secondary to disease of the kidney; report of an instance of a gastric and a colonic fistula which developed several months following the removal of a tubeculous kidney. PMID- 21013290 TI - Traumatism of the testicle; report of a case of traumatic rupture of a solitary testicle. PMID- 21013289 TI - Horseshoe kidney with a calculus in one side and hydronephrosis on the other side. PMID- 21013291 TI - Vesical diverticula; a contribution to their diagnosis and treatment. PMID- 21013292 TI - Retroperitoneal pelvic lymphangitis. PMID- 21013293 TI - An operation for varicocele. PMID- 21013294 TI - Elective dilatation of the calyces. PMID- 21013295 TI - Is ureteral stricture an etiological factor in the genesis of renal cancer? PMID- 21013296 TI - Experimental post-traumatic hypertension. PMID- 21013297 TI - Occipital lichenification in women. PMID- 21013298 TI - Eczema of the hands--is it a diagnosis of ignorance? PMID- 21013299 TI - Experimental gonococcic urethritis in human volunteers. PMID- 21013300 TI - Cardiolipin antigens in the serodiagnosis of syphilis; a microflocculation slide test. PMID- 21013301 TI - The relative prophylactic effectiveness against syphilis of ointments containing calomel in different particle size. PMID- 21013302 TI - Congenital syphilis; report of possible third generation syphilis with fatal spontaneous cerebral hemorrhage. PMID- 21013303 TI - Syphilitic vascular or cardiovascular disease occurring in early adult life following acquired syphilitic infection. PMID- 21013304 TI - Studies on liver function; the value of laboratory tests in the prevention of arsenical toxicity with report of two unusual cases of encephalopathy. PMID- 21013305 TI - The relative efficacy of three treatment routines for gonorrheal urethritis in the adult male. PMID- 21013306 TI - The mucoid phases of the genus Brucella. PMID- 21013307 TI - Studies on brucellosis of swine; exposure and reexposure experiments with Brucella suis. PMID- 21013308 TI - Brucellosis of swine; the unit segregation system of eradication. PMID- 21013309 TI - Effect of temperature, phenol, and crystal violet on vesicular stomatitis virus. PMID- 21013310 TI - Reservoirs of infection of Streptococcus agalactiae. PMID- 21013311 TI - The carbon dioxide content of the blood of dairy cattle. PMID- 21013312 TI - The etiology of calf diphtheria. PMID- 21013313 TI - Chemotherapy of Trichomonas foetus (Protozoa) in vitro. PMID- 21013314 TI - The influence of protein diets on selenium poisoning. PMID- 21013315 TI - The influence of protein diets on selenium poisoning; the chemical changes in the tissues following selenium administration. PMID- 21013316 TI - Salmonella from Galapagos turtles, a gila monster, and an iguana. PMID- 21013317 TI - A preliminary report on the treatment of clinical and subclinical streptococcal and staphylococcal infections of the bovine udder with penicillin. PMID- 21013318 TI - Phenothiazine as an anthelmintic. PMID- 21013319 TI - Artificial insemination of cows. PMID- 21013320 TI - The vaccination of poultry against infectious laryngotracheitis. PMID- 21013321 TI - CONTROL of trichostrongylosis in sheep; the use of phenothiazine and tetrachlorethylene as substitutes for nicotin. PMID- 21013322 TI - Lesions in sheep attributed to Strongyloides larvae. PMID- 21013323 TI - On the chemotherapy of caecal coccidiosis (Eimeria tenella) of chickens; further studies on the use of drugs in established infections. PMID- 21013324 TI - Studies in infectious mastitis; penicillin as a therapeutic agent. PMID- 21013325 TI - Observations on neoplasmata of the tegumentary system of the domesticated animals. PMID- 21013326 TI - Animal parasitism. PMID- 21013327 TI - Canaries and their common ailments. PMID- 21013328 TI - The occurrence of bovine contagious pleuropneumonia in Assam. PMID- 21013329 TI - Veterinary propaganda. PMID- 21013330 TI - A case of pyaemia due to traumatic reticulitis. PMID- 21013331 TI - Glanders in the ass. PMID- 21013332 TI - Caprine contagious pleuro-pneumonia. PMID- 21013333 TI - 693 (dagenan) in rinderpest. PMID- 21013334 TI - A case of traumatic pericarditis in ox. PMID- 21013336 TI - Some interesting observations in the study of protozoal diseases. PMID- 21013335 TI - Cibazol in canine distemper. PMID- 21013337 TI - Use of sulfanilamide in cases of retained placenta. PMID- 21013338 TI - Crotalaria spectabilis poisoning in Louisiana livestock. PMID- 21013339 TI - Ketosis in the Hawaiian Islands. PMID- 21013340 TI - The world livestock situation and the war. PMID- 21013341 TI - Effects of stilbestrol in retained placenta. PMID- 21013342 TI - Tetanus fails to respond to penicillin. PMID- 21013343 TI - Ablation of the scent glands of skunks. PMID- 21013344 TI - Sulfathalidine in the treatment of enteric infections of small animals. PMID- 21013345 TI - Treatment of interdigital phlegmon (foul claw) with sulfasuxidine and sulfathalidine. PMID- 21013346 TI - An outbreak of pasteurellosis in wild ducks. PMID- 21013347 TI - Treatment of Pasteurella multocida (fowl cholera) infection in wild ducks with autogenous bacterin and penicillin. PMID- 21013348 TI - COBALT deficiency. PMID- 21013349 TI - DDT treatment of mange (scabies) in rabbits. PMID- 21013350 TI - Vesicular stomatitis in cattle and horses in Colorado. PMID- 21013351 TI - Anesthesia and surgery in the monkey and the ant-eater. PMID- 21013352 TI - Directions for making animal cages. PMID- 21013353 TI - HOSPITAL cage construction. PMID- 21013354 TI - [Not Available]. PMID- 21013355 TI - [Not Available]. PMID- 21013356 TI - [Not Available]. PMID- 21013357 TI - [Not Available]. PMID- 21013358 TI - [Not Available]. PMID- 21013359 TI - [Not Available]. PMID- 21013360 TI - [Not Available]. PMID- 21013361 TI - [Not Available]. PMID- 21013362 TI - [Not Available]. PMID- 21013363 TI - [Not Available]. PMID- 21013364 TI - [Not Available]. PMID- 21013365 TI - [Not Available]. PMID- 21013366 TI - [Not Available]. PMID- 21013367 TI - [Not Available]. PMID- 21013368 TI - [Not Available]. PMID- 21013369 TI - The adrenals of the horse. PMID- 21013370 TI - Some observations on the incidence of bovine helminths in Plateau Province, Northern Nigeria. PMID- 21013371 TI - Capon production by the use of synthetic oestrogen (stilboestrol). PMID- 21013372 TI - Sex hormones in veterinary practice. PMID- 21013373 TI - DISEASES of sheep. PMID- 21013374 TI - A veterinarian's experiences on the roof of the world. PMID- 21013375 TI - Double cervix in a cow. PMID- 21013376 TI - Carcinoma of the maxillary sinus in a horse. PMID- 21013377 TI - Traumatic splenitis in a dairy cow. PMID- 21013378 TI - Observations on the treatment of avian coccidiosis (cecal). PMID- 21013379 TI - Modified technic for red cell determination in goats. PMID- 21013380 TI - Bovine surgery. PMID- 21013381 TI - The treatment of acute infectious bovine mastitis with penicillin. PMID- 21013382 TI - Abortion in swine. PMID- 21013383 TI - Posterior paralysis in a dog. PMID- 21013384 TI - Preparation of skeletons. PMID- 21013385 TI - Prolapse of vagina due to proliferative growth. PMID- 21013386 TI - Histochemical reactions in the placenta of the cat. PMID- 21013387 TI - A histochemical and quantitative study of phosphatase in the placenta and fetal membranes of the guinea pig. PMID- 21013388 TI - The histology of the tadpole tail during metamorphosis, with special reference to the nervous system. PMID- 21013390 TI - ANATOMICAL nomenclature. PMID- 21013389 TI - Experiments upon the midbrain of Amblystoma embryos. PMID- 21013391 TI - Stages in the normal development of Rana pipiens larvae. PMID- 21013392 TI - Differences in rats of various strains shown by their rate of response to carcinogenic agents. PMID- 21013393 TI - Monozygotic twins in the dog. PMID- 21013394 TI - Deep lymphatics of the spleen. PMID- 21013395 TI - Experimental studies on the movements of the mammalian tongue; the protrusion mechanism of the tongue (dog). PMID- 21013396 TI - Neurosecretion; cytoplasmic inclusions in peripheral autonomic ganglion cells of the monkey. PMID- 21013397 TI - On the relative frequency of variant types of the vena cava posterior in the cat. PMID- 21013398 TI - Pre-implantation stages in the golden hemster (Cricetus auratus). PMID- 21013399 TI - [Not Available]. PMID- 21013400 TI - [Not Available]. PMID- 21013401 TI - [Not Available]. PMID- 21013402 TI - [Not Available]. PMID- 21013403 TI - [Not Available]. PMID- 21013404 TI - [Not Available]. PMID- 21013405 TI - [Not Available]. PMID- 21013406 TI - [Not Available]. PMID- 21013407 TI - [Not Available]. PMID- 21013408 TI - [Not Available]. PMID- 21013409 TI - [Not Available]. PMID- 21013410 TI - [Not Available]. PMID- 21013411 TI - [Not Available]. PMID- 21013412 TI - Sulfamerazine therapy in experimental cecal coccidiosis of chickens. PMID- 21013413 TI - Effect of sulfaguanidine on the course of infection in chickens with Eimeria tenella. PMID- 21013414 TI - Variations in response to filariform larvae of Ancylostoma caninum in the skin of man. PMID- 21013415 TI - The cultivation of Trichomonas augusta (Protozoa) from frogs. PMID- 21013416 TI - Physiological observations upon a larval Eustrongylides; influence of respiratory poisons upon the aerobic gaseous metabolism. PMID- 21013417 TI - Notes on the gapeworms (Nematoda; Syngamidae) of galliform and passeriform birds in New York State. PMID- 21013418 TI - Two new species of Acariscus: A. pluvius and A. anous (Acarinida: Trombiculidae). PMID- 21013419 TI - Comparison between in vitro and in vivo glycogen utilization in the fowl nematode Ascaridia galli. PMID- 21013420 TI - Dermadena lactophrysi n. gen., n. sp. (Trematoda: Lepocreadiidae) and consideration of the related genus Pseudo or eadium. PMID- 21013421 TI - Redescription of the species of Gyrocotyle from the ratfish, Hydrolagus colliei (Lay and Bennet), with notes on the morphology and taxonomy of the genus. PMID- 21013422 TI - [Not Available]. PMID- 21013423 TI - [Not Available]. PMID- 21013424 TI - [Not Available]. PMID- 21013425 TI - The alkylation of alkanes. PMID- 21013426 TI - The chemistry of the oxazoles. PMID- 21013427 TI - The chemistry of oxindole. PMID- 21013428 TI - Synthetic estrogens and the relation between their structure and their activity. PMID- 21013429 TI - Attempts to find new antimalarials; amino alcohols derived from 1,2,3,4 tetrahydrophenanthrene. PMID- 21013430 TI - Attempts to find new antimalarials; amino alcohols derived from phenanthrene. PMID- 21013431 TI - Attempts to find new antimalarials; amino alcohols derived from 3 methoxyphenanthrene. PMID- 21013432 TI - Substitute alpha-dialkylaminoalkyl-l-naphthalenemethanols; amino ketone method. PMID- 21013433 TI - Substituted alpha-dialkylaminoalkyl-l-naphthalenemethanols; 1-halonaphthalenes in the Friedel and Crafts reaction. PMID- 21013435 TI - Fusion syntheses of aryl polyacylglycosides. PMID- 21013434 TI - The synthesis of some indene and dihydronaphthalene derivatives related to stilbestrol. PMID- 21013436 TI - Some potassium amide-activated phenylations in liquid ammonia. PMID- 21013437 TI - The reaction of phenanthrene with ethyl diazoacetate. PMID- 21013438 TI - Arylamine-N-glycosides; arylamine-N-D-ribopyranosides and N-D-ribofuranosides. PMID- 21013439 TI - Arylamine-N-glycosides; arylamine-N-pentosides and complex salt formation studies. PMID- 21013441 TI - Methone derivatives of aldehydes. PMID- 21013440 TI - Arylamine N-glycosides; hydrolysis of arylamine-N-pentosides and the preparation of crystalline D-ribose. PMID- 21013442 TI - Synthetic antimalarials; beta-dialkylaminoethanols. PMID- 21013443 TI - The relationship between ramus height, dental height, and overbite. PMID- 21013444 TI - Diagnosis and treatment planning in orthodontics. PMID- 21013445 TI - On the diagnosis and treatment of distoclusion. PMID- 21013446 TI - Supportive therapy in oral surgery. PMID- 21013447 TI - Essentials for successful root resection. PMID- 21013448 TI - Principles and technique of the removal of molar teeth. PMID- 21013449 TI - The mechanics of the temporomandibular joint: illustrated by two cases. PMID- 21013450 TI - Ankylosis of the temporomandibular joint. PMID- 21013452 TI - Cases of pathologic interest. PMID- 21013451 TI - Focal infection; a review of the recent literature. PMID- 21013453 TI - Dentigerous cysts. PMID- 21013454 TI - The odontomas; two case reports. PMID- 21013455 TI - [Not Available]. PMID- 21013457 TI - [Not Available]. PMID- 21013456 TI - [Not Available]. PMID- 21013458 TI - [Not Available]. PMID- 21013459 TI - [Not Available]. PMID- 21013460 TI - [Not Available]. PMID- 21013461 TI - [Not Available]. PMID- 21013462 TI - [Not Available]. PMID- 21013463 TI - [Not Available]. PMID- 21013464 TI - [Not Available]. PMID- 21013465 TI - Reactions of the hemopoietic system to agents used in the treatment of dermatoses; effects of low voltage roentgen ray therapy. PMID- 21013466 TI - Incidence of dermatoses in office practice in Hawaii. PMID- 21013467 TI - Recurrent, fixed erysipelas-like dermatophytid. PMID- 21013468 TI - Use of sulfated oil for cleansing the external auditory canal. PMID- 21013469 TI - Tyrothricin in cutaneous infections. PMID- 21013470 TI - Oxophenarsine hydrochloride in treatment of lupus erythematosus. PMID- 21013471 TI - Localized sensitivity to crude penicillin; report of a case. PMID- 21013472 TI - Treatment of dermatophytosis and hyperhidrosis with formaldehyde and cupric sulfate iontophoresis. PMID- 21013473 TI - Diffusion of water through dead plantar, palmar and torsal human skin and through toe nails. PMID- 21013474 TI - The adrenal glands in pemphigus vulgaris. PMID- 21013476 TI - Pityriasis rubra pilaris. PMID- 21013475 TI - Lupus erythematosus superimposed on a nevus. PMID- 21013477 TI - A case for diagnosis (psoriasis; parapsoriasis en plaques [Brock]. PMID- 21013478 TI - Tuberculoid leprosy. PMID- 21013479 TI - Morphea-like basal cell epithelioma with ulceration. PMID- 21013480 TI - Lupus erythematosus disseminatus (response to sulfadiazine?). PMID- 21013481 TI - Neural (early tuberculoid?) leprosy. PMID- 21013482 TI - Late cutaneous syphilis (gumma) with negative serologic reactions. PMID- 21013483 TI - Epidermolysis bullosa acquisita complicated by an annular vegetative iododerma. PMID- 21013484 TI - A case for diagnosis (poikiloderma?). PMID- 21013485 TI - A case for diagnosis (dermatitis herpetiformis?). PMID- 21013486 TI - Erythema annulare centrifugum. PMID- 21013487 TI - A case for diagnosis (ulerythema acneiforme?). PMID- 21013488 TI - Epidermolysis bullosa hereditaria. PMID- 21013489 TI - Necrobiosis lipoidica diabeticorum. PMID- 21013490 TI - Lupus erythematosus. PMID- 21013491 TI - Lymphoblastoma. PMID- 21013492 TI - Raynaud's disease; syphilis of the central nervous system. PMID- 21013493 TI - Tuberculosis cutis; lupus vulgaris; inactive osseous tuberculosis. PMID- 21013495 TI - A case for diagnosis (herpes simplex, recurrent; acne varioliformis?). PMID- 21013494 TI - A case for diagnosis (multiple hemorrhagic sarcoma of Kaposi; granuloma pyogenicum?). PMID- 21013496 TI - Acanthosis nigricans, benign type with acne and active duodenal ulcer. PMID- 21013497 TI - Acquired generalized anhidrosis with localized hyperhidrosis. PMID- 21013498 TI - A case for diagnosis (sarcoidosis? granuloma annulare?). PMID- 21013499 TI - A case for diagnosis (periarteritis nodosa?). PMID- 21013500 TI - A case for diagnosis (contact dermatitis; dermatitis medicamentosa?). PMID- 21013501 TI - A case for diagnosis (lupus erythematosus; papulonecrotic tuberculid?). PMID- 21013503 TI - Mycosis fungoides. PMID- 21013502 TI - Dermatitis herpetiformis of unusual type. PMID- 21013504 TI - Nevus unius lateris. PMID- 21013505 TI - Morphea. PMID- 21013506 TI - [Not Available]. PMID- 21013507 TI - [Not Available]. PMID- 21013509 TI - [Not Available]. PMID- 21013508 TI - [Not Available]. PMID- 21013510 TI - [Not Available]. PMID- 21013511 TI - [Not Available]. PMID- 21013512 TI - [Not Available]. PMID- 21013513 TI - [Not Available]. PMID- 21013514 TI - [Not Available]. PMID- 21013515 TI - [Not Available]. PMID- 21013516 TI - War bereavements and their recovery. PMID- 21013517 TI - Woman's role; the Catholic view. PMID- 21013518 TI - Sex education; a Catholic view. PMID- 21013520 TI - Community resources in teaching sex education. PMID- 21013519 TI - Education and guidance concerning human sex relations. PMID- 21013521 TI - Reflections on sex education in the high school. PMID- 21013522 TI - [Not Available]. PMID- 21013523 TI - [Not Available]. PMID- 21013524 TI - [Not Available]. PMID- 21013525 TI - [Not Available]. PMID- 21013526 TI - [Not Available]. PMID- 21013527 TI - [Not Available]. PMID- 21013528 TI - [Not Available]. PMID- 21013529 TI - [Not Available]. PMID- 21013530 TI - [Not Available]. PMID- 21013531 TI - [Not Available]. PMID- 21013532 TI - [Not Available]. PMID- 21013533 TI - [Not Available]. PMID- 21013534 TI - [Not Available]. PMID- 21013535 TI - [Not Available]. PMID- 21013536 TI - [Not Available]. PMID- 21013537 TI - [Not Available]. PMID- 21013539 TI - [Not Available]. PMID- 21013538 TI - [Not Available]. PMID- 21013540 TI - [Not Available]. PMID- 21013541 TI - [Not Available]. PMID- 21013542 TI - [Not Available]. PMID- 21013543 TI - [Not Available]. PMID- 21013544 TI - [Not Available]. PMID- 21013545 TI - Primary congenital and secondary acquired splenic panhematopenia. PMID- 21013546 TI - The megakaryocytes in idiopathic thrombocytopenic purpura, a form of hypersplenism. PMID- 21013547 TI - The value of penicillin in the treatment of agranulocytosis caused by thiouracil. PMID- 21013548 TI - Differentiation of pernicious anemia and certain other macrocytic anemias by the distribution of red blood cell diameters. PMID- 21013549 TI - The diagnosis of Hodgkin's disease by aspiration biopsy. PMID- 21013550 TI - [Not Available]. PMID- 21013551 TI - [Not Available]. PMID- 21013552 TI - [Not Available]. PMID- 21013554 TI - [Not Available]. PMID- 21013553 TI - [Not Available]. PMID- 21013555 TI - [Not Available]. PMID- 21013556 TI - [Not Available]. PMID- 21013557 TI - [Not Available]. PMID- 21013558 TI - INSECT transmission of leprosy. PMID- 21013559 TI - Preventoria; a symposium on the care of the children of leprous parents. PMID- 21013560 TI - Occupational therapy in leprosy institutions. PMID- 21013561 TI - Modes of transmission of Hansen's disease (leprosy). PMID- 21013562 TI - Palm oil in leprosy. PMID- 21013563 TI - The reaction of the pleura in primary tuberculosis of the lungs. PMID- 21013565 TI - [Not Available]. PMID- 21013564 TI - Excretion of urinary waste-products under abnormal conditions with special regard to tubular functions. PMID- 21013566 TI - Erythema nodosum following treatment with sulfanilamide compounds. PMID- 21013567 TI - [Not Available]. PMID- 21013569 TI - On the functional prolongation of the PQ time of the electrocardiogram. PMID- 21013568 TI - Examination of the tongue; a clinical and photographic study. PMID- 21013570 TI - The provocation factor in the pathogenesis of erythema nodosum; with special reference to a case of primary tuberculous infection in the skin. PMID- 21013571 TI - A special type of rheumatic disease. PMID- 21013572 TI - Case of leukemic myelomatosis (plasma cell leukemia). PMID- 21013573 TI - [Not Available]. PMID- 21013574 TI - Treatment of thyrotoxicosis with methylthiouracil. PMID- 21013575 TI - The influence of posture on the kidney function; the fall of the diuresis in the erect posture. PMID- 21013576 TI - The influence of posture on the kidney function; glomerular dynamics in the passive erect posture. PMID- 21013577 TI - The abnormal electrocardiogram; clinical significance of right axis deviation. PMID- 21013578 TI - [Not Available]. PMID- 21013579 TI - Meningococcus myocarditis; report of two cases with anatomical and clinical characteristics. PMID- 21013580 TI - Spontaneous pneumothorax in healthy young adults, with particular reference to the etiological role of aerial ascent. PMID- 21013581 TI - Why certified milk? PMID- 21013582 TI - Amino acids in the production of plasma protein and nitrogen balance. PMID- 21013583 TI - The effect of salicylate therapy on the Weltmann serum coagulation reaction and its use as a prognostic test in rheumatic fever. PMID- 21013585 TI - Thrombophlebitis with multiple pulmonary emboli; psychiatric self-observations. PMID- 21013584 TI - Psittacosis treated with sulfonamide drugs. PMID- 21013586 TI - Thiouracil effect in diabetes mellitus complicated by hyperthyroidism. PMID- 21013587 TI - The influence of environmental temperature and relative humidity on the rate of water loss through the skin in congestive heart failure in a subtropical climate. PMID- 21013588 TI - The respiratory quotient and blood pyruvate and lactate responses after oral ingestion of glucose and fructose in diabetes mellitus with and without insulin. PMID- 21013589 TI - Human utilization of biotin from various diets. PMID- 21013590 TI - Chloroma, a clinico-pathologic study of two cases. PMID- 21013591 TI - The natural course of chronic southwest Pacific malaria. PMID- 21013592 TI - Electrocardiographic evidence of cardiac complications in infectious mononucleosis. PMID- 21013593 TI - The treatment of human hypertension with a kidney extract. PMID- 21013594 TI - A review of the present concepts on fluid balance. PMID- 21013595 TI - Retinal lesions in acute disseminate lupus erythematosis. PMID- 21013596 TI - The effect of the alkyl sulfates on gastric secretion in the rat. PMID- 21013597 TI - Observations on an oligodynamic action of copper on human erythrocytes. PMID- 21013598 TI - War and tuberculosis. PMID- 21013599 TI - The organization of anti-tuberculosis work. PMID- 21013600 TI - The immunizing value of the BGG dry glucose vaccine. PMID- 21013601 TI - Employment during pneumothorax for tubercular patients. PMID- 21013602 TI - The mechanism of antiviral immunity; the role of leukocytes in immunity to the viruses of infectious ectromelia and herpes. PMID- 21013603 TI - The innervation of the heart. PMID- 21013604 TI - Restoration of regular rhythm in the mammalian fibrillating heart. PMID- 21013605 TI - The struggle against fungus diseases in the Turkmenian SSR. PMID- 21013606 TI - Re-establishment of circulation, respiration, and functions of the central nervous system in new born dying from asphyxia. PMID- 21013607 TI - A review of Soviet cardiology. PMID- 21013608 TI - Effect of a daily vitamin supplement on the health and development of children. PMID- 21013609 TI - Effect of blast on the human ear. PMID- 21013610 TI - The hippuric acid test in pregnancy. PMID- 21013611 TI - Sulphapyridine anuria in Gurkhas. PMID- 21013612 TI - Acute pancreatitis. PMID- 21013613 TI - A fatality from thyroidectomy following a leucopenia caused by thiouracil. PMID- 21013614 TI - Palindromic rheumatism. PMID- 21013616 TI - Mitral regurgitation. PMID- 21013615 TI - Occupational eye diseases. PMID- 21013617 TI - Galvanic stimulation of denervated muscle. PMID- 21013618 TI - Nicotinic acid amide in diabetes. PMID- 21013619 TI - Diagnosis and management of common pulmonary diseases. PMID- 21013620 TI - The early diagnosis of pulmonary tuberculosis. PMID- 21013621 TI - The general treatment of pulmonary tuberculosis. PMID- 21013622 TI - Artificial pneumothorax and other collapse therapy in pulmonary tuberculosis. PMID- 21013623 TI - Rehabilitation of the tuberculous. PMID- 21013624 TI - Spontaneous hemopneumothorax. PMID- 21013625 TI - Bronchiectasis. PMID- 21013626 TI - Pulmonary mycoses. PMID- 21013627 TI - Primary lung tumors; a plea for early diagnosis. PMID- 21013628 TI - Placenta previa and premature separation of the normally situated placenta. PMID- 21013629 TI - Alcohol. PMID- 21013630 TI - [Not Available]. PMID- 21013631 TI - [Not Available]. PMID- 21013632 TI - [Not Available]. PMID- 21013634 TI - [Not Available]. PMID- 21013633 TI - [Not Available]. PMID- 21013635 TI - [Not Available]. PMID- 21013636 TI - [Not Available]. PMID- 21013637 TI - [Not Available]. PMID- 21013638 TI - [Not Available]. PMID- 21013639 TI - [Not Available]. PMID- 21013640 TI - [Not Available]. PMID- 21013641 TI - [Not Available]. PMID- 21013642 TI - [Not Available]. PMID- 21013643 TI - [Not Available]. PMID- 21013644 TI - [Not Available]. PMID- 21013645 TI - [Not Available]. PMID- 21013646 TI - [Not Available]. PMID- 21013647 TI - [Not Available]. PMID- 21013648 TI - [Not Available]. PMID- 21013649 TI - [Not Available]. PMID- 21013650 TI - [Not Available]. PMID- 21013651 TI - [Not Available]. PMID- 21013652 TI - [Not Available]. PMID- 21013653 TI - Primary lung tumors. PMID- 21013654 TI - Hypoglycemic fatigue. PMID- 21013655 TI - The treatment of agranulocytosis with penicillin. PMID- 21013656 TI - The teaching of drug therapy. PMID- 21013657 TI - Penicillin for ulcers of leg treated by pinch grafts. PMID- 21013658 TI - Effect of tridione in the control of psychomotor attacks. PMID- 21013659 TI - Rubella in pregnancy causing malformations in newborn. PMID- 21013660 TI - Complete subsidence of scleroderma with dihydrotachysterol. PMID- 21013661 TI - [Not Available]. PMID- 21013662 TI - [Not Available]. PMID- 21013663 TI - [Not Available]. PMID- 21013665 TI - [Not Available]. PMID- 21013664 TI - [Not Available]. PMID- 21013666 TI - [Not Available]. PMID- 21013667 TI - [Not Available]. PMID- 21013668 TI - [Not Available]. PMID- 21013669 TI - [Not Available]. PMID- 21013670 TI - [Not Available]. PMID- 21013671 TI - Occupational dermatitis. PMID- 21013672 TI - Pathologic aspects of certain surgical diseases of the stomach and duodenum. PMID- 21013673 TI - Surgical treatment of intestinal obstruction; preoperative preparation. PMID- 21013674 TI - The Tulsa County Medical Clinic. PMID- 21013675 TI - Rheumatic fever in children. PMID- 21013676 TI - Roentgen diagnosis in heart disease. PMID- 21013678 TI - Congestive heart failure. PMID- 21013677 TI - Paroxysmal cardiac irregularities. PMID- 21013679 TI - [The treatment and prophylaxis of septic puerperal illnesses with massive doses of various sulfamide preparations]. PMID- 21013680 TI - [Hypoproteinemia and wound emaciation]. PMID- 21013681 TI - [The clinics of wounds of the lungs and pleura]. PMID- 21013682 TI - [On vegetative-vascular disorders]. PMID- 21013683 TI - [Disturbances of metabolism in connection with closed traumae of the cranium]. PMID- 21013684 TI - [On changes in alkali reserve in traumatic shock in men]. PMID- 21013687 TI - [The clinics of disturbances of the blood circulation in the vessels of the mesentery in relation to thrombosis and emboli]. PMID- 21013686 TI - [The blood proteins and their dynamics in suppurative processes]. PMID- 21013685 TI - [Calculi formation in the urinary system in connection with war traumae]. PMID- 21013688 TI - [Contribution to the compensatory factors of the oxidation processes in the organism in anemias]. PMID- 21013689 TI - [On the clinics and therapy of spring-estival tick encephalitis]. PMID- 21013690 TI - [On the clinics and diagnosis of the atypical forms of infarction of the myocardium]. PMID- 21013691 TI - [On the connection between the dosage, concentration in the blood and the therapeutic effect of sulfidine in the treatment of pneumonia]. PMID- 21013692 TI - [On the toxic phenomena and complications of sulfidine therapy]. PMID- 21013693 TI - [The rectal method of sulfidine infusion in lobar pneumonia]. PMID- 21013694 TI - [Contribution to the comparative efficiency of sulfidine under various methods of its infusion]. PMID- 21013695 TI - [Concerning the intravenous use of sulfidine]. PMID- 21013696 TI - [Intravenous method of the treatment of pneumonia]. PMID- 21013697 TI - Chemotherapy of pneumococcal meningitis. PMID- 21013698 TI - Tubercle bacilli in the pleural effusion of young adults. PMID- 21013699 TI - Criteria of eosinophilia. PMID- 21013700 TI - Nutritive values of wheat flours of different extraction rate. PMID- 21013701 TI - Outbreak of polyneuritis due to orthotricresyl phosphate poisoning. PMID- 21013702 TI - ABORTION for probable defects in the child. PMID- 21013703 TI - SALARIED specialist; work and pay. PMID- 21013704 TI - Control of Sonne dysentery. PMID- 21013705 TI - [Not Available]. PMID- 21013706 TI - [Not Available]. PMID- 21013707 TI - [Not Available]. PMID- 21013708 TI - [Not Available]. PMID- 21013709 TI - [Not Available]. PMID- 21013710 TI - [Not Available]. PMID- 21013711 TI - [Not Available]. PMID- 21013712 TI - [Not Available]. PMID- 21013713 TI - [Not Available]. PMID- 21013714 TI - [Not Available]. PMID- 21013715 TI - [Not Available]. PMID- 21013716 TI - [Not Available]. PMID- 21013717 TI - [Not Available]. PMID- 21013719 TI - [Not Available]. PMID- 21013718 TI - [Not Available]. PMID- 21013720 TI - Literature and the clinical point of view. PMID- 21013721 TI - A report on the transfusion of 2,386 litres of blood. PMID- 21013722 TI - The Rh factor: a survey of the sub-types of white Australians. PMID- 21013723 TI - The administration of penicillin. PMID- 21013724 TI - A preliminary note on the cultivation in vitro of New Guinea strains of human malarial parasites. PMID- 21013725 TI - Blast effects complicating abdominal injuries. PMID- 21013726 TI - Some further observations on sciatica. PMID- 21013727 TI - Sciatica. PMID- 21013728 TI - Low back pain. PMID- 21013729 TI - Low backache. PMID- 21013730 TI - Low backache. PMID- 21013731 TI - Recent advances in the diagnosis and treatment of lumbar intervertebral disk disease. PMID- 21013732 TI - Recent advances in the surgical treatment of lumbar intervertebral disk disease. PMID- 21013733 TI - INTERVERTEBRAL disk. PMID- 21013734 TI - SCIATICA. PMID- 21013735 TI - Pyloric obstruction without tumour. PMID- 21013736 TI - Adrenal carcinoma causing precocity. PMID- 21013737 TI - Politics and the medical profession. PMID- 21013738 TI - A case of so-called hydrophobia; a matter of diagnosis. PMID- 21013739 TI - Some effects of blood loss on healthy males. PMID- 21013740 TI - Early results of the treatment of gunshot wounds of limb joints aided by penicillin therapy. PMID- 21013741 TI - The use of polysaccharide of bacillus proteus OXK in the diagnosis of scrub typhus. PMID- 21013742 TI - The post-war rehabilitation of science. PMID- 21013743 TI - A sociological study of the aborigines in the Northern Territory and their eye diseases. PMID- 21013744 TI - Traumatic arterio-venous aneurysm of the femoral blood vessels. PMID- 21013745 TI - Putrid lung abcess. PMID- 21013746 TI - Inguinal hernia and its repair. PMID- 21013748 TI - Transposition of viscera. PMID- 21013747 TI - An immune anti-M iso-agglutinin in human serum. PMID- 21013749 TI - Present status of electric sleep treatments. PMID- 21013750 TI - Heart failure; diagnosis, prognosis and treatment. PMID- 21013751 TI - A new conception of diaphragmatic hernia. PMID- 21013752 TI - The radical operation for carcinoma of the rectosigmoid. PMID- 21013753 TI - The value of radium in various diseases. PMID- 21013755 TI - Psychology of friendship and acquaintanceship. PMID- 21013754 TI - Tinnitus aurium, dizziness and deafness. PMID- 21013756 TI - Reflections on a study of the performance of a group of women physicians. PMID- 21013757 TI - The RH factor in feeble-mindedness and other diseases. PMID- 21013758 TI - Serology and obstetrics. PMID- 21013759 TI - The bedside diagnosis of liver disease. PMID- 21013760 TI - Kerion; a review. PMID- 21013761 TI - Ureteral obstruction caused by aneurysm of the iliac artery. PMID- 21013762 TI - Experiences in an evacuation hospital in ETO. PMID- 21013763 TI - Calculation of disability in the extremities. PMID- 21013764 TI - Pregnancy complicated by idiopathic thrombocytopenic purpura and sarcoid disease of the spleen; splenectomy and subsequent normal delivery. PMID- 21013765 TI - Reflections on the development and present general application of acrylic to conservative procedures. PMID- 21013766 TI - Discussion on surgery of the patent ductus arteriosus (infected and uninfected). PMID- 21013767 TI - Acute rheumatism in military history. PMID- 21013768 TI - Cardiac folk-lore. PMID- 21013770 TI - Pulmonary haemosiderosis. PMID- 21013771 TI - Refractory anaemia. PMID- 21013769 TI - Non-specific intestinal granuloma. PMID- 21013772 TI - Nephrocalcinosis associated with hyperchloraemia. PMID- 21013773 TI - Two cases of Banti's syndrome: hepatomegaly with anaemia. PMID- 21013774 TI - Two cases of Ehlers-Danlos syndrome. PMID- 21013775 TI - Forward psychiatry in the Army. PMID- 21013776 TI - Discussion on the importance of diet in mental-illness. PMID- 21013777 TI - A simple method for the concentration of Rh agglutinins. PMID- 21013778 TI - Results of inoculating Okinawan horses with the virus of Japanese B encephalitis. PMID- 21013779 TI - Relationship of carotid and aortic mechanisms to digitalis emesis. PMID- 21013780 TI - The electron micrography of plant virus-antibody mixtures. PMID- 21013781 TI - The effect of lecithin administered intravenously. PMID- 21013782 TI - In vitro susceptibility of Histoplasma capsulatum to therapeutic agents. PMID- 21013783 TI - Effect of large doses of streptomycin and influenza viruses on chick embryos. PMID- 21013784 TI - Protection of mice against lethal action of gonococcal endotoxin by penicillin. PMID- 21013786 TI - A method for removal of adult S. mansoni from experimentally infected rabbits. PMID- 21013785 TI - Action of anterior pituitary on Sertoli cells and on release of toad spermatozoa. PMID- 21013787 TI - Subtilin, antibiotic produced by Bacillus subtilis; toxicity of subtilin to living embryonic tissue. PMID- 21013788 TI - Amyloidosis in hamsters with leishmaniasis. PMID- 21013789 TI - Occurrence of two immunological groups within the genus Listeria; studies based upon precipitation reactions. PMID- 21013790 TI - Changes in weight of muscles of arthritic and immobilized arthritic joints. PMID- 21013791 TI - Respiratory mask and valves for dogs. PMID- 21013792 TI - Effect of salicylate on plasma fibrinogen and sedimentation rate in rheumatic and non-rheumatic patients. PMID- 21013793 TI - A test for penicillin sensitivity and resistance in Staphylococcus. PMID- 21013795 TI - Effect of nutrition on susceptibility of mice to pneumococcal infection. PMID- 21013794 TI - Effect of anesthetics and convulsants on brain acetylcholine content. PMID- 21013796 TI - Further purification of the follicle stimulating hormone and its effect in normal and hypophysectiomized rats. PMID- 21013797 TI - Urinary excretion of estrogens and 17-ketosteroids in young, adult males with infectious hepatitis. PMID- 21013798 TI - Adequacy of the known synthetic vitamins for normal feathering and pigmentation in chicks. PMID- 21013799 TI - Effect of radon-containing ointment on cutaneous lymph flow and minute vessels of skin. PMID- 21013800 TI - Effects of glutathione and thioglycollic acid on acid-production by Lactobacillus arabinosus in presence of atabrine. PMID- 21013801 TI - Lactation leucopenia in rats on purified diets. PMID- 21013802 TI - Identification of rickettsial agents isolated in guinea pigs by means of specific complement fixation. PMID- 21013803 TI - Studies on chancroid; the Ducrey bacillus; growth requirements and inhibition by antibiotic agents. PMID- 21013804 TI - Muscles consisting of a single motor unit after poliomyelitis. PMID- 21013805 TI - Development of Brucella agglutinins in humans following vaccination for cholera. PMID- 21013806 TI - Excitability of muscle to direct and indirect stimulation during prolonged direct stimulation. PMID- 21013807 TI - Folic acid active compounds in the nutrition of the monkey. PMID- 21013808 TI - A differential, microbiological assay for O-heterobiotin. PMID- 21013809 TI - [Not Available]. PMID- 21013810 TI - [Not Available]. PMID- 21013811 TI - [Not Available]. PMID- 21013812 TI - [Not Available]. PMID- 21013813 TI - [Not Available]. PMID- 21013814 TI - The challenge of thrombosis and embolism of blood vessels, and the clinical use of anticoagulants. PMID- 21013815 TI - Graduate medical education. PMID- 21013816 TI - Late recurrence in the skin following radical amputation of the breast for carcinoma. PMID- 21013817 TI - Pellagra, a study in human nutrition; the multiple-factor principle of the determination of minimum vitamin requirements. PMID- 21013818 TI - A rare case of lead poisoning. PMID- 21013819 TI - The letters and libraries of Irving S. Cutter and Harvey Cushing. PMID- 21013820 TI - The function of the library in a medical school. PMID- 21013821 TI - Via optica. PMID- 21013822 TI - Bilateral primary sarcoma of the kidney. PMID- 21013823 TI - A perspective of biochemical defects in muscle in vitamin E deficiency. PMID- 21013824 TI - Evaluation of blood sugar tests. PMID- 21013825 TI - Biographical notes regarding some American military surgeons. PMID- 21013826 TI - A study of the effect on the prothrombin time of the drugs more commonly used in cardiovascular diseases. PMID- 21013827 TI - The role of thiamin deficiency in heart disease with failure. PMID- 21013828 TI - Blood pressure and life insurance. PMID- 21013829 TI - Adventurous physicians. PMID- 21013830 TI - Beware of vitamins. PMID- 21013831 TI - War and psychosomatic disease. PMID- 21013832 TI - Liquid ammonia and the nitrogen system of compounds. PMID- 21013833 TI - Pulmonary hypertension and corpulmonale. PMID- 21013834 TI - The relation of chemical structure to biologic activity. PMID- 21013836 TI - Erythroblastosis fetalis and the rhesus factor. PMID- 21013835 TI - The relation of chemical structure to biologic activity. PMID- 21013837 TI - [Not Available]. PMID- 21013838 TI - [Not Available]. PMID- 21013839 TI - [Not Available]. PMID- 21013840 TI - [Not Available]. PMID- 21013841 TI - [Not Available]. PMID- 21013842 TI - [Not Available]. PMID- 21013843 TI - [Not Available]. PMID- 21013844 TI - [Not Available]. PMID- 21013845 TI - [Not Available]. PMID- 21013847 TI - [Not Available]. PMID- 21013846 TI - [Not Available]. PMID- 21013848 TI - [Not Available]. PMID- 21013849 TI - [Not Available]. PMID- 21013850 TI - [Not Available]. PMID- 21013851 TI - [Not Available]. PMID- 21013852 TI - [Not Available]. PMID- 21013853 TI - [Not Available]. PMID- 21013854 TI - [Not Available]. PMID- 21013855 TI - [Not Available]. PMID- 21013856 TI - [Not Available]. PMID- 21013857 TI - [Not Available]. PMID- 21013858 TI - [Not Available]. PMID- 21013860 TI - [Not Available]. PMID- 21013859 TI - [Not Available]. PMID- 21013861 TI - [Not Available]. PMID- 21013862 TI - [Not Available]. PMID- 21013863 TI - [Not Available]. PMID- 21013864 TI - [Not Available]. PMID- 21013865 TI - [Not Available]. PMID- 21013866 TI - [Not Available]. PMID- 21013867 TI - [Not Available]. PMID- 21013868 TI - [Not Available]. PMID- 21013869 TI - [Not Available]. PMID- 21013870 TI - [Not Available]. PMID- 21013871 TI - [Not Available]. PMID- 21013872 TI - [Not Available]. PMID- 21013873 TI - [Not Available]. PMID- 21013875 TI - [Not Available]. PMID- 21013874 TI - [Not Available]. PMID- 21013876 TI - [Not Available]. PMID- 21013877 TI - [Not Available]. PMID- 21013878 TI - [Not Available]. PMID- 21013879 TI - [Not Available]. PMID- 21013880 TI - [Not Available]. PMID- 21013881 TI - [Not Available]. PMID- 21013882 TI - [Not Available]. PMID- 21013883 TI - [Not Available]. PMID- 21013884 TI - [Not Available]. PMID- 21013885 TI - [Not Available]. PMID- 21013886 TI - [Not Available]. PMID- 21013887 TI - [Not Available]. PMID- 21013888 TI - [Not Available]. PMID- 21013889 TI - [Not Available]. PMID- 21013890 TI - [Not Available]. PMID- 21013891 TI - [Not Available]. PMID- 21013892 TI - [Not Available]. PMID- 21013893 TI - [Not Available]. PMID- 21013894 TI - [Not Available]. PMID- 21013895 TI - [Not Available]. PMID- 21013896 TI - [Not Available]. PMID- 21013898 TI - [Not Available]. PMID- 21013897 TI - [Not Available]. PMID- 21013899 TI - [Not Available]. PMID- 21013900 TI - [Not Available]. PMID- 21013901 TI - [Not Available]. PMID- 21013902 TI - [Not Available]. PMID- 21013903 TI - [Not Available]. PMID- 21013904 TI - [Not Available]. PMID- 21013905 TI - [Not Available]. PMID- 21013906 TI - [Not Available]. PMID- 21013907 TI - [Not Available]. PMID- 21013908 TI - [Not Available]. PMID- 21013909 TI - [Not Available]. PMID- 21013910 TI - [Not Available]. PMID- 21013911 TI - [Not Available]. PMID- 21013912 TI - [Not Available]. PMID- 21013913 TI - [Not Available]. PMID- 21013915 TI - [Not Available]. PMID- 21013914 TI - [Not Available]. PMID- 21013916 TI - [Not Available]. PMID- 21013917 TI - [Not Available]. PMID- 21013918 TI - [Not Available]. PMID- 21013919 TI - [Not Available]. PMID- 21013920 TI - [Not Available]. PMID- 21013921 TI - [Not Available]. PMID- 21013922 TI - [Not Available]. PMID- 21013923 TI - [Not Available]. PMID- 21013924 TI - [Not Available]. PMID- 21013925 TI - [Not Available]. PMID- 21013926 TI - [Not Available]. PMID- 21013927 TI - [Not Available]. PMID- 21013928 TI - [Not Available]. PMID- 21013929 TI - [Not Available]. PMID- 21013930 TI - OUTBREAKS of a rickettsial disease related to Q fever. PMID- 21013931 TI - Hookworm in troops returning from the Pacific. PMID- 21013933 TI - SMALLPOX appears again. PMID- 21013932 TI - LYMPHADENOPATHY and filariasis. PMID- 21013934 TI - EFFECT of antiseptics on the regeneration of corneal epithelium. PMID- 21013935 TI - EXCRETION of lesser known vitamin B complex vitamins during restricted intake. PMID- 21013936 TI - NUTRITION in Japan. PMID- 21013937 TI - RESEARCH on dental caries. PMID- 21013938 TI - DEVICE FOR folding surgical sponges. PMID- 21013940 TI - DANGEROUS carriers of hemolytic streptococci and their control. PMID- 21013939 TI - EFFECTS OF strategic bombing on Germany's health. PMID- 21013941 TI - Battle injuries of the arteries in World War II. PMID- 21013942 TI - The future of physical medicine. PMID- 21013943 TI - Dengue-like fever on Okinawa. PMID- 21013944 TI - Incidence of testicular pathology. PMID- 21013945 TI - Hypnosis as a therapeutic technique in the war neuroses. PMID- 21013946 TI - Use of whole blood in a field hospital. PMID- 21013947 TI - The neurosurgical service in an evacuation hospital. PMID- 21013949 TI - Recovery from severe hypoplastic anemia associated with atypical lichen planus. PMID- 21013948 TI - Effect of the antimony compounds, fuadin and tartar emetic, on the electrocardiogram; a preliminary report. PMID- 21013950 TI - Therapy unit for patients with skin diseases. PMID- 21013951 TI - Salmonella epidemic from commercially prepared sandwiches. PMID- 21013952 TI - Outbreak of cadmium poisoning. PMID- 21013953 TI - Investigation of outbreaks of food poisoning. PMID- 21013954 TI - Disposition section for ambulatory patients. PMID- 21013955 TI - Immobilizing device for skull radiography. PMID- 21013956 TI - Laceration of inferior vena cava requiring ligation. PMID- 21013957 TI - A poison-squirting spider. PMID- 21013958 TI - Adaptable grid holder. PMID- 21013959 TI - Anthrax treated with sulfadiazine; report of a case. PMID- 21013960 TI - Uveitis with secondary glaucoma; report of case. PMID- 21013961 TI - Immovilization of the irreparably injured shoulder joint. PMID- 21013962 TI - The Navy hospital corpsmen. PMID- 21013964 TI - PLASTIC surgery. PMID- 21013963 TI - Powder packs for treatment of fungus. PMID- 21013965 TI - The Solace in action. PMID- 21013966 TI - Civil readjustment in naval hospitals. PMID- 21013967 TI - Temporary denture repair. PMID- 21013968 TI - [Not Available]. PMID- 21013969 TI - [Not Available]. PMID- 21013970 TI - [Not Available]. PMID- 21013971 TI - [Not Available]. PMID- 21013972 TI - [Not Available]. PMID- 21013973 TI - Reaction of periodic acid on the difructose anhydrides. PMID- 21013974 TI - Ultraviolet spectra and dissociation constants of p-hydroxybenzoic acid, methyl, ethyl, n-butyl, and benzyl p-hydroxybenzoate and potassium p-phenolsulfonate. PMID- 21013975 TI - First dissociation constant of o-phthalic acid and related pHvalues of phthalate buffers from 0 degrees to 60 degrees C. PMID- 21013977 TI - Documentary reproduction. PMID- 21013976 TI - INTERNATIONAL Genetics Conference. PMID- 21013978 TI - Rh gene frequencies in Britain. PMID- 21013979 TI - A new mutant of Saccharomyces cerevisiae. PMID- 21013980 TI - Peculiar cytological behaviour of a distillery yeast. PMID- 21013981 TI - A specific effect of high-frequency electric currents on biological objects. PMID- 21013982 TI - Recent genetical experiments with yeasts. PMID- 21013983 TI - Haemoglobin levels in Britain. PMID- 21013985 TI - Pectin intravenously. PMID- 21013984 TI - Science and man's dilemma. PMID- 21013986 TI - Water loss from the respiratory tract in the subtropics. PMID- 21013987 TI - Recent contributions to the theory of random functions. PMID- 21013988 TI - Blood group factors and ethnic relationships. PMID- 21013989 TI - [Not Available]. PMID- 21013990 TI - [Not Available]. PMID- 21013991 TI - [Not Available]. PMID- 21013992 TI - [Not Available]. PMID- 21013993 TI - [Not Available]. PMID- 21013994 TI - [Not Available]. PMID- 21013995 TI - [Not Available]. PMID- 21013996 TI - [Not Available]. PMID- 21013997 TI - [Not Available]. PMID- 21013998 TI - [Not Available]. PMID- 21013999 TI - [Not Available]. PMID- 21014000 TI - Anxiety, phobias, and fears in young children, with special reference to prenatal, natal, and neonatal factors. PMID- 21014001 TI - Orthogenesis of anxiety. PMID- 21014002 TI - Neurotic anxieties in children and their prevention. PMID- 21014003 TI - Early fears and early defences; selected problems. PMID- 21014004 TI - The persecuted child. PMID- 21014005 TI - Some factors aiding the development of security in the institutional child. PMID- 21014006 TI - [Not Available]. PMID- 21014007 TI - [Not Available]. PMID- 21014008 TI - [Not Available]. PMID- 21014009 TI - The patient and his needs. PMID- 21014010 TI - Nasal catarrh; prevention, symptoms and nursing treatment. PMID- 21014011 TI - Recent advances in disinfestation; D.D.T. in social welfare work. PMID- 21014013 TI - Drug treatment of constipation. PMID- 21014012 TI - Common skin disorders of children. PMID- 21014014 TI - Hospital or guest house? PMID- 21014015 TI - Orthopaedic nursing. PMID- 21014016 TI - Recent advances in disinfestation; insecticides and insect repellents. PMID- 21014017 TI - Rare diseases of returning service men; pellagra. PMID- 21014018 TI - Syringe jaundice; importance of thorough sterilisation of syringes. PMID- 21014019 TI - Rare diseases of returning service men; ancylostomiasis. PMID- 21014020 TI - Nursing care following laryngectomy. PMID- 21014021 TI - Recruitment and training of nurses. PMID- 21014023 TI - Training of nurses in hospital. PMID- 21014022 TI - Hormones in human reproduction; oestrin. PMID- 21014024 TI - Surgical ligatures and sutures. PMID- 21014025 TI - Rare diseases of returning service men; schistosomiasis. PMID- 21014026 TI - Hormones in human reproduction; progesterone. PMID- 21014027 TI - A study of astigmatism at the near point with special reference to astigmatic accommodation. PMID- 21014028 TI - Notes on the hygiene of the refracting room. PMID- 21014029 TI - A suggested dynamic subjective test. PMID- 21014030 TI - Policy on contact lens fitting as adopted by the Indiana Association of Optometrists. PMID- 21014031 TI - Occurrence of glioma of retina and brain in collateral lines in same family; genetics of glioma. PMID- 21014032 TI - Injection of oxygen into Tenon's capsule. PMID- 21014033 TI - Clinical study of effect of tobacco on the normal angioscotoma. PMID- 21014034 TI - Cyclodiathermy in treatment of glaucoma due to rubeosis iridis diabetica. PMID- 21014035 TI - Oculomotor paralysis with partial recovery; report of a case. PMID- 21014036 TI - Congenital retinal fold. PMID- 21014037 TI - Intraocular penetration of streptomycin following systemic and local administration. PMID- 21014038 TI - Congenital cataract and other anomalies following rubella in mother during pregnancy; a California survey. PMID- 21014039 TI - Ocular imagery. PMID- 21014040 TI - Retinal venous thrombosis following reaction to vaccine. PMID- 21014041 TI - Corneal punch for square and rectangular transplantations of cornea. PMID- 21014042 TI - Ocular complications of malaria. PMID- 21014043 TI - Review of the literature of 1945 pertaining to bronchoesophagology. PMID- 21014044 TI - Temporary deafness following exposure to loud tones and noise. PMID- 21014045 TI - Management of fractures into the nasal sinuses. PMID- 21014046 TI - The value of individual hearing aids for hard of hearing children in public schools; report to the sub-committee of the Committee on Problems of Deafness of the National Research Council; the otological examination and follow up. PMID- 21014047 TI - [Not Available]. PMID- 21014048 TI - [Not Available]. PMID- 21014050 TI - [Not Available]. PMID- 21014049 TI - [Not Available]. PMID- 21014051 TI - [Not Available]. PMID- 21014052 TI - [Not Available]. PMID- 21014053 TI - [Not Available]. PMID- 21014054 TI - [Not Available]. PMID- 21014055 TI - [Not Available]. PMID- 21014056 TI - [Not Available]. PMID- 21014057 TI - Absorption of scar tissue in experimental nodular cirrhosis of the liver, with a method of visualizing cirrhotic changes. PMID- 21014058 TI - Microscopic lesions in acetylcholine shock. PMID- 21014059 TI - Relation of cholelithiasis to acute hemorrhagic pancreatitis. PMID- 21014060 TI - Experimental pituitary diabetes of five years' duration with glomerulosclerosis. PMID- 21014061 TI - Morphologic studies of rats deprived of essential amino acids; histidine. PMID- 21014062 TI - Occurrence of rheumatic carditis in the native population of Curacao, Netherlands West Indies. PMID- 21014063 TI - Fat necrosis studies; the effect of feeding lipase-containing vegetable seed on the production of fat necrosis. PMID- 21014064 TI - Experimental nephropathies; glycosuria in dogs poisoned with uranyl nitrate, mercury bichloride and potassium dichromate. PMID- 21014066 TI - Obstruction of the aortic isthmus by a calcified thrombus. PMID- 21014065 TI - Leukopenia and inflammation; the presence of a leukopenic factor in inflammatory exudates. PMID- 21014067 TI - Tropical disease; involvement of the nervous system. PMID- 21014068 TI - [Not Available]. PMID- 21014069 TI - [Not Available]. PMID- 21014070 TI - [Not Available]. PMID- 21014071 TI - [Not Available]. PMID- 21014072 TI - [Not Available]. PMID- 21014073 TI - [Not Available]. PMID- 21014075 TI - What mothers think about day care. PMID- 21014074 TI - [Not Available]. PMID- 21014076 TI - Protection of mothers and children in Peru. PMID- 21014077 TI - SOCIAL workers look at adoption. PMID- 21014078 TI - Helping the hard-of-hearing child. PMID- 21014079 TI - [Not Available]. PMID- 21014080 TI - [Not Available]. PMID- 21014081 TI - [Not Available]. PMID- 21014083 TI - [Not Available]. PMID- 21014082 TI - [Not Available]. PMID- 21014084 TI - [Not Available]. PMID- 21014085 TI - [Not Available]. PMID- 21014086 TI - [Not Available]. PMID- 21014087 TI - [Not Available]. PMID- 21014088 TI - [Not Available]. PMID- 21014089 TI - [Not Available]. PMID- 21014090 TI - [Not Available]. PMID- 21014091 TI - [Not Available]. PMID- 21014092 TI - [Not Available]. PMID- 21014093 TI - [Not Available]. PMID- 21014094 TI - [Not Available]. PMID- 21014095 TI - [Not Available]. PMID- 21014096 TI - [Not Available]. PMID- 21014097 TI - [Not Available]. PMID- 21014098 TI - The psychology of learning from demonstration films. PMID- 21014099 TI - Personality adjustments of ninth-grade pupils as measured by the multiple choice Rorschach test and the California test of personality. PMID- 21014100 TI - The effect of bilingualism upon the measurement of the intelligence of children of preschool age. PMID- 21014101 TI - The effect of a measure of interest factors on the prediction of performance in a college social sciences comprehensive examination. PMID- 21014102 TI - On the interpretation of the correlation coefficient as a measure of predictive efficiency. PMID- 21014103 TI - Motivation in occupational choice among junior-senior high school students. PMID- 21014104 TI - The effect of pre-first-grade training upon reading readiness and reading achievement among Spanish-American children. PMID- 21014105 TI - Up through the years. PMID- 21014106 TI - Forty years in an institution. PMID- 21014107 TI - The prevalence of endemic typhus fever in Florida. PMID- 21014109 TI - Miami's manner of rodent control. PMID- 21014108 TI - The rodent control program of the Hillsborough County Health Department. PMID- 21014110 TI - Typhus control, Leon County Health Department. PMID- 21014111 TI - Rat control in the City of Jacksonville, Florida. PMID- 21014112 TI - Factors bearing on infant mortality in an industrial town. PMID- 21014113 TI - Mental deficiency in the past. PMID- 21014114 TI - Pulmonary tuberculosis in wartime. PMID- 21014115 TI - The increase in tuberculosis proportionate mortality among nonwhite young adults. PMID- 21014116 TI - Negro mortality; mortality from all causes in the death registration states. PMID- 21014117 TI - [The treatment of non-closing wounds, ulcers and contractures by grafting of chemically treated tissue, after Krause]. PMID- 21014118 TI - [On a new biological method of the treatment of wounds]. PMID- 21014119 TI - [Complications of wounds in scurvy]. PMID- 21014120 TI - [Injuries resulting from traffic accidents after the data of the Kuibyshev Hospital (Leningrad)]. PMID- 21014121 TI - [Employment of transudation as a fluid substituent for blood in the treatment of wounded and other patients]. PMID- 21014122 TI - [Restorative plastic operations for concealing skin defects following lesions of the soft tissues]. PMID- 21014123 TI - [Plastics of periaural salivary fistulae with transposed scraps]. PMID- 21014125 TI - [Reflex contractures in surgical practice]. PMID- 21014124 TI - [Novocaine block of the nervus vagus in shock following injuries to the limbs]. PMID- 21014126 TI - [Ileus under disturbed nourishment]. PMID- 21014127 TI - [Penetrating wounds of the stomach]. PMID- 21014128 TI - [Orthopedical appliances in traumatic damages of the peripheral nervous system of the upper extremities]. PMID- 21014129 TI - [On closed fractures of the foot caused by a mine explosion]. PMID- 21014130 TI - [Osteoplastic amputations and reamputations]. PMID- 21014131 TI - [Concerning amputation in the middle third of the shank with osteomuscular aponeurotic scrap on the pedicle]. PMID- 21014132 TI - [Plastics with the tubulous scrap in amputations of the extremities]. PMID- 21014133 TI - Leiomyosarcoma of the stomach; its roentgenologic and gastroscopic diagnosis and its possible relation to pernicious anemia. PMID- 21014134 TI - Composite free grafts of skin and cartilage from the ear. PMID- 21014135 TI - Subcutaneous heparin in the Pitkin menstruum for the treatment of experimental human frostbite. PMID- 21014136 TI - Military surgery, United States Army, European theater of operations, 1944-45. PMID- 21014137 TI - The origin, frequency, and significance of microscopic calculi in the kidney. PMID- 21014138 TI - Resection of the rectum with reconstruction of canal through the perineal approach. PMID- 21014139 TI - Studies on exophthalmos produced by thyrotropic hormone; a study of exophthalmos produced by various thyrotropic hormones and the influence of the testes on the exophthalmos. PMID- 21014140 TI - Massive islet cell tumor of the pancreas without hypoglycemia. PMID- 21014141 TI - The surgical repair of the deep branch of the radial nerve. PMID- 21014142 TI - The treatment of burns; report of 155 cases. PMID- 21014143 TI - Electrolytic absorption of bone due to the use of stainless steels of different composition for internal fixation. PMID- 21014144 TI - A study of the value of local sulfathiazole in operative wounds in the prophylaxis of infection. PMID- 21014145 TI - Vasoepididymal anastomosis by production of permanent fistula with use of stainless steel wire. PMID- 21014146 TI - The treatment of varicose veins. PMID- 21014147 TI - Adenocarcinoma, cylindroma type, of the parotid gland. PMID- 21014148 TI - A clinical study of early postoperative ambulation in gynecology. PMID- 21014149 TI - Ipsilateral spastic rectus abdominis in a purely thoracic wound. PMID- 21014151 TI - Mapping sensory nerve injuries. PMID- 21014150 TI - Reconditioning at an Army amputation and neuro surgical center. PMID- 21014152 TI - Exercises for the convalescent bed patient. PMID- 21014153 TI - The functional anatomy of the shoulder girdle. PMID- 21014154 TI - [Not Available]. PMID- 21014155 TI - [Not Available]. PMID- 21014156 TI - [Not Available]. PMID- 21014157 TI - [Not Available]. PMID- 21014158 TI - [Not Available]. PMID- 21014159 TI - [Not Available]. PMID- 21014160 TI - [Not Available]. PMID- 21014161 TI - [Not Available]. PMID- 21014162 TI - [Not Available]. PMID- 21014163 TI - [Not Available]. PMID- 21014164 TI - [Not Available]. PMID- 21014165 TI - [Not Available]. PMID- 21014166 TI - [Not Available]. PMID- 21014167 TI - [Not Available]. PMID- 21014168 TI - [Not Available]. PMID- 21014169 TI - [Not Available]. PMID- 21014170 TI - [Not Available]. PMID- 21014171 TI - [Not Available]. PMID- 21014172 TI - [Not Available]. PMID- 21014173 TI - [Not Available]. PMID- 21014174 TI - [Not Available]. PMID- 21014175 TI - [Not Available]. PMID- 21014176 TI - [Not Available]. PMID- 21014177 TI - Orgone biophysics, mechanistic science and atomic energy. PMID- 21014178 TI - Experimental demonstration of the physical orgone energy. PMID- 21014179 TI - The development of the authoritarian state apparatus from rational social interrelationships. PMID- 21014180 TI - Studying The Children's Place. PMID- 21014181 TI - The child and his struggle. PMID- 21014182 TI - My first experiences with the orgone accumulator. PMID- 21014183 TI - SOME practical problems of adolescent sex relationships. PMID- 21014184 TI - Studies in swine erysipelas. PMID- 21014186 TI - A critique on disinfectants. PMID- 21014185 TI - Experimental work with sulfa compounds in pulmonary and enteric infections in swine. PMID- 21014187 TI - Original veterinary faculty. PMID- 21014188 TI - The importance of blood types in hemotherapy of animals. PMID- 21014189 TI - Cesarean section in a monkey. PMID- 21014190 TI - Phemerol as treatment for ringworm in calves. PMID- 21014191 TI - An interesting case report on leukemia in a dog. PMID- 21014192 TI - [Not Available]. PMID- 21014193 TI - [Not Available]. PMID- 21014194 TI - [Not Available]. PMID- 21014195 TI - [Not Available]. PMID- 21014196 TI - [Not Available]. PMID- 21014198 TI - [Not Available]. PMID- 21014197 TI - [Not Available]. PMID- 21014199 TI - [Not Available]. PMID- 21014200 TI - [Not Available]. PMID- 21014201 TI - [Not Available]. PMID- 21014202 TI - Corynebacterium pyogenes infections of domestic animals. PMID- 21014203 TI - Spraying trials with D.D.T. and 666 against the sheep blowfly. PMID- 21014204 TI - A venereal disease of sheep. PMID- 21014205 TI - INTRAMAMMARY therapy of bovine mastitis. PMID- 21014206 TI - Rennet extract. PMID- 21014207 TI - Studies on bovine mastitis; penicillin therapy in streptococcic mastitis. PMID- 21014208 TI - Concentration of hog-cholera virus in the blood of artificially infected swine at different stages of the disease. PMID- 21014209 TI - A newly developed anesthetic for horses. PMID- 21014210 TI - Anomalous posterior vena cava of a dog. PMID- 21014212 TI - An embryonal mixed tumor in the lungs of a calf. PMID- 21014211 TI - Effects of stilbestrol on pyometra following retained fetal membranes. PMID- 21014213 TI - Gallstones in a dog. PMID- 21014214 TI - Use of DDT to control sarcoptic mange. PMID- 21014215 TI - Sulfamerazine as a prophylactic in pullorum disease in poults. PMID- 21014216 TI - Penicillin in piroplasmosis of dogs. PMID- 21014217 TI - Eyeworms in a German shepherd. PMID- 21014218 TI - OBSERVATION of dogs transmitting leptospirosis to their masters. PMID- 21014219 TI - STREPTOMYCIN. PMID- 21014220 TI - Report on the use of a new acid-ester preparation in certain dermatological conditions in animals. PMID- 21014221 TI - RECOMMENDED nutrient allowances for dairy cattle. PMID- 21014222 TI - Chronic molybdenum poisoning in cattle. PMID- 21014223 TI - Further tests on a fit-producing dog food. PMID- 21014224 TI - The biotic provinces of Mexico. PMID- 21014226 TI - Morphological characters of the auditory ossicles of recent Talpidae. PMID- 21014227 TI - The hindfoot musculature of some basic ungulates. PMID- 21014225 TI - Brief comparison of short-tailed shrew and reptile poisons. PMID- 21014228 TI - Reactions of a rhesus monkey to embalmed corpses. PMID- 21014229 TI - Relation between quinoid structure and bacteriostatic activity of tetramethyl diaminodi-phenylmethane derivatives. PMID- 21014230 TI - Variation in Penicillium notatum induced by the bombardment of spores with neutrons. PMID- 21014231 TI - A study of fluid thioglycollate medium for the sterility test. PMID- 21014232 TI - Lipid production by a soil yeast. PMID- 21014233 TI - Studies on cellulose fermentation; an anaerobic cellulose-decomposing actinomycete, Micromonospora propionici, n. sp. PMID- 21014234 TI - Penicillin; production of penicillin in surface cultures. PMID- 21014235 TI - Penicillin; the laboratory scale production of penicillin in submerged cultures by Penicillium notatum Westling (NRRL 832). PMID- 21014236 TI - The combined action of penicillin and sulfonamides in vitro; the nature of the reaction. PMID- 21014237 TI - Two paracolon cultures related antigenically to Shigella paradysenteriae. PMID- 21014238 TI - On the existence, morphology, nature, and functions of the cytoplasmic membrane in the bacterial cell. PMID- 21014239 TI - A new Salmonella type, Salmonella cubana. PMID- 21014240 TI - Bacterial penicillinase; production, nature, and significance. PMID- 21014241 TI - Studies on blood agar; an improved blood agar base. PMID- 21014242 TI - Use of antibiotic substances for freeing Trichomonas fetus from bacteria. PMID- 21014243 TI - Limiting values for antibody; antigen ratio in the combination of diphtheria toxin with split antitoxic pseudoglobulin. PMID- 21014244 TI - The water balance in Ixodes ricinus L. and certain other species of ticks. PMID- 21014245 TI - Tobacco rosette, a complex virus disease. PMID- 21014246 TI - The transmission of plant viruses by aphides. PMID- 21014247 TI - A record of the nematode parasites of fishes from the Porcupine Bank, Irish Atlantic Slope and Irish Sea. PMID- 21014248 TI - Notes on Trombicula deliensis Walch, 1923 (Acarina, Trombidiidae), with description of the adult. PMID- 21014249 TI - Larval and nymphal mites (Acarina; Trombiculidae) from Ceylon and the Maldive Islands. PMID- 21014250 TI - Nairobi sheep disease; the survival of the virus in the tick Rhipicephalus appendiculatus. PMID- 21014251 TI - Rhipicephalus neavei Warburton, 1912 as a vector of East Coast fever. PMID- 21014252 TI - Observations on a monocystid gregarine, Apolocystic elongata n. sp., in the seminal vesicles of Eisenia foetida (Sav.). PMID- 21014253 TI - The ecology of the sheep tick, Ixodes ricinus L.; distribution of the tick on hill pasture. PMID- 21014254 TI - The biology of Ornithodorus delancei acinus Whittick, 1938. PMID- 21014256 TI - Studies on Entamoeba histolytica; the relation of oxidation-reduction potentials to the growth, encystation and excystation of Entamoeba histolytica in culture. PMID- 21014255 TI - Experiments upon the feeding of Aedes aegypti through animal membranes with a view to applying this method to the chemotherapy of malaria. PMID- 21014257 TI - Chemical control of seed-borne fungi during germination testing of peas and sweet corn. PMID- 21014258 TI - The effect of ultraviolet radiation on the viability of fungus spores and on the development of decay in sweet cherries. PMID- 21014259 TI - Field strains of tobacco-mosaic virus. PMID- 21014260 TI - Leafhopper transmission of the virus causing Pierce's disease of grape and dwarf of alfalfa. PMID- 21014262 TI - Two legume viruses transmissible to tobacco. PMID- 21014261 TI - Electrophoretic studies with the plant viruses. PMID- 21014263 TI - The antigenicity of southern bean mosaic virus. PMID- 21014264 TI - [Not Available]. PMID- 21014265 TI - [Not Available]. PMID- 21014266 TI - [Not Available]. PMID- 21014267 TI - [Not Available]. PMID- 21014268 TI - [Not Available]. PMID- 21014269 TI - [Not Available]. PMID- 21014270 TI - [Not Available]. PMID- 21014271 TI - [Not Available]. PMID- 21014272 TI - [Not Available]. PMID- 21014274 TI - Observations on the giant amoeba, Amoeba carolinensis (Wilson, 1900). PMID- 21014273 TI - Studies on ciliates of the family Ancistrocomidae Chatton and Lwoff (order Holotricha, suborder Thigmotricha) Hypocomina tegularum sp. nov. and Crebricoma gen. nov. PMID- 21014275 TI - The elimination of chromosomes in the meiotic divisions of Brachystethus rubromaculatus Dallas. PMID- 21014276 TI - An investigation of cross striations and myosin filaments in muscle. PMID- 21014277 TI - Micrurgical studies on Chironomus salivary gland chromosomes. PMID- 21014278 TI - [Not Available]. PMID- 21014279 TI - [Not Available]. PMID- 21014280 TI - [Not Available]. PMID- 21014281 TI - Morphogenetic studies of the rabbit; evidence of regionally specific hereditary factors influencing the extent of the lumbar region. PMID- 21014282 TI - A study of adrenal cortical tissue in Rana pipiens with special reference to metamorphosis. PMID- 21014283 TI - A new type of spermiogenesis in iceryine cocoids; with linear alignment of chromosomes in the sperm. PMID- 21014284 TI - The effect of uterine environment on the skeleton of the mouse. PMID- 21014285 TI - The relationship of skeletal type and body size in an inbred strain of mice. PMID- 21014286 TI - The anatomy and histology of the alimentary tract of the bottomfeeder, Mulloides auriflamma (Forsk.). PMID- 21014287 TI - Cephalogenesis in relation to the integration center of the beetle Callosobruchus maculatus Fabr. PMID- 21014288 TI - Chemoreceptivity of Drosophila melanogaster. PMID- 21014289 TI - Experimental chemotherapy of typhus; anti-rickettsial action of p sulphonamidobenzamidine and related compounds. PMID- 21014290 TI - Photochemical laws and visual phenomena. PMID- 21014291 TI - Further experiments on insect competition. PMID- 21014292 TI - Reflex conduction in the giant fibres of the earthworm. PMID- 21014293 TI - The active and passive exchanges of inorganic ions through the surfaces of living cells and through living membranes generally. PMID- 21014294 TI - The transmission of beet mosaic and beet yellows viruses by aphides; a comparative study of a nonpersistent and a persistent virus having host plants and vectors in common. PMID- 21014295 TI - The biological activity of phenolic compounds; the effect of surface active substances upon the penetration of hexyl resorcinol into Ascaris lumbricoides var. suls. PMID- 21014296 TI - [Not Available]. PMID- 21014297 TI - [Not Available]. PMID- 21014298 TI - [Not Available]. PMID- 21014299 TI - [Not Available]. PMID- 21014300 TI - [Not Available]. PMID- 21014301 TI - [Not Available]. PMID- 21014302 TI - The biochemistry of benzpyrene; a survey, and new methods of analysis. PMID- 21014303 TI - The biochemistry of benzpyrene; the course of its metabolism and the chemical nature of the metabolites. PMID- 21014304 TI - Effects of massive doses of methylcholanthrene on epidermal carcinogenesis. PMID- 21014305 TI - Neutralization of inhibition of tumor growth. PMID- 21014306 TI - Intraperitoneal sarcomas produced in mice with mouse ascitic fluid. PMID- 21014307 TI - Melanosarcoma and rhabdomyoma in two pine snakes (Pituophis melanoleucus). PMID- 21014308 TI - Betel chewing among natives of the Southwest Pacific Islands; lack of carcinogenic action. PMID- 21014309 TI - Histologic changes in the central vegetative centers of the hypothalamus in carcinoma as an indication of vegetative functional disturbances. PMID- 21014310 TI - [Not Available]. PMID- 21014311 TI - [Not Available]. PMID- 21014313 TI - [Not Available]. PMID- 21014312 TI - [Not Available]. PMID- 21014314 TI - [Not Available]. PMID- 21014315 TI - [Not Available]. PMID- 21014316 TI - Pericarditis with effusion following infections of the upper respiratory tract. PMID- 21014317 TI - Hemiplegia following carotid sinus stimulation. PMID- 21014319 TI - The rate and control of the blood flow through the skin of the lower extremities. PMID- 21014318 TI - Transitory A-V block occurring during scarlet fever. PMID- 21014320 TI - Electrocardiographic changes in cases of infectious hepatitis. PMID- 21014321 TI - A method for the construction of the vectorcardiogram from the Einthoven electrocardiogram. PMID- 21014322 TI - Differences in blood pressure values determined by inflating and deflating the cuff of the sphygmomanometer. PMID- 21014323 TI - Metastatic carcinoma as a cause of constrictive pericarditis. PMID- 21014324 TI - The cure of subacute bacterial endarteritis by surgical ligation in a patient with patent ductus arteriosus complicated by the presence of multiple congenital cardiac defects. PMID- 21014326 TI - [Not Available]. PMID- 21014325 TI - Mumps myocarditis; review of literature and report of case. PMID- 21014327 TI - [Not Available]. PMID- 21014328 TI - [Not Available]. PMID- 21014329 TI - [Not Available]. PMID- 21014330 TI - [Not Available]. PMID- 21014331 TI - [Not Available]. PMID- 21014332 TI - [Not Available]. PMID- 21014334 TI - [Not Available]. PMID- 21014333 TI - [Not Available]. PMID- 21014335 TI - [Not Available]. PMID- 21014336 TI - [Not Available]. PMID- 21014337 TI - Penicillin in dental and oral surgery. PMID- 21014338 TI - The development of alkali within saliva and its relation to dental caries. PMID- 21014339 TI - Some evidence of a wartime reduction of the caries incidence in children. PMID- 21014340 TI - Notes on prosthetic procedures. PMID- 21014341 TI - Impacted third molars and their sequelae. PMID- 21014342 TI - The individual unit porcelain bridge. PMID- 21014343 TI - A study of body sensitivity to dental infection. PMID- 21014344 TI - Carotid pressure and the relief of headache. PMID- 21014345 TI - Corrective surgery of the jaws. PMID- 21014346 TI - A report on the treatment of rampant caries with parathyroid extract. PMID- 21014347 TI - Psychological preparation for anaesthesia. PMID- 21014348 TI - Protection of the dental pulp. PMID- 21014349 TI - Vincent's infection; its incidence, aetiolgy, diagnosis, and treatment. PMID- 21014350 TI - Cervico-facial orthopaedia. PMID- 21014351 TI - Chewing as a therapeutic measure. PMID- 21014352 TI - Dental needs, dental demands and dental costs. PMID- 21014353 TI - Proposals of the Council on Dental Health, the American Dental Association. PMID- 21014355 TI - [Not Available]. PMID- 21014354 TI - The health of the American people. PMID- 21014356 TI - [Not Available]. PMID- 21014357 TI - [Not Available]. PMID- 21014358 TI - [Not Available]. PMID- 21014359 TI - [Not Available]. PMID- 21014360 TI - [Not Available]. PMID- 21014361 TI - [Not Available]. PMID- 21014362 TI - [Not Available]. PMID- 21014363 TI - [Not Available]. PMID- 21014364 TI - [Not Available]. PMID- 21014365 TI - [Not Available]. PMID- 21014366 TI - [Not Available]. PMID- 21014367 TI - [Not Available]. PMID- 21014368 TI - [Not Available]. PMID- 21014369 TI - [Not Available]. PMID- 21014370 TI - [Not Available]. PMID- 21014371 TI - [Not Available]. PMID- 21014372 TI - [Not Available]. PMID- 21014374 TI - SCIENCE contributes streptomycin. PMID- 21014373 TI - [Not Available]. PMID- 21014375 TI - DESIGUARD: a new safety shield for vacuum desiccators. PMID- 21014376 TI - HIGHLY accurate viscometer for low viscosity liquids. PMID- 21014378 TI - NEW and much improved Fisher Titrimeter. PMID- 21014377 TI - NEW rapid low-chromium method. PMID- 21014379 TI - ELECTROPHOTOMETER applications greatly extended. PMID- 21014380 TI - Producing dehydrated meats by drum-cabinet, retort-cabinet, and other methods. PMID- 21014381 TI - Preliminary investigation on measurement of color in canned foods. PMID- 21014382 TI - Compressibility of dehydrated meat. PMID- 21014383 TI - Vitamin A retention in dried eggs as affected by compression and packaging in tin cans. PMID- 21014384 TI - An investigation of the characters of dried whole egg determining baking quality for cakes other than sponge cakes. PMID- 21014385 TI - Improvement in digestibility of navy-bean starch. PMID- 21014387 TI - Retention of ascorbic acid in strawberries during processing, frozen storage, and manufacture of velva fruit. PMID- 21014386 TI - Retention of carotene, thiamin, riboflavin, and niacin during large-scale food service of dehydrated carrots. PMID- 21014388 TI - Organoleptic tests pertaining to apples and pears. PMID- 21014389 TI - Bataan and its aftermath. PMID- 21014390 TI - Food service problems in an Army hospital, ETO. PMID- 21014391 TI - Diet in infectious hepatitis. PMID- 21014392 TI - A nutritional review of large-scale feeding operations (U.S. Army). PMID- 21014393 TI - Messing aboard a large carrier and a modern battleship. PMID- 21014394 TI - Dietitians and the Veterans Administration. PMID- 21014395 TI - Objectives for teaching diet therapy in college courses. PMID- 21014396 TI - Child care centers contribute to America's future. PMID- 21014397 TI - The effect of pituitary adrenotrophic hormone on the cholesterol and ascorbic acid content of the adrenal of the rat and the guinea pig. PMID- 21014398 TI - The influence of diethylstilbestrol on alloxan diabetes paired feeding experiments. PMID- 21014399 TI - Metabolism of the steroid hormones; the isolation of an androgen from human urine containing an 11-oxygen substitution in the steroid ring. PMID- 21014400 TI - The effect of diet on the growth and survival of adrenalectomized rats treated with desoxycorticosterone acetate pellets. PMID- 21014401 TI - The influence of adrenalectomy on the utilization of acetone bodies. PMID- 21014402 TI - The role of the corpora allata in the development of Leucophaea (Orthoptera). PMID- 21014403 TI - The relationship between corpora allata and reproductive organs in adult Leucophaea maderae (Orthoptera). PMID- 21014404 TI - Methods for concentration of relaxin from blood serum and urine. PMID- 21014405 TI - A note on the mode of thiouracil action. PMID- 21014406 TI - Thiouracil treatment of thyrotoxicosis; the results of prolonged treatment. PMID- 21014407 TI - Thiouracil treatment of thyrotoxicosis; toxic reactions. PMID- 21014408 TI - Urinary 17-ketosteroids in metabolism; partition of gonadal and adrenocortical hormonal derivatives of normal, endocrine and cancerous patients. PMID- 21014409 TI - Degenerative changes in cerebral arteries following administration of desoxycorticosterone acetate. PMID- 21014410 TI - Methyl testosterone and surgical castration in the treatment of carcinoma of the breast. PMID- 21014411 TI - The effect of the administration of estrogens upon the production of cervical mucus in castrated women. PMID- 21014412 TI - [Not Available]. PMID- 21014413 TI - [Not Available]. PMID- 21014414 TI - [Not Available]. PMID- 21014415 TI - Causes of sterility in young married women. PMID- 21014417 TI - GOOD and bad habits. PMID- 21014416 TI - Social and economic problems of child-bearing; a proposed inquiry. PMID- 21014418 TI - [Not Available]. PMID- 21014419 TI - [Not Available]. PMID- 21014420 TI - [Not Available]. PMID- 21014421 TI - [Not Available]. PMID- 21014422 TI - [Not Available]. PMID- 21014423 TI - [Not Available]. PMID- 21014424 TI - [Not Available]. PMID- 21014425 TI - [Not Available]. PMID- 21014426 TI - [Not Available]. PMID- 21014427 TI - [Not Available]. PMID- 21014428 TI - [Not Available]. PMID- 21014429 TI - [Not Available]. PMID- 21014430 TI - [Not Available]. PMID- 21014431 TI - [Not Available]. PMID- 21014432 TI - [Not Available]. PMID- 21014433 TI - [Not Available]. PMID- 21014434 TI - [Not Available]. PMID- 21014435 TI - [Not Available]. PMID- 21014436 TI - [Not Available]. PMID- 21014437 TI - [Not Available]. PMID- 21014438 TI - [Not Available]. PMID- 21014439 TI - [Not Available]. PMID- 21014440 TI - [Not Available]. PMID- 21014441 TI - [Not Available]. PMID- 21014442 TI - [Not Available]. PMID- 21014443 TI - [Not Available]. PMID- 21014444 TI - [Not Available]. PMID- 21014445 TI - The roentgen diagnosis of disease of the gastro-intestinal tract; some facts and fallacies. PMID- 21014446 TI - The chemical and electrical origin of nervous energy. PMID- 21014447 TI - The abuse of vaso constrictors in acute nasal inflammation. PMID- 21014448 TI - Influence of ephedrine sulfate on blood pressure in hypertensive rats. PMID- 21014449 TI - Introduction to an advanced physiological concept in orthopodics; evaluation and modification of Wolff's law. PMID- 21014450 TI - The rationale of athlete's foot. PMID- 21014451 TI - The use of histamine ointment in recurrent bursitis of the feet. PMID- 21014453 TI - [Not Available]. PMID- 21014452 TI - Chinese medicine; ancient and modern. PMID- 21014454 TI - Can the voluntary hospital be fitted into the municipal hospital plan? PMID- 21014455 TI - MODERN small hospital serves rural community. PMID- 21014456 TI - Tuberculosis case-finding project. PMID- 21014457 TI - Care of the chronically ill. PMID- 21014458 TI - Trends in nursing in Illinois State Nurses Association. PMID- 21014459 TI - American hospitals; some impressions and reflections. PMID- 21014461 TI - Hospital services in Australia; some impressions gained during a recent tour. PMID- 21014460 TI - The last resource; is the mental hospital in its present form inevitable? PMID- 21014462 TI - Heating in hospitals. PMID- 21014463 TI - Consents to operations and other surgical procedures. PMID- 21014464 TI - An inquiry into the 1946 outlook for construction funds. PMID- 21014465 TI - HOSPITAL facilities in relation to community wealth. PMID- 21014466 TI - What to consider in seeking a commercial loan. PMID- 21014467 TI - SUCCESSFUL midyear conference emphasized administrative problems. PMID- 21014468 TI - Even the crippled can work efficiently. PMID- 21014469 TI - Fighting poliomelitis calls for joint effort. PMID- 21014470 TI - The minimum equipment required for a useful hospital pharmacy. PMID- 21014471 TI - A method for establishing inclusive rates. PMID- 21014472 TI - Inter-American cooperation builds health program in Paraguay. PMID- 21014473 TI - Common sense, not magic, is key to personnel policy. PMID- 21014474 TI - HOW the Michigan plan operates. PMID- 21014475 TI - Not room rate, but daily service charges. PMID- 21014476 TI - Ethics, laws, and medical records. PMID- 21014477 TI - Something new added at St. Elizabeth's Hospital, Boston, Massachusetts. PMID- 21014478 TI - The obstetrical department in a general hospital. PMID- 21014479 TI - The Sisters of the Poor of St. Francis, 1845-1945. PMID- 21014480 TI - The development and extension of pediatric service in postwar planning. PMID- 21014481 TI - The social structure of the Army. PMID- 21014482 TI - INFORMAL social organization in the Army. PMID- 21014483 TI - Characteristics of military society. PMID- 21014484 TI - Aggressive and erotic tendencies in Army life. PMID- 21014485 TI - Aggressiveness and military training. PMID- 21014486 TI - Adjustment to military life. PMID- 21014487 TI - Group psychotherapy of military offenders. PMID- 21014488 TI - The combat neuroses. PMID- 21014489 TI - The study of the delinquent in the Army. PMID- 21014490 TI - Research on veterans' adjustment. PMID- 21014491 TI - Management of civilian disaster burns. PMID- 21014492 TI - Esprit de corps among catastrophe victims. PMID- 21014494 TI - Bacteriostatics employed and medical problems. PMID- 21014493 TI - The laboratory in the burn catastrophe. PMID- 21014495 TI - Neuroses of peace and of war. PMID- 21014496 TI - Lumbar herniations of intervertebral disks; value of surgical removal for Naval personnel. PMID- 21014497 TI - The thymol-barbital test in experimental carbon tetrachloride poisoning. PMID- 21014498 TI - Actual causes of certain occupational dermatoses; a further study of five hundred and thirty-two cases with special reference to dermatitis caused by certain petroleum solvents. PMID- 21014499 TI - [Not Available]. PMID- 21014500 TI - [Not Available]. PMID- 21014502 TI - [Not Available]. PMID- 21014501 TI - [Not Available]. PMID- 21014503 TI - [Not Available]. PMID- 21014504 TI - [Not Available]. PMID- 21014505 TI - [Not Available]. PMID- 21014506 TI - [Not Available]. PMID- 21014507 TI - [Not Available]. PMID- 21014508 TI - [Not Available]. PMID- 21014510 TI - Thrombangiitis obliterans, a disease of the entire vascular system. PMID- 21014509 TI - Trial with penicillin in certain cases of thrombangiitis obliterans (Buerger's disease). PMID- 21014511 TI - Amoebiasis and rheumatism. PMID- 21014512 TI - A case of thrombosis of the cavernous sinus. PMID- 21014513 TI - [Not Available]. PMID- 21014514 TI - [Not Available]. PMID- 21014515 TI - [Not Available]. PMID- 21014516 TI - [Not Available]. PMID- 21014517 TI - [Not Available]. PMID- 21014518 TI - [Not Available]. PMID- 21014519 TI - [Not Available]. PMID- 21014520 TI - [Not Available]. PMID- 21014521 TI - [Not Available]. PMID- 21014522 TI - [Not Available]. PMID- 21014523 TI - [Not Available]. PMID- 21014524 TI - [Not Available]. PMID- 21014525 TI - [Not Available]. PMID- 21014526 TI - [Not Available]. PMID- 21014527 TI - [Not Available]. PMID- 21014528 TI - [Not Available]. PMID- 21014529 TI - [Not Available]. PMID- 21014530 TI - Investigations on Mucuna seeds; biological value of proteins of the seeds of Mucuna utilis, Wall. PMID- 21014531 TI - Biological value of proteins of palmyra fruits (Borassus flabellifer, Linn). PMID- 21014532 TI - On plant phosphatases; leaf phosphatases; distribution and general properties. PMID- 21014533 TI - Observations on ascorbic acid; state of ascorbic acid in plant tissues. PMID- 21014534 TI - Observations on ascorbic acid; state of ascorbic acid in urine. PMID- 21014535 TI - Observations on ascorbic acid; effect of methods of preservation on ascorbic acid content of fruits. PMID- 21014536 TI - [Not Available]. PMID- 21014537 TI - [Not Available]. PMID- 21014538 TI - [Not Available]. PMID- 21014539 TI - Meningococcemia with gangrene; report of the recovery of a case in which meningococci were found in direct blood smears. PMID- 21014540 TI - Disseminated lupus erythematosus. PMID- 21014541 TI - The frog test in the diagnosis of early pregnancy. PMID- 21014542 TI - The Blue Cross, the hospital, the physician. PMID- 21014543 TI - USE of sulfonamides in burn therapy. PMID- 21014544 TI - The role of trauma in acute coronary thrombosis; a clinical study of 200 cases. PMID- 21014545 TI - [Not Available]. PMID- 21014546 TI - [Not Available]. PMID- 21014547 TI - [Not Available]. PMID- 21014548 TI - [Not Available]. PMID- 21014550 TI - [Not Available]. PMID- 21014549 TI - [Not Available]. PMID- 21014551 TI - [Not Available]. PMID- 21014552 TI - [Not Available]. PMID- 21014553 TI - A review of scabies since 1939. PMID- 21014554 TI - Recent work on the louse (Pediculus humanus L.). PMID- 21014555 TI - Recent work on mosquito control. PMID- 21014556 TI - Insect repellents. PMID- 21014557 TI - Modern developments in fly control. PMID- 21014558 TI - Scrub-typhus: a disease of man transmitted by mites. PMID- 21014559 TI - The design and use of sprayers for insect control. PMID- 21014560 TI - Risks to man and animals from the use of 2,2-bis (p-chlorphenyl), l,l,l, trichlorethane (DDT) with a note on the toxicology of y-benzene hexachloride (666, gammexane). PMID- 21014561 TI - BICENTENARY of Heberden's Antitheriaka. PMID- 21014562 TI - Primary atypical pneumonia. PMID- 21014563 TI - Fractured patella; an analysis of 54 cases treated by excision. PMID- 21014564 TI - Vitamin C content of home-cooked vegetables. PMID- 21014565 TI - Neurological complications following prefrontal leucotomy. PMID- 21014566 TI - Primary benign tertian malaria among British troops in Normandy. PMID- 21014567 TI - A method of closed anastomosis. PMID- 21014568 TI - Obstructed transmesenteric hernia. PMID- 21014569 TI - A general surgeon at sea; a review of 700 cases treated in the Downs. PMID- 21014570 TI - Chronic cholecystitis. PMID- 21014571 TI - D.D.T. poisoning. PMID- 21014572 TI - Expulsion of pathogenic organisms from the respiratory tract. PMID- 21014573 TI - Plasma viscosity: a clinical test. PMID- 21014574 TI - Non-absorption of mepacrine: description of a case. PMID- 21014575 TI - The cephalin flocculation test in malaria. PMID- 21014576 TI - Some paediatric problems presented at Belsen Camp. PMID- 21014577 TI - Spontaneous rupture of the liver complicating pregnancy. PMID- 21014578 TI - Unusual sequel of a large overdose of insulin. PMID- 21014579 TI - STREPTOMYCIN in tuberculosis. PMID- 21014580 TI - Notes on the psychology of prisoners of war. PMID- 21014581 TI - Homosexuality. PMID- 21014582 TI - Eye conditions in industrial medicine. PMID- 21014583 TI - Control of welding fumes. PMID- 21014584 TI - The control of lead hazard in industry. PMID- 21014585 TI - Some aspects of cancer research. PMID- 21014586 TI - Thrombophlebitis of the dorsal vein of the penis; with case report. PMID- 21014587 TI - Cardiac aneurysm with rupture. PMID- 21014588 TI - Adenocarcinoma of the ethmoid sinus. PMID- 21014589 TI - Diverticulum of the female urethra; review of literature with case report. PMID- 21014590 TI - The effect of penicillin in experimental intestinal obstruction; preliminary report on closed loop studies. PMID- 21014591 TI - The experimental production of anaphylactic pulmonary lesions with the basic characteristics of rheumatic pneumonitis. PMID- 21014592 TI - The relation of the degree of sensitivity to tuberculin to the persistence of sensitivity and to prognosis in young children. PMID- 21014593 TI - Studies on acute Schistosomiasis japonica in the Philippine Islands; a clinical study of 337 cases with a preliminary report on the results of treatment with fuadin in 110 cases. PMID- 21014594 TI - The clinical applications of electroencephalography. PMID- 21014596 TI - [Acute yellow atrophy of liver]. PMID- 21014595 TI - Streptomycin quality and standards. PMID- 21014597 TI - The application of nuclear physics to biology and medicine. PMID- 21014598 TI - On the mechanism of bacterial invasion. PMID- 21014599 TI - MENINGIOMA of the cervical spinal dura with post-operative uremia and renal insufficiency. PMID- 21014600 TI - Newer aspects of surgical treatment of cavities in pulmonary tuberculosis. PMID- 21014601 TI - Differential diagnosis of the chief vascular diseases causing gangrene of the extremities. PMID- 21014602 TI - Removal of a benign tumor from the face. PMID- 21014603 TI - Tuberculosis and mycotic infections of the lungs: synergistic relations. PMID- 21014604 TI - DIAGNOSIS of minimal tuberculosis. PMID- 21014605 TI - Cystic disease of the lungs. PMID- 21014606 TI - MALARIA control in Burma. PMID- 21014607 TI - The problem of diagnosis in mumps; a seminar. PMID- 21014608 TI - [Not Available]. PMID- 21014609 TI - [Not Available]. PMID- 21014610 TI - [Not Available]. PMID- 21014611 TI - [Not Available]. PMID- 21014612 TI - [Not Available]. PMID- 21014613 TI - [Not Available]. PMID- 21014615 TI - [Not Available]. PMID- 21014614 TI - [Not Available]. PMID- 21014616 TI - The present status of radiation therapy of cancer. PMID- 21014617 TI - Occupational dermatitis; report of a survey of 368 cases. PMID- 21014618 TI - NEW HAVEN Industrial Medical Service; a summary of 3 1/2 years of experience. PMID- 21014619 TI - Acute fatal methyl salicylate toxicity; report of a case. PMID- 21014620 TI - Notes on the history of orthopedic surgery in Connecticut. PMID- 21014621 TI - [Not Available]. PMID- 21014622 TI - [Not Available]. PMID- 21014623 TI - [Not Available]. PMID- 21014624 TI - [Not Available]. PMID- 21014625 TI - [Not Available]. PMID- 21014626 TI - [Not Available]. PMID- 21014627 TI - [Not Available]. PMID- 21014628 TI - [Not Available]. PMID- 21014629 TI - [Not Available]. PMID- 21014630 TI - Cancer of the rectum. PMID- 21014631 TI - Orpington, 1939-1945. PMID- 21014632 TI - Tracheotomy in leprosy. PMID- 21014633 TI - Pellagra; a report of two cases. PMID- 21014634 TI - Cold agglutinins in virus type pneumonia. PMID- 21014635 TI - Penicillin therapy in purulent maxillary sinusitis. PMID- 21014637 TI - [Not Available]. PMID- 21014638 TI - [Not Available]. PMID- 21014636 TI - Reemployment of neuropsychiatric dischargees. PMID- 21014639 TI - [Not Available]. PMID- 21014640 TI - [Not Available]. PMID- 21014641 TI - [Not Available]. PMID- 21014642 TI - [Not Available]. PMID- 21014643 TI - [Not Available]. PMID- 21014644 TI - [Not Available]. PMID- 21014645 TI - [Not Available]. PMID- 21014646 TI - [Not Available]. PMID- 21014647 TI - [Not Available]. PMID- 21014648 TI - [Not Available]. PMID- 21014649 TI - The trend of pathology in Eire. PMID- 21014650 TI - Acute head injuries. PMID- 21014651 TI - Blood levels of calcium, inorganic phosphorus and alkaline phosphatase in relation to social position and tuberculous infection. PMID- 21014652 TI - A tuberculosis contact survey. PMID- 21014653 TI - Potassium and the cell. PMID- 21014654 TI - A plea for early diagnosis of cancer of the oesophagus. PMID- 21014655 TI - The need for a child guidance service. PMID- 21014656 TI - A case of single pregnancy in a uterus pseudodidelphys. PMID- 21014657 TI - Discovery of new drugs for specific therapy. PMID- 21014658 TI - Malaria toxin and action of quinine in clinical malaria. PMID- 21014659 TI - Idiopathic pulmo-eosinophilaemia. PMID- 21014660 TI - Malaria nephritis with an illustrative case report. PMID- 21014661 TI - Climate and tuberculosis. PMID- 21014662 TI - On the significance of using decomplementised serum in blood-matching. PMID- 21014663 TI - Health services of the Soviet Union. PMID- 21014665 TI - POSTMORTEM examination. PMID- 21014664 TI - Progress of surgery in the province of Madras. PMID- 21014666 TI - Chinese native ophthalmology. PMID- 21014667 TI - Tropical diseases in returning military personnel. PMID- 21014668 TI - Sudden death during the clinically convalescent stage of anterior poliomyelitis. PMID- 21014669 TI - Subacute bacterial endocarditis treated with penicillin; case report. PMID- 21014670 TI - USE of physostigmine in arthritis. PMID- 21014671 TI - The moral foundations of a national medical service. PMID- 21014672 TI - Progress in neurology. PMID- 21014673 TI - The control of stature. PMID- 21014674 TI - Chronic hyperthyroidism. PMID- 21014675 TI - Pulsating hematoma. PMID- 21014676 TI - Lichen planus treated with calcium lactate. PMID- 21014677 TI - Clinical manifestations of rheumatic fever; determination of rheumatic activity. PMID- 21014678 TI - Rheumatic heart disease; the use of x-ray in diagnosis. PMID- 21014679 TI - Chorea. PMID- 21014680 TI - The influence of light upon the pituitary gland and its functions. PMID- 21014681 TI - Chronic non-specific prostatitis and gastrointestinal complaints. PMID- 21014682 TI - Thrombosis of the basilic, axillary and subclavian veins, of undetermined origin. PMID- 21014683 TI - The treatment of the diarrheas. PMID- 21014684 TI - Two cases of ozena cured by Pickrell solution. PMID- 21014685 TI - Cheese poisoning in Syria and the Lebanon. PMID- 21014686 TI - Investigation of the gallbladder. PMID- 21014687 TI - Some facts about the incidence of diseases in Iraq. PMID- 21014688 TI - Odontalgia in normal teeth. PMID- 21014689 TI - The radical mastoid operation through the external auditory meatus. PMID- 21014690 TI - A case of severe lipoemia and xanthoma. PMID- 21014691 TI - Treatment of large pyogenic lung abscesses with penicillin and artificial pneumothorax. PMID- 21014692 TI - [Not Available]. PMID- 21014693 TI - [Not Available]. PMID- 21014694 TI - [Not Available]. PMID- 21014695 TI - Ancient apothecaries and modern biochemists. PMID- 21014696 TI - Treatment of macrocytic anaemia with folic acid. PMID- 21014697 TI - Pheumococcal meningitis after head injury, treated with intrathecal penicillin. PMID- 21014698 TI - Endemic fluorosis in Kweichow, China. PMID- 21014699 TI - Unsuspected genital tuberculosis as a main cause of tubal occlusion. PMID- 21014700 TI - Let's go to the pictures; the film in medical education. PMID- 21014702 TI - Vibratory fremitus; the use of the tuning fork in auscultation as a sign in the detection of chest diseases. PMID- 21014701 TI - Present status of research on the Rh factor. PMID- 21014703 TI - The treatment of gonorrhea by a single injection of a penicillin-oil-beeswax mixture. PMID- 21014704 TI - Ringworm of the scalp. PMID- 21014705 TI - [Not Available]. PMID- 21014707 TI - [Not Available]. PMID- 21014708 TI - Murine typhus fever. PMID- 21014706 TI - [Not Available]. PMID- 21014709 TI - An investigation of the effects of recurrent malaria; an organic and psychological analysis of 50 soldiers. PMID- 21014710 TI - Experimental epidemiology. PMID- 21014711 TI - Medical aspects of Red Cross in the second World war. PMID- 21014712 TI - Acquired resistance of staphylococci to the action of penicillin. PMID- 21014713 TI - Pleuropneumonia-like organisms in cases of non-gonococcal urethritis in man and in normal female genitalia. PMID- 21014715 TI - Lipomata of the uterus, with report of a case. PMID- 21014714 TI - Early results in a short series of cases of gunshot wounds of the abdomen. PMID- 21014716 TI - The treatment of inguinal hernia. PMID- 21014717 TI - Rupture of the liver in the newborn; recovery after blood transfusion and laparotomy. PMID- 21014718 TI - Report of a fatal case of blast injury of the spinal cord. PMID- 21014719 TI - Uterine pains in labour. PMID- 21014720 TI - Analgesia in labour. PMID- 21014721 TI - Anaesthesia in childbirth. PMID- 21014722 TI - Management of the third stage of labour. PMID- 21014723 TI - Episiotomy and perineal repair. PMID- 21014724 TI - Points in aseptic technique. PMID- 21014726 TI - Reflections on occupational influences and requirements in the tuberculous. PMID- 21014725 TI - The treatment of a premature baby; with special reference to the baby born and treated in its own home. PMID- 21014727 TI - Accounting records for the medical profession (with hints on tax saving). PMID- 21014728 TI - Treatment of pulmonary tuberculosis in the young adult. PMID- 21014729 TI - On rare diseases and syndromes, with some examples. PMID- 21014730 TI - The Volims-Griffiths plan. PMID- 21014732 TI - Laboratory investigations on the viruses of epidemic influenza. PMID- 21014731 TI - The pandemic of influenza of 1918-1919. PMID- 21014733 TI - Treatment of influenza. PMID- 21014734 TI - The sulphonamides: present place in therapeutics. PMID- 21014735 TI - The modern treatment of gonorrhoea. PMID- 21014736 TI - The science of therapy. PMID- 21014737 TI - A chemical test for the presence of cancer; its early detection and destruction by the selective action of bromo- and chloro-butyrates. PMID- 21014738 TI - A case of staphylococcal bacterial endocarditis successfully treated with an intermittent course of penicillin. PMID- 21014739 TI - The importance and significance of a thorough clinical examination in surgical diagnosis. PMID- 21014740 TI - Otosclerosis. PMID- 21014741 TI - Tuberculosis; the problem of its cure and prevention. PMID- 21014742 TI - The management of the septic hand. PMID- 21014743 TI - Tuberculosis; the problem of its cure and prevention; is the profession to blame for its failure? PMID- 21014744 TI - Anaesthesia by injection. PMID- 21014745 TI - [Not Available]. PMID- 21014746 TI - [Not Available]. PMID- 21014747 TI - [Not Available]. PMID- 21014748 TI - [Not Available]. PMID- 21014749 TI - [Not Available]. PMID- 21014750 TI - [Not Available]. PMID- 21014751 TI - [Not Available]. PMID- 21014752 TI - [Not Available]. PMID- 21014753 TI - [Not Available]. PMID- 21014754 TI - [Not Available]. PMID- 21014755 TI - [Not Available]. PMID- 21014756 TI - [Not Available]. PMID- 21014758 TI - [Not Available]. PMID- 21014757 TI - [Not Available]. PMID- 21014759 TI - [Not Available]. PMID- 21014760 TI - [Not Available]. PMID- 21014761 TI - [Not Available]. PMID- 21014762 TI - X-ray and radium management of cancer of the cervix. PMID- 21014763 TI - Management of coronary occlusion. PMID- 21014764 TI - Benign gastric tumors; report of three cases. PMID- 21014765 TI - The deafened school child in Nebraska. PMID- 21014766 TI - Bronchogenic carcinoma of the lung; report of a case. PMID- 21014767 TI - The response of the physician to regimentation. PMID- 21014768 TI - Nebraska surgical plan; its accomplishments and its aims. PMID- 21014769 TI - Silent and masquerading intrathoracic lesions; the importance of proper identification of lesions discovered during x-ray survey. PMID- 21014770 TI - Homologous serum jaundice following the administration of commercial pooled plasma; a report of eight cases including one fatality. PMID- 21014771 TI - Typhoid-bacillus infection of a surgical wound; treatment with a urethane sulfanilamide mixture; report of a case. PMID- 21014772 TI - Medical practice and its future. PMID- 21014773 TI - Neurinoma of stomach. PMID- 21014774 TI - Dissecting aneurysm of aorta, with rupture into pericardium. PMID- 21014775 TI - [Not Available]. PMID- 21014776 TI - [Not Available]. PMID- 21014777 TI - [Not Available]. PMID- 21014778 TI - [Not Available]. PMID- 21014780 TI - [Not Available]. PMID- 21014779 TI - [Not Available]. PMID- 21014781 TI - [Pneumonia]. PMID- 21014782 TI - The Rh factor in pregnancy and isohemolytic disease. PMID- 21014783 TI - Comments on war neuroses. PMID- 21014784 TI - Colloidal sulfur; some pharmacodynamic considerations and their therapeutic application in seborrheic dermatoses. PMID- 21014785 TI - Objectors to electric shock treatment are refractory to its therapy. PMID- 21014786 TI - The management of varicose ulcers. PMID- 21014787 TI - Duodenal obstruction caused by chronic pyelonephritis and hydronephrosis. PMID- 21014788 TI - Occlusion of the aortic bifurcation; with theoretic considerations regarding the production of signs and symptoms in two cases. PMID- 21014789 TI - ARMY Institute of Pathology; Army Medical Museum. PMID- 21014790 TI - [Not Available]. PMID- 21014791 TI - [Not Available]. PMID- 21014792 TI - [Not Available]. PMID- 21014793 TI - [Not Available]. PMID- 21014794 TI - [Not Available]. PMID- 21014795 TI - [Not Available]. PMID- 21014796 TI - [Not Available]. PMID- 21014797 TI - [Not Available]. PMID- 21014798 TI - [Not Available]. PMID- 21014800 TI - [Not Available]. PMID- 21014799 TI - [Not Available]. PMID- 21014801 TI - [Not Available]. PMID- 21014802 TI - [Not Available]. PMID- 21014803 TI - [Not Available]. PMID- 21014804 TI - [Not Available]. PMID- 21014805 TI - [Not Available]. PMID- 21014807 TI - [Not Available]. PMID- 21014806 TI - [Not Available]. PMID- 21014808 TI - [Not Available]. PMID- 21014809 TI - [Not Available]. PMID- 21014810 TI - [Not Available]. PMID- 21014811 TI - [Not Available]. PMID- 21014812 TI - [Not Available]. PMID- 21014813 TI - Antiseptics, old and new. PMID- 21014814 TI - An improved ring pinch clamp. PMID- 21014816 TI - Ozena; bacteriologic and pathologic studies. PMID- 21014815 TI - The historic development of knowledge relating to the coronary circulation and its diseases; the nineteenth century. PMID- 21014817 TI - The excretion and concentration of penicillin and streptomycin in the abnormal human biliary tract; preliminary report. PMID- 21014818 TI - [Not Available]. PMID- 21014819 TI - [Not Available]. PMID- 21014820 TI - [Not Available]. PMID- 21014821 TI - [Not Available]. PMID- 21014822 TI - [Not Available]. PMID- 21014823 TI - [Not Available]. PMID- 21014824 TI - [Not Available]. PMID- 21014825 TI - [Not Available]. PMID- 21014826 TI - [Not Available]. PMID- 21014828 TI - [Not Available]. PMID- 21014827 TI - [Not Available]. PMID- 21014829 TI - [Not Available]. PMID- 21014830 TI - [Not Available]. PMID- 21014831 TI - [Not Available]. PMID- 21014832 TI - [Not Available]. PMID- 21014833 TI - [Not Available]. PMID- 21014834 TI - [Not Available]. PMID- 21014835 TI - [Not Available]. PMID- 21014836 TI - [Not Available]. PMID- 21014837 TI - [Not Available]. PMID- 21014838 TI - [Not Available]. PMID- 21014839 TI - [Not Available]. PMID- 21014840 TI - [Not Available]. PMID- 21014841 TI - [Not Available]. PMID- 21014842 TI - [Not Available]. PMID- 21014843 TI - [Not Available]. PMID- 21014845 TI - [Not Available]. PMID- 21014844 TI - [Not Available]. PMID- 21014846 TI - [Not Available]. PMID- 21014847 TI - [Not Available]. PMID- 21014848 TI - [Not Available]. PMID- 21014849 TI - [Not Available]. PMID- 21014850 TI - [Not Available]. PMID- 21014851 TI - [Not Available]. PMID- 21014852 TI - [Not Available]. PMID- 21014853 TI - [Not Available]. PMID- 21014854 TI - [Not Available]. PMID- 21014855 TI - [Not Available]. PMID- 21014856 TI - [Not Available]. PMID- 21014857 TI - [Not Available]. PMID- 21014858 TI - [Not Available]. PMID- 21014859 TI - [Not Available]. PMID- 21014860 TI - [Not Available]. PMID- 21014861 TI - [Not Available]. PMID- 21014863 TI - [Not Available]. PMID- 21014862 TI - [Not Available]. PMID- 21014864 TI - [Not Available]. PMID- 21014865 TI - [Not Available]. PMID- 21014866 TI - [Not Available]. PMID- 21014867 TI - [Not Available]. PMID- 21014868 TI - [Not Available]. PMID- 21014869 TI - [Not Available]. PMID- 21014870 TI - [Not Available]. PMID- 21014871 TI - [Not Available]. PMID- 21014872 TI - [Not Available]. PMID- 21014873 TI - [Not Available]. PMID- 21014874 TI - [Not Available]. PMID- 21014875 TI - [Not Available]. PMID- 21014876 TI - [Not Available]. PMID- 21014877 TI - [Not Available]. PMID- 21014878 TI - [Not Available]. PMID- 21014879 TI - [Not Available]. PMID- 21014880 TI - [Not Available]. PMID- 21014881 TI - [Not Available]. PMID- 21014882 TI - [Not Available]. PMID- 21014883 TI - [Not Available]. PMID- 21014884 TI - [Not Available]. PMID- 21014885 TI - [Not Available]. PMID- 21014886 TI - [Not Available]. PMID- 21014887 TI - [Not Available]. PMID- 21014888 TI - [Not Available]. PMID- 21014889 TI - [Not Available]. PMID- 21014890 TI - St. Bartholomew's Hospital seventy years ago. PMID- 21014891 TI - Vaccination in the tropics. PMID- 21014892 TI - [Not Available]. PMID- 21014893 TI - [Not Available]. PMID- 21014894 TI - [Not Available]. PMID- 21014895 TI - [Not Available]. PMID- 21014896 TI - [Not Available]. PMID- 21014897 TI - [Not Available]. PMID- 21014898 TI - [Not Available]. PMID- 21014899 TI - [Not Available]. PMID- 21014900 TI - [Not Available]. PMID- 21014901 TI - [Not Available]. PMID- 21014902 TI - [Not Available]. PMID- 21014903 TI - [Not Available]. PMID- 21014904 TI - [Not Available]. PMID- 21014905 TI - [Not Available]. PMID- 21014906 TI - [Not Available]. PMID- 21014907 TI - [Not Available]. PMID- 21014908 TI - [Not Available]. PMID- 21014910 TI - [Not Available]. PMID- 21014909 TI - [Not Available]. PMID- 21014911 TI - [Not Available]. PMID- 21014912 TI - [Not Available]. PMID- 21014913 TI - [Not Available]. PMID- 21014914 TI - [Not Available]. PMID- 21014915 TI - [Not Available]. PMID- 21014916 TI - [Not Available]. PMID- 21014917 TI - [Not Available]. PMID- 21014918 TI - [Not Available]. PMID- 21014919 TI - [Not Available]. PMID- 21014920 TI - [Not Available]. PMID- 21014921 TI - [Not Available]. PMID- 21014922 TI - [Not Available]. PMID- 21014923 TI - [Not Available]. PMID- 21014924 TI - [Not Available]. PMID- 21014925 TI - [Not Available]. PMID- 21014926 TI - [Not Available]. PMID- 21014927 TI - [Not Available]. PMID- 21014928 TI - [Not Available]. PMID- 21014929 TI - [Not Available]. PMID- 21014930 TI - [Not Available]. PMID- 21014931 TI - [Not Available]. PMID- 21014932 TI - [Not Available]. PMID- 21014933 TI - [Not Available]. PMID- 21014934 TI - [Not Available]. PMID- 21014935 TI - [Not Available]. PMID- 21014936 TI - [Not Available]. PMID- 21014937 TI - [Not Available]. PMID- 21014939 TI - [Not Available]. PMID- 21014938 TI - [Not Available]. PMID- 21014940 TI - [Not Available]. PMID- 21014941 TI - [Not Available]. PMID- 21014942 TI - [Not Available]. PMID- 21014943 TI - Saddle block anesthesia with nupercaine for obstetrics. PMID- 21014944 TI - Mass venereal disease control in urban area. PMID- 21014945 TI - Infiltrating carcinoma of the urinary bladder; diagnosis and clinical evaluation of curability. PMID- 21014946 TI - The surgical approach to the lumbar ureter and kidney through the superior lumbar triangle. PMID- 21014947 TI - Physical rehabilitation of severely handicapped persons. PMID- 21014948 TI - Postabortal perforation of the uterus with foreign body in the abdomen. PMID- 21014949 TI - Amyotonia congenita (Oppenheim's disease). PMID- 21014950 TI - Penicillin in the treatment of syphilis; results and complications. PMID- 21014951 TI - Prediction of the requirements necessary for effective penicillin therapy. PMID- 21014952 TI - Management of dermatophytosis. PMID- 21014953 TI - Experiences in the phychotherapy of obsessive-schizophrenic personalities. PMID- 21014954 TI - Does Rh-factor incompatibility explain all cases of hemolytic anemia of the newborn? PMID- 21014955 TI - Some observations concerning the Salzer method of treatment of lye burns of the esophagus. PMID- 21014956 TI - Deficiency diseases in general practice. PMID- 21014957 TI - The substitution of thymine for folic acid in the treatment of macrocytic anemias in relapse. PMID- 21014958 TI - For early diagnosis of cancer of the stomach. PMID- 21014959 TI - It seems that somebody is still constipated. PMID- 21014960 TI - Treatment of heart failure. PMID- 21014961 TI - Starvation and its treatment with protein hydrolysate, Belsen, 1945. PMID- 21014962 TI - [Not Available]. PMID- 21014963 TI - [Not Available]. PMID- 21014964 TI - [Not Available]. PMID- 21014965 TI - [Not Available]. PMID- 21014966 TI - [Not Available]. PMID- 21014967 TI - [Not Available]. PMID- 21014968 TI - [Not Available]. PMID- 21014969 TI - [Not Available]. PMID- 21014970 TI - [Not Available]. PMID- 21014971 TI - [Not Available]. PMID- 21014972 TI - [Not Available]. PMID- 21014973 TI - [Not Available]. PMID- 21014975 TI - [Not Available]. PMID- 21014974 TI - [Not Available]. PMID- 21014976 TI - [Not Available]. PMID- 21014977 TI - [Not Available]. PMID- 21014978 TI - [Not Available]. PMID- 21014979 TI - [Not Available]. PMID- 21014980 TI - [Not Available]. PMID- 21014981 TI - [Not Available]. PMID- 21014982 TI - [Not Available]. PMID- 21014983 TI - [Not Available]. PMID- 21014984 TI - [Not Available]. PMID- 21014985 TI - [Not Available]. PMID- 21014986 TI - [Not Available]. PMID- 21014987 TI - [Not Available]. PMID- 21014988 TI - [Not Available]. PMID- 21014989 TI - [Not Available]. PMID- 21014991 TI - Typhus fever in Iran and Iraq, 1942-43; a report on 2,859 cases. PMID- 21014990 TI - [Not Available]. PMID- 21014992 TI - A survey of the activities of the Military Isolation Hospital, Aldershot, 1939 1945. PMID- 21014993 TI - Poliomyelitis in West Africa. PMID- 21014994 TI - Some medico-social problems of mental dullness in the Army. PMID- 21014995 TI - Training notes from Burma. PMID- 21014996 TI - The management of convalescent neurotics at the Neurosis Wing, 101 Military Convalescent Depot. PMID- 21014997 TI - Smile therapy. PMID- 21014998 TI - Penicillin in 100 cases of early syphilis. PMID- 21014999 TI - A case of traumatic rupture of a hydronephrotic kidney. PMID- 21015000 TI - [Not Available]. PMID- 21015002 TI - [Not Available]. PMID- 21015001 TI - [Not Available]. PMID- 21015003 TI - [Not Available]. PMID- 21015004 TI - [Not Available]. PMID- 21015005 TI - [Not Available]. PMID- 21015006 TI - [Not Available]. PMID- 21015007 TI - [Not Available]. PMID- 21015008 TI - [Not Available]. PMID- 21015009 TI - [Not Available]. PMID- 21015010 TI - [Not Available]. PMID- 21015011 TI - [Not Available]. PMID- 21015012 TI - [Not Available]. PMID- 21015013 TI - [Not Available]. PMID- 21015014 TI - [Not Available]. PMID- 21015015 TI - [Not Available]. PMID- 21015016 TI - [Not Available]. PMID- 21015017 TI - [Not Available]. PMID- 21015018 TI - [Not Available]. PMID- 21015019 TI - [Not Available]. PMID- 21015020 TI - [Not Available]. PMID- 21015021 TI - [Not Available]. PMID- 21015022 TI - [Not Available]. PMID- 21015023 TI - [Not Available]. PMID- 21015024 TI - [Not Available]. PMID- 21015025 TI - [Not Available]. PMID- 21015026 TI - [Not Available]. PMID- 21015027 TI - [Not Available]. PMID- 21015028 TI - [Not Available]. PMID- 21015029 TI - [Not Available]. PMID- 21015030 TI - [Not Available]. PMID- 21015031 TI - [Not Available]. PMID- 21015032 TI - [Not Available]. PMID- 21015033 TI - [Not Available]. PMID- 21015034 TI - [Not Available]. PMID- 21015035 TI - [Not Available]. PMID- 21015036 TI - [Not Available]. PMID- 21015037 TI - [Not Available]. PMID- 21015038 TI - [Not Available]. PMID- 21015039 TI - [Not Available]. PMID- 21015040 TI - [Not Available]. PMID- 21015041 TI - [Not Available]. PMID- 21015042 TI - [Not Available]. PMID- 21015043 TI - [Not Available]. PMID- 21015044 TI - [Not Available]. PMID- 21015045 TI - [Not Available]. PMID- 21015046 TI - [Not Available]. PMID- 21015047 TI - [Not Available]. PMID- 21015048 TI - [Not Available]. PMID- 21015049 TI - [Not Available]. PMID- 21015050 TI - [Not Available]. PMID- 21015051 TI - [Not Available]. PMID- 21015052 TI - [Not Available]. PMID- 21015053 TI - [Not Available]. PMID- 21015054 TI - [Not Available]. PMID- 21015055 TI - [Not Available]. PMID- 21015057 TI - [Not Available]. PMID- 21015056 TI - [Not Available]. PMID- 21015058 TI - [Not Available]. PMID- 21015059 TI - [Not Available]. PMID- 21015060 TI - [Not Available]. PMID- 21015061 TI - [Not Available]. PMID- 21015062 TI - [Not Available]. PMID- 21015063 TI - [Not Available]. PMID- 21015064 TI - [Not Available]. PMID- 21015065 TI - [Not Available]. PMID- 21015066 TI - [Not Available]. PMID- 21015067 TI - [Not Available]. PMID- 21015068 TI - [Not Available]. PMID- 21015069 TI - [Not Available]. PMID- 21015070 TI - [Not Available]. PMID- 21015071 TI - [Not Available]. PMID- 21015072 TI - [Not Available]. PMID- 21015073 TI - [Not Available]. PMID- 21015074 TI - [Not Available]. PMID- 21015075 TI - [Not Available]. PMID- 21015076 TI - [Not Available]. PMID- 21015077 TI - [Not Available]. PMID- 21015078 TI - [Not Available]. PMID- 21015079 TI - The inhibition by cysteine and glycine of the deterioration of dried egg white. PMID- 21015080 TI - Notes on some variations in field bindweed (Convolvulus arvensis L.). PMID- 21015081 TI - The release of atomic energy. PMID- 21015082 TI - SCIENTIFIC research and industrial planning; British Association Conference. PMID- 21015083 TI - Scientific centenaries in 1946. PMID- 21015084 TI - A new method for the separation of the amylose and amylopectin components of starch. PMID- 21015086 TI - Seasonal cycle and inversion frequency in populations. PMID- 21015085 TI - Suspected copper deficiency in cattle in Aberdeenshire. PMID- 21015087 TI - Red, brown and green pigment in leguminous root nodules. PMID- 21015088 TI - The Lister Institute of Preventive Medicine. PMID- 21015089 TI - MICRO-ORGANISMS and their environment. PMID- 21015090 TI - Biological stimulation in germination. PMID- 21015091 TI - Bacterial cellulose for osmometer membranes. PMID- 21015092 TI - New ultra-violet band-systems of SiS, SiSe and SiTe. PMID- 21015093 TI - Production of capons by the use of synthetic oestrogens. PMID- 21015094 TI - Fructose, a constituent of semen. PMID- 21015095 TI - Investigation of insecticidal sprays. PMID- 21015096 TI - Historical development of the betatron. PMID- 21015097 TI - Microbiology, biochemistry, and the genetics of microorganisms. PMID- 21015098 TI - International scientific co-operation. PMID- 21015100 TI - Carriage of plague by the common brown rat (Rattus norvegicus). PMID- 21015099 TI - Identification of aminobenzoic acids in relation to bacterial metabolism. PMID- 21015101 TI - Tritanopia and colour vision. PMID- 21015102 TI - Nicotinic acid in sugary and starchy maize. PMID- 21015103 TI - Anthropology in Portugal. PMID- 21015104 TI - The background of Rontgen's discovery. PMID- 21015105 TI - Progress of x-ray analysis of organic and fibre structures. PMID- 21015106 TI - X-ray diffraction in inorganic chemistry, metallurgy and mineralogy. PMID- 21015107 TI - Relational plant morphology. PMID- 21015108 TI - Photometric record of the mode of action of penicillin and dagenan in association. PMID- 21015109 TI - Dehydrodoisynolic acid and its clinical use. PMID- 21015111 TI - Determination of order parameters from the x-ray diffraction effect. PMID- 21015110 TI - A new method of phosphorylation. PMID- 21015112 TI - Fine structure and mechanism of division of the nuclei of the bacterium Caryophanon latum. PMID- 21015113 TI - Atomic energy as a human asset. PMID- 21015114 TI - Radio-frequency energy from the sun. PMID- 21015115 TI - Structure of isoprene. PMID- 21015116 TI - Relationship between the antigens of blood and skin. PMID- 21015117 TI - Mutations in Drosophila after chemical treatment of gonads in vitro. PMID- 21015118 TI - Anti-tadpole sera. PMID- 21015119 TI - Johann Pharamund Rhumelius. PMID- 21015120 TI - Science and technology in China's far south-east. PMID- 21015121 TI - Nutrition in Japan. PMID- 21015123 TI - NATIONAL flour (80 per cent extraction) and bread in Britain. PMID- 21015122 TI - Oxidation. PMID- 21015124 TI - Synthesis of some compounds possessing vitamin A activity. PMID- 21015125 TI - Direct synthesis of hydrazoic acid. PMID- 21015126 TI - Spreading of boundaries in electrophoresis. PMID- 21015127 TI - Secretion of pepsin in achlorhydric human subjects after injection of histamine. PMID- 21015128 TI - Menarche, growth and physical efficiency. PMID- 21015129 TI - Authenticity of scientific anecdotes. PMID- 21015130 TI - FRENCH ASSOCIATION for the Advancement of Science. PMID- 21015135 TI - [Not Available]. PMID- 21015136 TI - [Not Available]. PMID- 21015137 TI - [Not Available]. PMID- 21015138 TI - The neutron, the intermediate or compound nuclous, and the atomic bomb. PMID- 21015139 TI - The effect of B-pyracin and the Lactobacillus casei factor upon hemoglobin regeneration following hemorrhage. PMID- 21015140 TI - The site of action of DDT in the cockroach. PMID- 21015141 TI - Molecular weights and other properties of viruses as determined by light absorption. PMID- 21015142 TI - Transmission of papaya bunchy top by a leaf hopper of the genus Empoasca. PMID- 21015143 TI - Sunshine and the atomic bomb. PMID- 21015144 TI - Social parasites among birds. PMID- 21015145 TI - Basic English for science. PMID- 21015146 TI - Let's hear about it. PMID- 21015147 TI - The use of atomic trail blazers in physiological investigations with plants. PMID- 21015148 TI - The function of drawings and the meaning of the creative spell in a schizophrenic artist. PMID- 21015149 TI - Telepathy and problems of psychoanalysis. PMID- 21015150 TI - Psychoanalysis and history; the Nibelungs and the Bible. PMID- 21015151 TI - Processing and caring for prisoners of war. PMID- 21015153 TI - Extending our library facilities by adding a cultural and recreational collection. PMID- 21015152 TI - International influences on nursing in Finland. PMID- 21015154 TI - The treatment of thermal burns. PMID- 21015155 TI - ARE hospitals made for people, or vice versa? PMID- 21015156 TI - The armed services and the nursing profession. PMID- 21015157 TI - The child with active rheumatic fever and her nursing care. PMID- 21015158 TI - NURSING with the TVA. PMID- 21015160 TI - Diabetes mellitus. PMID- 21015159 TI - Understanding the adolescent; the adolescent and his emotional reaction to illness. PMID- 21015161 TI - The diabetic and the hospital nurse. PMID- 21015162 TI - The diabetic, from a public health viewpoint. PMID- 21015163 TI - The care of the premature baby. PMID- 21015164 TI - Techniques of interviewing. PMID- 21015165 TI - Industrial nutrition programs; the nurse's role. PMID- 21015166 TI - Supervision in industrial nursing; management and promotion of efficiency. PMID- 21015167 TI - Manufacturers' health clinic. PMID- 21015168 TI - Venereal disease control program in industry. PMID- 21015169 TI - Tuberculosis in industry; the nurse and follow-up. PMID- 21015170 TI - Injuries to the rectum and their nursing care. PMID- 21015171 TI - Reconsideration of nursing; its fundamentals, purpose and place in the community, the period of professional maturity. PMID- 21015172 TI - Hormones in human reproduction; progesterone. PMID- 21015173 TI - Delivery of a thoracopagus monster. PMID- 21015174 TI - Rare diseases of returning service men; leishmaniasis. PMID- 21015175 TI - Our hospital systems, a retrospect and a prospect. PMID- 21015176 TI - Liverpool Institute of Research for the Prevention of Disease. PMID- 21015177 TI - PRE-NURSING course. PMID- 21015178 TI - The treatment of pneumococcal meningitis with penicillin. PMID- 21015179 TI - Aids to memory. PMID- 21015180 TI - HOME to health in the Soviet Union; the Red Army's way with battle casualties. PMID- 21015181 TI - ROMANCE of drugs; from Empire plants; deadly nightshade (Atropa belladonna). PMID- 21015182 TI - And it's an exciting future! PMID- 21015183 TI - Looking at industrial nursing. PMID- 21015184 TI - School health: whose job is it? PMID- 21015185 TI - Public health nurse in the rural school. PMID- 21015186 TI - Nurse interview in the tuberculosis clinic. PMID- 21015187 TI - Staff education; old concepts in a changing situation. PMID- 21015188 TI - CONSERVATION of hearing in school children. PMID- 21015189 TI - Technical refinements in the removal of magnetic foreign bodies from the posterior segment of the eye. PMID- 21015190 TI - The ocular complications of leprosy. PMID- 21015191 TI - Concentration of penicillin in the aqueous humor following systemic administration. PMID- 21015192 TI - Fascia-lata transplant for retrotarsal atrophy of upper lid following enucleation. PMID- 21015193 TI - Nonperforating cyclodiathermy for the treatment of glaucoma. PMID- 21015194 TI - Stevens-Johnson's disease. PMID- 21015195 TI - Congenital glaucoma following maternal rubella; report of two cases. PMID- 21015196 TI - Heterogeneous conjunctival transplantation. PMID- 21015197 TI - A continuation of the screen test. PMID- 21015198 TI - Note on the incidence of clinically significant aniseikonia. PMID- 21015199 TI - Visual exercises in ophthalmology. PMID- 21015200 TI - Examination and correction of astigmatism. PMID- 21015201 TI - Central myopic degeneration or central retinal vascular disease. PMID- 21015202 TI - Deep tuberculous keratitis treated with beta emanation. PMID- 21015203 TI - Acquired ptosis, classification and correction. PMID- 21015204 TI - Infection of the human eye with Torula histolytica. PMID- 21015205 TI - Problems of postwar ophthalmalogic training. PMID- 21015206 TI - The eye and its nutrition. PMID- 21015207 TI - What is orthoptics? PMID- 21015208 TI - Irradiation of the eustachian tube; an anatomic, physical and clinical study of a treatment for recurrent otitis media applied to aero-otitis. PMID- 21015209 TI - Clinical use of penicillin in infections of the ears, nose and throat. PMID- 21015210 TI - Transtubal instillation of penicillin in acute otitis media. PMID- 21015211 TI - Penicillin in otolaryngologic practice. PMID- 21015212 TI - Laryngeal neurosis incident to military service. PMID- 21015213 TI - An evaluation of the Lempert fenestra nov-ovalis operation in the treatment of otosclerosis. PMID- 21015214 TI - Tissue changes produced in the nasal mucous membrane of normal mice by prolonged local administration of some solutions containing sulfonamide compounds. PMID- 21015215 TI - Histologic observations on the healing of labyrinthine fistulas in monkeys. PMID- 21015216 TI - Bronchoscopy as an aid in the diagnosis and treatment of allergic pulmonary disease. PMID- 21015217 TI - Clinical results in patients treated by intranasal ethmoidectomy. PMID- 21015218 TI - A modification of the extralaryngeal approach to arytenoidectomy for bilateral abductor paralysis. PMID- 21015219 TI - Surgical treatment of chronic frontal sinusitis. PMID- 21015220 TI - Bacterial thrombophlebitis of a cavernous sinus with recovery. PMID- 21015221 TI - Allergy. PMID- 21015222 TI - A practical approach to the selection of hearing aids. PMID- 21015223 TI - A method of classifying employees for selective placement. PMID- 21015224 TI - Plant experience with metalic stencils. PMID- 21015225 TI - PLANT experience; hosiery mill medical department. PMID- 21015226 TI - Congenital hypertrophic pyloric stenosis; review of 30 cases. PMID- 21015227 TI - Dysmenorrhea and physical education. PMID- 21015228 TI - Stuttering. PMID- 21015229 TI - Rheumatic fever as a cause of abdominal pain in children. PMID- 21015230 TI - Diagnosis of tuberculous bronchopneumonia in children. PMID- 21015231 TI - Supraglottic edema; influenza. PMID- 21015232 TI - Acute poliomyelitis with encephalitis. PMID- 21015233 TI - [Not Available]. PMID- 21015234 TI - [Not Available]. PMID- 21015235 TI - [Not Available]. PMID- 21015236 TI - [Not Available]. PMID- 21015237 TI - [Not Available]. PMID- 21015238 TI - [Not Available]. PMID- 21015239 TI - [Not Available]. PMID- 21015240 TI - [Not Available]. PMID- 21015241 TI - [Not Available]. PMID- 21015242 TI - [Not Available]. PMID- 21015243 TI - [Not Available]. PMID- 21015244 TI - [Not Available]. PMID- 21015245 TI - [Not Available]. PMID- 21015246 TI - [Not Available]. PMID- 21015247 TI - [Not Available]. PMID- 21015248 TI - [Not Available]. PMID- 21015249 TI - [Not Available]. PMID- 21015250 TI - [Not Available]. PMID- 21015251 TI - [Not Available]. PMID- 21015252 TI - [Not Available]. PMID- 21015253 TI - [Not Available]. PMID- 21015254 TI - [Not Available]. PMID- 21015255 TI - [Not Available]. PMID- 21015256 TI - [Not Available]. PMID- 21015257 TI - [Not Available]. PMID- 21015258 TI - [Not Available]. PMID- 21015259 TI - [Not Available]. PMID- 21015260 TI - [Not Available]. PMID- 21015261 TI - [Not Available]. PMID- 21015262 TI - [Not Available]. PMID- 21015263 TI - Convulsions in infancy and childhood. PMID- 21015264 TI - Multiple tumors; anorexia; vomiting. [melanoma]. PMID- 21015265 TI - Vomiting; diarrhea. [genitourinary tract abnormality]. PMID- 21015266 TI - Vomiting; fever; sore throat; cough. [emphysema]. PMID- 21015267 TI - Swelling of left cheek. [parotitis]. PMID- 21015268 TI - [Not Available]. PMID- 21015269 TI - [Not Available]. PMID- 21015270 TI - [Not Available]. PMID- 21015271 TI - [Not Available]. PMID- 21015272 TI - [Not Available]. PMID- 21015273 TI - [Not Available]. PMID- 21015274 TI - [Not Available]. PMID- 21015275 TI - [Not Available]. PMID- 21015276 TI - [Not Available]. PMID- 21015277 TI - [Not Available]. PMID- 21015278 TI - [Not Available]. PMID- 21015279 TI - [Not Available]. PMID- 21015280 TI - [Not Available]. PMID- 21015281 TI - [Not Available]. PMID- 21015282 TI - [Not Available]. PMID- 21015283 TI - [Not Available]. PMID- 21015284 TI - [Not Available]. PMID- 21015285 TI - [Not Available]. PMID- 21015286 TI - [Not Available]. PMID- 21015287 TI - [Not Available]. PMID- 21015288 TI - [Not Available]. PMID- 21015289 TI - [Not Available]. PMID- 21015290 TI - [Not Available]. PMID- 21015291 TI - [Not Available]. PMID- 21015292 TI - [Not Available]. PMID- 21015293 TI - [Not Available]. PMID- 21015295 TI - [Not Available]. PMID- 21015294 TI - [Not Available]. PMID- 21015296 TI - Hops. PMID- 21015297 TI - Fuchsias and fashions; an early Victorian indictment; new lamps for old. PMID- 21015298 TI - Public administration in relation to the nature and purpose of the modern social service State. PMID- 21015299 TI - FAULTY prescription; New Zealand doctor fined. PMID- 21015300 TI - Some recent advances in chromatography. PMID- 21015302 TI - The Chemical nature of penicillin. PMID- 21015301 TI - Permanent waving and the structure of the hair. PMID- 21015303 TI - The histology of belladonna root; differential characters for the powder. PMID- 21015304 TI - Investigations on the autoxidation of diethyl ether; a quantitative determination of the autoxidation products. PMID- 21015305 TI - The effect of freezing on the potency of tetanus antitoxin. PMID- 21015307 TI - The stability of tetanus antitoxin. PMID- 21015306 TI - The stability of the three gas gangrene antitoxins, perfringens, Vibrion septique and oedematiens, under different conditions of storage. PMID- 21015308 TI - The stability of refined antitoxin. PMID- 21015309 TI - A note on the freezing of solutions of refined antitoxin. PMID- 21015310 TI - A note on the deterioration of diphtheria and tetanus antitoxins. PMID- 21015311 TI - The estimation of thyroxine iodine in thyroid gland powder. PMID- 21015312 TI - The effect of activity upon learning and retention in the cockroach, Periplaneta americana. PMID- 21015313 TI - Cortical and midbrain mediation of a conditioned discrimination of acoustic intensities. PMID- 21015314 TI - Color adaptation of the human eye. PMID- 21015315 TI - The binocular depth contrast phenomenon. PMID- 21015316 TI - Discrimination of auditory intensities in the cat. PMID- 21015317 TI - Dependence of scotopic perception of form upon distance. PMID- 21015318 TI - Minimal clues in the peak-of-tension procedure for determining guilt. PMID- 21015319 TI - A nomograph for the Brunswick ratio. PMID- 21015320 TI - A convenient alternating current circuit for measuring GSR's. PMID- 21015322 TI - TOOLS and terms in recent researches. PMID- 21015321 TI - The Kohler effect. PMID- 21015323 TI - An attempt at experimental approach to the psychology of religion. PMID- 21015324 TI - A comparative study of annoyances. PMID- 21015325 TI - Reward and punishment in learning. PMID- 21015326 TI - Personality structure and measurement; the operational determination of trait unities. PMID- 21015328 TI - A color aptitude test, 1940 experimental edition. PMID- 21015327 TI - The Psychological Corporation's index of public opinion. PMID- 21015329 TI - Statistical analysis of an industrial rating chart. PMID- 21015330 TI - A simplified form for reporting test results. PMID- 21015331 TI - A comparison of the reliability and performance for the Minnesota rate of manipulation test for subjects tested individually and in groups of two. PMID- 21015332 TI - Use of the Shipley-Hartford test in evaluating intellectual functioning of neuropsychiatric patients. PMID- 21015333 TI - A social I.E. scale for the Minnesota multiphasic personality inventory. PMID- 21015334 TI - A comparison of the Thurstone and Likert techniques of attitude scale construction. PMID- 21015335 TI - The economy of item analysis with the IBM graphic item counter. PMID- 21015337 TI - The effect of adaptation to the unconditioned stimulus upon the formation of conditioned avoidance responses. PMID- 21015336 TI - The interrelationship of visual acuity at different distances. PMID- 21015338 TI - Studies in spatial learning: Orientation and the short-cut. PMID- 21015339 TI - How a person establishes a scale for evaluating his performance. PMID- 21015340 TI - Effects of anoxia on performance at several simulated altitudes. PMID- 21015341 TI - The effect of chronological age on aesthetic preferences for rectangles of different proportions. PMID- 21015342 TI - An empirical test of a derived measure of changes in skin resistance. PMID- 21015343 TI - Factors influencing the learning and retention of concepts; the influence of set. PMID- 21015344 TI - An attempt to correlate the occipital alpha frequency of the electroencephalogram with performance on a mental ability test. PMID- 21015345 TI - Note on subjects used in standardizing a railwalking test and the ataxiagraph. PMID- 21015346 TI - Jung's psychological types, their frequency of occurrence. PMID- 21015347 TI - A quantitative approach to the study of responses of psychotics in the completion of figures involving visual and motor components. PMID- 21015348 TI - Basal metabolism and the college freshman psychological test. PMID- 21015349 TI - Respiration and blood pressure in sensory motor conflict. PMID- 21015350 TI - A method of rating animal intelligence. PMID- 21015351 TI - An improved technique for studying the conditioned squeak reaction in hooded rats. PMID- 21015352 TI - Different responses produced by good and poor art. PMID- 21015353 TI - Some comments on Marion Barlett's Suggestibility in dementia praecox paranoid patients. PMID- 21015354 TI - The anal military. PMID- 21015355 TI - [Not Available]. PMID- 21015356 TI - [Not Available]. PMID- 21015357 TI - [Not Available]. PMID- 21015358 TI - [Not Available]. PMID- 21015359 TI - [Not Available]. PMID- 21015360 TI - [Not Available]. PMID- 21015361 TI - [Not Available]. PMID- 21015362 TI - [Not Available]. PMID- 21015363 TI - [Not Available]. PMID- 21015364 TI - Syphilis survey in Cojutepeque, El Salvador. PMID- 21015365 TI - Dried blood plasma available. PMID- 21015366 TI - Infant mortality in Connecticut, 1935-1944. PMID- 21015367 TI - How does your community measure up to sanitation standards? PMID- 21015368 TI - Poliomyelitis in the light of recent experimental work. PMID- 21015369 TI - Hydatid disease in Victoria. PMID- 21015370 TI - A survey of the dogs in the Shire of Heytesbury for Echinococcus granulosus; the mature tapeworm of the dog which causes hydatid disease in man and animals. PMID- 21015371 TI - Anthrax. PMID- 21015372 TI - Ante-natal care. PMID- 21015373 TI - The pre-school movement and the community. PMID- 21015374 TI - FIRES SHOW dry cleaning in home to be dangerous. PMID- 21015375 TI - Diagnosis of malaria; notes on the preparation and staining of thin and thick blood films, for the detection of malarial parasites. PMID- 21015376 TI - War and the nutritional state. PMID- 21015377 TI - Typhoid fever: brief account of a small outbreak in Northamptonshire. PMID- 21015378 TI - A preliminary report on a modification of the Kahn test. PMID- 21015379 TI - BIRTH rates and education. PMID- 21015380 TI - Typhus fever. PMID- 21015381 TI - Laboratory diagnosis of typhus and prophylactic vaccination. PMID- 21015383 TI - Some typhus case histories. PMID- 21015382 TI - Some entomological aspects of typhus. PMID- 21015384 TI - Cancer act planning. PMID- 21015385 TI - The future of the laboratory services for Britain. PMID- 21015386 TI - Rehabilitation and aftercare in tuberculosis. PMID- 21015387 TI - Photofluorographic roll-film viewers. PMID- 21015388 TI - Tuberculosis mortality in major cities: United States, 1942-43. PMID- 21015389 TI - The incidence of poliomyelitis and its crippling effects as recorded in family surveys. PMID- 21015390 TI - Responsibility for accidents in radiological departments. PMID- 21015391 TI - Effective atomic number and energy absorption in tissues. PMID- 21015392 TI - Anaerobic cellulitis, due to perforation of the colon; a case report with an illustration of the radiographic appearances. PMID- 21015393 TI - Duplication of radiography by solarisation. PMID- 21015394 TI - The localisation of foreign bodies in the chest; a practical report. PMID- 21015395 TI - The anatomy of the blood vessels of the human lung as applied to chest radiology; changes in the lung vascular tree in disease processes. PMID- 21015396 TI - The anatomy of the blood vessels of the human lung as applied to chest radiology; emphysema and asthma. PMID- 21015397 TI - Ovarian dermoid cysts. PMID- 21015398 TI - The evolution of radiography. PMID- 21015400 TI - Pneumo-arthrography in the Navy. PMID- 21015399 TI - What is a line? PMID- 21015401 TI - Some experiences in running a mass radiography unit. PMID- 21015402 TI - [Not Available]. PMID- 21015403 TI - [Not Available]. PMID- 21015404 TI - [Not Available]. PMID- 21015405 TI - [Not Available]. PMID- 21015406 TI - [Not Available]. PMID- 21015407 TI - [Not Available]. PMID- 21015409 TI - [Not Available]. PMID- 21015408 TI - [Not Available]. PMID- 21015410 TI - On the treatment of Dupuytren's contracture. PMID- 21015411 TI - Sacral dermoid cysts; especially with a view to their treatment. PMID- 21015412 TI - Rupture of the aponeurosis of the shoulder joint, particularly referring to its treatment. PMID- 21015413 TI - Investigations of postoperative shock; haemoconcentration, plasma protein and blood electrolytes after gastrectomy. PMID- 21015414 TI - Liver changes in surgical conditions. PMID- 21015415 TI - Vesicovaginal fistula: an improvement in the Chaffin method of postoperative treatment, using Chaffin suction drainage. PMID- 21015416 TI - Effect of parenternal saline solution on wound healing. PMID- 21015417 TI - Early amputation following surgery. PMID- 21015418 TI - Obscure causes of intra-abdominal hemorrhage. PMID- 21015419 TI - Arthrotomy approaches in the lower extremity. PMID- 21015420 TI - Localized back pain. PMID- 21015421 TI - Deaths from surgical diseases of the biliary tract. PMID- 21015422 TI - Subtotal gastrectomy in the treatment of ulcer. PMID- 21015423 TI - March fractures of the foot; care and management of 692 patients. PMID- 21015424 TI - Psychosomatic symptoms and borderline hyperthyroidism. PMID- 21015425 TI - Use of a double roll as a bandage. PMID- 21015426 TI - Fracture of the clavicle; a simple method by means of which the patient holds his own shoulders backward and upward. PMID- 21015427 TI - Supernumerary kidney with ureter opening into vagina. PMID- 21015428 TI - Non-specific regional jejunitis. PMID- 21015429 TI - Multiple parathyroid adenomas; three operative explorations with removal of two tumors. PMID- 21015430 TI - Sarcoma of the rectum. PMID- 21015431 TI - The use of a guide suture in strangulated hernia. PMID- 21015432 TI - Diagnosis of lacerated spleen. PMID- 21015433 TI - Conservative treatment of a chronic amebic liver abscess complicated by rupture and an intraperitoneal abscess. PMID- 21015434 TI - Granuloma inguinale (venereum) of uterus. PMID- 21015435 TI - Regional ileitis; report of an asymptomatic lethal case. PMID- 21015436 TI - Carcinoid tumor of the appendix producing a mucocele. PMID- 21015437 TI - Appendico-ileal fistula. PMID- 21015438 TI - Toothpick in a perinephric abscess. PMID- 21015439 TI - Annular pancreas causing duodenal obstruction. PMID- 21015440 TI - New instruments in rhinoplastic surgery. PMID- 21015441 TI - A self-retaining hemi-laminectomy retractor. PMID- 21015442 TI - Rat trap retractors. PMID- 21015444 TI - Pilonidal sinus and cyst. PMID- 21015443 TI - Arteriovenous aneurysms of the scalp and face. PMID- 21015445 TI - Effect of intravenous administration of oxygen on shock in dogs and in human beings. PMID- 21015446 TI - Study of gastric lesions by means of biopsy specimens removed endoscopically. PMID- 21015447 TI - Diverticula of the stomach. PMID- 21015448 TI - Fractures. PMID- 21015449 TI - Conditions involving the spine and thorax, exclusive of those in the lower part of the back. PMID- 21015450 TI - [Not Available]. PMID- 21015451 TI - [Not Available]. PMID- 21015452 TI - [Not Available]. PMID- 21015453 TI - [Not Available]. PMID- 21015454 TI - [Not Available]. PMID- 21015455 TI - [Not Available]. PMID- 21015456 TI - [Not Available]. PMID- 21015457 TI - [Not Available]. PMID- 21015458 TI - Pentothal sodium anesthesia using automatic control syringe method. PMID- 21015460 TI - Surgical removal of displaced third molar crown. PMID- 21015459 TI - Submaxillary adenitis, embedded teeth and deviation deformity of the mandible. PMID- 21015461 TI - Neuroma of palate; report of a case. PMID- 21015462 TI - Osteoma of the mandibular condyle with deviation prognathic deformity. PMID- 21015463 TI - Mandibular osteomyelitis: its diagnosis and treatment. PMID- 21015464 TI - Care of the surgical patient. PMID- 21015465 TI - Compound composite odontome of the mandible. PMID- 21015466 TI - Osteogenic sarcoma of the maxilla. PMID- 21015467 TI - Surgical treatment of mandibular prognathism. PMID- 21015468 TI - The management of war wounds of the chest in a base center; the role of early pulmonary decortication. PMID- 21015469 TI - A review of the activities of the thoracic center for the III and IV hospital groups, 160th General Hospital European Theater of Operations, June 10, 1944 to Jan. 1, 1945. PMID- 21015470 TI - Military thoracic surgery in the forward area. PMID- 21015471 TI - Experience in the localization of thoracic foreign bodies. PMID- 21015472 TI - [Anaphylactic shock in intravenous infusions of antigangrene serum]. PMID- 21015473 TI - [The treatment of wounds with chloracid]. PMID- 21015474 TI - [Chlorethylidene methylene narcosis]. PMID- 21015475 TI - [Secondary sutures and epidermal plastics at the front]. PMID- 21015476 TI - [The treatment of congelations]. PMID- 21015477 TI - [Pericarditis following gunshot injuries of the thorax]. PMID- 21015478 TI - [On the clinics of blind wounds of the heart]. PMID- 21015479 TI - [Contribution to the surgical treatment of combined affections of the peripheral nerves and bones]. PMID- 21015480 TI - [Larger surgical access in gunshot wounds of the plexus brachialis]. PMID- 21015481 TI - [Experience in the treatment of gunshot damages of the joints]. PMID- 21015482 TI - [A modification of Kirschner's operation]. PMID- 21015483 TI - [Supraclavicular and subclavicular infiltrations of novocaine as a method of vagosympathetic block]. PMID- 21015484 TI - [On the ligature of the fistulae in amputation stumps]. PMID- 21015485 TI - [A case of removal of a bullet from the heart]. PMID- 21015486 TI - [Suture of the lower trachea]. PMID- 21015487 TI - [Not Available]. PMID- 21015488 TI - [Not Available]. PMID- 21015490 TI - [Not Available]. PMID- 21015489 TI - [Not Available]. PMID- 21015491 TI - [Not Available]. PMID- 21015492 TI - [Not Available]. PMID- 21015493 TI - [Not Available]. PMID- 21015494 TI - [Not Available]. PMID- 21015495 TI - [Not Available]. PMID- 21015496 TI - [Not Available]. PMID- 21015497 TI - The early management of facial injuries. PMID- 21015498 TI - Pedicle grafts from the arm for reconstructions about the face. PMID- 21015500 TI - The technic of lumbar sympathectomy. PMID- 21015499 TI - The repair of skull defects with special reference to the use of tantalum. PMID- 21015501 TI - Hemilaminectomy. PMID- 21015502 TI - Spinal puncture. PMID- 21015503 TI - The technic of thyroidectomy. PMID- 21015504 TI - Neck dissections; indications and technics. PMID- 21015505 TI - Diagnosis and treatment of carcinoma of the female breast. PMID- 21015507 TI - Clinic on pneumonectomy, stressing the technic of operation. PMID- 21015506 TI - Surgery of the mediastinum. PMID- 21015508 TI - The surgical repair in various types of diaphragmatic hernia. PMID- 21015509 TI - Surgical treatment of malignant tumors of the duodenum exclusive of those arising from the papilla of Vater. PMID- 21015510 TI - Primary resections of the colon with special reference to surgical diagnosis and management. PMID- 21015511 TI - Technical details in the management of the duodenum in gastric resection. PMID- 21015512 TI - The technic of cholecystectomy and cholecystostomy. PMID- 21015513 TI - Treatment of fractures of the hip; surgical technic. PMID- 21015514 TI - Technic of debridement of the knee joint for arthritis. PMID- 21015515 TI - Interruption of the sympathetic nervous system in relation to trauma. PMID- 21015516 TI - Abdominal apoplexy secondary to ruptured congenital aneurysm. PMID- 21015517 TI - Penicillin therapy of infections in 220 patients. PMID- 21015518 TI - A safety factor in gastric resection. PMID- 21015519 TI - Hyperuricemia in gastric cancer. PMID- 21015520 TI - Multiple carcinomas of the stomach. PMID- 21015521 TI - Early diagnosis and management of small intestinal obstruction. PMID- 21015522 TI - Fissures of the articular cartilage of the patella. PMID- 21015523 TI - Inguinal hernias and allied defects in naval recruits. PMID- 21015524 TI - The use of chemotherapy in the secondary closure of war wounds of soft parts. PMID- 21015525 TI - Sympathectomy and the circulation; anatomic and physiologic considerations and early and late limitations. PMID- 21015526 TI - Menstrual dysfunctions; abnormal uterine bleeding. PMID- 21015527 TI - Recent advances in pediatric pathology; jaundice in childhood. PMID- 21015528 TI - Caudal analgesia with the aid of a new appliance. PMID- 21015530 TI - Trichomoniasis; a 12 year study. PMID- 21015531 TI - Gastric adenomas; a pathologic study. PMID- 21015529 TI - Oxytocic action of methergine; a synthetic ergonovine. PMID- 21015532 TI - Rehabilitation of the disabled; a sociological study. PMID- 21015533 TI - Electrical convulsion therapy: apparatus and indications for its use. PMID- 21015534 TI - A colliery medical service in practice. PMID- 21015535 TI - Sepsis and the physiotherapist. PMID- 21015536 TI - The control of lung disease in industry. PMID- 21015537 TI - Oral sepsis and its treatment. PMID- 21015538 TI - ETALATE: a superior sclerosing agent. PMID- 21015539 TI - CLINICAL use of carbrital. PMID- 21015540 TI - Surgical technique in thoracoplasty with particular reference to sepsis. PMID- 21015541 TI - Pulmonary tuberculosis and pregnancy. PMID- 21015542 TI - Observations on myotatic irritability. PMID- 21015543 TI - [Not Available]. PMID- 21015544 TI - [Not Available]. PMID- 21015545 TI - [Not Available]. PMID- 21015546 TI - [Not Available]. PMID- 21015547 TI - [Not Available]. PMID- 21015548 TI - [Not Available]. PMID- 21015549 TI - [Not Available]. PMID- 21015550 TI - [Not Available]. PMID- 21015551 TI - [Not Available]. PMID- 21015552 TI - [Not Available]. PMID- 21015553 TI - [Not Available]. PMID- 21015554 TI - [Not Available]. PMID- 21015556 TI - [Not Available]. PMID- 21015555 TI - [Not Available]. PMID- 21015557 TI - [Not Available]. PMID- 21015558 TI - [Not Available]. PMID- 21015559 TI - [Not Available]. PMID- 21015560 TI - [Not Available]. PMID- 21015561 TI - Tuberculosis in France during the war. PMID- 21015562 TI - Mass radiography in India. PMID- 21015563 TI - The present status of unilateral renal hypertension. PMID- 21015564 TI - Nephroptosis with co-existing lesions. PMID- 21015565 TI - Some improvements in the technique of ureterocystostomy. PMID- 21015566 TI - Giant hydronephrosis in a duplicated kidney. PMID- 21015567 TI - Wilms' tumor in 75 year old male; report of a case. PMID- 21015568 TI - Crossed renal ectopia with fusion. PMID- 21015570 TI - Malacoplakia of the bladder. PMID- 21015569 TI - Congenital solitary pelvic kidney. PMID- 21015571 TI - Open x-ray therapy in carcinoma of the bladder. PMID- 21015572 TI - Diverticular or cavitary chronic prostatitis. PMID- 21015573 TI - Fistula of the penile urethra; a method of repair utilizing stainless steel pull out sutures. PMID- 21015574 TI - Circumcision for adults. PMID- 21015575 TI - Urinary extravasation; report of a case treated by penicillin and operation. PMID- 21015576 TI - Unilateral scrotal swelling following blast injury; a syndrome. PMID- 21015577 TI - Primary sarcoma of prostate gland in a soldier. PMID- 21015578 TI - A clinico-pathological study of 100 female urethras. PMID- 21015579 TI - Penicillin therapy for sulfonamide resistant gonorrhea. PMID- 21015580 TI - [Not Available]. PMID- 21015581 TI - [Not Available]. PMID- 21015582 TI - [Not Available]. PMID- 21015583 TI - A plan for revitalizing national venereal disease control. PMID- 21015584 TI - Untreated syphilis in the male Negro; mortality during 12 years of observation. PMID- 21015585 TI - The effect of treated acquired syphilis on life expectancy. PMID- 21015586 TI - Mortality trends for syphilis. PMID- 21015587 TI - USE of sulphonamides in outbreaks of acute coccidiosis in chicks. PMID- 21015588 TI - Infectious rhinitis in swine (bull nose). PMID- 21015589 TI - Poultry diseases common to farm flocks. PMID- 21015590 TI - Scrapie; a disease of sheep; a review of the literature. PMID- 21015591 TI - Induction of estrus in lactating sows with equine gonadotropin. PMID- 21015592 TI - Addition of synthetic nutrients to protein supplemental feeds in swine rations. PMID- 21015593 TI - Nutritive requirements of breeding ewes for maintenance, lactation and growth. PMID- 21015594 TI - Heritability of type and condition in range Rambouillet lambs as evaluated by scoring. PMID- 21015595 TI - Heritability of growth and efficiency in beef cattle. PMID- 21015596 TI - A new method for the control of cattle ticks in tropical regions. PMID- 21015597 TI - Ps. pyocyanea; study in vitro and in vivo of the bactericidal and therapeutic properties of alpha-oxyphenazine and a lipoidal product. PMID- 21015598 TI - Effect of feeding green food to the pregnant sow on the incidence of piglet anaemia. PMID- 21015599 TI - A simple technique for the fixation and staining of Trichomonas in cultures and vaginal mucus. PMID- 21015601 TI - Volume changes in the early development of the golden hamster. PMID- 21015600 TI - Neuroanatomical nomenclature and the BNA. PMID- 21015602 TI - A study of the estrous cycle and the breeding of the golden hamster, Cricetus auratus. PMID- 21015603 TI - The effect of facial paralysis on the growth of the skull of rat and rabbit. PMID- 21015604 TI - Effects of chronic administration of diethylstilbestrol on the pituitary and other endocrine organs of hamsters. PMID- 21015605 TI - Growth of lymph nodes, thymus and spleen, and output of thoracic duct lymphocytes in the normal rat. PMID- 21015606 TI - Certain aspects of reproduction in the fur seal. PMID- 21015607 TI - Midbrain regeneration in Amblystoma. PMID- 21015608 TI - Estimation of nuclear population from microtome sections. PMID- 21015609 TI - The study of nephridia and genital ducts since 1895 (continued). PMID- 21015610 TI - A new parasitic cinoflagellate from fresh-water fish. PMID- 21015611 TI - Some Oedogoniaceae and Zygnematceae from Texas and Louisiana. PMID- 21015612 TI - Studies on the trematode family Azygiidae; the morphology and life cycle of Proterometra sagittaria n. sp. PMID- 21015613 TI - Histological and functional studies on the genital tract of Lymnaea stagnalis appressa Say. PMID- 21015614 TI - Six new mites of the super-family Parasitoidea. PMID- 21015615 TI - Zymogen granules in invertebrates. PMID- 21015616 TI - The health and customs of the customs of the Miskito Indians of northern Nicaragua; inter-relationships in a medical program. PMID- 21015617 TI - Yeast genetics; life cycles, cytology, hybridization, vitamin synthesis, and adaptive enzymes. PMID- 21015618 TI - Factors influencing the interaction of insecticidal mists and flying insects; the design of a spray testing chamber and some of its properties. PMID- 21015619 TI - Moonlight and house-haunting habits of female anophelines in West Africa. PMID- 21015620 TI - The influence of certain biological factors on the resistance of bed-bugs (Cimex lectularius, L.) to DDT. PMID- 21015621 TI - [Not Available]. PMID- 21015622 TI - Notes on the subgenus Coquillettidia Dyar (Diptera, Culicidae). PMID- 21015623 TI - A review of 25 years of economic entomology in the Island of Mauritius. PMID- 21015624 TI - The mosquitos of the Kaimosi Forest, Kenya Colony, with special reference to yellow fever. PMID- 21015625 TI - The sandflies of Cyprus (Diptera). PMID- 21015626 TI - Concentration-survival time relationship for roaches injected with arsenicals. PMID- 21015627 TI - Incomplete block experimental designs in insect population problems. PMID- 21015628 TI - Compatibility of cryolite and copper fungicides. PMID- 21015629 TI - A new chlorinated hydrocarbon insecticide. PMID- 21015630 TI - Insect-repellent properties of 2-ethylhexanediol-l, 3. PMID- 21015631 TI - Airplane spraying of rice fields with DDT to kill mosquito larvae. PMID- 21015632 TI - DDT penetration prevented by adding aluminum stearate to DDT-kerosene solutions. PMID- 21015633 TI - Dispersion of DDT sprays from fast combat aircraft. PMID- 21015634 TI - DDT as a larvicide against Simulium. PMID- 21015635 TI - DDT as a chicken louse control. PMID- 21015636 TI - Improved dispenser for testing new liquefied-gas aerosols. PMID- 21015637 TI - Hessian fly infestation in Tennessee and Kentucky. PMID- 21015638 TI - Sabadilla for the control of the green stinkbug. PMID- 21015639 TI - Artificial shelters for measuring densities of Anopheles quadrimaculatus. PMID- 21015640 TI - Occurrence of Pacific Coast Anopheles in brackish water. PMID- 21015641 TI - Factors affecting the larvicidal action of DDT on Culex quinquefasciatus. PMID- 21015642 TI - Internal cork, a new disease of sweet potato of unidentified cause. PMID- 21015643 TI - Effect of storage conditions on survival of Colletotrichum gossypii. PMID- 21015644 TI - The internal infection of cotton seed and the loss of viability in storage. PMID- 21015645 TI - Some factors influencing curly top virus concentration in sugar beets. PMID- 21015646 TI - Mass action as a factor in curly-top-virus infection of sugar beet. PMID- 21015647 TI - Stripe smut (Ustilago striaeformis) in relation to bluegrass improvement. PMID- 21015648 TI - Tatter leaf of sweet cherry. PMID- 21015649 TI - Classification. PMID- 21015650 TI - The mathematical biophysics of some mental phenomena; anxieties and elations. PMID- 21015651 TI - Chain processes and their biophysical applications; the effect of recovery. PMID- 21015652 TI - A contribution to the mathematical biophysics of cell growth and shapes. PMID- 21015653 TI - A theory of membrane permeability; diffusion in the presence of water-flow. PMID- 21015654 TI - The neural mechanism of logical thinking. PMID- 21015655 TI - Studies on the corpus callosum and anterior commissure of monkeys. PMID- 21015656 TI - A comparison of the clinical antimalarial properties and toxicity of several 8 amino quinolines using plasmochin as a standard of references. PMID- 21015657 TI - Riboflavin metabolism after trauma and during convalescence in man. PMID- 21015658 TI - Absence of dinitro-cresol effect in thiouracil-treated rats. PMID- 21015659 TI - Electrical activity of acetylcholine compared with choline, acetate, phosphate, potassium and other substances associated with nerve activity. PMID- 21015660 TI - Electroencephalography of infants under pentothal anesthesia. PMID- 21015661 TI - Study of learning and memory in guinea pigs suffering brain concussion. PMID- 21015662 TI - The origin of the spike potential in nerve. PMID- 21015663 TI - Photolytic lipids from visual pigments. PMID- 21015664 TI - The influence of the pericardium on effective venous pressure. PMID- 21015665 TI - The rate of oxygen consumption in localized regions of the nervous system: in presynaptic endings and in cell bodies. PMID- 21015666 TI - Activity and the development of obesity. PMID- 21015667 TI - The activation of myosin-atpase by pressure in the presence of calcium. PMID- 21015668 TI - The influence of diet on uropepsin elimination. PMID- 21015669 TI - Sodium succinate as an analeptic in man. PMID- 21015670 TI - Number of spermatozoa required for the fertilization of superovulated eggs in the rabbit. PMID- 21015671 TI - Effect of ingestion of food and fluid on tolerance of human subjects to positive acceleration. PMID- 21015672 TI - The effect of environmental temperature upon man's G tolerance. PMID- 21015674 TI - Activation of tissue elements by slow neutron exposure. PMID- 21015673 TI - Plasma renin substrate levels during adrenal insufficiency. PMID- 21015675 TI - Urine volume and phosphorus excretion in human subjects during prolonged exposures to moderately low simulated altitudes. PMID- 21015676 TI - Temporary hearing-loss following exposure to loud tones. PMID- 21015677 TI - The water exchange of diabetes insipidus dogs under varying nutritional and hydration conditions. PMID- 21015678 TI - Relation of B vitamins, inanition and methionine to inactivation of estrone by liver. PMID- 21015679 TI - Studies in nerve degeneration and regeneration. PMID- 21015680 TI - Anticonvulsant action of drugs against metrazol and anti-epileptic activity. PMID- 21015681 TI - The effect of age on the hypoglycemic depletion of glycogen in the central nervous system. PMID- 21015682 TI - Effect of thyroxin on estrogen-induced changes in fowl. PMID- 21015683 TI - The relationship in the hand between total heat exchange and blood flow at various ambient temperatures. PMID- 21015684 TI - Experimental production of uremia in dogs by protein depletion. PMID- 21015685 TI - A practical criterion for evaluating the danger of explosive decompression. PMID- 21015686 TI - Electromyographic observations under conditions of stimulation of the motor cortex. PMID- 21015687 TI - Volume flow of blood through the brain of man at rest, during hyperventilation and while breathing high CO2. PMID- 21015688 TI - Changes in muscle and nerve during prolonged reflex hypertonus and contracture. PMID- 21015689 TI - The measurement of voluntary ventilation capacity. PMID- 21015690 TI - Further observations on the toxic factor in ischemic compression shock. PMID- 21015691 TI - Studies of the central or reflex control of the circulation several years after sympathectomy. PMID- 21015692 TI - The origin of electrical activity from spinal afferent stimulation of the inferior olive of cats. PMID- 21015693 TI - Cause and prevention of a type of leg deformity in brooder raised chicks. PMID- 21015694 TI - Population growth in Puerto Rico and its relation to time changes in vital statistics. PMID- 21015695 TI - The use of inconometrography in graphic exposition; topography and composition of the human body. PMID- 21015696 TI - The relation of country of origin to mortality for various causes in New York State. PMID- 21015697 TI - Hiatus canalis sacralis in American whites and Negroes. PMID- 21015698 TI - General principles of polarographic analysis. PMID- 21015699 TI - Biochemical applications of polarographic analysis. PMID- 21015700 TI - Inorganic applications of polarographic analysis, with special reference to aluminum, magnesium and zinc. PMID- 21015701 TI - Applications of polarographic analysis to the examination of high purity selenium; nickel and cobalt compounds. PMID- 21015702 TI - Polarographic studies; a note on the determination of ascorbic acid. PMID- 21015703 TI - Colour reactions of stilboestrol. PMID- 21015704 TI - The precipitation of tin by tannin. PMID- 21015705 TI - The determination of magnesium in nickel alloys. PMID- 21015706 TI - The colorimetric determination of p-hydroxybenzoic acid and its esters. PMID- 21015707 TI - Biological activity of oxybiotin in the chick. PMID- 21015708 TI - Cobalt metabolism studies; radioactive cobalt procedures with rats and cattle. PMID- 21015709 TI - The protein-formaldehyde reaction; the question of methylene bridges and the unreactivity of benzoyl-d (-)-alanine toward formaldehyde. PMID- 21015710 TI - The effect of estrogens on the succinoxidase system of liver and pituitary tissues. PMID- 21015711 TI - Electron micrographs of crystalline plant viruses. PMID- 21015712 TI - Plant growth under controlled conditions; sucrose content of the tomato plant. PMID- 21015713 TI - The fatty acids of human milk fat. PMID- 21015714 TI - The effect of advancing age on dietary thiamine requirements. PMID- 21015715 TI - Method for the direct determination of diacetyl in tissue and bacterial filtrates. PMID- 21015716 TI - Distribution and general properties of an amylase inhibitor in cereals. PMID- 21015717 TI - Preparation of samples for the microbiological assay of pantothenic acid. PMID- 21015718 TI - The effect of various reagents on adrenocorticotropic hormone. PMID- 21015719 TI - Cocarboxylase as a growth factor for certain strains of Neisseria gonorrhoeae. PMID- 21015720 TI - Oxidation of acetyl phosphate and other substrates by Micrococcus lysodeikticus. PMID- 21015721 TI - Identity of the hydrolytic base obtained from Delphinium brownii Rydb. with lycotonine. PMID- 21015722 TI - The source of acidity of fresh milk from Jersey cows. PMID- 21015723 TI - The effect of solvent and temperature on the viscosity of the polysaccharide or Irish moss and the effect of solvent on its initial gelation. PMID- 21015724 TI - A method of measuring the stabilizing power of extracts of Irish moss. PMID- 21015725 TI - Synthesis of a new alpha-amino acid, S-methyl-betabeta dimethylcysteine. PMID- 21015726 TI - On the specificity of dye titration for ascorbic acid. PMID- 21015727 TI - Isolation of ascorbic acid from rose hips. PMID- 21015728 TI - The synthesis of benzene derivatives structurally similar to penicillic acid. PMID- 21015729 TI - Nitration of starches with nitrogen pentoxide in presence of sodium fluoride. PMID- 21015730 TI - Studies in p-cymene; the saponification rate of isomeric benzoates derived from p cymene. PMID- 21015731 TI - Quinolines; the synthesis of 5- and 7-chloro- and bromo-3-methyl-4 dialkylaminoquinolines. PMID- 21015732 TI - Fundamental studies with the dropping mercury electrode; empirical modification of the Ilkovic equation. PMID- 21015733 TI - Syntheses in the pyrazine series; the preparation and properties of the pyrazyl halides. PMID- 21015734 TI - Osage orange pigments; complete structures of osajin and pomiferin. PMID- 21015735 TI - Curare alkaloids from Chondodendron tomentosum Ruiz and Pavon. PMID- 21015736 TI - Reactions of vanillin and its derived compounds; the reaction of vanillin with silver oxide. PMID- 21015737 TI - An analysis of the streaming potential method of measuring the potential at the interface between solids and liquids. PMID- 21015738 TI - The measurements of the potential at the interface between vitreous silica and pure water. PMID- 21015739 TI - Electrolytic oxidation of lignin. PMID- 21015740 TI - 4-thio and 2,4-dithio 5,5-dialkylthiobarbituric acids. PMID- 21015741 TI - The synthesis of amino acids from ethyl acetamidomalonate and ethyl acetamidocyanoacetate; the use of primary halides. PMID- 21015742 TI - Studies in chemotherapy; antimalarials; halogenated sulfanilamidoheterocycles. PMID- 21015743 TI - Preparation and properties of serum and plasma proteins; a system for the separation into fractions of the protein and lipoprotein components of biological tissues and fluids. PMID- 21015744 TI - Organosilicon compounds; synthesis and properties of n-alkyltrimethyl- and n alkyltriethyl-silanes. PMID- 21015745 TI - Organo-silicon compounds; silicon analogs of neopentyl chloride and neopentyl iodide; the alpha silicon effect. PMID- 21015746 TI - Organo-silicon compounds; alpha- and beta-chloroalkyl silanes and the unusual reactivity of the latter. PMID- 21015747 TI - The reactivity with alkali of chlorine-carbon bonds alpha, beta and gamma to silicon. PMID- 21015748 TI - Antibacterial substances from Asarum canadense; isolation, physical properties and antibacterial action. PMID- 21015749 TI - The higher fatty alcohol esters of gallic acids. PMID- 21015750 TI - Studies on the structure of colchicine. PMID- 21015751 TI - Effect of side reactions on experimental isomerization equilibria. PMID- 21015752 TI - The preparation of n-aryl-alpha-arylaminomaleimides. PMID- 21015753 TI - Metalation of cumene by ethylpotassium. PMID- 21015754 TI - Sodium hydrogen citrates. PMID- 21015755 TI - Studies on the Willgerodt reaction; some extensions of the reaction. PMID- 21015756 TI - Syntheses in the pyrazine series; preparation of 2,5-dicyanopyrazine and the diacetyl diamide of pyrazine dicarboxylic acid-2,5. PMID- 21015757 TI - Polarographic analysis of streptomycin. PMID- 21015758 TI - Effect of hydrocarbon bacteria on racemic mixtures of hydrocarbons. PMID- 21015759 TI - The uronic acid component of heparin. PMID- 21015760 TI - 3-n-pentadecylcatechol. PMID- 21015761 TI - Concerning a proposed modification of the Brunauer-Emmett-Teller theory of multimolecular adsorption. PMID- 21015762 TI - Streptomyces antibiotics; N-methyl-l-glucosamine from streptomycin. PMID- 21015763 TI - New potential chemotherapeutic agents; derivatives of diphenylamine and of alpha alpha-diphenyl-methylamine. PMID- 21015764 TI - The acetone derivatives of hexahydric alcohols; triacetone mannitol and its conversion into d-arabinose. PMID- 21015765 TI - Studies in the detoxication of catalyst poisons; detoxication of carbon disulphide. PMID- 21015766 TI - The constitution of psi-santonin. PMID- 21015767 TI - Experiments in the piperidine series. PMID- 21015768 TI - 1:2:3:4-tetrachloronaphthalene. PMID- 21015769 TI - Ammonia, urea and dental caries. PMID- 21015770 TI - Pregnancy gingivitis. PMID- 21015771 TI - The search for the cause of dental decay; a historical sketch. PMID- 21015772 TI - Orthodontics for the masses. PMID- 21015773 TI - A contribution to the problem of intricate acrylic restorations with special reference to the M.O.D. inlay. PMID- 21015774 TI - Adjustable, non-solid appliance for nasal restoration, attached to upperdenture. PMID- 21015775 TI - Retention of denture in an edentulous cleft palate case. PMID- 21015776 TI - Notes on the dental condition of West African natives. PMID- 21015777 TI - Medico-dental aspects of periodontal disease. PMID- 21015778 TI - Prevention of dental caries. PMID- 21015779 TI - Helpful points in handling children. PMID- 21015781 TI - Cervico-facial orthopaedia. PMID- 21015780 TI - Penicillin in root canal therapy. PMID- 21015782 TI - Notes on glossoptosis and micrognathia. PMID- 21015783 TI - From tooth brushes to spectacles. PMID- 21015784 TI - The problems of dental health. PMID- 21015785 TI - Are dental cripples inevitable? PMID- 21015786 TI - Dental health in children. PMID- 21015787 TI - True acrylic duplication of anteriors for immediate insertion. PMID- 21015788 TI - [Not Available]. PMID- 21015789 TI - [Not Available]. PMID- 21015790 TI - The destructive effect of citrate vs. lactate ions on rats' molar tooth surfaces, in vivo. PMID- 21015791 TI - Use of penicillin as a root canal treatment. PMID- 21015792 TI - The teeth of the Masai. PMID- 21015793 TI - The effect of topical septochem applications on experimental caries. PMID- 21015794 TI - The purpose of the odontoblasts. PMID- 21015795 TI - The formation of secondary dentin and related problems. PMID- 21015796 TI - Nutritional requirements for an oral strain of Lactobacillus acidophilus. PMID- 21015797 TI - Order and age of eruption for the deciduous dentition. PMID- 21015798 TI - Selected phases of complete denture prosthesis; including a discussion of vertical dimension and centric relation. PMID- 21015799 TI - The rational treatment of periodontal disease. PMID- 21015800 TI - Antibiotics in root canal treatment. PMID- 21015801 TI - Xerostomia; discussion and report of a case of psychogenic origin. PMID- 21015802 TI - Localized osteomyelitis. PMID- 21015803 TI - Improve your practice with fluorine therapy. PMID- 21015804 TI - Dentistry in the Veterans Administration. PMID- 21015805 TI - The human elements in denture service. PMID- 21015806 TI - [Not Available]. PMID- 21015807 TI - [Not Available]. PMID- 21015808 TI - [Not Available]. PMID- 21015809 TI - [Not Available]. PMID- 21015810 TI - [Not Available]. PMID- 21015811 TI - [Not Available]. PMID- 21015812 TI - [Not Available]. PMID- 21015813 TI - [Not Available]. PMID- 21015814 TI - [Not Available]. PMID- 21015815 TI - [Not Available]. PMID- 21015816 TI - [Not Available]. PMID- 21015817 TI - [Not Available]. PMID- 21015818 TI - [Not Available]. PMID- 21015819 TI - [Not Available]. PMID- 21015820 TI - [Not Available]. PMID- 21015821 TI - [Not Available]. PMID- 21015822 TI - [Not Available]. PMID- 21015823 TI - [Not Available]. PMID- 21015824 TI - Types of dermatitis in American onchocerciasis. PMID- 21015825 TI - Lemon grass oil; a primary irritant and sensitizing agent. PMID- 21015826 TI - [Not Available]. PMID- 21015827 TI - Erythema streptogenes. PMID- 21015828 TI - Example of need for dermatologic publicity of developments in radiologic physics. PMID- 21015829 TI - Familial benign chronic pemphigus. PMID- 21015830 TI - Fixed sulfathiazole eruption of unusual distribution. PMID- 21015831 TI - Treatment of severe pustular dermatoses and staphylococcic septicemia by oral administration of penicillin. PMID- 21015832 TI - Cheilitis from local use of penicillin solutions in mouth. PMID- 21015833 TI - Urticaria due to trinitrotoluene. PMID- 21015834 TI - A case for diagnosis (fibroma; neurofibroma?). PMID- 21015835 TI - Cavernous hemangioma with ulceration. PMID- 21015836 TI - Hemangioma cavernosum combined with hemangiofibroma tuberosum multiplex associated with probable involvement of the right optic and acoustic nerves. PMID- 21015837 TI - Pustular psoriasis successfully treated with antimony and potassium tartrate. PMID- 21015838 TI - Tinea capitis in a two year old child. PMID- 21015839 TI - Dermatitis medicamentosa (probably due to phenolphthalein). PMID- 21015840 TI - Triple symptom complex of Behcet. PMID- 21015841 TI - A case for diagnosis (tattoo; postinflammatory hyperpigmentation?). PMID- 21015842 TI - A case for diagnosis (hemangioendothelioma; hemangiofibroma?). PMID- 21015843 TI - Lupus erythematosus of the eyelids, chest and neck. PMID- 21015844 TI - Congenital fistula. PMID- 21015845 TI - A case for diagnosis (sarcoid?). PMID- 21015846 TI - Pigmented nevus. PMID- 21015847 TI - Arsenical keratoses disappearing with vitamin A therapy. PMID- 21015848 TI - A case for diagnosis (late syphilis). PMID- 21015849 TI - [Not Available]. PMID- 21015851 TI - Chronic allergic dermatitis. PMID- 21015850 TI - Lupus erythematosus. PMID- 21015852 TI - Bird scabies. PMID- 21015853 TI - Keratosis follicularis in mother and daughter. PMID- 21015854 TI - Perivasculitis. PMID- 21015855 TI - A case for diagnosis (Bazin's disease; multiple thromboses?). PMID- 21015856 TI - Ocular and oral pemphigus. PMID- 21015857 TI - Spiegler-Fendt sarcoid. PMID- 21015858 TI - A case for diagnosis (streptotrichosis; dermatitis factitia?). PMID- 21015859 TI - Dermatomyositis with Raynaud's phenomena. PMID- 21015860 TI - Idiopathic multiple hemorrhagic sarcoma (Kaposi). PMID- 21015861 TI - A case for diagnosis (xeroderma pigmentosum?). PMID- 21015862 TI - Persistent edema of hands and forearms. PMID- 21015863 TI - A case for diagnosis (dermatitis repens?). PMID- 21015864 TI - Poikiloderma vasculare atrophicans. PMID- 21015865 TI - Keratosis palmaris et plantaris (due to arsenic). PMID- 21015866 TI - Tuberous sclerosis. PMID- 21015867 TI - A case for diagnosis (sarcoidosis of the cheeks and forehead; tuberculosis luposa?). PMID- 21015868 TI - Giant cell reticulosis. PMID- 21015869 TI - A case for diagnosis (lymphoma; furunculosis?). PMID- 21015870 TI - Psoriasis. PMID- 21015871 TI - A case for diagnosis (lichen planus?). PMID- 21015872 TI - Acrodermatitis atrophicans chronica. PMID- 21015873 TI - Stomatitis. PMID- 21015874 TI - Lichen planus hypertrophicus. PMID- 21015875 TI - Dermatomyositis. PMID- 21015876 TI - Dermatomyositis. PMID- 21015878 TI - Pityriasis lichenoides et varioliformis acuta (Habermann). PMID- 21015877 TI - Urticaria pigmentosa. PMID- 21015879 TI - Atrophoderma vermiculatum (?). PMID- 21015880 TI - Alopecia areata in twins. PMID- 21015881 TI - Acanthosis nigricans (juvenile type). PMID- 21015882 TI - A case for diagnosis (syphilis?). PMID- 21015883 TI - A case for diagnosis (bullous eruption). PMID- 21015884 TI - Congenital cutaneous atrophy on hands and shins; recent dysphagia. PMID- 21015885 TI - Linear scleroderma. PMID- 21015886 TI - Dermatitis due to nail coating. PMID- 21015887 TI - A case for diagnosis (xeroderma pigmentosum?). PMID- 21015889 TI - Von Recklinghausen's disease in mother, forme fruste type in son and daughter. PMID- 21015888 TI - A case for diagnosis (pemphigus erythematosus limited to the nose?). PMID- 21015890 TI - Dermatitis venenata from rubber gloves. PMID- 21015891 TI - Hemangioma of orbit with cataract. PMID- 21015892 TI - A case for diagnosis (dermatitis herpetiformis; impetigo herpetiformis?). PMID- 21015893 TI - Psoriasis arthropathica. PMID- 21015894 TI - Psoriasis beginning in infancy. PMID- 21015895 TI - Benign pemphigus. PMID- 21015896 TI - A case for diagnosis (erythema multiforme perstans?). PMID- 21015897 TI - Mycosis fungoides (tumor stage). PMID- 21015898 TI - The future of B.P. ointments. PMID- 21015899 TI - Case of patchy punctuate pigmentation for diagnosis. PMID- 21015900 TI - Lichen spinulosus and lichen planus. PMID- 21015901 TI - Epidermolysis bullosa localized to mouth. PMID- 21015902 TI - Folliculitis decalvans, or ulerythema ophryogenes? PMID- 21015903 TI - Cases showing the effects of vitamin C deficiency. PMID- 21015904 TI - A case of lymphocytoma. PMID- 21015905 TI - Meadow grass dermatitis. PMID- 21015906 TI - The Rh factor in blood and related conditions. PMID- 21015907 TI - A review of methods for determining the concentration of penicillin in body fluids. PMID- 21015908 TI - Laboratory aspect of the sulfonamides. PMID- 21015909 TI - The study of the eosinophile in allergic states. PMID- 21015910 TI - The significance of fatty infiltration in the development of hepatic cirrhosis due to choline deficiency. PMID- 21015911 TI - Vitamin C content of market milk, evaporated milk, and powdered whole milk. PMID- 21015912 TI - Studies on the nutritive value of fish proteins; evaluation by the rat growth method and by the Cannon method. PMID- 21015913 TI - Studies on the nutritive value of fish proteins; the use of mackerel protein in the bioassay test for vitamin A. PMID- 21015914 TI - The availability of wheat bran phosphorus for the rat. PMID- 21015915 TI - Relation of fat to economy of food utilization; by the growing albino rat. PMID- 21015916 TI - Relation of fat to economy of food utilization; by the mature albino rat. PMID- 21015917 TI - Vitamin A, ascorbic acid and spinal fluid pressure relationships in the young bovine. PMID- 21015918 TI - The evaluation of proteins in hypoproteinemic dogs. PMID- 21015919 TI - The effect of changes in diet on the volume and composition of rat milk. PMID- 21015920 TI - Carcinogenic value of oxidated oils. PMID- 21015921 TI - Incidence of appendicitis from a survey of college students. PMID- 21015922 TI - Endocrine aspects of obesity. PMID- 21015923 TI - A roentgenologic and gastroscopic study of gastric disease. PMID- 21015924 TI - Gastric endoscopic and secretory findings during salicylism. PMID- 21015925 TI - Tuberculous ulcerative colitis or ulcerative colitis with superimposed tuberculous infection; a case report. PMID- 21015926 TI - Chronic dyspepsia in the Mediterranean Theater. PMID- 21015927 TI - Scleroderma with oesophageal symptoms; a report of two cases. PMID- 21015928 TI - Reticulum cell sarcoma of the stomach. PMID- 21015929 TI - The effect of alumina gel upon the absorption of amino acids, ascorbic acid, glucose, and neutral fat from the intestinal tract. PMID- 21015930 TI - PSYCHOSOMATIC medicine is not new. PMID- 21015931 TI - SYNTHETIC folic acid in macrocytic anemia. PMID- 21015932 TI - THE genetic factor in gastric cancer. PMID- 21015933 TI - The experimental production of exophthalmos in fundulus by means of anterior pituitary extracts. PMID- 21015934 TI - Interruption of ovulation in the hen by subcutaneously administered non-specific substances. PMID- 21015935 TI - The relation between ovulation frequency and the incidence of follicular atresia following surgical operations in the domestic hen. PMID- 21015936 TI - The succinic dehydrogenase activity of ovarian and lutein tissue. PMID- 21015937 TI - The influence of urinary cortin-like material on sodium and potassium metabolism. PMID- 21015938 TI - Relation of carbohydrate deficient diets to the effectiveness of the hormones of the adrenal cortex. PMID- 21015939 TI - Further studies on the chemical nature of compounds which inhibit the function of the thyroid gland. PMID- 21015940 TI - Plasma protein concentrations of rats fed thiourea. PMID- 21015941 TI - Absence of paraxanthine effect on metabolic rate of rats. PMID- 21015942 TI - A study of the toxic, goitrogenic and growth-retarding effects of three derivatives of thiouracil in the albino rat. PMID- 21015943 TI - Alimentary glycosuria in the rat. PMID- 21015944 TI - Constitutionality of compulsory chemical tests to determine alcoholic intoxication. PMID- 21015945 TI - A pair of albino twins. PMID- 21015946 TI - Lysenko's Genetics. PMID- 21015947 TI - Symbols for human pedigree charts. PMID- 21015948 TI - The inheritance of zygodactyly. PMID- 21015949 TI - The multinipple trait in sheep. PMID- 21015950 TI - A mottled-leaf character in winter squash; inherited as a dominant Mendelian character. PMID- 21015952 TI - The snowy belly mouse; a dominant allele of the agouti series in the house mouse. PMID- 21015951 TI - Long husk sterility in maize. PMID- 21015953 TI - [Not Available]. PMID- 21015954 TI - [Not Available]. PMID- 21015955 TI - [Not Available]. PMID- 21015956 TI - [Not Available]. PMID- 21015957 TI - [Not Available]. PMID- 21015958 TI - [Not Available]. PMID- 21015959 TI - [Not Available]. PMID- 21015961 TI - NATIONAL Insurance Bill, 1946. PMID- 21015960 TI - Methods of successful breast feeding. PMID- 21015962 TI - GAS and air analgesia. PMID- 21015963 TI - [Not Available]. PMID- 21015964 TI - [Not Available]. PMID- 21015965 TI - [Not Available]. PMID- 21015966 TI - [Not Available]. PMID- 21015967 TI - [Not Available]. PMID- 21015968 TI - [Not Available]. PMID- 21015969 TI - [Not Available]. PMID- 21015970 TI - [Not Available]. PMID- 21015971 TI - [Not Available]. PMID- 21015972 TI - [Not Available]. PMID- 21015973 TI - [Not Available]. PMID- 21015974 TI - Some newer concepts of the natural derivatives of hemoglobin; general considerations; the serum bilirubin and bilirubinuria; the erythrocyte protoporphyrin. PMID- 21015975 TI - The cardiovascular system in anemia; with a note on the particular abnormalities in sickle cell anemia. PMID- 21015976 TI - Observations on the effect of massive doses of iron given intravenously to patients with hypochromic anemia. PMID- 21015977 TI - Erythroblastosis fetalis in the first-born; prevention of its most severe forms. PMID- 21015978 TI - Relation of contacting surface and anticephalin activity to the maintenance of the fluidity and coagulability of blood. PMID- 21015979 TI - The relation of certain fractions of the plasma globulins to the coagulation defect in hemophilia. PMID- 21015980 TI - [Not Available]. PMID- 21015982 TI - [Not Available]. PMID- 21015981 TI - [Not Available]. PMID- 21015983 TI - [Not Available]. PMID- 21015984 TI - [Not Available]. PMID- 21015985 TI - [Not Available]. PMID- 21015987 TI - [Not Available]. PMID- 21015986 TI - [Not Available]. PMID- 21015988 TI - [Not Available]. PMID- 21015989 TI - Beginning a new year. PMID- 21015990 TI - An essay on the usefulness of medical history for medicine. PMID- 21015991 TI - The jetons of the deans of the old faculty of medicine in Paris. PMID- 21015992 TI - A fourth century A.D. reference to anesthesia. PMID- 21015994 TI - Gastroscopy. PMID- 21015993 TI - Peritoneoscopy. PMID- 21015995 TI - Thoracoscopy. PMID- 21015996 TI - The role of bronchoscopy in diagnosis and treatment. PMID- 21015997 TI - Cystoscopy. PMID- 21015998 TI - ALEUKEMIC LEUKEMIA. PMID- 21015999 TI - Some fragmentary reminiscences of the early history of homeopathy in Michigan. PMID- 21016000 TI - Our tools. PMID- 21016001 TI - A circulating library and index. PMID- 21016002 TI - The Hahnemann Club of Philadelphia. PMID- 21016003 TI - Post-mortem examinations and Jewish law. PMID- 21016004 TI - The hospital and the public. PMID- 21016005 TI - Chinese medicine; ancient and modern. PMID- 21016006 TI - Some problems of a medical records department in a semi-open hospital. PMID- 21016007 TI - Trends in planning; broader service; greater centralization. PMID- 21016008 TI - SMALL hospital; forty beds; expansion to sixty. PMID- 21016009 TI - New wing; function dictates modern layout. PMID- 21016010 TI - Ten steps toward better care for psychiatric patients. PMID- 21016011 TI - Legal hazards of inadequate hospital records. PMID- 21016012 TI - The voluntary hospital looks to the future. PMID- 21016013 TI - Education for administration. PMID- 21016014 TI - An Englishman looks at our mental health service. PMID- 21016015 TI - Progress report on interracial relationships; courtesy privileges for Negro physicians. PMID- 21016016 TI - Conferences at Queen's Hospital prove that department heads have their own ideas. PMID- 21016017 TI - Soft diets made appetizing. PMID- 21016018 TI - A comprehensive mental hygiene program at Caterpillar Tractor Co. PMID- 21016019 TI - Prevention of oral diseases of occupational origin. PMID- 21016020 TI - The relationships between the industrial physician and the community practitioner. PMID- 21016021 TI - The physically impaired worker in industry. PMID- 21016022 TI - INDUSTRIAL medical service for the smaller plants. PMID- 21016023 TI - Industry and medicine; what each expects of the other. PMID- 21016024 TI - Inflammatory phlebostenosis as a factor in the localization of rheumatic diseases. PMID- 21016025 TI - Vision for the job. PMID- 21016026 TI - VENEREAL disease; what stake has industry in its control. PMID- 21016027 TI - Industrial hygiene in New Zealand. PMID- 21016028 TI - An up-to-date factory's medical center. PMID- 21016029 TI - Toxicology of 1,2-dichloropropane (propylene dichloride) studies on effects of daily inhalations. PMID- 21016030 TI - A health survey of pipe covering operations in constructing naval vessels. PMID- 21016031 TI - Exposures to oxides of nitrogen accompanying shrinking operations. PMID- 21016032 TI - An apparatus for rapid sampling of large air volumes for industrial air analyses. PMID- 21016033 TI - Physical capacity for work; principles of industrial physiology and psychology related to the evaluation of the working capacity of the physically impaired. PMID- 21016034 TI - Spontaneous coma due to hypoglycemia in undernourished persons. PMID- 21016035 TI - Group psychotherapy for neuropsychiatric patients being discharged from the Army. PMID- 21016036 TI - Latent neurologic manifestations following decompression; report of a case of severe reaction following ascent to 38,000 feet. PMID- 21016037 TI - Penicillin lozenges in treatment of oral infections. PMID- 21016038 TI - [Not Available]. PMID- 21016039 TI - [Not Available]. PMID- 21016040 TI - The distribution of the various agglutinative types of hemolytic streptococci of group A. PMID- 21016041 TI - Types of streptococci associated with bovine mastitis followed by outbreaks of human disease. PMID- 21016042 TI - Experimental basis of sulfonamide therapy in bacillary dysentery. PMID- 21016043 TI - A study of chemotherapy in experimental bacillary dysentery of Macaca mulatta with emphasis on clearing of the carrier state. PMID- 21016044 TI - Shigella types from eastern France. PMID- 21016045 TI - Studies on the leucocytic picture in brucellosis. PMID- 21016046 TI - Comparative cutaneous tests for filariasis with antigens of different dilutions. PMID- 21016047 TI - Nutritional deficiency and resistance to infection; the effect of biotin deficiency on the susceptibility of rats and mice to infection with Salmonella typhi-murium. PMID- 21016048 TI - Rocky mountain spotted fever; a study of complement fixation in the serum of certain dogs. PMID- 21016049 TI - Production of potent inactivated vaccines with ultra violet irradiation; vaccination against bacillary dysentery. PMID- 21016050 TI - Infection of chick embryos with non-pigmented forms of Plasmodium gallinaceum. PMID- 21016051 TI - Knowlesi malaria in monkeys; microscopic pathological circulatory physiology of rhesus monkeys during acute Plasmodium knowlesi malaria. PMID- 21016052 TI - On the heterologous value of acquired immunity to Plasmodium falciparum. PMID- 21016053 TI - Studies on imported malarias; ability of California anophelines to transmit malarias of foreign origin and other considerations. PMID- 21016054 TI - The use of darkfield illumination in studies of malaria parasites. PMID- 21016055 TI - Description of Chagasia rozeboomi, an anopheline from Ceara, Brazil. PMID- 21016057 TI - [Not Available]. PMID- 21016056 TI - [Not Available]. PMID- 21016058 TI - [Not Available]. PMID- 21016060 TI - [Not Available]. PMID- 21016059 TI - [Not Available]. PMID- 21016061 TI - [Not Available]. PMID- 21016062 TI - [Not Available]. PMID- 21016063 TI - [Not Available]. PMID- 21016065 TI - [Not Available]. PMID- 21016064 TI - [Not Available]. PMID- 21016066 TI - [Not Available]. PMID- 21016067 TI - [Not Available]. PMID- 21016068 TI - [Not Available]. PMID- 21016070 TI - [Not Available]. PMID- 21016069 TI - [Not Available]. PMID- 21016072 TI - [Not Available]. PMID- 21016071 TI - [Not Available]. PMID- 21016073 TI - [Not Available]. PMID- 21016074 TI - [Not Available]. PMID- 21016075 TI - [Not Available]. PMID- 21016076 TI - [Not Available]. PMID- 21016077 TI - [Not Available]. PMID- 21016078 TI - [Not Available]. PMID- 21016079 TI - [Not Available]. PMID- 21016080 TI - [Not Available]. PMID- 21016081 TI - [Not Available]. PMID- 21016082 TI - [Not Available]. PMID- 21016083 TI - [Not Available]. PMID- 21016085 TI - [Not Available]. PMID- 21016084 TI - [Not Available]. PMID- 21016086 TI - [Not Available]. PMID- 21016087 TI - [Not Available]. PMID- 21016088 TI - [Not Available]. PMID- 21016089 TI - [Not Available]. PMID- 21016090 TI - [Not Available]. PMID- 21016091 TI - [Not Available]. PMID- 21016092 TI - [Not Available]. PMID- 21016093 TI - Operative treatment of indirect inguinal hernia. PMID- 21016094 TI - Infantile hepatic cirrhosis. PMID- 21016095 TI - Diagnosis of leprosy. PMID- 21016096 TI - The present day caesarian operation. PMID- 21016097 TI - Impetigo contagiosa. PMID- 21016098 TI - Acute pulmonary oedema. PMID- 21016099 TI - My experience with cinchonine. PMID- 21016101 TI - Toxicosis of mepacrine. PMID- 21016100 TI - Chronic myeloid leukaemia in a girl aged eight years. PMID- 21016102 TI - A case of malaria complicated with meningitis. PMID- 21016103 TI - Cases of diphtheria of tongue. PMID- 21016104 TI - Dynamics of the action of penicillin in experimental animals; observations on mice. PMID- 21016105 TI - Venospasm; its part in producing the clinical picture of Raynaud's disease. PMID- 21016106 TI - Purpuric manifestations of heatstroke; studies of prothrombin and platelets in 12 cases. PMID- 21016107 TI - Chronic cor pulmonale; 60 cases studied at necropsy. PMID- 21016108 TI - Abnormalities in the electrocardiogram following hemolytic streptococcus sore throat. PMID- 21016109 TI - Cytology of the blood and bone marrow of guinea-pigs following haemorrhage, and administration of liver extract. PMID- 21016110 TI - On cruoralbin and its prosthetic group. PMID- 21016112 TI - The role of boron in plant metabolism; the influence of boron on certain enzyme systems. PMID- 21016111 TI - Analysis of sucrose fermentation by yeast at 0 degrees C. with some remarks on selective fermentation. PMID- 21016113 TI - Cystine, methionine and sulphate excretion in cystinuria. PMID- 21016114 TI - The determination of vitamin C by the growth of guinea-pigs. PMID- 21016115 TI - The vitamin C content of dried lucerne (Medicago sativa): chemical and biological assays. PMID- 21016116 TI - The effect of intake of carotene on the general health and on the concentration of carotene and of vitamin A in the blood and liver of sheep. PMID- 21016117 TI - Studies in the metabolism of plant cells; the reversibility of the salt respiration. PMID- 21016118 TI - The quantitative extraction of cobalt and iron from ashed biological material. PMID- 21016119 TI - The effect of cyanide and carbon monoxide on the oxygen consumption of Paramoecium caudatum. PMID- 21016120 TI - [Not Available]. PMID- 21016121 TI - [Not Available]. PMID- 21016122 TI - [Not Available]. PMID- 21016123 TI - [Not Available]. PMID- 21016125 TI - [Not Available]. PMID- 21016124 TI - [Not Available]. PMID- 21016126 TI - [Not Available]. PMID- 21016127 TI - [Not Available]. PMID- 21016128 TI - [Not Available]. PMID- 21016129 TI - [Not Available]. PMID- 21016130 TI - [Not Available]. PMID- 21016131 TI - [Not Available]. PMID- 21016132 TI - [Not Available]. PMID- 21016133 TI - [Not Available]. PMID- 21016134 TI - [Not Available]. PMID- 21016135 TI - [Not Available]. PMID- 21016136 TI - [Not Available]. PMID- 21016137 TI - [Not Available]. PMID- 21016138 TI - [Not Available]. PMID- 21016140 TI - [Not Available]. PMID- 21016139 TI - [Not Available]. PMID- 21016141 TI - [Not Available]. PMID- 21016142 TI - [Not Available]. PMID- 21016143 TI - [Not Available]. PMID- 21016144 TI - [Not Available]. PMID- 21016145 TI - [Not Available]. PMID- 21016146 TI - [Not Available]. PMID- 21016147 TI - [Not Available]. PMID- 21016149 TI - [Not Available]. PMID- 21016148 TI - [Not Available]. PMID- 21016150 TI - [Not Available]. PMID- 21016152 TI - The diagnosis of amoebiasis. PMID- 21016151 TI - [Not Available]. PMID- 21016153 TI - Acroparaesthesia in the lower limbs; unexplained pains in the legs at night. PMID- 21016154 TI - The problems of diphtheria. PMID- 21016155 TI - Prefrontal leucotomy in treatment of post-encephalitic conduct disorder. PMID- 21016156 TI - Penicillin in gonorrhoea; the single-injection method. PMID- 21016157 TI - Ulceration of a foreign body through the small intestine. PMID- 21016158 TI - Traveller's oedema. PMID- 21016159 TI - L.C.C. hospital service; large future developments. PMID- 21016160 TI - Intravenous histamine in the treatment of migraine. PMID- 21016161 TI - Psychiatry in a general hospital. PMID- 21016162 TI - Brucellosis; problems of diagnosis and treatment. PMID- 21016163 TI - The diagnosis of malaria. PMID- 21016164 TI - Rectal bleeding. PMID- 21016165 TI - Early ambulation in surgery. PMID- 21016166 TI - Malpractice suits; the rising tide. PMID- 21016167 TI - Heparin and dicumarol, anticoagulants; their prophylactic and therapeutic uses. PMID- 21016168 TI - Volvulus of the cecum, with left sided colon. PMID- 21016170 TI - A psychiatrist-at-large in Japan. PMID- 21016169 TI - Rupture of the urethra, and impassable stricture of the urethra. PMID- 21016171 TI - Foot strain; a valuable sign. PMID- 21016172 TI - Vincent's angina; some diagnostic pitfalls. PMID- 21016173 TI - The effect of phthalic acid on the prothrombin time of dicumarol-treated dogs. PMID- 21016174 TI - The effects of oxygen on the circulatory system in conditions of anoxia and asphyxia. PMID- 21016175 TI - The effect of inorganic and organic iodides upon the output of respiratory tract fluid. PMID- 21016176 TI - The effect of potassium iodide, sodium iodide, and iodethamine upon the concentration of alcohol-soluble and alcohol-insoluble fractions of blood iodine. PMID- 21016177 TI - Observations on various types of motion causing vomiting in animals. PMID- 21016178 TI - Methods of assaying motion sickness preventives on dogs. PMID- 21016179 TI - A human embryo of two to three pairs of somites. PMID- 21016180 TI - Resistance to extreme temperatures in connection with different diets. PMID- 21016181 TI - The evaluation of diagnostic methods in cardiac disease with special reference to electrocardiography. PMID- 21016182 TI - Is there any advantage in combining several expectorant drugs in a compound cough mixture? PMID- 21016183 TI - Medical practice among the bush Indians of northern Manitoba. PMID- 21016184 TI - Medical survey of nutrition among the northern Manitoba Indians. PMID- 21016185 TI - Clinical aspects of the bowel obstruction problem. PMID- 21016186 TI - Nutritional and environmental studies in south east Asia. PMID- 21016187 TI - Intestinal parasites in the Canadian armed forces. PMID- 21016188 TI - The weak back. PMID- 21016190 TI - Peripheral vascular injuries. PMID- 21016189 TI - Traumatic perforations of tympanic membrane due to blast injury. PMID- 21016191 TI - Localized (pretibial) myxoedema associated with Graves' disease. PMID- 21016192 TI - Metastatic tumours of brain. PMID- 21016193 TI - Echinococcal cyst arising from the prostate. PMID- 21016194 TI - Intussusception in the new born. PMID- 21016195 TI - Boeck's sarcoid. PMID- 21016197 TI - EXAMINATION OF CEREBROSPINAL fluid in syphilis. PMID- 21016196 TI - An unusual case of Meckel's diverticulum. PMID- 21016198 TI - Bronchiectasis. PMID- 21016199 TI - The nutrition of the surgical patient. PMID- 21016200 TI - Routine Rh testing by a simplified conglutination technique. PMID- 21016201 TI - The delivery of medical care. PMID- 21016202 TI - Pediatric aspects of the Salem witchcraft tragedy. PMID- 21016204 TI - PULMONARY complications of thrombophlebitis. PMID- 21016203 TI - Treatment of chronic cervicitis. PMID- 21016205 TI - Plastic repair of facial scars. PMID- 21016206 TI - Opportunities for the private physician in tuberculosis control and treatment. PMID- 21016207 TI - Rheumatic fever; complications and sequelae. PMID- 21016208 TI - [Not Available]. PMID- 21016209 TI - [Not Available]. PMID- 21016210 TI - [Not Available]. PMID- 21016211 TI - Present day conception of protamine zinc insulin and globin insulin with zinc; special references to insulin hypoglycemia and insulin mixtures. PMID- 21016212 TI - Malignant neutropenia; case report with recovery. PMID- 21016213 TI - Penicillin treatment of pneumococcic meningitis. PMID- 21016215 TI - Bacterial warfare. PMID- 21016214 TI - Mutilation of the penis. PMID- 21016216 TI - The seeing eye. PMID- 21016217 TI - Riddle of cancer. PMID- 21016218 TI - Iron saves men. PMID- 21016220 TI - Increasing fertility. PMID- 21016219 TI - The biochemist. PMID- 21016221 TI - Primary optic atrophy in a tabetic African. PMID- 21016223 TI - NOTE on inguinal hernia. PMID- 21016222 TI - Local anaesthesia in abdominal surgery. PMID- 21016224 TI - The construction of Army huts to limit infestation by Ornithodoros moubata (relapsing fever tick). PMID- 21016225 TI - Interstitial emphysema. PMID- 21016226 TI - Clinical picture of scrub typhus in East African troops on the Burma front. PMID- 21016227 TI - The incidence of umbilical herniae in Africans. PMID- 21016228 TI - [Not Available]. PMID- 21016229 TI - The basis of penicillin therapy. PMID- 21016230 TI - The clinical use of penicillin. PMID- 21016231 TI - Penicillin in the treatment of venereal disease; a year's experience in a civilian clinic. PMID- 21016232 TI - Injuries of the cartilage in miners. PMID- 21016233 TI - A new digitalis theory. PMID- 21016234 TI - Intracranial neoplasms produced in dogs by methylcholanthrene. PMID- 21016236 TI - Esophago-cardiogram. PMID- 21016235 TI - Observations on renal tissue aldehydes and their possible role in the mechanism of hypertension. PMID- 21016237 TI - Intrathoracic auscultation in the pneumothorax. PMID- 21016238 TI - Effect of vitamins on sensitivity of striated muscle to acetylcholine and potassium. PMID- 21016239 TI - The action of dysentery toxins on different laboratory animals. PMID- 21016240 TI - The role of potassium and sodium group in biology and medicine. PMID- 21016241 TI - Services rendered by a county health department. PMID- 21016242 TI - CULTURES as an aid in the diagnosis of gonorrhea. PMID- 21016243 TI - Hematology; a round table. PMID- 21016244 TI - Functional nervous disorders. PMID- 21016245 TI - Perianal urticaria. PMID- 21016246 TI - Treatment of the convulsive state at the Illinois Security Hospital. PMID- 21016247 TI - Surface defects of skin; treatment by controlled exfoliation. PMID- 21016248 TI - Tuberculous peritonitis case reports with pathological findings. PMID- 21016249 TI - Experimental blood dyscrasias. PMID- 21016251 TI - Endocrinology in medical practice. PMID- 21016250 TI - Relation of emotion to bodily function. PMID- 21016252 TI - Malpositions of uterus. PMID- 21016253 TI - The therapeutic use of the B vitamins. PMID- 21016254 TI - Muscle re-education in paralysis. PMID- 21016255 TI - Transurethral prostatectomy; with analysis of end results. PMID- 21016256 TI - Chylothorax in a 6 week old infant with recovery. PMID- 21016258 TI - Newer aspects of psychiatry. PMID- 21016257 TI - New developments in the field of allergy. PMID- 21016259 TI - Back abnormalities. PMID- 21016260 TI - Preoperative and postoperative care of biliary tract patients. PMID- 21016261 TI - Malaria in pregnancy; a review of the literature and the presentation of a case. PMID- 21016262 TI - Primary closure and early ambulation in the treatment of the perforated appendix. PMID- 21016263 TI - Further consideration of immunization in childhood. PMID- 21016264 TI - Renal calculus; report of an interesting case. PMID- 21016265 TI - The value of the sedimentation rate test. PMID- 21016266 TI - Infectious hepatitis; a review of 200 cases. PMID- 21016267 TI - Morphologic changes in red blood cell with iron deficiency anemia. PMID- 21016268 TI - Fat and sugar intolerance as cause of gastrointestinal symptoms. PMID- 21016269 TI - Prolonging the effects of penicillin by chilling. PMID- 21016270 TI - Tuberculosis and anal fistula. PMID- 21016271 TI - Diabetic nocturnal diarrhea. PMID- 21016272 TI - Generalized subcutaneous emphysema following resection of large bowel. PMID- 21016273 TI - Visualization of otitic brain abscess with iodized oil. PMID- 21016274 TI - Action of penicillin, especially on Treponema pallidum. PMID- 21016275 TI - Penicillin treatment of the syphilitic pregnant woman. PMID- 21016276 TI - Penicillin in prevention of prenatal syphilis. PMID- 21016277 TI - Penicillin treatment of the syphilitic infant. PMID- 21016278 TI - Treatment of early syphilis with penicillin. PMID- 21016279 TI - Penicillin in the treatment of neurosyphilis. PMID- 21016280 TI - Thrombocytopenic purpura in pregnancy and in the newborn. PMID- 21016281 TI - Privine dependence of two years' duration. PMID- 21016282 TI - Treatment of uremia after acute renal failure by peritoneal irrigation. PMID- 21016283 TI - Cutaneous blastomycosis. PMID- 21016284 TI - Modern concepts of cardiovascular disease. PMID- 21016285 TI - X-ray treatment of sterility resulting from ovarian hypofunction. PMID- 21016287 TI - MEDICINE IN JAPAN. PMID- 21016286 TI - Congenital anomalies following maternal rubella (German measles) during pregnancy. PMID- 21016288 TI - Emboli originating from varicose saphenous thrombophlebitis; report of a case. PMID- 21016289 TI - Adenomyosis. PMID- 21016290 TI - The pre-operative and post-operative uses of gastric suction. PMID- 21016291 TI - The properties and uses of penicillin. PMID- 21016292 TI - Blood examinations. PMID- 21016293 TI - Traumatic shock; hemodynamic effects of alterations of blood viscosity in normal dogs and in dogs in shock. PMID- 21016294 TI - Traumatic shock; the prevention of irreversibility in hemorrhagic shock by viviperfusion of the liver. PMID- 21016295 TI - Hemorrhagic shock; definition and criteria for its diagnosis. PMID- 21016296 TI - Photoelectric study of some factors related to blood clotting. PMID- 21016297 TI - Infectious hepatitis complicated by secondary invasion with Salmonella. PMID- 21016298 TI - On the cause of the respiratory variation of the ballistocardiogram, with a note on sinus arrhythmia. PMID- 21016299 TI - The anemia of infection; hypoferremia, hypercupremia, and alterations in porphyrin metabolism in patients. PMID- 21016301 TI - The absorption into and distribution of penicillin in the cerebrospinal fluid. PMID- 21016300 TI - The anemia of infection; the experimental production of hypoferremia and anemia in dogs. PMID- 21016302 TI - The absorption, distribution, and excretion of streptomycin in man. PMID- 21016303 TI - Bacillus mucosus capsulatus in infantile diarrhea. PMID- 21016304 TI - The effects of active and passive hyperventilation on cerebral blood flow, cerebral oxygen consumption, cardiac output, and blood pressure of normal young men. PMID- 21016305 TI - Hemodynamic changes in salt depletion and in dehydration. PMID- 21016306 TI - The treatment of shock due to salt depletion; comparison of the hemodynamic effects of isotonic saline, of hypertonic saline, and of isotonic glucose solutions. PMID- 21016307 TI - The relationships of oxygen, carbon dioxide, and hemoglobin in the blood of man; oxyhemoglobin dissociation under various physiological conditions. PMID- 21016308 TI - Hepatitis without jaundice in infectious mononucleosis. PMID- 21016309 TI - Western equine encephalomyelitis virus in the blood of experimentally inoculated chickens. PMID- 21016310 TI - St. Louis encephalitis virus in the blood of experimentally inoculated fowls and mammals. PMID- 21016311 TI - Laboratory transmission of Japanese B encephalitis virus by seven species (three genera) of North American mosquitoes. PMID- 21016312 TI - Interference between viruses in tissue culture. PMID- 21016313 TI - Effect of photo-oxidation on isohemagglutinating antibodies. PMID- 21016314 TI - Suppression of growth of Brown-Pearce tumor cells by a specific antibody, with a consideration of the nature of the reacting cell constituent. PMID- 21016315 TI - Period of infectivity of patients with experimentally induced infectious hepatitis. PMID- 21016316 TI - The prostate gland in men over fifty. PMID- 21016317 TI - Treatment of acute cardiac decompensation. PMID- 21016318 TI - [Not Available]. PMID- 21016319 TI - [Not Available]. PMID- 21016320 TI - [Not Available]. PMID- 21016321 TI - [Not Available]. PMID- 21016323 TI - Boeck's sarcoid. PMID- 21016322 TI - [Not Available]. PMID- 21016324 TI - Endocrinology in office practice. PMID- 21016325 TI - Massive arsenotherapy of early syphilis. PMID- 21016326 TI - Deep burns involving bones. PMID- 21016327 TI - Hysterectomy; indications for the various types of operation. PMID- 21016328 TI - Percutaneous tuberculin therapy in behavior disorders of children. PMID- 21016329 TI - Tuberculosis case finding in Marion County high schools. PMID- 21016330 TI - Gamma globulin; availability and indications. PMID- 21016331 TI - Protein requirements of adults. PMID- 21016332 TI - Plasma protein levels in normal individuals. PMID- 21016333 TI - The treatment of bacterial endocarditis with penicillin. PMID- 21016334 TI - Maintenance of therapeutic blood concentrations of penicillin for twenty-four hours following single injections of penicillin-beeswax-peanut oil mixtures. PMID- 21016335 TI - The concentration of penicillin in the spinal fluid following intramuscular administration in neurosyphilis; a negative report. PMID- 21016336 TI - Plague; treatment of experimental animals with streptomycin, sulfadiazine, and sulfapyrazine. PMID- 21016337 TI - The effect of gold chloride on plasma ascorbic acid in the rat. PMID- 21016338 TI - Further studies on the antibacterial action of 3', 5'-dibromosulfanilanilide. PMID- 21016339 TI - The application of the lyophile technique to biologic products; sera, antisera, and antibody globulins. PMID- 21016340 TI - Fundamental information on the mechanism of specific tuberculo-immunity. PMID- 21016341 TI - A rapid test for distinguishing human from cow's milk based upon a difference in their xanthine oxidase content. PMID- 21016342 TI - Modification of the Gutman and Gutman method of estimating acid phosphatase activity. PMID- 21016343 TI - Detection of tubercle bacilli in sputum; application of the NaOH-alum method, the clorox method, and the direct smear. PMID- 21016344 TI - A trap with holder for handling vicious laboratory animals such as wild rats. PMID- 21016345 TI - A laboratory holder for immobilizing experimental rats. PMID- 21016346 TI - A note on the unsuitability of guinea pig jejunum for study by the the Magnus method. PMID- 21016347 TI - Photomicrography; a short method using negative projection prints. PMID- 21016349 TI - Tropical medicine in the war. PMID- 21016348 TI - The management of diabetic acidosis and coma. PMID- 21016350 TI - Bronchoscopy and esophagoscopy in general medicine. PMID- 21016351 TI - Traumatic carotid sinus syndrome followed by idiopathic epilepsy. PMID- 21016352 TI - Cultural examination for Mycobacterium tuberculosis; results in a public health laboratory over a four-year period. PMID- 21016353 TI - Recent progress in planned parenthood. PMID- 21016354 TI - Continuous caudal anesthesia. PMID- 21016355 TI - The Dublin Moro tuberculin test. PMID- 21016356 TI - [Not Available]. PMID- 21016357 TI - [Not Available]. PMID- 21016358 TI - [Not Available]. PMID- 21016359 TI - [Not Available]. PMID- 21016360 TI - [Not Available]. PMID- 21016361 TI - [Not Available]. PMID- 21016362 TI - [Not Available]. PMID- 21016363 TI - [Not Available]. PMID- 21016364 TI - [Not Available]. PMID- 21016365 TI - [Not Available]. PMID- 21016366 TI - [Not Available]. PMID- 21016367 TI - [Not Available]. PMID- 21016368 TI - [Not Available]. PMID- 21016369 TI - [Not Available]. PMID- 21016370 TI - [Not Available]. PMID- 21016371 TI - The use of streptomycin in tularemia. PMID- 21016372 TI - Intrathecal penicillin in treatment of neurosphilis; a preliminary report. PMID- 21016373 TI - Mental hygiene problems of the aged. PMID- 21016374 TI - Modern treatment of peptic ulcer. PMID- 21016375 TI - Early treatment of hay-fever in infancy. PMID- 21016376 TI - The differential diagnosis of sulfa drug reactions. PMID- 21016377 TI - Chemotherapy in management of leukorrheas. PMID- 21016378 TI - Dermatitis venenata of the eyes and eyelids from the local use of penicillin. PMID- 21016379 TI - Hygiene of the anus and rectum. PMID- 21016381 TI - Massive resection of the small intestine. PMID- 21016380 TI - The diagnostic and prognostic signs in cancer of the colon and rectum. PMID- 21016382 TI - Multiple vitamin deficiencies including beriberi heart with congestive failure. PMID- 21016383 TI - Recurrent ulcer resulting from inadequate gastric resection. PMID- 21016384 TI - Proportional dwarfism with delayed sexual maturity; apparent response to desiccated thyroid. PMID- 21016387 TI - In-vivo isosensitisation of red cells in babies with haemolytic disease. PMID- 21016386 TI - Unilateral facial paralysis; correction with tantalum wire; preliminary report on eight cases. PMID- 21016385 TI - Acute infections of pleura treated with and without penicillin. PMID- 21016388 TI - Nicotinamide deficiency precipitated by sulphaguanidine. PMID- 21016389 TI - An epidemic of pneumonia in West Africa. PMID- 21016390 TI - Treatment of syphilis with penicillin. PMID- 21016391 TI - Neurosis and the mental-health service. PMID- 21016392 TI - Nutrition in Newfoundland. PMID- 21016393 TI - [Not Available]. PMID- 21016394 TI - [Not Available]. PMID- 21016395 TI - [Not Available]. PMID- 21016396 TI - [Not Available]. PMID- 21016397 TI - [Not Available]. PMID- 21016398 TI - [Not Available]. PMID- 21016399 TI - [Not Available]. PMID- 21016401 TI - Amoebiasis. PMID- 21016400 TI - A physiologic approach to the blood dyscrasias and their diagnosis. PMID- 21016402 TI - The impact of military surgery on civilian practice. PMID- 21016403 TI - A case of tracheo-oesophageal fistula without oesophageal atresia. PMID- 21016404 TI - TUBERCULOSIS in a general hospital. PMID- 21016405 TI - Hemangioma of the liver. PMID- 21016406 TI - A case of interscapulathoracic amputation for osteogenic sarcoma. PMID- 21016407 TI - [Not Available]. PMID- 21016408 TI - [Not Available]. PMID- 21016410 TI - [Not Available]. PMID- 21016409 TI - [Not Available]. PMID- 21016411 TI - Quinine in malaria. PMID- 21016412 TI - The R.H.Fetherston memorial lecture. PMID- 21016413 TI - An epidemic of poliomyelitis ocurring among troops in the Middle East. PMID- 21016414 TI - A contribution to the problem of masculinization. PMID- 21016415 TI - Purulent meningitis of infancy and childhood: a 12 months' survey of the results of treatment by penicillin. PMID- 21016416 TI - Bilateral trigger thumb in infants. PMID- 21016417 TI - Diaphragmatic hernia. PMID- 21016418 TI - Blood groups in the Maori. PMID- 21016419 TI - The 50th anniversary of the discovery of X-rays. PMID- 21016420 TI - Volvulus of the small bowel, with report of a case treated by resection with recovery. PMID- 21016421 TI - Observations on psychoses occurring in service personnel in forward areas. PMID- 21016422 TI - The adequacy of medical training. PMID- 21016423 TI - Anatomy in the medical curriculum. PMID- 21016424 TI - Plasma protein estimations in battle casualties. PMID- 21016425 TI - Acute suppurative arthritis of the hip. PMID- 21016426 TI - Renal calculus, hydronephrosis and hydroureter. PMID- 21016427 TI - The diagnosis and treatment of fractures of the pelvis. PMID- 21016428 TI - The psychiatric approach to problems of to-day. PMID- 21016429 TI - Reorientation of research. PMID- 21016430 TI - Tonsillectomy; its use and abuse in children. PMID- 21016431 TI - Treatment of neurosyphilis with penicillin. PMID- 21016432 TI - Control of infection in recent wounds by surgery and chemotherapy. PMID- 21016434 TI - Tuberculosis. PMID- 21016433 TI - Two cases of gold poisoning. PMID- 21016435 TI - Primary atypical pneumonia. PMID- 21016436 TI - Observations on dosage of Hall extract. PMID- 21016437 TI - Tuberculosis; the problem of its cure and prevention; what can and should be done if our present methods will never prevent this disease? PMID- 21016438 TI - The task of the practitioner in the tuberculosis problem. PMID- 21016439 TI - The indications for penicillin therapy in some surgical infections. PMID- 21016440 TI - Carcinoma of the stomach. PMID- 21016441 TI - Acute intestinal obstruction in infants and children; physiologic-pathological considerations. PMID- 21016442 TI - Varicose veins. PMID- 21016443 TI - Endometriosis; a case report. PMID- 21016444 TI - Intravenous alimentation in surgical patients. PMID- 21016445 TI - The rehabilitation of patients totally paralyzed below the waist, with special reference to making them ambulatory and capable of earning their own living; control of urination. PMID- 21016446 TI - The intravenous glucose-tolerance test in liver disease. PMID- 21016447 TI - Treatment of fracture of the clavicle by internal nail fixation. PMID- 21016448 TI - The point of view of organized medicine toward the distribution of medical care. PMID- 21016449 TI - Coronary sclerosis with thrombosis; clinicopathological exercises. PMID- 21016450 TI - Cerebral hemangioma, right frontal lobe. PMID- 21016451 TI - Transdiaphragmatic resection of the vagus nerves for peptic ulcer. PMID- 21016452 TI - An interview method for obtaining personal histories. PMID- 21016453 TI - Atropine poisoning; report of a case, with recovery after the ingestion of one gram. PMID- 21016454 TI - Minority views on improving medical care. PMID- 21016455 TI - Media necrosis aortica cystica, with rupture of aortica into pericardium, clinicopathological exercises. PMID- 21016456 TI - Calcareous aortic stenosis; clinicopathological exercises. PMID- 21016457 TI - Medical shock; abnormal biochemical changes in patients with severe, acute medical illnesses, with and without peripheral vascular failure. PMID- 21016458 TI - The early diagnosis of phlebothrombosis. PMID- 21016459 TI - The regional injection of penicillin in local infections; a preliminary report. PMID- 21016460 TI - Practical considerations in the planning and conduct of a national medical-care program. PMID- 21016461 TI - Ewing's sarcoma of first rib. PMID- 21016462 TI - Chronic glomerulonephritis of left kidney; clinicopathological exercises. PMID- 21016464 TI - The results of secondary closure. PMID- 21016463 TI - Peptic ulcer among soldiers in the Mediterranean theater of operations. PMID- 21016465 TI - Medical education and practice in Germany during the war. PMID- 21016466 TI - Carbohydrate metabolism in normal pregnancy. PMID- 21016467 TI - Meckel's diverticulum; with report of a case of intussusception due to its invagination. PMID- 21016468 TI - Syphilis. PMID- 21016469 TI - Pericarditis, adhesive. PMID- 21016470 TI - Adenocarcinoma of rectosigmoid, with perforation. PMID- 21016471 TI - Uterine tumors and urinary obstruction. PMID- 21016472 TI - Studies on the problem of repeated miscarriage; genital hypoplasia. PMID- 21016473 TI - The x-ray and public health; with special reference to tuberculosis. PMID- 21016474 TI - Increased urinary frequency in women caused by extrinsic genitourinary tract lesions. PMID- 21016475 TI - Hodgkin's disease in children. PMID- 21016476 TI - Sclerosing and surgical treatment of varicose veins. PMID- 21016477 TI - Premedication for anesthesia. PMID- 21016478 TI - Treatment of migraine and related headaches. PMID- 21016479 TI - Neostigmine in disorders of the colon. PMID- 21016481 TI - Viceral leishmaniasis. PMID- 21016480 TI - Acute syphilitic nephrosis treated with penicillin. PMID- 21016482 TI - Acute fulminating ulcerative colitis; treatment with streptomycin. PMID- 21016483 TI - Oral penicillin. PMID- 21016484 TI - The group plan of malpractice insurance and defense. PMID- 21016485 TI - The closure of debrided war wounds. PMID- 21016486 TI - Psoriasis; a therapeutic review. PMID- 21016487 TI - Prophylaxis against venereal disease. PMID- 21016488 TI - Meningioma of the cervical spinal dura with postoperative uremia and renal insufficiency. PMID- 21016489 TI - Diseases of the gallbladder and common duct; diagnosis and management. PMID- 21016490 TI - Penicillin in obstetrics; final report. PMID- 21016491 TI - Oral penicillin. PMID- 21016492 TI - Induced sensitivity from the topical use of the sulfonamides and penicillin. PMID- 21016493 TI - Convulsions in infancy and childhood. PMID- 21016494 TI - The determination of permanent disability. PMID- 21016495 TI - The influence of acetylsalicylic acid upon analgesic effect of induced pain. PMID- 21016496 TI - Glossitis and stomatitis due to penicillin lozenges and troches. PMID- 21016497 TI - Myocardial fibrosis in young men; a report of two cases. PMID- 21016498 TI - The present status of the coagulum contact method of skin graft fixation. PMID- 21016499 TI - The surgical management of peripheral vascular disorders. PMID- 21016500 TI - Peripheral arterial diseases. PMID- 21016501 TI - Dental disease and the community. PMID- 21016502 TI - Dental emergencies and the medical practitioner. PMID- 21016503 TI - The significance of dental infections. PMID- 21016504 TI - Modern views on pyorrhoea. PMID- 21016505 TI - The care of the teeth in children. PMID- 21016506 TI - Observations on the elucidation of obscure pyrexia. PMID- 21016507 TI - An investigation of some of the causes of delay in labour. PMID- 21016508 TI - The early recognition of disease; neurological disease. PMID- 21016510 TI - Infant feeding. PMID- 21016509 TI - Treatment of peptic ulcer. PMID- 21016511 TI - TREATMENT of acne. PMID- 21016512 TI - Episiotomy. PMID- 21016513 TI - Physical medicine in the Army; its effect on civil practice. PMID- 21016514 TI - The use of x-rays in the treatment of indurations due to scars and chronic inflammation. PMID- 21016515 TI - Discussion on the clinical implications of the Disabled Persons (Employment) Act, 1944. PMID- 21016516 TI - The Naples typhus epidemic: the use of D.D.T. PMID- 21016517 TI - Neurological experiences in the Middle East and India. PMID- 21016518 TI - An unusual form of epidemic food-poisoning with neurological symptoms. PMID- 21016519 TI - Nutritional disorders of the nervous system in the Middle East. PMID- 21016520 TI - A central nervous deficiency syndrome. PMID- 21016521 TI - Sepsis and asepsis in spinal analgesia. PMID- 21016522 TI - A consideration of uretero-colic union and some experiences in the operation. PMID- 21016523 TI - True aneurysm of left renal artery. PMID- 21016524 TI - Double urethra in a male. PMID- 21016525 TI - Spinal anaesthesia and its effect on a case of hydronephrosis and hydro-ureter. PMID- 21016526 TI - Treatment of slipped upper femoral epiphysis. PMID- 21016527 TI - The value of early movement in the treatment of injuries; fractures. PMID- 21016528 TI - A case of stab wound of the left side of the chest with pneumothorax of the right lung. PMID- 21016529 TI - A case of severe compound fracture of the humerus treated with a vitallium plate. PMID- 21016531 TI - Notes on first aid. PMID- 21016530 TI - A case of head injury and unconsciousness associated with an extraordinary deformity of the spinal column discovered accidentally. PMID- 21016532 TI - BILIARY tract disease. PMID- 21016533 TI - LIVER function tests. PMID- 21016534 TI - [Not Available]. PMID- 21016535 TI - [Not Available]. PMID- 21016536 TI - [Not Available]. PMID- 21016537 TI - [Not Available]. PMID- 21016538 TI - [Not Available]. PMID- 21016539 TI - [Not Available]. PMID- 21016541 TI - [Not Available]. PMID- 21016540 TI - [Not Available]. PMID- 21016542 TI - [Not Available]. PMID- 21016543 TI - [Not Available]. PMID- 21016544 TI - [Not Available]. PMID- 21016545 TI - [Not Available]. PMID- 21016546 TI - [Not Available]. PMID- 21016547 TI - [Not Available]. PMID- 21016548 TI - [Not Available]. PMID- 21016550 TI - [Not Available]. PMID- 21016549 TI - [Not Available]. PMID- 21016551 TI - [Not Available]. PMID- 21016552 TI - [Not Available]. PMID- 21016553 TI - [Not Available]. PMID- 21016554 TI - [Not Available]. PMID- 21016555 TI - [Not Available]. PMID- 21016556 TI - [Not Available]. PMID- 21016557 TI - [Not Available]. PMID- 21016558 TI - [Not Available]. PMID- 21016559 TI - [Not Available]. PMID- 21016560 TI - [Not Available]. PMID- 21016561 TI - [Not Available]. PMID- 21016562 TI - [Not Available]. PMID- 21016563 TI - [Not Available]. PMID- 21016564 TI - [Not Available]. PMID- 21016565 TI - [Not Available]. PMID- 21016566 TI - [Not Available]. PMID- 21016567 TI - [Not Available]. PMID- 21016568 TI - [Not Available]. PMID- 21016569 TI - [Not Available]. PMID- 21016570 TI - [Not Available]. PMID- 21016571 TI - [Not Available]. PMID- 21016572 TI - [Not Available]. PMID- 21016573 TI - [Not Available]. PMID- 21016574 TI - [Not Available]. PMID- 21016575 TI - [Not Available]. PMID- 21016576 TI - [Not Available]. PMID- 21016577 TI - [Not Available]. PMID- 21016578 TI - [Not Available]. PMID- 21016579 TI - [Not Available]. PMID- 21016580 TI - [Not Available]. PMID- 21016581 TI - [Not Available]. PMID- 21016583 TI - [Not Available]. PMID- 21016582 TI - [Not Available]. PMID- 21016584 TI - [Not Available]. PMID- 21016585 TI - [Not Available]. PMID- 21016586 TI - [Not Available]. PMID- 21016587 TI - [Not Available]. PMID- 21016588 TI - [Not Available]. PMID- 21016589 TI - [Not Available]. PMID- 21016590 TI - [Not Available]. PMID- 21016591 TI - [Not Available]. PMID- 21016592 TI - [Not Available]. PMID- 21016593 TI - [Not Available]. PMID- 21016594 TI - [Not Available]. PMID- 21016595 TI - [Not Available]. PMID- 21016596 TI - [Not Available]. PMID- 21016597 TI - [Not Available]. PMID- 21016598 TI - [Not Available]. PMID- 21016599 TI - [Not Available]. PMID- 21016600 TI - [Not Available]. PMID- 21016601 TI - [Not Available]. PMID- 21016602 TI - [Not Available]. PMID- 21016603 TI - [Not Available]. PMID- 21016604 TI - [Not Available]. PMID- 21016605 TI - [Not Available]. PMID- 21016606 TI - [Not Available]. PMID- 21016607 TI - [Not Available]. PMID- 21016609 TI - [Not Available]. PMID- 21016608 TI - [Not Available]. PMID- 21016610 TI - [Not Available]. PMID- 21016611 TI - [Not Available]. PMID- 21016612 TI - [Not Available]. PMID- 21016613 TI - [Not Available]. PMID- 21016614 TI - [Not Available]. PMID- 21016615 TI - [Not Available]. PMID- 21016616 TI - [Not Available]. PMID- 21016617 TI - [Not Available]. PMID- 21016618 TI - [Not Available]. PMID- 21016619 TI - [Not Available]. PMID- 21016620 TI - [Not Available]. PMID- 21016621 TI - [Not Available]. PMID- 21016622 TI - [Not Available]. PMID- 21016624 TI - [Not Available]. PMID- 21016623 TI - [Not Available]. PMID- 21016625 TI - [Not Available]. PMID- 21016626 TI - [Not Available]. PMID- 21016627 TI - [Not Available]. PMID- 21016628 TI - [Not Available]. PMID- 21016629 TI - [Not Available]. PMID- 21016630 TI - [Not Available]. PMID- 21016631 TI - [Not Available]. PMID- 21016632 TI - [Not Available]. PMID- 21016633 TI - [Not Available]. PMID- 21016634 TI - [Not Available]. PMID- 21016635 TI - [Not Available]. PMID- 21016636 TI - [Not Available]. PMID- 21016637 TI - [Not Available]. PMID- 21016638 TI - [Not Available]. PMID- 21016639 TI - [Not Available]. PMID- 21016640 TI - [Not Available]. PMID- 21016642 TI - [Not Available]. PMID- 21016641 TI - [Not Available]. PMID- 21016643 TI - [Not Available]. PMID- 21016644 TI - [Not Available]. PMID- 21016645 TI - [Not Available]. PMID- 21016646 TI - [Not Available]. PMID- 21016647 TI - A doctor looks at the Wagner-Murray-Dingell bill. PMID- 21016648 TI - Sialography. PMID- 21016650 TI - Penicillin nebulization in bronchopulmonary disease; a preliminary report. PMID- 21016649 TI - Delayed suture of wounds associated with fractures. PMID- 21016652 TI - Muscular and some other mechanisms of headache. PMID- 21016651 TI - Esophageal atresia with esophageal-tracheal fistula. PMID- 21016653 TI - Sewage filter flies (Psychoda) as a cause of bronchial asthma; a contribution to the study of insect allergy. PMID- 21016654 TI - The Oxford ether vaporiser. PMID- 21016655 TI - The future of obstetrics. PMID- 21016656 TI - GYNECOLOGICAL significance of nutritional deficiency. PMID- 21016657 TI - THERAPEUTIC use of ascorbic acid. PMID- 21016658 TI - USE of thrombin in skin grafting. PMID- 21016660 TI - PHYSIOLOGY of the adrenal cortex. PMID- 21016659 TI - ANATOMY of the adrenal glands. PMID- 21016661 TI - ORAL penicillin. PMID- 21016662 TI - GELATIN sponge in use. PMID- 21016663 TI - TYROTHRICIN and penicillin. PMID- 21016664 TI - PENICILLIN. PMID- 21016665 TI - [Not Available]. PMID- 21016666 TI - [Not Available]. PMID- 21016667 TI - [Not Available]. PMID- 21016668 TI - [Not Available]. PMID- 21016669 TI - [Not Available]. PMID- 21016670 TI - [Not Available]. PMID- 21016671 TI - [Not Available]. PMID- 21016672 TI - [Not Available]. PMID- 21016673 TI - [Not Available]. PMID- 21016674 TI - [Not Available]. PMID- 21016675 TI - [Not Available]. PMID- 21016676 TI - [Not Available]. PMID- 21016677 TI - [Not Available]. PMID- 21016678 TI - [Not Available]. PMID- 21016679 TI - [Not Available]. PMID- 21016680 TI - [Not Available]. PMID- 21016681 TI - [Not Available]. PMID- 21016682 TI - [Not Available]. PMID- 21016683 TI - [Not Available]. PMID- 21016684 TI - [Not Available]. PMID- 21016685 TI - [Not Available]. PMID- 21016686 TI - [Not Available]. PMID- 21016687 TI - [Not Available]. PMID- 21016688 TI - 17-ketosteroids and adrenal tumors. PMID- 21016689 TI - [Not Available]. PMID- 21016690 TI - [Not Available]. PMID- 21016692 TI - [Not Available]. PMID- 21016691 TI - [Not Available]. PMID- 21016693 TI - Principles underlying the early diagnosis of nutritional deficiency disease. PMID- 21016695 TI - Neurosyphilis with a three year observation of the comparative therapeutic effects of inoculation malaria and artificial fever therapy. PMID- 21016694 TI - The present status of thiouracil in preparing thyrotoxic patients for surgery. PMID- 21016696 TI - The common anemias; incidence, cause and treatment. PMID- 21016697 TI - Chronic subdural hematoma clinical course simulating ruptured intracranial arterial aneurysm; case report. PMID- 21016698 TI - Diaphragmatic hernia; case reports. PMID- 21016699 TI - Colloid (paraphisial) cysts of the third ventricle; report of case with removal and recovery. PMID- 21016700 TI - Hydronephrosis due to aberrant vessels. PMID- 21016701 TI - Psychophysical examination of problem school children. PMID- 21016702 TI - Subpectoral abscess. PMID- 21016703 TI - CATARRHAL jaundice yields to careful investigation. PMID- 21016704 TI - A clinical atlas of sternal bone marrow. PMID- 21016705 TI - Clinical examination of the cerebrospinal fluid; an outline. PMID- 21016706 TI - Laboratory examinations in anemias. PMID- 21016707 TI - Medical experiences in Luzon P.O.W. Camp No. 1. PMID- 21016708 TI - Observations on chancroid therapy with and without sulfathiazole. PMID- 21016709 TI - Common types of low back pain in U.S. Army in the Pacific. PMID- 21016710 TI - Cerebral involvement in schistosomiasis japonicum. PMID- 21016711 TI - 1063 war wounds of the thorax and abdomen. PMID- 21016713 TI - Design of surgical building in use in Pacific theater. PMID- 21016712 TI - Neuropsychiatric case report. PMID- 21016714 TI - Penicillin calcium in oil and beeswax. PMID- 21016715 TI - A new operating table for use in military hospital in forward areas. PMID- 21016716 TI - Local plasma-penicillin therapy in ocular blast injuries. PMID- 21016717 TI - Plastic artificial eye program for middle Pacific area. PMID- 21016718 TI - Treatment of pilonidal cysts at the 249th General Hospital at Clark Field, Luzon, P.I. PMID- 21016719 TI - [Not Available]. PMID- 21016720 TI - [Not Available]. PMID- 21016721 TI - [Not Available]. PMID- 21016722 TI - [Not Available]. PMID- 21016723 TI - [Not Available]. PMID- 21016724 TI - [Not Available]. PMID- 21016725 TI - [Not Available]. PMID- 21016726 TI - [Not Available]. PMID- 21016727 TI - [Not Available]. PMID- 21016728 TI - Amputee rehabilitation; the program; its organization, achievements and future. PMID- 21016729 TI - Statistical analysis of 829 amputations in 769 patients. PMID- 21016730 TI - The open amputation stump; its management, advantages and disadvantages. PMID- 21016731 TI - Problems of revision and reamputation. PMID- 21016732 TI - Plastic and reconstructive surgery of amputation stumps. PMID- 21016733 TI - The role of associated injuries and complications in amputees. PMID- 21016734 TI - Review of 59 patients with multiple amputations. PMID- 21016735 TI - The manufacture of prostheses by naval personnel. PMID- 21016736 TI - Pronation and supination prosthesis for disarticulation about the wrist (rota arm). PMID- 21016737 TI - Production of cosmetic hands and other latex prostheses. PMID- 21016738 TI - Physical rehabilitation of the amputee. PMID- 21016739 TI - Emotional reactions and adjustment of amputees to their injury. PMID- 21016740 TI - Amputee educational rehabilitation and prevocational training. PMID- 21016741 TI - Instruction in automobile driving. PMID- 21016743 TI - The philosophy of and general approach to hearing rehabilitation. PMID- 21016742 TI - Hearing and speech rehabilitation; the history and development of the program. PMID- 21016744 TI - Hearing loss in the Navy and Marine Corps; incidence, etiology, and statistical analysis. PMID- 21016745 TI - Processing aural rehabilitees; coordination of medical and nonmedical services. PMID- 21016746 TI - Physical facilities and equipment for the rehabilitation of hearing. PMID- 21016747 TI - Testing of hearing and fitting of hearing aids. PMID- 21016748 TI - Fabrication of ear molds. PMID- 21016749 TI - Speech reading, auditory training and speech correction in the re-education program. PMID- 21016750 TI - Adjustment of the hard-of-hearing after leaving the service. PMID- 21016751 TI - Rehabilitation of the blinded; traumatic blindness. PMID- 21016752 TI - Nontraumatic blindness. PMID- 21016753 TI - Acrylic eye prostheses. PMID- 21016754 TI - Re-education of the newly blinded. PMID- 21016756 TI - Outside orientation and physical reconditioning. PMID- 21016755 TI - Occupational therapy. PMID- 21016757 TI - Educational and vocational counseling. PMID- 21016758 TI - Neuropsychiatric rehabilitation. PMID- 21016759 TI - The Red Cross in rehabilitation. PMID- 21016760 TI - Planned science or government philanthropy? PMID- 21016761 TI - Ten unmet challenges of public health. PMID- 21016762 TI - The environmental conditions affecting the genetic mechanism of wing production in the chrysanthemum aphid. PMID- 21016763 TI - New amphidiploid species of wheat and their significance for selection and evolution. PMID- 21016764 TI - Curled-blistered wings, a digenic character of Drosophila melanogaster. PMID- 21016765 TI - Occurrence of piebald spotting in a wild house mouse. PMID- 21016766 TI - [Not Available]. PMID- 21016767 TI - [Not Available]. PMID- 21016768 TI - [Not Available]. PMID- 21016769 TI - [Not Available]. PMID- 21016770 TI - Sedimentation and diffusion measurements on glutens from wheats of widely differing quality. PMID- 21016771 TI - [Not Available]. PMID- 21016772 TI - [Not Available]. PMID- 21016773 TI - [Not Available]. PMID- 21016774 TI - [Not Available]. PMID- 21016775 TI - [Not Available]. PMID- 21016776 TI - [Not Available]. PMID- 21016777 TI - [Not Available]. PMID- 21016778 TI - [Not Available]. PMID- 21016779 TI - [Not Available]. PMID- 21016781 TI - [Not Available]. PMID- 21016780 TI - [Not Available]. PMID- 21016782 TI - [Not Available]. PMID- 21016783 TI - [Not Available]. PMID- 21016784 TI - [Not Available]. PMID- 21016786 TI - [Not Available]. PMID- 21016785 TI - [Not Available]. PMID- 21016787 TI - [Not Available]. PMID- 21016788 TI - [Not Available]. PMID- 21016789 TI - [Not Available]. PMID- 21016790 TI - [Not Available]. PMID- 21016791 TI - [Not Available]. PMID- 21016793 TI - [Not Available]. PMID- 21016792 TI - [Not Available]. PMID- 21016794 TI - [Not Available]. PMID- 21016795 TI - [Not Available]. PMID- 21016796 TI - [Not Available]. PMID- 21016797 TI - [Not Available]. PMID- 21016798 TI - [Not Available]. PMID- 21016799 TI - [Not Available]. PMID- 21016800 TI - [Not Available]. PMID- 21016801 TI - [Not Available]. PMID- 21016802 TI - [Not Available]. PMID- 21016803 TI - [Not Available]. PMID- 21016804 TI - [Not Available]. PMID- 21016805 TI - [Not Available]. PMID- 21016806 TI - [Not Available]. PMID- 21016807 TI - [Not Available]. PMID- 21016808 TI - [Not Available]. PMID- 21016809 TI - [Not Available]. PMID- 21016810 TI - [Not Available]. PMID- 21016811 TI - [Not Available]. PMID- 21016812 TI - [Not Available]. PMID- 21016814 TI - [Not Available]. PMID- 21016813 TI - [Not Available]. PMID- 21016815 TI - [Not Available]. PMID- 21016816 TI - [Not Available]. PMID- 21016817 TI - [Not Available]. PMID- 21016818 TI - [Not Available]. PMID- 21016819 TI - [Not Available]. PMID- 21016820 TI - [Not Available]. PMID- 21016821 TI - [Not Available]. PMID- 21016822 TI - [Not Available]. PMID- 21016824 TI - [Not Available]. PMID- 21016823 TI - [Not Available]. PMID- 21016825 TI - [Not Available]. PMID- 21016826 TI - [Not Available]. PMID- 21016827 TI - [Not Available]. PMID- 21016828 TI - [Not Available]. PMID- 21016829 TI - [Not Available]. PMID- 21016830 TI - [Not Available]. PMID- 21016831 TI - [Not Available]. PMID- 21016832 TI - [Not Available]. PMID- 21016833 TI - [Not Available]. PMID- 21016834 TI - [Not Available]. PMID- 21016835 TI - [Not Available]. PMID- 21016836 TI - [Not Available]. PMID- 21016837 TI - [Not Available]. PMID- 21016838 TI - FOOD problem of India. PMID- 21016839 TI - The nucleolus. PMID- 21016840 TI - Techniques in the study of nuclear fission. PMID- 21016841 TI - [Not Available]. PMID- 21016842 TI - [Not Available]. PMID- 21016843 TI - [Not Available]. PMID- 21016844 TI - [Not Available]. PMID- 21016845 TI - [Not Available]. PMID- 21016846 TI - [Not Available]. PMID- 21016847 TI - [Not Available]. PMID- 21016848 TI - [Not Available]. PMID- 21016849 TI - [Not Available]. PMID- 21016850 TI - [Not Available]. PMID- 21016851 TI - [Not Available]. PMID- 21016852 TI - Specification of railroad signal colors and glasses. PMID- 21016853 TI - Attack on refractory clay pots by optical glasses. PMID- 21016854 TI - pH standards at various temperatures; aqueous solutions of acid potassium phthalate. PMID- 21016855 TI - Extraction of alumina from clays and high-silica bauxites. PMID- 21016856 TI - Nuclear energy and its utilization. PMID- 21016857 TI - Synthetic fibres in relation to their competitiveness with cotton. PMID- 21016858 TI - Conversion of ortho- and para-nitro chloro-benzenes to the corresponding anisoles and phenetoles. PMID- 21016859 TI - Biochemical studies in fungi; acid and antibiotic producing capacities of some aspergilli. PMID- 21016860 TI - Biochemical studies in fungi; acid and antibiotic producing capacity of some penicillia. PMID- 21016861 TI - Influence of B-vitamins on the alcohol producing capacity of a strain of distillery yeast. PMID- 21016862 TI - Bibliographia araneorum. PMID- 21016863 TI - Development in the scientific instrument industry in Great Britain. PMID- 21016864 TI - Infective hepatitis in France. PMID- 21016865 TI - Sulphonamides and potato starch refection in the rat. PMID- 21016866 TI - Electron micrography of the virus of influenza. PMID- 21016867 TI - Production of diphtheria toxin by the submerged culture method. PMID- 21016868 TI - Estimation of 1 (+)-arginine in protein hydrolysates by the use of 1 (+)-arginine decarboxylase. PMID- 21016869 TI - Behaviour of the nucleolar olistherozone. PMID- 21016870 TI - Determination of small quantities of phosphorus in steel. PMID- 21016871 TI - Nepalese blood groups. PMID- 21016872 TI - The production of osteomyelitis in rats. PMID- 21016873 TI - A variable path ultrasonic interferometer for the four megacycle region with some measurements on air, CO2, and H2. PMID- 21016874 TI - Experimental arrangement for the measurement of small time intervals between the discharges of Geiger-Muller counters. PMID- 21016876 TI - FALLING ball viscosimeter. PMID- 21016875 TI - Bellows type heat capacity calorimeter. PMID- 21016877 TI - Deposition of calcium phosphates accompanying senile degeneration and disease. PMID- 21016878 TI - A frenching response of tobacco seedlings to isoleucine. PMID- 21016879 TI - On the specificity of epidemic and murine typhus. PMID- 21016880 TI - The target area of mammalian red cells. PMID- 21016881 TI - An instrument for determining the partial pressure of oxygen in a gas. PMID- 21016883 TI - Modification of metabolism apparatus. PMID- 21016882 TI - The use of ultraviolet light in tracing the course of a drug through the body. PMID- 21016884 TI - Malaria and rainfall periodicity in Palestine. PMID- 21016885 TI - Virus encephalomyelitis in buffaloes. PMID- 21016887 TI - Psychiatric problems at Oak Ridge. PMID- 21016886 TI - Incidence of neuropsychiatric disorders in the United States Army in World War II. PMID- 21016888 TI - PSYCHIATRIC testimony before courts-martial. PMID- 21016889 TI - Review of neuropsychiatric cases in the south west Pacific area. PMID- 21016890 TI - Environment; an adjunct in treatment of combat fatigue. PMID- 21016891 TI - Exhaustion syndrome in excited psychotic patients. PMID- 21016892 TI - Desensitization of combat fatigue patients. PMID- 21016893 TI - The study and treatment of alcoholism in the 5th S.C. Rehabilitation Center. PMID- 21016894 TI - Delay (Pavlov) in human physiology; sleepiness on delayed response to stimuli. PMID- 21016895 TI - Convulsive states and coma in cases of islet cell adenoma of the pancreas. PMID- 21016896 TI - Neuropsychiatry at the University of Amsterdam, Holland, 1940-1944. PMID- 21016897 TI - War psychiatry in retrospect. PMID- 21016898 TI - General clinical psychiatry, psychosomatic medicine and psychosurgery. PMID- 21016899 TI - Physiological treatment of psychoses. PMID- 21016900 TI - Alcohol; geriatrics. PMID- 21016901 TI - Neurosyphilis. PMID- 21016902 TI - Child psychiatry; mental deficiency. PMID- 21016903 TI - Heredity and eugenics. PMID- 21016905 TI - Electroencephalography. PMID- 21016904 TI - Epilepsy. PMID- 21016906 TI - Biochemistry, endocrinology and neuropathology. PMID- 21016907 TI - Family care and out-patient mental clinics. PMID- 21016908 TI - Psychiatric social work. PMID- 21016909 TI - Psychiatric nursing. PMID- 21016910 TI - Administrative, forensic and military psychiatry. PMID- 21016911 TI - Psychiatric education. PMID- 21016912 TI - Psychometrics. PMID- 21016913 TI - Histologic changes in the brain in cases of fatal injury to the head; alterations in nerve cells. PMID- 21016914 TI - Disturbances in sleep mechanism; a clinicopathologic study; lesions at the diencephalic level (hypothalamus). PMID- 21016915 TI - Disturbances in sleep mechanism; a clinicopathologic study; lesions at the mesencephalometencephalic level. PMID- 21016916 TI - Studies in diseases of muscle; progressive spinal muscular atrophy as a late sequel of acute epidemic encephalitis; report on two cases. PMID- 21016917 TI - War neuroses. PMID- 21016918 TI - The conditioned reflex treatment of alcoholism. PMID- 21016919 TI - The multiple choice Rorschach test as a differential diagnostic tool. PMID- 21016920 TI - Education, reeducation and psychotherapy. PMID- 21016921 TI - Studies on flying personnel with operational fatigue; studies on dextrose tolerance and electroencephalographic patterns. PMID- 21016922 TI - Camptocormia; a functional condition of the back in neurotic soldiers. PMID- 21016923 TI - Distant secondary circulatory and vasomotor reactions to accidental electric shock. PMID- 21016924 TI - Arnold-Chiari deformity in an adult without obvious cause. PMID- 21016925 TI - Tridione; a new experimental drug for treatment of convulsive and related disorders; pharmacologic aspects. PMID- 21016926 TI - Serous meningitis. PMID- 21016927 TI - Surgical treatment of spontaneous nontraumatic hematoma of the left temporal lobe; report of three cases. PMID- 21016928 TI - The life history of the golden nematode of potatoes, Heterodera rostochiensis Wollenweber, under Long Island, New York, conditions. PMID- 21016929 TI - A new hyphomycete parasitic on a species of nematode. PMID- 21016930 TI - [Not Available]. PMID- 21016931 TI - [Not Available]. PMID- 21016932 TI - [Not Available]. PMID- 21016933 TI - [Not Available]. PMID- 21016935 TI - The pathological condition of the oxidation-reduction systems as a criterion of injury in plants. PMID- 21016934 TI - The redox potentials of fat emulsions under the action of light. PMID- 21016936 TI - Abusive generalizations of the concept of alternation of generations. PMID- 21016937 TI - The role of water in the lethal action of heat on dormant protoplasm. PMID- 21016938 TI - On the origin of anaerobiosis and of endoparasitism in invertebrates. PMID- 21016939 TI - The theoretical aspect of insect metamorphosis. PMID- 21016940 TI - The evolution of the Proboscidea. PMID- 21016941 TI - Bacterial viruses or bacteriophages. PMID- 21016942 TI - The thermal (copper) man, a new instrument for the study of radiation and convection heat loss in man. PMID- 21016943 TI - Comparison of the time concentration curves in arterial blood of dye injected at a constant rate with that of dye injected intravenously. PMID- 21016944 TI - The influence of extrinsic gastro-intestinal innervation on dexedrine induced anorexia. PMID- 21016945 TI - Hypotensive reactions to cross-transfusion in dogs. PMID- 21016946 TI - Response of blood pressure and pulse rate of the new born rat to changes in body temperature. PMID- 21016947 TI - The deterioration of brief endurance work capacity during semi-starvation. PMID- 21016948 TI - The effect of intravenous nitrogen on the respiration and circulation of the cat. PMID- 21016949 TI - Effect of pentothal anesthesia on canine cerebral cortex. PMID- 21016950 TI - The volume and composition of air expelled from the lungs during explosive decompression. PMID- 21016951 TI - Metabolism of dehydroisoandrosterone. PMID- 21016952 TI - Relation of pulmonary ventilation to arterial oxygen saturation. PMID- 21016953 TI - Sexual conditions in Triturus viridescens; the effect of the administration of diethylstilbestrol on adult normal and castrated males. PMID- 21016954 TI - Insulin-induced rumplessness of chickens; experiments with inactivated and reactivated insulin. PMID- 21016955 TI - The production of twins in Gallus domesticus. PMID- 21016956 TI - The developmental relationship between the nervous and epithelial components of the hypophysis. PMID- 21016957 TI - Fertility and hatchability of the prematurely ovulated hen's egg. PMID- 21016958 TI - Mating behavior in male rats castrated at various ages and injected with androgen. PMID- 21016959 TI - [Not Available]. PMID- 21016960 TI - [Not Available]. PMID- 21016961 TI - [Not Available]. PMID- 21016962 TI - [Not Available]. PMID- 21016963 TI - [Not Available]. PMID- 21016964 TI - [Not Available]. PMID- 21016965 TI - [Not Available]. PMID- 21016966 TI - [Not Available]. PMID- 21016967 TI - [Not Available]. PMID- 21016968 TI - [Not Available]. PMID- 21016969 TI - [Not Available]. PMID- 21016970 TI - [Not Available]. PMID- 21016971 TI - [Not Available]. PMID- 21016972 TI - [Not Available]. PMID- 21016973 TI - [Not Available]. PMID- 21016974 TI - [Not Available]. PMID- 21016975 TI - [Not Available]. PMID- 21016976 TI - [Not Available]. PMID- 21016977 TI - [Not Available]. PMID- 21016978 TI - [Not Available]. PMID- 21016979 TI - [Not Available]. PMID- 21016980 TI - [Not Available]. PMID- 21016982 TI - [Not Available]. PMID- 21016981 TI - [Not Available]. PMID- 21016983 TI - [Not Available]. PMID- 21016984 TI - [Not Available]. PMID- 21016985 TI - The mechanism of the Wenckebach type of A-V block. PMID- 21016986 TI - Hypoxaemia tests in coronary disease. PMID- 21016987 TI - Myxoedema with pericardial effusion. PMID- 21016988 TI - Angina pectoris with associated left paroxysmal ptosis. PMID- 21016989 TI - Induced changes in the circulation in constrictive pericarditis. PMID- 21016990 TI - Paravertebral block and the electrocardiogram in angina pectoris. PMID- 21016991 TI - The clinical recognition of coronary artery insufficiency. PMID- 21016992 TI - The Antoine equation for vapor-pressure data. PMID- 21016993 TI - Magnetism and catalysis. PMID- 21016994 TI - The reactions of unsaturated ketones and derivatives with amino compounds; amino ketones. PMID- 21016995 TI - The Ullmann synthesis of biaryls. PMID- 21016996 TI - A discussion of treatment based primarily on labiolingual therapy. PMID- 21016997 TI - Traumatic cyst of the mandible. PMID- 21016998 TI - Localized osteodystrophy of the mandible and maxilla. PMID- 21016999 TI - Conservative management of a large cyst in the mandible. PMID- 21017000 TI - Compound composite odontoma; case report and histologic study. PMID- 21017001 TI - Failure of union in a mandibular fracture and its successful nonsurgical treatment. PMID- 21017002 TI - Decalcification of teeth in cases of achlorhydria. PMID- 21017003 TI - Calcified epithelial cyst in the subcutaneous buccal tissue; case analysis. PMID- 21017004 TI - [Not Available]. PMID- 21017005 TI - [Not Available]. PMID- 21017007 TI - [Not Available]. PMID- 21017006 TI - [Not Available]. PMID- 21017008 TI - [Not Available]. PMID- 21017009 TI - Circumferential wiring; report of a case. PMID- 21017010 TI - A special technique for reduction of the mylohyoid ridge. PMID- 21017011 TI - A critical analysis of the factors in the retention of dentures. PMID- 21017012 TI - Technique for the replacement of broken anterior bridge facings. PMID- 21017014 TI - Planning and designing partial dentures. PMID- 21017013 TI - Treatment of hydrocephalus by prosthesis. PMID- 21017015 TI - Anterior socket collapse technic. PMID- 21017016 TI - Repair of anterior fixed bridge, with an acrylic resin dowel crown. PMID- 21017017 TI - Mechanical technic in root canal therapy. PMID- 21017018 TI - Dentistry in the infantry. PMID- 21017019 TI - LOCAL injection treatment favored in cavity preparation. PMID- 21017020 TI - The need of further information on the incidence of dental caries in primitive peoples. PMID- 21017022 TI - The minimum standard for dental departments in hospitals. PMID- 21017021 TI - Acrylics for dentures. PMID- 21017023 TI - A simplified photographic technique for children. PMID- 21017024 TI - Porcelain jacket crowns. PMID- 21017025 TI - [Not Available]. PMID- 21017026 TI - [Not Available]. PMID- 21017027 TI - [Not Available]. PMID- 21017028 TI - Dental sepsis and mental disorder. PMID- 21017029 TI - Certain psychological and metaphysical factors operative in the practise of dentistry. PMID- 21017030 TI - Periostitis, osteitis and osteomyelitis. PMID- 21017032 TI - The dental assistant's role in oral surgery. PMID- 21017031 TI - Some common causes of failure in dentures. PMID- 21017033 TI - Some recent developments in human feeding. PMID- 21017034 TI - Food plant sanitation is not just a chore. PMID- 21017035 TI - SOYBEAN processing. PMID- 21017036 TI - Trichinae killed by 120-deg. F. dehydration. PMID- 21017037 TI - Gas-packing dry whole milk. PMID- 21017038 TI - How sugars affect dispersibility of pectins in gel powders. PMID- 21017039 TI - RELATIONSHIP between carbohydrate and vitamins shown in case of honey. PMID- 21017040 TI - Aliphatic aldehydes in food flavorings. PMID- 21017041 TI - VITAMINS C and E lead war against food deterioration. PMID- 21017042 TI - [Not Available]. PMID- 21017043 TI - [Not Available]. PMID- 21017044 TI - [Not Available]. PMID- 21017045 TI - The peripheral inhibitory influence of large doses of testosterone on epiphyseal cartilaginous growth. PMID- 21017046 TI - Effect and FSH and LH upon the ovaries of immature chicks and low-producing hens. PMID- 21017047 TI - Biological assay of adrenal corticoids. PMID- 21017048 TI - Histochemical age-changes in normal and pathological placental villi (hydatidiform mole, eclampsia). PMID- 21017049 TI - The relation of the hypophysis to certain changes induced in the rat by the goitrogen, promizole. PMID- 21017050 TI - The influence of hypophysectomy upon plasma iodine and thyroxine content of the thyroid gland of the rat. PMID- 21017052 TI - [Not Available]. PMID- 21017051 TI - Disturbances of water metabolism in vitamin deficiencies and effects of adrenal cortical hormones. PMID- 21017053 TI - [Not Available]. PMID- 21017054 TI - [Not Available]. PMID- 21017055 TI - [Not Available]. PMID- 21017056 TI - [Not Available]. PMID- 21017057 TI - [Not Available]. PMID- 21017058 TI - [Not Available]. PMID- 21017059 TI - [Not Available]. PMID- 21017061 TI - [Not Available]. PMID- 21017060 TI - [Not Available]. PMID- 21017062 TI - [Not Available]. PMID- 21017063 TI - [Not Available]. PMID- 21017064 TI - From the autobiography of a bandit; toward the psychogenesis of so-called psychopathic behavior. PMID- 21017065 TI - Psychiatric clinical service for penology; comments on recent guidance center trends. PMID- 21017066 TI - Accident prevention vs. accident cause. PMID- 21017067 TI - The German National Registration System as means of police control of population. PMID- 21017068 TI - An evaluation of methods for the treatment of urinary incontinence. PMID- 21017069 TI - A general survey of the vaginal smear and its use in research and diagnosis. PMID- 21017070 TI - Premature delivery, causes and results. PMID- 21017071 TI - Ectopic pregnancy; selected data from 110 cases including a report of 2 unusual cases. PMID- 21017072 TI - Puerperal infection; etiologic, prophylactic, and therapeutic considerations. PMID- 21017073 TI - An analysis of the obstetric activities in hospitals of Cook County during 1944. PMID- 21017074 TI - Studies of the origin and treatment of recurrent trichomonas vaginitis. PMID- 21017075 TI - Vinbarbital sodium for obstetric amnesia, analgesia, and anesthesia. PMID- 21017076 TI - Pregnandiol excretion at the onset of labor. PMID- 21017077 TI - Increased excretion of pregnanediol in pregnancy from diethylstilbestrol with special reference to the prevention of late pregnancy accidents. PMID- 21017078 TI - Late complications of the Watkins interposition operation. PMID- 21017079 TI - The fetal mortality in women during the prediabetic period. PMID- 21017080 TI - An unusual decidual reaction in the cervix. PMID- 21017081 TI - Subacute bacterial endocarditis complicated by pregnancy, successfully treated with penicillin. PMID- 21017082 TI - Rupture of the spleen as a complication of pregnancy. PMID- 21017083 TI - [Not Available]. PMID- 21017084 TI - [Not Available]. PMID- 21017085 TI - [Not Available]. PMID- 21017086 TI - [Not Available]. PMID- 21017087 TI - [Not Available]. PMID- 21017088 TI - [Not Available]. PMID- 21017089 TI - [Not Available]. PMID- 21017090 TI - The toxaemias of pregnancy. PMID- 21017091 TI - The obstetrical forceps; controlled axis traction. PMID- 21017092 TI - Correlation of physical and emotional phenomena of natural labour. PMID- 21017093 TI - Intrauterine foetal death due to rhesus incompatibility; its diagnosis and management. PMID- 21017094 TI - A case of intestinal obstruction associated with complete procidentia. PMID- 21017095 TI - The premature baby. PMID- 21017096 TI - [Not Available]. PMID- 21017097 TI - [Not Available]. PMID- 21017098 TI - [Not Available]. PMID- 21017099 TI - [Not Available]. PMID- 21017100 TI - [Not Available]. PMID- 21017101 TI - [Not Available]. PMID- 21017102 TI - [Not Available]. PMID- 21017103 TI - [Not Available]. PMID- 21017104 TI - [Not Available]. PMID- 21017106 TI - [Not Available]. PMID- 21017105 TI - [Not Available]. PMID- 21017107 TI - [Not Available]. PMID- 21017108 TI - [Not Available]. PMID- 21017109 TI - The evolution of histological staining. PMID- 21017110 TI - The staining of fixed tissues. PMID- 21017111 TI - Vital staining. PMID- 21017112 TI - Confiteor. PMID- 21017113 TI - Aristotelian references to the law of reflection. PMID- 21017114 TI - Thomas Walkington and his Optick Glasse. PMID- 21017115 TI - The early development of firearms in China. PMID- 21017116 TI - The education of medical librarians. PMID- 21017117 TI - Bibliography on standards; medical, hospital and nursing libraries and librarians, 1925-1945. PMID- 21017118 TI - The Bacon Library of the American Hospital Association. PMID- 21017119 TI - The Illinois Public Aid Commission and voluntary hospitals. PMID- 21017120 TI - Hospitals and rehabilitation; clinical implications of the Disabled Persons (Employment) Act, 1944. PMID- 21017121 TI - Consents to operations and other surgical procedures; mental deficiency cases and a note on illegal operations. PMID- 21017122 TI - Medical records in the new hospitals. PMID- 21017123 TI - HISTORY'S largest hospital building program launched by VA; General Bradley estimates costs of entire construction at $448,000,000. PMID- 21017124 TI - NATIONAL HOSPITAL Day was born just 25 years ago this month. PMID- 21017126 TI - ADVERTISING Council lends talents to hospital personnel drive. PMID- 21017125 TI - CIVILIAN hospitals take steps to care for 20,000 war veterans. PMID- 21017127 TI - HOW Army hospital problems were met in a previous war. PMID- 21017128 TI - Atmospheric concentrations of fluorides in aluminum reduction plants. PMID- 21017129 TI - A method for the determination of iron in welding fume samples. PMID- 21017130 TI - Nitrogen dioxide; rate of oxidation of nitric oxide and its bearing on the nitrogen dioxide content of electric arc fumes. PMID- 21017132 TI - Lead intoxication by inhalation. PMID- 21017131 TI - Comparison of the chronic toxicity of triethylene glycol with that of diethylene glycol. PMID- 21017134 TI - Chromates in animal nutrition. PMID- 21017133 TI - 2,4-Dinitrophenol poisoning; a case report. PMID- 21017135 TI - The diphtheria situation in Europe. PMID- 21017136 TI - The erythrocyte sedimentation rate. PMID- 21017137 TI - The study of the bacteriology and epidemiology of troop train movements. PMID- 21017139 TI - STREPTOCOCCUS survey, 24 February to 30 March 1945. PMID- 21017138 TI - The relative frequency of respiratory diseases and rheumatic fever at Kearns, Utah. PMID- 21017140 TI - Evaluation of antifibrinolysin plasma levels and antistreptolysin titers in group A streptococcus infections. PMID- 21017141 TI - [Not Available]. PMID- 21017142 TI - [Not Available]. PMID- 21017143 TI - [Not Available]. PMID- 21017144 TI - [Not Available]. PMID- 21017145 TI - [Not Available]. PMID- 21017146 TI - [Not Available]. PMID- 21017147 TI - [Not Available]. PMID- 21017148 TI - [Not Available]. PMID- 21017149 TI - The invasive character of cancer growth. PMID- 21017150 TI - Multiple pulmonary hemangiomata. PMID- 21017151 TI - Effect of streptomycin on experimental brucellosis in guinea pigs. PMID- 21017152 TI - The treatment of acute rheumatic fever with large doses of sodium salicylate; with special reference to dose management and toxic manifestations. PMID- 21017153 TI - Effect of sodium bicarbonate on the therapeutic effectiveness of sulfadiazine in mice. PMID- 21017154 TI - Penicillin in acute nephritis in children. PMID- 21017155 TI - Penicillin therapy in ulcerative colitis. PMID- 21017156 TI - Combined penicillin and sulfadiazine therapy in pneumococcic pneumonia. PMID- 21017157 TI - The influence of sulfanilamide therapy upon the course of acute glomerulonephritis in children. PMID- 21017158 TI - The treatment of temporary renal insufficiency (uremia) by peritoneal lavage. PMID- 21017159 TI - Relative efficiency of quinacrine (atabrine) and quinine in treatment of acute attacks of vivax malaria. PMID- 21017160 TI - Qualitative changes in fibrinogen which influence the erythrocyte sedimentation rate and the clot retraction time. PMID- 21017161 TI - Persistent ventricular bigeminal rhythm in apparently normal hearts. PMID- 21017162 TI - Functional paroxysmal auricular fibrillation. PMID- 21017163 TI - The effect of sodium salicylate on the sedimentation rate of erythrocytes in vivo. PMID- 21017164 TI - Serologic types of bacteria as an epidemiologic principle. PMID- 21017165 TI - The spreading factors and bacterial infection. PMID- 21017166 TI - Absence of antibodies in granulocytes and macrophages during antibody formation. PMID- 21017167 TI - Electrokymography utilizing the fluoroscope. PMID- 21017168 TI - [Not Available]. PMID- 21017169 TI - [Not Available]. PMID- 21017170 TI - [Not Available]. PMID- 21017171 TI - [Not Available]. PMID- 21017172 TI - [Not Available]. PMID- 21017173 TI - [Not Available]. PMID- 21017174 TI - [Not Available]. PMID- 21017175 TI - [Not Available]. PMID- 21017176 TI - [Not Available]. PMID- 21017177 TI - [Not Available]. PMID- 21017178 TI - [Not Available]. PMID- 21017179 TI - [Not Available]. PMID- 21017180 TI - The biological effects of penetrating radiations. PMID- 21017181 TI - Comparative studies of the biological effects of x-rays, neutrons and other ionizing radiations. PMID- 21017182 TI - Genetic effects of radiations. PMID- 21017183 TI - The action of radiations on viruses and bacteria. PMID- 21017184 TI - Quantitative histological analysis of radiation effects in human carcinomata. PMID- 21017185 TI - The measurement of radiation. PMID- 21017187 TI - On technical methods in x-ray therapy. PMID- 21017186 TI - Total energy-absorption in radiotherapy. PMID- 21017188 TI - On technical methods in radium therapy. PMID- 21017189 TI - Protective methods in radiology. PMID- 21017190 TI - The health of India. PMID- 21017191 TI - Causes of delayed menstruation and its treatment. PMID- 21017192 TI - Penicillin sprays and upper respiratory tract infection. PMID- 21017193 TI - Dosage of ephedrine in bronchial asthma and emphysema. PMID- 21017194 TI - Transient non-specific Wassermann and Kahn reactions in a case of infective hepatitis. PMID- 21017195 TI - Successful surgical treatment of enteric group carrier. PMID- 21017196 TI - A case of rapidly cured hysterical paralysis. PMID- 21017197 TI - A plastic splint for opponens pollicis paralysis. PMID- 21017198 TI - Recurrent dislocation of the shoulder. PMID- 21017199 TI - Tubocurarine chloride in anaesthesia. PMID- 21017200 TI - Homosexuality. PMID- 21017201 TI - Penicillin in subacute bacterial endocarditis; report to the Medical Research Council on 147 patients treated in 14 centres appointed by the Penicillin Clinical Trials Committee. PMID- 21017202 TI - Treatment of subacute bacterial endocarditis by penicillin; preliminary report on 18 cases. PMID- 21017203 TI - Sympathectomy in peripheral arteriosclerosis. PMID- 21017204 TI - Primary lung cancer in childhood; report of an unusual case. PMID- 21017205 TI - Survival of cortical bone after bone-grafting. PMID- 21017206 TI - Argentaffin (carcinoid) tumours of the small intestine. PMID- 21017207 TI - Spontaneous rupture of the heart associated with a road accident. PMID- 21017208 TI - Pipette for repeated injections. PMID- 21017209 TI - Social medicine in old age. PMID- 21017210 TI - ISLAM and medicine. PMID- 21017211 TI - PSYCHIATRIC problems of repatriated prisoners. PMID- 21017212 TI - Endotracheal anaesthesia in ear, nose, and throat surgery. PMID- 21017213 TI - The action of thiouracil upon the thyroid gland in Graves' disease. PMID- 21017214 TI - Acute hemorrhagic pancreatitis. PMID- 21017215 TI - A survey on causes and treatment of megacolon. PMID- 21017216 TI - Variations of the sacral canal. PMID- 21017217 TI - A review of pelvic types and their consideration in obstetrics. PMID- 21017218 TI - The history of pictographic human anatomy. PMID- 21017219 TI - Anatomical considerations of the red nucleus. PMID- 21017220 TI - Sphingomyelins; their action on blood cells, particularly lymphocytes; their share in the nucleinate-like action of the ether-insoluble fraction of brain lipoids. PMID- 21017221 TI - Asthma; as observed overseas in a general hospital in the Southwest Pacific area, with special reference to relationship of tropical service to onset and recurrence. PMID- 21017222 TI - The clinical teaching of social medicine. PMID- 21017223 TI - [Not Available]. PMID- 21017224 TI - [Not Available]. PMID- 21017225 TI - [Not Available]. PMID- 21017226 TI - [Not Available]. PMID- 21017227 TI - [Not Available]. PMID- 21017228 TI - [Not Available]. PMID- 21017229 TI - [Not Available]. PMID- 21017230 TI - [Not Available]. PMID- 21017231 TI - [Not Available]. PMID- 21017232 TI - [Not Available]. PMID- 21017233 TI - [Not Available]. PMID- 21017234 TI - [Not Available]. PMID- 21017235 TI - [Not Available]. PMID- 21017236 TI - [Not Available]. PMID- 21017238 TI - Studies in malaria transmission. PMID- 21017237 TI - Social security and national health service for India. PMID- 21017239 TI - Treatment of infantile paralysis in Australia. PMID- 21017240 TI - The present status of penicillin in the therapy of syphilis. PMID- 21017241 TI - Digitalis; a review. PMID- 21017242 TI - The laboratory diagnosis of nutritional disease. PMID- 21017243 TI - Aplastic anaemia following therapeutic administration of stovarsol. PMID- 21017244 TI - Pentothal sodium anaesthesia. PMID- 21017245 TI - Absence of both internal carotid arteries. PMID- 21017246 TI - Blood fractionation products; plasma proteins; properties and uses. PMID- 21017247 TI - Hydatid cyst of the liver. PMID- 21017248 TI - [Not Available]. PMID- 21017249 TI - [Not Available]. PMID- 21017250 TI - [Not Available]. PMID- 21017251 TI - Trichlorethylene anaesthesia. PMID- 21017252 TI - Beriberi in a European. PMID- 21017253 TI - Varicose veins and thrombophlebitis. PMID- 21017254 TI - The treatment of Rhodesian trypanosomiasis with penicillin. PMID- 21017255 TI - The importance of social medicine to Kenya. PMID- 21017256 TI - A report on the treatment of tick relapsing fever with sodium penicillin. PMID- 21017257 TI - The absence of anaemia in hookworm infestation in East African personnel. PMID- 21017258 TI - An unusual stab wound of the abdomen. PMID- 21017259 TI - Malaria in pregnancy. PMID- 21017260 TI - [Not Available]. PMID- 21017261 TI - [Not Available]. PMID- 21017262 TI - [Not Available]. PMID- 21017263 TI - [Not Available]. PMID- 21017264 TI - [Not Available]. PMID- 21017266 TI - [Not Available]. PMID- 21017265 TI - [Not Available]. PMID- 21017267 TI - [Not Available]. PMID- 21017268 TI - Carcinoma of the colon. PMID- 21017269 TI - Rehabilitation after total laryngectomy; successful oesophageal speech. PMID- 21017270 TI - Two cases of sub-acute bacterial endocarditis treated with penicillin. PMID- 21017271 TI - [Not Available]. PMID- 21017272 TI - [Not Available]. PMID- 21017273 TI - [Not Available]. PMID- 21017274 TI - [Not Available]. PMID- 21017275 TI - [Not Available]. PMID- 21017276 TI - [Not Available]. PMID- 21017277 TI - [Not Available]. PMID- 21017278 TI - [Not Available]. PMID- 21017279 TI - [Not Available]. PMID- 21017280 TI - [Not Available]. PMID- 21017281 TI - [Not Available]. PMID- 21017282 TI - [Not Available]. PMID- 21017283 TI - [Not Available]. PMID- 21017285 TI - [Not Available]. PMID- 21017284 TI - [Not Available]. PMID- 21017287 TI - [Not Available]. PMID- 21017286 TI - [Not Available]. PMID- 21017288 TI - [Not Available]. PMID- 21017289 TI - [Not Available]. PMID- 21017290 TI - [Not Available]. PMID- 21017291 TI - [Not Available]. PMID- 21017292 TI - [Not Available]. PMID- 21017293 TI - [Not Available]. PMID- 21017294 TI - [Not Available]. PMID- 21017295 TI - [Not Available]. PMID- 21017296 TI - [Not Available]. PMID- 21017297 TI - [Not Available]. PMID- 21017298 TI - [Not Available]. PMID- 21017299 TI - [Not Available]. PMID- 21017300 TI - [Not Available]. PMID- 21017301 TI - [Not Available]. PMID- 21017302 TI - [Not Available]. PMID- 21017303 TI - [Not Available]. PMID- 21017304 TI - [Not Available]. PMID- 21017305 TI - [Not Available]. PMID- 21017306 TI - [Not Available]. PMID- 21017307 TI - [Not Available]. PMID- 21017308 TI - [Not Available]. PMID- 21017309 TI - [Not Available]. PMID- 21017310 TI - [Not Available]. PMID- 21017311 TI - [Not Available]. PMID- 21017312 TI - The incidence, type and bacteriology of Salmonella infection in the Army in India. PMID- 21017313 TI - Studies in calcium and phosphorus metabolism; the ionic products of calcium phosphates in experimentally induced vitamin D deficiency. PMID- 21017314 TI - Studies on the destruction of vitamin A in shark-liver oil; effect of some anti oxidants on the stabilisation of vitamin A. PMID- 21017315 TI - Vitamin A content of the liver oils of common fresh-water fishes of the Punjab. PMID- 21017317 TI - Investigations on the nutritive value of tapioca (Manihot utilissima). PMID- 21017316 TI - The influence of butter fat in the absence or presence of casein on growth in young rats on a rice diet. PMID- 21017318 TI - An outbreak of lathyrism in central India. PMID- 21017319 TI - Nutrition and dietary surveys in Bijapur District (Bombay Presidency), at the end of the famine year of 1943. PMID- 21017320 TI - Blood urea clearance in Indians. PMID- 21017321 TI - Observations on the physiologically active fraction of Indian hemp, Cannabis sativa Linn. PMID- 21017322 TI - Anaemia in Indian Army recruits. PMID- 21017323 TI - Cultivation of a protozoal parasite of the central nervous system in vitro and its relationship to rabies. PMID- 21017324 TI - A rapid method for the diagnosis of rabies in animals. PMID- 21017325 TI - The susceptibility of Indians to cancer. PMID- 21017326 TI - Paratyphoid C fever. PMID- 21017327 TI - Intracranial herniation syndromes. PMID- 21017328 TI - The stools in clinical sprue. PMID- 21017329 TI - The position of the vermiform appendix. PMID- 21017330 TI - 4:4'Diamidino-diphenyl-ether in the treatment of Indian kala-azar. PMID- 21017331 TI - Sulphanilyl benzamide in the treatment of bacillary dysentery; a preliminary note. PMID- 21017332 TI - Jaundice in amoebic liver abscess; a report of 2 cases. PMID- 21017333 TI - A new technique in sternal puncture. PMID- 21017334 TI - Acute meningitis; some impressions. PMID- 21017335 TI - The treatment of kalaazar with sodium antimony gluconate (stibatin) further observations on the treatment of 32 cases. PMID- 21017336 TI - A case of rhinoscleroma. PMID- 21017337 TI - Sub-types of cholera vibrio isolated from cholera patients in Bombay. PMID- 21017338 TI - The treatment and prevention of vitamin B-1 deficiency in infants; a public health experiment. PMID- 21017339 TI - On the relationship between vitamin B1 and acetyl choline and the action of the latter on the various muscles of the body. PMID- 21017340 TI - Results of treatment of 200 cases of Naga-sore (tropical phagedenic ulcers). PMID- 21017341 TI - Substitution of iodine by sulphonamide in Hobb's glycerine treatment of septic uterus. PMID- 21017342 TI - Principles in the management of external fecal fistulas. PMID- 21017343 TI - Penetration of penicillin into foci of infection. PMID- 21017344 TI - Supradiaphragmatic section of the vagus nerves; effect on gastric secretion and motility in patients with peptic ulcer. PMID- 21017345 TI - Treatment of scarlet fever. PMID- 21017346 TI - An unusual lichenoid dermatosis. PMID- 21017347 TI - Effect of synthetic Lactobacillus casei factor in the treatment of sprue. PMID- 21017348 TI - The effect of atabrine suppressive therapy on eyesight in pilots. PMID- 21017349 TI - Surgical management of acute arterial occlusion. PMID- 21017350 TI - The oral manifestations of iron deficiency. PMID- 21017351 TI - The problem of the dangerous carrier of hemolytic streptococci; the chemtherapeutic control of nasal carriers. PMID- 21017352 TI - Nonoperative treatment of osteomyelitis with penicillin. PMID- 21017353 TI - Surgical treatment of spontaneous nontraumatic hematomas. PMID- 21017354 TI - Desensitization to insect bites. PMID- 21017355 TI - Acute osteomyelitis in a nineteen day old infant. PMID- 21017356 TI - Duodenal bezoar resulting from pica and obstruction of mesentery artery. PMID- 21017357 TI - Types of oedema cases seen in a rural area in Bengal. PMID- 21017358 TI - Infant mortality. PMID- 21017359 TI - Nasal factors in asthma and its treatment. PMID- 21017360 TI - Control of epidemics in U.P. PMID- 21017361 TI - A few results of the application of some new and old forgotten chemotherapeutic principles. PMID- 21017362 TI - Need of sympathetic study of Ayurveda by modern medical men. PMID- 21017363 TI - The British government white paper on a national health service. PMID- 21017364 TI - A fatal case of purpura following sulphapyridine therapy. PMID- 21017365 TI - Kartagener's triad; situs inversus, absent frontal sinuses with maxillary ethmoid and sphenoid infection, and bronchiectasis. PMID- 21017366 TI - The use of curare as an adjuvant for the improvement of muscular relaxation. PMID- 21017367 TI - A comparison of the response of gonorrhea to sulfathiazole and penicillin; analysis of 144 cases. PMID- 21017368 TI - Electroshock convulsion therapy. PMID- 21017369 TI - The sprue syndrome. PMID- 21017370 TI - Aids in the diagnosis of intestinal obstruction. PMID- 21017371 TI - [Not Available]. PMID- 21017372 TI - [Not Available]. PMID- 21017373 TI - [Not Available]. PMID- 21017374 TI - [Not Available]. PMID- 21017375 TI - [Not Available]. PMID- 21017377 TI - Blue nails. PMID- 21017376 TI - Prostatic calculi. PMID- 21017378 TI - MEDICAL education in South Carolina. PMID- 21017379 TI - Surgical convalescence. PMID- 21017380 TI - Professional ethics. PMID- 21017381 TI - Socialized medicine. PMID- 21017383 TI - PROBLEMS of rural medical care. PMID- 21017382 TI - The use of octin in ureterolithiasis, a case report. PMID- 21017384 TI - Cutaneous manifestations of systemic disease. PMID- 21017385 TI - Pre-paid medical care plans. PMID- 21017386 TI - For what type practice should the physician be trained, if general practice what should he be prepared to do? PMID- 21017387 TI - Treatment of acute cardiac emergencies. PMID- 21017388 TI - Health centres and a childhealth service. PMID- 21017389 TI - Acutely infected pleural effusions; techniques of penicillin treatment. PMID- 21017390 TI - Human fertility. PMID- 21017391 TI - Group analysis in a military neurosis centre. PMID- 21017392 TI - Adhesiveness of blood-platelets in haemophilia. PMID- 21017393 TI - Contract dermatitis caused by penicillin. PMID- 21017394 TI - Allergic reaction to parenteral penicillin. PMID- 21017395 TI - A screw-holding screwdriver. PMID- 21017396 TI - Medical observations in Auschwitz concentration camp. PMID- 21017397 TI - MILK-production; the other voice. PMID- 21017398 TI - Future of dentistry. PMID- 21017399 TI - Erysipeloid. PMID- 21017400 TI - Psychiatry and the public-health service. PMID- 21017401 TI - Tissue damage due to cold. PMID- 21017402 TI - Sprain fracture of the carpal scaphoid in children. PMID- 21017403 TI - Acute thyrotoxic myopathy; recovery after partial thyroidectomy. PMID- 21017404 TI - Possible raole of anterior pituitary in human diabetes. PMID- 21017405 TI - Automatic device for ascertaining ventricular enlargement. PMID- 21017406 TI - Cavernous-sinus thrombosis; treated with sulphonamides and penicillin. PMID- 21017408 TI - LIGHTNING injuries. PMID- 21017407 TI - Elimination of gram-negative bacilli from cultures by treatment with other. PMID- 21017409 TI - Family health. PMID- 21017410 TI - IMPORTED smallpox. PMID- 21017411 TI - Penicillin in subacute bacterial endocarditis. PMID- 21017412 TI - Blood-loss in battle casualties; use of transfusion fluids. PMID- 21017413 TI - Urinary mepacrine in relation to incidence and diagnosis of malaria. PMID- 21017414 TI - Spinal anaesthesia; variations in dosage required. PMID- 21017415 TI - Achalasia of oesophagus, following depressed fracture of base of skull. PMID- 21017416 TI - AUTOPSIES for the coroner. PMID- 21017417 TI - Health centres of today; Finsbury, Peckham. PMID- 21017418 TI - [Not Available]. PMID- 21017419 TI - [Not Available]. PMID- 21017420 TI - [Not Available]. PMID- 21017422 TI - [Not Available]. PMID- 21017421 TI - [Not Available]. PMID- 21017423 TI - [Not Available]. PMID- 21017424 TI - [Not Available]. PMID- 21017425 TI - Doctor as seen by the patient. PMID- 21017426 TI - The physiology of atelectasis. PMID- 21017427 TI - The psychosomatic approach in practice. PMID- 21017428 TI - The pathogenesis of amyloidosis. PMID- 21017429 TI - A speculation of nerve impulse mediation. PMID- 21017430 TI - Advances in war medicine and surgery as demonstrated in the European theater of operations. PMID- 21017431 TI - Anesthesia experiences in a marine evacuation hospital on Okinawa. PMID- 21017432 TI - Occupational dermatitis in aircraft workers. PMID- 21017433 TI - Preventive medicine in industry. PMID- 21017434 TI - Vitamins and skin diseases. PMID- 21017435 TI - The use of penicillin in the treatment of war wounds. PMID- 21017436 TI - Treatment of burns; a short review of service burns during the war. PMID- 21017437 TI - Uterine inversion. PMID- 21017438 TI - [Not Available]. PMID- 21017439 TI - [Not Available]. PMID- 21017440 TI - [Not Available]. PMID- 21017442 TI - [Not Available]. PMID- 21017441 TI - [Not Available]. PMID- 21017443 TI - [Not Available]. PMID- 21017444 TI - [Not Available]. PMID- 21017445 TI - A private hospital of less than 40 beds is a poor risk. PMID- 21017446 TI - When is abortion a crime? PMID- 21017447 TI - FEE schedule for medical care of veterans under Servicemen's Readjustment Act, effective in New Jersey, March 1, 1946. PMID- 21017448 TI - [Not Available]. PMID- 21017449 TI - [Not Available]. PMID- 21017450 TI - [Not Available]. PMID- 21017452 TI - [Not Available]. PMID- 21017451 TI - [Not Available]. PMID- 21017453 TI - [Not Available]. PMID- 21017454 TI - [Not Available]. PMID- 21017455 TI - [Not Available]. PMID- 21017456 TI - [Not Available]. PMID- 21017457 TI - [Not Available]. PMID- 21017458 TI - [Not Available]. PMID- 21017459 TI - [Not Available]. PMID- 21017460 TI - [Not Available]. PMID- 21017461 TI - Ascorbic acid in the milk of Melbourne women. PMID- 21017462 TI - Chylangioma of the mesentery, with report of a case, and a brief discussion of mesenteric cysts. PMID- 21017463 TI - The treatment of Haemophilus influenzae meningitis with sulphonamides in conjunction with Haemophilus influenzae, type B, rabbit antiserum. PMID- 21017464 TI - A report on 16 cases of supraglottic oedema. PMID- 21017465 TI - The study of the human body after death. PMID- 21017466 TI - Volkmann's ischaemic contracture of the forearm. PMID- 21017467 TI - Unknown foreign bodies in the lung. PMID- 21017469 TI - RESEARCHES on paludrin (M.4888) in Australia. PMID- 21017468 TI - Tetanus treated with penicillin recovery. PMID- 21017470 TI - The modern treatment of tuberculous empyema. PMID- 21017471 TI - The significance of the blood picture in the diagnosis of anemia in general practice. PMID- 21017472 TI - The last stage of all; hospital care of the aged. PMID- 21017473 TI - The diagnosis and treatment of placenta praevia. PMID- 21017474 TI - Penicillin in the psychoses. PMID- 21017475 TI - Intussusception complicating bacillary dysentery. PMID- 21017476 TI - Arthritic syndromes. PMID- 21017477 TI - Inhalation of carbon dioxide in the treatment of rheumatoid arthritis. PMID- 21017478 TI - The treatment of leg ulcers with pressure bandages. PMID- 21017479 TI - Sitophobia of enteric origin. PMID- 21017480 TI - The genius and his brain. PMID- 21017481 TI - Thinking and problem solving. PMID- 21017482 TI - Influence of estrone, progesterone, and stilbestrol on growth of Lupinus seedlings. PMID- 21017484 TI - Vision. PMID- 21017483 TI - Auscultation over the joints; a new diagnostic method. PMID- 21017485 TI - Urgent maxillofacial surgery. PMID- 21017487 TI - Early ambulation in gynecology and obstetrics. PMID- 21017486 TI - Atypical pneumonia. PMID- 21017488 TI - The problem of the undescended testicle. PMID- 21017489 TI - A suggested regional hospital scheme. PMID- 21017490 TI - Importance of the racial pattern in the practice of medicine in rural areas. PMID- 21017491 TI - Diagnosis and treatment of cerebral arteriosclerosis. PMID- 21017492 TI - The treatment of cardiac asthma. PMID- 21017493 TI - Treatment of carcinoma of the prostate gland. PMID- 21017494 TI - Diagnosis and therapy of peribronchitis. PMID- 21017495 TI - The treatment of acute cholecystitis. PMID- 21017496 TI - Amputations of the lower extremities by means of refrigeration anesthesia. PMID- 21017497 TI - Herewith is outlined a safe rural obstetric service. PMID- 21017498 TI - A discussion of the treatment of varicose veins and ulcers. PMID- 21017499 TI - Stilbestrol administered rectally to reduce nausea results. PMID- 21017500 TI - Inflammation of the nasal sinuses. PMID- 21017501 TI - Carcinoma of the cervix; an attempted follow-up study of 500 cases; the road to improvement in results. PMID- 21017502 TI - Rupture of the ileum in uremia. PMID- 21017503 TI - Herniation of the temporal lobe into the cerebellar fossa. PMID- 21017504 TI - Osteoid sarcoma of the breast; a case report. PMID- 21017505 TI - Resuscitation of the asphyxiated baby delivered by cesarean section. PMID- 21017506 TI - Summarized review of the New Orleans Charity Hospital surgical deaths from July 1, 1943 to July 1, 1944. PMID- 21017507 TI - The present status of the use of tetanus toxoid. PMID- 21017508 TI - The treatment of carcinoma of the larynx. PMID- 21017510 TI - Recent studies on blood coagulation and their clinical applications. PMID- 21017509 TI - Treatment of the cardiac arrhythmias. PMID- 21017511 TI - Obstetrical technique in the home. PMID- 21017512 TI - Beriberi heart disease. PMID- 21017513 TI - Diagnosis of acute porphyria. PMID- 21017514 TI - Death and illness from use of carbon tetrachloride. PMID- 21017515 TI - Geniculate syndrome; case report. PMID- 21017516 TI - Fractures treated by skeletal traction or dual pin fixation; report of 252 cases. PMID- 21017517 TI - The Yakima prepayment plan. PMID- 21017518 TI - PROGRESS in diabetes. PMID- 21017519 TI - PYELONEPHRITIS. PMID- 21017520 TI - HELMINTHIASIS. PMID- 21017522 TI - Asthma: a new conception. PMID- 21017521 TI - PRESENT status of penicillin in syphilis. PMID- 21017523 TI - The surgical management of peripheral vascular disorders; vascular trauma. PMID- 21017524 TI - Anaesthesia for the surgery of peripheral vascular disease. PMID- 21017525 TI - [Not Available]. PMID- 21017526 TI - [Not Available]. PMID- 21017527 TI - [Not Available]. PMID- 21017528 TI - [Not Available]. PMID- 21017529 TI - [Not Available]. PMID- 21017530 TI - [Not Available]. PMID- 21017531 TI - [Not Available]. PMID- 21017532 TI - [Not Available]. PMID- 21017533 TI - [Not Available]. PMID- 21017534 TI - [Not Available]. PMID- 21017536 TI - [Not Available]. PMID- 21017535 TI - [Not Available]. PMID- 21017537 TI - [Not Available]. PMID- 21017538 TI - [Not Available]. PMID- 21017539 TI - [Not Available]. PMID- 21017540 TI - [Not Available]. PMID- 21017541 TI - [Not Available]. PMID- 21017542 TI - [Not Available]. PMID- 21017543 TI - [Not Available]. PMID- 21017544 TI - [Not Available]. PMID- 21017545 TI - [Not Available]. PMID- 21017547 TI - [Not Available]. PMID- 21017546 TI - [Not Available]. PMID- 21017548 TI - [Not Available]. PMID- 21017549 TI - [Not Available]. PMID- 21017550 TI - [Not Available]. PMID- 21017551 TI - [Not Available]. PMID- 21017552 TI - [Not Available]. PMID- 21017553 TI - [Not Available]. PMID- 21017554 TI - [Not Available]. PMID- 21017555 TI - [Not Available]. PMID- 21017556 TI - [Not Available]. PMID- 21017558 TI - [Not Available]. PMID- 21017557 TI - [Not Available]. PMID- 21017559 TI - [Not Available]. PMID- 21017560 TI - [Not Available]. PMID- 21017561 TI - [Not Available]. PMID- 21017562 TI - [Not Available]. PMID- 21017563 TI - [Not Available]. PMID- 21017564 TI - [Not Available]. PMID- 21017565 TI - [Not Available]. PMID- 21017566 TI - [Not Available]. PMID- 21017567 TI - [Not Available]. PMID- 21017568 TI - [Not Available]. PMID- 21017569 TI - [Not Available]. PMID- 21017570 TI - [Not Available]. PMID- 21017571 TI - [Not Available]. PMID- 21017572 TI - [Not Available]. PMID- 21017573 TI - [Not Available]. PMID- 21017574 TI - [Not Available]. PMID- 21017575 TI - [Not Available]. PMID- 21017576 TI - The coagulation of the blood; theoretical and practical aspects. PMID- 21017578 TI - Pulmonary embolism. PMID- 21017577 TI - Management of placenta previa at the Chicago Lying-in Hospital. PMID- 21017580 TI - Congenital aplasia of the ovaries. PMID- 21017579 TI - Physical activity of children with rheumatic heart disease; experience at Sunset Camp. PMID- 21017581 TI - Physical rehabilitation after injury to the spinal cord; report of case with details of procedures. PMID- 21017582 TI - Transurethral resection of the vesical neck in management of cord bladder. PMID- 21017583 TI - Arthrokatadysis; report of case. PMID- 21017584 TI - The measurement of intrapulmonary mixing and pulmonary midcapacity (functional residual air). PMID- 21017585 TI - Sodium salicylate inhibiting anti-Rh immunization in animals. PMID- 21017586 TI - Biochemical changes following poisoning of rats by alphanaphthylthiourea. PMID- 21017587 TI - Modification of anaphylaxis by benadryl. PMID- 21017588 TI - Corneal reaction to viruses of equine encephalomyelitis after intra-ocular injection. PMID- 21017589 TI - A vaccine against Japanese B encephalitis prepared from infected chick embryos. PMID- 21017590 TI - Cytotoxic property of mouse cancer antiserum. PMID- 21017591 TI - Antigenic character of the cancer milk agent in mice. PMID- 21017592 TI - Cell-blockade in canine distemper. PMID- 21017593 TI - Hydroxybenzene compounds as cytoplasmic fixatives. PMID- 21017594 TI - Antipyridoxine activity of 2,4-dimethyl-3-hydroxy-5-hydroxymethylpyridine in the chick. PMID- 21017595 TI - Adrenolytic and sympatholytic actions of priscol (benzyl-imidazoline). PMID- 21017596 TI - Observations on cobalt polycythemia; studies on the peripheral blood of rats. PMID- 21017597 TI - Influence of dimethylaminoethylbenzhydryl ether hydrochloride upon histamine flare reactions. PMID- 21017598 TI - The reputed antipyretic action of camphor. PMID- 21017599 TI - Blood chemical changes following intravenous administration of a case in hydrolysate to human subjects. PMID- 21017600 TI - Is normal human urine toxic? PMID- 21017601 TI - A chick embryo technic for intravenous and chemotherapeutic studies. PMID- 21017602 TI - Effects of electro-convulsive shocks on daily activity of albino rats in revolving drums. PMID- 21017603 TI - Changes in the hydrogen ion concentration of healing fractures. PMID- 21017604 TI - Granulocytopenia in rats given thiourea and thyroxin; the therapeutic effect of L. casei factor. PMID- 21017605 TI - Microbiological determination of amino acids; lysine, histidine, arginine, and valine. PMID- 21017606 TI - The nature of circulating estrogen. PMID- 21017607 TI - Effect of certain amino acids on healing of experimental wounds of the cornea. PMID- 21017608 TI - Accidental air embolism and fibrin formation in the heart of rabbit. PMID- 21017609 TI - Experimental evidence on the cerebral origin of muscle spasticity in acute poliomyelitis. PMID- 21017610 TI - Folic acid therapy in macrocytic anemias of infancy. PMID- 21017611 TI - Effect of acetic, monochloracetic, dichloroacetic, and trichloroacetic acids on oxygen consumption of mouse liver. PMID- 21017612 TI - Electrophoretic analysis of kala-azar human serum; hypergammaglobulinemia associated with seronegative reactions for syphilis. PMID- 21017613 TI - Inactivation of glutamic-aspartic transaminase by irradiation. PMID- 21017614 TI - Biological activity and metabolism of d, 1-0-heterobiotin in the chick. PMID- 21017615 TI - The inactivation of streptomycin and its practical applications. PMID- 21017616 TI - Blood platelets in heterophil anaphylaxis. PMID- 21017617 TI - Subacute and chronic toxicities of ascorbyl palmitates. PMID- 21017618 TI - Use of thermocouples for determination of the rectal temperature of rats. PMID- 21017619 TI - Blood concentration of P-chloro-xylenol in man following parenteral, percutaneous and rectal application. PMID- 21017620 TI - [Not Available]. PMID- 21017621 TI - [Not Available]. PMID- 21017622 TI - [Not Available]. PMID- 21017623 TI - [Not Available]. PMID- 21017624 TI - [Not Available]. PMID- 21017625 TI - [Not Available]. PMID- 21017626 TI - [Not Available]. PMID- 21017627 TI - [Not Available]. PMID- 21017628 TI - [Not Available]. PMID- 21017629 TI - [Not Available]. PMID- 21017630 TI - [Not Available]. PMID- 21017631 TI - [Not Available]. PMID- 21017632 TI - [Not Available]. PMID- 21017633 TI - [Not Available]. PMID- 21017634 TI - [Not Available]. PMID- 21017635 TI - [Not Available]. PMID- 21017636 TI - [Not Available]. PMID- 21017637 TI - [Not Available]. PMID- 21017638 TI - [Not Available]. PMID- 21017639 TI - [Not Available]. PMID- 21017640 TI - [Not Available]. PMID- 21017641 TI - [Not Available]. PMID- 21017642 TI - [Not Available]. PMID- 21017643 TI - [Not Available]. PMID- 21017644 TI - [Not Available]. PMID- 21017645 TI - [Not Available]. PMID- 21017646 TI - [Not Available]. PMID- 21017647 TI - [Not Available]. PMID- 21017648 TI - [Not Available]. PMID- 21017649 TI - [Not Available]. PMID- 21017650 TI - [Not Available]. PMID- 21017651 TI - [Not Available]. PMID- 21017652 TI - [Not Available]. PMID- 21017653 TI - [Not Available]. PMID- 21017654 TI - [Not Available]. PMID- 21017655 TI - [Not Available]. PMID- 21017656 TI - [Not Available]. PMID- 21017657 TI - [Not Available]. PMID- 21017658 TI - [Not Available]. PMID- 21017659 TI - [Not Available]. PMID- 21017660 TI - [Not Available]. PMID- 21017661 TI - The surgery of the veins of the legs; varicosity and some problems in thrombosis. PMID- 21017662 TI - Internal derangements of the knee-joint; the x-ray diagnosis. PMID- 21017663 TI - A discussion of the causes of cancer. PMID- 21017664 TI - Paying for medical care under the Rhode Island Public Assistance Act. PMID- 21017665 TI - The plan for a voluntary surgical insurance program for Rhode Island. PMID- 21017666 TI - The injection treatment of hemorrhoids. PMID- 21017667 TI - Medical care for the veterans. PMID- 21017668 TI - Opinion poll of physicians regarding neuropsychiatric conditions among World War II veterans in Rhode Island. PMID- 21017669 TI - Streptomycin. PMID- 21017670 TI - Some experiences in psychiatry and surgery with 102nd General Hospital, Bari, Italy. PMID- 21017671 TI - Electroencephalography in mental hospital practice. PMID- 21017672 TI - PREDECESSORS of penicillin. PMID- 21017673 TI - A pure Vi strain of Bact. typhosum. PMID- 21017674 TI - Should sterilisation be legalised? PMID- 21017675 TI - A note on the sulphonamide drugs as inhibitors of intestinal vitamin synthesis in man. PMID- 21017676 TI - [Not Available]. PMID- 21017677 TI - [Not Available]. PMID- 21017678 TI - [Not Available]. PMID- 21017679 TI - [Not Available]. PMID- 21017680 TI - [Not Available]. PMID- 21017681 TI - [Not Available]. PMID- 21017683 TI - [Not Available]. PMID- 21017682 TI - [Not Available]. PMID- 21017684 TI - [Not Available]. PMID- 21017685 TI - [Not Available]. PMID- 21017686 TI - [Not Available]. PMID- 21017687 TI - [Not Available]. PMID- 21017688 TI - [Not Available]. PMID- 21017689 TI - [Not Available]. PMID- 21017690 TI - [Not Available]. PMID- 21017691 TI - [Not Available]. PMID- 21017692 TI - [Not Available]. PMID- 21017693 TI - The ophthalmologist and extraocular conditions. PMID- 21017694 TI - [Not Available]. PMID- 21017695 TI - [Not Available]. PMID- 21017696 TI - [Not Available]. PMID- 21017697 TI - [Not Available]. PMID- 21017698 TI - [Not Available]. PMID- 21017699 TI - [Not Available]. PMID- 21017700 TI - [Not Available]. PMID- 21017701 TI - [Not Available]. PMID- 21017702 TI - [Not Available]. PMID- 21017703 TI - [Not Available]. PMID- 21017704 TI - [Not Available]. PMID- 21017705 TI - [Not Available]. PMID- 21017707 TI - [Not Available]. PMID- 21017706 TI - [Not Available]. PMID- 21017708 TI - [Not Available]. PMID- 21017709 TI - [Not Available]. PMID- 21017710 TI - [Not Available]. PMID- 21017711 TI - [Not Available]. PMID- 21017712 TI - [Not Available]. PMID- 21017713 TI - [Not Available]. PMID- 21017714 TI - [Not Available]. PMID- 21017715 TI - [Not Available]. PMID- 21017716 TI - [Not Available]. PMID- 21017718 TI - [Not Available]. PMID- 21017717 TI - [Not Available]. PMID- 21017719 TI - [Not Available]. PMID- 21017720 TI - [Not Available]. PMID- 21017721 TI - Carcinoid tumor of rectum. PMID- 21017722 TI - Adenomatous polyp of the rectum in a child. PMID- 21017723 TI - Papillary cystoadenoma of the tongue. PMID- 21017724 TI - Carcinoma (cylindroma) of parotid salivary gland. PMID- 21017725 TI - Theca cell tumor of the ovary with masculinization in a pregnant woman. PMID- 21017726 TI - Chorionepithelioma of the uterus developing from a hydatidiform mole. PMID- 21017727 TI - Embryonal cell carcinoma of sacral region. PMID- 21017728 TI - Granular cell myoblastoma of lumbar region. PMID- 21017729 TI - Leiomyosarcoma of retroperitoneal tissues. PMID- 21017730 TI - Eosinophilic granuloma of spine of lumbar vertebra. PMID- 21017731 TI - Plasma cell myeloma (bilateral) of tibia. PMID- 21017732 TI - [Not Available]. PMID- 21017733 TI - [Not Available]. PMID- 21017734 TI - [Not Available]. PMID- 21017735 TI - [Not Available]. PMID- 21017736 TI - [Not Available]. PMID- 21017737 TI - [Not Available]. PMID- 21017738 TI - [Not Available]. PMID- 21017739 TI - [Not Available]. PMID- 21017740 TI - [Not Available]. PMID- 21017741 TI - [Not Available]. PMID- 21017742 TI - [Not Available]. PMID- 21017743 TI - [Not Available]. PMID- 21017744 TI - [Not Available]. PMID- 21017745 TI - [Not Available]. PMID- 21017746 TI - [Not Available]. PMID- 21017747 TI - [Not Available]. PMID- 21017748 TI - [Not Available]. PMID- 21017749 TI - [Not Available]. PMID- 21017750 TI - [Not Available]. PMID- 21017752 TI - [Not Available]. PMID- 21017753 TI - [Not Available]. PMID- 21017751 TI - [Not Available]. PMID- 21017754 TI - [Not Available]. PMID- 21017755 TI - [Not Available]. PMID- 21017756 TI - [Not Available]. PMID- 21017757 TI - [Not Available]. PMID- 21017758 TI - Blood needs of the wounded. PMID- 21017759 TI - Hepatitis. PMID- 21017761 TI - Compound injuries of the knee joint. PMID- 21017760 TI - The management of war wounds of the chest; a summary. PMID- 21017762 TI - Secondary closure of war wounds with early healing and return to duty. PMID- 21017763 TI - The management of battle fractures. PMID- 21017764 TI - Brain and nerve injuries. PMID- 21017765 TI - DETECTION of virulent diphtheria bacilli. PMID- 21017766 TI - U.S. Army diet. PMID- 21017767 TI - BRACE for flexor paralysis at the elbow. PMID- 21017768 TI - SUBSTAGE slide marker. PMID- 21017769 TI - INCIDENCE of somatization reactions in psychoneurotic disorders. PMID- 21017770 TI - Colon injuries in amphibious warfare. PMID- 21017771 TI - Arthroplasty of the elbow. PMID- 21017772 TI - Pellagra in Americans in a Japanese prison. PMID- 21017773 TI - The battle neurosis. PMID- 21017774 TI - Topical penicillin treatment of wound infections in compound fractures. PMID- 21017775 TI - Ocular changes in scrub typhus; a study of 451 patients. PMID- 21017776 TI - Neuropsychiatric examination of military personnel recovered from Japanese prison camps. PMID- 21017777 TI - Early management of penetrating wounds of knee joint. PMID- 21017778 TI - Pain in men wounded in battle. PMID- 21017779 TI - Otolaryngology clinic in China-Burma-India theater. PMID- 21017780 TI - The oral and rectal temperatures in hot environments. PMID- 21017781 TI - Milk control program of U.S. forces in Iceland. PMID- 21017782 TI - Isolation of Coccidioides immitis from sputum. PMID- 21017783 TI - Gastro-intestinal studies on the field x-ray machine. PMID- 21017784 TI - Multiple exposures in hand photography. PMID- 21017785 TI - Foreign body localization using sources of light for orientation. PMID- 21017786 TI - Conservative treatment of prognathous mandible. PMID- 21017787 TI - Sympathetic paralysis in peripheral nerve leprosy. PMID- 21017789 TI - Apparatus for photomicrography or microprojection. PMID- 21017788 TI - Penicillin therapy in fatal case of equine tetanus. PMID- 21017790 TI - The etiology and treatment of blepharitis; a study in military personnel. PMID- 21017791 TI - The functions of medical units in amphibious operations. PMID- 21017792 TI - Three and one-half years of nutrition activities in the Eighth Service Command. PMID- 21017793 TI - Blood; war to peace. PMID- 21017794 TI - March fracture of the inferior pubic ramus. PMID- 21017795 TI - The military importance of low back disability. PMID- 21017797 TI - Biological warfare. PMID- 21017796 TI - Note on the use of dextrose, 5 per cent in sterile distilled water (item no. 1164600) as a stock standard solution in the blood sugar determination. PMID- 21017798 TI - ARMY Institute of Pathology; Army Medical Museum. PMID- 21017799 TI - NAVY cholera research. PMID- 21017800 TI - Malaria. PMID- 21017801 TI - Studies of relapse in malaria. PMID- 21017802 TI - Observations on malaria in Italy (1943-1944). PMID- 21017803 TI - Some aspect of experimental malaria therapy. PMID- 21017804 TI - Malaria in the Polish forces in the East and in Italy. PMID- 21017805 TI - War wounds of the heart. PMID- 21017806 TI - Experiments in diphtheria immunization. PMID- 21017807 TI - Fatty diarrhoea. PMID- 21017809 TI - Kala azar. PMID- 21017808 TI - The diagnosis and treatment of kala azar. PMID- 21017810 TI - Infective hepatitis. PMID- 21017811 TI - A summary of the studies on infectious hepatitis in NATOUSA during 1944. PMID- 21017812 TI - Infective hepatitis. PMID- 21017813 TI - War wounds of the chest on the Adriatic sector. PMID- 21017814 TI - Clotted haemothorax. PMID- 21017815 TI - Medical aspects of penetrating wounds of the chest. PMID- 21017816 TI - Radiology in trauma chest cases. PMID- 21017817 TI - Diagnosis and treatment of amoebiasis. PMID- 21017818 TI - Amoebiasis. PMID- 21017820 TI - Foot conditions due to cold and wet. PMID- 21017819 TI - Diagnosis and treatment of amoebiasis. PMID- 21017821 TI - Trench foot. PMID- 21017822 TI - Trench foot. PMID- 21017824 TI - Diphtheria. PMID- 21017823 TI - Diphtheria. PMID- 21017825 TI - Diphtheria. PMID- 21017826 TI - Use of penicillin in the carrier stage of faucial diphtheria; interim report of its use in a group of 47 cases. PMID- 21017827 TI - Infectious polyneuritis. PMID- 21017828 TI - The problem of the inadequate personality. PMID- 21017829 TI - The work of a corps psychiatrist on the Italian front. PMID- 21017830 TI - Gastro-intestinal disorders of psychogenic origin. PMID- 21017831 TI - Medical uses of penicillin. PMID- 21017832 TI - Medical uses of penicillin. PMID- 21017833 TI - Penicillin in dermatology. PMID- 21017834 TI - The primary operation in battle wounds of the limbs. PMID- 21017835 TI - The primary treatment of wounds. PMID- 21017836 TI - Delayed primary suture of flesh wounds. PMID- 21017837 TI - Synopsis of the results of treatment of 288 cases of open fracture of the femoral shaft, Feb. 1944 to Jan. 1945. PMID- 21017839 TI - Early closure of compound fractures. PMID- 21017838 TI - War wounds involving the femur. PMID- 21017840 TI - The closure of amputation stumps. PMID- 21017841 TI - Late closure of wounds. PMID- 21017842 TI - The role of penicillin in war wounds. PMID- 21017843 TI - Wounds of the scalp. PMID- 21017844 TI - Primary closure of battle wounds of the face. PMID- 21017845 TI - Summary of the results of wound closure after Gothic Line battle. PMID- 21017846 TI - The surgery of lodged intrathoracic missiles. PMID- 21017847 TI - Clotted haemothorax. PMID- 21017848 TI - Post-operative treatment of chest wounds in forward areas. PMID- 21017850 TI - The diagnosis of abdominal trauma in warfare. PMID- 21017849 TI - Thoracic trauma. PMID- 21017851 TI - The treatment of wounds of the large intestine. PMID- 21017852 TI - Thoraco-abdominal wounds. PMID- 21017853 TI - Abdominal injuries after evacuation to a base hospital. PMID- 21017854 TI - Injuries to the colon. PMID- 21017855 TI - Anaesthesia in abdominal operations. PMID- 21017856 TI - A summary of the results of abdominal surgery in CMF. PMID- 21017857 TI - The organisation of a convalescent depot. PMID- 21017858 TI - Missile injuries of the urethra. PMID- 21017859 TI - Burns. PMID- 21017860 TI - Observations on altered protein metabolism after thermal injury. PMID- 21017861 TI - The relationship of wound healing and protein metabolism. PMID- 21017862 TI - Plasma protein levels in chronic sepsis. PMID- 21017863 TI - A plea for conservatism in the primary surgery of wounds of the main arteries of the limbs. PMID- 21017864 TI - Forward surgery of injuries to major blood vessels. PMID- 21017865 TI - The problem of wound excision in the treatment of vascular injuries. PMID- 21017866 TI - Gas gangrene. PMID- 21017867 TI - Primary skull closure with acrylic plates. PMID- 21017868 TI - Deep intraocular infection due to mines. PMID- 21017869 TI - The treatment of wounds involving the temporal bone. PMID- 21017870 TI - The importance of the post-operative blood pressure. PMID- 21017871 TI - Hazards of transfusion. PMID- 21017872 TI - The use of concentrated plasma in the treatment of pulmonary oedema due to trauma. PMID- 21017873 TI - Foot strain. PMID- 21017874 TI - Bacterial flora of war wounds and penicillin therapy. PMID- 21017875 TI - Chronic sepsis with toxaemia in war wounds. PMID- 21017876 TI - Abstract of treatment of 1,000 jaw wounds. PMID- 21017877 TI - Factors influencing the closure of battle wounds. PMID- 21017878 TI - Injuries around the ankle joint occurring in parachutists. PMID- 21017879 TI - [Not Available]. PMID- 21017880 TI - [Not Available]. PMID- 21017881 TI - [Not Available]. PMID- 21017882 TI - [Not Available]. PMID- 21017884 TI - Report of two hundred necropsies on natives of Okinawa. PMID- 21017883 TI - Dysentery outbreak aboard naval vessels in San Pedro Bay, Philippine Islands. PMID- 21017885 TI - Tropical headache; preliminary report on diagnosis and treatment. PMID- 21017886 TI - Headache; an etiologic approach; with special reference to the so-called vacuum headache. PMID- 21017887 TI - Causes of uniocular and binocular blindness in the U.S. Navy and U.S. Marine Corps in World War II. PMID- 21017888 TI - Shigellosis studies; etiology and clinical features. PMID- 21017889 TI - Epidemiologic study of epidemic hepatitis. PMID- 21017890 TI - The copper ionization treatment of fungous infections. PMID- 21017891 TI - Abdominal war wounds; report of ten cases with recovery. PMID- 21017892 TI - Case of keloid. PMID- 21017893 TI - Horner's syndrome following gunshot wound of the neck. PMID- 21017894 TI - Aggravation of bacterids by penicillin; with a theory as to causation. PMID- 21017895 TI - Ischemic muscle damage. PMID- 21017896 TI - Meningococcic meningitis with severe cerebral involvement. PMID- 21017897 TI - Malignant granulocytopenia treated with penicillin. PMID- 21017898 TI - Plastic reconstruction of lip following gunshot wound. PMID- 21017899 TI - Glass stirring rod in urethra and bladder. PMID- 21017901 TI - Handle for aural speculum. PMID- 21017900 TI - Electrocardiographic changes in carbon tetrachloride poisoning. PMID- 21017902 TI - Modivication of the Zimmer clamp for cranial skeletal traction. PMID- 21017903 TI - Streamlined foot baths. PMID- 21017904 TI - Report of food-borne streptococcus outbreak. PMID- 21017905 TI - Soybean milk-substitute as used on Okinawa. PMID- 21017906 TI - Production and properties of 2,3-butanediol; the effect of various nutrient materials on the fermentation of starch by Aerobacillus polymyxa. PMID- 21017907 TI - Dried whole egg powder; the keeping quality of acidulated, gas-packed powders of low moisture content. PMID- 21017908 TI - The effect of wheat germ oil antioxidants and natural reducing substances on the stability of whole milk powder. PMID- 21017909 TI - Dried milk powder; the effect of storage temperature, moisture content, and plant source on the keeping quality of milk powders of different fat levels. PMID- 21017910 TI - The keeping quality of dehydrated mixtures of egg and milk. PMID- 21017911 TI - The occurrence and distribution of Salmonella types in fowl; isolation from hen's eggs. PMID- 21017912 TI - A compact carbon pile rheostat. PMID- 21017913 TI - Resin-rubber from Canadian grown plants; analytical study of milkweed pod gum. PMID- 21017914 TI - Carotene content of the corn plant. PMID- 21017915 TI - Cyclic acetals of the carbohydrates. PMID- 21017916 TI - A new African species of Paurocephala Crawford (Homoptera; Psyllidae; Pauropsyllinae). PMID- 21017917 TI - Resuscitation of the nematode Tylenchus polyhypnus, n.sp., after almost 39 years' dormancy. PMID- 21017919 TI - Climate and insect life. PMID- 21017918 TI - Spectroscopic study of the permeability and lysis of red blood corpuscles. PMID- 21017920 TI - Development of a chemotherapy for systemic arsenical poisoning. PMID- 21017921 TI - Electrochemistry of uranium. PMID- 21017922 TI - Patterson distributions and native protein crystallography. PMID- 21017923 TI - Origin of ion burn in cathode ray tubes. PMID- 21017924 TI - Entropy and elasticity in keratin and myosin. PMID- 21017925 TI - Presence of a delta 5-unsaturated sterol derivative in the medulla cells of keratin fibres. PMID- 21017926 TI - Blood group A substances in commercial hog stomach powder. PMID- 21017927 TI - A substitute for annatto in butter. PMID- 21017928 TI - Academic scientific men and consultants. PMID- 21017929 TI - Physical methods for the identification of materials. PMID- 21017930 TI - Mite-typhus and the new mitetyphus vaccine. PMID- 21017931 TI - Biological properties of Bacillus subtilis. PMID- 21017932 TI - Some uses of D.D.T. in agriculture. PMID- 21017933 TI - A lunar effect on cosmic rays? PMID- 21017934 TI - Reversible conversion of amino- into anhydro-sugars. PMID- 21017935 TI - A method of testing the anti-malarial properties of compounds in vitro. PMID- 21017936 TI - Chemical production of mutations. PMID- 21017937 TI - Hermaphroditism in a terrestrial isopod. PMID- 21017938 TI - Authenticity of scientific anecdotes. PMID- 21017939 TI - Effect of some fatty acids on the oxygen uptake of Mycobact. tubercul.hum. in relation to their bactericidal action. PMID- 21017940 TI - Discovery of elements 95 and 96 and the chemical properties of the transuranic elements. PMID- 21017941 TI - Alcohol and creative work; painters. PMID- 21017942 TI - Studies of compulsive drinkers; psychological test results. PMID- 21017943 TI - Cultural differences in rates of alcoholism. PMID- 21017944 TI - A public clinic approach to certain aspects of alcoholism. PMID- 21017945 TI - A survey of official Church statements on alcoholic beverages. PMID- 21017946 TI - A JUDGE'S viewpoint on narcotic addicts before the court, with comment on its applicability to alcoholics. PMID- 21017947 TI - High speed photography of the cathode-ray tube. PMID- 21017948 TI - Thickness measurement of thin coatings by x-ray absorption. PMID- 21017949 TI - A simple carbon dioxide vapor pressure thermometer. PMID- 21017950 TI - POLARIMETER. PMID- 21017951 TI - Hemolytic streptococcal sore throat; antibody response following treatment with penicillin, sulfadiazine, and salicylates. PMID- 21017952 TI - Blood levels of penicillin after oral administration with various antacides. PMID- 21017953 TI - Studies on the toxicity of streptomycin for man; a preliminary report. PMID- 21017954 TI - Complement-fixing and neutralizing antibodies against Japanese B virus in the sera of Okinawan horses. PMID- 21017955 TI - The absorption of orally administered penicillin. PMID- 21017956 TI - Effect of penicillin on growth of Alcaligenes fecalis. PMID- 21017957 TI - Intravenous utilization of partial acid hydrolysates of proteins. PMID- 21017958 TI - The presence in normal serum of inhibiting subsequences against Bacillus subtilis. PMID- 21017959 TI - Preliminary studies on the absorption and excretion of streptomycin in dogs. PMID- 21017960 TI - The activity of streptomycin in experimental syphilis. PMID- 21017961 TI - Competition between two entomogenous bacteria. PMID- 21017962 TI - A new steric effect in organic chemistry. PMID- 21017963 TI - The detoxification by acetylation of soluble antigens from Shigella dysenteriae (Shiga) and E. typhosa. PMID- 21017964 TI - On the blocking antibody and the zone phenomenon in human anti-Rh sera. PMID- 21017965 TI - Relapses following delayed treatment of naturally induced vivax malaria of Pacific origin. PMID- 21017966 TI - Assay of p-aminobenzoic acid. PMID- 21017967 TI - Antagonism of salicylate by pantoyltaurine. PMID- 21017968 TI - Interference with the antibacterial action of streptomycin by reducing agents. PMID- 21017969 TI - Water-level regulator for a series of high-temperature water-baths. PMID- 21017970 TI - Thromboplastic studies on hemophilia. PMID- 21017971 TI - Rediscovery of vitamin A. PMID- 21017972 TI - Inactive (non-oxygen-combining) hemoglobin in the blood of ophidia and dogs. PMID- 21017973 TI - The reciprocal relationship of man and his ideological milieu; a primal scene from ancient Egypt and its role in the genesis of a cosmology. PMID- 21017974 TI - The transformation of impulses into the obsessional ritual. PMID- 21017975 TI - [Not Available]. PMID- 21017976 TI - [Not Available]. PMID- 21017977 TI - [Not Available]. PMID- 21017978 TI - [Not Available]. PMID- 21017979 TI - [Not Available]. PMID- 21017980 TI - [Not Available]. PMID- 21017981 TI - [Not Available]. PMID- 21017982 TI - Narcoanalysis and sub-shock insulin in the treatment of anorexia nervosa. PMID- 21017983 TI - [Not Available]. PMID- 21017984 TI - [Not Available]. PMID- 21017985 TI - The discharging lesion in neurology. PMID- 21017986 TI - A case of topographical disorientation associated with a unilateral cerebral lesion. PMID- 21017987 TI - [Not Available]. PMID- 21017988 TI - The development of the human lateral geniculate body. PMID- 21017989 TI - MENNINGER Foundation School of Psychiatry. PMID- 21017990 TI - A note on the treatment of depressive psychoses in soldiers. PMID- 21017991 TI - Bibliotherapy for neuropsychiatric patients; report of two cases. PMID- 21017992 TI - Syphilitic amyotrophy; clinical study of seven cases. PMID- 21017993 TI - Psychiatric social work in the American Red Cross. PMID- 21017994 TI - Psychiatric aspects of head injury. PMID- 21017995 TI - [Not Available]. PMID- 21017996 TI - [Not Available]. PMID- 21017997 TI - Aphasia, apraxia, and agnosia; a new classification. PMID- 21017998 TI - Psychogenic vomiting. PMID- 21017999 TI - Paramyoclonus multiplex of Friedreich. PMID- 21018000 TI - Organic thinking difficulty. PMID- 21018001 TI - The present status of narco-diagnosis and therapy. PMID- 21018002 TI - Therapeutic relaxation. PMID- 21018003 TI - Psychopathy in the scheme of human typology. PMID- 21018004 TI - The value of formal psychiatric examinations in the criminal court. PMID- 21018005 TI - Traumatic intracerebral hematoma. PMID- 21018006 TI - A simple practical test for anxiety neurosis. PMID- 21018008 TI - [Not Available]. PMID- 21018007 TI - [Not Available]. PMID- 21018009 TI - [Not Available]. PMID- 21018010 TI - Phyletic manifestations and reversions. PMID- 21018011 TI - Penicillin in early syphilis. PMID- 21018012 TI - Sudden graying of hair, alopecia, and diabetes mellitus of psychogenic origin. PMID- 21018013 TI - Narcosynthesis for the civilian neurosis. PMID- 21018014 TI - The mechanism of reactivation in depressions of the old age group; with three case reports. PMID- 21018015 TI - A study of the art work of a behavior-problem boy as it relates to ego development and sexual enlightment. PMID- 21018016 TI - Psychosomatic problems as seen in internal medicine. PMID- 21018017 TI - New aspects of two old neurological problems. PMID- 21018018 TI - A deceptive psychoneurosis. PMID- 21018019 TI - A cleanliness test devised by a stutterer. PMID- 21018020 TI - The psychopathology of psychotic-like reactions in the combat soldier. PMID- 21018021 TI - [Not Available]. PMID- 21018022 TI - [Not Available]. PMID- 21018023 TI - [Not Available]. PMID- 21018024 TI - [Not Available]. PMID- 21018025 TI - [Not Available]. PMID- 21018026 TI - [Not Available]. PMID- 21018027 TI - [Not Available]. PMID- 21018028 TI - [Not Available]. PMID- 21018029 TI - [Not Available]. PMID- 21018030 TI - [Not Available]. PMID- 21018031 TI - [Not Available]. PMID- 21018032 TI - [Not Available]. PMID- 21018033 TI - [Not Available]. PMID- 21018034 TI - [Not Available]. PMID- 21018035 TI - [Not Available]. PMID- 21018036 TI - Diathermic surgery of the ciliary body in glaucoma; experimental and clinical observations. PMID- 21018037 TI - A case of atypical achromatopsia. PMID- 21018038 TI - Ocular leprosy in Panama; a study of 150 cases. PMID- 21018039 TI - Superficial pigmentation of the cornea. PMID- 21018040 TI - Glioma of the optic nerve. PMID- 21018041 TI - The relationship between light adaptation and dark adaptation and its significance for appraisal of the glare effect of different illuminants. PMID- 21018042 TI - The control of experimental anterior-chamber infections with systemic penicillin therapy. PMID- 21018043 TI - Hydrops of the cornea. PMID- 21018044 TI - X-ray burns complicated by glaucoma. PMID- 21018045 TI - Dislocation of lens into anterior chamber. PMID- 21018046 TI - Early multiple sclerosis. PMID- 21018047 TI - Iridocapsulotomy for postoperative membranes. PMID- 21018048 TI - Possible errors in the use of the crossed cylinder. PMID- 21018049 TI - The intensive course for ophthalmologic training. PMID- 21018050 TI - Opportunities for training in ophthalmology. PMID- 21018051 TI - [Not Available]. PMID- 21018052 TI - [Not Available]. PMID- 21018053 TI - [Not Available]. PMID- 21018054 TI - A basket type implant for use after enucleation. PMID- 21018055 TI - Uveal blastomycosis. PMID- 21018056 TI - Acid burns of the eye. PMID- 21018057 TI - Tests for detection and analysis of color blindness; comparison of editions of the Ishihara test. PMID- 21018058 TI - Edema of cornea precipitated by quinacrine (atabrine). PMID- 21018059 TI - Return of vision in transplanted adult salamander eyes after seven days of refrigeration. PMID- 21018060 TI - Ocular dermatitis from local penicillin; report of two cases. PMID- 21018062 TI - Corneal transplantation and preliminary iridectomy. PMID- 21018061 TI - Congenital malformations induced in rats by maternal vitamin A deficiency; defects of the eye. PMID- 21018063 TI - Contact eye cup corneal baths with solutions of penicillin. PMID- 21018064 TI - Traumatic liporrhagia retinalis. PMID- 21018065 TI - Penicillin and vitamin C in the treatment of hypopyon ulcer. PMID- 21018066 TI - The intra-ocular use of penicillin. PMID- 21018067 TI - Penicillin in ophthalmology; the bacteriological, experimental, and clinical evidence of its value, including a personal series of 125 clinical cases. PMID- 21018068 TI - Penicillin treatment of ocular inflammation. PMID- 21018069 TI - Thrombin technique in ophthalmic surgery. PMID- 21018070 TI - Survey of the treatment of traumatic corneal ulcer, 1941-1944, Royal Hospital, Sheffield. PMID- 21018071 TI - Testing the hearing of young children. PMID- 21018072 TI - Treatment of acute pharyngeal infections by insufflation of sulfanilamide powder. PMID- 21018073 TI - Xanthoma or lipoid granuloma of the temporal bone (Hand-Christian-Schuller syndrome). PMID- 21018075 TI - Anomalous antral tooth. PMID- 21018074 TI - Some interesting lesions of the tongue. PMID- 21018076 TI - Maxillary sinusitis and ethmoiditis of the right side developing during intramuscular injection of penicillin for pansinusitis of the left side. PMID- 21018078 TI - Otosclerosis. PMID- 21018077 TI - Plastic repair of a large alveolar-antral fistula. PMID- 21018079 TI - Advances in the understanding of rhinologic and otologic conditions related to the nervous system; a critical survey of recent literature. PMID- 21018080 TI - Practical aids in refraction. PMID- 21018081 TI - Plastic surgery in congenital deformities about the face. PMID- 21018082 TI - Sinusitis and toxic neuritis. PMID- 21018083 TI - Reflex headaches of nasal origin. PMID- 21018084 TI - Treatment of secondary glaucoma. PMID- 21018085 TI - On ocular pads. PMID- 21018086 TI - Plastic surgery in congenital deformities about the face. PMID- 21018087 TI - Report of the employment survey conducted by the American Society for the Hard of Hearing. PMID- 21018089 TI - Some observations on the etiology of foreign bodies in the oesophagus. PMID- 21018088 TI - Reflections on the radical mastoid operation, with a description of the technique evolved from my experience. PMID- 21018090 TI - A case of mediastinitis. PMID- 21018091 TI - Rhinoliths; the report of an antral and three nasal stones. PMID- 21018092 TI - Hydrops of labyrinth (Meniere's disease); diagnosis; results of labyrinth surgery. PMID- 21018093 TI - Habituation to caloric vestibular stimulation. PMID- 21018094 TI - The closure of oromaxillary fistulae; a preliminary report. PMID- 21018095 TI - The use of thrombin in rhinologic surgery; a preliminary report. PMID- 21018096 TI - Tinnitus, deafness and dizziness. PMID- 21018097 TI - [Not Available]. PMID- 21018098 TI - Auricular training is here to stay. PMID- 21018099 TI - Gynecomastia. PMID- 21018100 TI - Studies on the early changes in the livers of rats treated with various toxic agents, with especial reference to the vascular lesions; the histology of the rat's liver in allyl formate poisoning. PMID- 21018101 TI - Primary tumor of the heart containing epithelium-like elements. PMID- 21018102 TI - Gross vascularity of the mitral valve as a stigma of rheumatic heart disease. PMID- 21018103 TI - Observations on the pathological changes produced by a toxic substance present in blue-green algae (Microcystis aeruginosa). PMID- 21018104 TI - The nephrotoxic action of dl-serine as related to certain dietary factors. PMID- 21018105 TI - Ceroid pigment in human tissues. PMID- 21018106 TI - Studies on chancroid; observations on the histology with an evaluation of biopsy as a diagnostic procedure. PMID- 21018107 TI - The problem of human toxoplasma carriers. PMID- 21018108 TI - The inunction of allergens with intraderm; desensitization by allergen inunctions. PMID- 21018109 TI - Pollinosis in Brazil. PMID- 21018110 TI - Airborne fungi in allergic disease; survey of airborne fungi in the San Antonio, Texas, area; incidence of skin reactions with mold extracts. PMID- 21018111 TI - Studies on tissue tolerance to a new glycerol peroxide antiseptic solution. PMID- 21018112 TI - Laryngeal obstruction with asthmatic symptoms; report of a case. PMID- 21018113 TI - Drug sensitivity on a nonspecific basis. PMID- 21018114 TI - Pollen antigens; critical review of literature. PMID- 21018115 TI - Distribution of lipase in the tissues under normal and under pathologic conditions. PMID- 21018116 TI - Experimental studies in cardiovascular pathology; atheromatosis in dogs following repeated intravenous injections of solutions of hydroxyethylcellulose. PMID- 21018117 TI - Experimental studies in cardiovascular pathology; vibratory lability of plasma colloids in rabbits and in dogs following ingestion of cholesterol. PMID- 21018118 TI - Structural changes in the thyroid glands of patients treated with thiouracil. PMID- 21018119 TI - Sclerema adiposum neonatorum of both internal and external adipose tissue. PMID- 21018120 TI - Alveolar cell tumor of the lung; further evidence of its bronchiolar origin. PMID- 21018121 TI - Experimental nephropathies; the problem of experimental glomerulonephritis. PMID- 21018122 TI - Pituitary lesions accompanying obesity. PMID- 21018123 TI - Adenocanthoma of the stomach. PMID- 21018124 TI - Mumps; use of convalescent serum in the treatment and prophylaxis of orchitis. PMID- 21018125 TI - Pathogenesis of congenital hemolytic disease (erythroblastosis fetalis); theoretic considerations. PMID- 21018126 TI - Pathogenesis of congenital hemolytic disease (erythroblastosis fetalis); illustrative case histories of Rh sensitization. PMID- 21018127 TI - Sucking response of newly born babies at breast; a study of fifty cases. PMID- 21018128 TI - Kaposi's varicelliform eruption; studies on etiology. PMID- 21018129 TI - Prolonged tachycardia. PMID- 21018131 TI - [Not Available]. PMID- 21018130 TI - Thrombosis of the pulmonary artery in children; report of a case with a review of the literature. PMID- 21018132 TI - [Not Available]. PMID- 21018133 TI - [Not Available]. PMID- 21018134 TI - [Not Available]. PMID- 21018135 TI - [Not Available]. PMID- 21018136 TI - [Not Available]. PMID- 21018137 TI - [Not Available]. PMID- 21018138 TI - [Not Available]. PMID- 21018139 TI - [Not Available]. PMID- 21018140 TI - [Not Available]. PMID- 21018141 TI - Infection in infancy. PMID- 21018142 TI - The clinical material of health in paediatrics; where to get it, and how to use it. PMID- 21018143 TI - The nature of Still's disease; with report of a case. PMID- 21018144 TI - Decrease of serum cholesterol ester in haemolytic disease of the newborn. PMID- 21018145 TI - Osteomyelitis of the jaws in infancy treated with penicillin. PMID- 21018146 TI - The measurement of the nutritional level of thiamin in children by the estimation of the urinary excretion. PMID- 21018147 TI - Idiopathic muscular hypertrophy of oesophagus, pylorus, duodenum and jejunum in a young girl. PMID- 21018148 TI - Cystic fibrosis of the pancreas. PMID- 21018149 TI - An experiment in control of neo-natal infections in a maternity hospital. PMID- 21018150 TI - Aleukemic lymphatic leukemia in childhood with sulfonamide sensitivity; report of case. PMID- 21018151 TI - Compression myelitis due to subperiosteal typhoid abscess. PMID- 21018152 TI - Contagious diarrhea of the newborn with special emphasis on treatment. PMID- 21018153 TI - The local treatment of pertussis. PMID- 21018154 TI - Acute poliomyelitis; encephalic, bulbar, spinal. PMID- 21018156 TI - [Not Available]. PMID- 21018155 TI - Pertussis with lung abscess. PMID- 21018157 TI - [Not Available]. PMID- 21018158 TI - [Not Available]. PMID- 21018159 TI - [Not Available]. PMID- 21018160 TI - [Not Available]. PMID- 21018161 TI - [Not Available]. PMID- 21018162 TI - [Not Available]. PMID- 21018163 TI - [Not Available]. PMID- 21018164 TI - [Not Available]. PMID- 21018165 TI - [Not Available]. PMID- 21018166 TI - To promote child welfare in other American republics; Children's Bureau gives advisory service to children's agencies on their request. PMID- 21018167 TI - Lipemic nephrosis. PMID- 21018168 TI - The induction of vitamin C subnutrition; a comparison of intradermal tests with plasma ascorbic acid levels. PMID- 21018169 TI - A vision test for pediatrician's use. PMID- 21018170 TI - Oral plasma feeding; a preliminary report on neonatal feedings. PMID- 21018171 TI - The use of gentian violet in children infected with Ascaris lumbricoides. PMID- 21018172 TI - Toxoplasmosis in a large Minnesota family. PMID- 21018173 TI - A comparative study of the immune response to various pertussis antigens and the disease. PMID- 21018174 TI - One dose subcutaneous sodium sulfadiazine for acute infections. PMID- 21018175 TI - Comparison of absorption of vitamin A after oral and intramuscular administration in normal children. PMID- 21018176 TI - Lacunar skull of the newborn infant. PMID- 21018177 TI - Displacement of the mediastinum due to pulsion by a caseous tuberculous lung without pleural effusion; report of a case in an infant. PMID- 21018178 TI - Agenesis of the lung; case report. PMID- 21018179 TI - Atelectasis of the newborn; treatment by bronchoscopic drainage. PMID- 21018180 TI - Listerella meningitis; report of a case with recovery. PMID- 21018181 TI - Congenital ectoderman defect; report of an unusual case involving scalp and leg. PMID- 21018182 TI - Medical education; proposal for decentralized medical teaching as an aid in improving medical care. PMID- 21018183 TI - [Not Available]. PMID- 21018184 TI - [Not Available]. PMID- 21018185 TI - [Not Available]. PMID- 21018186 TI - [Not Available]. PMID- 21018187 TI - [Not Available]. PMID- 21018188 TI - [Not Available]. PMID- 21018189 TI - [Not Available]. PMID- 21018190 TI - [Not Available]. PMID- 21018191 TI - [Not Available]. PMID- 21018192 TI - [Not Available]. PMID- 21018193 TI - [Not Available]. PMID- 21018194 TI - [Not Available]. PMID- 21018195 TI - Facts about marihuana; a survey of the literature. PMID- 21018196 TI - Famous coincidences of science. PMID- 21018197 TI - Resistance of Staphylococcus aureus cultured in semi-synthetic and F.D.A. media. PMID- 21018198 TI - Insect and rodent control. PMID- 21018199 TI - DRUG therapy of epilepsy. PMID- 21018201 TI - RUTIN to be commercially available for hypertension. PMID- 21018200 TI - ANTIHISTAMINE substances and benadryl in allergy. PMID- 21018202 TI - NEWER antimalarials. PMID- 21018203 TI - [Not Available]. PMID- 21018204 TI - [Not Available]. PMID- 21018205 TI - [Not Available]. PMID- 21018206 TI - [Not Available]. PMID- 21018207 TI - [Not Available]. PMID- 21018208 TI - [Not Available]. PMID- 21018209 TI - [Not Available]. PMID- 21018210 TI - [Not Available]. PMID- 21018211 TI - [Not Available]. PMID- 21018212 TI - [Not Available]. PMID- 21018213 TI - Benadryl. PMID- 21018214 TI - TRIDIONE: a modern drug effective in forms of epilepsy resistant to ordinary medication. PMID- 21018215 TI - The chemical nature of penicillin. PMID- 21018216 TI - New organic insecticides. PMID- 21018217 TI - The place of pollen analysis in paleo-ecology. PMID- 21018218 TI - The principle of priority in biological nomenclature. PMID- 21018219 TI - The work of the botanists of Cinchona Mission in Colombia. PMID- 21018220 TI - The new chemistry and technology of oils and fats. PMID- 21018221 TI - Scientific publications and the indexer. PMID- 21018222 TI - On the genus Aloe. PMID- 21018223 TI - [Not Available]. PMID- 21018224 TI - Surface-active agents as ointment bases. PMID- 21018225 TI - The beta-hydroxy and beta-halo ethyl 3- and 4-nitro phthalimides. PMID- 21018226 TI - Studies on the local anesthetic properties of isonipecaine. PMID- 21018227 TI - Erythrina alkaloids; a colorimetric determination of beta-erythroidine. PMID- 21018228 TI - A contribution to the chemistry and pharmacology of glycolanilide. PMID- 21018229 TI - A drop-counter for saline solutions. PMID- 21018231 TI - U.S.P. melting point reference standards. PMID- 21018230 TI - Properties of a new mercurial antiseptic, 2-acetoxymercuri-4-diisobutylphenol. PMID- 21018232 TI - A method for large-scale testing for pyrogens. PMID- 21018233 TI - The evaluation of various bases for sulfonamide ointments. PMID- 21018234 TI - The separation of acetylsalicylic acid, acetophenetidin, and caffeine. PMID- 21018235 TI - Action of cholic-, desoxycholic-, dehydrocholic-, and dehydrodesoxycholic acids on body temperature in rabbits. PMID- 21018236 TI - Peroxide test for mineral oils. PMID- 21018237 TI - Effect of time and temperature in the preparation of certain fats and waxes for melting point determinations. PMID- 21018238 TI - Effect of time and temperature in the preparation of certain fats and waxes for melting point determination. PMID- 21018239 TI - The toxicity of myristyl-gamma-picolinium chloride. PMID- 21018240 TI - Tables for the microscopic identification of N.F. VII crystalline substances. PMID- 21018241 TI - Enzyme theory of drug action. PMID- 21018242 TI - MOTION sickness; hyoscine best preventive of travel ills now known but its effectiveness is limited. PMID- 21018243 TI - Progress in vitamin therapy. PMID- 21018244 TI - Preliminary report on magnesium trisilicate as an emulsifier. PMID- 21018245 TI - [Not Available]. PMID- 21018246 TI - The determination of the minimal lethal dose and the average rate of uptake of G strophantin and digitoxin in the heart-lung preparation of the dog. PMID- 21018247 TI - Further study of some l-substituted theobromine compounds. PMID- 21018248 TI - The effects of thiouracil on the hematopoietic system of the albino rat. PMID- 21018249 TI - The relationship between chemical structure and spasmolytic action of some new anticolinergic esters. PMID- 21018250 TI - Anesthesia; the anesthetic action of n-propylmethyl ether. PMID- 21018251 TI - Metabolic studies on derivatives of beta-phenylethylamine. PMID- 21018252 TI - Some toxicological and pharmacological properties of streptomycin. PMID- 21018253 TI - The antagonism between atropine and strychnine in the mouse. PMID- 21018254 TI - Electrocardiographic correlations with digitalis bioassay. PMID- 21018255 TI - A study on the development of tolerance and cross tolerance to barbiturates in experimental animals. PMID- 21018256 TI - Preliminary studies of the anesthetic activity of fluorinated hydrocarbons. PMID- 21018257 TI - Biological aspects of emulsions. PMID- 21018259 TI - Electrolytic potassium permanganate. PMID- 21018258 TI - Pharmaceutical and other uses for ethylene and propylene glycols. PMID- 21018260 TI - Some medicinal barbiturates and their identification. PMID- 21018261 TI - Advantages of a standardisation laboratory. PMID- 21018262 TI - EFFECT of synthetic rubber tubing on penicillin. PMID- 21018263 TI - Scientific research and industrial planning. PMID- 21018264 TI - Control of insect pests. PMID- 21018266 TI - DETERGENTS and detergency; third report. PMID- 21018265 TI - CHEMOTHERAPY: second report. PMID- 21018267 TI - The assay of emetine hydrochloride; a modified method. PMID- 21018268 TI - The preparation of sterile medicaments. PMID- 21018269 TI - The preparation of non-pyrogenic saline infusion fluids. PMID- 21018270 TI - Tests on non-pyrogenic fluids. PMID- 21018271 TI - Bacterial filtration; some experiences. PMID- 21018272 TI - The pharmacy of penicillin. PMID- 21018273 TI - [Not Available]. PMID- 21018274 TI - [Not Available]. PMID- 21018275 TI - [Not Available]. PMID- 21018276 TI - DRUG therapy and diagnosis of neurologic disorders. PMID- 21018277 TI - MENOPAUSE. PMID- 21018279 TI - [Not Available]. PMID- 21018278 TI - [Not Available]. PMID- 21018280 TI - [Not Available]. PMID- 21018281 TI - [Not Available]. PMID- 21018282 TI - Studies on thiouracils; quantitative acidimetric determination of 2-thiouracil and 4-methyl-2-thiouracil. PMID- 21018283 TI - [Not Available]. PMID- 21018284 TI - [Not Available]. PMID- 21018285 TI - [Not Available]. PMID- 21018286 TI - [Not Available]. PMID- 21018287 TI - [Not Available]. PMID- 21018288 TI - [Not Available]. PMID- 21018290 TI - [Not Available]. PMID- 21018289 TI - [Not Available]. PMID- 21018291 TI - [Not Available]. PMID- 21018292 TI - [Not Available]. PMID- 21018294 TI - A study of some conditions influencing the rate of exchange of oxygen in blood in vitro. PMID- 21018293 TI - The effect of section of the supraoptico-hypophyseal tracts on the inhibition of water-diuresis by emotional stress. PMID- 21018295 TI - The action of haemolysins on normal and pathological human erythrocytes. PMID- 21018297 TI - [Not Available]. PMID- 21018296 TI - A biochemical study of isolated perfused lungs with special reference to the effects of phosgene. PMID- 21018298 TI - [Not Available]. PMID- 21018299 TI - Conditioning or apprehension in rat learning. PMID- 21018301 TI - The performance of rhesus monkeys on series of object-quality and positional discriminations and discrimination reversals. PMID- 21018300 TI - The copulatory behavior of the golden hamster. PMID- 21018302 TI - Motor criteria of discrimination. PMID- 21018303 TI - Fear as an intervening variable in avoidance conditioning. PMID- 21018304 TI - Aggressive behavior in the rat; submission as determined by conditioning, extinction, and disuse. PMID- 21018305 TI - The picture-association method and its application in a study of reactions to frustration. PMID- 21018306 TI - The world of experience; its scientific significance. PMID- 21018307 TI - Recall in the thematic apperception test; an experimental investigation into the meaning of recall of phantasy with reference to personality diagnosis. PMID- 21018308 TI - The pathogenesis and treatment of homosexual disorders; a digest of some pertinent evidence. PMID- 21018309 TI - The relative effectiveness of paper-pencil test, interview, and ratings as techniques for personality evaluation. PMID- 21018310 TI - An experiment in group guidance. PMID- 21018311 TI - The identification of cases of chronic motion sickness during military screening examinations. PMID- 21018312 TI - Season of birth and mental ability of prison inmates. PMID- 21018314 TI - The study of eye movements in reading. PMID- 21018313 TI - Psychological aspects of speech-melody. PMID- 21018315 TI - Color adaptation to 1945. PMID- 21018316 TI - The effects of noise. PMID- 21018317 TI - Studies in time perception. PMID- 21018318 TI - Maximum validity of a test with equivalent items. PMID- 21018319 TI - Factor analysis and body types. PMID- 21018320 TI - Serial correlation. PMID- 21018321 TI - A factorial analysis of olfaction. PMID- 21018322 TI - Graphical and tabular aids for determining sample size when planning experiments which involve comparisons of percentages. PMID- 21018323 TI - A simple graphical method for orthogonal rotation of axes. PMID- 21018324 TI - A new descriptive statistic; the parabolic correlation coefficient. PMID- 21018325 TI - The oil treatment of bedclothes for the control of dust-borne infection; principles underlying the development and use of a satisfactory oil-in-water emulsion. PMID- 21018326 TI - The oil treatment of bedclothes for the control of dust-borne infection; the use of triton oil emulsion (T-13) as a routine laundry procedure. PMID- 21018327 TI - STUDY of the effect of oiled floors and bedding on the incidence of respiratory disease in new recruits. PMID- 21018328 TI - Chemotherapy of filariasis due to Wuchereria bancrofti with neostibosan. PMID- 21018329 TI - Important factors in the epidemiology of schistosomiasis in Leyte. PMID- 21018330 TI - Studies on filariasis; serological relationships between antigenic extracts of Wuchereria bancrofti and Dirofilaria immitis. PMID- 21018331 TI - Human encephalitis of the Western equine type in Minnesota in 1941; clinical and epidemiological study of serologically positive cases. PMID- 21018332 TI - The place of fertility control in public health. PMID- 21018333 TI - Comparison of observed and expected deaths in selective service registrants with negative and positive serologic tests for syphilis. PMID- 21018334 TI - Development of a community rheumatic fever program. PMID- 21018335 TI - Experiences with rheumatic fever in the Army Air Forces. PMID- 21018336 TI - PUBLIC health aspects of dehydrated foods. PMID- 21018337 TI - Teamwork for industrial health. PMID- 21018338 TI - State participation in the evaluation of local health services. PMID- 21018339 TI - Observations concerning the growth of three species of Shigella on bismuth sulfite agar. PMID- 21018340 TI - Venereal disease control. PMID- 21018341 TI - The problem of pure food supply. PMID- 21018342 TI - [Not Available]. PMID- 21018343 TI - [Not Available]. PMID- 21018345 TI - [Not Available]. PMID- 21018344 TI - [Not Available]. PMID- 21018346 TI - [Not Available]. PMID- 21018347 TI - [Not Available]. PMID- 21018348 TI - [Not Available]. PMID- 21018349 TI - [Not Available]. PMID- 21018350 TI - [Not Available]. PMID- 21018351 TI - [Not Available]. PMID- 21018352 TI - The Serological Laboratory of the Quebec Ministry of Health; 25 years of service. PMID- 21018353 TI - Report for the year 1944; Division of Venereal Diseases. PMID- 21018354 TI - Education on venereal diseases. PMID- 21018355 TI - Some Observations on venereal-disease control in the Royal Canadian Air Force. PMID- 21018356 TI - State of health of the people of Canada in 1944. PMID- 21018357 TI - An outbreak of food poisoning in Prince Albert, Saskatchewan. PMID- 21018358 TI - Mortality reductions in Ontario, 1900-1942; diphtheria. PMID- 21018359 TI - Fighting childhood's foe. PMID- 21018360 TI - SUGGESTED school health policies. PMID- 21018361 TI - The American School Health Association. PMID- 21018362 TI - The respiratory function of the blood; man under conditions of stress. PMID- 21018363 TI - The respiratory function of the blood; the transition from placental to pulmonary respiration. PMID- 21018364 TI - INTER-DEPARTMENTAL Committee on Dentistry. PMID- 21018365 TI - A study of cross infections over forty years. PMID- 21018366 TI - Bovine tuberculosis. PMID- 21018367 TI - Problem families. PMID- 21018368 TI - The care of the chronic sick and of the aged. PMID- 21018369 TI - Some recent adviances in midwifery. PMID- 21018370 TI - The premature infant. PMID- 21018371 TI - PUBLIC health service drinking water standards. 1946. PMID- 21018372 TI - The excretion of DDT (2,2-bis-(p-chlorophenyl)-1,1,1-trichloroethane) in man, together with clinical observations. PMID- 21018373 TI - Alterations in the cardiac conduction mechanism in experimental thiamine deficiency. PMID- 21018374 TI - The incidence and distribution of Schistosoma mansoni and other helminths in Puerto Rico. PMID- 21018375 TI - Incidence of the Rh agglutinogen among Puerto Ricans. PMID- 21018376 TI - The fleas of Puerto Rico. PMID- 21018377 TI - Malaria control in the Dominican Republic. PMID- 21018378 TI - Ova of Schistosoma mansoni in purged and unpurged fecal specimens. PMID- 21018379 TI - Poisoning by oleoresin of aspidium; report of a case with post mortem findings. PMID- 21018380 TI - [Not Available]. PMID- 21018381 TI - [Not Available]. PMID- 21018382 TI - [Not Available]. PMID- 21018383 TI - [Not Available]. PMID- 21018384 TI - [Not Available]. PMID- 21018385 TI - [Not Available]. PMID- 21018386 TI - [Not Available]. PMID- 21018387 TI - [Not Available]. PMID- 21018388 TI - [Not Available]. PMID- 21018389 TI - [Not Available]. PMID- 21018390 TI - [Not Available]. PMID- 21018391 TI - [Not Available]. PMID- 21018392 TI - [Not Available]. PMID- 21018393 TI - [Not Available]. PMID- 21018394 TI - [Not Available]. PMID- 21018395 TI - [Not Available]. PMID- 21018396 TI - [Not Available]. PMID- 21018397 TI - Experiments with DDT in filter fly control. PMID- 21018398 TI - Control of trickling filter flies with DDT. PMID- 21018399 TI - Sludge disposal practices at Detroit. PMID- 21018400 TI - The determination of suspended solids in sewage. PMID- 21018401 TI - A critical review of the literature of 1945 on sewage and waste treatment and stream pollution. PMID- 21018402 TI - Stream sanitation. PMID- 21018403 TI - Sewage chlorination; reasons and results. PMID- 21018404 TI - RECENT decline in appendicitis mortality. PMID- 21018405 TI - Sewage and industrial wastes in 1945. PMID- 21018406 TI - The use of calgon at the Bristol, Conn., filter plant. PMID- 21018407 TI - What river pollution is costing Wheeling, W. Va. PMID- 21018408 TI - Direct reading scale for Hellige turbidimeter. PMID- 21018409 TI - Chart for determining per cent sludge digestion. PMID- 21018410 TI - Lumbar myelography by abrodil. PMID- 21018411 TI - The roentgenological picture of the coarctation of aorta and its anatomical basis. PMID- 21018412 TI - [Not Available]. PMID- 21018413 TI - The roentgenographic examination of the ankle joint in malleolar fractures. PMID- 21018414 TI - A calcified cyst of the spleen, demonstrated roentgenologically. PMID- 21018415 TI - Studies on A.C. arc lamps. PMID- 21018416 TI - The roentgen appearance of the anterior wall of the sulcus sigmoideus. PMID- 21018417 TI - Percutaneous puncture of renal cysts and tumors. PMID- 21018418 TI - Roentgenologic skeletal changes in myeloma in childhood; platyspondylia generalisata myelomatosa. PMID- 21018419 TI - A case of tibia recurvata. PMID- 21018420 TI - A study of the distribution of radioactive phosphorus in three cases of cancer. PMID- 21018421 TI - On the normal arthrogram of the mandibular joint. PMID- 21018422 TI - Lipoma of the corpus callosum. PMID- 21018423 TI - Newer investigations of radiation effects and their clinical applications. PMID- 21018424 TI - Skeletal and pulmonary metastases from cancer of the kidney, prostate and bladder. PMID- 21018426 TI - Primary mesothelioma (endothelioma) of the pleura. PMID- 21018425 TI - Abdominal lymphogranulomatosis. PMID- 21018427 TI - Unusual urinary calculi. PMID- 21018428 TI - Massive calcification of the liver; case report with a discussion of its etiology on the basis of alveolar hydatid disease. PMID- 21018429 TI - Congenital absence of pedicle from the cervical vertebra. PMID- 21018430 TI - The protection of photofluorographic personnel. PMID- 21018431 TI - The calculation of dose from point and linear sources of radium. PMID- 21018432 TI - TUMORS and tumor metastases in their relation to trauma. PMID- 21018433 TI - Cytological analysis of the response of malignant tumors to irradiation as an approach to a biological basis for dosage in radiotherapy. PMID- 21018434 TI - Nonmalignant conditions of the oesophagus. PMID- 21018435 TI - Broncho-pulmonary dissociation, due to abnormal artery, visualised by bronchography. PMID- 21018436 TI - A case of secondary amoebiasis of the lung. PMID- 21018437 TI - Bite-wing x-rays; a scheme for mass dental radiography. PMID- 21018438 TI - Familial brachydactyly with associated bilateral coxitis. PMID- 21018439 TI - Stereoradiographic viewing by intersection of the optical axes. PMID- 21018440 TI - The evolution of radiography. PMID- 21018441 TI - Time and milliamperes. PMID- 21018442 TI - The roentgenographic signs of herniation of the cervical intervertebral disk. PMID- 21018443 TI - Roentgenographic observations in age; atrophy and osteoporosis of the spine. PMID- 21018444 TI - Reflex hyperemic deossifications regional to joints of the extermities. PMID- 21018445 TI - Non-disabling bronchiectasis. PMID- 21018446 TI - Roentgenograms of the chest in mental deficiency. PMID- 21018447 TI - The roentgenographic appearance of temporomandibular hydrarthrosis. PMID- 21018448 TI - Transient successive pulmonary infiltrations (Loeffler's syndrome). PMID- 21018449 TI - Unusual bone lesions in an infant, probably osteitis tuberculosa multiplex cystoides. PMID- 21018450 TI - Congenital absence of the odontoid process. PMID- 21018451 TI - Congenital absence of the septum pellucidum associated with internal hydrocephalus. PMID- 21018452 TI - March fracture of the articular surface of the tibia and its relation to osteoarthropathy. PMID- 21018453 TI - Fatigue fracture of the metatarsal. PMID- 21018454 TI - Cancer of the skin; a statistical report. PMID- 21018455 TI - Arthrodesis in the treatment of tuberculous coxitis sequelae. PMID- 21018456 TI - On fracture of the carpal scaphoid; a method for operative treatment of inveterate fractures. PMID- 21018457 TI - Herniated nucleus pulposus in a child of twelve years. PMID- 21018458 TI - Tuberculosis of the bones and joints of the foot, including an analysis of the material of the Danish Disablement Pension Board of the years 1921-1940. PMID- 21018459 TI - The treatment of bowleg in rickets. PMID- 21018460 TI - Battle wounds of the thoracic cavity. PMID- 21018461 TI - The wet lung in war casualties. PMID- 21018462 TI - Penetrating wounds of the chest. PMID- 21018463 TI - Thoracic gastric cyst. PMID- 21018464 TI - Results following bands and ligatures on the human internal carotid artery. PMID- 21018465 TI - Gastric retention after posterior gastroenterostomy for duodenal ulcer; prevention and treatment. PMID- 21018467 TI - Postappendicectomy interstitial inguinal hernia. PMID- 21018466 TI - The so-called dumping syndrome after subtotal gastrectomy. PMID- 21018468 TI - Aneurysm of hepatic artery. PMID- 21018469 TI - Reflex vasodilatation in tubed pedicle skin grafts. PMID- 21018470 TI - Rhabdomyosarcoma of the skeletal muscles. PMID- 21018471 TI - Supracondylar amputations; a survey. PMID- 21018472 TI - [Not Available]. PMID- 21018473 TI - [Not Available]. PMID- 21018474 TI - The dangers of modern anaesthesia demand the improved status and remuneration of the anaesthetist. PMID- 21018475 TI - Post-operative pulmonary atelectasis. PMID- 21018476 TI - Epidural analgesia for caesarean section. PMID- 21018477 TI - Preliminary investigation of the use of curare in anaesthetic practice and for treatment of spastic paralysis. PMID- 21018478 TI - The surgery of the thymus gland. PMID- 21018479 TI - Constrictive pericarditis. PMID- 21018480 TI - The last hate; an account of the abdominal injuries of the V-1 and V-2 phases of the war on Britain and of the shelling of Dover. PMID- 21018481 TI - The German hospital centre at Abano Terme. PMID- 21018482 TI - Experimental observations on the use of absorbable and non-absorbable plastics in bone surgery. PMID- 21018484 TI - Penetrating wounds of the chest. PMID- 21018485 TI - Survey of abdominal wounds in 21 Army Group (June, 1944-May, 1945). PMID- 21018483 TI - Interesting cervical tumours; a report of three cases. PMID- 21018486 TI - Spontaneous gangrene of the scrotum (Fournier's gangrene). PMID- 21018487 TI - A case of hindquarter amputation for chondromyxosarcoma of the right thigh. PMID- 21018488 TI - Spontaneous rupture of the spleen in sarcoidosis. PMID- 21018489 TI - The M.E.M. sphygmoscope in vascular injuries. PMID- 21018490 TI - The relative incidence of sternomastoid and ocular torticollis in aircrew recruits. PMID- 21018491 TI - A case of sarcoma of the liver. PMID- 21018492 TI - Rupture of an axillary aneurysm through the quadrilateral space. PMID- 21018493 TI - Fulminating gas gangrene infection following an ischiorectal abscess. PMID- 21018494 TI - Volvulus of the caecum. PMID- 21018495 TI - Chylothorax following traumatic pseudocyst of the pancreas. PMID- 21018496 TI - Tumors of the mediastinum. PMID- 21018497 TI - Resuscitation of the infant. PMID- 21018498 TI - Anesthesia in oral surgery. PMID- 21018499 TI - Anesthesia in ophthalmology. PMID- 21018500 TI - Histologic studies of the brain following head trauma; post-traumatic petechial and massive intracerebral hemorrhage. PMID- 21018501 TI - Treatment of compound spine injuries in forward Army hospitals. PMID- 21018502 TI - Thoracolumbar sympathectomies examined with the electrical skin resistance method. PMID- 21018503 TI - Peripheral nerve surgery; review of incisions for operative exposure; preliminary report. PMID- 21018504 TI - A report on the treatment of craniocerebral wounds in an evacuation hospital. PMID- 21018505 TI - Water content of the brain after concussion and its noncontributory relation to the histopathology of concussion. PMID- 21018506 TI - Treatment of causalgia; an analysis of loo cases. PMID- 21018508 TI - The split mattress bed in the care of spinal cord injuries. PMID- 21018507 TI - A holder for neurosurgical suction tube and cautery. PMID- 21018509 TI - [The healing of post-surgical wounds under conditions of non-specific sensitization of the organism]. PMID- 21018510 TI - [Stimulating action of the epiploon of the newborn transplanted on various wounds]. PMID- 21018511 TI - [On the mechanism of the action of novacaine anesthesia]. PMID- 21018512 TI - [On the changes of certain biochemical indices of the blood and urine in gunshot osteomyelitis]. PMID- 21018513 TI - [Contribution to phantom pains]. PMID- 21018514 TI - [Cutaneous plastics of short imperfect stumps of the shank]. PMID- 21018515 TI - [Concerning the methods of wound heliotherapy]. PMID- 21018516 TI - [Abscesses of the spinal cord]. PMID- 21018517 TI - [Some questions of the surgery of pseudoarticulations]. PMID- 21018518 TI - [Gunshot transdiaphragmal wounds]. PMID- 21018519 TI - [Contribution to the motor function of the small intestine in total resection of the stomach]. PMID- 21018520 TI - [On retrosternal abscesses in gunshot wounds]. PMID- 21018521 TI - [Contribution to the roentgen-diagnosis of purulent arthritis]. PMID- 21018522 TI - [Contribution to roentgenodiagnosis of gas gangrene of the brain]. PMID- 21018523 TI - [Contribution to the diagnosis and treatment of traumatic luxation of the great toe]. PMID- 21018524 TI - [A simple correction of pendant hand in paralysis of the radial nerve]. PMID- 21018525 TI - [The treatment of gunshot wounds of the soft tissues]. PMID- 21018526 TI - [The treatment of slowly closing wounds with concentrated sun rays]. PMID- 21018527 TI - [Fistulography in war traumae]. PMID- 21018528 TI - [Cutaneous-subcutaneous path of metastasis and its resection in surgery for cancer of the thymus gland]. PMID- 21018529 TI - [Surgical technique in the treatment of penetrating lesions of the chest at army regions]. PMID- 21018530 TI - [The treatment of the wounded with open pneumothorax]. PMID- 21018531 TI - [Clinics and therapy of blind injuries of the lungs]. PMID- 21018532 TI - [Injuries of the hand and fingers]. PMID- 21018533 TI - [Gunshot osteomyelitis of the pelvic bones]. PMID- 21018534 TI - [The treatment of gunshot wounds of the articulatio coxae]. PMID- 21018535 TI - [The treatment of gunshot wounds of the femur]. PMID- 21018536 TI - [Osteo-plastic amputation of the shank in tissues known to be infected]. PMID- 21018537 TI - [Development of traumatic osteomyelitis in the roentgen picture]. PMID- 21018539 TI - [Contribution to secondary calculi formation following gunshot wounds of the urinary bladder]. PMID- 21018538 TI - [Observations on certain liver complications in bone fractures]. PMID- 21018540 TI - [Contribution to parapleural abscesses in wounds of the thorax]. PMID- 21018541 TI - [A case of intra vitam discrimination of aneurysm of the aorta abdominalis]. PMID- 21018542 TI - [Spontaneous removal of a rifle-bullet in a case showing gunshot injury of the urinary bladder]. PMID- 21018543 TI - [A case of tearing off of the esophagus in total gastrectomy]. PMID- 21018544 TI - [Modification of the Roux operation for inguinal hernia in the feeble groin]. PMID- 21018545 TI - [A syringe shower]. PMID- 21018546 TI - [On the problem of the surgical restoration of the capacity for work in the disabled of the Patriotic war]. PMID- 21018547 TI - [Not Available]. PMID- 21018548 TI - [Not Available]. PMID- 21018550 TI - [Not Available]. PMID- 21018549 TI - [Not Available]. PMID- 21018551 TI - [Not Available]. PMID- 21018553 TI - [Not Available]. PMID- 21018554 TI - [Not Available]. PMID- 21018552 TI - [Not Available]. PMID- 21018555 TI - [Not Available]. PMID- 21018556 TI - [Not Available]. PMID- 21018557 TI - [Not Available]. PMID- 21018559 TI - [Not Available]. PMID- 21018558 TI - [Not Available]. PMID- 21018560 TI - [Not Available]. PMID- 21018561 TI - [Not Available]. PMID- 21018562 TI - [Not Available]. PMID- 21018563 TI - [Not Available]. PMID- 21018564 TI - [Not Available]. PMID- 21018565 TI - [Not Available]. PMID- 21018567 TI - Adaptability of present day concepts of convalescent training and physical rehabilitation to the civilian practice of medicine. PMID- 21018566 TI - Effects of massage on denervated skeletal muscle. PMID- 21018569 TI - MALPRACTICE: simultaneous application of tight bandaging and heat to arthritic foot [Wisconsin, 1945]. PMID- 21018568 TI - The challenge of crutches; daily activities on crutches. PMID- 21018570 TI - Cervical periarthritis; diagnosis and treatment. PMID- 21018571 TI - Occupations for the sick child. PMID- 21018572 TI - Report on occupational therapy in the Royal Canadian Army Medical Corps hospitals overseas. PMID- 21018573 TI - The treatment of peripheral nerve lesions. PMID- 21018574 TI - The work of a hospital almoner. PMID- 21018575 TI - Some aspects of chronic rheumatism. PMID- 21018576 TI - Equipment aids for the aging person. PMID- 21018577 TI - Marionettes in an Army general hospital. PMID- 21018578 TI - Home workshops. PMID- 21018579 TI - SUGGESTED analysis of pottery as a therapeutic craft for psychiatric patients. PMID- 21018580 TI - International appraisal of research in tropical medicine. PMID- 21018581 TI - Lessons in malariology from World War II. PMID- 21018582 TI - Epidemiology and incubation period of jaundice following yellow fever vaccination. PMID- 21018583 TI - Studies on susceptibility of marsupialia to different strains of yellow fever virus. PMID- 21018584 TI - Bromeliad malaria in Trinidad, British West Indies. PMID- 21018585 TI - Results in an infantry regiment of several plans of treatment for vivax malaria. PMID- 21018586 TI - The diagnosis of schistosomiasis japonica; the symptoms, signs and physical findings characteristic of schistosomiasis japonica at different stages in the development of the disease. PMID- 21018587 TI - The diagnosis of schistosomiasis japonica; the diagnostic characteristics of the eggs of the etiologic agent Schistosoma japonicum. PMID- 21018588 TI - An attempt by feeding to induce in animals reactivity to Trichinella spiralis in the absence of infection. PMID- 21018590 TI - A unitarian view of treponematosis. PMID- 21018589 TI - Detecting intestinal protozoa; saline-iron-hematoxylin solution for wet smears. PMID- 21018591 TI - The influenza epidemic of 1943-1944 in San Antonio, Texas. PMID- 21018592 TI - Foreign quarantine in military traffic. PMID- 21018593 TI - The diamidines; their pharmacological actions and their therapeutic uses in some tropical diseases. PMID- 21018594 TI - The venom of the rhinoceros viper Bitis nasicornis (Shaw). PMID- 21018595 TI - Pyrexia associated with tickbite. PMID- 21018596 TI - [Not Available]. PMID- 21018597 TI - [Not Available]. PMID- 21018598 TI - [Not Available]. PMID- 21018600 TI - [Not Available]. PMID- 21018601 TI - [Not Available]. PMID- 21018599 TI - [Not Available]. PMID- 21018602 TI - [Not Available]. PMID- 21018603 TI - [Not Available]. PMID- 21018604 TI - [Not Available]. PMID- 21018605 TI - [Not Available]. PMID- 21018606 TI - [Not Available]. PMID- 21018607 TI - [Not Available]. PMID- 21018608 TI - [Not Available]. PMID- 21018610 TI - [Not Available]. PMID- 21018609 TI - [Not Available]. PMID- 21018611 TI - [Not Available]. PMID- 21018612 TI - Chest photoroentgenography in Army physical examinations. PMID- 21018613 TI - Miliary tuberculosis of the bone marrow. PMID- 21018614 TI - Pyopneumothorax; treatment of two cases with penicillin. PMID- 21018615 TI - Transcutaneous tuberculin test (Corper). PMID- 21018616 TI - Anatomical studies on human tuberculosis; the reinfection complex. PMID- 21018617 TI - Treatment of experimental ocular tuberculosis with promin. PMID- 21018618 TI - Extrapleural pneumonolysis with paraffin filling. PMID- 21018619 TI - Comments about pneumonectomy and lobectomy in tuberculosis. PMID- 21018620 TI - [Not Available]. PMID- 21018621 TI - [Not Available]. PMID- 21018622 TI - [Not Available]. PMID- 21018623 TI - [Not Available]. PMID- 21018624 TI - [Not Available]. PMID- 21018625 TI - [Not Available]. PMID- 21018626 TI - [Not Available]. PMID- 21018627 TI - [Not Available]. PMID- 21018628 TI - [Not Available]. PMID- 21018629 TI - [Not Available]. PMID- 21018630 TI - [Not Available]. PMID- 21018632 TI - [Not Available]. PMID- 21018631 TI - [Not Available]. PMID- 21018633 TI - [Not Available]. PMID- 21018634 TI - [Not Available]. PMID- 21018636 TI - [Not Available]. PMID- 21018635 TI - [Not Available]. PMID- 21018637 TI - [Not Available]. PMID- 21018638 TI - Thiouracil; an antithyroid drug; an evaluation of its effect in hyperthyroidism. PMID- 21018639 TI - Safe bloodless circumcision of the newborn. PMID- 21018640 TI - A simple and rapid cure of trichomonas vaginitis; preliminary report. PMID- 21018641 TI - In-patient intensive treatment of the syphilitic patient with infectious lesions; the logical step in prophylaxis. PMID- 21018642 TI - Highlights of the Conference in tropical dermatology for American doctors at Mexico City, August 6th-18th, 1945. PMID- 21018643 TI - Treatment of sulfathiazole-resistant-cases of gonorrhea. PMID- 21018644 TI - Cutaneous manifestations of sulfonamides: the drug eruption and Milian's biotropic effect. PMID- 21018645 TI - Topical application of lactic acid in the treatment and prevention of certain disorders of the skin. PMID- 21018646 TI - Effects of penicillin injections on bacterids of the hands and feet. PMID- 21018647 TI - Dermatitis herpetiformis: report of a case with a Koebner-like phenomenon. PMID- 21018648 TI - Venereal disease in the Army Air Forces in the continental United States, 1942 1944. PMID- 21018649 TI - The use of penicillin in the treatment of syphilis of the central nervous system; a report of 100 persons. PMID- 21018650 TI - Seroresistance (Wassermann-fastness) in syphilis; a discussion for the patient. PMID- 21018651 TI - Penicillin therapy of early syphilis in 14,000 patients; follow-up examination of 792 patients six or more months after treatment. PMID- 21018652 TI - Blood and urine arsenic levels of patients with early syphilis under intensive arsenotherapy. PMID- 21018653 TI - The venereal disease problem in a woman's federal reformatory; a study of women released over a period of one year. PMID- 21018654 TI - The problem of reinoculation of human beings with Spirochaeta pallida; a review of the literature. PMID- 21018655 TI - Venereal disease control by New York City Health Department in relation to cooperation with the armed forces. PMID- 21018656 TI - Venereal diseases and workmen's compensation. PMID- 21018657 TI - Social case work among venereally infected females in a quarantine hospital. PMID- 21018658 TI - Factors affecting the response to venereal disease education. PMID- 21018659 TI - Observations on prolapsed rectum in sheep. PMID- 21018660 TI - Urinary calculi associated with vitamin A deficiency in the fox. PMID- 21018661 TI - A comparison of carotene and vitamin A utilization by the fox. PMID- 21018662 TI - Changes of the blood constituents in diseases of ruminants. PMID- 21018663 TI - A histopathological study of depigmented irises from single comb white leghorns. PMID- 21018664 TI - Immunization against a lymphoid tumor of the chicken; attenuation by heat, drying and chemicals. PMID- 21018665 TI - Ten per cent cunic for controlling gastro-intestinal helminthiasis in sheep. PMID- 21018666 TI - The lymphatic circulation of the hind limbs of the horse. PMID- 21018667 TI - Experiments in the use of sulfathiazole for turkeys. PMID- 21018668 TI - The value of vitamin A therapy in cases diagnosed as ketosis in dairy cows. PMID- 21018669 TI - Ticks found in New York State. PMID- 21018670 TI - Value of DDT for the control of the northern feather mite. PMID- 21018671 TI - Diaphragmatic hernia in the bovine; case report. PMID- 21018672 TI - The oculo-gyral illusion; a form of apparent motion which may be observed following stimulation of the semicircular canals. PMID- 21018673 TI - Altitude pain; a study of individual differences in susceptibility to bends, chokes, and related symptoms. PMID- 21018674 TI - The effects of cold and rate of ascent on aeroembolism. PMID- 21018675 TI - Incidence of bends pain in a short exposure to simulated altitudes of 26,000, 28,000 and 30,000 feet. PMID- 21018676 TI - A study of the brain after intermittent exposure to a simulated altitude of 23,000 feet. PMID- 21018677 TI - The relationship of air sickness to other types of motion sickness. PMID- 21018678 TI - Environmental temperature and swing sickness. PMID- 21018679 TI - Occurrence of decompression sickness on descent from high altitudes. PMID- 21018681 TI - Physical fitness and age of Army Air Forces personnel. PMID- 21018680 TI - Safety and aircraft design. PMID- 21018682 TI - Human factors in the visual examination of aviators. PMID- 21018683 TI - Scientific medicine in aviation. PMID- 21018684 TI - The nutrition of phytopathogenic bacteria; minimal nutritive requirements of the genus Xanthomonas. PMID- 21018685 TI - The in vitro action of sulfonamides and penicillin on Actinomyces. PMID- 21018686 TI - Electrokinetic studies on bacterial surfaces; the effects of surface-active agents on the electrophoratic mobilities of bacteria. PMID- 21018687 TI - The antigenic complex of Shigella paradysenteriae, Boyd type P274. PMID- 21018688 TI - Further observations on the nuclear material of the bacterial cell. PMID- 21018689 TI - The action of penicillin on Staphylococcus. PMID- 21018690 TI - On the process of sporulation in a strain of Bacillus cereus. PMID- 21018691 TI - The action of penicillin on several genera of the Actinomycetales. PMID- 21018692 TI - A method for restoring and maintaining the phenol resistance of certain strains of Staphylococcus aureus. PMID- 21018693 TI - Further notes on variation in certain saprophytic actinomycetes. PMID- 21018694 TI - A study of the dissociative behavior of Pseudomonas aeruginosa. PMID- 21018695 TI - Observations on strains of a monophasic Salmonella variant. PMID- 21018696 TI - A method for differentiating Candida albicans in tissue. PMID- 21018697 TI - A method for the preparation of complement-fixing antigens in a study of experimental Tsutsugamushi disease (scrub typhus). PMID- 21018698 TI - The comparative sensitivity of Venezuelan equine encephalomyelitis virus neutralization tests in chick embryos and in mice. PMID- 21018699 TI - A note on pH tolerance of Aerobacter aerogenes and Aerobacillus macerans as related to natural ecology and decomposition of acid food products. PMID- 21018700 TI - Note on the production of soluble blue pigment in simple media by Actinomyces coelicolor. PMID- 21018701 TI - The anaerobic bacterial flora of clostridial myositis. PMID- 21018702 TI - The occurrence of type 10 paracolon in turkeys. PMID- 21018703 TI - The isolation of Sarcina ureae (Beijerinck) Lohnis from sea water. PMID- 21018704 TI - The stability of penicillin in aqueous solution. PMID- 21018705 TI - The mode of action of nitrofuran compounds; action versus Staphylococcus aureus. PMID- 21018706 TI - Soil enrichment and development of antagonistic microorganisms. PMID- 21018707 TI - The mannitol-negative Shigella group. PMID- 21018708 TI - Dissociation in Brucella abortus; a demonstration of the role of inherent and environmental factors in bacterial variation. PMID- 21018709 TI - Studies on bacterial mutability; the time of appearance of the mutant in Escherichia coli. PMID- 21018710 TI - Bacillin, a new antibiotic substance from a soil isolate of Bacillus subtilis. PMID- 21018711 TI - Antibacillin, a naturally occurring inhibitor of bacillin. PMID- 21018712 TI - A growth factor in certain vegetable juices. PMID- 21018713 TI - Metabolic changes in submerged penicillin fermentations on synthetic media. PMID- 21018714 TI - The effect of desiccation on the activity and moisture content of bakers' yeast. PMID- 21018715 TI - Paracolon type 10 from captive rattlesnakes. PMID- 21018716 TI - An observation of apparent substitution of pantothenate by thiamine and choline. PMID- 21018717 TI - [Not Available]. PMID- 21018718 TI - Factors affecting carcinogenesis; the effect of hydrogenation of lipid solvents on carcinogenesis by 3,4-benzpyrene. PMID- 21018719 TI - Factors affecting carcinogenesis; the effect of tricaprylin solutions of cholesterol and phospholipins. PMID- 21018720 TI - Influence of age on total epidermal lipid during carcinogenesis induced by methylcholanthrene in mice. PMID- 21018721 TI - Action of methylcholanthrene on certain scars of the skin in mice. PMID- 21018722 TI - A filtrable agent producing lymphoid tumors and osteopetrosis in chickens. PMID- 21018723 TI - Ocular tumors with exophthalmia in xiphophorin fishes. PMID- 21018724 TI - The treatment of malignant tumors by bacterial toxins as developed by the late William B. Coley, M.D., reviewed in the light of modern research. PMID- 21018725 TI - Degradation of cystine peptides by tissues; dehydropeptidase activity in normal and neoplastic tissues. PMID- 21018726 TI - Enzymatic hydrolysis of benzoylarginineamide in normal and neoplastic tissues. PMID- 21018727 TI - Note on some aspects of the effect of nucleates in primary and transplanted rat hepatomas. PMID- 21018728 TI - Enzymatic activity in primary and transplanted rat hepatomas. PMID- 21018729 TI - Protective effect of thymus nucleate on the heat coagulation of proteins. PMID- 21018730 TI - Quantitative studies on the latent period of tumors induced with subcutaneous injections of the agent of chicken tumor I; curve relating dosage of agent and chicken response. PMID- 21018731 TI - A study of the subjective sensations associated with extrasystoles. PMID- 21018732 TI - Treatment of coronary disease with angina by pericoronary neurectomy combined with ligation of the great cardiac vein; a case report. PMID- 21018733 TI - Paroxysmal pulmonary edema consequent to stimulation of cardiovascular receptors; effect of intraarterial and intravenous infusions. PMID- 21018734 TI - Paroxysmal pulmonary edema consequent to stimulation of cardiovascular receptors; mechanical and neurogenic elements. PMID- 21018735 TI - Paroxysmal pulmonary edema consequent to stimulation of cardiovascular receptors; pharmacologic experiments. PMID- 21018736 TI - The coincidence of auricular fibrillation and bacterial endocarditis. PMID- 21018737 TI - Pathologic study of thirty-one cases of scrub typhus fever with especial reference to the cardiovascular system. PMID- 21018738 TI - An analysis of the time relationships within the cardiac cycle in electrocardiograms of normal men. The duration of the Q-T interval and its relationship to the cycle length (R-R interval). PMID- 21018739 TI - The peripheral blood flow under basal conditions in older male subjects with normal and elevated blood pressures. PMID- 21018740 TI - Interatrial and sinoatrial block, with an illustrative case. PMID- 21018741 TI - Spontaneous mediastinal emphysema; a case report demonstrating electrocardiographic changes. PMID- 21018742 TI - Pure congenital pulmonary stenosis; case report. PMID- 21018743 TI - Myxoma of heart. PMID- 21018744 TI - The alkaloids of Lycopodium species; Lycopodium lucidulum Michx. (Urostachys lucidulus Herter). PMID- 21018746 TI - The alkaloids of fumariaceous plants; Corydalis cornuta Royle. PMID- 21018745 TI - The alkaloids of Lycopodium species; Lycopodium sabinaefolium Willd. PMID- 21018747 TI - Comparative tolerance to mixtures of natural and racemic amino acids on intravenous infusion in the dog. PMID- 21018748 TI - The effect of protein on the nicotinic acid and tryptophane requirement of the growing rat. PMID- 21018749 TI - The isolation and identification of a natural precursor of choline. PMID- 21018750 TI - The determination of inorganic phosphate in the presence of labile phosphate esters. PMID- 21018751 TI - A homomolecular serum protein with anomalous solubilities. PMID- 21018752 TI - Synthesis of cholesterol in surviving liver. PMID- 21018753 TI - Biochemical transformations as determined by competitive analogue-metabolite growth inhibitions; some transformations involving aspartic acid. PMID- 21018754 TI - Biochemical transformations as determined by competitive analogue-metabolite growth inhibitions; some transformations involving p-aminobenzoic acid. PMID- 21018755 TI - Changes that occur in plasma proteins during growth of the dog. PMID- 21018756 TI - A study of the requirements of white leghorn chicks for new and unidentified members of the vitamin B complex. PMID- 21018757 TI - Partial synthesis of compounds related to adrenal cortical hormones; the structure of Delta 11-lithocholenic acid. PMID- 21018758 TI - Partial synthesis of compounds related to adrenal cortical hormones; some reactions of an epoxide of Delta 11-lithocholenic acid. PMID- 21018759 TI - Partial synthesis of compounds related to adrenal cortical hormones; preparation of 3 (alpha), 11 (alpha)-dihydroxycholanic acid. PMID- 21018760 TI - Partial synthesis of compounds related to adrenal cortical hormones; an improved method for the preparation of 3 (alpha), 11 (alpha)-dihydroxycholanic acid. PMID- 21018761 TI - Partial synthesis of compounds related to adrenal cortical hormones; preparation of 3 (alpha), 11 (alpha)-dihydroxy-12-ketocholanic acid and the products obtained by Wolff-Kishner reduction. PMID- 21018762 TI - Partial synthesis of compounds related to adrenal cortical hormones; the structure of the 3 (alpha), 11-dihydroxy-12-ketocholanic acid of Marker and Lawson and of the products obtained by Wolff-Kishner reduction. PMID- 21018763 TI - Partial synthesis of compounds related to adrenal cortical hormones; degradation of the side chain of cholanic acid. PMID- 21018764 TI - Steroids derived from bile acids; the preparation of 3 (alpha)-hydroxy-Delta 11 cholenic acid from desoxycholic acid. PMID- 21018765 TI - Steroids derived from bile acids; 3 (alpha)-hydroxy-11,12-dibromocholanic acid and related compounds. PMID- 21018766 TI - Steroids derived from bile acids; derivatives of Delta 9,11-cholenic acid with substituents at C3 and C12. PMID- 21018767 TI - The introduction of an 11-hydroxyl group in 12-ketosteroids. PMID- 21018768 TI - The structure of some derivatives of 3 (alpha)-hydroxy-Delta 9,11-cholenic acid. PMID- 21018769 TI - Partial synthesis of pregnene-4-triol-17(beta), 20(beta), 21-dione-3,11 and pregnene-4-diol-17(beta), 21-trione-3,11,20 monoacetate. PMID- 21018770 TI - Improved methods for the preparation of 3 (alpha)-hydroxy-Delta 9,11-cholenic acid. PMID- 21018771 TI - The introduction of oxygen into the steroid nucleus at the C11 position. PMID- 21018772 TI - Studies on the preparation and rearrangement of certain steroid oxides. PMID- 21018773 TI - Experimental studies in the steroids; the oxidation of methyl 3(alpha)-acetoxy-11 keto-12-bromocholanate. PMID- 21018774 TI - Experimental investigations in the chemistry of ring C in desoxycholic acid. PMID- 21018775 TI - Experimental studies in the steroids; a novel method for the preparation of sterol dichlorides. PMID- 21018776 TI - The bromine degradation of the silver salts of bile acids and related compounds. PMID- 21018777 TI - The Wolff-Kishner reduction of 3(alpha), 12-dihydroxy-11-ketocholanic acid. PMID- 21018778 TI - The Wolff-Kishner reduction of 3(alpha)-hydroxy-11,12-diketocholanic acid. PMID- 21018779 TI - Attempts to find new antimalarials; amino alcohols derived from phenanthrene and tetrahydrophenanthrene. PMID- 21018780 TI - 9-alkylamino carbinols derived from 9-acyl-1,2,3,4-tetrahydrophenanthrene derivatives. PMID- 21018781 TI - 7-methoxy-8-acetyl- and 7-methoxy-9-acetyl-1,2,3,4-tetrahydrophenanthrene and amino carbinols derived from them. PMID- 21018782 TI - 7-chloro- and 7-methoxy-8-chloro-1,2,3,4-tetrahydrophenanthrene and amino carbinols derived from them. PMID- 21018783 TI - Substituted alpha-dialkylaminoalkyl-1-naphthalenemethanols; reduction of substituted naphthyl halomethyl ketones to halohydrins; derived amino alcohols. PMID- 21018784 TI - Substituted alpha-dialkylaminoalkyl-1-naphthalenemethanols; substituted alpha naphthylethylene oxides and derived amino alcohols. PMID- 21018785 TI - Substituted alpha-dialkylaminoalkyl-1-naphthalenemethanols; the preparation of some alpha-dialkylaminomethyl-2-chloro- and bromo-1-naphthalenemethanols. PMID- 21018786 TI - Derivatives of 6-methoxy-8-nitroquinoline; chlorination with sulfuryl chloride. PMID- 21018787 TI - Attempts to find new antimalarials; studies in the acridine series; 9-N heterocyclic acridines and 9-acridylsulfanilamides. PMID- 21018788 TI - Attempts to find new antimalarials; some heterocyclic sulfanilamide derivatives. PMID- 21018789 TI - Arylsulfonyl esters of nitro alcohols. PMID- 21018790 TI - 2-phenylindole-3-aldehyde and certain of its condensation products. PMID- 21018791 TI - The chemistry of citrinin; the synthesis of 2,4-dimethoxy-3-ethylbenzoic acid, and 2,6-dimethoxy-3-methylbenzoic acid. PMID- 21018792 TI - Alkylation of ethyl malonate with diethoxymethyl acetate. PMID- 21018793 TI - Dimorphism of high molecular weight symmetrical normal aliphatic secondary amines. PMID- 21018794 TI - Blood and blood derivatives; a new public health field. PMID- 21018795 TI - Some normal values for the blood chemistry of healthy, normal, young adult males. PMID- 21018796 TI - Intravenous therapy. PMID- 21018797 TI - The total solids, fat and nitrogen in the feces; a study of normal persons and of patients with duodenal ulcer on a test diet containing large amounts of fat. PMID- 21018798 TI - The total solids, fat and nitrogen in the feces; a study of persons who had undergone partial gastrectomy with anastomosis of the entire cut end of the stomach and the jejunum (polya anastomosis). PMID- 21018799 TI - A gastroscopic study following an outbreak of food poisoning. PMID- 21018800 TI - A review of the literature on roentgenology of the gastrointestinal tract for the year 1944. PMID- 21018801 TI - Curling's ulcer in experimental burns; the effect of penicillin therapy. PMID- 21018802 TI - The frequency of peptic ulcers in protein-deficient dogs. PMID- 21018803 TI - An attempt to prevent histamine-induced ulcers in dogs by the administration of enterogastrone concentrates. PMID- 21018804 TI - ARE present-day standards of nutrition satisfactory? PMID- 21018805 TI - Abdominal pain from the surgeon's point of view. PMID- 21018806 TI - Hydrops of the gallbladder. PMID- 21018807 TI - Gastric mucosa in infectious hepatitis; roentgenologic and gastroscopic studies; report on ten cases. PMID- 21018808 TI - Gastroscopy. PMID- 21018809 TI - [Not Available]. PMID- 21018810 TI - [Not Available]. PMID- 21018811 TI - [Not Available]. PMID- 21018812 TI - [Not Available]. PMID- 21018813 TI - The enhancement of circulating antibody concentration by adrenal cortical hormones. PMID- 21018814 TI - A comparison of rabbit and mouse antisera to Shigella paradysenteriae. PMID- 21018815 TI - Studies on bacterial viruses. PMID- 21018816 TI - Observations on the mode of action of acridines in inhibiting lysis of virus infected bacteria. PMID- 21018817 TI - Changes of the serum phosphatase level after infection of cows with Brucella abortus. PMID- 21018818 TI - Experimental exposure of human subjects to viruses of influenza. PMID- 21018819 TI - Shigella paradysenteriae (Flexner) type II. VII. PMID- 21018820 TI - Propagation of Japanese B encephalitis virus in the developing chick embryo. PMID- 21018821 TI - Weil-Felix and typhus complement-fixation tests in relapsing fever, with special reference to B. proteus OX-K agglutination. PMID- 21018822 TI - The effects of immunization with histamine azoprotein on histamine-intoxication and passive anaphylaxis in the guinea-pig. PMID- 21018823 TI - The specific polysaccharides of types A, B, C, D and F Hemophilus influenzae. PMID- 21018824 TI - The phase variation of Shigella paradysenteriae (Flexner) type IV. PMID- 21018825 TI - The duration of antibody-formation after injection of killed typhoid bacilli in water-in-oil emulsion. PMID- 21018826 TI - Antigenic relationships of the West Nile, Japanese B encephalitis, and St. Louis encephalitis viruses. PMID- 21018827 TI - Quantitative studies on the neutralization of pathogenic agents in tissues by circulating antibodies; the Ai values and the avidities of tetanal toxins for nerve tissue and antitoxin. PMID- 21018828 TI - The immunochemistry of allergens; precipitin formation and passive transfer reactions with allergenic proteins from cottonseed and castor beans. PMID- 21018829 TI - The relationship of the protein-reserves to antibody-production; the influence of protein repletion upon the production of antibody in hypoproteinemic adult white rats. PMID- 21018830 TI - The action of penicillin on staphylococci. PMID- 21018831 TI - The expanding field of physical medicine. PMID- 21018833 TI - Vocational rehabilitation in the postwar period. PMID- 21018832 TI - Rehabilitation and the industrial worker. PMID- 21018834 TI - Six traffic signals in the rehabilitation of the tuberculous. PMID- 21018835 TI - The psychiatric aspects of the vocational rehabilitation program. PMID- 21018836 TI - Speech rehabilitation. PMID- 21018837 TI - TYPHUS situation in Europe. PMID- 21018838 TI - [Not Available]. PMID- 21018839 TI - [Not Available]. PMID- 21018840 TI - [Not Available]. PMID- 21018841 TI - The painful stiff shoulder (frozen shoulder). PMID- 21018842 TI - Protracted insulin coma in treatment of psychoses. PMID- 21018843 TI - Reticulum cell sarcoma; reticulum cell sarcoma of the frontal sinus. PMID- 21018845 TI - Amyloidosis myocardii. PMID- 21018844 TI - Lipoma of the sigmoid which appeared four years after resection of an adenocarcinoma of the transverse colon. PMID- 21018846 TI - Pathogenetic studies on lupus erythematosus disseminatus and related diseases. PMID- 21018847 TI - Concerning the effect of frequency and of age on the QRS time of electrocardiogram. PMID- 21018848 TI - Tuberculin negative erythema nodosum. PMID- 21018849 TI - The bilirubin production of the human organism and its significance to the pathogenesis of jaundice. PMID- 21018850 TI - On the results of the medical treatment of peptic ulcer. PMID- 21018851 TI - [Not Available]. PMID- 21018852 TI - [Not Available]. PMID- 21018853 TI - [Not Available]. PMID- 21018854 TI - [Not Available]. PMID- 21018855 TI - [Not Available]. PMID- 21018856 TI - [Not Available]. PMID- 21018857 TI - [Not Available]. PMID- 21018858 TI - [Not Available]. PMID- 21018859 TI - Penicillin treatment of empyema; report of 24 cases and review of the literature. PMID- 21018860 TI - Quinidine in the treatment of auricular fibrillation in association with congestive failure. PMID- 21018861 TI - Blastomycosis; a brief review of the literature and a report of a case involving the meninges. PMID- 21018862 TI - The clinical and roentgenologic diagnosis of pericardial effusion. PMID- 21018863 TI - Studies on sensitivity of diphtheria to penicillin. PMID- 21018864 TI - Periarteritis nodosa; a clinocopathological analysis of seven cases. PMID- 21018865 TI - An analysis of complications encountered during therapeutic malaria. PMID- 21018866 TI - The response of cirrhosis of the liver to an intensive combined therapy. PMID- 21018867 TI - Acute bacterial endocarditis; a case report with recovery after treatment with penicillin. PMID- 21018868 TI - Subacute bacterial endocarditis, Streptococcus viridans, with mensenteric thrombosis and recovery. PMID- 21018870 TI - Ectodermosis erosiva pluri-orificialis (Klauder's syndrome). PMID- 21018869 TI - Hyperinsulinism of an unusual type; a metabolic study. PMID- 21018871 TI - A case of atrophic tracheobronchitis with metaplasia. PMID- 21018872 TI - HEPATITIS. PMID- 21018873 TI - [Not Available]. PMID- 21018874 TI - [Not Available]. PMID- 21018875 TI - [Not Available]. PMID- 21018876 TI - [Not Available]. PMID- 21018877 TI - [Not Available]. PMID- 21018878 TI - [Not Available]. PMID- 21018879 TI - Streptococcic and nonstreptococcic disease of the respiratory tract; epidemiologic observations. PMID- 21018880 TI - Progressive bilateral bullous emphysema. PMID- 21018881 TI - Fulminating meningococcemia with vascular collapse (Waterhouse-Friderichsen syndrome); report on four adult patients who recovered. PMID- 21018882 TI - Atypical hemolytic anemia; observations with particular reference to the use of transfusions in the study of hemolytic mechanisms. PMID- 21018883 TI - Absorption, distribution and excretion of streptomycin. PMID- 21018884 TI - [Not Available]. PMID- 21018885 TI - [Not Available]. PMID- 21018886 TI - [Not Available]. PMID- 21018887 TI - [Not Available]. PMID- 21018888 TI - [Not Available]. PMID- 21018889 TI - [Not Available]. PMID- 21018890 TI - [Not Available]. PMID- 21018891 TI - [Not Available]. PMID- 21018892 TI - [Not Available]. PMID- 21018893 TI - [Not Available]. PMID- 21018895 TI - [Not Available]. PMID- 21018894 TI - [Not Available]. PMID- 21018896 TI - [Not Available]. PMID- 21018897 TI - [Not Available]. PMID- 21018898 TI - [Not Available]. PMID- 21018899 TI - [Not Available]. PMID- 21018900 TI - [Not Available]. PMID- 21018901 TI - [Not Available]. PMID- 21018902 TI - [Not Available]. PMID- 21018903 TI - The health problem in Berlin (July, 1945, to January, 1946). PMID- 21018904 TI - Nutrition of school-children in Leeds, winter, 1943, and summer, 1944. PMID- 21018905 TI - Unusual gunshot wound of the internal carotid artery. PMID- 21018907 TI - Hypertension in ruptured kidney. PMID- 21018906 TI - Congenital malaria. PMID- 21018908 TI - Sigmoidoscopy; perforation of the rectum. PMID- 21018909 TI - Penicillin in otitic meningitis. PMID- 21018910 TI - India and birth control. PMID- 21018911 TI - Homosexuality. PMID- 21018912 TI - [Not Available]. PMID- 21018913 TI - [Not Available]. PMID- 21018914 TI - [Not Available]. PMID- 21018915 TI - [Not Available]. PMID- 21018916 TI - [Not Available]. PMID- 21018917 TI - [Not Available]. PMID- 21018918 TI - [Not Available]. PMID- 21018919 TI - [Not Available]. PMID- 21018921 TI - [Not Available]. PMID- 21018920 TI - [Not Available]. PMID- 21018922 TI - [Not Available]. PMID- 21018923 TI - [Not Available]. PMID- 21018924 TI - [Not Available]. PMID- 21018925 TI - [Not Available]. PMID- 21018926 TI - [Not Available]. PMID- 21018927 TI - Neurosurgical conditions in general practice. PMID- 21018928 TI - A protective cabinet for investigators studying Coccidioides immitis and other infectious fungi. PMID- 21018930 TI - Early filariasis. PMID- 21018929 TI - Enzymatic oxidations in tissue fractions of the ciliary processes. PMID- 21018931 TI - [Not Available]. PMID- 21018932 TI - [Not Available]. PMID- 21018933 TI - [Not Available]. PMID- 21018934 TI - [Not Available]. PMID- 21018935 TI - [Not Available]. PMID- 21018936 TI - [Not Available]. PMID- 21018937 TI - Studies on experimental motion sickness. PMID- 21018938 TI - Staphylocoagulase and related substances. PMID- 21018939 TI - The early diagnosis of coronary heart disease. PMID- 21018940 TI - Obstetric trends during the last five years. PMID- 21018942 TI - Army urological problems. PMID- 21018941 TI - Slipping epiphysis of head of femur in growing children. PMID- 21018943 TI - The diagnosis of myxedema. PMID- 21018944 TI - Thrombosis and embolism; a preliminary report on the comparative results of femoral vein interruption and dicumarol therapy. PMID- 21018946 TI - Infectious hepatitis. PMID- 21018945 TI - Sedation as a technique in psychotherapy. PMID- 21018947 TI - The eye as a guide to latent nutritional deficiency diseases; a clinical study of ocular diseases at an advanced base hospital in the Southwest Pacific. PMID- 21018948 TI - Research on breast cancer. PMID- 21018949 TI - Pathology of cancer of the breast. PMID- 21018950 TI - Surgery of cancer of the breast. PMID- 21018951 TI - Radiological treatment of carcinoma of the breast. PMID- 21018952 TI - Dietary control of renal hypertension. PMID- 21018953 TI - Typhoid fever outbreak traced to cream filled pastries. PMID- 21018955 TI - Deafness; a modern approach to its treatment. PMID- 21018954 TI - Corneal transplantation; report of case. PMID- 21018956 TI - Congenital atresia of the esophagus with tracheo-esophageal fistula. PMID- 21018957 TI - Calcified true aneurism of left renal artery. PMID- 21018958 TI - Treatment of experimental motion sickness in humans. PMID- 21018959 TI - The effect of riboflavin deficiency on renal damage due to sulphanilyl guanidine in the albino rat. PMID- 21018960 TI - A comparison of the efficacy of different infusion media in shock. PMID- 21018961 TI - The neurogenic bladder in spinal cord injury. PMID- 21018962 TI - Volkmann's ischaemic contracture. PMID- 21018963 TI - Functional uterine bleeding. PMID- 21018964 TI - A survey of the ophthalmic status of the Cree Indians at Norway House, Manitoba. PMID- 21018965 TI - Hypertension and its management. PMID- 21018966 TI - [Not Available]. PMID- 21018967 TI - Immunization against pertussis with endotoxoid vaccine. PMID- 21018968 TI - Maternal and fetal anoxia. PMID- 21018970 TI - Toward a lower mortality in appendicitis. PMID- 21018969 TI - Continuous spinal or lumbar anaesthesia. PMID- 21018971 TI - The diagnosis and treatment of the ocular muscle anomalies. PMID- 21018972 TI - Osteomyelitis of the frontal bone with brain abscess. PMID- 21018973 TI - Paraesthesias of upper extremity; treatment by stellate ganglion block. PMID- 21018974 TI - Cerebral anoxia complicating spinal anaesthesia. PMID- 21018975 TI - Scurvy in a Cree Indian. PMID- 21018976 TI - Irresistible impulse and crime. PMID- 21018977 TI - Cellona technique in preparing moulages. PMID- 21018978 TI - Southern Alberta medicine in the 'eighties. PMID- 21018979 TI - The treatment of pernicious anemia. PMID- 21018980 TI - Present status of the surgical treatment of hyperthyroidism. PMID- 21018981 TI - Present status of thiouracil. PMID- 21018982 TI - Typhoid shock therapy; results of 15 years' experience. PMID- 21018983 TI - The use of tantalum for repair of cranial defects in infected cases. PMID- 21018984 TI - Sulfadiazine anuria; report of a case. PMID- 21018985 TI - Surgical treatment of intractable plantar warts. PMID- 21018986 TI - Parenteral fluid therapy; a general consideration. PMID- 21018987 TI - Beta radiation in ophthalmology. PMID- 21018988 TI - Treatment of carcinoma of the prostate. PMID- 21018989 TI - SULFONAMIDE therapy in acute diarrheal disorders. PMID- 21018990 TI - PENICILLIN in infectious diseases of childhood. PMID- 21018991 TI - SCHISTOSOMIASIS (bilharziasis); possibility of its occurrence in discharged veterans. PMID- 21018992 TI - On the significance of nutritional deficiency in diabetes. PMID- 21018993 TI - Treatment of ichthyosis. PMID- 21018995 TI - [Not Available]. PMID- 21018994 TI - [Not Available]. PMID- 21018996 TI - [Not Available]. PMID- 21018997 TI - [Not Available]. PMID- 21018998 TI - Recent advances in therapeutics. PMID- 21018999 TI - Pains in the legs in children. PMID- 21019000 TI - A case of anuria. PMID- 21019001 TI - Genito-urinary calculi. PMID- 21019003 TI - Appendicitis in the newborn. PMID- 21019002 TI - Low blood pressure. PMID- 21019004 TI - [Not Available]. PMID- 21019005 TI - [Not Available]. PMID- 21019006 TI - [Not Available]. PMID- 21019007 TI - [Not Available]. PMID- 21019008 TI - [Not Available]. PMID- 21019009 TI - [Not Available]. PMID- 21019010 TI - [Not Available]. PMID- 21019011 TI - [Not Available]. PMID- 21019012 TI - [Not Available]. PMID- 21019013 TI - Management of peptic ulcers with a high protein, high caloric diet. PMID- 21019015 TI - What the Farm Bureau expects from medicine. PMID- 21019016 TI - What industry expects of medicine. PMID- 21019014 TI - Potentialities of group practice of medicine. PMID- 21019017 TI - What labor expects from medicine. PMID- 21019018 TI - Valvular heart disease (rheumatic) in rejectees; survey of 100,000 cardiac examinations performed at the New Haven Recruiting and Induction Station, New Haven, Connecticut. PMID- 21019019 TI - The medical aspects of the Candlewood Lake murder. PMID- 21019020 TI - The semi-centennial of Roentgen's discovery. PMID- 21019021 TI - The pharmacological therapeutic aspects of migraine. PMID- 21019022 TI - Malaria. PMID- 21019024 TI - Problems of rehabilitation in patients with cerebral palsy. PMID- 21019023 TI - Early determination of gall bladder disease and its treatment. PMID- 21019025 TI - Healed dissecting aneurysm of the aorta, with signs of aortic insufficiency; case report. PMID- 21019026 TI - [Not Available]. PMID- 21019027 TI - [Not Available]. PMID- 21019028 TI - [Not Available]. PMID- 21019029 TI - [Not Available]. PMID- 21019030 TI - [Not Available]. PMID- 21019031 TI - [Not Available]. PMID- 21019032 TI - [Not Available]. PMID- 21019033 TI - [Not Available]. PMID- 21019034 TI - [Not Available]. PMID- 21019035 TI - [Not Available]. PMID- 21019036 TI - [Not Available]. PMID- 21019037 TI - [Not Available]. PMID- 21019038 TI - [Not Available]. PMID- 21019039 TI - [Not Available]. PMID- 21019040 TI - [Not Available]. PMID- 21019041 TI - [Not Available]. PMID- 21019042 TI - [Not Available]. PMID- 21019043 TI - [Not Available]. PMID- 21019044 TI - [Not Available]. PMID- 21019045 TI - [Not Available]. PMID- 21019046 TI - [Not Available]. PMID- 21019047 TI - [Not Available]. PMID- 21019048 TI - [Not Available]. PMID- 21019049 TI - [Not Available]. PMID- 21019050 TI - Malnutrition in Africans as an indication of their dietary requirements. PMID- 21019051 TI - Diabetes insipidus and obesity in an Itesot leper child. PMID- 21019052 TI - The Cooke-Ponder lobular neutrophil count on the East African Askari. PMID- 21019053 TI - The use of 666 in the control of Ornithodoros moubata, Murray. PMID- 21019054 TI - Penicillin in treatment of relapsing fever. PMID- 21019055 TI - Increasing incidence of pulmonary tuberculosis in children in Glasgow. PMID- 21019056 TI - Some experiences in mass radiography. PMID- 21019057 TI - The pathogenesis of tuberculous epididymitis. PMID- 21019058 TI - Symposium on tuberculosis nursing. PMID- 21019059 TI - Acute inflammation and abscess formation due to a diphtheroid bacillus. PMID- 21019060 TI - [Not Available]. PMID- 21019061 TI - [Not Available]. PMID- 21019062 TI - [Not Available]. PMID- 21019063 TI - [Not Available]. PMID- 21019064 TI - Equipment for the calling of medicine. PMID- 21019065 TI - The radiological investigation of tumours of the colon. PMID- 21019066 TI - Henoch-Schonlein purpura and acute nephritis due to food allergy. PMID- 21019067 TI - [Not Available]. PMID- 21019068 TI - [Not Available]. PMID- 21019069 TI - [Not Available]. PMID- 21019071 TI - [Not Available]. PMID- 21019070 TI - [Not Available]. PMID- 21019072 TI - [Not Available]. PMID- 21019073 TI - Glaucoma. PMID- 21019074 TI - [Not Available]. PMID- 21019075 TI - [Not Available]. PMID- 21019076 TI - [Not Available]. PMID- 21019077 TI - [Not Available]. PMID- 21019078 TI - [Not Available]. PMID- 21019079 TI - [Not Available]. PMID- 21019080 TI - [Not Available]. PMID- 21019081 TI - [Not Available]. PMID- 21019082 TI - [Not Available]. PMID- 21019083 TI - [Not Available]. PMID- 21019084 TI - Hypoglycemia. PMID- 21019085 TI - Surgical results with parenteral nutrition. PMID- 21019086 TI - Treatment of infections with penicillin given orally. PMID- 21019087 TI - Early diagnosis of cancer of the uterus. PMID- 21019088 TI - Diagnosis and treatment of hypothyroidism in children. PMID- 21019089 TI - Urgent needs in psychiatric medicine. PMID- 21019090 TI - Hydrotherapy. PMID- 21019091 TI - Transurethral prostatectomy; with analysis of end results. PMID- 21019092 TI - Anesthesiology in the hospital and in the medical school. PMID- 21019093 TI - Early calcium urolithiasis. PMID- 21019094 TI - The remaining task. PMID- 21019095 TI - Medical education in Europe. PMID- 21019096 TI - Perineal prostatectomy under continuous caudal anesthesia. PMID- 21019097 TI - Selection of hypertensive patients for sympathectomy. PMID- 21019098 TI - The clinical use of oral basal temperatures. PMID- 21019100 TI - Severe burns from inflammable cowboy pants. PMID- 21019099 TI - Mycotic meningitis due to Candida. PMID- 21019102 TI - MALPRACTICE: limitation of action; false certification of insanity. PMID- 21019101 TI - Brucella melitensis isolated from swine tissues in Iowa. PMID- 21019103 TI - Medical progress and medical education during the war. PMID- 21019104 TI - Procaine intravenously in treatment of delayed serum sickness. PMID- 21019105 TI - Health of repatriated prisoners of war from the Far East. PMID- 21019106 TI - The fenestration operation for otosclerosis. PMID- 21019107 TI - Bronchogenic carcinoma; diagnosis by cytologic study of bronchoscopically removed secretions. PMID- 21019108 TI - Toxic phenobarbital reaction complicating myocardial infarction. PMID- 21019110 TI - Development of high educational standards by the medical profession. PMID- 21019109 TI - Sulfanilamide spray for pain in tuberculous laryngitis. PMID- 21019111 TI - Reactions in penicillin therapy. PMID- 21019112 TI - Urinary incontinence in female from ectopic ureteral orifices. PMID- 21019113 TI - Melioidosis on Guam. PMID- 21019114 TI - Alkalization of urine during sulfonamide therapy. PMID- 21019115 TI - ACTIVITY of a new antimalarial agent, chloroquine (SN 7618). PMID- 21019116 TI - Delayed sensitization to penicillin similar to serum sickness. PMID- 21019118 TI - Digitalis intoxication. PMID- 21019117 TI - Hospital service in the United States. PMID- 21019119 TI - Diaphragmatic hernia; with report of a case. PMID- 21019120 TI - Torula infection of the nervous system. PMID- 21019121 TI - Leukoplakic vulvitis and its relationship to the development of carcinoma of the vulva; report of cases. PMID- 21019122 TI - Mixed tumor of the tongue; review of the literature; report of a case. PMID- 21019123 TI - The use of demerol in obstetrics. PMID- 21019124 TI - Studies on the complement fixation antigens of influenza viruses types A and B. PMID- 21019125 TI - Precipitin reactions of highly purified influenza viruses and related materials. PMID- 21019126 TI - Colorado tick fever and dengue; an experimental immunological and clinical comparison. PMID- 21019127 TI - Antibody formation in volunteers following injection of pneumococci or their type specific polysaccharides. PMID- 21019128 TI - Mouse-protective titers of sera of volunteers following injection of pneumococci or their type-specific polysaccharides. PMID- 21019129 TI - A neuropathological study of acute human poliomyelitis with special reference to the ititial lesion and to various potential portals of entry. PMID- 21019130 TI - Cancer of the uterus. PMID- 21019131 TI - Thyrotropic exophthalmos. PMID- 21019132 TI - Carcinoma of the cervix. PMID- 21019133 TI - Metastastic carcinoma after forty years. PMID- 21019134 TI - Cancer of the middle ear; report of four cases. PMID- 21019135 TI - Traumatic neurosis of war. PMID- 21019136 TI - Resume of medical activities at German Prisoner of War Camp, Fort Lewis, Washington, August, 1944-August 1945. PMID- 21019137 TI - Cancer control progress. PMID- 21019138 TI - The county medical society in the present crisis. PMID- 21019139 TI - Our own insurance company (Mutual Medical Care, Inc.). PMID- 21019140 TI - Pernicious and resistant forms of malaria. PMID- 21019141 TI - Menstrual disorders. PMID- 21019142 TI - Intra group reaction in an Rh-expectant mother and associated considerations. PMID- 21019143 TI - Facial palsy? PMID- 21019144 TI - Our impressions of sulphathiazole. PMID- 21019145 TI - Prolapse uterus following normal labour. PMID- 21019147 TI - Present trends in psychiatry. PMID- 21019146 TI - Re-formed gallbladder; a review of 42 cases. PMID- 21019148 TI - Toxic manifestations of large doses of vitamin D as used in the treatment of arthritis. PMID- 21019150 TI - The significance of vaginal bleeding. PMID- 21019149 TI - Analgesia and analgesic agents. PMID- 21019151 TI - Epidemic ringworm of the scalp in children. PMID- 21019152 TI - [Carcinoma of the pyloric end of the stomach]. PMID- 21019153 TI - Visual technics in medical education. PMID- 21019154 TI - Visual education in anatomy. PMID- 21019155 TI - The use of visual aids in the teaching of medical bacteriology. PMID- 21019157 TI - Some things we have learned about medical motion pictures. PMID- 21019156 TI - The integration of visual education into the medical school curriculum. PMID- 21019158 TI - Medical science at war. PMID- 21019159 TI - [Not Available]. PMID- 21019160 TI - [Not Available]. PMID- 21019161 TI - [Not Available]. PMID- 21019162 TI - [Not Available]. PMID- 21019163 TI - [Not Available]. PMID- 21019164 TI - [Not Available]. PMID- 21019165 TI - [Not Available]. PMID- 21019166 TI - [Not Available]. PMID- 21019167 TI - [Not Available]. PMID- 21019168 TI - [Not Available]. PMID- 21019169 TI - [Not Available]. PMID- 21019170 TI - [Not Available]. PMID- 21019172 TI - [Not Available]. PMID- 21019171 TI - [Not Available]. PMID- 21019173 TI - [Not Available]. PMID- 21019174 TI - [Not Available]. PMID- 21019175 TI - [Not Available]. PMID- 21019176 TI - [Not Available]. PMID- 21019177 TI - [Not Available]. PMID- 21019178 TI - [Not Available]. PMID- 21019179 TI - [Not Available]. PMID- 21019180 TI - [Not Available]. PMID- 21019181 TI - [Not Available]. PMID- 21019182 TI - [Not Available]. PMID- 21019183 TI - [Not Available]. PMID- 21019184 TI - [Not Available]. PMID- 21019185 TI - Role of fats and certain other dietary components in vitamin E deficiency. PMID- 21019187 TI - Non-specific localized granulomatous ulcer of the jejunum. PMID- 21019186 TI - Observations on two cases of human filariasis (Wuchereria bancrofti and Mansonella ozzardi). PMID- 21019189 TI - The miliary form of pulmonary sarcoidosis. PMID- 21019188 TI - Chronic empyema associated with osteomyelitis of spine and ribs. PMID- 21019190 TI - Staphylococcus aureus empyema in an infant, aged six weeks; Streptococcus viridans empyema in an infant, aged twenty-one months. PMID- 21019191 TI - Periarteritis nodosa. PMID- 21019192 TI - A control program in a mettopolitan area for tuberculosis among Negroes. PMID- 21019193 TI - Some questions text-books do not answer. PMID- 21019194 TI - Gastric syphilis. PMID- 21019195 TI - Local examination of the thyroid gland. PMID- 21019196 TI - Sickle cell anemia as a clinical entity. PMID- 21019197 TI - The laboratory as a necessity for a conclusive diagnosis. PMID- 21019198 TI - STREPTOMYCIN moves closer to clinical use. PMID- 21019199 TI - Remarks on the treatment of essential hypertension. PMID- 21019200 TI - Weil's disease. PMID- 21019201 TI - [Not Available]. PMID- 21019202 TI - [Not Available]. PMID- 21019203 TI - [Not Available]. PMID- 21019204 TI - [Not Available]. PMID- 21019205 TI - [Not Available]. PMID- 21019206 TI - [Not Available]. PMID- 21019207 TI - [Not Available]. PMID- 21019209 TI - [Not Available]. PMID- 21019208 TI - [Not Available]. PMID- 21019210 TI - The significance of the Rh factor. PMID- 21019211 TI - Fulminating meningococcemia, report of twelve cases. PMID- 21019212 TI - Endocrine disorders as related to pelvic pain. PMID- 21019213 TI - Evaluation of methods for early diagnosis of pulmonary tuberculosis. PMID- 21019214 TI - The search for a philosophy of medicine. PMID- 21019215 TI - Penicillin therapy; clinical and laboratory observations on four hundred cases. PMID- 21019216 TI - Paralytic ileus in severe hypothyroidism. PMID- 21019217 TI - Gravid uterus in a strangulated hernia. PMID- 21019218 TI - An unusual recto-vesical injury. PMID- 21019219 TI - RESTORATION of function in peripheral nerve injuries. PMID- 21019220 TI - An automatic pneumoencephalographic apparatus. PMID- 21019221 TI - NATIONAL Health Service Bill. PMID- 21019222 TI - CHINESE military hospital. PMID- 21019223 TI - Simple technique of tendon suture. PMID- 21019224 TI - Thrombosis; early diagnosis and abortive treatment with heparin. PMID- 21019225 TI - Effect of pH of the medium on activity of streptomycin and penicillin and other chemotherapeutic substances. PMID- 21019226 TI - Gas-gangrene following injection of adrenaline. PMID- 21019227 TI - Bact. coli meningitis, treated with sulphathiazole. PMID- 21019228 TI - PNEUMOCONIOSIS in South Wales coalmines. PMID- 21019229 TI - Apparatus for administration of pentothal and curare solutions. PMID- 21019230 TI - Health centres of today; Bristol. PMID- 21019232 TI - [Not Available]. PMID- 21019231 TI - Autopsies for the coroner. PMID- 21019233 TI - [Not Available]. PMID- 21019234 TI - [Not Available]. PMID- 21019235 TI - [Not Available]. PMID- 21019236 TI - [Not Available]. PMID- 21019238 TI - [Not Available]. PMID- 21019237 TI - [Not Available]. PMID- 21019239 TI - [Not Available]. PMID- 21019240 TI - [Not Available]. PMID- 21019241 TI - The diagnosis, prevention and treatment of pertussis. PMID- 21019242 TI - Medical critique; on the stethoscope. PMID- 21019243 TI - Diagnosis of injured knee cartilages. PMID- 21019244 TI - Pathological lesions of the appendices epiploicae; with a report of one case of torsion. PMID- 21019245 TI - Magic and medicine. PMID- 21019246 TI - Volvulus of the sigmoid. PMID- 21019247 TI - [Not Available]. PMID- 21019248 TI - [Not Available]. PMID- 21019249 TI - [Not Available]. PMID- 21019250 TI - [Not Available]. PMID- 21019251 TI - [Not Available]. PMID- 21019252 TI - [Not Available]. PMID- 21019254 TI - [Not Available]. PMID- 21019253 TI - [Not Available]. PMID- 21019255 TI - [Not Available]. PMID- 21019256 TI - [Not Available]. PMID- 21019257 TI - [Not Available]. PMID- 21019258 TI - [Not Available]. PMID- 21019259 TI - [Not Available]. PMID- 21019260 TI - [Not Available]. PMID- 21019261 TI - Tuberculous pleural effusion. PMID- 21019262 TI - Acute disseminated miliary tuberculosis. PMID- 21019263 TI - Tuberculous meningitis with unusual features in young adults. PMID- 21019264 TI - Thiouracil therapy in the preoperative preparation of thyrotoxic patients. PMID- 21019266 TI - Carcinoma of the colon and rectum. PMID- 21019265 TI - Clinical value of gastroscopy. PMID- 21019267 TI - Diagnosis and management of ulcerative colitis. PMID- 21019269 TI - The problem of nutrition in the treatment of the prolonged hospitalized patient. PMID- 21019268 TI - Mechanical intestinal obstruction following war wounds of the abdomen. PMID- 21019270 TI - Malnutrition. PMID- 21019271 TI - Acute idiopathic porphyria; report of a case. PMID- 21019272 TI - Acute muscular atrophy with porphyria; report of a case. PMID- 21019273 TI - Thrombocytopenic purpura following rubella. PMID- 21019274 TI - Penicillin therapy in the management of the pyodermas and secondary pyodermic infections; report of seventy cases. PMID- 21019275 TI - [Not Available]. PMID- 21019276 TI - Postwar aspects of the trench foot problem. PMID- 21019277 TI - Rupture of the intervertebral disk. PMID- 21019278 TI - Postdiphtheritic paralysis. PMID- 21019279 TI - The significance of a psychiatric diagnosis. PMID- 21019280 TI - The treatment of the neuropsychiatric patient in an Army hospital. PMID- 21019281 TI - Psychological aspects of the paraplegic patient. PMID- 21019282 TI - [Not Available]. PMID- 21019283 TI - [Not Available]. PMID- 21019284 TI - [Not Available]. PMID- 21019285 TI - [Not Available]. PMID- 21019286 TI - [Not Available]. PMID- 21019287 TI - [Not Available]. PMID- 21019288 TI - [Not Available]. PMID- 21019289 TI - [Not Available]. PMID- 21019290 TI - [Not Available]. PMID- 21019291 TI - Solutions for a problem-office. PMID- 21019292 TI - AMERICAN medicine said to be using the wrong symbol. PMID- 21019293 TI - Health insurance new trend in industry-labor pacts. PMID- 21019294 TI - [Not Available]. PMID- 21019295 TI - [Not Available]. PMID- 21019296 TI - [Not Available]. PMID- 21019297 TI - [Not Available]. PMID- 21019298 TI - [Not Available]. PMID- 21019299 TI - [Not Available]. PMID- 21019300 TI - [Not Available]. PMID- 21019301 TI - [Not Available]. PMID- 21019303 TI - Penicillin sensitivity of streptococci, mostly of groups A, B, C and G. PMID- 21019302 TI - [Not Available]. PMID- 21019304 TI - Fractures of the carpal scaphoid. PMID- 21019305 TI - Placenta praevia. PMID- 21019306 TI - Report on a series of cases of sinusitis treated by chemotherapy at an Australian general hospital. PMID- 21019307 TI - An analysis of deformities among recruits, with remarks on sub-standard types. PMID- 21019308 TI - Suture of deep soft tissue war wounds aided by penicillin therapy. PMID- 21019309 TI - Leprosy; a report of nine cases among natives of the Mount Hagen area in New Guinea. PMID- 21019310 TI - Hypertensive arteriosclerosis with retinal changes. PMID- 21019311 TI - Wilms's tumour. PMID- 21019312 TI - Intraperitoneal rupture of the urinary bladder. PMID- 21019313 TI - Inguinal hernia and its repair. PMID- 21019314 TI - NIGHT cramps in young men. PMID- 21019315 TI - The diagnosis and modern treatment of lupus vulgaris. PMID- 21019316 TI - Chronic cancer. PMID- 21019317 TI - The treatment of chronic diseases of the chest by homoeopathy. PMID- 21019318 TI - Drinking at meals. PMID- 21019319 TI - [HEALTH Services Bill; index]. PMID- 21019320 TI - A National Health Service Bill; comments. PMID- 21019321 TI - Anorectal fistula. PMID- 21019322 TI - A safe, simple and efficient method of intestinal anastomosis. PMID- 21019323 TI - Desmoid tumor. PMID- 21019324 TI - Case of abdominal pregnancy. PMID- 21019326 TI - Influenza. PMID- 21019325 TI - Music re-education. PMID- 21019327 TI - Functional disorders of the genito-urinary tract. PMID- 21019328 TI - A differential diagnosis of earache. PMID- 21019329 TI - Factors in rural health in Minnesota. PMID- 21019330 TI - Tropical disease hazards in the northwest. PMID- 21019331 TI - Facial injuries. PMID- 21019332 TI - The Rh factor. PMID- 21019333 TI - The treatment of acute arterial occlusion of the extremities with special reference to anticoagulant therapy. PMID- 21019334 TI - Diagnostic case report. PMID- 21019335 TI - Cancer detection centers and allied cancer projects. PMID- 21019336 TI - The significance of bleeding from the rectum. PMID- 21019337 TI - Virus aspects of carcinoma. PMID- 21019338 TI - Bronchiogenic carcinoma. PMID- 21019339 TI - Several wartime therapeutic advancements. PMID- 21019340 TI - The modern treatment of Ludwig's angina. PMID- 21019341 TI - Postural or orthostatic hypotension. PMID- 21019342 TI - Differential diagnosis of nasal allergy. PMID- 21019343 TI - Roseola infantum. PMID- 21019345 TI - [Not Available]. PMID- 21019344 TI - [Not Available]. PMID- 21019346 TI - [Not Available]. PMID- 21019347 TI - [Not Available]. PMID- 21019348 TI - [Not Available]. PMID- 21019349 TI - Mental public health; a blueprint. PMID- 21019350 TI - Penicillin in medicine. PMID- 21019351 TI - Use of penicillin in urology. PMID- 21019352 TI - Pharmacology and methods of administration. PMID- 21019353 TI - Frontal lobotomy. PMID- 21019354 TI - Trauma of the lower urinary tract; a roentgenologic study. PMID- 21019355 TI - Recurrent meningococcal meningitis; report of a case. PMID- 21019356 TI - The dangers of modern insulin syringes. PMID- 21019357 TI - Arteriovenous aneurysm of the great vessels of the neck. PMID- 21019358 TI - Syphilis (concluded). PMID- 21019359 TI - Sub-acute glomerulonephritis. PMID- 21019360 TI - Adenocarcinoma of lung. PMID- 21019361 TI - The repair of cranial defects with special reference to the use of cancellous bone. PMID- 21019362 TI - Lack of a specific urethral lesion in exertional urinary incontinence. PMID- 21019363 TI - Pyogenic liver abscess; review of the literature and report of a case successfully treated by operation and penicillin. PMID- 21019364 TI - Abdominal surgery. PMID- 21019365 TI - Symmetrical necrosis of renal cortex. PMID- 21019366 TI - Idiopathic acute myocarditis (?infuenzal myocarditis). PMID- 21019367 TI - Psychosomatic backache. PMID- 21019368 TI - The use of phthalylsulfathiazole (sulfathalidine) in colonic surgery. PMID- 21019369 TI - Chronic disability in mild cases of trench foot. PMID- 21019370 TI - Hemorrhage from the gall bladder. PMID- 21019371 TI - Sensitivity to tincture of merthiolate. PMID- 21019372 TI - Diabetes mellitus. PMID- 21019373 TI - Ruptured syphilitic aneurysm of aorta; clinicopathological exercises. PMID- 21019374 TI - Operative injury to common duct; immediate repair; case report. PMID- 21019375 TI - Penetrating abdominal wounds; report of 21 operated cases. PMID- 21019376 TI - Penicillin in tetanus; report of toxic reactions following its use in two other cases. PMID- 21019377 TI - Carcinoma of Bartholin's gland. PMID- 21019378 TI - Some interesting observations in routine pregnancy studies. PMID- 21019379 TI - Weil's disease. PMID- 21019380 TI - The physician's responsibility in cancer control. PMID- 21019381 TI - Community aspects of venereal-disease control in Harlem. PMID- 21019382 TI - Proctologic problems in a military hospital. PMID- 21019383 TI - Rehabilitation of the tuberculous. PMID- 21019384 TI - Observations of penicillin therapy in gonorrhea. PMID- 21019385 TI - Palindromic rheumatism in children. PMID- 21019386 TI - Treatment of subacute bacterial endocarditis with penicillin; report of ten cases. PMID- 21019388 TI - Coexistence of gout and metabolic craniopathy. PMID- 21019387 TI - Elicitation of the big-toe response (Babinski sign) in ticklish subjects. PMID- 21019389 TI - Multiple hemorrhagic telangiectasis (Rendu-Osler-Weber disease); report of 4 cases. PMID- 21019390 TI - Recovery of a patient with agranulocytosis by the administration of blood from a febrile donor. PMID- 21019391 TI - Haemolytic disease of the newborn; a clinical review of the Rh and other blood factors. PMID- 21019392 TI - Anatomy of the bronchial tree. PMID- 21019393 TI - Testosterone therapy in eunuchoidism. PMID- 21019394 TI - Niemann-Pick disease; report of a case showing calcification in the adrenal glands. PMID- 21019395 TI - The advantages of early skin grafting. PMID- 21019396 TI - Abdominal pregnancy; report of a case. PMID- 21019397 TI - The results of thoracoplasty and crushing of the phrenic nerve; an analysis of cases from the Waipawa Hospital Board Chest Committee. PMID- 21019398 TI - Legal responsibility of medical staff of public hospitals. PMID- 21019399 TI - Management of obscure gastrointestinal hemorrhage. PMID- 21019400 TI - Respiratory allergy: a plea for a basic nomenclature. PMID- 21019401 TI - Cor biloculare: report of a case. PMID- 21019402 TI - The physician and the cancer patient. PMID- 21019403 TI - Sodium pentothal combined anesthesia. PMID- 21019405 TI - Primary carcinoma of the gallbladder: a review of cases at St. Alexis Hospital. PMID- 21019404 TI - The diagnosis of vegetal foreign bodies in the lower respiratory tract. PMID- 21019406 TI - Comments and suggestions on the psychiatric aspects of the vocational rehabilitation program. PMID- 21019407 TI - An unusual case of diffuse carcinoma of the stomach. PMID- 21019408 TI - [Not Available]. PMID- 21019409 TI - [Not Available]. PMID- 21019410 TI - [Not Available]. PMID- 21019411 TI - [Not Available]. PMID- 21019412 TI - [Not Available]. PMID- 21019413 TI - [Not Available]. PMID- 21019414 TI - [Not Available]. PMID- 21019415 TI - [Not Available]. PMID- 21019416 TI - [Not Available]. PMID- 21019417 TI - [Not Available]. PMID- 21019418 TI - [Not Available]. PMID- 21019419 TI - Complications of bronchial asthma and their association with bronchostenosis. PMID- 21019420 TI - The radiation treatment of carcinoma of the female urethra. PMID- 21019421 TI - Clinical significance of certain respiratory symptoms. PMID- 21019422 TI - The medical management of incomplete abortion. PMID- 21019423 TI - Suture technique for small wounds. PMID- 21019424 TI - Contusions and sprains. PMID- 21019425 TI - Superficial wounds. PMID- 21019426 TI - Minor dislocations. PMID- 21019427 TI - Minor injuries of the hand. PMID- 21019428 TI - Injuries to tendons. PMID- 21019429 TI - Ganglia and superficial tumours. PMID- 21019430 TI - Boils, carbuncles and cellulitis. PMID- 21019431 TI - Burns of slight degree. PMID- 21019432 TI - Haemorrhoids and their treatment. PMID- 21019433 TI - Some everyday problems in the treatment of varicose veins. PMID- 21019434 TI - The early recognition of disease; digestive disorders. PMID- 21019435 TI - Preventive inoculation against infectious disease in childhood. PMID- 21019436 TI - Treatment of diarrhoea and vomiting in infancy. PMID- 21019437 TI - [Not Available]. PMID- 21019438 TI - [Not Available]. PMID- 21019439 TI - [Not Available]. PMID- 21019440 TI - [Not Available]. PMID- 21019441 TI - [Not Available]. PMID- 21019442 TI - [Not Available]. PMID- 21019443 TI - [Not Available]. PMID- 21019444 TI - [Not Available]. PMID- 21019445 TI - [Not Available]. PMID- 21019446 TI - [Not Available]. PMID- 21019447 TI - [Not Available]. PMID- 21019448 TI - [Not Available]. PMID- 21019450 TI - [Not Available]. PMID- 21019449 TI - [Not Available]. PMID- 21019451 TI - [Not Available]. PMID- 21019452 TI - [Not Available]. PMID- 21019453 TI - [Not Available]. PMID- 21019454 TI - [Not Available]. PMID- 21019455 TI - [Not Available]. PMID- 21019456 TI - [Not Available]. PMID- 21019457 TI - [Not Available]. PMID- 21019458 TI - [Not Available]. PMID- 21019460 TI - [Not Available]. PMID- 21019459 TI - [Not Available]. PMID- 21019461 TI - [Not Available]. PMID- 21019462 TI - [Not Available]. PMID- 21019463 TI - [Not Available]. PMID- 21019464 TI - [Not Available]. PMID- 21019465 TI - [Not Available]. PMID- 21019466 TI - [Not Available]. PMID- 21019467 TI - [Not Available]. PMID- 21019469 TI - [Not Available]. PMID- 21019468 TI - [Not Available]. PMID- 21019470 TI - [Not Available]. PMID- 21019472 TI - [Not Available]. PMID- 21019471 TI - [Not Available]. PMID- 21019473 TI - [Not Available]. PMID- 21019474 TI - [Not Available]. PMID- 21019475 TI - [Not Available]. PMID- 21019476 TI - [Not Available]. PMID- 21019477 TI - [Not Available]. PMID- 21019478 TI - [Not Available]. PMID- 21019479 TI - [Not Available]. PMID- 21019480 TI - [Not Available]. PMID- 21019481 TI - [Not Available]. PMID- 21019482 TI - [Not Available]. PMID- 21019483 TI - [Not Available]. PMID- 21019484 TI - [Not Available]. PMID- 21019485 TI - [Not Available]. PMID- 21019486 TI - [Not Available]. PMID- 21019487 TI - [Not Available]. PMID- 21019488 TI - [Not Available]. PMID- 21019489 TI - [Not Available]. PMID- 21019490 TI - [Not Available]. PMID- 21019491 TI - [Not Available]. PMID- 21019492 TI - [Not Available]. PMID- 21019493 TI - [Not Available]. PMID- 21019494 TI - [Not Available]. PMID- 21019495 TI - [Not Available]. PMID- 21019496 TI - [Not Available]. PMID- 21019497 TI - [Not Available]. PMID- 21019498 TI - [Not Available]. PMID- 21019499 TI - [Not Available]. PMID- 21019500 TI - [Not Available]. PMID- 21019501 TI - [Not Available]. PMID- 21019502 TI - [Not Available]. PMID- 21019503 TI - [Not Available]. PMID- 21019504 TI - [Not Available]. PMID- 21019506 TI - [Not Available]. PMID- 21019505 TI - [Not Available]. PMID- 21019507 TI - [Not Available]. PMID- 21019508 TI - [Not Available]. PMID- 21019509 TI - [Not Available]. PMID- 21019510 TI - Pernicious anemia in a Chinese patient. PMID- 21019511 TI - Transurethral prostatic resection in the presence of azotemia. PMID- 21019512 TI - Increase in resistance of tubercle bacilli to streptomycin; a preliminary report. PMID- 21019513 TI - Treatment of tuberculosis of the larynx with streptomycin; report of case. PMID- 21019514 TI - Statistics and medicine; the need for close co-operation between the physician and statistician in medical statistics. PMID- 21019515 TI - [Not Available]. PMID- 21019516 TI - [Not Available]. PMID- 21019517 TI - [Not Available]. PMID- 21019518 TI - [Not Available]. PMID- 21019519 TI - [Not Available]. PMID- 21019521 TI - [Not Available]. PMID- 21019520 TI - [Not Available]. PMID- 21019522 TI - [Not Available]. PMID- 21019523 TI - [Not Available]. PMID- 21019524 TI - [Not Available]. PMID- 21019525 TI - [Not Available]. PMID- 21019526 TI - [Not Available]. PMID- 21019527 TI - [Not Available]. PMID- 21019528 TI - [Not Available]. PMID- 21019529 TI - [Not Available]. PMID- 21019530 TI - [Not Available]. PMID- 21019531 TI - [Not Available]. PMID- 21019532 TI - [Not Available]. PMID- 21019533 TI - [Not Available]. PMID- 21019534 TI - [Not Available]. PMID- 21019535 TI - [Not Available]. PMID- 21019536 TI - [Not Available]. PMID- 21019537 TI - [Not Available]. PMID- 21019538 TI - A study of the behavior of gases in the pleural cavity in artificial pneumothorax therapy for pulmonary tuberculosis. PMID- 21019539 TI - The behavior of gases in bilateral pneumothoraces. PMID- 21019540 TI - Experiences with arthrodesis for tuberculosis of the hip. PMID- 21019541 TI - Bronchography, details of a simple method. PMID- 21019542 TI - Oral penicillin in the treatment of oral lesions. PMID- 21019543 TI - Primary tuberculosis of the skin; case reports. PMID- 21019544 TI - The treatment of amoebiasis; with special reference to chronic amoebic dysentery. PMID- 21019545 TI - [Not Available]. PMID- 21019546 TI - Temporal arteritis; a generalized vascular disease. PMID- 21019547 TI - The lead content of the blood and its relation to rarefying processes in bone. PMID- 21019548 TI - Chronic ulcerative colitis. PMID- 21019549 TI - A review of recent developments on reticulo-endothelial immune serum (REIS). PMID- 21019550 TI - APHASIA. PMID- 21019551 TI - The tonsil and adenoid problem. PMID- 21019552 TI - [Not Available]. PMID- 21019553 TI - [Not Available]. PMID- 21019554 TI - [Not Available]. PMID- 21019555 TI - [Not Available]. PMID- 21019556 TI - [Not Available]. PMID- 21019557 TI - [Not Available]. PMID- 21019558 TI - [Not Available]. PMID- 21019559 TI - [Not Available]. PMID- 21019560 TI - [Not Available]. PMID- 21019561 TI - [Not Available]. PMID- 21019562 TI - [Not Available]. PMID- 21019563 TI - [Not Available]. PMID- 21019564 TI - [Not Available]. PMID- 21019565 TI - [Not Available]. PMID- 21019566 TI - [Not Available]. PMID- 21019567 TI - [Not Available]. PMID- 21019568 TI - [Not Available]. PMID- 21019569 TI - [Not Available]. PMID- 21019570 TI - [Not Available]. PMID- 21019571 TI - [Not Available]. PMID- 21019572 TI - [Not Available]. PMID- 21019573 TI - [Not Available]. PMID- 21019574 TI - [Not Available]. PMID- 21019576 TI - [Not Available]. PMID- 21019575 TI - [Not Available]. PMID- 21019577 TI - [Not Available]. PMID- 21019578 TI - [Not Available]. PMID- 21019579 TI - [Not Available]. PMID- 21019580 TI - [Not Available]. PMID- 21019581 TI - [Not Available]. PMID- 21019583 TI - [Not Available]. PMID- 21019582 TI - [Not Available]. PMID- 21019584 TI - [Not Available]. PMID- 21019585 TI - [Not Available]. PMID- 21019586 TI - [Not Available]. PMID- 21019587 TI - [Not Available]. PMID- 21019588 TI - [Not Available]. PMID- 21019589 TI - [Not Available]. PMID- 21019590 TI - [Not Available]. PMID- 21019591 TI - [Not Available]. PMID- 21019592 TI - [Not Available]. PMID- 21019594 TI - [Not Available]. PMID- 21019593 TI - [Not Available]. PMID- 21019595 TI - [Not Available]. PMID- 21019596 TI - [Not Available]. PMID- 21019597 TI - [Not Available]. PMID- 21019598 TI - [Not Available]. PMID- 21019599 TI - [Not Available]. PMID- 21019600 TI - [Not Available]. PMID- 21019601 TI - [Not Available]. PMID- 21019602 TI - [Not Available]. PMID- 21019603 TI - [Not Available]. PMID- 21019604 TI - [Not Available]. PMID- 21019605 TI - [Not Available]. PMID- 21019606 TI - [Not Available]. PMID- 21019608 TI - [Not Available]. PMID- 21019607 TI - [Not Available]. PMID- 21019609 TI - [Not Available]. PMID- 21019610 TI - [Not Available]. PMID- 21019611 TI - [Not Available]. PMID- 21019612 TI - [Not Available]. PMID- 21019613 TI - [Not Available]. PMID- 21019614 TI - [Not Available]. PMID- 21019615 TI - [Not Available]. PMID- 21019616 TI - [Not Available]. PMID- 21019617 TI - [Not Available]. PMID- 21019618 TI - [Not Available]. PMID- 21019619 TI - [Not Available]. PMID- 21019620 TI - [Not Available]. PMID- 21019621 TI - [Not Available]. PMID- 21019622 TI - [Not Available]. PMID- 21019623 TI - A case of nephrolithiasis following trauma. PMID- 21019625 TI - [Not Available]. PMID- 21019626 TI - [Not Available]. PMID- 21019624 TI - Some medical aspects of Czecho-Slovakia. PMID- 21019627 TI - [Not Available]. PMID- 21019628 TI - [Not Available]. PMID- 21019629 TI - [Not Available]. PMID- 21019630 TI - [Not Available]. PMID- 21019631 TI - [Not Available]. PMID- 21019632 TI - [Not Available]. PMID- 21019633 TI - [Not Available]. PMID- 21019634 TI - [Not Available]. PMID- 21019635 TI - [Not Available]. PMID- 21019636 TI - [Not Available]. PMID- 21019637 TI - [Not Available]. PMID- 21019638 TI - [Not Available]. PMID- 21019639 TI - [Not Available]. PMID- 21019640 TI - [Not Available]. PMID- 21019641 TI - [Not Available]. PMID- 21019642 TI - [Not Available]. PMID- 21019643 TI - [Not Available]. PMID- 21019644 TI - [Not Available]. PMID- 21019645 TI - [Not Available]. PMID- 21019646 TI - [Not Available]. PMID- 21019647 TI - [Not Available]. PMID- 21019648 TI - [Not Available]. PMID- 21019649 TI - [Not Available]. PMID- 21019650 TI - [Not Available]. PMID- 21019651 TI - [Not Available]. PMID- 21019652 TI - [Not Available]. PMID- 21019653 TI - [Not Available]. PMID- 21019654 TI - [Not Available]. PMID- 21019655 TI - [Not Available]. PMID- 21019656 TI - [Not Available]. PMID- 21019657 TI - [Not Available]. PMID- 21019658 TI - [Not Available]. PMID- 21019660 TI - [Not Available]. PMID- 21019659 TI - [Not Available]. PMID- 21019661 TI - [Not Available]. PMID- 21019662 TI - [Not Available]. PMID- 21019663 TI - [Not Available]. PMID- 21019664 TI - [Not Available]. PMID- 21019665 TI - [Not Available]. PMID- 21019666 TI - [Not Available]. PMID- 21019667 TI - [Not Available]. PMID- 21019668 TI - [Not Available]. PMID- 21019669 TI - [Not Available]. PMID- 21019671 TI - [Not Available]. PMID- 21019670 TI - [Not Available]. PMID- 21019672 TI - [Not Available]. PMID- 21019673 TI - [Not Available]. PMID- 21019674 TI - [Not Available]. PMID- 21019675 TI - [Not Available]. PMID- 21019676 TI - [Not Available]. PMID- 21019677 TI - [Not Available]. PMID- 21019678 TI - [Not Available]. PMID- 21019679 TI - [Not Available]. PMID- 21019680 TI - [Not Available]. PMID- 21019681 TI - [Not Available]. PMID- 21019682 TI - [Not Available]. PMID- 21019683 TI - [Not Available]. PMID- 21019684 TI - [Not Available]. PMID- 21019686 TI - [Not Available]. PMID- 21019685 TI - [Not Available]. PMID- 21019687 TI - [Not Available]. PMID- 21019688 TI - [Not Available]. PMID- 21019689 TI - [Not Available]. PMID- 21019690 TI - Regressive changes in leprosy under promin therapy. PMID- 21019691 TI - Usual and unusual findings in tuberculosis of infancy. PMID- 21019692 TI - Treatment of some common infections of the bowel with sulfonamide drugs. PMID- 21019693 TI - Treatment of peripheral nerve injuries. PMID- 21019694 TI - The management of placenta previa. PMID- 21019695 TI - Roentgen diagnosis of placenta previa without contrast material. PMID- 21019697 TI - Towel clip fixation of fresh clavicular fractures. PMID- 21019696 TI - Spinal fusion following removal of intervertebral disk. PMID- 21019698 TI - Operative treatment of aneurysm and arteriovenous fistula. PMID- 21019699 TI - [Not Available]. PMID- 21019700 TI - [Not Available]. PMID- 21019701 TI - [Not Available]. PMID- 21019702 TI - [Not Available]. PMID- 21019703 TI - [Not Available]. PMID- 21019704 TI - [Not Available]. PMID- 21019705 TI - [Not Available]. PMID- 21019706 TI - [Not Available]. PMID- 21019707 TI - [Not Available]. PMID- 21019708 TI - [Not Available]. PMID- 21019709 TI - A new technique for recording the esophagocardiogram. PMID- 21019710 TI - Coarctation of the aorta. PMID- 21019711 TI - Diphtheritic paralysis. PMID- 21019713 TI - Physical fitness clinics. PMID- 21019712 TI - Apparent spontaneous hypoglycemic crises in a patient with long-standing diabetes mellitus; report of a case. PMID- 21019714 TI - [Not Available]. PMID- 21019715 TI - [Not Available]. PMID- 21019716 TI - [Not Available]. PMID- 21019717 TI - [Not Available]. PMID- 21019718 TI - [Not Available]. PMID- 21019719 TI - [Not Available]. PMID- 21019720 TI - [Not Available]. PMID- 21019721 TI - [Not Available]. PMID- 21019722 TI - [Not Available]. PMID- 21019723 TI - [Not Available]. PMID- 21019724 TI - [Not Available]. PMID- 21019725 TI - [Not Available]. PMID- 21019726 TI - [Not Available]. PMID- 21019727 TI - [Not Available]. PMID- 21019728 TI - [Not Available]. PMID- 21019729 TI - [Not Available]. PMID- 21019730 TI - [Not Available]. PMID- 21019731 TI - [Not Available]. PMID- 21019732 TI - [Not Available]. PMID- 21019733 TI - [Not Available]. PMID- 21019734 TI - [Not Available]. PMID- 21019735 TI - [Not Available]. PMID- 21019736 TI - Elephant man. PMID- 21019738 TI - The test of irradiation in intrathoracic lesions. PMID- 21019737 TI - Benadryl (beta-dimethylaminoethyl benzhydryl ether hydrochloride) in the treatment of hay fever and asthma. PMID- 21019739 TI - The effect of dextrose upon the rate of sodium loss in the postoperative patient. PMID- 21019740 TI - The effects of blockade of the autonomic ganglia in man; preliminary observations on the use of tetraethyl ammonium bromide. PMID- 21019741 TI - Scott's Northern party; a study of contrast and survival in the Antarctic. PMID- 21019742 TI - The social value of biochemistry. PMID- 21019743 TI - Hamilton Russell traction; a treatment for pertrochanteric fractures of the femur. PMID- 21019744 TI - Motherhood and momism; effect on the nation. PMID- 21019745 TI - Endometriosis; a review and presentation of a case. PMID- 21019746 TI - Baldness. PMID- 21019747 TI - Tropical climates and their effects on man. PMID- 21019748 TI - Hiatus hernia. PMID- 21019749 TI - Venereal disease as soldiers return. PMID- 21019750 TI - Biologic false positive serologic tests for syphilis; a study of 100 cases. PMID- 21019751 TI - A minor epidemic of Salmonella infection. PMID- 21019752 TI - The early clinical recognition of coronary artery disease; with ten case reports. PMID- 21019753 TI - Recent advances in the diagnosis and treatment of diseases of the external eye. PMID- 21019755 TI - Treatment of civilian casualties in Manila. PMID- 21019754 TI - Poliomyelitis; results of treatment. PMID- 21019756 TI - TREATMENT of puerperal mastitis. PMID- 21019757 TI - Laboratory aids in the diagnosis of cancer, especially prostatic cancer. PMID- 21019758 TI - Observations on the rehabilitation of movement in cerebral palsy problems. PMID- 21019759 TI - The runabout child. PMID- 21019760 TI - The threat of political medicine. PMID- 21019761 TI - A concise pharmacology of the antibiotic agents. PMID- 21019762 TI - Treatment of schizophrenia with intensive electric convulsive therapy; report of case. PMID- 21019763 TI - Newer contributions to the surgery of inguinal hernia. PMID- 21019764 TI - Penicillin therapy. PMID- 21019765 TI - Benzyl penicillin. PMID- 21019766 TI - Six hundred women doctors in Britain's Army. PMID- 21019767 TI - Medical observations in the Belgian Congo. PMID- 21019768 TI - The microscope or the guineapig? PMID- 21019769 TI - A gastro-enteritis cutbreak probably due to a bovine strain of vibrio. PMID- 21019770 TI - Mycotic endocarditis and meningitis; report of a case due to Monilia albicans. PMID- 21019771 TI - Electrical potentials from eye movements. PMID- 21019773 TI - Poliomyelitis in Alabama; epidemiological considerations. PMID- 21019772 TI - The effect of liver extract and methyl acetamide with para-chloro-xylenol on artificially induced leukopenia in rats. PMID- 21019775 TI - Psychiatry of the naval offender. PMID- 21019774 TI - A portable millivoltmeter. PMID- 21019776 TI - Treatment of small skin lesions. PMID- 21019777 TI - Operation of a pest control unit. PMID- 21019778 TI - MANUAL of the Medical Department. PMID- 21019779 TI - Some aspects of penicillin therapy in early syphilis. PMID- 21019780 TI - Analysis of medical repatriations; Canadian Army overseas. PMID- 21019781 TI - Psychosomatic medicine. PMID- 21019783 TI - Protruded intervertebral disc; a report on 60 operative cases. PMID- 21019782 TI - Foot notes. PMID- 21019784 TI - A rapid method for the routine determination of the sensitivity of bacteria to penicillin. PMID- 21019785 TI - An unusual case of sensitivity to T.A.B.T. simulating acute peritonitis. PMID- 21019786 TI - Thromboangitis obliterans (Buerger's disease). PMID- 21019787 TI - Severe allergic reactions to penicillin. PMID- 21019788 TI - Adjustment problems of successful Negro soldiers. PMID- 21019789 TI - Lumbar sympathetic block in the treatment of ureteral calculus. PMID- 21019790 TI - The common root cyst. PMID- 21019791 TI - A report of neuropsychiatry on Iwo Jima from 1 May to 1 October 1945. PMID- 21019793 TI - A clinical, laboratory, and experimental study of atypical lichen planus. PMID- 21019792 TI - Wounds of the abdomen. PMID- 21019794 TI - A study of malnutrition in Japanese prisoners of war. PMID- 21019795 TI - Topical penicillin in the treatment of burns. PMID- 21019796 TI - A report of 54 cases of tetanus complicating war wounds. PMID- 21019797 TI - Keratoconjunctivitis in the Philippine Islands. PMID- 21019798 TI - Traumatic intracerebral hematoma (a case report). PMID- 21019799 TI - Penicillin in septic surgery; a summary of ninety-one cases. PMID- 21019800 TI - Atropine treatment of hypoglycemic fatigue states in soldiers. PMID- 21019801 TI - Insect control in standing barracks; a report on the use of D.D.T. in Jamaica, February to October, 1945. PMID- 21019802 TI - The mass detection of anaemia by the copper sulphate blood gravity technique. PMID- 21019803 TI - Observations on an outbreak of trichinosis among German prisoners of war. PMID- 21019805 TI - A simple shelter. PMID- 21019804 TI - Under-water blast injury of the abdomen. PMID- 21019806 TI - A method of first-aid splinting for a fractured humerus with Cramers wire. PMID- 21019807 TI - The health of the civilian population of Tristan da Cunha. PMID- 21019808 TI - Lessons of war psychiatry. PMID- 21019809 TI - Administrative experiences at the Royal Naval Hospital, Haslar, in connection with the reception of casualties (March, 1942 to October, 1944). PMID- 21019810 TI - Aspects of the treatment of subtertian malaria. PMID- 21019811 TI - Naval repeat offenders; one aspect of psychiatric review. PMID- 21019812 TI - Notes on Kilindini. PMID- 21019814 TI - The control of secondary haemorrhage at the site of common femoral ligation in the groin. PMID- 21019813 TI - Meckel's diverticulum; incarceration in an inguinal hernia. PMID- 21019815 TI - Traumatic rupture of the left rectus abdominis. PMID- 21019816 TI - Anuria following sulphadiazine therapy treated by decapsulation of kidney and pyelostomy. PMID- 21019817 TI - Two cases of intraoccular tumour. PMID- 21019818 TI - Intraorbital abscess. PMID- 21019819 TI - The etiology and treatment of blepharitis; a study in military personnel. PMID- 21019820 TI - Aviation psychiatry. PMID- 21019821 TI - Early diagnosis and treatment of organic tension states (the psychoneuroses). PMID- 21019822 TI - Primary atypical pneumonia, virus type; a brief review; necropsy case presentation. PMID- 21019824 TI - Pilonidal cysts, their hospitalization. PMID- 21019823 TI - Infectious mononucleosis and acute infectious lumphocytosis. PMID- 21019825 TI - Hookworm disease in Latin America; a historical outline. PMID- 21019826 TI - Management of venereal disease in a field army under combat condition. PMID- 21019827 TI - Precipitating factors in the war neuroses. PMID- 21019828 TI - Military aspects of narcoepsy. PMID- 21019829 TI - The military neuropsychiatrist. PMID- 21019830 TI - [Not Available]. PMID- 21019831 TI - [Not Available]. PMID- 21019832 TI - [Not Available]. PMID- 21019833 TI - [Not Available]. PMID- 21019834 TI - [Not Available]. PMID- 21019836 TI - [Not Available]. PMID- 21019835 TI - [Not Available]. PMID- 21019837 TI - [Not Available]. PMID- 21019838 TI - [Not Available]. PMID- 21019839 TI - The electronic theory of valency. PMID- 21019840 TI - Chemistry and pharmacy. PMID- 21019841 TI - The automic nervous system and the hypothalamus. PMID- 21019842 TI - The insidious type of lead poisoning. PMID- 21019843 TI - Decolorisation of nicotinic acid extracts. PMID- 21019844 TI - Tamarind seed pectin. PMID- 21019845 TI - Chemotherapy of some acridine derivatives in fowl malaria. PMID- 21019846 TI - Complex compounds of mercuric chloride. PMID- 21019847 TI - Hair ball in the stomach of a calf. PMID- 21019848 TI - The carbohydrate-lipoid envelope of the leprosy germ. PMID- 21019849 TI - The chromosomes of Saccharomyces cerevisiae. PMID- 21019850 TI - A new species of genus Trichuris from cattle and buffaloes. PMID- 21019851 TI - Tropical medicine in the British Empire. PMID- 21019852 TI - Citrinin. PMID- 21019853 TI - Biologically active metabolic products of the mould Metarhizium glutinosum S. Pope. PMID- 21019854 TI - Occurrence of inorganic pyrophosphate in baker's yeast. PMID- 21019855 TI - Inactivation of insulin by intermediary fat metabolism products. PMID- 21019856 TI - Influence of starch in media used for the detection of heated bacterial spores. PMID- 21019858 TI - Interaction between regenerating limbs. PMID- 21019857 TI - Forced diuresis during hydropenia. PMID- 21019859 TI - Oxidation and reduction in chemistry. PMID- 21019860 TI - Resonance energies of acridine and phenazine. PMID- 21019861 TI - Disease and tropical industry. PMID- 21019862 TI - LEARNED societies and the diffusion of knowledge. PMID- 21019863 TI - Industrial dermatitis. PMID- 21019864 TI - COLLECTIONS of micro-organisms. PMID- 21019865 TI - Pituitary adrenotropic hormone, extract of suprarenal cortex, lymph, and lymphoid tissue. PMID- 21019866 TI - Absence of pseudo-cholinesteterase from the tissues of ruminants. PMID- 21019867 TI - Effect of ions upon the production of vitamins in the yeast cells. PMID- 21019868 TI - Constitution of the dianhydrides of sorbitol and iditol. PMID- 21019869 TI - Are there triflagellate gametes in the Foraminifera? PMID- 21019870 TI - Variation in the rate of growth of the milk-fish (Chanos chanos). PMID- 21019871 TI - Incidences of defective colour vision. PMID- 21019872 TI - The Donzellis. PMID- 21019873 TI - The relationship between common baldness and male sex hormones. PMID- 21019875 TI - The future of nutritional science. PMID- 21019874 TI - Nutrition as a world problem. PMID- 21019876 TI - The biological actions and therapeutic applications of the B-chloroethyl amines and sulfides. PMID- 21019877 TI - Some physical and biologic properties of subtilin and other antibiotics. PMID- 21019878 TI - A relation between size of the divalent cation and solubility of triple acetate salt of sodium. PMID- 21019879 TI - The mechanism of the therapeutic effect of iodine on the thyroid gland. PMID- 21019880 TI - Brain involvement as a possible cause of relapse after treatment in spirochetal relapsing fever. PMID- 21019881 TI - The ambiguity of international antitoxic units. PMID- 21019882 TI - A vibrating muller for the preparation of dispersions of fine pigments for electron microscopy. PMID- 21019883 TI - The amino acid composition of proteins and foods. PMID- 21019884 TI - Amino acids in food materials. PMID- 21019885 TI - Canadian researches on BAL (British anti-lewisite). PMID- 21019886 TI - Thiamine deficiency and high estrogen findings in uterine cancer and in menorrhagia. PMID- 21019887 TI - The antibacterial activity of protamine zinc insulin. PMID- 21019888 TI - A method for determining bacterial resistance and susceptibility to sulfonamides and penicillin. PMID- 21019889 TI - About the chemical nature of syphilis antigen. PMID- 21019890 TI - A cheap and speedy method of cleaning old microscope slides. PMID- 21019891 TI - B-glycoside formation in plants from absorbed chemicals. PMID- 21019892 TI - New use for DDT. PMID- 21019893 TI - Importance of neural fibroblasts in the regeneration of nerve. PMID- 21019894 TI - Vasoparalysis and vasothrombosis of the brain in infancy and in early childhood. PMID- 21019895 TI - Divergence paralysis associated with tumor of the brain. PMID- 21019896 TI - Combat neuroses; development of combat exhaustion. PMID- 21019897 TI - Neurofibromatosis with defect in wall of orbit; report of five cases. PMID- 21019898 TI - Early effects of penicillin treatment of dementia paralytica; a clinical and psychologic study. PMID- 21019899 TI - Pituitary tumors and their treatment. PMID- 21019900 TI - Neurocirculatory asthenia, effort syndrome and anxiety neurosis. PMID- 21019901 TI - Essential male homosexuality and results of treatment. PMID- 21019902 TI - Intracranial aneurysm in fifty-one proved cases. PMID- 21019903 TI - Psychosomatic medicine and psychiatry. PMID- 21019904 TI - Concerning present inadequacies in the legal recognition and handling of the mentally ill. PMID- 21019905 TI - Convulsive shock therapy in an Army general hospital. PMID- 21019906 TI - Myasthenia gravis. PMID- 21019907 TI - Disseminated sclerosis. PMID- 21019908 TI - The brain of the giant panda (Ailuropoda melanoleuca). PMID- 21019909 TI - The human pyramidal tract; a study of the representation of the cortico-spinal components in the spinal cord. PMID- 21019910 TI - The cerebellar nuclear gray in the sparrow (Passer domesticus). PMID- 21019911 TI - The ponto-cerebellar projection in the rabbit and cat; experimental investigations. PMID- 21019912 TI - Effect on the electroencephalogram of localized pressure on the brain. PMID- 21019913 TI - Eye movements following strychninization of the superior colliculus of cats. PMID- 21019914 TI - Synaptic potentials of motoneurones. PMID- 21019915 TI - The pyramidal tract; effect of maximal injury on acid phosphatase content in neurons of cats. PMID- 21019916 TI - A cortico-bulbo-reticular pathway from area 4-s. PMID- 21019917 TI - Pyruvic acid exchange of the brain. PMID- 21019918 TI - Body disproportions and dominant personality traits. PMID- 21019919 TI - A study of personality of normal young men maintained on restricted intakes of vitamins of the B complex. PMID- 21019920 TI - Individual psychotherapy. PMID- 21019922 TI - Hypnotherapy. PMID- 21019921 TI - Narcotherapy. PMID- 21019923 TI - Group psychotherapy. PMID- 21019924 TI - The war blinded; their emotional, social and occupational situation. PMID- 21019925 TI - Treatment of warts by suggestion. PMID- 21019927 TI - [Not Available]. PMID- 21019926 TI - [Not Available]. PMID- 21019928 TI - [Not Available]. PMID- 21019929 TI - [Not Available]. PMID- 21019930 TI - [Not Available]. PMID- 21019931 TI - [Not Available]. PMID- 21019932 TI - [Not Available]. PMID- 21019933 TI - [Not Available]. PMID- 21019934 TI - [Not Available]. PMID- 21019935 TI - [Not Available]. PMID- 21019936 TI - [Not Available]. PMID- 21019937 TI - [Not Available]. PMID- 21019938 TI - [Not Available]. PMID- 21019939 TI - [Not Available]. PMID- 21019940 TI - [Not Available]. PMID- 21019941 TI - [Not Available]. PMID- 21019942 TI - [Not Available]. PMID- 21019943 TI - [Not Available]. PMID- 21019944 TI - [Not Available]. PMID- 21019945 TI - Relation of the eye to immunity in syphilis, with special reference to the pathogenesis of interstitial keratitis. PMID- 21019946 TI - Atopic cataracts; report of four cases. PMID- 21019948 TI - A center for ocular divergence; does it exist? PMID- 21019947 TI - The surgical treatment of strabismus. PMID- 21019949 TI - Periarteritis nodosa with involvement of the choroidal and retinal arteries. PMID- 21019950 TI - Further studies on the use of furmethide in the treatment of glaucoma. PMID- 21019951 TI - Oral penicillin in ocular inflammations. PMID- 21019952 TI - Some methods of lid repair and reconstruction. PMID- 21019953 TI - Report of a case of iridocyclitis associated with chickenpox. PMID- 21019954 TI - Dental acrylic implant for use in evisceration or enucleation of the eyeball. PMID- 21019956 TI - Boeck's sarcoid. PMID- 21019955 TI - Congenital membranous cataract. PMID- 21019957 TI - Melanoma of the skin with ocular and orbital metastases. PMID- 21019958 TI - Thyrotropic exophthalmos. PMID- 21019959 TI - Macular degeneration; a clinical and pathologic study. PMID- 21019960 TI - Multiple nodular tuberculous scleritis. PMID- 21019961 TI - Massive colloid degeneration of the retina. PMID- 21019963 TI - Lipoblastic and megakaryocytoid multiple myeloma. PMID- 21019962 TI - Comparative cytology of Wright's stained smears and histologic sections in multiple myeloma. PMID- 21019964 TI - Giant follicular lymphoblastoma. PMID- 21019965 TI - The use of pectin and gelatin in the processing of plasma in the blood bank. PMID- 21019966 TI - Problems in blood grouping in relation to transfusion. PMID- 21019968 TI - The photoelectric erythrocyte count; clinical application. PMID- 21019967 TI - Resistance of erythrocytes to hemolysis in jaundice. PMID- 21019969 TI - A quantitative macro flocculation test for the serodiagnosis of syphilis. PMID- 21019970 TI - A quantitative fixation of complement test for the diagnosis of syphilis, leptospirosis, echinococcus disease malaria, bacterial and other diseases. PMID- 21019971 TI - A method for grouping and classifying serologic reactions for syphilis based on flocculation and fixation of complement units. PMID- 21019972 TI - Xenopus laevis pregnancy test; report of a series with a small number of frogs. PMID- 21019973 TI - The use of laked blood smears in the early diagnosis of meningococcic infections. PMID- 21019975 TI - Centrifuged agglutination reactions for serum diagnosis and bacterial identification. PMID- 21019974 TI - Steiner's silver stain for spirochetes in tissue sections; a technician's experience. PMID- 21019976 TI - A practical and inexpensive method for fixation of paraffin sections to slides. PMID- 21019977 TI - Penicillin resistance; of bacteria; strain variations in penicillin sensitivity among bacterial species encountered in war wounds and infections. PMID- 21019978 TI - Penicillin resistance; of fungi. PMID- 21019979 TI - Cardiolipin antigen in the microscopic slide precipitation test for syphilis. PMID- 21019980 TI - Fatal Chagas' disease. PMID- 21019981 TI - Klebsiella (Friedlander's bacillus) infections in an Army hospital. PMID- 21019982 TI - The serum agglutination reaction in diagnosis of bacillary dysentery. PMID- 21019983 TI - Gangrene of lower extremity following carbon monoxide asphyxia. PMID- 21019984 TI - The distribution of the nerves to the adult human uterus. PMID- 21019985 TI - Note on the pathology of Morton's metatarsalgia. PMID- 21019986 TI - Mycetoma pedis; case report. PMID- 21019987 TI - Diagnosis of erythroblastosis (hemolytic anemia) in the macerated fetus. PMID- 21019988 TI - Hypertension and necrotizing arteritis in the rat following renal infarction. PMID- 21019989 TI - An analysis of the Klippel-Feil syndrome. PMID- 21019990 TI - Ovarian involvement in Hodgkin's disease. PMID- 21019991 TI - Plasmodium falciparum malaria; the coronary and myocardial lesions observed at autopsy in two cases of acute fulminating P. falciparum infection. PMID- 21019992 TI - Reticulum. PMID- 21019993 TI - Role of stasis in the development of pulmonary infarcts. PMID- 21019994 TI - Intestinal perforation in paratyphoid due to Salmonella paratyphi B. PMID- 21019995 TI - An acute febrile illness characterized by thrombopenic purpura, hemolytic anemia and generalized platelet thrombosis. PMID- 21019996 TI - Epidermoid carcinoma arising in an endometrial cyst of the ovary. PMID- 21019997 TI - Physiology and functional pathology of the lymphatic system applied to allergy of the nose and paranasal sinuses. PMID- 21019998 TI - The volumetric incidence of atmospheric allergens; rate of fall of pollen grains in still air. PMID- 21019999 TI - The volumetric incidence of atmospheric allergens; a proposed standard method of gravity sampling, counting, and volumetric interpolation of results. PMID- 21020000 TI - Survey of broncial asthma in soldiers; bronchoscopic findings and incidence of respiratory infection. PMID- 21020001 TI - Allergy in the Pacific. PMID- 21020002 TI - Ethyl-nor-epinephrine by inhalation for bronchial asthma; a comparison with epinephrine. PMID- 21020003 TI - Contact dermatitis due to ace adherent. PMID- 21020004 TI - Behavior problems in children. PMID- 21020005 TI - Outlines for well baby clinics; recording development of the first twelve months. PMID- 21020006 TI - Multiple sclerosis in childhood. PMID- 21020007 TI - Congenital biliary cirrhosis. PMID- 21020008 TI - Pathologic study of the acutely inflamed human pharynx in influenza A infection. PMID- 21020009 TI - Histoplasmosis in infancy. PMID- 21020010 TI - Pontine tumors in infancy. PMID- 21020011 TI - [Not Available]. PMID- 21020013 TI - [Not Available]. PMID- 21020012 TI - [Not Available]. PMID- 21020014 TI - [Not Available]. PMID- 21020015 TI - [Not Available]. PMID- 21020016 TI - On the treatment of influenzal meningitis by sulfa preparations. PMID- 21020017 TI - [Not Available]. PMID- 21020018 TI - [Not Available]. PMID- 21020019 TI - [Not Available]. PMID- 21020021 TI - [Not Available]. PMID- 21020020 TI - [Not Available]. PMID- 21020022 TI - [Not Available]. PMID- 21020023 TI - [Not Available]. PMID- 21020024 TI - [Not Available]. PMID- 21020025 TI - [Not Available]. PMID- 21020026 TI - [Not Available]. PMID- 21020027 TI - Metastatic osteomyelitis following mastoiditis. PMID- 21020028 TI - Atelectasis in infancy and childhood. PMID- 21020029 TI - Rupture of the kidney. PMID- 21020030 TI - The movement in medical economics. PMID- 21020031 TI - Facts and figures in pediatric medicine. PMID- 21020032 TI - Streptomycin; a summary of clinical and experimental observations. PMID- 21020033 TI - Histoplasmosis; a report of four cases, two in siblings; histoplasmin test and other diagnostic procedures. PMID- 21020034 TI - Rheumatic recrudescences; diagnosis and prevention. PMID- 21020035 TI - The pediatrician's responsibilities in the diagnosis and treatment of early poliomyelitis. PMID- 21020036 TI - The relationship of infantile paralysis epidemics to community resources in the treatment of patients. PMID- 21020037 TI - The role of physical medicine in poliomyelitis. PMID- 21020038 TI - The psychologic and psychiatric implication of poliomyelitis. PMID- 21020039 TI - Child welfare work in Brazil. PMID- 21020040 TI - Certain peripheral and central nervous system effects of beta-diethylaminoethyl phenyl-alphathienylglycolate HCl and pharmacologically related compounds. PMID- 21020041 TI - Studies on the phaarmacology of DDT (2,2 bis-(parachlorphenyl)-l,l,l trichloroethane); the acute toxicity of DDT following intravenous injection in mammals with observations on the treatment of acute DDT poisoning. PMID- 21020042 TI - Studies on the pharmacology of DDT (2,2,bis-parachlorphenyl-l,l,l trichloroethane); the sensitization of the myocardium to sympathetic stimulation during acute DDT intoxication. PMID- 21020043 TI - The anti-histamine properties of benadryl, beta-di-methylaminoethyl benzhydryl ether hydrochloride. PMID- 21020044 TI - Studies on the fate of nicotine in the body; observations on the chemical structure of an end product of nicotine metabolism. PMID- 21020046 TI - On the elimination of g-strophanthin by the rat. PMID- 21020045 TI - Effects of morphine and its derivatives on intermediary metabolism; the influence of chronic morphine and heroin poisoning on the oxygen consumption of dog, rat and mouse skeletal muscle. PMID- 21020047 TI - The effect of some acridine compounds on the growth and respiration of E. coli. PMID- 21020048 TI - The absorption of sulphonamides in mice. PMID- 21020049 TI - The antimalarial action in ducks of certain sulfanilamide derivatives. PMID- 21020050 TI - Acute toxicity of vasopressor amines; effect of temperature. PMID- 21020051 TI - Acute toxicity of vasopressor amines; comparative data. PMID- 21020053 TI - The rate of disappearance of a marihuana-active substance from the circulating blood. PMID- 21020052 TI - Relation of absorbability to the comparative toxicity of DDT for insects and mammals. PMID- 21020054 TI - Further studies on the depressant actions of barbiturates on the terrapin cardiac vagus nerve. PMID- 21020055 TI - Behavior of synthetic esters of strophanthidin, the acetate, propionate, butyrate, and benzoate, in man. PMID- 21020056 TI - [Not Available]. PMID- 21020057 TI - Psychological services in the Veterans Administration. PMID- 21020058 TI - Veterans' guidance centers; a survey of their problems and activities. PMID- 21020059 TI - Counseling in the rehabilitation service. PMID- 21020061 TI - STANDARDS for clinical psychologists in the Federal Government. PMID- 21020060 TI - Employment counseling program of the United States Employment Service. PMID- 21020062 TI - College and university procedures in the reorientation of veterans. PMID- 21020063 TI - Rehabilitation of the newly blinded. PMID- 21020064 TI - Interrelationship of clinical psychology and psychiatry. PMID- 21020065 TI - Clinical counseling in emotional and social rehabilitation. PMID- 21020066 TI - Four psychometric techniques useful in vocational guidance. PMID- 21020067 TI - Range of interests and psychopathologies. PMID- 21020068 TI - A method of analysis for the thematic apperception test and autobiography. PMID- 21020069 TI - A method of treatment for nocturnal enuresis. PMID- 21020071 TI - Error redundant; a reply to the Error in psychiatry. PMID- 21020070 TI - Directive psychotherapy; imparting psychological information. PMID- 21020072 TI - Opportunities for international health activities. PMID- 21020073 TI - Bacteriologic procedures in the evaluation of methods for control of air-borne infection. PMID- 21020074 TI - MICROBIOLOGICAL examination of foods; tentative methods for the microbiological examination of frozen foods. PMID- 21020075 TI - Selective Service rejection statistics and some of their implications. PMID- 21020076 TI - Chronic disease; a problem that must be faced. PMID- 21020077 TI - In-service training in a State department of health. PMID- 21020078 TI - Health education. PMID- 21020079 TI - Infectious hepatitis, presumedly food-borne outbreak. PMID- 21020080 TI - Pertussis vaccine prepared with phaseI cultures grown in fluid medium. PMID- 21020081 TI - The public health nurse in the department of health. PMID- 21020082 TI - State variation in the collection of reportable disease statistics. PMID- 21020083 TI - Disinfection of air by germicidal vapors and mists. PMID- 21020084 TI - The present status of vaccination against influenza. PMID- 21020085 TI - Seeing is believing in sanitary control. PMID- 21020086 TI - A study of nutritional conditions in a group of urban children. PMID- 21020087 TI - Phenothiazine in the treatment of enterobiasis. PMID- 21020089 TI - Scope of geriatrics in Connecticut. PMID- 21020088 TI - Use of topical fluorine on school age children and its effect on dental caries. PMID- 21020090 TI - Rheumatic fever; sulfadiazine for the prevention of recurrences. PMID- 21020091 TI - Divorces in Connecticut, 1935-1944. PMID- 21020092 TI - The growth and health of children. PMID- 21020093 TI - The development of health education. PMID- 21020094 TI - RE-INOCULATION of school children against diphtheria. PMID- 21020095 TI - Diphtheria immunization circulars 193 and 194, 1945. PMID- 21020096 TI - The Rh factor and its significance. PMID- 21020097 TI - Further note on the wartime growth of schoolchildren. PMID- 21020098 TI - The influence of war conditions on bovine tuberculosis in man in Amsterdam. PMID- 21020099 TI - The evolution of ideas on continued fever. PMID- 21020100 TI - Local and central health administration. PMID- 21020101 TI - The cancer problem in New Jersey. PMID- 21020102 TI - Investigation of an outbreak of typhoid fever in a summer hotel. PMID- 21020103 TI - Compulsory versus voluntary methods in venereal disease control. PMID- 21020104 TI - Cerebrospinal meningitis; a chronological record of reported cases and deaths. PMID- 21020105 TI - Some physical properties of DDT and certain derivatives. PMID- 21020106 TI - TEAMWORK in tuberculosis control. PMID- 21020107 TI - Geographic differences in sensitivity to histoplasmin among student nurses. PMID- 21020108 TI - Tuberculosis mortality in the United States and in each state; 1944. PMID- 21020109 TI - A method of conducting the 50 percent hemolysis end point complement-fixation test for parasitic diseases. PMID- 21020110 TI - Streptomycin in experimental plague. PMID- 21020111 TI - Sequestration of calcium and magnesium in the presence of alkaline detergents. PMID- 21020112 TI - [Not Available]. PMID- 21020113 TI - [Not Available]. PMID- 21020114 TI - [Not Available]. PMID- 21020115 TI - [Not Available]. PMID- 21020116 TI - [Not Available]. PMID- 21020117 TI - [Not Available]. PMID- 21020118 TI - [Not Available]. PMID- 21020119 TI - [Not Available]. PMID- 21020120 TI - [Not Available]. PMID- 21020121 TI - [Not Available]. PMID- 21020122 TI - [Not Available]. PMID- 21020123 TI - [Not Available]. PMID- 21020124 TI - [Not Available]. PMID- 21020125 TI - [Not Available]. PMID- 21020126 TI - [Not Available]. PMID- 21020127 TI - [Not Available]. PMID- 21020129 TI - THE Golden Age of child health. PMID- 21020128 TI - [Not Available]. PMID- 21020130 TI - LARGE decline in mortality from degenerative diseases. PMID- 21020131 TI - [Not Available]. PMID- 21020132 TI - [Not Available]. PMID- 21020133 TI - [Not Available]. PMID- 21020134 TI - Correlation of gastroscopic, roentgenologic and pathologic findings in diseases of the stomach; an analysis of 245 proved cases. PMID- 21020135 TI - Spondylolisthesis; criteria for more accurate diagnosis of true anterior slip of the involved vertebral segment. PMID- 21020136 TI - Lumbosacral roentgenograms of one hundred soldiers; a control study. PMID- 21020137 TI - Osteomyelitis in infants. PMID- 21020138 TI - The occasional appearance of both inner and outer suture lines in roentgenograms of the skull simulating fissure fracture. PMID- 21020139 TI - Duplication of the entire large intestine (colon duplex); report of case. PMID- 21020140 TI - Clubbed fingers. PMID- 21020141 TI - Congenital dislocation of the hip; report of case. PMID- 21020142 TI - Giant jugular fossa; with brief notes on the anatomical variations of the jugular fossa. PMID- 21020143 TI - Present status of roentgen therapy of hyperthyroidism and related endocrine disturbances. PMID- 21020144 TI - Pneumothorax in young adult males. PMID- 21020145 TI - Elements of roentgen technique; the universal distinctor of Holzknecht-Ingber in the examination of the gastrointestinal tract. PMID- 21020146 TI - Improved technique for bronchograms. PMID- 21020147 TI - [Not Available]. PMID- 21020148 TI - [Not Available]. PMID- 21020149 TI - [Not Available]. PMID- 21020150 TI - [Not Available]. PMID- 21020151 TI - [Not Available]. PMID- 21020152 TI - [Not Available]. PMID- 21020153 TI - [Not Available]. PMID- 21020155 TI - [Not Available]. PMID- 21020154 TI - [Not Available]. PMID- 21020156 TI - [Not Available]. PMID- 21020157 TI - [Not Available]. PMID- 21020158 TI - [Not Available]. PMID- 21020159 TI - [Not Available]. PMID- 21020160 TI - [Not Available]. PMID- 21020161 TI - [Not Available]. PMID- 21020162 TI - Some aspects of radiography of the lumbo-sacral region. PMID- 21020163 TI - A new principle in roentgenography of the lateral lumbar spine. PMID- 21020164 TI - An additional technique for the demonstration of the cervical and upper thoracic spine in a lateral position. PMID- 21020165 TI - X-ray protection for patient and operator. PMID- 21020166 TI - Radiography of the knee for internal derangement. PMID- 21020167 TI - The psychological and technical handling of children in the radiographic department. PMID- 21020168 TI - The sphenoidal fissure; anatomic and radiographic study. PMID- 21020169 TI - Urinary calculi in recumbent fracture patients. PMID- 21020170 TI - Splenectomy for trauma; practical points in surgical technic. PMID- 21020171 TI - Complete duodenal obstruction in the newborn. PMID- 21020172 TI - Non-eclamptic late toxemias treated by vitamin E. PMID- 21020173 TI - Primary malignant tumors of the spleen, with special reference to endotheliomas. PMID- 21020174 TI - Surgical correction of chin malformations. PMID- 21020175 TI - Primary resection of malignant lesions of the large bowel. PMID- 21020176 TI - Gastroduodenal invagination due to a submucous lipoma of the stomach. PMID- 21020177 TI - Varicose veins; ten years' observations on treatment. PMID- 21020178 TI - Orchiectomy in the treatment of carcinoma of the prostate. PMID- 21020179 TI - Desiccation of residual red blood cells from plasma production. PMID- 21020180 TI - Acromioclavicular joint injuries; a modified conservative form of treatment. PMID- 21020181 TI - Mean disposition of tibial shaft fractures. PMID- 21020182 TI - The venous circulation is audible throughout the system and in fibroid uteri. PMID- 21020183 TI - Cavernous hemangioma of the spleen. PMID- 21020184 TI - Obturator hernia; report of an operation for irreducible incarceration. PMID- 21020185 TI - Splenosis; intraperitoneal transplants following traumatic rupture of the spleen. PMID- 21020186 TI - Mediastinal emphysema; report of three cases secondary to neck operations. PMID- 21020187 TI - Volvulus of the sigmoid colon. PMID- 21020188 TI - Rupture of the deep epigastric vessels. PMID- 21020189 TI - Desmoid of the anterior chest wall. PMID- 21020190 TI - Osteoid osteoma. PMID- 21020191 TI - Surgical hospital. PMID- 21020192 TI - Evolution of surgery. PMID- 21020193 TI - Vascular injuries of the extremities in battle casualties. PMID- 21020194 TI - Penetrating head wounds; experiences from the Italian campaign. PMID- 21020195 TI - Treatment of jaw and face casualties in the British Army. PMID- 21020197 TI - Pulmonary embolism; a statistical study with particular reference to the value of certain preventive measures. PMID- 21020196 TI - Repair of soft-tissue war wounds. PMID- 21020198 TI - Congenital cystic lung; successful pneumonectomy in a three-week-old baby. PMID- 21020199 TI - Delayed internal fixation of compound battle fractures in the Mediterranean theater of operations; case histories with illustrations; a follow-up study in the zone of the interior. PMID- 21020200 TI - The surgical significance of the accessory spleen. PMID- 21020201 TI - Biliary ascariasis; report of 19 cases. PMID- 21020202 TI - Sympathectomy for ischemia following femoral artery ligation. PMID- 21020203 TI - Fibrosarcoma protuberans arising on an old burn scar. PMID- 21020204 TI - Intestinal obstruction due to persistence of the omphalomesenteric artery. PMID- 21020205 TI - Abdominopelvic sympathectomy for relief of pain of cancer of the cervix. PMID- 21020206 TI - Preoperative diagnosis of recent wounds of the abdomen. PMID- 21020207 TI - Cetylpyridinium chloride as a cutaneous germicide in major surgery; a comparative study. PMID- 21020208 TI - Synthetic adhesives in the treatment of wounds of the liver and other surgical conditions. PMID- 21020209 TI - Gunshot wound of the thoracic esophagus; report of a case. PMID- 21020210 TI - Toxemia syndrome after burns; biochemical and pathologic observations and studies. PMID- 21020211 TI - PROGRESS in orthopedic surgery for 1944; a review prepared by an editorial board of the American Academy of Orthopaedic Surgeons. PMID- 21020212 TI - Review of urologic surgery. PMID- 21020213 TI - Physiological and clinical action of curare. PMID- 21020214 TI - Spinal anesthesia for operation on the vertebral column. PMID- 21020215 TI - Continuous lumbar anesthesia with dilution technique. PMID- 21020216 TI - Pentothal sodium in tonsillectomy anesthesia. PMID- 21020217 TI - Anesthetic procedures used in a general hospital in the communication zone with analysis of 2,000 anesthetics. PMID- 21020218 TI - A simplified technique for spinal anesthesia using nupercaine. PMID- 21020219 TI - Low spinal anesthesia in obstetrics in the Indianapolis City Hospital. PMID- 21020220 TI - Psychosomatic problems in military orthopaedic surgery. PMID- 21020221 TI - Circumferential hypalgesia (stocking-and-glove anesthesia). PMID- 21020222 TI - Pathomechanics of the hip after the shelf operation. PMID- 21020223 TI - Early secondary closure following saucerization for chronic infection of bone; a preliminary report. PMID- 21020224 TI - Intertrochanteric fractures and fractures of the neck of the femur; a guide and a method of procedure for accurate placement of a nail. PMID- 21020226 TI - Experience with capsulorrhaphy for recurrent dislocation of the shoulder. PMID- 21020225 TI - A simplification of Bankart's capsulorrhaphy for recurrent dislocation of the shoulder. PMID- 21020227 TI - Rotation osteotomy; a method employed in cases of congenital club-foot. PMID- 21020228 TI - Deformities following surgical epiphyseal arrest. PMID- 21020229 TI - Lag-screw fixation in fractures of the tibial tuberosity. PMID- 21020230 TI - Allergy of joints. PMID- 21020231 TI - Development of squamous-cell carcinomata in the sinus tracts of chronic osteomyelitis. PMID- 21020232 TI - Fixation of the transplanted tibial tubercle. PMID- 21020233 TI - Biochemical changes in the fracture hematoma. PMID- 21020234 TI - Sarcoid of bone. PMID- 21020235 TI - Spasmodic torticollis; severe organic type treated by combined operation, rhizotomy, and fusion. PMID- 21020236 TI - Intramedullary pinning of diaphyseal fractures. PMID- 21020237 TI - Reconstructive surgery in patients with war fractures of the ankle and foot. PMID- 21020238 TI - The use of pedicled muscle flaps in the surgical treatment of chronic osteomyelitis resulting from compound fractures. PMID- 21020239 TI - Condylar movement in the study of internal derangement of the temporomandibular joint. PMID- 21020240 TI - A review of the inception and development of a type of reparative surgery adapted to bodily mechanics. PMID- 21020241 TI - Bone-marrow embolism following fracture. PMID- 21020242 TI - Bilateral extra-articular ankylosis of the hip joint. PMID- 21020243 TI - A bilateral anomaly of the wrist. PMID- 21020244 TI - Fracture-dislocation of the mid-tarsal and cuboideonavicular joints. PMID- 21020245 TI - Avulsion of the ischial tuberosity. PMID- 21020247 TI - Submeniscal foreign bodies in the knee; report of two cases. PMID- 21020246 TI - Isolated fracture of the pisiform bone. PMID- 21020248 TI - Splint for the treatment of mallet finger. PMID- 21020249 TI - An improved pedal for electrical apparatus used in surgery. PMID- 21020250 TI - Splint to correct deformity resulting from injury to ulnar nerve. PMID- 21020251 TI - Infection of the knee joint by Clostridium welchii. PMID- 21020252 TI - Pseudoarthrosis of the tibia and fibula in children. PMID- 21020253 TI - Fusion of the spine after removal of ruptured disk. PMID- 21020254 TI - Osteotomy for the treatment of ununited fracture of the femoral neck. PMID- 21020255 TI - Bone grafts for ununited fracture of the neck of the femur; a report of ninety cases. PMID- 21020256 TI - Late complications in fracture of the neck of the femur treated by nailing, bone grafting or both. PMID- 21020257 TI - Arthroplasty for congenital dislocation of the hip. PMID- 21020258 TI - Replacement of lower end of femur or upper end of tibia. PMID- 21020259 TI - Malignant tumors of bone. PMID- 21020261 TI - Principles of cineplastic operations. PMID- 21020260 TI - An appeal for a more radical attitude in the treatment of bone cysts and giant cell tumors. PMID- 21020262 TI - Operations on the bodies of the vertebrae. PMID- 21020263 TI - Osteoid-osteoma of cervical spinous process. PMID- 21020264 TI - Orthopedic measures for use in irreparable nerve injury. PMID- 21020265 TI - Pseudoarthrosis of the neck of the femur. PMID- 21020266 TI - Enabling useless thigh-stumps to move a prothesis. PMID- 21020267 TI - Screw fixation of fractures. PMID- 21020269 TI - Patella fracture; a method of treatment. PMID- 21020270 TI - [Not Available]. PMID- 21020268 TI - Congenital dislocation of the hip; fifty year survey. PMID- 21020271 TI - [Not Available]. PMID- 21020272 TI - [Not Available]. PMID- 21020273 TI - [Not Available]. PMID- 21020274 TI - [Not Available]. PMID- 21020275 TI - [Not Available]. PMID- 21020276 TI - [Not Available]. PMID- 21020277 TI - [Not Available]. PMID- 21020278 TI - [Not Available]. PMID- 21020279 TI - [Not Available]. PMID- 21020280 TI - [Not Available]. PMID- 21020281 TI - [Not Available]. PMID- 21020282 TI - [Not Available]. PMID- 21020283 TI - [Not Available]. PMID- 21020284 TI - [Not Available]. PMID- 21020285 TI - [Not Available]. PMID- 21020286 TI - [Not Available]. PMID- 21020288 TI - [Not Available]. PMID- 21020287 TI - [Not Available]. PMID- 21020289 TI - [Not Available]. PMID- 21020290 TI - [Not Available]. PMID- 21020291 TI - Preoperative dietary management for surgical patients; with special reference to lesions of the stomach and duodenum. PMID- 21020292 TI - Alkaline phosphatase and metastatic liver disease. PMID- 21020293 TI - Pulsating hematoma, false aneurysm, and arteriovenous fistula due to war injuries. PMID- 21020294 TI - Causalgia secondary to injury of the major peripheral nerves; treatment by sympathectomy. PMID- 21020295 TI - Gunshot wounds of the abdomen; a review of 149 cases. PMID- 21020296 TI - Acute pulmonary edema associated with mediastinal emphysema. PMID- 21020297 TI - Venous interruption in thromboembolic disease. PMID- 21020298 TI - Principles in reparative plastic surgery; experiences in a general hospital in the tropics. PMID- 21020299 TI - The coagulum contact method (Sano) of skin grafting in the treatment of burns and wounds. PMID- 21020300 TI - The plastic correction of superficial vascular and pigmented nevi. PMID- 21020301 TI - Rayon, an ideal surgical dressing for surface wounds. PMID- 21020302 TI - The use of saline solution, glycerin, and acetic acid in the care of burns; an odorless method of treating burns. PMID- 21020303 TI - The use of acetic acid-glycerin-saline solution in skin grafting. PMID- 21020304 TI - Use of rectus sheath and superior pubic ligament in direct and recurrent inguinal hernia. PMID- 21020305 TI - Carcinoma of the stomach; a ten-year survey made in a general hospital. PMID- 21020306 TI - Splenorenopexy in essential hypertension; report of three cases. PMID- 21020307 TI - Paroxysmal hypertension due to adrenal medullary tumor (pheochromocytoma). PMID- 21020308 TI - Surgical observations in the tropics. PMID- 21020309 TI - Penetrating wounds of the head. PMID- 21020310 TI - Wartime neurosurgical experiences. PMID- 21020312 TI - Causes of amputations in battle casualties with emphasis on vascular injuries. PMID- 21020311 TI - Anaerobic infection and gangrene of war wounds in casualties from the Philippine Islands. PMID- 21020313 TI - A combination arm splint and needle-holder device. PMID- 21020314 TI - Hits, strikes and outs in the use of pedicle flaps for nasal restoration or correction. PMID- 21020315 TI - Observations on the treatment of adenocarcinoma of the uterus. PMID- 21020316 TI - Practical observations on the copper sulfate method for determining the specific gravities of whole blood and serum. PMID- 21020317 TI - Lumbar appendicitis and lumbar appendectomy. PMID- 21020318 TI - Correction of blood loss during surgical operations. PMID- 21020319 TI - Patellectomy in the military service; a report of 19 cases. PMID- 21020320 TI - Bronchopneumonia following ether anesthesia in obstetrics. PMID- 21020321 TI - The retrograde lymphatic spread of carcinoma of the rectosigmoid region; its influence on surgical procedures. PMID- 21020322 TI - Rectal strictures due to lymphogranuloma venereum; with especial reference to Pauchet's excision operation. PMID- 21020323 TI - Ligation of the innominate artery for innominate aneurysm using rubber bands; report of a case. PMID- 21020324 TI - Failure of the urogenital union. PMID- 21020325 TI - Preliminary report of a method for the prevention of leakage of intestinal anastomoses. PMID- 21020326 TI - Utilization of Henle's ligament, iliopubic tract, aponeurosis transversus abdominis and Cooper's ligament in inguinal herniorrhaphy; a report of 162 consecutive cases. PMID- 21020327 TI - Early postoperative rising; a statistical study of hospitals complications. PMID- 21020328 TI - Restoration of continuity versus cure in carcinoma of the rectum. PMID- 21020329 TI - An operation for the correction of flexible flat feet of adolescents. PMID- 21020330 TI - Infiltrating benign lipomas of the extremities. PMID- 21020331 TI - Further studies in the use of sigmodal in obstetrical analgesia and amnesia. PMID- 21020332 TI - Menstrual dysfunctions; the climacteric. PMID- 21020333 TI - Medical journals in Oregon. PMID- 21020334 TI - Bilateral adrenal medullary hemorrhages (adrenal apoplexy). PMID- 21020335 TI - Medical research in the postwar world. PMID- 21020336 TI - Two new species of rat mites (Neoschongastia spp.) from a focus of scrub typhus on Mindoro, Philippine Islands. PMID- 21020337 TI - Clinical and laboratory variation of virulence in scrub typhus. PMID- 21020338 TI - Experimental studies with Bullis fever. PMID- 21020339 TI - A neurotropic virus isolated from Aedes mosquitoes caught in the Semliki forest. PMID- 21020340 TI - Medical shock in the pathogenesis of algid malaria. PMID- 21020341 TI - An outline for teaching mosquito stomach and salivary gland dissection. PMID- 21020342 TI - Tsutsugamushi disease (scrub or mite-borne typhus) in the Philippine Islands during American re-occupation in 1944-45. PMID- 21020344 TI - A method of rearing chigger mites (Acarina, Trombiculinae). PMID- 21020343 TI - A contribution to our knowledge of the bionomics of the common North American chigger, Eutrombicula alfred-dugesi (Oudemans) with a description of a rapid collecting method. PMID- 21020345 TI - [Not Available]. PMID- 21020346 TI - [Not Available]. PMID- 21020347 TI - [Not Available]. PMID- 21020348 TI - [Not Available]. PMID- 21020349 TI - [Not Available]. PMID- 21020350 TI - Exoerythrocytic forms of Plasmodium lophurae in turkeys. PMID- 21020351 TI - The kwashiorkor syndrome. PMID- 21020352 TI - Teaching of tropical medicine. PMID- 21020353 TI - Autoantigens and autoantibodies in the pathogenesis of disease with special refenence to blackwater fever. PMID- 21020354 TI - Postmortem femoral bone marrow studies of kala-azar. PMID- 21020355 TI - A further biochemical study of the blood of cholera patients. PMID- 21020356 TI - A field experiment on the prophylactic value of pentamidine in sleeping sickness. PMID- 21020357 TI - Ainhum; a clinical summary of forty-five cases on the Isthmus of Panama. PMID- 21020359 TI - Habituation of Pulex irritans to animal host. PMID- 21020358 TI - Tick-typhus in Abyssinia. PMID- 21020360 TI - Kala-azar. PMID- 21020361 TI - Yellow fever in West Africa, 1942. PMID- 21020362 TI - Spirometric and bronchospirometric studies in thoracoplasty. PMID- 21020363 TI - Spread of tuberculosis in families of tuberculous patients. PMID- 21020364 TI - Community organization for mass chest x-ray surveys. PMID- 21020365 TI - The St. Louis County tuberculosis survey. PMID- 21020366 TI - The combined action of p,p-diaminodiphenylsulfone and immunization in experimental tuberculosis. PMID- 21020367 TI - Derivatives of p,p-diaminodiphenylsulfone and sulfanilamide in experimental tuberculosis. PMID- 21020368 TI - Tubercle bacilli in the metabolic apparatus. PMID- 21020369 TI - Tuberculosis in Sweden and the fight against it in recent years. PMID- 21020370 TI - Artificial pneumothorax in patients with high blood sedimentation rate. PMID- 21020371 TI - Tuberculosis of skeleton and lung combined; prognosis and treatment. PMID- 21020372 TI - Extrapleural pneumothorax. PMID- 21020373 TI - Mass x-ray of pregnant women. PMID- 21020374 TI - Trimethylene-glycol-phenol mixture for rapid staining of the tubercle bacillus. PMID- 21020375 TI - Experiences in the management of congenital anomaly of the kidney in the Army. PMID- 21020376 TI - Sclerosing injection of polycystic kidney following surgical exposure. PMID- 21020377 TI - Osteonephropathy; a report of two cases. PMID- 21020378 TI - Acute toxic nephrosis due to poisoning by carbon tetrachloride; a case report. PMID- 21020379 TI - Hemangioma of the kidney; report of an additional case. PMID- 21020380 TI - Migration of foreign bodies with report of case of migration of a shell fragment into the bladder. PMID- 21020381 TI - Traumatic rupture of urinary bladder in an infant 3 1/2 months old with recovery. PMID- 21020382 TI - Infiltrating carcinoma of the bladder; relation of depth of penetration of the bladder wall to incidence of local extension and metastases. PMID- 21020383 TI - Tumor of the testicle; analysis of one hundred cases; a preliminary report. PMID- 21020384 TI - The metabolism of the prostate; transamination and citric acid. PMID- 21020385 TI - Report of two cases of double urethra in the male. PMID- 21020386 TI - Foreign bodies in urethra; six-penny nails present for 12 years. PMID- 21020387 TI - Anomalies of the urachus; persistent fetal bladder. PMID- 21020388 TI - Observations on urinary dysfunction after excision of the rectum. PMID- 21020389 TI - The treatment of Bacillus proteus infections with NU-445. PMID- 21020390 TI - Aerobic actinomyces in urine; preliminary report. PMID- 21020391 TI - Penicillin treatment of urinary infections caused by pyogenic cocci; a report of 101 cases. PMID- 21020392 TI - The influence of diagnostic methods on the gonorrhea rage in the Army Air Forces; experience of the troop carrier command in prediagnostic culture of the gonococous. PMID- 21020393 TI - Management of prostatc surgery in the aged. PMID- 21020394 TI - Ureteral-injury prevention. PMID- 21020395 TI - A contribution to the endocrine aspect of the impotence problem; a report of thirty-nine cases. PMID- 21020396 TI - Complete retention of urine in infancy; a common cause. PMID- 21020397 TI - The diagnosis and clinical course of mycoses produced by the fungus Epidermophyton (Trichophyton) rubrum. PMID- 21020398 TI - Highlights of the Conference in Tropical Dermatology for American Doctors, Mexico City, August 6-18, 1945. PMID- 21020400 TI - ASCETIC ideal and how it corrupts. PMID- 21020399 TI - Tattoo. PMID- 21020401 TI - TABOO and the effect of its survival. PMID- 21020402 TI - INCIDENCE of syphilis during the 17th century. PMID- 21020403 TI - WHO should be sterilized? PMID- 21020404 TI - The treatment of infective arthritis with special reference to hyperthermia. PMID- 21020405 TI - The practical advantages of the Laughlen test for the diagnosis of syphilis. PMID- 21020406 TI - Sociological and psychological factors in venereal disease. PMID- 21020407 TI - The prevention of syringe-transmitted hepatitis. PMID- 21020408 TI - The one-man clinic. PMID- 21020409 TI - Cooperation of health officers and police departments. PMID- 21020410 TI - Preliminary report evaluating the worth of obtaining names of suspected contacts during a regular contact interview. PMID- 21020411 TI - Oral and parenteral use of aluminum penicillin mixtures in the treatment of gonorrhea. PMID- 21020412 TI - Penicillin in the treatment of bovine mastitis. PMID- 21020413 TI - Studies in pullorum disease; the possible relationship of non-specific reactions to the sensitizing influence of ingested proteins. PMID- 21020414 TI - The incidence of erythroleucosis following inoculation by various routes. PMID- 21020415 TI - The concentration penicillin in fore milk following intramammary infusion for the treatment of mastitis. PMID- 21020416 TI - Remarks on the distribution of diseases of the respiratory, circulatory, and haemopoietic systems among domesticated animals. PMID- 21020417 TI - A case of canine S. typhimurium infection with notes on other Salmonella infections in animals. PMID- 21020418 TI - WORK of the Army Veterinary Services in relation to military diary farms in India. PMID- 21020419 TI - A comparative study of the quality of ghee from cow and buffalo under uniform dietary conditions, including heavy feeding of cotton seed. PMID- 21020420 TI - Some observations on wah of goats and sheep in Sind. PMID- 21020421 TI - Salmonellosis in ducks in Army development farm. PMID- 21020422 TI - Duck-rearing at the Livestock Research Station, Hosur Cattle Farm. PMID- 21020423 TI - Carbon tetrachloride in a nematode infestation in a horse. PMID- 21020425 TI - Soluseptasine ointment in Bursati. PMID- 21020424 TI - A combined infection of trypanosomes and Theileria mutans in a stud bull. PMID- 21020426 TI - A case of haemorrhagic septicaemia in an elephant. PMID- 21020427 TI - Penicillin dosage and blood levels for horses. PMID- 21020429 TI - Breast development in an aged male monkey. PMID- 21020428 TI - Orchitis in swine due to Brucella suis. PMID- 21020430 TI - Trypanosoma equiperdum antigen for complement fixation; preparation and titration. PMID- 21020431 TI - SCOFFING at bovine tuberculosis eradication. PMID- 21020432 TI - The teaching of veterinary anatomy. PMID- 21020433 TI - Metrazol in small animal surgery. PMID- 21020434 TI - Intussusception of the stomach of a dog. PMID- 21020437 TI - The role of disinfection in veterinary medicine; sterilization of surgical instruments. PMID- 21020436 TI - A technique of heart puncture in the chicken for obtaining blood. PMID- 21020435 TI - A technique for castrating dogs. PMID- 21020438 TI - Ethylene-oxygen anesthesia. PMID- 21020439 TI - Preliminary tests with DDT for single-treatment eradication of the swine louse, Haematopinus suis. PMID- 21020440 TI - TETANUS in an elephant. PMID- 21020441 TI - Strychnine poisoning. PMID- 21020442 TI - Treatment of stiff lambs with wheat germ oil. PMID- 21020443 TI - A transmissible gastroenteritis in pigs. PMID- 21020444 TI - Recent studies on the treatment of infectious sinusitis in turkeys. PMID- 21020445 TI - CYANOGENIC FORAGE. PMID- 21020446 TI - LAMENESS in swine. PMID- 21020447 TI - Infectious pleuropneumonia of the goat. PMID- 21020448 TI - The horses of the surrendered enemy in Austria. PMID- 21020449 TI - Administrative history of the Veterinary and Remount Branch, 21st Army Group, on the continent. PMID- 21020450 TI - THE Army Veterinary Service in South-East Asia Command. PMID- 21020451 TI - Lentin in veterinary medicine; a review. PMID- 21020452 TI - Penicillin in the treatment of blackleg. PMID- 21020453 TI - Prolapse of the vagina. PMID- 21020454 TI - The normal blood count of the domestic cat. PMID- 21020455 TI - [Not Available]. PMID- 21020456 TI - [Not Available]. PMID- 21020457 TI - [Not Available]. PMID- 21020458 TI - [Not Available]. PMID- 21020459 TI - [Not Available]. PMID- 21020460 TI - [Not Available]. PMID- 21020461 TI - [Not Available]. PMID- 21020462 TI - [Not Available]. PMID- 21020463 TI - [Not Available]. PMID- 21020464 TI - [Not Available]. PMID- 21020465 TI - [Not Available]. PMID- 21020466 TI - Penicillin treatment of acute equine infectious anemia. PMID- 21020467 TI - A practitioner's evaluation of modern therapy in the treatment, control and eradication of bovine mastitis. PMID- 21020468 TI - The relationship of vitamin C to wound healing. PMID- 21020469 TI - Homoplastic osteoma of frontal bone of mule. PMID- 21020470 TI - Gastroenteritis due to drinking kerosene. PMID- 21020471 TI - Surgical repair of teat lacerations. PMID- 21020472 TI - Operation for closed teat sphincter. PMID- 21020473 TI - Proof of the existence of pre-oviposital embryonic deaths in chickens and their bearing on the relation between fertility and hatchability. PMID- 21020474 TI - A revision of the family Acaridae (Tyroglyphidae), order Acari, based on comparative morphological studies; historical, morphological, and general taxonomic studies. PMID- 21020475 TI - The expression and interaction of hereditary factors producing hypotrichosis in the mouse; histology and experimental results. PMID- 21020476 TI - An ecological study of the bighorn sheep in Rocky Mountain National Park, Colorado. PMID- 21020477 TI - Techniques for the study of the Norway rat. PMID- 21020479 TI - Anatomical terminology; the British point of view. PMID- 21020478 TI - No seasonal breeding cycle in dogs. PMID- 21020480 TI - Ontogenetic terms and the BNA. PMID- 21020481 TI - Terms of position and direction. PMID- 21020482 TI - Histological changes in adipose tissue of rats fed a vitamin E deficient diet high in cod liver oil. PMID- 21020483 TI - Epidermal nuclear size changes in methylcholanthrene induced carcinogenesis. PMID- 21020484 TI - The effects of exercise on the knee-joints of inbred mice. PMID- 21020485 TI - Cytological effects on tumors of a polysaccharide from S. marcescens culture filtrate. PMID- 21020486 TI - A cytochemical method for the localization and determination of protein in the presence of nucleic acid. PMID- 21020487 TI - Effects of various agents on the mating type substance of Paramecium aurelia variety 4. PMID- 21020488 TI - Sexual transformation of a genetically constituted female fish (Platypoecilus maculatus) into a functional male. PMID- 21020489 TI - Observations on pre- and postpubertal ovogenesis in the albino rat. PMID- 21020490 TI - Important aspects of biology in national and international economy. PMID- 21020491 TI - The effects of temperature on growth of Astasia, a colorless flagellate. PMID- 21020492 TI - Effect of temperature upon the growth of the ciliate Tetrahymena geleii under completely controlled conditions. PMID- 21020493 TI - The use of tantalum foil as a mechanical block for the separation of spinal cord and brain in chick embryos. PMID- 21020494 TI - The theory of competition within the body. PMID- 21020495 TI - The alteration of nerve cell differentiation in the grasshopper embryo by treatment with ultraviolet radiation. PMID- 21020496 TI - Migration of formative cells in regeneration of planarian pharynx. PMID- 21020497 TI - The development of the guinea pig ovary from sexual differentiation to maturity. PMID- 21020498 TI - Deutoplasmic substances in the egg of the golden hamster and their reduction during the pre-implantation stage of development. PMID- 21020499 TI - Response of sex glands and secondary sex characters of ZW and WW female axolotl larvae to testosterone propionate. PMID- 21020500 TI - Effect of thyroxin on mating frequency of domestic hens. PMID- 21020501 TI - Modifications in feather growth rate of thyroidectomized brown leghorn roosters following administration of thyroxin and estrogen. PMID- 21020502 TI - Effects of hypothyroidism on erythrocyte concentration in the domestic fowl. PMID- 21020503 TI - Observations on the mechanism of ovulation. PMID- 21020504 TI - The relation of temperature and the thyroid to mammalian reproductive physiology. PMID- 21020505 TI - Hormonal modification of sex development in female hamsters. PMID- 21020506 TI - The problem of delayed puberty in a monestrous wild mammal (Citellus tridecemlineatus). PMID- 21020507 TI - Phase boundary potentials as the origin of electrical phenomena in nerve. PMID- 21020508 TI - Orientation of chick nerve fibers by direct electric currents. PMID- 21020509 TI - Spontaneous 14-day rhythmic changes in the spiraling mechanism of leucocytes and amebas. PMID- 21020510 TI - The effect of various cations on action of KCl on fertilized Arbacia eggs. PMID- 21020511 TI - Karyokinetic lengthening and cleavage. PMID- 21020512 TI - A preliminary report on variations and their causes in weight, length, and diameter of chicken eggs. PMID- 21020513 TI - Effect of DDT on permeability to water in larval and adult Diptera. PMID- 21020514 TI - The adrenergic factor in reflex inhibition of the sphincter pupillae muscle. PMID- 21020515 TI - The kinetics of visual processes; dark adaptation. PMID- 21020516 TI - Influence of various gases contained in the colon on colon motility. PMID- 21020517 TI - The effect of renal trauma on the juxtaglomerular apparatus. PMID- 21020518 TI - Students brain-waves taken before and after classes. PMID- 21020519 TI - Studies in bird behavior. PMID- 21020520 TI - The cultivation of rickettsiae in the yolk-sac of developing chick embryos. PMID- 21020521 TI - Distribution of the nerves within the pancreas of the cat. PMID- 21020522 TI - Modifications in plumage pattern of thyroidectomized roosters following estrogen administration. PMID- 21020523 TI - Further study of the influence of translocations on the sex-determining mechanism in Sciara coprophila. PMID- 21020524 TI - Spermatogenesis in patroclinous Sciara males. PMID- 21020525 TI - The male gamete of Plasmodium. PMID- 21020526 TI - Effects of the injection of ascorbic acid on the Golgi elements of the frog adrenal. PMID- 21020527 TI - Effects of temperature on the Golgi elements of the frog tongue. PMID- 21020528 TI - The pyramidal tract; acid phosphatase in the axons of mammals. PMID- 21020529 TI - The development of the vascular pattern within the walls of the brain of the chick embryo. PMID- 21020530 TI - Cerebral regeneration induced by simultaneous intraocular grafting of newborn cerebral tissue and sciatic nerve in the mouse. PMID- 21020531 TI - The origin of the subcutaneous melanophores in the Silkie fowl. PMID- 21020532 TI - The reaction to female hormone of the breast-saddle chimaeric feathers in brown leghorn capons. PMID- 21020533 TI - Herkunftsgemass behavior in transplanted anuran tail blastemata. PMID- 21020534 TI - Nature of block to gastrulation in hybrid egg. PMID- 21020535 TI - Variability of the anestrous condition in the opossum, Didelphys virginiana. PMID- 21020536 TI - The inheritance of nuclear properties which find expression in the first 72 hours of development of Rana pipiens, Schreber. PMID- 21020537 TI - Monozygotic and dizygotic twin birth frequencies in the U.S. population. PMID- 21020538 TI - Endocrine activity of the tritocerebral commissure of Crago (Crustacea). PMID- 21020539 TI - Endocrine effects upon the claws of immature turtles, Pseudemys elegans. PMID- 21020540 TI - Plasma protein concentrations in adrenalectomized rats maintained on desoxycorticosterone acetate. PMID- 21020541 TI - Correlation between age at introitus and age at first litter in three strains of mice. PMID- 21020542 TI - The normal fallopian tube of the opossum and its reactions to estrogens, androgens and gonadotropins. PMID- 21020543 TI - Some alterations in the blood following the administration of diethylstilbestrol to normal and thyroidectomized rats and to rats given thiourea. PMID- 21020544 TI - Delayed ovulation in the macaque monkey. PMID- 21020545 TI - The morphology and histochemistry of the adrenal cortex after hypophysectomy. PMID- 21020546 TI - A possible difference determined by the sex alleles in haploid males of Habrobracon. PMID- 21020547 TI - Correlated defects in human agnathus. PMID- 21020548 TI - Type of regeneration in limbs of frogs after transplantation of adult skin. PMID- 21020549 TI - A study of the relationship between facet irregularities and eye color in lozenge alleles of Drosophila melanogaster. PMID- 21020550 TI - The effect of cobalt of the circulating blood and hemopoietic centers of the anuran larva. PMID- 21020552 TI - Periodic acceleration in frequency of brain-waves correlated with normal respiratory movements. PMID- 21020551 TI - Oxygen consumption and carbon dioxide elimination in Tetrahymena geleii Furgason. PMID- 21020554 TI - Studies on loci of action of DDT in the cockroach (Periplaneta americana). PMID- 21020553 TI - A somparison of the effect of water starvation on anoxic death at ordinary barometric pressures with anoxic death caused by barometric decompression. PMID- 21020555 TI - Influence of ingested glucose on the pain of exercising ischemic muscle. PMID- 21020556 TI - A comparison of stillbirth percentages among single and plural births in the total, the white and the colored U.S. populations. PMID- 21020557 TI - Sex-influence on growth-potential and female dominance in the coelenterate, Campanularia flexuosa. PMID- 21020558 TI - Developmental interactions of bithorax and growth rate genes in Drosophila melanogaster. PMID- 21020559 TI - The effect of posterior lobe principles and certain amines on the melanophores of Anolis carolinensis. PMID- 21020560 TI - Mapping of functioning sweat glands and estimation of sweat secretion by test papers. PMID- 21020561 TI - An improved medium for the culture of the flagellate Polytoma. PMID- 21020562 TI - The oxidative inactivation of poison ivy irritants and related phenolic derivatives by laccase. PMID- 21020563 TI - Comparison of the electrical activity of acetylcholine with other products of nerve metabolism. PMID- 21020564 TI - Observations on the developmental cycle of the lymphocystis virus in fish (Pleuronectes flesus, Stizostedion vitreum, Acerina cernua). PMID- 21020565 TI - Studies on filariasis; potential mosquito vectors of Wuchereria bancrofti. PMID- 21020566 TI - Trematoda as parasites of the Bufoninae (Amphibia). PMID- 21020567 TI - Micronucleate and amicronucleate races of Tillina magna. PMID- 21020569 TI - Unstable micronuclear behavior in an unusual race of Paramecium. PMID- 21020568 TI - The behavior of cytoplasmic structures in living conjugants of Paramecium bursaria. PMID- 21020570 TI - The use of antibodies in the purification of Trichomonas foetus (Protozoa) cultures. PMID- 21020571 TI - Further studies on the alteration of epithelial fat in the rat uterus during the estrous cycle, early pregnancy, and in the treated and untreated castrate. PMID- 21020572 TI - The course and incidence of the lateral costal branch of the internal mammary artery. PMID- 21020573 TI - Lymphocyte transformations in germinal centers (reaction centers) and in intestinal epithelium. PMID- 21020574 TI - The production of ovarian hormones during lactation in the mouse. PMID- 21020575 TI - Development of the aquaductus cochleae and the periotic (perilymphatic) duct. PMID- 21020576 TI - Analysis of variations of the bronchopulmonary segments in the left upper lobes of fifty lungs. PMID- 21020577 TI - Effect of temperature on potassium metabolism in chick embryo muscle. PMID- 21020578 TI - Exaggerated discharge of neurosomes from motor end plates into voluntary muscle. PMID- 21020579 TI - On the incidence of the foramen of Civinini and the porus crotaphiticobuccinatorius in American whites and Negroes. PMID- 21020580 TI - The electroencephalogram in concussion in cats. PMID- 21020581 TI - Gross structure of the subcutaneous layer in the anterior and lateral trunk of the male as shown by razor cuts. PMID- 21020582 TI - Growth in weight and stature in man; a study in kinetic anthropometry. PMID- 21020583 TI - Aspects of the mechanics of wrist joint action. PMID- 21020584 TI - The nerve supply of the anterior lobe of the armadillo hypophysis. PMID- 21020585 TI - A cytochemical study of the effects of KCN on alkaline phosphatase activity in the kidney and intestine. PMID- 21020587 TI - Studies on the nature and significance of Heinz-body formation in erythrocytes. PMID- 21020586 TI - Experiments on the fate of the transfused leukocyte. PMID- 21020588 TI - Osseous changes in estrogen-treated hypothyroid and low-protein-fed mice. PMID- 21020589 TI - Lateral pharyngeal derivatives associated with thyroid glands of inbred strains of mice. PMID- 21020590 TI - Hernias through the tunica albuginea testis. PMID- 21020591 TI - Centrifugal functional deterioration along the intramedullary portion of oxygen deprived motor nerve. PMID- 21020592 TI - Ovulatory cycle in the cervix of the monkey. PMID- 21020593 TI - Reduction of sympathetic ganglia in the trunk of the chick following removal of neural crest. PMID- 21020594 TI - Brain volume and volume of neocortex in mammals. PMID- 21020595 TI - On a human blastula recovered from the uterine cavity 4 days after ovulation. PMID- 21020597 TI - Differentiation of embryonic rat gonads transplanted to the adult omentum. PMID- 21020596 TI - Life sustaining adrenal cortical function of the mouse ovary. PMID- 21020598 TI - The ovaries in triploid axolotl females of different genotypes with respect to sex chromosomes. PMID- 21020599 TI - Further observations on the experimental production of ovarian cysts. PMID- 21020600 TI - A quantitative study of the hemopoietic organs of albino rats following intravenous injection of mustard and nitrogen mustards. PMID- 21020601 TI - A study of the development of the pharynx of the guinea pig with special emphasis on the origin and fate of the ultimobranchial body. PMID- 21020602 TI - Site and duration of humeral torsion in man. PMID- 21020603 TI - Fibers of the medullary center of the human cerebrum. PMID- 21020604 TI - The cerebellum of cyclostomes. PMID- 21020605 TI - A study of follicle-cell dispersion in ova by hyaluronidase. PMID- 21020606 TI - Hematology of blood spots in the chicken egg and its bearing on differential counts and macrophage development. PMID- 21020607 TI - The morphological basis for menstrual bleeding. PMID- 21020608 TI - Experimental production of scoliosis in rats. PMID- 21020609 TI - The effects of androgens, estrogens and equine gonadotropins on the mucin secreting cells and on glycogen in the reproductive tract of the female opossum. PMID- 21020610 TI - Glandular tissues of the adult mammalian ovary. PMID- 21020611 TI - Regeneration of human hairs in the eyebrows and in the scalp region superior to the ear. PMID- 21020612 TI - Alkaline phosphatase and acid phosphatase in the mast cell. PMID- 21020613 TI - Embryological stages in the development of spina bifida and myeloschisis. PMID- 21020614 TI - Reaction of the spinal cord to laminectomy. PMID- 21020615 TI - The influence of the peripheral field on the development of the mesencephalic V nucleus in Amblystoma. PMID- 21020616 TI - The effect of some barbiturates on tissues in vitro. PMID- 21020617 TI - The effect of continuous illumination on the ovaries of adrenalectomized rats. PMID- 21020618 TI - Hyperplasia in the kidney of the rat following unilateral nephrectomy. PMID- 21020619 TI - Fibrillar structure of adult human bone. PMID- 21020620 TI - The relationship between sex hormones and serum cholinesterase in the rat. PMID- 21020621 TI - The comparative value of supravital staining and dried smears in the study of blood and marrow cells. PMID- 21020622 TI - A mechanism for replacement pregnancy in a monestrous wild mammal (Citellus tridecemlineatus). PMID- 21020623 TI - Mitotic activity in regenerating corneal epithelium. PMID- 21020624 TI - A comparison of the tactile areas in the cerebellum of the cat and monkey (Macaca mulatta). PMID- 21020626 TI - Distribution of the axons from the motor cell groups of the spinal cord. PMID- 21020625 TI - Prolonged histories of vagus nerve regeneration patterns, sterile distal stumps, and sheath cell outgrowths. PMID- 21020627 TI - Changes in the mouse spleen following injection of an antiserum to mouse spleen and bone marrow (ACS). PMID- 21020628 TI - The nuclei of the human thalamus. PMID- 21020629 TI - Histological alterations in the nervous system of guinea pigs subjected to high amplitude percussion waves in water. PMID- 21020630 TI - Observations on secretion of urine by kidneys of fetal rats. PMID- 21020631 TI - The cultivation of chick embryo tissues in fully synthetic nutrients. PMID- 21020632 TI - Comparison of the response of urethral epithelia of male and female rats to the injection of estrogen. PMID- 21020633 TI - The major efferent connections of the basal ganglia. PMID- 21020634 TI - Induction of auditory vesicles from gill ectoderm in the salamander embryo. PMID- 21020635 TI - The development of the rattle in rattlesnakes. PMID- 21020636 TI - The histology of certain endocrine glands of adrenalin-injected male albino mice. PMID- 21020637 TI - Sudan Black B as an aid in studying leucocyte granules. PMID- 21020638 TI - Phases of the menstrual cycle in the macaque monkey. PMID- 21020639 TI - The arrangement of the segmental arteries in the left upper lobes of 50 lungs. PMID- 21020640 TI - Bilateral extra-articular ankylosis of the hip joints. PMID- 21020641 TI - The effect of low temperature immediately after explantation on thyroid cultures from chick embryos of 8 to 14 days incubation. PMID- 21020642 TI - Some effects of restricting the growth of nerves by ligature. PMID- 21020644 TI - Surface potentials and peripheral nerve injury. PMID- 21020643 TI - The production of pigment in white leghorn feathers and skin by melanophores derived from the neural crest of white Silkie bantam embryos. PMID- 21020645 TI - Spinal cord hypoplasia after limb amputation in the fetal rat. PMID- 21020646 TI - The pyramidal tract; the behavior of axonal acid phosphatase to maximal destruction of cells of origin in the monkey. PMID- 21020647 TI - Studies on the metrial gland in the mouse. PMID- 21020648 TI - Vitamin E deficiency in the monkey. PMID- 21020649 TI - Effects of mammalian thyroid powder on growth and maturation of thiourea-treated fishes. PMID- 21020650 TI - Subthalamo-tegmental tract. PMID- 21020651 TI - The congenitally single coronary artery; report of seven new cases, one with infarction of the right ventricular and atrial myocardium. PMID- 21020652 TI - The nervous pathways of chemical sense and taste in the fishes Prionotus and Trichogaster. PMID- 21020653 TI - Sympathetic infiltration of the cornea induced by the removal of the corneal epithelium. PMID- 21020654 TI - Neoplasia in aged rats following early vitamin A deficiency. PMID- 21020655 TI - Changes in the lipid content of adrenal glands with respect to sex, age and tumor incidence. PMID- 21020656 TI - A method for subjecting fetal rats to laparotomy and repeated subcutaneous injections. PMID- 21020657 TI - Anatomical factors involved in the blacking out phenomenon. PMID- 21020658 TI - [Not Available]. PMID- 21020659 TI - [Not Available]. PMID- 21020660 TI - [Not Available]. PMID- 21020662 TI - [Not Available]. PMID- 21020661 TI - [Not Available]. PMID- 21020663 TI - [Not Available]. PMID- 21020664 TI - [Not Available]. PMID- 21020665 TI - [Not Available]. PMID- 21020666 TI - [Not Available]. PMID- 21020667 TI - Research on Southeast Asia; problems and suggestions. PMID- 21020668 TI - Recent trends in American ethnology. PMID- 21020669 TI - Evolution in cultural anthropology; a reply to Leslie White. PMID- 21020670 TI - On the so-called anti-evolutionist fallacy; a reply to Leslie A. White. PMID- 21020671 TI - The skull of a Copper Eskimo. PMID- 21020672 TI - The action of sulfonamides on certain fungi pathogenic to man. PMID- 21020673 TI - Antigens and antibodies. PMID- 21020674 TI - Effect of caffeine and theophylline on striated muscle work curves. PMID- 21020675 TI - Haemocytometry with a camera. PMID- 21020676 TI - Deficiency in cortical function as a factor in the production of aeroneuroses. PMID- 21020677 TI - Studies on retarding agents for protozoa. PMID- 21020678 TI - A test for linkage of seven hereditary traits in the human. PMID- 21020679 TI - Notes on the incidence of three nematode parasites in the Manila area. PMID- 21020681 TI - [Not Available]. PMID- 21020680 TI - Field sampling for the estimation of wireworm populations. PMID- 21020682 TI - [Not Available]. PMID- 21020683 TI - [Not Available]. PMID- 21020684 TI - [Not Available]. PMID- 21020685 TI - [Not Available]. PMID- 21020686 TI - [Not Available]. PMID- 21020687 TI - [Not Available]. PMID- 21020688 TI - [Not Available]. PMID- 21020689 TI - [Not Available]. PMID- 21020690 TI - [Not Available]. PMID- 21020691 TI - [Not Available]. PMID- 21020692 TI - [Not Available]. PMID- 21020693 TI - [Not Available]. PMID- 21020694 TI - [Not Available]. PMID- 21020695 TI - [Not Available]. PMID- 21020696 TI - [Not Available]. PMID- 21020697 TI - [Not Available]. PMID- 21020698 TI - [Not Available]. PMID- 21020699 TI - [Not Available]. PMID- 21020700 TI - [Not Available]. PMID- 21020701 TI - [Not Available]. PMID- 21020702 TI - [Not Available]. PMID- 21020703 TI - [Not Available]. PMID- 21020704 TI - [Not Available]. PMID- 21020705 TI - [Not Available]. PMID- 21020706 TI - [Not Available]. PMID- 21020707 TI - [Not Available]. PMID- 21020708 TI - [Not Available]. PMID- 21020709 TI - [Not Available]. PMID- 21020710 TI - [Not Available]. PMID- 21020711 TI - [Not Available]. PMID- 21020712 TI - [Not Available]. PMID- 21020713 TI - [Not Available]. PMID- 21020714 TI - [Not Available]. PMID- 21020715 TI - [Not Available]. PMID- 21020716 TI - [Not Available]. PMID- 21020718 TI - [Not Available]. PMID- 21020717 TI - [Not Available]. PMID- 21020719 TI - [Not Available]. PMID- 21020720 TI - [Not Available]. PMID- 21020721 TI - [Not Available]. PMID- 21020722 TI - [Not Available]. PMID- 21020723 TI - [Not Available]. PMID- 21020724 TI - [Not Available]. PMID- 21020725 TI - [Not Available]. PMID- 21020726 TI - [Not Available]. PMID- 21020727 TI - [Not Available]. PMID- 21020728 TI - [Not Available]. PMID- 21020729 TI - [Not Available]. PMID- 21020730 TI - [Not Available]. PMID- 21020731 TI - [Not Available]. PMID- 21020732 TI - [Not Available]. PMID- 21020733 TI - [Not Available]. PMID- 21020734 TI - [Not Available]. PMID- 21020735 TI - [Not Available]. PMID- 21020736 TI - [Not Available]. PMID- 21020737 TI - Some ionic and osmotic equilibria of the erythrocyte. PMID- 21020738 TI - Dark adaptation. PMID- 21020739 TI - Reduction time of peripheral cutaneous blood as a means of evaluating fitness. PMID- 21020740 TI - Endocrine glands and gastric secretion. PMID- 21020741 TI - The striking inherent tonus of the deafferenated central pupilloconstrictor neurons. PMID- 21020742 TI - Blood studies in anaphylactic shock in dogs. PMID- 21020743 TI - The relation between tissue metabolism and physiological activity. PMID- 21020744 TI - Relationships between changes in muscle length, tone, tension, and pressure. PMID- 21020745 TI - The relationship between blood ketone levels and the storage of glycogen by the heart in acute experiments. PMID- 21020747 TI - Physiological standards. PMID- 21020746 TI - The electrosmotic transport of fluid through the walls of injured capillaries. PMID- 21020748 TI - The effect of benzedrine and other chemical agents upon the postconvulsive (electric shock) EEG. PMID- 21020749 TI - Method of assaying adrenal preparations for protective action against toxic material (typhoid vaccine). PMID- 21020750 TI - The effect of inhaled methyl disulphide on liver fat of rats. PMID- 21020751 TI - Analysis of lactic acid with a modification of the Conway microdiffusion unit. PMID- 21020752 TI - Determination of renal function in rats. PMID- 21020753 TI - The phosphatase activity of human spermatozoa. PMID- 21020754 TI - Height, weight and body index of school children; a correlation study. PMID- 21020755 TI - Brain, heart, thyroid, adrenals, and habitat. PMID- 21020756 TI - Studies on the cellular basis of regeneration in Nais paraguayensis, and the effects of x-rays thereon. PMID- 21020757 TI - Effects of the growth inhibitor, hexenolactone, on frog embryos; effects on diploid embryos; differential effects on haploid and diploid embryos. PMID- 21020758 TI - A comparison of regeneration rates and metamorphosis in Triturus and Amblystoma. PMID- 21020759 TI - Variations in the potency of thyrotrophic hormone of the pituitary in animals. PMID- 21020760 TI - The early evolution of fishes. PMID- 21020761 TI - [Not Available]. PMID- 21020762 TI - [Not Available]. PMID- 21020764 TI - [Not Available]. PMID- 21020763 TI - Experimental motion-sickness and attempts at therapy. PMID- 21020765 TI - [Not Available]. PMID- 21020766 TI - [Not Available]. PMID- 21020767 TI - [Not Available]. PMID- 21020768 TI - Investigations on the blood circulations of Gunder Hagg and Arne Anderson. PMID- 21020769 TI - [Not Available]. PMID- 21020770 TI - The electrocardiogram obtained directly from the human heart. PMID- 21020771 TI - [Not Available]. PMID- 21020772 TI - The Fischer cyanohydrin synthesis and the configurations of higher-carbon sugars and alcohols. PMID- 21020773 TI - The altrose group of substances. PMID- 21020774 TI - Carbohydrate orthoesters. PMID- 21020775 TI - Thio- and seleno-sugars. PMID- 21020776 TI - The carbohydrate components of the cardiac glycosides. PMID- 21020777 TI - Metabolism of the sugar alcohols and their derivatives. PMID- 21020779 TI - The fractionation of starch. PMID- 21020778 TI - The chemistry of the nucleic acids. PMID- 21020780 TI - Preparation and properties of starch esters. PMID- 21020781 TI - Cellulose esters of organic acids. PMID- 21020782 TI - A discussion of methods of value in research on plant polyuronides. PMID- 21020788 TI - Metabolism of acetoacetate in animal tissues. PMID- 21020795 TI - Studies on the metabolism of semen; general aspects; occurrence and distribution of cytochrome, certain enzymes and coenzymes. PMID- 21020796 TI - Studies on the metabolism of semen; glycolysis in spermatozoa. PMID- 21020801 TI - The colouring matters of galls. PMID- 21020798 TI - Phosphoric esters of the pancreas; choline glycerophosphate. PMID- 21020802 TI - Chromatography in aqueous solution with mineral precipitates insoluble in water; application to the separation of amino-acids by adsorption on Ag2S. PMID- 21020804 TI - The chemical estimation of vitamine E in vegetable oils. PMID- 21020807 TI - Faecal excretion of urobilinogen after fractures. PMID- 21020808 TI - The colorimetric estimation of synthetic oestrogens in pure solutions with special reference to the relative stabilities of stilboestrol and of dienoestrol. PMID- 21020810 TI - Desalting solutions of amino-acids. PMID- 21020809 TI - The isolation of a new sulphuric acid ester from the urine of pregnant mares. PMID- 21020811 TI - Changes in the chloride concentration of sweat with acclimatization. PMID- 21020812 TI - The chemical micro-biology of Kaffir beer. PMID- 21020813 TI - Determination of sulphur in biological material by hydrogenation. PMID- 21020814 TI - Differential adsorption of pepsin and rennin on foam. PMID- 21020815 TI - The permeability of cells. PMID- 21020816 TI - The physical chemistry of lipoid protein associations. PMID- 21020818 TI - The chemistry of cell nuclei. PMID- 21020817 TI - The structural proteins of the cell. PMID- 21020819 TI - Cytoplasmic ribonucleoproteins. PMID- 21020820 TI - The inorganic constituents of the cell. PMID- 21020821 TI - The detection of 3-hydroxysulphanilamide in the urine of patients treated with sulphanilamide. PMID- 21020822 TI - The metabolism of chrysene in the rat. PMID- 21020823 TI - The study of the fine structure of absorption spectra. PMID- 21020824 TI - The polarographic estimation of steroid hormones; the estimation of 17 ketosteroids in urinary extracts. PMID- 21020825 TI - The polarographic estimation of steroid hormones; polarography of related steroid hydrazones. PMID- 21020826 TI - [Not Available]. PMID- 21020827 TI - [Not Available]. PMID- 21020828 TI - [Not Available]. PMID- 21020829 TI - [Not Available]. PMID- 21020830 TI - [Not Available]. PMID- 21020831 TI - [Not Available]. PMID- 21020833 TI - [Not Available]. PMID- 21020832 TI - [Not Available]. PMID- 21020834 TI - [Not Available]. PMID- 21020835 TI - [Not Available]. PMID- 21020836 TI - [Not Available]. PMID- 21020837 TI - [Not Available]. PMID- 21020838 TI - [Not Available]. PMID- 21020839 TI - [Not Available]. PMID- 21020840 TI - [Not Available]. PMID- 21020841 TI - [Not Available]. PMID- 21020842 TI - [Not Available]. PMID- 21020843 TI - [Not Available]. PMID- 21020844 TI - [Not Available]. PMID- 21020845 TI - [Not Available]. PMID- 21020846 TI - [Not Available]. PMID- 21020847 TI - [Not Available]. PMID- 21020848 TI - [Not Available]. PMID- 21020849 TI - [Not Available]. PMID- 21020851 TI - [Not Available]. PMID- 21020852 TI - [Not Available]. PMID- 21020850 TI - [Not Available]. PMID- 21020853 TI - [Not Available]. PMID- 21020855 TI - [Not Available]. PMID- 21020854 TI - [Not Available]. PMID- 21020856 TI - [Not Available]. PMID- 21020858 TI - [Not Available]. PMID- 21020857 TI - [Not Available]. PMID- 21020859 TI - [Not Available]. PMID- 21020860 TI - [Not Available]. PMID- 21020861 TI - [Not Available]. PMID- 21020862 TI - The combination of fatty acids and related compounds with serum albumin; stabilization against heat denaturation. PMID- 21020863 TI - The combination of fatty acids and related compounds with serum albumin; stabilization against urea and guanidine denaturation. PMID- 21020864 TI - The effect of riboflavin deficiency upon carbohydrate metabolism in anoxia. PMID- 21020865 TI - Nicotinic acid values by chemical and microbiological methods; effect of hydrogen peroxide and infra-red rays on nicotinic acid. PMID- 21020866 TI - Pea starch, a starch of high amylose content. PMID- 21020867 TI - The presence of creatine in the testes of various invertebrates; the preparation of creatine phosphoric acid from fish testes. PMID- 21020868 TI - The effect of fat on the utilization of galactose by the albino rat. PMID- 21020869 TI - The effect of proteolytic enzymes on raw and heated casein. PMID- 21020870 TI - The influence of diet on the riboflavin metabolism of the rat. PMID- 21020871 TI - Radio-iodine and iodine fractionation studies of human goitrous thyroids. PMID- 21020872 TI - The effect of ribonucleic acid and its hydrolytic products and of desoxyribonucleic acid on succinic dehydrogenase and cytochrome oxidase. PMID- 21020873 TI - The biological conversion of l-serine to glycine. PMID- 21020874 TI - The metabolism of methylxanthines and their related methyluric acids. PMID- 21020875 TI - Micromethod for the determination of urea. PMID- 21020876 TI - The synthesis and properties of the acyl phosphates of some higher fatty acids. PMID- 21020877 TI - The effect of the dietary level of methionine on the rate of transmethylation reactions in vivo. PMID- 21020878 TI - The ultraviolet irradiation of quinine. PMID- 21020879 TI - Identification by distribution studies; isolation of antibiotic principles from Aspergillus ustus. PMID- 21020880 TI - The effect of certain experimental conditions on the formation of thyroxine from diiodotyrosine. PMID- 21020881 TI - Studies in carbohydrate metabolism; effects of hypo- and hyperinsulinism in rabbits. PMID- 21020882 TI - Some correlations of growth-promoting powers of proteins with their strepogenin content. PMID- 21020883 TI - The availability of vitamin B-6 in yeast to Saccharomyces carlsbergensis. PMID- 21020884 TI - Streptomycin; the chemical nature of streptidine. PMID- 21020885 TI - The separation of adenosinetriphosphatase from myosin and its activation by creatine. PMID- 21020886 TI - Kinetics of the deesterification of pectin. PMID- 21020887 TI - Improved methods of preparation of electropositive permselective protamine collodion membranes. PMID- 21020889 TI - [Not Available]. PMID- 21020888 TI - A theoretical analysis of the relative chemical effects of alpha particles and deuterons. PMID- 21020890 TI - [Not Available]. PMID- 21020891 TI - [Not Available]. PMID- 21020892 TI - [Not Available]. PMID- 21020893 TI - [Not Available]. PMID- 21020894 TI - [Not Available]. PMID- 21020895 TI - [Not Available]. PMID- 21020896 TI - [Not Available]. PMID- 21020897 TI - [Not Available]. PMID- 21020898 TI - A classification of jaw fractures with appropriate methods of immobilization. PMID- 21020900 TI - Penicillin in post-operative treatment. PMID- 21020899 TI - Cancer of the lip. PMID- 21020901 TI - Silicate cements. PMID- 21020902 TI - The use of acrylics in the replacement of anterior teeth. PMID- 21020903 TI - Dental education and research. PMID- 21020904 TI - The treatment of severe prognathism by Kostecka's operation. PMID- 21020905 TI - Further observations on penicillin-soluble albucid dressings. PMID- 21020906 TI - School dentistry in West Sussex. PMID- 21020907 TI - Silver amalgam stainless steel crowns; direct technique. PMID- 21020908 TI - The role of sulfa drugs in the control of oral infections. PMID- 21020909 TI - Cleft palate prosthesis for infants. PMID- 21020910 TI - Dental economics and office management. PMID- 21020911 TI - Conducting a successful practice with the aid of a business management program. PMID- 21020912 TI - Dentistry for children as an economic stabilizer for a general practice. PMID- 21020913 TI - The philosophy behind practice management teaching. PMID- 21020914 TI - The bungalow office has advantages for both patient and dentist. PMID- 21020915 TI - Social security and the dental profession; present and future benefits and their extension to self-employed persons. PMID- 21020916 TI - Dental care on a prepayment basis. PMID- 21020917 TI - A partpayment plan for dental service. PMID- 21020918 TI - The control center of practice management. PMID- 21020919 TI - SYSTEM is vital to building good practice, say dentists. PMID- 21020920 TI - DENTAL Service at Mayo General Hospital. PMID- 21020921 TI - Atomic energy. PMID- 21020922 TI - Drugs in treatment of periodontal disease. PMID- 21020923 TI - [Not Available]. PMID- 21020924 TI - [Not Available]. PMID- 21020925 TI - [Not Available]. PMID- 21020926 TI - [Not Available]. PMID- 21020927 TI - [Not Available]. PMID- 21020929 TI - The plastic artificial eye. PMID- 21020930 TI - Surgery about the oral cavity as related to muscle attachments. PMID- 21020928 TI - [Not Available]. PMID- 21020931 TI - The dental health problem in the United States. PMID- 21020933 TI - Cavity preparation for fixed bridge construction to date. PMID- 21020934 TI - Temporary protection of prepared bridge abutments. PMID- 21020932 TI - The diagnostic phase of fixed bridge construction. PMID- 21020935 TI - Pontic construction and assemblage. PMID- 21020936 TI - Cementation in fixed bridge construction. PMID- 21020937 TI - The periodontal aspect of fixed bridge diagnosis and construction. PMID- 21020938 TI - Trends and problems in fixed crown and bridge prosthesis. PMID- 21020939 TI - Diagnosis. PMID- 21020940 TI - Post-extraction complications. PMID- 21020941 TI - Occlusion and the Tweed concept in orthodontics. PMID- 21020943 TI - Sulphonamides and penicillin therapy as adjuncts in oral surgery. PMID- 21020942 TI - Occlusion; what it means to the prosthodontist. PMID- 21020944 TI - Necrosis and caries of the maxilliary bones. PMID- 21020945 TI - Chronic marginal gingivitis. PMID- 21020946 TI - Thumb and finger sucking. PMID- 21020947 TI - The goldfoil fillings. PMID- 21020948 TI - Public dental health. PMID- 21020949 TI - Occupational diseases among dentists. PMID- 21020950 TI - Prevention of oral diseases of occupational origin. PMID- 21020952 TI - A practical approach to exodontia problems. PMID- 21020951 TI - Elastic impressions for fixed bridges and partial dentures. PMID- 21020953 TI - The present status of dental caries research. PMID- 21020954 TI - Facial pain of known and unknown origin. PMID- 21020955 TI - [Not Available]. PMID- 21020956 TI - [Not Available]. PMID- 21020957 TI - [Not Available]. PMID- 21020958 TI - [Not Available]. PMID- 21020959 TI - [Not Available]. PMID- 21020960 TI - [Not Available]. PMID- 21020961 TI - [Not Available]. PMID- 21020962 TI - [Not Available]. PMID- 21020963 TI - [Not Available]. PMID- 21020964 TI - [Not Available]. PMID- 21020965 TI - [Not Available]. PMID- 21020966 TI - [Not Available]. PMID- 21020967 TI - [Not Available]. PMID- 21020968 TI - [Not Available]. PMID- 21020969 TI - [Not Available]. PMID- 21020970 TI - [Not Available]. PMID- 21020971 TI - [Not Available]. PMID- 21020972 TI - [Not Available]. PMID- 21020973 TI - Some aspects of dental conditions involving the nasal sinuses. PMID- 21020974 TI - ILLICIT practice; dental mechanic who took mouth impressions and supplied false teeth. PMID- 21020975 TI - [Not Available]. PMID- 21020976 TI - [Not Available]. PMID- 21020977 TI - [Not Available]. PMID- 21020978 TI - [Not Available]. PMID- 21020979 TI - [Not Available]. PMID- 21020980 TI - [Not Available]. PMID- 21020981 TI - [Not Available]. PMID- 21020982 TI - [Not Available]. PMID- 21020983 TI - [Not Available]. PMID- 21020984 TI - [Not Available]. PMID- 21020985 TI - [Not Available]. PMID- 21020986 TI - [Not Available]. PMID- 21020988 TI - [Not Available]. PMID- 21020987 TI - [Not Available]. PMID- 21020989 TI - [Not Available]. PMID- 21020990 TI - [Not Available]. PMID- 21020991 TI - [Not Available]. PMID- 21020992 TI - [Not Available]. PMID- 21020993 TI - [Not Available]. PMID- 21020994 TI - [Not Available]. PMID- 21020995 TI - [Not Available]. PMID- 21020996 TI - [Not Available]. PMID- 21020997 TI - [Not Available]. PMID- 21020998 TI - [Not Available]. PMID- 21020999 TI - [Not Available]. PMID- 21021001 TI - [Not Available]. PMID- 21021002 TI - [Not Available]. PMID- 21021000 TI - [Not Available]. PMID- 21021003 TI - [Not Available]. PMID- 21021004 TI - Problems of nutrition in Mexico. PMID- 21021005 TI - Nutritional status of economically poor families fed in a government-operated dining room in Mexico City. PMID- 21021006 TI - Activity as it affects the basal metabolism of college women. PMID- 21021007 TI - Variations in the basal metabolism of midwestern college women. PMID- 21021008 TI - Effect of guava juice and papaya on the acidity of the urine. PMID- 21021009 TI - The antirachitic value of winter and summer milk produced in Hawaii. PMID- 21021010 TI - Riboflavin and thiamin loss in cooking eggs. PMID- 21021011 TI - Composition and nutritive value of mushroom protein. PMID- 21021012 TI - The nutritive value of the protein in tobacco-seed oilmeal. PMID- 21021013 TI - The nutritive value of tobacco-seed oil. PMID- 21021015 TI - Studies on carotenoid metabolism; the relative provitamin A activity of carotene when introduced orally and parenterally in the rat. PMID- 21021014 TI - Mental response to added thiamine. PMID- 21021016 TI - Growth and food preference of rats fed a lactose-dried milk ration containing butter fat or corn oil. PMID- 21021017 TI - The influence of choline and of trypan blue upon the utilization of carotene and vitamin A for liver storage of Vitamin A. PMID- 21021018 TI - The nutritive value of canned foods; pyridoxine, biotin and folic acid. PMID- 21021019 TI - Nutritional status of rats on milk diets containing succinylsulfathiazole. PMID- 21021020 TI - Apparent prolongation of the life span of rats by intermittent fasting. PMID- 21021021 TI - The effect of different grades of cocoa upon the retention of dietary calcium by growing rats. PMID- 21021022 TI - The comparative value of niacin and nicotinamide. PMID- 21021023 TI - PRESENT knowledge of vitamin A in nutrition. PMID- 21021024 TI - PANTOTHENIC acid metabolism. PMID- 21021025 TI - BIOLOGIC activity of thienylalanine. PMID- 21021026 TI - THIAMINE deficiency, inanition, and anestrus. PMID- 21021027 TI - DENTAL caries in the cotton rat. PMID- 21021028 TI - HUMAN bioassay technic and applications. PMID- 21021029 TI - CECAL flora and nicotinic acid synthesis. PMID- 21021030 TI - ACTION of insulin. PMID- 21021033 TI - PANTOTHENIC acid, the adrenal cortex, and gray hair. PMID- 21021031 TI - THIOURACIL and liver cirrhosis. PMID- 21021032 TI - FAT and choline in the production of hemolytic anemia. PMID- 21021034 TI - USE of urinary vitamin excretion values in nutritional surveys. PMID- 21021035 TI - RICKETS and tooth development. PMID- 21021036 TI - NUTRITION in Army training camps. PMID- 21021037 TI - ANEMIA and granulocytopenia in relation to pantothenic acid and folic acid deficiencies. PMID- 21021038 TI - SOLUBILITY and biologic acitivity of riboflavin derivatives. PMID- 21021040 TI - [Not Available]. PMID- 21021039 TI - [Not Available]. PMID- 21021041 TI - [Not Available]. PMID- 21021042 TI - EUGENICS in England. PMID- 21021043 TI - Sexual plants with high chromosome number from an individual plant selection in a natural population of guayule and mariola. PMID- 21021044 TI - Genetics of natural populations; experimental reproduction of some of the changes caused by natural selection in certain populations of Drosophila pseudoobscura. PMID- 21021046 TI - The mechanism of non-random segregation of sex chromosomes in male Drosophila miranda. PMID- 21021045 TI - An analysis of translocations in the mouse. PMID- 21021047 TI - Mosaic dominance in the inheritance of color patterns in the lady-bird beetle, Harmonia axyridis. PMID- 21021048 TI - Greying induced by x-rays in the mouse. PMID- 21021049 TI - The effect of delaying time of development on mutation rate. PMID- 21021050 TI - Gene action and histological specificity of pigmentation patterns of certain R alleles. PMID- 21021051 TI - Breeding experiments with the invariably female, strictly matroclinous fish, Mollienisia formosa. PMID- 21021052 TI - Inheritance of susceptibility to dental caries in rats (Mus norwegicus). PMID- 21021053 TI - Analysis of the sex-linked mutation rate in the Florida high stock. PMID- 21021054 TI - Intracellular alkaline phosphatase activity. PMID- 21021055 TI - Failure of sperm of Habrobracon diploid males to penetrate the eggs. PMID- 21021056 TI - Physiological effects on spontaneous mutation rate in Drosophila. PMID- 21021057 TI - Constitution of liver and spleen as a physical basis for genetic resistance to mouse typhoid. PMID- 21021058 TI - Erythrocyte mosaics among bovine twins and quadruplets. PMID- 21021059 TI - Ovarian transplantation as a tool in genetic research. PMID- 21021060 TI - Isochromosomes and telocentrics in Triticum vulgare. PMID- 21021061 TI - Extent of genetic differences in male genitalia between Hippodamia quinquesignata and H. convergens (lady beetles). PMID- 21021062 TI - The inheritance of spaced teeth. PMID- 21021063 TI - An analysis of male development in Melandrium by means of Y chromosome deficiencies. PMID- 21021064 TI - A case of inherited resistance to radiation in bacteria. PMID- 21021066 TI - [Not Available]. PMID- 21021065 TI - Cytogenetic studies in Solanum, sect. Tuberarium. PMID- 21021067 TI - Interspecific hybridization within the genus Betula. PMID- 21021068 TI - Cytological studies in Triton. PMID- 21021069 TI - Meiosis in Anemone apennina with special reference to chiasma localisation. PMID- 21021071 TI - The shape of the spindle at metaphase is conditioned by the shape of its molecules. PMID- 21021070 TI - Small samples of a Poisson series. PMID- 21021072 TI - Cytological studies on Dipnoi, Urodela, Anura, and Emys. PMID- 21021075 TI - Hybrid vigour in crosses between pure lines of Galeopsis tetrahit. PMID- 21021073 TI - [Not Available]. PMID- 21021074 TI - The theory of evolution from a biochemical point of view. PMID- 21021076 TI - A haploid sugar beet after colchicine treatment. PMID- 21021077 TI - The triploid progeny of the cross diploid x tetraploid Populus tremula. PMID- 21021078 TI - Inheritance of pneumatisation of the mastoid bone. PMID- 21021080 TI - A crossing-over decrease caused by a new sex-linked lethal. PMID- 21021079 TI - Cytological studies of extra fragment chromosomes in rye; transmission and multiplication of standard fragments and iso-fragments. PMID- 21021081 TI - Ascorbic acid in Rosa hybrids. PMID- 21021082 TI - Equilibrium of trivalents and the mechanism of chromosome movements. PMID- 21021083 TI - Equilibrium of trivalents at metaphase. PMID- 21021084 TI - Chromosome numbers of the progeny from the cross triploid x tetraploid Populus tremula. PMID- 21021085 TI - [Not Available]. PMID- 21021086 TI - The temperature effect on pollen formation and meiosis in Hieracium robustum. PMID- 21021087 TI - Morphology and chemistry of the metaphase spindle. PMID- 21021089 TI - [Not Available]. PMID- 21021088 TI - Inheritance of wing dimorphism in Pterostichus anthracinus Ill. PMID- 21021090 TI - Structural changes of the Y chromosome in the offspring of polyploid Melandrium. PMID- 21021091 TI - Abortive egg cells in the mouse. PMID- 21021092 TI - Cytological studies of extra fragment chromosomes in rye; the mechanism of non disjunction at the pollen mitosis. PMID- 21021094 TI - Notes on the colchicine-meiosis of Allium cernuum. PMID- 21021093 TI - Drastic morphological mutations in barley. PMID- 21021095 TI - A rapid method for sorting polyploid material. PMID- 21021096 TI - Marriage and children for epileptics. PMID- 21021097 TI - The existence of an optimum interval between births. PMID- 21021098 TI - WHAT constitutes obscene literature? PMID- 21021099 TI - Marriage of coeds to fellow-students. PMID- 21021100 TI - Changing sex patterns and the war. PMID- 21021101 TI - Teaching college marriage courses; a symposium. PMID- 21021102 TI - Preparation of marriage; a part of effective living. PMID- 21021103 TI - Trends in teaching family relations. PMID- 21021104 TI - Marriage education in a junior college. PMID- 21021105 TI - Highlights of a marriage course. PMID- 21021106 TI - Courses in marriage and family relations. PMID- 21021107 TI - Youth and marriage today. PMID- 21021108 TI - Course in psychology of marriage and family relations for American soldiers. PMID- 21021109 TI - [Not Available]. PMID- 21021110 TI - [Not Available]. PMID- 21021111 TI - [Not Available]. PMID- 21021112 TI - [Not Available]. PMID- 21021114 TI - [Not Available]. PMID- 21021115 TI - [Not Available]. PMID- 21021113 TI - [Not Available]. PMID- 21021118 TI - The film in education. PMID- 21021116 TI - Food and maternal morbidity and mortality. PMID- 21021117 TI - Housing in Sweden. PMID- 21021119 TI - [Not Available]. PMID- 21021121 TI - [Not Available]. PMID- 21021120 TI - [Not Available]. PMID- 21021122 TI - [Not Available]. PMID- 21021123 TI - [Not Available]. PMID- 21021124 TI - [Not Available]. PMID- 21021126 TI - [Not Available]. PMID- 21021125 TI - [Not Available]. PMID- 21021127 TI - [Not Available]. PMID- 21021128 TI - [Not Available]. PMID- 21021129 TI - [Not Available]. PMID- 21021130 TI - [Not Available]. PMID- 21021131 TI - [Not Available]. PMID- 21021132 TI - [Not Available]. PMID- 21021133 TI - [Not Available]. PMID- 21021135 TI - Ur of the Chaldees and the influence of Abraham on the history of medicine. PMID- 21021134 TI - [Not Available]. PMID- 21021136 TI - American sectarian medical colleges before the Civil War. PMID- 21021137 TI - Leaves from a bibliotheca obstetrica. PMID- 21021138 TI - The Miller collection in the Library of the Richmond Academy of Medicine. PMID- 21021139 TI - Liver therapy advocated during the last century for the anemias. PMID- 21021140 TI - New concepts in gout. PMID- 21021141 TI - Some thoughts on the feeding and homoeopathic therapeutics of fat dyspepsia in infants. PMID- 21021143 TI - How can we best promote homeopathy in the United States? PMID- 21021142 TI - Homoeopathic therapy in some nerve diseases; neurasthenia. PMID- 21021144 TI - Selenium. PMID- 21021145 TI - A review of the status of homeopathic education in the United States of America. PMID- 21021146 TI - Some fragmentary reminiscences of the early history of homeopathy in Michigan. PMID- 21021147 TI - Age as a factor in certain obstetrical conditions. PMID- 21021148 TI - Abruptio placentae. PMID- 21021151 TI - Diagnosis of diseases of the fundus. PMID- 21021150 TI - A case report on ligation of the common femoral vein in phlebothrombosis. PMID- 21021149 TI - Hypertrophic rhinitis. PMID- 21021152 TI - Wartime ear injuries. PMID- 21021153 TI - Hysterical paralysis in the lower extremities. PMID- 21021154 TI - Hospitals of yesteryear. PMID- 21021155 TI - Significant changes in the British hospital system. PMID- 21021156 TI - Three Gras in the developing relationship of medical education and care. PMID- 21021157 TI - Congress studies plan to broaden coverage under Social Security. PMID- 21021158 TI - Neonatal crying; a study of its incidence, causes and control. PMID- 21021159 TI - Personnel organization no substitute for good personnel relations. PMID- 21021160 TI - DEVELOPING a rural community hospital. PMID- 21021161 TI - The Hospital Survey and Construction Act (S.-191). PMID- 21021162 TI - Personnel policies and conditions of service; the personnel of the nursing department of the Catholic hospital. PMID- 21021163 TI - The emphasis is on pre in fabrication of buildings. PMID- 21021164 TI - New venture in nurse education. PMID- 21021165 TI - Massillon Hospital presents the nicest nurses' home per cubic foot. PMID- 21021166 TI - Education while they wait. PMID- 21021167 TI - The library comes to the patient. PMID- 21021168 TI - Who will help the chronically ill. PMID- 21021169 TI - You may be held liable for unauthorized disclosure of patients' medical records. PMID- 21021170 TI - Color scheme for the comfort of the convalescent. PMID- 21021172 TI - The pattern for complete service. PMID- 21021171 TI - Action now toward better rural health. PMID- 21021173 TI - [Not Available]. PMID- 21021174 TI - [Not Available]. PMID- 21021175 TI - [Not Available]. PMID- 21021176 TI - [Not Available]. PMID- 21021177 TI - [Not Available]. PMID- 21021178 TI - [Not Available]. PMID- 21021179 TI - [Not Available]. PMID- 21021180 TI - [Not Available]. PMID- 21021181 TI - [Not Available]. PMID- 21021182 TI - [Not Available]. PMID- 21021183 TI - [Not Available]. PMID- 21021184 TI - [Not Available]. PMID- 21021185 TI - [Not Available]. PMID- 21021186 TI - [Not Available]. PMID- 21021187 TI - [Not Available]. PMID- 21021188 TI - [Not Available]. PMID- 21021190 TI - [Not Available]. PMID- 21021189 TI - [Not Available]. PMID- 21021191 TI - [Not Available]. PMID- 21021192 TI - [Not Available]. PMID- 21021193 TI - [Not Available]. PMID- 21021194 TI - [Not Available]. PMID- 21021195 TI - [Not Available]. PMID- 21021196 TI - [Not Available]. PMID- 21021197 TI - [Not Available]. PMID- 21021198 TI - [Not Available]. PMID- 21021199 TI - [Not Available]. PMID- 21021200 TI - [Not Available]. PMID- 21021201 TI - [Not Available]. PMID- 21021202 TI - [Not Available]. PMID- 21021203 TI - [Not Available]. PMID- 21021204 TI - [Not Available]. PMID- 21021205 TI - Industrial psychiatry in the community of Oak Ridge. PMID- 21021206 TI - Plumbophobia; occupational lead poisoning. PMID- 21021207 TI - The organization of a mental hygiene unit in industry. PMID- 21021208 TI - Edrisal in the treatment of dysmenorrhea. PMID- 21021209 TI - DOCTOR in industry. PMID- 21021210 TI - General considerations for sanitation and public health in tropical industry. PMID- 21021211 TI - Some thoughts after 30 years in industry. PMID- 21021212 TI - The epileptic; who he is; what he can be. PMID- 21021214 TI - The severely disabled. PMID- 21021213 TI - Labor and rehabilitation. PMID- 21021215 TI - A new trend in occupational therapy. PMID- 21021216 TI - Prevention of blindness and vocational rehabilitation. PMID- 21021217 TI - Vocational rehabilitation with limited personnel. PMID- 21021218 TI - Vermont's program for psychoneurotics. PMID- 21021219 TI - Vocational rehabilitation for the cerebral palsied. PMID- 21021220 TI - Some anomalies of feeble-mindedness. PMID- 21021222 TI - Proper placement as therapy in emotional handicaps. PMID- 21021221 TI - The hard of hearing. PMID- 21021223 TI - RUDIMENTS of rehabilitation. PMID- 21021224 TI - Tuberculosis rehabilitation center. PMID- 21021225 TI - [Not Available]. PMID- 21021227 TI - [Not Available]. PMID- 21021226 TI - [Not Available]. PMID- 21021228 TI - [Not Available]. PMID- 21021229 TI - [Not Available]. PMID- 21021230 TI - [Not Available]. PMID- 21021231 TI - [Not Available]. PMID- 21021232 TI - [Not Available]. PMID- 21021233 TI - [Not Available]. PMID- 21021234 TI - [Not Available]. PMID- 21021235 TI - [Not Available]. PMID- 21021237 TI - [Not Available]. 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PMID- 21021265 TI - [Not Available]. PMID- 21021264 TI - [Not Available]. PMID- 21021266 TI - [Not Available]. PMID- 21021267 TI - [Not Available]. PMID- 21021268 TI - [Not Available]. PMID- 21021269 TI - [Not Available]. PMID- 21021270 TI - [Not Available]. PMID- 21021271 TI - [Not Available]. PMID- 21021272 TI - [Not Available]. PMID- 21021273 TI - [Not Available]. PMID- 21021274 TI - [Not Available]. PMID- 21021276 TI - [Not Available]. PMID- 21021275 TI - [Not Available]. PMID- 21021277 TI - [Not Available]. PMID- 21021278 TI - [Not Available]. PMID- 21021279 TI - [Not Available]. PMID- 21021280 TI - [Not Available]. PMID- 21021281 TI - [Not Available]. PMID- 21021282 TI - [Not Available]. PMID- 21021283 TI - [Not Available]. PMID- 21021284 TI - Bilateral hydronephrosis in horseshoe kidney. PMID- 21021285 TI - Subacute bacterial endocarditis; report of enterococcal infection treated with penicillin. PMID- 21021286 TI - Pulmonary embolism and venous thrombosis. PMID- 21021287 TI - Pheochromocytoma; a case history and a review of literature. PMID- 21021288 TI - The goitrogenic and toxic effects upon the albino rat of three pyrimidine containing compounds chemically related to thiouracil. PMID- 21021289 TI - The development of anesthesia. PMID- 21021290 TI - [Not Available]. PMID- 21021291 TI - [Not Available]. PMID- 21021292 TI - [Not Available]. PMID- 21021294 TI - [Not Available]. PMID- 21021293 TI - [Not Available]. PMID- 21021295 TI - [Not Available]. PMID- 21021296 TI - [Not Available]. PMID- 21021297 TI - [Not Available]. PMID- 21021298 TI - [Not Available]. PMID- 21021300 TI - [Not Available]. PMID- 21021299 TI - [Not Available]. PMID- 21021301 TI - [Not Available]. PMID- 21021302 TI - [Not Available]. PMID- 21021303 TI - [Not Available]. PMID- 21021304 TI - [Not Available]. PMID- 21021305 TI - [Not Available]. PMID- 21021306 TI - [Not Available]. PMID- 21021307 TI - [Not Available]. PMID- 21021308 TI - [Not Available]. PMID- 21021309 TI - [Not Available]. PMID- 21021310 TI - [Not Available]. PMID- 21021311 TI - [Not Available]. PMID- 21021312 TI - [Not Available]. PMID- 21021313 TI - [Not Available]. PMID- 21021314 TI - [Not Available]. PMID- 21021316 TI - [Not Available]. PMID- 21021315 TI - [Not Available]. PMID- 21021317 TI - [Not Available]. PMID- 21021318 TI - [Not Available]. PMID- 21021319 TI - [Not Available]. PMID- 21021320 TI - [Not Available]. PMID- 21021321 TI - [Not Available]. PMID- 21021322 TI - [Not Available]. PMID- 21021323 TI - [Not Available]. PMID- 21021324 TI - [Not Available]. PMID- 21021325 TI - [Not Available]. PMID- 21021326 TI - [Not Available]. PMID- 21021327 TI - [Not Available]. PMID- 21021328 TI - [Not Available]. PMID- 21021329 TI - [Not Available]. PMID- 21021330 TI - [Not Available]. PMID- 21021331 TI - [Not Available]. PMID- 21021332 TI - [Not Available]. PMID- 21021333 TI - [Not Available]. PMID- 21021334 TI - [Not Available]. PMID- 21021335 TI - [Not Available]. 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PMID- 21021363 TI - [Not Available]. PMID- 21021364 TI - [Not Available]. PMID- 21021365 TI - [Not Available]. PMID- 21021367 TI - [Not Available]. PMID- 21021366 TI - [Not Available]. PMID- 21021368 TI - [Not Available]. PMID- 21021369 TI - [Not Available]. PMID- 21021370 TI - [Not Available]. PMID- 21021371 TI - [Not Available]. PMID- 21021372 TI - [Not Available]. PMID- 21021373 TI - [Not Available]. PMID- 21021374 TI - [Not Available]. PMID- 21021375 TI - [Not Available]. PMID- 21021376 TI - [Not Available]. PMID- 21021377 TI - [Not Available]. PMID- 21021378 TI - [Not Available]. PMID- 21021379 TI - [Not Available]. PMID- 21021380 TI - [Not Available]. PMID- 21021381 TI - [Not Available]. PMID- 21021382 TI - [Not Available]. PMID- 21021383 TI - [Not Available]. PMID- 21021384 TI - [Not Available]. PMID- 21021385 TI - [Not Available]. PMID- 21021386 TI - [Not Available]. PMID- 21021387 TI - [Not Available]. PMID- 21021388 TI - [Not Available]. PMID- 21021389 TI - [Not Available]. PMID- 21021391 TI - [Not Available]. PMID- 21021390 TI - [Not Available]. PMID- 21021392 TI - [Not Available]. PMID- 21021393 TI - [Not Available]. PMID- 21021394 TI - [Not Available]. PMID- 21021395 TI - [Not Available]. PMID- 21021396 TI - [Not Available]. PMID- 21021398 TI - [Not Available]. PMID- 21021397 TI - [Not Available]. PMID- 21021399 TI - [Not Available]. PMID- 21021400 TI - [Not Available]. PMID- 21021401 TI - [Not Available]. PMID- 21021402 TI - [Not Available]. PMID- 21021403 TI - [Not Available]. PMID- 21021404 TI - [Not Available]. PMID- 21021405 TI - [Not Available]. PMID- 21021406 TI - [Not Available]. PMID- 21021407 TI - [Not Available]. PMID- 21021408 TI - [Not Available]. PMID- 21021409 TI - [Not Available]. PMID- 21021410 TI - [Not Available]. PMID- 21021411 TI - [Not Available]. PMID- 21021412 TI - [Not Available]. PMID- 21021413 TI - [Not Available]. PMID- 21021415 TI - [Not Available]. PMID- 21021414 TI - [Not Available]. PMID- 21021416 TI - [Not Available]. PMID- 21021417 TI - [Not Available]. PMID- 21021418 TI - [Not Available]. PMID- 21021419 TI - [Not Available]. PMID- 21021420 TI - [Not Available]. PMID- 21021421 TI - [Not Available]. PMID- 21021422 TI - [Not Available]. PMID- 21021423 TI - [Not Available]. PMID- 21021425 TI - [Not Available]. PMID- 21021424 TI - [Not Available]. PMID- 21021426 TI - [Not Available]. PMID- 21021427 TI - [Not Available]. PMID- 21021428 TI - [Not Available]. PMID- 21021429 TI - [Not Available]. PMID- 21021430 TI - [Not Available]. PMID- 21021431 TI - [Not Available]. PMID- 21021432 TI - [Not Available]. PMID- 21021433 TI - [Not Available]. PMID- 21021434 TI - [Not Available]. PMID- 21021435 TI - [Not Available]. PMID- 21021436 TI - [Not Available]. PMID- 21021438 TI - [Not Available]. PMID- 21021437 TI - [Not Available]. PMID- 21021440 TI - [Not Available]. PMID- 21021439 TI - [Not Available]. PMID- 21021441 TI - [Not Available]. PMID- 21021442 TI - [Not Available]. PMID- 21021443 TI - [Not Available]. PMID- 21021444 TI - [Not Available]. PMID- 21021445 TI - [Not Available]. PMID- 21021446 TI - [Not Available]. PMID- 21021447 TI - [Not Available]. PMID- 21021448 TI - [Not Available]. PMID- 21021449 TI - [Not Available]. PMID- 21021450 TI - [Not Available]. PMID- 21021451 TI - [Not Available]. PMID- 21021453 TI - [Not Available]. PMID- 21021452 TI - [Not Available]. PMID- 21021454 TI - [Not Available]. PMID- 21021456 TI - [Not Available]. PMID- 21021455 TI - [Not Available]. PMID- 21021457 TI - [Not Available]. PMID- 21021458 TI - [Not Available]. PMID- 21021459 TI - [Not Available]. PMID- 21021460 TI - [Not Available]. PMID- 21021462 TI - Rheumatic heart. PMID- 21021461 TI - [Not Available]. PMID- 21021463 TI - The influence of new moon and full moon on malarial fever. PMID- 21021464 TI - Palsy of left arm after anesthesia treated by vitamin B. PMID- 21021465 TI - The role of the skin in health and disease. PMID- 21021466 TI - An observation on the psychology of persons attending the out-patients department of a general hospital. PMID- 21021467 TI - Sulpha drugs and their various uses. PMID- 21021468 TI - Chillblain. PMID- 21021469 TI - How to treat pulmonary tuberculosis case running concurrently with malaria. PMID- 21021470 TI - Psychology of marriage. PMID- 21021472 TI - ARTIFICIAL respiration. PMID- 21021471 TI - Sex glands in therapy. PMID- 21021473 TI - [Not Available]. PMID- 21021474 TI - [Not Available]. PMID- 21021475 TI - [Not Available]. PMID- 21021476 TI - [Not Available]. PMID- 21021477 TI - [Not Available]. PMID- 21021478 TI - [Not Available]. PMID- 21021479 TI - [Not Available]. PMID- 21021480 TI - [Not Available]. PMID- 21021481 TI - [Not Available]. PMID- 21021482 TI - [Not Available]. PMID- 21021483 TI - [Not Available]. PMID- 21021485 TI - [Not Available]. PMID- 21021484 TI - [Not Available]. PMID- 21021486 TI - Surgery of the patent ductus arteriosus. PMID- 21021487 TI - An account of the medical services of the National Liberation Army of Jugoslavia and of the R.A.M.C. assistance given to it. PMID- 21021488 TI - A comparative study of the protozoan parasites of man. PMID- 21021489 TI - [Not Available]. PMID- 21021490 TI - [Not Available]. PMID- 21021491 TI - [Not Available]. PMID- 21021492 TI - [Not Available]. PMID- 21021493 TI - [Not Available]. PMID- 21021494 TI - [Not Available]. PMID- 21021495 TI - [Not Available]. PMID- 21021496 TI - [Not Available]. PMID- 21021497 TI - [Not Available]. PMID- 21021498 TI - [Not Available]. PMID- 21021499 TI - [Not Available]. PMID- 21021500 TI - [Not Available]. PMID- 21021501 TI - [Not Available]. PMID- 21021502 TI - Ectopic gestation. PMID- 21021503 TI - A brief survey of the progress of diagnostic radiology from the time of Prof. Roentgen's discovery of x-rays. PMID- 21021504 TI - A case of eclampsia treated with vitamin B1 in massive doses. PMID- 21021505 TI - [Not Available]. PMID- 21021506 TI - [Not Available]. PMID- 21021507 TI - [Not Available]. PMID- 21021508 TI - [Not Available]. PMID- 21021509 TI - [Not Available]. PMID- 21021510 TI - [Not Available]. PMID- 21021511 TI - [Not Available]. PMID- 21021512 TI - [Not Available]. PMID- 21021513 TI - [Not Available]. PMID- 21021514 TI - [Not Available]. PMID- 21021515 TI - [Not Available]. PMID- 21021516 TI - [Not Available]. PMID- 21021517 TI - [Not Available]. PMID- 21021518 TI - [Not Available]. PMID- 21021520 TI - [Not Available]. PMID- 21021519 TI - [Not Available]. PMID- 21021521 TI - [Not Available]. PMID- 21021522 TI - [Not Available]. PMID- 21021524 TI - [Not Available]. PMID- 21021523 TI - [Not Available]. PMID- 21021525 TI - [Not Available]. PMID- 21021526 TI - [Not Available]. PMID- 21021527 TI - [Not Available]. PMID- 21021528 TI - [Not Available]. PMID- 21021529 TI - [Not Available]. PMID- 21021530 TI - [Not Available]. PMID- 21021531 TI - [Not Available]. PMID- 21021533 TI - [Not Available]. PMID- 21021532 TI - [Not Available]. PMID- 21021534 TI - [Not Available]. PMID- 21021535 TI - [Not Available]. PMID- 21021536 TI - [Not Available]. PMID- 21021537 TI - [Not Available]. PMID- 21021538 TI - [Not Available]. PMID- 21021539 TI - [Not Available]. PMID- 21021540 TI - [Not Available]. PMID- 21021541 TI - [Not Available]. PMID- 21021542 TI - [Not Available]. PMID- 21021543 TI - [Not Available]. PMID- 21021544 TI - [Not Available]. PMID- 21021545 TI - [Not Available]. PMID- 21021547 TI - [Not Available]. PMID- 21021546 TI - [Not Available]. PMID- 21021548 TI - [Not Available]. PMID- 21021549 TI - [Not Available]. PMID- 21021550 TI - [Not Available]. PMID- 21021551 TI - [Not Available]. PMID- 21021552 TI - [Not Available]. PMID- 21021553 TI - [Not Available]. PMID- 21021554 TI - [Not Available]. PMID- 21021555 TI - [Not Available]. PMID- 21021556 TI - [Not Available]. PMID- 21021557 TI - [Not Available]. PMID- 21021558 TI - [Not Available]. PMID- 21021559 TI - [Not Available]. PMID- 21021560 TI - [Not Available]. PMID- 21021561 TI - [Not Available]. PMID- 21021563 TI - [Not Available]. PMID- 21021562 TI - [Not Available]. PMID- 21021564 TI - [Not Available]. PMID- 21021565 TI - [Not Available]. PMID- 21021566 TI - [Not Available]. PMID- 21021567 TI - [Not Available]. PMID- 21021568 TI - [Not Available]. PMID- 21021569 TI - [Not Available]. PMID- 21021570 TI - [Not Available]. PMID- 21021571 TI - [Not Available]. PMID- 21021572 TI - [Not Available]. PMID- 21021573 TI - [Not Available]. PMID- 21021574 TI - [Not Available]. PMID- 21021575 TI - [Not Available]. PMID- 21021576 TI - [Not Available]. PMID- 21021577 TI - [Not Available]. PMID- 21021578 TI - [Not Available]. PMID- 21021579 TI - [Not Available]. PMID- 21021580 TI - [Not Available]. PMID- 21021581 TI - [Not Available]. PMID- 21021582 TI - [Not Available]. PMID- 21021583 TI - [Not Available]. PMID- 21021584 TI - [Not Available]. PMID- 21021585 TI - A clinical method of determining the specific renal functions of glomerular filtration, maximal tubular excretion or reabsorption (and effective blood flow) using a single injection of a single substance. PMID- 21021586 TI - A comparative study of mercuhydrin and mercupurin, oral and parenteral. PMID- 21021587 TI - The effect of theophylline aminoisobutanol in the failing experimental heart. PMID- 21021588 TI - Effect of stimuli originating in the upper abdomen in the causation of reflex shortening of the esophagus. PMID- 21021589 TI - Gastrocolic fistula; an experimental study. PMID- 21021590 TI - The detection of dangerous carriers of hemolytic streptococci by the measurement of their streptococcal output. PMID- 21021591 TI - Antipneumococcus hyaluronidase activity in human serum. PMID- 21021592 TI - The effect of superimposed bacterial pneumonia on the severity of sublethal infection with influenza virus. PMID- 21021593 TI - The significance of the accessory spleen. PMID- 21021594 TI - Observations on the effect of massive doses of iron given intravenously to patients with hypochromic anemia. PMID- 21021595 TI - The action of various drugs on the prothrombin of the blood. PMID- 21021596 TI - The effect of thiouracil on leukemia with a clinicopathologic report of a case of chronic myeloid leukemia that developed an extreme neutropenic leukopenia. PMID- 21021597 TI - Reactions from universal donor blood. PMID- 21021598 TI - The syndrome of hyperventilation. PMID- 21021599 TI - Phospholipids of liver and blood studied with radioactive phosphorus. PMID- 21021600 TI - Sequelae of trench foot and their treatment by lumbar sympathectomy. PMID- 21021601 TI - Toxic manifestations following large doses of ertron. PMID- 21021602 TI - The effect of infection and trauma on the excretion of urinary cortin. PMID- 21021603 TI - The clinical significance of the functional behavior of adenomas of the thyroid gland. PMID- 21021604 TI - Penicillin and dicumarol, and penicillin in the treatment of subacute bacterial endocarditis. PMID- 21021605 TI - A study of beriberi heart disease at the Cincinnati General Hospital. PMID- 21021606 TI - Follow-up studies of patients with cardiac wounds. PMID- 21021607 TI - The precordial electrocardiogram in high lateral myocardial infarction. PMID- 21021608 TI - Electrocardiographic diagnosis of right ventricular lesions with especial reference to the findings in Wilson precordial and Goldberger extremity leads. PMID- 21021609 TI - The total solids, fat and nitrogen in the feces of persons who have undergone partial gastrectomy with anastomosis of the entire cut end of the stomach to the jejunum (polya anastomosis). PMID- 21021610 TI - The effect of alumina gel upon the absorption of nutrient substances from the intestinal tract. PMID- 21021611 TI - Permanent residual damage in patients recovering from subacute bacterial endocarditis. PMID- 21021612 TI - Progression of tooth decay in presumably healthy children. PMID- 21021613 TI - An analysis of the subjective element in the clinical examination in nutrition. PMID- 21021614 TI - Effects of salicylates on the electrolytes of blood plasma. PMID- 21021615 TI - Active immunization of children with Shigella vaccines. PMID- 21021616 TI - Histamine and deafness. PMID- 21021617 TI - Clinical observations on the use of benadryl; a new antihistamine substance. PMID- 21021618 TI - Changes in blood coagulation following coronary thrombosis measured by the heparin retarded clotting test (Waugh and Ruddick test). PMID- 21021619 TI - The nutritional management of a patient with primary streptococcal peritonitis. PMID- 21021620 TI - A study of prothrombin activity and platelet counts in 61 patients with meningococcus meningitis. PMID- 21021621 TI - The faulty management of psychiatric disorders simulating organic disease. PMID- 21021622 TI - Absorption of large doses of orally administered penicillin. PMID- 21021623 TI - Pepsin-like substance in urine of patients with pernicious anemia and of normal subjects. PMID- 21021624 TI - St. Louis encephalitis. PMID- 21021625 TI - The effect of lipotropic substances and external biliary drainage on xanthomatous biliary cirrhosis. PMID- 21021626 TI - Breathholding; interchange of gases between the blood and lungs during voluntary breathholding and the factors which influence the maximum breathholding time. PMID- 21021627 TI - Rheumatic fever in Panama. PMID- 21021628 TI - The electrocardiographic effects of prostigmin. PMID- 21021629 TI - The influence of amino acids on voluntary food intake. PMID- 21021630 TI - A quantitative method for the measurement of water and heat loss from the respiratory tract of man, with studies of man in a subtropical climate. PMID- 21021631 TI - The use of tyrothricin in the treatment of surgical infections. PMID- 21021632 TI - Histamine in gelatine; observations on its use in allergic states and in various other clinical entities. PMID- 21021633 TI - The nature of urine volume effects in renal clearances. PMID- 21021634 TI - The angles of clearance used as a method for measuring cardiac size in children with rheumatic heart disease. PMID- 21021635 TI - Irreversible, toxic inclusion body anemia; a clinical and experimental study. PMID- 21021636 TI - The magnitude of salicylate hypoprothrombinemia. PMID- 21021637 TI - The question of a pulmono-coronary vagal reflex in experimental pulmonary embolism in dogs; an electrocardiographic study. PMID- 21021638 TI - [Not Available]. PMID- 21021639 TI - [Not Available]. PMID- 21021640 TI - [Not Available]. PMID- 21021641 TI - [Not Available]. PMID- 21021642 TI - [Not Available]. PMID- 21021643 TI - [Not Available]. PMID- 21021644 TI - [Not Available]. PMID- 21021645 TI - [Not Available]. PMID- 21021646 TI - [Not Available]. PMID- 21021647 TI - [Not Available]. PMID- 21021648 TI - [Not Available]. PMID- 21021649 TI - [Not Available]. PMID- 21021650 TI - [Not Available]. PMID- 21021651 TI - [Not Available]. PMID- 21021652 TI - [Not Available]. PMID- 21021653 TI - [Not Available]. PMID- 21021654 TI - [Not Available]. PMID- 21021655 TI - [Not Available]. PMID- 21021656 TI - [Not Available]. PMID- 21021657 TI - [Not Available]. PMID- 21021658 TI - [Not Available]. PMID- 21021659 TI - [Not Available]. PMID- 21021660 TI - [Not Available]. PMID- 21021661 TI - [Not Available]. PMID- 21021662 TI - [Not Available]. PMID- 21021663 TI - [Not Available]. PMID- 21021664 TI - [Not Available]. PMID- 21021665 TI - [Not Available]. PMID- 21021666 TI - [Not Available]. PMID- 21021667 TI - [Not Available]. PMID- 21021668 TI - [Not Available]. PMID- 21021669 TI - [Not Available]. PMID- 21021670 TI - [Not Available]. PMID- 21021671 TI - [Not Available]. PMID- 21021672 TI - [Not Available]. PMID- 21021673 TI - [Not Available]. PMID- 21021674 TI - [Not Available]. PMID- 21021675 TI - [Not Available]. PMID- 21021677 TI - [Not Available]. PMID- 21021676 TI - [Not Available]. PMID- 21021678 TI - [Not Available]. PMID- 21021679 TI - [Not Available]. PMID- 21021680 TI - [Not Available]. PMID- 21021681 TI - [Not Available]. PMID- 21021682 TI - [Not Available]. PMID- 21021683 TI - [Not Available]. PMID- 21021685 TI - [Not Available]. PMID- 21021684 TI - [Not Available]. PMID- 21021686 TI - [Not Available]. PMID- 21021687 TI - [Not Available]. PMID- 21021688 TI - [Not Available]. PMID- 21021689 TI - [Not Available]. PMID- 21021690 TI - [Not Available]. PMID- 21021691 TI - [Not Available]. PMID- 21021692 TI - [Not Available]. PMID- 21021693 TI - [Not Available]. PMID- 21021694 TI - [Not Available]. PMID- 21021695 TI - [Not Available]. PMID- 21021696 TI - [Not Available]. PMID- 21021697 TI - [Not Available]. PMID- 21021698 TI - [Not Available]. PMID- 21021699 TI - [Not Available]. PMID- 21021700 TI - [Not Available]. PMID- 21021701 TI - [Not Available]. PMID- 21021702 TI - [Not Available]. PMID- 21021703 TI - [Not Available]. PMID- 21021704 TI - [Not Available]. PMID- 21021705 TI - [Not Available]. PMID- 21021706 TI - [Not Available]. PMID- 21021708 TI - [Not Available]. PMID- 21021707 TI - [Not Available]. PMID- 21021709 TI - [Not Available]. PMID- 21021710 TI - [Not Available]. PMID- 21021711 TI - [Not Available]. PMID- 21021712 TI - [Not Available]. PMID- 21021714 TI - [Not Available]. PMID- 21021713 TI - [Not Available]. PMID- 21021715 TI - [Not Available]. PMID- 21021716 TI - [Not Available]. PMID- 21021717 TI - [Not Available]. PMID- 21021718 TI - [Not Available]. PMID- 21021719 TI - [Not Available]. PMID- 21021720 TI - [Not Available]. PMID- 21021722 TI - [Not Available]. PMID- 21021721 TI - [Not Available]. PMID- 21021723 TI - [Not Available]. PMID- 21021724 TI - [Not Available]. PMID- 21021725 TI - [Not Available]. PMID- 21021726 TI - [Not Available]. PMID- 21021727 TI - [Not Available]. PMID- 21021728 TI - [Not Available]. PMID- 21021729 TI - [Not Available]. PMID- 21021730 TI - [Not Available]. PMID- 21021731 TI - [Not Available]. PMID- 21021732 TI - A comparison of chemical and histological estimations of the iron and copper content of the livers of Africans in relation to the pathogenesis of cytosiderosis and cirrhosis (haemochromatosis). PMID- 21021733 TI - Rhesus blood groups in South African Europeans and South African Bantu. PMID- 21021734 TI - [Not Available]. PMID- 21021735 TI - [Not Available]. PMID- 21021736 TI - [Not Available]. PMID- 21021737 TI - [Not Available]. PMID- 21021738 TI - [Not Available]. PMID- 21021739 TI - [Not Available]. PMID- 21021740 TI - [Not Available]. PMID- 21021741 TI - [Not Available]. PMID- 21021742 TI - [Not Available]. PMID- 21021743 TI - [Not Available]. PMID- 21021745 TI - [Not Available]. PMID- 21021744 TI - [Not Available]. PMID- 21021746 TI - [Not Available]. PMID- 21021747 TI - [Not Available]. PMID- 21021748 TI - [Not Available]. PMID- 21021749 TI - [Not Available]. PMID- 21021750 TI - [Not Available]. PMID- 21021751 TI - [Not Available]. PMID- 21021752 TI - [Not Available]. PMID- 21021754 TI - Idiopathic ulcerative colitis. PMID- 21021753 TI - The start of State sanatoria. PMID- 21021755 TI - Herpes zoster. PMID- 21021756 TI - The use of red blood cell preparations. PMID- 21021757 TI - [Not Available]. PMID- 21021758 TI - [Not Available]. PMID- 21021760 TI - [Not Available]. PMID- 21021759 TI - [Not Available]. PMID- 21021761 TI - [Not Available]. PMID- 21021762 TI - [Not Available]. PMID- 21021763 TI - [Not Available]. PMID- 21021764 TI - [Not Available]. PMID- 21021765 TI - [Not Available]. PMID- 21021766 TI - [Not Available]. PMID- 21021767 TI - [Not Available]. PMID- 21021769 TI - [Not Available]. PMID- 21021768 TI - [Not Available]. PMID- 21021770 TI - [Not Available]. PMID- 21021771 TI - [Not Available]. PMID- 21021772 TI - [Not Available]. PMID- 21021773 TI - [Not Available]. PMID- 21021774 TI - [Not Available]. PMID- 21021775 TI - [Not Available]. PMID- 21021776 TI - [Not Available]. PMID- 21021778 TI - [Not Available]. PMID- 21021777 TI - [Not Available]. PMID- 21021779 TI - [Not Available]. PMID- 21021780 TI - [Not Available]. PMID- 21021781 TI - [Not Available]. PMID- 21021782 TI - [Not Available]. PMID- 21021783 TI - [Not Available]. PMID- 21021784 TI - [Not Available]. PMID- 21021785 TI - [Not Available]. PMID- 21021786 TI - [Not Available]. PMID- 21021787 TI - [Not Available]. PMID- 21021788 TI - [Not Available]. PMID- 21021789 TI - [Not Available]. PMID- 21021790 TI - [Not Available]. PMID- 21021791 TI - [Not Available]. PMID- 21021792 TI - [Not Available]. PMID- 21021793 TI - [Not Available]. PMID- 21021794 TI - [Not Available]. PMID- 21021795 TI - [Not Available]. PMID- 21021796 TI - [Not Available]. PMID- 21021797 TI - [Not Available]. PMID- 21021798 TI - [Not Available]. PMID- 21021799 TI - The Rh factor and erythroblastosis foetalis. PMID- 21021801 TI - Endometriosis. PMID- 21021800 TI - Thyrotoxicosis. PMID- 21021802 TI - Carbon monoxide anoxemia. PMID- 21021803 TI - [Not Available]. PMID- 21021804 TI - [Not Available]. PMID- 21021805 TI - [Not Available]. PMID- 21021806 TI - [Not Available]. PMID- 21021807 TI - [Not Available]. PMID- 21021808 TI - [Not Available]. PMID- 21021809 TI - [Not Available]. PMID- 21021810 TI - [Not Available]. PMID- 21021811 TI - [Not Available]. PMID- 21021812 TI - [Not Available]. PMID- 21021813 TI - [Not Available]. PMID- 21021814 TI - [Not Available]. PMID- 21021815 TI - [Not Available]. PMID- 21021816 TI - Acute porphyria with changes in the coeliac ganglion and prominent abdominal symptoms. PMID- 21021817 TI - The Weil-Felix reaction in typhus fever. PMID- 21021818 TI - [Not Available]. PMID- 21021819 TI - On the quantitative relationship between the lymphoid organs and the blood lymphocytes in the albino rat. PMID- 21021820 TI - On the presence of mast cells in thyroid glands from guinea-pig and from man, under different conditions. PMID- 21021821 TI - Studies on the basal phenol-resistant microbes in human faeces. PMID- 21021822 TI - Experimental investigations on the influence of estrogen on calcium metabolism. PMID- 21021823 TI - Pathological changes observed in a case of acute ascending paralysis complicating measles. PMID- 21021824 TI - A systematic study of Fusobacterium and Necrobacterium (i. e. Actinomyces necrophorus, Nekrosebacillus Bang) as to their biological relationships and proposal of a new and adequate name for the latter. PMID- 21021825 TI - Serum albumin and serum globulin after intravenous injection of large amounts of globulin and albumin; a hypothesis about the regulations of the colloid-osmotic pressure of the blood. PMID- 21021826 TI - Genetic aspects of osteochondrodystrophy; Silfverskiold's and Morquio's syndromes. PMID- 21021827 TI - Case of cor pseudobiloculare with situs inversus and transposition of the arteries. PMID- 21021828 TI - Variations in the virulence of pneumococci on passage in vitro. PMID- 21021829 TI - Studies on the durability of pneumococcus vaccines. PMID- 21021830 TI - Antibacterial effects of iodinin, 2-methylquinoxaline di-n-oxide and 2,6 dimethoxybenzoquinone in vitro. PMID- 21021831 TI - Biological observations upon Enterobius vermicularis (pinworm). PMID- 21021832 TI - Studies on induced resistance to penicillin in a pneumococcus type I. PMID- 21021833 TI - Change of type in the virus of foot-and-mouth disease observed in connection with artificial drying of the virus. PMID- 21021835 TI - A note on the coccidium Klossiella muris. PMID- 21021834 TI - Gaffkya tetragena isolated from a case of vitium organicum cordis congenitum combined with purpura thrombocytopenica. PMID- 21021836 TI - [Not Available]. PMID- 21021837 TI - Experimental investigation on the radio-sensitivity of the hypophysis. PMID- 21021838 TI - Effect of penicillin on leptospirae in vitro and on leptospirosis in guinea pigs. PMID- 21021839 TI - Autotransplantation of tarred skin to the anterior chamber of the eye; experimental contribution to the knowledge of latent neoplastic conditions. PMID- 21021840 TI - The vascular supply of tumours with special reference to the capillary angioarchitekture. PMID- 21021841 TI - The renal clearance of pantothenic acid. PMID- 21021842 TI - The nature of volume effects in renal clearances. PMID- 21021843 TI - Effect of protein deficiency and cholesterol feeding on the liver of dogs. PMID- 21021844 TI - Experimental lipemia and hypercholesterolemia by protein depletion and by cholesterol feeding in dogs. PMID- 21021845 TI - The importance of exogenous fat in fatty infiltration of the liver of dogs. PMID- 21021846 TI - The relative sensitivity of the mucosal and peritoneal surfaces of guinea-pig ileum to histamine, acetylcholine and specific antigens. PMID- 21021847 TI - Compensatory growth of the kidney after unilateral nephrectomy in thyroidectomized rats. PMID- 21021848 TI - Blood oxygen saturations and duration of consciousness in anoxia at high altitudes. PMID- 21021849 TI - The effects of feeding thyroid substances and of adrenalectomy on the activities of succinoxidase and cytochrome oxidase in the liver tissue of rats. PMID- 21021850 TI - Renal blood flow and renal clearance during hemorrhagic shock. PMID- 21021851 TI - The initiation of sweating in response to heat. PMID- 21021852 TI - The estimation of the cutaneous blood flow with the photoelectric plethysmograph. PMID- 21021853 TI - Diphenylamine as colorimetric agent in the determination of glycogen. PMID- 21021854 TI - Changes in the glycogen and water content of the rat uterus. PMID- 21021855 TI - Physiological factors affecting the production of gas bubbles in rabbits decompressed to altitude. PMID- 21021856 TI - Bubble formation in rabbits decompressed to altitude; effect of preoxygenation, electrical stimulation, and some pharmacological factors. PMID- 21021857 TI - Biochemical and physiological differentiation during morphogenesis; succinic dehydrogenase and succinoxidase in the cerebral cortex of the fetal pig. PMID- 21021858 TI - Effect of a respiratory enzyme system and creatine upon the growth of cells in vitro. PMID- 21021859 TI - The influence of temperature upon the oxygen consumption of several arthropods. PMID- 21021860 TI - The excretion of estrogens by the aglomerular kidney. PMID- 21021861 TI - Sensitization of cells to heat by visible light in presence of photodynamic dyes. PMID- 21021862 TI - The mechanism of the inhibition of hemolysis; inhibitory processes occurring in the course of simple hemolytic reactions. PMID- 21021863 TI - Proteolytic enzymes; the control of their activity. PMID- 21021864 TI - Proteolytic enzymes; the physiological significance of the control of their activity, especially with respect to bacterial growth. PMID- 21021866 TI - [Not Available]. PMID- 21021865 TI - Nerve as model temperature end organ. PMID- 21021867 TI - [Not Available]. PMID- 21021868 TI - Some health problems of college women. PMID- 21021869 TI - Using pupil records in physical education. PMID- 21021870 TI - The diagnosis of pulmonary tuberculosis. PMID- 21021871 TI - The bacteriology of tuberculosis. PMID- 21021872 TI - [Not Available]. PMID- 21021873 TI - [Not Available]. PMID- 21021875 TI - [Not Available]. PMID- 21021876 TI - [Not Available]. PMID- 21021874 TI - [Not Available]. PMID- 21021877 TI - [Not Available]. PMID- 21021878 TI - [Not Available]. PMID- 21021879 TI - Sludge density control; with particular reference to return sludge chlorination. PMID- 21021880 TI - High capacity trickling filters; causes of inferior results. PMID- 21021881 TI - [Not Available]. PMID- 21021882 TI - [Not Available]. PMID- 21021883 TI - [Not Available]. PMID- 21021884 TI - [Not Available]. PMID- 21021885 TI - [Not Available]. PMID- 21021886 TI - [Not Available]. PMID- 21021887 TI - [Not Available]. PMID- 21021888 TI - [Not Available]. PMID- 21021889 TI - [Not Available]. PMID- 21021890 TI - [Not Available]. PMID- 21021891 TI - [Not Available]. PMID- 21021892 TI - [Not Available]. PMID- 21021893 TI - [Not Available]. PMID- 21021894 TI - [Not Available]. PMID- 21021895 TI - Commemorating a great discovery and half a century of its development; this x rays. PMID- 21021896 TI - X-ray technician organizations; their aims and their achievements. PMID- 21021897 TI - The American Registry of X-Ray Technicians; twenty-two years of achievement. PMID- 21021898 TI - X-ray horizons. PMID- 21021899 TI - Fashion parade of x-ray apparatus, 1895-1945. PMID- 21021900 TI - [Not Available]. PMID- 21021901 TI - [Not Available]. PMID- 21021902 TI - [Not Available]. PMID- 21021903 TI - [Not Available]. PMID- 21021904 TI - [Not Available]. PMID- 21021906 TI - [Not Available]. PMID- 21021905 TI - [Not Available]. PMID- 21021907 TI - [Not Available]. PMID- 21021908 TI - [Not Available]. PMID- 21021909 TI - [Not Available]. PMID- 21021910 TI - [Not Available]. PMID- 21021911 TI - [Not Available]. PMID- 21021912 TI - [Not Available]. PMID- 21021913 TI - [Not Available]. PMID- 21021914 TI - [Not Available]. PMID- 21021915 TI - [Not Available]. PMID- 21021916 TI - [Not Available]. PMID- 21021917 TI - [Not Available]. PMID- 21021918 TI - [Not Available]. PMID- 21021919 TI - [Not Available]. PMID- 21021920 TI - [Not Available]. PMID- 21021921 TI - [Not Available]. PMID- 21021922 TI - [Not Available]. PMID- 21021923 TI - [Not Available]. PMID- 21021925 TI - [Not Available]. PMID- 21021924 TI - [Not Available]. PMID- 21021926 TI - [Not Available]. PMID- 21021927 TI - [Not Available]. PMID- 21021928 TI - [Not Available]. PMID- 21021929 TI - [Not Available]. PMID- 21021930 TI - [Not Available]. PMID- 21021931 TI - [Not Available]. PMID- 21021932 TI - [Not Available]. PMID- 21021933 TI - [Not Available]. PMID- 21021934 TI - [Not Available]. PMID- 21021935 TI - [Not Available]. PMID- 21021936 TI - [Not Available]. PMID- 21021937 TI - [Not Available]. PMID- 21021938 TI - [Not Available]. PMID- 21021939 TI - [Not Available]. PMID- 21021941 TI - [Not Available]. PMID- 21021940 TI - [Not Available]. PMID- 21021942 TI - [Not Available]. PMID- 21021943 TI - [Not Available]. PMID- 21021944 TI - [Not Available]. PMID- 21021945 TI - [Not Available]. PMID- 21021946 TI - [Not Available]. PMID- 21021947 TI - [Not Available]. PMID- 21021948 TI - [Not Available]. PMID- 21021949 TI - [Not Available]. PMID- 21021950 TI - [Not Available]. PMID- 21021952 TI - [Not Available]. PMID- 21021951 TI - [Not Available]. PMID- 21021953 TI - [Not Available]. PMID- 21021954 TI - On the anatomy of the inguinohypogastric and inguinofemoral regions. PMID- 21021955 TI - Recurrent dislocations of the shoulder joint. PMID- 21021956 TI - Primary diverticulitis of the caecum. PMID- 21021957 TI - Hydronephrosis in one half of a horse-shoe kidney. PMID- 21021958 TI - First rib syndrome. PMID- 21021959 TI - Congenital cyst brain. PMID- 21021960 TI - Adenoma of pituitary. PMID- 21021961 TI - A case of congenital unilateral hydronephrotic ectopic kidney with calculi. PMID- 21021962 TI - Psycho-surgery. PMID- 21021963 TI - [Not Available]. PMID- 21021964 TI - [Not Available]. PMID- 21021965 TI - [Not Available]. PMID- 21021966 TI - [Not Available]. PMID- 21021967 TI - [Not Available]. PMID- 21021968 TI - [Not Available]. PMID- 21021969 TI - [Not Available]. PMID- 21021970 TI - [Not Available]. PMID- 21021971 TI - [Not Available]. PMID- 21021972 TI - [Not Available]. PMID- 21021973 TI - [Not Available]. PMID- 21021974 TI - [Not Available]. PMID- 21021975 TI - [Not Available]. PMID- 21021976 TI - [Not Available]. PMID- 21021977 TI - [Not Available]. PMID- 21021978 TI - [Not Available]. PMID- 21021979 TI - [Not Available]. PMID- 21021980 TI - [Not Available]. PMID- 21021981 TI - [Not Available]. PMID- 21021982 TI - [Not Available]. PMID- 21021983 TI - [Not Available]. PMID- 21021984 TI - [Not Available]. PMID- 21021985 TI - [Not Available]. PMID- 21021986 TI - [Not Available]. PMID- 21021987 TI - [Not Available]. PMID- 21021988 TI - [Not Available]. PMID- 21021989 TI - [Not Available]. PMID- 21021990 TI - [Not Available]. PMID- 21021991 TI - [Not Available]. PMID- 21021992 TI - [Not Available]. PMID- 21021993 TI - [Not Available]. PMID- 21021994 TI - [Not Available]. PMID- 21021995 TI - [Not Available]. PMID- 21021996 TI - [Not Available]. PMID- 21021997 TI - [Not Available]. PMID- 21021998 TI - [Not Available]. PMID- 21021999 TI - [Not Available]. PMID- 21022000 TI - [Not Available]. PMID- 21022001 TI - [Not Available]. PMID- 21022002 TI - [Not Available]. PMID- 21022003 TI - [Not Available]. PMID- 21022004 TI - [Not Available]. PMID- 21022006 TI - [Not Available]. PMID- 21022005 TI - [Not Available]. PMID- 21022007 TI - [Not Available]. PMID- 21022008 TI - [Not Available]. PMID- 21022009 TI - [Not Available]. PMID- 21022010 TI - [Not Available]. PMID- 21022011 TI - [Not Available]. PMID- 21022013 TI - [Not Available]. PMID- 21022012 TI - [Not Available]. PMID- 21022014 TI - [Not Available]. PMID- 21022015 TI - [Not Available]. PMID- 21022016 TI - Experimental induction of mammary cancer. PMID- 21022017 TI - Parental influence on mammary tumor incidence. PMID- 21022018 TI - The prognosis of benign lesions of the female breast. PMID- 21022019 TI - The bleeding nipple. PMID- 21022020 TI - Intraductal biopsy of certain pathological processes of the breast. PMID- 21022021 TI - Sarcoma of the breast. PMID- 21022022 TI - A histologic classification of carcinoma of the breast. PMID- 21022023 TI - A technique for radical mastectomy. PMID- 21022024 TI - The treatment of inoperable carcinoma of the breast with irradiation. PMID- 21022025 TI - The problem of local recurrence after radical mastectomy for carcinoma. PMID- 21022026 TI - Survival rates of radical mastectomy for unilateral and bilateral carcinoma of the breast. PMID- 21022027 TI - [Not Available]. PMID- 21022028 TI - [Not Available]. PMID- 21022029 TI - [Not Available]. PMID- 21022030 TI - [Not Available]. PMID- 21022031 TI - [Not Available]. PMID- 21022033 TI - [Not Available]. PMID- 21022032 TI - [Not Available]. PMID- 21022034 TI - [Not Available]. PMID- 21022035 TI - Comparative strength of muscles with similar function; a study on peripheral nerve injuries of the upper extremity. PMID- 21022036 TI - How to bring benefits of physical medicine to your own small town. PMID- 21022037 TI - EXERCISE machine for amputations below the knee. PMID- 21022038 TI - [Not Available]. PMID- 21022039 TI - National examination for tuberculosis; work of the Roentgen bus during the first 2 years (1941-1943). PMID- 21022040 TI - Indications calling for the suction-draining of cavities. PMID- 21022041 TI - [Not Available]. PMID- 21022042 TI - Cor pulmonale as a sequel of thoracoplasty. PMID- 21022044 TI - [Not Available]. PMID- 21022043 TI - [Not Available]. PMID- 21022045 TI - [Not Available]. PMID- 21022046 TI - [Not Available]. PMID- 21022047 TI - [Not Available]. PMID- 21022048 TI - [Not Available]. PMID- 21022049 TI - [Not Available]. PMID- 21022050 TI - [Not Available]. PMID- 21022051 TI - [Not Available]. PMID- 21022052 TI - [Not Available]. PMID- 21022053 TI - [Not Available]. PMID- 21022054 TI - [Not Available]. PMID- 21022055 TI - [Not Available]. PMID- 21022056 TI - [Not Available]. PMID- 21022057 TI - [Not Available]. PMID- 21022058 TI - [Not Available]. PMID- 21022059 TI - [Not Available]. PMID- 21022060 TI - [Not Available]. PMID- 21022061 TI - [Not Available]. PMID- 21022062 TI - [Not Available]. PMID- 21022063 TI - [Not Available]. PMID- 21022064 TI - [Not Available]. PMID- 21022065 TI - [Not Available]. PMID- 21022066 TI - [Not Available]. PMID- 21022067 TI - [Not Available]. PMID- 21022068 TI - [Not Available]. PMID- 21022069 TI - [Not Available]. PMID- 21022070 TI - [Not Available]. PMID- 21022071 TI - [Not Available]. PMID- 21022072 TI - [Not Available]. PMID- 21022073 TI - [Not Available]. PMID- 21022074 TI - [Not Available]. PMID- 21022075 TI - [Not Available]. PMID- 21022076 TI - [Not Available]. PMID- 21022077 TI - [Not Available]. PMID- 21022078 TI - [Not Available]. PMID- 21022079 TI - [Not Available]. PMID- 21022080 TI - [Not Available]. PMID- 21022081 TI - [Not Available]. PMID- 21022082 TI - [Not Available]. PMID- 21022083 TI - [Not Available]. PMID- 21022085 TI - [Not Available]. PMID- 21022084 TI - [Not Available]. PMID- 21022086 TI - [Not Available]. PMID- 21022087 TI - [Not Available]. PMID- 21022088 TI - [Not Available]. PMID- 21022089 TI - [Not Available]. PMID- 21022090 TI - [Not Available]. PMID- 21022091 TI - [Not Available]. PMID- 21022092 TI - [Not Available]. PMID- 21022093 TI - [Not Available]. PMID- 21022094 TI - [Not Available]. PMID- 21022095 TI - [Not Available]. PMID- 21022096 TI - [Not Available]. PMID- 21022097 TI - [Not Available]. PMID- 21022099 TI - Contribution to the etiology of acquired fibrosis of the bladder neck. PMID- 21022098 TI - True infective abacterial pyuria. PMID- 21022100 TI - The incidence of signs of renal injury following prolonged burial under debris in an unselected series of 764 airraid casualties admitted to hospital. PMID- 21022101 TI - Obstructive anuria, probably due to calculus. PMID- 21022102 TI - [Not Available]. PMID- 21022104 TI - [Not Available]. PMID- 21022103 TI - [Not Available]. PMID- 21022105 TI - [Not Available]. PMID- 21022106 TI - [Not Available]. PMID- 21022107 TI - [Not Available]. PMID- 21022108 TI - [Not Available]. PMID- 21022109 TI - [Not Available]. PMID- 21022110 TI - [Not Available]. PMID- 21022111 TI - [Not Available]. PMID- 21022112 TI - [Not Available]. PMID- 21022113 TI - [Not Available]. PMID- 21022114 TI - [Not Available]. PMID- 21022115 TI - [Not Available]. PMID- 21022116 TI - [Not Available]. PMID- 21022117 TI - [Not Available]. PMID- 21022118 TI - [Not Available]. PMID- 21022120 TI - [Not Available]. PMID- 21022119 TI - [Not Available]. PMID- 21022121 TI - [Not Available]. PMID- 21022122 TI - [Not Available]. PMID- 21022123 TI - [Not Available]. PMID- 21022124 TI - [Not Available]. PMID- 21022125 TI - [Not Available]. PMID- 21022127 TI - [Not Available]. PMID- 21022126 TI - [Not Available]. PMID- 21022128 TI - Thoughts on the control of brucellosis in cattle. PMID- 21022129 TI - Undulant fever caused by Brucella abortus strain 19. PMID- 21022130 TI - The uremia complex. PMID- 21022131 TI - Additional field outbreaks of coccidiosis in chickens due to Eimeria brunetti. PMID- 21022132 TI - Anesthesia in horses and swine. PMID- 21022134 TI - A bacteriological study of the infections which follow injury to the bovine udder. PMID- 21022133 TI - Some phases of sterility in cattle. PMID- 21022135 TI - The prognosis and treatment of mastitis. PMID- 21022136 TI - Results of examination and treatment of mastitis in the ambulatory clinic. PMID- 21022137 TI - The anthelmintic efficiency against sheep nematodes of copper-nicotine sulfate alone, and copper-nicotine sulfate in conjunction with phenothiazine in salt. PMID- 21022138 TI - A genetic analysis of human eye color. PMID- 21022139 TI - Analysis of body photographs of 175 college women. PMID- 21022140 TI - Skeletal change in ancient Greece. PMID- 21022141 TI - A new rule for predicting the occurrence of multiple births. PMID- 21022142 TI - New pseudophyllidean cestodes from the Great Lakes region; Diphyllobothrium oblongatum n. sp. from gulls. PMID- 21022143 TI - The genus Protostrongylus kamenskii, 1905 (Nematoda; Metas trongylidae), and its relatives; preliminary note. PMID- 21022144 TI - Alaria taxideae n. sp., from the badger and other mustelids. PMID- 21022145 TI - The effect of some aryl arsonic acids on experimental coccidiosis infection in chickens. PMID- 21022146 TI - Parasitic infections among natives of the Samarai District, Papua, New Guinea. PMID- 21022147 TI - A note on the problem of plague in Dakar, Senegal, French West Africa. PMID- 21022148 TI - A new anoplocephalid cestode, Andrya neotomae, from the wood rat Neotoma fuscipes. PMID- 21022149 TI - Culture experiments on intestinal flagellates; trichomonad and other flagellates obtained from man and certain rodents. PMID- 21022150 TI - Intestinal canthariasis due to Tenebrio molitor. PMID- 21022151 TI - Observations on the tropical rat mite, Liponyssus bacoti, as an ecto-parasite of laboratory animals and suggestions for its control. PMID- 21022152 TI - A comparison of the percentage development of a mouse strain of Hymenolepis in alcoholic and non-alcoholic rats and mice. PMID- 21022153 TI - Factors affecting the hatching of ova of Schistosoma japonicum. PMID- 21022154 TI - A redescription of Physaloptera limbata Leidy, 1856 (Nematoda: Physalopterinae). PMID- 21022155 TI - The effect of alcohol on the development of acquired immunity to Hymenolepis in mice. PMID- 21022156 TI - Plasmodium lacertiliae n. sp., and other saurian blood parasites from the New Guinea area. PMID- 21022157 TI - The preparation and demonstration of an antiserum for Trichinella spiralis. PMID- 21022158 TI - Notes on the Chinese species of the genus Phlebotomus; sandflies in Chungking, Szechuan, with description of a new species, Phlebotomus koloshanensis. PMID- 21022159 TI - A note on the noise-making ability of the tsetse-fly, Glossina palpalis Rob. Desv. (Diptera, Glossinidae), while in flight. PMID- 21022160 TI - Examination of tube-dwelling polychaete annelids for larval trematode infections. PMID- 21022161 TI - New host records for the trombiculid mite, Acariscus masoni Ewing. PMID- 21022162 TI - New records of Macracanthorhynchus hirudinaceus in Sciuridae. PMID- 21022163 TI - A review of mosquito work in a world at war in 1944. PMID- 21022164 TI - The disease malaria from the point of view of the practicing physician. PMID- 21022166 TI - Experiments using DDT for the control of resting adults of Anopheles quadrimaculatus Say. PMID- 21022165 TI - Progress in the development of DDT mosquito larvicides. PMID- 21022167 TI - The development of DDT as a mosquito control agent. PMID- 21022168 TI - Operational planning for the malaria control in war areas DDT residual house spraying program. PMID- 21022169 TI - Laboratory evaluation of chemicals for rendering fabric repellent to mosquitoes. PMID- 21022170 TI - Mosquito work in Passaic County. PMID- 21022171 TI - Mosquito control work in California in 1944. PMID- 21022172 TI - What is the outlook for the mosquito control specialist? PMID- 21022173 TI - Mosquito work on a war time basis, special problems and the manner in which they are being met in Norfolk. PMID- 21022174 TI - Mosquito control at the Naval Base, Norfolk, Virginia. PMID- 21022175 TI - Mosquito work on a wartime basis, special problems and the manner in which they are being met in Philadelphia. PMID- 21022176 TI - Mosquito work on a war time basis, special problems and manner in which they are being met in Delaware County, Pennsylvania. PMID- 21022177 TI - Mosquito work on a wartime basis, special problems and the manner in which they are being met in Nassau County. PMID- 21022178 TI - A technique for the laboratory rearing of Anopheles quadrimaculatus Say. PMID- 21022179 TI - Malaria in New Jersey in 1944. PMID- 21022180 TI - Entomological evaluations of control work on the malaria control in war areas program during 1944. PMID- 21022181 TI - Mosquito transmission of disease. PMID- 21022182 TI - Training and educational services on the malaria control in war areas program. PMID- 21022183 TI - Mosquito work in the other Americas. PMID- 21022184 TI - A summary of mosquito work in New Jersey in 1944. PMID- 21022185 TI - The need for mosquito control in Cumberland County. PMID- 21022186 TI - The mosquito control program in Camden County. PMID- 21022187 TI - The utilization of fish by a mosquito abatement district; their effectiveness and limitations. PMID- 21022188 TI - A possible new place for explosives in mosquito control practice. PMID- 21022189 TI - Mosquito work done by the Army in the Second Service Command with special reference to entomological phases. PMID- 21022190 TI - Malaria control in the northeastern states. PMID- 21022191 TI - Sprayers and dusters for dispersing insecticides and rodenticides. PMID- 21022192 TI - The Army's program to minimize the danger of introduction of mosquito-borne diseases by returning personnel. PMID- 21022193 TI - The mosquito and mosquito-borne disease problem in international airlines operation. PMID- 21022194 TI - Anti-malaria mosquito work in Maryland. PMID- 21022195 TI - Mosquito work on a wartime basis, special problems and the manner in which they are being met. PMID- 21022196 TI - The mosquito control and training program at Fort Dix in 1943. PMID- 21022197 TI - Human tolerance to centrifugal force repeated hourly throughout a day. PMID- 21022198 TI - Pharmacodynamic reactions of previously irradiated organisms. PMID- 21022199 TI - Righting activity in spinal and decerebrate cats after d-amphetamine. PMID- 21022200 TI - The delimitation of separately innervated regions of single skeletal muscles. PMID- 21022201 TI - Spinal and peripheral synaptic susceptibility to nembutal (sodium pentobarbital) as shown by vesicular responses. PMID- 21022202 TI - The urinary excretion of thiamine, pyramin (the pyrimidine-like component of thiamine) and riboflavin by man in semistarvation. PMID- 21022203 TI - Speed of response of arterial oxygen saturation to rapid change in equivalent altitude. PMID- 21022204 TI - Vitamin K and experimental renal hypertension. PMID- 21022205 TI - The effect of air movement on the loss of heat by evaporation, convection, and radiation from nude and clothed individuals. PMID- 21022206 TI - The effect of chloral hydrate on the gastric emptying time in man. PMID- 21022207 TI - The recruitment of blood from the spleen during hemorrhage. PMID- 21022208 TI - Cihuapahtli, an activator of uterine motility. [Montanoa tomentosa]. PMID- 21022209 TI - Reactions of the spinal cord to laminectomy. PMID- 21022210 TI - A comparative study of androgen and 17-ketosteroid excretion in men. PMID- 21022211 TI - The renal excretion and reabsorption of bicarbonate. PMID- 21022212 TI - Clinical gonadotropic therapy complicated by antihormone formation. PMID- 21022213 TI - Enumeration of functional sweat glands in the human. PMID- 21022214 TI - In vitro examination of synovial dynamics with a needle electrode. PMID- 21022215 TI - Influence of the vascular bed on the pattern of oxygen tension in the cerebral cortex. PMID- 21022216 TI - Adult antigens (or specific combining groups) in the egg, embryo and larva of the frog. PMID- 21022217 TI - Studies in the development of frog hybrids; embryonic development in the cross Rana pipiens female x Rana sylvatica male. PMID- 21022218 TI - The nervous system and regeneration of the forelimb of adult Triturus; the stimulating action of a regenerated motor supply. PMID- 21022219 TI - Differential growth of the epidermis in Amblystoma punctatum. PMID- 21022220 TI - Some effects of x-rays on development in Drosophila. PMID- 21022221 TI - [Not Available]. PMID- 21022222 TI - [Not Available]. PMID- 21022223 TI - [Not Available]. PMID- 21022224 TI - [Not Available]. PMID- 21022225 TI - The determination of chloral in technical chloral. PMID- 21022226 TI - A micro-diffusion method for the estimation of carbon monoxide in blood. PMID- 21022227 TI - The determination of auxins in soils: including a note on synthetic growth substances. PMID- 21022228 TI - Some physicochemical methods in microchemistry: viscosity, surface tension and refractive index. PMID- 21022229 TI - Surface tension. PMID- 21022230 TI - Refractive index. PMID- 21022231 TI - Micro-filtration, a review. PMID- 21022232 TI - Applications of the intermittent A. C. arc technique of spectrographic analysis. PMID- 21022233 TI - Note on commercial papaverine. PMID- 21022234 TI - The estimation of codeine in presence of creosote. PMID- 21022235 TI - The determination of citrate and tartrate. PMID- 21022236 TI - The control of delivery from burettes. PMID- 21022237 TI - A vacuum-operated circulating pump. PMID- 21022238 TI - A new synthesis of 4-quinazolones. PMID- 21022239 TI - Spectrophotometric studies of the oxidation of fats; oxygen absorption and chromophore production in fatty esters. PMID- 21022240 TI - Sugar interconversion under reducing conditions. PMID- 21022241 TI - N1-(amino-alkyl)-sulfanilamides and N1-(acetamidoalkyl)-sulfanilamides. PMID- 21022242 TI - Some basic barbituric acid derivatives. PMID- 21022243 TI - The autoxidation of quininone. PMID- 21022244 TI - Derivatives of 1,2,4-triazole and of pyrazole. PMID- 21022245 TI - Amines related to 2,5-dimethoxyphenethylamine; 2-hydroxy and 2-methoxy-5 methylphenylalkanolamines. PMID- 21022246 TI - The Poisson-Baltzmann equation derived from the transfer of momentum. PMID- 21022247 TI - Chain mechanisms for the reaction of chlorine and oxalic acid. PMID- 21022248 TI - The preparation of substituted diphenylethylamines and diphenylethanolamines. PMID- 21022249 TI - The preparation of D-rhamnose from methyl alpha-d-mannopyranoside. PMID- 21022250 TI - Preparation of new derivatives of diethylstilbestrol and hexestrol by the Claisen rearrangement. PMID- 21022251 TI - Studies in organic peroxides; t-butyl peresters. PMID- 21022252 TI - Studies in organic peroxides; t-amyl hydroperoxide and di-t-amyl peroxide. PMID- 21022253 TI - The glyoxalines; the bromination of 2-phenyl-4-benzal-5-glyoxalidone. PMID- 21022254 TI - Organo-silicon polymers; the cyclic dimethyl siloxanes. PMID- 21022255 TI - Preparation of 2,4,6-trichlorophenyl isocyanate. PMID- 21022256 TI - The identity and polymorphism of oleyldistearin from kokum butter. PMID- 21022257 TI - Flavanones and related compounds; the preparation of polyhydroxychalcones and flavanones. PMID- 21022258 TI - Flavanones and related compounds; the colored reduction products of polyhydroxyflavanones. PMID- 21022259 TI - Flavanones and related compounds; the reduction of luteolin and apigenin trimethyl ether with sodium amalgam. PMID- 21022260 TI - Steric deformation; the synthesis of N-methyl etioporphyrin. PMID- 21022261 TI - Thiamorpholines, oxides and dioxides. PMID- 21022262 TI - The reversible inactivation of gliotoxin by thiols. PMID- 21022263 TI - Methionine and isoleucine content of mammalian hemoglobins; its significance for nutritional and metabolic studies. PMID- 21022264 TI - Metabolic products of Aspergillus ustus. PMID- 21022265 TI - Acid catalysis in the formation of chloroamides from hypochlorous acid; N chlorination by hypochlorite ions and by acyl hypochlorites. PMID- 21022266 TI - New naphthalene derivatives structurally related to stilboestrol. PMID- 21022267 TI - p-aminobenzenesulphonamide derivatives of pyrimidine as antibacterial agents. PMID- 21022268 TI - New synthetic oestrogens; the synthesis of 4:4-dihydroxy-alpha:Beta:2:2 tetramethyldibenzyl. PMID- 21022269 TI - Some 5-spirothiazolidiones. PMID- 21022270 TI - New potential chemotherapeutic agents; derivatives of benziminazole. PMID- 21022272 TI - Trityl derivatives of xylofuranose. PMID- 21022271 TI - 6-aminoacetoveratrone and 5: 6-dimethoxy-3-methylanthranil. PMID- 21022273 TI - Synthesis of diaminoacridines. PMID- 21022274 TI - The chloroacetylation of guaiacol. PMID- 21022275 TI - The acetylation of some 5-aminoacridines. PMID- 21022276 TI - The reactivity of gamma-pyrone quaternary salts. PMID- 21022277 TI - Reactions of alkylisoformanilides; reactions with pyridinium salts. PMID- 21022278 TI - Physical properties and chemical constitution; aliphatic hydrocarbons. PMID- 21022279 TI - The structure of some electron-deficient molecules. PMID- 21022280 TI - The preparation of halogenated methoxybenzaldehydes and the demethylation of the corresponding benzil derivatives. PMID- 21022281 TI - The Frankfort-mandibular plane angle in orthodontic diagnosis, classification, treatment planning, and prognosis. PMID- 21022282 TI - The Frankfort-mandibular base angle in dentofacial esthetics and orthodontic prognosis. PMID- 21022283 TI - The impacted mandibular third molar. PMID- 21022284 TI - Effect of periapical processes of deciduous teeth on the buds of permanent teeth; pathological-clinical study. PMID- 21022285 TI - Spontaneous regeneration of bone following excision of section of the mandible. PMID- 21022286 TI - Fatal infection following tooth extraction; gangrenous stomatitis. PMID- 21022288 TI - Planning and designing partial dentures. PMID- 21022287 TI - Dermoid cyst in the floor of the mouth. PMID- 21022289 TI - Emergency repair for full upper denture. PMID- 21022290 TI - Genesis for the dental practitioner. PMID- 21022291 TI - Syphilis of the oral cavity. PMID- 21022292 TI - Ameloblastoma. PMID- 21022293 TI - Penicillin and other antibiotics in dentistry. PMID- 21022294 TI - The treatment of maxillofacial injuries in the Mediterranean theatre of war. PMID- 21022295 TI - A technique for investing wax patterns by vacuum. PMID- 21022296 TI - [Not Available]. PMID- 21022297 TI - [Not Available]. PMID- 21022298 TI - [Not Available]. PMID- 21022299 TI - [Not Available]. PMID- 21022300 TI - [Not Available]. PMID- 21022301 TI - [Not Available]. PMID- 21022302 TI - [Not Available]. PMID- 21022303 TI - [Not Available]. PMID- 21022304 TI - [Not Available]. PMID- 21022305 TI - [Not Available]. PMID- 21022306 TI - [Not Available]. PMID- 21022307 TI - [Not Available]. PMID- 21022308 TI - [Not Available]. PMID- 21022309 TI - [Not Available]. PMID- 21022310 TI - [Not Available]. PMID- 21022311 TI - [Not Available]. PMID- 21022312 TI - Nutritional status of Dutch children in wartime. PMID- 21022313 TI - PRESENT knowledge of carbohydrate in nutrition. PMID- 21022314 TI - L. casei factor in the treatment of macrocytic anemias. PMID- 21022315 TI - CHEMICAL determination of protein value. PMID- 21022316 TI - COLOR tests for vitamin A. PMID- 21022317 TI - HEMOGLOBIN and plasma protein production and the role of iron. PMID- 21022318 TI - VITAMIN inhibitors. PMID- 21022319 TI - MICROBIOLOGIC estimation of the essential amino acids. PMID- 21022320 TI - DENTAL caries in the rhesus monkey. PMID- 21022321 TI - NUTRIENTS formed by intestinal synthesis in animal diets. PMID- 21022322 TI - URINARY excretion of calcium and phosphorus following fracture. PMID- 21022323 TI - EDEMA during induced remissions in macrocytic anemia. PMID- 21022324 TI - TECHNICS for determining what people eat. PMID- 21022325 TI - EFFECTS of glucoascorbic acid. PMID- 21022326 TI - NITROGEN metabolism in typhus fever. PMID- 21022327 TI - URINARY coproporphyrin in nonalcoholic pellagrins. PMID- 21022328 TI - The composition and milling of wheat. PMID- 21022329 TI - Nutritive value of proteins contained in wheat flours of different degrees of extraction. PMID- 21022330 TI - Vitamin values of different types of flour. PMID- 21022331 TI - Enrichment. PMID- 21022332 TI - The value of wheat offals for milk production. PMID- 21022333 TI - Problems of stock feeding. PMID- 21022334 TI - Pasture and its dangers to livestock. PMID- 21022335 TI - Mineral deficiency conditions in sheep on Scottish hill grazings. PMID- 21022336 TI - Protein deficiency in man. PMID- 21022337 TI - Abdominal pain in pneumonia. PMID- 21022338 TI - The physiologic use of water in constipation. PMID- 21022339 TI - Vitamins and hormones in nutrition; endocrine dyscrasia. PMID- 21022340 TI - Redundancy of the colon. PMID- 21022341 TI - Silent gallstones. PMID- 21022342 TI - Geriatrics; the general setting. PMID- 21022343 TI - The incidence and treatment of delirious reactions in later life. PMID- 21022344 TI - Tuberculosis among persons over 50 years of age. PMID- 21022345 TI - Some American contributions to the literature of geriatrics. PMID- 21022346 TI - Geriatric anesthesia. PMID- 21022347 TI - Geriatrics and postwar problems. PMID- 21022348 TI - Mental disorders of old age. PMID- 21022349 TI - Bronchial asthma with special reference to its elderly victims. PMID- 21022350 TI - [Not Available]. PMID- 21022351 TI - [Not Available]. PMID- 21022352 TI - [Not Available]. PMID- 21022353 TI - [Not Available]. PMID- 21022354 TI - [Not Available]. PMID- 21022356 TI - Diabetes mellitus and pregnancy; a review. PMID- 21022355 TI - [Not Available]. PMID- 21022357 TI - [Not Available]. PMID- 21022358 TI - [Not Available]. PMID- 21022359 TI - [Not Available]. PMID- 21022360 TI - [Not Available]. PMID- 21022361 TI - [Not Available]. PMID- 21022362 TI - [Not Available]. PMID- 21022363 TI - [Not Available]. PMID- 21022364 TI - Pharmacopoeias as witnesses of world history. PMID- 21022365 TI - The two earliest dentistry woodcuts. PMID- 21022366 TI - Medical education in 17th century England. PMID- 21022367 TI - Incubator and taboo. PMID- 21022368 TI - Animal substances in materia medica; a study in the persistence of the primitive. PMID- 21022369 TI - A seven year study of premature babies, delivered from September 1, 1937 to September 1, 1944, at Hahnemann Hospital, Philadelphia, Pa. PMID- 21022370 TI - Common skin diseases of infants and children. PMID- 21022371 TI - Erythroblastosis fetalis. PMID- 21022372 TI - A report of an unusual case of influenzal meningitis with recovery. PMID- 21022374 TI - [Not Available]. PMID- 21022373 TI - [Not Available]. PMID- 21022375 TI - [Not Available]. PMID- 21022376 TI - [Not Available]. PMID- 21022377 TI - [Not Available]. PMID- 21022378 TI - [Not Available]. PMID- 21022379 TI - The course of filariasis after removal from an endemic area. PMID- 21022380 TI - The treatment of bacterial endocarditis with penicillin; results of 17 consecutive unselected cases. PMID- 21022381 TI - OBSERVATIONS on the treatment of scarlet fever with penicillin. PMID- 21022382 TI - Slowly progressive occlusive thrombosis of the abdominal portion of the aorta. PMID- 21022383 TI - Importance of urinary chloride determinations in treatment of patients having pyloric obstruction; a review of 50 cases of duodenal ulcer. PMID- 21022384 TI - Roentgen studies of the spleen. PMID- 21022385 TI - Emotional factors in obesity. PMID- 21022386 TI - The value of Speransky's method of spinal pumping in the treatment of rheumatic fever and rheumatoid arthritis. PMID- 21022387 TI - The change in plasma volume and body weight in normal subjects after a low salt diet, ammonium chloride and mercupurin. PMID- 21022388 TI - The relation of arterial pulse-pressure to arteriovenous oxygen difference, especially in arterial hypertension. PMID- 21022390 TI - Tumors of the skin; a review of recent literature. PMID- 21022389 TI - The agglutination reaction for hemolytic streptococci in rheumatoid arthritis; its significance in diagnosis and treatment. PMID- 21022391 TI - Cigarette smoke, irritation and the throat. PMID- 21022392 TI - Idiosyncratic febrile reactions to thiouracil; clinical characteristics and possible pharmacologic significance. PMID- 21022393 TI - Meningococcic infections with special reference to certain diagnostic considerations; an analysis of thirty-seven cases. PMID- 21022394 TI - Chronic hemolytic anemia with paroxysmal nocturnal hemoglobinuria. PMID- 21022396 TI - Broncholithiasis; report of ten cases. PMID- 21022395 TI - Infectious mononucleosis; a clinical study of sixty-three cases. PMID- 21022397 TI - Amebiasis; a report of thirty-nine cases observed in an Army general hospital stationed in Northern Ireland. PMID- 21022398 TI - Hypersensitivity and rheumatic fever. PMID- 21022399 TI - The value of penicillin in the control of sepsis complicating a case of severe granulocytopenia (aleukemic leukemia). PMID- 21022400 TI - Back pain as a symptom of carcinoma of the body of the pancreas. PMID- 21022401 TI - Follicular lymphoma (Brill-Symmers disease) unsuccessfully treated with penicillin. PMID- 21022402 TI - The use of penicillin in agranulocytosis. PMID- 21022403 TI - Fonocardiografia. PMID- 21022404 TI - Acute segmental enteritis. PMID- 21022405 TI - [Not Available]. PMID- 21022407 TI - Gastroscopy; a survey. PMID- 21022406 TI - [Not Available]. PMID- 21022408 TI - Acute inversion of the uterus following delivery. PMID- 21022409 TI - Observations on some rock carvings of surgical instruments in East Africa. PMID- 21022410 TI - Industrial accidents and new legislation; some implications of the National Insurance (Industrial Injuries) Bill, 1945. PMID- 21022411 TI - Thiouracil in the treatment of thyrotoxicosis; further experiences. PMID- 21022412 TI - Out-patient treatment of early syphilis with penicillin; a survey of 215 cases treated by single daily injections. PMID- 21022413 TI - A case of periarteritis nodosa; the role of anaphylaxis. PMID- 21022414 TI - A case of metastatic gas gangrene. PMID- 21022415 TI - Significance of symptoms in the diagnosis of pulmonary tuberculosis. PMID- 21022416 TI - Long-standing dislocation of mandible; manual reduction. PMID- 21022417 TI - An excision knife for tropical ulcers. PMID- 21022418 TI - Naples typhus epidemic, 1942-3. PMID- 21022419 TI - Staple introducer for recurrent shoulder dislocation. PMID- 21022420 TI - Coarctation of the aorta. PMID- 21022421 TI - [Not Available]. PMID- 21022422 TI - [Not Available]. PMID- 21022423 TI - [Not Available]. PMID- 21022424 TI - [Not Available]. PMID- 21022425 TI - [Not Available]. PMID- 21022426 TI - [Not Available]. PMID- 21022427 TI - [Not Available]. PMID- 21022428 TI - Management and treatment of syphilis. PMID- 21022429 TI - Study of anemia. PMID- 21022430 TI - [Not Available]. PMID- 21022431 TI - [Not Available]. PMID- 21022432 TI - [Not Available]. PMID- 21022433 TI - Anesthetic mortality and morbidity; causes and avoidance; the place of the general practitioner in anesthesia. PMID- 21022435 TI - Functional neurosis; the crux of the physician. PMID- 21022434 TI - High blood pressure; clinical importance of ophthalmoscopy. PMID- 21022436 TI - The diagnosis of appendicitis. PMID- 21022437 TI - Rheumatic fever; functional systolic murmur. PMID- 21022438 TI - Inflammatory urethral strictures; a simple method of dilatation. PMID- 21022439 TI - Empyema: diagnosis and treatment. PMID- 21022440 TI - Common errors in diagnostic roentgenology. PMID- 21022442 TI - [Not Available]. PMID- 21022441 TI - [Not Available]. PMID- 21022443 TI - [Not Available]. PMID- 21022444 TI - [Not Available]. PMID- 21022445 TI - [Not Available]. PMID- 21022446 TI - [Not Available]. PMID- 21022447 TI - [Not Available]. PMID- 21022448 TI - [Not Available]. PMID- 21022449 TI - [Not Available]. PMID- 21022450 TI - [Not Available]. PMID- 21022451 TI - [Not Available]. PMID- 21022453 TI - [Not Available]. PMID- 21022452 TI - [Not Available]. PMID- 21022454 TI - [Not Available]. PMID- 21022455 TI - [Not Available]. PMID- 21022456 TI - [Not Available]. PMID- 21022457 TI - [Not Available]. PMID- 21022458 TI - [Not Available]. PMID- 21022459 TI - [Not Available]. PMID- 21022460 TI - [Not Available]. PMID- 21022461 TI - [Not Available]. PMID- 21022462 TI - [Not Available]. PMID- 21022463 TI - [Not Available]. PMID- 21022464 TI - [Not Available]. PMID- 21022465 TI - [Not Available]. PMID- 21022466 TI - [Not Available]. PMID- 21022468 TI - [Not Available]. PMID- 21022467 TI - [Not Available]. PMID- 21022469 TI - [Not Available]. PMID- 21022470 TI - [Not Available]. PMID- 21022471 TI - [Not Available]. PMID- 21022472 TI - [Not Available]. PMID- 21022473 TI - [Not Available]. PMID- 21022474 TI - [Not Available]. PMID- 21022475 TI - [Not Available]. PMID- 21022476 TI - [Not Available]. PMID- 21022477 TI - [Not Available]. PMID- 21022478 TI - [Not Available]. PMID- 21022479 TI - [Not Available]. PMID- 21022480 TI - [Not Available]. PMID- 21022481 TI - [Not Available]. PMID- 21022482 TI - [Not Available]. PMID- 21022483 TI - [Not Available]. PMID- 21022485 TI - [Not Available]. PMID- 21022484 TI - [Not Available]. PMID- 21022486 TI - [Not Available]. PMID- 21022487 TI - [Not Available]. PMID- 21022488 TI - [Not Available]. PMID- 21022489 TI - [Not Available]. PMID- 21022491 TI - Traumatic aneurysm and arteriovenous fistula. PMID- 21022490 TI - [Not Available]. PMID- 21022492 TI - Types of aneurysm; their diagnosis and treatment. PMID- 21022493 TI - [Not Available]. PMID- 21022495 TI - [Not Available]. PMID- 21022494 TI - [Not Available]. PMID- 21022496 TI - [Not Available]. PMID- 21022497 TI - [Not Available]. PMID- 21022499 TI - [Not Available]. PMID- 21022498 TI - [Not Available]. PMID- 21022500 TI - [Not Available]. PMID- 21022501 TI - [Not Available]. PMID- 21022502 TI - [Not Available]. PMID- 21022503 TI - [Not Available]. PMID- 21022504 TI - [Not Available]. PMID- 21022505 TI - [Not Available]. PMID- 21022506 TI - [Not Available]. PMID- 21022507 TI - [Not Available]. PMID- 21022508 TI - [Not Available]. PMID- 21022510 TI - [Not Available]. PMID- 21022509 TI - [Not Available]. PMID- 21022511 TI - [Not Available]. PMID- 21022512 TI - [Not Available]. PMID- 21022513 TI - [Not Available]. PMID- 21022514 TI - Carcinoma of the apex of the lung with Horner's syndrome. PMID- 21022515 TI - Penicillin in cancrum oris complicating kala-azar. PMID- 21022516 TI - A case of multiple primary carcinomata. PMID- 21022517 TI - A ballon cyst of the lung. PMID- 21022518 TI - The complement-fixation reaction in gonorrhoea. PMID- 21022519 TI - Pneumo-peritoneum in the investigation of the right costohepatic area. PMID- 21022520 TI - Sulphamezathine in the treatment of cerebro-spinal meningitis. PMID- 21022521 TI - Paralysis of neck muscles in poliomyelitis. PMID- 21022522 TI - Infective hepatitis among Indians. PMID- 21022523 TI - The treatment of kala-azar with sodium antimony-v-gluconate; preliminary observations. PMID- 21022524 TI - Parenteric fever due to Bacterium faecalis alkaligenes. PMID- 21022525 TI - On three cases of idiosyncratic urticaria in course of relapsing malaria. PMID- 21022526 TI - Malaria contracted after splenectomy for splenomegaly probably caused by kala azar. PMID- 21022527 TI - Some aspects of malaria therapy on the eastern frontier of India, 1942-44. PMID- 21022528 TI - Disposal of night-soil and rubbish by compost system. PMID- 21022529 TI - Acute surgical thrombotic emergencies. PMID- 21022530 TI - Thrombocytopenic purpura following angina; report of fatal case with autopsy. PMID- 21022531 TI - Allergic iritis. PMID- 21022533 TI - Therapeutic techniques used with a special group of disturbed children. PMID- 21022532 TI - Urologic neurosis and psychoses. PMID- 21022534 TI - The problem of primary lateral sclerosis. PMID- 21022535 TI - Physical reconditioning after rheumatic fever. PMID- 21022536 TI - Faulty management of psychiatric syndromes simulating organic disease. PMID- 21022537 TI - Vitamin D intoxication with metastatic calcification. PMID- 21022538 TI - The psychosomatic aspects of sterility. PMID- 21022539 TI - Nodular nonsuppurative panniculitis treated with penicillin. PMID- 21022540 TI - Mycotic aneurysm of the ulnar artery. PMID- 21022541 TI - Acute acetone poisoning from leg casts of a synthetic plaster substitute. PMID- 21022542 TI - WAGNER-MURRAY-DINGELL Bill. PMID- 21022543 TI - Typhus fever; with special reference to its incidence in India. PMID- 21022544 TI - A further note on the treatment of black water fever with antivenene. PMID- 21022545 TI - Maternal mortality. PMID- 21022546 TI - Sulphonamides in ophthalmic practice. PMID- 21022547 TI - Observations on capillary and venous blood in traumatic shook. PMID- 21022548 TI - Studies in complement fixation; preservation of sheep's blood in citrate dextrose mixtures (modified Alsever's solution) for use in the complement fixation reaction. PMID- 21022549 TI - Homologous and heterologous strains of Plasmodium vivax; a cross-inoculation study of malaria strain immunity. PMID- 21022550 TI - Bacteriologic studies of the sputum in patients with pneumococcal pneumonia treated with penicillin. PMID- 21022551 TI - Production of anemia in a pig which responded to purified liver extract. PMID- 21022552 TI - The relation of the plasma salicylate level to the degree of hypoprothrombinemia. PMID- 21022553 TI - A critical analysis of the value of the addition of A and B group-specific substances to group O blood for use as universal donor blood. PMID- 21022555 TI - A clinical method of determining the specific renal functions of glomerular filtration and maximal tubular excretion, or reabsorption (and effective blood flow), using a single injection of a single substance. PMID- 21022554 TI - Urea as an adjunct to sulfonamide therapy. PMID- 21022556 TI - A comparative study of mercuhydrin and mercupurin, oral and parenteral. PMID- 21022557 TI - The effect of theophylline aminoisobutanol in the failing experimental heart. PMID- 21022558 TI - Effect of stimuli originating in the upper abdomen in the causation of reflex shortening of the esophagus. PMID- 21022559 TI - Sulfathalidine; further studies on clinical, chemical, and bacteriologic evaluation in infectious diseases of the colon. PMID- 21022560 TI - The detection of dangerous carriers of hemolytic streptococci by the measurement of their streptococcal output. PMID- 21022561 TI - Antipneumococcus hyaluronidase activity in human serum; rise in titer following pneumococcus bacteremia with purulent infection of pleura and synovia. PMID- 21022562 TI - The effect of superimposed bacterial pneumonia on the severity of sublethal infection with influenza virus. PMID- 21022563 TI - The significance of the accessory spleen. PMID- 21022564 TI - Observations on the effect of massive doses of iron given intravenously to patients with hypochromic anemia. PMID- 21022565 TI - The action of various drugs on the prothrombin of the blood. PMID- 21022566 TI - The effect of thiouracil on leucemia with a clinico-pathologic report of a case of chronic myeloid leucemia that developed an extreme neutropenic leucopenia. PMID- 21022567 TI - Reactions from universal donor blood. PMID- 21022568 TI - Effect of resuspended erythrocyte transfusion on serum protein. PMID- 21022569 TI - The syndrome of hyperventilation. PMID- 21022570 TI - Metabolic and physical changes associated with the oral and intravenous administration of amino acid preparations to man. PMID- 21022571 TI - Phospholipids of liver and blood studied with radioactive phosphorus. PMID- 21022572 TI - Sequelae of trench foot and their treatment by lumbar sympathectomy. PMID- 21022573 TI - Toxic manifestations following large doses of ertron. PMID- 21022574 TI - The effect of infection and trauma on the excretion of urinary cortin. PMID- 21022576 TI - Changes in the prominence of the eyes in various thyroid states. PMID- 21022575 TI - The effect of diet on the growth and survival of adrenalectomized rats treated with desoxycorticosterone acetate pellets. PMID- 21022577 TI - The clinical significance of the functional behavior of adenomas of the thyroid gland. PMID- 21022578 TI - The effect of salicylate on the sedimentation rate, fever, and occurrence of valvular heart disease in acute rheumatic fever. PMID- 21022579 TI - Penicillin and dicumarol, and penicillin in the treatment of subacute bacterial endocarditis. PMID- 21022580 TI - A study of beriberi heart disease at the Cincinnati General Hospital. PMID- 21022581 TI - Follow-up studies of patients with cardiac wounds. PMID- 21022582 TI - The precordial electrocardiogram in high lateral myocardial infarction. PMID- 21022583 TI - Electrocardiographic diagnosis of right ventricular lesions with especial reference to the findings in the Wilson precordial and Goldberger extremity leads. PMID- 21022584 TI - Irreversible and slowly reversible changes in severe malnutrition. PMID- 21022585 TI - The total solids, fat, and nitrogen in the feces of persons who have undergone partial gastrectomy with anastomosis of the entire cut end of the stomach to the jejunum (polya anastomosis). PMID- 21022586 TI - The effect of alumina gel upon the absorption of nutrient substances from the intestinal tract. PMID- 21022587 TI - The new Mental Treatment Act. PMID- 21022588 TI - The bleeding breast. PMID- 21022589 TI - NOTE (A) on tests of renal function. PMID- 21022590 TI - Sublingual administration of penicillin. PMID- 21022591 TI - Cough in tuberculosis. PMID- 21022592 TI - Shock therapy at the Essex County Hospital. PMID- 21022593 TI - The wart and its treatment. PMID- 21022594 TI - Masking of mastoiditis symptoms by penicillin. PMID- 21022595 TI - The treatment of amebiasis. PMID- 21022596 TI - Asymptomatic congenital diaphragmatic hernia; a case report. PMID- 21022597 TI - [Not Available]. PMID- 21022598 TI - [Not Available]. PMID- 21022599 TI - [Not Available]. PMID- 21022600 TI - [Not Available]. PMID- 21022601 TI - [Not Available]. PMID- 21022602 TI - [Not Available]. PMID- 21022603 TI - [Not Available]. PMID- 21022604 TI - [Not Available]. PMID- 21022605 TI - [Not Available]. PMID- 21022606 TI - [Not Available]. PMID- 21022607 TI - [Not Available]. PMID- 21022608 TI - [Not Available]. PMID- 21022609 TI - [Not Available]. PMID- 21022610 TI - [Not Available]. PMID- 21022611 TI - [Not Available]. PMID- 21022612 TI - [Not Available]. PMID- 21022614 TI - [Not Available]. PMID- 21022613 TI - L'aspiration endo-cavitaire. PMID- 21022615 TI - [Not Available]. PMID- 21022616 TI - [Not Available]. PMID- 21022617 TI - [Not Available]. PMID- 21022618 TI - [Not Available]. PMID- 21022619 TI - [Not Available]. PMID- 21022620 TI - [Not Available]. PMID- 21022621 TI - [Not Available]. PMID- 21022622 TI - [Not Available]. PMID- 21022623 TI - [Not Available]. PMID- 21022624 TI - Anal cryptitis; its relation to focal infection, fissure and fistula. PMID- 21022625 TI - [Not Available]. PMID- 21022626 TI - The diagnosis and treatment of meningitis. PMID- 21022627 TI - The epidemiology of tinea capitis in Detroit school children. PMID- 21022629 TI - Tidal irrigation following gynecological operations. PMID- 21022628 TI - The effects of small doses of penicillin administered to patients with undiagnosed early syphilis; report of three cases. PMID- 21022630 TI - The management of common skin diseases. PMID- 21022631 TI - Herpes simplex. PMID- 21022632 TI - Poliomyelitis; failure of intrauterine fetal transmission. PMID- 21022633 TI - Caffeine. PMID- 21022634 TI - Lung sarcoma. PMID- 21022635 TI - Topographical studies in leishmaniasis in Palestine. PMID- 21022636 TI - The rupture of the coronary arteries. PMID- 21022637 TI - A plasmocytome of the nose and naso-pharynx. PMID- 21022638 TI - Eosinophilic infiltration of the lung; report on two cases. PMID- 21022640 TI - This is our medical profession. PMID- 21022639 TI - Privin, a substitute for adrenaline in ear, nose and throat diseases. PMID- 21022641 TI - The American Medical Association, what, why, and who. PMID- 21022642 TI - Beta-hemolytic streptococcic septicemia, acute bacterial endocarditis, acute mastoiditis and embolic brain abscess successfully treated with sulfadiazine and penicillin; report of case. PMID- 21022643 TI - Acute thyroiditis treated with penicillin. PMID- 21022644 TI - SOCIALIZED medicine. PMID- 21022645 TI - Clinical pathology; past and future. PMID- 21022646 TI - Neuronal damage from temporary cardiac arrest. PMID- 21022647 TI - Acute necrosis of the liver treated with protein hydrolysates. PMID- 21022648 TI - Toxicity of marfanil and V187 to cells in vitro. PMID- 21022649 TI - Tuberculous lobar pneumonia treated by pneumoperitoneum and phrenic crush. PMID- 21022650 TI - Peptic oesophageal ulcer; nonfatal perforation. PMID- 21022651 TI - Osteomyelitis, radiographically resembling sarcoma. PMID- 21022652 TI - Double-exposure radiograms of chest. PMID- 21022653 TI - Cerebral cysticercosis without epilepsy. PMID- 21022654 TI - Famine and malnutrition in Europe. PMID- 21022655 TI - WORLD food shortage. PMID- 21022656 TI - Biological effects of high-frequency currents. PMID- 21022657 TI - Place of medical societies in the doctor's life. PMID- 21022658 TI - One-shot treatment of acute gonorrhoea with penicillin; review of 617 male cases. PMID- 21022659 TI - Air-embolism and pneumomediastinum in artificial pneumoperitoneum. PMID- 21022660 TI - Pulmonary oedema in chest wounds. PMID- 21022662 TI - PERIODICITY OF influenza. PMID- 21022661 TI - Mesenteric venous thrombosis; recovery after resection with heparin. PMID- 21022664 TI - [Not Available]. PMID- 21022663 TI - Blood-transfusion in maxillofacial injury. PMID- 21022665 TI - [Not Available]. PMID- 21022666 TI - [Not Available]. PMID- 21022667 TI - [Not Available]. PMID- 21022668 TI - [Not Available]. PMID- 21022669 TI - [Not Available]. PMID- 21022670 TI - [Not Available]. PMID- 21022671 TI - Myocardial infarction in Negroes. PMID- 21022672 TI - Children in wartime. PMID- 21022674 TI - [Not Available]. PMID- 21022673 TI - Gastroscopy in the differential diagnosis of gastric ulcer. PMID- 21022675 TI - [Not Available]. PMID- 21022676 TI - [Not Available]. PMID- 21022677 TI - [Not Available]. PMID- 21022678 TI - [Not Available]. PMID- 21022679 TI - [Not Available]. PMID- 21022680 TI - [Not Available]. PMID- 21022681 TI - [Not Available]. PMID- 21022682 TI - [Not Available]. PMID- 21022683 TI - [Not Available]. PMID- 21022684 TI - [Not Available]. PMID- 21022685 TI - [Not Available]. PMID- 21022686 TI - [Not Available]. PMID- 21022687 TI - [Not Available]. PMID- 21022689 TI - [Not Available]. PMID- 21022688 TI - [Not Available]. PMID- 21022690 TI - [Not Available]. PMID- 21022691 TI - [Not Available]. PMID- 21022692 TI - [Not Available]. PMID- 21022693 TI - [Not Available]. PMID- 21022694 TI - [Not Available]. PMID- 21022695 TI - Acute porphyria, with reports of two fatal cases. PMID- 21022696 TI - A note on the use of penicillin in the laboratory diagnosis of whooping cough. PMID- 21022697 TI - Epidemic polyarthritis. PMID- 21022698 TI - Moulds in the lungs. PMID- 21022699 TI - Spondylitis ankylopoietica. PMID- 21022700 TI - Treatment of gunshot wounds of the chest in the field aided by penicillin therapy. PMID- 21022701 TI - A case of periarteritis (polyarteritis) nodosa. PMID- 21022702 TI - Local amputation of gangrenous toes in the presence of glycosuria and senility. PMID- 21022703 TI - NEUROSYPHILIS: dementia paralytica. PMID- 21022704 TI - DISSEMINATED sclerosis. PMID- 21022705 TI - HUNTINGTON'S chorea. PMID- 21022706 TI - ORGANIC brain disease, possibly cerebral tumor. PMID- 21022707 TI - ANOREXIA nervosa. PMID- 21022708 TI - Enteric fever due to Bacterium enteritidis var. blegdam (Salmonella blegdam); a series of fifty cases in Australian soldiers from New Gui nea. PMID- 21022709 TI - Preliminary report on strains of Salmonella blegdam causing infections in humans in New Guinea. PMID- 21022710 TI - The sociological aspects of community housing. PMID- 21022711 TI - Compound fractures of the extremities due to gunshot wounds; the early results of treatment in the field aided by penicillin therapy. PMID- 21022712 TI - A case of Addison's suprarenal syndrome of primary pituitary origin. PMID- 21022713 TI - Wounds caused by small fish. PMID- 21022714 TI - Radiology in the diagnosis of bone tumors. PMID- 21022716 TI - A family health centre. PMID- 21022715 TI - Dentistry in general practice. PMID- 21022717 TI - Penicillin treatment in surgical conditions of the chest. PMID- 21022718 TI - Some medical experiences in southwest China. PMID- 21022719 TI - The Heritage Craft school. PMID- 21022720 TI - Scratch patterns as an aid to diagnosis in three common skin conditions. PMID- 21022721 TI - MANTOUX conversion in hospital and institution staffs. PMID- 21022722 TI - Pulmonary tuberculosis; modern concept and recent advances in treatment. PMID- 21022723 TI - Recent advances in celiac disease. PMID- 21022724 TI - The trail from alchemy to pharmacology. PMID- 21022725 TI - Cancer of the small intestine. PMID- 21022726 TI - The development of a rural public health program in a tropical area, Tingo Maria, Peru. PMID- 21022727 TI - Music in the post-war therapy. PMID- 21022728 TI - Hearing aids. PMID- 21022729 TI - Further observations on the treatment of thyrotoxicosis by pancreatic extract and iodine. PMID- 21022730 TI - Functional uterine bleeding. PMID- 21022731 TI - Local and regional anaesthesia. PMID- 21022732 TI - [Not Available]. PMID- 21022733 TI - [Not Available]. PMID- 21022734 TI - [Not Available]. PMID- 21022735 TI - [Not Available]. PMID- 21022736 TI - [Not Available]. PMID- 21022737 TI - [Not Available]. PMID- 21022738 TI - [Not Available]. PMID- 21022739 TI - [Not Available]. PMID- 21022740 TI - [Not Available]. PMID- 21022742 TI - [Not Available]. PMID- 21022741 TI - [Not Available]. PMID- 21022743 TI - [Not Available]. PMID- 21022744 TI - [Not Available]. PMID- 21022745 TI - [Not Available]. PMID- 21022746 TI - Progress in inhalation therapy. PMID- 21022747 TI - [Not Available]. PMID- 21022748 TI - [Not Available]. PMID- 21022749 TI - [Not Available]. PMID- 21022750 TI - [Not Available]. PMID- 21022751 TI - The penetration of penicillin through normal and inflamed meninges. PMID- 21022752 TI - Closure of colostomies; with report of a case. PMID- 21022753 TI - A new antiseptic solution for topical application; comparative in vitro studies. PMID- 21022754 TI - Papilloma of the gall bladder. PMID- 21022755 TI - Diabetes mellitus. PMID- 21022757 TI - DANGERS of chemoprophylaxis. PMID- 21022756 TI - Carcinoma of ampulla of Vater; clinicopathological exercises. PMID- 21022758 TI - Alternating pleurisy with effusion as a manifestation of tuberculosis; a report of seven cases. PMID- 21022759 TI - Intestinal obstruction following abdominal battle wounds. PMID- 21022760 TI - Successful treatment of severe diabetic coma complicated by chronic laryngeal obstruction. PMID- 21022761 TI - Surgery of the heart and structures related to it. PMID- 21022762 TI - Actinomycosis of lungs; clinicopathological exercises. PMID- 21022763 TI - Colloid cyst of third ventricle; clinicopathological exercises. PMID- 21022764 TI - Recent developments in plastic surgery. PMID- 21022765 TI - There is hope for the victim of cerebral palsy. PMID- 21022766 TI - Disorders of the blood-forming ograns. PMID- 21022767 TI - An analysis of 200 cases of arthritis admitted to an Army general hospital. PMID- 21022768 TI - Penicillin in the treatment of Vincent's angina. PMID- 21022769 TI - The clinical diagnosis of coronary artery sclerosis. PMID- 21022770 TI - Coarctation of the aorta; a report of five cases. PMID- 21022771 TI - Pregnancy following treatment with male sex hormone in sterility due to functional bleeding. PMID- 21022772 TI - Penicillin in acute cholecystitis. PMID- 21022773 TI - Safety switch for short-wave machine. PMID- 21022774 TI - How North Carolina can reduce maternal mortality. PMID- 21022775 TI - Twinning and twins. PMID- 21022777 TI - Chronic malaria. PMID- 21022776 TI - Beta dimethylaminoethyl benzhydryl ether hydrochloride (benadryl) in the treatment of urticaria and related dermatoses. PMID- 21022778 TI - The diagnosis of early vitamin deficiency diseases. PMID- 21022779 TI - Management of enteric fistulae. PMID- 21022780 TI - Pelvic inflammatory disease and penicillin. PMID- 21022781 TI - Use the M.M.P.I. in diagnosis of psychoneuroses. PMID- 21022782 TI - Treatment of anhedonia and certain other neurologic states. PMID- 21022783 TI - Treatment of progressive muscular dystrophy with synthetic dl-a-tocopherol. PMID- 21022784 TI - Disability evaluation of the injured extremity. PMID- 21022785 TI - The treatment of metastases from carcinoma of the breast. PMID- 21022786 TI - Krukenberg tumour. PMID- 21022787 TI - Gonorrheal cervicitis and trichomonas vaginalis. PMID- 21022788 TI - [Not Available]. PMID- 21022789 TI - [Not Available]. PMID- 21022791 TI - [Not Available]. PMID- 21022790 TI - [Not Available]. PMID- 21022792 TI - [Not Available]. PMID- 21022793 TI - [Not Available]. PMID- 21022794 TI - [Not Available]. PMID- 21022795 TI - [Not Available]. PMID- 21022796 TI - [Not Available]. PMID- 21022797 TI - [Not Available]. PMID- 21022798 TI - [Not Available]. PMID- 21022799 TI - [Not Available]. PMID- 21022800 TI - [Not Available]. PMID- 21022801 TI - [Not Available]. PMID- 21022802 TI - [Not Available]. PMID- 21022803 TI - [Not Available]. PMID- 21022804 TI - [Not Available]. PMID- 21022805 TI - Ethics of medical practice; Babylon to 1945. PMID- 21022806 TI - The use of a new anti-histaminic drug (benadryl) in allergic diseases. PMID- 21022807 TI - A clarification of some difficult features in the anatomy of the soft skeleton. PMID- 21022808 TI - Management of minimal tuberculosis. PMID- 21022809 TI - The cigarette and motherhood. PMID- 21022810 TI - Burns of World War II. PMID- 21022811 TI - [Not Available]. PMID- 21022812 TI - [Not Available]. PMID- 21022813 TI - [Not Available]. PMID- 21022814 TI - [Not Available]. PMID- 21022815 TI - [Not Available]. PMID- 21022816 TI - [Not Available]. PMID- 21022817 TI - [Not Available]. PMID- 21022818 TI - [Not Available]. PMID- 21022819 TI - [Not Available]. PMID- 21022820 TI - Hypertension. PMID- 21022821 TI - Reform of medical training in the U.S.S.R. PMID- 21022822 TI - Prof. Dr. Alfred Vogt, 1879-1943 [biography; bibliography]. PMID- 21022823 TI - [Not Available]. PMID- 21022824 TI - [Not Available]. PMID- 21022825 TI - [Not Available]. PMID- 21022826 TI - [Not Available]. PMID- 21022827 TI - [Not Available]. PMID- 21022828 TI - [Not Available]. PMID- 21022829 TI - [Not Available]. PMID- 21022830 TI - [Not Available]. PMID- 21022831 TI - [Not Available]. PMID- 21022832 TI - [Not Available]. PMID- 21022833 TI - [Not Available]. PMID- 21022834 TI - [Not Available]. PMID- 21022835 TI - [Not Available]. PMID- 21022836 TI - [Not Available]. PMID- 21022837 TI - [Not Available]. PMID- 21022838 TI - [Not Available]. PMID- 21022839 TI - [Not Available]. PMID- 21022840 TI - [Not Available]. PMID- 21022841 TI - [Not Available]. PMID- 21022842 TI - [Not Available]. PMID- 21022843 TI - [Not Available]. PMID- 21022844 TI - [Not Available]. PMID- 21022845 TI - [Not Available]. PMID- 21022846 TI - [Not Available]. PMID- 21022847 TI - [Not Available]. PMID- 21022848 TI - [Not Available]. PMID- 21022850 TI - [Not Available]. PMID- 21022849 TI - [Not Available]. PMID- 21022851 TI - [Not Available]. PMID- 21022852 TI - [Not Available]. PMID- 21022853 TI - [Not Available]. PMID- 21022854 TI - The future of the Texas Medical Center. PMID- 21022855 TI - Hay fever; fact and fiction. PMID- 21022856 TI - Field practice in preventive medicine for medical students. PMID- 21022857 TI - Insect repellents. PMID- 21022858 TI - Chemical destruction of circumscribed areas of the central nervous system. PMID- 21022859 TI - The use of d-desoxyephedrine in neuropsychiatry. PMID- 21022860 TI - The production of neuro-hypertension by the kidney. PMID- 21022861 TI - Some observations on the effects of a mixture of high molecular alkyl-dimethyl benzyl ammonium chlorides on various invertebrates. PMID- 21022862 TI - The distribution of species of sandflies, genus Phlebotomus, in the United States and their relation to the transmission of leishmaniasis. PMID- 21022863 TI - The contact splint. PMID- 21022864 TI - The organization of a hospital blood bank. PMID- 21022865 TI - Sulfasuxidine and sulfathalidine. PMID- 21022866 TI - [Not Available]. PMID- 21022867 TI - [Not Available]. PMID- 21022868 TI - [Not Available]. PMID- 21022870 TI - [Not Available]. PMID- 21022869 TI - Anaemia in pregnancy. PMID- 21022871 TI - DISCOVERY of tuberculosis at separation centers. PMID- 21022872 TI - PROGRESS in the care of paraplegics. PMID- 21022873 TI - NEW type of foot drop brace. PMID- 21022874 TI - INFLUENZA antibody studies. PMID- 21022875 TI - VITAMIN concentrates. PMID- 21022876 TI - NEW DDT applicators for screens. PMID- 21022877 TI - FIRST Army regulation on industrial medicine. PMID- 21022878 TI - DISTRIBUTING center for parasitological specimens. PMID- 21022879 TI - PETROFF needle for large-scale blood collections. PMID- 21022880 TI - DENTISTRY in a Jap prison camp. PMID- 21022881 TI - JEEP aerosol generator for DDT applications. PMID- 21022882 TI - HEMOLYTIC Corynebacterium resembling C. ovis and C. pyogenes in man. PMID- 21022883 TI - ADVANCEMENT of psychiatry. PMID- 21022884 TI - STREPTOMYCIN. PMID- 21022885 TI - GLYCOL vapors in air disinfection. PMID- 21022886 TI - Epidemics. PMID- 21022887 TI - Fractures of the feet and toes. PMID- 21022888 TI - Evaluation of penetrating spinal wounds. PMID- 21022889 TI - Diphtheria epidemic in adults in the tropics. PMID- 21022890 TI - Hysterical flexion deformity of the vertebral column; camptocormia. PMID- 21022891 TI - Conservation and preventive maintenance. PMID- 21022892 TI - War wounds of the liver. PMID- 21022893 TI - A program of definitive psychiatry at army level. PMID- 21022894 TI - An unusual case of mumps without parotitis. PMID- 21022895 TI - The administration of fixed hospital laboratories. PMID- 21022896 TI - A micro method for determination of hemoglobin. PMID- 21022897 TI - Modification of a standard chlorine comparator for field ortho-tolidine-arsenite (OTA) tests. PMID- 21022898 TI - Medical aspects of blast. PMID- 21022899 TI - Pinta-like lesions among natives of Guam. PMID- 21022900 TI - Impressions of a POW medical officer in Japanese concentration camps. PMID- 21022901 TI - Segregated training for recruits with minor orthopedic disabilities and complaints. PMID- 21022902 TI - The psychotic naval prisoner. PMID- 21022903 TI - The mental defective and the under-age man in the Navy. PMID- 21022904 TI - Method for practicing preventive psychiatry in a naval personnel separation center. PMID- 21022905 TI - Shigellosis studies; resistance of Shigella flexneri III to therapy with sulfadiazine. PMID- 21022907 TI - Traumatic rupture of adductor muscles of the thigh. PMID- 21022906 TI - FAILURE of type specific Streptococcus pyogenes vaccine to prevent respiratory infections. PMID- 21022908 TI - Traumatic ossifying myositis. PMID- 21022909 TI - 1,265 pneumonia cases with no deaths. PMID- 21022910 TI - Effect of blood donations on blood pressure of hypertensives. PMID- 21022911 TI - Intravenous administration of morphine tartrate. PMID- 21022912 TI - Unusual conditions aggravated by seasickness; report of two cases. PMID- 21022913 TI - Cutaneous diphtheria. PMID- 21022914 TI - Penicillin reaction. PMID- 21022915 TI - Fulminating septicemia due to Staphylococcus epidermidis; report of a case with autopsy findings. PMID- 21022916 TI - Meningococcal conjunctivitis. PMID- 21022918 TI - Irrigation apparatus for resections. PMID- 21022917 TI - Method for producing soapy solution in whirlpool tank. PMID- 21022919 TI - A simple type of immersion sterilizer. PMID- 21022920 TI - Earth motion from the atomic bomb test. PMID- 21022921 TI - Science and a national policy. PMID- 21022922 TI - Scientific method and human values. PMID- 21022924 TI - The aim and progress of psychology. PMID- 21022923 TI - The meaning of evolution. PMID- 21022925 TI - Tetraploidy in flax. PMID- 21022926 TI - Production and properties of 2,3-butanediol; the effects of surface-volume ratio and reduced pressure on the fermentation of carbohydrates by Aerobacillus polymyxa and Aerobacter aerogenes. PMID- 21022927 TI - Dried milk powder; the photolysis of riboflavin in milk powders. PMID- 21022928 TI - The thiamin content of meat. PMID- 21022930 TI - [Not Available]. PMID- 21022929 TI - [Not Available]. PMID- 21022931 TI - [Not Available]. PMID- 21022932 TI - [Not Available]. PMID- 21022933 TI - [Not Available]. PMID- 21022934 TI - [Not Available]. PMID- 21022935 TI - [Not Available]. PMID- 21022936 TI - [Not Available]. PMID- 21022937 TI - [Not Available]. PMID- 21022939 TI - [Not Available]. PMID- 21022938 TI - [Not Available]. PMID- 21022940 TI - Heat capacity of a two-phase system, with applications to vapor corrections in calorimetry. PMID- 21022941 TI - Cell size in Amphiuma. PMID- 21022942 TI - Water level relationships of plants in the Tennessee Valley with particular reference to malaria control. PMID- 21022943 TI - The effect of x-rays on the ovaries and estrous cycle of the golden hamster (Cricetus auratus Waterhouse). PMID- 21022944 TI - The conditions of equilibrium of non-stoichiometric chemical compounds. PMID- 21022945 TI - The helium content of atmospheric air. PMID- 21022947 TI - The structure and reactivity of the halogenobenzenes. PMID- 21022946 TI - A micro-analysis of the helium and neon contents of air. PMID- 21022948 TI - Meteorology of the lower stratosphere. PMID- 21022949 TI - Ozone. PMID- 21022950 TI - The absorption spectrum of acetaldehyde in the vacuum ultra-violet. PMID- 21022951 TI - The thermal decomposition of hydrogen peroxide vapour. PMID- 21022952 TI - Hopes and hurdles in the cancer problem. PMID- 21022953 TI - Science and society. PMID- 21022954 TI - The strange trinity called man. PMID- 21022955 TI - The parental devotion of birds. PMID- 21022956 TI - Compression distillation. PMID- 21022957 TI - War on weeds. PMID- 21022958 TI - Use of 2,4-dichlorophenoxyacetic acid as a selective herbicide in the tropics. PMID- 21022959 TI - Control of ragweed pollen production with 2,4-dichlorophenoxyacetic acid. PMID- 21022960 TI - Rapid estimation of the phytocidal action of chemicals. PMID- 21022961 TI - Treatment of muck and manure with 2,4-dichlorophenoxyacetic acid to inhibit germination of weed seeds. PMID- 21022962 TI - Herbicidal action of 2,4-dichlorophenoxyacetic acid on the water hyacinth, Eichornia crassipes. PMID- 21022963 TI - Inhibition of fungus respiration; a metabolic bio-assay method. PMID- 21022964 TI - Mellon Institute; its organization and management. PMID- 21022965 TI - The contribution of Kansas to American Men of Science, 7th edition. PMID- 21022966 TI - An analysis of scatter in intelligence test results. PMID- 21022967 TI - Observations on abnormal anatomy of a two-headed calf. PMID- 21022968 TI - Triangles in the teeth of the mammalian genus Ondatra. PMID- 21022969 TI - The parent's role in resident treatment. PMID- 21022970 TI - Can social work help the sex delinquent? PMID- 21022971 TI - The responsibility of psychiatry. [Discussion]. PMID- 21022972 TI - Nightmares and the combat neuroses. PMID- 21022973 TI - Christmas in American culture. PMID- 21022974 TI - A proposed projective attitude test. PMID- 21022975 TI - Anti-feminism and race prejudice. PMID- 21022977 TI - The epileptic patient and the nurse. PMID- 21022976 TI - The factor of maturity in officer selection. PMID- 21022978 TI - The newly deafened patient. PMID- 21022979 TI - Who said lice? PMID- 21022980 TI - Nurses and their professional organizations. PMID- 21022981 TI - The industrial nurse and mental hygiene. PMID- 21022982 TI - The aphasic patient. PMID- 21022983 TI - A new and safe method of gastric suction. PMID- 21022984 TI - The stimulation and maintenance of lactation. PMID- 21022985 TI - Orthopedic surgery in the reconstruction of hands. PMID- 21022986 TI - Filing hospital medical records. PMID- 21022987 TI - Club feet correction. PMID- 21022988 TI - A noiseless tonsillectomy morning. PMID- 21022989 TI - The physical examination program; the industrial nurse's role. PMID- 21022990 TI - Rehabilitation of the handicapped; the role of the industrial nurse. PMID- 21022991 TI - Health resources for the nurse in industry; Federal, State and local agencies. PMID- 21022992 TI - The South Pacific nursing service. PMID- 21022993 TI - The physiotherapists' part in the science of physical rehabilitation. PMID- 21022994 TI - Acute ascending paralysis and myelitis. PMID- 21022995 TI - The organisation of the nursing profession. PMID- 21022996 TI - Clinical features and nursing care of the pneumonias. PMID- 21022998 TI - Post-war opportunities for male nurses. PMID- 21022997 TI - Hormones in human reproduction; testosterone. PMID- 21022999 TI - CARE of the criminally insane. PMID- 21023000 TI - Sex hormones in human reproduction; oestrin deprivation theory in menstruation. PMID- 21023001 TI - Case of severe malnutrition. PMID- 21023002 TI - Some drugs in modern use; insulin. PMID- 21023003 TI - Aural diseases in infancy. PMID- 21023004 TI - Physiology of labour. PMID- 21023005 TI - Otitis externa. PMID- 21023006 TI - Care of the old and infirm in industry. PMID- 21023007 TI - Physiology underlying the treatment of post-partum haemorrhage. PMID- 21023008 TI - Leprosy service in the colonies. PMID- 21023009 TI - STATE national health service; general considerations and the nurse's place in it. PMID- 21023010 TI - GOVERNMENT scheme for a national health service; details of bill now before Parliament. PMID- 21023011 TI - Treatment and recovery of a case of anxiety state. PMID- 21023012 TI - Behaviour of foetus in utero. PMID- 21023014 TI - A few cases of ruptured intervertebral discs from an orthopaedist's log book. PMID- 21023013 TI - Predecessors of penicillin; superstitions and strange ingredients. PMID- 21023015 TI - Pre- and post-operative care of a patient with a ruptured intervertebral disc. PMID- 21023016 TI - EVERY face tells the nurse a story. PMID- 21023017 TI - SUMMARY of the conclusions and recommendations of the Sub-committee on Mental Nursing and the Nursing of the Mentally Defective. PMID- 21023018 TI - A typical case of advanced tabes dorsalis. PMID- 21023019 TI - The management of the neurosurgical patient. PMID- 21023020 TI - Typhus fever. PMID- 21023021 TI - Some physical methods of treating mental disorders. PMID- 21023022 TI - Ammonia burns to the eyes. PMID- 21023023 TI - NURSES and national insurance. PMID- 21023024 TI - Nurses and rehabilitation. PMID- 21023025 TI - Nursing in Czechoslovakia. PMID- 21023027 TI - The uses of infra-red radiation for spastic paraplegia. PMID- 21023026 TI - The Dawn Society and corneal transplantation; a new technique practised in the Soviet Union and the United States. PMID- 21023028 TI - B.C.G.: a general survey. PMID- 21023030 TI - The rehabilitation of the tuberculous nurse. PMID- 21023029 TI - Tuberculosis home contacts; a technique of routine examination at Ealing Chest Clinic. PMID- 21023031 TI - Neurotic illness in children. PMID- 21023032 TI - Flat feet. PMID- 21023033 TI - Psychiatric nurse. PMID- 21023034 TI - The art and profession of nursing. PMID- 21023035 TI - The modern approach to dental decay. PMID- 21023037 TI - Fresh vistas and new trends in education. PMID- 21023036 TI - Electro therapy. PMID- 21023038 TI - Physiotherapy in the after-care of burn injuries. PMID- 21023039 TI - Galvanic current; Faradic current; sinusoidal current; high frequency current; and the electrical treatment of paralysis. PMID- 21023040 TI - Nutrition lessons from the war. PMID- 21023041 TI - Spinal deformities. PMID- 21023042 TI - PHYSIOTHERAPY corrects and cures; an early beginning and patient carrying out of treatments and exercises help these children to grow up straight. PMID- 21023043 TI - Public health nursing in relation to illness. PMID- 21023044 TI - Public health nursing salaries, 1945. PMID- 21023045 TI - Visiting nurse society and cancer patient. PMID- 21023046 TI - Public health nurse in the cancer program. PMID- 21023047 TI - Prostitution, promiscuity, venereal disease. PMID- 21023049 TI - OPPORTUNITIES for teaching eye health. PMID- 21023048 TI - Health education in a housing project. PMID- 21023050 TI - [Not Available]. PMID- 21023051 TI - [Not Available]. PMID- 21023052 TI - [Not Available]. PMID- 21023053 TI - Chronic disease challenges the profession. PMID- 21023054 TI - Brain surgery performed under shell fire. PMID- 21023055 TI - The Rh factor influences infant anemia. PMID- 21023056 TI - The hospital nurse speaks up. PMID- 21023057 TI - The treatment of injuries. PMID- 21023058 TI - The male nurse in China proves valuable. PMID- 21023059 TI - Tampons as menstrual guards. PMID- 21023060 TI - Chronics need skillfull nursing. PMID- 21023061 TI - Hospital personnel shortage. PMID- 21023062 TI - Flight nurses make contribution to industry. PMID- 21023063 TI - Mission to Nagasaki. PMID- 21023064 TI - A new theory for the control of accommodation. PMID- 21023065 TI - Changes in power and axis of cylindrical errors after convergence. PMID- 21023066 TI - Reduction of reflections. PMID- 21023067 TI - The physical and chemical properties of plastic contact lenses. PMID- 21023068 TI - On primary glaucoma. PMID- 21023069 TI - Ultra-violet; a new health guard for the refracting room. PMID- 21023070 TI - The case system in terminal optometry. PMID- 21023071 TI - Epidemic kerato-conjunctivitis associated with skin lesions. PMID- 21023072 TI - The use of crystalline penicillin in corneal and intraocular infection. PMID- 21023073 TI - An operation for posterior route extraction of intraocular foreign bodies. PMID- 21023074 TI - The treatment of trachoma. PMID- 21023075 TI - Schistosomiasis of the conjunctiva. PMID- 21023076 TI - A case of secondary oblique facial cleft. PMID- 21023077 TI - The relation of corneal vascularisation and conjunctival transparency to general diseases. PMID- 21023078 TI - Ocular decompensation. PMID- 21023079 TI - Notes on oncocerciasis in Guatemala. PMID- 21023080 TI - Lachesine, a new mydriatic. PMID- 21023081 TI - Lateral orbitotomy (Kronlein's operation). PMID- 21023082 TI - The measurement of ultraviolet radiation useful in heliotherapy. PMID- 21023083 TI - Visual critical flicker frequency as a function of intensity. PMID- 21023084 TI - Brightness discrimination and visual acuity as functions of intensity. PMID- 21023086 TI - The aging of glass surfaces. PMID- 21023085 TI - The effect of quality of illumination on the results of the Ishihara test. PMID- 21023087 TI - A combination arc-spark source for magnesium analysis. PMID- 21023088 TI - On the primary chromatic coefficients of a lens system. PMID- 21023089 TI - Measurement of the radius of curvature of concave spheres. PMID- 21023090 TI - On the basic sensation curves of the three-color theory. PMID- 21023091 TI - Spectrophotometric and colorimetric determination of the colors of the TCCA standard color cards. PMID- 21023092 TI - A lens to supplant the spectrograph slit. PMID- 21023093 TI - A photoelectric spectrophotometer for the Schumann region. PMID- 21023094 TI - Correction of imperfect week cylindrical lenses. PMID- 21023095 TI - Experiments on the use of infrared sensitive phosphors in photography of the spectrum. PMID- 21023096 TI - Spectral intensity measurements with photo-tubes and the oscillograph. PMID- 21023097 TI - Spectrochemical analysis with the oscillograph. PMID- 21023098 TI - Transmittance and reflectance of germicidal (lambda 2537) energy. PMID- 21023099 TI - A device to facilitate the reading of spectrophotometric curves. PMID- 21023100 TI - Correcting the spherical and chromatic aberrations of the eye. PMID- 21023101 TI - Resonance spectrum of iodine. PMID- 21023103 TI - Cases indicating contact lenses. PMID- 21023102 TI - An approach to the myopia reduction problem. PMID- 21023104 TI - Thoughts on the myopia control controversy. PMID- 21023105 TI - BRITISH views on contact lens fitting. PMID- 21023106 TI - A modification of the ptosis crutch. PMID- 21023107 TI - Patent problems and the functioning of the American Patent System. PMID- 21023108 TI - Plastics in the manufacture of contact lenses. PMID- 21023109 TI - Visual discomfort and fluorescent light. PMID- 21023110 TI - Sight development. PMID- 21023111 TI - Visual survey of school children. PMID- 21023112 TI - The Oregon plan. PMID- 21023113 TI - BRAILLE programs for the blind. PMID- 21023114 TI - Training the British Empire's war-blinded in India. PMID- 21023115 TI - Suggestions for a vocational guidance program in schools for the blind. PMID- 21023116 TI - Eye clinic in the Arctic. PMID- 21023117 TI - The relationship of dental malocclusion to vacuum-otitis media and the use of dental splints during descent from altitudes. PMID- 21023118 TI - Dental treatment for the prevention of aerotitis media. PMID- 21023119 TI - Deep infections of the neck with particular reference to the role of dental foci. PMID- 21023120 TI - Suppurative labyrinthitis. PMID- 21023121 TI - Secretory otitis media. PMID- 21023122 TI - War deafness in gunnery instructors. PMID- 21023123 TI - Psychogenic deafness. PMID- 21023124 TI - Penicillin therapy in external otitis. PMID- 21023125 TI - Otolaryngology in the European Theater of World War II. PMID- 21023126 TI - An otolaryngologist's experience in World War II. PMID- 21023127 TI - Progress in otolaryngology since 1937; an appraisal of the present status of Dr. Mosher's Unsolved problems. PMID- 21023128 TI - Status asthmaticus. PMID- 21023129 TI - Oropharyngeal manifestations of erythema multiforme. PMID- 21023130 TI - The site of the facial nerve lesion in cases of Ramsay Hunt's syndrome. PMID- 21023131 TI - Follicular odontoma of the maxillary sinus. PMID- 21023132 TI - A case of osteomyelitis of the frontal bone extending from the frontal sinus, complicated by meningitis; recovery. PMID- 21023133 TI - Bilateral granuloma of the larynx following intratracheal anesthesia. PMID- 21023134 TI - Hairy or black tongue. PMID- 21023135 TI - Fibrolipoma of the face; report of a case. PMID- 21023136 TI - Two unusual esophageal cases. PMID- 21023137 TI - Tympanosympathectomy; a surgical technic for the relief of tinnitus aurium. PMID- 21023138 TI - Otitis externa; clinical observations and microbiologic flora. PMID- 21023139 TI - A study of chronic suppurative otitis media at the Pennsylvania School for the Deaf. PMID- 21023140 TI - A study of the attitudinal reflexes of Magnus and de Kleijn in thalamic man. PMID- 21023141 TI - Planning the rhinoplasty. PMID- 21023142 TI - A review of 100 cases of acute aero-otitis. PMID- 21023143 TI - Treatment of complicated acute sinusitis with penicillin. PMID- 21023144 TI - Some facts about stuttering. PMID- 21023145 TI - The relationship between voluntary non-fluency and stuttering. PMID- 21023146 TI - Cluttering. PMID- 21023147 TI - Sigmatismus nasalis. PMID- 21023148 TI - A review of the available literature on the larynx and laryngeal surgery for 1945. PMID- 21023149 TI - The selection of hearing aids. PMID- 21023150 TI - Frontal sinusitis. PMID- 21023151 TI - Federal aid to the hearing handicapped. PMID- 21023152 TI - Acceleration of healing by pressure application to experimental thermal burns. PMID- 21023153 TI - Haemolysin tests for the rapid identification of Cl. oedematiens and Cl. septicum. PMID- 21023154 TI - Notes on the Weil-Felix reaction in typhus fever and other diseases. PMID- 21023155 TI - The isolation of organisms of the pleuropneumonia group from the genital tract of men and women. PMID- 21023156 TI - The influence of surface-active substances on the growth of acid-fast bacteria. PMID- 21023157 TI - Neutralisation of C. diphtheriae type toxins with standard antitoxin, as determined by skin reactions in guinea-pigs. PMID- 21023158 TI - A histological and bacteriological study of healing burns with an enquiry into the significance of local infection. PMID- 21023159 TI - An experimental study of the healing of wounds, with special reference to the action of heart extract powder (Doljanski). PMID- 21023160 TI - The diffusion of antiseptics through agar gels, with special reference to the agar cup assay method of estimating the activity of penicillin. PMID- 21023161 TI - Platymeria. PMID- 21023162 TI - Stimulation of the growth of mycobacteria by egg yolk. PMID- 21023163 TI - The demonstration of certain fatty substances in paraffin sections. PMID- 21023164 TI - A case of multiple tuberculomata of the liver. PMID- 21023165 TI - A new species of Shigella. PMID- 21023166 TI - An institutional outbreak of diarrhoea due to a hitherto undescribed dysentery bacillus. PMID- 21023167 TI - A case of islet-cell tumour of pancreas. PMID- 21023168 TI - Susceptibility of the golden hamster (Cricetus auratus) to Mycobacterium tuberculosis hominis and bovis. PMID- 21023169 TI - The effects of (a) freeze-drying and (b) low temperature on the viability of Mycobacterium tuberculosis. PMID- 21023170 TI - An improved method for the histological examination of sternal puncture material. PMID- 21023171 TI - Cough; difficult breathing; swelling of face and neck. PMID- 21023172 TI - Receding chin; difficult breathing. PMID- 21023173 TI - Labored breathing. PMID- 21023175 TI - Research for the partially seeing. PMID- 21023174 TI - Educational reconditioning in Army general hospitals. PMID- 21023176 TI - Child guidance clinic as a community project. PMID- 21023177 TI - California's program for children with cerebral palsy. PMID- 21023178 TI - Isolation of St. Louis encephalitis virus from the peripheral blood of a human subject. PMID- 21023179 TI - Further observations of epidemic diarrhea of the newborn; observation of a biphasic type of clinical course; therapeutic measures including prophylactic and therapeutic use of gamma globulin. PMID- 21023180 TI - A study of premature infants observed in a private hospital before and after the establishment of a premature nursery. PMID- 21023181 TI - Salmonella choleraesuis (variety Kunzendorf) bacteriemia complicating streptococcal sore throat. PMID- 21023183 TI - Ratbite fever. PMID- 21023182 TI - Preliminary observations on some children with rheumatic heart disease transported to a subtropical climate. PMID- 21023184 TI - The preparation and use of concentrated red blood cell transfusions in infancy. PMID- 21023185 TI - An evaluation of the distinction in the clinical course and the treatment of erythroblastosis and icterus gravis. PMID- 21023186 TI - The use of Rh-positive blood cells in the treatment of erythroblastosis fetalis. PMID- 21023187 TI - Appraisal of treatment of Hemophilus influenzae type B meningitis with specific rabbit serum and sulfonamides; based on observation of 60 cases. PMID- 21023188 TI - Auricular fibrillation in infancy; report of a case with fleeting paroxysms. PMID- 21023189 TI - Extreme paroxysmal supraventricular tachycardia; case report. PMID- 21023190 TI - Coronary thrombosis; report of a case in an infant eleven months of age. PMID- 21023191 TI - Pneumococcic stomatitis. PMID- 21023193 TI - Leptomeningeal cyst associated with hemiplegia and skull defect of traumatic origin. PMID- 21023192 TI - Right-sided transient paralysis of the diaphragm in a newborn infant. PMID- 21023194 TI - Bismuth nephrosis with anuria in an infant; report of a case. PMID- 21023195 TI - Vertebral hemangioma in children. PMID- 21023196 TI - The system of medical care of children in Sweden. PMID- 21023197 TI - Tuberculosis as a school problem. PMID- 21023198 TI - The prevention of tuberculosis in the Los Angeles city schools. PMID- 21023199 TI - School health service. PMID- 21023200 TI - HEALTH implications of the physical education program. PMID- 21023201 TI - [Not Available]. PMID- 21023202 TI - [Not Available]. PMID- 21023203 TI - [Not Available]. PMID- 21023204 TI - [Not Available]. PMID- 21023205 TI - [Not Available]. PMID- 21023206 TI - [Not Available]. PMID- 21023207 TI - [Not Available]. PMID- 21023208 TI - [Not Available]. PMID- 21023209 TI - [Not Available]. PMID- 21023210 TI - [Not Available]. PMID- 21023211 TI - [Not Available]. PMID- 21023212 TI - [Not Available]. PMID- 21023213 TI - [Not Available]. PMID- 21023215 TI - [Not Available]. PMID- 21023214 TI - [Not Available]. PMID- 21023216 TI - [Not Available]. PMID- 21023217 TI - [Not Available]. PMID- 21023218 TI - [Not Available]. PMID- 21023219 TI - [Not Available]. PMID- 21023220 TI - [Not Available]. PMID- 21023221 TI - [Not Available]. PMID- 21023222 TI - [Not Available]. PMID- 21023223 TI - [Not Available]. PMID- 21023224 TI - How parents hinder adolescents' adjustments to the opposite sex. PMID- 21023225 TI - Mental hygiene for children and youth. PMID- 21023226 TI - TERPIN hydrate. PMID- 21023227 TI - TURPENTINE oil. PMID- 21023228 TI - Optical crystallographic constants for N.F. VIII. PMID- 21023229 TI - The assay of papain, with suggestions for the modification of the tentatively accepted assay. PMID- 21023230 TI - A study of the identification test for sesame oil N.F. PMID- 21023231 TI - The use of acetarsone, carbarsone, and iodochlorohydroxyquinoline. PMID- 21023234 TI - Diabetic specialties. PMID- 21023233 TI - IODOCHLOROHYDROXYQUINOLINE. PMID- 21023232 TI - CARBARSONE. PMID- 21023235 TI - ESTROGENS. PMID- 21023236 TI - PACKAGING and selling. PMID- 21023237 TI - [Not Available]. PMID- 21023238 TI - [Not Available]. PMID- 21023239 TI - [Not Available]. PMID- 21023241 TI - [Not Available]. PMID- 21023240 TI - DDT. PMID- 21023242 TI - [Not Available]. PMID- 21023243 TI - [Not Available]. PMID- 21023244 TI - [Not Available]. PMID- 21023245 TI - [Not Available]. PMID- 21023246 TI - [Not Available]. PMID- 21023247 TI - [Not Available]. PMID- 21023248 TI - [Not Available]. PMID- 21023249 TI - [Not Available]. PMID- 21023250 TI - [Not Available]. PMID- 21023252 TI - [Not Available]. PMID- 21023251 TI - [Not Available]. PMID- 21023253 TI - [Not Available]. PMID- 21023254 TI - [Not Available]. PMID- 21023255 TI - [Not Available]. PMID- 21023256 TI - [Not Available]. PMID- 21023257 TI - Formulation of the antibiotics. PMID- 21023258 TI - Trichinosis. PMID- 21023259 TI - [Not Available]. PMID- 21023260 TI - [Not Available]. PMID- 21023261 TI - [Not Available]. PMID- 21023262 TI - [Not Available]. PMID- 21023263 TI - Studies of modern synthetic emulgents; the effect of electrolytes in emulsions and creams. PMID- 21023264 TI - Application of the theory of adsorption to oil bleaching. PMID- 21023265 TI - The vitamin B complex. PMID- 21023266 TI - Detection of para-hydroxybenzoic acid. PMID- 21023267 TI - Bile and bile salt preparations. PMID- 21023268 TI - The use of silver salts in the study of nerve tissue. PMID- 21023269 TI - [Not Available]. PMID- 21023270 TI - [Not Available]. PMID- 21023271 TI - [Not Available]. PMID- 21023272 TI - [Not Available]. PMID- 21023273 TI - [Not Available]. PMID- 21023274 TI - [Not Available]. PMID- 21023275 TI - [Not Available]. PMID- 21023276 TI - The present status of oral and nasal cold vaccines. PMID- 21023277 TI - [Not Available]. PMID- 21023278 TI - [Not Available]. PMID- 21023279 TI - [Not Available]. PMID- 21023281 TI - [Not Available]. PMID- 21023280 TI - [Not Available]. PMID- 21023282 TI - [Not Available]. PMID- 21023283 TI - DRUG therapy and diagnosis of neurologic disorders. PMID- 21023284 TI - INFERTILITY: incidence and diagnosis. PMID- 21023286 TI - [Not Available]. PMID- 21023285 TI - [Not Available]. PMID- 21023287 TI - [Not Available]. PMID- 21023288 TI - PENICILLIN by inhalation; strong nebulized solution effective in upper respiratory tract infections. PMID- 21023289 TI - An in vivo study of the pH of synovial fluid in dogs. PMID- 21023290 TI - Effect of concussion upon the polarizability of the brain. PMID- 21023291 TI - The peripheral visual acuity of 100 subjects under scotopic conditions. PMID- 21023292 TI - Influence of blood sugar levels on resistance to low oxygen tension in the cat. PMID- 21023293 TI - Effects of high acceleratory forces and their alleviation. PMID- 21023294 TI - The effect of different concentrations of nicotinic acid amide on the work output of perfused frog muscles. PMID- 21023295 TI - Diamine oxidase (histaminase) activity of kidney and other organs in the hypersensitive state. PMID- 21023296 TI - The cardiovascular responses to the breathing of 100 per cent oxygen at normal barometric pressure. PMID- 21023297 TI - The tolerance of man to cold as affected by dietary modifications; proteins versus carbohydrates, and the effect of variable protective clothing. PMID- 21023298 TI - The tolerance of man to cold as affected by dietary modification; carbohydrate versus fat and the effect of the frequency of meals. PMID- 21023299 TI - Inhibition of the erythema of sunburn by large doses of ultraviolet radiation. PMID- 21023300 TI - The erythemal threshold for sunburn. PMID- 21023301 TI - Evaluation of protective measures against sunburn. PMID- 21023302 TI - Capillary permeability; perfusion of frog and guinea pig hind limbs. PMID- 21023303 TI - Adrenal function following ovariectomy in the rat. PMID- 21023304 TI - The inactivation of placental toxin by human serum. PMID- 21023305 TI - Renal tubular reabsorption, metabolic utilization and isomeric fractionation of lactic acid in the dog. PMID- 21023307 TI - Spontaneous experiences reported by a group of experimental subjects. PMID- 21023306 TI - Personality of the problem child. PMID- 21023308 TI - The theory of psychomotion as applied to a study of temperament. PMID- 21023309 TI - The non-correction method and the delayed response problem of Blodgett and McCutchan. PMID- 21023310 TI - Can chimpanzees become morphine addicts? PMID- 21023311 TI - Estrous behavior and hormones in the cow. PMID- 21023312 TI - Response errors in conditioned discrimination; preliminary studies in non adjustive behavior. PMID- 21023313 TI - Psychology in world reconstruction. PMID- 21023314 TI - Cultural aspects of women's vocational problems in post World War II. PMID- 21023315 TI - Child psychology and societal reconstruction. PMID- 21023317 TI - Radio and international co-operation as a problem for psychological research. PMID- 21023316 TI - Polling postwar issues. PMID- 21023318 TI - Psychology in the emerging education. PMID- 21023319 TI - In-service training for institutional employees. PMID- 21023320 TI - The Pavlovian theory of generalization. PMID- 21023321 TI - Emotion in man and animal; an analysis of the intuitive processes of recognition. PMID- 21023322 TI - Psychological testing in military clinical psychology; personality testing. PMID- 21023323 TI - Personalistic psychology as science; a reply. PMID- 21023324 TI - The outlook for mosquito-borne disease control in California. PMID- 21023325 TI - Community education in health. PMID- 21023327 TI - We can eliminate scabies. PMID- 21023326 TI - Some problems of dental health education. PMID- 21023328 TI - Why pollute the atmosphere? PMID- 21023329 TI - Social factors and mental health; early childhood. PMID- 21023330 TI - Health education in a county. PMID- 21023331 TI - Causes of promiscuity. PMID- 21023332 TI - What is health? PMID- 21023333 TI - Visual aids in health education. PMID- 21023334 TI - Educating the emotions. PMID- 21023335 TI - Cancer of the breast; its diagnosis and treatment. PMID- 21023336 TI - Some aspects of the public responsibility for child health. PMID- 21023337 TI - Diabetes in childhood. PMID- 21023339 TI - Diphtheria. PMID- 21023338 TI - Some domestic uses of D.D.T. PMID- 21023341 TI - Pasteurisation in the Province of Quebec; with special reference to Montreal. PMID- 21023340 TI - Famine conditions and epidemic risks. PMID- 21023342 TI - Mental deficiency in the past. PMID- 21023343 TI - Lines of approach to public health. PMID- 21023344 TI - Allergic shock following administration of anti-diphtheritic serum. PMID- 21023345 TI - An outbreak of Sonne dysentery. PMID- 21023346 TI - HYGIENE in the schools; and the school health service. PMID- 21023347 TI - Milk, food and drug control. PMID- 21023348 TI - Tuberculosis control. PMID- 21023349 TI - Public health nursing. PMID- 21023350 TI - Communicable disease control and sanitation. PMID- 21023352 TI - [Not Available]. PMID- 21023351 TI - [Not Available]. PMID- 21023353 TI - [Not Available]. PMID- 21023354 TI - [Not Available]. PMID- 21023355 TI - [Not Available]. PMID- 21023356 TI - [Not Available]. PMID- 21023357 TI - [Not Available]. PMID- 21023358 TI - [Not Available]. PMID- 21023359 TI - [Not Available]. PMID- 21023360 TI - [Not Available]. PMID- 21023361 TI - Treatment of acute arrhythmias during anesthesia by intravenous procaine. PMID- 21023362 TI - A blood transfusion service; dangers and safeguards. PMID- 21023363 TI - The frontiers of anesthesia. PMID- 21023364 TI - Statistical systems in anesthesiology. PMID- 21023365 TI - Repeated sympathetic blocks; their limitation and value. PMID- 21023366 TI - On the pressor activity and stability of different mixtures of ephedrine and pituitary (posterior lobe) extract. PMID- 21023368 TI - A new laryngoscope for intubation of infants. PMID- 21023367 TI - A new lethal dose of curare, with some observations on the pathology produced by large doses. PMID- 21023370 TI - BIBLIOGRAPHY of war medicine and surgery. PMID- 21023369 TI - A method of administering ether-air by continuous insufflation. PMID- 21023371 TI - [Not Available]. PMID- 21023372 TI - [Not Available]. PMID- 21023373 TI - [Not Available]. PMID- 21023374 TI - Urinary amoebiasis; a critical review. PMID- 21023375 TI - Malaria epidemics at exceptionally high altitudes in Kenya. PMID- 21023376 TI - Tropical ophthalmology. PMID- 21023377 TI - Heterogeneity of strains of polymorphic trypanosomes; its relation to natural and experimental transmission. PMID- 21023378 TI - Malaria. PMID- 21023379 TI - Standardization of photofluorographic equipment. PMID- 21023380 TI - Apical localization of phthisis; its significance in treatment by prolonged rest in bed. PMID- 21023382 TI - Surgery in the tuberculous patient with amyloidosis. PMID- 21023381 TI - Pulmonary function tests; a discussion of ventilatory tests; a description of a method for measuring the diffusion of oxygen and carbon dioxide in the lungs. PMID- 21023383 TI - Hycodan; dihydrocodeinone. PMID- 21023384 TI - Depth growth of acid-fast bacilli in liquid media. PMID- 21023385 TI - Diaminodiphenylsulfone derivatives; the therapeutic effects of two new derivatives in experimental tuberculosis. PMID- 21023386 TI - Effect of human gastric juice on tubercle bacilli; with special reference to the diagnosis of active pulmonary tuberculosis. PMID- 21023387 TI - Anatomical studies on human tuberculosis; primary foci without lymph node changes; additional observations. PMID- 21023388 TI - [Not Available]. PMID- 21023389 TI - [Not Available]. PMID- 21023390 TI - [Not Available]. PMID- 21023391 TI - [Not Available]. PMID- 21023392 TI - [Not Available]. PMID- 21023393 TI - [Not Available]. PMID- 21023394 TI - [Not Available]. PMID- 21023395 TI - [Not Available]. PMID- 21023396 TI - [Not Available]. PMID- 21023397 TI - [Not Available]. PMID- 21023398 TI - [Not Available]. PMID- 21023399 TI - [Not Available]. PMID- 21023401 TI - Outdoor control of adult mosquitoes with DDT or pyrethrum applied with ground equipment. PMID- 21023400 TI - Facts and fallacies about DDT. PMID- 21023402 TI - Mosquitoes and other insects killed by aerial spraying with DDT in Panama. PMID- 21023403 TI - DDT applied with hand equipment for the control of salt-marsh mosquito larvae. PMID- 21023404 TI - Quick-breaking fuel-oil emulsions containing DDT. PMID- 21023405 TI - Tests on the airplane application of DDT for the control of adult mosquitoes in open, unwooded areas. PMID- 21023406 TI - Effectiveness of DDT as a residual treatment of bed nets. PMID- 21023407 TI - Composition of DDT products. PMID- 21023408 TI - The occurrence of Anopheles quadrimaculatus, Anopheles occidentalis and Anopheles walkeri in Vermont. PMID- 21023409 TI - Protecting marines from insectborne diseases. PMID- 21023410 TI - The use of DDT residual sprays in native Mexican homes for controlling Anopheles pseudopunctipennis mosquitoes. PMID- 21023411 TI - Diplodia rot of onions. PMID- 21023412 TI - Influence of nitrogen nutrition on susceptibility of onions to yellow-dwarf virus. PMID- 21023413 TI - A new bean mosaic in Idaho. PMID- 21023414 TI - Correlation between the possession of a chitinous cuticle and sensitivity to DDT. PMID- 21023415 TI - Protoplasmic viscosity changes in different regions of the grasshopper neuroblast during mitosis. PMID- 21023416 TI - Toxic effects of copper on attachment and growth of Bugula neritina. PMID- 21023417 TI - A new graphic method of describing the growth of animals. PMID- 21023418 TI - Investigation on the locus of action of DDT in flies (Drosophila). PMID- 21023419 TI - The contractile vacuole and the adjustment to changing concentration in fresh water amoebae. PMID- 21023421 TI - The concept of nerve-muscle specificity. PMID- 21023420 TI - The physiological significance of the phosphomonesterases. PMID- 21023422 TI - [Not Available]. PMID- 21023423 TI - [Not Available]. PMID- 21023424 TI - [Not Available]. PMID- 21023425 TI - [Not Available]. PMID- 21023426 TI - [Not Available]. PMID- 21023427 TI - [Not Available]. PMID- 21023428 TI - [Not Available]. PMID- 21023429 TI - [Not Available]. PMID- 21023430 TI - [Not Available]. PMID- 21023432 TI - [Not Available]. PMID- 21023431 TI - [Not Available]. PMID- 21023433 TI - [Not Available]. PMID- 21023434 TI - [Not Available]. PMID- 21023435 TI - [Not Available]. PMID- 21023436 TI - [Not Available]. PMID- 21023437 TI - [Not Available]. PMID- 21023438 TI - [Not Available]. PMID- 21023440 TI - [Not Available]. PMID- 21023439 TI - [Not Available]. PMID- 21023441 TI - [Not Available]. PMID- 21023443 TI - [Not Available]. PMID- 21023442 TI - [Not Available]. PMID- 21023444 TI - [Not Available]. PMID- 21023445 TI - [Not Available]. PMID- 21023446 TI - [Not Available]. PMID- 21023447 TI - [Not Available]. PMID- 21023448 TI - [Not Available]. PMID- 21023449 TI - [Not Available]. PMID- 21023450 TI - [Not Available]. PMID- 21023451 TI - [Not Available]. PMID- 21023452 TI - [Not Available]. PMID- 21023453 TI - [Not Available]. PMID- 21023454 TI - [Not Available]. PMID- 21023456 TI - [Not Available]. PMID- 21023455 TI - [Not Available]. PMID- 21023457 TI - [Not Available]. PMID- 21023458 TI - [Not Available]. PMID- 21023459 TI - [Not Available]. PMID- 21023460 TI - [Not Available]. PMID- 21023461 TI - [Not Available]. PMID- 21023462 TI - [Not Available]. PMID- 21023463 TI - [Not Available]. PMID- 21023464 TI - [Not Available]. PMID- 21023465 TI - [Not Available]. PMID- 21023466 TI - [Not Available]. PMID- 21023467 TI - [Not Available]. PMID- 21023468 TI - [Not Available]. PMID- 21023469 TI - [Not Available]. PMID- 21023470 TI - [Not Available]. PMID- 21023471 TI - [Not Available]. PMID- 21023472 TI - [Not Available]. PMID- 21023473 TI - [Not Available]. PMID- 21023474 TI - [Not Available]. PMID- 21023475 TI - [Not Available]. PMID- 21023476 TI - [Not Available]. PMID- 21023477 TI - [Not Available]. PMID- 21023478 TI - [Not Available]. PMID- 21023479 TI - [Not Available]. PMID- 21023480 TI - [Not Available]. PMID- 21023481 TI - [Not Available]. PMID- 21023482 TI - [Not Available]. PMID- 21023484 TI - [Not Available]. PMID- 21023483 TI - [Not Available]. PMID- 21023485 TI - [Not Available]. PMID- 21023486 TI - [Not Available]. PMID- 21023487 TI - [Not Available]. PMID- 21023488 TI - [Not Available]. PMID- 21023489 TI - [Not Available]. PMID- 21023490 TI - [Not Available]. PMID- 21023491 TI - [Not Available]. PMID- 21023492 TI - [Not Available]. PMID- 21023493 TI - [Not Available]. PMID- 21023494 TI - [Not Available]. PMID- 21023495 TI - [Not Available]. PMID- 21023496 TI - [Not Available]. PMID- 21023497 TI - [Not Available]. PMID- 21023498 TI - [Not Available]. PMID- 21023499 TI - [Not Available]. PMID- 21023500 TI - [Not Available]. PMID- 21023501 TI - [Not Available]. PMID- 21023502 TI - [Not Available]. PMID- 21023503 TI - [Not Available]. PMID- 21023504 TI - [Not Available]. PMID- 21023505 TI - [Not Available]. PMID- 21023506 TI - [Not Available]. PMID- 21023507 TI - [Not Available]. PMID- 21023508 TI - [Not Available]. PMID- 21023509 TI - [Not Available]. PMID- 21023510 TI - [Not Available]. PMID- 21023511 TI - [Not Available]. PMID- 21023512 TI - [Not Available]. PMID- 21023513 TI - [Not Available]. PMID- 21023514 TI - [Not Available]. PMID- 21023515 TI - [Not Available]. PMID- 21023516 TI - [Not Available]. PMID- 21023517 TI - [Not Available]. PMID- 21023518 TI - [Not Available]. PMID- 21023519 TI - [Not Available]. PMID- 21023520 TI - [Not Available]. PMID- 21023521 TI - [Not Available]. PMID- 21023522 TI - [Not Available]. PMID- 21023523 TI - [Not Available]. PMID- 21023524 TI - [Not Available]. PMID- 21023525 TI - [Not Available]. PMID- 21023526 TI - [Not Available]. PMID- 21023527 TI - [Not Available]. PMID- 21023528 TI - [Not Available]. PMID- 21023529 TI - [Not Available]. PMID- 21023530 TI - [Not Available]. PMID- 21023531 TI - [Not Available]. PMID- 21023532 TI - [Not Available]. PMID- 21023533 TI - [Not Available]. PMID- 21023534 TI - [Not Available]. PMID- 21023535 TI - [Not Available]. PMID- 21023536 TI - [Not Available]. PMID- 21023537 TI - [Not Available]. PMID- 21023538 TI - [Not Available]. PMID- 21023539 TI - [Not Available]. PMID- 21023540 TI - [Not Available]. PMID- 21023541 TI - [Not Available]. PMID- 21023543 TI - Thermal balance of men working in severe heat. PMID- 21023542 TI - The indirect determination of partial pressures in alveolar air. PMID- 21023544 TI - Changes of nerve properties near a killed region. PMID- 21023545 TI - Crash injuries in experimental animals (motion picture). PMID- 21023546 TI - The causation of the latency relaxation. PMID- 21023547 TI - Synaptic delay and central inhibition in relation to electrotonic potentials. PMID- 21023548 TI - Beta dimethylamino-ethyl benzhydryl ether hydrochloride as an antihistamine and anti-anaphylactic agent. PMID- 21023549 TI - The effects of smoking on the dark adaptation of rods and cones. PMID- 21023550 TI - Cortical autonomic center for the eyes on the mesial surface of the frontal lobe in cat. PMID- 21023551 TI - Maximum speed of movement as a test of muscle function in different nutritional states. PMID- 21023552 TI - Adrenal function following ovariectomy in the rat. PMID- 21023553 TI - Accuracy of indirect determinations of blood pressure in the rat; relation to temperature of the plethysmograph and width of cuff. PMID- 21023554 TI - The inhibition of enzyme formation. PMID- 21023555 TI - Abnormal forms of the ballistocardiogram. PMID- 21023556 TI - Observations on the synergistic effects of various antispasmodic compounds and nembutal on colon activity in normal adult males. PMID- 21023557 TI - An instantaneously recording cardiotachometer. PMID- 21023558 TI - The nature of circulating estrogen. PMID- 21023559 TI - Some effects of extreme heat and humidity on man. PMID- 21023560 TI - The effect of thiouracil administration on the succinoxidase and cytochrome oxidase of rat liver. PMID- 21023561 TI - Effect of serum and its fractions on acetylcholine synthesis. PMID- 21023562 TI - Protection against acceleratory forces by CO2 inhalation. PMID- 21023563 TI - The effect of unilateral renal artery constriction on the renin content of the contralateral kidney. PMID- 21023564 TI - The effects of ethyl alcohol on the isolated heart. PMID- 21023565 TI - Magnetic stimulation of the human retina. PMID- 21023566 TI - Reactions involved in insulin fibril formation. PMID- 21023567 TI - Liver function in malaria. PMID- 21023568 TI - Portal pressure gradients in hemorrhagic shock. PMID- 21023569 TI - Physiological effects of high negative mask pressures during simulated free-fall. PMID- 21023570 TI - The retention and excretion of continuously administered intravenous salt solutions in man. PMID- 21023571 TI - Electrical responses in gyrus cinguli evoked by electrical stimulation of ipsilateral mammillary body in cat and monkey. PMID- 21023572 TI - Correlation of electrical and mechanical events in the intestinal lumen of unanesthetized dogs. PMID- 21023573 TI - History of the nuclei of Tillina magna during division and encystment. PMID- 21023574 TI - The cytology of the Cecidomyidae (Diptera); polyploidy and polyteny in salivary gland cells of Lestodiplosis spp. PMID- 21023575 TI - A technique for counting numerous chromosomes. PMID- 21023576 TI - The development of the vascular pattern within the walls of the central nervous system of the chick embryo. PMID- 21023577 TI - Cleavage and attachment stages of the pig. PMID- 21023578 TI - [Not Available]. PMID- 21023579 TI - [Not Available]. PMID- 21023580 TI - [Not Available]. PMID- 21023581 TI - [Not Available]. PMID- 21023582 TI - [Not Available]. PMID- 21023583 TI - [Not Available]. PMID- 21023584 TI - [Not Available]. PMID- 21023585 TI - [Not Available]. PMID- 21023586 TI - [Not Available]. PMID- 21023587 TI - [Not Available]. PMID- 21023588 TI - [Not Available]. PMID- 21023589 TI - [Not Available]. PMID- 21023590 TI - [Not Available]. PMID- 21023591 TI - [Not Available]. PMID- 21023592 TI - [Not Available]. PMID- 21023594 TI - [Not Available]. PMID- 21023593 TI - [Not Available]. PMID- 21023595 TI - [Not Available]. PMID- 21023596 TI - [Not Available]. PMID- 21023597 TI - [Not Available]. PMID- 21023598 TI - [Not Available]. PMID- 21023599 TI - [Not Available]. PMID- 21023600 TI - The electrocardiogram of anginal attacks induced by exercise. PMID- 21023601 TI - [Not Available]. PMID- 21023602 TI - [Not Available]. PMID- 21023603 TI - [Not Available]. PMID- 21023605 TI - [Not Available]. PMID- 21023604 TI - [Not Available]. PMID- 21023606 TI - The breakdown of citric acid in different tissues. PMID- 21023607 TI - The preparation and properties of an amylase inhibitor of wheat. PMID- 21023608 TI - The mode of action of an amylase inhibitor from wheat. PMID- 21023609 TI - Fat formation in F. lycoperseci. PMID- 21023610 TI - The utilization of amino acids as a source of carbon by fungi. PMID- 21023611 TI - Additional and corrected data on the respiratory and fermentative activity of yeasts containing stored reserves. PMID- 21023612 TI - The nutritional role of acetate for lactic acid bacteria; the response to substances related to acetate. PMID- 21023613 TI - The nutritional role of acetate for lactic acid bacteria; fractionation of extracts of natural materials. PMID- 21023614 TI - The role of corn steep liquor in the production of penicillin. PMID- 21023615 TI - Relationship between the dose of factor N and the alcohol intake of rats under self-selection conditions. PMID- 21023616 TI - Enzymatic nature of cell-free extracts from bacteria. PMID- 21023617 TI - On the mechanism of enzyme action; the action of certain wood-destroying fungi on glucose, xylose, raffinose and cellulose. PMID- 21023618 TI - On the mechanism of enzyme action; application of resazurin to the study of dehydrogen-nations by certain merulii and Fomes annosus. PMID- 21023619 TI - Compounds active in correcting sulfonamide-induced granulocytopenia in rats. PMID- 21023620 TI - Note on the metabolism of some ribose derivatives. PMID- 21023621 TI - The story of antibiotics. PMID- 21023622 TI - The adsorption of strontium at forty degrees by enamel, dentin, bone, and hydroxyapatite as shown by the radioactive isotope. PMID- 21023623 TI - Enzymic nature of the carotene-destroying system of alfalfa. PMID- 21023624 TI - Manganese and l-leucine-aminoexopeptidase. PMID- 21023625 TI - Zinc toxicity in rats; antagonistic effects of copper and liver. PMID- 21023626 TI - Studies on cholinesterase; enzyme activity and voltage of the action potential in electric tissue. PMID- 21023627 TI - The synthesis and the enzymatic degradation of l-tyrosyl-l-lysyl-l-glutamyl-l tyrosine. PMID- 21023628 TI - On the mechanism of invasion; antinvasin I, an enzyme in plasma. PMID- 21023629 TI - On the mechanism of invasion; proinvasin I, an enzyme in pathogenic bacteria and in venoms. PMID- 21023630 TI - On the mechanism of invasion; antinvasin II, an enzyme in plasma. PMID- 21023631 TI - Ribonucleinase; the behavior of copper and calcium in the purification of nucleic acid and the effect of these and other reagents on the activity of ribonucleinase. PMID- 21023632 TI - Ribonucleinase; hydrolysis of ribonucleic acid by ribonucleinase and by sodium hydroxide. PMID- 21023633 TI - The microbiological determination of certain free amino acids in human and dog plasma. PMID- 21023634 TI - l-Hydroxy acid oxidase. PMID- 21023635 TI - The action of tyrosinase on proteins. PMID- 21023636 TI - Microbiological methods for the determination of amino acids; extension of the uniform assay method for the ten essential amino acids to include tyrosine. PMID- 21023637 TI - The synthesis of isocitric acid. PMID- 21023638 TI - The maintenance of nitrogen equilibrium in dogs by intravenous alimentation with an acid hydrolysate of casein fortified with tryptophane. PMID- 21023639 TI - The activity of dl-oxybiotin for the rat. PMID- 21023640 TI - The position of the higher fatty aldehydes in fatty acid metabolism of rat muscle. PMID- 21023641 TI - The nitrogen metabolism of rat tissue slices under various conditions. PMID- 21023642 TI - An electrophoretic analysis of changes produced in blood serum and plasma proteins by heat in the presence of sugars. PMID- 21023643 TI - Studies on the enzymatic systhesis of dextran from sucrose. PMID- 21023644 TI - Intestinal and liver factors in the metabolic utilization of homocystine. PMID- 21023645 TI - The influence of preexperimental food on the utilization of homocystine in a methyl-free diet. PMID- 21023646 TI - The antiinositol effect of gamma-hexachlorocyclohexane. PMID- 21023647 TI - The activity of Lactobacillus casei factor, folic acid, and vitamin Bc for Streptococcus faecalis and Lactobacillus casei. PMID- 21023648 TI - The mechanism of in vitro and in vivo inhibition of cholinesterase activity by diisopropyl fluorophosphate. PMID- 21023649 TI - Some culture studies on Lactobacillus arabinosus and Lactobacillus casei. PMID- 21023650 TI - Concentration of the rabbit papilloma virus with the Sharples supercentrifuge. PMID- 21023651 TI - The density and size of the rabbit papilloma virus. PMID- 21023652 TI - A rapid microdetermination of glycogen in tissue slices. PMID- 21023653 TI - Structural requirements for diabetogenic action in alloxan and related compounds. PMID- 21023654 TI - On the determination of plasma iodine. PMID- 21023655 TI - The determination of thyroxine in the thyroid gland of the rat. PMID- 21023656 TI - Methionine determination in proteins and foods. PMID- 21023657 TI - [Not Available]. PMID- 21023658 TI - [Not Available]. PMID- 21023659 TI - Recruitment and the dental schools. PMID- 21023660 TI - Failures in local anaesthesia. PMID- 21023661 TI - A macrodontic Bushman skull in relationship to a Boskopoid skull with a similar dentition and large jaws. PMID- 21023662 TI - A compound composite odontome. PMID- 21023663 TI - Acrylic dowel crown on re-implanted root. PMID- 21023664 TI - Notes on prosthetic procedures; a sectional method of flasking. PMID- 21023665 TI - Charcoal controls caries; an account of a survey of the incidence of dental caries in southern India. PMID- 21023666 TI - Dental caries and nutrition. PMID- 21023668 TI - [Not Available]. PMID- 21023667 TI - The evolution of the orthodontist's field. PMID- 21023669 TI - [Not Available]. PMID- 21023670 TI - The role of dental hygiene in a program of individual guidance. PMID- 21023671 TI - Fluorine-caries control study at Marshall and Jacksonville, Texas. PMID- 21023672 TI - The masticatory habits; an analysis of the number of chews when consuming food. PMID- 21023673 TI - Studies in periodontal disease; putrefactive organisms in the mouth. PMID- 21023674 TI - Whole saliva as a source of certain growth factors for an oral strain of Lactobacillus. PMID- 21023676 TI - Introduction of sodium iodide into the calcified dental tissues. PMID- 21023677 TI - Variability of the pain threshold in man. PMID- 21023675 TI - Sterilization effectiveness of a hot oil bath. PMID- 21023678 TI - A discussion of the amalgam restoration and its failures. PMID- 21023679 TI - Surgical correction of pronounced prognathism of the mandible. PMID- 21023680 TI - [Not Available]. PMID- 21023681 TI - [Not Available]. PMID- 21023682 TI - [Not Available]. PMID- 21023683 TI - [Not Available]. PMID- 21023684 TI - [Not Available]. PMID- 21023685 TI - [Not Available]. PMID- 21023686 TI - [Not Available]. PMID- 21023687 TI - [Not Available]. PMID- 21023688 TI - [Not Available]. PMID- 21023689 TI - [Not Available]. PMID- 21023690 TI - Problems in child dentistry. PMID- 21023691 TI - Practical periodontia. PMID- 21023692 TI - Operative dentistry. PMID- 21023694 TI - Stress breaking; effects of buccolingual attachments on removable partial dentures. PMID- 21023693 TI - The broken needle. PMID- 21023695 TI - Dermatitis. PMID- 21023696 TI - [Not Available]. PMID- 21023697 TI - [Not Available]. PMID- 21023698 TI - [Not Available]. PMID- 21023699 TI - [Not Available]. PMID- 21023700 TI - [Not Available]. PMID- 21023702 TI - [Not Available]. PMID- 21023701 TI - [Not Available]. PMID- 21023703 TI - [Not Available]. PMID- 21023704 TI - [Not Available]. PMID- 21023705 TI - Orthodontics today. PMID- 21023706 TI - Dental equipment and the veteran. PMID- 21023707 TI - Organized dentistry's responsibilities today. PMID- 21023708 TI - Dermatophytosis and other forms of intertriginous dermatitis of the feet; a comparison of therapeutic method. PMID- 21023709 TI - Penicillin ointment in the treatment of some infections of the skin. PMID- 21023710 TI - Acne indurata in identical twins treated by penicillin. PMID- 21023711 TI - Penicillin in topical treatment of pyogenic infections of the skin; clinical and laboratory observations. PMID- 21023712 TI - Tokelau in Guatemala. PMID- 21023713 TI - Pemphigus vulgaris; successful results following transfusion with blood from persons who had recovered from the disease. PMID- 21023714 TI - Sporotrichosis with radiate formation in tissue; report of a case. PMID- 21023715 TI - Contact dermatitis; an analysis or tabulation of all cases proved in a single year. PMID- 21023716 TI - Keratosis blennorrhagica; its response to penicillin. PMID- 21023717 TI - Theophylline ethylenediamine as an antipruritic agent. PMID- 21023718 TI - Blue nevus of Jadassohn and Tieche; report of a case. PMID- 21023719 TI - Verruca plana juvenilis. PMID- 21023720 TI - Malignant melanoma. PMID- 21023721 TI - Circumscribed scleroderma. PMID- 21023722 TI - A case for diagnosis (sarcoidosis?). PMID- 21023723 TI - Xeroderma pigmentosum. PMID- 21023724 TI - A case for diagnosis (eczema? simulating leprosy). PMID- 21023725 TI - Hydroa estivale. PMID- 21023726 TI - Dermatitis herpetiformis. PMID- 21023727 TI - Fox-Fordyce disease. PMID- 21023728 TI - [Not Available]. PMID- 21023729 TI - [Not Available]. PMID- 21023730 TI - [Not Available]. PMID- 21023731 TI - [Not Available]. PMID- 21023732 TI - [Not Available]. PMID- 21023733 TI - [Not Available]. PMID- 21023734 TI - [Not Available]. PMID- 21023735 TI - [Not Available]. PMID- 21023736 TI - [Not Available]. PMID- 21023737 TI - [Not Available]. PMID- 21023738 TI - [Not Available]. PMID- 21023739 TI - [Not Available]. PMID- 21023740 TI - [Not Available]. PMID- 21023741 TI - [Not Available]. PMID- 21023742 TI - Normal blood pressure in senescence; a study of 3691 white male subjects between the ages of 50 and 95 years. PMID- 21023743 TI - Transurethral prostatic resection on elderly patients. PMID- 21023746 TI - The senile and prematurely senile skin. PMID- 21023745 TI - Guillain-Barre's disease in the older age group. PMID- 21023744 TI - Pancreatitis in geriatric practice. PMID- 21023747 TI - Some prophylactic suggestions regarding the science of geriatrics. PMID- 21023748 TI - Cardiovascular deterioration. PMID- 21023749 TI - A new method of local treatment of rheumatoid and traumatic affections of the joints. PMID- 21023750 TI - Blood disorders associated with pregnancy; the value of sternal marrow biopsy. PMID- 21023751 TI - Studies on the red fluorescent porphyrin deposits on vagina and cervix; a possible aid in the detection of malignancy. PMID- 21023752 TI - Studies on high dosage progesterone therapy of amenorrhea. PMID- 21023753 TI - A review of the maternal mortality at the Chicago Lying-in Hospital, 1931-1945. PMID- 21023754 TI - The evolution of the biologic concept of the etiology of late toxemia. PMID- 21023755 TI - A paravesical extraperitoneal cesarean section technique; with an analysis of 160 paravesical extraperitoneal cesarean sections. PMID- 21023756 TI - A case of Clostridium welchii puerperal infection treated with penicillin. PMID- 21023757 TI - Vaginal hysterectomy; a record of results based on the Weir technique. PMID- 21023758 TI - The measurement of the diameters of the pelvic outlet. PMID- 21023759 TI - The psychosomatic treatment of hyperemesis gravidarum by hypnosis. PMID- 21023760 TI - The mechanism of the histidinuria of pregnancy. PMID- 21023761 TI - Granulosa-cell tumor of the ovary; report of five cases with premature menopause (amenorrhea) and the recurrence of menstruation. PMID- 21023762 TI - Infectious mononucleosis complicating pregnancy. PMID- 21023763 TI - Use of curare to relieve dysmenorrhea. PMID- 21023764 TI - Early clinical and roentgenologic diagnosis of anencephaly. PMID- 21023765 TI - Argentaffin carcinoma (carcinoid tumor) arising in an ovarian dermoid cyst. PMID- 21023766 TI - Recurrent placenta previa and the significance of placentography as a diagnostic criterion. PMID- 21023767 TI - Vestibular abnormal anus in a pregnant woman. PMID- 21023768 TI - Opisthotonus fetalis. PMID- 21023769 TI - [Not Available]. PMID- 21023770 TI - [Not Available]. PMID- 21023771 TI - [Not Available]. PMID- 21023772 TI - [Not Available]. PMID- 21023773 TI - [Not Available]. PMID- 21023774 TI - [Not Available]. PMID- 21023775 TI - [Not Available]. PMID- 21023777 TI - [Not Available]. PMID- 21023778 TI - [Not Available]. PMID- 21023776 TI - [Not Available]. PMID- 21023779 TI - [Not Available]. PMID- 21023780 TI - [Not Available]. PMID- 21023781 TI - [Not Available]. PMID- 21023782 TI - [Not Available]. PMID- 21023784 TI - [Not Available]. PMID- 21023783 TI - [Not Available]. PMID- 21023785 TI - [Not Available]. PMID- 21023786 TI - [Not Available]. PMID- 21023787 TI - [Not Available]. PMID- 21023788 TI - [Not Available]. PMID- 21023789 TI - [Not Available]. PMID- 21023790 TI - [Not Available]. PMID- 21023791 TI - [Not Available]. PMID- 21023792 TI - [Not Available]. PMID- 21023793 TI - [Not Available]. PMID- 21023794 TI - [Not Available]. PMID- 21023795 TI - [Not Available]. PMID- 21023796 TI - [Not Available]. PMID- 21023797 TI - [Not Available]. PMID- 21023798 TI - [Not Available]. PMID- 21023799 TI - [Not Available]. PMID- 21023800 TI - [Not Available]. PMID- 21023801 TI - [Not Available]. PMID- 21023802 TI - [Not Available]. PMID- 21023803 TI - [Not Available]. PMID- 21023804 TI - [Not Available]. PMID- 21023805 TI - [Not Available]. PMID- 21023806 TI - [Not Available]. PMID- 21023808 TI - [Not Available]. PMID- 21023807 TI - [Not Available]. PMID- 21023809 TI - [Not Available]. PMID- 21023810 TI - [Not Available]. PMID- 21023811 TI - [Not Available]. PMID- 21023812 TI - [Not Available]. PMID- 21023813 TI - [Not Available]. PMID- 21023814 TI - [Not Available]. PMID- 21023815 TI - [Not Available]. PMID- 21023816 TI - [Not Available]. PMID- 21023817 TI - [Not Available]. PMID- 21023818 TI - [Not Available]. PMID- 21023819 TI - [Not Available]. PMID- 21023820 TI - [Not Available]. PMID- 21023821 TI - [Not Available]. PMID- 21023822 TI - [Not Available]. PMID- 21023823 TI - [Not Available]. PMID- 21023824 TI - [Not Available]. PMID- 21023825 TI - [Not Available]. PMID- 21023826 TI - [Not Available]. PMID- 21023827 TI - [Not Available]. PMID- 21023828 TI - [Not Available]. PMID- 21023829 TI - [Not Available]. PMID- 21023830 TI - [Not Available]. PMID- 21023831 TI - [Not Available]. PMID- 21023832 TI - [Not Available]. PMID- 21023833 TI - [Not Available]. PMID- 21023834 TI - [Not Available]. PMID- 21023835 TI - [Not Available]. PMID- 21023836 TI - [Not Available]. PMID- 21023837 TI - [Not Available]. PMID- 21023838 TI - Management of a case of retained placenta. PMID- 21023839 TI - A case of missed labour. PMID- 21023840 TI - Vaginal fistulae and recto vaginal fistulae. PMID- 21023841 TI - Functional bleeding of uterus. PMID- 21023842 TI - The role of inflammation in the private practice. PMID- 21023844 TI - The use of masks in midwifery. PMID- 21023843 TI - Analgesia and anaesthesia in obstetrics. PMID- 21023845 TI - [Not Available]. PMID- 21023846 TI - [Not Available]. PMID- 21023847 TI - [Not Available]. PMID- 21023848 TI - [Not Available]. PMID- 21023849 TI - [Not Available]. PMID- 21023850 TI - [Not Available]. PMID- 21023851 TI - [Not Available]. PMID- 21023852 TI - [Not Available]. PMID- 21023853 TI - [Not Available]. PMID- 21023854 TI - [Not Available]. PMID- 21023855 TI - [Not Available]. PMID- 21023856 TI - [Not Available]. PMID- 21023857 TI - [Not Available]. PMID- 21023858 TI - [Not Available]. PMID- 21023859 TI - [Not Available]. PMID- 21023860 TI - [Not Available]. PMID- 21023861 TI - [Not Available]. PMID- 21023862 TI - [Not Available]. PMID- 21023863 TI - [Not Available]. PMID- 21023864 TI - [Not Available]. PMID- 21023865 TI - [Not Available]. PMID- 21023866 TI - Interior decoration in the hospital. PMID- 21023867 TI - Hospital planning; preliminary stages. PMID- 21023868 TI - Food in American hospitals. PMID- 21023869 TI - Sterilizing and disinfecting. PMID- 21023870 TI - [Not Available]. PMID- 21023871 TI - [Not Available]. PMID- 21023872 TI - [Not Available]. PMID- 21023873 TI - [Not Available]. PMID- 21023874 TI - [Not Available]. PMID- 21023875 TI - [Not Available]. PMID- 21023876 TI - [Not Available]. PMID- 21023877 TI - [Not Available]. PMID- 21023878 TI - [Not Available]. PMID- 21023879 TI - [Not Available]. PMID- 21023880 TI - [Not Available]. PMID- 21023881 TI - [Not Available]. PMID- 21023882 TI - [Not Available]. PMID- 21023883 TI - [Not Available]. PMID- 21023885 TI - [Not Available]. PMID- 21023884 TI - [Not Available]. PMID- 21023886 TI - [Not Available]. PMID- 21023887 TI - [Not Available]. PMID- 21023888 TI - [Not Available]. PMID- 21023889 TI - [Not Available]. PMID- 21023890 TI - [Not Available]. PMID- 21023891 TI - Psychosomatic consultations in industry. PMID- 21023892 TI - Compensable hernia; the problems in the average state. PMID- 21023893 TI - Use and abuse of radiographs in the diagnosis of mouth infection. PMID- 21023894 TI - Paraprol in industrial dermatitis. PMID- 21023895 TI - Silica hazard in arc furnace construction. PMID- 21023896 TI - Health facilities in New Jersey plants. PMID- 21023897 TI - On the use of radioactive tracers in industrial medicine. PMID- 21023898 TI - Mental hygiene problems in vocational rehabilitation. PMID- 21023899 TI - Effects of electrical injuries, with particular reference to the nervous system. PMID- 21023900 TI - Medicolegal aspects of injuries from exposure to roentgen rays and radioactive substances. PMID- 21023901 TI - Tuberculosis in industry from the viewpoint of the physician in industry. PMID- 21023902 TI - [Not Available]. PMID- 21023903 TI - [Not Available]. PMID- 21023904 TI - [Not Available]. PMID- 21023906 TI - [Not Available]. PMID- 21023905 TI - [Not Available]. PMID- 21023907 TI - [Not Available]. PMID- 21023908 TI - [Not Available]. PMID- 21023909 TI - [Not Available]. PMID- 21023910 TI - [Not Available]. PMID- 21023911 TI - [Not Available]. PMID- 21023912 TI - [Not Available]. PMID- 21023914 TI - [Not Available]. PMID- 21023913 TI - [Not Available]. PMID- 21023915 TI - [Not Available]. PMID- 21023916 TI - [Not Available]. PMID- 21023917 TI - [Not Available]. PMID- 21023918 TI - [Not Available]. PMID- 21023919 TI - [Not Available]. PMID- 21023920 TI - [Not Available]. PMID- 21023921 TI - [Not Available]. PMID- 21023922 TI - [Not Available]. PMID- 21023923 TI - [Not Available]. PMID- 21023924 TI - Carcinoma of the cervix uteri. PMID- 21023925 TI - Surgery of the heart. PMID- 21023926 TI - The management of obstructive lesions of the colon. PMID- 21023927 TI - Refractory pernicious anemia. PMID- 21023928 TI - The indications and limitations of the electrocardiogram. PMID- 21023929 TI - [Not Available]. PMID- 21023930 TI - [Not Available]. PMID- 21023931 TI - [Not Available]. PMID- 21023932 TI - The surgical treatment of chronic duodenal ulcer. PMID- 21023933 TI - The stimulus of war to cardiology. PMID- 21023934 TI - The rationale of portacaval anastomosis. PMID- 21023935 TI - Portacaval anastomosis; a report on 14 cases. PMID- 21023936 TI - A review of 401 cases of early ambulation. PMID- 21023937 TI - Combined penicillin and heparin therapy of subacute bacterial endocarditis. PMID- 21023938 TI - [Not Available]. PMID- 21023939 TI - [Not Available]. PMID- 21023940 TI - [Not Available]. PMID- 21023941 TI - [Not Available]. PMID- 21023942 TI - [Not Available]. PMID- 21023943 TI - [Not Available]. PMID- 21023944 TI - [Not Available]. PMID- 21023945 TI - [Not Available]. PMID- 21023946 TI - [Not Available]. PMID- 21023947 TI - [Not Available]. PMID- 21023948 TI - [Not Available]. PMID- 21023949 TI - [Not Available]. PMID- 21023950 TI - [Not Available]. PMID- 21023951 TI - [Not Available]. PMID- 21023952 TI - [Not Available]. PMID- 21023953 TI - [Not Available]. PMID- 21023954 TI - [Not Available]. PMID- 21023955 TI - [Not Available]. PMID- 21023956 TI - [Not Available]. PMID- 21023957 TI - [Not Available]. PMID- 21023958 TI - [Not Available]. PMID- 21023959 TI - [Not Available]. PMID- 21023960 TI - [Not Available]. PMID- 21023961 TI - Determination of the effect of irradiation by x-ray on p-aminobenzoic acid, using Clostridium acetobutylicum for assay. PMID- 21023962 TI - Collecting and handling mosquitoes on Western equine encephalitis investigations in Manitoba. PMID- 21023963 TI - Multiple feeding habits of Saskatchewan mosquitoes. PMID- 21023964 TI - The reduction of hydrogen peroxide by fibrin. PMID- 21023965 TI - The serological relationships of the rickettsiae of epidemic and murine typhus. PMID- 21023966 TI - Treatment of epilepsy. PMID- 21023968 TI - Clinical pathological conference. PMID- 21023967 TI - Variations of primary atypical pneumonia. PMID- 21023969 TI - [Not Available]. PMID- 21023970 TI - [Not Available]. PMID- 21023971 TI - [Not Available]. PMID- 21023972 TI - [Not Available]. PMID- 21023973 TI - [Not Available]. PMID- 21023974 TI - [Not Available]. PMID- 21023975 TI - [Not Available]. PMID- 21023976 TI - [Not Available]. PMID- 21023977 TI - The copper sulphate method in routine haematological examinations. PMID- 21023978 TI - The surgical treatment of deafness. PMID- 21023979 TI - Two-stage treatment of soft tissue injuries. PMID- 21023980 TI - Fracture-dislocation of mandible. PMID- 21023981 TI - Calcification of placenta. PMID- 21023982 TI - The uses of amnioplastin. PMID- 21023983 TI - The relationship of tuberculosis and silicosis. PMID- 21023984 TI - Histoplasmin skin sensitivity and pulmonary calcifications; a review. PMID- 21023985 TI - Tuberculosis control depends upon the practicing physician. PMID- 21023986 TI - Facts and inferences of Minnesota Sanatorium admittances. PMID- 21023987 TI - The hazard of tuberculosis during medical training; an abridged report of a case finding and follow-up regime among women medical students, with an effective control program against tuberculosis. PMID- 21023988 TI - The out-patient chest clinic. PMID- 21023989 TI - Who should have the tuberculin test? PMID- 21023990 TI - Report of a one-year survey of a diagnostic tuberculosis service in a general hospital. PMID- 21023991 TI - Caudal block anesthesia and the general practitioner. PMID- 21023992 TI - Tuberculosis survey of the prison populations of Alabama. PMID- 21023993 TI - Simultaneous splenectomy and nephrectomy; report of case. PMID- 21023994 TI - A cancer detection clinic in industry; a preliminary report. PMID- 21023996 TI - [Not Available]. PMID- 21023997 TI - [Not Available]. PMID- 21023995 TI - [Not Available]. PMID- 21023998 TI - [Not Available]. PMID- 21023999 TI - [Not Available]. PMID- 21024000 TI - [Not Available]. PMID- 21024001 TI - [Not Available]. PMID- 21024002 TI - [Not Available]. PMID- 21024003 TI - [Not Available]. PMID- 21024004 TI - [Not Available]. PMID- 21024006 TI - [Not Available]. PMID- 21024005 TI - [Not Available]. PMID- 21024007 TI - [Not Available]. PMID- 21024008 TI - [Not Available]. PMID- 21024009 TI - [Not Available]. PMID- 21024010 TI - [Not Available]. PMID- 21024011 TI - [Not Available]. PMID- 21024012 TI - [Not Available]. PMID- 21024013 TI - [Not Available]. PMID- 21024014 TI - [Not Available]. PMID- 21024015 TI - Prepaid medical care. PMID- 21024016 TI - Eczematous and pigmentary lichenoid dermatitis (atypical lichen planus). PMID- 21024018 TI - Trauma as a cause of cancer. PMID- 21024017 TI - Loss of vision in patients with hypertensive disease and with diabetes. PMID- 21024019 TI - Maladjustment in the returning veteran; comments on etiology and symptomatology. PMID- 21024020 TI - Determination of operability of cancer of the stomach with the abdomen opened. PMID- 21024021 TI - A new type of T-tube for surgery of the biliary tract. PMID- 21024022 TI - Prefrontal lobotomy for intractable pain; case report. PMID- 21024023 TI - Treatment of resistant paroxysmal auricular tachycardia with prostigmine followed by mecholyl. PMID- 21024024 TI - Massive hemorrhage in peptic ulcer, controlled by operation; report of a case. PMID- 21024025 TI - Orthostatic hypotension. PMID- 21024026 TI - Courvoisier's law. PMID- 21024027 TI - [Not Available]. PMID- 21024028 TI - [Not Available]. PMID- 21024030 TI - [Not Available]. PMID- 21024029 TI - Granuloma anular (eritema elevatum diutinum) e diabetes. PMID- 21024031 TI - [Not Available]. PMID- 21024032 TI - [Not Available]. PMID- 21024033 TI - [Not Available]. PMID- 21024034 TI - [Not Available]. PMID- 21024035 TI - [Not Available]. PMID- 21024036 TI - [Not Available]. PMID- 21024037 TI - [Not Available]. PMID- 21024038 TI - [Not Available]. PMID- 21024039 TI - [Not Available]. PMID- 21024040 TI - [Not Available]. PMID- 21024042 TI - [Not Available]. PMID- 21024041 TI - [Not Available]. PMID- 21024044 TI - [Not Available]. PMID- 21024043 TI - [Not Available]. PMID- 21024045 TI - [Not Available]. PMID- 21024046 TI - [Not Available]. PMID- 21024047 TI - [Not Available]. PMID- 21024048 TI - [Not Available]. PMID- 21024049 TI - [Not Available]. PMID- 21024050 TI - [Not Available]. PMID- 21024051 TI - [Not Available]. PMID- 21024053 TI - [Not Available]. PMID- 21024052 TI - [Not Available]. PMID- 21024054 TI - [Not Available]. PMID- 21024055 TI - [Not Available]. PMID- 21024056 TI - Spinal analgesia. PMID- 21024057 TI - Penicillin therapy for tendon sheath infections of the hand. PMID- 21024058 TI - Stained smears for the rapid diagnosis of infections due to Streptococcus haemolyticus group A following childbirth and abortion. PMID- 21024059 TI - Report of a case of Salmonella blegdam septicaemia and suppurative pericarditis with recovery. PMID- 21024060 TI - Penicillin in pre-operative and post-operative ophthalmic surgery. PMID- 21024061 TI - A jungle appendicectomy. PMID- 21024062 TI - RESEARCH in medical history. PMID- 21024063 TI - Facts and figures on cancer of the cervix and endometrium and the incidence of these diseases in a metropolitan city of Texas. PMID- 21024064 TI - Kymographic tracing instead of endometrial biopsy for the determination of ovulation. PMID- 21024065 TI - Peptic ulcer. PMID- 21024066 TI - Pleural mesothelioma; with report of a case presenting some unusual aspects. PMID- 21024067 TI - Postpartum hemorrhage. PMID- 21024068 TI - Early treatment of injuries to the knee joint. PMID- 21024069 TI - Spastic paraplegias. PMID- 21024070 TI - Lesions of the posterior urethra and bladder-neck as common causes of disturbances of micturition. PMID- 21024071 TI - Stammering. PMID- 21024072 TI - Toxic goiter and its conservative treatment. PMID- 21024073 TI - Arthritis deformans as an endocrine disease. PMID- 21024074 TI - Herewith is outlined a safe rural obstetric service. PMID- 21024075 TI - The management of rheumatic fever. PMID- 21024077 TI - The treatment of tumors occurring in male breasts. PMID- 21024076 TI - The care of the premature infant. PMID- 21024078 TI - Cholecystectomy: its origin and present status. PMID- 21024079 TI - Acute lesions of the abdomen; diagnosis and treatment. PMID- 21024080 TI - The use of myristyl-gammapicolinium chloride in surgery. PMID- 21024081 TI - Tuberculous pericarditis; incidence at Glen Lake Sanatorium. PMID- 21024082 TI - The acceleration of bone production by use of ground bone. PMID- 21024083 TI - Gallstone ileus; report of case. PMID- 21024084 TI - Malignant tumors of the kidney. PMID- 21024085 TI - Diphtheria; a report of six deaths. PMID- 21024086 TI - Clinical and laboratory studies of relapsing vivax malaria of Pacific origin. PMID- 21024087 TI - Longevity with ventricular aneurysm; report of a case with a survival period of 15 years. PMID- 21024088 TI - Osseous Gaucher's disease with macrocytic normochromic anemia; report of a case. PMID- 21024089 TI - Surgery of the heart and structures related to it. PMID- 21024090 TI - Neurinoma of stomach. PMID- 21024091 TI - Carcinoma of stomach. PMID- 21024092 TI - Properties, preparation and clinical application of penicillin. PMID- 21024093 TI - The problem of trachoma in Czechoslovakia. PMID- 21024094 TI - Scheme for an expanded and completed child welfare service in postwar Czechoslovakia. PMID- 21024095 TI - Child psychiatry and its postwar problems. PMID- 21024096 TI - Towards a broader industrial medicine. PMID- 21024098 TI - Functional regeneration of peripheral nerves. PMID- 21024097 TI - On the question of teaching venereal disease in medical schools. PMID- 21024099 TI - Czech doctors in Great Britain. PMID- 21024100 TI - The neurological examination. PMID- 21024101 TI - Eye lessons in general practice. PMID- 21024102 TI - Outbreak of typhoid fever in Trenton, Nova Scotia. PMID- 21024103 TI - The therapeutic use of procaine in minor surgical conditions. PMID- 21024104 TI - Urinary tract pathology engendered by changes in the generative system. PMID- 21024105 TI - [Not Available]. PMID- 21024106 TI - [Not Available]. PMID- 21024107 TI - [Not Available]. PMID- 21024108 TI - [Not Available]. PMID- 21024109 TI - [Not Available]. PMID- 21024110 TI - [Not Available]. PMID- 21024111 TI - [Not Available]. PMID- 21024112 TI - [Not Available]. PMID- 21024113 TI - [Not Available]. PMID- 21024114 TI - Observations in mainland clinics, September-December, 1945. PMID- 21024115 TI - Mononucleosis, the imitator; a case report. PMID- 21024116 TI - The histologic changes and distribution of organisms in the local lesion of tetanus; pathologic study of a case. PMID- 21024117 TI - Peritonitis following malignant obstruction of sigmoid and free perforation; report of three cases. PMID- 21024118 TI - The effect of vagotomy and partial gastrectomy on gastric acidity; effect of stimulation of the psychic phase in presence of tenth-normal hydrochloric acid in the stomach. PMID- 21024119 TI - Results in a case of spondylolisthesis eight years after spinal fusion. PMID- 21024120 TI - The roentgenographic aspects of polycythemia vera. PMID- 21024121 TI - Recurring gastro-intestinal hemorrhage in hereditary hemorrhagic telangiectasia; incidence and report of a case. PMID- 21024122 TI - Discussion on the methods to be employed in eradicating tuberculosis of bovine origin from the human and animal populations. PMID- 21024123 TI - Pityriasis rubra pilaris with ainhum and syringomyelia. PMID- 21024124 TI - Lupus vulgaris treated with calciferol. PMID- 21024125 TI - Kaposi's idiopathic sarcoma. PMID- 21024126 TI - Black hairy tongue. PMID- 21024127 TI - Multiple keloids following varicella. PMID- 21024128 TI - Xanthoma of hands. PMID- 21024129 TI - Sense and sensibility in the treatment of cancer. PMID- 21024130 TI - Discussion on abdominal incisions. PMID- 21024131 TI - Penicillin in ophthalmology. PMID- 21024132 TI - Neuro-retinitis of unknown origin. PMID- 21024133 TI - Ocular myiasis. PMID- 21024134 TI - Plastic artificial eyes. PMID- 21024135 TI - Some aspects of the normal histology of the suspensory ligament of the lens. PMID- 21024136 TI - The nervus nasalis complex of Charlin. PMID- 21024138 TI - Vestibular injuries. PMID- 21024137 TI - Cochlear deafness. PMID- 21024139 TI - Rehabilitation in vestibular injuries. PMID- 21024140 TI - Discussion on penicillin in rhinology. PMID- 21024141 TI - Personnel selection: by whom? PMID- 21024142 TI - Influence of thiourea on organ weights of rats as related to food intake. PMID- 21024143 TI - Temperature coefficients of hemolysis of a few types of nucleated erythrocytes. PMID- 21024144 TI - Isolation of St. Louis encephalitis virus from a fatal human case in California. PMID- 21024145 TI - Elimination in human feces of infectious hepatitis virus parenterally introduced. PMID- 21024146 TI - Transplantability of induced granulosa cell tumors and of luteoma in mice; secondary effects of these growths. PMID- 21024147 TI - A method for detection of streptothricin in the presence of streptomycin. PMID- 21024148 TI - Biological conversion of n-butyl penicillin into a chemotherapeutically active substance. PMID- 21024149 TI - Influence of iron salts on the toxicity of lead. PMID- 21024150 TI - Influence of certain substances on activity of streptomycin; modifications in test medium. PMID- 21024151 TI - Metabolism of glycine by the completely isolated mammalian heart investigated with carboxyl-labeled glycine. PMID- 21024152 TI - Blood and tissue chemical studies in fowl. PMID- 21024153 TI - Experimental tubular nephritis produced by safranin O. PMID- 21024154 TI - Potassium deficiency in the dog. PMID- 21024155 TI - Antigenic relationship of Shigella dispar, types I and II, to Shigella paradysenteriae, Boyd type P143. PMID- 21024156 TI - Immunity following para-aminobenzoic acid therapy in experimental tsutsugamushi disease (scrub typhus). PMID- 21024157 TI - Natural occurrence of an induced antigen in Salmonella cultures. PMID- 21024158 TI - Production of staphylococcal enterotoxin in chemically defined media. PMID- 21024159 TI - Bone tumors in fowls injected intravenously with causative agent of Rous sarcoma. PMID- 21024161 TI - Effect of penicillin on blood urea in the rat. PMID- 21024160 TI - Development of tolerance to typhoid bacterial pyrogen and its abolition by reticulo-endothelial blockade. PMID- 21024162 TI - Nervous system mechanism for epinephrine secretion. PMID- 21024163 TI - Inhibition of experimental drug allergy by prior feeding of the sensitizing agent. PMID- 21024164 TI - Rabbit papilloma and vaccinia viruses and T2 bacteriophage of E. coli in shadow electron micrographs. PMID- 21024165 TI - Attempts to propagate murine poliomyelitis virus on various intestinal bacteria and protozoa. PMID- 21024166 TI - Effect of thiourea on development of the sea urchin, Arbacia punctulata. PMID- 21024167 TI - Effect of elevated body temperature on plasma vitamin A and carotene. PMID- 21024168 TI - Demonstration of infectious hepatitis virus in presymptomatic period after transfer by transfusion. PMID- 21024170 TI - Experimental sinoauricular block. PMID- 21024169 TI - Sources of energy for intestinal smooth muscle contraction. PMID- 21024171 TI - Respiration in Macaca mulatta (Rhesus monkey). PMID- 21024172 TI - Relative growth of the kidney in male rats. PMID- 21024174 TI - Observations on rats fed with Yellow A.B. PMID- 21024173 TI - Kidney hypertrophy in B complex deficiency. PMID- 21024175 TI - Effect of choline on blood and tissues with especial reference to cholesterol in old hens. PMID- 21024176 TI - Japanese B encephalitis virus in the blood of experimentally inoculated chickens. PMID- 21024177 TI - Studies on scrub typhus; preparation of formalinized vaccines from tissues of infected mice and rats. PMID- 21024178 TI - Preparation of an inactivated tissue culture scrub typhus vaccine. PMID- 21024179 TI - A convenient test animal for the detection of the leukocytosis-promoting factor of exudates. PMID- 21024180 TI - [Not Available]. PMID- 21024181 TI - [Not Available]. PMID- 21024182 TI - [Not Available]. PMID- 21024183 TI - [Not Available]. PMID- 21024184 TI - [Not Available]. PMID- 21024185 TI - [Not Available]. PMID- 21024186 TI - [Not Available]. PMID- 21024187 TI - [Not Available]. PMID- 21024188 TI - [Not Available]. PMID- 21024189 TI - [Not Available]. PMID- 21024190 TI - [Not Available]. PMID- 21024191 TI - [Not Available]. PMID- 21024192 TI - [Not Available]. PMID- 21024193 TI - [Not Available]. PMID- 21024194 TI - [Not Available]. PMID- 21024195 TI - [Not Available]. PMID- 21024196 TI - [Not Available]. PMID- 21024197 TI - [Not Available]. PMID- 21024198 TI - The present status of the surgical treatment of cancer of the rectum and pelvic colon. PMID- 21024199 TI - [Not Available]. PMID- 21024200 TI - [Not Available]. PMID- 21024201 TI - [Not Available]. PMID- 21024202 TI - [Not Available]. PMID- 21024203 TI - [Not Available]. PMID- 21024204 TI - [Not Available]. PMID- 21024205 TI - [Not Available]. PMID- 21024206 TI - [Not Available]. PMID- 21024207 TI - [Not Available]. PMID- 21024209 TI - [Not Available]. PMID- 21024208 TI - [Not Available]. PMID- 21024211 TI - Extra-sanatorium pneumotherapy; an aid in the management of active pulmonary tuberculosis. PMID- 21024210 TI - Practical gynecological endocrinology. PMID- 21024212 TI - Abdominal puncture; a practical aid in diagnosis. PMID- 21024213 TI - [Not Available]. PMID- 21024214 TI - [Not Available]. PMID- 21024215 TI - [Not Available]. PMID- 21024216 TI - [Not Available]. PMID- 21024217 TI - [Not Available]. PMID- 21024218 TI - [Not Available]. PMID- 21024219 TI - [Not Available]. PMID- 21024220 TI - [Not Available]. PMID- 21024221 TI - [Not Available]. PMID- 21024222 TI - [Not Available]. PMID- 21024223 TI - [Not Available]. PMID- 21024224 TI - [Not Available]. PMID- 21024225 TI - [Not Available]. PMID- 21024226 TI - [Not Available]. PMID- 21024227 TI - [Not Available]. PMID- 21024228 TI - [Not Available]. PMID- 21024229 TI - [Not Available]. PMID- 21024230 TI - [Not Available]. PMID- 21024231 TI - [Not Available]. PMID- 21024233 TI - [Not Available]. PMID- 21024232 TI - [Not Available]. PMID- 21024234 TI - [Not Available]. PMID- 21024235 TI - [Not Available]. PMID- 21024236 TI - [Not Available]. PMID- 21024237 TI - [Not Available]. PMID- 21024238 TI - [Not Available]. PMID- 21024239 TI - [Not Available]. PMID- 21024240 TI - [Not Available]. PMID- 21024241 TI - [Not Available]. PMID- 21024242 TI - [Not Available]. PMID- 21024243 TI - [Not Available]. PMID- 21024244 TI - [Not Available]. PMID- 21024245 TI - [Not Available]. PMID- 21024246 TI - The diffusion of electrolytes and macromolecules in solution; a historical survey. PMID- 21024247 TI - Theories and problems of liquid diffusion. PMID- 21024248 TI - A conductance method for the determination of the diffusion coefficients of electrolytes. PMID- 21024249 TI - The diaphragm cell method of measuring diffusion. PMID- 21024251 TI - The effects of concentration and polydispersity on the diffusion coefficients of high polymers. PMID- 21024250 TI - Diffusion constant measurement in theory and practice. PMID- 21024252 TI - [Not Available]. PMID- 21024253 TI - [Not Available]. PMID- 21024254 TI - [Not Available]. PMID- 21024255 TI - The effect of DDT on the stem rust reaction of Khapli wheat. PMID- 21024256 TI - [Not Available]. PMID- 21024257 TI - [Not Available]. PMID- 21024259 TI - Some thoughts on nomenclature. PMID- 21024258 TI - AMINO-SUGARS and uronic acids in nature. PMID- 21024260 TI - Osmotic pressure of rod-shaped particles in solution. PMID- 21024261 TI - Molecular weight distribution of proteins. PMID- 21024262 TI - 3:4-benzxanthene. PMID- 21024263 TI - Rh antigens and antibodies in man. PMID- 21024264 TI - Incidence of the Rh factor in Indians. PMID- 21024265 TI - Mixed iodophile populations of the human colon and caecum. PMID- 21024267 TI - Influence of sodium thiocyanate on the development of the chick embryo. PMID- 21024266 TI - Adrenocorticotrophic activity in urine from pregnant women. PMID- 21024268 TI - Venereal disease in West Africa. PMID- 21024270 TI - Endocrine correlation in the embryonal development of the vertebrates. PMID- 21024269 TI - Protein structure in the light of analytical chemistry. PMID- 21024271 TI - Nutritional value of beer. PMID- 21024272 TI - Constitution of strychnine and the biogenetic relationship of strychnine and quinine. PMID- 21024273 TI - Antimalarial action of cinnoline derivatives. PMID- 21024274 TI - Antimalarial activity and toxicity of a metabolic derivative of quinine. PMID- 21024275 TI - Toadstools and mushrooms as a source of antibacterial substances active against Mycobacterium phlei and Bact. typhosum. PMID- 21024276 TI - Aphosphorosis in cattle in Offaly. PMID- 21024278 TI - A definition of plasticity. PMID- 21024277 TI - Physiological activity of a single follicle occurring in an aberrant baboon ovary. PMID- 21024279 TI - Chemical nature of salts from bones and teeth and of tricalcium phosphate precipitates. PMID- 21024280 TI - Antibacterial substances produced by bacteria and fungi. PMID- 21024284 TI - A reliable high vacuum gauge and control system. PMID- 21024285 TI - The stabilization of x-ray tube current and voltage. PMID- 21024286 TI - TUNING-FORK frequency standard. PMID- 21024287 TI - Catalysis in industry, biology, and medicine. PMID- 21024288 TI - Insect control for the Marines. PMID- 21024289 TI - The Army's war against malaria. PMID- 21024290 TI - Integration in science teaching. PMID- 21024291 TI - General semantics and the science of man. PMID- 21024292 TI - Sunburn protection, natural and artificial. PMID- 21024293 TI - Distamperoid virus interference in canine distemper. PMID- 21024294 TI - Availability of carotene from kale. PMID- 21024295 TI - The growth and distribution of murine encephalomyelitis virus in the developing chick embryo. PMID- 21024296 TI - Oral penicillin X. PMID- 21024297 TI - Penicillin production by a superior strain of mold. PMID- 21024298 TI - The evolution of oxygen from illuminated suspensions of frozen, dried, and homogenized chloroplasts. PMID- 21024299 TI - [There is no trace left of the rich museum of the history of medicine]. PMID- 21024300 TI - Production of penicillin X in submerged surface cultures. PMID- 21024301 TI - A low-resistance valve and indicating flowmeter for respiratory measurements. PMID- 21024302 TI - Degradation of streptomycin and the structure of streptidine and streptamine. PMID- 21024303 TI - Consultant articles. PMID- 21024304 TI - Some factors in the etiology of congenital malformations. PMID- 21024305 TI - A and B iso-immunization as a possible factor in the etiology of mental deficiency. PMID- 21024306 TI - A suggested definition of intelligence. PMID- 21024307 TI - The relationship between academic success and personality organization among subnormal girls. PMID- 21024308 TI - A comparison of social and intellectual levels of 100 high-grade adult mental defectives. PMID- 21024309 TI - Significance of psychological test results of exogenous and endogenous children. PMID- 21024310 TI - The use of the thematic apperception test with mentally deficient children; a study of high grade boys. PMID- 21024311 TI - Contribution of the child guidance clinic to the problem of mental deficiency. PMID- 21024313 TI - Post-war problems in guidance of the mentally subnormal. PMID- 21024312 TI - Certain relationships of crime and mental disorder. PMID- 21024314 TI - Mental defectives in military service and wartime industries. PMID- 21024315 TI - Study of feeble-minded wards employed in war industries. PMID- 21024316 TI - Identifying the slow-learning child. PMID- 21024317 TI - Manual assignments for the mentally deficient. PMID- 21024318 TI - The improvement of educational programs for the mentally deficient. PMID- 21024319 TI - Requisites for the further development of family care of mental patients. PMID- 21024320 TI - A study of psychological predisposition to the development of operational fatigue. PMID- 21024321 TI - The clinical psychologist in an Army hospital. PMID- 21024322 TI - The group factor in military psychiatry. PMID- 21024323 TI - A clinic's experience with the problems of the serviceman's wife. PMID- 21024325 TI - A study of the intelligence of institutionalized epileptics of the idiopathic type. PMID- 21024324 TI - Common syndromes in child psychiatry. PMID- 21024327 TI - The use of transference in case work treatment. PMID- 21024326 TI - Parental rejection of crippled children. PMID- 21024328 TI - Handling resistance in social case work. PMID- 21024329 TI - Protective case work in a family agency. PMID- 21024330 TI - Overt sympathy with the enemy in maladjusted children. PMID- 21024331 TI - A short form of the Wechsler-Bellevue Intelligence Test as applied to naval personnel. PMID- 21024332 TI - The effects of group psychotherapy on personality inventory scores. PMID- 21024333 TI - Strength through character. PMID- 21024334 TI - Program of the Veterans Administration for the physical and mental health of veterans. PMID- 21024335 TI - The freeing of intelligence. PMID- 21024336 TI - [Not Available]. PMID- 21024337 TI - [Not Available]. PMID- 21024338 TI - [Not Available]. PMID- 21024339 TI - [Not Available]. PMID- 21024340 TI - [Not Available]. PMID- 21024341 TI - [Not Available]. PMID- 21024342 TI - [Not Available]. PMID- 21024343 TI - [Not Available]. PMID- 21024344 TI - [Not Available]. PMID- 21024345 TI - [Not Available]. PMID- 21024346 TI - [Not Available]. PMID- 21024347 TI - Men who kill women. PMID- 21024348 TI - Ontogeny of bisexual differentiation in man. PMID- 21024349 TI - Psychotherapeutic problems in gynecological practice. PMID- 21024350 TI - Use of camphor dispersion in the convulsive therapy of schizophrenia. PMID- 21024351 TI - The role of the endocrine glands in emotional disturbances, crime and rehabilitation. PMID- 21024352 TI - Psychosomatic factors in hearing. PMID- 21024353 TI - The effect of disappointment on ego and super-ego formation in normal and depressive development. PMID- 21024354 TI - The danger neurotics dread most: loss of the basic fallacy. PMID- 21024355 TI - Masochistic motives in the literary and graphic art of Bruno Schulz. PMID- 21024356 TI - First contribution to the psycho-analysis and aesthetics of motion picture. PMID- 21024357 TI - The fear of post-orgastic emptiness. PMID- 21024358 TI - [Not Available]. PMID- 21024359 TI - [Not Available]. PMID- 21024360 TI - [Not Available]. PMID- 21024361 TI - [Not Available]. PMID- 21024362 TI - [Not Available]. PMID- 21024363 TI - [Not Available]. PMID- 21024364 TI - [Not Available]. PMID- 21024365 TI - [Not Available]. PMID- 21024366 TI - [Not Available]. PMID- 21024367 TI - [Not Available]. PMID- 21024368 TI - [Not Available]. PMID- 21024370 TI - [Not Available]. PMID- 21024369 TI - [Not Available]. PMID- 21024371 TI - [Not Available]. PMID- 21024372 TI - [Not Available]. PMID- 21024373 TI - [Not Available]. PMID- 21024374 TI - [Not Available]. PMID- 21024375 TI - [Not Available]. PMID- 21024376 TI - [Not Available]. PMID- 21024377 TI - [Not Available]. PMID- 21024378 TI - [Not Available]. PMID- 21024379 TI - [Not Available]. PMID- 21024380 TI - [Not Available]. PMID- 21024381 TI - [Not Available]. PMID- 21024382 TI - [Not Available]. PMID- 21024383 TI - [Not Available]. PMID- 21024384 TI - [Not Available]. PMID- 21024385 TI - Intravitreal injection of penicillin in a case of incipient abscess of the vitreous following extracapsular cataract extraction; perfect cure. PMID- 21024386 TI - [Not Available]. PMID- 21024387 TI - [Not Available]. PMID- 21024388 TI - [Not Available]. PMID- 21024389 TI - [Not Available]. PMID- 21024390 TI - [Not Available]. PMID- 21024391 TI - [Not Available]. PMID- 21024392 TI - [Not Available]. PMID- 21024394 TI - [Not Available]. PMID- 21024393 TI - [Not Available]. PMID- 21024395 TI - Cataracts. PMID- 21024396 TI - The partially seeing child in 1950. PMID- 21024397 TI - The one-eyed worker. PMID- 21024398 TI - Prevention of blindness activities in Brazil. PMID- 21024399 TI - The nerve-fibre bundle defect. PMID- 21024400 TI - Discussion on ocular psychoneuroses. PMID- 21024401 TI - Discussion on ocular psychoneuroses. PMID- 21024402 TI - Psychology in every-day ophthalmic practice. PMID- 21024403 TI - Functional disorders of the visual apparatus. PMID- 21024404 TI - Ocular psycho-neuroses of childhood. PMID- 21024405 TI - Artefact conjunctivitis. PMID- 21024406 TI - Ocular manifestations of psychoneurosis. PMID- 21024407 TI - Discussion on virus diseases of the eye. PMID- 21024408 TI - Ocular lesions in some systemic virus diseases. PMID- 21024409 TI - If epidemic kerato-conjunctivitis is a virus disease, is Herbert's bacillus of any pathological significance? PMID- 21024410 TI - Virus affections of the eye. PMID- 21024411 TI - Herpes zoster and varicella eruption. PMID- 21024412 TI - The distribution of the trachoma virus in human tissue. PMID- 21024413 TI - A sequel to the case of spontaneous cure of glioma of the retina, reported in the Transactions, 1937. PMID- 21024414 TI - Radon seeds in the treatment of glioma retinae. PMID- 21024415 TI - Concentric restriction of vision from unilateral cerebral lesions. PMID- 21024416 TI - Fractures of the orbit. PMID- 21024417 TI - Sphenoidal mucocele as a cause of the ophthalmoplegic migraine syndrome. PMID- 21024418 TI - Preventable blindness in war. PMID- 21024419 TI - Hyaline bodies in the intra-ocular fluids and tissues. PMID- 21024420 TI - The use of plastic materials for scleral wounds. PMID- 21024422 TI - Ophthalmic experiences in the East. PMID- 21024421 TI - The elastic tissue within the eye. PMID- 21024423 TI - Two cases of epicanthus treated by Spaeth's epicanthus operation. PMID- 21024424 TI - Two cases of bilateral ptosis and epicanthus treated by Lexer's ptosis and Blair's epicanthus operation. PMID- 21024425 TI - Hypotonia following contusion. PMID- 21024426 TI - Ocular paralysis following spinal anaesthesia. PMID- 21024427 TI - Paresis of the right superior oblique following an accident treated by operation. PMID- 21024428 TI - Paralysis of the left inferior oblique and left superior rectus treated by operation. PMID- 21024429 TI - Congenital paralysis of left internal rectus and inferior oblique treated by transplantation of superior oblique muscle. PMID- 21024431 TI - Ray cataracts. PMID- 21024430 TI - Report on two cases of uvecparotitis. PMID- 21024432 TI - Heat ray cataract. PMID- 21024433 TI - A note on the treatment of hypopyon ulcer. PMID- 21024434 TI - Retinal haemorrhage with vitreous clouding in young adults (Eales' disease). PMID- 21024435 TI - Operative treatment of glaucoma. PMID- 21024436 TI - Treatment of glaucoma. PMID- 21024437 TI - Treatment of glaucoma. PMID- 21024439 TI - Sympathetic ophthalmitis. PMID- 21024438 TI - A statistical inquiry into the incidence of phlyctenular disease in Dublin. PMID- 21024441 TI - Oto-rhino-laryngology in the Navy. PMID- 21024440 TI - The masking effect of sulphonamide when used in the treatment of acute otitis media. PMID- 21024442 TI - Ethmoidal epistaxis necessitating operation; case report. PMID- 21024443 TI - Gun blast and the use of moulded ear defenders. PMID- 21024444 TI - [Not Available]. PMID- 21024445 TI - [Not Available]. PMID- 21024446 TI - [Not Available]. PMID- 21024447 TI - [Not Available]. PMID- 21024448 TI - [Not Available]. PMID- 21024449 TI - [Not Available]. PMID- 21024450 TI - [Not Available]. PMID- 21024451 TI - [Not Available]. PMID- 21024452 TI - [Not Available]. PMID- 21024453 TI - [Not Available]. PMID- 21024454 TI - [Not Available]. PMID- 21024455 TI - [Not Available]. PMID- 21024456 TI - [Not Available]. PMID- 21024457 TI - [Not Available]. PMID- 21024459 TI - [Not Available]. PMID- 21024458 TI - [Not Available]. PMID- 21024460 TI - [Not Available]. PMID- 21024461 TI - [Not Available]. PMID- 21024462 TI - [Not Available]. PMID- 21024463 TI - [Not Available]. PMID- 21024464 TI - [Not Available]. PMID- 21024465 TI - [Not Available]. PMID- 21024466 TI - Contribution to treatment of chronic laryngitis in persons who use their voices professionally. PMID- 21024467 TI - [Not Available]. PMID- 21024468 TI - [Not Available]. PMID- 21024469 TI - [Not Available]. PMID- 21024470 TI - [Not Available]. PMID- 21024471 TI - [Not Available]. PMID- 21024472 TI - [Not Available]. PMID- 21024473 TI - [Not Available]. PMID- 21024474 TI - [Not Available]. PMID- 21024475 TI - [Not Available]. PMID- 21024476 TI - [Not Available]. PMID- 21024478 TI - [Not Available]. PMID- 21024477 TI - [Not Available]. PMID- 21024479 TI - [Not Available]. PMID- 21024480 TI - [Not Available]. PMID- 21024481 TI - [Not Available]. PMID- 21024482 TI - Observations on child welfare in Europe gleaned from attendance at the International Labor Conference, Paris, October 15-November 5, 1945. PMID- 21024483 TI - [Not Available]. PMID- 21024484 TI - [Not Available]. PMID- 21024485 TI - [Not Available]. PMID- 21024486 TI - Level of aspiration in relation to personality factors in adolescents. PMID- 21024487 TI - School absence due to sickness in the war years. PMID- 21024489 TI - Streptomycin. PMID- 21024488 TI - Traumatic head injuries in infants and children. PMID- 21024490 TI - Advances in immunization in pediatric practice. PMID- 21024491 TI - Lymphosarcoma. PMID- 21024492 TI - The assay of medicinal compounds having caffeine as a common ingredient. PMID- 21024493 TI - Methods of testing antibiotic substances and limitations involved. PMID- 21024494 TI - Some cardiac effects of isonipecaine (demerol). PMID- 21024495 TI - Investigations of the heavy metals test in the U.S. Pharmacopoeia XII. PMID- 21024497 TI - Separation of l-menthol from racemic menthol U.S.P. PMID- 21024496 TI - The influence of fertilizers on the growth and alkaloidal content of Hyoscyamus niger Linn. PMID- 21024498 TI - Aseptic filling of sterile solutions. PMID- 21024499 TI - [Not Available]. PMID- 21024500 TI - [Not Available]. PMID- 21024501 TI - [Not Available]. PMID- 21024502 TI - [Not Available]. PMID- 21024503 TI - [Not Available]. PMID- 21024504 TI - [Not Available]. PMID- 21024505 TI - [Not Available]. PMID- 21024506 TI - [Not Available]. PMID- 21024507 TI - [Not Available]. PMID- 21024508 TI - [Not Available]. PMID- 21024509 TI - [Not Available]. PMID- 21024510 TI - [Not Available]. PMID- 21024511 TI - [Not Available]. PMID- 21024512 TI - [Not Available]. PMID- 21024513 TI - [Not Available]. PMID- 21024515 TI - [Not Available]. PMID- 21024514 TI - [Not Available]. PMID- 21024516 TI - Studies in job evaluation; an analysis of point ratings for salary paid jobs in an industrial plant. PMID- 21024517 TI - A preliminary report on the Miami-Oxford curve-block series. PMID- 21024518 TI - A comparative study of three tests for color vision. PMID- 21024519 TI - Studies in the application of motor skills techniques to the vocational adjustment of the blind. PMID- 21024520 TI - The significance of verbal aptitude in the type of occupation pursued by illiterates. PMID- 21024521 TI - Readability of newspaper headlines printed in capitals and in lower case. PMID- 21024522 TI - Explorations in personality by the sentence completion method. PMID- 21024523 TI - Speech intelligibility under various degrees of anoxia. PMID- 21024524 TI - Description of a project in group therapy. PMID- 21024525 TI - Eye-movements during prolonged reading. PMID- 21024526 TI - The constancy of colored objects in colored illumination. PMID- 21024527 TI - The width of the basilar membrane in the guinea pig. PMID- 21024528 TI - The relation between frequency of blinking and effort expended in mental work. PMID- 21024529 TI - Genetic changes in semantic conditioning. PMID- 21024530 TI - Incidental learning and generality of set. PMID- 21024531 TI - The learning and retention of concepts; the influence of length of series; the origin of concepts. PMID- 21024532 TI - The psychokinetic effect: a review. PMID- 21024533 TI - GESP experiments with the free response method. PMID- 21024534 TI - A digest and discussion of some comments on Telepathy and clairvoyance reconsidered. PMID- 21024535 TI - Position effects in PK tests with 24 dice. PMID- 21024536 TI - The psychology of participation. PMID- 21024537 TI - An experiment with group methods in the selection of trainees for senior management positions. PMID- 21024538 TI - Staff transfers and promotions. PMID- 21024539 TI - The short personnel selection interview. PMID- 21024540 TI - [Not Available]. PMID- 21024541 TI - [Not Available]. PMID- 21024542 TI - [Not Available]. PMID- 21024543 TI - A protective service for promiscuous girls. PMID- 21024544 TI - [Not Available]. PMID- 21024545 TI - A method of making actuarial estimates for a compulsory health insurance system. PMID- 21024547 TI - Food poisoning. PMID- 21024546 TI - European health problems; U.N. R.R.A.'s part in controlling them. PMID- 21024548 TI - Bovine diseases communicable to man. PMID- 21024549 TI - The Education Act, 1944, and the handicapped child. PMID- 21024550 TI - Some foibles of sanitary engineering. PMID- 21024551 TI - Some problems of water supplies in rural areas at home and overseas. PMID- 21024552 TI - Building and staffing of a maternity hospital in war-time. PMID- 21024553 TI - MOTHERS having babies at younger ages. PMID- 21024554 TI - A statistical study of 500 psychopathic prisoners. PMID- 21024555 TI - A public health program for rural areas. PMID- 21024556 TI - Homologous serum jaundice; experimental inactivation of etiologic agent in serum by ultraviolet irradiation. PMID- 21024557 TI - Instructions for using ANTU as a poison for the common Norway rat. PMID- 21024558 TI - Results of roentgen treatment of leukemia. PMID- 21024559 TI - Hematological and clinical characteristics of leukemia. PMID- 21024560 TI - A roentgen study of chronic pulmonary coccidioidomycosis. PMID- 21024561 TI - The myelographic diagnosis of extramedullary cervical spinal cord tumors. PMID- 21024562 TI - The Ehlers-Danlos syndrome. PMID- 21024563 TI - A quantitative roentgenographic method for the determination of left auricular size; normal standards. PMID- 21024564 TI - Retrograde abdominal aortography. PMID- 21024565 TI - Right-sided aortic arch; case report. PMID- 21024566 TI - The supine projection in the diagnosis of lesions of the corpus and posterior wall of the stomach. PMID- 21024567 TI - The coagulogram as a critical indicator of irradiation effect; preliminary report based upon a seven year survey of the personnel of the Department of Radiology, Royal Victoria Hospital. PMID- 21024568 TI - The effect of roentgen therapy on experimental virus pneumonia; on feline virus pneumonia. PMID- 21024569 TI - The effect of roentgen therapy on experimental virus pneumonia; on pneumonia produced in white mice by swine influenza virus. PMID- 21024570 TI - Aerotitis and its prevention by the use of radium. PMID- 21024571 TI - Comments on the preparation and presentation of medical papers. PMID- 21024572 TI - Dosage control in interstitial radium therapy; symposium. PMID- 21024573 TI - Quantitative biological dose control in interstitial radium therapy. PMID- 21024574 TI - Chronic ulcerative oesophagitis with report of a case of ulcer in oesophageal varices. PMID- 21024575 TI - Stereoscopic screening. PMID- 21024576 TI - An investigation into the radiological appearances of the chests of workers engaged in the production of toxic gases. PMID- 21024577 TI - Graphite pneumoconiosis complicated by cavitation due to necrosis. PMID- 21024578 TI - Tactics and technique for urography. PMID- 21024580 TI - Tetratome attachment for layer radiography (tomography, etc.). PMID- 21024579 TI - Radiography in a faciomaxillary unit. PMID- 21024581 TI - A constant-area diaphragm. PMID- 21024582 TI - The Transylvania Medical Library; presidential address. PMID- 21024583 TI - Newer concepts in the treatment of the paralyzed patients due to war-time injuries of the spinal cord; outline of plan and statistical analysis. PMID- 21024584 TI - Newer concepts in the treatment of the paralyzed patient due to war-time injuries of the spine; neurosurgical complications. PMID- 21024585 TI - Methods of closure of decubitus ulcers in the paralyzed patient. PMID- 21024586 TI - Battle injuries of the arteries in World War II; an analysis of 2,471 cases. PMID- 21024587 TI - Traumatic arteriovenous fistula involving the abdominal aorta and the inferior vena cava. PMID- 21024588 TI - Cirsoid aneurysm of the scalp. PMID- 21024589 TI - The management of aneurysms of the lower extremities. PMID- 21024590 TI - Plastic surgery in World War I and in World War II. PMID- 21024591 TI - Use of cancellous bone in the repair of defects about the jaws. PMID- 21024593 TI - Fixation of tendons, ligaments and bone by Bunnell's pull-out wire suture. PMID- 21024592 TI - Muscle-flap transplant for the relief of painful monarticular arthritis (aseptic necrosis) of the hip. PMID- 21024595 TI - Dyschondroplasia. PMID- 21024594 TI - Muscle flap closure of cavity resulting from lung abscess. PMID- 21024596 TI - Traumatic osteomyelitis; the use of skin grafts. PMID- 21024597 TI - Repair of bony defects associated with osteomyelitis. PMID- 21024598 TI - Effects of an artificial ductus arteriosus on experimental cyanosis and anoxemia. PMID- 21024599 TI - Submucosal lipomas of the stomach; a review of the literature and report of a case associated with carcinoma. PMID- 21024600 TI - A basis for sympathectomy for cancer of the cervix uteri. PMID- 21024601 TI - Cutis graft in surgery; a review of results obtained, with comments on indications and technic and report of cases. PMID- 21024602 TI - Review of urologic surgery. PMID- 21024603 TI - PROGRESS in orthopedic surgery for 1944. PMID- 21024604 TI - [Not Available]. PMID- 21024605 TI - [Not Available]. PMID- 21024606 TI - [Not Available]. PMID- 21024607 TI - [Not Available]. PMID- 21024608 TI - [Not Available]. PMID- 21024609 TI - [Not Available]. PMID- 21024611 TI - [Not Available]. PMID- 21024610 TI - [Not Available]. PMID- 21024612 TI - [Not Available]. PMID- 21024613 TI - [Not Available]. PMID- 21024614 TI - [Not Available]. PMID- 21024615 TI - [Not Available]. PMID- 21024616 TI - [Not Available]. PMID- 21024617 TI - [Not Available]. PMID- 21024618 TI - [Not Available]. PMID- 21024619 TI - [Not Available]. PMID- 21024620 TI - [Not Available]. PMID- 21024621 TI - [Not Available]. PMID- 21024622 TI - [Not Available]. PMID- 21024623 TI - [Not Available]. PMID- 21024624 TI - Hernia of the lung. PMID- 21024625 TI - Intrapericardial approach to the lung root in the treatment of bronchial carcinoma by dissection pneumonectomy. PMID- 21024626 TI - Treatment of pulmonary actinomycosis with a report of seven arrested cases. PMID- 21024627 TI - Production of mucus in primary neoplasms of the lung. PMID- 21024629 TI - A thoracic support. PMID- 21024628 TI - Lipoma of the bronchus: discussion of benign neoplasms and report of a case of endobronchial lipoma. PMID- 21024630 TI - [Not Available]. PMID- 21024631 TI - [Not Available]. PMID- 21024632 TI - [Not Available]. PMID- 21024633 TI - [Not Available]. PMID- 21024634 TI - [Not Available]. PMID- 21024635 TI - [Not Available]. PMID- 21024636 TI - [Not Available]. PMID- 21024637 TI - [Not Available]. PMID- 21024638 TI - [Not Available]. PMID- 21024639 TI - [Not Available]. PMID- 21024640 TI - [Not Available]. PMID- 21024641 TI - [Not Available]. PMID- 21024642 TI - [Not Available]. PMID- 21024643 TI - [Not Available]. PMID- 21024644 TI - [Not Available]. PMID- 21024645 TI - [Not Available]. PMID- 21024646 TI - [Not Available]. PMID- 21024647 TI - [Not Available]. PMID- 21024648 TI - [Not Available]. PMID- 21024649 TI - [Not Available]. PMID- 21024650 TI - [Not Available]. PMID- 21024651 TI - [Not Available]. PMID- 21024652 TI - [Not Available]. PMID- 21024653 TI - [Not Available]. PMID- 21024654 TI - [Not Available]. PMID- 21024655 TI - [Not Available]. PMID- 21024656 TI - [Not Available]. PMID- 21024657 TI - [Not Available]. PMID- 21024658 TI - [Not Available]. PMID- 21024659 TI - [Not Available]. PMID- 21024660 TI - [Not Available]. PMID- 21024661 TI - [Not Available]. PMID- 21024662 TI - [Not Available]. PMID- 21024663 TI - Differential diagnosis between ruptured lumbar intervertebral disk and certain diseases of the spinal and peripheral nervous systems. PMID- 21024664 TI - The diagnosis of lesions of the mediastina. PMID- 21024665 TI - The importance of bronchoscopy in planning the treatment of pulmonary lesions. PMID- 21024666 TI - The blood picture in patients with primary cancer of the lung. PMID- 21024667 TI - The radiological diagnosis of certain diseases of the lower esophagus. PMID- 21024669 TI - Angiography, an evaluation of its usefulness. PMID- 21024668 TI - The diagnosis of tumors of the breast. PMID- 21024670 TI - Congenital arteriovenous aneurysms or fistulas. PMID- 21024671 TI - Aneurysm of the abdominal aorta. PMID- 21024672 TI - Diagnosis of perinephric abscess. PMID- 21024673 TI - Pheochromocytoma of the adrenal gland; a report of two cases with operative removal of the tumor. PMID- 21024674 TI - Intestinal obstruction. PMID- 21024675 TI - Diverticulitis of the colon. PMID- 21024676 TI - Perforating wounds of the rectum. PMID- 21024678 TI - The diagnosis of neoplasms of bone. PMID- 21024677 TI - Surgical diagnosis of acute injuries of the knee joint. PMID- 21024679 TI - Indications for the Syme amputation. PMID- 21024680 TI - The diagnosis of peripheral nerve lesions. PMID- 21024681 TI - Calculus formation in the bedrest patient. PMID- 21024682 TI - Cesarean section: its uses and abuses. PMID- 21024683 TI - Technic of thyroidectomy; a satisfactory method for the young surgeon. PMID- 21024684 TI - Bilateral paralysis of the abductor muscles of the larynx; arytenoidectomy. PMID- 21024685 TI - The surgical treatment of chronic constrictive pericarditis. PMID- 21024686 TI - The problem of parotid tumors. PMID- 21024687 TI - Concerning amputations. PMID- 21024688 TI - Plastic operations for hydronephrosis. PMID- 21024689 TI - A discussion of controversial points in amputation surgery. PMID- 21024690 TI - Cancer of the cervix; a new technique for interstitial implantation of radium into the parametrium. PMID- 21024692 TI - Pancreatic heterotopia; review of the literature and report of 41 authenticated surgical cases, of which 25 were clinically significant. PMID- 21024691 TI - Correction of esophageal atresia and tracheo-esophageal fistula by closure of fistula and oblique anastomosis of esophageal segments. PMID- 21024694 TI - Postcaval ureter, with description of a new operation for its correction. PMID- 21024693 TI - Secondary suture of war wounds; a study of methods and results in an overseas general hospital. PMID- 21024695 TI - Topical penicillin treatment of established infection in compound fracture wounds. PMID- 21024696 TI - Is the biopsy of neoplasms dangerous? PMID- 21024697 TI - Chronic osteomyelitis complicating war compound fractures; an evaluation of 125 patients treated by early secondary closure. PMID- 21024698 TI - Persistence of the vitelline (omphalomesenteric) artery as a clinical problem. PMID- 21024699 TI - A study of the effect of prophylactic oral sulfadiazine upon infection in soft tissue war wounds closed secondarily. PMID- 21024700 TI - The pelvic autonomic nerves in the male. PMID- 21024701 TI - Studies on exopthalmos produced by thyrotropic hormone; changes induced in various tissues and organs (including the orbit) by thyrotropic hormone and their relationship to exophthalmos. PMID- 21024702 TI - The use of compression in the treatment of injuries. PMID- 21024703 TI - Penetrating cranial wounds; a summary of methods used in management; collective review. PMID- 21024704 TI - Physical medicine in surgical convalescence. PMID- 21024705 TI - The expanding field of physical medicine. PMID- 21024706 TI - Studies on neuro-muscular dysfunction; neostigmine therapy of acute and chronic backache. PMID- 21024707 TI - Treatment of sciatica with alternating current. PMID- 21024709 TI - TYPING and cross-matching of blood. PMID- 21024710 TI - Fluid administration through long bones. PMID- 21024708 TI - Penicillin combined with fever therapy; a preliminary report of twenty cases of early syphilis. PMID- 21024711 TI - Free plasma service in North Dakota. PMID- 21024712 TI - [Not Available]. PMID- 21024713 TI - [Not Available]. PMID- 21024714 TI - PERTUSSIS immunization. PMID- 21024715 TI - MALNUTRITION in children. PMID- 21024716 TI - [Not Available]. PMID- 21024717 TI - [Not Available]. PMID- 21024718 TI - [Not Available]. PMID- 21024719 TI - [Not Available]. PMID- 21024720 TI - [Not Available]. PMID- 21024721 TI - [Not Available]. PMID- 21024722 TI - [Not Available]. PMID- 21024723 TI - [Not Available]. PMID- 21024724 TI - [Not Available]. PMID- 21024725 TI - [Not Available]. PMID- 21024726 TI - [Not Available]. PMID- 21024727 TI - [Not Available]. PMID- 21024728 TI - [Not Available]. PMID- 21024729 TI - Plasma viscosity in pulmonary tuberculosis and other diseases. PMID- 21024730 TI - The course of the fever curve in exudative pleurisy with special regard to the effect of sanocrysin. PMID- 21024731 TI - [Not Available]. PMID- 21024732 TI - Tubercle bacillus allergy in tuberculin anergetics. PMID- 21024733 TI - Primary pulmonary tuberculosis with erythema nodosum in connection with B.C.G. vaccination. PMID- 21024734 TI - Mixed infection in tuberculosis; with special reference to post mortem bacteriologic studies in two exanthema cases. PMID- 21024735 TI - Some noteworthy points of view regarding the choice of method in the surgical treatment of pulmonary tuberculosis. PMID- 21024736 TI - Occurrence and manifestations of tuberculosis in Iceland. PMID- 21024737 TI - Millennium of control of tuberculosis. PMID- 21024738 TI - [Not Available]. PMID- 21024739 TI - [Not Available]. PMID- 21024740 TI - [Not Available]. PMID- 21024741 TI - [Not Available]. PMID- 21024742 TI - [Not Available]. PMID- 21024743 TI - [Not Available]. PMID- 21024744 TI - [Not Available]. PMID- 21024745 TI - [Not Available]. PMID- 21024746 TI - [Not Available]. PMID- 21024747 TI - [Not Available]. PMID- 21024748 TI - Penicillin in the treatment of venereal diseases. PMID- 21024749 TI - Post-arsenic jaundice and related types of hepatitis. PMID- 21024750 TI - The revised reports and forms of the Venereal Disease Division. PMID- 21024751 TI - Blood testing and treatment program in Jefferson County, Alabama. PMID- 21024752 TI - Studies on chancroid; Ducrey skin reactions in Negro hospital patients. PMID- 21024753 TI - Changes in the equine larynx associated with laryngeal hemiplegia. PMID- 21024754 TI - A contagious disease of cattle associated with Leptospira. PMID- 21024755 TI - Observations on the prophylactic and curative value of sulfaguanidine in swing coccidiosis. PMID- 21024756 TI - Experiments on the pathogenicity of hookworm (Bunostomum trigonocephalum) infections in lambs fed an adequate diet. PMID- 21024757 TI - The transmission of lymphomatosis in the fowl. PMID- 21024759 TI - Veterinary service in a zoo. PMID- 21024758 TI - Rabies and its control. PMID- 21024760 TI - Efficacy of various agents for delaying absorption of penicillin. PMID- 21024761 TI - Field experience in public health for veterinarians. PMID- 21024762 TI - DDT: a review; with special reference to veterinary medicine. PMID- 21024763 TI - Mummified fetus. PMID- 21024764 TI - A method for the aseptic bleeding of animals. PMID- 21024765 TI - TETANUS anatoxin, the life saver. PMID- 21024766 TI - Digital tenotomy in foxes. PMID- 21024767 TI - The treatment of enteritis with sulfathalidine. PMID- 21024768 TI - Spirochetosis in turkeys (a preliminary report). PMID- 21024769 TI - Note on Salmonella in poultry products. PMID- 21024770 TI - Lymphocytoma (leucemia) in a cow; report of case. PMID- 21024771 TI - VITAMIN K. PMID- 21024772 TI - PLAGUES from the Orient and elsewhere. PMID- 21024773 TI - Mortality in young pigs; availability of iron in relation to anaemia. PMID- 21024774 TI - The use of the stomach tube. PMID- 21024775 TI - The problem of the non-specific serological reaction. PMID- 21024776 TI - Notes on pleuropneumonia. PMID- 21024777 TI - Progeny testing to increase viability. PMID- 21024778 TI - Variations in vital factors in small animals. PMID- 21024779 TI - The transmission of immunity to infectious diseases from mother to offspring. PMID- 21024780 TI - Hypoderma lineata, an erratic parasite in the cat. PMID- 21024781 TI - Critical anthelmintic tests in cattle. PMID- 21024782 TI - Chemotherapy of Erysipelothrix rhusiopathiae infections in mice. PMID- 21024783 TI - A case of multiple arthritis in a thoroughbred. PMID- 21024784 TI - Incidence of pathogenic bacteria in market milk of Cairo. PMID- 21024785 TI - VETERINARY CORPS develops a new rinderpest vaccine. PMID- 21024786 TI - Effects of chorionic gonadotropin on cystic ovaries in the cow. PMID- 21024787 TI - The veterinary practitioner's contribution to health. PMID- 21024788 TI - Diagnosing lightning stroke. PMID- 21024789 TI - Reminiscences. PMID- 21024790 TI - Chemical caponization of cockerels. PMID- 21024791 TI - Hypoderma lineata larvae in wall of esophagus. PMID- 21024792 TI - Hemangioma of the spleen (splenic tumor). PMID- 21024793 TI - Discouraging dystocias relieved by upward traction. PMID- 21024794 TI - Clinical note on treatment of cow pox. PMID- 21024795 TI - A new colloidal iodine for therapeutic use. PMID- 21024796 TI - Growth hormone in rickets of a dog. PMID- 21024797 TI - The development of the pharynx of the guinea pig with special emphasis on the morphogenesis of the thymus. PMID- 21024798 TI - Histochemical reactions of the placenta of the pig. PMID- 21024799 TI - The basophilic bodies in hepatic cells. PMID- 21024800 TI - Sectioning for the electron microscope accomplished by the high speed microtome. PMID- 21024801 TI - Progress in the standardization of stains; recent advances. PMID- 21024802 TI - Comparative absorption readings obtained with spectrophotometers of various types. PMID- 21024803 TI - The differentiation of placoid, ctenoid and cycloid scales by means of alizarin red S. PMID- 21024804 TI - The Bodian technic and the mosquito nervous system. PMID- 21024805 TI - Improved fixation in vitally stained methylene blue preparations. PMID- 21024806 TI - A simplified stain for hemoglobin in tissues or smears using patent blue. PMID- 21024807 TI - A simplified method of preparation of di-ammine-silver hydroxide for reticulum impregnation; comments on the nature of the so-called sensitization before impregnation. PMID- 21024808 TI - The use of clarite in preparing whole microscopic mounts. PMID- 21024809 TI - Sterile milk for background in capsule staining. PMID- 21024810 TI - Sulfa drugs to control American foulbrood. PMID- 21024811 TI - Influence of soil minerals on insects. PMID- 21024812 TI - Investigations at the Henry R. Carter Memorial Laboratory of the United States Public Health Service. PMID- 21024813 TI - DDT to control bugs that cause deformed peaches. PMID- 21024814 TI - DDT and its effect on fish and wildlife. PMID- 21024815 TI - DDT emulsion applied to rice-field water to control mosquitoes. PMID- 21024816 TI - DDT residual-type sprays as affected by light. PMID- 21024817 TI - DDT to control household and stored grain insects. PMID- 21024818 TI - DDT to control hornflies and Gulf Coast ticks on range cattle in Florida. PMID- 21024819 TI - DDT for the control of the horn fly in Kansas. PMID- 21024820 TI - Azobenzene as an acaricide and insecticide. PMID- 21024821 TI - Mosquito collections at Army installations in the Fourth Service Command, 1943. PMID- 21024822 TI - DDT and hornfly populations. PMID- 21024823 TI - DDT to control the winter horse tick. PMID- 21024824 TI - Antagonism and antibiotics. PMID- 21024825 TI - Sex hormones and their relationships. PMID- 21024826 TI - Confusion thrice confounded. Nomenclature. PMID- 21024827 TI - [Not Available]. PMID- 21024828 TI - [Not Available]. PMID- 21024829 TI - [Not Available]. PMID- 21024830 TI - [Not Available]. PMID- 21024831 TI - Radium. PMID- 21024832 TI - Some cultural and cytological characteristics of human tumors in vitro. PMID- 21024833 TI - Potassium and calcium content of gastric carcinoma. PMID- 21024834 TI - Potassium and calcium content of carcinomas and papillomas of the colon. PMID- 21024835 TI - Relationship of the inherited susceptibility and the inherited hormonal influence in the development of mammary cancer in mice. PMID- 21024836 TI - A comparative morphological study of the mammary glands with reference to the known factors influencing the development of mammary carcinoma in mice. PMID- 21024838 TI - A comparative study of the ovaries of virgin mice of the dba and C57 black strains. PMID- 21024837 TI - Methylcholanthrene squamous cell carcinoma of the rat prostate with skeletal metastases, and failure of the rat liver to respond to the carcinogen. PMID- 21024839 TI - Factors influencing the stability of a filtrable agent of chicken leukosis and sarcoma. PMID- 21024840 TI - Use of the phlebomanometer; normal venous pressure values and a study of certain clinical aspects of venous hypertension in man. PMID- 21024841 TI - Hemodynamics of acute hemorrhage in man. PMID- 21024842 TI - The circulation in penetrating wounds of the chest; a study by the method of right heart catheterization. PMID- 21024843 TI - Pericardial tamponade from stab wound of the heart and pericardial effusion or empyema; a study utilizing the method of right heart catheterization. PMID- 21024844 TI - The effects of malaria on the heart. PMID- 21024845 TI - Further observations on the use of mercupurin administered orally. PMID- 21024846 TI - Massive left auricle with special reference to its etiology and mechanism; report of a case. PMID- 21024847 TI - The effect of certain drugs upon the cardiotoxic lesions of digitalis in the dog. PMID- 21024848 TI - Thromboplastic properties of some mercurial diuretics. PMID- 21024849 TI - An analysis of the time relationships within the cardiac cycle in electrocardiograms of normal men; the duration of the T-P interval and its relationship to the cycle length (R-R interval). PMID- 21024850 TI - An analysis of the time relationships within the cardiac cycle in electrocardiograms of normal men; the duration of the P-R interval and its relationship to the cycle length (R-R interval). PMID- 21024851 TI - The effect of change of position of the arm upon blood pressure. PMID- 21024852 TI - Electrocardiographic changes in scrub typhus fever. PMID- 21024853 TI - Persistent right aortic arch with atresia of the entire main pulmonary artery. PMID- 21024854 TI - Primary, massive calcification with ossification of the myocardium. PMID- 21024855 TI - Multiple disturbances of rhythm and conduction and unusual auricular T wave in a case of myocardial infarction. PMID- 21024856 TI - Transient bundle branch block associated with tachycardia. PMID- 21024857 TI - The determination of theobromine in cocoa residues; an examination of the Wadsworth method. PMID- 21024858 TI - A fluorimetric method for the estimation of riboflavine in egg white and egg yolk. PMID- 21024859 TI - An absorptiometric method for the determination of inorganic fluorides in organic products. PMID- 21024860 TI - The titration of microgram quantities of fluorides. PMID- 21024861 TI - The surface tension of slightly soluble fatty acids. PMID- 21024862 TI - Synthesis of some analogues of 1,1-bis-(p-chlorophenyl)-2,2,2-trichloroethane (DDT); three fluorine analogues. PMID- 21024863 TI - An automatic burette for the delivery of gas at constant pressure. PMID- 21024864 TI - Oxidation of lubricating oils. PMID- 21024865 TI - The synthesis of aromatic aldehydes. PMID- 21024866 TI - Metabolite antagonists. PMID- 21024867 TI - Synthetic estrogenic compounds; trialkyl derivatives of 1,3-di-(p-hydroxyphenyl) propane; benzestrol. PMID- 21024868 TI - Antibacterial action of an oxidation product of sulfanilamide. PMID- 21024869 TI - Studies in the synthesis of the antirachitic vitamins; 5-androstenol-3 and its partial dehydrogenation with benzoquinone. PMID- 21024870 TI - The ultraviolet absorption spectra of allyl and propenyl substituted derivatives of diethylstilbestrol and hexestrol. PMID- 21024872 TI - Monolayers of B-lactoglobulin; film molecular weight. PMID- 21024871 TI - Osmotic pressure of B-lactoglobulin solutions. PMID- 21024873 TI - Mixed monolayers of B-lactoglobulin and lauryl sulfate. PMID- 21024874 TI - Quaternary ammonium salts as germicides; non-acylated quaternary ammonium salts derived from aliphatic amines. PMID- 21024875 TI - Quaternary ammonium salts as germicides; acetoxy and carbethoxy derivatives of aliphatic quaternary ammonium salts. PMID- 21024876 TI - Quaternary ammonium salts as germicides; quaternary ammonium slats derived from cyclic amines. PMID- 21024877 TI - The papilionaceous alkaloids; Lupinus macounii, Rydb. PMID- 21024878 TI - Suflathiourea. PMID- 21024879 TI - Alkyl derivatives of sulfaguanidine. PMID- 21024880 TI - An isomer of thiamin. PMID- 21024881 TI - Streptomyces antibiotics; isolation of streptothricin. PMID- 21024882 TI - Streptomyces antibiotics; the structure of streptidine. PMID- 21024883 TI - Two 6-beta-hydroxyethoxy-8-diethylaminoalkylaminoquinolines. PMID- 21024884 TI - L-fructose. PMID- 21024885 TI - An instrument for determining the partial pressure of oxygen in a gas. PMID- 21024886 TI - The synthesis of homodesthiobiotin and related compounds. PMID- 21024887 TI - The microbiological synthesis of riboflavin; a theory concerning its inhibition. PMID- 21024888 TI - Pressor amines containing nuclear chlorine and fluorine. PMID- 21024889 TI - Cyclopropane derivatives; the electric moments of some alicyclic compounds. PMID- 21024890 TI - The alkaline hydrolysis of fluorenone-spiro-hydantoin. PMID- 21024891 TI - Optical and crystallographic properties of lysozyme chloride. PMID- 21024892 TI - The peptic digestion of human gamma globulin. PMID- 21024893 TI - The preparation and polymerization of the six nuclear isomeric dichlorostyrenes. PMID- 21024894 TI - Some quaternary ammonium salts of heterocyclic bases. PMID- 21024895 TI - The reaction of acetophenone with thiourea and oxidizing agents. PMID- 21024896 TI - The polymerization of p-chlorostyrene in the presence of polymethylacrylate. PMID- 21024897 TI - Synthesis of lysine anhydride. PMID- 21024898 TI - Alkylation of amines; N,N-dialkylation of nuclear substituted anilines. PMID- 21024899 TI - Ultraviolet absorption spectra of organic molecules; mechanical interference of substituent groups with resonance configurations. PMID- 21024900 TI - Salts and esters of hydroxylamine-O-sulfonic acid. PMID- 21024901 TI - Anils as open models of a modified atebrin. PMID- 21024902 TI - A convenient small osmometer. PMID- 21024903 TI - Fractionation of cellulose. PMID- 21024904 TI - Studies on the metabolism of brain suspensions; respiration at low oxygen tension. PMID- 21024905 TI - Studies on the metabolism of brain suspensions; anaerobic glycolysis. PMID- 21024906 TI - Infra-red absorption spectra of steroids; androgens and related steroids. PMID- 21024907 TI - A chick growth factor in cow manure; its non-identity with chick growth factors previously described. PMID- 21024908 TI - A chick growth factor in cow manure; the preparation of concentrates and the properties of the factor. PMID- 21024909 TI - Carbohydrate metabolism in the ascorbic acid-deficient guinea pig under normal and anoxic conditions. PMID- 21024910 TI - The effect of voluntary overbreathing on the electrolyte equilibrium of arterial blood in man. PMID- 21024911 TI - Notes on the determination and distribution of sodium and potassium in cells and serum of normal human blood. PMID- 21024912 TI - A simple method of preparation of colloidal ferrous iron for intravenous administration. PMID- 21024913 TI - The assay of animal tissues for respiratory enzymes; cell structure in relation to fatty acid oxidation. PMID- 21024914 TI - The Lactobacillus casei factors in the nutrition of the chick. PMID- 21024915 TI - The replacement of vitamin A1 by vitamin A2 in the retina of the rat. PMID- 21024916 TI - The synthesis of potential antimalarials; derivatives of pantoyltaurine. PMID- 21024917 TI - Studies on choline acetylase; the formation of acetylcholine in the nerve axon. PMID- 21024918 TI - Reversal of the action of phenyl pantothenone by certain amino acids. PMID- 21024919 TI - The ribonucleinase of the soy bean; isolation of the enzyme. PMID- 21024920 TI - An improved medium for microbiological assays with Lactobacillus casei. PMID- 21024921 TI - Determination of polysaccharide in serum. PMID- 21024922 TI - Preparation and properties of Plasmodium lophurae separated from the red cells of duck blood by means of saponin. PMID- 21024923 TI - Atabrine (quinacrine) inhibition of glucose oxidation in parasites initially depleted of substrate; reversal by adenylic acid. PMID- 21024924 TI - Flavoenzyme catalysis; inhibition of d-amino acid oxidase by competition with flavin-adenine-dinucleotide of atabrine (quinacrine); quinine, and certain other compounds. PMID- 21024925 TI - A crystalline protein with beta-amylase activity, prepared from sweet potatoes. PMID- 21024926 TI - The action of metmyoglobin, oxygen, and manganese on oxalacetic acid. PMID- 21024927 TI - The aerobic glycolysis of avian red blood cells and its control by intracellular ions in physiological concentrations. PMID- 21024928 TI - Solubility and melting point as functions of particle size. PMID- 21024929 TI - Effect of salts on the viscosity of pectinic acid solutions. PMID- 21024930 TI - The mechanism of the hydrogen-oxygen reaction; the third explosion limit. PMID- 21024931 TI - The mechanism of the hydrogen-oxygen reaction; the reaction occurring between the second and third explosion limits. PMID- 21024932 TI - The mechanism of the hydrogen-oxygen reaction; the influence of salts. PMID- 21024933 TI - The ionization of helium by neutral helium atoms. PMID- 21024934 TI - Dielectric properties of dipolar solids. PMID- 21024935 TI - Theory of the rheological properties of dispersions. PMID- 21024936 TI - The dissociation constants of the carboxyl and hydroxyl groups in some insoluble and sol-forming polysaccharides. PMID- 21024937 TI - Structure and thermal properties of crystals; the role of hydrogen bonds in Rochelle salt. PMID- 21024938 TI - Changing the occlusal level and a new method of retention. PMID- 21024939 TI - Orthodontics; its objectives, past and present. PMID- 21024940 TI - Indications for the extraction of teeth in orthodontic procedure. PMID- 21024941 TI - Fundamental principles and expedient compromises in orthodontic procedures. PMID- 21024942 TI - Anatomical and clinical problems involved where extraction is indicated in orthodontic treatment. PMID- 21024943 TI - Does scientific investigation support the extraction of teeth in orthodontic therapy? PMID- 21024944 TI - Studies on the rate and amount of eruption of certain human teeth. PMID- 21024945 TI - Heredity and variations in the dentofacial complex. PMID- 21024946 TI - Heredity as a guide in dentofacial orthopedics. PMID- 21024947 TI - Forsyth orthodontic survey of untreated cases. PMID- 21024948 TI - Phases of maxillofacial surgery of interest to the orthodontist. PMID- 21024949 TI - Effect of the Wagner Bill (S. 1161) upon the dental profession, the dentist, and the individual. PMID- 21024950 TI - Experimental depression of teeth. PMID- 21024951 TI - Variation of mandibular incisor axis in adult normal occlusion. PMID- 21024952 TI - Control of mandibular fragments by external fixation. PMID- 21024953 TI - Gum hyperplasia due to epanutin. PMID- 21024954 TI - A case of oral myiasis. PMID- 21024956 TI - Dry socket. PMID- 21024955 TI - The dentist's contribution to the diagnosis and treatment of cancer. PMID- 21024957 TI - Should this case be treated orthodontically? PMID- 21024958 TI - Allergic reactions to denture bases. PMID- 21024959 TI - Desiccation and sterilization of root canals by electrosurgery. PMID- 21024960 TI - A technique for full impressions using alginates or colloids. PMID- 21024961 TI - Emergency tracheotomy. PMID- 21024962 TI - A controlled correctable, and physiologically tolerable impression technique. PMID- 21024964 TI - Nutritional requirements, with special reference to the functioning of the teeth. PMID- 21024963 TI - What dentistry and dentists have accomplished. PMID- 21024965 TI - Pain control; the invaluable factor. PMID- 21024966 TI - A self-contained splint unit for fractures of the bones of the jaw and face. PMID- 21024967 TI - The laws of physics and engineering applied to dentistry. PMID- 21024968 TI - Dental caries inhibited by fluoride-vitamin tablets. PMID- 21024970 TI - Social security and the dental profession. PMID- 21024969 TI - An acrylic dowel crown with an attached gold inlay. PMID- 21024971 TI - Modified fixation appliances for controlling jaw fractures. PMID- 21024972 TI - Non-mutilating technic for moving impacted teeth. PMID- 21024973 TI - Recent advances in chemotherapy in oral surgery. PMID- 21024974 TI - Plastic artificial eye prosthesis. PMID- 21024975 TI - [Not Available]. PMID- 21024976 TI - [Not Available]. PMID- 21024977 TI - [Not Available]. PMID- 21024978 TI - [Not Available]. PMID- 21024979 TI - [Not Available]. PMID- 21024980 TI - [Not Available]. PMID- 21024981 TI - [Not Available]. PMID- 21024982 TI - Ethyl chloride as an anesthetic agent in minor dental surgery for children. PMID- 21024983 TI - The effect of cerophyl on the L. acidophilus of the oral cavity. PMID- 21024984 TI - Child psychology that pays. PMID- 21024985 TI - Penicillin in oral and maxillo-facial surgery. PMID- 21024987 TI - Interception of malocclusion. PMID- 21024986 TI - The physical forces or phenomena utilized in the retention of dentures. PMID- 21024988 TI - Fractures of the jaw. PMID- 21024989 TI - The tooth, the pulp, and the child. PMID- 21024990 TI - Discolorations of the oral mucous membrane by metallic foreign bodies. PMID- 21024991 TI - Periodontia case recording. PMID- 21024992 TI - The occlusal factor in periodontal disease. PMID- 21024993 TI - Newer concepts of caries prevention. PMID- 21024995 TI - The position of malocclusion in the cycle of dental disease. PMID- 21024994 TI - Root canal therapy for deciduous teeth. PMID- 21024996 TI - The use of barbiturates in dentistry. PMID- 21024997 TI - Intra-oral technique of the mandibular nerve block. PMID- 21024998 TI - Bone infection for painless dentistry. PMID- 21024999 TI - Trends in dental education. PMID- 21025000 TI - Trends affecting the future of dental education. PMID- 21025001 TI - The relationship of the dentist to neurotic psychological types. PMID- 21025002 TI - The dawn of modern anaesthesia. PMID- 21025003 TI - Enamel hypoplasia and oral disease. PMID- 21025005 TI - The private practitioner's role. PMID- 21025004 TI - The dental health problem in Minnesota. PMID- 21025006 TI - A practical school dental program. PMID- 21025007 TI - The role of genetics in orthodon tia. PMID- 21025008 TI - Dental health program in the District of Columbia. PMID- 21025009 TI - Treatment of pulpless teeth with penicillin points. PMID- 21025010 TI - [Not Available]. PMID- 21025011 TI - [Not Available]. PMID- 21025012 TI - [Not Available]. PMID- 21025013 TI - [Not Available]. PMID- 21025014 TI - [Not Available]. PMID- 21025015 TI - Dental disease as a fundamental problem. PMID- 21025016 TI - Some aspects of dental conditions involving the nasal sinuses. PMID- 21025017 TI - Highlights in the origin of Tufts College Dental School. PMID- 21025018 TI - The relationship between periodontal disease and caries. PMID- 21025019 TI - The relationship between hypopituitarism and the teeth. PMID- 21025020 TI - Dento-liability of the permanent dentition. PMID- 21025021 TI - Agents used in bleaching teeth. PMID- 21025023 TI - Hypoplasia of the deciduous dentition; report of a case. PMID- 21025022 TI - Direct polyacrylic restorations. PMID- 21025024 TI - [Not Available]. PMID- 21025025 TI - [Not Available]. PMID- 21025026 TI - [Not Available]. PMID- 21025027 TI - [Not Available]. PMID- 21025028 TI - [Not Available]. PMID- 21025029 TI - [Not Available]. PMID- 21025030 TI - [Not Available]. PMID- 21025031 TI - [Not Available]. PMID- 21025032 TI - [Not Available]. PMID- 21025033 TI - [Not Available]. PMID- 21025034 TI - [Not Available]. PMID- 21025035 TI - [Not Available]. PMID- 21025036 TI - [Not Available]. PMID- 21025037 TI - [Not Available]. PMID- 21025038 TI - [Not Available]. PMID- 21025039 TI - [Not Available]. PMID- 21025040 TI - [Not Available]. PMID- 21025041 TI - [Not Available]. PMID- 21025042 TI - [Not Available]. PMID- 21025043 TI - [Not Available]. PMID- 21025044 TI - [Not Available]. PMID- 21025045 TI - [Not Available]. PMID- 21025046 TI - [Not Available]. PMID- 21025047 TI - [Not Available]. PMID- 21025048 TI - Gastric aspiration culture and the control of tuberculosis. PMID- 21025049 TI - Admission hematology. PMID- 21025050 TI - Clinical evaluation of liver function tests. PMID- 21025051 TI - CLINICAL use of folic acid. PMID- 21025052 TI - Dried whole egg powder; accelerated storage tests to assess the effect of heat treatment, moisture content, and materials on the quality of dried sugar-egg mixtures. PMID- 21025053 TI - Liquid and frozen egg; methods of determining solids content of liquid and frozen egg. PMID- 21025054 TI - Protein hydrolysates; flavor ingredients for foods. PMID- 21025055 TI - Ascorbic acid content of the mango in relation to variety. PMID- 21025056 TI - Fermentation of coffee. PMID- 21025057 TI - Riboflavin content of tropical foods. PMID- 21025058 TI - Studies on vitamin content of canned pineapple. PMID- 21025059 TI - Vitamin P content of vegetables as influenced by chemical treatment. PMID- 21025060 TI - Ascorbic acid content of cabbage salads. PMID- 21025061 TI - Influence of chemical properties of soil on production of vitamin C in leaves of rye. PMID- 21025062 TI - Nutritive value of fish from Michigan waters; nicotinic acid of lake herring, carp, common suckers, and burbot. PMID- 21025063 TI - High protein diets in therapy of Rocky Mountain spotted fever. PMID- 21025064 TI - The dietary management of diabetes mellitus. PMID- 21025065 TI - The role of personality and environmental factors in obesity. PMID- 21025066 TI - Food intake of college women. PMID- 21025067 TI - Ascorbic acid content of lunches served at school. PMID- 21025068 TI - Study of food selection at the Western Union Cafeteria, New York. PMID- 21025069 TI - Sources of principal nutrients in the diet of a North Carolina village population. PMID- 21025070 TI - Effect of maturity on nutrients of snap beans. PMID- 21025071 TI - The nutrition clinic at Medical College of Virginia. PMID- 21025072 TI - A dietitian serves the community through its social agencies. PMID- 21025073 TI - Organization of an institutional food service for young children. PMID- 21025074 TI - Failure of feather pigmentation in bronze poults due to lysine deficiency. PMID- 21025075 TI - Self selection of diet; selection of purified components. PMID- 21025076 TI - Variability in the calcium metabolism and calcium requirements of adult human subjects. PMID- 21025077 TI - The effect of the citrate ion on the calcium metabolism of adult human subjects. PMID- 21025078 TI - Dental caries in the cotton rat; the effect of the amount of protein, fat and carbohydrate in the diet on the incidence and extent of carious lesions. PMID- 21025079 TI - The influence of autoclaving soybean oil meal on the availability of cystine and methionine for the chick. PMID- 21025080 TI - The carotene content of Cuban foods. PMID- 21025081 TI - The effects of added vitamin A on the conjunctiva and the level of vitamin A in the blood. PMID- 21025082 TI - The nutritional significance of animal protein supplements in the diet of the chick. PMID- 21025083 TI - Pantothenic acid deficiency and reproduction in the rat. PMID- 21025084 TI - The isolation and testing of fecal streptococci. PMID- 21025085 TI - A method for bio-assay for extracts which inhibit gastric secretion. PMID- 21025086 TI - The role of the coenzymes of the B complex vitamins and amino acids in muscle metabolism and balanced nutrition. PMID- 21025087 TI - Intravenous typhoid vaccine therapy in the management of ulcerative colitis. PMID- 21025088 TI - Recurrence rate of symptoms in peptic ulcer patients on conservative medical treatment. PMID- 21025089 TI - Do resin cathartics cause gallbladder contraction? PMID- 21025090 TI - Observations of small and large bowel motility in man. PMID- 21025091 TI - Review of recent literature on amebiasis (1944-1945). PMID- 21025092 TI - Penicillin locally in Vincent's disease. PMID- 21025093 TI - The effect of thiamin deprivation upon gastric secretion in rats. PMID- 21025094 TI - On the tissue aldehyde shift in the rat kidney. PMID- 21025095 TI - Some effects of sex steroids on the gonads of the starling. PMID- 21025096 TI - The distribution of cell types in the anterior hypophysis during late pregnancy and lactation. PMID- 21025097 TI - Prostate and seminal vesicle response to testosterone propionate in intact and castrate rats. PMID- 21025098 TI - The cholesterol and ascorbic acid content of the adrenal, liver, brain, and plasma following hemorrhage. PMID- 21025099 TI - Studies on the role of the liver in the metabolism of progesterone. PMID- 21025100 TI - Vicarious metabolic response; the influence of blood from thyroxinized animals on the oxygen consumption of surviving tissue. PMID- 21025101 TI - Mitosis stimulation in the thyroid gland induced by thiouracil. PMID- 21025102 TI - Adrenal medulla in water diuresis and water intoxication. PMID- 21025103 TI - Studies on water intoxication in adrenalectomized rats and the influence of desoxycorticosterone acetate (DCA) and epinephrine in water diuresis. PMID- 21025104 TI - Peroxidase activity of the thyroid gland under normal and experimental conditions. PMID- 21025105 TI - Effect of thiourea on body fat and liver glycogen of rats. PMID- 21025106 TI - Effect of thiouracil and other compounds on the succinoxidase system of rat thyroid tissue. PMID- 21025107 TI - The effect of adrenalectomy on the accesory reproductive glands of mice castrated for short periods. PMID- 21025108 TI - Studies on the cold test as a method for the assay of adrenal cortical steroids. PMID- 21025109 TI - The assay of adrenal cortical material by means of a glycogen test in the adrenalectomized mouse. PMID- 21025110 TI - The relative potencies of adrenal cortical steroids as determined by a cold protection test and by a glycogen deposition test. PMID- 21025111 TI - Quantitative methods for the bio-assay of the glycogenic activity of steroids and urinary extracts. PMID- 21025112 TI - The effect of partial hepatectomy on the inactivation of alpha-estradiol. PMID- 21025113 TI - Administration of progesterone in the form of microcrystals. PMID- 21025114 TI - A study of progesterone inactivation by the liver after intraportal administration. PMID- 21025115 TI - The general adaptation syndrome and the diseases of adaptation. PMID- 21025116 TI - The proteolytic activity of normal and pathological human thyroid tissue. PMID- 21025117 TI - Adenocarcinoma of the thyroid with hyperthyroidism and functional metastases; studies with thiouracil and radioiodine. PMID- 21025118 TI - Mikulicz's syndrome with fever as an unusual complication of thiouracil therapy. PMID- 21025119 TI - Idiopathic hypoparathyroidism with mental deterioration; effect of treatment on intellectual function. PMID- 21025120 TI - The excretion of neutral 17-ketosteroids in two cases of male pseudohermaphroditism. PMID- 21025121 TI - A study of the diurnal variations in circulating lymphocytes in normal and psychotic subjects. PMID- 21025122 TI - The lymphocyte response to heat stress in normal and psychotic subjects. PMID- 21025123 TI - Stressful psychomotor performance and adrenal cortical function as indicated by the lymphocyte response. PMID- 21025124 TI - Differential blood counts in certain adrenal cortical disorders (Cushing's syndrome, Addison's disease and panhypopituitarism). PMID- 21025125 TI - Antidiuretic activity in the blood of non-pregnant women and women during normal and toxemic pregnancy. PMID- 21025127 TI - [Not Available]. PMID- 21025126 TI - [Not Available]. PMID- 21025128 TI - [Not Available]. PMID- 21025129 TI - [Not Available]. PMID- 21025130 TI - Disability benefits for discharged soldiers; law, regulations and procedure. PMID- 21025132 TI - The social and legal aspects of sexual abnormality. PMID- 21025131 TI - Forensic science laboratories. PMID- 21025133 TI - The relation of hyaluronidase in the seminal fluid to fertility. PMID- 21025134 TI - What is a normal semen; preliminary report. PMID- 21025135 TI - Cell behavior and psychology. PMID- 21025137 TI - MARRIAGE laws in Russia. PMID- 21025136 TI - The legitimacy of artificial insemination. PMID- 21025138 TI - Genetics of the Palomino horse; confirmation of the Salisbury-Britton hypothesis. PMID- 21025139 TI - Natural selection and chromosomal variability in populations of Drosophila funebris. PMID- 21025140 TI - Artificial insemination comes of age. PMID- 21025141 TI - The formation of polynucleated pollen mother-cells in Trillium erectum. PMID- 21025142 TI - Inheritance of indeterminate growth in maize. PMID- 21025143 TI - An inquiry into the causes of breech presentation. PMID- 21025144 TI - An evaluation of the treatment of the persistently unengaged vertex in the multipara. PMID- 21025145 TI - Delivery after cesarean section. PMID- 21025146 TI - A comparative analysis of the diagnosis and treatment of endometriosis, including a report of fifty-three cases of intestinal endometroisis. PMID- 21025147 TI - Asphyxia of the newborn infant. PMID- 21025148 TI - Preconceptional progestin therapy in habitual abortion. PMID- 21025149 TI - The oral use of hexestrol for estrogen deficiency. PMID- 21025150 TI - Intestinal obstruction in gynecology. PMID- 21025151 TI - An evaluation of the Hogben pregnancy test. PMID- 21025152 TI - A possible hepatic (hepatorenal) factor in gynecologic mortality. PMID- 21025153 TI - An evaluation of the Guterman pregnancy test. PMID- 21025154 TI - Uterus didelphys and its clinical significance in pregnancy. PMID- 21025155 TI - Uterus didelphys. PMID- 21025156 TI - Evaluation of a new contrast medium for hysterosalpingography. PMID- 21025157 TI - The combined Manchester-Watkins interposition operation in the treatment of prolapse of the uterus. PMID- 21025158 TI - Neonatal thrombocytopenic purpura. PMID- 21025159 TI - Acute lympathic leucemia occurring during pregnancy. PMID- 21025160 TI - Tuberculous ulcer of the vulva. PMID- 21025161 TI - A comparison of the color chemical test with the Friedman modification of the Aschheim-Zondek test. PMID- 21025162 TI - A congenital anomaly of the vagina with pyocolpos. PMID- 21025163 TI - A simple, inexpensive resuscitation apparatus for the newborn infant. PMID- 21025165 TI - [Not Available]. PMID- 21025164 TI - Excretion of penicillin in human milk following parturition. PMID- 21025166 TI - [Not Available]. PMID- 21025167 TI - [Not Available]. PMID- 21025168 TI - [Not Available]. PMID- 21025169 TI - [Not Available]. PMID- 21025170 TI - TRANSACTIONS of IV All India Obstetric and Gynaecological Congress. PMID- 21025171 TI - The social role of the mother. PMID- 21025173 TI - STANDARDS for obstetrical departments in hospitals. PMID- 21025172 TI - Midwifery delivery services in New Mexico. PMID- 21025174 TI - The Chicago Lying-in Hospital and Dispensary looks ahead. PMID- 21025175 TI - The handicapped child. PMID- 21025176 TI - Vital statistics. PMID- 21025177 TI - The use of maternity services in Middlesbrough. PMID- 21025179 TI - Medicine in the dugout. PMID- 21025178 TI - Medicine: its nature and definition. PMID- 21025180 TI - A list of surgeons in practice in London and its suburbs in 1641. PMID- 21025181 TI - An outline of the achievements of American dermatology arranged in chronological order. PMID- 21025182 TI - The Miller collection of the Library of the Richmond Academy of Medicine. PMID- 21025183 TI - STANDARDS for medical librarianship. PMID- 21025184 TI - The war and the medical library. PMID- 21025185 TI - Yellow fever in New York City. PMID- 21025186 TI - A short classification of medical literature. PMID- 21025187 TI - Tanned human skin. PMID- 21025188 TI - The medical library of St. Luke's Hospital, Chicago. PMID- 21025189 TI - Further comments on the mathematical analysis of evaluating scientific journals. PMID- 21025190 TI - Industrial medicine and homeopathy. PMID- 21025191 TI - Observations on the end results of major surgery. PMID- 21025192 TI - Physical medicine as practiced in a rural hospital. PMID- 21025193 TI - The story of penicillin. PMID- 21025194 TI - Osteopathic management of rheumatoid arthritis; a preliminary report. PMID- 21025195 TI - Planned painless parturition; a future possibility. PMID- 21025197 TI - Virus pneumonitis with complications. PMID- 21025196 TI - Practical aspects of the treatment of chronic systemic infections. PMID- 21025198 TI - Osteopathic lesions and abortions. PMID- 21025199 TI - Early ambulation. PMID- 21025200 TI - A resume of treatment of sinusitis. PMID- 21025201 TI - Management of injuries to the eye and associated structures. PMID- 21025203 TI - Multum in parvo. PMID- 21025202 TI - Care in diagnosis rewarded. PMID- 21025204 TI - The healthy child and how to keep him well. PMID- 21025205 TI - Hospital schools in N.S.W. PMID- 21025206 TI - Tuberculosis, with some references to chest surgery. PMID- 21025207 TI - Thiouracil in the treatment of hyperthyroidism. PMID- 21025208 TI - Diet in pregnancy and lactation. PMID- 21025209 TI - Penicillin treatments. PMID- 21025210 TI - Obstetrics. PMID- 21025211 TI - Cisternal encephalography. PMID- 21025212 TI - Medical illustration. PMID- 21025213 TI - Refresher courses for medical record librarians. PMID- 21025214 TI - OSTEOPATHS score, while physicians squabble. PMID- 21025215 TI - ANAESTHETIC explosion hazards. PMID- 21025216 TI - Practicality of ultraviolet air disinfection determined by hospital survey. PMID- 21025217 TI - When a nun becomes a patient; the hospital Sister as a patient. PMID- 21025219 TI - Organizing the personnel service. PMID- 21025218 TI - When a nun becomes a patient; the teaching Sister as a patient. PMID- 21025220 TI - The danger of exploiting student nurses. PMID- 21025221 TI - Who will pay hospital bills for postwar patients? PMID- 21025222 TI - Three guides to finding a good architect. PMID- 21025223 TI - If I am ever mentally ill again, perhaps the hospitals will be different. PMID- 21025224 TI - Two beds add up to many problems. PMID- 21025225 TI - Planning committee advances the cause of rural health. PMID- 21025227 TI - Economic and psychological historiography. PMID- 21025228 TI - Sociological analysis of Horney and Fromm. PMID- 21025226 TI - Max Weber's interpretation of conduct and history. PMID- 21025229 TI - [Not Available]. PMID- 21025231 TI - [Not Available]. PMID- 21025230 TI - [Not Available]. PMID- 21025232 TI - [Not Available]. PMID- 21025234 TI - Placing the handicapped in jobs. PMID- 21025233 TI - Occupational information in counseling; present practices and historical development. PMID- 21025235 TI - An opportunity to do a professional job. PMID- 21025236 TI - Opportunities in the Veterans Administration for professional counselors. PMID- 21025237 TI - The role of a psychologist in a vocational counseling service. PMID- 21025238 TI - Emotional factors in safety. PMID- 21025239 TI - Job analysis, description and classification. PMID- 21025240 TI - Latin American culture. PMID- 21025242 TI - [Not Available]. PMID- 21025241 TI - The one hundred most eminent Americans. PMID- 21025243 TI - [Not Available]. PMID- 21025244 TI - [Not Available]. PMID- 21025245 TI - [Not Available]. PMID- 21025246 TI - [Not Available]. PMID- 21025247 TI - [Not Available]. PMID- 21025249 TI - [Not Available]. PMID- 21025248 TI - [Not Available]. PMID- 21025250 TI - [Not Available]. PMID- 21025251 TI - [Not Available]. PMID- 21025252 TI - Constitution of liver and spleen as a physical basis for genetic resistance to mouse typhoid. PMID- 21025253 TI - The relation of natural and acquired immunity of various avian hosts to the cryptozoites and metacryptozoites of Plasmodium gallinaceum and Plasmodium relictum. PMID- 21025254 TI - Preliminary report of an outbreak of streptococcal disease caused by a sulfadiazine resistant group A, type 17 hemolytic streptococcus. PMID- 21025255 TI - The interpost dissemination of epidemic strains of hemolytic streptococci by troop movements. PMID- 21025256 TI - An epidemic caused by a sulfadiazine resistant strain of the streptococcus hemolyticus (group A, type 17). PMID- 21025257 TI - An outbreak of sulfadiazine resistant streptococcus infection at Lowry Field, Colorado. PMID- 21025258 TI - Changes in the infectiousness of gametocytes during the course of Plasmodium gallinaceum infections. PMID- 21025259 TI - Effect of quinine on saurian malarial parasites. PMID- 21025260 TI - Endemic typhus in Manila, Philippine Islands; report of cases and identification of the murine rickettsial agent in domestic rats by complement fixation. PMID- 21025262 TI - [Not Available]. PMID- 21025261 TI - [Not Available]. PMID- 21025263 TI - Esophagogastrostomy for cardiospasm. PMID- 21025264 TI - Use of amphetamine in mental diseases. PMID- 21025265 TI - Sodium amytal; its therapeutic and diagnostic uses. PMID- 21025266 TI - Etiology of the jaundice epidemic of 1942-1943. PMID- 21025267 TI - Hemostasis of wounds of the liver. PMID- 21025268 TI - Medical progress in the USSR. PMID- 21025269 TI - [Not Available]. PMID- 21025270 TI - [Not Available]. PMID- 21025271 TI - Penicillin for isolation of bacteria-free culture of Leishmania parasites. PMID- 21025272 TI - Quantitative colorimetric determination of salicylates in blood. PMID- 21025273 TI - Investigations on the new antidiabetic principle (amellin); its role in the reduction of acetone bodies and the increase of alkali reserve of the blood of diabetics. PMID- 21025274 TI - On the mode of action of dicoumarin. PMID- 21025275 TI - Influence of different fats and oils on the composition of body fat and the lipoid content of the liver of rats. PMID- 21025276 TI - Post-mortem studies of starvation cases. PMID- 21025277 TI - Meningococcic infections in an Army staging area; analysis of 63 cases without fatality from the standpoint of early diagnosis and treatment. PMID- 21025278 TI - Meningococcemia; a description of the clinical picture and a comparison of the efficacy of sulfadiazine and penicillin in the treatment of 30 cases. PMID- 21025279 TI - Post-diphtheritic polyneuritis: a report of five cases with albuminocytologic dissociation simulating Guillain-Barre's syndrome. PMID- 21025280 TI - Toxic reactions accompanying second courses of sulfonamides in patients developing toxic reactions during a previous course. PMID- 21025281 TI - Apathetical response to hyperthyroidism; report of two cases. PMID- 21025282 TI - Salicylate toxicity; the probable mechanism of its action. PMID- 21025283 TI - The plasma volume in Laennec's cirrhosis of the liver. PMID- 21025284 TI - Serial prothrombin estimations in cardiac patients; diagnostic and therapeutic implications; use of dicumarol. PMID- 21025285 TI - The postmortem examination in cases of suspected homicide. PMID- 21025286 TI - Excessive self-administered dosages of thyroid extract. PMID- 21025287 TI - Pneumococcic meningitis sucessfully treated with penicillin and sulfadiazine. PMID- 21025288 TI - Spontaneous rupture of the spleen during malaria therapy; report of a case. PMID- 21025289 TI - Idiopathic dilatation of the common bile duct with coexistent primary hepatic carcinoma; report of a case. PMID- 21025290 TI - PRIMARY atypical pneumonia. PMID- 21025291 TI - PHILADELPHIA and American medicine. PMID- 21025292 TI - Treatment of retention of urine in the male. PMID- 21025293 TI - Undulant fever in Kathiawar (Malta fever). PMID- 21025294 TI - A plea for preferential thoracoplasty in early apical cavitation in pulmonary tuberculosis. PMID- 21025295 TI - Retinitis pigmentosa. PMID- 21025296 TI - Diarrhoeas in children. PMID- 21025297 TI - Diagnosis of fever in the tropics; treatment of typhoid fever in childhood. PMID- 21025298 TI - Infantile convulsions. PMID- 21025299 TI - Arsenical dermatitis. PMID- 21025300 TI - Peeps into the past; sketches of the Madras General Hospital in the XIX century. PMID- 21025301 TI - A case of chronic constipation. PMID- 21025302 TI - Allergy due to malaria. PMID- 21025303 TI - Hysterical vomiting. PMID- 21025304 TI - A case of malaria resembling acute nephritis. PMID- 21025305 TI - A case of hysteria, attended with pregnancy. PMID- 21025306 TI - Cases of cancrum oris. PMID- 21025307 TI - Clinical aspects of cardiac murmurs. PMID- 21025308 TI - Prevention of child-birth maternal injuries. PMID- 21025309 TI - Acute ulcer caused by gram-negative fusi-form bacilli. PMID- 21025310 TI - Pneumonic complications in enteric. PMID- 21025311 TI - Bacillary dysentery. PMID- 21025312 TI - Burns and treatment of third degree. PMID- 21025313 TI - Some problems in diagnosis of pulmonary tuberculosis in the tropics. PMID- 21025315 TI - An unusual case of fatal coma. PMID- 21025314 TI - Protein shock therapy; theory and application. PMID- 21025316 TI - A case of abnormal permeability of retinal vessels. PMID- 21025317 TI - A bad case of status epilepticus. PMID- 21025318 TI - Importance of primary disinfection in wounds caused by dog-bite. PMID- 21025319 TI - An unusual case of diabetes mellitus. PMID- 21025320 TI - Nonsuppurative poststreptococcic (rheumatic) pneumonitis; pathologic anatomy and clinical differentiation from primary atypical pneumonia. PMID- 21025321 TI - Danger of intravenous injection of protein solutions after sudden loss of renal tissue. PMID- 21025323 TI - Reiter's disease; review of the literature, with presentation of a case. PMID- 21025322 TI - Sulfadiazine and penicillin for hemolytic streptococcus infections of the upper respiratory tract; an evaluation in tonsillitis, nasopharyngitis and scarlet fever. PMID- 21025324 TI - Cardiac enlargement in fever therapy induced by intravenous injection of typhoid vaccine. PMID- 21025325 TI - Rheumatic fever in naval enlisted personnel; an analysis of the major manifestations observed, the factors involved in its occurrence and the cardiac residua. PMID- 21025326 TI - Cataract extraction. PMID- 21025327 TI - Conjugation of sulfonamides in the intestinal tract of man. PMID- 21025328 TI - Factors determining the hydrolysis of sulfasuxidine and sulfathalidine. PMID- 21025329 TI - Estimation of sulfasuxidine and sulfathalidine. PMID- 21025330 TI - Subacute bacterial endocarditis with case report. PMID- 21025331 TI - [Not Available]. PMID- 21025332 TI - [Not Available]. PMID- 21025333 TI - [Not Available]. PMID- 21025334 TI - [Not Available]. PMID- 21025335 TI - [Not Available]. PMID- 21025336 TI - Surgical aspects of congenital heart disease. PMID- 21025338 TI - Splenic cysts: with a report of a case. PMID- 21025337 TI - Resistant anaemia; a note on the differential diagnosis of pernicious anaemia and familial acholuric jaundice. PMID- 21025339 TI - Significance of the premenstrual fever in pulmonary tuberculosis. PMID- 21025340 TI - Blindness in an urban centre in Nigeria. PMID- 21025342 TI - Facial splint for treatment of Bell's palsy. PMID- 21025343 TI - INDUCTION of ovulation in women. PMID- 21025341 TI - Severe and long-standing headache due to dental and antral infection. PMID- 21025344 TI - Rehabilitation of forces neurosis patients to civilian life. PMID- 21025345 TI - The Health Service Bill. PMID- 21025346 TI - Physical therapy in mental disorder. PMID- 21025347 TI - Homosexuality and the law. PMID- 21025348 TI - Iritis in the rheumatic affections. PMID- 21025349 TI - Prevention of transfusion reactions due to Rh factors. PMID- 21025350 TI - Spontaneous hypoglycaemia associated with epilepsy; subtotal pancreatectomy. PMID- 21025351 TI - Occurrence of ovulation and causes of sterility in metropathia haemorrhagica. PMID- 21025352 TI - Treatment of sulphonamide-resistant gonorrhoea by penicillin. PMID- 21025353 TI - Treatment of lewisite shock with sodium salt solutions. PMID- 21025354 TI - Congenital polycystic disease of the liver and kidneys. PMID- 21025355 TI - A gag for use during electric convulsion therapy. PMID- 21025356 TI - A visit to an Indian leper colony. PMID- 21025357 TI - Care of the chronic sick and of the aged. PMID- 21025358 TI - The Health Service Bill. PMID- 21025359 TI - Ocular signs in the prisoner of war from the Far East. PMID- 21025360 TI - Recent advances in the physicology of vision. PMID- 21025361 TI - The pathogenicity of penicillin-insensitive infection. PMID- 21025363 TI - An impression. PMID- 21025362 TI - Malnutrition in recovered prisoners of war and internees; report of 10 cases evacuated from Thailand. PMID- 21025364 TI - Treatment of acute otitis media by decongestion. PMID- 21025365 TI - A case of indigenous malaria in Northern Ireland. PMID- 21025366 TI - Coma as onset in a case of malaria in England. PMID- 21025367 TI - Finger traps for banjo splint. PMID- 21025368 TI - Apparatus and routine for diabetic ward-tests. PMID- 21025369 TI - Conjunctivitis. PMID- 21025370 TI - [Not Available]. PMID- 21025371 TI - [Not Available]. PMID- 21025372 TI - [Not Available]. PMID- 21025373 TI - [Not Available]. PMID- 21025374 TI - [Not Available]. PMID- 21025375 TI - [Not Available]. PMID- 21025376 TI - [Not Available]. PMID- 21025377 TI - [Not Available]. PMID- 21025378 TI - [Not Available]. PMID- 21025379 TI - [Not Available]. PMID- 21025380 TI - [Not Available]. PMID- 21025381 TI - [Not Available]. PMID- 21025382 TI - [Not Available]. PMID- 21025383 TI - [Not Available]. PMID- 21025384 TI - [Not Available]. PMID- 21025385 TI - [Not Available]. PMID- 21025386 TI - [Not Available]. PMID- 21025387 TI - [Not Available]. PMID- 21025388 TI - [Not Available]. PMID- 21025389 TI - [Not Available]. PMID- 21025390 TI - [Not Available]. PMID- 21025391 TI - [Not Available]. PMID- 21025392 TI - [Not Available]. PMID- 21025393 TI - [Not Available]. PMID- 21025394 TI - [Not Available]. PMID- 21025395 TI - [Not Available]. PMID- 21025396 TI - [Not Available]. PMID- 21025397 TI - [Not Available]. PMID- 21025398 TI - [Not Available]. PMID- 21025399 TI - [Not Available]. PMID- 21025400 TI - [Not Available]. PMID- 21025401 TI - [Not Available]. PMID- 21025402 TI - [Not Available]. PMID- 21025403 TI - [Not Available]. PMID- 21025404 TI - [Not Available]. PMID- 21025405 TI - [Not Available]. PMID- 21025406 TI - [Not Available]. PMID- 21025408 TI - [Not Available]. PMID- 21025407 TI - [Not Available]. PMID- 21025409 TI - [Not Available]. PMID- 21025410 TI - [Not Available]. PMID- 21025411 TI - [Not Available]. PMID- 21025412 TI - [Not Available]. PMID- 21025413 TI - [Not Available]. PMID- 21025414 TI - [Not Available]. PMID- 21025415 TI - [Not Available]. PMID- 21025416 TI - [Not Available]. PMID- 21025418 TI - Disseminated lupus erythematosus. PMID- 21025417 TI - [Not Available]. PMID- 21025419 TI - Modern trends in nursing service demands. PMID- 21025420 TI - Haemoglobin levels of children in British Columbia. PMID- 21025421 TI - The vibration syndrome. PMID- 21025422 TI - Incidence of syphilis in Calcutta before and during the war. PMID- 21025423 TI - Studies in malaria transmission. PMID- 21025424 TI - Paludrine (the new drug) triumphs over malaria. PMID- 21025425 TI - Management of occipito-posterior position. PMID- 21025426 TI - Studies in malaria transmission. PMID- 21025427 TI - Auto-cardiotoxins in acute rheumatic fever. PMID- 21025428 TI - California's State medical schools and public health problems. PMID- 21025429 TI - The relationship between anxiety neurosis and duodenal ulcer with special reference to the x-ray findings and treatment. PMID- 21025430 TI - Pollinosis in Imperial County, California, and Yuma, Arizona. PMID- 21025431 TI - Subdural hydroma; a cause of morbidity after head injury. PMID- 21025432 TI - Chronic leg ulcers of sickle cell anemia; report of case; with reference to recognition. PMID- 21025433 TI - Survey of blood grouping and Rh factor in the Eskimos of the Eastern Arctic, 1945. PMID- 21025434 TI - Calcified gall bladder. PMID- 21025435 TI - Fibrocystic disease of the pancreas in infants. PMID- 21025436 TI - Picrotoxin for barbiturate poisoning. PMID- 21025437 TI - Some aspects of penicillin therapy in early syphilis. PMID- 21025438 TI - The role of penicillin in the treatment of chronic osteomyelitis. PMID- 21025439 TI - Penicillin spray by bulb atomizer. PMID- 21025440 TI - Contusion of the heart. PMID- 21025441 TI - Toxaemia of pregnancy. PMID- 21025443 TI - Chorionepithelioma. PMID- 21025442 TI - Sinusitis. PMID- 21025444 TI - Vibration syndrome. PMID- 21025445 TI - Resuscitation of the severely wounded. PMID- 21025446 TI - Advanced abdominal pregnancy. PMID- 21025447 TI - Acute volvulus of the gallbladder. PMID- 21025448 TI - Partial transposition of the upper abdominal viscera. PMID- 21025449 TI - A malformation of the symmelia type. PMID- 21025450 TI - Cervical cytology tests in cancer diagnosis; glycerine technique for mailing. PMID- 21025451 TI - An improved method of arthrography. PMID- 21025452 TI - Government dominated medicine. PMID- 21025453 TI - HOW the socialist looks at national health service in England. PMID- 21025454 TI - Some things I remember. PMID- 21025455 TI - ATOM bombs and medical schools. PMID- 21025456 TI - What are we willing to pay for health? PMID- 21025457 TI - The history of the 4th General Hospital. PMID- 21025458 TI - [Not Available]. PMID- 21025459 TI - [Not Available]. PMID- 21025460 TI - [Not Available]. PMID- 21025461 TI - [Not Available]. PMID- 21025462 TI - [Not Available]. PMID- 21025463 TI - [Not Available]. PMID- 21025464 TI - [Not Available]. PMID- 21025465 TI - The prevention of blindness. PMID- 21025466 TI - Program and responsibilities of the Veterans Administration for physical and mental health resources for veterans. PMID- 21025467 TI - Medical work at the Newington Veterans Hospital. PMID- 21025468 TI - Lesions of the female external genital tract susceptible to office treatment. PMID- 21025469 TI - Paroxysmal cold hemoglobinuria. PMID- 21025470 TI - Prefrontal lobotomy; a review of recent literature. PMID- 21025471 TI - A private agency serves veterans. PMID- 21025472 TI - A treatment program for the pre-school cerebral palsied child. PMID- 21025474 TI - Industrial injuries to minors. PMID- 21025473 TI - Difficulties in group adjustment encountered by the physically handicapped. PMID- 21025475 TI - Hygenic care of children. PMID- 21025476 TI - Employment for the severely handicapped. PMID- 21025477 TI - A survey among adult cerebral palsied. PMID- 21025478 TI - Physical therapy in a camp for crippled children. PMID- 21025479 TI - [Not Available]. PMID- 21025480 TI - [Not Available]. PMID- 21025481 TI - Newer concepts of peptic ulcer pathogenesis, diagnosis and treatment. PMID- 21025482 TI - Prevalence of brucellosis. PMID- 21025483 TI - Analysis of one hundred cases of minimal pulmonary tuberculosis. PMID- 21025484 TI - Loeffler's syndrome (transient pulmonary infiltrations with eosinophilia); report of a case and a review of the available literature. PMID- 21025485 TI - Bronchoscopy in pulmonary tuberculosis. PMID- 21025487 TI - Management of minimal tuberculosis. PMID- 21025486 TI - The present status of tuberculosis in children. PMID- 21025488 TI - Pregnancy in tuberculosis. PMID- 21025489 TI - Chemotherapy of tuberculosis. PMID- 21025490 TI - Indications for collapse therapy. PMID- 21025491 TI - Recent advances in bronchoscopic technic. PMID- 21025492 TI - The treatment of bronchiectasis. PMID- 21025493 TI - Surgical procedures in nontuberculous diseases. PMID- 21025494 TI - Acute primary diaphragmitis (Hedblom's syndrome). PMID- 21025495 TI - The unexpandable lung. PMID- 21025496 TI - Artificial pneumothorax and its effect upon the pulmonary tissues of normal rabbits. PMID- 21025497 TI - Induced pneumoperitoneum in the treatment of advanced pulmonary tuberculosis in children. PMID- 21025498 TI - Laryngeal tuberculosis. PMID- 21025499 TI - Separation center chest survey. PMID- 21025500 TI - The chest specialist; his training and services. PMID- 21025501 TI - Diasone in the treatment of pulmonary tuberculosis. PMID- 21025502 TI - Dyspnoea and diminished vital capacity as a symptom and a sign in hay fever. PMID- 21025503 TI - Roentgenographic scanning of the chest. PMID- 21025504 TI - Iodized oil in the treatment of chronic bronchitis. PMID- 21025505 TI - Pulmonary disease secondary to cardiospasm, with acid fast bacilli in the sputum; case report. PMID- 21025506 TI - Bulla of the lung. PMID- 21025507 TI - Nebulized penicillin in the treatment of respiratory infection. PMID- 21025508 TI - A tuberculosis survey of a rural mountain county. PMID- 21025509 TI - Bronchial asthma (a case report). PMID- 21025510 TI - The tuberculosis problem of the Union of South Africa. PMID- 21025511 TI - [Not Available]. PMID- 21025512 TI - [Not Available]. PMID- 21025513 TI - [Not Available]. PMID- 21025514 TI - [Not Available]. PMID- 21025515 TI - [Not Available]. PMID- 21025517 TI - [Not Available]. PMID- 21025516 TI - [Not Available]. PMID- 21025518 TI - [Not Available]. PMID- 21025519 TI - [Not Available]. PMID- 21025520 TI - [Not Available]. PMID- 21025521 TI - [Not Available]. PMID- 21025522 TI - Management in prostatic surgery with special reference to operative risk. PMID- 21025523 TI - The assessment of sensory denervation after injuries of peripheral nerves. PMID- 21025524 TI - Post-prandial variation in haemoglobin. PMID- 21025525 TI - Haemolytic streptococci in puerperal sepsis. PMID- 21025526 TI - [Not Available]. PMID- 21025527 TI - [Not Available]. PMID- 21025528 TI - [Not Available]. PMID- 21025529 TI - [Not Available]. PMID- 21025530 TI - [Not Available]. PMID- 21025531 TI - [Not Available]. PMID- 21025532 TI - [Not Available]. PMID- 21025533 TI - [Not Available]. PMID- 21025534 TI - [Not Available]. PMID- 21025535 TI - [Not Available]. PMID- 21025536 TI - [Not Available]. PMID- 21025537 TI - [Not Available]. PMID- 21025538 TI - [Not Available]. PMID- 21025539 TI - [Not Available]. PMID- 21025540 TI - [Not Available]. PMID- 21025541 TI - The influence of the endocrines on the skeleton. PMID- 21025542 TI - The Sturge-Weber syndrome; report of a case. PMID- 21025543 TI - A case of bronchiectasis simulating empyema. PMID- 21025544 TI - [Not Available]. PMID- 21025545 TI - [Not Available]. PMID- 21025546 TI - Value of the Miller-Abbott tube in surgery; technique of introduction. PMID- 21025548 TI - Ulcerative colitis of unexplained origin. PMID- 21025547 TI - Supernumerary breast; report of a case with fibro-adenoma. PMID- 21025549 TI - Avulsion of the distal tendon of the biceps brachii muscle. PMID- 21025550 TI - Leiomyosarcoma of the bladder; report of a case. PMID- 21025551 TI - Myxoma; report of a case. PMID- 21025552 TI - The status of postpartum hemorrhage. PMID- 21025553 TI - The uneasy child. PMID- 21025554 TI - Lupus vulgaris. PMID- 21025555 TI - Penicillin ointment in the treatment of infective diseases of the skin. PMID- 21025556 TI - Congenital polycystic disease of the liver and kidneys. PMID- 21025558 TI - Otomycosis. PMID- 21025557 TI - Essential hypertension. PMID- 21025559 TI - Large-round-cell sarcoma of the small intestine. PMID- 21025560 TI - [Not Available]. PMID- 21025561 TI - BILLS pertaining to mental hygiene which were introduced in the 1945 legislature. PMID- 21025562 TI - HONOLULU County Medical Library. PMID- 21025563 TI - Herniation of the intervertebral disc; a systematized technique for the investigation and treatment of lumbosacral and low lumbar lesions. PMID- 21025564 TI - Encysted pleural effusions. PMID- 21025565 TI - The pathogenesis of pulmonary atelectasis. PMID- 21025566 TI - Mediastinal emphysema. PMID- 21025567 TI - An unusual developmental abnormality of the arms. PMID- 21025568 TI - Analysis of 242 cases of sprue in Indian troops. PMID- 21025569 TI - On the toxicity of some organic antimonial drugs used for the treatment of kala azar. PMID- 21025570 TI - The cause of hyperglycaemia under general anaesthesia. PMID- 21025571 TI - Novocaine infiltration in acute sprains. PMID- 21025573 TI - The burning-feet syndrome. PMID- 21025572 TI - A note on phlyctenular ophthalmia in adults. PMID- 21025574 TI - A case of lumbo-sacral intervertebral disc herniation causing sciatica. PMID- 21025575 TI - Penicillin in the treatment of agranulocytosis. PMID- 21025576 TI - A case of scleroderma with sclerodactyly. PMID- 21025577 TI - The blood-bank at the Tata Memorial Hospital, Bombay. PMID- 21025578 TI - The bacterial content of the Calcutta milk supply; suggested milk bacteriological standards. PMID- 21025579 TI - Nutritional diseases. PMID- 21025580 TI - Sexual crimes, indecency and ethics. PMID- 21025581 TI - Post-typhoid palatal paralysis. PMID- 21025582 TI - SCRUB typhus. PMID- 21025583 TI - Heart failure. PMID- 21025584 TI - Recent trends in the chemotherapy of burns; with particular reference to second degree areas. PMID- 21025585 TI - Endocrinopathies in young boys. PMID- 21025586 TI - The obstetrical significance of pelvic roentgenometry. PMID- 21025587 TI - Primary mediastinal tuberculosis in children. PMID- 21025588 TI - Some problems of vitamin dosage. PMID- 21025589 TI - Hydrotherapy. PMID- 21025590 TI - The mission of a medical school. PMID- 21025591 TI - Sympathectomy for hypertension. PMID- 21025592 TI - Fractures of the os calcis. PMID- 21025593 TI - Report on a tuberculin survey in an urban area. PMID- 21025594 TI - Tuberculin survey in an industrial school, County Dublin. PMID- 21025595 TI - Mass miniature radiography of children. PMID- 21025596 TI - Acute inversion of uterus. PMID- 21025597 TI - Biological variations. PMID- 21025598 TI - Penicillin alone in neurosyphilis. PMID- 21025599 TI - Folic acid therapy in the anemias of infancy and childhood. PMID- 21025600 TI - Filariasis in the serviceman; retrospect and prospect. PMID- 21025601 TI - Coronary occlusion in Negroes. PMID- 21025602 TI - Atabrine as a cause of fatal exfoliative dermatitis and hepatitis. PMID- 21025603 TI - Treatment of a seriously ill asthmatic patient. PMID- 21025604 TI - Multiple cases of choriomeningitis in an apartment harboring infected mice. PMID- 21025605 TI - Chronic porphyria. PMID- 21025606 TI - Common duct stone relieved by injection of nupercaine solution into T tube. PMID- 21025607 TI - Official statement concerning streptomycin. PMID- 21025608 TI - Some contributions from the sister sciences. PMID- 21025610 TI - The treatment of hyperthyroidism with radioactive iodine. PMID- 21025609 TI - Radioactive iodine in the study of thyroid physiology; the use of radioactive iodine therapy in hyperthyroidism. PMID- 21025611 TI - Surgical aspects of amebic dysentery. PMID- 21025612 TI - Life expectancy in angina pectoris. PMID- 21025613 TI - The syndrome of airblast concussion; cerebral. PMID- 21025614 TI - Treatment of headache with intravenous sodium nicotinate. PMID- 21025615 TI - Frontal osteomyelitis with subdural abscess and hemiplegia after frontal sinusitis. PMID- 21025616 TI - Gastroscopy in acute and chronic hepatitis. PMID- 21025617 TI - MEDICAL licensure statistics for 1945. PMID- 21025618 TI - Therapeutic results in rheumatoid arthritis. PMID- 21025619 TI - Streptomycin therapy in Hemophilus influenzae pulmonary infections. PMID- 21025620 TI - Heparin therapy in acute deep venous thrombosis. PMID- 21025621 TI - Effect of antepartum vitamin K on retinal hemorrhage. PMID- 21025622 TI - Relation of tobacco smoking to arteriosclerosis obliterans in diabetes mellitus. PMID- 21025623 TI - Rheumatic fever in naval enlisted personnel; the physiologic and toxic effects of intensive salicylate therapy in acute cases. PMID- 21025624 TI - Jaundice caused by perforation of a duodenal ulcer. PMID- 21025625 TI - The development of prepayment hospital and medical plan. PMID- 21025626 TI - The Michigan State Medical Society's plan for providing medical care for beneficiaries of the Veterans' Administration. PMID- 21025627 TI - The clinical recognition coronary artery insufficiency. PMID- 21025628 TI - Volvulus of the sigmoid colon; discussion and case report. PMID- 21025629 TI - The graduate record examination as an aid in the selection of medical students. PMID- 21025630 TI - The measurement of medical aptitude. PMID- 21025631 TI - Interest and attitude as factors in achievement in medical school. PMID- 21025632 TI - Social and environmental factors in medicine. PMID- 21025633 TI - The German university medical schools during the occupation. PMID- 21025634 TI - The future of electronics and electrical instrumentation as related to medicine. PMID- 21025635 TI - Some reflections on medical progress. PMID- 21025636 TI - Some recent advances in tropical medicine. PMID- 21025637 TI - Therapeutics of the vitamin B complex. PMID- 21025639 TI - Blood transfusions in a small hospital. PMID- 21025638 TI - Antagonism in drug action. PMID- 21025640 TI - Failure of local fluid loss to account for death in experimental shock. PMID- 21025641 TI - Blood volume in clinical shock; mixing time and disappearance rate of T-1824 in normal subjects and in patients in shock; determination of plasma volume in man from 10-minute sample. PMID- 21025642 TI - Blood volume in clinical shock; the extent and cause of blood volume reduction in traumatic, hemorrhagic, and burn shock. PMID- 21025643 TI - Effect of administration of essential amino acids on utilization of dietary protein in malnutrition among war casualties. PMID- 21025644 TI - The absorption, excretion, and destruction of orally administered penicillin. PMID- 21025645 TI - Treatment of experimental uremia by means of peritoneal irrigation. PMID- 21025646 TI - The role of colloid and of saline in the treatment of shock. PMID- 21025647 TI - A comparison of the effects of high and low viscosity gelatins after their intravenous injection in man. PMID- 21025648 TI - Central venous pressure in relation to cardiac competence, blood volume and exercise. PMID- 21025649 TI - Chloride excretion during glycosuria in patients with diabetes. PMID- 21025650 TI - Estimation of blood volume from change in blood specific gravity following a plasma infusion. PMID- 21025651 TI - The isolation of poliomyelitis virus from human extra-neural sources; comparison of virus content of pharyngeal swabs, oropharyngeal washings, and stools of patients. PMID- 21025652 TI - The isolation of poliomyelitis virus from human extra-neural sources; comparison of virus content of blood, oropharyngeal washings, and stools of contacts. PMID- 21025653 TI - The isolation of poliomyelitis virus from human extra-neural sources; persistence of virus in stools after acute infection. PMID- 21025654 TI - The isolation of poliomyelitis virus from human extra-neural sources; search for virus in the blood of patients. PMID- 21025655 TI - Plasma substitutes; human and animal globin related to the production of hemoglobin and plasma protein; dog hemoglobin utilization improved by methionine but not by isoleucine. PMID- 21025656 TI - The absence of antibody in the macrophages during maximum antibody formation. PMID- 21025657 TI - The activation of skin grafts. PMID- 21025658 TI - The effect of high pressures on hemagglutinating antibodies. PMID- 21025659 TI - Factors affecting the growth of tubercle bacilli in liquid media. PMID- 21025660 TI - The site of angiotonin destruction. PMID- 21025661 TI - Infective hepatitis. PMID- 21025662 TI - Psychosurgery. PMID- 21025663 TI - The Central Drugs Laboratory; a plea for its early establishment. PMID- 21025664 TI - Penicillin therapy in mofussil. PMID- 21025665 TI - Use of penicillin in multiple venereal infections. PMID- 21025666 TI - Pharmacy Bill. PMID- 21025667 TI - Gerontology and the eye, with some remarks on old age. PMID- 21025668 TI - Uveitis in some systemic diseases. PMID- 21025669 TI - Notes on glaucoma for the general practitioner. PMID- 21025670 TI - Penicillin in ophthalmology. PMID- 21025671 TI - Myopia and the school child. PMID- 21025672 TI - Progress in industrial ophthalmology. PMID- 21025673 TI - Concomitant squint. PMID- 21025674 TI - Sore eyes. PMID- 21025675 TI - Some problems of lighting. PMID- 21025676 TI - Education of the visually-handicapped child in Indianapolis public schools. PMID- 21025677 TI - Trachoma and its political complications in Indiana. PMID- 21025678 TI - Rules and regulations regarding osteopaths. PMID- 21025679 TI - Legislation affecting the Indiana State Board of Health. PMID- 21025680 TI - A pollen refuge at home; a case report. PMID- 21025682 TI - Is the incidence of gastric cancer overrated? PMID- 21025681 TI - The use of penicillin in diseases of the eye, ear, nose and throat. PMID- 21025683 TI - [CASE of amebiasis, with primary involvement mainly of the appendix]. PMID- 21025684 TI - The recognition, evaluation and management of heart disease in pregnancy. PMID- 21025685 TI - The treatment of chest injuries. PMID- 21025686 TI - The Still-Chauffard syndrome; rheumatoid arthritis with systemic manifestations. PMID- 21025687 TI - The atomic bomb. PMID- 21025688 TI - Basic principles in the treatment of cancer. PMID- 21025689 TI - How permanent are the results of transurethral prostatic resection? PMID- 21025690 TI - Forty years of medicine. PMID- 21025691 TI - Granuloma inguinale; a study of 200 cases. PMID- 21025692 TI - The recognition of ureteropelvic obstruction. PMID- 21025693 TI - The bone graft in orthopedic surgery. PMID- 21025695 TI - A hodge-podge of past experiences. PMID- 21025694 TI - Sarcoidosis; report of case. PMID- 21025696 TI - Malignant lymphoma. PMID- 21025697 TI - Important infections in children. PMID- 21025698 TI - Limitations of antirabic treatment. PMID- 21025699 TI - Medical Service Administration of New Jersey; Medical Surgical Plan of New Jersey. PMID- 21025700 TI - [Not Available]. PMID- 21025701 TI - [Not Available]. PMID- 21025702 TI - [Not Available]. PMID- 21025703 TI - [Not Available]. PMID- 21025704 TI - [Not Available]. PMID- 21025705 TI - [Not Available]. PMID- 21025706 TI - [Not Available]. PMID- 21025707 TI - [Not Available]. PMID- 21025708 TI - [Not Available]. PMID- 21025709 TI - [Not Available]. PMID- 21025710 TI - [Not Available]. PMID- 21025711 TI - [Not Available]. PMID- 21025712 TI - [Not Available]. PMID- 21025713 TI - [Not Available]. PMID- 21025714 TI - [Not Available]. PMID- 21025715 TI - [Not Available]. PMID- 21025716 TI - MEDICAL care for veterans. PMID- 21025717 TI - Headaches from the otologist's point of view. PMID- 21025718 TI - Ocular causes of headache. PMID- 21025719 TI - Hypertension; remarks concerning its cause and treatment. PMID- 21025720 TI - The prognosis of renal tuberculosis, treated by nephrectomy. PMID- 21025721 TI - Dystrophia myotonica; report of two cases, with associated hyperostosis frontalis interna in one. PMID- 21025722 TI - Some newer uses of roentgen therapy. PMID- 21025723 TI - Symptomatology of acute obstruction of the ileum. PMID- 21025724 TI - Subacute bacterial endocarditis clinically cured with large doses of penicillin by continuous intramuscular drip. PMID- 21025725 TI - Syndrome characteristic for menopause, ovarian hypofunction and castration in the human female. PMID- 21025726 TI - Surgical treatment of bronchiectasis. PMID- 21025727 TI - Psychosomatic problems in an Army general hospital. PMID- 21025728 TI - Medical aspect of peptic ulcer. PMID- 21025729 TI - Improved distribution of medical care. PMID- 21025730 TI - Insufflation of the Fallopian tubes in sterility. PMID- 21025731 TI - Amoebic appendicitis. PMID- 21025732 TI - Can Palestine be freed from leprosy? PMID- 21025733 TI - Intracranial complications of middle ear inflammations, jugular-bulbo-sinus thrombosis (a new treatment). PMID- 21025735 TI - NEW DRUG against malaria. PMID- 21025734 TI - The clinical significance of the Rh. factor. PMID- 21025736 TI - Manetol and larostidine in massive gastric haemorrhage. PMID- 21025737 TI - The prolonged use of mercurial diuretics in congestive heart disease. PMID- 21025738 TI - Diagnosis and treatment of infertility due to anovulation. PMID- 21025739 TI - Exophthalmic goiter; report of interesting cases. PMID- 21025740 TI - Preoperative and postoperative care of laparotomy patients. PMID- 21025741 TI - Air hygiene in dressing-rooms for burns or major wounds. PMID- 21025742 TI - Psychological aspects of psoriasis. PMID- 21025743 TI - Food yeast in tropical malnutrition. PMID- 21025744 TI - Funiculitis in British troops in Ceylon. PMID- 21025745 TI - Paraschmitz dysentery in West Africa. PMID- 21025746 TI - Fat-absorption in tropical sprue. PMID- 21025747 TI - Sternal-puncture needle. PMID- 21025748 TI - United Nations Health Organisation. PMID- 21025749 TI - NUTRITION IN EUROPE. PMID- 21025750 TI - Tottenham. PMID- 21025751 TI - New remedy for lupus. PMID- 21025752 TI - Medico-sociological problems of an ageing population. PMID- 21025753 TI - Air hygiene in dressing-rooms for burns or major wounds. PMID- 21025754 TI - Treatment of open fractures of the femoral diaphysis. PMID- 21025755 TI - Mechanical excitability of regenerating nerve-fibres. PMID- 21025756 TI - Value of Tinel's sign. PMID- 21025757 TI - VENEREAL diseases and compulsion. PMID- 21025758 TI - Disability and disablement; the medical aspect. PMID- 21025759 TI - Research in mental deficiency. PMID- 21025760 TI - [Not Available]. PMID- 21025761 TI - [Not Available]. PMID- 21025762 TI - [Not Available]. PMID- 21025763 TI - [Not Available]. PMID- 21025764 TI - [Not Available]. PMID- 21025765 TI - [Not Available]. PMID- 21025766 TI - [Not Available]. PMID- 21025767 TI - [Not Available]. PMID- 21025768 TI - The Institute of Blood Transfusion of the Polish Red Cross. PMID- 21025769 TI - [Not Available]. PMID- 21025770 TI - [Not Available]. PMID- 21025771 TI - [Not Available]. PMID- 21025772 TI - [Not Available]. PMID- 21025773 TI - [Not Available]. PMID- 21025774 TI - [Not Available]. PMID- 21025775 TI - [Not Available]. PMID- 21025777 TI - The future teaching of obstetrics and gynaecology; postgraduate training. PMID- 21025776 TI - The future teaching of obstetrics and gynaecology; undergraduate training. PMID- 21025779 TI - Clinical photography. PMID- 21025778 TI - Planning obstetrics. PMID- 21025780 TI - Early British medical botanists (1500-1650). PMID- 21025781 TI - The reduction of neonatal mortality. PMID- 21025782 TI - Maternity hospitals of Greater Winnipeg. PMID- 21025783 TI - Dermatomyositis. PMID- 21025784 TI - Urachal dermoid. PMID- 21025785 TI - Ovarian cysts; physiology and pathology. PMID- 21025786 TI - Observations on intussusception. PMID- 21025787 TI - Mothers and children. PMID- 21025788 TI - Brucellosis. PMID- 21025789 TI - Etiology of polyarteritis nodosa. PMID- 21025790 TI - The incidence of primary carcinoma of the lung. PMID- 21025791 TI - Notes on streptomycin. PMID- 21025793 TI - Pellagra. PMID- 21025792 TI - Thrombocytopenic purpura; a report of two cases. PMID- 21025794 TI - Some modern trends of medical education. PMID- 21025795 TI - Advantages of fascial sutures in hernia operations. PMID- 21025796 TI - [Not Available]. PMID- 21025797 TI - [Not Available]. PMID- 21025798 TI - Evolution of cataract operation. PMID- 21025799 TI - HORMONES and cancer. PMID- 21025800 TI - VITAMINS in medical practice. PMID- 21025802 TI - SUMMARY of the report of the Health Survey and Development Committee. PMID- 21025801 TI - Importance of treatment of the nose and throat in cases of asthma. PMID- 21025803 TI - What makes a prepay plan click; how the Massachusetts Medical Service chalked up its remarkable record. PMID- 21025804 TI - Woman doctors. PMID- 21025805 TI - Hookworm disease in Australian soldiers, with reports of cases. PMID- 21025806 TI - Some observations concerning the use of hypnosis as a substitute for anaesthesia. PMID- 21025807 TI - The anti-O agglutinin in human blood, with the report of a case of its occurrence. PMID- 21025808 TI - Chondritis of the patella. PMID- 21025809 TI - Treatment of suppurative tenosynovitis in the fingers. PMID- 21025810 TI - DDT poisoning in man. PMID- 21025811 TI - A short note on the changing outlook in osteomyelitis brought about by the introduction of penicillin. PMID- 21025812 TI - Post-abortional tetanus with recovery. PMID- 21025813 TI - A case of gunshot wound of the large and small intestines. PMID- 21025814 TI - A psychiatric programme for peace. PMID- 21025815 TI - A radiographic analysis of spondylolisthesis. PMID- 21025816 TI - Staphylococcal enteritis in children. PMID- 21025817 TI - The tuberculin patch test; a comparison with the Mantoux test. PMID- 21025818 TI - The empirical use of penicillin for a sulphonamide resistant patient. PMID- 21025819 TI - Columnar-celled carcinoma of the rectum treated by radon; preliminary report, sixteen months after treatment. PMID- 21025820 TI - Sudeck's post-traumatic bone dystrophy. PMID- 21025821 TI - War-time developments of anaesthesia. PMID- 21025822 TI - Penicillin in the treatment of eye infections. PMID- 21025823 TI - A challenge to medical thought. PMID- 21025824 TI - Management of the child with rheumatic carditis. PMID- 21025825 TI - Specialisation in medicine. PMID- 21025826 TI - A case of cysticercosis calcificans. PMID- 21025827 TI - The treatment of hysteria. PMID- 21025828 TI - The reduction of mortality and morbidity by elective alimentary rest, after appendicectomy. PMID- 21025829 TI - Tuberculosis. PMID- 21025830 TI - British conceptions of amebic dysentery. PMID- 21025831 TI - Penicillin a specific in acute infectious epidemic diarrheas of children and the newborn. PMID- 21025832 TI - Newer concepts of medical treatment and aid to the surgery of thyrotoxicosis. PMID- 21025833 TI - Electroencephalographic studies in epilepsy. PMID- 21025834 TI - Progressive idiopathic atrophy of the skin with depigmentation. PMID- 21025835 TI - A day in the office of a psychiatrist. PMID- 21025836 TI - The art of medicine. PMID- 21025837 TI - NUTRITION in Newfoundland. PMID- 21025839 TI - The treatment of chronic otorrhoea by zinc ionisation. PMID- 21025838 TI - The surgical relief of pain. PMID- 21025840 TI - Cancer of the breast. PMID- 21025841 TI - The history of medicine. PMID- 21025842 TI - [Not Available]. PMID- 21025843 TI - [Not Available]. PMID- 21025844 TI - [Not Available]. PMID- 21025845 TI - [Not Available]. PMID- 21025846 TI - [Not Available]. PMID- 21025847 TI - [Not Available]. PMID- 21025848 TI - [Not Available]. PMID- 21025850 TI - Mice, men, malignancy. PMID- 21025849 TI - Neurology in the Middle East and India. PMID- 21025851 TI - The effect of prostigmin in cerebral palsy. PMID- 21025852 TI - Malaria. PMID- 21025853 TI - Malaria in Minnesota. PMID- 21025854 TI - Cystic fibrosis of the pancreas. PMID- 21025855 TI - A new method for cutting full-thickness or split-thickness skin grafts. PMID- 21025856 TI - Diagnostic case presentation. PMID- 21025857 TI - Spontaneous perforation of esophagus. PMID- 21025858 TI - The management and end results in forty-five cases of breech presentation in private practice. PMID- 21025859 TI - Uterine bleeding, organic and functional; diagnosis and treatment. PMID- 21025860 TI - The modern treatment of burns. PMID- 21025861 TI - The general practitioner in the cancer program. PMID- 21025862 TI - Cancer versus physicians and the public. PMID- 21025863 TI - [Not Available]. PMID- 21025864 TI - The problem of nutrition in the postoperative care of abdominal wounds of warfare. PMID- 21025865 TI - Coarctation of the aorta; a report of two cases. PMID- 21025866 TI - Psychogenic factors in the etiology of diabetes. PMID- 21025867 TI - Carcinoma of the prostate. PMID- 21025868 TI - Carcinoma of stomach with metastasis to one lymph node. PMID- 21025869 TI - Cirrhosis of liver, alcoholic type. PMID- 21025870 TI - Cancer of the larynx and of the pharynx. PMID- 21025871 TI - The need for a better appreciation of the value of multiple precordial leads. PMID- 21025873 TI - Complications of obesity. PMID- 21025872 TI - Roentgen pelvimetry. PMID- 21025874 TI - Rupture of the deep epigastric artery. PMID- 21025875 TI - Streptomycin in the treatment of a case of persistent urinary infection. PMID- 21025876 TI - The conservative treatment of pilonidal cyst. PMID- 21025877 TI - Problems of peptic ulcer in the armed forces and in the returned soldiers. PMID- 21025878 TI - The obstetric forceps. PMID- 21025879 TI - Problems in preventing infections in newborn nurseries. PMID- 21025880 TI - Congenital hemolytic disease and erythroblastosis fetalis; two disease syndromes; a preliminary report. PMID- 21025881 TI - Ventricular fibrillation persisting thirty minutes after clinical death. PMID- 21025882 TI - Sequelae following oral and topical use of penicillin. PMID- 21025883 TI - Acute lupus erythematosus disseminata treated with penicillin. PMID- 21025884 TI - INCREASED use of DDT. PMID- 21025885 TI - Tropical lichen planus, New Guinea variety; a clinical report on 24 cases. PMID- 21025886 TI - Bicipital syndromes and their treatment. PMID- 21025887 TI - Inhalation treatment of bronchial asthma. PMID- 21025888 TI - A report on poliomyelitis cases from the Hospital for Special Surgery of New York City. PMID- 21025889 TI - The prognostic value of the sodium amytal test in hypertension managed by thoracolumbar sympathectomy. PMID- 21025890 TI - Proctoscopy and barium colon study in the diagnosis of rectal conditions. PMID- 21025891 TI - Occult maxillary antrum infection. PMID- 21025892 TI - Para-esophageal hiatal hernia; a case manifesting gastrointestinal and cardiac symptoms and presenting itself on x-ray as a mediastinal tumor. PMID- 21025893 TI - Ovarian cyst in the content of inguinal hernial sac. PMID- 21025894 TI - Etiology of thrombo-angiitis obliterans in relation to its therapy. PMID- 21025895 TI - Conquering arthritis and rheumatism. PMID- 21025896 TI - Functional recovery of war wounds of the extremities. PMID- 21025897 TI - The medical history of a Pacific veteran. PMID- 21025898 TI - Tropical disease in discharged military personnel; malaria. PMID- 21025899 TI - Hyperthyroidism; accuracy of diagnosis mandatory in treatment with thiouracil. PMID- 21025900 TI - Atrophic arthritis; ethiology and treatment. PMID- 21025901 TI - Metabolic arthritides. PMID- 21025903 TI - Osteoarthritis. PMID- 21025902 TI - Diseases simulating arthritis. PMID- 21025904 TI - Surgery of the arthritides. PMID- 21025905 TI - The medical approach to massive gastrointestinal hemorrhage. PMID- 21025906 TI - Surgical aspects of massive gastrointestinal hemorrhage. PMID- 21025907 TI - Massive gastrointestinal hemorrhage from primary gallbladder disease. PMID- 21025908 TI - Congenital malrotation of large bowel with obstruction. PMID- 21025909 TI - Cerebellar medulloblastoma, with spontaneous generalized infiltration of piaarachnoid. PMID- 21025910 TI - The Guillain-Barre syndrome; report of a case associated with acute infectious hepatitis. PMID- 21025911 TI - Treatment of acute hematogenous osteomyelitis with penicillin. PMID- 21025912 TI - What lessons have we learned in military neuropsychiatry that have application for civilian life? PMID- 21025913 TI - Infantile paralysis a complication of influenza. PMID- 21025914 TI - An effective drug in the management of cough and hemoptysis in pulmonary tuberculosis. PMID- 21025915 TI - The problem of reconditioning and rehabilitation as related to cardiac diseases. PMID- 21025916 TI - Thoraco-lumbar sympathectomy operation for high blood pressure. PMID- 21025917 TI - Ileus complicating infectious hepatitis; a case report. PMID- 21025918 TI - Brain abscess associated with congenital heart disease. PMID- 21025919 TI - Early occurrence of melanotic sarcoma of the choroid. PMID- 21025920 TI - An evaluation of criteria useful in the differentiation of benign and malignant lesions of the stomach. PMID- 21025921 TI - Shoulder and arm pain of scalenus anticus origin. PMID- 21025922 TI - Occlusive vascular diseases in the lower extremities; diagnosis and differential diagnosis. PMID- 21025923 TI - Tuberculosis control in Philadelphia. PMID- 21025924 TI - Volvulus and gangrene of the sigmoid complicated by Manson's schistosomiasis. PMID- 21025925 TI - Cancer of the rectum. PMID- 21025926 TI - Management of cleft lip and palate. PMID- 21025927 TI - Observations on the pathology of peripheral vascular disease. PMID- 21025928 TI - A new test for pregnancy. PMID- 21025929 TI - An unusual tumour in the umbilical region. PMID- 21025930 TI - Simplified penicillin treatment of lymphogranuloma inguinale and other venereal diseases in West African troops. PMID- 21025931 TI - [Not Available]. PMID- 21025932 TI - [Not Available]. PMID- 21025933 TI - [Not Available]. PMID- 21025934 TI - [Not Available]. PMID- 21025935 TI - [Not Available]. PMID- 21025936 TI - [Not Available]. PMID- 21025937 TI - [Not Available]. PMID- 21025938 TI - [Not Available]. PMID- 21025939 TI - [Not Available]. PMID- 21025940 TI - [Not Available]. PMID- 21025941 TI - [Not Available]. PMID- 21025942 TI - [Not Available]. PMID- 21025943 TI - [Not Available]. PMID- 21025944 TI - [Not Available]. PMID- 21025945 TI - [Not Available]. PMID- 21025946 TI - [Not Available]. PMID- 21025947 TI - [Not Available]. PMID- 21025948 TI - [Not Available]. PMID- 21025949 TI - Vitamin A; deficiency and excess in relation to skeletal growth. PMID- 21025950 TI - Fatigue and weakness of allergic origin; to be differentiated from nervous fatigue or neurasthenia. PMID- 21025951 TI - The quantitative determination of a pepsin-like substance in the urine of normal individuals and of patients with pernicious anemia. PMID- 21025952 TI - The present status of penicillin in the treatment of syphilis. PMID- 21025953 TI - Acute gastric volvulus. PMID- 21025954 TI - Lymphoblastoma of the small intestine; report of case. PMID- 21025955 TI - Treatment of hypersensitiveness to cold with benadryl; report of a case. PMID- 21025956 TI - Infiltrating benign lipomas of the extremities; report of two cases. PMID- 21025958 TI - Primary carcinoma of the fallopian tubes. PMID- 21025957 TI - Cranioplasty with tantalum plate; a new method of forming the plate prior to operation. PMID- 21025959 TI - Cardiac clinics; the historic development of knowledge relating to the coronary circulation and its diseases; twentieth century to 1915. PMID- 21025961 TI - [Not Available]. PMID- 21025960 TI - [Not Available]. PMID- 21025962 TI - [Not Available]. PMID- 21025963 TI - [Not Available]. PMID- 21025964 TI - Infection and war. PMID- 21025965 TI - The elastic element of skeletal muscle. PMID- 21025966 TI - Recent contributions to the extrapyramidal system. PMID- 21025967 TI - Pathology of otosclerosis. PMID- 21025968 TI - Accurate placement of minute lesions in the brain of the albino rat. PMID- 21025969 TI - Spontaneous rupture of the heart; a clinical-pathological correlation with the presentation of twelve cases. PMID- 21025970 TI - Early medical books in the Archibald Church Library; pediatrics. PMID- 21025971 TI - The birth of a society. PMID- 21025972 TI - The doctors look at music. PMID- 21025973 TI - The painful hip of adults; their prevention and treatment. PMID- 21025974 TI - The treatment of traumatic perforations with report of two cases. PMID- 21025975 TI - Differential diagnosis of chest pain. PMID- 21025976 TI - [Not Available]. PMID- 21025977 TI - [Not Available]. PMID- 21025978 TI - [Not Available]. PMID- 21025979 TI - [Not Available]. PMID- 21025980 TI - [Not Available]. PMID- 21025981 TI - [Not Available]. PMID- 21025982 TI - [Not Available]. PMID- 21025983 TI - [Not Available]. PMID- 21025984 TI - [Not Available]. PMID- 21025986 TI - [Not Available]. PMID- 21025985 TI - [Not Available]. PMID- 21025987 TI - [Not Available]. PMID- 21025988 TI - [Not Available]. PMID- 21025989 TI - [Not Available]. PMID- 21025990 TI - [Not Available]. PMID- 21025991 TI - [Not Available]. PMID- 21025992 TI - [Not Available]. PMID- 21025993 TI - [Not Available]. PMID- 21025994 TI - [Not Available]. PMID- 21025995 TI - [Not Available]. PMID- 21025996 TI - [Not Available]. PMID- 21025998 TI - Out-patient electric convulsive therapy. PMID- 21025999 TI - RHODE ISLAND blood-plasma program. PMID- 21025997 TI - [Not Available]. PMID- 21026000 TI - R.I. Hospital refresher courses for veteran-physicians. PMID- 21026001 TI - RINGWORM of the scalp. PMID- 21026002 TI - [Not Available]. PMID- 21026003 TI - [Not Available]. PMID- 21026004 TI - [Not Available]. PMID- 21026006 TI - [Not Available]. PMID- 21026005 TI - [Not Available]. PMID- 21026007 TI - Cardiac problems in a general hospital overseas. PMID- 21026008 TI - A consideration of certain fractures of the ankle. PMID- 21026009 TI - Treatment of creeping eruption (larva migrans). PMID- 21026010 TI - Dermatitis hypostatica; comvined dermatological and surgical treatment. PMID- 21026011 TI - Virus stomatitis and virus diarrhea of infants and young children. PMID- 21026012 TI - What is wrong with the dyspeptic whose findings are all negative? PMID- 21026014 TI - The febrile asthmatic. PMID- 21026013 TI - Recent advances in methods of hastening convalescence through exercise. PMID- 21026015 TI - Treatment of roentgen sickness with oral administration of pyridoxine hydrochloride (vitamin B6). PMID- 21026016 TI - Anorexia nervosa with special regard to insulin therapy. PMID- 21026017 TI - State medicolegal examiners. PMID- 21026018 TI - A proposed program for more adequate medical care and hospitalization in North Carolina. PMID- 21026019 TI - Some observation on the Rh factor. PMID- 21026021 TI - A resume of the management of cancer of the rectum and colon. PMID- 21026020 TI - Role of stellate ganglion block in certain neurologic disorders. PMID- 21026022 TI - Why all States need a basic science law. PMID- 21026024 TI - Urological problems in transverse myelitis. PMID- 21026023 TI - Synthetic vitamin-K in the treatment of urticaria. PMID- 21026025 TI - The actions of digitalis. PMID- 21026026 TI - Recent trends in electrocardiography. PMID- 21026027 TI - The treatment of rheumatoid arthritis. PMID- 21026028 TI - Effects of continued administration of phenobarbital and diphenylhydantoin. PMID- 21026029 TI - [Not Available]. PMID- 21026030 TI - [Not Available]. PMID- 21026031 TI - [Not Available]. PMID- 21026032 TI - [Not Available]. PMID- 21026033 TI - [Not Available]. PMID- 21026034 TI - [Not Available]. PMID- 21026035 TI - [Not Available]. PMID- 21026036 TI - [Not Available]. PMID- 21026037 TI - [Not Available]. PMID- 21026038 TI - Observations on the utilization of folic acid (vitamin BC) and vitamin BC conjugate by persons with pernicious anemia and macrocytic anemia following gastrectomy. PMID- 21026039 TI - Treatment of malignant testicular neoplasms; analysis of eighty cases. PMID- 21026040 TI - Recurrent parathyroid adenoma; a case report. PMID- 21026041 TI - Diagnosis of spinal angiomas. PMID- 21026043 TI - [Not Available]. PMID- 21026042 TI - [Not Available]. PMID- 21026044 TI - [Not Available]. PMID- 21026045 TI - [Not Available]. PMID- 21026046 TI - A new and simple procedure for developing esophageal voice in the laryngectomized patient. PMID- 21026047 TI - Traumatic loose bodies from the patella. PMID- 21026048 TI - Diverticula of the jejunum; with report of two cases. PMID- 21026049 TI - Rocky Mountain spotted fever. PMID- 21026050 TI - Acute osteomyelitis of the superior maxilla in infants. PMID- 21026051 TI - The clinical significance of hemangiomata of the leg. PMID- 21026052 TI - A study to determine the antibacterial efficiency of combined tyrothricin and sulfadiazine. PMID- 21026053 TI - Rh factor. PMID- 21026054 TI - Vascular injuries in battle casualties. PMID- 21026055 TI - Occupational disease control. PMID- 21026056 TI - Otolaryngologic contacts in dentistry. PMID- 21026057 TI - Mesenteric occlusion treated by Mikulicz type of resection; case report. PMID- 21026058 TI - Ventriculocisternostomy (report of four cases). PMID- 21026059 TI - The role of amino acids in health and disease. PMID- 21026060 TI - [SILICOSIS of the lungs and mediastinal lymph nodes]. PMID- 21026061 TI - Medical care insurance, compulsory or voluntary? PMID- 21026062 TI - Treatment of allergic conditions with pyribenzamine and benadryl. PMID- 21026063 TI - Treatment of undulant fever with streptomycin. PMID- 21026064 TI - Physical examination of school employees with special reference to tuberculosis. PMID- 21026065 TI - Folic acid in the anemias. PMID- 21026066 TI - The diagnosis of malaria. PMID- 21026067 TI - [Not Available]. PMID- 21026069 TI - [Not Available]. PMID- 21026068 TI - [Not Available]. PMID- 21026070 TI - [Not Available]. PMID- 21026071 TI - Brief review of wartime medicine from Pearl Harbor to V-D Day. PMID- 21026072 TI - Manila Bay episode; postscript. PMID- 21026073 TI - Cargo ship as a transport. PMID- 21026075 TI - Malaria control in mobile warfare; Italian campaign 1943-1945. PMID- 21026074 TI - Control of athletes foot. PMID- 21026076 TI - The works of a Corps psychiatrist in the Italian campaign. PMID- 21026077 TI - Pyogenic infection as a complication of ischaemic necrosis of muscle; a report on three cases. PMID- 21026080 TI - MEDICS' BADGE. PMID- 21026079 TI - Notes on certain infectious diseases. PMID- 21026078 TI - A system for an efficient transfusion service in the Army general hospital. PMID- 21026081 TI - SIMPLE tests of nerve trunk injuries. PMID- 21026082 TI - Blood specific gravity determinations in the evaluation and treatment of battle casualties. PMID- 21026083 TI - An improvised colostomy spur crushing device. PMID- 21026084 TI - Splinting metacarpal fractures. PMID- 21026085 TI - Commitment to treatment for syphilis by the premature administration of pencillin. PMID- 21026086 TI - Standard procedures at the Third U.S. Army Air and Railhead Evacuation Holding Unit. PMID- 21026087 TI - Finger exercisers to induce active exercise. PMID- 21026088 TI - NECROSIS following injection of procaine. PMID- 21026089 TI - CRITERIA of satisfactory result of six-month examination of patients treated for syphilis. PMID- 21026090 TI - FUNCTIONS of clinical psychologists in the E.T.O. PMID- 21026091 TI - Contact dermatitis from penicillin with ocular manifestations. PMID- 21026092 TI - Pseudo-spirochaetes in blood. PMID- 21026093 TI - TREATMENT of scabies. PMID- 21026094 TI - Straw mattress dermatitis in Britain associated with rat mite. PMID- 21026095 TI - The 1944 eruption of Vesuvius. PMID- 21026096 TI - The hospital program of the Veterans' Administration. PMID- 21026097 TI - The returning serviceman; how does he stack up physically? PMID- 21026098 TI - Patellar and olecranon bursitis: with the report of an improved operative procedure. PMID- 21026099 TI - Infectious mononucleosis simulating acute appendicitis; report of a case aboard ship. PMID- 21026100 TI - Combat psychiatry; Third United States Army experience. PMID- 21026101 TI - The administration of a small psychiatry center (Z.I.) in a general hospital. PMID- 21026102 TI - The implications of the advanced surgical echelon colostomy. PMID- 21026103 TI - Tuberculous epididymitis in the Army. PMID- 21026104 TI - Physical status of the officer candidate. PMID- 21026105 TI - Congenital anomaly of the sternum-vertical non-fusion; report of two cases. PMID- 21026106 TI - Opportunity in pharmacy. PMID- 21026107 TI - Preliminary report of the use of sulfadiazine bentonite solution in the treatment of external otitis. PMID- 21026108 TI - Studies on wounds of the abdomen and thorax produced by high velocity missiles. PMID- 21026109 TI - [Not Available]. PMID- 21026110 TI - [Not Available]. PMID- 21026111 TI - [Not Available]. PMID- 21026112 TI - [Not Available]. PMID- 21026113 TI - Protection of feet immersed in cold water. PMID- 21026114 TI - Study of 100 cases of abdominal pain in service women. PMID- 21026115 TI - Filariasis among white immigrants in Samoa. PMID- 21026116 TI - Asymptomatic microfilariemia in the Carribbean area. PMID- 21026117 TI - Acute infective jaundice (acute hepatitis); occurrence at a North African base hospital. PMID- 21026118 TI - Treatment of battle casualties resulting from a dive-bombing attack on an ssex class carrier. PMID- 21026119 TI - Radiation sickness in Nagasaki; preliminary report. PMID- 21026120 TI - Suture of the fingernail in crushing injuries. PMID- 21026121 TI - Coccidioidomycosis at U.S.M.C. Air Station, Mohave, California. PMID- 21026122 TI - Action of supernatants from combined growth of Fusarium solani and Pseudomonas aeruginosa against the tubercle bacillus. PMID- 21026123 TI - Susceptibility of serologically typed group A streptococci to penicillin. PMID- 21026124 TI - Electric ophthalmia. PMID- 21026125 TI - Mental health of men discharged under the point system. PMID- 21026126 TI - Suppression of early syphilis by subtherapeutic dosage of penicillin; report of a case. PMID- 21026127 TI - Aids in diagnosing dental pulp diseases. PMID- 21026128 TI - Mercuric cyanide in treatment of periodontal disease. PMID- 21026129 TI - Exostosis of sacrum; report of a case. PMID- 21026130 TI - Meningococcemia with Waterhouse-Friederichsen syndrome. PMID- 21026131 TI - Importance of accuracy in recording of first dental examination; report of unusual case of identification. PMID- 21026132 TI - Multiple infection with intestinal parasites on a naval vessel. PMID- 21026133 TI - Amphibious tractors as medical facilities in the field. PMID- 21026134 TI - Use of the LSV for evacuation and care of amphibious combat casualties. PMID- 21026135 TI - Seabee sickbay. PMID- 21026136 TI - Adjustable back rest for field hospital cot. PMID- 21026137 TI - Arsenical poisoning. PMID- 21026138 TI - Poisoning by barracuda-like fish in the Marianas. PMID- 21026139 TI - Medical research mission to the Soviet Union. PMID- 21026140 TI - Functions and development of a tropical marine laboratory. PMID- 21026141 TI - The purification and crystallization of Clostridium botulinum type A toxin. PMID- 21026142 TI - The isolation and crystallization of tetanal toxin. PMID- 21026143 TI - The effect of the prepartum diet of the cow on the vitamin A reserves of her newborn offspring. PMID- 21026144 TI - The low therapeutic activity of penicillin K relative to that of penicillins F, G, and X, and its pharmacological basis. PMID- 21026145 TI - Direct culture of rheumatic virus. PMID- 21026146 TI - The Lifwynn eye-movement camera. PMID- 21026147 TI - Inactivation of penicillin by zinc salts. PMID- 21026148 TI - A note on staining plasmodia. PMID- 21026149 TI - The fluorescence of radium burns. PMID- 21026151 TI - Transmission of Sarcocystis to swine. PMID- 21026150 TI - A new and effective hemostatic agent. PMID- 21026152 TI - The probable origin of some unusually heavy infections with common sheep hookworm (Bunostomum trigonocephalum). PMID- 21026153 TI - A preliminary study of the occurrence of internal parasites of animals in Mississippi. PMID- 21026154 TI - A new nematode, Longistriata caudabullata, n. sp. (Nematoda: Vianaiinae), from the short-tailed shrew, Blarina brevicauda. PMID- 21026155 TI - The genus Aelurostrongylus Cameron, 1927 (Nematoda: Metastrongylidae), and its relatives; with descriptions of Parafilaroides, gen. nov., and Angiostrongylus gubernaculatus, sp. nov. PMID- 21026156 TI - [Not Available]. PMID- 21026157 TI - [Not Available]. PMID- 21026158 TI - [Not Available]. PMID- 21026159 TI - [Not Available]. PMID- 21026160 TI - [Not Available]. PMID- 21026161 TI - [Not Available]. PMID- 21026162 TI - [Not Available]. PMID- 21026163 TI - [Not Available]. PMID- 21026164 TI - [Not Available]. PMID- 21026165 TI - [Not Available]. PMID- 21026166 TI - [Not Available]. PMID- 21026167 TI - [Not Available]. PMID- 21026169 TI - [Not Available]. PMID- 21026168 TI - [Not Available]. PMID- 21026170 TI - [Not Available]. PMID- 21026171 TI - [Not Available]. PMID- 21026172 TI - [Not Available]. PMID- 21026173 TI - [Not Available]. PMID- 21026174 TI - [Not Available]. PMID- 21026175 TI - [Not Available]. PMID- 21026176 TI - [Not Available]. PMID- 21026177 TI - [Not Available]. PMID- 21026178 TI - [Not Available]. PMID- 21026179 TI - [Not Available]. PMID- 21026180 TI - [Not Available]. PMID- 21026181 TI - [Not Available]. PMID- 21026182 TI - [Not Available]. PMID- 21026183 TI - [Not Available]. PMID- 21026184 TI - [Not Available]. PMID- 21026185 TI - [Not Available]. PMID- 21026186 TI - [Not Available]. PMID- 21026187 TI - [Not Available]. PMID- 21026188 TI - [Not Available]. PMID- 21026189 TI - [Not Available]. PMID- 21026190 TI - [Not Available]. PMID- 21026191 TI - [Not Available]. PMID- 21026192 TI - [Not Available]. PMID- 21026193 TI - [Not Available]. PMID- 21026194 TI - [Not Available]. PMID- 21026195 TI - [Not Available]. PMID- 21026196 TI - [Not Available]. PMID- 21026197 TI - [Not Available]. PMID- 21026198 TI - [Not Available]. PMID- 21026199 TI - [Not Available]. PMID- 21026200 TI - [Not Available]. PMID- 21026201 TI - [Not Available]. PMID- 21026202 TI - [Not Available]. PMID- 21026204 TI - [Not Available]. PMID- 21026203 TI - [Not Available]. PMID- 21026205 TI - [Not Available]. PMID- 21026206 TI - [Not Available]. PMID- 21026207 TI - [Not Available]. PMID- 21026208 TI - [Not Available]. PMID- 21026209 TI - [Not Available]. PMID- 21026210 TI - [Not Available]. PMID- 21026211 TI - [Not Available]. PMID- 21026212 TI - Effect of carbohydrate feeding on the urinary output of amino acid and other metabolites in man. PMID- 21026214 TI - Mechanism of skeletal disuse atrophy. PMID- 21026213 TI - The relationship between cytochrome oxidase and succinic dehydrogenase in the developing chick embryo. PMID- 21026215 TI - Ascorbic acid and tyrosine metabolism. PMID- 21026216 TI - On the formation of acetylcholine by choline acetylase in the nerve axon. PMID- 21026217 TI - Separation of amino acids with the aid of ion exchangers. PMID- 21026218 TI - Influence of iodination on tryptic activity. PMID- 21026219 TI - Analysis of basic organic compounds in biological tissues; estimation of fluorescent compounds. PMID- 21026220 TI - Analysis of basic organic compounds in biological tissues; salt formation with methyl orange. PMID- 21026222 TI - An unidentified factor essential for rat growth. PMID- 21026221 TI - Effect of solvent upon utilization of beta-carotene for vitamin A storage. PMID- 21026223 TI - A nucleoprotein from avian tubercle bacilli. PMID- 21026224 TI - Enzymatic formation of guanine by a reversible phosphorolytic cleavage of ribonucleic acid. PMID- 21026225 TI - Metabolic products of several synthetic antimalarials in the human. PMID- 21026226 TI - Characteristic and sensitive color reaction of SH-compounds. PMID- 21026227 TI - Phosphate exchange in bone using radiophosphorus in vitro. PMID- 21026228 TI - Isolation of brain diphosphoinositide, a new phosphatide containing inositol meta diphosphate as a constituent. PMID- 21026229 TI - Improvements in determinations of carbon monoxide, bromsulphalein, and plasma dyes. PMID- 21026230 TI - Studies of the melting points of gelatin gels. PMID- 21026231 TI - Precise estimation of lysine in the van Slyke-Neill manometric apparatus with a specific decarboxylase. PMID- 21026232 TI - Diet and calcium phosphate deposits in guinea pigs. PMID- 21026233 TI - Cytochrome C-cyanide complex. PMID- 21026234 TI - Analysis of basic organic compounds in biological tissues; ultraviolet spectrophotometry. PMID- 21026235 TI - Effect of hemin proteins on soybean lipoxidase. PMID- 21026236 TI - Amino acids in the production of granulocytes in rats. PMID- 21026237 TI - Effect of level of thyroid activity on response of ovariectomized rats to estrone. PMID- 21026238 TI - Histaminase oxidase. PMID- 21026239 TI - Specificity of pectinesterase of higher plants. PMID- 21026240 TI - Protein fractionation studies on the sera of control and injured dogs. PMID- 21026241 TI - Race, type, and ethnic group in ancient Greece. PMID- 21026242 TI - Chronic sickness in relation to survivorship twenty years later. PMID- 21026243 TI - The relationship between epilepsy and maternal age. PMID- 21026244 TI - Ossicula wormiana. PMID- 21026245 TI - [Not Available]. PMID- 21026246 TI - [Not Available]. PMID- 21026247 TI - [Not Available]. PMID- 21026248 TI - [Not Available]. PMID- 21026249 TI - [Not Available]. PMID- 21026250 TI - [Not Available]. PMID- 21026251 TI - [Not Available]. PMID- 21026252 TI - [Not Available]. PMID- 21026253 TI - [Not Available]. PMID- 21026254 TI - [Not Available]. PMID- 21026255 TI - [Not Available]. PMID- 21026256 TI - [Not Available]. PMID- 21026257 TI - [Not Available]. PMID- 21026258 TI - [Not Available]. PMID- 21026259 TI - [Not Available]. PMID- 21026260 TI - [Not Available]. PMID- 21026261 TI - [Not Available]. PMID- 21026262 TI - The acrylic-amalgam link; a restoration for anterior teeth. PMID- 21026263 TI - Penicillin therapy in dental practice. PMID- 21026264 TI - A controlled, correctable, and physiologically tolerable impression technique. PMID- 21026265 TI - A case report of mouth rehabilitation and restoration of vertical dimension. PMID- 21026266 TI - The use of the desiccating current in treating buccal gingival caries. PMID- 21026267 TI - Pregnancy and tooth decay. PMID- 21026268 TI - Dental health progress in Chile. PMID- 21026269 TI - School health policies applied to dental health. PMID- 21026270 TI - [Not Available]. PMID- 21026271 TI - Dental education; its philosophy, its support and its future as seen through the eyes of this University. PMID- 21026273 TI - Action of cystine on bones and teeth of young dogs. PMID- 21026272 TI - Would I study dentistry if I had it to do over again? PMID- 21026274 TI - Hospitals as teaching agencies in dental education. PMID- 21026275 TI - Toothbrushes, toothbrush materials and design. PMID- 21026276 TI - Oral surgery in amphibious warfare. PMID- 21026277 TI - Liners for dentures. PMID- 21026278 TI - The normal and the abnormal labial frenum; clinical differentiation. PMID- 21026279 TI - Medical and dental care in prepayment medical care organizations. PMID- 21026280 TI - Amalgam; inconsistencies in its use in restorations. PMID- 21026281 TI - Treatment of Vincent's infection. PMID- 21026283 TI - [Not Available]. PMID- 21026282 TI - Dental treatment for veterans. PMID- 21026284 TI - [Not Available]. PMID- 21026286 TI - Osteomyelitis of mandible following removal of a tooth. PMID- 21026285 TI - Jaw injuries in a prisoner of war hospital, 1943-45. PMID- 21026288 TI - Some problems in daily practice and how to solve them. PMID- 21026287 TI - Salivary calculus in Wharton's duct. PMID- 21026289 TI - Fluorine in medicine. PMID- 21026290 TI - Acrylic denture resins. PMID- 21026291 TI - [Not Available]. PMID- 21026292 TI - [Not Available]. PMID- 21026293 TI - [Not Available]. PMID- 21026294 TI - [Not Available]. PMID- 21026295 TI - [Not Available]. PMID- 21026296 TI - [Not Available]. PMID- 21026298 TI - STUDY of proposals for the registration of dental technicians and laboratories. PMID- 21026297 TI - [Not Available]. PMID- 21026299 TI - Denture service diagnosis. PMID- 21026300 TI - Investigations on the importance of bacterial allergy for the development of cutaneous infections due to staphylococci. PMID- 21026301 TI - [Not Available]. PMID- 21026302 TI - Parallel striae of the lumbar area as a sign of spina bifida occulta. PMID- 21026303 TI - Rheumatic fever eruptions. PMID- 21026304 TI - Two types of joint complaints by antisyphilitic treatment. PMID- 21026305 TI - Effects of sulphur on the skin; clinical and experimental observations with an aqueous solution of polythionic acids (polythiosol). PMID- 21026306 TI - [Not Available]. PMID- 21026307 TI - [Not Available]. PMID- 21026308 TI - [Not Available]. PMID- 21026309 TI - [Not Available]. PMID- 21026310 TI - [Not Available]. PMID- 21026311 TI - [Not Available]. PMID- 21026312 TI - [Not Available]. PMID- 21026313 TI - [Not Available]. PMID- 21026314 TI - [Not Available]. PMID- 21026315 TI - [Not Available]. PMID- 21026316 TI - [Not Available]. PMID- 21026317 TI - [Not Available]. PMID- 21026318 TI - Skin changes in rabbits' ears produced by repeated intracutaneous injections of diphtheria toxin. PMID- 21026319 TI - Penicillin therapy in gonorrhea, with special reference to protraction of the penicillin effect. PMID- 21026320 TI - False positive seroreactions for syphilis in connection with erythema nodosum. PMID- 21026321 TI - Chronic hereditary edema of extremities (Milroy's disease). PMID- 21026322 TI - On the content of acid phosphatase in ejaculate and prostatic secretion. PMID- 21026323 TI - Extraordinary hypersensitiveness to cell wool. PMID- 21026325 TI - Adenoma sebaceum. PMID- 21026324 TI - A glomus tumour in situ. PMID- 21026326 TI - Exanthema after sulfathiazol and exposure to light. PMID- 21026327 TI - Acquired syphilis in a 15 month old child. PMID- 21026328 TI - Tardy secondary ecthymatiform, partially corymbose syphilid, developed during specific antisyphilitic treatment. PMID- 21026329 TI - Trichophytosis with kerion on the scalp, and secondary trichophytids with peculiar localisation. PMID- 21026330 TI - A case of herpes zoster in a 5 1/2 month old child. PMID- 21026331 TI - Exanthema resembling lichen ruber during treatment with neosalvarsan. PMID- 21026332 TI - A case for diagnosis (Behcet's syndrome?). PMID- 21026333 TI - Necrobiosis lipoidica (diabeticorum?). PMID- 21026334 TI - Ulcerous carcinoma in the pubis region simulating gummous changes in a patient with syphilis of long standing. PMID- 21026335 TI - Sulpha addition treatment combined with pyretotherapy in gonorrhea during pregnancy. PMID- 21026337 TI - A case of von Recklinghausen's neurofibromatosis. PMID- 21026336 TI - Generalized allergic Brucella exanthema in a veterinary surgeon. PMID- 21026338 TI - [Not Available]. PMID- 21026339 TI - Investigation into falsely positive serological syphilis reactions. PMID- 21026340 TI - Pseudo-sarcome surlupique. PMID- 21026341 TI - On a complex etiology of erythema nodosum; with reference to the results of an odontologic study. PMID- 21026342 TI - Epithelioma; report on 1,742 treated patients. PMID- 21026343 TI - Poikiloderma atrophicans vasculare Jacobi; cutaneous changes typical of this disease in a patient with late meningovascular neurosyphilis. PMID- 21026344 TI - Experimental study on the absorption of amyloid in localized amyloidosis by skin grafting. PMID- 21026345 TI - Unusual pigmentation developing after prolonged suppressive therapy with quinacrine hydrochloride. PMID- 21026346 TI - Immunization therapy for lichen planus. PMID- 21026348 TI - Micropapular tuberculid in the Negro. PMID- 21026347 TI - Epidermal sensitivity to penicillin. PMID- 21026350 TI - Tinea capitis, cured with local applications. PMID- 21026349 TI - DDT in the treatment of scabies, larva migrans and pediculosis pubis. PMID- 21026352 TI - Pustuloulcerative (frambesiform) syphilid. PMID- 21026351 TI - Vitamin A deficiency producing follicular hyperkeratosis. PMID- 21026353 TI - Alopecia cicatrisata. PMID- 21026354 TI - Chronic lymphatic leukemia; cutaneous lesions following irradiation. PMID- 21026355 TI - Multiple neurofibromatosis with sarcoma (now excised). PMID- 21026356 TI - Arteriosclerotic ulcer of the leg. PMID- 21026357 TI - Pemphigus, apparently favorable response to sulfadiazine therapy. PMID- 21026358 TI - Alopecia cicatrisata. PMID- 21026360 TI - Late effects of scalping. PMID- 21026359 TI - Residual eruption following acute dermatitis from oil. PMID- 21026361 TI - Contact dermatitis, caused by zinc chromate paint. PMID- 21026362 TI - Contact dermatitis due to frequent contact with thinner. PMID- 21026363 TI - Tattoo-like staining following occupational dermatitis. PMID- 21026365 TI - Atopic eczema. PMID- 21026364 TI - Dermatitis due to soap. PMID- 21026366 TI - Multiple pigmented hairy nevi (melanocarcinoma?). PMID- 21026367 TI - Hydrocystoma. PMID- 21026368 TI - A case for diagnosis (fibrosarcoma?). PMID- 21026369 TI - Lichen nitidus. PMID- 21026370 TI - A case for diagnosis (microaerophilic ulcer?). PMID- 21026371 TI - Epidermodysplasia verruciformis. PMID- 21026372 TI - Acrodermatitis chronica atrophicans with angiosarcomas. PMID- 21026373 TI - A case for diagnosis (dermatitis medicamentosa). PMID- 21026374 TI - Tertiary syphilis. PMID- 21026375 TI - A case for diagnosis (leukemia cutis?). PMID- 21026376 TI - Parapsoriasis. PMID- 21026377 TI - A case for diagnosis (tuberculosis verrucosa cutis?). PMID- 21026378 TI - Chronic dermatophytosis of the feet and erythema annulare of the face and neck. PMID- 21026379 TI - Hodgkin's disease. PMID- 21026380 TI - [Not Available]. PMID- 21026381 TI - Congenital defect of hair. PMID- 21026382 TI - Lupus vulgaris, treated with promizole (4,2-diaminophenyl-5-thiazolesulfone). PMID- 21026383 TI - A case for diagnosis (seborrheic dermatitis?). PMID- 21026384 TI - [Not Available]. PMID- 21026385 TI - [Not Available]. PMID- 21026386 TI - [Not Available]. PMID- 21026387 TI - The genesis of some Scandinavian species of Calamagrostis. PMID- 21026388 TI - The effect of heterozygosity on variability and vigour. PMID- 21026389 TI - On heterosis effects in Triticum vulgare. PMID- 21026390 TI - The thresholds of colchicine action in barley, rye, diploid oat, and in their artificial tetraploids. PMID- 21026391 TI - A possible explanation of increased vigour in sibpollinated later generations after self-fertilisation. PMID- 21026392 TI - [Not Available]. PMID- 21026393 TI - [Not Available]. PMID- 21026394 TI - [Not Available]. PMID- 21026395 TI - [Not Available]. PMID- 21026396 TI - [Not Available]. PMID- 21026397 TI - [Not Available]. PMID- 21026398 TI - [Not Available]. PMID- 21026399 TI - Anti-anemic properties of thymine. PMID- 21026401 TI - Primary polyoythemia; remissions induced by therapy with radiophosphorus. PMID- 21026400 TI - Acute hemolytic anemia and hemoglobinuria following sulfadiazine medication. PMID- 21026402 TI - Prognosis in the neurologic manifestations of pernicious anemia. PMID- 21026403 TI - Standardization of the Quick prothrombin test; with reference to the statistical significance of variations in the prothrombin concentration with use of a stable thromboplastin of high potency. PMID- 21026404 TI - Individual blood differences in relation to pregnancy, with special reference to the pathogenesis of preeclamptic toxemia. PMID- 21026405 TI - Hematologic effects of splenectomy in Still-Chauffard-Felty syndrome a report of two cases. PMID- 21026406 TI - European spas through the centuries. PMID- 21026407 TI - Rise and fall of the American spa. PMID- 21026408 TI - Towards a renaissance of the American spa. PMID- 21026410 TI - Administration in a hospital in China. PMID- 21026409 TI - Haemolytic disease of the newborn. PMID- 21026411 TI - The preparation of a potent toxin of Shigella dysenteriae (Shiga) on a semi synthetic medium and its use for the preparation of an alum-precipitated toxoid. PMID- 21026413 TI - Semliki Forest virus; propagation of the virus in developing chick embryos. PMID- 21026412 TI - Studies on the reversibility of the antigen-antibody reaction; correlation between the effects of homologous polysaccharide-on capsular swelling and infectivity of sensitized pneumococci. PMID- 21026414 TI - The behaviour of platelets in anaphylactic and peptone shock. PMID- 21026415 TI - Studies in human malaria; the preparation of vaccines and suspensions containing plasmodia. PMID- 21026416 TI - Precipitin-production in chickens; studies on the in vitro rise of the interfacial titers and the formation of precipitins. PMID- 21026417 TI - Comparative sensitivity of the extraneural and intracerebral neutralization tests in following the antibody response in man to vaccination with western equine encephalomyelitis virus. PMID- 21026419 TI - Ocular effects of radiant energy. PMID- 21026418 TI - Hostile dependent behavior in rehabilitation of vetrans with psychoneuroses and of the industrially injured with a psychologically protracted convalescence. PMID- 21026420 TI - A health program for the Merchant Marine. PMID- 21026421 TI - Pre-placement x-ray examination of the lower back. PMID- 21026422 TI - The treatment of injuries to the hand, with particular reference to nerve and tendon repair. PMID- 21026423 TI - Psychoneurosis; its impact on industry; are psychoneurotics employable? PMID- 21026424 TI - PSYCHONEUROSIS in industry. PMID- 21026425 TI - Industrial relations values in industrial medicine. PMID- 21026426 TI - Psychologically hazardous occupations. PMID- 21026427 TI - On the job. PMID- 21026428 TI - Etiology of dental sequelae. PMID- 21026429 TI - Sunburn, and industrial absenteeism. PMID- 21026430 TI - [Not Available]. PMID- 21026431 TI - [Not Available]. PMID- 21026432 TI - Malaria in the Irwin Canal area, Mysore State. PMID- 21026433 TI - Malaria in the Irwin Canal area, Mysore State. PMID- 21026434 TI - On the adult bionomics of some Indian anophelines; with special reference to malaria control by pyrethum-spraying. PMID- 21026435 TI - On the bionomics of Anopheles culcifacies Giles; the behaviour of adults. PMID- 21026436 TI - On the bionomics of Anopheles culicifacies Giles; hypothesis of the races of A. culicifacies. PMID- 21026437 TI - The behaviour of Anopheles fluviatilis; the behaviour of gravid females. PMID- 21026439 TI - Dry leaf packing for the control of mosquito breeding. PMID- 21026438 TI - False economy in the planning and conduct of antimalaria campaigns. PMID- 21026440 TI - [Not Available]. PMID- 21026441 TI - [Not Available]. PMID- 21026442 TI - [Not Available]. PMID- 21026443 TI - [Not Available]. PMID- 21026444 TI - [Not Available]. PMID- 21026445 TI - A rare form of cold-agglutination. PMID- 21026446 TI - On the cause of post-syncopal oliguria. PMID- 21026447 TI - On the occurrence in human serum of yellow substances different from bilirubin and carotenoids. PMID- 21026448 TI - Bilirubin and unrobilinoid contents of human bile. PMID- 21026449 TI - Prognosis of late syphilitic cardiovascular lesions. PMID- 21026450 TI - Prognostic significance of the electrocardiogram in late syphilitic cardiovascular lesions. PMID- 21026451 TI - [Not Available]. PMID- 21026452 TI - On the neurocirculatory syndrome (neurocirculatory asthenia) in soldiers. PMID- 21026453 TI - On adrenaline determination according to the fluorescence method. PMID- 21026454 TI - Regarding the vitamin C standard in various groups of population in Finland in the years of war 1941-1943. PMID- 21026455 TI - Treatment of parathyroid tetany with vitamin D2. PMID- 21026456 TI - Panmyelopathy (panmyelophthisis). PMID- 21026457 TI - Studies on the serum proteins in hepatitis; the relation between serum albumin and serum globulin. PMID- 21026458 TI - Diabetes mellitus and pulmonary tuberculosis. PMID- 21026459 TI - The cytological diagnosis of gastritis. PMID- 21026460 TI - Contributions to the symptomatology of amyotonia congenita (infantile spinal muscular atrophy). PMID- 21026461 TI - Is digestive leukocytosis a reality? PMID- 21026462 TI - The influence of vitamin C on the effect of thyrotropic hormone. PMID- 21026463 TI - [Not Available]. PMID- 21026464 TI - On the effect of combined administration of methylthiouracil and iodine on the thyroids of normal rats. PMID- 21026465 TI - Auricular standstill. PMID- 21026466 TI - Arthralgia due to nervous causes. PMID- 21026467 TI - Titration with Weichbrodt's reagent of serum, particularly in the case of gall liver diseases. PMID- 21026468 TI - A peculiar conduction disturbance, persisting latently after recovery from complete heart block and disclosed only by electrocardiography following exercise. PMID- 21026470 TI - On hereditary, non-hemolytic bilirubinemia. PMID- 21026469 TI - Infections with leukopenia treated with sulfa compounds. PMID- 21026471 TI - [Not Available]. PMID- 21026472 TI - [Not Available]. PMID- 21026473 TI - [Not Available]. PMID- 21026474 TI - [Not Available]. PMID- 21026475 TI - [Not Available]. PMID- 21026476 TI - [Not Available]. PMID- 21026477 TI - [Not Available]. PMID- 21026478 TI - [Not Available]. PMID- 21026479 TI - [Not Available]. PMID- 21026480 TI - [Not Available]. PMID- 21026481 TI - [Not Available]. PMID- 21026483 TI - [Not Available]. PMID- 21026482 TI - [Not Available]. PMID- 21026484 TI - [Not Available]. PMID- 21026485 TI - [Not Available]. PMID- 21026486 TI - [Not Available]. PMID- 21026487 TI - [Not Available]. PMID- 21026488 TI - Nutritional macrocytic anemia, especially in pregnancy; response to a substance in liver other than that effective in pernicious anemia. PMID- 21026489 TI - Hookworm infection in American troops in Assam and Burma. PMID- 21026490 TI - Rutin; a new drug for the treatment of increased capillary fragility. PMID- 21026491 TI - Acute ethylene glycol poisoning; a clinico-pathologic report of eighteen fatal cases. PMID- 21026492 TI - Successful combined treatment of penicillin-resistant gonorrhea. PMID- 21026493 TI - Meningoccus endocarditis. PMID- 21026494 TI - Azotemia in gastro-intestinal bleeding; the ingestion of shed blood in humans. PMID- 21026495 TI - A study of the effect of bleeding and of repeated blood donation on serologic tests for syphilis. PMID- 21026496 TI - Hereditary hemorrhagic telangiectasia. PMID- 21026497 TI - Bronchopulmonary geotrichosis. PMID- 21026498 TI - The penetration of antibacterial substances into ischemic, inflammatory tissue; with a consideration of their use in shock of bacterial origin. PMID- 21026499 TI - Acute pleurisy as a dehydration phenomenon in diabetic precoma. PMID- 21026500 TI - On the expectorant action of volatile oils. PMID- 21026501 TI - Alterations in capillary permeability in meningeal irritations; an aid to differential diagnosis. PMID- 21026502 TI - Sulfonamide urolithiasis. PMID- 21026503 TI - Roentgenologic changes observed in tropical diseases. PMID- 21026504 TI - [Not Available]. PMID- 21026506 TI - [Not Available]. PMID- 21026505 TI - [Not Available]. PMID- 21026507 TI - A reticulocitose na tuberculose pulmonar cronica. PMID- 21026508 TI - [Not Available]. PMID- 21026509 TI - [Not Available]. PMID- 21026510 TI - [Not Available]. PMID- 21026511 TI - [Not Available]. PMID- 21026512 TI - [Not Available]. PMID- 21026513 TI - [Not Available]. PMID- 21026514 TI - [Not Available]. PMID- 21026515 TI - [Not Available]. PMID- 21026516 TI - [Not Available]. PMID- 21026517 TI - [Not Available]. PMID- 21026518 TI - [Not Available]. PMID- 21026519 TI - [Not Available]. PMID- 21026520 TI - Penicillin treatment of Erb's syphilitic spinal spastic paraplegia; report of four cases, one with autopsy. PMID- 21026521 TI - Concerning the function and origin of the reticular zone of the adrenal cortex; hyperplasia in the adrenogenital syndrome. PMID- 21026522 TI - Cerebral involvement in schistosomiasis japonica. PMID- 21026523 TI - Cutaneous distribution of peripheral nerves in rhesus monkeys as determined by the electrical skin resistance method. PMID- 21026524 TI - Importance of breast feeding. PMID- 21026525 TI - Diagnosis of pulmonary tuberculosis. PMID- 21026526 TI - Anesthesiology. PMID- 21026527 TI - Report of physical examinations for pension purposes. PMID- 21026528 TI - [Not Available]. PMID- 21026529 TI - [Not Available]. PMID- 21026530 TI - [Not Available]. PMID- 21026531 TI - [Not Available]. PMID- 21026532 TI - [Not Available]. PMID- 21026533 TI - [Not Available]. PMID- 21026534 TI - [Not Available]. PMID- 21026535 TI - [Not Available]. PMID- 21026536 TI - [Not Available]. PMID- 21026537 TI - [Not Available]. PMID- 21026538 TI - [Not Available]. PMID- 21026539 TI - [Not Available]. PMID- 21026540 TI - [Not Available]. PMID- 21026541 TI - [Not Available]. PMID- 21026542 TI - [Not Available]. PMID- 21026543 TI - [Not Available]. PMID- 21026544 TI - The use and efficacy of sulfonamides and penicillin. PMID- 21026545 TI - Gastro-jejuno-colic fistula; a case report. PMID- 21026546 TI - Surgery in the treatment of acute massive hemorrhage from peptic ulcer. PMID- 21026547 TI - Mycosis fungoides; report of case with clinical and post-mortem findings. PMID- 21026548 TI - Kaposi's varicelliform eruption. PMID- 21026549 TI - [Not Available]. PMID- 21026550 TI - [Not Available]. PMID- 21026551 TI - [Not Available]. PMID- 21026552 TI - [Not Available]. PMID- 21026553 TI - [Not Available]. PMID- 21026554 TI - [Not Available]. PMID- 21026555 TI - [Not Available]. PMID- 21026556 TI - [Not Available]. PMID- 21026557 TI - [Not Available]. PMID- 21026558 TI - [Not Available]. PMID- 21026559 TI - [Not Available]. PMID- 21026560 TI - [Not Available]. PMID- 21026561 TI - Some observations on the surgery of the hand. PMID- 21026562 TI - Some experiences with penicillin. PMID- 21026563 TI - A case of periduodenitis with duodenal stenosis and traction diverticula. PMID- 21026564 TI - Some points in surgery of the thyroid gland. PMID- 21026565 TI - Vitamin A and night vision. PMID- 21026566 TI - Ultra-violet therapy in cases of leucoderma. PMID- 21026567 TI - The relation of arterial blood pressure to successive pregnancies among a rural population in Ceylon. PMID- 21026568 TI - Eosinophilia and some peculiarly staining leucocytes. PMID- 21026569 TI - Ordinary water in place of distilled water in saline transfusion in cholera. PMID- 21026570 TI - A copper sulphate flotation method for the examination of E. histolytica cysts. PMID- 21026571 TI - Notes on a simple technique of splenic culture at the post-mortem table. PMID- 21026572 TI - Acute intussusception due to an inverted Meckel's diverticulum. PMID- 21026574 TI - Two unusual cases of cerebral malaria. PMID- 21026573 TI - Treatment of human anthrax with penicillin. PMID- 21026575 TI - The organization and work of an anatomy department. PMID- 21026576 TI - The Wassermann positive rate of cases from hospitals and venereal clinics of Calcutta in 1939, 1943, 1944 and 1945. PMID- 21026577 TI - A note on the spread of cholera infection through aerated drinks. PMID- 21026578 TI - Is the venereal disease control program in danger? PMID- 21026580 TI - Florida study of child health services. PMID- 21026579 TI - A history of medicine in Duval County. PMID- 21026581 TI - Rehabilitation; a medical challenge. PMID- 21026582 TI - Medicine in the postwar world. PMID- 21026583 TI - The treatment of diabetes mellitus. PMID- 21026584 TI - [Not Available]. PMID- 21026585 TI - [Not Available]. PMID- 21026587 TI - [Not Available]. PMID- 21026586 TI - [Not Available]. PMID- 21026588 TI - [Not Available]. PMID- 21026589 TI - [Not Available]. PMID- 21026590 TI - [Not Available]. PMID- 21026591 TI - [Not Available]. PMID- 21026592 TI - Some notes on the pharmacology of penicillin. PMID- 21026593 TI - Headache mechanisms. PMID- 21026594 TI - Treatment in asphyxia neonatorum. PMID- 21026595 TI - Placental infarcts. PMID- 21026596 TI - A case of rupture of the supraspinatus tendon. PMID- 21026597 TI - Constipation. PMID- 21026598 TI - The present status of penicillin therapy of syphilis. PMID- 21026599 TI - Chemotherapy of chronic suppurative diseases of the lungs and pleura. PMID- 21026600 TI - A case of uterine atony requiring a large amount of blood and plasma. PMID- 21026601 TI - Proposed venereal disease control program. PMID- 21026602 TI - [Not Available]. PMID- 21026603 TI - [Not Available]. PMID- 21026605 TI - [Not Available]. PMID- 21026604 TI - [Not Available]. PMID- 21026606 TI - [Not Available]. PMID- 21026607 TI - [Not Available]. PMID- 21026608 TI - [Not Available]. PMID- 21026609 TI - [Not Available]. PMID- 21026610 TI - [Not Available]. PMID- 21026611 TI - ANTIBACTERIAL substances in green plants. PMID- 21026612 TI - The role of the roentgenologist in the diagnosis of lesions of the upper gastro intestinal tract. PMID- 21026613 TI - What labor expects from medicine. PMID- 21026614 TI - [Not Available]. PMID- 21026615 TI - [Not Available]. PMID- 21026616 TI - [Not Available]. PMID- 21026617 TI - [Not Available]. PMID- 21026619 TI - PRIMARY dysmenorrhea. PMID- 21026618 TI - [Not Available]. PMID- 21026620 TI - [Not Available]. PMID- 21026621 TI - [Not Available]. PMID- 21026622 TI - [Not Available]. PMID- 21026623 TI - [Not Available]. PMID- 21026624 TI - [Not Available]. PMID- 21026625 TI - [Not Available]. PMID- 21026626 TI - [Not Available]. PMID- 21026627 TI - [Not Available]. PMID- 21026628 TI - [Not Available]. PMID- 21026629 TI - [Not Available]. PMID- 21026630 TI - [Not Available]. PMID- 21026632 TI - [Not Available]. PMID- 21026631 TI - [Not Available]. PMID- 21026633 TI - [Not Available]. PMID- 21026634 TI - [Not Available]. PMID- 21026635 TI - [Not Available]. PMID- 21026636 TI - [Not Available]. PMID- 21026637 TI - [Not Available]. PMID- 21026638 TI - [Not Available]. PMID- 21026639 TI - [Not Available]. PMID- 21026640 TI - [Not Available]. PMID- 21026641 TI - [Not Available]. PMID- 21026642 TI - [Not Available]. PMID- 21026643 TI - [Not Available]. PMID- 21026644 TI - [Not Available]. PMID- 21026646 TI - [Not Available]. PMID- 21026645 TI - [Not Available]. PMID- 21026647 TI - [Not Available]. PMID- 21026648 TI - [Not Available]. PMID- 21026649 TI - [Not Available]. PMID- 21026650 TI - [Not Available]. PMID- 21026651 TI - [Not Available]. PMID- 21026652 TI - [Not Available]. PMID- 21026653 TI - [Not Available]. PMID- 21026654 TI - [Not Available]. PMID- 21026655 TI - The Canadian Intern Board. PMID- 21026656 TI - Infantile diarrhoea. PMID- 21026657 TI - The use of pituitary extract in obstetrics. PMID- 21026658 TI - [Not Available]. PMID- 21026659 TI - Liver function tests. PMID- 21026660 TI - [Not Available]. PMID- 21026661 TI - [Not Available]. PMID- 21026662 TI - [Not Available]. PMID- 21026663 TI - [Not Available]. PMID- 21026664 TI - MEDICAL preparation of troops for redeployment through the Assembly Area Command. PMID- 21026665 TI - Homologous serum jaundice following plasma. PMID- 21026666 TI - Positioning for x-ray of perforating and graze fractures. PMID- 21026667 TI - Traumatic shock. PMID- 21026668 TI - A method of shading clear acrylic. PMID- 21026669 TI - An improvised hand exerciser. PMID- 21026671 TI - An adaptation of the Sheard-Sanford hemoglobin method using improvised pipettes. PMID- 21026670 TI - The role of hyperhydrosis in trench foot. PMID- 21026673 TI - Direct duplication of roentgenograms by artificial solarization. PMID- 21026672 TI - Diphtheritic polyneuropathy. PMID- 21026674 TI - Venereal diseases in a theater of operations. PMID- 21026675 TI - A suggestion for treatment of Vincent's infection of the tonsils. PMID- 21026676 TI - A simple water softener. PMID- 21026677 TI - Nutritional deficiencies associated with inadequate protein diets. PMID- 21026678 TI - Hypertraumatism relieved by acrylic appliance. PMID- 21026679 TI - Intravenous stand for use on litter. PMID- 21026680 TI - Glass syringe as aid in application of sulphanilamide powder. PMID- 21026681 TI - Balanced skeletal traction for fractures of the humerus. PMID- 21026682 TI - Electric dental water heater. PMID- 21026683 TI - Penicillin in the treatment of diphtheria and the diphtheria carrier state. PMID- 21026684 TI - FOLLOW-UP results after penicillin therapy of early syphilis. PMID- 21026685 TI - [Not Available]. PMID- 21026686 TI - [Not Available]. PMID- 21026687 TI - [Not Available]. PMID- 21026688 TI - [Not Available]. PMID- 21026689 TI - [Not Available]. PMID- 21026690 TI - [Not Available]. PMID- 21026691 TI - Physical anthropology; a biological science. PMID- 21026692 TI - Proteins, the machines of life. PMID- 21026693 TI - The development of optical instruments. PMID- 21026694 TI - SCIENCE and tropical warfare; the tropical scientific section. PMID- 21026695 TI - Haemagglutination by mumps virus; relationship to Newcastle disease and influenza viruses. PMID- 21026696 TI - Silica gel for the preservation of plant material. PMID- 21026697 TI - A synthetic urethane as a substitute for eserine. PMID- 21026698 TI - A contribution to the chromosome morphology of hard wheat. PMID- 21026699 TI - Absorption spectrum of haemoglobin in solution and in a suspension of red blood corpuscles. PMID- 21026700 TI - Chemical transformations as a source of energy for the mobility of Trypanosoma equiperdum. PMID- 21026701 TI - Susceptibility of intestine epithelium in males and females of Drosophila melanogaster to the noxious effect of lactic acid. PMID- 21026702 TI - On the solubility of boron compounds in the plant. PMID- 21026703 TI - Induction of tympanic membrane in Bombina bombina and Pelobates fuscus. PMID- 21026704 TI - On the poisoning of catalysts. PMID- 21026705 TI - A method for diagnosticating grain toxic as a result of its having overwintered in the field. PMID- 21026706 TI - Viability, rate of growth and morphology of carps of different genotypes as affected by rearing conditions. PMID- 21026707 TI - [Not Available]. PMID- 21026708 TI - On a defensive reaction of the plant cell; a contribution to the comparative pharmacology of sulphonamides. PMID- 21026709 TI - Time of determination of a tumor in the process of its induction with 3:4 benzpyrene. PMID- 21026710 TI - On the taxonomic position of the genera Acanthocheilonema Cobbold and Molinema Freitas et Lent within the system of nematodes. PMID- 21026711 TI - Concentration isotherms of catalyst poisoning. PMID- 21026712 TI - Bacteriostatic substances of animal origin. PMID- 21026713 TI - On the growth hormones in a diseased plant. PMID- 21026714 TI - Tyrosinase enzyme in the agent of the black bacteriosis of cereals. PMID- 21026715 TI - Effect of sun radiation upon body temperature of certain littoral animals. PMID- 21026716 TI - Absolute sensitivity of the eye in infra-red spectrum. PMID- 21026717 TI - On the reduction of orthodinitrobenzene in green plants; on the mechanism of photosynthesis. PMID- 21026718 TI - Influence of calcium chloride upon the course of histogenetic processes in Anura. PMID- 21026719 TI - A contribution to the histophysiology of capillaries. PMID- 21026720 TI - Daylength as a factor decisive for the possibility of the existence of a species. PMID- 21026721 TI - Determination of the isoelectric point of virus proteins by the staining technique. PMID- 21026722 TI - Explantation of eye rudiments. PMID- 21026723 TI - On the discovery of Palaeacariformes (Acarina) in the USSR. PMID- 21026724 TI - Colour vision as affected by electrotonus. PMID- 21026725 TI - Production of the original species of the Chile autotriploid Solanum maglia Schlechtd. at Pamir. PMID- 21026726 TI - Influence of salinity on the eggs of Coregonus migratorius Georgi. PMID- 21026727 TI - Studies on the physiology of the germination of pollen; mutual stimulation in the germination of pollen grains. PMID- 21026728 TI - Interaction between roots and soil colloids as a problem of mineral nutrition of plants; role of the root system. PMID- 21026729 TI - Regulation processes in the metamorphosis of insects; self-differentiation of the wing in butterflies. PMID- 21026731 TI - On the structure of the principal scattering line and the nature of continuous radiation. PMID- 21026730 TI - On the taxonomic position of Haematotrephus fodiens Linton, 1928, within the system of trematodes. PMID- 21026732 TI - On the reduction of orthodinitrobenzene in green plants; on the theory of regulation of protein exchange in plants. PMID- 21026733 TI - A gravimetrical method for determining the activity of growth substances. PMID- 21026734 TI - Transplantation as applied to the study of nutrition of different plant species. PMID- 21026736 TI - Influence of lithium chloride upon histogenetic processes in Amura. PMID- 21026735 TI - Explanation of the rudiments of skin epidermis and neural plate. PMID- 21026737 TI - On the effect of heteroauxine upon cells of diseased plant. PMID- 21026738 TI - Mosaic on Leguminosae. PMID- 21026739 TI - Chemical methods for restoring the regenerative capacity of limbs in tadpoles. PMID- 21026740 TI - Comparative data on the development of reproductive organs in Eurygaster integriceps Put. in the plains of the south of the USSR and in Uzbekistan. PMID- 21026741 TI - On the theory of the characteristic frequencies of polyatomic molecules. PMID- 21026742 TI - Sensitivity of Paramaecium caudatum to toxic agents at various stages of ontogenesis. PMID- 21026743 TI - Growth of roots as stimulated by certain organic acids. PMID- 21026744 TI - On the nature of the inhibitory effect of lens upon lens regeneration in Triton. PMID- 21026745 TI - A new endoparasitic mollusc Parenteroxenos dogieli,nov.gen.,nov.sp. PMID- 21026746 TI - Universal variables in the boundary layer theory. PMID- 21026747 TI - Sensation elements for hearing and touch. PMID- 21026748 TI - Histophysiology of the mesothelium of the serosa of spleen and testis. PMID- 21026749 TI - Influence of phytoacides upon paracholeraic vibrios. PMID- 21026750 TI - Variation in the thermotaxis optimum of rodents as dependent on pregnancy. PMID- 21026751 TI - Regeneration of extremities in Periplaneta orientalis. PMID- 21026752 TI - Electron microscope and investigation of the structure of ceramic materials. PMID- 21026753 TI - Activation of catalase by biogenic stimulants. PMID- 21026754 TI - Intensity of fixation of atmospheric nitrogen by Azotobacter on different sources of carbon. PMID- 21026755 TI - Diffusion and molecular weight of lysozyme. PMID- 21026756 TI - Skin respiration in Carassius carassius. PMID- 21026757 TI - Phagocytic activity of leucocytes as affected by serums containing leucocytic trephones. PMID- 21026758 TI - On the influence of estrogens upon the thyrotropic reaction. PMID- 21026759 TI - On some simplest processes of organization of eye and brain rudiments in urodelan embryos. PMID- 21026760 TI - Spectrum sensitivity of the three receptors of the eye. PMID- 21026761 TI - On the relation between the induction period and the chemism of a reaction. PMID- 21026762 TI - A procedure ensuring the preservation of vitamin C in leaves of gladiolus prepared for storage. PMID- 21026763 TI - Concentration of vitamin C in certain plant species of central Asia. PMID- 21026764 TI - Regeneration of muscles in Mammalia. PMID- 21026766 TI - Some new data on the status of the genus Myennis R.D. (Diptera, Otitidae). PMID- 21026765 TI - Seasonal fluctuation in the frequency of black hamsters. PMID- 21026767 TI - A contribution to the knowledge of the biological cycle of Capillaria mucronata (Molin, 1858), a nematode of the bladder of sable, marten and mink. PMID- 21026768 TI - The effect of colchicine on rice. PMID- 21026769 TI - Chromosome number in Cassia sophera Linn. PMID- 21026770 TI - Chromosome numbers in Sesbania spp. PMID- 21026771 TI - Refection producing bacterium. PMID- 21026772 TI - Hair ball in the stomach of a calf. PMID- 21026773 TI - Latex-tube areas of the roots and leaves of the Russian dandelion. PMID- 21026774 TI - Some aspects of the aerial dissemination of spores, with special reference to conidia of Sclerotinia laxa. PMID- 21026775 TI - Standards of length. PMID- 21026776 TI - Cinnamon-leaf oil. PMID- 21026777 TI - Soap gels in non-aqueous media. PMID- 21026778 TI - USE of DDT and 666 as insecticides against grain pests; the persistence of toxicity of DDT and 666 applied in wall washes. PMID- 21026779 TI - USE of DDT and 666 as insecticides against grain pests; DDT and 666 as sterilisants of floor debris in grain storage sheds. PMID- 21026781 TI - Crystalline thyroxine from Indian cattle thyroid glands. PMID- 21026782 TI - The diseases of newborn lambs with special emphasis on bacteriopathology. PMID- 21026780 TI - The isolation of thyroxine and thyroxine-concentrates from Indian thyroid glands. PMID- 21026783 TI - A synthetic medium for microbiological assay of riboflavin, pantothenic acid, biotin, nicotinic acid, pyridoxine and polic acid. PMID- 21026784 TI - Vitamins required by swine. PMID- 21026785 TI - Studies of the proteins of the tung nut A. fordii. PMID- 21026786 TI - Cell division in relation to excessive fatigue. PMID- 21026787 TI - Erythrocytes and hemostasis in hemophilia-like swine. PMID- 21026788 TI - The adjustment of the injured under the Missouri Workmen's Compensation Act. PMID- 21026789 TI - Heterotaxy; a bibliography of visceral transposition in man. PMID- 21026790 TI - Incomplete breakdown; a cathode de-ionization effect. PMID- 21026791 TI - Micro-stimulation of the human retina. PMID- 21026792 TI - Effect of acute starvation on the adrenals of the white rat. PMID- 21026793 TI - Apparatus for measuring mean cell-diameters in blood film. PMID- 21026794 TI - Substances related to vitamin A. PMID- 21026795 TI - CHROMATOGRAPHIC analysis. PMID- 21026796 TI - Thermothyrin A and B; temperature-regulating hormones of the thyroid. PMID- 21026797 TI - Influence of carbamic esters (urethanes) on experimental animal tumors. PMID- 21026798 TI - An antibiotic from Spiraea aruncus L. PMID- 21026799 TI - Pyruvic acid in the juice of onion (Allium cepa). PMID- 21026800 TI - Sweat glands. PMID- 21026801 TI - Abnormal precipitation of proteins from antitoxic horse plasma in the presence of phenolic compounds. PMID- 21026802 TI - Postulates of probability. PMID- 21026803 TI - A dropping mercury electrode of improved sensitivity. PMID- 21026804 TI - Instantaneous presentation of infra-red spectra on a cathode ray screen. PMID- 21026805 TI - Action of tyrocidin and detergents in liberating aminoacids from bacterial cells. PMID- 21026806 TI - New iron reagents for alkaline solutions. PMID- 21026807 TI - Study of the gonadotrophic activity of the hypophysis in situ. PMID- 21026808 TI - Thermostable endotoxin of rickettsiae. PMID- 21026809 TI - Golgi apparatus by phase contrast microscopy. PMID- 21026810 TI - Nature of time. PMID- 21026812 TI - Plant physiology in the U.S.S.R. PMID- 21026811 TI - NUTRITION in British Colonial territories. PMID- 21026816 TI - The metabolism and physiological effects of alcohol. PMID- 21026817 TI - Occurrence of mitotic crossing-over without meiotic crossing-over. PMID- 21026818 TI - Linkage and crossing-over between black pigmentation and susceptibility to induced fibrosarcoma in mice. PMID- 21026819 TI - Haploidy as a factor in the polymorphic differentiation of the Hymenoptera. PMID- 21026820 TI - Carcinogenic substances from pituitary glands of cattle. PMID- 21026821 TI - Nucleosis of skeletal muscle; its value as a biological test. PMID- 21026822 TI - On the fluorometric determination of nicotinamide. PMID- 21026824 TI - Pathogenesis of kernicterus. PMID- 21026823 TI - Chloride-free filter paper. PMID- 21026825 TI - The impact of the war on medicine. PMID- 21026826 TI - Anatomy and the concept of analogy. PMID- 21026828 TI - Treatment of severe erythroblastosis by simultaneous removal and replacement of the blood of the newborn infant. PMID- 21026827 TI - Synthesis of biologically active vitamin A substances. PMID- 21026829 TI - The apparent antagonism between vitamin A and carotenoids in the fowl. PMID- 21026830 TI - The effect of tocopherols in preventing gastric ulcers in rats. PMID- 21026831 TI - Identification of small amounts of organic compounds by distribution studies; use of a solid phase. PMID- 21026832 TI - The Senate and S. 1850. PMID- 21026833 TI - Japanese scientific men. PMID- 21026834 TI - The serodiagnosis of amebiasis. PMID- 21026835 TI - Histochemical localization of adenosinetriphosphatase. PMID- 21026836 TI - Anent blood relationship. PMID- 21026837 TI - Carcinogenesis and cell adaptations. PMID- 21026838 TI - The evolution of the race idea in modern Western culture during the period of the pre-Darwinian nineteenth century. PMID- 21026839 TI - The history of the malaria treatment of general paralysis. PMID- 21026840 TI - A three-year survey of electroshock therapy; report on 276 cases; comparative value of insulin-coma therapy. PMID- 21026842 TI - Disappearance of painful phantom limbs after electric shock treatment. PMID- 21026841 TI - Complications in electric shock therapy. PMID- 21026843 TI - Experiences with the pharmacologic shock therapies in the psychoses in military personnel. PMID- 21026844 TI - The physician and the Federal narcotic law. PMID- 21026846 TI - Mental accountability under military law in Canada. PMID- 21026845 TI - Mental accountability under military law. PMID- 21026847 TI - Emotional reactions of American soldiers to an unfamiliar disease. PMID- 21026848 TI - Prognosis of war neuroses without psychotherapy. PMID- 21026849 TI - Effects of heavy aerial bombardment on prisoners of war. PMID- 21026850 TI - Psychodynamics of confinement of wartime military offenders. PMID- 21026851 TI - Neurosis and group motivation. PMID- 21026852 TI - The treatment of hysterical deafness at Hoss General Hospital. PMID- 21026853 TI - Furlough psychosis. PMID- 21026854 TI - Personality studies of marihuana addicts. PMID- 21026855 TI - Psychiatric aspects of uremia. PMID- 21026856 TI - NEUROSES and psychoses. PMID- 21026857 TI - [Not Available]. PMID- 21026858 TI - [Not Available]. PMID- 21026859 TI - [Not Available]. PMID- 21026860 TI - [Not Available]. PMID- 21026861 TI - [Not Available]. PMID- 21026862 TI - [Not Available]. PMID- 21026863 TI - [Not Available]. PMID- 21026864 TI - [Not Available]. PMID- 21026865 TI - [Not Available]. PMID- 21026866 TI - [Not Available]. PMID- 21026867 TI - [Not Available]. PMID- 21026868 TI - [Not Available]. PMID- 21026869 TI - [Not Available]. PMID- 21026870 TI - [Not Available]. PMID- 21026871 TI - [Not Available]. PMID- 21026872 TI - [Not Available]. PMID- 21026873 TI - [Not Available]. PMID- 21026874 TI - [Not Available]. PMID- 21026875 TI - [Not Available]. PMID- 21026876 TI - [Not Available]. PMID- 21026877 TI - [Not Available]. PMID- 21026878 TI - [Not Available]. PMID- 21026879 TI - [Not Available]. PMID- 21026880 TI - [Not Available]. PMID- 21026881 TI - [Not Available]. PMID- 21026882 TI - [Not Available]. PMID- 21026883 TI - [Not Available]. PMID- 21026884 TI - [Not Available]. PMID- 21026885 TI - [Not Available]. PMID- 21026886 TI - [Not Available]. PMID- 21026887 TI - [Not Available]. PMID- 21026889 TI - [Not Available]. PMID- 21026890 TI - [Not Available]. PMID- 21026888 TI - [Not Available]. PMID- 21026891 TI - [Not Available]. PMID- 21026892 TI - [Not Available]. PMID- 21026893 TI - [Not Available]. PMID- 21026894 TI - [Not Available]. PMID- 21026895 TI - [Not Available]. PMID- 21026896 TI - [Not Available]. PMID- 21026897 TI - Changes in sensory adaptation time and after-sensation with lesions of parietal lobe. PMID- 21026898 TI - Significance of corneal and pharyngeal reflexes in neurology and psychiatry. PMID- 21026899 TI - Hereditary scleroses. PMID- 21026900 TI - Narcolepsy; theory of pathogenesis of the narcolepsycataplexy syndrome. PMID- 21026901 TI - Disturbances in sleep mechanism; a clinicopathologic study; anatomic and neurophysiologic considerations. PMID- 21026902 TI - Extensive erosion of the base of the skull from a leptomeningeal cyst; report of a case. PMID- 21026903 TI - Paroxysmal autonomic crises in the postencephalitic state; report of a case. PMID- 21026904 TI - Electroencephalographic changes associated with psychopathic personalities. PMID- 21026905 TI - Natural history of sciatic neuritis. PMID- 21026906 TI - Acute alterable states in multiple sclerosis. PMID- 21026907 TI - Reactions following electric shock treatment. PMID- 21026908 TI - Histopathologic effects of anoxia on the central nervous system. PMID- 21026909 TI - Histologic changes in the brain resulting from various anoxic conditions. PMID- 21026911 TI - Penicillin treatment of neurosyphilis; a preliminary report on seventy patients followed from four to twelve months. PMID- 21026910 TI - Pathologic changes associated with injury to nerve induced by cold. PMID- 21026913 TI - Behavior problems in an Army Service Forces training center. PMID- 21026912 TI - Spain as the cradle of psychiatry. PMID- 21026914 TI - Cross section perspective of current psychiatric cases at the juvenile court. PMID- 21026915 TI - Group psychotherapy in a convalescent hospital; organization and method. PMID- 21026917 TI - The thematic apperception test. PMID- 21026916 TI - Care and treatment of the mentally ill in Illinois. PMID- 21026918 TI - Prevention of postconvulsive hyperexcitability in electro-shock therapy. PMID- 21026919 TI - Toxoplasmic encephalitis. PMID- 21026920 TI - The brain in a case of human cyclopia. PMID- 21026921 TI - Attitudes, conscious and unconscious. PMID- 21026922 TI - Bilaterally synchronous paroxysmal slow activity in the electroencephalograms of non-epileptics. PMID- 21026923 TI - Brother Klaus, with a translation of Jung's commentary. PMID- 21026924 TI - The clinical status of unmixed types of primary lateral sclerosis after 24 years of observation (subacute degeneration). PMID- 21026925 TI - Group psychotherapy in private psychiatric practice; a prospectus. PMID- 21026926 TI - Intravenous histamine treatment of migraine. PMID- 21026927 TI - Psychiatry in a general hospital. PMID- 21026929 TI - Phylectic manifestations and reversions. PMID- 21026928 TI - Patient with suprasellar calcified lesion of unusual size. PMID- 21026930 TI - Sensory suppression phenomena. PMID- 21026931 TI - Brain tumor: its contribution to neurology in the remote and recent past. PMID- 21026932 TI - Acute myelitis; a clinical-pathologic study. PMID- 21026933 TI - Schizencephalies; a study of the congenital clefts in the cerebral mantle; clefts with fused lips. PMID- 21026934 TI - Central nervous system resistance; the effects of temporary arrest of cerebral circulation for periods of two to ten minutes. PMID- 21026935 TI - Fibrosarcoma of the sphenoid bone, producing the syndrome of the lateral wall of the cavernous sinus; a case report. PMID- 21026936 TI - The cerebral cortex in the very old human brain. PMID- 21026937 TI - Diastematomyelia; report of a clinical case. PMID- 21026938 TI - A note on a mechanism of arterial rupture in cerebral arteriosclerosis. PMID- 21026939 TI - Instructions for using the cutaneous resistance recorder, or dermometer, on peripheral nerve injuries, sympathectomies and paravertebral blocks. PMID- 21026940 TI - Electrospinogram (ESG); spinal cord action potentials recorded from a paraplegic patient. PMID- 21026941 TI - Cranioplasty with acrylic plates. PMID- 21026942 TI - Concussion of the spinal cord in battle casualties. PMID- 21026943 TI - Sensations of electric shock on flexion of the neck as a sign of head injury. PMID- 21026944 TI - Ventricular electroencephalography; a description of the technique. PMID- 21026945 TI - Suture of the posterior tibial nerve below the knee, with a follow-up study of the clinical results. PMID- 21026946 TI - Reversibility of cerebral ventricular dilatation. PMID- 21026947 TI - Penetrating craniocerebral injuries; evaluation of the late results in a group of 200 consecutive penetrating cranial war wounds. PMID- 21026948 TI - Coarctation of the walls of the lateral angles of the lateral cerebral ventricles. PMID- 21026949 TI - Bulb irrigator for use in neurological surgery. PMID- 21026950 TI - Arterial angioma. PMID- 21026951 TI - Nerve stimulation in paraplegic patients by means of buried induction coil; preliminary report. PMID- 21026952 TI - Paravertebral injection of procaine for pain produced by aortic aneurysm. PMID- 21026953 TI - A technique of nerve suture. PMID- 21026954 TI - Home training for mentally deficient children in New Jersey. PMID- 21026955 TI - [Not Available]. PMID- 21026956 TI - An open letter from members of the Army Nurse Corps. PMID- 21026957 TI - Nursing care of a patient on a Stryker frame. PMID- 21026958 TI - The general staff nurse considers her job and herself. PMID- 21026960 TI - When disaster strikes. PMID- 21026961 TI - Preference Record in the counseling of nurses. PMID- 21026959 TI - Facts about diapering. PMID- 21026962 TI - Tuberculosis in older persons. PMID- 21026963 TI - How Federal civil service works in relation to nurses. PMID- 21026964 TI - Referral of patients for home nursing. PMID- 21026965 TI - PROPOSED course in advanced clinical tubculosis nursing. PMID- 21026966 TI - Folk-lore and food. PMID- 21026967 TI - Maturity; a requirement for leadership. PMID- 21026969 TI - What have Canadian nurses to offer industry? PMID- 21026968 TI - Streptomycin and related phenomena. PMID- 21026970 TI - The student nurse as a health teacher. PMID- 21026971 TI - Nursing on an eye ward. PMID- 21026972 TI - Case finding in tuberculosis. PMID- 21026973 TI - [Not Available]. PMID- 21026974 TI - Comparing preventive medicine in Korea and Canada. PMID- 21026975 TI - Surgical case history: umbilical hernia. PMID- 21026976 TI - Bedside care in the home. PMID- 21026977 TI - The mock accident in first-aid training; swallowing of corrosive poison. PMID- 21026978 TI - Predecessors of penicillin; maggots and rust for wounds. PMID- 21026979 TI - Broad principles of the treatment of burns. PMID- 21026981 TI - Certain medical diseases in pregnancy. PMID- 21026980 TI - Post-encephalitic parkinsonism. PMID- 21026982 TI - Job analysis and the nursing profession. PMID- 21026983 TI - The mock accident in first-aid training; hand and arm laceration, turret lathe work. PMID- 21026984 TI - Uterine prolapse; its causes and treatment. PMID- 21026985 TI - Job analysis and the nursing profession; selection of nurses. PMID- 21026986 TI - Hypertherm treatment for gonorrhoea. PMID- 21026987 TI - Acute nephritis. PMID- 21026988 TI - Behaviour of cervix during labour. PMID- 21026989 TI - Tuberculous ulcer of ileum. PMID- 21026990 TI - Simple eye treatments. PMID- 21026992 TI - Scrub typhus. PMID- 21026991 TI - Simple ear, nose and throat out-patients' treatments. PMID- 21026993 TI - Carcinoma of the urinary tract. PMID- 21026994 TI - PENICILLIN at Oxford. PMID- 21026995 TI - The use of chemotherapy and penicillin in acute infections, with particular reference to the ear. PMID- 21026996 TI - Psoriasis. PMID- 21026997 TI - Housing; its effects on the nation's health. PMID- 21026998 TI - [Not Available]. PMID- 21026999 TI - Bowen's disease of the conjunctiva. PMID- 21027000 TI - Preglaucoma. PMID- 21027001 TI - Snydrome of uveitis, meningo-encephalitis, alopecia, poliosis, and dysacousia. PMID- 21027002 TI - Bilateral uveitis with retinal detachment poliosis, alopecia, and dysacousia. PMID- 21027003 TI - The influence of vehicles and form of penicillin and sulfonamides on mitosis and healing of corneal burns. PMID- 21027004 TI - Overseas ophthalmology. PMID- 21027005 TI - The removal of adjacent nevi of the eyelids. PMID- 21027006 TI - The relationship of rubella in the mother to congenital cataracts in the child. PMID- 21027007 TI - Hysterical amblyopia; its differentiation from malingering. PMID- 21027008 TI - Accessory lacrimal gland on the cornea. PMID- 21027009 TI - Herpes zoster ophthalmicus with varied complication. PMID- 21027010 TI - A simple method for the exact measurement and placement of recession sutures. PMID- 21027011 TI - A new type of surgical peg. PMID- 21027012 TI - New injury, diplopia from old injury. PMID- 21027013 TI - Interstitial keratitis. PMID- 21027014 TI - Monocular multiple vision. PMID- 21027015 TI - Diabetic retinopathy. PMID- 21027016 TI - Eye complications in diabetes from the standpoint of the internist. PMID- 21027017 TI - Traumatic iridodialysis; its surgical correction. PMID- 21027018 TI - Reevaluation of the Herbert flap operation for glaucoma. PMID- 21027019 TI - Intravitreal penetration of penicillin and penicillin therapy of infections of the vitreous. PMID- 21027020 TI - Penicillin in ophthalmology (practical viewpoints). PMID- 21027021 TI - Choline in serpiginous ulcers of the cornea. PMID- 21027022 TI - A national program for training in ophthalmology. PMID- 21027023 TI - Tridione and the eye. PMID- 21027024 TI - Dispensing with bifocals. PMID- 21027025 TI - HARVARD-AO fellowship investigates effects of ultra violet rays upon the eyes. PMID- 21027026 TI - Paralysis of ocular elevation with and without ptosis. PMID- 21027027 TI - Paralysis of convergence with bilateral ring scotoma following injury to occipital region. PMID- 21027028 TI - Keratoconjunctivitis sicca and buccoglossopharyngitis sicca with enlargement of parotid glands; report of two cases of Sjogren's syndrome, with pathologic study of a lacrimal gland and the parotid glands in one case. PMID- 21027029 TI - Vascular disease associated with angioid streaks of the retina and pseudoxanthoma elasticum. PMID- 21027030 TI - Tests for the detection and analysis of color blindness; the Rabkin test. PMID- 21027031 TI - Hyperpyrexia in treatment of ocular conditions due to syphilis. PMID- 21027032 TI - Partial cataract in men of military age. PMID- 21027033 TI - The cornea; permeability of the excised cornea to ions, as determined by measurements of impedance. PMID- 21027034 TI - An instrument for keratoplasty; new forceps to facilitate the preparatory suture of the transplant. PMID- 21027035 TI - Seesaw nystagmus associated with choroiditis and positive neutralization test for toxoplasma. PMID- 21027036 TI - Cylindric lenses. PMID- 21027037 TI - Senile hyaline scleral plaques. PMID- 21027038 TI - Study of visual fields with the tangent screen. PMID- 21027039 TI - Pathologic changes in the retina accompanying Tay-Sachs disease. PMID- 21027040 TI - Recession of the inferior oblique muscle. PMID- 21027041 TI - O'Connor advancement (cinch) operation. PMID- 21027042 TI - Orthoptic treatment of convergence insufficiency. PMID- 21027043 TI - Corneal section with long bevel and conjunctival flap for cataract extraction; preliminary report. PMID- 21027044 TI - Refraction by the astigmatic eye. PMID- 21027045 TI - Significance of aniseikonia in aviation. PMID- 21027046 TI - Medical treatment of acute glaucoma. PMID- 21027047 TI - Cataract associated with intraocular tumors. PMID- 21027048 TI - Syphilitic uveitis; diagnosis, Herxheimer reaction and results of various treatments, including penicillin therapy. PMID- 21027049 TI - Reticulum cell sarcoma of the conjunctiva. PMID- 21027050 TI - Aqueous fibrin fixation of corneal transplants in the rabbit. PMID- 21027051 TI - Conjunctivitis and dermatitis due to beach apple; report of thirteen cases. PMID- 21027052 TI - Alkali burns of the eye; review of the literature and summary of present knowledge. PMID- 21027053 TI - Optics in scientific crime detection. PMID- 21027054 TI - Color photomicrography. PMID- 21027055 TI - Evolution of cataract operation. PMID- 21027056 TI - Interstitial keratitis. PMID- 21027057 TI - Penicillin in ophthalmology. PMID- 21027058 TI - Penicillin in follicular conjunctivitis. PMID- 21027059 TI - A classification of photographic lens types. PMID- 21027060 TI - Theory of an efficient interference filter. PMID- 21027061 TI - The evaluation of colorimetic tristimulus values by means of a new centroid method. PMID- 21027062 TI - Photoelectric properties of metals in a finely divided state. PMID- 21027063 TI - The trigonometrical correction of microscope objectives. PMID- 21027064 TI - Modified Rayleigh scattering in a liquid. PMID- 21027065 TI - Penicillin treatment of late infection following fistulating operations. PMID- 21027066 TI - [Not Available]. PMID- 21027067 TI - [Not Available]. PMID- 21027068 TI - [Not Available]. PMID- 21027069 TI - Fallacy of prescribing bifocals indiscriminately. PMID- 21027070 TI - Fitting contact lenses by spot alteration. PMID- 21027071 TI - Allergy and its relation to disturbances of the eye. PMID- 21027073 TI - Choosing the patient for visual training. PMID- 21027072 TI - Retrobulbar neuritis; a case history. PMID- 21027074 TI - Spasm of accommodation in myopia. PMID- 21027075 TI - Thyrotoxic and thyrotropic exophthalmos from the ophthalmologist's viewpoint. PMID- 21027076 TI - Galvanic test of the labyrinth. PMID- 21027077 TI - Corresponding and oblique movements in retinoscopy. PMID- 21027078 TI - Benzyl cinnamate in treatment of Meniere's syndrome and tinnitus aurum; a clinical report. PMID- 21027079 TI - Plasma cell granuloma. PMID- 21027080 TI - Pemphigus mucosae. PMID- 21027081 TI - The relation of the nose to sexual activity. PMID- 21027082 TI - Cyclodialysis in combined glaucoma and cataract surgery. PMID- 21027083 TI - The evaluation of spontaneous vertical nystagmus. PMID- 21027084 TI - Digest of study of speech correction in cities of 100,000 and over. PMID- 21027086 TI - An analysis of professional eye care and industrial efficiency. PMID- 21027085 TI - Blepharoptosis, congenital and acquired. PMID- 21027087 TI - Vision testing in an automotive accessories industry. PMID- 21027088 TI - Visual skills analyzed brings results; a plant experience. PMID- 21027089 TI - The pathology of scrub typhus. PMID- 21027090 TI - Observations on glucose tolerance tests with special reference to glucose tolerance in patients with jaundice. PMID- 21027091 TI - Acute systemic lupus erythematosis. PMID- 21027092 TI - Masked renal insufficiency. PMID- 21027093 TI - Normal values for certain tests of liver function in healthy soldiers. PMID- 21027094 TI - The effects of the transfusion of group O blood of high iso-agglutinin titer into recipients of other blood groups. PMID- 21027095 TI - Experimental jugular phlebitis. PMID- 21027096 TI - Extramedullary plasma cell tumor of the stomach; a case report. PMID- 21027097 TI - Cancerous cyst of the tail of the pancreas simulating carcinosarcoma. PMID- 21027098 TI - The specific gravity of cerebrospinal fluid; a review of methods and the application of a newer micromethod in spinal anesthesia. PMID- 21027099 TI - An accurate and rapid method for the determination of proteins in small amounts of blood serum and plasma. PMID- 21027100 TI - A rapid method of staining frozen sections of tissue for immediate diagnosis. PMID- 21027101 TI - A new staining method for histologic sections; preliminary report. PMID- 21027102 TI - Celloidin-gum mastic film on microtome knife edge to facilitate sectioning of paraffin-embedded brain tissue. PMID- 21027103 TI - Direct application of potassium bichromate and mercuric chloride to staining solutions requiring these agents as mordants in fixation for embedding. PMID- 21027104 TI - Stain for rickettsiae and rickettsia-like organisms in tissues. PMID- 21027105 TI - Paraffin sections to demonstrate cellular elements in body fluids. PMID- 21027106 TI - Rush section. PMID- 21027107 TI - Four useful suggestions to tissue technicians. PMID- 21027109 TI - Celloidin processing of eyeball to preserve contiguity of elements. PMID- 21027108 TI - Frozen sections. PMID- 21027110 TI - Experimental production of urate calculi in the urinary tract of white rats. PMID- 21027111 TI - The enzymes of healing wounds; the effect of different degrees of vitamin C deficiency on the phosphatase activity in experimental wounds in the guinea-pig. PMID- 21027112 TI - Differential centrifugalization of intranuclear particles in the bean root and in animal tissues. PMID- 21027113 TI - Grey lung virus, an agent pathogenic for mice and other rodents. PMID- 21027114 TI - A specific blood group O substance. PMID- 21027115 TI - Fracture metabolism at different levels of protein intake. PMID- 21027116 TI - Production of antibiotics by fungi. PMID- 21027117 TI - The influence of temperature on the adaptation of tetrathionase in washed suspensions of Bact. paratyphosum B. PMID- 21027118 TI - The biosynthesis of tryptophan by Bact. typhosum. PMID- 21027119 TI - Allergenic interrelationship of epidermis, blood serum, and skeletal muscle. PMID- 21027121 TI - Clinical results with benadryl. PMID- 21027120 TI - Histamine antagonists; the effect of oral and local use of beta dimethylamincethyl benzhydryl ether hydrochloride on the whealing due to histamine, antigen-antibody reactions, and other whealing mechanisms; therapeutic results in allergic manifestations. PMID- 21027122 TI - beta-dimethylaminoethyl benzhydryl ether hydrochloride (benadryl); its use in allergic diseases. PMID- 21027123 TI - The symptomatic treatment of bronchial asthma and hay fever with beta dimethylaminoethyl benzhydryl ether hydrochloride. PMID- 21027124 TI - Antihistaminic substances with special reference to pyribenzamine. PMID- 21027125 TI - Penicillin therapy in chronic bronchial asthma. PMID- 21027127 TI - [Not Available]. PMID- 21027126 TI - The treatment of asthma with rectal suppositories of aminophylline and sodium pentobarbital. PMID- 21027128 TI - [Not Available]. PMID- 21027129 TI - [Not Available]. PMID- 21027130 TI - [Not Available]. PMID- 21027131 TI - [Not Available]. PMID- 21027132 TI - [Not Available]. PMID- 21027133 TI - [Not Available]. PMID- 21027134 TI - [Not Available]. PMID- 21027135 TI - Megaloblastic anemia in infancy; a common syndrome responding specifically to folic acid therapy. PMID- 21027136 TI - Effect of war-imposed dietary limitations on growth of Paris school children. PMID- 21027137 TI - Effect of growth and development on abnormal labial frenum. PMID- 21027138 TI - Pernicious anemia in childhood. PMID- 21027139 TI - Erythrophagocytosis in acute hemolytic anemia of the newborn; a report of three cases. PMID- 21027140 TI - Typhoid empyema; report of a case with recovery. PMID- 21027141 TI - Coronary occlusive disease in infants and in children. PMID- 21027142 TI - [Not Available]. PMID- 21027143 TI - On malignant new growth in Filipino children. PMID- 21027144 TI - On amyotonia congenita (Oppenheim's disease). PMID- 21027145 TI - Sinus bradycardia in acute rheumatic fever; report of two cases. PMID- 21027146 TI - Borderline cases of pyloric stenosis. PMID- 21027147 TI - The reticulo-endothelial system. PMID- 21027148 TI - The constitutional treatment of pertussis. PMID- 21027149 TI - Gangrena cutanea multiple. PMID- 21027150 TI - [Not Available]. PMID- 21027151 TI - [Not Available]. PMID- 21027152 TI - [Not Available]. PMID- 21027153 TI - [Not Available]. PMID- 21027154 TI - [Not Available]. PMID- 21027155 TI - [Not Available]. PMID- 21027156 TI - Mass projecting from vagina. [Sarcoma botryoides]. PMID- 21027157 TI - Swelling of the neck. [Hodgkin's disease]. PMID- 21027158 TI - Abdominal pain; vomiting; fever. [Hydronephrosis]. PMID- 21027159 TI - Congenital abnormalities. [Bladder duplication]. PMID- 21027160 TI - Meningococcemia. PMID- 21027161 TI - The problem of the child born of a diabetic mother. PMID- 21027162 TI - Spontaneous pneumothorax. PMID- 21027163 TI - Congenital lung atelectasis. PMID- 21027164 TI - The present position of deafness. PMID- 21027165 TI - Pediatrics in the U.S.S.R. PMID- 21027167 TI - TREATMENT of communicable diseases. PMID- 21027166 TI - Treatment of infective diarrhoea of infants. PMID- 21027169 TI - Health protection; 1946 model. PMID- 21027168 TI - Penicillin in congenital syphilis. PMID- 21027170 TI - The community and the schools. PMID- 21027171 TI - SCREENING, eye examinations, and follow-up. PMID- 21027172 TI - Fitting the young hard-of-hearing child for school through the auditory approach. PMID- 21027173 TI - The school nurse and her relationship to the school patrons. PMID- 21027174 TI - The effect of fluorescent light on vision. PMID- 21027175 TI - [Not Available]. PMID- 21027176 TI - [Not Available]. PMID- 21027177 TI - [Not Available]. PMID- 21027179 TI - [Not Available]. PMID- 21027178 TI - [Not Available]. PMID- 21027180 TI - [Not Available]. PMID- 21027181 TI - Mental health of teachers. PMID- 21027182 TI - BRITISH National Health Service Bill. PMID- 21027183 TI - The determination of barbiturates in toxicological and clinical investigations. PMID- 21027184 TI - Sir Kenelm Digby and the powder of sympathy. PMID- 21027185 TI - FOLIC acid in macrocytic anemia. PMID- 21027186 TI - DIHYDROERGOTAMINE and histamine for migraine. PMID- 21027187 TI - Hemorrhage control. PMID- 21027188 TI - RESISTANCE to antibiotics. PMID- 21027189 TI - DEVELOPMENT of the antimalarial paludrine. PMID- 21027190 TI - Allergy; a sketch of its past and future. PMID- 21027192 TI - STUDY of surface-active agents as bases. PMID- 21027191 TI - Acetarsone, carbarsone and iodochlorohydroxyquinoline. PMID- 21027193 TI - Progress in antimalaria therapy. PMID- 21027194 TI - The chemotherapeutic properties of 5-nitro-2-furaldehyde semicarbazone (furacin). PMID- 21027195 TI - A biological assay method for determing 2,2 bis (p-chlorophenyl)-1,1,1 trichloroethane (DDT). PMID- 21027196 TI - 2,2-bis (p-chlorophenyl)-1,1,1-trichloroethane (DDT) in the tissues, body fluids and excreta of the rabbit following oral administration. PMID- 21027197 TI - Toxicity of certain halogen substituted aliphatic acids for white mice. PMID- 21027198 TI - The biological assay of epinephrine. PMID- 21027199 TI - The effect of azochloramide on sulfonamide activity. PMID- 21027200 TI - Vitamin A concentrates, marine oil fractions, and vitamin K in the treatment of experimental renal hypertension. PMID- 21027201 TI - The inactivation of pitocin and pitressin by human pregnancy blood. PMID- 21027202 TI - MILK through the ages. PMID- 21027203 TI - ATROPHIC vaginitis. PMID- 21027204 TI - Ageing of the skin. PMID- 21027205 TI - FROSTBITE. PMID- 21027206 TI - SPRING cough. PMID- 21027207 TI - ARTHRALGIA. PMID- 21027209 TI - Pharmaceutical research and the public. PMID- 21027208 TI - Note on the stability of adrenaline solutions. PMID- 21027210 TI - PHARMACY in the services. PMID- 21027211 TI - The mode of action of some antibiotics. PMID- 21027212 TI - The mode of action of some antibiotics; penicillin. PMID- 21027213 TI - Ointment therapy. PMID- 21027214 TI - Small scale ampoule work. PMID- 21027215 TI - The present status of varicose vein sclerosing agents. PMID- 21027216 TI - Vaccines and sera. PMID- 21027217 TI - [Not Available]. PMID- 21027219 TI - DRUG therapy and diagnosis of neurologic disorders. PMID- 21027218 TI - [Not Available]. PMID- 21027220 TI - INFERTILITY: endocrine therapy. PMID- 21027221 TI - PRIMARY hepatic carcinoma. PMID- 21027222 TI - FEMALE sex hormones. PMID- 21027223 TI - CERTAIN controversial aspects of parenteral penicillin therapy. PMID- 21027224 TI - IMMUNIZATION against epidemic influenza. PMID- 21027225 TI - INFLUENZA virus vaccine; types A and B. PMID- 21027226 TI - TRIDIONE: new hope in epilepsy. PMID- 21027227 TI - RH complex; newer studies improve prognosis. PMID- 21027228 TI - Early recognition of cancer; an important factor in lessening mortality. PMID- 21027229 TI - LEUKEMIA. PMID- 21027230 TI - The renal action of posterior pituitary extract and its fractions as analysed by clearance experiments on rats. PMID- 21027231 TI - Factors influencing deposition of glycogen in adipose tissue of the rat. PMID- 21027232 TI - Temperature and blood flow in the human forearm. PMID- 21027233 TI - The effect of magnesium deficiency on neuro-muscular transmission in the shore crab, Carcinus maenas. PMID- 21027234 TI - The normal visual (rod) field of the dark-adapted eye. PMID- 21027235 TI - The stimulating action of acetylcholine on the heart. PMID- 21027236 TI - Normal variations in blood haemoglobin concentration. PMID- 21027237 TI - The effects of adrenaline on blood haemoglobin concentration. PMID- 21027238 TI - Properties and distribution of the enzyme system which synthesizes acetylcholine in nervous tissue. PMID- 21027239 TI - Circulatory changes during fainting and coma caused by oxygen lack. PMID- 21027240 TI - The effect of ethyl alcohol and some other diuretics on chloride excretion in man. PMID- 21027241 TI - The osmotic pressure of human foetal and maternal sera. PMID- 21027242 TI - Human centrifuge and studies of black-out. PMID- 21027243 TI - Presso-receptors of the carotid sinus and respiration. PMID- 21027244 TI - The production of an adrenaline-like substance by the heart. PMID- 21027245 TI - Effect of magnesium ions on the enzymic formation of acetylcholine. PMID- 21027246 TI - Further observations on the causes of a diuresis during hydropenia. PMID- 21027247 TI - The psychology of togetherness. PMID- 21027248 TI - The solving of problem-situations by the preschool child. PMID- 21027249 TI - The adaptation of the preschool child to standard basal metabolism conditions. PMID- 21027250 TI - The development of directionality in drawing. PMID- 21027252 TI - The development of the sense of time in the young child. PMID- 21027251 TI - The social distance between certain racial, nationality, and skin-pigmentation groups in selected populations of American school children. PMID- 21027253 TI - Measurement of the minimum effect of environment, using two-egg twins. PMID- 21027254 TI - Age and vocational choice. PMID- 21027255 TI - Psychopathological defects in inductive reasoning. PMID- 21027256 TI - A simple electronic device for the measurement of the gross bodily activity of small animals. PMID- 21027257 TI - The multiple choice Rorschach; a critical examination of its scoring system. PMID- 21027258 TI - The efficiency of a high-speed screening procedure in detecting the neuropsychiatrically unfit at a U.S. Marine Corps recruit training depot. PMID- 21027259 TI - Prediction of response to brief psychotherapy. PMID- 21027260 TI - Activity level as a function of physically enforced inaction. PMID- 21027261 TI - The reliability of constant errors in psychophysical measurement. PMID- 21027262 TI - An aid in patient education; a tuberculosis questionnaire. PMID- 21027263 TI - Contexts of aggression; play constructions of head injuries and psychoneurotics. PMID- 21027264 TI - Group differences in fantasies; head injuries, psychoneurotics, and brain diseases. PMID- 21027265 TI - What's what about shock therapy. PMID- 21027266 TI - National planning for psychiatric education. PMID- 21027267 TI - A permanent medical survey. PMID- 21027268 TI - Reconditioning; some psychological implications. PMID- 21027269 TI - Some salient dynamic factors of the passive personality reaction type. PMID- 21027271 TI - The foster child and separation. PMID- 21027270 TI - Mental illness and family routines. PMID- 21027272 TI - The function of a psychologist in a psychiatric clinic. PMID- 21027273 TI - Mental hygiene and physical education. PMID- 21027274 TI - Significant symptoms in the behavior of young children; a check list for teachers. PMID- 21027275 TI - What shall we do with the mentally deficient? PMID- 21027276 TI - Pediatric aspects of the Salem witchcraft tragedy; a lesson in mental health. PMID- 21027277 TI - Language and psycholinguistics; a review. PMID- 21027278 TI - Objective measurement of clinical status in psychopathological research. PMID- 21027279 TI - A history of the Department of Psychology at the University of Chicago. PMID- 21027280 TI - New statistical criteria for learning and problem solution in experiments involving repeated trials. PMID- 21027281 TI - A supplementary test based on free associations to Rorschach responses. PMID- 21027282 TI - The Rorschach test in the evaluation of military personnel. PMID- 21027283 TI - The use of the Rorschach in a groupwork agency. PMID- 21027284 TI - ACUTE respiratory disease among new recruits. PMID- 21027285 TI - Pasteurization of liquid egg products; destruction of Salmonella in liquid whole egg. PMID- 21027286 TI - Need for a public health program in rheumatic fever and rheumatic heart disease. PMID- 21027287 TI - Improvement of the nasopharyngeal swab method of diagnosis in pertussis by the use of penicillin. PMID- 21027288 TI - Post-war training problems in public health. PMID- 21027289 TI - Results from the current mortality sample. PMID- 21027290 TI - A group of paracolon organisms having apparent pathogenicity. PMID- 21027291 TI - Implication of Proteus mirabilis in an outbreak of gastroenteritis. PMID- 21027292 TI - Public support for multiple county health departments. PMID- 21027293 TI - Tularemia; a report on 40 cases in Alberta, Canada, 1931-1944. PMID- 21027294 TI - Wartime changes in the age distribution of females infected with syphilis. PMID- 21027295 TI - The use of 2 x n Chi square in the analysis of change in age distributions. PMID- 21027296 TI - CASE finding in the control of syphilis. PMID- 21027297 TI - MEMORANDUM presented by the Bengal Public Health Association to the Health Survey and Development Committee of the Government of India on the public administration of the Province. PMID- 21027298 TI - ABSTRACT from Survey Report on Food Famine and Nutritional Diseases in Travancore, 1943-44. PMID- 21027299 TI - OBSERVATION of Famine Inquiry Commission in their final report. PMID- 21027300 TI - BENGAL Government's post-war reconstruction plan. PMID- 21027301 TI - FORTY YEARS of births, deaths, and marriages. PMID- 21027302 TI - The diagnosis of haemolytic streptococcal infection in acute nasopharyngitis. PMID- 21027303 TI - Indian health services. PMID- 21027304 TI - Public health nursing in the control of syphilis and gonorrhoea; public health objectives in venereal disease control. PMID- 21027305 TI - A gonococcus culture outfit for specimens submitted by mail. PMID- 21027306 TI - Immunization; ways and means of controlling communicable diseases. PMID- 21027307 TI - The use of D.D.T. in the Peace River health unit. PMID- 21027308 TI - The pasteurization of milk in Quebec. PMID- 21027310 TI - CANCER campaign international in scope. PMID- 21027309 TI - Proteins essential for the human factory. PMID- 21027311 TI - A model public health school unit. PMID- 21027312 TI - Sports for the handicapped. PMID- 21027313 TI - The Canadian Physical Education Association. PMID- 21027314 TI - Fluorine versus tooth decay. PMID- 21027315 TI - Massachusetts industrial x-ray program. PMID- 21027316 TI - Rheumatic fever program in Cambridge. PMID- 21027317 TI - The preventive and therapeutic use of vitamins. PMID- 21027318 TI - Pertussis immunisation programme of the Boston Health Department. PMID- 21027319 TI - Tinea pedis (athlete's foot). PMID- 21027320 TI - Bovine tuberculosis. PMID- 21027321 TI - An outbreak of food poisoning caused by Salmonella typhi-murium, conveyed by infected gelatin. PMID- 21027323 TI - Epidemic influenza due to virus B. PMID- 21027322 TI - An outbreak of streptococcal infection in a nursery school in West Suffolk. PMID- 21027324 TI - TUBERCULOSIS record systems. PMID- 21027325 TI - The modalities of bed rest. PMID- 21027326 TI - Isolation of Mycobacterium tuberculosis from gastric contents neutralized after varying periods. PMID- 21027327 TI - How much control of tuberculosis. PMID- 21027328 TI - How does housing affect health? PMID- 21027329 TI - Comparative assays of rodenticides on wild Norway rats; toxicity. PMID- 21027330 TI - Malaria; numbers of cases reported by the State health officers in 1945 as compared with similar data for the years 1939-1944. PMID- 21027331 TI - Chlorine as a possible ovicide for Aedes aegypti eggs. PMID- 21027332 TI - Aedes tortilis (Theobald), a mosquito new to the United States. PMID- 21027333 TI - [Not Available]. PMID- 21027334 TI - [Not Available]. PMID- 21027335 TI - [Not Available]. PMID- 21027336 TI - [Not Available]. PMID- 21027338 TI - [Not Available]. PMID- 21027337 TI - [Not Available]. PMID- 21027339 TI - [Not Available]. PMID- 21027340 TI - [Not Available]. PMID- 21027341 TI - [Not Available]. PMID- 21027343 TI - [Not Available]. PMID- 21027342 TI - [Not Available]. PMID- 21027344 TI - [Not Available]. PMID- 21027345 TI - [Not Available]. PMID- 21027346 TI - [Not Available]. PMID- 21027347 TI - OUTLOOK for population growth. PMID- 21027348 TI - SLIGHT setback in health record for 1946. PMID- 21027349 TI - POSTWAR increase in suicide. PMID- 21027350 TI - FATAL accident rate highest in the West. PMID- 21027351 TI - Water waste surveys and leakage correction; with particular reference to the pitometer and its use in making such surveys. PMID- 21027352 TI - U.S. drinking water standards. PMID- 21027353 TI - Filter sand specifications. PMID- 21027354 TI - Coagulation with ferric salts; with particular reference to ferric sulphate and its use. PMID- 21027356 TI - DIRECTORY of State sanitary engineers. PMID- 21027355 TI - Equipment and tools for sewage works. PMID- 21027357 TI - On the value of planigraphy in bronchial cancer. PMID- 21027359 TI - Fibro-osteoma; a pathologico-anatomical and roentgenological study. PMID- 21027358 TI - [Not Available]. PMID- 21027360 TI - [Not Available]. PMID- 21027361 TI - The movements of the mitro-aortic ring recorded simultaneously by cineroentgenography and electrocardiography. PMID- 21027362 TI - Fabella. PMID- 21027363 TI - Urography on children after administration of the contrast substance by mouth. PMID- 21027364 TI - Roentgen changes associated with pancreatic insufficiency in early life. PMID- 21027365 TI - The roentgen diagnosis of pancreatic cyst. PMID- 21027366 TI - Congenital duodenal obstruction; report of six cases and review of the literature. PMID- 21027367 TI - Diverticulosis of the jejunum and ileum. PMID- 21027368 TI - Pellegrini-Stieda disease. PMID- 21027369 TI - Spondylolisthesis; further remarks with emphasis on radiologic aspects. PMID- 21027370 TI - Energy absorption in the trunk in the radium treatment of breast cancer by interstitial and surface applicator methods. PMID- 21027371 TI - Henoch's purpura; small intestinal changes; case report. PMID- 21027373 TI - Accessory urethral channel; case report. PMID- 21027372 TI - Dysgerminoma of the ovary with widespread metastases. PMID- 21027374 TI - A new method of making radon ointment. PMID- 21027376 TI - Pelvicephalometry. PMID- 21027375 TI - Protection measurements of lead-shielded radium. PMID- 21027377 TI - Studies in vitro on cellular physiology; the effect of x-rays on the survival of cells. PMID- 21027378 TI - CYSTIC fibrosis of the pancreas. PMID- 21027379 TI - Position of fingers and function deficiency in ulnar paralysis. PMID- 21027380 TI - [Not Available]. PMID- 21027381 TI - [Not Available]. PMID- 21027382 TI - [Not Available]. PMID- 21027383 TI - On late results of operative treatment for intervertebral disc prolapses in the lumbar region. PMID- 21027384 TI - On the deformities of the spine in multiple neurofibromatosis (von Recklinghausen). PMID- 21027385 TI - [Not Available]. PMID- 21027386 TI - On the surgical treatment of scleroderma. PMID- 21027387 TI - Indefinite pain in the right flank and its origin; a new symptom of ileitis. PMID- 21027388 TI - [Not Available]. PMID- 21027389 TI - [Not Available]. PMID- 21027390 TI - [Not Available]. PMID- 21027391 TI - Gustatory local hyperhidrosis following injuries in the parotid region. PMID- 21027392 TI - On repositioned luxation fracture of the VI cervical vertebra with transverse paralysis of the spinal marrow. PMID- 21027394 TI - On extrapleural pneumolysis in pulmonary tuberculosis. PMID- 21027393 TI - [Not Available]. PMID- 21027395 TI - On the treatment of periappendicular abscesses, particularly with regard to their x-ray therapy. PMID- 21027396 TI - [Not Available]. PMID- 21027397 TI - On clostridia infections in war wounds on the Carelian Isthmus. PMID- 21027398 TI - Processus pyramidalis in struma operations. PMID- 21027399 TI - Arthrography in sequelae to acute infectious arthritis of the hips of young children. PMID- 21027400 TI - [Not Available]. PMID- 21027401 TI - Splanchnectomy by megacolon congenitum. PMID- 21027402 TI - On the practical importance of the clinical determination of the basal metabolic rate in thyrotoxicosis. PMID- 21027404 TI - Tables for calculation of exact measurements of radiographed objects. PMID- 21027403 TI - Treatment of the congenital flat-foot. PMID- 21027405 TI - Closure of the bronchus in pneumonectomy and lobectomy. PMID- 21027406 TI - Uretero-intestinal implantation according to Coffey. PMID- 21027407 TI - Bone grafts in non-union of war fractures. PMID- 21027408 TI - Thoracic surgery in the forward areas. PMID- 21027409 TI - Anesthesia for open chest surgery. PMID- 21027410 TI - Orificial technic for proctologic surgery; excision of anal pathology in situ. PMID- 21027411 TI - Anesthesia in an evacuation hospital. PMID- 21027412 TI - Early walking after major gynecologic surgery. PMID- 21027413 TI - Lumbar sympathectomy for chronic leg ulcers. PMID- 21027414 TI - Trimalleolar fractures of the ankle joint; a conservative method of treatment. PMID- 21027415 TI - The use of oxygen and oxygen liberating substances in the treatment of anaerobic peritonitis in guinea pigs. PMID- 21027416 TI - The fetal circulation is identical with the venous circulation of the adult male and female. PMID- 21027417 TI - Five years' experience with spool cotton as a suture material; routine use in over 1,000 operations. PMID- 21027418 TI - Unusual tumors of the stomach. PMID- 21027419 TI - The carotid body. PMID- 21027420 TI - Inactivation of penicillin by tubing; preliminary report. PMID- 21027421 TI - Roentgen and clinical problems in so-called solitary metastatic tumors in the chest. PMID- 21027422 TI - Submucous hemorrhoidectomy; a modification of the Calman method. PMID- 21027424 TI - Hematoma of the rectus abdominis muscle; report of a case and analysis of 100 cases from the literature. PMID- 21027423 TI - Absence of the vagina, uterus, right kidney and ureter and ectopic (pelvic) left kidney. PMID- 21027425 TI - Adenocarcinoma of the common bile duct with resection, anastomosis of the hepatic duct to the cystic duct and cholecystogastrostomy. PMID- 21027426 TI - Convulsions during anesthesia treated with intravenous sodium pentothal. PMID- 21027427 TI - Surgical importance of carcinoid tumors of the ileum. PMID- 21027428 TI - Chronic inversion of the uterus with fibrosarcoma of the corpus. PMID- 21027429 TI - [Not Available]. PMID- 21027430 TI - [Not Available]. PMID- 21027431 TI - [Not Available]. PMID- 21027432 TI - [Not Available]. PMID- 21027433 TI - [Not Available]. PMID- 21027434 TI - [Not Available]. PMID- 21027435 TI - [Not Available]. PMID- 21027436 TI - [Not Available]. PMID- 21027437 TI - [Not Available]. PMID- 21027438 TI - [Not Available]. PMID- 21027439 TI - [Not Available]. PMID- 21027440 TI - [Not Available]. PMID- 21027441 TI - [Not Available]. PMID- 21027442 TI - [Not Available]. PMID- 21027443 TI - [Not Available]. PMID- 21027444 TI - [Not Available]. PMID- 21027445 TI - Present trends in the practice of medicine and surgery. PMID- 21027446 TI - Spinal cord concussion in war wounds. PMID- 21027447 TI - Involuntary movements following nerve injuries by high velocity projectiles. PMID- 21027448 TI - Moore-Blount internal fixation of an intertrochanteric fracture of the femur in an 89 year old woman. PMID- 21027449 TI - Clinical use of prostigmin as an ideal office procedure in determining pregnancy. PMID- 21027450 TI - Fifty years of radiology; from Roentgen to the era of atomic power. PMID- 21027451 TI - [Adenocarcinoma of the pancreas]. PMID- 21027452 TI - The radiotherapeutic test in the differential diagnosis of mediastinal pathology. PMID- 21027453 TI - [Not Available]. PMID- 21027454 TI - [Not Available]. PMID- 21027455 TI - [Not Available]. PMID- 21027456 TI - [Not Available]. PMID- 21027457 TI - [Not Available]. PMID- 21027458 TI - [Not Available]. PMID- 21027459 TI - [Not Available]. PMID- 21027460 TI - [Not Available]. PMID- 21027461 TI - [Not Available]. PMID- 21027462 TI - [The immunizing properties of the phago-resistent strains of Shigella dysenteriae]. PMID- 21027463 TI - [Some questions with regard to the work of epidemiological groups]. PMID- 21027464 TI - [Parenteral immunization against dysentery with vaccines obtained by inactivation of dysenteritic bacilli in cod-liver oil]. PMID- 21027465 TI - [On enter al immunization against dysentery]. PMID- 21027466 TI - [Concerning the vaccine treatment of chronic dysentery]. PMID- 21027467 TI - [Transplantability of the dysenteritic bacilli in atypical forms of dysentery]. PMID- 21027468 TI - [Cytological method of study of the mechanism of immunity]. PMID- 21027469 TI - [The blood picture in angina septica]. PMID- 21027470 TI - [Pathological anatomy of angina septica]. PMID- 21027471 TI - [Experimental data regarding malaria immunization with formol vaccine]. PMID- 21027472 TI - [The study of combined vaccination and viral antagonism in seasonal encephalitis]. PMID- 21027473 TI - [Reactivation of the viruses of autumn encephalitis and rabies from biologically neutral mixtures with antibodies]. PMID- 21027474 TI - [Dissociation of Park-Williams culture no. 8 and toxin-formation]. PMID- 21027475 TI - [Determination of the nitrogen of antitoxin in antidiphtheritic sera]. PMID- 21027476 TI - [The comparative evaluation of the methods of titrating sera against B. perfringens]. PMID- 21027477 TI - [Precipitation and collection of blood serum from cattle in bottles and cups]. PMID- 21027478 TI - [Contribution to bacterial anaphylaxis observed in certain animals in preparing cholera agglutinizing serum]. PMID- 21027479 TI - [Determination of agglutinizing and complement binding properties of antimeningococcic sera]. PMID- 21027480 TI - [Concerning the teaching of epidemiology in the medical and pediatric faculties of the medical institutes]. PMID- 21027481 TI - [The mechanism of acquired immunity in tick encephalitis; the role of the humoral factor in the mechanism of active immunity in tick encephalitis]. PMID- 21027482 TI - [On the methods of study of the barrier-fixating manifestations of immunity in dysentery and cholera]. PMID- 21027483 TI - [Employment of vaccines of various preparations for the treatment of children with chronic dysentery]. PMID- 21027484 TI - [Contribution to the change of permeability of erythrocytes sensitized by hemolytic amboceptors for C1-, SO4- and HOO3-ions]. PMID- 21027485 TI - [The venoms of basic species of Middle Asia snakes as antigens; the study of antitoxic properties of antidotic sera]. PMID- 21027486 TI - [Active immunization against diphtheria by purified concentrated precipitated diphtheritic anatoxin]. PMID- 21027487 TI - [Antitoxic and antibacterial immunity in diphtheria]. PMID- 21027488 TI - [Concerning the role of antitoxic and antibacterial factors in antigangrenous sera antiperfringens]. PMID- 21027489 TI - [Antiphage action of antiplague sera]. PMID- 21027490 TI - [Preparation of vaccine from typhous lice, after Pshenichnov-Raikher's method]. PMID- 21027492 TI - [The lungs of the rabbit as a pattern for cultivation of Rickettsia]. PMID- 21027491 TI - [Active immunization against European typhus exanthematicus; efficacy of Durand's typhous vaccine in epidemiological experiments on men]. PMID- 21027493 TI - [The early diagnosis of typhus exanthematicus by intravenous testing]. PMID- 21027494 TI - [Weil-Felix's reaction in healthy subjects and those infected with typhus exanthematicus, vaccinated after Krontovskaya's method]. PMID- 21027495 TI - [On the test tube method employed in Weigl's reaction for the diagnosis of typhus exanthematicus]. PMID- 21027496 TI - [On rat rickettsiasis observed at B----]. PMID- 21027497 TI - [Obliterated forms of tick typhus exanthematicus]. PMID- 21027498 TI - [The phenomenon of phagocytic avidity in patients infected with Brucella]. PMID- 21027499 TI - [Comparative titration of pneumococcic sera and determination of their persistence in vivo and in vitro]. PMID- 21027500 TI - The punctulatus complex of Anopheles (Diptera: Culicidae). PMID- 21027501 TI - A new genus and species of chigger, Chatia setosa (Trombiculidae, Acarina) from northwestern United States. PMID- 21027502 TI - Studies on reactions of rat serum to eggs of Trichosomoides crassicauda, a nematode of the urinary bladder. PMID- 21027503 TI - Are vesical calculi associated with Trichosomoides crassicauda, the common bladder nematode of rats. PMID- 21027504 TI - Preliminary notes on the crustacean vector of the mammalian lung fluke (Paragonimus) in the Philippines. PMID- 21027505 TI - Plagiorchoides potamonides (Plagiorchiidae), a new trematode found in experimental rats. PMID- 21027507 TI - The trematode genus Opecoeloides and related genera, with a description of Opecoeloides polynemi n. sp. PMID- 21027506 TI - On two Acanthocephala from the Philippines. PMID- 21027508 TI - Atricholaelaps sigmodoni, a new species of mite parasitic on the cotton rat, and notes on the genera Atricholaelaps and Ischnolaelaps (Acarina: Laelaptidae). PMID- 21027509 TI - The use of dehydrated, coagulated egg yolk in the preparation of a medium for culturing Endamoeba histolytica. PMID- 21027510 TI - Functional cytology of Entamoeba histolytica. PMID- 21027511 TI - Chemical studies on egg-white medium for the cultivation of Endamoeba histolytica. PMID- 21027512 TI - Observations on Dogielella renalis, n. sp. (Astomata, Ciliophora) from the renal organ of Physella sp. PMID- 21027513 TI - Trichuris peromysci n. sp. from Peromyscus californicus, and further notes on T. perognathi Chandler, 1945. PMID- 21027514 TI - The aerosol bomb as a method for determining the triatomic index in human habitations in Chagas' disease endemic zones. PMID- 21027515 TI - Note on the tick, Ixodes angustus Neumann. PMID- 21027516 TI - Host-parasite relationships of the root-knot nematode, Heterodera marioni; some effects of the host on the parasite. PMID- 21027517 TI - Temperature effects on the expression of the yellows virus in sour cherries. PMID- 21027518 TI - Mosaics of winter oats induced by soil-borne viruses. PMID- 21027519 TI - Infection studies with Actinomyces scabies. PMID- 21027520 TI - An enzyme in the animal organism capable of hydrolyzing diisopropyl fluorophosphate. PMID- 21027521 TI - Effects of a single massive dose of vitamin D2 on young dogs. PMID- 21027522 TI - A study of the composition of cardiolipin. PMID- 21027523 TI - Effect of adrenal cortex extract on the hexokinase reaction. PMID- 21027524 TI - Synthesis of cholesterol in liver slices. PMID- 21027525 TI - Glutamic acid decarboxylase of higher plants. PMID- 21027526 TI - Changes in the serum proteins and carbohydrate in tuberculosis and methods of analysis. PMID- 21027527 TI - Effect of tryptophane on urinary excretion of nicotinic acid in rats. PMID- 21027528 TI - Estimation of vitamin A in fish liver oils by activated glycerol dichlorohydrin. PMID- 21027529 TI - Enzymatic action of cerebrospinal fluids following concussion. PMID- 21027530 TI - Effect of insulin level upon lipogenesis. PMID- 21027531 TI - A study of double hearts produced experimentally in embryos of Amblystoma punctatum. PMID- 21027532 TI - The nervous system and regeneration of the forelimb of adult Triturus; the influence of number of nerve fibers, including a quantitative study of limb innervation. PMID- 21027533 TI - The effect of local applications of colchicine on leghorn and polydactylous chick embryos. PMID- 21027534 TI - Production of strophosomy in the chick embryo by local applications of colchicine. PMID- 21027535 TI - Experiments on the formed inclusions of the amphibian egg; the effect of pH and electrolytes on yolk and lipochondria. PMID- 21027536 TI - Studies on flagellates from domesticated birds; the behavior of Trichomonas gallinarum in culture. PMID- 21027537 TI - A serologic study of conjugation in Paramecium bursaria. PMID- 21027538 TI - Regulation in the chick allantois. PMID- 21027539 TI - The fluorescence spectra of pterins and their possible use in the elucidation of the antipernicious anaemia factor. PMID- 21027540 TI - Preparation of a fluorescent substance from the eye of the dogfish, Squalus acanthias. PMID- 21027541 TI - Tetryl dermatitis; ultra-violet irradiation of tetryl (2:4:6-trinitrophenyl methyl-nitramine). PMID- 21027543 TI - Ionophoresis in silica jelly; a method for the separation of amino-acids and peptides. PMID- 21027546 TI - Metabolism of steroids; ketonic derivatives of cholic acid from cow's bile. PMID- 21027547 TI - Experiments on the chemotherapy of cancer; the effect of aromatic bases. PMID- 21027548 TI - The nature of the cation exchanges during yeast fermentation, with formation of 0 degrees 02 N-H ion. PMID- 21027550 TI - The microbiological degradation of steroids; oxidation of hydroxy-steroids to keto-derivatives by Proactinomyces spp. PMID- 21027549 TI - The metabolism and functioning of vitamin-like compounds; ammonia formation from glutamine by haemolytic streptococci; its reciprocal connexion with glycolysis. PMID- 21027558 TI - Studies on suramin (antrypol: Bayer 205); the combination of the drug with the plasma and other proteins. PMID- 21027559 TI - Chemistry of tissues; polysaccharides showing blood group A-specificity and the nature of the constituent units of the stable carbohydrate residue of the A substance from pepsin. PMID- 21027560 TI - Chemistry of tissues; blood group substances from human gastric contents. PMID- 21027561 TI - The fate of certain organic acids and amides in the rabbit; benzoic and phenylacetic acids and their amides. PMID- 21027563 TI - The toxic effects of oxygen on brain metabolism and on tissue enzymes; brain metabolism. PMID- 21027564 TI - The toxic effects of oxygen on brain metabolism and on tissue enzymes; tissue enzymes. PMID- 21027565 TI - The pharmacology of paludrine and some other new antimalarials. PMID- 21027566 TI - A rapid method for the estimation of paludrine in urine. PMID- 21027567 TI - Excretion products of mepacrine: a spectrophotometric study. PMID- 21027568 TI - Further studies on the antibacterial action of substituted aminophenols. PMID- 21027569 TI - Inhibition of urease by Cu in the presence of ascorbic acid and related substances. PMID- 21027570 TI - Some aspects of the physiology and pathology of the natural hexosamine and uronic acid compounds. PMID- 21027571 TI - Polyuronides. PMID- 21027572 TI - The mode of linkage of the amino sugars in their naturally occurring derivatives. PMID- 21027573 TI - Mucoitin sulphuric acid, chondroitin sulphuric acid, hyaluronic acid and heparin. PMID- 21027574 TI - Glycoproteins. PMID- 21027575 TI - Blood group substances. PMID- 21027576 TI - Enzymic degradation of polysaccharides containing amino sugars and uronic acids. PMID- 21027577 TI - Metabolic products containing uronic acids. PMID- 21027578 TI - [Not Available]. PMID- 21027579 TI - [Not Available]. PMID- 21027580 TI - [Not Available]. PMID- 21027581 TI - [Not Available]. PMID- 21027582 TI - [Not Available]. PMID- 21027583 TI - [Not Available]. PMID- 21027584 TI - [Not Available]. PMID- 21027585 TI - [Not Available]. PMID- 21027586 TI - [Not Available]. PMID- 21027587 TI - [Not Available]. PMID- 21027588 TI - [Not Available]. PMID- 21027589 TI - [Not Available]. PMID- 21027590 TI - [Not Available]. PMID- 21027591 TI - [Not Available]. PMID- 21027592 TI - [Not Available]. PMID- 21027594 TI - [Not Available]. PMID- 21027593 TI - [Not Available]. PMID- 21027595 TI - [Not Available]. PMID- 21027596 TI - [Not Available]. PMID- 21027598 TI - [Not Available]. PMID- 21027597 TI - [Not Available]. PMID- 21027599 TI - [Not Available]. PMID- 21027600 TI - [Not Available]. PMID- 21027601 TI - [Not Available]. PMID- 21027602 TI - [Not Available]. PMID- 21027603 TI - [Not Available]. PMID- 21027604 TI - [Not Available]. PMID- 21027605 TI - [Not Available]. PMID- 21027606 TI - [Not Available]. PMID- 21027607 TI - [Not Available]. PMID- 21027608 TI - A brief history of the Southwestern Society of Orthodontists. PMID- 21027609 TI - Orthodontic training; paradox. PMID- 21027610 TI - Preventive orthodontics. PMID- 21027611 TI - The ease with which acrylic retainers may be processed in your own office. PMID- 21027612 TI - Another case of distoclusion. PMID- 21027613 TI - Coordinating the predetermined pattern and tooth positioner with conventional treatment. PMID- 21027615 TI - Ankylosis of the mandibular joint. PMID- 21027614 TI - Indirect-direct band and appliance technique. PMID- 21027616 TI - Heredity and cyst formation. PMID- 21027617 TI - Comminuted fracture of mandible. PMID- 21027618 TI - Compound fracture of mandible with displacement of the posterior fragment. PMID- 21027619 TI - Compound fracture of the right mandible and subcondylar fracture on the left. PMID- 21027620 TI - Submaxillary abscess due to acute pericoronitis treated by aspiration and instillation of penicillin. PMID- 21027621 TI - Osteomyelitis of the mandible. PMID- 21027622 TI - Ranula. PMID- 21027623 TI - Dentigerous cyst of maxilla formed from a mesiodens. PMID- 21027624 TI - Odontogenic cyst of mandible. PMID- 21027625 TI - Myxoma of mandible. PMID- 21027626 TI - Adamantoblastoma of the mandible. PMID- 21027627 TI - Carcinoma of the maxilla. PMID- 21027628 TI - Gingivectomy; indications, contraindications, and method. PMID- 21027629 TI - [Not Available]. PMID- 21027630 TI - [Not Available]. PMID- 21027631 TI - [Not Available]. PMID- 21027632 TI - [Not Available]. PMID- 21027633 TI - The Teviot Report; dental mechanics. PMID- 21027634 TI - Experiences of a field dental laboratory in the B.L.A. PMID- 21027635 TI - Deglutition and the teeth. PMID- 21027636 TI - Cervico-facial orthopaedia. PMID- 21027637 TI - The report on facial growth in children. PMID- 21027638 TI - [Not Available]. PMID- 21027639 TI - [Not Available]. PMID- 21027640 TI - [Not Available]. PMID- 21027641 TI - [Not Available]. PMID- 21027642 TI - [Not Available]. PMID- 21027643 TI - Dental anaesthesia. PMID- 21027644 TI - Enamel solubilities. PMID- 21027645 TI - Training in oral surgery. PMID- 21027646 TI - Treatment of lupus vulgaris with calciferol. PMID- 21027647 TI - Dermatomyositis and malignant tumour. PMID- 21027648 TI - Scabies norvegica in a native of East Africa. PMID- 21027649 TI - [Not Available]. PMID- 21027650 TI - [Not Available]. PMID- 21027651 TI - [Not Available]. PMID- 21027652 TI - [Not Available]. PMID- 21027653 TI - [Not Available]. PMID- 21027655 TI - [Not Available]. PMID- 21027654 TI - [Not Available]. PMID- 21027656 TI - [Not Available]. PMID- 21027657 TI - [Not Available]. PMID- 21027659 TI - [Not Available]. PMID- 21027658 TI - [Not Available]. PMID- 21027660 TI - Chronic venous congestion of the liver and diabetes mellitus. PMID- 21027661 TI - Gerontology. PMID- 21027662 TI - Logarithmic increase in mortality as a manifestation of aging. PMID- 21027663 TI - The relation between age of stem tissue and the capacity to form roots. PMID- 21027664 TI - Observations on aging in nutritionally deficient persons. PMID- 21027665 TI - Prolongation of life with prevention of leukemia by thymectomy in mice. PMID- 21027666 TI - The Hodson Community Center; an experiment in preservation of personality. PMID- 21027667 TI - Budgeting for social security. PMID- 21027668 TI - Attitudes toward aging and the aged; primitive societies. PMID- 21027669 TI - Involution of tissues in fetal life; a review. PMID- 21027671 TI - [Control of malignant tumors of the female reproductive organs]. PMID- 21027670 TI - Shakespeare's attitude towards old age. PMID- 21027672 TI - [Precancerous state of the uterus and cervix]. PMID- 21027673 TI - [The surgical treatment of cancer of the uterus and ovaries]. PMID- 21027675 TI - [The clinical symptomatology and diagnosis of primary cancer of the uterus]. PMID- 21027674 TI - [Cancer of the cervix with reference to conjunctival tissue]. PMID- 21027676 TI - [The surgical treatment of cancer of the cervix]. PMID- 21027677 TI - [The architectonics of the vessels in cancer of the cervix]. PMID- 21027678 TI - [Contrast roentgendiagnosis of tumors of the female reproductive organs]. PMID- 21027679 TI - [On radium therapy of erosions and cancer of the cervix and pathological conditions of the uterus, including fibromyomas]. PMID- 21027680 TI - [On radiotherapy in cancer of the cervix]. PMID- 21027681 TI - [Not Available]. PMID- 21027682 TI - [Not Available]. PMID- 21027683 TI - [Not Available]. PMID- 21027684 TI - Medical history: some problems and opportunities. PMID- 21027686 TI - The formation of the Harvey Cushing collection. PMID- 21027685 TI - Medicine at Fort Detroit in the Colony of New France, 1701-1760. PMID- 21027687 TI - Government and science in the United States: historical backgrounds. PMID- 21027688 TI - Autobiography in medicine or the doctor in search of himself. PMID- 21027689 TI - Students of physic and astrology; a survey of astrological medicine in the age of science. PMID- 21027690 TI - Antiques of medical interest: nipple shields. PMID- 21027691 TI - Some wartime influences on health and welfare institutions in the United States. PMID- 21027692 TI - Against routine prescriptions for easy labor. PMID- 21027693 TI - Children's types. PMID- 21027694 TI - Homoeopathic remedies in influenza. PMID- 21027695 TI - Treatment of malaria without quinine. PMID- 21027696 TI - Pulsatilla and sepia and their relationship to sycosis. PMID- 21027697 TI - Rheumatoid arthritis; with case history report. PMID- 21027698 TI - The pre-natal examination. PMID- 21027699 TI - Primary atypical pneumonia. PMID- 21027700 TI - [Not Available]. PMID- 21027701 TI - [Not Available]. PMID- 21027702 TI - [Not Available]. PMID- 21027703 TI - [Not Available]. PMID- 21027704 TI - [Not Available]. PMID- 21027705 TI - [Not Available]. PMID- 21027706 TI - [Not Available]. PMID- 21027707 TI - [Not Available]. PMID- 21027708 TI - [Not Available]. PMID- 21027709 TI - [Not Available]. PMID- 21027710 TI - [Not Available]. PMID- 21027712 TI - [Not Available]. PMID- 21027711 TI - [Not Available]. PMID- 21027713 TI - [Not Available]. PMID- 21027714 TI - [Not Available]. PMID- 21027715 TI - [Not Available]. PMID- 21027716 TI - [Not Available]. PMID- 21027717 TI - [Not Available]. PMID- 21027718 TI - [Not Available]. PMID- 21027719 TI - [Not Available]. PMID- 21027720 TI - [Not Available]. PMID- 21027721 TI - [Not Available]. PMID- 21027723 TI - [Not Available]. PMID- 21027724 TI - [Not Available]. PMID- 21027722 TI - [Not Available]. PMID- 21027725 TI - [Not Available]. PMID- 21027726 TI - [Not Available]. PMID- 21027727 TI - [Not Available]. PMID- 21027728 TI - [Not Available]. PMID- 21027729 TI - [Not Available]. PMID- 21027730 TI - [Not Available]. PMID- 21027731 TI - [Not Available]. PMID- 21027732 TI - [Not Available]. PMID- 21027733 TI - [Not Available]. PMID- 21027734 TI - [Not Available]. PMID- 21027735 TI - [Not Available]. PMID- 21027736 TI - [Not Available]. PMID- 21027737 TI - [Not Available]. PMID- 21027738 TI - [Not Available]. PMID- 21027739 TI - [Not Available]. PMID- 21027740 TI - [Not Available]. PMID- 21027741 TI - [Not Available]. PMID- 21027742 TI - [Not Available]. PMID- 21027743 TI - [Not Available]. PMID- 21027744 TI - [Not Available]. PMID- 21027745 TI - [Not Available]. PMID- 21027746 TI - [Not Available]. PMID- 21027748 TI - [Not Available]. PMID- 21027747 TI - [Not Available]. PMID- 21027749 TI - Abrief personality appraisal technique for use in interviewing. PMID- 21027750 TI - Dermatitis control. PMID- 21027751 TI - The place of chemotherapy in the treatment of traumatic wounds. PMID- 21027752 TI - Surgical drainage in infected wounds. PMID- 21027753 TI - Fracture problems; fracture therapy by internal and external fixation. PMID- 21027754 TI - Neuropsychiatric aspects of industrial accidents. PMID- 21027755 TI - Prolonged observation on a group of arthritic patients. PMID- 21027756 TI - A study of handicaps in industry. PMID- 21027757 TI - The traumatic neuroses of industry. PMID- 21027758 TI - Practical application of an industrial dental program. PMID- 21027759 TI - The present work of the Industrial health research board of Great Britain. PMID- 21027760 TI - Industrial medicine in the Philippine Islands. PMID- 21027761 TI - The preliminary physical examination for industry. PMID- 21027762 TI - Industry and the general practititoner. PMID- 21027763 TI - The industrial medical centre with particular reference to pre-employment and periodic medical examinations. PMID- 21027764 TI - Dust concentrations in stone crushing operations. PMID- 21027765 TI - Toxicity of some of the newer plastics. PMID- 21027766 TI - Radium dial painting control methods. PMID- 21027767 TI - Report of New Jersey Bureau of Industrial Health July 1, 1994; June 30, 1945. PMID- 21027768 TI - Preventive methods for the prevention of industrial dermatoses. PMID- 21027769 TI - [Not Available]. PMID- 21027770 TI - [Not Available]. PMID- 21027771 TI - [Not Available]. PMID- 21027772 TI - [Not Available]. PMID- 21027773 TI - [Not Available]. PMID- 21027774 TI - [Not Available]. PMID- 21027775 TI - [Not Available]. PMID- 21027776 TI - [Not Available]. PMID- 21027777 TI - [Not Available]. PMID- 21027778 TI - [Not Available]. PMID- 21027779 TI - [Butter analysis]. PMID- 21027780 TI - [Brain abscess etiology]. PMID- 21027781 TI - [Not Available]. PMID- 21027782 TI - [Military Medical Organization]. PMID- 21027783 TI - [Tank warfare]. PMID- 21027784 TI - [Muscle Osteoma]. PMID- 21027785 TI - [Penicillin; tyrothricin]. PMID- 21027786 TI - [Adamantinoma]. PMID- 21027787 TI - [Intestine small: Infarction]. PMID- 21027788 TI - [Xantochromia]. PMID- 21027789 TI - [Not Available]. PMID- 21027790 TI - [Microscope electronic]. PMID- 21027791 TI - [Not Available]. PMID- 21027792 TI - [Water Purificat]. PMID- 21027793 TI - [Leptospirasis grippotyphosa]. PMID- 21027794 TI - [Tonsillitis]. PMID- 21027795 TI - [Not Available]. PMID- 21027796 TI - [Not Available]. PMID- 21027797 TI - [Malaria Serodiagn]. PMID- 21027798 TI - [Not Available]. PMID- 21027799 TI - [Not Available]. PMID- 21027800 TI - [Not Available]. PMID- 21027801 TI - [Inhibiting effect of great doses of gonad-stimulator on the genitals]. PMID- 21027802 TI - [The influence of protracted infusion of pituitary extract on the pituitary, thyroid and sex glands]. PMID- 21027803 TI - [On the development of myelinic membrane in ontogenesis]. PMID- 21027804 TI - [On the chromatophores of the pia mater in man]. PMID- 21027805 TI - [Adsorptive function of the reticulo-endothelial system in virus infections (infectious encephalomyelitis and infectious anemia in horses)]. PMID- 21027806 TI - [The influence of anaphylactic shock on the course of neurodystrophic processes]. PMID- 21027807 TI - [Concerning the action of fragments of vitamin A molecules]. PMID- 21027808 TI - [On the mechanism of secondary hypotony under adrenalinic shock]. PMID- 21027809 TI - [Changes of cerebrospinal fluid and blood in spring-estival encephalitis; changes of the pressure, morphological composition, proteinic colloidal reactions of cerebrospinal fluid in the chronic stage of the disease]. PMID- 21027810 TI - [Oscillations of venous pressure in disturbances of brain vascularization, evoked by meteorological displacements]. PMID- 21027811 TI - [The effect of reduced barometric pressure on the content of diaminoxidase (histaminase) in animal tissue]. PMID- 21027812 TI - [Biocurrents of the brain under conditions of reduced barometric pressure]. PMID- 21027813 TI - [Precommissurial potential in the electrocardiogram]. PMID- 21027814 TI - [Contribution to the physiology of nerve endings of skeleton muscle; on the action of curare on the nerve endings of skeleton muscle]. PMID- 21027815 TI - [On the relationship of electrodiagnosis and chronaxia measurement in nerve trauma of the upper limb]. PMID- 21027816 TI - [On the mechanism of repercussive changes in motor chronaxia of muscle]. PMID- 21027817 TI - [Duration of the refractory phase of the neuro-muscular apparatus under rhythmical stimulation]. PMID- 21027818 TI - [Control of heart fibrillation by means of condensatory discharges of subthreshold power]. PMID- 21027819 TI - [The content of acetylcholine-like substances and cholinesterase in the central nervous system of castrated rats]. PMID- 21027820 TI - [Combined effect of adenosintriphosphate, acetylcholine and the ions of potassium, calcium and magnesium on muscle]. PMID- 21027821 TI - [On the role of the liver in self-regulation of the blood sugar level; the influence of the nervous system on liver function]. PMID- 21027822 TI - [Ascorbigen, a form of ascorbic acid]. PMID- 21027823 TI - [On certain peculiarities of the carcinogenic action of o-amidoazotoluol]. PMID- 21027824 TI - [On the mechanism of the regulatory influence of the extracardial nerves on the heart; correlation of polarizational and humoral factors of heart activity regulation]. PMID- 21027825 TI - [On the mechanism of the action of potassium on nerve refractoriness]. PMID- 21027826 TI - [On the effect of vegetative poisons on phagocytosis in the organism]. PMID- 21027827 TI - [The role of the carotid sinus in antibody formation]. PMID- 21027828 TI - [The nervous factor in relation to sensitization]. PMID- 21027829 TI - [On the peculiarities of the electromyogram in vegetative asymmetry as a result of cranio-cerebral trauma]. PMID- 21027830 TI - [Electroencephalographic examination in posttraumatic epilepsy]. PMID- 21027831 TI - [Further investigation of the thermodynamics of the subarachnoid cerebrospinal fluid by means of thermoelectric measurement, in trauma of the spinal cord]. PMID- 21027832 TI - [On morphological changes in the nerve cell in experimental traumatic shock]. PMID- 21027833 TI - [The calcium content of brain tissue under narcosis]. PMID- 21027834 TI - [The influence of aqueous extracts from conserved skin on the healing of ulcers and wounds]. PMID- 21027835 TI - [The effect of juniper oil and its derivatives on wound healing]. PMID- 21027836 TI - [New data on the action of bromine salts on the thyroid]. PMID- 21027838 TI - [The morphological expression of compensation in the islands of Langerhans]. PMID- 21027837 TI - [The influence of adrenalin and insulin on thermoregulation in childhood]. PMID- 21027839 TI - [On the mechanism of growth of secretory epithelium of the breast]. PMID- 21027840 TI - [Histophysiological peculiarities of the Sertoli stratum in the caniculi seminales]. PMID- 21027841 TI - [The physiology and pathology of the excretory function of the small intestine; excretion of chlorine with intestinal juice]. PMID- 21027842 TI - [On the quantitative relation between concentration of penicillin and its electrokinetic effect]. PMID- 21027843 TI - [On the peculiarities of the blood supply of the adrenals]. PMID- 21027844 TI - [Study of horse fatigue on change of step length]. PMID- 21027845 TI - [Not Available]. PMID- 21027846 TI - [Not Available]. PMID- 21027847 TI - Subphrenic abscess; report of cases. PMID- 21027848 TI - Report of a case of typhus fever. PMID- 21027849 TI - [Not Available]. PMID- 21027850 TI - [Not Available]. PMID- 21027851 TI - [Not Available]. PMID- 21027853 TI - [Not Available]. PMID- 21027852 TI - [Not Available]. PMID- 21027854 TI - [Not Available]. PMID- 21027855 TI - [Not Available]. PMID- 21027856 TI - [Not Available]. PMID- 21027857 TI - [Not Available]. PMID- 21027858 TI - [Not Available]. PMID- 21027859 TI - Cross-infection in children's wards. PMID- 21027860 TI - Nutrition in Vienna in November, 1945. PMID- 21027862 TI - Difference in the effect of scopolamine on peroral and subcutaneous administration. PMID- 21027861 TI - The ionization of penicillin. PMID- 21027863 TI - Carcinoma of the rectum in sisters. PMID- 21027864 TI - Small-bowel obstruction due to dried fruit. PMID- 21027865 TI - MEDICAL School, University of Southern California. PMID- 21027866 TI - COUNTY General Hospital. PMID- 21027867 TI - COFFEY-HUMBER cancer treatment. PMID- 21027868 TI - BROTHER ISAIAH and Miracle Hill. PMID- 21027869 TI - The library of the Association. PMID- 21027870 TI - The meaning of geriatrics. PMID- 21027871 TI - Nutrition in relation to geriatrics. PMID- 21027872 TI - Diabetes and geriatrics. PMID- 21027873 TI - Coronary artery disease in the ageing. PMID- 21027874 TI - Pneumonia in the aged. PMID- 21027875 TI - Emphysema and chronic bronchitis in the aged. PMID- 21027876 TI - Infectious diseases in old age; their incidence, clinical characteristics and therapy. PMID- 21027877 TI - Management of nephritis in the elderly. PMID- 21027878 TI - Arthritis in old age. PMID- 21027879 TI - Common disorders of the aging skin. PMID- 21027880 TI - Certain aspects of gynecology as related to geriatrics. PMID- 21027881 TI - Surgery in the aged. PMID- 21027882 TI - The prostatic patient today. PMID- 21027883 TI - Rectal cancer. PMID- 21027884 TI - Psychiatric disorders of the senium. PMID- 21027886 TI - How a marriage guidance centre works. PMID- 21027885 TI - The periodic health inventory. PMID- 21027887 TI - New treatment of sepsis in the U.S.S.R. PMID- 21027888 TI - Wisdom in dreams. PMID- 21027889 TI - The treatment of empyema and lung abscess by a Mikulicz pack. PMID- 21027890 TI - Sickle cell disease in the Balovale District of Northern Rhodesia. PMID- 21027891 TI - Jaundice in Goans. PMID- 21027892 TI - TETMOSOL treatment of scabies. PMID- 21027893 TI - [Vagina artificialis]. PMID- 21027894 TI - [Preliminary benzedrinization in electric and azozol convulsive treatment and some observations on different convulsive mechanisms]. PMID- 21027895 TI - [The typhoid form of infectious mononucleosis]. PMID- 21027896 TI - [Hemiplegia as a complication in acute bacterial dysentery]. PMID- 21027897 TI - [The relationship between eosinophilic erythredema and filariasis]. PMID- 21027898 TI - [The push test; manual manipulation as a diagnostic aid in the radiological differentiation of intraabdominal calcifications, especially renal calculi]. PMID- 21027899 TI - [Subacute bacterial endocarditis]. PMID- 21027900 TI - [A case of acute haemorrhagic pericarditis; recovery following aspiration and penicillin treatment]. PMID- 21027901 TI - [An outbreak of conjunctivitis in man associated with the virus of Newcastle disease]. PMID- 21027902 TI - [An answer to the remarks of F. Mandl on my paper on a new method in the operation of gigantic spleens]. PMID- 21027903 TI - [The question of immunization in infants]. PMID- 21027904 TI - [From my clinical experience]. PMID- 21027905 TI - [The problem of chronically ill patients in the hospital]. PMID- 21027907 TI - [URTICARIA pigmentosa]. PMID- 21027906 TI - [NEWCASTLE disease in men]. PMID- 21027908 TI - [ACTINOMYCOSIS]. PMID- 21027909 TI - [GRANULOMA annulare]. PMID- 21027910 TI - [Behcet's triple syndrom]. PMID- 21027911 TI - [A new method of anterior colporraphy]. PMID- 21027912 TI - [The tissue culture of L. bodies of L. donovani and L. infantum from flagellates]. PMID- 21027914 TI - [From my clinical experience]. PMID- 21027913 TI - [Infectious skin diseases in infancy]. PMID- 21027915 TI - The reactions of children to subcutaneous and intracutaneous immunization against typhoid. PMID- 21027916 TI - TREATMENT of early syphilis with penicillin. PMID- 21027917 TI - CHANGING character of commercial penicillin, with suggestions as to the use of penicillin in syphilis. PMID- 21027918 TI - The protective effect of vaccination against epidemic influenza B. PMID- 21027919 TI - Curare in the treatment of acute poliomyelitis. PMID- 21027920 TI - Effect of para-aminobenzoic acid in tsutsugamushi disease. PMID- 21027921 TI - The use of neostigmine in the treatment of the Guillain-Barre syndrome. PMID- 21027922 TI - EYE discomfort caused by improperly shielded black light ultraviolet lamps. PMID- 21027923 TI - Coronary occlusion and myocardial infarction. PMID- 21027924 TI - Trends in the care of the psychiatric case. PMID- 21027925 TI - The role of secondary closures in the management of war wounds. PMID- 21027926 TI - Periarteritis nodosum and Wilm's tumor; case report. PMID- 21027927 TI - Reflex shortening of the esophagus in the experimental animal with the production of esophageal hiatus hernia. PMID- 21027928 TI - A comparison between the values for plasma or serum protein as obtained by the specific gravity and the micro-Kjeldahl methods. PMID- 21027929 TI - Studies on streptomycin. PMID- 21027930 TI - Studies on streptomycin; blood levels and urinary excretion in man and animals. PMID- 21027931 TI - A study of the diffusion of penicillin across the ser ous membranes of joint cavities. PMID- 21027932 TI - Outbreak of hemolytic streptococcus throat infection controlled by sulfadiazine. PMID- 21027933 TI - The serologic diagnosis of endemic typhus; the incidence and titer of complement fixing antibodies in random samples of the population in endemic and nonendemic typhus areas. PMID- 21027934 TI - Interpretation of findings in the cerebrospinal fluid; the technique and systematic interpretation of the albumin-globulin ratio in cerebrospinal fluids. PMID- 21027935 TI - The influence of dimethylaminoethyl benzhydryl ether hydrochloride (benadryl) upon normal persons and upon those suffering from disturbances of the autonomic nervous system. PMID- 21027936 TI - Application of the Rh blood types and Hr factor in disputed parentage. PMID- 21027937 TI - The relation of physiologic variables to circulation time. PMID- 21027938 TI - A primary standard for the colorimetric determination of hemoglobin. PMID- 21027939 TI - A simple electrocardiograph contact electrode for use with the smaller laboratory animal. PMID- 21027940 TI - A new type of glass cage for metabolism studies. PMID- 21027941 TI - An isolated heart perfusion system adapted to the determination of nongaseous metabolities; with sample data upon the isolated monkey heart. PMID- 21027942 TI - D.D.T. in public health. PMID- 21027943 TI - The aetiology, investigation and treatment of leucorrhea. PMID- 21027944 TI - Laboratory tests for pregnancy. PMID- 21027945 TI - Face masks in theatre asepsis. PMID- 21027946 TI - Skin asepsis in the operating theatre. PMID- 21027947 TI - Showdown on political medicine. PMID- 21027948 TI - Endometriosis and pregnancy. PMID- 21027949 TI - Cholera epidemic among prisoners-of-war in Siam. PMID- 21027950 TI - Thyrotoxicosis treated with thiouracil and methyl thiouracil. PMID- 21027951 TI - Fowler's position. PMID- 21027952 TI - Dental caries; effect of carbohydrate supplements on susceptibility of infants. PMID- 21027953 TI - Histiocytic medullary reticulosis; a case without lymphadenopathy. PMID- 21027954 TI - Pyloric obstruction by a mass of asphalt. PMID- 21027955 TI - The second biological revolution. PMID- 21027956 TI - Pulmonary tuberculosis among British prisoners in Germany. PMID- 21027957 TI - Emergency Pathology Service. PMID- 21027958 TI - The pre- and post-operative treatment of squint. PMID- 21027959 TI - Ulcers of the cornea and their treatment. PMID- 21027960 TI - The clinical value of rectal temperature readings; a comparison with the oral method. PMID- 21027961 TI - Ureteral obstruction secondary to seminoma of testis. PMID- 21027962 TI - Report of a case of squamous carcinoma of the renal pelvis. PMID- 21027963 TI - Teratoma testis. PMID- 21027964 TI - Experience with urinary calculi and crystaluria in the southwest Pacific. PMID- 21027965 TI - Dieto-metabolic urology. PMID- 21027966 TI - Arthritic syndromes; Reiter's disease followed by endocarditis and lupus erythematosus disseminatus after sulfathiazole treatment. PMID- 21027967 TI - The specific diagnosis of rheumatoid arthritis. PMID- 21027968 TI - The relation of the study of the hand to psychosomatic medicine. PMID- 21027969 TI - The electrical pattern of the superior brain. PMID- 21027970 TI - Sitophobia and inanition, and their treatment. PMID- 21027971 TI - Glycerine and penicillin. PMID- 21027973 TI - [Advances in restorative surgery]. PMID- 21027972 TI - An unusual case of phenobarbital poisoning. PMID- 21027974 TI - [Errors concerning organization of work of a dressing room]. PMID- 21027975 TI - [The care of the wounded in gunshot lesions of the thorax]. PMID- 21027976 TI - [The work of a public health nurse, with reference to the welfare of pregnant and nursing women in industry]. PMID- 21027977 TI - [The use of massage in pediatrics]. PMID- 21027978 TI - [The nurse in sanitary-defense work in schools]. PMID- 21027979 TI - [Cancer of the cervix]. PMID- 21027980 TI - [Cancer of the lower lip]. PMID- 21027981 TI - [The nurse in chemical industry]. PMID- 21027982 TI - [How to organize bath and shower on a collective farm]. PMID- 21027984 TI - [The new drugs]. PMID- 21027983 TI - [Possible errors and complications in blood transfusions]. PMID- 21027985 TI - [Receiving children in children's homes]. PMID- 21027986 TI - [On improving the qualification standards of medical personnel in the middle grades]. PMID- 21027987 TI - [Not Available]. PMID- 21027988 TI - [Not Available]. PMID- 21027989 TI - [Not Available]. PMID- 21027990 TI - [Not Available]. PMID- 21027991 TI - [Not Available]. PMID- 21027992 TI - [Not Available]. PMID- 21027993 TI - Nutritional status of aircraft workers in Southern California: effects of vitamin supplementation on clinical, instrumental, and laboratory findings, and symptoms. PMID- 21027994 TI - Urbanization in Latin America. PMID- 21027995 TI - Low-sodium diet and free fluid intake in the treatment of congestive heart failure; a preliminary report. PMID- 21027996 TI - Alcohol in the treatment of angina pectoris. PMID- 21027997 TI - Spontaneous hematoma of the abdominal wall in pregnancy; report of a case. PMID- 21027998 TI - Research in physical medicine. PMID- 21028000 TI - Pulmonary embolism, massive, bilateral. PMID- 21027999 TI - Pericarditis, acute, fibrinous. PMID- 21028002 TI - Granuloma inguinale: a proctologic consideration. PMID- 21028001 TI - Multiple peritoneal autotransplantation of splenic tissue following traumatic rupture of the spleen. PMID- 21028003 TI - Subacute bacterial endocarditis: mitral valve; splenic infarcts, with rupture of spleen. PMID- 21028004 TI - [A statistical study of antirabic inoculations at Pasteur Institute, Shanghai]. PMID- 21028005 TI - [The blood prothrombin level in pulmonary tuberculosis]. PMID- 21028006 TI - [Revision thoracoplasty]. PMID- 21028007 TI - [Aspiration method for cavity in pulmonary tuberculosis]. PMID- 21028009 TI - [Blood transfusion in children]. PMID- 21028008 TI - [Iridencleisis in the treatment of anterior staphyloma]. PMID- 21028010 TI - [Eclampsia and heatstroke]. PMID- 21028011 TI - [A case of uterogestation deformans]. PMID- 21028012 TI - [Bell's palsy from dental infection]. PMID- 21028013 TI - [Clinical review of penicillin therapy]. PMID- 21028014 TI - Further studies on the estrogen-progesterone treatment of habitual abortion. PMID- 21028015 TI - The readjustment problems of the discharged soldier. PMID- 21028016 TI - Hematuria. PMID- 21028017 TI - Chronic hypoplastic anemia of the newborn; report of a case with apparent recovery. PMID- 21028018 TI - Prepayment health service plans for Farm Security Administration borrowers in North Carolina. PMID- 21028019 TI - Cortical atrophy of the adrenal glands. PMID- 21028020 TI - Lung abscess, empyema and mediastinal carcinoma; a case history. PMID- 21028021 TI - Caudal analgesia; a procedure of merit in rural obstetrical practice. PMID- 21028022 TI - Modern treatment of some communicable diseases. PMID- 21028023 TI - Simultaneous perforations of two separate duodenal ulcers. PMID- 21028024 TI - A community rheumatic fever program. PMID- 21028025 TI - Penicillin by inhalation. PMID- 21028027 TI - Pathology of talc pneumoconiosis with report of an autopsy. PMID- 21028026 TI - Dr. Samuel Guthrie and the discovery of chloroform. PMID- 21028028 TI - Case report. [Appendix, foreign bodies]. PMID- 21028029 TI - Common difficulties in the diagnosis and treatment of cutaneous diseases. PMID- 21028031 TI - Urticaria and its treatment. PMID- 21028030 TI - Dermatoses of the menopause. PMID- 21028032 TI - The treatment of seborrhoeic dermatitis. PMID- 21028033 TI - Ointment bases. PMID- 21028034 TI - Radio-active substances in the treatment of diseases of the skin. PMID- 21028035 TI - Convalescence after head injuries. PMID- 21028036 TI - Protein hydrolysate therapy. PMID- 21028037 TI - The hypopietic patient. PMID- 21028038 TI - Meniere's disease. PMID- 21028039 TI - Renal disease, and its treatment. PMID- 21028040 TI - [Not Available]. PMID- 21028042 TI - The skeleton in forensic medicine. PMID- 21028041 TI - [Not Available]. PMID- 21028043 TI - Homogenous grafts in the repair of peripheral nerve lesions in man. PMID- 21028044 TI - A bullet embolus to the left femoral artery following thoracic gunshot wound. PMID- 21028045 TI - The value of sympathectomy in the treatment of peripheral vascular sclerosis. PMID- 21028046 TI - Chorionic gonadotrophin in the diagnosis of testicular tumors. PMID- 21028047 TI - Extensive destruction of the brain in eclampsia. PMID- 21028048 TI - Treatment of subacute bacterial endocarditis. PMID- 21028049 TI - The cardiac gross and microscopic pathologic anatomy in 9 cases of subacute bacterial endocarditis treated with penicillin. PMID- 21028050 TI - [Not Available]. PMID- 21028051 TI - [Not Available]. PMID- 21028052 TI - [Not Available]. PMID- 21028053 TI - [Not Available]. PMID- 21028054 TI - [Not Available]. PMID- 21028055 TI - [Not Available]. PMID- 21028056 TI - [Not Available]. PMID- 21028057 TI - [Not Available]. PMID- 21028058 TI - [Not Available]. PMID- 21028059 TI - [Not Available]. PMID- 21028060 TI - [Not Available]. PMID- 21028062 TI - [Not Available]. PMID- 21028061 TI - [Not Available]. PMID- 21028063 TI - [Not Available]. PMID- 21028064 TI - [Not Available]. PMID- 21028065 TI - [Not Available]. PMID- 21028066 TI - [Not Available]. PMID- 21028067 TI - [Not Available]. PMID- 21028068 TI - [Not Available]. PMID- 21028069 TI - [Not Available]. PMID- 21028070 TI - [Not Available]. PMID- 21028071 TI - [Not Available]. PMID- 21028072 TI - [Not Available]. PMID- 21028073 TI - [Not Available]. PMID- 21028074 TI - [Not Available]. PMID- 21028075 TI - [Not Available]. PMID- 21028076 TI - [Not Available]. PMID- 21028077 TI - [Not Available]. PMID- 21028078 TI - [Not Available]. PMID- 21028079 TI - [Not Available]. PMID- 21028080 TI - [Not Available]. PMID- 21028081 TI - [Not Available]. PMID- 21028082 TI - [Not Available]. PMID- 21028083 TI - [Not Available]. PMID- 21028084 TI - [Not Available]. PMID- 21028085 TI - [Not Available]. PMID- 21028086 TI - [Not Available]. PMID- 21028087 TI - [Not Available]. PMID- 21028088 TI - [Not Available]. PMID- 21028090 TI - [Not Available]. PMID- 21028091 TI - [Not Available]. PMID- 21028089 TI - [Not Available]. PMID- 21028092 TI - [Not Available]. PMID- 21028093 TI - [Not Available]. PMID- 21028094 TI - [Not Available]. PMID- 21028095 TI - BARBED wire and beri-beri. PMID- 21028096 TI - [Not Available]. PMID- 21028097 TI - [Not Available]. PMID- 21028098 TI - [Not Available]. PMID- 21028099 TI - [Not Available]. PMID- 21028100 TI - [Not Available]. PMID- 21028101 TI - [Not Available]. PMID- 21028102 TI - [Not Available]. PMID- 21028103 TI - [Not Available]. PMID- 21028104 TI - [Not Available]. PMID- 21028105 TI - [Not Available]. PMID- 21028106 TI - The Arnold-Chiari malformation; a morphogenetic study. PMID- 21028107 TI - Results of thyroidectomy in older patients; a postexamination. PMID- 21028108 TI - Anatomical problems relative to the traumatic surgery of muscle. PMID- 21028109 TI - [Not Available]. PMID- 21028110 TI - [Not Available]. PMID- 21028111 TI - [Not Available]. PMID- 21028112 TI - [Not Available]. PMID- 21028113 TI - [Not Available]. PMID- 21028114 TI - [Not Available]. PMID- 21028115 TI - [Not Available]. PMID- 21028116 TI - [Not Available]. PMID- 21028117 TI - [Not Available]. PMID- 21028118 TI - [Not Available]. PMID- 21028119 TI - [Not Available]. PMID- 21028120 TI - [Not Available]. PMID- 21028121 TI - [Not Available]. PMID- 21028122 TI - [Not Available]. PMID- 21028123 TI - [Not Available]. PMID- 21028124 TI - [Not Available]. PMID- 21028125 TI - [Not Available]. PMID- 21028126 TI - [Not Available]. PMID- 21028127 TI - [Not Available]. PMID- 21028128 TI - [Not Available]. PMID- 21028129 TI - ORGANISATION of scientific and industrial research. PMID- 21028130 TI - The Egyptian Academy of Sciences. PMID- 21028131 TI - Transport of water and salts through plant tissues. PMID- 21028132 TI - PERSONNEL of museums. PMID- 21028133 TI - Biological action of radiations. PMID- 21028134 TI - Selective hydrogenation of polyethenoid fatty compounds: a possible mechanism. PMID- 21028135 TI - Effect of unsaturated fatty acids on the acid production of Lactobacillus helveticus. PMID- 21028136 TI - Excretion of lead in the bile. PMID- 21028137 TI - Structure of the cuticle of wool. PMID- 21028138 TI - Formation of polymers in textile fibres. PMID- 21028139 TI - Origin of the first European potatoes and their reaction to length of day. PMID- 21028141 TI - [Progress of soviet visibilimetry]. PMID- 21028140 TI - Stage of determination of vertebrae in teleostean fishes. PMID- 21028142 TI - [Articulate speech and thinking in the life of primitive man]. PMID- 21028143 TI - [Botany and pharmacology]. PMID- 21028144 TI - [THYROIDECTOMY and low temperature]. PMID- 21028145 TI - [URANIUM in the animal body]. PMID- 21028146 TI - [GLOBULIN as a coagulant]. PMID- 21028148 TI - [RESULT of the loss of iodine or the toxic agent in goitre]. PMID- 21028147 TI - [THE SIGNIFICANCE of diet in reproduction]. PMID- 21028149 TI - [AMOUNT of vitamin C in the fruit of the wild rose in connection with polyploidy]. PMID- 21028150 TI - Medical research mission to the Soviet Union. PMID- 21028151 TI - Acetylcholine synthesis. PMID- 21028152 TI - Granulocytopenia and anemia in rats fed diets of low case in content. PMID- 21028153 TI - The presence and significance of a leukopenic factor in inflammatory exudates. PMID- 21028154 TI - The comparative toxicity of thiourea to four mutants of Drosophila melanogaster. PMID- 21028155 TI - The effect of DDT on cutaneous sensations in man. PMID- 21028156 TI - Work of the International Commission on Zoological Nomenclature. PMID- 21028157 TI - Dorsal root potentials of the spinal cord. PMID- 21028158 TI - Influence of harmonic content on wave forms of the human electroencephalogram. PMID- 21028159 TI - An inhibitory mechanism in the bulbar reticular formation. PMID- 21028160 TI - Morphology and conduction of bipolar dorsal root ganglion cells of selachian fishes. PMID- 21028161 TI - A midbrain mechanism for facio-vocal activity. PMID- 21028162 TI - Central effects of centripetal impulses in axons of spinal ventral roots. PMID- 21028163 TI - Tonic and reflex functions of medullary sympathetic cardiovascular centers. PMID- 21028164 TI - Brain stem facilitation of cortical motor response. PMID- 21028165 TI - Properties of maximal seizures, and their alteration by anticonvulant drugs and other agents. PMID- 21028166 TI - Transmission of impulses in peripheral nerves treated with di-isopropyl fluorphosphate. PMID- 21028167 TI - Effect of di-isopropyl fluorphosphate on action potential and choline esterase of nerve. PMID- 21028168 TI - Emotional factors in skin disorders. PMID- 21028169 TI - Deformities of the nasal septum; a cause of systemic disorders. PMID- 21028170 TI - The mock accident in first-aid training; fracture of the femur. PMID- 21028172 TI - The nursing care of the premature baby. PMID- 21028171 TI - The psychological relationship between theory and practice. PMID- 21028173 TI - Notes on Public health nursing in relation to illness. PMID- 21028174 TI - Operating a Mothers' Milk Bureau. PMID- 21028175 TI - Epidemics can be disasters, too. PMID- 21028176 TI - Accident prevention; an integration unit. PMID- 21028177 TI - Observation period in a mental institution. PMID- 21028178 TI - [Not Available]. PMID- 21028179 TI - [Not Available]. PMID- 21028180 TI - [Not Available]. PMID- 21028181 TI - An unpigmented primary tumour of the optic disc; a contribution to the knowledge of the phakomata of the eye. PMID- 21028182 TI - Conjunctival haemorrhage due to an infection of Newcastle virus of fowls in man; laboratory and contact infection. PMID- 21028183 TI - History of ophthalmology through the ages. PMID- 21028184 TI - Bitemporal hemianopia. PMID- 21028185 TI - Quinine amblyopia. PMID- 21028187 TI - Lens efficiency; a clinical concept. PMID- 21028186 TI - Necessity of an international study centre of trachoma. PMID- 21028188 TI - Ophthalmic problems and visual standards in industry. PMID- 21028189 TI - Cancer of the larynx; five year results of concentration radiotherapy. PMID- 21028190 TI - Wartime laryngeal injuries. PMID- 21028191 TI - Chronic dacryocystitis: its transapertural approach. PMID- 21028192 TI - Aerohematoma of the sinuses. PMID- 21028193 TI - Otitis media; a comparative study of the results obtained in therapy before and after the introduction of the sulfonamide compounds. PMID- 21028195 TI - Apical petrositis. PMID- 21028194 TI - Excision of superior maxilla and ethmoid labyrinth. PMID- 21028196 TI - Effect of emotions on the hydrogen ion concentration of nasal secretion in situ. PMID- 21028197 TI - Healing of fistulas of the human labyrinth. PMID- 21028198 TI - The treatment of chronic otitis media. PMID- 21028199 TI - The treatment of chronic otitis media. PMID- 21028200 TI - Operative treatment of chronic otitis media. PMID- 21028201 TI - Local chemotherapy in paranasal sinusitis. PMID- 21028202 TI - Fatal Actinomyces infection of the middle ear. PMID- 21028203 TI - Allergy in otorhinolaryngology and ophthalmology; a review of the recent current literature. PMID- 21028204 TI - The selection of hearing aids. PMID- 21028205 TI - The role of sinusitis in eye pathology. PMID- 21028206 TI - Focal infection in the pharynx. PMID- 21028207 TI - [Combined wounds of the frontal sinus and brain]. PMID- 21028208 TI - [On the morbid anatomy and therapeutics of gunshot lesions of the paranasal sinus]. PMID- 21028209 TI - [Gunshot wounds of the paranasal sinus and their treatment at Army stations]. PMID- 21028210 TI - [On surgical treatment of combined gunshot damages of the paranasal sinus and adjacent cranial bones]. PMID- 21028211 TI - [On gunshot lesions of the maxillary sinus]. PMID- 21028212 TI - [On combined gunshot wounds of the jaws and ORL organs]. PMID- 21028213 TI - [On foreign bodies of the paranasal sinus]. PMID- 21028214 TI - [On local anesthesia in surgery of the tympanic membrane and middle ear]. PMID- 21028215 TI - [Concerning classification and treatment of gunshot lesions of the mastoid process]. PMID- 21028216 TI - [On histological changes in gunshot trauma of the mastoid process]. PMID- 21028217 TI - [A case of removal of a bullet from the left retromandibular fossa]. PMID- 21028218 TI - [Contribution to the use of Bogomoletz's antireticular cytotoxic serum in ozena and traumatic perichondritis of the larynx]. PMID- 21028219 TI - [Experimental treatment of chronic purulent otitis with gramicidin]. PMID- 21028220 TI - [Experimental treatment of ORL purulent wounds with gramicidin]. PMID- 21028221 TI - [Development of deep-toned speech in patients with excised larynx]. PMID- 21028222 TI - Is speech teaching a failure? PMID- 21028223 TI - The speech vocabulary of young deaf children. PMID- 21028224 TI - AUSTRALIAN rubella babies. PMID- 21028225 TI - Auricular training at Hoff Hospital. PMID- 21028226 TI - Odontogenic tumors: classification based on observations of the epithelial, mesenchymal, and mixed varieties. PMID- 21028227 TI - Atypical lichen planus. PMID- 21028228 TI - Coexistent pulmonary asbestosis and sarcoidosis. PMID- 21028229 TI - Xanthomatosis of the arterial media in a dog. PMID- 21028231 TI - Dysgerminoma of the ovary. PMID- 21028232 TI - Obliterative cerebral arteriosclerosis; a characteristic vascular syndrome. PMID- 21028230 TI - Malignant granulosa cell tumor with pseudotubercles. PMID- 21028233 TI - The central nervous system in pneumonia (nonsuppurative pneumonic encephalitis); a pathologic study. PMID- 21028234 TI - Adenomatoid transformation of the glomerular capsular epithelium. PMID- 21028235 TI - Bismuth pigmentation; its histochemical identification. PMID- 21028236 TI - Ossifying cartilage and thrombi in the hearts of rats. PMID- 21028237 TI - Anomalous portal vein in mice occasionally causing intestinal infarction. PMID- 21028238 TI - The beta granules in the islets of Langerhans in diabetes mellitus. PMID- 21028239 TI - The pathogenesis of tuberous bone formation in the lungs. PMID- 21028240 TI - Crystalline ester cholesterol an irritant. PMID- 21028241 TI - Tumors of the testis. PMID- 21028242 TI - Etiologic factors in patients with carcinoma of the penis and in control groups. PMID- 21028243 TI - Angiomatoid changes in the genital organs with and without tumor formation. PMID- 21028244 TI - Examination of sputum for cancer cells and particles; review of literature and case reports. PMID- 21028245 TI - The in vivo sensitivity to streptomycin of recently isolated strains of human tubercle bacilli. PMID- 21028246 TI - The effect of streptomycin on the histopathology of human tuberculosis. PMID- 21028247 TI - Influence of penicillin in subacute bacterial endocarditis. PMID- 21028248 TI - The effects of radioactive phosphorus (P32) on the malignant lymphomas. PMID- 21028249 TI - On the nature and general pathologic significance of granulomatous inflammation. PMID- 21028250 TI - Granulomata of unknown etiology associated with periarteritis nodosa; report of two cases. PMID- 21028251 TI - Perineuritic and polymyositic granulomatous nodules in rheumatoid arthritis. PMID- 21028252 TI - The venereal granulomas of the penis. PMID- 21028253 TI - Disseminated granuloma venereum. PMID- 21028254 TI - Development and pathognomonic evaluation of the Sternberg-Dorothy Reed cell. PMID- 21028255 TI - Visceral lesions of acute infectious mononucleosis; a report of two cases with fatal spontaneous rupture of the spleen. PMID- 21028256 TI - Systemic nonlipoid reticulo-endothelial granuloma (Letterer-Siwe's type); a pathologic study of four cases. PMID- 21028257 TI - Gaucher's disease; histochemical demonstration of kerasin in tissue. PMID- 21028258 TI - The serodiagnosis of amebiasis; evaluation of the currently available antigens in a quantitatively standardized complement-fixation test. PMID- 21028259 TI - Relative activity of sulfonamides against dysenteric bacilli and their toxic filtrates. PMID- 21028260 TI - Studies on capillary permeability as affected by anoxemia. PMID- 21028261 TI - The influence of age and species on the nephrotoxic action of d1-serine. PMID- 21028262 TI - Experimental streptococcal infections of the chorioallantoic membrane of the embryonic chick. PMID- 21028263 TI - Histopathologic study of anaphylactic shock in identical twins. PMID- 21028264 TI - The nonportal distribution of the trabeculae in dietary cirrhosis of rats and carbon tetrachloride cirrhosis of rats and guinea-pigs. PMID- 21028265 TI - Observations on the cultivation of Bacterium tularense in embryonated eggs. PMID- 21028266 TI - Extensive destruction of the brain in eclampsia. PMID- 21028267 TI - Contact dermatitis. PMID- 21028268 TI - Antigenicity of proteins in relation to allergy. PMID- 21028269 TI - D.H.E. 45 (dihydroergotamine) in the treatment of allergic megraine. PMID- 21028270 TI - Fleabite reactions; clinical and experimental observations and effect of histamine-azoprotein therapy. PMID- 21028272 TI - Nasal and sputum smears. PMID- 21028271 TI - Determination of penicillin-susceptible strains of bacteria. PMID- 21028273 TI - Hay fever; a review of the literature for 1945. PMID- 21028274 TI - Pathologic aspects of acute epidemic hepatitis, with especial reference to early stages; report of a series of ten cases, including a case in which there was spontaneous rupture of the spleen and six cases of fulminating disease in patients who had been wounded several months previously. PMID- 21028275 TI - Chemical factors and their role in inflammation. PMID- 21028276 TI - Adenocarcinoma of the urachus involving the urinary bladder. PMID- 21028277 TI - Teratoma of the anterior mediastinum in the group of military age; a study of 16 cases, and a review of theories of genesis. PMID- 21028278 TI - Struma ovarii. PMID- 21028279 TI - Hepatic abscess complicating atresia of the small intestine of a newborn infant. PMID- 21028280 TI - The course and pathology of Trypanosoma congolense (Broden) disease of cattle. PMID- 21028281 TI - Trypanosoma congolense (Broden) disease of cattle; the parenchymatous lesion and its relation to the cellular defences. PMID- 21028282 TI - A study of the passively acquired antibody to Tr. foetus in the blood of young calves and its behaviour in agglutination tests and intradermal reactions. PMID- 21028284 TI - Observations on perosis occurring in chicks used for vitamin D3 assay. PMID- 21028283 TI - A radiographic study of the normal development of the hock joint of the fowl. PMID- 21028285 TI - Observations on a possible case of jaagziekte in a sheep in Palestine. PMID- 21028286 TI - State legislation for the education of exceptional children; some basic principles. PMID- 21028287 TI - Curriculum planning for exceptional children. PMID- 21028288 TI - SEGREGATION versus non-segregation of exceptional children. PMID- 21028289 TI - RELATIVE work efficiency of physically disabled industrial workers. PMID- 21028290 TI - The retention of electrolyte during recovery from severe dehydration due to diarrhea. PMID- 21028292 TI - Potassium intoxication; report of an infant surviving a serum potassium level of 12.27 millimoles per liter. PMID- 21028291 TI - The use of potassium chloride in the treatment of the dehydration of diarrhea in infants. PMID- 21028293 TI - Hot baths in the treatment of early infantile paralysis. PMID- 21028294 TI - The use of normal serum gamma globulin antibodies (human) concentrated (immune serum globulin) in the prevention and attenuation of measles. PMID- 21028295 TI - The use of normal serum gamma globulin antibodies (human) concentrated (immune serum globulin) in the treatment of premature infants. PMID- 21028296 TI - Hemolysis from irregular isoagglutinins (cold agglutinins) following treatment for erythroblastosis fetalis. PMID- 21028298 TI - Penicillin in the treatment of childhood gonorrhea. PMID- 21028297 TI - A case of Stevens-Johnson disease (erythema multiforme bullosa) treated with penicillin. PMID- 21028299 TI - Pemphigus, successful treatment with penicillin. PMID- 21028300 TI - Poor eating habits of the runabout child; the role of physiologic anorexia. PMID- 21028301 TI - Tick paralysis in children. PMID- 21028302 TI - Acute infectious urticaria. PMID- 21028303 TI - Enterogenous cyst of the ileocecal region. PMID- 21028304 TI - Mediterranean anemia (Cooley) in a Negro girl. PMID- 21028305 TI - Epidermolysis bullosa hereditaria; report of two cases. PMID- 21028306 TI - Pituitary dwarfism? spontaneous correction. PMID- 21028307 TI - North Carolina study of child health services. PMID- 21028308 TI - Health and welfare services for mothers and children in the Union of the Soviet Socialist Republics. PMID- 21028309 TI - [Not Available]. PMID- 21028310 TI - [Not Available]. PMID- 21028311 TI - [Not Available]. PMID- 21028312 TI - [Not Available]. PMID- 21028313 TI - [Not Available]. PMID- 21028314 TI - Studies on the quantitative determination of the adrenaline content of the blood with the fluorescence method; the normal adrenaline content of the blood in man and animals. PMID- 21028315 TI - On the serviceability of Koppanyi's method for quantitative determination of barbituric acid derivatives in urine. PMID- 21028316 TI - Nicotine-like actions of arecoline. PMID- 21028318 TI - On the relation between goitrogenic effect and chemical constitution. PMID- 21028317 TI - Ether concentration in blood and brain in the early stages of ether narcosis. PMID- 21028319 TI - Renal tubular secretion of sulfonamides and p-aminobenzoic acid. PMID- 21028320 TI - Three antibacterial components in commercial penicillin. PMID- 21028321 TI - The agar cup method for the estimation of penicillin. PMID- 21028322 TI - Mechanism of the variations in the diameter of the abdominal arteries after intravenous injection of adrenaline. PMID- 21028323 TI - The disintegration of standard pills (Pharmacopoea Danica) in the human stomach and in vitro. PMID- 21028324 TI - The pyrogenic effect of Danish penicillin. PMID- 21028325 TI - Experimental studies on the pharmacology of activated charcoal; adsorption power of charcoal in aqueous solutions. PMID- 21028326 TI - Some investigations on the absorption mechanism of protamine insulin. PMID- 21028327 TI - Enzymatic break-down of protamine insulin; further investigations. PMID- 21028328 TI - The influence of the Quakers on Philadelphia institutions. PMID- 21028329 TI - Science today and tomorrow. PMID- 21028330 TI - The age of research in science. PMID- 21028331 TI - Medicine, pharmacy and tomorrow's health. PMID- 21028332 TI - Pharmaceutical sales training and professional relations. PMID- 21028333 TI - What pharmacy should mean to you as pharmacy students. PMID- 21028334 TI - The need for the unification of the medical field. PMID- 21028335 TI - The challenge of pharmaceutical industry to pharmaceutical education. PMID- 21028336 TI - Pre-Columbia healers of Latin America. PMID- 21028337 TI - [Not Available]. PMID- 21028339 TI - [Not Available]. PMID- 21028338 TI - [Not Available]. PMID- 21028341 TI - [Not Available]. PMID- 21028340 TI - [Not Available]. PMID- 21028342 TI - [Not Available]. PMID- 21028343 TI - [Not Available]. PMID- 21028344 TI - [Not Available]. PMID- 21028345 TI - [Pharmacological examination of crystalloid coronillin]. PMID- 21028346 TI - [The effect of Soviet synthetic antimalarial remedies, acriquine and plasmocide, on the nervous system]. PMID- 21028347 TI - [Some data on the pharmacology of certain sulfamide preparations; the action on the isolated heart and on the vessels of the hind limbs of the frog]. PMID- 21028348 TI - [The effect of the fruit of Schizandra chinensis on the spinal centres. PMID- 21028349 TI - [Biochemical changes of the blood and urine in acute intoxication by anilin and other amido- and nitro-compounds of benzol]. PMID- 21028350 TI - [Biochemical changes of the blood and urine in a case of acute anilin poisoning]. PMID- 21028351 TI - [Detoxicating function of the liver and other organs in anilin poisoning]. PMID- 21028352 TI - [Detoxicating function of the liver and other organs in dinitrobenzol poisoning]. PMID- 21028353 TI - [The role of the liver in detoxication of trinitrotoluol]. PMID- 21028354 TI - [The influence of ascorbic acid on the detoxicating function of the organism in anilin poisoning]. PMID- 21028355 TI - [On the action of anilin upon tissue respiration]. PMID- 21028356 TI - [Blood glutathione in chronic experimental anilin poisoning]. PMID- 21028357 TI - [Changes of the alkali reserve and pH of the blood in acute intoxication by amido and nitro-compounds of benzol]. PMID- 21028358 TI - [Oxido-reduction potential of the blood in acute anilin poisoning]. PMID- 21028359 TI - [Pharmacy in the Tuvin autonomous province]. PMID- 21028360 TI - [On the role and services of the soviet village dispensary]. PMID- 21028361 TI - [On the authority of the managers of rural and regional dispensaries]. PMID- 21028362 TI - [New trends in production of pharmaceutical preparations of vegetative raw material]. PMID- 21028363 TI - [The vacuum and spraying methods of drying thermolabile concentrates]. PMID- 21028364 TI - [The work of the All-Union Scientific Chemical-Pharmaceutical Institute during 1944]. PMID- 21028365 TI - [The determination of carotene]. PMID- 21028366 TI - [Sabadilla and the quantitative determination of its infusion alkaloids]. PMID- 21028367 TI - [Qualitative reactions of phenacetin, dulcine, acetanilide and plasmocide]. PMID- 21028368 TI - [The optimal conditions for the drying of primrose leaves]. PMID- 21028369 TI - [The oil from the seeds of wild roses as a source of carotene]. PMID- 21028370 TI - [Concerning the chemical section of the new Pharmacopeia USSR, 8. edition]. PMID- 21028371 TI - Dental caries and sodium fluoride. PMID- 21028372 TI - Occurrence of official drugs in prescriptions. PMID- 21028373 TI - [Not Available]. PMID- 21028374 TI - [Not Available]. PMID- 21028375 TI - The influence of alpha, gamma-dihydroxy-beta, beta-dimethyl-butyric acid on yeast growth. PMID- 21028376 TI - Antivitamin effect of sulfanilamide on Saccharomyces cerevisiae. PMID- 21028377 TI - Antivitamin effect of sulfanilamide on Streptobacterium plantarum. PMID- 21028378 TI - Effect of marfanil on Streptobacterium plantarum, Saccharomyces cerevisiae and Aspergillus niger. PMID- 21028379 TI - Effect of benzoic acid and benzoic acid derivatives on the growth of Streptobacterium plantarum and Saccharomyces cerevisiae. PMID- 21028380 TI - Antivitamin effect of sulfanilamide on Aspergillus niger. PMID- 21028381 TI - The extracellular release of echinochrome. PMID- 21028382 TI - The chemistry of daylight vision. PMID- 21028383 TI - Photolytic lipids from visual pigments. PMID- 21028384 TI - Potassium accumulation in the proximal convoluted tubules of the frog's kidney. PMID- 21028385 TI - Anoxia and brightness discrimination. PMID- 21028386 TI - The intelligence-vocabulary ratio as a measure of temperament. PMID- 21028387 TI - Studies in insulin and metrazol therapy; the differential prognostic value of some psychological tests. PMID- 21028388 TI - Studies in insulin and metrazol therapy; differential effects on some psychological functions. PMID- 21028389 TI - [Not Available]. PMID- 21028391 TI - [Not Available]. PMID- 21028390 TI - [Not Available]. PMID- 21028392 TI - [Not Available]. PMID- 21028393 TI - [Not Available]. PMID- 21028394 TI - The health organisation and biological standardisation. PMID- 21028395 TI - Notes on the international standards for antitoxins and antisera. PMID- 21028396 TI - Notes on the international standards for drugs, hormones and vitamins. PMID- 21028397 TI - UNIFICATION of pharmacopoeias; interim report of the Technical Commission of Pharmacopoeial Experts. PMID- 21028398 TI - [Not Available]. PMID- 21028399 TI - [Not Available]. PMID- 21028400 TI - [Radiation temperature, its determination and employment]. PMID- 21028401 TI - [Concerning the biothermic method of rendering dust harmless]. PMID- 21028402 TI - [The problem of sewerage of populated areas]. PMID- 21028403 TI - [A new method for detecting vapors of tetraethyl lead in the air]. PMID- 21028404 TI - [Instruction of workers in the chemical industry]. PMID- 21028405 TI - [Review of articles regarding practical vitaminology, 1942-44]. PMID- 21028406 TI - [On intestinal bacteria of cold-blooded species of Uzbekistan and their relation to sanitary-bacteriological tests]. PMID- 21028407 TI - [Bacteriophages in water sources of Stalingrad]. PMID- 21028408 TI - [Street accidents involving children and their control]. PMID- 21028409 TI - [Local sanitary legislation]. PMID- 21028410 TI - [Effectiveness of water chlorination under low temperatures]. PMID- 21028411 TI - [A method of adsorbing resinous substances from the conifer]. PMID- 21028412 TI - [On establishing the boundaries of the second zone of sanitary protection of water supply sources]. PMID- 21028413 TI - [Disinfection of water by electrolysis]. PMID- 21028414 TI - [The practical aspect of the use of stimulators]. PMID- 21028415 TI - [Norms in relation to the bacteriology of products of children's milk kitchens]. PMID- 21028416 TI - [Determination of saccharose and lactose in children's milk mixtures]. PMID- 21028418 TI - [The sanitary physician of the railway transport]. PMID- 21028417 TI - [Sanitary protection of the frontiers of the USSR]. PMID- 21028419 TI - [The sanitary physician of the water transport]. PMID- 21028420 TI - [The industrial physician]. PMID- 21028421 TI - [On determining water oxidability]. PMID- 21028422 TI - [Concerning the detection of volatile acids in beverages and food]. PMID- 21028423 TI - The provision of nursery schools. PMID- 21028424 TI - The case for diphtheria immunization. PMID- 21028425 TI - Smallpox in returning servicemen. PMID- 21028426 TI - An appraisal of school health examinations. PMID- 21028427 TI - Medical social work in a public health program. PMID- 21028428 TI - The child and the dentist. PMID- 21028429 TI - Caries inhibition with topical fluorine. PMID- 21028430 TI - Social medicine in a Middle East base. PMID- 21028431 TI - The practical action of D.D.T. PMID- 21028432 TI - Shadowed replicas of tooth surfaces. PMID- 21028433 TI - The preparation of antigens from yolk sacs infected with rickettsiae. PMID- 21028434 TI - The tropical disease education program of the United States Public Health Service. PMID- 21028435 TI - [Not Available]. PMID- 21028436 TI - [Not Available]. PMID- 21028437 TI - [Not Available]. PMID- 21028438 TI - [Concerning formation of norms for the dispensary polyclinic service]. PMID- 21028439 TI - [The tasks next in turn of the anticancerous struggle]. PMID- 21028440 TI - [Dresser and dresser-midwife stations in rural medical service]. PMID- 21028441 TI - [Some questions of organization and work of the sanitary epidemiological station]. PMID- 21028442 TI - [Radiant heating for medical buildings]. PMID- 21028443 TI - [Abbreviated terminology of the finger]. PMID- 21028444 TI - [The liability of medical workers for non-rendering of medical aid]. PMID- 21028445 TI - [Medical history and the soviet press]. PMID- 21028446 TI - Pre-determining effective dosage of copper sulphate in algae control. PMID- 21028447 TI - The use of lime to eliminate small mud balls in filters. PMID- 21028448 TI - Present trends in the sewage works field. PMID- 21028449 TI - High capacity trickling filters; two stage filters. PMID- 21028450 TI - The significance of minor bone injuries. PMID- 21028451 TI - Pulmonary oil embolism. PMID- 21028452 TI - Cancer in childhood. PMID- 21028453 TI - A case of sarcoma of bone treated by radiotherapy. PMID- 21028454 TI - A cutting punch biopsy forceps. PMID- 21028455 TI - The inactivation of viruses by radiations. PMID- 21028456 TI - A condenser chamber measuring apparatus. PMID- 21028457 TI - [Not Available]. PMID- 21028458 TI - [Not Available]. PMID- 21028459 TI - [Not Available]. PMID- 21028460 TI - The Physick-Sellheim principle of extraperitoneal cesarean section; elucidation of a technic based on 175 cases. PMID- 21028461 TI - Saddle block anesthesia. PMID- 21028462 TI - Chronic lumbar backache. PMID- 21028463 TI - Causes of death in burned patients; a report of 23 deaths in 744 burned patients. PMID- 21028464 TI - Contiguous skin flaps for wounds of the extremities. PMID- 21028465 TI - Studies on neuro-muscular dysfunction; neostigmine therapy of chronic disability following fractures; report of 51 cases. PMID- 21028466 TI - Diabetic amputations; amputation of lower extremity in diabetics; analysis of 128 cases. PMID- 21028467 TI - A towel for use in thigh amputations. PMID- 21028468 TI - Treatment of finger fractures, simple and compound. PMID- 21028469 TI - Postoperative hernia following abdominal perineal resection. PMID- 21028470 TI - Unusual foreign body in rectum. PMID- 21028471 TI - Traumatic luxation of the testis. PMID- 21028472 TI - Bilateral branchial cleft cyst. PMID- 21028474 TI - Colostomy clamp. PMID- 21028473 TI - Visible guide for nailing intracapsular femoral neck fractures. PMID- 21028475 TI - New self-retaining retractor. PMID- 21028476 TI - Malformations of the uterus; review of the subject, including embryology, comparative anatomy, diagnosis and report of cases. PMID- 21028477 TI - [Not Available]. PMID- 21028478 TI - [Not Available]. PMID- 21028479 TI - [Not Available]. PMID- 21028480 TI - [Not Available]. PMID- 21028481 TI - [Not Available]. PMID- 21028482 TI - [Not Available]. PMID- 21028483 TI - [Not Available]. PMID- 21028484 TI - [Not Available]. PMID- 21028485 TI - [Not Available]. PMID- 21028486 TI - [Not Available]. PMID- 21028487 TI - [Not Available]. PMID- 21028488 TI - [Not Available]. PMID- 21028489 TI - [Not Available]. PMID- 21028490 TI - [Not Available]. PMID- 21028491 TI - [Not Available]. PMID- 21028492 TI - [Not Available]. PMID- 21028493 TI - [Not Available]. PMID- 21028495 TI - [Not Available]. PMID- 21028494 TI - [Not Available]. PMID- 21028496 TI - [Not Available]. PMID- 21028497 TI - [Not Available]. PMID- 21028498 TI - [Not Available]. PMID- 21028499 TI - [Not Available]. PMID- 21028500 TI - [Not Available]. PMID- 21028501 TI - [Not Available]. PMID- 21028502 TI - [Not Available]. PMID- 21028503 TI - [Not Available]. PMID- 21028504 TI - [Not Available]. PMID- 21028505 TI - [Not Available]. PMID- 21028506 TI - [Not Available]. PMID- 21028507 TI - [Not Available]. PMID- 21028508 TI - Administration of an anesthesia department. PMID- 21028509 TI - An outline of analeptic drugs. PMID- 21028510 TI - The problem of the service-trained anesthetist. PMID- 21028511 TI - [Not Available]. PMID- 21028513 TI - [Not Available]. PMID- 21028512 TI - [Not Available]. PMID- 21028514 TI - [Not Available]. PMID- 21028515 TI - [Not Available]. PMID- 21028517 TI - [Not Available]. PMID- 21028516 TI - [Not Available]. PMID- 21028518 TI - [Not Available]. PMID- 21028519 TI - [Not Available]. PMID- 21028520 TI - [Not Available]. PMID- 21028521 TI - [Not Available]. PMID- 21028522 TI - [Not Available]. PMID- 21028523 TI - [Not Available]. PMID- 21028524 TI - [Not Available]. PMID- 21028525 TI - [Not Available]. PMID- 21028526 TI - [Not Available]. PMID- 21028527 TI - [Not Available]. PMID- 21028528 TI - [Not Available]. PMID- 21028530 TI - [Not Available]. PMID- 21028529 TI - [Not Available]. PMID- 21028531 TI - [Not Available]. PMID- 21028532 TI - [Not Available]. PMID- 21028533 TI - [Not Available]. PMID- 21028534 TI - [Not Available]. PMID- 21028535 TI - [Not Available]. PMID- 21028536 TI - Evolution of neurosurgery through Walter E. Dandy's work. PMID- 21028537 TI - Complete extracapsular excision of tumors of the hypophysis. PMID- 21028538 TI - Cranial nerve surgery in the posterior fossa. PMID- 21028539 TI - The repair of cranial defects by bone grafting. PMID- 21028540 TI - Cephalhematoma deformans; late developments of infantile cephalhematoma. PMID- 21028541 TI - Concussion and contusion. PMID- 21028542 TI - A hypothalamic syndrome and periventricular epilepsy as a late sequel of brain injury. PMID- 21028543 TI - Contralateral, ipsilateral, and bilateral representation of cutaneous receptors in somatic areas I and II of the cerebral cortex of pig, sheep, and other mammals. PMID- 21028544 TI - The surgical treatment of vascular anomalies of the premotor area producing epilepsy. PMID- 21028545 TI - The importance of air studies in a neurosurgical clinic. PMID- 21028546 TI - The innervation of the veins. PMID- 21028547 TI - The practice of surgery in Japanese prison camp hospitals in Burma and Siam. PMID- 21028548 TI - Cerebral fungus following penetrating wounds. PMID- 21028549 TI - Skin diseases in industry. PMID- 21028550 TI - Rehabilitation in the post-war period. PMID- 21028551 TI - Functional job analysis. PMID- 21028552 TI - Sleep posture; its implications. PMID- 21028553 TI - Examination of lead workers. PMID- 21028554 TI - The accurate determination of limb volume. PMID- 21028555 TI - The clinical implications of the Disabled Persons (Employment) Act, 1944. PMID- 21028556 TI - The detection and evolution of adolescent deformities of the spine. PMID- 21028557 TI - Training in physical medicine. PMID- 21028558 TI - Physiotherapy in the treatment of gynaecological disorders. PMID- 21028560 TI - THERAPY of adrenal insufficiency. PMID- 21028559 TI - Peripheral nerve injuries and the physiotherapist. PMID- 21028561 TI - USE of thiouracil. PMID- 21028562 TI - [Not Available]. PMID- 21028563 TI - [Not Available]. PMID- 21028564 TI - [Not Available]. PMID- 21028565 TI - [Not Available]. PMID- 21028566 TI - [Not Available]. PMID- 21028567 TI - [Not Available]. PMID- 21028568 TI - [Not Available]. PMID- 21028570 TI - [Not Available]. PMID- 21028569 TI - [Not Available]. PMID- 21028572 TI - On a fatal case of blackwater fever with pseudo-methaemoglobinemia. PMID- 21028573 TI - Acute rheumatic fever in Eritrea. PMID- 21028571 TI - [Not Available]. PMID- 21028574 TI - [Not Available]. PMID- 21028575 TI - [Not Available]. PMID- 21028576 TI - [Not Available]. PMID- 21028577 TI - [Not Available]. PMID- 21028578 TI - [Not Available]. PMID- 21028579 TI - [Not Available]. PMID- 21028580 TI - [Not Available]. PMID- 21028581 TI - [Not Available]. PMID- 21028582 TI - [Not Available]. PMID- 21028583 TI - [Not Available]. PMID- 21028584 TI - [Not Available]. PMID- 21028585 TI - [Not Available]. PMID- 21028586 TI - [Not Available]. PMID- 21028587 TI - [Not Available]. PMID- 21028588 TI - [Not Available]. PMID- 21028589 TI - [Not Available]. PMID- 21028590 TI - [Not Available]. PMID- 21028592 TI - [Not Available]. PMID- 21028591 TI - [Not Available]. PMID- 21028593 TI - [Not Available]. PMID- 21028594 TI - [Not Available]. PMID- 21028595 TI - [Not Available]. PMID- 21028596 TI - [Not Available]. PMID- 21028597 TI - [Not Available]. PMID- 21028598 TI - [Not Available]. PMID- 21028599 TI - [Not Available]. PMID- 21028600 TI - [Not Available]. PMID- 21028601 TI - [Not Available]. PMID- 21028602 TI - [Not Available]. PMID- 21028604 TI - Medical disorders in East Africa. PMID- 21028603 TI - [Not Available]. PMID- 21028605 TI - Mites (Acarina), a probable factor in the aetiology of spasmodic bronchitis and asthma associated with high eosinophilia. PMID- 21028606 TI - Studies on the venom of South African scorpions (Parabuthus, Hadogenes, Opisthophthalmus) and the preparation of a specific anti-scorpion serum. PMID- 21028607 TI - The control of leprosy among the Azande, Anglo-Egyptian Sudan. PMID- 21028608 TI - Kwashiorkor and ariboflavinosis. PMID- 21028609 TI - Ambulatory treatment of tropical ulcers. PMID- 21028610 TI - Excretion of stilbamidine. PMID- 21028611 TI - [Not Available]. PMID- 21028612 TI - [Not Available]. PMID- 21028613 TI - [Not Available]. PMID- 21028614 TI - [Not Available]. PMID- 21028615 TI - [Not Available]. PMID- 21028616 TI - [Not Available]. PMID- 21028617 TI - [Not Available]. PMID- 21028618 TI - [Not Available]. PMID- 21028619 TI - [Not Available]. PMID- 21028620 TI - [Not Available]. PMID- 21028621 TI - [Not Available]. PMID- 21028622 TI - [Not Available]. PMID- 21028623 TI - [Not Available]. PMID- 21028624 TI - [Not Available]. PMID- 21028625 TI - [Not Available]. PMID- 21028626 TI - [Not Available]. PMID- 21028627 TI - [Not Available]. PMID- 21028628 TI - [Not Available]. PMID- 21028629 TI - [Not Available]. PMID- 21028630 TI - [Not Available]. PMID- 21028631 TI - [Not Available]. PMID- 21028632 TI - [Not Available]. PMID- 21028633 TI - [Not Available]. PMID- 21028634 TI - [Not Available]. PMID- 21028635 TI - [Not Available]. PMID- 21028636 TI - [Not Available]. PMID- 21028637 TI - [Not Available]. PMID- 21028638 TI - Crossed renal ectopia with fusion. PMID- 21028639 TI - Polycystic disease in a solitary kidney. PMID- 21028640 TI - Papilloma of an ectopic kidney; case report, and review of twenty-two tumors in ectopic and ptotic kidneys. PMID- 21028641 TI - Four urological anomalies in one person. PMID- 21028642 TI - Ectopic ureter. PMID- 21028643 TI - Endometriosis of the urinary bladder with report of a case. PMID- 21028644 TI - Cystometry in the study of traumatic neurogenic bladder. PMID- 21028645 TI - Late erosion of shell fragment into the bladder. PMID- 21028646 TI - Cancerous and precancerous lesions of the penis; a clinical and pathological study based on twenty-three cases. PMID- 21028647 TI - Prolapsus of a ureterocele through the urethra; case report. PMID- 21028649 TI - Lymphosarcoma of the testicle; report of a case. PMID- 21028648 TI - Primary melano-epithelioma of female urethra; review of literature; report of three cases. PMID- 21028650 TI - Hemangioma of the testis in an infant. PMID- 21028651 TI - Report of a case of splenic rest in the scrotum. PMID- 21028653 TI - A modification of the Nesbit resectoscope. PMID- 21028652 TI - The prevention of renal complications by the therapeutic employment of sulfonamide mixtures; sulfathiazole-sulfadiazine combination. PMID- 21028654 TI - Fighting "sin in paradise.". PMID- 21028655 TI - The Honolulu myth. PMID- 21028656 TI - PARIS moves to close brothels. PMID- 21028657 TI - NAVY provides social protection for servicemen in Japan. PMID- 21028658 TI - SOCIAL protection needs in peacetime. PMID- 21028659 TI - EUROPE; rapid increase in syphilis during war. PMID- 21028660 TI - The systemic treatment of arsenic poisoning with BAL (2,3-dimercaptopropanol). PMID- 21028661 TI - False positive serologic reactions for syphilis in lymphogranuloma venereum. PMID- 21028662 TI - Studies in syphilis; fibrosis and round cell infiltration of the parenchymatous organs (Warthin) in relation to serodiagnostic findings. PMID- 21028663 TI - The use of smears in the laboratory diagnosis of gonorrhea. PMID- 21028664 TI - [Not Available]. PMID- 21028665 TI - [Not Available]. PMID- 21028666 TI - [Not Available]. PMID- 21028667 TI - [Not Available]. PMID- 21028668 TI - [Cattle disease]. PMID- 21028669 TI - [Not Available]. PMID- 21028670 TI - [Not Available]. PMID- 21028671 TI - [Not Available]. PMID- 21028672 TI - [Not Available]. PMID- 21028673 TI - [Not Available]. PMID- 21028674 TI - [Listerella infection]. PMID- 21028676 TI - Some sources of discontent in Australian veterinary services. PMID- 21028675 TI - Progress in the control of contagious abortion in New Zealand by vaccination. PMID- 21028677 TI - Prophylactic vaccination against infectious laryngo-tracheitis. PMID- 21028678 TI - A specific arthritis with pericarditis affecting horses in Tasmania. PMID- 21028679 TI - A note on the tuberculin test applied to pigs. PMID- 21028680 TI - The occurrence of the pigeon fly (Pseudolynchia canariensis Macq.) in Australia, with a note on Australian Hippoboscidae. PMID- 21028681 TI - The treatment of equine colic. PMID- 21028682 TI - A specific breeding problem of sheep on subterranean clover pastures in Western Australia. PMID- 21028683 TI - A survey of Victorian canine and vulpine parasites; material and methods used in the investigation; Taenia multiceps, Taenia ovis and Echinococcus granulosus. PMID- 21028684 TI - Defective interventricular septum in a calf. PMID- 21028685 TI - New swab for infectious laryngotracheitis vaccination. PMID- 21028686 TI - [Not Available]. PMID- 21028687 TI - [Not Available]. PMID- 21028688 TI - [Not Available]. PMID- 21028689 TI - [Not Available]. PMID- 21028690 TI - [Not Available]. PMID- 21028691 TI - [Not Available]. PMID- 21028692 TI - [Not Available]. PMID- 21028693 TI - [Not Available]. PMID- 21028694 TI - [Not Available]. PMID- 21028695 TI - Tuberculin studies; comparative potency determinations of tuberculin fractions obtained as a result of ultrafiltration and trichloracetic acid precipitation. PMID- 21028696 TI - Injury as a cause of mastitis. PMID- 21028697 TI - Method for the recovery of Nematodirus adults, eggs and larvae for experimental purposes. PMID- 21028698 TI - Production of dehydrated goatmeat for the defence forces. PMID- 21028699 TI - Management and improvement of grasslands. PMID- 21028700 TI - Pig disease in the Army development farms. PMID- 21028701 TI - Trichomoniasis in young pigeons. PMID- 21028702 TI - A case of congenital contracted tendons in a bull calf. PMID- 21028703 TI - Penicillin therapy in canine practice. PMID- 21028704 TI - A case of Hepatozoon canis. PMID- 21028705 TI - A case of abnormal foetal development. PMID- 21028706 TI - Clinical legal communications; the dyed greyhound case. PMID- 21028707 TI - Fits. PMID- 21028708 TI - Treatment of papiloma in dogs. PMID- 21028709 TI - A caesarean section in a cow and after. PMID- 21028710 TI - Sporadic diseases of sheep. PMID- 21028711 TI - Blood parasites of turkeys. PMID- 21028712 TI - Artifically induced case of pyelonephritis in a bovine. PMID- 21028714 TI - A useful method of appraising the adequacy of swine rations. PMID- 21028713 TI - Euthanasia in small animals. PMID- 21028715 TI - Pullorum disease of turkeys. PMID- 21028716 TI - The veterinarian's place in artificial insemination. PMID- 21028717 TI - The trend in fly control. PMID- 21028718 TI - [Not Available]. PMID- 21028719 TI - [Not Available]. PMID- 21028720 TI - [Not Available]. PMID- 21028721 TI - [Not Available]. PMID- 21028722 TI - [Not Available]. PMID- 21028723 TI - [Not Available]. PMID- 21028725 TI - [Not Available]. PMID- 21028724 TI - [Not Available]. PMID- 21028726 TI - [Not Available]. PMID- 21028727 TI - [Not Available]. PMID- 21028728 TI - [Not Available]. PMID- 21028729 TI - [Not Available]. PMID- 21028730 TI - The future of surgery on the horse. PMID- 21028731 TI - Parasitic dermatitis in a horse. PMID- 21028732 TI - Lightning stroke. PMID- 21028733 TI - Report of Special Committee on Brucellosis of Cattle. PMID- 21028734 TI - Transfusions. PMID- 21028735 TI - Radiography of intestinal foreign bodies; report of two cases. PMID- 21028736 TI - UNRRA livestock importation problems in Greece. PMID- 21028737 TI - Diagnosis of tuberculosis. PMID- 21028738 TI - Clinical observation of 1080 poisoning. PMID- 21028739 TI - Uses and limitations of DDT. PMID- 21028740 TI - Histamine theory and treatment of laminitis. PMID- 21028741 TI - Contagious ovine pneumonia caused by a filterable virus. PMID- 21028742 TI - A practitioner's view of brucellosis in dairy cattle. PMID- 21028744 TI - X disease. PMID- 21028743 TI - Delivery of bovine monster; schistocormus reflexus. PMID- 21028745 TI - Double inguinal hernia in a bitch. PMID- 21028746 TI - A method of treating dislocated hip joints. PMID- 21028747 TI - Treatment of the pneumonia-enteritis complex in swine. PMID- 21028748 TI - Intracisternal injection of potassium phosphate in the dog. PMID- 21028758 TI - Effect of pressure on tautomers' equilibrium in supercooled glibenclamide drug: analysis of fragility behavior. AB - In this work, we investigated the relaxation dynamics of supercooled and glassy glibenclamide drug in conditions of high compression using broadband dielectric spectroscopy. Glibenclamide, an oral antidiabetic drug, belongs to the group of organic compounds which reveal amide-imidic acid tautomerism. Our studies reveal that application of pressure does not change the shape of dielectric loss spectrum of this pharmaceutical, whereas it probably influences the tautomers' concentration in the examined sample. Because every tautomer may influence the unique physical properties like the glass transition temperature, we have also focused on the analysis of pressure dependence of fragility, m(P)(P). In contradiction to the others active pharmaceutical ingredients (API) like verapamil hydrochloride, indomethacin or ibuprofen, in the case of glibenclamide drug slightly increasing trend of fragility was observed. On the other hand, pressure measurements confirmed the validity of suggestions concerning the origins of two secondary relaxations in glibenclamide presented in our previous paper (Wojnarowska et al. Mol. Pharmaceutics 2010, 7, 1692-1707). It is worth noting that until now the system which reveals tautomerism has never been analyzed in condition of high compression. PMID- 21028759 TI - Quantitative testing of robustness on superomniphobic surfaces by drop impact. AB - The quality of a liquid-repellent surface is quantified by both the apparent contact angle theta(0) that a sessile drop adopts on it and the value of the liquid pressure threshold the surface can withstand without being impaled by the liquid, hence maintaining a low-friction condition. We designed surfaces covered with nanowires obtained by the vapor-liquid-solid (VLS) growth technique that are able to repel most of the existing nonpolar liquids including those with very low surface tension as well as many polar liquids with moderate to high surface tension. These superomniphobic surfaces exhibit apparent contact angles ranging from 125 to 160 degrees depending on the liquid. We tested the robustness of the surfaces against impalement by carrying out drop impact experiments. Our results show how this robustness depends on Young's contact angle theta(0) related to the surface tension of the liquid and that the orientational growth of nanowires is a favorable factor for robustness. PMID- 21028760 TI - Investigation of the local structure in sub and supercritical ammonia using the nearest neighbor approach: a molecular dynamics analysis. AB - Molecular dynamics simulations of ammonia were performed in the (N,P,T) ensemble along the isobar 135 bar and in the temperature range between 250 and 500 K that encompasses the sub and supercritical states of ammonia. Six simple interaction potential models (Lennard-Jones pair potential between the atomic sites, plus a Coulomb interaction between atomic partial charges) of ammonia reported in the literature were analyzed. Liquid-gas coexistence curve, critical temperature, and structural data (radial distribution functions) have been calculated for all models and compared with the corresponding experimental data. After choosing the appropriate potential model, we have investigated the local structure by analyzing the nearest neighbor radial, mutual orientation, and interaction energy distributions. The change in the local structure was traced back to the change of the nonlinear behavior (which is more pronounced at low temperatures) of the average distance between a reference ammonia molecule and its subsequent nearest neighbor. Our results suggest to use the position of the maximum in the fluctuation of the average distance to define the border of the first solvation shell (particularly at high temperature when the minimum of the radial distribution is not well-defined). Indeed, the effect of the temperature on the position of this maximum shows clearly that the spatial extent of the solvation shell increases with a concomitant decrease of the involved number of ammonia molecules. Furthermore, our results show that the signature of the hydrogen bonding is mainly observed for temperature below 300 K. This signature is quantified by a short distance contribution to the closest radial nearest neighbor distribution, by a strong mutual orientation (defined by the angles between the axis joining the nitrogen atoms and the molecular axes) and by a strong attractive character of the total interaction energy. PMID- 21028761 TI - Influence of the lipid phase state and electrostatic surface potential on the conformations of a peripherally bound membrane protein. AB - Avian liver bile acid-binding protein (L-BABP) binds peripherically to anionic lipid membranes. We previously showed that in the absence of added salt the binding to 1,2-dimyristoyl-sn-glycero-3-phosphoglycerol (DMPG) occurs with changes in the secondary structure, the extent of which depends on the phase state of the lipid. In the present work, we used Fourier transform infrared spectroscopy to study the conformations of L-BABP bound to lipids with phosphoglycerol and phosphatidic acid polar head groups and with different transition temperatures in an aqueous medium with high ionic strength (0.1 M NaCl). When L-BABP was bound to the lipids with saturated acyl chains, DMPG, 1,2 dipalmitoyl-sn-glycero-3-phosphoglycerol (DPPG), 1,2-dimyristoyl-sn-glycero-3 phosphate (DMPA), and 1,2-dilauroyl-sn-glycero-3-phosphate (DLPA), the conformation shifted from a native-like secondary structure to an unfolded state at the temperature of lipid chain melting. The protein was in the native-like conformation when it was bound to the unsaturated 1-palmitoyl-2-oleoyl-sn-glycero 3-phosphoglycerol (POPG) in the liquid-crystalline phase. We also measured the electrokinetic surface potential of POPG and DMPG vesicles in the gel and in the liquid-crystalline phase and the protein binding constant to these lipid membranes. We found a correlation indicating that protein unfolding in the interface was due to the increase in the electrostatic surface potential that occurs in the lipid phase transition. PMID- 21028762 TI - Enhanced two-photon emission in coupled metal nanoparticles induced by conjugated polymers. AB - Interactions between noble metal (Ag and Au) nanoparticles and conjugated polymers as well as their one- and two-photon emission have been investigated. Ag and Au nanoparticles exhibited extraordinary quenching effects on the fluorescence of cationic poly(fluorinephenylene). The quenching efficiency by 37 nm Ag nanoparticles is ~19 times more efficient than that by 13-nm Au nanoparticles, and 9-10 orders of magnitude more efficient than typical small molecule dye-quencher pairs. On the other hand, the cationic conjugated polymers induce the aggregate formation and plasmonic coupling of the metal nanoparticles, as evidenced by transmission electron microscopy images and appearance of a new longitudinal plasmon band in the near-infrared region. The two-photon emissions of Ag and Au nanoparticles were found to be significantly enhanced upon addition of conjugated polymers, by a factor of 51-times and 9-times compared to the isolated nanoparticles for Ag and Au, respectively. These studies could be further extended to the applications of two-photon imaging and sensing of the analytes that can induce formation of metal nanoparticle aggregates, which have many advantages over the conventional one-photon counterparts. PMID- 21028763 TI - Kinetic and thermodynamic aspects of enzyme control and regulation. AB - This paper develops concepts for assessing and quantifying the regulation of the rate of an enzyme-catalyzed reaction. We show how generic reversible rate equations can be recast in two ways, one making the distance from equilibrium explicit, thereby allowing the distinction between kinetic and thermodynamic control of reaction rate, as well as near-equilibrium and far-from-equilibrium reactions. Recasting in the second form separates mass action from rate capacity and quantifies the degree to which intrinsic mass action contributes to reaction rate and how regulation of an enzyme-catalyzed reaction either enhances or counteracts this mass-action behavior. The contribution of enzyme binding to regulation is analyzed in detail for a number of enzyme-kinetic rate laws, including cooperative reactions. PMID- 21028764 TI - FRET efficiency distributions of multistate single molecules. AB - A simple analytic theory is developed to describe FRET efficiency histograms constructed from a photon trajectory generated by a molecule with multiple conformational states. The histograms are approximated by a sum of Gaussians with the parameters explicitly determined by the FRET efficiencies of the states and the rates of the transitions between the states. The theory, which has been tested against exact histograms for two conformational states and simulated data for three and four conformational states, accurately describes how the peaks in the histograms collapse as the bin time or the transition rates increase. PMID- 21028766 TI - Evidence for the formation of an interstellar species, HCS+, during the ionic fragmentation of methyl thiofluoroformate, FC(O)SCH3, in the 100-1000 eV region. AB - Total ion yield spectra and photoinduced fragmentations following S 2p, C 1s, O 1s, and F 1s inner shell excitations of methyl thiofluoroformate, FC(O)SCH(3), have been studied in the gaseous phase by using synchrotron radiation and multicoincidence techniques, which include photoelectron-photoion coincidence (PEPICO) and photoelectron-photoion-photoion coincidence (PEPIPICO) time-of flight mass spectrometry. Fragmentation patterns deduced from PEPICO spectra at the various excitation energies show a moderate site-specific fragmentation. The dissociation dynamic for the main ion-pair production has been discussed. Two-, three-, and four-body dissociation channels have been observed in the PEPIPICO spectra, and the dissociation mechanisms were proposed. The high stability of the interstellar HCS(+) ion can be observed over the whole range of photon energies analyzed. PMID- 21028765 TI - Effect of oxygen plasma treatment on crystal growth mode at pentacene/Ni interface in organic thin-film transistors. AB - We report how treatment of nickel (Ni) with O(2) plasma affects the polarity of Ni surface, crystallinity of pentacene film on the Ni, and electrical properties of pentacene organic thin-film transistors (OTFTs) that use Ni as source-drain electrodes. The polar component of surface energy in Ni surface increased from 8.1 to 43.3 mJ/m(2) after O(2)-plasma treatment for 10 s. From X-ray photoelectron spectra and secondary electron emission spectra, we found that NiO(x) was formed on the O(2)-plasma-treated Ni surface and the work function of O(2)-plasma-treated Ni was 0.85 eV higher than that of untreated Ni. X-ray diffraction and atomic force microscopy measurements showed that pentacene molecules are well aligned as a thin-film and grains grow much larger on O(2) plasma-treated Ni than on untreated Ni. This change in the growth mode is attributed to the reduction of interaction energy between pentacene and Ni due to formation of oxide at the Ni/pentacene interface. Thus, O(2)-plasma treatment promoted the growth of well-ordered pentacene film and lowered both the hole injection barrier and the contact resistance between Ni and pentacene by forming NiO(x), enhancing the electrical property of bottom-contact OTFTs. PMID- 21028767 TI - Configuration changes of conducting channel network in Nafion membranes due to thermal annealing. AB - We have investigated changes of proton channel network in Nafion membranes annealed at elevated temperatures using current sensing atomic force microscopy aimed at understanding the aging process of the membranes. The results reveal that the changes of proton channel network undergo two steps: First, the configuration of the ionic domains on the membrane surface changes from cluster like to chain-like structure, accompanied by an increase of the proton conductivity of the membrane. As the annealing continues, the chain-like configuration for the proton channels persists but the conductance of the membranes decreases. The time constant of the conductivity decay decreases with the annealing temperature. The observed changes can be explained in terms of reorientation of proton channels near the membrane surface from perpendicular to parallel to the surface as the annealing temperature approaches the glass transition of the membranes. PMID- 21028768 TI - Receptacle model of salting-in by tetramethylammonium ions. AB - Water is a poor solvent for nonpolar solutes. Water containing ions is an even poorer solvent. According to standard terminology, the tendency of salts to precipitate oils from water is called salting-out. However, interestingly, some salt ions, such as tetramethylammonium (TMA), cause instead the salting-in of hydrophobic solutes. Even more puzzling, there is a systematic dependence on solute size. TMA causes the salting-out of small hydrophobes and the salting-in of larger nonpolar solutes. We study these effects using NPT Monte Carlo simulations of the Mercedes-Benz (MB) + dipole model of water, which was previously shown to account for hydrophobic effects and ion solubilities in water. The present model gives a structural interpretation for the thermodynamics of salting-in. The TMA structure allows deep penetration by a first shell of waters, the dipoles of which interact electrostatically with the ion. This first water shell sets up a second water shell that is shaped to act as a receptacle that binds the nonpolar solute. In this way, a nonpolar solute can actually bind more tightly to the TMA ion than to another hydrophobe, leading to the increased solubility and salting-in. Such structuring may also explain why molecular ions do not follow the same charge density series as atomic ions do. PMID- 21028769 TI - Isotropic non-Heisenberg behavior in M3(dpa)4Cl2 extended metal atom chains. AB - Isotropic deviations to the standard Heisenberg Hamiltonian have been extracted for a series of trinuclear extended metal atom chain complexes, namely, [Ni(3)(dpa)(4)Cl(2)], and the hypothetical [NiPdNi(dpa)(4)Cl(2)] and [Pd(3)(dpa)(4)Cl(2)], following a scheme recently proposed by Labeguerie and co workers (J. Chem. Phys 2008, 129, 154110) within the density functional theory framework. Energy calculations of broken symmetry monodeterminantal solutions of intermediate M(s,tot.) values can provide an estimate of the magnitude of the biquadratic exchange interaction (lambda) that accounts for these deviations in systems with S = 1 magnetic sites. With the B3LYP functional, we obtain lambda = 1.37, 13.8, and 498 cm(-1) for the three molecules, respectively, meaning that a simple Heisenberg Hamiltonian is enough for describing the magnetic behavior of the Ni(3) complex but definitely not for Pd(3). In the latter case, the origin of such extreme deviation arises from (i) an energetically affordable local non-Hund state (small intrasite exchange integral, K ~ 1960 cm(-1)) and (ii) a very effective overlap between Pd-4d orbitals and a large J. Furthermore, this procedure enables us to determine the relative weights of the two types of magnetic interactions, sigma- and delta-like, that contribute to the total magnetic exchange (J = J(sigma) + J(delta)). In all of the systems, J is governed by the sigma interaction by 95-98%. PMID- 21028770 TI - Observation of the crystallization and supersaturation of mixed component NaNO3 Na2SO4 droplets by FTIR-ATR and Raman spectroscopy. AB - We present here a study of the phase behavior of mixed component NaNO(3) Na(2)SO(4) (SNS) droplets with NaNO(3) to Na(2)SO(4) molar ratios of 1:1, 3:1, and 10:1, comparing observations with thermodynamic predictions. Measurements are made by Fourier transform infrared attenuated total reflection and micro-Raman spectroscopy for SNS droplets deposited on ZnSe and quartz substrates, respectively. The conventional deliquescence/efflorescence hysteresis in phase behavior is observed. On drying, heterogeneous crystallization leads to phase behavior that is consistent with bulk solution thermodynamics, with the formation of the mixed salt NaNO(3).Na(2)SO(4).H(2)O, Na(2)SO(4) (s), and NaNO(3) (s) all observed to form at relative humidities that coincide with predictions by the aerosol inorganics model. However, conditioning of the droplet at high relative humidity prior to drying is observed to lead to quantitative differences between the fractions of different salts formed. When substrate effects do not influence the crystallization process, supersaturated solutions are formed, and this leads to the observation of contact ion pairs. Such measurements of the phase behavior of mixed component droplets are important for testing the reliability of thermodynamic models. PMID- 21028771 TI - Adsorption of nonionic surfactants (CnEm) at the silica-water and cellulose-water interface. AB - The adsorption of nonionic surfactants to the silica-water and cellulose-water interfaces was studied using optical reflectometry (OR) and soft-contact atomic force microscopy imaging. The polyethylene oxide alkyl ethers C(14)E(6) and C(16)E(8) were shown to readily adsorb to both interfaces. The kinetics of the adsorption process as well as the equilibrium surface excess was determined using OR. In agreement with previous studies, the short headgroup surfactant C(14)E(6) adsorbed to a greater extent than the longer headgroup surfactant C(16)E(8) on silica. This trend was also observed for the cellulose-water interface. The structure of the adsorbed surfactant layer above the critical surface aggregation concentration (csac) was visualized using the soft contact imaging technique for both interfaces. On the silica surface, the layer structure for both surfactants mostly showed spherical aggregates, however, with some elongation into rods being more prevalent for C(14)E(6). Similar structures were observed on the cellulose surface, but imaging was more difficult due to the soft gel-like nature of the cellulose thin film in water. This suggests that these surfactants adsorb in a cooperative fashion above the critical micelle concentration (cmc) with a similar interaction between surfactant headgroup and surface for both silica and cellulose. No evidence was seen for the penetration of surfactant molecules into the cellulose surface or any solubilization of the interface. PMID- 21028772 TI - Synthesis of the landomycinone skeleton. AB - The synthesis of the highly functionalized tetracyclic skeleton of landomycinone (2), the aglycon of landomycins, was performed using two pivotal steps relying on metal-catalyzed reactions. They are (1) a [2 + 2 + 2] cycloaddition of alkynes promoted by Wilkinson's catalyst to build rings B and C concomitantly and (2) a ring-closing metathesis followed by aromatization to build ring D. PMID- 21028773 TI - Experimental and computed absolute redox potentials of polycyclic aromatic hydrocarbons are highly linearly correlated over a wide range of structures and potentials. AB - A more rigorous theoretical treatment of methods previously used to correlate computed energy values with experimental redox potentials, combined with the availability of well-developed computational solvation methods, results in a shift away from computing ionization potentials/electron affinities in favor of computing absolute reduction potentials. Seventy-nine literature redox potentials measured under comparable conditions from 51 alternant and nonalternant polycyclic aromatic hydrocarbons are linearly correlated with their absolute reduction potentials computed by density functional theory (B3LYP/6-31+G(d)) with SMD/IEF-PCM solvation. The resulting correlation is very strong (R(2) = 0.9981, MAD = 0.056 eV). When extrapolated to the x-intercept, the correlation results in an estimate of 5.17 +/- 0.01 eV for the absolute potential of the ferrocene ferrocenium redox couple in acetonitrile at 25 degrees C, indicating that this simple method can be used reliably for both calculating absolute redox potentials and for predicting relative redox potentials. When oxidation and reduction data are evaluated separately, the overall MAD value is improved by 50% to 0.028 eV, which improves relative potential predictions, but the computed values do not extrapolate to a reasonable estimate of the absolute potential of the ferrocene ferrocenium ion reference. PMID- 21028774 TI - Excited-state dynamics in fac-[Re(CO)3(Me4phen)(L)]+. AB - Excited-state dynamics in fac-[Re(CO)(3)(Me(4)phen)(cis-L)](+) (Me(4)phen = 3,4,7,8-tetramethyl-1,10-phenanthroline, L = 4-styrylpyridine (stpy) or 1,2-bis(4 pyridyl)ethylene (bpe)) were investigated by steady-state and time-resolved techniques. A complex equilibrium among three closely lying excited states, (3)IL(cis-L), (3)MLCT(Re->Me(4)phen), and (3)IL(Me(4)phen), has been established. Under UV irradiation, cis-to-trans isomerization of coordinated cis-L is observed with a quantum yield of 0.15 in acetonitrile solutions. This photoreaction competes with radiative decay from (3)MLCT(Re->Me(4)phen) and (3)IL(Me(4)phen) excited states, leading to a decrease in the emission quantum yield relative to the nonisomerizable complex fac-[Re(CO)(3)(Me(4)phen)(bpa)](+) (bpa = 1,2-bis(4 pyridyl)ethane). From temperature-dependent time-resolved emission measurements in solution and in poly(methyl methacrylate) (PMMA) films, energy barriers (DeltaE(a)) for interconversion between (3)MLCT(Re->Me(4)phen) and (3)IL(Me(4)phen) emitting states were determined. For L = cis-stpy, DeltaE(a) = 11 (920 cm(-1)) and 15 kJ mol(-1) (1254 cm(-1)) in 5:4 propionitrile/butyronitrile and PMMA, respectively. For L = cis-bpe, DeltaE(a) = 13 kJ mol(-1) (1087 cm(-1)) in 5:4 propionitrile/butyronitrile. These energy barriers are sufficient to decrease the rate constant for internal conversion from higher-lying (3)IL(Me(4)phen) state to (3)MLCT(Re->Me(4)phen), k(i) ? 10(6) s(-1). The decrease in rate allows for the observation of intraligand phosphorescence, even in fluid medium at room temperature. Our results provide additional insight into the role of energy gap and excited-state dynamics on the photochemical and photophysical properties of Re(I) polypyridyl complexes. PMID- 21028775 TI - A highly selective turn-on colorimetric, red fluorescent sensor for detecting mobile zinc in living cells. AB - We describe ZRL1, a turn-on colorimetric and red fluorescent zinc ion sensor. The Zn(2+)-promoted ring opening of the rhodamine spirolactam ring in ZRL1 evokes a 220-fold fluorescence turn-on response. In aqueous media, ZRL1 turn-on luminescence is highly selective for Zn(2+) ions, with no significant response to other competitive cations, including Na(+), K(+), Ca(2+), Mg(2+), Mn(2+), Fe(2+), Co(2+), Ni(2+), Cu(2+), Cd(2+), or Hg(2+). In addition to these characteristics, preliminary results indicate that ZRL1 can be delivered to living cells and can be used to monitor changes in intracellular Zn(2+) levels. PMID- 21028776 TI - Soft wall ion channel in continuum representation with application to modeling ion currents in alpha-hemolysin. AB - A soft repulsion (SR) model of short-range interactions between mobile ions and protein atoms is introduced in the framework of continuum representation of the protein and solvent. The Poisson-Nernst-Plank (PNP) theory of ion transport through biological channels is modified to incorporate this soft wall protein model. Two sets of SR parameters are introduced. The first is parametrized for all essential amino acid residues using all atom molecular dynamic simulations; the second is a truncated Lennard-Jones potential. We have further designed an energy-based algorithm for the determination of the ion accessible volume, which is appropriate for a particular system discretization. The effects of these models of short-range interactions were tested by computing current-voltage characteristics of the alpha-hemolysin channel. The introduced SR potentials significantly improve prediction of channel selectivity. In addition, we studied the effect of the choice of some space-dependent diffusion coefficient distributions on the predicted current-voltage properties. We conclude that the diffusion coefficient distributions largely affect total currents and have little effect on rectifications, selectivity, or reversal potential. The PNP-SR algorithm is implemented in a new efficient parallel Poisson, Poisson-Boltzmann, and PNP equation solver, also incorporated in a graphical molecular modeling package HARLEM. PMID- 21028777 TI - Complex alloys containing double-Mackay clusters and (Sb(1-delta)Zn(delta))(24) snub cubes filled with highly disordered zinc aggregates: synthesis, structures, and physical properties of ruthenium zinc antimonides. AB - A series of cluster-based ruthenium zinc antimonides with a large unit cell were obtained. Their structures were solved by the single crystal X-ray diffraction methods. They crystallize in the cubic space group of Fm3c (No. 226) with cell dimensions of 25.098(3), 24.355(3), 24.307(3), and 24.376(3) A for Ru(26)Sb(24)Zn(67) (CA), Ru(13)Sb(12)Zn(83.4) (CB), Ru(13)Sb(6.29)Zn(91.56) (CC), and Ru(13)Sb(17.1)Zn(74.8) (CD), respectively. By all indications, compounds CA and CB are two phases showing pronounced distinctions regarding compositions, lattice parameters, thermal and transport properties, but they are not members of an extended solid solution. Compounds CB, CC, and CD are three members of a same solid solution. Topologically, these four compounds contain face-centered cubic packing of double-Mackay type clusters and (Sb(1-delta)Zn(delta))(24) snub cubes filled with highly disordered zinc aggregates, with or without glue atoms between them. Both phases CA and CB are diamagnetic. There is a difference of ~170 K between their thermally stable temperatures. CA exhibits rather low thermal conductivity with the value of ~0.9 W m(-1) K(-1) at room temperature, which is about one-third that of CB. The electrical resistivity of CB is almost temperature independent. The Seebeck coefficient of CB is small and negative, while that of CA exhibits a complicated temperature dependence and undergoes a transition from p- to n-type conduction around room temperature. PMID- 21028778 TI - Energetics of the lighter chalcogen analogues of carboxylic acid esters. AB - In the current paper we present the results of our quantum chemical (G2, G2(MP2), and G3) study of the structure and energetics of carboxylic acids and their chalcogen analogues. In the particular, calculations and accompanying natural bond orbital (NBO) and atoms in molecules (AIM) analyses were performed on all species with the generic formula RC(?X)YR' (X, Y = O, S, Se and R = R' = CH(3)). Energies, enthalpies, and free energies of formation, resonance energies, interchalcogen methyl transfer energies and their energies of activation, and heavy atom bond lengths and angles are all discussed. A comparison of the calculated results with the sparse experimentally available data shows good agreement. Trends are also presented. PMID- 21028780 TI - Nanopolaritons: vacuum Rabi splitting with a single quantum dot in the center of a dimer nanoantenna. AB - We demonstrate with accurate scattering calculations that a system constituted by a single quantum emitter (a semiconductor quantum dot) placed in the gap between two metallic nanoparticles can display the vacuum Rabi splitting. The largest dimension of the investigated system is only 36 nm. This nonperturbative regime is highly desirable for many possible applications in quantum information processing or schemes for controlling individual photons. Along this road, it will be possible to implement scalable photonic quantum computation without renouncing to the nanometric size of the classical logic gates of the present most compact electronic technology. PMID- 21028779 TI - Biological nanofactories target and activate epithelial cell surfaces for modulating bacterial quorum sensing and interspecies signaling. AB - In order to control the behavior of bacteria present at the surface of human epithelial cells, we have created a biological "nanofactory" construct that "coats" the epithelial cells and "activates" the surface to produce the bacterial quorum sensing signaling molecule, autoinducer-2 (AI-2). Specifically, we demonstrate directed modulation of signaling among Escherichia coli cells grown over the surface of human epithelial (Caco-2) cells through site-directed attachment of biological nanofactories. These "factories" comprise a fusion protein expressed and purified from E. coli containing two AI-2 bacterial synthases (Pfs and LuxS), a protein G IgG binding domain, and affinity ligands for purification. The final factory is fabricated ex vivo by incubating with an anti-CD26 antibody that binds the fusion protein and specifically targets the CD26 dipeptidyl peptidase found on the outer surface of Caco-2 cells. This is the first report of the intentional "in vitro" synthesis of bacterial autoinducers at the surface of epithelial cells for the redirection of quorum sensing behaviors of bacteria. We envision tools such as this will be useful for interrogating, interpreting, and disrupting signaling events associated with the microbiome localized in human intestine and other environments. PMID- 21028781 TI - Self-assembled 3D heterometallic Cu(II)/Fe(II) coordination polymers with octahedral net skeletons: structural features, molecular magnetism, thermal and oxidation catalytic properties. AB - The new three-dimensional (3D) heterometallic Cu(II)/Fe(II) coordination polymers [Cu(6)(H(2)tea)(6)Fe(CN)(6)](n)(NO(3))(2n).6nH(2)O (1) and [Cu(6)(Hmdea)(6)Fe(CN)(6)](n)(NO(3))(2n).7nH(2)O (2) have been easily generated by aqueous-medium self-assembly reactions of copper(II) nitrate with triethanolamine or N-methyldiethanolamine (H(3)tea or H(2)mdea, respectively), in the presence of potassium ferricyanide and sodium hydroxide. They have been isolated as air-stable crystalline solids and fully characterized including by single-crystal X-ray diffraction analyses. The latter reveal the formation of 3D metal-organic frameworks that are constructed from the [Cu(2)(MU-H(2)tea)(2)](2+) or [Cu(2)(MU-Hmdea)(2)](2+) nodes and the octahedral [Fe(CN)(6)](4-) linkers, featuring regular (1) or distorted (2) octahedral net skeletons. Upon dehydration, both compounds show reversible escape and binding processes toward water or methanol molecules. Magnetic susceptibility measurements of 1 and 2 reveal strong antiferromagnetic [J = -199(1) cm(-1)] or strong ferromagnetic [J = +153(1) cm(-1)] couplings between the copper(II) ions through the MU-O-alkoxo atoms in 1 or 2, respectively. The differences in magnetic behavior are explained in terms of the dependence of the magnetic coupling constant on the Cu-O-Cu bridging angle. Compounds 1 and 2 also act as efficient catalyst precursors for the mild oxidation of cyclohexane by aqueous hydrogen peroxide to cyclohexanol and cyclohexanone (homogeneous catalytic system), leading to maximum total yields (based on cyclohexane) and turnover numbers (TONs) up to about 22% and 470, respectively. PMID- 21028782 TI - Controlled assembly of ruthenium complexes through ortho-carborane dithiolate and polysulfide ligands. AB - Treatment of ortho-carborane, n-butyl lithium, sulfur, and [(p-cymene)RuCl(2)](2) in varying ratio led to four new compounds (p-cymene)Ru[S(3)(C(2)B(10)H(10))(2)] (3), [(p-cymene)Ru(2)(MU(2)-S(2)C(2)B(10)H(9))(MU(3)-S(2)C(2)B(10)H(10))](2) (4), [(p-cymene)Ru](2)Ru(MU(2)-eta(2):eta(2)-S(2)) (MU(2)-eta(2):eta(1)-S(2)Cl)(MU(2) S(2)C(2)B(10)H(10))(2) (5), and [(p-cymene)Ru](2)Ru(MU(2)-eta(1):eta(1) S(2))(MU(3)-eta(2):eta(2)-S(4)) (MU(2)-S(2)C(2)B(10)H(10))(2) (6), respectively. In 3, the ruthenium atom is coordinated by three S atoms from a in situ generated tridentate [S(3)(C(2)B(10)H(10))(2)](2-) ligand. 4 consists of two identical dinuclear (p-cymene)Ru(2)(MU(2)-S(2)C(2)B(10)H(9))(MU(3)-S(2)C(2)B(10)H(10)) subunits which connect to each other via the Ru-Ru bond and two bridging o carborane-1,2-dithiolate ligands. In 4, a Ru-B bond is present. 5 contains a Ru(3)(MU(2)-S)(2)(MU(2)-S(2))(MU(2)-S(2)Cl) core, and the central ruthenium atom is coordinated by seven S atoms in a distorted pentagonal bipyramidal geometry. In 5, a S-Cl bond is generated. 6 has a novel Ru(3)(MU(2)-S)(2)(MU(2)-S(2))(MU(3) S(4)) core, and the three ruthenium atoms are connected through the two terminal sulfur atoms of the S-S-S-S chain in a MU(3) binding fashion. All the four complexes have been characterized by elemental analysis, mass, NMR, and X-ray crystallography. PMID- 21028784 TI - Sol-gel-derived epitaxial nanocomposite thin films with large sharp magnetoelectric effect. AB - Nanostructures of multiferroic materials have drawn increasing interest due to the enhanced magnetoelectric coupling and potential for next-generation multifunctional devices. Most of these structures are typically prepared by thin film evaporation approaches. Herein, however, we report a novel sol-gel-based process to synthesize epitaxial BaTiO(3)-CoFe(2)O(4) nanocomposite thin films via phase separation and enhanced heterogeneous nucleation. The magnetoelectric coupling effect is investigated by examining the temperature-dependent magnetization of the composite film, which manifests as a sharp and significant drop (>50%) of the magnetization at the vicinity of a BaTiO(3) ferroelectric phase transition. We propose that the phase transition in BaTiO(3) is mediated by the tensile strain due to intimate coupling to CoFe(2)O(4) phase, which has rarely been reported before. The significant coupling effect is attributed to the small substrate clamping, and the large areal distribution of intimate heteroepitaxial interfaces between the three-dimensionally distributed ferroelectric and magnetic nanostructured phases. PMID- 21028783 TI - Gold nanoparticles promote osteogenic differentiation of mesenchymal stem cells through p38 MAPK pathway. AB - Understanding the interaction mechanisms between nanomaterials and biological cells is important for the control and manipulation of these interactions for biomedical applications. In this study, we investigated the cellular effects of gold nanoparticles (AuNPs) on the differentiation of mesenchymal stem cells (MSCs) and the associated molecular mechanisms. The results showed that AuNPs promoted the differentiation of MSCs toward osteoblast cells over adipocyte cells by inducing an enhanced osteogenic transcriptional profile and an attenuated adipogenic transcriptional profile. AuNPs exerted the effects by interacting with the cell membrane and binding with proteins in the cytoplasm, causing mechanical stress on the MSCs to activate p38 mitogen-activated protein kinase pathway (MAPK) signaling pathway, which regulates the expression of relevant genes to induce osteogenic differentiation and inhibit adipogenic differentiation. PMID- 21028785 TI - Pillaring chemically exfoliated graphene oxide with carbon nanotubes for photocatalytic degradation of dyes under visible light irradiation. AB - Graphene oxide (GO) and reduced graphene oxide (RGO) platelets were pillared with carbon nanotubes (CNTs) by using the chemical vapor deposition (CVD) method with acetonitrile as the carbon source and nickel nanoparticles as the catalyst, aimed to prepare graphene-based materials with a high surface area and a good electrical conductivity. Characterization data showed that the composite materials with RGO layers pillared by CNTs formed a robust three-dimensional (3D) porous structure of specific surfaces as high as 352 m(2)/g. The amount and length of the CNT pillars connecting the RGO layers were controlled by changing the amount of the nickel metal catalyst and the time of CVD. The CNT-pillared RGO composite materials exhibited an excellent visible light photocatalytic performance in degrading dye Rhodamine B because of the unique porous structure and the exceptional electron transfer property of graphene. Such CNT-RGO composites represent a new family of innovative carbon materials for visible light-activated photocatalysis. PMID- 21028786 TI - Chiral cyclobutane synthesis by exploiting a heteroatom-directed conjugate addition. AB - The syntheses of both enantiomers of cyclobutanes B and ent-B are achieved through heteroatom-directed conjugate addition (HADCA) of nucleophiles to the epoxyvinylsulfone-substituted carbohydrates A and ent-A, which provided carbanions that intramolecularly attacked the epoxide with concomitant formation of the cyclobutane ring. PMID- 21028787 TI - Efficient approach to 3,3-bissilyl carbonyl and enol derivatives via retro-[1,4] brook rearrangement of 3-silyl allyloxysilanes. AB - A facile and highly stereoselective retro-[1,4] Brook rearrangement of 3-silyl allyloxysilanes has been discovered. While basic hydrolysis of the formed (Z)-3,3 bissilyl lithium enolates provides 3,3-bissilyl carbonyl compounds efficiently, trapping the species with various electrophiles including alkyl halides leads to the exclusive O-substituted (Z)-3,3-bissilyl enol derivatives that can undergo a Sakurai reaction with aldehyde to produce the synthetically useful 1,2-diol diastereoselectively. PMID- 21028788 TI - Synthesis of a functionalized 7,6-bicyclic spiroimine ring fragment of the spirolides. AB - The asymmetric synthesis of a functionalized 7,6-spiroimine related to the spirolides is described. Intermolecular Diels-Alder cycloaddition of a chiral trisubstituted dienophile and Danishefsky's diene enabled simultaneous installation of the C7 and C29 stereocenters. Further transformations and late stage aza-Wittig cyclization afforded the spiroimine in good yield. During this study, an unprecedented 14-membered dialdimine was also obtained. PMID- 21028789 TI - Room-temperature metal-free electrophilic 5-endo-selective iodocarbocyclization of 1,5-enynes. AB - A highly efficient NIS-promoted iodocarbocyclization reaction of various functionalized 1,5-enynes is described via a 5-endo diastereoselective process. The cyclizations are conducted in the presence of 1.2 equiv of N-iodosuccinimide in dichloromethane at room temperature. The reaction conditions are compatible with several functional groups and lead to original iodo-functionalized carbocycles in good to excellent yields. PMID- 21028790 TI - Reaction of singlet oxygen with thioanisole in ionic liquid-acetonitrile binary mixtures. AB - A study of the reaction of thioanisole with singlet oxygen in different ionic liquid-acetonitrile binary mixtures has shown that ILs are able to accelerate the thioanisole sulfoxidation when used as additives. With imidazolium ILs, the maximum efficiency is reached at x(IL) ~ 0.1-0.2, whereas for the pyrrolidinium IL a plateau is reached. These results are discussed in terms of the ILs' tendency to form ionic aggregates and of differences in sulfoxidation reaction mechanism. PMID- 21028791 TI - Synthesis of the C(18)-C(34) fragment of amphidinolide C and the C(18)-C(29) fragment of amphidinolide F. AB - A convergent synthesis of the C(18)-C(34) fragment of amphidinolide C and the C(18)-C(29) fragment of amphidinolide F is reported. The approach involves the synthesis of the common intermediate tetrahydrofuranyl-beta-ketophosphonate via cross metathesis, Pd(0)-catalyzed cyclization, and hydroboration-oxidation. The beta-ketophosphonate was coupled to three side chain aldehydes using a Horner Wadsworth-Emmons (HWE) olefination reaction to give dienones, which were reduced with l-selectride to give the fragments of amphidinolide C and F. PMID- 21028792 TI - Importance of controlling nanotube density for highly sensitive and reliable biosensors functional in physiological conditions. AB - Biosensors utilizing carbon nanotube field-effect transistors have a tremendous potential to serve as the basis for the next generation of diagnostic systems. While nanotubes have been employed in the fabrication of multiple sensors, little attention has previously been paid to how the nanotube density affects the biosensor performance. We conducted a systematic study of the effect of density on the performance of nanotube biosensors and discovered that this parameter is crucial to achieving consistently high performance. We found that devices with lower density offer higher sensitivity in terms of both detection limit and magnitude of response. The low density nanotube devices resulted in a detection limit of 1 pM in an electrolyte buffer containing high levels of electrolytes (ionic concentration ~140 mM, matching the ionic strength of serum and plasma). Further investigation suggested that the enhanced sensitivity arises from the semiconductor-like behavior-strong gate dependence and lower capacitance-of the nanotube network at low density. Finally, we used the density-optimized nanotube biosensors to detect the nucleocapsid (N) protein of the SARS virus and demonstrated improved detection limits under physiological conditions. Our results show that it is critical to carefully tune the nanotube density in order to fabricate sensitive and reliable devices. PMID- 21028793 TI - Reduced graphene oxide and porphyrin. An interactive affair in 2-D. AB - Photoexcited cationic 5,10,15,20-tetrakis(1-methyl-4-pyridinio)porphyrin tetra(p toluenesulfonate) (TMPyP) undergoes charge-transfer interaction with chemically reduced graphene oxide (RGO). Formation of the ground-state TMPyP-RGO complex in solution is marked by the red-shift of the porphyrin absorption band. This complexation was analyzed by Benesi-Hildebrand plot. Porphyrin fluorescence lifetime reduced from 5 to 1 ns upon complexation with RGO, indicating excited state interaction between singlet excited porphyrin and RGO. Femtosecond transient absorption measurements carried out with TMPyP adsorbed on RGO film revealed fast decay of the singlet excited state, followed by the formation of a longer-living product with an absorption maximum around 515 nm indicating the formation of a porphyrin radical cation. The ability of TMPyP-RGO to undergo photoinduced charge separation was further confirmed from the photoelectrochemical measurements. TMPyP-RGO coated conducting glass electrodes are capable of generating photocurrent under visible excitation. These results are indicative of the electron transfer between photoexcited porphyrin and RGO. The role of graphene in accepting and shuttling electrons in light-harvesting assemblies is discussed. PMID- 21028795 TI - Advances in proximal fluid proteomics for disease biomarker discovery. AB - Although serum/plasma has been the preferred source for identification of disease biomarkers, these efforts have been met with little success, in large part due the relatively small number of highly abundant proteins that render the reliable detection of low abundant disease-related proteins challenging due to the expansive dynamic range of concentration of proteins in this sample. Proximal fluid, the fluid derived from the extracellular milieu of tissues, contains a large repertoire of shed and secreted proteins that are likely to be present at higher concentrations relative to plasma/serum. It is hypothesized that many, if not all, proximal fluid proteins exchange with peripheral circulation, which has provided significant motivation for utilizing proximal fluids as a primary sample source for protein biomarker discovery. The present review highlights recent advances in proximal fluid proteomics, including the various protocols utilized to harvest proximal fluids along with detailing the results from mass spectrometry- and antibody-based analyses. PMID- 21028794 TI - Development of macroporous poly(ethylene glycol) hydrogel arrays within microfluidic channels. AB - The mass transport of solutes through hydrogels is an important design consideration in materials used for tissue engineering, drug delivery, and protein arrays used to quantify protein concentration and activity. We investigated the use of poly(ethylene glycol) (PEG) as a porogen to enhance diffusion of macromolecules into the interior of polyacrylamide and PEG hydrogel posts photopatterned within microfluidic channels. The diffusion of GST-GFP and dextran-FITC into hydrogels was monitored and effective diffusion coefficients were determined by fitting to the Fickian diffusion equations. PEG-diacrylate (M(r) 700) with porogen formed a macroporous structure and permitted significant penetration of 250 kDa dextran. Proteins copolymerized in these macroporous hydrogels retained activity and were more accessible to antibody binding than proteins copolymerized in nonporous gels. These results suggest that hydrogel macroporosity can be tuned to regulate macromolecular transport in applications such as tissue engineering and protein arrays. PMID- 21028796 TI - Polymer multilayers with pH-triggered release of antibacterial agents. AB - We report on the layer-by-layer design principles of poly(methacrylic acid) (PMAA) ultrathin hydrogel coatings that release antimicrobial agents (AmAs) in response to pH variations. The studied AmAs include gentamicin and an antibacterial cationic peptide L5. Adipic acid dihydrazide (AADH) is a cross linker which, relative to ethylenediamine (EDA), increases the hydrogel hydrophobicity and introduces centers for hydrogen bonding to AmAs. AmA retention in AADH-cross-linked hydrogels in high-salt solutions was enhanced while AmA release at low pH was suppressed. L5 retains its antibacterial activity toward planktonic Staphylococcus epidermidis after release from PMAA hydrogels in response to pH decreases in the surrounding medium due to bacterial growth. Staphylococcus epidermidis adhesion and colonization was almost completely inhibited by L5 loading of hydrogels. The AmA-releasing and AmA-retaining properties of these hydrogel coatings provide new opportunities to study the fundamental mechanisms of AmA-coating-bacteria interactions and develop a new class of clinically relevant antibacterial coatings for medical devices. PMID- 21028797 TI - In situ gellable oxidized citrus pectin for localized delivery of anticancer drugs and prevention of homotypic cancer cell aggregation. AB - The aim of this study was to develop in situ gellable hydrogels composed of periodate oxidized citrus pectin (OP) for localized anticancer drug delivery and evaluate the potential of OP to inhibit cancer metastasis. Doxorubicin (Dox) was coupled to OP by imine bonds. Adipic dihydrazide (ADH) was used for cross-linking of the Dox-OP conjugates. The Dox-OP conjugate solution gelled within 2 min after addition of ADH. The release rate of Dox from the hydrogels was controllable by an additive amount of ADH. The released Dox retained anticancer activity. OP was shown to have a potency to prevent homotypic cancer cell aggregation compared to unmodified citrus pectin, strongly suggesting that OP released from hydrogels in vivo will inhibit cancer metastasis. These results indicate that OP hydrogels have the potential to prevent progression of primary cancer by the released Dox and generation of metastatic cancer by the released OP. PMID- 21028798 TI - Synthesis and characterization of amphiphilic glycidol-chitosan-deoxycholic acid nanoparticles as a drug carrier for doxorubicin. AB - Novel amphiphilic chitosan derivatives (glycidol-chitosan-deoxycholic acid, G-CS DCA) were synthesized by grafting hydrophobic moieties, deoxycholic acid (DCA), and hydrophilic moieties, glycidol, with the purpose of preparing carriers for poorly soluble drugs. Based on self-assembly, G-CS-DCA can form nanoparticles with size ranging from 160 to 210 nm, and G-CS-DCA nanoparticles maintained stable structure for about 3 months when stored in PBS (pH 7.4) at room temperature. The critical aggregation concentration decreased from 0.043 mg/mL to 0.013 mg/mL with the increase of degree of substitution (DS) of DCA. Doxorubicin (DOX) could be easily encapsulated into G-CS-DCA nanoparticles and keep a sustained release manner without burst release when exposed to PBS (pH 7.4) at 37 degrees C. Antitumor efficacy results showed that DOX-G-CS-DCA have significant antitumor activity when MCF-7 cells were incubated with different concentration of DOX-G-CS-DCA nanoparticles. The fluorescence imaging results indicated DOX-G CS-DCA nanoparticles could easily be uptaken by MCF-7 cells. These results suggested that G-CS-DCA nanoparticles may be a promising carrier for DOX delivery in cancer therapy. PMID- 21028799 TI - Electrochemical deposition and surface-initiated RAFT polymerization: protein and cell-resistant PPEGMEMA polymer brushes. AB - This paper introduces a novel and versatile method of grafting protein and cell resistant poly(poly ethylene glycol methyl ether methacrylate) (PPEGMEMA) brushes on conducting Au surface. The process started with the electrochemical deposition and full characterization of an electro-active chain transfer agent (CTA) on the Au surface. The electrochemical behavior of the CTA was investigated by cyclic voltammetry (CV) while the deposition and stability of the CTA on the surface were confirmed by ellipsometry, contact angle, and X-ray photoelectron spectroscopy (XPS). The capability of the electrodeposited CTA to mediate surface initiated reversible addition-fragmentation chain transfer (SI-RAFT) polymerization on both the polymethyl methacrylate (PMMA; model polymer) and PPEGMEMA brushes was demonstrated by the increase in thicknesses of the films after polymerization. Contact angles also decreased with the incorporation of the more hydrophilic brushes. Significant changes in the morphologies of the films before and after polymerization were also observed with atomic force microscopy (AFM) analyses. Furthermore, XPS results showed an increase in the O 1s peak intensity relative to C 1s after polymerizations, which confirmed the grafting of polyethyleneglycol (PEG) bearing brushes. The ability of the PPEGMEMA-modified Au surface to resist nonspecific adhesion of proteins and cells was monitored and confirmed by XPS, ellipsometry, contact angle, AFM, and fluorescence imaging. The new method presented has potential application as robust protein and cell resistant coatings for electrically conducting electrodes and biomedical devices. PMID- 21028800 TI - Predicting acidification recovery at the Hubbard Brook Experimental Forest, New Hampshire: evaluation of four models. AB - The performance and prediction uncertainty (owing to parameter and structural uncertainties) of four dynamic watershed acidification models (MAGIC, PnET-BGC, SAFE, and VSD) were assessed by systematically applying them to data from the Hubbard Brook Experimental Forest (HBEF), New Hampshire, where long-term records of precipitation and stream chemistry were available. In order to facilitate systematic evaluation, Monte Carlo simulation was used to randomly generate common model input data sets (n = 10,000) from parameter distributions; input data were subsequently translated among models to retain consistency. The model simulations were objectively calibrated against observed data (streamwater: 1963 2004, soil: 1983). The ensemble of calibrated models was used to assess future response of soil and stream chemistry to reduced sulfur deposition at the HBEF. Although both hindcast (1850-1962) and forecast (2005-2100) predictions were qualitatively similar across the four models, the temporal pattern of key indicators of acidification recovery (stream acid neutralizing capacity and soil base saturation) differed substantially. The range in predictions resulted from differences in model structure and their associated posterior parameter distributions. These differences can be accommodated by employing multiple models (ensemble analysis) but have implications for individual model applications. PMID- 21028801 TI - Hyperbranched acidic polysaccharide from green tea. AB - An acidic tea polysaccharide (ALTPS), isolated from green tea ( Camellia sinensis ), was characterized as a hyperbranched glycoprotein containing the acidic heteropolysaccharide chains and the protein residues from the results of UV-vis, FTIR, one- and two-dimensional NMR, GC, GC-MS, and amino acid analyses. Solution properties of ALTPS were investigated by static and dynamic light scattering analyses and viscometry. The results indicated that the viscosity behavior of ALTPS exhibited a typical polyelectrolyte effect in distilled water, which may be avoided by adding salts. The low intrinsic viscosity of ALTPS in the solutions (8 15 mL/g) is attributed to its hyperbranched structure. By application of the polymer solution theory, it was revealed that ALTPS was present in a sphere-like conformation in the solutions as a result of the hyperbranched structure. The TEM image further confirmed that ALTPS existed in a spherical conformation in aqueous NaCl solution. Glucose was absorbed by ALTPS, which may be one of blood glucose lowering mechanisms of tea polysaccharides. PMID- 21028802 TI - Accumulation of polybrominated diphenyl ethers, hexabromobenzene, and 1,2-dibromo 4-(1,2-dibromoethyl)cyclohexane in earthworm (Eisenia fetida). Effects of soil type and aging. AB - In the present study the accumulation potentials in earthworms (Eisenia fetida) of selected brominated flame retardants (BFRs) were investigated. The tested BFRs, including polybrominated diphenyl ethers (PBDEs), hexabromobenzene (HBB), and 1,2-dibromo-4-(1,2-dibromoethyl)cyclohexane (TBECH), were found to be bioavailable to Eisenia fetida, and they accumulated in the earthworms. To our knowledge, this is the first published study to address the bioaccumulation potential of TBECH in terrestrial biota. Aging the soil resulted in decreased accumulation of TBECH, HBB, and PBDEs with six or less bromine atoms. However, no effect of soil aging was seen for BDEs 183 or 209, possibly due to their low mobility in soil. The use of different soils (artificial OECD soil and two natural Swedish soils) also affected the degree of accumulation in the worms. The results indicate that use of the generally accepted standard OECD soil may overestimate accumulation of organic contaminants by earthworms, due to high bioavailability of the contaminants and/or weight loss of the worms in it. Further, the accumulation of selected PBDEs and HBB was compared to the accumulation of their chlorinated analogues. Brominated compounds accumulated to the same or a lesser extent than their chlorinated counterparts. PMID- 21028804 TI - Free-standing highly conductive transparent ultrathin single-walled carbon nanotube films. AB - Transparent and conductive single-walled carbon nanotube (SWNT) films are of great importance to a number of applications such as optical and electronic devices. Here, we describe a simple approach for preparing free-standing highly conductive transparent SWNT films with a 20-150 nm thickness by spray coating from surfactant-dispersed aqueous solutions of SWNTs synthesized by an improved floating-catalyst growth method. After the HNO(3) treatment, dipping the SWNT films supporting on glass substrates in water resulted in a quick and nondestructive self-release to form free-standing ultrathin SWNT films on the water surface. The obtained films have sufficiently high transmittance (i.e., 95%), a very low sheet resistance (i.e., ~120 Omega/sq), and a small average surface roughness (i.e., ~3.5 nm for a displayed 10 * 10 MUm area). Furthermore, the floating SWNT films on the water surface were easily transferred to any substrates of interest, without intense mechanical and chemical treatments, to preserve their original sizes and network structures. For example, the transferred SWNT films on poly(ethylene terephthalate) films are mechanically flexible, which is a great advantage over conventional indium-tin oxide (ITO) and therefore strongly promise to be "post ITO" for many applications. PMID- 21028803 TI - Highly efficient gene silencing activity of siRNA embedded in a nanostructured gyroid cubic lipid matrix. AB - RNA interference (RNAi) is an evolutionarily conserved sequence-specific post transcriptional gene silencing pathway with wide-ranging applications in functional genomics, therapeutics, and biotechnology. Cationic liposome-small interfering RNA (CL-siRNA) complexes have emerged as vectors of choice for delivery of siRNA, which mediates RNAi. However, siRNA delivery by CL-siRNA complexes is often inefficient and accompanied by lipid toxicity. We report the development of CL-siRNA complexes with a novel cubic phase nanostructure, which exhibit efficient silencing at low toxicity. The inverse bicontinuous gyroid cubic nanostructure was unequivocally established from synchrotron X-ray scattering data, while fluorescence microscopy revealed colocalization of lipid and siRNA in complexes. We attribute the efficient silencing to enhanced fusion of complex and endosomal membranes, facilitated by the cubic phase membrane's positive Gaussian modulus, which may enable spontaneous formation of transient pores. The findings underscore the importance of understanding membrane-mediated interactions between CL-siRNA complex nanostructure and cell components in developing CL-based gene silencing vectors. PMID- 21028805 TI - Effects of inorganic and organic salts on aggregation behavior of cationic gemini surfactants. AB - All salts studied effectively reduce critical micelle concentration (CMC) values of the cationic gemini surfactants. The ability to promote the surfactant aggregation decreases in the order of C(6)H(5)COONa > p-C(6)H(4)(COONa)(2) > Na(2)SO(4)> NaCl. Moreover, only C(6)H(5)COONa distinctly reduces both the CMC values and the surface tension at CMC. For 12-4-12 solution, the penetration of C(6)H(5)COO(-) anions and charge neutralization induce a morphology change from micelles to vesicles, whereas the other salts only slightly increase the sizes of micelles. The 12-4(OH)(2)-12 solution changes from the micelle/vesicle coexistence to vesicles with the addition of C(6)H(5)COONa, whereas the other salts transfer the 12-4(OH)(2)-12 solution from the micelle/vesicle coexistence to micelles. As compared with 12-4-12, the two hydroxyls in the spacer of 12 4(OH)(2)-12 promote the micellization of 12-4(OH)(2)-12 and reduce the amounts of C(6)H(5)COONa required to induce the micelle-to-vesicle transition. PMID- 21028806 TI - Not to be toyed with. PMID- 21028808 TI - Proximity of field distribution of polycyclic aromatic hydrocarbons to chemical equilibria among air, water, soil, and sediment and its implications to the coherence criteria of environmental quality objectives. AB - The proximity of PAHs distribution to the equilibrium states among air, soil, water, and bottom sediment was assessed for future risk management and coherence test among environmental quality objectives (EQOs) in these media. Concurrently measured concentration data in the four media were used. In the study areas (Seoul, Shihwa/Banwol, and Taegu), nonequilibrium states prevailed among air, soil, and water except for some light PAHs between air and water. Elevated concentration in soil particularly caused significant deviation from equilibrium between soil and other media. Coherence criteria among these media should be determined based on steady state (not equilibrium) conditions. Sediment was in or near equilibrium with soil for all PAHs, indicating that sediment quality is closely related to soil quality and that the coherence between the EQOs of the two media is required in the study areas. As the concentration ratio of individual PAHs for a given medium pair was found to vary up to 4 orders of magnitude across the study areas, a factor of 10 as a threshold criterion for incoherence is apparently too strict to apply to the national scale of Korea. PMID- 21028809 TI - Arsenic influence on genetic variation in grain trace-element nutrient content in Bengal delta grown rice. AB - It has previously been shown that across different arsenic (As) soil environments, a decrease in grain selenium (Se), zinc (Zn), and nickel (Ni) concentrations is associated with an increase in grain As. In this study we aim to determine if there is a genetic element for this observation or if it is driven by the soil As environment. To determine the genetic and environmental effect on grain element composition, multielement analysis using ICP-MS was performed on rice grain from a range of rice cultivars grown in 4 different field sites (2 in Bangladesh and 2 in West Bengal). At all four sites a negative correlation was observed between grain As and grain Ni, while at three of the four sites a negative correlation was observed between grain As and grain Se and grain copper (Cu). For manganese, Ni, Cu, and Se there was also a significant genetic interaction with grain arsenic indicating some cultivars are more strongly affected by arsenic than others. PMID- 21028810 TI - Microtextured surfaces with gradient wetting properties. AB - Patterned surfaces with microwrinkled surface structures were prepared by thermally evaporating thin aluminum (10-300 nm thick) (Al) layers onto thick prestrained layers of a silicone elastomer and subsequently releasing the strain. This resulted in the formation of sinusoidal periodic surface wrinkles with characteristic wavelengths in the 3-42 MUm range and amplitudes as large as 3.6 +/- 0.4 MUm. The Al thickness dependence of the wrinkle wavelengths and amplitudes was determined for different values of the applied prestrain and compared to a recent large-amplitude deflection theory of wrinkle formation. The results were found to be in good agreement with theory. Samples with spatial gradients in wrinkle wavelength and amplitude were also produced by applying mechanical strain gradients to the silicone elastomer layers prior to deposition of the Al capping layers. Sessile water droplets that were placed on these surfaces were found to have contact angles that were dependent upon their position. Moreover, these samples were shown to direct the motion of small water droplets when the substrates were vibrated. PMID- 21028811 TI - Twenty second synthesis of Pd nanourchins with high electrochemical activity through an electrochemical route. AB - A rapid, templateless, surfactantless, electrochemical route is reported to synthesize uniform and clean Pd nanoparticles (~350 nm in diameter) with a substructure of sharp nanospikes (~95 nm in length). The effects of electrodeposition potential, PdCl(2) concentration, and supporting electrolyte were explored for the formation of the Pd nanourchins. The systematic studies revealed that the concentration of Pd(II) greatly affects the density of the nanospikes on the Pd nanourchins in this short-time synthesis. The substructure of the nanospikes on the nanourchins was examined to be a single-crystal quadrangular pyramid. Further investigation of the Pd nanourchins by cyclic voltammetry (CV) showed their high electrochemical activity toward formic acid oxidation. PMID- 21028812 TI - Dienyl homoallyl alcohols via palladium catalyzed ene-type reaction of aldehydes with 1,3-dienes. AB - The combination of Pd catalyst and Xantphos ligand in the presence of Et(3)B nicely promotes the allylation of aldehydes with conjugated dienes to provide dienyl homoallyl alcohols in excellent yields. The reaction occurs selectively at the C-C double bond bearing higher electron density. PMID- 21028813 TI - Water-soluble organo-silica hybrid nanotubes templated by cylindrical polymer brushes. AB - We report the preparation of water-soluble organo-silica hybrid nanotubes templated by core-shell-corona structured triblock terpolymer cylindrical polymer brushes (CPBs). The CPBs consist of a polymethacrylate backbone, a poly(tert butyl acrylate) (PtBA) core, a poly(3-(trimethoxysilyl)propyl acrylate) (PAPTS) shell, and a poly(oligo(ethylene glycol) methacrylate) (POEGMA) corona. They were prepared via the "grafting from" strategy by the combination of two living/controlled polymerization techniques: anionic polymerization for the backbone and atom transfer radical polymerization (ATRP) for the triblock terpolymer side chains. The monomers tBA, APTS, and OEGMA were consecutively grown from the pendant ATRP initiating groups along the backbone to spatially organize the silica precursor, the trimethoxysilyl groups, into a tubular manner. The synthesized core-shell-corona structured CPBs then served as a unimolecular cylindrical template for the in situ fabrication of water-soluble organo-silica hybrid nanotubes via base-catalyzed condensation of the PAPTS shell block. The formed tubular nanostructures were characterized by transmission electron microscopy (TEM), cryogenic TEM, and atomic force microscopy. PMID- 21028814 TI - Palladium-catalyzed aminosulfonylation of aryl halides. AB - The palladium-catalyzed three-component coupling of aryl iodides, sulfur dioxide, and hydrazines to deliver aryl N-aminosulfonamides is described. The colorless crystalline solid DABCO.(SO(2))(2) was used as a convenient source of sulfur dioxide. The reaction tolerates significant variation of both the aryl iodide and hydrazine coupling partners. PMID- 21028815 TI - Metabonomic investigation of liver profiles of nonpolar metabolites obtained from alcohol-dosed rats and mice using high mass accuracy MSn analysis. AB - Alcoholism is a complex disorder that, in man, appears to be genetically influenced, although the underlying genes and molecular pathways are not completely known. Here, the intragastric alcohol feeding model in rodents was used together with high mass accuracy LC-MS(n) analysis to assess the metabonomic changes in nonpolar metabolite profiles for livers from control and alcohol treated rats and mice. Ion signals with a peak area variance of less than 30% (based on repeat analysis of a pooled quality control sample analyzed throughout the batch) were submitted to multivariate statistical analysis (using principal components analysis, PCA). PCA revealed robust differences between profiles from control and alcohol-treated animals from both species. The major metabolites seen to differ between control and alcohol-treated animals were identified using high accuracy MS(n) data and verified using external search engines ( http://www.lipidmaps.org ; http://www.hmdb.ca; http://www.genome.jp/kegg/ ) and authentic standards. The main metabolite classes to show major changes in the alcoholic liver-derived samples were fatty acyls, fatty acid ethyl esters, glycerolipids, and phosphatidylethanol homologues. Significant metabolites that were up-regulated by alcohol treatment in both rat and mouse livers included fatty acyls, metabolites such as octadecatrienoic acid and eicosapentaenoic acid, a number of fatty acid ethyl esters such as ethyl arachidonate, ethyl docosahexaenoic acid, ethyl linoleate, and ethyl oleate and phosphatidylethanol (PEth) homologues (predominantly PEth 18:0/18:2 and PEth 16:0/18:2; PEth homologues are currently considered as potential biomarkers for harmful and prolonged alcohol consumption in man). A number of glycerophospholipids resulted in both up-regulation (m/z 903.7436 [M + H](+) corresponding to a triglyceride) and down-regulation (m/z 667.5296 [M + H](+) corresponding to a diglyceride). Metabolite profiles were broadly similar in both mouse and rat models. However, there were a number of significant differences in the alcohol-treated group particularly in the marked down-regulation of retinol and free cholesterol in the mouse compared to the rat. Unique markers for alcohol treatment included ethyl docosahexaenoic acid. Metabolites were identified with high confidence using predominantly negative ion MS(n) data for the fatty acyl components to match to www.lipidmaps.org MS and MS/MS databases; interpreting positive ion data needed to take into account possible adduct ions which may confound the identification of other lipid classes. The observed changes in lipid profiles were consistent with alcohol-induced liver injury in humans. PMID- 21028816 TI - Solanum nigrum Linn. water extract inhibits metastasis in mouse melanoma cells in vitro and in vivo. AB - Metastatic melanoma is an aggressive skin cancer notoriously resistant to current cancer therapies. Thus, new treatment strategies are urgently needed. Solanum nigrum Linn., commonly used in Oriental medicine, has showed antineoplastic activity in human cancer cell lines. The aim of this study was to evaluate the inhibitive effect of S. nigrum Linn. water extract (SNWE) on melanoma metastasis and dissect the underlying mechanisms of SNWE actions. B16-F1 cells were analyzed for migrating and invasive abilities with SNWE treatment, and several putative targets involved in metastatic melanoma were examined. In parallel, primary mouse xenograft and lung metastasis of melanoma models were established to examine the therapeutic potential of SNWE. The results indicated SNWE significantly inhibited B16-F1 cell migration and invasion. Meanwhile, decreased Akt activity and PKCalpha, Ras, and NF-kappaB protein expressions were detected in dose-dependent manners. In line with this notion, >50% reduced tumor weight and lung metastatic nodules were observed in 1% SNWE fed mice. This was associated with reduced serum MMP-9 as well as Akt activity and PKCalpha, Ras, and NF-kappaB protein expressions. Thus, this work indicates SNWE has potential application for treating metastatic melanoma. PMID- 21028817 TI - A specific interaction of L-tryptophan with CO of CO-bound indoleamine 2,3 dioxygenase identified by resonance Raman spectroscopy. AB - Indoleamine 2,3-dioxygenase (IDO) is a heme enzyme which catalyzes dioxygenation of l-Trp (tryptophan), yielding N-formylkynurenine. IDO thus plays a key role in l-Trp catabolism in mammals. In the present study, resonance Raman (RR) spectra of the reduced carbon monoxide- (CO-) bound form of IDO were measured in order to gain insights into the active site environment of O(2). Binding of CO to l-Trp bound IDO causes a significant change in the electronic and RR spectra of the heme, indicating that the pi* orbitals of the carbon atom of CO interact with pi orbitals of Fe and the porphyrin. On the other hand, binding of CO to d-Trp-bound IDO does not induce the same change. This is also the case with substrate-free IDO. Based on the distinct absorption spectra and RR bands of the vibrational signature of CO (nu(CO), delta(FeCO), and nu(Fe-CO)) of the l-Trp-bound species relative to the other two species, it is confirmed that sterically constrained geometry of the Fe-O-O unit exists as previously reported (Terentis, A. C., et al. (2002) J. Biol. Chem. 277, 15788-15794). In contrast, binding of d-Trp does not induce such constraint. The comparable values of V(max) reported for l-Trp and d-Trp are interpreted as a result of a change in the rate-limiting step in the reaction cycle of the enzyme induced by the d-enantiomer relative to the l enantiomer. Enhancements of the overtone and the combination Raman modes of the Fe-CO stretching vibration are evident. The anharmonicity of the Fe-CO stretching oscillator is significantly higher than those of oxygen carrier proteins. This is a specific character of IDO and might be responsible for the unique reactivity of this enzyme. PMID- 21028818 TI - Pickering emulsion templated interfacial atom transfer radical polymerization for microencapsulation. AB - This Article describes a new microencapsulation method based on a Pickering emulsion templated interfacial atom transfer radical polymerization (PETI-ATRP). Cationic LUDOX CL nanoparticles were coated electrostatically with an anionic polymeric ATRP initiator, poly(sodium styrene sulfonate-co-2-(2 bromoisobutyryloxy)ethyl methacrylate) (PSB), prepared by radical copolymerization of sodium styrene sulfonate and 2-(2-bromoisobutyryloxy)ethyl methacrylate (BIEM). The resulting PSB-modified CL particles were surface active and could be used to stabilize oil-in-water Pickering emulsions. ATRP of water soluble cross-linking monomers, confined to the oil-water interface by the surface-bound PSB, then led to nanoparticle/polymer composite shells. This method allowed encapsulation of core solvents (xylene, hexadecane, perfluoroheptane) with different solubility parameters. The microcapsule (MC) wall chemistry could accommodate different monomers, demonstrating the versatility of this method. Double-walled MCs were formed by sequentially carrying out PETI-ATRP and in situ polymerization of encapsulated monomers. The double-walled structure was verified by both transmission electron microscopy (TEM) and scanning transmission X-ray microscopy (STXM). PMID- 21028819 TI - Enantioselective desymmetrization of cyclopropenes by hydroacylation. AB - We report an enantioselective desymmetrization of cyclopropenes by intermolecular Rh-catalyzed hydroacylation. Cyclopropylketones, bearing quaternary stereocenters, are produced with diastereocontrol (up to >20:1) and excellent enantiomeric excess (up to >99 ee). PMID- 21028820 TI - Amplified fluorescent recognition of g-quadruplex folding with a cationic conjugated polymer and DNA intercalator. AB - The single stranded DNA (ssDNA) with G-rich sequence can fold into G-quadruplex via intramolecular hydrogen-bonding interaction in the presence of ligand. This structure conversion can be specifically detected by a fluorescence method based on different interaction between SYBR Green I (SG) and various DNA structures. SG is proved to intercalate into G-quadruplex and results in high fluorescence intensity, which can be further amplified by 6-fold through fluorescence resonance energy transfer (FRET) from a water-soluble cationic conjugated polymer (CCP) to SG due to the high affinity of positively charged CCP to negatively charged rigid G-quadruplex, whereas it is not performed for ssDNA in the absence of K(+). As a result, the ssDNA/SG/CCP complex can be used to detect potassium ions with improved selectivity in a label-free and cost-effective manner. PMID- 21028821 TI - GMI, a Ganoderma immunomodulatory protein, down-regulates tumor necrosis factor alpha-induced expression of matrix metalloproteinase 9 via NF-kappaB pathway in human alveolar epithelial A549 cells. AB - Matrix metalloproteinase 9 (MMP-9) has been implicated in airway injury in chronic obstructive pulmonary disease (COPD), lung inflammation, and lung cancer and plays a major role in tumor necrosis factor-alpha (TNF-alpha)-stimulated tumor invasion and lung inflammation. MMP-9 activity is promoted by the pro inflammatory cytokine TNF-alpha. GMI, cloned from Ganoderma microsporum and purified, is one of the recombinant fungal immunomodulatory proteins. To understand the molecular mechanisms involved in the suppression of TNF-alpha mediated tumor invasion and inflammation, GMI modulation of this pathway was investigated in human alveolar epithelial A549 cells in this study. GMI exhibited an inhibitory effect on TNF-alpha-induced invasion, with GMI treatment and TNF alpha exposure presenting the most anti-invasive properties on Boyden chamber assay. GMI reduced TNF-alpha-induced MMP-9 activities on gelatin zymography assay through inhibition of MMP-9 transcriptional activity. RT-PCR and MMP-9 promoter luciferase analysis revealed that GMI inhibits the transcription of MMP-9 mRNA. Moreover, in vitro and in vivo binding experiments, an electrophoretic mobility shift assay (EMSA), and chromatin immunoprecipitation assay (ChIP) demonstrated that GMI suppresses DNA binding of nuclear factor (NF)-kappaB transcription factors to MMP-9 promoter. Western blot analysis indicated that GMI blocks the phosphorylation and degradation of IkappaBalpha, which in turn leads to suppression of the phosphorylation and nuclear translocation of p65. Thus, overall, our results indicated that GMI mediates antitumor invasion and anti inflammatory effects through modulation of NF-kappaB/MMP-9 pathways. PMID- 21028822 TI - Effect of addition of commercial grape seed tannins on phenolic composition, chromatic characteristics, and antioxidant activity of red wine. AB - The effect of addition of grape seed tannins on the phenolic composition, chromatic characteristics, and antioxidant activity of red wine was studied. Two highly pure commercial grape seed tannins (GSE100 and GSE300) were selected, and their phenolic compositions were determined. Two types of red wines were made with Castelao/Tinta Miuda (3/2, w/w) grapevine varieties by fermentation on skin using two different maceration times, which correspond to the wines rich and poor in polyphenols, respectively. Each of these wines was used for experimentation with the addition of GSE100 and GSE300 before and immediately after alcoholic fermentation. Phenolic composition, chromatic characteristics, and antioxidant activity of the finished red wines were analyzed by HPLC-DAD, CIElab 76 convention, and DPPH radical test, respectively. The results showed that the addition of grape seed tannins had obvious effects of increasing color intensity and antioxidant activity only in the wines poor in polyphenols. Although GSE300 contained much higher amounts of di- and trimer procyanidins and a lower amount of polymeric proanthocyanidins, it provided effects of increasing the color intensity and antioxidant activity of the wines poor in polyphenols similar to those of GSE100. Furthermore, GSE100 released more gallic acid to wines than GSE300, although no gallic acid was detected in GSE100. Tannins added after alcoholic fermentation had a better effect on phenolic composition of red wine than tannins added before alcoholic fermentation. PMID- 21028823 TI - Intramolecular hydroamination/cyclization of aminoalkenes catalyzed by Ln[N(SiMe(3))(2)](3) grafted onto periodic mesoporous silicas. AB - Homoleptic rare-earth metal silylamide complexes Ln[N(SiMe(3))(2)](3) (Ln = Y, La, Nd) were grafted onto a series of partially dehydroxylated periodic mesoporous silica (PMS) supports, SBA-15(-500) (d(p) = 7.9 nm), SBA-15LP(-500) (d(p) = 16.6 nm), and MCM-41(-500) (d(p) = 4.1 nm). The hybrid materials Ln[N(SiMe(3))(2)](3)@PMS efficiently catalyze the intramolecular hydroamination/cyclization reaction of 2,2-dimethyl-4-penten-1-amine. Under the prevailing slurry conditions the metal size (Y > La > Nd), the pore size, and the particle morphology affect the catalytic performance. Material Y[N(SiMe(3))(2)](3)@SBA-15LP(-500) displayed the highest activity (TOF = up to 420 h(-1) at 60 degrees C), with the extralarge pores minimizing restrictive product inhibition and substrate diffusion effects. The catalytic activity of Y[N(SiMe(3))(2)](3)@SBA-15LP(-500) is found to be much higher than that of the molecular counterpart (TOF = up to 54 h(-1)), and its recyclability is demonstrated. PMID- 21028824 TI - Improved characterization of the botanical origin of sugar by carbon-13 SNIF-NMR applied to ethanol. AB - Until now, no analytical method, not even isotopic ones, had been able to differentiate between sugars coming from C4-metabolism plants (cane, maize, etc.) and some crassulacean acid metabolism plants (e.g., pineapple, agave) because in both cases the isotope distributions of the overall carbon-13/carbon-12 and site specific deuterium/hydrogen isotope ratios are very similar. Following recent advances in the field of quantitative isotopic carbon-13 NMR measurements, a procedure for the analysis of the positional carbon-13/carbon-12 isotope ratios of ethanol derived from the sugars of pineapples and agave using the site specific natural isotopic fractionation-nuclear magnetic resonance (SNIF-NMR) method is presented. It is shown that reproducible results can be obtained when appropriate analytical conditions are used. When applied to pineapple juice, this new method demonstrates a unique ability to detect cane and maize sugar, which are major potential adulterants, with a detection limit in the order of 15% of the total sugars, which provides an efficient mean of controlling the authenticity of juices made from this specific fruit. When applied to tequila products, this new method demonstrates a unique ability to unambiguously differentiate authentic 100% agave tequila, as well as misto tequila (made from at least 51% agave), from products made from a larger proportion of cane or maize sugar and therefore not complying with the legal definition of tequila. PMID- 21028825 TI - Preparation and evaluation of carborane analogues of tamoxifen. AB - A stereoselective synthesis of closo carborane analogues of tamoxifen was developed where the products represent a new approach to developing metabolically robust SERMs. The A-ring found in the backbone of tamoxifen was replaced with an ortho carborane cluster; the product was determined to be the desired Z isomer, which showed superior chemical stability to tamoxifen both in solution and in the solid state. By use of microwave heating, it was possible to convert some of the Z carborane tamoxifen analogue to the corresponding E isomer. Cell growth assays using both isomers and a carborane that is known to target the ER were conducted using estrogen receptor (ER) positive and ER negative human breast cancer cells with and without the presence of estradiol (E2). The Z carborane isomer was able to inhibit cell proliferation better than tamoxifen in an E2 free environment, while the E isomer inhibited cell growth better than tamoxifen when E2 was present. PMID- 21028826 TI - Desorption electrospray ionization mass spectrometry of glycosaminoglycans and their protein noncovalent complex. AB - Glycosaminoglycans heparin and heparan sulfate are biologically active polysulfated carbohydrates that are among the most challenging biopolymers with regards to their structural analysis and functional assessment. Fragmentation of oligosaccharides and sulfate loss are important hindrance to their analysis by mass spectrometry (MS), requiring thus soft ionization methods. The recently introduced soft ionization method desorption electrospray ionization (DESI) has been applied here to heparin and heparan sulfate oligosaccharides, showing that DESI-MS is well suited for the detection of such fragile biomolecules in their intact form. Characterization of complicated oligosaccharides such as synthetic heparin octadecasulfated dodecasaccharide was successfully achieved. The use of water for a spray solvent instead of denaturing organic solvents allowed the first DESI-MS detection of noncovalent biomolecular complexes between heparin oligosaccharides and the chemokine Stromal Cell-derived Factor-1. The hyphenation of the DESI ion source with the high-resolution LTQ-Orbitrap MS analyzer led to high accuracy of mass measurement and enabled unambiguous determination of the protein-bound sulfated oligosaccharide. PMID- 21028827 TI - Effects on molecular conformation and anticoagulant activities of 1,6 anhydrosugars at the reducing terminal of antithrombin-binding octasaccharides isolated from low-molecular-weight heparin enoxaparin. AB - Terminal 1,6-anhydro-aminosugars (1,6-anAS) are typical structural moieties of enoxaparin, a low-molecular-weight heparin (LMWH) widely used for prevention and treatment of thrombotic disorders. In the enoxaparin manufacturing process, these modified amino sugars are formed during the beta-eliminative cleavage of heparin. To investigate the effect of terminal anAS on antithrombin (AT) binding and on inhibition of factor Xa (FXa), two octasaccharides containing modified AT-binding pentasaccharide sequences were isolated from enoxaparin. The molecular conformation of the octasaccharides terminating with N-sulfo-1,6-anhydro-D mannosamine and N-sulfo-1,6-anhydro-D-glucosamine, respectively, has been determined both in the absence and presence of AT by NMR experiments and docking simulations. Reduced overall contacts of the terminal anAS residues with the binding region of AT induce a decrease in affinity for AT as well as lower anti FXa activity. The anti-FXa measured either in buffer or plasma milieu does not show any significant difference, suggesting that the inhibition of anti-FXa remains specific and biologically relevant. PMID- 21028828 TI - Design of three-component vaccines against group A streptococcal infections: importance of spatial arrangement of vaccine components. AB - Immunological assessment of group A streptococcal (GAS) branched lipopeptides demonstrated the impact of spatial arrangement of vaccine components on both the quality and quantity of their immune responses. Each lipopeptide was composed of three components: a GAS B-cell epitope (J14), a universal CD4(+) T-cell helper epitope (P25), and an immunostimulant lipid moiety that differs only in its spatial arrangement. The best systemic immune responses were demonstrated by a lipopeptide featuring the lipid moiety at the lipopeptide C-terminus. However, this candidate did not achieve protection against bacterial challenge. The best protection (100%) was shown by a lipopeptide featuring a C-terminal J14, conjugated through a lysine residue to P25 at the N-terminus, and a lipid moiety on the lysine side chain. The former candidate features alpha-helical conformation required to produce protective J14-specific antibodies. Our results highlight the importance of epitope orientation and lipid position in the design of three-component synthetic vaccines. PMID- 21028829 TI - Side chain cyclization based on serine residues: synthesis, structure, and activity of a novel cyclic analogue of the parathyroid hormone fragment 1-11. AB - The N-terminal region of the parathyroid hormone (PTH) is sufficient to activate the G-protein-coupled PTH receptor 1 (PTHR1). The shortest PTH analogue displaying nanomolar potency is the undecapeptide H-Aib-Val-Aib-Glu-Ile-Gln-Leu Nle-His-Gln-Har-NH(2) that contains two helix-stabilizing residues (Aib(1,3)). To increase the helical character and proteolytic stability of this linear peptide, we replaced Gln(6,10) with (a) Lys(6) and Glu(10) to introduce a lactam bridge and (b) Ser(6,10) to form a diester bridge upon cross-linking with adipic acid. These cyclopeptides were, respectively, 468-fold less and 12-fold more potent agonists than the linear analogue. Despite their different potencies, all three analogues adopted similar alpha-helix structures, as shown by NMR and molecular dynamics studies. However, the diester bridge could better mimic the orientation and chemical properties of the side chains of Gln(6) and Gln(10) in the linear PTH analogue than the lactam moiety. This is apparently important for efficient receptor activation and provides further insights into the receptor-bound ligand conformation. PMID- 21028830 TI - Optimization of matrix conditions for the control of MALDI in-source decay of permethylated glycans. AB - Due to its fastness and its easiness to use, MALDI-MS is currently an analytical tool widely used in glycomic applications. However, the MALDI ionization process could result in the so-called "in-source decay", or ISD, of analytes, leading to complex spectra. On the other hand, ISD opens the possibility to perform pseudo MS(3) experiments. This phenomenon must therefore be controlled in order to be used on demand as a supplementary tool for the analysis of permethylated glycans by MALDI mass spectrometry. For this purpose, several matrices were tested and MALDI imaging was used to determine optimal conditions promoting or, inversely, avoiding ISD of permethylated glycans. 2,5-DHB was shown to be a versatile matrix allowing one to induce or prevent ISD according to the location of laser shots. Inversely, it was shown that 9-aminoacridine forms homogeneous spots and avoids completely ISD. This matrix would therefore be suitable for automatic analysis. PMID- 21028831 TI - Effect and limitation of excess ammonium on the release of O-glycans in reducing forms from glycoproteins under mild alkaline conditions for glycomic and functional analysis. AB - Ammonium-based alkali-catalyzed beta-elimination under nonreducing conditions was investigated in detail for the stability of the released mucin-type O-glycan chains with beta1,3-linked cores. In contrast to the previously studied beta1,4 linkage of the N-glycan-type, which was shown to be stable under the ammonium based alkaline conditions, the beta1,3-linkage is labile toward alkaline treatment and considerable peeling was observed with both model heptasaccharides and standard glycoproteins. The former include eight reducing glucoheptasaccharides with different and commonly occurring linkages (alpha1,2-, beta1,2-, alpha1,3-, beta1,3-, alpha1,4-, beta1,4-, alpha1,6-, and beta1,6 linkages), and the latter include mucin-type bovine submaxillary mucin and bovine fetuin, which contains both O- and N-glycans. The results indicated that complete prevention of peeling under nonreducing alkali-catalyzed hydrolysis conditions remains difficult. The yields of released O- and N-glycans were also assessed by use of the two glycoproteins as models. Compared with conventional procedures, Carlson degradation for O-glycan release and PNGase F digestion for N-glycan release, the nonreducing ammonium-based alkaline hydrolysis gave lower yields. Great care has to be taken when employing such nonreducing alkaline conditions in glycomic analysis and in obtaining glycoprotein glycans for functional studies. PMID- 21028832 TI - Folding equilibrium constants of telomere G-quadruplexes in free state or associated with proteins determined by isothermal differential hybridization. AB - Guanine rich (G-rich) nucleic acids form G-quadruplex structures that are implicated in many biological processes, pharmaceutical applications, and molecular machinery. The folding equilibrium constant (K(F)) of the G-quadruplex not only determines its stability and competition against duplex formation in genomic DNA but also defines its recognition by proteins and drugs and technical specifications. The K(F) is most conveniently derived from thermal melting analysis that has so far yielded extremely diversified results for the human telomere G-quadruplex. Melting analysis cannot be used for nucleic acids associated with proteins, thus has difficulty to study how protein association affects the folding equilibrium of G-quadruplex structure. In this work, we established an isothermal differential hybridization (IDH) method that is able to determine the K(F) of G-quadruplex, either alone or associated with proteins. Using this method, we studied the folding equilibrium of the core sequence G(3)(T(2)AG(3))(3) from vertebrate telomere in K(+) and Na(+) solutions and how it is affected by proteins associated at its adjacent regions. Our results show that the K(F) obtained for the free G-quadruplex is within 1 order of magnitude of most of those obtained by melting analysis and protein binding beside a G quadruplex can dramatically destabilize the G-quadruplex. PMID- 21028834 TI - Nanocarbon-induced rapid transformation of polymer surfaces into superhydrophobic surfaces. AB - We present a facile method for fabricating superhydrophobic polymer surfaces by solubility modulation and nanocarbon (NC)-induced crystallization of polycarbonate (PC). The method consists of dipping polymer sheets in a solvent in which the polymer is partially soluble and then inducing solution crystallization by dipping the sheet in a poor solvent for several seconds. A solvent mixture of methyl ethyl ketone and isopropyl alcohol (IPA) was optimized to shorten the crystallization time in a poor solvent. Single-walled carbon nanotubes, multiwalled carbon nanotubes (MWNTs), and graphene sheets were used to nucleate PC crystallization. In particular, monolayer graphene sheets were prepared by reducing graphene oxide with hydrazine. Crystalline micro- and nanostructures rapidly formed upon dipping of the PC sheets in the solution containing NCs, followed by immersion in IPA. The structures depended on the dimensions of the NCs. Especially, in the MWNT solution, dipping for 10 s was sufficient to create a superhydrophobic surface. Crystallization of PC and the incorporation of NCs during crystallization were characterized by Raman spectroscopy. PMID- 21028833 TI - Quantitative measurement of urinary excretion of 3-hydroxyisovaleryl carnitine by LC-MS/MS as an indicator of biotin status in humans. AB - Abnormally increased urinary excretion of 3-hydroxyisovaleryl carnitine (3HIA carnitine) results from impairment in leucine catabolism caused by reduced activity of the biotin-dependent enzyme 3-methylcrotonyl-CoA carboxylase. Accordingly, urinary 3HIA-carnitine might reflect biotin status. Here, we describe an LC-MS/MS method for accurately quantitating the urinary concentration of 3HIA-carnitine at concentrations that are typical for excretion rates that are normal or only modestly increased. This method allows for high sample throughput and does not require solid-phase extraction. We used this method to provide evidence validating urinary 3HIA-carnitine as a biomarker of biotin deficiency in humans. Four healthy adult subjects were successfully made marginally biotin deficient by feeding a 30% egg white diet for 28 days. From study day 0 to 28, the mean urinary excretion of 3HIA-carnitine increased 3.5-fold (p = 0.026). These preliminary results indicate that urinary excretion of 3HIA-carnitine increases with marginal biotin deficiency. If these results are confirmed in studies involving larger numbers of subjects, urinary excretion of 3HIA-carnitine may potentially be a clinically useful indicator of biotin status. PMID- 21028835 TI - Achieving 50% ionization efficiency in subambient pressure ionization with nanoelectrospray. AB - Inefficient ionization and poor transmission of the charged species produced by an electrospray from the ambient pressure mass spectrometer source into the high vacuum region required for mass analysis significantly limits achievable sensitivity. Here, we present evidence that, when operated at flow rates of 50 nL/min, a new electrospray-based ion source operated at ~20 Torr can deliver ~50% of the analyte ions initially in the solution as charged desolvated species into the rough vacuum region of mass spectrometers. The ion source can be tuned to optimize the analyte signal for readily ionized species while reducing the background contribution. PMID- 21028836 TI - High-aspect-ratio, silicon oxide-enclosed pillar structures in microfluidic liquid chromatography. AB - The present paper discusses the ability to separate chemical species using high aspect-ratio, silicon oxide-enclosed pillar arrays. These miniaturized chromatographic systems require smaller sample volumes, experience less flow resistance, and generate superior separation efficiency over traditional packed bed liquid chromatographic columns, improvements controlled by the increased order and decreased pore size of the systems. In our distinctive fabrication sequence, plasma-enhanced chemical vapor deposition (PECVD) of silicon oxide is used to alter the surface and structural properties of the pillars for facile surface modification while improving the pillar mechanical stability and increasing surface area. The separation behavior of model compounds within our pillar systems indicated an unexpected hydrophobic-like separation mechanism. The effects of organic modifier, ionic concentration, and pressure-driven flow rate were studied. A decrease in the organic content of the mobile phase increased peak resolution while detrimentally effecting peak shape. A resolution of 4.7 (RSD = 3.7%) was obtained for nearly perfect Gaussian shaped peaks, exhibiting plate heights as low as 1.1 and 1.8 MUm for fluorescein and sulforhodamine B, respectively. Contact angle measurements and DART mass spectrometry analysis indicate that our employed elastomeric soft bonding technique modifies pillar properties, creating a fortuitous stationary phase. This discovery provides evidence supporting the ability to easily functionalize PECVD oxide surfaces by gas-phase reactions. PMID- 21028837 TI - Label-free detection of clustering of membrane-bound proteins. AB - We report a new and label-free method to detect and characterize the clustering of membrane-bound proteins and, by extension, the lateral segregation of nanosized particles adsorbed to planar surfaces in liquid environment. The method exploits the contrast between two different mass and surface sensitive detection methods, quartz crystal microbalance with dissipation monitoring and ellipsometry. The time-resolved correlation of both techniques provides insight into subtle changes in the clustering state of surface-bound molecules that is not accessible with either technique alone. A theoretical model can provide quantitative predictions about the size of surface-bound clusters. PMID- 21028838 TI - Dithiapyrannylidenes as efficient hole collection interfacial layers in organic solar cells. AB - One inherent limitation to the efficiency of photovoltaic solar cells based on polymer/fullerene bulk heterojunctions (BHJs) is the accumulation of positive charges at the anodic interface. The unsymmetrical charge collection of holes and electrons dramatically decreases the short-circuit current. Interfacial layers (IFLs) such as poly(3,4-ethylenedioxythiophene):poly(4-styrenesulfonate) have no effect on the unbalanced electron/hole transport across the BHJ. We report here on the use of dithiapyrannylidenes (DITPY), a new class of planar quinoid compounds, as efficient hole-transporting/electron-blocking layers in organic solar cells based on poly(3-hexylthiophene)/[6,6]-phenyl-C(61)-butyric acid methyl ester (P3HT:PCBM) BHJs. Inserting a 15-nm-thick IFL of 4,4'-bis(diphenyl 2,6-thiapyrannylidene) (DITPY-Ph(4)) between the indium-tin oxide electrode and the P3HT:PCBM BHJ prevents detrimental space-charge effects and favors recombination-limited currents. Current-sensing atomic force microscopy reveals a drastic increase of the hole-carrying pathways in DITPY-Ph(4) compared to PEDOT:PSS. In ambient conditions, photovoltaic cells using DITPY-Ph(4) exhibit an 8% increase in the current density, although the conversion efficiency remains slightly lower compared to PEDOT:PSS-based devices. Finally, we present a detailed analysis of the photocurrent generation, showing that DITPY-Ph(4) IFLs induce a transition from unproductive space-charge-limited currents to recombination-limited currents. PMID- 21028839 TI - Hygroscopic behavior of individual submicrometer particles studied by X-ray spectromicroscopy. AB - A novel application of single particle scanning transmission X-ray microscopy (STXM) and near edge X-ray absorption fine structure (NEXAFS) spectroscopy is presented for quantitative analysis of hygroscopic properties and phase transitions of individual submicrometer particles. The approach utilizes the exposure of substrate-deposited individual particles to water vapor at different relative humidity followed by STXM/NEXAFS spectromicroscopy analysis. The hygroscopic properties of atmospherically relevant NaCl, NaBr, NaI, and NaNO(3) submicrometer particles were measured to evaluate the utility of the approach. An analytical approach for quantification of a water-to-solute ratio within an individual submicrometer particle during hydration and dehydration cycles is presented. The results for the deliquescence and efflorescence phase transitions and quantitative measurements of water-to-solute ratios are found in excellent agreement with available literature data. Oxygen K-edge NEXAFS spectra of submicrometer sodium halide droplets are reported along with a unique experimental observation of the formation of the halide-water anionic complex in NaBr and NaI microdimensional droplets. The analytical approach provides a unique opportunity for spectromicroscopy studies of water uptake on environmental particles collected in both laboratory and field studies. PMID- 21028840 TI - Organic field-effect transistor/memory devices with pentacene/polydiacetylene composite film as active channel material: a morphology dependence study. AB - Composite films of pentacene and poly(10,12-pentacosadiynoic acid) were prepared and used as the active channel material in a top-contact, bottom-gate field effect transistor. The transistors exhibited high field-effect mobility as well as large I-V hysteresis as a function of gate bias history. The polydiacetylenic moieties incorporated in the pentacene film served as charge storage vehicles, which affected the threshold voltage shifts and created the electric bistability needed in a memory device. The memory window, response, and retention highly depend on the morphology of the polydiacetylene film buried under. Detailed film structure analyses and correlation with the transistor/memory property are provided. PMID- 21028841 TI - Novel hydrophilic bis(1,2,3-triazolyl)fluorenyl probe for in vitro zinc ion sensing. AB - A hydrophilic bis(1,2,3-triazolyl)fluorene derivative was synthesized as a multi photon-absorbing, zinc-ion-sensing fluorescent probe. The fluorescence response was approximately five-fold greater in presence of Zn(2+), resulting in a large binding constant (1 * 10(9)) for a 1:2 ligand to zinc complex. A four-fold increase in the two-photon absorption cross section was achieved upon binding Zn(2+). In vitro two-photon fluorescence microscopy imaging revealed a significant fluorescence increase upon introduction of Zn(2+) into HeLa cells and reversible Zn(2+) binding, demonstrating the potential of this probe for zinc ion sensing. PMID- 21028842 TI - Hydrogen-bonding-promoted oxidative addition and regioselective arylation of olefins with aryl chlorides. AB - The first, general, and highly efficient catalytic system that allows a wide range of activated and unactivated aryl chlorides to couple regioselectively with olefins has been developed. The Heck arylation reaction is likely to be controlled by the oxidative addition of ArCl to Pd(0). Hence, an electron-rich diphosphine, 4-MeO-dppp, was introduced to facilitate the catalysis. Solvent choice is critical, however; only sluggish arylation is observed in DMF or DMSO, whereas the reaction proceeds well in ethylene glycol at 0.1-1 mol % catalyst loadings, displaying excellent regioselectivity. Mechanistic evidence supports that the arylation is turnover-limited by the oxidative addition step and, most importantly, that the oxidative addition is accelerated by ethylene glycol, most likely via hydrogen bonding to the chloride at the transition state as shown by DFT calculations. Ethylene glycol thus plays a double role in the arylation, facilitating oxidative addition and promoting the subsequent dissociation of chloride from Pd(II) to give a cationic Pd(II)-olefin species, which is key to the regioselectivity observed. PMID- 21028843 TI - Self-assembly and biomaterials. AB - An interesting field within the broad subject of biomaterials is the chemical and physical crafting of materials that can functionally substitute or help regenerate the organs and tissues of the human body. Regeneration is the new dimension of this field as opposed to the more established area of permanent implants and devices to substitute natural structures and functions. With the advent of nanoscience, the field is experiencing a renaissance by embracing the vision that artificial nanostructures of the self-assembling type could be designed for highly specific functions to promote regenerative processes. PMID- 21028844 TI - Endo- and exocytosis of zwitterionic quantum dot nanoparticles by live HeLa cells. AB - Uptake and intracellular transport of D-penicillamine coated quantum dots (DPA QDs) of 4 nm radius by live HeLa cells have been investigated systematically by spinning disk and 4Pi confocal microscopies. Unlike larger nanoparticles, these small DPA-QDs were observed to accumulate at the plasma membrane prior to internalization, and the uptake efficiency scaled nonlinearly with the nanoparticle concentration. Both observations indicate that a critical threshold density has to be exceeded for triggering the internalization process. By using specific inhibitors, we showed that DPA-QDs were predominantly internalized by clathrin-mediated endocytosis and to a smaller extent by macropinocytosis. Clusters of DPA-QDs were found in endosomes, which were actively transported along microtubules toward the perinuclear region. Later on, a significant fraction of endocytosed DPA-QDs were found in lysosomes, while others were actively transported to the cell periphery and exocytosed with a half-life of 21 min. PMID- 21028845 TI - Distinct polymer architecture mediates switching of complement activation pathways at the nanosphere-serum interface: implications for stealth nanoparticle engineering. AB - Nanoparticles with surface projected polyethyleneoxide (PEO) chains in "mushroom brush" and "brush" configurations display stealth properties in systemic circulation and have numerous applications in site-specific targeting for controlled drug delivery and release as well as diagnostic imaging. We report on the "structure-activity" relationship pertaining to surface-immobilized PEO of various configurations on model nanoparticles, and the initiation of complement cascade, which is the most ancient component of innate human immunity, and its activation may induce clinically significant adverse reactions in some individuals. Conformational states of surface-projected PEO chains, arising from the block copolymer poloxamine 908 adsorption, on polystyrene nanoparticles trigger complement activation differently. Alteration of copolymer architecture on nanospheres from mushroom to brush configuration not only switches complement activation from C1q-dependent classical to lectin pathway but also reduces the level of generated complement activation products C4d, Bb, C5a, and SC5b-9. Also, changes in adsorbed polymer configuration trigger alternative pathway activation differently and through different initiators. Notably, the role for properdin mediated activation of alternative pathway was only restricted to particles displaying PEO chains in a transition mushroom-brush configuration. Since nanoparticle-mediated complement activation is of clinical concern, our findings provide a rational basis for improved surface engineering and design of immunologically safer stealth and targetable nanosystems with polymers for use in clinical medicine. PMID- 21028846 TI - Thermo-induced electromagnetic coupling in gold/polymer hybrid plasmonic structures probed by surface-enhanced raman scattering. AB - This paper describes a general stepwise strategy combining diazonium salt, surface-initiated atom transfer radical polymerization (SI-ATRP), and click chemistry for an efficient gold surface functionalization by poly(N isopropylacrylamide) (PNIPAM) brushes and gold nanoparticle assemblies. We designed by this way a new plasmonic device made of gold nanoparticles separated from a gold film through a thermoresponsive polymer layer. This organic layer responds to temperature variations by conformational changes (with a characteristic temperature called the lower critical solution temperature, LCST) and is therefore able to vary the distance between the gold nanoparticles and the gold film. The optical properties of these stimulable substrates were probed by surface-enhanced raman scattering (SERS) using methylene blue (MB) as a molecular probe. We show that an increase of the external temperature reversibly induces a significant enhancement of the MB SERS signal. This was attributed to a stronger interaction between the gold nanoparticles and the gold substrate. The temperature-responsive plasmonic devices developed in this paper thus provide a dynamic SERS platform, with thermally switchable electromagnetic coupling between the gold nanoparticles and the gold surface. PMID- 21028847 TI - Self-assembly and its impact on interfacial charge transfer in carbon nanotube/P3HT solar cells. AB - Charge transfer at the interface of conjugated polymer and nanoscale inorganic acceptors is pivotal in determining the efficiency of excitonic solar cells. Despite intense efforts, carbon nanotube/polymer solar cells have resulted in disappointing efficiencies (<2%) due in large part to poor charge transfer at the interface. While the interfacial energy level alignment is clearly important, the self-assembly and the interface structure also play a major role in facilitating this charge transfer. To understand and control this effect to our advantage, we study the interface of commonly used conductive polymer poly-3-hexylthiophene (P3HT) and single-walled carbon nanotubes (SWNTs) with a combination of molecular dynamics simulations, absorption spectra experiments, and an analysis of charge transfer effects. Classical molecular dynamics simulations show that the P3HT wraps around the SWNTs in a number of different conformations, including helices, bundles, and more elongated conformations that maximize planar pi-pi stacking, in agreement with recent experimental observations. Snapshots from the MD simulations reveal that the carbon nanotubes play an important templating role of increasing the pi-conjugation in the system, an effect deriving from the pi-pi stacking interaction at the interface and the 1-dimensional (1D) nature of the SWNTs, and independent of the SWNT chirality. We show how this increase in the system conjugation could largely improve the charge transfer in P3HT-SWNT type II heterojunctions and support our results with absorption spectra measurements of mixtures of carbon nanotubes and P3HT. These findings open possibilities for improved preparation of polymeric solar cells based on carbon nanotubes and on 1D nanomaterials in general. PMID- 21028848 TI - First-row transition metal complexes of the strongly donating pentadentate ligand PY4Im. AB - The new ligand PY4Im, which incorporates an axial N-heterocyclic carbene and four equatorial pyridine donors, is readily prepared on a multigram scale. Six coordinate first row transition metal complexes of the general formula [(PY4Im)M(MeCN)](2+) (M = Fe, Co, Ni, Cu), where the PY4Im ligand coordinates in a square pyramidal pentadentate fashion, have been prepared. Structural, spectroscopic, and electrochemical characterization of these compounds provides evidence that PY4Im is a strongly donating ligand that favors the formation of low-spin complexes. Chemical oxidation of the iron(II) complex provides a low spin iron(III) complex, which has also been structurally and spectroscopically characterized. In the case of manganese(II), the PY4Im ligand is unable to either enforce a low-spin state or fully accommodate the metal ion. Rather, the ligand binds in a tridentate, face-capping mode. PMID- 21028849 TI - pH-Sensitive ionomeric particles obtained via chemical conjugation of silk with poly(amino acid)s. AB - Silk-fibroin-based biomaterials have been widely utilized for a range of biomaterial-related systems. For all these previously reported systems, the beta sheet forming feature of the silk was the key stabilizing element of the final material structure. Herein, we describe a different strategy, based on the engineering of silk-based ionomers that can yield stable colloidal composites or particle suspensions through electrostatic interactions. These silk-based ionomers were obtained by carbodiimide-mediated coupling of silk fibroin with polylysine hydrobromide and polyglutamic acid sodium salts, respectively. Colloidal composites could be obtained by mixing the ionomeric pair at high concentration (i.e., 25% w/v), while combining them at lower concentrations (i.e., 5% w/v) yielded particle suspensions. The assembly of the ionomers was driven by electrostatic interactions, pH-dependent, and reversible. The network assembly appeared to be polarized, with the interacting poly(amino acid) chains clustered to the core of the particles and the silk backbone oriented outward. In agreement with this assembly mode, doxorubicin, a hydrophilic antitumor drug, could be released at a slow rate, in a pH-dependent manner, indicating that the inside of the ionomeric particles was mainly hydrophilic in nature. PMID- 21028850 TI - The assembly-inducing laulimalide/peloruside a binding site on tubulin: molecular modeling and biochemical studies with [3H]peloruside A. AB - We used synthetic peloruside A for the commercial preparation of [3H]peloruside A. The radiolabeled compound bound to preformed tubulin polymer in amounts stoichiometric with the polymer's tubulin content, with an apparent K(d) value of 0.35 MUM. A less active peloruside A analogue, (11-R)-peloruside A and laulimalide acted as competitive inhibitors of the binding of the [3H]peloruside A, with apparent K(i) values of 9.3 and 0.25 MUM, respectively. Paclitaxel, epothilone B, and discodermolide had essentially no ability to inhibit [3H]peloruside A binding, confirming that these compounds bind to a different site on tubulin polymer. We modeled both laulimalide and peloruside A into the binding site on beta-tubulin that was identified by Huzil et al. (J. Mol. Biol. 2008, 378, 1016-1030), but our model provides a more reasonable structural basis for the protein-ligand interaction. There is a more complete desolvation of the peloruside A ligand and a greater array of favorable hydrophobic and electrostatic interactions exhibited by peloruside A at its beta-tubulin binding site. In addition, the protein architecture in our peloruside A binding model was suitable for binding laulimalide. With the generation of both laulimalide and peloruside A binding models, it was possible to delineate the structural basis for the greater activity of laulimalide relative to peloruside A and to rationalize the known structure-activity relationship data for both compounds. PMID- 21028853 TI - Responsive core-shell latex particles as colloidosome microcapsule membranes. AB - Responsive core-shell latex particles are used to prepare colloidosome microcapsules using thermal annealing and internal cross linking of the shell, allowing the production of the microcapsules at high concentrations. The core shell particles are composed of a polystyrene core and a shell of poly[2 (dimethylamino)ethyl methacrylate]-b-poly[methyl methacrylate] (PDMA-b-PMMA) chains adsorbed onto the core surface, providing steric stabilization. The PDMA component of the adsorbed polymer shell confers thermally responsive and pH responsive characteristics to the latex particle, and it also provides glass transitions at temperatures lower than those of the core and reactive amine groups. These features facilitate the formation of stable Pickering emulsion droplets and the immobilization of the latex particle monolayer on these droplets to form colloidosome microcapsules. The immobilization is achieved through thermal annealing or cross linking of the shell under mild conditions feasible for large-scale economic production. We demonstrate here that it is possible to anneal the particle monolayer on the emulsion drop surface at 75-86 degrees C by using the lower glass-transition temperature of the shell compared to that of the polystyrene cores (~108 degrees C). The colloidosome microcapsules that are formed have a rigid membrane basically composed of a densely packed monolayer of particles. Chemical cross linking has also been successfully achieved by confining a cross linker within the disperse droplet. This approach leads to the formation of single-layered stimulus-responsive soft colloidosome membranes and provides the advantage of working at very high emulsion concentrations because interdroplet cross linking is thus avoided. The porosity and mechanical strength of the microcapsules are also discussed here in terms of the observed structure of the latex particle monolayers forming the capsule membrane. PMID- 21028852 TI - Solution self-assembly and adsorption at the air-water interface of the monorhamnose and dirhamnose rhamnolipids and their mixtures. AB - The self-assembly in solution and adsorption at the air-water interface, measured by small-angle neutron scattering, SANS, and neutron reflectivity, NR, of the monorhamnose and dirhamnose rhamnolipids (R1, R2) and their mixtures, are discussed. The production of the deuterium-labeled rhamnolipids (required for the NR studies) from a Pseudomonas aeruginosa culture and their separation into the pure R1 and R2 components is described. At the air-water interface, R1 and R2 exhibit Langmuir-like adsorption isotherms, with saturated area/molecule values of about 60 and 75 A(2), respectively. In R1/R2 mixtures, there is a strong partitioning of R1 to the surface and R2 competes less favorably because of the steric or packing constraints of the larger R2 dirhamnose headgroup. In dilute solution (<20 mM), R1 and R2 form small globular micelles, L(1), with aggregation numbers of about 50 and 30, respectively. At higher solution concentrations, R1 has a predominantly planar structure, L(alpha) (unilamellar, ULV, or bilamellar, BLV, vesicles) whereas R2 remains globular, with an aggregation number that increases with increasing surfactant concentration. For R1/R2 mixtures, solutions rich in R2 are predominantly micellar whereas solutions rich in R1 have a more planar structure. At an intermediate composition (60 to 80 mol % R1), there are mixed L(alpha)/L(1) and L(1)/L(alpha) regions. However, the higher preferred curvature associated with R2 tends to dominate the mixed R1/R2 microstructure and its associated phase behavior. PMID- 21028851 TI - Regulation of benzo[a]pyrene-mediated DNA- and glutathione-adduct formation by 2,3,7,8-tetrachlorodibenzo-p-dioxin in human lung cells. AB - Environmental carcinogens, such as polycyclic aromatic hydrocarbons (PAHs), require metabolic activation to DNA-reactive metabolites in order to exert their tumorigenic effects. Benzo[a]pyrene (B[a]P), a prototypic PAH, is metabolized by cytochrome P450 (P450) 1A1/1B1 and epoxide hydrolase to (-)-B[a]P-7,8-dihydro-7,8 diol (B[a]P-7,8-dihydrodiol). B[a]P-7,8-dihydrodiol then undergoes further P4501A1/1B1-mediated metabolism to the ultimate carcinogen, (+)-anti-7,8 dihydroxy-9,10-epoxy-7,8,9,10-tetrahydro-B[a]P (B[a]PDE), which forms DNA-adducts primarily with 2'-deoxyguanosine (dGuo) to form (+)-anti-trans-B[a]PDE-N(2)-dGuo (B[a]PDE-dGuo) in DNA. Pretreatment of cells with 2,3,7,8-tetrachlorodibenzo-p dioxin (TCDD) is known to induce P4501A1/1B1 mRNA expression through the aryl hydrocarbon receptor (AhR) pathway. This causes increased B[a]PDE-dGuo formation in liver cells. In contrast, TCDD induction of H358 lung cells surprisingly caused a decrease in (-)-B[a]P-7,8-dihydrodiol-mediated (+)-B[a]PDE-dGuo adduct formation when compared with the non-TCDD-induced cells. Furthermore, treatment of the TCDD-induced cells with (+/-)-B[a]PDE also resulted in decreased (+) B[a]PDE-dGuo adduct formation when compared with the non-TCDD-induced cells. These data suggested that it was a detoxification pathway that had been up regulated rather than an activation pathway that had been down-regulated. LC-MS was used to analyze B[a]PDE-dGuo and B[a]PDE-GSH-adducts in H358 lung and HepG2 liver cells. There was a significant increase in the (-)-B[a]PDE-GSH-adduct with high enantiomeric excess after treatment of the TCDD-induced H358 cells with (+/ )-B[a]PDE when compared with the noninduced cells. This could explain why increased activation of (-)-B[a]P-7,8-dihydrodiol through TCDD up-regulation of P4501A1/1B1 did not lead to increased (+)-B[a]PDE-dGuo adducts in the H358 lung cells. In addition, TCDD did not induce B[a]PDE-GSH-adduct formation in HepG2 liver cells. (+/-)-B[a]PDE-GSH-adducts were formed at much lower levels in both TCDD-induced and noninduced HepG2 cells when compared with (-)-B[a]PDE-GSH adducts in the H358 lung cells. Therefore, our study has revealed that there is a subtle balance between activation and detoxification of B[a]P in lung-derived compared with liver-derived cells and that this determines how much DNA damage occurs. PMID- 21028854 TI - Light-controlled directional liquid drop movement on TiO2 nanorods-based nanocomposite photopatterns. AB - Patterned polymeric coatings enriched with colloidal TiO(2) nanorods and prepared by photopolymerization are found to exhibit a remarkable increase in their water wettability when irradiated with UV laser light. The effect can be completely reversed using successive storage in vacuum and dark ambient environment. By exploiting the enhancement of the nanocomposites hydrophilicity upon UV irradiation, we prepare wettability gradients along the surfaces by irradiating adjacent surface areas with increasing time. The gradients are carefully designed to achieve directional movement of water drops along them, taking into account the hysteresis effect that opposes the movement as well as the change in the shape of the drop during its motion. The accomplishment of surface paths for liquid flow, along which the hydrophilicity gradually increases, opens the way to a vast number of potential applications in microfluidics. PMID- 21028855 TI - Layer-by-layer surface modification of functional nanoparticles for dispersion in organic solvents. AB - In order to prepare SiO(2) nanoparticles that are dispersible in various organic solvents, an anionic surfactant 1, which branches into a hydrophobic chain and a hydrophilic chain, was adsorbed on to SiO(2) nanoparticles through a layer-by layer surface modification route using polyethyleneimine (PEI). First, the relationship among the additive content of PEI, adsorbed content of PEI, and the redispersion stability of the SiO(2) nanoparticles in water was investigated. While almost the entire PEI was adsorbed when the additive PEI content was lower than 67 mg/g of SiO(2), the adsorbed content of PEI became saturated when the additive content was increased above 90 mg/g of SiO(2). SiO(2) nanoparticles that were saturated with PEI could be redispersed into water at sizes close to their primary particle size without the large-scale formation of aggregates. Next, the anionic surfactant 1 was adsorbed on the SiO(2) nanoparticles by using a SiO(2) aqueous suspension saturated with adsorbed PEI. It was found that the adsorbed content of 1 increased almost linearly as the additive content was increased when the additive condition was below 1400 mg/g of SiO(2). Furthermore, SiO(2) nanoparticles adsorbed with 80 mg/g of SiO(2) of PEI and 810 mg/g of SiO(2) of 1 could be dispersed into various organic solvents with different polarities. This layer-by-layer modification technique can also be applied to Ag nanoparticles in order to prepare Ag nanoparticles that can be dispersed in various organic solvents. PMID- 21028856 TI - Morphological manipulation of ionic block copolymer micelles using an electric field. AB - We present an electric-field-triggered sphere-to-cylinder transition of negatively charged block copolymer micelles with a radically low electric field of 30 V/cm. The system investigated is dilute solutions of strong polyelectrolyte containing ionic-b-neutral block copolymers (i.e., poly(styrenesulfonate-b methylbutylene)). We have carried out in situ small-angle X-ray scattering experiments equipped with a dc power supply, combined with electron microscopy and atomic force microscopy. The application of small electrical fields across the solutions of spherical micelles results in the transient morphology of interconnected spheres, which are eventually transformed into a cylindrical shape with time. The E-field-induced cylindrical micelles revert to spherical micelles when the E field is switched off. PMID- 21028857 TI - Conformational diversity of short DNA duplex. AB - Two 25 base-pair cDNA strands are encapsulated within an optically trapped nanodroplet, and we observe the kinetics of their hybridization in dynamic equilibrium via single-molecule fluorescence resonance energy transfer (FRET) as a function of temperature and of the solution's NaCl concentration. We have observed the duplex unfolding and refolding, and we have observed quasistable partially unfolded states under low salinity conditions. Furthermore, our measurements reveal that, even in conditions under which the duplex is stable, it undergoes conformational fluctuations in solution. PMID- 21028858 TI - Interfacial properties of emulsions stabilized with surfactant and nonsurfactant coated boehmite nanoparticles. AB - The properties of emulsions stabilized with surface-modified boehmite particles of 26 and 8 nm in diameter have been investigated. The surface-modified particles were prepared by mixing aqueous dispersions of cationic boehmite particles with aqueous solutions of the surfactant p-dodecylbenzenesulfonic acid (DBSA) or the nonsurfactant p-toluenesulfonic acid (TSA). For the 26 nm particles, interfacial tension measurements indicate that p-dodecylbenzenesulfonic acid partitions between the particle surface and the oil-water interface, while p-toluenesulfonic acid remains on the particle surface. The partitioning of p dodecylbenzenesulfonic acid supports the formation of emulsions, although in the absence of the particles the same surfactant concentration is not sufficient for emulsion stabilization. Due to the fast exchange kinetics, p dodecylbenzenesulfonic acid is gradually replaced by particles. At equilibrium, the interfacial tension in the presence of the surface-modified particles is between the values for the pure particles and the pure surfactant solutions. However, the interfacial tension is independent of the surfactant concentration used in the preparation of the particles. Reducing the particle size to 8 nm leads to increased emulsion stability, and thus, the minimum particle concentration required to prepare stable emulsions was reduced to 0.1 g/L. However, above approximately 3.5 mmol/L of the sulfonic acids, the small particles dissolve slowly, and the emulsion stability is lost. This mechanism can be used to trigger the collapse of the emulsions. PMID- 21028860 TI - Effect of perfluoroalkyl chain length on proton conduction in fluoroalkylated phosphonic, phosphinic, and sulfonic acids. AB - The effects of increasing perfluoroalkyl chain length on the molecular properties of viscosity, diffusivity, and ionic conductivity of a series of acid model compounds analogous to comb-branch perfluorinated ionomers functionalized with phosphonic, phosphinic, and sulfonic protogenic groups are reported. Anhydrous proton transport by a Grotthuss-like hopping mechanism was observed to occur efficiently in phosphorus-based fluoroalkylated model acids but only when there is a relatively low perfluoroalkyl content. The decrease in degree of dissociation of the protogenic groups follows the order phosphonic > phosphinic > sulfonic, and the degree of dissociation and the magnitude of ion-ion correlations are approximately independent of chain length. PMID- 21028859 TI - Toward an alternative intrinsic probe for spectroscopic characterization of a protein. AB - The intrinsic fluorescent amino acid tryptophan is the unanimous choice for the spectroscopic investigation of proteins. However, several complicacies in the interpretation of tryptophan fluorescence in a protein are inevitable and an alternative intrinsic protein probe is a longstanding demand. In this contribution, we report an electron-transfer reaction in a human transporter protein (HSA) cavity which causes the tryptophan residue (Trp214) to undergo chemical modification to form one of its metabolites kynurenine (Kyn214). Structural integrity upon modification of the native protein is confirmed by dynamic light scattering (DLS) as well as near and far circular dichroism (CD) spectroscopy. Femtosecond-resolved fluorescence transients of the modified protein describe the dynamics of solvent molecules in the protein cavity in both the native and denatured states. In order to establish general use of the probe, we have studied the dipolar interaction of Kyn214 with a surface-bound ligand (crystal violet, CV) of the protein. By using the sensitivity of FRET, we have determined the distance between Kyn214 (donor) and CV (acceptor). Our study is an attempt to explore an alternative intrinsic fluorescence probe for the spectroscopic investigation of a protein. In order to establish the efficacy of the modification technique we have converted the tryptophan residues of other proteins (bovine serum albumin, chymotrypsin and subtilisin Carlsberg) to kynurenine and confirmed their structural integrity. We have also shown that catalytic activity of the enzymes remains intact upon the modification. PMID- 21028861 TI - Glycosidic-bond hydrolysis mechanism catalyzed by cellulase Cel7A from Trichoderma reesei: a comprehensive theoretical study by performing MD, QM, and QM/MM calculations. AB - Cellulase Cel7A from Trichoderma reesei is one of the most abundant and effective cellulases. Structural studies have established that Cel7A is a retaining glycosidase and it can processively hydrolyze cellobiose units from the reducing end of a cellulose chain. Here, to elucidate the mechanism of enzymatic catalysis of cellulase Cel7A, we carried out a multisized level theoretical study by performing MD, QM, and QM/MM calculations. At the accurate level of theory, we showed the mechanism details of the catalytic cycle, which involves the configuration inversion of the anomeric center twice: the first results in the glycosidic bond cleavage and the formation of covalent glycosyl-enzyme intermediate, and the second restores the anomeric carbon to its original configuration. Calculated results have provided detailed structural and energetic information about these two processes, both of which proceed according to a S(N)2 type-like mechanism via loose transition state structures. It is clearly indicated that the glycosidic bond hydrolysis involves the formation of a covalent glycosyl-enzyme intermediate, which has been identified as the minimum on the potential energy surface. At the catalytic active region, hydrogen bond interactions exist throughout the whole process of the catalytic cycle, which are of special importance for stabilizing the glycosyl-enzyme intermediate. The present results provide a clear paradigm of the mechanisms of general glycosidases, which hydrolyze the glycosidic bonds with net retention of the anomeric configuration. PMID- 21028862 TI - Stability of perpendicular and parallel lamellae within lamellae of multiblock terpolymers. AB - The phase behaviors of multiblock terpolymer A(BC)(n)B (or A(BC)(n)) with equal volume fractions of A and compositional symmetric (BC)(n)B (or (BC)(n)) are investigated by using the pseudospectral method of the self-consistent mean field theory. These terpolymers can self-assemble into hierarchical lamellar phases of perpendicular or parallel lamellae within lamellae, and the number of B/C thin layers in the parallel phase can be varied. The relative stability among these hierarchical lamellar phases can be tuned by the three interaction parameters of chi(AB)N, chi(AC)N, and chi(BC)N. Two-dimensional phase diagrams, the cross sections of the three-dimensional phase diagram, are determined in our calculations. Our conclusion that the perpendicular phase is stable only in the case of chi(AC)N ? chi(AB)N < chi(BC)N is consistent with experimental observations by Bates's group. In addition, our results suggest that the existence of the perpendicular phase is generic in both types of terpolymers: A(BC)(n)B and A(BC)(n), with different values of n, even for the special case of A(BC)(n), that is, an ABC linear terpolymer. PMID- 21028863 TI - 1H hyperfine interactions in the Mn-cluster of photosystem II in the S2 state detected by hyperfine sublevel correlation spectroscopy. AB - A study of the hydrogen hyperfine couplings of the Mn-cluster of the oxygen evolving complex of Photosystem II in the S(2) state of the Kok cycle by means of hyperfine sublevel correlation spectroscopy was achieved. Features corresponding to hyperfine interaction of at least two hydrogen nuclei were detected. Combining our results with previous ENDOR data, hyperfine constants were determined, and by using a model for the structure and electronic spin state of the Mn-cluster, relevant structural information of the S(2) state was obtained. This new information can be used for improving our knowledge about the structure and function of the Mn-cluster during light-driven water oxidation reaction in oxygenic photosynthetic organisms. PMID- 21028864 TI - Molecular weight dependence of LB morphology of poly(n-hexyl isocyanate) (PHIC). AB - The morphologies of Langmuir-Blodgett (LB) films of two fractionated poly(n-hexyl isocyanate) (PHIC) and those of their binary mixtures were observed by AFM, together with those of an unfractionated PHIC. The low molecular weight PHIC formed random packing of bundles consisting of rigid rods, while the high molecular weight PHIC formed random packing of bundles consisting of hairy rods. Bundle interpenetration was observed only for the latter in the semidilute regime. In the bilayer region, the area occupied by the PHIC bundles in the upper layer was obviously smaller for the high molecular weight PHIC than for the low molecular weight PHIC, suggesting that the bundles of high molecular weight PHIC more easily interpenetrate than those of low molecular weight PHIC. For the blended films composed of both low and high molecular weight PHICs, the characteristic morphologies of the respective PHIC samples were no longer present. Moreover, the morphologies of the blended films appeared to resemble each other at any molar fraction owing to the ideal miscibility of the low molecular weight and high molecular weight PHICs. The morphologies of the blended films were also similar to that of the unfractionated PHIC film in the dilute regime. In the semidilute regime, the blended films became rounded owing to an increase in bundles interpenetration between PHICs as compared to that in the dilute regime, whereas the morphology of unfractionated PHIC films remained unchanged as compared to that in the dilute regime. PMID- 21028865 TI - Surface initiated atom transfer radical polymerization: access to three dimensional wavelike polymer structure modified capillary columns for online phosphopeptide enrichment. AB - Reversible phosphorylation is one of the most important post-translational modifications of proteins and a key regulator of cellular signaling pathways. Specific enrichment of phosphopeptides from proteolytic digests is a prerequisite for large scale identification of protein phosphorylation by mass spectrometry. Online enrichment of phosphopeptides attracts particular interests due to its automated operation, higher throughput and reproducibility, lower sample loss, and contamination. Here, we report a new type of capillary column developed using surface initiated atom transfer radical polymerization (SI-ATRP) for automated online phosphopeptide enrichment. SI-ATRP modification leads to a surface confined growth of three-dimensional wavelike polymer structure on the inner wall of capillary columns and, therefore, results in largely increased surface area. Furthermore, the noncross-linked flexible polymer chains grown by SI-ATRP create a large internal volume that allows phosphopeptides to penetrate into during enrichment and also facilitate the interaction between the numerous functional groups in the polymer chains and target phosphopeptides. Therefore, highly efficient and specific enrichment is achieved even for a low femtomole of phosphopeptides. The loading capacity is increased more than an order of magnitude compared with that obtained using conventional open tubular capillary columns. The SI-ATRP modified capillary column was successful applied in the online phosphoproteomics analysis of HepG2 cell lysate and resulted in 10 times improved phosphopeptide identification than the previously reported number. Finally, the SI-ATRP technique is compatible with a variety of functional monomers, and therefore, versatile potential applications in reverse phase, ion exchange, and affinity chromatography can be expected. PMID- 21028866 TI - Designing molecular switches based on DNA-base mispairing. AB - Stabilization of unstable mispairs on protonation in a DNA sequence can result in a change in the sequence conformation. Such sequences are being actively used for the synthesis of pH-driven molecular switches that have applications in biological pH sensing. We have studied various conformations of different mispairs of bases and their protonated forms using density functional theory (DFT) at B3LYP/6-31+G(d) and M05-2X/6-31+G(d,p) levels. Both gas-phase and aqueous-phase calculations are reported. Solvent phase calculations were done using the PCM and the COSMO solvation model. Our results show that the criterion for the protonation of a particular base in a mispair is not just its higher proton affinity. The planarity of the structure is significantly important, and a planar structure is energetically preferred over a bent mispair. Our calculations also show that the stabilization gained through protonation for the A-C, A-G, and the C-C mispairs is substantial (~20.0 kcal/mol); therefore, these are good candidates for pH-driven molecular switches. PMID- 21028867 TI - Visualization of dynamic conformational switching of the G-quadruplex in a DNA nanostructure. AB - We herein report the real-time observation of G-quadruplex formation by monitoring the G-quadruplex-induced global change of two duplexes incorporated in a DNA nanoscaffold. The introduced G-rich strands formed an interstrand (3 + 1) G quadruplex structure in the presence of K(+), and the formed four-stranded structure was disrupted by removal of K(+). These conformational changes were visualized in a nanoscaffold in real-time with fast-scanning atomic force microscopy. PMID- 21028868 TI - Palladium-catalyzed cyclization of propargylic compounds. AB - Many groups have explored the scope of the palladium-based cyclization of propargylic compounds since Tsuji's first report in 1985. Through the proper positioning of an internal nucleophilic center and the judicious selection of an appropriate external nucleophile, the synthetic chemist can effectively assert control over the course of the reaction and its products. However, initial investigations were very limited: only heterocyclic compounds were originally synthesized. We have found the palladium-catalyzed cyclization of propargylic compounds to be a very efficient method for producing both carbocyclic and heterocyclic compounds. In this Account, we discuss the cyclization reactions of functionalized propargylic compounds with a variety of nucleophiles that we have developed over the past few years. We also review similar reactions reported by other groups. We focus here on the cyclization of functionalized propargylic compounds containing a carbon nucleophilic center that is in close proximity to the propargylic moiety. We conducted a detailed investigation of their cyclizations with carbon nucleophiles, with nitrogen nucleophiles, with oxygen nucleophiles, and without nucleophiles. We have developed several efficient and useful methods for the synthesis of indenes, naphthalenes, polycycles, and spirocyclic compounds. All of these reactions proceed satisfactorily under very mild conditions; high regio- and stereoselectivity have been observed as well. In the course of our studies, we provided the first demonstration of a novel tandem C-H activation/bis-cyclization reaction of propargylic compounds with terminal alkynes. In addition, we used external nucleophiles to investigate the cyclization of functionalized propargylic compounds that bear an unsaturated carbon-carbon or carbon-heteroatom bond. We presented the first report of the use of external nucleophiles to initiate a novel cyclization of functionalized propargylic compounds containing an electrophile. This revelation provided a fresh perspective through the discovery of a new type of domino cyclization of propargylic compounds. Metal-catalyzed cyclization of propargylic compounds can provide indenes, cyclopentanones, cyclic carbonates, benzofurans, and a range of other cyclic molecules. A thorough understanding of the mechanisms involved in this class of reaction affords exceptional synthetic control, as shown here by our development of efficient procedures and reagents for palladium-catalyzed propargylic cyclizations. PMID- 21028869 TI - Gemcitabine causes minimal modulation of carboplatin-DNA monoadduct formation and repair in bladder cancer cells. AB - We are developing a method to identify cellular resistance to carboplatin by using accelerator mass spectrometry to measure carboplatin-DNA adducts formed from drug microdoses (~1/100th the therapeutic dose). Such an approach would be particularly useful if it is still valid in combination chemotherapy. We examined whether the addition of gemcitabine, another chemotherapeutic drug, could influence carboplatin-DNA adduct levels. There were no substantial differences in the levels of carboplatin-DNA adducts in cells upon exposure to the carboplatin/gemcitabine combination at various doses and schedules. These data demonstrate that microdosing is feasible for the characterization of carboplatin resistance when given in combination with gemcitabine. PMID- 21028870 TI - Polycyano derivatives of some organic tri- and hexacyclic molecules are powerful super- and hyperacids in the gas phase and DMSO: computational study by DFT approach. AB - B3LYP/6-311+G(2df,p)//B3LYP/6-31+G(d) calculations convincingly show that tricyclic organic compounds 1 and 2 offer scaffolds suitable for tailoring powerful neutral organic acids. Their cyanation at all C(sp(2))-H positions provide superacids as evidenced by their enthalpies of deprotonation DeltaHacid(1bCN) = 257.2 and DeltaHacid(2bCN) = 250.9 kcal mol(-1), which are close to the threshold of hyperacidity of 245 kcal mol(-1). On the other hand hexacyclic system 3 cyanated at all possible substitution sites along the perimeter except the acidic C(sp(3))-H position provides a true hyperacid with DeltaHacid(3aCN) = 242.8 kcal mol(-1). The reason behind the dramatic acidifying effect is a vigorous anionic resonance effect in the corresponding conjugate bases assisted by a cooperative substituent effect of the CN groups. It is convincingly shown that compounds 1 and 2 represent rigid antiaromatic quasi [12]annulene and aromatic quasi-[14]annulene par excellence, respectively, conforming to Huckel's (4n + 2)pi electron count rule in the bridged polycyclic systems. Calculations of the pKa values in DMSO show that the polycyano derivatives are powerful superacids in solutions too. PMID- 21028871 TI - The development and catalytic uses of N-heterocyclic carbene gold complexes. AB - Gold has emerged as a powerful synthetic tool in the chemist's arsenal. From the early use of inorganic salts such as AuCl and AuCl(3) as catalysts, the field has evolved to explore ligands that fine-tune reactivity, stability, and, more recently, selectivity in gold-mediated processes. Substrates generally contain alkenes or alkynes, and they usually involve straightforward protocols in air with solvents that can often times be of technical grade. The actual catalytic species is the putative cationic gold(I) complex [Au(L)](+) (where L is a phosphorus-based species or N-heterocyclic carbene, NHC). The early gold systems bearing phosphine and phosphite ligands provided important transformations and served as useful mechanistic probes. More recently, the use of NHCs as ligands for gold has rapidly gained in popularity. These two-electron donor ligands combine strong sigma-donating properties with a steric profile that allows for both stabilization of the metal center and enhancement of its catalytic activity. As a result, the gold-NHC complexes have been used as well-defined precatalysts and have permitted the isolation of reactive single-component systems that are now used instead of the initial [Au(L)Cl]/silver salt method. Because some are now commercially available, NHC-containing gold(I) complexes are gathering increasing interest. In this Account, we describe the chronological development of this chemistry in our laboratories, highlighting the advantages of this family of gold complexes and reviewing their synthesis and applications in catalysis. We first outline the syntheses, which are straightforward. The complexes generally exhibit high stability, allowing for indefinite storage and easy handling. We next consider catalysis, particularly examining efficacy in cycloisomerization, other skeletal rearrangements, addition of water to alkynes and nitriles, and C-H bond activation. These processes are quite atom-economical, and in the most recent C-H reactions the only byproduct is water. State-of-the-art methodology now involves single-component catalysts, precluding the need for costly silver co catalysts. Remarkably, the use of an NHC as a supporting ligand has permitted the isolation of [Au(L)(S)](+) species (where S is a solvent molecule such as a nitrile), which can act as single-component catalysts. Some improvements are still needed, as the single components are most often synthesized with a silver reagent. Owing to the stabilizing effect of NHC coordination, some NHC-containing systems can catalyze extremely challenging reactions (at temperatures as high as 140 degrees C) and react at very low loadings of gold (ppm levels). Our latest developments deal with C-H bond functionalization and hold great promise. We close with a selection of important developments by the community with gold-NHC complexes. As demonstrated by the turns and twists encountered during our own journey in the gold-NHC venture, the chemistry described here, combining fundamental organometallic, catalytic, and organic methodology, remains rich in opportunities, especially considering that only a handful of gold(I) architectures has been studied. We hope this Account will encourage young researchers to explore this emerging area, as the adage "the more you do, the more you have to do" surely holds true in gold-mediated catalysis. PMID- 21028872 TI - Hydration structure of the quaternary ammonium cations. AB - Two indicators of the hydropathicity of small solutes are introduced and tested by molecular dynamics simulations. These indicators are defined as probabilities of the orientation of water molecules' dipoles and hydrogen bond vectors, conditional on a generalized distance from the solute suitable for arbitrarily shaped molecules. Using conditional probabilities, it is possible to distinguish features of the distributions in close proximity of the solute. These regions contain the most significant information on the hydration structure but cannot be adequately represented by using, as is usually done, joint distance-angle probability densities. Our calculations show that using our indicators a relative hydropathicity scale for the interesting test set of the quaternary ammonium cations can be roughly determined. PMID- 21028873 TI - Study of the interaction of pancreatic lipase with procyanidins by optical and enzymatic methods. AB - The interactions between porcine pancreatic lipase (PL) and grape seed procyanidins were studied by an enzymatic assay, fluorescence quenching, nephelometry, and dynamic light scattering (DLS). An inhibitory effect of grape seed procyanidins on lipase hydrolytic activity was found. Both the inhibition of lipase activity by procyanidins and the respective quenching of intrinsic protein fluorescence increased with the average degree of polymerization of the tested procyanidins. The association between procyanidins and enzyme involves a specific interaction as inferred from the fluorescence assays despite not changing significantly the tertiary structure of the protein. For all tested procyanidins it was shown, both by DLS and by nephelometry, that an increase in aggregation occurs up to a stoichiometric maximum after which further procyanidin addition causes a decrease in aggregation of aggregates. The maximum size of aggregates was shown to be closely related to the maximum overall aggregation. It was also shown that the inhibition of enzyme activity is to a large extent independent of the formation of aggregates. PMID- 21028874 TI - Specificity of non-Michaelis-Menten enzymes: necessary information for analyzing metabolic pathways. AB - The specificity of an enzyme obeying the Michaelis-Menten equation is normally measured by comparing the kcat/Km for different substrates, but this is inappropriate for enzymes with a Hill coefficient h different from 1. The obvious alternative of generalizing Km in the expression as K0.5, the substrate concentration for half-saturation, is better, but it is not entirely satisfactory either, and here we show that kcat/K0.5(h) gives satisfactory results for analyzing the kinetic behavior of metabolic pathways. The importance of using kcat/K0.5(h) increases with the value of h, but even when h is small, it makes an appreciable difference, as illustrated for the mammalian hexokinases. Reinterpretation of data for the specificity of these enzymes in terms of the proposed definition indicates that hexokinase D, often believed highly specific for glucose, and accordingly called "glucokinase", actually has the lowest preference for glucose over fructose of the four isoenzymes found in mammals. PMID- 21028875 TI - Attenuation of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced gap junctional intercellular communication (GJIC) inhibition in MCF-10A cells by c9,t11 conjugated linoleic acid. AB - The protective effect of c9,t11-conjugated linoleic acid (CLA) on the inhibition of gap junctional intercellular communication (GJIC) was examined in a human mammary epithelial cell line (MCF-10A) treated with 12-O-tetradecanoylphorbol-13 acetate (TPA), relative to t10,c12-CLA isomer. TPA inhibited GJIC in a dose dependent and reversible manner and was associated with connexin 43 phosphorylation. Pretreatment of 20 MUM c9,t11-CLA for 24 h prior to 60 nM TPA for 1 h prevented the inhibition of GJIC by reducing the phosphorylation of connexin 43 via suppressing extracellular signal-regulated kinases (ERK1/2) activation. Reactive oxygen species (ROS) accumulation by TPA was attenuated by c9,t11-CLA. The efficacy of c9,t11-CLA in protecting inhibition of GJIC, connexin 43 phosphorylation, and ROS production was superior to that of t10,c12-CLA. These results suggest that c9,t11-CLA, including t10,c12-CLA, prevents the carcinogenesis of MCF-10A cells by protecting down-regulation of GJIC during the cancer promotion stage, and lack of their toxicities could be an excellent indicator for the chemoprevention of breast cancer. PMID- 21028876 TI - Detection of T-T mismatches using mass spectrometry: specific interactions of Hg(II) with oligonucleotides rich in thymine (T). AB - Electrospray ionization tandem mass spectrometry (ESI-MS/MS) was employed in a detailed study of the interactions of mercury dications with selected oligodeoxynucleotides rich and poor in thymine (T): d(5'-TT-3'), d(5'-TTT-3'), d(5'-TTTT-3'), d(5'-GG-3'), d(5'-CC-3'), d(5'-AA-3'), d(5'-GCTTGC-3'), d(5' GTGCTC-3'), d(5'-GCATGC-3'), and d(5'-GCGCGC-3'). Specific interactions are observed for Hg(2+) with pure and mixed thymine sequences in which simultaneous bonding between two thymine units is indicated, and this is consistent with a model proposed in the literature in which Hg(2+) covalently coordinates to two thymines by replacing two N3 imino protons of the bases. The ESI-MS/MS measurements, combined with data on the thermal stability of mixed sequence hexadeoxynucleotides, indicate that mercury prefers thymines over the other binding sites in oligonucleotides both in solution and in the gas phase. These results point toward the effective use of Hg(2+) in the fast detection of mismatch base pairs incorporated in oligonucleotide duplexes and longer mixed DNA sequences using ESI-MS/MS. PMID- 21028877 TI - Substituent and solvent effects on electronic structure and spectral property of ReCl(CO)3(N?N) (N?N = glyoxime): DFT and TDDFT theoretical studies. AB - The ground- and excited-state structures of five Re(I) halide glyoxime complexes ReCl(CO)(3)(N(?)N) (N(?)N = glyoxime (DHG 1), dimethylglyoxime (DMG 2), cyclohexane dione glyoxime (CHDG 3), dibromoglyoxime (DBG 4), and dimethylformylgloxime (DMFG 5)) have been studied with density functional theory (DFT) and configuration interaction with single excitations (CIS) methods. Time dependent density functional theory/polarized continuum model (TDDFT/PCM) was carried out to predict the absorption and emission spectra in different media. The effect of substituent and solvent has been researched. It is found that electron-donating groups increase the lowest unoccupied molecular orbital (LUMO) energy resulting in the increased highest occupied molecular orbital (HOMO)-LUMO energy gap. The change leads to their absorption spectra blue shifts in the order 1 > 2 > 3, which arises from the HOMO-1 -> LUMO. Just the opposite, electron withdrawing groups lead to the spectra red shifts (5 > 4 > 1) because of the decreased HOMO-LUMO energy gap. The reorganization energy (lambda) calculations show that the relatively balanceable charges transfer abilities of 2 will result in the higher efficiency of organic light emitting devices (OLEDs). In addition, both the absorption and the emission spectra display red shifts in different extents with the decrease of solvent polarity. PMID- 21028878 TI - Tuning the optical characteristics of poly(p-phenylenevinylene) by in situ au nanoparticle generation. AB - A composite of 1,4-dihexyloxy-poly(p-phenylenevinylene) (DHPPV) and gold nanoparticles (AuNPs) was prepared by an efficient and simple in situ method. The formation of DHPPV-AuNP composites was confirmed through high-resolution transmission electron microscopy (TEM); UV/vis absorption spectra showed a large blue shift in the polymer absorption peak, which was greater than 60 nm in solution, accompanied by a remarkable change in the intensity, whereas the photoluminescence (PL) spectra in the solution showed only a marginal decrease in intensity in the presence of AuNPs. Solid-state UV/vis spectra of DHPPV-AuNP also showed a decrease in the intensity of the shoulder peak in the region of 400-450 nm. Interesting features were observed in the solid-state PL spectra, where the efficient energy transfer from AuNP to DHPPV results in the complete disappearance of the 585 nm peak with a dominant peak appearing at 635 nm. TEM analysis confirmed that AuNPs were embedded in the DHPPV matrix systematically, thus presenting a simple tool to assemble hybrid nanowires comprising pi conjugated organic/polymeric systems and inorganic nanoparticles with likely applications in nanosized optoelectronic devices. The optical properties of DHPPV AuNP could be further tuned by treating the composite with octadecane thiol or sodium sulfide, resulting in a further blue shift of 65 nm. PMID- 21028879 TI - Conformational and thermodynamic properties of gaseous levulinic acid. AB - Molecular modeling is used to determine low-energy conformational structures and thermodynamic properties of levulinic acid in the gas phase. Structure and IR vibrational frequencies are obtained using density functional and Moller-Plesset perturbation theories. Electronic energies are computed using G3//B3LYP and CBS QB3 model chemistries. Computed anharmonic frequencies are consistent with reported experimental data. Population analysis shows a boat- and a chainlike structure to be most abundant at 298 K, with increasing proportions of two other conformers at higher temperatures. Population mean distribution values for thermodynamic quantities are derived. At 298 K and 1 atm, the enthalpy of formation, entropy, and heat capacity are -613.1 +/- 1.0 kJ.mol(-1), 407.4 J.mol( 1).K(-1), and 132.3 J.mol(-1).K(-1), respectively. PMID- 21028880 TI - The bridged binding mode as a new, versatile template for the selective activation of carbon-fluorine bonds in fluoroolefins: activation of trifluoroethylene. AB - We report the selective activation of carbon-fluorine bonds in trifluoroethylene using the diiridium complex [Ir(2)(CH(3))(CO)(2)(dppm)(2)][OTf] (1). Coordination of trifluoroethylene in a bridging position between the two metals in 1 results in facile fluoride ion loss in three different ways. Attack by strong fluorophiles such as Me(3)SiOTf and HOTf results in F(-) removal from one of the geminal fluorines to give the cis-difluorovinyl-bridged product [Ir(2)(CH(3))(OTf)(CO)(2)(MU-kappa(1):eta(2)-C(F)?CFH)(dppm)(2)][OTf]. A second activation can also be accomplished by addition of excess Me(3)SiOTf to give the fluorovinylidene-bridged product [Ir(2)(CH(3))(OTf)(CO)(2)(MU C(2)FH)(dppm)(2)][OTf](2). Interestingly, activation of the trifluoroethylene bridged precursor by water also occurs, yielding [Ir(2)(CH(3))(CO)(2)(kappa(1) C(H)?CF(2))(MU-OH)(dppm)(2)][OTf], in which the lone vicinal fluorine is removed, leaving a geminal arrangement of fluorines in the product. A [1,2]-fluoride shift can also be induced in the trifluoroethylene-bridged precursor upon the addition of CO to give the 2,2,2-trifluoroethylidene-bridged product [Ir(2)(CH(3))(CO)(3)(MU-C(H)CF(3))(dppm)(2)][CF(3)SO(3)]. Addition of hydrogen to the cis-difluorovinyl-bridged product results in the quantitative elimination of cis-difluoroethylene, while its reaction with CO yields a mixture of cis difluoropropene and 2,3-difluoropropene by reductive elimination of the methyl and difluorovinyl groups with an accompanying isomerization in the case of the second product. Finally, protonation of the 2,2,2-trifluoroethylidene-bridged product liberates 1,1,1-trifluoroethane, in which one hydrogen (H(+)) is from the acid while the other hydrogen (H(-)) is derived from activation of the methyl group. PMID- 21028881 TI - GC-MS metabolomic analysis reveals significant alterations in cerebellar metabolic physiology in a mouse model of adult onset hypothyroidism. AB - Although adult-onset hypothyroidism (AOH) has been connected to neural activity alterations, including movement, behavioral, and mental dysfunctions, the underlying changes in brain metabolic physiology have not been investigated in a systemic and systematic way. The current knowledge remains fragmented, referring to different experimental setups and recovered from various brain regions. In this study, we developed and applied a gas chromatography-mass spectrometry (GC MS) metabolomics protocol to obtain a holistic view of the cerebellar metabolic physiology in a Balb/cJ mouse model of prolonged adult-onset hypothyroidism induced by a 64-day treatment with 1% potassium perchlorate in the drinking water of the animals. The high-throughput analysis enabled the correlation between multiple parallel-occurring metabolic phenomena; some have been previously related to AOH, while others implicated new pathways, designating new directions for further research. Specifically, an overall decline in the metabolic activity of the hypothyroid compared to the euthyroid cerebellum was observed, characteristically manifested in energy metabolism, glutamate/glutamine metabolism, osmolytic/antioxidant capacity, and protein/lipid synthesis. These alterations provide strong evidence that the mammalian cerebellum is metabolically responsive to AOH. In light of the cerebellum core functions and its increasingly recognized role in neurocognition, these findings further support the known phenotypic manifestations of AOH into movement and cognitive dysfunctions. PMID- 21028882 TI - Mechanism of enantioselective C-C bond formation with bifunctional chiral ru catalysts: NMR and DFT study. AB - The mechanism of Michael addition reactions of 1,3-dicarbonyl compounds to cyclic enones catalyzed by bifunctional Ru catalysts bearing N-sulfonylated (R,R)-DPEN ligands (DPEN = (R,R)-1,2-diphenylethylenediamine) was studied by NMR and DFT computational analyses. NMR investigation of the stoichiometric reactions of chiral amido Ru complexes, Ru(N-sulfonylated dpen)(eta(6)-arene) 1a-c, with dimethyl malonate 2 and beta-keto ester 3 revealed that at decreased temperatures deprotonation proceeds in a stereoselective manner to provide amine complexes. The reaction with malonic ester 2 provided exclusively C-bound amino Ru complexes 6a,c, while the reaction of beta-keto ester 3 gave an equilibrium mixture of rapidly interconverting C- and O-bound complexes. The structures of C-bound Ru complex 6c and O-bound Ru complex 9c were determined by single crystal X-ray analysis. A computational study showed that the enatioselective C-C bond formation proceeds through intermediate formation of chelating ion pairs that coordinate a molecule of enone via the Ru metal center producing a highly organized environment for the C-C bond formation, yielding selectively only one enantiomer of the product. Systematic study of a series of the catalyst-substrate combinations revealed that the experimentally observed sense of enantioselection was consistently explained by computational analysis. The tendency of increasing ee with the bulk of the coordinated arene in Ru complex is reproduced computationally by changes in the difference of either ZPPE-corrected energies or Gibbs free energies for S- and R-pathways. PMID- 21028883 TI - Pulse Radiolysis Studies of Temperature Dependent Electron Transfers among Redox Centers in ba(3)-Cytochrome c Oxidase from Thermus thermophilus: Comparison of A- and B-Type Enzymes. AB - The functioning of cytochrome c oxidases involves orchestration of long-range electron transfer (ET) events among the four redox active metal centers. We report the temperature dependence of electron transfer from the Cu(A)(r) site to the low-spin heme-(a)b(o) site, i.e., Cu(A)(r) + heme-a(b)(o) -> Cu(A)(o) + heme a(b)(r) in three structurally characterized enzymes: A-type aa(3) from Paracoccus denitrificans (PDB code 3HB3 ) and bovine heart tissue (PDB code 2ZXW ), and the B-type ba(3) from T. thermophilus (PDB codes 1EHK and 1XME ). k,T data sets were obtained with the use of pulse radiolysis as described previously. Semiclassical Marcus theory revealed that lambda varies from 0.74 to 1.1 eV, H(ab), varies from ~2 * 10(-5) eV (0.16 cm(-1)) to ~24 * 10(-5) eV (1.9 cm(-1)), and betaD varies from 9.3 to 13.9. These parameters are consistent with diabatic electron tunneling. The II-Asp111Asn Cu(A) mutation in cytochrome ba(3) had no effect on the rate of this reaction whereas the II-Met160Leu Cu(A)-mutation was slower by an amount corresponding to a decreased driving force of ~0.06 eV. The structures support the presence of a common, electron-conducting "wire" between Cu(A) and heme-a(b). The transfer of an electron from the low-spin heme to the high-spin heme, i.e., heme-a(b)(r) + heme-a(3)(o) -> heme-a(b)(o) + heme-a(3)(r), was not observed with the A-type enzymes in our experiments but was observed with the Thermus ba(3); its Marcus parameters are lambda = 1.5 eV, H(ab) = 26.6 * 10(-5) eV (2.14 cm(-1)), and betaD = 9.35, consistent also with diabatic electron tunneling between the two hemes. The II-Glu15Ala mutation of the K-channel structure, ~24 A between its CA and Fe-a(3), was found to completely block heme b(r) to heme-a(3)(o) electron transfer. A structural mechanism is suggested to explain these observations. PMID- 21028884 TI - Determination of energies and sites of binding of PFOA and PFOS to human serum albumin. AB - Structure and energies of the binding sites of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) to human serum albumin (HSA) were determined through molecular modeling. The calculations consisted of a compound approach based on docking, followed by molecular dynamics simulations and by the estimation of the free binding energies adopting WHAM-umbrella sampling and semiempirical methodologies. The binding sites so determined are common either to known HSA fatty acids sites or to other HSA sites known to bind to pharmaceutical compounds such as warfarin, thyroxine, indole, and benzodiazepin. Among the PFOA binding sites, five have interaction energies in excess of -6 kcal/mol, which become nine for PFOS. The calculated binding free energy of PFOA to the Trp 214 binding site is the highest among the PFOA complexes, -8.0 kcal/mol, in good agreement with literature experimental data. The PFOS binding site with the highest energy, -8.8 kcal/mol, is located near the Trp 214 binding site, thus partially affecting its activity. The maximum number of ligands that can be bound to HSA is 9 for PFOA and 11 for PFOS. The calculated data were adopted to predict the level of complexation of HSA as a function of the concentration of PFOA and PFOS found in human blood for different levels of exposition. The analysis of the factors contributing to the complex binding energy permitted to outline a set of guidelines for the rational design of alternative fluorinated surfactants with a lower bioaccumulation potential. PMID- 21028885 TI - Convergent assembly of the spiroacetal subunit of didemnaketal B. AB - A highly convergent synthesis of the C9-C28 spiroacetal subunit of didemnaketal B has been accomplished. Assembly of the C9-C15 alkylborate and C16-C21 enol phosphate by means of Suzuki-Miyaura coupling and acid-catalyzed cyclization of the derived dihydroxy enol ether enabled a rapid and efficient construction of the spiroacetal subunit. The C22-C28 side chain was incorporated via Nozaki Hiyama-Kishi coupling to complete the synthesis. PMID- 21028886 TI - Local structure in ionic liquids investigated by hyper-Rayleigh scattering. AB - A series of ionic liquids involving imidazolium, pyrrolidinium, and alkyl ammonium cations with different anions (namely, [BF(4)], [PF(6)], [TFSI], [SCN], and [(CN)(2)N]) have been studied by hyper-Rayleigh scattering (HRS), which is a powerful technique to probe the local structure of liquids in a multipolar description. The interpretation of the HRS measurements in terms of an elementary structural (ES) entity has revealed a dominating octopolar nature of ES scatterers. By combining the HRS analysis with density functional theory calculations for different-sized ion pair clusters, we show that the octopolar nature to ES hyperpolarizability in ionic liquids (ILs) originates from a complex local structure due to the formation of 'transient' ion clusters within the time of observation of HRS (~10(-12) to 10(-14) s). We emphasize that such a structural organization puts clearly into evidence the influence of nonadditive interaction processes within first shell of neighbors (<1 nm) leading to a coherent HRS structure factor in ILs. PMID- 21028887 TI - "White graphenes": boron nitride nanoribbons via boron nitride nanotube unwrapping. AB - Inspired by rich physics and functionalities of graphenes, scientists have taken an intensive interest in two-dimensional (2D) crystals of h-BN (analogue of graphite, so-called "white" graphite). Recent calculations have predicted the exciting potentials of BN nanoribbons in spintronics due to tunable magnetic and electrical properties; however no experimental evidence has been provided since fabrication of such ribbons remains a challenge. Here, we show that few- and single-layered BN nanoribbons, mostly terminated with zigzag edges, can be produced under unwrapping multiwalled BN nanotubes through plasma etching. The interesting stepwise unwrapping and intermediate states were observed and analyzed. Opposed to insulating primal tubes, the nanoribbons become semiconducting due to doping-like conducting edge states and vacancy defects, as revealed by structural analyses and ab initio simulations. This study paves the way for BN nanoribbon production and usage as functional semiconductors with a wide range of applications in optoelectronics and spintronics. PMID- 21028888 TI - High capacity capillary electrophoresis-electrospray ionization mass spectrometry: coupling a porous sheathless interface with transient isotachophoresis. AB - A sheathless interface making use of a porous tip has been used for coupling capillary electrophoresis and electrospray ionization mass spectrometry. First, effective flow rates using the interface have been characterized. It was found that the interface is capable of generating a stable spray with flow rates ranging from below 10 nL/min to >340 nL/min, enabling its use in either the mass or concentration-sensitive region of the electrospray process. Subsequently, by analyzing peptide mixtures of increasing complexity, we have demonstrated that this platform provides exquisite sensitivity enabling the detection of very low amounts of materials with very high resolving power. Transient isotachophoresis (t-ITP) can also be integrated with this setup to increase the mass loading of the system while maintaining peak efficiency and resolution. Concentration limits of detection in the subnanomolar or nanomolar range can be achieved with or without t-ITP, respectively. The application of a vacuum at the inlet of the separation capillary further allowed the peak capacity of the system to be improved while also enhancing its efficiency. As a final step in this study, it was demonstrated that the intrinsic properties of the interface allows the use of coated noncharged surfaces so that very high peak capacities can be achieved. PMID- 21028889 TI - Pulicatins A-E, neuroactive thiazoline metabolites from cone snail-associated bacteria. AB - The cone snail Conus pulicarius from the Philippines provides a specific habitat for actinomycetes and other bacteria. A phenotypic screen using primary cultures of mouse dorsal root ganglion neurons revealed that one C. pulicarius associate, Streptomyces sp. CP32, produces a series of natural products that enhance or diminish whole-cell Ca(2+) flux. These compounds include known thiazoline compounds and a series of new derivatives, pulicatins A-E (6-10). Individual compounds were shown to bind to a series of human receptors, with selective binding to the human serotonin 5-HT(2B) receptor. Here, we report the structure elucidation of the new compounds and results of the neurological assays. PMID- 21028890 TI - Benzophenones and biflavonoids from Rheedia edulis. AB - Two new polyisoprenylated benzophenones, 32-hydroxy-ent-guttiferone M (1) and 6 epi-guttiferone J (2), along with seven known compounds, 6-epi-clusianone (3), guttiferone A (4), xanthochymol (5), guttiferone E (6), isoxanthochymol (7), (+) volkensiflavone (8), and (+)-morelloflavone (9), were identified from the seeds and rinds of Rheedia edulis. Compounds 1-3 and 5-9 have been isolated and identified from this species for the first time. The structures of the new compounds were elucidated mainly by analysis of their 1D and 2D NMR spectroscopic data, and their absolute configurations were determined by comparison of their experimental optical rotation and electronic circular dichroism measurements with those values predicted by DFT calculations. Compound 1 showed significant antioxidant activity in both DPPH and ABTS free radical scavenging assays, whereas compound 2 was inactive. PMID- 21028891 TI - Abyssomicin I, a modified polycyclic polyketide from Streptomyces sp. CHI39. AB - Abyssomicin I (1), a new modified polycyclic polyketide, was isolated from the culture extract of a soil-derived Streptomyces sp. The structure of 1 was elucidated by interpretation of NMR and other spectroscopic data. The stereochemistry of the new compound was assigned by NOE analysis, chemical derivatization, and application of the modified Mosher method. While 1 was inactive against bacteria and yeasts, the oxidized derivative 7 showed weak activities against gram-positive bacteria. Compounds 1 and 7 exhibited inhibitory effects on tumor cell invasion with IC(50) values of 11 and 0.21 MUM, respectively. PMID- 21028892 TI - LC-MS/MS analysis of ovarian cancer metastasis-related proteins using a nude mouse model: 14-3-3 zeta as a candidate biomarker. AB - Peritoneal implantation is the most common metastatic pattern of epithelial ovarian cancer, and the five-year survival rate of patients is dramatically decreased when large-scale peritoneal metastasis occurs. This study aimed to determine serum proteins that could be used to detect early peritoneal metastasis of ovarian cancer. The secreted (or shed) proteins of the ovarian cancer cell line SKOV-3 were analyzed using LC-MS/MS, and 97 proteins were identified in the SKOV-3 culture supernatant. After the SKOV-3 cells were xenografted into the peritoneal cavities of nude mice, 3 of the 97 proteins were detected in animal sera. Following enzyme-linked immunosorbent assay (ELISA)-based screening of clinical blood samples, one of the three proteins, 14-3-3 zeta, was identified as a candidate biomarker. The average serum levels of 14-3-3 zeta in patients with epithelial ovarian cancer and benign gynecological diseases were significantly different. The expression of 14-3-3 zeta was associated with the degree of cancer peritoneal metastasis, the emergence of ascites, bilateral involvement, and the clinical stage and substage. Using 14-3-3 zeta, the overall diagnostic accuracy for ovarian cancer was greatly improved. Furthermore, siRNA-based experiments demonstrated that 14-3-3 zeta was responsible for approximately 62, 65, and 30% of the migratory, invasive, and implantation abilities of SKOV-3 cells, respectively. The present results demonstrated that the nude mouse xenograft model is an efficient system for performing function-oriented biomarker discovery, which can be used for a variety of research tasks in future molecular diagnoses, targeted therapies, and ovarian cancer vaccine development. PMID- 21028893 TI - Structures and properties of porous coordination polymers based on lanthanide carboxylate building units. AB - A series of 3-D lanthanide porous coordination polymers, [Ln(6)(BDC)(9)(DMF)(6)(H(2)O)(3).3DMF](n) [Ln = La, 1; Ce, 2; Nd, 3], [Ln(2)(BDC)(3)(DMF)(2)(H(2)O)(2)](n) [Ln = Y, 4; Dy, 5; Eu, 6], [Ln(2)(ADB)(3)(DMSO)(4).6DMSO.8H(2)O](n) [Ln = Ce, 7; Sm, 8; Eu, 9; Gd, 10], {[Ce(3)(ADB)(3)(HADB)(3)].30DMSO.29H(2)O}(n) (11), and [Ce(2)(ADB)(3)(H(2)O)(3)](n) (12) (H(2)BDC = benzene-1,4-dicarboxylic acid and H(2)ADB = 4,4'-azodibenzoic acid), have been synthesized and characterized. In 1 3, the adjacent Ln(III) ions are intraconnected to form 1-D metal-carboxylate oxygen chain-shaped building units, [Ln(4)(CO(2))(12)](n), that constructed a 3-D framework with 4 * 7 A rhombic channels. In 4-6, the dimeric Ln(III) ions are interlinked to yield scaffolds with 3-D interconnecting tunnels. Compounds 7-10 are all 3-D interpenetrating structures with the CaB6-type topology structure. Compound 11 is constructed by ADB spacers and trinulcear Ce nodes with a NaCl type topology structure and a 1.9-nm open channel system. In 12, the adjacent Ce(III) ions are intraconnected to form 1-D metal-carboxylate oxygen chain-shaped building units, [Ln(4)(CO(2))(12)](n), and give rise to a 3-D framework. Moreover, 6 exhibits characteristic red luminescence properties of Eu(III) complexes. The magnetic susceptibilities, over a temperature range of 1.8-300 K, of 3, 6, and 7 have also been investigated; the results show paramagnetic properties. PMID- 21028894 TI - Novel potent orally active multitargeted receptor tyrosine kinase inhibitors: synthesis, structure-activity relationships, and antitumor activities of 2 indolinone derivatives. AB - The inhibition of receptor tyrosine kinases (RTKs) has become a successful approach in the development of anticancer agents. Many potent small-molecule kinase inhibitors have been discovered. We report herein a series of pyrrolo fused-heterocycle-2-indolinone analogues as inhibitors of vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), and c-Kit. Among them, some pyrrolo-fused six- and seven-membered-heterocycle derivatives such as 9, 15, 23, and 25 are potent inhibitors of VEGFR, PDGFR, and c-Kit both enzymatically (<50 nM) and cellularly (<50 nM). Furthermore, compounds 9 and 25 possess favorable pharmacokinetic profiles and demonstrate good efficacies against human HT-29 cell colon tumor xenografts in nude mice. Further evaluations are in progress. PMID- 21028896 TI - Molecular basis of the interaction between proteins of plant origin and proanthocyanidins in a model wine system. AB - Plant proteins are being used as a replacement for animal proteins in wine fining. The surface hydrophobicity of plant proteins in four commercial preparations differing for their origin and processing was assessed by using a fluorescent hydrophobic probe in wine-like media. Displacement of the probe by addition of wine phenolics was measured as a way to compare and predict to some extent the efficiency of these proteins in wine fining. It was found that the binding of polyphenols was much more specific than that of the hydrophobic probe. Further analysis of the polyphenol pattern in protein-treated wine-like solutions pointed out two relevant facts: (1) proteins may interfere with the chemistry of the interactions between polyphenols and other wine components; (2) individual protein preparation having different surface hydrophobicities also have different specificities in binding different polymeric forms of the polyphenols and in their substitution products. These findings are related to the possible carry over of transition metals and may be worth exploring for custom tailoring the fining process. Whether the practical application of the latter finding will call for production and/or screening of plant-derived proteins with features appropriate to this task remains to be investigated. However, the approaches presented in this study may be used for large-scale screening of protein suitability for fining application under laboratory conditions, providing guidelines for their use in actual winemaking applications. PMID- 21028897 TI - Hydration effects on energy relaxation of ferric cytochrome c films after Soret band photoexcitation. AB - Protein hydration plays a critical role in protein dynamics and biological processes. Pump-probe transmission measurement has been applied to investigate the hydration effects on the energy relaxation of a heme protein ferric Cytochrome c (Cyt c) film after soret-band photoexcitation. Transient dynamics study indicates that the energy internal conversion time of ~300 fs is independent of hydration. The vibrationally excited electronic ground-state recovery rates show two transitions at the hydration level of h = 12.4-16.5% and 21.7-23.5%. The first transition occurs at the hydration level for the onset of an increasing ferric Cyt c flexibility while the second transition occurs at the saturated hydration level. The hydration dependence of steady-state electronic absorption spectrum results shows that the Q-band peak is nearly constant in center wavelength, but the line width surprisingly narrows with increasing hydration. For the ~695 nm absorbance associated with the MET80-Fe bond, the intensity increases with increasing hydration and slightly blue shifts. The 695 nm peak grows rapidly at h = 12.4% and then plateaus at h = 21.7%. This research shows that ~695 nm absorbance and ground-state recovery rates are sensitive to the hydration of the protein. This study will aid in understanding how hydration modulates the activity of the protein dynamics at a local level. PMID- 21028895 TI - Multimodal clinical imaging to longitudinally assess a nanomedical anti inflammatory treatment in experimental atherosclerosis. AB - Atherosclerosis is an inflammatory disease causing great morbidity and mortality in the Western world. To increase the anti-inflammatory action and decrease adverse effects of glucocorticoids (PLP), a nanomedicinal liposomal formulation of this drug (L-PLP) was developed and intravenously applied at a dose of 15 mg/kg PLP to a rabbit model of atherosclerosis. Since atherosclerosis is a systemic disease, emerging imaging modalities for assessing atherosclerotic plaque are being developed. (18)F-Fluoro-deoxy-glucose positron emission tomography and dynamic contrast enhanced magnetic resonance imaging, methods commonly used in oncology, were applied to longitudinally assess therapeutic efficacy. Significant anti-inflammatory effects were observed as early as 2 days that lasted up to at least 7 days after administration of a single dose of L-PLP. No significant changes were found for the free PLP treated animals. These findings were corroborated by immunohistochemical analysis of macrophage density in the vessel wall. In conclusion, this study evaluates a powerful two-pronged strategy for efficient treatment of atherosclerosis that includes nanomedical therapy of atherosclerotic plaques and the application of noninvasive and clinically approved imaging techniques to monitor delivery and therapeutic responses. Importantly, we demonstrate unprecedented rapid anti-inflammatory effects in atherosclerotic lesions after the nanomedical therapy. PMID- 21028898 TI - Camphoratins A-J, potent cytotoxic and anti-inflammatory triterpenoids from the fruiting body of Taiwanofungus camphoratus. AB - Ten new triterpenoids, camphoratins A-J (1-10), along with 12 known compounds were isolated from the fruiting body of Taiwanofungus camphoratus. Their structures were established by spectroscopic analysis and chemical methods. Compound 10 is the first example of a naturally occurring ergosteroid with an unusual cis-C/D ring junction. Compounds 2-6 and 11 showed moderate to potent cytotoxicity, with EC(50) values ranging from 0.3 to 3 MUM against KB and KB-VIN human cancer cell lines. Compounds 6, 10, 11, 14-16, 18, and 21 exhibited anti inflammatory NO-production inhibition activity with IC(50) values of less than 5 MUM, and were more potent than the nonspecific NOS inhibitor N(omega)-nitro-L arginine methyl ester. PMID- 21028899 TI - Enantioselective synthesis of (-)-sclerophytin A by a stereoconvergent epoxide hydrolysis. AB - The cytotoxic natural product (-)-sclerophytin A was constructed in 13 steps from geranial. Highlights from the synthesis are a stereoselective Oshima-Utimoto reaction, a Shibata-Baba indium-promoted radical cyclization, and a novel stereoconvergent epoxide hydrolysis. PMID- 21028900 TI - Designing multifunctional expanded pyridiniums: properties of branched and fused head-to-tail bipyridiniums. AB - The multifaceted potentialities of expanded pyridiniums (EPs), based on one pyridinium core bearing a 4-pyridyl or 4-pyridylium as the N-pyridinio group, are established at both experimental and theoretical levels. Two classes of head-to tail (htt) EPs were designed, and their first representative elements were synthesized and fully characterized. The branched (B) family is made up of 2,6 diphenyl-4-aryl-1,4'-bipyridin-1-ium (or 1,1'-diium) species, denoted 1B and 2B for monocationic EPs (with aryl = phenyl and biphenyl, respectively) and 1B(Me) and 2B(Me) for related quaternarized dicationic species. The series of fused (F) analogues comprises 9-aryl-benzo[c]benzo[1,2]quinolizino[3,4,5,6 ija][1,6]naphthyridin-15-ium species, denoted 1F and 2F, and their 2,15-diium derivatives referred to as 1F(Me) and 2F(Me). Electrochemistry (in MeCN vs SCE) reveals that branched EPs undergo a single reversible bielectronic reduction at ca. -0.92 V for 1B/2B and -0.59 V for 1B(Me)/2B(Me), whereas pericondensed species show two reversible monoelectronic reductions at ca. -0.83 and -1.59 V for 1F/2F and ca. -0.42 and -1.07 V for 1F(Me)/2F(Me). Regarding electronic absorption features, all htt-EP chromophores show absorptivity in the range of ca. 1-4 * 10(4) M(-1) cm(-1), with red-edge absorptions extending toward 450 and 500 nm (in MeCN) for 2B(Me) and 2F(Me), respectively. These lowest-energy pi-pi* transitions are ascribed to intramolecular charge transfer between the electron releasing biphenyl group and the htt-bipyridinium electron-withdrawing subsystems. EPs display room-temperature photoemission quantum yields ranging from 10% to 50%, with the exception of 1B, and branched luminophores are characterized by larger Stokes shifts (8000-10 000 cm(-1)) than fused ones. Lastly, a method to predict the efficiency of photobiscyclization of branched EPs into fused ones, based on the analysis of computed difference maps in total electron density for singlet excited states, is proposed. PMID- 21028901 TI - CD and MCD spectroscopic studies of the two Dps miniferritin proteins from Bacillus anthracis: role of O2 and H2O2 substrates in reactivity of the diiron catalytic centers. AB - DNA protection during starvation (Dps) proteins are miniferritins found in bacteria and archaea that provide protection from uncontrolled Fe(II)/O radical chemistry; thus the catalytic sites are targets for antibiotics against pathogens, such as anthrax. Ferritin protein cages synthesize ferric oxymineral from Fe(II) and O(2)/H(2)O(2), which accumulates in the large central cavity; for Dps, H(2)O(2) is the more common Fe(II) oxidant contrasting with eukaryotic maxiferritins that often prefer dioxygen. To better understand the differences in the catalytic sites of maxi- versus miniferritins, we used a combination of NIR circular dichroism (CD), magnetic circular dichroism (MCD), and variable temperature, variable-field MCD (VTVH MCD) to study Fe(II) binding to the catalytic sites of the two Bacillus anthracis miniferritins: one in which two Fe(II) react with O(2) exclusively (Dps1) and a second in which both O(2) or H(2)O(2) can react with two Fe(II) (Dps2). Both result in the formation of iron oxybiomineral. The data show a single 5- or 6-coordinate Fe(II) in the absence of oxidant; Fe(II) binding to Dps2 is 30* more stable than Dps1; and the lower limit of K(D) for binding a second Fe(II), in the absence of oxidant, is 2-3 orders of magnitude weaker than for the binding of the single Fe(II). The data fit an equilibrium model where binding of oxidant facilitates formation of the catalytic site, in sharp contrast to eukaryotic M-ferritins where the binuclear Fe(II) centers are preformed before binding of O(2). The two different binding sequences illustrate the mechanistic range possible for catalytic sites of the family of ferritins. PMID- 21028902 TI - Glycocluster design for improved avidity and selectivity in blocking human lectin/plant toxin binding to glycoproteins and cells. AB - Blocking lectin/toxin binding to human cells by suitable inhibitors can therapeutically protect them from harmful effects. Clustered design of ligand presentation holds the promise of affinity increase relative to the free sugar and inherent selectivity among lectin targets. Using first a solid-phase assay with a glycoprotein presenting N-glycans as lectin-reactive probe, we assessed the inhibitory potency of bi- to tetravalent clusters on a plant toxin and three human adhesion/growth-regulatory lectins. Enhanced avidity relative to the free sugar was detected together with lectin-type selectivity. These effects were confirmed on the level of cells in vitro, also for two leguminous lectins. The lack of toxicity in cell proliferation assays excluded concerns to further work on these compounds. The given cluster design and the strategic combination of the two assay systems of increasing biorelevance will thus be helpful to take the next steps in drug development, e.g. tailoring the sugar headgroup. PMID- 21028903 TI - Specificity of a prodrug-activating enzyme hVACVase: the leaving group effect. AB - Human valacyclovirase (hVACVase) is a prodrug-activating enzyme for amino acid prodrugs including the antiviral drugs valacyclovir and valganciclovir. In hVACVase-catalyzed reactions, the leaving group of the substrate corresponds to the drug moiety of the prodrug, making the leaving group effect essential for the rational design of new prodrugs targeting hVACVase activation. In this study, a series of valine esters, phenylalanine esters, and a valine amide were characterized for the effect of the leaving group on the efficiency of hVACVase mediated prodrug activation. Except for phenylalanine methyl and ethyl esters, all of the ester substrates exhibited a relatively high specificity constant (k(cat)/K(m)), ranging from 850 to 9490 mM(-1).s(-1). The valine amide Val-3-APG exhibited significantly higher K(m) and lower k(cat) values compared to the corresponding ester Val-3-HPG, indicating poor specificity for hVACVase. In conclusion, the substrate leaving group has been shown to affect both binding and specific activity of hVACVase-catalyzed activation. It is proposed that hVACVase is an ideal target for alpha-amino acid ester prodrugs with relatively labile leaving groups while it is relatively inactivate toward amide prodrugs. PMID- 21028904 TI - Solvent-free synthesis of soluble, near-IR absorbing titanyl phthalocyanine derivatives. AB - Solvent-free synthesis of a series of alkylthio-substituted titanyl phthalocyanine (TiOPc) derivatives starting from the corresponding phthalonitriles (Pn) is reported. This methodology eliminates the formation of the unmetalated phthalocyanine (H2Pc), a side product that makes purification difficult. The alkylthio groups on the reported derivatives enhance solubility in common organic solvents and shift the absorption to the near-IR region. PMID- 21028905 TI - Synthesis of 14N- and 15N-labeled trityl-nitroxide biradicals with strong spin spin interaction and improved sensitivity to redox status and oxygen. AB - Simultaneous evaluation of redox status and oxygenation in biological systems is of great importance for the understanding of biological functions. Electron paramagnetic resonance (EPR) spectroscopy coupled with the use of the nitroxide radicals have been an indispensable technique for this application but are still limited by low oxygen sensitivity and low EPR resolution in part due to the moderately broad EPR triplet and spin quenching through bioreduction. In this study, we showed that these drawbacks can be overcome through the use of trityl nitroxide biradicals allowing for the simultaneous measurement of redox status and oxygenation. A new trityl-nitroxide biradical TNN14 composed of a pyrrolidinyl-nitroxide and a trityl and its isotopically labeled (15)N analogue TNN15 were synthesized and characterized. Both biradicals exhibited much stronger spin-spin interaction with J > 400 G compared with that of the previous synthesized trityl-nitroxide biradicals TN1 (~160 G) and TN2 (~52 G) with longer linker chain length. The enhanced stability of TNN14 was evaluated using ascorbate as reductant, and the effect of different types of cyclodextrins on its stability in the presence of ascorbate was also investigated. Both biradicals are sensitive to redox status, and their corresponding trityl-hydroxylamines resulting from the reduction of the biradicals by ascorbate share the same oxygen sensitivity. Of note is that the (15)N-labeled TNN15-H with an EPR doublet exhibits improved EPR signal amplitude as compared with that of TNN14-H with an EPR triplet. In addition, cyclic voltammetric studies verify the characteristic electrochemical behaviors of the trityl-nitroxide biradicals. PMID- 21028907 TI - Photoinduced [4 + 4], [4 + 2], and [2 + 2] cycloadditions of o-quinones with oxazoles: chemo-, regio-, and diastereoselectivity. AB - Photoinduced reactions of the 1,2-dicarbonyl compounds phenanthrenequinone (PQ), 1-acetylisatin (IS), and benzil (BZ) with the oxazoles 1a-j have been investigated. In photoreactions of PQ with the oxazoles, in addition to the 1,4 dioxins derived from [4 + 2] cycloaddition and the oxetanes from the Paterno Buchi [2 + 2] reactions, [4 + 4] cycloaddition products are formed in the reactions with 1a, 1c, 1g, 1i, and 1j, with the quinone's dicarbonyl unit (O?C C?O) and the oxazole's C?N-C?C moiety as two 4pi addends. Photoreactions of IS with the oxazoles 1f and 1g give the [4 + 4] cycloaddition products exclusively, while in photoreactions of IS with 1a, 1c, 1e, 1h, and 1i, [4 + 4] products are formed together with the [2 + 2] products. Reaction pathway partitioning in these photocycloaddtions strongly depends on the substitution pattern on the oxazole ring. The presence of a substituent at the oxazole's C2 atom hampers the [4 + 4] pathway by causing steric hindrance to radical pair recombination in the corresponding 1,7-diradical intermediate to form the [4 + 4] cycloaddition products. A substituent at the C4 atom results in steric hindrance for ring closure of the 1,4-diradicals in the [2 + 2] cycloaddition pathway, therefore favoring the [4 + 4] and [4 + 2] cycloaddition pathways. Regio- and diastereoselectivity in the [2 + 2] and [4 + 4] cycloadditions have been discussed based on the thermodynamic stability of the relevant triplet diradical intermediates and the conformations of these diradicals suitable for the intersystem crossing process. Photoreactions of BZ with the oxazoles afford only [2 + 2] cycloaddition products. PMID- 21028908 TI - Efficient coupling between dielectric-loaded plasmonic and silicon photonic waveguides. AB - The realization of practical on-chip plasmonic devices will require efficient coupling of light into and out of surface plasmon waveguides over short length scales. In this letter, we report on low insertion loss for polymer-on-gold dielectric-loaded plasmonic waveguides end-coupled to silicon-on-insulator waveguides with a coupling efficiency of 79 +/- 2% per transition at telecommunication wavelengths. Propagation loss is determined independently of insertion loss by measuring the transmission through plasmonic waveguides of varying length, and we find a characteristic surface-plasmon propagation length of 51 +/- 4 MUm at a free-space wavelength of lambda = 1550 nm. We also demonstrate efficient coupling to whispering-gallery modes in plasmonic ring resonators with an average bending-loss-limited quality factor of 180 +/- 8. PMID- 21028909 TI - Large-diameter graphene nanotubes synthesized using Ni nanowire templates. AB - We report a method to synthesize tubular graphene structures by chemical vapor deposition (CVD) on Ni nanowire templates, using ethylene as a precursor at growth temperature of around 750 degrees C. Unlike carbon nanotubes that are synthesized via conventional routes, the number of graphene layers is determined by the growth time and is independent of the tube diameter and tube length, which follow those of the nanowire template. This allows us to realize large-diameter tubes with shells comprising a few or many layers of graphene as desired. Thin graphene layers are observed to be highly crystalline, and of uniform thickness throughout the length of the nanowire. Raman analysis shows the presence of a small level of defects typical of CVD-grown graphene. The metallic core could be removed by chemical etching to result in a collapsed tube. Backgated field-effect transistor measurements were conducted on the collapsed graphene tube. This approach to the realization of tubular graphene offers new opportunities for graphene-based nanodevices. PMID- 21028906 TI - Allele-selective inhibition of mutant huntingtin expression with antisense oligonucleotides targeting the expanded CAG repeat. AB - Huntington's disease (HD) is a currently incurable neurodegenerative disease caused by the expansion of a CAG trinucleotide repeat within the huntingtin (HTT) gene. Therapeutic approaches include selectively inhibiting the expression of the mutated HTT allele while conserving function of the normal allele. We have evaluated a series of antisense oligonucleotides (ASOs) targeted to the expanded CAG repeat within HTT mRNA for their ability to selectively inhibit expression of mutant HTT protein. Several ASOs incorporating a variety of modifications, including bridged nucleic acids and phosphorothioate internucleotide linkages, exhibited allele-selective silencing in patient-derived fibroblasts. Allele selective ASOs did not affect the expression of other CAG repeat-containing genes and selectivity was observed in cell lines containing minimal CAG repeat lengths representative of most HD patients. Allele-selective ASOs left HTT mRNA intact and did not support ribonuclease H activity in vitro. We observed cooperative binding of multiple ASO molecules to CAG repeat-containing HTT mRNA transcripts in vitro. These results are consistent with a mechanism involving inhibition at the level of translation. ASOs targeted to the CAG repeat of HTT provide a starting point for the development of oligonucleotide-based therapeutics that can inhibit gene expression with allelic discrimination in patients with HD. PMID- 21028910 TI - Bis(MU-oxo) dicopper(III) species of the simplest peralkylated diamine: enhanced reactivity toward exogenous substrates. AB - N,N,N',N'-tetramethylethylenediamine (TMED), the simplest and most extensively used peralkylated diamine ligand, is conspicuously absent from those known to form a bis(MU-oxo)dicopper(III) (O) species, [(TMED)(2)Cu(III)(2)(MU(2) O)(2)](2+), upon oxygenation of its Cu(I) complex. Presented here is the characterization of this O species and its reactivity toward exogenous substrates. Its formation is complicated both by the instability of the [(TMED)Cu(I)](1+) precursor and by competitive formation of a presumed mixed valent trinuclear [(TMED)(3)Cu(III)Cu(II)(2)(MU(3)-O)(2)](3+) (T) species. Under most reaction conditions, the T species dominates, yet, the O species can be formed preferentially (>80%) upon oxygenation of acetone solutions, if the copper concentration is low (<2 mM) and [(TMED)Cu(I)](1+) is prepared immediately before use. The experimental data of this simplest O species provide a benchmark by which to evaluate density functional theory (DFT) computational methods for geometry optimization and spectroscopic predictions. The enhanced thermal stability of [(TMED)(2)Cu(III)(2)(MU(2)-O)(2)](2+) and its limited steric demands compared to other O species allows more efficient oxidation of exogenous substrates, including benzyl alcohol to benzaldehyde (80% yield), highlighting the importance of ligand structure to not only enhance the oxidant stability but also maintain accessibility to the nascent metal/O(2) oxidant. PMID- 21028911 TI - Gold-catalyzed oxidative coupling reactions with aryltrimethylsilanes. AB - During continuing studies with a novel oxidative gold oxyarylation reaction, arylsilanes were found to be competent coupling partners, providing further evidence for an intramolecular electrophilic aromatic substitution mechanism. While providing yields complementary to those of the previously described boronic acid methods, the use of trimethylsilanes reduces the observation of homocoupling byproducts and allows for facile intramolecular coupling reactions. PMID- 21028912 TI - Mass spectrometric analysis of synapsins in Drosophila melanogaster and identification of novel phosphorylation sites. AB - Synapsins are synaptic vesicle-associated phosphoproteins that play a major role in the fine regulation of neurotransmitter release. In Drosophila, synapsins are required for complex behavior including learning and memory. Synapsin isoforms were immunoprecipitated from homogenates of wild-type Drosophila heads using monoclonal antibody 3C11. Synapsin null mutants (Syn(97)) served as negative controls. The eluted proteins were separated by SDS-PAGE and visualized by silver staining. Gel pieces picked from five bands specific for wild type were analyzed by nano-LC-ESI-MS/MS following multienzyme digestion (trypsin, chymotrypsin, AspN, subtilisin, pepsin, and proteinase K). The protein was unambiguously identified with high sequence coverage (90.83%). A number of sequence conflicts were observed and the N-terminal amino acid was identified as methionine rather than leucine expected from the cDNA sequence. Several peptides from the larger isoform demonstrated that the in-frame UAG stop codon at position 582 which separates two large open reading frames is read through by tRNAs for lysine. Seven novel phosphorylation sites in Drosophila synapsin were identified at Thr 86, Ser-87, Ser-464, Thr-466, Ser-538, Ser-961, and Tyr-982 and verified by phosphatase treatment. No phosphorylation was observed at the conserved PKA/CaM kinase-I/IV site (RRFS, edited to RGFS) in domain A or a potential PKA site near domain E. PMID- 21028914 TI - New antimicrobial strategies in cystic fibrosis. AB - With more antibiotic resistance and emerging pathogens in cystic fibrosis (CF) patients, the need for new strategies in the lifelong treatment of pulmonary infection has increased. Most of the focus is on chronic infection with Pseudomonas aeruginosa, which is still thought to be the main pathogen leading to advanced CF lung disease. Other bacterial species are also recognized in the pathogenesis of CF lung disease, even though their definitive role is not well established yet. Clearly, expansion of treatment options is urgently needed. This article focuses on recent developments in the field of new antimicrobial strategies for CF. It is clear that studies on new classes of antibiotics or antimicrobial-like drugs are scarce, and that most studies involve new (inhalation) formulations, new routes of delivery, or analogs of existing classes of antibiotics. Studies of new antibiotic-like drugs are, in most cases, in preclinical phases of development and only a few of these agents may reach the market. Importantly, new inhaled antibiotics, e.g. aztreonam, levofloxacin, and fosfomycin, and new, more efficient delivery systems such as dry powder inhalation and liposomes for current antibiotics are in the clinical phase of development. These developments will be of great importance in improving effective treatment and reducing the treatment burden for CF patients in the near future. PMID- 21028915 TI - Pain management in newborns: from prevention to treatment. AB - All neonates in the Neonatal Intensive Care Unit (NICU) or during the first days of life undergo painful and stressful procedures. Epidemiologic studies have shown that pain induced by these procedures is not effectively prevented or is inadequately treated. Pain experienced during the neonatal period may lead to negative outcomes, especially in preterm neonates. Prevention is the first step of pain management, and practical guidelines should be used in the NICU. Assessment must be done with adequate tools that take into account the infant's pathology and gestational age. Distinguishing between acute and prolonged pain is important for both assessment and treatment. The most common drugs that have been studied for the treatment of pain and stress are opioids, hypnosedatives, and NMDA receptor antagonists. Morphine and fentanyl are most frequently used for acute or prolonged pain in the NICU. They have potent analgesic effects and few immediate or long-term adverse effects. Midazolam is a commonly used hypnosedative, but its adverse effects limit its use. Drugs such as propofol and ketamine have been used for acute painful procedures; however, further research is needed to assess their long-term effects. Use of non-pharmacologic pain management techniques has increased in recent years. These methods are easy, inexpensive, and effective in helping newborns recover from painful procedures. Sweet solutions and non-nutritive sucking, breastfeeding, skin-to-skin mother care, swaddling, and facilitated tucking are the most commonly employed and evaluated non-pharmacologic methods. Hospitals should promote and improve parent involvement in pain management. In-service education and well organized hospital teams are crucial for successful implementation of pain protocols in newborns. PMID- 21028916 TI - Tumor necrosis factor inhibitors in the management of juvenile idiopathic arthritis: an evidence-based review. AB - Juvenile idiopathic arthritis (JIA) is a chronic inflammatory disorder of unknown origin that is often treated with a variety of disease-modifying agents. Tumor necrosis factor (TNF) inhibitors are a group of genetically engineered biologic agents that target the proinflammatory cytokine TNF. This review focuses on the use of TNF inhibitors in JIA. Etanercept was the first TNF inhibitor approved for use in children with moderate to severe polyarticular-course JIA following encouraging results from a randomized, double-blind, placebo-controlled, multicenter trial in children. Open-label extension studies of the original trial involving 8 years of follow-up demonstrated the long-term safety and efficacy of etanercept in children. Other studies from established registries also corroborate the safety of etanercept in JIA. The second TNF inhibitor to be approved for use in JIA is adalimumab following recent favorable results from another randomized, placebo-controlled, multicenter study in polyarticular-course JIA. While infliximab is not approved by the US FDA for use in JIA, it is frequently used in clinical practice for this indication. However, because the chimeric structure of infliximab incorporates murine components, it has the potential for allergic and infusion reactions. Patient responses to individual TNF inhibitors may vary depending on concomitant medications such as methotrexate, and also on the category of JIA. PMID- 21028917 TI - The use of triptans for pediatric migraines. AB - Migraine headaches frequently occur in the pediatric population, with a prevalence of 3% in children 2-7 years of age, 4-11% in children 7-11 years of age, and 8-23% in children 11 years of age and older. Migraine without aura is more than twice as common as migraine with aura in children. Headaches are the third leading cause of emergency room referrals and rank in the top five health problems of children. The 2004 American Academy of Neurology's treatment parameter for migraine in children and adolescents recommended that nasal sumatriptan be considered for acute treatment; however, data were lacking to make a decision regarding the available oral triptans at that time. The more recently released European guidelines discuss three different triptans for use in children but no specific triptan was recommended. Currently, six of the seven available triptans have been studied for efficacy and safety in the pediatric population; however, only a few well controlled clinical studies have been conducted. Sumatriptan has the most available data on outcomes in general, with nasal sumatriptan showing the most positive results. Nasal sumatriptan is approved in children older than 12 years of age in Europe. Oral sumatriptan does not show any clinical benefit versus placebo in children. Rizatriptan and zolmitriptan have conflicting efficacy and safety data, with most studies favoring the use of oral rizatriptan and nasal zolmitriptan. Almotriptan is the first triptan to obtain a US FDA indication in adolescents with migraines lasting 4 or more hours. This approval was based upon two studies, one large clinical trial and one very small, open-label, pilot study. At this time, there are insufficient data to recommend naratriptan and eletriptan for first- or second-line use in pediatric patients with migraines. There are currently no efficacy data for frovatriptan in pediatric patients, which limits its use in this population. Adverse effects of triptans and pharmacokinetic data in children and adolescents are similar to those in adults. The triptan class should be considered as an acute treatment option for children and adolescents with migraines, although their use is mostly 'off-label'. Of the available triptans, there are more positive efficacy data for sumatriptan and zolmitriptan nasal sprays, and rizatriptan and almotriptan tablets than for the other triptans. PMID- 21028918 TI - Strategies to prevent cellular rejection in pediatric heart transplant recipients. AB - Despite more than 40 years' experience in pediatric heart transplantation, cellular rejection remains a significant cause of morbidity and mortality. In this review, strategies and agents to prevent acute cellular rejection are discussed. Strategies to prevent rejection are divided into two phases - induction and maintenance therapies. Currently, the most commonly used induction agents are polyclonal antibodies (rabbit or equine antithymocyte globulin) and interleukin-2 receptor antibodies (daclizumab or basiliximab). Induction therapies have reduced early rejection, are renal sparing, and can reduce corticosteroid exposure, but have not yet been shown to have a longer term survival benefit. Multiple maintenance immunosuppressants are available. Nearly all regimens include a calcineurin inhibitor (either ciclosporin [cyclosporine] or tacrolimus). Most combinations in pediatric heart transplantation include an antiproliferative agent (azathioprine, mycophenolate mofetil or, less commonly, sirolimus). Everolimus has seen increasing use in adult heart transplant patients in Europe but, to date, its use is rare in pediatric heart transplantation. The use of corticosteroids as a third agent is still common, but strategies to avoid or minimize their use are increasing. The 'best' combination of therapies varies between studies. By gaining a better understanding of individuals' genetic and environmental risk factors, we may in the future be able to better predict the course of cardiac allografts and enhance our ability to tailor immunosuppression to individual patient variables with the ultimate goal of inducing a state of immune tolerance. PMID- 21028919 TI - Ondansetron dosing in pediatric gastroenteritis: a prospective cohort, dose response study. AB - BACKGROUND: Ondansetron is increasingly used to prevent emesis in children with acute gastroenteritis; however, the optimal dose is unknown. OBJECTIVE: To determine if higher doses of oral ondansetron are associated with greater efficacy or side effects. METHODS: We analyzed data from a prospective clinical trial performed between January 2004 and April 2005. Data were collected on 105 children with dehydration due to gastroenteritis who received an ondansetron oral disintegrating formulation. The following outcomes of efficacy were analyzed: number of vomiting episodes, volume of oral rehydration fluids consumed, percent weight gain, and the proportions of children who had ongoing vomiting, received intravenous rehydration, and were hospitalized. In addition, the number of episodes of diarrhea was evaluated to measure whether there were dose-dependent side effects. RESULTS: Participants were aged 0.5-8.2 years and the dose ranged between 0.13 and 0.26 mg/kg. There was no significant association between the dose of ondansetron and the outcomes of number of vomiting episodes, volume of fluids consumed, increase in bodyweight, or number of diarrhea episodes/hour. The mean dose of ondansetron (mg/kg) administered was not different amongst those who did and did not have ongoing vomiting, undergo hospitalization, and receive intravenous rehydration. CONCLUSIONS: Within the dose range of 0.13-0.26 mg/kg, higher doses of ondansetron were not superior to lower doses, nor were they associated with increased side effects. Thus, ondansetron in this dose range was shown to result in a similar reduction in emesis in children with acute gastroenteritis. PMID- 21028920 TI - Pharmacokinetics of deferiprone in patients with beta-thalassaemia: impact of splenectomy and iron status. AB - BACKGROUND AND OBJECTIVE: Iron-rich transfusions and/or a compensatory increase in iron absorption ultimately result in iron loading in patients with beta thalassaemia. Hence, without iron chelation, iron accumulates relentlessly. Deferiprone has been shown to be capable of reducing the iron burden in patients with beta-thalassaemia. However, there is wide interpatient variation in deferiprone-induced urinary iron excretion (UIE). We hypothesized that splenectomy and iron status might influence the pharmacokinetic profiles of deferiprone in patients with beta-thalassaemia/haemoglobin E, and the present study was aimed at examining this hypothesis. STUDY PARTICIPANTS AND METHODS: Thirty-one patients with beta-thalassaemia/haemoglobin E (20 splenectomized and 11 non-splenectomized patients) were enrolled in the study. After an overnight fast, the subjects received a single oral dose of deferiprone 25 mg/kg of bodyweight. Blood samples were collected pre-dosing and at 15, 30, 45, 60, 90, 120, 180, 240, 300, 360 and 480 minutes after dosing. Urine output was pooled and collected at 0-2, 2-4, 4-8, 8-12 and 12-24 hour intervals. Serum and urine concentrations of deferiprone and its metabolite deferiprone glucuronide were determined using a validated high-performance liquid chromatography method. Serum deferiprone-chelated iron and UIE were determined using a validated colourimetric method. RESULTS: No significant difference in the pharmacokinetic parameters of non-conjugated deferiprone was observed between splenectomized and non splenectomized patients. However, the maximum serum concentration (C(max)) and the area under the serum concentration-time curve (AUC) from time zero to infinity (AUC(infinity)) values of deferiprone glucuronide were significantly lower (both p < 0.05) in splenectomized patients (median 53.2 MUmol/L and 12 634 MUmol * min/L, respectively) than in non-splenectomized patients (median 70.5 MUmol/L and 20 601 MUmol * min/L, respectively). The C(max) and the AUC from time zero to the time of the last measurable concentration (AUC(last)) values of serum deferiprone-chelated iron, as well as UIE, were significantly higher (p < 0.001) in splenectomized patients (median values 7.1 MUmol/L, 1645 MUmol * min/L and 77.1 MUmol, respectively) than in non-splenectomized patients (median values 3.1 MUmol/L, 545 MUmol * min/L and 12.5 MUmol, respectively). Urinary excretion of non-conjugated deferiprone and deferiprone glucuronide did not differ between the two groups. Further analyses using multiple linear regressions indicated that the iron profiles (non-transferrin-bound iron and ferritin) were significant predictors of the pharmacokinetic parameters of non-conjugated deferiprone, deferiprone-chelated iron and UIE. In addition, splenectomy status was identified as the strongest predictor of the AUC(last) of deferiprone-chelated iron and UIE. CONCLUSION: Both iron and splenectomy status have significant effects on the pharmacokinetics and iron chelation efficacy of deferiprone. A greater degree of iron overload in splenectomized patients results in alterations in pharmacokinetic parameters (the C(max) and AUC) of deferiprone glucuronide and deferiprone-chelated iron, as well as a significant increase in UIE. PMID- 21028921 TI - Simple model of the transduction of cell-penetrating peptides. AB - Cell-penetrating peptides (CPPs) such as HIV's trans-activating transcriptional activator (TAT) and polyarginine rapidly pass through the plasma membranes of mammalian cells by an unknown mechanism called transduction. They may be medically useful when fused to well-chosen chains of fewer than about 35 amino acids. The author offers a simple model of transduction in which phosphatidylserines and CPPs effectively form two plates of a capacitor with a voltage sufficient to cause the formation of transient pores (electroporation). The model is consistent with experimental data on the transduction of oligoarginine into mouse C(2)C(12) myoblasts and makes three testable predictions. [Includes supplementary material]. PMID- 21028922 TI - Quantitative statistical description of integrin clusters in adherent cells. AB - Regulation of protein-protein interactions because of their spatial organisation in cells often shapes cell signalling responses to external stimuli, yet most current cell signalling models do not include spatial segregation of proteins beyond coarse control volumes like the cytosol or nucleus. A significant hindrance to spatial modelling of cell signalling is a lack of data describing the spatial organisation of proteins in cells. One signalling system in which spatial organisation is critical is integrin signalling, where protein interactions are restricted to small, micron-sized protein complexes that form on clusters of transmembrane integrin proteins. Using confocal microscopy and image analysis to quantify the size, shape and location of integrin clusters, the authors observed that cells exhibit large variability in these integrin cluster properties. To describe these heterogeneous populations of clusters quantitatively, the authors identified appropriate probability models to characterise the size, shape and location of integrin clusters in a population of adherent cells. The authors determined that integrin cluster sizes are lognormally distributed, integrin cluster eccentricities are beta distributed, and the distances of integrin clusters from the cell centre are gamma distributed. The authors estimated the parameters corresponding to these probability models from empirical data describing integrin clusters in a population of cells, and the resulting probability models describe the heterogeneous populations of clusters. These population models provide the means to create an accurate mathematical description of spatially localised integrin signalling compartments for use in computational models of integrin signalling. PMID- 21028923 TI - Integrating BioPAX pathway knowledge with SBML models. AB - Online databases store thousands of molecular interactions and pathways, and numerous modelling software tools provide users with an interface to create and simulate mathematical models of such interactions. However, the two most widespread used standards for storing pathway data (biological pathway exchange; BioPAX) and for exchanging mathematical models of pathways (systems biology markup language; SBML) are structurally and semantically different. Conversion between formats (making data present in one format available in another format) based on simple one-to-one mappings may lead to loss or distortion of data, is difficult to automate, and often impractical and/or erroneous. This seriously limits the integration of knowledge data and models. In this paper we introduce an approach for such integration based on a bridging format that we named systems biology pathway exchange (SBPAX) alluding to SBML and BioPAX. It facilitates conversion between data in different formats by a combination of one-to-one mappings to and from SBPAX and operations within the SBPAX data. The concept of SBPAX is to provide a flexible description expanding around essential pathway data - basically the common subset of all formats describing processes, the substances participating in these processes and their locations. SBPAX can act as a repository for molecular interaction data from a variety of sources in different formats, and the information about their relative relationships, thus providing a platform for converting between formats and documenting assumptions used during conversion, gluing (identifying related elements across different formats) and merging (creating a coherent set of data from multiple sources) data. PMID- 21028924 TI - Sensitivity analysis predicts that the ERK-pMEK interaction regulates ERK nuclear translocation. AB - Following phosphorylation, nuclear translocation of the mitogen-activated protein kinases (MAPKs), ERK1 and ERK2, is critical for both gene expression and DNA replication induced by growth factors. ERK nuclear translocation has therefore been studied extensively, but many details remain unresolved, including whether or not ERK dimerisation is required for translocation. Here, we simulate ERK nuclear translocation with a compartmental computational model that includes systematic sensitivity analysis. The governing ordinary differential equations are solved with the backward differentiation formula and decoupled direct methods. To better understand the regulation of ERK nuclear translocation, we use this model in conjunction with a previously published model of the ERK pathway that does not include an ERK dimer species and with experimental measurements of nuclear translocation of wild-type ERK and a mutant form, ERK1-4, which is unable to dimerise. Sensitivity analysis reveals that the delayed nuclear uptake of ERK1 4 compared to that of wild-type ERK1 can be explained by the altered interaction of ERK1-4 with phosphorylated MEK (MAPK/ERK kinase), and so may be independent of dimerisation. Our study also identifies biological experiments that can verify this explanation. PMID- 21028925 TI - Exploring mechanisms of oscillations in p53 and nuclear factor-B systems. AB - A number of regulatory networks have the potential to generate sustained oscillations of irregular amplitude, but well conserved period. Single-cell experiments revealed that in p53 and nuclear factor (NF)-B systems the oscillation period is homogenous in cell populations, insensitive to the strength of the stimulation, and is not influenced by the overexpression of p53 or NF-B transcription factors. We propose a novel computational method of validation of molecular pathways models, based on the analysis of sensitivity of the oscillation period to the particular gene(s) copy number and the level of stimulation. Using this method, the authors demonstrate that existing p53 models, in which oscillations are borne at a saddle-node-on-invariant-circle or subcritical Hopf bifurcations (characteristic for systems with interlinked positive and negative feedbacks), are highly sensitive to gene copy number. Hence, these models cannot explain existing experiments. Analysing NF-B system, the authors show the importance of saturation in transcription of the NF-B inhibitor IB. Models without saturation predict that the oscillation period is a rapidly growing function of total NF-B level, which is in disagreement with experiments. The study supports the hypothesis that oscillations of robust period are based on supercritical Hopf bifurcation, characteristic for dynamical systems involving negative feedback and time delay. We hypothesise that in the p53 system, the role of positive feedback is not sustaining oscillations, but terminating them in severely damaged cells in which the apoptotic programme should be initiated. PMID- 21028926 TI - Crosstalk between p53 and nuclear factor-B systems: pro- and anti-apoptotic functions of NF-B. AB - Nuclear factors p53 and NF-B control many physiological processes including cell cycle arrest, DNA repair, apoptosis, death, innate and adaptive immune responses, and inflammation. There are numerous pathways linking these systems and there is a bulk of evidence for cooperation as well as for antagonisms between p53 and NF B. In this theoretical study, the authors use earlier models of p53 and NF-B systems and construct a crosstalk model of p53-NF-B network in order to explore the consequences of the two-way coupling, in which NF-B upregulates the transcription of p53, whereas in turn p53 attenuates transcription of NF-B inhibitors IB and A20. We consider a number of protocols in which cells are stimulated by tumour necrosis factor- (TNF) (that activates NF-B pathway) and/or gamma irradiation (that activates p53 pathway). The authors demonstrate that NF-B may have both anti- and pro-apoptotic roles. TNF stimulation, preceding DNA damaging irradiation, makes cells more resistant to irradiation-induced apoptosis, whereas the same TNF stimulation, when preceded by irradiation, increases the apoptotic cell fraction. The finding suggests that diverse roles of NF-B in apoptosis and cancer could be related to the dynamical context of activation of p53 and NF-B pathways. [Includes supplementary material]. PMID- 21028927 TI - Evolution of gene auto-regulation in the presence of noise. AB - Auto-regulatory negative feedback loops, where the protein expressed from a gene inhibits its own expression are common gene network motifs within cells. We investigate when will introducing a negative feedback mechanism be beneficial in terms of increasing a fitness function that is given by the probability of maintaining protein numbers above a critical threshold. Our results show the existence of a trade-off as introducing feedback decreases the average number of protein molecules driving this number closer to the critical threshold (which decreases fitness) but also reduces stochastic fluctuations around the mean (which increases fitness). We provide analytical conditions under which a negative feedback mechanism can evolve, that is, introducing feedback will increase the above fitness. Analyses of these conditions show that negative feedbacks are more likely to evolve when (i) the source of noise in the protein population is extrinsic (i.e. noise is caused by fluctuations in exogenous signals driving the gene network) and not intrinsic (i.e. the randomness associated with mRNA/protein expression and degradation); (ii) the dynamics of the exogenous signal causing extrinsic noise is slower than the protein dynamics; and (iii) the critical threshold level for the protein number is low. We also show that mRNA/protein degradation rates are critical factors in determining whether transcription or translational negative feedback should evolve. In particular, when the mRNA half-life is much shorter than the protein's half-life, then a transcriptional negative feedback mechanism is more likely to evolve. On the other hand, a translational negative feedback mechanism is preferred with more stable mRNAs that have long half-lifes. PMID- 21028929 TI - Interampatteness - a generic property of biochemical networks. AB - Analysis of gene expression data sets reveals that the variation in expression is concentrated to significantly fewer 'characteristic modes' or 'eigengenes' than the number of both recorded assays and measured genes. Previous works have stressed the importance of these characteristic modes, but neglected the equally important weak modes. Herein a generic system property - interampatteness - is defined that explains the previous feature, and assigns equal weight to the characteristic and weak modes. An interampatte network is characterised by strong INTERactions enabling simultaneous AMPlification and ATTEnuation of different signals. It is postulated that biochemical networks are interampatte, based on published experimental data and theoretical considerations. Existence of multiple time-scales and feedback loops is shown to increase the degree of interampatteness. Interampatteness has strong implications for the dynamics and reverse engineering of the network. One consequence is highly correlated changes in gene expression in response to external perturbations, even in the absence of common transcription factors, implying that interampatte gene regulatory networks erroneously may be assumed to have co-expressed/co-regulated genes. Data compression or reduction of the system dimensionality using clustering, singular value decomposition, principal component analysis or some other data mining technique results in a loss of information that will obstruct reconstruction of the underlying network. [Includes supplementary material]. PMID- 21028928 TI - Quantifying evolvability in small biological networks. AB - The authors introduce a quantitative measure of the capacity of a small biological network to evolve. The measure is applied to a stochastic description of the experimental setup of Guet et al. (Science 2002, 296, pp. 1466), treating chemical inducers as functional inputs to biochemical networks and the expression of a reporter gene as the functional output. The authors take an information theoretic approach, allowing the system to set parameters that optimise signal processing ability, thus enumerating each network's highest-fidelity functions. All networks studied are highly evolvable by the measure, meaning that change in function has little dependence on change in parameters. Moreover, each network's functions are connected by paths in the parameter space along which information is not significantly lowered, meaning a network may continuously change its functionality without completely losing it along the way. This property further underscores the evolvability of the networks. PMID- 21028930 TI - Scalable learning of large networks. AB - Cellular networks inferred from condition-specific microarray data can capture the functional rewiring of cells in response to different environmental conditions. Unfortunately, many algorithms for inferring cellular networks do not scale to whole-genome data with thousands of variables. We propose a novel approach for scalable learning of large networks: cluster and infer networks (CIN). CIN learns network structures in two steps: (a) partition variables into smaller clusters, and (b) learn networks per cluster. We optionally revisit the cluster assignment of variables with poor neighbourhoods. Results on networks with known topologies suggest that CIN has substantial speed benefits, without substantial performance loss. We applied our approach to microarray compendia of glucose-starved yeast cells. The inferred networks had significantly higher number of subgraphs representing meaningful biological dependencies than random graphs. Analysis of subgraphs identified biological processes that agreed well with existing information about yeast populations under glucose starvation, and also implicated novel pathways that were previously not known to be associated with these populations. [Includes supplementary material]. PMID- 21028931 TI - Identification of gene interactions in fungal-plant symbiosis through discrete dynamical system modelling. AB - Fungal-plant root associations involve nutrient exchanges, between the partners and the soil, particularly phosphate, that benefit both organisms. Discrete dynamical system (DDS) models are reconstructed to capture gene regulation in the arbuscular mycorrhizae Glomus versiforme-Medicago trunculata root symbiosis. Previously published time-course gene expression data derived from various days post-inoculation were clustered to identify genes co-regulated in mycorrhizal roots. Uncolonised roots grown with high phosphate provide a key nutritional control condition. First-order linear DDS models were created using a data-driven method to fit to the observed gene expression data. The result of the modelling constitutes active gene interactions in the regulatory network of the plant root at 8, 15, 22, 31 and 36 days post-inoculation. These genes are involved in basic metabolism, development, oxidative stress and defense pathways, and show consistent dynamic behaviours in the model. The functions of previously unannotated genes were further elucidated from the developed system maps. PMID- 21028932 TI - Mesoscopic statistical properties of multistep enzyme-mediated reactions. AB - Enzyme-mediated reactions may proceed through multiple intermediate conformational states before creating a final product molecule, and one often wishes to identify such intermediate structures from observations of the product creation. In this study, the authors address this problem by solving the chemical master equations for various enzymatic reactions. A perturbation theory analogous to that used in quantum mechanics allows the determination of the first (n) and the second (sigma2) cumulants of the distribution of created product molecules as a function of the substrate concentration and the kinetic rates of the intermediate processes. The mean product flux V=d(n)/dt (or 'dose-response' curve) and the Fano factor F= sigma2/(n) are both realistically measurable quantities, and whereas the mean flux can often appear the same for different reaction types, the Fano factor can be quite different. This suggests both qualitative and quantitative ways to discriminate between different reaction schemes, and the authors explore this possibility in the context of four sample multistep enzymatic reactions. Measuring both the mean flux and the Fano factor can not only discriminate between reaction types, but can also provide some detailed information about the internal, unobserved kinetic rates, and this can be done without measuring single-molecule transition events. PMID- 21028933 TI - Mixed-method exploratory study of general practitioner and nurse perceptions of a new community based nurse-led heart failure service. AB - INTRODUCTION: The treatment of patients with chronic heart failure (CHF) remains sub-optimal. Specialist CHF nurses are proven to improve care and reduce admission but developing such services, especially in remote areas, can be difficult. This study aimed: first, to assess the perceived acceptability and effectiveness of a new community based nurse-led heart failure service by general practitioners (GPs) in an area with a dispersed population; second, to assess the knowledge and learning needs of GPs; and third, to assess perceptions of the use of national guidelines and telehealth on heart failure management. METHODS: The study was conducted in the Scottish Highlands, a large geographical area in the north of the UK which includes both rural and urban populations. The area has a total population of 240 000, approximately 60% of whom are within 1 hour travel time of the largest urban centre. A postal survey of all GPs (n = 260) and structured email survey of all CHF specialist nurses (n = 3) was performed. All responses were entered into a Microsoft Excel spreadsheet, summarised and subjected to thematic analysis. Differences between GPs in 'rural', 'urban' or both 'urban & rural' was investigated using an F-test for continuous variables and a three-sample test for equality of proportions for nominal data. RESULTS: Questionnaires were returned from 83 GPs (32%) and all three CHF specialist nurses. In this sample there were only a few differences between GPs from 'rural', 'urban' and 'urban & rural'. There also appeared to be little difference in responses between those who had the experience of the CHF nurse service and those who had not. Overall, 32 GPs (39%) wished better, local access to echocardiography, while 63 (76%) wished access to testing for brain natriuretic peptide (BNP). Only 27 GPs (33%) referred all patients with CHF to hospital. A number of GPs stated that this was dependant on individual circumstances and the patient's ability to travel. The GPs were confident to initiate standard heart failure drugs although only 54 (65%) were confident in the initiation of beta blockers. Most GPs (69%) had had experience of the CHF specialist nurse service and the responses were mixed. The GPs who had experienced the service appeared less confident that it would lead to reduced admission of patients to hospital (51% vs 77%, p = 0.046). Three main themes emerged from the nurse responses: service planning, communication and attitudinal changes after service embedment. CONCLUSIONS: This study demonstrates that a community based heart failure nurse service was not universally valued. Differences between urban and rural localities (communication) suggest that models of care derived from evidence based practice in urban areas may not be directly transferable to remote areas. Clearly, good communication among staff groups at all stages of implementation is important; however, despite best efforts and clinical trial evidence, specialist nurse services will not be welcomed by all doctors. Service providers and commissioners should be cognisant of the different roles of urban and rural GPs when designing such services. Among GPs there was a high degree of confidence with initiation and titration of drugs for heart failure with the exception of beta-blockers so clearly this is an area of ongoing educational need and support. Education and support should focus on ensuring that all doctors who care for patients with CHF have the skills and confidence to use medical therapies and specialist services as appropriate. PMID- 21028934 TI - Pandemic flu knowledge among dormitory housed university students: a need for informal social support and social networking strategies. AB - INTRODUCTION: The declaration of a Phase 6 pandemic of influenza A (H1N1) by the World Health Organization in June 2009, triggered the activation of preparedness responses worldwide. During 2009 spring and fall, many US universities actuated their emergency pandemic preparedness plans. This article describes a research study that used a modified community based participatory research (CBPR) approach between August and November 2009 at New Mexico State University's main Las Cruces campus to determine influenza (pandemic influenza A (H1N1) 2009 and seasonal influenza knowledge, attitudes, and health communication (informal support networks and social networking) strategies specifically related to influenza among dormitory housed (on-campus living) undergraduate students. The goal was to produce data for use in the university's pandemic illness/disaster preparedness and response plans. METHODS: Following activation of the university's campus-wide efforts to educate students about pandemic flu, university community partners were asked for input regarding information for flu preparedness for the university's undergraduate students. Student participants were recruited for the present study from those housed in four campus dormitories. A purposive convenience sample was used to collect survey data from 175 students during the peak week of reported flu cases on campus. Each participant was given an anonymous, face-to-face, self-administered survey and 167 surveys were able to be analyzed. A chi2 goodness of fit test was used to determine whether observed proportions of categorical variables differed from hypothesized proportions. RESULTS: Four categorical data were analyzed by topics: (1) demographics; (2) flu awareness; (3) flu immunization knowledge and practices; and (4) communication and health information practices. The average age was 19.6 years (SD = 1.8), with no significant differences by sex (86 males and 76 females, 5 undisclosed) or race/ethnicity (57 White, 43 Hispanic, 44 Other). All questions were tested with chi2 against sex, race, and dormitory; however, only three questions revealed statistically significant differences by any of these demographic categories. CONCLUSIONS: Sex, race, age, and dormitory were demonstrated to have little impact on H1N1 health practices and knowledge. Three-quarters of students surveyed demonstrated awareness of the pandemic 2009 H1N1 flu. Despite public health and university health education campaigns, approximately 25% were not aware of the virus. Most students stated that they knew someone who had flu during the year, even if they had not. Students did not perceive (60%) dormitory living to be a greater health risk, even though the proximal distance among students diminishes by sharing bathrooms and sleeping quarters. Three main factors affected the students' knowledge, attitudes and behaviors: faculty attitudes and influenza knowledge; low levels of flu like illnesses at the university; and the utilization of health education strategies inconsistent with the mechanisms students use to gain health information (informal support networks and electronic social networking). Failure to utilize these student information mechanisms may result in less than optimal health education effectiveness. Health educators should ensure that identifiable intermediaries (eg faculty) understand and assist in health education efforts. However, the incidence of H1N1 at this university was relatively low, which may have affected the research results. PMID- 21028935 TI - Evaluation of a combined therapeutic regimen of 8-OH-DPAT and environmental enrichment after experimental traumatic brain injury. AB - When provided individually, both the serotonin (5-HT(1A))-receptor agonist 8 hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and environmental enrichment (EE) enhance behavioral outcome and reduce histopathology after experimental traumatic brain injury (TBI). The aim of this study was to determine whether combining these therapies would yield greater benefit than either used alone. Anesthetized adult male rats received a cortical impact or sham injury and then were randomly assigned to enriched or standard (STD) housing, where either 8-OH DPAT (0.1 mg/kg) or vehicle (1.0 mL/kg) was administered intraperitoneally once daily for 3 weeks. Motor and cognitive assessments were conducted on post-injury days 1-5 and 14-19, respectively. CA1/CA3 neurons and choline acetyltransferase positive (ChAT(+)) medial septal cells were quantified at 3 weeks. 8-OH-DPAT and EE attenuated CA3 and ChAT(+) cell loss. Both therapies also enhanced motor recovery, acquisition of spatial learning, and memory retention, as verified by reduced times to traverse the beam and to locate an escape platform in the water maze, and a greater percentage of time spent searching in the target quadrant during a probe trial in the TBI + STD + 8-OH-DPAT, TBI + EE + 8-OH-DPAT, and TBI + EE + vehicle groups versus the TBI + STD + vehicle group (p <= 0.0016). No statistical distinctions were revealed between the TBI + EE + 8-OH-DPAT and TBI + EE + vehicle groups in functional outcome or CA1/CA3 cell survival, but there were significantly more ChAT(+) cells in the former (p = 0.003). These data suggest that a combined therapeutic regimen of 8-OH-DPAT and EE reduces TBI induced ChAT(+) cell loss, but does not enhance hippocampal cell survival or neurobehavioral performance beyond that of either treatment alone. The findings underscore the complexity of combinational therapies and of elucidating potential targets for TBI. PMID- 21028936 TI - Interaction of nanoparticles and cell-penetrating peptides with skin for transdermal drug delivery. AB - Topical or transdermal drug delivery is challenging because the skin acts as a natural and protective barrier. Therefore, several methods have been examined to increase the permeation of therapeutic molecules into and through the skin. One approach is to use the nanoparticulate delivery system. Starting with liposomes and other vesicular systems, several other types of nanosized drug carriers have been developed such as solid lipid nanoparticles, nanostructured lipid carriers, polymer-based nanoparticles and magnetic nanoparticles for dermatological applications. This review article discusses how different particulate systems can interact and penetrate into the skin barrier. In this review, the effectiveness of nanoparticles, as well as possible mode of actions of nanoparticles, is presented. In addition to nanoparticles, cell-penetrating peptide (CPP)-mediated drug delivery into the skin and the possible mechanism of CPP-derived delivery into the skin is discussed. Lastly, the effectiveness and possible mechanism of CPP-modified nanocarriers into the skin are addressed. PMID- 21028938 TI - Dynamic and cellular interactions of nanoparticles in vascular-targeted drug delivery. AB - Vascular-targeted drug delivery systems could provide more efficient and effective pharmaceutical interventions for treating a variety of diseases including cardiovascular, pulmonary, inflammatory, and malignant disorders. However, several factors must be taken into account when designing these systems. The diverse blood hemodynamics and rheology, and the natural clearance process that tend to decrease the circulation time of foreign particles all lessen the probability of successful carrier interaction with the vascular wall. An effective vascular-targeted drug delivery system must be able to navigate through the bloodstream while avoiding immune clearance, attach to the vascular wall, and release its therapeutic cargo at the intended location. This review will summarize and analyze current literature reporting on (1) nanocarrier fabrication methods and materials that allow for optimum therapeutic encapsulation, protection, and release; (2) localization and binding dynamics of nanocarriers as influenced by hemodynamics and blood rheology in medium-to-large vessels; (3) blood cells' responses to various types of nanocarrier compositions and its effects on particle circulation time; and (4) properties that affect nanocarrier internalization at the target site. PMID- 21028939 TI - Global women's health in 2010: facing the challenges. AB - Women's health is closely linked to a nation's level of development, with the leading causes of death in women in resource-poor nations attributable to preventable causes. Unlike many health problems in rich nations, the cure relies not only on the discovery of new medications or technology but also getting basic services to the people who need them most and addressing underlying injustice. In order to do this, political will and financial resources must be dedicated to developing and evaluating a scaleable approach to strengthen health systems, support community-based programs, and promote widespread campaigns to address gender inequality, including promoting girls' education. The Millennium Development Goals (MDGs) have highlighted the importance of addressing maternal health and promoting gender equality for the overall development strategy of a nation. We must capitalize on the momentum created by this and other international campaigns and continue to advocate for comprehensive strategies to improve global women's health. PMID- 21028937 TI - Receptor-targeted nanocarriers for therapeutic delivery to cancer. AB - Efficient and site-specific delivery of therapeutic drugs is a critical challenge in clinical treatment of cancer. Nano-sized carriers such as liposomes, micelles, and polymeric nanoparticles have been investigated for improving bioavailability and pharmacokinetic properties of therapeutics via various mechanisms, for example, the enhanced permeability and retention (EPR) effect. Further improvement can potentially be achieved by conjugation of targeting ligands onto nanocarriers to achieve selective delivery to the tumour cell or the tumour vasculature. Indeed, receptor-targeted nanocarrier delivery has been shown to improve therapeutic responses both in vitro and in vivo. A variety of ligands have been investigated including folate, transferrin, antibodies, peptides and aptamers. Multiple functionalities can be incorporated into the design of nanoparticles, e.g., to enable imaging and triggered intracellular drug release. In this review, we mainly focus on recent advances on the development of targeted nanocarriers and will introduce novel concepts such as multi-targeting and multi functional nanoparticles. PMID- 21028940 TI - The evaluation of novel natural products as inhibitors of human glutathione transferase P1-1. AB - Glutathione transferase P1-1 is over expressed in some cancer cells and contributes to detoxification of anticancer drugs, leading to drug-resistant tumors. The inhibition of human recombinant GSTP1-1 by natural plant products was investigated using 10 compounds isolated from plants indigenous to Southern and Central Africa. Monochlorobimane and 1-chloro-2,4-dinitrobenzene were used to determine GST activity. Each test compound was screened at 33 and 100 uM. Isofuranonapthoquinone (1) (from Bulbine frutescens) showed 68% inhibition at 33 uM, and sesquiterpene lactone (2) (from Dicoma anomala) showed 75% inhibition at 33 MUM. The IC(50) value of 1 was 6.8 MUM. The mode of inhibition was mixed, partial (G site) and noncompetitive (H site) with K(i) values of 8.8 and 0.21 uM, respectively. Sesquiterpene 2 did not inhibit the CDNB reaction. Therefore, isofuranonapthoquinone 1 needs further investigations in vivo because of its potent inhibition of GSTP1-1 in vitro. PMID- 21028941 TI - Pancreatic lipase inhibition activity of trilactone terpenes of Ginkgo biloba. AB - The prevalence of obesity is increasing at an alarming rate, but, unfortunately, only a few drugs are currently available on the market. In the present study, the methanolic extract of Ginkgo biloba L. (Ginkgoaceae) was investigated as an inhibitor of pancreatic lipase (PL) in an attempt to explain its hypolipidaemic activity. In vitro assay of G. biloba leaves extract revealed a substantial PL inhibition activity (IC(50) = 16.5 ug/mL). Further investigation was performed by employing theoretical docking simulations and experimental testing to uncover the active constituents responsible for G. biloba anti-lipase activity. Virtually, terpene trilactones, including ginkgolides and bilobalide, were found to fit within the binding pocket of PL via several attractive interactions with key amino acids. Experimentally, ginkgolides A, B, and bilobalide were found to inhibit PL significantly (IC(50) = 22.9, 90.0, and 60.1 ug/mL, respectively). Our findings demonstrated that the hypolipidaemic effects of G. biloba extract can be attributed to the inhibition of PL by, at least in part, terpene trilactones. In conclusion, this work can be considered a new step towards the discovery of new natural safe hypolipidaemic PL inhibitors. PMID- 21028942 TI - Evaluation of 3-(4'-(4"-fluorophenyl)-6'-phenylpyrimidin-2'-yl)-2 phenylthiazolidin-4-one for in vivo modulation of biomarkers of chemoprevention in the 7,12-dimethylbenz[a]anthracene-induced hamster buccal pouch carcinogenesis. AB - A new bis heterocycle comprising both bioactive 2-aminopyrimidine and thiazolidin 4-one nuclei namely 3-(4'-(4"-fluorophenyl)-6'-phenylpyrimidin-2'-yl)-2 phenylthiazolidin-4-one 3 was synthesized, characterized with the help of melting point, elemental analysis, FT-IR, MS, one-dimensional NMR ((1)H, (13)C) spectra and we evaluated the chemopreventive potential of 3-(4'-(4"-fluorophenyl)-6' phenylpyrimidin-2'-yl)-2-phenylthiazolidin-4-one based on in vivo inhibitory effects on 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch carcinogenesis. Administration of 3 effectively suppressed oral carcinogenesis initiated with DMBA as revealed by the reduced incidence of neoplasms. Lipid peroxidation, glutathione (GSH) content, and the activities of glutathione peroxidase (GPx), glutathione S-transferase (GST) were used to biomonitor the chemopreventive potential of 3. Lipid peroxidation was found to be significantly decreased, whereas GSH, GPx, GST, and GGT were elevated in the oral mucosa of tumor-bearing animals. Our data suggest that 3 may exert its chemopreventive effects in the oral mucosa by modulation of lipid peroxidation and enhancing the levels of GSH, GPx, and GST. PMID- 21028943 TI - Synthesis and antimicrobial studies of novel 2,4-diaryl-3-azabicyclo[3.3.1]nonan 9-one 4'-phenylthiosemicarbazones. AB - New series of 2,4-diaryl-3-azabicyclo[3.3.1]nonan-9-one 4' phenylthiosemicarbazones (compounds 9-16) was obtained from the corresponding 2,4 diaryl-3-azabicyclo[3.3.1]nonan-9-ones. The synthesized compounds have been characterized by their elemental, analytical, and spectral studies. Besides, these reported compounds were screened for their antibacterial and antifungal activities against a spectrum of microbial organisms. These studies proved that against bacteria, compounds 10 and 11 against Bacillus subtilis, compound 13 against Salmonella typhi, show maximum inhibition potency at low concentration (6.25 MUg/mL), whereas against fungal, compounds 11, 13, and 16 against Candida albicans and compounds 12 and 13 against Cryptococcus neoformans, showed beneficial antifungal activity at minimum concentration (6.25 MUg/mL). PMID- 21028944 TI - Abstracts of the XVI International Congress of ISPOG (International Society of Psychosomatic Obstetrics and Gynecology). Venezia, Italy. October 28-30, 2010. PMID- 21028945 TI - In vitro interactions among echinocandins against Aspergillus fumigatus: lack of concordance among methods. AB - Drug combinations are increasingly being explored as a means of improving outcomes in cases of invasive aspergillosis. However, the optimal methods for assessing in vitro drug combinations are unclear. We investigated whether echinocandin drug combinations have potentially useful interactions against Aspergillus fumigatus. We explored the in vitro interactions of three echinocandins (caspofungin [CSP], anidulafingin [ANF], and micafungin [MCF]) by three methods, i.e., (i) checkerboard assay, (ii) disk diffusion assay, and (iii) E-test/agar dilution. The checkerboard experiments revealed different interactions between echinocandin pairs depending on the drug combination tested. Specifically, the combination of CSF and either ANF or MCF yielded a fractional inhibitory concentration (FIC) index range of 0.15-2.0. Whereas the combination of MCF and ANF yielded an FIC index range of 0.19-0.31, consistent with synergistic interaction. In contrast, all echinocandin pairs appeared indifferent by the disk diffusion method. Moreover, the combination of MCF and ANF appeared antagonistic when the two drugs were tested using the E-test/agar dilution method with both the FKS1 wild-type and echinocandin-resistant fks1 mutant strains. Our results highlight methodological problems inherent in in vitro antifungal combination testing. We did not find compelling evidence of inter-echinocandin synergy that could serve as a basis for further in vivo experimentation. PMID- 21028946 TI - Primary cutaneous cryptococcosis caused by Cryptococcus gattii in an immunocompetent host. AB - This paper presents the case of a 75-year-old Brazilian man who developed inflammatory skin lesions with nodules and ulcerations on the right forearm after an injury caused by handling barbed-wire and Eucalyptus spp. logs. Histopathological assessment of the lesions showed granulomatous processes with yeasts similar to Cryptococcus spp. Tissue fragments yielded yeasts when cultured that were identified as Cryptococcus gattii VGII through biochemical reactions and URA5-RFLP genotype. No evidence of systemic involvement or any underlying immunosuppressive diseases were identified, which supported the diagnosis of primary cutaneous cryptococcosis. After 5 months on therapy with high fluconazole doses, the skin lesions had fully healed. PMID- 21028947 TI - Mitochondria and sulfide: a very old story of poisoning, feeding, and signaling? AB - Sulfide is a molecule with toxicity comparable to that of cyanide. It inhibits mitochondrial cytochrome oxidase at submicromolar concentrations. However, at even lower concentrations, sulfide is a substrate for the mitochondrial electron transport chain in mammals, and is comparable to succinate. This oxidation involves a sulfide quinone reductase. Sulfide is thus oxidized before reaching a toxic concentration, which explains why free sulfide concentrations are very low in mammals, even though sulfide is constantly released as a result of cellular metabolism. It has been suggested that sulfide has signaling properties in mammals like two other gases, NO and CO, which are also cytochrome oxidase inhibitors. The oxidation of sulfide by mitochondria creates further complexity in the description/use of sulfide signaling in mammals. In fact, in the many studies reported in the literature, the sulfide concentrations that have been used were well within the range that affects mitochondrial activity. This review focuses on the relevance of sulfide bioenergetics to sulfide biology and discusses the case of colonocytes, which are routinely exposed to higher sulfide concentrations. Finally, we offer perspectives for future studies on the relationship between the two opposing aspects of this Janus-type molecule, sulfide. PMID- 21028948 TI - In vitro model for IgE mediated food allergy. AB - BACKGROUND: In intestinal food allergy, the non-specificity of gastrointestinal symptoms and the limited access to the reacting organ are the reasons for the limited understanding of the pathophysiology of this disease and the difficulties in establishing an appropriate diagnosis in the individual patient. OBJECTIVE: To develop an in vitro model reproducing pathophysiological mechanisms of IgE mediated food allergy. METHODS: Distal duodenum biopsies of nine patients with food allergy and 10 control subjects were cultured for 3 h with medium alone and with 1 mg/ml of peptic-tryptic digest of wheat gliadin, wheat albumins, and apple proteins. Each biopsy was used for conventional histological examination and for immunohistochemical detection of IgE-positive cells. We have also analyzed the expression of tight junction proteins, occludin, claudin-1, and ZO-1 by immunoconfocal microscopy. Histamine and tryptase release were measured in the culture medium and collected at 0, 30 min, and 3 h of culture using an enzyme and radio immunoassay, respectively. RESULTS: Exposure of small intestinal biopsy specimens of patients with food allergy to food allergens led to a significative increase of IgE-positive cells with a significative increase of histamine and tryptase release and an altered expression of tight junction proteins. No differences were found in intestinal biopsies of controls, cultured with or without food antigens. CONCLUSIONS: Small intestinal organ culture is a functional model of food allergy and could be considered as an in vitro oral food challenge, with evident reduction of costs and risks for the patients. PMID- 21028949 TI - High-resolution melting analysis using unlabeled probe and amplicon scanning simultaneously detects several lactase persistence variants. AB - Lactase persistence and thereby tolerance to lactose is a common trait in people of Northern European descent. It is linked to the LCT -13910C>T variant located in intron 13 of the MCM6 gene 13.9 kb upstream of the lactase (LCT) gene. In people of African and Middle Eastern descent, lactase persistence can be associated with other variants nearby the -13910C>T variant, limiting the use of the -13910C>T-based SNP analysis, e.g. TaqMan assays for the diagnosis of lactose intolerance. Using high-resolution melting analysis, we identified five samples that were heterozygous for the -13915T>G variant among 78 patients genotyped as 13910C/C by a TaqMan assay. All samples originated from patients of probable Middle Eastern descent. In order to detect the -13910 and -13915 variants simultaneously, we developed a new high-resolution melting (HRM) analysis assay based on unlabeled probe genotyping and simultaneous amplicon scanning analysis. By using this assay we were able to distinguish the -13910 and -13915 genotypes clearly. Furthermore, we identified two rare variants, the -13907C>G and 13913T>C. With this method, based on an inexpensive unlabeled probe, it is possible to simultaneously detect the -13910C>T and -13915T>G variants in addition to rarer variants surrounding the -13910 site. This new method may contribute to improve the diagnostic performance of the genetic analysis for lactose intolerance. PMID- 21028950 TI - Biomechanical finite element analysis of small diameter and short dental implant. AB - Abstract Short and mini dental implants have been widely used as treatment alternatives in certain selected clinical situations. However, a profound scientific analysis of the mechanical and biomechanical impact of the reduced length and diameter of these implant geometries has not been published until now. Using finite element analysis, a series of different experimentally designed short and mini implants have been analysed with regard to their load transfer to the alveolar bone and have been compared to respective standard commercial implants. Mini implants have been inserted in an idealised bone bed representing the anterior mandibular jaw region and loaded with a force of 150 N. An immediate loading condition was assumed and analysed using the contact analysis option of the FE package MSC.Marc/Mentat. Short implants were inserted in an idealised posterior bone segment and loaded in osseointegrated state with forces of 300 N. Clearly increased bone loading was observed for the short and mini dental implants compared with standard implants, clearly exceeding the physiological limit of 100 MPa. The determined biomechanical characteristics could explain the slightly increased failure rate of short and mini dental implants. PMID- 21028951 TI - Characterization, biodistribution and targeting evaluation of breviscapine lipid emulsions following intravenous injection in mice. AB - Breviscapine lipid emulsions were prepared by a high speed dispersion homogenization method with optimal formulation and technological method. The proportion of liposomes in breviscapine lipid emulsions, an important character for determining the behavior of drug in vivo belongs to which carriers, was less than 5%. Loading breviscapine into lipid emulsions did increase the breviscapine concentrations in plasma, retarded the clearance, and exhibited the properties of sustained-release concluded by pharmacokinetic parameters: after bolus administration, the elimination phase (t(1/2(beta)) = 99.535) of lipid emulsions was 5.4-times longer than that of Injectio Breviscapine. The AUC(0->infinity) (14.453-times), k(10) (0.047-times), Cl(s) (0.147-times), and MRT(0->infinity) (17.766-times) values also confirmed this trend. The amount of drug in every tissue increased at different levels after intravenous administration of breviscapine lipid emulsions compared with Injectio Breviscapine. The relative exposure value of breviscapine lipid emulsions for plasma and lungs were 29.59 and 5.81, respectively, indicating that the exposure of breviscapine to plasma and lungs was significantly increased by entrapment in lipid emulsions. Other targeting evaluation indexes also proved the superiority of lipid emulsions carrier to deliver drug to the targeting region of vascular and lung diseases therapy. PMID- 21028952 TI - Triamcinolone-loaded glutaraldehyde cross-linked chitosan microspheres: prolonged release approach for the treatment of rheumatoid arthritis. AB - The use of glucocorticoids in the treatment of rheumatoid arthritis has been widely employed, but, owing to their systemic side-effects and also their susceptibility to the first pass metabolism, their use is being discouraged. To circumvent this, triamcinolone (TA) were encapsulated in chitosan microspheres with glutaraldehyde as the cross-linking agent to achieve a prolonged drug release. The percentage of drug loading, encapsulation efficiency, and surface morphology by Scanning electron microscopy (SEM), Phase transition by Differential scanning colorimetry (DSC), as well as Fourier transform infrared spectroscopy (FTIR) studies was carried out to characterize the chitosan microspheres. In-vitro and in-vivo release studies revealed that microspheres were able to control the release of TA with a uniform release pattern up to a period of 36 days and thereafter an extended release up to 63 days. The clinical parameters were investigated for changes in paw volume, hematological parameters like Erythrocyte sedimentation rate (ESR), Paced cell volume (PCV), Total leucocyte count (TLC), Hb, and Differential cell count (DCC) in Fruend's complete adjuvant induced arthritic rats. Histopathological findings as well as radiology (X-ray) further confirmed the effectiveness of TA encapsulated microspheres in mitigating the rat arthritic model. PMID- 21028953 TI - Clinical experience with the combined contraceptive vaginal ring in Switzerland, including a subgroup analysis of previous hormonal contraceptive use. AB - OBJECTIVE: To collect data on cycle and cycle-related symptoms during a second clinical experience programme with the contraceptive vaginal ring (NuvaRing(r)) in Switzerland. METHODS: Women requiring contraception were recruited by gynaecologists. Questionnaires were used to collect data on cycle and related symptoms, weight, satisfaction and adverse events at baseline and follow-up (typically four cycles). RESULTS: Of the 1053 women included, 36.9% were starters, 22.4% starters anew, and 40.6% switchers. At follow-up, improvement in cycle regularity was significantly better for starters compared with switchers (18.5% versus 11%; p < 0.001). Starters showed the greatest improvement in bleeding duration and severity. Improvement in the severity of premenstrual symptoms (PMS) and dysmenorrhoea was significantly (p < 0.001) greater in starters compared with switchers (18.5% vs. 9.1% and 26.5% vs. 9.8%, respectively). Menstrual headache improved in all subgroups. Women were satisfied with changes in weight (92%), cycle control (93.6%) and PMS (86%). Adverse events were reported for 17.5% of women and were most frequently ring-related (such as feeling the ring in situ, vaginal discomfort, ring expulsion). CONCLUSIONS: The data support previous findings that the vaginal ring improves cycle-related symptoms (moderate or severe PMS, dysmenorrhoea, and menstrual headache). Not only starters experienced improvements in symptoms; switchers also benefited. PMID- 21028954 TI - Efficacy of whole-cell killed bacterial vaccines in preventing pneumonia and death during the 1918 influenza pandemic. AB - BACKGROUND: Most deaths in the 1918 influenza pandemic were caused by secondary bacterial pneumonia. METHODS: We performed a systematic review and reanalysis of studies of bacterial vaccine efficacy (VE) in preventing pneumonia and mortality among patients with influenza during the 1918 pandemic. RESULTS: A meta-analysis of 6 civilian studies of mixed killed bacterial vaccines containing pneumococci identified significant heterogeneity among studies and estimated VE at 34% (95% confidence interval [CI], 19%-47%) in preventing pneumonia and 42% (95% CI, 18% 59%) in reducing case fatality rates among patients with influenza, using random effects models. Using fixed-effect models, the pooled VE from 3 military studies was 59% (95% CI, 43%-70%) for pneumonia and 70% (95% CI, 50%-82%) for case fatality. Military studies showed less heterogeneity and may provide more accurate results than civilian studies, given the potential biases in the included studies. Findings of 1 military study using hemolytic streptococci also suggested that there was significant protection. CONCLUSIONS: Despite significant methodological problems, the systematic biases in these studies do not exclude the possibilities that whole-cell inactivated pneumococcal vaccines may confer cross-protection to multiple pneumococcal serotypes and that bacterial vaccines may play a role in preventing influenza-associated pneumonia. PMID- 21028955 TI - Direct and indirect effectiveness of influenza vaccination delivered to children at school preceding an epidemic caused by 3 new influenza virus variants. AB - BACKGROUND: Influenza is an uncontrolled epidemic disease that is vaccine preventable. New recommendations for universal immunization present a challenge to the implementation of vaccine delivery. This field trial examines the effectiveness of school-based clinics for vaccine delivery before an epidemic caused by 3 new influenza virus variants not contained in the vaccine. METHODS: Live attenuated influenza vaccine (LAIV) was offered to eligible children in elementary schools of eastern Bell County, Texas. Age-specific rates of medically attended acute respiratory illness for health plan members at the intervention site were compared with those for members at comparison sites during the epidemic, defined by viral surveillance at all sites. RESULTS: Almost 48% of children in elementary schools were vaccinated. Significant herd protection attributed to LAIV was detected for all age groups except 12-17-year-old students, who were not offered free vaccine. Approximately 2500 medical encounters were prevented at the intervention site. Inactivated vaccine provided marginal protection against the epidemic viruses. CONCLUSIONS: LAIV delivered to elementary-school children before an epidemic caused by 3 new variant influenza viruses generated significant cross-protection for the recipients and indirect (herd) protection for the community. PMID- 21028956 TI - A paradigm for the control of influenza. PMID- 21028957 TI - Higher seroprevalence of Trypanosoma cruzi infection in dogs than in humans in an urban area of Campeche, Mexico. AB - The reservoir capacity of dogs for Trypanosoma cruzi infection was analyzed in the city of Campeche, an urban town located in the Yucatan peninsula in Mexico. The city is inhabited by ~96,000 dogs and ~168,000 humans; Triatoma dimidiata is the only recognized vector. In the present study, we sampled 262 dogs (148 stray dogs and 114 pet dogs) and 2800 young people (ranging in age between 15 and 20 years old) and tested for T. cruzi antibodies by enzyme-linked immunosorbent assay, Indirect Immunofluorescence, and Western blotting serological assays. Seroprevalence in stray dogs was twice higher than in pet dogs (9.5% vs. 5.3%) with general seroprevalence of 7.6%. In humans, the observed seroprevalence was 76 times lower than in dogs (0.1% vs. 7.6%, respectively). Western blotting analysis showed that dogs' antibodies recognized different T. cruzi antigenic patterns than those for humans. In conclusion, T. cruzi infection in Campeche, Mexico, represents a low potential risk to inhabitants but deserves vigilance. PMID- 21028958 TI - West Nile virus finally debuts in British Columbia 10 years after its introduction to North America. AB - Since its first detection in New York (1999), West Nile virus (WNv) has spread across the United States and Canada with the first activity reported in Canada in 2001. By 2004, WNv had been detected almost in every province of Canada and the contiguous regions of the United States with the exception of British Columbia (BC), this despite being detected in Alberta in 2003 and Washington as early as 2002. In August 2009, two human cases were serologically found to have WNv infection. They reported mosquito bites and had only traveled in the South and Central Okanagan areas of BC before their presentation. On the basis of clinical, laboratory, and epidemiological data, these two human cases have been confirmed as the first locally acquired WNv cases in BC. Various factors may have contributed to the 10-year delay in the spread of WNv to BC, including regional weather conditions and unique topography. PMID- 21028959 TI - Differentiation of medically important Euro-Asian tick species Ixodes ricinus, Ixodes persulcatus, Ixodes hexagonus, and Dermacentor reticulatus by polymerase chain reaction. AB - Understanding epidemiology of the tick-borne pathogens requires the accurate identification of the vector ticks. Morphological analysis of ticks is difficult and often leads to misidentification. Molecular techniques offer an alternative approach of tick identification. To date, no practical and reliable molecular assays for discrimination of Euro-Asian ticks are available. Our aim was to develop such an assay for discrimination between four Euro-Asian tick species of high medical importance such as Ixodes ricinus, Ixodes persulcatus, Ixodes hexagonus, and Dermacentor reticulatus. As a basis, we have chosen conventional species-specific polymerase chain reaction (PCR), a technique providing a good combination of simplicity and reliability. The DNA information available on ticks was searched for orthologous loci containing stretches of sequence dissimilarity sufficient for designing species-specific primers. ITS2 locus (second internal transcribed region of the rRNA gene cluster) was found to be the most favorable for primer design. Finally, for each of the three Ixodes species a PCR was developed amplifying only for the targeted species. One PCR amplified the entire ITS2 locus of the four species and allowed discrimination of D. reticulatus from the Ixodes species on the basis of the size difference of the respective PCR products. This PCR system was successfully tested for discrimination of the ticks at different maturation stages (larva, nymph, and adult) in engorged and unfed conditions, and therefore it may be useful for large-scale epidemiological studies. Differentiation between the closely related I. ricinus and I. persulcatus, the two species most often occurring in the tick-borne diseases in Eurasia, is of special importance. PMID- 21028960 TI - Detection, isolation, and genetic characterization of Rift Valley fever virus from Anopheles (Anopheles) coustani, Anopheles (Anopheles) squamosus, and Culex (Culex) antennatus of the Haute Matsiatra region, Madagascar. AB - Following veterinary alerts of Rift Valley fever (RVF) in the districts of Fianarantsoa I and II in November 2008 and in the district of Ambalavao in April 2009, entomological and virological investigations were carried out to identify the mosquito species that could act as RVF virus (RVFV) vectors in the region. A total of 12,785 adult mosquitoes belonging to 5 genera and 21 species were collected. After identification, mosquitoes were pooled by species, sex, and female status (fed or unfed) and then stored at -80 degrees C. Of 319 pools of unfed monospecific female mosquito tested by real-time RT-polymerase chain reaction, RVFV was detected in 1 pool of Anopheles coustani, 5 pools of An. squamosus, and 2 pools of Culex antennatus mosquitoes. The virus was isolated in mosquito cell lines from two of the five Real Time-RT-polymerase chain reaction (real time-RT-PCR) positive pools of An. squamosus mosquitoes. From the eight RVFV strains detected, partial S, M, and L genome segments sequences were obtained. The phylogenetic analysis of these sequences showed that the strains circulating in mosquitoes were genetically close to those that circulated in livestock and humans during RVF outbreaks in 2008 and 2009. This study, therefore, provides strong evidence that An. squamosus, An. coustani, and Cx. antennatus could play a role as vectors of the RVFV during the disease outbreaks in 2008-2009. Bioecological, genetic, and RVF transmission studies on these three mosquito species are needed to address this question and thus improve prevention and control of future RVF outbreaks in Madagascar, where these species are present. PMID- 21028961 TI - Crimean-Congo hemorrhagic fever in European part of Turkey: genetic analysis of the virus strains from ticks and a seroepidemiological study in humans. AB - A survey of ticks from domestic ruminants, together with a serosurvey in humans was conducted in Thrace (northwestern Turkey) to evaluate the prevalence of Crimean-Congo hemorrhagic fever virus (CCHFV) in ticks and humans. More prevalent ticks were Hyalomma marginatum, Hyalomma aegyptium, Rhipicephalus bursa, and Rhipicephalus (Boophilus) annulatus, with low numbers of Dermacentor marginatus, Rhipicephalus sanguineus group, and Ixodes ricinus. No differences in the tick faunal composition were found among surveyed provinces. CCHFV was detected using specific primers for strains belonging to both Europe 1 and Europe 2 clades in a total of 15 pools of ticks collected in nine localities. The maximum likelihood estimate of infection rate was calculated as 0.72/100 ticks (95% CI = 0.42-1.16). Viral RNA was observed only in H. marginatum, R.(B.) annulatus, and R. bursa with overall maximum likelihood estimate infection rates being 0.93 (95% CI = 0.35 2.05), 0.74 (95% CI = 0.24-1.78), and 1.67 (95% CI = 0.69-3.46), respectively. The surveyed region is the only place where both viral strains are circulating together in nature in Turkey. Results from serosurvey on 193 samples from three localities in the region showed that immunoglobulin M and immunoglobulin G rates are compatible with an epidemiological situation in which the virus has been present for a long time and is not the result of a recent invasive event from the main epidemic center in Anatolia (north-central Turkey). Seropositivity rates cannot be compared against the tick faunal composition, because of the homogeneity in the results about tick surveys. The high rate of seropositivity, and the prevalence of CCHFV in both Europe 1 and 2 clades among the ticks, but few clinical cases suggest that the circulation of both viral strains may confer protection against the CCHFV infection. PMID- 21028962 TI - Prevalence and molecular characterization of tick-borne encephalitis virus in Ixodes ricinus ticks collected in Slovenia. AB - The hard tick Ixodes ricinus is the principal vector of tick-borne encephalitis virus (TBEV) in Slovenia; but until now, there was no information about the prevalence of TBEV infection in Slovenian ticks. We conducted a 2-year survey in 2005 and 2006, during which we were collecting I. ricinus ticks monthly in eight different locations of Slovenia. A total of 4777 I. ricinus ticks were collected: 1515 in year 2005 and 3262 in year 2006. The collected ticks were pooled into groups from which total RNA was extracted. Viral RNA was detected using real-time RT-polymerase chain reaction (PCR). Ticks infected with TBEV were found in six of eight locations. Viral RNA was detected in 8 of the 230 pools of ticks collected in 2005 and in 14 of the 442 pools collected in 2006. Prevalence of TBEV infection in Slovenian ticks was determined as 0.47%: 0.54% in 2005 and 0.43% in 2006. The detected infection rate in ticks significantly correlates with the TBEV incidence rates in selected areas. Using the method of sequencing, we have confirmed that the TBEV in ticks is genetically related to the TBEV in Slovenian patients. PMID- 21028963 TI - Toxoplasmosis in naturally infected rodents in Belgrade, Serbia. AB - To assess the role of synanthropic rodents in the epidemiology of urban toxoplasmosis, Toxoplasma gondii infection was examined in 144 rats (Rattus norvegicus) and 12 mice (Mus musculus) captured using live animal traps in three locations in Belgrade city characterized by poor housing and degraded environment. In rats, specific IgG antibodies were detected by modified agglutination test in 22 (27.5%) of the 80 blood samples available. Toxoplasma brain cysts were microscopically detected in 11 (7.6%), and Toxoplasma DNA by real-time polymerase chain reaction was demonstrated in 15 (10.4%) animals. Of these, both cysts and Toxoplasma DNA were detected in five (3.5%) rats. In mice, cysts were observed in 3 (25%), but Toxoplasma DNA was detected in even 10 (83.3%) animals, including all 3 with morphologically recognized cysts. Being a link in the chain of Toxoplasma infection, the existence of urban rodent reservoirs of infection represents a public health risk. PMID- 21028964 TI - 2'-O-methyl-modified anti-MDR1 fork-siRNA duplexes exhibiting high nuclease resistance and prolonged silencing activity. AB - The thermodynamic asymmetry of siRNA duplexes determines their silencing activity. Favorable asymmetry can be achieved by incorporation of mismatches into the 3' part of the sense strand, providing fork-siRNAs, which exhibit higher silencing activity and higher sensitivity to nucleases. Recently, we found that selective 2'-O-methyl modifications of the nuclease-sensitive sites of siRNA significantly improve its nuclease resistance without substantial loss of silencing activity. Here, we examined the impact of nucleotide mismatches and the number and location of 2'-O-methyl modifications on the silencing activity and nuclease resistance of anti-MDR1 siRNAs. We found that both nonmodified and selectively modified fork-siRNAs with 4 mismatches at the 3' end of the sense strand suppress the expression of target gene at lower effective concentrations than the parent siRNAs with classical duplex design. The selective modification of nuclease-sensitive sites significantly improved the stability of fork-siRNAs in the presence of serum. The selectively modified fork-siRNA duplexes provided inhibitory effect over a period of 12 days posttransfection, whereas the gene silencing activity of the nonmodified analogs expired within 6 days. Thus, selective chemical modifications and structural alteration of siRNA duplexes improve their silencing properties and significantly prolong the duration of their silencing effect. PMID- 21028965 TI - Environmental contamination in the hospital as a possible source for nosocomial infection with methicillin-resistant Staphylococcus aureus. PMID- 21028967 TI - Highlight: The biology of aging: mechanisms and intervention. PMID- 21028966 TI - Improving efficiency in active surveillance for methicillin-resistant Staphylococcus aureus or vancomycin-resistant Enterococcus at hospital admission. AB - OBJECTIVE: Mandatory active surveillance culturing of all patients admitted to Veterans Affairs (VA) hospitals carries substantial economic costs. Clinical prediction rules have been used elsewhere to identify patients at high risk of colonization with methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant enterococci (VRE). We aimed to derive and evaluate the clinical efficacy of prediction rules for MRSA and VRE colonization in a VA hospital. Design and setting. Prospective cohort of adult inpatients admitted to the medical and surgical wards of a 119-bed tertiary care VA hospital. METHODS: Within 48 hours after admission, patients gave consent, completed a 44-item risk factor questionnaire, and provided nasal culture samples for MRSA testing. A subset provided perirectal culture samples for VRE testing. RESULTS: Of 598 patients enrolled from August 30, 2007, through October 30, 2009, 585 provided nares samples and 239 provided perirectal samples. The prevalence of MRSA was 10.4% (61 of 585) (15.0% in patients with and 5.6% in patients without electronic medical record (EMR)-documented antibiotic use during the past year; P < .01). The prevalence of VRE was 6.3% (15 of 239) (11.3% in patients with and 0.9% in patients without EMR-documented antibiotic use; P < .01). The use of EMR documented antibiotic use during the past year as the predictive rule for screening identified 242.8 (84%) of 290.6 subsequent days of exposure to MRSA and 60.0 (98%) of 61.0 subsequent days of exposure to VRE, respectively. EMR documentation of antibiotic use during the past year identified 301 (51%) of 585 patients as high-risk patients for whom additional testing with active surveillance culturing would be appropriate. CONCLUSIONS: EMR documentation of antibiotic use during the year prior to admission identifies most MRSA and nearly all VRE transmission risk with surveillance culture sampling of only 51% of patients. This approach has substantial cost savings compared with the practice of universal active surveillance. PMID- 21028968 TI - Inhibition of interferon-alpha-induced signaling by hyperosmolarity and hydrophobic bile acids. AB - Apart from viral conditions, host factors such as elevated bile acid concentrations are determinants of successful interferon-alpha (IFN-alpha) treatment in patients with chronic hepatitis C or B. The present study demonstrates that hydrophobic bile acids inhibit Jak1- and Tyk2-phosphorylation, which lead to blockade of STAT1-mediated IFN-alpha-signaling in the sodium taurocholate cotransporting peptide (NTCP)-transfected human hepatoma cell line HepG2, resulting in a decreased mRNA and protein expression of IFN-stimulated genes such as myxovirus resistance protein A (MxA) or dsRNA-activated protein kinase (PKR). In addition, hyperosmotic stress leads to an inhibition of IFN alpha-induced Jak1- and Tyk2-phosphorylation, and STAT1/STAT2-phosphorylation and gene expression. This inhibitory effect of hydrophobic bile acids or hyperosmolarity is not due to caspase-mediated cleavage or lysosomal degradation of the cognate receptors or to the generation of oxidative stress, activation of p38- or Erk-mediated MAPK pathways or phosphatase activity. Preincubation with the organic osmolyte betaine blocked the inhibitory effect of bile acids or hyperosmolarity on MxA protein expression, but had no effect on transcript levels or activation of STAT1, suggesting that betaine mediates its effects on MxA expression at a translational or post-translational level. Our findings could provide a rationale for betaine use in cholestatic HBV/HCV patients undergoing interferon therapy. PMID- 21028969 TI - Effect of zinc supplementation on markers of insulin resistance, oxidative stress, and inflammation among prepubescent children with metabolic syndrome. AB - OBJECTIVE: This trial aimed to evaluate the effects of zinc sulfate in comparison with placebo on markers of insulin resistance, oxidative stress, and inflammation in a sample of obese prepubescent children. METHODS: This triple-masked, randomized, placebo-controlled, crossover trial was conducted among 60 obese Iranian children in 2008. Participants were randomly assigned to two groups of equal number; one group received 20 mg of elemental zinc and the other group received placebo on a regular daily basis for 8 weeks. After a 4-week washout period, the groups were crossed over. In addition to anthropometric measures and blood pressure, fasting plasma glucose, lipid profile, insulin, apolipoproteins A 1 (ApoA-I) and B, high-sensitivity C-reactive protein (hs-CRP), leptin, oxidized low-density lipoprotein (ox-LDL), and malondialdehyde were determined at all four stages of the study. RESULTS: Irrespective of the order of receiving zinc and placebo, in both groups, significant decrease was documented for Apo B/ApoA-I ratio, ox-LDL, leptin and malondialdehyde, total and LDL-cholesterol after receiving zinc without significant change after receiving placebo. In groups, hs CRP and markers of insulin resistance decreased significantly after receiving zinc, but increased after receiving placebo. In both groups, the mean body mass index (BMI) Z-score remained high, after receiving zinc, the mean weight, BMI, BMI Z-score decreased significantly, whereas these values increased after receiving placebo. CONCLUSION: These results are particularly important in light of the deleterious consequences of childhood obesity and early changes in markers of inflammatory and oxidative stress. We suggest exploring the direct clinical application of zinc supplementation in childhood obesity in future studies. PMID- 21028971 TI - Introduction to the special issue: neurobiology and building interpersonal systems: groups, couples, and beyond. PMID- 21028972 TI - Integrating interpersonal neurobiology with group psychotherapy. AB - An understanding of the principles of neuroscience that illuminate how interpersonal relationships shape the brain, especially as articulated by interpersonal neurobiology (IPNB) (Siegel, 1999), may help group therapists 1) increase their holding capacity, 2) offer patients a framework that can decrease shame and increase regulation, and 3) identify methods of group interaction that can foster neuroplasticity, support neural integration, and lead to greater well being and more fulfilling relationships. This paper introduces several aspects of neuroscience and discusses how therapist awareness and sharing of this knowledge with group participants at the right empathic moment can be both a psychoeducational support and a promoter of neural integration. While numerous neuroscience topics may be of help, here we will suggest three: early brain development, including the nature of implicit, explicit, and autobiographical memory; group as a source of regulation (with a brief mention of mirror neurons); and four domains of neural integration that are particularly useful in the setting of group therapy. PMID- 21028973 TI - Commentary on "integrating interpersonal neurobiology with group psychotherapy": reflections on mind, brain, and relationships in group psychotherapy. PMID- 21028974 TI - Mirror neurons: their implications for group psychotherapy. AB - Recently discovered mirror neurons in the motor cortex of the brain register the actions and intentions of both the organism and others in the environment. As such, they may play a significant role in social behavior and groups. This paper considers the potential implications of mirror neurons and related neural networks for group therapists, proposing that mirror neurons and mirror systems provide "hard-wired" support for the group therapist's belief in the centrality of relationships in the treatment process and exploring their value in accounting for group-as-a-whole phenomena. Mirror neurons further confirm the holistic, social nature of perception, action, and intention as distinct from a stimulus response behaviorism. The implications of mirror neurons and mirroring processes for the group therapist role, interventions, and training are also discussed. PMID- 21028975 TI - Developing the group mind through functional subgrouping: linking systems centered training (SCT) and interpersonal neurobiology. AB - This article introduces the systems-centered concept of the "group mind" by linking systems-centered thinking and interpersonal neurobiology, building on Siegel's definition of mind as the process of regulating the flow of energy and information. Functional subgrouping, the systems-centered group method for resolving conflicts, discriminates and integrates the flow of energy and information within and between group members, subgroups, and the group-as-a whole, thus potentiating survival, development, and transformation. This article uses the interpersonal neurobiological framework to discuss functional subgrouping as a tool for developing the group mind: considering how functional subgrouping facilitates emotional regulation, creates a secure relational context, and potentiates neural integration. PMID- 21028976 TI - Group psychotherapy and neuro-plasticity: an attachment theory perspective. AB - This article selectively highlights relevant areas of neuroscience research which have direct application for attachment theory and group psychotherapy. Emerging evidence from the neurosciences is revealing that the developing brain of the infant, sculpted by the earliest attachment relationships, continues to be malleable in adulthood and can be profoundly influenced by ongoing relationships throughout one's lifespan. Advances in the neurosciences are also supporting the idea that strong attachment bonds and external interpersonal interactions that arise within the context of these attachments are registered as a person's neurophysiology and neurobiology. Attachment theory in particular provides a common language and conceptual framework from which the contributions from the neurosciences can be made applicable to group psychotherapy. PMID- 21028977 TI - Introducing couples to group therapy: pursuing passion through the neo-cortex. AB - Revolutionary developments in the study of neurobiology and relationships have led to new approaches in the treatment of couples. This paper describes a program of couples groups that utilizes a neurobiological perspective in combining education with group experience. The educational part of the program integrates findings from neurobiology, a biological view of affect dysregulation and attachment theory, and helps partners learn to slow down their physiological intensity before taking risks and exploring attachment to one another. PMID- 21028978 TI - Commentary on the neurobiology of group psychotherapy: group and the social brain: speeding toward a neurobiological understanding of group psychotherapy. PMID- 21028981 TI - A comparison of pupil dilation and induction of corneal endothelial apoptosis by intracameral 1% lidocaine versus 1:100,000 epinephrine in rabbits. AB - PURPOSE: The aim of this study was to evaluate the mydriatic effects of intracameral 1% lidocaine compared with 1:100,000 epinephrine and the effect on endothelial apoptosis in rabbits. METHODS: Forty eyes of 20 New Zealand white rabbits were divided into 2 equal groups. In the first group, 1 eye was injected intracamerally with 1% lidocaine (lidocaine eyes) and the fellow eye with 1:100,000 epinephrine (epinephrine eyes). In the second group, 1 eye was injected with balanced salt solution (BSS eye) and the fellow eye was instilled with 1% tropicamide (mydriatics eye). Specular microscopy, transmission electron microscopy, scanning electron microscopy, and TdT-mediated dUTP nick-end labeling staining were performed 1 day postinjection. RESULTS: Both the full-dilation time and pupil diameters of the lidocaine and epinephrine eyes were not significantly different (P > 0.05). The endothelial cytoplasmic vacuolizations were increased and microprojections were diminished in the epinephrine eyes compared with the mydriatics, BSS, and lidocaine eyes (P < 0.05). Apoptosis was demonstrated in only epinephrine eyes, with an index of 5%. CONCLUSIONS: In rabbits, the intracameral injections of preservative-free 1% lidocaine may be used as an adjunctive method with topical mydriatics in cataract surgery, as like 1:100,000 epinephrine. The intracameral 1% lidocaine may induce less microstructural alterations to the corneal endothelial cells than 1:100,000 epinephrine. PMID- 21028982 TI - Good manufacturing practices production of mesenchymal stem/stromal cells. AB - Because of their multi/pluripotency and immunosuppressive properties mesenchymal stem/stromal cells (MSCs) are important tools for treating immune disorders and for tissue repair. The increasing use of MSCs has led to production processes that need to be in accordance with Good Manufacturing Practice (GMP). In cellular therapy, safety remains one of the main concerns and refers to donor validation, choice of starting material, processes, and the controls used, not only at the batch release level but also during the development of processes. The culture processes should be reproducible, robust, and efficient. Moreover, they should be adapted to closed systems that are easy to use. Implementing controls during the manufacturing of clinical-grade MSCs is essential. The controls should ensure microbiological safety but also avoid potential side effects linked to genomic instability driving transformation and senescence or decrease of cell functions (immunoregulation, differentiation potential). In this rapidly evolving field, a new approach to controls is needed. PMID- 21028983 TI - Lessons from a community-based infection prevention study. PMID- 21028984 TI - Chlorhexidine-impregnated cloths to prevent skin and soft-tissue infection in Marine recruits: a cluster-randomized, double-blind, controlled effectiveness trial. AB - BACKGROUND: Community-associated methicillin-resistant Staphylococcus aureus (CA MRSA) causes skin and soft-tissue infection (SSTI) in military recruits. OBJECTIVE: To evaluate the effectiveness of 2% chlorhexidine gluconate (CHG) impregnated cloths in reducing rates of SSTI and S. aureus colonization among military recruits. DESIGN: A cluster-randomized (by platoon), double-blind, controlled effectiveness trial. SETTING: Marine Officer Candidate School, Quantico, Virginia, 2007. PARTICIPANTS: Military recruits. INTERVENTION: Application of CHG-impregnated or control (Comfort Bath; Sage) cloths applied over entire body thrice weekly. MEASUREMENTS: Recruits were monitored daily for SSTI. Baseline and serial nasal and/or axillary swabs were collected to assess S. aureus colonization. RESULTS: Of 1,562 subjects enrolled, 781 (from 23 platoons) underwent CHG-impregnated cloth application and 781 (from 21 platoons) underwent control cloth application. The rate of compliance (defined as application of 50% or more of wipes) at 2 weeks was similar (CHG group, 63%; control group, 67%) and decreased over the 6-week period. The mean 6-week SSTI rate in the CHG impregnated cloth group was 0.094, compared with 0.071 in the control group (analysis of variance model rate difference, 0.025 +/- 0.016; P = .14). At baseline, 43% of subjects were colonized with methicillin-susceptible S. aureus (MSSA), and 2.1% were colonized with MRSA. The mean incidence of colonization with MSSA was 50% and 61% (P = .026) and with MRSA was 2.6% and 6.0% (P = .034) for the CHG-impregnated and control cloth groups, respectively. CONCLUSIONS: CHG impregnated cloths applied thrice weekly did not reduce rates of SSTI among recruits. S. aureus colonization rates increased in both groups but to a lesser extent in those assigned to the CHG-impregnated cloth intervention. Antecedent S. aureus colonization was not a risk factor for SSTI. Additional studies are needed to identify effective measures for preventing SSTI among military recruits. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier: NCT00475930. PMID- 21028985 TI - Artemisinin resistance in Cambodia: a clinical trial designed to address an emerging problem in Southeast Asia. AB - BACKGROUND: Increasing rates of failure of artemisinin-based combination therapy have highlighted the possibility of emerging artemisinin resistance along the Thai-Cambodian border. We used an integrated in vivo-in vitro approach to assess the presence of artemisinin resistance in western Cambodia. This article provides additional data from a clinical trial that has been published in The New England Journal of Medicine. METHODS: Ninety-four adult patients from Battambang Province, western Cambodia, who presented with uncomplicated falciparum malaria were randomized to receive high-dose artesunate therapy (4 mg/kg/day orally for 7 days) or quinine-tetracycline. Plasma concentrations of dihydroartemisinin, in vitro drug susceptibility, and molecular markers were analyzed. Cases meeting all the following criteria were classified as artemisinin resistant: failure to clear parasites within 7 days of treatment or reemergence of parasites within 28 days of follow-up; adequate plasma concentrations of dihydroartemisinin; prolonged parasite clearance; and increased in vitro drug susceptibility levels for dihydroartemisinin. RESULTS: Two (3.3%) of 60 artesunate-treated patients were classified as artemisinin resistant. Their parasite clearance times were prolonged (133 and 95 h, compared with a median of 52.2 h in patients who were cured). These patients had 50% inhibitory concentrations of dihydroartemisinin that were almost 10 times higher than the reference clone W2. Resistance did not appear to be mediated by the pfmdr1 copy number or selected PfATPase6 polymorphisms previously proposed to confer artemisinin resistance. CONCLUSION: Artemisinin resistance has emerged along the Thai-Cambodian border. The potentially devastating implications of spreading resistance to a drug that currently has no successor call for further studies of this emerging problem. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT00479206. PMID- 21028986 TI - Tuberculosis due to Mycobacterium bovis in patients coinfected with human immunodeficiency virus. AB - We reviewed 86 cases of human immunodeficiency virus and tuberculosis coinfection; 34.9% were caused by Mycobacterium bovis. Patients with M. bovis infection were more likely to have advanced immunosuppression (CD4 T cell counts <=200 cells/MUL). Hispanic ethnicity, male sex, and abdominal disease were strongly associated with M. bovis disease. PMID- 21028988 TI - Prognostic influence and magnetic resonance imaging findings in paroxysmal sympathetic hyperactivity after severe traumatic brain injury. AB - Paroxysmal sympathetic hyperactivity (PSH) is a clinical syndrome affecting a subgroup of survivors of severe brain injury. In this study, the prevalence, magnetic resonance imaging (MRI) presentation, influence on the clinical course in the intensive care unit (ICU), and effect on neurological recovery of PSH were prospectively surveyed in 87 patients with severe traumatic brain injury (TBI). Cranial MRI was performed during the first 30 days after injury. The outcome was assessed according to the Glasgow Outcome Scale (GOS). PSH occurred in 18.4% of patients, with a greater incidence among younger patients and those with lower Glasgow Coma Scale (GCS) scores. Patients with PSH had more deep lesions as shown on cranial MRI, significantly longer ICU stays, and worse outcomes. PSH was shown to be common among patients with severe TBI who also had deep intraparenchymal lesions. The mechanism by which PSH influences patient outcomes has yet to be defined, but we believe that it may be mediated by diencephalic-mesencephalic dysfunction or disconnection. PMID- 21028989 TI - Part II: crystalline fluorapatite-coated hydroxyapatite implant material: a dog study with histologic comparison of osteogenesis seen with FA-coated HA grafting material versus HA controls: potential bacteriostatic effect of fluoridated HA. AB - Success of osteogenesis in bone graft procedures can be enhanced by inhibiting oral bacterial infections through the use of prophylactic bacteriostatic fluoride within the grafting environment. Ideally, the fluoride ion should be chemically sequestered and thus unavailable unless needed at times during the process of early infection. As fluoride within fluorapatite is tightly bound at neutral pH and becomes available only during acidic conditions, fluorapatite is an ideal store for the fluoride ion which becomes released for bacteriostasis only during an acidic environment found with incipient bacterial infection. The purpose of this investigation was to compare the histologic properties of new bone formed surrounding fluorapatite (FA)-coated microcrystalline hydroxyapatite (HA) grafting material with comparable bone formed following the use of control HA material (OsteoGen, Impladent, Ltd, Holliswood, NY). The results of histologic analysis within dog studies here showed no detectable difference in new bone following therapeutic grafting procedures using each of the above 2 mineral coatings. PMID- 21028987 TI - Flavin redox switching of protein functions. AB - Flavin cofactors impart remarkable catalytic diversity to enzymes, enabling them to participate in a broad array of biological processes. The properties of flavins also provide proteins with a versatile redox sensor that can be utilized for converting physiological signals such as cellular metabolism, light, and redox status into a unique functional output. The control of protein functions by the flavin redox state is important for transcriptional regulation, cell signaling pathways, and environmental adaptation. A significant number of proteins that have flavin redox switches are found in the Per-Arnt-Sim (PAS) domain family and include flavoproteins that act as photosensors and respond to changes in cellular redox conditions. Biochemical and structural studies of PAS domain flavoproteins have revealed key insights into how flavin redox changes are propagated to the surface of the protein and translated into a new functional output such as the binding of a target protein in a signaling pathway. Mechanistic details of proteins unrelated to the PAS domain are also emerging and provide novel examples of how the flavin redox state governs protein-membrane interactions in response to appropriate stimuli. Analysis of different flavin switch proteins reveals shared mechanistic themes for the regulation of protein structure and function by flavins. PMID- 21028990 TI - Part III: crystalline fluorapatite-coated hydroxyapatite; potential use as a bacteriostatic agent for both pre-implant cases and retreatment of infected implant sites: a report of 4 cases. AB - Four cases of peri-implant bone loss associated with undiagnosed necrotic pulps of adjacent teeth are reported. In two cases, bone was obliterated along sinus tracts (fistulas) that coursed between the implant and adjacent tooth. Endodontic treatment was completed on the adjacent teeth concurrent with periapical surgery to seal the tooth apex. The sinus tract (fistula) was excised, and the implant plus tooth surfaces were treated with a combination of concentrated citric acid and 4.3% sodium fluoride solutions. The third case involved peri-implant surgery with endodontic treatment on the adjacent tooth. A fourth case represented an infected socket augmentation which was surgically treated, augmented with microcrystalline fluorapatite in the range of a 300 um to 400 um cluster, and allowed to heal for 4 months followed by a trephine bone biopsy and subsequent analysis for bone growth around the fluoridated nonceramic microcrystalline hydroxyapatite (HA). An augmentation procedure employing fluoridated of resorbable HA was then completed. Histologic analysis showed healthy bone regeneration suggesting that therapeutic fluoride treatment and resultant fluorapatite were helpful in inhibiting reinfection following surgical treatment. All 4 infected implant sites were successfully managed and retained using the aforementioned treatment schemes, and there was no evidence of posttreatment infection in any of the 4 cases. It is proposed that fluoride treatment, through the use of 4.3% sodium fluoride and/or fluoridated hydroxyapatite (fluorapatite), shows promise as an adjunctive treatment component in inhibiting peri-implant infection and reinfection when managing ailing or failing implants. PMID- 21028991 TI - Statewide experience with Clostridium difficile colitis in academic and non academic medical centers. AB - BACKGROUND: Clostridium difficile colitis is a nosocomial infection that can present as minor, readily treated symptoms or as fulminant colitis leading to death. Risk factors for C. difficile colitis have been defined, and certain populations of hospitalized patients appear to be particularly susceptible. However, most information on C. difficile colitis is from large tertiary-care medical centers. Whether the community hospital experience is similar to that of large referral centers is unknown. METHODS: We abstracted all cases of C. difficile colitis (ICD-9-CM 008.45) for 2003-2005 from a state database and divided the hospitals into academic and nonacademic centers. Cases were stratified according to whether the colitis was listed as the primary presenting diagnosis or a secondary diagnosis. Demographic information, associated diagnoses, length of stay, and deaths were analyzed. RESULTS: The incidence of C. difficile colitis increased from 2003 to 2005, and the majority of cases occurred at nonacademic centers. Patients in nonacademic centers more frequently had C. difficile colitis as the primary diagnosis, had a shorter length of stay, were older, and were more frequently women. The mortality rate was higher for secondary (8.5%) than for primary (2.6%; p < 0.05) C. difficile colitis, but there was no difference between academic and nonacademic centers. CONCLUSIONS: The incidence of C. difficile colitis is increasing in this statewide database. Compared with academic medical centers, nonacademic centers deal with a higher rate of primary C. difficile colitis that is associated with a lower mortality rate and shorter stay than secondary colitis. PMID- 21028993 TI - The combined effect of hypertension and smoking on arterial stiffness. AB - Arterial stiffness plays a critical role in the function of the cardiovascular system as it represents the coupling of the left ventricle and arterial tree. Increased arterial stiffness is associated with a number of cardiovascular complications. Increased stiffness occurs with age and with the development of chronic conditions (e.g., hypertension) and the presence of vascular risk factors (e.g., smoking). Measuring arterial stiffness is increasingly gaining popularity as a method of assessing cardiovascular health and treatment efficacy. The purpose of this review was to assess the combined effect of hypertension and smoking on arterial stiffness. A systematic review of the literature revealed four relevant studies; hypertension and smoking were found to be independent detrimental factors for raising arterial stiffness, and combined they raise arterial stiffness more than either solitary factor. However, a need was identified for future studies to determine the extent to which smoking cessation therapy combined with the appropriate anti-hypertensive medication can lead to stabilization or even reversal of arterial stiffness. PMID- 21028992 TI - Akt increases sox2 expression in adult hippocampal neural progenitor cells, but increased sox2 does not promote proliferation. AB - Multiple extracellular factors have been shown to modulate adult hippocampal neural progenitor cell (NPC) proliferation and self-renewal, and we have previously shown that Akt is an important mediator of the effects of these extracellular factors on NPC proliferation and differentiation. However, very little work has investigated how and whether Akt is involved in maintaining the multipotency of these cells. Here we demonstrate that Akt promotes expression of Sox2, a core transcription factor important for the self-renewal of NPCs. Retroviral-mediated overexpression of wild-type Akt increased Sox2 protein expression, particularly under conditions that promote cell differentiation, whereas Akt inhibition decreased Sox2. Similarly, quantitative reverse transcription (RT)-PCR in differentiating cultures indicated that Akt rescued Sox2 mRNA to levels present under conditions that promote cell proliferation. Additionally, pharmacological inhibition of Akt did not affect Sox2 protein levels in cells constitutively expressing Sox2 from a retroviral vector, indicating that Akt does not affect Sox2 protein stability. Further, in contrast to Akt overexpression, Sox2 overexpression does not increase NPC viable cell number or proliferation yet does inhibit differentiation. Collectively, these results indicate that Akt promotes cell proliferation and maintenance of a multipotent state via two downstream paths. PMID- 21028994 TI - Religious and spiritual beliefs in stroke rehabilitation. AB - Faith could dampen Post-Stroke Depression (PSD), which may negatively influence recovery. The present pilot study is an initial examination of the role of religion and spirituality on the functional recovery after a recent stroke. Data were analyzed from 112 consecutive stroke inpatients, who underwent a 2-month standard rehabilitation program. All participants received the Royal Free Interview (RFI), a semi-structured interview for religious and spiritual beliefs, and were assessed on their mood with the Hospital Anxiety and Depression Scale (HADS). Functional status was measured by means of the Functional Independence Measure (FIM). The relationship between religious beliefs, mood improvements, and functional recovery was explored by means of a multiple linear regression. No association between faith and recovery of functional independence could be verified, neither religiousness as a "coping strategy" was associated with functional recovery in this study. An explorative study of a larger size, which also takes into consideration the cultural background and religious beliefs of all patients, is warranted in the longterm. PMID- 21028995 TI - Differences between hypertensive and atherosclerotic lesions in retinal arteries assessed by Scheie's classification in hypertensive patients following stroke. AB - Scheie's classification regarding hypertensive and atherosclerotic lesions in retinal arteries is generally used to assess the severity of hypertensive retinopathy and the risks of cardiovascular events in hypertensive patients. However, the differences between these two types of retinal artery lesions have not been fully examined. Both arterial stiffness and aortic root diameter are increased in hypertensive patients. The aim of this study was to elucidate differences in the two types of lesions by comparing their relationships to arterial stiffness and aortic root diameter in hypertensive patients following stroke. Fifty-two hypertensive patients following stroke were divided into five stages according to Scheie's classification of hypertensive (H stage 0-4) and atherosclerotic (S stage 0-4) lesions by ophthalmologists. Arterial stiffness was measured as brachial-ankle pulse wave velocity (baPWV) using an automatic waveform analyzer. Aortic root diameter was measured using M-mode echocardiography. The H and S stages in retinal arteries correlated with each other (rho = 0.443, p < 0.001). However, the S stage correlated with baPWV (rho = 0.385, p = 0.005) and the aortic root diameter (rho = 0.285, p = 0.043), while the H stage did not correlate with these parameters. Multiple stepwise regression analysis demonstrated that the aortic root diameter was independently associated with S stage (beta = 0.373, p = 0.006), even though baPWV was independently associated with neither S stage nor H stage. In conclusion, hypertensive lesions (H stage) in retinal arteries are associated with atherosclerotic lesions (S stage) in retinal arteries. However, S stage may reflect arterial stiffening and aortic root dilatation better than H stage in hypertensive patients following stroke. This difference between H and S stages of Scheie's classification should be kept in mind when considering the association between retinal microcirculation and large vessel arteriosclerosis. PMID- 21028996 TI - Pitavastatin further decreases serum high-sensitive C-reactive protein levels in hypertensive patients with hypercholesterolemia treated with angiotensin II, type 1 receptor antagonists. AB - Lipid-lowering therapy with a statin not only powerfully lowers cholesterol but also exerts anti-inflammatory effects by decreasing serum C-reactive protein (CRP). Since an angiotensin II, type-1 receptor antagonist (ARB) also decreases CRP levels, the add-on effect of statins on CRP may be worth exploring. We determined the effect of pitavastatin on serum levels of highly sensitive CRP (hs CRP) in 30 patients with hypercholesterolemia undergoing treatment with anti hypertensive medication including ARBs. Pitavastatin, 2 mg daily, was given. The control group consisted of hypertensive patients without hyperlipidemia. The low density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and hs-CRP were measured at baseline, 1, 3, 6, and 12 months after treatment. For the atherosclerotic index, LDL-C/HDL-C ratios at 12 months were calculated. The LDL-C level was markedly reduced at 1 month and thereafter. The baseline level of hs-CRP in the hyperlipidemia group was significantly higher than that in the control group (1.647 +/- 0.210 mg/L vs. 0.666 +/- 0.097 mg/L p < 0.0001). After 3 months, the percentage of reduction of hs-CRP was significantly higher than that in the control group. The absolute values of hs-CRP were significantly decreased to a level similar to the control group, and the hs-CRP in both groups was remained at the same level for 12 months. Although the LDL C/HDL-C ratios of the pitavastatin group was significantly reduced from 3.3 to 1.8, those of the control group were not changed. In conclusion, pitavastatin was found to have powerful anti-inflammatory, add-on effects over the similar effects of ARB as assessed by hs-CRP. PMID- 21028997 TI - Plasma plasminogen activator inhibitor 1 (PAI-1) and P-selectin levels in urgent hypertension: effect of single dose captopril and nifedipine on fibrinolytic activity. AB - In this study, we primarily aimed to identify the acute effects of hypertension on fibrinolytic function in previously untreated urgent hypertensive patients and to evaluate the influence of two commonly used, short-acting, anti-hypertensive agents, captopril and nifedipine, in these patients. Patient groups were selected homogeneously, i.e., only previously untreated patients amidst an urgent hypertensive episode and having no co-morbid disease were included-and randomly assigned to receive either captopril or nifedipine for immediate management. These two treatment groups were matched for age, gender, and mean arterial blood pressure. Study results demonstrated that lowering blood pressure with either agent improved fibrinolytic function; however, in those patients given captopril, this beneficial effect was more prominent, providing evidence supporting the preferential use of short-acting, angiotensin-converting enzyme (ACE) inhibitors in this setting. PMID- 21028998 TI - Salt and nitric oxide synthase inhibition-induced hypertension: kidney dysfunction and brain anti-oxidant capacity. AB - The specific aim of this study was to examine the effects of salt-loading on kidney function and brain antioxidant capacity. Wistar rats were divided into four groups: Control rats were given normal drinking water and no drug treatment for 2 weeks. LNNA group: rats were given normal drinking water and the nitric oxide (NO) inhibitor NG-nitro-L-arginine (L-NNA), 3 mg/kg/day. LNNA + Salt group: rats were given drinking water containing salt 2% and 3 mg/kg L-NNA. Salt group: rats were given drinking water containing salt 2% and no drug treatment. Basal blood pressure and the levels of serum BUN, creatinine, uric acid, cortisol, electrolyte, serum antioxidant capacity, and oxidative stress were measured. NO, superoxide dismutase (SOD), and catalase (CAT) levels were measured in the hypothalamus, brainstem, and cerebellum. Salt overload increased the blood pressure of the LNNA + Salt group. Salt-loading enhanced BUN, creatinine, sodium retention. High salt produced an increase in uric acid levels and a decrease in cortisol levels in serum. Additionally, the oxidative stress index in serum increased in the LNNA + Salt group. Salt-loading enhanced brain NO levels, but not SOD and CAT activity. L-NNA increased brain SOD activity, but not CAT and NO levels. In conclusion, salt-loading causes hypertension, kidney dysfunction, and enhances oxidative stress in salt-sensitive rats. PMID- 21028999 TI - The relationship between osteopontin and adiponectin in patients with essential hypertension. AB - The renin angiotensin aldosterone system (RAAS) induces inflammation and accelerates atherosclerosis, contributes to both pro- and anti-inflammatory cytokines. Osteopontin (OPN) is known as a pro-inflammatory cytokine and adiponectin is known as an anti-inflammatory cytokine. C-reactive protein (CRP) not only reflects an inflammatory state but also leads to inflammation. Previous studies clarified that OPN and adiponectin were regulated by RAAS. In this study, we hypothesized that plasma OPN level relates to serum adiponectin level in patients with essential hypertension (EHT). Sixty-two patients (32 females) with EHT were enrolled in this study. They were evaluated for conventional risk factors for atherosclerosis, further plasma aldosterone, plasma OPN, serum adiponectin, and CRP levels were assayed. There were significant gender differences in creatinine, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-denisty lipoprotein(LDL) cholesterol, log transformed (ln) adiponectin and ln CRP. Osteopontin was correlated positively with aldosterone and ln CRP (r = 0.277, p = 0.029, r = 0.278, p = 0.029, respectively), negatively with adiponectin (r = -0.346, p = 0.006). Ln adiponectin was correlated positively with HDL cholesterol (r = 0.373, p = 0.003) and negatively with gender (male as 1), creatinine, triglyceride, aldosterone, and ln CRP (r = -0.55, p < 0.001, r = -0.279, p = 0.028, r = -0.406, p = 0.001, r = -0.307, p < 0.015, r = 0.289, p = 0.023, respectively). Stepwise regression analysis showed that adiponectin was an independent predictor of OPN beta= -0.0339, p = 0.004). Our results suggest that OPN and adiponectin are related to each other underlying the mechanisms of RAAS and inflammation. PMID- 21029000 TI - Genetic control of the corticosterone level at rest and under emotional stress in ISIAH rats with inherited stress-induced arterial hypertension. AB - The genetic background of the regulatory systems of the hypothalamic-pituitary adrenal (HPA) axis in hypertension remains unclear. The inherited stress-induced arterial hypertension (ISIAH) and Wistar Albino Glaxo (WAG) normotensive rats were bred and their F(2) progeny were used in a quantitative trait loci (QTL) analysis to identify genomic regions for plasma basal and stress-induced corticosterone levels, and for absolute and relative adrenal gland weights. The significant loci were found for stress-induced corticosterone on chromosome 9 and for adrenal weight on chromosome 6. The results may help to identify the genes controlling the trait phenotypes in the ISIAH rats characterized by the enhanced responsiveness to stressful stimulation. PMID- 21029001 TI - Azelnidipine and amlodipine: a comparison of their effects and safety in a randomized double-blinded clinical trial in Chinese essential hypertensive patients. AB - The purpose of this study is to compare the effects and safety of azelnidipine and amlodipine in Chinese essential hypertensive patients. Patients were randomized to receive administration of azelnidipine 8-16 mg/day or amlodipine 2.5-5 mg/day for 8 weeks. The blood pressure and pulse rate were evaluated in an outpatient clinic and by ambulatory blood pressure monitoring. There were 220 patients enrolled to the study. The blood pressure in both groups was decreased significantly (P < 0.001). Compared with amlodipine, the patients received azelnidipine had better response in systolic blood pressure (SBP) and diastolic blood pressure (DBP) (P < 0.01). No significant changes of pulse rate were observed in either group. For the ambulatory blood pressure monitoring, both drugs had stable anti-hypertensive effects over 24 h. The trough/peak ratios of DBP for the azelnidipine and amlodipine groups were, respectively, 46% and 40%. Adverse events occurred at 7.3% and 10.0%, respectively in the azelnidipine and amlodipine groups (P = 0.485). Headache and dizziness were observed at an incidence of more than 1% in both groups. Once-daily administration of azelnidipine effectively controlled blood pressure and had a stable action over 24 h. Azelnidipine had good safety and compliance similar to amlodipine. PMID- 21029002 TI - The relationship of gamma-glutamyltransferase to aortic elastic properties in young patients with prehypertension. AB - Some cross-sectional studies have demonstrated a positive association between serum gamma-glutamyltransferase (GGT) levels and blood pressure. Accordingly, we aimed to analyze serum GGT levels in patients with prehypertension and examine the relationship with aortic elasticity parameters. The study population consisted of 25 newly diagnosed prehypertensive individuals and 25 healthy control subjects. Aortic strain, distensibility index, and stiffness index beta were calculated from aortic diameters measured by echocardiography and blood pressures simultaneously measured by sphygmomanometry. Prehypertensive patients were detected to have significantly lower aortic distensibility and strain indexes compared to control subjects aortic distensibility. However, aortic stiffness index beta of the prehypertensive group was significantly higher compared to that of the control group (3.73 +/- 1.41 vs. 2.97 +/- 0.82, p = 0.02). The mean GGT levels were found to be higher in patients with prehypertension compared to those of controls (47.9 +/- 15.9 U/L vs. 36.1 +/- 9.4 U/L, p = 0.003). When multiple linear regression analysis was done to clarify the contributions of GGT to aortic elasticity adjusting for age, body mass index, uric acid, serum glucose, heart rate, low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)-cholesterol, and triglyceride, we observed that only serum GGT levels were significantly associated with aortic elasticity parameters (for aortic strain beta = -0.247, p < 0.001; for aortic distensibility beta = -0.108, p < 0.001; for stiffness index beta = 0.063, p < 0.001). Whatever the mechanism is, young patients with prehypertension have higher serum GGT levels compared to healthy control subjects. More importantly, increased GGT levels are independently associated with impaired aortic elasticity in patients with prehypertension. PMID- 21029003 TI - Evaluation of arterial blood pressure and renal sodium handling in a model of female rats in persistent estrus. AB - The aim of this study was to evaluate the arterial blood pressure and renal function of female rats in persistent estrus. Twenty-five female Wistar-Hannover rats were randomly divided into two groups: Group I (control, n = 15) and experimental (persistent estrus, n = 10). A tail-cuff system was used to measure blood pressure at 12 weeks of life. Parameters to evaluate renal function were taken into consideration. A significant increase in arterial pressure and a significant decrease in fractional sodium excretion were found in the androgenized animals compared to controls. There was no difference between the two groups with respect to glomerular filtration rate or in fractional potassium excretion. An increase in blood pressure and a reduction in fractional sodium excretion occur in female rats in persistent estrus. PMID- 21029004 TI - Effect of early diabetes on the response to norepinephrine and dopamine in pithed Wistar Kyoto and spontaneously hypertensive rats. AB - Diabetes has been related to changes in vascular responses, mainly an increase in the vasoconstrictor responses and a decrease in the vasodilator responses. The literature has now begun to study the effects of diabetes in the early stages of development; the first studies on these stages indicate that diabetes produces different changes compared to the advanced stages. For that reason, the aim of this work was to evaluate the responses to norepinephrine and dopamine on normotensive and hypertensive rats with 4 weeks of diabetes evolution. The results showed that 4 weeks of diabetes produces a decrease of the vasopressor response to both agents (norepinephrine and dopamine). These results suggest that in the early stages, there are changes that help to decrease the pressor responses and these changes could disappear in the advanced stages. PMID- 21029005 TI - Ertapenem-resistant Enterobacteriaceae: risk factors for acquisition and outcomes. AB - BACKGROUND AND OBJECTIVE: Carbapenem resistance among Enterobacteriaceae is of concern because of increasing prevalence and limited therapeutic options. Limited research has been focused on understanding ertapenem resistance as a more sensitive marker for resistance to other carbapenems. We sought to determine risk factors for acquisition of ertapenem-resistant, meropenem-susceptible, or intermediate Enterobacteriaceae and to assess associated patient outcomes. DESIGN: Retrospective case-control study among adult hospitalized inpatients. SETTING: A 902-bed quaternary care urban hospital. RESULTS: Sixty-two cases of ertapenem-resistant Enterobacteriaceae were identified from March 14, 2006, through October 31, 2007, and 62 unmatched control patients were randomly selected from other inpatients with cultures positive for ertapenem-susceptible Enterobacteriaceae. Thirty-seven (60%) of case patient isolates were Enterobacter cloacae, 20 (32%) were Klebsiella pneumoniae, and 5 (8%) were other species of Enterobacteriaceae. Risk factors for ertapenem-resistant Enterobacteriaceae infection included intensive care unit stay (odds ratio [OR], 4.6 [95% confidence interval {CI}, 2.0-10.3]), vancomycin-resistant Enterococcus colonization (OR, 7.1 [95% CI, 2.4-21.4]), prior central venous catheter use (OR, 10.0 [95% CI, 3.0 33.1]), prior receipt of mechanical ventilation (OR, 5.8 [95% CI, 2.1-16.2]), exposure to any antibiotic during the 30 days prior to a positive culture result (OR, 18.5 [95% CI, 4.9-69.9]), use of a beta-lactam during the 30 days prior to a positive culture result (OR, 6.9 [95% CI, 3.0-16.0], and use of a carbapenem during the 30 days prior to a positive culture result (OR, 18.2 [95% CI, 2.6 130.0]). For the 62 case patients, 30-day outcomes from the time of positive culture result were 24 discharges (39%), 10 deaths (16%), and 28 continued hospitalizations (44%). The final end point of the hospitalization was discharge for 44 patients (71%) and death for 18 patients (29%). CONCLUSIONS: Ertapenem resistant Enterobacteriaceae are important nosocomial pathogens. Multiple mechanisms of resistance may be in operation. Additional study of ertapenem resistance is needed. PMID- 21029006 TI - Investigation of increased rates of isolation of Bacillus species. AB - BACKGROUND: In 2007-2008, several US hospitals reported summertime increases in the number of clinical blood cultures positive for Bacillus species, which are common environmental bacteria. OBJECTIVE: To investigate increased rates of isolation of Bacillus species from blood cultures, identify risk factors, and recommend control strategies. DESIGN: Survey and case-control study. SETTING: Multiple hospitals, including a cancer center. METHODS: We surveyed 24 facilities that reported increases. We also conducted a field investigation at a hospital with a high rate, reviewing charts, collecting clinical and environmental isolates, and observing infection control procedures. A case-control study compared inpatient case patients who had any blood culture positive for Bacillus with unmatched control patients who had a blood culture with no growth during June-August 2008. RESULTS: Among surveyed facilities, mean monthly rates rose from 25 to a peak of 75 Bacillus-positive blood cultures per 10,000 blood cultures performed during the period June-August. At the hospital where the case control investigation was conducted, for most case patients (75%), the Bacillus positive blood cultures represented contamination or device colonization rather than infection. We enrolled 48 case patients and 48 control patients; in multivariate analysis, only central venous access device use was significantly associated with case status (odds ratio, 14.0; [Formula: see text]). Laboratory testing identified at least 12 different Bacillus species (non-anthracis) among the isolates. Observation of infection control procedures revealed variability in central line care and blood sample collection techniques. CONCLUSIONS: Periodic increases in the environmental load of Bacillus species may occur in hospitals. Our investigation indicated that at one facility, these increases likely represented a pseudo-outbreak of Bacillus species colonizing central venous lines or their accessories, such as needleless connector devices. Vigilant attention should be paid to infection control practices when collecting blood samples for culture, to minimize the risk of contamination by environmental microorganisms. PMID- 21029007 TI - Transmission of influenza A pandemic (H1N1) 2009 virus in a long-term care facility in Ontario, Canada. PMID- 21029009 TI - Sodium tungstate and vanadyl sulfate effects on blood pressure and vascular prostanoids production in fructose-overloaded rats. AB - This study analyzes the effects of sodium tungstate and vanadyl sulphate in the fructose-overloaded rat, a model of metabolic syndrome. Fructose (9 weeks) increased blood pressure, triglycerydemia, glycemia, and reduced release of vasodilator prostaglandins (prostacyclin and prostaglandin E2 ) in the mesenteric vascular bed. Sodium tungstate prevented those alterations; meanwhile vanadyl sulfate only prevented the increase in glycemia. In conclusion, the present experiments showed that sodium tungstate is more effective than vanadyl sulfate for the treatment of experimental metabolic syndrome in rats. PMID- 21029010 TI - Endothelial nitric oxide synthase immunreactivity and the ultrastructure of endothelial cells of umbilical artery in normal and preeclamptic pregnancies. AB - Our objective was to investigate the endothelial nitric oxide synthase (eNOS) immuno-reactivity and the ultrastructure of endothelial cells of a human umbilical artery in both normal and preeclamptic pregnancies. The umbilical cords from normal and preeclamptic pregnancies were collected immediately after vaginal and abdominal deliveries. Umbilical arteries were isolated and fixed in 10% neutral formaline solution, embedded in paraffin, and then stained with hematoxylin and eosin (H&E) for the histologic investigation, and eNOS activation were examined in samples by streptavidine-biotine immunohistochemical methods. The arterial sections were also fixed in phosphate-buffered 2.5% glutaraldehyde solution (pH 7.2) for 3 h and post-fixed with 1% osmium tetroxide at 4 degrees C for 2 h for the investigation of the ultrastructural examination. In the umbilical artery of preeclamptic pregnancies, endothelial cells were oval, triangular, or polygonal, and were disorganized. Some endothelial cells were separated by enlarged intercellular spaces. A dilated endoplasmic reticulum, swollen mitochondria, and vanished mitochondrial cristae were observed. The nuclei of some endothelial cells displayed deep invaginations and irregular outlines. Most endothelial cells had a high number of cytoplasmic vacuoles. In preeclampsia, eNOS immunoreactivity increased considerably in endothelial cells when compared to normal pregnancies. We believe that preeclampsia plays an important role in the pathogenesis of endothelial cell dysfunction and activation in the umbilical artery. However, the disturbance mechanism of endothelial cells is not known, and further studies are necessary to clarify the exact mechanism. PMID- 21029011 TI - The paradox of dopamine and angiotensin II-mediated Na(+), K(+)-ATPase regulation in renal proximal tubules. AB - Accumulated studies reported that the natruretic dopamine (DA) and the anti natruretic angiotensin II (Ang II) represent an important mechanism to regulate renal Na(+) and water excretion through intracellular secondary messengers to inhibit or activate renal proximal tubule (PT) Na(+), K(+)-ATPase (NKA). The antagonistic actions were mediated by the phosphorylation of different position of NKA alpha1-subunit and different Pals-associated tight junction protein (PATJ) PDZ domains, the different protein kinase C (PKC) isoforms (PKC-beta, PKC-zeta), the common adenylyl cyclase (AC) pathway, and the crosstalk and balance between DA and Ang II to NKA regulation. Besides, Ang II-mediated NKA modulation has bi phasic effects. PMID- 21029008 TI - Impact of International Nosocomial Infection Control Consortium (INICC) strategy on central line-associated bloodstream infection rates in the intensive care units of 15 developing countries. AB - BACKGROUND: The International Nosocomial Infection Control Consortium (INICC) was established in 15 developing countries to reduce infection rates in resource limited hospitals by focusing on education and feedback of outcome surveillance (infection rates) and process surveillance (adherence to infection control measures). We report a time-sequence analysis of the effectiveness of this approach in reducing rates of central line-associated bloodstream infection (CLABSI) and associated deaths in 86 intensive care units with a minimum of 6 month INICC membership. METHODS: Pooled CLABSI rates during the first 3 months (baseline) were compared with rates at 6-month intervals during the first 24 months in 53,719 patients (190,905 central line-days). Process surveillance results at baseline were compared with intervention period data. RESULTS: During the first 6 months, CLABSI incidence decreased by 33% (from 14.5 to 9.7 CLABSIs per 1,000 central line-days). Over the first 24 months there was a cumulative reduction from baseline of 54% (from 16.0 to 7.4 CLABSIs per 1,000 central line days; relative risk, 0.46 [95% confidence interval, 0.33-0.63]; P < .001). The number of deaths in patients with CLABSI decreased by 58%. During the intervention period, hand hygiene adherence improved from 50% to 60% (P < .001); the percentage of intensive care units that used maximal sterile barriers at insertion increased from 45% to 85% (P < .001), that adopted chlorhexidine for antisepsis increased from 7% to 27% (P < .001), and that sought to remove unneeded catheters increased from 37% to 83% (P < .001); and the duration of central line placement decreased from 4.1 to 3.5 days (P < .001). CONCLUSIONS: Education, performance feedback, and outcome and process surveillance of CLABSI rates significantly improved infection control adherence, reducing the CLABSI incidence by 54% and the number of CLABSI-associated deaths by 58% in INICC hospitals during the first 2 years. PMID- 21029012 TI - Relation between grade II hypertensive retinopathy and coronary artery disease in treated essential hypertensives. AB - It is known that in advanced hypertensive retinopathy, which changes advanced hypertensive retinopathy (Grade III or IV), there is a strong relation between retinal microvascular lesions and cardiac and macrovascular markers of target organ damage (TOD). The prevalence of grade II hypertensive retinopathy and its relationship to cardiovascular risk factors remain controversial. The subjects, a total of 437 hypertensive patients, were divided into three groups according to modified Keith, Wagener, and Barker (KWB) classification by two ophthalmologists: Grade 0 with normal retinal change (N = 169, 38.7%), Grade I with arteriolar narrowing (N = 215, 49.1%), Grade II with arteriovenous crossings (N = 49, 11.2%). The prevalence of Grade I and Grade II hypertensive retinopathy was significantly higher than that of advanced hypertensive retinopathy. The grade of hypertensive retinopathy was related to age, duration of hypertension, coronary artery disease (CAD), and left ventricular hypertrophy (LVH). The prevalence of LVH and CAD in Grade II was significantly higher than in Grade I and Grade 0. The hypertensive retinopathy Grade II was significantly correlated with LVH (odds ratio (OR) 2.3, 95% confidence interval (CI) 1.21-4.44, p < 0.05) and CAD (OR 4.2, 95% CI 1.97-8.95, p-<-0.001). Grade I and Grade II hypertensive retinopathy are frequently observed in hypertensive patients compared to Grade III and IV patients. We concluded that Grade II hypertensive retinopathy is closely related to CAD and should therefore not be ignored. PMID- 21029013 TI - The relationship between microvascular endothelial function and carotid-radial pulse wave velocity in patients with mild hypertension. AB - Carotid-radial pulse wave velocity (CRPWV) can be measured rapidly using applanation tonometry and significantly higher values have been reported among patients with risk factors for vascular disease. Forearm blood flow responses to intrabrachial infusion of acetylcholine independently predict cardiovascular morbidity among hypertensive patients. We aimed to examine the relationship between CRPWV, a potentially informative, noninvasive measure and this more established parameter of arterial health. One hundred and fifteen mildly hypertensive individuals (67% men, mean (+/- SD) age 54 +/- 8 years, mean (+/- SD) blood pressure (BP) 143 +/- 16/83 +/- 12 mmHg) were recruited from a weekly medical outpatient clinic. Each volunteer had CRPWV measured using sequential tonometry before forearm blood flow responses to intra-arterial, endothelium dependent (acetylcholine) and independent (sodium nitroprusside) vasodilators were assessed. There was a significant negative correlation between CRPWV and maximum forearm blood flow response to acetylcholine (r = -0.225, p = 0.016). This association remained significant in a multiple regression analysis (beta = 0.213, p = 0.034). Mean arterial pressure and weight were additional independent predictors of CRPWV in this model. There was no such relationship between CRPWV and response to sodium nitroprusside (r = 0.088, p = 0.349). In patients with mild hypertension, a poor forearm blood flow response to acetylcholine independently predicted faster CRPWV, thus linking an established measure of microvascular endothelial function with a noninvasive index of conduit vessel stiffness. PMID- 21029014 TI - Are metabolic risk factors and target organ damage more frequent in masked hypertension than in white coat hypertension? AB - Patients with masked hypertension (MH) tend to have a higher risk than those with white-coat hypertension (WCH). Therefore, we evaluated the characteristics of MH and WCH in Korean patients receiving medical treatment for hypertension. We enrolled 1019 outpatients (56 +/- 10 y, 488 males) with diagnosed hypertension who had not changed oral anti-hypertensive medication for 6 months. Clinic blood pressure (CBP) was checked by a nurse and doctor twice per visit. Home BP (HBP) was checked every morning and evening for 1 week. In the MH patients, mean CBP was 130/80 mmHg, whereas HBP was 137/86 mmHg. In the WCH patients, mean CBP was 149/86 mmHg by physician and 143/85 mmHg by nurse and mean HBP was 124/75 mmHg. Age and gender did not differ between the groups. Waist and hip circumferences and the level of fasting glucose were higher in patients with MH than in patients with WCH (p = 0.008, 0.016, 0.009, respectively). Metabolic risk factors were more frequent in patients with WCH, MH, and uncontrolled hypertension than in patients with controlled hypertension. The incidence of metabolic risk factors, however, did not differ between patients with WCH and MH. Heart damage was more frequent in MH than in WCH (p = 0.03). The incidence of metabolic risk factors did not differ between patients with WCH and those with MH. Target organ damage was more closely related to MH than to WCH. Home BP measurement was a useful tool for discriminating WCH and MH in patients with hypertension. PMID- 21029015 TI - The effects of blood pressure lowering on P-wave dispersion in patients with hypertensive crisis in emergency setting. AB - Hypertensive emergency refers to a severe hypertension (HT) that is associated with new or progressive end-organ damage. In these clinical situations, blood pressure (BP) should be reduced immediately to prevent or minimize organ dysfunction. The present study evaluated the diagnostic value of two electrocardiographic indices in detecting patients, who are at risk for paroxysmal atrial fibrillation (PAF), in the setting hypertensive crisis. The study population consisted of 30 consecutive patients aged >=40 years, who were admitted to the emergency room with hypertensive crisis. Electrocardiographic (ECG) recordings of the patients were performed before and after the treatment. The minimum (Pmin) and maximum (Pmax) P wave duration on ECG, and P-wave dispersion (P(d)), which was defined as the difference between Pmin and Pmax, were measured. The mean P(d) was 118.0 +/- 32.1 and 94.0 +/- 44.3 before and after the treatment, respectively. The decrease observed in the mean P(d) was statistically significant (p = 0.005). The mean Pmax was 214.7 +/- 37.1 before the treatment, while it was 194.0 +/- 47.3 after the treatment, and the difference was significant (p = 0.021). The mean Pmin was 96.7 +/- 26.3 and 100.0 +/- 41.0 before and after the treatment, respectively; however, the difference was not significant (p = 0.624). Pmax and P(d) display significant changes with acute treatment of HT. There is a need for larger prospective studies to clearly elucidate the diagnostic value of ECG indices, Pmax and P(d) as indicators of future PAF. PMID- 21029016 TI - A fish out of water: gill and skin remodeling promotes osmo- and ionoregulation in the mangrove killifish Kryptolebias marmoratus. AB - The euryhaline, amphibious mangrove killifish Kryptolebias marmoratus is known to survive weeks out of water in moist environments. We tested the hypothesis that the skin is a site of osmo- and ionoregulation in K. marmoratus. We predicted that under terrestrial conditions, gill and skin remodeling would result in an enhanced role for skin and a diminished role for the gills in osmo- and ionoregulation. Fish were exposed to water-either freshwater (FW, 10/00) or hypersaline water (saltwater [SW], 450/00)-or air over a moist surface of FW or SW for 9 d and then recovered in water. When fish were emersed for 9 d, (22)Na and (3)H-H(2)O were exchanged across the cutaneous surface. Homeostasis of whole body Cl(-) and water levels but not of Na(+) levels was maintained over 9 d in air. In air-exposed fish, there was a significant increase in the size of skin ionocytes (in SW), a decrease in the number of skin mucous cells (in SW), and an increase in the gill interlamellar cell mass relative to those of fish in water. Gill ionocytes were mostly embedded away from the external surface in air-exposed fish, but the number and size of ionocytes increased (in FW). Interestingly, skin ionocytes formed distinct clusters of 20-30 cells. The estimated number of ionocytes over the whole skin surface was comparable to that in the gills. Overall, the findings support the hypothesis that the skin is a site of osmo- and ionoregulation in K. marmoratus in aquatic and terrestrial environments. Reversible cellular and morphological changes to the skin and gills during air exposure probably enhanced the cutaneous contribution to ion and water balance. PMID- 21029017 TI - AzaSite(r) inhibits Staphylococcus aureus and coagulase-negative Staphylococcus biofilm formation in vitro. AB - PURPOSE: The aim of this study was to analyze the effect of azithromycin (AZM) 1% ophthalmic solution in DuraSite(r) (AzaSite(r)) on biofilm formation by Staphylococcus aureus and coagulase-negative staphylococci in vitro. METHODS: Susceptible and resistant clinical strains (n = 8) of S. aureus and coagulase negative staphylococci were challenged with serial dilutions of AzaSite(r) and its components: AZM, benzalkonium chloride (BAK), and the DuraSite drug delivery vehicle. After 20 h of incubation, bacterial growth was quantified using a spectrophotometer (A = 600 nm). Plates were stained with crystal violet and biofilm formation was quantified spectrophotometrically at A = 590 nm. RESULTS: AzaSite(r) and AZM inhibited bacterial growth (P < 0.05) and biofilm formation (P < 0.05) in AZM-susceptible strains at all studied dilutions. AZM-resistant strains treated with AzaSite(r) exhibited a significant reduction in biofilm formation (P < 0.05) at subinhibitory concentrations (1.25%-5%). AZM had no effect on bacterial growth in resistant strains but conferred a small reduction in biofilm formation at concentrations from 1.25 to 10 mg/mL in most strains. DuraSite(r) inhibited biofilm formation at concentrations between 10% and 2.5% in all studied strains (P < 0.05), without affecting bacterial growth. BAK inhibited bacterial growth and biofilm formation in all strains between concentrations of 0.042 and 0.375 mg/mL (P < 0.05). CONCLUSIONS: AzaSite(r), AZM, or BAK prevented biofilm formation by inhibiting growth of AZM-susceptible strains. AzaSite(r), AZM, and DuraSite(r) also reduced biofilm formation at subinhibitory concentrations for growth. Our data indicate that AZM has a moderate inhibitory effect on biofilm formation, whereas DuraSite(r) appears to play a greater role in the inhibition of staphylococcal biofilm formation by AzaSite(r). PMID- 21029018 TI - A cationic TAT peptide inhibits Herpes simplex virus type 1 infection of human corneal epithelial cells. AB - Abstract Purpose: To determine if a peptide, TAT-Cd(0), inhibits Herpes simplex virus type 1 infection of human corneal epithelial cells. METHODS: TAT-Cd(0) and a control peptide, E(50,51)TAT-Cd(0), were added at various times throughout infection with the lacz-expressing hrR3 virus, and viral replication was measured by beta-galactosidase activity. Toxicity was assessed using a dye reduction assay. RESULTS: The CC(50) value for TAT-Cd(0) was ~100 MUM. In assays with peptide present at all times, TAT-Cd(0) was 150-fold more active than E(50,51)TAT Cd(0) (EC(50) 0.2 vs. 30.0 MUM). The EC(50) values of TAT-Cd(0) for entry inhibition, cell protection, virus inactivation, and inhibition of attachment were 0.1, 0.4, 9.5, and 3.0 MUM, respectively. TAT-Cd(0) was less effective when added 1 h postinfection (EC(50) = 30.0 MUM). CONCLUSIONS: TAT-Cd(0) is an effective inhibitor of Herpes simplex virus type 1 infection in human corneal epithelial cells and affects multiple steps before, or very early, in infection. The peptide has potential as an antiviral and further studies are warranted. PMID- 21029019 TI - Effect of H-7 on secondary cataract after phacoemulsification in the live rabbit eye. AB - PURPOSE: This study is aimed to determine if the serine-threonine kinase inhibitor H-7 inhibits secondary cataract after phacoemulsification in the live rabbit eye. METHODS: Eighteen rabbits underwent extracapsular lens extraction by phacoemulsification in 1 eye. The eye was treated with intravitreal H-7 (300 or 1,200 MUM; n = 6 or 5) or balanced salt solution (BSS) (n = 7) immediately after the surgery and twice weekly for 10 weeks. Each eye received slit lamp biomicroscopy once a week, during which posterior capsule opacification (PCO) was evaluated. The eye was then enucleated and the lens capsule was prepared, fixed, and imaged. PCO was evaluated again on the isolated lens capsule under a phase microscope. Soemmering's ring area (SRA) and the entire lens capsule area were measured from capsule images on a computer and the percentage of SRA (PSRA) in the entire capsule area was calculated. Wet weight of the capsule (WW) was determined on a balance. RESULTS: No significant difference in PCO was observed in any comparison. No significant differences in SRA, PSRA, and WW were observed between the 300 MUM H-7-treated eye and the BSS-treated eye. However, SRA, PSRA, and WW in the 1,200 MUM H-7-treated eye were significantly smaller than those in the BSS-treated eye [28.3 +/- 16.2 vs. 61.4 +/- 8.86 mm(2) (P = 0.001), 33% +/- 20% vs. 65% +/- 15% (P = 0.01), and 65.6 +/- 27.9 vs. 127.0 +/-37.3 mg (P = 0.01)]. CONCLUSIONS: Intravitreal H-7 (1,200 MUM) significantly inhibits Soemmering's ring formation in the live rabbit eye, suggesting that agents that inhibit the actomyosin system in cells may prevent secondary cataract after phacoemulsification. PMID- 21029020 TI - Hyperemia reduction after administration of a fixed combination of bimatoprost and timolol maleate to patients on prostaglandin or prostamide monotherapy. AB - OBJECTIVE: The aim of this study was to evaluate the change in hyperemia and intraocular pressure (IOP) in patients who switch from prostaglandin or prostamide to a fixed combination of prostamide and timolol maleate. DESIGN: A multicenter, longitudinal, noncontrolled, nonrandomized open trial was conducted. PARTICIPANTS: One hundred forty-four patients (282 eyes) were selected: 60 (41.6%) were on travaprost, 51 (35.4%) on bimatoprost, and 33 (22.9%) on latanoprost. All patients included were unable to attain adequate IOP control with monotherapy and had no contraindications to beta-blockers. INTERVENTION: Patients were treated with a fixed combination of bimatoprost and timolol maleate. Hyperemia was evaluated using a referential table, and IOP was measured at 8:00, 12:00, and 16:00 h both before and after 4 months of treatment. MAIN OUTCOME: IOP and hyperemia were compared at 2 time points: pretreatment and after 4 months. The mean of the 3 IOP measurements taken at various points during the day was considered for analysis. Generalized estimating equations were used for repeated measures and intereye dependency adjustments. RESULTS: Hyperemia and IOP were reduced in all 3 groups, with the same pattern for both eyes. The bimatoprost group had the highest levels of hyperemia before treatment when compared with the latanoprost as well as the travaprost group and had the greatest reduction in hyperemia after treatment (P < 0.01). Regarding IOP, all 3 groups had a significant reduction (P < 0.001), but the bimatoprost group had a lower pretreatment IOP when compared with the travaprost and latanoprost groups. CONCLUSION: A significant reduction in hyperemia was found after switching from monotherapy with prostaglandins or prostamide to a fixed combination of prostamide and a beta-blocker. IOP reduction was significant after the intervention in all 3 groups. PMID- 21029021 TI - An Internet-based education program improves breastfeeding knowledge of maternal child healthcare providers. AB - BACKGROUND AND OBJECTIVES: Breastfeeding rates in the United States remain below the Surgeon General's Healthy People 2010 goals. Encouragement of breastfeeding and education by maternal-child healthcare (MCH) providers (physicians, residents, and midlevel providers) improves breastfeeding initiation and duration. Surveys of MCH providers show lack of knowledge about breastfeeding. This study evaluated the effect of usage of "BreastfeedingBasics," a free Internet-based educational course, on the knowledge of MCH providers and evaluation of the baseline knowledge of course users. METHODS: A before and after intervention study was done of MCH providers using the "BreastfeedingBasics" website between 1999 and 2008. Baseline knowledge and change in knowledge were assessed by computer-scored pretests and posttests. RESULTS: Of 3,456 MCH providers enrolled, 2,237 (65%) completed one or more pretest. Total mean pretest/posttest scores were as follows: midlevel providers, 81%/89%; residents, 84%/93%; and physicians, 85%/92% (p < 0.001 among groups and between pretests and posttests). Mean pretest/posttest scores of the modules were as follows: Anatomy/Physiology, 79%/93%; Growth/Development, 72%/91%; Mother-Infant Couple (normal newborn), 82%/92%; and Breastfed Infant with Problems, 77%/91% (p < 0.001 for all). Specific topics with the lowest pretest scores and subsequent posttest scores were as follows (pretest/posttest): supplementation with vitamin D, 61%/93%; breastfeeding physiology, 38%/65%; growth of breastfed infants at 10 days, 80%/95%, 14 days, 72%/91%, and 3-4 months, 39%/84%; and stopping breastfeeding for maternal problems when not indicated, 69%/93% (p < 0.001 for all). CONCLUSIONS: Use of an Internet-based educational program improved knowledge of MCH providers as measured by pretest and posttest scores. Knowledge of the growth of breastfed infants is particularly poor. Increasing knowledge is the first step in improving clinical practice that is necessary for increasing breastfeeding rates and duration. PMID- 21029022 TI - ABM clinical protocol #23: Non-pharmacologic management of procedure-related pain in the breastfeeding infant. AB - A central goal of The Academy of Breastfeeding Medicine is the development of clinical protocols for managing common medical problems that may impact breastfeeding success. These protocols serve only as guidelines for the care of breastfeeding mothers and infants and do not delineate an exclusive course of treatment or serve as standards of medical care. Variations in treatment may be appropriate according to the needs of an individual patient. These guidelines are not intended to be all-inclusive, but to provide a basic framework for physician education regarding breastfeeding. PMID- 21029023 TI - Glove-assisted laparoscopic radical nephrectomy: a novel technique. AB - BACKGROUND: Laparoscopic surgery has not yet met with widespread acceptance due to its degree of technical difficulty. The laparoscopic radical nephrectomy procedure was improved with the aid of an abdominal wall sealing device, a wound retractor, and a surgical glove. METHODS: A 5 cm skin incision was made at the beginning of the operation. The Alexis wound retractor S was set up through this small incision. The wrist portion of the surgical glove (size 8-0) was then used to cover the outer ring of the wound retractor to maintain pneumoperitoneum. The surgeon can use most of the usual surgical instruments through the wound retractor during the laparoscopic surgery. RESULTS: These procedures were successfully conducted in all cases without open conversion, and no postoperative complications were observed. CONCLUSIONS: Glove-assisted laparoscopic surgery can be used to perform advanced laparoscopic procedures. This new technique made laparoscopic abdominal surgery easier and safer for beginners in laparoscopic surgery and skilled surgeons in open surgery. PMID- 21029024 TI - Gasless laparoscopy-assisted surgery for intraabdominal/retroperitoneal tumor of unknown origin: a bridge between total laparoscopic surgery and conventional open surgery. AB - INTRODUCTION: Gasless laparoscopy-assisted surgery has been utilized in many abdominal diseases, and it has been proved to be effective and efficient compared with conventional open surgery. The study was conducted to evaluate the efficacy of gasless laparoscopy-assisted surgery in management of intraabdominal/retroperitoneal tumor of unknown origin. METHODS: From June 2004 to April 2009, nine patients who underwent gasless laparoscopy-assisted surgery for intraabdominal/retroperitoneal tumor of unknown origin were recruited. Intraabdominal/retroperitoneal tumor of unknown origin was defined as (1) diagnosis of enlarged retroperitoneal lymph node; (2) evaluation of peritoneal or mesenteric lesion, or tumor of nondigestive systems; and (3) staging of intraabdominal malignancy. RESULTS: Four patients underwent gasless laparoscopy assisted surgery for retroperitoneal enlarged lymph nodes, four for evaluation of intraabdominal lesion, and two for staging of the malignancy. Sufficient tissue was obtained from all patients, and the diagnosis was as follows: three lymphomas, three peritoneal carcinomatoses, two chronic imflammations, and one benign tumor. CONCLUSIONS: Three purposes can be achieved: a familiar method for the surgeon compared with total laparoscopic surgery, easy accessibility for further oncological management, and intraoperative miniconversion for peritoneal examination. It is a safe and effective way to obtain tissue for pathology and feasible in case of necessary sequential tumor resection. PMID- 21029026 TI - The fading role of T-tube in laparoscopic choledochotomy: primary choledochorrhaphy and over pigtail j and endonasobiliary drainage tubes. AB - BACKGROUND AND AIM: The traditional management of open/laparoscopic choledochotomy after common bile duct (CBD) exploration is accomplished by placement of a T-tube, a procedure historically associated with complications and discomfort. In this study, we share in humble our laparoscopic experience of the use of primary closure of CBD, primary closure over pigtail J, and endonasobiliary drainage (ENBD) tubes as easy and effective alternatives to T tubes. METHODS: From April 2006 to March 2009, 27 (16 women) patients with CBD stones underwent laparoscopic choledochotomy at our institute and were engaged in this study by means of T-tube-free approach after bile duct exploration: primary closure, pigtail J tube, and ENBD tube groups. On admission, routine laboratory and imaging workups were performed to confirm choledocholithiasis diagnosis. RESULTS: The mean operative time for primary closure, pigtail J tube, and ENBD tube groups were 95, 100, and 97.5 minutes, respectively. There was no conversion to open surgery nor was intraoperative complication experienced in all the groups. No major biliary complications such as bile leakage or bile peritonitis were seen; however, 1 patient from the pigtail J group experienced premature tube dislodgement and 1 patient from the ENBD tube group was found with a singular CBD retained stone. CONCLUSIONS: Laparoscopic primary closure of the CBD and over pigtail J and ENBD tubes are easy and effective alternatives to T-tube placements; these procedures are safe and with great feasibility, they offer faster recovery time for patients and early discharge with lower hospital charge. PMID- 21029025 TI - Supraclavicular lateral collar incision versus conventional approach for thyroidectomy: supplement for minimally invasive techniques with extended indications. AB - OBJECTIVE: The indications of various minimally invasive techniques for thyroidetomy are strictly limited to some selected patients; thus, only a minority of the patients can take advantages of them. In this study, we aim at describing a new technique of supraclavicular lateral collar incision for thyroidectomy and to verify the safety and efficacy of it as a beneficial supplement for minimally invasive approach and as a substitute for conventional transverse anterior approach, compared with which the lateral approach demonstrated a better cosmesis and comparative, extended indications. METHODS: A prospective, nonrandomized analysis of consecutive thyroidectomies with different approaches was designed. From May 2006 to April 2009, 98 patients with lateral approach and 136 patients with conventional approach were analyzed to evaluate the eligibility of the new technique and its comparison with conventional approach for various clinical variables. RESULTS: There were no statistical significances between the two groups in terms of age, gender, nodule size, anesthesia, estimated blood loss, operative time, and postoperative complications, whereas there were significant differences in terms of incision length (5.2 +/- 1.04 cm versus 6.9 +/- 1.14 cm, P < 0.001) and cosmetic result (8.7 +/- 0.69 versus 6.7 +/- 0.78, P < 0.001). CONCLUSIONS: The supraclavicular lateral collar incision is a feasible and safe approach for thyroidectomy. Compared with conventional approach, it holds the advantages of comparative extensive indications and similar complication rate but achieving a better cosmetic result. It provides a good alternative beyond conventional thyroidectomy, especially for those previously excluded from minimally invasive techniques. PMID- 21029027 TI - Treatment of diabetes with glucagon-like peptide-1 gene therapy. AB - IMPORTANCE OF THE FIELD: Glucagon-like peptide (GLP)-1 receptor agonists are in widespread clinical use for the treatment of diabetes. While effective, these peptides require frequent injections to maintain efficacy. Therefore, alternative delivery methods including gene therapy are currently being evaluated. AREAS COVERED IN THIS REVIEW: Here, we review the biology of GLP-1, evidence supporting the clinical use of the native peptide as well as synthetic GLP-1 receptor agonists, and the rationale for their delivery by gene therapy. We then review progress made in the field of GLP-1 gene therapy for both type 1 and type 2 diabetes. WHAT THE READER WILL GAIN: Efforts to improve the biological half-life of GLP-1 receptor agonists are discussed. We focus on the development of both viral and non-viral gene delivery methods, highlighting vector designs and the strengths and weaknesses of these approaches. We also discuss the utility of targeting regulated GLP-1 production to tissues including the liver, muscle, islet and gut. TAKE HOME MESSAGE: GLP-1 is a natural peptide possessing several actions that effectively combat diabetes. Current delivery methods for GLP-1 based drugs are cumbersome and do not recapitulate the normal secretion pattern of the native hormone. Gene therapy offers a useful method for directing long term production and secretion of the native peptide. Targeted production of GLP-1 using tissue-specific promoters and delivery methods may improve therapeutic efficacy, while also eliminating the burden of frequent injections. PMID- 21029028 TI - New delivery strategies for the old pentavalent antimonial drugs. AB - IMPORTANCE OF THE FIELD: Pentavalent antimonials are the first-line drugs for treatment of the major tropical disease leishmaniasis. However, their use is limited by the need for daily parenteral administration, their severe side effects and treatment failures. As leishmaniasis belongs to the group of neglected diseases, the improvement of old drugs through new delivery approaches has more support than the development of new chemical entities. AREAS COVERED IN THIS REVIEW: The review covers, from 1977 to the present, the progress achieved towards pharmaceutically acceptable liposome-based formulations of antimonials, identification of specific ligands for improved targeting of infected macrophages and new approaches for oral and topical delivery of antimonial drugs. WHAT THE READER WILL GAIN: Insights into the most promising delivery strategies to improve antimonial therapy and the chemical basis and future directions for achieving innovative orally and topically effective formulations. TAKE HOME MESSAGE: The development of drug delivery strategies for the old pentavalent antimonials is a still growing and promising field, with expected innovations in the near future from improved knowledge of antimony chemistry. PMID- 21029030 TI - Dynamics of microparticles inside lipid vesicles: movement in confined spaces. AB - Microparticles and nanoparticles used in drug delivery frequently depend on their movement in confined spaces such as cells. Liposomes containing small numbers of 1-um diameter polystyrene particles were used to study the dynamics of their movement within the confined space of the liposome interior. The analysis of the trajectories of single and multiple entrapped particles revealed that the particles were largely localized toward the periphery of the liposome with a rare presence in the centre. Interparticle interactions were studied by calculating interparticle distances, ranging from close to zero to around 8 um with a mean of ~4 um. The diffusion coefficient of a single entrapped particle was D = 0.27 * 10(-9) cm(2) s(-1) when compared with 5.1 * 10(-9) cm(2) s(-1) free in water. When more than one particle was entrapped, the calculated diffusion coefficients were D = 0.61 * 10(-9) cm(2) s(-1) for two particles, D = 1.26 * 10(-9) cm(2) s( 1) for three particles, and D = 1.3 * 10(-9) cm(2) s(-1) for multiple particles). Particle movement was found to be distinctly faster at the periphery (average velocity 21.4 MUm s(-)1) than at the centre of the vesicle (average velocity 14.2 MUm s(-1)). These results demonstrate the significance of particle-particle interactions as well as particle-surface interactions, which is evident here in some systems by particle aggregation close to the liposome membrane. PMID- 21029031 TI - Toxicological effects of emission particles from fossil- and biodiesel-fueled diesel engine with and without DOC/POC catalytic converter. AB - There is increasing demand for renewable energy and the use of biodiesel in traffic is a major option when implying this increment. We investigated the toxicological activities of particulate emissions from a nonroad diesel engine, operated with conventional diesel fuel (EN590), and two biodiesels: rapeseed methyl ester (RME) and hydrotreated fresh vegetable oil (HVO). The engine was operated with all fuels either with or without catalyst (DOC/POC). The particulate matter (PM(1)) samples were collected from the dilution tunnel with a high-volume cascade impactor (HVCI). These samples were characterized for ions, elements, and polycyclic aromatic hydrocarbon (PAH) compounds. Mouse RAW264.7 macrophages were exposed to the PM samples for 24 h. Inflammatory mediators, (TNF alpha and MIP-2), cytotoxicity, genotoxicity, and oxidative stress (reactive oxygen species [ROS]) were measured. All the samples displayed mostly dose dependent toxicological activity. EN590 and HVO emission particles had larger inflammatory responses than RME-derived particles. The catalyst somewhat increased the responses per the same mass unit. There were no substantial differences in the cytotoxic responses between the fuels or catalyst use. Genotoxic responses by all the particulate samples were at same level, except weaker for the RME sample with catalyst. Unlike other samples, EN590-derived particles did not significantly increase ROS production. Catalyst increased the oxidative potential of the EN590 and HVO-derived particles, but decreased that with RME. Overall, the use of biodiesel fuels and catalyst decreased the particulate mass emissions compared with the EN590 fuel. Similar studies with different types of diesel engines are needed to assess the potential benefits from biofuel use in engines with modern technologies. PMID- 21029032 TI - Inflammatory markers and exposure to occupational air pollutants. AB - OBJECTIVES: To study the possible relationship between inhalation of airborne particles in the work environment and inflammatory markers in blood. METHODS: Total dust was sampled in the breathing zone of 73 subjects working with welding, cutting, grinding and in foundries such as iron, aluminium, and concrete. Stationary measurements were used to study different size fractions of particles including respirable dust, particulate matter (PM)(10) and PM(2.5), the particle number concentration, the number of particles deposited in the alveoli, and total particle surface area concentration. Inflammatory markers such as interleukin-6 (IL-6), C-reactive protein (CRP), fibrinogen, d-dimer, and urate were measured in plasma or serum before the first shift after the summer vacation and after the first, second, and fourth shift. RESULTS: The mean level of total dust in the breathing zone was 0.93 mg/m(3). The proxies for mean respirable dust fraction was 0.27 mg/m(3), PM(10) 0.60 mg/m(3), and PM(2.5) was 0.31 mg/m(3). The IL-6 values increased by 50% after the first day, but decreased after shift on the second and fourth day. CRP did not increase after the first shift but increased by 17% after the second shift. Other biomarkers were unaffected. A multiple linear regression analysis of a subgroup of 47 subjects showed a statistically significant positive relationship between particle exposure and post-shift IL-6. CONCLUSION: This study supports previous investigations observing increases of IL 6 at air concentrations of PM(10) or PM(2.5) between 0.13 and 0.3 mg/m(3) among healthy subjects. This increase of IL-6 may indicate an increased risk of coronary heart disease. PMID- 21029033 TI - Monitoring the inflammatory potential of exhaust particles from passenger cars in mice. AB - This study presents different research techniques linked together to improve our understanding of the particulate matter (PM) impacts on health. PM samples from the exhaust of different vehicles were collected by a versatile aerosol concentration enrichment system (VACES). Waterborne PM samples were collected with this technique, thus retaining the original physicochemical characteristics of aerosol particles. PM samples originated from a gasoline Euro 3 car and two diesel cars complying with the Euro 2 and Euro 4 standards, respectively. The Euro 2 diesel car operated consecutively on fossil diesel and biodiesel. The Euro 4 car was also retrofitted with a diesel particle filter. In total, five vehicle configurations and an equal number of samples were examined. Each sample was intratracheally instilled to 10 mice at two different dose levels (50 and 100 MUL). The mice were analyzed 24 h after instillation for acute lung inflammation by bronchoalveolar lavage and also for hematological changes. Results show that a moderate but still significant inflammatory response is induced by PM samples, depending on the vehicle. Several organic and inorganic species, including benz(a)anthracene, chrysene, Mn, Fe, Cu, and heavy polycyclic aromatic hydrocarbons (PAHs), as well as the reactive oxygen species content of the PM suspensions are correlated to the observed responses. The study develops conceptual dose-response functions for the different vehicle configurations. These demonstrate that inflammatory response is not directly proportional to the mass dose level of the administered PM and that the relative toxicity potency depends on the dosage level. PMID- 21029034 TI - Stanley (Bob) Davis: An outstanding contribution to drug delivery. PMID- 21029035 TI - Postoperative nausea and vomiting in patients after craniotomy: incidence and risk factors. AB - OBJECT: The purpose of this study was to assess the incidence and risk factors of postoperative nausea and vomiting (PONV) after craniotomy because most available data about PONV in neurosurgical patients are retrospective in nature or derive from small prospective studies. METHODS: Postoperative nausea and vomiting was prospectively assessed within 24 hours after surgery in 229 patients requiring supratentorial or infratentorial craniotomy. To rule out the relevance of the neurosurgical procedure itself to the development of PONV, the observed incidence of vomiting was compared with the rate of vomiting predicted with a surgery independent risk score (Apfel postoperative vomiting score). RESULTS: The overall incidence of PONV after craniotomy was 47%. Logistic regression identified female sex as a risk factor for postoperative nausea (OR 4.25, 95% CI 2.3-7.8) and vomiting (OR 2.62, 95% CI 1.4-4.9). Both the incidence of nausea (OR 3.76, 95% CI 2.06-6.88) and vomiting (OR 4.48, 95% CI 2.4-8.37) were increased in patients not receiving steroids. Postoperative nausea and vomiting occurred after infratentorial as well as after supratentorial procedures. The observed incidence of vomiting within 24 hours after surgery was higher (49%) than would be predicted with the Apfel surgery-independent risk score (31%; p = 0.0004). CONCLUSIONS: The overall incidence of PONV within 24 hours after craniotomy was approximately 50%. One possible reason is that intracranial surgeries pose an additional and independent risk factor for vomiting, especially in female patients. Patients undergoing craniotomy should be identified as high-risk patients for PONV. PMID- 21029036 TI - A transparent artificial dura mater made of silk fibroin as an inhibitor of inflammation in craniotomized rats. AB - OBJECT: To improve the safety of dura repair in neurosurgical procedures, a new dural material derived from silk fibroin was evaluated in a rat model with a dura mater injury. METHODS: The authors prepared new, transparent, artificial dura mater material using silk fibroin from the silkworm, Bombyx mori. The cytotoxic and antiinflammatory effects of the artificial dura mater were examined in vitro and in vivo by histological examination, western blotting, and reverse transcription polymerase chain reaction analyses. RESULTS: The novel artificial dura mater was not cytotoxic. However, it efficiently reduced cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase expression as well as the expression of the proinflammatory cytokines IL-1beta, IL-6, and tumor necrosis factor-alpha. Cerebrospinal fluid leakage did not occur after repair of the brain of craniotomized rats with the artificial dura mater material. CONCLUSIONS: The new artificial dura mater described in this study appears to be safe for application in neurosurgical procedures and can efficiently inhibit inflammation without side effects or CSF leakage. Although the long-term effects of this artificial dura mater material need to be validated in larger animals, the results from this study indicate that it is suitable for application in neurosurgery. PMID- 21029037 TI - The transorbital keyhole approach: early and long-term outcome analysis of approach-related morbidity and cosmetic results. Technical note. AB - OBJECT: In 2003 the authors introduced a minimally invasive transorbital keyhole approach. Because this approach requires removal of the orbital rim and orbital roof, there have been concerns regarding perioperative morbidity, long-term morbidity, and cosmetic results. The authors evaluated approach-related morbidity and cosmetic results in their patients to determine the rate of complications and compared this to published reports of similar approaches. MATERIAL: Seventy-one patients (41 female, 30 male) underwent operations using this approach between 2004 and 2008. Immediate approach-related morbidity was recorded after the operation. Late morbidity was determined after 7 months by an independent examiner while cosmetic results were self-rated by the patient using a questionnaire. RESULTS: Fifty-one (72%) of 71 patients had no postoperative complications and 12 (16.9%) had minor complications, the most common of which was subgaleal CSF collection (7.0%). Other minor complications included facial nerve palsy (2.8%), hyposphagma (2.8%), periorbital swelling due to periorbital hematoma (2.8%), and subdural hematoma (1.4%). Major complications requiring surgical revision occurred in 4 patients (5.6%); these were CSF fistulas in 2 patients, pneumocephalus in 1 patient, and a hematoma in 1 patient. Forty-nine (90.7%) of all 54 examined patients rated the cosmetic results as very good or good. Major long-term morbidity was hyposmia or anosmia (14 patients) followed by hypoesthesia around the scar (9 patients). CONCLUSIONS: The transorbital keyhole approach is a feasible approach with a low-risk profile for postoperative or long term morbidity and excellent cosmetic outcome. PMID- 21029038 TI - Effects of insulin-like growth factor-I and platelet-rich plasma on sciatic nerve crush injury in a rat model. AB - OBJECT: Local administration of insulin-like growth factor-I (IGF-I) has been shown to increase the rate of axon regeneration in crush-injured and freeze injured rat sciatic nerves. Local administration of platelet-rich plasma (PRP) has been also shown to have a measurable effect on facial nerve regeneration after transection in a rat model. The objective of the study was to compare the effects of locally administered IGF-I and PRP on the parameters of the Sciatic Function Index (SFI), sensory function (SF), axon count, and myelin thickness/axon diameter ratio (G-ratio) in a rat model of crush-injured sciatic nerves. METHODS: The right sciatic nerve of Wistar albino rats (24 animals) was crushed using a Yasargil-Phynox aneurysm clip for 45 minutes. All animals were randomly divided into 3 groups: Group 1 (control group) was treated with saline, Group 2 was treated with IGF-I, and Group 3 was treated with PRP. Injections were performed using the tissue expander's injection port with a connecting tube directed at the crush-injured site. Functional recovery was assessed with improvement in the SFI. Recovery of sensory function was using the pinch test. Histopathological examination was performed 3 months after the injury. RESULTS: The SFI showed an improved functional recovery in the IGF-I-treated animals (Group 2) compared with the saline-treated animals (Group 1) 30 days after the injury. In IGF-I-treated rats, sensory function returned to the baseline level significantly faster than in saline-treated and PRP-treated rats as shown in values between SF-2 and SF-7. The G-ratios were found to be significantly higher in both experimental groups than in the control group. CONCLUSIONS: This study suggests that the application of IGF-I to the crush-injured site may expedite the functional recovery of paralyzed muscle by increasing the rate of axon regeneration. PMID- 21029039 TI - A meta-analysis of tumor control rates and treatment-related morbidity for patients with glomus jugulare tumors. AB - OBJECT: Because of the rarity of glomus jugulare tumors, a variety of treatment paradigms are currently used. There is no consensus regarding the optimal management to control tumor burden while minimizing treatment-related morbidity. In this study, the authors assessed data collected from 869 patients with glomus jugulare tumors from the published literature to identify treatment variables that impacted clinical outcomes and tumor control rates. METHODS: A comprehensive search of the English-language literature identified 109 studies that collectively described outcomes for patients with glomus jugulare tumors. Univariate comparisons of demographic information between treatment cohorts were performed to detect differences in the sex distribution, age, and Fisch class of tumors among various treatment modalities. Meta-analyses were performed on calculated rates of recurrence and cranial neuropathy after subtotal resection (STR), gross-total resection (GTR), STR with adjuvant postoperative radiosurgery (STR+SRS), and stereotactic radiosurgery alone (SRS). RESULTS: The authors identified 869 patients who met their inclusion criteria. In these studies, the length of follow-up ranged from 6 to 256 months. Patients treated with STR were observed for 72 +/- 7.9 months and had a tumor control rate of 69% (95% CI 57% 82%). Those who underwent GTR had a follow-up of 88 +/- 5.0 months and a tumor control rate of 86% (95% CI 81%-91%). Those treated with STR+SRS were observed for 96 +/- 4.4 months and had a tumor control rate of 71% (95% CI 53%-83%). Patients undergoing SRS alone had a follow-up of 71 +/- 4.9 months and a tumor control rate of 95% (95% CI 92%-99%). The authors' analysis found that patients undergoing SRS had the lowest rates of recurrence of these 4 cohorts, and therefore, these patients experienced the most favorable rates of tumor control (p < 0.01). Patients who underwent GTR sustained worse rates of cranial nerve (CN) deficits with regard to CNs IX-XI than those who underwent SRS alone; however, the rates of CN XII deficits were comparable. CONCLUSIONS: The authors' analysis is limited by the quality and accuracy of these studies and may reflect source study biases, as it is impossible to control for the quality of the data reported in the literature. Finally, due to the diverse range of data presentation, the authors found that they were limited in their ability to study and control for certain variables. Some of these limitations should be minimized with their use of meta-analysis methods, which statistically evaluate and adjust for between-study heterogeneity. These results provide the impetus to initiate a prospective study, appropriately controlling for variables that can confound the retrospective analyses that largely comprise the existing literature. PMID- 21029040 TI - The supraorbital "keyhole" approach. PMID- 21029041 TI - Central core of the cerebrum. AB - OBJECT: The purpose of this study was to understand 3D relationships of white matter fibers and subcortical areas of gray matter in the central core. METHODS: The lateral and medial aspects of 4 cerebral hemispheres were dissected, applying the fiber dissection technique under the microscope. RESULTS: The central core between the insula and midline includes the extreme, external, and internal capsules; claustrum; putamen; globus pallidus; caudate nucleus; amygdala; diencephalon; substantia innominata; fornix; anterior commissure; mammillothalamic tract; fasciculus retroflexus; thalamic peduncles, including optic and auditory radiations; ansa peduncularis; thalamic fasciculus; and lenticular fasciculus. It is attached to the remainder of the cerebral hemisphere by the cerebral isthmus, which is composed of white matter fibers located between the dorsolateral margin of the caudate nucleus and the full circumference of the circular sulcus of insula. The rostral fibers of the corpus callosum are included in the frontal portion of the cerebral isthmus. CONCLUSIONS: It is very useful for neurosurgeons to facilitate the understanding of spatial relationships and pertinent surgical approaches in and around the central core with a highly complex anatomy by using fiber dissection. PMID- 21029042 TI - Immunohistochemical and quantitative analysis of ghrelin in Syzygium aromaticum. AB - Ghrelin, an endogenous ligand of the growth hormone secretagogue receptor, has been identified in mammals, fish, amphibians, birds, reptiles and some plants. The present investigation was designed to determine whether ghrelin is present in the appetite-stimulating plants Syzygium aromaticum and Salvadora persica, using IHC (immunohistochemistry) to indicate the location of the peptide and ELISA to measure the concentration. ELISA demonstrated that a ghrelin-like substance was present at concentrations of 4070.75+/-664.67 and 75.25+/-24.49 pg/mg in the tissues of flower bud of S. aromaticum and branch of S. persica, respectively. The concentration of ghrelin in human salivary gland tissue was 436.00+/-95.83 pg/mg. Ghrelin was predominantly localized to the T (trachea) and PCs (parenchyma cells) in the flower bud of S. aromaticum. However, no ghrelin immunoreactivity was observed in the PC or T of the branch of S. persica. The evolutionary role of this peptide hormone in plants and animals suggests that they have evolved in a more similar way than previously thought. PMID- 21029043 TI - Chitin hydrolysate stimulates VEGF-C synthesis by MDA-MB-231 breast cancer cells. AB - Up-regulation of VEGF-C (vascular endothelial growth factor C), a most potent lymphangiogenic factor, is associated with inflammation and cancer metastasis. Identification of stimuli contributing to these processes is a challenging task. I demonstrate in this paper that chitin hydrolysate served as a strong inducer of VEGF-C synthesis by human breast cancer MDA-MB-231 cells, increasing the secretion of VEGF-C to the cell culture medium as much as by 10-fold in comparison with the basal production. A moderate increase of VEGF-C secretion was also observed in the presence of hypertonic doses of NaCl, which mimicked the matrix of chitin hydrolysate stock solution, and in the presence of chitin binding lectin, WGA (wheat germ agglutinin). WGA, but not chitin hydrolysate, significantly affected the morphology of cells, which become smaller and rounded as assessed by viewing the actin cytoskeleton. Moreover, chitin hydrolysate inhibited the lectin effect on the cytoskeleton and sustained the overproduction of VEGF-C indicating that WGA-independent receptors were responsible for chitin mediated stimulation of VEGF-C synthesis. These results suggest a novel function of chitin-derived oligosaccharides as VEGF-C stimuli. PMID- 21029044 TI - Molecular mechanisms of substrate recognition and specificity of botulinum neurotoxin serotype F. AB - BoNTs (botulinum neurotoxins) are both deadly neurotoxins and natural toxins that are widely used in protein therapies to treat numerous neurological disorders of dystonia and spinal spasticity. Understanding the mechanism of action and substrate specificity of BoNTs is a prerequisite to develop antitoxin and novel BoNT-derived protein therapy. To date, there is a lack of detailed information with regard to how BoNTs recognize and hydrolyse the substrate VAMP-2 (vesicle associated membrane protein 2), even though it is known to be cleaved by four of the seven BoNT serotypes, B, D, F, G and TeNT (tetanus neurotoxin). In the present study we dissected the molecular mechanisms of VAMP-2 recognition by BoNT serotype F for the first time. The initial substrate recognition was mediated through sequential binding of VAMP-2 to the B1, B2 and B3 pockets in LC/F (light chain of BoNT serotype F), which directed VAMP-2 to the active site of LC/F and stabilized the active site substrate recognition, where the P2, P1' and P2' sites of VAMP-2 were specifically recognized by the S2, S1' and S2' pockets of LC/F to promote substrate hydrolysis. The understanding of the molecular mechanisms of LC/F substrate recognition provides insights into the development of antitoxins and engineering novel BoNTs to optimize current therapy and extend therapeutic interventions. PMID- 21029045 TI - Reduction of N(omega)-hydroxy-L-arginine by the mitochondrial amidoxime reducing component (mARC). AB - NOSs (nitric oxide synthases) catalyse the oxidation of L-arginine to L citrulline and nitric oxide via the intermediate NOHA (N(omega)-hydroxy-L arginine). This intermediate is rapidly converted further, but to a small extent can also be liberated from the active site of NOSs and act as a transportable precursor of nitric oxide or potent physiological inhibitor of arginases. Thus its formation is of enormous importance for the nitric-oxide-generating system. It has also been shown that NOHA is reduced by microsomes and mitochondria to L arginine. In the present study, we show for the first time that both human isoforms of the newly identified mARC (mitochondrial amidoxime reducing component) enhance the rate of reduction of NOHA, in the presence of NADH cytochrome b5 reductase and cytochrome b5, by more than 500-fold. Consequently, these results provide the first hints that mARC might be involved in mitochondrial NOHA reduction and could be of physiological significance in affecting endogenous nitric oxide levels. Possibly, this reduction represents another regulative mechanism in the complex regulation of nitric oxide biosynthesis, considering a mitochondrial NOS has been identified. Moreover, this reduction is not restricted to NOHA since the analogous arginase inhibitor NHAM (N(omega)-hydroxy-N(delta)-methyl-L-arginine) is also reduced by this system. PMID- 21029046 TI - The crystal structure of human GLRX5: iron-sulfur cluster co-ordination, tetrameric assembly and monomer activity. AB - Human GLRX5 (glutaredoxin 5) is an evolutionarily conserved thiol-disulfide oxidoreductase that has a direct role in the maintenance of normal cytosolic and mitochondrial iron homoeostasis, and its expression affects haem biosynthesis and erythropoiesis. We have crystallized the human GLRX5 bound to two [2Fe-2S] clusters and four GSH molecules. The crystal structure revealed a tetrameric organization with the [2Fe-2S] clusters buried in the interior and shielded from the solvent by the conserved beta1-alpha2 loop, Phe69 and the GSH molecules. Each [2Fe-2S] cluster is ligated by the N-terminal activesite cysteine (Cys67) thiols contributed by two protomers and two cysteine thiols from two GSH. The two subunits co-ordinating the cluster are in a more extended conformation compared with iron-sulfur-bound human GLRX2, and the intersubunit interactions are more extensive and involve conserved residues among monothiol GLRXs. Gel-filtration chromatography and analytical ultracentrifugation support a tetrameric organization of holo-GLRX5, whereas the apoprotein is monomeric. MS analyses revealed glutathionylation of the cysteine residues in the absence of the [2Fe 2S] cluster, which would protect them from further oxidation and possibly facilitate cluster transfer/acceptance. Apo-GLRX5 reduced glutathione mixed disulfides with a rate 100 times lower than did GLRX2 and was active as a glutathione-dependent electron donor for mammalian ribonucleotide reductase. PMID- 21029047 TI - Escherichia coli glycogen genes are organized in a single glgBXCAP transcriptional unit possessing an alternative suboperonic promoter within glgC that directs glgAP expression. AB - Although it is generally accepted that Escherichia coli glycogen genes are organized in two tandemly arranged, differentially regulated glgBX and glgCAP operons, RT (reverse transcriptase)-PCR analyses carried out in the present study showed that E. coli cells possess transcripts comprising the five glgBXCAP genes. glg::lacZY expression analyses in cells lacking the region immediately upstream of the glgB gene revealed an almost total abolishment of glgB, glgX and glgC expression, but only a 50-60% reduction of the wild-type glgA and glgP expression levels. Furthermore, similar analyses showed that glgA and glgP expression was almost totally abolished in cells lacking glgA upstream sequences, including glgC, glgB and the asd-glgB intergenic region upstream of glgB. These results indicate that E. coli glgBXCAP genes are organized in a single transcriptional unit controlled by promoter sequences occurring upstream of glgB, and that an alternative suboperonic promoter is located within glgC, driving expression of the glgA and glgP genes. Computer searches for consensus promoters, and analyses of glgB::lacZY and glgA::lacZY expression in cells containing deletions of glgB and glgA upstream sequences identified regions directing glgBXCAP and glgAP expression. 5' RACE (rapid amplification of cDNA ends) analyses located a glgBXCAP transcription start site 155 bp upstream of the glgB initiation codon, and a glgAP transcription start site 359 bp upstream of the glgA initiation codon. Finally, glg::lacZY expression analyses on cells lacking the relA or phoP regulatory genes indicated that both the glgBXCAP operon and the suboperonic promoter driving glgAP expression form part of both the RelA and PhoP-PhoQ regulons. PMID- 21029049 TI - Establishment and characterization of a noradrenergic adrenal chromaffin cell line, tsAM5NE, immortalized with the temperature-sensitive SV40 T-antigen. AB - We established a clonal adrenal medullary cell line, named tsAM5NE, from transgenic mice harbouring the temperature-sensitive Simian virus 40 large T antigen gene, under the control of the tyrosine hydroxylase promoter. tsAM5NE cells conditionally grew at a permissive temperature of 33 degrees C and exhibited the noradrenergic chromaffin cell phenotype. To understand the characteristics of tsAM5NE cells, we first examined the responsiveness of the cells to ligands of the GDNF (glial cell line-derived neurotrophic factor) family. tsAM5NE cells proliferated at the permissive temperature of 33 degrees C in response to either GDNF or neurturin, but not artemin or persephin. At the non permissive temperature of 39 degrees C, GDNF or neurturin caused tsAM5NE cells to differentiate into neuron-like cells; however, the differentiated cells died in a time-dependent manner. Interestingly, LIF (leukaemia inhibitory factor) did not affect the GDNF-mediated cell proliferation at 33 degrees C, but promoted the survival and differentiation of GDNF-treated cells at 39 degrees C. In the presence of GDNF plus LIF, the morphological change induced by the temperature shift was associated with up-regulated expression of neuronal markers, indicating that the cells had indeed undergone neuronal differentiation. Thus, we demonstrated that tsAM5NE cells had the capacity to terminally differentiate into neuron-like cells in response to GDNF plus LIF when the oncogene was inactivated by the temperature shift. Thus, this cell line provides a useful model system for studying the mechanisms regulating neuronal differentiation. PMID- 21029048 TI - Reactive oxygen species derived from Nox4 mediate BMP2 gene transcription and osteoblast differentiation. AB - BMP-2 (bone morphogenetic protein-2) promotes differentiation of osteoblast precursor cells to mature osteoblasts that form healthy bone. In the present study, we demonstrate a novel mechanism of BMP-2-induced osteoblast differentiation. The antioxidant NAC (N-acetyl-L-cysteine) and the flavoprotein enzyme NAD(P)H oxidase inhibitor DPI (diphenyleneiodonium) prevented BMP-2 stimulated alkaline phosphatase expression and mineralized bone nodule formation in mouse 2T3 pre-osteoblasts. BMP-2 elicited a rapid generation of ROS (reactive oxygen species) concomitant with increased activation of NAD(P)H oxidase. NAC and DPI inhibited BMP-2-induced ROS production and NAD(P)H oxidase activity respectively. NAD(P)H oxidases display structurally similar catalytic subunits (Nox1-5) with differential expression in various cells. We demonstrate that 2T3 pre-osteoblasts predominantly express the Nox4 isotype of NAD(P)H oxidase. To extend this finding, we tested the functional effects of Nox4. Adenovirus mediated expression of dominant-negative Nox4 inhibited BMP-2-induced alkaline phosphatase expression. BMP-2 promotes expression of BMP-2 for maintenance of the osteoblast phenotype. NAC and DPI significantly blocked BMP-2-stimulated expression of BMP2 mRNA and protein due to a decrease in BMP2 gene transcription. Dominant-negative Nox4 also mimicked this effect of NAC and DPI. Our results provide the first evidence for a new signalling pathway linking BMP-2-stimulated Nox4-derived physiological ROS to BMP-2 expression and osteoblast differentiation. PMID- 21029050 TI - Butyrylcholinesterase gene mutations in patients with prolonged apnea after succinylcholine for electroconvulsive therapy. AB - BACKGROUND: patients undergoing electroconvulsive therapy (ECT) often receive succinylcholine as part of the anesthetic procedure. The duration of action may be prolonged in patients with genetic variants of the butyrylcholinesterase enzyme (BChE), the most common being the K- and the A-variants. The aim of the study was to assess the clinical significance of genetic variants in butyrylcholinesterase gene (BCHE) in patients with a suspected prolonged duration of action of succinylcholine after ECT. METHODS: a total of 13 patients were referred to the Danish Cholinesterase Research Unit after ECT during 38 months. We determined the BChE activity and the BCHE genotype using molecular genetic methods, the duration of apnea, time to sufficient spontaneous ventilation and whether neuromuscular monitoring was used. The duration of apnea was compared with published data on normal subjects. RESULTS: in 11 patients, mutations were found in the BCHE gene, the K-variant being the most frequent. The duration of apnea was 5-15 min compared with 3-5.3 min from the literature. Severe distress was noted in the recovery phase in two patients. Neuromuscular monitoring was used in two patients. CONCLUSION: eleven of 13 patients with a prolonged duration of action of succinylcholine had mutations in BCHE, indicating that this is the possible reason for a prolonged period of apnea. We recommend objective neuromuscular monitoring during the first ECT. PMID- 21029051 TI - Antipsychotic-associated all-cause and cardiac mortality: what should we worry about and how should the risk be assessed? PMID- 21029052 TI - Initial approach to the hyponatremic patient. AB - Hyponatremia with cerebral symptoms is a medical emergency in which treatment delay may prove fatal. However, controversy prevails over which treatment is the best. This paper presents a practical and unified approach based on a literature study of the physiology of plasma [Na(+) ], the brain's response and clinical and experimental studies. Experimental and clinical studies were thoroughly reviewed. The literature was identified through MESH and free text search in the databases PubMed, Embase and Cochrane, and references in the literature. Cerebral water homeostasis is pivotal in hyponatremia. Prompt, repeated boluses of 2 ml/kg 3% saline constitute a rational treatment of symptomatic hyponatremia. After the initial correction, concern is mainly with avoiding overcorrection and osmotic demyelination. Plasma [Na(+)] is determined by the external balances of water and cations. The water balance must therefore be carefully monitored to counter the dramatic increase in plasma [Na(+)] that may result from brisk diuresis. Definitive treatment of hyponatremia should be directed toward its etiology. This can be challenging and the clinical application of traditional classifications based on hydration is difficult. Therefore, a practical approach is proposed based on the mechanisms of impaired urine dilution. CONCLUSIONS: The conflict between previously opposing standpoints is gradually giving way to an emerging consensus: Prompt bolus treatment of symptomatic hyponatremia with hypertonic saline. After the initial treatment, overcorrection must be avoided. Definitive treatment should be directed toward the nature of the underlying disorder. An approach based on the mechanism governing the impaired urine dilution has been proposed. PMID- 21029053 TI - Evaluating depressive symptoms and their impact on outcome in schizophrenia applying the Calgary Depression Scale. AB - OBJECTIVE: To examine depressive symptoms, their course during treatment, and influence on outcome. METHOD: Weekly Calgary Depression Scale for Schizophrenia ratings were performed in 249 inpatients with schizophrenia. Early response was defined as a 20% reduction in the total score of the Positive and Negative Syndrome Scale for Schizophrenia from admission to week 2, response as a 50% reduction in the total score of the Positive and Negative Syndrome Scale for Schizophrenia (PANSS) from admission to discharge and remission according to the consensus criteria. RESULTS: Thirty six per cent of the patients were depressed at admission, with 23% of them still being depressed at discharge. Depressed patients scored significantly higher on the PANSS negative and general psychopathology subscore, featured more impairments in subjective well-being (P < 0.0001) and functioning (P < 0.0001). They suffered from more suicidality (P = 0.0021), and had greater insight into their illness (P = 0.0105). No significant differences were found regarding early response, response, and remission. CONCLUSION: Patients with depressive symptoms should be monitored closely, given the burden of negative symptoms, their impairments in well-being and functioning and the threat of suicidality. PMID- 21029054 TI - State-of-the-art in longitudinal studies on aging: an overview of the supplement. AB - The articles in this supplement are based on a conference held in January 2008 sponsored by a grant from the Robert Wood Johnson Foundation. The purpose of the conference was to summarize major findings and methodological issues in previous and ongoing longitudinal studies on aging and to identify potentially fruitful areas for future research. This article is a review and synthesis of the articles in this supplement. Each of the articles makes important contributions to summarizing existing research, identifying challenging methodological issues, or proposing areas that should be explored in future research. Three themes were identified: general improvement in the health status of the population aged 65 and older in the United States, a shift in longitudinal research on aging from a focus on the endpoints of disease to a focus on the preclinical stage and underlying mechanisms of these diseases, and contemporary developments in longitudinal research methodology. A number of practical suggestions were also drawn from the articles reviewed. PMID- 21029055 TI - An overview of the design, implementation, and analyses of longitudinal studies on aging. AB - Longitudinal studies have contributed substantially to understanding of aging and geriatric syndromes. These efforts have provided a base of knowledge of the critical factors to consider in designing and implementing new longitudinal studies in older adults. This review highlights some of the major considerations in planning and implementing this type of study. Longitudinal studies can assess change over time and specific disease endpoints. Such projects require multidisciplinary teams with expertise in the many health and contextual factors that must be considered. Recent advances in study design include the use of imaging and biomarkers to assess mechanisms and approaches that raise the ceiling on measurement and integrate assessment of exposures over time. Study implementation requires careful planning and monitoring to maintain fidelity to the scientific goals. Analysis of longitudinal data requires approaches that account for inevitable missing data. New studies should take advantage of the experience obtained from longitudinal studies on aging already conducted. PMID- 21029056 TI - A review of selected longitudinal studies on aging: past findings and future directions. AB - A review of the 51 longitudinal aging studies currently in the National Institute on Aging Database of Longitudinal Studies was conducted to identify major information gaps and areas for future research. Database information, which included posted study summaries, study details from principal investigators or directors of these projects, and more than 300 recent publications based on the studies, were reviewed to identify significant findings of each study. This review summarizes the main findings and identifies the need for future work within six broad study topics: cognitive function, socioeconomic status, health and physical performance, morbidity and mortality predictors, healthcare costs, and genetics. The percentages of these 51 studies addressing the four most common topics are as follows: cognitive function (44%), health and physical performance (51%), socioeconomic factors (55%), and predictors of morbidity/mortality (63%). Important areas not addressed to any major degree were healthcare costs and genetics. Only two studies reported findings on genetics or epigenetics of human aging, and only a single study reported on associations between aging and financial costs, especially healthcare costs, which have been postulated to be important determinants of care and life quality. The results of this review, together with the specific directions proposed by other investigators with longitudinal study expertise, will inform the strategic planning of future long term studies of aging. PMID- 21029057 TI - Predictive health: the imminent revolution in health care. AB - Increasing social, economic, and political pressures to reform the U.S. approach to medical care makes change likely. A fundamental premise of predictive health is that it should be cheaper (at least per person life-year) and more efficient and have a greater return on the investment of keeping people healthy as opposed to waiting for disease to intervene. The Emory Predictive Health and Society Strategic Initiative and its Center for Health Discovery and Well Being have embarked on a program to define health to the extent that modern science permits in the context of the entire human experience, to identify measurable variables that describe and predict a healthy state, and to use that knowledge to design health-focused interventions that are affordable and effective. Initial results from a study of a randomly selected "essentially healthy" cohort, using extensive assessments and a health partner, are promising. Studies of healthy aging over the entire life spectrum promise valuable normative data for age-specific assessments of health and the setting of realistic health goals. PMID- 21029058 TI - A road map for the recruitment and retention of older adult participants for longitudinal studies. AB - Cost-effective recruitment of older adult study participants is essential to geriatric research. Because this age group is particularly challenging to recruit, careful planning and ongoing evaluation is important for successful participant recruitment and retention. Experienced recruitment staff should be involved in a study from the earliest planning stages through the active recruitment phase to the last randomization or enrollment visit. A number of participant burdens are unique to the elderly population. Recruitment staff should be trained to understand and assist with the needs of older research volunteers. Addressing these unique participant burdens can ensure successful study participant recruitment and retention in ongoing and future longitudinal studies on aging. PMID- 21029059 TI - Assessment of function and disability in longitudinal studies. AB - Over the past 2 decades, there has been considerable progress in the assessment of function and disability in older persons. Tests of physical performance are now routinely included in longitudinal studies to measure functional limitations, which are considered the building blocks of functioning. In addition, new strategies have been developed to assess the presence and onset of disability and to expand the scope of disability assessments beyond traditional indicators of difficulty and dependence. Contemporary measurement technologies, such as item response theory and computer adaptive testing, show great promise in the assessment of functional status and disability, but prospective studies are needed to demonstrate their true value, particularly to identify the circumstances in which their use will improve the assessment of functional outcomes in older persons. Another high priority for future research is to validate and further refine strategies to more completely and accurately ascertain the occurrence of disability in older persons. PMID- 21029061 TI - The aging mind: vascular health in normal cognitive aging. AB - In spite of the breakneck speed at which understanding of the biological basis of the aging process has evolved, the important determinants of aging and longevity have yet to be uncovered. The preservation of cognitive functioning is an essential component of successful aging, and the ability to distinguish those who maintain cognitive health into advanced age from those who experience cognitive decline may influence public health efforts to prevent or delay the onset of cognitive impairment in old age. There is growing evidence implicating vascular risk factors and related subclinical cerebrovascular damage in cognitive impairment and dementia, but Alzheimer's disease is highly prevalent in older populations, and the role of inflammation in vascular and neurodegenerative processes is poorly understood. There is a growing need to examine the effects of these factors on normal cognitive aging. This brief survey of the literature reviews evidence of the roles of subclinical vascular brain damage and exposure to cerebrovascular risk factors in normal cognitive aging. PMID- 21029060 TI - Modeling cognitive trajectories within longitudinal studies: a focus on older adults. AB - The natural history of life span cognitive performance and its late-life determinants have been studied from an array of perspectives. Significant insights come from psychological disciplines, including cognitive, developmental, and neuropsychology, as well as from medical specialties, such as geriatrics, neurology, psychiatry, neuroradiology, and neuropathology, that contribute to the growing interdisciplinary scientific field: cognitive neuroscience of aging. This survey of longitudinal studies of aging suggests that disease-oriented investigations commonly do not adequately consider normative cognitive changes, whereas developmental studies do not sufficiently measure and model nonnormative cognitive aging. This article argues for an integrative perspective that considers both of these influences on cognitive trajectories and presents a series of methodological concerns that have not been addressed comprehensively. Interdisciplinary methods from longitudinal observational studies should be leveraged to enable translational interventions to promote brain longevity. PMID- 21029062 TI - Influence of age and health behaviors on stroke risk: lessons from longitudinal studies. AB - Stroke is a major cause of death and serious neurological disability in older adults in the United States today. The most effective means available for reducing the burden of stroke involves risk factor modification. Given the growing number of older adults at risk for stroke, it is increasingly important to identify health behaviors that can produce significant change. Ongoing longitudinal studies have identified several behavioral factors that have been shown to improve overall health and reduce the risk of stroke, including effective management of hypertension, cessation of cigarette smoking for those who smoke, and maintaining a healthy diet and active physical lifestyle. Because modification of risk factors remains a primary intervention for effective prevention of stroke, community-based studies that address and institute stroke prevention strategies have the best opportunity to reduce or postpone the devastating effect of stroke. PMID- 21029063 TI - The energetic pathway to mobility loss: an emerging new framework for longitudinal studies on aging. AB - The capacity to walk independently is a central component of independent living. Numerous large and well-designed longitudinal studies have shown that gait speed, a reliable marker of mobility, tends to decline with age and as a consequence of chronic disease. This decline in performance is of utmost importance because slow walking speed is a strong, independent predictor of disability, healthcare utilization, nursing home admission, and mortality. Based on these robust findings, it has been postulated that age-associated decline in walking speed is a reliable barometer of the effect of biological aging on health and functional status. Despite the extraordinary prognostic information that walking speed provides, which is often superior to traditional medical information, there is a limited understanding of the mechanisms that underlie age- and disease-related gait speed decline. Identifying the mechanisms that underlie the prognostic value of walking speed should be a central theme in the design of the next generation of longitudinal studies of aging, with appropriate measures introduced and analytical approaches incorporated. This study hypothesized that a scarcity of available energy induces the decline in customary walking speed with aging and disease. Based on work in the Baltimore Longitudinal Study of Aging, examples of measures, operationalized dimensions, and analytical models that may be implemented to address this are provided. The main premise is simple: the biochemical processes that maintain life, secure homeostatic equilibrium, and prevent the collapse of health require energy. If energy becomes deficient, adaptive behaviors develop to conserve energy. PMID- 21029065 TI - Missing data? Plan on it! AB - Longitudinal study designs are indispensable for investigating age-related functional change. There now are well-established methods for addressing missing data in longitudinal studies. Modern missing data methods not only minimize most problems associated with missing data (e.g., loss of power and biased parameter estimates), but also have valuable new applications such as research designs that use modern missing data methods to plan missing data purposefully. This article describes two state-of-the-art statistical methodologies for addressing missing data in longitudinal research: growth curve analysis and statistical measurement models. How the purposeful planning of missing data in research designs can reduce subject burden, improve data quality and statistical power, and manage costs is then described. PMID- 21029064 TI - Translating research to promote healthy aging: the complementary role of longitudinal studies and clinical trials. AB - An important challenge in epidemiology is the difficulty in inferring causality from observational studies. Even the best longitudinal studies have limitations in this regard, and when clinical trials are feasible, they will provide more definite evidence of causality, but even when clinical trials are feasible, a large amount can be learned about the disease process, assessment techniques, subject selection criteria, and the effect of potential interventions from longitudinal studies. This review covers the theoretical issues supporting the value and limitations of longitudinal studies, the practical utilization in clinical trials of different aspects of knowledge that can be gained from longitudinal studies, critical issues in the translation of longitudinal observational studies into clinical trials, and the value of observational studies in broadening the applicability of specific trials. Relevant issues are illustrated with examples of unsuccessful and successful trials, with a major emphasis on clinical trials of physical activity in older persons. PMID- 21029066 TI - A 120-year-old clinical challenge. PMID- 21029068 TI - Microangiopathic haemolytic anaemia and hyposplenism in angiosarcoma. PMID- 21029069 TI - Multiple unit umbilical cord blood transplantation with total body irradiation, etoposide and antithymocyte globulin for adult haematological malignancy patients. PMID- 21029070 TI - Daunorubicin-induced hyperpigmentation. PMID- 21029071 TI - Suboptimal response to imatinib according to 2006-2009 European LeukaemiaNet criteria: a 'grey zone' at 3, 6 and 12 months identifies chronic myeloid leukaemia patients who need early intervention. PMID- 21029073 TI - Deleterious mutation in GPSM2 identified as cause for nonsyndromic deafness. PMID- 21029072 TI - Effect of immunoglobulin G (IgG) interchain disulfide bond cleavage on efficacy of intravenous immunoglobulin for immune thrombocytopenic purpura (ITP). AB - Intravenous immunoglobulin (IVIG) has been used widely to treat immune thrombocytopenic purpura (ITP), but the mechanisms of its action remain unclear. We investigated the affinity for Fcgamma receptors (FcgammaRs) and the thrombocytopenia-ameliorating effect of S-sulfonated gammaglobulin (SGG) and S alkylated gammaglobulin (AGG), in comparison with unmodified gammaglobulin (GG), in a mouse ITP model. Cleavage of immunoglobulin (Ig)G interchain disulfide bonds by either S-sulfonation or S-alkylation did not decrease the affinity for FcgammaRIIA (CD32A) and FcgammaRIIB (CD32B), but did decrease the affinity for FcgammaRIA (CD64A) and FcgammaRIIIA (CD16A), presumably because of changes in H chain configuration. The interchain disulfide bond cleavage decreased the affinity much more for mouse FcgammaRIV than for mouse FcgammaRIIB. The ability of AGG to ameliorate ITP was greatly diminished, while SGG, whose disulfide bonds are reconstituted in vivo, was as effective as GG. These results suggest that the interchain disulfide bonds are important for therapeutic effect. It is also suggested that the interaction of IVIG with the inhibitory receptor FcgammaRIIB is insufficient for effective amelioration of ITP and that, at least in this model, direct binding of IVIG to FcgammaRIIIA is also required. PMID- 21029074 TI - TMEM216 joins its ciliary cousins in ciliopathies. PMID- 21029075 TI - Cognitive deficits in Down syndrome: narrowing 'Down' to Olig1 and Olig2. PMID- 21029076 TI - Genome structure and the benefit of sex. AB - We examine the behavior of sexual and asexual populations in modular multipeaked fitness landscapes and show that sexuals can systematically reach different, higher fitness adaptive peaks than asexuals. Whereas asexuals must move against selection to escape local optima, sexuals reach higher fitness peaks reliably because they create specific genetic variants that "skip over" fitness valleys, moving from peak to peak in the fitness landscape. This occurs because recombination can supply combinations of mutations in functional composites or "modules," that may include individually deleterious mutations. Thus when a beneficial module is substituted for another less-fit module by sexual recombination it provides a genetic variant that would require either several specific simultaneous mutations in an asexual population or a sequence of individual mutations some of which would be selected against. This effect requires modular genomes, such that subsets of strongly epistatic mutations are tightly physically linked. We argue that such a structure is provided simply by virtue of the fact that genomes contain many genes each containing many strongly epistatic nucleotides. We briefly discuss the connections with "building blocks" in the evolutionary computation literature. We conclude that there are conditions in which sexuals can systematically evolve high-fitness genotypes that are essentially unevolvable for asexuals. PMID- 21029077 TI - Contagious parthenogenesis, automixis, and a sex determination meltdown. AB - Because of the twofold cost of sex, genes conferring asexual reproduction are expected to spread rapidly in sexual populations. However, in reality this simple prediction is often confounded by several complications observed in natural systems. Motivated by recent findings in the Cape honey bee and in the parasitoid wasp Lysiphlebus fabarum, we explore through mathematical models the spread of a recessive, parthenogenesis inducing allele in a haplodiploid population. The focus of these models is on the intricate interactions between the mode of parthenogenesis induction through automixis and complementary sex determination (CSD) systems. These interactions may result in asexual production of diploid male offspring and the spread of the parthenogenesis-inducing allele through these males. We demonstrate that if parthenogenetic females produce a substantial proportion of male offspring, this may prevent the parthenogenesis-inducing allele from spreading. However, this effect is weakened if these diploid males are at least partially fertile. We also predict a degradation of multilocus CSD systems during the spread of parthenogenesis, following which only a single polymorphic CSD locus is maintained. Finally, based on empirical parameter estimates from L. fabarum we predict that male production in parthenogens is unlikely to prevent the eventual loss of sexual reproduction in this system. PMID- 21029078 TI - Partial resistance in the Linum-Melampsora host-pathogen system: does partial resistance make the red queen run slower? AB - Five levels of disease expression were scored in a cross-inoculation study of 120 host and 60 pathogen lines of wild flax Linum marginale and its rust fungus Melampsora lini sampled from six natural populations. Patterns of partial resistance showed clear evidence of gene-for-gene interactions, with particular levels of partial resistance occurring in specific host-pathogen combinations. Sympatric and putatively more highly coevolved host-pathogen combinations had a lower frequency of partial resistance types relative to allopatric combinations. Sympatric host-pathogen combinations also showed a lower diversity of resistance responses, but there was a trend toward a greater fraction of this variance being determined by pathogen-genotype * host-genotype interactions. In this system, there was no evidence that partial resistances slow host-pathogen coevolution. The analyses show that if variation is generated by among population host or pathogen dispersal, then coevolution occurs largely by pathogens overcoming the partial resistances that are generated. PMID- 21029079 TI - Genomic imprinting and conflict-induced decanalization. AB - Genomic imprinting is the phenomenon in which the expression pattern of an allele depends on its parental origin. When maternally expressed and paternally expressed imprinted loci affect the same trait, the result is an arms race, with each locus under selection to increase its level of expression. This article develops a model of the deleterious consequences of this escalation, deriving from an increase in the variance in gene expression level, and resulting increase in phenotypic variance in the population. This phenomenon is referred to here as "conflict-induced decanalization." Modifiers that canalize gene expression are selectively favored, but these induce further escalation from both loci, resulting in a net increase in phenotypic variance and a reduction in population mean fitness. This results in a feedback loop, where increasing canalization of gene expression leads to increasing decanalization of the phenotype. This phenomenon may explain the surprisingly high frequency of certain diseases. Disorders to which this decanalization process might contribute include growth- and metabolism-related phenomena such as preterm birth, as well as certain major psychiatric disorders, including schizophrenia and autism. PMID- 21029080 TI - The evolution and suppression of male suicide under paternal genome elimination. AB - Different genetic systems can be both the cause and the consequence of genetic conflict over the transmission of genes, obscuring their evolutionary origin. For instance, with paternal genome elimination (PGE), found in some insects and mites, both sexes develop from fertilized eggs, but in males the paternally derived chromosomes are either lost (embryonic PGE) or deactivated (germline PGE) during embryogenesis and not transmitted to the next generation. Evolution of germline PGE requires two transitions: (1) elimination of the paternal genome during spermatogenesis; (2) deactivation of the paternal genome early in development. Hypotheses for the evolution of PGE have mainly focused on the first transition. However, maternal genes seem to be responsible for the deactivation and here we investigate if maternal suppression could have evolved in response to paternally expressed male suicide genes. We show that sibling competition can cause such genes to spread quickly and that inbreeding is necessary to prevent fixation of male suicide, and subsequent population extinction. Once male-suicide has evolved, maternally expressed suppressor genes can invade in the population. Our results highlight the rich opportunity for genetic conflict in asymmetric genetic systems and the counterintuitive phenotypes that can evolve as a result. PMID- 21029081 TI - Pain perception studies in tension-type headache. AB - Tension-type headache (TTH) is a disorder with high prevalence and significant impact on society. Understanding of pathophysiology of TTH is paramount for development of effective treatments and prevention of chronification of TTH. Our aim was to review the findings from pain perception studies of pathophysiology of TTH as well as to review the research of pathophysiology of TTH. Pain perception studies such as measurement of muscle tenderness, pain detection thresholds, pain tolerance thresholds, pain response to suprathreshold stimulation, temporal summation and diffuse noxious inhibitory control (DNIC) have played a central role in elucidating the pathophysiology of TTH. It has been demonstrated that continuous nociceptive input from peripheral myofascial structures may induce central sensitization and thereby chronification of the headache. Measurements of pain tolerance thresholds and suprathreshold stimulation have shown presence of generalized hyperalgesia in chronic tension-type headache (CTTH) patients, while DNIC function has been shown to be reduced in CTTH. One imaging study showed loss of gray matter structures involved in pain processing in CTTH patients. Future studies should aim to integrate pain perception and imaging to confirm this finding. Pharmacological studies have shown that drugs like tricyclic anti depressant amitriptyline and nitric oxide synthase inhibitors can reverse central sensitization and the chronicity of headache. Finally, low frequency electrical stimulation has been shown to rapidly reverse central sensitization and may be a new modality in treatment of CTTH and other chronic pain disorders. PMID- 21029082 TI - Newer forms of unclassified headaches. PMID- 21029083 TI - Health-related quality of life, disability and severity of disease in patients with migraine attending to a specialty headache center. AB - BACKGROUND: The impact of migraine on patients' daily life has been evaluated in several studies. The relationship between disability and health-related quality of life (HRQoL) in patients with migraine, however, has not been systematically evaluated. OBJECTIVE: To assess the impact of migraine on patients' HRQoL and disability patterns and to describe the relationship between disability and HRQoL in patients with migraine attending a specialty Italian headache center according to the biopsychosocial model of disability endorsed by the International Classification of Functioning, Disability and Health. METHODS: In this observational study, adult patients with migraine were consecutively recruited. Disability was measured with the MIDAS (Migraine Disability Assessment) and the WHO-DAS II (World Health Organization Disability Assessment Schedule), HRQoL with the SF-36 (Medical Outcome Survey 36-item Short-Form Health Survey). Spearman's rank correlation between MIDAS score, SF-36 and WHO-DAS II scales was performed to evaluate the relationships between quality of life and disability. The impact of migraine on disability and HRQoL was assessed by comparing WHO-DAS II and SF 36 scores against Italian normative values, and by evaluating the different disability and HRQoL profiles in patients with different severity of migraine, defined according to migraine frequency and pain intensity. RESULTS: A total of 102 patients with migraine (87 females) were enrolled. Mild to moderate correlations were reported between WHO-DAS II and SF-36's PCS (r = -0.67, P < .01) and MCS (r = -0.36, P < .05) scales; MIDAS score correlations to SF-36's PCS (r = -0.44, P < .01) and MCS (not significant) were lower than WHO-DAS II summary score. The correlation between MIDAS score and the WHO-DAS II summary score was mild (r = -0.36, P < .05). The majority of HRQoL and disability scales (with the exception of SF-36's Physical Functioning, and WHO-DAS II Getting along with people scales) scored significantly lower than normative values. A trend towards worsening of both HRQoL and disability, consistent with increasing migraine severity, was reported (Mann-Whitney's U = 119.5 for MIDAS; U= 113.0 for WHO-DAS II summary score, both with P < .01; U = 152.9 for PCS; U = 171.0 for MCS, both with P< .05) CONCLUSIONS: In migraineurs attending an Italian specialty headache clinic, disability scores were worse and HRQoL scores lower than those of the general population, and worsened consistently with increased migraine severity. Measures of HRQoL and disability evaluate different psychosocial aspects of migraine and researchers should continue to employ them in public health and clinical research on migraine. They provide information on a poorly recognized part of migraine's burden, where economic impact is minimal but there are important effects on patients' daily lives in terms of interpersonal relationships, perceived quality of life and emotional status. PMID- 21029084 TI - Coverage and preventive screening. AB - CONTEXT: Preventive care has been shown as a high-value health care service. Many employers now offer expanded coverage of preventive care to encourage utilization. OBJECTIVE: To determine whether expanding coverage is an effective means to encourage utilization. DESIGN: Comparison of screening rates before and after introduction of deductible-free coverage. SETTING: People insured through large corporations between 2002 and 2006. PATIENTS OR OTHER PARTICIPANTS: Preferred Provider Organization (PPO) enrollees from an employer introducing deductible-free coverage, and a control group enrolled in a PPO from a second employer with no policy change. MAIN OUTCOME MEASURES: Adjusted probability of endoscopy, fecal occult blood test (FOBT), lipid screens, mammography, and Papanicolaou (pap) smears. INTERVENTION: Introduction of first-dollar coverage (FDC) of preventive services in 2003. RESULTS: After adjusting for demographics and secular trends, there were between 23 and 78 additional uses per 1,000 eligible patients of covered preventive screens (lipid screens, pap smears, mammograms, and FOBT), with no significant changes in the control group or in a service without FDC (endoscopy). CONCLUSIONS: FDC improves utilization modestly among healthy individuals, particularly those in lower deductible plans. Compliance with guidelines can be encouraged by lowering out-of-pocket costs, but patients' predisposing characteristics merit attention. PMID- 21029085 TI - Incremental cost of postacute care in nursing homes. AB - OBJECTIVES: To determine whether the case mix index (CMI) based on the 53 Resource Utilization Groups (RUGs) captures all the cross-sectional variation in nursing home (NH) costs or whether NHs that have a higher percent of Medicare skilled care days (%SKILLED) have additional costs. DATA AND SAMPLE: Nine hundred and eighty-eight NHs in California in 2005. Data are from Medicaid cost reports, the Minimum Data Set, and the Economic Census. RESEARCH DESIGN: We estimate hybrid cost functions, which include in addition to outputs, case mix, ownership, wages, and %SKILLED. Two-stage least-square (2SLS) analysis was used to deal with the potential endogeneity of %SKILLED and CMI. RESULTS: On average 11 percent of NHs days were due to skilled care. Based on the 2SLS model, %SKILLED is associated with costs even when controlling for CMI. The marginal cost of a one percentage point increase in %SKILLED is estimated at U.S.$70,474 or about 1.2 percent of annual costs for the average cost facility. Subanalyses show that the increase in costs is mainly due to additional expenses for nontherapy ancillaries and rehabilitation. CONCLUSION: The 53-RUGs case mix does not account completely for all the variation in actual costs of care for postacute patients in NHs. PMID- 21029086 TI - Effects of competition on the cost and quality of inpatient rehabilitation care under prospective payment. AB - OBJECTIVE: To determine the effect of competition in postacute care (PAC) markets on resource intensity and outcomes of care in inpatient rehabilitation facilities (IRFs) after prospective payment was implemented. DATA SOURCES: Medicare claims, Provider of Services file, Enrollment file, Area Resource file, Minimum Data Set. STUDY DESIGN: We created an exogenous measure of competition based on patient travel distances and used instrumental variables models to estimate the effect of competition on inpatient rehabilitation costs, length of stay, and death or institutionalization. DATA EXTRACTION METHODS: A file was constructed linking data for Medicare patients discharged from acute care between 2002 and 2003 and admitted to an IRF with a diagnosis of hip fracture or stroke. PRINCIPAL FINDINGS: Competition had different effects on treatment intensity and outcomes for hip fracture and stroke patients. In the treatment of hip fracture, competition increased costs and length of stay, while increasing rates of death or institutionalization. In the treatment of stroke, competition decreased costs and length of stay and produced inferior outcomes. CONCLUSIONS: The effects of competition in PAC markets may vary by condition. It is important to study the effects of competition by diagnostic condition and to study the effects across populations that vary in severity. Our finding that higher competition under prospective payment led to worse IRF outcomes raises concerns and calls for additional research. PMID- 21029087 TI - Impact of high-deductible health plans on health care utilization and costs. AB - BACKGROUND: High-deductible health plans (HDHPs) are of high interest to employers, policy makers, and insurers because of potential benefits and risks of this fundamentally new coverage model. OBJECTIVE: To investigate the impact of HDHPs on health care utilization and costs in a heterogeneous group of enrollees from a variety of individual and employer-based health plans. DATA: Claims and member data from a major insurer and zip code-level census data. STUDY DESIGN: Retrospective difference-in-differences analyses were used to examine the impact of HDHP plans. This analytical approach compared changes in utilization and expenditures over time (2007 versus 2005) across the two comparison groups (HDHP switchers versus matched PPO controls). RESULTS: In two-part models, HDHP enrollment was associated with reduced emergency room use, increases in prescription medication use, and no change in overall outpatient expenditures. The impact of HDHPs on utilization differed by subgroup. Chronically ill enrollees and those who clearly had a choice of plans were more likely to increase utilization in specific categories after switching to an HDHP plan. CONCLUSIONS: Whether HDHPs are associated with lower costs is far from settled. Various subgroups of enrollees may choose HDHPs for different reasons and react differently to plan incentives. PMID- 21029088 TI - Do hospitals alter patient care effort allocations under pay-for-performance? AB - OBJECTIVE: To determine whether hospitals increase efforts on easy tasks relative to difficult tasks to improve scores under pay-for-performance (P4P) incentives. DATA SOURCE: The Centers for Medicare and Medicaid Services Hospital Compare data from Fiscal Years 2003 through 2005 and 2003 American Hospital Association Annual Survey data. STUDY DESIGN: We classified measures of process compliance targeted by the Premier Hospital Quality Incentive Demonstration as easy or difficult to improve based on whether they introduce additional per-patient costs. We compared process compliance on easy and difficult tasks at hospitals eligible for P4P bonus payments relative to hospitals engaged in public reporting using random effects regression models. PRINCIPAL FINDINGS: P4P hospitals did not preferentially increase efforts for easy tasks in patients with heart failure or pneumonia, but they did exhibit modestly greater effort on easy tasks for heart attack admissions. There is no systematic evidence that effort was allocated toward easier processes of care and away from more difficult tasks. CONCLUSIONS: Despite perverse P4P incentives to change allocation of efforts across tasks to maximize performance scores at lowest cost, we find little evidence that hospitals respond to P4P incentives as hypothesized. Alternative incentive structures may motivate greater response by targeted hospitals. PMID- 21029089 TI - Counting uninsurance and means-tested coverage in the American community survey: a comparison to the current population survey. AB - OBJECTIVE: To compare health insurance coverage estimates from the American Community Survey (ACS) to the Current Population Survey (CPS-ASEC). DATA SOURCES/STUDY SETTING: The 2008 ACS and CPS-ASEC, 2009. STUDY DESIGN: We compare age-specific national rates for all coverage types and state-level rates of uninsurance and means-tested coverage. We assess differences using t-tests and p values, which are reported at <.05, <.01, and <.001. An F-test determines whether differences significantly varied by state. PRINCIPAL FINDINGS: Despite substantial design differences, we find only modest differences in coverage estimates between the surveys. National direct purchase and state-level means tested coverage levels for children show the largest differences. CONCLUSIONS: We suggest that the ACS is well poised to become a useful tool to health services researchers and policy analysts, but that further study is needed to identify sources of error and to quantify its bias. PMID- 21029090 TI - The residential history file: studying nursing home residents' long-term care histories(*). AB - OBJECTIVE: To construct a data tool, the Residential History File (RHF), that summarizes information from Medicare claims and nursing home (NH) Minimum Data Set (MDS) assessments to track people through health care locations, including non-Medicare-paid NH stays. DATA SOURCES: Online Survey of Certification and Reporting (OSCAR) data for 202 free-standing NHs, Medicare Denominator, claims (parts A and B), and MDS assessments for 60,984 people who were present in one of these NHs in 2006. METHODS: The algorithm creating the RHF is outlined and the RHF for the study data are used to describe place of death. The identification of residents in NHs is compared with the reports in OSCAR and part B claims. PRINCIPAL FINDINGS: The RHF correctly identified 84.8 percent of part B claims with place-of-service in NH, and it identified 18.3 less residents on average than reported in the OSCAR on the day of the survey. The RHF indicated that 17.5 percent non-Medicare NH decedents were transferred to the hospital to die versus 45.6 percent skilled nursing facility decedents. CONCLUSIONS: The population based design of the RHF makes it possible to conduct policy-relevant research to examine the variation in the rate and type of health care transitions across the United States. PMID- 21029091 TI - HIV-related avoidance and universal precaution in medical settings: opportunities to intervene. AB - OBJECTIVE: To determine the association between adherence to universal precaution (UP) and avoidance attitudes toward patients living with HIV/AIDS (PLH) among service providers. DATA SOURCES/SETTING: A total of 1,760 health service providers were randomly selected from 40 county hospitals in two provinces of China. STUDY DESIGN: A self-administered questionnaire was used to collect demographic characteristics, UP knowledge and training, UP adherence, availability of UP supplies at work, and avoidance attitudes toward PLH in a cross-sectional survey. DATA ANALYSIS: A series of regression models were used to examine associations among the UP-related factors and their relationship to avoidance attitudes toward PLH. PRINCIPAL FINDINGS: UP training was associated with better knowledge of and adherence to UP and perceived availability of UP supplies in hospitals. UP training, knowledge, and adherence were significantly associated with avoidance attitudes toward PLH in medical practice. Being a nurse was also related to HIV-related avoidance. CONCLUSION: UP promotion campaigns, including in-service training and reinforcement of UP adherence, could play an important role in the battle against HIV-related avoidance in medical settings. Intervention programs should focus on not only individual providers' attitudes and behaviors but also on structural support for norms shifts in the medical community. PMID- 21029092 TI - Channeling consumers to preferred providers and the impact of status quo bias: does type of provider matter? AB - CONTEXT: To effectively bargain about the price and quality of health services, health insurers need to successfully channel their enrollees. Little is known about consumer sensitivity to different channeling incentives. In particular, the impact of status quo bias, which is expected to differ between different provider types, can play a large role in insurers' channeling ability. OBJECTIVE: To examine consumer sensitivity to channeling strategies and to analyze the impact of status quo bias for different provider types. DATA SOURCES/STUDY DESIGN: With a large-scale discrete choice experiment, we investigate the impact of channeling incentives on choices for pharmacies and general practitioners (GPs). Survey data were obtained among a representative Dutch household panel (n = 2,500). PRINCIPAL FINDINGS: Negative financial incentives have a two to three times larger impact on provider choice than positive ones. Positive financial incentives have a relatively small impact on GP choice, while the impact of qualitative incentives is relatively large. Status quo bias has a large impact on provider choice, which is more prominent in the case of GPs than in the case of pharmacies. CONCLUSION: The large impact of the status quo bias makes channeling consumers away from their current providers a daunting task, particularly in the case of GPs. PMID- 21029093 TI - Performing well on nursing home report cards: does it pay off? AB - OBJECTIVE: To examine whether high performance or improvement on quality measures leads to economic rewards for nursing homes in the presence of public reporting. DATA SOURCES: Data from 6,286 freestanding Medicare-certified nursing homes between 1999 and 2005 were identified in Medicare Cost Reports, Minimum Data Set, and Online Survey and Certification Reporting System. STUDY DESIGN: Using a facility-level fixed-effects model, the effect of public reporting on financial performance was measured by comparing each of four financial outcomes (revenues, expenses, operating, and total profit margins) before (1999-2002) to after (2003 2005) public reporting was initiated. The effects were estimated separately by level of performance and improvement over time. PRINCIPAL FINDINGS: Facilities that improved on publicly reported performance had increased revenues and higher profit margins after public reporting, mainly through increased Medicare admissions. High-scoring facilities showed similar patterns, though differences were not statistically significant. CONCLUSIONS: Providers that improve their performance under public reporting may receive a return on their investment in quality improvement. This supports the business case for public reporting. PMID- 21029094 TI - NR2B-NMDA receptor mediated modulation of the tyrosine phosphatase STEP regulates glutamate induced neuronal cell death. AB - The present study examines the role of a neuron-specific tyrosine phosphatase (STEP, striatal-enriched tyrosine phosphatase) in excitotoxic cell death. Our findings demonstrate that p38 MAPK, a stress-activated kinase that is known to play a role in the etiology of excitotoxic cell death is a substrate of STEP. Glutamate-mediated NMDA receptor stimulation leads to rapid but transient activation of p38 MAPK, which is primarily dependent on NR2A-NMDA receptor activation. Conversely, activation of NR2B-NMDA receptors leads to dephosphorylation and subsequent activation of STEP, which in turn leads to inactivation of p38 MAPK. Thus, during transient NMDA receptor stimulation, increases in STEP activity appears to limit the duration of activation of p38 MAPK and improves neuronal survival. However, if NR2B-NMDA receptor stimulation is sustained, protective effects of STEP activation are lost, as these stimuli cause significant degradation of active STEP, leading to secondary activation of p38 MAPK. Consistent with this observation, a cell transducible TAT-STEP peptide that constitutively binds to p38 MAPK attenuated neuronal cell death caused by sustained NMDA receptor stimulation. The findings imply that the activation and levels of STEP are dependent on the duration and magnitude of NR2B-NMDA receptor stimulation and STEP serves as a modulator of NMDA receptor dependent neuronal injury, through its regulation of p38 MAPK. PMID- 21029095 TI - Evidence based medicine: an academic's viewpoint - not so different to that of the clinician. PMID- 21029096 TI - Methods and mortality results of a health survey of purebred dogs in the UK. AB - OBJECTIVES: To collect information on the cause of death and longevity of dogs owned by members of the numerically largest breed clubs of 169 UK Kennel Club recognised breeds. METHODS: A cross-sectional study was carried out. Approximately 58,363 questionnaires were sent out to breed club members in 2004 (nine clubs failed to report the exact number of questionnaires sent out). Owners reported age at death and cause(s) of death for all dogs that had died within the previous 10 years. RESULTS: A total of 13,741 questionnaires (24% response rate) containing information on 15,881 deaths were included in the analysis. Breed specific response rates ranged from 64.7 to 4.5%. The median age at death was 11 years and 3 months (minimum=2 months, maximum=23 years and 5 months) and it varied by breed. The most common causes of death were cancer (n=4282, 27%), "old age" (n=2830, 18%) and cardiac conditions (n=1770, 11%). CLINICAL SIGNIFICANCE: This survey shows breed differences in lifespan and causes of death, and the results support previous evidence that smaller breeds tend to have longer lifespan compared with larger breeds. Although many of the breeds in the study may not be representative of the general pedigree dog population in the UK, the results do contribute to the limited information currently available. PMID- 21029097 TI - Haemoplasma infection is not a common cause of canine immune-mediated haemolytic anaemia in the UK. AB - OBJECTIVE: The aim of this study was to investigate whether the two canine haemoplasma species, Mycoplasma haemocanis and "Candidatus Mycoplasma haematoparvum," are commonly associated with immune-mediated haemolytic anaemia (IMHA) in UK dogs. METHODS: Three groups of dogs were recruited to the study: anaemic dogs with primary IMHA (n=37); anaemic dogs not meeting the inclusion criteria for primary IMHA (n=77) and non-anaemic dogs (n=113). DNA was extracted from 100 MUl of blood and subjected to real-time quantitative polymerase chain reaction (qPCR) assays for both species of Mycoplasma. Each assay incorporated co amplification of canine glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as an endogenous internal control. RESULTS: Canine GAPDH was successfully amplified by qPCR from all 227 canine blood samples but none contained M. haemocanis or "Candidatus M. haematoparvum" DNA. CLINICAL SIGNIFICANCE: Haemoplasma infection is uncommon in dogs in the UK and no evidence was found that these organisms act as triggers for IMHA. PMID- 21029098 TI - Population characteristics and survival in 127 referred cats with hypertrophic cardiomyopathy (1997 to 2005). AB - OBJECTIVES: To evaluate the characteristics and survival of a recent population of cats with hypertrophic cardiomyopathy. METHODS: Records at the Royal Veterinary College Queen Mother Hospital for Animals were searched for cats diagnosed with hypertrophic cardiomyopathy between 1997 and 2005. Referring veterinarians and owners were contacted to determine survival times. RESULTS: Cats with hypertrophic cardiomyopathy were evaluated for population characteristics (n=127) and survival times (n=109). Overall median survival from date of hypertrophic cardiomyopathy diagnosis at the Queen Mother Hospital for Animals was 1276 days. Cats with hypertrophic cardiomyopathy were younger (P=0.009), and more likely to be male (P<0.001) compared to a hospital control group (n=1473), and Ragdolls were over-represented (P<0.05). Characteristics associated with increased survival in univariate analysis included younger age (P=0.007), asymptomatic status (P<0.001), normal left atrial size (P<0.001) and presence of systolic anterior motion of the mitral valve (P=0.003). Systolic anterior motion was associated with asymptomatic status, and did not influence survival in asymptomatic cats or those in congestive heart failure. Age, left atrial size and breed were significantly associated with survival time in a multivariate analysis. CLINICAL SIGNIFICANCE: Cats with hypertrophic cardiomyopathy and left atrial enlargement have a poorer prognosis. The positive influence of systolic anterior motion on survival is likely to be linked to its association with asymptomatic status. PMID- 21029099 TI - Non-skeletal multicentric chondrosarcoma in the hindlimb of a dog. AB - An eight-year-old, spayed, female golden retriever was presented with progressive right hindlimb lameness and polyuria/polydipsia. Multiple soft tissue masses were palpable within the hindlimb muscles. A tentative diagnosis of sarcoma was made on fine needle aspiration. A computed tomography scan of the hindlimb and thorax confirmed the presence and location of the masses, none of which were associated with the bones of the hindlimb. In addition, two pulmonary lesions were identified in the right cranial lung lobe. A diagnosis of chondrosarcoma was confirmed on histopathology with a final diagnosis of extraskeletal chondrosarcoma. A high, hindlimb amputation was performed, and chemotherapy was initiated. Polyuria and polydipsia resolved 2 weeks postoperatively. Numerous lung lesions, suspected to be metastases were found on routine followup radiographs, 73 days post surgery after which the dog was lost to follow-up. PMID- 21029100 TI - Tongue entrapment by chew toys in two dogs. AB - Compression of a chew toy during regular play activity can create a vacuum effect eventually causing entrapment of oral tissues. Two cases of tongue entrapment are described, which resulted in severe tissue swelling, oedema and vascular obstruction. In the first dog, the toy was removed by the veterinary surgeon under general anaesthesia. Damage to the tongue proved to be reversible and the dog recovered uneventfully. In the second patient, the toy was forcefully removed by the owner. The resulting tongue necrosis required partial amputation. Treatment of this emergency condition consists of elimination of the negative pressure inside the toy by piercing it or even by insufflation of positive pressure inside the toy, and of an atraumatic manipulation to prevent further damage to the compromised tissues. PMID- 21029101 TI - Long term survival in two German shepherd dogs with Aspergillus-associated cavitary pulmonary lesions. PMID- 21029102 TI - Successful treatment of a retrobulbar mast cell tumour in a dog. PMID- 21029103 TI - Phylloplane location of glucosinolates in Barbarea spp. (Brassicaceae) and misleading assessment of host suitability by a specialist herbivore. AB - Glucosinolates are plant secondary metabolites used in host plant recognition by insects specialized on Brassicaceae, such as the diamondback moth (DBM), Plutella xylostella. Their perception as oviposition cues by females would seem to require their occurrence on the leaf surface, yet previous studies have reached opposite conclusions about whether glucosinolates are actually present on the surface of crucifer leaves. DBM oviposits extensively on Barbarea vulgaris, despite its larvae not being able to survive on this plant because of its content of feeding deterrent saponins. Glucosinolates and saponins in plant tissue and mechanically removed surface waxes from leaves of Barbarea spp. were analyzed with high performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC-MS). Surface waxes from leaves of Barbarea spp. contained glucosinolates, but not feeding-deterrent saponins. Our research is the first to show that glucosinolates are present on the leaf surface of Barbarea spp., but not in other crucifers investigated, resolving some conflicting results from previous studies. Our research is also the first to quantify glucosinolates on the leaf surface of a crucifer, and to show that the concentrations of glucosinolates found on the leaf surface of Barbarea spp. are sufficient to be perceived by ovipositing DBM. PMID- 21029104 TI - Improved nitrogen nutrition enhances root uptake, root-to-shoot translocation and remobilization of zinc ((65) Zn) in wheat. AB - This study focussed on the effect of increasing nitrogen (N) supply on root uptake and root-to-shoot translocation of zinc (Zn) as well as retranslocation of foliar-applied Zn in durum wheat (Triticum durum). Nutrient solution experiments were conducted to examine the root uptake and root-to-shoot translocation of (65) Zn in seedlings precultured with different N supplies. In additional experiments, the effect of varied N nutrition on retranslocation of foliar-applied (65) Zn was tested at both the vegetative and generative stages. When N supply was increased, the (65) Zn uptake by roots was enhanced by up to threefold and the (65) Zn translocation from roots to shoots increased by up to eightfold, while plant growth was affected to a much smaller degree. Retranslocation of (65) Zn from old into young leaves and from flag leaves to grains also showed marked positive responses to increasing N supply. The results demonstrate that the N-nutritional status of wheat affects major steps in the route of Zn from the growth medium to the grain, including its uptake, xylem transport and remobilization via phloem. Thus, N is a critical player in the uptake and accumulation of Zn in plants, which deserves special attention in biofortification of food crops with Zn. PMID- 21029105 TI - Photoprotection of reaction centers: thermal dissipation of absorbed light energy vs charge separation in lichens. AB - During desiccation, fluorescence emission and stable light-dependent charge separation in the reaction centers (RCs) of photosystem II (PSII) declined strongly in three different lichens: in Parmelia sulcata with an alga as the photobiont, in Peltigera neckeri with a cyanobacterium and in the tripartite lichen Lobaria pulmonaria. Most of the decline of fluorescence was caused by a decrease in the quantum efficiency of fluorescence emission. It indicated the activation of photoprotective thermal energy dissipation. Photochemical activity of the RCs was retained even after complete desiccation. It led to light dependent absorption changes and found expression in reversible increases in fluorescence or in fluorescence quenching. Lowering the temperature changed the direction of fluorescence responses in P. sulcata. The observations are interpreted to show that reversible light-induced increases in fluorescence emission in desiccated lichens indicate the functionality of the RCs of PSII. Photoprotection is achieved by the drainage of light energy to dissipating centers outside the RCs before stable charge separation can take place. Reversible quenching of fluorescence by strong illumination is suggested to indicate the conversion of the RCs from energy conserving to energy dissipating units. This permits them to avoid photoinactivation. On hydration, re-conversion occurs to energy-conserving RCs. PMID- 21029106 TI - Identification of proteins associated with water-deficit tolerance in C4 perennial grass species, Cynodon dactylon*Cynodon transvaalensis and Cynodon dactylon. AB - The study was conducted to examine differential proteomic responses to water deficit stress in hybrid bermudagrass [Cynodon dactylon (L.) Pers. *Cynodon transvaalensis Burtt Davy, cv. Tifway] and common bermudagrass (C. dactylon, cv. C299). Plants were exposed to water-deficit stress for 15 days by withholding irrigation in a growth chamber. Leaf electrolyte leakage increased and photochemical efficiency and relative water content declined under water-deficit stress, but the extent of changes in each of the physiological parameters for 'Tifway' was less pronounced than those for 'C299'. Total proteins of leaves were extracted from well-watered and water-deficit plants and separated by two dimensional gel electrophoresis. Of the 750 protein spots reproducibly detected, 32 proteins had increases in the abundance and 22 proteins exhibited decreases in the abundance in at least one genotype under water-deficit stress. A significantly higher number of proteins were found to accumulate in 'Tifway' than in 'C299' and 16 proteins with increasing abundance were detected only in 'Tifway' under water-deficit stress. All stress-responsive proteins were subjected to mass spectrometry analysis, which were mainly involved in metabolism, energy, cell growth/division, protein synthesis and stress defense. Functional analysis of differential drought-responsive proteins between the two genotypes suggests that the superior water-deficit tolerance in 'Tifway' bermudagrass could be mainly associated with less severe decline in the abundance level of proteins involved in photosynthesis (chlorophyll a-b, ATP synthase subunit alpha, phosphoribulokinase and ribulose-1,5-bisphosphate carboxylase/oxygenase) and greater increase in the abundance level of antioxidant defense proteins (superoxide dismutase, ascorbate peroxidase, dehydroascorbate reductase and peroxiredoxin), demonstrating that maintaining photosynthesis and active antioxidant defense mechanisms may play a critical role in C(4) grass adaptation to water-deficit stress. PMID- 21029107 TI - Cotton BCP genes encoding putative blue copper-binding proteins are functionally expressed in fiber development and involved in response to high-salinity and heavy metal stresses. AB - Copper is vitally required for plants at low concentrations but extremely toxic for plants at elevated concentrations. Plants have evolved a series of mechanisms to prevent the consequences of the excess or deficit of copper. These mechanisms require copper-interacting proteins involved in copper trafficking. Blue copper binding proteins (BCPs) are a class of copper proteins containing one blue copper binding domain binding a single type I copper. To investigate the role of BCPs in plant development and in response to stresses, we isolated nine cDNAs encoding the putative blue copper-binding proteins (GhBCPs) from cotton (Gossypium hirsutum). Meanwhile, four corresponding genes (including GhBCP1-GhBCP4), which contain a single intron inserted in their conserved position, were isolated from cotton genome. Quantitative reverse transcriptase-polymerase chain reaction (RT PCR) analysis indicated that the nine GhBCP genes are differentially expressed in cotton tissues. Among them, GhBCP1 and GhBCP4 were predominantly expressed in fibers, while the transcripts of GhBCP2 and GhBCP3 were accumulated at relatively high levels in fibers. These four genes were strongly expressed in early fiber elongation, but dramatically declined with further fiber development. In addition, these GhBCP genes were upregulated in fibers by Cu(2+) , Zn(2+) , high salinity and drought stresses, but downregulated in fibers by Al(3+) treatment. Overexpression of GhBCP1 and GhBCP4 in yeast (Schizosaccharomyces pombe) significantly increased the cell growth rate under Cu(2+) , Zn(2+) and high salinity stresses. These results suggested that these GhBCPs may participate in the regulation of fiber development and in response to high-salinity and heavy metal stresses in cotton. PMID- 21029108 TI - Somatosensory amplification as a possible source of subjective symptoms behind modern health worries. AB - The theoretically hypothesized connection between modern health worries (MHWs) and somatosensory amplification (SSA), as well as the factor structure of the Hungarian version of the MHW scale were investigated in a cross-sectional questionnaire study. A total of 163 university students (mean age = 21.3+/- 2.70 yrs; 44.2% male) and 145 patients (mean age = 49.4+/-17.51 yrs; 31.7% male) visiting their general practitioners (GPs) completed questionnaires assessing MHWs, SSA, subjective somatic symptoms (PHQ-15), and trait anxiety (STAI-T). The previously described four-factor structure of the MHW scale was confirmed using confirmatory factor analysis (CFA). In the linear regression analysis, participants' age and SSA scores were positively related to MHWs even after controlling for gender, anxiety, and subjective somatic symptom scores. The conclusions are that: MHWs are indicators of cognitive, behavioral and social level of sensitization for health-related concerns; SSA can provide the somatic background process for generation and/or misattribution of subjective somatic symptoms; better understanding of the cognitive-emotional background of MHWs could help to determine possible interventions. PMID- 21029109 TI - Transfusion practice in hip arthroplasty--a nationwide study. AB - BACKGROUND AND OBJECTIVES: The optimal transfusion strategy in hip arthroplasty remains controversial despite existing guidelines. The aim of this study was to evaluate the transfusion practice in patients undergoing primary total hip arthroplasty (THA) or revision total hip arthroplasty (RTHA) in Denmark. MATERIALS AND METHODS: We performed a retrospective cohort study of all patients undergoing THA or RTHA in Denmark in 2008. Primary outcomes were intercentre variation in red blood cell (RBC) transfusion rates and the timing of transfusion related to surgery. RESULTS: Six thousand nine hundred thirty-two THA patients and 1132 RTHA patients were included for analysis of which 1674 (24%) THA and 689 (61%) RTHA patients received RBC transfusion. Of these, 47% of THA and 73% of RTHA patients received transfusion on the day of surgery. Transfusion rates between centres varied from 7 to 71% and between 26 and 85% in THA and RTHA patients, respectively. Patients receiving RBC transfusion had longer length of stay and for THA patients an increased odds-ratio (5.5) of death within 90 days. CONCLUSION: Despite established guidelines, RBC transfusion practice in hip arthroplasty remains highly variable between Danish hospitals. The effect of RBC transfusion on outcome after hip arthroplasty should be established in prospective randomized controlled trials. PMID- 21029110 TI - Monitoring bacterial contamination of blood components in Germany: effect of contamination reduction measures. AB - BACKGROUND AND OBJECTIVES: National guidelines for monitoring bacterial contamination of blood components were introduced in Germany in 1997. Between 1998 and 2002, numerous measures were implemented to prevent bacterial contamination. This study investigates their impact on contamination rates. MATERIALS AND METHODS: Culture-based testing for bacterial detection on a random sample of blood components is part of routine quality control in German blood establishments. Using standardized questionnaires, data from the production periods 1998, 2001 and 2005/2006 were collected and analysed. RESULTS: The bacterial contamination rate of RBCs was reduced from 0.157% in 1998 to 0.029% in 2005/2006 (P<0.001). While the contamination rate of apheresis PCs remained nearly unchanged over the years, it dramatically decreased for pooled PCs by 70% to a contamination rate of 0.158% (P=0.001) within the last observation period, similar to that of apheresis PCs. The contamination rate of plasma decreased from 0.100% in 1998 to 0.019% in 2005/2006 (P=0.002). CONCLUSIONS: Precautionary measures significantly reduced bacterial contamination rates of blood components. Long-term monitoring with standardized methods is appropriate to evaluate the cumulative effect of contamination-preventing measures. PMID- 21029111 TI - Non-D Rh antibodies appearing after apheresis platelet transfusion: stimulation by red cells or microparticles? AB - BACKGROUND: Apheresis platelets (APs) have gained favour over whole blood-derived platelets on the presumption that they are less likely to provoke alloimmunization to red-blood-cell antigens. CASE REPORTS: Non-D Rh antibodies appeared in three patients after apheresis platelet transfusion. Anti-C and anti E arose in two female patients with previous antigen exposure. Both anti-c and anti-E arose in a male recipient with no prior transfusion history. MATERIALS AND METHODS: Fifty APs were analysed for residual RBCs and RBC-derived microparticles, using samples obtained from a local blood centre. Cells and microparticles were quantified with a flow cytometry gating scheme, using PE labelled anti-CD235a (glycophorin A) and FITC-labelled anti-CD41a (platelet gp IIb/IIIa) to distinguish lineage. RESULTS: Apheresis platelets were found to contain a mean of 7.5*10(6) (95% C.I. [6.3-8.5*10(6) ]) RBCs on one manufacturer's device and 5.2*10(6) (95% C.I. [4.0-6.3*10(6) ]) RBCs on another's. RBC-derived microparticles averaged 210.7*10(6) (95% C.I. [166.2 254.2*10(6) ]) on one manufacturer's device and 232.3*10(6) (95% C.I. [194.3 272.9*10(6) ]) on another's. These counts all correspond to volumes of <1 MUl. CONCLUSION: Despite RBC contamination of APs below commonly accepted thresholds for Rh immunogenicity, AP transfusion can provoke non-D Rh antibody formation. RBC-derived microparticles, smaller but more numerous than RBCs, are volumetrically comparable and may be a hitherto underappreciated antibody stimulus. Further microparticle research will guide considerations of extended phenotypic matching of platelet components. PMID- 21029112 TI - Miltenberger blood group antigen subtype III (Mi.III) supports Wr(b) expression. AB - BACKGROUND AND OBJECTIVES: Miltenberger blood group antigens belong to the complex MNS system. Miltenberger antigen subtype III (Mi.III) was previously found to promote the expression of band 3. Here, we investigated whether the direct interaction between band 3 and Mi.III-specific Gp.Mur (a glycophorin B-A-B hybrid) might affect the expression of related blood group antigens such as the Wright b (Wr(b) ) antigen. MATERIALS AND METHODS: (1) Band 3 genes of Mi.III+ and non-Mi.III (control) donors were sequenced to determine the genotypes of the Wright antigens. (2) The expression levels of Wr(b) , glycophorin A (GPA) and band 3 in Mi.III and the control erythrocytes were quantitatively assessed by flow cytometry. RESULTS: Mi.III erythrocytes expressed 22.5+/-6.6% more Wr(b) antigen than the control cells. The increase in Wr(b) in Mi.III cells was independent of their GPA levels. CONCLUSION: The elevated Wr(b) levels in Mi.III RBCs were likely linked to their higher band 3 levels. Higher band 3 densities on the Mi.III+ cell surface conceivably could drive complex formation between band 3 and GPA/Gp.Mur, thereby increasing the expression of Wr(b) . PMID- 21029113 TI - Infant eczema, infant sleeping problems, and mental health at 10 years of age: the prospective birth cohort study LISAplus. AB - BACKGROUND: Cross-sectional studies suggest an association between eczema and mental health problems, possibly modified by sleeping problems, but prospective evidence is missing. We aimed to prospectively investigate the relationship between infant eczema (within first 2 years of age), infant sleeping problems (within first 2 years of age), and the risk of mental health problems at 10 years of age. METHODS: Between 1997 and 1999, a population-based birth cohort was recruited in Munich, Leipzig, Wesel, and Bad Honnef, Germany, and followed until 10 years of age. Physician-diagnosed eczema, parent-reported sleeping problems, and known environmental risk factors for atopy were regularly assessed until 10 years of age. Mental health was measured using the Strengths and Difficulties Questionnaire (parent version) at 10 years of age. We applied logistic regression modeling adjusting for environmental and lifestyle factors, allergic comorbidity, and family history of eczema. RESULTS: From the original cohort of 3097 neonates, 1658 (54%) were followed until age 10, while 1578 (51%) were eligible for analysis. In the fully adjusted model, children with infant eczema were at increased risk of hyperactivity/inattention at 10 years of age [odds ratio (OR) 1.78; 95% confidence interval (95% CI) 1.02-3.09]. Infant eczema with concurrent sleeping problems predicted emotional problems [OR 2.63; 95% confidence interval (95% CI) 1.20-5.76] and conduct problems (OR 3.03; 95% CI 1.01-9.12) at 10 years of age. CONCLUSIONS: Infant eczema with concurrent sleeping problems appears to be a risk factor for the development of mental health problems. PMID- 21029114 TI - Polymorphisms, haplotypes and mutations in the protamine 1 and 2 genes. AB - Protamines are the most abundant nuclear proteins and alterations in their expression have been described in infertile patients. Also, protamine haplo insufficient mice have been described as infertile. Therefore, the protamine 1 and 2 genes have been considered important candidates in different mutational studies. In this article, we review all published articles related to protamine gene mutations and report new data on mutations from patients and controls drawn from the Spanish and Swedish populations. Sequencing of the protamine 1 and 2 genes in a total of 209 infertile patients and 152 fertility-proven controls from the Spanish and Swedish populations identified two novel and rare non-pathogenic missense mutations (R17C and R38M) in the protamine 1 gene and several additional polymorphisms. Furthermore, we have identified and we report for the first time five novel rare haplotypes encompassing the protamine 1 and 2 genes. A review of all available protamine gene mutational studies indicates that none of the reported missense mutations can be considered of proven pathogenicity. However, it is interesting to note that rare protamine 1 promoter variants have been reported only in infertile patients, but not in fertile control groups. Pathogenic high penetrance protamine gene missense mutations, if any, must be extremely rare. However, the detected presence of rare variants and haplotypes in infertile patients deserves further investigation. PMID- 21029115 TI - Prostasomes: inhibitors of capacitation and modulators of cellular signalling in human sperm. AB - Seminal fluid inhibits sperm capacitation mainly because of its high cholesterol content. Prostasomes are the main source of cholesterol in seminal fluid. They are known to have numerous protective properties and are able to transfer proteins and lipids to spermatozoa, but their impact on capacitation and acrosome reaction (AR) is not yet well understood. The aim of this study was to determine the effects of prostasomes on human sperm capacitation and AR. After 80% Percoll selection, freshly ejaculated human spermatozoa were incubated for 3 h under capacitating conditions with prostasomes, phosphodiesterase inhibitor 3-iso-butyl methylxantine (IBMX), or a combination of prostasomes and IBMX. Physiological concentration of prostasomes significantly decreased tyrosine phosphorylation levels of human sperm capacitation markers P110 and P80 (p < 0.01), and the proportions of capacitated (p < 0.05) and acrosome-reacted spermatozoa (p < 0.05). Prostasomes significantly increased the proportion of spermatozoa that did not incorporate propidium iodide and significantly attenuated the effect of IBMX on P110 tyrosine phosphorylation. Prostasomes had no effect on the pH(i) increase associated with capacitation. They significantly increased intracellular cAMP concentration ([cAMP](i)) and, when prostasomes and IBMX were present together, [cAMP](i) was further increased. To our knowledge, this is the first study to show clearly that prostasomes inhibit capacitation and spontaneous AR. PMID- 21029116 TI - When it is too hot for photosynthesis: heat-induced instability of photosynthesis in relation to respiratory burst, cell permeability changes and H2O2 formation. AB - Photosynthesis rate (A(n)) becomes unstable above a threshold temperature, and the recovery upon return to low temperature varies because of reasons not fully understood. We investigated responses of A(n), dark respiration and chlorophyll fluorescence to supraoptimal temperatures of varying duration and kinetics in Phaseolus vulgaris asking whether the instability of photosynthesis under severe heat stress is associated with cellular damage. Cellular damage was assessed by Evans blue penetration (enhanced membrane permeability) and by H2O2 generation [3,3'-diaminobenzidine 4HCl (DAB)-staining]. Critical temperature for dark fluorescence (F(0) ) rise (T(F)) was at 46-48 degrees C, and a burst of respiration was observed near T(F). However, A(n) was strongly inhibited already before T(F) was reached. Membrane permeability increased with temperature according to a switch-type response, with enhanced permeability observed above 48 degrees C. Experiments with varying heat pulse lengths and intensities underscored the threshold-type loss of photosynthetic function, and indicated that the degree of photosynthetic deterioration and cellular damage depended on accumulated heat-dose. Beyond the 'point of no return', propagation of cellular damage and reduction of photosynthesis continued upon transfer to lower temperatures and photosynthetic recovery was slow or absent. We conclude that instability of photosynthesis under severe heat stress is associated with time dependent propagation of cellular lesions. PMID- 21029117 TI - Dynamic changes of canopy-scale mesophyll conductance to CO2 diffusion of sunflower as affected by CO2 concentration and abscisic acid. AB - Leaf-level measurements have shown that mesophyll conductance (g(m)) can vary rapidly in response to CO2 and other environmental factors, but similar studies at the canopy-scale are missing. Here, we report the effect of short-term variation of CO2 concentration on canopy-scale g(m) and other CO2 exchange parameters of sunflower (Helianthus annuus L.) stands in the presence and absence of abscisic acid (ABA) in their nutrient solution. g(m) was estimated from gas exchange and on-line carbon isotope discrimination (Delta(obs)) in a 13CO2/12CO2) gas exchange mesocosm. The isotopic contribution of (photo)respiration to stand scale Delta(obs) was determined with the experimental approach of Tcherkez et al. Without ABA, short-term exposures to different CO2 concentrations (C(a) 100 to 900 umol mol-1) had little effect on canopy-scale g(m) . But, addition of ABA strongly altered the CO2-response: g(m) was high (approx. 0.5 mol CO2 m-2 s-1) at C(a) <200 umol mol-1 and decreased to <0.1 mol CO2 m-2 s-1 at C(a) >400 umol mol 1. In the absence of ABA, the contribution of (photo)respiration to stand-scale Delta(obs) was high at low C(a) (7.2 0/00) and decreased to <2 0/00 at C(a) > 400 umol mol-1. Treatment with ABA halved this effect at all C(a) . PMID- 21029118 TI - From body-talk to body-stories: body work in complementary and alternative medicine. AB - This paper explores the 'body work' undertaken by practitioners of complementary and alternative medicine (CAM), in the light of ethnographic research on the education of osteopaths and homeopaths. The data presented focus on practitioners' experiences of learning to communicate, touch and facilitate the healing process for their patients. Two new concepts are introduced: listening to body-talk and constructing body-stories, which are discussed as aspects of body work. Body-talk expresses the idea that the embodied patient is not a passive recipient of healthcare, but that the 'body' is able to communicate its distress and its needs. The body-story concept highlights the interactional nature of the therapeutic encounter and the profound interrelation between the treatment and case-taking aspects of the practitioner's clinical tasks. By drawing on key sociological concepts of the body and embodiment, reflexivity and narrative, I argue that the dialogical construction of body-stories challenges Cartesian dualism. Finally, I discuss what the data might mean for the future development of the sociological concept of 'body work', drawing particular attention to the necessity to problematise the concept of the 'body' and to pay great attention to body work as embodied work. PMID- 21029121 TI - Effect of pacing-induced ventricular dyssynchrony on right ventricular function. AB - BACKGROUND: Asynchronous electrical activation induced by right ventricular (RV) pacing can cause several abnormalities in left ventricular (LV) function. However, the effect of ventricular pacing on RV function has not been well established. We evaluated RV function in patients undergoing long-term RV pacing. METHODS: Eighty-five patients and 24 healthy controls were included. After pacemaker implantation, conventional echocardiography and strain imaging were used to analyze RV function. Strain imaging measurements included peak systolic strain and strain rate. LV function and ventricular dyssynchrony by tissue Doppler imaging (TDI) were assessed. Intra- and interobserver variabilities of TDI parameters were tested on 15 randomly selected cases. RESULTS: All patients were in New York Heart Association functional class I or II and percentage of ventricular pacing was 96 +/- 4%. RV apical induced interventricular dyssynchrony in 49 patients (60%). LV dyssynchrony was found in 51 patients (60%), when the parameter examined was the standard deviation of the time to peak myocardial systolic velocity of all 12 segments greater than 34 ms. Likewise, septal-to lateral delay >= 65 ms was found in 31 patients (36%). All echocardiographic indexes of RV function were similar between patients and controls (strain: -22.8 +/- 5.8% vs -22.1 +/- 5.6%, P = 0.630; strain rate: -1.47 +/- 0.91 s(-1) vs -1.42 +/- 0.39 s(-1) , P = 0.702). Intra- and interobserver variability for RV strain was 3.1% and 5.3%, and strain rate was 1.3% and 2.1%, respectively. CONCLUSIONS: In patients with standard pacing indications, RV apical pacing did not seem to affect RV systolic function, despite induction of electromechanical dyssynchrony. PMID- 21029120 TI - Long-term RV threshold behavior by automated measurements: safety is the standpoint of pacemaker longevity! AB - BACKGROUND: We studied long-term right ventricular (RV) pacing threshold (RVPT) behavior in patients consecutively implanted with pacemakers capable of automatic output reprogramming tracked by automatic RV threshold measurement (automatic verification of capture [AVC]). METHODS: All the patients had state-of-the art steroid-eluting bipolar pacing leads and were RV-paced by an AVC algorithm from the three American manufacturers. Follow-up occurred twice in the first year after implantation, then yearly until approaching elective replacement indicator. RESULTS: Three hundred and twenty-one patients aged 73 +/- 12 years were observed for 49 +/- 26 months on average. At implantation, RVPT was 0.54 +/- 0.2 V at 0.4 ms at an average 774 +/- 217 Omega impedance. Forty-one of the 321 patients (12.8%) had a permanent RVPT increase above 1.5 V at 0.4 ms: RVPT was between 1.6 and 2.5 V in 29 of 321 (9%) patients, whereas it was between 2.6 and 3.5 V in seven of 321 (2.2%) patients, and >3.5 V in five of 321 (1.5%) patients. No exit block occurred because of automatic RV output adjustment by AVC algorithms. No predictor of RVPT increase was found at multivariable analysis. The maximum RVPT increase occurred within 12 months from implantation in 19 of 321 (5.9%) patients, between the first and the second year in 12 of 321 (3.7%), between the second and the sixth year in eight of 321 (2.5%), and after the sixth year in two of 321 (0.6%). CONCLUSION: Despite technologic improvement in lead manufacturing, long-term increase of the RVPT occurs in about 13% of patients, possibly representing a serious safety issue in 3.7% when 2.5 V at 0.4 ms is exceeded. AVC algorithms can improve patients' safety by automatic tailoring of the pacing output to threshold fluctuations, while maximizing device longevity. PMID- 21029119 TI - Analysis of side population cells derived from dental pulp tissue. AB - AIM: To investigate the characteristics of side population (SP) cells derived from the dental pulp of young and aged rats. METHODOLOGY: Maxillary and mandibular incisors were extracted from 5-week-old (young) rats and 60- to 80 week-old (aged) rats. Coronal pulp tissue was removed mechanically, and single cell suspensions were prepared using collagenase and dispase. Cells were stained with Hoechst 33342 and sorted with an fluorescence-activated cell sorter (FACS). Isolated SP and main population (MP) cells were analysed by real-time reverse transcription polymerase chain reaction, immunohistochemical localization and cell cycle determination. Two-way analysis of variance and the multiple comparison Scheffe test were used for statistical analysis (P<0.05). RESULTS: Approximately 0.40% of pulp cells in young rats and 0.11% in aged rats comprised SP cells. SP cells expressed a higher mRNA level of ATP-binding cassette transporter G2 (ABCG2), but lower mRNA levels of nestin, alkaline phosphatase, p16 and p57 than MP cells in both age groups. Immunohistochemical observation revealed ABCG2-positive cells localized in the cell-rich zone and nestin in the odontoblastic layer in both groups. Furthermore, the majority of both young and aged SP and MP cells were in growth arrest of the G(0) /G(1) phase. CONCLUSION: The FACS analysis revealed a decrease in the proportion of SP cells with age, whilst p16 mRNA expression indicated an increase in cell senescence. The cell cycles of SP and MP cells from both young and aged dental pulp were generally in the G0/G1 phase. PMID- 21029122 TI - Pocket salvage in patients with infected device pocket and limited vascular access: a viable last resort? AB - This case study describes a pocket salvage procedure in a patient with a device pocket infection and limited vascular access. This case report also provides a literature review of recent studies addressing the success of pocket salvage procedures in patients not showing any signs of systemic infection. PMID- 21029123 TI - The final option and a desperate measure!! PMID- 21029124 TI - Impedance changes on defibrillation coils after atrial fibrillation ablation: lead damage or electromechanical interference? AB - Fluctuation of impedance on defibrillator leads is highly suggestive of lead failure. A drop in impedance is associated with insulation defects while high impedance is suggestive of lead fracture. In this case report, we described a patient where electromagnetic interference from radiofrequency ablation near the site of superior vena cava coil caused the sensed impedance to fluctuate without uneventful outcomes and we discussed the possible mechanism. Both electromagnetic interference and defibrillator lead insulation defect can result in low threshold and inappropriate shocks. Sometimes electromagnetic interference may result in physical damage of the implanted system and may result in subsequent fluctuations in impedance. Awareness of electromagnetic interference that can cause fluctuating impedance without structural damage can help in making appropriate diagnosis and may avoid unnecessary procedures. PMID- 21029125 TI - Anatomical perspective on radiofrequency ablation of AV nodal reentry tachycardia after Mustard correction for transposition of the great arteries. AB - A case of radiofrequency catheter ablation of atrioventricular (AV) nodal reentry tachycardia, in a patient with transposition of the great arteries after venous rerouting according to Mustard, is described. An electroanatomical map of the His and AV nodal region was created from inside the systemic venous atrium. Retrograde mapping of the pulmonary venous atrium was performed and the arterial catheter retracted to a position in close proximity to the venous catheter inside the intraatrial baffle. This position was chosen to deliver radiofrequency current. PMID- 21029126 TI - Depression and heart disease: uncracked mystery of the chicken and the egg. PMID- 21029127 TI - The prevalence and cost of the faint and fall problem in the state of Utah. AB - BACKGROUND: Understanding the frequency and economic impact of faint and fall is a prerequisite for the creation of cost-effective diagnostic approaches. METHODS: We evaluated the total number of patients presenting with faint or fall to the University of Utah Health Care System between November 1, 2008, and October 31, 2009. Using these data, we estimated the prevalence and total cost of the faint and fall problem in the state of Utah. RESULTS: A total of 1,936 and 6,043 patients presented with faint and fall resulting in a total number of visits equal to 2,701 and 8,163, respectively. The yearly prevalence of faints was 9.5 patients (13.2 visits) per 1,000 inhabitants and the yearly prevalence of falls was 29.8 patients (40.2 visits) per 1,000 inhabitants. The prevalence of faints and falls progressively increased with age, reaching the values of 40 and 115 per 1,000 inhabitants in subjects aged >80 years. In both patient populations, two thirds of visits were outpatient evaluations. While the cardiovascular service was involved in the outpatient evaluation of faint visits in 24% of the cases, <1% of outpatient fall visits resulted in a cardiovascular consultation. The average payments received per faint and fall patient evaluations were $2,517 and $3,200, respectively, resulting in an estimated yearly cost equal to $90,901,958 and $351,959,040, respectively. CONCLUSION: This study highlights the magnitude of the faint and fall problem in the state of Utah. Our results provide all stakeholders with a frame of reference for the creation of cost-effective diagnostic approaches. PMID- 21029128 TI - Early detection of adverse events with daily remote monitoring versus quarterly standard follow-up program in patients with CRT-D. AB - BACKGROUND: A relative high rate of clinical and device-related adverse events (AE) is generally reported in patients with implantable defibrillators for cardiac resynchronization therapy (CRT-D). Aim of this study was to compare a daily remote monitoring (RM) to a standard program of in-office visits. METHODS AND RESULTS: We retrospectively analyzed RM database and hospital files of 99 CRT D consecutive patients who were visited in the out-patient clinic every 3-4 months; thirty-three patients were in addition controlled remotely with RM (RM group). Kaplan-Meier curves of clinical or device-related AE-free rates were obtained. During a median follow-up of 7 months, clinical AEs were: ventricular and atrial arrhythmias in 14 and 11 patients, low CRT pacing in nine, heart failure, strokes, or death in 15. Device-related AEs were: insufficient pacing/sensing performances in nine patients, lead dislodgement in five. As comparing the RM group with the remaining patients, Kaplan-Meier curves of clinical AEs diverged to significantly different rates: 23.8% (confidence interval [CI] 0.1%-47.5%) in the RM group and 48.7% (21.6-75.7%) in the remaining patients (P = 0.00002), with a hazard ratio of 0.14 (CI 0.06-0.37). Nondivergent Kaplan-Meier curves were obtained for device-related AE-free rates. CONCLUSION: CRT-D patients followed with quarterly in-office visits without a daily RM system had an 86% higher risk of delayed detection of clinical AEs, during a median follow-up of 7 months. PMID- 21029129 TI - Maximizing efficiency of alternation algorithms for hemodynamic optimization of the AV delay of cardiac resynchronization therapy. AB - BACKGROUND: During optimization of the atrioventricular (AV) delay of cardiac resynchronization therapy (CRT), it is not known exactly which windows of time around the transition are most informative for identification of the optimum. METHOD AND RESULTS: IN 22 patients with CRT, we performed AV delay optimization using continuous noninvasive hemodynamics. We used signal-to-noise ratio to determine the most efficient averaging window location and width. We found that it is most efficient to position the averaging windows immediately before and immediately after the transition in AV delay. For example, skipping five beats after the transition decreases signal-to-noise ratio by 17.5% (P < 0.0001). Similarly, skipping five beats immediately before the transition reduces signal to-noise ratio by 11.7% (P < 0.0001). The best choice of "fixed" averaging window width was found to be six beats, with signal-to-noise ratio falling by, for example, 41% for a one-beat window (P = 0.0002). However, even better was to set the window width for each patient to match one respiratory cycle. We observed that the pre- and posttransition signal-to-noise ratio traces begin to diverge three beats after the transition in AV delay. We believe this represents the time taken for the peripheral response to pacing-induced changes in stroke volume to occur. CONCLUSIONS: THE most efficient way to use alternating transitions for the hemodynamic optimization of CRT is to use an averaging window of one respiratory cycle, and not to skip any beats between the pretransition and posttransition averaging windows. PMID- 21029130 TI - Identification of a conduction gap of the mitral isthmus by using a novel high density mapping catheter. AB - Peri-mitral atrial flutter, which is a type of macroreentrant atrial tachycardia circulating around the mitral annulus, was terminated with the guidance of the high-density mapping catheter. A 72-year-old woman with atrial fibrillation and atrial tachycardia presented with symptoms of congestive heart failure. The recurrent peri-mitral atrial flutter following the initial catheter ablation for atrial tachycardia and atrial fibrillation was terminated by radiofrequency application on the gap that was identified using a novel high-density mapping catheter. PMID- 21029131 TI - Flecainide-associated bradycardia-dependent torsade de pointes: another potential mechanism of proarrhythmia. AB - Although flecainide has a risk of proarrhythmia in patients with structural heart disease, its mechanism has been mainly ascribed to use-dependency and a rapid ventricular response to organized atrial tachyarrhythmias or to ventricular tachycardia. We present a patient who experienced recurrent syncope due to bradycardia-dependent torsade de pointes (TdP) associated with flecainide-related bradycardia and QT prolongation. Bradycardia-dependent TdP with QT prolongation can be considered as one of mechanisms of flecainide-induced proarrhythmia. PMID- 21029132 TI - Relationship between P-wave duration and atrial electromechanical delay assessed by tissue Doppler echocardiography. AB - BACKGROUND: The aim of the study was to assess the relationship between P-wave duration on the surface electrocardiogram (ECG) and echocardiographic parameters of atrial electromechanical delay (EMD), as well as contraction synchrony during different atrial pacing modalities. METHODS: In 57 patients with sinus node disease and prolonged sinus P-wave duration treated with multisite atrial pacing (MSAp), the EMD was measured by tissue Doppler in several left and right atrial sites during sinus rhythm, MSAp, and single-site pacing at right atrial appendage (RAAp), Bachmann's bundle (BBp) region, and coronary sinus (CSp) ostium. Regional atrial synchrony was calculated on the basis of EMD. RESULTS: P-wave duration was 141 +/- 16, 120 +/- 17, 138 +/- 17, 144 +/- 16, and 160 +/- 19 ms during sinus rhythm, MSAp, BBp, CSp, and RAAp, respectively (P < 0.001 RAAp and MSAp vs other). P-wave duration correlated with all atrial EMDs as well as interatrial and intraleft atrial parameters of dyssynchrony. In multivariate analysis, the EMD in lateral left atrial wall was the strongest predictor of P-wave duration (beta 0.41; P < 0.001). The relationship between P-wave duration and the atrial EMDs was most prominent during RAAp (all left atrial walls r > 0.51; P < 0.01) and BBp (all atrial walls r > 0.42; P < 0.05), while during sinus rhythm and CSp, only weak correlation between echo and ECG was found. Neither of the tissue Doppler parameters correlated with P-wave duration during MSAp. Interatrial dyssynchrony correlated with P-wave duration during sinus rhythm and RAAp and intraleft atrial dyssynchrony only during sinus rhythm. CONCLUSIONS: P-wave duration of the surface ECG is highly correlated with the atrial EMD, the relationship is specific for each pacing modality. PMID- 21029133 TI - Early diagnosis and rescue pericardiocentesis for acute cardiac tamponade during radiofrequency ablation for arrhythmias. Is fluoroscopy enough? AB - BACKGROUND: With the number of complex catheter ablation procedures increasing, procedure-related acute cardiac tamponade is encountered more frequently in the cardiac catheterization laboratory. Survival depends on prompt recognition and rescue pericardiocentesis. OBJECTIVE: The aim of this report was to validate fluoroscopic heart silhouette characteristics associated with cardiac tamponade as a diagnostic method, and evaluate the safety and effectiveness of fluoroscopy guided pericardiocentesis during catheter ablation. METHODS: All cases of acute cardiac tamponade that occurred in the cardiac catheterization laboratory during radiofrequency catheter ablation from March 2004 to November 2009 were reviewed retrospectively. RESULTS: Of 1,832 catheter ablation procedures performed during a 5-year period, 10 (0.55%) were complicated by cardiac tamponade. Fluoroscopic examination confirmed the diagnosis in all 10 patients and demonstrated effusions before hypotension in four patients. All patients were stabilized by fluoroscopy guided pericardiocentesis with placement of an indwelling catheter and autologous transfusion. The time interval between recognition of cardiac tamponade and completion of pericardiocentesis was 6.0 +/- 1.8 minutes (range 3-9 minutes). The mean aspirated blood volume was 437 mL (range 110-1,400 mL), and the mean autotransfused blood volume was 425 mL (range 100-1,384 mL). Surgical repair of the cardiac perforation was needed in one patient. No procedure-related death occurred. CONCLUSION: A reduction in the excursion of cardiac silhouette on fluoroscopy is an early diagnostic sign of cardiac tamponade during radiofrequency ablation. Fluoroscopy-guided pericardiocentesis is a safe and effective management strategy for cardiac tamponade developed in the cardiac catheterization laboratory. PMID- 21029134 TI - Upstream effect for atrial fibrillation: still a dilemma? AB - Atrial fibrillation is the most common arrhythmia in clinical practice. Ion channel blocking agents are often characterized by limited long-term efficacy and several side effects. In addition, ablative invasive procedures are neither easily accessible nor always efficacious. The "upstream therapy," which includes angiotensin-converting enzyme inhibitors, aldosterone receptor antagonists, statins, glucocorticoids, and omega-3 poly-unsaturated fatty acids, targets arrhythmia substrate, influencing atrial structural and electrical remodeling that play an essential role in atrial fibrillation induction and maintenance. The mechanisms involved and the most important clinical evidence regarding the upstream therapy influence on atrial fibrillation are presented in this review. Some open questions are also proposed. PMID- 21029135 TI - Advanced image fusion to overlay coronary sinus anatomy with real-time fluoroscopy to facilitate left ventricular lead implantation in CRT. AB - BACKGROUND: Failure rate for left ventricular (LV) lead implantation in cardiac resynchronization therapy (CRT) is up to 12%. The use of segmentation tools, advanced image registration software, and high-fidelity images from computerized tomography (CT) and cardiac magnetic resonance (CMR) of the coronary sinus (CS) can guide LV lead implantation. We evaluated the feasibility of advanced image registration onto live fluoroscopic images to allow successful LV lead placement. METHODS: Twelve patients (11 male, 59 +/- 16.8 years) undergoing CRT had three dimensional (3D) whole-heart imaging (six CT, six CMR). Eight patients had at least one previously failed LV lead implant. Using segmentation software, anatomical models of the cardiac chambers, CS, and its branches were overlaid onto the live fluoroscopy using a prototype version of the Philips EP Navigator software to guide lead implantation. RESULTS: We achieved high-fidelity segmentations of cardiac chambers, coronary vein anatomy, and accurate registration between the 3D anatomical models and the live fluoroscopy in all 12 patients confirmed by balloon occlusion angiography. The CS was cannulated successfully in every patient and in 11, an LV lead was implanted successfully. (One patient had no acceptable lead values due to extensive myocardial scar). CONCLUSION: Using overlaid 3D segmentations of the CS and cardiac chambers, it is feasible to guide CRT implantation in real time by fusing advanced imaging and fluoroscopy. This enabled successful CRT in a group of patients with previously failed implants. This technology has the potential to facilitate CRT and improve implant success. PMID- 21029136 TI - Long-term outcome of leads and patients following robotic epicardial left ventricular lead placement for cardiac resynchronization therapy. AB - INTRODUCTION: In cardiac resynchronization therapy (CRT), positive clinical response and reverse remodeling have been reported using robotically assisted left ventricular (LV) epicardial lead placement. However, the long-term performance of epicardial leads and long-term outcome of patients who undergo CRT via robotic assistance are unknown. In addition, since the LV lead placement is more invasive than a transvenous procedure, it is important to identify patients at higher risk of complications. METHODS: We evaluated 78 consecutive patients (70 +/- 11 years, 50 male) who underwent robotic epicardial LV lead placement. The short- (<12 months) and long-term (>= 12 months) lead performance was determined through device interrogations. Mortality data were determined by contact with the patient's family and referring physicians and confirmed using the Social Security Death Index. RESULTS: All patients had successful lead placement and were discharged in stable condition. When compared to the time of implantation, there was a significant increase in pacing threshold (1.0 +/- 0.5 vs 2.14 +/- 1.2; P < 0.001) and decrease in lead impedance (1010 +/- 240 Omega vs 491 +/- 209 Omega; P < 0.001) at short-term follow-up. The pacing threshold (2.3 +/- 1.2 vs 2.14 +/- 1.2; P = 0.30) and lead impedance (451 +/- 157 Omega vs 491 +/- 209 Omega; P = 0.10) remained stable during long-term follow-up when compared to short-term values. At a follow-up of 44 +/- 21 months, there were 20 deaths (26%). These patients were older (77 +/- 7 vs 67 +/- 11 years; P = 0.001) and had a lower ejection fraction (EF) (13 +/- 7% vs 18 +/- 9%; P = 0.02) than surviving patients. CONCLUSION: Robotically implanted epicardial LV leads for CRT perform well over short- and long-term follow-up. Older patients with a very low EF are at higher risk of death. The risks and benefits of this procedure should be carefully considered in these patients. PMID- 21029137 TI - Comparison of the point-by-point versus catheter dragging technique for curative radiofrequency ablation of atrial fibrillation. AB - BACKGROUND: The relationship between the applied techniques and clinical outcomes after radiofrequency (RF) ablation of atrial fibrillation (AF) remains unclear. We compared the results of ablation by RF delivered via a point-by-point versus catheter dragging technique for the treatment of AF. METHODS: This study included 66 patients with drug-refractory AF who underwent circumferential pulmonary vein (PV) ablation. A point-by-point technique was used in 35 (53%) patients (Group I), and catheter dragging technique in the remaining 31 (47%) patients (Group II). If AF persisted or remained inducible after the PV isolation, additional ablation of complex fractionated atrial electrograms and linear ablation were performed. RESULTS: Significantly, fewer RF applications were delivered in Group II than in Group I. The total RF energy duration delivered was comparable between the two groups (P = 0.55). However, the total energy of RF deliveries was significantly greater in Group II than in Group I (P = 0.02). Despite a longer fluoroscopic exposure time (P = 0.01), the total procedural duration was significantly shorter in Group II than in Group I (P = 0.005). Within 3 months after a single ablation procedure, 24 patients (69%) in Group I versus 13 patients (42%) in Group II had >=1 recurrence(s) of atrial tachyarrhythmias (P = 0.03). A multivariate analysis showed that a point-by-point ablation was the only independent predictor of early atrial tachyarrhythmia recurrences. CONCLUSIONS: The catheter dragging technique for ablation of AF was associated with a lower early recurrence rate of atrial tachyarrhythmias than the point-by-point technique. PMID- 21029138 TI - Incidence and antimicrobial resistance of enteropathogens isolated from an integrated aquaculture system. AB - AIMS: To evaluate an integrated aquaculture system, microbiological analyses of water used in this system were carried out and the incidence and antimicrobial resistance of enteropathogens were determined in the related ecosystem. METHODS AND RESULTS: Microbiological analysis was undertaken for Salmonella sp., Shigella sp., Vibrio sp. and Aeromonas sp. The disc-diffusion method was performed according to the Clinical and Laboratory Standards Institute. Water samples tested had 32.9% of faecal coliform rates (<=1600 per 100 ml) in accordance with WHO for pisciculture in wastewater. Salmonella spp. were detected in 14.5% of the samples. From a total of 33 strains, 15.1% were resistant to one or two antimicrobial drugs tested and multidrug resistance was not observed. Aeromonas spp. were identified in 91.6% of the samples. From a total of 416 strains, resistance to one antimicrobial class was observed in 66.3% and multidrug resistance in 37.7%. CONCLUSIONS: This system reflects the community profile, drawing attention to the circulation of pathogens, because the genes coding for resistance to classical antibiotics and broad spectrum are a public health problem. SIGNIFICANCE AND IMPACT OF THE STUDY: The reuse of water resources requires continuous monitoring as the system is subject to treatment failure, which can result in the spread of bacterial pathogens. PMID- 21029139 TI - The ability of nisin F to control Staphylococcus aureus infection in the peritoneal cavity, as studied in mice. AB - AIMS: To determine the ability of nisin F to control systematic infection caused by Staphylococcus aureus, using C57BL/6 mice as a model. METHODS AND RESULTS: Twelve mice were intraperitoneally injected with 1 * 10(8) viable cells of Staph. aureus Xen 36 containing the modified Photorhabdus luminescence luxABCDE operon on plasmid pAUL-A Tn4001. After 4 h, six mice were intraperitoneally injected with 640 arbitrary units (AU) nisin F, and six were injected with sterile saline. Six mice, not infected with Staph. aureus, were treated with nisin F, and six not infected were left untreated. The viability of Staph. aureus Xen 36 was monitored over 48 h by recording photon emission levels. Nisin F suppressed Staph. aureus for 15 min in vivo. No abnormalities were recorded in blood analyses and internal organs of mice treated with nisin F. CONCLUSIONS: Nisin F suppressed the growth of Staph. aureus in the peritoneal cavity for at least 15 min. Re-emergence of Staph. aureus bioluminescence over the next 44 h suggests that nisin F was inactivated, most probably by proteolytic enzymes. SIGNIFICANCE AND IMPACT OF THE STUDY: A single dosage of nisin F administered in the peritoneal cavity controlled the growth of Staph. aureus for at least 15 min in vivo. PMID- 21029140 TI - Detection of Botrytis cinerea by loop-mediated isothermal amplification. AB - AIMS: To develop a sensitive, rapid and simple method for detection of Botrytis cinerea based on loop-mediated isothermal amplification (LAMP) that would be suitable for use outside a conventional laboratory setting. METHODS AND RESULTS: A LAMP assay was designed based on the intergenic spacer of the B. cinerea nuclear ribosomal DNA (rDNA). The resulting assay was characterized in terms of sensitivity and specificity using DNA extracted from cultures. The assay consistently amplified 65 pg B. cinerea DNA. No cross-reactivity was observed with a range of other fungal pathogens, with the exception of the closely related species Botrytis pelargonii. Use of a novel real-time LAMP platform (the OptiGene Genie I) allowed detection of B. cinerea in infected rose petals, with amplification occurring in <15 min. CONCLUSIONS: The LAMP assay that was developed is suitable for rapid detection of B. cinerea in infected plant material. SIGNIFICANCE AND IMPACT OF THE STUDY: The LAMP method combines the sensitivity and specificity of nucleic acid-based methods with simplified equipment and a reduced reaction time. These features make the method potentially suitable for on-site use, where the results of testing could help to inform decisions regarding the storage and processing of commodities affected by B. cinerea, such as cut flowers, fruit and vegetables. PMID- 21029141 TI - Calling it a day on proceduralism in bioethics? PMID- 21029142 TI - Quantitative risk assessment modeling for nonhomogeneous urban road tunnels. AB - Urban road tunnels provide an increasingly cost-effective engineering solution, especially in compact cities like Singapore. For some urban road tunnels, tunnel characteristics such as tunnel configurations, geometries, provisions of tunnel electrical and mechanical systems, traffic volumes, etc. may vary from one section to another. These urban road tunnels that have characterized nonuniform parameters are referred to as nonhomogeneous urban road tunnels. In this study, a novel quantitative risk assessment (QRA) model is proposed for nonhomogeneous urban road tunnels because the existing QRA models for road tunnels are inapplicable to assess the risks in these road tunnels. This model uses a tunnel segmentation principle whereby a nonhomogeneous urban road tunnel is divided into various homogenous sections. Individual risk for road tunnel sections as well as the integrated risk indices for the entire road tunnel is defined. The article then proceeds to develop a new QRA model for each of the homogeneous sections. Compared to the existing QRA models for road tunnels, this section-based model incorporates one additional top event-toxic gases due to traffic congestion-and employs the Poisson regression method to estimate the vehicle accident frequencies of tunnel sections. This article further illustrates an aggregated QRA model for nonhomogeneous urban tunnels by integrating the section-based QRA models. Finally, a case study in Singapore is carried out. PMID- 21029143 TI - Meanings of participating in a lifestyle programme for persons with psychiatric disabilities. AB - Lifestyle changes that affect physical and psychological health are described in research literature; however, the meaning of participating in a lifestyle intervention programme together with the staff has not been described. This study illuminates meanings of participating in a lifestyle programme as experienced by persons with psychiatric disabilities. The first author interviewed five women and six men with schizophrenia and depressive syndrome, aged 26-53, participating in a lifestyle programme. The transcribed interviews were analysed using a phenomenological hermeneutic approach inspired by the philosophy of Ricoeur. Meanings of participating in a lifestyle programme include my health can be improved as both the physical effects and the obstacles are considered and the daily life is partially given a changed content in new experiences and by participating in something to take pride in. The meanings of participating together with the staff mean an increased sense of closeness and equality with the staff expressed in changes in relationships and the difference between the two groups being revealed and also in becoming aware of the life situation, an insight into the loss of a healthy life but also hope for the future is expressed. The conclusions that could be drawn from this study are that a lifestyle intervention affects health and other important life areas such as the content of daily life and the relationship with the carers, which appears to affect the sense of hope and the ability to see new possibilities. Carers should find situations and activities where the residents and carers participate under equal conditions giving the residents the opportunity to leave the sick roll, experience equality and develop good relationships. PMID- 21029144 TI - Class III atraumatic restorative treatment (ART) in adults living in West Africa- outcomes after 48 months. AB - OBJECTIVES: This observational study assessed the effectiveness of class III restorations using the atraumatic restorative treatment (ART) approach in permanent anterior teeth over a 48-month period. METHODS: Dental auxiliaries placed a total of 117 class III ART restorations in 2004, using a cosmetically improved glass-ionomer (Ionofil(r) Plus; VOCO, Cuxhafen, Germany), in 67 patients with a mean age of 27.3 years in the rural Jahali Health Center, The Gambia. Independent examiners evaluated the restorations after 24 and 48 months using the clinical ART evaluation criteria. RESULTS: Seventy-six of the restorations could be observed over 48 months in 51 patients. After 48 months, 53 of 76 restorations were classified as clinically acceptable (without or with minor intervention (repair) needed), and 23 restorations were classified as insufficient. There was no statistical difference in a clustered performance rating between restorations placed in central and lateral incisors (P=1.0). CONCLUSIONS: The adoption of the ART approach to class III caries cavities made restorative dental care in anterior teeth available in a West African region. The long-term performance was comparable to other studies. Longitudinal clinical studies with greater populations are required to substantiate these results. PMID- 21029145 TI - Maternal self-report of oral health in six-year-old Pacific children from South Auckland, New Zealand. AB - OBJECTIVE: To examine maternal and socio-demographic factors associated with oral health practices and experiences in six-year-old Pacific children. METHODS: The longitudinal Pacific Islands Families (PIF) study is following a cohort of Pacific children born in Auckland, New Zealand in 2000. At approximately six years postpartum maternal reports (n = 1001) on child oral health practices and experiences of fillings and extractions were gathered. RESULTS: Forty-five per cent of mothers reported that their child had experienced fillings or extractions. After adjusting for confounding factors, we found that Tongan children were almost twice as likely to have their teeth filled or extracted than Samoan children (OR, 1.93; 95%, 1.34-2.77). Differences between Samoan children and children of other ethnic groups were not significant. Children of mothers who had secondary qualifications were significantly less likely to have their teeth filled or extracted compared to children of mothers who had postsecondary qualifications (OR, 0.634; 95%, 0.44-0.90). Prolonged duration of breastfeeding was associated with an increased likelihood of filling or extraction experience. In terms of maternal oral hygiene, maternal tooth brushing frequency of less that once a day was significantly associated with increased odds of fillings and/or extractions in their children (OR, 1.35; 95% CI, 1.02-1.79). Children who were sometimes supervised for tooth brushing were significantly more likely to have fillings or extractions than children who were not provided supervision. CONCLUSIONS: These findings highlight the role of cultural factors and maternal hygiene in child oral health outcomes and suggest that health promotion efforts should encompass the whole family and embrace a culturally appropriate approach. PMID- 21029146 TI - The association between low-socioeconomic status mother's Sense of Coherence and their child's utilization of dental care. AB - OBJECTIVES: The objective of this study was to investigate the relationship of low-socioeconomic status mother's Sense of Coherence (SOC) and their child's utilization of dental care services in a city of Southeast Brazil. METHODS: A cross-sectional study was conducted on a sample of 190 schoolchildren aged 11-12 and their mothers in Sao Joao de Meriti-RJ, Southeast Brazil. The outcome variables were children's use of dental care services and visiting dentists mainly for check-ups. Demographic and socioeconomic characteristics and data regarding children's dental care use were collected through interviews with mothers. Children's oral health-related behaviours as well as dental status (DMFS index), dental pain, Visible Dental Plaque and Bleeding on Probing Index were registered. Mother's SOC was assessed through the validated short version (13 item) of Antonovsky's scale. Multiple logistic regression was used in the data analysis. RESULTS: Of the mothers, 81.1% reported on their child's utilization of dental care services. Of them, 42.9% considered check-ups as the main reason for taking their children to dental services. Children whose mothers had higher levels of SOC were more likely to utilize dental care services (OR=2.08 95%CI=1.17-3.64) and visit a dentist mainly for check-ups (except for dental treatment) (OR=2.02 95%CI=1.06-3.81) than those whose mothers had lower levels of SOC. These findings were adjusted for socioeconomic status, children's oral health-related behaviours and oral health measures. CONCLUSIONS: Mother's SOC was a psychosocial factor associated with their child's pattern of use of dental care services in low-socioeconomic status families. PMID- 21029147 TI - Assessing the usefulness of three adjunctive diagnostic devices for oral cancer screening: a probabilistic approach. AB - BACKGROUND AND OBJECTIVE: Visually distinguishing oral cancer from noncancerous oral lesions is problematic. Currently, commercial diagnostic devices are being marketed to dentists as effective screening devices to use in general practice. The purpose of this study is to evaluate the probabilistic performance of VELscope(r), Oral CDx(r) and toluidine blue staining as clinical adjunctive diagnostic procedures in routine screening for oral cancer in dental practice. MATERIALS AND METHODS: Sensitivity and specificity information for each device was taken from the literature. The positive predictive value (PPV) and false positive rate, based on three clinical screening scenario, were calculated using Bayes' Theorem. RESULTS: Under three clinical scenarios (screening the general population, screening only adults (>=40 years) and screening adults (>=40 years) that present with intra-oral visible lesions), VELscope produced the highest PPV's of 1.27%, 2.53% and 8.11%, respectively. This indicates a false positive rate of between 91.89% and 98.73%. CONCLUSION: VELscope, OralCDx and toluidine blue staining have high false positive rates when they are used to screen routinely for oral cancer. It would be inefficient to allocate scarce healthcare resources to the routine use of these devices for oral cancer screening. These devices may be beneficial in opportunistic screening programmes or in cancer referral clinics when the pretest probability of oral cancer is likely to be above 10%. Further research is needed to determine at which pretest probabilities these adjunctive diagnostic devices would be cost-beneficial for the screening of oral cancer. PMID- 21029148 TI - Impact of oral diseases and disorders on oral health-related quality of life of preschool children. AB - BACKGROUND: The presence of oral diseases and disorders can produce an impact on the quality of life of preschool children and their parents, affecting their oral health and well-being. However, socioeconomic factors could confound this association, but it has not been yet tested at this age. OBJECTIVE: To assess the impact of early childhood caries (ECC), traumatic dental injuries (TDI) and malocclusions on the oral health-related quality of life (OHRQoL) of children between 2 and 5 years of age adjusted by socioeconomic factors. METHODS: Parents of 260 children answered the Early Childhood Oral Health Impact Scale (ECOHIS) (six domains) on their perception of the children's OHRQoL and socioeconomic conditions. Two calibrated dentists (kappa>0.8) examined the severity of ECC according to dmft index, and children were categorized into: 0=caries free; 1 5=low severity; >=6=high severity. TDI and malocclusions were examined according to Andreasen & Andreasen (1994) classification and for the presence or absence of three anterior malocclusion traits (AMT), respectively. OHRQoL was measured through ECOHIS domain and total scores, and poisson regression was used to associate the different factors with the outcome. RESULTS: In each domain and overall ECOHIS scores, the severity of ECC showed a negative impact on OHRQoL (P<0.001). TDI and AMT did not show a negative impact on OHRQoL nor in each domain (P>0.05). The increase in the child's age, higher household crowding, lower family income and mother working out of home were significantly associated with OHRQoL (P<0.05). The multivariate adjusted model showed that the high severity of ECC (RR=3.81; 95% CI=2.66, 5.46; P<0.001) was associated with greater negative impact on OHRQoL, while high family income was a protective factor for OHRQoL (RR=0.93; 95% CI=0.87, 0.99; P<0.001). CONCLUSIONS: The severity of ECC and a lower family income had a negative impact on the OHRQoL of preschool children and their parents. PMID- 21029149 TI - Self-assessed masticatory ability and hospitalisation costs among the elderly living independently. AB - The escalating medical costs are a social problem in many countries. Masticatory ability is thought to be related to the general health conditions. The purpose of this study was to show relationships between self-assessed masticatory ability and medical costs among the elderly living independently in community. Data on background factors and self-assessed masticatory ability were collected from 702 Japanese elderly persons by questionnaires. An intra-oral examination was performed to examine the number of remaining teeth. Self-assessed masticatory ability was classified into one of three categories: ability to chew all kinds of food (Good), ability to chew only slightly hard food (Fair) or ability to chew only soft or pureed food (Poor). Data on the annual medical excluding dental costs were obtained from the Japanese National Health Insurance system. The Kruskal-Wallis test was used to examine differences in outpatient costs and hospitalisation costs among the three groups of self-assessed masticatory ability. Univariate unconditional logistic regression models and multivariate logistic regression models were used with medical costs as the dependent variable and self-assessed masticatory ability as the principal independent variable. A significant difference (P=0.039) in hospitalisation costs but not outpatient costs was found among the three groups of self-assessed masticatory ability. The multivariate logistic regression analysis showed that severely impaired masticatory ability (Poor) was significantly related to higher costs of hospitalisation. Self-assessed impairment of masticatory ability may be a significant and independent indicator of higher costs of hospitalisation among community-dwelling elderly persons. PMID- 21029150 TI - Structural, histochemical and immunocytochemical study of the forestomach mucosa in domestic ruminants. AB - The forestomach plays an important role in the digestion physiology of ruminants. The aim of this study is to clarify the morpho-functional role of the mucosa in each of the three compartments of the forestomach in three domestic ruminants species, viz cattle, buffalo and sheep, by means of structural, histochemical and immunocytochemical methods, including transmission electron microscopy, light microscopy and scanning electron microscopy. These methods were chosen to demonstrate the indirect evidence for the presence of nitric oxide (NO) employing NADPHd and nitric oxide synthase I (NOS I). The various cell layers of the forestomach epithelium are described and illustrated in detail. An intense NADPHd staining was observed in the granulosa, spinosa and basal layers of the epithelium, in particular in the cytoplasm over the nucleus. NOS I immunoreactivity was found in all specimens of the forestomach mucosa. The results of this study might reflect a possible role of NO in delaying the onset of cellular apoptosis in the forestomach mucosa of the domestic ruminants, by playing a role in the production of cell energy. PMID- 21029151 TI - Numbers and distribution of immune cells in the tunica mucosa of the small and large intestine of full-thickness biopsies from healthy pet cats. AB - In this study, CD3(+) T lymphocytes and IgA(+) , IgG(+) and IgM(+) plasma cells were quantified in the tunica mucosa of the intestinal tract of 12 pet cats without gastrointestinal diseases. The study included full-thickness biopsies of the duodenum, jejunum, ileum and colon. The distribution and quantification of CD3(+) T cells, IgA(+) , IgG(+) and IgM(+) plasma cells within the intestinal tunica mucosa was performed by using immunohistochemical methods and computer aided morphometry. CD3(+) T cells were significantly prominent in the villi and their numbers increased from duodenum to ileum but decreased towards the colon. The predominant type of plasma cells was IgA(+) cells, followed by IgM(+) cells. The number of IgG(+) cells was generally low compared to the other plasma cell types investigated. The results of the vertical distribution showed that IgA(+) and IgM(+) plasma cells were most numerous in the lower crypt areas, whilst IgG(+) plasma cells accumulated in the upper crypt region with a decline towards the villi and the lower crypt areas of control cats. All types of plasma cells showed a general decline from the duodenum towards the caudal sections of the intestinal tract regarding the horizontal distribution of plasma cells. This study provides a comprehensive overview on the vertical and horizontal distribution and the number of CD3(+) T cells and IgA(+) , IgG(+) and IgM(+) plasma cells in the intestinal tunica mucosa of pet cats. PMID- 21029152 TI - Copper ions potentiate organic hydroperoxide and hydrogen peroxide toxicity through different mechanisms in Xanthomonas campestris pv. campestris. AB - Copper (Cu)-based biocides are important chemical controls for both fungal and bacterial diseases in crop fields. Here, we showed that Cu ions at a concentration of 100 MUM enhanced t-butyl hydroperoxide (tBOOH) and hydrogen peroxide (H(2) O(2) ) killing of Xanthomonas campestris pv. campestris through different mechanisms. The addition of an antilipid peroxidation agent (alpha tocopherol) and hydroxyl radical scavengers (glycerol and dimethyl sulphoxide) partially protected the bacteria from the Cu-enhanced tBOOH and H(2) O(2) killing, respectively. Inactivation of the alkyl hydroperoxide reductase gene rendered the mutant vulnerable to lethal doses of copper sulphate, which could be alleviated by the addition of an H(2) O(2) scavenger (pyruvate) and alpha tocopherol. Taken together, the data suggest that Cu ions influence the killing effect of tBOOH through the stimulation of lipid peroxidation, while hydroxyl radical production is the underlying mechanism responsible for the Cu-ion enhanced H(2) O(2) killing effects. PMID- 21029153 TI - Construction and characterization of Enterococcus faecalis CG110/gfp/pRE25*, a tool for monitoring horizontal gene transfer in complex microbial ecosystems. AB - Enterococci are among the most notorious bacteria involved in the spread of antibiotic resistance (ABR) determinants via horizontal gene transfer, a process that leads to increased prevalence of antibiotic-resistant bacteria. In complex microbial communities with a high background of ABR genes, detection of gene transfer is possible only when the ABR determinant is marked. Therefore, the conjugative multiresistance plasmid pRE25, originating from a sausage-associated Enterococcus faecalis, was tagged with a 34-bp random sequence marker spliced by tet(M). The plasmid constructed, designated pRE25(*) , was introduced into E. faecalis CG110/gfp, a strain containing a gfp gene as chromosomal marker. The plasmid pRE25(*) is fully functional compared with its parental pRE25, occurs at one to two copies per chromosome, and can be transferred to Listeria monocytogenes and Listeria innocua at frequencies of 6 * 10(-6) to 8 * 10(-8) transconjugants per donor. The markers on the chromosome and the plasmid enable independent quantification of donor and plasmid, even if ABR genes occur at high numbers in the background ecosystem. Both markers were stable for at least 200 generations, permitting application of the strain in long-running experiments. Enterococcus faecalis CG110/gfp/pRE25(*) is a potent tool for the investigation of horizontal ABR gene transfer in complex environments such as food matrices, biofilms or colonic models. PMID- 21029154 TI - Perceived sleep quality among edentulous elders. AB - BACKGROUND: Anatomical changes associated with edentulism are thought to disturb seniors' sleep. OBJECTIVES: (1) To determine sleep quality and daytime sleepiness of edentulous elders. (2) To examine the association between oral health-related quality of life and sleep quality. METHODS: Data were collected at a 1-year follow-up from 173 healthy edentulous elders who had participated in a randomised controlled trial and randomly received two types of mandibular prosthesis. Subjective sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI, range 0-21), with higher scores indicating poorer sleep quality. The Epworth Sleepiness Scale (ESS) was used to measure the level of perceived daytime sleepiness, and scores >=10 indicated sleepiness. RESULTS: The mean global PSQI and ESS scores were 4.7 +/- 3.5 and 5.3 +/- 3.9. There were no differences in sleep quality or sleepiness between those who wore their dentures at night and those who did not. Elders with frequent denture problems were sleepier during the day than those with fewer problems (p = 0.0034). General health (p = 0.02) and oral health-related quality of life (p = 0.001) are significant predictors of sleep quality. CONCLUSION: Healthy edentulous elders, independent of nocturnal wearing of their prosthesis, are good sleepers. Maintaining high oral health quality of life could contribute to better sleep. PMID- 21029155 TI - Oral myiasis in an elderly patient. AB - BACKGROUND: Myiasis is the invasion of living tissue of humans and other mammals by eggs or maggots of flies of the order of Diptera. It occurs mainly in the Tropics and is associated with inadequate public and personal hygiene. Oral myiases in an older man appears to be rare. OBJECTIVE: To relate a case of oral myiases in a debilitated older man treated by mechanical removal of the maggots, identifying the adult insect that caused the infestation. METHODS: The diagnosis of oral myiasis was established by the clinical examination and it was detected that the infestation involved only soft tissue and the sinus cavity. The patient was submitted to two mechanical removal of the visible maggots. RESULTS: Total of 110 maggots was removed from the oral cavity of the patient and adult insects was identified as belonging to the Calliphoridae Family, Cochliomyia hominivorax species. The patient died two days after the second procedure by severe systemic complications. CONCLUSIONS: The mechanic removal and the identification of the maggots must be adopted as soon as possible to prevent further tissue damage and bacterial infection in cases of oral myiasis. Special attention should be given to the debilitated old patients that are particularly susceptible to oral myiasis infestation. PMID- 21029156 TI - Update on the use of melatonin in pediatrics. AB - Melatonin, an endogenously produced indoleamine, is a highly effective antioxidant, free radical scavenger, and a primary circadian regulator. Melatonin has important antioxidant properties owing to direct and indirect effects. It directly scavenges reactive oxygen and reactive nitrogen species, prevents molecular oxidation, improves mitochondrial physiology, and restores glutathione homeostasis. Its indirect antioxidant effects stem from its ability to stimulate the activities of the enzymes involved in the glutathione cycling and production. Melatonin, by reducing free radical damage, may be an effective protective agent for the fetus as it is in adults. Several clinical studies on melatonin have shown that it reduces oxidative stress in human newborns with sepsis, hypoxic distress, or other conditions, where there is excessive free radical generation. A role of melatonin in infant development has also been suggested. Pineal dysfunction may be associated with deleterious outcomes in infants and may contribute to an increased prevalence of sudden infant death syndrome. Delayed melatonin production is evident in infants who had experienced an apparent life threatening event. Melatonin has been used as a pharmacologic treatment for insomnias associated with shift work, jet lag, and delayed sleep onset in adults for decades. In children as well, melatonin has value as a sleep-promoting agent. Evidence suggests that melatonin has utility as an analgesic agent presumably related to its ability to release beta-endorphin. The data support the notion that melatonin, or one of its analogs, might find use as an anesthetic agent in children. PMID- 21029157 TI - Prevalence and procedural outcomes of percutaneous coronary intervention and coronary artery bypass grafting in patients with diabetes and multivessel coronary artery disease. AB - BACKGROUND: Percutaneous coronary intervention (PCI) is used with increasing frequency in patients with diabetes and multivessel disease. This study investigated evolving revascularization strategies in the State of Washington. METHODS: The Clinical Outcomes Assessment Program captures all revascularization in the State of Washington and was used to compare diabetic patients with multivessel disease undergoing first-time revascularization from 1999 to 2007. Categorical variables were compared with the chi-squared test and continuous variables were compared with the student's t-test. Results were risk-adjusted using a logistic regression. RESULTS: A total of 11,602 patients with diabetes and multivessel disease underwent revascularization from 1999 to 2007 and were nearly equally divided between coronary artery bypass grafting (CABG) (51%) and PCI (49%). Patients undergoing CABG had a higher (p < 0.0001) prevalence of congestive heart failure, cerebrovascular disease, peripheral vascular disease, three-vessel coronary artery disease (CAD), and intraaortic balloon pump insertion, but a lower prevalence of female gender, cardiogenic shock, and emergency procedures. Patients undergoing CABG had more (p < 0.0001) three-vessel CAD and more complete revascularization (3.7 vs. 1.5 lesions treated). Short-term risk-adjusted mortality was equivalent. The prevalence of PCI increased from 34.1% in 1999 to 59.4% in 2007. CONCLUSIONS: PCI is applied with increasing frequency to patients with diabetes mellitus (DM) and multivessel disease. PCI is used most commonly in two-vessel CAD or with acute coronary syndromes with more limited and targeted revascularization. CABG is more commonly applied to extensive disease with more complete revascularization. Both the prevalence and percentage of patients undergoing PCI as primary therapy for multivessel disease with DM is increasing. A multidisciplinary approach may be warranted to ensure optimal outcomes. PMID- 21029158 TI - Coronary revascularization for absent left main artery. PMID- 21029159 TI - Intercostal artery aneurysm associated with coarctation of aorta in an adult. AB - Intercostal artery aneurysms associated with coarctation of aorta (CoA) are rare and their natural histories are poorly understood. This report describes the surgical correction of this anomaly in an adult without performing extracorporeal circulation. The coarctated segment of aorta and intercostal artery aneurysm were resected, and the continuity of the descending aorta was reestablished with an interposed vascular graft. PMID- 21029160 TI - Coronary artery bypass grafting in adults with congenital heart disease. AB - BACKGROUND: Adults with congenital heart disease (CHD) and coronary artery disease (CAD) have unique clinical manifestation due to the coexistence of intracardiac anomalies and CAD. Case reports are rare in surgical management of CHD combined with CAD. Our goal is to study the outcome of surgical intervention of CHD and CAD concomitantly. METHODS: From February 2002 to August 2009, 29 adult patients underwent coronary artery bypass grafting (CABG) and surgical correction of CHD concomitantly. Congenital cardiac anomalies include atrial septal defect (ASD) in 21 cases, ventricular septal defect in four cases, atrioventricular septal defect in three cases, and cor triatriatum in one case. Coronary angiography demonstrated: one-vessel disease in 10 cases, two-vessel disease in 11 cases, and three-vessel disease in eight cases. Coronary revascularization and intracardiac anomalies were corrected with cardiopulmonary bypass in 23 cases. There were six patients who had off-pump coronary artery pass grafting (OPCAB) and intraoperative device closure of ASD. RESULTS: One patient died of pulmonary infection and multiorgan failure. Follow-up time was from 2 to 89 months (mean, 42 +/- 25 months). One patient with recurrent angina did not need intervention of the revascularization. Six patients who acquired OPCAB and intraoperative device closure of ASD had no complications after surgery. CONCLUSIONS: Surgery for adult patients who had CHD with CAD was a safe and effective management. OPCAB with intraoperative device closure of ASD was a reasonable approach for some selective patients. PMID- 21029161 TI - Using conservation evidence to guide management. PMID- 21029162 TI - Effectiveness of scat-detection dogs in determining species presence in a tropical savanna landscape. AB - Most protected areas are too small to sustain populations of wide-ranging mammals; thus, identification and conservation of high-quality habitat for those animals outside parks is often a high priority, particularly for regions where extensive land conversion is occurring. This is the case in the vicinity of Emas National Park, a small protected area in the Brazilian Cerrado. Over the last 40 years the native vegetation surrounding the park has been converted to agriculture, but the region still supports virtually all of the animals native to the area. We determined the effectiveness of scat-detection dogs in detecting presence of five species of mammals threatened with extinction by habitat loss: maned wolf (Chrysocyon brachyurus), puma (Puma concolor), jaguar (Panthera onca), giant anteater (Myrmecophaga tridactyla), and giant armadillo (Priodontes maximus). The probability of scat detection varied among the five species and among survey quadrats of different size, but was consistent across team, season, and year. The probability of occurrence, determined from the presence of scat, in a randomly selected site within the study area ranged from 0.14 for jaguars, which occur primarily in the forested areas of the park, to 0.91 for maned wolves, the most widely distributed species in our study area. Most occurrences of giant armadillos in the park were in open grasslands, but in the agricultural matrix they tended to occur in riparian woodlands. At least one target species occurred in every survey quadrat, and giant armadillos, jaguars, and maned wolves were more likely to be present in quadrats located inside than outside the park. The effort required for detection of scats was highest for the two felids. We were able to detect the presence for each of five wide-ranging species inside and outside the park and to assign occurrence probabilities to specific survey sites. Thus, scat dogs provide an effective survey tool for rare species even when accurate detection likelihoods are required. We believe the way we used scat detection dogs to determine the presence of species can be applied to the detection of other mammalian species in other ecosystems. PMID- 21029163 TI - Using parasitic trematode larvae to quantify an elusive vertebrate host. AB - Digenean trematode parasites require multiple host species to complete their life cycles, and their abundance can often be strongly correlated with the abundance of their host species. Species richness and abundance of parasites in easily sampled host species may yield an accurate estimate of the species richness and abundance of other hosts in a parasite's life cycle that are difficult to survey directly. Accordingly, we investigated whether prevalence and mean abundance of trematodes could be used to estimate the abundance of one of their host species, diamondback terrapins (Malaclemys terrapin), which are difficult to sample and are designated as near threatened (by the International Union for Conservation of Nature [IUCN Red List]) along some U.S. coasts. As an adult the trematode Pleurogonius malaclemys is specific to terrapins. Its larval stages live first inside mud snails (Ilyanassa obsoleta) and are subsequently shed into the environment where they form external metacercarial cysts on hard surfaces such as snail opercula. The life cycle of P. malaclemys is completed when terrapins ingest these cysts. At 12 sites along the coast of Georgia (U.S.A.), we determined the prevalence of internal P. malaclemys larvae in mud snails (proportion of infected snails in a population) and the prevalence and mean abundance of external trematode cysts. We examined whether these data were correlated with terrapin abundance, which we estimated with mark-recapture methods. The abundance of external cysts and salinity explained >=59% of the variability in terrapin abundance. We suggest that dependent linkages between the life stages of multihost parasites make them reliable predictors of host species' abundance, including hosts with abundances that are challenging to quantify directly. PMID- 21029164 TI - Defining "rural" for veterans' health care planning. AB - PURPOSE: The Veterans Health Administration (VHA) devised an algorithm to classify veterans as Urban, Rural, or Highly Rural residents. To understand the policy implications of the VHA scheme, we compared its categories to 3 Office of Management and Budget (OMB) and 4 Rural-Urban Commuting Area (RUCA) geographical categories. METHOD: Using residence information for VHA health care enrollees, we compared urban-rural classifications under the VHA, OMB, and RUCA schemes; the distributions of rural enrollees across VHA health care networks (Veterans Integrated Service Networks [VISNs]); and how each scheme indicates whether VHA standards for travel time to care are met for the most rural veterans. RESULTS: VHA's Highly Rural and Urban categories are much smaller than the most rural or most urban categories in the other schemes, while its Rural category is much larger than their intermediate categories. Most Highly Rural veterans live in VISNs serving the Rocky Mountains and Alaska. Veterans defined as the most rural by RUCA or OMB are distributed more evenly across most VISNs. Nearly all urban enrollees live within VHA standards for travel time to access VHA care; so do most enrollees defined by RUCA or OMB as the most rural. Only half of Highly Rural enrollees, however, live within an hour of primary care, and 70% must travel more than 2 hours to acute care or 4 hours to tertiary care. CONCLUSIONS: VHA's Rural category is very large and broadly dispersed; policy makers should supplement analyses of Rural veterans' health care needs with more detailed breakdowns. Most of VHA's Highly Rural enrollees live in the western United States where distances to care are great and alternative delivery systems may be needed. PMID- 21029165 TI - Mortality and revascularization following admission for acute myocardial infarction: implication for rural veterans. AB - INTRODUCTION: Annually, over 3,000 rural veterans are admitted to Veterans Health Administration (VA) hospitals for acute myocardial infarction (AMI), yet no studies of AMI have utilized the VA rural definition. METHODS: This retrospective cohort study identified 15,870 patients admitted for AMI to all VA hospitals. Rural residence was identified by either Rural-Urban Commuting Area (RUCA) codes or the VA Urban/Rural/Highly Rural (URH) system. Endpoints of mortality and coronary revascularization were adjusted using administrative laboratory and clinical variables. RESULTS: URH codes identified 184 (1%) veterans as highly rural, 6,046 (39%) as rural, and 9,378 (60%) as urban; RUCA codes identified 1,350 (9%) veterans from an isolated town, 3,505 (22%) from a small or large town, and 10,345 (65%) from urban areas. Adjusted mortality analyses demonstrated similar risk of mortality for rural veterans using either URH or RUCA systems. Hazards of revascularization using the URH classification demonstrated no difference for rural (HR, 0.96; 95% CI, 0.94-1.00) and highly rural veterans (HR, 1.13; 0.96-1.31) relative to urban veterans. In contrast, rural (relative to urban) veterans designated by the RUCA system had lower rates of revascularization; this was true for veterans from small or large towns (HR, 0.89; 0.83-0.95) as well as veterans from isolated towns (HR, 0.86; 0.78-0.93). CONCLUSION: Rural veterans admitted for AMI care have a similar risk of 30-day mortality but the adjusted hazard for receipt of revascularization for rural veterans was dependent upon the rural classification system utilized. These findings suggest potentially lower rates of revascularization for rural veterans. PMID- 21029166 TI - Impact of rural residence on survival of male veterans affairs patients after age 65. AB - OBJECTIVES: More than 1 in 5 Veterans Affairs (VA) users lives in a rural setting. Rural veterans face different barriers to health care than their urban counterparts, but their risk of death relative to their urban counterparts is unknown. The objective of our study was to compare survival between rural and urban VA users. METHODS: We linked the Large Health Survey of Veteran Enrollees conducted in 1999 to the Veterans Administration vital status registry. We used time-to-event regression models controlling for patient race, education, ZIP-code median income, and marital and smoking status. FINDINGS: Of the 372,463 male veterans of age 65 or greater, 80,931 lived in rural settings. Age-adjusted mortality was 5.9% higher (95% CI, 4.5%-7.2%) in rural residents compared to urban residents. After adjusting for age, education, and ZIP-code median income, rural residents had 3.0% lower mortality (95% CI, 1.5%-4.4%). Compared to urban and suburban VA users, rural VA users' mortality at age 65 was 12% lower, but this advantage gradually diminished by age 75. CONCLUSION: Mortality after the age of 65 for male VA users is higher in rural dwellers than in urban dwellers. However, among veterans of the same socioeconomic characteristics, rural-dwelling veterans have up to 15% better mortality than urban-dwelling veterans until the age of 75. PMID- 21029167 TI - Reaching out to older veterans in need: the Elko clinic demonstration project. AB - CONTEXT: The challenge of providing meaningful health care services to veterans living in rural communities is a major public health concern that involves redefining the traditional facility-based model of care delivery employed in urban areas. PURPOSE: This paper describes the steps of a demonstration project, the Elko Telehealth Outreach Clinic. The clinic, located in Elko, Nevada, was created to meet the health care needs of veterans who expressed a desire for greater access to VA services. METHODS: The Elko Telehealth Outreach Clinic is a specific example of the real-life implementation of the community-as-partner model as an operational framework for coordinating local, regional, and VA resources. The Elko Clinic provides a limited set of health care services including medication management, health education, prescription refills, routine lab tests, and specialty services through telehealth. FINDINGS: From December 2006 to December 2007, a total of 84 unique veterans received health care services through the Elko Clinic. CONCLUSIONS: Our findings support the usefulness of an expanded community-as-partner model to guide a process for addressing the health care needs of veterans in Elko, Nevada, and they have implications for the development and maintenance of outreach clinics in other rural settings. PMID- 21029168 TI - The rural-urban divide: health services utilization among older Mexicans in Mexico. AB - CONTEXT: Mexico. PURPOSE: Using the health care service utilization model as a framework, this paper will analyze the differences in health care service use among older Mexicans living in urban and rural areas in Mexico. METHODS: The Mexican Health and Aging Survey (MHAS) data were used to test the applicability of Andersen's "model of health services" of predisposing (ie, age, sex, etc.), enabling (education, insurance coverage, etc.) and need factors (diabetes, hypertension, etc.) to predict ever being in the hospital and physician visits in the past year by place of residence (urban, rural, semi-rural). FINDINGS: Results showed that older Mexicans living in the most rural areas (populations of 2,500 or fewer) were significantly less likely to have been hospitalized in the previous year and visited the physician less often (P < .0001) than their urban counterparts. The significant difference in hospitalization between rural and urban residing older Mexicans was largely accounted for by having health care coverage. Certain need factors such as diabetes, previous heart attack, hypertension, depression, and functional limitations predicted frequency of physician visits and hospitalization, but they did not explain variations between rural and urban older Mexicans. CONCLUSIONS: Not having insurance coverage was associated with a lower likelihood of spending an overnight visit in the hospital and visiting a physician for older Mexicans. This lower utilization may be due to barriers to access rather than better health. PMID- 21029169 TI - Having a diagnosis of diabetes is not associated with general diabetes knowledge in rural Hispanics. AB - PURPOSE: The prevalence of diabetes among Hispanics in Washington State is 30% greater than it is for non-Hispanic whites. Hispanics also have higher rates of diabetes-related complications and mortality due to the disease. Although interventions have been developed for the Hispanic community, studies in rural settings are limited. To address this we conducted a study to identify factors associated with general diabetes knowledge in a rural Hispanic population. METHODS: This study was conducted as part of a larger project in partnership with a local community hospital in Washington State's Lower Yakima Valley. Diabetes knowledge was assessed as part of a screening survey using 5 statements selected from the Diabetes Knowledge Questionnaire. Men and women (N = 1,297) between the ages of 18 and 92 attending community-oriented events took part in the survey. Gender, education, age, birthplace, diabetic status, and family history of diabetes were tested as predictors of diabetes knowledge. FINDINGS: Overall, general knowledge was high with 71%-84% of participants responding correctly to 4 of 5 statements, while only 17% of participants responded correctly to a fifth statement. Although no variable was associated with all statements, family history, gender, and education were most frequently associated with knowledge. Diabetic status, age, and birthplace were less often or not associated with the knowledge statements. CONCLUSION: Contrary to expectations, having a diagnosis of diabetes was not among the factors most frequently associated with diabetes knowledge. Future research should investigate the roles of family history, gender, and diabetic status as conduits of diabetes education among rural Hispanics. PMID- 21029170 TI - An examination of triple jeopardy in rural youth physical activity participation. AB - PURPOSE: Chances for a healthy life are not equally distributed across society. Instead, genetic, social, and environmental factors help determine the probability that a child will be healthy and active. We investigate the probability that youth will be physically active by examining 3 consistent correlates of physical activity. The individual and interaction effects of self efficacy, social support, and access to physical activity areas are used to predict rural youth physical activity participation. We hypothesize that youth lacking all 3 activity supports will be in "triple jeopardy" for physical activity participation. METHODS: Data were collected using a researcher administered questionnaire with 147 youth in 2004. Youth ages 9-18 were enrolled in grades 4, 7, and 11 in 2 diverse rural counties in Georgia. FINDINGS: Overall, a greater number of disadvantageous statuses were related to a lower probability of physical activity participation. Low self-efficacy, low social support, and no access to physical activity areas were related to lower levels of physical activity participation among rural youth. These variables exerted a stronger impact when factors were allowed to interact than when their isolated effects were summed. CONCLUSIONS: This study assessed correlates of physical activity among rural youth. These investigations, while scarce, can help identify subgroups of the population that may need to be targeted for intervention. Findings indicate that lived experience of youth (captured by the interaction of physical activity correlates) may be critical for understanding patterns of active and sedentary living. PMID- 21029171 TI - Rural-urban disparities in child abuse management resources in the emergency department. AB - PURPOSE: To characterize differences in child abuse management resources between urban and rural emergency departments (EDs). METHODS: We surveyed ED directors and nurse managers at hospitals in Oregon to gain information about available abuse-related resources. Chi-square analysis was used to test differences between urban and rural EDs. Multivariate analysis was performed to examine the association between a variety of hospital characteristics, in addition to rural location, and presence of child abuse resources. FINDINGS: Fifty-five Oregon hospitals were surveyed. A smaller proportion of rural EDs had written abuse policies (62% vs 95%, P= .006) or on-site child abuse advocates (35% vs 71%, P= .009). Thirty-two percent of rural EDs had none of the examined abuse resources (vs 0% of urban EDs, P= .01). Of hospital characteristics studied in the multivariate model, only rural location was associated with decreased availability of child abuse resources (OR 0.19 [95% CI, 0.05-0.70]). CONCLUSIONS: Rural EDs have fewer resources than urban EDs for the management of child abuse. Other studied hospital characteristics were not associated with availability of abuse resources. Further work is needed to identify barriers to resource utilization and to create resources that can be made accessible to all ED settings. PMID- 21029172 TI - Impact of long farm working hours on child safety practices in agricultural settings. AB - OBJECTIVES: To characterize working hours of adult farm owner-operators and their spouses by season, and to examine associations between working hours and farm safety practices affecting children. METHODS: We conducted a secondary analysis of cross-sectional survey data collected as part of an existing study of injury and its determinants. RESULTS: Owner-operators reported a median of 60 to 70 hours of farm work per week during warm weather months, with declines in hours over the winter. Spouses reported similar seasonal patterns, although their median reported hours were much lower. Longer farm working hours by owner operators were marginally associated with increased exposure of teenagers to farm work hazards. Exposures of young children to worksite hazards rose in association with longer farm working hours by spouses. CONCLUSION: Exposures of children to farm worksite hazards and demands may be consequences of adult long working hours. PMID- 21029173 TI - County-level poverty is equally associated with unmet health care needs in rural and urban settings. AB - CONTEXT: Regional poverty is associated with reduced access to health care. Whether this relationship is equally strong in both rural and urban settings or is affected by the contextual and individual-level characteristics that distinguish these areas, is unclear. PURPOSE: Compare the association between regional poverty with self-reported unmet need, a marker of health care access, by rural/urban setting. METHODS: Multilevel, cross-sectional analysis of a state representative sample of 39,953 adults stratified by rural/urban status, linked at the county level to data describing contextual characteristics. Weighted random intercept models examined the independent association of regional poverty with unmet needs, controlling for a range of contextual and individual-level characteristics. FINDINGS: The unadjusted association between regional poverty levels and unmet needs was similar in both rural (OR = 1.06 [95% CI, 1.04-1.08]) and urban (OR = 1.03 [1.02-1.05]) settings. Adjusting for other contextual characteristics increased the size of the association in both rural (OR = 1.11 [1.04-1.19]) and urban (OR = 1.11 [1.05-1.18]) settings. Further adjustment for individual characteristics had little additional effect in rural (OR = 1.10 [1.00 1.20]) or urban (OR = 1.11 [1.01-1.22]) settings. CONCLUSIONS: To better meet the health care needs of all Americans, health care systems in areas with high regional poverty should acknowledge the relationship between poverty and unmet health care needs. Investments, or other interventions, that reduce regional poverty may be useful strategies for improving health through better access to health care. PMID- 21029174 TI - Pollution sources and mortality rates across rural-urban areas in the United States. AB - PURPOSE: To conduct an assessment of rural environmental pollution sources and associated population mortality rates. METHODS: The design is a secondary analysis of county-level data from the Environmental Protection Agency (EPA), Department of Agriculture, National Land Cover Dataset, Energy Information Administration, Centers for Disease Control and Prevention, the US Census, and others. We described the types of pollution sources present in metropolitan and nonmetropolitan counties and examined the associations between these sources and rates of all-cause, cardiovascular, respiratory, and cancer mortality while controlling for age, race, and other covariates. FINDINGS: Rural counties had 65,055 EPA-monitored pollution discharge sites. As expected, rural counties had significantly greater exposure to potential agriculture-related pollution. Regression models specific to rural counties indicated that greater density of water pollution sources was significantly associated with greater total and cancer mortality. Rural air pollution sources were associated with greater cancer mortality rates. Rural coal mining areas had higher total, cancer, and respiratory disease mortality rates. Agricultural production was generally associated with lower mortality rates. Greater levels of human development were significantly related to higher adjusted total and cancer mortality. CONCLUSIONS: The association between pollution sources and mortality risk is not a phenomenon limited to metropolitan areas. Results carry policy implications regarding the need for effective environmental standards and monitoring. Further research is needed to better understand the types and distributions of pollution in rural areas, and the health consequences that result. PMID- 21029175 TI - Choice of personal assistance services providers by medicare beneficiaries using a consumer-directed benefit: rural-urban differences. AB - PURPOSE: To examine the impact of an experimental consumer-choice voucher benefit on the selection of independent and agency personal assistance services (PAS) providers among rural and urban Medicare beneficiaries with disabilities. METHODS: The Medicare Primary and Consumer-Directed Care Demonstration enrolled 1,605 Medicare beneficiaries in 19 counties in New York State, West Virginia, and Ohio. A total of 839 participants were randomly assigned to receive a voucher benefit (up to $250 per month with a 20% copayment) that could be used toward PAS provided by either independent or agency workers. A bivariate probit model was used to estimate the probabilities of choosing either type of PAS provider while controlling for potential confounders. FINDINGS: The voucher was associated with a 32.4% (P < .01) increase in the probability of choosing agency providers and a 12.5% (P= .03) increase in the likelihood of choosing independent workers. When the analysis was stratified by rural/urban status, rural voucher recipients had 36.8% higher probability of using independent workers compared to rural controls. Urban voucher recipients had 37.1% higher probability of using agency providers compared to urban controls. CONCLUSIONS: This study provided evidence that rural and urban Medicare beneficiaries with disabilities may have very different responses to a consumer-choice PAS voucher program. Offering a consumer-choice voucher option to rural populations holds the potential to significantly improve their access to PAS. PMID- 21029176 TI - Does rurality affect quality of life following treatment for breast cancer? AB - PURPOSE: The present research examined the extent to which rural residence and social support seeking are associated with quality of life (QOL) among breast cancer patients following chemotherapy. METHODS: Female breast cancer patients (n = 46) from communities of varying degrees of rurality in a Midwestern state completed psychological and QOL measures at 1-month postchemotherapy. Analyses assessed the relationships between QOL outcomes, rurality, and social support seeking. FINDINGS: Using age and education as covariates, regression analyses were conducted to determine the extent to which QOL was related to social support seeking and rural/urban residence. Analyses revealed that social support seeking was associated with lower scores on multiple indices of QOL, and it was associated with higher self-reported symptoms of depression. Several significant associations with rural/urban residence were noted as well. Specifically, increasing rurality, as defined by USDA Rural-Urban continuum codes, was associated with lower overall QOL, lower functional well-being, and increased complaints of breast cancer specific symptoms. CONCLUSIONS: These findings highlight the relevance of continued efforts to address social support needs among women with a history of breast cancer living in rural and urban communities. They also suggest that individuals in more rural communities may be at risk for lowered QOL in the early period following cancer treatment. Future research is needed to replicate these results with larger and more diverse samples of rural and urban dwelling individuals, and to determine whether these effects may be attributed to identifiable characteristics of rural communities (eg, fewer cancer-related resources). PMID- 21029177 TI - Pheochromocytoma presenting with Takotsubo syndrome. AB - The clinical presentation of Takotsubo syndrome, or apical ballooning syndrome, resembles an extensive anterolateral myocardial infarction with chest pain symptoms and electrocardiographic ST-elevation or T-wave inversion noted in most patients. However, coronary arteries are invariably found to be normal or to display minimal atherosclerotic disease despite modest elevation of cardiac enzymes. Since most cases of Takotsubo syndrome occur after intense physical and/or emotional stress, catecholamine surge appears to be a common underlying mechanism. We present a case of Takotsubo syndrome, which presented with unusual symptoms and was found to be caused by pheochromocytoma. A sudden rise in blood pressure moments after completion of echocardiographic stress testing aided in uncovering the diagnosis. PMID- 21029179 TI - Clinical utility of intravascular ultrasound in the assessment of coronary allograft vasculopathy: a review. AB - Coronary artery vasculopathy (CAV) is one of the major factors that limit the long-term survival of heart transplant recipients. It is difficult to diagnose CAV, especially in the early stages. Traditional coronary angiography has been used for the diagnosis of CAV, but this method has limitations. Current literature suggests that intravascular ultrasound (IVUS) is a safe imaging technique that is beneficial for the early diagnosis of CAV; in comparison, IVUS with virtual histology (IVUS-VH) is an even more promising diagnostic utility. Despite its advantages, IVUS is currently not routinely utilized as the primary diagnostic modality for CAV in heart transplant recipients. In this review, we evaluate and summarize the clinical utility of IVUS in the early diagnosis of CAV, including its utility for assessing vessel remodeling, plaque composition, and prognostic value; morphometric analysis; and guiding therapy. After reviewing the relevant published literature, it is our recommendation that the use of IVUS be considered in all post-transplant CAV screening. PMID- 21029178 TI - An intravascular ultrasound analysis in women experiencing chest pain in the absence of obstructive coronary artery disease: a substudy from the National Heart, Lung and Blood Institute-Sponsored Women's Ischemia Syndrome Evaluation (WISE). AB - AIMS: Using intravascular ultrasound (IVUS), we sought to characterize coronary morphology in women with chest pain without major epicardial obstructive coronary artery disease (CAD). We have previously observed an unexpectedly high rate of adverse outcomes among women with chest pain and normal or insignificant obstructive CAD. Information about the presence and characteristics of coronary atherosclerosis in these women could provide insight into the mechanisms related to increased risk, as well as improved diagnosis, prevention, and treatment. METHODS: Women (n = 100) with suspected ischemia without obstructive CAD (>50% stenosis) underwent IVUS of a left coronary segment with measurements by a core lab masked to clinical and angiographic findings. RESULTS: Angiograhic core lab analysis found 69.6% of patients had no (<=20%) and 30.4% had minimal (20-<50%) CAD. IVUS segmental images were interpretable by the core lab in 92 women, with 19 (21%) having no atherosclerosis (intimal-medial thickness <0.5 mm). In the remaining 73 women (79%), percent atheroma volume was 27 +/- 8% and mean maximum plaque thickness was 0.53 +/- 0.22 mm. Thirty-eight women with atherosclerosis (53%) had >=30% of interrogated vessel involved. The average vessel involvement was 40%, and the maximum plaque thickness was 1.27 mm. The number of risk factors strongly correlated with percent atheroma volume (r = 0.53, P < 0.0001) and percent vessel involvement (r = 0.51, P < 0.0001), with the strongest independent predictor of both being age. Remodeling was assessed in 59/73 women (81%), and 73% had evidence of positive remodeling. CONCLUSIONS: In symptomatic women without significant luminal obstructive CAD, we observed a high prevalence of atherosclerosis with positive remodeling and preserved lumen size. These findings may help explain increased risk and emphasize need for improved diagnostic and treatment options for women with concealed CAD. PMID- 21029180 TI - A comparative immunohistochemical evaluation of CD68 and TRAP protein expression in central and peripheral giant cell granulomas of the jaws. AB - BACKGROUND: Giant cell granulomas of the jaws are lesions that arise either peripherally in periodontal ligament and mucoperiosteum or centrally in the bone. The aim of this study was to evaluate expression of CD68 and tartrate-resistant acid phosphatase (TRAP) proteins in multinucleated giant cells and mononuclear cells. METHODS: Formalin-fixed and paraffin-embedded tissue section of 20 specimens of central giant cell granuloma and 20 cases of peripheral giant cell granuloma were immunohistochemically analyzed for CD68 and TRAP proteins expression rate using Biotin-Streptavidin method. RESULT: In central giant cell granuloma, more than 99% of multinucleated giant cells were positive for TRAP antibody and about 90% were positive for CD68. In mononuclear cells of this lesion, 14% of cases were positive with TRAP antibody and 8% with CD68. In peripheral giant cell granuloma, TRAP antibody was positive in 99% of giant cells and in 13% of mononuclear cells. A proportion of 97% of giant cells and 6% of mononuclear cells reacted positively with CD68. CONCLUSION: Immunohistochemical evidence of this study shows that giant cells and a group of mononuclear cells of stroma in both peripheral and central giant cell granuloma express TRAP antibody severely that is specific for osteoclast. Also, these cells are positive reactive to CD68, which is the macrophage marker and therefore it can be mentioned that giant cells are osteoclast, although their origins are macrophagic/monocytic or their precursors, and maybe mononuclear cells in stroma have a role in formation of giant cells. PMID- 21029181 TI - Expression of DNA repair proteins, MSH2, MLH1 and MGMT in mobile tongue squamous cell carcinoma: associations with clinicopathological parameters and patients' survival. AB - BACKGROUND: DNA repair is a major defense mechanism, which contributes to the maintenance of genetic sequence, minimizing cell death, mutation rates, replication errors, DNA damage persistence and genomic instability. Alterations of proteins participating in DNA repair mechanisms have been associated with several aspects of cancer biology. The present study aimed to evaluate the clinical significance of DNA repair proteins, MSH2, MLH1 and MGMT in mobile tongue squamous cell carcinoma (SCC). METHODS: MSH2, MLH1 and MGMT protein expression was assessed immunohistochemically on 49 mobile tongue SCC tissue samples and was analyzed in relation with clinicopathological characteristics, overall and disease-free patients' survival. RESULTS: MSH2 expression was significantly associated with depth of invasion (P=0.0335), tumor shape (P=0.0396) and muscular invasion (P=0.0098). MLH1 expression was significantly associated with lymph node metastases (P=0.0484) and borderline with perineural invasion (P=0.0699). MGMT expression was significantly associated with depth of invasion (P=0.0472), tumor shape (P=0.0187), perineural invasion (P=0.0115) and lymph node metastases (P=0.0032) and borderline with vascular invasion (P=0.0755). MSH2 expression was significantly associated with disease-free patients' survival in univariate analysis (P=0.0441), being also identified as an independent prognostic factor in multivariate analysis (P=0.0451). CONCLUSIONS: The present study supported evidence for possible implication of MSH2, MLH1 and MGMT proteins in the formation and progression of mobile tongue SCC. PMID- 21029182 TI - Association between substandard classroom ventilation rates and students' academic achievement. AB - This study focuses on the relationship between classroom ventilation rates and academic achievement. One hundred elementary schools of two school districts in the southwest United States were included in the study. Ventilation rates were estimated from fifth-grade classrooms (one per school) using CO(2) concentrations measured during occupied school days. In addition, standardized test scores and background data related to students in the classrooms studied were obtained from the districts. Of 100 classrooms, 87 had ventilation rates below recommended guidelines based on ASHRAE Standard 62 as of 2004. There is a linear association between classroom ventilation rates and students' academic achievement within the range of 0.9-7.1 l/s per person. For every unit (1 l/s per person) increase in the ventilation rate within that range, the proportion of students passing standardized test (i.e., scoring satisfactory or above) is expected to increase by 2.9% (95%CI 0.9-4.8%) for math and 2.7% (0.5-4.9%) for reading. The linear relationship observed may level off or change direction with higher ventilation rates, but given the limited number of observations, we were unable to test this hypothesis. A larger sample size is needed for estimating the effect of classroom ventilation rates higher than 7.1 l/s per person on academic achievement. PRACTICAL IMPLICATIONS: The results of this study suggest that increasing the ventilation rates toward recommended guideline ventilation rates in classrooms should translate into improved academic achievement of students. More studies are needed to fully understand the relationships between ventilation rate, other indoor environmental quality parameters, and their effects on students' health and achievement. Achieving the recommended guidelines and pursuing better understanding of the underlying relationships would ultimately support both sustainable and productive school environments for students and personnel. PMID- 21029183 TI - Ultrafine particle concentrations and exposures in seven residences in northern California. AB - Human exposures to ultrafine particles (UFP) are poorly characterized given the potential associated health risks. Residences are important sites of exposure. To characterize residential exposures to UFP in some circumstances and to investigate governing factors, seven single-family houses in California were studied during 2007-2009. During multiday periods, time-resolved particle number concentrations were monitored indoors and outdoors and information was acquired concerning occupancy, source-related activities, and building operation. On average, occupants were home for 70% of their time. The geometric mean time average residential exposure concentration for 21 study subjects was 14,500 particles per cm(3) (GSD = 1.8; arithmetic mean +/- standard deviation = 17,000 +/- 10,300 particles per cm(3)). The average contribution to residential exposures from indoor episodic sources was 150% of the contribution from particles of outdoor origin. Unvented natural-gas pilot lights contributed up to 19% to exposure for the two households where present. Episodic indoor source activities, most notably cooking, caused the highest peak exposures and most of the variation in exposure among houses. Owing to the importance of indoor sources and variations in the infiltration factor, residential exposure to UFP cannot be characterized by ambient measurements alone. PRACTICAL IMPLICATIONS: Indoor and outdoor sources each contribute to residential ultrafine particle (UFP) concentrations and exposures. Under the conditions investigated, peak exposure concentrations indoors were associated with cooking, using candles, or the use of a furnace. Active particle removal systems can mitigate exposure by reducing the persistence of particles indoors. Eliminating the use of unvented gas pilot lights on cooking appliances could also be beneficial. The study results indicate that characterization of human exposure to UFP, an air pollutant of emerging public health concern, cannot be accomplished without a good understanding of conditions inside residences. PMID- 21029184 TI - Ultrafine particle concentrations and exposures in six elementary school classrooms in northern California. AB - Potential health risks may result from environmental exposure to ultrafine particles (UFP), i.e., those smaller than 0.1 MUm in diameter. One important exposure setting that has received relatively little attention is school classrooms. We made time-resolved, continuous measurements of particle number (PN) concentrations for 2-4 school days per site (18 days total) inside and outside of six classrooms in northern California during normal occupancy and use. Additional time-resolved information was gathered on ventilation conditions, occupancy, and classroom activity. Across the six classrooms, average indoor PN concentrations when students were present were 5200-16,500/cm(3) (overall average 10,800/cm(3)); corresponding outdoor concentrations were 9000-26,000/cm(3) (overall average 18,100/cm(3)). Average indoor levels were higher when classrooms were occupied than when they were unoccupied because of higher outdoor concentrations and higher ventilation rates during occupancy. In these classrooms, PN exposures appear to be primarily attributable to outdoor sources. Indoor emission sources (candle use, cooking on an electric griddle, use of a heater, use of terpene-containing cleaning products) were seen to affect indoor PN concentrations only in a few instances. The daily-integrated exposure of students in these six classrooms averaged 52,000/cm(3) h/day for the 18 days monitored. PRACTICAL IMPLICATIONS: This study provides data and insight concerning the UFP exposure levels children may encounter within classrooms and the factors that most significantly affect these levels in an urban area in northern California. This information can serve as a basis to guide further study of children's UFP exposure and the potential associated health risks. PMID- 21029185 TI - Training and playing football in hot environments. PMID- 21029186 TI - Temperature and neuromuscular function. AB - This review focuses on the effects of different environmental temperatures on the neuromuscular system. During short duration exercise, performance improves from 2% to 5% with a 1 degrees C increase in muscle temperature. However, if central temperature increases (i.e., hyperthermia), this positive relation ceases and performance becomes impaired. Performance impairments in both cold and hot environment are related to a modification in neural drive due to protective adaptations, central and peripheral failures. This review highlights, to some extent, the different effects of hot and cold environments on the supraspinal, spinal and peripheral components of the neural drive involved in the up- and down regulation of neuromuscular function and shows that temperature also affects the neural drive transmission to the muscle and the excitation-contraction coupling. PMID- 21029187 TI - Central fatigue and neurotransmitters, can thermoregulation be manipulated? AB - Fatigue is a complex phenomenon that can be evoked by peripheral and central factors. Although it is obvious that fatigue has peripheral causes such as glycogen depletion and cardiovascular strain, recent literature also focuses on the central origin of fatigue. It is clear that different brain neurotransmitters -such as serotonin, dopamine and noradrenaline--are implicated in the occurrence of fatigue, but manipulation of these neurotransmitters produced no conclusive results on performance in normal ambient temperature. Exercise in the heat not only adds an extra challenge to the cardiorespiratory system, but also to the brain. This provides a useful tool to investigate the association between exercise-induced hyperthermia and central fatigue. This review focuses on the effects of pharmacological manipulations on performance and thermoregulation in different ambient temperatures. Dopaminergic reuptake inhibition appears to counteract hyperthermia-induced fatigue in 30 degrees C, while noradrenergic neurotransmission shows negative effects on performance in both normal and high temperature, and serotonergic manipulations did not lead to significant changes in performance. It is, however, unlikely that one neurotransmitter system is responsible for the delay or onset of fatigue. Further research is required to determine the exact mechanisms of fatigue in different environmental conditions. PMID- 21029188 TI - Exercise in a hot environment: the skin circulation. AB - The combined metabolic and thermoregulatory demands of exercise in the heat place an exceptional burden on the circulation, more than can be met through cardiac output and blood flow redistribution. Blood flow to muscle is not reduced by heat stress in exercise and cardiac output is insufficient to meet competing demands from skin and muscle. Skin blood flow during exercise in the heat is limited in several ways. Dynamic exercise causes a cutaneous vasoconstriction at exercise onset through increased vasoconstrictor activity, both in cool and warm conditions. As exercise continues, internal temperature reaches a threshold for increased active vasodilator activity that is elevated by exercise, but reduced by high skin temperature. Beyond that threshold, skin blood flow is limited well below what would be achieved at rest with the same thermal drive through a limit to the active vasodilator system. This combination of restraints on cutaneous vasodilator function compromises temperature regulation. Internal temperature rises to levels that limit exercise through central thermal effects, rather than loss of blood pressure or a reduction in blood flow to active muscle. PMID- 21029189 TI - Dehydration and rehydration in competative sport. AB - Dehydration, if sufficiently severe, impairs both physical and mental performance, and performance decrements are greater in hot environments and in long-lasting exercise. Athletes should begin exercise well hydrated and should drink during exercise to limit water and salt deficits. Many athletes are dehydrated to some degree when they begin exercise. During exercise, most drink less than their sweat losses, some drink too much and a few develop hyponatraemia. Athletes should learn to assess their hydration needs and develop a personalized hydration strategy that takes account of exercise, environment and individual needs. Pre-exercise hydration status can be assessed from urine frequency and volume, with additional information from urine color, specific gravity or osmolality. Changes in hydration status during exercise can be estimated from the change in body mass: sweat rate can be estimated if fluid intake and urinary losses are also measured. Sweat salt losses can be determined by collection and analysis of sweat samples. An appropriate, individualized drinking strategy will take account of pre-exercise hydration status and of fluid, electrolyte and substrate needs before, during and after a period of exercise. PMID- 21029190 TI - Hemorheology and exercise: effects of warm environments and potential consequences for sickle cell trait carriers. AB - The relationship between blood rheology and hemodynamics is complex, and the following review presents several aspects of exercise hemorheology, with the focus on both cycling and running as exercise. The scientific literature assessing the effects of warm environment on exercise hemorheology is presented and the potential consequences for a specific population, sickle cell trait carriers, are discussed. PMID- 21029191 TI - Interconnections between thermal perception and exercise capacity in the heat. AB - Some models of exercise regulation suggest that exercise performance, rather than being solely limited by the attainment of fatigue in one or more physiological systems, is modulated by psychological factors. Extrapolating from such models, exercise capacity and voluntary performance during exercise in hot environments may be governed by a complex interplay between the physiological effects of hyperthermia along with psychological input stemming from the conscious perception of the thermal environment. Evidence is emerging for a neuroanatomical basis for peripheral and central thermal receptors to elicit both a distinct physiological response such as shivering or sweating along with being mapped into an overall subjective sensation of homeostasis. Experimental evidence supporting this interactivity includes the demonstration that physiological manipulations, such as an increased fitness, appear to confer an attenuation of thermal discomfort during whole-body exercise despite similar levels of physiological strain. At the same time, psychological interventions have proven effective in decreasing perceived thermal strain and extending exercise performance in hot environments. The purpose of this review was to survey the potential interactions between thermal perception and exercise performance in the heat. PMID- 21029192 TI - Cognitive function in hot environments: a question of methodology. AB - The physiological responses of thermal stress and its consequences on health have been well documented. However, the effect on cognitive function remains equivocal despite a substantial number of studies conducted in the area. Methodological discrepancies across different studies have made it difficult to conclude whether or not heat exposure per se has an adverse effect upon cognitive function and under what specific environmental and physiological conditions these alterations appear. This article gives an overview of the different confounding factors that have made it difficult to make conclusive interpretations. In addition, the current state of knowledge is presented and discussed with reference to the Global Workspace theory. Although previously presented conclusions are promising, much remains to be completed before understanding the mechanisms that could explain the relationship between heat exposure and cognitive function. Finally, recommendations are presented for further research in this area. PMID- 21029193 TI - Cycling in the heat: performance perspectives and cerebral challenges. AB - Cycling performances require periods with high power output and consequently large endogenous heat production. During cycling in temperate or cold climates, heat is mainly released from the skin to the surroundings via convection, whereas evaporative heat loss becomes the dominant or only mechanism for heat dissipation when the environmental temperature increases. Accordingly, large sweat rates are required, which may challenge the cyclists' electrolyte and water balance. Furthermore, the cooling capacity of the environment may become a limiting factor for the ability to maintain heat balance, for example during cycling in very humid climates or when cycling up-hill as the wind speed decreases and reduces the maximal rate of evaporative heat loss. Hyperthermia may in itself hamper performance, but especially in combination with dehydration it may deteriorate the cyclist's ability to maintain power output. Fatigue mechanisms involve cardiovascular stressing, but it also appears that factors within the central nervous system are of major importance for motor performance during such exercise. However, the influence of the environmental temperature on cycling performance appears to vary markedly depending on the course, the air humidity and the cyclist ability to avoid dehydration. If hyperthermia becomes a major issue, it will deteriorate performance, but as long as temperature and water balance can be established, the high air temperature may actually benefit performance because air density and air resistance will decrease and lower the power output required to maintain a given velocity. PMID- 21029194 TI - Different effects of heat exposure upon exercise performance in the morning and afternoon. AB - Independent of environmental conditions, rectal temperature follows a circadian rhythm with an acrophase in the late afternoon. In neutral environment, this diurnal increase in temperature is believed to have a passive warm-up effect improving muscle contractility, and in turn, muscle force, power and performance. However, a hot environment blunts the diurnal variation in muscle function by only improving muscle contractility, and in turn, muscle force, power and performance in the morning, when body temperature is at its lowest. Despite this diurnal variation in muscle function, long-duration exercise is only slightly affected by the time-of-day in neutral environment. However, higher afternoon body temperatures can reduce the heat storage capacity and result in a reduction in exercise capacity in hot environments. In addition, in parallel to the circadian variations in muscle contractility and central temperature, exercise capacity in hot environment may also be affected by the diurnal variations in melatonin concentration and in the onset of peripheral vasodilatation and sweating. PMID- 21029195 TI - Hydration: special issues for playing football in warm and hot environments. AB - The high metabolic rates and body temperatures sustained by football players during training and matches causes sweating--particularly when in warm or hot environments. There is limited published data on the effects of this sweat loss on football performance. The limited information available, together with knowledge of the effects of sweat loss in other sports with skill components as well as endurance and sprint components, suggests that the effects of sweating will be similar as in these other activities. Therefore, the generalization that, on average, a body mass reduction equivalent to 2% should be the acceptable limit of sweat losses seems reasonable. This magnitude and more, of sweat loss is a common occurrence for some players. Sodium is the main electrolyte lost in sweat but there is large variability in sodium losses between players. However, the extent of sodium losses in some players may be such that its replacement is warranted for these players. Although football is a team sport, the great individual variability in sweat and electrolyte losses of players in the same training session or match dictates that individual monitoring to determine individual water and electrolyte requirements should be an essential part of a player's nutrition strategy. PMID- 21029196 TI - Distance running in hot environments: a thermal challenge to the elite runner. AB - Endurance performance is impaired in the heat, and a combination of high temperature and high humidity presents a major challenge to the elite marathon runner, who must sustain a high metabolic rate throughout the race. The optimum temperature for marathon performance is generally about 10-12 degrees C. The optimum temperature may be lower for faster runners than for slower runners. Sweat evaporation limits the rise in core temperature, but dehydration will impair cardiovascular function, leading to a fall in blood flow to muscle, skin and other tissues. There is growing evidence that the effects of high ambient temperature and dehydration on performance of exercise may be mediated by effects on the central nervous system. This seems to involve serotonergic and dopaminergic functions. PMID- 21029197 TI - Physiological strain and countermeasures with firefighting. AB - Protective clothing is integral to the task of firefighting, but at the same time can increase physiological strain and impair work capacity. Encapsulation of the head and the high thermal resistance and/or low water vapor permeability of the clothing ensemble impede evaporative heat dissipation, thus elevating the rate of heat storage and creating a state of uncompensable heat stress (UHS). In addition, the additional weight from carrying a supplemental air supply and the greater respiratory work of breathing through a regulator can create a negative spiral of thermal hyperpnea from greater respiratory demands and metabolic heat production. The elevated respiratory demands also increase cardiac strain and potentially the risk for myocardial events. Tolerance time during UHS is determined by three factors: the core temperature at the beginning of the heat stress exposure, the core temperature that can be tolerated before exhaustion or collapse ensues, and the rate of increase in core temperature from the beginning to end of the heat stress exposure. Protective clothing is often employed in highly dynamic environments, making portability, longevity and integration with the task requirements and clothing critical design characteristics for countermeasures. To date, most countermeasures have been relatively indirect in nature, primarily with alterations in work scheduling along with physiological manipulations such as cooling manipulations during recovery periods. Advances are required in materials science to develop lighter and less restrictive protective equipment, concurrent with cooling strategies that target specific regions or which can be effectively implemented during exercise. PMID- 21029198 TI - Living, training and playing in the heat: challenges to the football player and strategies for coping with environmental extremes. AB - Dehydration and hyperthermia both, if sufficiently severe, will impair exercise performance. Dehydration can also impair performance of tasks requiring cognition and skill. Body temperature may exceed 40 degrees C in competitive games played in hot weather, but limited data are available. Football played in the heat, therefore, poses a challenge, and effects on some aspects of performance become apparent as environmental temperature increases above about 12-15 degrees C. Prior acclimatization will reduce the impact of high environmental temperatures but provides limited protection when humidity is also high. Ingestion of fluids is effective in limiting the detrimental effects on performance: drinks with added carbohydrate and electrolytes are generally more effective than plain water and drinks may be more effective if taken cold than if taken at ambient temperature. Pre-exercise lowering of body temperature may aid some aspects of performance, but the efficacy has not been demonstrated in football. PMID- 21029199 TI - Examination of fatigue development in elite soccer in a hot environment: a multi experimental approach. AB - The study examines fatigue in elite soccer played in hot conditions. High-profile soccer players (n=20) were studied during match play at ~31 degrees C. Repeated sprint and jump performances were assessed in rested state and after a game and activity profile was examined. Additionally, heart rate (HR), blood lactate, muscle temperature and body mass changes were determined. Repeated sprint and jump performances were reduced (P<0.05) by 2.6% and 8.2%, respectively, after the game. The fatigue index in the repeated sprint test was 6.0+/-0.7% after the game compared with 1.7+/-1.0% at rest (P<0.05). High-intensity running was 57+/-4% lower (P<0.05) during the last 15-min interval of the game compared with the first 15-min period. No differences were observed in mean HR or blood lactates between halves. Muscle temperature was 40.5+/-0.4 degrees C after the first half, which was 0.8+/-0.2 degrees C higher (P<0.05) than after the second half. Net fluid loss during the game was >2% of the body mass. Correlations were observed between net-fluid loss and repeated sprint test fatigue index after the game (r=0.73, P<0.05) and Yo-Yo intermittent recovery, level 1 test performance and high-intensity running during the final 15 min of the game (r=0.51, P<0.05). The study provides direct evidence of compromised repeated sprint and jump performances induced by soccer match play and pronounced reduction in high intensity running toward the end of an elite game played in a hot environment. This fatigue could be associated training status and hyperthermia/dehydration. PMID- 21029200 TI - Hydration and sweating responses to hot-weather football competition. AB - During a football match played in warm (34.3 +/- 0.6 degrees C), humid (64 +/- 2% rh) conditions, 22 male players had their pre-match hydration status, body mass change, sweat loss and drinking behavior assessed. Pre-match urine specific gravity (1.012 +/- 0.006) suggested that all but three players commenced the match euhydrated. Players lost 3.1 +/- 0.6 L of sweat and 45 +/- 9 mmol of sodium during the 90-min match and replaced 55 +/- 19% of their sweat losses and hence by the end of the game were 2.2 +/- 0.9% lighter. The water volume consumed during the game was highly variable (1653 +/- 487 mL; 741-2387 mL) but there was a stronger relationship between the estimated pre-game hydration status and water volume consumed, than between sweat rate and water volume consumed. In a second match, with the same players 2 weeks later in 34.4 +/- 0.6 degrees C, 65 +/- 3% rh, 11 players had a sports drink available to them before and during the match in addition to water. Total drink volume consumed during the match was the same, but approximately half the volume was consumed as sports drink. The results indicate that substantial sweat water and electrolyte losses can occur during match play in hot conditions and a substantial water and sodium deficit can occur in many players even when water or sports drink is freely available. PMID- 21029201 TI - Effect of hot environmental conditions on physical activity patterns and temperature response of football players. AB - Heat stress may contribute to decreased match performance when football is played in extreme heat. This study evaluated activity patterns and thermal responses of players during soccer matches played in different environmental conditions. Non acclimatized soccer players (n=11, 20+/-2 years) played two matches in conditions of moderate heat (MH) and high heat (HH) index. Core temperature (T(c) ) and physical performance were measured using a telemetric sensor and a global positioning system, respectively. The average ambient temperature and relative humidity were MH 34+/-1 degrees C and 38+/-2%; HH 36+/-0 degrees C and 61+/-1%. Peak T(c) in the MH match was 39.1+/-0.4 degrees C and in the HH match it was 39.6+/-0.3 degrees C. The total distance covered in the first and second halves was 4386+/-367 and 4227+/-292 m for the MH match and 4301+/-487 and 3761+/-358 m for the HH match. Players covered more distance (P<0.001) in the first half of the HH match than in the second half. In football matches played at high environmental temperature and humidity, the physical performance of the players may decrease due to high thermal stress. PMID- 21029202 TI - The effects of exercise, heat, cooling and rehydration strategies on cognitive function in football players. AB - We investigated the cognitive effects of exercising in the heat on the field players of two football teams in a series of three matches. Different rehydration and cooling strategies were used for one of the teams during the last two games. Cognitive functions were measured before, during and immediately after each football match, as well as core temperature, body mass, plasma osmolality and glucose levels, allowing an estimate of their differential impacts on cognition. The pattern of results suggests that mild-moderate dehydration during exercise in the heat (up to 2.5%) has no clear effect on cognitive function. Instead, plasma glucose and core temperature changes appear to be the main determinants: higher glucose was related to faster and less accurate performance, whereas core temperature rises had the opposite effect. The 50% correlation between plasma glucose and core temperatures observed during exercise in the heat may help to stabilize cognitive performance via their opposing effects. The glucose-like effects of sports drinks appear to be mediated by increased plasma glucose levels, because drinks effects became non-significant when plasma glucose levels were added to the models. The cooling intervention had only a beneficial effect on complex visuo-motor speed. PMID- 21029203 TI - Current knowledge on playing football in hot environments. PMID- 21029204 TI - Semantic dementia with lower motor neuron disease showing FTLD-TDP type 3 pathology (sensu Mackenzie). AB - We describe a case of frontotemporal lobar degeneration with semantic dementia and lower motor neuron disease. A 63-year-old man presented with the full clinical picture of semantic dementia, including semantic anomia, surface alexia, lexical agraphia, associative agnosia, prosopagnosia and phonagnosia. Flaccid dysarthria, bulbar dysphagia and fasciculations developed 7 years after onset, followed by death within a year. The neuropathological examination showed heavy neuronal loss in the anterior temporal lobe cortex, dorsal vagal and hypoglossal nuclei and anterior horns of the spinal cord. Ubiquitin- and TDP-43-positive cytoplasmic inclusions were abundant in layer II of affected cortices and in granular cells of the hippocampal dentate gyrus, whereas dystrophic neurites were sparse and intranuclear inclusions absent. It is concluded that FTLD-TDP type 3 can be associated with semantic dementia and lower motor neuron disease in combination. PMID- 21029205 TI - Expert opinion: efficacy of superficial chemical peels in active acne management- what can we learn from the literature today? Evidence-based recommendations. AB - BACKGROUND: Superficial chemical peels offer therapeutic results in a convenient, affordable treatment. Many clinicians use these peels in the treatment of acne and acne-prone oily skin. OBJECTIVES: This article examines the evidence base that supports the widespread use of superficial peels in this setting. METHODS: A search of the English language medical literature was performed to identify clinical trials that formally evaluated the use of chemical peeling in active acne. RESULTS: Search of the literature revealed very few clinical trials of peels in acne (N=13); a majority of these trials included small numbers of patients, were not controlled and were open label. The evidence that is available does support the use of chemical peels in acne as all trials had generally favourable results despite differences in assessments, treatment regimens and patient populations. Notably, no studies of chemical peels have used an acne medication as a comparator. As not every publication specified whether or not concomitant acne medications were allowed, it is hard to evaluate clearly how many of the studies evaluated the effect of peeling alone. This may be appropriate, however, given that few clinicians would use superficial chemical peels as the sole treatment for acne except in rare instances where a patient could not tolerate other treatment modalities. CONCLUSIONS: In the future, further study is needed to determine the best use of chemical peels in this indication. PMID- 21029206 TI - Acne fulminans: explosive systemic form of acne. AB - Acne fulminans (AF) is a rare severe form of acne vulgaris associated with systemic symptoms. It primarily affects male adolescents. Although the aetiology of AF remains unknown, many theories have been advanced to explain it. There have been reported associations with increased androgens, autoimmune complex disease and genetic pre-disposition. The disease is destructive, with the acute onset of painful, ulcerative nodules on the face, chest and back. The associated systemic manifestations such as fever, weight loss and musculoskeletal pain are usually present at the onset. The patients are febrile, with leucocytosis and an increased erythrocyte sedimentation rate. They may require several weeks of hospitalization. The treatment of AF has been challenging; the response to traditional acne therapies is poor. The recommended treatment is aggressive and consists of a combination of oral steroids and isotretinoin. To avoid the relapses, duration of such treatment should not be less than 3-5 months. Although the prognosis for patients treated appropriately is good, these acute inflammatory nodules often heal with residual scarring. PMID- 21029207 TI - Metabolic syndrome in Tunisian psoriatic patients: prevalence and determinants. AB - BACKGROUND: A significant association between psoriasis and the metabolic syndrome (MetS) has been frequently reported. OBJECTIVE: The aim of this study was to specify the main factors that determine the MetS in psoriatic Tunisian patients. METHODS: A case-control study has included 164 psoriatic patients and 216 controls. RESULTS: The prevalence of MetS was higher in cases than in controls but without statistical differences [35.5% vs. 30.8%, odds ratio (OR): 1.39 CI: 0.88-2.18; P=0.095]. According to gender, the prevalence of MetS was significantly increased only in psoriatic women (47.4% vs. 30%, OR: 1.89, CI: 1.11-3.21; P=0.01). A multiple logistic regression, considering the effect of age, and gender, showed that the prevalence of MetS was significantly higher in cases than in controls (OR: 1.73, CI: 1.06-2.82; P=0.03). MetS components analysed seperately showed a significantly higher prevalence of decreased high density lipoprotein cholesterol (HDLc) (60.9% vs. 35.9%, OR: 2.77, CI: 1.8-4.27, P<0.001) and for increased hypertension (50% vs. 40%, OR: 1.48, CI: 0.97-2.257, P=0.04) in psoriatic patients. According to gender, HDLc was significantly decreased in both genders (male: OR: 2.075, CI: 1.24-3.47, P=0.004; female: OR: 3.58, CI: 2.07-6.19, P<0.0001), while hypertension was increased only in psoriatic men (OR: 2.09, CI: 1.24-3.51, P=0.004) and abdominal obesity only in psoriatic women (OR: 2.31, CI: 1.30-4.11, P=0.002). CONCLUSION: Decreased HDLc is the main biological abnormality that characterized MetS in Tunisian psoriatic patients. Moreover, contrary to men, psoriatic women have shown a significantly higher prevalence of MetS, which is, in addition to decreased HDLc, mainly attributed to abdominal obesity. PMID- 21029208 TI - A first prospective randomized controlled trial on the efficacy and safety of synchronous balneophototherapy vs. narrow-band UVB monotherapy for atopic dermatitis. AB - BACKGROUND: Data from an uncontrolled trial suggest synchronous balneophototherapy (sBPT), which simulates treatment conditions at the Dead Sea, to be effective in the management of atopic dermatitis (AD). OBJECTIVES: The purpose of this prospective randomized controlled study was to compare the efficacy and safety of sBPT with narrow-band (NB) UVB monotherapy (PT) for AD. METHODS: In this phase III multicentre trial, 180 patients with moderate-to severe AD were allocated to two groups in a 1:1 ratio; group 1 received sBPT consisting of NB UVB treatment and synchronous bathing in 10% Dead Sea salt solution, group 2 monotherapy with UVB 311 nm. The confirmatory study design consisted of up to 35 treatment sessions. Primary endpoint, analysed on an intention-to-treat-basis (n=169), was the relative improvement of the severity SCORing of the Atopic Dermatitis Index (SCORAD) from baseline to the end of treatment (35 sessions or early cure). Sample-size calculation aimed at establishing at least 15% superiority. RESULTS: SCORing of the Atopic Dermatitis Index at baseline was comparable between sBPT (61.8+/-14.1) and PT (61.5+/-12.4) group. At the end of therapy, a clinically relevant and statistically significant difference of 26.2% could be shown (P<0.001). Exploratory testing showed statistically significant superiority of sBPT after 6 months. Mild adverse events more frequently occurred in the sBPT group (n=46, PT: n=31), whereas more patients withdrew early because of adverse events in the PT group (n=6, sBPT: n=2). CONCLUSIONS: A clear advantage of sBPT in comparison to PT was proven. Tolerability was comparable; both treatments showed to be safe. PMID- 21029209 TI - Spectrum of autoantibodies other than anti-desmoglein in pemphigus patients. AB - BACKGROUND: Pemphigus is a life-threatening autoimmune blistering disease mediated by autoantibodies against adhesion molecule of the skin. Its concurrence with systemic and organ-specific autoimmune disease was described in case reports. OBJECTIVES: To evaluate the presence of a broad spectrum of organ specific and non-organ-specific autoantibodies other than anti-desmoglein antibodies in pemphigus patients. PATIENTS AND METHODS: Serum samples were obtained from 105 pemphigus foliaceus (PF) patients, 51 pemphigus vulgaris (PV) patients and 50 controls. Both indirect immunofluorescence assay and ELISA were used to assess the presence of autoantibodies related to connective tissue diseases, autoimmune hepatitis, vasculitis, rheumatoid arthritis, coeliac disease, diabetes and thyroiditis. RESULTS: Significant difference was observed between the three groups for anti-thyroglobulin antibodies in the pemphigus foliaceus group (18% vs. 4%, P=0.03). A significantly higher occurrence of IgM anti-cardiolipin (P=0.03), IgG anti-reticulin (P=0.01) and IgG anti-gliadin antibodies (P=0.008) were observed in the PV group. Cases with more than four autoantibodies were frequently positives for both anti-desmoglein 1 and anti desmoglein 3. CONCLUSION: Autoantibodies other than anti-desmoglein antibodies are not rare in pemphigus patients. Clinical and serological follow-up of pemphigus patients with positive autoantibodies are needed to clarify their impact in disease evolution. PMID- 21029210 TI - Pemphigus vulgaris and season: are they really related or not? PMID- 21029211 TI - Driving improvements in nutritional care. PMID- 21029212 TI - Qualitative research in nutrition and dietetics: getting started. AB - Qualitative research is well placed to answer complex questions about food related behaviour because it investigates how and why individuals act in certain ways. The field of qualitative health research is undoubtedly gaining momentum and, increasingly, there is a recognition that it should be a vital part of the decision-making processes that direct the development of health policy and practice. Much of the guidance available, however, is difficult to navigate for those new to 'qualitative research', and there is little discussion of qualitative research issues specifically in relation to nutrition and dietetics. This review, the first in a series, outlines the field of qualitative enquiry, its potential usefulness in nutrition and dietetics, and how to embark upon this type of research. Furthermore, it describes a process to guide high-quality qualitative research in this area that proceeds from the research question(s) and considers the key philosophical assumptions about ontology, epistemology and methodology that underpin the overall design of a study. Other reviews in this series provide an overview of the principal techniques of data collection and sampling, data analysis, and quality assessment of qualitative work, and provide some practical advice relevant to nutrition and dietetics, along with glossaries of key terms. PMID- 21029215 TI - Healthy midlife Canadian women: how bone health is considered in their food choice systems. AB - BACKGROUND: The incidence of osteoporosis is predicted to increase as Western populations age. Diet is considered to be an important modifiable factor in bone health, yet the diets of many women are insufficient in calcium and vitamin D, which comprise two key nutrients for bone health. This focus group study explored ways in which midlife women consider bone health in their personal food choice systems. METHODS: Data were obtained in six audio-recorded focus groups from a total of 36 women from upper, middle and lower income neighbourhoods. Open and axial coding and thematic analysis revealed shared and unique themes across and within the income groups. Use of member checks, peer debriefing, and independent and team data analysis enhanced rigour in the findings. RESULTS: All participants were aware of osteoporosis. Most women idealised making simple food decisions and eating for 'holistic' health, but not specifically for bone health. Most midlife women were not motivated to change their diets, few had deliberately increased their intake of calcium and vitamin D through foods and supplements, and few others had simplified their food decisions. CONCLUSIONS: Midlife women in the present study did not make eating for bone health a priority in their food choice systems. Instead, women wanted to eat for 'holistic' health, and only by implication bone health. PMID- 21029216 TI - Characterisation of arcuate nucleus kisspeptin/neurokinin B neuronal projections and regulation during lactation in the rat. AB - Lactation results in negative energy balance in the rat leading to decreased gonadotrophin-releasing hormone (GnRH) release and anoestrus. Inhibited GnRH release may be a result of decreased stimulatory tone from neuropeptides critical for GnRH neuronal activity, such as kisspeptin (Kiss1) and neurokinin B (NKB). The present study aimed to identify neuronal projections from the colocalised population of Kiss1/NKB cells in the arcuate nucleus (ARH) using double-label immunohistochemistry to determine where this population may directly regulate GnRH neuronal activity. Additionally, the present study further examined lactation-induced changes in the Kiss1 system that could play a role in decreased GnRH release. The colocalised ARH Kiss1/NKB fibres projected primarily to the internal zone of the median eminence (ME) where they were in close proximity to GnRH fibres; however, few Kiss1/NKB fibres from the ARH were seen at the level of GnRH neurones in the preoptic area (POA). Arcuate Kiss1/NKB peptide levels were decreased during lactation consistent with previous mRNA data. Surprisingly, anteroventral periventricular (AVPV) Kiss1 peptide levels were increased, whereas Kiss1 mRNA levels were decreased during lactation, suggesting active inhibition of peptide release. These findings indicate ARH Kiss1/NKB and AVPV Kiss1 appear to be inhibited during lactation, which may contribute to decreased GnRH release and subsequent reproductive dysfunction. Furthermore, the absence of a strong ARH Kiss1/NKB projection to the POA suggests regulation of GnRH by this population occurs primarily at the ME level via local projections. PMID- 21029217 TI - Effects of RFamide-related peptide (RFRP)-1 and RFRP-3 on oxytocin release and anxiety-related behaviour in rats. AB - RFamide-related peptides (RFRP-1 and RFRP-3) are localised in neurones of the dorsomedial hypothalamus in rats. The dorsomedial hypothalamus plays an essential role in neuroendocrine and behavioural stress responses. In the present study, we examined the role of RFRP in the control of neuroendocrine and behavioural responses in rats. Stressful stimuli increased expression of Fos protein in RFRP immunoreactive neurones of the dorsomedial hypothalamus, suggesting that stressful stimuli activate RFRP neurones. Intracerebroventricular injection of RFRPs increased the expression of Fos protein in oxytocin neurones in the hypothalamus and plasma concentrations of adrenocorticotrophic hormone and oxytocin. The hypothalamic paraventricular and supraoptic nuclei expressed mRNA of GPR147, the putative RFRP receptor, and application of RFRPs to isolated supraoptic nuclei facilitated oxytocin release, suggesting that RFRPs activate oxytocin neurones directly. Furthermore, the administration of RFRPs induced anxiety-related behaviour in rats in open-field tests. All these data taken together suggest that RFRPs play a role in the control of neuroendocrine and behavioural stress responses in rats. PMID- 21029219 TI - Safe blood transfusion practices in blood banks of Karachi, Pakistan. AB - BACKGROUND: Since 1997, legislations pertaining to safe blood transfusion (SBT) have evolved considerably in Pakistan. The objective of this study was to evaluate the SBT practices in the blood banks of Pakistan. METHODS: Twenty-three blood banks were randomly selected from a list of registered 40 in Karachi, the largest city in Pakistan. To evaluate the SBT practices in the selected blood banks, a questionnaire and a checklist were administered during 2007-2008. RESULTS: Of the 23 blood banks surveyed, 4 (17%) were affiliated with government or a semi-government institution; 16 (70%) blood banks had a healthy donor recruitment program and 2 (9%) of the blood banks agreed that they recruited remunerated (paid) blood donors. Donors were screened for HIV, Hepatitis B, Hepatitis C and syphilis by all 23 blood banks, whereas malaria was screened by all blood banks but one. CONCLUSION: SBT practices in Karachi have improved since 1995; an active role by the government in policy-making has proven effective. PMID- 21029218 TI - KRAS and BRAF mutation analysis can be reliably performed on aspirated cytological specimens of metastatic colorectal carcinoma. AB - BACKGROUND: Sanger sequencing is one of several reliable methods in use to detect KRAS and BRAF mutations to facilitate clinical patient selection for anti epidermal growth factor receptor (EGFR) monoclonal antibody therapy in unresectable metastatic colorectal adenocarcinoma (CRC). Most analyses are made on pretreatment biopsy or resection specimens. There is a scarcity of published studies on the suitability of cytological samples for KRAS testing in this setting. METHODS: DNA extraction was attempted on 11 search-retrieved paired cases of histological resections or excisions of CRC and their corresponding cytological samples (representing metastases) and tested for KRAS mutations in exon 2 and 3, as well as BRAF exon 15 mutations by Sanger sequencing. Only KRAS wild-type cases were subjected to BRAF analysis because this is the setting with true diagnostic value, as these mutations are mutually exclusive. RESULTS: Of the 11 paired cases analysed, only eight histology cases showed satisfactory DNA quality for sequencing. Thus, only eight of the corresponding cytology cases were analysed. Seven of the eight cases tested showed the same KRAS genotype on both the aspirated cytology specimen of metastatic carcinoma and the primary tumour (histological specimen), from which we derive an overall concordance rate of 87.5%. The single discordant case was likely to be a true difference as it was demonstrated again on repeat testing of both samples. No BRAF mutations were detected on the four KRAS wild-type cases. CONCLUSION: A range of cytological samples are suitable for KRAS and BRAF mutation testing, be it from previously stained preparations or cell blocks. These samples would be highly valuable in cases where cytological samples are the only material available for mutation testing. PMID- 21029220 TI - Perceptions of terminally ill patients and family members regarding home and hospice as places of care at the end of life. AB - To enable demand-based palliative care, it is important to know the perceptions of terminally ill patients and their family members regarding home and hospice as places of care at the end of life. Eight women and five men suffering from cancer and with a life expectancy of 3 months or less were interviewed. In each case one of the family members was also interviewed. Four patients spent their last phase of life at home, nine in a hospice. This paper provides further insight in the patient perspective in palliative care. The results reveal that a cohabiting partner seems an important prerequisite for terminally ill patients to stay at home. For spouses it is an obvious choice to facilitate the patients' stay at home, even when it becomes too demanding, something not discussed between spouse and patient. When sufficient care at home seems impossible and the negotiation between patients and family members results in the opinion that living at home is no longer an option, it is decided that the patient moves to a hospice. The choice for the specific setting of the patients' new residence seems to be random; one possibility is pointed out to them and seems appropriate. PMID- 21029221 TI - Issues for researchers to consider when using health-related quality of life outcomes in cancer research. AB - Maintaining quality of life for patients with cancer is a key factor when developing services related to diagnosis, treatment, recovery and/or terminal care. This paper questions whether health-related quality of life (HRQoL) is an appropriate measure of quality of life given that it does not assess factors reported by patients as being most influential, e.g. contact with family and social/cultural interaction. Ambiguity related to the definition and understanding of anxiety, depression and distress as outcomes commonly used by clinicians and researchers when measuring HRQoL in cancer research is also addressed by this paper. The findings of many cancer studies are interpreted and presented on very broad and poorly defined concepts thus preventing the development of a coherent and true understanding of how these outcomes influence quality of life for cancer patients. The authors of this paper conclude that the documentation and clear explanation of the concepts underpinning the choice of instrument and study design is essential but also the inclusion of outcomes related to social support and interaction would provide a more accurate account of quality of life issues in cancer research. PMID- 21029222 TI - A prospective observational study of anaemia management in cancer patients - results from the German Cancer Anaemia Registry. AB - The use of erythropoiesis-stimulating agents (ESA) in cancer patients is still under debate. However, little is known about rationales, strategies, objectives, and effectiveness of anaemia treatments in common practice. The Cancer Anaemia Registry prospectively surveyed about 2000 cancer patients with anaemia throughout Germany. The main objectives of anaemia treatment regardless of modality were to improve quality of life (QOL) and to correct haemoglobin (Hb) levels. The Hb threshold for any anaemia treatment (means +/- SD: 9.4 +/- 1.2 g/dL) but not for blood transfusions (8.7 +/- 1.0 g/dL) depended on cancer type and treatment strategy. Physicians preferred ESA as first-line treatment to prevent transfusions in patients with solid tumours, if they thought that chemotherapy caused the anaemia. If they suspected other causes or patients had lymphoproliferative malignancies, physicians preferred transfusions or attempted to correct underlying disorders; both mainly to improve QOL or prognosis. Effectiveness of all strategies was comparable. However, ESA most effectively prevented transfusions; primary transfusions appeared less suitable for correcting Hb or improving QOL. Using supportive treatments for QOL improvement was common whereas diagnostic measures and intravenous iron therapy were underused. Prospective clinical trials using QOL as end point and evaluating diagnostics in cancer-associated anaemia are warranted. PMID- 21029224 TI - Couples' thoughts about and expectations of their future life after the patient's hospital discharge following acute myocardial infarction. AB - AIM: To describe and interpret couples' thoughts and expectations about their future life after the patient's discharge following acute myocardial infarction. BACKGROUND: An acute myocardial infarction is a challenge for both the patient and his/her partner, as it can disrupt family functioning and dynamics. Earlier research has generally focused on either the patient or the partner, and few studies have explored the experiences of the couple. DESIGN: Qualitative descriptive and interpretative. METHODS: Fifteen couples took part in individual interviews, 4-8 weeks after discharge. Data were analysed in two phases using qualitative content analysis. RESULTS: The first phase of the analysis revealed two categories: 'an active approach to the future' and 'a wait-and-see approach to the future', both of which described the participants' thoughts about the future. In the second phase, the couples' stories were interpreted and grouped into four positions: 'the life companions', 'the tightrope walkers', 'the pathfinders' and 'the observers', which illustrated their visions of the future. CONCLUSIONS: Our results reveal differences in the couples' thoughts about and expectations of their future life, most of them managed the situation by having a positive attitude to life and their future. The couples discovered their resources and compensated for or balanced each other in the early recovery period. RELEVANCE TO CLINICAL PRACTICE: The results indicate the importance of giving both partners the opportunity to express their views of the situation, as this increases nurses' understanding of the impact of the illness on their life and relationship. However, the results also highlight the significance of seeing the couple and showing them consideration both as individuals and as a unit. PMID- 21029223 TI - Disclosing information about randomised controlled trials in oncology: training concept and evaluation of an individualised communication skills training for physicians COM-ON-rct. AB - When physicians disclose information about randomised controlled trials, they have to balance the requirements of conducting high standard research and the respect for patients' rights. Physicians need training in this difficult matter. An individualised communication skills training (CST) about randomised controlled trials for oncologists has been developed. The aim of this publication is to describe the concept of our CST and present data of evaluation by the participants: First, a theoretical introduction about a communication model and important ethical and legal issues was presented. Individual learning goals of participants were then derived through video assessment with actor-patients. The learning goals were the basis for practicing in role play. Individual coaching helped physicians to transfer the made experience into their daily work. Forty physicians have been trained. The acceptance of the training concept was assessed by a questionnaire consisting of 14 items and using a 6-point scale from 1 (very best) to 6 (very bad): the individualised CST was highly accepted (mean = 1.33). Practicing with actor-patients (mean = 1.4), providing constructive feedback (mean = 1.3) and assessing individual learning goals (mean = 1.85) were seen as helpful. Our CST trains physicians to realise best research standards and incorporate patients' rights. PMID- 21029225 TI - Level of psychological distress and social support among patients with limb fractures in Hong Kong. AB - AIMS: To explore the relationship between psychological distress and social support and examine its association with various socio-demographic and clinical characteristics. BACKGROUND: Psychological distress is a common experience in patients after limb fractures. In this regard, a lower level of psychological distress is associated with better social support among patients with various types of diseases. However, there is a paucity of studies examining the relationship between social support and psychological distress among patients with limb fractures. More so, no such study has been conducted in the Chinese population. DESIGN: A cross-sectional and correlational design. METHOD: A convenience sample of participants with upper limb fractures (n = 43) or lower limb fractures (n = 43) was recruited from two orthopaedic wards of a regional acute public hospital in Hong Kong. Data were obtained through face-to-face interview. The Impact of Event Scale was used to measure the level of psychological distress, while the Social Support Questionnaire Short-Form (SSQ6) was used to measure social support. RESULTS: Approximately two-thirds of the participants (n = 54) suffered from medium to high level of psychological distress. Majority of them were fairly satisfied with their social support, with their children being the most common support persons. Furthermore, there was no significant difference in the level of distress between the participants with lower or upper limb fractures. No significant correlation was found between psychological distress and social support. Those who were women, had lower education level and lower monthly income were significantly associated with a higher level of psychological distress. RELEVANCE TO CLINICAL PRACTICE: Patients with fractured limb suffered from a high level of psychological distress. Therefore, a comprehensive assessment of psychological distress should be incorporated as routine assessment. Also, assessing the socio-demographic characteristics of patients should enable nurses to identify patients at risk of developing a high level of psychological distress. PMID- 21029226 TI - Flexible family visitation in the intensive care unit: nurses' decision-making. AB - AIMS AND OBJECTIVES: To identify and explore general strategies used by Danish intensive care unit nurses in everyday decision-making about family visitation. BACKGROUND: In the intensive care unit, relatives experience a strong commitment to watch over and protect the patient. Relatives can provide important help and support to their loved one. To do so, relatives need to be able to stay, preferably at the bedside. Managing a flexible visitation policy, nurses play an important role as gate-keepers at the bedside requiring strong discretionary power. Little is known about the rationale for nurses' decision making when allowing family members to stay by the patient's bedside or asking them to leave the unit. DESIGN: Explorative qualitative interview study. METHOD: In 2005 and 2008, we conducted a grounded theory study based on 11 semi-structured interviews with intensive care unit nurses. RESULTS: In the constantly shifting social context of the intensive care unit, nurses practiced clinical leadership balancing the needs of all parties involved, being mindful that the patient is their primary concern. To do so, they used three general strategies: Clarifying relations, Defining the situation and Guiding relatives in a concurrent and ongoing process, assessing when visiting is appropriate on a minute-to-minute basis. CONCLUSION: The study identifies and describes important professional considerations and values embedded in the nurses' decision making about visitation. Detailed knowledge in this area will provide a concrete basis for internal discussion on specific everyday interactions with visiting relatives, as well as more general discussions on the possibilities for and implications of enhancing flexible family visitation. RELEVANCE TO CLINICAL PRACTICE: To practice a contemporary visitation policy, the complexity of the task, the shifting context of the intensive care unit, the physical surroundings as well as possible limitations given by the staffing level should be acknowledged. The training of intensive care unit nurses should support adaptation to the clinical leadership role. PMID- 21029227 TI - What accounts for hospital readmission? AB - AIMS: This study was launched to address the knowledge gap regarding factors leading to readmission to hospital. BACKGROUND: Repeated hospital admission is an issue of concern for health care service providers. Research findings reveal that multiple factors can contribute to the phenomenon, but no study has examined the direct and indirect effects of these variables on hospital readmission. DESIGN: A survey conducted during the period from 2003-2005 in three hospitals in Hong Kong. METHODS: Patients who were readmitted to the same hospital within 28 days during the study periods were included. Data were collected using structured interviews. A structural equation model was employed to examine what factors will contribute to hospital readmission. RESULTS: The final model showed that subjective health outcome was the only significant variable that had a direct effect on readmission, and it had indirect effects on readmission mediating through the variables of age, income and satisfaction with care. CONCLUSIONS: A literature review reveals that none of the studies has recognised patients' subjective appraisal of their health condition as a significant variable to predict hospital readmission. Results did not find an association between evaluated and perceived need. In other words, patients who felt a higher need for hospital care were not necessarily sicker. It is possible that if patients can be empowered to manage their own health condition and make a fair appraisal of their well-being, unnecessary use of hospital services can be reduced. RELEVANCE TO CLINICAL PRACTICE: This study provides evidence to support the notion that an effective transitional care programme needs to incorporate patients' own subjective assessment of health in the intervention and measurement of the outcome. We cannot solely use providers' judgment to measure health outcomes, for patients are active agents in seeking health care, and the use of services is to an extent self-selective. PMID- 21029228 TI - Literature review: do rapid response systems reduce the incidence of major adverse events in the deteriorating ward patient? AB - AIMS: To conduct a literature review that explores the impact of rapid response systems on reducing major adverse events experienced by deteriorating ward patients. BACKGROUND: Patients located on hospitals wards are frequently older, have multiple co-morbidities and are often at risk of life-threatening clinical deterioration. Rapid response systems have been developed and implemented to provide appropriate and timely intervention to these patients. DESIGN: A comprehensive review of the literature. METHODS: This review used the rapid response systems framework recently developed by experts in the area. Medline, CINAHL, Embase and Cochrane databases were searched from January 1995-June 2009. Sixteen papers were selected that most clearly reflected the research aim. Each paper was critically appraised and systematically assessed. Major themes and findings were identified for each of the studies. RESULTS: The effectiveness of rapid response systems in reducing major adverse events in deteriorating ward patients remains inconclusive. Six studies demonstrated that the introduction of a rapid response systems positively impacted on patient outcomes, but three studies demonstrated no positive impact on patient outcomes. Nursing staff appear reluctant to use rapid response systems; the rationale for this is unclear. However, the continued underuse and inactivation may be one reason why research findings evaluating rapid response systems have been inconclusive. CONCLUSIONS: The paper illustrates two important gaps in the literature. First, 'ramp-up' systems have not been subjected to formal evaluation. Second, rapid response systems are under-activated and underused by nursing staff. There is an urgent need to explore the reasons for this and to identify interventions to improve the activation of these systems in an effort to promote safe and effective care to the deteriorating ward patient. RELEVANCE TO CLINICAL PRACTICE: Rapid response systems are multidimensional models. They are relatively new innovations that have important implications for clinical research and implementation policy. This review contributes to the emerging debate on rapid response systems. PMID- 21029229 TI - Dissemination of research into clinical nursing literature. AB - AIM: The purpose of our study was to describe the dissemination of research into the clinical nursing literature. BACKGROUND: The literature provides a means of transferring knowledge from a research study through citations of the work by other authors. DESIGN: This was a citation analysis study to explore the dissemination of research into the clinical nursing literature, beginning with the publication of an original research study and including all of the citations to that article through 2009. METHODS: The authors searched five academic nursing research journal titles, using CINAHL, for original research reports that had clinical relevance and were published between 1990-1999. The search process yielded a final data set of 28 research articles. For each of the articles, the authors searched three databases, CINAHL, Web of Science((r)) and Google Scholar, to determine the citation patterns from the date of publication to August 2009. RESULTS: All of the research studies were cited in articles published in clinical journals although there was a wide range in the number of citations, from 3-80. The 28 research articles had a total of 759 citations; 717 (94.5%) of those citations were in articles published in clinical nursing journals. The median length of time between publication of the original study and the first citation was 1.5 years. Some of the studies were still being cited for 18 years after publication of the original work. CONCLUSIONS: All of the original research reports examined in this study were cited in articles in clinical journals, disseminating the research beyond the original work to reach clinicians. RELEVANCE TO CLINICAL PRACTICE: Clinical nursing journals keep readers up-to-date and informed about new practices in nursing and serve another important role: they disseminate research that is clinically relevant by publishing original studies and papers that cite research reports. PMID- 21029230 TI - The health of hospitals and lessons from history: public health and sanitary reform in the Dublin hospitals, 1858-1898. AB - AIMS AND OBJECTIVES: The aim was to examine, critically, 19th century hospital sanitary reform with reference to theories about infection and contagion. BACKGROUND: In the nineteenth century, measures to control epidemic diseases focused on providing clean water, removing waste and isolating infected cases. These measures were informed by the ideas of sanitary reformers like Chadwick and Nightingale, and hospitals were an important element of sanitary reform. DESIGN: Informed by the paradigmatic tradition of social history, the study design was a historical analysis of public health policy. METHOD: Using the methods of historical research, documentary primary sources, including official reports and selected hospital archives and related secondary sources, were consulted. RESULTS: Emerging theories about infection were informing official bodies like the Board of Superintendence of Dublin Hospitals in their efforts to improve hospital sanitation. The Board secured important reforms in hospital sanitation, including the provision of technically efficient sanitary infrastructure. CONCLUSIONS: Public health measures to control epidemic infections are only as effective as the state of knowledge of infection and contagion and the infrastructure to support sanitary measures. RELEVANCE TO CLINICAL PRACTICE: Today, public mistrust about the safety of hospitals is reminiscent of that of 150 years ago, although the reasons are different and relate to a fear of contracting antimicrobial-resistant infections. A powerful historical lesson from this study is that resistance to new ideas can delay progress and improved sanitary standards can allay public mistrust. In reforming hospital sanitation, policies and regulations were established--including an inspection body to monitor and enforce standards--the benefits of which provide lessons that resonate today. Such practices, especially effective independent inspection, could be adapted for present-day contexts and re-instigated where they do not exist. History has much to offer contemporary policy development and practice reform and is a relevant method for health professionals. PMID- 21029231 TI - Acute care management of older people with dementia: a qualitative perspective. AB - AIM AND OBJECTIVES: This Australian study explored management for older people with dementia in an acute hospital setting. BACKGROUND: As the population ages, increasing numbers of older people with dementia are placed into an acute care hospital to manage a condition other than dementia. These people require special care that takes into account the unique needs of confused older people. Current nursing and medical literature provides some direction in relation to best practice management; however, few studies have examined this management from the perspective of hospital staff. DESIGN: A descriptive qualitative approach was used. METHOD: Data were collected using semi-structured audio-taped interviews with a cross section of thirteen staff that worked in acute medical or surgical wards in a large South East Queensland, Australia Hospital. RESULTS: Analysis of data revealed five subthemes with the overarching theme being paradoxical care, in that an inconsistent approach to care emphasised safety at the expense of well being and dignity. A risk management approach was used rather than one that incorporated injury prevention as one facet of an overall strategy. CONCLUSION: Using untrained staff to sit and observe people with dementia as a risk management strategy does not encourage an evidence-based approach. Staff education and environmental resources may improve the current situation so that people with dementia receive care that takes into account their individual needs and human dignity. RELEVANCE TO CLINICAL PRACTICE: Nurses can assist older people with dementia by encouraging evidence-based care practices to become the part of hospital policy. PMID- 21029232 TI - Hormone receptor-like in 96 and Broad-Complex modulate phenobarbital induced transcription of cytochrome P450 CYP6D1 in Drosophila S2 cells. AB - Phenobarbital (PB) is a prototypical inducer for studies of xenobiotic responses in animals. In mammals, the nuclear receptors constitutive androstane receptor (CAR) and pregnane X receptor (PXR) have been identified as key transcription factors regulating PB induced transcription of xenobiotic responsive genes. In insects, much less is known about the transcription factors involved in regulating PB induced transcription, although CAR and PXR have a single orthologue hormone receptor-like in 96 (HR96) in Drosophila melanogaster. Using dual luciferase reporter assays in Drosophila Schneider (S2) cells, constructs containing variable lengths of the promoter of the PB inducible cytochrome P450 CYP6D1 were evaluated in the presence and absence of PB. The promoter region between -330 and -280 (relative to the position of transcription start site, +1) was found to be critical for PB induction. Putative binding sites for Drosophila Broad-Complex (BR-C) and deformed (Dfd) were identified within this promoter region using TFsearch. RNA interference (RNAi) treatment of S2 cells in conjunction with CYP6D1 promoter assays showed that suppression of Drosophila HR96 and BR-C transcription in S2 cells resulted in a significant decrease and increase, respectively, of PB induction. Effects of HR96 and BR-C in mediating PB induction were PB specific and PB dependent. This represents new functional evidence that Drosophila HR96 and BR-C can act as an activator and repressor, respectively, in regulating PB induced transcription in insects. PMID- 21029233 TI - The effect of configuration on VSWM performance of Down syndrome individuals. AB - BACKGROUND: Recent studies have demonstrated that individuals with Down syndrome (DS) are poorer than controls in spatial-simultaneous tasks, but not in spatial sequential tasks. To explain this finding, it has been suggested that the simultaneous visuo-spatial working memory deficit of individuals with DS could be due to the request for processing more than one item at a time. The present study examines the possibility of reducing the difficulties encountered by DS individuals on spatial-simultaneous tasks by proposing a task that uses structured material. METHOD: Two tasks were administered to 20 children and adolescents with DS, and 20 controls matched for verbal mental age. The tasks involved memorising and recalling filled-cell positions in a series of matrices in which an increasing number of cells (1-7) were filled. In the structured condition the filled cells were displayed to form a pattern, whereas in the random condition they were randomly arranged. RESULTS AND CONCLUSIONS: Results showed that individuals with DS are able to take advantage of structured material for raising their performance, but to a less extent than typically developing children. PMID- 21029234 TI - Choice of living arrangements. AB - BACKGROUND: The rights to choose where and with whom to live are widely endorsed but commonly denied to adults with intellectual disabilities (ID). The current study provides a contemporary benchmark on the degree of choice exercised by adult service users in the USA. METHOD: Data came from the National Core Indicators programme. Participants were 6778 adult service users living in non family-home service settings in 26 US states. RESULTS: Most adults with ID did not participate in choosing where and with whom to live. Those with more support needs because of more severe ID and/or co-occurring conditions experienced less choice regarding living arrangements. Individuals living in their own home or an agency-operated apartment were more likely to choose where and with whom to live than individuals in nursing homes, institutions or group homes. However, few individuals with severe or profound ID chose where and with whom to live regardless of where they lived. CONCLUSIONS: In 2008, despite community-living policies that emphasise choice, many adult service users with ID in the USA experienced little or no choice about where and with whom to live, especially those individuals with more severe ID. Our findings provide a clear endorsement of policies promoting more individualised living settings, such as one's own home or an agency apartment, because these settings do provide substantially more choice about living arrangements. PMID- 21029235 TI - Participation in daytime activities among people with mild or moderate intellectual disability. AB - BACKGROUND: Community participation has been defined as performing daytime activities by people while interacting with others. Previous studies on community participation among people with intellectual disability (ID) have mainly focused on the domestic life aspect. This study investigates the variation in community participation in the domains work, social contacts and leisure activities among people with ID in the Netherlands. A number of categories of people with ID were distinguished by: (1) gender; (2) age; (3) type of education; (4) severity of ID; and (5) accommodation type. METHODS: Data were gathered on 653 people with mild or moderate ID, of whom 513 by oral interviews and 140 by structured questionnaires filled in by representatives of those who could not be interviewed. Pearson chi-square tests were used to test differences between categories of people with ID in the distributions of the participation variables. Additional logistic regression analyses were conducted to correct for differences between the categories in other variables. RESULTS: Most people with mild or moderate ID in the Netherlands have work or other daytime activities, have social contacts and have leisure activities. However, people aged 50 years and over and people with moderate ID participate less in these domains than those under 50 years and people with mild ID. Moreover, people with ID hardly participate in activities with people without ID. CONCLUSION: High participation among people with a mild or moderate ID within the domains of work, social contact and leisure activities does not necessarily indicate a high level of interaction with the community, because the majority hardly interact with people without ID. Furthermore, older people with ID and people with a more severe level of ID seem to be more at risk for social exclusion. PMID- 21029236 TI - Post-mating reproductive barriers in two unidirectionally hybridizing sunfish (Centrarchidae: Lepomis). AB - The evolutionary sequence of events in the evolution of reproductive barriers between species is at the core of speciation biology. Where premating barriers fail, post-mating barriers, such as conspecific sperm precedence (CSP), gamete incompatibility (GI) and hybrid inviability (HI) may evolve to prevent the production of (often) costly hybrid offspring with reduced fitness. We tested the role of post-mating mechanisms for the reproductive isolation between two sunfish species [bluegill (BG) Lepomis macrochirus and pumpkinseed (PS) Lepomis gibbosus] and their first-generation hybrids. Performing in vitro sperm competition experiments, we observed asymmetric CSP as main post-mating isolation mechanism when BG and PS sperm were competing for PS eggs, whereas when sperm from both species were competing for BG eggs it was HI. Furthermore, hybrid sperm--although fertile in the absence of competition--were outcompeted by sperm of either parental species. This result may at least partly explain previous observations that natural hybridization in the study system is unidirectional. PMID- 21029237 TI - Modulation of tau phosphorylation by the kinase PKR: implications in Alzheimer's disease. AB - Double-stranded RNA dependent kinase (PKR) is a pro-apoptotic kinase that controls protein translation. Previous studies revealed that activated PKR is increased in brains with Alzheimer's disease (AD). Glycogen Synthase Kinase Abeta (GSK-3beta) is responsible for tau phosphorylation and controls several cellular functions also including apoptosis. The goal of this work was to determine if PKR could concurrently trigger GSK-3beta activation, tau phosphorylation and apoptosis. In AD brains, both activated kinases co-localize with phosphorylated tau in neurons. In SH-SY5Y cell cultures, tunicamycin and Abeta(1-42) activate PKR, GSK-3beta and induce tau phosphorylation and all these processes are attenuated by PKR inhibitors or PKR siRNA. Our results demonstrate that neuronal PKR co-localizes with GSK-3beta and tau in AD brains and is able to modulate GSK 3beta activation, tau phosphorylation and apoptosis in neuroblastoma cells exposed to tunicamycin or Abeta. PKR could represent a crucial signaling point relaying stress signals to neuronal pathways leading to cellular degeneration in AD. PMID- 21029238 TI - Mutation analysis of CCM1, CCM2 and CCM3 genes in a cohort of Italian patients with cerebral cavernous malformation. AB - Cerebral cavernous malformations (CCMs) are vascular lesions of the CNS characterized by abnormally enlarged capillary cavities. CCMs can occur as sporadic or familial autosomal dominant form. Familial cases are associated with mutations in CCM1[K-Rev interaction trapped 1 (KRIT1)], CCM2 (MGC4607) and CCM3 (PDCD10) genes. In this study, a three-gene mutation screening was performed by direct exon sequencing, in a cohort of 95 Italian patients either sporadic or familial, as well as on their at-risk relatives. Sixteen mutations in 16 unrelated CCM patients were identified,nine mutations are novel: c.413T > C; c.601C > T; c.846 + 2T > G; c.1254delA; c.1255-4delGTA; c.1682-1683 delTA in CCM1; c.48A > G; c.82-83dupAG in CCM2; and c.395 + 1G > A in CCM3 genes [corrected].The samples, negative to direct exon sequencing, were investigated by MLPA to search for intragenic deletions or duplications. One deletion in CCM1 exon 18 was detected in a sporadic patient. Among familial cases 67% had a mutation in CCM1, 5.5% in CCM2, and 5.5% in CCM3, whereas in the remaining 22% no mutations were detected, suggesting the existence of either undetectable mutations or other CCM genes. This study represents the first extensive research program for a comprehensive molecular screening of the three known genes in an Italian cohort of CCM patients and their at-risk relatives. PMID- 21029239 TI - Selective inhibition of early--but not late--expressed HIF-1alpha is neuroprotective in rats after focal ischemic brain damage. AB - The expression of hypoxia-inducible factor-1-alpha (HIF-1alpha) is upregulated in ischemic stroke, but its function is still unclear. In the present study, biphasic expression of HIF-1alpha was observed during 1-12 h and after 48 h in neurons exposed to ischemic stress in vitro and in vivo. Treating neurons with 2 methoxyestradiol (2ME2) 0.5 h after ischemic stress or pre-silencing HIF-1alpha with small interfering RNA (siRNA) decreased brain injury, brain edema and number of apoptotic cell, and downregulates Nip-like protein X (Nix) expression. Conversely, applying 2ME2 to neurons 8 h after ischemic stress or silencing the HIF-1alpha with siRNA 12 h after oxygen-glucose deprivation (OGD) increased neuron damage and decreased vascular endothelial growth factor (VEGF) expression. Taken together, these results demonstrate that HIF-1alpha induced by ischemia in early and late times leads cellular apoptosis and survival, respectively, and provides a new insight into the divergent roles of HIF-1alpha expression in neurons after ischemic stroke. PMID- 21029242 TI - Rescuing success from the jaws of defeat. PMID- 21029240 TI - An animal model of cortical and callosal pathology in multiple sclerosis. AB - The pathological and radiological hallmarks of multiple sclerosis (MS) include multiple demyelinated lesions disseminated throughout the white matter of the central nervous system (CNS). More recently, the cerebral cortex has been shown to be affected in MS, but the elucidation of events causing cortical demyelination has been hampered by the lack of animal models reflecting such human cortical pathology. In this report, we have described the presence of cortical gray matter and callosal white matter demyelinating lesions in the chronic experimental autoimmune encephalomyelitis (EAE) mouse model of MS. Similar to the pathological lesions of MS patients, EAE lesions have been classified as type I-leukocortical, type II-intracortical and type III-subpial. All of these lesions had varying degrees of demyelination, inflammatory cells and reactive astrocytes. Similar to MS, cortical layers during EAE showed demyelination, microglia activation, synaptic protein alterations and apoptotic cells. In addition, the callosal white matter during EAE had many inflammatory demyelinating lesions and axon degeneration. Functional electrophysiological conduction analysis showed deficits in both myelinated and unmyelinated callosal axons during early and late EAE. The chronic EAE mouse model has features that mimic cortical and callosal pathology of MS, and can be potentially used to screen agents to prevent these features of disease. PMID- 21029243 TI - Correlation of polydispersed prion protein and characteristic pathology in the thalamus in variant Creutzfeldt-Jakob disease: implication of small oligomeric species. AB - The vacuolation, neuronal loss and gliosis that characterize human prion disease pathology are accompanied by the accumulation of an aggregated, insoluble and protease-resistant form (termed PrP(Sc)) of the host-encoded normal cellular prion protein (PrP(C)). In variant Creutzfeldt-Jakob disease the frontal cortex and cerebellum exhibit intense vacuolation and the accumulation of PrP(Sc) in the form of amyloid plaques and plaque-like structures. In contrast the posterior thalamus is characterized by intense gliosis and neuronal loss, but PrP(Sc) plaques are rare and vacuolation is patchy. We have used sucrose density gradient centrifugation coupled with conformation dependent immunoassay to examine the biochemical properties of the PrP(Sc) that accumulates in these different brain regions. The results show a greater degree of PrP(Sc) polydisperal in thalamus compared with frontal cortex or cerebellum, including a subpopulation PrP(Sc) molecules in the thalamus that have sedimentation properties resembling those of PrP(C). Much effort has focused on identifying aspects of PrP(Sc) biochemistry that distinguish between different forms of human prion disease and contribute to differential diagnosis. Here we show that PrP(Sc) sedimentation properties, which can depend on aggregation state, correlate with, and may underlie the distinct neurodegenerative processes occurring in different regions of the variant Creutzfeldt-Jakob disease brain. PMID- 21029241 TI - Neuronal MCP-1 mediates microglia recruitment and neurodegeneration induced by the mild impairment of oxidative metabolism. AB - Chemokines are implicated in the neuroinflammation of several chronic neurodegenerative disorders. However, the precise role of chemokines in neurodegeneration is unknown. Thiamine deficiency (TD) causes abnormal oxidative metabolism in the brain as well as a well-defined microglia activation and neurodegeneration in the submedial thalamus nucleus (SmTN), which are common features of neurodegenerative diseases. We evaluated the role of chemokines in neurodegeneration and the underlying mechanism in a TD model. Among the chemokines examined, TD selectively induced neuronal expression of monocyte chemoattractant protein-1 (MCP-1) in the SmTN prior to microglia activation and neurodegeneration. The conditioned medium collected from TD-induced neurons caused microglia activation. With a neuron/microglia co-culture system, we showed that MCP-1-induced neurotoxicity required the presence of microglia, and exogenous MCP-1 was able to activate microglia and stimulated microglia to produce cytokines. A MCP-1 neutralizing antibody inhibited MCP-1-induced microglia activation and neuronal death in culture and in the thalamus. MCP-1 knockout mice were resistant to TD-induced neuronal death in SmTN. TD selectively induced the accumulation of reactive oxygen species in neurons, and antioxidants blocked TD-induced MCP-1 expression. Together, our results indicated an induction of neuronal MCP-1 during mild impairment of oxidative metabolism caused by microglia recruitment/activation, which exacerbated neurodegeneration. PMID- 21029244 TI - The nature and timing of specific copy number changes in the course of molecular progression in diffuse gliomas: further elucidation of their genetic "life story". AB - Up till now, typing and grading of diffuse gliomas is based on histopathological features. However, more objective tools are needed to improve reliable assessment of their biological behavior. We evaluated 331 diffuse gliomas for copy number changes involving 1p, 19q, CDKN2A, PTEN and EGFR(vIII) by Multiplex Ligation dependent Probe Amplification (MLPA(r), Amsterdam, The Netherlands). Specifically based on the co-occurrence of these aberrations we built a model for the timing of the different events and their exact nature (hemi- -> homozygous loss; low level gain -> (high-copy) amplification) in the course of molecular progression. The mutation status of IDH1 and TP53 was also evaluated and shown to correlate with the level of molecular progression. The relevance of the proposed model was confirmed by analysis of 36 sets of gliomas and their 39 recurrence(s) whereas survival analysis for anaplastic gliomas confirmed the actual prognostic relevance of detecting molecular malignancy. Moreover, based on our results, molecular diagnostic analysis of 1p/19q can be further improved as different aberrations were identified, some of them being indicative for advanced molecular malignancy rather than for favorable tumor behavior. In conclusion, identification of molecular malignancy as proposed will aid in establishing a risk profile for individual patients and thereby in therapeutic decision making. PMID- 21029245 TI - Study on the relationship between Th17 cells and unexplained recurrent spontaneous abortion. AB - PROBLEM: What is the relationship between Th17 cells and unexplained recurrent spontaneous abortion (URSA)? METHOD OF STUDY: CD4(+) interleukin (IL)-17A(+) T (Th17) cells and CD4(+) CD25(bright) Foxp3(+) regulatory T (Treg) cells in peripheral blood were analyzed by flow cytometry; IL-17 concentrations in cell culture supernatants were quantitatively determined by enzyme-linked immunosorbent assay; and IL-17A positive cells in decidua tissues were measured by immunohistochemistry. RESULTS: The proportion of Th17 cells and IL-17A concentrations was both significantly higher in patients with URSA than in normal early pregnant (NEP) and non-pregnant (NP) patients, Treg frequencies were significantly lower in patients with URSA than in NEP patients, and the ratio of Th17 to Treg was significantly higher in the URSA group than in the other two. Additionally, the percentage of IL-17A cells in deciduas was significantly higher in patients with URSA than in NEP patients. CONCLUSIONS: Human Th17 cells may play a major role in rejecting conceptus antigens and therefore may be harmful to the maintenance of pregnancy. The data also suggest that Treg cells are beneficial to pregnancy. There may exist a balance of Th17/Treg in normal pregnancy. PMID- 21029246 TI - Induction of APS after TTd hyper-immunization has a different outcome in BALB/c and C57BL/6 mice. AB - PROBLEM: The antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by vascular thrombosis and/or pregnancy complications (lower fecundity and lower litter size), as well as by an increase in anti-beta(2) glycoprotein I (beta(2) GPI)-specific autoantibody titer. We have investigated how the genetic background of the immune system [T helper (Th) prevalence] and the type of animal model of APS influence the induced pathology. METHOD OF STUDY: Antiphospholipid syndrome induced by tetanus toxoid (TTd) hyper-immunization and by intravenous application of monoclonal anti-beta(2) GPI-specific antibody 26 was compared in C57BL/6 (Th1 prone) and BALB/c (Th2 prone) mice. RESULTS: Tetanus toxoid hyper-immunization of BALB/c mice led to reduction in fertility, but in C57BL/6 mice a decrease in fecundity occurred. In both cases, pathology was caused by anti-beta(2) GPI antibodies, the production of which was adjuvant and strain dependent. CONCLUSION: We conclude that TTd immunization and i.v. application of monoclonal antibody 26 induced the same reproductive pathology and that the type of pathology is strain dependent. PMID- 21029247 TI - How is evidence on test performance synthesized for economic decision models of diagnostic tests? A systematic appraisal of Health Technology Assessments in the UK since 1997. AB - OBJECTIVES: The study aims to assess how evidence on diagnostic test accuracy is synthesized and used to inform economic decision modeling for HTA. METHODS: All reports evaluating diagnostic test via an economic decision model published by the NHS Research and Development Health Technology Assessment (HTA) program since 1997 were identified. The methods for evidence synthesis of diagnostic test accuracy data and its use in economic decision modeling in this sample were reviewed. RESULTS: Forty-four HTA reports out of 474 concerned diagnostic accuracy, of which 11 did not do any economic evaluation. Of the remaining 33 HTAs, 14 conducted meta-analyses of diagnostic accuracy in the clinical review but only 8 used such pooled estimates to inform the decision model. A number of meta-analysis methods ranging in complexity were applied to estimate diagnostic accuracy. Nevertheless, when it came to informing the economic decision model, the majority of reviews used independent meta-analytic estimates of sensitivity and specificity. CONCLUSIONS: Often, very simplistic methods to estimate diagnostic test accuracy were used for purposes of informing an economic decision model. The assumptions made by the simplistic methods are usually invalid which may lead to suboptimal decisions being made. It is desirable that decision modelers become aware of the rapid evolution of meta-analysis methods in this area; however, further research is still required to identify how the pooled results obtained from the different meta-analysis models should best be used to inform economic decision models. PMID- 21029248 TI - The cyclohexane tolerance and Phe-Arg-beta-naphtylamide susceptibility of multidrug-resistant Enterobacter cloacae clinical isolates, and the predominance of one PFGE clone in Hungary. AB - The report concerns the molecular epidemiology, cyclohexane tolerance and Phe-Arg beta-naphtylamide (PAbetaN) susceptibility of multidrug-resistant Enterobacter cloacae isolates, with high-level fluoroquinolone resistance collected from healthcare facilities in a nationwide survey. A total of 113 multidrug-resistant E. cloacae isolates (recovered in 1997-2005) were subjected to disc diffusion tests, ERIC-PCR and XbaI PFGE. Representatives of the ERIC-types (n = 67) were tested further with cyclohexane and PAbetaN, using ciprofloxacin as the substrate. Forty-four per cent of the isolates were derived from the urinary tract, 19% from the bloodstream, 17% from the respiratory tract, and 15% from wound infections. Four ERIC-types (A, B, C and D) were distinguished, but 109 isolates were found to belong to a single, epidemic ERIC type: A. PFGE results suggested that the epidemic-type isolates were of monoclonal origin. Forty-two patients were involved in four outbreaks caused by the epidemic-type strains. Eighty-one cases were found to be nosocomial. At least fourfold reduction in ciprofloxacin MICs was found in the presence of PAbetaN in 79% of representative isolates (representing types A, C and D); an eightfold or greater reduction in ciprofloxacin MICs in the presence of PAbetaN (PAbetaN+) was found in 37% of representative isolates, representing types A and C. Eighty-five per cent of the representative isolates were found to be cyclohexane-tolerant, representing types A, C and D. This is the first report of a wide distribution of cyclohexane tolerant or PAbetaN+ strains of E. cloacae. These feature-indicators of adaptive mechanisms that help bacteria to survive in hospital wards may have contributed to the nationwide spread of type A strains. PMID- 21029249 TI - Dorsal hippocampal opioidergic system modulates anxiety-like behaviors in adult male Wistar rats. AB - AIMS: In the present study, we investigated the possible influence of the opioidergic system of the dorsal hippocampus on anxiety-like behaviors. METHODS: Elevated plus-maze, which is one of the methods used for testing anxiety, was used in the present study. Rats were anesthetized with ketamine and xylazine and special cannulas were inserted stereotaxically into the CA1 region of the dorsal hippocampus. After 1 week of recovery, the effects of intra-CA1 administration of morphine (0.25, 0.5, 1 and 2 ug/rat; 1 ul/rat; 0.5 ul/in each side), naloxone (2, 4, 6 and 8 ug/rat), enkephalin (1, 2, 5 and 10 ug/rat) and naltrindole (0.25, 0.5, 1 and 2 ug/rat) on percentage open arm time (%OAT) and percentage open arm entries (%OAE) were determined. RESULTS: Bilateral administration of morphine into CA1 decreases %OAT and %OAE, indicating an anxiogenic-like effect. Intra-CA1 injection of naloxone, an opioid receptor antagonist, increased both %OAT and %OAE, parameters of anxiolytic-like behavior. Bilateral administration of delta opioid receptor agonist, [D-Pen(2,5) ]-enkephalin acetate hydrate into the CA1, induced an anxiolytic-like effect. Furthermore, intra-CA1 injection of delta opioid receptor antagonist, naltrindole hydrochloride, increased anxiety-related behaviors. CONCLUSIONS: The results of the present study demonstrate that activation of MU-opioid receptors in this area produce an anxiogenic response while activation of delta-opioid receptors produces an anxiolytic response. PMID- 21029250 TI - Serum ghrelin is inversely associated with cognitive function in a sample of non demented elderly. AB - AIM: The orexigenic hormone, ghrelin, is linked to learning and memory in animal studies. No previous study has investigated whether cognition is related to ghrelin in the non-demented elderly. METHODS: Thirty-five older adults underwent neuropsychological testing and fasting blood draw with subsequent serum ghrelin quantification. RESULTS: Ghrelin was negatively correlated with several cognitive domains, including verbal memory, working memory, and naming. CONCLUSION: Areas of cognition associated with ghrelin level were similar to the pattern of deficits observed in early Alzheimer's disease. Findings suggest a potential moderational role of ghrelin in pathological cognitive decline. Further work investigating mechanisms is needed. PMID- 21029251 TI - Syndrome of inappropriate anti-diuretic hormone in Kawasaki disease. AB - BACKGROUND: The pathogenesis of hyponatremia in acute Kawasaki disease (KD) remains unclear. A recent case report of KD complicated by syndrome of inappropriate anti-diuretic hormone (SIADH) led us to determine the prevalence of SIADH in acute KD patients. METHODS: Subjects were 39 Japanese KD patients (2-84 months of age, 25 males and 14 females) treated with intravenous immunoglobulin (IVIG), 2 g/kg/day and oral aspirin. SIADH was defined when hyponatremic patients (serum sodium concentration <135 mEq/L) had decreased serum osmolality <280 mOsm/kg H(2) O, elevated urine sodium concentration >20 mEq/L and elevated urine osmolality >100 mOsm/kg H(2) O without dysfunctions of renal, thyroid or adrenal gland. We also studied the relation between clinical course of SIADH and the amount of infused fluid during IVIG. RESULTS: Before IVIG, 27 patients (69%) had hyponatremia and 11 (28% of total; 41% of hyponatremic patients) had SIADH while after IVIG, 13 (33%) hyponatremia and four (10%; 31% of hyponatremic patients) SIADH. Among 11 patients with SIADH before IVIG, SIADH improved in 10 after IVIG, but hyponatremia persisted in five. Significant correlation was observed between serum sodium concentration after IVIG and infusion amount in SIADH patients (r= 0.64, P= 0.03), but not in non-SIADH patients. CONCLUSIONS: This is the first report to show that SIADH is common as a cause of hyponatremia in acute KD and hence careful management of water and sodium is warranted. PMID- 21029253 TI - Neural stem cells: properties and therapeutic potentials for hypoxic-ischemic brain injury in newborn infants. AB - Neural stem cells (NSCs) are defined by their ability to self-renew, to differentiate into cells of all glial and neuronal lineages throughout the neuraxis, and to populate developing or degenerating central nervous system (CNS) regions. The recognition that NSCs propagated in culture could be reimplanted into the mammalian brain, where they might integrate appropriately throughout the mammalian CNS and stably express foreign genes, has unveiled a new role for neural transplantation and gene therapy and a possible strategy for addressing the CNS manifestations of diseases that hitherto had been refractory to intervention. An intriguing phenomenon with possible therapeutic potentials has begun to emerge from our observations of the behavior of NSCs in animal models of neonatal hypoxic-ischemic (HI) brain injury. During phases of active neurodegeneration, factors seem to be transiently elaborated to which NSCs may respond by migrating to degenerating regions and differentiating specifically towards replacement of dying neural cells. NSCs may attempt to repopulate and reconstitute ablated regions. These 'repair mechanisms' may actually reflect the reexpression of basic developmental principles that may be harnessed for therapeutic ends. In addition, NSCs may serve as vehicles for gene delivery and appear capable of simultaneous neural cell replacement and gene therapy (e.g. with factors that might enhance neuronal differentiation, neurites outgrowth, proper connectivity, and/or neuroprotection). When combined with certain synthetic biomaterials, NSCs may be even more effective in 'engineering' the damaged CNS towards reconstitution. We have also cultured human NSCs or progenitors as neurospheres which were derived from fetal cadavers at 13 weeks of gestation, and transplanted them into HI-injured immature brains to investigate their therapeutic potentials in this type of model. PMID- 21029252 TI - Transient hyperphosphatasemia in children revisited. AB - OBJECTIVE: Although transient hyperphosphatasemia (TH) has been well known for decades, its etiology and pathophysiology remain unclear. We aimed to study the clinical characteristics of children diagnosed with TH compared to older studies in order to expand our knowledge and understanding of this condition and to try and find a subgroup of children who are more prone to develop TH. METHODS: We retrospectively studied 60 children diagnosed at Maccabi Health Services and Bnai Zion Medical Center, Haifa, Israel with TH between the years 2003-08. One hundred and twenty-two children matched by age, gender and presenting symptoms served as the control group. The patients were divided into four subgroups by their presenting symptoms: infectious disease 33%, failure to thrive 28%, diarrhea 15% and other 23%. The Hydragel 7 ISO-PAL and Hydragel 15 ISO-PAL kits were used for the identification and quantification of ALP isoenzymes in human serum. RESULTS: The ALP levels of the study group were 805-8619 U?L (mean 2311 U?L), without differences between the subgroups. The mean duration of TH was 12 weeks. ALP isoenzymes levels were measured in one-third of the patients, and showed that the bone isoenzyme was elevated in most. Forty-three (71%) subjects were diagnosed in the second half of the calendar year. CONCLUSIONS: We could not establish an etiological explanation for TH. We presume that it is a complex mechanism in which different stimuli led to upregulation of the enzyme. PMID- 21029254 TI - Calcium-binding protein S100P is a novel diagnostic marker of cholangiocarcinoma. AB - The incidence and mortality of cholangiocarcinoma are increasing despite improvements in the diagnostic method. Since the sensitivity of brushing cytology for cholangiocarcinoma is not satisfactory, a novel diagnostic marker needs to be established. A recent report has suggested upregulation of the calcium-binding protein S100P in cholangiocarcinoma. The expression status of S100P in normal bile duct and cholangiocarcinoma tissues was assessed by immunohistochemistry. The expression levels of S100P mRNA in the brushing cytology samples during endoscopic retrograde cholangiopancreatography (ERCP) from benign biliary strictures and cholangiocarcinoma were assessed by real-time reverse transcription-polymerase chain reaction (RT-PCR). The sensitivity and specificity of each diagnostic strategy was compared. S100P was frequently expressed in the cholangiocarcinoma tissues, but not in the normal bile duct. The brushing cytology samples from the cholangiocarcinoma cases revealed higher expression levels of S100P compared with the benign biliary strictures. The relative expression level of S100P could determine the cholangiocarcinoma at higher sensitivity than classical cytology, and the combination of the S100P expression level and cytology yielded a sensitivity of 90.0%, with a specificity of 92.0%. Calcium-binding protein S100P is a novel marker of cholangiocarcinoma. Detecting the S100P expression levels in brushing cytology samples has a diagnostic value, which will be helpful for better diagnosis of cholangiocarcinoma. PMID- 21029255 TI - The prevalence of significant liver fibrosis and cirrhosis in haemophilia patients infected with hepatitis C using FibroScan. PMID- 21029256 TI - The effect of the respiratory cycle on liver stiffness values as measured by transient elastography. AB - The findings of several studies suggest that liver stiffness values can be affected by the degree of intrahepatic congestion respiration influence intrahepatic blood volume and may affect liver stiffness. We evaluated the influence of respiration on liver stiffness. Transient elastography (TE) was performed at the end of inspiration and at the end of expiration in patients with chronic liver disease. The median values obtained during the inspiration set and during the expiration set were defined as inspiratory and expiratory liver stiffness, respectively. A total of 123 patients with chronic liver disease were enrolled (mean age 49years; 64.2% men). Liver cirrhosis coexisted in 29 patients (23.6%). Expiratory liver stiffness was significantly higher than inspiratory liver stiffness (8.7 vs 7.9kPa, P=0.001), while the expiratory interquartile range/median ratio (IQR ratio) did not differ from the inspiratory IQR ratio. Expiratory liver stiffness was significantly higher than inspiratory liver stiffness in 49 (39.8%) patients (HE group), expiratory liver stiffness was significantly lower than inspiratory stiffness in 15 (12.2%) patients, and there was no difference in 59 (48.0%) patients. Liver cirrhosis was more frequent in those who had a lower liver stiffness reading in expiration, and only the absence of liver cirrhosis was significantly associated with a higher reading in expiration in multivariate analysis. In conclusion, liver stiffness was significantly elevated during expiration especially in patients without liver cirrhosis. The effect of respiration should be kept in mind during TE readings. PMID- 21029257 TI - Uptake of hepatitis C antibody testing in patients with end-stage liver disease in Glasgow, 1993-2007. AB - Individuals infected with hepatitis C virus (HCV) need to be diagnosed well before developing end-stage liver disease to benefit from treatment. We aimed to ascertain what proportion of cases had been tested for HCV to inform on the effectiveness of current guidelines. Record linkage between national databases of HCV tests, hospital discharges and deaths identified 10,645 persons who were hospitalized or had died with mention of end-stage liver disease in Glasgow, Scotland, between 1993 and 2007. We estimated HCV test uptake and prevalence of HCV infection within the study population. The associations between both HCV test uptake and HCV-antibody status and sex, age group and deprivation quintile were estimated using logistic regression. We found that 43% of those hospitalized (n = 9153) and 23% of those who otherwise died (n = 1492) with first-time mention of end-stage liver disease had been tested for HCV during this period. Test uptake in those hospitalized increased from 13 (95% CI: 12-14%) in 1993-1997 to 58% (56 59%) in 2003-2007. The adjusted odds of being tested for HCV were significantly higher for men (OR=1.3, 95% CI: 1.2-1.5), for ages 25-54 (25-34 years: 2.7, 95% CI: 2.1-3.4; 35-44 years: 2.3, 95% CI: 2.0-2.6; 45-54 years: 1.5, 95% CI: 1.4 1.7) compared with 55+ years, and for those residing in the two most deprived quintiles (1.1, 95% CI: 1.0-1.2). Twenty-eight per cent of the HCV testees aged 25-44 years were HCV infected. These results highlight the continuing need for raising awareness among medical professionals for comprehensive HCV testing in patients with liver disease. PMID- 21029258 TI - Investigating the relationship between hyposalivation and mucosal wetness. AB - BACKGROUND: Mucosal wetness (MW) reflects the layer of residual saliva that covers the oral mucosal surfaces. OBJECTIVES: The aim of this study was to determine MW at different oral mucosa sites and to investigate the relationship between MW, unstimulated whole salivary flow rates (UWS) and Clinical Oral Dryness Score (CODS). METHOD: A total of 100 dry mouth patients and 50 healthy subjects participated in the study. MW was sampled with filter paper strips at four sites inside the mouth; anterior hard palate (AHP), buccal mucosa (BUC), anterior tongue (AT), lower lip (LL) and measured with a micro-moisture meter. Reproducibility was assessed by repeated sampling and diurnal variation was examined. RESULTS: Mucosal wetness in healthy subjects differed according to site and means+/-SD were; AHP (11+/- 11.7MUm), BUC (32+/-14.8MUm), AT (65+/-17.2MUm), and LL (25 +/-13.5MUm). Dry mouth patients with reduced UWS showed increased CODS. MW at all four sites was significantly reduced (P<0.05) in dry mouth patients compared with the healthy subjects. Reproducibility of MW measurement using the intra-class correlation coefficient showed agreement at different visits within subject. MW of the AT showed a positive correlation with UWS (P<0.05). CONCLUSION: Mucosal wetness is a reliable measure of oral dryness and had a positive correlation with UWS. PMID- 21029259 TI - Sialoadenitis secondary to 131I therapy for well-differentiated thyroid cancer. AB - Radioiodine (131I) is an important therapy for patients who have well differentiated thyroid cancer. However, 131I may also result in side effects in multiple organs and glands. The glands that are frequently affected are the salivary glands with the major untoward effects including sialoadenitis and increased risk of second primary malignancy. This report will review sialoadenitis secondary to 131I therapy including (1) proposed mechanisms, (2) incidence and clinical presentations, (3) possible approaches to improve prevention, (4) management, and (5) sequelae of sialoadenitis (e.g. xerostomia and salivary duct obstruction). A discussion of second primary malignancies is beyond the scope of this review. With a better understanding of the above, dentists, oral surgeons, otolaryngologists, endocrinologists, nuclear medicine physicians, and nuclear radiologists will be more likely to implement more effective preventive measures to reduce the incidence and severity of 131I induced sialoadenitis, and if it does occur, to identify and treat sialoadenitis sooner, thereby potentially reducing not only the severity of the initial symptoms, but also the severity of subsequent sequelae. PMID- 21029260 TI - HIV infection and periodontal diseases: an overview of the post-HAART era. AB - HIV infection remains a global health problem of unprecedented dimensions, although the development of highly active antiretroviral therapy (HAART) has significantly modified the course of HIV disease into a manageable chronic disease with longer survival and improved quality of life in HIV-infected subjects. Among the HIV-associated infections, oral lesions have been recognized as prominent features since the beginning of the epidemic and continue to be important. Periodontal diseases strongly associated with HIV infection are classified as linear gingival erythema, necrotizing ulcerative gingivitis and necrotizing ulcerative periodontitis and are included among the cardinal oral lesions. Although oral candidiasis appears to be the infection more significantly decreased after the introduction of HAART, the current literature suggests that the prevalence and course of periodontal lesions have also been modified. Higher prevalence of opportunistic microorganisms has been frequently detected in the subgingival flora of HIV-infected individuals, probably due to the immune status of those patients, as colonization and overgrowth of atypical pathogenic species is facilitated by immunosuppression. Additional research is required regarding biological issues such as the role of oral immune factors and periodontal disease in the persistency of HIV infection, the possibility of oral transmission and the re-emerging of HIV infection. PMID- 21029261 TI - Lack of modulatory function of coding nucleotide polymorphism S100A2_185G>A in oral squamous cell carcinoma. AB - OBJECTIVE: S100A2, a Ca(2+) -binding protein with two EF-hands, is a tumor suppressor in oral cancer. Helix III flanking the C-terminal EF-hand is implicated to participate in the interaction of S100A2 and its target(s). The aim of this study was to examine if the coding sequence polymorphism S100A2_185G>A, leading to the peptide 62 substitution of asparagine (AAC, A allele) for serine (AGC, G allele) in helix III, had modulation effects on S100A-mediated tumor suppression. SUBJECTS AND METHODS: We sequenced the coding sequence of S100A2 gene in normal oral keratinocytes (NOKs), dysplastic oral keratinocytes (DOKs), eight oral cancer lines, and 54 pairwise oral cancer specimens. We also compared the in vitro anti-tumor effect of wildtype (G allele) and variant (A allele) S100A2 expression using cell proliferation, migration, invasion, and colony formation assays. RESULTS: With the exception of CAL27 and SCC-15 cancer lines being heterozygotes of A and G alleles, the remaining oral cells were homozygotic in G alleles. No alterations of anti-growth, anti-migration, anti-invasion, and anti-colony formation were observed between variant and wildtype cells. Moreover, no minor S100A2_185A allele was detected in 54-pairwise clinical specimens. CONCLUSION: The coding sequence polymorphism S100A2_185G>A had no regulatory role in S100A2-mediated tumor suppression in oral cancer. PMID- 21029262 TI - Shikonin inhibits tumor invasion via down-regulation of NF-kappaB-mediated MMP-9 expression in human ACC-M cells. AB - OBJECTIVE: The aim of this study was to examine the anti-invasion effect of Shikonin on human high-metastatic adenoid cystic carcinoma (ACC-M) cells and to explain the possible molecular mechanism involved. METHODS: The ACC-M cells were treated with Shikonin (0, 2.5, 5, 10 MUM) for 24 h. The protein levels and gelatinolytic activities of MMP-2 and MMP-9 were analyzed using Western blot and Gelatin zymography test, respectively. Matrigel invasion assays were used to investigate tumor invasive potential and electromobility shift assays were used to determine the activity of NF-kappaB. RESULTS: The invasiveness of ACC-M cells was reduced in a dose dependent manner following 24-h treatment of up to 10 MUM of the Shikonin at which concentration no cytotoxicity occurred. The protein levels and gelatinolytic activities of MMP-9 were significantly suppressed by increasing Shikonin concentrations. The down-regulation of MMP-9 appeared to be via the inactivation of NF-kappaB as the treatment with Shikonin suppressed the protein level of phosphate-IkBa, which was accompanied by a decrease in DNA binding level of the factor. CONCLUSIONS: Shikonin inhibits tumor invasion via downregulation of MMP-9 expression in ACC-M cells. Pharmacologic inhibition of the NF-kappaB-mediated MMP-9 expression by Shikonin might be a powerful treatment option for ACC patients in future. PMID- 21029263 TI - Characterization of aortic aneurysms in cardiovascular disease patients harboring Porphyromonas gingivalis. AB - OBJECTIVE: Porphyromonas gingivalis was recently shown to cause intimal hyperplasia in a mouse model by a novel cholesterol-independent mechanism, suggesting to be a pathogen-specific feature of cardiovascular diseases. The aim of this study was to characterize the clinical and histopathological features of aortic aneurysms in cardiovascular disease patients harboring oral P. gingivalis. SUBJECT AND METHODS: Aortic aneurysm specimens were collected from 76 Japanese patients who underwent surgery, of whom dental plaque specimens were also collected from 31 patients. Bacterial DNA was extracted from each specimen to detect P. gingivalis by polymerase chain reaction. Histopathological analyses of the aortic aneurysm specimens, including immunohistochemical staining for embryonic myosin heavy chain isoform (SMemb) and S100 calcium-binding protein A9 (S100A9), were also performed. RESULTS: The number of aneurysms occurring in the distal aorta was significantly higher in subjects positive for P. gingivalis in dental plaque compared with those who were negative. The expressions of S100A9 and SMemb were also significantly greater in the subjects positive for P. gingivalis in dental plaque. On the other hand, there were no significant differences in adipocellular accumulation between the groups. CONCLUSIONS: These results suggest that aortic aneurysms in patients harboring oral P. gingivalis have greater expression of S100A9 and proliferative smooth muscle cells, which was different from the present patients without oral P. gingivalis. PMID- 21029264 TI - Identification of the DSPP mutation in a new kindred and phenotype-genotype correlation. AB - OBJECTIVE: Hereditary dentin defects can be grouped into three types of dentinogenesis imperfecta (DGI) and two types of dentin dysplasia. Tooth enamel is considered normal in patients with hereditary dentin defects, but is easily worn down and fractured due to DSPP mutation-induced altered dentin properties. The purposes of this study were to identify genetic cause of a family with type II DGI and enamel defects. MATERIALS AND METHODS: We identified a family with type II DGI and a unique form of hypoplastic enamel defect affecting occlusal third of the crown. Family members were recruited for the genetic analysis and DNA was obtained from peripheral whole blood. RESULTS: Mutational analysis revealed a T to A transversion in exon 3 of the DSPP (c.53T>A, p.V18D). Haplotype analysis showed that the same mutation arose separately in two different families having DGI with similar enamel defects, indicating that this phenotype is associated with this specific DSPP mutation. Clinical features suggest that enamel formation was affected in the affected individuals during early amelogenesis, in addition to the dentin defect. CONCLUSIONS: We observed that a DSPP gene mutation not only influences dentinogenesis but also affects early stage amelogenesis. PMID- 21029265 TI - Root and periodontal tissue development after allogenic tooth transplantation between rat littermates. AB - OBJECTIVE: The study was designed to investigate the development of roots and periodontal tissues after allogenic tooth transplantation between rat littermates by micro-computed tomography (micro-CT) and histology. MATERIALS AND METHODS: The upper right second molars in 2-week-old rats were extracted and immediately transplanted into the upper right first molar socket of rat littermates under anesthesia. The upper left second molars in 2-week-old recipient rats were used as a control. The rats were fixed and tissues analyzed at 0, 4, 8, or 12 weeks after transplantation. Root development of seven rats in each group was analyzed quantitatively using micro-CT. Periodontal tissue formation was examined qualitatively by histologic methods. RESULTS: Roots developed after allogenic transplantation, but they were significantly shorter than control roots. The number of roots varied from one to four in transplanted teeth, while it was consistently four in control teeth. Periodontal tissue formation in transplanted teeth was equivalent to that of the control teeth. CONCLUSION: Allogenic transplantation between rat littermates permits root development and periodontal tissue formation. PMID- 21029266 TI - Cheilitis glandularis: clinico-histopathological diagnostic criteria. AB - OBJECTIVES: To present a combination of clinical and histopathological criteria for diagnosing cheilitis glandularis (CG), and to evaluate the association between CG and squamous cell carcinoma (SCC). MATERIALS AND METHODS: The medical literature in English was searched from 1950 to 2010 and selected demographic data, and clinical and histopathological features of CG were retrieved and analysed. RESULTS: A total of 77 cases have been published and four new cases were added to the collective data. The clinical criteria applied included the coexistence of multiple lesions and mucoid/purulent discharge, while the histopathological criteria included two or more of the following findings: sialectasia, chronic inflammation, mucous/oncocytic metaplasia and mucin in ducts. Only 47 (58.0%) cases involving patients with a mean age of 48.5 +/- 20.3 years and a male-to-female ratio of 2.9:1 fulfilled the criteria. The lower lip alone was most commonly affected (70.2%). CG was associated with SCC in only three cases (3.5%) for which there was a clear aetiological factor for the malignancy. CONCLUSIONS: The proposed diagnostic criteria can assist in delineating true CG from a variety of lesions with a comparable clinical/histopathological presentation. CG in association with premalignant/malignant epithelial changes of the lower lip may represent secondary, reactive changes of the salivary glands. PMID- 21029267 TI - Evaluating service delivery for speech and swallowing problems following paediatric brain injury: an international survey. AB - RATIONALE, AIMS AND OBJECTIVES: Little is documented about contemporary management of speech and swallowing disorders associated with paediatric acquired brain injury (ABI). It is therefore challenging for clinicians in this field to benchmark their clinical management against current evidence or practices undertaken in other centres. To address this issue, we aimed to provide much needed baseline data on speech and language pathology management of speech and swallowing disorders associated with childhood ABI. Key objectives were to: (i) determine whether clinicians use formalized referral criteria, clinical guidelines, protocols or care pathways; and (ii) to document the specific assessment and treatment approaches used. METHODS: Speech and language pathology managers and clinicians at 31 major paediatric rehabilitation centres across Australia, New Zealand, the UK and Ireland were invited to participate in an online survey. RESULTS: Fifty-one speech and language pathologists responded representing 26 centres (84% response rate). Routine referrals of ABI patients to speech and language pathology occurred relatively infrequently in these centres (12%). Centres utilized assessment protocols (23%) and guidelines (35%) more frequently than treatment guidelines (8%). Multidisciplinary care pathways were applied by 31%. Most centres used adult-based motor speech assessments and informal ('in-house developed') swallowing assessment tools. CONCLUSIONS: The limited use of referral criteria, protocols, care pathways and guidelines invites the possibility of unequal care, and less than optimal outcomes. Reliance on adult-based or in-house assessments is inappropriate, yet frequently a necessity due to an absence of paediatric-specific tools in this field. Further research is required in parallel with the formation of consensus groups to support the development of: (i) paediatric-specific assessment tools and management approaches; and (ii) clinical protocols and guidelines. PMID- 21029268 TI - A review of cost-effectiveness of varenicline and comparison of cost effectiveness of treatments for major smoking-related morbidities. AB - RATIONALE: This review aims to examine economic evaluations of varenicline, to compare the reported cost-effectiveness of varenicline with that of treatments for major smoking-related diseases and to evaluate the findings for decision making. METHODS: A literature search was performed to identify published articles in English indexed in MEDLINE and the Cochrane Library (Issue 1, 2009), which includes the Economic Evaluation Database. Additional sources also were searched to identify unpublished varenicline studies, including conference abstracts. The search for varenicline studies was limited from 2006 to October 2009; searches for all other types of studies were limited from 1990 to October 2009. RESULTS: The search yielded a total of 20 relevant economic evaluations of varenicline. In addition, 37 reviews of economic evaluations in chronic obstructive pulmonary disease, non-small cell lung cancer and cardiovascular disease, as well as studies evaluating the impact of economic rewarding were considered in this review. From these identified economic evaluations, the incremental cost effectiveness ratios for varenicline ranged from dominance (more effective and cost saving) to ?18,582 per quality-adjusted life-year (including indirect costs). These estimates appeared substantially lower when compared with incremental cost-effectiveness ratios reported for secondary prevention of smoking-related diseases, which in some cases were as high as ?66,218 per quality adjusted life-year. CONCLUSIONS: Varenicline appears to be cost-effective from the perspective of both health care payers and employers, because of reduced health care consumption and costs. The cost-effectiveness of varenicline also compares favourably to that of interventions recommended for the treatment and prevention of smoking-related diseases. PMID- 21029269 TI - A review of the definitional criteria for chronic fatigue syndrome. AB - RATIONALE, AIMS AND OBJECTIVES: The research community has for more than three decades tried to unravel the diagnostic mystery that is Chronic Fatigue Syndrome (CFS). This has resulted in considerable amounts of time and money being invested in attempts aimed at establishing the aetiology and pathogenesis of CFS. All of this investment has produced evidence of an interesting variety of endocrine, immune, infectious, muscular and neurological abnormalities in CFS; however, the cause remains elusive. The absence of a known causative agent or diagnostic test for CFS has resulted in the development of a number of CFS case definitions. As such, the main objectives of this paper are to provide a critical review of the similarities and differences between the varying approaches to CFS case definition. The conflicts and controversies that have emerged as a result of the differing definitional criterion for CFS are highlighted and the potential impact on future research is identified. METHODS, RESULTS AND CONCLUSIONS: This paper presents a critical review of the most frequently used case definitions in CFS. There are currently five case definitions of CFS; however, the most prominent and widely used of these definitions is the 1994 Centre for Disease Control and Prevention Case Definitions. However, the pre-eminence of this definition over the others has never been substantiated and it has been widely criticized for its lack of specificity. Furthermore, none of the above case definitions have produced evidence to demonstrate their accuracy or precision at defining cases of CFS. A summary description of the symptom profile included in each of the case definitions is provided. The inconsistencies that have emerged in CFS research as a consequence of differing approaches to case definition are also highlighted and discussed. PMID- 21029270 TI - The factor structure of the SF-36 in adults with progressive neuromuscular disorders. AB - OBJECTIVE: Quality of life (QoL) is an important consideration in the care of patients with chronic neuromuscular disorder (NMD). The current study sought to determine the factor structure of the Medical Outcomes Study Short-Form 36 (SF 36) version 2 in patients with NMD to determine the appropriateness of using this instrument to assess QoL in this clinical population. METHODS: Confirmatory factor analyses were conducted on self-report SF-36 data from 245 individuals diagnosed with NMD. Six structural models of the SF-36 were evaluated against the participants' data. RESULTS: The underlying factor structure of the SF-36 in NMD was observed to be consistent with contemporary theoretical models of the instrument. However, the traditional measurement model of SF-36 performed comparatively poorly. CONCLUSION: The use of the SF-36 in individuals with NMD can be recommended when eight sub-scales are used and reported. However, the suggestion that the SF-36 can be usefully used as a two-sub-scale measure of physical health and mental health components in this clinical group was not supported because of model fit limitations. PMID- 21029271 TI - Development and evaluation of a checklist assessing communication skills of oncologists: the COM-ON-Checklist. AB - OBJECTIVES: Communication skills training (CST) has to be proven effective, and therefore reliable instruments to evaluate CST are required. Most instruments assessing medical consultations do not take individual aspects of CST into consideration. Such assessment tools should naturally also be closely associated with the communication skills taught to the participants. Thus, we developed a new instrument which evaluates the effects of specific CST. METHODS: DEVELOPMENT: Based on a literature review, we developed a checklist with questions ('items') which assess the behaviour of a doctor in a special doctor patient consultation (The COM-ON-Checklist, COM-ON = communication in oncology). First, we developed items for general communication skills that are a requirement of every doctor-patient consultation, and in addition to this, we developed items for specific situations which present a particular challenge for doctors in terms of communication skills, namely: the situation in which the doctor is required to discuss the shift from curative to palliative care, and the disclosure of information about clinical trials. For assessment, a 5-point rating scale with anchor points was used. EVALUATION: Blinded raters were trained to use the COM-ON Checklist. The intra-class correlation (ICC) was used to calculate the agreement between raters. RESULTS: The COM-ON-Checklist consists of two parts: the first part evaluates general communication skills; the second part evaluates content specific aspects of the consultation. The ICC ranged from 0.5 to 0.8, which demonstrates moderate to very good results of inter-rater reliability. DISCUSSION: The COM-ON-Checklist can be used to evaluate specific CST. It is also a feedback source for clinicians because it assesses their personal communication skills in different settings. In conclusion, the COM-ON-Checklist provides a reliable, structured method for assessing communication skills in oncological settings. PMID- 21029272 TI - Impact of practice recommendations on patient follow-up and cystic fibrosis centres' activity in France. AB - INTRODUCTION: The French cystic fibrosis (CF) practice recommendations were published at the end of 2002. They advise each patient to be checked up at least once every 3 months in a reference centre for cystic fibrosis. OBJECTIVE: To describe the activity of the four reference centres in the Rhone-Alpes area and the patients' follow-up. METHODS: All patients with cystic fibrosis consulting one of the four CF centres between 1996 and 2005 were retrospectively included. All outpatient visits were recorded and classified according to (i) patient and year; and (ii) month and year. The two series were assessed graphically to determine a transition threshold, that is, the 2 consecutive years between which practices differed the most. RESULTS: A total of 616 patients were included, representing 17 594 outpatient visits. The average number of visits per patient increased from 3.7 in 1996 to 5.0 in 2005, the graphical representation showed a sharp change between 2000 and 2001. Among patients with less than 4 visits in 2000, 88 of them visited a centre 4 times or more in 2001 (44%). The annual number of outpatient visits went from 1035 to 2420. The monthly average number of outpatient visits was 86 in 1996 and 202 in 2005. The graphical representation of activity also showed a sharp change from 2001. CONCLUSION: We showed that the implementation of guidelines occurred the year before its official publication. We also showed that the growth of this implementation was sharp rather than gradual. PMID- 21029273 TI - Implementing guidelines into clinical practice: what is the value? AB - RATIONALE AND OBJECTIVE: In budget-constrained health systems, decision makers need to consider both the costs and effects of introducing and actively implementing clinical guidance. We aim to demonstrate how, as an alternative to conventional methods, a total net benefit approach to economic evaluation can be used to inform decision making about guidelines and specific implementation strategies, like education or financial incentives. METHODS: Aside from providing more detail on the decision framework, we describe how to collect and analyse the relevant data for calculating the total net benefit of guideline use and the value of implementation. We illustrate the process of decision analysis for a stylized example on improving diabetes care in the UK. For the analysis, economic evidence on intensified glycemic control and that on audit and feedback to promote control is combined with information on diabetes practice. RESULTS: Our illustration demonstrates that the total net benefit of guideline use and the value of implementation can vary substantially, depending on the clinical intervention chosen, the health system being studied and the specific implementation strategies. This also holds for the threshold value for cost effectiveness, the duration of guideline usage or validity, the size of the patient population served, and the trends and ceiling rates in the implementation of clinical guidance. CONCLUSIONS: In comparison with conventional methods for health economic evaluation, a total net benefit approach allows for the explicit consideration of the current (or future) use of guidelines or guideline recommendations, the cost of implementation and the scope of clinical practice. Decisions made on the basis of the total net benefit of all plausible combinations of clinical guidance and implementation strategies provide optimal patient care and an efficient use of resources. PMID- 21029274 TI - Most like it but some don't--attitudes of vocational trainees in general practice towards evidence-based medicine. AB - RATIONALE AND OBJECTIVES: Vocational trainees in general practice are often confronted with new and unusual situations. The application of the principles and techniques of evidence-based medicine (EBM) could often be appropriate in these situations. We aimed to investigate attitudes towards EBM among doctors undergoing postgraduate training in general practice in Germany. In particular, we were interested in which aspects the answers of doctors with an overall negative attitude towards EBM differed from those with a positive attitude. METHODS: A total of 153 doctors participating in courses for postgraduate medical training in general practice were asked to fill in a questionnaire on attitudes towards EBM and relevance of clinical research. Answers of doctors with a negative attitude towards EBM (negative sum in the questions asking personal judgment on EBM) were compared with those of the remaining doctors. RESULTS: A total of 142 (93%) doctors returned the questionnaire and 121 responded to the questions on EBM (21 responded that they had not heard about EBM). On average, attitudes towards EBM were positive; however, nine doctors gave negative ratings. EBM-sceptics were similar regarding age, years working as doctors and working hours per week, but were more often male (P = 0.03). EBM-sceptics considered keeping up to date as important as non-sceptics but were significantly (P < 0.001) more negative regarding whether EBM is an important decision aid in one's personal work, whether it helps to identify the best clinical options and whether it constrains therapeutic freedom. CONCLUSION: Overall, doctors specializing in general practice in Germany have a quite positive attitude towards EBM. A small minority, however, seems to consider EBM a threat to their professional autonomy. PMID- 21029275 TI - Investigation of human sewage pollution and pathogen analysis at Florida Gulf coast beaches. AB - AIMS: Water quality at two Florida beaches was compared using faecal indicator bacteria measurements, microbial source tracking (MST) methods for detecting human source pollution and the assessment of pathogen presence. These values were also compared before and after remediation of wastewater infrastructure at one beach. METHODS AND RESULTS: Faecal coliforms, Escherichia coli and enterococci were enumerated in estuarine water and sediment samples. PCR assays for the human associated esp gene of Enterococcus faecium and human polyomaviruses (HPyVs) were used to detect human sewage. Culturable Salmonella and enteric viruses were also analysed. MST identified human sewage contamination at one beach, leading to repair of a sewer main and relocation of portable restrooms. Exceedances of Florida recreational water regulatory standards were significantly reduced after remediation (by 52% for faecal coliforms and 39% for enterococci), and the frequency of detection of MST markers decreased. Coxsackie virus B4 and HPyVs were codetected following a major sewage spill, but Salmonella was not detected during the study. CONCLUSIONS: These data indicate that infrastructure remediation significantly reduced pollution from human sewage at the impacted beach. SIGNIFICANCE AND IMPACT OF THE STUDY: A comprehensive microbial water quality study that can identify contamination sources through the use of MST markers and close collaboration with local/and state agencies can result in tangible actions to improve recreational water quality and safety. PMID- 21029276 TI - Identification and quantification of viable Bifidobacterium breve strain Yakult in human faeces by using strain-specific primers and propidium monoazide. AB - AIMS: To develop a quick and accurate PCR-based method to evaluate viable Bifidobacterium breve strain Yakult (BbrY) in human faeces. METHODS AND RESULTS: The number of BbrY in faeces was detected by using strain-specific quantitative real-time PCR (qPCR) derived from a randomly amplified polymorphic DNA analysis. And using propidium monoazide (PMA) treatment, which combined a DNA-intercalating dye for covalently linking DNA in dead cells and photoactivation, only viable BbrY in the faeces highly and significantly correlated with the number of viable BbrY added to faecal samples within the range of 10(5) -10(9) cells per g of faeces was enumerated. After 11 healthy subjects ingested 10.7 log CFU of BbrY daily for 10 days, 6.9 (+/- 1.5) log CFU g(-1) [mean (+/- SD)] of BbrY was detected in faeces by using strain-specific transgalactosylated oligosaccharide carbenicillin (T-CBPC) selective agar medium. Viable BbrY detected by qPCR with PMA treatment was 7.5 (+/- 1.0) log cells per g and the total number (viable and dead) of BbrY detected by qPCR without PMA treatment was 8.1 (+/- 0.8) log cells per g. CONCLUSIONS: Strain-specific qPCR with PMA treatment evaluated viable BbrY in faeces quickly and accurately. SIGNIFICANCE AND IMPACT OF THE STUDY: Combination of strain-specific qPCR and PMA treatment is useful for evaluating viable probiotics and its availability in humans. PMID- 21029278 TI - Using vignettes to explore judgements of patients about safety and quality of care: the role of outcome and relationship with the care provider. AB - BACKGROUND There is a growing body of evidence that safe outcomes and quality care are important to patients. For the patient, evaluations of safety and quality are made on the basis of the interpersonal interactions that they have with health professionals as well as the technical aspects of their care. OBJECTIVE In this study, we investigated the extent to which outcome of care (harm or not) and relationship (good or bad) with the care provider impact on the judgements of responsibility and blame as well as decisions about likelihood of making a complaint. METHOD Ninety-eight mothers made seven ratings of responsibility, blame and action in response to four hypothetical vignettes in a questionnaire. The vignettes described poor quality ante-natal care in which outcome and relationship with the health-care provider were systematically manipulated across different versions of the questionnaire. RESULTS Multivariate analyses showed that participants made significantly more negative ratings in response to vignettes describing a bad outcome and those that described a poor relationship with the health professional. However, whilst ratings of seriousness and likelihood of making a complaint were most influenced by the manipulation of outcome in the vignettes, judgements of blame and responsibility were most effected by the depiction of relationship with the health professional as good or bad. Moreover, for three of the four vignettes, relationship rather than outcome most strongly influenced overall ratings of care. DISCUSSION These findings are discussed in the context of theory and policy developments. PMID- 21029277 TI - Questioning context: a set of interdisciplinary questions for investigating contextual factors affecting health decision making. AB - OBJECTIVE: To combine insights from multiple disciplines into a set of questions that can be used to investigate contextual factors affecting health decision making. BACKGROUND: Decision-making processes and outcomes may be shaped by a range of non-medical or 'contextual' factors particular to an individual including social, economic, political, geographical and institutional conditions. Research concerning contextual factors occurs across many disciplines and theoretical domains, but few conceptual tools have attempted to integrate and translate this wide-ranging research for health decision-making purposes. METHODS: To formulate this tool we employed an iterative, collaborative process of scenario development and question generation. Five hypothetical health decision-making scenarios (preventative, screening, curative, supportive and palliative) were developed and used to generate a set of exploratory questions that aim to highlight potential contextual factors across a range of health decisions. FINDINGS: We present an exploratory tool consisting of questions organized into four thematic domains - Bodies, Technologies, Place and Work (BTPW) - articulating wide-ranging contextual factors relevant to health decision making. The BTPW tool encompasses health-related scholarship and research from a range of disciplines pertinent to health decision making, and identifies concrete points of intersection between its four thematic domains. Examples of the practical application of the questions are also provided. CONCLUSIONS: These exploratory questions provide an interdisciplinary toolkit for identifying the complex contextual factors affecting decision making. The set of questions comprised by the BTPW tool may be applied wholly or partially in the context of clinical practice, policy development and health-related research. PMID- 21029279 TI - Service user involvement in cancer care: the impact on service users. AB - BACKGROUND: Service user involvement is embedded in the United Kingdom's National Health Service, but knowledge about the impact of involvement on service users, such as the benefits and challenges of involvement, is scant. Our research addresses this gap. OBJECTIVE: To explore the personal impact of involvement on the lives of service users affected by cancer. DESIGN: We conducted eight focus groups with user groups supplemented by nine face-to-face interviews with involved individuals active at a local, regional and national level. Thematic analysis was conducted both independently and collectively. SETTING AND PARTICIPANTS: Sixty-four participants, engaged in involvement activities in cancer services, palliative care and research, were recruited across Great Britain. RESULTS: We identified three main themes: (i) 'Expectations and motivations for involvement'- the desire to improve services and the need for user groups to have a clear purpose, (ii) 'Positive aspects of involvement'- support provided by user groups and assistance to live well with cancer and (iii) 'Challenging aspects of involvement'- insensitivities and undervaluing of involvement by staff. CONCLUSIONS: This study identified that involvement has the capacity to produce varied and significant personal impacts for involved people. Involvement can be planned and implemented in ways that increase these impacts and that mediates challenges for those involved. Key aspects to increase positive impact for service users include the value service providers attach to involvement activities, the centrality with which involvement is embedded in providers' activities, and the capacity of involvement to influence policy, planning, service delivery, research and/or practice. PMID- 21029280 TI - The role of community representatives on health service committees: staff expectations vs. reality. AB - OBJECTIVE This paper examines staff views about legitimacy of different roles for community representatives sitting on health service committees as part of a formal Community Participation Program (CPP) in an Area Health Service (AHS) in Australia. DESIGN A cross-sectional survey using a self-completed questionnaire by staff on committees with community representation in the AHS in 2008. SETTING The study site has a population of approximately 1.4 million and covers 6000 km(2) . The population is ethnically and socio-economically diverse. RESULTS There are generally positive staff attitudes at this AHS for community participation as part of the CPP with positive impacts identified, including on service delivery and the conduct of health service meetings. Most saw community representatives having legitimate roles in representing the community, improving communication between the health service and the community and providing constructive feedback. However, staff expectations about the community's role on committees do not match the reality they say they observe and less than half the staff thought the community and health service agree on the role of community representatives. CONCLUSIONS As well as reviewing and enhancing training and support for representatives and staff as part of the CPP, there is a need to question staff expectations about community members who sit on health service committees and whether these expectations are shared by other key stakeholders, most notably the community representatives themselves. These expectations have implications for the CPP and for similar programs designed to engage community members on committees and working groups with health professionals. PMID- 21029281 TI - Clinicians' concerns about decision support interventions for patients facing breast cancer surgery options: understanding the challenge of implementing shared decision-making. AB - BACKGROUND: There is interest in interventions that provide support for patients facing challenging decisions, such as the choice between mastectomy and breast conservation surgery for breast cancer. However, it is difficult to implement these interventions. One potential source of resistance is the attitudes of clinicians. OBJECTIVE: To examine specialist breast clinicians' opinions about the provision of decision support interventions (DesIs) for patients. METHODS: As part of the development of a web-based DesI (BresDex), semi-structured interviews were conducted with specialist clinicians [breast surgeons, breast care nurses (BCNs) and oncologists] from four breast units in a UK region, and speciality national opinion leaders. Interviews were recorded, transcribed and analysed using the Framework approach. RESULTS: A majority of the 24 clinicians interviewed did not have a working knowledge of DesIs and were ambivalent or sceptical. Many expressed conflicting opinions: they noted the potential benefits, but at the same time expressed reservations about information overlap, overload and about content that they considered inappropriate. Many wanted access to DesIs to be always under clinical supervision. In particular, they were uncertain as regards how DeSIs could be tailored to individual patients' needs and also accommodate clinical practice variation. BCNs were particularly concerned that DesIs might induce patient anxiety and replace their role. CONCLUSIONS: The concept of providing interventions to support patients in decision-making tasks generated concern, defensiveness and scepticism. These attitudes will be a significant barrier. Implementation efforts will need to recognize and address these issues if these interventions are to become embedded in clinical practice. PMID- 21029282 TI - From awareness to involvement? A qualitative study of respiratory patients' awareness of health service change. AB - BACKGROUND Despite the policy rhetoric, patient involvement in health service decisions remains limited. Highlighted barriers include a concern that most patients are unable to see beyond personal aspects of their care in order to contribute meaningfully to health service development, and a perception that professionals do not welcome patient involvement. OBJECTIVES We aimed to explore respiratory patients' awareness of changes in local health service provision and provide insight into health professionals' attitudes to engaging patients. METHODS Nested within an ethnographic study of health service reconfiguration, we recruited 31 patients with a range of respiratory diseases from four case study areas in England and Wales. Data from telephone interviews, illness diaries and focus groups with patients, and interviews with health professionals and managers were transcribed and analysed using the Framework approach. RESULTS Participants were not only aware of trends in health service provision (e.g. emergence of new professional roles, shift from secondary to primary care) but interpreted changes in the light of local and national events. Despite this awareness, none of the patients was formally involved in service development, though some contributed to local voluntary groups. Professionals generally welcomed the need for patients' views to be heard. DISCUSSION AND CONCLUSIONS Our data give grounds for optimism. Patients are aware of and interested in a broad range of health-related issues. Professionals' motivation to involve patients in service development may be underestimated. Although practical obstacles remain, our findings should encourage the ongoing search for effective models of promoting patient engagement in health-care services. PMID- 21029283 TI - Exploring public perspectives on e-health: findings from two citizen juries. AB - BACKGROUND: Interest and investment in e-health continue to grow world-wide, but there remains relatively little engagement with the public on this subject, despite calls for more public involvement in health-care planning. DESIGN: This study used two modified citizen juries to explore barriers and facilitators to e health implementation and the priorities for future e-health research from the perspective of health service users and lay representatives. Citizen juries bring together a group of people to deliberate over a specific issue. They are given information and invited to 'cross-examine' witnesses during the process. RESULTS: Jurors were very keen for lay views to be included in e-health development and embraced the citizen jury approach. They agreed unanimously that e-health should be developed and thought it was in many ways inevitable. Although there was much enthusiasm for a health-care system which offered e-health as an option, there was as much concern about what it might mean for patients if implemented inappropriately. E-health was preferred as an enhancement rather than substitute for, existing services. Lack of universal access was seen as a potential barrier to implementation but problems such as lack of computer literacy were seen as a temporary issue. Participants emphasized that e-health research needed to demonstrate both clinical and economic benefits. CONCLUSION: There was broad support from the citizen juries for the development of e-health, although participants stressed that e-health should enhance, rather than substitute, face to-face services. One-day citizen juries proved a practical method of public engagement on this subject. PMID- 21029284 TI - The integration of citizens into a science/policy network in genetics: governance arrangements and asymmetry in expertise. AB - OBJECTIVE While there are increasing calls for public input into health research and policy, the actual obtaining of such input faces many challenges in practice. This article examines how a Canadian science/policy network in the field of genetics integrated citizens into its structure and then managed their participation. METHODS Our ethnographic case study covers a 5-year period (2003 08) and combines four data sources: observations of the network's meetings and informal activities, debriefing sessions with the network's leaders, semi structured interviews with network members (n = 20) and document analysis. RESULTS When setting up the network, the leaders wanted to include a range of perspectives (research, clinical and policy) to increase the relevance of their research production and knowledge-transfer activities. After 2 years of operation, the network's members agreed to also include citizens who were not knowledgeable in genetics and policy issues. As neither the structure nor the dynamics of the network were modified, the citizens very soon started to feel uncomfortable with their role. They doubted the relevance of their contribution, pointing to an asymmetry in knowledge between them and the expert members. There were significant tensions in the network's governance and the citizens' concerns during the process were not fully addressed. CONCLUSION The integration of citizens into transdisciplinary networks requires recognizing and addressing the asymmetry of expertise that underpins such a collaborative endeavour. It also requires understanding that citizens may feel uncomfortable adopting the pre defined role ascribed to them, may need a space of their own or may even withdraw if they feel being used. PMID- 21029285 TI - A relational perspective on autonomy for older adults residing in nursing homes. AB - AIM: To review critically the traditional concept of autonomy, propose an alternative relational interpretation of autonomy, and discuss how this would operate in identifying and addressing ethical issues that arise in the context of nursing home care for older adults. BACKGROUND: Respect for patient autonomy has been the cornerstone of clinical bioethics for several decades. Important though this principle is, there is debate on how to interpret the core concept of autonomy. We review the appeal of the traditional approach to autonomy in health care and then identify some of the difficulties with this conception. METHODS: We use philosophical methods to explain and discuss the traditional and relational conceptions of autonomy and we illuminate our discussion with examples of various contextual applications. CONCLUSION: We support the relational conception of autonomy as offering a richer, more contextualized understanding of autonomy which attends to the social, political and economic conditions that serve as background to an agent's deliberations. To illuminate these ideas, we discuss the situation of frail older adults who frequently find their autonomy limited not only by their medical conditions but also by cultural prejudices against the aged and by the conditions commonly found within the nursing homes in which many reside. We propose ways of improving the relational autonomy of this population. PMID- 21029286 TI - Reconciling the principle of patient autonomy with the practice of informed consent: decision-making about prognostication in uveal melanoma. AB - BACKGROUND: Influential views on how to protect patient autonomy in clinical care have been greatly shaped by rational and deliberative models of decision-making. OBJECTIVE: Our aim was to understand how the general principle of respecting autonomy can be reconciled with the local reality of obtaining consent in a clinical situation that precludes extended deliberation. METHOD: We interviewed 22 patients with intraocular melanoma who had been offered cytogenetic tumour typing to indicate whether the tumour was likely to shorten life considerably. They were interviewed before and/or up to 36 months after receiving cytogenetic results. Patients described their decision-making about the test and how they anticipated and used the results. Their accounts were analysed qualitatively, using inconsistencies at a descriptive level to guide interpretative analysis. RESULTS: Patients did not see a decision to be made. For those who accepted testing, their choice reflected trust of what the clinicians offered them. Patients anticipated that a good prognosis would be reassuring, but this response was not evident. Although they anticipated that a poor prognosis would enable end of-life planning, adverse results were interpreted hopefully. In general, the meaning of the test for patients was not separable from ongoing care. CONCLUSION: Models of decision-making and associated consent procedures that emphasize patients' active consideration of isolated decision-making opportunities are invalid for clinical situations such as this. Hence, responsibility for ensuring that a procedure protects patients' interests rests with practitioners who offer it and cannot be delegated to patients. PMID- 21029288 TI - The multiple facets of ubiquitination in the regulation of notch signaling pathway. AB - The Notch signaling pathway regulates numerous aspects of metazoan development and tissue renewal. Deregulation or loss of Notch signaling is associated with a wide range of human disorders from developmental syndromes to cancer. Notch receptors and their ligands are widely expressed throughout development, yet Notch activation is robustly controlled in a spatio-temporal manner. Within the past decades, genetic screens and biochemical approaches led to the identification of more than 10 E3 ubiquitin ligases and deubiquitinating enzymes implicated in the regulation of the Notch pathway. In this review, we highlight the recent studies in Notch signaling that reveal how ubiquitination of components of the Notch pathway, ranging from degradation to regulation of membrane trafficking, impacts on the developmental control of the signaling activities of both Notch receptors and their ligands. PMID- 21029287 TI - Drosophila rolling blackout displays lipase domain-dependent and -independent endocytic functions downstream of dynamin. AB - Drosophila temperature-sensitive rolling blackout (rbo(ts) ) mutants display a total block of endocytosis in non-neuronal cells and a weaker, partial defect at neuronal synapses. RBO is an integral plasma membrane protein and is predicted to be a serine esterase. To determine if lipase activity is required for RBO function, we mutated the catalytic serine 358 to alanine in the G-X-S-X-G active site, and assayed genomic rescue of rbo mutant non-neuronal and neuronal phenotypes. The rbo(S358A) mutant is unable to rescue rbo null 100% embryonic lethality, indicating that the lipase domain is critical for RBO essential function. Likewise, the rbo(S358A) mutant cannot provide any rescue of endocytic blockade in rbo(ts) Garland cells, showing that the lipase domain is indispensable for non-neuronal endocytosis. In contrast, rbo(ts) conditional paralysis, synaptic transmission block and synapse endocytic defects are all fully rescued by the rbo(S358A) mutant, showing that the RBO lipase domain is dispensable in neuronal contexts. We identified a synthetic lethal interaction between rbo(ts) and the well-characterized dynamin GTPase conditional shibire (shi(ts1)) mutant. In both non-neuronal cells and neuronal synapses, shi(ts1); rbo(ts) phenocopies shi(ts1) endocytic defects, indicating that dynamin and RBO act in the same pathway, with dynamin functioning upstream of RBO. We conclude that RBO possesses both lipase domain-dependent and scaffolding functions with differential requirements in non-neuronal versus neuronal endocytosis mechanisms downstream of dynamin GTPase activity. PMID- 21029289 TI - In vivo imaging of retrogradely transported synaptic vesicle proteins in Caenorhabditis elegans neurons. AB - Axonal transport is an essential process that carries cargoes in the anterograde direction to the synapse and in the retrograde direction back to the cell body. We have developed a novel in vivo method to exclusively mark and dynamically track retrogradely moving compartments carrying specific endogenous synaptic vesicle proteins in the Caenorhabditis elegans model. Our method is based on the uptake of a fluorescently labeled anti-green fluorescent protein (GFP) antibody delivered in an animal expressing the synaptic vesicle protein synaptobrevin 1::GFP in neurons. We show that this method largely labels retrogradely moving compartments. Very little labeling is observed upon blocking vesicle exocytosis or if the synapse is physically separated from the cell body. The extent of labeling is also dependent on the dyenin-dynactin complex. These data support the interpretation that the labeling of synaptobrevin-1::GFP largely occurs after vesicle fusion and the major labeling likely takes place at the synapse. Further, we observe that the retrograde compartment carrying synaptobrevin contains synaptotagmin but lacks the endosomal marker RAB-5. This labeling method is very general and can be readily adapted to any transmembrane protein on synaptic vesicles with a GFP tag inside the vesicle and can also be extended to other model systems. PMID- 21029290 TI - The Environmental Determinants of Diabetes in the Young (TEDDY) study: predictors of early study withdrawal among participants with no family history of type 1 diabetes. AB - OBJECTIVE: The Environmental Determinants of Diabetes in the Young (TEDDY) study seeks to identify environmental triggers of autoimmunity and type 1 diabetes mellitus (T1DM) in children at increased human-leukocyte-antigen conferred genetic risk for this disease. The objective of this study was to identify predictors of early withdrawal from TEDDY among families with no immediate family history of T1DM. METHOD: Logistic multiple regression was used to discriminate 2994 (83%) families currently active in the TEDDY study for >=1 yr from 763 (17%) families who withdrew in the first year. Data collected on the screening form at the time of the child's birth and from interview and questionnaire data obtained at the baby's first study visit (at <=4.5 months of age) were used. RESULTS: Significant and independent predictors of early withdrawal included country of residence, young maternal age, no father participation, and female gender of the study participant. Mothers of children who withdrew were more likely to report smoking during pregnancy, abstaining from alcohol, and reducing their work hours or not working at all during pregnancy. Mothers who withdrew were also more likely to underestimate their child's risk for T1DM and fail to respond to multiple items on the enrollment questionnaires or interview. Among mothers with accurate risk perceptions, those experiencing high anxiety about their child's risk were more likely to be early withdrawals. CONCLUSIONS: Identifying families at high risk for study withdrawal at the time of enrollment allows for targeting these families with individually tailored plans to help maintain their participation in the study. PMID- 21029291 TI - Cataract surgical outcomes, visual function and quality of life in four rural districts in Vietnam. AB - BACKGROUND: To evaluate cataract surgical outcomes in four rural districts of Ha Tinh Province, Vietnam. DESIGN: Cross-sectional study. PARTICIPANTS: Post cataract surgery patients sampled randomly from facilities in four rural districts of Ha Tinh Province >3 months after surgery. MAIN OUTCOME MEASURES: Postoperative visual acuity (VA), visual function and quality of life. RESULTS: Among 412 patients, the mean age was 74.5 +/- 9.4 years, 67% (276) were female, and 377 (91.5%) received intraocular lenses (IOL). Nearly two-thirds of patients had no postoperative visits after discharge. Postoperatively, more than 40% of eyes had presenting VA <6/18, while 20% remained <6/60. The mean self-reported visual function and quality of life for all patients were 68.7 +/- 23.8 and 73.8 +/- 21.6, respectively. Most patients (89.5%) were satisfied with surgery and the majority (94.4%) would recommend surgery to others. One-third of patients paid >=$US50 for surgery. In multiple regression modelling, older age (P < 0.01), intraoperative complications (P < 0.01) and failure to receive an IOL (P < 0.01) were associated with postoperative VA <6/60. CONCLUSION: Satisfaction with surgery was high, and many patients were willing to pay for their operations. Poor visual outcomes were common; however, and better surgical training is needed to reduce complications and their impact on visual outcomes. More intensive postoperative follow-up may also be beneficial. PMID- 21029292 TI - Vascular endothelial cells cultured from patients with cerebral or uncomplicated malaria exhibit differential reactivity to TNF. AB - Plasmodium falciparum malaria is a major cause of morbidity and mortality in African children, and factors that determine the development of uncomplicated (UM) versus cerebral malaria (CM) are not fully understood. We studied the ex vivo responsiveness of microvascular endothelial cells to pro-inflammatory stimulation and compared the findings between CM and UM patients. In patients with fatal disease we compared the properties of vascular endothelial cells cultured from brain tissue to those cultured from subcutaneous tissue, and found them to be very similar. We then isolated, purified and cultured primary endothelial cells from aspirated subcutaneous tissue of patients with CM (EC(CM) ) or UM (EC(UM) ) and confirmed the identity of the cells before analysis. Upon TNF stimulation in vitro, EC(CM) displayed a significantly higher capacity to upregulate ICAM-1, VCAM-1 and CD61 and to produce IL-6 and MCP-1 but not RANTES compared with EC(UM) . The shedding of endothelial microparticles, a recently described parameter of severity in CM, and the cellular level of activated caspase-3 were both significantly greater in EC(CM) than in EC(UM) . These data suggest that inter-individual differences in the endothelial inflammatory response to TNF may be an additional factor influencing the clinical course of malaria. PMID- 21029293 TI - What ails the beta-cell? PMID- 21029296 TI - Role of autophagy in beta-cell function and mass. AB - Type 2 diabetes (T2D) is characterized by decreased insulin secretion and action. Decreased insulin secretion results from a reduction in pancreatic beta-cell mass and/or function. Apoptosis, oxidative stress, mitochondrial dysfunction and endoplasmic reticulum (ER) stress responses including JNK activation have been suggested as mechanisms for the changes of pancreatic beta-cells in T2D; however, the underlying causes were not clearly elucidated. Autophagy is an intracellular process that plays crucial roles in cellular homeostasis through degradation and recycling of organelles. We have reported increased apoptosis and decreased proliferation of beta-cells with resultant reduction in the beta-cell mass in beta-cell-specific autophagy-deficient mice. Morphological analysis of beta-cells revealed accumulation of ubiquitinated proteins, swollen mitochondria and distended ER. Insulin secretory function ex vivo was also impaired. As a result, beta-cell-specific autophagy-deficient mice showed hypoinsulinaemia and hyperglycaemia. These results suggested that autophagy is necessary to maintain the structure, mass and function of pancreatic beta-cells. In addition, as autophagy may play a protective role against ER stress and rejuvenates organelle function, impaired autophagy may lead to mitochondrial dysfunction and ER stress, which have been implicated as potential causes of insulin resistance. Therefore, in addition to beta-cell homeostasis, dysregulated autophagy may possibly be involved in diverse aspects of the pathogenesis of diabetes. PMID- 21029294 TI - Autophagic pathways and metabolic stress. AB - Autophagy is an essential intracellular process that mediates degradation of intracellular proteins and organelles in lysosomes. Autophagy was initially identified for its role as alternative source of energy when nutrients are scarce but, in recent years, a previously unknown role for this degradative pathway in the cellular response to stress has gained considerable attention. In this review, we focus on the novel findings linking autophagic function with metabolic stress resulting either from proteins or lipids. Proper autophagic activity is required in the cellular defense against proteotoxicity arising in the cytosol and also in the endoplasmic reticulum, where a vast amount of proteins are synthesized and folded. In addition, autophagy contributes to mobilization of intracellular lipid stores and may be central to lipid metabolism in certain cellular conditions. In this review, we focus on the interrelation between autophagy and different types of metabolic stress, specifically the stress resulting from the presence of misbehaving proteins within the cytosol or in the endoplasmic reticulum and the stress following a lipogenic challenge. We also comment on the consequences that chronic exposure to these metabolic stressors could have on autophagic function and on how this effect may underlie the basis of some common metabolic disorders. PMID- 21029295 TI - The role of autophagy in beta-cell lipotoxicity and type 2 diabetes. AB - Autophagy, a ubiquitous catabolic pathway involved in both cell survival and cell death, has been implicated in many age-associated diseases. Recent findings have shown autophagy to be crucial for proper insulin secretion and beta-cell viability. Transgenic mice lacking autophagy in their beta-cells showed decreased beta-cell mass and suppressed glucose-stimulated insulin secretion. Several studies showed that stress can stimulate autophagy in beta-cells: the number of autophagosomes is increased in different in vivo models for diabetes, such as db/db mice, mice fed high-fat diet, pdx-1 knockout mice, as well as in in vitro models of glucotoxicity and lipotoxicity. Pharmacological and molecular inhibition of autophagy increases the susceptibility to cell stress, suggesting that autophagy protects against diabetes-relevant stresses. Recent findings, however, question these conclusions. Pancreases of diabetics and beta-cells exposed to fatty acids show accumulation of abnormal autophagosome morphology and suppression of lysosomal gene expression suggesting impairment in autophagic turnover. In this review we attempt to give an overview of the data generated by others and by us in view of the possible role of autophagy in diabetes, a role which depending on the conditions, could be beneficial or detrimental in coping with stress. PMID- 21029297 TI - The unfolded protein response and translation attenuation: a modelling approach. AB - Unfolded protein response (UPR) is a stress response to increased levels of unfolded proteins in the endoplasmic reticulum (ER). To deal with this stress, all eukaryotic cells share a well-conserved strategy--the upregulation of chaperons and proteases to facilitate protein folding and to degrade the misfolded proteins. For metazoans, however, an additional and seemingly redundant strategy has been evolved--translation attenuation (TA) of proteins targeted to the ER via the protein kinase PERK pathway. PERK is essential in secretory cells, such as the pancreatic beta-cells, but not in non-secretory cell types. We have recently developed a mathematical model of UPR, focusing on the interplay and synergy between the TA arm and the conserved Ire1 arm of the UPR. The model showed that the TA mechanism is beneficial in highly fluctuating environment, for example, in the case where the ER stress changes frequently. Under highly variable levels of ER stress, tight regulation of the ER load by TA avoids excess amount of chaperons and proteases being produced. The model also showed that TA is of greater importance when there is a large flux of proteins through the ER. In this study, we further expand our model to investigate different types of ER stress and different temporal profiles of the stress. We found that TA is more desirable in dealing with the translation stress, for example, prolonged stimulation of proinsulin biosynthesis, than the chemical stress. PMID- 21029298 TI - Molecular chaperones and substrate ubiquitination control the efficiency of endoplasmic reticulum-associated degradation. AB - The endoplasmic reticulum (ER) must contend with a large protein flux, which is especially notable in cells dedicated to secreting hormone-regulated gene products. Because of the complexity of the protein folding pathway and the potential for genetic or stochastic errors, a significant percentage of these nascent secreted proteins fail to acquire their native conformations. If these species cannot be cleared from the ER, they may aggregate, which leads to cell death. To lessen the effects of potentially toxic polypeptides, aberrant ER proteins are destroyed via a process known as ER-associated degradation (ERAD). ERAD substrates are selected by molecular chaperones and chaperone-like proteins, and prior to degradation most substrates are ubiquitin-modified. Together with the unfolded protein response, the ERAD pathway is a critical component of the protein quality control machinery in the ER. Although emerging data continue to link ERAD with human diseases, most of our knowledge of this pathway arose from studies using a model eukaryote, the yeast Saccharomyces cerevisiae. In this review, we will summarize the discoveries that led to our current understanding of this pathway, focusing primarily on experiments in yeast. We will also indicate links between ERAD and disease and emphasize future research avenues. PMID- 21029299 TI - From antibodies to adiponectin: role of ERp44 in sizing and timing protein secretion. AB - A large fraction of the proteome is synthesized and folded in the endoplasmic reticulum (ER), a multifunctional compartment also playing pivotal roles in Ca(2+) storage, redox homeostasis and signalling. From the ER, secretory proteins begin their journey towards their final destinations, the organelles of the exocytic and endocytic compartments, the plasma membrane or the extracellular space. Fidelity of protein-based intracellular communication is guaranteed by quality control (QC) mechanisms located at the ER-Golgi interface, which restrict forward transport to native proteins. QC is used also to time or shape the secretome. Furthermore, professional secretory cells face a problem of quantity, as well as quality of their protein products. This essay summarizes recent findings that identify ERp44 as a key regulator of protein secretion, Ca(2+) signalling and redox regulation. PMID- 21029300 TI - The endoplasmic reticulum stress response in the pancreatic beta-cell. AB - Eukaryotic cells respond to stress in the endoplasmic reticulum (ER) resulting from insufficient protein folding capacity or altered ER homeostasis by activating the unfolded protein response (UPR). In mammalian cells the UPR is mediated by at least three ER-localized sensors/transducers, and the cellular response and susceptibility to ER stress is likely to be cell-type specific to some degree. Here, we review the response of pancreatic beta-cells or islets to ER stress induced by pharmacological agents, misfolded insulin expression, excessive nutrient exposure and in animal models of type 2 diabetes. This review highlights the particular importance of PERK-mediated translational control and the transcriptional response in pancreatic beta-cells and how these relate to the highly specialized function of beta-cells, namely glucose-regulated insulin secretion and production. We examine how chronic ER stress may prematurely 'age' the beta-cell or cause its genetic reprogramming to either reduce its ability to mount a cell survival response to ER stress, or impair normal function. Both could contribute to beta-cell failure in diabetes. We also explore the therapeutic potential of targeting the UPR to preserve beta-cell function. PMID- 21029302 TI - Glucose regulation of beta-cell stress in type 2 diabetes. AB - In type 2 diabetes, the beta-cell is exposed to chronic hyperglycaemia, which increases its metabolic activity, with excess generation of reactive oxygen species (ROS) as a consequence. ROS accumulation induces both oxidative and endoplasmic reticulum (ER) stress, which may lead to beta-cell dysfunction and apoptosis. Recent data suggest that oxidative and ER stress are interconnected, although the mechanisms involved in nutrient regulation of the different stress pathways are dissimilar. Several components of the oxidative and ER stress machineries have important roles in the physiological response to glucose and are thus necessary for normal beta-cell function. Glucose stimulates signalling pathways that provide crucial messages for beta-cell adaptation to metabolic stress; however, the same pathways may eventually lead to apoptosis. Dynamic, temporally fluctuating activation of stress signalling is probably required for the maintenance of beta-cell survival, whereas its persistent activation results in beta-cell dysfunction and apoptosis. Thus, stress signalling is a 'double edged sword' that may promote adaptation or apoptosis according to the balance between the divergent outputs of the various pathways. Developing new strategies for beta-cell protection based on inhibition of oxidative and/or ER stress requires comprehensive understanding of the switch from beta-cell adaptation to beta-cell apoptosis under conditions of metabolic stress, such as occurs under hyperglycaemic conditions. PMID- 21029301 TI - A switch from life to death in endoplasmic reticulum stressed beta-cells. AB - beta-Cell death is an important pathogenic component of both type 1 and type 2 diabetes. Recent findings indicate that cell signalling pathways emanating from the endoplasmic reticulum (ER) play an important role in the regulation of beta cell death during the progression of diabetes. Homeostasis within the ER must be maintained to produce properly folded secretory proteins, such as insulin, in response to the body's need for them. However, the sensitive protein-folding environment in the ER can be perturbed by genetic and environmental factors leading to ER stress. To counteract ER stress, beta-cells activate cell signalling pathways termed the unfolded protein response (UPR). The UPR functions as a binary switch between life and death, regulating both survival and death effectors. The outcome of this switch depends on the nature of the ER stress condition, the regulation of UPR activation and the expression and activation of survival and death components. This review discusses the mechanisms and the components in this switch and highlights the roles of this UPR's balancing act between life and death in beta-cells. PMID- 21029303 TI - Causes and cures for endoplasmic reticulum stress in lipotoxic beta-cell dysfunction. AB - Pancreatic beta-cell dysfunction is central to the pathogenesis of type 2 diabetes, and the loss of functional beta-cell mass in type 2 diabetes is at least in part secondary to increased beta-cell apoptosis. Accumulating evidence suggests that endoplasmic reticulum (ER) stress is present in beta-cells in type 2 diabetes. Free fatty acids (FFAs) cause ER stress and are putative mediators of beta-cell dysfunction and death. In this review, we discuss the molecular mechanisms underlying ER stress induced by saturated and unsaturated FFAs. Oleate and palmitate trigger ER stress through ER Ca(2+) depletion and build-up of unfolded proteins in the secretory pathway. Saturated and unsaturated FFAs elicit a differential signal transduction in the three branches of the ER stress response, resulting in different survival/apoptosis outcomes. The protection of beta-cells against FFAs through the interference with ER stress signalling has opened novel therapeutic perspectives for type 2 diabetes. Chemical chaperones, salubrinal and glucagon-like peptide-1 (GLP-1) analogues have been used to protect beta-cells from lipotoxic ER stress. Importantly, the pro- and antiapoptotic effects of these compounds are cell and context dependent. PMID- 21029304 TI - Hepatic steatosis: a role for de novo lipogenesis and the transcription factor SREBP-1c. AB - Steatosis is an accumulation of triglycerides in the liver. Although an excessive availability of plasma fatty acids is an important determinant of steatosis, lipid synthesis from glucose (lipogenesis) is now also considered as an important contributing factor. Lipogenesis is an insulin- and glucose-dependent process that is under the control of specific transcription factors, sterol regulatory element binding protein 1c (SREBP-1c), activated by insulin and carbohydrate response element binding protein (ChREBP) activated by glucose. Insulin induces the maturation of SREBP-1c by a proteolytic mechanism initiated in the endoplasmic reticulum (ER). SREBP-1c in turn activates glycolytic gene expression, allowing glucose metabolism, and lipogenic genes in conjunction with ChREBP. Lipogenesis activation in the liver of obese markedly insulin-resistant steatotic rodents is then paradoxical. Recent data suggest that the activation of SREBP-1c and thus of lipogenesis is secondary in the steatotic liver to an ER stress. The ER stress activates the cleavage of SREBP-1c independent of insulin, thus explaining the paradoxical stimulation of lipogenesis in an insulin resistant liver. Inhibition of the ER stress in obese rodents decreases SREBP-1c activation and lipogenesis and improves markedly hepatic steatosis and insulin sensitivity. ER is thus a new partner in steatosis and metabolic syndrome which is worth considering as a potential therapeutic target. PMID- 21029305 TI - A link between endoplasmic reticulum stress-induced beta-cell apoptosis and the group VIA Ca2+-independent phospholipase A2 (iPLA2beta). AB - Endoplasmic reticulum (ER) stress is becoming recognized as an important contributing factor in various diseases, including diabetes mellitus. Prolonged ER stress can cause beta-cell apoptosis; however, the underlying mechanism(s) that contribute to this process are not well understood. Early reports suggested that arachidonic acid metabolites and a Ca(2+)-independent phospholipase A(2) (iPLA(2)) activity play a role in beta-cell apoptosis. The PLA(2) family of enzymes catalyse the hydrolysis of the sn-2 substituent (i.e. arachidonic acid) of membrane phospholipids. In light of our findings that the pancreatic islet beta-cells are enriched in arachidonate-containing phospholipids and express the group VIA iPLA(2)beta, we considered the possibility that iPLA(2)beta participates in ER stress-induced beta-cell apoptosis. Our work revealed a novel mechanism, involving ceramide generation and triggering of mitochondrial abnormalities, by which iPLA(2)beta participates in the beta-cell apoptosis process. Here, we review our evidence linking ER stress, beta-cell apoptosis and iPLA(2)beta. Continued studies in this area will increase our understanding of the contribution of iPLA(2)beta to the evolution of diabetes mellitus and will further our knowledge of factors that influence beta-cell health in diabetes mellitus and identify potential targets for future therapeutic interventions to prevent beta-cell death. PMID- 21029307 TI - Restoring endoplasmic reticulum function by chemical chaperones: an emerging therapeutic approach for metabolic diseases. AB - The endoplasmic reticulum (ER) is a eukaryotic organelle that plays important roles in protein synthesis, folding and trafficking, calcium homoeostasis and lipid and steroid synthesis. It is the major protein synthesis compartment for secreted, plasma membrane and organelle proteins. Perturbations of ER homeostasis such as the accumulation of unfolded or misfolded proteins cause ER stress. To alleviate this stress, ER triggers an evolutionarily conserved signalling cascade called the unfolded protein response (UPR). As an initial response, the UPR aims at adapting and restoring ER function by translational attenuation, upregulation of ER chaperones and degradation of unfolded proteins. However, if the ER function is severely impaired because of excessive or prolonged exposure to stress, then the inflicted cells may undergo programmed cell death. During ER stress, unstable or partially folded mutant proteins are prevented from trafficking to their proper subcellular localizations and usually rapidly degraded. The small molecules named chemical chaperones help to stabilize these mutant proteins and facilitate their folding and proper trafficking from the ER to their final destinations. Because increasing number of studies suggest that ER stress is involved in a number of disease pathogenesis including neurodegenerative diseases, cancer, obesity, diabetes and atherosclerosis, promoting ER folding capacity through chemical chaperones emerges as a novel therapeutic approach. In this review, we provide insight into the many important functions of chemical chaperones during ER stress, their impact on the ER-stress related pathologies and their potential as a new drug targets, especially in the context of metabolic disorders. PMID- 21029306 TI - The unfolded protein response is required to maintain the integrity of the endoplasmic reticulum, prevent oxidative stress and preserve differentiation in beta-cells. AB - Diabetes is an epidemic of worldwide proportions caused by beta-cell failure. Nutrient fluctuations and insulin resistance drive beta-cells to synthesize insulin beyond their capacity for protein folding and secretion and thereby activate the unfolded protein response (UPR), an adaptive signalling pathway to promote cell survival upon accumulation of unfolded protein in the endoplasmic reticulum (ER). Protein kinase-like endoplasmic reticulum kinase (PERK) signals one component of the UPR through phosphorylation of eukaryotic initiation factor 2 on the alpha-subunit (eIF2alpha) to attenuate protein synthesis, thereby reducing the biosynthetic burden. beta-Cells uniquely require PERK-mediated phosphorylation of eIF2alpha to preserve cell function. Unabated protein synthesis in beta-cells is sufficient to initiate a cascade of events, including oxidative stress, that are characteristic of beta-cell failure observed in type 2 diabetes. In contrast to acute adaptive UPR activation, chronic activation increases expression of the proapoptotic transcription factor CAAT/enhancer binding protein homologous protein (CHOP). Chop deletion in insulin-resistant mice profoundly increases beta-cell mass and prevents beta-cell failure to forestall the progression of diabetes. The findings suggest an unprecedented link by which protein synthesis and/or misfolding in the ER causes oxidative stress and should encourage the development of novel strategies to treat diabetes. PMID- 21029308 TI - Redox compartmentalization and cellular stress. AB - Mammalian cells are highly organized to optimize function. For instance, oxidative energy-producing processes in mitochondria are sequestered away from plasma membrane redox signalling complexes and also from nuclear DNA, which is subject to oxidant-induced mutation. Proteins are unique among macromolecules in having reversible oxidizable elements, 'sulphur switches', which support dynamic regulation of structure and function. Accumulating evidence shows that redox signalling and control systems are maintained under kinetically limited steady states, which are highly displaced from redox equilibrium and distinct among organelles. Mitochondria are most reducing and susceptible to oxidation under stressed conditions, while nuclei are also reducing but relatively resistant to oxidation. Within compartments, the glutathione and thioredoxin systems serve parallel and non-redundant functions to maintain the dynamic redox balance of subsets of protein cysteines, which function in redox signalling and control. This organization allows cells to be poised to respond to cell stress but also creates sites of vulnerability. Importantly, disruption of redox organization is a common basis for disease. Research tools are becoming available to elucidate details of subcellular redox organization, and this development highlights an opportunity for a new generation of targeted antioxidants to enhance and restore redox signalling and control in disease prevention. PMID- 21029310 TI - Mitochondrial uncoupling protein 2 in pancreatic beta-cells. AB - Pancreatic beta-cells have remarkable bioenergetics in which increased glucose supply upregulates the cytosolic ATP/ADP ratio and increases insulin secretion. This arrangement allows glucose-stimulated insulin secretion (GSIS) to be regulated by the coupling efficiency of oxidative phosphorylation. Uncoupling protein 2 (UCP2) modulates coupling efficiency and may regulate GSIS. Initial measurements of GSIS and glucose tolerance in Ucp2(-/-) mice supported this model, but recent studies show confounding effects of genetic background. Importantly, however, the enhancement of GSIS is robustly recapitulated with acute UCP2 knockdown in INS-1E insulinoma cells. UCP2 protein level in these cells is dynamically regulated, over at least a fourfold concentration range, by rapid proteolysis (half-life less than 1 h) opposing regulated gene transcription and mRNA translation. Degradation is catalysed by the cytosolic proteasome in an unprecedented pathway that is currently known to act only on UCP2 and UCP3. Evidence for proteasomal turnover of UCP2 includes sensitivity of degradation to classic proteasome inhibitors in cells, and reconstitution of degradation in vitro in mitochondria incubated with ubiquitin and the cytosolic 26S proteasome. These dynamic changes in UCP2 content may provide a fine level of control over GSIS in beta-cells. PMID- 21029309 TI - Impact of nitric oxide on metabolism in health and age-related disease. AB - Nitric oxide (NO) serves as a messenger molecule in a variety of physiological systems and also converts into toxic radical species that can damage cells through a process known as nitrosative stress. While the physiological roles of NO in blood vessel dilation, the nervous system and the immune system are well established, recent studies have begun to investigate the role of NO in metabolism and energy expenditure through modulation of mitochondria. NO appears to stimulate mitochondrial biogenesis in certain situations through activation of proteins such as peroxisome proliferator-activated receptor gamma (PPARgamma) co activator 1alpha (PGC1-alpha). Because of this link between NO and mitochondrial biogenesis, the role of NO in certain aspects of metabolism, including exercise response, obesity, fat cell differentiation and caloric restriction, are the subject of increasing investigation. In addition to its role in mitochondrial biogenesis, NO also stimulates mitochondrial fragmentation, which can be caused by too much mitochondrial fission or inhibition of mitochondrial fusion and can result in bioenergetic failure. While the contribution of NO-mediated mitochondrial fragmentation to neurodegenerative diseases seems clear, the mechanisms by which NO causes fragmentation are uncertain and controversial. In this review, we discuss the role of NO in manipulation of mitochondrial biogenesis and dynamics and how these events contribute to human health- and age related disease. PMID- 21029311 TI - Reactive oxygen species and uncoupling protein 2 in pancreatic beta-cell function. AB - Growing evidence indicates that reactive oxygen species (ROS) are not just deleterious by-products of respiratory metabolism in mitochondria, but can be essential elements for many biological responses, including in pancreatic beta cells. ROS can be a 'second-messenger signal' in response to hormone/receptor activation that serves as part of the 'code' to trigger the ultimate biological response, or it can be a 'protective signal' to increase the levels of antioxidant enzymes and small molecules to scavenge ROS, thus restoring cellular redox homeostasis. In pancreatic beta-cells evidence is emerging that acute and transient glucose-dependent ROS contributes to normal glucose-stimulated insulin secretion (GSIS). However, chronic and persistent elevation of ROS, resulting from inflammation or excessive metabolic fuels such as glucose and fatty acids, may elevate antioxidant enzymes such that they blunt ROS and redox signalling, thus impairing beta-cell function. An interesting mitochondrial protein whose main function appears to be the control of ROS is uncoupling protein 2 (UCP2). Despite continuing investigation of the exact mechanism by which UCP2 is 'activated', it is clear that UCP2 levels and/or activity impact the efficacy of GSIS in pancreatic islets. This review will focus on the paradoxical roles of ROS in pancreatic beta-cell function and the regulatory role of UCP2 in ROS signalling and GSIS. PMID- 21029312 TI - Role of metabolically generated reactive oxygen species for lipotoxicity in pancreatic beta-cells. AB - Chronically elevated concentrations of non-esterified fatty acids (NEFAs) in type 2 diabetes may be involved in beta-cell dysfunction and apoptosis. It has been shown that long-chain saturated NEFAs exhibit a strong cytotoxic effect upon insulin-producing cells, while short-chain as well as unsaturated NEFAs are well tolerated. Moreover, long-chain unsaturated NEFAs counteract the toxicity of palmitic acid. Reactive oxygen species (ROS) formation and gene expression analyses together with viability assays in different beta-cell lines showed that the G-protein-coupled receptors 40 and 120 do not mediate lipotoxicity. This is independent from the role, which these receptors, specifically GPR40, play in the potentiation of glucose-induced insulin secretion by saturated and unsaturated long-chain NEFAs. Long-chain NEFAs are not only metabolized in the mitochondria but also in peroxisomes. In contrast to mitochondrial beta-oxidation, the acyl coenzyme A (CoA) oxidases in the peroxisomes form hydrogen peroxide and not reducing equivalents. As beta-cells almost completely lack catalase, they are exceptionally vulnerable to hydrogen peroxide generated in peroxisomes. ROS generation in the respiratory chain is less important because overexpression of catalase and superoxide dismutase in the mitochondria do not provide protection. Thus, peroxisomally generated hydrogen peroxide is the likely ROS that causes pancreatic beta-cell dysfunction and ultimately beta-cell death. PMID- 21029313 TI - The hypoxia response pathway and beta-cell function. AB - beta-cells sense glucose and secrete appropriate amounts of insulin by coupling glucose uptake and glycolysis with quantitative ATP production via mitochondrial oxidative pathways. Therefore, oxidative phosphorylation is essential for normal beta-cell function. Multiple cell types adapt to hypoxia by inducing a transcriptional programme coordinated by the transcription factor hypoxia inducible factor (HIF). HIF activity is regulated by the von Hippel-Lindau (Vhl) protein, which targets the HIFalpha subunit for proteasomal degradation in the presence of oxygen. Several recent studies have shown that Vhl deletion in beta cells results in Hif1alpha activation, impaired glucose-stimulated insulin secretion (GSIS) and glucose intolerance. This was found to be because of alterations in beta-cell gene expression inducing a switch from aerobic glucose metabolism to anaerobic glycolysis, thus disrupting the GSIS triggering pathway. Situations in which islets may become hypoxic are discussed, in particular islet transplantation which has been reported to cause islet hypoxia because of an inadequate blood supply post-transplant. Aside from this principal role for HIF in negatively regulating beta-cell glucose sensing, other aspects of hypoxia signalling are discussed including beta-cell differentiation, development and vascularization. In conclusion, recent studies clearly show that hypoxia response mechanisms can negatively impact on glucose sensing mechanisms in the beta-cell and this has the potential to impair beta-cell function in a number of physiological and clinical situations. PMID- 21029314 TI - Long-term outcomes of a randomized controlled trial comparing thermochemotherapy with mitomycin-C alone as adjuvant treatment for non-muscle-invasive bladder cancer (NMIBC). AB - OBJECTIVE: * To present long-term efficacy data of intravesical thermochemotherapy vs chemotherapy alone with mitomycin-C (MMC) randomly administered to patients with non-muscle-invasive bladder cancer (NMIBC) as an adjuvant treatment after complete transurethral resection. PATIENTS AND METHODS: * In all, 83 patients with intermediate-/high-risk NMIBC, following complete transurethral resection, were randomly assigned to receive either intravesical thermochemotherapy by means of Synergo(r) (Medical Enterprises, Amsterdam, The Netherlands) or intravesical chemotherapy alone, for prophylaxis of tumour recurrence. * Two doses of MMC (20 mg dissolved in 50 mL distilled water administered throughout two consecutive sessions) was used as the chemotherapeutic agent in both arms. * In all, 75 patients completed the original study (35 of 42 in the treatment arm, 40 of 41 in the control arm), whose results at minimum 2-year follow-up have already been published. * Recently, the files of these patients have been updated for long-term outcome definition. Data on general health, follow-up examinations, tumour relapse or progression, and cause of death were collected and analysed. RESULTS: * Updated complete data collection was available for 65/75 (87%) of the original patients. * The median follow-up for tumour-free patients was 91 months. The 10-year disease-free survival rate for thermochemotherapy and chemotherapy alone were 53% and 15%, respectively (P < 0.001). * An intent-to-treat analysis performed to overcome the potential bias introduced by the asymmetrical discontinuation rate still showed a significant advantage of the active treatment over the control treatment. Bladder preservation rates for thermochemotherapy and chemotherapy alone were 86% and 79%, respectively. CONCLUSION: * This is the first analysis of long-term follow up of patients treated with intravesical thermochemotherapy. The high rate (53%) of patients who were tumour-free 10 years after treatment completion, as well as the high rate (86%) of bladder preservation, confirms the efficacy of this adjuvant approach for NMIBC at long-term follow-up, even in patients with multiple tumours. PMID- 21029315 TI - Comparison of laparoscopic versus open radical nephrectomy for large renal tumors: a retrospective analysis of multi-center results. AB - OBJECTIVE: * To assess the feasibility and oncologic efficacy of laparoscopic radical nephrectomy (LRN) compared with open radical nephrectomy (ORN) in patients with large renal cell carcinomas (RCCs) > 7 cm in size. PATIENTS AND METHODS: * We analysed the data from 255 patients who underwent radical nephrectomies at 26 institutions in Korea between January 2000 and December 2007 for RCCs > 7 cm in size. * Eighty-eight patients who underwent LRNs were compared with 167 patients who underwent ORNs. The patients with tumor thrombi in the renal vein or IVC, and lymph node or distant metastases were excluded. * We compared the operative time, estimated blood loss, complication rates, and 2-year overall and disease-free survival rates between the LRN and ORN groups. RESULTS: * The median duration of postoperative follow-up was 19 months for the LRN group and 25.8 months for the ORN group. * The operative time was significantly longer in the LRN group than in the ORN group (241.5 +/- 74.8 min vs 202.7 +/- 69.6 min, P < 0.001) and blood loss was significantly lower in the LRN group than in the ORN group (439.8 +/- 326.8 mL vs 604.4 +/- 531.4 mL, P = 0.006). * No statistically significant difference was found in complication rates, the 2-year overall (92.7% vs 94%, P = 0.586) and disease-specific (90.1% vs 93.7%, P = 0.314) survival rates between the LRN and ORN groups. CONCLUSIONS: * Despite the longer operative time, LRN was an effective and less invasive treatment option for clinical T2 renal tumors. It achieved a degree of cancer control similar to that obtained with ORN. PMID- 21029316 TI - Content validation of a novel robotic surgical simulator. AB - OBJECTIVE: * To assess the content validity of an early prototype robotic simulator. Minimally invasive surgery poses challenges for training future surgeons. The Robotic Surgical Simulator (RoSS) is a novel virtual reality simulator for the da Vinci Surgical System. PATIENTS AND METHODS: * Participants attending the 2010 International Robotic Urology Symposium were invited to experience RoSS. Afterwards, participants completed a survey regarding the appropriateness of the simulator as a teaching tool. RESULTS: * Forty-two subjects including surgeons experienced with robotics (n= 31) and novices (n= 11) participated in this study. * Eighty per cent of the entire cohort had an average of 4 years of experience with robot-assisted surgery. * Eleven (26%) novices lacked independent robot-assisted experience. The expert group comprised 17 (41%) surgeons averaging 881 (160-2200) robot-assisted cases. Experts rated the 'clutch control' virtual simulation task as a good (71%) or excellent (29%) teaching tool. * Seventy-eight per cent rated the 'ball place' task as good or excellent but 22% rated it as poor. * Twenty-seven per cent rated the 'needle removal' task as an excellent teaching tool, 60% rated it good and 13% rated it poor. * Ninety one per cent rated the 'fourth arm tissue removal' task as good or excellent. * Ninety-four per cent responded that RoSS would be useful for training purposes. * Eighty-eight per cent felt that RoSS would be an appropriate training and testing format before operating room experience for residents. * Seventy-nine per cent indicated that RoSS could be used for privileging or certifying in robotic surgery. CONCLUSION: * Results based on expert evaluation of RoSS as a teaching modality illustrate that RoSS has appropriate content validity. PMID- 21029318 TI - Expression of sweet pepper Hrap gene in banana enhances resistance to Xanthomonas campestris pv. musacearum. AB - Banana Xanthomonas wilt (BXW), caused by the bacterium Xanthomonas campestris pv. musacearum, is the most devastating disease of banana in the Great Lakes region of Africa. The pathogen's rapid spread has threatened the livelihood of millions of Africans who rely on banana fruit for food security and income. The disease is very destructive, infecting all banana varieties, including both East African Highland bananas and exotic types of banana. In the absence of natural host plant resistance among banana cultivars, the constitutive expression of the hypersensitivity response-assisting protein (Hrap) gene from sweet pepper (Capsicum annuum) was evaluated for its ability to confer resistance to BXW. Transgenic lines expressing the Hrap gene under the regulation of the constitutive CaMV35S promoter were generated using embryogenic cell suspensions of two banana cultivars: 'Sukali Ndiizi' and 'Mpologoma'. These lines were characterized by molecular analysis, and were challenged with Xanthomonas campestris pv. musacearum to analyse the efficacy of the Hrap gene against BXW. The majority of transgenic lines (six of eight) expressing Hrap did not show any symptoms of infection after artificial inoculation of potted plants in the screenhouse, whereas control nontransgenic plants showed severe symptoms resulting in complete wilting. This study demonstrates that the constitutive expression of the sweet pepper Hrap gene in banana results in enhanced resistance to BXW. We describe the development of transgenic banana varieties resistant to BXW, which will boost the arsenal available to fight this epidemic disease and save livelihoods in the Great Lakes region of East and Central Africa. PMID- 21029317 TI - Adding amikacin to fluoroquinolone-based antimicrobial prophylaxis reduces prostate biopsy infection rates. AB - OBJECTIVE: * To examine the efficacy of adding amikacin to fluoroquinolone-based antimicrobial prophylaxis in preventing transrectal ultrasonography-guided prostate biopsy (TGB) associated infections. PATIENTS AND METHODS: * Infections after TGB were compared before adding amikacin to antimicrobial prophylaxis (2006) with those that occurred after adding amikacin to the prophylaxis (2007 and 2008). * During both periods antimicrobial prophylaxis consisted of ciprofloxacin, co-amoxiclav and metronidazole except after August 2008 when co amoxiclav was discontinued. * Amikacin was added to the prophylaxis protocol in the period 2007 and 2008. RESULTS: * Before adding amikacin 11 of 281 (3.9%) patients developed infections after TGB (seven urinary tract infections (UTIs) and seven bacteraemias) whereas after adding amikacin six UTIs and two bacteraemias occurred in 590 (1.4%) patients. * In both periods, most of the strains causing the infections were ciprofloxacin resistant (2006: 13 of 14; 2007 and 2008: seven of eight). * Overall, there is strong statistical evidence that the total infection rate was significantly reduced after the inclusion of amikacin into the prostate biopsy prophylaxis regimen. * In 2007 and 2008 when amikacin was included in prophylaxis, the bacteraemia rate was reduced to just over one-tenth of the rate in 2006 before introducing amikacin (P= 0.002). * Although just failing to reach the conventional significance level of 0.05, the evidence suggests a reduction in UTI by an estimated 60% after adding amikacin. CONCLUSION: * We conclude that adding amikacin to fluoroquinolone-based antimicrobial prophylaxis in areas with high fluoroquinolone resistance confers significant benefit in preventing infections after TGB. PMID- 21029319 TI - Microarray-based comparison of genetic differences between strains of Streptomyces turgidiscabies with focus on the pathogenicity island. AB - The areas of the pathogenicity island (PAI) designated as 'colonization region' (CR) and 'toxicogenic region' (TR) [Lerat et al. (2009) Mol. Plant Pathol. 10, 579-585] contain genes required for virulence and phytoxin production, respectively, in Streptomyces spp. causing common scab on potatoes. The PAI was tested for genetic variability by microarray analysis in strains of S. turgidiscabies isolated from potatoes in Finland. The data revealed four types of PAI based on divergent CR and TR which occurred in different combinations. Only one PAI type was highly similar to S. scabies (strains 87.22 and ATTC49173). Using probes designed for the predicted genes of S. scabies, two gene clusters in S. scabies appeared to be similar to most strains of S. turgidiscabies and contained PAI genes corresponding to CR and TR. They were located approximately 5 Mb apart in the S. scabies genome, as compared with only 0.3 Mb in S. turgidiscabies Car8. Data from comparative genomic hybridization with probes designed for S. scabies genes and for the PAI of S. turgidiscabies were compared by multilocus cluster analysis, which revealed two strains of S. turgidiscabies that were very closely related at the whole-genome level, but contained distinctly different PAIs. The type strain of S. reticuliscabiei (DSM41804; synonymous to S. turgidiscabies) was clustered with S. turgidiscabies. Taken together, the data indicate wide genetic variability of PAIs among strains of S. turgidiscabies, and demonstrate that PAI is made up of a mosaic of regions which may undergo independent evolution. PMID- 21029320 TI - Lipopolysaccharide mobility in leaf tissue of Arabidopsis thaliana. AB - Bacterial lipopolysaccharides (LPS) are triggers of defence responses in plants, and induce local as well as systemic acquired resistance. Arabidopsis thaliana plants pretreated with LPS show an increased resistance to the virulent bacterial plant pathogen Pseudomonas syringae pv. tomato DC3000. To investigate the mobilization and transport of LPS in Arabidopsis leaves, fluorescently labelled LPS (Alexa Fluor(r) 488 conjugate) from Salmonella minnesota was used. Leaves were pressure infiltrated with fluorescein-labelled LPS and fluorescence microscopy was used to follow the movement and localization of LPS as a function of time. The observation of leaves 1 h after supplementation with fluorescein labelled LPS revealed a fluorescent signal in the intercellular space. Capillary zone electrophoresis was used for the detection and analysis of the labelled LPS in directly treated leaves and systemic leaves. In addition, gel electrophoresis was used to confirm LPS mobilization. The results indicated that LPS mobilization/translocation occurs through the xylem from local, treated leaves to systemic, untreated leaves. Consequently, care should be taken when ascribing the observed biochemical responses and induced resistance from LPS perception as being uniquely local or systemic, as these responses might overlap because of the mobility of LPS in the plant vascular system. PMID- 21029321 TI - Homodimerization of pokeweed antiviral protein as a mechanism to limit depurination of pokeweed ribosomes. AB - Ribosome inactivating proteins are glycosidases synthesized by many plants and have been hypothesized to serve in defence against pathogens. These enzymes catalytically remove a conserved purine from the sarcin/ricin loop of the large ribosomal RNA, which has been shown in vitro to limit protein synthesis. The resulting toxicity suggests that plants may possess a mechanism to protect their ribosomes from depurination during the synthesis of these enzymes. For example, pokeweed antiviral protein (PAP) is cotranslationally inserted into the lumen of the endoplasmic reticulum and travels via the endomembrane system to be stored in the cell wall. However, some PAP may retrotranslocate across the endoplasmic reticulum membrane to be released back into the cytosol, thereby exposing ribosomes to depurination. In this work, we isolated and characterized a complexed form of the enzyme that exhibits substantially reduced activity. We showed that this complex is a homodimer of PAP and that dimerization involves a peptide that contains a conserved aromatic amino acid, tyrosine 123, located in the active site of the enzyme. Bimolecular fluorescence complementation demonstrated that the homodimer may form in vivo and that dimerization is prevented by the substitution of tyrosine 123 for alanine. The homodimer is a minor form of PAP, observed only in the cytosol of cells and not in the apoplast. Taken together, these data support a novel mechanism for the limitation of depurination of autologous ribosomes by molecules of the protein that escape transport to the cell wall by the endomembrane system. PMID- 21029322 TI - Mass spectrometry-based metabolomics application to identify quantitative resistance-related metabolites in barley against Fusarium head blight. AB - Quantitative resistance is generally controlled by several genes. More than 100 resistance quantitative trait loci (QTLs) have been identified in wheat and barley against Fusarium head blight (FHB), caused by Gibberella zeae (anamorph: Fusarium graminearum), implying the possible occurrence of several resistance mechanisms. The objective of this study was to apply metabolomics to identify the metabolites in barley that are related to resistance against FHB. Barley genotypes, Chevron and Stander, were inoculated with mock or pathogen during the anthesis stage. The disease severity was assessed as the proportion of spikelets diseased. The genotype Chevron (0.33) was found to have a higher level of quantitative resistance than Stander (0.88). Spikelet samples were harvested at 48 h post-inoculation; metabolites were extracted and analysed using an LC-ESI LTQ-Orbitrap (Thermo Fisher, Waltham, MA, USA). The output was imported to an XCMS 1.12.1 platform, the peaks were deconvoluted and the adducts were sieved. Of the 1826 peaks retained, a t-test identified 496 metabolites with significant treatment effects. Among these, 194 were resistance-related (RR) constitutive metabolites, whose abundance was higher in resistant mock-inoculated than in susceptible mock-inoculated genotypes. Fifty metabolites were assigned putative names on the basis of accurate mass, fragmentation pattern and number of carbons in the formula. The RR metabolites mainly belonged to phenylpropanoid, flavonoid, fatty acid and terpenoid metabolic pathways. Selected RR metabolites were assayed in vitro for antifungal activity on the basis of fungal biomass production. The application of these RR metabolites as potential biomarkers for screening and the potential of mass spectrometry-based metabolomics for the identification of gene functions are discussed. PMID- 21029323 TI - Effector-triggered innate immunity contributes Arabidopsis resistance to Xanthomonas campestris. AB - Xanthomonas campestris pv. campestris, the causal agent of black rot disease, depends on its type III secretion system (TTSS) to infect cruciferous plants, including Brassica oleracea, B. napus and Arabidopsis. Previous studies on the Arabidopsis-Pseudomonas syringae model pathosystem have indicated that a major function of TTSS from virulent bacteria is to suppress host defences triggered by pathogen-associated molecular patterns. Similar analyses have not been made for the Arabidopsis-X. campestris pv. campestris pathosystem. In this study, we report that X. campestris pv. campestris strain 8004, which is modestly pathogenic on Arabidopsis, induces strong defence responses in Arabidopsis in a TTSS-dependent manner. Furthermore, the induction of defence responses and disease resistance to X. campestris pv. campestris strain 8004 requires NDR1 (NON RACE-SPECIFIC DISEASE RESISTANCE1), RAR1 (required for Mla12 resistance) and SGT1b (suppressor of G2 allele of skp1), suggesting that effector-triggered immunity plays a large role in resistance to this strain. Consistent with this notion, AvrXccC, an X. campestris pv. campestris TTSS effector protein, induces PR1 expression and confers resistance in Arabidopsis in a RAR1- and SGT1b dependent manner. In rar1 and sgt1b mutants, AvrXccC acts as a virulence factor, presumably because of impaired resistance gene function. PMID- 21029324 TI - Evaluation of reference genes for quantitative reverse-transcription polymerase chain reaction normalization in infected tomato plants. AB - The quantification of messenger RNA expression levels by real-time reverse transcription polymerase chain reaction requires the availability of reference genes that are stably expressed regardless of the experimental conditions under study. We examined the expression variations of a set of eight candidate reference genes in tomato leaf and root tissues subjected to the infection of five taxonomically and molecularly different plant viruses and a viroid, inducing diverse pathogenic effects on inoculated plants. Parallel analyses by three commonly used dedicated algorithms, geNorm, NormFinder and BestKeeper, showed that different viral infections and tissues of origin influenced, to some extent, the expression levels of these genes. However, all algorithms showed high levels of stability for glyceraldehyde 3-phosphate dehydrogenase and ubiquitin, indicated as the most suitable endogenous transcripts for normalization in both tissue types. Actin and uridylate kinase were also stably expressed throughout the infected tissues, whereas cyclophilin showed tissue-specific expression stability only in root samples. By contrast, two widely employed reference genes, 18S ribosomal RNA and elongation factor 1alpha, demonstrated highly variable expression levels that should discourage their use for normalization. In addition, expression level analysis of ascorbate peroxidase and superoxide dismutase showed the modulation of the two genes in virus-infected tomato leaves and roots. The relative quantification of the two genes varied according to the reference genes selected, thus highlighting the importance of the choice of the correct normalization method in such experiments. PMID- 21029325 TI - Natural variation in priming of basal resistance: from evolutionary origin to agricultural exploitation. AB - Biotic stress has a major impact on the process of natural selection in plants. As plants have evolved under variable environmental conditions, they have acquired a diverse spectrum of defensive strategies against pathogens and herbivores. Genetic variation in the expression of plant defence offers valuable insights into the evolution of these strategies. The 'zigzag' model, which describes an ongoing arms race between inducible plant defences and their suppression by pathogens, is now a commonly accepted model of plant defence evolution. This review explores additional strategies by which plants have evolved to cope with biotic stress under different selective circumstances. Apart from interactions with plant-beneficial micro-organisms that can antagonize pathogens directly, plants have the ability to prime their immune system in response to selected environmental signals. This defence priming offers disease protection that is effective against a broad spectrum of virulent pathogens, as long as the augmented defence reaction is expressed before the invading pathogen has the opportunity to suppress host defences. Furthermore, priming has been shown to be a cost-efficient defence strategy under relatively hostile environmental conditions. Accordingly, it is possible that selected plant varieties have evolved a constitutively primed immune system to adapt to levels of disease pressure. Here, we examine this hypothesis further by evaluating the evidence for natural variation in the responsiveness of basal defence mechanisms, and discuss how this genetic variation can be exploited in breeding programmes to provide sustainable crop protection against pests and diseases. PMID- 21029326 TI - Genome-wide analysis of phenylpropanoid defence pathways. AB - Phenylpropanoids can function as preformed and inducible antimicrobial compounds, as well as signal molecules, in plant-microbe interactions. Since we last reviewed the field 8 years ago, there has been a huge increase in our understanding of the genes of phenylpropanoid biosynthesis and their regulation, brought about largely by advances in genome technology, from whole-genome sequencing to massively parallel gene expression profiling. Here, we present an overview of the biosynthesis and roles of phenylpropanoids in plant defence, together with an analysis of confirmed and predicted phenylpropanoid pathway genes in the sequenced genomes of 11 plant species. Examples are provided of phylogenetic and expression clustering analyses, and the large body of underlying genomic data is provided through a website accessible from the article. PMID- 21029327 TI - Higher proportion of fast-twitch (type II) muscle fibres in idiopathic inflammatory myopathies - evident in chronic but not in untreated newly diagnosed patients. AB - OBJECTIVE: Polymyositis and dermatomyositis are idiopathic, inflammatory myopathies characterized by proximal muscle fatigue. Conventional immunosuppressive treatment gives a variable response. Biopsies from chronic patients display a low proportion type I and a high proportion of type II muscle fibres. This raised a suspicion that the low proportion of type I fibres might play a role in the muscle fatigue. AIM: To investigate whether the muscle fibre attributes evident in chronic myositis are characteristic for the polymyositis and dermatomyosistis diseases themselves. METHODS: Muscle biopsies were obtained from thigh muscle from untreated patients (n = 18), treated responders (n = 14) and non-responders (n = 6) and from healthy controls (n = 11), respectively. For clinical evaluations, creatine kinase, functional index of myositis and cumulative dose of cortisone were established. RESULTS: Chronic patients had a lower proportion of type I fibres and a higher proportion of type II fibres compared to untreated myositis patients and healthy controls. Fibre cross sectional area (CSA) did not differ between patients and healthy individuals but all women had a 20% smaller type II fibre CSA compared to men. CONCLUSIONS: Untreated polymyositis and dermatomyositis patients and healthy controls have a different fibre type composition than chronic polymyositis and dermatomyositis patients. Fibre CSA did not differ between healthy controls or any of the patient groups. A low proportion of oxidative muscle fibres can therefore be excluded as a contributing factor causing muscle fatigue at disease onset and the gender difference should be taken into consideration when evaluating fibre CSA in myositis. PMID- 21029328 TI - The alpha-MSH analogue AP214 attenuates rise in pulmonary pressure and fall in ejection fraction in lipopolysaccharide-induced systemic inflammatory response syndrome in pigs. AB - BACKGROUND: The effect of an alpha-melanocyte stimulating hormone (alpha-MSH) analogue (AP214) on experimentally endotoxin-induced systemic inflammatory response syndrome (SIRS) was studied, because alpha-MSH in rodent models has shown promise in attenuating inflammatory response markers and associated organ damage in SIRS. SIRS is associated with considerable morbidity and mortality. Consequently, new treatment modalities are still warranted to address the different aspects of the pathophysiological process. METHODS: SIRS was induced by lipopolysaccharide (LPS) (Escherichia coli endotoxin) infusion in anaesthetized Danish Landrace pigs (20-25 kg). The pigs received an alpha-MSH analogue (AP214) or saline as a bolus at the initiation of the LPS infusion. The hemodynamic response was registered as well as echocardiographic indices of left ventricular function. RESULTS: The cardiovascular response was recorded together with echocardiographic indices of left ventricular function in control and in intervention animals. AP214 reduced the early peak in pulmonary pressure and pulmonary vascular resistance by approximately 33%. Furthermore, AP214 prevented the decline in left ventricular fractional shortening as observed in the control group. Mean change and standard deviation in fractional shortening (DeltaFS) in control group: - 7.3 (4.7), AP214 (low dose): 0.9 (8.2) and AP214 (high dose) 4.1 (6.0), P < 0.05 for both intervention groups versus control. CONCLUSIONS: In the porcine model, the peak increase in pulmonary pressure was attenuated, and the LPS-induced decline in left ventricular function was prevented. PMID- 21029329 TI - Cerebral and muscle oxygenation changes during static and dynamic knee extensions to voluntary fatigue in healthy men and women: a near infrared spectroscopy study. AB - The aim of the study was to examine the changes in cerebral and muscle blood volume (Cbv, Mbv) and oxygenation (Cox, Mox) during static and dynamic knee extensions to fatigue in men (N=10; 29+/-9 years) and women (N=14; 27+/-8 years). After assessment of 1 repetition maximum (1RM) during unilateral knee extensions with the dominant limb, each subject exercised at 50%, 75% and 100% of 1 RM in random order on separate occasions. Simultaneous changes in Cbv, Cox, Mbv and Mox from the contralateral prefrontal lobe and the dominant limb were measured by near infrared spectroscopy. During all three contractions, Cbv and Cox increased while Mbv and Mox decreased until fatigue in both genders. There were no signs of levelling off or decline in Cbv and Cox during any of these contractions, implying that there was no reduction in cerebral neuronal activation. Conversely, there was a rapid decline in Mbv and Mox during the early stages of the contractions, with a plateau or slight increase towards the end. The respective delta values at 50%, 75% and 100% of 1RM for Cbv (0.088 versus 0.062 versus 0.070), Cox (0.042 versus 0.033 versus 0.038), Mbv (-0.225 versus -0.198 versus 0.196), and Mox (-0.169 versus -0.146 versus -0.158) were not significantly different in the total group (N=24). These findings suggest that fatigue during resistance exercise lasting up to 60 s is mediated peripherally because of reduced blood volume and oxygen availability and is independent of the type and intensity of muscle contraction and gender. PMID- 21029330 TI - Unusual cause of biliary colic in a Swiss farmer. PMID- 21029331 TI - Enduring amalgam: no requiem needed. PMID- 21029332 TI - Dentin/Enamel bonding. PMID- 21029333 TI - A multidisciplinary approach to the functional and esthetic rehabilitation of amelogenesis imperfecta and open bite deformity: a case report. AB - The treatment of amelogenesis imperfecta (AI) with an anterior open bite (AOB) is a challenge for the clinician and often requires a multidisciplinary team of specialists. Most often, patients suffering from these conditions are young and a good functional and esthetic long-term result must be aspired. This clinical report illustrates the orthodontic, maxillofacial, restorative, and prosthodontic rehabilitation of a 20-year-old woman with a hypoplastic form of AI and an AOB malocclusion, having received treatment for the last 6 years. It included adhesive resin composite restorations, orthodontical and maxillofacial surgery with a one-piece Le Fort I osteotomy, and a genioplasty. Subsequent prosthodontic therapy consisted of 28 all-ceramic crowns whereby a solid interdigitation, a canine guidance, and consistent and regular contacts between tooth crowns could be achieved to assure a good functional and esthetic oral situation. The tooth preparation techniques guaranteed minimally invasive treatment. The patient was affected very positively. CLINICAL SIGNIFICANCE: This article describes an interdisciplinary approach to the successful treatment of a patient with a hypoplastic form of amelogenesis imperfecta over a period of 6 years. It starts with a discussion of the conservative steps taken during adolescence and concludes with the final prosthetic rehabilitation with all-ceramic crowns after reaching adulthood. PMID- 21029334 TI - Orthodontic treatment of a congenitally missing maxillary lateral incisor. AB - Clinicians agree that, regardless of gender or race, tooth agenesis has become more prominent in recent societies. The congenital absence of one or more maxillary lateral incisors poses a challenge to effective treatment planning for the restorative dentist. However, the one-sided orthodontic approach of just moving canines mesially to eliminate restorative procedures leads to compromise. Adult patients presenting with malocclusions, missing lateral incisors, or anterior crowding but who fail to get proper orthodontic treatment, requesting instead esthetic solutions that do not establish a stable occlusion, proper alignment, and proper axial inclination of the teeth will have compromised esthetic and periodontal results. An evaluation of anterior smile esthetics must include both static and dynamic evaluations of frontal and profile views to optimize both dental and facial appearance. This article presents how orthodontics is combined with other specialties in treating a congenitally missing lateral incisor. One case is used to illustrate how orthodontic treatment is progressed in collaboration with other specialists. CLINICAL SIGNIFICANCE: Patients with missing teeth, crowding, midline deviation, unesthetic gingival contours, or other restorative needs may require the interaction between various specialists. For the successful treatment of orthodontic-restorative patients, an interdisciplinary team effort is vital. PMID- 21029335 TI - In vivo temperature measurement: tooth preparation and restoration with preheated resin composite. AB - STATEMENT OF THE PROBLEM: Composite preheating has shown to improve material physical properties in vitro, but no data exist on the use of this technique in vivo during placement. PURPOSE: The study aims to measure in vivo prepared tooth surface temperature during a restorative procedure using resin composite either at room temperature (23.6 degrees C) or preheated to 54.7 degrees C in a commercial compule heating device set to heat at 60 degrees C. METHODS: Class I preparations (N=3) were made on a patient requiring multiple posterior restorations. A probe containing two thermocouples was used to record temperature values at the tooth pulpal floor and 2mm higher (top of the tooth preparation/restoration) after tooth preparation (prep), acid etching (etch), placement and curing of a bonding agent (BA), and during placement of composite used at room temperature (RT) or preheated in a commercial device (Calset(TM) , AdDent Inc., Danbury, CT, USA) set to 60 degrees C. Data were compared with two way analysis of variance, Tukey-Kramer post hoc test (alpha=0.05). RESULTS: No significant difference in pulpal floor temperature existed between prep (27.8 degrees +/-1.3 degrees C) and etch (26.3 degrees +/-1.3 degrees C), which were significantly lower than BA (30.5 degrees +/-1.3 degrees C) (p=0.0001). Immediate placement of preheated composite resulted in significantly higher pulpal floor (36.2 degrees +/-1.9 degrees C) (p=0.0025) and top composite temperatures (38.4 degrees +/-2.2 degrees C) (p=0.0034) than RT values (30.4 degrees +/-2.2 degrees C and 29.6 degrees +/-0.9 degrees C, respectively). CONCLUSIONS: In vivo use and placement of preheated resin composite resulted in temperature increase of 6 degrees to 8 degrees C than room temperature material. These values, however, were much lower than expected. CLINICAL SIGNIFICANCE: Although having many potential benefits, composite preheating may not be as clinically effective in delivering resin of predetermined temperature at the time of cure as laboratory experiments would suggest. Despite only moderate composite temperature increase over use of room temperature material, preheating still provides advantages in terms of ease of handling and placement. PMID- 21029336 TI - Effect of artificial aging on the roughness and microhardness of sealed composites. AB - STATEMENT OF THE PROBLEM: The application of surface sealant could improve the surface quality and success of composite restorations; however, it is important to assess the behavior of this material when subjected to aging procedures. PURPOSE: To evaluate the effect of artificial aging on the surface roughness and microhardness of sealed microhybrids and nanofilled composites. MATERIALS AND METHODS: One hundred disc-shaped specimens were made for each composite. After 24 hours, all samples were polished and surface sealant was applied to 50 specimens of each composite. Surface roughness (Ra) was determined with a profilometer and Knoop microhardness was assessed with a 50-g load for 15 seconds. Ten specimens of each group were aged during 252 hours in a UV accelerated aging chamber or immersed for 28 days in cola soft drink, orange juice, red wine staining solutions, or distilled water. Data were analyzed by two way analysis of variance and Fischer's test (alpha=0.05). RESULTS: Artificial aging decreased microhardness values for all materials, with the exceptions of Vit-l-escence (Ultradent Products Inc., South Jordan UT, USA) and Supreme XT (3M ESPE, St. Paul, MN, USA) sealed composites; surface roughness values were not altered. Water storage had less effect on microhardness, compared with the other aging processes. The sealed materials presented lower roughness and microhardness values, when compared with unsealed composites. CONCLUSIONS: Aging methods decreased the microhardness values of a number of composites, with the exception of some sealed composites, but did not alter the surface roughness of the materials. CLINICAL SIGNIFICANCE: The long-term maintenance of the surface quality of materials is fundamental to improving the longevity of esthetic restorations. In this manner, the use of surface sealants could be an important step in the restorative procedure using resin-based materials. PMID- 21029337 TI - Multifunctional uses of a novel ceramic-lithium disilicate. PMID- 21029338 TI - ASH position paper: Adherence and persistence with taking medication to control high blood pressure. AB - Nonadherence and poor or no persistence in taking antihypertensive medications results in uncontrolled high blood pressure, poor clinical outcomes, and preventable health care costs. Factors associated with nonadherence are multilevel and relate not only to the patient, but also to the provider, health care system, health care organization, and community. National guideline committees have called for more aggressive approaches to implement strategies known to improve adherence and technologies known to enable changes at the systems level, including improved communication among providers and patients. Improvements in adherence and persistence are likely to be achieved by supporting patient self-management, a team approach to patient care, technology-supported office practice systems, better methods to measure adherence, and less clinical inertia. Integrating high blood pressure control into health care policies that emphasize and improve prevention and management of chronic illness remains a challenge. Four strategies are proposed: focusing on clinical outcomes; empowering informed, activated patients; developing prepared proactive practice teams; and advocating for health care policy reform. With hypertension remaining the most common reason for office visits, the time is now. PMID- 21029339 TI - Safety and tolerability of the direct renin inhibitor aliskiren: a pooled analysis of clinical experience in more than 12,000 patients with hypertension. AB - While the safety of renin-angiotensin system (RAS)-blocking drugs such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers is well known, less is known about the new direct renin inhibitor aliskiren. The authors pooled data from 12 randomized controlled trials of aliskiren in patients with hypertension and analyzed the incidence and types of adverse events (AEs) and laboratory abnormalities. Studies were characterized as short-term (<=2 months) placebo-controlled or long-term (>2 months) active-controlled. Relative risks for AEs of particular interest for RAS blockers were calculated. In short term studies, AEs occurred in similar proportions of aliskiren 150 mg and 300 mg (33.6% and 31.6%, respectively) and placebo treatment groups (36.8%). In long term studies, a lower proportion of patients treated with aliskiren 150 mg and 300 mg had AEs (33.7% and 43.2%, respectively) than those treated with ACE inhibitors (60.1%), angiotensin receptor blockers (53.9%), and thiazide diuretics (48.9%). Events of special interest, including angioedema, hyperkalemia, and diarrhea occurred in similar proportions of patients taking aliskiren, placebo, and comparator agents. In studies of up to 36 weeks, patients treated with aliskiren were significantly less likely to develop cough than those treated with ACE inhibitors. At the registered doses of 150 mg and 300 mg daily, aliskiren has safety and tolerability profiles similar to placebo, other RAS blockers, and diuretics. Cough rates are lower with aliskiren compared with ACE inhibitors. PMID- 21029340 TI - Morning hypertension assessed by home monitoring is a strong predictor of concentric left ventricular hypertrophy in patients with untreated hypertension. AB - This study was performed to test whether morning hypertension defined by the morning-evening difference in home blood pressure (BP) (MEdif) and the average of morning and evening BP (MEave) is a determinant of concentric left ventricular hypertrophy (LVH). The authors enrolled patients with untreated hypertension and performed echocardiography and home BP monitoring for 14 consecutive days. All patients were classified into 4 groups by the MEave and MEdif and morning hypertension was defined by MEave >=135 mm Hg and MEdif >=15 mm Hg. Left ventricular (LV) geometry was classified as normal, concentric remodeling, eccentric LVH, or concentric LVH. The morning hypertensive patients had a higher LV mass index and relative wall thickness than the other groups. According to multivariable logistic regression analysis, morning hypertensive patients had a significantly increased risk of the concentric LVH (odds ratio, 6.5; 95% confidence interval, 2.5-17.2; P<.001) compared with home normotensive patients with MEdif <15 mm Hg, after adjusting for confounders. Moreover, even among the home normotensives (white-coat hypertensives), patients with MEdif >=15 mm Hg had a higher percentage of concentric remodeling than those with MEdif <15 mm Hg (32.5% vs 14.7%, P=.017). Morning hypertension defined by the MEdif and MEave is a strong determinant of concentric LVH, suggesting that this definition could be used to determine the cardiovascular risk of morning hypertension. PMID- 21029341 TI - Prevalence of self-reported hypertension, advice received from health care professionals, and actions taken to reduce blood pressure among US adults- HealthStyles, 2008. AB - Lifestyle changes, such as changes in diet and exercise, are recommended to lower blood pressure (BP) in adults. Using data from the 2008 HealthStyles survey, the authors estimated the prevalence of self-reported hypertension, advice received from health professionals, and actions taken to reduce BP. Among 5399 respondents, 25.8% had hypertension and 79.8% of these were currently taking antihypertensive medications. Overall, 21.0% to 24.4% reported receiving advice to adopt specific behavior changes, with younger adults and women having a lower prevalence of receiving advice. Blacks had the highest prevalence among the racial/ethnic groups of receiving advice, and household income was associated with receiving advice. More than half of respondents took action following the receipt of advice. Women were more likely than men to follow advice to go on a diet. Although many patients were following advice from their health professional and making lifestyle changes to decrease BP, the proportion of patients making changes remains suboptimal. Receiving advice from health professionals and following recommendations to reduce or control high BP are essential to hypertension management. Counseling on lifestyle modification should continue to be an integral component of visits to health professionals. PMID- 21029342 TI - Actions taken to reduce sodium intake among adults with self-reported hypertension: HealthStyles survey, 2005 and 2008. AB - Consuming high amounts of dietary sodium is associated with hypertension. The authors analyzed the HealthStyles 2005 and 2008 survey for behaviors to lower blood pressure related to dietary sodium, including the reduction of sodium intake and reading food labels for sodium content among hypertensives. All estimates were based on self-reported data. The relative percent change (RPC) in the prevalence of these behaviors between 2005 and 2008 was assessed. During the 3-year period, there were increases in the prevalence of reducing dietary sodium (RPC=17.2%, 56.6% in 2008 vs 48.3% in 2005; P<.05) and reading food labels for sodium content (RPC=7.9%, 53.0% vs 49.1%; P<.05). In 2005, the proportion of hypertensive adults who reported reducing dietary sodium was higher for persons 65 years and older, for blacks, for those with income <$25,000, and for those with more than a high school education compared with those in their comparison groups. In 2008, those aged 65 years and older had the highest percentage, while Hispanics and blacks had essentially the same percentage for reducing sodium. Based on 2005 and 2008 HealthStyles surveys, about half of hypertensive patients reported reducing their intake of sodium and reading food labels for salt. Health care providers should emphasize the importance of knowing the daily recommended limit for dietary sodium to help adults lower this intake. PMID- 21029343 TI - A hypertension risk score for middle-aged and older adults. AB - Determining which demographic and medical variables predict the development of hypertension could help clinicians stratify risk in both prehypertensive and nonhypertensive persons. Subject-level data from 2 community-based biracial cohorts were combined to ascertain the relationship between baseline characteristics and incident hypertension. Hypertension, defined as diastolic blood pressure >=90 mm Hg, systolic blood pressure >=140 mm Hg, or reported use of medication known to treat hypertension, was assessed prospectively at 3, 6, and 9 years. Internal validation was performed by the split-sample method with a 2:1 ratio for training and testing samples, respectively. A scoring algorithm was developed by converting the multivariable regression coefficients to integer values. Age, level of systolic or diastolic blood pressure, smoking, family history of hypertension, diabetes mellitus, high body mass index, female sex, and lack of exercise were associated with the development of hypertension in the training sample. Regression models showed moderate to high capabilities of discrimination between hypertension vs nonhypertension (area under the receiver operating characteristic curve 0.75-0.78) in the testing sample at 3, 6, and 9 years of follow-up. This risk calculator may aide health care providers in guiding discussions with patients about the risk for progression to hypertension. PMID- 21029344 TI - Combination angiotensin receptor blocker-neutral endopeptidase inhibitor provides additive blood pressure reduction over angiotensin receptor blocker alone. PMID- 21029345 TI - Framingham hypertension risk score: the prevalence estimation of hypertension after 1 year in the population. PMID- 21029346 TI - Safety of spectator sports: blood pressure and heart rate responses in baseball and football fans. PMID- 21029347 TI - Low-dose statin therapy improves endothelial function in type 2 diabetic patients with normal serum total cholesterol: a randomized placebo-controlled study. AB - The authors sought to explore the effect of low-dose atorvastatin on endothelial function in normocholesterolemic patients with type 2 diabetes mellitus without evidence of coronary disease. Sixty patients with type 2 diabetes mellitus, normal serum cholesterol, and normal exercise test results were enrolled. Initial assessment was performed by measurement of the brachial artery diameter and flow velocity both at baseline and after induced hyperemia. Patients were randomly assigned to receive either atorvastatin 10 mg daily for 4 weeks (atorvastatin group=30 patients) or matched placebo for the same period (placebo group=30 patients). Follow-up assessment of the brachial artery diameter and flow velocity (both baseline and hyperemic) was performed after 4 weeks. Initially, no significant difference was found between the two groups regarding brachial artery diameter or flow velocity, both at baseline and at peak hyperemia (P>.05 for all). At follow-up, there was a significantly higher flow velocity at baseline (P<.05) and a significantly higher percent increase of brachial artery diameter (from baseline to peak hyperemia) in the atorvastatin group (P<.05). In patients with type 2 diabetes mellitus and normal serum cholesterol without evidence of coronary disease, low-dose atorvastatin improves endothelial function. PMID- 21029348 TI - US trends in glycemic control, treatment, and comorbidity burden in patients with diabetes. AB - This study explored trends over time in diabetes prevalence, glycemic control, and antidiabetic therapy choices among adults (18-64 years) and older adults (>= 65 years). Factors that predict diabetes outcomes were explored. The study was cross-sectional, with data from the 1999 to 2004 National Health and Nutrition Examination Survey. The study group consisted of 1211 persons with self-reported diabetes. Other information obtained from the study included self-reported medication for diabetes, hypertension, stroke, heart failure, and health status. The survey also provided examination or laboratory tests of obesity, nephropathy, and glycosylated hemoglobin level. Descriptive and logistic regression analyses were used in the study. The study showed that the proportion of diabetics with good glycemic control increased during the period from 1999 to 2004. However, nearly half of the adults and one third of older adults with diabetes did not reach glycemic control in 2003-2004. Overall, 59% of adults and 46% of older adults were obese. There was a high prevalence of hypertension, heart failure, stroke, and nephropathy among patients with diabetes, especially in older adults. The results indicate a high percentage of poor glycemic control among persons with diabetes. There were also a substantial number of comorbid conditions associated with diabetes. PMID- 21029349 TI - Facet pain in thoracic compression fractures. AB - OBJECTIVE: To determine if thoracic facet joints may be a significant secondary pain generator in patients with compression fractures. Traditionally, pain from vertebral compression fractures has been attributed to vertebral body itself. Compression fractures have been shown to increase thoracic kyphosis and thereby increase the thoracic flexion moment; these changes eventually increase the shear stress on the posterior elements. DESIGN: We present a small case series of patients with thoracic compression fractures managed with intra-articular facet injections. SETTING: Tertiary care academic medical center. PARTICIPANTS: Two patients with thoracic compression fractures. INTERVENTIONS: The subjects received fluoroscopically guided thoracic facet steroid injections for pain management. MAIN OUTCOME: Change in verbal analog pain score. RESULTS: Patients with thoracic compression fractures received significant long-lasting relief after receiving fluoroscopically guided intra-articular injections. CONCLUSION: Facet joints may be abnormally stressed due to the increasing thoracic flexion moment in anterior compression fractures, which may serve as a secondary pain generator; intra-articular facet blocks may be an alternative to vertebroplasty. PMID- 21029351 TI - Predictors of pain 12 months after serious injury. AB - OBJECTIVE: The majority of patients will report pain 12 months after a serious injury. Determining the independent risk factors for pain after serious injury will establish the degree to which high-risk patients can be detected in the acute setting and the viability of early triage to specialist pain services. DESIGN: A prospective cohort study of patients following serious injury was conducted. The initial assessment comprised a comprehensive battery of known and possible risk factors for persistent pain. Patients were assessed at 12 months for pain severity and for the presence of chronic pain. RESULTS: Two hundred ninety patients underwent an initial assessment of whom 238 (82%) were followed up at 12 months. At 12 months, 171 (72%) patients reported some pain over the past 24 hours. Thirty-five patients (14.7%) reported chronic pain. Five factors independently predicted the 24-hour pain severity: preinjury physical role function, preinjury employment status, initial 24 hours pain score, higher beliefs in the need for medication, and compensable injury (R(2) = 0.21, P < 0.0001). Four factors predicted the presence of chronic pain at 12 months: not working prior to injury, total Abbreviated Injury Scale, initial pain severity, and initial pain control attitudes (pseudo R(2) = 0.24, P = 0.0001). CONCLUSIONS: Factors present at the time of injury can allocate patients into high- or low risk groups. The majority of cases of chronic pain emerging from the high-risk group warrant more intense clinical attention. We recommend recording these factors in discharge documentation as indicators of persistent pain. PMID- 21029350 TI - Ischemic hypersensitivity in irritable bowel syndrome patients. AB - OBJECTIVE: Mixed evidence exists regarding whether irritable bowel syndrome (IBS) patients show increased somatic pain perception compared with controls. The current study used a deep, tonic somatic pain stimulus (ischemic pain) to evaluate somatic hypersensitivity in IBS patients. METHODS: A total of 27 diarrhea-predominant and 15 constipation-predominant IBS patients, and 29 controls participated in the study. The modified submaximal effort tourniquet procedure was performed to induce ischemic arm pain, and the time required to reach pain threshold and pain tolerance were recorded in seconds. All subjects completed the Functional Bowel Disease Severity Index (FBDSI) scale as well as several psychosocial instruments. Group differences for threshold and tolerance were determined using a series of one-way anova tests followed by Tukey comparisons. RESULTS: IBS patients had a shorter time to ischemic threshold (F = 34.606, P < 0.001) and tolerance (F = 38.656, P < 0.001) compared with controls; however, the groups did not differ on ratings of pain at the time of tolerance. IBS patients had a higher rating on the FBDSI scale compared with controls (P < 0.001), and ischemic pain threshold was negatively correlated with the FBDSI score. CONCLUSIONS: The results of this study suggest that a widespread alteration in central pain processing in IBS patients may be present as they display hypersensitivity to ischemic arm pain, and ischemic pain threshold was associated with clinical symptoms. These findings could reflect a dysfunction in inhibitory pain systems in IBS patients, as ischemic (deep) pain may be under tonic inhibitory control. PMID- 21029352 TI - Stability and tolerability of high concentrations of intrathecal bupivacaine and opioid mixtures in chronic noncancer pain: an open-label pilot study. AB - OBJECTIVE: To evaluate the stability and tolerability of high concentrations of bupivacaine-opioid solutions when used by intrathecal infusion. DESIGN: Prospective, open label, pilot cohort study. SETTING: Outpatients at a University medical center. PATIENTS: Twelve patients with inadequate pain control already receiving intrathecal opioids and low dose bupivacaine. INTERVENTIONS: Increasing concentrations and doses of bupivacaine between 1 and 5% were prescribed to be added to a stable daily opioid dose. Drug infusate sampling and analysis using high performance liquid chromatography. OUTCOME MEASURES: Physical examination, assessment of pain and function between (0-60 days) using a linear visual analog scale, and the Oswestry Disability Index. RESULTS: Final daily doses of bupivacaine were 4-21.4 mg delivered at measured concentrations of 0.4-3.7%. Two patients experienced reversible motor weakness at 6 mg of bupivacaine/day. The in vitro and in vivo sampling of concentrations up to 3.7% of bupivacaine demonstrated that the stability for bupivacaine with morphine (1.2-3%) or hydromorphone (0.4-1%) was >96% of the manufactured concentration. There were no clinically significant changes in the visual analog pain scale or the Oswestry Disability Index. CONCLUSIONS: This in vivo study demonstrates excellent stability of high concentrations of intrathecal bupivacaine and opioid mixtures. No nonreversible neurological complications were identified in patients receiving daily doses of bupivacaine up to 21.4 mg. Tolerability was variable because of motor weakness. Given that all intrathecal local anesthetics may be neurotoxic, caution must be exercised if high concentrations and daily doses are to be delivered over prolonged periods. PMID- 21029353 TI - "They don't want anything to do with you": patient views of primary care management of chronic pain. AB - OBJECTIVE: Chronic pain is one of the most frequent complaints of patients in primary care, yet both patients and providers report low satisfaction with chronic pain care. This study was designed to explore the views held by a diverse sample of patients with chronic pain complaints about their care experiences to identify ways to improve care. DESIGN: Qualitative analysis of 17 patient focus groups (size 3-7 participants). Groups used structured questions and were tape recorded, transcribed, and coded using qualitative software. Eleven groups were conducted in English, six groups in Spanish. PATIENTS: Convenience sample of 72 adult patients (68% female, 44% Latino, mean age=48.1 years) recruited from four diverse primary care practices in Central Massachusetts. RESULTS: Across all 17 groups, and all gender, ethnicity, and age groups, most patients reported suboptimal interactions with their providers when seeking care for chronic pain. Subjects acknowledged feeling disrespected and distrusted, suspected of drug seeking, and having their symptoms dismissed as trivial and/or not warranting medical care. Patients reported more satisfaction when they felt a provider listened to them, trusted them, was accessible to address pain concerns between visits, and used patient-centered approaches to establish goals and treatment plans. Patients also recommended some management techniques related to the chronic disease management model to improve pain care. CONCLUSIONS: Implementing patient-centered approaches in caring for individuals with chronic pain and using principles drawn from the chronic disease management model to improve care systems may improve both patient and provider satisfaction with chronic pain care. PMID- 21029354 TI - Associations between heat pain perception and opioid dose among patients with chronic pain undergoing opioid tapering. AB - OBJECTIVE: The purpose of this study was to investigate the associations between morphine equivalent dose and heat pain (HP) perception in patients with chronic pain undergoing opioid tapering in the context of a multidisciplinary rehabilitation program. DESIGN: Prospective design. SETTING: Multidisciplinary pain rehabilitation center. PATIENTS: The cohort included 109 patients using opioids (female 52%) who met inclusion criteria, and were consecutively admitted from March 2007 to June 2008. INTERVENTION: Three-week outpatient multidisciplinary rehabilitation program that incorporates opioid tapering. OUTCOME MEASURES: Using a standardized quantitative sensory test (QST) method of levels, standardized values of HP perception were obtained one day following program admission and following completion of the opioid taper at program dismissal. RESULTS: At admission, the mean morphine equivalent dose was 192 mg/day. Univariate linear regression analysis showed that greater baseline morphine equivalent dose was associated (P = 0.040) with lower, or more hyperalgesic, values of HP 5-0.5, which is a standardized measure of HP perception. The dose dependent association retained significance (P = 0.029) after adjusting for pain severity, pain duration and pain diagnosis. Tapering of greater morphine equivalent dosages was associated (P = 0.001) with lower values of HP 5-0.5. The association retained significance (P = 0.001) after adjusting for pain severity, pain duration, pain diagnosis, opioid withdrawal symptoms, and time between completion of the taper and performance of the dismissal QST. CONCLUSION: The use of a validated QST method of levels and standardized values of HP 5-0.5 may expand the methodological approaches available for investigating the clinical effects of opioids on HP perception. PMID- 21029355 TI - Effect of provision of the NHS NPSA oral anticoagulant therapy patient information pack upon patients' knowledge and anticoagulant control. PMID- 21029356 TI - The role of hepatocyte nuclear factor 4alpha in regulating mouse hepatic anticoagulation and fibrinolysis gene transcript levels. PMID- 21029357 TI - Short-term exposure to particulate matter induces arterial but not venous thrombosis in healthy mice. AB - BACKGROUND: Epidemiological findings suggest an association between exposure to particulate matter (PM) and venous thrombo-embolism. OBJECTIVES: To investigate arterial vs. venous thrombosis, inflammation and coagulation in mice, (sub)acutely exposed to two types of PM. METHODS: Various doses (25, 100 and 200 MUg per animal) of urban particulate matter (UPM) or diesel exhaust particles (DEP) were intratracheally (i.t.) instilled in C57Bl6/n mice and several endpoints measured at 4, 10 and 24 h. Mice were also repeatedly exposed to 100 MUg per animal on three consecutive days with endpoints measured 24 h after the last instillation. RESULTS: Exposure to 200 MUg per mouse UPM enhanced arterial thrombosis, but neither UPM nor DEP significantly enhanced venous thrombosis. Both types of PM induced dose-dependent increases in broncho-alveolar lavage fluid (BALF) total cell numbers (mainly neutrophils) and cytokines (IL-6, KC, MCP 1, RANTES, MIP-1alpha), with peaks at 4 h and overall higher values for UPM than for DEP. Systemic inflammation was limited to increased serum IL-6 levels, 4 h after UPM. Both types of PM induced similar and dose-dependent but modest increases in factor (F)VII, FVIII and fibrinogen. Three repeated instillations did not or only modestly enhance the proinflammatory and procoagulant status. CONCLUSIONS: Compared with DEP, UPM induced more pronounced pulmonary inflammation, but both particle types triggered similar and mild short-term systemic effects. Hence, acute exposure to PM triggers activation of primary hemostasis in the mouse, but no substantial secondary hemostasis activation, resulting in arterial but not venous thrombogenicity. PMID- 21029358 TI - Impact on venous thrombosis risk of newly discovered gene variants associated with FVIII and VWF plasma levels. PMID- 21029359 TI - A comparison of risk stratification schemes for stroke in 79,884 atrial fibrillation patients in general practice. AB - BACKGROUND: Anticoagulation management of patients with atrial fibrillation (AF) should be tailored individually on the basis of ischemic stroke risk. The objective of this study was to compare the predictive ability of 15 published stratification schemes for stroke risk in actual clinical practice in the UK. METHODS: AF patients aged >= 18 years in the General Practice Research Database, which contains computerized medical records, were included. The c-statistic was estimated to determine the predictive ability for stroke for each scheme. Outcomes included stroke, hospitalizations for stroke, and death resulting from stroke (as recorded on death certificates). RESULTS: The study cohort included 79,844 AF patients followed for an average of 4 years (average of 2.4 years up to the start of warfarin therapy). All risk schemes had modest discriminatory ability in AF patients, with c-statistics for predicting events ranging from 0.55 to 0.69 for strokes recorded by the general practitioner or in hospital, from 0.56 to 0.69 for stroke hospitalizations, and from 0.56 to 0.78 for death resulting from stroke as reported on death certificates. The proportion of patients assigned to individual risk categories varied widely across the schemes, with the proportion categorized as moderate risk ranging from 12.7% (CHA(2) DS(2) VASc) to 61.5% (modified CHADS(2)). Low-risk subjects were truly low risk (with annual stroke events < 0.5%) with the modified CHADS(2), National Institute for Health and Clinical Excellence and CHA(2) DS(2) -VASc schemes. CONCLUSION: Current published risk schemes have modest predictive value for stroke. A new scheme (CHA(2) DS(2) -VASc) may discriminate those at truly low risk and minimize classification of subjects as intermediate/moderate risk. This approach would simplify our approach to stroke risk stratification and improve decision-making for thromboprophylaxis in patients with AF. PMID- 21029360 TI - Human C-reactive protein enhances thrombus formation after neointimal balloon injury in transgenic rabbits. AB - BACKGROUND: High plasma levels of C-reactive protein (CRP) constitute a powerful predictive marker of cardiovascular events. Several lines of evidence suggest that CRP has prothrombogenic effects. However, whether CRP directly participates in the pathogenesis of thrombosis in vivo has not been fully clarified. OBJECTIVE: To test whether human CRP (hCRP) affects arterial thrombus formation after balloon injury of smooth muscle cell (SMC)-rich or macrophage-rich neointima. METHODS: We compared the susceptibility of transgenic (Tg) rabbits expressing hCRP (46.21 +/- 13.85 mg L(-1), n = 22) and non-Tg rabbits to arterial thrombus formation after balloon injury of SMC-rich or macrophage-rich neointima. RESULTS: Thrombus size on SMC-rich or macrophage-rich neointima was significantly increased, and was accompanied by an increase in fibrin content in hCRP-Tg rabbits, as compared with non-Tg rabbits. Thrombus size did not significantly differ between SMC-rich and macrophage-rich neointima in hCRP-Tg rabbits. Tissue factor (TF) mRNA expression and activity in these neointimal lesions were significantly increased in hCRP-Tg rabbits as compared with non-Tg rabbits. The degree of CRP deposition correlated with the elevated TF expression and thrombus size on injured neointima. In addition, hCRP isolated from hCRP-Tg rabbit plasma induced TF mRNA expression and activity in rabbit cultured vascular SMCs. CONCLUSIONS: These results suggest that elevated plasma hCRP levels promote thrombus formation on injured SMC-rich neointima by enhancing TF expression, but have no additive effects in macrophage-rich neointima. PMID- 21029361 TI - An alphaIIb mutation in patients with Glanzmann thrombasthenia located in the N terminus of blade 1 of the beta-propeller (Asn2Asp) disrupts a calcium binding site in blade 6. AB - BACKGROUND: Studies of Glanzmann thrombasthenia (GT)-causing mutations has generated invaluable information on the formation and function of integrin alphaIIbbeta(3). OBJECTIVE: To characterize the mutation in four siblings of an Israeli Arab family affected by GT, and to analyze the relationships between the mutant protein structure and its function using artificial mutations. METHODS AND RESULTS: Sequencing disclosed a new A97G transversion in the alphaIIb gene predicting Asn2Asp substitution at blade 1 of the beta-propeller. Alignment with other integrin alpha subunits revealed that Asn2 is highly conserved. No surface expression of alphaIIbbeta(3) was found in patients' platelets and baby hamster kidney (BHK) cells transfected with mutated alphaIIb and WT beta(3). Although the alphaIIbbeta(3) was formed, the mutation impaired its intracellular trafficking. Molecular dynamics simulations and modeling of the alphaIIbbeta(3) crystal indicated that the Asn2Asp mutation disrupts a hydrogen bond between Asn2 and Leu366 of a calcium binding domain in blade 6, thereby impairing calcium binding that is essential for intracellular trafficking of alphaIIbbeta(3). Substitution of Asn2 to uncharged Ala or Gln partially decreased alphaIIbbeta(3) surface expression, while substitution by negatively or positively charged residues completely abolished surface expression. Unlike alphaIIbbeta(3), alphaVbeta(3) harboring the Asn2Asp mutation was surface expressed by transfected BHK cells, which is consistent with the known lower sensitivity of alphaVbeta(3) to calcium chelation compared with alphaIIbbeta(3). CONCLUSION: The new GT causing mutation highlights the importance of calcium binding domains in the beta-propeller for intracellular trafficking of alphaIIbbeta(3). The mechanism by which the mutation exerts its deleterious effect was elucidated by molecular dynamics. PMID- 21029362 TI - Internalization of microparticles by endothelial cells promotes platelet/endothelial cell interaction under flow. AB - BACKGROUND: Microparticles (MPs) released by activated or apoptotic cells increase in number in the blood of subjects with vascular or metabolic diseases and may contribute to thrombotic complications. OBJECTIVES: In this study, we investigated whether MPs promoted platelet recruitment to endothelial cells in flow conditions, and by which mechanism. METHODS: Human umbilical vein endothelial cells (HUVECs) grown in microslide perfusion chambers were exposed to MPs prepared in vitro from HUVECs, monocytes or platelets. RESULTS: Videomicroscopy of DIOC-labelled blood perfused at arterial rate on human umbilical vein ECs demonstrated that, irrespective of their cell origin, MPs promoted the formation of platelet strings at the surface of HUVECs. This platelet/endothelial cell interaction was dependent on von Willebrand factor (VWF) expression at the HUVEC surface and involved Glycoprotein Ib and P selectin. Interestingly, HUVECs internalized MPs within a few hours through a process involving anionic phospholipids, lactadherin and alphavbeta3 integrin. This uptake generated the production of reactive oxygen species via the xanthine/xanthine oxidase system (inhibited by allopurinol and the ROCK inhibitor Y-27632) and the NADPH oxidase (inhibited by SOD). Reactive oxygen species appeared essential for VWF expression at the endothelial cell surface and subsequent platelet/endothelial cell interaction under flow. The pathophysiological relevance of this process is underlined by the fact that circulating MPs from Type I diabetic patients induced platelet/endothelial cell interaction under flow, with an intensity correlated with the severity of the vasculopathy. PMID- 21029363 TI - Recombinant human tissue factor pathway inhibitor exerts anticoagulant, anti inflammatory and antimicrobial effects in murine pneumococcal pneumonia. AB - BACKGROUND: Streptococcus (S.) pneumoniae is the most common causative pathogen in community-acquired pneumonia and a major cause of sepsis. Recombinant human tissue factor pathway inhibitor (rh-TFPI) attenuates sepsis-induced coagulation and has been evaluated in clinical trials involving patients with sepsis and community-acquired pneumonia. OBJECTIVE: To examine the effect of rh-TFPI on coagulation, inflammation and bacterial outgrowth in S. pneumoniae pneumonia in mice, with or without concurrent antibiotic treatment. METHODS: Pneumonia was induced by intranasal inoculation with S. pneumoniae. Mice were treated with placebo, rh-TFPI, ceftriaxone or rh-TFPI combined with ceftriaxone. Early (8 h) and late (24 h) initiated treatments were evaluated. Samples were obtained 24 or 48 h after infection, for early and late initiated treatment, respectively. In vitro, placebo or rh-TFPI was added to a suspension of S. pneumoniae. RESULTS: Rh TFPI reduced pneumonia-induced coagulation; rh-TFPI with ceftriaxone further attenuated coagulation relative to ceftriaxone alone. Rh-TFPI inhibited accumulation of neutrophils in lung tissue and reduced the levels of several cytokines and chemokines in lungs and plasma in mice not treated with antibiotics; in these animals, rh-TFPI initiated 24 h after infection decreased pulmonary bacterial loads. In vitro, rh-TFPI also inhibited growth of S. pneumoniae. CONCLUSIONS: Therapeutic rh-TFPI attenuates coagulation, inflammation and bacterial growth during pneumococcal pneumonia, whereby the latter two effects only become apparent in the absence of concurrent antibiotic treatment. PMID- 21029364 TI - Laboratory investigation of lupus anticoagulants: mixing studies are sometimes required. PMID- 21029366 TI - Response to 'Clinical outcomes in NSCLC patients with EGFR mutations: pooled analysis'?(Paz-Ares et al., J Cell Mol Med. 2010; 14: 51-69). PMID- 21029365 TI - Fibrotic response in fibroblasts from congenital disorders of glycosylation. AB - Congenital disorders of glycosylation (CDG) are characterized by a generalized underglycosylation of proteins. CDG is associated with multiple symptoms such as psychomotor retardation, hypotonia, hormonal disturbances, liver fibrosis and coagulopathies. The molecular basis of these symptoms is poorly understood considering the large extent of affected glycoproteins. To better understand the cellular responses to protein underglycosylation in CDG, we have investigated the differences in gene expression between healthy control and CDG fibroblasts by transcriptome comparison. This analysis revealed a strong induction of several genes encoding components of the extracellular matrix, such as collagens, COMP, IGFBP5 and biglycan. The extent of this response was confirmed at the protein level by showing increased production of collagen type-I for example. This fibrotic response of CDG fibroblasts was not paralleled by a differentiation to myofibroblasts and by increased TGF-beta signalling. We could show that the addition of recombinant IGFBP5, one of the induced proteins in CDG, to healthy control fibroblasts increased the production of collagen type-I to levels similar to those found in CDG fibroblasts. The fibrotic response identified in CDG fibroblasts may account for the elevated tissue fibrosis, which is often encountered in CDG patients. PMID- 21029367 TI - The reconstruction of lung alveolus-like structure in collagen matrigel/microcapsules scaffolds in vitro. AB - This study attempted to use collagen-Matrigel as extracellular matrix (ECM) to supply cells with three-dimensional (3D) culture condition and employ alginate poly-l-lysine-alginate (APA) microcapsules to control the formation of alveolus like structure in vitro. We tested mice foetal pulmonary cells (FPCs) by immunohistochemistry after 2D culture. The alveolus-like structure was reconstructed by seeding FPCs in collagen-Matrigel mixed with APA microcapsules 1.5 ml. A self-made mould was used to keep the structure from contraction. Meanwhile, it provided static stretch to the structure. After 7, 14 and 21 days of culture, the alveolus-like structure was analysed histologically and immunohistochemically, or by scanning transmission electron microscopy (TEM). We also observed these structures under inverted phase contrast microscope. The expression of pro-surfactant protein C (SpC) was detected by reverse transcription-polymerase chain reaction (RT-PCR). We obtained fibroblasts, epithelial cells and alveolar type II (AE2) cells in FPCs. In the reconstructed structure, seeding cells surrounding the APA microcapsules constructed alveolus like structures, the size of them ranges from 200 to 300 MUm. In each reconstructed lung tissue sheet, microcapsules had integrity. Pan-cytokeratin, vimentin and SpC positive cells were observed in 7- and 14-day cultured structures. TEM showed lamellar bodies of AE2 cells in the reconstructed tissues whereas RT-PCR expressed SpC gene. Primary mice FPCs could form alveolus-like structures in collagen-Matrigel/APA microcapsules engineered scaffolds, which could maintain a differentiated state of AE2 cells. PMID- 21029368 TI - Pre-clinical and clinical significance of heparanase in Ewing's sarcoma. AB - Heparanase is an endoglycosidase that specifically cleaves heparan sulphate side chains of heparan sulphate proteoglycans, activity that is strongly implicated in cell migration and invasion associated with tumour metastasis, angiogenesis and inflammation. Heparanase up-regulation was documented in an increasing number of human carcinomas, correlating with reduced post-operative survival rate and enhanced tumour angiogenesis. Expression and significance of heparanase in human sarcomas has not been so far reported. Here, we applied the Ewing's sarcoma cell line TC71 and demonstrated a potent inhibition of cell invasion in vitro and tumour xenograft growth in vivo upon treatment with a specific inhibitor of heparanase enzymatic activity (compound SST0001, non-anticoagulant N-acetylated, glycol split heparin). Next, we examined heparanase expression and cellular localization by immunostaining of a cohort of 69 patients diagnosed with Ewing's sarcoma. Heparanase staining was noted in all patients. Notably, heparanase staining intensity correlated with increased tumour size (P = 0.04) and with patients' age (P = 0.03), two prognostic factors associated with a worse outcome. Our study indicates that heparanase expression is induced in Ewing's sarcoma and associates with poor prognosis. Moreover, it encourages the inclusion of heparanase inhibitors (i.e. SST0001) in newly developed therapeutic modalities directed against Ewing's sarcoma and likely other malignancies. PMID- 21029369 TI - The relationship between early embryo development and tumourigenesis. AB - With the recent substantial progress in developmental biology and cancer biology, the similarities between early embryo development and tumourigenesis, as well as the important interaction between tumours and embryos become better appreciated. In this paper, we review in detail the embryonic origin of tumour, and the similarities between early embryo development and tumourigenesis with respect to cell invasive behaviours, epigenetic regulation, gene expression, protein profiling and other important biological behaviours. Given an improved understanding of the relationship between early embryo development and tumourigenesis, now we have better and broader resources to attack cancer from the perspective of developmental biology and develop next generation of prognostic and therapeutic approaches for this devastating disease. PMID- 21029370 TI - Obestatin as a regulator of adipocyte metabolism and adipogenesis. AB - The role of obestatin, a 23-amino-acid peptide encoded by the ghrelin gene, on the control of the metabolism of pre-adipocyte and adipocytes as well as on adipogenesis was determined. For in vitro assays, pre-adipocyte and adipocyte 3T3 L1 cells were used to assess the obestatin effect on cell metabolism and adipogenesis based on the regulation of the key enzymatic nodes, Akt and AMPK and their downstream targets. For in vivo assays, white adipose tissue (WAT) was obtained from male rats under continuous subcutaneous infusion of obestatin. Obestatin activated Akt and its downstream targets, GSK3alpha/beta, mTOR and S6K1, in 3T3-L1 adipocyte cells. Simultaneously, obestatin inactivated AMPK in this cell model. In keeping with this, ACC phosphorylation was also decreased. This fact was confirmed in vivo in white adipose tissue (omental, subcutaneous and gonadal) obtained from male rats under continuous sc infusion of obestatin (24 and 72 hrs). The relevance of obestatin as regulator of adipocyte metabolism was supported by AS160 phosphorylation, GLUT4 translocation and augment of glucose uptake in 3T3-L1 adipocyte cells. In contrast, obestatin failed to modify translocation of fatty acid transporters, FATP1, FATP4 and FAT/CD36, to plasma membrane. Obestatin treatment in combination with IBMX and DEX showed to regulate the expression of C/EBPalpha, C/EBPbeta, C/EBPdelta and PPARgamma promoting adipogenesis. Remarkable, preproghrelin expression, and thus obestatin expression, increased during adipogenesis being sustained throughout terminal differentiation. Neutralization of endogenous obestatin secreted by 3T3-L1 cells by anti-obestatin antibody decreased adipocyte differentiation. Furthermore, knockdown experiments by preproghrelin siRNA supported that obestatin contributes to adipogenesis. In summary, obestatin promotes adipogenesis in an autocrine/paracrine manner, being a regulator of adipocyte metabolism. These data point to a putative role in the pathogenesis of metabolic syndrome. PMID- 21029371 TI - Gata4 and Sp1 regulate expression of the erythropoietin receptor in cardiomyocytes. AB - Experimental studies indicate significant cardioprotective effects of recombinant erythropoietin (Epo) by binding to the Epo receptor (EpoR) and by inducing various molecular mechanisms, including activation of Gata4, a transcription factor that induces anti-apoptotic genes. However, specific molecular mechanisms of EpoR regulation in cardiomyocytes are unknown. We identified a 774 bp regulatory domain in the EpoR 5' flanking region by reporter gene assays in murine HL-1 cardiomyocytes. The binding sites for Gata and Sp transcription factors both significantly contributed to EpoR promoter activity. DNA-binding studies (EMSA and ChIP assays) identified Gata4 and Sp1 as EpoR promoter-binding proteins in HL1 cardiomyocytes. Although Sp1 alone stimulates EpoR only slightly, forced expression of Gata4 significantly induced EpoR mRNA expression. In addition, knockdown of Gata4 (but also of Sp1) resulted in a significant decrease of EpoR transcript levels in HL-1 cardiomyocytes. Cumulative in vitro data suggest that function of the Sp1 site is essential for the Gata4-mediated transcription. In vivo, analysis of transgenic mice expressing an inducible small hairpin RNA against Gata4 confirmed suppression of EpoR expression in the heart. Treating mice with high-dose doxorubicin not only resulted in Gata4 protein depletion, but also down-regulated EpoR, followed by up-regulation of EpoR transcripts when Gata4 levels recovered. In conclusion, we identified Gata4 as novel regulator of EpoR transcription in cardiomyocytes. In models of cardiac injury, down-regulation of Gata4 or Sp1 may limit the accessibility of the EpoR for binding of erythropoiesis-stimulating agents (ESA). Thereby our data underline the essential role of Gata4 in mediating cardioprotective effects. PMID- 21029372 TI - MicroRNA-107, an oncogene microRNA that regulates tumour invasion and metastasis by targeting DICER1 in gastric cancer. AB - MicroRNAs are small non-coding RNA molecules that control expression of target genes. Previous studies showed that microRNA-107 (miR-107) is overexpressed in gastric cancer tissues compared with the matched normal tissues. However, it remains largely unclear as to how miR-107 exerts its function and modulates the malignant phenotypes of gastric cancer, because our understanding of miR-107 signalling pathways is limited. In this study, we demonstrate that miR-107 is frequently up-regulated in gastric cancers and its overexpression is significantly associated with gastric cancer metastasis. Furthermore, silencing the expression of miR-107 could inhibit gastric cancer cell migration and invasion in vitro and in vivo. Subsequent investigation characterized DICER1 as a direct target of miR-107. Up-regulation of DICER1 resulted in a dramatic reduction of in vitro migration, invasion, in vivo liver metastasis of nude mice, which is similar to that occurs with the silencing of miR-107, indicating that DICER1 functions as a metastasis suppressor in gastric cancer. Furthermore, the restoration of DICER1 can inhibit miR-107-induced gastric cancer cell invasion and metastasis. In conclusion, our results suggested that miR-107, an oncogene miRNA promoting gastric cancer metastasis through down-regulation of DICER1. Inhibition of miR-107 or restoration of DICER1 may represent a new potential therapeutic target for gastric cancer treatment. PMID- 21029373 TI - Circulating stem cell vary with NYHA stage in heart failure patients. AB - We have investigated the blood levels of sub-classes of stem cells (SCs) [mesenchymal stem cells (MSCs), haematopoietic stem cells (HSCs), endothelial progenitor cells/circulating endothelial cells (EPCs/CECs) and tissue-committed stem cells (TCSCs)] in heart failure (HF) patients at different stage of pathology and correlated it with plasmatic levels of proangiogenic cytokines. Peripheral blood level of SCs were analysed in 97 HF patients (24 in NYHA class I, 41 in class II, 17 in class III and 15 in class IV) and in 23 healthy controls. Plasmatic levels of PDGF-BB, bFGF, HGF, vascular endothelial growth factor (VEGF), SDF-1alpha, TNF-alpha and NTproBNP were also measured. Compared with healthy individuals, MSC, and in particular the sub-classes CD45(-) CD34(-) CD90(+) , CD45(-) CD34(-) CD105(+) and CD45(-) CD34(-) CXCR4(+) were significantly enhanced in NYHA class IV patients (16.8-, 6.4- and 2.7-fold, respectively). Level of CD45(-) CD34(-) CD90(+) CXCR4(+) cells progressively increased from class II to class IV (fold increases compared with controls: 8.5, 12 and 21.5, respectively). A significant involvement of CXCR4(+) subpopulation of HSC (CD45(+) CD34(+) CD90(+) CXCR4(+) , 1.4 versus 13.3 cells/MUl in controls and NYHA class III patients, respectively) and TCSC (CD45(-) CD34(+) CXCR4(+) , 1.5 cells/ MUl in controls versus 12.4 and 28.6 cells/MUl in NYHA classes II and IV, respectively) were also observed. All tested cytokines were enhanced in HF patients. In particular, for PDGF-BB and SDF-1alpha we studied specific ligand/receptors pairs. Interestingly, the first one positively correlated with TCSCs expressing PDGFR (r = 0.52, P = 0.001), whereas the second one correlated with TCSCs (r = 0.34, P = 0.005) and with MSCs CD90(+) expressing CXCR4 (r = 0.39, P = 0.001). HF is characterized by the increase in the circulating levels of different MSC, HSC, EPC and TCSC subsets. Both the entity and kinetic of this process varied in distinct cell subsets. Specifically, differently from HSCs and EPCs/CECs, MSCs and TCSCs significantly increased with the progression of the disease, suggesting a possible distinct role of these cells in the pathophysiology of HF. PMID- 21029374 TI - Direct contact of umbilical cord blood endothelial progenitors with living cardiac tissue is a requirement for vascular tube-like structures formation. AB - The umbilical cord blood derived endothelial progenitor cells (EPCs) contribute to vascular regeneration in experimental models of ischaemia. However, their ability to participate in cardiovascular tissue restoration has not been elucidated yet. We employed a novel coculture system to investigate whether human EPCs have the capacity to integrate into living and ischaemic cardiac tissue, and participate to neovascularization. EPCs were cocultured with either living or ischaemic murine embryonic ventricular slices, in the presence or absence of a pro-angiogenic growth factor cocktail consisting of VEGF, IGF-1, EGF and bFGF. Tracking of EPCs within the cocultures was performed by cell transfection with green fluorescent protein or by immunostaining performed with anti-human vWF, CD31, nuclei and mitochondria antibodies. EPCs generated vascular tube-like structures in direct contact with the living ventricular slices. Furthermore, the pro-angiogenic growth factor cocktail reduced significantly tubes formation. Coculture of EPCs with the living ventricular slices in a transwell system did not lead to vascular tube-like structures formation, demonstrating that the direct contact is necessary and that the soluble factors secreted by the living slices were not sufficient for their induction. No vascular tubes were formed when EPCs were cocultured with ischaemic ventricular slices, even in the presence of the pro-angiogenic cocktail. In conclusion, EPCs form vascular tube-like structures in contact with living cardiac tissue and the direct cell-to-cell interaction is a prerequisite for their induction. Understanding the cardiac niche and micro-environmental interactions that regulate EPCs integration and neovascularization are essential for applying these cells to cardiovascular regeneration. PMID- 21029375 TI - OPRM1 gene variants modulate amphetamine-induced euphoria in humans. AB - The MU-opioid receptor is involved in the rewarding effects of not only opioids like morphine but also psychostimulants like amphetamine. This study aimed to investigate associations between subjective response to amphetamine and genetic polymorphisms and haplotypes in the MU-opioid receptor including the exonic variant rs1799971 (Asp40Asn). One hundred and sixty-two Caucasian volunteers participated in three sessions receiving either placebo or d-amphetamine (10 and 20 mg). Associations between levels of self-reported Euphoria, Energy and Stimulation [Addiction Research Center Inventory 49-item questionnaire (ARCI-49)] after d-amphetamine ingestion and polymorphisms in OPRM1 were investigated. The intronic single nucleotide polymorphisms (SNPs) rs510769 and rs2281617 were associated with significantly higher ratings of Euphoria, Energy and Stimulation after 10 mg amphetamine. Feelings of Euphoria, Energy and Stimulation were also found to be associated with a two-SNP haplotype formed with rs1799971 and rs510769 and a three-SNP haplotype formed with rs1918760, rs2281617 and rs1998220. These results support the hypothesis that genetic variability in the MU-opioid receptor gene influences the subjective effects of amphetamine and may suggest new strategies for prevention and treatment of psychostimulant abuse. PMID- 21029377 TI - Quality of life in health care of non-melanoma skin cancer - results of a pilot study. AB - BACKGROUND: Modern patient-oriented medicine increasingly involves psychosocial aspects of disease processes in therapy evaluations. We conducted a pilot study on the implementation of a suitable device assessing the quality of life of patients with non-melanoma skin cancer (NMSC) in clinical routine. PATIENTS AND METHODS: 52 patients with NMSC were asked to fill out the German version of the Dermatology Life Quality Index (DLQI) by A.Y. Finlay. Additionally, one-third of the patients were evaluated by the treating physicians. RESULTS: The questionnaire was well-accepted and completed within a few minutes. Less than 1 % values were missing with respect to individual items. 31 % of patients experienced a moderate to strong impairment of the quality of life. This impairment involved symptoms, emotions, everyday activities, and leisure activities, whereas work and school were of minor importance. The variables age, gender, and diagnosis were of little importance. CONCLUSIONS: The limited number of publications available necessitates a step-wise introduction of this topic into the German literature. Data on quality of life could be relevant for the inclusion of NMSC onto the list of occupational diseases in occupations with high UV exposure. Sufficient data have to be generated in follow-up studies of longitudinal design that are based on the present pilot study. PMID- 21029376 TI - Serine racemase deletion disrupts memory for order and alters cortical dendritic morphology. AB - There is substantial evidence implicating N-methyl-D-aspartate receptors (NMDARs) in memory and cognition. It has also been suggested that NMDAR hypofunction might underlie the cognitive deficits observed in schizophrenia as morphological changes, including alterations in the dendritic architecture of pyramidal neurons in the prefrontal cortex (PFC), have been reported in the schizophrenic brain post mortem. Here, we used a genetic model of NMDAR hypofunction, a serine racemase knockout (SR-/-) mouse in which the first coding exon of the mouse SR gene has been deleted, to explore the role of D-serine in regulating cognitive functions as well as dendritic architecture. SR-/- mice exhibited a significantly disrupted representation of the order of events in distinct experiences as showed by object recognition and odor sequence tests; however, SR-/- animals were unimpaired in the detection of novel objects and in spatial displacement, and showed intact relational memory in a test of transitive inference. In addition, SR-/- mice exhibited normal sociability and preference for social novelty. Neurons in the medial PFC of SR-/- mice displayed reductions in the complexity, total length and spine density of apical dendrites. These findings show that D serine is important for specific aspects of cognition, as well as in regulating dendritic morphology of pyramidal neurons in the medial PFC (mPFC). Moreover, they suggest that NMDAR hypofunction might, in part, be responsible for the cognitive deficits and synaptic changes associated with schizophrenia, and highlight this signaling pathway as a potential target for therapeutic intervention. PMID- 21029378 TI - Active and regulatory sites of cytosolic 5'-nucleotidase. AB - Cytosolic 5'-nucleotidase (cN-II), which acts preferentially on 6-hydroxypurine nucleotides, is essential for the survival of several cell types. cN-II catalyses both the hydrolysis of nucleotides and transfer of their phosphate moiety to a nucleoside acceptor through formation of a covalent phospho-intermediate. Both activities are regulated by a number of phosphorylated compounds, such as diadenosine tetraphosphate (Ap4A), ADP, ATP, 2,3-bisphosphoglycerate (BPG) and phosphate. On the basis of a partial crystal structure of cN-II, we mutated two residues located in the active site, Y55 and T56. We ascertained that the ability to catalyse the transfer of phosphate depends on the presence of a bulky residue in the active site very close to the aspartate residue that forms the covalent phospho-intermediate. The molecular model indicates two possible sites at which adenylic compounds may interact. We mutated three residues that mediate interaction in the first activation site (R144, N154, I152) and three in the second (F127, M436 and H428), and found that Ap4A and ADP interact with the same site, but the sites for ATP and BPG remain uncertain. The structural model indicates that cN-II is a homotetrameric protein that results from interaction through a specific interface B of two identical dimers that have arisen from interaction of two identical subunits through interface A. Point mutations in the two interfaces and gel-filtration experiments indicated that the dimer is the smallest active oligomerization state. Finally, gel-filtration and light scattering experiments demonstrated that the native enzyme exists as a tetramer, and no further oligomerization is required for enzyme activation. PMID- 21029379 TI - Marking territory-now and for the future. PMID- 21029380 TI - Future sexual medicine physiological treatment targets. AB - INTRODUCTION: Sexual function in men and women incorporates physiologic processes and regulation of the central and peripheral nervous systems, the vascular system, and the endocrine system. There is need for state-of-the-art information as there is an evolving research understanding of the underlying molecular biological factors and mechanisms governing sexual physiologic functions. AIM: To develop an evidence-based, state-of-the-art consensus report on the current knowledge of the major cellular and molecular targets of biologic systems responsible for sexual physiologic function. METHODS: State-of-the-art knowledge representing the opinions of seven experts from four countries was developed in a consensus process over a 2-year period. MAIN OUTCOME MEASURES: Expert opinion was based on the grading of evidence-based medical literature, widespread internal committee discussion, public presentation, and debate. RESULTS: Scientific investigation in this field is needed to increase knowledge and foster development of the future line of treatments for all forms of biological-based sexual dysfunction. This article addresses the current knowledge of the major cellular and molecular targets of biological systems responsible for sexual physiologic function. Future treatment targets include growth factor therapy, gene therapy, stem and cell-based therapies, and regenerative medicine. CONCLUSIONS: Scientific discovery is critically important for developing new and increasingly effective treatments in sexual medicine. Broad physiologic directions should be vigorously explored and considered for future management of sexual disorders. PMID- 21029381 TI - Education in sexual medicine: proceedings from the international consultation in sexual medicine, 2009. AB - INTRODUCTION: Sexual problems in men and women are common; and physicians endorse many barriers to addressing these issues, including lack of knowledge about the diagnosis and management of sexual problems and inadequate training in sexual health communication and counseling. AIM: To update the recommendations published in 2004, from the International Consultation on Sexual Medicine (ICSM) relevant to the educational aspects of sexual health in undergraduate, graduate, and postgraducate medical education. METHODS: A third international consultation in collaboration with the major sexual health organizations assembled over 186 multidisciplinary experts from 33 countries into 25 committees. Three experts from three countries contributed to this committee's review of Education in Sexual Medicine. MAIN OUTCOME MEASURE: Expert opinion was based on a comprehensive review of the medical literature, committee discussion, public presentation, and debate. RESULTS: A comprehensive review about the current state of undergraduate, graduate, and postgraduate sexual health education worldwide is provided. Recommendations about ideal sexual health curricula across training levels are provided. Best methods for achieving optimal training approaches to sexual health communication and interviewing, clinical skills and management, and counseling are described. CONCLUSIONS: Current sexual health education for undergraduate and practicing physicians is inadequate to meet the advancing science and technology and increasing patient demand for high-quality sexual health care. There is a need for enhanced training in medical institutions responsible for physician sexual health training worldwide. Future training programs at all levels of medical education should incorporate standardized measures of sexual health clinical skills acquisition and assessments of the impact on patient outcomes into the design of educational initiatives. PMID- 21029382 TI - Background and considerations on the National Survey of Sexual Health and Behavior (NSSHB) from the investigators. PMID- 21029383 TI - Sexual behavior in the United States: results from a national probability sample of men and women ages 14-94. AB - INTRODUCTION: Despite a demonstrated relationship between sexual behaviors and health, including clinical risks, little is known about contemporary sexual behavior. AIMS: To assess the rates of sexual behavior among adolescents and adults in the United States. METHODS: We report the recent (past month, past year) and lifetime prevalence of sexual behaviors in a nationally representative probability sample of 5,865 men and women ages 14 to 94 in the United States (2,936 men, 2,929 women). MAIN OUTCOME MEASURES: Behaviors assessed included solo masturbation, partnered masturbation, giving and receiving oral sex, vaginal intercourse, and anal intercourse. RESULTS: Masturbation was common throughout the lifespan and more common than partnered sexual activities during adolescence and older age (70+). Although uncommon among 14- to 15-year olds, in the past year 18.3% of 16- to 17-year-old males and 22.4% of 16- to 17-year-old females performed oral sex with an other-sex partner. Also in the past year, more than half of women and men ages 18 to 49 engaged in oral sex. The proportion of adults who reported vaginal sex in the past year was highest among men ages 25-39 and for women ages 20-29, then progressively declined among older age groups. More than 20% of men ages 25-49 and women ages 20-39 reported anal sex in the past year. Same-sex sexual behaviors occurring in the past year were uncommonly reported. CONCLUSIONS: Men and women engage in a diverse range of solo and partnered sexual behaviors throughout the life course. The rates of contemporary sexual behavior provided in this report will be valuable to those who develop, implement, and evaluate programs that seek to improve societal knowledge related to the prevalence of sexual behaviors and to sexual health clinicians whose work to improve sexual health among the population often requires such rates of behavior. PMID- 21029384 TI - Condom use rates in a national probability sample of males and females ages 14 to 94 in the United States. AB - INTRODUCTION: Given the efficacy of latex condoms for preventing pregnancy, HIV, and most STI, their promotion remains central to global sexual health efforts. To inform the development of accurate and appropriately-targeted interventions, there is a need for contemporary condom use rates among specific populations. AIMS: The purpose of this study was to establish rates of condom use among sexually active individuals in the U.S. population. METHODS: Data were collected via a national probability sample of 5,865 U.S. adolescents and adults aged 14 to 94 years. MAIN OUTCOME MEASURES: Condom use was assessed during the most recent partnered vaginal or anal sexual event and over the past 10 vaginal and anal intercourse events. RESULTS: Condom use by men during past 10 vaginal intercourse events was slightly higher (21.5%) than that reported by women (18.4%), and consistent with rates of condom use reported during most recent vaginal intercourse by men (24.7%) and women (21.8%). Adolescent men reported condom use during 79.1% of the past 10 vaginal intercourse events, adolescent women reported use during 58.1% of the same. Condom use during past 10 anal intercourse events was higher among men (25.8%) than women (13.2%); the same was observed for most recent anal intercourse event (26.5% for insertive men, 44.1% for receptive men, and 10.8% for receptive women). Generally, condom use was highest among unmarried adults, higher among adolescents than adults, and higher among black and Hispanic individuals when compared with other racial groups. CONCLUSION: These data indicate clear trends in condom use across age, gender, relationship status, and race/ethnicity. These contemporary rates of condom use will be helpful to those who lead efforts to increase condom use among individuals who may be at risk for sexually transmitted infections or who desire to prevent pregnancy. PMID- 21029385 TI - Sexual behaviors, relationships, and perceived health status among adult women in the United States: results from a national probability sample. AB - INTRODUCTION: Past surveys of sexual behavior have demonstrated that female sexual behavior is influenced by medical and sociocultural changes. To be most attentive to women and their sexual lives, it is important to have an understanding of the continually evolving sexual behaviors of contemporary women in the United States. AIMS: The purpose of this study, the National Survey of Sexual Health and Behavior (NSSHB), was to, in a national probability survey of women ages 18-92, assess the proportion of women in various age cohorts who had engaged in solo and partnered sexual activities in the past 90 days and to explore associations with participants' sexual behavior and their relationship and perceived health status. Past year frequencies of masturbation, vaginal intercourse, and anal intercourse were also assessed. METHODS: A national probability sample of 2,523 women ages 18 to 92 completed a cross-sectional internet based survey about their sexual behavior. MAIN OUTCOME MEASURES: Relationship status; perceived health status; experience of solo masturbation, partnered masturbation, giving oral sex, receiving oral sex, vaginal intercourse, anal intercourse, in the past 90 days; frequency of solo masturbation, vaginal intercourse, and anal intercourse in the past year. RESULTS: Recent solo masturbation, oral sex, and vaginal intercourse were prevalent among women, decreased with age, and varied in their associations with relationship and perceived health status. Recent anal sex and same-sex oral sex were uncommonly reported. Solo masturbation was most frequent among women ages 18 to 39, vaginal intercourse was most frequent among women ages 18 to 29 and anal sex was infrequently reported. CONCLUSION: Contemporary women in the United States engage in a diverse range of solo and partnered sexual activities, though sexual behavior is less common and more infrequent among older age cohorts. PMID- 21029386 TI - Sexual behaviors, relationships, and perceived health among adult men in the United States: results from a national probability sample. AB - INTRODUCTION: To provide a foundation for those who provide sexual health services and programs to men in the United States, the need for population-based data that describes men's sexual behaviors and their correlates remains. AIMS: The purpose of this study was to, in a national probability survey of men ages 18 94 years, assess the occurrence and frequency of sexual behaviors and their associations with relationship status and health status. METHODS: A national probability sample of 2,522 men aged 18 to 94 completed a cross-sectional survey about their sexual behaviors, relationship status, and health. MAIN OUTCOME MEASURES: Relationship status; health status; experience of solo masturbation, partnered masturbation, giving oral sex, receiving oral sex, vaginal intercourse and anal intercourse, in the past 90 days; frequency of solo masturbation, vaginal intercourse and anal intercourse in the past year. RESULTS: Masturbation, oral intercourse, and vaginal intercourse are prevalent among men throughout most of their adult life, with both occurrence and frequency varying with age and as functions of relationship type and physical health status. Masturbation is prevalent and frequent across various stages of life and for both those with and without a relational partner, with fewer men with fair to poor health reporting recent masturbation. Patterns of giving oral sex to a female partner were similar to those for receiving oral sex. Vaginal intercourse in the past 90 days was more prevalent among men in their late 20s and 30s than in the other age groups, although being reported by approximately 50% of men in the sixth and seventh decades of life. Anal intercourse and sexual interactions with other men were less common than all other sexual behaviors. CONCLUSION: Contemporary men in the United States engage in diverse solo and partnered sexual activities; however, sexual behavior is less common and more infrequent among older age cohorts. PMID- 21029387 TI - Sexual behaviors and condom use at last vaginal intercourse: a national sample of adolescents ages 14 to 17 years. AB - INTRODUCTION: Data on adolescents' sexual and condom use behaviors provides an empirical basis for a range of social, educational, clinical, and public health endeavors. AIMS: This study has two purposes: to describe the recent and lifetime prevalence of a variety of sexual behaviors; and, to describe factors associated with condom use at last penile-vaginal intercourse. METHODS: Data included those from male (N = 414) and female (N = 406) adolescents (ages 14-17 years) from a nationally representative probability sample. Survey items addressed occurrence (past 90 days, past year, lifetime) of solo masturbation, partnered masturbation, oral sex given to a partner, oral sex received from a partner, vaginal intercourse, and anal intercourse. Participants reporting partnered sexual behaviors in the past year completed additional items about condom use, location of sex, partner characteristics, other sexual behaviors, and alcohol or marijuana use at the most recent sexual event. MAIN OUTCOME MEASURES: Adjusted rates (by gender) of sexual behaviors, and characteristics of most recent vaginal sex event as a function of condom use/non-use. RESULTS: Lifetime prevalence of solo masturbation was common for males (80%) and females (48%). Lifetime prevalence of penile-vaginal sex increased with each year of age for both adolescent men and women; however, penile-vaginal sex within the previous 90 days was much less frequently reported. Rates of condom use for penile-vaginal sex were 80% for males and 69% for females. Lifetime anal sex rates were 4.7% for males and 5.5% for females. CONCLUSION: Sexual behavior among adolescents was more prevalent and diverse in older adolescent cohorts. Condom use for penile-vaginal intercourse was reported for a majority of events. PMID- 21029389 TI - Sexual health among U.S. black and Hispanic men and women: a nationally representative study. AB - INTRODUCTION: Little is known about the prevalence of sexual behaviors among the black and Hispanic populations in the United States outside the context of sexual risk and disease transmission in "high-risk" samples. AIM: This study sought to establish current rates of sexual behaviors, sexual health care practices (i.e., experiences with testing and diagnosis of sexually transmitted infections [STIs]), and condom use in a probability sample of black and Hispanic adult men and women in the United States. MAIN OUTCOME MEASURES: Sexual behaviors including solo masturbation, partnered masturbation, receiving oral sex and giving oral sex, vaginal intercourse, and anal intercourse were assessed. Self-reported rates of HIV and other STI testing, and self-reported history of STI diagnosis were examined. Also assessed were rates of condom use during most recent and past 10 vaginal intercourse events. METHODS: Data from a probability sample of 1246 black and Hispanic adults were analyzed to explore sexual behaviors, condom use, and STI testing and diagnosis trends. RESULTS: Masturbation, oral sex, and vaginal intercourse were prevalent among black and Hispanic men and women throughout the life course. Anal intercourse and same-gender sexual activities were less common. Self-reported rates of HIV testing were relatively high but varied by gender across age groups. Similarly, rates of testing for other STI were high and differed by gender across age groups. Overall rates of condom use among black and Hispanic men and women were relatively high and did not appear to be related to a variety of situational factors including location of sexual encounter, relationship status, other contraceptive use, and substance use during sexual activity. CONCLUSION: These data provide a foundation for understanding diverse sexual behaviors, sexual health-care practices, and condom use among the general population of black and Hispanic men and women in the United States. PMID- 21029388 TI - Sexual behaviors, condom use, and sexual health of Americans over 50: implications for sexual health promotion for older adults. AB - INTRODUCTION: In the contemporary U.S., men and women are living longer and healthier lives. As such, many people spend greater portions of their lives as sexually active individuals. Yet, little is known about the myriad of ways that older adults experience their sexual lives. AIM: This study sought to assess the context and frequency of sexual behaviors, condom use, sexual pleasure, and sexual experience of men and women over age 50. METHODS: Information regarding the sexual experiences of a nationally representative sample of men and women over age 50 within the past year was examined. MAIN OUTCOME MEASURES: Sexual behavior over the past year was assessed in relation to several situational and contextual characteristics (e.g., event location, type of partner, health status, condom use). Participants were also asked about their experience (i.e., pleasure, arousal, pain, lubrication/erectile difficulties, and orgasm) during their most recent partnered sexual event. Bivariate or ordinal logistic regression models were used to investigate the relationship of age, health and partner status to sexual frequency and experience. RESULTS: Although sizable proportions (20-30%) of both men and women remained sexually active well into their 80s age was related to a lower likelihood of solo and most partnered sexual behaviors. When controlling for age, relationship status, and health remained significant predictors of select sexual behaviors. The participant's evaluation of their most recent sexual experience in terms of arousal, erectile difficulty, and orgasm all declined with age. Health status was related to men's evaluation of the experience. Relationship status was the most consistent predictor of women's evaluation of the experience. Condom use rates remained low for participants across age groups. CONCLUSION: Many older adults continue be sexually active well into advanced age (80+). Thus, providers need to be attentive to the diverse sexual health needs of older adults. PMID- 21029390 TI - An event-level analysis of the sexual characteristics and composition among adults ages 18 to 59: results from a national probability sample in the United States. AB - INTRODUCTION: Although studies of specific groups of individuals (e.g., adolescents, "high risk" samples) have examined sexual repertoire, little is known, at the population level, about the sexual behaviors that comprise a given sexual encounter. AIM: To assess the sexual behaviors that men and women report during their most recent sexual event; the age, partner and situational characteristics related to that event; and their association with participants' evaluation of the sexual event. METHODS: During March-May 2009, data from a United States probability sample related to the most recent partnered sexual event reported by 3990 adults (ages 18-59) were analyzed. MAIN OUTCOME MEASURES: Measures included sexual behaviors during the most recent partnered sexual event, event characteristics (i.e., event location, alcohol use, marijuana use, and for men, erection medication use), and evaluations of the sexual experience (pleasure, arousal, erection/lubrication difficulty, orgasm). RESULTS: Great diversity exists in the behaviors that occur during a single sexual event by adults, with a total of 41 combinations of sexual behaviors represented across this sample. Orgasm was positively related to the number of behaviors that occurred and age was related to greater difficulty with erections and lubrication. Men whose most recent event was with a relationship partner indicated greater arousal, greater pleasure, fewer problems with erectile function, orgasm, and less pain during the event compared with men whose last event was with a nonrelationship partner. CONCLUSION: Findings demonstrate that adults ages 18 to 59 engage in a diverse range of behaviors during a sexual event and that greater behavior diversity is related to ease of orgasm for both women and men. Although both men and women experience sexual difficulties related to erectile function and lubrication with age, men's orgasm is facilitated by sex with a relationship partner whereas the likelihood of women's orgasm is related to varied sexual behaviors. PMID- 21029391 TI - Condom use during most recent vaginal intercourse event among a probability sample of adults in the United States. AB - INTRODUCTION: Correct and consistent condom use remains the most effective way to reduce sexually transmissible infection/HIV transmission during sex and is a highly effective contraceptive method. Understanding correlates of condom use is vital to public health programs. AIM: To explore sociodemographic, event characteristics, and experiential correlates of condom use at last penile-vaginal intercourse (PVI). METHODS: Survey data were collected from a nationally representative probability sample of adults in the United States as part of the National Survey of Sexual Health and Behavior. MAIN OUTCOME MEASURES: Condom use/non-use at most recent PVI was the main outcome. Logistic regression analyses predicted condom use from sociodemographic variables (i.e., age, education, race/ethnicity, sexual orientation, health status, type of relationship with sexual partner) and event characteristics (i.e., location of sexual encounter, prior intercourse experience with partner, whether partner had other sex partners in the 6 months prior to sex with the participant; other contraceptive use, alcohol use, marijuana use, and for men, erection medication use). Logistic regression analyses examined evaluations of the sexual aspects of the experience (pleasure, arousal, erection/lubrication difficulty, participant orgasm, partner orgasm) in light of condom use. RESULTS: Condom-protected PVI was significantly greater among younger people, blacks and Hispanics, and those having PVI with a nonrelationship partner. Statistically adjusting for these differences, condom use was significantly associated with fewer previous intercourse experiences with the partner and not using other forms of contraception. The sexual aspects of experience were evaluated similarly regardless of whether or not a condom was used. CONCLUSION: Public health programs among youths and minorities may underlie higher condom use rates among these groups. Condom use may be further improved by continuing such programs and also expanding outreach to older persons and whites, suggesting prolonging use as relationships develop, and highlighting that condom use does not necessarily interfere with the sexual experience. PMID- 21029392 TI - Chemosensory function of amphibian skin: integrating epithelial transport, capillary blood flow and behaviour. AB - Terrestrial anuran amphibians absorb water across specialized regions of skin on the posterioventral region of their bodies. Rapid water absorption is mediated by the insertion of aquaporins into the apical membrane of the outermost cell layer. Water moves out of the epithelium via aquaglyceroporins in the basolateral membrane and into the circulation in conjunction with increased capillary blood flow to the skin and aquaporins in the capillary endothelial cells. These physiological responses are activated by intrinsic stimuli relating to the animals' hydration status and extrinsic stimuli relating to the detection of osmotically available water. The integration of these processes has been studied using behavioural observations in conjunction with neurophysiological recordings and studies of epithelial transport. These studies have identified plasma volume and urinary bladder stores as intrinsic stimuli that activate the formation of angiotensin II (AII) to stimulate water absorption behaviour. The coordinated increase in water permeability and capillary blood flow appears to be mediated primarily by sympathetic stimulation of beta adrenergic receptors, although the neurohypopyseal hormone arginine vasotocin (AVT) may also play a role. Extrinsic stimuli relate primarily to the ionic and osmotic properties of hydration sources. Toads avoid NaCl solutions that have been shown to be harmful in acute exposure, approx. 200-250 mm. The avoidance is partially attenuated by amiloride raising the hypothesis that the mechanism for salt detection by toads resembles that for salt taste in mammals that take in water by mouth. In this model, depolarization of the basolateral membrane of taste cells is coupled to afferent neural stimulation. In toad skin we have identified innervation of skin epithelial cells by branches of spinal nerves and measured neural responses to NaCl solutions that elicit behavioural avoidance. These same concentrations produce depolarization of the basolateral membrane in isolated epithelial preparations. As with salt taste in mammals, the neural responses and depolarization of basolateral membrane potential are partially inhibited by amiloride. In addition, toads are more tolerant of sodium gluconate solution which is consistent with the phenomenon in mammalian taste physiology termed the anion paradox in which sodium salts with larger molecular weight anions produce a reduced intensity of salt taste. Finally, toads also avoid concentrated solutions of a non-electrolyte, mannitol, which differs from NaCl solutions in not affecting transepithelial conductance and requires a longer time to depolarize the basolateral membrane. Osmotic stimuli may mediate sensory processes for longer term detection of conditions with low water potential while ionic stimuli are more important for shorter term analysis of rehydration sources. PMID- 21029394 TI - Spectral analysis by XANES reveals that GPNMB influences the chemical composition of intact melanosomes. AB - GPNMB is a unique melanosomal protein. Unlike many melanosomal proteins, GPNMB has not been associated with any forms of albinism, and it is unclear whether GPNMB has any direct influence on melanosomes. Here, melanosomes from congenic strains of C57BL/6J mice mutant for Gpnmb are compared to strain-matched controls using standard transmission electron microscopy and synchrotron-based X-ray absorption near-edge structure analysis (XANES). Whereas electron microscopy did not detect any ultrastructural changes in melanosomes lacking functional GPNMB, XANES uncovered multiple spectral phenotypes. These results directly demonstrate that GPNMB influences the chemical composition of melanosomes and more broadly illustrate the potential for using genetic approaches in combination with nano imaging technologies to study organelle biology. PMID- 21029393 TI - Artificial skin in perspective: concepts and applications. AB - Skin, the largest organ of the human body, is organized into an elaborate layered structure consisting mainly of the outermost epidermis and the underlying dermis. A subcutaneous adipose-storing hypodermis layer and various appendages such as hair follicles, sweat glands, sebaceous glands, nerves, lymphatics, and blood vessels are also present in the skin. These multiple components of the skin ensure survival by carrying out critical functions such as protection, thermoregulation, excretion, absorption, metabolic functions, sensation, evaporation management, and aesthetics. The study of how these biological functions are performed is critical to our understanding of basic skin biology such as regulation of pigmentation and wound repair. Impairment of any of these functions may lead to pathogenic alterations, including skin cancers. Therefore, the development of genetically controlled and well characterized skin models can have important implications, not only for scientists and physicians, but also for manufacturers, consumers, governing regulatory boards and animal welfare organizations. As cells making up human skin tissue grow within an organized three-dimensional (3D) matrix surrounded by neighboring cells, standard monolayer (2D) cell cultures do not recapitulate the physiological architecture of the skin. Several types of human skin recombinants, also called artificial skin, that provide this critical 3D structure have now been reconstructed in vitro. This review contemplates the use of these organotypic skin models in different applications, including substitutes to animal testing. PMID- 21029395 TI - mTOR pathway activation in cutaneous melanoma is associated with poorer prognosis characteristics. PMID- 21029397 TI - Recombinant human arginase inhibits the in vitro and in vivo proliferation of human melanoma by inducing cell cycle arrest and apoptosis. AB - Melanoma has been shown to require arginine for growth, thus providing a potential Achilles' heel for therapeutic exploitation. Our investigations show that arginine depletion, using a recombinant form of human arginase I (rhArg), efficiently inhibits the growth of mammalian melanoma cell lines in vitro. These cell lines are consistently deficient in ornithine transcarbamylase (OTC) expression, correlating with their sensitivity to rhArg. Cell cycle distribution of A375 human melanoma cells treated with rhArg showed a remarkable dual-phase cell cycle arrest in S and G2/M phases, in contrast to the G2/M single-phase arrest observed with arginine deiminase (ADI), another arginine-degrading enzyme. rhArg and ADI both induced substantial apoptosis in A375 cells, accompanied by global modulation of cell cycle- and apoptosis-related transcription. Moreover, PEGylated rhArg dramatically inhibited the growth of A375 and B16 melanoma xenografts in vivo. Our results establish for the first time that (PEGylated) rhArg is a promising candidate for effective melanoma treatment, with fewer safety issues than ADI. Insight into the mechanism behind the antiproliferative activity of rhArg could inform us in designing combination therapies for future clinical trials. PMID- 21029396 TI - Plexin B1 inhibits integrin-dependent pp125FAK and Rho activity in melanoma. AB - Semaphorins are secreted and membrane bound proteins that regulate axon guidance through receptors Plexins and neuropilins. Plexin B1, the Semaphorin 4D receptor, is a recently described tumor suppressor protein for melanoma. We recently showed that Plexin B1 abrogates activation of the oncogenic receptor, c-Met, by its ligand, hepatocyte growth factor (HGF), in melanoma. We have now investigated the effect of Plexin B1 on integrin-dependent pp125(FAK) activation, and the small GTP-binding protein Rho, in melanoma. Integrin receptors and Rho play critical roles in melanoma progression, through regulation of migration, proliferation and apoptosis. We engineered two human melanoma cell lines expressing Plexin B1 and analyzed integrin-dependent migration, integrin-dependent pp125(FAK) activation, and Rho activity. Results show that Plexin B1 abrogates integrin-dependent migration and activation of pp125(FAK). We also show that Rho activity is significantly reduced in cells expressing Plexin B1, and that Plexin B1 suppresses HGF-dependent Rho activation. PMID- 21029398 TI - Immune reactions in benign and malignant melanocytic lesions: lessons for immunotherapy. AB - Spontaneous regression of benign and malignant melanocytic lesions can be a visible sign of immunosurveillance. In this review, we discuss different immune reactions against melanocytic lesions: halo nevus, Meyerson's nevus, regression in melanoma and melanoma-associated depigmentation. These entities present with particular clinical aspects, histology and evolution. In all entities, a melanocyte-specific T-cell reaction has been assumed but a different degree of melanocyte destruction is present. A focus on the immune responses in melanocytic lesions reveals several aspects of an adequate skin immunity and may help to identify the key points in the immune destruction of melanocytes. These insights can add to the knowledge of how to optimize immunotherapeutic strategies in melanoma. PMID- 21029399 TI - Assessment of farmer knowledge of large ruminant health and production in developing village-level biosecurity in northern Lao PDR. AB - The purpose of this study was to determine baseline knowledge and identify knowledge gaps of farmers on biosecurity, risk of transmission of transboundary diseases and large ruminant health and production in three provinces of northern Laos, Hua Phan (HP), Luang Prabang (LPB) and Xieng Khoung (XK). The survey was conducted in six villages that are project sites for an Australian Centre for International Agricultural Research (ACIAR) project, with two villages located in each of the three provinces. A census survey was conducted by interview with all 238 farmers participating in the ACIAR project, using a structured questionnaire. The interviews were conducted in Lao language and took 1-2 h per farmer. The answers were recorded in Lao and the survey data were translated into English and transcribed into Microsoft Excel, and a linear mixed model in the Genstat statistical analysis package was used to compare quantitative traits between the target provinces. The results showed that the prediction mean of farmer knowledge scores on parasitic disorders, infectious disease, reproduction and nutrition management were significantly different between the target provinces. The prediction mean of farmer knowledge scores on infectious disease questions ranged between 5.11 in HP to 8.54 in XK of 24 marks (P < 0.001). The prediction mean of total knowledge scores was 13.48 in LPB and 19.29 in XK of 42 marks (P < 0.001). The results indicate both the need for and scope required to attain improvements in farmer knowledge of large ruminant health and production. It was concluded that a participatory research and extension programme to address village-level biosecurity and reduce disease risks, plus enhance large ruminant production capabilities of smallholder producers, is a valid and potentially important strategy to address transboundary disease risk and rural poverty in northern Laos. PMID- 21029400 TI - Development of a foot-and-mouth disease infection model in severe combined immunodeficient mice for the preliminary evaluation of antiviral drugs. AB - Recent European guidelines facilitate the use of emergency vaccines during outbreaks of foot-and-mouth disease. Antiviral drugs could be used as a complementary measure. This study aimed at developing a small animal model to assess the in vivo activity of early antiviral lead molecules with anti-foot-and mouth disease virus (FMDV) activity in vitro. In a first attempt, several FMDV strains were titrated in Balb/c mice. Inoculations with O1 Manisa or C1 Noville did not induce clinical disease, whereas Asia1 Shamir induced death too rapidly [i.e. within 4 days post-inoculation (dpi)]. Therefore, we switched to severe combined immunodeficient mice which are frequently used as a model for viral infections and experimental therapeutics. Strain O1 Manisa did not induce clinical disease, but titrations with A22 Iraq, C1 Noville or Asia1 Shamir resulted in virus-induced morbidity (including respiratory problems and weight loss) with subsequent mortality. Inoculations with strain A22 Iraq resulted in a reproducible mean time of death of 6 dpi (this was shorter for the other strains). In this newly developed rodent model, strain A22 Iraq seems the most suited to assess the in vivo anti-FMDV activity of selective inhibitors of FMDV. PMID- 21029401 TI - Rethinking the 'global' in global health: a dialectic approach. AB - BACKGROUND: Current definitions of 'global health' lack specificity about the term 'global'. This debate presents and discusses existing definitions of 'global health' and a common problem inherent therein. It aims to provide a way forward towards an understanding of 'global health' while avoiding redundancy. The attention is concentrated on the dialectics of different concepts of 'global' in their application to malnutrition; HIV, tuberculosis & malaria; and maternal mortality. Further attention is payed to normative objectives attached to 'global health' definitions and to paradoxes involved in attempts to define the field. DISCUSSION: The manuscript identifies denotations of 'global' as 'worldwide', as 'transcending national boundaries' and as 'holistic'. A fourth concept of 'global' as 'supraterritorial' is presented and defined as 'links between the social determinants of health anywhere in the world'. The rhetorical power of the denotations impacts considerably on the object of 'global health', exemplified in the context of malnutrition; HIV, tuberculosis & malaria; and maternal mortality. The 'global' as 'worldwide', as 'transcending national boundaries' and as 'holistic' house contradictions which can be overcome by the fourth concept of 'global' as 'supraterritorial'. The 'global-local-relationship' inherent in the proposed concept coheres with influential anthropological and sociological views despite the use of different terminology. At the same time, it may be assembled with other views on 'global' or amend apparently conflicting ones. The author argues for detaching normative objectives from 'global health' definitions to avoid so called 'entanglement-problems'. Instead, it is argued that the proposed concept constitutes an un-euphemistical approach to describe the inherently politicised field of 'global health'. SUMMARY: While global-as-worldwide and global-as-transcending-national-boundaries are misleading and produce redundancy with public and international health, global-as-supraterritorial provides 'new' objects for research, education and practice while avoiding redundancy. Linked with 'health' as a human right, this concept preserves the rhetorical power of the term 'global health' for more innovative forms of study, research and practice. The dialectic approach reveals that the contradictions involved in the different notions of the term 'global' are only of apparent nature and not exclusive, but have to be seen as complementary to each other if expected to be useful in the final step. PMID- 21029402 TI - Systems-level comparison of host responses induced by pandemic and seasonal influenza A H1N1 viruses in primary human type I-like alveolar epithelial cells in vitro. AB - BACKGROUND: Pandemic influenza H1N1 (pdmH1N1) virus causes mild disease in humans but occasionally leads to severe complications and even death, especially in those who are pregnant or have underlying disease. Cytokine responses induced by pdmH1N1 viruses in vitro are comparable to other seasonal influenza viruses suggesting the cytokine dysregulation as seen in H5N1 infection is not a feature of the pdmH1N1 virus. However a comprehensive gene expression profile of pdmH1N1 in relevant primary human cells in vitro has not been reported. Type I alveolar epithelial cells are a key target cell in pdmH1N1 pneumonia. METHODS: We carried out a comprehensive gene expression profiling using the Affymetrix microarray platform to compare the transcriptomes of primary human alveolar type I-like alveolar epithelial cells infected with pdmH1N1 or seasonal H1N1 virus. RESULTS: Overall, we found that most of the genes that induced by the pdmH1N1 were similarly regulated in response to seasonal H1N1 infection with respect to both trend and extent of gene expression. These commonly responsive genes were largely related to the interferon (IFN) response. Expression of the type III IFN IL29 was more prominent than the type I IFN IFNbeta and a similar pattern of expression of both IFN genes was seen in pdmH1N1 and seasonal H1N1 infection. Genes that were significantly down-regulated in response to seasonal H1N1 but not in response to pdmH1N1 included the zinc finger proteins and small nucleolar RNAs. Gene Ontology (GO) and pathway over-representation analysis suggested that these genes were associated with DNA binding and transcription/translation related functions. CONCLUSIONS: Both seasonal H1N1 and pdmH1N1 trigger similar host responses including IFN-based antiviral responses and cytokine responses. Unlike the avian H5N1 virus, pdmH1N1 virus does not have an intrinsic capacity for cytokine dysregulation. The differences between pdmH1N1 and seasonal H1N1 viruses lay in the ability of seasonal H1N1 virus to down regulate zinc finger proteins and small nucleolar RNAs, which are possible viral transcriptional suppressors and eukaryotic translation initiation factors respectively. These differences may be biologically relevant and may represent better adaptation of seasonal H1N1 influenza virus to the host. PMID- 21029403 TI - The adaptive value of phenotypic plasticity in two ecotypes of a marine gastropod. AB - BACKGROUND: Few surveys have concentrated on studying the adaptive value of phenotypic plasticity within genetically-distinct conspecific ecotypes. Here, we conduct a test to assess the adaptive value that partial phenotypic plasticity may have for survival in the marine gastropod Littorina saxatilis. This species has evolved canalized ecotypes but, nevertheless, the ecotypes show some phenotypic plasticity for the traits under divergent selection between wave exposed and high-predation habitats. RESULTS: We exposed juveniles of each ecotype to several environmental treatments under laboratory conditions in order to produce shape variation associated with plasticity. The two ecotypes from different treatments were then transplanted to the wave-exposed habitat and the survival rate was monitored. Ecotype explained the largest distinction in survival rate while treatment caused variation in survival rate within the ecotype released into its parental habitat which was correlated with plastic changes in shell shape. Snails that had experienced a treatment mimicking the environment of the transplantation location survived with the highest rate, while individuals from the contrary experimental treatment had lower survivorship. CONCLUSIONS: We conclude that the partial plastic response shown in Littorina saxatilis has a significant impact on fitness, although this remains small compared to the overall adaptive difference between ecotypes. PMID- 21029405 TI - Barriers and facilitators of adherence to TB treatment in patients on concomitant TB and HIV treatment: a qualitative study. AB - BACKGROUND: Tuberculosis is a major public health problem in Ethiopia, and a high number of TB patients are co-infected with HIV. There is a need for more knowledge about factors influencing treatment adherence in co-infected patients on concomitant treatment. The aim of the present study is to explore patients' and health care professionals' views about barriers and facilitators to TB treatment adherence in TB/HIV co-infected patients on concomitant treatment for TB and HIV. METHODS: Qualitative study using in-depth interviews with 15 TB/HIV co-infected patients and 9 health professionals and focus group discussions with 14 co-infected patients. RESULTS: We found that interplay of factors is involved in the decision making about medication intake. Factors that influenced adherence to TB treatment positively were beliefs in the curability of TB, beliefs in the severity of TB in the presence of HIV infection and support from families and health professionals. Barriers to treatment adherence were experiencing side effects, pill burden, economic constraints, lack of food, stigma with lack of disclosure, and lack of adequate communication with health professionals. CONCLUSION: Health professionals and policy makers should be aware of factors influencing TB treatment in TB/HIV co-infected patients on concomitant treatment for TB and HIV. Our results suggest that provision of food and minimal financial support might facilitate adherence. Counseling might also facilitate adherence, in particular for those who start ART in the early phases of TB treatment, and beliefs related to side-effects and pill burden should be addressed. Information to the public may reduce TB and HIV related stigma. PMID- 21029406 TI - Manual versus mechanical cardiopulmonary resuscitation. An experimental study in pigs. AB - BACKGROUND: Optimal manual closed chest compressions are difficult to give. A mechanical compression/decompression device, named LUCAS, is programmed to give compression according to the latest international guidelines (2005) for cardiopulmonary resuscitation (CPR). The aim of the present study was to compare manual CPR with LUCAS-CPR. METHODS: 30 kg pigs were anesthetized and intubated. After a base-line period and five minutes of ventricular fibrillation, manual CPR (n = 8) or LUCAS-CPR (n = 8) was started and run for 20 minutes. Professional paramedics gave manual chest compression's alternating in 2-minute periods. Ventilation, one breath for each 10 compressions, was given to all animals. Defibrillation and, if needed, adrenaline were given to obtain a return of spontaneous circulation (ROSC). RESULTS: The mean coronary perfusion pressure was significantly (p < 0.01) higher in the mechanical group, around 20 mmHg, compared to around 5 mmHg in the manual group. In the manual group 54 rib fractures occurred compared to 33 in the LUCAS group (p < 0.01). In the manual group one severe liver injury and one pressure pneumothorax were also seen. All 8 pigs in the mechanical group achieved ROSC, as compared with 3 pigs in the manual group. CONCLUSIONS: LUCAS-CPR gave significantly higher coronary perfusion pressure and significantly fewer rib fractures than manual CPR in this porcine model. PMID- 21029407 TI - Paradoxical embolism following thromboaspiration of an arteriovenous fistula thrombosis: a case report. AB - INTRODUCTION: Paradoxical embolism is an increasingly reported cause of arterial embolism. Several embolic sources have been described, but thrombosis of an arteriovenous fistula as a paradoxical emboligenic source has not, to the best of our knowledge, been reported. CASE PRESENTATION: A 50-year-old Caucasian woman received a renal graft for primary hyperoxaluria. After transplantation, she was maintained on daily hemodialysis. Thrombosis of her arteriovenous fistula occurred two weeks post-transplantation and was treated by thromboaspiration, which was partially successful. During a hemodialysis session immediately following thromboaspiration, she developed a coma with tetraplegia requiring intensive cardiorespiratory resuscitation. Brain magnetic resonance imaging revealed various hyperdense areas in the vertebrobasilar territory resulting from bilateral occlusion of posterior cerebral arteries. Transesophageal echocardiographic examination showed a patent foramen ovale, while pulse echography of the arteriovenous fistula revealed the persistence of extensive clots that were probably the embolic source. A paradoxical embolus through a patent foramen ovale was suggested because of the proximity of the neurological event to the thrombectomy procedure. CONCLUSIONS: The risk of paradoxical embolism in a hemodialyzed patient with a patent foramen ovale deserves consideration and requires careful evaluation in situations of arteriovenous fistula thrombosis. PMID- 21029408 TI - Diffuse small bowel thickening in AIDS patient--a case report. AB - BACKGROUND: Diarrhea is common in HIV/AIDS patients, caused by both classic enteric pathogens and different opportunistic agents. Infection with these different pathogens may lead to similar radiological findings, thus causing diagnostic confusion. CASE PRESENTATION: A 30-yr-old female with AIDS presented with chronic diarrhea of 4 months duration. She had diffuse small bowel thickening present on CT scan of her abdomen, with stool examination showing no parasites. She was erroneously diagnosed as abdominal tuberculosis and given antituberculosis drugs with which she showed no improvement. Repeat stool examination later at a specialized laboratory revealed Cryptosporidium parvum infection.The patient was given an extended course of nitazoxanide treatment, as her stool examination was positive for Cryptosporidium parvum even after 2 weeks of drug consumption. Parasite clearance was documented after 10 weeks of treatment. Interestingly, the bowel thickening reversed with parasitological clearance. CONCLUSIONS: Cryptosporidium parvum may lead to small bowel thickening in AIDS patients. This small bowel thickening may reverse following parasitological clearance. PMID- 21029409 TI - Functional diversity in the color vision of cichlid fishes. AB - BACKGROUND: Color vision plays a critical role in visual behavior. An animal's capacity for color vision rests on the presence of differentially sensitive cone photoreceptors. Spectral sensitivity is a measure of the visual responsiveness of these cones at different light wavelengths. Four classes of cone pigments have been identified in vertebrates, but in teleost fishes, opsin genes have undergone gene duplication events and thus can produce a larger number of spectrally distinct cone pigments. In this study, we examine the question of large-scale variation in color vision with respect to individual, sex and species that may result from differential expression of cone pigments. Cichlid fishes are an excellent model system for examining variation in spectral sensitivity because they have seven distinct cone opsin genes that are differentially expressed. RESULTS: To examine the variation in the number of cones that participate in cichlid spectral sensitivity, we used whole organism electrophysiology, opsin gene expression and empirical modeling. Examination of over 100 spectral sensitivity curves from 34 individuals of three species revealed that (1) spectral sensitivity of individual cichlids was based on different subsets of four or five cone pigments, (2) spectral sensitivity was shaped by multiple cone interactions and (3) spectral sensitivity differed between species and correlated with foraging mode and the spectral reflectance of conspecifics. Our data also suggest that there may be significant differences in opsin gene expression between the sexes. CONCLUSIONS: Our study describes complex opponent and nonopponent cone interactions that represent the requisite neural processing for color vision. We present the first comprehensive evidence for pentachromatic color vision in vertebrates, which offers the potential for extraordinary spectral discrimination capabilities. We show that opsin gene expression in cichlids, and possibly also spectral sensitivity, may be sex-dependent. We argue that females and males sample their visual environment differently, providing a neural basis for sexually dimorphic visual behaviour. The diversification of spectral sensitivity likely contributes to sensory adaptations that enhance the contrast of transparent prey and the detection of optical signals from conspecifics, suggesting a role for both natural and sexual selection in tuning color vision. PMID- 21029410 TI - Quantifying uncertainty, variability and likelihood for ordinary differential equation models. AB - BACKGROUND: In many applications, ordinary differential equation (ODE) models are subject to uncertainty or variability in initial conditions and parameters. Both, uncertainty and variability can be quantified in terms of a probability density function on the state and parameter space. RESULTS: The partial differential equation that describes the evolution of this probability density function has a form that is particularly amenable to application of the well-known method of characteristics. The value of the density at some point in time is directly accessible by the solution of the original ODE extended by a single extra dimension (for the value of the density). This leads to simple methods for studying uncertainty, variability and likelihood, with significant advantages over more traditional Monte Carlo and related approaches especially when studying regions with low probability. CONCLUSIONS: While such approaches based on the method of characteristics are common practice in other disciplines, their advantages for the study of biological systems have so far remained unrecognized. Several examples illustrate performance and accuracy of the approach and its limitations. PMID- 21029411 TI - Modified Gompertz equation for electrotherapy murine tumor growth kinetics: predictions and new hypotheses. AB - BACKGROUND: Electrotherapy effectiveness at different doses has been demonstrated in preclinical and clinical studies; however, several aspects that occur in the tumor growth kinetics before and after treatment have not yet been revealed. Mathematical modeling is a useful instrument that can reveal some of these aspects. The aim of this paper is to describe the complete growth kinetics of unperturbed and perturbed tumors through use of the modified Gompertz equation in order to generate useful insight into the mechanisms that underpin this devastating disease. METHODS: The complete tumor growth kinetics for control and treated groups are obtained by interpolation and extrapolation methods with different time steps, using experimental data of fibrosarcoma Sa-37. In the modified Gompertz equation, a delay time is introduced to describe the tumor's natural history before treatment. Different graphical strategies are used in order to reveal new information in the complete kinetics of this tumor type. RESULTS: The first stage of complete tumor growth kinetics is highly non linear. The model, at this stage, shows different aspects that agree with those reported theoretically and experimentally. Tumor reversibility and the proportionality between regions before and after electrotherapy are demonstrated. In tumors that reach partial remission, two antagonistic post-treatment processes are induced, whereas in complete remission, two unknown antitumor mechanisms are induced. CONCLUSION: The modified Gompertz equation is likely to lead to insights within cancer research. Such insights hold promise for increasing our understanding of tumors as self-organizing systems and, the possible existence of phase transitions in tumor growth kinetics, which, in turn, may have significant impacts both on cancer research and on clinical practice. PMID- 21029412 TI - Creation of a novel peptide with enhanced nuclear localization in prostate and pancreatic cancer cell lines. AB - BACKGROUND: For improved uptake of oligonucleotide-based therapy, the oligonucleotides often are coupled to peptides that facilitate entry into cells. To this end, novel cell-penetrating peptides (CPPs) were designed for mediating intracellular uptake of oligonucleotide-based therapeutics. The novel peptides were based on taking advantage of the nuclear localization properties of transcription factors in combination with a peptide that would bind putatively to cell surfaces. It was observed that adding a glutamate peptide to the N-terminus of the nuclear localization signal (NLS) of the Oct6 transcription factor resulted in a novel CPP with better uptake and better nuclear colocalization than any other peptide tested. RESULTS: Uptake of the novel peptide Glu-Oct6 by cancer cell lines was rapid (in less than 1 hr, more than 60% of DU-145 cells were positive for FITC), complete (by 4 hr, 99% of cells were positive for FITC), concentration-dependent, temperature-dependent, and inhibited by sodium azide (NaN3). Substitution of Phe, Tyr, or Asn moieties for the glutamate portion of the novel peptide resulted in abrogation of novel CPP uptake; however none of the substituted peptides inhibited uptake of the novel CPP when coincubated with cells. Live-cell imaging and analysis by imaging flow cytometry revealed that the novel CPP accumulated in nuclei. Finally, the novel CPP was coupled to a carboxyfluorescein-labeled synthetic oligonucleotide, to see if the peptide could ferry a therapeutic payload into cells. CONCLUSIONS: These studies document the creation of a novel CPP consisting of a glutamate peptide coupled to the N terminus of the Oct6 NLS; the novel CPP exhibited nuclear colocalization as well as uptake by prostate and pancreatic cancer cell lines. PMID- 21029413 TI - Therapy with un-engineered naive rat umbilical cord matrix stem cells markedly inhibits growth of murine lung adenocarcinoma. AB - BACKGROUND: Lung cancer remains the leading cause of cancer-related mortality despite continuous efforts to find effective treatments. Data from the American Cancer Society indicate that while the overall incidence of lung cancer is declining, it continues to rise in women. Stem cell-based therapy has been an emerging strategy to treat various diseases. The purpose of this paper is to determine the efficacy of an intrinsic anti-cancer effect of rat umbilical cord matrix stem cells (UCMSCs) on lung cancer. METHODS: A mouse syngeneic lung carcinoma model was used to test the basic ability of UCMSCs to control the growth of lung cancer. Lung tumors were experimentally induced by tail vein administration of Lewis lung carcinoma (LLC) cells derived from the lung of C57BL/6 mouse. Rat UCMSCs were then administered intratracheally five days later or intravenously on days 5 and 7. The tumor burdens were determined by measuring lung weight three weeks after the treatment. RESULTS: Co-culture of rat UCMSCs with LLC significantly attenuated the proliferation of LLC cells as monitored by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), a tetrazole cell proliferation assay, thymidine uptake, and direct cell counts. In vitro colony assays with rat UCMSCs as feeder layers markedly reduced LLC colony size and number. Co-culture of rat UCMSCs with LLCs causes G0/G1 arrest of cancer cells. This is evident in the decrease of cyclin A and CDK2 expression. The in vivo studies showed that rat UCMSC treatment significantly decreased tumor weight and the total tumor mass. Histological study revealed that intratracheally or systemically administered rat UCMSCs homed to tumor areas and survived for at least 3 weeks without any evidence of differentiation or adverse effects. CONCLUSIONS: These results indicate that rat UCMSCs alone remarkably attenuate the growth of lung carcinoma cells in vitro and in a mouse syngeneic lung carcinoma graft model and could be used for targeted cytotherapy for lung cancer. PMID- 21029414 TI - Cell-free miRNAs may indicate diagnosis and docetaxel sensitivity of tumor cells in malignant effusions. AB - BACKGROUND: Circulating cell-free microRNAs have been identified as potential cancer biomarkers. However, the existence and the potential application of cell free miRNAs in effusion samples are still uncertain. In order to explore the potential role of cell-free miRNA in malignant effusions, we selected 22 miRNAs differentially expressed in the serum of lung cancer patients and studied their expression levels in body cavity effusion samples. METHODS: We measured the expression of 22 miRNAs using qRT-PCR in two samples, which were pooled with 18 malignant and 12 benign effusions, respectively. After discarding 9 lowly expressed miRNAs, a panel of 13 miRNAs were measured in 29 samples (benign n = 11, malignant n = 18). We also carried out a WST-8 test to evaluate the docetaxel sensitivity of tumor cells directly isolated from 15 malignant effusions. RESULTS: We compared the miRNA expression levels between benign and malignant effusions using a Mann-Whitney U test and found miR-24, miR-26a and miR-30d were expressed differently between the two groups (P = 0.006, 0.021 and 0.011, respectively). Cells isolated from effusions rich in cell-free miR-152 were more sensitive to docetaxel (r = 0.60, P = 0.016). CONCLUSIONS: Collectively, our study demonstrated that cell-free miRNAs in the supernatant of effusions may aid in the diagnosis of malignancy and predict chemosensitivity to docetaxel. PMID- 21029415 TI - Anti-oxidative effects of the biennial flower of Panax notoginseng against H2O2 induced cytotoxicity in cultured PC12 cells. AB - BACKGROUND: Radix notoginseng is used in Chinese medicine to improve blood circulation and clotting; however, the pharmacological activities of other parts of Panax notoginseng have yet to be explored. The present study reports the anti oxidative effects of various parts of Panax notoginseng. METHODS: Various parts of Panax notoginseng, including the biennial flower, stem-leaf, root-rhizome, fiber root and sideslip, were used to prepare extracts and analyzed for their anti-oxidation effects, namely suppressing xanthine oxidase activity, H2O2 induced cytotoxicity and H2O2-induced ROS formation. RESULTS: Among various parts of the herb (biennial flower, stem-leaf, root-rhizome, fiber root and sideslip), the water extract of the biennial flower showed the strongest effects in (i) inhibiting the enzymatic activity of xanthine oxidase and (ii) protecting neuronal PC12 cells against H2O2-induced cytotoxicity. Only the water extracts demonstrated such anti-oxidative effects while the ethanol extracts did not exert significant effects in suppressing xanthine oxidase and H2O2-induced neuronal cytotoxicity. CONCLUSIONS: The present study demonstrates the biennial flower of Panax notoginseng to have neuroprotection effect on cultured neurons and the underlying protection mechanism may involve anti-oxidation. PMID- 21029416 TI - Further developments towards a genome-scale metabolic model of yeast. AB - BACKGROUND: To date, several genome-scale network reconstructions have been used to describe the metabolism of the yeast Saccharomyces cerevisiae, each differing in scope and content. The recent community-driven reconstruction, while rigorously evidenced and well annotated, under-represented metabolite transport, lipid metabolism and other pathways, and was not amenable to constraint-based analyses because of lack of pathway connectivity. RESULTS: We have expanded the yeast network reconstruction to incorporate many new reactions from the literature and represented these in a well-annotated and standards-compliant manner. The new reconstruction comprises 1102 unique metabolic reactions involving 924 unique metabolites--significantly larger in scope than any previous reconstruction. The representation of lipid metabolism in particular has improved, with 234 out of 268 enzymes linked to lipid metabolism now present in at least one reaction. Connectivity is emphatically improved, with more than 90% of metabolites now reachable from the growth medium constituents. The present updates allow constraint-based analyses to be performed; viability predictions of single knockouts are comparable to results from in vivo experiments and to those of previous reconstructions. CONCLUSIONS: We report the development of the most complete reconstruction of yeast metabolism to date that is based upon reliable literature evidence and richly annotated according to MIRIAM standards. The reconstruction is available in the Systems Biology Markup Language (SBML) and via a publicly accessible database http://www.comp-sys-bio.org/yeastnet/. PMID- 21029419 TI - MOLA: a bootable, self-configuring system for virtual screening using AutoDock4/Vina on computer clusters. AB - BACKGROUND: Virtual screening of small molecules using molecular docking has become an important tool in drug discovery. However, large scale virtual screening is time demanding and usually requires dedicated computer clusters. There are a number of software tools that perform virtual screening using AutoDock4 but they require access to dedicated Linux computer clusters. Also no software is available for performing virtual screening with Vina using computer clusters. In this paper we present MOLA, an easy-to-use graphical user interface tool that automates parallel virtual screening using AutoDock4 and/or Vina in bootable non-dedicated computer clusters. IMPLEMENTATION: MOLA automates several tasks including: ligand preparation, parallel AutoDock4/Vina jobs distribution and result analysis. When the virtual screening project finishes, an open-office spreadsheet file opens with the ligands ranked by binding energy and distance to the active site. All results files can automatically be recorded on an USB-flash drive or on the hard-disk drive using VirtualBox. MOLA works inside a customized Live CD GNU/Linux operating system, developed by us, that bypass the original operating system installed on the computers used in the cluster. This operating system boots from a CD on the master node and then clusters other computers as slave nodes via ethernet connections. CONCLUSION: MOLA is an ideal virtual screening tool for non-experienced users, with a limited number of multi-platform heterogeneous computers available and no access to dedicated Linux computer clusters. When a virtual screening project finishes, the computers can just be restarted to their original operating system. The originality of MOLA lies on the fact that, any platform-independent computer available can he added to the cluster, without ever using the computer hard-disk drive and without interfering with the installed operating system. With a cluster of 10 processors, and a potential maximum speed-up of 10x, the parallel algorithm of MOLA performed with a speed-up of 8,64* using AutoDock4 and 8,60* using Vina. PMID- 21029418 TI - Determining correspondences between high-frequency MedDRA concepts and SNOMED: a case study. AB - BACKGROUND: The Systematic Nomenclature of Medicine Clinical Terms (SNOMED CT) is being advocated as the foundation for encoding clinical documentation. While the electronic medical record is likely to play a critical role in pharmacovigilance the detection of adverse events due to medications - classification and reporting of Adverse Events is currently based on the Medical Dictionary of Regulatory Activities (MedDRA). Complete and high-quality MedDRA-to-SNOMED CT mappings can therefore facilitate pharmacovigilance. The existing mappings, as determined through the Unified Medical Language System (UMLS), are partial, and record only one-to-one correspondences even though SNOMED CT can be used compositionally. Efforts to map previously unmapped MedDRA concepts would be most productive if focused on concepts that occur frequently in actual adverse event data. We aimed to identify aspects of MedDRA that complicate mapping to SNOMED CT, determine pattern in unmapped high-frequency MedDRA concepts, and to identify types of integration errors in the mapping of MedDRA to UMLS. METHODS: Using one years' data from the US Federal Drug Administrations Adverse Event Reporting System, we identified MedDRA preferred terms that collectively accounted for 95% of both Adverse Events and Therapeutic Indications records. After eliminating those already mapping to SNOMED CT, we attempted to map the remaining 645 Adverse Event and 141 Therapeutic-Indications preferred terms with software assistance. RESULTS: All but 46 Adverse-Event and 7 Therapeutic-Indications preferred terms could be composed using SNOMED CT concepts: none of these required more than 3 SNOMED CT concepts to compose. We describe the common composition patterns in the paper. About 30% of both Adverse-Event and Therapeutic-Indications Preferred Terms corresponded to single SNOMED CT concepts: the correspondence was detectable by human inspection but had been missed during the integration process, which had created duplicated concepts in UMLS. CONCLUSIONS: Identification of composite mapping patterns, and the types of errors that occur in the MedDRA content within UMLS, can focus larger-scale efforts on improving the quality of such mappings, which may assist in the creation of an adverse events ontology. PMID- 21029417 TI - PAR1- and PAR2-induced innate immune markers are negatively regulated by PI3K/Akt signaling pathway in oral keratinocytes. AB - BACKGROUND: Protease-Activated Receptors (PARs), members of G-protein-coupled receptors, are activated by proteolytic activity of various proteases. Activation of PAR1 and PAR2 triggers innate immune responses in human oral keratinocytes (HOKs), but the signaling pathways downstream of PAR activation in HOKs have not been clearly defined. In this study, we aimed to determine if PAR1- and PAR2 mediated signaling differs in the induction of innate immune markers CXCL3, CXCL5 and CCL20 via ERK, p38 and PI3K/Akt. RESULTS: Our data show the induction of innate immunity by PAR1 requires both p38 and ERK MAP kinases, while PAR2 prominently signals via p38. However, inhibition of PI3K enhances expression of innate immune markers predominantly via suppressing p38 phosphorylation signaled by PAR activation. CONCLUSION: Our data indicate that proteases mediating PAR1 and PAR2 activation differentially signal via MAP kinase cascades. In addition, the production of chemokines induced by PAR1 and PAR2 is suppressed by PI3K/Akt, thus keeping the innate immune responses of HOK in balance. The results of our study provide a novel insight into signaling pathways involved in PAR activation. PMID- 21029420 TI - The genetic basis of multiple sclerosis: a model for MS susceptibility. AB - BACKGROUND: MS-pathogenesis is known to involve both multiple environmental events, and several independent genetic risk-factors. METHODS: A model of susceptibility is developed and a mathematical analysis undertaken to elucidate the nature of genetic susceptibility to MS and to understand the constraints that are placed on the genetic basis of MS, both by the known epidemiological facts of this disease and by the known frequency of the HLA DRB1*1501 allele in the general populations of northern Europe and North America. RESULTS: For the large majority of cases (possibly all), MS develops, in part, because an individual is genetically susceptible. Nevertheless, 2.2% or less of the general population is genetically susceptible. Moreover, from the model, the number of susceptibility loci that need to be in a "susceptible allelic state" to produce MS susceptibility is small (11-18), whereas the total number of such susceptibility loci is large (50-200), and their "frequency of susceptibility" is low (i.e., <= 0.12). The optimal solution to the model equations (which occurs when 80% of the loci are recessive) predicts the epidemiological data quite closely. CONCLUSIONS: The model suggests that combinations of only a small number of genetic loci in a "susceptible allelic state" produce MS-susceptibility. Nevertheless, genome-wide associations studies with hundreds of thousands of SNPs, are plagued by both false-positive and false-negative identifications and, consequently, emphasis has been rightly placed on the replicability of findings. Nevertheless, because genome-wide screens don't distinguish between true susceptibility-loci and disease-modifying-loci, and because only true susceptibility-loci are constrained by the model, unraveling the two will not be possible using this approach.The model also suggests that HLA DRB1 may not be as uniquely important for MS susceptibility as currently believed. Thus, this allele is only one among a hundred or more loci involved in MS susceptibility. Even though the "frequency of susceptibility" at the HLA DRB1 locus is four-fold that of other loci, the penetrance of those susceptible genotypes that include this allele is no different from those that don't. Also, almost 50% of genetically-susceptible individuals, lack this allele. Moreover, of those who have it, only a small fraction (<= 5.2%) are even susceptible to getting MS. PMID- 21029421 TI - Cancer-related ectopic expression of the bone-related transcription factor RUNX2 in non-osseous metastatic tumor cells is linked to cell proliferation and motility. AB - INTRODUCTION: Metastatic breast cancer cells frequently and ectopically express the transcription factor RUNX2, which normally attenuates proliferation and promotes maturation of osteoblasts. RUNX2 expression is inversely regulated with respect to cell growth in osteoblasts and deregulated in osteosarcoma cells. METHODS: Here, we addressed whether the functional relationship between cell growth and RUNX2 gene expression is maintained in breast cancer cells. We also investigated whether the aberrant expression of RUNX2 is linked to phenotypic parameters that could provide a selective advantage to cells during breast cancer progression. RESULTS: We find that, similar to its regulation in osteoblasts, RUNX2 expression in MDA-MB-231 breast adenocarcinoma cells is enhanced upon growth factor deprivation, as well as upon deactivation of the mitogen-dependent MEK-Erk pathway or EGFR signaling. Reduction of RUNX2 levels by RNAi has only marginal effects on cell growth and expression of proliferation markers in MDA-MB 231 breast cancer cells. Thus, RUNX2 is not a critical regulator of cell proliferation in this cell type. However, siRNA depletion of RUNX2 in MDA-MB-231 cells reduces cell motility, while forced exogenous expression of RUNX2 in MCF7 cells increases cell motility. CONCLUSIONS: Our results support the emerging concept that the osteogenic transcription factor RUNX2 functions as a metastasis related oncoprotein in non-osseous cancer cells. PMID- 21029422 TI - Esophageal perforation in South of Sweden: results of surgical treatment in 125 consecutive patients. AB - BACKGROUND: For many years there has been a debate as to which is the method of choice in treating patients with esophageal perforation. The literature consists mainly of small case series. Strategies for aiding patients struck with this disease is changing as new and less traumatic treatment options are developing. We studied a relatively large consecutive material of esophageal perforations in an effort to evaluate prognostic factors, diagnostic efforts and treatment strategy in these patients. METHODS: 125 consecutive patients treated at the University Hospital of Lund from 1970 to 2006 were studied retrospectively. Prognostic factors were evaluated using the Cox proportional hazards model. RESULTS: Pre-operative ASA score was the only factor that significantly influenced outcome. Neck incision for cervical perforation (n = 8) and treatment with a covered stent with or without open drainage for a thoracic perforation (n = 6) had the lowest mortality. Esophageal resection (n = 8) had the highest mortality. A CAT scan or an oesophageal X-ray with oral contrast were the most efficient diagnostic tools. The preferred treatment strategy changed over the course of the study period, from a more aggressive surgical approach towards using covered stents to seal the perforation. CONCLUSION: Pre-operative ASA score was the only factor that significantly influenced outcome in this study. Treatment strategies are changing as less traumatic options have become available. Sealing an esophageal perforation with a covered stent, in combination with open or closed drainage when necessary, is a promising treatment strategy. PMID- 21029423 TI - Genetic variants in mannose receptor gene (MRC1) confer susceptibility to increased risk of sarcoidosis. AB - BACKGROUND: Mannose receptor (MR) is a member of the C-type lectin receptor family involved in pathogen molecular-pattern recognition and thought to be critical in shaping host immune response. The aim of this study was to investigate potential associations of genetic variants in the MRC1 gene with sarcoidosis. METHODS: Nine single nucleotide polymorphisms (SNPs), encompassing the MRC1 gene, were genotyped in a total of 605 Japanese consisting of 181 sarcoidosis patients and 424 healthy controls. RESULTS: Suggestive evidence of association between rs691005 SNP and risk of sarcoidosis was observed independent of sex and age in a recessive model (P = 0.001). CONCLUSIONS: These results suggest that MRC1 is an important candidate gene for sarcoidosis. This is the first study to imply that genetic variants in MRC1, a major member of the C-type lectin, contribute to the development of sarcoidosis. PMID- 21029424 TI - Declining incidence of imported malaria in the Netherlands, 2000-2007. AB - BACKGROUND: To describe the epidemiology and trends of imported malaria in the Netherlands from 2000 through 2007. METHODS: Based on national surveillance data regarding all reported infections of imported malaria, diagnosed 2000 through 2007, incidence and trends of imported malaria in the Netherlands were estimated. Travellers statistics were used to estimate incidence, and data on malaria chemoprophylaxis prescriptions were used to estimate the number of unprotected travellers. RESULTS: Importation of malaria to the Netherlands is declining even as more travellers visit malaria-endemic countries. On average, 82% were acquired in sub-Saharan Africa, and 75% were caused by Plasmodium falciparum. The overall incidence in imported falciparum malaria fell from 21.5 to 6.6/10,000 of unprotected travellers. The percentage of unprotected travellers rose from 47% to 52% of all travellers. The incidence of imported falciparum infections is greatest from Middle and West Africa, and decreased from 121.3 to 36.5/10,000 travellers. The import of malaria from this region by immigrants visiting friends and relatives (VFR) decreased from 138 infections in 2000, to 69 infections in 2007. CONCLUSION: The annual number of imported malaria shows a continuing declining trend, even with an increasing number of travellers visiting malaria endemic countries. VFR import less malaria than previously, and contribute largely to the declining incidence seen. The decline is not readily explained by increased use of chemoprophylaxis and may reflect a reduced risk of infection due to decreasing local malaria transmission as observed in some malaria endemic areas. Nevertheless, the increasing number of unprotected travellers remains worrisome. PMID- 21029425 TI - The beneficial effects of exercise in rodents are preserved after detraining: a phenomenon unrelated to GLUT4 expression. AB - BACKGROUND: Although exercise training has well-known cardiorespiratory and metabolic benefits, low compliance with exercise training programs is a fact, and the harmful effects of physical detraining regarding these adaptations usually go unnoticed. We investigated the effects of exercise detraining on blood pressure, insulin sensitivity, and GLUT4 expression in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY). METHODS: Studied animals were randomized into sedentary, trained (treadmill running/5 days a week, 60 min/day for 10 weeks), 1 week of detraining, and 2 weeks of detraining. Blood pressure (tail-cuff system), insulin sensitivity (kITT), and GLUT4 (Western blot) in heart, gastrocnemius and white fat tissue were measured. RESULTS: Exercise training reduced blood pressure (19%), improved insulin sensitivity (24%), and increased GLUT4 in the heart (+34%); gastrocnemius (+36%) and fat (+22%) in SHR. In WKY no change in either blood pressure or insulin sensitivity were observed, but there was an increase in GLUT4 in the heart (+25%), gastrocnemius (+45%) and fat (+36%) induced by training. Both periods of detraining did not induce any change in neither blood pressure nor insulin sensitivity in SHR and WKY. One-week detraining reduced GLUT4 in SHR (heart: -28%; fat: -23%) and WKY (heart: -19%; fat: -22%); GLUT4 in the gastrocnemius was reduced after a 2-week detraining (SHR: -35%; WKY: -25%). There was a positive correlation between GLUT4 (gastrocnemius) and the maximal velocity in the exercise test (r = 0.60, p = 0.004). CONCLUSIONS: The study findings show that in detraining, despite reversion of the enhanced GLUT4 expression, cardiorespiratory and metabolic beneficial effects of exercise are preserved. PMID- 21029426 TI - Risk factor analysis and spatiotemporal CART model of cryptosporidiosis in Queensland, Australia. AB - BACKGROUND: It remains unclear whether it is possible to develop a spatiotemporal epidemic prediction model for cryptosporidiosis disease. This paper examined the impact of social economic and weather factors on cryptosporidiosis and explored the possibility of developing such a model using social economic and weather data in Queensland, Australia. METHODS: Data on weather variables, notified cryptosporidiosis cases and social economic factors in Queensland were supplied by the Australian Bureau of Meteorology, Queensland Department of Health, and Australian Bureau of Statistics, respectively. Three-stage spatiotemporal classification and regression tree (CART) models were developed to examine the association between social economic and weather factors and monthly incidence of cryptosporidiosis in Queensland, Australia. The spatiotemporal CART model was used for predicting the outbreak of cryptosporidiosis in Queensland, Australia. RESULTS: The results of the classification tree model (with incidence rates defined as binary presence/absence) showed that there was an 87% chance of an occurrence of cryptosporidiosis in a local government area (LGA) if the socio economic index for the area (SEIFA) exceeded 1021, while the results of regression tree model (based on non-zero incidence rates) show when SEIFA was between 892 and 945, and temperature exceeded 32 degrees C, the relative risk (RR) of cryptosporidiosis was 3.9 (mean morbidity: 390.6/100,000, standard deviation (SD): 310.5), compared to monthly average incidence of cryptosporidiosis. When SEIFA was less than 892 the RR of cryptosporidiosis was 4.3 (mean morbidity: 426.8/100,000, SD: 319.2). A prediction map for the cryptosporidiosis outbreak was made according to the outputs of spatiotemporal CART models. CONCLUSIONS: The results of this study suggest that spatiotemporal CART models based on social economic and weather variables can be used for predicting the outbreak of cryptosporidiosis in Queensland, Australia. PMID- 21029427 TI - Optimizing structural modeling for a specific protein scaffold: knottins or inhibitor cystine knots. AB - BACKGROUND: Knottins are small, diverse and stable proteins with important drug design potential. They can be classified in 30 families which cover a wide range of sequences (1621 sequenced), three-dimensional structures (155 solved) and functions (> 10). Inter knottin similarity lies mainly between 15% and 40% sequence identity and 1.5 to 4.5 A backbone deviations although they all share a tightly knotted disulfide core. This important variability is likely to arise from the highly diverse loops which connect the successive knotted cysteines. The prediction of structural models for all knottin sequences would open new directions for the analysis of interaction sites and to provide a better understanding of the structural and functional organization of proteins sharing this scaffold. RESULTS: We have designed an automated modeling procedure for predicting the three-dimensionnal structure of knottins. The different steps of the homology modeling pipeline were carefully optimized relatively to a test set of knottins with known structures: template selection and alignment, extraction of structural constraints and model building, model evaluation and refinement. After optimization, the accuracy of predicted models was shown to lie between 1.50 and 1.96 A from native structures at 50% and 10% maximum sequence identity levels, respectively. These average model deviations represent an improvement varying between 0.74 and 1.17 A over a basic homology modeling derived from a unique template. A database of 1621 structural models for all known knottin sequences was generated and is freely accessible from our web server at http://knottin.cbs.cnrs.fr. Models can also be interactively constructed from any knottin sequence using the structure prediction module Knoter1D3D available from our protein analysis toolkit PAT at http://pat.cbs.cnrs.fr. CONCLUSIONS: This work explores different directions for a systematic homology modeling of a diverse family of protein sequences. In particular, we have shown that the accuracy of the models constructed at a low level of sequence identity can be improved by 1) a careful optimization of the modeling procedure, 2) the combination of multiple structural templates and 3) the use of conserved structural features as modeling restraints. PMID- 21029428 TI - Resistin is associated with mortality in patients with traumatic brain injury. AB - INTRODUCTION: Recently, we reported that high levels of resistin are present in the peripheral blood of patients with intracerebral hemorrhage and are associated with a poor outcome. However, not much is known regarding the change in plasma resistin and its relation with mortality after traumatic brain injury (TBI). Thus, we sought to investigate change in plasma resistin level after TBI and to evaluate its relation with disease outcome. METHODS: Fifty healthy controls and 94 patients with acute severe TBI were included. Plasma samples were obtained on admission and at days 1, 2, 3, 5 and 7 after TBI. Its concentration was measured by enzyme-linked immunosorbent assay. RESULTS: Twenty-six patients (27.7%) died from TBI within 1 month. After TBI, plasma resistin level in patients increased during the 6-hour period immediately after TBI, peaked within 24 hours, plateaued at day 2, decreased gradually thereafter and was substantially higher than that in healthy controls during the 7-day period. A forward stepwise logistic regression selected plasma resistin level (odds ratio, 1.107; 95% confidence interval, 1.014-1.208; P = 0.023) as an independent predictor for 1-month mortality of patients. A multivariate linear regression showed that plasma resistin level was negatively associated with Glasgow Coma Scale score (t = 6.567, P < 0.001). A receiver operating characteristic curve identified plasma resistin cutoff level (30.8 ng/mL) that predicted 1-month mortality with the optimal sensitivity (84.6%) and specificity (75.0%) values (area under curve, 0.854; 95% confidence interval, 0.766-0.918; P < 0.001). CONCLUSIONS: Increased plasma resistin level is found and associated with Glasgow Coma Scale score and mortality after TBI. PMID- 21029430 TI - Consistent levels of A-to-I RNA editing across individuals in coding sequences and non-conserved Alu repeats. AB - BACKGROUND: Adenosine to inosine (A-to-I) RNA-editing is an essential post transcriptional mechanism that occurs in numerous sites in the human transcriptome, mainly within Alu repeats. It has been shown to have consistent levels of editing across individuals in a few targets in the human brain and altered in several human pathologies. However, the variability across human individuals of editing levels in other tissues has not been studied so far. RESULTS: Here, we analyzed 32 skin samples, looking at A-to-I editing level in three genes within coding sequences and in the Alu repeats of six different genes. We observed highly consistent editing levels across different individuals as well as across tissues, not only in coding targets but, surprisingly, also in the non evolutionary conserved Alu repeats. CONCLUSIONS: Our findings suggest that A-to-I RNA-editing of Alu elements is a tightly regulated process and, as such, might have been recruited in the course of primate evolution for post transcriptional regulatory mechanisms. PMID- 21029429 TI - Increased renal sodium absorption by inhibition of prostaglandin synthesis during fasting in healthy man. A possible role of the epithelial sodium channels. AB - BACKGROUND: Treatment with prostaglandin inhibitors can reduce renal function and impair renal water and sodium excretion. We tested the hypotheses that a reduction in prostaglandin synthesis by ibuprofen treatment during fasting decreased renal water and sodium excretion by increased absorption of water and sodium via the aquaporin2 water channels and the epithelial sodium channels. METHODS: The effect of ibuprofen, 600 mg thrice daily, was measured during fasting in a randomized, placebo-controlled, double-blinded crossover study of 17 healthy humans. The subjects received a standardized diet on day 1, fasted at day 2, and received an IV infusion of 3% NaCl on day 3. The effect variables were urinary excretions of aquaporin2 (u-AQP2), the beta-fraction of the epithelial sodium channel (u-ENaCbeta), cyclic-AMP (u-cAMP), prostaglandin E2 (u-PGE2). Free water clearance (CH2O), fractional excretion of sodium (FENa), and plasma concentrations of vasopressin, angiotensin II, aldosterone, atrial-, and brain natriuretic peptide. RESULTS: Ibuprofen decreased u-AQP2, u-PGE2, and FENa at all parts of the study. During the same time, ibuprofen significantly increased u ENaCbeta. Ibuprofen did not change the response in p-AVP, u-c-AMP, urinary output, and free water clearance during any of these periods. Atrial-and brain natriuretic peptide were higher. CONCLUSION: During inhibition of prostaglandin synthesis, urinary sodium excretion decreased in parallel with an increase in sodium absorption and increase in u-ENaCbeta. U-AQP2 decreased indicating that water transport via AQP2 fell. The vasopressin-c-AMP-axis did not mediate this effect, but it may be a consequence of the changes in the natriuretic peptide system and/or the angiotensin-aldosterone system TRIAL REGISTRATION: Clinical Trials Identifier: NCT00281762. PMID- 21029431 TI - Cor Triatriatum Sinister diagnosed in adult life with three dimensional transesophageal echocardiography. AB - BACKGROUND: Cor triatriatum is a very rare congenital abnormality, usually symptomatic during childhood, diagnosis in adult age is less common. CASE PRESENTATION: We report the case of a 40 years old woman referred to our hospital for atrial flutter ablation, transthoracic cardiac bidimensional echocardiography showed an abnormal membrane bisecting the left atrium, the diagnosis of cor triatriatum was fully made via three dimensional transesophageal echocardiography. More interestingly three other cardiac anomalies were associated: ostium secundum atrial septal defect, dilated coronary sinus due probably to persistent left superior vena cava and normally functioning bicuspid aortic valve. CONCLUSIONS: Cor triatriatum sinister in adult life is important to recognize because it may be easily surgically correctable when hemodynamically significant. Three Dimensional transesophageal echocardiography is a minimally invasive and highly sensitive diagnostic modality. PMID- 21029432 TI - Transcription of the T4 late genes. AB - This article reviews the current state of understanding of the regulated transcription of the bacteriophage T4 late genes, with a focus on the underlying biochemical mechanisms, which turn out to be unique to the T4-related family of phages or significantly different from other bacterial systems. The activator of T4 late transcription is the gene 45 protein (gp45), the sliding clamp of the T4 replisome. Gp45 becomes topologically linked to DNA through the action of its clamp-loader, but it is not site-specifically DNA-bound, as other transcriptional activators are. Gp45 facilitates RNA polymerase recruitment to late promoters by interacting with two phage-encoded polymerase subunits: gp33, the co-activator of T4 late transcription; and gp55, the T4 late promoter recognition protein. The emphasis of this account is on the sites and mechanisms of actions of these three proteins, and on their roles in the formation of transcription-ready open T4 late promoter complexes. PMID- 21029433 TI - Transcriptional control in the prereplicative phase of T4 development. AB - Control of transcription is crucial for correct gene expression and orderly development. For many years, bacteriophage T4 has provided a simple model system to investigate mechanisms that regulate this process. Development of T4 requires the transcription of early, middle and late RNAs. Because T4 does not encode its own RNA polymerase, it must redirect the polymerase of its host, E. coli, to the correct class of genes at the correct time. T4 accomplishes this through the action of phage-encoded factors. Here I review recent studies investigating the transcription of T4 prereplicative genes, which are expressed as early and middle transcripts. Early RNAs are generated immediately after infection from T4 promoters that contain excellent recognition sequences for host polymerase. Consequently, the early promoters compete extremely well with host promoters for the available polymerase. T4 early promoter activity is further enhanced by the action of the T4 Alt protein, a component of the phage head that is injected into E. coli along with the phage DNA. Alt modifies Arg265 on one of the two alpha subunits of RNA polymerase. Although work with host promoters predicts that this modification should decrease promoter activity, transcription from some T4 early promoters increases when RNA polymerase is modified by Alt. Transcription of T4 middle genes begins about 1 minute after infection and proceeds by two pathways: 1) extension of early transcripts into downstream middle genes and 2) activation of T4 middle promoters through a process called sigma appropriation. In this activation, the T4 co-activator AsiA binds to Region 4 of sigma70, the specificity subunit of RNA polymerase. This binding dramatically remodels this portion of sigma70, which then allows the T4 activator MotA to also interact with sigma70. In addition, AsiA restructuring of sigma70 prevents Region 4 from forming its normal contacts with the -35 region of promoter DNA, which in turn allows MotA to interact with its DNA binding site, a MotA box, centered at the 30 region of middle promoter DNA. T4 sigma appropriation reveals how a specific domain within RNA polymerase can be remolded and then exploited to alter promoter specificity. PMID- 21029434 TI - Mobile DNA elements in T4 and related phages. AB - Mobile genetic elements are common inhabitants of virtually every genome where they can exert profound influences on genome structure and function in addition to promoting their own spread within and between genomes. Phage T4 and related phage have long served as a model system for understanding the molecular mechanisms by which a certain class of mobile DNA, homing endonucleases, promote their spread. Homing endonucleases are site-specific DNA endonucleases that initiate mobility by introducing double-strand breaks at defined positions in genomes lacking the endonuclease gene, stimulating repair and recombination pathways that mobilize the endonuclease coding region. In phage T4, homing endonucleases were first discovered as encoded within the self-splicing td, nrdB and nrdD introns of T4. Genomic data has revealed that homing endonucleases are extremely widespread in T-even-like phage, as evidenced by the astounding fact that ~11% of the T4 genome encodes homing endonuclease genes, with most of them located outside of self-splicing introns. Detailed studies of the mobile td intron and its encoded endonuclease, I-TevI, have laid the foundation for genetic, biochemical and structural aspects that regulate the mobility process, and more recently have provided insights into regulation of homing endonuclease function. Here, we summarize the current state of knowledge regarding T4-encoded homing endonucleases, with particular emphasis on the td/I-TevI model system. We also discuss recent progress in the biology of free-standing endonucleases, and present areas of future research for this fascinating class of mobile genetic elements. PMID- 21029435 TI - T4 genes in the marine ecosystem: studies of the T4-like cyanophages and their role in marine ecology. AB - From genomic sequencing it has become apparent that the marine cyanomyoviruses capable of infecting strains of unicellular cyanobacteria assigned to the genera Synechococcus and Prochlorococcus are not only morphologically similar to T4, but are also genetically related, typically sharing some 40-48 genes. The large majority of these common genes are the same in all marine cyanomyoviruses so far characterized. Given the fundamental physiological differences between marine unicellular cyanobacteria and heterotrophic hosts of T4-like phages it is not surprising that the study of cyanomyoviruses has revealed novel and fascinating facets of the phage-host relationship. One of the most interesting features of the marine cyanomyoviruses is their possession of a number of genes that are clearly of host origin such as those involved in photosynthesis, like the psbA gene that encodes a core component of the photosystem II reaction centre. Other host-derived genes encode enzymes involved in carbon metabolism, phosphate acquisition and ppGpp metabolism. The impact of these host-derived genes on phage fitness has still largely to be assessed and represents one of the most important topics in the study of this group of T4-like phages in the laboratory. However, these phages are also of considerable environmental significance by virtue of their impact on key contributors to oceanic primary production and the true extent and nature of this impact has still to be accurately assessed. PMID- 21029436 TI - Genomes of the T4-related bacteriophages as windows on microbial genome evolution. AB - The T4-related bacteriophages are a group of bacterial viruses that share morphological similarities and genetic homologies with the well-studied Escherichia coli phage T4, but that diverge from T4 and each other by a number of genetically determined characteristics including the bacterial hosts they infect, the sizes of their linear double-stranded (ds) DNA genomes and the predicted compositions of their proteomes. The genomes of about 40 of these phages have been sequenced and annotated over the last several years and are compared here in the context of the factors that have determined their diversity and the diversity of other microbial genomes in evolution. The genomes of the T4 relatives analyzed so far range in size between ~160,000 and ~250,000 base pairs (bp) and are mosaics of one another, consisting of clusters of homology between them that are interspersed with segments that vary considerably in genetic composition between the different phage lineages. Based on the known biological and biochemical properties of phage T4 and the proteins encoded by the T4 genome, the T4 relatives reviewed here are predicted to share a genetic core, or "Core Genome" that determines the structural design of their dsDNA chromosomes, their distinctive morphology and the process of their assembly into infectious agents (phage morphogenesis). The Core Genome appears to be the most ancient genetic component of this phage group and constitutes a mere 12-15% of the total protein encoding potential of the typical T4-related phage genome. The high degree of genetic heterogeneity that exists outside of this shared core suggests that horizontal DNA transfer involving many genetic sources has played a major role in diversification of the T4-related phages and their spread to a wide spectrum of bacterial species domains in evolution. We discuss some of the factors and pathways that might have shaped the evolution of these phages and point out several parallels between their diversity and the diversity generally observed within all groups of interrelated dsDNA microbial genomes in nature. PMID- 21029437 TI - Bacteriophage T4 and its relatives. PMID- 21029439 TI - Comparison of 3T MR scanners in regional cartilage-thickness analysis in osteoarthritis: a cross-sectional multicenter, multivendor study. AB - INTRODUCTION: Cartilage thickness from MR images has been identified as a possible biomarker in knee osteoarthritis (OA) research. The ability to acquire MR data at multiple centers by using different vendors' scanners would facilitate patient recruitment and shorten the duration of OA trials. Several vendors manufacture 3T MR scanners, including Siemens, Philips Medical Systems, and GE Healthcare. This study investigates whether quantitative MR assessments of cartilage morphology are comparable between scanners of three different vendors. METHODS: Twelve subjects with symptoms of knee OA and one or more risk factors had their symptomatic knee scanned on each of the three vendor's scanners located in three sites in the UK: Manchester (Philips), York (GE), and Liverpool (Siemens). The NIH OAI study protocol was used for the Siemens scanner, and equivalent protocols were developed for the Philips and GE scanners with vendors' advice. Cartilage was segmented manually from sagittal 3D images. By using recently described techniques for Anatomically Corresponded Regional Analysis of Cartilage (ACRAC), a statistical model was used anatomically to align all the images and to produce detailed maps of mean differences in cartilage-thickness measures between scanners. Measures of cartilage mean thickness were computed in anatomically equivalent regions for each subject and scanner image. RESULTS: The ranges of mean cartilage-thickness measures for this cohort were similar for all regions and across all scanners. Philips intrascanner root-mean-square coefficients of variation were low in the range from 2.6% to 4.6%. No significant differences were found for thickness measures of the weight-bearing femorotibial regions from the Philips and Siemens images except for the central medial femur compartment (P = 0.04). Compared with the other two scanners, the GE scanner provided consistently lower mean thickness measures in the central femoral regions (mean difference, -0.16 mm) and higher measures in the tibial compartments (mean difference, +0.19 mm). CONCLUSIONS: The OAI knee-imaging protocol, developed on the Siemens platform, can be applied to research and trials by using other vendors' 3T scanners giving comparable morphologic results. Accurate sequence optimization, differences in image postprocessing, and extremity coil type are critical factors for interscanner precision of quantitative analysis of cartilage morphology. It is still recommended that longitudinal observations on individuals should be performed on the same scanner and that assessment of intra- and interscanner precision errors is undertaken before commencement of the main study. PMID- 21029440 TI - Transcriptome bioinformatic analysis identifies potential therapeutic mechanism of pentylenetetrazole in down syndrome. AB - BACKGROUND: Pentylenetetrazole (PTZ) has recently been found to ameliorate cognitive impairment in rodent models of Down syndrome (DS). The mechanism underlying PTZ's therapeutic effect in DS is however not clear. Microarray profiling has previously reported differential expression, both up- and down regulation, of genes in DS. Given this, transcriptomic data related to PTZ treatment, if available, could be used to understand the drug's therapeutic mechanism in DS. No such mammalian data however exists. Nevertheless, a Drosophila model inspired by PTZ induced kindling plasticity in rodents has recently been described. Microarray profiling has shown PTZ's downregulatory effect on gene expression in the fly heads. METHODS: In a comparative transcriptomics approach, I have analyzed the available microarray data in order to identify potential therapeutic mechanism of PTZ in DS. In the analysis, summary data of up- and down-regulated genes reported in human DS studies and of down-regulated genes reported in the Drosophila model has been used. RESULTS: I find that transcriptomic correlate of chronic PTZ in Drosophila counteracts that of DS. Genes downregulated by PTZ significantly over-represent genes upregulated in DS and under-represent genes downregulated in DS. Further, the genes which are common in the downregulated and upregulated DS set show enrichment for MAP kinase pathway. CONCLUSION: My analysis suggests that downregulation of MAP kinase pathway may mediate therapeutic effect of PTZ in DS. Existing evidence implicating MAP kinase pathway in DS supports this observation. PMID- 21029438 TI - Whole genome wide expression profiles of Vitis amurensis grape responding to downy mildew by using Solexa sequencing technology. AB - BACKGROUND: Downy mildew (DM), caused by pathogen Plasmopara viticola (PV) is the single most damaging disease of grapes (Vitis L.) worldwide. However, the mechanisms of the disease development in grapes are poorly understood. A method for estimating gene expression levels using Solexa sequencing of Type I restriction-endonuclease-generated cDNA fragments was used for deep sequencing the transcriptomes resulting from PV infected leaves of Vitis amurensis Rupr. cv. Zuoshan-1. Our goal is to identify genes that are involved in resistance to grape DM disease. RESULTS: Approximately 8.5 million (M) 21-nt cDNA tags were sequenced in the cDNA library derived from PV pathogen-infected leaves, and about 7.5 M were sequenced from the cDNA library constructed from the control leaves. When annotated, a total of 15,249 putative genes were identified from the Solexa sequencing tags for the infection (INF) library and 14,549 for the control (CON) library. Comparative analysis between these two cDNA libraries showed about 0.9% of the unique tags increased by at least five-fold, and about 0.6% of the unique tags decreased more than five-fold in infected leaves, while 98.5% of the unique tags showed less than five-fold difference between the two samples. The expression levels of 12 differentially expressed genes were confirmed by Real time RT-PCR and the trends observed agreed well with the Solexa expression profiles, although the degree of change was lower in amplitude. After pathway enrichment analysis, a set of significantly enriched pathways were identified for the differentially expressed genes (DEGs), which associated with ribosome structure, photosynthesis, amino acid and sugar metabolism. CONCLUSIONS: This study presented a series of candidate genes and pathways that may contribute to DM resistance in grapes, and illustrated that the Solexa-based tag-sequencing approach was a powerful tool for gene expression comparison between control and treated samples. PMID- 21029441 TI - MicroR159 regulation of most conserved targets in Arabidopsis has negligible phenotypic effects. AB - BACKGROUND: A current challenge of microRNA (miRNA) research is the identification of biologically relevant miRNA:target gene relationships. In plants, high miRNA:target gene complementarity has enabled accurate target predictions, and slicing of target mRNAs has facilitated target validation through rapid amplification of 5' cDNA ends (5'-RACE) analysis. Together, these approaches have identified more than 20 targets potentially regulated by the deeply conserved miR159 family in Arabidopsis, including eight MYB genes with highly conserved miR159 target sites. However, genetic analysis has revealed the functional specificity of the major family members, miR159a and miR159b is limited to only two targets, MYB33 and MYB65. Here, we examine the functional role of miR159 regulation for the other potential MYB target genes. RESULTS: For these target genes, functional analysis failed to identify miR159 regulation that resulted in any major phenotypic impact, either at the morphological or molecular level. This appears to be mainly due to the quiescent nature of the remaining family member, MIR159c. Although its expression overlaps in a temporal and spatial cell-specific manner with a subset of these targets in anthers, the abundance of miR159c is extremely low and concomitantly a mir159c mutant displays no anther defects. Examination of potential miR159c targets with conserved miR159 binding sites found neither their spatial or temporal expression domains appeared miR159 regulated, despite the detection of miR159-guided cleavage products by 5' RACE. Moreover, expression of a miR159-resistant target (mMYB101) resulted predominantly in plants that are indistinguishable from wild type. Plants that displayed altered morphological phenotypes were found to be ectopically expressing the mMYB101 transgene, and hence were misrepresentative of the in vivo functional role of miR159. CONCLUSIONS: This study presents a novel explanation for a paradox common to plant and animal miRNA systems, where among many potential miRNA-target relationships usually only a few appear physiologically relevant. The identification of a quiescent miR159c:target gene regulatory module in anthers provides a likely rationale for the presence of conserved miR159 binding sites in many targets for which miR159 regulation has no obvious functional role. Remnants from the demise of such modules may lead to an overestimation of miRNA regulatory complexity when investigated using bioinformatic, 5'-RACE or transgenic approaches. PMID- 21029442 TI - Evaluation of selected South African ethnomedicinal plants as mosquito repellents against the Anopheles arabiensis mosquito in a rodent model. AB - BACKGROUND: This study was initiated to establish whether any South African ethnomedicinal plants (indigenous or exotic), that have been reported to be used traditionally to repel or kill mosquitoes, exhibit effective mosquito repellent properties. METHODS: Extracts of a selection of South African taxa were tested for repellency properties in an applicable mosquito feeding-probing assay using unfed female Anopheles arabiensis. RESULTS: Although a water extract of the roots of Chenopodium opulifolium was found to be 97% as effective as DEET after 2 mins, time lag studies revealed a substantial reduction in efficacy (to 30%) within two hours. CONCLUSIONS: None of the plant extracts investigated exhibited residual repellencies >60% after three hours. PMID- 21029444 TI - Secular trend in candidemia and the use of fluconazole in Finland, 2004-2007. AB - BACKGROUND: In a previous study we observed an increasing trend in candidemia in Finland in the 1990s. Our aim was now to investigate further population-based secular trends, as well as outcome, and evaluate the association of fluconazole consumption and prophylaxis policy with the observed findings. METHODS: We analyzed laboratory-based surveillance data on candidemia from the National Infectious Diseases Register during 2004-2007 in Finland. Data on fluconazole consumption, expressed as defined daily doses, DDDs, was obtained from the National Agency for Medicines, and regional prophylaxis policies were assessed by a telephone survey. RESULTS: A total of 603 candidemia cases were identified. The average annual incidence rate was 2.86 cases per 100,000 population (range by year, 2.59-3.09; range by region, 2.37-3.85). The highest incidence was detected in males aged >65 years (12.23 per 100,000 population). Candida albicans accounted for 67% of cases, and C. glabrata ranked the second (19%), both without any significant change in proportions. C. parapsilosis accounted for 5% of cases and C. krusei 3% of cases. The one-month case-fatality varied between 28-32% during the study period. Fluconazole consumption increased from 19.57 DDDs per 100,000 population in 2000 to 25.09 in 2007. Systematic fluconazole prophylaxis was implemented for premature neonates, patients with acute leukemias and liver transplant patients. CONCLUSION: The dominant proportion of C. albicans remained stable, but C. glabrata was the most frequent non-albicans species. The proportion of C. glabrata had increased from our previous study period in the presence of increasing use of fluconazole. The rate of candidemia in Finland is still low but mortality high like in other countries. PMID- 21029443 TI - MicroRNAs in inflammatory lung disease--master regulators or target practice? AB - MicroRNAs (miRNAs) have emerged as a class of regulatory RNAs with immense significance in numerous biological processes. When aberrantly expressed miRNAs have been shown to play a role in the pathogenesis of several disease states. Extensive research has explored miRNA involvement in the development and fate of immune cells and in both the innate and adaptive immune responses whereby strong evidence links miRNA expression to signalling pathways and receptors with critical roles in the inflammatory response such as NF-kappaB and the toll-like receptors, respectively. Recent studies have revealed that unique miRNA expression profiles exist in inflammatory lung diseases such as cystic fibrosis, chronic obstructive pulmonary disease, asthma, idiopathic pulmonary fibrosis and lung cancer. Evaluation of the global expression of miRNAs provides a unique opportunity to identify important target gene sets regulating susceptibility and response to infection and treatment, and control of inflammation in chronic airway disorders. Over 800 human miRNAs have been discovered to date, however the biological function of the majority remains to be uncovered. Understanding the role that miRNAs play in the modulation of gene expression leading to sustained chronic pulmonary inflammation is important for the development of new therapies which focus on prevention of disease progression rather than symptom relief. Here we discuss the current understanding of miRNA involvement in innate immunity, specifically in LPS/TLR4 signalling and in the progression of the chronic inflammatory lung diseases cystic fibrosis, COPD and asthma. miRNA in lung cancer and IPF are also reviewed. PMID- 21029445 TI - Genomic analysis of microRNA time-course expression in liver of mice treated with genotoxic carcinogen N-ethyl-N-nitrosourea. AB - BACKGROUND: Dysregulated expression of microRNAs (miRNAs) has been previously observed in human cancer tissues and shown promise in defining tumor status. However, there is little information as to if or when expression changes of miRNAs occur in normal tissues after carcinogen exposure. RESULTS: To explore the possible time-course changes of miRNA expression induced by a carcinogen, we treated mice with one dose of 120 mg/kg N-ethyl-N-nitrosourea (ENU), a model genotoxic carcinogen, and vehicle control. The miRNA expression profiles were assessed in the mouse livers in a time-course design. miRNAs were isolated from the livers at days 1, 3, 7, 15, 30 and 120 after the treatment and their expression was determined using a miRNA PCR Array. Principal component analysis of the miRNA expression profiles showed that miRNA expression at post-treatment days (PTDs) 7 and 15 were different from those at the other time points and the control. The number of differentially expressed miRNAs (DEMs) changed over time (3, 5, 14, 32, 5 and 5 at PTDs 1, 3, 7, 15, 30 and 120, respectively). The magnitude of the expression change varied with time with the highest changes at PTDs 7 or 15 for most of the DEMs. In silico functional analysis of the DEMs at PTDs 7 and 15 indicated that the major functions of these ENU-induced DEMs were associated with DNA damage, DNA repair, apoptosis and other processes related to carcinogenesis. CONCLUSION: Our results showed that many miRNAs changed their expression to respond the exposure of the genotoxic carcinogen ENU and the number and magnitude of the changes were highest at PTDs 7 to 15. Thus, one to two weeks after the exposure is the best time for miRNA expression sampling. PMID- 21029446 TI - Electrophysiological evidence for abnormal preparatory states and inhibitory processing in adult ADHD. AB - BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder that starts in childhood and frequently persists in adults. Several theories postulate deficits in ADHD that have effects across many executive functions or in more narrowly defined aspects, such as response inhibition. Electrophysiological studies on children, however, indicate that ADHD is not associated with a core deficit of response inhibition, as abnormal inhibitory processing is typically preceded or accompanied by other processing deficits. It is not yet known if this pattern of abnormal processing is evident in adult ADHD. METHODS: The objective of this paper was to investigate event related potential indices of preparatory states and subsequent response inhibition processing in adults with ADHD. Two cued continuous performance tasks were presented to 21 adults meeting current criteria for adult ADHD and combined type ADHD in childhood, and 20 controls. RESULTS: The ADHD group exhibited significantly weaker orienting attention to cues, cognitive preparation processes and inhibitory processing. In addition, we observed a strong correlation between the resources allocated to orienting to cues and the strength of the subsequent response strength control processes, suggesting that orienting deficits partly predict and determine response control deficits in ADHD. CONCLUSIONS: These findings closely resemble those previously found in children with ADHD, which indicate that there is not a core response inhibition deficit in ADHD. These findings therefore suggest the possibility of developmental stability into adulthood of the underlying abnormal processes in ADHD. PMID- 21029447 TI - Correction: A cell-permeable dominant-negative survivin protein induces apoptosis and sensitizes prostate cancer cells to TNF-alpha therapy. PMID- 21029448 TI - It's not just about the park, it's about integration too: why people choose to use or not use urban greenspaces. AB - BACKGROUND: Greenspace has the potential to be a vital resource for promoting healthy living for people in urban areas, offering both opportunities for physical activity and wellbeing. Much research has explored the objectively measurable factors within areas to the end of explaining the role of greenspace access in continuing health inequalities. This paper explores the subjective reasons why people in urban areas choose to use, or not use, local public greenspace. METHODS: In-depth interviews with 24 people living in two areas of Glasgow, United Kingdom were conducted, supplemented with participant photography and participatory methods. Data was thematically categorised to explore subjectively experienced facilitators and barriers to greenspace use in urban areas. RESULTS: From the perspective of current and potential urban greenspace users, access is revealed to be about more than the physical characteristics of neighbourhoods, greenspace resources or objectively measurable features of walkability and connectivity. Subjectively, the idea of walkability includes perceptions of social cohesion at a community level and the level of felt integration and inclusion by individuals in their communities. Individual's feelings of integration and inclusion potentially mitigate the effects of experiential barriers to urban greenspace access, such as evidence of anti-social behaviour. CONCLUSIONS: We conclude that improving access to greenspace for all in urban communities will require more than providing high quality resources such as parks, footpaths, activities and lighting. Physical availability interacts with community contexts already established and a holistic understanding of access is required. A key cultural component of areas and neighbourhoods is the level of social cohesion, a factor that has the potential to reinforce existing health inequalities through shaping differentiated greenspace access between subgroups of the local population. PMID- 21029449 TI - Sexual coercion of married women in Nepal. AB - BACKGROUND: Sexual coercion is an important public health issue due to its negative association with social and health outcomes. The paper aims to examine the prevalence of sexual coercion perpetrated by husbands on their wives in Nepal and to identify the characteristics associated with this phenomenon. METHODS: The data used in this paper comes from a cross-sectional survey on "Domestic Violence in Nepal" carried out in 2009. A total of 1,536 married women were interviewed and associations between sexual coercion and the explanatory variables were assessed via bivariate analysis using Chi-square tests. Logistic regression was then applied to assess the net effect of several independent variables on sexual coercion. RESULTS: Overall, about three in five women (58%) had experienced some form of sexual coercion by their husbands. Logistic regression analysis found that the literacy status of women, decision-making power regarding their own health care, husband-wife age differences, alcohol consumption by the husband, and male patriarchal control all had significant associations with women's experience of sexual coercion. Literate women had 28% less chance (adjusted odds ratio (aOR) = 0.72) of experiencing sexual coercion by their husbands than did illiterate women. Women who made decisions jointly with their husbands with regard to their own health care were 36% less likely (aOR = 0.64) to experience sexual coercion than those whose health care was decided upon by their mothers/fathers-in-law. On the other hand, women whose husbands were 5 or more years older than they were more likely to report sexual coercion (aOR = 1.33) than were their counterparts, as were women whose husbands consumed alcohol (aOR = 1.27). Furthermore, women who experienced higher levels of patriarchal control from their husbands were also more likely to experience sexual coercion by their husbands (aOR = 7.2) compared to those who did not face such control. CONCLUSION: The study indicates that sexual coercion among married women is widespread in Nepal. Programs should focus on education and women's empowerment to reduce sexual coercion and protect women's health and rights. Furthermore, campaigns against alcohol abuse and awareness programs targeting husbands should also focus attention on the issue of sexual coercion. PMID- 21029450 TI - A reliable measure of frailty for a community dwelling older population. AB - BACKGROUND: Frailty remains an elusive concept despite many efforts to define and measure it. The difficulty in translating the clinical profile of frail elderly people into a quantifiable assessment tool is due to the complex and heterogeneous nature of their health problems. Viewing frailty as a 'latent vulnerability' in older people this study aims to derive a model based measurement of frailty and examines its internal reliability in community dwelling elderly. METHOD: The British Women's Heart and Health Study (BWHHS) cohort of 4286 women aged 60-79 years from 23 towns in Britain provided 35 frailty indicators expressed as binary categorical variables. These indicators were corrected for measurement error and assigned relative weights in its association with frailty. Exploratory factor analysis (EFA) reduced the data to a smaller number of factors and was subjected to confirmatory factor analysis (CFA) which restricted the model by fitting the EFA-driven structure to observed data. Cox regression analysis compared the hazard ratios for adverse outcomes of the newly developed British frailty index (FI) with a widely known FI. This process was replicated in the MRC Assessment study of older people, a larger cohort drawn from 106 general practices in Britain. RESULTS: Seven factors explained the association between frailty indicators: physical ability, cardiac symptoms/disease, respiratory symptoms/disease, physiological measures, psychological problems, co-morbidities and visual impairment. Based on existing concepts and statistical indices of fit, frailty was best described using a General Specific Model. The British FI would serve as a better population metric than the FI as it enables people with varying degrees of frailty to be better distinguished over a wider range of scores. The British FI was a better independent predictor of all-cause mortality, hospitalization and institutionalization than the FI in both cohorts. CONCLUSIONS: Frailty is a multidimensional concept represented by a wide range of latent (not directly observed) attributes. This new measure provides more precise information than is currently recognized, of which cluster of frailty indicators are important in older people. This study could potentially improve quality of life among older people through targeted efforts in early prevention and treatment of frailty. PMID- 21029451 TI - A bacteria-specific 2[4Fe-4S] ferredoxin is essential in Pseudomonas aeruginosa. AB - BACKGROUND: Ferredoxins are small iron-sulfur proteins belonging to all domains of life. A sub-group binds two [4Fe-4S] clusters with unequal and extremely low values of the reduction potentials. These unusual properties are associated with two specific fragments of sequence. The functional importance of the very low potential ferredoxins is unknown. RESULTS: A bioinformatic screening of the sequence features defining very low potential 2[4Fe-4S] ferredoxins has revealed the almost exclusive presence of the corresponding fdx gene in the Proteobacteria phylum, without occurrence in Archaea and Eukaryota. The transcript was found to be monocistronic in Pseudomonas aeruginosa, and not part of an operon in most bacteria. Only fdx genes of bacteria which anaerobically degrade aromatic compounds belong to operons. As this pathway is not present in all bacteria having very low potential 2[4Fe-4S] ferredoxins, these proteins cannot exclusively be reductants of benzoyl CoA reductases. Expression of the ferredoxin gene did not change in response to varying growth conditions, including upon macrophage infection or aerobic growth with 4-hydroxy benzoate as carbon source. However, it increased along the growth curve in Pseudomonas aeruginosa and in Escherichia coli. The sequence immediately 5' upstream of the coding sequence contributed to the promotor activity. Deleting the fdx gene in Pseudomonas aeruginosa abolished growth, unless a plasmid copy of the gene was provided to the deleted strain. CONCLUSIONS: The gene of the very low potential 2[4Fe-4S] ferredoxin displays characteristics of a housekeeping gene, and it belongs to the minority of genes that are essential in Pseudomonas aeruginosa. These data identify a new potential antimicrobial target in this and other pathogenic Proteobacteria. PMID- 21029452 TI - Infection control and the burden of tuberculosis infection and disease in health care workers in china: a cross-sectional study. AB - BACKGROUND: Hospitals with inadequate infection control are risky environments for the emergence and transmission of tuberculosis (TB). We evaluated TB infection control practices, and the prevalence of latent TB infection (LTBI) and TB disease and risk factors in health care workers (HCW) in TB centers in Henan province in China. METHODS: A cross-sectional survey was conducted in 2005. To assess TB infection control practices in TB centers, checklists were used. HCW were tuberculin skin tested (TST) to measure LTBI prevalence, and were asked for sputum smears and chest X-rays to detect TB disease, and questionnaires to assess risk factors. Differences between groups for categorical variables were analyzed by binary logistic regression. The clustered design of the study was taken into account by using a multilevel logistic model. RESULTS: The assessment of infection control practices showed that only in a minority of the centers the patient consultation areas and X-ray areas were separated from the waiting areas and administrative areas. Mechanical ventilation was not available in any of the TB centers. N95 respirators were not available for HCW and surgical masks were not available for TB patients and suspects. The LTBI prevalence of HCW with and without BCG scar was 55.6% (432/777) and 49.0% (674/1376), respectively (P = 0.003). Older HCW, HCW with longer duration of employment, and HCW who worked in departments with increased contact with TB patients had a higher prevalence of LTBI. HCW who work in TB centers at the prefecture level, or with an inpatient ward also had a higher prevalence of LTBI. Twenty cases of pulmonary TB were detected among 3746 HCW. The TB prevalence was 6.7/1000 among medical staff and 2.5/1000 among administrative/logistic staff. CONCLUSION: TB infection control in TB centers in Henan, China, appears to be inadequate and the prevalence of LTBI and TB disease among HCW was high. TB infection control practices in TB centers should be strengthened in China, including administrative measures, renovation of buildings, and use of respirators and masks. Regular screening of HCW for TB disease and LTBI needs to be considered, offering preventive therapy to those with TST conversions. PMID- 21029453 TI - Analysis of the expression profile of Dickkopf-1 gene in human glioma and the association with tumor malignancy. AB - BACKGROUND: Gliomas represent the most common primary malignant brain tumors, yet little is known about the molecular pathogenesis of these tumors. The highly regulated Wnt signal transduction pathway is essential for normal developmental processes, and defects in the pathway are closely linked to oncogenesis. Dickkopf 1 (DKK-1) is a secreted protein that acts as a potent inhibitor of the Wnt pathway. The aim of this study was to examine the expression profile of DKK-1 gene in human glioma and its association with tumor malignancy. METHODS: We determined the expression levels of DKK-1 transcript and protein in 12 glioblastoma cell lines, medulloblastoma cells, low-grade glioma cells, and human astrocyte cells by semiquantitative RT-PCR and ELISA. A total of 47 tumor biopsy specimens and 11 normal brain tissue samples from patients with cerebral trauma internal decompression were embedded in paraffin blocks and used for immunostaining. Twenty-six primary tumors and 7 corresponding brain samples were stored in liquid nitrogen and used for RT-PCR. We further examined serologic concentrations and cerebral fluid levels of DKK-1 in patients with tumors. RESULTS: DKK-1 could only be detected in 12 human glioblastoma cell lines, not in a panel of other tumor and normal cell lines. The difference between glioma patients and healthy individuals was significant. Kendall's tau-c association analysis also revealed the increased DKK-1 protein expression in tumor tissues of higher pathologic classification. The levels of cerebral fluid DKK-1 protein were significantly higher in glioma patients than in healthy donors or in neuronal benign tumor patients, suggesting that the DKK-1 molecule in cerebral fluids can be applicable to detect the presence of glioma and be developed as a novel prognostic treatment. CONCLUSION: The Wnt antagonist DKK-1 gene may have important roles in glioma tumorigenesis and act as a novel biomarker in human malignant glioblastoma. PMID- 21029454 TI - Evaluation of a magnetic resonance-compatible dentoalveolar tactile stimulus device. AB - BACKGROUND: Few methods exist to study central nervous system processes following dentoalveolar tactile stimulation using functional magnetic resonance imaging (fMRI), likely due to inherent technical difficulties. Our primary goal was to develop and perform feasibility testing of a novel device capable of delivering valid and reliable dentoalveolar stimuli at dental chair-side and during MRI. Details of a device designed to deliver dentoalveolar dynamic pressure stimuli are described. Device testing took place in three settings: a) laboratory testing to assess range of stimulus force intensities, b) dental chair-side to assess reliability, validity and discriminant ability in force-pain relationship; and c) MRI to evaluate magnetic compatibility and ability to evoke brain activation in painfree subjects similar to those described in the literature. RESULTS: A novel device capable of delivering valid and reliable dentoalveolar somatosensory stimulation was developed (ICC = 0.89, 0.78-1 [95% CI]). Psychophysical data analysis showed high discriminant ability in differentiating painfree controls from cases with chronic dentoalveolar pain related to deafferenting dental procedures (sensitivity = 100%, specificity = 86.7%, area under ROC curve = 0.99). FMRI results of dentoalveolar dynamic pressure pain in painfree subjects revealed activation of brain areas typically associated with acute pain processing including thalamus, primary/secondary somatosensory, insular and prefrontal cortex. CONCLUSIONS: A novel psychophysical method to deliver dynamic dentoalveolar pressure stimulation was developed and validated, allowing non invasive MRI-based exploration of central nervous system function in response to intraoral somatosensation. BACKGROUND: The organization of the trigeminal system is unique as it provides somatosensory innervation to the face, masticatory and oral structures, the majority of the intracranial contents 1 and to specialized structures (tongue, nasal mucosa, auricle, tympanic membrane, cornea and part of the conjunctiva) 2. Somatic sensory information transmitted by the trigeminal nerve is crucial for normal orofacial function; however, the mechanisms of many chronic pain conditions affecting areas innervated by this sensory system are not well understood 345. The clinical presentation of chronic intraoral pain in the area of a tooth or in a site formally occupied by a tooth with no clinical or radiological signs of pathology, referred to as atypical odontalgia (AO) 67, is one such chronic pain condition of particular interest to dentists that is difficult to diagnose and manage. Recent research suggests both peripheral and central nervous system mechanisms being involved in AO pathophysiology 8910, but the majority of mechanism-based research of patients with AO has focused on the "peripheral aspect" 7.Functional magnetic resonance imaging (fMRI) is an established research technique to study the central aspects of pain 11. Of existing neuroimaging techniques, fMRI provides good spatial resolution of cortical and subcortical structures critical in the processing of nociception, acceptable temporal resolution, does not involve ionizing radiation, and can be performed using most MRI systems that already exist in research centers and the community. For these reasons, we sought to develop a protocol that allows us to use this tool to investigate the central mechanisms involved in the processes of intraoral pain arising from the dentoalveolar region. Using this device, our long term objective is to improve our understanding of the underlying mechanisms of persistent dentoalveolar pain.In the past few years several studies used fMRI to investigate the human trigeminal system 1213, with a limited subset focusing on intraoral stimulation - specifically on the dentoalveolar processes, such as lip, tongue and teeth stimulation 14 or only teeth 151617. Some reasons for scarce literature on this topic may be the technical challenges involved in delivering facial/intraoral stimulation inside a MR scanner 1718: possibility of magnetic interference, detriment of image quality, subject discomfort and reduced working space between the subject's head and the radiofrequency coil. As a consequence a MR-compatible device would need to not only overcome these challenges but also be capable of delivering a controlled and reproducible stimuli 19, as reliability/reproducibility is a necessary feature of sensory testing 20.Existing MR-compatible methods of dentoalveolar stimulation are limited and do not adequately deliver stimuli across a range of non-painful to painful intensities and/or cannot be adjusted to reach posterior aspects of the dentoalveolar region. Therefore our goal was to develop and test the feasibility of a device able to: 1) provide reliable and valid dentoalveolar stimuli, 2) deliver such stimulation within the restricted space of an MR head coil, 3) be compatible for use within an MR environment, and 4) produce brain activation in painfree controls consistent to those observed by others using fMRI. PMID- 21029455 TI - Preferences for active and aggressive intervention among patients with advanced cancer. AB - BACKGROUND: Intrinsic to "Patient-Centered Care" is being respectful and responsive to individual patient preferences, expressed needs, and personal values. Establishing a patient's preferences for active and aggressive intervention is imperative and foundational to the development of advance care planning. With the increasing awareness and acceptance of palliative philosophies of care, patients with advanced cancer are increasingly transitioning from active and aggressive medical management (AAMM) to conservative palliative management (CPM). METHODS: A cross-sectional study based on a prospective and sequential case series of patients referred to a regional palliative medicine consultative program was assembled between May 1, 2005 and June 30, 2006. Patients and/or their substitute decision makers (SDM) completed a questionnaire, at baseline, that assessed their preferences for AAMM en route to their eventual deaths. Seven common interventions constituting AAMM were surveyed: cardiopulmonary resuscitation (CPR) & mechanical ventilation (MV), chemotherapy, antibiotics, anticoagulants, blood transfusions, feeding tubes, and artificial hydration. Multivariable analyses were conducted on the seven interventions individually as well as on the composite score that summed preferences for the seven interventions. RESULTS: 380 patients with advanced cancer agreed to participate in the study. A trend to desire a mostly conservative palliative approach was noted as 42% of patients desired one or fewer interventions. At baseline, most patients and their SDM's were relatively secure about decisions pertaining to the seven interventions as the rates of being "undecided" ranged from a high of 23.4% for chemotherapy to a low of 3.9% for feeding tubes. Multivariable modeling showed that more AAMM was preferred by younger patients (P < 0.0001), non Caucasians (P = 0.042), patients with higher baseline Palliative Performance Scale scores (P = 0.0002) and where a SDM was involved in the decision process (p = 0.027). Non-statistically significant trends to prefer more AAMM was observed with male gender (p = 0.077) and higher levels of the Charlson Comorbidity index (p = 0.059). There was no association between treatment preferences and cancer class. CONCLUSIONS: Although the majority of patients with advanced cancer in this study expressed preferences for CPM, younger age, higher baseline PPSv2, and involvement of SDMs in the decision process were significantly associated with preferences for AAMM. PMID- 21029456 TI - Selective activity of extracts of Margaritaria discoidea and Homalium africanum on Onchocerca ochengi. AB - BACKGROUND: The current treatment of onchocerciasis relies on the use of ivermectin which is only microfilaricidal and for which resistant parasite strains of veterinary importance are increasingly being detected. In the search for novel filaricides and alternative medicines, we investigated the selective activity of crude extracts of Margaritaria discoidea and Homalium africanum on Onchocerca ochengi, a model parasite for O. volvulus. These plants are used to treat the disease in North West Cameroon. METHODS: Sixteen crude extracts were prepared from various parts of M. discoidea and H. africanum using different organic solvents. The filaricidal activities were determined in vitro. Cytotoxicity of the active extracts was assessed on monkey kidney epithelial cells in vitro and the selectivity indices (SI) of the extracts determined. Acute toxicity of the promising extracts was investigated in mice. RESULTS: Four out of the 16 extracts showed microfilaricidal activity based on motility reduction, whereas, none showed macrofilaricidal activity based on the MTT/formazan assay. The methylene chloride extract of H. africanum leaves (HLC) recorded the lowest IC50 of 31.25 MUg/mL and an IC100 of 62.5 MUg/mL. The SI for the active extracts ranged from 0.5 - 2.63. No form of acute toxicity was observed in mice. Phytochemical analysis revealed the presence of anthraquinones, sterols and terpenoids in the promising extracts. CONCLUSIONS: The non-polar extracts of M. discoidea and H. africanum are potential sources of new microfilaricidal lead compounds, and the results support their use in traditional medicine. PMID- 21029457 TI - Uncoupling protein 2 G(-866)A polymorphism: a new gene polymorphism associated with C-reactive protein in type 2 diabetic patients. AB - BACKGROUND: This study evaluated the relationship between the G(-866)A polymorphism of the uncoupling protein 2 (UCP2) gene and high-sensitivity C reactive protein (hs-CRP) plasma levels in diabetic patients. METHODS: We studied 383 unrelated people with type 2 diabetes aged 40-70 years. Anthropometry, fasting lipids, glucose, HbA1c, and hs-CRP were measured. Participants were genotyped for the G (-866)A polymorphism of the uncoupling protein 2 gene. RESULTS: Hs-CRP (mg/L) increased progressively across the three genotype groups AA, AG, or GG, being respectively 3.0 +/- 3.2, 3.6 +/- 5.0, and 4.8 +/- 5.3 (p for trend = 0.03). Since hs-CRP values were not significantly different between AA and AG genotype, these two groups were pooled for further analyses. Compared to participants with the AA/AG genotypes, homozygotes for the G allele (GG genotype) had significantly higher hs-CRP levels (4.8 +/- 5.3 vs 3.5 +/- 4.7 mg/L, p = 0.01) and a larger proportion (53.9% vs 46.1%, p = 0.013) of elevated hs-CRP (> 2 mg/L). This was not explained by major confounders such as age, gender, BMI, waist circumference, HbA1c, smoking, or medications use which were comparable in the two genotype groups. CONCLUSIONS: The study shows for the first time, in type 2 diabetic patients, a significant association of hs-CRP levels with the G(-866)A polymorphism of UCP2 beyond the effect of major confounders. PMID- 21029458 TI - Resveratrol represses YKL-40 expression in human glioma U87 cells. AB - BACKGROUND: Glioblastoma multiforme (GBM) is the most malignant intracranial tumour that develops in both adults and children. Microarray gene analyses have confirmed that the human YKL-40 gene is one of the most over-expressed genes in these tumours but not in normal brain tissue. Clinical studies have shown that serum YKL-40 levels are positively correlated with tumour burden in addition to being an independent prognostic factor of a short relapse-free interval as well as short overall survival in patients with various cancers. Our previous study revealed that YKL-40 was closely correlated with the pathological grades of human primary astrocytomas and played a crucial role in glioma cell proliferation. Hence, YKL-40 could be an attractive target in the design of anti-cancer therapies. METHODS: Cell viability and invasion assays were performed to detect the cell proliferation and invasive ability of U87 cells induced by resveratrol (3, 5, 4'-trihydroxystilbene; Res) or YKL-40 small-interfering RNAs (siRNAs). In addition, the luciferase assay, real-time RT-PCR, western blotting, and ELISA were used to measure YKL-40 promoter activity, mRNA, and protein expression, respectively. The expressions of phosphor-ERK1/2 and ERK1/2 were determined by western blotting. RESULTS: Res inhibited U87 cell proliferation and invasion in vitro and repressed YKL-40 in U87 cells by decreasing the activity of its promoter and reducing mRNA transcription and protein expression in vitro. YKL-40 siRNA treatment also impaired the invasiveness of U87 cells. When U87 cells were cultured with 20 MUM PD98059 (an ERK1/2 inhibitor) alone, with 20 MUM PD98059 and 100 MUM Res, or with 100 MUM Res alone for 48 h, YKL-40 protein expression decreased most significantly in the Res-treated group. PD98059 partially reversed the decrease of YKL-40 protein expression induced by Res. Furthermore, phosphor ERK1/2 expression was reduced by Res treatment in a time-dependent manner. CONCLUSIONS: We demonstrated for the first time that Res represses YKL-40 expression in vitro; in addition, the ERK1/2 pathway is involved in this repression. This finding could extend the prospective use of Res in glioma research and enlarge the armamentarium for treating gliomas. PMID- 21029459 TI - Expression of human A53T alpha-synuclein in the rat substantia nigra using a novel AAV1/2 vector produces a rapidly evolving pathology with protein aggregation, dystrophic neurite architecture and nigrostriatal degeneration with potential to model the pathology of Parkinson's disease. AB - BACKGROUND: The pathological hallmarks of Parkinson's disease (PD) include the presence of alpha-synuclein (alpha-syn) rich Lewy bodies and neurites and the loss of dopaminergic (DA) neurons of the substantia nigra (SN). Animal models of PD based on viral vector-mediated over-expression of alpha-syn have been developed and show evidence of DA toxicity to varying degrees depending on the type of virus used, its concentration, and the serotype of vector employed. To date these models have been variable, difficult to reproduce, and slow in their evolution to achieve a desired phenotype, hindering their use as a model for testing novel therapeutics. To address these issues we have taken a novel vector in this context, that can be prepared in high titer and which possesses an ability to produce neuronally-directed expression, with expression dynamics optimised to provide a rapid rise in gene product expression. Thus, in the current study, we have used a high titer chimeric AAV1/2 vector, to express human A53T alpha-syn, an empty vector control (EV), or green fluorescent protein (GFP), the latter to control for the possibility that high levels of protein in themselves might contribute to damage. RESULTS: We show that following a single 2 MUl injection into the rat SN there is near complete coverage of the structure and expression of A53T alpha-syn or GFP appears throughout the striatum. Within 3 weeks of SN delivery of their respective vectors, aggregations of insoluble alpha syn were observed in SN DA neurons. The numbers of DA neurons in the SN were significantly reduced by expression of A53T alpha-syn (52%), and to a lesser extent by GFP (24%), compared to EV controls (both P < 0.01). At the level of the striatum, AAV1/2-A53T alpha-syn injection produced dystrophic neurites and a significant reduction in tyrosine hydroxylase levels (by 53%, P < 0.01), this was not seen in the AAV1/2-GFP condition. CONCLUSIONS: In the current implementation of the model, we recapitulate the primary pathological hallmarks of PD, although a proportion of the SN damage may relate to general protein overload and may not be specific for A53T alpha-syn. Future studies will thus be required to optimise the dose of AAV1/2 employed before fully characterizing this model. The dynamics of the evolution of the pathology however, provide advantages over current models with respect to providing an initial screen to assess efficacy of novel treatments that might prevent/reverse alpha-syn aggregation. PMID- 21029460 TI - Hyperoncotic colloids and acute kidney injury: a meta-analysis of randomized trials. AB - INTRODUCTION: It has been hypothesized that hyperoncotic colloids might contribute to acute kidney injury (AKI). However, the validity of this hypothesis remains unclear. METHODS: A meta-analysis was conducted of randomized controlled trials evaluating AKI after infusion of hyperoncotic albumin and hydroxyethyl starch (HES) solutions. Mortality was a secondary endpoint. Eligible trials were sought by multiple methods, and the pooled odds ratios (OR) for AKI and death and 95% confidence intervals (CI) were computed under a random effects model. RESULTS: Eleven randomized trials with a total of 1220 patients were included: 7 evaluating hyperoncotic albumin and 4 hyperoncotic HES. Clinical indications were ascites, surgery, sepsis and spontaneous bacterial peritonitis. Hyperoncotic albumin decreased the odds of AKI by 76% (OR, 0.24; CI, 0.12-0.48; P < 0.0001), while hyperoncotic HES increased those odds by 92% (OR, 1.92; CI, 1.31-2.81; P = 0.0008). Parallel effects on mortality were observed, with hyperoncotic albumin reducing the odds of death by 48% (OR, 0.52; CI, 0.28-0.95; P = 0.035) and hyperoncotic HES raising those odds by 41% (OR, 1.41; CI, 1.01-1.96; P = 0.043). CONCLUSIONS: This meta-analysis does not support the hypothesis that hyperoncotic colloid solutions per se injure the kidney. Renal effects appear instead to be colloid-specific, with albumin displaying renoprotection and HES showing nephrotoxicity. PMID- 21029461 TI - Laparoscopic and open resection for colorectal cancer: an evaluation of cellular immunity. AB - BACKGROUND: Colorectal cancer is one kind of frequent malignant tumors of the digestive tract which gets high morbidity and mortality allover the world. Despite the promising clinical results recently, less information is available regarding the perioperative immunological effects of laparoscopic surgery when compared with the open surgery. This study aimed to compare the cellular immune responses of patients who underwent laparoscopic (LCR) and open resections (OCR) for colorectal cancer. METHODS: Between Mar 2009 and Sep 2009, 35 patients with colorectal carcinoma underwent LCR by laparoscopic surgeon. These patients were compared with 33 cases underwent conventional OCR by colorectal surgeon. Clinical data about the patients were collected prospectively. Comparison of the operative details and postoperative outcomes between laparoscopic and open resection was performed. Peripheral venous blood samples from these 68 patients were taken prior to surgery as well as on postoperative days (POD) 1, 4 and 7. Cell counts of total white blood cells, neutrophils, lymphocyte subpopulations, natural killer (NK) cells as well as CRP were determined by blood counting instrument, flow cytometry and hematology analyzer. RESULTS: There was no difference in the age, gender and tumor status between the two groups. The operating time was a little longer in the laparoscopic group (P > 0.05), but the blood loss was less (P = 0.039). Patients with laparoscopic resection had earlier return of bowel function and earlier resumption of diet as well as shorter median hospital stay (P < 0.001). Compared with OCR group, cell numbers of total lymphocytes, CD4+T cells and CD8+T cells were significant more in LCR group (P < 0.05) on POD 4, while there was no difference in the CD45RO+T or NK cell numbers between the two groups. Cellular immune responds were similar between the two groups on POD1 and POD7. CONCLUSIONS: Laparoscopic colorectal resection gets less surgery stress and short-term advantages compared with open resection. Cellular immune respond appears to be less affected by laparoscopic colorectal resection when compared with open resection. PMID- 21029462 TI - Spiral ligament fibrocyte-derived MCP-1/CCL2 contributes to inner ear inflammation secondary to nontypeable H. influenzae-induced otitis media. AB - BACKGROUND: Otitis media (OM), one of the most common pediatric infectious diseases, causes inner ear inflammation resulting in vertigo and sensorineural hearing loss. Previously, we showed that spiral ligament fibrocytes (SLFs) recognize OM pathogens and up-regulate chemokines. Here, we aim to determine a key molecule derived from SLFs, contributing to OM-induced inner ear inflammation. METHODS: Live NTHI was injected into the murine middle ear through the tympanic membrane, and histological analysis was performed after harvesting the temporal bones. Migration assays were conducted using the conditioned medium of NTHI-exposed SLFs with and without inhibition of MCP-1/CCL2 and CCR2. qRT-PCR analysis was performed to demonstrate a compensatory up-regulation of alternative genes induced by the targeting of MCP-1/CCL2 or CCR2. RESULTS: Transtympanic inoculation of live NTHI developed serous and purulent labyrinthitis after clearance of OM. THP-1 cells actively migrated and invaded the extracellular matrix in response to the conditioned medium of NTHI-exposed SLFs. This migratory activity was markedly inhibited by the viral CC chemokine inhibitor and the deficiency of MCP-1/CCL2, indicating that MCP-1/CCL2 is a main attractant of THP 1 cells among the SLF-derived molecules. We further demonstrated that CCR2 deficiency inhibits migration of monocyte-like cells in response to NTHI-induced SLF-derived molecules. Immunolabeling showed an increase in MCP-1/CCL2 expression in the cochlear lateral wall of the NTHI-inoculated group. Contrary to the in vitro data, deficiency of MCP-1/CCL2 or CCR2 did not inhibit OM-induced inner ear inflammation in vivo. We demonstrated that targeting MCP-1/CCL2 enhances NTHI induced up-regulation of MCP-2/CCL8 in SLFs and up-regulates the basal expression of CCR2 in the splenocytes. We also found that targeting CCR2 enhances NTHI induced up-regulation of MCP-1/CCL2 in SLFs. CONCLUSIONS: Taken together, we suggest that NTHI-induced SLF-derived MCP-1/CCL2 is a key molecule contributing to inner ear inflammation through CCR2-mediated recruitment of monocytes. However, deficiency of MCP-1/CCL2 or CCR2 alone was limited to inhibit OM-induced inner ear inflammation due to compensation of alternative genes. PMID- 21029464 TI - Factors influencing success in quality-improvement collaboratives: development and psychometric testing of an instrument. AB - BACKGROUND: To increase the effectiveness of quality-improvement collaboratives (QICs), it is important to explore factors that potentially influence their outcomes. For this purpose, we have developed and tested the psychometric properties of an instrument that aims to identify the features that may enhance the quality and impact of collaborative quality-improvement approaches. The instrument can be used as a measurement instrument to retrospectively collect information about perceived determinants of success. In addition, it can be prospectively applied as a checklist to guide initiators, facilitators, and participants of QICs, with information about how to perform or participate in a collaborative with theoretically optimal chances of success. Such information can be used to improve collaboratives. METHODS: We developed an instrument with content validity based on literature and the opinions of QIC experts. We collected data from 144 healthcare professionals in 44 multidisciplinary improvement teams participating in two QICs and used exploratory factor analysis to assess the construct validity. We used Cronbach's alpha to ascertain the internal consistency. RESULTS: The 50-item instrument we developed reflected expert-opinion-based determinants of success in a QIC. We deleted nine items after item reduction. On the basis of the factor analysis results, one item was dropped, which resulted in a 40-item questionnaire. Exploratory factor analysis showed that a three-factor model provided the best fit. The components were labeled 'sufficient expert team support', 'effective multidisciplinary teamwork', and 'helpful collaborative processes'. Internal consistency reliability was excellent (alphas between .85 and .89). CONCLUSIONS: This newly developed instrument seems a promising tool for providing healthcare workers and policy makers with useful information about determinants of success in QICs. The psychometric properties of the instrument are satisfactory and warrant application either as an objective measure or as a checklist. PMID- 21029463 TI - Gender differences in self reported long term outcomes following moderate to severe traumatic brain injury. AB - BACKGROUND: The majority of research on health outcomes after a traumatic brain injury is focused on male participants. Information examining gender differences in health outcomes post traumatic brain injury is limited. The purpose of this study was to investigate gender differences in symptoms reported after a traumatic brain injury and to examine the degree to which these symptoms are problematic in daily functioning. METHODS: This is a secondary data analysis of a retrospective cohort study of 306 individuals who sustained a moderate to severe traumatic brain injury 8 to 24 years ago. Data were collected using the Problem Checklist (PCL) from the Head Injury Family Interview (HIFI). Using Bonferroni correction, group differences between women and men were explored using Chi square and Wilcoxon analysis. RESULTS: Chi-square analysis by gender revealed that significantly more men reported difficulty setting realistic goals and restlessness whereas significantly more women reported headaches, dizziness and loss of confidence. Wilcoxon analysis by gender revealed that men reported sensitivity to noise and sleep disturbances as significantly more problematic than women, whereas for women, lack of initiative and needing supervision were significantly more problematic in daily functioning. CONCLUSION: This study provides insight into gender differences on outcomes after traumatic brain injury. There are significant differences between problems reported by men compared to women. This insight may facilitate health service planners and clinicians when developing programs for individuals with brain injury. PMID- 21029465 TI - Contrasting population genetic patterns within the white-throated sparrow genome (Zonotrichia albicollis). AB - BACKGROUND: The level of nucleotide diversity observed across the genome is positively correlated with the local rate of recombination. Avian karyotypes are typified by large variation in chromosome size and the rate of recombination in birds has been shown to be negatively correlated with chromosome size. It has thus been predicted that nucleotide diversity is negatively correlated with chromosome size in aves. However, there is limited empirical evidence to support this prediction. RESULTS: Here we sequenced 27 autosomal and 12 sex chromosome linked loci in the white-throated sparrow (Zonotrichia albicollis) to quantify and compare patterns of recombination, linkage disequilibrium (LD), and genetic diversity across the genome of this North American songbird. Genetic diversity on the autosomes varied up to 8-fold, with the lowest diversity observed on the macrochromosomes and the highest diversity on the microchromosomes. Genetic diversity on the sex chromosomes was reduced compared to the autosomes, the most extreme difference being a ~300-fold difference between the W chromosome and the microchromosomes. LD and population structure associated with a common inversion polymorphism (ZAL2/2m) in this species were found to be atypical compared to other macrochromosomes, and nucleotide diversity within this inversion on the two chromosome arrangements was more similar to that observed on the Z chromosome. CONCLUSIONS: A negative correlation between nucleotide diversity and autosome size was observed in the white-throated sparrow genome, as well as low levels of diversity on the sex chromosomes comparable to those reported in other birds. The population structure and extended LD associated with the ZAL2/2m chromosomal polymorphism are exceptional compared to the rest of the white-throated sparrow genome. PMID- 21029466 TI - A randomised clinical trial of intrapartum fetal monitoring with computer analysis and alerts versus previously available monitoring. AB - BACKGROUND: Intrapartum fetal hypoxia remains an important cause of death and permanent handicap and in a significant proportion of cases there is evidence of suboptimal care related to fetal surveillance. Cardiotocographic (CTG) monitoring remains the basis of intrapartum surveillance, but its interpretation by healthcare professionals lacks reproducibility and the technology has not been shown to improve clinically important outcomes. The addition of fetal electrocardiogram analysis has increased the potential to avoid adverse outcomes, but CTG interpretation remains its main weakness. A program for computerised analysis of intrapartum fetal signals, incorporating real-time alerts for healthcare professionals, has recently been developed. There is a need to determine whether this technology can result in better perinatal outcomes. METHODS/DESIGN: This is a multicentre randomised clinical trial. Inclusion criteria are: women aged >= 16 years, able to provide written informed consent, singleton pregnancies >= 36 weeks, cephalic presentation, no known major fetal malformations, in labour but excluding active second stage, planned for continuous CTG monitoring, and no known contra-indication for vaginal delivery. Eligible women will be randomised using a computer-generated randomisation sequence to one of the two arms: continuous computer analysis of fetal monitoring signals with real-time alerts (intervention arm) or continuous CTG monitoring as previously performed (control arm). Electrocardiographic monitoring and fetal scalp blood sampling will be available in both arms. The primary outcome measure is the incidence of fetal metabolic acidosis (umbilical artery pH < 7.05, BDecf > 12 mmol/L). Secondary outcome measures are: caesarean section and instrumental vaginal delivery rates, use of fetal blood sampling, 5-minute Apgar score < 7, neonatal intensive care unit admission, moderate and severe neonatal encephalopathy with a marker of hypoxia, perinatal death, rate of internal monitoring, tracing quality, and signal loss. Analysis will follow an intention to treat principle. Incidences of primary and secondary outcomes will be compared between groups. Assuming a reduction in metabolic acidosis from 2.8% to 1.8%, using a two-sided test with alpha = 0.05, power = 0.80, and 10% loss to follow up, 8133 women need to be randomised. DISCUSSION: This study will provide evidence of the impact of intrapartum monitoring with computer analysis and real time alerts on the incidence of adverse perinatal outcomes, intrapartum interventions and signal quality. (Current controlled trials ISRCTN42314164). PMID- 21029467 TI - The Nutrition and Enjoyable Activity for Teen Girls (NEAT girls) randomized controlled trial for adolescent girls from disadvantaged secondary schools: rationale, study protocol, and baseline results. AB - BACKGROUND: Child and adolescent obesity predisposes individuals to an increased risk of morbidity and mortality from a range of lifestyle diseases. Although there is some evidence to suggest that rates of pediatric obesity have leveled off in recent years, this has not been the case among youth from low socioeconomic backgrounds. The purpose of this paper is to report the rationale, study design and baseline findings of a school-based obesity prevention program for low-active adolescent girls from disadvantaged secondary schools. METHODS/DESIGN: The Nutrition and Enjoyable Activity for Teen Girls (NEAT Girls) intervention will be evaluated using a group randomized controlled trial. NEAT Girls is a 12-month multi-component school-based intervention developed in reference to Social Cognitive Theory and includes enhanced school sport sessions, interactive seminars, nutrition workshops, lunch-time physical activity (PA) sessions, PA and nutrition handbooks, parent newsletters, pedometers for self monitoring and text messaging for social support. The following variables were assessed at baseline and will be completed again at 12- and 24-months: adiposity, objectively measured PA, muscular fitness, time spent in sedentary behaviors, dietary intake, PA and nutrition social-cognitive mediators, physical self perception and global self-esteem. Statistical analyses will follow intention-to treat principles and hypothesized mediators of PA and nutrition behavior change will be explored. DISCUSSION: NEAT Girls is an innovative intervention targeting low-active girls using evidence-based behavior change strategies and nutrition and PA messages and has the potential to prevent unhealthy weight gain and reduce the decline in physical activity and poor dietary habits associated with low socio-economic status. Few studies have reported the long-term effects of school based obesity prevention programs and the current study has the potential to make an important contribution to the field. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry No: ACTRN12610000330044. PMID- 21029468 TI - The impact of stroke on emotional intelligence. AB - BACKGROUND: Emotional intelligence (EI) is important for personal, social and career success and has been linked to the frontal anterior cingulate, insula and amygdala regions. AIM: To ascertain which stroke lesion sites impair emotional intelligence and relation to current frontal assessment measurements. METHODS: One hundred consecutive, non aphasic, independently functioning patients post stroke were evaluated with the Bar-On emotional intelligence test, "known as the Emotional Quotient Inventory (EQ-i)" and frontal tests that included the Wisconsin Card Sorting Test (WCST) and Frontal Systems Behavioral Inventory (FRSBE) for correlational validity. The results of a screening, bedside frontal network syndrome test (FNS) and NIHSS to document neurological deficit were also recorded. Lesion location was determined by the Cerefy digital, coxial brain atlas. RESULTS: After exclusions (n = 8), patients tested (n = 92, mean age 50.1, CI: 52.9, 47.3 years) revealed that EQ-i scores were correlated (negatively) with all FRSBE T sub-scores (apathy, disinhibition, executive, total), with self reported scores correlating better than family reported scores. Regression analysis revealed age and FRSBE total scores as the most influential variables. The WCST error percentage T score did not correlate with the EQ-i scores. Based on ANOVA, there were significant differences among the lesion sites with the lowest mean EQ-i scores associated with temporal (71.5) and frontal (87.3) lesions followed by subtentorial (91.7), subcortical gray (92.6) and white (95.2) matter, and the highest scores associated with parieto-occipital lesions (113.1). CONCLUSIONS: 1) Stroke impairs EI and is associated with apathy, disinhibition and executive functioning. 2) EI is associated with frontal, temporal, subcortical and subtentorial stroke syndromes. PMID- 21029469 TI - Reduction of diabetes risk in routine clinical practice: are physical activity and nutrition interventions feasible and are the outcomes from reference trials replicable? A systematic review and meta-analysis. AB - BACKGROUND: The clinical effectiveness of intensive lifestyle interventions in preventing or delaying diabetes in people at high risk has been established from randomised trials of structured, intensive interventions conducted in several countries over the past two decades. The challenge is to translate them into routine clinical settings. The objective of this review is to determine whether lifestyle interventions delivered to high-risk adult patients in routine clinical care settings are feasible and effective in achieving reductions in risk factors for diabetes. METHODS: DATA SOURCES: MEDLINE (PubMed), EMBASE, CINAHL, The Cochrane Library, Google Scholar, and grey literature were searched for English language articles published from January 1990 to August 2009. The reference lists of all articles collected were checked to ensure that no relevant suitable studies were missed. STUDY SELECTION: We included RCTs, before/after evaluations, cohort studies with or without a control group and interrupted time series analyses of lifestyle interventions with the stated aim of diabetes risk reduction or diabetes prevention, conducted in routine clinical settings and delivered by healthcare providers such as family physicians, practice nurses, allied health personnel, or other healthcare staff associated with a health service. Outcomes of interest were weight loss, reduction in waist circumference, improvement of impaired fasting glucose or oral glucose tolerance test (OGTT) results, improvements in fat and fibre intakes, increased level of engagement in physical activity and reduction in diabetes incidence. RESULTS: Twelve from 41 potentially relevant studies were included in the review. Four studies were suitable for meta-analysis. A significant positive effect of the interventions on weight was reported by all study types. The meta-analysis showed that lifestyle interventions achieved weight and waist circumference reductions after one year. However, no clear effects on biochemical or clinical parameters were observed, possibly due to short follow-up periods or lack of power of the studies meta analysed. Changes in dietary parameters or physical activity were generally not reported. Most studies assessing feasibility were supportive of implementation of lifestyle interventions in routine clinical care. CONCLUSION: Lifestyle interventions for patients at high risk of diabetes, delivered by a variety of healthcare providers in routine clinical settings, are feasible but appear to be of limited clinical benefit one year after intervention. Despite convincing evidence from structured intensive trials, this systematic review showed that translation into routine practice has less effect on diabetes risk reduction. PMID- 21029470 TI - Fibrinogen and associated risk factors in a high-risk population: urban Indigenous Australians, the DRUID Study. AB - BACKGROUND: Epidemiological evidence suggests that fibrinogen and CRP are associated with coronary heart disease risk. High CRP in Indigenous Australians has been reported in previous studies including our 'Diabetes and Related diseases in Urban Indigenous population in Darwin region' (DRUID) Study. We studied levels of fibrinogen and its cross-sectional relationship with traditional and non-traditional cardiovascular risk factors in an urban Indigenous Australian cohort. METHODS: Fibrinogen data were available from 287 males and 628 females (aged >= 15 years) from the DRUID study. Analysis was performed for associations with the following risk factors: diabetes, HbA1c, age, BMI, waist circumference, waist-hip ratio, total cholesterol, triglyceride, HDL cholesterol, C-reactive protein, homocysteine, blood pressure, heart rate, urine ACR, smoking status, alcohol abstinence. RESULTS: Fibrinogen generally increased with age in both genders; levels by age group were higher than those previously reported in other populations, including Native Americans. Fibrinogen was higher in those with than without diabetes (4.24 vs 3.56 g/L, p < 0.001). After adjusting for age and sex, the following were significantly associated with fibrinogen: BMI, waist, waist-hip ratio, systolic blood pressure, heart rate, fasting triglycerides, HDL cholesterol, HbA1c, CRP, ACR and alcohol abstinence. On multivariate regression (age and sex-adjusted) CRP and HbA1c were significant independent predictors of fibrinogen, explaining 27% of its variance; CRP alone explained 25% of fibrinogen variance. On factor analysis, both CRP and fibrinogen clustered with obesity in women (this factor explained 20% of variance); but in men, CRP clustered with obesity (factor explained 18% of variance) whilst fibrinogen clustered with HbA1c and urine ACR (factor explained 13% of variance). CONCLUSIONS: Fibrinogen is associated with traditional and non-traditional cardiovascular risk factors in this urban Indigenous cohort and may be a useful biomarker of CVD in this high-risk population. The apparent different associations of fibrinogen with cardiovascular disease risk markers in men and women should be explored further. PMID- 21029471 TI - Executive functions and selective attention are favored in middle-aged healthy women carriers of the Val/Val genotype of the catechol-o-methyltransferase gene: a behavioral genetic study. AB - BACKGROUND: Cognitive deficits such as poor memory, the inability to concentrate, deficits in abstract reasoning, attention and set-shifting flexibility have been reported in middle-aged women. It has been suggested that cognitive decline may be due to several factors which include hormonal changes, individual differences, normal processes of aging and age-related changes in dopaminergic neurotransmission. Catechol-O-methyltransferase (COMT), a common functional polymorphism, has been related to executive performance in young healthy volunteers, old subjects and schizophrenia patients. The effect of this polymorphism on cognitive function in middle-aged healthy women is not well known. The aim of the current study was to investigate whether measures of executive function, sustained attention, selective attention and verbal fluency would be different depending on the COMT genotype and task demand. METHOD: We genotyped 74 middle-aged healthy women (48 to 65 years old) for the COMT Val158Met polymorphism. We analyzed the effects of this polymorphism on executive functions (Wisconsin Card Sorting Test), selective attention (Stroop test), sustained attention (Continuous Performance Test) and word generation (Verbal Fluency test), which are cognitive functions that involve the frontal lobe. RESULTS: There were 27 women with the Val/Val COMT genotype, 15 with the Met/Met genotype, and 32 with the Val/Met genotype. Women carriers of the Val/Val genotype performed better in executive functions, as indicated by a lower number of errors committed in comparison with the Met/Met or Val/Met groups. The correct responses on selective attention were higher in the Val/Val group, and the number of errors committed was higher in the Met/Met group during the incongruence trial in comparison with the Val/Val group. Performance on sustained attention and the number of words generated did not show significant differences between the three genotypes. CONCLUSION: These findings indicate that middle-aged women carriers of the Val158 allele, associated with high-activity COMT, showed significant advantage over Met allele in executive processes and cognitive flexibility. These results may help to explain, at least in part, individual differences in cognitive decline in middle-aged women with dopamine-related genes. PMID- 21029473 TI - Enterobacter nimipressuralis as a cause of pseudobacteremia. AB - BACKGROUND: The clinical significance of the Enterobacter nimipressuralis as human pathogens remains unclear. CASE PRESENTATIONS: The microbiologic culture monitoring system of sterile body fluids revealed on an episode of Enterobacter cloacae and Enterobacter amnigenus in blood culture results on the same day; the antibiotic sensitivity and MIC were nearly the same for both species. First patient was a healthy woman with postmenopausal syndrome, while second patient with herpes zoster. Both patients had febrile sensations without signs of bacteremia. E. amnigenus was also cultured from the unused package of salined cotton in the container through epidemiologic investigation. The cultured Enterobacter species were all identified as E. nimipressuralis through hsp60 gene sequencing and infrequent-restriction-site PCR (IRS-PCR). CONCLUSION: When an unusual microorganisms such as E. nimipressuralis is isolated from blood of a patient with no clinical signs of sepsis, a pseudobacteremia should be suspected. When the antibiogram and MIC test results of bacterial cultures from two or more patients are nearly the same, although the species involved may appear different, it may be necessary to prove that they are the same species through molecular methods. The microbiologic cultures monitoring system will probably help to detect pseudobacteremia and other pseudo infections through reliable and fast identification. PMID- 21029472 TI - A study of the TNF/LTA/LTB locus and susceptibility to severe malaria in highland papuan children and adults. AB - BACKGROUND: Severe malaria (SM) syndromes caused by Plasmodium falciparum infection result in major morbidity and mortality each year. However, only a fraction of P. falciparum infections develop into SM, implicating host genetic factors as important determinants of disease outcome. Previous studies indicate that tumour necrosis factor (TNF) and lymphotoxin alpha (LTalpha) may be important for the development of cerebral malaria (CM) and other SM syndromes. METHODS: An extensive analysis was conducted of single nucleotide polymorphisms (SNPs) in the TNF, LTA and LTB genes in highland Papuan children and adults, a population historically unexposed to malaria that has migrated to a malaria endemic region. Generated P-values for SNPs spanning the LTA/TNF/LTB locus were corrected for multiple testing of all the SNPs and haplotype blocks within the region tested through 10,000 permutations. A global P-value of < 0.05 was considered statistically significant. RESULTS: No associations between SNPs in the TNF/LTA/LTB locus and susceptibility to SM in highland Papuan children and adults were found. CONCLUSIONS: These results support the notion that unique selective pressure on the TNF/LTA/LTB locus in different populations has influenced the contribution of the gene products from this region to SM susceptibility. PMID- 21029474 TI - Deletion of 1.8-kb mRNA of Marek's disease virus decreases its replication ability but not oncogenicity. AB - BACKGROUND: The 1.8-kb mRNA was reported as one of the oncogenesis-related genes of Marek's disease virus (MDV). In this study, the bacterial artificial chromosome (BAC) clone of a MDV field strain GX0101 was used as the platform to generate mutant MDV to examine the functional roles of 1.8-kb mRNA. RESULTS: Based on the BAC clone of GX0101, the 1.8-kb mRNA deletion mutant GX0101Delta(A+C) was constructed. The present experiments indicated that GX0101Delta(A+C) retained a low level of oncogenicity, and it showed a decreased replication capacity in vitro and in vivo when compared with its parent virus, GX0101. Further studies in vitro demonstrated that deletion of 1.8-kb mRNA significantly decreased the transcriptional activity of the bi-directional promoter between 1.8-kb mRNA and pp38 genes of MDV. CONCLUSION: These results suggested that the 1.8-kb mRNA did not directly influence the oncogenesis but related to the replication ability of MDV. PMID- 21029475 TI - Comparison of cardiovascular risk factors between Sri Lankans living in Kandy and Oslo. AB - BACKGROUND: South Asians living in western countries are known to have unfavourable cardiovascular risk profiles. Studies indicate migrants are worse off when compared to those living in country of origin. The purpose of this study was to compare selected cardiovascular risk factors between migrant Sri Lankans living in Oslo, Norway and Urban dwellers from Kandy, Sri Lanka. METHODS: Data on non fasting serum lipids, blood pressure, anthropometrics and socio demographics of Sri Lankan Tamils from two almost similar population based cross sectional studies in Oslo, Norway between 2000 and 2002 (1145 participants) and Kandy, Sri Lanka in 2005 (233 participants) were compared. Combined data were analyzed using linear regression analyses. RESULTS: Men and women in Oslo had higher HDL cholesterol. Men and women from Kandy had higher Total/HDL cholesterol ratios. Mean waist circumference and body mass index was higher in Oslo. Smoking among men was low (19.2% Oslo, 13.1% Kandy, P = 0.16). None of the women smoked. Mean systolic and diastolic blood pressure was significantly higher in Kandy than in Oslo. CONCLUSIONS: Our comparison showed unexpected differences in risk factors between Sri Lankan migrants living in Oslo and those living in Kandy Sri Lanka. Sri Lankans in Oslo had favorable lipid profiles and blood pressure levels despite being more obese. PMID- 21029476 TI - Anti-bacterial activity of intermittent preventive treatment of malaria in pregnancy: comparative in vitro study of sulphadoxine-pyrimethamine, mefloquine, and azithromycin. AB - BACKGROUND: Intermittent preventive treatment of malaria with sulphadoxine pyrimethamine (SP) is recommended for the prevention of malaria in pregnancy in sub-Saharan Africa. Increasing drug resistance necessitates the urgent evaluation of alternative drugs. Currently, the most promising candidates in clinical development are mefloquine and azithromycin. Besides the anti-malarial activity, SP is also a potent antibiotic and incurs significant anti-microbial activity when given as IPTp - though systematic clinical evaluation of this action is still lacking. METHODS: In this study, the intrinsic anti-bacterial activity of mefloquine and azithromycin was assessed in comparison to sulphadoxine pyrimethamine against bacterial pathogens with clinical importance in pregnancy in a standard microdilution assay. RESULTS: SP was highly active against Staphylococcus aureus and Streptococcus pneumoniae. All tested Gram-positive bacteria, except Enterococcus faecalis, were sensitive to azithromycin. Additionally, azithromycin was active against Neisseria gonorrhoeae. Mefloquine showed good activity against pneumococci but lower in vitro action against all other tested pathogens. CONCLUSION: These data indicate important differences in the spectrum of anti-bacterial activity for the evaluated anti-malarial drugs. Given the large scale use of IPTp in Africa, the need for prospective clinical trials evaluating the impact of antibiotic activity of anti-malarials on maternal and foetal health and on the risk of promoting specific drug resistance of bacterial pathogens is discussed. PMID- 21029477 TI - The effect of repeated washing of long-lasting insecticide-treated nets (LLINs) on the feeding success and survival rates of Anopheles gambiae. AB - BACKGROUND: Insecticide-treated nets protect users from mosquito bites, thereby preventing transmissions of mosquito borne pathogens. Repeated washing of nets removes insecticide on the netting rendering them ineffective within a short period. Long-lasting insecticide-treated nets (LLINs) offer longer time protection against such bites because they are more wash resistant, and are preferred to conventionally treated nets. However, there is limited information on the effect of repeated washing of LLINs on the feeding success and survival of wild malaria vectors. METHODS: The current study evaluated the effect of repeated washing of four brands of LLINs on the feeding success and survival rates of Anopheles gambiae sl reared from wild strains. In this study, two- to five-day old F1s, reared from gravid mosquitoes collected from an area with a high coverage of LLINs were offered blood meals through protective barriers of the above LLINs. Mosquitoes were exposed for a period of 10 minutes each time. Nets were tested unwashed and subsequently after every 5th through wash 15. After exposure mosquitoes were sorted out according to their feeding status. They were then held under normal laboratory conditions for 24 hours and mortality was scored in both fed and unfed. RESULTS: It was observed that mosquitoes did not feed through a barrier of unwashed LLINs. However, the feeding success and survival rates increased with successive number of washes and were also net brand dependant. After 15 washes, 49% of vectors succeeded to feed through a protective barrier of PermaNet 2.0 and 50% of the fed died after 24 hrs while after the same number of washes 60% of vectors succeeded to feed through Olyset brand of LLINs and all of them survived. In general, more mosquitoes survived after feeding through Olyset compared to the other four brands that were evaluated. When efficacy of individual LLINs was compared by a t-test analysis to a conventionally treated net, the results were not significantly different statistically for Olyset (p = 0.239) and NetProtect (TNT) (p = 0.135). However, the results were highly significant when comparison was made with PermaNet and Interceptor (BASF); p values 0.015 and 0.025 respectively. CONCLUSION: The result of this study shows that repeated washing of LLINs at short time intervals using local washing methods may render them infective within a short time in preventing local vectors from feeding. PMID- 21029478 TI - Entomologic and molecular investigation into Plasmodium vivax transmission in Singapore, 2009. AB - BACKGROUND: Singapore has been certified malaria free since November 1982 by the World Health Organization and despite occasional local transmission, the country has maintained the standing. In 2009, three clusters of malaria cases were reported in Singapore. METHODS: Epidemiological, entomological and molecular studies were carried out to investigate the three clusters, namely Mandai-Sungei Kadut, Jurong Island and Sembawang. RESULTS: A total of 29 malaria patients, with no recent travel history, were reported in the three clusters. Molecular analysis based on the msp3alpha and msp1 genes showed two independent local transmissions: one in Mandai-Sungei Kadut and another in Sembawang. Almost all cases within each cluster were epidemiologically linked. In Jurong Island cluster, epidemiological link remains uncertain, as almost all cases had a unique genetic profile. Only two cases shared a common profile and were found to be linked to the Mandai Sungei Kadut cluster. Entomological investigation found Anopheles sinensis to be the predominant Anopheline in the two areas where local transmission of P. vivax was confirmed. Anopheles sinensis was found to be attracted to human bait and bites as early as 19:45 hrs. However, all Anopheles mosquitoes caught were negative for sporozoites and oocysts by dissection. CONCLUSION: Investigation of P. vivax cases from the three cluster areas confirmed the occurrence of local transmission in two areas. Although An. sinensis was the predominant Anopheline found in areas with confirmed transmission, the vector/s responsible for the outbreaks still remains cryptic. PMID- 21029480 TI - Long-term survival of a woman with well differentiated papillary mesothelioma of the peritoneum: a case report and review of the literature. AB - INTRODUCTION: Well-differentiated papillary mesothelioma of the peritoneum (WDPMP) is a rare subtype of epitheloid mesothelioma, which is usually seen in young women. WDPMP is generally considered of low malignant potential, however the long-term nature of the tumor remains poorly defined. CASE PRESENTATION: We describe the long-term follow-up of a 60-year-old woman of West African descent who has survived 24 years with WDPMP after receiving extensive local and systemic adjuvant chemotherapy. Her clinical course has included three exploratory laparotomies with intraperitoneal and intravenous chemotherapy over two decades. Her course was complicated by anthracycline-induced cardiomyopathy, for which she underwent an orthotopic heart transplant. Our patient is alive with stable radiological evidence of peritoneal disease, and continues to suffer from chronic abdominal pain. CONCLUSION: No consensus exists regarding optimal treatment strategies for WDPMP. However, given the low malignant potential of the tumor, careful consideration should be made before proceeding with aggressive interventions. Further, long-term follow-up reports are required to fully characterize this tumor. PMID- 21029479 TI - Rhomboid homologs in mycobacteria: insights from phylogeny and genomic analysis. AB - BACKGROUND: Rhomboids are ubiquitous proteins with diverse functions in all life kingdoms, and are emerging as important factors in the biology of some pathogenic apicomplexa and Providencia stuartii. Although prokaryotic genomes contain one rhomboid, actinobacteria can have two or more copies whose sequences have not been analyzed for the presence putative rhomboid catalytic signatures. We report detailed phylogenetic and genomic analyses devoted to prokaryotic rhomboids of an important genus, Mycobacterium. RESULTS: Many mycobacterial genomes contained two phylogenetically distinct active rhomboids orthologous to Rv0110 (rhomboid protease 1) and Rv1337 (rhomboid protease 2) of Mycobacterium tuberculosis H37Rv, which were acquired independently. There was a genome-wide conservation and organization of the orthologs of Rv1337 arranged in proximity with glutamate racemase (mur1), while the orthologs of Rv0110 appeared evolutionary unstable and were lost in Mycobacterium leprae and the Mycobacterium avium complex. The orthologs of Rv0110 clustered with eukaryotic rhomboids and contained eukaryotic motifs, suggesting a possible common lineage. A novel nonsense mutation at the Trp73 codon split the rhomboid of Mycobacterium avium subsp. Paratuberculosis into two hypothetical proteins (MAP2425c and MAP2426c) that are identical to MAV_1554 of Mycobacterium avium. Mycobacterial rhomboids contain putative rhomboid catalytic signatures, with the protease active site stabilized by Phenylalanine. The topology and transmembrane helices of the Rv0110 orthologs were similar to those of eukaryotic secretase rhomboids, while those of Rv1337 orthologs were unique. Transcription assays indicated that both mycobacterial rhomboids are possibly expressed. CONCLUSIONS: Mycobacterial rhomboids are active rhomboid proteases with different evolutionary history. The Rv0110 (rhomboid protease 1) orthologs represent prokaryotic rhomboids whose progenitor may be the ancestors of eukaryotic rhomboids. The Rv1337 (rhomboid protease 2) orthologs appear more stable and are conserved nearly in all mycobacteria, possibly alluding to their importance in mycobacteria. MAP2425c and MAP2426c provide the first evidence for a split homologous rhomboid, contrasting whole orthologs of genetically related species. Although valuable insights to the roles of rhomboids are provided, the data herein only lays a foundation for future investigations for the roles of rhomboids in mycobacteria. PMID- 21029481 TI - The effect of immunomodulators on the immunogenicity of TNF-blocking therapeutic monoclonal antibodies: a review. AB - Therapeutic monoclonal antibodies have revolutionized the treatment of various inflammatory diseases. Immunogenicity against these antibodies has been shown to be clinically important: it is associated with shorter response duration because of diminishing concentrations in the blood and with infusion reactions. Concomitant immunomodulators in the form of methotrexate or azathioprine reduced the immunogenicity of therapeutic antibodies in rheumatoid arthritis, Crohn disease, and juvenile idiopathic arthritis. The occurrence of adverse events does not increase when immunomodulators are added to therapeutic antibodies. The mechanism whereby methotrexate and azathioprine influence immunogenicity remains unclear. Evidence-based consensus on prescribing concomitant immunomodulators is needed. PMID- 21029482 TI - [A woman with vomiting and diarrhea]. AB - A 38-year-old woman was admitted to the emergency department with vomiting, diarrhoea and abdominal pain since four days. She used anticoagulant drugs because of venous thromboembolism. Echography of the abdomen revealed a subcapsular hematoma of the liver. The patient recovered after bloodtransfusion and conservative treatment. PMID- 21029483 TI - [A seatbelt sign following a car accident: look for internal abdominal injury]. AB - We present three patients, a 55-year-old man, a 69-year-old woman and a 25-year old man, with a seatbelt sign following a car accident. All 3 patients exhibited various injuries that may occur in the case of a blunt trauma, for example rib fractures. In one patient, however, symptoms of internal abdominal injury occurred several days after the accident. The presence of a seatbelt sign is associated with an increased risk of internal abdominal injury. We therefore advise a CT scan of the abdomen in patients who present with a seatbelt sign, even if abdominal ultrasound does not reveal signs of injury. PMID- 21029484 TI - [A 73-year-old man with a Merkel cell carcinoma]. AB - A 73-year-old man had a firm node on his right upper arm, which was caused by a Merkel cell carcinoma (MCC). The diagnosis was made on the basis of characteristic histopathological findings and a surgical excision with wide margins followed. Twenty months later a considerable swelling manifested in the right armpit due to a metastasis. During a CT scan of the thorax and abdomen, 2 suspicious abnormalities were seen in the mesenterial adipose tissue of the left lower abdomen and left perirenal adipose tissue. A tissue sample of the last abnormality taken under CT guidance confirmed this to be a metastasis of the MCC. The patient was irradiated but chose not to have chemotherapy. He died 2 years after the diagnosis. Merkel cell carcinoma is a rare and aggressive malignant skin neoplasm. Early recognition facilitates cure of the disease. Treatment is multidisciplinary, but surgery, either alone or in combination with radiotherapy, forms the basis of treating both the localised and regionalized forms of the disease. Chemotherapy may be used in case of disseminated disease and has a reasonable, albeit temporary, effect. The 10-year survival rate varies from 20 70%, dependent on the stage of the disease. PMID- 21029485 TI - [Treatment of hypertension by percutaneous endovascular renal denervation]. PMID- 21029487 TI - [Whole genome sequencing--new opportunities for health care practice?]. AB - In the near future it will probably be possible to unravel the DNA code of the human genome for less than US $ 1,000 by means of 'whole genome sequencing' (WGS). However, its usefulness in clinical practice is questionable. Although WGS of an individual may become relatively inexpensive and easily available, knowledge of the complete DNA sequence in itself does not provide clinically useful information. DNA data need to be analyzed and interpreted, but there are still many gaps and uncertainties in our knowledge of DNA variations and their clinical consequences. WGS may be a useful supplementary testing technique for establishing the diagnosis of monogenic disorders and syndromes, but potentially undesirable or unclear findings may cause ethical and practical problems. Therefore, WGS should only be applied very cautiously and after thorough deliberation of its possible consequences. PMID- 21029488 TI - [Dutch government invests in existing biobanks]. AB - Modern research, aimed at discovering factors that influence health and disease, requires large collections of data and samples. Collaboration between biobanks is therefore essential. The Dutch hub in the network of biobanks, the Biobanking and Biomolecular Resources Research Infrastructure (BBMRI-NL), is one of the major Dutch biobanking initiatives. It is sponsored by the Dutch government through the Netherlands Organization for Scientific Research (NWO). BBMRI-NL sets up collaboration between approximately 150 existing clinical and population biobanks in the Netherlands, and forms the link with the European BBMRI initiative. BBMRI NL aims at enrichment and harmonization of existing Dutch biobanks, at data management and analysis, and at laying the legal, social and ethical foundations, in order to improve access and inter-operability, and to render the information and organization up to date. Other major Dutch initiatives are String of Pearls and LifeLines. Together these will create the conditions needed for Dutch researchers to further develop their strong position in the international biobanking field. PMID- 21029489 TI - [Skin abnormalities as first sign of Waldenstrom macroglobulinaemia]. AB - Small-vessel vasculitis was found in a 56-year-old female patient as the first sign of Waldenstrom macroglobulinemia. After the diagnosis was made by immunological investigation, she was treated successfully by combination therapy with rituximab, cyclophosphamide, vincristine en prednisone. Leukocytoclastic vasculitis occurs in only 5% of patients with Waldenstrom macroglobulinaemia as the first manifestation of this condition. PMID- 21029490 TI - [Diagnosis and treatment of bone metastasis]. AB - The improved prognosis of cancer patients has led to an increased incidence of both bone metastases and (impending) pathological fractures. A solitary bone lesion seen on radiography should never be assumed to be a metastasis. Preoperative biopsy is necessary in patients with a known malignancy and a solitary lytic bone lesion as well as in patients in whom the primary tumor is unknown, in order to prevent an incorrect operation (also known as 'whoops surgery'). If the patient has an (impending) pathological fracture, normal bone healing is not to be expected, not even after stable fixation. Surgical fixation of an impending pathologic fracture is recommended when radiography indicates that a length of more than 3 cm of the cortex of a long bone has been destroyed. If surgical treatment is necessary, it should support the whole long bone in order to enable full weight bearing. When the diagnosis of a bone lesion is uncertain, referral to an experienced treatment centre is recommended. PMID- 21029491 TI - [The national Dutch Institute for Healthcare Improvement guidelines 'Preoperative trajectory': the essentials]. AB - In view of the shortcomings of the organisation of the perioperative process that have been ascertained by the Dutch Health Inspectorate (IGZ), the Inspectorate has requested hospitals and care professionals to implement measures to improve this situation. In response to the IGZ's first report, the Dutch Institute for Healthcare Improvement (CBO) has developed the national, multiprofessional guidelines entitled 'Preoperative Trajectory' which were published in January 2010. Implementation of these guidelines should improve communication between professionals and lead to standardization and transparency of the preoperative patient care process, with uniform handovers and clear responsibilities. These guidelines are the first to provide recommendations at process of care level which are intended to increase patient safety and reduce the risk of damage to patients. PMID- 21029492 TI - [Dutch College of General Practitioners' practice guideline 'Peripheral facial paralysis': a summary]. AB - The practice guideline 'Peripheral facial paralysis' of the Dutch College of General Practitioners provides the general practitioner with guidelines for diagnosis and management of patients with a peripheral facial paralysis. In about two-thirds of cases of peripheral facial paralysis no cause can be found. The diagnosis of this so-called idiopathic peripheral facial paralysis is based on the patient's history and physical examination; additional investigations are not indicated. The natural course is usually good: without treatment 65-85% of patients will regain normal function of the facial muscles. Treatment with corticosteroids is recommended for all patients with an idiopathic peripheral facial paralysis, irrespective of the degree of the paralysis. This increases the chance of complete recovery by approximately 10%. Antiviral treatment is not recommended. PMID- 21029493 TI - [Summary of the practice guideline 'Atrial fibrillation' (first revision) from the Dutch College of General Practitioners]. AB - The revised practice guideline 'Atrial fibrillation' from the Dutch College of General Practitioners provides the general practitioner with guidelines for diagnosis and management of patients with atrial fibrillation. To find patients with atrial fibrillation, it is advised to check cardiac rhythm at every blood pressure measurement. In patients over 65 years old, acceptance of atrial fibrillation with control of ventricular rate is preferred to sinus rhythm normalisation. In therapy with beta-blockers, slow release metoprolol is the drug of choice. An important goal of treatment is the prevention of thrombo-embolic complications. The choice between anticoagulants such as aspirin and coumarin derivatives is based on the CHADS2 score and determined by age (above 75 years) and comorbidity including cardiac failure, diabetes, hypertension, and previous transient ischaemic attack (TIA) or cardiovascular accident (CVA). The adequacy of antithrombotic treatment should be reassessed yearly. PMID- 21029494 TI - [Treatment of children with asthma based on exhaled nitrogen monoxide: added value of nitrogen monoxide measurements has not yet been demonstrated]. AB - There is controversy about the effectiveness of monitoring of asthma treatment based on the fraction of exhaled nitric oxide (FeNO). We performed a systematic review of the literature on the effectiveness of FeNO-guided asthma treatment in children. Up to the end of March 2009, four randomised controlled trials were published, but the results of the trials could not be pooled. Their methodological quality was moderate to high. There was no significant effect of FeNO-guided asthma treatment on the number of symptom-free days, asthma exacerbations, hospital admissions, pulmonary function history (except one trial) and quality of life. There was a moderate effect on prednisone use. Children receiving FeNO-guided treatment used prednisone less often than children whose treatment was based on symptoms. However, children receiving FeNO-guided treatment used higher doses of inhaled corticosteroids. At this moment, FeNO guided asthma treatment cannot be recommended in general practice and paediatric care. PMID- 21029495 TI - [Guideline 'Diagnosis and treatment of inflammatory bowel disease in children']. AB - A multidisciplinary working group has outlined evidence-based practice guidelines for the diagnosis and treatment of inflammatory bowel disease in children (IBD). Both diagnosis and treatment of IBD in children differ significantly from practice in adults. The incidence of IBD in children is low (5.2 per 100,000 per year in the age group 0-17 years), but most of the presenting symptoms are non specific; therefore it is difficult for the general practitioner to recognise the disease in children. For a correct diagnosis, ileocolonoscopy and upper gastrointestinal endoscopy are necessary, often combined with radiological imaging of the small bowel. In children and adolescents with Crohn's disease, nutritional therapy is the first choice of treatment for remission induction. As maintenance treatment, immunomodulators (azathioprine or mercaptopurine) should be started from the time of initial diagnosis. In children and adolescents with ulcerative colitis, the first treatment is with aminosalicylates. Prednisone and/or immunomodulators (azathioprine, cyclosporin) are indicated if there is insufficient response to aminosalicylates. A final treatment option is colectomy. The transition from paediatric to adult health care needs special attention as the patient and his or her parents may be reluctant to change trusted contacts which they have made. PMID- 21029496 TI - [Guideline 'Diagnosis and treatment of inflammatory bowel disease in adults'. I. Diagnosis and treatment]. AB - The Dutch national practice guideline 'Diagnosis and treatment of inflammatory bowel diseases (IBD) in adults' describes the multidisciplinary approach for adult patients with (suspected) IBD, recommended following analysis of the literature according to the principles of evidence based guideline development. The symptoms on first presentation of a patient with IBD are mainly connected with the localisation and severity of the disease and less with the resulting diagnosis 'Crohn's disease' or 'ulcerative colitis'. There is no test by which the diseases can be distinguished with certainty. Clinical course, ileocolonoscopy and histopathological investigation following biopsy form the 'gold standard' for diagnosis of IBD. The final diagnostic step is disease assessment according to the Montreal classification in order to enable unambiguous communication with medical professionals. The first aim of treatment is to treat and stabilise active disease (induction therapy); at the same time maintenance therapy is initiated. A step-up approach is recommended for both treatment aims. Surgical intervention is indicated if the medical treatment is ineffective, in case of intractable gastrointestinal bleeding, in clinically significant gastrointestinal stenosis due to fibrotic scar tissue, or if complications of the inflammation occur such as abscess, peritonitis, or complicated fistula formation. Nutrition and diet do not play a primary therapeutic role in treatment of adult patients with IBD. However, supportive nutritional care is warranted. Probiotics have a demonstrable effect in preventing pouchitis, but not in the treatment of IBD. Alternative medicine has no role to play in the treatment of IBD. The risk of developing colorectal carcinoma is slightly elevated in IBD patients. Therefore, endoscopic surveillance strategies, aimed at early detection of dysplasia, is indicated according to a schedule in which the frequency increases according to the time elapsed since first clinical signs of IBD. PMID- 21029497 TI - [Guideline 'Diagnosis and treatment of inflammatory bowel disease in adults'. II. Special situations and organisation of medical care]. AB - The Dutch national practice guideline 'Diagnosis and treatment of inflammatory bowel diseases (IBD) in adults' describes the multidisciplinary approach for adult patients with (suspected) IBD, recommended following analysis of the literature according to the principles of evidence based guideline development. Ulcerative colitis and Crohn's disease are associated with temporary or permanent extra-intestinal disorders: reactive inflammatory conditions, associated conditions, and those arising as a consequence of long standing, inflammatory, intestinal disease. Treatment is aimed first at the IBD disease process and subsequently at the specific extra-intestinal conditions if complaints persist. The fertility of women with IBD who have not been operated is comparable with those without this complaint. With the exception of methotrexate in both sexes and of sulfasalazine in men, none of the usual medicines for IBD is known to adversely influence fertility. Fertility decreases following abdominal surgery. IBD patients are advised to restrict onset of pregnancy to a longstanding, quiet phase of the disease (ideally > 1 year). The risk of complications during pregnancy is not elevated when IBD is in remission, but is increased during active disease. Nulliparae with an ileoanal pouch have approximately 50% long term risk of developing faecal incontinence; a planned full-term Caesarean section may be beneficial in such cases. Complicated perianal disease is similarly an indication for non-vaginal delivery. The life expectancy for patients with ulcerative colitis is normal, but is slightly lower in patients with Crohn's disease. These positive findings have not yet been incorporated into the practice of life insurance providers. The diversity of IBD patient health care and its delivery by many professionals places stringent requirements on the organisation of care by hospitals and those providing treatment. The transfer process from paediatric specialist to gastroenterologist affects both patients and parents deeply. PMID- 21029498 TI - [Guideline 'Coeliac disease and dermatitis herpetiformis']. AB - The Dutch evidence-based guideline 'Coeliac disease and dermatitis herpetiformis' contains instructions for detection and treatment of coeliac disease. Coeliac disease has a high prevalence: 0.5 - 1.3%. The disease has a broad spectrum of symptoms, frequently also outside the gastrointestinal tract. Relatives of patients and persons with autoimmune diseases, microscopic colitis, IgA deficiency and syndromes of Down, Turner and Williams have an increased risk of coeliac disease. Detection is carried out by determination of IgA antibodies to tissue transglutaminase and endomysium. Testing for IgA antibodies to gliadin is only recommended in children younger than 2 years. Absence of HLA-DQ2 and DQ8 indicates that coeliac disease is most unlikely. The diagnosis should be confirmed by small bowel biopsy. Single biopsy following gluten ingestion is sufficient for diagnosis at all ages. After the diagnosis, patients should be referred to a dietician. Additionally, a yearly follow-up by a paediatrician or internal medical specialist with appropriate gastroenterology specialisation is recommended. PMID- 21029499 TI - [Carbapenem resistance in gram-negative bacteria]. AB - Antibiotic resistance poses a serious threat to the successful treatment of hospitalized patients. Micro-organisms that produce carbapenamases, such as Klebsiella pneumoniae carbapenamases (KPCs) represent the next step in the continuously emerging problem of antibiotic resistance. Restrictions on antibiotic use plus optimal adherence to infection control measures will be crucial to limit the spread of KPC in hospitals in the Netherlands in the coming years. PMID- 21029500 TI - [Coeliac disease: emancipation of a childhood disease]. AB - Our understanding of the pathophysiology and clinical aspects of coeliac disease has improved significantly in the last decades and simultaneously the prevalence of the disease has increased enormously, therefore, the new Dutch practice guideline on coeliac disease and dermatitis herpetiformis is very welcome, because it informs the medical society regarding the new scientific insights and provides helpful tools for clinical practice. However, a few remarks are warrantable. For example: the prevalence rates for coeliac disease of 0.5 to 1.3% of the total Dutch population are disputable and the definition of 'clinical suspicion of coeliac disease' calls for clarification. Furthermore, with regard to the follow-up of patients: who does what, and how often is still to be defined. PMID- 21029501 TI - The professional voice. AB - The human voice is not only the key to human communication but also serves as the primary musical instrument. Many professions rely on the voice, but the most noticeable and visible are singers. Care of the performing voice requires a thorough understanding of the interaction between the anatomy and physiology of voice production, along with an awareness of the interrelationships between vocalisation, acoustic science and non-vocal components of performance. This review gives an overview of the care and prevention of professional voice disorders by describing the unique and integrated anatomy and physiology of singing, the roles of development and training, and the importance of the voice care team. PMID- 21029502 TI - Isolated itching of external auditory canal: clinicopathological study with immunohistochemical determination of antimicrobial peptides. AB - OBJECTIVE: This study aimed to demonstrate the histological and immunohistological features of skin biopsy specimens from patients complaining of isolated itching of the external auditory canal. MATERIALS AND METHODS: A prospective, case-control study was performed of 24 patients undergoing evaluation for contact dermatitis of the external auditory canal, and 24 controls. Skin biopsies were examined histologically by a single, blinded dermatopathologist, using light microscopy, to determine histopathological characteristics. The immunohistological presence of the antimicrobial peptides human beta-defensin-3 and LL-37 cathelicidin was also assessed. Findings for patients and controls were compared. RESULTS: There was a statistically significant difference in the degree of inflammation, comparing patients and controls (p < 0.05). There was no significant difference in the presence of spongiotic changes, comparing patients and controls (p > 0.05). Furthermore, the patients' skin biopsies did not show pronounced expression of human beta-defensin 3 or LL-37 cathelicidin. CONCLUSION: Histological and immunohistological examination of skin biopsies from cases of isolated itching of the external auditory canal did not support a diagnosis of dermatitis. PMID- 21029503 TI - Persistent otorrhoea with an abnormal tympanic membrane secondary to squamous cell carcinoma of the tympanic membrane. AB - OBJECTIVE: The authors present an extremely rare case of carcinoma of the tympanic membrane. METHOD: A case report and review of the literature concerning carcinoma of the tympanic membrane and temporal bone are presented and discussed. RESULTS: The authors present a patient with recurrent otorrhoea and an abnormal tympanic membrane. Biopsy was inconclusive, but resection demonstrated squamous cell carcinoma of the tympanic membrane. We also discuss the investigation, diagnosis, natural history and management of this rare condition, as well as the staging and management of tumours of the temporal bone and the differences between these closely related but prognostically different entities. CONCLUSION: This rare entity can be managed by primary surgical resection if there is no evidence of metastasis. PMID- 21029504 TI - Learning to liaise and elide comme il faut: evidence from bilingual children. AB - Liaison and elision in French are phonological phenomena that apply across word boundaries. French-speaking children make errors in contexts where liaison/elision typically occurs in adult speech. In this study, we asked if acquisition of French liaison/elision can be explained in a constructivist framework. We tested if children's liaison/elision was sensitive to co-occurrence and meaning. We expected children's use of liaison/elision to correlate with their experience with French (estimated by vocabulary). Thirty-one French speaking children (twenty-five bilingual) between three and five years old produced familiar vowel-initial words, following four words: (1) un, (2) deux, (3) un petit and (4) beaucoup de. The children with smaller French vocabularies produced many vowel-initial words and some consonant-initial chunks. The children with larger French vocabularies produced liaison/elision correctly across several frames while associating a number interpretation with liaised consonants. These results suggest that children use a variety of cues to construct the appropriate use of liaison/elision. PMID- 21029505 TI - Predictors of increasing waist circumference in an Australian population. AB - OBJECTIVE: To identify predictors of increasing waist circumference (WC) over a 5 year period in a contemporary population of Australian adults. DESIGN: Longitudinal national cohort of adults participating in the Australian Diabetes, Obesity and Lifestyle Study (AusDiab). SETTINGS: Australian adults in 2000 and 2005. SUBJECTS: A total of 2521 men and 2726 women aged >=25 years at baseline who participated in AusDiab and provided anthropometric measurements at baseline (1999-2000) and follow-up (2005). RESULTS: A >=5% increase of baseline WC occurred in 27 % of men and 38% of women over the 5-year period. In the multivariate analysis of the total population, there was a higher risk of >=5% gain in baseline WC in women, younger people, people with a lower baseline WC, people who never married compared with married/de facto, current smokers compared with never smokers, people with a poorer diet quality and people with a low energy intake. However, there was no significant association with many expected predictors of waist gain such as physical activity. There were some associations between other lifestyle factors and change of WC by sex, age, level of education and across WC categories, but the associations differed across these groups. CONCLUSIONS: A >=5% increase of baseline WC occurred in a significant proportion of men and women over the 5-year period. Of the behavioural factors, poor diet quality was the key predictor of the >=5% increase of baseline WC in this cohort. The findings highlight the need to understand better the causal role of lifestyle in regard to increasing WC over time. PMID- 21029506 TI - Reduction in sugar-sweetened beverages is not associated with more water or diet drinks. AB - OBJECTIVE: The Dutch Obesity Intervention in Teenagers (DOiT) is a school-based randomised controlled trial that was effective in decreasing the consumption of sugar-sweetened beverages among adolescents. The present study examined, using mediation analysis, whether this decrease in consumption of sugar-sweetened beverages could be explained by an increase in the consumption of water or diet drinks. DESIGN: Participants completed a questionnaire about their beverage consumption at baseline and at 8 months (immediately post-intervention), 12- and 20-month follow-ups. A series of multi-level linear regression analyses were performed to examine water and diet drink consumption as potential mediators of the intervention effect on the consumption of sugar-sweetened beverages. SETTING: Eighteen Dutch secondary schools. SUBJECTS: A total of 747 adolescents (mean age: 12.7 years). RESULTS: In addition to the DoiT intervention effect of a reduction in the consumption of sugar-sweetened beverages at 8 months (-284 ml/d; 95 % CI 420, -148) and 12 months (-260 ml/d; 95 % CI -360, -160), there was also a significant reduction in diet drinks at 8 months (-52 ml/d; 95 % CI -89, -16). There was no significant difference in water consumption at any follow-up. The decrease in sugar-sweetened beverage consumption could not be explained by an increase in water or diet drink consumption at any time point. CONCLUSIONS: Interventions aimed at reducing sugar-sweetened beverage consumption may be effective without changing consumption of other beverages. Reducing sugar sweetened beverages was, however, a main message of the DOiT intervention. It is possible that a concomitant promotion of water may have resulted in a greater increase in water intake and replacement of sugar-sweetened beverages with water. PMID- 21029507 TI - High-dose vitamin C supplement use is associated with self-reported histories of breast cancer and other illnesses in the UK Women's Cohort Study. AB - OBJECTIVE: To determine whether frequent vitamin C supplement use is associated with healthier behaviours, and a history of cancer and other illnesses in UK women. DESIGN: The present cross-sectional analysis examines the odds of taking supplements containing vitamin C as recorded in 4 d food diaries, based on lifestyle characteristics and morbidity history self-reported by questionnaire. SETTING: A large national UK cohort study. SUBJECTS: A total of 12,453 women aged between 37 and 79 years. RESULTS: Women frequently taking supplements containing vitamin C, compared to those who did not, had healthier behaviours, including higher consumption of fruit and vegetables. Frequent high-dose vitamin C users (>=1000 mg) had a higher socio-economic status, visited alternative practitioners more often than family or private doctors, and were more likely to be ex-smokers and to drink little or no alcohol. Women who self-reported having had cancer (OR = 1.33, 95% CI 1.00, 1.76) or specifically breast cancer (OR = 1.70, 95% CI 1.14, 2.55), or reported a family history of cancer (OR = 1.16, 95% CI 0.95, 1.41) or breast cancer (OR = 1.26, 95% CI 1.01, 1.58) had increased odds of being frequent high-dose users after adjusting for sociodemographic and health behaviours. Women with personal or family histories of some cardiovascular or intestinal disorders were more likely to take supplements containing vitamin C, though not necessarily at high doses. CONCLUSIONS: High-dose vitamin C intake by UK women was associated with healthier behaviours and a history of breast cancer, total cancer and other illnesses. Consequences of high-dose vitamin C supplement intake are not clear at the population level. PMID- 21029508 TI - Understanding the nutrition information needs of migrant communities: the needs of African and Pacific Islander communities of Logan, Queensland. AB - OBJECTIVE: The purpose of the present study was to investigate the nutrition information needs of the Pacific Islander and African migrant communities of Logan. DESIGN: The present study was structured as a needs assessment and used qualitative research methods. An integrative review was used to gather and analyse data relating to comparative and normative needs, while semi-structured interviews were undertaken for the felt and expressed needs. SETTING: Logan City, Queensland, Australia. SUBJECTS: African and Pacific Islander migrants and health and social service providers within the Logan region. RESULTS: The study identified the need for more accessible means of information delivery such as visual and face-to-face methods or hands-on demonstrations. The study found that information should be delivered in a staged approach on topics including food safety, Australian foods, healthy eating and diet-disease relationships, according to a migrant's length of residence in Australia. CONCLUSIONS: The present study contributes to our understanding of the nutrition information needs of African and Pacific Islander migrant communities of Logan. These findings will enable the development of more appropriate nutrition information and health services for these Logan communities and other similar communities across Australia. PMID- 21029509 TI - The Mediterranean diet in Spain: adherence trends during the past two decades using the Mediterranean Adequacy Index. AB - OBJECTIVE: The purpose of the present study was to analyse the evolution of the Spanish population's global and regional adherence to the Mediterranean diet (MD) since 1987. DESIGN: A cross-sectional study was conducted analysing food consumption from the Spanish Household Consumption Surveys administered by the Spanish Ministry of Agriculture, Fisheries and Food. SETTING: The Mediterranean Adequacy Index (MAI) was applied to measure the adherence to the MD. The significance of the MAI trend was evaluated using a regression model. SUBJECTS: The sample comprises a household consumption data set, which consisted of 2500 households in 1987 and increased to 6200 in 2005. RESULTS: There was a significant decrease in the MAI (P=0.001) during the past two decades in Spanish households. From 1987 to 1997, MD adherence significantly decreased, but since 1998 it appears to have stabilised. In recent years, the daily household availability of several of the food components of the MD has increased. The MAI was observed to be significantly higher during the entire period in some Mediterranean regions, such as Andalusia, and significantly lower in more inland regions, such as Castile-Leon. CONCLUSIONS: During the past two decades, Spain has experienced a significant downward trend in adherence to the predominant dietary pattern, likely as a result of numerous socio-economic changes. However, a stabilisation and a recent slight recovery have been observed during the past decade. PMID- 21029510 TI - Sociodemographic correlates of obesity among Ghanaian women. AB - OBJECTIVE: To examine the sociodemographic correlates of obesity among Ghanaian women. DESIGN: The 2003 and 2008 Ghana Demographic and Health Survey data sets were used to examine the sociodemographic characteristics and the BMI of women aged 15-49 years using descriptive statistics, bivariate and multivariate analyses. SETTING: Ghana is a West African country which is divided into ten administrative regions. The country is further divided into the northern and southern sectors. The northern sector includes the three northern regions (Northern, Upper East and Upper Westen regions) and the seven remaining regions form the southern sector. SUBJECTS: Women aged 15-49 years whose BMI values were available. RESULTS: The overall prevalence of obesity and overweight increased from 25.5 % in 2003 to 30.5 % in 2008. Obesity varied directly with age from 20 to 44 years. Women with higher education had the highest rate of obesity. Obesity was more common among women from wealthy households compared to women from poor households. CONCLUSIONS: Obesity and overweight were found to be more common among older women, urban women, married women, women with higher education and women from rich households. Adoption of healthy lifestyles and the implementation of policies that promote healthy living can help reduce the prevalence of overweight and obesity. PMID- 21029511 TI - Eating patterns and nutritional characteristics associated with sleep duration. AB - OBJECTIVE: To identify major meal and snack eating patterns, and examine their relationships with sleep duration. DESIGN: The analyses included 27 983 participants in a prospective cohort study of women aged 35 to 74 years in the USA or Puerto Rico. RESULTS: The principal component analysis of eight meal and snack frequency items at different times across the day yielded two major eating patterns: (i) eating during conventional eating hours (defined as times from breakfast to dinner); and (ii) dominance of snacks over meals. Comparing the identified eating patterns among women with varying sleep duration (<5, 5-5.9, 6 6.9, 7-7.9, 8-8.9, 9-9.9 and >=10 h daily), the tendency for eating during conventional eating hours decreased with decreasing sleep duration: adjusted mean score of -0.54 (95% CI -0.68, -0.41) in women sleeping for <5 h daily v. 0.08 (95% CI 0.06, 0.11) among those with 7-7.9 h of sleep daily. The extent of snack dominance over meals increased in women with shorter sleep. Women with long (>=10 h) sleep duration had eating patterns similar to those with short (<6 h) sleep duration. Lower tendency for eating during conventional eating hours and greater snack dominance over meals were also related to higher intakes of fat and sweets for energy and lower intakes of fruits and vegetables. CONCLUSIONS: Disrupted eating patterns and diet of poor nutritional quality may exacerbate the development of obesity and metabolic diseases in habitual short and very long sleepers. PMID- 21029512 TI - Neural mechanisms of antidepressant efficacy of the dopamine receptor agonist pramipexole in treatment of bipolar depression. AB - The D2/D3 receptor agonist pramipexole has clinical efficacy as an antidepressant, but its neural mechanisms are unknown. We used 18FDG-PET to investigate the cerebral metabolic effects of pramipexole augmentation of mood stabilizers in bipolar II depression. Fifteen bipolar II depressed patients on mood stabilizers were imaged at baseline and following 6 wk of pramipexole (n=7) or placebo (n=8) augmentation. Relative to placebo, pramipexole treatment was associated with reductions in normalized metabolism in bilateral orbitofrontal cortex, left ventrolateral prefrontal cortex (PFC), and right anteromedial PFC. Voxel-wise analyses additionally showed decreased normalized metabolism in the left inferior parietal cortex and medial frontopolar cortical (BA 10P) area of the anteromedial PFC following pramipexole treatment. These pramipexole-induced effects on regional metabolism suggest a mechanism of antidepressant action distinct from that previously reported under serotonin reuptake inhibitor treatment and appear compatible with evidence that the central dopaminergic system plays a role in the pathophysiology of bipolar depression. PMID- 21029514 TI - Functional heterogeneity of nociceptin/orphanin FQ receptors revealed by (+)-5a Compound and Ro 64-6198 in rat periaqueductal grey slices. AB - The nociceptin/orphanin FQ (N/OFQ) peptide (NOP) receptor is a non-opioid branch of the opioid receptor family implicated in several neurological and psychological disorders, such as pain, anxiety, depression, involuntary movement, addiction, seizure and dementia. Heterogeneity of NOP receptors has been proposed based on the findings of splicing variants and from binding and functional studies. We have previously reported that Ro 64-6198, a NOP receptor agonist, activated a subset, but not all, of N/OFQ-sensitive NOP receptors in midbrain ventrolateral periaqueductal grey (vlPAG). In this study, we found that a new NOP receptor ligand, (+)-5a Compound ((3aS, 6aR)-1-(cis-4-isopropylcyclohexyl)-5' methyl-2'-phenylhexahydrospiro[piperidine-4,1'-pyrrolo[3, 4-c]pyrrole]), also activated a subset of NOP receptors in vlPAG neurons. (+)-5a Compound (0.1-30 MUm) concentration-dependently activated G-protein-coupled inwardly-rectifying potassium (GIRK) channels mediated through the NOP receptors in about 35% of the recorded vlPAG neurons. (+)-5a Compound (EC50: 605 nm) was less potent (1/12) and efficacious (47%) than N/OFQ. In (+)-5a Compound-insensitive neurons, Ro 64-6198 was also ineffective, and vice versa, but N/OFQ activated GIRK channels through NOP receptors. In (+)-5a Compound-sensitive neurons, (+)-5a Compound precluded the effect of Ro 64-6198. Immunofluorecent and morphometric studies showed that most of the (+)-5a Compound-sensitive neurons were multipolar with intensive dendritic arborization and immunoreactive to glutamic acid decarboxylase-67. It is suggested that (+)-5a Compound activates a subset of NOP receptors, similar to the Ro 64-6198-sensitive subset, in the vlPAG neurons which are mostly GABAergic. These results further support the presence of functional heterogeneity of NOP receptors in the midbrain PAG. PMID- 21029513 TI - Brain beta2*-nicotinic acetylcholine receptor occupancy after use of a nicotine inhaler. AB - The Nicotrol(r) (Pfizer, USA) nicotine inhaler reduces craving by mimicking the behavioural component of cigarettes and delivering controlled doses of nicotine, which binds to the beta-2 subunit-containing nicotinic acetylcholine receptors (beta2*-nAChRs). Previous studies examined beta2*-nAChR occupancy after administration of regular and low-nicotine cigarettes. Here, we measured occupancy of beta2*-nAChRs after administration of nicotine via inhaler, and the relationship between occupancy and changes in craving for tobacco smoking and withdrawal symptoms. Tobacco smokers participated in [123I]5-IA-85380 SPECT studies with either a nicotine inhaler (n=9) or tobacco cigarette (n=4) challenge. [123I]5-IA was administered as a bolus plus constant infusion. After equilibrium was achieved, three 30-min baseline scans were collected, and subjects either used the nicotine inhaler or a regular cigarette, and up to six additional scans were obtained. Receptor occupancy was determined based on the Lassen plot method. Craving for tobacco smoking and withdrawal symptoms were evaluated pre- and post-challenge. Use of the nicotine inhaler produced an average 55.9+/-6.4% occupancy of beta2*-nAChRs 2-5 h post-challenge, whereas use of a cigarette produced significantly higher receptor occupancy (F=10.6, p=0.009) with an average 67.6+/-14.1% occupancy 1.5-5 h post-challenge. There was a significant decrease in withdrawal symptoms post-nicotine inhaler use (F=6.13, p=0.04). These results demonstrate significant differences in occupancy of beta2* nAChRs by nicotine after use of the inhaler vs. a cigarette and confirm the ability of the nicotine inhaler to relieve withdrawal symptoms. PMID- 21029515 TI - Duration of immunity induced by companion animal vaccines. AB - Concerns about possible adverse effects from annual vaccination have prompted the reanalysis of vaccine protocols for cats and dogs. In the last decade, several veterinary advisory groups have published protocols that recommend extended revaccination intervals for certain 'core' vaccines. In addition, practicing veterinarians have been asked to consider vaccination as an individualized medical procedure, based on an analysis of risks and benefits for each vaccine in an individual animal. The calls for extended revaccination intervals prompted considerable debate in USA and internationally. Areas of concern include the amount of evidence to support prolonged immunity from various vaccines, the risk of poor responses in individual animals and the possible effects on population immunity. This review examines how the duration of immunity (DOI) to a vaccine is established in animals and humans. It reviews factors that can affect the DOI in an individual animal, including the types of immune defenses stimulated by the pathogen, and the vaccine, host factors such as age and the level of exposure to the pathogen. In addition, it examines DOI studies that were published for canine and feline core vaccines. PMID- 21029516 TI - Evaluation of the properties of silk fibroin films from the non-mulberry silkworm Samia cynthia ricini for biomaterial design. AB - Silk fibroin from a domesticated mulberry silkworm, Bombyx mori, is the most widely used in biomaterial design. We report for the first time the preparation of a relatively smooth (granule free) film of the nonmulberry Samia cynthia ricini fibroin for comparative evaluation of its cell-supporting properties against those of the B. mori fibroin film. The granule formation on the S. c. ricini fibroin film was successfully prevented by facilitating proper rearrangement of the protein molecules, as monitored by FT-IR, by dialysis through a stepwise decrease in the urea concentration in the dialysis media. The lower contact angle of the S. c. ricini fibroin film, compared to the B. mori fibroin film, corresponds well to its lower hydrophobic/hydrophilic amino-acid ratio and grand average of hydropathicity (GRAVY). L929 murine fibroblast cells on the granule-free S. c. ricini fibroin films exhibited greater proliferation and spreading rates than those on the B. mori fibroin films, possibly attributable to its higher content of hydrophilic and positively charged amino acids. It further suggests that fabrication, modification and/or engineering of S. c. ricini fibroin may provide a better biomaterial scaffold design than the more commonly used B. mori fibroin. PMID- 21029517 TI - A novel GAP460 biopolymer for use as a carrier in drug-delivery applications. AB - We synthesized a new non-toxic biopolymer (GAP460) containing gamma,L-glutamic acid and aspartate (Asp). Conjugates of GAP460 and cisplatin exhibited a drug carrying capacity of nearly 40%, 3-times higher than gamma-PGA and dramatically decreasing the amount of biopolymer required for high-dose delivery. Treatment with GAP460-cisplatin conjugate (PACC) not only effectively inhibited tumor growth in nude mice, but also resulted in extended survival and lower nephrotoxicity, suggesting that GAP460 could be used as an effective carrier for drug delivery and that PACC may have potential therapeutic applications in the clinical treatment of cancer. PMID- 21029518 TI - Lipid composition influences the membrane-disrupting activity of antimicrobial methacrylate co-polymers. AB - Amphiphilic methacrylate co-polymers recently demonstrated antimicrobial activity. To understand their activity mechanism, we prepared three homologous methacrylate co-polymers with activity ranging from inactive (MMA) over specifically active (EMA) to non-specifically active (BMA) against bacteria and human erythrocytes. Fluorescent dye leakage assays were used to characterize their membrane-disrupting activity against liposomes of different compositions. From bacterial membrane-mimicking liposomes (composed of Escherichia coli extract or 20:80 DOPG/DOPE), the two active forms, EMA and BMA, caused more dye leakage than the inactive MMA, which mirrors their antibacterial activity trend. From mammalian membrane-mimicking liposomes (composed of DOPC or 20:80 DOPG/DOPC), the highly hemolytic BMA caused significantly more leakage than MMA and EMA, which mirrors its hemolytic activity trend. Moreover, to dissect the effect of intrinsic membrane curvature from that of membrane charge, we used a ternary membrane with constant charge and tunable intrinsic curvature. Specifically, we used membranes composed of DOPG/DOPE/DOPC with constant DOPG content and varying DOPE/DOPC ratio. To significantly disrupt this model, methacrylate co-polymers with different activity profiles required a different minimum threshold DOPE content. In contrast, variation in DOPG/DOPC ratio at constant DOPE concentration did not show a similar influence on the selective membrane-disrupting activity of these co-polymers. Our results suggested that the intrinsic membrane curvature, rather than membrane charge, may play a major role in the selective membrane disrupting activity of methacrylate co-polymers. Since more PE lipids exist in bacterial membranes than in eukaryotic membranes, our results imply that negative intrinsic-curvature lipids such as PE may contribute to the selective antimicrobial activity. PMID- 21029520 TI - International Conference on Emerging Infectious Diseases, 2010. AB - The seventh International Conference on Emerging Infectious Diseases (ICEID) was held in Atlanta, Georgia, USA, July 11-14, 2010. The conference goal was to bring together public health professionals to encourage exchange of scientific and public health information on global emerging infectious disease issues. The conference was organized by the Centers for Disease Control and Prevention (CDC), American Society for Microbiology, the Council of State and Territorial Epidemiologists, the Association of Public Health Laboratories, and the World Health Organization; additional support was provided by 40 other multidisciplinary public health partners. PMID- 21029519 TI - Novel wheat protein films as substrates for tissue engineering. AB - This paper demonstrates that gliadin-free wheat glutenin can be an excellent biomaterial for tissue-engineering applications, better than poly(lactic acid) (PLA). Although plant proteins are more readily available than collagen and silk, limited studies have been conducted on understanding the potential of using plant proteins as biomaterials. Wheat proteins have not been used for tissue engineering due to the cytotoxicity of gliadin. In this research, wheat gluten, glutenin and gliadin were used to develop films and the mechanical properties, water stability and ability of the films to promote the attachment, growth and viability of osteoblast cells was studied in comparison to PLA films. The wheat protein films have good strength ranging from 8 to 30 MPa. Gliadin films experience about 50% weight loss whereas glutenin films have about 90% weight loss after being in water (pH 7.2) for 15 days at 37 degrees C. Gliadin is cytotoxic and the presence of gliadin restricts the cell proliferation on wheat gluten films. However, gliadin-free glutenin films show a higher rate of proliferation of osteoblast cells than the PLA films. Wheat gluten promises to be a potential substrate for tissue engineering and other medical applications. PMID- 21029521 TI - Regulatory oversight and safety of probiotic use. AB - Depending on intended use of a probiotic (drug vs. dietary supplement), regulatory requirements differ greatly. For dietary supplements, premarketing demonstration of safety and efficacy and approval by the Food and Drug Administration are not required; only premarket notification is required. Saccharomyces boulardii is a probiotic regulated as a dietary supplement intended for use by the general healthy population, not as a drug to prevent, treat, or mitigate disease. However, since recent increases in incidence and severity of Clostridium difficile infection, probiotics have been used to treat recurrent and/or refractory disease in hospitalized patients. Saccharomyces fungemia secondary to use of the probiotic has been described for patients who are critically ill, are receiving nutrition enterally, or have a central venous catheter. Before use of a probiotic is considered for hospitalized patients, careful assessment of risk versus benefit must be made. To ensure patient safety, probiotics should be properly handled during administration. PMID- 21029522 TI - Sulfadoxine/pyrimethamine intermittent preventive treatment for malaria during pregnancy. AB - For monitoring efficacy of sulfadoxine/pyrimethamine intermittent preventive treatment for malaria during pregnancy, data obtained from studies of children seemed inadequate. High prevalence of triple and quadruple mutants in the dihydropteroate synthase and dihydrofolate reductase genes of Plasmodium falciparum parasites contrasts with the efficacy of sulfadoxine/pyrimethamine in reducing low birthweights and placental infection rates. In light of this discrepancy, emphasis on using molecular markers for monitoring efficacy of intermittent preventive treatment during pregnancy appears questionable. The World Health Organization recently proposed conducting in vivo studies in pregnant women to evaluate molecular markers for detecting resistance precociously. Other possible alternative strategies are considered. PMID- 21029523 TI - Oropharyngeal cancer epidemic and human papillomavirus. AB - A growing body of research shows that human papillomavirus (HPV) is a common and increasing cause of oropharyngeal squamous cell carcinoma (OSCC). Thus, the International Agency for Research against Cancer has acknowledged HPV as a risk factor for OSCC, in addition to smoking and alcohol consumption. Recently, in Finland, the United Kingdom, the Netherlands, the United States, and Sweden, incidence of OSCC has increased, and an increase in the proportion of HPV positive tumors was noted. On the basis of these data and reports indicating that patients with HPV-positive cancer have their first sexual experience at a young age and have multiple partners, we postulate that increased incidence of OSCC in the United States and some countries in northern Europe is because of a new, primarily sexually transmitted HPV epidemic. We also suggest that individualized treatment modalities and preventive vaccination should be further explored. PMID- 21029524 TI - Salmonella enterica pulsed-field gel electrophoresis clusters, Minnesota, USA, 2001-2007. AB - We determined characteristics of Salmonella enterica pulsed-field gel electrophoresis clusters that predict their being solved (i.e., that result in identification of a confirmed outbreak). Clusters were investigated by the Minnesota Department of Health by using a dynamic iterative model. During 2001 2007, a total of 43 (12.5%) of 344 clusters were solved. Clusters of >=4 isolates were more likely to be solved than clusters of 2 isolates. Clusters in which the first 3 case isolates were received at the Minnesota Department of Health within 7 days were more likely to be solved than were clusters in which the first 3 case isolates were received over a period >14 days. If resources do not permit investigation of all S. enterica pulsed-field gel electrophoresis clusters, investigation of clusters of >=4 cases and clusters in which the first 3 case isolates were received at a public health laboratory within 7 days may improve outbreak investigations. PMID- 21029525 TI - Genetic structure of Plasmodium falciparum and elimination of malaria, Comoros archipelago. AB - The efficacy of malaria control and elimination on islands may depend on the intensity of new parasite inflow. On the Comoros archipelago, where falciparum malaria remains a major public health problem because of spread of drug resistance and insufficient malaria control, recent interventions for malaria elimination were planned on Moheli, 1 of 4 islands in the Comoros archipelago. To assess the relevance of such a local strategy, we performed a population genetics analysis by using multilocus microsatellite and resistance genotyping of Plasmodium falciparum sampled from each island of the archipelago. We found a contrasted population genetic structure explained by geographic isolation, human migration, malaria transmission, and drug selective pressure. Our findings suggest that malaria elimination interventions should be implemented simultaneously on the entire archipelago rather than restricted to 1 island and demonstrate the necessity for specific chemoresistance surveillance on each of the 4 Comorian islands. PMID- 21029526 TI - Effect of vaccination on Bordetella pertussis strains, China. AB - Whole-cell pertussis vaccine was introduced in China in the early 1960s. We used standard typing methods to compare 96 Bordetella pertussis isolates collected before and after introduction of vaccination, during 1953-2005. The following vaccine-type alleles of the pertussis toxin (ptx) gene were characteristic for all prevaccination strains: ptxA2, ptxA3, and ptxA4. The shift to ptxA1 occurred since 1963. All isolates collected since 1983 contained ptxA1. Pertactin (prn) allele 1, prn1, was predominant, although prn2 and prn3 have been detected since 2000. Serotypes fimbriae (Fim) 2 and Fim2,3 were found in all isolates collected before 1986. During 1997-2005, Fim3 became prevalent. Although changes in electrophoresis profiles over time were observed, the predominant profiles during 1997-2005 resembled those during the prevaccine era and those found in Europe before the 1990s. B. pertussis strains in China may differ from those in countries that have a long history of high vaccine coverage. PMID- 21029527 TI - Lymphotropism of Merkel cell polyomavirus infection, Nova Scotia, Canada. AB - To test the hypothesis that Merkel cell polyomavirus (MCPyV) can infect cells of the lymphoid system, we analyzed 353 specimens, including 152 non-Hodgkin lymphomas, 44 Hodgkin lymphomas, 110 benign lymph nodes, 27 lymph nodes with metastasis, and 20 extranodal tissue samples. MCPyV DNA was detected by quantitative PCR in 13 (6.6%) of 196 lymphomas, including 5 (20.8%) of 24 chronic lymphocytic leukemia specimens, and in 11 (10%) of 110 benign lymph nodes, including 8 (13.1%) of 61 samples of reactive hyperplasia and 3 (10.3%) of 29 normal lymph nodes. Other samples were MCPyV negative. Sequence analysis of 9 virus-positive samples confirmed the identity of MCPyV; 3 viral strains were represented. Immunohistochemical testing showed that 1 T-cell lymphoma expressed MCPyV T-antigen. These findings suggest that the lymphoid system plays a role in MCPyV infection and may be a site for MCPyV persistence. PMID- 21029528 TI - Comparison of 3 infrared thermal detection systems and self-report for mass fever screening. AB - Despite limited evidence regarding their utility, infrared thermal detection systems (ITDS) are increasingly being used for mass fever detection. We compared temperature measurements for 3 ITDS (FLIR ThermoVision A20M [FLIR Systems Inc., Boston, MA, USA], OptoTherm Thermoscreen [OptoTherm Thermal Imaging Systems and Infrared Cameras Inc., Sewickley, PA, USA], and Wahl Fever Alert Imager HSI2000S [Wahl Instruments Inc., Asheville, NC, USA]) with oral temperatures (>= 100 degrees F = confirmed fever) and self-reported fever. Of 2,873 patients enrolled, 476 (16.6%) reported a fever, and 64 (2.2%) had a confirmed fever. Self-reported fever had a sensitivity of 75.0%, specificity 84.7%, and positive predictive value 10.1%. At optimal cutoff values for detecting fever, temperature measurements by OptoTherm and FLIR had greater sensitivity (91.0% and 90.0%, respectively) and specificity (86.0% and 80.0%, respectively) than did self reports. Correlations between ITDS and oral temperatures were similar for OptoTherm (rho = 0.43) and FLIR (rho = 0.42) but significantly lower for Wahl (rho = 0.14; p < 0.001). When compared with oral temperatures, 2 systems (OptoTherm and FLIR) were reasonably accurate for detecting fever and predicted fever better than self-reports. PMID- 21029529 TI - Decrease in shigellosis-related deaths without Shigella spp.-specific interventions, Asia. AB - In 1999, a review of the literature for 1966-1997 suggested that ~1.1 million persons die annually of shigellosis, including ~880,000 in Asia. Our recent review of the literature for 1990-2009 indicates that ~125 million shigellosis cases occur annually in Asia, of which ~14,000 are fatal. This estimate for illnesses is similar to the earlier estimate, but the number of deaths is 98% lower; that is, the lower estimate of deaths is associated with markedly reduced case-fatality rates rather than fewer cases. Shigella spp.-related deaths decreased substantially during a period without Shigella spp.-specific interventions. We speculate that nonspecific interventions, e.g., measles vaccination, vitamin A supplementation, and improved nutrition, may have led to the reduced number of shigellosis-related deaths. PMID- 21029530 TI - Measles virus strain diversity, Nigeria and Democratic Republic of the Congo. AB - We investigated the genetic diversity of measles virus (MV) in Nigeria (2004 2005) and the Democratic Republic of the Congo (DRC) (2002-2006). Genotype B3 strains circulating in Kinshasa, DRC, in 2002-2003 were fully replaced by genotype B2 in 2004 at the end of the second Congo war. In Nigeria (2004-2005), two genetic clusters of genotype B3, both of which were most closely related to 1 variant from 1998, were identified. Longitudinal analysis of MV strain diversity in Nigeria suggested that only a few of the previously described 1997-1998 variants had continued to circulate, but this finding was concomitant with a rapid restoration of genetic diversity, probably caused by low vaccination coverage and high birth rates. In contrast, the relatively low genetic diversity of MV in DRC and the genotype replacement in Kinshasa reflect a notable improvement in local measles control. PMID- 21029531 TI - Outbreaks of pandemic (H1N1) 2009 and seasonal influenza A (H3N2) on cruise ship. AB - To determine the extent and pattern of influenza transmission and effectiveness of containment measures, we investigated dual outbreaks of pandemic (H1N1) 2009 and influenza A (H3N2) that had occurred on a cruise ship in May 2009. Of 1,970 passengers and 734 crew members, 82 (3.0%) were infected with pandemic (H1N1) 2009 virus, 98 (3.6%) with influenza A (H3N2) virus, and 2 (0.1%) with both. Among 45 children who visited the ship's childcare center, infection rate for pandemic (H1N1) 2009 was higher than that for influenza A (H3N2) viruses. Disembarked passengers reported a high level of compliance with isolation and quarantine recommendations. We found 4 subsequent cases epidemiologically linked to passengers but no evidence of sustained transmission to the community or passengers on the next cruise. Among this population of generally healthy passengers, children seemed more susceptible to pandemic (H1N1) 2009 than to influenza (H3N2) viruses. Intensive disease control measures successfully contained these outbreaks. PMID- 21029532 TI - Enhanced surveillance of coccidioidomycosis, Arizona, USA, 2007-2008. AB - Coccidioidomycosis is endemic to the southwestern United States; 60% of nationally reported cases occur in Arizona. Although the Council of State and Territorial Epidemiologists case definition for coccidioidomycosis requires laboratory and clinical criteria, Arizona uses only laboratory criteria. To validate this case definition and characterize the effects of coccidioidomycosis in Arizona, we interviewed every tenth case-patient with coccidioidomycosis reported during January 2007-February 2008. Of 493 patients interviewed, 44% visited the emergency department, and 41% were hospitalized. Symptoms lasted a median of 120 days. Persons aware of coccidioidomycosis before seeking healthcare were more likely to receive an earlier diagnosis than those unaware of the disease (p = 0.04) and to request testing for Coccidioides spp. (p = 0.05). These findings warrant greater public and provider education. Ninety-five percent of patients interviewed met the Council of State and Territorial Epidemiologists clinical case definition, validating the Arizona laboratory-based case definition for surveillance in a coccidiodomycosis-endemic area. PMID- 21029533 TI - Experimental pandemic (H1N1) 2009 virus infection of cats. AB - To demonstrate that pandemic (H1N1) 2009 virus may cause respiratory disease in cats, we intratracheally infected cats. Diffuse alveolar damage developed. Seroconversion of sentinel cats indicated cat-to-cat virus transmission. Unlike in cats infected with highly pathogenic avian influenza virus (H5N1), extrarespiratory lesions did not develop in cats infected with pandemic (H1N1) 2009 virus. PMID- 21029534 TI - Reassortment of ancient neuraminidase and recent hemagglutinin in pandemic (H1N1) 2009 virus. AB - Sequence analyses show that the outbreak of pandemic (H1N1) 2009 resulted from the spread of a recently derived hemagglutinin through a population of ancient and more diverse neuraminidase segments. This pattern implies reassortment and suggests that the novel form of hemagglutinin conferred a selective advantage. PMID- 21029535 TI - Prevalence and genetic structures of Streptococcus pneumoniae serotype 6D, South Korea. AB - To determine prevalence and genetic structures of new serotype 6D strains of pneumococci, we examined isolates from diverse clinical specimens in South Korea during 1991-2008. Fourteen serotype 6D strains accounted for 10.4% of serogroup 6 pneumococci from blood, sputum, nasopharynx, and throat samples. Serotype 6D strains consisted of 3 sequence types. PMID- 21029536 TI - Multidrug-resistant Salmonella enterica serovar Infantis, Israel. AB - To determine whether rapid emergence of Salmonella enterica serovar Infantis in Israel resulted from an increase in different biotypes or spread of 1 clone, we characterized 87 serovar Infantis isolates on the genotypic and phenotypic levels. The emerging strain comprised 1 genetic clone with a distinct pulsed field gel electrophoresis profile and a common antimicrobial drug resistance pattern. PMID- 21029537 TI - Extended spectrum beta-lactamase-producing Escherichia coli in neonatal care unit. AB - An outbreak of extended-spectrum beta-lactamase-producing Escherichia coli in a neonatal care unit began with transmission from a mother to her newborn twins during vaginal delivery. Subsequently, infection spread by healthcare worker contact with other neonates; a healthcare worker also was infected. Knowledge about transmission may improve infection control measures. PMID- 21029538 TI - Hepatitis E virus infection in sheltered homeless persons, France. AB - To determine the prevalence of hepatitis E virus (HEV) infection among sheltered homeless persons in Marseille, France, we retrospectively tested 490 such persons. A total of 11.6% had immunoglobulin (Ig) G and 2.5% had IgM against HEV; 1 person had HEV genotype 3f. Injection drug use was associated with IgG against HEV. PMID- 21029540 TI - Genome sequence conservation of Hendra virus isolates during spillover to horses, Australia. AB - Bat-to-horse transmission of Hendra virus has occurred at least 14 times. Although clinical signs in horses have differed, genome sequencing has demonstrated little variation among the isolates. Our sequencing of 5 isolates from recent Hendra virus outbreaks in horses found no correlation between sequences and time or geographic location of outbreaks. PMID- 21029541 TI - Importation of dengue virus type 3 to Japan from Tanzania and Cote d'Ivoire. AB - Travelers can introduce viruses from disease-endemic to non-disease-endemic areas. Serologic and virologic tests confirmed dengue virus infections in 3 travelers returning to Japan: 2 from Tanzania and 1 from Cote d'Ivoire. Phylogenetic analysis of the envelope gene showed that 2 genetically related virus isolates belonged to dengue virus type 3 genotype III. PMID- 21029539 TI - Enterovirus 71 infection with central nervous system involvement, South Korea. AB - We assessed neurologic sequelae associated with an enterovirus 71 (EV71) outbreak in South Korea during 2009. Four of 94 patients had high signal intensities at brainstem or cerebellum on magnetic resonance imaging. Two patients died of cardiopulmonary collapse; 2 had severe neurologic sequelae. Severity and case fatality rates may differ by EV71 genotype or subgenotype. PMID- 21029542 TI - Comparison of survey methods in norovirus outbreak investigation, Oregon, USA, 2009. AB - We compared data from an Internet-based survey and a telephone-based survey during a 2009 norovirus outbreak in Oregon. Survey initiation, timeliness of response, and attack rates were comparable, but participants were less likely to complete Internet questions. Internet-based surveys permit efficient data collection but should be designed to maximize complete responses. PMID- 21029543 TI - Typing of lymphogranuloma venereum Chlamydia trachomatis strains. AB - We analyzed by multilocus sequence typing 77 lymphogranuloma venereum Chlamydia trachomatis strains from men who have sex with men in Europe and the United States. Specimens from an outbreak in 2003 in Europe were monoclonal. In contrast, several strains were in the United States in the 1980s, including a variant from Europe. PMID- 21029544 TI - Enterovirus 75 encephalitis in children, southern India. AB - Recent outbreaks of enterovirus in Southeast Asia emphasize difficulties in diagnosis of this infection. To address this issue, we report 5 (4.7%) children infected with enterovirus 75 among 106 children with acute encephalitis syndrome during 2005-2007 in southern India. Throat swab specimens may be useful for diagnosis of enterovirus 75 infection. PMID- 21029545 TI - Isolation of ancestral sylvatic dengue virus type 1, Malaysia. AB - Ancestral sylvatic dengue virus type 1, which was isolated from a monkey in 1972, was isolated from a patient with dengue fever in Malaysia. The virus is neutralized by serum of patients with endemic DENV-1 infection. Rare isolation of this virus suggests a limited spillover infection from an otherwise restricted sylvatic cycle. PMID- 21029546 TI - Estimates of the true number of cases of pandemic (H1N1) 2009, Beijing, China. AB - During 2009, a total of 10,844 laboratory-confirmed cases of pandemic (H1N1) 2009 were reported in Beijing, People's Republic of China. However, because most cases were not confirmed through laboratory testing, the true number is unknown. Using a multiplier model, we estimated that ~1.46-2.30 million pandemic (H1N1) 2009 infections occurred. PMID- 21029547 TI - Plasmid-mediated quinolone resistance among non-Typhi Salmonella enterica isolates, USA. AB - We determined the prevalence of plasmid-mediated quinolone resistance mechanisms among non-Typhi Salmonella spp. isolated from humans, food animals, and retail meat in the United States in 2007. Six isolates collected from humans harbored aac(6')Ib-cr or a qnr gene. Most prevalent was qnrS1. No animal or retail meat isolates harbored a plasmid-mediated mechanism. PMID- 21029548 TI - Hemolytic-uremic syndrome in a grandmother. PMID- 21029549 TI - Typhoid fever among children, Ghana. PMID- 21029550 TI - Shigella spp. antimicrobial drug resistance, Papua New Guinea, 2000-2009. PMID- 21029551 TI - Fatal avian influenza (H5N1) infection in Human, China. PMID- 21029552 TI - Mycobacterium heckeshornense infection in HIV-infected patient. PMID- 21029553 TI - Geographic expansion of Baylisascaris procyonis roundworms, Florida, USA. PMID- 21029554 TI - Vibrio cholerae O1 variant with reduced susceptibility to ciprofloxacin, Western Africa. PMID- 21029555 TI - Yersinia pestis DNA sequences in late medieval skeletal finds, Bavaria. PMID- 21029556 TI - Two clusters of HIV-1 infection, rural Idaho, USA, 2008. PMID- 21029557 TI - Pandemic (H1N1) 2009 and oseltamivir resistance in hematology/oncology patients. PMID- 21029558 TI - Acute encephalopathy and pandemic (H1N1) 2009. PMID- 21029559 TI - Oseltamivir-resistant pandemic (H1N1) 2009 treated with nebulized zanamivir. PMID- 21029560 TI - Enteric viruses in ready-to-eat packaged leafy greens. PMID- 21029561 TI - The persistence of influenza infection. PMID- 21029563 TI - A moveable feast. AB - A basket of grapes painted by Zeuxis more than 2,000 years ago was so realistic, the grapes so enticing, that birds flew down from the sky to peck at the picture, wrote Pliny the Elder in The Natural History. Food imagery, around since antiquity, expanded and flourished during the 17th century, as part of renewed interest in still-life painting in the Netherlands but also among German, French, Italian, and Spanish artists of the same period. PMID- 21029564 TI - Ultrasound imaging for the rheumatologist XXIX. Sonographic assessment of the knee in patients with osteoarthritis. AB - OBJECTIVES: To investigate the prevalence and severity of sonographic-detected abnormalities in knee osteoarthritis (OA) and to correlate ultrasound (US) findings with clinical data. METHODS: Outpatients with chronic, painful knee OA according to the ACR criteria were consecutively recruited and underwent clinical and US examinations. An expert rheumatologist recorded the presence of knee joint pain, swelling and tenderness, patient's global assessment of knee pain using visual analogue scale (VAS), and Lequesne Index of severity for knee OA. A second rheumatologist, blinded to the clinical data, performed the knee US examination using a Logiq9 machine equipped with a 12MHz linear probe and registering the presence of joint effusion, synovial proliferation, power Doppler (PD) signal, Baker's cyst, osteophytes and femoral cartilage abnormalities. RESULTS: One hundred and sixty-four knees of 82 patients (53 women, 29 men) were studied; mean age was 63.2+/-8.1 SD years, mean disease duration was 4.3+/-5.6 SD years. All patients complained of at least one knee joint pain during physical activity. Mean patient's VAS for knee pain was 48.4+/-19.9 SD mm, mean Lequesne Index was 8.2+/-4.4 SD. Knee swelling was present in 39% of the patients and tenderness was found in 65.8%. US showed: joint effusion in 43.3% of the patients, synovial proliferation in 22.1%, PD signal in 2.9%, Baker's cysts in 6.6%, cartilage abnormalities in 79%, osteophytes in 100%. In all patients US findings were present at least at the level of one knee. Statistically significant correlations were demonstrated between a composite inflammatory score and both VAS (p=0.004) and Lequesne Index (p<0.0001). CONCLUSIONS: This US study showed both inflammatory abnormalities and structural damage lesions in knee OA. Interestingly, statistically significant correlations were demonstrated between US inflammatory findings and the main clinical tests for OA, confirming that sonography has a relevant role in the global evaluation of patients with knee OA. PMID- 21029565 TI - Clinical features and outcome in a Danish cohort of juvenile dermatomyositis patients. AB - OBJECTIVES: To assess disease characteristics and outcome in Danish juvenile dermatomyositis (JDM) patients (1977-2007). METHODS: Medical record review of hospital records identified from the National Patient Register. RESULTS: Fifty seven JDM patients were identified. Follow-up time was 7 years (range 0.06-30). Female:male ratio was 2.5:1. Mean age at disease onset was 7 years (SD+/-3.7), range 1.5-16.0 years. Diagnostic delay was 0.7 years (SD+/-1.6), range 0.04-9 years. Mean disease duration was 3.7 years (SD+/-3.5), range 0.7-9 years. Thirty nine patients (70%) were in full remission. Three patients (5%) were deceased. Disease/treatment-induced damage was present in 35 (61%) patients. Decreased pulmonary function occurred early in the disease course (median 10 months), osteoporosis and calcinosis occurred later (median 18 and 22 months). Four patients developed persistent damage within the first 6 months, four developed calcinosis within the first year. Shorter disease duration was associated with less damage (p=0.004). In a multivariate assessment analysis age >10 years at disease onset was associated with more damage (p<0.01), OR 10.96 (CI 1.6-73.6), and disease duration >4 years was associated with calcinosis (p=0.01) OR 23.2 (CI 2.6-206.2). CONCLUSIONS: We present a nationwide retrospective study of Danish JDM patients from 1977-2007. Although 70% were in remission, 61% of the patients had clinical signs of damage. Only a few patients developed damage within the first year of the disease. Longer disease duration and higher age at disease onset was correlated with more disease damage. PMID- 21029566 TI - Mixed crystal-induced arthropathy--a rare finding. PMID- 21029567 TI - Recurrent pericarditis caused by a rare mutation in the TNFRSF1A gene and with excellent response to anakinra treatment. PMID- 21029568 TI - [Comparison of three series of histological classification for lung cancer]. PMID- 21029569 TI - [Epidemiology and preventive medicine of lung cancer]. PMID- 21029570 TI - [The new theories and techniques in the surgical treatment of lung cancer]. PMID- 21029572 TI - [Combined treatment before and after operation for non-small cell lung cancer]. PMID- 21029571 TI - [Advances in molecular biology of lung cancer]. PMID- 21029573 TI - [Advances in radiotherapy of lung cancer]. PMID- 21029574 TI - [Advances in chemotherapy of lung cancer]. PMID- 21029575 TI - [Transformation of human bronchial epithelial cells BEP2D induced by 238Pu alpha particles]. AB - BACKGROUND: To establish a model for the study of transformation of human cell by radon and its progeny. METHODS: BEP2D, a HPV18 immortalized human bronchial epithelial cell line, was irradiated with high-energy alpha-particles emitted by 238Pu. RESULTS: A single 1. 5 Gy dose of alpha-particles induced transformation of the cells. A series of sequential steps arose among transformed cells, including altered growth kinetics, resistance to serum-induced terminal differentiation, and anchorage-independence growth. CONCLUSIONS: This cell line may provide a model to study the cellular and molecular changes at various stages in radiation carcinogenesis. PMID- 21029576 TI - [Studies on release characteristics and cytotoxicity of 5-fluorouracil loaded polylactide microspheres on lung cancer cell lines]. AB - BACKGROUND: To investigate the release characteristics and cytotoxicity of 5 fluorouracil loaded polylactide microspheres on lung cancer cell lines. METHODS: The release characteristic of 5-FU-PLA microspheres was detected by constant temperature vibration dialysis assay. The antitumor activities of 5-FU-PLA microspheres against human and mouse lung, gastric and hepatocellular carcinoma cell lines were detected byMTT colorimetric assay. RESULTS: 5-FU-PLA microspheres had a good function of extended-release, its t 1/ 2 was 10. 4 days, and the release process had no blow up effect. The lung and gastric cancer cell lines were more sensitive than hepatocellular cancer cell line to 5-FU-PLA microspheres. The antitumor activity significantly correlated with the time of drug action and the dose of 5-FU released from the microspheres. CONCLUSIONS: 5 FU is well distributed in 5-FU-PLA microspheres. Its preparing and releasing processes have no influence on the effect of 5-FU. It can keep the antitumor activities for a relatively long time. The current study provides an experimental basis for interventional therapy of tumors. PMID- 21029577 TI - [Cell cycle arrest and apoptosis induced by arsenic trioxide in human lung cancer cell line]. AB - BACKGROUND: To explore the potential therapeutic effect of arsenic trioxide(As2O3 ) on human lung cancer. METHODS: Cell growth curves, cell proliferation, cell cycle and apoptosis of human lung cancer cell line GLC-82 were detected by theMTT method and flowcytometry (FCM) . RESULTS: The data showed that As2O3 significantly inhibited proliferation of GLC-82 cells and the inhibiting effects had a dose-and time-dependence. The cell proliferation inhibition rate was 81. 05% when treated with 4. 0 Lmol/L As2O3 for 96 hours. The change of DNA content of GLC-82 cells indicated that As2O3 was able to block cell cycle progress in G2/M phase, with appearance of sub-G1 peak in a dose-dependent manner. CONCLUSIONS: As2O3 can effectively inhibit the proliferation of human lung cancer cell line GLC-82 and the possible mechanisms may be related to G2/M phase arrest and apoptosis induced by As2O3. PMID- 21029578 TI - [Establishment and growth characteristics of mouse lung cancer B7 fusion cells]. AB - BACKGROUND: To ameliorate expression B7 molecule of tumor cell. METHODS: Mouse lung cancer cell line ALA9702 and active B lymphocytes were fused by polyethylene glycol. After screening with ELISA and immunocytochemistry, the expression of lung cancer antigen and B7 molecule in the fusion cells were monitored by S-P immunocytochemistry staining. Proliferation of the fusion cells was observed in vitro and in vivo. RESULTS: A fusion cell line, FLB2C, was obtained through screening. FLB2C could express the lung cancer antigen and B7 molecule. The results of in vitro culture showed that the wall adherence characteristic of FLB2C was abated and the growth of FLB2C was slower than that of ALA9702 . The cell multiplication time of FLB2C prolonged and no colony was formed in soft agar. No tumor mass was observed in vivo after inoculation of FLB2C into mice. CONCLUSIONS: Expression of B7 molecule in tumor cell can be ameliorated through cell fusion, thereby antigenicity of tumor cell will be raised. The oncogenicity of FLB2C is obviously weakened through fusion with normal cells. This provides the basis for preparation of better lung cancer vaccines. PMID- 21029579 TI - [Experimental research of tumor infiltrating lymphocytes for treatment of lung cancer]. AB - BACKGROUND: To explore the conditions and characterization of tumor infiltrating lymphocytes(TILs) isolation and expansion. METHODS: TILs were separated from tissue samples which obtained from the surgically removed tumor of 67 patients with lung cancer bymechanic and enzyme digestion and discontinuous density Ficoll paque gradient centrifugation ways. TILs from 34 patients were incubated with 10% human type AB serum RPMI-1640 in vitro. RESULTS: The average number of TIL was 6. 84*106 per gram tumor tissue. The number of TIL from patients in stage I was greater than that from patients in stage III and IV , but with no difference in expanding among them. The number of TIL from patients with adenocarcinoma was similar to that with squamous cell carcinoma, but TIL isolated from adenocarcinoma expanded much more faster than that from squamous cell carcinoma. TIL expanded rapidly during 7-28 days and most of them appeared the maximum expansion within 35 days. TIL incubated from 17 of 34 patients had expanded exceeding 1*109, so the rate of infusion was 50%. CONCLUSIONS: The results suggest TIL can be effectively separated from the tumor and expanded in vitro and these provide the basis for adoptive immunotherapy with TIL in the treatment of lung cancer. PMID- 21029580 TI - [The application of spiral CT angiography in cancerous invasion of central pulmonary artery in lung cancer]. AB - BACKGROUND: To apply spiral CT angiography( SCTA) as imaging method of pulmonary angiography and study the imaging findings of cancerous invasion of central pulmonary artery (CICPA) in lung cancer patients by means of spiral CT pulmonary angiography (SCTPA) . METHODS: Thirty patients with central type of lung cancer proved by bronchoscopy biopsy or surgery underwent SCTPA, and 30 cases who had negative results on conventional CT as control. Technic parameters of SCTPA applied for both groups were as follows: contrast medium injection rate of 3-4ml/ s, collimation of 3mm, pitch of 1. 5, reconstruction interval of 1. 2 mm. The CT manifestations of vessel course and lumen of central pulmonary artery(CPA) were observed and the enhancement intensity of CICPA segment wasmeasured by 3-D imaging of CTA. RESULTS: The changes of vessel course were found in 18 cases( 60%) . The direction of displacement of CPA was different depending on predominant site of the mass and the pathway of CICPA. Centripetal or eccentric stenosis of CPA lumen in various degree with rigid and smooth contour was visualized in 26 cases( 86. 7%) . Decreased enhancement intensity of CPA was significantly shown in cases whose CPA lumen severely narrowed ( P < 0. 05) , and not distinct while stenosis of CPA lumen wasmild tomoderate degree ( P > 0. 05) . CONCLUSIONS: The direct CT signs of CICPA in lung cancer by SCTPA in this study include displacement of vessel course, stenosis of lumen and decreased intensity of contrast enhancement of CPA. SCTPA is a significant complement to conventional CT in diagnosis of CICPA in lung cancer. PMID- 21029581 TI - [Analysis of the relationship between p53 gene mutation and clinical pathophysiological characteristics of primary non-small cell lung cancer]. AB - BACKGROUND: To investigate the significance of p53 gene mutations in non-small cell lung cancer, with focusing on the four highly conserved regions of the p53 gene. METHODS: Point mutations of the p53 gene were detected in 40 lung cancer tissues and 8 benign pulmonary lesions as control by polymerase chain reaction single strand conformation polymorphism ( PCR-SSCP) analysis. RESULTS: Mutations of the p53 gene were found in 19 of 40 lung cancer samples ( 47. 5%) . The frequency of the p53 gene mutations varied among the different stage ( stage I + II vs stage III + IV was 22. 2% vs 68. 2% , P < 0. 005) , and lymph node netastasis status (N1-2 vs N0 was 57. 1% vs 16. 7%, P < 0. 025) of non-small cell lung cancers. CONCLUSIONS: The results suggest that p53 gene mutations may be associated with the carcinogenesis and progression of non-small cell lung cancer. PMID- 21029582 TI - [Relationship between expression of lung resistance protein gene and clinical pathophysiological characteristics of lung cancer]. AB - BACKGROUND: To study the relationship between lung resistance protein gene (LRP) expression and clinical pathophysiological characteristics of lung cancer. METHODS: Expression of LRP gene was determined in 49 lung cancer samples and 41 corresponding paracancerous tissues by RT-PCR. RESULTS: LRP was expressed in lung cancers and corresponding paracancerous tissues. The positive expression rate was 63. 3%( 31/ 49) in cancer tissues and 21. 9% ( 9/ 41) in corresponding paracancerous tissues respectively ( P< 0. 01) . The positive rate in NSCLC ( 29/ 41, 70. 7%)was significantly higher than that in SCLC ( 2/ 8, 25%) ( P < 0. 05) , and the positive rate in adenocarcinoma ( 11/ 12, 91. 7%) was also remarkably higher than that in squamous cell carcinoma ( 11/ 22, 50%) ( P < 0. 05) . In addition, LRP expression in the smokers ( 26/ 35, 74. 3%) was significantly higher than that in the non-smokers ( 5/ 14, 35. 7%) ( P< 0. 05) . CONCLUSIONS: The expression of LRP may be related to drug resistance of lung cancer, and smoking may increase LRP gene expression. PMID- 21029583 TI - [Killing effect of low intensity ultrasound on human lung cancer cells in vitro]. AB - BACKGROUND: To investigate the effects of low intensity ultrasound on human lung cancer cells. METHODS: The human small cell lung cancer cells line SM, adenocarcinoma cell line A2 and human lung fibroblast cells FB were treated with low intensity ultrasound, and the killing effects of ultrasound on the cells were detected by the trypan blue exclusion and clonogenic survival assay. RESULTS: The killing effects of low intensity ultrasound ( 0. 8W/ cm2) on various type of human lung cancer and human pulmonary fibroblast were observed after 3-minute treatment. All of the cells were killed by sonicate for 10-minute treatment. The higher the cell concentration, the lower the killing efficiency. The temperature in the tube containing cell suspension did not obviously increase after 10-minute sonicate. Compared with the application of doxorubicin alone, the doxorubicin cytoxicity was increased by 100-fold in SM cell cologenic survival assay when doxorubicin was combined with an intensity of ultrasound at 0. 8W/ cm2. CONCLUSIONS: The low intensity continuous wave ultrasound can obviously kill lung cancer cells and dramatically increase the cytotoxicity of doxorubicin for lung cancer cells. PMID- 21029584 TI - [The experience of surgical resection in 1964 cases of primary bronchogenic carcinoma]. AB - BACKGROUND: To summarize the experience of surgical resection of primary bronchogenic carcinoma (PBC) . METHODS: We reviewed the clinicopathologic data of 1 964 cases of PBC. There were 1 140 central type and 824 peripheral type. RESULTS: Among them, 1 626 cases ( 82. 8%, 1 626/ 1 964) were given successive resection, in which 160 cases were total pneumonectomy, 1 386 cases were lobectomy, 70 cases were sleeve lobectomy, and 10 cases were wedge resection. Two hundred and ninety2four cases had various postoperative complications and 20 cases died. The operative mortality was 1. 0%( 20/ 1 964) . Managements of problems encountered in operation were discussed in this paper. CONCLUSIONS: Surgical resection is a better apporach in the treatment of PBC. Left upper lung cancer invading and surrounding the pulmonary artery trunk requires blocking the pulmonary artery root first, then separating the invaded blood vessels and resecting the tumor and upper pulmonary lobe, lastly dealing with the remained cancer tissues. For patients with intermediate and advanced lung cancer, if the root of pulmonary artery and vein almost attaches to the tumor, intrapericardial blood vessels ligation should be performed. When the right upper lung cancer invades and surrounds the superior vena cava and the upper pulmonary artery trunk, we should cut and ligate the azygos vein first and draw the superior vena cava gently towards front outside and dissect carefully. If the tumor, hilar, mediastinal and associated lymph nodesmix together to formthe frozen hilar, we should deal with the main bronchus first, then the pulmonary artery and vein. PMID- 21029585 TI - [Results of surgical treatment of 220 patients with lung cancer]. AB - BACKGROUND: To explore the prognostic factors in the patients with lung cancer who were surgically treated. METHODS: Two hundred and twenty patients with lung cancer were treated with surgical treatment. Of the whole group , exploratory operation was performed in 15 cases and radical resection was done in 205 cases (93. 2 %) . RESULTS: The follow-up rate was 95. 8 %. The 1- , 5- , 10- and 20 year survival rate were 88. 3 %,45. 6 %,26. 2 % and 15. 4 % respectively. The prognosis of the patients was closely correlated with P-TNM stage , lymph node status and pathological classification ( P < 0. 01) , but not with extent of resection ( P > 0. 05) . CONCLUSIONS: The prognosis of patients with lung cancer surgically treated is remarkably related to P-TNM stage , pathological classification and the mediastinal lymph node status. PMID- 21029586 TI - [Study on influencing prognostic factors of surgical treatment in patients with lung cancer]. AB - BACKGROUND: To study the influencing prognostic factors in surgical treatment for lung cancer. METHODS: From January , 1961 to December , 1988 , the clinical data of 946 patients who underwent operation for lung cancer were analyzed by Life table , Log-rank test and Cox regression model. Twenty-nine potential prognostic factors were evaluated with SAS 6. 12 software. RESULTS: Overall 5-year survival rate was 47. 8 %. The 5-year survival rates of patients with stage I, II, IIIA were 61. 7 % , 35. 5 % and 27. 6 % respectively ( P < 0. 01) . Number of metastatic lymph nodes and tumor size were regarded as two independent prognostic factors. The 52year survival rates of patients with radical and palliative resection were 52. 2 % and 25. 1 % respectively( P < 0. 01) . The 5-year survival rates for different pathological types were as follows : squamous cell carcinoma , 54. 0 %; adenocarcinoma , 44. 0 %; small cell lung cancer, 42. 0 %; adenosquamous carcinoma , 36. 5 %; and large cell lung cancer , 23. 5 % ( P < 0. 05) . CONCLUSIONS: The influencing prognostic factors in surgical treatment for lung cancer are P-TNM staging , number of metastatic lymph nodes , radical or palliative resection , tumor size and pathological types of the cancer. PMID- 21029587 TI - [Clinical analysis of pregnancy complicated with severe thrombocytopenia]. AB - OBJECTIVE: To investigate the etiology and perinatal outcome of pregnancies complicated with extremely severe thrombocytopenia [at least two times of platelets count (PLT) < 10 * 10(9)/L during pregnancy]. METHODS: Clinical data, including basic information, etiology, management and outcomes of pregnant women with extremely severe thrombocytopenia, admitted to Peking University People's Hospital from January 2004 to March 2009, were retrospectively collected. The management of these cases varied according to different etiology and the symptoms: (1) PLT were maintained > 20 * 10(9)/L and hemoglobulin > 70 g/L in those women without spontaneous bleeding; (2) PLT transfusion would be required when PLT < 10 * 10(9)/L or bleeding occur and RBC would be supplied when hematocrit < 25% and hemoglobulin < 70 g/L; (3) Hemoglobulin should be > 70 g/L and PLT > 30 * 10(9)/L before cesarean section or delivery; (4) Predinisone and/or intravenous immunoglobulin G (IVIG) would be given in women complicated with idiopathic thrombocytopenic purpura (ITP) when PLT < (20 - 30) * 10(9)/L or bleeding. PLT would be given if all the above management were failed, or PLT < 10 * 10(9)/L, or bleeding. Women without bleeding would be closely monitored and delivery would be planned. RESULTS: (1) Twenty-six cases were identified among 9302 deliveries during the study period (0.28%), with an average of maternal age of 29. Seventeen were diagnosed before conception and 9 during pregnancy. Among the 26 women, half received regular prenatal check in our hospital and the average gestations at diagnosis was 24 weeks and the other half without regular prenatal visits and the average gestations at diagnosis was 32 weeks. Etiology was identified in 24 out of the 26 women, including 14 (54%) ITP, 5 myelodysplastic syndrome (MDS), 4 chronic aplastic anaemia (CAA) and 1 systemic lupus erythematosus (SLE). (2) MANAGEMENT: All of the 26 women received blood products. Among the 14 ITP cases, 6 received predinisone and IVIG and 8 only took predinisone. Nine of the 26 patients (35%) had pregnant complications, among which 6 (6/9) were preeclampsia. The overall average gestation at delivery was 36 weeks. Only 2 delivered vaginally with the average blood loss of 83 ml and 23 cesarean sections were performed with the average blood loss of 410 ml. (3) Perinatal outcomes: There were 26 perinatal babies, among which 1 died intrauterine and 25 were born alive (12 preterm infants). The average birth weight was 2877 g. Neonatal severe thrombocytopenia presented in 2 newborns whose mother complicated with ITP. CONCLUSIONS: The main cause of extremely severe thrombocytopenia during pregnancy is ITP, managed mainly by predinisone and IVIG, followed by CAA and MDS, which may require supportive treatment. Pregnancy complicated with extremely severe thrombocytopenia is not an indication of termination. Better maternal and fetal outcomes can be achieved through proper treatment based on the etiology, intensive care in prevention and management of complications and cesarean section. PMID- 21029588 TI - [Expression of suppressor of cytokine signaling 3 and its significance in human placenta with pregnant intrahepatic cholestasis]. AB - OBJECTIVE: To detect the expression and significance of suppressor of cytokine signaling 3(SOCS3) in the placentas of pregnant women with intrahepatic cholestasis of pregnancy (ICP). METHODS: Totally, 44 ICP gravidas, including 21 severe ICP and 23 mild ICP who delivered through cesarean section at the Second Xiangya Hospital of Central South University from April 2008 to January 2009, were selected as the ICP group, and another 25 healthy pregnant women were chosen as control. Placentas of the above gravidas were collected and the expression and localization of SOCS3 were determined by immunohistochemical peroxidase streptomyces-avidin link (SP) method (indicated by the percentage of positive cells and average gray scale) and the levels of interleukin-10 (IL-10) and interferon-gamma (IFN-gamma) from placenta homogenation were measured by enzyme linked immunoadsorbent assay (ELISA). RESULTS: (1) SOCS3 were expressed in placentas of both groups mainly in the intracytoplasma of trophocyte. However, weakly positive, positive, and strongly positive expressions were found in the severe ICP, mild ICP and the control group, respectively. Almost no expression was detected in membrane and nucleus of the trophoblasts. (2) The percentage of SOCS3 positive cells in the severe ICP group was significantly lower than in the control and the mild ICP group, respectively [(0.15 +/- 0.08) % vs (0.69 +/- 0.12) % and (0.42 +/- 0.09) %, P < 0.01]. The average gay SOCS3 in placental tissue in the severe ICP group was significantly higher than that in control and mild ICP group, respectively (204 +/- 7 vs 81 +/- 7 and 147 +/- 7, P < 0.01). (3) Significant lower level of IL-10 in placenta homogenation was found in the severe ICP group than in the control and mild ICP group [(1.16 +/- 0.68) ug/L, vs (1.39 +/- 0.08) ug/L and (1.22 +/- 0.75) ug/L, P < 0.01]. (4) The opposite results were found in the level of IFN-gamma in trophoblasts and the ratio of IFN-gamma/IL-10 [severe ICP group: (16.8 +/- 0.7) ug/L and 16.02 +/- 2.79; control group: (10.5 +/- 0.3) ug/L and 8.56 +/- 0.14; mild ICP group: (13.4 +/- 0.5) ug/L and 8.56 +/- 0.14, P < 0.01]. (5) Negative correlation was shown between the percentage of SOCS3 positive cells in trophoblasts and the ratio of IFN-gamma/IL-10 (r = -0.685 and -0.702, P < 0.01), and the average gay SOCS3 was positively correlated with the ratio of IFN-gamma/IL-10 (r = 0.621 and 0.891, P < 0.01) in both mild and severe ICP group. CONCLUSIONS: SOCS3 may participate in the pathogenesis of ICP and its expression may affected by the severity of ICP, and SOCS3 may also play a role in the immunological regulation in ICP patients. PMID- 21029589 TI - [Effects of di-(2-ethylexyl) phthalate on apoptosis of cytotrophoblasts in early pregnancy]. AB - OBJECTIVE: To investigate the influence of di-(2-ethylexyl) phthalate (DEHP) on cell apoptosis and expression of Bcl-2 and bax in cultured human first trimester cytotrophoblasts. METHODS: Human first trimester cytotrophoblasts were cultured with DEHP at concentration of 0, 25, 50, 100 umol/L for 24 hours. Cell apoptosis was detected by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) and flow cytometer method. The expression of apoptosis-associated genes, including Bcl-2 and bax, were detected by reverse transcription (RT)-PCR in cultured cytotrophoblast cells. The protein expression of Bcl-2 and bax in cytotrophoblast cells was measured by western blot. RESULTS: (1) The expression of Bcl-2: when incubated with DEHP at concentration of 0, 25, 50 and 100 umol/L, the expression of Bcl-2 were 1.00 +/- 0.05, 1.03 +/- 0.04, 1.04 +/- 0.03, 1.04 +/- 0.04, which did not show statistical difference (P > 0.05). The expression of Bcl-2 protein were 0.11 +/- 0.02, 0.11 +/- 0.04, 0.12 +/ 0.02, 0.12 +/- 0.03, which also didn't reach statistical difference (P > 0.05). (2) The expression of bax: when incubated with DEHP at concentration of 50 and 100 umol/L, the expression of bax protein were 0.63 +/- 0.04 and 0.81 +/- 0.04, which were significantly higher than 0.23 +/- 0.05 with DEHP at 0 umol/L (P < 0.05). The expression of bax mRNA were 0.96 +/- 0.04 and 1.02 +/- 0.04, which was significantly higher than 0.81 +/- 0.05 with DEHP at 0 umol/L (P < 0.05). (3) Apoptosis: when incubated with DEHP at concentration of 50 and 100 umol/L for 24 hours, the apoptotic cell ratio were (18.8 +/- 2.6) % and (20.3 +/- 2.0) % by annexin V-FITC/PI staining, which were significantly higher than (10.6 +/- 1.4) % at 0 umol/L and (18.1 +/- 4.6) % and (19.5 +/- 1.2) % by TUNEL staining, which were significantly higher than (11.2 +/- 3.1) % at 0 umol/L of DEHP (P < 0.05). CONCLUSION: DEHP could induce apoptosis of cytotrophoblast cells by increasing bax gene expression, but had no effect on Bcl-2 expression. PMID- 21029590 TI - [Survey on menopausal age and menstruation span in women in Pudong district of Shanghai]. AB - OBJECTIVE: To investigate natural spontaneous menopausal age, menstruation span and their relationship with menarche age and parity in Pudong district of Shanghai. METHODS: From Jan 2007 to Jul 2008, 15 083 spontaneous menopause women undergoing cervical cancer screening were enrolled in this study. The questionnaire included menarche age, parity, spontaneous menopausal age and menstruation span. Those women were divided into four groups based on age, which were group of 56 - 60, 61 - 65, 66 - 70 and more than 70.Analysis of variance (ANOVA) was used for comparing difference between menopausal age and menstruation span. Multiple factor regressions was used to analyze the relationship between menarche age, parity and menopausal age and menstruation span. RESULTS: (1) Spontaneous menopausal age: the minimum was 29 years old, the maximum was 61 years old, and the mean age was (50.6 +/- 3.7) years old. The mean spontaneous menopause age were (50.9 +/- 3.4), (50.7 +/- 3.7), (50.0 +/- 4.1), (49.6 +/- 4.0) years in groups of 56 - 60, 61 - 65, 66 - 70 and more than 70 years. With the increasing age range in four groups, the increasing trends of menopausal age were observed, which the difference of 1.36 year was shown between groups of 56 - 60 and more than 70 years. (2) Menstruation span: the mean of menstruation span was (34.3 +/- 4.1) years, which the minimal age of 12 years and maximal age of 48 years were recorded. (34.6 +/- 3.8), (34.3 +/- 4.1), (33.9 +/- 4.6), (33.2 +/- 4.5) were observed in groups of 56 - 60, 61 - 65, 66 - 70 and more than 70 years. With the increasing age range in four groups, the increasing trends of menstruation span were observed, which the difference of 1.41 year was shown between groups of 56 - 60 and more than 70 years. (3) The impact of menarche age on menopausal age and menstruation span: there was no correlation between menarche age and menopausal age (r = 0.02); however, menstruation span was found to be negatively correlated with the menarche age (r = -0.43). (4) The impact of parity on menopausal age and menstruation span: the mean menopausal age of women who had 1 - 2 deliveries was significantly higher than those had no delivery or more than 3 deliveries (P < 0.05). However, there was no difference in menopausal age between women with 1 and 2 deliveries or between women without delivery and more than 3 deliveries (P > 0.05). Menstruation span of women with 1 delivery was significantly longer that those with more than 1 delivery (P < 0.05), similarly, women with 2 deliveries had longer menstruation span than women without delivery or more than 3 deliveries (P < 0.05). There were no difference in menstruation span between women with more than 3 deliveries and without delivery (P > 0.05). (5) Multifactor regression analysis for menstruation span: menarche age was correlated with menstruation span negatively (r = -0.97, P < 0.001). There was significantly different menstruation span between group of 61 - 65, 66 - 70 or more than 70 years and group of 56 - 60 (r = -0.18, P = 0.020; r = -0.78, P < 0.001 and r = -1.23, P < 0.001). Menstruation span in women with 1 - 2 deliveries was significantly longer than that of women without delivery or more than 3 deliveries. (6) Multifactor logistic analysis of menopausal age: there was no association between menarche age and menopausal age, however, significant differences were found in mean menopausal age between different groups, which show that menopausal age of group 56 - 60 years was significant higher than the other groups, including age-group 61 - 65 years, 66 - 70 years and over 70 years (r = -0.18, P = 0.020; r = -0.78, P < 0.001; r = -1.23, P < 0.001). Menopausal age in women with 1 - 2 deliveries was significantly higher than those of women without delivery or with more than 3 deliveries, however, no difference between women with 1 and 2 deliveries or between women without deliveries and more than 3 deliveries was observed. CONCLUSION: (1) Menopausal age and menstruation span exhibited increasing trends in Pudong district of Shanghai. (2) Menarche age and parity were the important factors influencing menopausal age and menstruation span. (3) With younger age of menarche, the menstruation span become longer.(4) Deliveries of 1 - 2 times can significantly delay the menopause and prolong menstruation span, however, the multiple deliveries (>= 3 times) had no significant impact on menopausal age and menstruation span. PMID- 21029591 TI - [Use of recombinant human luteinizing hormone for ovulation stimulation in in vitro fertilization-embryo transfer]. AB - OBJECTIVE: To evaluate application of recombinant human luteinizing hormone (r hLH) used in ovarian stimulation of assisted reproductive technique and impact on outcome of pregnancy. METHODS: From Apr. to Jul. 2009, 123 patients with low LH level (< 1 U/L) at day 3 of menstruation and down-regulation of pituitary function undergoing in vitro fertilization-embryo transfer (IVF-ET) in Reproductive Medical Center, Provincial Hospital Affiliated to Shandong University were enrolled in this study, whom were classified into 66 cases treated by r-hLH in r-hLH group and 57 cases without r-hLH treatment in non-r-hLH group. In the mean time, 145 patients with normal level of serum LH (1 - 2 U/L) not given by r-hLH treatment and undergoing IVF-ET were matched as control group. Total amount of gonadotropin, estradiol levels and LH levels on the administration of human chorionic gonadotropin (hCG), number of oocytes retrieved, number of 2PN zygotes, rate of high quality embryos, the rates of implantation and clinical pregnancy were compared among these three groups. RESULTS: The level of serum LH on the day of hCG administration were (1.59 +/- 0.77) U/L in r-hLH group, (0.54 +/- 0.25) U/L in non-r-hLH group and (2.39 +/- 1.01) U/L in control group, which reached statistical difference between every two groups (P < 0.05). The rates of high quality embryo were 59.36% in r-hLH group, 57.79% in non-r-hLH group, which were significantly lower than 65.94% in control group, respectively (P < 0.05). The rates of 2PN were 67.62% in r-hLH group and 68.32% in control group, which were significantly higher than 62.84% in non-r-hLH group, respectively (P < 0.05). The rates of implantation of 29.77% in r-hLH group were significantly higher than 18.26% in non-r-hLH group (P < 0.05). The total amount of gonadotropin, estradiol level on the day of hCG administration, the number of oocytes retrieved, and clinical pregnancy rate were not significantly different among those three groups (P > 0.05). CONCLUSION: The administration of recombinant human luteinizing hormone in patients who are profoundly suppressed after down-regulation with long protocol can get more quality embryos, the higher rates of 2PN and implantation. PMID- 21029592 TI - [Association of human papillomavirus infection with other microbial pathogens in gynecology]. AB - OBJECTIVE: To Investigate correlation between screening assay of human papillomavirus (HPV) and microbial pathogens in gynecology. METHODS: Cervical samples were collected to search for HPV, bacteria and yeast infections in gynecologic outpatients. HPV typing was carried out by PCR and sequencing on cervical brush specimens. Chlamydia trachomatis was identified by strand displacement amplification (SDA) and the other microorganisms were detected by conventional methods. All data were analyzed to investigate the correlation among them. RESULTS: In this cross-sectional study, among 857 enrolled outpatients, there were 266 cases with positive HPV DNA, and the rate of infection was 31.0% (266/857). HPV genotype showed that thirty-five different HPV types were identified, of which HPV16 was the most prevalent (14.5%, 38/262), followed by HPV58 (9.2%, 24/262), HPV53 (8.0%, 21/262) and HPV42 (6.1%, 16/262); while other genotypes were present in less than 5% of HPV positive women. According to the reclassification, the aggregated percentage (high-risk and probably high-risk) of detected HPV was 58.8% (154/262), 27.9% (73/262) for low-risk and 13.4% (35/262) for unknown-risk HPV types. Among HPV positive women, cervical brush specimens results showed that more than 60% cases with normal cytology, 3.8% (10/266) with high-grade squamous intraepithelial lesions (HSIL), 29.7% (79/266) with low-grade squamous intraepithelial lesions (LSIL) and 3.0% (8/266) with atypical squamous cells of undetermined significance (ASCUS), respectively. Statistical analyses revealed there was a significant association between the infected HPV and Chlamydia trachomatis or Ureaplasma urealyticum (> 10,000 CCU/ml; all P < 0.01), while no correlation was found between HPV infection and bacterial vaginosis, streptococcus agalactiae, candida, Trichomonas vaginalis or Ureaplasma urealyticum (<= 10 000 CCU/ml; all P > 0.05). Among the cases with bacterial vaginosis, the positive rate of HPV infected was 42.6%. Chlamydia trachomatis was one of the high-risk factors for the infection of HPV (OR = 2.82, 95% CI: 1.74 - 4.57). Mycoplasma hominis was isolated only in 2 cases, no patient was infected with Neisseria gonorrhoeae. CONCLUSIONS: Although bacterial vaginosis was not significantly associated with HPV, it was more common among the HPV positive women. There is the significant association between HPV and Chlamydia trachomatis or Ureaplasma urealyticum which may be increase the infection of HPV. These data suggest that it may be important to screen for the simultaneous presence of different microorganisms which may have synergistic pathological effects. PMID- 21029593 TI - [Expression of glyoxalase I and its effect on cell proliferation and apoptosis in endometrial carcinoma]. AB - OBJECTIVE: To examine the expressions of glyoxalase I (GLO-I) in endometrial cancer tissues and cell lines and to investigate the roles of GLO-I on proliferation and apoptosis in endometrial cancer cells. METHODS: Immunohistochemistry, western blot and RT-PCR were used to investigate the expressions of GLO-I protein and mRNA in endometrial cancer tissues and Ishikawa cell lines;enzyme activity of GLO-I in normal endometrium, endometrial cancer and paraneoplastic tissue samples was detected with spectrophotometer;proliferation and apoptosis of Ishikawa cell before and after RNA interference (RNAi) procedure were detected by the methyl thiazolyl tetrazolium (MTT) and flow cytometry, respectively. RESULTS: (1) There were significant differences of GLO-I expression between normal endometrium (0/19) and endometrial cancer tissues (76%, 22/29); these were also significant differences of enzyme activity of GLO-I among normal endometrium, paraneoplastic and endometrial cancer tissues (1.1, 0.8 vs 92.3 IU/mg; P < 0.01). Enzyme activity of GLO-I in fresh normal endometrium and paraneoplastic tissues was weak, while that of fresh endometrial cancer tissues was as high as 92.3 IU/mg in average. (2) The expression of GLO-I mRNA in Ishikawa cell transfected with GLO-I siRNA was significantly lower than that in negative group (0.25 +/- 0.06 vs 0.93 +/- 0.10, P < 0.01), and the similar results that in the expression of GLO-I protein (0.38 +/- 0.06 vs 0.94 +/- 0.13, P < 0.01). (3) Proliferation in Ishikawa cell was significantly inhibited after silencing RNA expression of GLO-I (P = 0.028). The apoptosis rate of cells transfected with GLO-I siRNA was significantly higher than that of negative control group and blank control group [(6.7 +/- 0.8) % vs (1.2 +/- 0.4)%, (1.4 +/ 0.4)%; P < 0.01]. CONCLUSION: The expression and enzyme activity of GLO-I is significantly increased in endometrial cancer, which could promote abnormal proliferation and inhibit apoptosis in endometrial cancer cells. PMID- 21029594 TI - [A multi-center randomized controlled trial of three types of intrauterine device inserted immediately after vacuum aspiration]. AB - OBJECTIVE: To compare the safety and effectiveness of three types intrauterine device (IUD) insertion immediately after vacuum aspiration, and to provide evidence for women fulfilling contraception and reducing repeat abortion. METHODS: A multi-center randomized controlled clinical trial was performed in 12 medical institutions or family planning service stations located in China. Total 1800 eligible women were inserted G-Cu200, TCu380A or active gamma-IUD randomly after vacuum aspiration immediately, and they were followed up for 12 months. RESULTS: Except for 2 cases who dropped out (loss rate is 0.11%, 2/1800) and 17 cases who didn't match the including standard, the data of 1781 cases was analyzed. No any uterine perforation or ectopic IUD was found. During followed up 12 months, there was also no any pregnancy or pregnancy with IUD in situ occurred in the three groups. The medical removal rate for bleeding or (and) pain of active gamma-IUD was the lowest (1.02/hundred women year) among three groups, and there were significant difference (P = 0.015). The rate of expulsion rate and discontinuation rate of active gamma-IUD was 2.73/hundred women year, which was also the lowest among the three IUD, but there was no significantly statistical difference (P > 0.05). CONCLUSIONS: The results showed that there are perfect clinical safety and effectiveness for three types of IUD immediately after vacuum aspiration. Active gamma-IUD is superior to other two types IUD for its low medical removal rate which may be worthy to use widely immediately after vacuum aspiration. PMID- 21029595 TI - [Interaction among peroxisome proliferators-activated receptor alpha, cytochrome P450 oxysterol 7alpha-hydroxylase and estrogen receptor and its association with intrahepatic cholestasis in pregnant rats]. AB - OBJECTIVE: To investigate the relationship between interaction of peroxisome proliferators-activated receptor alpha (PPARalpha), cytochrome P450 oxysterol 7alpha-hydroxylase (CYP7B1) and estrogen receptor (ER) and intrahepatic cholestasis in pregnant rats. METHODS: Eighty clean SD pregnant rats were selected and divided into four groups randomly with 20 in each. Since the 13th day of pregnancy, rats in the control group was injected subcutaneously with refined vegetable oil 2.0 ml*kg(-1)*d(-1), those in the low-dose, moderate-dose and high-dose groups received 17-alpha-ethynylestradiol (EE) 1.0 mg*kg(-1)*d(-1), 1.25 mg*kg(-1)*d(-1) and 1.5 mg*kg(-1)*d(-1), respectively. All rats were sacrificed at the 21(st) day of pregnancy and maternal hepatic tissues were collected. The serum levels of alanine aminotransferase (ALT), aspartate transaminase (AST), total bile acid (TBA) and bilirubin (BIL) were determined by enzyme linked immunosorbent assay (ELISA). The mRNA expressions of PPARalpha, CYP7B1, ERalpha and ERbeta in maternal rat livers were examined by real-time PCR. RESULTS: (1) Biochemical indicators: the serum levels of ALT, AST, TBA and BIL were significantly lower in the control group than in the rest 3 groups, respectively [control group: (41.1 +/- 2.8) U/L, (44.4 +/- 3.6) U/L, (26.4 +/- 5.6) umol/L and (2.8 +/- 0.2) U/L; low-dose group: (48.2 +/- 3.4) U/L, (47.9 +/- 3.7) U/L, (36.4 +/- 4.2) umol/L and (4.2 +/- 0.2) U/L; moderate-dose group: (70.4 +/- 5.3) U/L, (68.4 +/- 5.6) U/L, (64.3 +/- 3.8) umol/L and (6.2 +/- 1.2) U/L; high-dose group: (72.4 +/- 7.6) U/L, (70.2 +/- 3.8) U/L, (72.4 +/- 7.8) umol/L and (8.2 +/- 2.2) U/L, P < 0.05], and those in the moderate or high-dose groups were higher than in the low-dose group (P < 0.05). (2) mRNA expression of ERalpha and ERbeta: the mRNA expression of ERalpha in pregnant rat livers increased in a dose-dependent manner, which were all significantly higher than that in the control group, respectively (low-dose group: 0.76 +/- 0.02); moderate-dose group: (0.99 +/- 0.04; high-dose group: 1.21 +/- 0.01; control group: 0.65 +/- 0.01, P < 0.05), but no difference was found among the 4 groups in the mRNA expression of ERbeta (P > 0.05). (3) mRNA expression of CYP7B1 and PPARalpha: the mRNA expression of CYP7B1 in pregnant rat livers increased from the low-dose group to the high-dose group, and were all higher than that of the control group (low-dose group: 0.93 +/- 0.01; moderate-dose group: 0.99 +/- 0.06; high-dose group: 1.22 +/- 0.04; control group: 0.75 +/- 0.02, P < 0.05). However, the mRNA expression of PPARalpha decreased from the low-dose group to the high-dose group, and were all lower than that of the control group (low-dose group: 0.83 +/- 0.05; moderate dose group: 0.71 +/- 0.02; high-dose group: 0.64 +/- 0.03; control group: 1.35 +/ 0.05; P < 0.05). CONCLUSIONS: The down regulated mRNA expression of PPARalpha, caused by higher dose of estrogen, may increase the expression of CYP7B1 due to the ineffectiveness of the inhibition of PPARalpha on CYP7B1, which may further stimulate the ERalpha activity and then induce intrahepatic cholestasis. Abnormal expression of PPARalpha, CYP7B1 and ER may play a role in the pathogenesis of estrogen-induced intrahepatic cholestasis. PMID- 21029596 TI - [Proteasome inhibitors sensitize ovarian cancer cells to cisplatin]. AB - OBJECTIVE: To explore the sensitivity and the molecular mechanism of cisplatin resistance ovarian cancer cell line C13 to proteasome inhibitors and the combination with cisplatin. METHODS: After different treatments, methyl thiazolyl tetrazolium (MTT) assay was applied to examine the cell viability, annexin V/propidium iodide (PI) apoptosis detection kit was used to determine the apoptosis rate of different groups, western blot assay was introduced to evaluate the expression levels of Fas-associated death domain-like interleukin-1 beta converting enzyme inhibitory protein (cFLIPs), and the activity of caspase-8 was examined. RESULTS: MTT assay shown that the cell viability ratios of combination group at serial time points from 12, 24, 36, 48, 60, 72 hours were (56.0 +/- 8.4) %, (44.7 +/- 7.3) %, (33.7 +/- 11.2) %, (27.6 +/- 8.0) %, (27.6 +/- 7.6) % and (28.1 +/- 2.4) %, which were much lower than those of cisplatin group (P < 0.05). After treated for 24 hours, apoptosis rates of cisplatin group, bortezomib group and combination group were (16.7 +/- 1.7) %, (23.4 +/- 2.1) % and (26.9 +/- 1.6) %, respectively. The rate of combination group was much higher than that of non treated group and that of cisplatin group or bortezomib group (P < 0.05). Western blot assay showed the changes of expression levels of cFLIPs, which were down regulated seriously after cisplatin, bortezomib or combination treatment [(43.2 +/- 2.3) % vs (75.7 +/- 3.0) % vs (67.9 +/- 2.1) %, P < 0.05]. The caspase-8 activity of combination group was (5.6 +/- 1.6) folds than that of non-treated group, which was higher than those of other two groups [(2.3 +/- 1.0) and (4.2 +/ 0.9) folds, P < 0.05]. CONCLUSIONS: The tumor cell lethal effect of cisplatin could be increase significantly by the combination application of proteasome inhibitors, bortezomib. And the cFLIPs/caspase-8 signaling pathway may be play an important role in the molecular mechanism of the combination treatment. PMID- 21029597 TI - [Establishment of multiple quantitative fluorescent polymerase chain reaction assay and its application in rapid prenatal diagnosis of common chromosome aneuploidies]. AB - OBJECTIVE: To establish the multiple quantitative fluorescent polymerase chain reaction (QF-PCR) assay and evaluate its clinical application in prenatal diagnosis. METHODS: Totally 170 samples were collected between May 2008 and July 2009 in prenatal center of Peking Union Medical College Hospital; 123 of them were amniotic fluid, 9 were chorionic villous samples, 20 were fetal blood and 18 were villi from aborted fetuses. All samples were from women of Han nationality, with mean age of (34.1 +/- 4.6) years old, and with mean gestational age of (19.6 +/- 1.0) weeks. Cytogenetic cultures and karyotyping were made to every sample. Genomic DNA was extracted from the samples. The sequences of twenty short tandem repeat (STR) markers were designed according to the GenBank and references, including 6 STR markers in chromosome 21, 4 in chromosome 18, 4 in chromosome 13, 4 in chromosome X, 1 in chromosome Y and 1 universal marker in both X and Y chromosome. Each sample was amplified by two sets of multiple QF-PCR, which included 4 STR markers in each of 21, 18, 13 and sex chromosomes. If the result was uninformative, the third set of another 4 STR markers was added. RESULTS: (1) Karyotyping. Cytogenetic analysis were made for all the 170 samples, 151 (89%) of which were normal, and 19 (11%) were abnormal. (2) QF-PCR assay. 167 (98%) samples were detected by QF-PCR. The results were obtained within 2 - 3 days after sampling. 134 samples were proved normal by QF-PCR, which was consistent with karyotyping. Among the 19 abnormal karyotype samples, 18 were detected as abnormal(eight were 21-trisomy, three were 18-trisomy)by QF-PCR. Among the 167 samples, 150 (90%) were detected using the first and second set of STR mixtures, and 3 (2%) were detected when the third set of STR was added. The remain 14 (8%) were uninformative. (3) The diagnostic efficiency of QF-PCR. The sensitivity of QF-PCR in prenatal diagnosis of common aneuploidities was 95%, the specificity, the false positive rate, the false negative rate, the positive predictive value and negative predictive value were 100%, 0, 5%, 100% and 99%, respectively. (4) Autosome and sex chromosome detection by QF-PCR. Among all the STR markers, D21S1270 and D21S1411 had the highest heterozygosities in chromosome 21, and DXS8377 had the highest in sex chromosome. The amplifications were stable. CONCLUSION: Multiple QF-PCR assay is a valid alternative in rapid prenatal diagnosis of common chromosome aneuploidies. With high accuracy, it can be used for numerous sample test in large-scale laboratories. PMID- 21029598 TI - [Evaluation the significance of body mass index in diagnosing macrosomia in human neonate]. AB - OBJECTIVE: We compared the difference of diagnosing macrosomia using the body mass index (BMI) and body mass, so as to investigate whether BMI play an important role in the diagnosis and management of macrosomia in our clinical work. METHODS: We analysed 5522 newborns (without any maternal complication) delivered in Shengjing Hospital of China Medical University from Jan. 2004 to Apr. 2009, all of them were full term, singleton and with the birth body mass larger than 2500 g, among them 4989 were in the group with body mass < 4000 g, that was 2510 - 4000 g. 533 cases were in the group of body mass >= 4000 g. By both body mass and length, we got the BMI. According to statistical receiver operating characteristic curve (ROC), we determined the cutoff of BMI for diagnosing macrosomia, in addition the sensitivity and specificity of it.Using this newly gotten BMI cutoff as a method to diagnose macrosomia and analyse the results. RESULTS: (1) When the newborns with birth length 40 - 43 cm, the mean birth body mass was (3010 +/- 351) g, BMI was (17.0 +/- 2.7) kg/m(2); the newborns with birth length 48 - 51 cm, the mean birth body mass was (3450 +/- 313) g, BMI was (13.2 +/- 1.4) kg/m(2); newborns with birth length 56 - 60 cm, the mean birth body mass was (4332 +/- 456) g, BMI was (12.5 +/- 1.3) kg/m(2). The longer the birth length, the larger the birth body mass, while the less BMI. (2) Determined by ROC curve, the BMI value could be used to diagnose macrosomia was 14.2 kg/m(2), with sensitivity of 78.4% and specificity of 85.0%, the area of under curve was 0.892. (3) By the BMI cutoff (14.2 kg/m(2)), 111 macorsomia with birth body mass >= 4000 g were not macrosomia any more (20.8%, 111/533), 422 still were macrosomia (79.2%, 422/533); while for those birth body mass < 4000 g, 728 were macrosomia determined by this BMI cutoff (14.59%, 728/4989), 4261 were still not macrosomia (85.41%, 4261/4989). Using BMI cutoff 14.2 kg/m(2) to diagnose macrosomia, within the group of birth body mass >= 4000 g, their birth length in macrosomia and non macrosomia was (52.2 +/- 1.8) cm and (55.6 +/- 1.3) cm respectively, the difference was significant (P < 0.01); while within the group with body mass < 4000 g, the birth length of macrosomia and non-macrosomia was (49.0 +/- 2.2) cm and (50.8 +/- 2.2) cm respectively, the difference was significant as well (P < 0.01). The whole incidence of macrosomia was 20.83% (1150/5522) determined by this BMI cutoff. CONCLUSIONS: Birth body mass and BMI in determining macrosomia show some bias, and birth length relates with this difference, which suggests birth length maybe play an important role in determine the macrosomia. We suggest it is very necessary to use BMI >= 14.2 kg/m(2) in the diagnosis and management of macrosomia. PMID- 21029599 TI - [Clinical study on dinoprostone suppositories 0.8 mm used in cervical ripening and labor induction of women with term pregnancy of premature rupture of the membranes: a multicenter study]. AB - OBJECTIVE: To investigate safety and efficacy of dinoprostone suppositories (0.8 mm) used in cervical ripening and labor induction in women with term premature rupture of the membranes. METHODS: One hundred women of term monocyesis with premature rupture of the membranes, head presentation, bishop score less than 6 (test group) and 180 women with intact fetal membranes (control group) were enrolled into this multicenter, prospective clinical study. The vaginal delivery system was inserted into the posterior fornix, and the patients were recumbent for 2 hours after insertion. The interval time from using dinoprostone suppositories to uterine contraction, to labor and delivery were recorded. The following index were also recorded and compared, including the mean inserted time of dinoprostone suppositories, fetal heart beat, meconium stained amniotic fluid, hyperstimulation of uterus and the other complications, mode of delivery, stage of labor, postpartum hemorrhage, status of neonates. RESULTS: Three cases in test group and 23 cases in control group weren't in labor within 24 hours. The rate of labor within 24 hours in test group was significant higher than that in control group (97.0% vs. 87.2%, P < 0.01). It was observed that 73 cases undergoing vaginal deliveries (75.3%, 73/97) and 24 cases undergoing cesarean section deliveries (24.7%, 24/97)in test group and 107 cases undergoing vaginal delivery (68.2%, 107/157) and 50 cases undergoing cesarean section delivery (31.8%, 50/157) in control group, when compared the rate of vaginal or cesarean section deliveries between two group, it didn't reach statistical difference (P > 0.05). It had no significant difference in the interval time from using dinoprostone suppositories to labor starting and the mean inserted time and the total labor time between two groups (P > 0.05). The incidence of uterine tachysystole was 11.3% (11/97) in test group and 19.1% (30/157) in control group (P > 0.05), which did not reach statistical difference (P > 0.05). There wasn't neonatal asphyxia in both groups. CONCLUSION: It was safe and efficient to use dinoprostone suppositories for cervical ripening and induction of term pregnancy with premature rupture of the membranes, however, monitoring should be intensified. PMID- 21029600 TI - [Clinical study on cervix biopsy guided by colposcopy in diagnosis of cervical diseases in pregnant women]. AB - OBJECTIVE: To investigate the value and safety of biopsy guided by colposcopy in diagnosis of cervical diseases in pregnant women. METHODS: From Aug. 2007 to Feb. 2009, 17 828 pregnant women who receive antenatal examination underwent cervical cytological screening thinprep cytology test (TCT) in Beijing Obstetrics and Gynecology Hospital. If abnormal cytological results were found, those pregnant women were administered by colposcopic examination and biopsy after they signed informed consent. RESULTS: (1) TCT: the abnormal TCT results of 1502 pregnant women (8.425%, 1502/17 828) were found in 17 828 cases. (2) Colposcopic examination: two hundred and four pregnant women underwent colposcopic examination. The rate of satisfied colposcopic imaging was 92.6% (189/204), colposcopic examination identified 125 cases with cervical inflammation or cervical intraepithelial neoplasia (CIN)I, 25 cases with CINII and 54 cases with CINIII or microinvasive squamous carcinoma (MIVC) of squamous cervical carcinoma (SCC). (3) The results of biopsy guided by colposcopy: among 204 cases, it was found 33 cases with cervical inflammation or wart, 95 cases with CINI, 28 CINII, 36 cases with CINIII and 12 cases with MIVC. (4) The rate of concordance: compared with biopsy pathologic examination, colposcopy examination found 113 cases with cervical inflammation and CINI, the rate of concordance was 90.4% (113/125). And 54 cases with CINIII or SCC diagnosed by colposcopy examination, however biopsy pathologic examination confirm 23 cases with CINIII and 10 cases with SCC at stage Ia, the concordance rate was 61% (33/54). (5) Complication: eight (3.9%, 8/204) pregnant women underwent cervical wound suturing due to continuous bleeding after colposcopy exam or biopsy. No other complications were recorded. CONCLUSIONS: It is necessary that TCT should be performed in pregnant women without cytological screening within one year. Colposcopic examination and biopsy were indicated if pregnant woman with abnormal cytological result were found. Pregnant women with cervicitis or CINI diagnosed by colposcopy should be followed up. If pregnant woman was suspected with CINII or advanced disease, biopsy guided by colposcopy should be performed. PMID- 21029601 TI - [Analysis of prevalence and risk factors of pelvic organ prolapse of women underwent gynecologic health care in Peking Union Medical College Hospital]. AB - OBJECTIVE: To investigate prevalence and risk factors of pelvic organ prolapse in women underwent routine gynecologic health care in Peking Union Medical College Hospital (PUMCH). METHODS: From Jan. 2008 to Aug. 2009, 972 women underwent gynecological health care in PUMCH were enrolled in this study. Questionnaires and pelvic examinations were given. The pelvic organ prolapse quantitive examination (POP-Q) system was used as the assessment tool. RESULTS: (1) Among all participants, the mean ages were (42 +/- 10) years (range 22 to 78 years), the mean height were (162 +/- 5) cm (range 142 to 180 cm), and the mean weight were (59 +/- 8) kg (range 42 to 91 kg). 83.8% (815/972) of women were multipara. The mean total vaginal length (TVL) of 972 women was 8.20 cm. No women met the standard of pelvic organ prolapse, while 35.5% (345/972) of women presented mild posterior vaginal descent and 96.7% (940/972) presented mild anterior vaginal descent, all of them were asymptomatic. (2) The length of genital hiatus (gh), TVL and C, D proximal to the hymen in nullipara were (2.26 +/- 0.32), (8.08 +/- 0.30), (-7.08 +/- 0.24) and (-8.08 +/- 0.30) cm, which were significantly less than (2.33 +/- 0.39), (8.22 +/- 0.35), (-7.14 +/- 0.28) and (-8.22 +/- 0.35) cm in multipara (P < 0.05). Ap and Pb proximal to the hymen of (-2.87 +/- 0.22) and (-2.87 +/- 0.22) cm in nullipara were significantly larger than (-2.81 +/- 0.25) and (-2.81 +/- 0.25) cm in multipara (P < 0.05). When compared with nullipara, the incidence of posterior and anterior vaginal wall protrusion were increased (OR = 1.819). (3) The index of POP-P were compared among women at groups of 22 - 34 years, 35 - 49 years and more than 50 years (P < 0.05). Those index did not show statistical difference between women at group of 22 - 34 years and group of 35 - 49 years (P > 0.05). However, those in women at group of 22 - 34 years and 35 - 49 years showed statistical difference when compared with women at group of more than 50 years (P < 0.05). When compared with women at group of 22 - 34 years, the incidence of posterior and anterior vaginal wall protrusion were increased (OR = 1.713, 3.765). (4) Menopause status was associated with severities of all kinds of descent (P < 0.05) and presence of posterior vaginal protrusion (OR = 3.354). CONCLUSIONS: Mild anterior and posterior vaginal descent by POP-Q were common among women in China. The risk of anterior vaginal descent is relatively higher than posterior vaginal descent. However, most of the women with descent are asymptomatic and need no treatment. The most important factors associated with the severity and detectable ratio of descent is parity and age. PMID- 21029602 TI - [Clinical value of the comprehensive treatment in intermediate and advanced cervical cancer with uterine arterial interventional chemoembolization and radiotherapy]. AB - OBJECTIVE: To investigate the long-term curative effect of the radiotherapy combined uterine arterial interventional chemoembolization for cervical cancer. METHODS: Records of 632 patients with cervical cancer stage II - IVa proved by pathology in Lanzhou Command General Hospital from January 1st, 1999 to August 31st, 2009 were retrospective analysed. One hundred and twenty-six cases of them were treated with radical radiotherapy combined uterine arterial interventional chemoembolization (arterial chemoembolization + radiotherapy group), 506 cases of them were treated with radical radiotherapy only (radiotherapy group); the evaluation of the late radiation injury was done, according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) advanced radiation injury criteria. Prognosis and complications were compared between two groups, relative risk factors of radiotherapy complications were identified by method of logistic regression. RESULTS: (1) Survival: the total survival rates of 1-year, 2-year, 5-year and 8-year were 94.4%, 82.3%, 48.8%, 29.1%, respectively. The survival rates of arterial chemoembolization + radiotherapy group were 96.0%, 82.1%, 37.2%, 25.7%, while the survival rates of radiotherapy group were 94.1%, 80.8%, 51.1%, 31.5%, in which there were significant differences between two groups (chi(2) = 0.009, P = 0.993; chi(2) = 0.158, P = 0.691; chi(2) = 11.197, P = 0.001;chi(2) = 9.649, P = 0.002). During the follow-up period, the rate of recurrence and metastasis in arterial chemoembolization + radiotherapy group were 77.0% (97/126), while 73.3% (371/506) in radiotherapy group (chi(2) = 0.705, P = 0.401). (2) Radiotherapy complications and relative risk factors: the total incidence of tardive bladder injury higher than RTOG/EORTC stage II was 5.5% (35/632), while it was 11.1% (14/126) in arterial chemoembolization + radiotherapy group, 4.2% (21/506) in the radiotherapy group (chi(2) = 9.344, P = 0.002). The results of logistic regression showed that the uterine arterial interventional chemoembolization was relative risk factors of the tardive bladder injury (chi(2) = 6.440, OR = 2.869, P = 0.011). CONCLUSIONS: Compared with the simple radiotherapy, there are a similar short-term survival rate and significant poor 5-year, 8-year survival rate in the patients treated with the uterine arterial interventional chemoembolization combined with radiotherapy, which also may be strong dangerous factor for the occurrence of tardive bladder injury. The results shown that the uterine arterial interventional chemoembolization do not recommend to be routine adjuvant therapy for the radical radiotherapy of cervical cancer. PMID- 21029604 TI - [Spontaneous clearance of high risk human papillomavirus infection]. AB - OBJECTIVE: To study the clearance of high risk human papillomavirus (HPV) infection among the women with normal cervical pathologic diagnosis. METHODS: One hundred and seventy-two HPV-positive cases with normal cervical pathologic diagnosis were enrolled in the study. The infection status of HPV was monitored during follow-up from Aug 2006 to Aug 2008. The time of HPV infection spontaneous clearance, as well as effect factors, were analyzed. RESULTS: During follow-up, there were 62.2% (107 cases, 107/172) of the HPV infection cleared. The medium clearance time was 11.3 months (95%CI: 10.6 - 16.6 months). The medium clearance time of aged < 30 years, 30 - 39 years, 40 - 49 years and > 49 years were 11.3, 12.0, 10.9 and 8.5 months, respectively. There were not significant difference among aged intervals (P = 0.384). The virus copies of HPV-clearance cases and persistent-infection were 22.6 and 95.0, respectively. There was not significant difference between groups (P = 0.061). CONCLUSIONS: Most of the high risk HPV infection with normal cervical pathologic diagnosis would spontaneously cleared. Age and HPV copies may play little role in the HPV clearance. PMID- 21029603 TI - [Clinical report of the modified Piver class III hysterectomy on invasive cervical cancer]. AB - OBJECTIVE: To explore the surgical extent and to improve the surgical techniques of the Piver class III hysterectomy on invasive cervical cancer, so as to reduce the urinary tract complications, shorten the surgical duration, decrease the hemorrhage and blood transfusion. METHODS: The study group, 196 cases with stages Ib and IIa carcinoma of the cervix underwent the modified Piver class III hysterectomy from June 2000 to May 2005. The control group, 176 cases of the same stages underwent the Piver class III hysterectomy between June 1994 and May 1999. The modified Piver class III hysterectomy mainly include the surgical extent and some surgical techniques as follows. The cervicovesical and vesicovaginal space are separated with assistance of electrotome. Half of the uterosacral ligaments are removed with electrotome. The tunnel of the ureters is separated and penetrated or not. The anterior leaf of the cervicovesical ligaments is removed and the uterine artery are removed at the same time, while the ureter branch from the uterine artery are preserved. When the ureters are drawn to the lateral side of the body with an "S" hook and the urocyst lateral recessus are expanded, the cardinal ligaments can be exposed and be removed of 3/4. But part of the inferior of these ligaments should be preserved. The paracolpium are resected about 2 cm, 2 - 3 cm tissue of the vagina is removed. RESULTS: Compare with the control group, the urinary tract complications of the study group were significantly reduced (51.1% versus 23.0%, P < 0.01). There were a shorter surgical duration [(132 +/- 20) min], less of the hemorrhage [(322 +/- 100) ml] and blood transfusion [(154 +/- 79) ml] in the study group than those in the control group (all P < 0.05). While, there was no significant difference at the survival rates of 5 years between the two groups (87.8% versus 88.6%, P = 0.793). CONCLUSION: The modified Piver class III hysterectomy is effective and applicable for patients with cervical cancer. PMID- 21029605 TI - [Lung metastasis of human choriocarcinoma in mice: establishment of experimental metastatic model and its biological characteristics]. AB - OBJECTIVE: To establish a satisfactory lung metastasis model of human choriocarcinoma using severe combined immunodeficient (SCID) mice and explore the appropriate cell concentration for the model. METHODS: Forty SCID mice aged between 5 - 6 weeks were randomly divided into four groups. 1 * 10(7) cells/ml * 0.1 ml, 5 * 10(6) cells/ml * 0.2 ml and 1 * 10(6) cells/ml * 0.1 ml of human choriocarcinoma cells JEG-3 were respectively injected in SCID mice of experimental groups by lateral tail vein, the remain group was assigned to the control group. The status and weight of mice were observed every three days. When these mice were being dying, the size and the number of the lesions of lung metastasis in every mouse were inspected with Micro CT. After Micro CT inspection, the SCID mice were executed dissected to note whether there were tumors on all organ surfaces with naked eyes, then made pathological sections from the metastatic foci of fresh lung tissues, and cultured primarily cells and purified cells and passaged cells isolated from the same metastastic foci. The pathological sections were observed under the microscope. The special antigen human chorionic gonadotropin-beta subunit (beta-hCG) of the choriocarcinoma cells was immunohistochemically detected in the pathological sections and the cells out of cultured primarily cells. The chromosomes of the cells out of cultured primarily cells were analysed. RESULTS: Of the group inoculated 1 * 10(7) cells/ml * 0.1 ml, all mice died when inoculating. In the group of 5 * 10(6) cells/ml * 0.2 ml, when inoculating, 3 mice died; the remain 7 mice were being dying on (18.0 +/- 2.0) days after injection. 5 of them, there were 1 - 3 lesions of lung metastasis after Micro CT inspection in each mice, and the diameter of the tumors lesions reached 1.5 - 3.5 mm, which was choriocarcinoma confirmed by pathological sections. The special antigen beta-hCG was detected by immunohistochemical method in the pathological sections of pulmonary tissue with tumor and in the cells, which were purified and passaged from being cultured primarily cells isolated from metastastic foci of fresh lung tissues from the SCID mice. The chromosome numbers of these cells out of cultured primarily cells were variety from 19 to 128, and modal numbers were variety from 70 to 79. CONCLUSIONS: We successfully established the lung metastatic model of human choriocarcinoma in SCID mice by injecting JEG-3 cells into lateral tail vein, of which 5 * 10(6) cells/ml * 0.2 ml is the suitable concentration and volume for the model. PMID- 21029607 TI - [Development of new research in gynecologic endocrinology through expanding horizons]. PMID- 21029606 TI - [Research of the characterization of Bcrp1(+) HeLa cells]. AB - OBJECTIVE: To make sure whether Bcrp1 is the marker of cervical cancer stem-like cells or not by studying the characterization of Bcrp1(+) HeLa cells. METHODS: Immunofluorescence stained flow cytometry and electron microscope were used to sort and observe ultrastructures of Bcrp1(+) and Bcrp1(-) HeLa cells. Flow cytometry was used to identify the cycle and the rate of apoptosis with annexin V in two group cells. The expression of proliferating cell nuclear antigen (PCNA) and caspase-3 were tested using western blot method. RESULTS: (1) There were 7.1% Bcrp1(+) cells and 92.9% Bcrp1(-)cells in HeLa cells. Bcrp1(+) HeLa cells were large in size of nuclear and nucleoli are clear, and there were rich of cytomicrosome and rough endoplasmic reticulum. After sorted and cultured for 24, 48, 72 hours, the adhesion in Bcrp1(+) cells were 72.8%, 81.1%, 80.4%, respectively. While, they were 3.3%, 18.7%, 12.6% at each time for Bcrp1(-) cells (all P < 0.05). (2) There are more S phase cells in Bcrp1(+) cells than that in Bcrp1(-) cells (54.1% vs 21.1%, P < 0.05), while the percentage of G(0)/G(1) and G(2)/M in Bcrp1(-) cells were higher than those in Bcrp1(+) cells (53.0% vs 44.4%, 25.9% vs 1.5%; all P < 0.05). The rate of apoptosis in Bcrp1(+) cells was lower than that in Bcrp1(-) cells (0.2% vs 5.3%, P < 0.05). (3) The expression of PCNA in Bcrp1(+) cells was higher than that in Bcrp1(-) cells (3140 vs 2255, P < 0.05), while the expression of caspase-3 of Bcrp1(+) cells was lower than that in Bcrp1(-) cells (1970 vs 3551, P < 0.05). CONCLUSION: There are more vigor and ability of proliferation and lower rate of apoptosis in Bcrp1(+) HeLa cells than those in Bcrp1(-) cells, which may be some characters of cervical cancer stem cells. PMID- 21029608 TI - [Highlights of the sixth national gynecological endocrinology summit of the Chinese Medical Association]. PMID- 21029609 TI - [Effect of luteinizing hormone vs follicular stimulating hormone ratio on anti Mullerian hormone secretion and folliculogenesis in patients with polycystic ovarian syndrome]. AB - OBJECTIVE: To investigate characteristics of anti-Mullerian hormone (AMH) secretion and mechanism of aberrant folliculogenesis by the ratio of luteinizing hormone (LH)/follicle-stimulating hormone (FSH) in polycystic ovarian syndrome (PCOS) patients. METHODS: Base on the ratio of LH/FSH, total 95 patients with PCOS were divided into two groups, including 49 cases in higher ratio group (LH/FSH >= 2) and 46 cases in normal ratio group (LH/FSH < 2) matched with 62 infertile cases with tubal factor and regular menstruation as control group. Body mass index (BMI) were calculated in all objectives. The serum AMH were detected by enzyme linked immunosorbent assay (ELISA). Ovarian sexual hormones, fasting blood glucose, insulin and lipid were measured by chemiluminescence method. The correlation between AMH and metabolic index was analyzed by multilinear regression. RESULTS: (1) AMH: the serum level of AMH were (7.2 +/- 4.3) ug/L in higher LH/FSH group, (5.2 +/- 3.8) ug/L in normal LH/FSH group and (3.7 +/- 2.2) ug/L in control group, which all reached significant difference among those 3 groups (P < 0.01). (2) The correlation between AMH and biological metabolic index: estradiol (E(2)) was negatively correlated with serum level of AMH in higher LH/FSH ratio group (r = -0.318). The serum level of AMH were positively correlated with BMI, fasting glucose, homeostasis model assessment insulin resistance index (HOMA-IR) in normal LH/FSH ratio group (r = 0.493, 0.362, 0.303). After controlling affect factors, serum levels of AMH were positively correlated with LH/FSH in higher LH/FSH ratio group (r = 0.301), but negatively correlated with E2 (r = -0.429). However, in normal LH/FSH group, serum level of AMH was only positively correlated with BMI (r = 0.428). CONCLUSION: The PCOS patients with higher LH/FSH ratio are primarily caused by hypothalamic-pituitary dysfunction, while the PCOS patients with normal LH/FSH ratio are mainly caused by metabolic disorders. PMID- 21029611 TI - [Characteristics of glucose metabolism in non-obese and obese women with polycystic ovarian syndrome]. AB - OBJECTIVE: To investigate characteristics of glucose metabolism of non-obese and obese women with polycystic ovary syndrome (PCOS). METHODS: From May 2006 to April 2009, 1928 PCOS patients treated in Reproductive Medicine Center of Shandong Provincial Hospital Affiliated to Shandong University were enrolled in this study, which were divided into 901 cases [body mass index (BMI) >= 25 kg/m2] in obese group and 1027 cases in non-obese (BMI < 25 kg/m(2)) group. The prevalence of type 2 diabetes mellitus (T2DM), oral glucose tolerance test, impaired fasting glucose (IFG), impaired glucose tolerance (IGT) were compared between the two groups. RESULTS: (1) Blood glucose levels: at the time of fasting, 30, 60, 120 and 180 minutes, the levels of glucose were (5.3 +/- 1.1), (9.0 +/- 2.4), (9.3 +/- 4.4), (7.5 +/- 2.8), (5.3 +/- 1.8) mmol/L in obese group and (5.0 +/- 0.8), (8.4 +/- 3.5), (8.0 +/- 4.2), (6.5 +/- 3.2), (4.9 +/- 1.6) mmol/L in non-obese group, which all showed statistical difference at every time point (P < 0.01). (2)The level of insulin: at the time of fasting, 30, 60, 120 min, the level of insulin were (13 +/- 7), (81 +/- 51), (102 +/- 65), (83 +/- 63) mU/L in obese group and (8 +/- 5), (57 +/- 35), (62 +/- 44), (46 +/- 39) mU/L in non-obese group, which all showed statistical difference at every time point (P < 0.01). However, at time point of 180 minutes, the level of insulin did not exhibit significantly difference between obese and non-obese group (P > 0.05). (3) The prevalence of abnormal glucose metabolism: the rate of IFG was 4.98% (96/1928). The rate of abnormal glucose tolerance was 23.08% (445/1928). The rate of IGT were 13.05% (134/1027) in non-obese group and 24.20% (218/901) in obese group, which also showed remarkable difference (P < 0.01). The rate of T2DM were 2.53% (26/1027) in non-obese group and 7.44% (67/901) in obese group, which reached significant difference (P < 0.01). CONCLUSION: Abnormal glucose metabolism was observed more frequently in overweight or obese PCOS women. PMID- 21029610 TI - [Clinical study on combination of multiple regimens in treatment of osteoporosis in perimenopause and postmenopausal women]. AB - OBJECTIVE: To evaluate clinical efficacy of multiple regimen combination in treatment of osteoporosis of perimenopausal or postmenopausal women. METHODS: From Jul. 2008 to Dec. 2009, 109 women with low bone mineral density (BMD) or osteoporosis treated in Department of Obstetrics and Gynecology, Affiliated Second Hospital, Wenzhou Medical College were enrolled randomly into 3 group, including 36 women in Group A managed by osteoform 1000 mg/d + alfacalcidol 0.25 ug/bid orally, 40 women in group B managed by osteoform 1000 mg/d + alfacalcidol 0.25 ug/bid + tibolone 1.25 mg/d orally and 33 women in group C managed by osteoform 1000 mg/d + alfacalcidol 0.25 ug/bid + bisphosphonates 70 mg/w orally. After 48 weeks BMD on lumbar 1-4 (L1-4) and left femur were detected by X-ray. Bone alkaline phosphatase(BALP), cross linked clelopeptide of type I collagen (CTX) and 25-hydroxychole calciferol [25(OH)D3] was measured by enzyme linked immunosorbent assay (ELISA). RESULT: Seven women (6.4%, 7/109) were withdrawed form this study, including 2 cases losing follow up in group A, 3 cases stopping treatment in group B, 2 cases giving up treatment due to severe adverse effect (burning in upper abdomen) in group C. (1) Pain relieve: after 48 weeks treatment, women in 3 groups improved symptom of pain significantly, the rates of pain relieve were 85% (29/34) in group A, 92% (34/37) in group B and 94% (29/31) in group C. (2) BMD: BMD was improved significantly in women in 3 groups after treatment. BMD of L1-4 were (0.88 +/- 0.15) g/cm2 in group A, (0.89 +/- 0.18) g/cm2 in group B and (0.87 +/- 0.10) g/cm2 in group C before treatment, and converted to (0.90 +/- 0.01) g/cm2 in group A, (0.93 +/- 0.09) g/cm2 in group B and (0.91 +/- 0.11) g/cm2 in group C after treatment. BMD of left femur were (0.87 +/- 0.07) g/cm2 in group A, (0.87 +/- 0.07) g/cm2 in group B and (0.85 +/- 0.12) g/cm2 in group C before treatment and converted to (0.90 +/- 0.03) g/cm2 in group A, (0.91 +/- 0.08) g/cm2 in group B and (0.89 +/- 0.12) g/cm2 in group C after treatment. It was shown significantly different BMD between group B or C and group A (P < 0.01), however, there was no significant different BMD between group B and C (P > 0.05). (3) Index of bone metabolism: BALP were (26 +/- 6) ug/L in group A, (26 +/- 9) ug/L in group B and (28 +/- 7) ug/L in group C before treatment and converted to (22 +/- 5) ug/L in group A, (20 +/- 9) ug/L in group B and (22 +/- 8) ug/L in group C after treatment, which showed statistical difference (P < 0.05). CTX were (0.85 +/- 0.20) ng/L in group A, (0.84 +/- 0.47) ng/L in group B, and (0.88 +/- 0.11) ng/L in group C before treatment and converted to (0.81 +/- 0.19) ng/L in group A, (0.77 +/- 0.33) ng/L in group B, and (0.82 +/- 0.14) ng/L in group C after treatment, which showed statistical difference (P < 0.05). CONCLUSIONS: Those 3 regimens combination could be used in treatment of osteoporosis by decreasing bone conversion, increasing bone density, decreasing bone absorption. Regimen A was only suitable for basic therapy, the other two regimens could provide better treatment. PMID- 21029612 TI - [Effects of cryopreservation time and thawing method of human oocyte vitrification on the outcome of assisted reproduction]. AB - OBJECTIVE: To evaluate the effects on pregnancy outcome of freezing time from oocyte retrieval and thawing method for metaphaseII human oocytes vitrification. METHODS: From Mar 2007 to Mar 2009, the clinical outcome of 30 infertile women undergoing vitrified-thawing oocytes of in vitro fertilization-embryo transfer (IVF-ET) in the Reproductive Medical Center of the First Affiliated Hospital of Zhengzhou University was studied retrospectively, including 21 women with double fallopian tube obstruction and 9 women's husband azoospermia. All infertile women were divided into three groups, including 5 cases in group A (freezing between 4 and 5 hours from oocyte retrieval and conventional thawing method), 9 cases in group B (freezing within 2 hours from retrieval and conventional thawing method) and 16 cases in group C (freezing within 2 hours from retrieval and improved thawing method). The vitrified oocytes were preserved for 2 months to 1 year and thawed for Intracytoplasmic sperm injection (ICSI) and embryo transfer. The outcome of IVF and pregnancy were recorded. RESULTS: (1) The rates of oocyte survival was (65 +/- 33)% in group B and (72 +/- 23)% in group C and the rate of transfer cycle was 9/9 in group B and 16/16 in group C, which were all significantly higher than (16 +/- 17)% of oocyte survival and 1/5 of transfer cycle in group A (P = 0.001, 0.021). However, the rate of oocyte survival and transfer cycle between group B and group C did not reach statistical difference (P > 0.05). The rate of implantation and clinical pregnancy of (33 +/- 38)% and 9/16 in group C were significantly higher (4 +/- 11)% and 1/9 in group B (P = 0.033, 0.040). (2) The mean age of women in group C were (28.6 +/- 2.1) in oneself oocyte, (28.0 +/- 4.6) in donor oocyte and (28.1 +/- 3.4) in donor sperm. The rate of oocyte survival was (73 +/- 25)%, (88 +/- 10)% and (66 +/- 25)%. The rate of fertilization rate was (84.6 +/- 0.9)%, (79.3 +/- 2.0)% and (82.8 +/- 15.0)%. The rate of implantation was (20.0 +/- 44.7)%, (33.0 +/- 0.1)%, (41.6 +/- 41.7)%. The rate of clinical pregnancy was 1/5 in oneself cycles, 3/3 in donor oocyte cycles, 5/8 banked donor sperm cycles in group C. All above clinical parameters were not statistically different (P > 0.05). (3) In group A, one women underwent IVF-ET and no clinical pregnancy was observed. One women pregnancy was terminated at two months in group B. The clinical pregnancies rate of group C was 9/16, late abortion occurred in 1 woman, the other 8 women underwent term pregnancy, including 5 male infants and 4 female infants. All of infants showed normal Karyotype. Live-birth rates per warmed oocyte was 5.9%(8/135). The mean gestational weeks and birth weight of the infants were (39.4 +/- 0.9) weeks and (3574 +/- 569) g, respectively. CONCLUSIONS: Embryo quality and clinical outcome of thawing cycles could be significantly improved when oocyte vitrification was performed within 2 hours from oocyte retrieval and improved thawing method. PMID- 21029613 TI - [A multi-center study to evaluate the dynamic changes of uterine artery and umbilical artery flow in a normal pregnancy and hypertensive disorders in pregnancy]. AB - OBJECTIVE: To investigate the dynamic changes of uterine artery and umbilical artery in the first, second, and third trimester of normal pregnancy and hypertensive disorders in pregnancy (HDP). METHODS: A multi-center prospective study was conducted on 1098 women with normal singleton pregnancies at the first prenatal visit in the Second West China Hospital of Sichuan University, First Affiliated Hospital with Nanjing Medical University, Beijing Obstetrics and Gynecology Hospital Affiliated to Capital Medical University, Wuhan Union Hospital Affiliated to Medical School of Huazhong University of Science and Technology and Renji Hospital Affiliated to Medical School of Shanghai Jiao Tong University from April 2005 to July 2006, with the average age of (28.3 +/- 3.3). The pulsatility indices (PI), resistance indices (RI) and systolic to diastolic velocity ratios (S/D) of uterine artery and umbilical artery were measured for all subjects in the first (10th-14th gestational weeks), second (20th-26th gestational weeks) and third trimester (30th-36th gestational weeks), respectively. In this longitudinal study, women who developed HDP were classified into HDP group, and the rest into normal pregnancy group. RESULTS: (1) Among the 1098 pregnant women, 44 developed HDP during the index pregnancy, including 20 gestational hypertension, 15 mild pre-eclampsia and 9 severe pre-eclampsia, giving an incidence of 4.17%, and the rest 1054 were normal until delivery. (2) In the normal pregnancy group, the RI, PI and S/D of uterine artery were decreased with the progress of pregnancy (RI: 0.64, 0.57, 0.50; PI: 1.24, 0.98, 0.80; S/D: 3.26, 2.58, 2.20; P < 0.01). However, the above indices showed an increasing trend with the increase of gestations in the HDP group (RI: 0.55, 0.67, 0.64; PI: 1.22, 1.36, 1.20; S/D: 3.18, 3.41, 3.05; P < 0.01). In the second and third trimester, the RI, PI and S/D of uterine artery in the HDP group were higher than those in the normal pregnancy group (P < 0.01). (3) In the normal pregnancy group, the RI, PI and S/D of the umbilical artery decreased from the second to the third trimester (RI: 0.71 and 0.58; PI: 1.16 and 0.87; S/D: 3.58 and 2.48; P < 0.01). However, no significant difference was found in the RI, PI and S/D value of umbilical artery in the second and third trimester between the normal and HDP group (RI: 0.71 and 0.63; PI: 1.20 and 0.95; S/D: 3.71 and 2.69; P > 0.05, respectively), despite the decreasing trend in the HDP group. CONCLUSIONS: In uncomplicated pregnancies, the blood flow resistance of uterine artery decreases and the end-diastolic blood flow of uterine artery increases with the progress of pregnancy. However, in pregnant women with HDP, the blood flow resistance of uterine artery increases significantly with the increase of gestations which shows significant difference to that in normal pregnancies. The blood flow resistance of umbilical artery decreases in both normal and HDP pregnant women with the increasing gestational age. PMID- 21029614 TI - [Characteristics and trends of surgical management on endometriosis: a review of cases from Peking Union Medical College Hospital from 1983 to 2009]. AB - OBJECTIVE: To investigate the characteristics and trends of surgical management on endometriosis in Peking Union Medical College Hospital From 1983 to 2009. METHODS: The medical documents of patients with endometriosis diagnosed by surgical pathology were studied retrospectively in Peking Union Medical College Hospital (PUMCH). The ratio of different surgical approaches (laparoscopic and laparotomic surgery) and surgical categories (conservative, semi-radical or radical surgery) were compared in all the cases with endometriosis to investigated alterations trends of approaches and methods of surgery. RESULTS: Totally integrated records of 13 972 patients underwent surgeries on endometriosis were reviewed and consisted of 24.974% (13,972/55,945) of all gynecologic surgeries. 59.490% of cases (8312/13,972) were treated by laparoscopic approach, which were significantly higher than the rate of 37.700% (15,824/41,973) of laparoscopic approaches in the other gynecologic diseases (P < 0.01). The proportion of laparoscopic surgeries in all endometriosis surgery was 67.31% (947/1407) between 2005 and 2009, which were significantly higher than 55.98% (510/911) of laparoscopic surgeries between 2000 and 2004 (P < 0.01). Conservative surgery (i.e., with uterus and ovaries intact) consisted of 64.014% (8663/13,533) of endometriosis surgeries. The proportion of conservative surgeries was 66.24% (4176/6304) between 2005 and 2009. The proportion of laparoscopic approaches consisted of 81.10% (7026/8663) of conservative surgeries and 26.30% (1281/4870) of semi-radical or radical surgeries (P < 0.01). The average number of annual surgeries, the average number of annual laparoscopic surgeries and its proportion in endometriosis, and the average number of annual conservative surgeries and its proportion in pelvic endometriosis between 2005 - 2009 were all increased significantly than those at range of 1983 to 1999 and 2000 to 2004. The rate of severe complication 0.351% (49/13,972) was observed in all endometriosis surgeries. CONCLUSION: Surgery was the major treatment of endometriosis in PUMCH, laparoscopic surgery was the major approach and conservative surgery was the major surgery type. PMID- 21029615 TI - [Clonal analysis of endometriotic lesions using human androgen receptor gene]. AB - OBJECTIVE: To investigate characteristics of endometriotic lesions clone with various pathological subtypes by analyzing the polymorphism of X chromosome linked human androgen receptor allele (HUMARA). METHODS: Eight frozen tissues of endometriotic leisons were collected from 6 patients who received laparotomy or laparoscopy surgery in Peking Union Medical College Hospital from Nov. 2008 to Jun. 2009. Fifty specimens of epithelial cells from single endometrial glands were isolated and collected from endometriotic lesions by using laser capture microdissection. HUMARA was applied as the gene marker of clonal analysis. Nested polymerase chain reaction, double-enzyme digestion reaction with two methylation sensitive restriction endonuclease (Hha I and Hpa II), and the automated gene sequencing technique were utilized in this study to evaluate the characteristics of endometriotic lesions clone. RESULTS: Of 50 specimens of isolated glands, 34 were informative for clonal analysis, and all of which showed monoclonality. Of 3 ovarian endometriotic tissues, one tissue of HUMARA showed unuseful information, the other 2 ovarian endometriotic tissues respectively had 4 and 7 informative specimens of gland epithelial cells, and all of the glands from each tissue showed uniform clonal pattern. Two peritoneal endometriotic tissues had 1 and 5 informative specimens from individual glands, respectively; and the clonal patterns in 5 glands from the single lesion were divergent. Two abdominal wall endometriotic tissues had 7 and 6 informative specimens, respectively; and variable clonal patterns were seen in different glands from each lesion. One deep infiltrating endometriotic lesion had 4 informative specimens of isolated glands, and all of them showed unique clonal pattern. The disparate clonal patterns were found in endometriotic lesions with variable pathological subtypes, even arising from the same patient. CONCLUSIONS: The epithelial cells from individual endometriotic gland showed monoclonality, and different glands from the same endometriotic lesion might show divergent patterns. PMID- 21029616 TI - [Relationship between cathepsin L and invasion and metastasis of ovarian carcinoma cells]. AB - OBJECTIVE: To clone cathepsin L (CTSL) gene and construct the eukaryotic expression plasmid pcDNA3.1-CTSL and study the relationship between CTSL and invasion and metastasis in ovarian cancer cells in vitro. METHODS: The total RNA was extracted from the ovarian cancer tissue and the intact cDNA of CTSL was applied by reverse transcription (RT)-PCR. The product of RT-PCR was cloned to pMD18-T vector, and subcloned to pcDNA3.1 vector. It was tested by the enzymation and DNA sequencing. The eukaryotic expression plasmid of CTSL was introduced into HO8910 cells by liposome transfection reagent. RT-PCR was used to confirm the recombinant plasmid DNA integrated with the genomic DNA of HO8910 cells. Western blot was used to confirm the CTSL protein expression in positive clones cells. The cell growth curves, clonogenicity efficiency were observed. The cell cycles were measured by flow cytometer. The ability of invasion, metastasis and adhesion of ovarian cancer cells were detected by the matrigel invasion assay, transwell migration assay and adhesion assay, respectively. RESULTS: The results from restrictive enzyme analysis and sequencing showed that the CTSL gene was successfully inserted into pcDNA3.1. Result from RT-PCR and western blot showed that the ovarian cancer cells which transfected by recombinant plasmid could express CTSL gene and protein. There was no difference between HO8910-CTSL and HO8910-pcDNA3.1 cells in proliferation and adhesion ability (0.16 +/- 0.04 versus 0.19 +/- 0.04) of the cells (P > 0.05). There was difference between HO8910-CTSL and HO8910-pcDNA3.1 cells in matrigel invasion ability (0.34 +/- 0.18 versus 0.17 +/- 0.04) and metastasis ability (1.252 +/- 0.114 versus 0.486 +/- 0.027) of cancer (all P < 0.05). CONCLUSION: CTSL maybe increase the ability of invasion and metastasis of ovarian cancer cells in vitro, which may be a molecular target of blocking invasion and metastasis of ovarian cancer. PMID- 21029617 TI - [Therapeutic effects of B and T lymphocyte attenuator extracellular domain and heat shock protein 70 antigen peptide on cervical cancer in mouse model]. AB - OBJECTIVE: To investigate the synergistic therapy effects of B and T lymphocyte attenuator (BTLA) extracellular domain in combination with heat shock protein 70 (HSP70)-TC-1 antigen peptide complex on the mouse model of cervical cancer and the related immunological mechanisms. METHODS: (1) Detecting the BTLA and herpesvirus entry mediator (HVEM) gene expression in the tumor microenvironment after C57BL/6 mice were inoculated with TC-1 tumor cells by realtime PCR; BTLA, HVEM expression on tumor infiltrating lymphocytes cell surface were detected by flow cytometry (fluorescence intensity). (2) According to different treatments, tumor-bearing mice were divided into 5 groups, which was injected with pcDNA3.1 (empty vector plasmid as control), psBTLA (vector plasmid which expresses BTLA extracellular domain), HSP70 (HSP70-TC-1 cell peptide complex), HSP70 + pcDNA3.1 or HSP70 + psBTLA, respectively. The weight of tumor was recorded. The expression of immunoregulatory genes in tumor microenvironment were detected. The change of lymphocyte amount and cytotoxicity were detected too; lymphocyte proliferation activity was measured by tritium thymidine incorporation assay; the concentration of interleukin (IL)2 and interferon-gamma (IFN-gamma) in supernatants of spleen lymphocyte were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: (1) BTLA gene expression was gradually increased after tumor cells inoculation. The highest expression level was 2.83 +/- 0.35 at 14th day, which had statistical significance difference with the 7th day expression of 1.66 +/- 0.25 (P < 0.05). While HVEM mRNA expression did not change significantly (P > 0.05). The 7th and 14th day after TC-1 cells inoculation, the average fluorescence intensity of BTLA expression on the surface of tumor infiltrating lymphocytes was 33.5 and 51.8, respectively, in which there was statistically significant difference (P < 0.05); while the difference of HVEM expression was not statistically significant (57.2 vs 49.3, P > 0.05). (2) The 28th day after inoculation, tumor inhibition rate of HSP70 + psBTLA group was 88%, which was significantly higher than other treatment groups (P < 0.05). The 28th day after TC-1 cells inoculation, combination therapy not only promoted IFN-gamma and IL-2 gene (3.12 +/- 0.71, 3.20 +/- 0.62) expression but also reduced transforming growth factor-beta (TGF-beta), Foxp3 and IL-10 expression (0.25 +/- 0.03, 0.19 +/- 0.03, 0.31 +/- 0.04; P < 0.05). It also promoted CD8(+) T lymphocyte infiltration (52 +/- 6)/high power field, cytotoxicity (65.5 +/- 2.4)%, proliferation (15.0 * 103 cpm) and cytokine IL-2, IFN-gamma secretion (824 +/- 51), (1096 +/- 112) pg/ml, which were all significantly higher than other groups (P < 0.05). CONCLUSION: The effect of immunotherapy on tumor can be augmented by the combination of psBTLA which expresses extracellular domain of BTLA and HSP70-TC-1 tumor antigen peptide complex, which could improve the expression of the related immunoregulatory genes to establish a much better microenvironment in favor of anti-tumor immune response against the mice model of the cervix carcinoma. PMID- 21029619 TI - [Application of new pattern drug-eluting stents in clinic]. PMID- 21029618 TI - [Effects of lanthanum chloride on proliferation and migration of human cervical cancer cell line HeLa cells]. AB - OBJECTIVE: To investigate the effects of lanthanum chloride on proliferation and migration activity of human cervical cancer cells in vitro which may be a new anti-cervical cancer drug and provide experimental data for cervical cancer treatment. METHODS: HeLa cells cultured in vitro were divided into two groups: experimental group and control group. In experimental group, the cells were respectively treated with lanthanum chloride at different concentrations, 5, 50 and 100 umol/L, while the cells in the control group were not treated with lanthanum chloride. The cell growth was observed by inverted microscope and the morphology changes of the cells were observed by the laser scanning confocal microscope (LSCM). Proliferation of HeLa cells in the two groups was detected by methyl thiazolyl tetrazolium (MTT) test; apoptosis rate was analyzed by flow cytometry (FCM). Cell migration test was applied to observe the effect of lanthanum chloride on migration. Reverse transcription (RT)-PCR was employed to evaluate the effects of lanthanum chloride on proliferation gene (cyclinD1), anti apoptosis gene (zinc finger protein A20) and migration-related gene (matrix metalloproteinase 9, MMP-9). RESULTS: The status of cell growth was observed under the inverted microscope: with the increased of the lanthanum chloride concentrations, the cell density of reduced, the granule in cytoplasm increased, color intensifying and intercellular space enlarged; some cells became rounding and dead, floating in the culture media; the exfoliated cells increased gradually in the experimental groups. While In the control group, the cells grew adherently, with clear morphology and plump cytoplasm, and adjacent cell grew in lamellar. Observed with LSCM: the nuclear chromatin condensated and marginated with the volume of nuclear decreased in experimental groups. With the increase of the lanthanum chloride concentrations, nuclei in the experimental groups became pyknotic and then underwent karyorrhexis. However, the nuclear of the cells in control group were inact. The growth inhibition rates of lanthanum chloride groups (5, 50, 100 umol/L) were 24%, 51% and 78%, respectively, in which each was significantly higher than that of the control group (P < 0.05); the apoptosis rates of lanthanum chloride group were (4.91 +/- 0.39)%, (7.30 +/- 0.71)% and (13.48 +/- 0.92)%, respectively, which were all significantly higher than that of the control group [(0.89 +/- 0.11)%, P < 0.01]. The migration ability of the cells was also decreased by the treatment of lanthanum chloride, the number of migrated cells in lanthanum chloride groups were 22.2 +/- 4.3, 12.0 +/- 3.2 and 7.8 +/- 2.6 respectively, which were all significantly lower than that of the control group (41.2 +/- 5.4, P < 0.01). The expression of genes of cyclinD1, A20 and MMP-9, were all decreased by the treatment of lanthanum chloride in a dose dependent manner. CONCLUSION: Lanthanum chloride can inhibit the proliferation and migration of cervical cancer cells, and induce apoptosis by down-regulating cyclinD1, A20, and MMP-9 expressions in vitro. PMID- 21029620 TI - [Vascular medicine:vascular health evaluation and vascular disease prevention and medication]. PMID- 21029621 TI - [Gender-based analyses of intervention outcome in non-ST segment elevation acute coronary syndrome]. AB - OBJECTIVE: To investigate the impact of gender on outcomes in patients with non ST segment elevation acute coronary syndrome undergoing intervention treatment. METHODS: In a multi-center randomized trial, the patients diagnosed as non-ST segment elevation acute coronary syndrome were randomly assigned to undergo early intervention (coronary angiography <= 24 h after randomization) or delayed intervention (coronary angiography >= 36 h after randomization). The primary outcome was a composite of death, myocardial infarction or stroke at 180 days. The secondary outcomes were death, myocardial infarction, refractory ischemia, stroke or revascularization at 180 days. RESULTS: Among 815 patients (545 males, 270 females), the incidences of primary and secondary outcome were equivalent for both genders (P > 0.05). Males of the early intervention group had a greater incidence of the primary outcome (7.1% vs 14.8%, P = 0.00). The secondary outcome was a composite of death, myocardial infarction or refractory ischemia occurring in 12.5% of males in early intervention group and 21.2% in delayed intervention group. Significant difference existed (P = 0.00). The incidence of another secondary outcome as a composite of death, myocardial infarction, refractory ischemia, stroke or revascularization was equivalent for males in early intervention group and delayed intervention group (26.8% vs 32.4%, P > 0.05). The incidences of primary outcome (12.6% vs 14.3%, P > 0.05) and secondary outcome (18.5% vs 23.5% P > 0.05; 28.5% vs 27.7% P > 0.05) were equivalent for females in early intervention group and delayed intervention group (P > 0.05). CONCLUSION: Patients with non-ST segment elevation acute coronary syndrome undergoing intervention demonstrate no significant gender differences in efficacy and safety. Early intervention reduces the rate of myocardial infarction for males, but it is not superior to delayed intervention for females. PMID- 21029622 TI - [Therapeutic effect and safety of drug eluting stent for patients with acute ST elevation anterior wall myocardial infarction by left anterior descending artery occluded abruptly]. AB - OBJECTIVE: To assess the therapeutic effect and safety of drug eluting stent for the patients with anterior wall myocardial infarction by left anterior descending artery occluded abruptly. METHODS: From January 2004 to December 2008, 302 patients with anterior wall myocardial infarction in 12 hours from chest pain to treatment were treated. But only 189 patients were recruited and randomly divided into drug eluting stent group (n = 95) and bare metal stent group (n = 94). The occurrence of cardiac death, stent thrombosis, reinfarction, target vessel revascularization and re-hospitalization because of heart function failure was compared. RESULTS: There was no difference in cardiac death [3/95 (3%) vs 7/94 (7%), P = 0.206], reinfarction [1/95 (1%) vs 5/94 (5%), P = 0.112] and re hospitalization because of heart function failure [8 (8%) vs 5 (5%), P = 0.434]. Compared with those in bare metal stent group, the patients in drug eluting stent group has a lower rate of target vessel revascularization [2 (2%) vs 13 (14%), P = 0.009] and composite therapeutic effect endpoints [12 (13%) vs 25 (27%), P = 0.011]. There was no difference in safety endpoint or stent thrombosis [1 (1%) vs 4 (4%), P = 0.204]. CONCLUSION: In patients with anterior wall myocardial infarction by left anterior descending artery occluded abruptly, drug eluting stent decreases the rate of target vessel revascularization. But it has no increased stent thrombosis. PMID- 21029623 TI - [Long-term follow-up after drug-eluting stents for patients with ST-segment elevation myocardial infarction: a single center study]. AB - OBJECTIVE: To evaluate the long-term efficacy and safety of DES in the setting of primary PCI in our single center. METHODS: From September 2004 to November 2008, 464 patients undergoing primary PCI for STEMI were included at the 28th Division in Beijing Anzhen Hospital. The adverse events were compared among different types of DES. RESULTS: The major adverse cardiac events [MACE, including sudden cardiac death, stent thrombosis, target lesion revascularization (TLR), target vessel revascularization (TVR), reinfarction and coronary artery bypass graft], all-cause death, major bleeding, anti-platelet therapy and secondary prevention of coronary heart disease of different types of DES were no significant differences. The cumulative incidence of MACE and stent thrombosis were 9.3% and 1.1% respectively, different types of DES were 9.4%, 5.1%, 5.9%, 6.6% (P = 0.483) and 3.1%, 0.0%, 0.0%, 0.0% (P = 0.092) respectively. The patients in the DES group had longer duration of dual antiplatelet therapy (average 16.2 +/- 6.7 months). No major bleeding occurred in all patients with the long-term and low dose aspirin (100 mg). CONCLUSIONS: Different types of DES have the same results in the setting of primary PCI, and were long-term safe and effective with a reasonable strategy for anti-platelet therapy and secondary prevention. PMID- 21029624 TI - [Minimally invasive low-collar incision in near total thyroidectomy]. AB - OBJECTIVE: To explore the clinical feasibility and features of adopting a low collar arc-shaped incision for minimally invasive near total thyroidectomy. METHODS: From April 1998 to March 2007, the procedure was accepted by 53 patients with thyroidal nodules, including nodular goiter (n = 34), thyroid adenoma (n = 12) and thyroid carcinoma (n = 7). Near total thyroidectomy was performed through a 2 - 4 cm low-collar horizontal skin incision by conventional instrumentation. RESULTS: The incision yielded excellent cosmetic results because the small and lower incisions were completely hidden by clothing collar. The recurrent laryngeal nerve and parathyroid glands were easily identified and preserved. The mean operation time was 62.2 minutes (range: 58 - 112). No complication occurred. The mean bleeding amount was 25 ml (min: 10, max: 100). The drainage was extracted at Day 2 or 3 postoperatively. The mean postoperative stay was 7.6 days (range: 7 - 12) while the post-operative follow-up 2 months to 9 years. CONCLUSION: Such technique is feasible, safe, minimally invasive, less time consuming and cosmetically ideal. It is suitable for young and middle-aged women. PMID- 21029625 TI - [Combined palliative procedures for cyanotic congenital heart defects with intractable hypoplasia of pulmonary arteries]. AB - OBJECTIVE: To explore the clinical experiences of combined palliative procedures for cyanotic congenital heart defects with intractable hypoplasia of pulmonary arteries. METHODS: From August 2001 to September 2009, 31 patients with cyanotic congenital heart defects and intractable hypoplasia of pulmonary arteries underwent surgical procedures. Among them, 26 patients were pulmonary atresia with ventricular septal defect and the other 5 cases complicated congenital heart defects with pulmonary stenosis. Different kinds of palliative procedures were performed according to the morphology of right and left pulmonary arteries in every patient. If the pulmonary artery was well developed, Glenn procedure was performed. Modified Blalock-Taussig or Waterston shunt was performed if pulmonary arteries had hypoplasia. If the pulmonary arteries were of severe hypoplasia, Melbourne shunt was performed. Systemic-pulmonary artery shunts were performed bilaterally in 23 cases. Systemic-pulmonary shunt was performed in one side and Glenn procedure contralaterally in 8 cases. RESULTS: There was one early death because of cardiac arrest. The number of patients suffered from low cardiac output syndrome, perfusion lung and pulmonary infection postoperatively was 5, 3 and 2, respectively. Systemic-pulmonary shunts were reperformed after the original operation in 3 cases because of occlusion of conduits. The mean follow up time was 25 +/- 16 months (6 - 72 months). Left pulmonary index (8.1 +/- 3.7 vs 14.9 +/- 6.2), right pulmonary index (12.7 +/- 8.1 vs 17.7 +/- 7.8) and pulmonary index (20.9 +/- 9.4 vs 32.6 +/- 11.7) increased significantly (all P < 0.001). The pulmonary diameter increased significantly after modified Blalock Taussig shunt (5.5 +/- 1.0 vs 7.0 +/- 2.0), modified Waterston shunt (5.7 +/- 4.0 vs 9.2 +/- 3.6) and melbourne shunt (2.2 +/- 0.4 vs 7.4 +/- 2.5) (all P < 0.05). Bilateral pulmonary arteries developed well compared with that of preoperative condition. Hemoglobin decreased from (194 +/- 27) g/L to (174 +/- 24) g/L (P < 0.05) and peripheral oxygen saturation increased from (65 +/- 11)% to (84 +/- 6)% (P < 0.001). During the follow-up ultimate complete repair were performed in 3 cases and one patients underwent Glenn procedure. CONCLUSIONS: The procedures should be considered for hypoplasia of pulmonary arteries in cyanotic congenital heart defects. Combined palliative operation is an adequate therapy. PMID- 21029626 TI - [Correlation between expression of excision repair cross-complementing 1 and cisplatin sensitivity in non-small cell lung cancer]. AB - OBJECTIVE: To investigate the correlation between excision repair cross complementing 1 (ERCC1) expression and cisplatin sensitivity in non-small cell lung cancer (NSCLC). METHODS: A total of 168 NSCLC patients were selected from our hospital from January 2005 to December 2007. The expression of ERCC1 protein was analyzed by immunohistochemistry and ERCC1 mRNA tested by RT-PCR. Analyses were performed to determine the correlation between expression of ERCC1 and chemotherapeutic sensitivity in NSCLC. RESULTS: A positive expression of ERCC1 protein was found in 99 (58.93%) patients. The expression of ERCC1 had no correlation with gender, age, stage and pathological types (P > 0.05). Among all patients, 133 were followed up for about 3-5 years and 91 cases belonged to the responding group. Three cases with stage Ia-Ib underwent only operation without chemotherapy. And 76 (58.46%) patients were positive for ERCC1 expression in 130 cases. In the responding group, 38 (43.18%) cases had a positive expression of ERCC1 and 50 (56.82%)cases a negative expression of ERCC1. In the non-responding group, 37 (88.10%)cases had a positive expression of ERCC1 and 5 (11.90%) cases a negative expression of ERCC1. The expression of ERCC1 decreased in the responding group versus the non-responding group (chi(2) = 23.50, P < 0.01). The expressions of ERCC1 mRNA were (0.624 +/- 0.275) and (2.758 +/- 0.771) in the responding and non-responding groups respectively (t = 11.54, P = 0.013). CONCLUSION: An elevated expression of ERCC1 is an important factor for cisplatin insensitivity in NSCLC. It may provide an useful reference for designing individualized chemotherapeutic regimens for NSCLC patients. PMID- 21029627 TI - [Clinical features of 9 patients with X-linked adrenal hypoplasia congenita caused by DAX1/NR0B1 gene mutations]. AB - OBJECTIVE: To study the clinical features of 9 patients with X-linked adrenal hypoplasia congenita (AHC) by gene sequencing so as to provide diagnostic rationales. METHODS: The patients were 9 cases of X-linked AHC treated at our hospital from July 2007 to June 2009. The clinical manifestations were analyzed. The blood biochemistry tests and the hormone examinations including luteinizing hormone-releasing hormone (LHRH) stimulation tests and human chorionic gonadotropin (HCG) stimulation tests were conducted to evaluate the functions of gonads. And CT scans of adrenal glands and gene tests of DAX1/NR0B1 were performed. RESULTS: Nine AHC patients from 8 families were studied. All patients had DAX1/NR0B1 gene mutations. The main clinical features were: (1) some patients (3 families) had a family history of X-linked recessive inheritance; (2) the ages of onset were all below 10 years old (from 2 month after birth to 9 years old) and ages of being treated at our hospital were from 15 to 34 years old; (3) all patients had adrenocortical hypofunctions, but clinical situations were different, most of them had pigmentation (n = 9), nausea and vomiting (n = 8), hypotension (n = 6), Addisonian crisis (n = 4). Others were debility, hypoglycemia and cold susceptibility. Laboratory tests indicated that all patients had hyponatremia at the onset and higher blood adrenocorticotropic hormone level, lower blood 17-hydroxyprogesterone level compared to normal controls; (4) none of the patients had puberty and there was no responses to LHRH stimulation tests, 3 of them had normal responses to HCG stimulation tests; (5) small bilateral adrenal glands were displayed on CT scans. CONCLUSIONS: The main clinical features of X-linked AHC are adrenocortical hypofunction and hypogonadotropic hypogonadism. But the phenotypes vary greatly in different patients. So male children with adrenal cortical hypofunction should be suspected of X-linked AHC and DAX1/NR0B1 gene tests should be performed. The sexual development of the patients also should be followed up. PMID- 21029628 TI - [Combined therapy of advanced adrenal cortical adenocarcinoma]. AB - OBJECTIVE: To analyze the clinical efficacy of combined therapy in the treatment of advanced adrenal cortical adenocarcinoma. METHODS: The clinical data of 12 cases with advanced adrenal cortical adenocarcinoma at our hospital from 1986 - 2006 were analyzed. And the relevant literatures were reviewed. RESULTS: Eleven patients underwent operation to remove primary lesions. Only 1 case received a biopsy. All cases were treated with chemotherapy or chemotherapy pulse post operative radiotherapy. Pathological diagnosis was all of adrenal cortical adenocarcinoma. According to the staging criteria of Jacques and Brennan, all 12 cases were of IV stage. The follow-up duration was 6 - 40 months. According to evaluation criterion of chemotherapeutic effect by WHO in 1987, the results were: CR (complete remission) (n = 0), PR (partial remission) (n = 7), SD (stable disease) (n = 3) and PD (progressive disease) (n = 2). The effective rate was 58.3% (7/12). The median survival time was 14 months and median progression-free survival time 9 months. CONCLUSION: Combined therapy of adrenal cortical adenocarcinoma is effective to prolong the patient lifespan. Radiotherapy offers partial symptomatic relief for those with osseous metastasis. Making an early diagnosis and offering a novel therapy yield a better outcome. PMID- 21029629 TI - [Anti-tumor efficacy of interventional chemotherapy with liposomal doxorubicin for hepatic metastasis of pancreatic cancer in nude mouse model]. AB - OBJECTIVE: To investigate the anti-tumor effect of interventional chemotherapy with liposome doxorubicin for hepatic metastasis of pancreatic tumor in nude mice. METHODS: After the establishment of hepatic metastatic model of pancreatic tumor, the nude mice received various formulations via a spleen injection to imitate the interventional chemotherapy. In each of two following experiments, 42 nude mice were randomly divided into 6 groups. They received liposomal doxorubicin (including high, intermittent and low-dose), free doxorubicin, gemcitabine plus cisplatin and control respectively. In the first experiment, the doses were 6, 3, 1.5, 3, 3 mg/kg and 100 ul 10% glucose for each group respectively. And in the second experiment, 9, 6, 3, 6, 6 mg/kg, and 100 ul 10% glucose respectively. The efficacies of interventional injection of liposomal doxorubicin with different doses were examined in terms of tumor growth retardation for the hepatic metastatic foci of pancreatic tumor. RESULTS: In the first experiment, the difference of median hepatic tumor volume was significant among the three groups of mice receiving liposomal doxorubicin with incremental doses in a dose-dependent manner [high dose: (3 +/- 1) mm(3), middle dose: (55 +/ 18) mm(3), low dose: (90 +/- 23) mm(3), P < 0.05]. The liposomal doxorubicin led to a substantial delay of tumor growth as compared to the free drug or gemcitabine plus cisplatin at the same dose (both P < 0.05). In addition, all animals were well-tolerated with no obvious acute toxicity. In the second experiment, significant difference was obtained for the mice injected with different doses of liposomal doxorubicin [(11 +/- 4) mm(3), (13 +/- 4) mm(3), (50 +/- 18) mm(3), P < 0.05]. It was correlated with tumor growth delay. The mice administered with either 9 mg/kg or 6 mg/kg were more efficacious to retard tumor growth than those given 3 mg/kg (P < 0.05). Despite its enhanced effectiveness as compared to mice in gemcitabine plus cisplatin group (P < 0.05), the liposomal doxorubicin at a dose of 6 mg/kg resulted in a marginally delayed tumor growth compared to those of free doxorubicin at the same dose (P > 0.05). No evident acute toxic response was observed for each group of mice receiving liposomal doxorubicin. In contrast, approximately half of the animals receiving either free doxorubicin or gemcitabine plus cisplatin died of toxic responses. CONCLUSION: Liposomal doxorubicin may be a potential interventional chemotherapeutic agent for hepatic metastasis of pancreatic tumor because of improved anti-tumor efficacy and reduced toxicity in comparison to free doxorubicin and gemcitabine plus cisplatin. PMID- 21029630 TI - [Construction of CYP2E1 recombinant adenovirus vector and its anti-tumor effects]. AB - OBJECTIVE: To construct the human cytochrome P-450 CYP2E1 (CYP2E1) recombinant adenovirus vector and detect its anti-tumor effects in combination with chemotherapeutic drugs so as to provide rationales for gene directed enzyme prodrug therapy (GDEPT). METHODS: CYP2E1 cDNA was cloned from human liver and a recombinant adenovirus vector constructed at a titer of 1 * 10(12) pfu/ml. Human bone marrow-derived mesenchymal stem cells (BMSCs) were separated, cultured, purified and detected. The tropism of BMSCs for cancer cells was detected by Transwell technique. These recombinant vectors were transferred into BMSCs and A375 cells and the expressions of EGFP and CYP2E1 detected by fluorescence microscope, RT-PCR and Western blot respectively. Inverted microscope, MTT and Annexin V-FITC/PI were employed to detect the anti-tumor effect of CYP2E1 recombinant adenovirus vectors in combination with chemotherapeutic prodrug dacarbazine (DTIC). RESULTS: The recombinant adenovirus vectors pAd5CMV-NpA CYP2E1 and pAd5CMV-NpA-EGFP were constructed successfully. BMSCs were successfully separated and they could migrate in vitro through a polycarbonate filter toward K562 and A375 cells in the lower chamber. Fluorescence microscope was used to detect the expression of EGFP while both RT-PCR and Western blot revealed a high expression of CYP2E1 in gene-transfected group cells. The dead cell counts of co-culture group of gene-transfected BMSCs and wild type A375 cells were significantly higher than those of the control under inverted microscope. The results of MTT showed that the growth inhibition of gene transfected group cells was increased with DTIC concentration in a concentration dependent manner. IC(50) of group BMSCs-CYP2E1 + A375 was (0.17 +/- 0.13) mmol/L, and that of the control group was (0.65 +/- 0.20) mmol/L (P < 0.01). The DTIC concentration at which BMSCs were relatively safe might be selected at 0.05 mmol/L. Annexin V-FITC/PI confirmed that the apoptosis rate of BMSCs-CYP2E1 + A375 group was significantly higher than that of the control group after a 48 hour treatment of 0.05 mmol/L DTIC (26.8 +/- 2.0 vs 8.7 +/- 1.3, P < 0.01). CONCLUSION: With an in vitro tropism for cancer cells, BMSCs transferred with CYP2E1 recombinant adenovirus vectors have anti-tumor effects probably synergistically with chemotherapeutic drugs. PMID- 21029631 TI - [Establishment of a xenograft model of human prostate cancer in mouse]. AB - OBJECTIVE: To establish the murine xenograft model of human prostate cancer by grafting tumor tissues beneath the renal capsule of intact male athymic mouse. METHODS: Fifteen SCID mice were randomly divided into 3 groups (n = 5 each). Tissue recombinants were prepared in vitro with newborn BALB/c murine seminal vesicle mesenchyme (SVM) and surgical isolated human prostate cancer tissues by using recombination technique and then grafted beneath the renal capsule of intact male athymic mouse. At Week 4 after initial implantation, grafts were harvested and tumor sizes calculated. The expressions of human specific markers CK8/18 and vimentin were evaluated by immunohistochemistry to identify the human prostatic origin in grafts. P63 protein, a basal cell marker, was detected in prostate basal membrane to identify whether it was benign or malignant tissue. And the study control was prepared by implanting prostate cancer tissues alone under the renal capsule in SCID mouse. RESULTS: Of all 78 implantation cases in 15 mice, the tumor-forming rates were 100% (39/39) and 94.1% (37/39) respectively in the recombination and prostate cancer alone grafting groups. The recombination group was shown to be more efficient in terms of tumor size and weight in comparison with the prostate cancer alone group [(9.7 +/- 3.1) vs (6.8 +/- 2.0) mm(3), (12.1 +/- 3.6) vs (8.2 +/- 2.2) ug, P < 0.01]. There was no difference in serum PSA level between two groups. Grafts were confirmed as human prostate cancer tissues with the expressions of CK8/18 and vimentin. No expression of P63 was detected. CONCLUSION: The xenograft murine model of human prostate cancer is successfully established. It contains stroma components and is particularly suitable for studying the interaction of stroma and epithelia in the in vivo progression of prostate cancer. PMID- 21029632 TI - [Up-regulation of stathmin induces growth arrest of esophageal squamous cell carcinoma EC9706 cell]. AB - OBJECTIVE: To construct a eukaryotic expression vector of stathmin gene and investigate its effect on esophageal squamous cell carcinoma (ESCC) EC9706 cell line. METHODS: Stathmin cDNA coding sequence was amplified by RT-PCR and cloned into a eukaryotic expression vector pcDNA3.1(+). EC9706 cells were transfected with this recombinant plasmid pcDNA3.1-stathmin by lipofectamine. And the stable transfectants were selected with G418 medium. Stathmin protein expression was detected with Western blot in transfected EC9706 cell lines. Morphologic change of stable transfectants was observed under microscope. The proliferation of transfected cells was measured by cell counting, MTT and in vitro formation assay of flat. Flow cytometry was used to detect the cell cycle. Nude mice were adopted to investigate the in vivo tumorigenic characteristics of the transfected cells. RESULTS: A 450 bp coding sequence of stathmin cDNA was amplified by RT-PCR and then cloned into pcDNA3.1(+) plasmid to harvest the recombinant plasmid pcDNA3.1 stathmin. The recombinant plasmid pcDNA3.1-stathmin and blank vector were transfected respectively into EC9706 cells. The up-regulated expression of stathmin protein was validated by Western blot (P < 0.01). Compared with control, EC9706 cells transfected with pcDNA3.1-stathmin appeared swollen and multi nuclear with a cell mitotic arrest; doubling generation time of pcDNA3.1-stathmin transfectants was prolonged (25 - 28 h); The in vitro cell proliferation ability and clone formation rate (34.5% +/- 6.9%) decreased, cell cleavage was blocked at G(2)/M phase (21.7% +/- 3.4%) and the oncogenicity of inoculated cells in nude mice decreased (all P < 0.01). CONCLUSIONS: The up-regulated expression of stathmin protein triggered by the recombinant plasmid pcDNA3.1-stathmin can inhibit the proliferation and oncogenicity of ESCC EC9706 cells. This molecule may be a promising therapeutic target in ESCC patients. PMID- 21029633 TI - [Molecular mechanism of norcantharidin inducing apoptosis in liver cancer cells]. AB - OBJECTIVE: To elucidate the molecular mechanism of norcantharidin (NCTD) in inducing apoptosis of liver cancer cells so as to provide basic rationales for its application in liver cancer treatment. METHODS: Liver cancer cell lines of SMMC-7721 and BEL-7402 were treated with NCTD. The cell growth inhibition was measured by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, cell death detected by trypan blue exclusion assay and apoptosis examined by Annexin V/PI staining and flow cytometry. The cleavage of caspase-9, -3 and PARP, and the expression of the anti-apoptotic Bcl-2 proteins were analyzed by Western blot. RESULTS: The MTT results showed that, after a treatment with NCTD for 24, 48 and 72 h, the IC50 of NCTD in SMMC-7721 cell line was 12, 6 and 1.6 ug/ml respectively; in BEL-7402, the IC50 10, 4 and 2 ug/ml respectively. Trypan blue exclusion assay showed that NCTD mediated substantial cell death in two cancer cell lines. Apoptosis assay showed that, after a 12 h treatment with 10 ug/ml NCTD, 27% of SMMC-7721 cells were induced to undergo apoptosis, an increment of 20% over the untreated control cells (7%); 30% of BEL-7402 cells became apoptotic, an increment of 22% over the untreated control cells (8%). Western blot analysis showed that NCTD treatment potently induced the activation of caspase-9, -3 and the cleavage of PARP, and markedly down-regulated the expression of Bcl-2, Bcl-X(L) and Mcl-1. CONCLUSION: NCTD strongly inhibits liver cancer cell growth and potently induces apoptotic cell death in two liver cancer cell lines. The strong anticancer activity of NCTD may be induced through targeting multiple Bcl-2 anti-apoptotic family members. PMID- 21029634 TI - [Effects of hypoxia on the proliferation of human bone marrow mesenchymal stem cells]. AB - OBJECTIVE: To study the effect of hypoxia on the proliferation of human bone marrow mesenchymal stem cells (hBMSCs). METHODS: The method of density gradient centrifugation was employed to isolate and culture hBMSCs. And flow cytometry (FCM) was employed to detect the cell surface marker. After establishing the experimental model of CoCl2-chemical hypoxia, MTT method and flow cytometry were applied to evaluate the proliferation and the proliferation index of hBMSCs at different time points with various CoCl2 concentrations. RESULTS: The proliferations of hBMSCs was inhibited within the first 12 hours under chemical hypoxia condition. Compared with the normal group, the hBMSCs of each CoCl2 group were remarkably proliferated 1, 2, 4 days after chemical hypoxia with CoCl2, but 300 umol/L CoCl2 group showed no significant difference (P > 0.05). 100 umol/L CoCl2 group (0.139 +/- 0.003, 0.178 +/- 0.005, 0.224 +/- 0.005) and 150 umol/L CoCl2 group (0.202 +/- 0.020, 0.224 +/- 0.019, 0.263 +/- 0.004) proliferation was significantly higher than that of the control group (0.134 +/- 0.005, 0.167 +/- 0.004, 0.206 +/- 0.005). Compared with the normal group, the hBMSCs were remarkably proliferated 24 hours after chemical hypoxia with CoCl2 concentration of 150 umol/L (all P < 0.05). At Day 6, the 100, 150 umol/L CoCl2 group (0.258 +/ 0.020, 0.264 +/- 0.008) cells was still higher than that of normal group (0.248 +/- 0.004), but the advantage gradually diminished (P < 0.05). At Day 7, the proliferative effects of hypoxia disappeared. CONCLUSION: CoCl2-induced chemical hypoxia may promote the proliferation of hBMSCs. PMID- 21029635 TI - [Application of the brain electrophysiology in schizophrenia: present aspects, progress and prospect]. PMID- 21029636 TI - [P50 sensory gating studies in schizophrenics: a systematic review]. AB - OBJECTIVE: To conduct a systematic review of P50 sensory gating studies in schizophrenics and the change between before and after treatment. METHODS: Standard search strategy for the Cochrane Review Group was performed by two review authors. Searches were made in PubMed, EMBase, Web of knowledge, PsycINFO, Cochrane Library, CNKI, Wanfang, VIP and CBMDisc databases. STROBE (strengthening the reporting of observational studies in epidemiology) was used to assess the methodological quality of the studies. RevMan 5.0.23 software was employed to conduct a Meta analysis. RESULTS: Seventy-one literatures were reviewed and 7 studies met the inclusion criteria for a Meta analysis. The meta-analysis of random effects showed that S1 amplitude was lower in the schizophrenia group than in the normal control group (P = 0.02). And S2 amplitude was significant higher in schizophrenia group than the normal control group (P = 0.001). There were no statistical significance in S1 and S2 latency between two groups (P = 0.34 and P = 0.19 respectively). P50 Ratio in schizophrenia group was significantly higher than the normal control group. And the difference was statistically significant [Z = 11.46, P < 0.00001, combined SMD = 44.18, 95%CI (36.62, 51.74)]. However the P50 difference showed no significant difference (P = 0.14). An analysis of fixed effects showed that the P50 Ratio difference was not statistically significant in schizophrenics between before and after treatment (P = 0.19). CONCLUSION: The schizophrenics have a sensory gating dysfunction. P50 Ratio is a stable and reliable indicator of sensory gating function. Antipsychotics may partly enhance P50 sensory gating in schizophrenics, but can not completely reverse the defect of P50 suppression. PMID- 21029637 TI - [N400 changes elicited by Chinese sentences in first episode schizophrenia]. AB - OBJECTIVE: To explore N400 changes elicited by Chinese sentences ending with matching (congruent) or mismatching (incongruent) words in first episode schizophrenia. METHODS: ERP (event-related potentials) component N400 were recorded by an ERP device in 56 first episode schizophrenia (FES) and 62 normal controls (NC) according to a paradigm of Chinese sentences ending with matching or mismatching words. RESULTS: (1) Latencies: compared with NC, FES showed prolonged N400 latencies in five areas at pre-treatment: in Cz. The latencies were (358 ms +/- 32 ms vs 394 ms +/- 45 ms, P < 0.01) in congruent and (410 ms +/ 29 ms vs 446 ms +/- 35 ms, P < 0.01) in incongruent situation. And so did in Fz, Pz, C3 and C4; (2) amplitudes: compared with NC, FES also showed smaller N400 amplitudes in five areas at pre-treatment. The amplitudes were (8.6 uV +/- 5.1 uV vs 5.2 uV +/- 4.6 uV, P < 0.01) in congruent and (13.4 uV +/- 6.7 uV vs 8.5 uV +/ 5.9 uV, P < 0.01) in incongruent situation. And so did in Fz, Pz, C3 and C4; (3) the prolonged N400 latencies and decreased amplitudes were negatively correlated with the patients' positive scale and total scale of PANSS. CONCLUSION: With clear priming effect in first episode schizophrenia, Chinese sentences are suitable stimuli in N400 experiment. They may be used for further study of neural mechanism and early diagnosis of schizophrenia. PMID- 21029638 TI - [Efficacy of paliperidone extended-release tablets in the improvement of social functions in schizophrenics: a randomized and controlled study]. AB - OBJECTIVE: To explore the efficacy of paliperidone extended-release tablets in the improvement of social functions in schizophrenics. METHODS: A total of 81 schizophrenics were randomly divided into study group with paliperidone extended release tablets and control group with risperidone for a 12-week treatment. They were assessed and analyzed by positive and negative symptoms scales (PANSS), social disability screening schedule (SDSS) and treatment emergent symptom scale (TESS) at baseline, 6(th) weekend and 12(th) weekend. RESULTS: In study group, the factors and total scores of PANSS in the 12(th) weekend of treatment [(12.0 +/- 2.8), (12.1 +/- 3.6), (26.2 +/- 5.0), (50.2 +/- 8.7)] were all significantly lower than those at baseline [(24.7 +/- 5.3), (23.8 +/- 3.6), (45.0 +/- 2.9), (93.5 +/- 6.8)] (t = 9.60-16.78, P < 0.05). In study group, the positive factor, negative factor and total scores of PANSS in the 12(th) weekend of treatment [(12.0 +/- 2.8), (12.1 +/- 3.6), (50.2 +/- 8.7)] were all significantly lower than those in the 6(th) weekend of treatment [(14.2 +/- 1.8), (14.6 +/- 2.4), (56.5 +/- 6.4)] (t = 2.58-4.26, P < 0.05). In the 12(th) weekend of treatment, the factors and total scores of PANSS in study group [(12.0 +/- 2.8), (12.1 +/- 3.6), (26.2 +/- 5.0), (50.2 +/- 8.7)] were all significantly lower than those in control group [(16.9 +/- 4.9), (18.7 +/- 5.3), (32.5 +/- 5.1), (68.1 +/- 13.0)] (t = -4.28--5.67, P < 0.05). In study group, the total scores of SDSS in the 12(th) weekend of treatment (5.93 +/- 2.78) were significantly lower than those at baseline (13.9 +/- 3.4) (t = 10.83, P < 0.05). In study group, the total scores of SDSS in the 12(th) weekend of treatment (5.9 +/- 2.8) were significantly lower than those in the 6(th) weekend of treatment (7.6 +/- 2.9) (t = 5.21, P < 0.05). But there was no significant improvement in control group (t = 1.88, P > 0.05). In the 12(th) weekend of treatment, the total scores of SDSS in study group (5.9 +/- 2.8) were significantly lower than those in control group (8.8 +/- 2.9) (t = -4.49, P < 0.05). No severe adverse effect was reported in either group. CONCLUSION: Paliperidone extended-release tablets are effective to improve social functions and psychiatric symptoms of schizophrenics. PMID- 21029639 TI - [Effect of obesity on nonalcoholic fatty liver disease in Chinese women with polycystic ovary syndrome]. AB - OBJECTIVE: To investigate the effect of obesity on nonalcoholic fatty liver disease (NAFLD) in women with polycystic ovary syndrome (PCOS). METHODS: The patient data were acquired from 306 women with PCOS by Rotterdam consensus criteria and 286 women selected as controls. Basal endocrine, oral glucose tolerance test (OGTT), insulin release test, lipid profile, blood pressure and body mass index (BMI) were tested. The essays of liver chemistries, B-hepatitis and c-hepatitis were performed and alcoholic liver diseases excluded. Fatty liver was diagnosed by ultrasound. RESULTS: Patients with PCOS showed a higher prevalence of NAFLD than control group (30.7% vs 17.5%), including 56 mild cases (59.6%), 34 moderate cases (36.2%) and 4 severe cases (4.2%). The prevalence of NAFLD in PCOS increased with BMI, waist hip ratio, triglyceride and HOMA-IR. The prevalence of NAFLD in abdominal obese PCOS patients was significantly higher than those with normal waist. In addition to the prevalence of insulin resistance, metabolic syndrome in PCOS women significantly increased with BMI. CONCLUSION: These findings indicate that Chinese women with PCOS have a high prevalence of NAFLD, especially in abdominal and II obese PCOS patients. The prevalence and severity of NAFLD are positively correlated with BMI. It seems that insulin resistance and metabolic abnormalities are closely associated with NAFLD in PCOS. It is essential to give a high priority to the screening and treatment of NAFLD in obese PCOS patients. PMID- 21029640 TI - [Effect of lesion length on in-stent restenosis after intracranial stenting]. AB - OBJECTIVE: To evaluate the effect of lesion length on in-stent restenosis (ISR) after intracranial stenting. METHODS: Between March 2004 and September 2009, 65 patients with symptomatic intracranial arterial stenosis were successfully implanted with single bare metal balloon-mounted stent. All received a conventional angiographic follow-up. The patients were divided into three groups according to lesion length: short lesions (< 5 mm), medium lesions (5-10 mm) and long lesions (> 10 mm). ISR was defined as > 50% stenosis within stent or absolute luminal loss > 20%. The influence of different lesion lengths on ISR was evaluated. Furthermore, the independent predictive factors for ISR were selected. RESULTS: There were short lesions (n = 28), medium lesions (n = 29) and long lesions (n = 8). The median interval of angiographic follow-up was 7 months with a range of 5-30 months. Of 65 patients, 19 (29.2%) had ISR. The ISR rates were 14.3%, 37.9% and 50% in short lesions, medium lesions and long lesions respectively (P = 0.045). Multivariate Cox regression analysis showed that lesion length (HR = 1.210; 95%CI = 1.011-1.446; P = 0.037) and diabetes (HR = 2.630; 95%CI = 1.032-6.705; P = 0.043) were associated with ISR. CONCLUSION: Lesion length and diabetes are two independent predictors for ISR after intracranial stenting. PMID- 21029641 TI - [Effects of Shenfu injection on coagulation function, D-dimer and plasma p selectin in elderly patients during total hip replacement surgery]. AB - OBJECTIVE: To investigate the effects of SF injection on coagulation function, p selectin and D-dimer concentrations in plasma of elderly patients undergoing total hip replacement (THR). METHODS: Twenty-four ASA II/III patients aged 65 to 85 were divided equally into two groups (n = 12). In Group S, SF injection was administered by peripheral intravenous infusion at initially 0.2 ml/kg and then 0.8 ml (kg/h) until the end of operations. In Group N, normal saline was administered similarly. All the patients were given patient-controlled epidural analgesia (PCEA) after operations. Blood samples were taken before operations (T(0)), immediately post-operation (T(1)) and 24 h post-operation to detect the levels of p-selectin, D-dimer, blood platelet count and clotting time at all time points. RESULTS: The concentrations of p-selectin and D-dimer in Group N increased at T(1) and T(2) while those in Group S decreased at T(1) (P < 0.05). Compared with Group N, they were significantly lower in Group S (P < 0.05). There was no significant difference at T(2) between two groups. CONCLUSION: The plasma concentrations of p-selectin and D-dimer increase obviously in elderly THR patients. SF injection can decrease the plasma concentrations of p-selectin and D dimer in patients during surgery. Thus it may protect the vascular endothelial cells and attenuate the activation of platelet and fibrinolysis. PMID- 21029642 TI - [The feasibility of Supreme laryngeal mask airway in gynecological laparoscopy surgery]. AB - OBJECTIVE: To explore the safety, efficacy and side effect of Supreme laryngeal mask airway (LMA) used in gynecological laparoscopy. METHODS: From Oct. 2009 to Apr. 2010 in First Hospital of Peking University, 125 patients undergoing general anesthesia for elective gynecological laparoscopy were reviewed, 69 of which were dealt with Supreme LMA (S) and 56 with endotracheal tube (T). After anesthesia induction, changes of HR and MAP were observed during intubation and extubation. The peak inspiratory airway pressure (P(peak)) and P(ET)CO(2) were monitored. Relevant perioperative side effects were recorded. RESULTS: HR and MAP in group T were increased right after intubation and during extubation (P < 0.05), which were significantly decreased in group S (P < 0.01). P(peak) and P(ET)CO(2) were comparable in the two groups at all the time points (P > 0.05). There was no body movement or coughing at the time of intubation. Group S had less incidence of body movement, coughing and sore throat than group T during extubation (P < 0.05). CONCLUSION: Supreme LMA can provide the same safe and effective ventilation as intubation and less stress response and side effects in gynecological laparoscopy. PMID- 21029643 TI - [Evaluation of right ventricle function by tissue Doppler imaging in patients with acute organophosphate poisoning]. AB - OBJECTIVE: To evaluate the right ventricular functions of patients with acute organophosphate poisoning patient (AOPP) by measuring the velocities of tricuspid annular motion through Doppler tissue imaging (DTI). METHODS: Tissue Doppler velocity mode was employed to observe tricuspid annulus movement in 78 AOPP patients and 32 healthy adults. After tricuspid annular pulsed-wave rate of E/A were measured by traditional echocardiographic, the peak values of tricuspid annular early diastolic velocity (E(m)) and late diastolic velocity (A(m)) were analyzed by DTI. RESULTS: E/A > E(m)/A(m) > 1 was observed in health control group as well as the mild-moderate AOPP; E(m)/A(m) < E/A < 1 was observed in the severe AOPP group. There was significant difference between two groups. The right ventricular E/A correlated positively with E(m)/A(m) (P < 0.001). Pulmonary arterial pressure (PAP) correlated positively with right ventricular E/Em, Tei Index (P < 0.001) and negatively with right ventricular S(m), E(m) and E(m)/A(m) (P < 0.001). CONCLUSION: The right ventricle functions, in terms of contraction and relaxation, decrease in severe AOPP patients versus health control and mild moderate groups. TDI is a useful tool to assess the right ventricle functions of AOPP patients. PMID- 21029644 TI - [Cause and treatment of intracranial hypertension after sylvian cystoperitoneal shunting]. AB - OBJECTIVE: To analyze the cause and treatment of intracranial hypertension after sylvian cystoperitoneal shunting. METHODS: Sixteen cases were retrospectively reviewed. There were 10 males and 6 females. The age range was 2-19 years old (mean: 9.94). All patients had a sylvian cystoperitoneal shunt via a common low pressure tube. RESULTS: The onset time of intracranial hypertension after cystoperitoneal shunting was 3 months to 7 years (mean: 3.20 yr). Three cases underwent the operation of adjusting intracranial location of shunt tube. The original tube was removed in 12 cases. Among them, 10 cases were operated by lateral ventricle-peritoneal shunt. The other two and two cases with a remaining tube were treated successfully with dehydration drugs. CONCLUSION: The cause of intracranial hypertension is probably due to tube blockage or less draining after the shrinking or disappearance of arachnoid cyst. Adjusting the location of intracranial tube or performing a lateral ventricle-peritoneal shunt has an excellent efficacy if a dehydration therapy is unresponsive or auto-compensation fails. PMID- 21029645 TI - [Selective radiofrequency thermocoagulation for trigeminal neuralgia]. AB - OBJECTIVE: To study the technique and experience of selective radiofrequency thermocoagulation (SRFTC) for trigeminal neuralgia (TN) and the application of neuronavigation in SRFTC for TN. METHODS: SRFTC was performed in 3269 TN patients and neuronavigation-assisted SRFTC in 36 of them. Follow-up was carried out for over 2 years in 1722 cases. RESULTS: An excellent efficacy was achieved in 2590 cases, a fair outcome in 548 cases and no response in 131 cases. The recurrence rates at one and two years were 10.5% and 25.0% respectively. The efficacy was excellent in all cases treated by neuronavigation-assisted SRFTC. The effective rate was 96%. Neither serious complication nor death occurred in this series. CONCLUSION: SRFTC for TN is both safe and effective. And the neuronavigation technique can not only increase the surgical efficacy of SRFTCP for TN but also decrease the surgical risks. PMID- 21029646 TI - [Influence of coronary artery variation on the outcome of arterial switch operation]. AB - OBJECTIVE: To investigate the influence of coronary artery variation on the outcome of arterial switch operation for transposition of great arteries. METHODS: Among 280 patients undergoing arterial switch operations at our hospital from 2001 to 2008, 73 (26.1%) had concurrent coronary arteries variation (54 males and 19 females; median age: 0.6 +/- 1.1 years old; mean body weight: 5.8 +/ 2.6 kg). Of these 73 patients (variant group), 21 cases had transposition of great arteries with a ventricular septal defect and 30 cases with an intact ventricular septum. The other 22 cases were of Taussig-Bing anomalies. Another 207 cases had usual coronary arteries (usual group). Coronary artery transfer was achieved by implantation of buttons to the previously anastomosed neo-aorta. RESULTS: There were 29 early death (10.4%) including 12 cases (16.4%) in variant group and 17 cases (8.21%) in usual group (P < 0.05). Mean cardiopulmonary bypass and cross-clamp durations were 229 +/- 84 and 146 +/- 48 min in variant group while 206 +/- 59 and 137 +/- 40 min in usual group (P < 0.05). Six cases were confirmed intra-operatively as coronary compression or obstruction. Complications included infection (n = 11), low output syndrome (n = 7), diaphragm paralysis (n = 3), pericardial effusion (n = 2) and atrioventricular block (n = 2). CONCLUSION: Coronary artery variation increases the operative difficulty and influences the outcome. The operative proficiency may decrease the mortality. PMID- 21029647 TI - [The choice of thoracoscopic sympathectomy in the treatment of palmar hyperhidrosis among different procedures]. AB - OBJECTIVE: Retrospective analyze the long-term efficacy and compensatory sweating of thoracoscopic sympathectomy in the treatment of palmar hyperhidrosis by different operative methods in order to search after a better operative method. METHODS: Retrospective study of 643 cases (498 cases available) palmar hyperhidrosis who accepted video-assisted thoracoscopic bilateral sympathectomy during from 1995 to Aug 2008. The patients were divided into four groups by different operative methods. (1) Group A(n = 82): Thoracoscopic T2-4 sympathectomy was performed. (2) Group B (n = 135): Thoracoscopic T2 sympathectomy was performed. (3) Group C (n = 41): Thoracoscopic T2 sympathetic nerve clipped. (4) Group D (n = 240): Thoracoscopic T3-4 level sympathectomy plus bypass fiber (Kuntz fiber) resection on same level was performed. RESULTS: All procedures were successfully performed under thoracoscope without severe morbidity and mortality. The curative rate of palmar hyperhidrosis was 100.00%. The incidence of compensatory sweating were 54.9% (group A), 48.1% (group B), 48.8% (group C) and 28.8% (group D) respectively with significantly decrease in group D contrast to other three groups. The incidence of high-grade compensatory sweating which have important influences on daily life were 9.8% (group A), 10.4% (group B), 9.8% (group C) and 2.9% (group D) respectively with significantly decrease in group D. Other pairings have nonsignificance. The relapse rate were 1.2% (group A), 2.2% (group B), 7.3% (group C) and 0.8% (group D). Only when group D contrasted to group C has significantly decrease in the relapse rate (chi(2) = 8.423, P = 0.004). Other pairings have nonsignificance. CONCLUSION: The procedure of T3-4 sympathectomy plus bypass fiber resection is reasonable operative method to cure hyperhidrosis with the better curative effect and lowest incidence of compensatory hyperhidrosis. PMID- 21029648 TI - [Concurrent chemoradiotherapy for stage III non-small cell lung cancer]. AB - OBJECTIVE: To evaluate the immediate efficacy and acute toxicity of cisplatin based induction chemotherapy followed by weekly concomitant chemoradiotherapy and concomitant chemoradiotherapy followed by consolidation chemotherapy in unresectable stage III NSCLC. METHODS: A total of 118 patients were pathologically diagnosed as stage III N SCLC. Among them, 77 patients (A group) received two cycles of cisplatin-based induction chemotherapy, followed by 6 weekly cycles of paclitaxel 45 mg/m(2) (n = 45) and gemcitabine 350 mg/m(2) (n = 32) in combination with thoracic radiotherapy; 41 patients (B group) received concomitant chemoradiotherapy (cisplatin 50 mg/m(2), d1, 8, 29, 36/etoposide 50 mg/m(2), d1-5, 29-33, n = 18, paclitaxel 45 mg/m(2)/weekly * 6/carboplatin AUC = 2/weekly * 6, n = 23) followed by consolidation chemotherapy. All thoracic radiotherapy dose are 2 Gy per fraction and day to a total dose of 58-60 Gy. RESULTS: The total response rate of A and B groups was 80.5% and 75.6% respectively (P = 0.534). According to subgroup analyses, no statistically significant differences existed according to chemotherapy (P = 0.557). The main side-effects were neutropenia, radiation esophagitis, radiation pneumonitis and nausea/vomiting. The gemcitabine group was statistically significant different in neutropenia. CONCLUSION: Different chemotherapeutic agents in combination with thoracic radiotherapy are clinically feasible with a moderate toxicity. Their profiles of efficacy and toxicity are comparable to each other. PMID- 21029649 TI - [A clinical analysis of 137 cases of influenza A(H1N1)]. AB - OBJECTIVE: To analyze the epidemiology and clinical characteristics of influenza A (H1N1). METHODS: A retrospective analysis was performed on the clinical data of 137 cases of influenza A (H1N1) admitted into our hospital during May to August 2009. RESULTS: In the early stage, most cases were imported from the US, Australia, Canada and the UK. While in the later stage, most of them were secondary. The patients were mainly children and youngsters. And the most common clinical manifestations were fever (n = 108), cough (n = 93) and sore throat (n = 67) while the most common signs congestive throat (n = 99) and swelling tonsil (n = 46). The average fever period was 3.3 +/- 1.5 days. The clinical symptoms vanished in 4.4 +/- 1.9 days. And the average length of stay was 5.5 +/- 2.1 days. Laboratory tests: the count of leukocytes declined while that of lymphocytes increased in 39 cases (39.5%). The test of influenza A (H1N1) nucleic acid was positive. The chest radiograph showed intensive pulmonary markings or patchy pneumonia-like signs. TREATMENTS: the groups of patients using Chinese herbs, western medicine plus Chinese herbs, symptomatic relief and placebo showed no significant difference in fever period, recovery time and the negative converting period of influenza A (H1N1) nucleic acid tests became negative. CONCLUSION: Influenza A (H1N1) may be recessive or dominant. Despite a strong infectivity, the clinical symptoms are mild and the clinical course is self limited, similar to the seasonal influenza. PMID- 21029650 TI - [Relationship of oxidative DNA damage and expression of mitochondrial apoptotic proteins in rat striatum induced by 6-hydroxydopamine]. AB - OBJECTIVE: To study the relationship between oxidative DNA damage and mitochondrial apoptosis relative proteins in rat striatum induced by 6 hydroxydopamine (6-OHDA) during the pathogenesis of Parkinson's disease (PD). METHODS: 6-OHDA was stereotactically injected into the bilateral right striatum of rats to produce PD models. Assays for 8-oxo-dG immunohistochemistry and Western blot for MTH1, Cytochrome c, Cl-caspase 9 and Cl-caspase 3 in right striatum was separately conducted. RESULTS: In 10 successful PD rats, compared with either sham or normal group, there were obvious more 8-oxo-dG positive cells in lesioned striatum while there was a lower expression of MTH1. Furthermore, the expressions of such intrinsic apoptotic pathway factors as cytoplasmic Cytochrome c, Cl-caspase 9 and Cl-caspase 3 were highly up-regulated in lesioned striatum. CONCLUSION: Oxidative DNA damage plays a key role in the pathogenesis of PD. Furthermore Cytochrome c, caspase 9 and caspase 3 are involved in the regulation of apoptosis under oxidative DNA damage induced by 6-OHDA. PMID- 21029651 TI - [The study about expression of Gli2 in vein grafts]. AB - OBJECTIVE: To study the expression of cell cycle related factor Gli2 in autogenous vein graft and its relation with neointima formation. METHOD: Autogenous vein graft model were established in 36 male wistar rats of 8 weeks old, 140 g, by transplanting the left jugular vein to intra renal abdominal aorta with microsurgical technique. Graft veins were harvest at 14, 28 days after transplantation. The IF and W-B were used to detect the protein expression in the vein graft. At the same time Gli2- mRNA was measured by RT-PCR. RESULTS: Immunofluorescent staining showed that the Gli2+ cells was only 3.2% +/- 0.4% in the normal vein, but was much more in the vein graft after surgery, was 41.3% +/- 0.6%, 58.3 +/- 0.6% respectively; The expression of Gli2 and PCNA were both elevated in the vein graft. There is a positive correlation between them which indicated by W-B, the relation index was 0.826; the Gli2 mRNA content was also increased in vein graft, was 8.9, 13.6 fold compared with normal vein as 1 respectively. CONCLUSION: Gli2 is upregulated in autogenous vein grafts and may correlated with the proliferation of vascular smooth muscle cells. PMID- 21029652 TI - [Development and clinical application of elastic trephine through pedicle of fractured vertebra]. AB - OBJECTIVE: To evaluate the feasibility and surgical procedure of bone grafting with elastic trephine. METHODS: A total of 42 cases of thoracolumbar fracture received pedicle screw fixations by combining bone grafting with elastic trephine through pedicle of fractured vertebra. The ratios of the altitude of traumatic vertebra to normal altitude, kyphosis Cobb angle and sagittal index were measured by preoperative and postoperative X-ray images. RESULTS: A follow-up visit of 12 26 months (average: 14.8) showed that the dislocations of vertebrae were corrected and fusions completed. Proportion of the height of anterior edge of traumatic vertebra to normal height was (53.89 +/- 6.57)% at pre-operation, (92.31 +/- 11.25)% at post-operation and (91.39 +/- 10.28)% at an one-year follow up (P < 0.05). The kyphosis was (23.19 +/- 5.74) degrees Cobb angle at pre operation, (4.92 +/- 1.03) degrees at post-operation and (5.13 +/- 1.41) degrees at an one-year follow-up (P < 0.05). In contrast with 86% (78%-97%) on average at post-operation, the pre-operative sagittal index was 54% (32%-66%) on average. CONCLUSION: Application of bone grafting with elastic trephine can reconstruct the altitude of injured vertebral body, increase the compressive stability of anterior column as well as effectively correct the kyphosis deformity. With a convenient application, elastic trephine plays a variety of roles in both auxiliary reduction and bone grafting reconstruction. PMID- 21029653 TI - [Critical issues in the clinical application of advanced computed tomography]. PMID- 21029655 TI - [Study of variations in adult sphenoid sinus by multislice spiral computed tomography]. AB - OBJECTIVE: Explore the anatomic variations of adult sphenoid sinus and delineate the precise relationship between sphenoid sinus and adjacent structures. METHODS: Using multi planner reformation (MPR), the images of 260 spiral computed tomography (CT) scans were reviewed through a doctor station. RESULTS: The sphenoid was divided into 6 types: no development, conchal, pre-sellar, half sellar, full-sellar and post-sellar. The prevalence was 0.19%, 1.54%, 8.08%, 22.88%, 20.58% and 46.73% respectively. And there was no difference between left and right. The prevalence of accessory septa or bone spur inside sphenoid sinus was 51.5%. With the gasification spreading, the prevalence was rising. And there was statistical significance among them. The dorsum sella was divided into three types: I, II, III. And its prevalence was 48.08%, 25.19% and 26.73% respectively. The difference of sphenoethmoid distribution among the various type sinus had no statistical significance. The prevalence of vidian canal and foramen rotundum protrusion was 39.2% and 15.8% respectively. And all occurred in pterygoid process cells. Internal carotid artery (ICA) was divided into 4 types. And the prevalence of type 0 to 3 was 13.5%, 50.0%, 26.9% and 9.6% respectively. With the gasification spreading, the prevalence of types 2, 3 was rising. And there were statistical significance among them. The prevalence of type 0 to 4 CNII was 4.4%, 19.2%, 26.0%, 29.0% and 21.4% respectively. With the gasification spreading, the prevalence of type 3, 4 CNII was rising. And the difference had statistical significance. CONCLUSION: MPR and multislice spiral CT can facilitate a precise study of anatomic variations in adult sphenoid sinus and delineate the relationships between sphenoid sinus and adjacent structures. Caution must be exercised during sphenoid and trans-sphenoid surgery to minimize the risk of inadvertently injuring the adjacent structures. PMID- 21029654 TI - [Diagnostic value of 64 multislice CT in typing of congenital aortic anomaly in neonates and infants]. AB - OBJECTIVE: To study diagnostic value of 64 multislice CT in typing of congenital aortic anomaly in neonates and infants. METHODS: 120 pediatric patients (under one year of age) with congenital heart disease (CHD) underwent 64 contrast enhanced MSCT before a corrective operations. The diagnostic sensitivity, specificity and accuracy of 64 MSCT were evaluated and also compared with those of echocardiography with Doppler. The patients were randomly assigned to two groups (72 and 48 persons) respectively according to tube tension of 80 and 100 kV. The differences of the image qualities were compared between them. RESULTS: 36 congenital aortic anomalies were found (36/120, 30%) by 64 MSCT, which were furtherly distinguished into 2 cases in double aortic arch, 2 cases in left-sided aortic arch with aberrant right subclavian artery, 22 cases in right aortic arch (6 cases in right-sided aortic arch with aberrant left subclavian artery, 12 cases in right aortic arch with mirror image branching), 10 cases in coarctation of aorta. Diagnostic sensitivity, specificity and accuracy of 64 MSCT were all 100%. By contrast, those of echocardiography with Doppler were 27.8%, 97.6%, 76.7%, respectively. The quality scores were 4.69 +/- 0.52, 4.58 +/- 0.58 at 80 kV and 100 kV, respectively. No significant statistical difference was found between them (t = 1.08, P = 0.28). CONCLUSION: MSCT allows a detailed assessment of the anatomy of congenital aortic anomaly, which can be used as an important supplementary method in diagnosing CHD and offer important information for operation. 80 kV should be selected in CHD patients less than one year old for CT examination to reduce radiation exposure. PMID- 21029656 TI - [Differentiation of subtypes of renal cell carcinoma by double-phase helical computed tomography]. AB - OBJECTIVE: To evaluate the imaging features of different subtypes of renal cell carcinoma (RCC) by double-phase helical computed tomography (CT) and to enhance its pre-operative diagnosis level. METHODS: A total of 460 RCC were reviewed retrospectively. Tumor size, enhancement degree, enhancement drop between corticomedullary (CMP), nephrographic (NP), enhancement pattern, and tumor density (homogeneity, degeneration or necrosis, calcification) were observed respectively. The clear cell, chromophobe and papillary types were analyzed for statistical analysis. RESULTS: They had difference in enhancement pattern and tumor density of clear cell, chromophobe (P < 0.05) and papillary types (P < 0.05). There were differences in enhancement degree, enhancement drop and combine degeneration or necrosis in all subtypes of RCC (P < 0.05). The clear cell type was of hypervascular tumor and showed a stronger enhancement (80.9%) than other types. The enhancement drop was also higher than other types and 57.9% of it was >= 30 HU. As for >= 30 HU, the clear cell type was diagnosed with a 57.9% sensitivity and a 91.9% specificity. Clear cell type tended to appear as peripheral and heterogeneous enhancement (66.3%, 94.6%); it was likely heterogeneous in density (91.6%) with frequent degeneration or necrosis (60.5%). The chromophobe type was of moderate vascular tumor and it exhibited middle-level enhancement (77.1%). The enhancement drop was low (< 30 HU, 80.0%). As for 0-30 HU, the chromophobe type was diagnosed with an 80.0% sensitivity and a 66.1% specificity. Its pattern ended to appear as homogeneous enhancement (65.7%); Homogeneous density, degeneration and necrosis were characteristic signs of chromophobe type. The papillary type was of hypovascular tumor and it exhibited slight or no enhancement (70.4%). The enhancement drop was low (< 30 HU, 92.6%) and the gradual enhancement (63.0%) was characteristic of this type. As for 0 Hu, the papillary type was diagnosed with a 63.0% sensitivity and a 91.8% specificity. It tended to appear as homogeneous density (63.0%). The unclassified type tended to appear as peripheral (9/12 cases) and stronger enhancement (7/12 cases) and heterogeneous density with degeneration or necrosis (9/12 cases). The multilocular cystic RCC appeared as complex cyst. And cystic wall enhancement was an important diagnostic point of cystic RCC. CONCLUSION: Double-phase helical CT plays an important role in the pre-operative differentiation of subtypes of RCC. Each type of RCC has its own features. A clinician may reach a correct pre operative diagnosis. PMID- 21029657 TI - [Clinical therapeutic effect and biological monitoring of p53 gene in advanced hepatocellular carcinoma]. AB - OBJECTIVE: To investigate the therapeutic effect and biological changes of hepatic arterial perfusion of p53 gene via port catheter system (PCS) on advanced hepatocellular carcinoma. METHODS: A total of 48 cases of advanced hepatocellular carcinoma were divided into the experimental group (30) and the control group (18). Transiliac external artery PCS implantation was performed in all cases. p53 gene was perfused into target artery confirmed by angiography. In the experimental group, 10(12) VP of p53 gene and 20 mg OPT were employed every week as a course for 21 days. In the control group, only 20 mg OPT was used. KPS, AFP and the survival period, RECIST (response evaluation criteria in solid) tumor were analyzed. Flow cytometry (FCM) and micronucleus (MN) assay in vivo were used to detect p53 gene mutation and spontaneous micronucleus formation in peripheral blood of the experimental group. RESULTS: The experimental group were performed 1 to 8 courses. There was a significant difference with AFP level and KPS in the experimental group(P < 0.05). However there was no significant difference (P > 0.05) in the control group. After one month, survival rate of the the experimental group and the control group was 96.6% and 94.4%, there was a significant difference between the two groups in objective tumor relieve (P < 0.05). After three months, survival rate of the the experimental group and the control group was 83.3% and 55.6%, there was a significant difference between the two groups in objective tumor relieve (P < 0.05). After six months, survival rate of the the experimental group and the control group was 50.0% and 11.1%, there was a significant difference between the two groups in objective tumor relieve (P < 0.05). After nine months, survival rate of the the experimental group and the control group was 23.3% and 0%, there was a significant difference between the two groups in objective tumor relieve (P < 0.05). After twelve months, survival rate of the the experimental group and the control group was 6.67% and 0%, there was a significant difference between the two groups in objective tumor relieve (P < 0.05). The depression of p53 expression was observed in the HCC patients who were employed four times of intervention operations. The difference of p53 expression between before and after interventional rAd-p53 therapy were statistically significant (P < 0.01). The frequency of MN depressed by the rAd p53 was seen in the patients, and the differences of the frequency of MN between before and after interventional rAd-p53 therapy were statistically significant (P < 0.05). CONCLUSION: p53 gene sequential infusion via hepatic artery is effective for advanced hepatocellular carcinoma. The biological study will play a important role in selecting the therapeutic dose and judging therapeutic efficacy by means of guiding and monitoring. PMID- 21029658 TI - [Clinical analysis of the treatment:transcatheter arterial chemoembolization combined with sorafenib in advanced hepatocellular carcinoma]. AB - OBJECTIVE: To provide more evidence sources to the standard treatment for patients with advanced hepatocellular carcinoma, the writer analyze patients' time to progression (TTP) and overall survival (OS) after patients receiving transcatheter arterial chemoembolization (TACE) combined with sorafenib as a treatment of advanced hepatocellular carcinoma (HCC); observe the healing effect embolization combined with anti-angiogenic treatment for advanced hepatocellular carcinoma; and also analyze treatment of security. METHODS: There are 36 patients, 33 male and 3 female had been Pathologically or clinical diagnosis. After receiving Transcatheter Arterial Chemoembolization (TACE) therapy, in the following 3 to 7 days, this group of patients continuously take sorafenib (brand name: Nexavar) (per tablet 200 mg), 2 tablets each time, 2 times a day. Every 4 to 8 weeks is called as one period of treatment. Referring to RECIST Evaluation, the writers mainly observe patients' tumor progression (TTP) and overall survival (OS), record adverse events. Using life table method to analyze survival rate, using Kaplan-Meier method to analyze all the survival curves. RESULTS: Till March, 2010, 14 of 36 evaluable patients died and 22 survive; the median time to tumor progression (mTTP) to 8.62 months (95%CI: 6.51-10.24 months); the median survival time (mOS) of 12.41 months (95%CI: 9.57-14.80 months). The overall survival rate to observation period is 61.1%; 36 patients had been studied, 22 survive. Among the survivals, there is no CR cases, and 1 case PR, 15 patients SD, 6 patients PD; disease control rate (DCR) (CR + PR + SD) is 44.4%. The side effects of taking Sorafenib mainly are hand-foot skin reaction, diarrhea, fatigue and loss of appetite. These side effects can be markedly eased after symptomatic treatment. CONCLUSION: Combined with sorafenib treatment may give patients with advanced hepatocellular carcinoma a longer longevity and keep the disease in a steady state. This therapy can be added into the treatments to patients with advanced hepatocellular carcinoma. The side effects of taking Sorafenib (Nexavar) could be stand. PMID- 21029659 TI - [Polymorphism of HLA-DRB1 and -DQB1 alleles among young women with cervical squamous cell carcinoma and its relation with human papillomavirus type 16 infection]. AB - OBJECTIVE: To investigate the polymorphism of human leukocyte antigen (HLA)-DRB1 and -DQB1 alleles among young women with cervical squamous cell carcinoma (SCC) and elucidate its relationship with human papillomavirus (HPV) type 16 infection. METHODS: From January 2005 to August 2009, 166 women diagnosed with cervical SCC at our hospital were enrolled. These patients were divided into two groups based on age, including 59 cases in young age group (<= 35 yrs) and 107 cases in non young age group. In the mean time, 50 cases with uterine myoma treated by hysterectomy were selected as controls. HPV 16 DNA in cervical tissues was amplified by polymerase chain reaction (PCR). HLA-DRB1 and -DQB1 typing were carried out by PCR-sequence specific primer (PCR-SSP) and the allele frequencies calculated. RESULTS: (1) The allele frequency of HLA DQB1*0301 at 29.6% was detected among HPV 16 positive cervical SCC cases in young age group. And it was significantly higher than 12.9% of non-young age group (P < 0.05). The allele frequencies of HLA-DRB1*04 and -DRB1*09 were significantly higher among HPV 16 negative cervical SCC cases in young age group as compared with non-young age group (14.1%, 26.6% vs 5.9%, 10.5%) (P < 0.05). The HLA-DRB1*07 allele was not detected among HPV 16 negative cervical SCC cases in young age group, But 14 cases (9.2%) were detected in non-young age group (P < 0.05). (2) The allele frequencies of HLA-DQB1*0501 at 7.4% and 6.3% respectively were detected among HPV 16 positive and negative cervical SCC cases in the young age group. And they were significantly lower than 25.8% and 20.4% of non-young age group (P < 0.05). CONCLUSION: The distribution patterns of HLA-DRB1 and -DQB1 alleles among young women with cervical SCC are different from those of older ones. And it has something to do with the HPV 16 infection status. PMID- 21029660 TI - [Using MR PC cine to evaluate CSF dynamics in neuroendoscopic third ventriculostomy:an analysis of 146 cases]. AB - OBJECTIVE: To evaluate the change of CSF dynamics using MR PC Cine for neuroendoscopic third ventriculostomy. METHODS: 146 cases of hydrocephalus were treated by neuroendoscopic third ventriculostomy including 36 cases checked with MR PC Cine study randomly. The successful result was assessed by clinical symptom and imaging study. All the patients were given 3 months to 1 year follow-up. RESULTS: The symptoms of 121 (83%) patients were recovered soon. CT, MRI and MR PC Cine demonstrated the CSF velocity, flow rate and dynamics change to the normal level compared with preoperative check. The effective rate of this group was 75.3% with one year follow-up. CONCLUSION: The method of MR PC Cine to evaluate the CSF dynamics result for neuroendoscopic third ventriculostomy is simple, fast and safe. It is worth the clinical application. PMID- 21029661 TI - [Analysis of non-surgical candidates after presurgical evaluation for epilepsy surgery]. AB - OBJECTIVE: To investigate the causes of non-surgical candidates after presurgical evaluation for epilepsy surgery. METHODS: A retrospective review was conducted for the clinical data of 112 non-surgical candidates after presurgical evaluation for epilepsy surgery. Potential surgical candidates were identified through a detailed seizure and medical history, physical examination, and uses of video electroencephalography and neuroimaging. RESULTS: The common causes of non surgical candidates after presurgical evaluation for epilepsy surgery were patients and their families giving up intracranial electrode positioning for various reasons (42/112, 37.5%), multifocal epileptogenic zones (29/112, 25.9%), generalized seizures (15/112, 13.4%), pseudoseizure or slight seizure (10/112, 8.9%; 7/112, 6.3%), epileptogenic zone in functional areas (6/112, 5.4%) and so on. CONCLUSION: Epilepsy surgery is less likely in patients with a history of severe encephalitis and perinatal brain injury and diffuse, multiple, bilateral abnormality on cranial MRI. Unnecessary presurgical evaluation can be avoided by distinguishing generalized seizures, pseudoseizure and progressive brain disease. Patients and their families still have doubts about the surgical risks, costs and effects. It is important to inform the patients of the potential risks and benefit of surgery. PMID- 21029662 TI - [Effect of recombinant human tumor necrosis factor receptor type II-Fc fusion protein antibody on cytokines and bone metabolism in patients with juvenile idiopathic arthritis]. AB - OBJECTIVE: To evaluate the influence of the recombinant human type II tumor necrosis factor receptor-antibody Fc fusion protein (rhTNFR:Fc) on cytokines and bone metabolism in patients with juvenile idiopathic arthritis (JIA). METHODS: This was a prospective, non-randomized, controlled and open-label study. Thirty one patients with JIA in active state were enrolled at our hospital from December 2006 to June 2009. The mean age was 12.7 +/- 2.3 years. Exclusive criteria included infection with tuberculosis and hepatitis B etc., abnormal renal or hepatic function. Study consists of two phases. During the first phase (0-3 months), according to the economic status, all JIA patients were divided into treatment and control groups. The treatment group consisted of 18 patients (enthesitis-related arthritis, n = 15; polyarticular-onset arthritis, n = 2; systemic-onset type, n = 1) on a regimen of rhTNFR:Fc 0.4 mg/kg, subcutaneously injected twice weekly. The control group contained 13 patients (enthesitis related arthritis, n = 9; polyarticular-onset arthritis, n = 2; systemic-onset type, n = 2) on a regimen of MTX 10 mg * m(-2) * w(-1). Two intolerance patients were given sulfasalazine (SASP) 30-50 mg * kg(-1) * d(-1). During the second phase (3-6 months), the responding patients continued the original therapy. The rhTNFR:Fc group received a reduced dosage of 0.4 mg * kg(-1) * w(-1). All patients of both groups who became complicated with peripheral arthritis or were non-responding had the addition of SASP. Follow-up was conducted at baseline, 1 month, 3 months and 6 months. And TNF-alpha, MMP-3, IL-1beta, osteocalcin (BGP), beta-collagen fragment (beta-CTx), alkaline phosphatase, erythrocyte sedimentation rate (ESR), c-reactive protein (CRP) and bone mineral density dynamic changes were examined respectively in the treatment process. RESULTS: Alkaline phosphatase and lumbar spine bone mineral density increased while TNF alpha, IL-1beta, ESR and CRP decreased significantly in two groups (P < 0.05). ESR were 16 +/- 8.0 mm/h vs 60 +/- 38 mm/h, CRP 10 +/- 7 mg/L vs 47 +/- 37 mg/L and beta-CTx 2.1 +/- 0.8 vs 1.1 +/- 0.9 ug/L at 1 month in two groups respectively with statistic difference (P < 0.05). BGP increased and MMP-3 decreased in both groups with no statistic difference. Femur Ward's triangular area and forearm bone mineral density had no statistic difference between two groups. Interestingly, one case with bone fracture for two years has healed after a 6-month therapy of rhTNFR:Fc as proved by X-ray. CONCLUSION: Both rhTNFR:Fc and traditional DMARDs both can reduce the levels of TNF-alpha, IL-1beta, ESR and CRP and increase lumbar spine bone mineral density and ALP significantly. RhTNFR: Fc improves the acute phase index and bone metabolism index earlier than the traditional therapy. Thus disease and bone destruction are controlled more earlier. PMID- 21029663 TI - [Ropivacaine volume for ultrasound-guided retrograde infraclavicular brachial plexus block]. AB - OBJECTIVE: The aim of this study was to determine the medium effective volume required to produce an effective retrograde infraclavicular block using an ultrasound (US)-guided technique. METHODS: Thirty adults undergoing elective upper limb surgery received a US-guided retrograde infraclavicular block. The initial concentration of 0.5% ropivacaine injected was 30 ml, which was subsequently varied at a ratio of 1:1.2 for each consecutive patient according to the response of the previous patient. The medium effective volume (EV50) was determined using the Dixon and Massey up-and-down method. The effective volume in 95% of patients (EV95) was calculated using probit regression. RESULTS: The medium effective volume and calculated effective volume in 50% and 95% of patients were 23.6 ml (95% confidence interval, 21.3-26.2 ml) and 32.3 ml, respectively. No patient required a general anesthesia. CONCLUSION: The appropriate volume of 0.5% ropivacaine required for US-guided retrograde infraclavicular block was 30 ml in clinical practice. PMID- 21029664 TI - [A comparative study of survival time of surgery combined with chemotherapy and non-surgical chemotherapy in SCLC]. AB - OBJECTIVE: To compare the survival time of surgery combine with chemotherapy with non-surgery chemotherapy in SCLC. METHODS: 37 SCLC post operation patients were received 4-6 cycles of chemotherapy of "etoposide + cisplatin or carboplatin". 37 SCLC patients were selected be control group, whose age, stage and site of tumor were similar to surgery combine with chemotherapy group, and received 6 cycles of chemotherapy of "etoposide + cisplatin or carboplatin". Two groups were followed up 5 year and compared with the survival time. RESULTS: The 1, 3, 5 year survival rate of surgery combined with chemotherapy group were 72.97%, 35.13%, 21.62%. The 1, 3, 5 year survival rate of control group were 54.05%, 13.51%, 5.41%. The survival rate of stage I (P = 0.01) was significantly different, but stage II (P = 0.06) and stage III (P = 0.836) were no difference between the two group of SCLC. CONCLUSION: It was found that surgery combined with chemotherapy got satisfactory effects in stage I SCLC. PMID- 21029665 TI - [Effects of rotating cell culture system on constructing of tissue engineering intervertebral nucleus pulposus]. AB - OBJECTIVE: To study the effect of rotating cell culture system (RCCS) on the in vitro constructing of tissue engineering nucleus pulposus. METHODS: Nucleus pulposus cells from rabbit thoracic and lumbar intervertebral discs were proliferated in vitro to the third generation and seeded into PLGA (poly-lactide co-glycolide) scaffolds (3 * 10(7)/ml). Experimental group was subjected to the RCCS while the control group was cultured under a normal condition. Both groups were cultured in vitro. The complex of nucleus pulposus and scaffolds was observed after 4 weeks. Tissue texture, scanning electron microscope, type II collagen, content of GAG (glycosaminoglycan) and DNA were assessed. RESULTS: After 4 weeks, the tissue engineered nucleus pulposus under RCCS were morphologically thicker and bigger. And the content of GAG, DNA and percentage of typeII collagen were more than those in the control group. The structural arrange of tissue engineering nucleus pulposus was visualized directly. CONCLUSION: The RCCS promotes intervertebral disc cells to secrete collagen and GAG. It may benefit the construction of tissue engineering intervertebral disc. PMID- 21029666 TI - [Clinical value of NT-proBNP in the diagnosis and analysis of correlation of NT proBNP with clinical and echocardiographic findings in patients with aortic stenosis]. AB - OBJECTIVE: To evaluate the diagnostic value of NT-proBNP in patients with aortic stenosis (AS), analyze the relation of NT-proBNP to NYHA functional class and echocardiographic findings. METHODS: Measured the whole venous blood of NT-proBNP with enzyme linked immuno sorbent assay in 40 aortic stenosis patients (AS group) and 76 normal subjects (control group). We assessed the diagnostic value of NT proBNP for aortic stenosis, and related NT-proBNP to clinical NYHA functional class and echocardiographic findings. RESULTS: Compared to controls, NT-proBNP levels had significantly higher in patients with aortic stenosis (P < 0.01). The level of NT-proBNP was gradually and significantly increased with the NYHA functional II, III and IV class compared to controls (all P < 0.01). NT-proBNP was significantly (3.5 times) higher in mild/moderate stenosis group than that in control group (2.95 +/- 0.48 vs 2.63 +/- 0.10, P < 0.05), and was significantly (6.0 times) higher in severe stenosis group than that in control group (3.16 +/- 0.50 vs 2.63 +/- 0.10, P < 0.01). LVMI was significantly (1.7 times) higher in mild/moderate stenosis group than that in control group (169 +/- 51 vs 100 +/- 22, P < 0.01), and was significantly (2.1 times) higher in severe stenosis group than that in control group (212 +/- 86 vs 100 +/- 22, P < 0.01). The NT-proBNP values of 1150 ng/L and 1356 ng/L were determined as the best cutoff values for the diagnosis of patients with mild/moderate (AUC = 0.657, P < 0.05) and severe aortic stenosis (AUC = 0.848, P < 0.01), the sensitivity, specificity and accuracy were 61.11% and 77.30%, 69.74% and 96.10%, 68.09% and 91.80%. Log (NT proBNP) was significantly positively related with LVEDD, LVMI and mean transvalvular pressure gradient (MTPG) (all P < 0.05), and negatively related with LVEF (P = 0.01) in univariate analysis. In multiple regression analyses, NYHA functional class, LVEF and Log (MTPG) was independently associated with NT proBNP. CONCLUSION: NT-proBNP is valuable for the diagnosis of patients with aortic stenosis. NT-proBNP has correlation with the heart function and severity of the aortic stenosis. PMID- 21029667 TI - [Recombination of HLA haplotypes in Guangdong Han nationality]. AB - OBJECTIVE: To analyze the human leukocyte antigen complex class I (-A, -B & -C) and class II (-DRB1 & -DQB1) linked haplotypes of Guangdong Han nationality and to study the recombination events of five classical loci in the inheritance of HLA haplotypes. METHODS: A total of 939 peripheral blood samples were collected from 198 families in Guangdong Han nationality who came to our center for HLA typing from 2000 August to 2009 December. HLA-(A, B & DRB1) and HLA-(C & DQB1) alleles were typed by low-resolution polymerase chain reaction-sequence specific oligonucleotide probes (PCR-SSO) and PCR-sequence specific primers (PCR-SSP) methods respectively. Then the recombination sites were analyzed by familial study. The samples of 52 individuals from the families with exchange recombination were analyzed by the sequence-based typing (SBT) to judge whether the recombination was interallelic or interlocus exchange. RESULTS: Among 543 offspring individuals of 198 families in Guangdong Han nationality, 9 individuals with HLA-A-C-B-DRB1-DQB1 linked haplotypes had a recombination rate of 1.657%. Among 9 HLA haplotypes recombined families, 3 of them were found to have a crossover between HLA-A and -Cw loci and 6 of them a crossover between HLA-B and DRB1 loci. Four of these recombination events occurred in the most common haplotypes A*3303-Cw*0302-B*5801-DRB1*0301-DQB1*0201 of Guangdong Han nationality. Among 9 cases of recombination, 5 of them were formed by a crossover between maternal chromosomes and 4 cases a crossover between paternal chromosomes. Three individuals with an exchange between A/Cw loci were all females. Among 6 cases with an exchange between B/DRB1 loci, 5 of them were males and 1 case was female. CONCLUSION: During the inheritance, recombination of HLA linked haplotype mainly occurred between A/Cw loci and B/DRB1 loci, the recombination is related to the haplotype-specificity and sex-specificity. PMID- 21029668 TI - [Influence of HLA-A, B loci carrying Bw4 motif on HIV CD4 T cell count and viral load]. AB - OBJECTIVE: To analyze the influence of Bw4 motif carried by HLA-A, B loci on CD4 T cell count and viral load of primary HIV infectors. METHODS: The technique of SSP-PCR was employed to detect the HLA-A, B allele typing in 95 HIV infectors. And the roles of Bw4 motif carried by HLA-A, B loci on CD4 T cell count and viral load were analyzed. RESULTS: (1) The population frequency of HLA-A, B loci carrying Bw4 motif was respectively 32.6% (31/95) and 60.0% (57/95). The population frequency of Bw4/4, Bw4/6, Bw6/6 located on HLA-B was 21.1% (20/95), 38.9% (37/95) and 40.0% (38/95) respectively. (2) Compared with those with CD4 T cell count less than 500/ul, more Bw4 motifs were expressed on HLA-A, B loci of patients with CD4 cell count more than 500/ul (mean rank, 56.7 vs 41.6, U = 749.5, P < 0.01). Moreover, the fewest infectors were those with HLA-A, B carrying 3 Bw4 motifs and CD4 T cell count fewer than 500/ul (1 case). And secondly were those with HLA-A, B carrying 0 or 3 Bw4 motif and CD4 cell count more than 500/ul (7 cases, chi(2) = 12.6, P < 0.01). (3) The infectors with HLA A, B loci carrying 3 Bw4 motifs had more CD4 T cell count (median: 651/ul) and less viral load(lg median: 3.43)than those with HLA-A, B carrying 0 or 1 Bw4 motif (430 and 425/ul, 4.48 and 4.40). And the difference was significant (all P < 0.05). However, the CD4 cell count and viral load between the patients with HLA A, B carrying 2 Bw4 motifs and 3 Bw4 motifs were insignificantly different (P > 0.05). (4) Irrespective of Bw4 motif on HLA-A locus, the infectors HLA-B carrying Bw4/4 homozygote had more CD4 cell count (median: 538/ul) and less viral load (lg median: 3.53) than those carrying Bw4/6 heterozygote or Bw6/6 homozygote (433/ul and 427/ul, 4.29 and 4.48, all P < 0.05). However, irrespective of Bw4 motif on HLA-B, the CD4 cell count and viral load were insignificantly different between the infectors HLA-A carrying Bw4 motif and non-Bw4 motif. CONCLUSION: Bw4 motifs can increase the CD4 cell count and decrease the viral load of patients with primary HIV infection. Maybe Bw4/4 homozygote on HLA-B plays a role of delaying the disease progression. PMID- 21029669 TI - [Analysis on long-term compliance of anticoagulation treatment and demands of disease management in patients with atrial fibrillation]. AB - OBJECTIVE: To analyze the long-term compliance of oral anticoagulant therapy and the demands of disease management in patient with atrial fibrillation (AF). METHODS: Inpatients with AF taking warfarin were collected from Department of Internal Medicine from January 1 to December 31, 2008. Inpatients from departments of surgery, ophthalmology, otorhinolaryngology, dermatology and pediatrics and those on a previous warfarin therapy were excluded. The data of patient profiles, medical history and anticoagulant treatment were collected from electronic medical record. And the status of anticoagulant treatment one year later and demands of disease management were inquired by telephone. RESULTS: A total of 268 AF patients received a telephone survey. Among them, 145 patients (54.1%) continued taking warfarin. Gender, age, type of AF, duration of AF and history of ischemic stroke was not significantly associated with the compliance of anticoagulant treatment. The odds ratio was 1.74 (95%CI: 0.67-4.47), 0.87 (95%CI: 0.30-2.53), 1.59 (95%CI: 0.35-1.09), 1.09 (95%CI: 0.61-1.93) and 0.44 (95%CI: 0.12-1.60) respectively. Among patients on warfarin, INR was monitored monthly in 88 patients (60.7%) and 70 patients (48.3%) had an INR value of 2.0 3.0. Among 123 withdrawal patients, 88 patients (71.5%) terminated treatment within 6 month. The common reasons included patient ignorance about long-term anticoagulant treatment (35.0%) and switching to aspirin because of a poor effect (24.4%). About 80% of patients wished to obtain instructions about INR monitoring and adjustment of drug dosage. Among them, 196/268 patients (73.1%) wished for a regular follow-up. And 176/196 patients (89.8%) opted for a telephone follow-up and 150/176 patients (85.2%) wanted to receive monthly instructions. CONCLUSION: The compliance of anticoagulation treatment and the target-meeting proportion of INR value are relative low. And the common reasons of withdrawal are patient ignorance about long-term anticoagulant treatment and switching to aspirin because of a poor effect. Disease management will meet most of AF patients' demands. PMID- 21029670 TI - [Evaluative effect of TVCDS in screening and preoperative phasing endometrial carcinoma]. AB - OBJECTIVE: To examine the evaluative effect of preoperative transvaginal color Doppler sonography (TVCDS) screening and phasing of endometrial carcinoma. METHODS: A total of 713 jeopardized endometrial carcinoma patients were screened by TVCDS. The investigators observed the endometrium form, focus location, size and echo, measured the endometrium thickness, judged the regularity and integrity of edge, the integrity of faint echo halos at the interface between endometrium and muscularis and the blood flow inside focus, examined resistance index and determined endometrial carcinoma as well as muscularis infiltrating extent. According to the FIGO's phasing scheme in 1988, endometrial carcinoma was divided into I, II, III and IV phases so as to compare the results of TVCDS in screening and phasing of endometrial carcinoma with that of operative pathology. RESULTS: One hundred cases were diagnosed as endometrial carcinoma. Among which, 96 were proved by surgical pathology as endometrial carcinoma. The rates of TVCDS screening and phasing coincidence were 96% (96/100) and 94% (94/100) respectively. CONCLUSION: The application of TVCDS may diagnose and stage the cases of endometrial carcinoma. It is a valuable tool for selecting therapeutic regimens and making prognostic evaluations. PMID- 21029671 TI - [Effect of previous statins on prognosis of octogenarian patients with coronary heart disease with percutaneous coronary stenting]. AB - OBJECTIVE: To evaluate the effect of statin pretreatment on prognosis of octogenarian patients with coronary heart disease with percutaneous coronary intervention (PCI). METHODS: A total of 90 patients aged at 85 years old and over with coronary heart disease (CAD) undergoing stenting were enrolled. The duration of statin, hospitalization and one-year clinical follow-up outcome including all cause mortality, major adverse cardiac event (MACE), stroke and other major hemorrhages were collected and analyzed. RESULTS: Among these patients, 33 (36.7%) received a statin pre-treatment for at least 2 days and 57 (63.3%) did not. Patients on a statin pre-treatment were more likely to have hypertension, hyperlipidemia and a history of myocardial infraction and PCI. The procedure characteristics were similar between two groups. Despite the higher risk profile, the patients on a statin pre-treatment had a lower hospitalization MACE rate (3.0% vs 10.5%, P = 0.05). However, at one year, the patients on a statin pre treatment had a similar MACE rate (6.1% vs 3.8%, P = 0.07) as the other group. CONCLUSION: The statin pretreatment in octogenarian CAD patients with PCI may be associated with a reduced hospitalization MACE rate. PMID- 21029672 TI - [Role of papillomavirus in adenocarcinoma of esophagogastric junction]. AB - OBJECTIVE: To determine if human papillomavirus (HPV) infection could be associated with the development of adenocarcinoma of esophagogastric junction (AEG). METHODS: A total of 106 consecutive AEG patients and 59 consecutive gastric carcinoma patients who accepted surgery at our department between January 2004 and December 2006 were selected. Specimens from tumors and uninvolved mucosa were obtained intra-operatively. Genomic DNA was extracted by the phenol chloroform-isoamyl alcohol extraction protocol. The HPV infection was determined by PCR using primer set SPF1 and GP6+. Specificity of the amplified products was confirmed by sequencing. RESULTS: The HPV infection rates in AEG and gastric cancer were 10.4% (11/106) and 10.2% (6/59) separately (P = 0.966). CONCLUSION: HPV is not a major factor in the carcinogenesis of AEG type II, AEG type III or stomach. PMID- 21029673 TI - [Feasibility study of preserving intercostobrachial nerve during dissection for breast carcinoma: evidences from a preliminary pathologic exploration]. AB - OBJECTIVE: To determine the feasibility of preservation of intercostobrachial nerve (ICBN) in breast cancer. METHODS: During June 2004 to June 2006, 99 patients with operable breast cancer receiving an axillary lymph node dissection at our department were analyzed. The extirpated ICBN and ambient tissues were tested by HE staining to observe the pathological changes. RESULTS: In 96 (96.97%) cases with ICBN sacrificing, the nerves were not violated microscopically and the nerve cells remained intact. Of 28 patients with axillary lymphadenectasis, only 3 cases (10.71%) were found to have tumor emboli in the peri-neural vessels. CONCLUSION: The preservation of ICBN is a feasible and safe technique. The operative approach should be advocated. If at all possible, a surgeon should identify ICBN and preserve it. PMID- 21029674 TI - [Clinical effects of alprostadil injection on acute kidney injury after cardiac surgical procedures]. AB - OBJECTIVE: To explore the clinical effects of alprostadil injection on acute kidney injury (AKI) after cardiac surgical procedures by a prospective randomized controlled trial. METHODS: A total of 63 AKI-patients after cardiac surgical procedures were randomly divided into the control group (n = 31) and the study group (n = 32). All patients received routine therapy while patients in the study group were additionally given alprostadil injection (10 ug i.v. once every 12 hours) for 7 days. A 11-year-old patient weighing 29 kg was given half of the conventional dose. During the period of control treatment (7 days), 1 patient in the control group and 2 patients in the study group were excluded because of hemodialysis or peritoneal dialysis. Urine volume, urine beta-N acetylglucosaminidase, urine alpha(1)-microglobulin, urine beta(2)-microglobulin, serum creatinine and blood urea nitrogen were measured before and after the control treatment. And the ICU stay duration and the percentage of dialysis after the control treatment were calculated. Adverse reactions of alprostadil injection were observed simultaneously in the study group. RESULTS: After the treatment, urine volume in the study group was obviously more than that in the control group [(65.9 +/- 3.1) ml/h vs (58.8 +/- 4.5) ml/h, P < 0.05] while urine beta-N acetylglucosaminidase, urine alpha(1)-microglobulin, urine beta(2)-microglobulin, serum creatinine and blood urea nitrogen in the study group were obviously lower than those in the control group (all P < 0.05). The ICU stay duration in the study group was obviously less than that in the control group [(12 +/- 5) d vs (17 +/- 5) d, P < 0.05]. But there was no significant difference in the percentage of dialysis after the control treatment between two groups (3.3% vs 6.7%, P > 0.05). And no serious adverse reaction was reported in the study group. CONCLUSION: On the basis of routine therapy, alprostadil injection may promote the recovery of renal function in AKI-patients after cardiac surgical procedures. PMID- 21029675 TI - [Pro-apoptotic effect of ciglitazone in leukemic HL-60 cells via PPARgamma and P38 MAPK signaling pathway]. AB - OBJECTIVE: To investigate the apoptosis-inducing effect of peroxisome proliferator-activated receptor gamma (PPARgamma) agonist ciglitazone (CGZ) on leukemic HL-60 cells and its mechanisms of action. METHODS: HL-60 cells in vitro culture medium were subject to different concentrations of CGZ (10-50 umol/L) for 24, 48 and 72 h. MTT assay was used to detect the cell inhibitory rate and agarose gel electrophoresis to observe DNA fragmentation. Flow cytometry (FCM) and Annexin V/PI staining were used to detect CGZ and/or GW9662 (PPARgamma antagonist)-induced cell apoptosis. The expression of PPARgamma was examined by RT-PCR and Western blotting. The caspase-3 and protein levels in mitogen activated protein kinase signaling pathways (MAPKs, p-P38, p-ERK and p-JNK) were also detected. RESULTS: CGZ (over 30 umol/L) could inhibit the growth of HL-60 cells in both time- and dose-dependent manner. After treatment for 72 h, the cell growth inhibitory rate in 50 umol/L CGZ (84% +/- 11%) treated cells was found more higher than that in both 40 umol/L and 30 umol/L CGZ treated cells (72% +/- 13%, 59% +/- 13%, P < 0.01) and a typical DNA ladder was also observed by agarose gel electrophoresis. The expression of PPARgamma was gradually up-regulated by CGZ treatment and could be down-regulated partially by PPARgamma antagonist GW9662. The results also revealed that CGZ-induced cell apoptosis (49.7%, 72 h) could not be inhibited thoroughly by GW9662 (36.2%, control:3.2%). It indicated that the CGZ-induced cell apoptosis was partially PPARgamma-independent. Western blotting showed a cleavage of caspase-3 zymogen protein and up-regulation of p P38 protein. Thus it indicated that the activations of caspase-3 and P38 MAPK were involved in CGZ-induced cell apoptosis. CONCLUSION: CGZ inhibits cell growth by induction of cell apoptosis in HL-60 cells via PPARgamma dependent and independent signaling pathways. The activations of caspase-3 and P38 MAPK may be one of the important mechanisms in CGZ in treated HL-60 cells. PMID- 21029676 TI - [Potential effect of uremic medium on cell proliferation and apoptosis and the activation of nuclear factor-kappa B pathway of aortic endothelial cells in rabbit culture]. AB - OBJECTIVE: To investigate the potential effect of uremic medium on cell proliferation and apoptosis of aortic endothelial cell (AEC), two key processes in the development of atherosclerosis, in rabbit culture. And to understand the effects of uremic medium on the activation of nuclear factor-kappa B (NF-kappaB) pathway and cytokines expression of AEC. METHODS: Rabbit AEC were cultured with growth media supplemented with pooled sera from normal rabbits or those with chronic renal failure. The 80% confluent AEC were incubated for 24 h with media supplemented with pools of control or uremic sera. Cell proliferation was assessed by a MTT assay and cell cycle detected by flow cytometry. Hoechst33342 assay and flow cytometry were used to investigate the apoptotic effect of uremic medium in AEC. The expression of mRNA and protein levels for NF-kappaB, IkappaBalpha were analyzed by reverse transcription-polymerase chain reaction (RT PCR) and Western blot. NF-kappaB P65 nuclear translocation was analyzed by immunofluorescence. The activity of NF-kappaB was measured by electrophoretic mobility shift assay (EMSA). Concentrations of TNF-alpha and IL-6 in culture supernatants were evaluated by ELISA, and the expression of protein for TNF-alpha in cell lysates by Western blot. RESULTS: Uremic medium induced proliferation in the lower concentration range of 3%-10% while promoted apoptosis in the higher concentrations (> 10%). Uremic serum increased NF-kappaB mRNA (0.35 +/- 0.05 vs 0.26 +/- 0.02, P < 0.01) and protein (1.67 +/- 0.15 vs 0.41 +/- 0.05, P < 0.01) expression, decreased IkappaBalpha mRNA (0.13 +/- 0.03 vs 0.24 +/- 0.04, P < 0.01) and protein (0.29 +/- 0.06 vs 0.65 +/- 0.08, P < 0.01) expression. Uremic serum enabled NF-kappaB p65 nuclear translocation and increased NF-kappaB DNA binding activity. An increased secretion of cytokines IL-6 and TNF-alpha. in AEC was observed after a treatment of 10% uremic sera in a time dependent manner. The expression of TNF-alpha in AEC exposed to 10% uremic sera also increased significantly (0.37 +/- 0.04 vs 0.14 +/- 0.03, P < 0.01). CONCLUSION: Uremic medium induces the activation of AEC. A lower level of uremic medium accelerates the proliferation of AEC while a higher level induces the apoptosis of AEC. The increased proliferation may be related to a higher NF-kappaB activity and the expression of inflammation cytokines. Although the enhanced atherosclerosis can not be explained on the basis of an apoptotic process, the proliferative status can contribute to intimal proliferation, an earlier step in the development of atherosclerosis. PMID- 21029677 TI - [Effect of pioglitazone on receptor activator of nuclear factor-kappa B expression in osteoclast from RAW264.7 cells]. AB - OBJECTIVE: To study the effect of pioglitazone, a synthetic peroxisome proliferator-activated receptor gamma (PPARgamma) agonist, on the RANKL-mediated osteoclastogenesis of osteoclast precursor cells, and to explore the function and mechanism of PPARgamma in the osteoclast differentiation. METHODS: Pioglitazone treatment of RAW264.7 murine macrophages were compared with those of simply cultured control and RANKL-mediated control. Accordingly, the RANKL-mediated cells were cultured with 30 ng/ml RANKL, then induced into significant multinuclear osteoclast formation. And pioglitazone treated cells were exposed to 10 umol/L pioglitazone during the process of osteoclast differentiation under RANKL. The number of mature osteoclasts was calculated and the mRNA levels of RANK analyzed by real-time quantitative PCR. RESULTS: Pioglitazone significantly inhibited osteoclastogenesis of osteoclast precursor cells, the number of mature osteoclasts of pioglitazone treated group was (176 +/- 58)/cm(2) and significantly less than the mature cells of RANKL induced group which number was (322 +/- 74)/cm(2) (P < 0.01); and pioglitazone also significantly inhibited the mRNA expression of RANK, a typical differentiated factor of osteoclast, the number of the mRNA expression of RANK of pioglitazone treated group was 2.16 +/- 0.74 and significantly less than the number of RANKL induced group (4.94 +/- 0.39, P < 0.01). CONCLUSION: PPARgamma agonist inhibited the differentiation of RAW264.7 towards osteoclast. It might be due to the suppression of RANK gene expression in the process of osteoclast differentiation. PMID- 21029678 TI - [Expediting the study on the role of stem cells in wound treatment]. AB - The restoration of destroyed skin tissue in extensive deep burn injury has been perplexing burn surgeons for a long time due to impossibility of de novo formation of true skin in the process of burn wound healing with the current treatment methods. Stem cells possess the capacity to repair the damaged tissue through regeneration of the original structure and function, and it is considered as the expected ideal outcome of burn wound healing and also the final goal of multidisciplinary wound managements. In the skin tissue, the resident stem cells do exist, and they retain an autonomous self-renewal potential, and they respond to guiding signals to differentiate in repairing burn wound. Besides, the remote mesenchymal stem cells and the adjacent adipose-derived stem cells have been shown to be involved in burn wound healing. The basic studies demonstrated that the microenvironmental feature or extracellular regulators, the selective activation of intracellular signaling pathways, and the expression of specific genes have a significant influence on the proliferation, differentiation or function of stem cells in wound repair. Therefore, further investigation and manipulation of the molecular mechanisms by which stem cells could participate well in regenerating skin tissue would be a valuable and promising way in burn wound treatment. The recent discovery of reprogramming a mature body cell into a pluripotent stem cell, which can then be converted to any type of human body cell sheds a new light to regenerative medicine. Stem cell-based regeneration is offering the next coming frontier of medical therapy by yielding new treatment through delivery of pluripotent stem cells to achieve structural and functional repair in the damaged tissues or organs due to trauma or chronic diseases. Therefore, it is a pressing task for us to expedite the study on the role and utility of stem cells in burn wound treatment, especially aiming to explore the possibility in regenerating skin appendages or even the entire structure of the normal skin, and avoiding the formation of hypertrophic scar or chronic wound after burn. PMID- 21029679 TI - [Repair of scars in submaxillary region using expanded forehead axial flaps with fascia pedicles carrying bilateral frontal branches of superficial temporal artery and vein]. AB - OBJECTIVE: To study the feasibility of applying expanded forehead axial flaps with fascia pedicles carrying bilateral frontal branches of superficial temporal artery and vein (expanded forehead axial flap with double pedicles in brief, EFAF DP) in repairing scars in submaxillary region. METHODS: Sixteen patients with mandibular scars hospitalized in Department of Burns and Plastic Surgery of the First Hospital Affiliated to Fuzhou General Hospital in Nanjing Military Area Command from July 2005 to December 2009 were repaired with EFAF-DP. The operation consisted of 3 stages. Before operation, the location and course of superficial temporal arteries and veins (STAV) and their frontal and parietal branches were identified with Ultrasonic Doppler blood flow detector. In stage I, STAV were dissected from the frontalis muscle as a pedicle to form a skin soft tissue space to hold the dilator of a proper size. In stage II, after gradual dilation by repeated filling with saline, the dilator was removed. EFAF-DP was dissected to repair mandibular scar. Donor site was closed with sutures. In stage III, flap pedicles were divided and pruned. RESULTS: Flap sizes ranged from 25 cm * 6 cm to 33 cm * 16 cm. The duration of dilation was 3-5 months, with 3.6 months in average. Ten patients underwent the operation of EFAF-DP transplantation and cervical skin dilatation. All flaps survived with healing of wounds. Disorder of venous return at the distal end of one flap was seen after second stage surgery, and it was corrected after comprehensive treatment including relieving spasm and improving venous return. Donor site wounds healed with normally grown hair without cicatricial alopecia along the hairline. Few hairs grew around mandible in one female patient out of the three (no hair grew on flaps of other two patients). This female patient and two male patients requesting for beard plasty received laser depilation treatment 1 to 3 months after discharge, with good result. Other male patients received no special treatment for their beard, and they shaped their beard with shaver. Sixteen patients were followed up for 6 to 24 months, and the shape of the flaps and beard (excluding female patients) were satisfactory with good appearance, satisfactory skin color and texture. The mobility of neck was obviously improved. CONCLUSIONS: EFAF-DP provides bigger areas of a thin flap besides promoting vascularization of new vessels of flap. Extra expanded skin can be directly sutured at the fringe of hairline, which makes skin grafting unnecessary, and decreases the incidence of secondary deformity in donor sites. Some hair carried by the flaps can be directly used for beard reconstruction after rotation to help the male patients have a better appearance. PMID- 21029680 TI - [Repair of devastating wounds with free composite tissue flap]. AB - OBJECTIVE: To study the safety and effects of free composite tissue flaps in repairing devastating wounds in early stage. METHODS: One hundred and twenty three patients with 128 devastating wounds hospitalized in our burns center from 2005 to 2009 were repaired with free flaps or composite tissue flaps. Flap types used included 58 latissimus dorsi muscular flaps, 32 anterolateral thigh flaps, 21 circumflex scapular flaps, 6 dorsalis pedis composite flaps, 3 big toe nail skin flaps, 3 forearm flaps, and 1 lateral thoracic flap. One wound was repaired with lateral lower leg flap with fibula, and 3 wounds with free latissimus dorsi muscular flap plus skin graft. RESULTS: Vascular crisis was observed in 10 transplanted flaps 1 to 5 days after operation; 6 flaps with this complication were saved after emergency surgical exploration. Total survival rate of transplanted flaps and composite tissue flaps was 95.3% (122/128). All patients were followed up for 3 months to 4 years; satisfactory appearance and restoration of partial function were found in all of them. CONCLUSIONS: Free composite tissue transplantation reduces amputation rate, achieves primary reconstruction of function with good appearance, shortens length of hospital stay, and reduces surgical operation time, complications, and treatment cost. It is a good approach in the repair of massive devastating soft tissue injury. PMID- 21029681 TI - [Repair of wounds in popliteal fossa scar with perforator flaps of gastrocnemius medial head]. AB - OBJECTIVE: To study the effect of perforator flaps of medial head of gastrocnemius muscle on repairing popliteal fossa scar wounds. METHODS: Ten patients with scar in popliteal fossa hospitalized from January 2005 to January 2010 were repaired with perforator flaps of medial head of gastrocnemius muscle. The scar was resulted from burn in 8 patients, and from operation in 2. The duration of the scar was 3 months to 11 years, and area of the scar ranging from 6 cm * 3 cm to 10 cm * 6 cm. Ultrasonic Doppler was used to detect the musculocutaneous perforator vessel of the medial sural artery at the position 10 to 17 cm from the fold of the popliteal fossa and 2 to 5 cm from the posterior midline before surgery. Then flap transplantation surgery was performed. Donor site wounds with width less than 5 cm were sutured directly, and those wider than 5 cm were repaired with skin transplantation. RESULTS: All the flaps survived. Flap size ranged from 7 cm * 5 cm to 12 cm * 7 cm. All patients were followed up for 3 to 30 months, and the flaps were found to have a good appearance. Patients could walk with heavy load without lameness. The function of knee joint of the affected limb was the same as that of the opposite limb. No obvious depression was observed in donor sites. CONCLUSIONS: The perforator flaps of medial head of gastrocnemius muscle can be used to repair the popliteal fossa scar wound with satisfactory result. PMID- 21029682 TI - [Microsurgical repair of skin and soft tissue defects on head, face, and neck]. AB - OBJECTIVE: To study the microsurgical method of repairing skin and soft tissue defects on head, face, and neck. METHODS: Thirty-one patients with skin and soft tissue defects on the head, face, or neck were hospitalized from July 2007 to May 2010, including 10 cases of scalp defects, 4 cases of skin and soft tissue defects on face, and 17 cases of skin and soft tissue defects on neck. Among them, the cause in 20 cases was trauma, and in 11 cases they were secondary to release of cicatricial contraction. Free flaps were transplanted to repair the wounds, including 13 latissimus dorsi flaps, 3 lateral thoracic flaps, 5 scapular flaps, and 10 anterolateral thigh flaps. The area of flaps ranged from 8 cm * 5 cm to 25 cm * 18 cm. RESULTS: All flaps survived, and all the wounds healed by first intention. The average length of hospital stay was 16.7 days. Twenty-eight patients were followed up for 2 months, and in all of them satisfactory function and appearance were restored. CONCLUSIONS: Free flap graft based on microsurgery can repair wound of skin and soft tissue defects on head, face and neck by a single operation, which eases suffering of patients, and shortens the length of hospital stay. PMID- 21029683 TI - [Anatomic basis of the accompanying pattern of the superficial temporal arterial branches and veins and its clinical application]. AB - OBJECTIVE: To study the course of branches of the superficial temporal artery (BSTA) and the accompanying pattern of their veins in order to provide anatomic basis for flap design. METHODS: Head and facial part of ten adult corpses (19 sides) were dissected and photographed. The coordinate system was set up with external auditory foramen as the point of origin, aided by the graph analysis software Digimizer. The course of the frontal branch and parietal branch of the superficial temporal artery (STA), and the accompanying pattern between the BSTA and the veins were measured and analyzed. The STA and its branches were located by Ultrasonic Doppler, and the corresponding branches of the superficial temporal vein (BSTV) were disclosed by bowing patient's head with breath holding or cerclaging the basement of the patient's skull. And then 10 sides of transposition (fascia) flaps with axis at the angular bisector between BSTA and BSTV were devised to repair wounds of 9 patients that hospitalized from February 2008 to December 2009. Data were processed with test of variance homogeneity. RESULTS: Frontal BSTV absence was found in 6 head sides, and the maximum distance between artery and vein was (2.1 +/- 1.2) cm. Parietal BSTV absence was found in 3 head sides, and the maximum distance was (1.4 +/- 0.7) cm. The distance between frontal BSTA and BSTV was larger than that between parietal BSTA and BSTV, and the dispersion degree of the former was higher than that of the latter (F = 0.0404, P = 0.0475). All the (fascia) flaps survived without congestion or necrosis. CONCLUSIONS: When branch of the superficial temporal vessel was selected as the axial vessel of flap, the flap design shall depend on the accompanying pattern of BSTV to avoid the flap necrosis due to poor venous return after surgery. The superficial temporal vein and its branches can be well disclosed by bowing head or cerclaging skull. The approach is simple, useful, safe, and reliable. PMID- 21029684 TI - [Diagnosis of the deep partial-thickness burn wound of Skh-1 mouse with Optical Coherence Tomography]. AB - OBJECTIVE: To evaluate the application value of Optical Coherence Tomography (OCT) in the diagnosis of the depth of burn wound. METHODS: Deep partial thickness scald models of Skh-1 mice were reproduced using self-made steam scald appliance. The scald wounds were scanned with OCT 3 hours, or 3 and 8 days after injury respectively. Scanned wound tissue was harvested for histological examination right after each episode of OCT imaging. Normal skin of mice was scanned and examined with the above-mentioned methods at the same time. RESULTS: Compared with those of the normal skin, collagen in the dermis was denatured after steam scald, and it was imaged as vanishing or reduction in birefringence in OCT detection. The structure change intensity was related to the pathological process of the wounds and consistent with the corresponding histological results. CONCLUSIONS: OCT is a noninvasive technique. It can be used to diagnose the depth of burn wound in real time. PMID- 21029685 TI - [Distribution and vicissitude of drug resistance of Acinetobacter baumannii in burn intensive care unit of Wuhan City Hospital No.3 in three years]. AB - OBJECTIVE: To study the clinical distribution characteristics and vicissitude of antibiotic resistance of Acinetobacter baumannii (AB), and to look for the risk factors of AB infection in order to provide reasonable reference for the prevention and treatment of its infection. METHODS: Specimens of blood, venous catheters, sputum, wound exudates and pharyngeal swabs from 156 patients hospitalized in our burn ICU from January 2006 to December 2008 were collected and cultured. The clinical distribution and antibiotic resistance of AB were determined and analyzed. The risk factors related to AB infection were analyzed. Drug resistance rate data were processed with WHONET 5.3 software; the other data were processed with chi-square test and Logistic regression analysis. RESULTS: Ninety-two strains of AB were identified during the three years from different kinds of specimens, with 41 (44.6%) from wound exudates, 14 (15.2%) from pharyngeal swabs and sputum respectively, 13 (14.1%) from blood, and 10 (10.9%) from venous catheters. AB accounted for 23.1% (30/130), 27.5% (25/91), 28.2% (37/131) respectively among the strains detected in 2006, 2007, and 2008. During the three years, except for imipenem and cefoperazone/sulbactam, the average resistance rates of AB to other ten commonly used antibiotics were all above 50.0%. Burn area (chi(2) = 24.374, P = 0.000), mechanical ventilation (chi(2) = 8.968, P = 0.003), duration of use of antibiotics (chi(2) = 3.981, P = 0.046), and deep venous catheterization (chi(2) = 9.170, P = 0.002) were the risk factors of AB infection, and the former two were independent risk factors. CONCLUSIONS: There is a pan-drug resistance tendency of AB in our burn ICU, and the positive culture rates are increasing in recent years. Disinfection and isolation measures, appropriate use of antibiotics, avoidance of invasive performances such as deep venous catheterization and tracheostomy, or shortening their duration are important means to prevent and control infection of AB. PMID- 21029686 TI - [Comparing the effect of high frequency oscillatory ventilation and conventional mandatory ventilation on the myocardial function of rabbit with inhalation injury]. AB - OBJECTIVE: To compare the effect of high frequency oscillatory ventilation (HFOV) and conventional mandatory ventilation (CMV) on the myocardial function of rabbits with inhalation injury. METHODS: Steam inhalation injury model was reproduced in 16 New Zealand albino rabbits. They were randomly divided into CMV group (n = 8) and HFOV group (n = 8) by drawing lots, and they received ventilation in metered volume and HFOV treatment respectively. Heart blood was drawn from rabbits before they were sacrificed 4 hours after treatment to determine the plasma activity of lactate dehydrogenase 1 (LDH1) and creatine phosphorylated kinase (CPK-MB). Myocardial tissue from left ventricle was harvested and homogenized to determine the concentration of TNF-alpha and IL-8, the activity of caspase-1, and the activity of myosin-light-chain kinase (MLCK) and the ATPase of myosin light chain (MLC-ATPase) by enzyme-linked immunosorbent assay, spectrophotometry, and the nuclide liquid scintillation technique respectively. Part of the myocardial tissue sample was examined pathologically. Data were processed with analysis of variance. RESULTS: (1) The activities of LDH1 and CPK-MB in plasma were obviously higher in CMV group than in HFOV group [(643 +/- 108), (342 +/- 48) U vs. (233 +/- 92), (186 +/- 36) U, with F value respectively 10.326 and 9.846, P values all below 0.01]. (2) The contents of TNF alpha, IL-8 and the activity of caspase-1 in myocardial tissue homogenate were obviously higher in CMV group than in HFOV group [(181 +/- 35), (89 +/- 19) pg/g, and (0.56 +/- 0.27) g/g protein vs. (94 +/- 21), (43 +/- 11) pg/g, and (0.24 +/- 0.12) g/g protein, with F value respectively 8.239, 7.826, 5.716, P values all below 0.01]. (3) The activities of MLC-ATPase and MLCK were lower in CMV group than in HFOV group [(0.24 +/- 0.12) umol*mg(-1)*min(-1), (3.3 +/- 1.1) mmol*mg( 1)*min(-1) vs. (0.48 +/- 0.16) umol*mg(-1)*min(-1), (7.7 +/- 1.7) mmol*mg( 1)*min(-1), with F value respectively 4.125, 4.766, P values all below 0.01]. (4) No obvious necrosis, degeneration or inflammatory cell infiltration was observed in myocardial tissue of rabbits in 2 groups under light microscope; but the myocardial fiber was slightly swollen, and it was less marked in the HFOV group. CONCLUSIONS: The influence of HFOV on myocardial myosin phosphorylation system of rabbits with inhalation injury is less than that of CMV. PMID- 21029687 TI - [Effect of platelet-derived growth factor-BB on the healing and adhesion of rat tendon]. AB - OBJECTIVE: To study the effect of platelet-derived growth factor-BB (PDGF-BB) gene transfected rat tendon cells on the healing and adhesion of rat tendon. METHODS: A model of heel tendon injury was reproduced in 90 rats. They were randomly divided into three groups: experiment group [with injection of 20 uL rat tendon cells (1 * 10(8) cell/mL) transfected with PDGF-BB gene into the injured tendon ends], control group [with injection of 20 uL non-transfected rat tendon cells (1 * 10(8) cell/mL) into the injured tendon ends], and blank control group (without treatment), with 30 rats in each group. Heel tendon ends were sutured with 6-0 thread by modified Kessler method and immobilized with tube-type plaster of Paris cast for one week. Rat tendon cells transfected with PDGF-BB gene were identified with gene sequencing and RT-PCR. Tendon tissue sample was harvested 3 days or 1, 2, 4, 8 week(s) after operation (POD or POW) for morphology and histology observation, and bio-mechanical test. The degree of tendon adhesion, the number of Fb and collagen fiber content in tissue, maximum tensile strength and sliding distance of tendon, and concentration of PDGF-BB in tendon tissue among groups were compared. Data were processed with t test. RESULTS: (1) PDGF-BB mRNA expressed stably in PDGF-BB gene transfected tendon cells as testified by RT PCR and gene sequencing. (2) Obvious edema and inflammatory cells infiltration were observed in each group on POD 3, but they were less pronounced in experiment group. And the changes in all groups were ameliorated gradually. The difference in grading of tendon adhesion was not obvious among groups in POW 4 and 8. (3) Fb number in experiment group in POW 2, 4, 8 was respectively fewer than that of control group and blank control group (with t value respectively 2.94, 4.26, 5.76 and 4.00, 3.83, 6.12, P < 0.05 or P < 0.01). (4) Collagen fiber content in rat tendon of experimental group in POW 4 was (43 +/- 6)%, which was significantly lower as compared with that of control group [(55 +/- 8)%] and blank control group [(61 +/- 8)%] (with t value respectively 2.94 and 4.41, P < 0.05 or P < 0.01). (5) The largest sliding distance of tendon in experiment group in POW 4 and 8 were (3.25 +/- 0.33) and (3.65 +/- 0.21) mm, which were significantly longer than those in control group [(2.29 +/- 0.40), (2.21 +/- 0.37) mm] and blank control group [(2.01 +/- 0.23), (1.89 +/- 0.24) mm] (with t value respectively 4.53, 8.29 and 7.55, 13.52, P values all below 0.01). There was no statistical significant difference among the three groups in the maximum tensile strength of tendon (with t value respectively 0.41, 0.41, 0.77, 0.72, P values all above 0.05). (6) Content of PDGF-BB in tendon tissue of experimental group on POD 3 and in POW 2, 4 were (12.95 +/- 1.36), (8.32 +/- 0.94), (9.10 +/- 1.06) ng/mL, all significantly higher than those in control group [(1.13 +/- 0.21), (2.07 +/- 0.48), (3.85 +/- 0.39) ng/mL] (with t value respectively 21.04, 14.50, 11.39, P values all below 0.01). CONCLUSIONS: PDGF-BB gene transfected rat tendon cells can promote endogenous healing of tendon and prevent tendon adhesion. PMID- 21029688 TI - [Generation mechanisms and management strategies of adverse reactions to Bevacizumab during cancer treatment]. PMID- 21029689 TI - [Gene therapy based on inducible IL-12 gene in a mouse model of orthotopically transplanted H22 hepatoma]. AB - OBJECTIVE: To evaluate the antitumor efficiency of IL-12 gene induced by RU486 regulatory system in a mouse model of orthotopically transplanted hepatoma. METHODS: The orthotopic hepatoma model was prepared by inoculation of H22 hepatoma cells into the mouse liver. Murine interleukin-12 (IL-12) expressing plasmid pRS22 containing RU486 regulatory system was injected into mice by a hydrodynamic injection 3 days after H22 cells inoculation. Three days after hydrodynamic injection, the mice were induced with RU486 (250 ug/kg) consecutive intraperitoneal administration for 6 days. Blood samples were taken at 10 h after the first and third induction for the determination of IL-12, IFN-gamma and NO. Five mice were sacrificed at 2 days after the treatment with RU486. The tumor size was measured. HE and immunohistochemical stainings were applied to evaluate the proliferative activity and angiogenesis in the tumors. The other 7 mice were kept to monitor their survival. RESULTS: In mice receiving saline plus RU486, pRS LacZ plus RU486, or pRS22 plus sesame oil, the liver tumors were big in size: (409.90 +/- 137.03) mm(3), (271.80 +/- 182.63) mm(3) and (251.00 +/- 76.55) mm(3), respectively. Strong PCNA positive expression [(82.10 +/- 4.62)%, (83.45 +/- 2.34)% and (77.46 +/- 2.99)%] and extensive microvessel density (74.58 +/- 18.47, 63.60 +/- 13.36 and 53.52 +/- 11.74 per 400 * field), respectively, in these tumor tissues were observed after immunohistochemical staining. The survival period was shorter in these mice. In contrast, in mice treated with pRS22 plus RU486, the tumor was smaller in size. Extensive necrosis, weak PCNA proliferative activity (50.67 +/- 8.09)%, and a marked paucity of microvessel density (25.38 +/- 10.87) were seen. The survival of mice was obviously prolonged. Compared with the 3 control groups, a significant elevation of serum IL-12, IFN-gamma and NO levels were detected in the mice treated with pRS22 plus RU486. CONCLUSION: Expression of IL-12 gene can be effectively controlled by a RU486 regulatory system. The inducible IL-12 can delay the growth of orthotopically transplanted hepatoma and prolong the survival of mice. PMID- 21029690 TI - [Association between HPV infection and HLA-DQB1 alleles polymorphism in the cervical carcinogenesis in Uyghur women in southern Xinjiang]. AB - OBJECTIVE: To investigate the association between HPV infection and HLA-DQB1 alleles polymorphism in the cervical carcinogenesis in Uyghur women in southern Xinjiang. METHODS: Twenty-one subtypes of HPV and the 5 alleles of HLA-DQB1 were detected from cervical tissues of 190 cervical cancer cases and 190 normal subjects by flow-through hybridization and gene chip (HybriMax) assay and polymerase chain reaction sequence-specific oligonucleotide technique (PCR-SSO). RESULTS: (1) The positive rate of HPV in cervical cancer and control groups were 70.0% and 8.9%, respectively. HPV16 was the most common type in HPV positive cervical cancer patients with a rate of 64.7%, followed by HPV18 (2.6%), HPV68 (2.1%), HPV45 (1.6%), HPV58 (1.6%), HPV39 (1.6%), HPV31 (1.1%), HPV56 (1.1%), HPV59 (0.5%), HPV53 (0.5%) and HPV6 (0.5%), respectively. The positive rates of HPV and HPV16 in the cervical cancer group were significantly higher than that in the control group. (2) The frequency of HLA-DQB1*03 was significantly lower than that in the control group (OR = 0.683, 95%CI = 0.505 - 0.923). The frequency of other HLA alleles had no significant differences between the cervical cancer group and the control group. (3) In the cervical cancer group, the frequency of HLA-DQB1*06 in both HPV positive and HPV16 positive cases were significantly higher than that in both the HPV and HPV16 negative cases. CONCLUSION: HPV16 is the most common type in both the cervical cancer and control groups. It appears that HLA-DQB1*03 may be a protective gene in the cervical carcinogenesis in southern Xinjiang Uyghur women, and the HLA-DQB1*06 is a susceptibility gene to HPV/HPV16 infection in Uyghur women. The study of HLA alleles in the cervical carcinogenesis in Uyghur women may play an important role in the intervention research of cervical cancer. PMID- 21029691 TI - [Pro-apoptotic effect on osteosarcoma SOSP-9607 cells by human recombinant caspase-6 fusion protein]. AB - OBJECTIVE: To investigate the pro-apoptotic effect of Her-2 targeted recombinant caspase-6 fusion protein on osteosarcoma SOSP-9607 cells. METHODS: Recombinant immunocasp-6 was generated by sequential fusion of the genes of a signal peptide, a single-chain Her-2 antibody (e23sFv), a PEA translocation domain (PEA aa253 364) and an active caspase-6. The immunocasp-6 gene was cloned into pCMV plasmid to construct a kind of eukaryotic expression vector, i.e. pCMV-e23sfv-PE II caspase-6 (abbr. pCMV-6) and transfected into SOSP-9607 cells. Murine xenograft models were randomly divided into two groups that received i.m. injections of liposome encapsulated pCMV-6 or pCMV alone. The tumor volume and weight of the nude mice and the tumor weight of the cured mice were observed and statistically analyzed. The morphological changes of the tumors were examined with HE staining, apoptotic morphology of the tumor was observed by TUNEL staining and the gene expression was analyzed by immunohistochemical staining. RESULTS: The tumor growth of the mice in the treatment group was significantly slower than that of the control group (P = 0.001). The weight of the nude mice in the treatment group was significantly higher than that of the control group (P = 0.0002). The tumor weight of the mice in the treatment group was significantly lower than that of the control group (P = 0.0006). HE and TUNEL staining of the tumor of nude mice in the treatment groups showed typical characteristics of apoptosis, while normal structure was found in the control group. Furthermore, caspase-6 was not found in the tumor and muscle tissues in the control group, but only in the treatment group by immunohistochemistry. CONCLUSION: Immunocasp-6 can selectively recognize and bind to and kill HER-2 positive osteosarcoma cells, therefore, to offer some foundation for the clinical treatment of osteosarcoma. PMID- 21029692 TI - [Helicobacter pylori cytotoxin associated protein CagA regulates gastrin gene promoter activity]. AB - OBJECTIVE: To study the regulatory effect of Helicobacter pylori CagA protein on gastrin promoter and the related signaling pathways as to further elucidate the mechanism of the development and progression of human gastric carcinoma. METHODS: After pcDNA3.1ZEO(-)/CagAand PGL/GP were identified by double restriction enzyme digestion, PCR and sequencing, the gastric cancer cell lines AGS and SGC-7901 cells were co-transfected with pcDNA3.1ZEO(-)/CagA and PGL/GP for 48 h. Alternatively, AGS and SGC-7901 cells were transfected by PGL/GP for 36 h later, and infected with Helicobacter pylori for additional 12 h. Meanwhile, the transfected and infected cells were treated using the JAK2 signaling pathway inhibitor AG490 and the ERK signaling pathway inhibitor U0126. The untreated cells and empty-vector-transfected cells were used as the control. Finally, luciferase activity was detected using the luciferase reporter assay system in transfected and infected cells. The levels of gastrin mRNA was determined by TaqMan(r) real-time quantitative PCR. RESULTS: After co-transfection with pcDNA3.1ZEO(-)/CagA and PGL/GP, the activities of luciferase were increased by 251.3, 106.1 and 2.4 times in AGS cells and 35.8, 22.7 and 13.4 times in SGC-7901 cells, respectively, as compared with that of the control, pcDNA3.1 ZEO(-)/CagA + PGL3/Basic and pcDNA3.1 ZEO(-) + PGL/GP groups. The activities of luciferase in PGL/GP transfection and HP infection group were also increased by 1673.2, 33.5, 1.4 times in AGS cells and 1180.2, 72.2 and 1.5 times in SGC-7901 cells, respectively, as compared with that of the control, PGL3/Basic + HP and PGL/GP groups. There were statistically significant differences between them (P < 0.05), which suggested that the transcription activity of gastrin promoter increased significantly. But after adding the inhibitor AG490 and U0126, respectively, the activities of luciferase were significantly decreased by 95.7% (U0126) and 33.0% (AG490) in co-transfected AGS cells and 94.8% (U0126) and 86.2% (AG490) in co transfected SGC-7901 cells with pcDNA3.1ZEO(-)/CagA and PGL/GP (P < 0.05). In the PGL/GP transfection and HP infection group, the activities of luciferase were significantly decreased by 24.6% (U0126) and 25.8% (AG490) in AGS cells and 57.3% (U0126) and 14.1% (AG490) after adding the inhibitor AG490 and U0126, respectively (P < 0.05). The results showed that the gastrin promoter activities were significantly inhibited. The gastrin mRNA levels were 3.0 and 4.5 times higher in HP-infected AGS and SGC-7901 cells, respectively, than that in the control groups. In the cells transfected with pcDNA3.1ZEO(-)/CagA, the gastrin mRNA levels were raised 10.8 and 2.3 times (AGS cells) and 10.9 and 16.2 times (SGC-7901 cells), respectively, as compared with that of control and pcDNA3.1ZEO( ) groups. All of the differences were statistically significant (P < 0.05). CONCLUSION: These results suggest that CagA may activate the gastrin promoter and up-regulate the expression of gastrin gene, and CagA is one of the important proteins in regulating gastrin gene expression. The ERK/MAPK and JAK/STAT signaling pathways may be involved in the controlling of gastrin gene expression by CagA. PMID- 21029693 TI - [Uptake of 2-NBDG by human breast cancer cells in vitro]. AB - OBJECTIVE: The purpose of this study was to assess the feasibility of fluorescent 2-deoxyglucose analog, 2-[N-(7-nitrobenz-2-oxa-1, 3-diaxol-4-yl)amino]-2 deoxyglucose (2-NBDG), that could be taken up by breast cancer cells highly expressing glucose transporter 1 (GLUT-1). The purpose of this study was to clarify if a fluorescent 2-deoxyglucose analog, 2-[N-(7-nitrobenz-2-oxa-1, 3 diaxol-4-yl)amino]-2-deoxyglucose (2-NBDG), can be taken up by breast cancer cells highly expressing glucose transporter 1 (GLUT-1), and to assess whether it can be used as a targeting imaging agent. METHODS: The expressions of GLUT-1 mRNA and protein in breast cancer MDA-MB-231 cells were detected by RT-PCR and immunohistochemistry, respectively. The difference of GLUT-1 protein expression between breast cancer MDA-MB-231 cells and MCF-7 cells was compared by Western blot. Secondly, MDA-MB-231 cells which were grown in 6-well plates were incubated with 2-NBDG, and the result of 2-NBDG uptake was analyzed by fluorescence microscopy and flow cytometry. The difference of 2-NBDG absorption in MDA-MB-231 and MCF-7 cells was compared by flow cytometry. RESULTS: The results of RT-PCR and immunohistochemistry confirmed that MDA-MB-231 cells highly expressed GLUT-1. Furthermore, Western blot revealed that GLUT-1 expression of MDA-MB-231 cells (0.946 +/- 0.007) was higher than that in the MCF-7 cells (0.833 +/- 0.010). Fluorescence microscopic and flow cytometric analysis showed that 2-NBDG was uptaken rapidly by MDA-MB-231 cells. Addition of 50 mmol/L D-glucose to the media with 2-NBDG reduced its uptake by 46.0%. Moreover, flow cytometry indicated that the fluorescence intensity of MDA-MB-231 cells (25.10 +/- 0.57) was higher than that of MCF-7 cells (10.12 +/- 0.62) when incubated with 2-NBDG for 20 minutes. CONCLUSION: The preliminary data clearly demonstrate that 2-NBDG is taken up and accumulated in breast cancer cells that highly express GLUT-1, and may be used as an optical probe for glucose uptake in hypermetabolic malignant cells. PMID- 21029694 TI - [Different influence of Her-2 expression on the prognosis in node-positive and node-negative breast cancer]. AB - OBJECTIVE: To investigate the prognostic significance of Her-2 expression in node positive and node-negative breast cancer in Chinese women. METHODS: The Her-2 expression in breast cancers from 981 patients was detected by immunohistochemistry with anti-Her-2 (CB11) monoclonal antibody. The survival curves were analyzed by Kaplan-Meier method, and Cox regression model was applied to determine whether this factor is an independent predictor of survival in multivariate analysis. RESULTS: Nineteen point seven percent of the patients showed positive Her-2 expression in their tumors. Patients with Her-2-positive tumors tended to be younger. The high level Her-2 expression was significantly associated with negative estrogen receptor and progesterone receptor status in their tumors (P < 0.05). Among 387 patients with node-positive disease, the 5 year disease-free survival (DFS) rate and 5-year overall survival (OS) rate were significantly lower in patients with Her-2-positive tumors than in patients with Her-2-negative tumors (DFS: 48.8% vs. 66.9%, P = 0.009; OS: 55.2% vs. 76.4%, P = 0.001), and Her-2 expression was an independent unfavorable prognostic factor for OS, but not for DFS in patients with node-positive disease. Among 591 patients with node-negative disease, Her-2 expression was not significantly associated with DFS and OS (P > 0.05). CONCLUSION: Her-2 expression is an important prognostic factor in patients with node-positive disease, but not for patients with node-negative disease in Chinese women. PMID- 21029695 TI - [Association between genetic polymorphisms of ERCC1, XRCC1, GSTP1 and survival of advanced gastric cancer patients treated with oxaliplatin/5-Fu-based chemotherapy]. AB - OBJECTIVE: To evaluate the association between the polymorphisms of excision repair cross complementation group 1 (ERCC1), X-ray repair cross complementing 1 (XRCC1), glutathione S-transferase Pi 1 (GSTP1) and the survival of advanced gastric cancer patients treated with oxaliplatin-based combination chemotherapy. METHODS: Eighty five patients with advanced gastric cancer accepted oxaliplatin/5 FU-based chemotherapy as first-line chemotherapy were investigated. Peripheral venous blood was taken before chemotherapy. DNA was extracted from peripheral venous blood. The genetic polymorphisms were detected by real-time PCR assay. The association between time to progression, overall survival and the polymorphisms was analyzed. RESULTS: The median time to progression of the 85 cases was 5.3 months, and the median overall survival was 8.0 months. ERCC1-118 C/C, XRCC1-399 G/G and GSTP1-105 A/G + G/G were favorable genotypes and the number of the favorable genotypes was associated with survival of the patients. The median overall survival was 12.5 months, 10.0 months, 6.5 months and 4.5 months for patients with 3 favorable genotypes, 2 favorable genotypes, 1 favorable genotype and none favorable genotype, respectively, with a significant difference (chi(2) = 35.54, P < 0.01). CONCLUSION: Genetic polymorphisms of ERCC1-118, XRCC1-399 and GSTP1-105 are associated with TTP and OS of advanced gastric cancer patients treated with oxaliplatin/5-Fu-based combination chemotherapy as the first-line chemotherapy. PMID- 21029696 TI - [Prognostic value of estrogen receptor, progesterone receptor and human epidermal growth factor receptor-2 in node positive breast cancer patients treated by mastectomy]. AB - OBJECTIVE: To evaluate the prognostic value of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (Her-2) in node-positive breast cancer patients treated by mastectomy. METHODS: The clinicopathological data of 835 breast cancer patients treated by mastectomy from January 2000 to December 2004 were retrospectively analyzed. All had positive axillary nodes without distant metastases and with the immunohistochemistry staining of ER, PR and Her-2 available. 764 (91.5%) patients received anthracycline- and/or taxanes-based chemotherapy. 464 (55.6%) patients received hormonal therapy. Eight (1%) patients received trastuzumab. Postmastectomy radiotherapy were given to 352 out of 437(80.5%)patients with T3-T4 and/or N2-N3 disease and 68 out of 398(20.9%)patients with T1-2N1 disease. Patients were classified into 4 subgroups according to the status of hormone receptors (ER and PR, Rec) and Her-2: Rec(-)/Her-2(-) (triple negative), Rec(-)/Her-2(+), Rec(+)/Her-2(+) and Rec(+)/Her-2(-). End points were isolated locoregional recurrence (LRR), distant metastases (DM), disease-free survival (DFS) and overall survival (OS). RESULTS: 141 (16.9%) patients were Rec(-)/Her-2(-), 99 (11.9%) Rec(-)/Her-2(+), 157 (18.8%) Rec(+)/Her-2(+) and 438 (52.5%) Rec(+)/Her 2(-). Patients with Rec(+)/Her-2(-) breast cancer had a significantly lower 5 year LRR rate than others (6.2% vs. 12.9%, P = 0.004). Compared with patients with Rec(+) breast cancer, patients with Rec(-) breast cancer had significantly higher 5-year DM rate (26.4% vs. 19.7%, P = 0.0008), lower DFS rate (66.7% vs. 75.6%, P = 0.0001) and lower OS rate (71.4% vs. 84.2%, P = 0.0000). In multivariate analysis, Rec(+)/Her-2(-) was significantly associated with lower risk of LRR. Rec(-) was an independent prognostic factor for higher risk of DM, decreased DFS and OS. CONCLUSION: ER, PR and Her-2 are independent prognostic factors for locoregional recurrence and survival in node-positive breast cancer patients treated by mastectomy. PMID- 21029697 TI - [Expression and significance of P311 and ITGB4BP in non-small cell lung cancer]. AB - OBJECTIVE: The aim of this study was to investigate the expression and significance of P311 and ITGB4BP in non-small cell lung cancer (NSCLC). METHODS: Tissue microarrays were prepared from 80 NSCLC specimens and examined by immunohistochemistry. RESULTS: The positive rates of P311 and ITGB4BP expression were 77.5% (62/80) and 82.5% (66/80), respectively. The double positive expression rate was 73.8% (59/80). The consistency rate was 87.5%, and there was a significant consistency between P311 and ITGB4BP expressions (Kappa = 0.611, P < 0.001). CONCLUSION: There may be a new signaling pathway P311-ITGB4BP in NSCLC, and it may regulate the lung cancer cell migration. PMID- 21029698 TI - [Relationship between P-glycoprotein function in peripheral blood cells and multidrug resistance in breast carcinoma]. AB - OBJECTIVE: To analyze the relationship between P-glycoprotein function in peripheral blood cells and primary multidrug resistance in breast carcinoma. METHODS: P-gp function was investigated by flow cytometry in NK cells of 16 breast cancer patients treated with anthracyclines and taxanes. Among all the patients, 8 were in chemotherapy-sensitive group and 8 in chemotherapy-resistant group. P-gp function was determined by rhodamine 123 (Rh123)-ejection test. Mathematical model was established by a regression of the fluorescence-time curve. The efflux rate constants of the chemotherapy-sensitive and -resistant groups were compared. RESULTS: There was no significant difference of Rh123 accumulation, retention or efflux between the two groups. The mathematical model of F(t) = F(0) . e(-kt) was established. K was the efflux rate constant, which was significantly different between the chemotherapy-sensitive and -resistant groups (P = 0.025). When k > 3.9 was used as diagnostic criterium for primary resistance, the sensitivity, specificity and accuracy were 75.0%, 100% and 87.5%, respectively. CONCLUSION: P-glycoprotein function in peripheral blood cells is associated with primary multidrug resistance in breast carcinoma. The efflux rate constant may be a good predictor for chemotherapy sensitivity. PMID- 21029699 TI - [Expressions of bFGF and PTEN in cervical carcinoma and their clinical significance]. AB - OBJECTIVE: To investigate the expressions of bFGF and PTEN in cervical carcinoma and their clinical significance. METHODS: Tissue microarray technique and immunohistochemistry SP method were used to detect the expressions of bFGF and PTEN in 143 cases of invasive carcinoma of cervix (ICC) and 20 cases of normal cervical epithelium remote from tumor (NCE). The relationship between the expressions of bFGF and PTEN in ICC and some factors relating to clinical pathology of cervical carcinoma such as histopathological grading, lymph node metastasis, stroma involvement and FIGO staging were analyzed. RESULTS: The rate of the positive expression of bFGF in ICC was significantly higher than that in NCE 88.8% (127/143) vs. 25.0% (5/20, P = 0.000). The rate of positive expression of PTEN in ICC was significantly lower than that in NCE 67.1% (96/143) vs. 100.0% (20/20, P = 0.000). The expression of bFGF was positively correlated with lymph node metastasis and histopathological grading (r = 0.239, P = 0.004 and r = 0.369, P = 0.000, respectively). The expression of PTEN was negatively correlated with FIGO staging, histopathological grading and lymph node metastasis (r = 0.189, P = 0.024; r = -0.211, P = 0.011; r = -0.321, P = 0.000, respectively). The expression of bFGF was negatively correlated with the expression of PTEN in ICC (r = -0.261, P = 0.002). CONCLUSION: The overexpression of bFGF and underexpression of PTEN are closely related to the invasion and growth of cervical carcinoma. Detection of the expression of both bFGF and PTEN may be of value in further understanding the biological behavior and predicting the prognosis of cervical carcinoma. PMID- 21029700 TI - [Value of dynamic contrast-enhanced MRI in assessment of early response to neoadjuvant chemotherapy in breast cancer]. AB - OBJECTIVE: To assess the value of dynamic contrast-enhanced MRI (DMRI) in predicting early response to neoadjuvant chemotherapy (NAC) in patients with locally advanced breast cancer (LABC) and to assess the accuracy of MRI in evaluation of residual disease after NAC. METHODS: Forty-three women with LABC (44 lesions, all were invasive ductal carcinoma) underwent DMRI before, after the first and final cycles of NAC. For each patient, the tumor volume, early enhancement ratio (E1), maximum enhancement ratio (Emax), and maximum enhancement time (Tmax), dynamic signal intensity-time curve were obtained during treatment. The residual tumor volumes obtained by DMRI were compared with pathological findings to assess the accuracy of DMRI. RESULTS: After the first cycle of NAC, the mean volume of responders decreased insignificantly (P = 0.055), but after NAC, mean volume of residual tumor decreased significantly (P = 0.000). Morphological changes: 29 cases showed a concentric shrinkage pattern while 7 cases showed a dendritic shrinkage pattern. Significant differences were found in E1, Emax and Tmax between responders and non-responders (P < 0.05). After the first cycle of NAC, E1, Emax and Tmax of responders changed significantly (P < 0.001), while there was no significant change in non-responders (P > 0.05). After NAC, the dynamic signal intensity-time types were changed in responders, and tended to be significantly flattening, while no significant change was found in non-responders. The residual tumor volume correlation coefficient between MRI and pathology measurements was very high (r = 0.866, P < 0.01). CONCLUSION: DMRI is useful to evaluate the early response to NAC in LABC. The presence and volume of residual tumor in LABC patients treated with NAC can be accurately evaluated by DMRI. PMID- 21029701 TI - [Efficacy and safety assessment of neoadjuvant paclitaxel and trastuzumab in Chinese women with Her-2 positive operable breast cancer]. AB - OBJECTIVE: To assess the efficacy and safety of neoadjuvant 3-weekly paclitaxel plus trastuzumab (TH) in Chinese women with Her-2 overexpressing operable breast cancer. METHODS: This is a single center open-label phase II clinical trial. The included patients underwent 4 cycles of neoadjuvant 3-weekly TH before surgery. The primary endpoint was pathologic complete response rate (pCR rate) and the secondary endpoint was overall response rate (OR rate). Patients were also stratified according to hormone receptor status, and pCR rate and OR rate were compared between subgroups. Adverse events were graded according to CTCAE v3.0. RESULTS: There were 40 eligible patients entering this study with median age of 49 years. All patients completed 4 cycles of neoadjuvant treatment. pCR rate was 52.5% and OR rate was 87.5%. The differences of pCR and OR rates between subgroups were of no statistical significance. No cardiac toxicity event severer than grade 2 was recorded. CONCLUSION: 3-weekly TH regimen has satisfactory pCR rate and OR rate in Chinese patients with Her-2 overexpressing operable breast cancer and reliable safety. PMID- 21029702 TI - [Curative effect of stereotactic 186Re endocavitary irradiation on cystic craniopharyngioma]. AB - OBJECTIVE: To evaluate the treatment results of stereotactic (186)Re intracavitary irradiation in the patients with craniopharyngioma. METHODS: Nineteen patients were treated with stereotactic (186)Re intracavitary irradiation, including 12 males and 7 females (average age, 37.2 years). Among them 12 patients had a solitary cyst, whereas 7 patients with mixed structure (e.g., a large cyst with a small solid portion). The mean volume of the cystic portion of the tumor before irradiation was 8390 mm(3). RESULTS: The patients were followed up for 6 months to 3 years. The retraction of the cyst was complete in 7 patients, cyst volume decreased more than 50% in 5 patients and less than 50% in 7 cases. Among the 8 patients with visual acuity deficit before irradiation, 5 were improved. No hypopituitarism occurred in patients with normal pituitary function before treatment. One of the 4 patients with hypopituitarism was improved, 3 of the 5 patients with diabetes insipidus was improved. CONCLUSION: Stereotactic (186)Re endocavitary irradiation for the treatment of cystic craniopharyngioma is a safe and effective procedure. PMID- 21029703 TI - [Comparison of preoperative T staging by oral contrast enhanced ultrasonography and double contrast enhanced ultrasonography in advanced gastric carcinoma]. AB - OBJECTIVE: To compare the accuracy of preoperative T staging of gastric cancer by oral and intravenous contrast-enhanced gastric ultrasonography. METHODS: One hundred and forty three patients who had been diagnosed as gastric cancer by endoscopic biopsy and confirmed by pathology after operation were examined by oral and intravenous contrast-enhanced gastric ultrasonography, and they were divided into satisfied group and non-satisfied group according to the 2-D image quality of lesion. The results were compared with postoperative pathologic findings. RESULTS: All the patients with gastric cancer presented regional gastric wall thickening. Among them, 117 cases were clearly presented with good image quality. The remaining 26 cases were presented with vague profile, the ulcerative surface of lesion was filled with hyperechogenicity combined with rear shadow. The accuracy of oral contrast-enhanced ultrasonography in determining the T stage of gastric cancer was 74.1%. The accuracy in satisfied group and non satisfied group was 78.6% and 53.8%, respectively. The enhancement pattern of 143 cases was showed as hyperenhancement during the arterial phase and hypoenhancement during the portal phase in DCUS. The accuracy of double contrast enhanced ultrasongraphy in determining the T stage of gastric cancer was 86.7%, but the accuracy in satisfied group and non-satisfied group was 88.9% and 76.9%, respectively. There was a significant difference between the two methods (chi(2) = 9.031, P < 0.01). CONCLUSION: DCUS is more accurate than oral contrast-enhanced ultrasonography as a useful diagnostic method for preoperative T staging of gastric cancer. PMID- 21029704 TI - [Practice and consideration on neoadjuvant therapy for early breast cancer]. PMID- 21029705 TI - [The origin and development of fragrance activity in Chinese ancient times]. AB - It has a long history of the fragrance activities in the ancient China. During the period of pre-Qin, it was mainly used in the therapy and worship. Until the Three Kingdoms, the crowd using the fragrance expanded from the royal to the literati and the general officials. People applied the spices to incense clothes, purify rooms, prevent and treat epidemic diseases in daily. In the worship, the spices were dedicated to Gods and other fairies. The fragrance was developed quickly during the period from Wei Dynasty to South and North Dynasties. People had more experiences of spices used as medicines, the formula of spices were used more widely. Then, during the period from Sui Dynasty to Song Dynasty, the fragrance activities climbed to the peak. The fragrance activities were institutionalized, when nobility matched their spices each other. The Literati made spice products and enjoyed the fragrance activities. Doctors knew more than before in the application experiences and species of spices. In the times of Yuan, Ming and Qing Dynasty, the fragrance activities spread among the public. The spices appeared in each side of the daily life of nobility, when natural fruits appeared in the fragrance activities. External therapy with spices appeared in the clinical. In addition to prevention and therapy, spices should be used in the embalming. After a long period, the fragrance activities had gradually developed into a kind of culture. PMID- 21029706 TI - [The meaning of "nue" and "gu" in the Five Classical Canons and Huangdi Neijing (Yellow Emperor's Inner Canon)]. AB - There were many terms of traditional Chinese medicine (TCM) in the Confucian Five Classical Canons, such as nue and gu. Among them, nue had the meaning of "sudden disease" or "cold disease" in the Spring and Autumn Period, which were changed to a name of disease, nue disease in the Warring States Period. In the Huangdi Neijing (Yellow Emperor's Inner Canon), there was a special treatise to discuss it. The original meaning of gu was poisonous insect, and then was explicated to a insect causing harm to people. Therefore, gu had the meaning of gathering gu for harming people, gu disease, gu poison and bug in the abdomen. Gu was recorded as a divinatory symbols in the Zhou Yi (The Book of Change), explained as a disease of heart-spirit confusion by later generations. Also, it was recorded in the Zuo Zhuan (The Commentary of Zuo Qiuming) and Huangdi Neijing. PMID- 21029707 TI - [Discussion of Tian Nian of Ling Shu (miraculous pivot)]. AB - During one's lifetime, the state of health and the life span in different people are different, also, our body has it's own specific physical situation at certain age, Tian Nian of Ling Shu (Miraculous Pivot) includes all of those content. To investigate this chapter may help our realization and practice of TCM physiology. PMID- 21029708 TI - [The prevention measures of plague in Hebei from 1946 to 1948]. AB - The plague was seriously occurred in Hebei from 1946 to 1948, which had a great impact on the local social economy and people's life. The public health system was established by the government, and people were instructed about the knowledge of health consciousness and life habits for controlling effectively the plague. The measures of giving medicine freely and social assistance were taken for preventing the plague in the folk. Thus, the plague was controlled in a short time. However, the effect of prevention was limited by the objective conditions. The color of western medicine was showed from these measures, and the "modernity" of the system at that time was indicated. PMID- 21029709 TI - [Analysis on the background of arising of Evidence-based medicine]. AB - Science is coming from the background of social culture. Evidence-based medicine (EBM) was generated at the early 90's of 20th Century, and there were some landmark things before its appearance. The background of EBM included: (1) risk control of medical techniques at the 70s of 20th Century; (2) ethical ideas of Protestant, including secularism, rationalism and utilitarianism; (3) British positivism and its tradition. PMID- 21029710 TI - [Research on interpretation, collation and annotation of a Heishui City document, Shen xian fang lun (On the Prescriptions of Immortals) preserved in Russia]. AB - Through interpretation, collation and annotation of Shen xian fang lun (On the Prescriptions of Immortals), Xixia document A21-1, found in Heishui City and now preserved in Russia, including the explanation of homonyms and mispronounced words, and comparison and analysis with other relevant literature, 12 prescriptions were found their original sources from Tai ping sheng hui fang (Taiping Holy Prescriptions for Universal Relief; Peaceful Holy Benevolent Prescriptions) and Sheng ji zong lu (General Records of Holy Universal Relief; Complete Record of Sacred Benevolence) etc. While a few others, never seen in ancient medical books, could be created of Xixia medical researchers based on local situation. PMID- 21029711 TI - [Research on Zhang's collated edition of Lei gong pao zhi lun (Master Lei's Discourse on Processing of Chinese Materia Medica)]. AB - Lei gong pao zhi lun (Master Lei's Discourse on Processing of Chinese Materia Medica) collated by Zhang Ji, and printed by Zhang's Yisheng Tang in Chengdu in 1932 was the first collated edition. Its original edition was not Jing shi zheng lei bei ji ben cao (Classified Materia Medica from Historical Classics for Emergency) of the Song Dynasty, but was Xiu shi zhi nan (Instruction for Drug Processing) and Lei gong pao zhi yao xing jie (Explanation on Master Lei's Properties of Drugs Processing) of the Qing Dynasty. The contents of this collated edition was far from Lei gong pao zhi lun with many mistakes, and was not the best edition to study Lei gong pao zhi lun. PMID- 21029712 TI - [Overview on branch hospital of Central Medical Hospital and the county hospitals in Guangdong province during the Republic of China]. AB - Central Medical Hospital were established in 1929. And then, based on the "Memorandum of Organization of Central Medical Hospital, Provincial and Municipal Branch", branch hospitals were set up in all provinces. Guangdong Branch and the county hospitals were established in 1931, and a variety of activities were carried out. However, because of the failure of striving for administrative power by Central Medical Hospital, the local Branch hospitals were defined as association. In addition, lack of powerful leaders and support of government led to the weakening of its function. They failed to develop traditional Chinese medicine further. PMID- 21029714 TI - [Brief history of percutaneous coronary intervention]. AB - Percutaneous coronary intervention (PCI) is that delivering balloon catheter and/or equipment such as a stent to the target coronary artery bypass peripheral artery, at the same time, expanding and opening the stenosis of coronary artery. Through several decades of development, PCI has become a most effective way to rescue patients with coronary heart disease and become one of the biggest advances in the field of heart disease. Because of the development of PCI, more lives have been saved in patients with coronary heart disease. However, PCI does not meet the point of perfection, still has a lot of issues remain to be further resolved. Through a review the development of PCI, we may be able to get some insights to perfect the treatment technique for the patients of coronary heart disease. PMID- 21029715 TI - [Brief explanation of shi lin (urolithic stranguria)]. AB - Shi lin (urolithic stranguria) is a kind of stranguria, manifested as pain occurred when pissing and sand-like in the urine, developed from the early concept of shi long. This name of disease was appeared firstly in Shen nong ben cao jing (Shennong's Classic of Materia Medica), and then, the disease name of sha lin, sha shi lin and sha lin were derived from it by the Song Dynasty. It was said that the disease with sha (sand-like) was easy to treat, and with shi (stone like) was difficult to cure. This disease was also happened in the children, and the reasons were the same with ones of the adult. Furthermore, there was a name of disease, xue sha lin, which was a kind of woman disease and had nothing to do with shi lin. PMID- 21029716 TI - [Textual research on Capital's Puji Tang (Relief Houses) in the Qing Dynasty]. AB - Puji Tang (Relief Houses) was established in 1706 with the function of helping the poor, comforting and compensating people by medicine, therefore, which was supported by the Emperors of the Qing Dynasty. As a representation of medical relief organization of the Qing Dynasty, Puji Tang was developed from a folk relief organization to a government national organization. Because of the declination of the Qing Empire and the problems within its own organization, Puji Tang changed finally to an organization of reeducation through labor in 1907. PMID- 21029717 TI - Intensity-modulated radiotherapy for the treatment of prostate cancer: a systematic review and economic evaluation. AB - BACKGROUND: Prostate cancer (PC) is the most common cancer in men in the UK. Radiotherapy (RT) is a recognised treatment for PC and high-dose conformal radiotherapy (CRT) is the recommended standard of care for localised or locally advanced tumours. Intensity-modulated radiotherapy (IMRT) allows better dose distributions in RT. OBJECTIVE: This report evaluates the clinical effectiveness and cost-effectiveness of IMRT for the radical treatment of PC. DATA SOURCES: The following databases were searched: MEDLINE (1950-present), EMBASE (1980-present), Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982-present), BIOSIS (1985-present), the Cochrane Database of Systematic Reviews (1991 present), the Cochrane Controlled Trials Register (1991-present), the Science Citation Index (1900-present) and the NHS Centre for Reviews and Dissemination databases (Database of Abstracts of Reviews of Effects, NHS Economic Evaluation Database, Health Technology Assessment) (1991-present). MEDLINE In-Process & Other Non-Indexed Citations was searched to identify any studies not yet indexed on MEDLINE. Current research was identified through searching the UK Clinical Research Network, National Research Register archive, the Current Controlled Trials register and the Medical Research Council Clinical Trials Register. In addition, abstracts of the American Society of Clinical Oncology, the American Society for Therapeutic Radiology and Oncology, and European Society for Therapeutic Radiology and Oncology conferences were browsed. REVIEW METHODS: A systematic literature review of the clinical effectiveness and cost-effectiveness of IMRT in PC was conducted. Comparators were three-dimensional conformal radiotherapy (3DCRT) or radical prostatectomy. Outcomes sought were overall survival, biochemical [prostate-specific antigen (PSA)] relapse-free survival, toxicity and health-related quality of life (HRQoL). Fifteen electronic bibliographic databases were searched in January 2009 and updated in May 2009, and the reference lists of relevant articles were checked. Studies only published in languages other than English were excluded. An economic model was developed to examine the cost-effectiveness of IMRT in comparison to 3DCRT. Four scenarios were modelled based on the studies which reported both PSA survival and late gastrointestinal (GI) toxicity. In two scenarios equal PSA survival was assumed for IMRT and 3DCRT, the other two having greater PSA survival for the IMRT cohort. As there was very limited data on clinical outcomes, the model estimates progression to clinical failure and PC death from the surrogate outcome of PSA failure. RESULTS: No randomised controlled trials (RCTs) of IMRT versus 3DCRT in PC were available, but 13 non-randomised studies comparing IMRT with 3DCRT were found, of which five were available only as abstracts. One abstract reported overall survival. Biochemical relapse-free survival was not affected by treatment group, except where there was a dose difference between groups, in which case higher dose IMRT was favoured over lower dose 3DCRT. Most studies reported an advantage for IMRT in GI toxicity, attributed to increased conformality of treatment compared with 3DCRT, particularly with regard to volume of rectum treated. There was some indication that genitourinary toxicity was worse for patients treated with dose escalated IMRT, although most studies did not find a significant treatment effect. HRQoL improved for both treatment groups following radiotherapy, with any group difference resolved by 6 months after treatment. No comparative studies of IMRT versus prostatectomy were identified. No comparative studies of IMRT in PC patients with bone metastasis were identified. LIMITATIONS: The strength of the conclusions of this review are limited by the lack of RCTs, and any comparative studies for some patient groups. CONCLUSIONS: The comparative data of IMRT versus 3DCRT seem to support the theory that higher doses, up to 81 Gy, can improve biochemical survival for patients with localised PC, concurring with data on CRT. The data also suggest that toxicity can be reduced by increasing conformality of treatment, particularly with regard to GI toxicity, which can be more easily achieved with IMRT than 3DCRT. Whether differences in GI toxicity between IMRT and 3DCRT are sufficient for IMRT to be cost-effective is uncertain, depending on the difference in incidence of GI toxicity, its duration and the cost difference between IMRT and 3DCRT. PMID- 21029718 TI - Investigations into the isolation of the Tukuyu focus of onchocerciasis (Tanzania) from S. damnosum s.l. vector re-invasion. AB - As part of the feasibility study for an onchocerciasis vector elimination project we investigated the isolation of the Tukuyu focus in Tanzania from possible vector re-invasion. This was achieved by examining the distribution of the Simulium damnosum complex vector cytospecies outside the focus to look for potential sources of re-invasion. Besides cytotaxonomic identifications of the aquatic stages, we applied morphotaxonomic and molecular techniques to identify S. thyolense and confirm it as the anthropophilic species in both the Tukuyu and the neighbouring Ruvuma foci. We detected significant differences in chromosome inversion frequencies between the Tukuyu populations and those breeding to the southwest in the adjacent Songwe river basin and in northern Malawi (where there is no man-biting and no onchocerciasis), suggesting that there is not normally a great deal of migration in either direction. By contrast, populations of S. thyolense from the Tukuyu and Ruvuma foci (150km southeast of Tukuyu) were much more similar in terms of their chromosomal polymorphisms, indicating a higher possibility of re-invasion, although migration is still restricted to some extent, as indicated by some differences in chromosome polymorphisms between the two foci. Future migratory events which might be associated with vector control operations can be monitored by vector cytospecies identification, the frequency of polymorphic inversions which characterise the different vector populations, and the identification of accompanying non-vector cytospecies (e.g. S. plumbeum and cytotype Kasyabone occur exclusively in the two foci, and hence their re appearance in Tukuyu could have only one outside source). The morphology of the scutal pattern of neonate males may act as a quick test for vector species identification where chromosome squashes are unavailable. PMID- 21029719 TI - Akt/Nox2/NF-kappaB signaling pathway is involved in Tat-induced HIV-1 long terminal repeat (LTR) transactivation. AB - Human immunodeficiency virus (HIV) regulatory protein Tat has pro-oxidant property, which might contribute to Tat-induced long terminal repeat region (LTR) transactivation. However, the intracellular mechanisms whereby Tat triggers ROS production, and the relationship between Tat-induced ROS production and LTR transactivation, are still subject to debate. The present study was undertaken to evaluate the specific effects of Tat on nicotinamide adenine denucleotide phosphate (NADPH) oxidase in MAGI cells, and to determine the specific role of NADPH oxidase in Tat-induced LTR transactivation. Application of Tat to MAGI cells caused increases in ROS formation that were prevented by both pharmacologic NADPH oxidase inhibitors and by siRNA Nox2, but not by other inhibitors of pro oxidant enzymes or siRNA Nox4. Furthermore, inhibition of NADPH oxidase by both pharmacologic NADPH oxidase inhibitors and by siRNA Nox2 attenuated Tat-induced p65 phosphorylation and IKK phosphorylation. Phosphatidylinositol 3-kinase/Akt signaling pathway was involved in Tat-induced NADPH oxidase stimulation. Finally, NADPH oxidase inhibitors or Nox2 siRNA, but not control siRNA, inhibited Tat induced LTR transactivation. Tat-induced HIV-1 LTR transactivation was inhibited in wortmannin or LY294002 treated cells compared to control cells. Together, these data describe a specific and biologically significant signaling component of the MAGI cells response to Tat, and suggest the PI3K/Akt signaling pathway might originate in part with Tat-induced activation of NADPH oxidase and LTR transactivation. PMID- 21029720 TI - Structure and biogenesis of the chloroplast NAD(P)H dehydrogenase complex. AB - Eleven genes (ndhA-ndhK) encoding proteins homologous to the subunits of bacterial and mitochondrial NADH dehydrogenase (complex I) were found in the plastid genome of most land plants. These genes encode subunits of the chloroplast NAD(P)H dehydrogenase (NDH) complex involved in photosystem I (PSI) cyclic electron transport and chlororespiration. Although the chloroplast NDH is believed to be closely and functionally related to the cyanobacterial NDH-1L complex, extensive proteomic, genetic and bioinformatic studies have discovered many novel subunits that are specific to higher plants. On the basis of extensive mutant characterization, the chloroplast NDH complex is divided into four parts, the A, B, membrane and lumen subcomplexes, of which subunits in the B and lumen subcomplexes are specific to higher plants. These results suggest that the structure of NDH has been drastically altered during the evolution of land plants. Furthermore, chloroplast NDH interacts with multiple copies of PSI to form the unique NDH-PSI supercomplex. Two minor light-harvesting-complex I (LHCI) proteins, Lhca5 and Lhca6, are required for the specific interaction between NDH and PSI. The evolution of chloroplast NDH in land plants may be required for development of the function of NDH to alleviate oxidative stress in chloroplasts. In this review, we summarize recent progress on the subunit composition and structure of the chloroplast NDH complex, as well as the information on some factors involved in its assembly. This article is part of a Special Issue entitled: Regulation of Electron Transport in Chloroplasts. PMID- 21029721 TI - The structural basis of secondary active transport mechanisms. AB - Secondary active transporters couple the free energy of the electrochemical potential of one solute to the transmembrane movement of another. As a basic mechanistic explanation for their transport function the model of alternating access was put forward more than 40 years ago, and has been supported by numerous kinetic, biochemical and biophysical studies. According to this model, the transporter exposes its substrate binding site(s) to one side of the membrane or the other during transport catalysis, requiring a substantial conformational change of the carrier protein. In the light of recent structural data for a number of secondary transport proteins, we analyze the model of alternating access in more detail, and correlate it with specific structural and chemical properties of the transporters, such as their assignment to different functional states in the catalytic cycle of the respective transporter, the definition of substrate binding sites, the type of movement of the central part of the carrier harboring the substrate binding site, as well as the impact of symmetry on fold specific conformational changes. Besides mediating the transmembrane movement of solutes, the mechanism of secondary carriers inherently involves a mechanistic coupling of substrate flux to the electrochemical potential of co-substrate ions or solutes. Mainly because of limitations in resolution of available transporter structures, this important aspect of secondary transport cannot yet be substantiated by structural data to the same extent as the conformational change aspect. We summarize the concepts of coupling in secondary transport and discuss them in the context of the available evidence for ion binding to specific sites and the impact of the ions on the conformational state of the carrier protein, which together lead to mechanistic models for coupling. PMID- 21029722 TI - IgG-mediated systemic anaphylaxis to protein antigen can be induced even under conditions of limited amounts of antibody and antigen. AB - Systemic anaphylaxis is an acute, severe, and potentially fatal allergic reaction. Two classes of antibodies, IgE and IgG, contribute to the development of anaphylaxis in mice, through different mechanisms with distinct usage of effector cells and chemical mediators. Larger quantities of antibody and antigen are reportedly required to induce IgG-mediated anaphylaxis than IgE-mediated one, suggesting that the former may not happen as frequently as the latter in real life. To readdress this issue, we established in the present study a novel mouse model of passive IgG-mediated systemic anaphylaxis to a native protein antigen, ovalbumin (OVA), rather than artificially haptenated protein antigens used in previous studies. Passive sensitization of mice with a cocktail of but not individual IgG1 mAbs specific to distinct OVA epitopes elicited systemic anaphylaxis in response to OVA challenge. Importantly, much smaller doses of antibody and antigen than previously reported were sufficient for the induction of IgG-mediated systemic anaphylaxis. Moreover, a relatively small dose of antigen could induce severe anaphylaxis through both IgE- and IgG-mediated mechanisms when mice had been passively sensitized with antigen-specific IgE and IgG. These results strongly suggest that IgG-mediated systemic anaphylaxis is not rare among antibody-mediated systemic anaphylaxis, in contrast to previous thought, and significantly contributes to active systemic anaphylaxis in real life, at least in mice. PMID- 21029723 TI - dGIPC is required for the locomotive activity and longevity in Drosophila. AB - To identify genes that function in the adult neural system, we screened pools of P element-mediated mutants and tested locomotor activity of homozygous flies. Of 1014 P element-mutagenized lines, 638 were homozygous viable. These lines were tested for climbing ability and lifespan. We isolated dGIPC, a Drosophila homolog of GIPC, that produced a 50% premature loss of locomotor activity and a 30% reduction in life span. We found that dGIPC is expressed in the central brain of adult flies, especially in glia and dopaminergic (DA) neurons. Inhibition of dGIPC expression in DA neurons significantly affected climbing ability and survival. In vertebrates, interactions between GIPC with dopamine receptors have been reported. Our findings, together with those obtained from vertebrate models, suggest that DrosophiladGIPC acts in the adult central nervous system and may be required to regulate the trafficking of dopamine receptors needed for proper functioning of dopaminergic neurons. PMID- 21029724 TI - RAG-dependent recombination at cryptic RSSs within TEL-AML1 t(12;21)(p13;q22) chromosomal translocation region. AB - The recombination activating gene (RAG) is a lymphoid-specific endonuclease involved in the V(D)J recombination. It has long been proposed that mis-targeting of RAG proteins is one of the factors contributing to lymphoid chromosomal translocation bearing authentic recombination signal sequences (RSSs) in immunoglobulin (Ig) and T cell receptor (TCR) gene loci or cryptic RSSs (cRSSs). However, it is unclear whether primary sequence-dependent targeting mistake involved in the chromosomal translocation bearing no Ig/TCR gene loci is mediated by RAG proteins. Using an extrachromosomal recombination assay, we found RAG dependent recombination in the regions dense in breakpoints within TEL and AML1 gene loci related to acute lymphoid leukemia-associated t(12;21)(p13;q22) chromosomal translocation. Sequence analyses revealed several heptamer-like sequences located in the vicinity of RAG-dependent recombination sites. By chromatin immunoprecipitation (ChIP) and ligation-mediated PCR (LM-PCR) assays, we have shown that RAG proteins bind to and cleave the TEL translocation region dense in breakpoints. These results suggest that mis-targeting of RAG proteins to cRSSs within TEL and AML1 translocation regions might be responsible for the t(12;21)(p13;q22) chromosomal translocation not bearing Ig/TCR regions. PMID- 21029725 TI - The NMR solution structure of human epidermal growth factor (hEGF) at physiological pH and its interactions with suramin. AB - Human epidermal growth factor (hEGF) induces the proliferation, differentiation and survival of various cell types including tumor-derived cells. Generally, hEGF performs its biological function by binding to a specific receptor (hEGFR) on the cell surface, thereby inducing signal transduction. Suramin, a polysulfonated naphthylurea that acts as a growth factor blocker, exhibits antiproliferative activity against non-small cell lung cancer (NSCLC) cells that overexpress EGFR on the cell surface. We determined the solution structure of hEGF under physiological conditions and investigated the interaction of suramin with hEGF using isothermal titration calorimetry and NMR spectroscopy techniques. The solution structure of hEGF presented in this paper is different from the bound form of hEGF present in the crystal structure of the 2:2 EGF-EGFR complex because its C-tail contains a hydrophobic core. This conformational difference supports the hypothesis that hEGF undergoes a conformational change when it binds to hEGFR and subsequently induces signal transduction. Based on the docking structure of the hEGF-suramin complex, we demonstrated how suramin blocks hEGF by binding to its receptor binding site (the C-terminal region around Arg45) and inhibits the crucial conformational change. PMID- 21029726 TI - Is animacy special? ERP correlates of semantic violations and animacy violations in sentence processing. AB - Animacy is often conceived as a special semantic feature because of its relevance to thematic and syntactic processing. This study uses event-related brain potentials to investigate whether violations of the expected animacy value of a noun are processed differently from semantic violations which preserve the expected animacy value in a situation in which the animate/inanimate distinction has no consequences for thematic or syntactic processing. The language under test is Polish, a language in which the animate-inanimate distinction is reflected in the inflection of nouns. We constructed short stories such that either an animate direct object noun is highly expected in the story's final sentence, or an inanimate direct object. This noun appears in one of three conditions: (a) congruent, i.e. fitting the preceding context, (b) semantic violation without a violation of the expected animacy value, or (c) animacy violation, i.e. a violation of the expected animacy value. Semantic violations and animacy violations elicited a biphasic N400/P600 pattern. The N400 effect had the same amplitude for the two types of violation, while the P600 elicited by animacy violations had a significantly higher amplitude than the P600 elicited by semantic violations. These results indicate that animacy is processed differently from other semantic features even in syntactically and thematically unambiguous positions in a sentence. PMID- 21029727 TI - Subcellular compartmentalization of proteolytic enzymes in brain regions and the effects of chronic beta-amyloid treatment. AB - Amyloid beta-protein (Abeta) is the major amyloid component of toxic amyloid senile plaques inducing slow neuronal degeneration in brains of Alzheimer's patients. It can induce proteolysis of some cytoskeletal proteins in the neuron; however, studies of proteolytic enzyme activity in different brain regions and their subcellular compartmentalization were not carried out. In this work, the effects of chronic intracerebroventricular administration of Abeta(25-35) on proteolytic enzymes in subcellular fractions from rat brain regions were studied. Mitochondrial and cytosolic caspase-9 and caspase-3 activities in neocortex, cerebellum, and hippocampus were shown to be increased during infusion of Abeta(25-35). In Abeta(25-35)-treated rats, cytosolic calcium-dependent thiol proteases calpain-1 and calpain-2 appeared in mitochondria and lysosomes, causing apparent release of lysosomal cathepsins B and D to mitochondria and of beta galactosidase to the cytosol. The increase in all proteolytic activities in brain subcellular fractions under the influence of administered Abeta suggests that these enzymes could be transferred across intracellular membranes and involved in neurodegeneration. PMID- 21029728 TI - Defining the cognitive phenotype of autism. AB - Although much progress has been made in determining the cognitive profile of strengths and weaknesses that characterise individuals with autism spectrum disorders (ASDs), there remain a number of outstanding questions. These include how universal strengths and deficits are; whether cognitive subgroups exist; and how cognition is associated with core autistic behaviours, as well as associated psychopathology. Several methodological factors have contributed to these limitations in our knowledge, including: small sample sizes, a focus on single domains of cognition, and an absence of comprehensive behavioural phenotypic information. To attempt to overcome some of these limitations, we assessed a wide range of cognitive domains in a large sample (N=100) of 14- to 16-year-old adolescents with ASDs who had been rigorously behaviourally characterised. In this review, we will use examples of some initial findings in the domains of perceptual processing, emotion processing and memory, both to outline different approaches we have taken to data analysis and to highlight the considerable challenges to better defining the cognitive phenotype(s) of ASDs. Enhanced knowledge of the cognitive phenotype may contribute to our understanding of the complex links between genes, brain and behaviour, as well as inform approaches to remediation. PMID- 21029729 TI - MMN evidence for asymmetry in detection of IOI shortening and lengthening at behavioral indifference tempo. AB - Most behavioral investigations indicated an indifference interval of 500-700 ms, at which the detection of inter-onset interval (IOI) shortening and lengthening are equally difficult and no perceptual bias would be expected. However, some event-related potential (ERPs) studies showed that even at this behavioral indifference time, the detection of shortening and lengthening might rely on different aspects of information processing. This work was aimed to investigate whether the pre-attentive processing of local tempo perturbations, i.e., IOI shortening and lengthening, are different when the basic tempo is at the behavioral indifference area. Tempo perturbations were introduced by shortening or lengthening the third IOI by 10% of the base IOI of the 5-beat isochronous sequence. ERPs recorded in a passive experiment showed that both tempo perturbations elicited a distinct frontal mismatch negativity (MMN). The low resolution electromagnetic tomography (LORETA) source estimation indicated a left prefrontal predominance activity around the MMN peak, implicating an important role of the frontal lobe in the processing of local tempo perturbations. Statistical analysis revealed that the MMN to IOI shortening had an earlier and greater peak than that to IOI lengthening, implying that IOI shortening might be more easily to be detected than IOI lengthening even at indifference tempo. Our results suggested that local IOI perturbations at behavioral indifference area have an asymmetric effect on the pre-attentive processing of temporal variation detection. PMID- 21029730 TI - Decrease in dystrophin expression prior to disruption of brain-blood barrier within the rat piriform cortex following status epilepticus. AB - Increased permeability of the brain-blood barrier (BBB) in the piriform cortex (PC) has been reported in various animal models of temporal lobe epilepsy. Since BBB disruption induced by epileptogenic insult has not fully clarified, we attempted to determine whether changes in BBB-related molecules are associated with vasogenic edema in the PC. One day after status epilepticus (SE), PC neurons and astrocytes showed a pyknotic nucleus and shrunken cytoplasm accompanied by vasogenic edema. At this time point, SMI-71 (an endothelial barrier antigen) immunoreactivity had decreased in the PC. Prior to vasogenic edema formation (12 h after SE), dystrophin immunoreactivity disappeared within astrocytes, while the change in glial fibrillary acidic protein immunoreactivity was negligible. However, glucose transporter-1 (an endothelial cell marker) had increased at 12 h after SE. These findings indicate that dysfunction of dystrophin induced by SE may result in endothelial and astroglial damage with BBB breakdown and increase vascular permeability, leading to vasogenic edema that is involved in pathogenesis of epileptogenesis. PMID- 21029731 TI - A novel function for KIF13B in germ cell migration. AB - Primordial germ cell (PGC) development in Xenopus embryos relies on localised maternal determinants. We report on the identification and functional characterisation of such one novel activity, a germ plasm associated mRNA encoding for the Xenopus version of a kinesin termed KIF13B. Modulations of xKIF13B function result in germ cell mismigration and in reduced numbers of such cells. PGCs explanted from Xenopus embryos form bleb-like protrusions enriched in PIP3. Knockdown of xKIF13B results in inhibition of blebbing and PIP3 accumulation. Interference with PIP3 synthesis leads to PGC mismigration in vivo and in vitro. We propose that xKIF13B function is linked to polarized accumulation of PIP3 and directional migration of the PGCs in Xenopus embryos. PMID- 21029732 TI - Regulation of Cyr61/CCN1 expression by hypoxia through cooperation of c-Jun/AP-1 and HIF-1alpha in retinal vascular endothelial cells. AB - Hypoxia is the most important factor in the pathogenesis of diabetic retinopathy. Cysteine-rich 61 (Cyr61) is one of the angiogenic factors involved in the development of proliferative diabetic retinopathy (PDR). The aim of this study was to investigate the mechanism of hypoxia-induced Cyr61 expression in retinal vascular endothelial cells. The hypoxia-induced expression of mRNA and protein of Cyr61 was studied in monkey choroidal retinal vascular endothelial (RF/6A) cells. Luciferase reporter assays and electrophoretic mobility shift assays were used to identify the hypoxia responsible region and transcription factors in the Cyr61 promoter. Chromatin immunoprecipitation and immunoprecipitation were performed to study the role of hypoxia-inducible factor (HIF)-1alpha and c-Jun/activator protein-1 (AP-1) in Cyr61 transcriptional regulation. The results showed that hypoxia significantly induced Cyr61 mRNA and protein expression in RF/6A cells. The effect was mediated through phosphorylation of c-Jun. Luciferase assays, electrophoretic mobility shift assays, chromatin immunoprecipitation and immunoprecipitation showed that HIF-1alpha interacted with c-Jun/AP-1 and their binding on the AP-1 binding motif within the Cyr61 promoter induced the expression of Cyr61. In conclusion, hypoxia controlled the transcriptional regulation of the Cyr61 gene in RF/6A cells by cooperation of HIF-1alpha and c Jun/AP-1. Cyr61 might play an important role in ischemic retinal diseases, such as PDR. PMID- 21029733 TI - Differential roles of AMPKalpha1 and AMPKalpha2 in regulating 4-HNE-induced RPE cell death and permeability. AB - Lipid peroxidation products such as 4-hydroxy-2-nonenal (4-HNE) cause dysfunction and death of retinal pigmented epithelial (RPE) cells, thereby leading to retinal degeneration. The molecular mechanisms underlying their action remain elusive however. In this study, the roles of AMP-activated protein kinase (AMPK) in 4-HNE induced RPE cell dysfunction and viability were addressed. 4-HNE caused RPE cell death and down-regulated basal activity of AMPK as evidenced by decreased Thr(172) phosphorylation of AMPKalpha. Exposure of RPE cells to the AMPK inhibitor, compound C also led to cell death, indicating that RPE cell death is correlated with 4-HNE modulation of AMPK activity. ARPE19 cells express both AMPKalpha1 and AMPKalpha2 with predominant expression of the AMPKalpha1 isoform. siRNA studies revealed that knockdown of AMPKalpha1 expression sensitized RPE cells to 4-HNE. Intriguingly, knockdown of AMPKalpha2 protected RPE cells from 4 HNE injury. Sub-lethal doses of 4-HNE induced an increase in RPE monolayer permeability, as measured by reduction in trans-epithelial resistance (TER). Knockdown of AMPKalpha2 but not AMPKalpha1 significantly restored RPE cell barrier function. No further protection was observed by knockdown of both AMPKalpha1 and AMPKalpha2. In contrast, knockdown of AMPKalpha1 and/or AMPKalpha2 did not reverse the 4-HNE's inhibitory effects on production of IL-8 and MCP-1. These data demonstrate that AMPKalpha1 and AMPKalpha2 play distinct roles in regulating 4-HNE effects on RPE function and viability. Therefore, selective modulation of AMPKalpha activity may benefit patients with retinal degeneration associated with RPE cell atrophy. PMID- 21029735 TI - Effects of egg testosterone on female mate choice and male sexual behavior in the pheasant. AB - Evidence is accumulating that sex steroids in the eggs, besides affecting progeny phenotype and behavior in the short term, also have enduring effects until adulthood, when they may translate into differences in reproductive strategies and success. Maternal steroids transfer may therefore affect both agonistic behavior and mate choice decisions, either through the promotion of body size and condition or through a priming effect on the neuroendocrine system. However, owing to the prevalence of a short-term perspective, relevance of maternal transfer of sex steroids to sexual selection processes has been seldom studied. Here we investigate the effects of an experimental increase in egg testosterone on male dominance and copulation success in the ring-necked pheasant, Phasianus colchicus, a polygynous galliform with multiple male ornamental traits, in captivity. We found that females from testosterone (T) injected eggs copulated less than control females. Males from T-injected eggs obtained more copulations than control males, specifically with control females. The effect of male 'ordinary' and secondary sexual traits on either dominance or copulation frequency did not depend on early exposure to T, nor did T treatment affect male dominance. Present results demonstrate that variation in the early hormonal environment set up by mothers affects sexual behavior of the offspring, which might translate into fitness differences. PMID- 21029734 TI - The role of Bisphenol A in shaping the brain, epigenome and behavior. AB - Bisphenol A (BPA) is a xenoestrogen that was first synthesized in 1891. Its estrogenic properties were discovered in 1930, and shortly after that chemists identified its usefulness in the production of epoxy resins. Since the 1950s BPA has been used as a synthetic monomer in the manufacturing of polycarbonate plastic, polystyrene resins, and dental sealants. Roughly 6.5 billion pounds of BPA are produced each year and it is the major estrogenic compound that leaches into nearby water and food supplies (vom Saal et al., 2007). BPA has been detected in 95% of human urine samples, which indicates that environmental exposure is widespread (Calafat et al., 2005). Moreover, BPA affects reproductive tissues and the brain. Thus many studies have focused on the effects of BPA during embryonic development. The most recent FDA update (Administration January 2010) points to "some concern about the potential effects of Bisphenol A on the brain, behavior, and prostate gland in fetuses, infants, and young children." In light of this concern, we present an updated review of BPA's action on the brain and behavior. We begin with a discussion of BPA's role as both an endocrine active compound and an agent that alters DNA methylation. Next, we review publications that have reported effects of BPA on brain and behavior. We end with our interpretation of these data and suggestions for future research directions. PMID- 21029736 TI - Conditioned sexual arousal in a nonhuman primate. AB - Conditioning of sexual arousal has been demonstrated in several species from fish to humans but has not been demonstrated in nonhuman primates. Controversy exists over whether nonhuman primates produce pheromones that arouse sexual behavior. Although common marmosets copulate throughout the ovarian cycle and during pregnancy, males exhibit behavioral signs of arousal, demonstrate increased neural activation of anterior hypothalamus and medial preoptic area, and have an increase in serum testosterone after exposure to odors of novel ovulating females suggestive of a sexually arousing pheromone. Males also have increased androgens prior to their mate's ovulation. However, males presented with odors of ovulating females demonstrate activation of many other brain areas associated with motivation, memory, and decision making. In this study, we demonstrate that male marmosets can be conditioned to a novel, arbitrary odor (lemon) with observation of erections, and increased exploration of the location where they previously experienced a receptive female, and increased scratching in post-conditioning test without a female present. This conditioned response was demonstrated up to a week after the end of conditioning trials, a much longer lasting effect of conditioning than reported in studies of other species. These results further suggest that odors of ovulating females are not pheromones, strictly speaking and that marmoset males may learn specific characteristics of odors of females providing a possible basis for mate identification. PMID- 21029737 TI - Potential contribution of prenatal estrogens to the sexual differentiation of mate preferences in mice. AB - The neural mechanisms controlling sexual behavior are sexually differentiated by perinatal actions of gonadal hormones. We recently observed using female mice deficient in alpha-fetoprotein (AFP-KO) and which lack the protective actions of AFP against maternal estrogens, that exposure to prenatal estrogens completely defeminized their potential to show lordosis behavior in adulthood. Therefore, we determined here whether mate preferences were also affected in female AFP-KO mice. We observed a robust preference for an estrous female over an intact male in female AFP-KO mice, which were ovariectomized in adulthood and subsequently treated with estradiol and progesterone, whereas similarly treated WT females preferred the intact male over the estrous female. Gonadally intact WT males preferred the estrous female over the male, but only when visual cues were blocked by placing stimulus animals behind opaque partitions. Furthermore, when given the choice between an intact male and a castrated male, WT females preferred the intact male, whereas AFP-KO females showed no preference. Finally when given the choice between an estrous female and an ovariectomized female, WT males preferred the estrous female whereas AFP-KO females preferred the ovariectomized female or showed no preference depending on whether they could see the stimulus animals or not. Taken together, when AFP-KO females are tested under estrous conditions, they do not show any male-directed preferences, indicating a reduced sexual motivation to seek out the male in these females. However, they do not completely resemble males in their mate preferences suggesting that the male typical pattern of mate preferences is not solely organized by prenatal estrogens. PMID- 21029738 TI - Insect photoperiodic calendar and circadian clock: independence, cooperation, or unity? AB - The photoperiodic calendar is a seasonal time measurement system which allows insects to cope with annual cycles of environmental conditions. Seasonal timing of entry into diapause is the most often studied photoperiodic response of insects. Research on insect photoperiodism has an approximately 80-year-old tradition. Despite that long history, the physiological mechanisms underlying functionality of the photoperiodic calendar remain poorly understood. Thus far, a consensus has not been reached on the role of another time measurement system, the biological circadian clock, in the photoperiodic calendar. Are the two systems physically separated and functionally independent, or do they cooperate, or is it a single system with dual output? The relationship between calendar and clock functions are the focus of this review, with particular emphasis on the potential roles of circadian clock genes, and the circadian clock system as a whole, in the transduction pathway for photoperiodic token stimulus to the overt expression of facultative diapause. PMID- 21029739 TI - The next step in gene delivery: molecular engineering of adeno-associated virus serotypes. AB - Delivery is at the heart of gene therapy. Viral DNA delivery systems are asked to avoid the immune system, transduce specific target cell types while avoiding other cell types, infect dividing and non-dividing cells, insert their cargo within the host genome without mutagenesis or to remain episomal, and efficiently express transgenes for a substantial portion of a lifespan. These sought-after features cannot be associated with a single delivery system, or can they? The Adeno-associated virus family of gene delivery vehicles has proven to be highly malleable. Pseudotyping, using AAV serotype 2 terminal repeats to generate designer shells capable of transducing selected cell types, enables the packaging of common genomes into multiple serotypes virions to directly compare gene expression and tropism. In this review the ability to manipulate this virus will be examined from the inside out. The influence of host cell factors and organism biology including the immune response on the molecular fate of the viral genome will be discussed as well as differences in cellular trafficking patterns and uncoating properties that influence serotype transduction. Re-engineering the prototype vector AAV2 using epitope insertion, chemical modification, and molecular evolution not only demonstrated the flexibility of the best-studied serotype, but now also expanded the tool kit for molecular modification of all AAV serotypes. Current AAV research has changed its focus from examination of wild-type AAV biology to the feedback of host cell/organism on the design and development of a new generation of recombinant AAV delivery vehicles. This article is part of a Special Section entitled "Special Section: Cardiovascular Gene Therapy". PMID- 21029740 TI - Enhancing the contrast of ApoB to locate the surface components in the 3D density map of human LDL. AB - A 26 A resolution map of the structure of human low-density lipoprotein (LDL) was obtained from electron cryomicroscopy and single-particle image reconstruction. The structure showed a discoidal-shaped LDL particle with high-density regions mainly distributed at the edge of the particle and low-density regions at the flat surface that covers the core region. To determine the chemical components that correspond to these density regions and to delineate the distribution of protein and phospholipid located at the particle surface at the resolution of the map, we used Mono-Sulfo-NHS-Undecagold labeling to increase preferentially the contrast of the apolipoprotein B component on the LDL particle. In the three dimensional map from the image reconstruction of the undecagold-labeled LDL particles, the high-density region from the undecagold label was distributed mainly at the edge of the particle, and lower density regions were found at the flat surfaces that cover the neutral lipid core. This suggests that apolipoprotein B mainly encircles LDL at the edge of the particle and the phospholipid monolayers are located at the flat surfaces, which are parallel to the cholesterol ester layers in the core and may interact with the core lipid layers through the acyl chains. PMID- 21029742 TI - Effects of snout dimensions on the hydrodynamics of suction feeding in juvenile and adult seahorses. AB - Seahorses give birth to juveniles having a fully functional feeding apparatus, and juvenile feeding behaviour shows striking similarities to that of adults. However, a significant allometric growth of the snout is observed during which the snout shape changes from relatively short and broad in juveniles to relatively long and slender in adults. Since the shape of the buccal cavity is a critical determinant of the suction performance, this snout allometry will inevitably affect the suction feeding ability. To test whether the snout is optimised for suction feeding throughout an ontogeny, we simulated the expansion of different snout shapes varying from extremely long and slender to short and broad for juvenile and adult snout sizes, using computational fluid dynamic models. Our results showed that the snout diameter at the start of the simulations is involved in a trade-off between the realizable suction volume and expansion time on the one hand (improving with larger initial diameters), and maximal flow velocity on the other hand (improving with smaller initial diameters). Moreover suction performance (suction volume as well as maximal attainable flow velocity) increased with decreasing snout length. However, an increase in snout length decreases the time to reach the prey by the cranial rotation, which may explain the prevalence of long snouts among syngnathid fishes despite the reduced suction performance. Thus, the design of the seahorse snout revolves around a trade-off between the ability to generate high-volume suction versus minimisation of the time needed to reach the prey by the cranial rotation. PMID- 21029741 TI - Evolution of I-SceI homing endonucleases with increased DNA recognition site specificity. AB - Elucidating how homing endonucleases undergo changes in recognition site specificity will facilitate efforts to engineer proteins for gene therapy applications. I-SceI is a monomeric homing endonuclease that recognizes and cleaves within an 18-bp target. It tolerates limited degeneracy in its target sequence, including substitution of a C:G(+4) base pair for the wild-type A:T(+4) base pair. Libraries encoding randomized amino acids at I-SceI residue positions that contact or are proximal to A:T(+4) were used in conjunction with a bacterial one-hybrid system to select I-SceI derivatives that bind to recognition sites containing either the A:T(+4) or the C:G(+4) base pairs. As expected, isolates encoding wild-type residues at the randomized positions were selected using either target sequence. All I-SceI proteins isolated using the C:G(+4) recognition site included small side-chain substitutions at G100 and either contained (K86R/G100T, K86R/G100S and K86R/G100C) or lacked (G100A, G100T) a K86R substitution. Interestingly, the binding affinities of the selected variants for the wild-type A:T(+4) target are 4- to 11-fold lower than that of wild-type I SceI, whereas those for the C:G(+4) target are similar. The increased specificity of the mutant proteins is also evident in binding experiments in vivo. These differences in binding affinities account for the observed ~36-fold difference in target preference between the K86R/G100T and wild-type proteins in DNA cleavage assays. An X-ray crystal structure of the K86R/G100T mutant protein bound to a DNA duplex containing the C:G(+4) substitution suggests how sequence specificity of a homing enzyme can increase. This biochemical and structural analysis defines one pathway by which site specificity is augmented for a homing endonuclease. PMID- 21029743 TI - Effects of cannabinoid CB1 receptor agonism and antagonism on SKF81297-induced dyskinesia and haloperidol-induced dystonia in Cebus apella monkeys. AB - Antipsychotic drugs may cause extrapyramidal symptoms (EPS), such as dyskinesia and dystonia. These effects are believed to involve dysfunctional striatal dopamine transmission. Patients with schizophrenia show increased prevalence of cannabis abuse and this has been linked to severity of EPS. Endocannabinoids modulate striatal dopamine activity via type 1 cannabinoid (CB(1)) receptors, and studies in rats and humans suggest beneficial effects of CB(1) ligands on EPS. The present study explored the effects of CB(1) receptor ligands on oral dyskinesia induced by the dopamine D(1) receptor agonist SKF81297 (SKF) and acute dystonia induced by the dopamine D(2) receptor antagonist haloperidol in Cebus apella monkeys. The monkeys were sensitised to EPS by prior exposure to D(2) receptor antagonists. SKF (0.3 mg/kg) was administered alone and in combination with the CB(1) agonist CP55,940 (0.0025-0.01 mg/kg) or the CB(1) antagonist SR141716A (0.25-0.75 mg/kg). Haloperidol (individual doses at 0.01-0.02 mg/kg) was administered alone and in combination with CP55,940 (0.005 or 0.01 mg/kg) or SR141716A (0.5 or 0.75 mg/kg). Subsequently, the monkeys were videotaped, and the recordings were rated for oral dyskinesia or dystonia. SKF-induced oral dyskinesia was dose-dependently reduced by CP55,940, with no effect of SR141716A. Haloperidol-induced dystonia was not affected by either CP55,940 or SR141716A. PMID- 21029745 TI - Comparison of effects of botulinum toxin subtype A1 and A2 using twitch tension assay and rat grip strength test. AB - Botulinum toxin type A is used as a therapeutic agent for some spastic neurological disorders. Type A organisms have been classified into four subtypes (A1 to A4) based on the amino acid sequence variability of the produced neurotoxin. At present, commercially available preparations of the toxin belong to subtype A1. To date, no study has compared the characteristics of the biological activity of toxins from different subtypes. We compared the efficacy of A1 toxin (LL toxin or neurotoxin: NTX) with that of A2 toxin (NTX) employing the twitch tension assay using the mouse phrenic nerve hemidiaphragm and grip strength test in rats. The inhibitory effects on neuromuscular transmission of A2NTX at pH 7.4 and pH 6.8 were 1.95 and 3.73 times more potent than those of A1LL, respectively. The 50% effective doses for the administered limb, the dose which caused a 50% reduction in grip strength, i.e. ED(50), of A1LL, A1NTX, and A2NTX were calculated as 0.087, 0.060, and 0.040 U/head, respectively. These doses for the contralateral limb, i.e. TD(50), of A1LL, A1NTX, and A2NTX were calculated as 6.35, 7.54, and 15.62 U/head, respectively. In addition, the time required for A2NTX-injected rats to recover the grip strength of the contralateral limb was 17 days, while that for rats injected with A1LL was 35 days. The results indicated that A2NTX is a more potent neuromuscular blocker than A1 toxins, and suggested that A2NTX will provide a preferentical therapeutic agent for neurological disorders. PMID- 21029744 TI - Distinct neuroanatomical substrates and cognitive mechanisms of figure copy performance in Alzheimer's disease and behavioral variant frontotemporal dementia. AB - Figure copy is the most common method of visual spatial assessment in dementia evaluations, but performance on this test may be multifactorial. We examined the neuroanatomical substrates of figure copy performance in 46 patients with Alzheimer's disease (AD) and 48 patients with the behavioral variant of Frontotemporal dementia (bvFTD). A group of 94 neurologically healthy controls were studied for comparison. In AD, poor figure copy correlated significantly with right parietal cortex volumes but not with right dorsolateral prefrontal cortex volumes, whereas in bvFTD, figure copy performance correlated significantly with right dorsolateral prefrontal cortex volumes and there was only a trend with right parietal cortex volumes. The cognitive processes associated with figure copy performance also differed by diagnostic group such that figure copy was associated with spatial perception and attention in AD and with spatial planning and working memory in bvFTD. Spatial planning accounted for unique variance in the figure copy performance of bvFTD even after accounting for spatial perception, attention, and working memory. These results suggest that figure copy performance in AD and bvFTD is not anatomically specific and is differentially impacted by bottom-up and top-down aspects of visual spatial processing. Alternative methods of visual spatial assessment for dementia evaluations are proposed. PMID- 21029746 TI - Two ryanodine receptor isoforms in nonmammalian vertebrate skeletal muscle: possible roles in excitation-contraction coupling and other processes. AB - The ryanodine receptor (RyR) is a Ca(2+) release channel in the sarcoplasmic reticulum in vertebrate skeletal muscle and plays an important role in excitation contraction (E-C) coupling. Whereas mammalian skeletal muscle predominantly expresses a single RyR isoform, RyR1, skeletal muscle of many nonmammalian vertebrates expresses equal amounts of two distinct isoforms, alpha-RyR and beta RyR, which are homologues of mammalian RyR1 and RyR3, respectively. In this review we describe our current understanding of the functions of these two RyR isoforms in nonmammalian vertebrate skeletal muscle. The Ca(2+) release via the RyR channel can be gated by two distinct modes: depolarization-induced Ca(2+) release (DICR) and Ca(2+)-induced Ca(2+) release (CICR). In frog muscle, alpha RyR acts as the DICR channel, whereas beta-RyR as the CICR channel. However, several lines of evidence suggest that CICR by beta-RyR may make only a minor contribution to Ca(2+) release during E-C coupling. Comparison of frog and mammalian RyR isoforms highlights the marked differences in the patterns of Ca(2+) release mediated by RyR1 and RyR3 homologues. Interestingly, common features in the Ca(2+) release patterns are noticed between beta-RyR and RyR1. We will discuss possible roles and significance of the two RyR isoforms in E-C coupling and other processes in nonmammalian vertebrate skeletal muscle. PMID- 21029747 TI - A fluorescence resonance energy transfer-based fluorometer assay for screening anti-coxsackievirus B3 compounds. AB - In view of the need to develop a simple and rapid method to screen for antiviral therapeutic agents, a fluorescence resonance energy transfer (FRET)-based reporter system consisting of engineered mammalian cells expressing a cyan fluorescent protein-yellow fluorescent protein (CFP-YFP) pair linked by a short peptide containing the cleavage site of viral protease 2A (2A(pro)) was developed. By detecting the 2A(pro) produced early during the virus infection cycle, the CFP-YFP pair effectively identifies infectious coxsackievirus B3 (CVB3), a picornavirus that causes viral myocarditis in humans. The reporter system was used to screen a library of 2000 drugs and natural products for potential antiviral compounds. The reporter cells were treated with the test compounds, challenged with CVB3, and then examined using a fluorometer at 24h post-infection. Sixty-four compounds, mostly therapeutic drugs, antimicrobial compounds and compounds with unknown functions, caused at least 50% inhibition of 2A(pro) activity. Three known antiviral compounds, cosmosiin, ribavirin and baicalein, were also identified in the screening. The developed method is an effective strategy for rapid screening, and identifies compounds that inhibit CVB3 2A(pro). This method should be a valuable aid in the antiviral drug discovery effort. PMID- 21029748 TI - One-step real-time reverse transcription-PCR assays for detecting and subtyping pandemic influenza A/H1N1 2009, seasonal influenza A/H1N1, and seasonal influenza A/H3N2 viruses. AB - Pandemic influenza A/H1N1 2009 (A/H1N1pdm) virus has caused significant outbreaks worldwide. A previous one-step real-time reverse transcription-PCR (rRT-PCR) assay for detecting A/H1N1pdm virus (H1pdm rRT-PCR assay) was improved since the former probe had a low melting temperature and low tolerance to viral mutation. To help with the screening of the A/H1N1pdm virus, rRT-PCR assays were also developed for detecting human seasonal A/H1N1 (H1 rRT-PCR assay) and A/H3N2 influenza viruses (H3 rRT-PCR assay). H1pdm, H1, and H3 rRT-PCR assays were evaluated using in vitro-transcribed control RNA, isolated viruses, and other respiratory pathogenic viruses, and were shown to have high sensitivity, good linearity (R(2)=0.99), and high specificity. In addition, the improved H1pdm rRT PCR assay could detect two viral strains of A/H1N1pdm, namely, A/Aichi/472/2009 (H1N1)pdm and A/Sakai/89/2009 (H1N1)pdm, which have mutation(s) in the probe binding region of the hemagglutinin gene, without loss of sensitivity. Using the three rRT-PCR assays developed, 90 clinical specimens collected between May and October 2009 were then tested. Of these, 26, 20, and 2 samples were identified as positive for A/H1pdm, A/H3, and A/H1, respectively, while 42 samples were negative for influenza A viruses. The present results suggest that these highly sensitive and specific H1pdm, H1, and H3 rRT-PCR assays are useful not only for diagnosing influenza viruses, but also for the surveillance of influenza viruses. PMID- 21029749 TI - Double-antigen sandwich ELISA for the detection of anti-hepatitis C virus antibodies. AB - A double-antigen sandwich ELISA was developed a detection of HCV antibodies by a recombinant multi-epitope HCV antigen and a biotin-streptavidin amplification system. Three plasma specimens from 1708 individuals who were suspected previously to be HCV-positive using an HCV antibody diagnostic kit (Chuangxin, Xiamen, China) displayed negative results when using the ELISA. These results were validated by a recombinant immunoblotting assay (two were negative, and one was indeterminate). Among 889 blood specimens donated for clinical evaluation, 246 were positive and 630 were negative using the ELISA. The sensitivity and specificity of the ELISA were 98.7% and 100%, respectively. In 43 donors and 14 patients with chronic hepatitis C, the detectable rates for HCV IgM by both ELISA and the HCV anti-IgM detection reagents (Huimin, Shenyang, China) were 100%, and the detectable rate for HCV IgG using an indirect HCV-antibody detection kit (GWK, Beijing, China) was 98.3%. Thus, the double-antigen sandwich ELISA exhibits strong specificity and sensitivity and has been approved by the China State Food and Drug Administration (SFDA). The performance of the double-antigen sandwich ELISA was similar to the Ortho ELISA 3.0. It did not give false-negative results otherwise IgM was undetectable using an indirect HCV-antibody detection kit. This ELISA provides another method for the detection of HCV antibodies. PMID- 21029750 TI - Detection of infectious myonecrosis virus using monoclonal antibody specific to N and C fragments of the capsid protein expressed heterologously. AB - The gene encoding the capsid protein in ORF1 of the genome of infectious myonecrosis virus (IMNV) (GenBank AY570982) was amplified into three parts named CP-N (nucleotides 2248-3045), CP-I (nucleotides 3046-3954) and CP-C (nucleotides 3955-4953). The CP-N fragment was inserted into expression vector pTYB1 while CP I and CP-C were each inserted into expression vector pGEX-6P-1 for transformation of BL21 E. coli strain. After induction, intein-CP-N (84 kDa), glutathione-S transferase (GST)-CP-I (60 kDa) and GST-CP-C (62 kDa) fusion proteins were produced. They were separated by SDS-PAGE and electroeluted before immunization of Swiss mice for monoclonal antibody (MAb) production. Two MAbs specific to CP-N and one MAb specific to CP-C were selected for use for detection of natural IMNV infections in Penaeus vannamei by dot blotting, Western blotting and immunohistochemistry. There was no cross-reaction with shrimp tissues or common shrimp viruses including white spot syndrome virus (WSSV), yellow head virus (YHV), Taura syndrome virus (TSV), Penaeus monodon nucleopolyhedrovirus (PemoNPV), Penaeus stylirostris densovirus (PstDNV) and Penaeus monodon densovirus (PmDNV). The detection sensitivities of the MAbs were approximately 6 fmol/spot of purified recombinant intein-CP-N protein and 8 fmol/spot of GST-CP-C as determined by dot blotting. A combination of all three MAbs resulted in a twofold increase in sensitivity over use of any single MAb. However, this sensitivity was approximately 10 times lower than that of one-step RT-PCR using the same sample. Immunohistochemical analysis using MAbs specific to CP-N and CP C in IMNV-infected shrimp revealed intense staining patterns in muscles, the lymphoid organ, gills, the heart, hemocytes and connective tissue. PMID- 21029751 TI - Real time PCR method for simultaneous detection, quantitation and differentiation of capripoxviruses. AB - The genus Capripoxvirus (CaPV) comprises three members namely, sheep poxvirus (SPPV), goat poxvirus (GTPV) and lumpy skin disease virus (LSDV) affecting sheep, goats and cattle, respectively. CaPV infections produce similar symptoms in sheep and goats, and the three viruses cannot be distinguished serologically. Since there are conflicting opinions regarding the host specificity of CaPVs, particularly for goatpox and sheeppox viruses, the development of rapid genotyping tools will facilitate more accurate disease diagnosis and surveillance for better management of capripox outbreaks. This paper describes a species specific, real time polymerase chain reaction (PCR), based on unique molecular markers that were found in the G-protein-coupled chemokine receptor (GPCR) gene sequences of CaPVs, that uses dual hybridization probes for their simultaneous detection, quantitation and genotyping. The assay can differentiate between CaPV strains based on differences in the melting point temperature (Tm) obtained after fluorescence melting curve analysis (FMCA). It is highly sensitive and presents low intra- and inter-run variation. This real time PCR assay will make a significant contribution to CaPV diagnosis and to the better understanding of the epidemiology of CaPVs by enabling rapid genotyping and gene-based classification of viral strains and unequivocal identification of isolates. PMID- 21029752 TI - Multiplex PCR for rapid detection of serotype A foot-and-mouth disease virus variants with amino acid deletion at position 59 of the capsid protein VP3. AB - In India, there has been co-circulation, extinction and emergence of genotypes/lineages within serotype A foot-and-mouth disease (FMD) virus. At present an antigenically heterogeneous, unique lineage within genotype VII dominates the field outbreaks. This genetic cluster has amino acid deletion at position 59 of VP3 (VP3(59)-deletion group), considered to be critical antigenically. The emergence of this group warrants rapid and accurate detection to facilitate early planning and implementation of an effective control policy. A rapid multiplex PCR assay was developed for detection of the dominating VP3(59) deletion group with 100% sensitivity and specificity, even before generating sequence data and confirmatory phylogenetic analysis. This development is important for surveillance of FMD in India. PMID- 21029753 TI - The importin beta binding domain as a master regulator of nucleocytoplasmic transport. AB - Specific and efficient recognition of import cargoes is essential to ensure nucleocytoplasmic transport. To this end, the prototypical karyopherin importin beta associates with import cargoes directly or, more commonly, through import adaptors, such as importin alpha and snurportin. Adaptor proteins bind the nuclear localization sequence (NLS) of import cargoes while recruiting importin beta via an N-terminal importin beta binding (IBB) domain. The use of adaptors greatly expands and amplifies the repertoire of cellular cargoes that importin beta can efficiently import into the cell nucleus and allows for fine regulation of nuclear import. Accordingly, the IBB domain is a dedicated NLS, unique to adaptor proteins that functions as a molecular liaison between importin beta and import cargoes. This review provides an overview of the molecular role played by the IBB domain in orchestrating nucleocytoplasmic transport. Recent work has determined that the IBB domain has specialized functions at every step of the import and export pathway. Unexpectedly, this stretch of ~40 amino acids plays an essential role in regulating processes such as formation of the import complex, docking and translocation through the nuclear pore complex (NPC), release of import cargoes into the cell nucleus and finally recycling of import adaptors and importin beta into the cytoplasm. Thus, the IBB domain is a master regulator of nucleocytoplasmic transport, whose complex molecular function is only recently beginning to emerge. This article is part of a Special Issue entitled: Regulation of Signaling and Cellular Fate through Modulation of Nuclear Protein Import. PMID- 21029755 TI - Expression, purification and characterization of cloning-grade zinc finger nuclease. AB - The limited number of naturally occurring rare-cutting restriction enzymes and the slow and tedious engineering of existing restriction enzymes for novel specificities have prompted the design of new strategies for the development of restriction enzymes with specificities for long DNA sequences. One possibility is using zinc finger nucleases (ZFNs)-synthetic restriction enzymes that are custom designed to target and cleave long DNA sequences and which have been recently shown useful for DNA cloning. Here we report on the purification and biochemical analysis of ZFN-10, a custom-made ZFN. We show that Ni-affinity and gel filtration purification methods are sufficient to produce a cloning-grade enzyme. We show that ZFN-10 can function as an accurate and reliable ZFN using the same reagents and protocols used for naturally occurring and commercially available recombinant restriction enzymes. We also show that ZFN-10 tolerates a set of target-site substitutions which can be predicted from the specificities of recognition helices incorporated into the structure of its DNA-binding domain. The relative simplicity of ZFN-10 design, expression, purification and analysis suggests that novel ZFNs can potentially be designed and applied for various recombinant DNA applications. PMID- 21029756 TI - Action of xylan deacetylating enzymes on monoacetyl derivatives of 4-nitrophenyl glycosides of beta-D-xylopyranose and alpha-L-arabinofuranose. AB - Measurements of esterase activity by enzyme-coupled assays on monoacetates of 4 nitrophenyl beta-D-xylopyranoside and 4-nitrophenyl alpha-L-arabinofuranoside showed that acetylxylan esterases of families 1, 4 and 5 produced by Trichoderma reesei and Penicillium purpurogenum have a strong preference for deacetylation of position 2 in xylopyranosides. The acetylxylan esterases exhibit only weak activity on acetylated arabinofuranosides, with 2-acetate as the best substrate. Acetyl esterases of family 16 produced by the same two fungi deacetylate in xylopyranosides preferentially positions 3 and 4. Their specific activity on arabinofuranosides is also much lower than on xylopyranosides, however, substantially greater than that in the case of typical acetylxylan esterases. PMID- 21029757 TI - Metabolic relationship between polyhydroxyalkanoic acid and rhamnolipid synthesis in Pseudomonas aeruginosa: comparative 13C NMR analysis of the products in wild type and mutants. AB - Polyhydroxyalkanoic acids (PHAs) and rhamnolipids considered as biotechnologically important compounds are simultaneously produced by Pseudomonas aeruginosa. Both are synthesized from common precursors, (R)-3-hydroxyfatty acids. To find the probable metabolic relationship between their syntheses, we investigated the PHA and rhamnolipids production in four pha (phaC1, phaC2, phaZ, and phaG), four rhl (rhlA, rhlB, rhlR, and rhlI) and rpoS mutant strains of P. aeruginosa PA14 and PAO1 grown in minimal medium containing 70 mM fructose or 30 mM decanoic acid. Higher PHA accumulation was found in the rhamnolipid-negative mutants than in the wild-type strains, suggesting that 3-hydroxyfatty acid precursors become more available for PHA synthesis when rhamnolipids synthesis is absent. However, compared to the wild-type strains, rhamnolipids production was not enhanced in the four pha mutants of P. aeruginosa PA14 and PAO1 which indicates that rhamnolipids production in P. aeruginosa could be tightly regulated at the transcriptional level by a quorum-sensing response. The metabolic pathways for PHA and rhamnolipid synthesis from medium-chain-length fatty acids were also investigated using octanoic-1-13C acid. 13C NMR analysis revealed that the monomer-unit (R)-3-hydroxyoctanoate-1-13C being converted from the octanoic acid substrate was effectively incorporated into PHA. In the rhamnolipid synthesis, the (R)-3-hydroxyoctanoate-1-13C is suggested to be firstly converted to (R)-3-hydroxydecanoate-1,3-13C via fatty acid de novo biosynthesis pathway and then further processed into (R)-3-((R)-3 hydroxyalkanoyloxy)alkanoic acids (HAAs) via RhlA. The ratio of mono- to dirhamnolipids in the product depended on the type of carbon sources. The rhlB mutant could be exploited as an efficient producer of the important biosurfactant HAAs (e.g., ~700 mg/L HAAs was obtained when grown on 60 mM octanoic acid). PMID- 21029758 TI - Susceptibility and production of a feline endogenous retrovirus (RD-114 virus) in various feline cell lines. AB - RD-114 virus is a replication-competent feline endogenous retrovirus that has been classified as a xenotropic virus. In this study, we examined the expression of the receptors for RD-114 virus in feline cell lines by conducting a pseudotype virus infection assay. Six out of eight feline cell lines were susceptible to the RD-114 pseudotype virus and two cell lines (MCC and FER cells) were resistant. The two resistant cell lines and one cell line (CRFK cells) weakly sensitive to the RD-114 pseudotype virus were found to produce replication-competent RD114 like viruses by the LacZ marker rescue assay and the interference assay. These data strongly suggest that RD-114 virus is polytropic and resistance to RD-114 virus in certain cell lines is due to receptor interference but not polymorphism of the RD-114 receptors. In addition, we determined the amino acid sequences of the envelope region of RD-114-like viruses produced from MCC, FER and CRFK cells. The sequences were identical with the authentic RD-114 virus. Because many feline cell lines are used to manufacture live attenuated vaccines for companion animals, attention should be paid to contamination of the RD-114 virus in vaccines. PMID- 21029759 TI - Consumer satisfaction with pork meat and derived products in five European countries. AB - This paper investigates consumers' satisfaction level with pork meat and derived products in five European countries. Data were collected through a cross sectional web-based survey in Belgium, Denmark, Germany, Greece, and Poland during January 2008 with a total sample of 2437 consumers. Data included socio demographics and questions regarding satisfaction with 27 common pork-based products; classified into fresh pork, processed pork and pork meat products. Satisfaction was evaluated in terms of overall satisfaction, as well as satisfaction with health-giving qualities, price, convenience and taste. Logistic regression analyses showed taste as the main determinant of satisfaction, followed by convenience. Healthfulness is not a significant driver of overall satisfaction. Price influences satisfaction with fresh pork more than with processed products. Tasty pork, easy to prepare and consume, with adequate promotion of its healthfulness, and with a good price/quality relationship appears to be the key factor to satisfy pork consumers. PMID- 21029754 TI - Nuclear import by karyopherin-betas: recognition and inhibition. AB - Proteins in the karyopherin-beta family mediate the majority of macromolecular transport between the nucleus and the cytoplasm. Eleven of the 19 known human karyopherin-betas and 10 of the 14S. cerevisiae karyopherin-betas mediate nuclear import through recognition of nuclear localization signals or NLSs in their cargos. This receptor-mediated process is essential to cellular viability as proteins are translated in the cytoplasm but many have functional roles in the nucleus. Many known karyopherin-beta-cargo interactions were discovered through studies of the individual cargos rather than the karyopherins, and this information is thus widely scattered in the literature. We consolidate information about cargos that are directly recognized by import-karyopherin-betas and review common characteristics or lack thereof among cargos of different import pathways. Knowledge of karyopherin-beta-cargo interactions is also critical for the development of nuclear import inhibitors and the understanding of their mechanisms of inhibition. This article is part of a Special Issue entitled: Regulation of Signaling and Cellular Fate through Modulation of Nuclear Protein Import. PMID- 21029760 TI - Distribution and characterization of Corazonin in the central nervous system of Triatoma infestans (Insecta: Heteroptera). AB - The distribution of corazonin in the central nervous system of the heteropteran insect Triatoma infestans was studied by immunohistochemistry. The presence of corazonin isoforms was investigated using MALDI-TOF mass spectrometry in samples containing the brain, the subesophageal ganglion, the corpora cardiaca-corpus allatum complex and the anterior part of the aorta. Several groups of immunopositive perikarya were detected in the brain, the subesophageal ganglion and the thoracic ganglia. Regarding the brain, three clusters were observed in the protocerebrum. One of these clusters was formed by somata located near the entrance of the ocellar nerves whose fibers supplied the aorta and the corpora cardiaca. The remaining groups of the protocerebrum were located in the lateral soma cortex and at the boundary of the protocerebrum with the optic lobe. The optic lobe housed immunoreactive somata in the medial soma layer of the lobula and at the level of the first optic chiasma. The neuropils of the deutocerebrum and the tritocerebrum were immunostained, but no immunoreactive perikarya were detected. In the subesophageal ganglion, immunostained somata were found in the soma layers of the mandibular and labial neuromeres, whereas in the mesothoracic ganglionic mass, they were observed in the mesothoracic, metathoracic and abdominal neuromeres. Immunostained neurites were also found in the esophageal wall. The distribution pattern of corazonin like immunoreactivity in the central nervous system of this species suggests that corazonin may act as a neurohormone. Mass spectrometric analysis revealed that [Arg(7)]-corazonin was the only isoform of the neuropeptide present in T. infestans tissue samples. PMID- 21029761 TI - Meeting report: Guanosines and quadruplexes (London, September 15-17, 2010). AB - The meeting entitled "Guanosines and quadruplexes" was held in London on September 2010. It attracted over 80 participants from all over the world, combining researchers interested in nucleoside/nucleotide self-assembly and nucleic acids structures, working in fields ranging from chemistry, biology, physics, theory to material sciences and nanotechnology. PMID- 21029762 TI - Effects of intrinsic pleasantness and goal conduciveness appraisals on somatovisceral responding: Somewhat similar, but not identical. AB - In the emotion literature, appraisals of an event's pleasantness and goal conduciveness are often considered as interchangeable and subsumed under the term valence. Some appraisal theories, however, emphasize that there is a conceptual difference between these two appraisals. With the current study, we investigated whether such a conceptual difference would be reflected in different somatovisceral response profiles for intrinsic pleasantness and goal conduciveness. Participants viewed unpleasant and pleasant pictures (intrinsic pleasantness) and performed either goal conducive (i.e., decreasing the size of unpleasant pictures, increasing the size of pleasant pictures) or goal obstructive (i.e., increasing the size of unpleasant pictures, decreasing the size of pleasant pictures) arm movements. Our data suggest that the two appraisals have somewhat similar, but not identical, response patterns. Thus, our results emphasize the importance of distinguishing between intrinsic pleasantness and goal conduciveness. Moreover, we find evidence that the efferent effects of the two appraisals combine multiplicatively, and that predictability of goal conduciveness may influence the impact of goal conduciveness appraisals on somatovisceral responding. PMID- 21029763 TI - A minimal mathematical model of nonphotochemical quenching of chlorophyll fluorescence. AB - Under natural conditions, plants are exposed to rapidly changing light intensities. To acclimate to such fluctuations, plants have evolved adaptive mechanisms that optimally exploit available light energy and simultaneously minimise damage of the photosynthetic apparatus through excess light. An important mechanism is the dissipation of excess excitation energy as heat which can be measured as nonphotochemical quenching of chlorophyll fluorescence (NPQ). In this paper, we present a highly simplified mathematical model that captures essential experimentally observed features of the short term adaptive quenching dynamics. We investigate the stationary and dynamic behaviour of the model and systematically analyse the dependence of characteristic system properties on key parameters such as rate constants and pool sizes. Comparing simulations with experimental data allows to derive conclusions about the validity of the simplifying assumptions and we further propose hypotheses regarding the role of the xanthophyll cycle in NPQ. We envisage that the presented theoretical description of the light reactions in conjunction with short term adaptive processes serves as a basis for the development of more detailed mechanistic models by which the molecular mechanisms of NPQ can be theoretically studied. PMID- 21029764 TI - Neuromuscular pathology in mice lacking alpha-synuclein. AB - This work was undertaken in order to study the possible role of alpha-synuclein in the function of the neuro-muscular junction in skeletal muscles. Repeated stimulation of skeletal muscle motor neurons revealed signs of neuromuscular pathology in alpha-synuclein null mutated (C57Bl/6JOlaHsd) and knockout (B6;129X1 Snca(tm1Rosl)/J) mice. This stimulation produced repetitive compound muscle action potentials in both lines of alpha-synuclein deficient mice. Muscle strength and muscle coordination during ambulation were unaffected, though motor learning was slower in alpha-synuclein deficient mice in the Rotarod test. We conclude that alpha-synuclein may play a role in acetylcholine compartmentalization at the neuromuscular junction, and in the fine control of activity of skeletal muscles. PMID- 21029765 TI - Association between CAG repeat length in the PPP2R2B gene and Alzheimer disease in the Japanese population. AB - We analyzed the association between PPP2R2B gene CAG repeat length and Alzheimer disease (AD) susceptibility in the Japanese population. Blood samples were collected from 218 late-onset AD patients and 86 controls. DNA fragments containing the target CAG repeat region were amplified using polymerase chain reaction (PCR). PCR products were sequenced using ABI PRISM 310 genetic analyzer. The mean CAG repeat length did not differ significantly between the control and AD groups. In contrast, the frequency of CAG repeats shorter than 15 was significantly higher in AD group, specifically in the AD with APOE4 subgroup, than in the control group. The results suggest that CAG repeat lengths in the PPP2R2B gene may be potential genetic markers for AD susceptibility in the Japanese population. PMID- 21029766 TI - Spotting the right location- imaging approaches to resolve the intracellular localization of invasive pathogens. AB - BACKGROUND: A common strategy of microbial pathogens is to invade host cells during infection. The invading microbes explore different intracellular compartments to find their preferred niche. SCOPE OF REVIEW: Imaging has been instrumental to unravel paradigms of pathogen entry, to identify their exact intracellular location, and to understand the underlying mechanisms for the formation of pathogen-containing niches. Here, we provide an overview of imaging techniques that have been applied to monitor the intracellular lifestyle of pathogens, focusing mainly on bacteria that either remain in vacuolar-bound compartments or rupture the endocytic vacuole to escape into the host's cellular cytoplasm. MAJOR CONCLUSIONS: We will depict common molecular and cellular paradigms that are preferentially exploited by pathogens. A combination of electron microscopy, fluorescence microscopy, and time-lapse microscopy has been the driving force to reveal underlying cell biological processes. Furthermore, the development of highly sensitive and specific fluorescent sensor molecules has allowed for the identification of functional aspects of niche formation by intracellular pathogens. GENERAL SIGNIFICANCE: Currently, we are beginning to understand the sophistication of the invasion strategies used by bacterial pathogens during the infection process- innovative imaging has been a key ingredient for this. This article is part of a Special Issue entitled Nanotechnologies - Emerging Applications in Biomedicine. PMID- 21029767 TI - Design of novel 2D and 3D biointerfaces using self-organization to control cell behavior. AB - BACKGROUND: The design of biocompatible 2D surfaces and 3D nano/micro topographies based on self-organization has a variety of potential applications in medical devices and tissue engineering. We have reported that biocompatible 2D surface using poly(2-methoxyethyl acrylate) (PMEA) and honeycomb-patterned 3D films with regular interconnected pores that is formed by self-organization. SCOPE OF REVIEW: We highlight that 1) the reasons for this compatibility by comparing the structure of water in hydrated PMEA to the water structure of other polymers and 2) the reasons that 3D films exerted a strong influence on normal, cancer and stem cell morphology, proliferation, differentiation, cytoskeleton, focal adhesion, and functions including matrix production profiles. MAJOR CONCLUSIONS: 1) We hypothesized that intermediate water, which prevents the biocomponents from directly contacting the polymer surface or non-freezing water on the polymer surface, plays an important role in the excellent biocompatibility. 2) The cellular response to 3D films originates from the regularly aligned adsorbed proteins determined by the pore structure of the film. GENERAL SIGNIFICANCE: It is expected that combining the biocompatible 2D surfaces and 3D nano/micro topographies will provide an effective strategy for medical devices and tissue engineering scaffolds. This article is part of a Special Issue entitled Nanotechnologies - Emerging Applications in Biomedicine. PMID- 21029768 TI - Anti-malarial herbal remedies of northeast India, Assam: an ethnobotanical survey. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Malaria is a serious public health problem in the north-eastern region of India including Assam, in view of development of chloroquine resistant Plasmodium falciparum. There is need for alternative and affordable therapy. AIM OF THE STUDY: This study was conducted to document indigenous knowledge, usage customs and practices of medicinal plant species traditionally used by the residents of Sonitpur district of Tezpur, Assam to treat malaria and its associated symptoms. MATERIALS AND METHODS: A total of 50 randomly selected sampling represented by male (38.76%) and female respondents (12.24%) were interviewed using a semi-structured questionnaire. RESULTS: The present ethno-botanical survey revealed 22 species of plants belonging to 17 botanical families were reported to be used exclusively in this region for the treatment of malaria. Verbenaceae (three species), Menispermaceae (two species), and Acanthaceae (two species) botanical families represented the species that are most commonly cited in this survey work and the detailed use of plants has been collected and described. CONCLUSIONS: The most serious threat to the existing knowledge and practice on traditional medicinal plants included cultural change, particularly the influence of modernization and lack of interests shown by the next younger generations were the main problems reported by the informants during the field survey. Hence, the proper documentation of traditional medicinal plants being used as anti-malarial agents and related indigenous knowledge held by the tribal community is an important approach to control the spread of vector-borne diseases like malaria reported in this survey work. PMID- 21029769 TI - Protective effect of Ilex latifolia, a major component of "kudingcha", against transient focal ischemia-induced neuronal damage in rats. AB - AIMS OF THE STUDY: Ilex latifolia (Aquifoliaceae), a primary component of "kudingcha", has been used in Chinese folk medicine to treat various kinds of diseases including headaches, inflammatory diseases, and cardiac ischemic injury. The present study investigated the protective effect of the ethanol extract of Ilex latifolia against transient, focal, ischemia-induced neuronal damage. MATERIALS AND METHODS: Transient focal ischemia was induced by 2 h middle cerebral artery occlusion followed by 24 h reperfusion (MCAO/reperfusion) in rats. After MCAO/reperfusion, brain infarction and neuronal death were measured by triphenyltetrazolium chloride and hematoxylin and eosin staining, respectively. Glutathione concentration and lipid peroxidation rate were measured. The expression levels of phosphorylated mitogen activated proteins kinases (MAPKs), cyclooxygenase 2 (COX-2), and anti-apoptotic and pro-apoptotic proteins were detected by Western blot. RESULTS: Ilex latifolia (50-200 mg/kg) significantly reduced MCAO/reperfusion-induced infarction and edema formation, neurological deficits, and brain cell death. Depletion of glutathione level and lipid peroxidation induced by MCAO/reperfusion were inhibited by administration of Ilex latifolia. The increase of phosphorylated MAPKs, COX-2, and proapoptotic proteins and the decrease of antiapoptotic protein in MCAO/reperfusion rats were significantly inhibited by treatment with Ilex latifolia. CONCLUSION: Ilex latifolia ameliorated ischemic injury induced by MCAO/reperfusion in rats, and this neuroprotective effect might be associated with its anti-apoptotic effect, resulting from anti-oxidative and anti-inflammatory actions. PMID- 21029770 TI - Suppressive effect of Petasites japonicus extract on ovalbumin-induced airway inflammation in an asthmatic mouse model. AB - AIM OF THE STUDY: Asthma is a disease marked by airway inflammation. Petasites japonicus (Pj) is known as an herb for treating asthma, oxidant stress and gastric ulcer in traditional Oriental medicine. In this study, the inhibitory effects of Pj extract on asthmatic responses were examined both in vitro and in vivo. MATERIALS AND METHODS: The Pj extract was acquired from whole plants of Petasites japonicus using 80% ethanol. Cytotoxicity of the Pj extract on Jurkat cells and THP-1 cells was determined using MTT assay. ELISA was performed to determine the expression levels of cytokines, chemokines, and IgE. BALB/c mice were used for an OVA-induced asthmatic mouse model. Reactive oxygen species (ROS) production was stained with 2',7'-dichlorofluorescein diacetate and measured by fluorescence-activated cell sorting analysis. The effects of the Pj extract on leukocyte infiltration and mucus production were determined using periodic acid Schiff staining as well as hematoxylin and eosin staining. RESULTS: The Pj extract inhibits the increased release of interleukin (IL)-2, IL-4, IL-5, IL-13, and TNF-alpha due to house dust mite in Jurkat cells and blocks IL-6 expression in THP-1 cells without cytotoxicity. In the asthmatic mouse model, the Pj extract inhibits eosinophil infiltration, mucus hypersecretion, and IL-5 level in bronchoalveolar lavage (BAL) fluid, and it has a scavenging effect on ROS production of cells in BAL fluid. CONCLUSION: The Pj extract has suppressive properties for the pathogenesis of airway inflammation and may be used as a potent agent for the treatment of asthma. PMID- 21029771 TI - Extracts of Arisaema rhizomatum C.E.C. Fischer attenuate inflammatory response on collagen-induced arthritis in BALB/c mice. AB - AIM OF THE STUDY: Arisaema rhizomatum C.E.C. Fischer (ARCF), called as "Xuelijian", a local herb just growing in China, has been used as a traditional ethnic Chinese medicine for long because of its remarkable activity to alleviate pain and inflammation for patients suffering from rheumatism among the people with weak side-effect. However, rare study on the anti-arthritic activity of ARCF has been reported in vivo. The aim of this study is to investigate the protective effect of the herb on collagen-induced arthritis in mice and explore the potential immunological mechanisms. MATERIALS AND METHODS: CIA was induced in male BALB/c mice by been subcutaneously injected type II bovine collagen (CII) for twice. The combined MeOH extract (ME) of ARCF rhizome was successively partitioned into four fractions with petroleum ether (PE), ethyl acetate (EE), n butyl alcohol (n-BE) and water (WE). After the second collagen immunization, mice were administered orally with different doses of ME, EE and n-BE (ME 130, 261, 522 mg kg(-1); EE 10.2, 20.4, 40.8 mg kg(-1); n-BE 52, 104, 208 mg kg(-1)) every other day for 3 weeks. The progression of edema of paws and knee joints was inspected by using a vernier calliper every 3 days from the 10th day after the first injection to the end of the experiment. The spleen index was measured and the knee joint destruction was observed by pathological sections. Levels of inflammatory cytokines including tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1beta), interleukin-6 (IL-6), interleukin-33 (IL-33 or IL 1F11) and rheumatoid factor (RF) in serum were measured by ELISA. RESULTS: Administration of ME, EE and n-BE significantly suppressed paws and joints swelling and reduced the spleen indexes. Pathological examination demonstrated that ARCF effectively protected anklebone and cartilage from being eroded versus vehicle-treated mice. Moreover, the serum levels of inflammatory cytokines TNF alpha, IL-1beta, IL-6, IL-33 and RF were markedly lowered in ARCF treated groups compared with the control group (p<0.05). CONCLUSION: Our studies demonstrate that administration of ARCF is obviously suppressed the progression of CIA. The anti-arthritic effectiveness of ARCF will make the herb a strong candidate for further clinical trials on RA patients. PMID- 21029772 TI - Genomic DNA extraction from whole blood stored from 15- to 30-years at -20 degrees C by rapid phenol-chloroform protocol: a useful tool for genetic epidemiology studies. AB - Long-term stored (LTS) whole blood collection can be an important source of DNA without collection costs, but there is a lack of information on methods useful to extract genomic DNA from such type of biological material. Here we report a simple and fast revisited phenol/chloroform extraction method from LTS whole blood. Protocol reliability was assessed by comparison with proteinase K and silica-gel membrane spin column-based DNA extraction methods using LTS -20 degrees C whole blood from 1980, and by testing it on 82 whole blood samples, collected from 1980 to 1995, with high quality (A(260/280) = 1.79 +/- 0.32 O.D., A(260/230) = 1.45 +/- 0.52 O.D.) and quantity results. Genotyping efficiency was also checked by performing RFLP-PCR and ASP-PCR of p53 Pro72Arg (rs1042522) SNP and hTERT MNS16A VNTR, respectively, resulting in 100% of samples successfully typed. In addition to the goodness and the efficiency of method proposed here, this protocol achieves working time reduction combining extraction and purification steps, allowing to work at room temperature. Furthermore, phenol is able to inactivate any potential nuclease and potential infective sources from the first step on. Based on these results we also conclude that LTS -20 degrees C whole blood samples may be considered a reliable and potential resource for future genotyping studies and retrospective analysis in a genetic epidemiological setting. PMID- 21029774 TI - Iron loading-induced aggregation and reduction of iron incorporation in heteropolymeric ferritin containing a mutant light chain that causes neurodegeneration. AB - Hereditary ferritinopathy (HF) is a neurodegenerative disease characterized by intracellular ferritin inclusion bodies (IBs) and iron accumulation throughout the central nervous system. Ferritin IBs are composed of mutant ferritin light chain as well as wild-type light (Wt-FTL) and heavy chain (FTH1) polypeptides. In vitro studies have shown that the mutant light chain polypeptide p.Phe167SerfsX26 (Mt-FTL) forms soluble ferritin 24-mer homopolymers having a specific structural disruption that explains its functional problems of reduced ability to incorporate iron and aggregation during iron loading. However, because ferritins are usually 24-mer heteropolymers and all three polypeptides are found in IBs, we investigated the properties of Mt-FTL/FTH1 and Mt-FTL/Wt-FTL heteropolymeric ferritins. We show here the facile assembly of Mt-FTL and FTH1 subunits into soluble ferritin heteropolymers, but their ability to incorporate iron was significantly reduced relative to Wt-FTL/FTH1 heteropolymers. In addition, Mt FTL/FTH1 heteropolymers formed aggregates during iron loading, contrasting Wt FTL/FTH1 heteropolymers and similar to what was seen for Mt-FTL homopolymers. The resulting precipitate contained both Mt-FTL and FTH1 polypeptides as do ferritin IBs in patients with HF. The presence of Mt-FTL subunits in Mt-FTL/Wt-FTL heteropolymers also caused iron loading-induced aggregation relative to Wt-FTL homopolymers, with the precipitate containing Mt- and Wt-FTL polypeptides again paralleling HF. Our data demonstrate that co-assembly with wild-type subunits does not circumvent the functional problems caused by mutant subunits. Furthermore, the functional problems characterized here in heteropolymers that contain mutant subunits parallel those problems previously reported in homopolymers composed exclusively of mutant subunits, which strongly suggests that the structural disruption characterized previously in Mt-FTL homopolymers occurs in a similar manner and to a significant extent in both Mt-FTL/FTH1 and Mt FTL/Wt-FTL heteropolymers. PMID- 21029773 TI - Discovery-driven research and bioinformatics in nuclear receptor and coregulator signaling. AB - Nuclear receptors (NRs) are a superfamily of ligand-regulated transcription factors that interact with coregulators and other transcription factors to direct tissue-specific programs of gene expression. Recent years have witnessed a rapid acceleration of the output of high-content data platforms in this field, generating discovery-driven datasets that have collectively described: the organization of the NR superfamily (phylogenomics); the expression patterns of NRs, coregulators and their target genes (transcriptomics); ligand- and tissue specific functional NR and coregulator sites in DNA (cistromics); the organization of nuclear receptors and coregulators into higher order complexes (proteomics); and their downstream effects on homeostasis and metabolism (metabolomics). Significant bioinformatics challenges lie ahead both in the integration of this information into meaningful models of NR and coregulator biology, as well as in the archiving and communication of datasets to the global nuclear receptor signaling community. While holding great promise for the field, the ascendancy of discovery-driven research in this field brings with it a collective responsibility for researchers, publishers and funding agencies alike to ensure the effective archiving and management of these data. This review will discuss factors lying behind the increasing impact of discovery-driven research, examples of high-content datasets and their bioinformatic analysis, as well as a summary of currently curated web resources in this field. This article is part of a Special Issue entitled: Translating nuclear receptors from health to disease. PMID- 21029776 TI - New insights into the pathogenesis of chronic lymphocytic leukemia. AB - Chronic lymphocytic leukemia (CLL), an incurable disease of the elderly, stands out as unique among the malignancies derived from mature B lymphocytes. The histology, immunophenotype, immunoglobulin variable region (IgV) gene somatic hypermutation status, and the pattern of genetic alterations of the tumor cells are markedly distinct from that of any other B-cell tumor. Most notably, CLL cases can have somatically mutated as well as unmutated IgV genes which largely correlate with a favorable and unfavorable clinical prognosis, respectively. Moreover, recent evidence suggests that 6% of the normal elderly population develops a monoclonal B-cell lymphocytosis (MBL) that appears as the precursor to CLL in 1-2% of cases. Over the last decade, global gene expression profile analysis was instrumental in defining CLL as a malignancy originating from the oncogenic transformation of a common cellular precursor that resembles an antigen experienced B cell. These findings were complemented by the realization that all CLL, independent of their IgV gene somatic mutation status, express B-cell receptors (BCRs) that show evidence of antigen-experience. Indeed, the BCRs of CLL cases among different individuals can be similar to the extent that one was able to define subsets of stereotyped receptors based on the homology in the antigen-binding regions. Together, these observations strongly support the notion that antigen plays a critical role in CLL pathogenesis. This role is complemented by genetic alterations that, analogous to most cancer types, represent the initiating pathogenetic event. In fact, CLL cases display recurrent genetic aberrations including trisomy 12 and monoallelic or biallelic deletion/inactivation of chromosomal regions 17p, 11q and 13q14. However, virtually all CLL cases lack balanced reciprocal chromosomal translocations, the genetic hallmark of germinal center (GC)-derived lymphomas. The most frequent genetic aberration in CLL, deletion of chromosomal region 13q14, was recently shown to have a specific role in CLL pathogenesis. This region encodes a tumor suppressor locus comprising a microRNA cluster embedded in a long sterile RNA gene, whose deletion in the mouse leads to lymphoproliferative syndromes recapitulating the human CLL-associated spectrum, including MBL, CLL and B-cell non-Hodgkin lymphoma (B-NHL). This review will focus on the cellular origin of CLL, its relationship to the mechanisms of generating CLL-associated genetic lesions and on the role of the 13q14 deletion in CLL pathogenesis as emerging from the analysis of a newly generated mouse model. PMID- 21029775 TI - Heterogeneous intrastriatal pattern of proteins regulating axon growth in normal adult human brain. AB - There is much controversy regarding the extent of axon regeneration/sprouting ability in adult human brain. However, intrinsic differences in axon/neurite growth capability amongst striatal (caudate, putamen, nucleus accumbens) subdivisions could conceivably underlie, in part, their differential vulnerability in degenerative human brain disorders. To establish whether the distribution of axon growth markers in mature human striatum might be uniform or heterogeneous, we measured the intra-striatal pattern, in autopsied brain of normal subjects (n=40, age 18-99), of proteins involved in regulating axon growth. These proteins included polysialylated neural cell adhesion molecule (PSA NCAM), microtubule-associated proteins TUC-4 (TOAD/Ulip/CRAMP-4) and doublecortin (DCX), and Bcl-2. The distribution of the marker proteins within the striatum was heterogeneous and inversely related to the pattern of dopamine loss previously characterized in Parkinson's disease (PD), with levels in nucleus accumbens>caudate>putamen, ventral>dorsal, and rostral putamen>caudal. In contrast, distribution of glial markers including glial fibrillary acidic protein (GFAP) and human leukocyte antigens (HLA-DRalpha and HLA-DR/DQ/DPbeta), other Bcl 2 family proteins, and control proteins neuron-specific enolase and alpha-tubulin in the striatum was either homogeneous or had a pattern unmatched to dopamine loss in PD. The putamen also showed more marked age-dependent decreases in concentrations of PSA-NCAM, TUC-4, and DCX and increases in GFAP levels than caudate. We conclude that the intrastriatal pattern of several key axon growth proteins is heterogeneous in adult human brain. Further investigation will be required to establish whether this pattern, which was inversely correlated with the pattern of dopamine loss in PD, is involved to any extent in the pathophysiology of this degenerative disorder. PMID- 21029777 TI - Affinity recovery of eight HER2-binding affibody variants using an anti-idiotypic affibody molecule as capture ligand. AB - Affibody molecules generated by combinatorial protein engineering to bind the human epidermal growth factor receptor 2 (HER2) have in earlier studies proven to be promising tracers for HER2-mediated molecular imaging of cancer. Amino acid extensions either at the N- or C-terminus of these Z(HER2) affibody molecules, have been successfully employed for site-specific radiolabeling of the tracer candidates. Hexahistidyls or other tags, which would be convenient for recovery purposes, should be avoided since they could negatively influence the tumor targeting efficacy and biodistribution properties of the tracer. Using a new beta lactamase-based protein fragment complementation assay (PCA), an affibody molecule was isolated which bound a Z(HER2) affibody molecule with sub-micromolar affinity, but not unrelated affibody molecules. This suggests that the interacting area include the HER2-binding surface of Z(HER2). This novel anti idiotypic affibody molecule Z(E01) was produced in Escherichia coli, purified, and chemically coupled to a chromatography resin in order to generate an affibody based affinity column, suitable for recovery of different variants of Z(HER2) affibody molecules, having a common binding surface for HER2. Eight such Z(HER2) affibody molecules, designed for future radioimaging investigations, having different C-terminal peptide extensions aimed for radioisotope ((99m)Tc) chelation, were successfully produced and recovered in a single step to high purity using the anti-idiotypic affibody ligand for the affinity purification. These results clearly suggest a potential for the development of anti-idiotypic affibody-based resins for efficient recovery of related variants of a target protein that might have altered biochemical properties, thus avoiding the cumbersome design of specific recovery schemes for each variant of a target protein. PMID- 21029778 TI - RosettaEPR: an integrated tool for protein structure determination from sparse EPR data. AB - Site-directed spin labeling electron paramagnetic resonance (SDSL-EPR) is often used for the structural characterization of proteins that elude other techniques, such as X-ray crystallography and nuclear magnetic resonance (NMR). However, high resolution structures are difficult to obtain due to uncertainty in the spin label location and sparseness of experimental data. Here, we introduce RosettaEPR, which has been designed to improve de novo high-resolution protein structure prediction using sparse SDSL-EPR distance data. The "motion-on-a-cone" spin label model is converted into a knowledge-based potential, which was implemented as a scoring term in Rosetta. RosettaEPR increased the fractions of correctly folded models ( [Formula: see text] <7.5A) and models accurate at medium resolution ( [Formula: see text] <3.5A) by 25%. The correlation of score and model quality increased from 0.42 when using no restraints to 0.51 when using bounded restraints and again to 0.62 when using RosettaEPR. This allowed for the selection of accurate models by score. After full-atom refinement, RosettaEPR yielded a 1.7A model of T4-lysozyme, thus indicating that atomic detail models can be achieved by combining sparse EPR data with Rosetta. While these results indicate RosettaEPR's potential utility in high-resolution protein structure prediction, they are based on a single example. In order to affirm the method's general performance, it must be tested on a larger and more versatile dataset of proteins. PMID- 21029781 TI - Assessment of the cerebral cortex during motor task behaviours in adults: a systematic review of functional near infrared spectroscopy (fNIRS) studies. AB - Functional near infrared spectroscopy (fNIRS) is an emerging tool for non invasively monitoring the haemodynamic response to brain activation. The technique has been widely adopted to investigate cortical responses during motor tasks in health and disease. This systematic review provides a critical analysis of the research findings in the hope of summating relevant information, identifying consistent outcomes acquired using different spectrometers, clarifying data inconsistencies, and learning from the common challenges across disciplines. The spatiotemporal characteristics, reliability, repeatability and modulation of typical cortical response evoked by motor stimulation are all evaluated in detail. The review assesses the contribution of the technique to advancing our understanding of motor skill learning and control in the context of tasks of everyday living, athletic performance, and recovery from neurological illness. Finally, the limitations of current fNIRS technologies are examined and a series of recommendations for future studies are provided based upon the reviewed literature. PMID- 21029779 TI - The beginning of a beautiful friendship: cross-linking/mass spectrometry and modelling of proteins and multi-protein complexes. AB - After more than a decade of method development, cross-linking in combination with mass spectrometry and bioinformatics is finally coming of age. This technology now provides improved opportunities for modelling by mapping structural details of functional complexes in solution. The structure of proteins or protein complexes is ascertained by identifying amino acid pairs that are positioned in close proximity to each other. The validity of this technique has recently been benchmarked for large multi-protein complexes, by comparing cross-link data with that from a crystal structure of RNA polymerase II. Here, the specific nature of this cross-linking data will be discussed to assess the technical challenges and opportunities for model building. We believe that once remaining technological challenges of cross-linking/mass spectrometry have been addressed and cross linking/mass spectrometry data has been incorporated into modelling algorithms it will quickly become an indispensable companion of protein and protein complex modelling and a corner-stone of integrated structural biology. PMID- 21029780 TI - Methylphenidate enhances brain activation and deactivation responses to visual attention and working memory tasks in healthy controls. AB - Methylphenidate (MPH) is a stimulant drug that amplifies dopamineric and noradrenergic signaling in the brain, which is believed to underlie its cognition enhancing effects. However, the neurobiological effects by which MPH improves cognition are still poorly understood. Here, functional magnetic resonance imaging (fMRI) was used together with working memory (WM) and visual attention (VA) tasks to test the hypothesis that 20mg oral MPH would increase activation in the dorsal attention network (DAN) and deactivation in the default mode network (DMN) as well as improve performance during cognitive tasks in healthy men. The group of subjects that received MPH (MPH group; N=16) had higher activation than the group of subjects who received no medication (control group: N=16) in DAN regions (parietal and prefrontal cortex, regions increasingly activated with increased cognitive load) and had increased deactivation in the insula and posterior cingulate cortex (regions increasingly deactivated with increased cognitive load) and these effects did not differ for the VA and the WM tasks. These findings provide the first evidence that MPH enhances activation of the DAN whereas it alters DMN deactivation. This suggests that MPH (presumably by amplifying dopamine and noradrenergic signaling) modulates cognition in part through its effects on DAN and DMN. PMID- 21029782 TI - Fast bound pool fraction imaging of the in vivo rat brain: association with myelin content and validation in the C6 glioma model. AB - Cross-relaxation imaging (CRI) is a quantitative magnetic resonance technique that measures the kinetic parameters of magnetization transfer between protons bound to water and protons bound to macromolecules. In this study, in vivo, four parameter CRI of normal rat brains (N=5) at 3.0 T was first directly compared to histology. The bound pool fraction, f, was strongly associated with myelin density (Pearson's r=0.99, p<0.001). The correlation persisted in separate analyses of gray matter (GM; r=0.89, p=0.046) and white matter (WM; r=0.97, p=0.029). Subsequently, a new time-efficient approach for solely capturing the whole-brain parametric map of f was proposed, validated with histology, and used to estimate myelin density. Since the described approach for the rapid acquisition of f applied constraints to other CRI parameters, a theoretical analysis of error was performed. Estimates of f in normal and pathologic tissue were expected to have <10% error. A comparison of values for f obtained from the traditional four-parameter fit of CRI data versus the proposed rapid acquisition of f was within this expected margin for in vivo rat brain gliomas (N=4; mean+/ SE; 3.9+/-0.2% vs. 4.0+/-0.2%, respectively). In both whole-brain f maps and myelin density maps, replacement of normal GM and WM by proliferating and invading tumor cells could be readily identified. The rapid, whole-brain acquisition of the bound pool fraction may provide a reliable method for detection of glioma invasion in both GM and WM during animal and human imaging. PMID- 21029783 TI - A weighted-RV method to detect fine-scale functional connectivity during resting state. AB - During the resting state, in the absence of external stimuli or goal-directed mental tasks, some functionally related discrete regions of the brain show complex low-frequency fluctuations in the blood oxygenation level dependent signal. Here we developed a novel ROI-based multivariate statistical framework to obtain the fine-grained patterns of functionally specialized brain networks in the resting state. Under this framework, the weighted-RV method is proposed and used to detect the spatial fine-scale patterns of functional connectivity. This approach overcomes several major problems of the traditional resting-state data analysis methods such as Pearson correlation and linear regression analysis. By using simulation and real fMRI experiment, we have found that the weighted-RV method is shown to be more sensitive in detecting the fine-scale based low frequency connectivity even at a very low functional contrast-to-noise ratio (CNR), and this method can achieve much better performance in mapping the fine grained patterns of functionally specialized brain networks compared to the traditional methods. PMID- 21029784 TI - Spatiotemporal dynamics of electrocorticographic high gamma activity during overt and covert word repetition. AB - Language is one of the defining abilities of humans. Many studies have characterized the neural correlates of different aspects of language processing. However, the imaging techniques typically used in these studies were limited in either their temporal or spatial resolution. Electrocorticographic (ECoG) recordings from the surface of the brain combine high spatial with high temporal resolution and thus could be a valuable tool for the study of neural correlates of language function. In this study, we defined the spatiotemporal dynamics of ECoG activity during a word repetition task in nine human subjects. ECoG was recorded while each subject overtly or covertly repeated words that were presented either visually or auditorily. ECoG amplitudes in the high gamma (HG) band confidently tracked neural changes associated with stimulus presentation and with the subject's verbal response. Overt word production was primarily associated with HG changes in the superior and middle parts of temporal lobe, Wernicke's area, the supramarginal gyrus, Broca's area, premotor cortex (PMC), primary motor cortex. Covert word production was primarily associated with HG changes in superior temporal lobe and the supramarginal gyrus. Acoustic processing from both auditory stimuli as well as the subject's own voice resulted in HG power changes in superior temporal lobe and Wernicke's area. In summary, this study represents a comprehensive characterization of overt and covert speech using electrophysiological imaging with high spatial and temporal resolution. It thereby complements the findings of previous neuroimaging studies of language and thus further adds to current understanding of word processing in humans. PMID- 21029785 TI - Gray matter volume changes following reading intervention in dyslexic children. AB - Studies in children and adults with the reading disability developmental dyslexia have shown behavioral improvements after reading intervention. In another line of work, it has been shown that intensive training in a variety of cognitive and sensorimotor skills can result in changes in gray matter volume (GMV). This study examined changes in GMV following intensive reading intervention in children with dyslexia using voxel-based morphometry (VBM). Eleven dyslexic children underwent an eight week training focused on mental imagery, articulation and tracing of letters, groups of letters and words, which resulted in significant gains in reading skills. This was followed by an eight week null period (control) where no intervention was administered and no further significant gains in reading were observed. Structural scans were obtained before the intervention, after the intervention and after the null period. GMV increases between the first two time points were found in the left anterior fusiform gyrus/hippocampus, left precuneus, right hippocampus and right anterior cerebellum. However these areas did not change between time points two and three (control period), suggesting that the changes were specific to the intervention period. These results demonstrate for the first time that (1) training-induced changes in GMV can be observed in a pediatric sample and (2) reading improvements induced by intervention are accompanied by GMV changes. PMID- 21029786 TI - Exploring the molecular phylogeny of phasmids with whole mitochondrial genome sequences. AB - Phasmids are remarkable mimics of twigs, sticks, and leaves. This extreme adaptation for crypsis can easily lead to the convergent evolution of morphology, making it difficult to establish a taxonomic system of phasmids. Accordingly, there are multiple phylogenetic hypotheses that conflict with each other. Phylogenetic arrangements suggested by molecular data disagree with the morphology-based taxonomy in some instances. We collected 13 phasmatodean species, sequenced their mitochondrial genomes, and recovered their molecular phylogeny. Our analyses did not support the monophyly of Areolatae or Anareolatae, two major infraorders of Phasmatodea. The position of Neohirasea was also quite different from the conventional taxonomic systems, thus challenging the previously assumed monophyly of the subfamily Lonchodinae. The enigmatic taxon, Timema, was shown to be distantly related to other phasmatodeans. PMID- 21029788 TI - Increased risk for malignant neoplasms among patients with cirrhosis. AB - BACKGROUND & AIMS: It is not clear how cirrhosis affects the risks for hepatocellular carcinoma (HCC) and non-HCC cancers, which are rare among these patients. We assessed the risk for malignant neoplasms in patients with cirrhosis. METHODS: Patients diagnosed with cirrhosis in Gothenburg, Sweden, from 1994 to 2005 were identified and linked to the National Cancer and Death registers. We studied data from 1019 patients with cirrhosis: 68% men, 48% with alcoholic liver disease (ALD), 10% with hepatitis C virus (HCV), and 12% with HCV + ALD. Standardized incidence ratios for malignant neoplasms were calculated (corrected for sex, age, and calendar year according to data from the general Swedish population). The follow-up period was 3290 person-years. RESULTS: Overall, 114 (11%) patients developed HCC; HCC occurred more frequently among patients with HCV than other diseases (P < .05). HCC risk did not differ among patients with HCV, with or without ALD (P > .05). Compared with the general population, cirrhotic patients had increased risk for HCC (26-fold); cholangiocarcinoma (13-fold); and esophageal (8-fold), pancreatic (5-fold), and colorectal and lung cancers (each 4-fold). The risk for cholangiocarcinoma increased mainly among patients with non-ALD cirrhosis, whereas the risk for extrahepatic malignancies increased mainly among patients with ALD and cirrhosis. CONCLUSIONS: The overall risk for non-HCC malignancies is more than 2-fold greater for patients with cirrhosis (mostly in biliary and gastrointestinal malignancies) than of the general population. The risk for non-HCC cancers differs between patients with ALD and non-ALD cirrhosis. The increased risk for HCC among patients with cirrhosis is associated with HCV; it is the same among patients with HCV, with or without ALD. PMID- 21029787 TI - Alcohol and smoking as risk factors in an epidemiology study of patients with chronic pancreatitis. AB - BACKGROUND & AIMS: Alcohol has been implicated in the development of chronic pancreatitis (CP) in 60%-90% of patients, although percentages in the United States are unknown. We investigated the epidemiology of alcohol-related CP at tertiary US referral centers. METHODS: We studied data from CP patients (n = 539) and controls (n = 695) enrolled in the North American Pancreatitis Study-2 from 2000 to 2006 at 20 US referral centers. CP was defined by definitive evidence from imaging or histologic analyses. Subjects and physicians each completed a study questionnaire. Using physician-assigned diagnoses, patients were assigned to an etiology group: alcohol (with/without other diagnoses), nonalcohol (any etiology of CP from other than alcohol), or idiopathic (no etiology identified). RESULTS: The distribution of patients among etiology groups was: alcohol (44.5%), nonalcohol (26.9%), and idiopathic (28.6%). Physicians identified alcohol as the etiology more frequently in men (59.4% men vs 28.1% women), but nonalcohol (18% men vs 36.7% women) and idiopathic etiologies (22.6% men vs 35.2% women) more often in women (P < .01 for all comparisons). Nonalcohol etiologies were equally divided among obstructive, genetic, and other causes. Compared with controls, patients with idiopathic CP were more likely to have ever smoked (58.6% vs 49.7%, P < .05) or have a history of chronic renal disease or failure (5.2% vs 1.2%, P < .01). In multivariate analyses, smoking (ever, current, and amount) was independently associated with idiopathic CP. CONCLUSIONS: The frequency of alcohol-related CP at tertiary US referral centers is lower than expected. Idiopathic CP and nonalcohol etiologies represent a large subgroup, particularly among women. Smoking is an independent risk factor for idiopathic CP. PMID- 21029789 TI - Immunosuppressive therapy allows recovery from liver failure in children with autoimmune hepatitis. AB - BACKGROUND & AIMS: Patients with autoimmune hepatitis (AIH) frequently have liver failure (LF) at the time of diagnosis; their response to immunosuppressive therapy has not been thoroughly analyzed. We evaluated the outcomes of children with AIH and LF who received immunosuppressive therapy and analyzed predictors of liver function recovery. METHODS: We collected data from 237 children that had AIH between September 1996 and December 2008; 50 had LF (defined as prothrombin time <50%) and had not received prior treatment. Patients were treated with either 2 mg/kg/day prednisone at doses up to 60 mg/day (n = 13) or 1 mg/kg/day prednisone at doses up to 40 mg/day plus cyclosporine at blood levels of 200 +/- 50 ng/mL (n = 37). RESULTS: Of the 50 patients studied, 45 (90%) achieved prothrombin time >50% in a median time of 24 days (range of 4-257 days); 93% of these patients achieved this within the first 90 days of treatment. Two of the 45 patients who responded to immunosuppression required liver transplantation because of complications related to portal hypertension, and 3 died because of infection. Three of the 5 nonresponders received liver transplants - 1 remained on the waiting list, and the other died because of central nervous system bleeding. Infection was the only independently associated significant factor that delayed recovery from LF (odds ratio = 7.7, 95% confidence interval, 1.5-40). Each therapeutic approach had similar efficacy. CONCLUSIONS: Most pediatric patients with AIH recover after LF with immunosuppressive therapy; liver transplantation could be avoided or delayed. Infection was the most frequent cause of morbidity and mortality in these patients. PMID- 21029791 TI - Diet improves perception of health and well-being in symptomatic, but not asymptomatic, patients with celiac disease. AB - BACKGROUND & AIMS: The benefits of serologic screening and early diagnosis of celiac disease in asymptomatic patients are not known. We investigated the impact of a gluten-free diet on self-perceived health and well-being in symptomatic and asymptomatic patients with celiac disease. METHODS: We performed a prospective study of 698 consecutive adults newly diagnosed with celiac disease because of classic (n = 490) or extraintestinal (n = 62) symptoms or through screening of at risk groups (n = 146; 23 were asymptomatic and analyzed separately). The survey included questions on health and well-being; quality of life was evaluated by the psychological general well-being (PGWB) questionnaire. Patients were followed for 1 year of treatment; 110 healthy subjects served as controls. RESULTS: On a gluten-free diet, self-perceived health improved significantly among patients with classic symptoms and those detected by screening. Patients in all groups were equally concerned about their health before the diagnosis, but anxiety was alleviated by the gluten-free diet. At diagnosis, the quality of life reduced among all 3 groups but improved significantly among patients on the diet. Among the 23 asymptomatic patients, perception of health worsened and concern about health increased while they were on the diet. CONCLUSIONS: Self-perceived health and well-being were low among patients at the time they were diagnosed with celiac disease. Most patients benefited from a gluten-free diet, so it is important to identify patients with celiac disease. Perception of health decreased among asymptomatic cases, which discourages population-based screening. PMID- 21029790 TI - Cigarette smoking and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition study. AB - BACKGROUND & AIMS: There has been consistent evidence for a relationship between smoking and colorectal cancer (CRC), although it is not clear whether the colon or rectum is more sensitive to the effects of smoking. We investigated the relationships between cigarette smoking and risk of CRC and tumor location. METHODS: We analyzed data from 465,879 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) study; 2741 developed CRC during the follow-up period (mean, 8.7 years). Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: The risk of colon carcinoma was increased among ever smokers (HR, 1.18; 95% CI, 1.06-1.32) and former cigarette smokers (HR, 1.21; 95% CI, 1.08-1.36), compared with never smokers; the increased risk for current smokers was of borderline significance (HR, 1.13; 95% CI, 0.98-1.31). When stratified for tumor location, the risk of proximal colon cancer was increased for former (HR, 1.25; 95% CI, 1.04-1.50) and current smokers (HR, 1.31; 95% CI, 1.06-1.64), but the risks for cancers in the distal colon or rectum were not. Subsite analyses showed a nonsignificant difference between the proximal and distal colon (P = .45) for former smokers and a significant difference for current smokers (P = .02). For smokers who had stopped smoking for at least 20 years, the risk of developing colon cancer was similar to that of never smokers. CONCLUSIONS: Ever smokers have an increased risk of colon cancer, which appeared to be more pronounced in the proximal than the distal colon location. PMID- 21029792 TI - Identification and lineage genotyping of South American trypanosomes using fluorescent fragment length barcoding. AB - Trypanosoma cruzi and Trypanosoma rangeli are human-infective blood parasites, largely restricted to Central and South America. They also infect a wide range of wild and domestic mammals and are transmitted by a numerous species of triatomine bugs. There are significant overlaps in the host and geographical ranges of both species. The two species consist of a number of distinct phylogenetic lineages. A range of PCR-based techniques have been developed to differentiate between these species and to assign their isolates into lineages. However, the existence of at least six and five lineages within T. cruzi and T. rangeli, respectively, makes identification of the full range of isolates difficult and time consuming. Here we have applied fluorescent fragment length barcoding (FFLB) to the problem of identifying and genotyping T. cruzi, T. rangeli and other South American trypanosomes. This technique discriminates species on the basis of length polymorphism of regions of the rDNA locus. FFLB was able to differentiate many trypanosome species known from South American mammals: T. cruzi cruzi, T. cruzi marinkellei, T. dionisii-like, T. evansi, T. lewisi, T. rangeli, T. theileri and T. vivax. Furthermore, all five T. rangeli lineages and many T. cruzi lineages could be identified, except the hybrid lineages TcV and TcVI that could not be distinguished from lineages III and II respectively. This method also allowed identification of mixed infections of T. cruzi and T. rangeli lineages in naturally infected triatomine bugs. The ability of FFLB to genotype multiple lineages of T. cruzi and T. rangeli together with other trypanosome species, using the same primer sets is an advantage over other currently available techniques. Overall, these results demonstrate that FFLB is a useful method for species diagnosis, genotyping and understanding the epidemiology of American trypanosomes. PMID- 21029793 TI - Facile formation of dynamic hydrogel microspheres for triggered growth factor delivery. AB - Dynamic hydrogels have emerged as an important class of biomaterials for temporal control over growth factor delivery. In this study we formed dynamic hydrogel microspheres from protein-polymer conjugates using an aqueous two-phase suspension polymerization process. This polymerization process enabled rapid microsphere formation without the use of an organic phase, surfactants, mechanical strain or toxic radical initiators. The microspheres' size distribution was modulated by varying the protein-polymer conformation in the pre polymer solution. Notably, the protein's ligand-induced, nanometer-scale conformational change translated to maximum hydrogel volume changes of 76+/-10%. The magnitude of the microspheres' volume change was tuned by varying the crosslinking time and ligand identity. After characterizing the microspheres' dynamic properties, we encapsulated two important therapeutic proteins, vascular endothelial growth factor (VEGF) and bone morphogenetic protein-2 (BMP-2), in the hydrogel microspheres and characterized how the microspheres' dynamic properties controlled their release. Significantly, the aqueous two-phase suspension polymerization process enabled high encapsulation efficiencies (65.8+/-4.8% and 79.5+/-3.0% for VEGF and BMP-2, respectively). Also, the microspheres' ligand induced volume change triggered VEGF and BMP-2 release at specific, predetermined times. There are hundreds of proteins that undergo well-characterized conformational changes that could be processed into hydrogel microspheres via aqueous two-phase suspension polymerizations. Therefore, this approach could be used to form dynamic, growth-factor-releasing hydrogel microspheres that respond to a broad range of specific biochemical ligands. PMID- 21029795 TI - Pre-operative stenting is associated with a higher prevalence of post-operative complications following pancreatoduodenectomy. AB - OBJECTIVES: Whilst there are theoretical benefits from pre-operatively draining the biliary tree prior to pancreatoduodenectomy (PD), the current literature does not support this intervention. The aim of this study was to explore the relationship between pre-operative stenting, bactibilia and outcome in a large United Kingdom tertiary referral practice. METHODS: Patients undergoing PD were identified from a prospectively maintained database. The presence or absence of a stent prior to PD, and the results of bile cultures taken at PD were related to the subsequent post-operative course and the development of complications. RESULTS: 280 patients underwent PD for periampullary malignancies, all of whom presented with jaundice. 118 patients were stented prior to referral (98 ERCP, 20 PTC). Bile cultures were positive more frequently in the stent group (83% vs. 55%; p = 0.000002) and bactibilia was more common after ERCP than PTC (83% vs. 56%; p = 0.006). The overall prevalence of complications was 54% in the stented and 41% in the non-stented group (p = 0.03) with statistical significance achieved for pancreatic leak (p = 0.013) and haemorrhagic complications (p = 0.03). Comparing stent with no stent, there as no difference in the 30-day mortalities (8.5% vs. 6.8%; p = 0.6) or the 1-year mortality rates (35% vs. 28%; p = 0.21). Mortality rates in the infection versus no infection groups were comparable at 30 days (8.5% vs. 5.5%; p = 0.21), and at 1 year (30.7% vs. 26.4%; p = 0.25). CONCLUSIONS: Pre-operative stent insertion prior to PD is associated with increased morbidity but not mortality and this is greatest for stents placed at ERCP. PMID- 21029794 TI - Key role of alkaline phosphatase in the development of human-derived nanoparticles in vitro. AB - Alkaline phosphatase (ALP) is an enzyme critical for physiological and pathological biomineralization. Experiments were designed to determine whether ALP participates in the formation of calcifying nanometer sized particles (NPs) in vitro. Filtered homogenates of human calcified carotid artery, aorta and kidney stones were inoculated into cell culture medium containing 10% fetal bovine serum in the absence or presence of inhibitors of ALP or pyrophosphate. A calcific NP biofilm developed within 1 week after inoculation and their development was reduced by pyrophosphate and inhibitors of ALP. ALP protein and enzymatic activity were detected in washed NPs, whether calcified or decalcified. Therefore, ALP activity is required for the formation of calcifying NPs in vitro, as has previously been implicated during pathological calcification in vivo. PMID- 21029796 TI - Single-incision laparoscopic-assisted surgery for colon cancer via a periumbilical approach using a surgical glove: initial experience with 9 cases. AB - Our initial experience of performing a single-incision laparoscopic-assisted (SILS) colectomy using a "home-made" multichannel port system is presented. Nine patients (5 women) with a median age of 67 years (range, 55-72 years) and a median body mass index of 21.2 kg/m(2) (range, 17.8-26.7 kg/m(2)) underwent the SILS colectomy for colon cancer between September 2009 and March 2010. The sites of the primary tumor were the ascending colon (n=2), hepatic flexure (n=1), transverse colon (n=2), and sigmoid colon (n=4). Each trocar was introduced intraperitoneally through each finger of a surgical glove attached to the wound protector, which was applied to a midline fasciotomy made via a 3/4-circular periumbilical incision. If necessary, one to three radial splits were added to the incision. The colon was mobilized intracorporeally, and the vessels were ligated intra- or extracorporeally. All the patients underwent a curative segmental colectomy without conversion to a standard multiport laparoscopy or open surgery. The median operative time and blood loss were 140 min (range, 135 165 min) and 50 mL (range, 20-225 mL), respectively. The median number of harvested lymph nodes was 18 (range, 6-31). The pathological stages included stage 0 (n=2), stage I (n=6), and stage III (n=1). The median number of postoperative analgesic use was one (range, 0-6). No intra- or postoperative complications occurred in this series. Our SILS colectomy procedure seems feasible and safe in selected patients with colon cancer. PMID- 21029797 TI - Primary subcutaneous hydatid cysts: a review of 22 cases. AB - AIM: We aimed to review cases of primary subcutaneous hydatid cysts whether this is a fearsome disease or a benign progressed pathology. These cysts are rare, have difficulty in diagnosis and management, particularly for inexperienced clinicians. METHODS: We searched key words of "echinococcosis, hydatid, soft tissue, subcutaneous, cutaneous" at MEDLINE/PUBMED. We eliminated unrelated articles, cases with primary visceral hydatid focus or muscular cysts. Twenty publications including 22 patients were suitable for analysis. We contacted with authors of the articles for missing data. Follow-up periods and recurrences were updated. RESULTS: All patients were from endemic areas and most from rural regions (90%). Most frequent locations were thigh (27%) and gluteal region (9%). Mean size was 5.7 + 3.1 cm (2-15 cm). Main symptom (70%) was painless, slow growing mass with normal overlying skin. Serologic tests were usually negative (79%). Only 45% of the patients were diagnosed as hydatid cyst before treatment. Most cases (91%) were treated by surgical excision and spillage occurred at 25% of them. Cyst pouchs were irrigated with protoscolocidal solutions after cyst removal. There was no anaphylaxis during procedures. There was no recurrence with a mean follow-up of 26 + 18 months (6-60 months). CONCLUSION: Primary subcutaneous hydatid cyst should be in mind for differential diagnosis of soft tissue masses particularly for patients who lived in regions where hydatid cyst is endemic. There is no reported anaphylaxis or recurrence during diagnostic or therapeutic interventions. Complete excision is the best treatment option. Primary subcutaneous hydatid cysts generally look like a benign progressed disease. PMID- 21029798 TI - A rare complication of hiatal hernia. PMID- 21029799 TI - Morphogens and the parietal cell: shaping up acid secretion. PMID- 21029801 TI - Helicobacter pylori and esophageal disease: wake-up call? PMID- 21029802 TI - Genetics and environmental interactions shape the intestinal microbiome to promote inflammatory bowel disease versus mucosal homeostasis. PMID- 21029803 TI - Unusual cause of a common presentation. PMID- 21029804 TI - A patient with ulcerative colitis and an unusual rash. PMID- 21029805 TI - An unusual retroperitoneal tumor in a young woman. PMID- 21029806 TI - Immune responses against a liver-stage malaria antigen induced by simian adenoviral vector AdCh63 and MVA prime-boost immunisation in non-human primates. AB - Malaria is a major health problem as nearly half of the human population is exposed to this parasite causing around 600 million clinical cases annually. Prime-boost regimes using simian adenoviral vectors and MVA expressing the clinically relevant Plasmodium falciparum ME.TRAP antigen have shown outstanding protective efficacy in mouse models. We now extend those observations to macaque monkeys. Immunisation with AdCh63 elicited a median response of 869 IFN-gamma SFC/million PBMCs to ME.TRAP and responses were boosted by MVA to reach 5256 SFC/million PBMCs, increasing at the same time the breadth of the T cell responses to cover the complete ME.TRAP antigen. Intramuscular vaccination was more immunogenic than the intradermal route, and MVA could be used repeatedly for up to 3 times to boost adenovirus-primed responses. An interval of 16 weeks between repeated MVA injections was optimal to enhance cytokine production by T cells and improve the CD8 multifunctional responses. Antibodies to TRAP were exceptionally high and maintained for a long period of time after the prime-boost regime. These results in non-human primates highlight the potential of this vaccination regime and encourage its future use in clinical trials. PMID- 21029807 TI - Serotype specific invasive capacity and persistent reduction in invasive pneumococcal disease. AB - Defining the propensity of Streptococcus pneumoniae (SP) serotypes to invade sterile body sites following nasopharyngeal (NP) acquisition has the potential to inform about how much invasive pneumococcal disease (IPD) may occur in a typical population with a given distribution of carriage serotypes. Data from enhanced surveillance for IPD in Massachusetts children <=7 years in 2003/04, 2006/07 and 2008/09 seasons and surveillance of SP NP carriage during the corresponding respiratory seasons in 16 Massachusetts communities in 2003/04 and 8 of the 16 communities in both 2006/07 and 2008/09 were used to compute a serotype specific "invasive capacity (IC)" by dividing the incidence of IPD due to serotype x by the carriage prevalence of that same serotype in children of the same age. A total of 206 IPD and 806 NP isolates of SP were collected during the study period. An approximate 50-fold variation in the point estimates between the serotypes having the highest (18C, 33F, 7F, 19A, 3 and 22F) and lowest (6C, 23A, 35F, 11A, 35B, 19F, 15A, and 15BC) IC was observed. Point estimates of IC for most of the common serotypes currently colonizing children in Massachusetts were low and likely explain the continued reduction in IPD from the pre-PCV era in the absence of specific protection against these serotypes. Invasive capacity differs among serotypes and as new pneumococcal conjugate vaccines are introduced, ongoing surveillance will be essential to monitor whether serotypes with high invasive capacity emerge (e.g. 33F, 22F) as successful colonizers resulting in increased IPD incidence due to replacement serotypes. PMID- 21029808 TI - Multivalent DNA vaccine induces protective immune responses and enhanced resistance against Cryptosporidium parvum infection. AB - The aim of this work was to evaluate efficiency as well as the type of immune response, Th1 or Th2, induced by multivalent DNA vaccinations in C57BL/6 interleukin-12p40 (IL-12p40) knockout (KO) mice. A recombinant pVAX-15-23 plasmid DNA was constructed by inserting surface glycoprotein (cp15- and p23)-encoding DNA into the pVAX1 expression vector. Various parameters including antibody and cytokine responses, proliferation assay and oocyst shedding were used to evaluate the type of immune response and the level of protection against challenge infection. Obtained results indicated that plasmid pVAX-15-23 induced strong protective immune response against C. parvum characterized by dominance of IgG2a, high level of INF-gamma and lower level of the oocysts shedding after challenge infection. Moreover, co-immunization with the multivalent DNA and pMEM12R plasmid encoding IL-12 can further enhance these responses compared with the multivalent DNA alone. The obtained results suggest that multivalent pVAX-15-23 DNA vaccine may be a candidate as a generic approach to C. parvum immunization applicable to clinical practice. PMID- 21029809 TI - Economic analysis of the global polio eradication initiative. AB - The global polio eradication initiative (GPEI), which started in 1988, represents the single largest, internationally coordinated public health project to date. Completion remains within reach, with type 2 wild polioviruses apparently eradicated since 1999 and fewer than 2000 annual paralytic poliomyelitis cases of wild types 1 and 3 reported since then. This economic analysis of the GPEI reflects the status of the program as of February 2010, including full consideration of post-eradication policies. For the GPEI intervention, we consider the actual pre-eradication experience to date followed by two distinct potential future post-eradication vaccination policies. We estimate GPEI costs based on actual and projected expenditures and poliomyelitis incidence using reported numbers corrected for underreporting and model projections. For the comparator, which assumes only routine vaccination for polio historically and into the future (i.e., no GPEI), we estimate poliomyelitis incidence using a dynamic infection transmission model and costs based on numbers of vaccinated children. Cost-effectiveness ratios for the GPEI vs. only routine vaccination qualify as highly cost-effective based on standard criteria. We estimate incremental net benefits of the GPEI between 1988 and 2035 of approximately 40-50 billion dollars (2008 US dollars; 1988 net present values). Despite the high costs of achieving eradication in low-income countries, low-income countries account for approximately 85% of the total net benefits generated by the GPEI in the base case analysis. The total economic costs saved per prevented paralytic poliomyelitis case drive the incremental net benefits, which become positive even if we estimate the loss in productivity as a result of disability as below the recommended value of one year in average per-capita gross national income per disability-adjusted life year saved. Sensitivity analysis suggests that the finding of positive net benefits of the GPEI remains robust over a wide range of assumptions, and that consideration of the additional net benefits of externalities that occurred during polio campaigns to date, such as the mortality reduction associated with delivery of Vitamin A supplements, significantly increases the net benefits. This study finds a strong economic justification for the GPEI despite the rising costs of the initiative. PMID- 21029812 TI - Frequency of left ventricular thrombus in patients with anterior wall acute myocardial infarction treated with percutaneous coronary intervention and dual antiplatelet therapy. AB - The aim of the present study was to investigate the prevalence of left ventricular (LV) thrombus formation and important determinants in patients with acute ST elevation myocardial infarction localized to the anterior wall treated with percutaneous coronary intervention (PCI) and dual-antiplatelet therapy. One hundred selected patients with ST elevation myocardial infarctions revascularized with PCI in the left anterior descending coronary artery were included. The patients participated in the Autologous Stem Cell Transplantation in Acute Myocardial Infarction (ASTAMI) trial. All were treated with aspirin 75 mg/day and clopidogrel 75 mg/day and underwent serial echocardiography and magnetic resonance imaging during the first 3 months after PCI. After 4 to 5 days, the ejection fraction and infarct size in percentage of the left anterior descending coronary artery area were assessed using single photon-emission computed tomography in addition to the ejection fraction by echocardiography. LV thrombi were detected in 15 patients during the first 3 months, 2/3 of them within the first week. No differences in baseline characteristics between the groups with and without LV thrombi were shown. However, in the thrombus group, significantly higher peak creatine kinase levels (6,128 vs 2,197 U/L, p <0.01), larger infarct sizes (82.5% vs 63.8%, p <0.01), and lower ejection fractions on single photon emission computed tomography (35.5% vs 40.0%, p = 0.03) and on echocardiography (43.0% vs 46.0%, p = 0.03) were found compared to patients without LV thrombi. In conclusion, LV thrombus formation is a frequent finding in patients with anterior wall ST elevation myocardial infarction treated acutely with PCI and dual antiplatelet therapy and should be assessed by echocardiography within the first week. PMID- 21029814 TI - Comparison of 600 versus 300-mg Clopidogrel loading dose in patients with ST segment elevation myocardial infarction undergoing primary coronary angioplasty. AB - The aim of the present study was to compare 600- and 300-mg clopidogrel loading doses in patients with ST-segment elevation myocardial infarctions who underwent primary percutaneous coronary intervention (PCI). Two hundred fifty-five consecutive patients presenting with ST-segment elevation myocardial infarctions who underwent primary PCI were enrolled. Patients were divided into 2 groups on the basis of the loading dose of clopidogrel received before the procedure (600 vs 300 mg). Procedural angiographic end points and 1-year major adverse cardiac events were compared between the 2 groups. Major adverse cardiac events were defined as death, nonfatal myocardial infarction, and target vessel revascularization. There were no significant differences in baseline clinical and angiographic features between the 2 groups: 157 (62%) in the clopidogrel 600 mg group and 98 (38%) in the 300 mg group. Patients receiving 600-mg loading dose of clopidogrel showed a significantly lower incidence of post-PCI myocardial blush grade 0 or 1 (odds ratio 0.64, 95% confidence interval 0.43 to 0.96, p = 0.03) and significantly less common no-reflow phenomenon (odds ratio 0.38, 95% confidence interval 0.15 to 0.98, p = 0.04) compared to those in the 300-mg group. Propensity-adjusted Cox analysis showed significantly higher survival free of major adverse cardiac events in patients receiving 600-mg loading dose of clopidogrel compared to those receiving the lower dose (hazard ratio 0.57, 95% confidence interval 0.33 to 0.98, p = 0.04). In conclusion, a 600-mg loading dose of clopidogrel is associated with improvements in procedural angiographic end points and 1-year clinical outcomes in patients with ST-segment elevation myocardial infarction who undergo primary PCI compared to a 300-mg dose. PMID- 21029813 TI - Comparison of outcomes in patients with insulin-dependent versus non-insulin dependent diabetes mellitus receiving drug-eluting stents (from the first phase of the prospective multicenter German DES.DE registry). AB - Drug-eluting stents have been effective in randomized controlled trials, but their safety and efficacy in patients with insulin-dependent diabetes has not been well studied. Baseline clinical and angiographic characteristics and in hospital and follow-up events were recorded for enrolled patients. From October 2005 and October 2006, 581 patients with insulin-dependent diabetes and 1,078 with non-insulin-dependent diabetes treated with sirolimus- and paclitaxel eluting stents were enrolled at 98 sites. The composite of death, myocardial infarction, and stroke, defined as major adverse cardiac and cerebrovascular events, as well as target vessel revascularization was used as the primary end point. Multiple logistic regression analysis was used to adjust for confounding parameters. Baseline clinical characteristics were more severe in patients with insulin-dependent diabetes, whereas descriptive characteristics were not unique. At 1-year follow-up, the comparison between the 2 groups revealed significantly higher rates of overall death (7.4% vs 4.6%, p <0.05), target vessel revascularization (15.1% vs 10.4%, p <0.05), and overall stent thrombosis (6.5% vs 4.1%, p <0.05) for insulin-dependent patients, while rates of major adverse cardiac and cerebrovascular events were not significantly different (12.8% vs 9.9%, p = 0.09). These results persisted even after risk adjustment for heterogenous baseline characteristics of the 2 groups. In conclusion, the data generated from the German Drug-Eluting Stent (DES.DE) registry revealed that even with drug-eluting stents, the annual risk for death, target vessel revascularization, and thrombotic events remains higher in patients with insulin dependent diabetes compared to those with non-insulin-dependent diabetes. PMID- 21029815 TI - Peak cardiac troponin-T level, scintigraphic myocardial infarct size and one-year prognosis in patients undergoing primary percutaneous coronary intervention for acute myocardial infarction. AB - Current guidelines recommend troponin T (TnT) as the biomarker of choice in the diagnosis of myocardial infarction. In patients with ST-elevation myocardial infarction (STEMI) however, its role in providing a measurement of infarct size and its association with survival is less well established. We sought to assess the correlation of TnT and creatine kinase-MB (CK-MB) with scintigraphically determined infarct size and to assess the predictive value of all 3 parameters on 12-month mortality. Patients presenting with STEMI managed with primary percutaneous intervention underwent serial TnT and CK-MB measurements at admission and for >=72 hours after presentation. Before hospital discharge patients underwent assessment of infarct size by technetium-99m sestamibi single photon emission computed tomographic (SPECT) scan. Clinical follow-up was performed up to 1 year. Data were available for 1,237 patients. Mean age was 62.9 +/- 12.9 years. Infarct location was anterior in 509 patients (41%); 75 (6.1%) had cardiogenic shock. Median admission and peak TnT were 0.74 MUg/L (0.10 to 2.70) and 3.70 MUg/L (1.69 to 6.99), respectively. Corresponding values for CK-MB were 44.1 U/L (21.0 to 108.8) and 160.0 U/L (69.0 to 301.0), respectively. Median infarct size on SPECT scan was 12.0% (3.0 to 25.0) of the left ventricle. Peak TnT and CK-MB demonstrated similar moderate correlation with final infarct size (r = 0.45, p <0.001, and r = 0.41, p <0.001 respectively). This correlation was not affected by Thrombolysis In Myocardial Infarction flow grade after intervention. At 1 year, 47 patients (3.8%) had died. Final infarct size at SPECT scanning better predicted mortality than peak TnT or CK-MB. In conclusion, this study is the largest investigation on the value of cardiac troponin for assessment of infarct size in acute STEMI. Compared to peak CK-MB, peak TnT shows similar correlation with scintigraphic infarct size, although scintigraphic infarct size remains a better correlate of 1-year mortality than either biomarker. PMID- 21029816 TI - Impact of transfer for primary percutaneous coronary intervention on survival and clinical outcomes (from the HORIZONS-AMI Trial). AB - Primary percutaneous coronary intervention (PCI) is the preferred reperfusion strategy in patients with ST-segment elevation myocardial infarction (STEMI). We evaluated whether presentation of patients with STEMI to a noninterventional facility requiring transfer for primary PCI compared to direct admission to a PCI center has an impact on clinical outcomes. Of 3,602 patients enrolled in the multicenter, prospective HORIZONS-AMI trial, 988 (24.7%) were transferred for primary PCI and 2,614 were directly admitted to an interventional hospital. Clinical outcomes at 30 days and 1 year were evaluated. Median time to reperfusion in patients with transfer was 67 minutes longer compared to patients without transfer (272 vs 205 minutes, p <0.001), and first door-to-balloon time was 47 minutes longer (134 vs 87 minutes, p <0.001). At 30 days and 1 year there were no significant differences between patients with and without transfer in the rates of major adverse cardiac events (30 days 5.8% vs 5.4%, p = 0.68; 1 year 11.6% vs 12.0%, p = 0.74), major bleeding (30 days 7.3% vs 6.9%, p = 0.66; 1 year 7.9% vs 7.4%, p = 0.63), or mortality (30 days 2.6% vs 2.6%, p = 0.92; 1 year 4.0% vs 4.2%, p = 0.81). In transfer and nontransfer patients use of bivalirudin compared to unfractionated heparin plus glycoprotein IIb/IIIa inhibitor was associated with lower rates of bleeding, cardiac death, and net adverse clinical events. In conclusion, in the HORIZONS-AMI trial, 30-day and 1-year survival rates and clinical outcomes were comparable in patients with STEMI requiring and not requiring transfer for primary PCI. PMID- 21029817 TI - Lack of effect of oral beta-blocker therapy at discharge on long-term clinical outcomes of ST-segment elevation acute myocardial infarction after primary percutaneous coronary intervention. AB - Beta-blocker therapy is recommended after ST-segment elevation acute myocardial infarction (STEMI) in current guidelines, although its efficacy in those patients who have undergone primary percutaneous coronary intervention (PCI) has not been adequately evaluated. Of 12,824 consecutive patients who underwent sirolimus eluting stent implantation in the J-Cypher registry, we identified 910 patients who underwent PCI within 24 hours from onset of STEMI. Three-year outcomes were evaluated according to use of beta blockers at hospital discharge (349 patients in beta-blocker group and 561 patients in no-beta-blocker group). Patients in the beta-blocker group more frequently had hypertension, low left ventricular ejection fraction (LVEF), a left anterior descending artery infarct, and statin use than those in the no-beta-blocker group. No difference was observed between the beta-blocker and no-beta-blocker groups in mortality (6.6% vs 6.6%, p = 0.85; propensity score adjusted hazard ratio 1.10, 95% confidence interval 0.64 to 1.90, p = 0.70) or in incidence of major adverse cardiac events (all-cause death, recurrent myocardial infarction, and heart failure hospitalization, 13.5% vs 12.1%, p = 0.91; hazard ratio 1.13, 95% confidence interval 0.76 to 1.66, p = 0.53). Better outcomes were observed in the beta-blocker group than in the no beta-blocker group in a subgroup of patients with LVEF <=40% (n = 125, death 6.4% vs 17.4%, p = 0.04; major adverse cardiac events 14.5% vs 31.8%, p = 0.009). In conclusion, beta-blocker therapy was not associated with better 3-year clinical outcomes in patients with STEMI who underwent primary PCI and had preserved LVEF. PMID- 21029818 TI - Validation of long-term benefits of bivalirudin versus unfractionated heparin in routine clinical practice after percutaneous coronary intervention. AB - Randomized controlled trials have shown improved short-term bleeding outcomes for bivalirudin compared to unfractionated heparin (UFH) in patients undergoing percutaneous coronary intervention (PCI) for stable angina and acute coronary syndrome. This study analyzed the impact of bivalirudin-based anticoagulation strategy versus UFH-based anticoagulation strategy on long-term bleeding complications and major adverse cardiac events in patients undergoing PCI in routine clinical practice. From September 2005 to April 2009, 3,367 consecutive patients who underwent PCI for stable angina or non-ST-segment elevation acute coronary syndrome at Brigham and Women's Hospital were studied. Of these patients, 2,228 patients (66%) received UFH and 1,139 (34%) received bivalirudin. Bleeding complication and major adverse cardiac event rates were compared at discharge, 30 days, and 1 year. In a propensity-score matched analysis, bivalirudin-based anticoagulation strategy was associated with lower bleeding complications at 30 days (7.0% vs 13.7%, p = 0.001) and 1 year (12.7% vs 18.9%, p = 0.013). Major adverse cardiac event rates were not significantly different between groups at discharge, 30 days, and 1 year (6.4% vs 8.3%, p = 0.103; 9.4% vs 10.9%, p = 0.449; 12.1% vs 14.8%, p = 0.235, respectively). There was no difference in all-cause mortality rates between the 2 groups (0.9% vs 0.8%, p = 0.808, at discharge; 1.9% vs 3.6%, p = 0.112, at 30 days; 3.6% vs 5.5%, p = 0.195, at 1 year). In conclusion, in a real-world cohort of patients undergoing PCI, bivalirudin-based anticoagulation strategy is associated with a significant decrease in risk of bleeding complications after 30 days and 1 year compared to a UFH-based anticoagulation strategy with no increase in risk for major adverse cardiac events. PMID- 21029819 TI - Impact of baseline plaque components on plaque progression in nonintervened coronary segments in patients with angina pectoris on rosuvastatin 10 mg/day. AB - It is not well known which lesions are progressed or regressed in patients with angina pectoris who use statins. We assessed the impact of plaque components on plaque progression in patients with angina pectoris who used rosuvastatin 10 mg/day using virtual histology plus intravascular ultrasound. Sixty-six patients who underwent baseline and 9-month follow-up virtual histology plus intravascular ultrasound for nonintervened intermediate coronary stenosis were grouped according to plaque progression (increase of plaque plus media area, n = 22) or plaque regression (decrease of plaque plus media area, n = 44) at baseline minimum lumen area (MLA) site at follow-up and compared the various parameters including baseline plaque components between the 2 groups. Follow-up low-density lipoprotein cholesterol was not significantly different between the progression and regression groups (85 +/- 30 vs 82 +/- 24 mg/dl, p = 0.6). Baseline percent necrotic core (NC) area was significantly larger (26.1 +/- 10.9% vs 17.6 +/- 10.8%, p = 0.004) and baseline percent fibrofatty area was significantly smaller (8.1 +/- 6.2% vs 14.2 +/- 12.1%, p = 0.008) at the MLA site in the progression group compared to the regression group. Thin-cap fibroatheroma was observed more frequently in the progression group compared to the regression group (32% vs 9%, p = 0.020). Change of plaque plus media area from baseline to follow-up at the MLA site correlated with baseline percent NC area (r = 0.375, p = 0.002), baseline percent fibrofatty area (r = -0.388, p = 0.001), and baseline percent fibrotic area (r = -0.242, p = 0.050). Baseline percent NC area at the MLA site was an independent predictor of plaque progression at follow-up (odds ratio 1.265, 95% confidence interval 1.069 to 1.497, p = 0.006). In conclusion, NC is associated with plaque progression in patients when low-density lipoprotein cholesterol level is around 80 mg/dl at 9-month follow-up in patients with angina pectoris on rosuvastatin 10 mg/day. PMID- 21029820 TI - Smoking is associated with depletion of circulating endothelial progenitor cells and elevated pulmonary artery systolic pressure in patients with coronary artery disease. AB - Smoking is associated with depletion of endothelial progenitor cells (EPCs) and may subsequently contribute to the development of vascular dysfunction. The aim of this study was to investigate the relation between circulating EPCs and pulmonary artery systolic pressure (PASP) as determined by flow cytometry and echocardiography in 174 patients (mean age 69 +/- 9 years, 95 smokers) with established coronary artery disease. Smokers had significantly lower circulating log CD34/KDR(+) (0.86 +/- 0.03 vs 0.96 +/- 0.03 * 10-3/ml, p = 0.032) and log CD133/KDR(+) (0.68 +/- 0.03 vs 0.82 +/- 0.03 * 10-3/ml, p = 0.002) EPCs and a higher prevalence of elevated PASP >30 mm Hg (52% vs 30%, p = 0.001) than nonsmokers. Smokers with elevated PASP also had significantly lower circulating log CD34/KDR(+) (0.74 +/- 0.04 vs 0.88 +/- 0.06 * 10-3/ml, p <0.001) and log CD133/KDR(+) (0.61 +/- 0.04 vs 0.78 +/- 0.05 * 10-3/ml, p <0.001) EPCs, higher pulmonary vascular resistance, and larger right ventricular dimensions with impaired function (all p values <0.05). Log CD34/KDR(+) and log CD133/KDR(+) EPC counts were significantly and negatively correlated with PASP (r = -0.30, p <0.001, and r = -0.34, p <0.001, respectively) and pulmonary vascular resistance (r = -0.29, p = 0.002, and r = -0.18, p = 0.013, respectively). In conclusion, this study demonstrated that in patients with coronary artery disease, smoking was associated with a reduced number of EPCs and elevated PASP. This suggests that in smokers, depletion of circulating EPCs might be linked to the occurrence of pulmonary vascular dysfunction. PMID- 21029821 TI - Safety and efficacy of ezetimibe/simvastatin combination versus atorvastatin alone in adults >=65 years of age with hypercholesterolemia and with or at moderately high/high risk for coronary heart disease (the VYTELD study). AB - Higher than 80% of coronary heart disease-related mortality occurs in patients >=65 years of age. Guidelines recommend low-density lipoprotein (LDL) cholesterol targets for these at-risk patients; however, few clinical studies have evaluated lipid-lowering strategies specifically in older adults. This multicenter, 12 week, randomized, double-blind, parallel-group trial evaluated the efficacy and safety of the usual starting dose of ezetimibe/simvastatin (10/20 mg) versus atorvastatin 10 or 20 mg and the next higher dose of ezetimibe/simvastatin (10/40 mg) versus atorvastatin 40 mg in 1,289 hypercholesterolemic patients >=65 years of age with or without cardiovascular disease. Patients randomized to ezetimibe/simvastatin had greater percent decreases in LDL cholesterol (-54.2% for 10/20 mg vs -39.5% and -46.6% for atorvastatin 10 and 20 mg, respectively; 59.1% for 10/40 mg vs -50.8% for atorvastatin 40 mg; p <0.001 for all comparisons) and the number attaining LDL cholesterol <70 mg/dl (51.3% for 10/20 mg, 68.2% for 10/40 mg) and <100 mg/dl (83.6% for 10/20 mg; 90.3% for 10/40 mg) was significantly larger compared to those receiving atorvastatin for all prespecified dose comparisons (p <0.05 to <0.001). A significantly larger percentage of high-risk patients achieved LDL cholesterol <70 mg/dl on ezetimibe/simvastatin 10/20 mg (54.3%) versus atorvastatin 10 mg (10.9%, p <0.001) or 20 mg (28.9%, p <0.001) and ezetimibe/simvastatin 10/40 mg (69.2%) versus atorvastatin 40 mg (38.2%, p <0.001), and a significantly larger percentage of intermediate-risk patients achieved LDL cholesterol <100 mg/dl on ezetimibe/simvastatin 10/20 mg (82.1%) versus atorvastatin 10 mg (59.3%, p <0.05). Improvements in non-high-density lipoprotein cholesterol, total cholesterol, apolipoprotein B, and lipoprotein ratios were significantly greater with ezetimibe/simvastatin than atorvastatin for all comparisons (p <0.01 to <0.001). High-density lipoprotein cholesterol and triglyceride results were variable. All treatments were generally well tolerated. In conclusion, ezetimibe/simvastatin provided significantly greater improvements in key lipid parameters and higher attainment of LDL cholesterol targets than atorvastatin, with comparable tolerability. PMID- 21029822 TI - Usefulness of apolipoprotein B/apolipoprotein A-I ratio to predict coronary artery disease independent of the metabolic syndrome in African Americans. AB - Studies have demonstrated that the apolipoprotein B/apolipoprotein A-I (apoB/apoA I) ratio predicts cardiovascular risk better than any of the cholesterol indexes. A number of factors that define the metabolic syndrome (MS) differ across African American and European-American ethnicities. We assessed the relation of the apoB/apoA-I ratio to MS and coronary artery disease (CAD) in 224 African Americans and 304 European Americans. The MS was defined using the revised National Cholesterol Education Program Adult Treatment Panel III criteria, and CAD was assessed as >=50% stenosis or a continuous cardiovascular score (0 to 75). The European Americans had a greater apoB/apoA-I ratio than the African Americans (1.15 vs 1.07, p = 0.008). The apoB/apoA-I ratio was associated with presence of the MS in both European Americans (odds ratio 5.9, 95% confidence interval 2.53 to 13.57, p <0.001) and African Americans (odds ratio 8.3, 95% confidence interval 3.52 to 19.25, p <0.001) and was greater in subjects with the MS than in those without the MS (1.21 vs 1.04, p <0.001, for European Americans and 1.20 vs 0.94, p <0.001, for African Americans). A stepwise increase was seen in the prevalence of the MS across the apoB/apoA-I ratio tertiles in both ethnic groups (chi-square = 13.1, p <0.001, for European Americans and chi-square = 19.6, p <0.001, for African Americans). On multiple regression analyses, the apoB/apoA-I ratio independently predicted CAD in African Americans (beta = 0.242, p = 0.011). The cardiovascular score was significantly increased across the apoB/apoA-I ratio tertiles in the European-American subjects with the MS (p = 0.001). However, this association was seen in the African-American subjects without the MS (p = 0.023). In conclusion, the apoB/apoA-I ratio differed across ethnicities and was associated with presence of the MS in both groups. Among African Americans, an elevated apoB/apoA-I ratio independently predicted a greater risk of CAD. PMID- 21029823 TI - Relation between obesity and the attainment of optimal blood pressure and lipid targets in high vascular risk outpatients. AB - Obesity is associated with hypertension, dyslipidemia, and diabetes, but it is also an independent cardiovascular risk factor. We sought to evaluate the differences in treatment patterns and attainment of guideline-recommended targets among high-risk vascular outpatients in relation to their body mass index (BMI). The prospective Vascular Protection and Guideline Orientated Approach to Lipid Lowering Registries recruited 7,357 high-risk vascular outpatients in Canada from 2001 to 2004. We stratified the patient population into 3 groups according to their BMI: normal weight (BMI <24.9 kg/m2), overweight (BMI 25 to 29.9 kg/m2), and obese (BMI >30 kg/m2). We evaluated the rates of attainment for contemporary guideline targets of blood pressure (<140/90 or <130/80 mm Hg in the presence of diabetes) and lipids (low-density lipoprotein [LDL] <2.5 mmol/L [96.7 mg/dl] and total cholesterol [TC]/high-density lipoprotein [HDL] ratio <4.0). Of the 7,357 patients, 1,305 (17.7%) were normal weight, 2,791 (37.9%) overweight, and 3,261 (44.4%) obese, as determined by the BMI. Obese patients were younger and more likely to have hypertension and diabetes (all p <0.001 for trend). Obese patients had higher baseline blood pressure, TC, LDL cholesterol, triglyceride levels and TC/HDL ratio, and lower HDL cholesterol. Obese patients were more likely to be treated with antihypertensive agents (p = 0.002), angiotensin-converting enzyme inhibitors (p = 0.024), angiotensin receptor blockers (p <0.001), and high-dose statin therapy (p = 0.001). On multivariable analyses, obese patients were less likely to attain the blood pressure (odds ratio 0.77, 95% confidence interval 0.66 to 0.90, p = 0.001) and TC/HDL ratio (odds ratio 0.48, 95% confidence interval 0.42 to 0.55, p <0.001) targets but not the LDL targets (odds ratio 0.89, 95% confidence interval 0.78 to 1.03, p = 0.11). In conclusion, only a minority ambulatory patients at high cardiovascular risk achieved both guideline recommended blood pressure and lipid targets, and this significant treatment gap was more pronounced among obese patients. Our findings underscore the opportunity to optimize the treatment of these high-risk patients. PMID- 21029824 TI - Usefulness of vernakalant hydrochloride injection for rapid conversion of atrial fibrillation. AB - The objective of the present study was to assess the safety and effectiveness of vernakalant hydrochloride injection (RSD1235), a novel antiarrhythmic drug, for the conversion of atrial fibrillation (AF) or atrial flutter to sinus rhythm (SR). Patients with either AF or atrial flutter were randomized in a 1:1 ratio to receive vernakalant (n = 138) or placebo (n = 138) and were stratified by an arrhythmia duration of >3 hours to <=7 days (short duration) and 8 to <=45 days (long duration). The first infusion of placebo or vernakalant (3 mg/kg) was given for 10 minutes followed by a second infusion of placebo or vernakalant (2 mg/kg) 15 minutes later if the arrhythmia had not terminated. A total of 265 patients were randomized and received treatment. The primary end point was conversion of AF to SR for >=1 minute within 90 minutes of the start of the drug infusion in the short-duration AF group. Of the 86 patients receiving vernakalant in the short-duration AF group, 44 (51.2%) demonstrated conversion to SR compared to 3 (3.6%) of the 84 in the placebo group (p <0.0001). The median interval to conversion of short-duration AF to SR in the responders given vernakalant was 8 minutes. Of the entire AF population (short- and long-duration AF), 47 (39.8%) of the 118 vernakalant patients experienced conversion of AF to SR compared to 4 (3.3%) of the 121 placebo patients (p <0.0001). Transient dysgeusia and sneezing were the most common adverse events in the vernakalant patients. One vernakalant patient who had severe aortic stenosis experienced hypotension and ventricular fibrillation and died. In conclusion, vernakalant demonstrated a rapid and high rate of conversion for short-duration AF and was well tolerated. PMID- 21029825 TI - Meta-analysis of the effectiveness and safety of catheter ablation of atrial fibrillation in patients with versus without left ventricular systolic dysfunction. AB - Catheter ablation is a promising therapy for atrial fibrillation (AF), but its utility in patients with left ventricular systolic dysfunction (LVSD) is uncertain. The objectives of this study were to perform a systematic review and meta-analysis of randomized and observational studies comparing the rates of recurrent AF, atrial tachycardia (AT), and complications after AF catheter ablation in those with versus without LVSD and to summarize the impact of catheter ablation on the left ventricular ejection fraction. Seven observational studies and 1 randomized trial were included (total n = 1,851). Follow-up ranged from 6 to 27 months. In those with LVSD, 28% to 55% were free of AF or AT on follow-up after 1 AF catheter ablation, increasing to 64% to 96% after a mean of 1.4 procedures. The relative risk for recurrent AF or AT in those with versus without LVSD was 1.5 (95% confidence interval 1.2 to 1.8, p <0.001) after 1 procedure and 1.2 (95% confidence interval 0.9 to 1.5, p = 0.2) after multiple procedures. No difference in complications was observed in patients with (3.5%) versus without (2.5%) heart failure (p = 0.55). After catheter ablation, those with LVSD experienced a pooled absolute improvement in the left ventricular ejection fraction of 0.11 (95% confidence interval 0.07 to 0.14, p <0.001). In conclusion, patients with and without LVSD had similar risk for recurrent AF or AT after catheter ablation, but repeat procedures were required more often in those with LVSD. Significant improvements in left ventricular ejection fractions after ablation were observed in those with LVSD. Randomized trials are needed given the limitations of present data. PMID- 21029826 TI - Effect of spironolactone on left ventricular ejection fraction and volumes in patients with class I or II heart failure. AB - The beneficial effects of spironolactone in chronic heart failure (HF) have been demonstrated in patients with New York Heart Association (NYHA) class III to IV HF. This study examined the effect of spironolactone on left ventricular (LV) function and functional capacity of patients with mild to moderate HF (NYHA class I to II). One hundred sixty-eight patients with NYHA class I to II HF and LV ejection fraction <=40% were randomized to spironolactone or placebo and assessed by echocardiography, gated single-photon emission computed tomography, technetium 99m sestamibi single-photon emission computed tomographic radionuclide ventriculography, and cardiopulmonary exercise testing at baseline and after 6 months of treatment. In the spironolactone group LV ejection fraction increased from 35.2 +/- 0.7% to 39.1 +/- 3.5% (p <0.001), with a decrease in LV end diastolic and end-systolic volumes and myocardial mass and an improvement in LV diastolic filling pattern. Cardiopulmonary exercise testing parameters did not change. In conclusion, administration of spironolactone to patients with NYHA class I to II HF has beneficial effects on LV remodeling and diastolic function. PMID- 21029827 TI - Effect of renal function on survival after implantable cardioverter defibrillator placement. AB - Implantable cardioverter defibrillators (ICDs) are effective at reducing arrhythmic death in patients with left ventricular dysfunction, but few studies have investigated the outcomes after ICD implantation in patients with chronic kidney disease (CKD). We conducted a 2-center retrospective study of 958 patients who had undergone ICD placement for primary prevention from the 2000 to 2006. The patients were stratified into 5 groups according to the CKD stage (stage 1, glomerular filtration [GFR] 90 to 120 ml/min; stage 2, GFR 60 to 89 ml/min; stage 3, GFR 30 to 59 ml/min; stage 4, GFR 15 to 29 ml/min; and stage 5, GFR 0 to 14 ml/min). The primary end point was death at 1 year. Of the 958 patients included in our analysis, 73 (7.6%) had died at 1 year. The mortality rate at 1 year increased with worsening CKD (1.8%, 5.3%, 9.0%, 22%, and 38% for stage 1 to 5, respectively, p <0.0001 for group). CKD was an independent predictor of mortality; hazard ratio 1.0, 1.075 (95% confidence interval 0.578 to 2.0), 1.372 (95% confidence interval 0.736 to 2.556), 3.092 (95% confidence interval 1.52 to 6.29), and 10.15 (95% confidence interval 4.25 to 24.23) for stage 1 to 5, respectively (p <0.0001 for group). Patients with CKD and left ventricular dysfunction have a poor prognosis despite ICD placement. The 1-year mortality increased as the renal function decreased. In conclusion, physicians should be cognizant of the prognosis when considering whether an ICD should be implanted in patients with CKD. PMID- 21029828 TI - Timing and significance of exercise-induced left ventricular outflow tract pressure gradients in hypertrophic cardiomyopathy. AB - The relation of exercise-induced left ventricular (LV) outflow tract obstruction to functional capacity in hypertrophic cardiomyopathy (HC) is incompletely defined. Thus, we assessed the patterns of onset of physiologically provoked LV outflow gradients and exercise performance in 74 consecutive patients with HC (age 45 +/- 16 years; 74% men) without LV outflow obstruction at rest. The subaortic gradients were measured serially using echocardiography in these 74 patients during maximum, symptom-limited, upright bicycle exercise testing. The time course of the provoked gradients and the relation to exercise performance were assessed. Of the 74 patients, 30 (41%) developed a dynamic LV outflow gradient of >=30 mm Hg (mean 78 +/- 37 mm Hg) during upright exercise testing that correlated highly with the gradients measured with the patients supine during the immediate recovery period (R2 = 0.97). The 16 patients in whom outflow obstruction developed rapidly at low exercise levels (<=5 METs) had a significantly reduced exercise capacity (6.1 +/- 1.3 vs 8.0 +/- 1.6 METs; p <0.01) compared to the other 14 patients in whom obstruction appeared later at greater exercise levels of >5 METs. The timing of the gradient onset was not predictable from the baseline clinical and echocardiographic features, peak exercise LV outflow tract gradient, or symptoms. In conclusion, in patients with HC without outflow obstruction at rest, the earlier onset of LV outflow tract gradients during physiologic exercise was associated with impaired exercise performance. These findings have provided insights into the determinants of functional impairment in HC and support the potential value of exercise echocardiography in the clinical assessment of patients with HC. PMID- 21029829 TI - Comparison of acute reduction in left ventricular outflow tract pressure gradient in obstructive hypertrophic cardiomyopathy by disopyramide versus pilsicainide versus cibenzoline. AB - Negative inotropic agents are often administered to decrease the left ventricular (LV) pressure gradient in patients with obstructive hypertrophic cardiomyopathy (HC). Little information is available regarding comparisons of the effects on LV pressure gradient among negative inotropic agents. The present study compared the decrease in the LV pressure gradient at rest in patients with obstructive HC after treatment with pilsicainide versus treatment with disopyramide or cibenzoline. The LV pressure gradient and LV function were assessed before and after the intravenous administration of each drug. In 12 patients (group A, mean pressure gradient 90 +/- 24 mm Hg), the effects of disopyramide, propranolol, and verapamil were compared. In another 12 patients (group B, mean pressure gradient 98 +/- 34 mm Hg), a comparison was performed among disopyramide, cibenzoline, and pilsicainide. In group A, the percentage of reduction in the LV pressure gradient was 7.7 +/- 9.9% with verapamil, 19.0 +/- 20.2% with propranolol, and 58.6 +/- 15.0% with disopyramide, suggesting that disopyramide was more effective than either verapamil or propranolol. In group B, the percentage of reduction in the LV pressure gradient was 55.3 +/- 26.6% with disopyramide, 55.3 +/- 20.6% with cibenzoline, and 54.7 +/- 15.4% with pilsicainide, suggesting an equivalent effect on the LV pressure gradient for these 3 agents. In conclusion, these results indicate that the acute efficacy for the reduction of the LV pressure gradient at rest by pilsicainide (a pure sodium channel blocker) was equivalent to that of disopyramide or cibenzoline (combined sodium and calcium channel blockers). Accordingly, sodium channel blockade might be more important for reducing the LV pressure gradient at rest in patients with obstructive HC than calcium channel blockade or beta blockade. PMID- 21029830 TI - Drink more, and eat less: advice in obstructive hypertrophic cardiomyopathy. AB - This report describes a series of symptomatic patients with obstructive hypertrophic cardiomyopathy with significant postprandial hemodynamic changes. This finding was identified by history, clinical examination, and echocardiography in 6 consecutive symptomatic patients referred for the evaluation of ventricular septal reduction therapy. Counseling these patients with dietary changes to include small frequent meals and to increase noncaffeinated fluid intake resulted in reductions in symptoms. In conclusion, severe symptoms in obstructive hypertrophic cardiomyopathy unresponsive to pharmacologic treatment frequently result in referral for definitive septal reduction therapy through surgery or, less frequently, alcohol septal ablation therapy. However, recognition of postprandial exacerbation in symptomatic patients may allow for nonpharmacologic dietary interventions that may obviate the need for more invasive therapies and their associated complications. PMID- 21029831 TI - Contraception in women with congenital heart disease. AB - The present study reports on contraceptive use, methods used, and counseling received on contraceptive issues for women with congenital heart disease and provides a brief review of current knowledge of the risks in relation to the different cardiac situations encountered with these specific patients. A total of 536 consecutive adult women with congenital heart disease (median age 29 years) were recruited from 2 tertiary care centers. They underwent a clinical assessment and completed a questionnaire regarding their contraceptive use. Oral contraceptives, condoms, and intrauterine devices were the most commonly used methods. Pregnancy occurred in almost every tenth woman despite the use of contraception. We identified a substantial number of women (20%) who were presently using contraceptive methods that were contraindicated for their specific cardiac condition. Additionally, a high proportion of patients (28%), in the group with high pregnancy-associated risks, were not using contraception despite having a sexual relationship. In our study, 43% of the women had not been counseled about contraception, and 48% had not been informed of the pregnancy related risks by their treating physician. In conclusion, timely and competent counseling about contraception is important for women with congenital heart disease. Collaboration between cardiologists and gynecologists should be strengthened. Failure to give adequate family planning advice to this patient group could have hazardous consequences, causing an unnecessary risk to mother and child. PMID- 21029832 TI - Late mortality among Danish patients with congenital heart defect. AB - To examine long-term mortality in Danish patients with congenital heart defect (CHD), we performed a population-based follow-up study using nationwide registries. We identified all children born in Denmark from January 1, 1977 to January 1, 2006 from the Danish Civil Registration System. Children with a primary diagnosis of CHD, diagnosed before 1 year of age, were then identified in the National Registry of Patients. We computed cumulative mortality of patients and the background population according to birth period (1977 to 1986, 1987 to 1996, and 1997 to 2005). We identified 6,646 patients with CHDs. Overall cumulative mortality estimates in patients with CHDs at 1 year and 10 and 25 years of age were 20% (95% confidence interval [CI] 19 to 21), 25% (95% CI 24 to 26), and 28% (95% CI 27 to 30). In Danes born in the same period equivalent mortality estimates were 0.6% (95% CI 0.6 to 0.6), 0.8% (95% CI 0.7 to 0.8), and 1.3% (95% CI 1.3 to 1.3). Mortality differed substantially according to heart defect type and mortality at 10 years of age ranged from 9% (95% CI 6 to 12) in patients with atrial septal defects (n = 361) to 55% (95% CI 45 to 66) in patients with common arterial trunk (n = 78). Mortality decreased during the study period; 1-year mortality was 28% (95% CI 26 to 31) for patients born from 1977 to 1986 (n = 2,907) compared to 13% (95% CI 12 to 15) for patients born from 1997 to 2005 (n = 2,741). Mortality decreased in all heart defect type categories. In conclusion, mortality in patients with CHD was high compared to the general population, especially in infancy, but also after 10 years of age, emphasizing the need for long-term medical follow up. Mortality at 1 year of age has decreased substantially during recent decades. PMID- 21029833 TI - Usefulness of stenting in aortic coarctation in patients with the Turner syndrome. AB - We report our experience with stent implantation for treatment of aortic coarctation in patients with Turner syndrome. Ten consecutive patients with Turner syndrome and aortic coarctation (median age 12 years, range 9 to 24) underwent coarctation stenting. Of these, 6 patients were treated for isolated coarctation and 4 for recurrent coarctation (3 after balloon dilation and 1 after balloon dilation and surgical repair). Bare metal stents were implanted in 7 patients and covered stents in 3. Immediately after stent implantation, peak systolic gradient decreased from 46.1 +/- 24.3 to 1.9 +/- 2.1 mm Hg (p <0.001). Aortic diameter at coarctation site increased from 5.1 +/- 3.2 to 15.3 +/- 2.0 mm after stenting (p <0.001). There were no deaths or procedure-related complications. During a median follow-up of 30.5 months, no patient developed restenosis. Two patients developed late aortic aneurysms at the coarctation site. In conclusion, stent implantation for aortic coarctation in patients with Turner syndrome appears to be a safe and effective alternative to surgical repair. Larger cohorts and longer-term follow-up are required to determine the effects of the procedure on the aortic wall. PMID- 21029834 TI - Long-term outcomes in children with pulmonary arterial hypertension treated with bosentan in real-world clinical settings. AB - Treatment algorithms in pediatric pulmonary arterial hypertension (PAH) are derived from clinical trials in adult populations and from clinical practice, but experience in children is limited. In this retrospective cohort study, we analyzed outcomes in a previously identified cohort of 86 consecutive children with PAH treated with bosentan as part of their treatment regimen. All children with idiopathic PAH or heritable PAH and PAH associated with congenital heart disease or connective tissue disease who started bosentan treatment from May 2001 to April 2003 in 2 tertiary pediatric referral centers were followed, with data collection ending August 2006. Eighty-six children (37 male, 49 female) 11 +/- 5 years of age with idiopathic/heritable PAH (n = 36), PAH associated with congenital heart disease (n = 48), or PAH associated with connective tissue disease (n = 2) received bosentan as monotherapy (n = 42) or as an add-on to pre existing continuous intravenous epoprostenol or subcutaneous treprostinil (n = 44). Median observation period was 39 months (range 2 to 60). Thirty-four patients (40%) received >=1 additional PAH-specific therapy during follow-up. At end of data collection, 25 patients (29%) remained on bosentan, 43 (50%) had stopped bosentan, 11 (13%) had died while on bosentan, and 7 were lost to follow up. At 4 years, the Kaplan-Meier estimate of disease progression in patients while on bosentan was 54% (7 patients at risk) with a survival estimate of 82% (16 patients at risk). Risk factors significantly associated with survival were World Health Organization functional class and indexed pulmonary vascular resistance. In conclusion, outcome in children with PAH managed with current treatment regimens appears favorable. However, despite current therapy options, disease progression remains a concern. PMID- 21029835 TI - Feasibility and clinical utility of transesophageal echocardiography in the acute phase of cerebral ischemia. AB - We evaluated the feasibility and clinical utility of transesophageal echocardiography (TEE) in the early management of ischemic stroke. TEE was performed in consecutive patients with acute cerebral ischemia within 48 hours of symptoms onset. The data were analyzed by age (<55 vs >=55 years), and the baseline stroke etiology was classified (determined vs undetermined). TEE was feasible in 660 (61%) of 1,080 patients. Left atrial abnormalities and complicated aortic plaques prevailed in older patients (p <0.05), irrespective of the stroke etiology. A patent foramen ovale prevailed in younger patients (p <0.05) but even in older patients was present in 13% of the determined and 31% of the undetermined stroke subgroups. Overall, high-risk and potentially high-risk cardioembolic sources were detected in 47% of the patients, and stroke etiology was consequently reviewed: 40% of the baseline undetermined strokes were reclassified as cardioembolic, and 29% of lacunar, 42% of large artery, and 30% of other determined-cause strokes were reclassified as concurrent etiology. Subsequently, according to the current guidelines, 12% of patients were reassigned from antiplatelet to anticoagulant therapy and 17% of patients were treated with high-dose statins; overall, secondary prevention treatment was modified in 26% of patients. In conclusion, TEE was feasible in about 2/3 of the patients investigated within 48 hours of the index event, contributed to stroke classification in 1/3 of cases, and guided secondary prevention therapy in 1/4 of patients. Therefore, TEE is useful for defining patients' risk profile for stroke recurrence. PMID- 21029836 TI - Comparison of left and right atrial volume by echocardiography versus cardiac magnetic resonance imaging using the area-length method. AB - Increased atrial volumes predict adverse cardiovascular events. Accordingly, accurate measurement of atrial size has become increasingly important in clinical practice. The area-length method is commonly used to estimate the volume. Disagreements between atrial volumes using echocardiography and other imaging modalities have been found. It is unclear whether this has resulted from differences in the measurement method or discrepancies among imaging modalities. We compared the right atrial (RA) and left atrial (LA) volume estimates using the area-length method for transthoracic echocardiography and cardiovascular magnetic resonance (CMR) imaging. Patients undergoing echocardiography and CMR imaging within 1 month were identified retrospectively. For both modalities, the RA and LA long-axis dimension and area were measured using standard 2- and 4-chamber views, and the volume was calculated using the area-length method for both atria. The echocardiographic and CMR values were compared using the Bland-Altman method. A total of 85 patients and 18 controls were included in the present study. The atrial volumes estimated using the area-length method were significantly smaller when measured using echocardiography than when measured using CMR imaging (LA volume 35 +/- 20 vs 49 +/- 30 ml/m2, p <0.001, and RA volume 32 +/- 23 vs 43 +/- 29 ml/m2, p = 0.012). The mean difference (CMR imaging minus echocardiography) was 14 +/- 14 ml/m2 for the LA and 10 +/- 16 ml/m2 for the RA volume. Similar results were found in the healthy controls. No significant intra- or interobserver variability was found within each modality. In conclusion, echocardiography consistently underestimated the atrial volumes compared to CMR imaging using the area-length method. PMID- 21029837 TI - The JUPITER Trial: responding to the critics. PMID- 21029838 TI - Statin therapy in primary prevention: new insights regarding women and the elderly. PMID- 21029839 TI - Pathogenesis of the Takotsubo syndrome: a unifying hypothesis. AB - The takotsubo syndrome (TS) is defined by a constellation of clinical observations in a subgroup of patients with acute coronary syndromes. Separating patients with TS from the general population with acute ischemic events are 2 important findings: obstructive coronary artery disease is missing, but the sine qua non is a distinctive pattern of abnormal left ventricular contraction. As with many newly recognized clinical syndromes, TS seems not to conform to accepted pathogenetic mechanisms. Thus, physicians are challenged to identify previously unrecognized mechanisms of disease. Two schools of thought have emerged in this regard. Most consider its pathogenesis to be a stress-induced neurohormonal phenomenon, while a smaller but substantial group believe that the transient occlusion of an epicardial coronary artery is responsible and that the syndrome is simply an unusual manifestation of coronary atherosclerosis. This editorial outlines briefly the evidence for each of these positions and presents a novel construct that may encompass the 2 views. Central to this unifying hypothesis is the belief that a neurohormonal surge triggers the hallmark left ventricular contraction abnormality, the sine qua non of the TS. In conclusion, the authors postulate that this pattern will result regardless of the state of the epicardial coronary arteries and can be observed in patients with angiographically normal coronary arteries, as well as those with obstructed or occluded arteries. PMID- 21029840 TI - It's the cholesterol, stupid! PMID- 21029841 TI - A contemporary meta-analysis of gender differences in mortality after coronary artery bypass grafting. PMID- 21029842 TI - Could Paclitaxel-eluting stents be superior to sirolimus-eluting stents for the treatment of saphenous vein graft lesions? PMID- 21029843 TI - Do advanced practice nurses or physician assistants outperform cardiologists? PMID- 21029844 TI - [Solution to case 21. Chronic recurrent multifocal osteomyelitis]. PMID- 21029845 TI - [Solution to case 22. Tuberculous peritonitis]. PMID- 21029846 TI - Genome simulation approaches for synthesizing in silico datasets for human genomics. AB - Simulated data is a necessary first step in the evaluation of new analytic methods because in simulated data the true effects are known. To successfully develop novel statistical and computational methods for genetic analysis, it is vital to simulate datasets consisting of single nucleotide polymorphisms (SNPs) spread throughout the genome at a density similar to that observed by new high throughput molecular genomics studies. In addition, the simulation of environmental data and effects will be essential to properly formulate risk models for complex disorders. Data simulations are often criticized because they are much less noisy than natural biological data, as it is nearly impossible to simulate the multitude of possible sources of natural and experimental variability. However, simulating data in silico is the most straightforward way to test the true potential of new methods during development. Thus, advances that increase the complexity of data simulations will permit investigators to better assess new analytical methods. In this work, we will briefly describe some of the current approaches for the simulation of human genomics data describing the advantages and disadvantages of the various approaches. We will also include details on software packages available for data simulation. Finally, we will expand upon one particular approach for the creation of complex, human genomic datasets that uses a forward-time population simulation algorithm: genomeSIMLA. Many of the hallmark features of biological datasets can be synthesized in silico; still much research is needed to enhance our capabilities to create datasets that capture the natural complexity of biological datasets. PMID- 21029847 TI - Logic regression and its extensions. AB - Logic regression is an adaptive classification and regression procedure, initially developed to reveal interacting single nucleotide polymorphisms (SNPs) in genetic association studies. In general, this approach can be used in any setting with binary predictors, when the interaction of these covariates is of primary interest. Logic regression searches for Boolean (logic) combinations of binary variables that best explain the variability in the outcome variable, and thus, reveals variables and interactions that are associated with the response and/or have predictive capabilities. The logic expressions are embedded in a generalized linear regression framework, and thus, logic regression can handle a variety of outcome types, such as binary responses in case-control studies, numeric responses, and time-to-event data. In this chapter, we provide an introduction to the logic regression methodology, list some applications in public health and medicine, and summarize some of the direct extensions and modifications of logic regression that have been proposed in the literature. PMID- 21029849 TI - Multigenic modeling of complex disease by random forests. AB - The genetics and heredity of complex human traits have been studied for over a century. Many genes have been implicated in these complex traits. Genome-wide association studies (GWAS) were designed to investigate the association between common genetic variation and complex human traits using high-throughput platforms that measured hundreds of thousands of common single-nucleotide polymorphisms (SNPs). GWAS have successfully identified many novel genetic loci associated with complex traits using a univariate regression-based approach. Even for traits with a large number of identified variants, only a small fraction of the interindividual variation in risk phenotypes has been explained. In biological systems, protein, DNA, RNA, and metabolites frequently interact to each other to perform their biological functions, and to respond to environmental factors. The complex interactions among genes and between the genes and environment may partially explain the "missing heritability." The traditional regression-based methods are limited to address the complex interactions among the hundreds of thousands of SNPs and their environmental context by both the modeling and computational challenge. Random Forests (RF), one of the powerful machine learning methods, is regarded as a useful alternative to capture the complex interaction effects among the GWAS data, and potentially address the genetic heterogeneity underlying these complex traits using a computationally efficient framework. In this chapter, the features of prediction and variable selection, and their applications in genetic association studies are reviewed and discussed. Additional improvements of the original RF method are warranted to make the applications in GWAS to be more successful. PMID- 21029848 TI - Complex system approaches to genetic analysis Bayesian approaches. AB - Genetic epidemiology is increasingly focused on complex diseases involving multiple genes and environmental factors, often interacting in complex ways. Although standard frequentist methods still have a role in hypothesis generation and testing for discovery of novel main effects and interactions, Bayesian methods are particularly well suited to modeling the relationships in an integrated "systems biology" manner. In this chapter, we provide an overview of the principles of Bayesian analysis and their advantages in this context and describe various approaches to applying them for both model building and discovery in a genome-wide setting. In particular, we highlight the ability of Bayesian methods to construct complex probability models via a hierarchical structure and to account for uncertainty in model specification by averaging over large spaces of alternative models. PMID- 21029850 TI - Detecting, characterizing, and interpreting nonlinear gene-gene interactions using multifactor dimensionality reduction. AB - Human health is a complex process that is dependent on many genes, many environmental factors and chance events that are perhaps not measurable with current technology or are simply unknowable. Success in the design and execution of population-based association studies to identify those genetic and environmental factors that play an important role in human disease will depend on our ability to embrace, rather that ignore, complexity in the genotype to phenotype mapping relationship for any given human ecology. We review here three general computational challenges that must be addressed. First, data mining and machine learning methods are needed to model nonlinear interactions between multiple genetic and environmental factors. Second, filter and wrapper methods are needed to identify attribute interactions in large and complex solution landscapes. Third, visualization methods are needed to help interpret computational models and results. We provide here an overview of the multifactor dimensionality reduction (MDR) method that was developed for addressing each of these challenges. PMID- 21029852 TI - Statistical methods for pathway analysis of genome-wide data for association with complex genetic traits. AB - A number of statistical methods have been developed to test for associations between pathways (collections of genes related biologically) and complex genetic traits. Pathway analysis methods were originally developed for analyzing gene expression data, but recently methods have been developed to perform pathway analysis on genome-wide association study (GWAS) data. The purpose of this review is to give an overview of these methods, enabling the reader to gain an understanding of what pathway analysis involves, and to select the method most suited to their purposes. This review describes the various types of statistical methods for pathway analysis, detailing the strengths and weaknesses of each. Factors influencing the power of pathway analyses, such as gene coverage and choice of pathways to analyze, are discussed, as well as various unresolved statistical issues. Finally, a list of computer programs for performing pathway analysis on genome-wide association data is provided. PMID- 21029851 TI - The restricted partition method. AB - For many complex traits, the bulk of the phenotypic variation attributable to genetic factors remains unexplained, even after well-powered genome-wide association studies. Among the multiple possible explanations for the "missing" variance, joint effects of multiple genetic variants are a particularly appealing target for investigation: they are well documented in biology and can often be evaluated using existing data. The first two sections of this chapter discusses these and other concerns that led to the development of the Restricted Partition Method (RPM). The RPM is an exploratory tool designed to investigate, in a model agnostic manner, joint effects of genetic and environmental factors contributing to quantitative or dichotomous phenotypes. The method partitions multilocus genotypes (or genotype-environmental exposure classes) into statistically distinct "risk" groups, then evaluates the resulting model for phenotypic variance explained. It is sensitive to factors whose effects are apparent only in a joint analysis, and which would therefore be missed by many other methods. The third section of the chapter provides details of the RPM algorithm and walks the reader through an example. The final sections of the chapter discuss practical issues related to the use of the method. Because exhaustive pairwise or higher order analyses of many SNPs are computationally burdensome, much of the discussion focuses on computational issues. The RPM proved to be practical for a large candidate gene analysis, consisting of over 40,000 SNPs, using a desktop computer. Because the algorithm and software lend themselves to distributed processing, larger analyses can easily be split among multiple computers. PMID- 21029853 TI - Providing context and interpretability to genetic association analysis results using the KGraph. AB - The KGraph is a data visualization system that has been developed to display the complex relationships between the univariate and bivariate associations among an outcome of interest, a set of covariates, and a set of genetic variations such as single-nucleotide polymorphisms (SNPs). It allows for easy simultaneous viewing and interpretation of genetic associations, correlations among covariates and SNPs, and information about the replication and cross-validation of these associations. The KGraph allows the user to more easily investigate multicollinearity and confounding through visualization of the multidimensional correlation structure underlying genetic associations. It emphasizes gene environment interactions, gene-gene interactions, and correlations, all important components of the complex genetic architecture of most human traits. The KGraph was designed for use in gene-centric studies, but can be integrated into association analysis workflows as well. The software is available at http://www.epidkardia.sph.umich.edu/software/kgrapher. PMID- 21029854 TI - ATRX: Put me on repeat. AB - Mutations in the chromatin-remodeling protein ATRX cause alpha thalassaemia and mental retardation, but the severity of the disorder is independent of the specific mutation. In this issue of Cell, Law et al. (2010) demonstrate that ATRX alters gene expression by binding to G-rich tandem repeats, and the degree of transcriptional silencing caused by ATRX mutations correlates with the number of repeats. PMID- 21029855 TI - Egg's ZP3 structure speaks volumes. AB - Binding of mammalian sperm to eggs depends in part on ZP3, a glycoprotein in the egg's extracellular coat, the zona pellucida. In this issue, Han et al. (2010) describe the structure of an avian ZP3 homolog, providing insights into ZP3 processing and polymerization and the roles of the ZP3 polypeptide and its carbohydrate in sperm binding. PMID- 21029856 TI - Monocytes join the dendritic cell family. AB - Dendritic cells are professional antigen-presenting cells that mediate immunity and tolerance. Cheong et al. (2010) uncover a new route for dendritic cell production in vivo. They show that in response to infection by gram-negative bacteria, monocytes are recruited to the lymph node where they rapidly differentiate into dendritic cells that present antigens to T cells. PMID- 21029857 TI - Ephecting excitatory synapse development. AB - Alterations in synapse number and morphology are associated with devastating psychiatric and neurologic disorders. In this issue of Cell, Margolis et al. (2010) show that the RhoA-guanine exchange factor (GEF) Ephexin5 limits the numbers of excitatory synapses that neurons receive, thus identifying a new mechanism controlling synaptogenesis. PMID- 21029858 TI - Chemoaffinity revisited: dscams, protocadherins, and neural circuit assembly. AB - The chemoaffinity hypothesis for neural circuit assembly posits that axons and their targets bear matching molecular labels that endow neurons with unique identities and specify synapses between appropriate partners. Here, we focus on two intriguing candidates for fulfilling this role, Drosophila Dscams and vertebrate clustered protocadherins (Pcdhs). In each, a complex genomic locus encodes large numbers of neuronal transmembrane proteins with homophilic binding specificity, individual members of which are expressed combinatorially. Although these properties suggest that Dscams and Pcdhs could act as specificity molecules, they may do so in ways that challenge traditional views of how neural circuits assemble. PMID- 21029859 TI - DNA damage-mediated induction of a chemoresistant niche. AB - While numerous cell-intrinsic processes are known to play decisive roles in chemotherapeutic response, relatively little is known about the impact of the tumor microenvironment on therapeutic outcome. Here, we use a well-established mouse model of Burkitt's lymphoma to show that paracrine factors in the tumor microenvironment modulate lymphoma cell survival following the administration of genotoxic chemotherapy. Specifically, IL-6 and Timp-1 are released in the thymus in response to DNA damage, creating a "chemo-resistant niche" that promotes the survival of a minimal residual tumor burden and serves as a reservoir for eventual tumor relapse. Notably, IL-6 is released acutely from thymic endothelial cells in a p38-dependent manner following genotoxic stress, and this acute secretory response precedes the gradual induction of senescence in tumor associated stromal cells. Thus, conventional chemotherapies can induce tumor regression while simultaneously eliciting stress responses that protect subsets of tumor cells in select anatomical locations from drug action. PMID- 21029860 TI - ATR-X syndrome protein targets tandem repeats and influences allele-specific expression in a size-dependent manner. AB - ATRX is an X-linked gene of the SWI/SNF family, mutations in which cause syndromal mental retardation and downregulation of alpha-globin expression. Here we show that ATRX binds to tandem repeat (TR) sequences in both telomeres and euchromatin. Genes associated with these TRs can be dysregulated when ATRX is mutated, and the change in expression is determined by the size of the TR, producing skewed allelic expression. This reveals the characteristics of the affected genes, explains the variable phenotypes seen with identical ATRX mutations, and illustrates a new mechanism underlying variable penetrance. Many of the TRs are G rich and predicted to form non-B DNA structures (including G quadruplex) in vivo. We show that ATRX binds G-quadruplex structures in vitro, suggesting a mechanism by which ATRX may play a role in various nuclear processes and how this is perturbed when ATRX is mutated. PMID- 21029861 TI - Upf1 senses 3'UTR length to potentiate mRNA decay. AB - The selective degradation of mRNAs by the nonsense-mediated decay pathway is a quality control process with important consequences for human disease. From initial studies using RNA hairpin-tagged mRNAs for purification of messenger ribonucleoproteins assembled on transcripts with HIV-1 3' untranslated region (3'UTR) sequences, we uncover a two-step mechanism for Upf1-dependent degradation of mRNAs with long 3'UTRs. We demonstrate that Upf1 associates with mRNAs in a 3'UTR length-dependent manner and is highly enriched on transcripts containing 3'UTRs known to elicit NMD. Surprisingly, Upf1 recruitment and subsequent RNA decay can be antagonized by retroviral RNA elements that promote translational readthrough. By modulating the efficiency of translation termination, recognition of long 3'UTRs by Upf1 is uncoupled from the initiation of decay. We propose a model for 3'UTR length surveillance in which equilibrium binding of Upf1 to mRNAs precedes a kinetically distinct commitment to RNA decay. PMID- 21029862 TI - The long noncoding RNA, Jpx, is a molecular switch for X chromosome inactivation. AB - Once protein-coding, the X-inactivation center (Xic) is now dominated by large noncoding RNAs (ncRNA). X chromosome inactivation (XCI) equalizes gene expression between mammalian males and females by inactivating one X in female cells. XCI requires Xist, an ncRNA that coats the X and recruits Polycomb proteins. How Xist is controlled remains unclear but likely involves negative and positive regulators. For the active X, the antisense Tsix RNA is an established Xist repressor. For the inactive X, here, we identify Xic-encoded Jpx as an Xist activator. Jpx is developmentally regulated and accumulates during XCI. Deleting Jpx blocks XCI and is female lethal. Posttranscriptional Jpx knockdown recapitulates the knockout, and supplying Jpx in trans rescues lethality. Thus, Jpx is trans-acting and functions as ncRNA. Furthermore, DeltaJpx is rescued by truncating Tsix, indicating an antagonistic relationship between the ncRNAs. We conclude that Xist is controlled by two RNA-based switches: Tsix for Xa and Jpx for Xi. PMID- 21029863 TI - Microbial stimulation fully differentiates monocytes to DC-SIGN/CD209(+) dendritic cells for immune T cell areas. AB - Dendritic cells (DCs), critical antigen-presenting cells for immune control, normally derive from bone marrow precursors distinct from monocytes. It is not yet established if the large reservoir of monocytes can develop into cells with critical features of DCs in vivo. We now show that fully differentiated monocyte derived DCs (Mo-DCs) develop in mice and DC-SIGN/CD209a marks the cells. Mo-DCs are recruited from blood monocytes into lymph nodes by lipopolysaccharide and live or dead gram-negative bacteria. Mobilization requires TLR4 and its CD14 coreceptor and Trif. When tested for antigen-presenting function, Mo-DCs are as active as classical DCs, including cross-presentation of proteins and live gram negative bacteria on MHC I in vivo. Fully differentiated Mo-DCs acquire DC morphology and localize to T cell areas via L-selectin and CCR7. Thus the blood monocyte reservoir becomes the dominant presenting cell in response to select microbes, yielding DC-SIGN(+) cells with critical functions of DCs. PMID- 21029864 TI - Endophilin functions as a membrane-bending molecule and is delivered to endocytic zones by exocytosis. AB - Two models have been proposed for endophilin function in synaptic vesicle (SV) endocytosis. The scaffolding model proposes that endophilin's SH3 domain recruits essential endocytic proteins, whereas the membrane-bending model proposes that the BAR domain induces positively curved membranes. We show that mutations disrupting the scaffolding function do not impair endocytosis, whereas those disrupting membrane bending cause significant defects. By anchoring endophilin to the plasma membrane, we show that endophilin acts prior to scission to promote endocytosis. Despite acting at the plasma membrane, the majority of endophilin is targeted to the SV pool. Photoactivation studies suggest that the soluble pool of endophilin at synapses is provided by unbinding from the adjacent SV pool and that the unbinding rate is regulated by exocytosis. Thus, endophilin participates in an association-dissociation cycle with SVs that parallels the cycle of exo- and endocytosis. This endophilin cycle may provide a mechanism for functionally coupling endocytosis and exocytosis. PMID- 21029865 TI - EphB-mediated degradation of the RhoA GEF Ephexin5 relieves a developmental brake on excitatory synapse formation. AB - The mechanisms that promote excitatory synapse formation and maturation have been extensively studied. However, the molecular events that limit excitatory synapse development so that synapses form at the right time and place and in the correct numbers are less well understood. We have identified a RhoA guanine nucleotide exchange factor, Ephexin5, which negatively regulates excitatory synapse development until EphrinB binding to the EphB receptor tyrosine kinase triggers Ephexin5 phosphorylation, ubiquitination, and degradation. The degradation of Ephexin5 promotes EphB-dependent excitatory synapse development and is mediated by Ube3A, a ubiquitin ligase that is mutated in the human cognitive disorder Angelman syndrome and duplicated in some forms of Autism Spectrum Disorders (ASDs). These findings suggest that aberrant EphB/Ephexin5 signaling during the development of synapses may contribute to the abnormal cognitive function that occurs in Angelman syndrome and, possibly, ASDs. PMID- 21029867 TI - Retraction notice to: Assembly of endogenous oskar mRNA particles for motor dependent transport in the Drosophila oocyte. PMID- 21029866 TI - Nucleosome-interacting proteins regulated by DNA and histone methylation. AB - Modifications on histones or on DNA recruit proteins that regulate chromatin function. Here, we use nucleosomes methylated on DNA and on histone H3 in an affinity assay, in conjunction with a SILAC-based proteomic analysis, to identify "crosstalk" between these two distinct classes of modification. Our analysis reveals proteins whose binding to nucleosomes is regulated by methylation of CpGs, H3K4, H3K9, and H3K27 or a combination thereof. We identify the origin recognition complex (ORC), including LRWD1 as a subunit, to be a methylation sensitive nucleosome interactor that is recruited cooperatively by DNA and histone methylation. Other interactors, such as the lysine demethylase Fbxl11/KDM2A, recognize nucleosomes methylated on histones, but their recruitment is disrupted by DNA methylation. These data establish SILAC nucleosome affinity purifications (SNAP) as a tool for studying the dynamics between different chromatin modifications and provide a modification binding "profile" for proteins regulated by DNA and histone methylation. PMID- 21029868 TI - Snapshot: neural crest. PMID- 21029869 TI - Prudent use of antibacterial agents: are we entering in an era of infections with no effective antibacterial agents? What can we do? PMID- 21029870 TI - Left ventricular thrombosis refractory to medical therapy. PMID- 21029871 TI - Combination of loop diuretics with thiazide-type diuretics in heart failure. AB - Volume overload is an important clinical target in heart failure management, typically addressed using loop diuretics. An important and challenging subset of heart failure patients exhibit fluid overload despite significant doses of loop diuretics. One approach to overcome loop diuretic resistance is the addition of a thiazide-type diuretic to produce diuretic synergy via "sequential nephron blockade," first described more than 40 years ago. Although potentially able to induce diuresis in patients otherwise resistant to high doses of loop diuretics, this strategy has not been subjected to large-scale clinical trials to establish safety and clinical efficacy. We summarize the existing literature evaluating the combination of loop and thiazide diuretics in patients with heart failure in order to describe the possible benefits and hazards associated with this therapy. Combination diuretic therapy using any of several thiazide-type diuretics can more than double daily urine sodium excretion to induce weight loss and edema resolution, at the risk of inducing severe hypokalemia in addition to hyponatremia, hypotension, and worsening renal function. We provide considerations about prudent use of this therapy and review potential misconceptions about this long-used diuretic approach. Finally, we seek to highlight the need for pragmatic clinical trials for this commonly used therapy. PMID- 21029872 TI - Biomarkers in acute aortic dissection and other aortic syndromes. AB - Acute aortic syndromes have an incidence of >30 per million per annum and a high mortality without definitive treatment. Survival may relate to the speed of diagnosis. Although pain is the most common symptom, there is a large fraction of patients in whom the diagnosis may be mistaken or overlooked. Currently, a high index of clinical suspicion is the chief prompt that diverts a patient into a definitive algorithm of imaging investigations. Although there is no point-of care biochemical test that can be reliably used to positively identify dissection, biomarkers are available that could accelerate the diagnostic pathway and thereby expedite treatment. PMID- 21029873 TI - Effect of biventricular pacing on diastolic dyssynchrony. AB - OBJECTIVES: This study sought to examine the changes in diastolic dyssynchrony with cardiac resynchronization therapy (CRT). BACKGROUND: Little is known about the effect of CRT on diastolic dyssynchrony. METHODS: Consecutive heart failure patients (n = 266, age 65.7 +/- 10.0 years) underwent color-coded tissue Doppler imaging at baseline, 48 h, and 6 months after CRT. Systolic and diastolic dyssynchrony were defined as maximal time delay in peak systolic and early diastolic velocities, respectively, in 4 basal LV segments. CRT responders were defined as those with >=15% decrease in LV end-systolic volume at 6 months. RESULTS: Baseline LVEF was 25.2 +/- 8.1%; 63.5% patients were CRT responders. Baseline incidence of systolic and diastolic dyssynchrony, and a combination of both was 46.2%, 51.9%, and 28.6%, respectively. Compared to nonresponders, responders had longer baseline systolic (79.2 +/- 43.4 ms vs. 45.4 +/- 30.4 ms; p < 0.001) and diastolic (78.5 +/- 52.0 ms vs. 50.1 +/- 38.2 ms; p < 0.001) delays. In follow-up, systolic delays (45.4 +/- 31.6 ms at 48 h; 38.9 +/- 26.2 ms at 6 months; p < 0.001) and diastolic delays (49.4 +/- 36.3 ms at 48 h; 37.7 +/- 26.0 ms at 6 months; p < 0.001) improved only in responders. CONCLUSIONS: At baseline: 1) diastolic dyssynchrony was more common than systolic dyssynchrony in HF patients; 2) nonresponders had less baseline diastolic dyssynchrony compared to responders. After CRT: 1) diastolic dyssynchrony improved only in responders. Further insight into the pathophysiology of diastolic dyssynchrony and its changes with CRT may provide incremental information on patient-specific treatments. PMID- 21029874 TI - Augmented ST-segment elevation during recovery from exercise predicts cardiac events in patients with Brugada syndrome. AB - OBJECTIVES: The goal of this study was to evaluate the prevalence and the clinical significance of ST-segment elevation during recovery from exercise testing. BACKGROUND: During recovery from exercise testing, ST-segment elevation is reported in some patients with Brugada syndrome (BrS). METHODS: Treadmill exercise testing was conducted for 93 patients (91 men), 46 +/- 14 years of age, with BrS (22 documented ventricular fibrillation, 35 syncope alone, and 36 asymptomatic); and for 102 healthy control subjects (97 men), 46 +/- 17 years of age. Patients were routinely followed up. The clinical end point was defined as the occurrence of sudden cardiac death, ventricular fibrillation, or sustained ventricular tachyarrhythmia. RESULTS: Augmentation of ST-segment elevation >=0.05 mV in V(1) to V(3) leads compared with baseline was observed at early recovery (1 to 4 min at recovery) in 34 BrS patients (37% [group 1]), but was not observed in the remaining 59 BrS patients (63% [group 2]) or in the 102 control subjects. During 76 +/- 38 months of follow-up, ventricular fibrillation occurred more frequently in group 1 (15 of 34, 44%) than in group 2 (10 of 59, 17%; p = 0.004). Multivariate Cox regression analysis showed that in addition to previous episodes of ventricular fibrillation (p = 0.005), augmentation of ST-segment elevation at early recovery was a significant and independent predictor for cardiac events (p = 0.007), especially among patients with history of syncope alone (6 of 12 [50%] in group 1 vs. 3 of 23 [13%] in group 2) and among asymptomatic patients (3 of 15 [20%] in group 1 vs. 0 of 21 [0%] in group 2). CONCLUSIONS: Augmentation of ST segment elevation during recovery from exercise testing was specific in patients with BrS, and can be a predictor of poor prognosis, especially for patients with syncope alone and for asymptomatic patients. PMID- 21029875 TI - Risk of sudden death in asymptomatic Brugada syndrome: not as high as we thought and not as low as we wished...but the contrary. PMID- 21029876 TI - Outcome of intra-atrial re-entrant tachycardia catheter ablation in adults with congenital heart disease: negative impact of age and complex atrial surgery. AB - OBJECTIVES: The aim of this study was to determine the acute and long-term outcome of radiofrequency catheter ablation (RFCA) for intra-atrial re-entrant tachycardia (IART) in adults with congenital heart disease (CHD), and predictors of these outcomes. BACKGROUND: Atrial myopathy can be progressive in CHD and contributes to the substrate for IART. Although the outcome of RFCA for IART has been well described in children and adolescents with CHD, it is unclear whether these results are similar in the adult population. METHODS: Clinical records of adults with CHD undergoing attempted RFCA of IART were analyzed retrospectively. Multivariate analyses identified clinical and procedural factors that predicted acute and long-term outcomes. RESULTS: A total of 193 procedures was performed in 130 patients (mean age 40 +/- 13 years); 82 of 118 (69%) initially attempted RFCA were successful, defined as termination of all IART circuits. The use of electroanatomic mapping was associated with a successful RFCA, whereas Fontan palliation and Mustard repair were associated with an unsuccessful RFCA. Median clinical follow-up of 77 patients (>=2 months of follow-up) after a successful RFCA was 3.7 years (range 0.2 to 10.2 years). IART recurrence was noted in 48%, cardioversion/reablation in 42%, and death in 4%. Older age and Fontan palliation were independent predictors of IART recurrence. CONCLUSIONS: In adults with CHD, acute and long-term outcomes of RFCA for IART are similar to those reported for younger cohorts. Complex atrial surgery limits the success of RFCA, and older age is associated with a higher risk of IART recurrence. PMID- 21029877 TI - A heart with 67 stents. PMID- 21029878 TI - President's page: cardiovascular professionals: are we knights in shining armor or just knaves and pawns? PMID- 21029879 TI - Conservative, true selective invasive, and routine invasive strategies in non-ST segment elevation acute coronary syndromes. PMID- 21029881 TI - Electrocardiographic differential diagnosis between Takotsubo syndrome and distal occlusion of LAD is not easy. PMID- 21029883 TI - Phakic intraocular lenses. PMID- 21029884 TI - Effects of femtosecond laser-assisted multilayer intrastromal ablation in the midperipheral cornea. AB - We describe the femtosecond laser-assisted midperipheral multilayer intrastromal ablation technique, which combines the benefit of radial keratotomy, ie, not disturbing the optical zone, with currently available technology to correct myopia. The technique was performed in 2 patients, both of whom experienced a decrease in mean corneal power. In 1 patient, the manifest refraction improved, with a 1-line increase in uncorrected visual acuity 1 day postoperatively. The multilayer intrastromal ablation technique, which flattens the cornea and decreases corneal power, can be used to correct moderate myopia without injuring the corneal epithelium. PMID- 21029885 TI - Portable photo system for Haag-Streit-type slitlamps. AB - A new camera system is described that, when attached to an existing Haag-Streit type slitlamp, can provide the photographic needs of the general ophthalmologist or optometrist conveniently and at relatively low cost. It can also be used to economically expand photography in a teaching environment. This photographic documentation is particularly beneficial when integrated into an electronic health record. PMID- 21029886 TI - Apodized diffractive intraocular lens implantation after laser in situ keratomileusis with or without subsequent excimer laser enhancement. AB - PURPOSE: To evaluate the long-term refractive and visual outcomes of apodized diffractive multifocal intraocular lens (IOL) implantation after myopic laser in situ keratomileusis (LASIK) with or without subsequent excimer laser enhancement. SETTING: University of Texas Southwestern Medical Center at Dallas, Texas, USA. DESIGN: Comparative case series. METHODS: This study comprised consecutive patients who had implantation of an AcrySof ReSTOR multifocal IOL after previous LASIK. Included were eyes that had refractive surgery enhancement with a Visx Star S4 excimer laser for residual refractive error correction and eyes that had neodymium:YAG (Nd:YAG) capsulotomy. RESULTS: Of the 49 eyes (38 patients), 21 (42.9%) had laser enhancement and 25 (51.0%) had an Nd:YAG capsulotomy. The mean follow-up was 14.2 months +/- 7.23 (SD) (range 9 to 29 months). Although the uncorrected distance visual acuity (UDVA) was significantly worse in eyes with enhancement than in those with no enhancement at 1 month and 6 months (P<.05), there was no significant difference in UDVA between the 2 groups at the last follow-up (P>.05). At the last follow-up, 36 (73.5%) of the 49 eyes had a UDVA of 20/25 or better and an uncorrected near visual acuity of Jaeger 1 or better concurrently; 46 eyes (93.9%) were within +/-1.00 diopter (D) of emmetropia, and 41 (83.7%) were within +/-0.50 D. CONCLUSION: Apodized diffractive multifocal IOL implantation and excimer laser enhancement in eyes with previous myopic LASIK provided good results. PMID- 21029887 TI - Corneal biomechanical characteristics in patients with diabetes mellitus. AB - PURPOSE: To compare the corneal biomechanical properties in eyes of patients with diabetes mellitus and in those of subjects without diabetes mellitus. SETTING: Hospital eye clinic. DESIGN: Comparative case series. METHODS: Corneal hysteresis (CH) and corneal response factor (CRF) were measured in diabetic patients and nondiabetic subjects using the Ocular Response Analyzer. Central corneal thickness (CCT) and intraocular pressure (IOP) were also measured. Differences in corneal biomechanical properties were determined using a 1-way analysis of variance. Interassociations between ocular and diabetic parameters were also evaluated. RESULTS: Sixty-one eyes of 61 diabetic patients and 123 eyes of 123 nondiabetic subjects were evaluated. The CRF was significantly greater in the eyes of diabetic patients (mean difference, 1.09 mm Hg; 95% confidence interval [CI], 0.49-1.69; P = .001). There were no significant differences in CCT or CH between groups (CH: mean difference, 0.38 mm Hg; 95% CI, -0.21 to 0.97 mm Hg; P = .21; CCT: mean difference, 0.13 MUm; 95% CI, -10.6 to 10.8 MUm; P =.98). Corneal hysteresis and CRF were weakly correlated with blood glucose concentration (slopes: CH: 0.28; 95% CI, 0.03-0.50; P = .03; CRF: 0.27; 95% CI 0.02-0.49; P = .04). In a multiple regression analysis, the effects of blood glucose concentration were reduced and age and CCT became significant predictors of CH and CRF. CONCLUSIONS: The eyes in diabetic patients displayed altered corneal biomechanics that may be related to blood glucose concentration. Further studies are required to establish the effects of long-term poor glucose control on corneal biomechanical properties and how this might affect the diabetic patient's response to refractive surgery procedures. PMID- 21029888 TI - Improving the prediction accuracy of the SRK/T formula: the T2 formula. AB - PURPOSE: To investigate the causes of nonphysiologic behavior of the SRK/T formula, assess their clinical significance, and develop and evaluate solutions. SETTING: Two NHS ophthalmology departments, United Kingdom, and a private practice, United States. DESIGN: Evaluation of technology. METHODS: The individual steps of the SRK/T formula were examined for nonphysiologic behavior, and the clinical significance of behaviors was assessed with reference to a database of biometry and refractive outcomes in 11 189 eyes. The full data set was divided into 2 subsets, the first to develop solutions to nonphysiologic behavior of the SRK/T formula and the second to evaluate their performance. RESULTS: The SRK/T formula showed nonphysiologic behavior in the calculation of corrected axial length and corneal height. Although the former is of little clinical significance, the latter showed a systematic error that contributes to inaccurate intraocular lens (IOL) power prediction. The T2 formula was developed using a regression formula for corneal height derived from the development subset. Comparison of the performance of the T2 and SRK/T formulas using the evaluation subset showed significant improvement in the mean absolute error with the T2 formula (0.3064 diopter [D] versus 0.3229 D; P<.0001). On average, the prediction error with the T2 formula was 9.7% less than with the SRK/T formula, with significantly higher proportions of eyes within +/-0.50 D of target (P<.0001). CONCLUSIONS: The SRK/T formula has nonphysiologic behavior that contributes to IOL power prediction errors. A modification to the formula algorithm, the T2 formula, can be directly substituted for SRK/T, resulting in significantly improved prediction accuracy. PMID- 21029889 TI - Construct validity of a surgical simulator as a valid model for capsulorhexis training. AB - PURPOSE: To compare the performance on the EYESi surgical simulator capsulorhexis training module between medical students and residents and experienced cataract surgeons. SETTING: Department of Ophthalmology, University of Iowa, Iowa City, Iowa, USA. DESIGN: Comparative case series. METHODS: The study comprised medical students and residents at the University of Iowa and experienced cataract surgeons. Neither group had experience with the simulator. Each participant completed 4 trials on the capsulorhexis module. RESULTS: The 7 experienced surgeons achieved statistically significantly better total scores than the 16 medical students and residents on the easy level and the medium level of the capsulorhexis module (P = .004 and P = .000007, respectively). Experienced surgeons achieved significantly better scores in all parameters at the medium level, with better centering (P = .001), less corneal injury (P = .02), fewer spikes (P = .03), less time operating without a red reflex (P = .0005), better roundness of the capsulorhexis (P = .003), and less time completing tasks (P = .008). CONCLUSION: The surgical simulator capsulorhexis module showed significant construct validity (P<.05). PMID- 21029890 TI - Adherent ocular bandage for clear corneal incisions used in cataract surgery. AB - PURPOSE: To assess an adherent ocular bandage for clear corneal incisions (CCIs) in cataract surgery using optical coherence tomography (OCT). SETTING: Prince Charles Eye Unit, Windsor, United Kingdom. DESIGN: Case-control study. METHODS: Patients having coaxial microincision cataract surgery (MICS) were allocated to an adherent ocular bandage group or to a control group. The CCIs were examined postoperatively within 2 hours and at 24 hours and 7 days using OCT imaging and a slitlamp fluorescein 2% Seidel test. RESULTS: The ocular bandage group comprised 22 eyes and the control group, 23 eyes. The mean intraocular pressure (IOP) in the immediate postoperative period was significantly lower in the control group (13.4 mm Hg +/- 5.28 [SD]; range 5 to 23 mm Hg) than in the bandage group (19.4 +/- 5.94 mm Hg, range 11 to 29 mm Hg) (P<.001, t test). In the bandage group, all incisions were Seidel negative. In the control group, 1 main incision was Seidel positive. In 2 cases, the bandage successfully captured a micro-leak and thus maintained an intact anterior chamber. Differences in OCT architectural features between the bandage group and control group were noted. CONCLUSIONS: The adherent ocular bandage protected the incisions, selectively adhering to deepithelialized areas and rapidly clearing from reepithelialized areas. The bandage helped maintain a more desirable IOP in the immediate postoperative period, likely by preventing micro-leaks. PMID- 21029891 TI - Phacoemulsification versus manual small-incision cataract surgery for white cataract. AB - PURPOSE: To compare the safety and efficacy of phacoemulsification and manual small-incision cataract surgery (SICS) to treat white cataracts in southern India. SETTING: Aravind Eye Hospital, Pondicherry, India. DESIGN: Randomized prospective study. METHODS: Consecutive patients with white cataract were randomly assigned to have phacoemulsification or manual SICS by 1 of 3 surgeons experienced in both techniques. Surgical complications, operative time, uncorrected (UDVA) and corrected (CDVA) distance visual acuities, and surgically induced astigmatism were compared. RESULTS: On the first postoperative day, the UDVA was comparable in the 2 groups (P = .805) and the manual SICS group had less corneal edema (10.2%) than the phacoemulsification group (18.7%) (P = .047). At 6 weeks, the UDVA was 20/60 or better in 99 patients (87.6%) in the phacoemulsification group and 96 patients (82.0%) in the manual SICS group (P = .10) and the CDVA was 20/60 or better in 112 (99.0%) and 115 (98.2%), respectively (P = .59). The mean time was statistically significantly shorter in the manual SICS group (8.8 minutes +/- 3.4 [SD]) than in the phacoemulsification group (12.2 +/- 4.6 minutes) (P<.001). Posterior capsule rupture occurred in 3 eyes (2.2%) in the phacoemulsification group and 2 eyes (1.4%) in the manual SICS group (P = .681). CONCLUSIONS: Both techniques achieved excellent visual outcomes with low complication rates. Because manual SICS is significantly faster, less expensive, and less technology-dependent than phacoemulsification, it may be a more appropriate technique in eyes with mature cataract in the developing world. PMID- 21029892 TI - Comparison of endothelial changes and power settings between torsional and longitudinal phacoemulsification. AB - PURPOSE: To compare the intraoperative and postoperative outcomes of conventional longitudinal phacoemulsification and torsional phacoemulsification. SETTING: Department of Ophthalmology, University of Leipzig, Germany. DESIGN: Randomized single-center clinical trial. METHODS: Eyes with senile cataract were randomized to have phacoemulsification using the Infiniti Vision System and the torsional mode (OZil) or conventional longitudinal mode. Primary outcomes were corrected distance visual acuity (CDVA) and central endothelial cell density (ECD), calculated according to the Conference on Harmonisation-E9 Guidelines in which missing values were substituted by the median in each group (primary analysis) and the loss was then calculated using actual data (secondary analysis). Secondary outcomes were ultrasound (US) time, cumulative dissipated energy (CDE), and percentage total equivalent power in position 3. Postoperative follow-up was at 3 months. RESULTS: The mean preoperative CDVA was 0.41 logMAR in the torsional group and 0.38 logMAR in the longitudinal group, improving to 0.07 logMAR postoperatively in both groups. The mean ECD loss was 7.2% +/- 4.6% in the torsional group (72 patients) and 7.1% +/- 4.4% in the longitudinal group (76 patients), with no statistically significant differences in the primary analysis (P = .342) or secondary analysis (P = .906). The mean US time, CDE, and percentage total equivalent power in position 3 were statistically significantly lower in the torsional group (98 patients) than in the longitudinal group (94 patients) (P<.001). CONCLUSION: The torsional mode was as safe as the longitudinal mode in phacoemulsification for age-related cataract. PMID- 21029893 TI - Comparative analysis of white-to-white and angle-to-angle distance measurements with partial coherence interferometry and optical coherence tomography. AB - PURPOSE: To perform white-to-white (WTW) and angle-to-angle (ATA) distance measurements with 2 optical devices and analyze the correlation with other anterior segment parameters. SETTING: Department of Ophthalmology, Medical Health and Science Center, University of Debrecen, Debrecen, Hungary. DESIGN: Comparative case series. METHODS: In this prospective study, the WTW distance, axial length (AL), and anterior chamber depth (ACD) were measured by partial coherence interferometry (PCI) (IOLMaster). The horizontal and vertical ATA distances and ACD were assessed by anterior segment optical coherence tomography (AS-OCT) (Visante). RESULTS: The mean PCI values were AL, 23.31 mm +/- 1.52 (SD); WTW distance, 11.99 +/- 0.47 mm; ACD, 2.99 +/- 0.4 mm. On AS-OCT, the mean horizontal ATA was 11.43 +/- 0.51 mm and the mean vertical ATA, 10.72 +/- 0.66 mm. The WTW distance was significantly greater than the horizontal ATA distance, and the horizontal ATA distance was significantly greater than the vertical ATA distance (P<.0001). The correlations between WTW and horizontal ATA (r = 0.51; P<.0001), vertical ATA (r = 0.32; P<.0021), AL (r = 0.45; P<.0001), and patient age (r = -0.28; P = .023) were significant. The PCI WTW distance and ACD were significantly correlated (r = 0.55; P<.0001). There were no significant correlations between AS-OCT horizontal and vertical ATA measurements (r = -0.02; P = 0.79) or between same-device ACD measurements (r = 0.18; P = .15). CONCLUSIONS: Although PCI WTW and AS-OCT ATA measurements are not clinically interchangeable, the WTW values correlated well with horizontal and vertical measurements and other anterior segment parameters. PMID- 21029894 TI - Repeatability and reproducibility of anterior ocular biometric measurements with 2-dimensional and 3-dimensional optical coherence tomography. AB - PURPOSE: To evaluate the repeatability and reproducibility of central corneal thickness (CCT), anterior chamber depth (ACD), and anterior chamber width (ACW) measurements using 3-dimensional (3-D) corneal and anterior segment optical coherence tomography (CAS-OCT) and 2-dimensional (2-D) anterior segment OCT (AS OCT). SETTING: Department of Ophthalmology, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan. DESIGN: Nonrandomized clinical trial. METHODS: The CCT, ACD, and ACW were measured in normal eyes using a prototype 3-D swept-source CAS-OCT device and a 2-D time-domain AS-OCT device (Visante). The coefficient of repeatability and reproducibility and the intraclass correlation coefficient (ICC) were calculated to evaluate the repeatability and reproducibility of the measurements. RESULTS: Eighty-five eyes (85 subjects) were evaluated. The mean CCT measurement was 557.5 MUm +/- 40.5 (SD) with CAS-OCT and 556.4 +/- 39.4 MUm with AS-OCT; the mean ACD measurement, 3.13 +/- 0.40 mm and 3.16 +/- 0.39 mm, respectively; and the mean ACW, 11.80 +/- 0.47 mm and 11.79 +/- 0.49 mm, respectively. There was no statistically significant difference in CCT or ACW measurements between the 2 devices (P>.05, Wilcoxon signed rank test). Although the ACD measurements were significantly different (P<.0001), the difference was small (0.03 mm). Significant linear correlations were found between the measurements of the 2 devices (P<.0001). The ICC was greater than 0.99 for CAS-OCT and greater than 0.96 for AS-OCT. CONCLUSION: Corneal and anterior segment OCT and AS-OCT provided comparable and well-correlated anterior ocular biometric measurements, with sufficient repeatability and reproducibility. PMID- 21029895 TI - Comparison of reading performance after bilateral implantation of multifocal intraocular lenses with +3.00 or +4.00 diopter addition. AB - PURPOSE: To compare reading ability after cataract surgery and bilateral implantation of multifocal intraocular lenses (IOLs) with a +3.00 diopter (D) addition (add) or a +4.00 D add. SETTING: Department of Ophthalmology, University of Sao Paulo, Sao Paulo, Brazil. DESIGN: Prospective comparative study. METHODS: Patients scheduled for cataract surgery were randomly assigned to bilateral implantation of an aspheric AcrySof ReSTOR multifocal IOL with a +3.00 diopter (D) addition (add) or a +4.00 D add. The reading speed, critical print size, and reading acuity were measured binocularly with best correction using MNREAD acuity charts 6 months after surgery. Patients were tested with the chart at the best patient-preferred reading distance and at 40 cm. Binocular uncorrected and best distance-corrected visual acuities at far and near were also measured. RESULTS: The study enrolled 32 patients. At the best reading distance, the results were similar between the 2 IOL groups in all reading parameters. When tested at 40 cm, reading speed at all print sizes from 0.3 to 0.0 (all P<.001), critical print size (P<.001), and reading acuity (P = .014) were statistically significantly better in the +3.00 D IOL group than in the +4.00 D IOL group. Uncorrected and corrected visual acuities at far and near were similar between the 2 groups. CONCLUSION: Although the 2 IOL groups had similar performance in reading parameters, patients had to adjust to their best reading distance. The +3.00 D IOL performed better than the +4.00 D IOL at 40 cm. PMID- 21029896 TI - Long-term reading performance in patients with bilateral dual-optic accommodating intraocular lenses. AB - PURPOSE: To evaluate reading ability in patients who had cataract surgery with binocular implantation of a dual-optic accommodating intraocular lens (IOL) over a 2-year period. SETTING: Department of Ophthalmology, Cataract and Refractive Surgery, Salucoop EPS-ServiOftalmos, Bogota, Colombia. DESIGN: Prospective case series. METHODS: This study assessed reading ability 1 year and 2 years after bilateral implantation of the Synchrony IOL accommodating IOL using standardized Spanish reading charts based on MNRead charts. Testing was performed with distance correction and without near addition (40 cm). Patients read aloud sentences with a print size ranging from 1.0 to 0.0 logMAR. Responses were audio taped and analyzed offline to obtain reading speed (words per minute [wpm]), reading acuity (logMAR), and critical print size (logMAR). RESULTS: Mixed-model analysis of variance with time (1 year and 2 years) and print size (1.0 to 0.0 logMAR; 11 levels) as factors showed statistically significantly better reading speed at 2 years, with significant differences at print sizes from 0.3 to 0.1 logMAR (P<.01). Mean reading acuity (0.07 logMAR versus 0.15 logMAR) (P<.01, paired t test) and critical print size (0.28 logMAR versus 0.48 logMAR) were also statistically significantly better at 2 years than at 1 year (both P<.01, paired t test). There was no significant difference in reading speed at 0.4 logMAR (newspaper print or 20/50 Snellen equivalent) between 1 year (180.5 wpm) and 2 years (184.2 wpm) (P = .90, paired t test). CONCLUSION: The dual-optic accommodating IOL provided stable or improved reading ability over a 2-year period. PMID- 21029897 TI - Improvements in patient-reported outcomes and visual acuity after bilateral implantation of multifocal intraocular lenses with +3.0 diopter addition: multicenter clinical trial. AB - PURPOSE: To assess changes in patient-reported outcomes, satisfaction, vision quality, and visual acuity after bilateral implantation of multifocal intraocular lenses (IOLs) with a 3.00 D addition (add) in cataract patients. SETTING: Twelve study centers, United States. DESIGN: Randomized multicenter clinical trial. METHODS: In this 6-month trial, cataract patients had bilateral implantation of the AcrySof IQ ReSTOR +3.0 IOL (model SN6AD1). Patient-reported outcomes were collected using the Cataract TyPE questionnaire. Clinical outcomes included uncorrected near (UNVA), uncorrected intermediate (UIVA), and uncorrected distance (UDVA) visual acuities. RESULTS: The study comprised 147 patients. From preoperatively to 6 months postoperatively, the mean UDVA improved from 0.45 logMAR (approximate Snellen, 20/56) to 0.04 logMAR (20/22 Snellen), the mean UIVA from 0.56 logMAR (20/73) to 0.17 logMAR (20/30), and the mean UNVA from 0.62 logMAR (20/83) to 0.10 logMAR (20/25); all improvements were clinically and statistically significant (P<.0001). There was also a statistically significant improvement in patient satisfaction with uncorrected vision (P<.0001). Clinically and statistical significant reductions occurred in trouble with vision (daytime and nighttime), trouble with glare, limitations with UDVA, limitations with UNVA, and limitations in social activities (P<.0001). CONCLUSIONS: Bilateral implantation of multifocal intraocular lenses (IOLs) with a 3.00 D add produced statistically significant and clinically relevant postoperative improvements in UNVA, UIVA, and UDVA. Commensurate significant postoperative improvements were observed in the patient-reported uncorrected functional vision, satisfaction with uncorrected vision, and social activities. PMID- 21029898 TI - Visual outcome and patient satisfaction after multifocal intraocular lens implantation: aspheric versus spherical design. AB - PURPOSE: To evaluate visual outcomes and patient satisfaction after implantation of an aspheric apodized diffractive intraocular lens (IOL) or a spherical apodized diffractive IOL in cataract surgery. SETTING: Maastricht University Medical Center, The Netherlands. DESIGN: Nonrandomized clinical trial. METHODS: This prospective nonrandomized study with a 6-month follow-up compared the results of cataract surgery with implantation of an aspheric AcrySof ReSTOR SN6AD3 IOL and a spherical AcrySof ReSTOR SN60D3 IOL. Main outcome measures were uncorrected (UDVA) and corrected (CDVA) distance visual acuities, uncorrected (UNVA) and distance-corrected (DCNVA) near visual acuities, straylight levels, incidence of glare and halos, and contrast sensitivity levels. RESULTS: The mean UDVA was 0.14 +/- 0.15 logMAR in the aspheric group (47 eyes) and 0.14 logMAR +/- 0.17 (SD) in the spherical group (45 eyes) and the mean CDVA, -0.01 +/- 0.06 logMAR and 0.02 +/- 0.10 logMAR, respectively. The mean UNVA was Jaeger (J) 1 in 83.0% of patients in the aspheric group and 55.5% of patients in the spherical IOL group (P = .003). The DCNVA was J1 in 95.7% and 71.1%, respectively (P = .001). There were no significant differences between the 2 groups in contrast sensitivity levels, intraocular straylight levels, incidence of night-vision symptoms, or subjective rating of vision. CONCLUSIONS: Patients with the aspheric multifocal IOL had significantly better near vision than patients with the multifocal spherical IOL. The UDVA, CDVA, intraocular straylight, night-vision symptoms, and contrast sensitivity were similar between the 2 groups. PMID- 21029899 TI - Aspheric microincision intraocular lens implantation with biaxial microincision cataract surgery: efficacy and reliability. AB - PURPOSE: To evaluate the efficacy and reliability of a microincision intraocular lens (IOL) and its use in biaxial microincision cataract surgery (MICS). SETTING: Ataturk Training and Research Hospital, Ankara, Turkey. DESIGN: Prospective clinical study. METHODS: A microincision IOL (Akreos MI60) was implanted after cataract extraction by the biaxial MICS technique. Over a postoperative follow-up of 12 months or more, visual acuity, contrast sensitivity, surgically induced astigmatism (SIA), corneal and ocular aberrations, and early and late complications were recorded. RESULTS: The IOLs were implanted in the capsular bag in all 100 eyes. The mean final incision size was 1.82 mm +/- 0.09 (SD). Postoperatively, the mean corrected distance visual acuity was 0.06 +/- 0.10 logMAR; the mean spherical equivalent, -0.48 +/- 0.91 diopter (D); and the mean calculated SIA, 0.20 +/- 0.22 D. Contrast sensitivity with and without glare was within normal limits. There was no statistically significant difference in the root mean square of total corneal aberrations between preoperatively and postoperatively. Ocular wavefront analysis 3 months postoperatively showed mean values of 0.15 +/- 0.2 MUm for spherical aberration, 0.38 +/- 0.16 MUm for higher order aberrations, 0.18 +/- 0.14 MUm for coma, and 0.14 +/- 0.08 MUm for trefoil. The 4 cases (4.0%) of membranous anterior chamber reaction resolved with treatment. None of the 20 eyes (20.0%) with posterior capsule opacification required neodymium:YAG capsulotomy. All IOLs remained well centered. CONCLUSION: The aspheric microincision IOL was safely implanted through a 1.8 mm or smaller incision during biaxial MICS and gave good postoperative outcomes. PMID- 21029900 TI - Incidence of diffuse lamellar keratitis after LASIK with 15 KHz, 30 KHz, and 60 KHz femtosecond laser flap creation. AB - PURPOSE: To compare the incidence of diffuse lamellar keratitis (DLK) after laser in situ keratomileusis (LASIK) with flap creation using the 15 kHz (FS15), 30 kHz (FS30), or 60 kHz (FS60) femtosecond laser. SETTING: University-based academic practice, Ann Arbor, Michigan, USA. DESIGN: Retrospective comparative case series. METHODS: Consecutive myopic LASIK cases performed between January 1, 2005, and June 1, 2007, using the IntraLase FS15, FS30, or FS60 femtosecond laser for flap creation were reviewed. Preoperative clinical characteristics, treatment parameters, and intraoperative and postoperative complications were recorded. Statistical comparisons were made using repeated measures analysis, analysis of variance, chi-square, and Fisher exact tests. RESULTS: Five hundred twenty eyes of 274 patients were included in the study. One hundred seventy-six eyes (93 patients) were treated with the FS15 laser, 180 eyes (93 patients) with the FS30 laser, and 164 eyes (89 patients) with the FS60 laser. Seventeen eyes (10%) in the FS15 laser group, 24 eyes (13%) in the FS30 laser group, and 23 eyes (14%) in the FS60 laser group developed DLK. There was no statistically significant difference in the incidence of DLK between the 3 groups (P = .68). CONCLUSION: There was no significant difference in the incidence of DLK between the FS15, FS30, and FS60 groups. PMID- 21029901 TI - Straylight before and after hyperopic laser in situ keratomileusis or laser assisted subepithelial keratectomy. AB - PURPOSE: To compare straylight values before and 3 months after hyperopic laser in situ keratomileusis (LASIK) or laser-assisted subepithelial keratectomy (LASEK) and determine the cause of any change. SETTING: Private refractive surgery clinic, Driebergen, The Netherlands. DESIGN: Comparative case series. METHODS: Straylight (by definition the measure for glare disability) was measured preoperatively and postoperatively with a C-Quant straylight meter and recorded as log(s). The main outcome measures were the difference between postoperative and preoperative straylight values. RESULTS: The mean increase in straylight from preoperatively to postoperatively was 0.051 log(s) +/- 0.158 (SD) in the LASIK group (39 eyes) and 0.031 +/- 0.146 log(s) in the LASEK group (26 eyes). Although neither change was statistically significant, it was clinically significant in some cases. Haze or interface debris was seen in some eyes with increased straylight. The mean postoperative spherical equivalent refraction was -0.05 +/- 0.27 diopter. CONCLUSIONS: Although straylight increased slightly after hyperopic LASIK and LASEK, the increase was not statistically significant. Some eyes with increased straylight had haze or interface debris. The cause of the increased straylight could not be determined in some cases. PMID- 21029902 TI - Laser in situ keratomileusis flap complications using mechanical microkeratome versus femtosecond laser: retrospective comparison. AB - PURPOSE: To compare the incidence of flap complications after creation of laser in situ keratomileusis (LASIK) flaps using a zero-compression microkeratome or a femtosecond laser. SETTING: John A. Moran Eye Center, Department of Ophthalmology, University of Utah, Salt Lake City, Utah, USA. DESIGN: Evidence based manuscript. METHODS: The flap complication rate was evaluated during the initial 18 months of experience using a zero-compression microkeratome (Hansatome) or a femtosecond laser (IntraLase FS60) for flap creation. RESULTS: The flap complication rate was 14.2% in the microkeratome group and 15.2% in the femtosecond laser group (P = .5437). The intraoperative flap complication rate was 5.3% and 2.9%, respectively (P = .0111), and the postoperative flap complication rate, 8.9% and 12.3%, respectively (P = .0201). The most common intraoperative complication in the microkeratome group was major epithelial defect/sloughing; the rate (2.6%) was statistically significantly higher than in the femtosecond laser group (P = .0006). The most common postoperative complication in both groups was diffuse lamellar keratitis (DLK) (6.0%, microkeratome; 10.6%, femtosecond laser) (P = .0002). CONCLUSION: Although the total complication rates between the 2 groups were similar, the microkeratome group had significantly more epithelial defects intraoperatively and the femtosecond laser group had significantly more DLK cases postoperatively. PMID- 21029903 TI - Long-term comparison of corneal aberration changes after laser in situ keratomileusis: mechanical microkeratome versus femtosecond laser flap creation. AB - PURPOSE: To compute and compare visual acuity, refractive outcomes, and anterior corneal aberration changes after myopic laser in situ keratomileusis (LASIK) with flap creation by a mechanical microkeratome and by a femtosecond laser. SETTING: Private practice refractive surgery center, Valencia, Spain. DESIGN: Comparative case series. METHODS: Patients were assigned to have LASIK flap creation with a mechanical microkeratome (Carriazo-Barraquer) or a femtosecond laser (IntraLase). The Visx S2 excimer laser was used for myopic ablation in all cases. Main outcome measures included uncorrected and corrected distance visual acuities and the defocus equivalent. Higher-order aberrations (HOAs) were computed from the anterior corneal surface measured with topography for 4.0 mm and 6.0 mm pupil diameters before and 48 months after surgery. RESULTS: The study evaluated 50 patients (98 eyes). The root mean square of HOAs increased postoperatively by a factor of approximately 1.9 in both groups and with both pupil diameters. There were no statistically significant differences between the 2 groups in the increase in anterior corneal aberrations, mean postoperative visual acuity, or residual refraction. All visual and optical performance metrics remained stable throughout the 4-year follow-up. There were no complications with flap creation and no postoperative complications. CONCLUSIONS: The increase in anterior corneal aberrations after myopic LASIK was similar after mechanical microkeratome and femtosecond laser flap creation. Visual acuity, refraction, and the optical quality of the cornea after LASIK remained stable through 4 years postoperatively in both groups. PMID- 21029904 TI - Effect of laser in situ keratomileusis on vision analyzed using preoperative optical quality. AB - PURPOSE: To evaluate the effect on vision of laser in situ keratomileusis (LASIK) based on preoperative optical quality. SETTING: Universitat Politecnica de Catalunya, Terrassa, and Barcelona Institute of Ocular Microsurgery, Barcelona, Spain. DESIGN: Comparative case series. METHODS: The relative change in optical quality and visual acuity were evaluated in eyes that had LASIK for myopia. The optical quality was assessed before and 3 months after surgery using parameters provided by a double-pass system. Patients were classified into 4 groups by preoperative optical quality: low (Group 1), moderate (Group 2), high (Group 3), and very high (Group 4). RESULTS: The study evaluated 25 patients (50 eyes). The optical quality parameters improved postoperatively in Group 1 and Group 2, with the improvement ranging from 15% to 21% and from 13% to 17%, respectively. The preoperative and postoperative optical quality in Group 3 was similar. The optical quality in Group 4 worsened significantly by percentages ranging from 20% to -26%. Although visual acuity had the same trend, there were no statistically significant changes. CONCLUSION: The changes in optical quality after LASIK surgery depended on the patient's preoperative optical quality; visual acuity showed the same trend, although no change was significant. PMID- 21029905 TI - Mechanized model to assess capsulorhexis resistance to tearing. AB - PURPOSE: To evaluate a model of mechanically measuring resistance to tearing of a continuous curvilinear capsulorhexis (CCC) using the entire capsular bag of fresh human cadaver eyes isolated from the eyes after complete evacuation. SETTING: John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, USA. DESIGN: Experimental study. METHODS: After the cornea and iris were removed, a 5.0 to 5.5 mm anterior CCC was created. The nucleus was hydroexpressed and the capsular bag evacuated by irrigation/aspiration. A pair of metal shoetree-shaped fixtures, designed based on human lens geometric dimensions, were implanted separately in the capsular bag and assembled together with a screw nut. After complete zonulectomy, the fixture-capsular bag assembly was removed from the eye and loaded onto a mechanical tester. The fixtures were separated at a velocity of 7.0 mm/min in 0.15 MUm intervals to stretch the CCC to its rupture point. Rupture load (N) and extension were measured and graphed. RESULTS: Testing of 23 donor eyes a mean of 69.04 hours +/- 22.72 (SD) after death showed the following mean values: CCC diameter, 5.3 +/- 0.12 mm; load, 0.39 +/- 0.16 N; extension at CCC tearing, 5.85 +/- 1.17 mm. There was a moderately strong negative correlation between donor age and load (P = .0018). CONCLUSIONS: Previous mechanized methods of assessing CCC strength used excised anterior capsules or partially phacoemulsified crystalline lenses, yielding lower tension strength values. This force-displacement method may facilitate assessment of small differences between anterior capsulotomy techniques. PMID- 21029906 TI - Model of accommodation: contributions of lens geometry and mechanical properties to the development of presbyopia. AB - PURPOSE: To determine the relative importance of lens geometry and mechanical properties for the mechanics of accommodation and the role of these elements in the causes and potential correction of presbyopia. SETTING: Department of Mechanical and Aerospace Engineering, Princeton University, Princeton, New Jersey, USA. DESIGN: Experimental study. METHODS: Finite element methods and ray tracing algorithms were used to model the deformation and optical power of the human crystalline lens during accommodation. The mechanical model treats the lens as an axisymmetric object, and the optical model incorporates a gradient refractive index. Using these models, the accommodation of a broad range of lenses with different geometries and mechanical properties were investigated. RESULTS: The most significant result was that reshaping the 45-year-old lens to the geometry of the 29-year-old lens, while retaining the mechanical properties, restored the former's accommodation amplitude to 72% to 94% of that of the 29 year-old lens, depending on ciliary body displacement. That is, reshaping can add 1.8 to 3.7 diopters of accommodation. A sensitivity analysis showed that this result was robust over a wide range of mechanical and geometrical properties. CONCLUSION: The study results suggest that a significant amount of the loss of accommodation is due to changes in lens geometry. PMID- 21029907 TI - Protective effect of different ophthalmic viscosurgical devices on corneal endothelial cells during phacoemulsification: rabbit model. AB - PURPOSE: To evaluate the protective effect of different ophthalmic viscosurgical devices on corneal endothelial cells during phacoemulsification in a rabbit model. SETTING: Harlan Biotech Israel and Ophthalmology Department, Kaplan Medical Center, Rehovot, Israel. DESIGN: Experimental study. METHODS: Rabbit eyes were randomly assigned to 3 equally sized groups. Endothelial cell counts were performed in all eyes before initiation of the study. The aqueous humor was completely replaced by Biolon (sodium hyaluronate 1.0%) in Group A, by a combination of Viscoat (sodium chondroitin sulfate 4.0%-sodium hyaluronate 3.0%) and Provisc (sodium chondroitin sulfate 1.0%) using the soft-shell technique in Group B, and by a combination of Visiol (sodium hyaluronate 2.0%-mannitol 0.5%) and Biolon using the soft-shell technique in Group C. The eyes were exposed to alternating 10 seconds of phacoemulsification and a 10-second pause until a total exposure time of 2.5 minutes elapsed. Endothelial cell counts were repeated 3 days after surgery. RESULTS: The study used 18 rabbit eyes, 6 in each group. Group A had the highest endothelial cell loss (13%) followed by Group B (7%), and Group C (4%). The difference in cell loss between Group C and Group A was statistically significant (P = .037). CONCLUSION: The study showed the efficiency and advantages of the soft-shell technique using the combination of Visiol and Biolon over Biolon alone. PMID- 21029908 TI - Phakic intraocular lenses part 1: historical overview, current models, selection criteria, and surgical techniques. AB - In this 2-part overview, the current status of phakic intraocular lens (pIOL) surgery to correct refractive errors is reviewed. Three types of pIOLs, categorized by their intraocular position, are included: angle-supported anterior chamber, iris-fixated anterior chamber, and posterior chamber (usually fixated in the ciliary sulcus). Part 1 reviews the main models of each pIOL type, the selection criteria, and the surgical techniques, with emphasis on currently available pIOLs. Bioptics, adjustable refractive surgery, and enhancements are addressed, and applications of the new anterior segment imaging techniques are reviewed. PMID- 21029909 TI - Bilateral loss in the quality of vision associated with anterior corneal protrusion after hyperopic LASIK followed by intrastromal femtolaser-assisted incisions. AB - A patient was treated bilaterally for hyperopia (twice in the right eye and 3 times in the left eye) using laser in situ keratomileusis (LASIK) and achieved stable vision. Preoperatively, there was no known risk factor for ectasia. Three years after the last LASIK enhancement treatment, intrastromal femtolaser assisted incisions (Intracor procedure using the Technolas femtosecond laser) were made bilaterally. After the procedure, a severe loss in the corrected distance visual acuity and in the quality of vision occurred, associated with a topography pattern suggestive of isolated anterior central protrusion. This case suggests that intrastromal femtosecond incisions in eyes that have had hyperopic LASIK should be done with caution, as there is no certainty about how the treated corneas will respond. PMID- 21029911 TI - Late dislocation of intrastromal corneal ring segment into the anterior chamber. AB - We describe the case of a 53-year-old woman with keratoconus who presented with a dislocated intrastromal corneal ring segment (ICRS) (Intacs) in the anterior chamber 3 weeks after surgery. To our knowledge, this is the first report of a late occurrence of postoperative anterior chamber dislocation of an ICRS and illustrates the need to consider the potential for such a complication. PMID- 21029910 TI - Early serous macular detachment after phacoemulsification surgery. AB - We report 2 cases of serous macular detachment with intraretinal fluid accumulation that developed 1 day after uneventful phacoemulsification surgery. Because of a dilution error, both eyes received 2 mg/0.1 mL of intracameral cefuroxime at the end of surgery. On postoperative day 1, the corrected distance visual acuity (CDVA) was 20/400 in both eyes. Optical coherence tomography revealed intraretinal fluid accumulation with serous macular detachment, and central foveal thickness measurements were 909 MUm and 559 MUm in Case 1 and Case 2, respectively. Case 1 responded to systemic acetazolamide, but the condition recurred after cessation of therapy; it then responded to systemic steroid treatment. Case 2 responded to an intravitreal injection of 4 mg of triamcinolone and remained stable throughout the follow-up. The final CDVA was 20/20 in Case 1 and 20/25 in Case 2, and central foveal thickness measurements were 205 MUm and 208 MUm, respectively. PMID- 21029912 TI - What urologists know about intraoperative floppy-iris syndrome. PMID- 21029913 TI - Implications of MHRA's reclassification of tamsulosin. PMID- 21029914 TI - Intraoperative floppy iris syndrome and microincision cataract surgery. PMID- 21029915 TI - Refractive Surgical Problem November consultation #1-8. PMID- 21029923 TI - Reasons for intrastromal corneal ring segment explantation. PMID- 21029926 TI - Bilateral corneal ectasia after laser in situ keratomileusis. PMID- 21029927 TI - Is central pachymetry asymmetry between eyes an independent risk factor for ectasia after LASIK? PMID- 21029929 TI - Corneal/scleral thinning and corticosteroids. PMID- 21029930 TI - Foreword. Infection and asthma. PMID- 21029931 TI - Infectious Diseases and Asthma. Preface. PMID- 21029933 TI - Viral diversity in asthma. AB - Asthma exacerbations are precipitated primarily by respiratory virus infection and frequently require immediate medical intervention. Studies of childhood and adult asthma have implicated a wide variety of respiratory viruses in exacerbations. By focusing on both RNA and DNA respiratory viruses and some newly identified viruses, this review illustrates the diversity and highlights some of the uncertainties that exist in our understanding of virus-related asthma exacerbations. PMID- 21029932 TI - The infectious march: the complex interaction between microbes and the immune system in asthma. AB - There has been significant progress in our knowledge about the relationship between infectious disease and the immune system in relation to asthma, but many unanswered questions still remain. Respiratory tract infections such as those caused by respiratory syncytial virus and rhinovirus during the first 2 years of life are still clearly associated with later wheezing and asthma, but the mechanism has not been completely worked out. Is there an "infectious march" triggered by infection in infancy that progresses to disease pathology or are infants who contract respiratory infections predisposed to developing asthma? This review focuses on the common themes in the interaction between microbes and the immune system, and presents a critical appraisal of the evidence to date. The various mechanisms whereby microbes alter the immune response and how this might influence asthma are discussed along with new and promising clinical practices for prevention and therapy. Recent advances in using sensitive polymerase chain reaction detection methods have allowed more rigorous testing of the causality hypothesis of virus infection leading to asthma, but the evidence is still equivocal. Various exceptions and inconsistencies in the clinical trials are discussed in light of new guidelines for subject inclusion/exclusion in hopes of providing some standardization. Despite past failures in vaccination and disappointing results of some clinical trials, the new strategies for prophylaxis including RNA interference and targeted delivery of microbicides offer a large dose of hope to a world suffering from an increasing incidence of asthma as well as a huge burden of health care cost and loss of quality of life. PMID- 21029934 TI - Animal models of virus-induced chronic airway disease. AB - There is increasing evidence that experiencing viral wheezing illnesses early in life, especially in conjunction with allergic sensitization, is an important risk factor for the onset of asthma. In this review, the potential advantages and disadvantages of using rodent models of virus-induced chronic airway dysfunction to investigate the mechanisms by which early-life viral respiratory tract infections could initiate a process leading to chronic airway dysfunction and the asthmatic phenotype are discussed. The potential usefulness of rodent models for elucidating the viral, host, environmental, and developmental factors that might influence these processes is emphasized. There is a need for the continued development of rodent models of early-life viral respiratory tract infections that include the development of chronic airway dysfunction, the capacity to add components of allergic sensitization and allergic airway inflammation, and the ability to address both immunologic and physiologic consequences. Investigation of these rodent models should complement the research from pediatric cohort studies and begin to bring us closer to understanding the role of viral respiratory tract infections in the inception of childhood asthma. PMID- 21029935 TI - The role of respiratory virus infections in childhood asthma inception. AB - Viral respiratory illnesses associated with wheezing are extremely common during early life and remain a frequent cause of morbidity and hospitalization in young children. Although many children who wheeze with respiratory viruses during infancy outgrow the problem, most children with asthma and reductions in lung function at school age begin wheezing during the first several years of life. Whether symptomatic viral infections of the lower respiratory tract are causal in asthma development or simply identify predisposed children remains a controversial issue. Wheezing illnesses caused by respiratory syncytial virus (RSV), particularly those severe enough to lead to hospitalization, have historically been associated with an increased risk of asthma at school age. However, with the development of molecular diagnostics, human rhinovirus (HRV) wheezing illnesses have been recognized more recently as a stronger predictor of school-age asthma than RSV. In this article, the authors review the impact of virus infections during early life, focusing primarily on RSV and HRV, and their potential roles in asthma inception. PMID- 21029936 TI - Respiratory syncytial virus infections in the adult asthmatic--mechanisms of host susceptibility and viral subversion. AB - Respiratory syncytial virus (RSV), a single-stranded RNA virus of the Paramyxoviridae family, is a major cause of bronchiolitis in infants and is also conjectured to be an early-life influence on the development of asthma. Although the data supporting a role for RSV in bronchiolitis in children are robust and evidence to support its role in juvenile asthmatics exists, RSV's role in asthma pathogenesis in adults is not as clearly defined. The authors review the literature to further elucidate RSV's impact on adult asthmatics, including its importance as a cause of asthma exacerbations. They examine the morbidity associated with RSV infection and how the immune response may differ between adult asthmatics and nonasthmatics. They review the responses by specific cell types from adults with asthma that are stimulated by RSV. They also consider the role of early-life exposure to RSV and its contribution to asthma in adults. Lastly, they review the mechanisms by which RSV evades normal host immune responses and subverts these responses to its benefit. PMID- 21029939 TI - Bacterial infections and pediatric asthma. AB - Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis seem to have no role in asthma in children. Mycoplasma pneumoniae and Chlamydophila pneumoniae can induce wheezing and cause asthma exacerbations in children, and chronic Chlamydophila infections may even participate in asthma pathogenesis. However, studies have failed to show any benefits from antibiotics for incipient or stable pediatric asthma, as well as for asthma exacerbations in children. Exposure to antibiotics in infancy has been an independent risk factor of later asthma in many studies. A recent study applying molecular biology methods to lower airway samples provided preliminary evidence that lower airways are not sterile but have their own protective microbiota, which can be disturbed in lung diseases like asthma. PMID- 21029938 TI - Virus/allergen interactions and exacerbations of asthma. AB - Clinical research findings indicate that there are synergistic interactions between allergy and viral infection that cause increased severity of asthma exacerbations. This article summarizes the current literature linking these 2 risk factors for asthma exacerbation, and reviews experimental data suggesting potential mechanisms for interactions between viral infection and allergy that cause asthma exacerbations. In addition, the authors discuss clinical evidence that treatment of allergic inflammation could help to reduce the frequency and severity of virus-induced exacerbations of asthma. PMID- 21029937 TI - New human rhinovirus species and their significance in asthma exacerbation and airway remodeling. AB - Asthma is the most common chronic disease of childhood, affecting 10% to 15% of all children. Several different stimuli including allergens, tobacco smoke, certain drugs, and viral or bacterial infections are known to exacerbate asthma symptoms. Among these triggers, viruses are frequent inducers of asthma exacerbations, with human rhinoviruses being the most common in children and adults. This article describes the different species of this virus and their roles as major triggers of asthma exacerbations. PMID- 21029940 TI - Effects of atypical infections with Mycoplasma and Chlamydia on asthma. AB - Mycoplasma pneumoniae and Chlamydophila pneumoniae are atypical bacteria that are frequently found in patients with asthma. A definitive diagnosis of infection is often difficult to obtain because of limitations with sampling and detection. Numerous animal studies have outlined mechanisms by which these infections may promote allergic lung inflammation and airway remodeling. In addition, there is mounting evidence from human studies suggesting that atypical bacterial infections contribute to asthma exacerbations, chronic asthma, and disease severity. The role of antimicrobials directed against atypical bacteria in asthma is still under investigation. PMID- 21029941 TI - Strategies for widening liver donor pool. AB - Liver transplantation is a life-saving treatment modality, but is hindered by the scarcity of deceased-donor liver grafts. To acquire more liver grafts and thus save more lives, various techniques have been devised and policies adopted, including living-donor, split-graft and sequential liver transplantation; extended donor criteria; and donation after cardiac death. However, with these techniques and policies come a range of entailed medical concerns and concomitant ethical dilemmas, mainly bearing on the welfare of donors and potential donors. In this article, we provide an overview of how the transplant community works towards the end of extending the liver donor pool, with the aim of ensuring that more liver transplant candidates receive their transplant as early as possible. The current strategies in Hong Kong in this regard are also reviewed. PMID- 21029942 TI - Outcome of laparoscopic live donor nephrectomy and impact of double renal arteries: results from two transplant centres. AB - OBJECTIVE: Live donor kidney transplantation is consistently superior to deceased donor kidney transplantation. Laparoscopic donor nephrectomy (LDN) is increasingly accepted as a safe and preferred surgical option. To evaluate the outcome of LDN and the impact of multiple arteries, a retrospective review was conducted on patients in two transplant centres. METHODS: Fifty patients including eight with double vessels were studied. Standard left transperitoneal LDN was performed. Grafts including those with double vessels were prepared using the bench technique. Postoperative outcomes (up to 1 year) for donors and recipients were studied. The outcomes of recipients of a single or double vessel graft were compared. RESULTS: All donors had an eventful recovery. No difference was found between the single and multiple vessels groups for operating time (168.21 +/- 5.712 minutes vs. 197.50 +/- 15.755 minutes) or hospital stay (3.21+/ 0.165 days vs. 4.13+/-0.789 days). The recipient outcomes including hospital stay (10.17+/-0.596 days vs. 12.13 +/- 1.797 days) and creatinine levels at day 7 (106.53 +/- 5.583 MUmol/L vs. 107.13 +/- 11.857 MUmol/L) and 1 year (120.21 +/- 6.562 MUmol/L vs. 124.75 +/- 11.857 MUmol/L) were similar. No ureteric stricture or graft loss was noted at 1-year follow-up. Recipient complications included lymphocoele (n = 2), haematoma (n = 3 with 2 requiring exploration), sepsis (n = 1), renal artery stenosis (n = 2 with 1 stented), repeated anastomosis (n = 1), and incisional hernia (n = 1). No differences were noted between the two groups. CONCLUSION: Our results showed that overall donor morbidity rate was low, as reflected by the short hospital stay. Also, the overall parameters of the recipients were good. In particular, no ureteric stricture was noted, and graft survival was 100% at 1 year. The outcomes of the reconstructed group, despite the technical challenge, were similar to those of the single-vessel group. PMID- 21029943 TI - Predictors of invasive breast cancer in ductal carcinoma in situ initially diagnosed by core biopsy. AB - BACKGROUND: Some patients who are initially diagnosed with ductal carcinoma in situ (DCIS) by core biopsy eventually have their disease upstaged to invasive carcinoma on final excision, thus warranting some form of axillary staging. This study aimed to identify the predictors of invasive breast cancer in DCIS diagnosed by core biopsy, which could then help clinicians decide which cases of biopsy-diagnosed DCIS should undergo concurrent sentinel lymph node biopsy during excision. METHODS: The records of 95 consecutive patients diagnosed with pure DCIS from 100 core biopsies from January 2005 to August 2007 were retrospectively reviewed. The clinical, radiological and pathological characteristics of these 100 cases were correlated with the presence of invasion or microinvasion on excision. RESULTS: Factors that are associated with invasive or microinvasive foci on excisional histology are: size of target lesion on radiography >= 20 mm [odds ratio: 6.738 (1.050-43.236), p = 0.044] and <= 10 cores obtained [odds ratio: 22.343 (2.351-212.385), p = 0.007]. CONCLUSION: Underestimation of invasive breast cancer in core biopsy-diagnosed DCIS is related to the size of the lesion on radiography, as well as the number of cores obtained during biopsy. PMID- 21029944 TI - Surgery for isolated liver metastasis of ovarian cancer. AB - BACKGROUND: Few studies have been published on liver resection alone or in combination with cytoreductive surgery for liver metastases of ovarian carcinoma. METHODS: Eight patients who underwent liver resection for metastasis of ovarian cancer were included in the study. Total abdominal hysterectomy and bilateral salpingo-oophorectomy had been performed before liver surgery in all patients. The demographic data, follow-up details before and after liver resection, histopathology of the primary ovarian cancer, type of surgery and outcome were evaluated. RESULTS: The mean age of the patients was 56.1 (46-68) years. The mean hospitalization time was 8 (7-10) days. The mean disease-free interval was 5.38 years from the time of initial surgery to surgery for metastatic liver lesions, and 39 months after liver resection to secondary metastases. Four patients did not have any evidence of disease after liver surgery. CONCLUSION: Indications for liver resection should be considered in selected patients who have a limited extent of metastatic disease from ovarian carcinoma. Liver resection for metastases of ovarian carcinoma could be an effective and feasible approach. PMID- 21029945 TI - Surgical resection for patients with mucinous bronchioloalveolar carcinoma. AB - BACKGROUND: The clinical features of mucinous bronchioloalveolar carcinoma (BAC) have remained unclear due to the low incidence of this disease. This study investigated the clinicopathological features and the surgical outcome in patients with mucinous BAC. METHODS: We clinicopathologically evaluated 782 patients who underwent resection for nonsmall cell carcinoma between 1999 and 2008, of whom, 13 (1.6%) demonstrated to have mucinous BAC. RESULTS: The patients with mucinous BAC included six men and seven women. The mean age was 69.1 years (range: 55-78 years). Eight patients (61.5%) had a smoking habit. No patients had any subjective symptoms. The tumour diameter ranged from 1.2 cm to 10 cm. The surgical procedures included 11 lobectomies, and two partial resections of affected lobes. The pathological stage was IA in eight patients, IB in two, IIA in two, and IIIA in one. None of the patients had lymph node metastases or lymphovascular invasion. The overall postoperative 5-year survival rate was 52.5%. The 5-year survival rate according to tumour diameter was 100% in patients with tumours <= 3 cm, and 25.1% in patients with tumours > 3 cm. Two patients died due to pulmonary metastases, and one died from carcinomatous pleuritis and pulmonary metastases. CONCLUSION: Patients with small mucinous BAC (<= 3 cm) in diameter showed excellent prognosis after surgical resection. However, mucinous BAC > 3 cm in diameter tended to recur with pulmonary metastasis. PMID- 21029946 TI - Transillumination instrument facilitates faster and more accurate dissection of right colon segment for oesophageal reconstruction. AB - BACKGROUND: Venous insufficiency of a right colon interposition in oesophageal reconstruction can be a fatal complication. The right colon segment could allow restoration of swallowing and speech in reconstruction of the entire oesophagus. The right colon segment is a good choice because of the large middle colic artery and isoperistaltic direction. However, because of the anatomical variation of the veins and the tiny venous network of the right colon, its success rate is lower compared with that of the left colon segment. Therefore, we devised a simple instrument of transillumination that can provide an improved view during surgery of the venous network of the right colon and ileocecal region when dissecting this important structure. METHODS: Thirty-six patients underwent oesophageal reconstruction with a right colon segment using the instrument. The instrument of transillumination was used in all cases while exploring the pedicle vessels and the venous network of the right colon. RESULTS: No patients developed complications related to the use of the instrument. CONCLUSION: The instrument of transillumination is a simple and useful tool for facilitating dissection of the right colon segment. In the future, the technique could be used for all types of bowl dissection. PMID- 21029947 TI - Breast carcinoma in Chinese women: does age affect treatment choice and outcome? AB - OBJECTIVE: Age is a known risk factor for breast cancer behaviour. We studied the relationship of age with clinical characteristics, tumour pathology, therapeutic options and outcome in an affluent Asian population. METHODS: From 2003 to 2008, data on newly diagnosed breast carcinoma patients under the care of the multidisciplinary breast cancer team based at a private hospital in Hong Kong were collected prospectively. Patients were divided into three groups: age < 40 years (group I), 41-69 years (group II), and >= 70 years (group III). RESULTS: There were 2,079 patients: 334 in group I, 1,538 in group II and 148 in group III. The clinical presentation and tumour stages were similar. Younger patients had higher tumour grading (p = 0.000) and more lymphovascular permeation (p = 0.011). For older patients, combination therapy was employed less frequently (p < 0.0005), and more radical resection with less reconstructive procedures were performed (p = 0.000). The 3-year disease-free survival was 97.8% and there was no difference between the three groups. CONCLUSION: Although breast cancer in younger Chinese patients was more aggressive pathologically, the differences between clinical presentation, tumour staging and survival were similar. Treatment strategies should follow the clinical condition of the patient rather than age alone. PMID- 21029948 TI - Laparoscopic management of a massive splenic cyst. AB - Splenic cysts are relatively uncommon entities in surgical practice and treatment options vary. We present a case of a young adult woman who presented with a left sided abdominal mass. A large splenic cyst was diagnosed by abdominal ultrasound and computed tomography. Laparoscopic partial excision with marsupialisation was performed with uneventful recovery and minimal blood loss. Histopathology revealed an epidermoid cyst of the spleen. This report describes the case, and includes a short review of the literature. Laparoscopic partial excision with marsupialisation is a safe and appropriate method of treatment for large splenic cysts. PMID- 21029949 TI - Practice guidelines for adult antibiotic prophylaxis during vascular and interventional radiology procedures. Written by the Standards of Practice Committee for the Society of Interventional Radiology and Endorsed by the Cardiovascular Interventional Radiological Society of Europe and Canadian Interventional Radiology Association [corrected]. PMID- 21029950 TI - Percutaneous femoral implantation of an arterial port catheter for intraarterial chemotherapy: feasibility and predictive factors of long-term functionality. AB - PURPOSE: To evaluate the feasibility, functionality, and dysfunctions of an arterial port catheter implanted via the femoral artery. MATERIALS AND METHODS: From November 2001 to May 2008, 93 consecutive patients (mean age 57 years old) with unresectable hepatic colorectal metastases were referred for intraarterial chemotherapy. The arterial port catheters were percutaneously implanted via the femoral artery. The catheter tips were placed as "free-floating" in the common hepatic artery (technique 1), "fixed" in the gastroduodenal artery (technique 2), or inserted in a segmental hepatic artery (technique 3). Embolization of the right gastric artery was always attempted. RESULTS: The technical success rate of the femoral approach was 94% (n = 88 of 93). Intraarterial chemotherapy (average 7.3 courses) was administered to 84 patients. Migration and occlusion of the catheters occurred in 12% (n = 10 of 84) and 11% (n = 9 of 84) of patients, and extrahepatic perfusion occurred in 30% (n = 25 of 84) of patients. Catheter migration occurred significantly more frequently with technique 1 (50%; n = 3 of 6) than with technique 2 (11%; n = 7 of 64; P = .03) or technique 3 (0%; n = 0 of 14; P = .02). Occurrence of gastroduodenal ulcerations was significantly lower (P = .01) when embolization of the right gastric artery was performed (8%; n = 4 of 48) than when it was not (28%; n = 11 of 36). The success rate of embolization of the right gastric artery significantly improved (P = .006) from the first half of patients treated to the second half, resulting in a significant (P = .02) decrease in the occurrence of ulcerations from 28% (n = 12 of 42) in the first half of patients treated to 7% (n = 3 of 42) in the second half. CONCLUSIONS: Percutaneous femoral placement of an arterial port catheter is highly feasible. Right gastric artery embolization and use of techniques 2 and 3 are good predictive factors for long-term functionality. PMID- 21029952 TI - Re: bilateral versus unilateral femoral access for uterine artery embolization results of a randomized comparative trial. PMID- 21029953 TI - Angiojet rheolytic thrombectomy in massive pulmonary embolism: locally efficacious but systemically deleterious? PMID- 21029955 TI - A decade of vaccines: Integrating immunology and vaccinology for rational vaccine design. AB - Vaccination stands as one of the most successful public health measures of the last century. New approaches will be needed, however, to develop highly effective vaccines to prevent tuberculosis, HIV-AIDS, and malaria and to eradicate polio. Current advances in immunology and technology have set the stage for rational vaccine design to begin a "Decade of Vaccines." PMID- 21029956 TI - Vaccines and the future of human immunology. AB - In this issue of Immunity, a collection of detailed reviews summarizes needs, opportunities, and roadblocks to the development of new vaccines, all in the context of our current knowledge and understanding of key aspects of immune function and microbial interactions with the host. This Perspective is designed to provide a broad overview that discusses our present limitations in designing effective novel vaccines for diseases that do not typically induce robust resistance in infected individuals and how the addition of a systems-level, multiplexed approach to the analysis of the human immune system can complement traditional highly focused research efforts to accelerate our progress toward this goal and the improvement of human health. PMID- 21029957 TI - From vaccines to memory and back. AB - Vaccines work by eliciting an immune response and consequent immunological memory that mediates protection from infection or disease. Recently, new methods have been developed to dissect the immune response in experimental animals and humans, which have led to increased understanding of the molecular mechanisms that control differentiation and maintenance of memory T and B cells. In this review we will provide an overview of the cellular organization of immune memory and underline some of the outstanding questions on immunological memory and how they pertain to vaccination strategies. Finally we will discuss how we can learn about antigen design from the interrogation of our memory T and B cells-a journey from vaccines to memory and back. PMID- 21029958 TI - Designing vaccines based on biology of human dendritic cell subsets. AB - The effective vaccines developed against a variety of infectious agents, including polio, measles, and hepatitis B, represent major achievements in medicine. These vaccines, usually composed of microbial antigens, are often associated with an adjuvant that activates dendritic cells (DCs). Many infectious diseases are still in need of an effective vaccine including HIV, malaria, hepatitis C, and tuberculosis. In some cases, the induction of cellular rather than humoral responses may be more important because the goal is to control and eliminate the existing infection rather than to prevent it. Our increased understanding of the mechanisms of antigen presentation, particularly with the description of DC subsets with distinct functions, as well as their plasticity in responding to extrinsic signals, represent opportunities to develop novel vaccines. In addition, we foresee that this increased knowledge will permit us to design vaccines that will reprogram the immune system to intervene therapeutically in cancer, allergy, and autoimmunity. PMID- 21029961 TI - Immunologic basis of vaccine vectors. AB - Efforts to make vaccines against infectious diseases as well as immunotherapies for cancer, autoimmune diseases and allergy have utilized a variety of heterologous expression systems, including viral and bacterial vectors, as well as DNA and RNA constructs. This review explores the immunologic rationale and provides an update of insights obtained from preclinical and clinical studies of such vaccines. PMID- 21029960 TI - Vaccine adjuvants: putting innate immunity to work. AB - Adjuvants enhance immunity to vaccines and experimental antigens by a variety of mechanisms. In the past decade, many receptors and signaling pathways in the innate immune system have been defined and these innate responses strongly influence the adaptive immune response. The focus of this review is to delineate the innate mechanisms by which adjuvants mediate their effects. We highlight how adjuvants can be used to influence the magnitude and alter the quality of the adaptive response in order to provide maximum protection against specific pathogens. Despite the impressive success of currently approved adjuvants for generating immunity to viral and bacterial infections, there remains a need for improved adjuvants that enhance protective antibody responses, especially in populations that respond poorly to current vaccines. However, the larger challenge is to develop vaccines that generate strong T cell immunity with purified or recombinant vaccine antigens. PMID- 21029959 TI - Vaccination strategies to promote mucosal antibody responses. AB - There are great interest and demand for the development of vaccines to prevent and treat diverse microbial infections. Mucosal vaccines elicit immune protection by stimulating the production of antibodies at mucosal surfaces and systemic districts. Being positioned in close proximity to a large community of commensal microbes, the mucosal immune system deploys a heterogeneous population of cells and a complex regulatory network to maintain the balance between surveillance and tolerance. A successful mucosal vaccine relies on leveraging the functions of these immune cells and regulatory components. We review the important cellular interactions and molecular pathways underlying the induction and regulation of mucosal antibody responses and discuss their implications on mucosal vaccination. PMID- 21029962 TI - Systems vaccinology. AB - Vaccination is one of the greatest triumphs of modern medicine, yet we remain largely ignorant of the mechanisms by which successful vaccines stimulate protective immunity. Two recent advances are beginning to illuminate such mechanisms: realization of the pivotal role of the innate immune system in sensing microbes and stimulating adaptive immunity, and advances in systems biology. Recent studies have used systems biology approaches to obtain a global picture of the immune responses to vaccination in humans. This has enabled the identification of early innate signatures that predict the immunogenicity of vaccines, and identification of potentially novel mechanisms of immune regulation. Here, we review these advances and critically examine the potential opportunities and challenges posed by systems biology in vaccine development. PMID- 21029963 TI - Reverse vaccinology: developing vaccines in the era of genomics. AB - The sequence of microbial genomes made all potential antigens of each pathogen available for vaccine development. This increased by orders of magnitude potential vaccine targets in bacteria, parasites, and large viruses and revealed virtually all their CD4(+) and CD8(+) T cell epitopes. The genomic information was first used for the development of a vaccine against serogroup B meningococcus, and it is now being used for several other bacterial vaccines. In this review, we will first summarize the impact that genome sequencing has had on vaccine development, and then we will analyze how the genomic information can help further our understanding of immunity to infection or vaccination and lead to the design of better vaccines by diving into the world of T cell immunity. PMID- 21029965 TI - Malaria vaccine design: immunological considerations. AB - The concept of a malaria vaccine has sparked great interest for decades; however, the challenge is proving to be a difficult one. Immune dysregulation by Plasmodium and the ability of the parasite to mutate critical epitopes in surface antigens have proved to be strong defense weapons. This has led to reconsideration of polyvalent and whole parasite strategies and ways to enhance cellular immunity to malaria that may be more likely to target conserved antigens and an expanded repertoire of antigens. These and other concepts will be discussed in this review. PMID- 21029966 TI - Future vaccination strategies against tuberculosis: thinking outside the box. AB - With almost a dozen vaccine candidates in clinical trials, tuberculosis (TB) research and development is finally reaping the first fruits of its labors. Vaccine candidates in clinical trials may prevent TB disease reactivation by efficiently containing the pathogen Mycobacterium tuberculosis (Mtb). Future research should target vaccines that achieve sterile eradication of Mtb or even prevent stable infection. These are ambitious goals that can be reached only by highly cooperative engagement of basic immunologists, vaccinologists, and clinical researchers--or in other words, by translation from basic immunology to vaccine research and development, as well as reverse translation of insights from clinical trials back to hypothesis-driven research in the basic laboratory. Here, we review current and future strategies toward the rational design of novel vaccines against TB, as well as the progress made thus far, and the hurdles that need to be overcome in the near and distant future. PMID- 21029964 TI - Induction of immunity to human immunodeficiency virus type-1 by vaccination. AB - Recent findings have brought optimism that development of a successful human immunodeficiency virus type-1 (HIV-1) vaccine lies within reach. Studies of early events in HIV-1 infection have revealed when and where HIV-1 is potentially vulnerable to vaccine-targeted immune responses. With technical advances in human antibody production, clues about how antibodies recognize HIV-1 envelope proteins have uncovered new targets for immunogen design. A recent vaccine regimen has shown modest efficacy against HIV-1 acquisition. However, inducing long-term T and B cell memory and coping with HIV-1 diversity remain high priorities. Mediators of innate immunity may play pivotal roles in blocking infection and shaping immunity; vaccine strategies to capture these activities are under investigation. Challenges remain in integrating basic, preclinical and clinical research to improve predictions of types of immunity associated with vaccine efficacy, to apply these insights to immunogen design, and to accelerate evaluation of vaccine efficacy in persons at-risk for infection. PMID- 21029967 TI - Recycling endosomes and TLR signaling--the Rab11 GTPase leads the way. AB - The ability of Toll-like receptors (TLRs) to activate innate immunity depends on their transport to pathogen-containing organelles. In this issue of Immunity, Husebye et al. (2010) report that delivery of TLR4 to phagosomes occurs via a recycling endosome intermediate, which is controlled by the GTPase Rab11a. PMID- 21029968 TI - A Flt3L encounter: mTOR signaling in dendritic cells. AB - The signaling pathway of the cytokine Flt3L in dendritic cells (DCs) is poorly defined. In this issue of Immunity, Sathaliyawala et al. (2010) report that the kinase mTOR functions as a mediator of Flt3L signaling in the development and homeostasis of DCs, particularly of the CD8(+) and CD103(+) DCs. PMID- 21029969 TI - Carcinoembryonic antigen-related cell adhesion molecule-1 regulates granulopoiesis by inhibition of granulocyte colony-stimulating factor receptor. AB - Although carcinoembryonic antigen-related cell adhesion molecule-1 (CEACAM1) is an activation marker for neutrophils and delays neutrophil apoptosis, the role of CEACAM1 in granulopoiesis and neutrophil-dependent host immune responses has not been investigated. CEACAM1 expression correlated with granulocytic differentiation, and Ceacam1(-/-) mice developed neutrophilia because of loss of the Src-homology-phosphatase-1 (SHP-1)-dependent inhibition of granulocyte colony stimulating factor receptor (G-CSFR) signal transducer and activator of transcription (Stat3) pathway provided by CEACAM1. Moreover, Ceacam1(-/-) mice were hypersensitive to Listeria Monocytogenes (LM) infection with an accelerated mortality. Reintroduction of CEACAM1 into Ceacam1(-/-) bone marrow restored normal granulopoiesis and host sensitivity to LM infection, while mutation of its immunoreceptor tyrosine-based inhibitory motifs (ITIMs) abrogated this restoration. shRNA-mediated reduction of Stat3 amounts rescued normal granulopoiesis, attenuating host sensitivity to LM infection in Ceacam1(-/-) mice. Thus, CEACAM1 acted as a coinhibitory receptor for G-CSFR regulating granulopoiesis and host innate immune response to bacterial infections. PMID- 21029970 TI - Asymptomatic primary hyperparathyroidism--commentary on current management. PMID- 21029971 TI - Management of skeletal health in patients with asymptomatic primary hyperparathyroidism. AB - Asymptomatic primary hyperparathyroidism (PHPT) may cause adverse skeletal effects that include high bone remodeling, reduced bone mineral density (BMD), and increased fracture risk. Parathyroid surgery, the definitive treatment for PHPT, has been shown to increase BMD and appears to reduce fracture risk. Current guidelines recommend parathyroid surgery for patients with symptomatic PHPT or asymptomatic PHPT with serum calcium >1mg/dL above the upper limit of normal, calculated creatinine clearance <60 mL/min, osteoporosis, previous fracture, or age <50 yr. The type of operation performed (parathyroid exploration or minimally invasive procedure) and localizing studies to identify the abnormal parathyroid glands preoperatively should be individualized according to the skills of the surgeon and the resources of the institution. In patients who choose not to be treated surgically or who have contraindications for surgery, medical therapy should include a daily calcium intake of at least 1200 mg and maintenance of serum 25-hydroxyvitamin D levels of at least 20 ng/mL (50 nmol/L). Bisphosphonates and estrogens have been shown to provide skeletal benefits that appear to be similar to parathyroid surgery. Cinacalcet reduces serum calcium in PHPT patients with intractable hypercalcemia but has not been shown to improve BMD. It is not known whether any medical intervention reduces fracture risk in patients with PHPT. There are insufficient data on the natural history and treatment of normocalcemic PHPT to make recommendations for management of this disorder. PMID- 21029973 TI - The BMD muddle: the disconnect between bone densitometry results and perception of bone health. AB - We conducted a phenomenological qualitative study to examine fracture patients' interpretations of their most recent bone densitometry results and perceptions of their current bone health. English-speaking outpatients who had sustained a fragility fracture in the previous 18-24 mo and reported having at least 1 previous bone mineral density (BMD) test were eligible. Data were collected through semistructured interviews in patients' homes. Patients were asked to describe their most recent BMD test results and perception of their bone health status based on these results. Eighteen patients (14 women and 4 men) aged 49-82 yr were recruited. BMD results showed bone density in patients to be normal (n=4), osteopenic (n=9), and osteoporotic (n=5). A correct diagnosis was recalled by 6 patients. Two common interpretations of BMD test results emerged: (1) no news was considered to be good news (n=9) and (2) evidence of compromised bone health was not considered to be serious or accurate (n=6). Medication adherence did not appear to be associated with perception of bone health or actual BMD results. Patients' perceptions of their current bone health did not correspond to the results of their most recent BMD test. Standardized bone densitometry reporting may improve patients' understanding of their bone health. PMID- 21029972 TI - Osteoporosis care in the United States after declines in reimbursements for DXA. AB - In January 2007, in the United States (US), Medicare initiated a series of cuts to reimbursement for dual-energy X-ray absorptiometry (DXA) services performed in the nonfacility setting that by January 2010 reduced payments for these services by more than 60% compared with 2006 levels. The objectives of this study were to determine if a temporal association exists between Medicare Physician Fee Schedule changes in office-based DXA reimbursement and attendance at educational conferences for osteoporosis, physicians' perceptions of changes in their medical practices, or national trends in retail prescription medications for osteoporosis in those aged 65 and older. Compared with the 2 yr before the decline in Medicare reimbursement for DXA (2005-2006), attendance at educational meetings for osteoporosis in the US declined in the 2 yr after these cuts (2007-2008) by 6%; declines in attendance were only present in meetings selective for bone densitometry. Survey participants reported changes in DXA services with approximately one-third indicating that they had either decreased the number of DXAs they performed or declined service contracts or hardware/software updates compared with 2005-2006. The number of retail prescriptions for Food and Drug Administration-approved osteoporosis drugs (excluding estrogen compounds and raloxifene) in the age 65 and older population increased by 5.5% in the time period 2007-2008 compared with 2005-2006. However, in the last year of the study (2008), total retail prescriptions for these drugs experienced for the first time over the interval of the study, a decline (1.4%) compared with the previous year. This occurred despite a 2.6% increase in the US population age 65 and older. In conclusion, there were temporal associations noted between Medicare cuts in DXA payments in attendance at educational conferences for bone densitometry, self report of office-based provision of DXA services in the US, and retail prescriptions for osteoporosis therapies. PMID- 21029975 TI - The association of lean mass and fat mass with peak bone mass in young premenopausal women. AB - Total body mass is a major determinant of bone mass, but studies of the relative contributions of lean mass (LM) and fat mass (FM) to bone mass have yielded conflicting results. This is likely because of the use of bone measures that are not adequately adjusted for body size and, therefore, not appropriate for analyses related to body composition, which is also correlated with body size. We examined the relationship between body composition and peak bone mass in premenopausal women aged 18-30 yr using both size-dependent and size-adjusted measures of bone density and body composition, as well as statistical models adjusted for size-related factors. We measured total bone mass and areal bone density using dual-energy X-ray absorptiometry, and used established formulas to calculate estimates of volumetric (size-adjusted) bone density. LM tended to be positively associated with bone both before and after adjustment for size-related factors. FM and body fat percentage, however, were positively associated with size-dependent bone measures, but adjusting for size removed or reversed this association. These findings suggest that the association between bone mass and body composition, especially FM, is dependent on the bone measures analyzed, and that determining the most appropriate size-adjustment techniques is critical for understanding this relationship. PMID- 21029974 TI - Distribution of Z-scores in a University cohort with an emphasis on "high" bone mineral density. AB - High bone mineral density (BMD) is currently not defined by the International Society for Clinical Densitometry with a specific Z-score cutoff; however, it has been suggested that a Z-score greater than or equal to 2.5 is not normal. Institutional Review Board approval was obtained. We evaluated a University dual energy X-ray absorptiometry database over the previous 24 mo to define Z-score distributions. A Z-score greater than or equal to 2.5 was selected as the outcome event of interest in a logistic regression for adjusted odds ratio. The covariates were height; weight; body mass index (BMI); gender; menopausal status; use of female hormones; presence of insufficiency fractures after 50 yr of age; previous fractures; previous surgeries (back surgeries, vertebroplasty, or kyphoplasty); transplant history; presence of long-term chronic conditions (asthma, lupus, rheumatoid arthritis, or cystic fibrosis); eating disorder; current use of glucocorticoids; smoking status; and current and past use of osteoporosis pharmacological therapies. The study included a total of 8216 patients; 7212 (87.8%) were females, and 1044 (12.2%) were males. In the total population, 13.6% had a Z-score greater than or equal to 2.5 at the lumbar spine, femoral neck, or total hip. Only 0.2% of the males and 0.8% of the females had a Z-score greater than or equal to 2.5 at all 3 sites. The 97.5th percentiles for Z scores in our population for men and women, respectively, were 3.4 and 3.9 at the lumbar spine, 1.5 and 2.1 at the femoral neck, and 1.6 and 2.2 at the total hip. The 99th percentile for Z-scores for men and women, respectively, were 4.9 and 4.7 at the lumbar spine, 2.4 and 2.7 at the femoral neck, and 2.2 and 2.7 at the total hip. At the lumbar spine, female gender and weight were found to be risk factors for a high Z-score (>= 2.5). The use of glucocorticoids, bone-active medications, BMI, and smoking were significantly less likely to predict a lumbar spine Z-score greater than or equal to 2.5. A high total-hip Z-score is predicted by increasing weight, whereas those patients using bone-active medications were less likely to have high BMD at the total hip. At the femoral neck, there were no significant risk factors related to a Z-score greater than or equal to 2.5; those taking bone-active medications were significantly less likely to have a high Z score. These data suggest that a high Z-score is common at 1 or more sites. Further research about the criteria for the diagnosis of high BMD is warranted. PMID- 21029976 TI - The ability of hand digital X-ray radiogrammetry to identify middle-aged and elderly women with reduced bone density, as assessed by femoral neck dual-energy X-ray absorptiometry. AB - In this study, we evaluate the ability of digitized digital X-ray radiogrammetry (DXR) bone mineral density (BMD) to identify women with reduced BMD at femoral neck, assessed by dual-energy X-ray absorptiometry (DXA). The study population contained women with recent low-energy distal radius fracture and women recruited from the general population, all aged 50 yr or older. The correlation between hand BMD and femoral neck BMD was r=0.65 (p<0.001). We used a triage approach where 2 cutoffs for DXR T-score were defined at which patients with 90% sensitivity and 90% specificity could be identified to have or not have reduced BMD at femoral neck, defined as T-score <=-2.5 standard deviation (SD). The upper and lower DXR T-score cutoffs were -1.2 and -2.7, respectively. Applying the triage approach in the whole cohort, 32% would require a central DXA assessment to determine the presence or absence of femoral neck T-score <=-2.5 SD. Our data suggest that DXR can be used to reduce the numbers of patients in need of DXA femoral neck and may, thus, be of clinical value where access to DXA is limited. PMID- 21029977 TI - Quantification of bone density of the proximal femur after hip resurfacing arthroplasty--comparison of different DXA acquisition modes. AB - Total hip arthroplasty (THA) is a traditional operative procedure in the treatment of osteoarthritis. The hip resurfacing arthroplasty (HRA) provides an alternative to the THA for young active patients. HRA is a bone-preserving procedure eliminating the problem of proximal femoral stress shielding and osteolysis associated to THA. Unfortunately, there is no standardized methodology to monitor the quality of bone after HRA. In this study, areal bone mineral density (BMD) in the operated hip (10 regions of interests [ROIs] of 34 volunteered HRA patients) was measured using Lunar Prodigy dual-energy X-ray absorptiometry, and the agreement of a standard (dual femur) and an orthopedic (orthopedic hip) acquisition modes was compared. Furthermore, reproducibility of the patient-specific analysis procedures was tested. The analysis procedures were reproducible with both acquisition modes (1.18%-1.37%). The mean (+/- standard deviation) difference between the acquisition modes was 1.46 +/- 0.93%. At ROIs, a strong linear relationship was found between the results from 2 acquisition modes (R(2)=0.801-0.966, p<0.01). In conclusion, both acquisition modes were reproducible, and it is suggested that the error induced by the different acquisition modes does not affect interpretation of BMD changes after HRA surgery. PMID- 21029978 TI - Low bone mineral density in rotating-shift workers. AB - Shift workers have been reported to have an increased bone resorption. However, no existing evidence indicates lower bone mineral density (BMD) in this group. The objective of this study was to test the hypothesis that a rotating-shift work schedule is associated with low BMD and osteoporosis. We evaluated 70 postmenopausal nurses from the Naval Hospital in Concepcion, Chile. The participants were categorized according to the type of work schedule: 39 had a rotating shift and 31 were daytime workers. Medical history, a health examination, a questionnaire on health-related behaviors and biochemical determinations, and BMD examination were obtained for all participants. When comparing the 2 groups, the rotating-shift workers had lower BMD in the lumbar spine (L1-L4: 0.957 +/- 0.15 vs 1.104 +/- 0.13; p<0.05) and lower bone density in both femoral neck bones (right: 0.936 +/- 0.17 vs 1.06 +/- 0.12; p<0.05 and left: 0.956 +/- 0.19 vs 1.05 +/- 0.12; p<0.05). Additionally, the T-scores for 10 (25.6%) of the rotating-shift workers indicated osteoporosis at lumbar spine (T score>-2.5). No evidence of osteoporosis was found for daytime workers. When comparing the 2 groups, the rotating-shift workers had a higher prevalence of osteopenia (T-score=-1.0 to -2.5) than the daytime workers: 46.2% vs 35.5%, respectively. We found significant evidence that rotating-shift workers have lower BMD in the trabecular and cortical bones, thus suggesting that this type of work may be a risk factor for osteoporosis. Because this is the first time that this osteoporosis risk factor has been reported, the association needs to be replicated and confirmed in other settings. PMID- 21029980 TI - Slow progress towards universal access. PMID- 21029981 TI - Loss of antibodies, but not of protection. PMID- 21029982 TI - Treating malaria in pregnant women: a pressing problem. PMID- 21029983 TI - Dangerous horseplay. PMID- 21029984 TI - New Delhi metallo-beta-lactamase 1. PMID- 21029985 TI - New Delhi metallo-beta-lactamase 1. PMID- 21029986 TI - New Delhi metallo-beta-lactamase 1. PMID- 21029987 TI - New Delhi metallo-beta-lactamase 1. PMID- 21029988 TI - New Delhi metallo-beta-lactamase 1. PMID- 21029989 TI - New Delhi metallo-beta-lactamase 1. PMID- 21029991 TI - New Delhi metallo-beta-lactamase 1. PMID- 21029992 TI - Generic antibiotics, antibiotic resistance, and drug licensing. PMID- 21029994 TI - Transitions. PMID- 21029993 TI - Cryptococcal immune reconstitution inflammatory syndrome in HIV-1-infected individuals: proposed clinical case definitions. AB - Cryptococcal immune reconstitution inflammatory syndrome (IRIS) may present as a clinical worsening or new presentation of cryptococcal disease after initiation of antiretroviral therapy (ART), and is thought to be caused by recovery of cryptococcus-specific immune responses. We have reviewed reports of cryptococcal IRIS and have developed a consensus case definition specifically for paradoxical crytopcoccal IRIS in patients with HIV-1 and known cryptococcal disease before ART, and a separate definition for incident cryptococcosis developed during ART (termed ART-associated cryptococcosis), for which a proportion of cases are likely to be unmasking cryptococcal IRIS. These structured case definitions are intended to aid design of future clinical, epidemiological, and immunopathological studies of cryptococcal IRIS, to standardise diagnostic criteria, and to facilitate comparisons between studies. As for definitions of tuberculosis-associated IRIS, definitions for cryptococcal IRIS should be regarded as preliminary until further insights into the immunopathology of IRIS permit their refinement. PMID- 21029995 TI - Pain tolerance and obstructive sleep apnea in the elderly. AB - OBJECTIVE: Patients with painful conditions often suffer from sleep disturbances. However, changes in sleep pattern per se could also influence pain tolerance. Untreated obstructive sleep apnea (OSA) causes major disturbances in sleep pattern. The aim of this study was to assess whether continuous positive airway pressure (CPAP) treatment in elderly patients with OSA would result in improved pain tolerance. DESIGN: Randomized, double-blind crossover study. SETTING: Geriatric sleep center based in Antoine Charial University Hospital (Lyon, France). PARTICIPANTS: A total of 13 consecutive OSA patients aged 70 and older randomly assigned CPAP treatment (lowCPAP versus highCPAP). Eleven patients completed the study. MEASUREMENTS: Overnight sleep recording, electrical pain tolerance assessment, and visual analog scale for sleep quality were performed. RESULTS: Both low- and highCPAP treatment significantly improved respiratory parameters. However, compared with baseline, the electrical pain tolerance score was significantly enhanced (analgesic effect) only under highCPAP treatment (21.2 +/- 10.9 versus 28.4 +/- 16.0; P = .03). CONCLUSION: The treatment of OSA with CPAP would have an analgesic effect. This would represent a unique outcome attributed to CPAP treatment. Given the high prevalence of both OSA and chronic pain conditions in the elderly; our findings could hold many implications for very large segments of the elderly population. PMID- 21029996 TI - Possible role of serum 25-hydroxyvitamin D in black-white health disparities in the United States. AB - Significant health disparities exist between African Americans (AAs) and White Americans (WAs). The all-cause mortality rate for AAs in 2006 was 26% higher than for non-Hispanic WAs. Explanations for the disparities usually include socioeconomic status, lifestyle behaviors, social environment, and access to preventive health care services. However, several studies indicate that these factors do not account for the observed disparities. Many studies report that vitamin D has important health benefits through paracrine and autocrine mechanisms and that higher serum 25-hydroxyvitamin D (25[OH]D) levels are associated with better health outcomes. AAs have a population mean serum 25(OH)D level of 16 ng/mL, whereas WAs have a level of 26 ng/mL. From preliminary meta analyses of serum 25(OH)D level-disease outcome from observational studies, differences in serum 25(OH)D level for AAs and WAs can explain many of the health disparities. The ratios of mortality rates for AAs to WAs for female breast cancer, colorectal cancer, cardiovascular disease, and all-cause mortality rate in 2006 were 1.34, 1.43, 1.29, and 1.26, respectively. The 25(OH)D level-disease outcome ratios for 16 ng/mL versus 26 ng/mL for the same diseases were 1.26, 1.44, 1.27, and 1.26, respectively. The close agreement between these 2 sets of numbers suggests that low serum 25(OH)D level is an important health risk for AAs. Given the widespread vitamin D deficiency in the AA population and the potential widespread health benefits that accompany adequate replacement, we believe that addressing this issue may be the single most important public health measure that can be undertaken. PMID- 21029997 TI - Transitions in long-term care and potential implications for quality reporting in Ontario, Canada. AB - PURPOSE: To describe the proportion of long-term care (LTC) residents excluded from quality measurement because of standard length of stay inclusion criteria and the extent to which this varies across facilities. DESIGN AND METHODS: A 2005 province-wide census of LTC residents' charts was linked to additional databases from Ontario, Canada. The proportion of residents who were newly admitted (<=90 days) and who exited the facility within 90 days were identified and interfacility variation in each was described. RESULTS: Of the 68,930 residents in 574 facilities, 5363 (7.8%) were admitted in the prior 90 days and 7833 (11.4%) were discharged in the subsequent 90 days. Overall, 55,734 (80.4%) residents were neither admitted nor discharged within 90 days and were defined as "stable"; however, this ranged from 67.2% to 95.1% across facilities. IMPLICATIONS: Stable residents are the focus of most quality measurement in LTC but transitioning residents are an important part of the caseload for these facilities. In Ontario, transitioning residents accounted for 20% of the population but there was substantial variation in this proportion across facilities. This raises concerns about the comprehensiveness and comparability of publicly reported quality indicators for a population with frequent transitions in Ontario and elsewhere. PMID- 21029998 TI - Memantine discontinuation and the health status of nursing home residents with Alzheimer's disease. AB - OBJECTIVE: To estimate the effect of memantine discontinuation for a nonmedical reason (eg, formulary restriction or family decision) on the health status of nursing home (NH) residents with Alzheimer's disease (AD). DESIGN: Retrospective chart review. SETTING: NHs (n = 113) in the United States. PARTICIPANTS: Residents (minimum stay of 90 days) with AD, continuously treated with memantine (MC: n = 273) or discontinued for 60 days or longer (MD: n = 248). The subset of patients who discontinued for a nonmedical reason (MD-N: n = 163) was also analyzed, as was the subset of patients in groups MC and MD-N whose doses of concomitant medications remained stable (MC(s): n = 185; MD-N(s): n = 70). MEASUREMENTS: Thirty-one common geriatric and AD symptoms from NH charts were scored based on their emergence or resolution (+1 or -1 points, respectively), worsening or improvement (+0.5 or -0.5 points, respectively), or absence of change (0 points), compared with the baseline period (the first 30 days analyzed in the charts, during which all residents received memantine treatment). Patients' weight change was also captured. RESULTS: Compared with continuous treatment, memantine discontinuation was associated with a significant increase in the Total AD Symptom Change Score (ie, worsening) in all comparison pairs (MC versus MD, MC versus MD-N, and MC(s) versus MD-N(s): P < .001 for all). The symptoms showing greatest worsening aggregated into two factors: cognition and mood. CONCLUSION: Memantine discontinuation in NH residents with AD may be associated with declining health status, and should be considered with care. A randomized, placebo-controlled trial of treatment discontinuation is merited. PMID- 21029999 TI - Does self-reported function correspond to objective measures of functional impairment? AB - INTRODUCTION: The relationship between self-reported function and objective measures of physiological function among disabled older women was analyzed to determine the validity of self-reported function, and to identify the hierarchy of self-reported task difficulty most associated with loss of independence as a basis to inform treatment progress goals. METHODS: A randomly selected population of older women with moderate to high disability was selected from community dwelling women 65 to 101 years old from the Women's Health and Aging Study I baseline evaluation (n = 987). Cross-sectional analyses evaluated the association of self-reported function with objective physiological impairment measures. RESULTS: The results indicated that (1) disabled older women self-reported a broad range of physical function levels; (2) self-reported function correlated closely with objective measures of physiological impairments; (3) "preclinical disability," as measured by self-reported modification of task performance in the absence of perceived difficulty, has validity even in a disabled population, and identifies a group intermediate between those who are high functioning in a task and those with difficulty; and (4) there is an apparent gradation in physiological impairment measures with reported loss of functional independence. CONCLUSION: These findings suggest the validity of self-report functional disability measures and the potential to use these measures to identify already disabled older adults at risk for further functional degradation and potential targets for intervention. PMID- 21030000 TI - Are standing order programs associated with influenza vaccination? - NNHS, 2004. AB - BACKGROUND: Influenza vaccination coverage among nursing home residents has consistently been reported well below the Healthy People goals. We sought to determine if standing order programs (SOPs) in long-term care facilities are associated with greater influenza vaccination coverage among residents. METHODS: The National Nursing Home Survey (2004) is cross-sectional. A total of 1152 US long-term care facilities were systematically sampled with probability proportional to number of beds. A total of 11,939 people aged 65 years or older residing in sampled long-term care facilities between August and December 2004 were randomly sampled. Influenza vaccination coverage of residents was obtained from facility records. Facility's immunization program included standing orders versus other (preprinted admission order, advance physician order, personal physician order, and no program). Multinomial logistic regression was used to examine the relationship between type of influenza immunization program and receipt of vaccination, adjusted for resident and facility confounders. RESULTS: The proportion of residents aged 65 years or older who received influenza vaccination was 64%; 41% of residents lived in a facility with an SOP. Influenza vaccination coverage among residents residing in facilities with standing orders was 68% compared with 59% to 63% of residents in facilities with other program types. Logistic regression showed that standing order programs were independently associated with greater influenza vaccination coverage (66.7% versus 62.0%, P < .01). CONCLUSION: This study indicates that residents in long-term care facilities having standing order programs for influenza were more likely to be immunized. More research needs to be done to understand how to facilitate adoption of these programs. PMID- 21030001 TI - Dementia care redesigned: Effects of small-scale living facilities on residents, their family caregivers, and staff. AB - OBJECTIVE: The purpose of this study was to evaluate the effects of small-scale living facilities in dementia care on residents, family caregivers, and staff. DESIGN: This was a quasi-experimental study including 2 types of institutional nursing care: small-scale living facilities (experimental group), and regular psychogeriatric nursing home wards (control group). Three measures were conducted: at baseline and follow-ups after 6 and 12 months. SETTING: Twenty eight houses in small-scale living facilities and 21 regular psychogeriatric nursing home wards. PARTICIPANTS: In total, 259 residents were included in the study: 124 in small-scale living facilities and 135 controls, matched on cognitive and functional status. Furthermore, 229 family caregivers were included and 305 staff members. MEASUREMENTS: For residents, main outcome measures were quality of life, neuropsychiatric symptoms, and agitation. Main outcome measures for family caregivers included perceived burden, satisfaction, and involvement with care. Main outcome measures for staff were job satisfaction and motivation. RESULTS: No effects were found for residents' total quality of life, neuropsychiatric symptoms, and agitation. Family caregivers in small-scale living reported significantly less burden (adjusted mean difference 0.8, 95% CI 0.1-1.5) and were more satisfied with nursing staff (0.3, 0.2-0.5) than family caregivers in regular wards. No differences were found in their involvement with care. Overall, no significant differences were found for staff's job satisfaction and motivation, although subgroup analyses using contrast groups (regarding typical small-scale living and regular wards) revealed more job satisfaction (2.0, 0.5 3.5) and motivation (0.6, 0.0-1.3) in small-scale living compared with regular wards. CONCLUSION: This study was unable to demonstrate convincing overall effects of small-scale living facilities. Because governmental policies and, in some countries, financial support, are increasingly aimed at providing small scale, homelike care, it is suggested that this may not be a final solution to accomplish high-quality dementia care and that other options should be considered. PMID- 21030002 TI - Clinical status: a daily forum for resident discussion and staff education. AB - A forum at which the timely transmission of critical clinical information is coupled with a formal interdisciplinary teaching program has tremendous value in the long-term care setting. We have combined features of morning report used in teaching hospitals with attributes of "stand-up" meetings to fill this need. Each morning we hold Clinical Status, a gathering of representative staff from all neighborhoods (units) at which we discuss problems that have occurred during the previous 24 hours; admissions, discharges, and transitions; Center-wide concerns such as infection control measures; and upcoming events such as celebrations, lectures, and memorials. In addition, short educational presentations are made by staff members at each session. A survey of attendees confirms our impression that Clinical Status is regarded as an informative, stimulating and vital aspect of life at the Center. PMID- 21030003 TI - Hurricane Katrina: more lessons learned. AB - In August of 2007, the author testified as the medical expert witness on behalf of the State of Louisiana in the St. Rita's Nursing Home criminal case. Thirty five residents drowned as floodwaters swept over the nursing home during Hurricane Katrina. For nursing home owners, administrators, and medical staff leadership, there are additional lessons to be learned from this catastrophe. PMID- 21030004 TI - Missed opportunities: Nursing home providers' ability to identify and recognize depressive symptoms. PMID- 21030005 TI - Differential dynamics of spatial and non-spatial stimulus-response compatibility effects: a dual task LRP study. AB - Choice reaction times are shorter when stimulus and response features are compatible rather than incompatible. Recent studies revealed that spatial compatibility effects in Simon tasks are strongly attenuated when there is temporal overlap with a different high-priority task. In contrast, non-spatial variants of the Simon task appear to be unaffected by task overlap. The present study used the lateralized readiness potential (LRP) within a dual task design to elucidate the dynamics underlying these differential effects for a color and a spatial variant of the Simon task. In the color version there was no sign of early response priming by irrelevant stimulus features in the LRP. The color compatibility effect was independent of task overlap and reflected in the LRP onset latency. In contrast, in the spatial version, priming by irrelevant stimulus location showed up and was mirrored by early LRP activation. Response priming and the corresponding Simon effect, however, were present only in case of little temporal overlap with the primary task. The absence of spatial compatibility effects at strong temporal overlap suggests that response conflicts due to stimulus-related priming depend on the availability of processing resources. PMID- 21030006 TI - Treatment of type 2 diabetes: New clinical studies and effects of GLP-1 on macrovascular complications. AB - Various publications in 2009 showed that the treatment of type 2 diabetic (T2D) patients with macrovascular complications is still a controversial subject, whether with regard to the use of glitazones, to the best management strategy for T2D patients with stable coronary artery disease or to the use of incretin mimetic drugs in patients with heart disease. The Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of glycemia in Diabetes study (RECORD) compared cardiovascular morbidity-mortality outcomes in patients taking rosiglitazone in combination with metformin or sulfonylurea versus metformin with sulfonylurea. The results showed that rosiglitazone was not inferior to the metformin sulfonylurea combination in terms of mortality and cardiovascular hospitalization, but caution must be used when interpreting the results, as the event rate was low. The BARI 2D study (Bypass Angioplasty Revascularization Investigation 2 Diabetes) is a cardiovascular morbidity-mortality trial with the goal of determining the best strategy for blood glucose control and revascularization in T2D patients with stable coronary artery disease. The results of this trial showed that early revascularization is not clearly beneficial, except in a subgroup of patients in whom surgical revascularization is indicated. The use of GLP-1 analogs (Glucagon-Like Peptide-1) in the acute phase of myocardial ischemia in animal models provided promising results. Some clinical studies also suggest an improvement in cardiovascular risk factors with these treatments. Results from morbidity-mortality studies are needed to better assess the long-term efficiency of these new drugs. PMID- 21030007 TI - Sequential induction of marrow stromal cells by FGF2 and BMP2 improves their growth and differentiation potential in vivo. AB - BACKGROUND: repairing bone loss by autologous grafting requires that a patient's marrow stromal cells (MSCs) be collected and cultured until the number of cells is adequate for implantation. Currently used techniques allow a slow proliferation rate and produce a culture that contains only small amounts of pluripotent stem cells that will become osteoblasts in culture. OBJECTIVE: to develop culture conditions that permit a rapid increase in the number of MSCs while retaining or improving their potential for complete differentiation in vivo. RESULTS: sequential applications of low doses of basic fibroblast growth factor 2 (FGF2) and bone morphogenetic protein 2 (BMP2) improved the growth and differentiation potential of MSCs. FGF2 also elevated sensitivity of the cells to BMP2. BMP2 increased the syntheses of alkaline phosphatase (ALP), collagen type I and bone sialoprotein, while FGF2 increased the expression of osteocalcin (OC). Full induction as determined by the formation of mineralised nodules in vitro was observed within 7 days. Seeding the induced cells onto scaffolds and then implanting them into nude mice resulted in newly formed bone 4 weeks later. The results of real-time polymerase chain reaction (PCR) and Western blotting suggested that FGF2 increased the pool of committed osteoblasts by up-regulating the Cbfa1/Runx2 gene. The later stages of bone formation seemed to be induced by Cbfa1/Runx2-downstream factors such as BMP2, ALP, collagen type I, bone sialoprotein and OC. CONCLUSION: the culture system that was developed increased both the proliferation of MSC and the proportion that developed into pre osteoblasts. PMID- 21030008 TI - Structural magnetic resonance imaging in bipolar disorder: an international collaborative mega-analysis of individual adult patient data. AB - BACKGROUND: There is substantial inconsistency in results of brain structural magnetic resonance imaging studies in adult bipolar disorder. This is likely consequent upon limited statistical power of studies together with their clinical and methodological heterogeneity. The current study was undertaken to perform an international collaborative mega-analysis of regional volumetric measurements of individual patient and healthy subject data, to optimize statistical power, detect case-control differences, assess the association of psychotropic medication usage with brain structural variation, and detect other possible sources of heterogeneity. METHODS: Eleven international research groups contributed published and unpublished data on 321 individuals with bipolar disorder I and 442 healthy subjects. We used linear mixed effects regression models to evaluate differences in brain structure between patient groups. RESULTS: Individuals with bipolar disorder had increased right lateral ventricular, left temporal lobe, and right putamen volumes. Bipolar patients taking lithium displayed significantly increased hippocampal and amygdala volume compared with patients not treated with lithium and healthy comparison subjects. Cerebral volume reduction was significantly associated with illness duration in bipolar individuals. CONCLUSIONS: The application of mega-analysis to bipolar disorder imaging identified lithium use and illness duration as substantial and consistent sources of heterogeneity, with lithium use associated with regionally specific increased brain volume. PMID- 21030009 TI - Exposure to cocaine alters dynorphin-mediated regulation of excitatory synaptic transmission in nucleus accumbens neurons. AB - BACKGROUND: Dysregulation of excitatory synaptic input to nucleus accumbens (NAc) medium spiny neurons (MSNs) underlies a key pathophysiology of drug addiction and addiction-associated emotional and motivational alterations. Dynorphin peptides, which exhibit higher affinity to kappa type opioid receptors, are upregulated within the NAc upon exposure to cocaine administration, and the increased dynorphin-signaling in the NAc has been critically implicated in negative mood observed in cocaine- or stress-exposed animals. Despite such apparent behavioral significance of the NAc dynorphins, the understanding of how dynorphins regulate excitatory synaptic transmission in the NAc remains incomplete. METHODS: We used electrophysiological recording in brain slices to examine the effects of dynorphins on excitatory synaptic transmission in the NAc. RESULTS: We focused on two key dynorphins, dynorphin A and B. Our current results show that dynorphin A and B differentially regulated excitatory postsynaptic currents (EPSCs) in NAc MSNs. Whereas perfusions of both dynorphin A and B to NAc slices decreased EPSCs in MSNs, the effect of dynorphin A but not dynorphin B was completely reversed by the kappa receptor-selective antagonist nor-binaltorphimine. These results implicate kappa receptor-independent mechanisms in dynorphin B-mediated synaptic effects in the NAc. Furthermore, repeated exposure to cocaine (15 mg/kg/day via intraperitoneal injection for 5 days, with 1, 2, or 14 days withdrawal) completely abolished dynorphin A-mediated modulation of EPSCs in NAc MSNs, whereas the effect of dynorphin B remained largely unchanged. CONCLUSIONS: Given the quantitatively higher abundance of dynorphin B in the NAc, our present results suggest that the dynorphin B-mediated, kappa receptor-independent pathways predominate in the overall effect of dynorphins in cocaine-pretreated animals and potentially in cocaine-induced alterations in mood. PMID- 21030010 TI - Dimensions of depression and anxiety and the hypothalamo-pituitary-adrenal axis. AB - BACKGROUND: Results on the association between depression and the hypothalamo pituitary-adrenal (HPA) axis have been inconsistent, possibly due to heterogeneity of the DSM-IV category of depression. Specific symptom-dimensions could be used as a more homogenous phenotype in HPA-axis research. METHODS: Subjects (n = 1029) with a lifetime depression and/or anxiety disorder from the NESDA study (Netherlands Study of Depression and Anxiety) (mean age: 43.0 +/- 12.7 years, 67.4% women) provided seven saliva samples to yield the cortisol awakening response (CAR), evening cortisol, and dexamethasone suppression data. The dimensions of the tripartite model (General Distress, Anhedonic Depression, and Anxious Arousal) were measured with the 30-item adapted Mood and Anxiety Symptoms Questionnaire (MASQ-D30) and analyzed in association with the cortisol measures with linear and nonlinear regression. RESULTS: Median (interquartile range) scores of General Distress, Anhedonic Depression, and Anxious Arousal were 20 (14-27), 36 (28-44), and 15 (12-19), respectively, indicating large variability. Nonlinear associations with the shape of an inverted U were found between General Distress, Anhedonic Depression, and Anxious Arousal on one hand and total morning secretion and the dynamic of the CAR by contrast. Both high and low severity levels were associated with a lower CAR, compared with intermediate levels of severity. Most of the associations remained significant when adjusted for covariates and the presence of DSM-IV diagnoses. CONCLUSIONS: Nonlinear associations were found between the CAR and the dimensions of the tripartite model. This could explain previous inconsistent findings regarding HPA-axis activity in depressed patients and illustrates the added value of symptom dimensions for HPA-axis research. PMID- 21030012 TI - [Surgical treatment of pancreatic adenocarcinoma using cephalic duodenopancreatectomy (Part 2). Long term follow up after 204 cases]. AB - INTRODUCTION: Surgery is the accepted treatment in adenocarcinoma of the head of the pancreas; however, the long-term survival continues to be low. The aim of this study is to define prognostic factors of long-term survival after cephalic duodenopancreatectomy due to pancreatic adenocarcinoma. MATERIAL AND METHODS: We have collected data on the treatment of adenocarcinoma of the head of the pancreas (ADHP) by means of a cephalic duodenopancreatectomy (CDP) performed n the Bellvitge University Hospital (Barcelona) from 1991 to 2007. RESULTS: A total of 204 CDP due to ADHP were performed. The histology showed that the resected tumour was larger than 3cms in 70 cases, with lymphatic infiltration in 73%, perineural invasion in 89%, and lymphatic involvement in 89%. More than 15 lymph nodes were resected in 120 patients. A total of 113 (60%) patients received adjuvant treatment after surgery. There were 148 (73%) deaths, of which 55 (27%) were alive at closure. The actual mean survival was 2.54 years (95% CI; 2.02 3.07) and an actuarial survival at 5 years of 13.55% (95% CI; 7.69-19.41). The study of mortality risk factors showed that, female gender, absence of peri operative transfusion (p=0.003), the resection of more than 15 lymph nodes during the operation (P=0.004), and the administration of adjuvant treatment (p=0.004) had a better long-term prognosis. The multivariate analysis showed that transfusion and gender were the most significant variables. CONCLUSIONS: Surgery of head of the pancreas adenocarcinoma must include an adequate lymphadectomy, and must be performed with a low morbidity and without the need of a peri operative transfusion. PMID- 21030013 TI - Do English and Mandarin speakers think about time differently? AB - Time is a fundamental domain of experience. In this paper we ask whether aspects of language and culture affect how people think about this domain. Specifically, we consider whether English and Mandarin speakers think about time differently. We review all of the available evidence both for and against this hypothesis, and report new data that further support and refine it. The results demonstrate that English and Mandarin speakers do think about time differently. As predicted by patterns in language, Mandarin speakers are more likely than English speakers to think about time vertically (with earlier time-points above and later time-points below). PMID- 21030011 TI - Secretion of MIP-1beta and MIP-1alpha by CD8(+) T-lymphocytes correlates with HIV 1 inhibition independent of coreceptor usage. AB - CD8(+) T-lymphocytes can utilize noncytolytic mechanisms to suppress HIV-1 replication through the secretion of soluble factors. The secretion of MIP-1beta, MIP-1alpha, IP-10, MIG, IL-1alpha, and interferon gamma correlated most strongly with soluble noncytolytic suppression (p<0.0001). Since the noncytolytic response is impaired by histone hyperacetylation, we examined the ability of histone hyperacetylation to alter the expression of immune-related genes. MIP-1alpha and IP-10 were also among the genes that were down-regulated by histone hyperacetylation. We define a multifactorial cytokine profile of CD8(+) T lymphocytes capable of mediating noncytolytic suppression of CXCR4-tropic HIV-1 replication. PMID- 21030014 TI - The relationship between isolated teratozoospermia and clinical pregnancy after in vitro fertilization with or without intracytoplasmic sperm injection: a systematic review and meta-analysis. AB - We conducted a systematic review and meta-analysis of data from the literature from the years 1986 to 2009 using teratozoospermia and fertilization or IVF or in vitro fertilization as the keywords. A total of 31 studies were identified, and 4 met the inclusion criteria. Isolated teratozoospermia was not associated with a statistically significantly decreased probability of pregnancy with assisted reproduction. PMID- 21030015 TI - Prevalence of chronic endometritis in recurrent miscarriages. AB - Chronic endometritis was identified immunohistochemically in 9.3% of patients with recurrent miscarriages (in 12.9% of patients with miscarriages of unknown etiology). Chronic endometritis is not negligible in patients with recurrent miscarriages. PMID- 21030016 TI - Comet assay on mouse oocytes: an improved technique to evaluate genotoxic risk on female germ cells. AB - OBJECTIVE: To develop and validate an efficient comet assay on mouse oocytes without depellucidation. DESIGN: In vitro experiments using a murine model. SETTING: Biogenotoxicology research laboratory in Aix-Marseille II University, France. ANIMAL(S): CD1 prepubescent female mice. INTERVENTION(S): DNA lesions in oocytes were evaluated by the alkaline comet assay. After oocyte retrieval, we first studied the effect of zona pellucida (ZP) on comet morphology. For this study, we applied the comet assay to mature oocytes with and without ZP after exposure to simulated sunlight irradiation (SSI) compared with negative controls. Next, nondepellucidated mouse oocytes were exposed to three well-known genotoxic agents (SSI, methylmethanesulfonate [MMS], and hydrogen peroxide [H(2)O(2)]) and compared with negative controls. Images of oocytes were analyzed with Komet software. MAIN OUTCOME MEASURE(S): DNA damages were quantified and expressed as olive tail moment (OTM), defined as the product of the tail length and the fraction of total DNA in the tail. OTMchi(2) were calculated from OTM; they corresponded to the degrees of freedom (n) of each OTM distribution obtained from at least 50 oocytes. OTMchi(2) is an indicator of DNA lesions. The test was considered positive and statistically significant when OTMchi(2) increased in oocytes compared with the medium-only control cells. RESULT(S): There was no difference in comet aspect between oocyte groups with and without ZP. The three genotoxic agents significantly increased DNA damages as compared with the control groups. The OTMchi(2) values were (mean +/- SD): 2.1 +/- 0.07, 7.73 +/- 0.35, 3.35 +/- 0.15, and 12.4 +/- 0.51 in control, SSI, MMS, and H(2)O(2) groups, respectively. CONCLUSION(S): Comet assay on non depellucidated mouse oocytes is a rapid and easy test. This assay would be useful to assess the genotoxicity on female germ cells of chemicals, drugs, or environmental pollutants and the efficiency of antioxidant molecules. PMID- 21030017 TI - A prospective, multicenter study of 1111 colorectal endoscopic submucosal dissections (with video). AB - BACKGROUND: Endoscopic submucosal dissection (ESD) is accepted as a minimally invasive treatment for early gastric cancer, although it is not widely used in the colorectum because of technical difficulty. OBJECTIVE: To examine the current status of colorectal ESDs at specialized endoscopic treatment centers. DESIGN AND SETTING: Multicenter cohort study using a prospectively completed database at 10 specialized institutions. PATIENTS AND INTERVENTIONS: From June 1998 to February 2008, 1111 colorectal tumors in 1090 patients were treated by ESD. MAIN OUTCOME MEASUREMENTS: Tumor size, macroscopic type, histology, procedure time, en bloc and curative resection rates and complications. RESULTS: Included in the 1111 tumors were 356 tubular adenomas, 519 intramucosal cancers, 112 superficial submucosal (SM) cancers, 101 SM deep cancers, 18 carcinoid tumors, 1 mucosa associated lymphoid tissue lymphoma, and 4 serrated lesions. Macroscopic types included 956 laterally spreading tumors, 30 depressed, 62 protruded, 44 recurrent, and 19 SM tumors. The en bloc and curative resection rates were 88% and 89%, respectively. The mean procedure time +/- standard deviation was 116 +/- 88 minutes with a mean tumor size of 35 +/- 18 mm. Perforations occurred in 54 cases (4.9%) with 4 cases of delayed perforation (0.4%) and 17 cases of postoperative bleeding (1.5%). Two immediate perforations with ineffective endoscopic clipping and 3 delayed perforations required emergency surgery. Tumor size of 50 mm or larger was an independent risk factor for complications, whereas a large number of ESDs performed at an institution decreased the risk of complications. LIMITATIONS: No long-term outcome data. CONCLUSIONS: ESD performed by experienced endoscopists is an effective alternative treatment to surgery, providing high en bloc and curative resection rates for large superficial colorectal tumors. PMID- 21030018 TI - Endoscopic submucosal dissection with the pulley method for early-stage gastric cancer (with video). AB - BACKGROUND: Using EMR techniques, physicians frequently remove tumors >15 mm by piecemeal resection, which is associated with an increased rate of disease recurrence and difficulty in histologically evaluating the specimen. Endoscopic submucosal dissection (ESD) of early-stage gastric cancer improves the rate of successful en bloc resection, but it is associated with more complications, such as bleeding and perforation, than conventional EMR. OBJECTIVE: To describe a simple technique that uses the pulley method to facilitate ESD procedures in the excision of large early-stage gastric cancers. DESIGN: Case series. SETTING: Tertiary medical center in Taiwan. PATIENTS AND METHODS: Eleven patients with early-stage gastric cancers or adenomas >20 mm underwent ESD. INTERVENTIONS: The pulley method with standard clips and dental floss was used to provide traction to improve visualization of the dissection plane during ESD. MAIN OUTCOME MEASUREMENT: Proportion with complete en bloc resection. RESULTS: En bloc resection of the lesion was achieved in 11 patients. No perforation or emergent surgery was noted. LIMITATIONS: One endoscopist performed all procedures, and only 11 patients were studied in an uncontrolled manner. CONCLUSIONS: The pulley method seems to facilitate en bloc ESD of early-stage gastric cancers >20 mm. PMID- 21030019 TI - EUS-guided Nd:YAG laser ablation of a hepatocellular carcinoma in the caudate lobe. PMID- 21030020 TI - Use of the shock index to predict ruptured ectopic pregnancies. PMID- 21030021 TI - Action research studies in the intensive care setting: a systematic review. AB - OBJECTIVES: To review published studies using action research in the intensive care unit (ICU) in order to provide an intervention framework to improve clinical outcomes. DESIGN: Systematic review. METHODS: Searches of the electronic databases: Cumulative Index of Nursing and Allied Health Literature (CINAHL); Scopus, Medline, Embase, PsycINFO, and the World Wide Web were undertaken using MeSH key words including: 'action research'; 'health care research', 'health services evaluation'; 'intensive care unit'. Reference lists of retrieved articles was also undertaken to identify further articles. All studies were reviewed by two authors using a critical appraisal tool. RESULTS: The search strategy generated 195 articles. Only 21 studies projects were identified using action research in the ICU. The majority of studies were conducted in the United Kingdom. The participants in the action research studies ranged from 6 to 253. Predominately studies using action research involved nurses in collaboration with patients and family and other health care practitioners to address identified problems in the ICU. CONCLUSIONS: Based on this review it appears that action research is a promising methodological approach to address clinical practice improvement in the ICU. Studies retrieved focussed primarily on process and formative evaluation but not on clinical outcomes. There is a need to incorporate outcome assessment in action research in the ICU to increase the framework of action research to improve clinical outcomes. PMID- 21030023 TI - Does the personal lift-assist device affect the local dynamic stability of the spine during lifting? AB - The personal lift-assist device (PLAD) is an on-body ergonomic aid that reduces low back physical demands through the restorative moment of an external spring element, which possesses a mechanical advantage over the erector spinae. Although the PLAD has proven effective at reducing low back muscular demand, spinal moments, and localized muscular fatigue during laboratory and industrial tasks, the effects of the device on the neuromuscular control of spinal stability during lifting have yet to be assessed. Thirty healthy subjects (15M, 15F) performed repetitive lifting for three minutes, at a rate of 10 lifts per minute, with and without the PLAD. Maximum finite-time Lyapunov exponents, representing short-term (lambda(max-s)) and long-term (lambda(max-l)) divergence were calculated from the measured trunk kinematics to estimate the local dynamic stability of the lumbar spine. Using a mixed-design repeated-measures ANOVA, it was determined that wearing the PLAD did not significantly change lambda(max-s) (MU(NP)=0.335, MU(P)=0.321, p=0.225), but did significantly reduce lambda(max-l) (MU(NP)=0.0024, MU(P)=-0.0011, p=0.014, eta(2)=0.197). There were no between-subject effects of sex, or significant interactions (p>0.720). The present results indicated that lambda(max-s) was not statistically different between the device conditions, but that the PLAD significantly reduced lambda(max-l) to a negative (stable) value. This shows that subjects' neuromuscular systems were able to respond to local perturbations more effectively when wearing the device, reflecting a more stable control of spinal movements. These findings are important when recommending the PLAD for long-term industrial or clinical use. PMID- 21030022 TI - Two adjacent domains (141-150 and 151-160) of apoE covalently linked to a class A amphipathic helical peptide exhibit opposite atherogenic effects. AB - OBJECTIVE: We recently described anti-atherogenic properties of the dual domain peptide Ac-hE18A-NH(2) derived by covalently linking the heparin binding domain 141-150 of apoE to 18A, a class A amphipathic helical peptide. In this paper we have compared the properties of Ac-hE18A-NH(2) with the non-heparin binding 151 160 region of apoE linked to 18A (Ac-nhE18A-NH(2)). METHODS AND RESULTS: Both peptides were highly helical in solution and in association with lipids. Ac-hE18A NH(2) and not Ac-nhE18A-NH(2) enhanced uptake of low density lipoprotein (LDL) in HepG2 cells. While Ac-hE18A-NH(2) retarded the electrophoretic mobility of LDL, Ac-nhE18A-NH(2) slightly enhanced mobility. Ac-hE18A-NH(2) reduced monocyte association with endothelial cells, while Ac-nhE18A-NH(2) increased it. Ac-hE18A NH(2) also reduced lipid hydroperoxide content of LDL while Ac-nhE18A-NH(2) increased it. A single administration of Ac-hE18A-NH(2) (100 MUg/mouse) into apoE null mice dramatically reduced cholesterol (from 600 mg/dL to 180 mg/dL at 5 min and to 60 mg/dL at 5h) while Ac-nhE18A-NH(2) had no effect. Administration (100 MUg/mouse/day, three days a week) into apoE null mice for six weeks showed Ac hE18A-NH(2) group having a moderate aortic sinus lesion reduction compared with the control group (-15.1%), while the Ac-nhE18A-NH(2) administered group had increased lesion area (+33.0% vs controls and 36.1% vs Ac-hE18A-NH(2)). Plasma from mice administered Ac-hE18A-NH(2) for six weeks showed a significant reduction in plasma cholesterol and triglyceride levels and increase in paraoxonase-1 (PON-1) activity compared to controls, while Ac-nhE18A-NH(2) caused no change in plasma cholesterol and decreased PON-1 activity. CONCLUSION: It is proposed that Ac-hE18A-NH(2) reduced lesion progression in apoE null mice due to its anti-inflammatory and lipoprotein clearing properties, while Ac-nhE18A-NH(2) exhibited pro-atherogenic effects. PMID- 21030024 TI - Ultrasound echo is related to stress and strain in tendon. AB - The mechanical behavior of tendons has been well studied in vitro. A noninvasive method to acquire mechanical data would be highly beneficial. Elastography has been a promising method of gathering in vivo tissue mechanical behavior, but it has inherent limitations. This study presents acoustoelasticity as an alternative ultrasound-based method of measuring tendon stress and strain by reporting a relationship between ultrasonic echo intensity (B-mode ultrasound image brightness) and mechanical behavior of tendon in vitro. Porcine digital flexor tendons were cyclically loaded in a mechanical testing system while an ultrasonic echo response was recorded. We report that echo intensity closely follows the applied cyclic strain pattern in time with higher strain protocols resulting in larger echo intensity changes. We also report that echo intensity is related nonlinearly to stress and nearly linearly to strain. This indicates that ultrasonic echo intensity is related to the mechanical behavior in a loaded tissue by an acoustoelastic response, as previously described in homogeneous, nearly incompressible materials. Acoustoelasticity is therefore able to relate strain-dependent stiffness and stress to the reflected echo, even in the processed B-mode signals reflected from viscoelastic and inhomogeneous material such as tendon, and is a promising metric to acquire in vivo mechanical data noninvasively. PMID- 21030025 TI - Regarding fixed ring and floating ring pure moment application. PMID- 21030026 TI - A new chromatographic response function for use in size-exclusion chromatography optimization strategies: Application to complex organic mixtures. AB - A new chromatographic response function (CRF) is presented aiming at designing an optimal chromatographic separation protocol for assessing the molecular size distribution of complex organic mixtures, such as those of natural organic matter from different sources (atmospheric, aqueous, and terrestrial). This CRF can be applied to mixtures of unknown solutes, being well suited for describing separation processes of pair of peaks of highly unequal area, and also for overlapping and asymmetric peaks. The performance of the developed CRF was compared to that of an existing response function, using simulated chromatograms. The capability of the new function to qualify the resolution degree that it is attained under different chromatographic conditions was further assessed through a size-exclusion chromatography study of a variety of different organic compounds, via a two-level full factorial design. It was proved that this function is a reliable alternative to optimize simultaneously the composition of the mobile phase (pH, ionic strength, and organic modifier concentration) and the instrumental variables (flow rate). PMID- 21030027 TI - Sub-1-micron mesoporous silica particles functionalized with cyclodextrin derivative for rapid enantioseparations on ultra-high pressure liquid chromatography. AB - Mesoporous silica particles of relatively uniform sub-1-micron size (0.6-0.9 MUm) were successfully prepared by a modified synthesis strategy and applied in chiral separation in an ultra-high pressure liquid chromatography system. These particles were prepared via a ternary surfactant system (Pluronic P123, F127 and hexadecyltrimethyl-ammonium bromide) and subsequently derivatized with perphenylcarbamoylated-beta-cyclodextrin moieties. The mesoporous silica particles, despite their submicron size, enabled low back-pressure operation on an ultra-high pressure liquid chromatography system at a maximum flow rate of 2 ml/min. In addition, the particles possessed high surface area (480 m(2)/g) and thus afforded high cyclodextrin derivative loading (32 MUmol/g), demonstrating rapid enantioseparation and good resolution of 6 basic and neutral racemates. PMID- 21030028 TI - Particle-packed column versus silica-based monolithic column for liquid chromatography-electrospray-linear ion trap-tandem mass spectrometry multiallergen trace analysis in foods. AB - A bicarbonate buffer-based extraction method for the simultaneous analysis of five nut allergens (Ana o 2, cashew-nut; Cor a 9, hazelnut; Pru 1, almond; Ara h3/4, peanut; Jug r 4, walnut) in cereals and biscuits using liquid chromatography-electrospray-linear ion trap-tandem mass spectrometry (LC-ESI-LIT MS(2)) was developed and validated. The method was based on our earlier published LC-MS(2)-based method in a research frame aimed at the identification and determination of hidden allergens in foods by using selective biomarker peptides. A C18 particle-packed column and a silica-based C18 monolithic column were compared in terms of chromatographic performances, such as peak shape, resolution, analysis time and selectivity. The C18 particle-packed column exhibited better performances and was further used for method development and validation. By operating under MS(2) selected reaction monitoring (SRM) acquisition mode, linearity, limits of detection (LOD) and quantitation, trueness and precision were evaluated on breakfast samples enriched with a mix of the five nuts. Good linearity of the matrix matched-calibration curves was obtained and detection limit values generally varied from 14 to 55 mg nut/kg matrix. Recoveries were in the 76+/-4% to 94+/-3% range with RSD <15%. The capabilities of LIT to perform MS(n) fragmentation was exploited to improve selectivity of the analysis, and the LC-(SRM) MS(2) method was compared in terms of LOD, linearity, precision and accuracy with a LC-(SRM) MS(3) method. Finally, both the LC-MS(2) and LC-MS(3) methods were successfully applied to the analysis of nut traces in commercially available breakfast cereals and biscuits. PMID- 21030029 TI - Evaluation on the performance of four different column models mounted on the compact type-I coil planet centrifuge. AB - Optimal positions of coiled separation columns on the type-I centrifuge were determined for four typical two-phase solvent systems to obtain the best separation efficiency (resolution and retention of stationary phase) for each with a suitable set of test samples. A set of short coiled columns is connected in series and mounted around the holder hub in four different ways: (model A) the tail of one unit with left-handedness was connected to the head of the next unit with right-handedness (TL-HR); (model B) the tail of one unit with left handedness was connected to the tail of the next unit with right-handedness (TL TR); (model C) the tail of one unit with left-handedness was connected to the tail of the next unit with left-handedness (TL-TL); (model D) the tail of one unit with left-handedness was connected to the head of the next unit with left handedness (TL-HL). The results indicated that the performance of model D was the best among the four models. High revolution speed (800 rpm) is favorable to separation using the moderately hydrophobic solvent system of hexane-ethyl acetate-methanol-0.1M HCl (1:1:1:1, v/v) (HEMW), while lower revolution speed (600 rpm) is beneficial to the separation with polar solvent system of 1-butanol acetic acid-water (19:1:20, v/v) (BAW). PMID- 21030031 TI - Optimization of two methods for the analysis of hydrogen peroxide: high performance liquid chromatography with fluorescence detection and high performance liquid chromatography with electrochemical detection in direct current mode. AB - Two complementary methods were optimized for the separation and detection of trace levels of hydrogen peroxide. The first method utilized reversed-phase high performance liquid chromatography with fluorescence detection (HPLC-FD). With this approach, hydrogen peroxide was detected based upon its participation in the hemin-catalyzed oxidation of p-hydroxyphenylacetic acid to yield the fluorescent dimer. The second method utilized high performance liquid chromatography with electrochemical detection (HPLC-ED). With this approach, hydrogen peroxide was detected based upon its oxidation at a gold working electrode at an applied potential of 400 mV vs. hydrogen reference electrode (Pd/H(2)). Both methods were linear across the range of 15-300 MUM, and the electrochemical method was linear across a wider range of 7.4-15,000 MUM. The limit of detection for hydrogen peroxide was 6 MUM by HPLC/FD, and 0.6 MUM by HPLC/ED. A series of organic peroxides and inorganic ions were evaluated for their potential to interfere with the detection of hydrogen peroxide. Studies investigating the recovery of hydrogen peroxide with three different extraction protocols were also performed. Post-blast debris from the detonation of a mixture of concentrated hydrogen peroxide with nitromethane was analyzed on both systems. Hydrogen peroxide residues were successfully detected on this post-blast debris. PMID- 21030030 TI - A replaceable microreactor for on-line protein digestion in a two-dimensional capillary electrophoresis system with tandem mass spectrometry detection. AB - We describe a two-dimensional capillary electrophoresis system that incorporates a replaceable enzymatic microreactor for on-line protein digestion. In this system, trypsin is immobilized on magnetic beads. At the start of each experiment, old beads are flushed to waste and replaced with a fresh plug of beads, which is captured by a pair of magnets at the distal tip of the first capillary. For analysis, proteins are separated in the first capillary. A fraction is then parked in the reactor to create peptides. Digested peptides are periodically transferred to the second capillary for separation; a fresh protein fraction is simultaneously moved to the reactor for digestion. An electrospray interface is used to introduce peptides into a mass spectrometer for analysis. This procedure is repeated for several dozen fractions under computer control. The system was demonstrated by the separation and digestion of insulin chain b oxidized and beta-casein as model proteins. PMID- 21030032 TI - pH transients in hydroxyapatite chromatography columns-Effects of operating conditions and media properties. AB - pH transitions occur in hydroxyapatite (HAP) columns that are subject to step changes in salt concentration, which have been shown to be controlled by proton exchange on the HAP surface. The pH temporarily decreases before gradually returning to the feed value when the salt concentration increases, potentially compromising the stability of the HAP when either the magnitude or duration of the pH drop is excessive. The opposite happens when the salt concentration decreases. In this work we address the effects of several key variables: the flow rate, the particle size, the use of salt gradients instead of steps, the use of different co-buffers, the surface area of the HAP, and the use of a slightly alkaline wash prior to increasing the salt concentration. Flow rate and particle size were found to have virtually no effect, demonstrating that the pH transitions are equilibrium rather than kinetically driven. Salt gradients resulted in smaller pH drops compared to steps since the exchanged protons are diluted over the gradient volume. MES and histidine used as co-buffers were effective at reducing the duration of the pH transitions but did not affect their magnitude. The same result was found when comparing HAP samples with different surface areas, with the lower surface area HAP yielding much shorter duration but similar pH drops and rises. Finally, washing the HAP column with a pH 7.5 buffer prior to the salt step was found to dramatically reduce the subsequent pH drop. In general, there was good agreement between these results and predictions based on our previously developed model. PMID- 21030033 TI - Characterization and quantification of Sm(III)/ and Cm(III)/clay mineral outer sphere species by TRLFS in D2O and EXAFS studies. AB - In order to assess the long-term safety of deep radioactive waste repositories, a precise characterization of the different sorption processes on a molecular basis and the exact definition of geochemical boundary conditions for their relevance are of immense importance. Through sorption on various minerals the migration of radionuclides will be hindered and their retention will be ensured. Using time resolved laser fluorescence spectroscopy (TRLFS) and extended X-ray absorption fine structure (EXAFS) spectroscopy, it was possible to identify outer-sphere sorbed trivalent lanthanides and actinides onto different montmorillonites and illite. Furthermore, the quantification of Cm(III)/clay outer-sphere sorption in D(2)O at different ionic strengths was shown. The results were confirmed by ion exchange model calculations. Finally, the structural parameters of a Sm(III)/clay outer-sphere complex were obtained by EXAFS measurements. PMID- 21030034 TI - Charge regulation enables anionic hydroxypropyl guar-borate adsorption onto anionic and cationic polystyrene latex. AB - Reported are adsorption isotherms for guar and hydroxypropyl guar (HPG), with and without the presence of borate ions, onto surfactant free anionic polystyrene latex. Guar and HPG formed adsorbed monolayers on the hydrophobic latex. The presence of borate ions converted the nonionic guar and HPG into an anionic polyelectrolyte. However, there was no measurable influence of bound borate ions on the adsorption of guar or HPG onto anionic, hydrophobic latex. To underscore the unusual behavior of HPG-borate, a sample of HPG was oxidized to introduce carboxyl groups, and the adsorption of the carboxylated HPG onto anionic polystyrene was measured. Unlike HPG-borate, oxidized HPG did not adsorb onto negative polystyrene latex at neutral pH because of electrostatic repulsion. To explain the adsorption of negative HPG-borate onto negative latex, we proposed that as HPG-borate segments approach the latex surface, the negative electrostatic potential near the latex surface induces the detachment of the labile borate groups from HPG. PMID- 21030035 TI - Oral food challenges in children with a diagnosis of food allergy. AB - OBJECTIVE: To assess the outcome of oral food challenges in patients placed on elimination diets based primarily on positive serum immunoglobulin E (IgE) immunoassay results. STUDY DESIGN: This is a retrospective chart review of 125 children aged 1-19 years (median age, 4 years) evaluated between January 2007 and August 2008 for IgE-mediated food allergy at National Jewish Health and who underwent an oral food challenge. Clinical history, prick skin test results, and serum allergen-specific IgE test results were obtained. RESULTS: The data were summarized for food avoidance and oral food challenge results. Depending on the reason for avoidance, 84%-93% of the foods being avoided were returned to the diet after an oral food challenge, indicating that the vast majority of foods that had been restricted could be tolerated at discharge. CONCLUSIONS: In the absence of anaphylaxis, the primary reliance on serum food-specific IgE testing to determine the need for a food elimination diet is not sufficient, especially in children with atopic dermatitis. In those circumstances, oral food challenges may be indicated to confirm food allergy status. PMID- 21030036 TI - Growth hormone excess in children with neurofibromatosis type 1-associated and sporadic optic pathway tumors. AB - OBJECTIVE: To describe the clinical manifestations of growth hormone (GH) excess in children with optic pathway tumors (OPT). STUDY DESIGN: Descriptive case series of 5 children with OPT, 3 with associated neurofibromatosis type 1, referred for evaluation of accelerated linear growth. GH excess was evaluated by oral glucose tolerance tests with frequent sampling of GH levels. Precocious puberty was evaluated by basal luteinizing hormone and sex steroid hormone levels. Stimulation testing with leuprolide acetate (20 MUg/kg subcutaneously) was conducted in patients with normal baseline testing. RESULTS: All patients had OPT involving both the hypothalamus and optic chiasm. All patients had elevated levels of the growth factor insulin-like growth factor 1 and on stimulation testing demonstrated an inability to suppress GH levels to < 1.0 ng/mL, indicating the presence of unregulated GH secretion. Additionally, all patients displayed biochemical evidence of precocious puberty. CONCLUSIONS: GH excess may be an under-recognized occurrence in the setting of neurofibromatosis type 1 and OPT. GH excess in such patients may contribute to continued brain tumor growth. Given the potential adverse consequences of unrestrained GH excess, all children with chiasmal or hypothalamic tumors who have rapid growth should be evaluated for both precocious puberty and GH excess. PMID- 21030037 TI - Tetrahydrobiopterin and PKU: into the future. PMID- 21030038 TI - Serologically defined human metapneumovirus in pediatric community-acquired pneumonia. PMID- 21030039 TI - Histone deacetylase inhibitor potentiates anticancer effect of docetaxel via modulation of Bcl-2 family proteins and tubulin in hormone refractory prostate cancer cells. AB - PURPOSE: We evaluated the antitumor effects of docetaxel (Sigma(r)) and histone deacetylase inhibitors in hormone refractory prostate cancer cells, and analyzed the mechanism by which combination treatment induced cell death. MATERIALS AND METHODS: We used LNCaP, DU145 and PC3 cells (ATCC(r)) to evaluate the in vitro apoptotic effects of histone deacetylase inhibitors and their combinations with docetaxel as well as the molecular mechanisms. The DU145 xenograft model was used to evaluate the in vivo efficacy of PXD101 combined with docetaxel. RESULTS: Suberoylanilide hydroxamic acid or PXD101 inhibited the growth of hormone dependent LNCaP cells, and hormone independent DU145 and PC3 cells. It increased sub-G1 population and activated caspase-8, 9 and 3, indicating apoptosis induction. Pretreating DU145 cells with docetaxel followed by histone deacetylase inhibitors showed significant synergistic cytotoxicity compared with that of simultaneous co-treatment or reverse sequential treatment. Pretreatment with docetaxel followed by histone deacetylase inhibitors increased the apoptotic sub G1 population, caspase activation and tubulin acetylation compared with that of docetaxel alone. Combination treatment decreased Mcl-1 and Bcl-xl, and increased t-Bid, Bik and Bim. Combined docetaxel and PXD101 reduced tumor size with efficacy equivalent to that of a double dose of docetaxel alone in the DU145 xenograft model. CONCLUSIONS: These preclinical results indicate that the sequential combination of docetaxel and histone deacetylase inhibitors led to a synergistic increase in the death of hormone refractory prostate cancer cells via intrinsic and extrinsic apoptotic pathways by modulating Bcl-2 family proteins and tubulin in vitro and in vivo. Results suggest that this combination may be a new therapeutic modality in patients with hormone refractory prostate cancer. PMID- 21030040 TI - Receptor mediated agglutination of human spermatozoa by spermagglutinating factor isolated from Staphylococcus aureus. AB - PURPOSE: We examined spermagglutinating factor isolated from Staphylococcus aureus for evidence of receptor mediated agglutination of human spermatozoa. MATERIALS AND METHODS: Binding to spermatozoa by spermagglutinating factor isolated from S. aureus with a high degree of specificity indicates receptor ligand interaction. To examine this interaction we isolated and purified the ligand and the receptor. To assess receptor mediated agglutination of spermatozoa further we blocked spermagglutination induced by spermagglutinating factor in the presence of receptor. RESULTS: Spermagglutinating factor induced spermagglutination was competitively inhibited by adding purified receptor, indicating that sperm agglutinating factor isolated from S. aureus attaches to specific receptors on human spermatozoa. The spermagglutinating factor receptor was a protein with a molecular weight of approximately 57 kDa. Spermagglutinating factor induced spermagglutination and at higher concentrations had a spermicidal effect, which was inhibited by introducing the receptor. As observed on scanning electron microscopy studies, incubating spermatozoa with spermagglutinating factor showed profound morphological alterations. However, spermatozoa with normal morphology were noted when incubated with spermagglutinating factor in the presence of receptor, indicating that morphological alterations may account for spermatozoa agglutination by spermagglutinating factor. CONCLUSIONS: Results suggest that spermagglutinating factor isolated from S. aureus may bind specifically to sperm surface receptor sites before causing spermagglutination. PMID- 21030041 TI - Cirrhosis with microscopic hematuria and pelvic congestion syndrome. PMID- 21030043 TI - Immunohistochemical expression of muscarinic receptors in the urothelium and suburothelium of neurogenic and idiopathic overactive human bladders, and changes with botulinum neurotoxin administration. AB - PURPOSE: To investigate the possible associations of urothelial and suburothelial muscarinic receptors with human bladder pathophysiology we examined the immunohistochemical expression of muscarinic receptors types 1, 2 and 3 in the bladder urothelium and suburothelium of patients with neurogenic or idiopathic detrusor overactivity compared with that in controls. We also examined associations with patient quantified symptoms and the effect of intradetrusor botulinum neurotoxin type A treatment. MATERIALS AND METHODS: We obtained bladder biopsies from 36 patients with detrusor overactivity before, and 4 and 16 weeks after treatment with intradetrusor botulinum neurotoxin type A via flexible cystoscopy. Patients with neurogenic detrusor overactivity were injected with 300 U botulinum neurotoxin type A and those with idiopathic detrusor overactivity received 200 U. Control biopsies were taken from 7 patients during investigation for asymptomatic microscopic hematuria. We studied muscarinic receptor immunohistochemical expression using commercial antibodies to muscarinic receptors 1, 2 and 3 with results quantified by image analysis. RESULTS: We noted decreased suburothelial muscarinic receptor immunoreactivity in detrusor overactivity biopsies vs controls, which were significant for muscarinic receptors 1 and 3. After successful botulinum neurotoxin treatment we noted only increased muscarinic receptor 1 and 2 immunoreactivity. Urothelial muscarinic receptor 1 and 3 immunoreactivity was increased after treatment. We identified no substantial urothelial muscarinic receptor 2 immunoreactivity. Receptor levels showed inverse correlations with patient urgency and frequency. CONCLUSIONS: Decreased muscarinic receptor levels in the urothelium and suburothelium of patients with detrusor overactivity were largely restored to control levels after successful treatment with botulinum neurotoxin type A. Correlations of receptor levels with patient symptoms further support a role for urothelial and suburothelial muscarinic receptors in detrusor overactivity in humans. PMID- 21030042 TI - Silver or nitrofurazone impregnation of urinary catheters has a minimal effect on uropathogen adherence. AB - PURPOSE: Bacterial adherence to the urinary catheter is an early step in biofilm formation and the pathogenesis of catheter associated urinary tract infection. We studied in vitro the effect of silver or nitrofurazone impregnation of urinary catheters on uropathogen ability to adhere to urinary catheters. MATERIALS AND METHODS: We studied commercially available nitrofurazone-silicone, silicone only, silver-silicone-hydrogel, silicone-hydrogel, silver-latex-hydrogel and latex hydrogel catheters. Catheters were incubated in sterile broth for 0, 3, 5, 7 and 10 days, respectively, before inoculation and overnight incubation with Escherichia coli or Enterococcus faecalis. RESULTS: Adherence of E. coli and E. faecalis to nitrofurazone catheters was significantly decreased compared to that of silicone-only catheters when catheters were fresh. The anti-adherence effect of nitrofurazone on E. coli decreased with time but was still significant at 5 days. For E. faecalis the effect of nitrofurazone was lost by 3 days of pre incubation. E. coli adherence was not significantly decreased on silver impregnated catheters compared to that on control catheters of the same base material. Silver was associated with a significant decrease in E. faecalis adherence to latex-hydrogel catheters but not to silicone-hydrogel catheters. The adherence of each species to silicone catheters with hydrogel was significantly lower than that to silicone-only control catheters. CONCLUSIONS: Silver impregnation had little effect on bacterial adherence in our model and nitrofurazone impregnation had a significant effect only for the first 5 days. Our results do not support a role for silver urinary catheters to prevent catheter associated urinary tract infection by decreasing bacterial adherence. PMID- 21030044 TI - Mechanism of synergistic antitumor effect of sorafenib and interferon-alpha on treatment of renal cell carcinoma. AB - PURPOSE: The multikinase and tyrosine kinase inhibitor sorafenib has antitumor activity in patients with advanced renal cell carcinoma. Recent reports show the ability of sorafenib to synergize with interferon-alpha, leading to greater antitumor activity. We examined the underlying mechanism of sorafenib and interferon-alpha synergism for renal cell carcinoma treatment in vitro and in tumor bearing murine models. MATERIALS AND METHODS: We used murine and human renal cell carcinoma cell lines for in vitro cell proliferation assay. ACHN (ATCC(r)) and RENCA tumors were subcutaneously transplanted into NCr-nu/nu and syngeneic BALB/c mice (Charles River Laboratories, Yokohama, Japan), respectively. Mice were treated with sorafenib and/or interferon-alpha, and tumor growth was monitored. Immunological assays were done in the RENCA model. RESULTS: In the ACHN and RENCA cell lines combination index analysis clearly revealed the synergistic antiproliferative effects of interferon-alpha and sorafenib in vitro. In the ACHN NCr-nu/nu model we clearly noted the synergistic antitumor effects of interferon-alpha and sorafenib, indicating the synergistic direct effects of each drug on tumor growth. In the RENCA BALB/c model flow cytometry showed no change in the proportion of lymphocytes. However, while sorafenib alone did not induce natural killer or cytotoxic T-lymphocyte activity against RENCA in that model, interferon-alpha alone or combined with sorafenib induced natural killer and cytotoxic T-lymphocyte activity. CONCLUSIONS: Our results show the synergistic activity of interferon-alpha and sorafenib. These findings provided the rationale for combination therapy with interferon-alpha and sorafenib in patients with advanced renal cell carcinoma. PMID- 21030045 TI - The immunocytokine F8-IL2 improves the therapeutic performance of sunitinib in a mouse model of renal cell carcinoma. AB - PURPOSE: We investigated the therapeutic action of F8-IL2, a fusion protein consisting of the F8 antibody specific to the alternatively spliced extradomain-A of fibronectin, in diabody format and of human interleukin-2 in the Caki-1 (ATCC(r)) model of human renal cell carcinoma grafted subcutaneously in nude mice. MATERIALS AND METHODS: F8-IL2 was cloned, expressed in CHO cells and purified to homogeneity. This immunocytokine was administered alone or combined with 3 standard drugs commonly used as therapy for kidney cancer, including sunitinib, sorafenib and interferon-alpha, in 2 sets of doses and treatment schedules. RESULTS: Neither F8-IL2 nor any other therapeutic agent cured tumor bearing mice when used as a single agent. The best therapeutic results were observed for the combination of sunitinib with F8-IL2 in a continuous administration schedule, which yielded a 28% cure rate and substantial tumor growth retardation. CONCLUSIONS: Considering that recombinant interleukin-2 based immunocytokines are now being investigated in several clinical trials in patients with cancer alone or combined with chemotherapy our preclinical results provide a motivation to study F8-IL2 combined with sunitinib in clinical trials in patients with kidney cancer. PMID- 21030047 TI - In vitro activity of available antimicrobial coated Foley catheters against Escherichia coli, including strains resistant to extended spectrum cephalosporins. AB - PURPOSE: We determined the activity, comparative potency and effect durability of commercially available, antimicrobial coated Foley catheters against Escherichia coli isolates, including extended spectrum cephalosporin resistant strains. MATERIALS AND METHODS: We used an inhibition zone assay (diffusible inhibition) and an adherence assay (diffusible and contact dependent inhibition) to assess the inhibitory effect of 3 currently marketed antimicrobial coated catheters, including 2 coated with silver and 1 coated with nitrofurazone, and corresponding silicone catheters against 9 E. coli strains, including 7 extended spectrum cephalosporin resistant and 2 extended spectrum cephalosporin susceptible strains, and a Pseudomonas aeruginosa reference strain. RESULTS: In each assay the nitrofurazone coated catheter showed the greatest and most durable (through day 5) inhibitory activity. This was comparable for extended spectrum cephalosporin resistant and extended spectrum cephalosporin susceptible E. coli strains but decreased or absent for the Pseudomonas strain. One of the 2 silver coated catheters showed sparse but measurable inhibition zone activity on day 1 but not thereafter and no statistically significant activity on adherence assay. The other lacked detectable activity using either test system. In the adherence assay the nitrofurazone coated catheter decreased the E. coli count as potently in inoculum broths as in post-sonication suspensions (median decrease more than 8 and more than 6 log(10) cfu/ml, respectively). CONCLUSIONS: The nitrofurazone coated catheter showed significantly greater in vitro potency and durability of the antimicrobial effect against 9 E. coli strains than the 2 silver coated catheters, of which 1 appeared completely inert. No difference in antimicrobial effect was apparent between extended spectrum cephalosporin resistant and susceptible E. coli. The clinical relevance of these in vitro findings remains to be defined. PMID- 21030048 TI - Editorial comment. PMID- 21030049 TI - Tonsillectomy does not improve bedwetting: results of a prospective controlled trial. AB - PURPOSE: Sleep disordered breathing caused by tonsillar hypertrophy has been implicated as a cause of primary and secondary nocturnal enuresis in children. We prospectively studied the preoperative and postoperative rates of nocturnal and daytime incontinence in a group of children with tonsillar hypertrophy undergoing tonsillectomy compared to a matched control group undergoing surgery unrelated to the airway or urinary tract. MATERIALS AND METHODS: A total of 326 toilet trained children 3 to 15 years old were included, with 257 in the tonsillectomy group and 69 in the control group. Severity of tonsillar hypertrophy was graded preoperatively on a scale of 1 to 4. A voiding questionnaire regarding number of bedwetting and daytime incontinence episodes per week, voids per day, bowel movements per week, secondary or primary enuresis and family history was completed by parents preoperatively, and at 3 and 6 months postoperatively. RESULTS: Preoperatively the respective rates of nocturnal enuresis and daytime incontinence were 33% and 17% in the tonsillectomy group (p=0.89), and 35% and 14% in the control group (p=0.3). The respective cure rates for bedwetting at 3 and 6 months postoperatively were 40% and 50% in the tonsillectomy group (p=0.60), and 35% and 48% in the control group (p=0.61). Similarly no difference was seen in improvement or cure of daytime incontinence at 3 and 6 months postoperatively. CONCLUSIONS: We found no association between tonsillar hypertrophy and urinary incontinence before or after tonsillectomy. PMID- 21030051 TI - Nephrogenic adenoma of the bladder. PMID- 21030052 TI - Occurrence, distribution and characteristics of beached plastic production pellets on the island of Malta (central Mediterranean). AB - The distribution, abundance and chemical characteristics of plastic production pellets on beaches of the island of Malta have been determined. Pellets were observed at all locations visited and were generally most abundant (> 1000m-2 at the surface) on the backshores of beaches with a westerly aspect. Most pellets were disc-shaped or flattened cylinders and could be categorised as white, yellow, amber or brown. The polymeric matrix of all pellets analysed by infrared spectroscopy was polyethylene and the degree of yellowing or darkening was associated with an increase in the carbonyl index, hence extent of photo oxidation or aging. Qualitatively, pellets are similar to those reported for other regions of the Mediterranean in surveys spanning three decades, suggesting that they are a general and persistent characteristic of the region. PMID- 21030053 TI - A feruloyltyramine trimer isolated from potato common scab lesions. AB - (1)H NMR analysis established that a potential suberin intermediate isolated from potato common scab lesions contained three O-methyl groups, a phenylcoumaran-type linkage and a conjugated trans double bond. Mass spectral data determined its molecular formula as indicative of a dehydrotrimer structure formed from three feruloyltyramine units. (1)H and (13)C NMR correlation studies supported the structure as that of a grossamide unit (3) linked through its double bond to the feruloyl phenolic of a third feruloyltyramine group. Identification of the feruloyltyramine trimer (4) expands the number of cross-linked intermediates potentially involved in the suberization process and highlights the presence of a second type of inter-unit linkage available for synthesis of the poly-phenolic domains. PMID- 21030054 TI - Pterocarpenes elicited by Aspergillus caelatus in peanut (Arachis hypogaea) seeds. AB - The substituted pterocarpenes named aracarpene-1 (1) and aracarpene-2 (2) were isolated from wounded peanut seeds challenged by a strain of Aspergillus caelatus. The structures of these putative phytoalexins were determined by interpretation of NMR and MS data. The aracarpenes were investigated for their antifungal and antibacterial activities as well as antioxidant, anti inflammatory, and cytotoxic activities in mammalian cells. Aracarpene-2 demonstrated high antibacterial properties against tested gram-positive and gram negative bacteria, whereas aracarpene-1 displayed low antibacterial properties against the same bacteria. Both compounds had no antifungal activity against Aspergillus flavus. Together with peanut stilbenoids that are also produced in the challenged seeds, these compounds may represent a class of low-molecular weight peanut metabolites with a defensive role(s) against pathogenic microorganisms. PMID- 21030055 TI - Cigarette characteristic and emission variations across high-, middle- and low income countries. AB - OBJECTIVES: The public health burden of tobacco use is shifting to the developing world, and the tobacco industry may apply some of its successful marketing tactics, such as allaying health concerns with product modifications. This study used standard smoking machine tests to examine the extent to which the industry is introducing engineering features that reduce tar and nicotine to cigarettes sold in middle- and low-income countries. STUDY DESIGN: Multicountry observational study. METHODS: Cigarettes from 10 different countries were purchased in 2005 and 2007 with low-, middle- and high-income countries identified using the World Bank's per capita gross national income metric. Physical measurements of each brand were tested, and tobacco moisture and weight, paper porosity, filter ventilation and pressure drop were analysed. Tar, nicotine and carbon monoxide emission levels were determined for each brand using International Organization for Standardization and Canadian Intensive methods. Statistical analyses were performed using Statistical Package for the Social Sciences. RESULTS: Among cigarette brands with filters, more brands were ventilated in high-income countries compared with middle- and low-income countries [chi(2)(4)=25.92, P<0.001]. Low-income brands differed from high- and middle-income brands in engineering features such as filter density, ventilation and paper porosity, while tobacco weight and density measures separated the middle- and high-income groups. Smoke emissions differed across income groups, but these differences were largely negated when one accounted for design features. CONCLUSIONS: This study showed that as a country's income level increases, cigarettes become more highly engineered and the emissions levels decrease. In order to reduce the burden of tobacco-related disease and further effective product regulation, health officials must understand cigarette design and function within and between countries. PMID- 21030056 TI - Gene expression of endothelin-1 and its receptors in the heart of broiler chickens with T(3)-induced pulmonary hypertension. AB - To investigate the effect of T(3)-induced pulmonary hypertension on endothelin (ET) production and genes expression of ET-1, ET(A) and ET(B) receptors (ET(A)R and ET(B)R) during rearing, semiquantitative RT-PCR and enzyme immunometric assay were performed in the heart ventricles and serum, respectively. The ET-1 and its receptor genes were expressed in the right and left ventricles of control and T(3)-treated broilers at 12, 28 and 49 days of age. There were significant (P<0.05) reductions of the relative amounts of ET-1 (in both ventricles) and ET(A)R (in the right ventricle) mRNAs at 28 and 49 days of age, in T(3)-treated broilers compared to controls. The relative amounts of ET(B)R mRNA in the right and left ventricles did not significantly differ between control and T(3)-treated broilers at any age. The serum level of ET was significantly (P<0.05) increased in T(3)-treated chickens at 28 and 49 days of age when compared with that of the control. It is concluded that ET-1, ET(A)R and ET(B)R genes are normally expressed in the heart ventricles of broilers. It is likely that increased serum level of ET and decreased ET-1/ET(A)R genes expression in the ventricles are involved in the heart dysfunction of broiler chickens with developmental pulmonary hypertension. PMID- 21030057 TI - Characterization and validation of bovine gonadotripin releasing hormone receptor (GNRHR) polymorphisms. AB - Gonadotropin releasing hormone and its receptor (GNRHR) play a critical role in sexual differentiation and reproduction. Available evidence shows a strong genetic component in the timing of puberty. In bovines, there are significant differences within and among beef breeds in the time when bulls reach puberty. Despite its economic importance, there are not many SNPs or genetic markers associated with this characteristic. The aims of the study were to identify DNA polymorphism in the bovine GNRHR by re-sequencing analysis, determine haplotype phases, and perform a population study in a selected tag SNP in six breeds. Eight SNPs were detected, including: one in the Upstream Regulatory Region (URR), five in the coding regions, and two in non-coding regions. This polymorphism level corresponds to one variant every 249.4bp and a global nucleotide diversity of 0.385. Two haplogroups comprising nine haplotypes and two linkage blocks were detected. Despite 5 tag SNPs were required to capture all variability, just one SNP allowed to define both haplogroups, and only two SNPs were needed to differentiate the most common haplotypes. An additional taq SNP was necessary to identify both URR variants. Allele-frequency analysis of a selected taq SNP among breeds showed a geographical cline. European Bos taurus breeds had lower frequencies of the C allele than B. indicus type cattle, while Creole cattle and Wagyu breeds had intermediate frequency. There was a significant correlation between frequency profile and timing of puberty among the studied breeds, which seems to suggest that genetic variation within bovine GNRHR gene could explain at least part of the reported variability. PMID- 21030058 TI - Capsid protein identification and analysis of mature Triatoma virus (TrV) virions and naturally occurring empty particles. AB - Triatoma virus (TrV) is a non-enveloped +ssRNA virus belonging to the insect virus family Dicistroviridae. Mass spectrometry (MS) and gel electrophoresis were used to detect the previously elusive capsid protein VP4. Its cleavage sites were established by sequencing the N-terminus of the protein precursor and MS, and its stoichiometry with respect to the other major capsid proteins (VP1-3) was found to be 1:1. We also characterized the polypeptides comprising the naturally occurring non-infectious empty capsids, i.e., RNA-free TrV particles. The empty particles were composed of VP0-VP3 plus at least seven additional polypeptides, which were identified as products of the capsid precursor polyprotein. We conclude that VP4 protein appears as a product of RNA encapsidation, and that defective processing of capsid proteins precludes genome encapsidation. PMID- 21030059 TI - Preferential use of RNA leader sequences during influenza A transcription initiation in vivo. AB - In vitro transcription initiation studies revealed a preference of influenza A virus for capped RNA leader sequences with base complementarity to the viral RNA template. Here, these results were verified during an influenza infection in MDCK cells. Alfalfa mosaic virus RNA3 leader sequences mutated in their base complementarity to the viral template, or the nucleotides 5' of potential base pairing residues, were tested for their use either singly or in competition. These analyses revealed that influenza transcriptase is able to use leaders from an exogenous mRNA source with a preference for leaders harboring base complementarity to the 3'-ultimate residues of the viral template, as previously observed during in vitro studies. Internal priming at the 3'-penultimate residue, as well as "prime-and-realign" was observed. The finding that multiple base pairing promotes cap donor selection in vivo, and the earlier observed competitiveness of such molecules in vitro, offers new possibilities for antiviral drug design. PMID- 21030060 TI - Evaluation and modeling of benzalkonium chloride inhibition and biodegradation in activated sludge. AB - The inhibitory effect and biodegradation of benzalkonium chloride (BAC), a mixture of alkyl benzyl dimethyl ammonium chlorides with different alkyl chain lengths, was investigated at a concentration range from 5 to 20 mg/L and different biomass concentrations in an activated sludge system. A solution containing glucose and mineral salts was used as the wastewater in all the assays performed. The inhibition of respiratory enzymes was identified as the mode of action of BAC as a result of oxygen uptake rate analysis performed at BAC concentrations ranging between 5 and 70 mg/L. The glucose degradation in the activated sludge at different BAC and biomass concentrations was well-described with Monod kinetics with competitive inhibition. The half-saturation inhibition constant (K(I)) which is equivalent to EC(50) of BAC for the activated sludge tested ranged between 0.12 and 3.60 mg/L. The high K(I) values were recorded at low BAC-to-biomass ratios, i.e. less than 10 mg BAC/g VSS, at which BAC was almost totally adsorbed to biomass and not bioavailable. BAC degradation started as soon as glucose was totally consumed. Although BAC was almost totally adsorbed on the biomass, it was degraded completely. Therefore, BAC degradation was modeled using two-phase biodegradation kinetics developed in this study. This model involves rapid partitioning of BAC to biomass and consecutive degradation in both aqueous and solid phases. The aqueous phase BAC degradation rate was twenty times, on average, higher than the solid phase degradation rate. The specific aqueous (k(I1)) and solid (k(I2)) phase BAC utilization rate constants were 1.25 and 0.31 mg BAC/g VSS h, respectively. The findings of this study would help to understand the reason of extensive distribution of quaternary ammonium compounds in wastewater treatment plant effluents and in natural water systems although QACs are biodegradable, and develop strategies to avoid their release and accumulation in the environment. PMID- 21030061 TI - Effect of coplanar PCB concentration on dechlorinating microbial communities and dechlorination in estuarine sediments. AB - The effect of concentration of coplanar PCB on the dechlorinating microbial community and dechlorination were investigated in anoxic estuarine sediment collected from Er-Jen River and enriched with 10 and 50 mg L-1 of 3,4,4',5 tetrachlorobiphenyl, 3,3',4,4',5-pentachlorobiphenyl, and 3,3',4,4',5,5' hexachlorobipheny. Dechlorination rates were similar in the cultures enriched with 10 and 50 mg L-1 of 3,4,4',5-tetrachlorobiphenyl, whereas significantly higher dechlorination rates were observed in cultures enriched with 10 mg L-1 of 3,3',4,4',5-pentachlorobiphenyl. No dechlorination was observed in sediment slurries enriched with 3,3',4,4',5,5'-hexachlorobipheny. Para dechlorination occurred prior to meta dechlorination during reductive dechlorination of 3,4,4',5 tetrachlorobiphenyl and 3,3',4,4',5-pentachlorobiphenyl. GC-MS and denaturing gradient gel electrophoresis (DGGE) were used to detect dechlorination products and dechlorinating microorganisms in the enriched sediment cultures during the process of degradation. Two Chloroflexi phylotypes observed in DGGE were responsible for para and meta dechlorination respectively. Phylotype Cp-1 has 98% similarity to uncultured bacterium N5-12. Phylotype Cm-1 has 99% similarity to uncultured dechlorinating bacterium m1 or SF1 belonging to the omicron-17/DF-1 group of PCB-dechlorinating bacteria. PMID- 21030062 TI - Viable skin efficiently absorbs and metabolizes bisphenol A. AB - Skin contact has been hypothesized to contribute to human exposure to bisphenol A (BPA). We examined the diffusion and metabolism of BPA using viable skin models: human skin explants and short-term cultures of pig ear skin, an alternative model for the study of the fate of xenobiotics following contact exposure. 14C-BPA [50 800 nmol] was applied on the surface of skin models. Radioactivity distribution was measured in all skin compartments and in the diffusion cells of static cells diffusion systems. BPA and metabolites were further quantified by radio-HPLC. BPA was efficiently absorbed in short-term cultures, with no major difference between the models used in the study [viable pig ear skin: 65%; viable human explants: 46%; non-viable (previously frozen) pig skin: 58%]. BPA was extensively metabolized in viable systems only. Major BPA metabolites produced by the skin were BPA mono-glucuronide and BPA mono-sulfate, accounting together for 73% and 27% of the dose, in pig and human, respectively. In conclusion, experiments with viable skin models unequivocally demonstrate that BPA is readily absorbed and metabolized by the skin. The trans-dermal route is expected to contribute substantially to BPA exposure in human, when direct contact with BPA (free monomer) occurs. PMID- 21030063 TI - Comments on "Levels of PCDD/F and dioxin-like PCB in Baltic fish of different age and gender" by M. Pandelova, B. Henkelmann, O. Roots, M. Simm, L. Jarv, E. Benfenati and K.-W. Schramm [Chemosphere 71(2) (2008) 369-378]. PMID- 21030064 TI - Exposure patterns of UV filters, fragrances, parabens, phthalates, organochlor pesticides, PBDEs, and PCBs in human milk: correlation of UV filters with use of cosmetics. AB - In order to assess potential risks of exposure to environmental chemicals, more information on concomitant exposure to different chemicals is needed. We present data on chemicals in human milk of a cohort study (2004, 2005, 2006) of 54 mother/child pairs, where for the first time, cosmetic UV filters, synthetic musks, parabens and phthalate metabolites were analyzed in the same sample along with persistent organochlor pollutants (POPs), i.e., organochlor pesticides and metabolites, polybrominated diphenylethers and polychlorinated biphenyls (PCBs). The two groups of chemicals exhibited different exposure patterns. Six out of seven PCB congeners and a majority of pesticides were present in all milk samples, with significant correlations between certain PCB congener and pesticide levels, whereas the cosmetic-derived compounds, UV filters, parabens and synthetic musks, exhibited a more variable exposure pattern with inter-individual differences. UV filters were present in 85.2% of milk samples, in the range of PCB levels. Comparison with a questionnaire revealed a significant correlation between use of products containing UV filters and their presence in milk for two frequently used and detected UV filters, 4-methylbenzylidene camphor and octocrylene, and for the whole group of UV filters. Concentrations of PCBs and organochlor pesticides were within ranges seen in Western and Southern European countries. For several POPs, mean and/or maximum daily intake calculated from individual concentrations was above recent US EPA reference dose values. Our data emphasize the need for analyses of complex mixtures to obtain more information on inter-individual and temporal variability of human exposure to different types of chemicals. PMID- 21030065 TI - Catalytic hydrogenation rate of polycyclic aromatic hydrocarbons in supercritical carbon dioxide containing polymer-stabilized palladium nanoparticles. AB - Catalytic hydrogenation of polycyclic aromatic hydrocarbons (PAHs) with up to four fused benzene rings over high-density-polyethylene-stabilized palladium nanoparticles in supercritical carbon dioxide via in situ UV/Vis spectroscopy is presented. PAHs can be efficiently converted to saturated polycyclic hydrocarbons using this green technique under mild conditions at 20 MPa of CO2 containing 1 MPa of H2 at 40-50 degrees C. Kinetic studies based on in situ UV/Vis spectra of the CO2 phase reveal that the initial hydrogenation of a given PAH and the subsequent hydrogenations of its intermediates are pseudo-first-order. The hydrogenation rate of the latter is always much smaller than that of the former probably due to increasing steric hindrance introduced by the hydrogenated benzene rings of PAHs which impedes the adsorption process and hydrogen access to PAHs on catalyst surfaces. PMID- 21030066 TI - Drug monitoring in systemic lupus erythematosus: a systematic review. AB - OBJECTIVES: To conduct an evidence-based review of the common medication toxicities and strategies and utility of drug toxicity monitoring among patients with systemic lupus erythematosus (SLE). METHODS: PubMed and other databases were searched for articles published between the years 1960 and 2010 for keywords referring to medication toxicity or monitoring strategies for 7 drugs commonly used in SLE. All relevant English-language articles were reviewed. Most of the evidence we reviewed comprised studies that addressed the incidence of toxicity randomized trials that compare different monitoring strategies for these drugs do not exist. RESULTS: Data to describe the frequency of adverse events and appropriate strategies for screening for these events are scarce. Toxicities do not appear to be substantially more common among patients with SLE compared to other conditions for which these drugs are used. CONCLUSIONS: Our review demonstrates that the scientific basis for many aspects of drug toxicity monitoring is weak and that most current recommendations are based largely on expert consensus. We present a future research agenda to address these gaps. PMID- 21030067 TI - Overexpression of transforming growth factor beta1 in malignant prostate cells is partly caused by a runaway of TGF-beta1 auto-induction mediated through a defective recruitment of protein phosphatase 2A by TGF-beta type I receptor. AB - OBJECTIVES: To elucidate the mechanism of transforming growth factor (TGF)-beta1 overexpression in prostate cancer cells. METHODS: Malignant (PC3, DU145) and benign (RWPE1, BPH1) prostate epithelial cells were used. Phosphatase activity was measured using a commercial kit. Recruitment of the regulatory subunit, Balpha, of protein phosphatase 2A (PP2A-Balpha) by TGF-beta type I receptor (TbetaRI) was monitored by coimmunoprecipitation. Blockade of TGF-beta1 signaling in cells was accomplished either by using TGF-beta-neutralizing monoclonal antibody or by transduction of a dominant negative TGF-beta type II receptor retroviral vector. RESULTS: Basal levels of TGF-beta1 in malignant cells were significantly higher than those in benign cells. Blockade of TGF-beta signaling resulted in a significant decrease in TGF-beta1 expression in malignant cells, but not in benign cells. Upon TGF-beta1 treatment (10 ng/mL), TGF-beta1 expression was increased in malignant cells, but not in benign cells. This differential TGF-beta1 auto-induction between benign and malignant cells correlated with differential activation of extracellular signal-regulated kinase (ERK). Following TGF-beta1 treatment, the activity of serine/threonine phosphatase and recruitment of PP2A-Balpha by TbetaRI increased in benign cells, but not in malignant cells. Inhibition of PP2A in benign cells resulted in an increase in ERK activation and in TGF-beta1 auto-induction after TGF-beta1 (10 ng/mL) treatment. CONCLUSIONS: These results suggest that TGF-beta1 overexpression in malignant cells is caused, at least in part, by a runaway of TGF-beta1 auto-induction through ERK activation because of a defective recruitment of PP2A-Balpha by TbetaRI. PMID- 21030068 TI - Everything you always wanted to know about evaluating prediction models (but were too afraid to ask). PMID- 21030069 TI - Heating up or cooling up the brain? MEG evidence that phrasal verbs are lexical units. AB - There is a considerable linguistic debate on whether phrasal verbs (e.g., turn up, break down) are processed as two separate words connected by a syntactic rule or whether they form a single lexical unit. Moreover, views differ on whether meaning (transparency vs. opacity) plays a role in determining their syntactically-connected or lexical status. As linguistic arguments could not settle these issues, we used neurophysiological brain imaging to address them. Applying a multi-feature Mismatch Negativity (MMN) design with subjects instructed to ignore speech stimuli, we recorded magnetic brain responses to particles (up, down) auditorily presented as infrequent "deviant" stimuli in the context of frequently occurring verb "standard" stimuli. Already at latencies below 200ms, magnetic brain responses were larger to particles appearing in existing phrasal verbs (e.g. rise up) than to particles appearing in non-existing combinations (e.g. *fall up), regardless of whether particles carried a literal or metaphorical sense (e.g. rise up, heat up). Previous research found an enhanced MMN response to morphemes in existing (as opposed to non-existing) words but a reduced MMN to words in grammatically acceptable (as opposed to unacceptable) combinations. The increased brain activation to particles in real phrasal verbs reported here is consistent with the lexical enhancement but inconsistent with the syntactic reduction of the MMN, thus providing neurophysiological support that a congruent verb-particle sequence is not assembled syntactically but rather accessed as a single lexical chunk. PMID- 21030070 TI - Paediatric mortality related to H1N1 infection in England. PMID- 21030071 TI - Paediatric mortality related to pandemic influenza A H1N1 infection in England: an observational population-based study. AB - BACKGROUND: Young people (aged 0-18 years) have been disproportionately affected by pandemic influenza A H1N1 infection. We aimed to analyse paediatric mortality to inform clinical and public health policies for future influenza seasons and pandemics. METHODS: All paediatric deaths related to pandemic influenza A H1N1 infection from June 26, 2009, to March 22, 2010 in England were identified through daily reporting systems and cross-checking of records and were validated by confirmation of influenza infection by laboratory results or death certificates. Clinicians responsible for each individual child provided detailed information about past medical history, presentation, and clinical course of the acute illness. Case estimates of influenza A H1N1 were obtained from the Health Protection Agency. The primary outcome measures were population mortality rates and case-fatality rates. FINDINGS: 70 paediatric deaths related to pandemic influenza A H1N1 were reported. Childhood mortality rate was 6 per million population. The rate was highest for children aged less than 1 year. Mortality rates were higher for Bangladeshi children (47 deaths per million population [95% CI 17-103]) and Pakistani children (36 deaths per million population [18-64]) than for white British children (4 deaths per million [3-6]). 15 (21%) children who died were previously healthy; 45 (64%) had severe pre-existing disorders. The highest age-standardised mortality rate for a pre-existing disorder was for chronic neurological disease (1536 per million population). 19 (27%) deaths occurred before inpatient admission. Children in this subgroup were significantly more likely to have been healthy or had only mild pre-existing disorders than those who died after admission (p=0.0109). Overall, 45 (64%) children had received oseltamivir: seven within 48 h of symptom onset. INTERPRETATION: Vaccination priority should be for children at increased risk of severe illness or death from influenza. This group might include those with specified pre existing disorders and those in some ethnic minority groups. Early pre-hospital supportive and therapeutic care is also important. FUNDING: Department of Health, UK. PMID- 21030072 TI - Robust cell integration from co-transplantation of biodegradable MMP2-PLGA microspheres with retinal progenitor cells. AB - The failure of the adult mammalian retina to regenerate can be partly attributed to the barrier formed by inhibitory extracellular matrix (ECM) and cell adhesion molecules, such as CD44 and neurocan, after degeneration. These molecules act to separate a sub-retinal graft from integrating into the host retina. It has been shown that matrix metalloproteinase 2 (MMP2) can promote host-donor integration by degrading these molecules. In order to enhance cellular integration and promote retinal repopulation, we co-transplanted biodegradable poly(lactic-co glycolic acid) (PLGA) microspheres that have the ability to deliver active MMP2 with retinal progenitor cells (RPCs) to the sub-retinal space of adult retinal degenerative Rho-/- mice. Following delivery, significant degradation of CD44 and neurocan at the outer surface of the degenerative retina without disruption of the host retinal architecture was observed. Coincident with this, we observed a significant increase in the number of cells migrating beyond the barrier into the degenerative retina. No changes in the differentiation characteristics of RPCs were observed. Cells in the outer nuclear layer (ONL) could express the mature photoreceptor markers recoverin, make contacts with residual protein kinase C (PKC)-positive cells and express the ribbon synapse protein bassoon. Thus, co transplantation of MMP2-PLGA microspheres with RPCs provides controlled release of active MMP2 to the site of retinal degeneration, stimulating inhibitory barrier removal and enhancing cell integration. This suggests a practical and effective strategy for retinal repair. PMID- 21030073 TI - The effectiveness of a magnetic nanoparticle-based delivery system for BCNU in the treatment of gliomas. AB - This study describes the creation and characterization of drug carriers prepared using the polymer poly[aniline-co-N-(1-one-butyric acid) aniline] (SPAnH) coated on Fe(3)O(4) cores to form three types of magnetic nanoparticles (MNPs); these particles were used to enhance the therapeutic capacity and improve the thermal stability of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), a compound used to treat brain tumors. The average hydrodynamic diameter of the MNPs was 89.2 +/- 8.5 nm and all the MNPs displayed superparamagnetic properties. A maximum effective dose of 379.34 MUg BCNU could be immobilized on 1 mg of MNP-3 (bound BCNU-3). Bound-BCNU-3 was more stable than free-BCNU when stored at 4 degrees C, 25 degrees C or 37 degrees C. Bound-BCNU-3 could be concentrated at targeted sites in vitro and in vivo using an externally applied magnet. When applied to brain tumors, magnetic targeting increased the concentration and retention of bound-BCNU-3. This drug delivery system promises to provide more effective tumor treatment using lower therapeutic doses and potentially reducing the side effects of chemotherapy. PMID- 21030074 TI - Pyridylhydrazone-based PEGylation for pH-reversible lipopolyplex shielding. AB - PEGylation, which is reversed after the therapeutic agent reaches the target cell, presents an attractive feature for drug, protein or nucleic acid delivery. For bioreversible surface shielding of DNA lipopolyplexes, the bifunctional, endosomal pH-cleavable reagent OPSS-PEG-HZN-Chol [omega-2-pyridyldithio poly (ethylene) glycol alpha-(butyraldehyde) (N(1)-cholesteryloxycarbonyl-1, 2 diaminoethane amidocarboxy) pyridyl hydrazone] was synthesized. Both OPSS-PEG-HZN Chol and its corresponding pH stable analog OPSS-PEG-Chol form micelles which remain stable and shielded at pH 7.4 and 37 degrees C as demonstrated by size exclusion chromatography. At endosomal pH 5.4, OPSS-PEG-HZN-Chol micelles are destroyed within 30 min at 37 degrees C, while OPSS-PEG-Chol micelles remain stable. Lipopolyplexes composed of DNA condensed with polyethylenimine (PEI), phospholipids including dioleoyl phosphatidylethanolamine (DOPE) and pH-labile OPSS-PEG-HZN-Chol were prepared by the ethanol injection technique. The optimal formulation yielded particles of 160 nm size and a zeta potential of +7 mV. At physiological neutral conditions pyridylhydrazone-based PEGylated lipopolyplexes were as stable as standard PEGylated lipopolyplexes. At pH 5.4, an increase in size was observed only for pH-reversible HZN lipopolyplexes. Transfection with plasmids encoding for luciferase or EGFP resulted in an upto 40-fold enhancement in gene expression with the reversibly PEGylated lipopolyplexes compared to the stably PEGylated ones. Incorporation of a synthetic peptidic ligand for transferrin receptor targeting further improved transfection efficiency in transferrin overexpressing tumor cells. Cellular association and uptake studies by flow cytometry and confocal laser scanning microscopy with an Alexa-labeled PEG shield revealed intracellular deshielding in case of the HZN lipopolyplexes. PMID- 21030075 TI - The role of integrins in the recognition and response of dendritic cells to biomaterials. AB - Biomaterials have the potential to be utilized as immunostimulatory or immunosuppressive delivery agents for biologics. It is hypothesized that this is directed by the ability of a biomaterial to drive dendritic cells (DC) in situ toward an immunostimulatory or an immunosuppressive phenotype, respectively. However, the specific pattern recognition receptors (PRRs) that DCs use to recognize and respond to biomaterials are unknown. From among the many receptors that DCs use to recognize and respond to foreign entities, herein the focus is on integrins. A biomaterial that induces DC maturation, namely poly(lactic-co glycolic) acid (PLGA), supported increased human monocyte-derived DC adhesion and up-regulation of integrin receptor gene expression, measured via RT-PCR, as compared to culture on tissue culture polystyrene (TCPS). This was not observed for a biomaterial that does not support DC maturation. Through antibody-blocking techniques, the adhesion to both TCPS and PLGA was found to be beta(2) integrin dependent and beta(1) independent. Significantly, inhibiting beta(2)-mediated adhesion to biomaterials via blocking antibodies also lowered the level of maturation of DCs (CD86 expression). beta(2) integrins (but not beta(1)) were found localized in biomaterial-adherent DC podosomes and also were found in direct contact with the PLGA surface. Therefore, it appeared that beta(2) integrin-mediated adhesion is involved in determining the state of DC maturation on the PLGA surface. DC adhesion to biomaterials may be engaged or avoided to manipulate an immune response to biological component delivered with a biomaterial carrier. PMID- 21030076 TI - Differential affinity of vitronectin versus collagen for synthetic biodegradable scaffolds for urethroplastic applications. AB - Cell-seeded synthetic polymer scaffolds constitute an emerging technology for urethroplastic applications. The study goal was to identify urethral proteins appropriate for cell attachment and optimize their adsorption onto two types of scaffolds: porous poly(ester urethane) with a poly(caprolactone) soft segment (PEU-PCL) and poly-(96% L/4% D)-lactic acid (P96L/4DLA). Specimens from eight men undergoing urethral reconstruction for stricture diseases were subjected to immunohistochemical analysis. Type I collagen, type IV collagen and vitronectin were detected at the interface between the epithelium and its basement membrane. Electrophoresis confirmed that polypeptide chains in the starting material were also present in fractions eluted from adsorbed scaffolds. Over a 4 week incubation assay, only vitronectin exhibited 100% retention levels for all scaffolds. The saturation point for each protein on each scaffold type was determined by titration and ELISA. The collective evidence indicates the concept that vitronectin > type IV collagen > type I collagen are preferred adsorption proteins for PEU-PCL and P96L/4DLA. PMID- 21030077 TI - Obesity and the placenta: A consideration of nutrient exchange mechanisms in relation to aberrant fetal growth. AB - The obesity epidemic, including childhood obesity, is rapidly gaining strength as one of the most significant challenges to the health of the global community in the 21st Century. The proportion of women who are obese at the beginning of pregnancy is also increasing. These women and their babies are at high risk of pregnancy complications, and of programming for metabolic disease in adult life. In particular, maternal obesity is associated with aberrant fetal growth, encompassing both growth restricted and large for gestational age, or macrosomic fetuses. This article considers the potential effect of obesity and adipose tissue on placental nutrient exchange mechanisms in relation to aberrant fetal growth. The review emphasizes the dearth of work on this topic to date despite its importance to current and future healthcare of the population. PMID- 21030078 TI - Relationship between deoxycytidine kinase (DCK) genotypic variants and fludarabine toxicity in patients with follicular lymphoma. AB - DCK catalyzes the intracellular phosphorylation of fludarabine. The promoter and coding region of the DCK gene were analyzed in 74 follicular lymphoma (FL) patients receiving a therapeutic regimen that included fludarabine. DCK mRNA expression was quantified in a cohort of healthy donors. Four previously described genotypic variants, -360C>G, -201C>T (rs2306744), C28624T (rs11544786) and c.91+37G>C (rs9997790), as well as the new variant, -12C>G, were identified. Variant C28624T showed a lower risk of lymphopenia (P=0.04), but a higher risk of neutropenia (P=0.04). Statistical significance was found in bivariate logistic regression between lymphopenia and infectious episodes in the induction period (odds ratio 3.85, P=0.04). PMID- 21030079 TI - A prospective evaluation of cardiac function in patients with chronic myeloid leukaemia treated with imatinib. AB - In vitro studies have suggested that imatinib may be toxic to cardiac myocytes. Though retrospective studies have not shown clinical heart failure, these did not look for subtle cardiac damage. We have carried out a prospective cardiac assessment in 59 chronic myeloid leukaemia (CML) patients treated with imatinib for a median of 3.4 years, using echocardiography and MUGA scanning, with the latter repeated after a further year. We report no evidence of myocardial deterioration, either at baseline or over 12 months of imatinib treatment. Imatinib cardiotoxicity is not an important clinical consideration for CML patients or their advisors. PMID- 21030080 TI - Child homicide on the territory of Belgrade. AB - OBJECTIVE: This study examines the incidence and other epidemiological and medico legal characteristics of child homicide in the territory of Belgrade, Republic of Serbia. METHODS: We performed a retrospective analysis of all autopsies carried out at the Institute of Forensic Medicine in Belgrade during a 15 year period between 1991 and 2005, focusing on homicide cases of victims aged 0-14 years. These were then analyzed in terms of number of deaths, mortality rates, age, and sex of the victim, relation to the perpetrator, and cause of death and injury. RESULTS: Forty-six homicides were identified where the victims were aged 0-14 years. These included 24 girls and 22 boys. In 32 cases (69.6%) the perpetrator was one of the child's birth parents, more frequently the mother. Blunt head trauma was the most frequent cause of death, followed by exsanguination. In 9 cases (19.5%) there was evidence of physical abuse; 16 children died in the setting of multiple homicide and/or murder/suicide. In 4 cases (8.7%) there was evidence of neglect which contributed to the fatal outcome. There were 10 cases of neonaticide within the 46 homicides. There were, however, 49 further cases where bodies of newborn infants were discovered after having been disposed of in suspicious circumstances. CONCLUSIONS: Proportionally, the largest number of victims fell within the 1-4 years age group, with a slight preponderance of females, most of them killed at home by a close family member, usually the mother. Blunt head trauma was the single most frequent cause of death. Injury patterns consistent with child abuse were identified among 20% of the study group. PMID- 21030082 TI - The inclusion of disability as a condition for termination of parental rights. AB - OBJECTIVES: All 50 states and the District of Columbia have statutes outlining the grounds for terminating parental rights (TPR) in relation to child abuse and neglect. Although recent research has found that parents with disabilities are not more likely to maltreat their children than parents without disabilities (Glaun & Brown, 1999; Oyserman, Mowbray, Meares, & Firminger, 2000), studies have found very high rates of TPR of parents with disabilities (Accardo & Whitman, 1989). The objective of this study is to examine how states are including disability in their TPR statutes. METHODS: This study used legal document analysis, consisting of a comprehensive Boolean search of the state codes of the 50 states and District of Columbia (DC) relating to TPR, using the most recent state code available on Lexis-Nexis in August 2005. TPR and related statutes were searched for contemporary and historical disability related terms and their common cognates, such as: "mental," "disability," "handicap," and "incapacity." Two researchers independently conducted the searches, and the searches were reconciled. A code list was then developed to measure for inclusion of disability, preciseness, scope, use of language, and references to accessibility or fairness. Statutes were then reanalyzed, and groupings developed. RESULTS: Thirty-seven states included disability-related grounds for termination of parental rights, while 14 states did not include disability language as grounds for termination. Many of these state codes used outdated terminology, imprecise definitions, and emphasized disability status rather than behavior. All of the 14 states that do not include disability in TPR grounds allowed for termination based on neglectful parental behavior that may be influenced by a disability. CONCLUSIONS: The use of disability language in TPR statutes can put an undue focus on the condition of having a disability, rather than parenting behavior. IMPLICATIONS: This paper recommends that states consider removing disability language from their statutes, as such language risks taking the emphasis away from the assessment based on parenting behavior. PMID- 21030081 TI - Trajectories of maternal harsh parenting in the first 3 years of life. AB - OBJECTIVE: Despite the high prevalence rates of harsh parenting, the nature of developmental change in this domain early in life and the factors that contribute to changes in harsh parenting over time are not well understood. The present study examined developmental patterns in maternal harsh parenting behavior from birth to age 3 years and their related longitudinal risk factors (contextual and intrapersonal). Partner aggression was also tested as a time-varying predictor to examine its time-specific influence on maternal harsh parenting. METHODS: Longitudinal data from 4 assessments of a community sample of 488 at-risk mothers were analyzed using latent growth curve modeling. Maternal risk factors and harsh parenting behaviors were assessed at birth and at ages 1, 2, and 3 years. RESULTS: There was a significant increase in maternal harsh parenting from birth to age 3, particularly between ages 1 and 2. There was a significant direct effect of maternal alcohol use and abuse history on maternal harsh parenting at age 3, and maternal age was positively associated with change in maternal harsh parenting over time. In addition, partner aggression was significantly and positively associated with maternal harsh parenting at each time point. CONCLUSIONS: The findings suggest possible developmental trends in the emergence of maternal harsh parenting during infancy and toddlerhood. Further investigation is needed to elucidate individual differences in the developmental patterns and to differentiate predictive factors that persist across time and factors that are unique to specific developmental stages. PRACTICE IMPLICATIONS: The overall high prevalence rates of harsh parenting behavior and growth of such behavior in infancy and toddlerhood support the need for developmentally sensitive early intervention programs. PMID- 21030083 TI - The presence of a stepfather and child physical abuse, as reported by a sample of Brazilian mothers in Rio de Janeiro. AB - OBJECTIVE: Substitute fathers are often reported to commit child abuse at higher rates than birth (i.e., putative genetic) fathers. Due to the paucity of studies, especially in developing countries, and to some conflicting results from developed countries regarding the identity of perpetrators of less extreme forms of physical abuse of children in stepfamilies, the aim of this study was to assess whether the presence of a stepfather would constitute a risk factor for violence against Brazilian children, as reported by their mothers. METHODS: Three hundred eighty five women with a current male partner and a child aged 1-12 years were interviewed. Child physical abuse was assessed using the Conflict Tactic Scales Parent Child. Data were analyzed through multiple logistic regressions. RESULTS: Physical abuse (including severe physical abuse) was reported for 34.0% of the children with stepfathers (N=54) versus 17.6% of those living with putative genetic fathers (N=331). When adjusted for income, education, ages, whether the child was the first born, number of siblings, number of people in the household, how much time the man spent with the child, how many years he resided with the mother, and alcohol abuse and drug use by the mother and her partner, the adjusted odds ratio was 2.7 (95% CI: 1.2-5.9) for stepfather households over 2 genetic parent households. Surprisingly, the elevated risk to stepchildren was due to alleged abuse by the interviewee herself rather than her partner. CONCLUSION: Brazilian mothers professed to abuse their own children at substantially higher rates when their male partners were stepfathers to the focal child as compared to genetic fathers. PMID- 21030084 TI - Emotion dysregulation and risky sexual behavior in revictimization. AB - OBJECTIVE: The current study examined emotion dysregulation as a mechanism underlying risky sexual behavior and sexual revictimization among adult victims of child sexual abuse (CSA) and child physical abuse (CPA). METHODS: Participants were 752 college women. Victimization history, emotion dysregulation, and risky sexual behavior were assessed with anonymous, self-report surveys utilizing a cross-sectional design. RESULTS: Approximately 6.3% of participants reported CSA, 25.5% reported CPA, and 17.8% reported rape during adolescence or adulthood. CSA and CPA were associated with increased risk for adolescent/adult rape; 29.8% of CSA victims and 24.3% of CPA victims were revictimized. Path analytic models tested hypothesized relationships among child abuse, emotion dysregulation, adolescent/adult rape and three forms of risky sexual behavior (e.g., failure to use condoms, contraception, or having sex with someone under the influence of alcohol/drugs), including frequency of risky sexual behavior with a regular dating partner, with a stranger, and lifetime number of intercourse partners. Emotion dysregulation mediated revictimization for both CSA and CPA. Emotion dysregulation also predicted lifetime number of sexual partners and frequency of risky sex with a stranger, but not frequency of risky sex with a regular dating partner. CONCLUSIONS: Findings suggest that emotion dysregulation is a distal predictor, and risky sex, particularly with lesser known partners, is a proximal predictor of sexual revictimization. Because emotion dysregulation also maintained a significant direct path to revictimization, risky sexual behavior appears to be one of several proximal risk factors for revictimization. PRACTICE IMPLICATIONS: Findings confirm that emotion dysregulation is a critical pathway to more proximal risk factors such as risky sexual behavior, and suggest that clinical interventions aimed at improving emotion dysregulation may help reduce risky sexual behavior and risk for revictimization. PMID- 21030085 TI - Allelopatic effects of cyanobacteria extracts containing microcystins on Medicago sativa-Rhizobia symbiosis. AB - The eutrophication of water leads to massive blooms of cyanobacteria potentially producers of highly toxic substances: cyanotoxins, especially microcystins (MC). The contamination of water used for irrigation by these toxins, can cause several adverse effects on plants and microorganisms. In this work, we report the phytotoxic effects of microcystins on the development of symbiosis between the leguminous plant Medicago sativa (Alfalfa) and rhizobia strains. The exposure of rhizobial strains to three different concentrations 0.01, 0.05 and 0.1 MUg MC ml( 1) led to decrease on the bacteria growth. The strains of rhizobia Rh L1, Rh L2, Rh L3 and Rh L4 reduced their growth to, respectively, 20.85%, 20.80%, 33.19% and 25.65%. The chronic exposure of alfalfa seeds and seedlings to different MC concentrations affects the whole stages of plant development. The germination process has also been disrupted with an inhibition, which reaches 68.34% for a 22.24 MUg MC ml(-1). Further, seedlings growth and photosynthetic process were also disrupted. The toxins reduced significantly the roots length and nodule formation and leads to an oxidative stress. Thus, the MCs contained in lake water and used for irrigation affect the development of symbiosis between M. sativa and Rhizobia. PMID- 21030086 TI - Growth and metal accumulation in Porcellio scaber exposed to poplar litter from Cd-, Pb-, and Zn-contaminated sites. AB - This study aimed at determining, in the laboratory, the effects of poplar litter collected in woody habitats contaminated by heavy metals on growth and metal accumulation in the terrestrial isopod Porcellio scaber. Cd, Pb, and Zn pseudototal and CaCl(2)-extractable concentrations in litter types were determined using AAS. Juveniles were fed ad libitum, individually, for 28 days with four litter types presenting an increasing gradient of metal contamination. Individuals were weighed every week and metal body burdens were determined at the end of the experiment. From the first week until the end of the experiment, a decrease in P. scaber growth related to the increase of metal concentration in litter types was recorded. Significant correlations were observed between metal body burdens and metal concentrations in litter types. However, Cd accumulation in woodlice appeared to be related to the Cd/Zn concentration ratio in litter types. All these results showed the potential of weight gain in P. scaber as a suitable indicator for litter quality assessment with ecological relevance. PMID- 21030087 TI - Long-term effects of propolis on serum biochemical parameters of rainbow trout (Oncorhynchus mykiss). AB - Long-term effects of propolis administration on serum biochemical parameters of rainbow trout (Oncorhynchus mykiss) were investigated. To determine the possible toxicity and side effects of propolis, fish were fed on diets containing 0, 0.5, 1.5, 4.5 and 9 g propolis/kg diet for 8 weeks. At the end of the experiment, various seric biochemical parameters were determined. Our results showed that all dosages induced no significant alterations in growth parameters and the seric levels of total protein, albumin, globulin, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides and activities of glutamic pyruvic transaminase, glutamic oxaloacetic transaminase, alkaline phosphatase and lactate dehydrogenase, when compared to the control group. On the basis of our findings, propolis is a non-toxic substance for rainbow trout and its long-term administration might not have any side effects. PMID- 21030088 TI - Influences of soil properties and leaching on nickel toxicity to barley root elongation. AB - The influence of soil properties on Ni toxicity to barley root elongation was investigated using 17 Chinese soils treated with soluble Ni salts, with and without leaching. The effective concentration of added Ni causing 50% inhibition (EC50) in barley root elongation ranged from 48 to 2519 mg/kg in unleached soils and 46 to >2381 mg/kg in leached soils. Leaching decreased Ni phytotoxicity significantly for approximately 90% of soils, and the effect was most pronounced for soils with pH >=8.2. Soil pH was the most important factor controlling Ni toxicity in soils, explaining approximately 68% of the variance in unleached and leached EC50 values. Regression models between toxicity thresholds and soil pH, soil organic carbon content, or effective cation exchange capacity were developed. The models showed good agreement with those developed previously for European soils (r(2)=0.87). These quantitative relationships between Ni toxicity and soil properties are helpful to develop soil-specific guidance on Ni toxicity thresholds for China. PMID- 21030089 TI - Guardianship for your own good: Improving the well-being of respondents and wards in the USA. AB - Adult guardianship is a coercive exercise of the state's power over an innocent individual, justified only by: 1) the ward's incapacity; and 2) the need to protect the ward's well-being. The raison d'etre of guardianship is to improve the well-being of the incapacitated ward. Studies of actual guardianship proceedings have long indicated serious ongoing concerns with the process. Repeated revisions of statutes have attempted to improve guardianship procedures, with some success. However, relatively little attention has been paid to the actual effect of guardianship on the well-being of respondents and wards, when the system functions as intended. The presumption that guardianship, when not abused, is in the best interests of an incapacitated adult is called into serious question by empirical research into the role of internal locus of control and autonomy on human well-being. Indeed, a wide range of data indicates that guardianship itself can have significant negative effects on the physical and mental well-being of respondents and wards. The guardianship system must be reformed to maximize the therapeutic effects of guardianship and to minimize the unnecessarily anti-therapeutic effects. I examine the effects of guardianship from a therapeutic jurisprudence perspective and propose and analyze modifications that could enhance the therapeutic effects of guardianship. PMID- 21030090 TI - Association of seropositivity for influenza and coronaviruses with history of mood disorders and suicide attempts. AB - BACKGROUND: Anecdotal reports of mood disorder following infection with common respiratory viruses with neurotropic potential have been in existence since the last century. Nevertheless, systematic studies on the association between these viruses and mood disorders are lacking. METHODS: Influenza A, B and coronavirus antibody titers were measured in 257 subjects with recurrent unipolar and bipolar disorder and healthy controls, by SCID. Pearson's chi2 tests and logistic regression models were used to analyze associations between seropositivity for coronaviruses, influenza A and B viruses and the following: a) history of recurrent mood disorders b) having attempted suicide in the past c) uni- vs. bi polarity and d) presence of psychotic symptoms during mood episodes. RESULTS: Seropositivity for influenza A (p=0.004), B (p<0.0001) and coronaviruses (p<0.0001) were associated with history of mood disorders but not with the specific diagnosis of unipolar or bipolar depression. Seropositivity for influenza B was significantly associated with a history of suicide attempt (p=0.001) and history of psychotic symptoms (p=0.005). LIMITATIONS: The design was cross-sectional. Socioeconomic factors, inflammatory markers, and axis II psychopathology were not assessed. CONCLUSIONS: The association of seropositivity for influenza and coronaviruses with a history of mood disorders, and influenza B with suicidal behavior require replication in larger longitudinal samples. The need for these studies is additionally supported by the high incidence of these viral infections, the high prevalence of mood disorders, and resilience of suicide epidemics. PMID- 21030091 TI - An item response analysis of the DSM-IV criteria for major depression: findings from the Australian National Survey of Mental Health and Wellbeing. AB - BACKGROUND: This study examines the psychometric properties and presence of gender bias in the major depression criteria using data from the Australian general population. METHODS: Data came from a subsample of respondents from the 1997 National Survey of Mental Health and Wellbeing (NSMHWB; n=2061). A two parameter logistic model was employed to yield severity and discrimination parameters, and the IRT log-likelihood-ratio test for differential item functioning (IRTLRDIF) procedure was utilized to evaluate gender bias. RESULTS: DIF analyses indicated that the psychomotor difficulties criterion was endorsed at lower levels of severity by males than females. In general, the criteria were arrayed along a continuum of depression severity. Discrimination was greatest for concentration difficulties/indecision and lowest for death/suicidal thoughts and worthlessness/guilt. Worthlessness/guilt, psychomotor difficulties, and death/suicidal thoughts tapped the severe end of the depression continuum, whereas concentration difficulties/indecision and sleep disturbance tapped the mild range. LIMITATIONS: The inclusion of stem questions precluded examination of two core symptoms of depression (depressed mood and loss of interest). CONCLUSIONS: Collectively, the criteria performed well in defining a latent continuum of major depression. Few gender differences were observed, with the exception of the psychomotor difficulties criterion. Quantitative and qualitative analyses collectively hold promise of providing a scientifically rigorous basis for empirically-based modifications to the psychiatric classification system. PMID- 21030092 TI - Brain effects of antidepressants in major depression: a meta-analysis of emotional processing studies. AB - BACKGROUND: A consistent brain activity pattern has been identified in major depression across many resting positron emission tomography (PET) studies. This dysfunctional pattern seems to be normalized by antidepressant treatment. The aim of this meta-analysis was to identify more clearly the pattern associated with clinical improvement of depression following an antidepressant drug treatment, in emotional activation studies using functional magnetic resonance imaging (fMRI). METHODS: A quantitative Activation Likelihood Estimation (ALE) meta-analysis was performed across 9 emotional activation fMRI and PET studies (126 patients) using the Activation Likelihood Estimation technique. RESULTS: Following the antidepressant drug treatment, the activation of dorsolateral, dorsomedial and ventrolateral prefrontal cortices was increased whereas the activation of the amygdala, hippocampus, parahippocampal region, ventral anterior cingulate cortex, orbitofrontal cortex, and insula was decreased. Additionally, there was a decreased activation in the anterior (BA 32) and posterior cingulate cortices, as well as in the precuneus and inferior parietal lobule, which could reflect a restored deactivation of the default mode network. LIMITATIONS: The small number of emotional activation studies, using heterogeneous tasks, included in the ALE analysis. CONCLUSIONS: The activation of several brain regions involved in major depression, in response to emotional stimuli, was normalized after antidepressant treatment. To refine our knowledge of antidepressants' effect on the neural bases of emotional processing in major depression, neuroimaging studies should use consistent emotional tasks related to depressive symptoms and that involve the default mode network, such as self-referential processing tasks. PMID- 21030093 TI - Coding region polymorphisms in the indoleamine 2,3-dioxygenase (INDO) gene and recurrent spontaneous abortion. AB - Indoleamine 2,3-dioxygenase (INDO) catalyzes degradation of the indole ring of indoleamines and locally depletes tryptophan. INDO expression suppresses T cell proliferation and activation. Genetic variation in the INDO gene may contribute to the variable INDO enzyme expression, activity and severity of some diseases. Recurrent spontaneous abortion (RSA) is a common pregnancy complication and the exact causes of RSA are not yet known. We performed an association study between INDO single nucleotide polymorphisms (SNPs) and RSA. To identify INDO SNPs we sequenced DNA samples for ten exons and adjacent intronic regions from 111 RSA patients. Consequently 10 SNPs were detected; four in exons (one in exon 4, two in exon 9 and one in exon 10) and six in intronic regions (one in intron 3, three in intron 6, one in intron 8 and one in intron 9). Three (IVS3+562 del C, IVS8+116 T->G and IVS9+2431 G->A) of these ten SNPs have been registered at the NCBI SNP database. Statistical analysis of allele, genotype and haplotype frequency distribution in the three most frequent SNPs (IVS3+562 del C, IVS6+61 G >A and IVS9+2431 G->A) showed no significant differences between the 111 RSA and 105 matched control women. CGA and CGG were the most frequent haplotypes in both the RSA and control groups. We conclude that there is no association between INDO polymorphisms and susceptibility of Iranian women to RSA. PMID- 21030094 TI - Treatment outcomes of juvenile nasopharyngeal angiofibroma according to surgical approach. AB - OBJECTIVE: This is a retrospective study to assess treatment outcomes according to stage and surgical approach in advanced juvenile nasopharyngeal angiofibroma (JNA). METHODS: We retrospectively evaluated 20 JNA patients diagnosed and treated at our hospital. We only enrolled advanced disease with Radkowski stages greater than I and with minimum follow-up of 1 year (range 1-8.5). RESULTS: Recurrence or remnants were observed in 7 patients out of 20 patients (35.0%) who underwent primary surgical resection of advanced JNA and the mean interval to recurrence was 15.6 months (range 6-38). A recurrence rate according to a different stage was as follows: 33.3% in stage IIa, 33.3% in stage IIb, 50.0% in stage IIc and no recurrence in stage III. An endoscopic approach was chosen in 4 patients among these patients, four were classified as stage IIb tumors, one as a stage IIc tumor, with a recurrence rate of 25.0%, but no recurrence found in stage IIa disease. A midfacial degloving approach was used in 7 patients, with a recurrence rate of 42.9% and maxillary swing approach was taken in 3 patients with complete control. Postoperative complications required interventions occurred in 14.8%, more in the invasive maxillary swing or infratemporal fossa approaches. CONCLUSIONS: Although selecting minimal invasive or invasive approaches is equivocal, we recommend using the endoscopic approach or a midfacial degloving approach for the treatment of JNA extended to the pterygopalatine fossa. For stage III, aggressive surgery is preferable to guaranty a complete resection even if postoperative complications are more frequent. For a stage IIc, we could choose between a minimally invasive approach or a more aggressive one balancing between the possibility of salvage surgery in the future and the occurrence of postoperative healing problems. PMID- 21030096 TI - HLA-B27-associated J-wave--a new variant of HLA-B27-associated cardiac disease? PMID- 21030097 TI - Association between risk-assessment scores and individual-cow Johne's disease test status over time on seven Michigan, USA dairy herds. AB - To evaluate the effectiveness of management practices implemented to control the spread of Johne's disease (JD), we conducted a 5-year observational study (January 2003 to December 2007) on seven Michigan, USA dairy herds containing cows infected with Mycobacterium avium subsp. paratuberculosis (MAP; the causative agent of the disease). The JD incidence and prevalence was monitored in each herd annually by serum ELISA and/or fecal culture of all adult cows. A JDCP was designed specifically for each herd based on the results of an initial risk assessment. The risk-assessment was repeated annually and the control program updated as needed. Herd risk-assessment scores were used to measure compliance with the control program and create JD-risk profiles for individual cows raised on the farms. The association between specific risk-assessment scores and the JD test status of individual cows was evaluated using logistic regression. We accounted for clustering of cows within herds using generalized estimating equations (GEE). Multivariable models were built with purposeful selection of risk factors assessed on univariable analyses. The dataset analyzed consisted of 3707 cows raised on the respective farms, of which 616 were classified as infected with MAP based on testing positive on fecal culture or serum ELISA. Of the cows that were not exposed to the control program, 20% were classified as infected, while only 7% of cows that were exposed to the control program were infected. The final multivariable model consisted of two factors: exposure to adult cows other than dam at birth (OR=1.09, 95% CI: 1.06, 1.13), and feeding colostrum from one cow to multiple calves (OR=1.10, 95% CI: 1.09, 1.12). Based on this study, implementing practices that minimize the exposure of newborn calves to MAP being shed by infected adult cows should take priority. PMID- 21030098 TI - Making the most of 'omics' for crop breeding. AB - Adoption of new breeding technologies is likely to underpin future gains in crop productivity. The rapid advances in 'omics' technologies provide an opportunity to generate new datasets for crop species. Integration of genome and functional omics data with genetic and phenotypic information is leading to the identification of genes and pathways responsible for important agronomic phenotypes. In addition, high-throughput genotyping technologies enable the screening of large germplasm collections to identify novel alleles from diverse sources, thus offering a major expansion in the variation available for breeding. In this review, we discuss these advances, which have opened the door to new techniques for construction and screening of breeding populations, to increase ultimately the efficiency of selection and accelerate the rates of genetic gain. PMID- 21030095 TI - Activation of cortical interneurons during sleep: an anatomical link to homeostatic sleep regulation? AB - Although slow wave activity in the EEG has been linked to homeostatic sleep regulation, the neurobiological substrate of sleep homeostasis is not well understood. Whereas cortical neurons typically exhibit reduced discharge rates during slow wave sleep (SWS), a subpopulation of GABAergic interneurons, which express the enzyme neuronal nitric oxide synthase (nNOS), has recently been found to be activated during SWS. The extent of activation of these nNOS neurons is proportional to homeostatic sleep 'drive'. These cells are an exception among cortical interneurons in that they are projection neurons. We propose that cortical nNOS neurons are positioned to influence neuronal activity across widespread brain areas. They could thus provide a long-sought anatomical link for understanding homeostatic sleep regulation. PMID- 21030099 TI - Basketball training increases striatum volume. AB - The striatum is associated with the learning and retention of motor skills. Several studies have shown that motor learning induces neuronal changes in the striatum. We investigated whether macroscopic change in striatum volume occurs in a segment of the human population who learned basketball-related motor skills and practiced them throughout their entire athletic life. Three-dimensional magnetic resonance imaging volumetry was performed in basketball players and healthy controls, and striatum volumes were compared based on basketball proficiency, region and side. We identified morphological enlargement in the striatum of basketball players in comparison with controls. Our results suggest that continued practice and repetitive performance of basketball-related motor skills may induce plastic structural changes in the human striatum. PMID- 21030100 TI - Oral health content in diabetes self-management education programs. AB - Oral health information was included in 89.5% of diabetes education programs in states with high diabetes prevalence compared to 85.9% in low prevalence states (P = 0.22). Comparing the high to low diabetes prevalence states, there were significant differences in odds for responding "yes" to the topics "show patients proper tooth brushing (and flossing) techniques" and "managing dry mouth" (Ps = 0.02). However, management of dry mouth, demonstrations and return demonstrations of oral hygiene techniques were covered by 27.0%, 10.1% and < 1% programs, respectively. PMID- 21030101 TI - Remission of diabetes mellitus type 2 with severe hyperglycemia after Exenatide treatment. AB - A 54-year-old obese woman with poorly controlled type 2 diabetes was put on the maximum allowed doses of Metformin, Glimepiride and Rosiglitazone. When Exenatide was added, she lost 33 kg. She remained euglycemic for at least 7 months after the sequential discontinuation of Exenatide and the other oral agents. PMID- 21030102 TI - Fasting blood glucose and diagnosis of type 2 diabetes. PMID- 21030103 TI - Efficacy of occasional self-monitoring of postprandial blood glucose levels in type 2 diabetic patients without insulin therapy. PMID- 21030104 TI - Is endovascular revascularisation worthwhile in diabetic patients with critical limb ischemia who also have end-stage renal disease? AB - To present the outcomes of endovascular treatment of diabetics patients with critical limb ischemia who have end-stage renal disease. Limb-salvage was achieved in 58.6% of the limbs during a mean follow-up period of 12.4 months. No major amputations were required on patients with rest pain or with grade 1 lesions. PMID- 21030105 TI - Entecavir treatment in patients with severe acute exacerbation of chronic hepatitis B. AB - BACKGROUND & AIMS: Severe acute exacerbation of chronic hepatitis B is a unique clinical presentation with significant morbidity and mortality. Lamivudine was used in most previous studies, but the drug was limited by the development of resistance. Our objective is to study the safety and efficacy of entecavir in patients with severe acute exacerbation. METHODS: Consecutive patients with severe acute exacerbation of chronic hepatitis B were recruited from 1998 to 2009. All patients had serum alanine aminotransferase and bilirubin increased beyond 10 and 3 times the upper limit of normal, respectively. The primary endpoint was overall mortality at week 48. Virological and biochemical responses were also studied. RESULTS: Thirty-six patients and 117 patients were treated with entecavir and lamivudine, respectively. By week 48, 7 (19%) patients in the entecavir group and 5 (4%) patients in the lamivudine group died (adjusted hazard ratio 5.1, 95% confidence interval 1.5-17.2, p=0.010). Similarly, the entecavir group had higher liver-related mortality (adjusted hazard ratio 4.0, 95% confidence interval 1.0-15.7, p=0.044). Despite a lower prevalence of cirrhosis, more patients in the entecavir group developed prolonged jaundice, hepatic encephalopathy, and ascites. Entecavir resulted in more rapid and complete viral suppression, with 71% of patients achieving undetectable hepatitis B virus (HBV) DNA at week 48, compared to 40% in the lamivudine group (p=0.007). However, rapid HBV DNA reduction at week 4 was associated with prolonged jaundice. CONCLUSIONS: Entecavir treatment is associated with increased short-term mortality in patients with severe acute exacerbation of chronic hepatitis B but achieves better virological response in the long run. PMID- 21030106 TI - Evaluation and equity audit of the domestic radon programme in England. AB - The U.K. has a radon programme to limit the radon risk to health. This involves advice on protective measures in new buildings, technical guidance on their installation, encouragement of radon measurements and remediation in existing dwellings in high radon areas. We have audited the radon programme at the level of individual homes to identify factors that influence the likelihood of remediation. 49% of the householders responded to our survey and 30% of the respondents stated that they had done some remediation to reduce the indoor radon levels. We found that householders with higher incomes and higher socio-economic status are more likely than others to remediate. Householders are less likely to remediate if they have one of the following: living in a property with a high radon concentration, current smokers in the dwelling, being unemployed or an unskilled worker, long length of time living in that property or elderly (65+ years) living by themselves. Householders appeared to be more likely to remediate if they considered the information on radon and its risk to be very clear and useful. This emphasises the importance of communication with householders. PMID- 21030107 TI - Multi-sector policy action to create activity-friendly environments for children: a multiple-case study. AB - OBJECTIVES: The aim of this study is (1) to gain insight into current multi sector policy initiatives that contribute to activity-friendly environments for children in four Dutch municipalities, (2) to investigate the role of multi sector collaboration in multi-sector policy action and (3) to gain insight into critical facilitators and possible challenges for multi-sector policy action aimed at creating activity-friendly environments for children. METHODS: A policy analysis was conducted in four Dutch municipalities by means of semi-structured interviews with 25 policy officers from different policy sectors. Interviews were transcribed ad verbatim and analyzed using qualitative data coding software. RESULTS: Each policy sector carried out policy measures related to (the environmental determinants of) physical activity among children, but most respondents were not aware of the potential effectiveness of their policy measures regarding this topic. In two municipalities structural collaboration between policy sectors was present, but the number of sectors involved was limited. Awareness and support among all policy sectors, a stimulating political environment, and knowing each other and being informed about other sectors' policies were mentioned as facilitators for multi-sector policy action. The main challenge for multi-sector policy action was lack of time and resources. CONCLUSIONS: This study shows that multi-sector policy action aimed at activity friendly environments could be stimulated by raising awareness and defining problem ownership, enhancing multi-sector collaboration and paying attention to facilitators and challenges. PMID- 21030109 TI - [Fibrovascular tissue of hydroxyapatite ocular implant visualized in SPECT-CT with Tc-99m biphosphonates]. PMID- 21030108 TI - Assessing chlorinated ethene degradation in a large scale contaminant plume by dual carbon-chlorine isotope analysis and quantitative PCR. AB - The fate of chlorinated ethenes in a large contaminant plume originating from a tetrachloroethene (PCE) source in a sandy aquifer in Denmark was investigated using novel methods including compound-specific carbon and chlorine isotope analysis and quantitative real-time polymerase chain reaction (qPCR) methods targeting Dehaloccocoides sp. and vcrA genes. Redox conditions were characterized as well based on concentrations of dissolved redox sensitive compounds and sulfur isotopes in SO(4)(2-). In the first 400 m downgradient of the source, the plume was confined to the upper 20 m of the aquifer. Further downgradient it widened in vertical direction due to diverging groundwater flow reaching a depth of up to 50 m. As the plume dipped downward and moved away from the source, O(2) and NO(3)(-) decreased to below detection levels, while dissolved Fe(2+) and SO(4)(2-) increased above detectable concentrations, likely due to pyrite oxidation as confirmed by the depleted sulfur isotope signature of SO(4)(2-). In the same zone, PCE and trichloroethene (TCE) disappeared and cis-1,2-dichloroethene (cDCE) became the dominant chlorinated ethene. PCE and TCE were likely transformed by reductive dechlorination rather than abiotic reduction by pyrite as indicated by the formation of cDCE and stable carbon isotope data. TCE and cDCE showed carbon isotope trends typical for reductive dechlorination with an initial depletion of (13)C in the daughter products followed by an enrichment of (13)C as degradation proceeded. At 1000 m downgradient of the source, cDCE was the dominant chlorinated ethene and had reached the source delta(13)C value confirming that cDCE was not affected by abiotic or biotic degradation. Further downgradient (up to 1900 m), cDCE became enriched in (13)C by up to 8 0/00 demonstrating its further transformation while vinylchloride (VC) concentrations remained low (<1 MUg/L) and ethene was not observed. The correlated shift of carbon and chlorine isotope ratios of cDCE by 8 and 3.9 0/00, respectively, the detection of Dehaloccocides sp genes, and strongly reducing conditions in this zone provide strong evidence for reductive dechlorination of cDCE. The significant enrichment of (13)C in VC indicates that VC was transformed further, although the mechanism could not be determined. The transformation of cDCE was the rate limiting step as no accumulation of VC occurred. In summary, the study demonstrates that carbon chlorine isotope analysis and qPCR combined with traditional approaches can be used to gain detailed insight into the processes that control the fate of chlorinated ethenes in large scale plumes. PMID- 21030110 TI - Prevalence of virulence genes among invasive and colonising Staphylococcus aureus isolates. PMID- 21030111 TI - Clusters of infection due to metallo-beta-lactamase-producing Pseudomonas aeruginosa in stem cell transplant and haematology units. PMID- 21030112 TI - Mortality in patients with meticillin-resistant Staphylococcus aureus bacteraemia, England 2004-2005. AB - A population-based study was undertaken to determine the short term risk of death in English patients diagnosed with meticillin-resistant Staphylococcus aureus (MRSA) bacteraemia. All patients with an MRSA-positive blood culture taken in 2004 and 2005 in England identified through routine surveillance were matched to the national registry of deaths. The study found an overall case fatality (all cause) within 7 days of MRSA-positive blood culture diagnosis of 20%, rising to 38% within 30 days. Risk of death was highest on the day subsequent to the blood specimen being drawn (4%). Seven-day case fatality rates in women were 16% higher than for men (odds ratio: 1.16; 95% confidence interval: 1.04-1.29), although no significant difference was discernable by day 30. Risk of death increased with rising age, with 28% (425/1513) of patients aged >=85 years dying within 7 days and 57% (859/1513) within 30 days. A seasonal pattern in case fatality rates was evident, highest in the winter and lowest in the summer. The age-standardised mortality ratios within the first week were 180 and 225 times as high for men and women, respectively, as for the general population. This declined rapidly after 10 weeks to approximately 9 for both sexes. An estimated 5.53 deaths per 100,000 population followed MRSA bacteraemia in 2004 and 2005, although no inference on causality or attributable mortality could be made through this study. The stable, elevated risk of death observable after 10 weeks compared with that in the general population gave an indication of the background risk of death unrelated to MRSA infection. PMID- 21030113 TI - Rapid detection of aortic occlusion with emergency ultrasonography. AB - The differential diagnosis of aortic emergencies includes abdominal aortic aneurysms and aortic dissection. Aortic occlusion is another rare yet deadly vascular emergency to be wary of. For acute occlusions, definitive management by embolectomy or aortofemoral bypass must be performed promptly. When suspected because of the history and physical examination results, bedside ultrasonography rapidly confirms the diagnosis. We describe 2 very different cases of aortic occlusion both initially detected with bedside ultrasonography in our emergency department. PMID- 21030114 TI - "Somebody else's problem?" Staff perceptions of the sources and control of meticillin-resistant Staphylococcus aureus. AB - BACKGROUND: Meticillin-resistant Staphylococcus aureus (MRSA) is endemic within the United Kingdom health care sector. Recent campaigns to reduce health care associated infection have rested on increasing staff accountability and ownership of the problem and its solutions. However, the existence of reservoirs of colonization in the community now creates ambiguity about sources, which may undermine preventative strategies. METHODS: The theoretical framework of causal attribution was applied to explore staff biases in perceptions and effects on infection control behaviors on both sides of the hospital/care home interface. Forty-four staff from 1 acute care hospital and 53 staff from 6 care homes estimated prevalence, risk, and sources of MRSA. Focus groups (6 care home and 8 hospital) were used to elicit group perceptions. RESULTS: Staff tended to attribute the causes of MRSA to external (not self) human factors including patient risk factors and poor infection control practices of others. Teams tend to attribute their "successes" in infection control to dispositional attributions (good team policy and performance) and attribute "lapses" to situational factors (client group, patient movement, work pressures). CONCLUSION: Variations in information needs, ownership, and infection control practices could be addressed by better interorganizational working and support for staff teams to assess their own responses to the problem. PMID- 21030115 TI - Synaptic correlates of memory and menopause in the hippocampal dentate gyrus in rhesus monkeys. AB - Aged rhesus monkeys exhibit deficits in hippocampus-dependent memory, similar to aging humans. Here we explored the basis of cognitive decline by first testing young adult and aged monkeys on a standard recognition memory test (delayed nonmatching-to-sample test; DNMS). Next we quantified synaptic density and morphology in the hippocampal dentate gyrus (DG) outer (OML) and inner molecular layer (IML). Consistent with previous findings, aged monkeys were slow to learn DNMS initially, and they performed significantly worse than young subjects when challenged with longer retention intervals. Although OML and IML synaptic parameters failed to differ across the young and aged groups, the density of perforated synapses in the OML was coupled with recognition memory accuracy. Independent of chronological age, monkeys classified on the basis of menses data as peri- or post-menopausal scored worse on DNMS, and displayed lower OML perforated synapse density, than premenopausal monkeys. These results suggest that naturally occurring reproductive senescence potently influences synaptic connectivity in the DG OML, contributing to individual differences in the course of normal cognitive aging. PMID- 21030116 TI - [Confusion in a 60-year-old man]. PMID- 21030117 TI - [Systemic lupus and biotherapy: 2010 update]. PMID- 21030118 TI - Regional-scale application of the decision support system MOIRA-PLUS: an example of assessment of the radiological impact of the Chernobyl accident on the fresh water ecosystem in Italy. AB - The present work illustrates the customisation and application of the decision support system MOIRA-PLUS (a MOdel-based computerised system for management support to Identify optimal remedial strategies for Restoring radionuclide contaminated Aquatic ecosystems and drainage areas) to the fresh water environment in Italy. MOIRA-PLUS is aimed at evaluating the behaviour of radiocaesium and radiostrontium in fresh water ecosystems and at assessing the appropriateness of suitable strategies for the management of contaminated water bodies by the application of multi-attribute analysis techniques. MOIRA-PLUS can be applied to complex networks of lakes, rivers and tributaries and can be straightforwardly customised utilising data and information from readily accessible sources such as official websites provided by scientific or government organisations. The present work shows an application of the decision system to 10 lakes and 18 rivers in Italy contaminated with (137)Cs of Chernobyl origin. Site specific values of some aggregated transfer parameters were estimated for the most important Italian lakes. Although high values of fish and water consumptions were hypothesised, very low doses to public from the fresh water pathway following the accident were calculated. PMID- 21030119 TI - Monitoring of intraoral free flaps with microdialysis. AB - Because of the confined nature of their position, monitoring intraoral free flaps is a challenge, but it is essential to detect vascular complications in time to ensure the possibility of salvaging the flap. Microdialysis has been the standard technique of choice at the Department of Plastic Surgery, Aarhus University Hospital, since September 1998. In this study we present our experience of monitoring 78 intraoral free flaps. It is a retrospective evaluation of patients' casenotes from November 1998 to March 2008. Sixty-five of the 78 flaps healed without complications. Sixty-one of these showed no sign of ischaemia in the microdialysis values; in 4 cases the microdialysis system caused technical problems. Thirteen patients were reoperated on based on the results of microdialysis analysis, and in all but 2 cases critical ischaemia was found. Ten of the 11 critically ischaemic flaps were saved. The overall loss rate of flaps was 1.3%. The 2 flaps that were reoperated on but no critical ischaemia found were 2 fibular flaps during the time that we were learning how to monitor with microdialysis (1999 and 2000). Since then we have developed a decision algorithm for standard monitoring, and since 2000 we have had no false positive results. We have never lost a flap from neglected ischaemia. Our results show that microdialysis is a safe and reliable technique for postoperative monitoring of intraoral free flaps. PMID- 21030120 TI - Controversies surrounding iron chelation therapy for MDS. AB - The myelodysplastic syndromes (MDS) are characterized by cytopenias and acute myeloid leukemia risk. Most MDS patients eventually require transfusion of red blood cells for anemia, placing them at risk of iron overload (IOL). In beta thalassemia major, transfusional IOL leads to organ dysfunction and death, however, with iron chelation therapy survival improved to near normal and organ function was improved. In lower risk MDS, several non-randomized studies suggest an adverse effect of IOL on survival, and that lowering iron minimizes this impact and may improve organ function. While guidelines for MDS generally recommend chelation in selected lower risk patients, data are emerging suggesting IOL may impact adversely on the outcome of higher risk MDS and stem cell transplantation (SCT) and that lowering iron may be beneficial in these patients. Trials to determine whether these effects are truly from lowering iron are currently enrolling. Chelation is costly and potentially toxic, and in MDS should be initiated after weighing potential risks and benefits for each patient until more definitive data are available. In this paper, data on the impact of IOL in MDS and SCT, possible mechanisms of iron toxicity such as oxidative stress, and the impact of lowering iron on organ function and survival are reviewed. PMID- 21030121 TI - Venous access in the management of hemophilia. AB - Venous access is an essential aspect of hemophilia care. When peripheral venipuncture is not feasible, central venous access devices (CVADs) or the creation of an arteriovenous fistula (AVF) allow the infusion of clotting factor concentrate to treat or prevent bleeding events or eliminate inhibitors. Infection is the primary complication associated with CVADs and the most common reason for their removal. Complications of AVF include occlusion and limb length discrepancies. PMID- 21030122 TI - The relationships between air pollutants, meteorological parameters and concentration of airborne fungal spores. AB - Fungal spores are an important component of bioaerosol and also considered to act as indicator of the level of atmospheric bio-pollution. Therefore, better understanding of these phenomena demands a detailed survey of airborne particles. The objective of this study was to examine the dependence of two the most important allergenic taxa of airborne fungi--Alternaria and Cladosporium--on meteorological parameters and air pollutant concentrations during three consecutive years (2006-2008). This study is also an attempt to create artificial neural network (ANN) forecasting models useful in the prediction of aeroallergen abundance. There were statistically significant relationships between spore concentration and environmental parameters as well as pollutants, confirmed by the Spearman's correlation rank analysis and high performance of the ANN models obtained. The concentrations of Cladosporium and Alternaria spores can be predicted with quite good accuracy from meteorological conditions and air pollution recorded three days earlier. PMID- 21030123 TI - Concept mapping of diet and physical activity: uncovering local stakeholders perception in the Quebec City region. AB - Overweight and obesity are major public health concerns that are neither evenly distributed among the population nor between regions. Many studies suggest that beyond individual characteristics, the place where one lives influences lifestyle choices that underpin overweight and obesity. We observed such a situation in the province of Quebec (Canada), and because data availability from surveys was limited to a local level, the observed overweight disparities between local communities could not be entirely explained. Aiming to uncover local factors not captured by national survey data sets and in order to aid local level intervention, we investigated how the overweight problem was perceived by stakeholders through a concept mapping methodology. Concept mapping is a mixed method that relies upon stakeholders' perception as well as statistical techniques to draw a synthesis of the problem in the form of a conceptual map. A total of 45 stakeholders working in four areas with contrasting overweight prevalence in the Quebec City region were involved in the process. The map enables a global understanding of stakeholders' perception. This perception is not necessarily in line with public health knowledge however. For example, key concepts on the map suggest that physical activity is perceived to be much more important than diet with regards to population overweight and that urban design elements seem to be of low concern. Concept mapping is an innovative tool for planning and evaluation and can help stakeholders to develop adapted interventions to promote healthy lifestyle. It also provides relevant information to enhance the comprehension of local health disparities with a geographical perspective where data availability is limited. PMID- 21030124 TI - Survey of faculty educator development award recipients. AB - PURPOSE: Since 2002, the American Association of Oral and Maxillofacial Surgeons and the Oral and Maxillofacial Surgery Foundation have annually awarded the Faculty Educator Development Award (FEDA) to select junior full-time oral and maxillofacial surgery faculty. To date, 33 individuals have received this award. The purpose of this study was to evaluate the FEDA's impact on the recipients' career and assess the FEDA's strengths and weaknesses from the perspective of the recipients. MATERIALS AND METHODS: A complete list of FEDA recipients was obtained from the American Association of Oral and Maxillofacial Surgeons, to whom a 19-question survey was electronically mailed for completion. RESULTS: Twenty-two of the 33 surveys were completed and returned. Strengths of the FEDA included encouraging faculty recruitment and retention and financial support. Weaknesses included unknown selection criteria for the FEDA, unknown FEDA selection committee, and that the financial component of the award was available for only 3 of the 6 years of the FEDA requirement. CONCLUSION: Although there are some weaknesses in the FEDA, it is the only award of its kind available to the specialty of oral and maxillofacial surgery. As such, consideration should be given to expanding the number of awards given and increasing the amount of the award. In addition, academic oral and maxillofacial surgery needs to improve its recruitment and retention of junior surgical faculty to ensure the continued viability of the specialty and training programs. Suggestions for improvement are discussed. PMID- 21030125 TI - Use of the acetabular reamer for corticocancellous bone harvest from the posterior iliac crest: a preliminary report. PMID- 21030126 TI - Reconstruction of subtotal defects of the lower lip: a review of current techniques and a proposed modification. PMID- 21030127 TI - Vanishing bone disease: a review. PMID- 21030128 TI - Basosquamous carcinoma involving the anterior skull base: a neglected tumor treated using intraoperative navigation as a guide to achieve safe resection margins. AB - Basosquamous carcinoma (BSC) or metatypical carcinoma is a rare and controversial form of basal cell carcinoma (BCC) that was first described by MacCormac in 1910. Numerous theories have been described in the literature regarding its origin but it is generally accepted as a variant of BCC that differentiates into squamous cell carcinoma (SCC). At present, it has an unsatisfactorily established phenotype but is considered to behave more like an SCC than a BCC. A reflection of this fact is its more aggressive nature with a significantly increased incidence of local and distant metastasis. It must be distinguished histologically from so-called "collision" tumors, which represent SCC and BCC arising as separate entities in the same area. We present a unique case of a neglected, large, and locally advanced case of BCC originating from the nose, but extending into the paranasal sinuses, orbit, and anterior skull base, that was treated with en bloc surgical resection using intraoperative navigation to assist in treatment planning and margin clearance. PMID- 21030129 TI - An "extra hand" in the office. PMID- 21030130 TI - The effect of attending to motor overflow on its voluntary inhibition in young and older adults. AB - Motor overflow refers to involuntary movement or muscle activity coinciding with voluntary movement. We examined whether 16 young adults (18-30 years) and 16 older adults (50-80 years) could voluntarily inhibit overflow. Participants performed a finger pressing task, exerting 50% of their maximal force. Overflow was concurrently recorded in the non-task hand. In the first condition, participants were not made aware of their motor overflow. Then participants, though informed of it, were asked to ignore their overflow. Finally, participants were requested to inhibit overflow with, and then without visual feedback, or vice versa. Overflow was exacerbated when older adults were unaware of it, and was reduced once they were informed. For young adults there was no significant difference between these conditions. Both Age Groups could significantly reduce overflow when so requested, independent of visual feedback. Thus motor overflow can be modulated by higher order cognitive control with directed attention. PMID- 21030131 TI - [Resurfacing of a trochanteric pressure sore by a pedicled fasciocutaneous anterolateral thigh flap: a case report]. AB - The anterolateral thigh flap is usually used as a free flap for various kinds of reconstruction and resurfacing of distant areas. Cover of a deep trochanteric pressure sore is commonly made by muscular or musculocutaneous flaps such as tensor of fascia lata or vastus lateralis. We report the case of a trochanteric pressure sore covered by a fasciocutaneous pedicled anterolateral thigh flap after negative pressure therapy in a 58-year-old paraplegic patient. After 6 months, a good quality of coverage was obtained with minimal morbidity of donor site. The pedicled fasciocutaneous anterolateral flap appears as a reliable option for the treatment of trochanteric pressure sore. PMID- 21030132 TI - Experimental endometriosis reduction in rats treated with Uncaria tomentosa (cat's claw) extract. AB - OBJECTIVE: The aim of this study was to analyze the macroscopic and histological changes that occur in experimental endometriosis after treatment with Uncaria tomentosa. STUDY DESIGN: Experimental endometriosis was induced in twenty-five female Wistar rats. After three weeks, 24 animals developed grade III experimental endometriosis and were divided into two groups. Group "U" received U. tomentosa extract orally (32 mg/day), and group "C" (control group) received a 0.9% sodium chloride solution orally (1 ml/100g of body weight/day). Both groups were treated with gavage for 14 days. At the surgical intervention and after the animal was euthanized, the implant volume was calculated with the following formula: [4pi (length/2)*(width/2)*(height/2)/3]. The autotransplants were removed, dyed with hematoxylin-eosin, and analyzed by light microscopy. The Mann Whitney test was used for the independent samples, and the Wilcoxon test analyzed the related samples, with a significance level of 5%. RESULTS: The difference between the initial average volumes of the autotransplants was not significant between the groups (p = 0.18). However, the final average volumes were significantly different between the groups (p = 0.001). There was a significant increase (p = 0.01) between the initial and final average volumes in the control group, and treatment with the U. tomentosa caused a marked reduction in the growth over time (p = 0.009). Histologically, in the experimental group (n = 10) six rats had a well-preserved epithelial layer, three had mildly preserved epithelium, and one had poorly preserved epithelium. The epithelial layer occasionally presented sporadic epithelial cells. The control group (n = 12) presented seven cases (58.3%) of well-preserved epithelial cells and five cases (41.7%) of mildly preserved epithelial cells. CONCLUSIONS: Cat's claw extract appears to be a promising alternative for treating endometriosis. PMID- 21030133 TI - Trade transport and environment linkages at the U.S.-Mexico border: which policies matter? AB - We apply a fixed-effects model to examine the impact of trade and environmental policies on air quality at ports along the U.S.-Mexico border. We control for other factors influencing air quality, such as air quality of cities near the border, volume of traffic flows and congestion. Results show the air quality improved after 2004, when the diesel engine policy was applied. We see mixed results for the trade policy, whose implementation time varies across ports along the international border. Controlling for air quality in cities near the border is essential for assessing the policy contributions to air quality. PMID- 21030134 TI - Combining steam injection with hydraulic fracturing for the in situ remediation of the unsaturated zone of a fractured soil polluted by jet fuel. AB - A steam injection pilot-scale experiment was performed on the unsaturated zone of a strongly heterogeneous fractured soil contaminated by jet fuel. Before the treatment, the soil was stimulated by creating sub-horizontal sand-filled hydraulic fractures at three depths. The steam was injected through one hydraulic fracture and gas/water/non-aqueous phase liquid (NAPL) was extracted from the remaining fractures by applying a vacuum to extraction wells. The injection strategy was designed to maximize the heat delivery over the entire cell (10 m * 10 m * 5 m). The soil temperature profile, the recovered NAPL, the extracted water, and the concentrations of volatile organic compounds (VOCs) in the gas phase were monitored during the field test. GC-MS chemical analyses of pre- and post-treatment soil samples allowed for the quantitative assessment of the remediation efficiency. The growth of the heat front followed the configuration of hydraulic fractures. The average concentration of total hydrocarbons (g/kg of soil) was reduced by ~ 43% in the upper target zone (depth = 1.5-3.9 m) and by ~ 72% over the entire zone (depth = 1.5-5.5 m). The total NAPL mass removal based on gas and liquid stream measurements and the free-NAPL product were almost 30% and 2%, respectively, of those estimated from chemical analyses of pre- and post treatment soil samples. The dominant mechanisms of soil remediation was the vaporization of jet fuel compounds at temperatures lower than their normal boiling points (steam distillation) enhanced by the ventilation of porous matrix due to the forced convective flow of air. In addition, the significant reduction of the NAPL mass in the less-heated deeper zone may be attributed to the counter current imbibition of condensed water from natural fractures into the porous matrix and the gravity drainage associated with seasonal fluctuations of the water table. PMID- 21030136 TI - Two-dimensional flow index mapping for hemodynamic imaging: a feasibility study. AB - The resistive index (RI) is a functional hemodynamic index used to measure flow resistance within an organ, such as the kidney, to assess if there is any vascular disease associated with that organ. Currently, the measurement of RI values using spectral Doppler ultrasound (US) is performed in one location at a time. As a result, RI values are typically obtained only from a few locations. To visualize the entire two-dimensional distribution of RI values, we developed a method called two-dimensional flow index mapping (2D-FIM). To evaluate this method, we performed a feasibility study using 16 kidney data sets, with eight from healthy volunteers with normal native kidneys and eight from kidney transplant recipients. Quadrature-demodulated baseband Doppler data were used to calculate the spatial distribution of RI values using 2D-FIM. For comparison, the intrarenal RI values at different levels of renal arterial branches were measured with conventional spectral Doppler US. The RI values determined from 2D-FIM were compared with those from spectral Doppler US, which led to a Pearson correlation coefficient of 0.84. There was no significant difference between 2D-FIM- and spectral Doppler US-produced RI values. With the ability to visualize RI in more than one dimension, 2D-FIM could help guide placement of the spectral Doppler range gate to regions of abnormal RI, thus potentially reducing exam times. PMID- 21030137 TI - On sizing and counting of microbubbles using optical microscopy. AB - Intra- and interobserver (n = 3) variability of sizing and counting microbubbles using optical microscopy (OM) was assessed. The system was calibrated using standardised mono-disperse and poly-disperse microspheres. Results of the calibration show intraobserver variations of number count (C) = 13.0% and arithmetic mean size (MS) = 0.2%, and interobserver variations of C = 18.4% and MS = 0.6%, for the mono-disperse microspheres. For the poly-disperse microspheres, intraobserver variations were: C = 6.9% and MS = 0.8%, and interobserver: C = 10.5% and MS = 0.3%. For SonoVueTM the intraobserver variations were: C = 23.3% and MS = 8.0%, and interobserver C = 6.8% and MS = 3.8%. The results suggest that the higher values of the intraobserver variation for SonoVueTM arise from the natural decay of microbubbles over time. This article presents a detailed protocol and outlines potential pitfalls in our approach. These results are in general agreement with those previously reported and compare well with known size distributions. PMID- 21030138 TI - B-lines quantify the lung water content: a lung ultrasound versus lung gravimetry study in acute lung injury. AB - B-lines (also termed ultrasound lung comets) obtained with lung ultrasound detect experimental acute lung injury (ALI) very early and before hemogasanalytic changes, with a simple, noninvasive, nonionizing and real-time method. Our aim was to estimate the correlation between B-lines number and the wet/dry ratio of the lung tissue, measured by gravimetry, in an experimental model of ALI. Seventeen Na-pentobarbital anesthetized, cannulated (central vein and carotid artery) minipigs were studied: five sham-operated animals served as controls and, in 12 animals, ALI was induced by injection of oleic acid (0.1 mL/kg) via the central venous catheter. B-lines were measured by echographic scanner in four predetermined chest scanning sites in each animal. At the end of each experiment, both lungs were dissected, weighed and dried to determine wet/dry weight ratio by gravimetry. After the injection of oleic acid, B-lines number increased over time. A significant correlation was found between the wet/dry ratio and B-lines number (r = 0.91, p < 0.001). These data suggest that in an experimental pig model of ALI/ARDS, B-lines assessed by lung ultrasound provide a simple, semiquantitative, noninvasive index of lung water accumulation, strongly correlated to invasive gravimetric assessment. PMID- 21030139 TI - Pulsatility index change of brachial artery shows better reproducibility than flow-mediated vasodilation. AB - We aim to evaluate intra- and interobserver reproducibility of brachial artery flow-mediated dilation (FMD) and of pulsatility index change (PI-C) 1 min after a 5-min forearm compression in pregnant women. Flow-mediated dilation and PI-C were assessed in 31 healthy pregnant women in 3 consecutive days, by two observers. A broader range of response to the stimulus was observed for PI-C (-58.99%-86.71%) than FMD (2.38%-27.01%). The intraclass correlation coefficients were higher for PI-C than for FMD (intra = 0.90 vs. 0.69, p = 0.047; inter = 0.94 vs. 0.61, p = 0.007). Therefore, PI-C measurements were more reliable than FMD. However, studies comprising of subjects with cardiovascular risk factors relating FMD and PI-C become necessary to validate this method for the study of endothelial dysfunction. PMID- 21030140 TI - Nonlinear shell behavior of phospholipid-coated microbubbles. AB - The influence of the stabilizing phospholipid-coating on the nonlinear dynamics of ultrasound contrast agent microbubbles is investigated. We record the radial dynamics of individual microbubbles with an ultra high-speed camera as a function of both driving pressure and frequency. The viscoelastic shell was found to enhance the nonlinear bubble response at acoustic pressures as low as 10 kPa. For increasing acoustic pressures a decrease of the frequency of maximum response was observed for a distinct class of bubbles, leading to a pronounced skewness of the resonance curve, which we show to be the origin of the "thresholding" behavior (Emmer et al. 2007). For the other bubbles, the frequency of maximum response was found to lie just above the resonance frequency of an uncoated microbubble and to be independent of the applied acoustic pressure. The shell-buckling bubble model (Marmottant et al. 2005), which accounts for buckling and rupture of the shell, captures both cases for a unique set of the shell parameters, the relevant parameter being the phospholipid concentration at the bubble interface. PMID- 21030141 TI - Slip imaging: reducing ambiguity in breast lesion assessment. AB - Ultrasound elasticity imaging (elastography) is gaining popularity as an adjunct to B-mode ultrasound for breast cancer diagnosis. Cancerous masses are usually stiffer than normal tissue, hence, using elasticity imaging should lead to better differentiation between benign and malignant masses than using B-mode alone. Clinicians assess the mobility of masses on palpation; cancers usually being less mobile. We introduce a method to estimate mobility, called slip imaging and combine it with conventional B-mode and elasticity data. In the reported evaluation on 70 women recalled to a breast assessment clinic, images were scored by three breast radiologists independently. Diagnostic accuracy increased from 75.7% with B-mode alone, to 78.1% when including elasticity imaging, to 80.0% when further including slip imaging. Specificity increased (74.6%:75.4%:82.5% respectively), with an apparent trade-off in sensitivity (77.1%:81.3%:77.1%). We conclude that Slip imaging is potentially a useful adjunct to B-mode and elasticity imaging and should undergo further research and development. PMID- 21030143 TI - Is there a need to further subclassify pT2 renal cell cancers as implemented by the revised 7th TNM version? AB - BACKGROUND: The recently modified TNM classification of renal cell carcinoma (RCC) (7th edition) has implemented a subdivision of pT2 tumours into stage pT2a (>7 or <=10 cm) versus pT2b disease (>10 cm). OBJECTIVE: Our aim was to evaluate whether this subdivision of pT2 RCC is justified due to a clinical prognosis divergence between the two groups (pT2a vs pT2b) DESIGN, SETTING, AND PARTICIPANTS: In total, 5122 patients were subjected to either radical nephrectomy or nephron-sparing surgery at three centres in Germany (University Hospitals of Hannover, Homburg/Saar, and Marburg). Patients were reclassified into stage pT2a and pT2b according to the maximum tumour diameter as suggested by the 7th revised version of the TNM classification system. MEASUREMENTS: The t test and Fisher exact test were applied to evaluate the comparability of the two groups (pT2a vs pT2b) regarding several additional patients' and tumour-specific characteristics of known prognostic relevance for RCC. Univariable (Kaplan-Meier analysis) and multivariable statistical analyses (Cox proportional hazards regression model) were applied to identify a possible difference between the two groups (pT2a vs pT2b) regarding cancer-specific survival (CSS). RESULTS AND LIMITATIONS: Applying the new TNM classification, 579 previously pT2-staged patients were divided into 445 (76.9%) with pT2a and 134 (23.1%) with pT2b tumours. Kaplan-Meier curves revealed no significant difference in CSS between pT2a and pT2b patients; 5-yr CSS was 79.0% and 74.1%, respectively (p=0.38). When applying multivariable analysis, unlike tumour grade and N/M status, pT2 subclassification failed to independently predict survival in RCC patients. CONCLUSIONS: The new subclassification of pT2 RCC into two different subgroups as suggested by the latest modification of the TNM system does not yield additional/prognostic information. PMID- 21030142 TI - A tissue phantom for visualization and measurement of ultrasound-induced cavitation damage. AB - Many ultrasound studies involve the use of tissue-mimicking materials to research phenomena in vitro and predict in vivo bioeffects. We have developed a tissue phantom to study cavitation-induced damage to tissue. The phantom consists of red blood cells suspended in an agarose hydrogel. The acoustic and mechanical properties of the gel phantom were found to be similar to soft tissue properties. The phantom's response to cavitation was evaluated using histotripsy. Histotripsy causes breakdown of tissue structures by the generation of controlled cavitation using short, focused, high-intensity ultrasound pulses. Histotripsy lesions were generated in the phantom and kidney tissue using a spherically focused 1-MHz transducer generating 15 cycle pulses, at a pulse repetition frequency of 100 Hz with a peak negative pressure of 14 MPa. Damage appeared clearly as increased optical transparency of the phantom due to rupture of individual red blood cells. The morphology of lesions generated in the phantom was very similar to that generated in kidney tissue at both macroscopic and cellular levels. Additionally, lesions in the phantom could be visualized as hypoechoic regions on a B-mode ultrasound image, similar to histotripsy lesions in tissue. High-speed imaging of the optically transparent phantom was used to show that damage coincides with the presence of cavitation. These results indicate that the phantom can accurately mimic the response of soft tissue to cavitation and provide a useful tool for studying damage induced by acoustic cavitation. PMID- 21030144 TI - Duloxetine for mild to moderate postprostatectomy incontinence: preliminary results of a randomised, placebo-controlled trial. AB - BACKGROUND: Duloxetine is effective in the management of stress urinary incontinence (SUI) in women but has been poorly evaluated in the treatment of SUI following radical prostatectomy (RP). OBJECTIVE: To establish the superiority of duloxetine over placebo in SUI after RP. DESIGN, SETTING, AND PARTICIPANTS: We conducted a prospective, randomised, placebo-controlled, double-blind, monocentric superiority trial. After a placebo run-in period of 2 wk, patients with SUI after RP were randomised to receive either 80mg of duloxetine daily or matching placebo for 3 mo. MEASUREMENTS: The primary outcome measure was the relative variation in incontinence episodes frequency (IEF) at the end of study compared to baseline. Secondary outcomes included quality of life (QoL) measures (Incontinence Impact Questionnaire Short Form [IIQ-SF], Urogenital Distress Inventory Short Form [UDI-SF], Incontinence Quality of Life [I-QoL]), symptom scores (Urinary Symptom Profile [USP] questionnaire, International Consultation on Incontinence/World Health Organisation Short Form questionnaire [ICIQ-SF], the Beck Depression Inventory [BDI-II] questionnaire), 1-h pad test, and assessment of adverse events. RESULTS AND LIMITATIONS: Thirty-one patients were randomised to either the treatment (n=16) or control group (n=15). Reduction in IEF was significant with duloxetine compared to placebo (mean+/-standard deviation [SD] variation: -52.2%+/-38.6 [range: -100 to +46] vs +19.0%+/-43.5 [range: -53 to +104]; mean difference: 71.2%; 95% confidence interval [CI] for the difference: 41.0-101.4; p<0.0001). IIQ-SF total score, UDI-SF total score, SUI subscore of the USP questionnaire, and question 3 of the ICIQ-SF questionnaire showed improvement in the duloxetine group (p=0.006, p=0.02, p=0.0004, and p=0.003, respectively). Both treatments were well tolerated throughout the study period. CONCLUSIONS: Duloxetine is effective in the treatment of incontinence symptoms and improves QoL in patients with SUI after RP. PMID- 21030145 TI - Central fever as an early predictor of vasospasm in a child with isolated intraventricular hemorrhage. PMID- 21030146 TI - Synthesis of hierarchical Ni(OH)(2) and NiO nanosheets and their adsorption kinetics and isotherms to Congo red in water. AB - Ni(OH)(2) and NiO nanosheets with hierarchical porous structures were synthesized by a simple chemical precipitation method using nickel chloride as precursors and urea as precipitating agent. The as-prepared samples were characterized by X-ray diffraction, scanning electron microscopy and nitrogen adsorption-desorption isotherms. Adsorption of Congo red (CR) onto the as-prepared samples from aqueous solutions was investigated and discussed. The pore structure analyses indicate that Ni(OH)(2) and NiO nanosheets are composed of at least three levels of hierarchical porous organization: small mesopores (ca. 3-5 nm), large mesopores (ca. 10-50 nm) and macropores (100-500 nm). The equilibrium adsorption data of CR on the as-prepared samples were analyzed by Langmuir and Freundlich models, suggesting that the Langmuir model provides the better correlation of the experimental data. The adsorption capacities for removal of CR was determined using the Langmuir equation and found to be 82.9, 151.7 and 39.7 mg/g for Ni(OH)(2) nanosheets, NiO nanosheets and NiO nanoparticles, respectively. Adsorption data were modeled using the pseudo-first-order, pseudo-second-order and intra-particle diffusion kinetics equations. The results indicate that pseudo second-order kinetic equation and intra-particle diffusion model can better describe the adsorption kinetics. The as-prepared Ni(OH)(2) and NiO nanosheets are found to be effective adsorbents for the removal of Congo red pollutant from wastewater as a result of their unique hierarchical porous structures and high specific surface areas. PMID- 21030147 TI - Decreasing biotoxicity of fume particles produced in welding process. AB - Welding fumes contain heavy metals, such as chromium, manganese, and nickel, which cause respiratory diseases and cancer. In this study, a SiO(2) precursor was evaluated as an additive to the shielding gas in an arc welding process to reduce the biotoxicity caused by welding fume particles. Transmission electron micrographic images show that SiO(2) coats on the surface of welding fume particles and promotes particle agglomeration. Energy dispersive X-ray spectroscopy further shows that the relative amount of silicon in these SiO(2) coated agglomerates is higher than in baseline agglomerates. In addition, Escherichia coli (E. coli) exposed to different concentrations of pure SiO(2) particles generated from the arc welding process exhibits similar responses, suggesting that SiO(2) does not contribute to welding fume particle toxicity. The trend of E. coli growth in different concentrations of baseline welding fume particle shows the most significant inhibition occurs in higher exposure concentrations. The 50% lethal logarithmic concentrations for E. coli in arc welding particles of baseline, 2%, and 4.2% SiO(2) precursor additives were 823, 1605, and 1800 mg/L, respectively. Taken together, these results suggest that using SiO(2) precursors as an additive to arc welding shielding gas can effectively reduce the biotoxicity of welding fume. PMID- 21030148 TI - Compositional and functional features of humic acid-like fractions from vermicomposting of sewage sludge and cow dung. AB - The chemical changes occurring in five different substrates of sewage sludge spiked with different proportions of cow dung after vermicomposting with Eisenia foetida for 90 days were investigated. Their humic acid-like (HAL) fractions were isolated to determine the elemental and functional composition, and structural and functional characteristics using ultraviolet/visible, Fourier transform infrared (FT-IR) and fluorescence spectroscopies and scanning electron microscopy. After vermicomposting, the total organic C and C/N ratio decreased, and the total extractable C and humic acid (HA) C increased in all substrates. In the HAL fractions, the C and H contents, C/N and C/O and aliphatic structures, proteinaceous components and carbohydrates decreased, while the O and N and acidic functional group contents and C/H ratio, aromaticity and polycondensation structures increased. Further, the results suggest that the addition of cow dung to sewage sludge could improve the quality of organic matter humification of the substrates. The structures of HAL fractions in vermicomposts resembled those typical of soil HA, especially the vermicompost of cow dung alone. Scanning electron microscopy showed the microstructure of HAL fraction in final product became close-grained and lumpy. Overall results indicate that vermicomposting was an efficient technology for promoting organic matter (OM) humification in sewage sludge and cow dung alone, as well as in mixtures of both materials, improving their quality and environmental safety as a soil OM resource for utilization as soil amendments. PMID- 21030149 TI - Evaluating the impact of water supply strategies on p-xylene biodegradation performance in an organic media-based biofilter. AB - The influence of water irrigation on both the long-term and short-term performance of p-xylene biodegradation under several organic loading scenarios was investigated using an organic packing material composed of pelletised sawdust and pig manure. Process operation in a modular biofilter, using no external water supply other than the moisture from the saturated inlet air stream, showed poor p xylene abatement efficiencies (~33 +/- 7%), while sustained irrigation every 25 days rendered a high removal efficiency (RE) for a critical loading rate of 120 g m(-3)h(-1). Periodic profiles of removal efficiency, temperature and moisture content were recorded throughout the biofilter column subsequent to each biofilter irrigation. Hence, higher p-xylene biodegradation rates were always initially recorded in the upper module, which resulted in a subsequent increase in temperature and a decrease in moisture content. This decrease in the moisture content in the upper module resulted in a higher removal rate in the middle module, while the moisture level in the lower module steadily increased as a result of water condensation. Based on these results, mass balance calculations performed using measured bed temperatures and relatively humidity values were successfully used to account for water balances in the biofilter over time. Finally, the absence of bed compaction after 550 days of continuous operation confirmed the suitability of this organic material for biofiltration processes. PMID- 21030150 TI - Cation exchange removal of Cd from aqueous solution by NiO. AB - Detailed adsorption experiments of Cd from aqueous solution on NiO were conducted under batch process with different concentrations of Cd, time and temperature of the suspension. The solution pH is found to play a decisive role in the metal ions precipitation, surface dissolution and adsorption of metal ions onto the NiO. Preliminary adsorption experiments show that the selectivity of NiO towards different divalent metal ions follows the trend Pb>Zn>Co>Cd, which is related to their first hydrolysis equilibrium constant. The exchange between the proton from the NiO surface and the metal from solution is responsible for the adsorption. The cation/exchange mechanism essentially remains the same for Pb, Zn, Co and Cd ions. The sorption of Cd on NiO particles is described by the modified Langmuir adsorption isotherms. The isosteric heat of adsorption (DeltaH) indicates the endothermic nature of the cation exchange process. Spectroscopic analyses provide evidence that Cd is chemisorbed onto the surface of NiO. PMID- 21030152 TI - Prevalence of Cryptosporidium baileyi in ostriches (Struthio camelus) in Zhengzhou, China. AB - Few data are available on the molecular characterization of Cryptosporidium spp. in ostriches. The objective of this study was to determine the prevalence of Cryptosporidium species or genotypes in ostriches. A total of 452 fecal samples from five farms, a zoo, and an animal rescue center in Zhengzhou, Henan Province, China were examined for Cryptosporidium oocysts by microscopy of wet mount of fecal materials concentrated by the Sheather's sugar flotation technique. Fifty three samples were Cryptosporidium-positive from four farms, with an overall prevalence of 11.7%. The percentage of animals shedding oocysts was 0, 16.2%, 7.2%, and 0 in 1-3 weeks, 4-8 weeks, 3-12 months, and more than 12 months ostriches, respectively (chi(2)=17.74; rho<0.01). PCR-restriction fragment length polymorphism (RFLP) analysis of the small subunit (SSU) rRNA gene of the 53 Cryptosporidium-positive samples showed the presence of only Cryptosporidium baileyi, which was confirmed by DNA sequencing of the SSU rRNA PCR products from 16 positive samples. Cross-transmission studies demonstrated that the C. baileyi isolate could infect chickens and quails. Thus, ostriches are commonly infected with C. baileyi that is genetically and biologically similar to C. baileyi found in other birds. PMID- 21030151 TI - Behavioral and psychosocial factors associated with insomnia in adolescents with chronic pain. AB - This study aimed to (1) identify differences in sleep behaviors, sleep quality, pre-sleep arousal and prevalence of insomnia symptoms in adolescents with chronic pain compared to a healthy age and sex-matched cohort and (2) examine pain intensity, pubertal development, depression, and pre-sleep arousal as risk factors for insomnia symptoms. Participants included 115 adolescents, 12-18 years of age (73.0% female), 59 youth with chronic pain and 56 healthy youth. During a home-based assessment, adolescents completed validated measures of pain, sleep quality, sleep hygiene, pre-sleep arousal, depressive symptoms, and pubertal development. Findings revealed a significantly higher percentage of adolescents with chronic pain reporting symptoms of insomnia (54.2%) compared to healthy adolescents (19.6%), p<.001. Youth with chronic pain also reported higher cognitive and somatic arousal at bedtime, and lower sleep quality compared to the healthy cohort. In a logistic regression, two factors emerged as significant predictors of insomnia, having chronic pain (OR=6.09) and higher levels of cognitive pre-sleep arousal (OR=1.24). Level of pain intensity did not predict insomnia. While sleep disruption may initially relate to pain, these symptoms may persist into a separate primary sleep disorder over time due to other behavioral and psychosocial factors. Assessment of insomnia may be important for identifying behavioral targets for the delivery of sleep-specific interventions to youth with chronic pain. PMID- 21030153 TI - Validation of a Leishmania infantum ELISA rapid test for serological diagnosis of Leishmania chagasi in dogs. AB - Canine visceral leishmaniasis (CVL) is caused by Leishmania donovani complex parasites including L. donovani, Leishmania infantum and Leishmania chagasi. As some studies suggest that L. chagasi and L. infantum may be very similar or even the same species, the aim of the present study was to evaluate a commercial rapid ELISA test, originally designed for L. infantum, in the diagnosis of CVL in dogs naturally infected by L. chagasi. A total of 400 serum canine samples, including 283 positive dogs for CVL from an endemic area, 86 clinically healthy dogs from a non-endemic area and 31 dogs seropositive for confounding infectious agents (Trypanosoma cruzi, Toxoplasma gondii, Neospora caninum, Babesia canis and Ehrlichia canis) were used for test validation. An overall sensitivity of 94.7% (95% CI=91.41-97.01%) and specificity of 90.6% (95% CI=83.80-95.21%) was found, with a high degree of agreement (k=0.8445) to the indirect ELISA. When confounding infectious diseases were excluded, specificity increased to 100% (95% CI=95.8-100%), with a higher degree of agreement (k=0.8928). In conclusion, the commercial kit designed for L. infantum was a highly sensitive and specific device for detection of L. chagasi infection in dogs, which indicates high immunoreactivity similarities between L. infantum and L. chagasi. PMID- 21030154 TI - Identification of Hammondia heydorni oocysts by a heminested-PCR (hnPCR-AP10) based on the H. heydorni RAPD fragment AP10. AB - Toxoplasma gondii, Hammondia hammondi, Neospora caninum, Neospora hughesi and Hammondia heydorni are members of the Toxoplasmatinae sub-family. They are closely related coccidians with similarly sized oocysts. Molecular diagnostic techniques, especially those based on polymerase chain reaction (PCR), can be successfully applied for the differentiation of Hammondia-like oocysts. In this paper, we describe a rapid and simple method for the identification of H. heydorni oocysts among other members of the Toxoplasmatinae sub-family, using a heminested-PCR (hnPCR-AP10) based on a H. heydorni RAPD fragment available in molecular database. DNA of oocysts of H. heydorni yielded a specific fragment of 289-290 bp in the heminested-PCR assay. No product was yielded when the primers were used for the amplification of DNA extracted from T. gondii, N. caninum, N. hughesi and H. hammondi, thus allowing the differentiation of H. heydorni among other members of the Toxoplasmatinae sub-family. The hnPCR-AP10 was capable of detecting H. heydorni genetic sequences from suspensions with at least 10 oocysts. In conclusion, the hnPCR-AP10 proved to be a reliable method to be used in the identification of H. heydorni oocysts from feces of dogs. PMID- 21030155 TI - Traumatic myiasis by Wohlfahrtia magnifica in Italy. AB - Seven farms, two in Central Italy and five in Southern Italy, were visited for the presence of larvae-infested wounds. Ninety-six (3%) out of 3129 sheep examined had a traumatic myiasis with a very high percentage of infested animals found only in a farm (10.5%). Wounds were mainly localized on the vulva and prepuce. Infested animals were restless, anxious, and reluctant to graze. None of the 10 goats in one infested flock had wounds, whereas a shepherd dog from another flock presented a wound on the ear. All the larvae and adults reared from them in the laboratory were identified as Wohlfahrtia magnifica (Schiner, 1862) (Diptera, Sarcophagidae). The cases presented here are the first clinical cases of wohlfahrtiosis in sheep and dogs reported in Italy, and indicate that this myiasis is endemic in this country. A wider epidemiological investigation on the prevalence, incidence and seasonality of W. magnifica infestation of Italian W. magnifica population/s would be useful to understand its geographical provenience and the likely risk for its spreading throughout Italy and other non-endemic areas. PMID- 21030156 TI - Tranilast could has potential therapeutic value in the treatment of psoriasis. AB - Psoriasis is a common chronic skin disease characterized by recurrent erythromatous skin plaques that exhibit epidermal hyperplasia, variable inflammatory cell infiltrate, and abnormalities of the dermal vascularization. The involvement of angiogenic growth factors such as vascular endothelial growth factor (VEGF), matrix metalloproteinases (MMPs) and inflammatory cytokines such as IFNgamma, IL-1, IL-2, TNFalpha, TGFalpha and beta, IL-6, IL-8, amphiregulin and monocyte chemoattractant protein 1 (MCP-1) have been known to play pathogenic roles in traumatic psoriatic skin. However, anti-angiogenic and anti-inflammatory cytokines regimens might favorably affect the psoriasis disease process. Tranilast is an anti-allergic drug now emerging as anti-angiogenesis and anti inflammatory effects. In vitro and in vivo experiments have also been strongly showed that tranilast would treat skin psoriasis by inhibition of involving factors. Herein, we hypothesize that local administration of tranilast may be potentially clinically useful in psoriasis. PMID- 21030157 TI - The efficacy of radiation therapy in the treatment of Graves' orbitopathy. AB - PURPOSE: To review our institutional outcomes of patients treated with radiation therapy (RT) for Graves' orbitopathy (GO), assess the role of orbital reirradiation, and identify prognostic factors of complete response (CR). METHODS AND MATERIALS: This is a retrospective review of 211 patients who presented with a diagnosis of GO and received RT between January 2000-2010. RT dose was 20 Gy in 10 fractions. Patient median age was 51 years (range, 15-84 years), median follow up was 11 months (range, 1-88 months). Patient symptoms included any combination of proptosis (90.9%), extraocular muscle dysfunction (78.9%), soft tissue signs (68.4%), and diplopia (58.4%). Corticosteroids were used as first-line therapy in 20.6% of patients. Among those who achieved either CR or partial response (PR), prognostic factors were evaluated. RESULTS: Stabilization of disease without recurrence was clinically achieved overall in 202 patients (96.7%). At the completion of RT, 176 patients (84.2%) reported a symptomatic improvement of pretreatment symptoms. CR of GO symptoms was achieved using multiple treatment modalities, including RT by 93 patients (44.5%), of which 32 patients received RT only. Corticosteroids were discontinued in 97.8% of patients who received them as initial therapy. Surgical intervention following radiotherapy was required for 144 (68.9%) of all patients. Fourteen patients received orbital reirradiation for persistent or recurrent symptoms. Five of these achieved a CR, and the other nine achieved disease stabilization but retained persistent ocular symptoms. Long-term side effects of RT included dry eyes (12%). Of the prognostic factors we investigated, only gender predicted CR, which was less common in men (33.9%) than in women (49.7%) p = 0.0471. CONCLUSIONS: Orbital radiation for GO is an established treatment modality for patients. Orbital reirradiation is beneficial for patients who do not respond to initial RT or experience symptom recurrence without an apparent risk of increased morbidity. PMID- 21030158 TI - Longitudinal study of intestinal symptoms and fecal continence in patients with conformal radiotherapy for prostate cancer. AB - PURPOSE: To prospectively assess the intestinal symptoms and fecal continence in patients who had undergone conformal radiotherapy (CRT) for prostate cancer. METHODS AND MATERIALS: A total of 78 men who had undergone definitive CRT for prostate cancer were evaluated. The patients were assessed before, during (treatment Weeks 4 and 6), and 2, 12, and 24 months after CRT completion. The intestinal symptoms and fecal continence were evaluated with comprehensive standardized questionnaires. RESULTS: The intestinal symptoms were mostly intermittent, with only a small minority of patients affected daily. Defecation pain, fecal urge, and rectal mucous discharge increased significantly during therapy. Defecation pain and rectal mucous discharge had returned to baseline levels within 8 weeks and 1 year after CRT, respectively. However, fecal urge remained significantly elevated for <=1 year and then returned toward the pretreatment values. The prevalence of rectal bleeding was significantly elevated 2 years after CRT. Fecal continence deteriorated during CRT and remained impaired at 1 year after treatment. Incontinence was mostly minor, occurring less than once per week and predominantly affecting incontinence for gas. CONCLUSION: Intestinal symptoms and fecal incontinence increased during prostate CRT. Except for rectal bleeding, the intestinal symptoms, including fecal incontinence, returned to baseline levels within 1-2 years after CRT. Thus, the rate of long term late radiation-related intestinal toxicity was low. PMID- 21030159 TI - Rates of second malignancies after definitive local treatment for ductal carcinoma in situ of the breast. AB - PURPOSE: We analyzed the risk of second malignancies developing in patients with ductal carcinoma in situ (DCIS) undergoing surgery and radiotherapy (S+RT) vs. surgery alone. METHODS AND MATERIALS: The S+RT cohort consisted of 256 women treated with breast-conserving therapy at William Beaumont Hospital. The surgery alone cohort consisted of 2,788 women with DCIS in the regional Surveillance, Epidemiology, and End Results database treated during the same time period. A matched-pair analysis was performed in which each S+RT patient was randomly matched with 8 surgery alone patients (total of 2,048 patients). Matching criteria included age+/-2 years. The rates of second malignancies were analyzed overall and as contralateral breast vs. non-breast cancers and by organ system. RESULTS: Median follow-up was 13.7 years for the S+RT cohort and 13.3 years for the surgery alone cohort. The overall 10-/15-year rates of second malignancies among the S+RT and surgery alone cohorts were 14.2%/24.2% and 16.4%/22.6%, respectively (p=0.668). The 15-year second contralateral breast cancer rate was 14.2% in the S+RT cohort and 10.3% in the surgery alone cohort (p=0.439). The 15 year risk of a second non-breast malignancy was 14.2% for the S+RT cohort and 13.4% for the surgery alone cohort (p=0.660). When analyzed by organ system, the 10- and 15-year rates of second malignancies did not differ between the S+RT and surgery alone cohorts for pulmonary, gastrointestinal, central nervous system, gynecologic, genitourinary, lymphoid, sarcomatoid, head and neck, or unknown primary tumors. CONCLUSIONS: Compared with surgery alone, S+RT is not associated with an overall increased risk of second malignancies in women with DCIS. PMID- 21030160 TI - FDG-PET assessment of the effect of head and neck radiotherapy on parotid gland glucose metabolism. AB - PURPOSE: Functional imaging with [F-18]-fluorodeoxyglucose positron emission tomography (FDG-PET) provides the opportunity to define the physiology of the major salivary glands before and after radiation therapy. The goal of this retrospective study was to identify the radiation dose-response relationship of parotid gland glucose metabolism in patients with head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: Forty-nine adults with HNSCC were identified who had curative intent intensity-modulated radiation therapy (IMRT) and FDG-PET imaging before and after treatment. Using a graphical user interface, contours were delineated for the parotid glands on axial CT slices while all authors were blinded to paired PET slices. Average and maximal standard uptake values (SUV) were measured within these anatomic regions. Changes in SUV and volume after radiation therapy were correlated with parotid gland dose-volume histograms from IMRT plans. RESULTS: The average parotid gland volume was 30.7 mL and contracted 3.9 +/- 1.9% with every increase of 10 Gy in mean dose (p = 0.04). However, within the first 3 months after treatment, there was a uniform reduction of 16.5% +/- 7.3% regardless of dose. The average SUV(mean) of the glands was 1.63 +/- 0.48 pretreatment and declined by 5.2% +/- 2.5% for every increase of 10 Gy in mean dose (p = 0.04). The average SUV(max) was 4.07 +/- 2.85 pretreatment and decreased in a sigmoid manner with mean dose. A threshold of 32 Gy for mean dose existed, after which SUV(max) declined rapidly. CONCLUSION: Radiation dose responses of the parotid glands can be measured by integrated CT/FDG-PET scans. Retrospective analysis showed sigmoidal declines in the maximum metabolism but linear declines in the average metabolism of the glands with dose. Future studies should correlate this decline in FDG uptake with saliva production to improve treatment planning. PMID- 21030161 TI - Is elective irradiation to the lower neck necessary for N0 nasopharyngeal carcinoma?: in regard to Macmillan MS et al. (Int J Radiat Oncol Biol Phys 2010;77:1397-1402). PMID- 21030162 TI - Irradiation and bevacizumab in high-grade glioma retreatment settings. AB - PURPOSE: Reirradiation is a treatment option for recurrent high-grade glioma with proven but limited effectiveness. Therapies directed against vascular endothelial growth factor have been shown to exert certain efficacy in combination with chemotherapy and have been safely tested in combination with radiotherapy in a small cohort of patients. To study the feasibility of reirradiation combined with bevacizumab treatment, the toxicity and treatment outcomes of this approach were analyzed retrospectively. PATIENTS AND METHODS: After previous treatment with standard radiotherapy (with or without temozolomide) patients with recurrent malignant glioma received bevacizumab (10 mg/kg intravenous) on Day 1 and Day 15 during radiotherapy. Maintenance therapy was selected based on individual considerations, and mainly bevacizumab-containing regimens were chosen. Patients received 36 Gy in 18 fractions. RESULTS: The data of the medical charts of the 30 patients were analyzed retrospectively. All were irradiated in a single institution and received either bevacizumab (n = 20), no additional substance (n = 7), or temozolomide (n = 3). Reirradiation was tolerated well, regardless of the added drug. In 1 patient treated with bevacizumab, a wound dehiscence occurred. Overall survival was significantly better in patients receiving bevacizumab (p = 0.03, log-rank test). In a multivariate proportional hazards Cox model, bevacizumab, Karnovsky performance status, and World Health Organization grade at relapse turned out to be the most important predictors for overall survival. CONCLUSION: Reirradiation with bevacizumab is a feasible and effective treatment for patients with recurrent high-grade gliomas. A randomized trial is warranted to finally answer the question whether bevacizumab adds substantial benefit to a radiotherapeutic retreatment setting. PMID- 21030163 TI - [Postoperative morbidity after completion surgery following homogeneous chemoradiation therapy in locally advanced cervical cancer]. AB - OBJECTIVE: To evaluate the morbidity rate in patients following completion surgery (hysterectomy+/-lymphadenectomy) after chemoradiation therapy (CRT) for an advanced stage cervical cancer. PATIENTS AND METHODS: Patients fulfilling the following inclusion criteria were studied: (1) stage IB2-IVA cervical carcinoma; (2) tumor initially confined to the pelvic cavity; (3) pelvic external radiation therapy with delivery of 45Gy with concomitant chemotherapy (cisplatin 40mg/m(2)/week) followed by utero-vaginal brachytherapy; (4) completion surgery after the end of radiation therapy including at least a hysterectomy. RESULTS: One-hundred and fifty patients treated between 1998 and 2007 fulfilled inclusion criteria. Thirty-seven (25%) patients had 55 post-operative complications (17 had severe complications requiring surgical or radiological treatment). Two deaths related to postoperative morbidity had occurred. The risk of complications was increased with a radical hysterectomy (OR=2.4; P=0.04) and the presence of residual cervical disease (<=1cm: OR=4.3, >1cm: OR=2.5; P=0.01). CONCLUSION: In the present study, the morbidity of completion surgery (based on hysterectomy with or without lymphadenectomy) is very high in patients treated with initial CRT for locally advanced cervical cancer whereas the therapeutic value of such surgery remains unproven. PMID- 21030164 TI - Population screening of risky alcohol and drug use via Internet and Interactive Voice Response (IVR): a feasibility and psychometric study in a random sample. AB - BACKGROUND: The wide accessibility of computer-based technologies like the Internet and Interactive Voice Response (IVR) systems raises the question of whether population survey data could be collected more easily and cheaply compared to using paper questionnaires. In the area of possibly stigmatized behaviors such as problematic alcohol and drug use, the question extends to whether the prevalence of such behaviors in the general population could be surveyed without compromising the quality of the data. AIMS: This study compares Internet and IVR versions of the AUDIT and DUDIT with respect to: (1) response rate, (2) problematic alcohol and drug use and (3) reliability. METHOD: 5000 individuals, randomly selected from the Swedish general population, were contacted via postal mail and invited to complete the AUDIT and DUDIT questionnaires via Internet or IVR. In total, 1861 (37.8%) participated in the study, 1089 via Internet and 772 via IVR. RESULTS: The Internet administration mode yielded a higher response rate (38.1%) compared to the IVR mode (33.9%). When respondents were given a choice between Internet and IVR, a higher response rate resulted (43.2-46.6%). Problematic alcohol and drug use occurred among 21.1% and 2.8% of the sample, respectively, with no significant differences by administration mode. Both the AUDIT and DUDIT exhibited satisfactory reliability across administration modes, Cronbach's alpha 0.76/0.86. CONCLUSIONS: Data quality does not deteriorate with computerized administration methods for the AUDIT and DUDIT in population studies but paper questionnaires should also be made available to respondents in order to maximize response rates. PMID- 21030165 TI - Purification and characterization of the subtilisin-like protease of Streptococcus suis that contributes to its virulence. AB - Streptococcus suis is a major swine pathogen that is responsible for severe infections such as meningitis, endocarditis, and septicemia. S. suis is also recognized as a zoonotic agent and expresses several virulence factors. The recently identified subtilisin-like protease (SspA) of S. suis plays an important role in the pathogenicity of this bacterium in animal models. The objective of the present study was to clone, purify, and characterize the SspA of serotype 2 S. suis P1/7. The SSU0757 gene encoding SspA was amplified and a 4798-bp DNA fragment was obtained. It was cloned into the expression plasmid pBAD/HisB and then inserted into Escherichia coli to overproduce the protein. The recombinant protease was purified by chromatography procedures and showed a molecular weight of 170 kDa by SDS-PAGE. Its activity was optimal at pH 7 and at temperatures ranging from 25 degrees C to 37 degrees C. It had a high specificity for the chromogenic substrate succinyl-Ala-Ala-Pro-Phe-pNa while specific inhibitors of serine proteases inhibited its activity. In addition to degrading gelatin, the protease hydrolyzed the Aalpha chain of fibrinogen, which prevented fibrin formation by thrombin. The recombinant subtilisin-like protease also showed toxicity towards brain microvascular endothelial cells. Lastly, sera from pigs infected with S. suis reacted with the recombinant SspA, indicating that it is produced during infections. In conclusion, the SspA of S. suis shared similarities with subtilisin-like proteases produced by other pathogenic streptococci and may contribute to the pathogenic process of S. suis infections. PMID- 21030166 TI - Gender and medical careers. AB - The concerns about physicians' career advancement tend to be raised in gender terms, because women presently constitute close to and will soon form a majority of the medical students in most western societies. The question is to what extent female and male medical students and residents today make similar or different career and lifestyle choices? Two major mechanisms have been referred to as the reason for gender differences in career paths for physicians. The major theoretical framework tends to be the socialization or sex-role theory and later versions of this explanatory framework. The other mechanism referred to is structural and points to the barriers or the concrete support that women and men experience in making their career decisions. Studies of medical students in the UK and US have shown that women students expected family demands to hamper career plans, while male students were less influenced by family concerns. The importance of role models and mentors in setting the career goals of medical students and residents has recently confirmed early studies of the topic. A number of studies have documented that early negative experiences or lack of encouragement in medical school deter women from choosing surgery as a career. Recent studies suggest that lifestyle choices rather than merely career advancement influence both female and male surgeons' career plans. PMID- 21030167 TI - Comparison of injuries sustained by drivers and pillion passengers in fatal head on motorcycle collision accidents. AB - This study aimed to compare injuries sustained by motorcycle drivers with those sustained by pillion passengers in fatal head-on motorcycle collision accidents. We examined 84 cases of fatal head-on motorcycle collision accidents, causing 79 deaths of drivers and 19 deaths of pillion passengers, using medical and medico legal examination records. The distribution of superficial injuries, characteristic injuries, injury severity as well as fatal causes was evaluated and compared using chi(2) tests. The results revealed a significant difference in the distribution of superficial injuries between drivers and passengers. The proportions of injuries in the hand and perineum regions were significantly higher in drivers than passengers. Some characteristic superficial injuries on the palms, chest, abdomen as well as the perineum areas were observed in drivers, while none of these characteristic injuries were observed in pillion passengers. Drivers were found to have suffered more severe chest and abdomen injuries than passengers. In addition, there was a higher incidence of fatalities involving run over injuries for drivers compared with pillion passengers. The proportion of fatal injuries related to tumbling was higher for passengers than for drivers. Overall, our results revealed a difference in injury severity, superficial injury distribution and characteristic injuries between drivers and passengers. Few characteristic injuries were found in pillion passengers. These findings could help to guide medico-legal examinations, particularly in identifying drivers among victims involved in traffic accidents. PMID- 21030168 TI - Sinonasal inhalation of dornase alfa in CF: A double-blind placebo-controlled cross-over pilot trial. AB - OBJECTIVE: The paranasal sinuses are almost always involved in cystic fibrosis, and chronic rhinosinusitis and nasal polyps are very frequent in the disease. Hereby, the patients' quality of life and their overall health are relevantly impaired. Although dornase alfa, a mucolytic agent, may also be effective in the upper airways, deposition of inhaled drugs into paranasal sinuses is substantially limited. The novel PARI SINUSTM nebuliser has been shown in deposition studies to deliver aerosol into paranasal sinuses but has not yet been clinically tested. This DBPC pilot-trial applying dornase alfa aims to evaluate outcome parameters and sample sizes for a subsequent efficacy trial. METHODS: Primary outcome parameters assessed were the Sino-Nasal Outcome Test (SNOT-20, a disease-specific quality of life assessment tool) and ventilated volume as measured by magnetic resonance imaging. Five CF patients were randomised to inhale either dornase alfa or 0.9% NaCl for 28 days and, after a wash-out period of 28 days, crossed over to the alternative treatment. RESULTS: Whereas normal saline was not associated with relevant changes in SNOT-20 scores, dornase alfa improved quality of life (p=0.043). MRI results showed no definite trend. CONCLUSION: This first clinical study with the novel device gives promising results for the new therapeutic concept of sinonasal inhalation with vibrating aerosols in regard to further analysis involving larger collectives. PMID- 21030169 TI - Influence of liquid crystal displays (LCDs) with different resolutions on the detection of pulmonary nodules: an observer performance study. AB - PURPOSE: To evaluate the influence of monochrome LCDs with different resolutions on the detection performance of pulmonary nodules. MATERIALS AND METHODS: 187 chest DR images were selected from our hospital's picture archiving and communication system (PACS), including 111 normal cases and 76 cases with solitary pulmonary nodules. Those positive images were divided into two groups, A and B, according to the diameter of nodules. Three high-, three mid-, and three low-experienced radiologists interpreted those images with a 2 megapixel (MP), a 3 MP and a 5 MP monochrome LCD independently. Regarding the presence of the nodule, five-point confidence level rating scale was used: definite absence, probable absence, indetermination, probable presence and definite presence. The observers were requested to rank each image on the given display according to the presence of pulmonary nodule. Receiver operation characteristic (ROC) analysis was used to interpret the data. RESULTS: When detecting the pulmonary nodules of Group A on 2 MP-, 3 MP- and 5 MP-LCD, the areas under ROC curves (AUCs) were 0.641, 0.683 and 0.732 for high-experienced radiologists, 0.633, 0.679 and 0.716 for mid-experienced radiologists, 0.620, 0.652 and 0.719 for low-experienced radiologists, respectively; when detecting the pulmonary nodules of Group B, the AUCs were 0.811, 0.830 and 0.842 for high-experienced radiologists, 0.771, 0.821 and 0.837 for mid-experienced radiologists, 0.759, 0.770 and 0.829 for low experienced radiologists, respectively. However, there were no significant differences among different reading modalities. CONCLUSION: For detecting pulmonary nodules, it is equivalent of observer performance among 2 MP-, 3 MP- and 5 MP-LCD. PMID- 21030170 TI - Differentiation between ductal carcinoma in situ and mastopathy using dynamic contrast-enhanced magnetic resonance imaging and a model of contrast enhancement. AB - The purpose of this study was to retrospectively evaluate the feasibility of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to differentiate between ductal carcinoma in situ (DCIS) and mastopathy by analyzing their time intensity curves (TICs) using the two-compartment pharmacokinetic model with an assumption of instantaneous injection of contrast medium (TCPM). After the pre contrast MRI was performed using a 1.5 T MRI system, DCE-MRI was performed four times after the intravenous administration of contrast medium. We set the volumes of interest (VOIs) on the tumor and normal mammary gland, and obtained the TICs in these VOIs. We calculated the following parameters by fitting these TICs to the equation derived from TCPM; the initial slope of the TIC (Slopeini), the area under the TIC (AUC), the time to peak enhancement (TTP) and the peak enhancement (PeakE). We calculated these parameters in both the lesion and normal mammary gland and the ratios of the parameters in the lesion to those in the normal gland (rSlopeini, rAUC, rTTP and rPeakE). There were significant differences in Slopeini (P=0.009), PeakE (P=0.019), rSlopeini (P=0.010), and rTTP (P=0.005) between DCIS and mastopathy. The areas under the receiver operating characteristic curve for Slopeini, PeakE, rSlopeini, and rTTP were 0.67+/-0.06 (P=0.009), 0.65+/-0.06 (P=0.019), 0.67+/-0.06 (P=0.01), and 0.68+/-0.06 (P=0.005), respectively. In conclusion, our results suggest that analysis of TICs obtained by DCE-MRI using TCPM appears to be useful for differentiating between DCIS and mastopathy. PMID- 21030171 TI - Triggered non-contrast enhanced MR angiography of peripheral arteries: optimization of systolic and diastolic time delays for electrocardiographic triggering. AB - The purpose of this study was to determine the optimal systolic and diastolic time delays for electrocardiographic triggering of a non-contrast media enhanced MR angiography using a 3-dimensional fast spin echo sequence in patients suffering from peripheral arterial disease. 12 patients with suspected peripheral arterial disease were examined on a 1.5 T Philips Achieva MR scanner. A cardiac triggered Volumetric Isotropic T2-weighted fast spin echo sequence was performed using variable trigger delays for systolic and diastolic phase. The signal in the popliteal arteries and anterior tibial arteries of the systolic and diastolic images was measured and optimal delay times for systolic and diastolic phase were determined. Minimum signal to noise ratio (SNR) appears at the time difference DeltaT=-21 ms on systolic images of the popliteal arteries. In the anterior tibial arteries the minimum SNR is significantly higher and appears at the time difference DeltaT=-14 ms. Diastolic delay times must be chosen as long or as short as possible depending on heart rate. In peripheral vessels triggered non contrast MR angiography can yield results which are comparable with contrast enhanced MRA techniques. It is crucial to optimize timing parameters. PMID- 21030172 TI - CT-guided cutting needle biopsy of lung lesions--an effective procedure for adequate material and specific diagnose. AB - OBJECTIVE: Computed guided percutaneous biopsy of lung lesions is widely accepted as an effective and safe procedure for specific diagnose. The purpose of this study is to present the experience of an oncology center in the use of computed tomography (CT)-guided cutting needle biopsy as an effective procedure for adequate material and specific diagnose of lung lesions. SUBJECTS AND METHODS: This study reports a retrospective analysis of 94 consecutive patients admitted in an oncologic center, reference in Brazil (Hospital do Cancer-AC Camargo), between 1996 and 2004, who were submitted to 97 CT guided cutting needle biopsy of pulmonary lesions. Informations of material adequacy and specific diagnose were studied. RESULTS: In a total of 97 biopsies of lung lesions, 94 (96.9%) supplied adequate material for histological analyses with 71 (73.2%) as malignant lesions and 23 (23.7%) diagnosed as benign lesions and in 3 biopsies the material supplied was inadequate. The frequency of specific diagnosis was higher in both malignant and benign lesions with 63 (88.7%) cases and 20 (86.7%) cases respectively. CONCLUSIONS: CT-guided cutting needle biopsy is an effective procedure for adequate material and specific diagnostic for malignant and benign lung lesions. PMID- 21030173 TI - Kimura's disease: the CT and MRI characteristics in fifteen cases. AB - OBJECTIVE: To summarize the CT and MRI features in a series of fifteen cases of Kimura's disease. MATERIALS AND METHODS: The clinical data, CT and MRI findings of 15 patients with histologically proved Kimura's disease were retrospectively reviewed. All imaging data were consensually evaluated by two radiologists to determine the lesion location, number, morphology, margin, signal intensity or CT density, lesion texture, contrast enhancement pattern and involvement of adjacent structures. RESULTS: There were 14 male and 1 female, with peripheral blood eosinophilia in all 14 patients. 13 patients were presented with a painless mass. 13 patients had lesions located in the head and neck related to the major salivary glands. 1 patient had lesion in groin. Subcutaneous fat diffuse atrophy around the tumor site was found in 11 patients. 9 patients had solitary mass and 6 patients had multiple masses. Most masses were ill-defined, but no specific density or signal patterns were found. Most patients exhibited enlarged or obviously enhanced abnormal lymph nodes but without necrosis. CONCLUSION: The characteristic distribution, morphology with enlarged draining lymphadenopathy, combined with the clinical features and laboratory examination enables a confident preoperative diagnosis of Kimura's disease. PMID- 21030174 TI - Value of "protruding lips" sign in malignant bowel obstructions. AB - OBJECTIVE: This study aims to evaluate the diagnostic accuracy of a new CT sign in order to define or exclude a malignant aetiology of bowel obstruction. MATERIALS AND METHODS: CT scans of 137 patients affected by bowel obstruction were reviewed. Colonic obstruction occurred in 47 (34%) cases, small bowel obstruction in 90 (66%). Neoplastic aetiology was found in 42 cases (31%), while in the remaining 95 (69%) obstruction was caused by non-neoplastic conditions. Definitive diagnosis was surgically confirmed in all patients. CT images were evaluated searching for bowel obstruction's signs and for the presence of the "protruding lips" sign on the proximal surface of stenosis, which is represented by the evidence of a protrusion within the dilated loop. RESULTS: The sign was found in 31 (23%) cases, all of neoplastic origin. When malignant obstruction was diagnosed, sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy values of the described sign were 74%, 100%, 100%, 90% and 92%, respectively. CONCLUSIONS: The "protruding lips" sign represents an alteration to be searched when bowel obstruction is diagnosed by CT examination. Its evidence correlates to a malignant condition with a 100% probability and when it is not found, the probability of a non-neoplastic condition is 90%. PMID- 21030175 TI - Comparison of the manual and computer-aided techniques for evaluation of wrist synovitis using dynamic contrast-enhanced MRI on a dedicated scanner. AB - OBJECTIVE: Traditional methods for assessment of synovial inflammation in rheumatoid arthritis such as clinical examination, immunohistology of bioptic samples, scintigraphy, and radiography have several limitations, including lack of sensitivity, need of invasive techniques, and administration of radioactive material. MRI lacks on standardisation and the data are often analysed using laborious, relatively rigid scoring methods. MATERIALS AND METHODS: This study introduces a standardized computer-aided method for quantitative analysis of MRI of the wrist on a dedicated scanner. Assessment of the synovial inflammation was performed using a semi-automated model-based method in conjunction with patient motion reduction algorithms. Further, the new method was compared with the traditional user-dependent ROI-based technique. RESULTS: The computer-aided technique generated robust and reproducible results. Application of motion reduction algorithms allowed for significant improvements of the signal to noise ratio, which is especially important in the datasets acquired with low-field scanners. CONCLUSION: The use of the computer software can be beneficial for diagnostic decision in cross sectional as well as longitudinal MRI examinations of the wrist in rheumatoid arthritis. PMID- 21030176 TI - Transarterial Onyx packing of the transverse-sigmoid sinus for dural arteriovenous fistulas. AB - OBJECTIVE: To report transarterial Onyx packing of the transverse-sigmoid sinus for dural arteriovenous fistulae (DAVFs). METHODS: We retrospectively studied consecutive 5 patients (2 female and 3 male) treated for a transverse-sigmoid sinus DAVF since 2008 in whom transverse sinus packing was attempted with a transarterial approach Onyx embolization. The mean clinical follow-up period was 6.2 months. RESULTS: Of the five lesions, 2 fistulas were type IIa, 3 were type IIb, according to the Cognard classification. Five Onyx embolizations were all performed via the middle meningeal artery. Cure was obtained in all cases after completion of direct sinus packing. No complications were revealed. CONCLUSIONS: Transarterial Onyx packing of transverse-sigmoid sinus for DAVFs via the meningeal arterial system is a safe therapeutic alternative in selected cases. PMID- 21030177 TI - High-resolution CT for identify patients with smear-positive, active pulmonary tuberculosis. AB - PURPOSE: This study evaluates the use of high-resolution computed tomography (HRCT) to differentiate smear-positive, active pulmonary tuberculosis (PTB) from other pulmonary infections in the emergency room (ER) setting. METHODS: One hundred and eighty-three patients diagnosed with pulmonary infections in an ER were divided into an acid fast bacillus (AFB) smear-positive, active PTB group (G1=84) and a non-AFB smear-positive, pulmonary infection group (G2=99). HRCT images from a 64-Multidetector CT were analyzed, retrospectively, for the morphology, number, and segmental distribution of pulmonary lesions. RESULTS: Utilizing multivariate analysis, five variables were found to be independent risk factors predictive of G1: (1) consolidation involving the apex segment of right upper lobe, posterior segment of the right upper lobe, or apico-posterior segment of the left upper lobe; (2) consolidation involving the superior segment of the right or left lower lobe; (3) presence of a cavitary lesion; (4) presence of clusters of nodules; (5) absence of centrilobular nodules. A G1 prediction score was generated based on these 5 criteria to help differentiate G1 from G2. The area under the receiver operating characteristic (ROC) curve was 0.96 +/- 0.012 in our prediction model. With an ideal cut-off point score of 3, the specificity, sensitivity, positive predictive value (PPV), and negative predictive value (NPV) are 90.9%, 96.4%, 90.0% and 96.8%, respectively. CONCLUSION: The use of this AFB smear-positive, active PTB prediction model based on 5 key HRCT findings may help ER physicians determine whether or not isolation is required while awaiting serial sputum smear results in high risk patients. PMID- 21030178 TI - Use of dynamic contrast-enhanced MRI to measure subtle blood-brain barrier abnormalities. AB - There is growing interest in investigating the role of subtle changes in blood brain barrier (BBB) function in common neurological disorders and the possible use of imaging techniques to assess these abnormalities. Some studies have used dynamic contrast-enhanced MR imaging (DCE-MRI) and these have demonstrated much smaller signal changes than obtained from more traditional applications of the technique, such as in intracranial tumors and multiple sclerosis. In this work, preliminary results are presented from a DCE-MRI study of patients with mild stroke classified according to the extent of visible underlying white matter abnormalities. These data are used to estimate typical signal enhancement profiles in different tissue types and by degrees of white matter abnormality. The effect of scanner noise, drift and different intrinsic tissue properties on signal enhancement data is also investigated and the likely implications for interpreting the enhancement profiles are discussed. No significant differences in average signal enhancement or contrast agent concentration were observed between patients with different degrees of white matter abnormality, although there was a trend towards greater signal enhancement with more abnormal white matter. Furthermore, the results suggest that many of the factors considered introduce uncertainty of a similar magnitude to expected effect sizes, making it unclear whether differences in signal enhancement are truly reflective of an underlying BBB abnormality or due to an unrelated effect. As the ultimate aim is to achieve a reliable quantification of BBB function in subtle disorders, this study highlights the factors which may influence signal enhancement and suggests that further work is required to address the challenging problems of quantifying contrast agent concentration in healthy and diseased living human tissue and of establishing a suitable model to enable quantification of relevant physiological parameters. Meanwhile, it is essential that future studies use an appropriate control group to minimize these influences. PMID- 21030179 TI - Quantitative assay for bradykinin in rat plasma by liquid chromatography coupled to tandem mass spectrometry. AB - An assay to quantify bradykinin in rat plasma has been developed and validated, using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). Sar-D Phe(8)-des-Arg(9)-bradykinin was used as internal standard. Aprotinin was added to rat plasma to inhibit the activity of proteinases. Recoveries for solid-phase extraction (SPE) on Strata X reversed phase were greater than 80%. Multiple reaction monitoring (MRM) on a triple quadrupole mass spectrometer equipped with an electrospray source (ESI), operating in the positive ion-mode, was used for detection. The assay was validated and stability was explored. Bradykinin (10-500 ng/mL) was quantified with accuracy values (% RE) below 10% and intra- and inter day precisions (% RSD) below 12 and 16%, respectively, for all concentrations. The method was successfully applied to several plasma samples from low levels kallikrein rats (LKRs) compared with normal kallikrein rats (NKRs). PMID- 21030180 TI - Successful therapeutic hypothermia in a cardiac arrest patient with profound thrombocytopenia: a case report and literature review. PMID- 21030182 TI - Continuous neostigmine infusion versus bolus neostigmine in refractory Ogilvie syndrome. PMID- 21030181 TI - The impact of emergency medical services on the ED care of severe sepsis. AB - OBJECTIVE: The identification and treatment of critical illness is often initiated by emergency medical services (EMS) providers. We hypothesized that emergency department (ED) patients with severe sepsis who received EMS care had more rapid recognition and treatment compared to non-EMS patients. METHODS: This was a prospective observational study of ED patients with severe sepsis treated with early goal-directed therapy (EGDT).We included adults with suspected infection, evidence of systemic inflammation, and either hypotension after a fluid bolus or elevated lactate. Prehospital and ED clinical variables and outcomes data were collected. The primary outcome was time to initiation of antibiotics in the ED. RESULTS: There were 311 patients, with 160 (51.4%) transported by EMS. Emergency medical services-transported patients had more organ failure (Sequential Organ Failure Assessment score, 7.0 vs 6.1; P = .02), shorter time to first antibiotics (111 vs 146 minutes, P = .001), and shorter time from triage to EGDT initiation (119 vs 160 minutes, P = .005) compared to non-EMS-transported patients. Among EMS patients, if the EMS provider indicated a written impression of sepsis, there was a shorter time to antibiotics (70 vs 122 minutes, P = .003) and a shorter time to EGDT initiation (69 vs 131 minutes, P = .001) compared to those without an impression of sepsis. CONCLUSIONS: In this prospective cohort, EMS provided initial care for half of the patients with severe sepsis requiring EGDT. Patients presented by EMS had more organ failure and a shorter time to both antibiotic and EGDT initiation in the ED. PMID- 21030183 TI - Febrile neutropenia in EDs: the role of an electronic clinical practice guideline. AB - PURPOSE: Evidence-based clinical practice guidelines (CPGs) for managing febrile neutropenia (FN) are widely available; however, the integration of guidelines into routine practice is often incomplete. This study evaluated the uptake and clinical impact of implementing an electronic CPG on the management and outcomes of patients presenting with FN at 4 urban emergency departments (ED). METHODS: A retrospective chart review over a 3-year period at 4 hospitals in Edmonton, Alberta, was performed. Potentially eligible patient visits were identified by searching the Ambulatory Care Classification System database using International Classification of Diseases, 10th Edition, codes and ED physician diagnoses of FN. ED patients with fever (>38 degrees C at home or in ED) and neutropenia (white blood cell count of <1000 cells/mm(3) or a neutrophil count of <500 cells/mm(3)) who received an ED diagnosis of FN were included. RESULTS: From 371 potential cases, 201 unique cases of FN were included. Overall, the electronic CPG was used in 76 (37.8%) of 201 patient visits; however, there were significant differences in CPG utilization between hospitals. Clinical practice guideline usage was greatest at the University of Alberta Hospital (57%). This finding correlated with a decrease in time from triage to first antibiotic by 1 hour compared to the 3 control hospitals (3.9 vs 4.9 hours, P = .022). CONCLUSIONS: The electronic CPG is a useful clinical tool that can improve patient management in the ED, and strategies to increase its utilization in this and other regions should be pursued. PMID- 21030184 TI - Beating the odds--surviving extreme hyperkalemia. AB - Severe hyperkalemia (>7 mmol/L) is a medical emergency because of possible fatal arrhythmias. We here report the case of a 58-year-old woman surviving extreme hyperkalemia (>10 mmol/L). The patient with a history of congestive heart failure, a DDD pacemaker and mild chronic renal insufficiency was admitted with progressive weakness and sudden onset of hypotension and bradycardia in the absence of any pacemaker action. Laboratory tests revealed an extreme serum potassium level of 10.1 mmol/L, with a slightly elevated serum creatinine of 149 MUmol/L. Treatment with norepinephrine, sodium bicarbonate, and insulin improved both the hemodynamic situation and the serum potassium with subsequent regaining pacemaker actions even before additional hemodialysis normalized the potassium level. A thorough investigation demonstrated that several mechanisms contributed to the extreme potassium level: urinalysis and a low transtubular potassium gradient in the presence of metabolic acidosis with normal anion gap pointed to preexisting interstitial nephritis, with renal tubular acidosis type IV as the predisposing factor, whereas several drugs and acute impairment of renal function contributed to the dangerous situation. Despite the odds for fatal outcome, the patient recovered completely, and long-term management was initiated to prevent recurrent hyperkalemia. PMID- 21030185 TI - Occult pneumothorax on chest X-ray. PMID- 21030186 TI - Massive digestive tract bleeding due to pancreatic pseudocyst: a case report. PMID- 21030187 TI - Comments on tracheal intubation using Macintosh and video laryngoscopes during chest compressions. PMID- 21030188 TI - Recombinant tissue plasminogen activator for both pulmonary and cerebral embolism. PMID- 21030189 TI - Hemodynamic changes as a diagnostic tool in acute heart failure--a pilot study. AB - OBJECTIVES: To examine whether posturally induced changes in cardiac output differentiate patients presenting with dyspnea to the emergency department (ED) with acute heart failure (AHF) from other causes. METHODS: This was an observational study of patients presenting to the ED with dyspnea. Exclusion criteria included ischemic chest pain, electrocardiographic changes diagnostic of acute myocardial infarction, pericardial effusion or chest wall deformities causing dyspnea, or heart transplant. Hemodynamic variables of cardiac index (CI), total peripheral resistance index, and thoracic fluid content (TFC) were determined in upright seated and supine positions 3 minutes apart using bioreactance technology (Cheetah Medical Inc, Portland, Ore). Acute heart failure was defined as either B-type natriuretic peptide 100 to 500 pg/mL and discharge diagnosis of AHF or a B-type natriuretic peptide greater than 500 pg/mL. RESULTS: Of 92 patients, 25 had AHF, 23 had asthma/chronic obstructive pulmonary disease (COPD), and 44 had dyspnea related to other conditions; 41 (44.1%) were male, 56 (60.2%) were African American, and the mean age was 58 +/- 15.0 years. Mean baseline TFC was higher in AHF vs asthma/COPD (59.3 +/- 26.0 vs 39.7 +/- 14.8 1/kW, P = .003) and trended higher compared to other patients with dyspnea (49.2 +/- 22.0, P = .10). Postural changes in mean CI were lower in AHF (-0.20 +/- 0.84 L min(-1) m(-2)) vs asthma/COPD (1.20 +/- 1.23 L min(-1) m(-2); P = .002) and other dyspnea patients (0.82 +/- 0.91 L min(-1) m(-2); P = .007). CONCLUSION: Patients with AHF have greater TFC but lower CI responses to postural changes compared to patients with asthma and COPD. Knowledge of these changes may help rapidly differentiate AHF from asthma and COPD in the ED. PMID- 21030190 TI - The need for dental care among adults presenting to an urban ED. AB - OBJECTIVE: The study aimed to estimate the prevalence of need for dental care among patients in the ED and assess associated characteristics. METHODS: This was a cross-sectional study conducted in the emergency department (ED) of a level I trauma center between June 1 and August 31, 2009. All ED patients were prospectively screened during randomly selected 8-hour blocks of time; consenting patients completed a survey on sociodemographics and health. The treating clinician completed an oral health examination to determine the patient's need for dental care as none (continue usual care), early (need to be seen soon), or urgent (need to be seen immediately). Data were analyzed using logistic regression. RESULTS: There were 4670 patients who presented to the ED, 2787 (59.7%) were eligible, 1190 (63.2%) consented and enrolled, and 653 (54.9%) had a dental examination. Of these, 388 (59.4%; 95% confidence interval [CI], 56%-63%) had no need for dental care, 199 (30.5%; 95% CI, 27%-34%) had an "early need," and 66 (10.1%; 95% CI, 8%-12%) had an "urgent need." Logistic regression showed the need for dental care was associated with age, ethnicity, and having not had a routine checkup/cleaning in the last 3 years. CONCLUSIONS: Of the patients presenting to the ED, 40.6% were in some need of dental care. This need was not associated with insurance or socioeconomic status as shown in previous studies. Age, ethnicity, and no routine oral care in the last 3 years were all associated with early/urgent need for oral health care. PMID- 21030191 TI - The impact of prehospital activation of the cardiac catheterization team on time to treatment for patients presenting with ST-segment-elevation myocardial infarction. AB - OBJECTIVE: We sought to evaluate the accuracy of emergency medical services (EMS) activation of the cardiac catheterization laboratory (CCL) for patients with ST elevation myocardial infarction (STEMI) and its impact on treatment intervals from dispatch to reperfusion. METHODS: We conducted a before-and-after cohort study of patients presenting via EMS with prehospital electrocardiogram findings consistent with STEMI. Before August 20, 2007, percutaneous coronary intervention was initiated after patient arrival. Afterward, EMS providers could activate the CCL if the prehospital electrocardiogram automated interpretation indicated STEMI. All interval times from EMS dispatch to percutaneous coronary intervention were measured via synchronized timepieces. RESULTS: A total of 53 patients, 14 before and 39 after prehospital activation, were included. Emergency medical services CCL activation was 79.6% sensitive (95% confidence interval [CI], 65.2% 89.3%) and 99.7% specific (95% CI, 99.1%-99.9%). Mean door-to-hospital electrocardiogram and mean CCL-to-reperfusion times were unaffected by the intervention. Prehospital activation of the CCL significantly improved mean door to-balloon (D2B) time by 18.2 minutes (95% CI, 7.69-28.71 minutes; P = .0029) and door-to-CCL by 14.8 minutes (95% CI, 6.20-23.39 minutes; P = .0024). Improvements in D2B were independent of presentation during peak hours (F ratio = 17.02, P < .0001). There were significant time savings reflected in all EMS intervals: 20.7 minutes (95% CI, 9.1-32.3 minutes; P = .0015) in mean dispatch-to-reperfusion time, 22.2 minutes (95% CI, 11.45-32.95 minutes; P = .0003) in mean first medical contact-to-reperfusion time, and 20 minutes (95% CI, 10.95-29.05 minutes; P = .0001) in recognition-to-reperfusion time. CONCLUSIONS: Emergency medical service providers can appropriately activate the CCL for patients with STEMI before emergency department arrival, significantly reducing mean D2B time. Significant reduction is demonstrated throughout EMS intervals. PMID- 21030192 TI - Etomidate for procedural sedation in the elderly: a retrospective comparison between age groups. AB - OBJECTIVE: The objective of the study was to compare the complication rate and length of stay (LOS) between the elderly (65 years and older) and the adult (18 64 years old) populations when etomidate is used for procedural sedation in the emergency department (ED). METHODS: A retrospective analysis was performed. Electronic medical records selected all patients who received etomidate in the ED from June 2004 to June 2008. Patients younger than 18 years and those who were intubated were excluded. To account for correlated errors, only first-time visits to the ED were used. RESULTS: There were 31 (16%) patients who experienced a complication: 9 (20%) elderly patients compared with 22 (14.8%) adult patients. No significant difference existed between the age groups and adverse effects. The adult mean LOS was 205 minutes, and the elderly LOS was 225 minutes. There was no significant difference between age groups and adverse effects when compared with LOS. Among patients who experienced a complication, mean LOS was 267 minutes: 252 minutes in the elderly age group and 273 minutes in the adult. Among patients who did not experience a complication, the mean LOS in the elderly and adult age groups was 219 and 193 minutes, respectively, with an overall LOS of 199 minutes. There was a statistical significance (P <= .05) between adverse effect and LOS. Patients who experienced a complication remained in the ED for 68 more minutes. CONCLUSION: Etomidate remains as safe and effective an alternative for procedural sedation in the elderly as it is in the general aged population. PMID- 21030193 TI - Linguistic features of power dynamics in triadic dementia diagnostic conversations. AB - OBJECTIVE: The purpose of this study was to examine linguistic expressions of power during dementia diagnosis disclosure. METHODS: Videotapes of dementia diagnosis disclosure sessions were reviewed to examine linguistic features of 86 physician-patient-companion triads. Verbal dominance and pronoun use were measured as indications of power. RESULTS: Physicians dominated the conversation, speaking 83% of the total time. Patients spoke more than companions (10% versus 6%). Dementia status was only related to the amount of time companions spent talking. Physicians used fewer first person singular and more first person plural pronouns than patients and companions. Power indices did not predict anxiety, depression, or satisfaction with the medical visit. CONCLUSION: During the disclosure of a dementia diagnosis, physicians tend to dominate the conversation, exerting their social status through a variety of linguistic features. Patients and companions are not more distressed or dissatisfied as a result and exert their own subtle attempts to assert their role in the conversation. PRACTICE IMPLICATIONS: Recognition of a hierarchical structure within healthcare interactions may be the first step toward maximizing patient outcomes. Evaluating patient expectations and preferences regarding physician communication style may be the most effective way of promoting patient-centered healthcare communication. PMID- 21030194 TI - Self-management problem solving for adolescents with type 1 diabetes: intervention processes associated with an Internet program. AB - OBJECTIVE: Describe intervention processes associated with an Internet self management problem solving program for adolescents with type 1 diabetes, and relate participant characteristics to program use. METHODS: Forty-one adolescents with type 1 diabetes, aged 13-17, participated in an Internet intervention. RESULTS: Participants reported psychosocial self-management barriers related to social issues (45%), time pressures (22%), and emotions (25%). Most adolescents (76%) completed the two guided problem solving cycles, and most (97%) problems were appropriate and specific to diabetes. Of the 61 diabetes problems reported, 92% were mostly or completely solved. Baseline hemoglobin A1c, diabetes duration, and age were not related to online activities, however females posted more often to the forum (U=130.0, Z=2.13, p=.033). The majority of parents (87%) interacted with their child about the website. CONCLUSION: Adolescents experience psychosocial barriers to self-management that can be addressed by teaching problem solving via the Internet. PRACTICE IMPLICATIONS: An Internet self management problem solving program with minimal external support provides a viable option for diabetes clinics to improve pediatric diabetes outcomes. PMID- 21030195 TI - Thirty-day mortality and late survival with reinterventions and readmissions after open and endovascular aortic aneurysm repair in Medicare beneficiaries. AB - OBJECTIVES: Late survival is similar after open and endovascular abdominal aortic aneurysm (AAA) repair (EVAR), despite a perioperative benefit with EVAR. AAA related reinterventions are more common after EVAR, whereas laparotomy-related reinterventions are more common after open repair. The effect of reinterventions on survival, however, is unknown. We therefore evaluated the rate of reinterventions and readmission after initial AAA repair, 30-day mortality, and the effect on long-term survival. METHODS: We identified AAA-related and laparotomy-related reinterventions for propensity score-matched cohorts of 45,652 Medicare beneficiaries undergoing EVAR and open repair from 2001 to 2004. Follow up was up to 6 years. Hospitalizations for ruptured AAA without repair and for bowel obstruction or ventral hernia without abdominal surgery were also recorded. Event rates were calculated per year and are presented through 6 years of follow up as events per 100 person-years. Thirty-day mortality was calculated for each reintervention or readmission. RESULTS: Through 6 years, overall reinterventions or readmissions were similar between repair methods but slightly more common after EVAR (7.6 vs 7.0/100 person-years; relative risk [RR], 1.1; P < .001). Overall 30-day mortality with any reintervention or readmission was 9.1%. EVAR patients had more ruptures (0.50 vs 0.09 [RR, 5.7; P < .001]), with a mortality of 28%, but these were uncommon. EVAR patients also had more AAA-related reinterventions through 6 years (3.7 vs 0.9 [RR, 4.0; P < .001]; mortality, 5.6%), most of which were minor endovascular reinterventions (2.4 vs 0.2 [RR, 11.4; P < .001]), with a 30-day mortality of 3.0%. However, minor open (0.8 vs 0.5 [RR, 1.4; P < .001]; mortality, 6.9%) and major reinterventions (0.4 vs 0.2 [RR, 2.4; P < .001]; mortality, 12.1%) were also more common after EVAR than open repair. Conversely, EVAR patients had fewer laparotomy-related reinterventions than open patients (1.4 vs 3.0 [RR, 0.5; P < .001]; mortality, 8.1%) and readmissions without surgery (2.0 vs 2.7 [RR, 0.7; P < .001]; mortality 10.9%). Overall, reinterventions or readmission accounted for 9.6% of all EVAR deaths and 7.6% of all open repair deaths in the follow-up period (P < .001). CONCLUSIONS: Reintervention and readmission are slightly higher after EVAR. Survival is negatively affected by reintervention or readmission after EVAR and open surgery, which likely contributes to the erosion of the survival benefit of EVAR over time. PMID- 21030196 TI - An "off the shelf" vascular allograft supports angiogenic growth in three dimensional tissue engineering. AB - OBJECTIVES: Dense angiogenic sprouting occurs from arteriovenous loops (AVLs) incorporating autologous vein grafts inserted into empty plastic chambers in vivo. The purpose of this study was to determine if angiogenesis from the AVL was limited by substituting an "off the shelf" cold-stored allograft vein instead of an autologous vein. METHODS: Four Sprague Dawley rat groups (two AVL configurations * two chamber types) were established for both 2-week and 6-week harvest. Control AVLs were autologous femoral vein grafts harvested from the left femoral vein that were surgically inserted between the cut femoral artery and vein on the right side. Experimental "allograft" AVLs were rat femoral veins cold stored (4 degrees C, sterile) for 4 to 7 weeks and then microsurgically interposed between the right femoral artery and vein of an unrelated rat. The two AVL types were inserted in one of two plastic chamber types--smooth or perforated. At harvest, the AVL constructs were checked for patency, weighed, their volume determined, and histology undertaken. Morphometric assessment of percent and absolute volume of major tissue components (including blood vessels) at 6 weeks was completed. RESULTS: There were no significant differences between autograft and allograft groups in construct weight, volume, or morphology at 2 or 6 weeks. No statistical differences occurred in the percent or absolute vascular volume of AVLs incorporating a cold-stored allograft vs autologous vein grafts at 6 weeks regardless of the chamber type. However, perforated chambers caused significant increases in construct weight (P = .015), volume (P = .006), and percent and absolute connective tissue volume at 6 weeks (P = .001) compared to smooth chamber constructs, regardless of the graft type. CONCLUSION: Cold-stored small-caliber allografts interposed in AVLs do not inhibit microcirculatory development and can be used in composite tissue engineering. PMID- 21030197 TI - Iliac vein stenting in postmenopausal leg swelling. AB - BACKGROUND: Leg swelling in menopausal women is well known. Prevailing concept in primary care is that it is polycentric and a treatable cause may not be found. Patients are placed on empiric diuretics often without benefit. Our clinical experience indicates that iliac venous vein obstruction is the core cause; a variety of secondary factors common in postmenopausal women precipitate symptoms. PATIENTS AND METHODS: A total of 163 limbs in 150 postmenopausal women (>= 55 years of age) with leg swelling unresponsive to conservative therapy underwent intravascular ultrasound-guided iliac vein stenting over an 11-year period. Preoperative investigations included duplex, airplethysmography, venous pressure tests, contrast studies, and lymphangiography. The postmenopausal group constituted 9% of all limbs (n = 1760) stented for chronic venous disease (CVD) during the same period and 18% of those stented for swelling (n = 922). Median age was 67 (range, 55-92) and left-to-right ratio 2:1. RESULTS: Iliac vein obstruction was "primary" (nonthrombotic) in 65% and postthrombotic in 35% of limbs; 35% of limbs had obstruction only and 65% combined obstruction/reflux. Lymphatic dysfunction was present in 21% of the limbs. Mean intravascular ultrasound area stenosis was 68% +/- 22 SD. Mean follow-up was 22 months (+/- 26 SD) (range, 1-113 months). Secondary stent patency (6 years) was 100% in primary and 91% in postthrombotic limbs; overall 98%. Swelling improved significantly (P < .0001) from preoperative grade 2.5 (+/- 0.8 SD) to postoperative grade 1.2 (1.2 SD). Associated pain also improved significantly (P < .0001) from preoperative visual analog scale 3.5 (+/- 3 SD) to postoperative 0.9 (2.1 +/- SD). Quality-of life (CIVQ) scores improved significantly in every category and overall (P < .0001). CONCLUSIONS: Patients with postmenopausal leg swelling often have obstructive venous pathology even though suggestive venous history and other signs are often absent. Morbidity arises from painful swelling that affects mobility, quality of life, and ability of self-care at later stages of life. Outpatient percutaneous iliac vein stenting affords substantial symptom relief and improvement in quality-of-life measures. Recognition of the clinical complex as a distinct entity of venous origin may lead to greater awareness and effective treatment. PMID- 21030198 TI - Treatment of peripheral arterial disease using stem and progenitor cell therapy. AB - Peripheral arterial disease (PAD) is a highly prevalent atherosclerotic syndrome associated with significant morbidity and mortality. PAD is most commonly caused by atherosclerosis obliterans (ASO) and thromboangiitis obliterans (TAO), and can lead to claudication and critical limb ischemia (CLI), often resulting in a need for major amputation and subsequent death. Standard treatment for such severe cases of PAD is surgical or endovascular revascularization. However, up to 30% of patients are not candidates for such interventions, due to high operative risk or unfavorable vascular involvement. Therefore, new strategies are needed to offer these patients a viable therapeutic option. Bone-marrow derived stem and progenitor cells have been identified as a potential new therapeutic option to induce angiogenesis. These findings prompted clinical researchers to explore the feasibility of cell therapies in patients with peripheral and coronary artery disease in several small trials. Clinical benefits were reported from these trials including improvement of ankle-brachial index (ABI), transcutaneous partial pressure of oxygen (TcO(2)), reduction of pain, and decreased need for amputation. Nonetheless, large randomized, placebo-controlled, double-blind studies are necessary and currently ongoing to provide stronger safety and efficacy data on cell therapy. Current literature is supportive of intramuscular bone marrow cell administration as a relatively safe, feasible, and possibly effective therapy for patients with PAD who are not subjects for conventional revascularization. PMID- 21030199 TI - Open abdominal aortic aneurysm repair is feasible and can be done with excellent results in octogenarians. AB - OBJECTIVE: The purpose of this study was to determine the feasibility of open abdominal aortic aneurysm (AAA) repair in octogenarians during a time period of multiple commercially available endografts, in which only proximal aneurysms or the most challenging anatomy are not stented. METHODS: A retrospective review was performed of all patients aged >= 80 years undergoing open AAA repair over a 7 year period (2003-2009) at a single academic medical center. Demographic data, aneurysm characteristics, comorbidities, operative results, perioperative complications, length of stay, and late outcomes were analyzed. RESULTS: Sixty five patients were identified (men, n = 27) with a median age of 82 years (80-89 years old). Mean aneurysm size was 6.7 cm. Morphology consisted of type IV thoracoabdominal (n = 19), suprarenal (n = 14), pararenal (n = 19), and infrarenal (n = 13). Eighty-five percent of cases were performed electively. A tube graft was used in 58 patients, and the left renal artery was bypassed in 33 patients. Fifty-two patients required a suprarenal or supraceliac clamp, with a mean proximal clamp time of 22 minutes. Mean estimated blood loss was 1800 mL. Mortality was 6% at 30 days. Overall morbidity was 42%, most commonly an arrhythmia (25%). Major complication rate was 18%. Median intensive care unit (ICU) and hospital length of stay was 3 and 9 days, respectively. Sixty-one percent of patients were discharged directly home. Six patients developed acute renal failure, although none progressed to dialysis. Mean serum creatinine was 1.3 mg/dL preoperatively and 1.5 mg/dL at discharge. One patient developed bowel necrosis (sigmoid colon) requiring resection. Follow-up ranged from 1 to 81 months (mean, 24 months). Three-year survival was 79%. CONCLUSION: With an increasing population of elderly patients, vascular surgeons are continually confronted with patients over 80 years of age. Our patients consisted of those not anatomically suitable for endovascular aortic aneurysm repair. Despite a predominance of proximal aneurysms, our results demonstrate excellent rates of morbidity and mortality. Thus, open AAA repair can be done safely and effectively in octogenarians, and age alone should not exclude this form of repair. PMID- 21030200 TI - Aneurysmal iliac arteries do not portend future iliac aneurysmal enlargement after endovascular aneurysm repair for abdominal aortic aneurysm. AB - OBJECTIVES: The purpose of this study was to examine the fate of aneurysmal iliac arteries managed during endovascular aneurysm repair (EVAR) for abdominal aortic aneurysm (AAA). METHODS: We analyzed data from the Cook Zenith trial. Follow-up was at 1 month, 6 months, 12 months, and then annually for 5 years. Patients were evaluated according to the largest iliac artery diameter: group A (>= 20 mm) and group B (< 20 mm). These groups were further subdivided based on iliac artery growth >= 5 mm during follow-up. The Fisher exact test and chi(2) test were used. RESULTS: Of 736 patients treated, 671 had a follow-up examination (group A = 274). In group A, 220 (80%) were treated with flared limbs in the common iliac artery. Group A did not demonstrate increased iliac growth as compared to group B. Furthermore, both groups had a similar percentage of patients that experienced iliac artery expansion of 32.1% and 31.5%, respectively. Extension to the external iliac artery did not affect growth (P = .4). No difference was noted in the need for secondary interventions between groups. However, group A patients that did not experience growth were more likely to develop a distal type I endoleak than group B patients who did not develop growth (P = .03). There was no difference in serious adverse events (SAEs) between groups (P = .51). However, patients that developed iliac artery growth in either group were less likely to have an SAE compared to patients who did not experience growth (P = .035). There was no difference in the mean percent oversizing of the iliac limbs between groups A and B. However, the mean percent oversizing in groups A and B that had iliac artery growth was significantly higher than in those that demonstrated no growth (P < .01). CONCLUSION: Aneurysmal iliac arteries managed by flared limbs or external iliac extensions at the time of EVAR for AAA do not demonstrate future iliac growth, increased rate of secondary interventions, or SAEs compared to patients with normal iliac arteries. This suggests that aneurysmal iliac arteries can be safely treated with appropriately sized limbs landed in the common or external iliac artery. PMID- 21030201 TI - Subintimal angioplasty of chronic total occlusion in iliac arteries: a safe and durable option. AB - BACKGROUND: Traditionally, aortobifemoral bypass has been the intervention of choice for iliac artery chronic total occlusions (CTOs). However, it is associated with significant morbidity and mortality, limiting its use in high risk patients. To reduce procedural risk, subintimal angioplasty (SIA) for femoropopliteal CTO has been utilized by many, but few have extended this endovascular technique to treating iliac artery CTOs. We present our experience with 101 successful SIAs for iliac artery CTOs. METHODS: A retrospective review of consecutive patients with iliac artery CTOs treated with subintimal angioplasty from June 2000 to January 2009 was completed. Demographic and risk factor data were obtained, along with procedural data. Primary and secondary patency, survival, freedom from claudication, and limb salvage rates were determined by Kaplan-Meier survival analysis. Univariate and multivariate analyses were completed to identify factors adversely affecting primary patency. RESULTS: One hundred twenty patients underwent an attempted SIA of an iliac artery CTO, and 101 iliac artery CTOs were successfully treated, giving a technical success rate of 84%. Technical failure was due to the inability to re enter the lumen in all cases. Indications for intervention were lifestyle altering claudication in 64 patients (63%) and critical limb ischemia (CLI), in 37 (37%). Eighty-five patients underwent percutaneous SIA, while 11 patients underwent a combined SIA with surgical outflow procedure. Lesions were classified as TransAtlantic InterSociety Consensus (TASC) B, 39 (39%); TASC C, 27 (27%); and TASC D, 35 (35%). In 82 (81%) lesions, stents were deployed with an average of 1.2 (range, 0-3) stents utilized. A re-entry device was used in 14 (14%) lesions. Major complication rate was 3.0%, with a 30-day mortality rate of 1.0%. Primary and secondary patency rates at 1, 2, and 3 years were 86% and 94%, 76% and 92%, and 68% and 80%, respectively. Survival rate was 67% at 5 years, reflecting the poor health of this cohort. Limb salvage for CLI patients at 1 and 5 years was 97% and 95%, respectively. Freedom from claudication at 1 and 3 years was 89% and 73%. Univariate analysis identified hyperlipidemia, coronary artery disease, and prior surgical bypass in treated limb as factors for loss of primary patency; however, on multivariate analysis, no factors remained statistically significant. CONCLUSION: This study demonstrates that SIA of iliac CTOs is feasible and can be performed safely and effectively, even in high-risk patients. Excellent patency and limb salvage rates can be achieved. In our experience, the safety and durability of SIA makes it an attractive first-line therapy for iliac artery occlusive disease. PMID- 21030202 TI - Arthroscopic debridement of the talonavicular joint using dorsomedial and dorsolateral portals: a cadaveric study of safety and access. AB - PURPOSE: The purpose of this study was to examine the safety and access talonavicular arthroscopy provides for the purpose of arthrodesis through dorsomedial and dorsolateral portals in a cadaveric model. METHODS: The talonavicular joints of 8 cadaveric specimens were arthroscopically debrided, by use of a dorsomedial instrumentation portal and a dorsolateral visualization portal. The specimens were dissected with the arthroscopic equipment left in place, the distances from the edge of the instrument to the neurovascular structures were measured, and the specimens were then examined for signs of damage. Finally, the naviculars and tali were removed, and the percentage of debrided subchondral bone was determined by use of ImageJ software (National Institutes of Health, Bethesda, MD). RESULTS: Examination of the talonavicular joint showed mean subchondral debridement of 98.6% of the navicular and 83.2% of the talus. The dorsomedial portal had a median distance of 4.5 mm, 10.5 mm, and 7 mm to the superficial peroneal nerve, the medial terminal branch of the deep peroneal nerve, and the dorsalis pedis, respectively. The dorsolateral portal had a median distance of 1 mm to the lateral branch of the deep peroneal nerve, with the nerve found resting on the arthroscope in 2 specimens. CONCLUSIONS: Arthroscopic debridement of the talonavicular joint is possible. Because of the risk of damage to the lateral terminal branch of the deep peroneal nerve, an alternative to the dorsolateral portal should be considered. CLINICAL RELEVANCE: This study provides evidence that arthroscopic assisted talonavicular arthrodesis is possible but that further research is needed to ensure the safety of the technique. PMID- 21030203 TI - Biological knee reconstruction: a systematic review of combined meniscal allograft transplantation and cartilage repair or restoration. AB - PURPOSE: Combined meniscal allograft transplantation (MAT) and cartilage repair or restoration is a recognized treatment for patients with painful, meniscus deficient knees and full-thickness cartilage damage. The purpose of this systematic review was to compare outcomes after combined MAT and cartilage repair/restoration with the outcomes of isolated MAT or cartilage repair/restoration. METHODS: Multiple databases were searched with specific inclusion and exclusion criteria for clinical outcome studies after combined MAT and cartilage repair or restoration. RESULTS: Six studies were identified for inclusion. In total 110 patients underwent combined MAT/cartilage repair or restoration (medial compartment in 66 and lateral compartment in 44). Patients underwent MAT and either autologous chondrocyte implantation (n = 73), osteochondral allograft (n = 20), osteochondral autograft transfer (n = 17), or microfracture (n = 3). Thirty-six patients underwent additional concurrent surgeries (high tibial or distal femoral osteotomy, cruciate or collateral ligament reconstruction, and hardware removal). All clinical outcomes were improved at final follow-up (mean, 36 months). In 4 of 6 studies, overall outcomes of combined surgery were equivalent to those of either procedure performed in isolation. In 2 studies outcomes of combined surgery were not as good as those of either procedure performed in isolation. Failure occurred in 12% of patients who underwent combined MAT and cartilage restoration, and they required revision surgery. Most failures (85%) of combined surgery were due to failure of the MAT (as opposed to the cartilage technique). One-half of all patients required at least 1 surgery after the index procedure before final follow-up. CONCLUSIONS: Clinical outcomes after combined MAT and cartilage repair/restoration are similar to those after either procedure in isolation. Despite low rates of complications and failures, there is a high rate of subsequent surgery after combined MAT and cartilage repair or restoration. LEVEL OF EVIDENCE: Level IV, systematic review of Level IV studies. PMID- 21030204 TI - Repair of radial tears and posterior horn detachments of the lateral meniscus: minimum 2-year follow-up. AB - PURPOSE: The aim of this study was to show that repair of posterior radial tears and horn detachments of the lateral meniscus is possible and to assess the outcomes. METHODS: A retrospective review of 24 patients who had repair of a posterior defunctioning tear of the lateral meniscus combined with anterior cruciate ligament reconstruction was undertaken. Patients completed a follow-up postal questionnaire that included Lysholm, subjective International Knee Documentation Committee (IKDC), and Tegner scoring systems. RESULTS: Eight patients had suture repair of a lateral meniscal radial tear. The mean Lysholm, IKDC, and Tegner scores were 86.9 (SD, 11.6), 81.6 (SD, 13.9), and 5.8 (SD, 2.7), respectively, at a mean follow-up of 70.5 months (range, 29.0 to 168.0 months). Subsequent arthroscopy in 2 patients confirmed meniscal healing. Sixteen patients underwent a posterior horn reattachment. The mean Lysholm, subjective IKDC, and Tegner scores were 86.1 (SD, 13.3), 84.3 (SD, 17.0), and 6.5 (SD, 2.1), respectively, at a mean follow-up of 53.6 months (range, 26.0 to 116.0 months). Three patients had subsequent magnetic resonance imaging and/or arthroscopy that indicated meniscal healing. Two further patients had reinjury, and magnetic resonance imaging and/or arthroscopy showed that their repairs had failed. CONCLUSIONS: Posterior radial tears that extend to the capsule and posterior horn detachments of the lateral meniscus are frequently amenable to repair. In this study 22 of 24 repairs functioned successfully over a mean follow-up of 58.6 months (range, 26.0 to 168.0 months). LEVEL OF EVIDENCE: Level IV, therapeutic case series. PMID- 21030205 TI - Biceps tenodesis with interference screw fixation: a biomechanical comparison of screw length and diameter. AB - PURPOSE: To evaluate the effect of screw length and diameter on the mechanical properties of biceps tenodesis (BT) with an interference screw in 2 different locations (proximal and distal). METHODS: We randomized 42 fresh-frozen human cadaveric shoulders (mean age, 65 +/- 8 years) into 6 groups (n = 7): arthroscopic proximal BT using 7 * 15-, 7 * 25-, 8 * 15-, or 8 * 25-mm interference screws or distal subpectoral BT with 7 * 15- or 8 * 15-mm interference screws. Each repaired specimen was mounted onto a materials testing machine, preloaded to 5 N for 2 minutes, cycled from 5 to 70 N for 500 cycles (1 Hz), and loaded to failure (1 mm/s). Displacement during cyclical loading, pullout stiffness, and ultimate load to failure were computed, and the mechanism of failure was noted. RESULTS: All failures occurred at the tendon-screw interface. There was no statistically significant difference in ultimate displacement among all groups in the ultimate load to failure, displacement at peak load, and stiffness. CONCLUSIONS: There is no difference in ultimate load to failure, displacement at peak load, and stiffness of BT with regard to screw length or diameter at both proximal and distal tenodesis locations. These data would support use of a smaller-diameter and shorter implant for BT both proximally and distally. CLINICAL RELEVANCE: The results may serve as a guide to the orthopaedic surgeon performing proximal BT in selecting the appropriate interference screw. When possible, we recommend using the smallest screw size available to minimize risk of stress fracture at the tenodesis site. PMID- 21030206 TI - [Pathophysiology of osteoarthritis: updated concepts]. AB - Osteoarthritis is a whole joint disease including: cartilage, synovial tissue, subchondral bone, ligaments, muscles, and tendons. Cartilage is the main target tissue of the disease. Mechanical stress is a key regulator in osteoarthritis development and progression. Inflammation is a key regulator in osteoarthritis development and progression. The weight of genetic factors, mechanical stress, inflammation, and hormonal status is variable from a joint to another. PMID- 21030207 TI - The determinants of daily function in children with cerebral palsy. AB - The aim of this study was to identify determinants of daily function in a population-based sample of children with cerebral palsy (CP). The study took into consideration factors from the entire scope of the International Classification of Functioning, Disability, and Health (ICF). Furthermore, the determinants of daily function were examined from the perspectives of capacity and performance respectively. A total of 216 children with CP (mean age 8.19 years, SD 3.39 years) and their caregivers participated in the study. The potential determinants of daily function from the dimensions of health condition, body functions and structures, environmental and personal factors of the ICF were collected. Stepwise multiple regression models showed that child's age, grade, preferred hand, educational placement, severity of gross and fine motor impairment, and prosocial behavior were important determinants, accounting for 88.29% of the variance of daily capacity. The aforementioned variables together with birth order were determinants of performance of daily function, and accounted for 89.53% of the variance in that performance. Knowledge of determinants of daily function helps clinicians and educators to plan intervention and educational programs targeted at these determinants to improve capacity and performance in daily function for children with CP. PMID- 21030208 TI - Sublingual vein extraction algorithm based on hyperspectral tongue imaging technology. AB - Among the parts of the human tongue surface, the sublingual vein is one of the most important ones which may have pathological relationship with some diseases. To analyze this information quantitatively, one primitive work is to extract sublingual veins accurately from tongue body. In this paper, a hyperspectral tongue imaging system instead of a digital camera is used to capture sublingual images. A hidden Markov model approach is presented to extract the sublingual veins from the hyperspectral sublingual images. This approach characterizes the spectral correlation and the band-to-band variability using a hidden Markov process, where the model parameters are estimated by the spectra of the pixel vectors forming the observation sequences. The proposed algorithm, the pixel based sublingual vein segmentation algorithm, and the spectral angle mapper algorithm are tested on a total of 150 scenes of hyperspectral sublingual veins images to evaluate the performance of the new method. The experimental results demonstrate that the proposed algorithm can extract the sublingual veins more accurately than the traditional algorithms and can perform well even in a noisy environment. PMID- 21030209 TI - The "Big 5" and beyond: nurses, paid carers, and adults with developmental disability discuss communication needs in hospital. AB - Adults with developmental disability and little or no speech need to communicate with nurses in hospital to (a) express physical needs, (b) discuss health, (c) convey intelligence and emotions, (d) connect socially, and (e) control the environment. All stakeholders need access to a variety of communication strategies to support communication of these needs. PMID- 21030210 TI - Biomechanics of the upper airway: Changing concepts in the pathogenesis of obstructive sleep apnea. AB - Obstructive sleep apnea (OSA) is a disorder characterized by repetitive, episodic collapse of the pharyngeal airway. Over the last two decades, understanding of the pathophysiology of sleep disordered breathing, which includes OSA, has improved. Once thought to be predominately related to anatomic constriction of the maxillomandibular complex, central nervous system regulation of breathing is now recognized as a significant contributor to the pathogenesis of OSA. Ventilator control, the central response to chemoreceptor phenomena, has important implications for oral and maxillofacial surgeons who treat OSA, particularly for patients who appear refractory to treatment with maxillomandibular advancement (MMA). The purpose of this article is to review the biomechanics of the upper airway as it relates to the pathophysiology of OSA, to discuss emerging concepts of ventilator control mechanisms in normal sleep versus sleep-disordered breathing and to discuss the concept of complex sleep apnea, a new category of sleep disordered breathing with both obstructive and central features. PMID- 21030211 TI - Validation of new soft tissue software in orthognathic surgery planning. AB - This study tests computer imaging software (SurgiCase-CMF((r)), Materialise) that enables surgeons to perform virtual orthognathic surgical planning using a three dimensional (3D) utility that previews the final shape of hard and soft tissues. It includes a soft tissue simulation module that has created images of soft tissues altered through bimaxillary orthognathic surgery to correct facial deformities. Cephalometric radiographs and CT scans were taken of each patient before and after surgery. The surgical planning system consists of four stages: CT data reconstruction; 3D model generation of facial hard and soft tissue; different virtual surgical planning and simulation modes; and various preoperative previews of the soft tissues. Surgical planning and simulation is based on a 3D CT reconstructed bone model and soft tissue image generation is based on physical algorithms. The software rapidly follows clinical options to generate a series of simulations and soft tissue models; to avoid TMJ functional problems, pre-surgical plans were evaluated by an orthodontist. Comparing simulation results with postoperative CT data, the reliability of the soft tissues preview was >91%. SurgiCase((r)) software can provide a realistic, accurate forecast of the patient's facial appearance after surgery. PMID- 21030212 TI - Chronic kidney disease and heart failure--Bidirectional close link and common therapeutic goal. AB - Chronic kidney disease (CKD) is common and the estimated prevalence is about 9 13% in the general adult population. CKD is defined by the presence of kidney damage or decreased glomerular filtration rate. Individuals with CKD have a far greater likelihood of cardiovascular death than progression to end-stage renal disease. Heart failure (HF) is a complex clinical syndrome that can result from any structural or functional cardiac disorder and the prevalence is reported to be 2-3% in the general population. The prognosis of HF patients is still poor despite recent advances in HF treatment. Both diseases are major and growing public health problems because aging of the population contributes to the increasing incidence of those diseases. More than 40% of HF patients have CKD and the close relationship between CKD and HF worsens their prognoses. All physicians must evaluate kidney function using estimated glomerular filtration rate calculated by the new Japanese equation in patients with HF. Accurate evaluation of pathophysiology between the two diseases and appropriate intervention are necessary to improve the prognosis of patients with the diseases. PMID- 21030213 TI - Kynurenine 3-monooxygenase (KMO) polymorphisms in schizophrenia: an association study. PMID- 21030214 TI - A closer look at siblings of patients with schizophrenia: the association of depression history and sex with cognitive phenotypes. AB - BACKGROUND: Siblings of patients with schizophrenia show impaired cognition and an increased prevalence of depression history. Although sex has been shown to moderate cognition in patients, this effect has not been examined in siblings. Here we elucidate how a history of depression and sex influences cognition in siblings unaffected by schizophrenia. METHODS: Unaffected siblings of patients with schizophrenia and unrelated healthy controls were evaluated neuropsychologically and completed structured clinical interviews. Participants with a depression history or no psychiatric history were selected for the sample. Cognitive performance of siblings (n=366) and controls (n=680) was first examined. Second, cognition of participants with a depression history and those without a psychiatric history was compared while additionally investigating the role of schizophrenia risk and sex. RESULTS: Relative to controls, siblings, with and without a psychiatric history, demonstrated significant (p<.05) cognitive deficits. Depression history impaired cognition in siblings, but not in controls; whereas sex affected cognition in both siblings and controls. In siblings alone, sex significantly interacted with depression history to influence cognition. This interaction revealed that in male--but not female--siblings a history of depression was associated with greater cognitive impairments. CONCLUSION: A history of depression impairs cognition in siblings, but not in controls. Moreover, depression history interacts with sex and demonstrates that only cognition in male siblings is significantly and additionally compromised by a history of depression. This interaction may be an important consideration for future phenotype and genetic association studies. PMID- 21030216 TI - Shared changes in gene expression in frontal cortex of four genetically modified mouse models of depression. AB - This study aimed to identify whether genetic manipulation of four systems implicated in the pathogenesis of depression converge on shared molecular processes underpinning depression-like behaviour in mice. Altered 5HT function was modelled using the 5-HT transporter knock out mouse, impaired glucocorticoid receptor (GR) function using an antisense-induced knock down mouse, disrupted glutamate function using a heterozygous KO of the vesicular glutamate transporter 1 gene, and impaired cannabinoid signalling using the cannabinoid 1 receptor KO mouse. All 4 four genetically modified mice were previously shown to show exaggerated helpless behaviour compared to wild-type controls and variable degrees of anxiety and anhedonic behaviour. mRNA was extracted from frontal cortex and hybridised to Illumina microarrays. Combined contrast analysis was used to identify genes showing different patterns of up- and down-regulation across the 4 models. 1823 genes were differentially regulated. They were over represented in gene ontology categories of metabolism, protein handling and synapse. In each model compared to wild-type mice of the same genetic background, a number of genes showed increased expression changes of >10%, other genes showed decreases in each model. Most of the genes showed mixed effects. Several previous array findings were replicated. The results point to cellular stress and changes in post-synaptic remodelling as final common mechanisms of depression and resilience. PMID- 21030215 TI - ID3 mediates X-ray-induced apoptosis of keratinocytes through the regulation of beta-catenin. AB - BACKGROUND: Ionizing radiation is used to treat many of cancers, however, it also produces unwanted side effect on normal tissues, such as radiodermatitis. We previously established an animal model for radiodermatitis, and found that X-ray irradiation induced the expression of ID3 in hairless mouse skin by cDNA microarray. OBJECTIVE: The aim of this study is to investigate the functional role of ID3 in X-ray irradiated keratinocytes. METHODS: Immunohistochemistry, RT PCR and Western blot were performed to demonstrate the ID3 induction by X-ray irradiation. HaCaT keratinocytes were transduced with the recombinant adenovirus expressing HA-ID3, and then effects on apoptosis were analyzed. RESULTS: X-ray irradiation increased markedly the ID3 protein level in epidermis of mouse skin. X-ray irradiation also induced the expression of ID3 in HaCaT keratinocytes cultured in vitro, at both mRNA and protein levels. When ID3 was overexpressed by recombinant adenovirus, apoptosis of keratinocytes were induced even in the absence of X-ray irradiation. Furthermore, overexpression of ID3 sensitized X-ray induced apoptosis. Interestingly, X-ray irradiation significantly reduced the endogenous beta-catenin level, which was related with induction of apoptosis. Similarly, overexpression of ID3 led to remarkable reduction in beta-catenin level. CONCLUSION: These results suggest that ID3 plays a role as an apoptosis inducer in response to X-ray irradiation via the regulation of endogenous beta catenin level. PMID- 21030218 TI - Determination of J coupling constants between spin-1/2 and quadrupolar nuclei in inorganic solids from spin echo and refocused INEPT experiments: a case study on AlPO4 berlinite. AB - A systematic study utilizing rotor-synchronized homonuclear ((31)P, (27)Al) and heteronuclear ({(31)P}(27)Al and {(27)Al}(31)P) spin echo, and {(27)Al}(31)P refocused INEPT experiments (employing soft pulses for selective excitation of the central transition for the quadrupolar (27)Al (I=5/2)) have been performed on AlPO(4) berlinite at 30 kHz MAS to better understand the J modulation behavior involving half-integer quadrupolar nuclei in solid materials with framework structure. Analyses of the J modulation on either the (27)Al or (31)P coherence in both the {(31)P}(27)Al and {(27)Al}(31)P spin echo experiments, and both periods of the refocused INEPT experiment yield consistent results for the (2)J(AlP) (Al-O-P) coupling constant (ca. 25 Hz). It is noted that the coupling of each (27)Al to four (31)P spins during the first ((27)Al) evolution period of the refocused INEPT, and the populations of (31)P coupled to different numbers (0 4) of (27)Al in the +/- 1/2 Zeeman states during (31)P coherence evolution, which have been neglected in previous studies, must be taken into account for proper treatment. Analysis of J modulation on the spin ((27)Al) coupled to spin-1/2 nuclei in general gives more accurate results. Weak long-range homonuclear (4)J(PP) (P-O-Al-O-P) coupling was also observed from the (31)P spin echo and INADEQUATE experiments. PMID- 21030217 TI - Distribution volume ratio of serotonin and dopamine transporters in euthymic patients with a history of major depression - a dual-isotope SPECT study. AB - Serotonin transporter (SERT) and dopamine transporter (DAT) levels differ in patients with major depression who are in a depressed state in comparison with healthy controls. The aim of this study was to examine the distribution volume ratios (DVRs) of SERT and DAT in drug-free and euthymic patients with a history of major depression. Subjects comprised 13 patients with a history of major depression and 26 sex- and age-matched healthy controls. The euthymic state of depression was defined as a score of 7 or less on the Hamilton Depression Rating Scale. The DVRs of SERT and DAT were approximated using SPECT, with [(123)I] 2 ((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine (ADAM) and [(99m)Tc] TRODAT-1 as the ligands, respectively. There were no significant differences in the DVRs of SERT or DAT between healthy subjects and euthymic patients with a history of major depression; hence, the SERT and DAT DVRs may not therefore be trait markers for patients with major depression, which helps us to understand more about the pathophysiology of depression. PMID- 21030219 TI - Influence of solution chemistry on the deposition and detachment kinetics of RNA on silica surfaces. AB - The deposition kinetics of RNA extracted from both virus and bacteria on silica surfaces were examined in both monovalent (NaCl) and divalent (CaCl(2)) solutions under a wide range of environmentally relevant ionic strength and pH conditions by utilizing a quartz crystal microbalance with dissipation (QCM-D). To better understand the RNA deposition mechanisms, QCM-D data were complemented by diffusion coefficients and zeta potentials of RNA as a function of examined solution chemistry conditions. Favorable deposition of RNA on poly-l-lysine coated (positively charged) silica surfaces was governed by the convective diffusive transport of RNA to the surfaces. The deposition kinetics of RNA on bare silica surfaces were controlled by classic Derjaguin-Landau-Verwey-Overbeek (DLVO) interactions. The presence of divalent cations (Ca(2+)) in solutions greatly enhanced the deposition kinetics of RNA on silica surfaces. Solution pH also affected the deposition behavior of RNA on silica surfaces. Release experiments showed that detachment of RNA from silica surfaces was significant in NaCl solutions, whereas, the deposited RNA on silica surfaces in CaCl(2) solutions was more likely to be irreversible. PMID- 21030220 TI - Biogenic synthesis of Ag, Au and bimetallic Au/Ag alloy nanoparticles using aqueous extract of mahogany (Swietenia mahogani JACQ.) leaves. AB - In this paper, we have demonstrated for the first time, the superb efficiency of aqueous extract of dried leaves of mahogany (Swietenia mahogani JACQ.) in the rapid synthesis of stable monometallic Au and Ag nanoparticles and also Au/Ag bimetallic alloy nanoparticles having spectacular morphologies. Our method was clean, nontoxic and environment friendly. When exposed to aqueous mahogany leaf extract, competitive reduction of Au(III) and Ag(I) ions present simultaneously in same solution leads to the production of bimetallic Au/Ag alloy nanoparticles. UV-visible spectroscopy was used to monitor the kinetics of nanoparticles formation. UV-visible spectroscopic data and TEM images revealed the formation of bimetallic Au/Ag alloy nanoparticles. Mahogany leaf extract contains various polyhydroxy limonoids which are responsible for the reduction of Au(III) and Ag(I) ions leading to the formation and stabilization of Au and Ag nanopaticles. PMID- 21030221 TI - Electrochemically deposited nanocomposite of chitosan and carbon nanotubes for detection of human chorionic gonadotrophin. AB - A new label-free amperometric immunosensor was developed for detection of human chorionic gonadotrophin (hCG) based on multiwall carbon nanotubes-chitosan (MWNTs CS) complex film and three-dimensional AuNPs-TiO(2) hybrid. Firstly, MWNTs-CS film was deposited on a glassy carbon electrode (GCE) by a simple and controllable electrodeposition method. Next, thionine (Thi), as a redox probe, was covalently bound onto the MWNTs-CS film with glutaraldehyde (GA) to obtain the Thi/MWNTs-CS film. The free amino groups of the composite membrane were used to adsorb AuNPs-TiO(2) for immobilizing human chorionic gonadotrophin antibody (anti-hCG) because of its large surface area and satisfactory biocompatibility. At last, BSA was employed to block possible remaining active sites. Under optimized conditions, the immunosensor displayed high sensitivity, good reproducibility, and a low detection limit of 0.08mIU/mL at 3 times the background noise. The ease of non-manual technique and the promising feature of biocomposite could serve as a versatile platform for constructing other biosensors. PMID- 21030222 TI - Interaction of an antidepressant buzepide methiodide with DNA immobilized on the glassy carbon electrode. AB - In the present study, a DNA-biosensor was prepared using immobilization technique to investigate the interaction between an antidepressant, buzepide methiodide (BZP) and calf thymus DNA. BZP showed a quasireversible peak in Britton-Robinson (BR) buffer of pH 5 at bare glassy carbon electrode (GCE). At DNA modified GCE, the peak potential of BZP was observed to be shifted towards positive potential revealing intercalative mode of binding. The binding constant and stoichiometry between DNA and BZP are calculated to be 1.908*10(5)M(-1) and 0.982, respectively. The spectroscopic techniques viz., spectrofluorescence and UV-vis absorption have also been employed to understand the interaction between BZP and DNA. The results serve as a reference for the interaction of BZP with DNA base pairs in the natural environment of living cells. PMID- 21030223 TI - Emulsification potential of a newly isolated biosurfactant-producing bacterium, Rhodococcus sp. strain TA6. AB - An indigenous biosurfactant producing bacterium, Rhodococcus sp. strain TA6 was isolated from Iranian oil contaminated soil using an efficient enrichment and screening method. During growth on sucrose and several hydrocarbon substrates as sole carbon source, the bacterium could produce biosurfactants. As a result of biosurfactant synthesis, the surface tension of the growth medium was reduced from 68mNm(-1) to values below 30mNm(-1). The biosurfactant was capable of forming stable emulsions with various hydrocarbons ranging from pentane to light motor oil. Preliminary chemical characterization revealed that the TA6 biosurfactant consisted of extracellular lipids and glycolipids. The biosurfactant was stable during exposure to high salinity (10% NaCl), elevated temperatures (120 degrees C for 15min) and within a wide pH range (4.0-10.0). The culture broth was effective in recovering up to 70% of the residual oil from oil saturated sand packs which indicates the potential value of the biosurfactant in enhanced oil recovery. PMID- 21030224 TI - [Having a child with sexual differentiation disorder -- how to listen to the troubled father?]. PMID- 21030225 TI - Concomitant adjuvant chemoradiotherapy with weekly low-dose cisplatin for high risk squamous cell carcinoma of the head and neck: a phase II prospective trial. AB - AIMS: Several randomised trials have tested adjuvant regimens using concomitant high-dose cisplatin and radiotherapy to improve outcome in high-risk locally advanced squamous cell head and neck cancer (HNSCC), showing a substantial increase in locoregional control and disease-free survival, despite a higher and eventually detrimental toxicity profile. The aim of the present phase II single stage prospective study was to investigate whether a weekly cisplatin-based chemoradiotherapy regimen might be able to improve patients' compliance compared with standard-dose cisplatin with similar outcome results. MATERIALS AND METHODS: Between January 2004 and November 2008, 54 patients with high-risk locally advanced HNSCC were enrolled on to this phase II trial. Patient characteristics were: median age 59.7 years, Eastern Cooperative Oncology Group performance status 1 in 72% of patients and stage IV disease in 82%, extracapsular nodal spread in 67% and positive/close surgical margins in 37%. Patients received cisplatin (30 mg/m(2)) once a week for 7-8 weeks concurrent with external beam radiotherapy delivered with a median dose of 66.6 Gy (1.8 Gy each day; five fractions/week) on the primary site and 50 Gy (2 Gy each day) for the lower neck. RESULTS: Major acute toxicity of the combined treatment, defined as grade 3-4 mucositis, was observed in 35.2% of patients. No fatal complications occurred, with 81.5% of patients completing the planned regimen. Late reactions were mild (total 16% with a grade 3 dysphagia rate of 12%). The locoregional control rate was 82%; 5 year overall and disease-free survival were 63 and 62%, respectively. CONCLUSIONS: Concomitant adjuvant chemoradiotherapy with weekly cisplatin seems to be a feasible and well-tolerated therapeutic approach in 'unfit' patients. Clinical results seem to be at least comparable with those previously reported. However, to draw any definitive conclusion, large confirmatory phase III randomised trials are demanded. PMID- 21030226 TI - High-dose vitamin C: does it exacerbate the effect of psychosocial stress on liver? Biochemical and histological study. AB - AIM: Chronic stress has been implicated as a contributing factor in liver injury. However, other factors that can contribute to the severity of stress effect in liver injury have not been well characterized. In this study, the combined effect of chronic psychosocial stress and variable dosing levels of vitamin C on liver injury, have been studied. METHODS: Stress was chronically induced using intruder method. Vitamin C was administered by oral gavage. Both biochemical and histopathological measures were undertaken. RESULTS: The results showed that low (50mg/kg/day) and moderate (150 mg/kg/day) doses of vitamin C alone or in combination with chronic stress had no effect on liver. However, combination of high dose of vitamin C (500 mg/kg/day) and chronic stress induced various histopathological liver lesions in most of animals in the group that was stressed and supplemented with high dose vitamin C. CONCLUSION: Results of this study show a dose-dependent effect for vitamin C in exacerbating stress contribution to liver injury. PMID- 21030227 TI - Comparison of the protective effects of various antiulcer agents alone or in combination on indomethacin-induced gastric ulcers in rats. AB - The aim of this study which was structured with the objective of determination of the optimum protective therapy against the long term NSAID therapy-induced ulcers was to compare the gastro-protective effects of various antiulcer drugs (ranitidine, omeprazole, bismuth and misoprostol) alone or in combination with each other in different doses on indomethacin-induced gastric ulcers in rats. In this experimental study the protective effect of misoprostol (100 MUg/kg/day and 10 MUg/kg/day i.g.), omeprazole (5 mg/kg/day and 1.5 mg/kg/day i.p.), ranitidine (40 mg/kg/day and 10 mg/kg/day i.p.), bismuth (70 mg/kg/day and 15 mg/kg/day i.g.), combinations of misoprostol (10 MUg/kg/day i.g.) plus omeprazole (1.5mg/kg/day i.p.) and misoprostol (10 MUg/kg/day i.g.) plus ranitidine (10 mg/kg/day i.p.) are investigated on indomethacin (50 mg/kg/day s.c.) induced gastric ulcers. Half an hour before indomethacin administration, each group received the above treatment regimens for 5 days. After 5-day treatment, the rats were sacrificed and histopathological and hematological examinations were performed. The following regimens were found to be effective in the prevention of indomethacin-induced gastric lesions: 100 MUg/kg misoprostol, 10 MUg/kg misoprostol, 5mg/kg omeprazole, combination of 10 MUg/kg misoprostol plus 1.5 mg/kg omeprazole and 10 MUg/kg misoprostol plus 10 mg/kg ranitidine. The prevention rates achieved by these treatments were 71.4%, 50%, 47.6%, 52.4% and 50%, respectively. As a result of this study, misoprostol and omeprazol were found to be effective in protection against NSAID-induced gastric problems; while, ranitidine and bismuth were not. Also, the combinations of these agents were not found to have additive or synergistic effects. PMID- 21030228 TI - Gene silencing of the Lentinula edodes lcc1 gene by expression of a homologous inverted repeat sequence. AB - Lentinula edodes is one of the most important edible mushrooms, but no method for analyzing its molecular genetics has yet been established. RNA interference (RNAi) is a mechanism that inhibits expression of specific genes at the post transcriptional stage and has been used to analyze the genetics of several fungal species. RNAi was used to examine the expression of the laccase (EC 1.10.3.2) gene lcc1 of L. edodes, which encodes a lignin-degrading enzyme. Vector pChG' ivrL1 that expressed a 40 bp homologous inverted repeat sequence from lcc1 was constructed. This was transformed into L. edodes using the restriction enzyme mediated integration method (REMI). Lcc1 protein was not detected in two of 57 transformants (ivrL1#26, ivrL1#32) where the lcc1 transcription levels were suppressed. Thus, a 40 bp inverted repeat sequence expression vector suppressed expression of the target gene in L. edodes. Lcc1 downregulated transformants (ivrL1#32) did not form a thick aerial mycelium mat on agar medium. Electron microscopy showed hyphae of ivrL1#32 had many short branches with low mycelial density, a thin cell wall, and few fibrous layers as compared to the host strain. These morphological phenotypes would be caused by the absence of Lcc1, and that provides some clue to resolve the biological function of Lcc1 in L. edodes. Our results show that RNAi can be used for gene silencing in L. edodes. PMID- 21030229 TI - TAM receptor signaling and autoimmune disease. AB - The TAM receptor tyrosine kinases Tyro3, Axl, and Mer and their ligands Gas6 and Protein S are essential for the phagocytosis of apoptotic cells and membranes in the adult immune, nervous, and reproductive systems. Genetic studies indicate that this receptor-ligand system is central to apoptotic cell engulfment that is triggered by the 'eat-me' signal phosphatidylserine (PtdSer). At the same time, TAM signaling is normally activated by Toll-like receptor (TLR) and type I interferon signaling, as part of the innate inflammatory response in dendritic cells (DCs) and macrophages, where it inhibits this response. Deficiencies in TAM signaling result in human retinal dystrophies and may contribute to lupus and other human autoimmune diseases. PMID- 21030230 TI - Transcutaneous monitoring as a replacement for arterial PCO(2) monitoring during nocturnal non-invasive ventilation. AB - BACKGROUND: Continuous, non-invasive assessment of alveolar ventilation achieved by transcutaneous PCO(2) (PtcCO(2)) monitoring is clearly superior to intermittent, invasive blood gas analyses in patients receiving nocturnal non invasive positive pressure ventilation (NPPV), but the reliability and accuracy of PtcCO(2)-monitoring is still disputed. The present study was aimed at investigating the capability of modern PtcCO(2)-monitoring to reliably assess alveolar ventilation during nocturnal NPPV. METHODS: Capillary blood gas measurements (11pm, 2am, 5am and 7am) and 8 h of continuous PtcCO(2)-monitoring using three of the latest generation devices (SenTec Digital Monitor, Radiometer TCM4-TINA and Radiometer TOSCA500) were performed during polysomnography-proven sleep studies in 24 patients receiving NPPV (15 with COPD, 9 with restrictive disorders). RESULTS: The technical calibration drift for SenTec DM, TCM4-TINA and TOSCA500 was 0.1, -0.4 and -0.5 mmHg/h, respectively. Bland-Altman method comparison of PaCO(2)/drift-uncorrected PtcCO(2) revealed a mean bias (limits of agreement) of 1.0 (-4.7 to 6.7), -1.5 (-15.6 to 12.5) and 0.8 (-6.8 to 8.3) mmHg, respectively. Continuous overnight PtcCO(2)-monitoring detected variations in alveolar ventilation, with median ranges of 12.3 (10.7-14.5) mmHg for SenTec DM, 14.5 (12.5-17.0) mmHg for TCM4-TINA and 11.5 (11.0-13.0) mmHg for TOSCA500 (RM ANOVA, p < 0.001). The four capillary PaCO(2) values ranged by a median of 6.3 (4.7-9.7) mmHg. CONCLUSIONS: Modern PtcCO(2)-monitoring is reliable, accurate and robust. Since PtcCO(2)-monitoring is also non-invasive, does not disrupt sleep quality and provides a more complete picture of alveolar ventilation than intermittent capillary PaCO(2), PtcCO(2)-monitoring should become the preferred technique for assessing alveolar ventilation during nocturnal NPPV. TRIAL REGISTRATION: DRKS00000433 at http://apps.who.int/trialsearch/default.aspx. PMID- 21030231 TI - Increase in asthma and a high prevalence of bronchitis: results from a population study among adults in urban and rural Vietnam. AB - BACKGROUND: While a large amount of data about the epidemiology of asthma, COPD, chronic bronchitis and respiratory symptoms are available from developed countries, the information about these diseases in developing countries in south east Asia are scarce. AIM: Assess the prevalence of respiratory diseases and symptoms and their relation with demographic data including smoking habits among adults in rural and urban Vietnam. METHODS: A random sample of subjects aged 21 70 years were invited; 3008 subjects living in an inner city area of Hanoi and 4000 in a rural area of Bavi in northern Vietnam. An internationally used questionnaire was delivered by field workers to the study subjects. The questionnaire was completed by the subjects, or when necessary, by the field workers after reading the questions for the study participants. RESULTS: The response rate was 92% in Bavi and 70% in Hanoi. Of men in Bavi 67.8% (Hanoi 49.7%; p < 0.001) were smokers, while of women 4.2% were smokers in Hanoi (Bavi 1.2%; p < 0.001). The prevalence of ever asthma was in Hanoi 5.6% (Bavi 3.9%; p = 0.003) with no major gender difference. The most common symptom was longstanding cough (Hanoi 18.1%, Bavi 12.0%; p < 0.001) followed by sputum production, while the prevalence of symptoms common in asthma was considerably lower. Although the large difference in smoking habits, respiratory symptoms tended to be only slightly more common in men than women. Family history of asthma and chronic bronchitis, respectively, were strongly associated with both diseases. CONCLUSIONS: The prevalence of asthma in adults may have increased in both urban and rural Vietnam, as the few previous estimates have found 2% of adults having asthma. Half of men in Hanoi and two-thirds in Bavi were smokers versus a few percent of women in both areas. Bronchitic symptoms were common in both men and women. PMID- 21030232 TI - Excessive costs of COPD in ever-smokers. A longitudinal community study. AB - AIM: We aimed to estimate the societal treatment-related costs of COPD in hospital- and population-based subjects with spirometry defined COPD, relative to a control group. METHODS: 81 COPD cases and 132 controls without COPD were randomly recruited from a general population, as were 205 COPD patients from a hospital register. All participants were ever-smokers of at least 40 years of age, followed for 12 months. Data on comorbid conditions and spirometry were collected at baseline. Standardized telephone interviews every third month gave information on use of healthcare services and exacerbations of respiratory symptoms. RESULTS: The increased (excessive) median annual costs per case having stage II, stage III and stage IV COPD were ? (95% CI) 400 (105-695), 1918 (1268 2569) and 1870 (1031-2709), respectively, compared to the population-based controls. Costs increased with ?81 (95% CI 50-112) per exacerbation of respiratory symptoms and ?461 (95% CI 354-567) per comorbid condition. Excessive costs for hospital COPD patients were threefold that of the population-based COPD cases. CONCLUSION: The excessive treatment-related cost of COPD stage II+ in ever smokers of at least 40 years was estimated to ?105 million for Norway. Comorbidity was a dominant predictor of excessive cost in COPD. PMID- 21030233 TI - Germ cell sex determination: a collaboration between soma and germline. AB - Sex determination is regulated very differently in the soma vs. the germline, yet both processes are critical for the creation of the male and female gametes. In general, the soma plays an essential role in regulating sexual identity of the germline. However, in some species, such as Drosophila and mouse, the sex chromosome constitution of the germ cells makes an autonomous contribution to germline sexual development. Here we review how the soma and germline cooperate to determine germline sexual identity for some important model systems, the fly, the worm and the mouse, and discuss some of the implications of 'dual control' (soma plus germline) as compared to species where germline sex is dictated only by the surrounding soma. PMID- 21030235 TI - Autophagy for tissue homeostasis and neuroprotection. AB - Although autophagy has frequently been viewed as a cell death mechanism in the mammalian system, it is now considered as indispensable for the homeostasis of cells, tissues, and organisms. Basal or stress-induced autophagy plays essential and diverse roles in a variety of tissues, due to its cytoprotective properties. In this review, we briefly discuss the different homeostatic functions of autophagy that have been finely dissected in mammals through the generation and characterization of animal models with tissue-specific autophagic alterations. In addition, and given the importance of constitutive autophagy in neuronal tissues, we describe in more detail the specific roles of autophagy in the central nervous system (CNS). Finally, we discuss the contribution of autophagy malfunctions to the development of several common neurological disorders and the potential benefits of pharmacologically induced autophagy for the avoidance of neurodegeneration. PMID- 21030234 TI - Functional interactions between nucleoporins and chromatin. AB - As the gatekeepers of the eukaryotic cell nucleus, nuclear pore complexes (NPCs) mediate all molecular trafficking between the nucleoplasm and the cytoplasm. In recent years, transport-independent functions of NPC components, nucleoporins, have been identified including roles in chromatin organization and gene regulation. Here, we summarize our current view of the NPC as a dynamic hub for the integration of chromatin regulation and nuclear trafficking and discuss the functional interplay between nucleoporins and the nuclear genome. PMID- 21030236 TI - The ever-expanding list of HLA alleles: changing HLA nomenclature and its relevance to clinical transplantation. AB - Since the discovery of the HLA system 51 years ago, both the techniques for the detection of HLA antigens and the method of nomenclature for cataloguing them have changed dramatically. Initially serology was the sole technological tool available to describe the polymorphism of the class 1 and later the class 2 loci. Numbers were assigned to antigens as they were described and as serologic techniques that improved "subtypes" of the original antigens were described. With sequencing of HLA alleles, further polymorphisms were described, and it became evident that the degree of polymorphism was much greater than had hitherto been realized. Sequence differences were detected between alleles, which did not appear to provoke antibody responses but were clearly recognized by responding T cells. A new method of nomenclature was devised, which assigned 2 sets of numbers to each allele. The first 2 numbers indicated the serologic group to which the allele belonged, whereas the second set of 2 numbers was assigned in a numerical progression as each new allele was described. In addition, letters were introduced at the end of each allele where they were known to be nonexpressed or have low levels of cell expression. The limitation of this system is that it only caters for 99 alleles in each serologic group, and this has now been exceeded in some cases. The World Health Organization Nomenclature Committee for factors of the HLA system introduced a modification of the current nomenclature in April 2010 which uses colons to separate the numbers that has the effect of delimiting the number of alleles, which can be assigned to each serologic group. Due to the extensive polymorphism of the HLA genes, sequencing frequently results in ambiguous combinations of alleles and also "strings" of possible alleles due to polymorphisms in nonsequenced gene locations. The reporting in such instances has been simplified to some extent by the introduction of a lettering system to indicate a particular "string." The nomenclature of the HLA system can be confusing to those outside the HLA scientific community. It is important, however, that physicians, particularly those involved in transplantation, have a working knowledge of the nomenclature. It is important in solid organ transplantation in terms of interpreting the relevance of HLA antibodies in cases where there are clear demonstrations in patients of allele-specific antibodies. It is critical in hematopoietic stem cell transplantation where allele level matching is imperative and where decisions have to be made regarding the likelihood of possible sequence mismatches and the clinical relevance of nonexpression or low expression of HLA allelic products. PMID- 21030237 TI - Reductive determination of hydrogen peroxide with MWCNTs-Pd nanoparticles on a modified glassy carbon electrode. AB - This paper introduces the use of multi walled carbon nanotubes (MWCNTs) with palladium (Pd) nanoparticles in the electrocatalytic reduction of hydrogen peroxide (H(2)O(2)). We have developed and characterized a biosensor for H(2)O(2) based on Nafion((r)) coated MWCNTs-Pd nanoparticles on a glassy carbon electrode (GCE). The Nafion((r))/MWCNTs-Pd/GCE electrode was easily prepared in a rapid and simple procedure, and its application improves sensitive determination of H(2)O(2). Characterization of the MWCNTs-Pd nanoparticle film was performed with transmission electron microscopy (TEM), Raman, and X-ray photoelectron spectroscopy (XPS). Cyclic voltammetry (CV) and amperometry (at an applied potential of -0.2V) measurements were used to study and optimize performance of the resulting peroxide biosensor. The proposed H(2)O(2) biosensor exhibited a wide linear range from 1.0 MUM to 10 mM and a low detection limit of 0.3 MUM (S/N=3), with a fast response time within 10s. Therefore, this biosensor could be a good candidate for H(2)O(2) analysis. PMID- 21030238 TI - Using silicon nanowire devices to detect adenosine triphosphate liberated from electrically stimulated HeLa cells. AB - In this study, we used a biosensor chip featuring Abl tyrosine kinase-modified silicon nanowire field-effect transistors (SiNW-FETs) to detect adenosine triphosphate (ATP) liberated from HeLa cells that had been electrically stimulated. Cells that are cultured in high-ionic-strength media or buffer environments usually undermine the sensitivity and selectively of SiNW-FET-based sensors. Therefore, we first examined the performance of the biosensor chip incorporating the SiNW-FETs in both low- and high-ionic-strength buffer solutions. Next, we stimulated, using a sinusoidal wave (1.0 V, 50 Hz, 10 min), HeLa cells that had been cultured on a cell-culture chip featuring interdigitated electrodes. The extracellular ATP concentration increased by ca. 18.4-fold after electrical stimulation. Finally, we detected the presence of extracellular ATP after removing a small amount of buffer solution from the cell-cultured chip and introducing it into the biosensor chip. PMID- 21030240 TI - Conductive polymer-based sensors for biomedical applications. AB - A class of organic polymers, known as conducting polymers (CPs), has become increasingly popular due to its unique electrical and optical properties. Material characteristics of CPs are similar to those of some metals and inorganic semiconductors, while retaining polymer properties such as flexibility, and ease of processing and synthesis, generally associated with conventional polymers. Owing to these characteristics, research efforts in CPs have gained significant traction to produce several types of CPs since its discovery four decades ago. CPs are often categorised into different types based on the type of electric charges (e.g., delocalized pi electrons, ions, or conductive nanomaterials) responsible for conduction. Several CPs are known to interact with biological samples while maintaining good biocompatibility and hence, they qualify as interesting candidates for use in a numerous biological and medical applications. In this paper, we focus on CP-based sensor elements and the state-of-art of CP based sensing devices that have potential applications as tools in clinical diagnosis and surgical interventions. Representative applications of CP-based sensors (electrochemical biosensor, tactile sensing 'skins', and thermal sensors) are briefly discussed. Finally, some of the key issues related to CP-based sensors are highlighted. PMID- 21030239 TI - Ultrasensitive electrochemical aptasensor for thrombin based on the amplification of aptamer-AuNPs-HRP conjugates. AB - Successful development of an ultrasensitive and highly specific electrochemical aptasensor for thrombin based on amplification of aptamer-gold nanoparticles horseradish peroxidase (aptamer-AuNPs-HRP) conjugates was reported. In this electrochemical protocol, aptamer1 (Apt1) was immobilized on core/shell Fe(3)O(4)/Au magnetic nanoparticles (AuMNPs) and served as capture probe. Aptamer2 (Apt2) was dual labeled with AuNPs and HRP and used as detection probe. In the presence of thrombin, the sandwich format of AuMNPs-Apt1/thrombin/Apt2 AuNPs-HRP was fabricated. Remarkable signal amplification was realized by taking the advantage of AuNPs and catalytic reactions of HRP. Other proteins, such as human serum albumin, lysozyme, fibrinogen, and IgG did not show significant interference with the assay for thrombin. Linear response to thrombin concentration in the range of 0.1-60 pM and lower detection limit down to 30 fM (S/N=3) was obtained with the proposed method. This electrochemical aptasensor is simple, rapid (the whole detection period for a thrombin sample is less than 35 min), sensitive and highly specific, it shows promising potential in protein detection and disease diagnosis. PMID- 21030241 TI - Polysilicon wire glucose sensor highly immune to interference. AB - This study investigated the interference elimination ability of a glucose sensor made of polysilicon wire (PSW) with a surface modified by 3 aminopropyltriethoxysilane mixed with polydimethylsiloxane-treated hydrophobic fumed silica nanoparticles plus ultra-violet illumination (gamma-APTES+NPs+UV). Glucose sensing of the PSW sensor in the presence of five common interferences such as ascorbic acid (AA), uric acid (UA), acetaminophen (AP), L-cysteine (Lys), and citric acid (CA) was performed. We found that the disturbance caused by the interferences was low for interference-to-glucose concentration ratios up to 600:1 if the PSW surface is modified with gamma-APTES+NPs+UV. The outstanding interference immunity of this PSW glucose sensor is believed to be mainly due to the fact that it is a dry-type sensor and the extremely low leakage of the gamma APTES+NPs membrane which allows the PSW to show three orders of magnitude lower leakage current than with the gamma-APTES membrane only. In addition to its excellent interference immunity, the PSW glucose sensor with a line width of 100 nm also exhibits a wide linear detection range, an ultra-high sensitivity, an ultra low detection limit, and it can be reused more than a thousand times without much sensitivity degradation. PMID- 21030242 TI - Label-free and sensitive electrogenerated chemiluminescence aptasensor for the determination of lysozyme. AB - A novel label-free electrogenerated chemiluminescence (ECL) aptasensor for the determination of lysozyme is designed employing lysozyme binding aptamer (LBA) as molecular recognition element for lysozyme as a model analyte and Ru(bpy)(3)(2+) as an ECL signal compound. This ECL aptasensor was fabricated by self-assembling the thiolated LBA onto the surface of a gold electrode. Using this aptasensor, sensitive quantitative detection of lysozyme is realized on basis of the competition of lysozyme with Ru(bpy)(3)(2+) cation for the binding sites of LBA. In the presence of lysozyme, the aptamer sequence prefers to form the LBA lysozyme complex, the less negative environment allows Ru(bpy)(3)(2+) cations to be less bound electrostatically to the LBAs on the electrode surface, in conjunction with the generation of a decreased ECL signal. The integrated ECL intensity versus the concentration of lysozyme was linear in the range from 6.4*10(-10) M to 6.4*10(-7) M. The detection limit was 1.2*10(-10) M. This work demonstrates that using the competition of target protein with an ECL signal compound Ru(bpy)(3)(2+) for binding sites of special aptamer confined on the electrode is promising approach for the design of label-free ECL aptasensors for the determination of proteins. PMID- 21030243 TI - How to obtain labeled proteins and what to do with them. AB - We review new and established methods for the chemical modification of proteins in living cells and highlight recent applications. The review focuses on tag mediated protein labeling methods, such as the tetracysteine tag and SNAP-tag, and new developments in this field such as intracellular labeling with lipoic acid ligase. Recent promising advances in the incorporation of unnatural amino acids into proteins are also briefly discussed. We describe new tools using tag mediated labeling methods including the super-resolution microscopy of tagged proteins, the study of the interactions of proteins and protein domains, the subcellular targeting of synthetic ion sensors, and the generation of new semisynthetic metabolite sensors. We conclude with a view on necessary future developments, with one example being the selective labeling of non-tagged, native proteins in complex protein mixtures. PMID- 21030244 TI - Biocatalysis--key to sustainable industrial chemistry. AB - The ongoing trends to process improvements, cost reductions and increasing quality, safety, health and environment requirements of industrial chemical transformations have strengthened the translation of global biocatalysis research work into industrial applications. One focus has been on biocatalytic single-step reactions with one or two substrates, the identification of bottlenecks and molecular as well as engineering approaches to overcome these bottlenecks. Robust industrial procedures have been established along classes of biocatalytic single step reactions. Multi-step reactions and multi-component reactions (MCRs) enable a bottom-up approach with biocatalytic reactions working together in one compartment and recations hindering each other within different compartments or steps. The understanding of the catalytic functions of known and new enzymes is key for the development of new sustainable chemical transformations. PMID- 21030245 TI - Biologically active secondary metabolites from marine cyanobacteria. AB - Marine cyanobacteria are a rich source of complex bioactive secondary metabolites which derive from mixed biosynthetic pathways. Recently, several marine cyanobacterial natural products have garnered much attention due to their intriguing structures and exciting anti-proliferative or cancer cell toxic activities. Several other recently discovered secondary metabolites exhibit insightful neurotoxic activities whereas others are showing pronounced anti inflammatory activity. A number of anti-infective compounds displaying activity against neglected diseases have also been identified, which include viridamides A and B, gallinamide A, dragonamide E, and the almiramides. PMID- 21030246 TI - Trigger point therapy and plantar heel pain: A case report. AB - The cause of plantar heel pain and fasciitis has continued to be a diagnostic challenge even though it is one of the most common musculoskeletal disorders of the foot and ankle. The subject has evoked strong emotions and sparked intense debate regarding the likely causes and effective treatment options. Myofascial trigger point as a treatment option for plantar heel pain and fasciitis has been inconspicuous. The full extent of its significance and potential is largely unexplored in podiatric literature and medicine. Myofascial trigger point may offer an alternative explanation of the etiology of plantar heel pain and fasciitis. PMID- 21030247 TI - Bridging cell wall biosynthesis and bacterial morphogenesis. AB - The bacterial cell wall is a complex three-dimensional structure that protects the cell from environmental stress and ensures its shape. The biosynthesis of its main component, the peptidoglycan, involves the coordination of activities of proteins present in the cytoplasm, the membrane, and the periplasm, some of which also interact with the bacterial cytoskeleton. The sheer complexity of the cell wall elongation process, which is the main focus of this review, has created a significant challenge for the study of the macromolecular interactions that regulate peptidoglycan biosynthesis. The availability of new structural and biochemical data on a number of components of peptidoglycan assembly machineries, including a complex between MreB and RodZ as well as structures of penicillin binding proteins (PBPs) from a number of pathogenic species, now provide novel insight into the underpinnings of an intricate molecular machinery. PMID- 21030248 TI - Anaerobic digestion of slaughterhouse waste: main process limitations and microbial community interactions. AB - Fresh pig/cattle slaughterhouse waste mixtures, with different lipid-protein ratios, were characterized and their anaerobic biodegradability assessed in batch tests. The resultant methane potentials were high (270-300 L(CH4) kg(-1)(COD)) making them interesting substrates for the anaerobic digestion process. However, when increasing substrate concentrations in consecutive batch tests, up to 15 g(COD) kg(-1), a clear inhibitory process was monitored. Despite the reported severe inhibition, related to lipid content, the system was able to recover activity and successfully degrade the substrate. Furthermore, 16SrRNA gene-based DGGE results showed an enrichment of specialized microbial populations, such as beta-oxidizing/proteolitic bacteria (Syntrophomonas sp., Coprothermobacter sp. and Anaerobaculum sp.), and syntrophic methanogens (Methanosarcina sp.). Consequently, the lipid concentration of substrate and the structure of the microbial community are the main limiting factors for a successful anaerobic treatment of fresh slaughterhouse waste. PMID- 21030249 TI - A pilot study on the regeneration of ferrous chelate complex in NOx scrubber solution by a biofilm electrode reactor. AB - A chemical absorption-biological reduction integrated process has been proposed for the removal of nitrogen oxides (NO(x)) from flue gases. In this study, we report a new approach using biofilm electrode reactor (BER) to regenerate Fe(II)EDTA via simultaneously reducing Fe(II)EDTA-NO and Fe(III)EDTA in NO(x) scrubber solution. Biofilm formed on the surface of the cathode was confirmed by Environmental Scan Electro-Microscope. Experimental results demonstrated that it was effective and feasible to utilize the BER to promote the reduction of Fe(II)EDTA-NO and Fe(III)EDTA simultaneously. The reduction efficiency of Fe(II)EDTA-NO and Fe(III)EDTA was up to 85% and 78%, respectively when the BER was continuously operated with electricity current at 30 mA. The absence of electricity induced an immediate decrease in reduction efficiency, indicating that the bio-regeneration of ferrous chelate complex was electrochemically accelerated. The present approach is considered advantageous for the enhanced bio reduction in the NO(x) scrubber solution. PMID- 21030250 TI - qRT-PCR quantification of the biological control agent Trichoderma harzianum in peat and compost-based growing media. AB - To ensure proper use of Trichoderma harzianum in agriculture, accurate data must be obtained in population monitoring. The effectiveness of qRT-PCR to quantify T. harzianum in different growing media was compared to the commonly used techniques of colony counting and qPCR. Results showed that plate counting and qPCR offered similar T. harzianum quantification patterns of an initial rapid increase in fungal population that decreased over time. However, data from qRT-PCR showed a population curve of active T. harzianum with a delayed onset of initial growth which then increased throughout the experiment. Results demonstrated that T. harzianum can successfully grow in these media and that qRT-PCR can offer a more distinct representation of active T. harzianum populations. Additionally, compost amended with T. harzianum exhibited a lower Fusarium oxysporum infection rate (67%) and lower percentage of fresh weight loss (11%) in comparison to amended peat (90% infection rate, 23% fresh weight loss). PMID- 21030251 TI - Monitoring Rhodotorula glutinis CCMI 145 physiological response and oil production growing on xylose and glucose using multi-parameter flow cytometry. AB - Flow cytometry was used to monitor the lipid content, viability and intrinsic light scatter properties of Rhodotorula glutinis CCMI 145 cells growing on batch cultures using xylose and glucose as carbon sources. The highest lipid content was observed for cells grown on glucose, at the end of the exponential phase (17.8% w/w). The proportion of cells stained with PI attaining 77% at the end of the glucose growth. Cells growing on xylose produced a maximum lipid content of 10.6% (w/w), at the stationary phase. An increase in the proportion of cells stained with PI was observed, reaching 29% at the end of xylose growth. Changes in the side and forward light scatter detected during the yeast batch cultures supported that R. glutinis cells grown on glucose experienced harsher conditions, resulting in a high level of cytoplasmic membrane damage, which did not occur when R. glutinis cells grew on xylose. PMID- 21030252 TI - Differences and dynamic changes in the cell surface properties of three Pseudomonas aeruginosa strains isolated from petroleum-polluted soil as a response to various carbon sources and the external addition of rhamnolipids. AB - Three Pseudomonas aeruginosa strains isolated from petroleum-polluted soil were the subject of studies concerning changes in cell surface properties. Fundamentally different reactions could be observed for each of the studied strains after a cultivation on various carbon sources. The experiments carried out during the logarithmic growth phase showed, that the changes in the cell surface hydrophobocity values were dynamic and substrate dependant. An external addition of rhamnolipids to the tested systems resulted in further shifts in the CSH values. All of the strains displayed miscellaneous phenotypic properties during MATH, sedimentation profile, Zeta potential and surface tension measurements. The obtained results lead to a conclusion, that the presence of rhamnolipids seems to be the key factor to this phenomenon, as all of the studied strains exhibited the ability to produce this biosurfactant in a different degree. PMID- 21030253 TI - The characteristics and enzyme activities of 4-chlorophenol biodegradation by Fusarium sp. AB - The effects of pH, temperature and sucrose addition on biodegradative capacity of Fusarium sp. HJ01 for 4-chlorophenol (4-CP) were examined, the property of dioxygenases produced by Fusarium sp. HJ01 during 4-CP degradation was investigated. The results show that Fusarium sp. HJ01 has a high capacity on degrading 4-CP in solution. The optimum values of pH, sucrose concentration and temperature are pH 7,1 g/L and 30 degrees C, respectively. The strain can produce chlorocatechol 1,2-dioxygenase (CC12O) and chlorocatechol 2,3-dioxygenase (CC23O), which show the highest activities when 4-CP is used as the sole carbon source and energy, and the optimal values of pH and temperature are pH 7 and 50 degrees C for CC12O as well as pH 8 and 60 degrees C for CC23O. The kinetics of enzyme-catalyzed reactions accord with the Michaelis-Menten equation. To our knowledge, this is the first study on biodegradation of 4-CP by Fusarium sp. HJ01. PMID- 21030254 TI - Spiroimidazolidinone NPC1L1 inhibitors. Part 2: structure-activity studies and in vivo efficacy. AB - Ezetimibe (Zetia(r)), a cholesterol-absorption inhibitor (CAI) approved by the FDA for the treatment of hypercholesterolemia, is believed to target the intestine protein Niemann-Pick C1-Like 1 (NPC1L1) or its pathway. A spiroimidazolidinone NPC1L1 inhibitor identified by virtual screening showed moderate binding activity but was not efficacious in an in vivo rodent model of cholesterol absorption. Synthesis of analogs established the structure-activity relationships for binding activity, and resulted in compounds with in vivo efficacy, including 24, which inhibited plasma cholesterol absorption by 67% in the mouse, thereby providing proof-of-concept that non-beta-lactams can be effective CAIs. PMID- 21030255 TI - Synthesis, biological evaluation and radiolabelling by 18F-fluoroarylation of a dopamine D3-selective ligand as prospective imaging probe for PET. AB - Radical (18)F-fluoroarylation with fluorine-18-labelled arenediazonium chlorides has been successfully applied to the radiochemical synthesis of the dopamine D(3) selective ligand SH 317 ([(18)F]8). SH 317 has been evaluated as a new PET ligand candidate by in vivo experiments. PMID- 21030256 TI - Trifluoromethylphenyl as P2 for ketoamide-based cathepsin S inhibitors. AB - The trifluoromethylphenyl P2 motif from previously reported heteroarylnitrile series has been successfully applied for the design and synthesis of highly potent novel ketoamide-based cathepsin S inhibitors. The key in this process is the change of the torsion angle between the P2 phenyl ring and the attached secondary amide by adding a small Cl, F, or Me group at the 2-position. PMID- 21030257 TI - A novel small-molecule inhibitor of IL-6 signalling. AB - A small library of pyrrolidinesulphonylaryl molecules has been synthesized via an efficient 4-step route, and members evaluated for their ability to inhibit IL-6 signalling. One molecule (6a) was found to have promising activity against IL 6/STAT3 signalling at the low micromolar level, and to selectively inhibit phosphorylation of STAT3 (but not STAT1) in IL-6 stimulated MDA-MB-231 breast cancer and HeLa cell lines. It was also selectively cytostatic in MDA-MB-231 (STAT3-dependent) versus A4 (STAT3-null) cells suggesting STAT3-specific inhibitory properties. PMID- 21030258 TI - Optimal reconstruction of the bony defect after frontotemporal craniotomy with hydroxyapatite cement. AB - Numerous procedures have been reported for reconstruction of the bony defect around the sphenoid ridge after a frontotemporal craniotomy. However, it is still often difficult to restore the defect because of the complex curvature. Here we describe a simple cranial reconstruction method using hydroxyapatite cement and gelatin sponges. This procedure has been used on six patients, and satisfactory reconstruction was confirmed in all with postoperative three-dimensional CT scans. Using this technique, the bony defect was completely reconstructed with an appropriate thickness and curvature. PMID- 21030259 TI - Fourth-ventricular immature teratoma. AB - Teratomas account for 3% of all childhood tumors. This group of non-germinomatous germ cell tumors exhibit cellular and structural characteristics associated with the three germ layers. The immature cells can differentiate into more malignant neoplasms. We report the presentation and management of a 4-year-old girl with an immature teratoma of the fourth ventricle. The outcome of this intracranial immature teratoma was poor, due to the patient's age, the extensive lesion at presentation and the grade of the tumor. PMID- 21030260 TI - Postoperative paralysis following posterior decompression with instrumented fusion for thoracic myelopathy caused by ossification of the posterior longitudinal ligament. AB - A 60-year-old man presented with thoracic myelopathy due to ossification of the posterior longitudinal ligament (OPLL). His spinal cord was severely impinged anteriorly by a beak-type OPLL and posteriorly by ossification of the ligamentum flavum at T4/5. He underwent surgical posterior decompression with instrumented fusion (PDF). Immediately after surgery, he developed a Brown-Sequard-type paralysis, which spontaneously resolved without requiring the addition of OPLL extirpation. This example highlights that the risk of postoperative neurological deterioration cannot be eliminated even when PDF is selected as the surgical procedure for thoracic OPLL, especially in instances in which the spinal cord is severely compressed. PMID- 21030261 TI - Divergent pathways lead to ESCRT-III-catalyzed membrane fission. AB - Endosomal sorting complexes required for transport (ESCRT) have been implicated in topologically similar but diverse cellular and pathological processes including multivesicular body (MVB) biogenesis, cytokinesis and enveloped virus budding. Although receptor sorting at the endosomal membrane producing MVBs employs the regulated assembly of ESCRT-0 followed by ESCRT-I, -II, -III and the vacuolar protein sorting (VPS)4 complex, other ESCRT-catalyzed processes require only a subset of complexes which commonly includes ESCRT-III and VPS4. Recent progress has shed light on the pathway of ESCRT assembly and highlights the separation of tasks of different ESCRT complexes and associated partners. The emerging picture suggests that among all ESCRT-catalyzed processes, divergent pathways lead to ESCRT-III assembly within the neck of a budding structure catalyzing membrane fission. PMID- 21030262 TI - Activation mechanism for N-nitroso-N-methylbutylamine mutagenicity by radical species. AB - N-Nitrosodialkylamines are known to be potent indirect-acting mutagens/carcinogens, which are activated by cytochrome P450. The reaction product of N-nitroso-N-methylbutylamine (NMB) with modified Fenton's reagent supplemented with copper salt (Fe2(+)-Cu2(+)-H2O2) was reported to be mutagenic in Salmonella typhimurium TA1535 without S9 mix. In this study, the NMB activation mechanism was investigated by ESR spectroscopy with radical trapping agents to detect radical species and also by observing changes in mutagenic potency with a Salmonella strain in the Ames assay in the presence of radical trapping agents. In ESR spectroscopy experiments, the hydroxyl radical generated from the modified Fenton's reagent was detected using the hydroxyl radical trapping agent 5,5-dimethyl-1-pyrroline N-oxide (DMPO). Since the amount of the DMPO-OH adduct decreased with the addition of NMB, hydroxyl radical was presumed to react with NMB followed by the generation of nitric oxide (NO), which was detected as CarboxyPTI through reaction with 2-(4-carboxyphenyl)-4,4,5,5 tetramethylimidazoline-1-oxyl 3-oxide (CarboxyPTIO). The mutagenicity of the reaction extract decreased following the addition of DMPO or CarboxyPTIO. Furthermore, the mutagenicity of the reaction product in the presence of DMPO was enhanced by the addition of NO. The reaction product from NMB with Fe2(+)-Cu2(+) NO in the absence of H2O2 was mutagenic, and this activity increased with the introduction of additional NO. These findings suggest that hydroxyl radical takes part in the generation of NO from NMB and that NO plays an important role in NMB activation in the presence of Fe2(+) and Cu2(+). PMID- 21030263 TI - 1,3-Diphenyl-1H-pyrazole derivatives as a new series of potent PPARgamma partial agonists. AB - A new series of PPARgamma partial agonists, 1,3-diphenyl-1H-pyrazole derivatives, were identified using an improved virtual screening scheme combining ligand centric and receptor-centric methods. An in vitro assay confirmed the nanomolar binding affinity of 1,3-diphenyl-1H-pyrazole derivatives such as SP3415. We also characterized the competitive antagonism of SP3415 against rosiglitazone at micromolar concentrations. They showed a PPARgamma partial agonistic activity similar to that of a known PPARgamma drug, pioglitazone, in a cell-based transactivation assay. Furthermore, the structure-activity relationships of the pyrazole derivatives were investigated through comparative molecular field analysis and binding mode analysis, which provided new insight concerning their partial agonistic effect on PPARgamma. PMID- 21030264 TI - Polarization effects in 4Pi microscopy. AB - The effects of different apodization conditions and polarization distributions on imaging in 4Pi microscopy are discussed. Performance parameters are derived that allow the different implementations to be compared. 4Pi microscopy is mainly used because of its superior axial imaging performance, but it is shown that transverse resolution is also improved in the 4Pi geometry, by as much as 25% compared with focusing by a single aplanatic lens. Compared with plane-polarized illumination in a 4Pi aplanatic system, transverse resolution in the 4Pi mode can also be increased by about 18%, using radially polarized illumination, but at the expense of axial resolution. The electric energy density at the focus for a given power input can be increased using electric dipole polarization, which is relevant for atomic physics experiments such as laser trapping and cooling. PMID- 21030265 TI - Zoledronate, ibandronate and clodronate enhance osteoblast differentiation in a dose dependent manner--a quantitative in vitro gene expression analysis of Dlx5, Runx2, OCN, MSX1 and MSX2. AB - Bisphosphonates are widely used in the clinical treatment of bone diseases with increased bone resorption. In terms of side effects, they are known to be associated with osteonecrosis of the jaw (BONJ). There are two groups of bisphosphonates: the nitrogen-containing bisphosphonates, e.g. zoledronate and ibandronate, and the non-nitrogen-containing bisphosphonates, e.g. clodronate. Their impact on bone metabolism seems to differ. The objective of this study was to compare the osteogenic differentiation potency of these two pharmacologic groups. Human osteoblasts were stimulated with zoledronate and ibandronate at concentrations of 5*10(-5) M, 5*10(-6) M and 5*10(-7) M over the experimental periods of 1, 2, 5, 10 and 14 days. Clodronate was applied with concentrations of 5*10(-3), 5*10(-5) M and 5*10(-6) M. At each time point, the cells were dissolved, the mRNA extracted, and the gene expression level of the osteoblast specific differentiation markers of the homeobox transcription factors MSX1 and MSX2, the distal-less homeobox 5 (Dlx5), the Runt-related transcription factor 2 (Runx2/CBF1a) and osteocalcin (OCN) were quantified by Real-Time PCR. The gene expression was compared to an unstimulated osteoblast cell culture as control. The results showed a significant difference between the nitrogen-containing and the non-nitrogen-containing bisphosphonates. Zoledronate and ibandronate at concentrations of 5*10(-5) M enhanced the gene expression of all differentiation markers by several hundred folds compared to unstimulated control after 10 days, whereas clodronate had less influence on gene expression, even at higher concentrations of 5*10(-3) M. Lower concentrations of zoledronate and ibandronate, however, led to a decreased gene expression. These data confirm the results of other studies which have shown the osteogenic stimulus on osteoblasts in a dose dependent manner. The nitrogen-containing bisphosphonates appear to enhance bone density by stimulation of osteoblast differentiation. Non-nitrogen containing bisphosphonates seem to have less influence on osteoblast differentiation. PMID- 21030266 TI - Morphometric analysis - Cone beam computed tomography to predict bone quality and quantity. AB - AIM: Modified quantitative computed tomography is a method used to predict bone quality and quantify the bone mass of the jaw. The aim of this study was to determine whether bone quantity or quality was detected by cone beam computed tomography (CBCT) combined with image analysis. MATERIALS AND PROCEDURES: Different measurements recorded on two phantoms (Siemens phantom, Comac phantom) were evaluated on images taken with the Somatom VolumeZoom (Siemens Medical Solutions, Erlangen, Germany) and the NewTom 9000 (NIM s.r.l., Verona, Italy) in order to calculate a calibration curve. The spatial relationships of six sample cylinders and the repositioning from four pig skull halves relative to adjacent defined anatomical structures were assessed by means of three-dimensional visualization software. RESULTS: The calibration curves for computer tomography (CT) and cone beam computer tomography (CBCT) using the Siemens phantom showed linear correlation in both modalities between the Hounsfield Units (HU) and bone morphology. A correction factor for CBCT was calculated. Exact information about the micromorphology of the bone cylinders was only available using of micro computer tomography. CONCLUSION: Cone-beam computer tomography is a suitable choice for analysing bone mass, but, it does not give any information about bone quality. PMID- 21030268 TI - Interleukin-10-1082 promoter polymorphism and ischemic stroke risk in a South Indian population. AB - Within the past few years there has been increasing evidence that the genetic variation in the genes coding pro- and anti-inflammatory markers may play an important role in the pathogenesis of various human diseases, including stroke. The aim of the study was to evaluate the association of Interleukin-10 (IL-10) 1082 G/A, promoter polymorphism (rs1800896) with ischemic stroke in a South Indian population from Andhra Pradesh. In this study 480 ischemic stroke patients and 470 age and sex matched healthy controls were included. The ischemic stroke patients were classified according to TOAST classification. The region of interest in the IL-10 gene was amplified by polymerase chain reaction with the use of allele specific oligonucleotide primers flanking the polymorphic region. Association between genotypes and stroke was examined by Odds Ratio (OR) with 95% confidence interval (CI) and Chi-square analysis. Significant difference was observed between the patients and healthy controls, in genotypic distribution as well as allelic frequency (p<0.05). Multiple logistic regression analysis with forward stepwise selection using the potential confounders (sex, age, diabetes, hypertension, smoking and alcoholism) and IL-10 gene variant revealed that -1082 G/A polymorphism in the promoter region of IL-10 gene is significantly [adjusted OR=2.26; 95% C.I. (1.24-4.15), p<0.001] associated with ischemic stroke in the South Indian population from Andhra Pradesh. We found significant association of this polymorphism with stroke of undetermined etiology (p<0.001). Moreover, hypertensive and diabetic individuals bearing A allele of IL-10 gene in high frequency were found to be more predisposed to stroke. PMID- 21030267 TI - Surgical treatment of lung cancer in the octogenarians: results of a nationwide audit. AB - OBJECTIVE: The elderly is a fast-growing segment of the population and the number of oncogeriatric patients with lung cancer is expected to increase. The purpose of this study was to overview surgical habits for lung cancer in octogenarians. METHODS: We used EPITHOR((r)), the French national thoracic database, created in 2002 and including more than 135000 procedures from 93 institutions. We collected prospectively data concerning 622 patients 80 years or older, and 16461 patients younger than 80 years with lung cancer from 1 January 2004 to 31 December 2008. We compared patients' characteristics, lung-cancer presentation, and surgical treatment between these two groups. RESULTS: Patients' characteristics analysis: the distribution by gender, body mass index, and forced expiratory volume was comparable for the two groups. American Society of Anesthesiologists (ASA) score (ASA 1 and 2: 59%, n=363 vs 71%, n=11543, p<0.0001) and performance status (PS) were worse for older patients (PS 0 and 1: 86%, n=470 vs 89%, n=12685, p<0.0001). Mean age (82.0, confidence interval (CI) 95% (81.9; 82.2)) and sex ratio (2.51, n=445 males) were stable for octogenarians across 5 years. Lung-cancer presentation analysis: in the elderly, stages I and II were of 71% (n=361) versus 66% (n=8735) in the younger group (p=0.001). Surgical treatment analysis: resections in octogenarians were pneumonectomy 10% (n=62) versus 15% (n=2409) for patients under 80 years, lobectomy 67% (n=415) versus 65% (n=10734), bilobectomy 4% (n=25) versus 5% (n=809), sub-lobar resection 11% (n=70) versus 8% (n=1355) (p=0.034). They underwent video-assisted thoracic surgery in 7% (n=43) versus 6% (n=917) (p=0.034). No lymph node dissection was more frequent in patients 80 years or older (8%, n=45) than in younger patients (5%, n=738) (p=0.0004). CONCLUSION: Taken as a whole, octogenarians underwent more sub-lobar resections and less mediastinal lymph node dissections than younger patients. Effective management of lung cancer in older patients should be tailed to individual needs. Surgical treatment should not be denied on chronological age alone anymore. PMID- 21030269 TI - Transcription factor Ap-1 mediates proangiogenic MIF expression in human endothelial cells exposed to Angiotensin II. AB - Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine associated with the atherosclerotic process and atherosclerotic plaque stability. MIF was shown to be highly expressed in advanced atherosclerotic lesions. Neutralizing MIF with a blocking antibody induced a regression of established atherosclerotic lesions. In this study, we investigated the mechanism underlying the proangiogenic effect of MIF in human umbilical vein endothelial cells (HUVECs). We showed that MIF induced the expression of angiogenesis-related genes in HUVECs. We also showed that MIF induced tube formation of HUVECs in vitro and in vivo. Angiotensin II (Ang II) could specifically up-regulate MIF expression in HUVECs. Using a luciferase reporter assay, we demonstrated that the AP-1 response element in the 5'-UTR of the MIF gene played a role in Ang II-induced MIF expression. Small hairpin RNA (shRNA) targeting c-Jun, a component of AP-1, and the AP-1 inhibitor CHX both efficiently inhibited MIF expression. The consistent result of electrophoretic mobility shift assay (EMSA) showed that Ang II specifically increased AP-1 activation in HUVECs. Our results suggest that AP-1 mediates Ang II-induced MIF expression which contributes to atherosclerotic plaque destabilization in human endothelial cells. PMID- 21030270 TI - The influence of the muscle fiber pennation angle and innervation zone on the identification of neuromuscular fatigue during cycle ergometry. AB - The purpose of the present investigation was to compare the electromyographic (EMG) responses and the estimated physical working capacity at the fatigue threshold (PWC(FT)) values recorded from electrode arrangements placed: (1) parallel to the muscle fiber pennation angle (MFPA), (2) parallel to the long axis of the femur, and (3) over the innervation zone (IZ) during incremental cycle ergometry. Thirteen college-aged males and females (mean age +/- SD=22.4 +/ 3.4 years) performed an incremental test to exhaustion on a cycle ergometer. A linear electrode array was utilized to determine the MFPA and location of the IZ of the vastus lateralis (VL). For determination of the PWC(FT) values, EMG signals were recorded from three bipolar electrode arrangements at different locations over the VL. The results of a one-way repeated measures ANOVA indicated there were no significant (p<0.05) mean differences in PWC(FT) values among the electrode arrangements (parallel to the MFPA=190 +/- 36 W; parallel to the long axis of the femur=194 +/- 40 W; and over the IZ=199 +/- 51 W) or the EMG amplitude and MPF values at the common power outputs. There were also significant correlations (r=0.75-0.91) among the three electrode arrangements for PWC(FT) values. These findings suggested that the PWC(FT), like absolute EMG amplitude and MPF, is robust to the influence of electrode placement over the IZ as well as the orientation with respect to the MFPA during cycle ergometry. PMID- 21030271 TI - Mesenchymal stem cell conditioned media attenuates in vitro and ex vivo myocardial reperfusion injury. AB - BACKGROUND: Previous studies have suggested that implantation of mesenchymal stem cells (MSC) or their conditioned media (MSC CM) improves heart function after myocardial infarction. We sought to determine whether MSC and MSC CM added at the onset of reperfusion attenuates myocardial reperfusion injury. METHODS: Rat MSC and neonatal rat cardiomyocytes (NRC) were isolated and cultured separately. NRC were subjected to simulated in vitro ischemia/reperfusion (I/R). At the onset of reperfusion, NRC received either fresh medium (control group) or one of the following treatments: MSC in fresh medium; MSC CM alone (without MSC); MSC CM + inhibitors of PI3K (LY294002 or Wortmannin); MSC CM + antibodies neutralizing IGF 1 or VEGF; MSC + inhibitors of PI3K; or cyclosporine. Cell injury was assessed by LDH activity and MTT staining at the end of reperfusion. VEGF, IGF-1 and HGF were measured in each experimental treatment preparation. Ex vivo experimentation on isolated rat hearts subjected to I/R were performed to evaluate the protective effects of MSC CM on myocardial reperfusion injuries measured through CK release and infarct size after TTC staining. RESULTS: In vitro cell injury was significantly reduced by MSC, MSC CM and CsA. PI3K inhibitors significantly attenuated the protection afforded by MSC CM but not growth factor inhibitors. Ex vivo experimentation showed that MSC CM significantly reduced myocardial I/R injury. CONCLUSION: Our data suggest that MSC CM added at the onset of reperfusion can protect myocardium from I/R injury. In vitro data suggest a protection mediated by paracrine activation of the PI3K pathway. PMID- 21030273 TI - Linguistic correlates of self in deceptive oral autobiographical narratives. AB - The current study collected orally-delivered autobiographical narratives from a sample of 44 undergraduate students. Participants were asked to produce both deceptive and non-deceptive versions of their narrative to two specific autobiographical question prompts while standing in front of a video camera. Narratives were then analyzed with Coh-Metrix software on 33 indices of linguistic cohesion. Following a Bonferroni correction for the large number of linguistic variables (p<.002), results indicated that the deceptive narratives contained more explicit action verbs, less linguistic complexity, and less referential coherence (sentences being cohesive with each other). The results support a theory that, in deceptive narratives, there is greater narrative distance between the self that narrates and the self that is narrated about. This suggests that narrative selves are constituted not as autonomous selves, but are subject to processes (e.g., psychological, linguistic, social) that are likely operating on a subconscious level. PMID- 21030274 TI - Asymptomatic rotator cuff tears: patient demographics and baseline shoulder function. AB - BACKGROUND: The purpose of this study is to characterize the demographic features and physical function of subjects with asymptomatic rotator cuff tears and to compare their shoulder function with control subjects with an intact rotator cuff. MATERIALS AND METHODS: This study enrolled 196 subjects with an asymptomatic rotator cuff tear and 54 subjects with an intact rotator cuff presenting with a painful rotator cuff tear in the contralateral shoulder. Various demographic features, shoulder function (American Shoulder and Elbow Surgeons score and Simple Shoulder Test score), range of motion, and strength were compared. RESULTS: The demographic features of the study and control groups were similar. Hand dominance was associated with the presence of shoulder pain (P < .05). Subjects with an intact rotator cuff had greater but clinically insignificant American Shoulder and Elbow Surgeons (P < .05) and Simple Shoulder Test (P < .05) scores than those with an asymptomatic tear. No differences in functional scores, range of motion, or strength were seen between partial thickness tears (n = 61) and full-thickness tears (n = 135). Of the full thickness tears, 36 (27%) were classified as small, 85 (63%) as medium, and 14 (10%) as large. No differences were seen in functional scores among full thickness tears of various sizes. CONCLUSIONS: When asymptomatic, a rotator cuff tear is associated with a clinically insignificant loss of shoulder function compared with an intact rotator cuff. Therefore a clinically detectable decline in shoulder function may indicate an "at-risk" asymptomatic tear. The presence of pain is important in cuff-deficient shoulders for creating a measurable loss of shoulder function. Hand dominance appears to be an important risk factor for pain. PMID- 21030275 TI - Another milestone. PMID- 21030276 TI - A unilateral magnet with an extended constant magnetic field gradient. AB - Unilateral magnetic resonance (UMR) has become, in different research areas, a powerful tool to interrogate samples of arbitrary size. Numerous designs have been suggested in the literature to produce the desired magnetic field distributions, including designs which feature constant magnetic field gradients suitable for diffusion and profiling experiments. This work presents a new approach which features extended constant magnetic field gradients with a three magnet array. Constant gradients of more than 3cm extent can be achieved in a very simple, compact and safe design. Diffusion measurements from different positions over the magnet are presented in addition to practical applications for reservoir core plug characterization. The idea of a solenoid as a probe for specific measurements in UMR is introduced. Simple profiling experiments are also presented. PMID- 21030277 TI - Serum vitamin B12 concentrations within reference values do not exclude functional vitamin B12 deficiency in PKU patients of various ages. AB - Homocysteine (Hcy) and in particular methylmalonic acid (MMA) are considered reliable parameters for vitamin B(12) status in healthy individuals. Phenylketonuria (PKU) patients are at risk for functional vitamin B(12) deficiency based on their diet. OBJECTIVE: The aim of this study was to investigate the prevalence of functional vitamin B(12) deficiency in continuously treated PKU patients and the association of parameters of vitamin B(12) and metabolic control. METHODS: In 75 continuously treated PKU patients of 1-37 years of age, serum vitamin B(12) concentrations, plasma Hcy, MMA, and phenylalanine concentrations were studied. RESULTS: Eight patients had vitamin B(12) concentrations below normal. Out of these eight patients, two had elevated MMA and/or Hcy concentrations. Ten other patients with normal vitamin B(12) concentrations had elevated concentrations of MMA and/or Hcy. CONCLUSIONS: A vitamin B(12) concentration within the reference range does not automatically imply a sufficient vitamin B(12) status. We recommend measuring serum MMA, or alternatively plasma Hcy, yearly in all PKU patients to diagnose functional vitamin B(12) deficiency. PMID- 21030278 TI - Aortic involvement in giant cell arteritis: current data. AB - Aortitis due to giant cell arteritis (GCA) is rare but probably underestimated given the frequent paucity of symptoms. Thus, early studies relied on the occurrence of complications to estimate the prevalence of GCA aortitis. With this method, aortitis was a feature in 3 to 18% of GCA patients. Since then, the introduction of modern imaging techniques has established that aortitis is more common than previously thought. Aortitis should be considered in patients with atypical clinical presentations of GCA consisting, for instance, in isolated laboratory evidence of systemic inflammation or a relapse during treatment. Aortitis may be difficult to diagnose, as temporal artery biopsy has limited sensitivity in patients with predominant large-vessel involvement. Positron emission tomography (PET) and magnetic resonance imaging (MRI) are both highly effective for the early diagnosis of aortitis. Case-series evaluating PET in patients with GCA found evidence of aortitis in over half the cases, with predominant involvement of the thoracic aorta. To date, no evidence is available about the potential usefulness of PET or MRI in monitoring patients with GCA aortitis over time. Involvement of the aorta and other large arteries does not change the treatment strategy, which rests on corticosteroid therapy. Administration of a corticosteroid-sparing drug should be considered, most notably when a relapse occurs. Aortitis is associated with an increased risk of aneurysm of the thoracic aorta. Consequently, all GCA patients should be monitored for aneurysm at regular intervals, even after treatment discontinuation. The recommended strategy is an annual evaluation including a chest radiograph, echocardiogram, and abdominal Doppler sonogram; these imaging studies can be replaced by contrast-enhanced computed tomography of the chest and abdomen. PMID- 21030279 TI - [How to get an institutional review board (IRB) approval for clinical research]. PMID- 21030280 TI - [Postoperative pain after transvaginal repair of pelvic organ prolapse with or without mesh]. AB - OBJECTIVE: To assess postoperative pain after POP surgery by vaginal approach with and without mesh. PATIENTS AND METHODS: One hundred and thirty-two consecutives patients operated on for POP (POP-Q >= 2) were enrolled. Surgical procedure was a traditional repair without mesh in 66 women and a mesh repair (Prolift) in 66 women. Postoperative pain was prospectively assessed by autoadministred questionnaires including analog visual scale. Pain scores were recorded 1 day after surgery (D1), at discharge, at 1 month follow-up (M1) and at 3 to 6 months follow-up (M3-6). We focused specially on mesh repair, age, previous prolapse procedure, hysterectomy, sacrospinofixation, transobturator sling, pre- and postoperative POP-Q score. RESULTS: At discharge, pain score was significantly higher in the mesh group (1.2 +/- 1.8 versus 0.5 +/- 0.9, P=0.021). Pain score were low (VAS<3) and similar in the two groups with or without mesh at M1 and M3-6 follow-up. When focusing on associated factors, hysterectomy as a significant higher pain score at day 1, transobturator slings associated to traditional repair are more painful at D1 versus associated to mesh repair, sacrospinofixation has only a statistical tendency (P=0.08) more painful at D1. DISCUSSION AND CONCLUSION: Pain score are low after both traditional or mesh repair by vaginal route. Mesh repair, hysterectomy and sacrospinofixation are more painful only in the first days after surgery. Our study supports the theory that transvaginal mesh procedure allows a quick return to normal life. PMID- 21030281 TI - [The new insights of ovarian carcinogenesis... and their possible impacts on our current practice]. PMID- 21030282 TI - [Feasibility and results of mid-urethral sling surgery after transurethral injections for stress urinary incontinence in women]. AB - OBJECTIVE: To assess feasibility and results of mid-urethral sling placement for stress urinary incontinence (SUI) in adult women after transurethral injection therapy failure. PATIENTS AND METHODS: Eleven patients were operated on for a mid urethral sling placement after at least one transurethral injection therapy, from January 2005 to February 2008. Injections were performed for moderate non-daily SUI, or according to patient willingness, or for SUI surgical history. Mean age at the time of surgery was 59.9 years (range: 33 to 84). RESULTS: Mean operative time, including control cystoscopy time during TVT placement, was 26 minutes (20 35). There were no peri-operative complications, nor problems for dissection or tape placement. At a mean follow-up of 9.9 months (5-20), 9/11 (81%) patients were dry with no lower urinary tract disorders. DISCUSSION AND CONCLUSION: SUI treatment by mid-urethral sling after transurethral injections failure is feasible not bothered by the injected material and effective at short-term. PMID- 21030283 TI - [Salpingectomy--how I do it]. PMID- 21030284 TI - [Unknown gonadotoxicity chemotherapy and preservation of fertility: example of Temozolomide]. AB - OBJECTIVES: To evaluate the effect of Temozolomide on female fertility and the relevance of our coverage in preservation of fertility. PATIENTS AND METHODS: From 2005 to 2009, 24 patients treated with Temozolomide for a low-grade glioma were included in the study (12 women who underwent a fertility preservation consultation and 12 women who did not). A retrospective study of their medical records and sending a questionnaire were undertaken to assess their fertility after treatment. RESULTS: Of the 24 patients, 15 patients had no fertility preservation and the remaining nine had a cryopreservation of embryos with or without an oocyte cryopreservation. Four patients are or have been pregnant (delivery, spontaneous miscarriage, pregnancy being in the group of preserving fertility and a current pregnancy in the group where no fertility preservation has been achieved). DISCUSSION: First study on the effect of Temozolomide on female fertility. CONCLUSION: Temozolomide is not totally gonadotoxic. PMID- 21030285 TI - Pros and cons of post-mortem CT imaging on aspiration diagnosis. AB - Recently, the field of forensics has experienced a rapid increase in the use of modern cross-sectional imaging in forensic investigations. We examined the value of post-mortem computed tomography (CT) imaging relative to autopsy for distinguishing aspiration into the lungs from airways, from lung alterations due to other causes, and for identifying the aspirated material. We selected 54 bodies submitted to whole-body CT scanning prior to autopsy. All cases had autopsy findings of blood (31 cases), fresh water (12 cases), or gastric content (11 cases) aspiration. The radiological images were retrospectively analyzed for airway and lung aspiration. In all cases, CT imaging detected pulmonary abnormalities suggestive of aspiration. Nevertheless, analysis of the CT images alone was not able to identify the aspirated material or to distinguish pulmonary findings of aspiration from lung changes due to other causes, except for a few cases of hemo-aspiration. However, due to its ability to visualize the entire parenchyma, CT imaging was superior to autopsy in providing additional data about the distribution and severity of the aspiration as well as in detecting small abnormalities. Post-mortem CT imaging should be considered as a superior tool for forensic investigations of aspiration due to its ability to document diagnostic conclusions and to guide the forensic pathologist during lung tissue examination. PMID- 21030286 TI - Identification of dual false indirect exclusions on the D5S818 and FGA loci. AB - Here, we present a case in which the result of a maternity test was obscured due to two false indirect exclusions that occurred in two out of 15 genetic loci through the use of the AmpFlSTR Identifiler PCR Amplification kit (Applied Biosystems, Foster City, CA). The Identifiler kit failed to amplify allele 11 of the D5S818 system on the child and failed to capture the existence of allele 13 on the FGA system on both mother and child. The situation was remedied through use of the PowerPlex 16 PCR Amplification Kit (Promega, Madison, WI) which used different primers with a different allele range than that of the Identifiler kit. Maternity was confirmed through sequencing and it was found that the failure of the Identifiler kit to amplify allele 11 on the D5S818 system was the result of an incompatibility to the primer-binding site due to a mutation that changed a guanine (G) into a thymine (T) 55 base pairs (bp) downstream of the repeat. The inability of the Identifiler kit to pick up allele 13 of the FGA system was due to the out-of-range location of the allele. Indirect exclusions can be misleading if they are not fully investigated since allele range as well as primer-binding affinity are two confounders that must be addressed to ensure accuracy of the test results. PMID- 21030288 TI - Effects of CT image segmentation methods on the accuracy of long bone 3D reconstructions. AB - An accurate and accessible image segmentation method is in high demand for generating 3D bone models from CT scan data, as such models are required in many areas of medical research. Even though numerous sophisticated segmentation methods have been published over the years, most of them are not readily available to the general research community. Therefore, this study aimed to quantify the accuracy of three popular image segmentation methods, two implementations of intensity thresholding and Canny edge detection, for generating 3D models of long bones. In order to reduce user dependent errors associated with visually selecting a threshold value, we present a new approach of selecting an appropriate threshold value based on the Canny filter. A mechanical contact scanner in conjunction with a microCT scanner was utilised to generate the reference models for validating the 3D bone models generated from CT data of five intact ovine hind limbs. When the overall accuracy of the bone model is considered, the three investigated segmentation methods generated comparable results with mean errors in the range of 0.18-0.24 mm. However, for the bone diaphysis, Canny edge detection and Canny filter based thresholding generated 3D models with a significantly higher accuracy compared to those generated through visually selected thresholds. This study demonstrates that 3D models with sub voxel accuracy can be generated utilising relatively simple segmentation methods that are available to the general research community. PMID- 21030287 TI - In situ parameter identification of optimal density-elastic modulus relationships in subject-specific finite element models of the proximal femur. AB - Quantitative computed tomography based finite element analysis of the femur is currently being investigated as a method for non-invasive stiffness and strength predictions of the proximal femur. The specific objective of this study was to determine better conversion relationships from QCT-derived bone density to elastic modulus, in order to achieve accurate predictions of the overall femoral stiffness in a fall-on-the-hip loading configuration. Twenty-two femurs were scanned, segmented and meshed for finite element analysis. The elastic moduli of the elements were assigned according to the average density in the element. The femurs were then tested to fracture and force-displacement data were collected to calculate femoral stiffness. Using a training set of nine femurs, finite element analyses were performed and the parameters of the density-elastic modulus relationship were iteratively adjusted to obtain optimal stiffness predictions in a least-squares sense. The results were then validated on the remaining 13 femurs. Our novel procedure resulted in parameter identification of both power and sigmoid functions for density-elastic modulus conversion for this specific loading scenario. Our in situ estimated power law achieved improved predictions compared to published power laws, and the sigmoid function yielded even smaller prediction errors. In the future, these results will be used to further improve the femoral strength predictions of our finite element models. PMID- 21030289 TI - Manual therapy assessment findings in patients diagnosed with Eagle's Syndrome: a case series. PMID- 21030290 TI - Gas permeable lenses are alive and well in 2010. PMID- 21030292 TI - Siloxane and silsesquioxane molecules--precursors for silicate materials. AB - Preparation of ceramics by sol-gel method has been known for many years, but recently it has been developed as a method for the synthesis of nanostructural ceramic materials. Hydrolytic polycondensation of simple molecules [e.g. most widely used tetraethoxysilane (TEOS)] leads to xerogel materials that can contain macromolecules of distinct random, ladder and cage or partial cage structure. In order to obtain well-defined silsesquioxanes it is preferred to start the process with more complex molecules, bringing in a specific framework that can govern the structure of the product. In the presented work alkoxy derivatives of cyclosiloxanes and polysiloxanes as well as a hydride derivative of octahedral silsequioxane (T(8)(H)) were applied as precursors in the process of hydrolytic polycondensation. Depending on the reaction conditions, silsesquioxane macromolecules or silica material of ordered structure were obtained. We have prepared mesoporous organiosilica materials without using any template or surfactant whatsoever. The meso-pores are created due to the unique structure of initial oligosiloxane or silsequioxane molecules and the specific interactions in the used catalyst/solvent system. In the case of octasilsesquioxane precursor, the condensation process gives directly mesoporous silica material. Dried polysilsesquioxanes were heated at the temperature of 600 degrees C in argon or air atmosphere (pyrolysis or ceramization). In the atmosphere of argon SiC(x)O(y) glass materials were obtained. PMID- 21030291 TI - Chemoenzymatic methods for site-specific protein modification. AB - In the past decade, numerous chemical technologies have been developed to allow the site-specific post-translational modification of proteins. Traditionally covalent chemical protein modification has been accomplished by the attachment of synthetic groups to nucleophilic amino acids on protein surfaces. These chemistries, however, are rarely sufficiently selective to distinguish one residue within a literal sea of chemical functionality. One solution to this problem is to introduce a unique chemical handle into the target protein that is orthogonal to the remainder of the proteome. In practice, this handle can be a novel peptide sequence, which forms a 'tag' that is selectively and irreversibly modified by enzymes. Furthermore, if the enzymes can tolerate substrate analogs, it becomes possible to engineer chemically modified proteins in a site-specific fashion. This review details the significant progress in creating techniques for the chemoenzymatic generation of protein-small molecule constructs and provides examples of novel applications of these methodologies. PMID- 21030293 TI - A study of the spin-Hamiltonian parameters for the trigonal Sm3+ center in La2Mg3(NO3)(12).24H2O crystal. AB - This paper reports a theoretical calculation of spin-Hamiltonian parameters (g factors g//, g? and hyperfine structure constants 147A//, 147A?, 149A//, 149A?) for 147Sm3+ and 149Sm3+ isotopes in the trigonal La3+ site of La2Mg3(NO3)(12).24H2O crystal from a diagonalization (of energy matrix) method. In the method, the Hamiltonian concerning the energy matrix includes the Zeeman and hyperfine interaction terms and so there is no perturbation calculation in it. The crystal-field parameters in the energy matrix are calculated using the superposition model, in which the structural data of 12-fold coordinated site rather than those of the incorrect 6-fold coordinated site given in the previous paper are applied. The calculated results are in reasonable agreement with the experimental results. The results are discussed. PMID- 21030294 TI - Study and fabrication of europium picrate triethylene glycol complex. AB - A mononuclear of [Eu(NO3)(Pic)(H2O)2(EO3)](Pic).(0.73)H2O complex, where EO3=trietraethylene glycol and Pic=picrate anion, shows a red emission when used as an active layer in a single layer of ITO/EO3-Eu-Pic/Al configuration. The crystal structure of the complex consists of [Eu(NO3)(Pic)(H2O)2(EO3)]+ cation and [Pic]- anion. The Eu(III) ion is coordinated to the 10 oxygen atoms from one EO3 ligand, one Pic anion, one nitrate anion, and two water molecules. The complex is crystallized in triclinic with space group P-1. The hybrids in thin films I and II were prepared in the respective order solution concentrations of 15 and 20 mg/mL the emissive center. Comparing the photoluminescence (PL) and electroluminescence (EL) spectra, we can find that all emissions come from the characteristic transitions of the Eu(III) ion. The EL spectra of both thin films showed the occurrence of the most intense red-light emission around at 612 nm. Comparison of organic light-emitting device (OLED) current intensity characteristics as a function of voltage (I-V) show that the thin film I is better than those found for the thin film II. The thickness of the emitting layer is an important factor to control the current-voltage curve. The sharp and intense emission of the complex at low voltage indicates that the complex is a suitable and promising candidate for red-emitting materials. PMID- 21030295 TI - Mangifera indica leaf-assisted biosynthesis of well-dispersed silver nanoparticles. AB - The use of various parts of plants for the synthesis of nanoparticles is considered as a green technology as it does not involve any harmful chemicals. The present study reports a facile and rapid biosynthesis of well-dispersed silver nanoparticles. The method developed is environmentally friendly and allows the reduction to be accelerated by changing the temperature and pH of the reaction mixture consisting of aqueous AgNO3 and Mangifera Indica leaf extract. At a pH of 8, the colloid consists of well-dispersed triangular, hexagonal and nearly spherical nanoparticles having size ~20 nm. The UV-vis spectrum of silver nanoparticles gave surface plasmon resonance (SPR) at 439 nm. The synthesized nanocrystals were characterized using transmission electron microscopy (TEM), X ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy. Water soluble organics present in the leaf are responsible for the reduction of silver ions. This green method provides faster synthesis comparable to chemical methods and can be used in areas such as cosmetics, foods and medical applications. PMID- 21030296 TI - Investigations of zero-field splitting (ZFS) and local distortion parameters of ZnAl2S4:Mn2+ by theoretical analysis. AB - Fourth-order perturbation formula on the basis of the dominant spin-orbit coupling mechanism is employed to investigate the local environment around Mn2+ centers in ZnAl2S4 single crystals. The zero-field splitting (ZFS) parameter D is calculated for the Mn2+ ions at the Al3+ site with local symmetry D3d using the different orbital reduction factors. Both the contributions of the lattice distortions to the crystal-field (CF) parameters and the D are examined by means of different cases. The comparison between the calculated results in this study and the previous experimental and theoretical values reveals a good agreement and reasonable distortion parameters for Mn2+ ions at Al3+ sites. PMID- 21030297 TI - Solvent effect on the optical property of uranyl acetylacetonate monohydrate. AB - The lability of the [UO2(acac)2H2O] complex has been exploited to decipher solvent composition of a medium. Successive blue shift of the pi-pi* band (lambdamax=282 nm) is observed due to alcohol substitution of increasing chain length in place of water. This observation helps to quantify the chain lengths of normal alcohol. The result has been accounted theoretically. However, in non coordinating solvent, irregular red shift of the pi-pi* band is observed because of the molecular complexity. Again, charge transfer (CT) band at 211 nm has been identified employing polar-polar and polar coordinating-non-coordinating solvent systems. PMID- 21030298 TI - Conformational stability, r0 structural parameters, and vibrational assignments of mono-substituted cyclobutanes: fluorocyclobutane. AB - Variable temperature (-55 to -100 degrees C) studies of the infrared spectra (3500-400 cm(-1)) of fluorocyclobutane, c-C(4)H(7)F, dissolved in liquid xenon have been carried out as well as the infrared spectra of the gas. By utilizing eight pairs of conformers at 10 different temperatures, the enthalpy difference between the more stable equatorial conformer and the axial form has been determined to be 496+/-40 cm(-1) (5.93+/-0.48 kJ/mol). The percentage of the axial conformer present at ambient temperature is estimated to be 8+/-1%. The ab initio MP2(full) average predicted energy difference from a variety of basis sets is 732+/-47 cm(-1) (9.04+/-0.44 kJ/mol) and the average value of 602+/-20 cm(-1) from density functional theory predictions by the B3LYP method are significantly larger than the experimentally determined enthalpy value. By utilizing previously reported microwave rotational constants for the equatorial and axial conformers combined with ab initio MP2(full)/6-311+G(d,p) predicted structural values, adjusted r(0) parameters have been obtained. The determined heavy atom structural parameters for the equatorial [axial] conformer are: distances (A) C-F=1.383(3) [1.407(3)], C(alpha)-C(beta)=1.543(3) [1.546(3)], C(beta)-C(gamma)=1.554(3) [1.554(3)] and angles ( degrees ) ?C(alpha)C(beta)C(gamma)=85.0(5) [89.2(5)], ?C(beta)C(alpha)C(beta)=89.3(5) [89.2(5)], ?F-(C(beta)C(alpha)C(beta))=117.4(5) [109.2(5)] and a puckering angle of 37.4(5) [20.7(5)]. The conformational stabilities, harmonic force fields, infrared intensities, Raman activities, depolarization ratios and vibrational frequencies have been obtained for both conformers from MP2(full)/6-31G(d) ab initio calculations and compared to experimental values where available. The results are discussed and compared to the corresponding properties of some other monosubstituted cyclobutanes with halogen and pseudo-halogen substituents. PMID- 21030299 TI - Vibrational spectra and DFT study of anticancer active molecule 2-(4-Bromophenyl) 1H-benzimidazole by normal coordinate analysis. AB - FT-IR and FT-Raman spectra of the 2-(4-Bromophenyl)-1H-benzimidzole were recorded and analyzed in the solid phase. The optimized molecular geometry, the vibrational wavenumbers, the infrared intensities and the Raman scattering activities were calculated by using Hartree-Fock and density functional method (B3LYP) with 6-31G(d,p) basis set. The potential surface scan study was carried out for the conformation of theoretical structure. Detailed interpretation of the vibrational spectra had been carried out with the aid of the normal coordinate analysis. Chemical interpretation of hyperconjugative interaction was done by natural bond orbital analysis. PMID- 21030300 TI - Electrogenerated chemiluminesence method for the determination of riboflavin at an ionic liquid modified gold electrode. AB - A highly sensitive electrogenerated chemiluminescence (ECL) method for the determination of riboflavin was developed based on the enhancement of ECL intensity of lucigenin at room temperature ionic liquids (RTILs) modified gold electrode. RTILs modified gold electrode exhibited excellent electrochemical and ECL property to lucigenin system and the ECL intensity of lucigenin was greatly enhanced by riboflavin. The characterization of the RTILs modified electrode and the attractive performance of the sensitive ECL method for the determination of riboflavin were investigated. Under the optimized conditions, the ECL intensity was directly proportional to the concentration of riboflavin in the range from 5.0*10(-10) g/mL to 1.0*10(-8)g/mL with the detection limit of 1*10(-10) g/mL. The method has been applied to the determination of riboflavin in the pharmaceutical preparations with satisfactory recovery from 96% to 101%. This work demonstrates that the incorporation of ECL method with RTILs modified electrode is a promising strategy for the determination of organic compounds with high sensitivity and good reproducibility. PMID- 21030301 TI - Joint angle variability in the time course of reaching movements. AB - OBJECTIVE: Investigating motor control processes is of primary interest in a number of scientific and practical fields. Movement variability is of increasing interest in this context. However, until now little has been known about the time course of variability during movement execution. The objective of this study was to investigate the influence of visual information and task specification on the variability of joint angle motion in reaching movements. METHODS: Subjects repetitively reached for a handle. Movement variability was quantified by the within-subjects standard deviation of mean joint angle. The analysis focused on the time course of variability during movement execution. RESULTS: The availability of visual information did not influence the time course of joint angle variability whereas task specification on reaching accuracy did. Under high accuracy demand variability was reduced more strongly after reaching its maximum. CONCLUSIONS: Results suggest that the availability of visual information plays a minor role in the control of well-trained reaching movements. This suggests that proprioceptive information is the main feedback source to control these movements. SIGNIFICANCE: The analysis of the time course of movement variability might be a valuable method to investigate the central or peripheral causes of movement disorders for diagnostic and rehabilitation purposes. PMID- 21030303 TI - Low level occupational exposure to styrene: its effects on DNA damage and DNA repair. AB - The present study aimed to evaluate the effects of styrene exposure at levels below the recommended standards of the Threshold Limit Value (TLV-TWA(8)) of 20 ppm (ACGIH, 2004) in reinforced-fiberglass plastics workers. Study subjects comprised 50 exposed workers and 40 control subjects. The exposed workers were stratified by styrene exposure levels, i.e. group I (<10 ppm, <42.20 mg/m(3)), group II (10-20 ppm, 42.20-84.40 mg/m(3)), and group III (>20 ppm, >84.40 mg/m(3)). The mean styrene exposure levels of exposed workers were significantly higher than those of the control workers. Biomarkers of exposure to styrene, including blood styrene and the urinary metabolites, mandelic acid (MA) and phenylglyoxylic acid (PGA), were significantly increased with increasing levels of styrene exposure, but were not detected in the control group. DNA damage, such as DNA strand breaks, 8-hydroxydeoxyguanosine (8-OHdG), and DNA repair capacity, were used as biomarkers of early biological effects. DNA strand breaks and 8 OHdG/10(5)dG levels in peripheral leukocytes of exposed groups were significantly higher compared to the control group (P<0.05). In addition, DNA repair capacity, determined by the cytogenetic challenge assay, was lower in all exposed groups when compared to the control group (P<0.05). The expression of CYP2E1, which is involved in styrene metabolism, in all styrene exposed groups, was higher than that of the control group at a statistically significant level (P<0.05). Levels of expression of the DNA repair genes hOGG1 and XRCC1 were significantly higher in all exposed groups than in the control group (P<0.05). In addition to styrene contamination in ambient air, a trace amount of benzene was also found but, the correlation between benzene exposure and DNA damage or DNA repair capacity was not statistically significant. The results obtained from this study indicate an increase in genotoxic effects and thus health risk from occupational styrene exposure, even at levels below the recommended TLV-TWA(8) of 20 ppm. PMID- 21030302 TI - Ictal and interictal high frequency oscillations in patients with focal epilepsy. AB - OBJECTIVE: High frequency oscillations (HFOs) can be recorded with depth electrodes in focal epilepsy patients. They occur during seizures and interictally and seem important in seizure genesis. We investigated whether interictal and ictal HFOs occur in the same regions and how they relate to epileptiform spikes. METHODS: In 25 patients, spikes, ripples (80-250 Hz) and fast ripples (FR: 250-500 Hz) and their co-occurrences were marked during interictal slow wave sleep (5-10 min), during 10 pre-ictal seconds and 5s following seizure onset. We compared occurrence and spatial distribution between these periods. RESULTS: HFOs and spikes increased from interictal to ictal periods: the percentage of time occupied by ripples increased from 2.3% to 6.5%, FR from 0.2% to 0.8%, spikes from 1.1% to 4.8%. HFOs increased from interictal to pre-ictal periods in contrast to spikes. Spikes were in different channels in the interictal, pre-ictal and ictal periods whereas HFOs largely remained in the same channels. CONCLUSIONS: HFOs remain confined to the same, possibly epileptogenic, area, during interictal and ictal periods, while spikes are more widespread during seizures than interictally. SIGNIFICANCE: Ictal and interictal HFOs represent the same (epileptogenic) area and are probably similar phenomena. PMID- 21030304 TI - The role of pre-pregnancy physical activity and sedentary behaviour in the development of gestational diabetes mellitus. AB - Gestational diabetes mellitus (GDM) complicates approximately 3-11% of pregnancies and increases the risk on prenatal morbidity and later development of type 2 diabetes mellitus. Physical activity and sedentary behaviour are thought to play a role in the development of GDM, independent of overweight and obesity. The aim of this study was to examine the relationships between physical activity, sedentary behaviour and the development of GDM using a population-based prospective cohort study. Data from the youngest (1973-1978) cohort of the Australian Longitudinal Study on Women's Health (n=2913) were used to determine the influences of self-reported physical activity, and sedentary behaviour in 2000 and 2003 on the development of GDM over subsequent three year periods, with adjustment for socio-demographic and lifestyle factors. In this cohort of Australian women, physical activity and sedentary behaviour in 2000 and 2003 were not associated with the development of GDM in the subsequent three years. In adjusted models, odds ratios for the development of GDM were 1.92 (95% CI 1.25 2.96) for overweight women (BMI 25-30 kg/m2) and 3.11 (1.92-5.03) for obese women (BMI>=30 kg/m2) compared with normal weight women. Those with lower education and women born in an Asian country also had higher risk of developing GDM than more highly educated and Australian born women, respectively. In conclusion, pre pregnancy physical activity and sedentary behaviour appear to be less important in the development of GDM in this cohort than overweight and obesity. PMID- 21030306 TI - Langerhans cells in innate defense against pathogens. AB - Langerhans cells (LCs) are at the frontline in defense against mucosal infections because they line the mucosal tissues and are ideally situated to intercept pathogens. Recent data suggest that LCs have an innate anti-HIV-1 function. LCs express the LC-specific C-type lectin Langerin that efficiently captures HIV-1, which prevents HIV-1 transmission. However, immune activation of LCs changes these protective cells into HIV-1-transmitting cells, which indicates that the antiviral function of LCs depends on several factors including co-infections. In this review, we discuss the dual role of LCs in innate defense against pathogens, with a focus on HIV-1 dissemination. PMID- 21030305 TI - Development and homeostasis of 'resident' myeloid cells: the case of the Langerhans cell. AB - Langerhans cells (LCs) are myeloid cells of the epidermis, featured in immunology textbooks as bone marrow-derived antigen-presenting dendritic cells (DCs). A new picture of LC origin, homeostasis and function has emerged, however, after genetic labelling and conditional cell ablation models in mice. LC precursors are recruited into the fetal epidermis, where they differentiate and proliferate in situ. In adults, LCs proliferate at steady state, and during inflammation, in response to signals from neighbouring cells. Here we review the experimental evidence that support either extra-embryonic yolk sac (YS) macrophages or hematopoietic stem cells (HSCs) as the origin of LCs. Beyond LC biology, we propose that YS and HSCs can contribute to the development of distinct subsets of macrophages and DCs. PMID- 21030307 TI - Pitfalls in new artemisinin-containing antimalarial drug development. AB - Artemisinin combination therapy (ACT) paves the way for new opportunities to eliminate malaria in the tropics. However, the huge increase of ACT consumption raises major concerns about their availability over the next few years. At the same time a decrease in their efficacy has already been reported. Alongside the deployment of multifocal control programs, the process ranging from artemisia crop production to accreditation of new ACT combinations urgently needs to be strengthened to supply sufficient quantities of high-quality drugs. New suppliers will have the opportunity to enter this market to develop new formulations, and bioequivalence studies are required to validate these new formulations. It is thus crucial for national malaria control teams to be able to better scrutinize the dossier of these new formulations. PMID- 21030308 TI - Identification of anti-PP1P(k) in a blood donor and her family: a case report following her pregnancy and review. AB - Anti-PP1P(k) is a rare, biphasic antibody with the ability to cause immediate hemolytic transfusion reactions and early spontaneous abortions. The antibody is formed by individuals with the p phenotype. A blood donor with anti-PP1P(k) and the p phenotype was identified through routine donor screening. A sister was found to also be p phenotype. At that time, the sister was 24weeks pregnant. Subsequently, the original blood donor became pregnant. Both individuals were followed throughout their pregnancies and delivered infants without complications from anti-PP1P(k) antibodies. The literature regarding anti-PP1P(k), the p phenotype, and recurrent pregnancy loss in this setting is reviewed. PMID- 21030309 TI - Transfusion-associated graft-versus-host-disease: case report and review of literature. AB - Transfusion-associated graft-versus-host disease (GVHD) is a rare condition that can occur after receipt of any cellular blood component with viable lymphocytes. Pathogenesis depends on immunocompetent donor T lymphocytes and a host immune system unable to clear donor cells before they proliferate, engraft, and attack host cells. Unlike bone marrow transplantation-associated GVHD, transfusion associated disease destroys marrow stem cells early in the course of the disease, resulting in pancytopenia contributing to a fulminant clinical course and nearly 100% mortality. Transfusion-associated disease may be diagnosed late or completely missed; thus, true incidence rates are uncertain. We report our experience with an oncology patient who developed transfusion-associated GVHD. This report also reviews the literature to discuss established GVHD risk factors as well as provide recommendations for standardized reporting to better understand incidence rates and possible risk factors. This information would allow individual physicians and blood bank associations to make more informed decisions on the use of irradiated blood products. PMID- 21030310 TI - Transfusion demand control strategies: potential efficacy of hospital and regional interventions. AB - INTRODUCTION: Contingency plans have been developed to direct appropriate responses to blood shortages. Planning requires an understanding of the potential savings of different conservation strategies. METHOD: The Australian Capital Territory (ACT) Haemovigilance and ACT Pathology transfusion databases were reviewed from March to September 2003. All transfusion episodes were prioritised in accordance with the Australian National Blood Supply Contingency Plan. The number of red cell transfusions related to various indications, their appropriateness and acuity was determined. The potential reduction in red cell usage was modelled for potential red cell reduction interventions. RESULTS: There were 2305 units of red cells captured during the timeframes of the audits. This accounted for an estimated 70% of all red cell transfusions in the ACT. After correcting for the number of red cells transfused at each hospital, red cells were prioritised as category 1 in 59%, 2 in 27% and 3 in 13%. The remainder had insufficient data for classification. Transfusion for elective surgery accounted for 14.7% of red cells used, with 9.0% rated category 3 under the contingency plan. There were 17.3% of red cells transfused for inappropriate indications, when reviewed against national guidelines. After excluding inappropriate transfusions, cancelling elective surgery could potentially save a further 5.5% and 4.3% of blood utilisation for category 3 and 2 patients, respectively. Significant differences were found between hospitals. CONCLUSION: Targeting inappropriate transfusions by vetting particularly for inappropriate transfusions not only re-directs blood away from those unlikely to benefit, but is also more effective at preserving the red blood cells than other measures during times of supply limitation. Contingency planning needs to accommodate the variable case mix in hospitals, allocate resources for transfusion medicine specialists to review every transfusion request and may be better coordinated at a jurisdictional level. PMID- 21030311 TI - Patients' experiences with symptoms and needs in the early rehabilitation phase after coronary artery bypass grafting. AB - BACKGROUND: The first month after discharge for Coronary artery bypass graft (CABG) is particularly challenging for the patients. A larger interview study is warranted to elicit CABG patients' detailed experiences, and give direction for future clinical practice. AIM: To explore the CABG patients' symptoms and needs in the early rehabilitation phase. METHODS: A qualitative, mixed method design integrating qualitative and quantitative approaches was used. Ninety-three CABG patients aged 39-77, participated in interviews at home after 2 and 4 weeks. The semi-structured interview guide covered: experiences of relief of angina pectoris after surgery, experiences with prescribed discharge medications, psychological experiences: anxiety, depression, sexuality, health professional contact persons, and patient defined experiences. RESULTS: Two weeks after CABG the patients symptoms and needs were characterised by a substantial amount of uncertainty and worries related to what to expect and what was normal for postoperative pain, assessment and sensation of surgical site, different experiences with physical activity/exercise, uncertainty about medications, difficulties with sleep pattern, irritability, postoperative complications,uncertainty about return to work, and insufficient information at discharge. Four weeks after surgery the patients' symptom level was decreased, and they experienced life beginning to return back to normal. Patency with grafts after CABG, decision to drive a car, impotence (erectile dysfunction), and a missing link to the hospital remained challenges. CONCLUSION: CABG patients' experiences indicate a need to extend the hospital's discharge care to the first month after surgery for specific themes to promote rehabilitation outcomes. PMID- 21030312 TI - Functional characterization of plant small RNAs based on next-generation sequencing data. AB - The currently developed next-generation sequencing (NGS) technology has significantly enhanced our capacity of small RNA (sRNA) exploration. Several ambitious sRNA projects have been established based on the technical support of NGS. Thanks to the high-throughput feature of NGS, huge amounts of sRNA sequencing data have been generated. However, much more research efforts are needed to further exploit these valuable data. In this study, we carried out functional analyses of sRNAs from 26 angiosperms by utilizing public sRNA NGS data. We proposed that the endogenous sRNAs largely represented by the 24-nt ones had a potential role in transposable element (TE) control in both Arabidopsis (Arabidopsis thaliana) and rice (Oryza sativa), based on the comparison of sRNA locus densities within the TEs to the non-TE genes. Functional analysis was performed for the predicted targets of the conserved sRNAs that were classified into eudicot-specific, monocot-specific, and angiosperm-conserved ones. Moreover, several miRNA families were found to be highly conserved, and miR396 was suggested to be the most conserved miRNA family between the eudicots and the monocots, indicating its essential role in angiosperm development. At last, we demonstrated that it was a great challenge for researchers to fully exploit these huge sRNA NGS datasets and numerous sRNA species remained to be uncovered and functionally characterized. PMID- 21030313 TI - In silico identification of conserved microRNAs and their target transcripts from expressed sequence tags of three earthworm species. AB - MicroRNAs are a recently identified class of small regulatory RNAs that target more than 30% protein-coding genes. Elevating evidence shows that miRNAs play a critical role in many biological processes, including developmental timing, tissue differentiation, and response to chemical exposure. In this study, we applied a computational approach to analyze expressed sequence tags, and identified 32 miRNAs belonging to 22 miRNA families, in three earthworm species Eisenia fetida, Eisenia andrei, and Lumbricus rubellus. These newly identified earthworm miRNAs possess a difference of 2-4 nucleotides from their homologous counterparts in Caenorhabditis elegans. They also share similar features with other known animal miRNAs, for instance, the nucleotide U being dominant in both mature and pre-miRNA sequences, particularly in the first position of mature miRNA sequences at the 5' end. The newly identified earthworm miRNAs putatively regulate mRNA genes that are involved in many important biological processes and pathways related to development, growth, locomotion, and reproduction as well as response to stresses, particularly oxidative stress. Future efforts will focus on experimental validation of their presence and target mRNA genes to further elucidate their biological functions in earthworms. PMID- 21030314 TI - Clostridium difficile-associated disease among patients in Dhahran, Saudi Arabia. AB - Clostridium difficile-associated diarrhea (CDAD) is an important healthcare associated infection. However, there are no data from Saudi Arabia on this disease. A two-year prospective, observational study on the incidence of CDAD in a hospital in Saudi Arabia was carried out. Stool analysis for C. difficile toxins A and B was carried out by an enzyme-linked immunosorbent assay. Medical and laboratory records were reviewed. Of the total number of patients, there were 53.3% male and the mean age was 44.6 +/- 27.2 years. Of the 913 specimens, only 42 (4.6%) were positive for C. difficile toxins. The annual incidence rates of C. difficile were 1.2 and 0.9 per 1000 discharges, and 2.4 and 1.7 per 10,000 patient days in 2007 and 2008, respectively. Of the total number of cases, 52.4% were with onset in the hospital, 38.1% were with onset in the community and 9.5% were community-onset but healthcare facility-associated CDAD. Of the cases, 16 (39%) patients did not have exposure to antimicrobial drugs in the 3 months prior to the test date. The remaining patients received antimicrobial drug therapy. Cephalosporin and fluoroquinolone were the most common antimicrobial drugs used. Overall, the prevalence of C. difficile-associated diarrhea was low; further studies are required in Saudi Arabia to elucidate the true prevalence of the disease. PMID- 21030315 TI - Feasibility of automated warning in subjects with localization-related epilepsies. AB - Automated seizure detection ushers the prospect for issuance of warning, but to benefit from it, patients must be responsive when warnings are issued. By use of a complex reaction time test triggered by a seizure detection algorithm, the latency to impairment of responsiveness was measured during seizure versus interictal conditions in 14 patients undergoing surgical evaluation with intracranial electrodes. Mean latency to impairment of responsiveness from electrographic onset was 27.1, 42.8, or 56.1 seconds depending on the stringency of the defining criterion. Mean, SD, and distributions of compliance and percentage of correct responses did not significantly differ between seizure and interictal tests. If reproduced in studies performed under more realistic conditions, the latency to impairment of responsiveness justifies the development of a warning device to allow patients to perform activities precluded by seizures and decrease the risk of injury. If endowed with automated therapy delivery, said device would advance epilepsy management cost-effectively. PMID- 21030316 TI - Functional MRI interactions between dysplastic nodules and overlying cortex in periventricular nodular heterotopia. AB - Periventricular nodular heterotopia (PVNH) is a malformation of cortical development associated with epilepsy. It is unclear whether the epileptogenic focus is the nodule, overlying cortex, or both. We performed electroencephalography (EEG)-functional magnetic resonance imaging (fMRI) in a patient with bilateral PVNH, capturing 45 "left temporal" epileptiform discharges. The relative time at which fMRI-involved regions became active was assessed. Additionally, nodule-cortex interactions were explored using fMRI functional connectivity. There was EEG-fMRI activity in specific periventricular nodules and overlying cortex in the left temporoparietal region. In both nodules and cortex, the peak BOLD response to epileptiform events occurred earlier than expected from standard fMRI hemodynamic modeling. Functional connectivity showed nodule-cortex interactions to be strong in this region, even when the influence of fMRI activity fluctuations due to spiking was removed. Nonepileptogenic, contralateral nodules did not show connectivity with overlying cortex. EEG-fMRI and functional connectivity can help identify which of the multiple abnormal regions are epileptogenic in PVNH. PMID- 21030317 TI - Comparison of IPSA with dose-point optimization and manual optimization for interstitial template brachytherapy for gynecologic cancers. AB - PURPOSE: To compare inverse planning simulated annealing (IPSA) algorithm with the dose-point optimized (DPO) plan and manual/graphically optimized (GrO) plan for interstitial template brachytherapy for gynecologic cancers. METHODS AND MATERIALS: The data set of 10 consecutive patients was selected for this dosimetric study. For each patient, three plans were calculated: DPO, GrO, and IPSA. Dose-volume parameters from the three plans were compared to analyze the dosimetric outcome. RESULTS: Coverage of the clinical target volume (CTV) with GrO plan and IPSA algorithm was significantly better (mean V(100) of 88.8% and 89.1%; p=0.006) as compared with DPO plan (83.7%; p=0.62). Similarly, mean D(90) was same in both GrO plan and IPSA, 3.96+/-0.23 and 3.96+/-0.15Gy, respectively. DPO plans were homogeneous with homogeneity index being 0.82 as compared with 0.68+/-0.05 of GrO plan and 0.71+/-0.04 of IPSA. However, IPSA resulted in high conformity with conformity index of 0.78 as compared with 0.72 (p=0.001) and 0.68 (p<=0.001) for GrO and DPO plans, respectively. The dose to rectum (3.3+/-1.06Gy) and bladder (3.17+/-0.5Gy) was generally high for DPO plan. GrO plan reduced the dose to the rectum (2.91+/-0.63; p=0.011) and bladder (2.89+/-0.63Gy; p=0.003) significantly. IPSA resulted in a further reduction of the dose to rectum (2.79+/ 0.67Gy; p=0.046) and bladder (2.81+/-0.67Gy; p=0.035), however with no statistical significance as compared with GrO plan. CONCLUSION: IPSA resulted in significant sparing of normal tissues without compromising CTV coverage as compared with DPO plan. However, IPSA did not show any significant improvement either in CTV coverage or in normal tissue sparing as compared with GrO plan. IPSA was found to be superior in terms of homogeneity and conformity as compared with GrO plan. PMID- 21030318 TI - Urethral toxicity vs. cancer control--lessons to be learned from high-dose rate brachytherapy combined with intensity-modulated radiation therapy in intermediate and high-risk prostate cancer. AB - PURPOSE: To describe biochemical relapse-free survival (BRFS) and late toxicity after combined high-dose rate brachytherapy (HDR-B) and intensity-modulated radiation therapy (IMRT) in intermediate- and high-risk prostate cancer patients. METHODS AND MATERIALS: From March 2003 to September 2005, 64 men were treated by 3*7Gy HDR-B using one implant followed by 50Gy IMRT. Median age was 66.1 years; risk of recurrence was intermediate in 30 (47%) or high in 34 (53%) patients. Forty-four (69%) patients received hormonal therapy. Patients were treated with a median of 13 HDR-B applicators (range, 8-17). Biochemical relapse was defined according to Phoenix criteria. Toxicity was scored according to the Common Toxicity Criteria scale version 3.0. RESULTS: Median followup was 5.1 years. The 3-year BRFS was 100% and 91% for intermediate- and high-risk patients. Late Grade 2 gastrointestinal (GI) toxicity occurred in 3 (4.7%) patients, late Grade 3 GI toxicity was absent. Late Grade 3 and 4 genitourinary (GU) toxicity was observed in 7 (10.9%) and 2 (3.1%) patients. The 5-year Grade 3 or higher late GU toxicity free survival was associated with a higher number of HDR-B applicators (p=0.049). CONCLUSIONS: The 3-year BRFS was excellent and late GI toxicity was negligible. However, the late Grade 3 and 4 GU toxicity was unacceptably high. PMID- 21030319 TI - Combination of IG-IMRT and permanent source prostate brachytherapy in patients with organ-confined prostate cancer: GU and GI toxicity and effect on erectile function. AB - PURPOSE: To assess toxicity outcomes of image-guided intensity-modulated radiation therapy (IG-IMRT) combined with permanent prostate seed implant in a cohort of patients with localized prostate cancer. METHODS AND MATERIALS: A retrospective analysis was performed on 67 patients with the median pretreatment prostate-specific antigen level of 5.4. The Gleason score was less than 7 in 7 patients, 7 in 52 patients, and greater than 7 in 8 patients. The median followup was 28.2 months (range, 12-89.5 months). Treatment consisted of 45 (n=65) or 50.4 Gy (n=2) at 1.8 Gy/fraction of IG-IMRT to the prostate and seminal vesicles. Eight patients had simultaneous irradiation of pelvic lymph nodes to 45 (n=65) or 50.4 Gy (n=2). After IG-IMRT, patients received transperineal prostate implant boost with either (103)Pd (n=65, the prescribed D(90) of 100 Gy) or (125)I (n=2, D(90) of 110 Gy). Eleven patients received androgen deprivation therapy with radiotherapy. RESULTS: Toxicity higher than Grade 3 was not observed. The combined incidence of acute and late Grade 3 genitourinary toxicity was 6%. The combined incidence of acute and late Grade 3 gastrointestinal toxicity was 3%. At least one episode of gastrointestinal bleeding on followup, which could be attributed to radiation, was recorded in 14.9% of patients. For patients achieving erections before radiation, the 3-year Kaplan-Meier potency preservation rate was 66.5%. CONCLUSIONS: The early toxicity of the combination of IG-IMRT and low-dose rate brachytherapy boost in this study was favorable. PMID- 21030320 TI - Mutant cells defective in DNA repair pathways provide a sensitive high-throughput assay for genotoxicity. AB - Chemicals used industrially and commercially are required by law to be assessed for their genotoxic potential. However, all currently used assays have major limitations and despite intense effort, there is no universal agreement on which tests should be employed, or how to interpret results. We have developed a new assay system using the chicken DT40 B cell line that offers a number of significant advantages over current methodologies. Our assay could provide enhanced sensitivity using genetically defined and phenotypically characterized mutants defective in DNA repair pathways. Furthermore, analysis of the mutants, using DNA repair proficient wild-type cells as a negative control, minimizes false negative outcomes. Assessing the different responses of a panel of mutants representative of all repair pathways, mechanistic detail of genotoxicity can be determined. This unique feature, as well as reducing the false positive rate, strengthens positive identifications and is useful when extrapolating results to the human context. Our panel of mutants is likely to be useful in screening large compound libraries for an emerging class of chemotherapeutic drugs, which includes inhibitors of DNA repair enzymes such as PARP and DNA polymerases. PMID- 21030322 TI - Possible role of Artemis c.512C>G polymorphic variant in Omenn syndrome. PMID- 21030321 TI - A structural model for regulation of NHEJ by DNA-PKcs autophosphorylation. AB - The DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and Ku heterodimer together form the biologically critical DNA-PK complex that plays key roles in the repair of ionizing radiation-induced DNA double-strand breaks through the non homologous end-joining (NHEJ) pathway. Despite elegant and informative electron microscopy studies, the mechanism by which DNA-PK co-ordinates the initiation of NHEJ has been enigmatic due to limited structural information. Here, we discuss how the recently described small angle X-ray scattering structures of full-length Ku heterodimer and DNA-PKcs in solution, combined with a breakthrough DNA-PKcs crystal structure, provide significant insights into the early stages of NHEJ. Dynamic structural changes associated with a functionally important cluster of autophosphorylation sites play a significant role in regulating the dissociation of DNA-PKcs from Ku and DNA. These new structural insights have implications for understanding the formation and control of the DNA-PK synaptic complex, DNA-PKcs activation and initiation of NHEJ. More generally, they provide prototypic information for the phosphatidylinositol-3 kinase-like (PIKK) family of serine/threonine protein kinases that includes Ataxia Telangiectasia-Mutated (ATM) and ATM-, Rad3-related (ATR) as well as DNA-PKcs. PMID- 21030323 TI - Direct quantification of dimethylsulfoniopropionate (DMSP) with hydrophilic interaction liquid chromatography/mass spectrometry. AB - A simple, derivatization free method for the direct determination of dimethylsulfoniopropionate (DMSP) using hydrophilic interaction liquid chromatography (HILIC)/mass spectrometry is introduced. DMSP is a zwitterionic osmolyte which is produced from marine plankton, macro algae and higher plants. Due to its central role in climate relevant geochemical processes as well as in plant physiology and chemical ecology there is a great interest in methods for its quantification. Since DMSP is labile and difficult to extract currently most protocols for quantification are based on indirect methods. Here we show that ultra performance liquid chromatography/mass spectrometry using a HILIC stationary phase is suitable for the direct quantification of DMSP from aqueous samples and microalgal extracts. The protocol requires minimal sample preparation and phytoplankton samples can be investigated after filtration of small volumes. The limit of detection is 20nM and the calibration curve is linear in the range of 60nM to 50MUM. The use of [(2)H(6)]-DMSP as internal standard allows prolonged sample storage since it is transformed with the same kinetics as natural DMSP. This makes the method suitable for both laboratory and field studies. PMID- 21030324 TI - A fast and simple assay for busulfan in serum or plasma by liquid chromatography tandem mass spectrometry using turbulent flow online extraction technology. AB - Busulfan is used in myeloablative preparation regimens for hematopoietic bone marrow transplantation. Due to its narrow therapeutic range therapeutic drug monitoring of busulfan is recommended. In this study a fast and simple method for measuring busulfan in serum or plasma by liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been developed utilizing turbulent flow online extraction technology. Serum or plasma was mixed with acetonitrile containing d(8)-busulfan. After centrifugation the supernatant was injected onto a turbulent flow preparatory column then transferred to a C18 analytical column monitored by a tandem mass spectrometer set at positive electrospray ionization. The analytical cycle time was 4.0min. The method was linear from 0.15 to 41.90MUmol/L with an accuracy of 87.9-103.0%. Inter- and intra-assay CVs across four concentration levels were 2.1-7.8%. No significant carryover or ion suppression was observed. No interference was observed from commercial control materials containing more than 100 compounds. Comparison with a well established LC-MS/MS method using patient specimens (n=45) showed a mean bias 1.3% with Deming regression of slope 1.02, intercept -0.02MUmol/L, and a linear correlation coefficient 0.9883. The LC-MS/MS method coupled with turbulent flow online sample cleaning technology described here offers reliable busulfan quantitation in serum or plasma with minimum manual sample preparation and was fully validated for clinical use. PMID- 21030325 TI - Natural patterns of energy dispersal. AB - Universal patterns such as power-law dependences, skewed distributions, tree-like structures, networks and spirals are associated with energy dispersal processes using the principle of least action. Also ubiquitous temporal courses such as sigmoid growth, bifurcations and chaos are ascribed to the decrease of free energy in the least time. Moreover, emergence of natural standards such as the common genetic code and chirality consensus of amino acids are understood to follow from the quest to maximize the dispersal of energy. Many mathematical functions that model natural patterns and processes are found as approximations of the evolutionary equation of motion that has been derived from statistical physics of open systems. The evolutionary processes can be described as flows of energy that run from high energy sources to low energy sinks in the least time. However, the equation of evolution cannot be solved in general because the flows of energy and their driving forces are inseparable. Since the energy of the system keeps changing, the paths of evolution cannot be integrated from a given initial state to a final state. Although evolutionary courses of these non Hamiltonian systems with two or more alternative ways of dissipation cannot be predicted, the flows of energy will search and naturally select paths of least action, known as geodesics, to consume free energy in the least time. The scale invariant natural patterns follow from this natural law that impinges on processes at all scales of space and time. PMID- 21030326 TI - Guerrillero Heroico--a lasting impression. AB - What once was simply a cultural tradition is fast becoming a popular phenomenon amongst Western tourists. Temporary henna tattoo designs performed by street or beach vendors are prevalent throughout the Middle East and Asia, particularly in holiday resorts. The public may be mistaken in thinking that the fashionable trend comes without significant risk. The main ingredient in the temporary tattooing method is henna (Lawsonia inermis), a flowering plant with dyeing properties that takes only several hours to be absorbed but provides an effect lasting around ten to fifteen days on the recipient's skin. The side effects of henna tattoos are well documented in the literature, although it is not clear whether the side effects directly relate to the henna ingredient or the additives used to prolong the designs. The most commonly noted complications include allergic contact dermatitis, infection, hypertrophic and keloid scarring and temporary or permanent hypo- or hyperpigmentation. In very rare cases, type 1 hypersensitivity reactions (angioedema and anaphylaxis) have been reported. The following case report highlights several of these complications and the relevant management. PMID- 21030327 TI - Optimizing diabetes care regarding cardiovascular targets at general practice level: Direct@GP. AB - AIMS: The objective of this study was to assess the adherence to national guidelines on cardiovascular (CV) prevention and target attainment for patients with type 2 diabetes mellitus followed-up in general practice. METHODS: Non interventional, cross-sectional survey. RESULTS: Type 2 diabetes patients remain undertreated with statins (63% treated), even so those with a cardiovascular history (80% treated). Although more patients received antihypertensive treatment (82%) compared to hypolipidemic medication (69%), the proportion of patients attaining targets for total cholesterol (TC) (35%), HDL-cholesterol (HDL-C) (65%), and LDL-cholesterol (LDL-C) (42%) exceeded far those attaining blood pressure control (13%). The primary endpoint of reaching the goal for LDL cholesterol (<100mg/dL; 2.59 mmol/L) was attained by 42% of patients, of which only 13% reached the more stringent target of LDL-C<70 mg/dL (1.81 mmol/L). About half of the patients (49%) attained glycemic control (HbA1c<7%) and 55% had triglycerides<150 mg/dL (1.69 mmol/L). CONCLUSIONS: The majority of type 2 diabetes patients are treated for hypercholesterolemia and hypertension, although, there is still under treatment, especially in patients with CV disease. Only 42% of patients were on target for LDL-cholesterol and 13% for blood pressure. Therefore, wider implementation of process and outcome indicators, which proved to be related, and continuous evaluation of their result, is needed. PMID- 21030328 TI - Cardiac troponin-I concentrations in dogs with bradyarrhythmias before and after artificial pacing. AB - OBJECTIVES: To quantify cardiac troponin-I (cTnI) concentration in dogs with symptomatic bradyarrhythmias before and after artificial pacing and to correlate cTnI concentration with diagnosis, echocardiographic parameters, serology, and outcome. ANIMALS, MATERIALS AND METHODS: Medical records from the University of Pennsylvania from 2006 to 2009 were reviewed, and 14 dogs with cTnI assay results before and after pacemaker were identified. The ECG diagnosis included complete atrioventricular block (AVB), sick sinus syndrome, 2nd degree AVB, and atrial standstill. Serology, presence of premature beats, echocardiographic measurements, and pacing modality were recorded. RESULTS: Mean cTnI concentration was elevated both pre- and post-pacing, and was significantly higher pre-pacing vs. post-pacing. Post-pacing cTnI concentration in 9 of 14 dogs (64%) remained above the reference range. Four dogs yielded high serum titers for Bartonella spp. Four dogs with markedly increased cTnI concentration had progressive left ventricular enlargement and myocardial failure as compared to pre-pacing examination. CONCLUSIONS: Elevated cTnI concentration suggests that cardiac injury persists after artificial pacing in dogs with bradyarrhythmias. Myocarditis secondary to Bartonella spp. or other causes may be an important cause of AVB in dogs. Prospective studies investigating the correlation of cTnI to potential etiology and development of post-pacing LV dysfunction and outcome are needed. PMID- 21030329 TI - Spine fracture in patient with ankylosing spondylitis: A case report. AB - Spinal fractures in patients with ankylosing spondylitis may be the result of minor trauma. These fractures may lead to severe neurological deficits, and they are difficult to detect using standard radiography. Often, CT-scans and MRI are required for diagnosis. PMID- 21030330 TI - Occupational and recreational physical activity during adult life and the risk of cancer among men. AB - BACKGROUND: There is a strong evidence for a protective role of physical activity (PA) on cancers of the colon, breast (postmenopausal) and endometrium, but data are less consistent or scarce for other cancer types. This study assessed the relationship between occupational and recreational PA and cancer risk among men in a population-based case-control study conducted in Montreal, Canada. METHODS: Incident cases of cancer of the lung (n=857), colon (n=496), bladder (n=484), prostate (n=449), stomach (n=251), rectum (n=248), non-Hodgkin's lymphoma (n=215), kidney (n=177), pancreas (n=116), melanoma (n=103), esophagus (n=99), Hodgkin's lymphoma (n=54), and 533 population controls, were interviewed. Detailed lifetime occupational PAs were translated into metabolic equivalents. Participation in sports and outdoor activities was elicited. RESULTS: Compared to those with low lifetime occupational PA levels, men with high occupational PA levels had decreased odds ratios (OR) for all cancer types. The strongest evidence was for cancers of the colon [OR: 0.58, 95% confidence interval (CI): 0.34-0.99] and the prostate (OR: 0.54, 95% CI: 0.31-0.95). Men engaging in sports and outdoor activities had lower risks of lung (OR: 0.69, 95% CI: 0.52-0.91), esophageal (OR: 0.54, 95% CI: 0.30-0.97) and bladder (OR: 0.78, 95% CI: 0.59 1.05) cancers, and somewhat increased risks of melanoma (OR: 1.24, 95% CI: 0.73 2.12). CONCLUSIONS: A protective effect of high lifetime occupational PA levels was observed for colon and prostate cancers. A tendency for inverse associations was also noted for several other cancer types. Recreational PA was inversely related with smoking-related cancers including lung, esophageal and bladder cancers. PMID- 21030331 TI - Morphological factors of mandibular edentulous alveolar ridges influencing the movement of dentures calculated using finite element analysis. AB - PURPOSE: The aim of this study was to determine the importance of each morphological factor of edentulous alveolar ridges according to its influence on the movement of complete dentures. METHODS: The shapes of casts and waxed complete dentures were digitized. The determined shapes of the ridges were uniformly divided circumferentially and radially. Principal component (PC) analysis was performed using the coordinates of the points on the grid as the variables (morphological PC). The denture movement under bilateral and unilateral loads was analyzed using a finite element (FE) model constructed from the digitized shape, following PC analysis of the displacement of representative points on the denture (displacement PC). The effects of the morphological PCs were evaluated by means of stepwise multiple regression analysis with displacement PC as a dependent variable. RESULTS: The ridge height, clearance between the ridge and the occlusal plane, and various inclinations, were significantly selected as independent variables where the dependent variable was the displacement PC under a bilateral load. Under a unilateral load, the displacement PC was mainly influenced by the ridge height. The influence of morphological PCs of the non-loaded side tended to be larger than that of loaded side. CONCLUSION: Under a bilateral load, ridge height, clearance to the occlusal plane, and inclination of the ridge are considered to account for denture movement. To evaluate the effect of the ridge morphology on denture movement under a unilateral load, it is effective to determine the partitioned shape together with the height in general. PMID- 21030332 TI - "Porcelain heart" cardiomyopathy secondary to hyperparathyroidism: radiographic, echocardiographic, and cardiac CT appearances. AB - We report the radiographic, echocardiographic and cardiac CT appearances of 'porcelain heart' in an 85-year-old woman who presented with progressive heart failure. The extensive myocardial calcification was secondary to hyperparathyroidism with renal failure. PMID- 21030333 TI - Pseudocoarction of the aorta and crossed fused ectopic kidney assessed by multidetector computed tomography. AB - Aortic pseudocoarctation is a congenital abnormality consisting of an elongated aortic arch with a kink at level of the isthmus. However, unlike coarctation, significant flow obstruction is not associated with pseudocoarctation, although there is an increased incidence other cardiovascular anomalies. This case demonstrates the use of multidetector CT as part of the clinical evaluation of a 49-year-old male with suspected aortic coarctation, leading to the final diagnosis of pseudocoarctation, as well as the incidental discovery of a crossed fused ectopic kidney. PMID- 21030334 TI - Periprocedural safety of 64-detector row coronary computed tomographic angiography: results from the prospective multicenter ACCURACY trial. AB - BACKGROUND: Coronary computed tomographic angiography (CCTA) requires iodinated contrast and often atrioventricular nodal blocking agents and nitroglycerin for heart rate lowering and coronary vasodilation, respectively. To date, the periprocedural safety of CCTA is unknown. OBJECTIVES: The purpose of this study was to evaluate the periprocedural safety of CCTA. METHODS: We prospectively evaluated 232 patients with symptomatic chest pain without preexisting renal insufficiency at 16 sites who underwent CCTA as part of the Assessment by Coronary Computed Tomographic Angiography of Individuals Undergoing Invasive Coronary Angiography (ACCURACY) trial. Patients received iodinated contrast, beta blockers, and nitroglycerin as part of a predefined CCTA protocol. We assessed the rates of adverse events (AEs) related to these agents. RESULTS: As measured by serum creatinine and creatinine clearance, no significant change was observed in renal function from baseline (1.00 +/- 0.19 mg/dL; modification of diet in renal disease [MDRD]: 76.91 +/- 17.96 mL/min/1.73 m(2)) to 48 hours (1.0 +/- 0.2 mg/dL; P = 1.00; MDRD change: 0.2 +/- 12.4 mL/min/1.73 m(2); P = 0.83) or at 30 days (1.0 +/- 0.2 mg/dL; P = 0.52; MDRD change: -0.9 +/- 16.9 mL/min/1.73 m(2); P = 0.77). Mean systolic blood pressure decreased from baseline (133 +/- 19 mm Hg) at 1 hour (125 +/- 17 mm Hg; P < 0.001) and rebounded at 48 hours (133 +/- 17 mm Hg). Mean heart rate decreased from baseline (65 +/- 10 beats/min) at 1 hour (60 +/- 7 beats/min) but rose at 48 hours (69 +/- 11 beats/min; P < 0.001. All patients were asymptomatic from baseline to follow-up. CONCLUSIONS: The performance of CCTA is safe with low rates of AEs. PMID- 21030335 TI - What is the optimal number of readers needed to achieve high diagnostic accuracy in coronary computed tomographic angiography? A comparison of alternate reader combinations. AB - BACKGROUND: Coronary computed tomographic angiography (CCTA) possesses high accuracy to detect coronary artery disease (CAD), although studies have reported differences in diagnostic performance. Prior trials used different numbers of interpreters, and the optimal number to detect CAD is unknown. OBJECTIVE: We compared the diagnostic performance of 1, 2, 3, and 5 randomly selected interpreters for CCTA. METHODS: We evaluated 50 patients randomly selected from 2 multicenter studies with both 64-detector CCTA and invasive quantitative coronary angiography (QCA). Five blinded, experienced readers independently interpreted CCTA and assessed for obstructive CAD (>= 50% stenosis) and high-risk CAD (left main, proximal left anterior descending, or 3-vessel stenoses). A core laboratory performed QCA. For each patient, different random combinations of readers were selected; the accuracy of 1, 2, and 5 readers was compared with 3 readers. RESULTS: Obstructive and high-risk CAD were observed in 20 of 50 (40%) and 6 of 50 (12%) patients, respectively. With combinations of 1, 2, 3, or 5 readers, there was a range of per-patient diagnostic performance (sensitivity, 100% each; specificity, 67%-90%; accuracy, 80%-94%; P = NS), per-segment diagnostic performance (sensitivity, 67%-83%; specificity, 87%-93%; accuracy, 87%-92%; P < .001 for 1 vs 3 and 2 vs 3 readers), and detection of high-risk CAD (sensitivity, 83%-100%; specificity, 73%-80%; accuracy, 76%-82%; P = NS). The highest diagnostic accuracy was observed with 3 readers for each comparison. CONCLUSION: The diagnostic performance of CCTA to detect obstructive or high-risk CAD is generally high irrespective of the number of readers. Consensus interpretation by >= 3 readers provides the highest diagnostic accuracy. PMID- 21030336 TI - Utility of recent studies to assess the National Research Council 2001 estimates of cancer risk from ingested arsenic. AB - OBJECTIVE: The purpose of this review is to evaluate the impact of recent epidemiologic literature on the National Research Council (NRC) assessment of the lung and bladder cancer risks from ingesting low concentrations (< 100 ug/L) of arsenic-contaminated water. DATA SOURCES, EXTRACTION, AND SYNTHESIS: PubMed was searched for epidemiologic studies pertinent to the lung and bladder cancer risk estimates from low-dose arsenic exposure. Articles published from 2001, the date of the NRC assessment, through September 2010 were included. Fourteen epidemiologic studies on lung and bladder cancer risk were identified as potentially useful for the analysis. CONCLUSIONS: Recent epidemiologic studies that have investigated the risk of lung and bladder cancer from low arsenic exposure are limited in their ability to detect the NRC estimates of excess risk because of sample size and less than lifetime exposure. Although the ecologic nature of the Taiwanese studies on which the NRC estimates are based present certain limitations, the data from these studies have particular strengths in that they describe lung and bladder cancer risks resulting from lifetime exposure in a large population and remain the best data on which to conduct quantitative risk assessment. Continued follow-up of a population in northeastern Taiwan, however, offers the best opportunity to improve the cancer risk assessment for arsenic in drinking water. Future studies of arsenic < 100 ug/L in drinking water and lung and bladder cancer should consider adequacy of the sample size, the synergistic relationship of arsenic and smoking, duration of arsenic exposure, age when exposure began and ended, and histologic subtype. PMID- 21030338 TI - Squamous cell carcinoma as a long-term effect of Tantalum-182 irradiation in childhood. PMID- 21030337 TI - Dose imprecision and resistance: free-choice medicated feeds in industrial food animal production in the United States. AB - BACKGROUND: Industrial food animal production employs many of the same antibiotics or classes of antibiotics that are used in human medicine. These drugs can be administered to food animals in the form of free-choice medicated feeds (FCMF), where animals choose how much feed to consume. Routine administration of these drugs to livestock selects for microorganisms that are resistant to medications critical to the treatment of clinical infections in humans. OBJECTIVES: In this commentary, we discuss the history of medicated feeds, the nature of FCMF use with regard to dose delivery, and U.S. policies that address antimicrobial drug use in food animals. DISCUSSION: FCMF makes delivering a predictable, accurate, and intended dose difficult. Overdosing can lead to animal toxicity; underdosing or inconsistent dosing can result in a failure to resolve animal diseases and in the development of antimicrobial resistant microorganisms. CONCLUSIONS: The delivery of antibiotics to food animals for reasons other than the treatment of clinically diagnosed disease, especially via free-choice feeding methods, should be reconsidered. PMID- 21030339 TI - Erythema nodosum: etiological factors and relapses in a retrospective cohort study. AB - Erythema nodosum (EN) is a septal panniculitis which may be associated with a wide variety of factors and disorders. In some patients it is recurrent, but few studies have considered recurrent EN. Our aim was to describe the causes of and diseases associated with EN and relapsing EN. Patients diagnosed with EN from 1997 to 2007 were included. EN was defined as post-infective, based on temporal, clinical, laboratory and microbiological criteria. Diagnosis of drug-induced EN was based on a temporal correlation, on the relapse of EN after drug re introduction and on the absence of relapsing EN with a continuous treatment with the imputed drug. When the above criteria were excluded and EN was not associated with an underlying systemic disease or pregnancy, it was considered idiopathic.124 patients (mean age 39.5 years; median 37 years; range 4-90 years) were visited and re-evaluated after one to ten years (mean +/- SD follow up time 5 +/- 4 years). In 73 (58.8%) patients an aetiology of the first manifestation of EN was attributed to infections (25.8% of the total number; 32% of those with an attributed aetiology), drugs (mostly sex hormones; 15.3%; 26%), systemic diseases (11.2%; 19.2%) and pregnancy (6.5%; 10.9%). EN relapsed in 33 (26.6%) patients and was mostly attributed to infections and drugs. Factors responsible for the first manifestation of EN frequently differed from those causing relapses in the same patients, with the exception of drug-induced EN. We conclude that drug induced EN can recur after re-exposure to the same drug, and the recurrence can be predicted. PMID- 21030340 TI - Lupus erythematosus tumidus: clinical, histopathological and serological aspects and therapy response of 21 patients. AB - Twenty-one Caucasian patients (12 women and 9 men) were diagnosed as having lupus erythematosus tumidus by clinical and histopathological criteria. They were analysed by blood tests, histopathology and immunological studies and their response to treatment was recorded. While blood tests yielded non contributory results, histopathology showed in all cases a superficial and deep lymphocytic infiltrate with a perivascular and periadnexal involvement and an interstitial dermal deposition of mucin. Minimal epidermal changes were observed in 13 cases. In particular, epidermal atrophy was found in 8 specimens, hyperkeratosis in 8, parakeratosis in 2, acanthosis in 3 and spongiosis in 1. Four patients showed a slight vacuolar degeneration and periodic acid-Schiff staining showed a thickened basal membrane zone in two. Direct immunofluorescence was positive in 16 of the 19 patients tested. Antinuclear antibodies were negative in all 21 patients in indirect immunofluorescence. Antimalarials cleared the lesions within 12 weeks in 16 patients. Fourteen of them relapsed about 3 weeks after the first sun exposure, but were successfully controlled with the same treatment within a maximum of 12 weeks. Spontaneous resolution of the skin lesions was never observed. Altogether, some evidence of heterogeneity is suggested, some cases strictly satisfying Kuhn et al's criteria, others resembling discoid lupus more closely. PMID- 21030341 TI - Hypnopompic seizures. AB - The relationship between epilepsy and sleep is complex and bidirectional. Ictal awakening is probably a common and well-described phenomenon. In this small observational study we describe arousal from sleep as the only, or at least main, manifestation of some epileptic seizures. We coin the term "hypnopompic seizures" to describe this entity. Five patients with intractable epilepsy were monitored by continuous video-electroencephalogram. Four of them had left temporal lobe epilepsy and one patient had generalised epilepsy. Hypnopompic seizures accounted for 30-100% of their seizure types captured during monitoring. All the seizures occurred during stage II sleep and were brief. Hypnopompic seizures are extremely subtle and may be underdiagnosed and underreported. Future larger studies are needed to shed some light on this unique entity and its neuropathophysiology. Epileptologists should be aware of this type of seizure and careful review of electroencephalograms during the transition from sleep to arousal is imperative to capture these seizures. Physicians, patients and families also need to be aware of such a subtle manifestation of seizures. Improved awareness of hypnopompic seizures and subtle seizures, in general, help guide accurate and early diagnosis, thorough monitoring and appropriate management. PMID- 21030343 TI - Fcgamma receptor predictive genomic testing and the treatment of indolent non Hodgkin lymphoma. PMID- 21030344 TI - The annual meeting of the American Society of Clinical Oncology. June 4-8, 2010; Chicago, IL. PMID- 21030345 TI - Uncommon or delayed adverse events associated with imatinib treatment for chronic myeloid leukemia. AB - Imatinib, a tyrosine kinase inhibitor, is the first-line therapy for chronic myeloid leukemia (CML). The majority of patients continue treatment for their lifespan because discontinuation generally results in relapse. Many patients treated with imatinib experience adverse events (AEs) at some time during their treatment. Commonly encountered AEs and their management are well known. However, in addition to the common AEs with imatinib, there is a significant number of patients who display either uncommon or delayed AEs. These events can involve cardiac, renal, or dermatologic problems, and fluid retention. Herein, we review these less-than-common side effects and the hazard of administering imatinib during pregnancy. While chronic treatment with imatinib has revolutionized CML prognosis, physicians should be aware of both the common and uncommon adverse reactions. PMID- 21030346 TI - Management of mantle cell lymphoma: key challenges and next steps. AB - Mantle cell lymphoma (MCL) is regarded as an aggressive lymphoid malignancy that exhibits varied clinical behavior and prognoses, reflecting the biologic heterogeneity of the disease. In most cases, patients with MCL achieve a shorter median survival compared with more common B-cell lymphomas, such as follicular lymphoma, and are less likely to achieve a durable response with chemotherapy. Currently, there is no defined standard of care for patients with MCL. Rituximab containing immunochemotherapy strategies are commonly used, but the addition of rituximab to conventional induction chemotherapy has produced suboptimal responses that are relatively short-lived and have not resulted in a survival advantage. Further intensification of the chemotherapy component, including autologous stem cell transplantation, has increased response and survival rates but has not proven to be curative while being associated with higher toxicity. Clearly, there is a need for developing novel agents and strategies that will improve clinical outcomes for patients with MCL. Targeted therapies and new cytotoxic agents are showing great promise and may have a role in maintenance and/or initial therapy. This summary highlights current challenges in the management of MCL, and outlines expert perspectives, key questions, and future directions. For the third consecutive year, a panel of global experts in MCL assembled to deliberate on topical issues in MCL including advances in pathobiology, strategies for risk-adapted therapy, front-line treatment options, consolidation approaches, and novel therapeutic strategies. The proceedings of this workshop, held December 3, 2009 in New Orleans, LA, are summarized here. It must be emphasized that this synopsis is not meant to serve as an exhaustive review of MCL biology and management, but is a distillation of the expert discussions, highlighting key questions and future directions identified. PMID- 21030347 TI - Fcgamma receptor polymorphisms and clinical efficacy of rituximab in non-Hodgkin lymphoma and chronic lymphocytic leukemia. AB - It has been 40 years since the discovery of Fcgamma receptors (FcgammaRs) and their function. FcgammaRs regulate a variety of immune responses, including phagocytosis, degranulation, antibody-dependent cellular cytotoxicity, transcriptional regulation of cytokines, chemokine expression, B-cell activation, and immune complex clearance. It is well known that FcgammaRs serve as a critical link between the humoral and cellular branches of the immune system and play an important role in many conditions, including infection, cancer, and autoimmune diseases. Recent studies suggest that FcgammaR polymorphisms influence efficacy and side effects of monoclonal antibody-based immunotherapy, which might provide a useful prognostic marker for treatment in the future. Rituximab has been proven effective in treating patients with non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Some FcgammaR genotypes correlate with rituximab efficacy in patients with NHL but not in patients with CLL. In this review, FcgammaR function and the association between FcgammaR polymorphisms and rituximab efficacy in NHL and CLL are discussed. PMID- 21030348 TI - Outcome and toxicity in the modern era of new drugs for multiple myeloma: a reappraisal for comparison with future investigational trials. AB - The introduction of new drugs such as thalidomide, lenalidomide, and bortezomib has led to novel treatment strategies and significantly improved the outcome of patients with multiple myeloma (MM). The enhanced knowledge of myeloma pathogenesis has allowed the identification of new therapeutic targets and many clinical trials are either planned or in progress to evaluate these more selective drugs in the near future. The results of these studies, however, will have to be compared with the results of existing novel therapies for the treatment of MM in order to define whether new protocols do not duplicate current new standards and constitute a real improvement. We reviewed the results of a series of phase I, II, III studies with thalidomide, lenalidomide, and bortezomib combinations for newly diagnosed MM in order to define a reasonable standard in terms of activity, efficacy, and toxicity and to have a potentially useful starting point for comparisons with future investigational trials. Three-drug regimens appear to double the complete remission (CR) rate (20%), though regimens containing 4 drugs triple the CR rate (30%), compared with those containing only 2 agents (10%). These improvements in the depth and quality of response translate into a progressive increase in the progression-free survival rate at 2 years (from approximately 54%-62% to 75%, respectively). Conversely, by using additional agents, a marked increase in hematologic toxicity has been described (8%, 28%, and 28% respectively), whereas nonhematologic toxicity appears to be similar (26%, 24%, and 27%, respectively). These results suggest that new trials in the future will constitute significant progress if they can improve on the current relatively favorable efficacy/toxicity ratio. Nonetheless, exciting new combinations in development do hold promise and results from these studies are eagerly awaited. PMID- 21030349 TI - Ofatumumab: a new CD20 monoclonal antibody therapy for B-cell chronic lymphocytic leukemia. AB - Though most patients with chronic lymphocytic leukemia (CLL) respond to first line therapy, all patients eventually relapse, after which therapeutic options are limited. Fludarabine-refractory patients have a particularly poor prognosis. The addition of the CD20 monoclonal antibody (MoAb) rituximab to chemotherapy in CLL has improved outcomes, particularly in early lines of therapy; however, the efficacy of rituximab monotherapy in CLL is limited, potentially in part because of reduced cell lysis via complement-dependent cytotoxicity (CDC) in this setting. Rituximab CDC is dependent on CD20 expression; CLL cells underexpress CD20. Ofatumumab is a human MoAb that targets an epitope encompassing the membrane-proximal small-loop on the CD20 molecule, which differs from the binding location of rituximab. In vitro studies with ofatumumab have demonstrated that it is significantly more effective than rituximab at corresponding dose levels at lysing CLL cells and B-cell lines, especially those with low CD20 copy numbers. In patients with CLL refractory to both fludarabine and alemtuzumab or refractory to fludarabine with bulky lymphadenopathy and, therefore, less suitable for treatment with the CD52 MoAb alemtuzumab, results from the planned interim analysis showed an encouraging response rate with ofatumumab (Independent Endpoint Review Committee evaluated) and survival parameters, which seemed to be higher than those reported from a historical assessment of other salvage therapies in a corresponding group of patients. Ofatumumab was also well tolerated; the most common adverse events were transient grade 1 or 2 infusion reactions and infections. Ongoing trials will help confirm the role of ofatumumab in CLL, in addition to the effect of this agent in combination with chemotherapies and other MoAbs. PMID- 21030350 TI - Chronic lymphocytic leukemia: new concepts for future therapy. AB - Over the past several years, we have witnessed rapid advances in our understanding of the biology and treatment of chronic lymphocytic leukemia (CLL). New prognostic factors have been characterized that help identify patients at high risk of rapid disease progression, refractoriness to treatment, and short overall survival (OS). These advances have led to a significant paradigm shift in the management of CLL. Novel therapeutic strategies, including combinations of monoclonal antibodies with conventional chemotherapy, have dramatically improved response rates, remission duration, and recently, OS. However, these benefits do not appear to extend to certain patient subsets, especially those with unfavorable clinical or cytogenetic risk factors. The majority of patients with CLL will invariably relapse following first-line therapy and can acquire high risk genetic abnormalities. Repeated treatment leads to eventual therapeutic refractoriness and shortened survival compared with age-matched healthy individuals. Several novel agents and strategies, including next-generation anti CD20 monoclonal antibodies, the alkylating agent bendamustine, the immunomodulatory agent lenalidomide, the cyclin-dependent kinase inhibitor flavopiridol, and small-molecule Bcl2 inhibitors, are currently under clinical investigation as novel agents that will hopefully improve treatment outcomes for CLL. Though allogeneic stem cell transplantation offers curative potential, it also presents clinical challenges in terms of patient appropriateness, donor availability, and timing. The merits and challenges of incorporating these treatment modalities into the treatment algorithm for patients with CLL, as discussed by a panel of experts in CLL, are outlined in this article. PMID- 21030351 TI - Rituximab and CHOP chemotherapy plus GM-CSF for previously untreated diffuse large B-cell lymphoma in the elderly: a Wisconsin oncology network study. AB - PURPOSE: Human recombinant granulocyte-macrophage colony-stimulating factor (GM CSF) may potentiate rituximab activity by upregulating CD20 expression and activating effector cells necessary for antibody-dependent cellular cytotoxicity. GM-CSF was combined with standard rituximab + CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone) chemotherapy (R-CHOP) in the treatment of elderly patients with de novo diffuse large B-cell lymphoma (DLBCL). PATIENTS AND METHODS: Thirty-eight patients over the age of 60 years with newly diagnosed DLBCL were treated with R-CHOP every 21 days for 6-8 cycles and GM-CSF 250 ug/m2 per day on days 3-10. Patients were evaluated for response after cycles 4, 6, and 8. The primary endpoint was the rate of complete response, and secondary endpoints were progression-free survival (PFS), event-free survival, and overall survival (OS). RESULTS: Thirty-eight patients were enrolled, with a median age of 72 years, and 29% of patients having high-risk disease (International Prognostic Index [IPI] score >= 4). A complete or unconfirmed complete response (CR) was achieved in 53% of patients. After a median follow-up of 51.1 months, the 3-year PFS and OS were 78% and 84%. Twenty one percent of patients discontinued protocol treatment because of chemotherapy related toxicity and 16% because of GM-CSF toxicity. Dose intensity for planned chemotherapy cycles was 81.1%. CONCLUSION: These data suggest that survival outcomes may be modestly improved when GM-CSF is combined with R-CHOP in the treatment of elderly DLBCL. GM-CSF had toxicity precluding planned administration in 16% of patients, which may limit usefulness of this agent. Further investigation of GM-CSF in combination with rituximab-containing chemotherapy is warranted. PMID- 21030352 TI - Elevated expression of APE1/Ref-1 and its regulation on IL-6 and IL-8 in bone marrow stromal cells of multiple myeloma. AB - A number of growth factors secreted by bone marrow stromal cells (BMSCs), including interleukin-6 and -8 (IL-6/8), are important for the initiation and progression of multiple myeloma (MM). However, the mechanisms that regulate the production of IL-6/8 by BMSC have not yet been well characterized. Human dual functional protein apurinic/apyrimidinic endonuclease-1/redox factor-1 (APE1/Ref 1) is essential for cell survival and proliferation. Previous studies showed that APE1/Ref-1 was overexpressed in tumor cells, but few studies showed its expression in supportive cells in the tumor microenvironment. We first detected APE1/Ref-1 expression in BMSCs of normal, initial, and recurrent MM patients, and then explore the correlation between APE1/Ref-1 level and IL-6/8 secretion of BMSCs. A marked increase of APE1/Ref-1 expression and abnormal subcellular distribution were observed in MM BMSCs. APE1/Ref-1 overexpression was related to higher secretary level of IL-6/8 by MM BMSCs and the IL-6/8 secretion was blocked significantly by adenovirus-mediated APE1/Ref-1-specific (small interfering RNA) siRNA. Our results also demonstrated that APE1/Ref-1-specific siRNA significantly inhibited DNA binding activity of AP-1 and nuclear factor-kappaB (NF-kappaB), 2 important transcription factors in the regulation IL-6/8 secretion in MM BMSCs. The results provided by the present study indicate APE1/Ref-1, which plays a regulatory role in IL-6/8 production by BMSCs, may be a potential therapeutic target of MM. PMID- 21030353 TI - The durable clearance of the T315I BCR-ABL mutated clone in chronic phase chronic myelogenous leukemia patients on omacetaxine allows tyrosine kinase inhibitor rechallenge. AB - PURPOSE: The onset of a BCR-ABLT315I mutation during the course of chronic myelogenous leukemia (CML) on tyrosine kinase inhibitors (TKIs) usually results in poor survival, and therapeutic options remain few in the absence of any allogeneic donor. PATIENTS AND METHODS: We have investigated the affect of subcutaneous omacetaxine (OMA, or homo-harringtonine) cycles on unmutated and T315I-mutated BCR-ABL transcripts in a series of 8 TKI-resistant chronic-phase CML patients and we have addressed the question of whether the administration of OMA could resensitize patients to TKIs. Patients were regularly monitored for total disease burden and for BCR-ABLT315I transcripts using a new quantitative sensitive technique (sensitivity threshold, 0.05%), for up to 27 cycles of OMA. RESULTS: Overall, patients demonstrated hematologic, cytogenetic, or molecular improvement. An initial rapid decline and a sustained disappearance of T315I mutated transcripts were observed in 50% of patients, after a median of 10.5 cycles (range, 3-27 cycles) of OMA. As the unmutated leukemic burden reduction was modest, 2 patients were submitted to nilotinib after 9 months of sustained BCR-ABLT315I transcripts negativity on OMA and mutated transcripts remained undetectable after a median follow-up of 12 months on nilotinib challenge. CONCLUSION: We suggest that OMA (ie, a non-targeted therapy) might provide a better disease control allowing the disappearance of the mutated clone probably elicited by the clone deselection after TKI release, and/or a preferential activity of OMA on the T315I-mutated cells through unknown mechanisms. These observations suggest that OMA could allow a safe TKI rechallenge in patients with resistant chronic-phase CML. PMID- 21030355 TI - New drug update: 2010. AB - Five new drugs that are used for medical problems often encountered in the elderly have been selected for consideration in this review. The uses and most important properties of these agents are considered, and a rating for each new drug is determined using the New Drug Comparison Rating (NDCR) system developed by the author. In the NDCR system, a rating from 1 to 5 (5 being the highest rating) is assigned for each new drug. The rating is based on a comparison of the new drug with related drugs already marketed. Advantages, disadvantages, and other important information regarding the new drug are identified and used as the basis for determining the rating. PMID- 21030356 TI - 2010-2011 ASCP president Al Barber: a man for all settings. AB - Next month, Albert R. Barber, PharmD, CGP, FASCP, becomes the president of the American Society of Consultant Pharmacists for 2010-2011. What distinguishes his career is his wide-ranging experience in almost every pharmacy setting: retail, long-term care pharmacy, independent consultant pharmacist, clinical administrator for a large health care company. His goals as president are to directly involve more ASCP members and to reach out to pharmacists serving seniors beyond the nursing facility setting. PMID- 21030357 TI - Survey of bisphosphonate regimen preferences in an urban community health center. AB - OBJECTIVE: to determine patient preference for bisphosphonate therapy based on dosage form and dosing schedule. DESIGN: prospective telephone survey. SETTING: urban community health center. PATIENTS, PARTICIPANTS: all patients who were seen in the osteoporosis clinic during the 22-month time period were contacted. Patients were excluded if they could not complete the survey in English, had difficulty hearing, had cognitive impairment, or were unable to be reached by telephone. INTERVENTIONS: patients were asked which route and frequency of bisphosphonate therapy was preferred, convenient, and easiest to remember. MAIN OUTCOME MEASURE(S): patient-reported preference for route and frequency of bisphosphonate administration. RESULTS: ninety patients were included in the final analysis. Preference for bisphosphonate therapy illustrated that equal numbers of respondents preferred either once-monthly or once-yearly regimens (24.4% for each, n = 22). One-third of respondents (n = 30) indicated that a once yearly infusion was the most convenient method of administration. The survey revealed no strong association of which regimen was easiest to remember. CONCLUSION: the majority of patients preferred once-monthly or less frequent dosing schedules. Clinicians may consider discussing patient preferences during initiation and throughout therapy. PMID- 21030358 TI - Quetiapine for sleep in patients with dementia. AB - OBJECTIVE: to examine the use of quetiapine for sleep in patients with dementia admitted to a geriatric psychiatry ward. DESIGN: retrospective cross-sectional study (January 2007 to December 2009). SETTING: geriatric psychiatric unit located near a metropolitan city in North Carolina. PARTICIPANTS: all patients admitted with a diagnosis of dementia who were also receiving quetiapine were eligible. One hundred one patients met the criteria and were included in the study. INTERVENTION: none. MAIN OUTCOME MEASURES: descriptive statistics defining quetiapine prescribing. Based on a priori criteria, quetiapine was considered to be used for sleep if it were prescribed: 1) only at bedtime, as needed, for sleep, 2) once daily, only at bedtime, or 3) multiple times daily, but with at least 75% of the daily dose administered at bedtime. RESULTS: forty-three of the 101 patients included in the study were prescribed quetiapine, probably for sleep. Quetiapine, when used as a sedative-hypnotic, was generally employed at doses between 50 mg and 100 mg nightly. Several published studies report beneficial sleep-promoting effects of quetiapine and other atypical antipsychotics for primary and secondary sleep complaints; however, most of these trials involve young and middle-aged adults, have diagnostic variability, and are limited methodologically. CONCLUSION: quetiapine prescribed as a sedative hypnotic in patients with dementia, while common, is understudied and not without risk. PMID- 21030359 TI - The goal blood pressure in type 2 diabetes: do we have an ACCORD? PMID- 21030360 TI - Preservation of beta-cell function in type 2 diabetes. AB - OBJECTIVE: To review available data on preservation and potential improvement of beta-cell function in patients with type 2 diabetes mellitus (T2DM) with use of currently available strategies and agents. METHODS: Using key words, we performed a MEDLINE search of the relevant literature published through 2009 regarding the effects of available agents on beta-cell function in humans with T2DM. RESULTS: On the basis of current clinical data, no uniformly effective treatment for beta cell preservation has been found. Lifestyle intervention and early intensive insulin therapy appear to have some preservative properties on beta-cell function. Glucagonlike peptide-1 agonists, dipeptidyl- peptidase-4 inhibitors, and thiazolidinediones result in maintenance and often improvement of beta-cell function during their active use; however, data on their ability to preserve beta cell function when patients are not receiving active treatment are limited. CONCLUSION: The continuous loss of beta-cell mass and beta-cell function is a critical mechanism underlying the progressive deterioration of glycemic control in T2DM. In light of the projected increase in individuals at risk for developing T2DM, strategies and agents aimed at delaying or preventing the progression and inducing a remission of the disease are needed. Future research on this topic should include comparative efficacy trials with washout periods incorporating currently available and novel medications and strategies for preservation of beta cells. PMID- 21030361 TI - Low maternal exposure to ultraviolet radiation in pregnancy, month of birth, and risk of multiple sclerosis in offspring: longitudinal analysis. AB - OBJECTIVES: To investigate the distribution of month of birth in people with multiple sclerosis in Australia. To use the large regional and seasonal variation in ambient ultraviolet radiation in Australia to explore the association between exposure to ultraviolet radiation during pregnancy and subsequent risk of multiple sclerosis in offspring. DESIGN: Data were gathered on birth month and year (1920-1950), sex, and state of birth for all patients surveyed in 1981 in Queensland, Western Australia, New South Wales (including Australian Capital Territory), South Australia, and Hobart (Tasmania). Population denominators were derived from the 1981 census and supplementary birth registration data. A variable for exposure to ambient ultraviolet radiation "at birth" was generated from monthly averages of daily total ambient ultraviolet radiation for each region. Negative binomial regression models were used to investigate exposure to ambient ultraviolet radiation at birth and at various intervals before birth. SETTING: Patient data from multiple sclerosis prevalence surveys carried out in 1981; 1981 Australian census (giving the total number of people born in Australia and still alive and living in Australia in 1981 by year of birth 1920-50); supplementary Australian birth registration data covering the same birth years by month and state. PARTICIPANTS: 1524 patients with multiple sclerosis born in Australia 1920-50 from total population of 2 468 779. MAIN OUTCOME MEASURE: Cumulative incidence rate of multiple sclerosis. RESULTS: There was a pattern of risk of multiple sclerosis with month of birth (adjusted incidence rate ratio 1.32, 95% confidence interval 1.10 to 1.58, P<0.01, for those born in November December compared with those born in May-June). This pattern mirrored that previously reported in the northern hemisphere. Region of birth was related to risk. After adjustment for region of birth and other factors, there was an inverse association between ambient ultraviolet radiation in the first trimester and risk of multiple sclerosis (with >=25 erythemal (skin reddening) dose units as reference (that is, adjusted incidence rate ratio=1.00), the rates were 1.54 (1.10 to 2.16) for 20-<25 units; 1.58 (1.12 to 2.22) for 15-<20 units; 1.65 (1.17 to 2.33) for 10-<15 units; 1.65 (1.18 to 2.29) for 5-<10 units; and 1.67 (1.18 to 2.37) for <5 units). After adjustment for this exposure during early pregnancy, there was no residual association between month of birth and multiple sclerosis. CONCLUSION: Region of birth and low maternal exposure to ultraviolet radiation in the first trimester are independently associated with subsequent risk of multiple sclerosis in offspring in Australia. PMID- 21030363 TI - Recurrence of hyperemesis across generations. PMID- 21030362 TI - Recurrence of hyperemesis gravidarum across generations: population based cohort study. AB - OBJECTIVE: To estimate the risk of hyperemesis gravidarum (hyperemesis) according to whether the daughters and sons under study were born after pregnancies complicated by hyperemesis. DESIGN: Population based cohort study. SETTING: Registry data from Norway. PARTICIPANTS: Linked generational data from the medical birth registry of Norway (1967-2006): 544 087 units of mother and childbearing daughter and 399 777 units of mother and child producing son. MAIN OUTCOME MEASURE: Hyperemesis in daughters in mother and childbearing daughter units and hyperemesis in female partners of sons in mother and child producing son units. RESULTS: Daughters who were born after a pregnancy complicated by hyperemesis had a 3% risk of having hyperemesis in their own pregnancy, while women who were born after an unaffected pregnancy had a risk of 1.1% (unadjusted odds ratio 2.9, 95% confidence interval 2.4 to 3.6). Female partners of sons who were born after pregnancies complicated by hyperemesis had a risk of 1.2% (1.0, 0.7 to 1.6). Daughters born after a pregnancy not complicated by hyperemesis had an increased risk of the condition if the mother had hyperemesis in a previous or subsequent pregnancy (3.2 (1.6 to 6.4) if hyperemesis had occurred in one of the mother's previous pregnancies and 3.7 (1.5 to 9.1) if it had occurred in a later pregnancy). Adjustment for maternal age at childbirth, period of birth, and parity did not change the estimates. Restrictions to firstborns did not influence the results. CONCLUSIONS: Hyperemesis gravidarum is more strongly influenced by the maternal genotype than the fetal genotype, though environmental influences along the maternal line cannot be excluded as contributing factors. PMID- 21030364 TI - Cohort study to test the predictability of the Melbourne criteria for activation of the medical emergency team. AB - OBJECTIVE: To test the predictability of the Melbourne criteria for activation of the medical emergency team (MET) to identify children at risk of developing critical illness. DESIGN: Cohort study. SETTING: Admissions to all paediatric wards at the University Hospital of Wales. OUTCOME MEASURES: Paediatric high dependency unit admission, paediatric intensive care unit admission and death. RESULTS: Data were collected on 1000 patients. A single abnormal observation determined by the Melbourne Activation Criteria (MAC) had a sensitivity of 68.3% (95% CI 57.7 to 77.3), specificity 83.2% (95% CI 83.1 to 83.2), positive predictive value (PPV) 3.6% (95% CI 3.0 to 4.0) and negative predictive value 99.7% (95% CI 99.5 to 99.8) for an adverse outcome. Seven of the 16 children (43.8%) would not have transgressed the MAC prior to the adverse outcomes. Four hundred and sixty-nine of the 984 children (47.7%) who did not have an adverse outcome would have transgressed the MAC at least once during the admission. CONCLUSION: The MAC has a low PPV and its full implementation would result in a large number of false positive triggers. Further research is required to determine the relative contribution of the components of this complex intervention (Paediatric Early Warning System, education and MET) on patient outcome. PMID- 21030366 TI - General anaesthesia or sedation for paediatric neuroimaging: current practice in a teaching hospital. PMID- 21030365 TI - Intranasal lidocaine and midazolam for procedural sedation in children. AB - OBJECTIVE: To evaluate the safety and efficacy of a sedation protocol based on intranasal lidocaine spray and midazolam (INM) in children who are anxious and uncooperative when undergoing minor painful or diagnostic procedures, such as peripheral line insertion, venipuncture, intramuscular injection, echocardiogram, CT scan, audiometry testing and dental examination and extractions. PATIENTS AND DESIGN: 46 children, aged 5-50 months, received INM (0.5 mg/kg) via a mucosal atomiser device. To avoid any nasal discomfort a puff of lidocaine spray (10 mg/puff) was administered before INM. The child's degree of sedation was scored using a modified Ramsay sedation scale. A questionnaire was designed to evaluate the parents' and doctors' opinions on the efficacy of the sedation. Statistical analysis was used to compare sedation times with children's age and weight. RESULTS: The degree of sedation achieved by INM enabled all procedures to be completed without additional drugs. Premedication with lidocaine spray prevented any nasal discomfort related to the INM. The mean duration of sedation was 23.1 min. The depth of sedation was 1 on the modified Ramsay scale. The questionnaire revealed high levels of satisfaction by both doctors and parents. Sedation start and end times were significantly correlated with age only. No side effects were recorded in the cohort of children studied. CONCLUSIONS: This study has shown that the combined use of lidocaine spray and atomised INM appears to be a safe and effective method to achieve short-term sedation in children to facilitate medical care and procedures. PMID- 21030367 TI - Trial of Therapeutic Assessment in London: randomised controlled trial of Therapeutic Assessment versus standard psychosocial assessment in adolescents presenting with self-harm. AB - OBJECTIVE: To determine whether Therapeutic Assessment (TA) versus assessment as usual (AAU) improves engagement with follow-up in adolescents presenting with self-harm. DESIGN: Randomised controlled trial with 3 months naturalistic follow up. SETTING: Child and adolescent mental health services in two London National Health Service Trusts. PARTICIPANTS: 26 clinicians randomised into TA and AAU groups recruited 70 newly referred adolescents with self-harm. INTERVENTIONS: TA, a manualised procedure including a basic psychosocial assessment and a 30 min therapeutic intervention; AAU, standard psychosocial assessment. MAIN OUTCOME MEASURES: Attendance at the first follow-up session; number of the follow-up sessions attended and changes in Strengths and Difficulties Questionnaire and Children's Global Assessment Scale scores. All measures were adjusted for clustering, social class, changes of therapist and previous contact with services. RESULTS: Using the data on all participants (n=70), those in the TA group were significantly more likely to attend the first follow-up appointment: 29 (83%) versus 17 (49%), OR 5.12, 95% CI (1.49 to 17.55) and more likely to attend four or more treatment sessions: 14 (40%) versus 4 (11%), OR 5.19, 95% CI (2.22 to 12.10). Three months after the initial assessment there were no statistically significant differences between the groups on Strengths and Difficulties Questionnaire scores: 15.6 versus 16.0, mean difference -0.37, 95% CI (-3.28 to 2.53) or Children's Global Assessment Scale scores: 64.6 versus 60.1, mean difference 4.49, 95% CI (-0.98 to 9.96). CONCLUSIONS: TA was associated with statistically significant improvement in engagement. TA could be usefully applied at the point of initial assessment for adolescents with self harm. TRIAL REGISTRATION: ISRCTN 81605131 http://www.controlled trials.com/ISRCTN81605131/. PMID- 21030368 TI - Safety of formoterol in children and adolescents: experience from asthma clinical trials. AB - BACKGROUND: The safety of long-acting beta(2) agonist (LABA) therapy in asthma remains controversial but no large scale analyses have been published of LABA safety in children. METHODS: The frequency of asthma-related deaths and hospitalisations following formoterol use in children (4-11 years) and adolescents (12-17 years), compared with non-LABA treatment, was assessed in all AstraZeneca-sponsored, randomised, controlled, parallel-group trials (>=3 months) where formoterol was used as maintenance and/or as reliever therapy. RESULTS: 11,849 children and adolescents under the age of 18 years from 41 trials were identified, 82% of whom used an inhaled corticosteroid (ICS) as concomitant medication. The number of asthma-related deaths (one 13-year-old boy among 7796 formoterol-treated patients, and none among 4053 non-LABA-treated patients) was too low to allow any between-group comparison. The frequency of patients with asthma-related hospitalisations was not different in formoterol-treated versus non-LABA-treated patients, either in children (1.16% (38/3263) vs 1.11% (24/2165)) or in adolescents (0.51% (23/4533) vs 0.85% (16/1888)). Asthma-related hospitalisations based on daily dose of formoterol were: (A) 4.5 or 9 ug: 1.9% (18/980); (B) 18 ug: 0.5% (14/2870); (C) 36 ug: 0% (0/67); and (D) variable dosing: 0.75% (29/3879). There was no difference between formoterol-treated and non-LABA-treated patients as regards ethnicity. CONCLUSIONS: Formoterol use in children and adolescents (4-17 years) with asthma in this large study where the majority are prescribed concomitant ICS is not associated with any increased risk of asthma-related hospitalisations. The results are not influenced by dose or ethnicity. PMID- 21030370 TI - Demand for paediatric allergy services is high. PMID- 21030369 TI - Assessment of liquid captopril formulations used in children. AB - OBJECTIVE: Unlicensed liquid captopril formulations are commonly used to treat children with heart disease. This study assessed the bioequivalence of two liquid preparations against a licensed tablet form. DESIGN: An open label, single dose, three-treatment, three-period, crossover trial. SETTING: Outpatient. PATIENTS: Healthy adult volunteers (n=18). INTERVENTIONS: Each subject was randomly assigned to one of six dosing sequences, and dosed with 25 mg captopril on each of three dosing visits separated by a washout of at least 14 days. Blood samples for pharmacokinetic analysis were taken at regular intervals (0 min to 10 h) post dose. MAIN OUTCOME MEASURES: Bioequivalence of the formulations would be concluded if the 90% CI for the estimated ratio of the means of C(max) (maximum plasma concentrations) and area under curve(AUC) (extent of absorption) lay entirely within the range 0.8 to 1.25 RESULTS: Both liquid formulations failed the bioequivalence assessment with respect to C(max) and AUC. The 90% CI of the mean ratios of liquid/licensed tablet for both C(max) and AUC, fell outside the 0.8 to 1.25 limits. There was also considerable within-subject variability in C(max) (97.5%) and AUC (78.5%). CONCLUSIONS: Unlicensed captopril formulations are not bioequivalent to the licensed tablet form, or to each other, and so cannot be assumed to behave similarly in therapeutic use. Thus formulation substitution must be done with care and may require a period of increased monitoring of the patient. There is also significant within-subject variability in performance which has clinical implications with respect to titrating to an optimum therapeutic dose. PMID- 21030372 TI - Screening for autism in preterm children: diagnostic utility of the Social Communication Questionnaire. AB - OBJECTIVE: Preterm survivors are at high risk for autism spectrum disorders (ASD). The diagnostic utility of the Social Communication Questionnaire (SCQ) in screening for ASD was assessed in extremely preterm children at 11 years of age. DESIGN: All babies born at <26 weeks gestation in UK and Ireland from March through December 1995 were recruited to the EPICure Study. Of 307 survivors, 219 (71%) were assessed at 11 years. Parents of 173 children completed the SCQ to screen for autistic features and the Development and Well Being Assessment (DAWBA) psychiatric interview. A consensus diagnosis of ASD was assigned by two child psychiatrists following review of the DAWBA parental interview and corresponding DAWBA teacher questionnaire. SETTING: Community-based follow-up. RESULTS: Using the established SCQ cut-off (scores >=15), 28 (16%) extremely preterm children screened positive for ASD. Eleven (6%) were assigned a diagnosis of ASD. Using this cut-off, the SCQ had 82% sensitivity and 88% specificity for identifying ASD in this population. Using a receiver operating characteristic curve, SCQ scores >=14 had optimal diagnostic utility (area under curve: 0.94; sensitivity: 91%; specificity: 86%). Positive predictive value was relatively low (31%) resulting in numerous over-referrals. However, children with false positive screens had significantly worse neuro-developmental, cognitive and behavioural outcomes than those with true negative screens. CONCLUSION: The SCQ has good diagnostic utility for identifying ASD in extremely preterm children and is a useful screening tool in this population. Children with false positive screens represent a high-risk group in whom further diagnostic assessment would be beneficial. PMID- 21030373 TI - Paediatric sickle cell disease: pulmonary hypertension but normal vascular resistance. AB - BACKGROUND: Adults with sickle cell disease (SCD) and pulmonary hypertension have high mortality but death in SCD children with pulmonary hypertension is rare. The authors hypothesised that pulmonary hypertension in SCD children may be secondary to anaemia-induced high cardiac output rather than pulmonary vascular disease. METHODS: Two independent, validated techniques were used to estimate pulmonary vascular resistance (PVR) in 50 SCD children and 50 matched controls. Tricuspid regurgitant jet velocity (TRV) and right ventricular outflow tract velocity time integral were measured using Doppler echocardiography; PVR was calculated from their ratio. Acetylene rebreathing technique using respiratory mass spectrometry was also performed to calculate pulmonary blood flow and stroke index, an estimate of PVR. RESULTS: TRV was higher in SCD children compared with controls (2.28 vs 2.14 m/s, p=0.02). Fifteen of 34 (44%) children with haemoglobin of the SS genotype (HbSS) versus 1/16 (6%) children with haemoglobin of the SC genotype (HbSC) had pulmonary hypertension (TRV>=2.5 m/s) (p=0.009). Right ventricular stroke volume was higher (p<0.05) and Doppler PVR lower (1.20 (0.19) vs 1.31 (0.20) Wood units, p=0.04) in SCD children with pulmonary hypertension compared with controls. Qpeff and stroke index were higher in SCD children compared with controls (p<0.001 for both) and correlated with anaemia (p<0.001) and TRV (p=0.03). There was no correlation between TRV and history of asthma or acute chest syndrome. CONCLUSIONS: Pulmonary hypertension due to raised cardiac output is common in HbSS SCD children and is associated with normal PVR. PVR should be measured before therapy with agents such as sildenafil or bosentan is contemplated. PMID- 21030374 TI - Temporary brittle bone disease versus suspected non-accidental skeletal injury. PMID- 21030375 TI - NICE recommendations for the formal assessment of babies with prolonged jaundice: too much for well infants? PMID- 21030376 TI - Diagnosis of pityriasis versicolor in paediatrics: the evoked scale sign. PMID- 21030377 TI - Juvenile dermatomyositis with tongue calcinosis and poor growth. PMID- 21030378 TI - Influenza A infection in young infants. AB - OBJECTIVE: To determine the clinical characteristics of infants <=2 months old hospitalised with influenza A. STUDY DESIGN: The study was a retrospective analysis of infants <=2 months old hospitalised with fever, respiratory distress and/or sepsis. Clinical signs, laboratory values, hospital duration and outcome were compared between children with influenza A and other viruses. RESULTS: The charts of 268 infants were reviewed. 29 (11%) children had laboratory-confirmed influenza A infection. Unique features associated with influenza infection included the high number presenting with fever (97%) and a history of exposure to family members with a flu-like illness (69%). A significantly lower rate of respiratory distress was observed in the influenza group compared with respiratory syncytial virus (RSV) (24% vs 89%, p<=0.001). Median duration of hospitalisation for influenza was shorter than RSV (4 days vs 6 days, p<0.001). CONCLUSIONS: In young infants, influenza A is a relatively mild disease compared to RSV and is primarily associated with upper respiratory tract manifestations. PMID- 21030379 TI - Severe iron deficiency anaemia and ischaemic stroke in children. AB - Iron deficiency anaemia (IDA) has a peak prevalence of 4-8% in children aged 1-3 years of age and is known to be associated with developmental delay, lethargy, irritability and cognitive problems. Rarely, IDA has also been reported as a risk factor for stroke in otherwise healthy children. We report a series of four young children aged 14 months to 48 months with significant IDA. Three children had venous sinus thrombosis and one had arterial ischaemic stroke, without other risk factors. We discuss the potential underlying mechanisms and review the relevant literature. This report further consolidates the evidence for a strong association between IDA and childhood stroke and highlights an easily treatable (and preventable) risk factor. PMID- 21030380 TI - Who should be offered sperm banking for fertility preservation? A survey of UK oncologists and haematologists. AB - BACKGROUND: Fertility after cancer therapy is a significant quality-of-life concern for many patients, their partners and families. Authoritative guidance states that men whose fertility may be affected by impending therapies should be offered sperm banking. Yet some patients are not offered this opportunity and are thereby disadvantaged. We sought to understand oncologists' and haematologists' decision making concerning sperm-banking referrals. DESIGN: We surveyed all oncologists and haematologists on the Royal College of Radiotherapists' Faculty of Oncology and British Society for Haematology circulation lists. RESULTS: From 2357 across all specialties, 499 responses were received: 253 haematologists and 246 oncologists (21% response rate). Twenty-one percent of respondents were unaware of local policies on sperm banking and 42% considered that sperm banking should be offered to more patients. Respondents' decisions reveal either assumptions about patients' needs based on characteristics such as age, sexual orientation and severity of illness or the influence of their own moral conclusions upon their patients. The survey identified paucity of training for clinicians, information for patients and systematic recording of discussions about fertility. CONCLUSIONS: A robust care infrastructure supporting male fertility storage is needed urgently to include targeted information for cancer clinicians and patients, identified individuals responsible for coordination and documentation of discussions with patients. PMID- 21030381 TI - The influence of tumor- and treatment-related factors on the development of local recurrence in osteosarcoma after adequate surgery. An analysis of 1355 patients treated on neoadjuvant Cooperative Osteosarcoma Study Group protocols. AB - BACKGROUND: Local recurrence (LR) in osteosarcoma is associated with very poor prognosis. We sought to evaluate which factors correlate with LR in patients who achieved complete surgical remission with adequate margins. PATIENTS AND METHODS: We analyzed 1355 patients with previously untreated high-grade central osteosarcoma of the extremities, the shoulder and the pelvis registered in neoadjuvant Cooperative Osteosarcoma Study Group trials between 1986 and 2005. Seventy-six patients developed LR. RESULTS: Median follow-up was 5.56 years. No participation in a study, pelvic tumor site, limb-sparing surgery, soft tissue infiltration beyond the periosteum, poor response to neoadjuvant chemotherapy, failure to complete the planned chemotherapy protocol and biopsy at a center other than the one performing the tumor resection were significantly associated with a higher LR rate. No differences were found for varying surgical margin widths. Surgical treatment at centers with small patient volume and additional surgery in the primary tumor area, other than biopsy and tumor resection, were significantly associated with a higher rate of ablative surgery. CONCLUSIONS: Patient enrollment in clinical trials and performing the biopsy at experienced institutions capable of undertaking the tumor resection without compromising the oncological and functional outcome should be pursued in the future. PMID- 21030382 TI - The predictive and prognostic value of circulating endothelial cells in advanced colorectal cancer patients receiving first-line chemotherapy and bevacizumab. PMID- 21030383 TI - Suboptimal survival of male germ-cell tumors in southern Portugal--a population based retrospective study for cases diagnosed in 1999 and 2000. AB - BACKGROUND: The outcome of germ-cell tumors (GCTs) is a hallmark of good-quality cancer care. In the Eurocare-4 study, the mean 5-year survival for patients diagnosed from 1995 to 1999 was 95.5%. PATIENTS AND METHODS: We carried out a population-based retrospective chart review study of male patients diagnosed with GCT in 1999 and 2000 in southern Portugal (2 119 065 males). RESULTS: There were 87 GCTs-79 testicular, 2 retroperitoneal, 3 mediastinal, 2 of the central nervous system and 1 of the stomach. For the 81 patients with testicular or retroperitoneal primaries, 35 had stage I, 13 stage II and 30 stage III at presentation (3 unknown). Classification by International Germ Cell Consensus Classification Group criteria, 17 belonged to the poor prognosis group (mediastinal primary 3, liver metastases 11 and very elevated markers 3). With median follow-up of 89 months, the 5-year absolute overall survival was 80% (100% for stage I, 92% for stage II and 53% for stage III disease). CONCLUSIONS: While GCT incidence was similar to neighboring Spain, the 5-year overall survival was lower than that of other European countries. This may result from delays in diagnosis, suggested by high proportion of high-stage and large-burden disease, and poor adherence to recommended treatment algorithms. PMID- 21030384 TI - Functional mixture regression. AB - In functional linear models (FLMs), the relationship between the scalar response and the functional predictor process is often assumed to be identical for all subjects. Motivated by both practical and methodological considerations, we relax this assumption and propose a new class of functional regression models that allow the regression structure to vary for different groups of subjects. By projecting the predictor process onto its eigenspace, the new functional regression model is simplified to a framework that is similar to classical mixture regression models. This leads to the proposed approach named as functional mixture regression (FMR). The estimation of FMR can be readily carried out using existing software implemented for functional principal component analysis and mixture regression. The practical necessity and performance of FMR are illustrated through applications to a longevity analysis of female medflies and a human growth study. Theoretical investigations concerning the consistent estimation and prediction properties of FMR along with simulation experiments illustrating its empirical properties are presented in the supplementary material available at Biostatistics online. Corresponding results demonstrate that the proposed approach could potentially achieve substantial gains over traditional FLMs. PMID- 21030385 TI - Raising yield potential of wheat. II. Increasing photosynthetic capacity and efficiency. AB - Past increases in yield potential of wheat have largely resulted from improvements in harvest index rather than increased biomass. Further large increases in harvest index are unlikely, but an opportunity exists for increasing productive biomass and harvestable grain. Photosynthetic capacity and efficiency are bottlenecks to raising productivity and there is strong evidence that increasing photosynthesis will increase crop yields provided that other constraints do not become limiting. Even small increases in the rate of net photosynthesis can translate into large increases in biomass and hence yield, since carbon assimilation is integrated over the entire growing season and crop canopy. This review discusses the strategies to increase photosynthesis that are being proposed by the wheat yield consortium in order to increase wheat yields. These include: selection for photosynthetic capacity and efficiency, increasing ear photosynthesis, optimizing canopy photosynthesis, introducing chloroplast CO(2) pumps, increasing RuBP regeneration, improving the thermal stability of Rubisco activase, and replacing wheat Rubisco with that from other species with different kinetic properties. PMID- 21030386 TI - Dorsoventral variations in dark chilling effects on photosynthesis and stomatal function in Paspalum dilatatum leaves. AB - The effects of dark chilling on the leaf-side-specific regulation of photosynthesis were characterized in the C(4) grass Paspalum dilatatum. CO(2)- and light-response curves for photosynthesis and associated parameters were measured on whole leaves and on each leaf side independently under adaxial and abaxial illumination before and after plants were exposed to dark chilling for one or two consecutive nights. The stomata closed on the adaxial sides of the leaves under abaxial illumination and no CO(2) uptake could be detected on this surface. However, high rates of whole leaf photosynthesis were still observed because CO(2) assimilation rates were increased on the abaxial sides of the leaves under abaxial illumination. Under adaxial illumination both leaf surfaces contributed to the inhibition of whole leaf photosynthesis observed after one night of chilling. After two nights of chilling photosynthesis remained inhibited on the abaxial side of the leaf but the adaxial side had recovered, an effect related to increased maximal ribulose-1,5-bisphosphate carboxylation rates (V(cmax)) and enhanced maximal electron transport rates (J(max)). Under abaxial illumination, whole leaf photosynthesis was decreased only after the second night of chilling. The chilling-dependent inhibition of photosynthesis was located largely on the abaxial side of the leaf and was related to decreased V(cmax) and J(max), but not to the maximal phosphoenolpyruvate carboxylase carboxylation rate (V(pmax)). Each side of the leaf therefore exhibits a unique sensitivity to stress and recovery. Side-specific responses to stress are related to differences in the control of enzyme and photosynthetic electron transport activities. PMID- 21030387 TI - The N-glycan processing enzymes alpha-mannosidase and beta-D-N acetylhexosaminidase are involved in ripening-associated softening in the non climacteric fruits of capsicum. AB - Excessive softening of fruits during the ripening process leads to deterioration. This is of significant global importance as softening-mediated deterioration leads to huge postharvest losses. N-glycan processing enzymes are reported to play an important role during climacteric fruit softening: however, to date these enzymes have not been characterized in non-climacteric fruit. Two ripening specific N-glycan processing enzymes, alpha-mannosidase (alpha-Man) and beta-D-N acetylhexosaminidase (beta-Hex), have been identified and targeted to enhance the shelf life in non-climacteric fruits such as capsicum (Capsicum annuum). The purification, cloning, and functional characterization of alpha-Man and beta-Hex from capsicum, which belong to glycosyl hydrolase (GH) families 38 and 20, respectively, are described here. alpha-Man and beta-Hex are cell wall glycoproteins that are able to cleave terminal alpha-mannose and beta-D-N acetylglucosamine residues of N-glycans, respectively. alpha-Man and beta-Hex transcripts as well as enzyme activity increase with the ripening and/or softening of capsicum. The function of alpha-Man and beta-Hex in capsicum softening is investigated through RNA interference (RNAi) in fruits. alpha-Man and beta-Hex RNAi fruits were approximately two times firmer compared with the control and fruit deterioration was delayed by approximately 7 d. It is shown that silencing of alpha-Man and beta-Hex enhances fruit shelf life due to the reduced degradation of N-glycoproteins which resulted in delayed softening. Altogether, the results provide evidence for the involvement of N-glycan processing in non-climacteric fruit softening. In conclusion, genetic engineering of N-glycan processing can be a common strategy in both climacteric and non climacteric species to reduce the post-harvest crop losses. PMID- 21030388 TI - HAHB10, a sunflower HD-Zip II transcription factor, participates in the induction of flowering and in the control of phytohormone-mediated responses to biotic stress. AB - The transcription factor HAHB10 belongs to the sunflower (Helianthus annuus) HD Zip II subfamily and it has been previously associated with the induction of flowering. In this study it is shown that HAHB10 is expressed in sunflower leaves throughout the vegetative stage and in stamens during the reproductive stage. In short-day inductive conditions the expression of this gene is induced in shoot apexes together with the expression of the flowering genes HAFT and HAAP1. Transgenic Arabidopsis plants expressing HAHB10 cDNA under regulation either by its own promoter or by cauliflower mosaic virus (CaMV) 35S exhibited an early flowering phenotype. This phenotype was completely reverted in a non-inductive light regime, indicating a photoperiod-dependent action for this transcription factor. Gene expression profiling of Arabidopsis plants constitutively expressing HAHB10 indicated that specific flowering transition genes such as FT, FUL, and SEP3 were induced several fold, whereas genes related to biotic stress responses, such as PR1, PR2, ICS1, AOC1, EDS5, and PDF1-2a, were repressed. The expression of HAHB10 and of the flowering genes HASEP3 and HAFT was up-regulated by both salicylic acid (SA) treatment and infection with a virulent strain of Pseudomonas syringae. Basal SA and jasmonic acid (JA) levels in Arabidopsis plants ectopically expressing HAHB10 were similar to those of control plants; however, SA levels differentially increased in the transgenic plants after wounding and infection with P. syringae while JA levels differentially decreased. Taken together, the results indicated that HAHB10 participates in two different processes in plants: the transition from the vegetative to the flowering stage via the induction of specific flowering transition genes and the accumulation of phytohormones upon biotic stresses. PMID- 21030389 TI - Characterization of a common wheat (Triticum aestivum L.) TaSnRK2.7 gene involved in abiotic stress responses. AB - Sucrose non-fermenting-1-related protein kinase 2 (SnRK2) plays a key role in the plant stress signalling transduction pathway via phosphorylation. Here, a SnRK2 member of common wheat, TaSnRK2.7, was cloned and characterized. Southern blot analysis suggested that the common wheat genome contains three copies of TaSnRK2.7. Subcellular localization showed the presence of TaSnRK2.7 in the cell membrane, cytoplasm, and nucleus. Expression patterns revealed that TaSnRK2.7 is expressed strongly in roots, and responds to polyethylene glycol, NaCl, and cold stress, but not to abscisic acid (ABA) application, suggesting that TaSnRK2.7 might participate in non-ABA-dependent signal transduction pathways. TaSnRK2.7 was transferred to Arabidopsis under the control of the CaMV-35S promoter. Function analysis showed that TaSnRK2.7 is involved in carbohydrate metabolism, decreasing osmotic potential, enhancing photosystem II activity, and promoting root growth. Its overexpression results in enhanced tolerance to multi-abiotic stress. Therefore, TaSnRK2.7 is a multifunctional regulatory factor in plants, and has the potential to be utilized in transgenic breeding to improve abiotic stress tolerance in crop plants. PMID- 21030390 TI - Contrast in chloride exclusion between two grapevine genotypes and its variation in their hybrid progeny. AB - Potted grapevines of 140 Ruggeri (Vitis berlandieri * Vitis rupestris), a good Cl(-) excluder, and K 51-40 (Vitis champinii * Vitis riparia 'Gloire'), a poor Cl(-) excluder, and of a family obtained by crossing the two genotypes, were used to examine the inheritance of Cl(-) exclusion. Rooted leaves were then used to further investigate the mechanism for Cl(-) exclusion in 140 Ruggeri. In both a potting mix trial (plants watered with 50 mM Cl(-)) and a solution culture trial (plants grown in 25 mM Cl(-)), the variation in Cl(-) accumulation was continuous, indicating multiple rather than single gene control for Cl(-) exclusion between hybrids within the family. Upper limits of 42% and 35% of the phenotypic variation in Cl(-) concentration could be attributed to heritable sources in the potting mix and solution culture trials, respectively. Chloride transport in roots of rooted leaves of both genotypes appeared to be via the symplastic pathway, since addition of 8-hydroxy-1,3,6-pyrenetrisulphonic acid (PTS), an apoplastic tracer, revealed no obvious PTS fluorescence in the laminae of either genotype, despite significant accumulation of Cl(-) in laminae of K 51 40 during the PTS uptake period. There was no significant difference in either unidirectional (36)Cl(-) flux (10 min) or (36)Cl(-) uptake (3 h) into roots of rooted leaves exposed to 5, 10, or 25 mM Cl(-). However, the percentage of (36)Cl(-) transported to the lamina (3 h) was significantly lower in 140 Ruggeri than in K 51-40, supporting reduced Cl(-) loading into xylem and implicating the root stele in the Cl(-) exclusion mechanism. PMID- 21030391 TI - Anaesthetic management of patients with severe sepsis. AB - Severe sepsis, a syndrome characterized by systemic inflammation and acute organ dysfunction in response to infection, is a major healthcare problem affecting all age groups throughout the world. Anaesthetists play a central role in the multidisciplinary management of patients with severe sepsis from their initial deterioration at ward level, transfer to the diagnostic imaging suite, and intraoperative management for emergency surgery. The timely administration of appropriate i.v. antimicrobial therapy is a crucial step in the care of patients with severe sepsis who may require surgery to control the source of sepsis. Preoperative resuscitation, aimed at optimizing major organ perfusion, is based on judicious use of fluids, vasopressors, and inotropes. Intraoperative anaesthesia management requires careful induction and maintenance of anaesthesia, optimizing intravascular volume status, avoidance of lung injury during mechanical ventilation, and ongoing monitoring of arterial blood gases, lactate concentration, haematological and renal indices, and electrolyte levels. Postoperative care overlaps with ongoing management of the severe sepsis syndrome patient in the intensive care unit. These patients are by definition, high risk, already requiring multiple supports, and require experienced and skilful decision making to optimize their chances of a favourable outcome. Similar to acute myocardial infarction, stroke, or acute trauma, the initial hours (golden hours) of clinical management of severe sepsis represent an important opportunity to reduce morbidity and mortality. Rapid clinical assessment, resuscitation and surgical management by a focused multidisciplinary team, and early effective antimicrobial therapy are the key components to improved patient outcome. PMID- 21030392 TI - Blunt trauma of the anterior tibial artery in professional footballers. AB - Three cases of blunt trauma to the anterior tibial artery in professional footballers are described. Each case was managed conservatively, allowing the players to promptly return to competitive fixtures. We hope the outcomes of the cases described might be helpful for teams facing the challenge of managing similar injuries. PMID- 21030393 TI - Atrial flutter ablation through the azygous continuation in a patient with inferior vena cava interruption. AB - Ablation of atrial flutter (AFL) requires linear radiofrequency application; these procedures are usually performed via a femoral approach from the inferior vena cava (IVC). Congenital anomalies of this venous system may limit catheter ablation. This report presents ablation of an AFL through the azygous continuation and also reviews the prevalence of congenital IVC interruption among patients referred for AFL ablation. PMID- 21030394 TI - Fixing flaws in Medicare drug coverage that prompt insurers to avoid low-income patients. AB - Since 2006 numerous insurers have stopped serving the low-income segment of the Medicare Part D program, forcing millions of beneficiaries to change prescription drug plans. Using data from participating plans, we found that Medicare payments do not sufficiently reimburse insurers for the relatively high medication use among this population, creating perverse incentives for plans to avoid this part of the Part D market. Plans can accomplish this by increasing their premiums for all beneficiaries to an amount above regional benchmarks. We demonstrate that improving the accuracy of Medicare's risk and subsidy adjustments could mitigate these perverse incentives. PMID- 21030395 TI - Protective effect of BCG vaccination in a nursery outbreak in 2009: time to reconsider the vaccination threshold? AB - BACKGROUND: In July 2008 a case of smear-positive pulmonary tuberculosis (TB) in a white UK-born nursery teacher was notified in London. The case had been symptomatic for 9 months while working in the nursery. The outbreak is described and the protective effect of BCG vaccination against latent Mycobacterium tuberculosis infection as measured by an interferon gamma release assay (IGRA) is assessed. METHODS: Screening by chest X-ray and IGRA of nursery children, staff and their contacts was conducted using a 'stone-in-the pond' approach. Information was collected on various factors including BCG vaccination status, and data were analysed using multivariable logistic regression. RESULTS: Overall, 168 children, 31 staff members and 57 other adults associated with the nursery were screened for TB. There were 12 cases of active TB and 43 cases of latent TB (72% children). 37.5% (95% CI 18% to 56%) and 40% (95% CI 30% to 50%) had a positive IGRA among teachers and children, respectively. 42% of children and 60% of adults were BCG vaccinated. In the adjusted analysis, BCG vaccination showed a significant protective effect against M tuberculosis infection in children (OR 0.25, 95% CI 0.09 to 0.69) and being taught by the index case was associated with acquiring TB infection (OR 18.91, 95% CI 4.43 to 80.79). A vaccine effectiveness of 66% was calculated, implying that 21 of the 32 infections could have been avoided if all children had been vaccinated with BCG. CONCLUSIONS: This outbreak shows extensive transmission of TB among very young children. BCG seems to have a protective effect against TB infection as assessed by positive IGRA in this cohort. PMID- 21030397 TI - Examples of Mesh and NURBS modelling for in vivo lung counting studies. AB - Realistic calibration coefficients for in vivo counting installations are assessed using voxel phantoms and Monte Carlo calculations. However, voxel phantoms construction is time consuming and their flexibility extremely limited. This paper involves Mesh and non-uniform rational B-splines graphical formats, of greater flexibility, to optimise the calibration of in vivo counting installations. Two studies validating the use of such phantoms and involving geometry deformation and modelling were carried out to study the morphologic effect on lung counting efficiency. The created 3D models fitted with the reference ones, with volumetric differences of <5 %. Moreover, it was found that counting efficiency varies with the inverse of lungs' volume and that the latter primes when compared with chest wall thickness. Finally, a series of different thoracic female phantoms of various cup sizes, chest girths and internal organs' volumes were created starting from the International Commission on Radiological Protection (ICRP) adult female reference computational phantom to give correction factors for the lung monitoring of female workers. PMID- 21030396 TI - New insights in cough. AB - Chronic cough is common, blights patients' lives and is hard to treat. Chronic cough patients demonstrate high objective cough rates and as a group have increased cough reflex sensitivity. However, conventional cough challenge techniques show substantial overlap with normal subjects. This suggests that other important mechanisms have yet to be determined. For the last two decades, chronic cough has been considered to be caused by gastro-oesophageal reflux, post nasal drip or asthma. However, many patients with these conditions do not have cough, and in those with cough, the response to specific treatments is unpredictable at best. In addition, many chronic cough patients do not have an identifiable cause. This raises questions about the concept of a triad of treatable causes for chronic cough. Our current understanding of the neurophysiology of the cough reflex is largely derived from animal work with limited data in humans. By analogy with chronic pain syndromes, both peripheral and central sensitization may be important mechanisms in chronic cough, and are under active investigation. We need to understand the mechanisms underlying sensitization, how they interact with cough triggers and their relationship with the sensations that drive the urge to cough, and the subsequent motor cough response in chronic cough. Only then will we develop effective interventions. PMID- 21030398 TI - Individual monitoring in nuclear medicine therapeutic procedures using extremity dosemeters LiF(Mg, Cu, P). AB - Unsealed beta-gamma-emitting sources are used (15 GBq (90)Y each session) in nuclear medicine therapeutic procedures. Inside the manipulation cell and while giving the injection to the patient, the skin exposure is very high; electron radiation field is not homogeneous and thus the exposure of the extremities is not uniform. Particular individual monitoring is adopted: single thermoluminescence dosemeter, wrapped in polyethylene film and placed on an adhesive tape, is positioned on the tip of the fingers; 6-10 dosemeters are assigned to each operator per session. The energy and angle response is studied for X-ray spectra, (90)Sr/Y and (204)Tl--a unique mean calibration factor is calculated in order to estimate H(p)(0.07). Performance of dosemeter is analysed according to ISO 62387-1(2007) and the combined uncertainty (calculated using the Monte Carlo method) results lie in the order of 11 %. This method reveals the critical step of manipulation and administration and ensures that dose limits are not exceeded. PMID- 21030399 TI - Directional distribution of the ambient neutron dose equivalent from 145-MeV 19F projectiles incident on thick Al target. AB - The directional distribution of the ambient neutron dose equivalent from 145-MeV (19)F projectiles bombarding a thick aluminium target is measured and analysed. The measurements are carried out with a commercially available dose equivalent meter at 0 degrees , 30 degrees , 60 degrees and 90 degrees with respect to the beam direction. The experimental results are compared with calculated doses from EMPIRE nuclear reaction code and different empirical formulations proposed by others. The results are also compared with the measured data obtained from an earlier experiment at a lower projectile energy of 110 MeV for the same target projectile combination. PMID- 21030400 TI - Comparison of various anthropomorphic phantom types for in vivo measurements by means of Monte Carlo simulations. AB - Three widely used anthropomorphic phantoms are analysed with regard to their suitability for the efficiency calibration of whole-body counters (WBCs): a Bottle Manikin Absorber (BOMAB) phantom consisting of water-filled plastic containers, a St Petersburg block phantom (Research Institute of Sea Transport Hygiene, St Petersburg) made of polyethylene bricks and a mathematical Medical Internal Radiation Dose (MIRD) phantom, each of them representing a person weighing 70 kg. The analysis was performed by means of Monte Carlo simulations with the Monte Carlo N-Particle transport code using detailed mathematical models of the phantoms and the WBC at Forschungszentrum Julich (FZJ). The simulated peak efficiencies for the BOMAB phantom and the MIRD phantom agree very well, but the results for the St Petersburg phantom are considerably higher. Therefore, WBCs similar to that at FZJ will probably underestimate the activity of incorporated radionuclides if they are calibrated by means of a St Petersburg phantom. Finally, the results from this work are compared with the conclusions from other studies dealing with block and BOMAB phantoms. PMID- 21030401 TI - Pneumothorax after bevacizumab-containing chemotherapy: a case report. AB - Bevacizumab added to 5-fluorouracil-based chemotherapy can improve outcomes in patients with metastatic colorectal cancer. Bevacizumab had several notable adverse effects including bowel perforation but pneumothorax had never been reported in the available English literature. We reported a 45-year-old male with lung metastases from colorectal cancer who had spontaneous pneumothorax after the second cycle of bevacizumab-containing chemotherapy. His pneumothorax resolved after tube thoracostomy with a small caliber catheter. The mechanism of pneumothorax developed after bevacizumab therapy was not clear as bowel perforation but tumor necrosis with ruptured parietal pleura might be the cause. In patients who had chest discomfort after bevacizumab-containing therapy, pneumothorax should never be overlooked as one of the differential diagnoses. PMID- 21030402 TI - Are socio-economic groupings the most appropriate method for judging health equity between countries? PMID- 21030403 TI - Nitric oxide enhances salt secretion and Na(+) sequestration in a mangrove plant, Avicennia marina, through increasing the expression of H(+)-ATPase and Na(+)/H(+) antiporter under high salinity. AB - Modulation of nitric oxide (NO) on ion homeostasis, by enhancing salt secretion in the salt glands and Na(+) sequestration into the vacuoles, was investigated in a salt-secreting mangrove tree, Avicennia marina (Forsk.) Vierh. The major results are as follows: (i) under 400 mM NaCl treatment, the application of 100 uM sodium nitroprusside (SNP), an NO donor, significantly increased the density of salt crystals and salt secretion rate of the leaves, along with maintaining a low Na(+) to K(+) ratio in the leaves. (ii) The measurement of element contents by X-ray microanalysis in the epidermis and transversal sections of A. marina leaves revealed that SNP (100 uM) significantly increased the accumulation of Na(+) in the epidermis and hypodermal cells, particularly the Na(+) to K(+) ratio in the salt glands, but no such effects were observed in the mesophyll cells. (iii) Using non-invasive micro-test technology (NMT), both long-term SNP (100 uM) and transient SNP (30 uM) treatments significantly increased net Na(+) efflux in the salt glands. On the contrary, NO synthesis inhibitors and scavenger reversed the effects of NO on Na(+) flux. These results indicate that NO enhanced salt secretion by increasing net Na(+) efflux in the salt glands. (iv) Western blot analysis demonstrated that 100 uM SNP stimulated protein expressions of plasma membrane (PM) H(+)-ATPase and vacuolar membrane Na(+)/H(+) antiporter. (v) To further clarify the molecular mechanism of the effects of NO on enhancing salt secretion and Na(+) sequestration, partial cDNA fragments of PM H(+)-ATPase (HA1), PM Na(+)/H(+) antiporter (SOS1) and vacuolar Na(+)/H(+) antiporter (NHX1) were isolated and transcriptional expression of HA1, SOS1, NHX1 and vacuolar H(+) ATPase subunit c (VHA-c1) genes were analyzed using real-time quantitative polymerase chain reaction. The relative transcript abundance of the four genes were markedly increased in 100 uM SNP-treated A. marina. Moreover, the increase was reversed by NO synthesis inhibitors and scavenger. Taken together, our results strongly suggest that NO functions as a signal in salt resistance of A. marina by enhancing salt secretion and Na(+) sequestration, which depend on the increased expression of the H(+)-ATPase and Na(+)/H(+) antiporter. PMID- 21030404 TI - A semi-physiological model of cold hardening and dehardening in walnut stem. AB - It has been hypothesized that the increase in temperature in this century could lead to an increase in frost damage to plant tissues. Several models have been proposed to describe the development of cold hardiness, but never taking into account extreme climatic and/or physiological events. Our results on walnut tree (Juglans regia L.) show that cold hardiness was best correlated with average daily temperatures minimal temperatures over the last 15 days before sampling (T(min 15 days)), indicating that the freezing tolerance depended on the tree's climatic history. Moreover, this study also shows that the accumulation of sucrose and the water content (WC) decrease are an essential step towards cold hardiness. Thus, a simple linear model based on climatic (T(min 15 days)) and physiological (soluble sugars, WC) explanatory variables was developed to predict the cold hardiness level in walnut stem at any time during the leafless period. Each of the three input variables can be assigned a specific role contributing to the simulated function, cold hardiness. The extent and robustness of this relation was assessed on extreme physiological events on walnut trees bearing three main branches. On each tree, one branch was defoliated to limit the local carbohydrate and transpiration, one was girdled to increase local carbohydrate and prevent carbohydrate export and the third one was kept untreated as control. As expected, these treatments impacted both local carbon reserves and WC in the stems born by each main branch in comparison with the control on the same tree. The impact of these treatments on stem's freezing tolerance, as evaluated by an electrolyte leakage method (LT50), confirmed the direct impact of soluble sugar and WC on cold hardiness over a wide range of carbohydrate and WC. This is discussed in relation to the branch autonomy theory for carbon but also for water during summer growth and winter periods. The present study demonstrates the importance of physiological parameters in the prediction of cold hardiness and proposes a way to model cold hardiness with extreme climatic and/or physiological events. PMID- 21030405 TI - Clonal reproduction and natural variation of Populus canescens patches. AB - Trees growing in their natural habitat represent a valuable resource for elucidating mechanisms of adaptation to environmental constraints. Along the Erqis river, there are various Populus forests, which provide 'natural laboratories' for studying tree ecophysiological responses to their habitat. Reproduction strategies and natural variation of the 'mosaic' distributed Populus canescens patches were studied using a proteomic approach and nuclear microsatellite markers. Clonal reproduction was the primary reproduction strategy of these P. canescens patches. Forty-eight percent of the locations represented in one or two P. canescens patches were identified. In total, 83 different proteins were identified in 118 of 119 protein spots, most of them involved in metabolism. Distinct proteomes and post-translational modifications were found in different P. canescens patches. The differences in the proteomes originate both from the expression of different protein isoforms with the same function and from the differential expression of proteins with different functions, suggesting that different patches might have a functional basis for their adaptation to their environments. Our studies provide a good example of applying proteomics to measure natural variation between patches and will provide a basis for understanding how trees survive through their responses to natural conditions. PMID- 21030406 TI - Differential impact of chronic ozone exposure on expanding and fully expanded poplar leaves. AB - Populus tremula L. * Populus alba L. (Populus *c anescens (Aiton) Smith) - clone INRA 717-1-B4 saplings (50 cm apex to base and carrying 19 leaves on average) - were followed for 28 days. Half of the trees were grown in charcoal-filtered air while the other half were exposed to 120 ppb ozone for 11 h a day during the light period. The expanding leaf number 4 was tagged at the beginning of the experiment and finished expansion between 7 and 14 days. These leaves were harvested weekly for biochemical and proteome analyses using quantitative bidimensional electrophoresis (DiGE). Independent of the ozone treatment, all the analyses allowed a distinction between expanding and adult leaves. The results indicate that during the expansion phase (Days 0-7) the enzymatic machinery of the leaves is set up, and remains dynamically stable in the adult leaves (Days 14 28). Although ozone had no apparent effect on expanding leaves, the metabolic stability in fully expanded leaves observed in ozone-free plants was disturbed after 2 weeks of exposure and a stress-induced response became apparent. PMID- 21030407 TI - The effect of tree architecture on conduit diameter and frequency from small distal roots to branch tips in Betula pendula, Picea abies and Pinus sylvestris. AB - We studied the effect of tree architecture on xylem anatomy in three Betula pendula Roth., three Picea abies (L.) H. Karst. and three Pinus sylvestris (L.) trees (mean age 35 years). First, the analysis of conduit anatomy in different tree parts showed that conduits tapered and their frequency increased from roots (>= 2 mm) to stem, from stem to branches and further to leaf petioles in B. pendula. Conduit anatomy in lateral and main roots, as well as lateral and main branches, significantly differed from each other in all the studied species. The increase in conduit diameter and decrease in frequency from the pith to the bark were clear aboveground, but variable patterns were observed belowground. In the leaf petioles of B. pendula, conduit diameter increased and conduit frequency decreased with increasing individual leaf area. Second, the results concerning the scaling of conduit diameter were compared with the predictions of the general vascular scaling model (WBE model) and Murray's law. The scaling parameter values at the tree level corresponded with the predictions of the WBE model in all the studied trees except for one tree of both conifer species. However, the scaling parameter values changed from one tree compartment to another rather than remaining uniform inside a tree, as assumed by the WBE model. The assumptions of the WBE model of a constant conductivity ratio, constant tapering and an unchanged total number of conduits were not fulfilled. When the conductivity ratio and relative tapering were plotted together, the results aboveground corresponded quite well with Murray's law: the conductivity ratio increased when relative tapering decreased. Our results support the theory that trees adjust both their macro- and microstructure to maximize their water transport efficiency, but also to prevent embolism and ensure mechanical safety. PMID- 21030408 TI - Proteomic analysis of membrane preparations from developing Pinus radiata compression wood. AB - For coniferous gymnosperms, few data exist as to the contribution of the membrane associated proteome to cell wall and wood formation. In this study, we begin to address this knowledge deficiency by examining the proteomic profile of Golgi enriched membrane preparations derived from developing Pinus radiata compression wood. These membrane preparations were generated by a combination of discontinuous sucrose gradient centrifugation and Triton X-114-based phase separation. Fractionation by phase separation removed contaminating proteins associated with the cytoskeleton and enabled the discrimination between soluble and membrane-bound/integral proteins. The proteomic analysis of the resulting aqueous and detergent phases using high-performance liquid chromatography-tandem mass spectrometry resulted in the identification of 175 proteins. The majority of the identified proteins were membrane bound/integral and originated from cellular components such as the nucleus, plastids, endoplasmic reticulum, plasma membrane and Golgi vesicles. On the basis of bioinformatic analysis, many of the identified proteins were predicted to be involved either in the regulation of wood formation or in cell wall biosynthesis, which indicated that the proteomic analysis of non-cytosolic proteins in developing xylem is a useful strategy to investigate the molecular aspects of wood formation in pine. PMID- 21030409 TI - Chronic vagus nerve stimulation: a new and promising therapeutic approach for chronic heart failure. AB - AIMS: In chronic heart failure (CHF), reduced vagal activity correlates with increased mortality and acute decompensation. Experimentally, chronic vagus nerve stimulation (VNS) improved left ventricular (LV) function and survival; clinically, it is used for the treatment of drug-refractory epilepsy. We assessed safety and tolerability of chronic VNS in symptomatic CHF patients, using a novel implantable nerve stimulation system. The secondary goal was to obtain preliminary data on clinical efficacy. METHODS AND RESULTS: This multi-centre, open-label phase II, two-staged study (8-patient feasibility phase plus 24 patient safety and tolerability phase) enrolled 32 New York Heart Association (NYHA) class II-IV patients [age 56 +/- 11 years, LV ejection fraction (LVEF) 23 +/- 8%]. Right cervical VNS with CardioFit (BioControl Medical) implantable system started 2-4 weeks after implant, slowly raising intensity; patients were followed 3 and 6 months thereafter with optional 1-year follow-up. Overall, 26 serious adverse events (SAEs) occurred in 13 of 32 patients (40.6%), including three deaths and two clearly device-related AEs (post-operative pulmonary oedema, need of surgical revision). Expected non-serious device-related AEs (cough, dysphonia, and stimulation-related pain) occurred early but were reduced and disappeared after stimulation intensity adjustment. There were significant improvements (P < 0.001) in NYHA class quality of life, 6-minute walk test (from 411 +/- 76 to 471 +/- 111 m), LVEF (from 22 +/- 7 to 29 +/- 8%), and LV systolic volumes (P = 0.02). These improvements were maintained at 1 year. CONCLUSIONS: This open-label study shows that chronic VNS in CHF patients with severe systolic dysfunction may be safe and tolerable and may improve quality of life and LV function. A controlled clinical trial appears warranted. PMID- 21030410 TI - Aqueous humour penetration of moxifloxocin and gatifloxacin eye drops in different dosing regimens before phacoemulsification surgery. AB - AIM: To compare the aqueous humour penetration of moxifloxacin 0.5% and gatifloxacin 0.3% eye drops administered in two different dosing regimens during phacoemulsification surgery. METHODS: This prospective, randomised study included 97 patients. The patients were randomly divided into two treatment groups to receive either moxifloxacin or gatifloxacin. All patients received the topical antibiotics four times per day for 2 days prior to surgery. Patients in each group were further subdivided to receive additional doses of antibiotic drops as two drops 30 min apart (subgroup 1) versus four drops 10 min apart (subgroup 2) 1 h prior to the surgery. At the beginning of surgery, 0.1 ml of aqueous humour was aspirated, and the concentrations of moxifloxacin and gatifloxacin were analysed by high-performance liquid chromatography. RESULTS: The mean concentrations of moxifloxacin and gatifloxacin in the aqueous humour were 0.72 +/- 0.40 MUg/ml and 0.47 +/- 0.29 MUg/ml, respectively, in the first subgroup, and 1.95 +/- 1.05 MUg/ml and 0.77 +/- 0.52 MUg/ml, respectively, in the second subgroup. Both the inter-group (p=0.006 and p=0.000, respectively) and the intra-group (p=0.000 and p=0.035, respectively) differences between the aqueous humour concentrations of moxifloxacin and gatifloxacin subgroups were statistically significant. CONCLUSION: Moxifloxacin, given in the same dosage, penetrated the aqueous humour better then gatifloxacin during cataract surgery. The penetration of both antibiotics increased significantly when the dosage of the agent was doubled. PMID- 21030411 TI - Role of tumour necrosis factor-alpha (TNFalpha) in the functional properties of hyalocytes. AB - BACKGROUND/AIM: Tumour necrosis factor-alpha (TNFalpha) is an inflammatory cytokine that is upregulated in various vitreoretinal diseases including uveitis and diabetic retinopathy. Recently, our studies have indicated that hyalocytes contribute to the pathogenesis of these diseases. However, the impact of TNFalpha on the functional properties of hyalocytes is unknown. METHODS: Hyalocytes were isolated from bovine eyes. Cellular proliferation, migration and gel contraction in response to TNFalpha and the other inflammatory cytokines were analysed by thymidine uptake, Boyden's chamber assay and collagen gel contraction assay, respectively. Furthermore, we estimated the effect of dexamethasone on these properties of hyalocytes. RESULTS: TNFalpha promoted proliferation, migration and gel contraction by hyalocytes. Dexamethasone inhibited TNFalpha-induced proliferation but not migration. Dexamethasone did not inhibit TNFalpha-induced gel contraction but further increased contraction. Furthermore, dexamethasone inhibited TNFalpha-induced extracellular signal-related kinase (ERK)1/2 phosphorylation in hyalocytes. CONCLUSION: This study indicates that TNFalpha in vitreous and retina causes activation of hyalocytes, and the activated hyalocytes contribute to the pathogenesis of inflammatory vitreoretinal diseases. Steroid treatment appears to inhibit the activation of hyalocytes in the early stages of the diseases, but might have adverse effects in the late stage through membrane contraction. PMID- 21030412 TI - Amphotericin B and natamycin are not synergistic in vitro against Fusarium and Aspergillus spp. isolated from keratitis. PMID- 21030413 TI - Imaging of the retinal nerve fibre layer with spectral domain optical coherence tomography for glaucoma diagnosis. AB - Optical coherence tomography (OCT) techniques have been applied to develop a new generation of the technology, called spectral domain (SD) or Fourier domain (FD) OCT. The commercially available SD-OCT technology offers benefits over the conventional time domain (TD) OCT such as a scanning speed up to 200 times faster and higher axial resolution (3 to 6 MUm). Overall, SD-OCT offers improved performance in terms of reproducibility. SD-OCT has a level of discriminating capability, between healthy and perimetric glaucoma eyes similar to that obtained with TD-OCT. Furthermore, the capabilities and features of SD-OCT are rapidly evolving, mainly due to three-dimensional imaging and image rendering. More sophisticated approaches for macular and optic disc assessment are expected to be employed in clinical practice. Analysis software should be further refined for interpretation of SD-OCT images in order to enhance the sensitivity and specificity of glaucoma diagnostics. Most importantly for SD-OCT is determination of its ability to diagnostic structural glaucomatous progression. Considering the recent launch time of the commercially available SD-OCT and slow progressing characteristic of glaucoma, we must wait for longitudinal SD-OCT data, with a long enough follow-up, to become available. PMID- 21030414 TI - Strabismus: aligning the doctor's vision with the patient's need. PMID- 21030415 TI - Correlation between high-resolution optical coherence tomography (OCT) images and histopathology in an iodoacetic acid-induced model of retinal degeneration in rabbits. AB - BACKGROUND: Recent research on macular disease has prompted investigation into the condition of the intersection of the inner and outer segments (IS/OS) and its relationship with retinal photoreceptor abnormalities. Because the relationship between optical coherence tomography (OCT) images and histopathology is unclear, we compared these in an iodoacetic acid (IAA)-induced model of photoreceptor degeneration in rabbits. METHODS: IAA (20 mg/kg), which is toxic to photoreceptors, was injected into six coloured rabbits. After IAA administration, nine retinas were used for histopathological study: three from rabbits surviving for 1 day and six from rabbits surviving for 4 months. Four healthy rabbit retinas served as controls. OCT images were taken before euthanasia. RESULTS: In the controls, OCT images revealed the IS/OS as a clear, straight line. In rabbits surviving for 1 day, the structure of the photoreceptor IS/OS was destroyed and the IS/OS boundary was not visible. In rabbits surviving for 4 months, the IS was still preserved, but the structure of the OS was destroyed or partially disorganised, and the IS/OS was observed as a wavy, broken line on the OCT images. CONCLUSION: The IS/OS on the OCT images reflected the histopathology of the inner and outer segments in a photoreceptor degeneration model. PMID- 21030416 TI - Association of tear proteins with Meibomian gland disease and dry eye symptoms. AB - AIM: Tear proteins have an important role in the maintenance of the ocular surface and modulation of biological processes, including inflammation, in dry eye. Meibomian gland disease (MGD) is a condition that can increase inflammation in the ocular surface, but tear protein changes due to MGD have not been documented. This study evaluated the possible association of tear proteins with severity of MGD in dry eye. METHODS: Twenty-four patients with dry eye were evaluated. The panel of proteins found previously to be of interest and evaluated in this study were alpha-enolase, alpha-1-acid glycoprotein 1, S100A8 (calgranulin A), S100A9 (calgranulin B), S100A4 and S100A11 (calgizzarin), prolactin-inducible protein (PIP), lipocalin-1, lactoferrin and lysozyme. Tear protein ratios for each of 24 patients were calculated relative to pooled control from 18 healthy people, using isobaric tagging for relative and absolute quantification (iTRAQ)-based proteomics combined with two-dimensional-nanoliquid chromatography (LC)-nano-electrospray ionisation (ESI)-mass spectrometry (MS)/MS. The severity of MGD was clinically classified into grades 0-3 based on biomicroscopic signs. RESULTS: The levels of S100A8 and S100A9 were correlated to MGD severity. The level of S100A8 protein was significantly correlated to grittiness, whereas S100A8 and S100A9 were correlated to symptoms of redness and transient blurring. Lipocalin-1 was associated with heaviness of the eyelids and tearing. CONCLUSIONS: Distinct tear proteins are associated with MGD in dry eye patients, and some proteins were associated with distinct dry eye symptoms. These findings suggest that MGD may independently contribute to the symptomatology of dry eye patients. PMID- 21030417 TI - Ultrastructural and histochemical evaluation of appositional mineralization of circumpulpal dentin at the crown- and root-analog portions of rat incisors. AB - Mineralization of circumpulpal dentin has been interpreted in such a way that predentin matrix is abruptly converted to almost fully mineralized dentin at the mineralization front. A group of investigators pointed out the existence of intermediary layer along the mineralization front of rat incisor dentin and claimed that dentin mineralization is a rather transient process. Owing to a paucity of information, however, the entity of transient mineralization of dentin has remained elusive. Here we confirmed the existence of a lightly mineralized layer (LL) along the mineralization front of rat incisor dentin, recognizable by both light and electron microscopy, in routinely processed specimens. LL less than 3 um thick was shown to be located along the mineralization front of crown analog dentin and tapered out toward the root analog of the incisor. Electron microscopy revealed that mineral deposition first occurred in the non-collagenous matrix of LL and that mineralization of collagen fibers took place sometime later at the conventional mineralization front. Microscopic appearance of the mineral phase of LL varied considerably depending on the histological processing of ultrathin sections, thus explaining the inconsistent interpretation of dentin mineralization in previous studies. These data suggest that mineralization of circumpulpal dentin in rat incisors proceeds in a stepwise or a transient manner, initiated by crystal deposition in the non-collagenous matrix followed by massive mineral deposition in collagen fibers at the mineralization front. The thickness of LL where only the non-collagenous matrix is mineralized may vary in relation to differences in the local non-collagenous matrix and also the rate of collagen mineralization in the respective portions of circumpulpal dentin. PMID- 21030418 TI - Integrating clinical and basic research at the new Sheffield Institute for Translational Neuroscience. PMID- 21030419 TI - Academia-industry alliance: Belfer Institute and sanofi-aventis collaborate to develop new cancer therapeutics. PMID- 21030420 TI - 'Champalimaud Centre for the Unknown' opens in Lisbon. PMID- 21030423 TI - Stabilization process within a sewage sludge landfill determined through both particle size distribution and content of humic substances as well as by FT-IR analysis. AB - Landfill is largely considered as a reliable option for sewage sludge disposal in most metropolitan areas worldwide due to the huge quantities of this waste to be disposed of and the relatively low costs of such a kind of sludge management. It has been found that the sludge in the landfill degrades rapidly and becomes stabilized within a few years. In the present study, the sludge from different landfill stages was characterized by particle size distribution, humic substances contents and elemental composition, and Fourier transform infrared spectroscopy (FT-IR), as the landfill time increased. In general, the mean particle size of the sludge increased from 37 MUm at day 0 to 143 MUm at 300 days and the corresponding median particle size increased from 13 to 70 MUm. The stability of particle size distribution can be assessed by the mean or median particle size. The humic acid (HA) and fulvic acid (FA) contents extracted from dry sludge after different landfill periods increased from 4.2 and 2.7% of day 0 to 5.6 and 3.1%, respectively, at 400 days, thereby indicating that the stabilization process of sludge in a landfill is also a humification process. The HA samples contained more carbon and nitrogen, and less hydrogen and oxygen than the FA samples, indicating a high degree of maturity and humification of these HA samples. The FT IR spectra indicated that easily degradable organic matter components, such as aliphatic chains and protein, were distinctly decomposed during landfill. Based on the changes in the band relative intensity, it was concluded that after 300 days in a landfill the sludge is still in the process of degradation and maturity. PMID- 21030422 TI - Diagnosing and responding to violations in the positivity assumption. AB - The assumption of positivity or experimental treatment assignment requires that observed treatment levels vary within confounder strata. This article discusses the positivity assumption in the context of assessing model and parameter specific identifiability of causal effects. Positivity violations occur when certain subgroups in a sample rarely or never receive some treatments of interest. The resulting sparsity in the data may increase bias with or without an increase in variance and can threaten valid inference. The parametric bootstrap is presented as a tool to assess the severity of such threats and its utility as a diagnostic is explored using simulated and real data. Several approaches for improving the identifiability of parameters in the presence of positivity violations are reviewed. Potential responses to data sparsity include restriction of the covariate adjustment set, use of an alternative projection function to define the target parameter within a marginal structural working model, restriction of the sample, and modification of the target intervention. All of these approaches can be understood as trading off proximity to the initial target of inference for identifiability; we advocate approaching this tradeoff systematically. PMID- 21030424 TI - DMS cyclone separation processes for optimization of plastic wastes recycling and their implications. AB - It is demonstrated that substantial reductions in plastics presently disposed of in landfills can be achieved by cyclone density media separation (DMS). In comparison with the size fraction of plastics presently processed by industrial density separations (generally 6.4 to 9.5 mm), cyclone DMS methods are demonstrated to effectively process a substantially greater range of particle sizes (from 0.5 up to 120 mm). The purities of plastic products and recoveries obtained with a single stage separation using a cylindrical cyclone are shown to attain virtually 100% purity and recoveries >99% for high-density fractions and >98% purity and recoveries were obtained for low-density products. Four alternative schemas of multi-stage separations are presented and analyzed as proposed methods to obtain total low- and high-density plastics fraction recoveries while maintaining near 100% purities. The results of preliminary tests of two of these show that the potential for processing product purities and recoveries >99.98% of both density fractions are indicated. A preliminary economic comparison of capital costs of DMS systems suggests cyclone DMS methods to be comparable with other DMS processes even if the high volume capacity for recycling operations of these is not optimized. PMID- 21030421 TI - Towards improved animal models of neonatal white matter injury associated with cerebral palsy. AB - Newborn neurological injuries are the leading cause of intellectual and motor disabilities that are associated with cerebral palsy. Cerebral white matter injury is a common feature in hypoxic-ischemic encephalopathy (HIE), which affects full-term infants, and in periventricular leukomalacia (PVL), which affects preterm infants. This article discusses recent efforts to model neonatal white matter injury using mammalian systems. We emphasize that a comprehensive understanding of oligodendrocyte development and physiology is crucial for obtaining new insights into the pathobiology of HIE and PVL as well as for the generation of more sophisticated and faithful animal models. PMID- 21030425 TI - Long term monitoring of leachate flux into drainage pipes of MSW landfills. AB - The measurement of leachate quality and quantity is an essential part of the monitoring of landfills in the different phases during their lifespan. These measurements allow the evaluation of the decomposition processes in the landfill and the efficiency of technical installations for the reduction of the leachate generation. Normally the measurements are made at the outlet of larger sections of the landfill or at the overall landfill. An identification of smaller parts with different biological or hydraulic behaviour within the landfill section is not possible in that case. In the framework of a long-term research project concerning the monitoring of landfills, different devices for small-scale identification of the leachate discharge were developed at the Technical University of Braunschweig. The device allows a measurement of the leachate discharge inside a single drainage pipe having a length up to 375 m. The measurements showed the influence of changes in operation. It was found that the discharge in the pipes and the efficiency of the drainage system was strongly influenced by deformations and torsion of the high-density polyethylene pipes and unequal settlements of the subsoil. The discharge of leachate in the drainage system was, as expected, very non-uniform and in parts the leachate was not flowing inside the pipes, but rather in the surrounding gravel layer. Furthermore, large differences in leachate quality may occur, whereas the differences in discharge volume are small. With the developed system it is possible to control the efficiency and the functioning of top cover systems for landfills. PMID- 21030426 TI - Genetic variations in Tibetan populations and high-altitude adaptation at the Himalayas. AB - Modern humans have occupied almost all possible environments globally since exiting Africa about 100,000 years ago. Both behavioral and biological adaptations have contributed to their success in surviving the rigors of climatic extremes, including cold, strong ultraviolet radiation, and high altitude. Among these environmental stresses, high-altitude hypoxia is the only condition in which traditional technology is incapable of mediating its effects. Inhabiting at >3,000-m high plateau, the Tibetan population provides a widely studied example of high-altitude adaptation. Yet, the genetic mechanisms underpinning long-term survival in this environmental extreme remain unknown. We performed an analysis of genome-wide sequence variations in Tibetans. In combination with the reported data, we identified strong signals of selective sweep in two hypoxia-related genes, EPAS1 and EGLN1. For these two genes, Tibetans show unusually high divergence from the non-Tibetan lowlanders (Han Chinese and Japanese) and possess high frequencies of many linked sequence variations as reflected by the Tibetan specific haplotypes. Further analysis in seven Tibetan populations (1,334 individuals) indicates the prevalence of selective sweep across the Himalayan region. The observed indicators of natural selection on EPAS1 and EGLN1 suggest that during the long-term occupation of high-altitude areas, the functional sequence variations for acquiring biological adaptation to high-altitude hypoxia have been enriched in Tibetan populations. PMID- 21030427 TI - Phylogenomic analysis of kinetoplastids supports that trypanosomatids arose from within bodonids. AB - Kinetoplastids are a large group of free-living and parasitic eukaryotic flagellates, including the medically important trypanosomatids (e.g., Trypanosoma and Leishmania) and the widespread free-living and parasitic bodonids. Small subunit rRNA- and conserved protein-based phylogenies support the division of kinetoplastids into five orders (Prokinetoplastida, Neobodonida, Parabodonida, Eubodonida, and Trypanosomatida), but they produce incongruent results regarding their relative branching order, in particular for the position of the Trypanosomatida. In general, small subunit rRNA tends to support their early emergence, whereas protein phylogenies most often support a more recent origin from within bodonids. In order to resolve this question through a phylogenomic approach, we carried out massive parallel sequencing of cDNA from representatives of three bodonid orders (Bodo saltans -Eubodonida-, Procryptobia sorokini Parabodonida-, and Rhynchomonas nasuta -Neobodonida-). We identified 64 well conserved proteins shared by these species, four trypanosomatids, and two closely related outgroup species (Euglena gracilis and Diplonema papillatum). Phylogenetic analysis of a concatenated data set yielded a strongly supported tree showing the late emergence of trypanosomatids as a sister group of the Eubodonida. In addition, we identified homologues of proteins involved in trypanosomatid mitochondrial mRNA editing in the three bodonid species, suggesting that editing may be widespread in kinetoplastids. Comparison of expressed sequences from mitochondrial genes showed variability at U positions, in agreement with the existence of editing activity in the three bodonid orders most closely related to trypanosomatids (Neobodonida, Parabodonida, and Eubodonida). Mitochondrial mRNA editing appears to be an ancient phenomenon in kinetoplastids. PMID- 21030428 TI - Disease transmission in territorial populations: the small-world network of Serengeti lions. AB - Territoriality in animal populations creates spatial structure that is thought to naturally buffer disease invasion. Often, however, territorial populations also include highly mobile, non-residential individuals that potentially serve as disease superspreaders. Using long-term data from the Serengeti Lion Project, we characterize the contact network structure of a territorial wildlife population and address the epidemiological impact of nomadic individuals. As expected, pride contacts are dominated by interactions with neighbouring prides and interspersed by encounters with nomads as they wander throughout the ecosystem. Yet the pride pride network also includes occasional long-range contacts between prides, making it surprisingly small world and vulnerable to epidemics, even without nomads. While nomads increase both the local and global connectivity of the network, their epidemiological impact is marginal, particularly for diseases with short infectious periods like canine distemper virus. Thus, territoriality in Serengeti lions may be less protective and non-residents less important for disease transmission than previously considered. PMID- 21030429 TI - Adaptations for economical bipedal running: the effect of limb structure on three dimensional joint mechanics. AB - The purpose of this study was to examine the mechanical adaptations linked to economical locomotion in cursorial bipeds. We addressed this question by comparing mass-matched humans and avian bipeds (ostriches), which exhibit marked differences in limb structure and running economy. We hypothesized that the nearly 50 per cent lower energy cost of running in ostriches is a result of: (i) lower limb-swing mechanical power, (ii) greater stance-phase storage and release of elastic energy, and (iii) lower total muscle power output. To test these hypotheses, we used three-dimensional joint mechanical measurements and a simple model to estimate the elastic and muscle contributions to joint work and power. Contradictory to our first hypothesis, we found that ostriches and humans generate the same amounts of mechanical power to swing the limbs at a similar self-selected running speed, indicating that limb swing probably does not contribute to the difference in energy cost of running between these species. In contrast, we estimated that ostriches generate 120 per cent more stance-phase mechanical joint power via release of elastic energy compared with humans. This elastic mechanical power occurs nearly exclusively at the tarsometatarso phalangeal joint, demonstrating a shift of mechanical power generation to distal joints compared with humans. We also estimated that positive muscle fibre power is 35 per cent lower in ostriches compared with humans, and is accounted for primarily by higher capacity for storage and release of elastic energy. Furthermore, our analysis revealed much larger frontal and internal/external rotation joint loads during ostrich running than in humans. Together, these findings support the hypothesis that a primary limb structure specialization linked to economical running in cursorial species is an elevated storage and release of elastic energy in tendon. In the ostrich, energy-saving specializations may also include passive frontal and internal/external rotation load-bearing mechanisms. PMID- 21030430 TI - Dose-response assessment of nephrotoxicity from a 7-day combined exposure to melamine and cyanuric acid in F344 rats. AB - The intentional adulteration of pet food with melamine and derivatives, including cyanuric acid, has been implicated in the kidney failure and death of a large number of cats and dogs in the United States. Although individually these compounds present low toxicity, coexposure can lead to the formation of melamine cyanurate crystals in the nephrons and eventual kidney failure. To determine the dose-response for nephrotoxicity upon coadministration of melamine and cyanuric acid, groups of male and female F344 rats (six animals per sex per group) were fed 0 (control), 7, 23, 69, 229, or 694 ppm of both melamine and cyanuric acid; 1388 ppm melamine; or 1388 ppm cyanuric acid in the diet for 7 days. No toxicity was observed in the rats exposed to the individual compounds, whereas anorexia and a statistically significant increase in blood urea nitrogen and serum creatinine levels was observed in the animals treated with 229 and 694 ppm melamine and cyanuric acid. The kidneys of these animals were grossly enlarged and pale yellow. Large numbers of crystalline structures deposited in the tubules were seen on sections in kidneys from all rats in these treatment groups. No significant changes were detected in the remaining treatment groups exposed to both melamine and cyanuric acid. In the melamine-only treatment group, 5 of 12 rats had scattered crystals present in renal tubules when examined by wet mount. These were not observed by histopathology. The observed adverse effect level (8.6 mg/kg bw [body weight]/day) and benchmark dose modeling data (8.4-10.9 mg/kg bw/day) determined in this study suggest that the tolerable daily intake values derived from studies conducted with melamine alone may underestimate the risk from coexposures to melamine and cyanuric acid. PMID- 21030431 TI - Brain. Editorial. PMID- 21030432 TI - Successful 'passive transfer' of paraneoplastic stiff person syndrome with antibodies to an intracellular antigen. PMID- 21030433 TI - Role of the phenazine-inducing protein Pip in stress resistance of Pseudomonas chlororaphis. AB - The triggering of antibiotic production by various environmental stress molecules can be interpreted as bacteria's response to obtain increased fitness to putative danger, whereas the opposite situation - inhibition of antibiotic production - is more complicated to understand. Phenazines enable Pseudomonas species to eliminate competitors for rhizosphere colonization and are typical virulence factors used for model studies. In the present work, we have investigated the negative effect of subinhibitory concentrations of NaCl, fusaric acid and two antibiotics on quorum-sensing-controlled phenazine production by Pseudomonas chlororaphis. The selected stress factors inhibit phenazine synthesis despite sufficient cell density. Subsequently, we have identified connections between known genes of the phenazine-inducing cascade, including PsrA (Pseudomonas sigma regulator), RpoS (alternative sigma factor), Pip (phenazine inducing protein) and PhzI/PhzR (quorum-sensing system). Under all tested conditions, overexpression of Pip or PhzR restored phenazine production while overexpression of PsrA or RpoS did not. This forced restoration of phenazine production in strains overexpressing regulatory genes pip and phzR significantly impairs growth and stress resistance; this is particularly severe with pip overexpression. We suggest a novel physiological explanation for the inhibition of phenazine virulence factors in pseudomonas species responding to toxic compounds. We propose that switching off phenazine-1-carboxamide (PCN) synthesis by attenuating pip expression would favour processes required for survival. In our model, this 'decision' point for promoting PCN production or stress resistance is located downstream of rpoS and just above pip. However, a test with the stress factor rifampicin shows no significant inhibition of Pip production, suggesting that stress factors may also target other and so far unknown protagonists of the PCN signalling cascade. PMID- 21030434 TI - Immunoreactive Coxiella burnetii Nine Mile proteins separated by 2D electrophoresis and identified by tandem mass spectrometry. AB - Coxiella burnetii is a Gram-negative obligate intracellular pathogen and the causative agent of Q fever in humans. Q fever causes acute flu-like symptoms and may develop into a chronic disease leading to endocarditis. Its potential as a bioweapon has led to its classification as a category B select agent. An effective inactivated whole-cell vaccine (WCV) currently exists but causes severe granulomatous/necrotizing reactions in individuals with prior exposure, and is not licensed for use in most countries. Current efforts to reduce or eliminate the deleterious reactions associated with WCVs have focused on identifying potential subunit vaccine candidates. Both humoral and T cell-mediated responses are required for protection in animal models. In this study, nine novel immunogenic C. burnetii proteins were identified in extracted whole-cell lysates using 2D electrophoresis, immunoblotting with immune guinea pig sera, and tandem MS. The immunogenic C. burnetii proteins elicited antigen-specific IgG in guinea pigs vaccinated with whole-cell killed Nine Mile phase I vaccine, suggesting a T cell-dependent response. Eleven additional proteins previously shown to react with immune human sera were also antigenic in guinea pigs, showing the relevance of the guinea pig immunization model for antigen discovery. The antigens described here warrant further investigation to validate their potential use as subunit vaccine candidates. PMID- 21030435 TI - The cell envelope stress response mediated by the LiaFSRLm three-component system of Listeria monocytogenes is controlled via the phosphatase activity of the bifunctional histidine kinase LiaSLm. AB - Most members of the phylum Firmicutes harbour a two-component system (TCS), LiaSR, which is involved in the response to cell envelope stress elicited most notably by inhibitors of the lipid II cycle. In all LiaSR systems studied in detail, LiaSR-mediated signal transduction has been shown to be negatively controlled by a membrane protein, LiaF, encoded upstream of liaSR. In this study we have analysed the LiaSR orthologue of Listeria monocytogenes (LiaSR(Lm)). Whole-genome transcriptional profiling indicated that activation of LiaSR(Lm) results in a remodelling of the cell envelope via the massive upregulation of membrane-associated and extracytoplasmic proteins in the presence of inducing stimuli. As shown for other LiaSR TCSs, LiaSR(Lm) is activated by cell wall active antibiotics. We demonstrate that the level of phosphorylated LiaR(Lm), which is required for the induction of the LiaSR(Lm) regulon, is controlled by the interplay between the histidine kinase and phosphatase activities of the bifunctional sensor protein LiaS(Lm). Our data suggest that the phosphatase activity of LiaS(Lm) is stimulated by LiaF(Lm) in the absence of cell envelope stress. PMID- 21030436 TI - Txe, an endoribonuclease of the enterococcal Axe-Txe toxin-antitoxin system, cleaves mRNA and inhibits protein synthesis. AB - The axe-txe operon encodes a toxin-antitoxin (TA) pair, Axe-Txe, that was initially identified on the multidrug-resistance plasmid pRUM in Enterococcus faecium. In Escherichia coli, expression of the Txe toxin is known to inhibit cell growth, and co-expression of the antitoxin, Axe, counteracts the toxic effect of Txe. Here, we report the nucleotide sequence of pS177, a 39 kb multidrug-resistant plasmid isolated from vancomycin-resistant Ent. faecium, which harbours the axe-txe operon and the vanA gene cluster. RT-PCR analysis revealed that the axe-txe transcript is produced by strain S177 as well as by other vancomycin-resistant enteroccoci. Moreover, we determine the mechanism by which the Txe protein exerts its toxic activity. Txe inhibits protein synthesis in E. coli without affecting DNA or RNA synthesis, and inhibits protein synthesis in a cell-free system. Using in vivo primer extension analysis, we demonstrate that Txe preferentially cleaves single-stranded mRNA at the first base after an AUG start codon. We conclude that Txe is an endoribonuclease which cleaves mRNA and inhibits protein synthesis. PMID- 21030437 TI - IEDB-3D: structural data within the immune epitope database. AB - IEDB-3D is the 3D structural component of the Immune Epitope Database (IEDB) available via the 'Browse by 3D Structure' page at http://www.iedb.org. IEDB-3D catalogs B- and T-cell epitopes and Major Histocompatibility Complex (MHC) ligands for which 3D structures of complexes with antibodies, T-cell receptors or MHC molecules are available in the Protein Data Bank (PDB). Journal articles that are primary citations of PDB structures and that define immune epitopes are curated within IEDB as any other reference along with accompanying functional assays and immunologically relevant information. For each curated structure, IEDB 3D provides calculated data on intermolecular contacts and interface areas and includes an application, EpitopeViewer, to visualize the structures. IEDB-3D is fully embedded within IEDB, thus allowing structural data, both curated and calculated, and all accompanying information to be queried using multiple search interfaces. These include queries for epitopes recognized in different pathogens, eliciting different functional immune responses, and recognized by different components of the immune system. The query results can be downloaded in Microsoft Excel format, or the entire database, together with structural data both curated and calculated, can be downloaded in either XML or MySQL formats. PMID- 21030438 TI - Mapping of long-range associations throughout the fission yeast genome reveals global genome organization linked to transcriptional regulation. AB - We have comprehensively mapped long-range associations between chromosomal regions throughout the fission yeast genome using the latest genomics approach that combines next generation sequencing and chromosome conformation capture (3C). Our relatively simple approach, referred to as enrichment of ligation products (ELP), involves digestion of the 3C sample with a 4 bp cutter and self ligation, achieving a resolution of 20 kb. It recaptures previously characterized genome organizations and also identifies new and important interactions. We have modeled the 3D structure of the entire fission yeast genome and have explored the functional relationships between the global genome organization and transcriptional regulation. We find significant associations among highly transcribed genes. Moreover, we demonstrate that genes co-regulated during the cell cycle tend to associate with one another when activated. Remarkably, functionally defined genes derived from particular gene ontology groups tend to associate in a statistically significant manner. Those significantly associating genes frequently contain the same DNA motifs at their promoter regions, suggesting that potential transcription factors binding to these motifs are involved in defining the associations among those genes. Our study suggests the presence of a global genome organization in fission yeast that is functionally similar to the recently proposed mammalian transcription factory. PMID- 21030439 TI - A multivalent DNA aptamer specific for the B-cell receptor on human lymphoma and leukemia. AB - Long-term survival still eludes most patients with leukemia and non-Hodgkin's lymphoma. No approved therapies target the hallmark of the B cell, its mIgM, also known as the B-cell receptor (BCR). Aptamers are small oligonucleotides that can specifically bind to a wide range of target molecules and offer some advantages over antibodies as therapeutic agents. Here, we report the rational engineering of aptamer TD05 into multimeric forms reactive with the BCR that may be useful in biomedical applications. Systematic truncation of TD05 coupled with modification with locked nucleic acids (LNA) increased conformational stability and nuclease resistance. Trimeric and tetrameric versions with optimized polyethyleneglycol (PEG) linker lengths exhibited high avidity at physiological temperatures both in vitro and in vivo. Competition and protease studies showed that the multimeric, optimized aptamer bound to membrane-associated human mIgM, but not with soluble IgM in plasma, allowing the possibility of targeting leukemias and lymphomas in vivo. The B-cell specificity of the multivalent aptamer was confirmed on lymphoma cell lines and fresh clinical leukemia samples. The chemically engineered aptamers, with significantly improved kinetic and biochemical features, unique specificity and desirable pharmacological properties, may be useful in biomedical applications. PMID- 21030441 TI - The BRENDA Tissue Ontology (BTO): the first all-integrating ontology of all organisms for enzyme sources. AB - BTO, the BRENDA Tissue Ontology (http://www.BTO.brenda-enzymes.org) represents a comprehensive structured encyclopedia of tissue terms. The project started in 2003 to create a connection between the enzyme data collection of the BRENDA enzyme database and a structured network of source tissues and cell types. Currently, BTO contains more than 4600 different anatomical structures, tissues, cell types and cell lines, classified under generic categories corresponding to the rules and formats of the Gene Ontology Consortium and organized as a directed acyclic graph (DAG). Most of the terms are endowed with comments on their derivation or definitions. The content of the ontology is constantly curated with ~1000 new terms each year. Four different types of relationships between the terms are implemented. A versatile web interface with several search and navigation functionalities allows convenient online access to the BTO and to the enzymes isolated from the tissues. Important areas of applications of the BTO terms are the detection of enzymes in tissues and the provision of a solid basis for text-mining approaches in this field. It is widely used by lab scientists, curators of genomic and biochemical databases and bioinformaticians. The BTO is freely available at http://www.obofoundry.org. PMID- 21030440 TI - Meiotic recombination protein Rec12: functional conservation, crossover homeostasis and early crossover/non-crossover decision. AB - In fission yeast and other eukaryotes, Rec12 (Spo11) is thought to catalyze the formation of dsDNA breaks (DSBs) that initiate homologous recombination in meiosis. Rec12 is orthologous to the catalytic subunit of topoisomerase VI (Top6A). Guided by the crystal structure of Top6A, we engineered the rec12 locus to encode Rec12 proteins each with a single amino acid substitution in a conserved residue. Of 21 substitutions, 10 significantly reduced or abolished meiotic DSBs, gene conversion, crossover recombination and the faithful segregation of chromosomes. Critical residues map within the metal ion-binding pocket toprim (E179A, D229A, D231A), catalytic region 5Y-CAP (R94A, D95A, Y98F) and the DNA-binding interface (K201A, G202E, R209A, K242A). A subset of substitutions reduced DSBs but maintained crossovers, demonstrating crossover homeostasis. Furthermore, a strong separation of function mutation (R304A) suggests that the crossover/non-crossover decision is established early by a protein-protein interaction surface of Rec12. Fission yeast has multiple crossovers per bivalent, and chromosome segregation was robust above a threshold of about one crossover per bivalent, below which non-disjunction occurred. These results support structural and functional conservation among Rec12/Spo11/Top6A family members for the catalysis of DSBs, and they reveal how Rec12 regulates other features of meiotic chromosome dynamics. PMID- 21030442 TI - Synergism between DNA methylation and macroH2A1 occupancy in epigenetic silencing of the tumor suppressor gene p16(CDKN2A). AB - Promoter hypermethylation and heterochromatinization is a frequent event leading to gene inactivation and tumorigenesis. At the molecular level, inactivation of tumor suppressor genes in cancer has many similarities to the inactive X chromosome in female cells and is defined and maintained by DNA methylation and characteristic histone modifications. In addition, the inactive-X is marked by the histone macroH2A, a variant of H2A with a large non-histone region of unknown function. Studying tumor suppressor genes (TSGs) silenced in cancer cell lines, we find that when active, these promoters are associated with H2A.Z but become enriched for macroH2A1 once silenced. Knockdown of macroH2A1 was not sufficient for reactivation of silenced genes. However, when combined with DNA demethylation, macroH2A1 deficiency significantly enhanced reactivation of the tumor suppressor genes p16, MLH1 and Timp3 and inhibited cell proliferation. Our findings link macroH2A1 to heterochromatin of epigenetically silenced cancer genes and indicate synergism between macroH2A1 and DNA methylation in maintenance of the silenced state. PMID- 21030444 TI - Decision rules in diagnosing subarachnoid haemorrhage. PMID- 21030447 TI - Moving to smaller commissioning units flies in face of international evidence on effectiveness. PMID- 21030443 TI - High risk clinical characteristics for subarachnoid haemorrhage in patients with acute headache: prospective cohort study. AB - OBJECTIVE: To identify high risk clinical characteristics for subarachnoid haemorrhage in neurologically intact patients with headache. DESIGN: Multicentre prospective cohort study over five years. SETTING: Six university affiliated tertiary care teaching hospitals in Canada. Data collected from November 2000 until November 2005. PARTICIPANTS: Neurologically intact adults with a non traumatic headache peaking within an hour. MAIN OUTCOME MEASURES: Subarachnoid haemorrhage, as defined by any of subarachnoid haemorrhage on computed tomography of the head, xanthochromia in the cerebrospinal fluid, or red blood cells in the final sample of cerebrospinal fluid with positive results on angiography. Physicians completed data collection forms before investigations. RESULTS: In the 1999 patients enrolled there were 130 cases of subarachnoid haemorrhage. Mean (range) age was 43.4 (16-93), 1207 (60.4%) were women, and 1546 (78.5%) reported that it was the worst headache of their life. Thirteen of the variables collected on history and three on examination were reliable and associated with subarachnoid haemorrhage. We used recursive partitioning with different combinations of these variables to create three clinical decisions rules. All had 100% (95% confidence interval 97.1% to 100.0%) sensitivity with specificities from 28.4% to 38.8%. Use of any one of these rules would have lowered rates of investigation (computed tomography, lumbar puncture, or both) from the current 82.9% to between 63.7% and 73.5%. CONCLUSION: Clinical characteristics can be predictive for subarachnoid haemorrhage. Practical and sensitive clinical decision rules can be used in patients with a headache peaking within an hour. Further study of these proposed decision rules, including prospective validation, could allow clinicians to be more selective and accurate when investigating patients with headache. PMID- 21030448 TI - Group is launched to present "hard evidence" against physician assisted suicide. PMID- 21030449 TI - Increased epithelial permeability in pulmonary fibrosis in relation to disease progression. AB - Epithelial injury contributes to pathogenesis in idiopathic pulmonary fibrosis (IPF) but its role in the interstitial lung disease (ILD) of systemic sclerosis (SSc) is uncertain. We quantified the prognostic significance of inhaled technetium-99m ((99m)Tc)-labelled diethylene triamine pentacetate (DTPA) pulmonary clearance, a marker of the extent of epithelial injury, in both diseases. Baseline (99m)Tc-DTPA pulmonary clearance was evaluated retrospectively in patients with SSc-ILD (n = 168) and IPF (n = 97) against mortality and disease progression. In SSc-ILD, the rapidity of total clearance (hazard ratio (HR) 1.02, 95% CI 1.01-1.03; p = 0.001) and the presence of abnormally rapid clearance (HR 2.10; 95% CI 1.25-3.53; p = 0.005) predicted a shorter time to forced vital capcity (FVC) decline, independent of disease severity. These associations were robust in both mild and severe disease. By contrast, in IPF, delayed clearance of the slow component, an expected consequence of honeycomb change, was an independent predictor of a shorter time to FVC decline (HR 1.01, 95% CI 1.00 1.02; p<0.01). Epithelial injury should be incorporated in pathogenetic models in SSc-ILD. By contrast, outcome is not linked to the overall extent of epithelial injury in IPF, apart from abnormalities ascribable to honeycombing, suggesting that core pathogenetic events may be more spatially focal in that disease. PMID- 21030450 TI - Assessment of problematic severe asthma in children. AB - Assessment of problematic severe asthma in children should be performed in a step wise manner to ensure an optimal approach. A four-step assessment scheme is proposed. First, a full diagnostic work-up is performed to exclude other diseases which mimic asthma. Secondly, a multi-disciplinary assessment is performed to identify issues that may need attention, including comorbidities. Thirdly, the pattern of inflammation is assessed, and finally steroid responsiveness is documented. Based upon these four steps an optimal individualised treatment plan is developed. In this article the many gaps in our current knowledge in all these steps are highlighted, and recommendations for current clinical practice and future research are made. The lack of good data and the heterogeneity of problematic severe asthma still limit our ability to optimise the management on an individual basis in this small, but challenging group of patients. PMID- 21030451 TI - Interferon-gamma release assays for the diagnosis of latent Mycobacterium tuberculosis infection: a systematic review and meta-analysis. AB - We conducted a systematic review and meta-analysis to compare the accuracy of the QuantiFERON-TB(r) Gold In-Tube (QFT-G-IT) and the T-SPOT(r).TB assays with the tuberculin skin test (TST) for the diagnosis of latent Mycobacterium tuberculosis infection (LTBI). The Medline, Embase and Cochrane databases were explored for relevant articles in November 2009. Specificities, and negative (NPV) and positive (PPV) predictive values of interferon-gamma release assays (IGRAs) and the TST, and the exposure gradient influences on test results among bacille Calmette-Guerin (BCG) vaccinees were evaluated. Specificity of IGRAs varied 98 100%. In immunocompetent adults, NPV for progression to tuberculosis within 2 yrs were 97.8% for T-SPOT(r).TB and 99.8% for QFT-G-IT. When test performance of an immunodiagnostic test was not restricted to prior positivity of another test, progression rates to tuberculosis among IGRA-positive individuals followed for 19 24 months varied 8-15%, exceeding those reported for the TST (2-3%). In multivariate analyses, the odd ratios for TST positivity following BCG vaccination varied 3-25, whereas IGRA results remained uninfluenced and IGRA positivity was clearly associated with exposure to contagious tuberculosis cases. IGRAs may have a relative advantage over the TST in detecting LTBI and allow the exclusion of M. tuberculosis infection with higher reliability. PMID- 21030452 TI - Influence of hay and animal feed exposure on respiratory status: a longitudinal study. AB - Our aim was to study respiratory symptoms and lung function decline in farmers, with particular attention to the influence of handling hay, straw and animal feed. From a cohort recruited in 1993-1994, 219 (82.6%) dairy farmers, 130 (62.5%) nondairy agricultural workers and 99 (66.4%) controls were re-evaluated in 2006. They answered medical and occupational questionnaires, underwent spirometric tests at both evaluations and pulse oximetry in 2006. Dairy and nondairy agricultural workers showed an increased risk for usual morning phlegm (adjusted OR 4.27 (95% CI 1.41-12.95) and 3.59 (95% CI 1.16-11.10), respectively). Animal feed handling was associated with increased risks of wheezing (p = 0.01) and usual morning phlegm (p = 0.04); hay or straw handling was associated with increased risk of wheezing (p = 0.008). Adjusting for smoking, age, height, sex and altitude, dairy farmers had greater declines in forced expiratory volume in 1 s (FEV(1))/forced vital capacity ratio (p = 0.01) than controls. An increased decline in FEV(1) for all agricultural workers was associated with animal feed handling, both measured as a categorical (currently versus never handling; p = 0.05) or quantitative value (years of exposure during the survey period; p = 0.03). Hay, straw or animal feed handling represents a risk factor of bronchial symptoms and, for animal feed only, of accelerated decline in expiratory flows. PMID- 21030453 TI - Genetic profiling and epidermal growth factor receptor-directed therapy in nonsmall cell lung cancer. AB - The principle of preferentially selecting patients most likely to benefit from therapy according to their genetic profile has led to substantial clinical benefit in some tumour types, and has potential to considerably refine treatment in advanced nonsmall cell lung cancer (NSCLC). Effective, reliable use of molecular biomarkers to inform clinical practice requires the standardisation of testing methods and careful assessment of biomarkers' predictive and prognostic value. Although a number of studies have shown that patients with activating mutations in exons 18-21 of the epidermal growth factor receptor (EGFR) gene respond particularly well to gefitinib and erlotinib, a prospective, randomised study was needed to differentiate between the prognostic and predictive value of EGFR mutations. From one such study, it appeared that mutational testing should become standard at diagnosis, at least for adenocarcinoma patients with a never or low smoking history, as clinical predictors are insufficient to optimise treatment. However, outstanding questions remain: what are the treatment options for patients with tumours resistant to erlotinib/gefitinib? What conclusions about treatment can we draw from EGFR copy number or KRAS mutation status? What role should anti-EGFR antibodies play in NSCLC treatment, and in which patients? This review considers current evidence linking biomarker profile to efficacy of EGFR-targeted therapy in NSCLC, and clinical implications of recent findings. PMID- 21030454 TI - Exposure to combustion of solid fuel and tuberculosis: a matched case-control study. AB - The present study was conducted in Benin to ascertain the association between exposure to combustion of solid fuel (coal and biomass) and tuberculosis. Cases were consecutive, sputum smear-positive tuberculosis patients never previously treated for tuberculosis for as long as 1 month. Two controls were selected from the neighbourhood of each case, matched by age and sex by a predefined procedure. A total of 200 new smear-positive cases and 400 neighbourhood controls were enrolled. In univariate analysis, using solid fuel for cooking (OR 1.7, 95% CI 1.1-2.8), ever smoking (OR 5.5, 95% CI 3.1-9.8), male sex (OR 10.5, 95% CI 1.6 71.1), daily use of alcoholic beverages (OR 2.3, 95% CI 1.2-4.2) and having a family member with tuberculosis in the previous 5 yrs (OR 30.5, 95% CI 10.8-85.8) were all significantly associated with tuberculosis cases. When all significant variables were entered into a multivariate conditional logistic regression model, the association between using solid fuel for cooking and tuberculosis cases was no longer statistically significant (adjusted OR 1.4, 95% CI 0.7-2.7). In conclusion, the association between exposure to combustion of solid fuel and tuberculosis was relatively weak and not statistically significant. PMID- 21030455 TI - Stressful life events and the onset of asthma. AB - The status of stressful life events as a risk factor for asthma is unclear and may be dependent on pre-existing allergic rhinitis. This study examined whether exposure to stressful life events predicted the onset of asthma in adults. This is a prospective, population-based cohort study of 16,881 males and females, aged 20-54 yrs and free of diagnosed asthma at the beginning of the follow-up (January 1, 2004). Data about stressful life events were gathered with a postal survey. The onset of asthma was ascertained through national registers until December 31, 2005. During the follow-up period, 192 incident cases of asthma were identified. High total exposure to stressful life events, as indicated by a cumulative severity score, predicted the onset of asthma (hazard ratio 1.96, 95% CI 1.22 3.13). This association was robust to adjustment for demographics, smoking and having a cat/dog at home and it was observed both among those with and without allergic rhinitis at baseline. Of the 10 most stressful life events, the illness of a family member, marital problems, divorce or separation and conflicts with a supervisor were associated with the onset of asthma. Our study suggests that stressful life events may increase the onset of asthma. PMID- 21030456 TI - Evidence that onset of psychosis in the population reflects early hallucinatory experiences that through environmental risks and affective dysregulation become complicated by delusions. AB - OBJECTIVE: To examine the hypothesis that the "natural" combination of delusions and hallucinations in psychotic disorders in fact represents a selection of early subclinical hallucinatory experiences associated with delusional ideation, resulting in need for care and mental health service use. METHODS: In the Early Developmental Stages of Psychopathology study, a prospective, 10-year follow-up of a representative cohort of adolescents and young adults in Munich, Germany (n = 2524), clinical psychologists assessed hallucinations and delusions at 2 time points (T2 and T3). Analyses compared differences in psychopathology, familial liability for nonpsychotic disorder, nongenetic risk factors, persistence, and clinical outcome between groups characterized by: (1) absence of positive psychotic symptoms, (2) presence of isolated hallucinations, (3) isolated delusions, and (4) both hallucinations and delusions. RESULTS: Delusions and hallucinations occurred together much more often (T2: 3.1%; T3: 2.0%) than predicted by chance (T2: 1.0%; T3: 0.4%; OR = 11.0; 95% CI: 8.1, 15.1). Content of delusions was contingent on presence of hallucinations but modality of hallucinations was not contingent on presence of delusions. The group with both hallucinations and delusions, compared to groups with either delusions or hallucinations in isolation, displayed the strongest associations with familial affective liability and nongenetic risk factors, as well as with persistence of psychotic symptoms, comorbidity with negative symptoms, affective psychopathology, and clinical need. CONCLUSIONS: The early stages of psychosis may involve hallucinatory experiences that, if complicated by delusional ideation under the influence of environmental risks and (liability for) affective dysregulation, give rise to a poor prognosis hallucinatory-delusional syndrome. PMID- 21030457 TI - Comparison of the rapid methods for screening of group a rotavirus in stool samples. AB - In this study, the sensitivity and specificity of three immunochromatography (IC) test kits for rapid detection of group A rotavirus were compared and evaluated with stool samples collected from children, who suffered from acute gastroenteritis during February to June, 2009 in Japan. A total of 86 stool samples were tested and compared with a reference RT-PCR method. The sensitivity among IP-Rota V, Dipstick Eiken ROTA and ROTA-ADENO test kits were 97.2, 95.8 and 88.7%, while the specificity were 100, 93.3 and 100%, respectively. It was demonstrated that the IC kits evaluated in this study could be used as an alternative method for the rapid screening of group A rotavirus in fecal specimens, especially during acute gastroenteritis outbreak season. PMID- 21030458 TI - Relationship of visceral and subcutaneous adiposity with renal function in people with type 2 diabetes mellitus. AB - BACKGROUND: Obesity and diabetes mellitus (DM) are established risk factors for the development of chronic kidney disease. Visceral adiposity (VAT) and subcutaneous adiposity (SAT) may be associated with the differential metabolic risk. Our study was performed to determine whether VAT or SAT was associated with the decrease of renal function in people with type 2 DM. METHODS: Nine hundred and twenty-nine people with type 2 DM and who had undergone abdominal computed tomography assessment of the SAT and VAT areas were included. The estimated glomerular filtration rate (eGFR) was calculated using the Cockcroft-Gault equation and the Modification of Diet in Renal Disease (MDRD) four-variable equation at the time of the assessment of the SAT and VAT areas. RESULTS: VAT was negatively associated with eGFR using the MDRD equation after adjustment for the clinical variables (beta-coefficient = - 0.075, P = 0.034), while SAT was not significantly associated with eGFR. There was no significant association between the abdominal adiposity measurements and the eGFR using the Cockcroft-Gault formula. When stratifying the individuals by the body mass index groups, VAT was negatively associated with eGFR by the MDRD equation and the Cockcroft-Gault formula in the overweight and obese subjects after adjustment for the clinical variables, while there was no significant association between the VAT and the eGFR in the normal weight subjects. SAT was not significantly associated with eGFR in the normal weight, overweight and obese subjects. CONCLUSIONS: Our data suggest that VAT may be an additional prognostic factor for the decrease of renal function especially in the overweight or obese subjects with type 2 DM. PMID- 21030460 TI - Statistical distribution of amino acid sequences: a proof of Darwinian evolution. AB - MOTIVATION: The article presents results of the listing of the quantity of amino acids, dipeptides and tripeptides for all proteins available in the UNIPROT TREMBL database and the listing for selected species and enzymes. UNIPROT-TREMBL contains protein sequences associated with computationally generated annotations and large-scale functional characterization. Due to the distinct metabolic pathways of amino acid syntheses and their physicochemical properties, the quantities of subpeptides in proteins vary. We have proved that the distribution of amino acids, dipeptides and tripeptides is statistical which confirms that the evolutionary biodiversity development model is subject to the theory of independent events. It seems interesting that certain short peptide combinations occur relatively rarely or even not at all. First, it confirms the Darwinian theory of evolution and second, it opens up opportunities for designing pharmaceuticals among rarely represented short peptide combinations. Furthermore, an innovative approach to the mass analysis of bioinformatic data is presented. CONTACT: eitner@amu.edu.pl SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 21030459 TI - The neuroblastoma-associated F1174L ALK mutation causes resistance to an ALK kinase inhibitor in ALK-translocated cancers. AB - The ALK kinase inhibitor crizotinib (PF-02341066) is clinically effective in patients with ALK-translocated cancers, but its efficacy will ultimately be limited by acquired drug resistance. Here we report the identification of a secondary mutation in ALK, F1174L, as one cause of crizotinib resistance in a patient with an inflammatory myofibroblastic tumor (IMT) harboring a RANBP2-ALK translocation who progressed while on crizotinib therapy. When present in cis with an ALK translocation, this mutation (also detected in neuroblastomas) causes an increase in ALK phosphorylation, cell growth, and downstream signaling. Furthermore, the F1174L mutation inhibits crizotinib-mediated downregulation of ALK signaling and blocks apoptosis in RANBP2-ALK Ba/F3 cells. A chemically distinct ALK inhibitor, TAE684, and the HSP90 inhibitor 17-AAG are both effective in models harboring the F1174L ALK mutation. Our findings highlight the importance of studying drug resistance mechanisms in order to develop effective clinical treatments for patients with ALK-translocated cancers. PMID- 21030461 TI - PPO: predictor for prokaryotic operons. AB - SUMMARY: We present an operon predictor for prokaryotic operons (PPO), which can predict operons in the entire prokaryotic genome. The prediction algorithm used in PPO allows the user to select binary particle swarm optimization (BPSO), a genetic algorithm (GA) or some other methods introduced in the literature to predict operons. The operon predictor on our web server and the provided database are easy to access and use. The main features offered are: (i) selection of the prediction algorithm; (ii) adjustable parameter settings of the prediction algorithm; (iii) graphic visualization of results; (iv) integrated database queries; (v) listing of experimentally verified operons; and (vi) related tools. AVAILABILITY AND IMPLEMENTATION: PPO is freely available at http://bio.kuas.edu.tw/PPO/. PMID- 21030462 TI - SPHINX--an algorithm for taxonomic binning of metagenomic sequences. AB - MOTIVATION: Compared with composition-based binning algorithms, the binning accuracy and specificity of alignment-based binning algorithms is significantly higher. However, being alignment-based, the latter class of algorithms require enormous amount of time and computing resources for binning huge metagenomic datasets. The motivation was to develop a binning approach that can analyze metagenomic datasets as rapidly as composition-based approaches, but nevertheless has the accuracy and specificity of alignment-based algorithms. This article describes a hybrid binning approach (SPHINX) that achieves high binning efficiency by utilizing the principles of both 'composition'- and 'alignment' based binning algorithms. RESULTS: Validation results with simulated sequence datasets indicate that SPHINX is able to analyze metagenomic sequences as rapidly as composition-based algorithms. Furthermore, the binning efficiency (in terms of accuracy and specificity of assignments) of SPHINX is observed to be comparable with results obtained using alignment-based algorithms. AVAILABILITY: A web server for the SPHINX algorithm is available at http://metagenomics.atc.tcs.com/SPHINX/. PMID- 21030463 TI - FoxP3+ CD4+ T cells in systemic autoimmune diseases: the delicate balance between true regulatory T cells and effector Th-17 cells. AB - Breakdown of tolerance is a hallmark of autoimmune diseases. Over the past 10 years, there has been increased interest in the role of FoxP3(+) regulatory T cells (T(Regs)) in maintaining peripheral tolerance. Dysfunction of these cells is considered to play a major role in the development of autoimmune diseases. Besides their suppressive function, a fraction of these cells has the capacity to differentiate into IL-17-producing cells (Th-17), a phenomenon associated with autoimmune inflammation. The revealed plasticity of T(Regs), therefore, has obvious implications when designing therapeutic strategies for restoring tolerance in autoimmune diseases using T(Regs). In this review, we discuss development, classification, molecular characterization and mechanisms of suppression by T(Regs). In addition, we describe recent data on their potential conversion into Th-17 cells in human systemic autoimmune diseases. We also outline a new strategy for T(Reg)-based therapy via isolation, expansion and re infusion of highly pure FoxP3(+) T(Regs) free of contaminating effector T cells. PMID- 21030464 TI - Comment on: 'The cost of a QALY'. PMID- 21030466 TI - Is telomere length a biomarker of aging? A review. AB - Telomeres, the DNA-protein structures located at the ends of chromosomes, have been proposed to act as a biomarker of aging. In this review, the human evidence that telomere length is a biomarker of aging is evaluated. Although telomere length is implicated in cellular aging, the evidence suggesting telomere length is a biomarker of aging in humans is equivocal. More studies examining the relationships between telomere length and mortality and with measures that decline with "normal" aging in community samples are required. These studies would benefit from longitudinal measures of both telomere length and aging related parameters. PMID- 21030465 TI - Diastolic blood pressure levels and ischemic stroke incidence in older adults with white matter lesions. AB - BACKGROUND: The optimal blood pressure level to minimize the risk of ischemic stroke (IS) in older adults is undetermined. Cerebral white matter lesions (WML), prevalent in older adults, may be a marker for vulnerability to IS. We aimed at determining the relationship between diastolic blood pressure (DBP) levels and IS in the presence of WML. METHODS: The Cardiovascular Health Study population (N = 3,345, age >= 65 years, N = 3,345) was followed between 1989 and 2002 for IS incidence. Survival analysis included quintiles of DBP analyzed within WML levels controlling for age and cardiovascular disease. RESULTS: DBP had no effect on IS incidence in low WML levels but had a marginally significant J-curve relationship with IS in high WML levels: the adjusted hazard ratio for IS in the lowest (<63 mmHg) and highest (>= 80) DBP quintiles compared with the third (nadir, 69-73 mmHg) was 1.64 (95% confidence interval: 0.93-2.9) and 1.83 (95% confidence interval: 1.06-3.15), respectively. CONCLUSIONS: In older adults with low-grade WML, low DBP may not pose a risk for IS. However, in high-grade WML, IS risk may increase in DBP less than 69 mmHg but is highest more than 80 mmHg. People with high-grade WML may be at risk of IS in high and low DBP. PMID- 21030467 TI - Treatment of death in the analysis of longitudinal studies of gerontological outcomes. AB - BACKGROUND: Longitudinal studies in gerontology are characterized by termination of measurement from death. Death is related to many important gerontological outcomes, such as functional disability, and may, over time, change the composition of an older study population. For these reasons, treating death as noninformative censoring of a longitudinal outcome may result in biased estimates of regression coefficients related to that outcome. METHODS: In a longitudinal study of community-living older persons, we analytically and graphically illustrate the dependence between death and functional disability. Relative to survivors, decedents display a rapid decline of functional ability in the months preceding death. Death's strong relationship with functional disability demonstrates that death is not independent of this outcome and, hence, leads to informative censoring. We also demonstrate the "healthy survivor effect" that results from death's selection effect, with respect to functional disability, on the longitudinal makeup of an older study population. RESULTS: We briefly survey commonly used approaches for longitudinal modeling of gerontological outcomes, with special emphasis on their treatment of death. Most common methods treat death as noninformative censoring. However, joint modeling methods are described that take into account any dependency between death and a longitudinal outcome. CONCLUSIONS: In longitudinal studies of older persons, death is often related to gerontological outcomes and, therefore, cannot be safely assumed to represent noninformative censoring. Such analyzes must account for the dependence between outcomes and death as well as the changing nature of the cohort. PMID- 21030468 TI - Using propensity score modeling to minimize the influence of confounding risks related to prenatal tobacco exposure. AB - INTRODUCTION: Despite efforts to control for confounding variables using stringent sampling plans, selection bias typically exists in observational studies, resulting in unbalanced comparison groups. Ignoring selection bias can result in unreliable or misleading estimates of the causal effect. METHODS: Generalized boosted models were used to estimate propensity scores from 42 confounding variables for a sample of 361 neonates. Using emergent neonatal attention and orientation skills as an example developmental outcome, we examined the impact of tobacco exposure with and without accounting for selection bias. Weight at birth, an outcome related to tobacco exposure, also was used to examine the functionality of the propensity score approach. RESULTS: Without inclusion of propensity scores, tobacco-exposed neonates did not differ from their nonexposed peers in attention skills over the first month or in weight at birth. When the propensity score was included as a covariate, exposed infants had marginally lower attention and a slower linear change rate at 4 weeks, with greater quadratic deceleration over the first month. Similarly, exposure-related differences in birth weight emerged when propensity scores were included as a covariate. CONCLUSIONS: The propensity score method captured the selection bias intrinsic to this observational study of prenatal tobacco exposure. Selection bias obscured the deleterious impact of tobacco exposure on the development of neonatal attention. The illustrated analytic strategy offers an example to better characterize the impact of prenatal tobacco exposure on important developmental outcomes by directly modeling and statistically accounting for the selection bias from the sampling process. PMID- 21030470 TI - Effect of applying a sustained force during bonding orthodontic brackets on the adhesive layer and on shear bond strength. AB - The objective of this research was to investigate the effect of applying a sustained seating force during bonding on the adhesive layer and on shear bond strength (SBS) of orthodontic brackets. Forty human premolars divided into two groups were included in the study. Stainless steel brackets were bonded to the premolars with Transbond XT light cure adhesive and Transbond Plus Self Etch Primer (SEP). The brackets in both groups were subjected to an initial seating force of 300 g for 3 seconds, sufficient to position the bracket. The seating force was maintained throughout the 40 seconds of light curing in group 2. SBS was tested 24 hours after bracket bonding with a shear blade using an Instron testing unit at a crosshead speed of 2 mm/minute. A Student's t-test was used to compare the bond strength of the two groups and a chi-square test to compare the frequencies of the adhesive remnant index (ARI) scores. The mean SBS was significantly different between the two groups (P=0.025). The bond strength was higher (mean 8.15+/-0.89 MPa) in group 2 compared with group 1 (mean 7.39+/-1.14 MPa). There was no significant difference (P=0.440) in the ARI scores between the two groups. Applying a sustained seating force during orthodontic bracket bonding improves bond strength but does not change the distribution of the ARI scores. PMID- 21030469 TI - Correlation between bilirubin glucuronidation and estradiol-3-gluronidation in the presence of model UDP-glucuronosyltransferase 1A1 substrates/inhibitors. AB - Inhibition of UDP-glucuronosyltransferase (UGT) 1A1-catalyzed bilirubin glucuronidation by drug compounds may potentially be of clinical concern. However, in drug discovery and development settings, bilirubin is less than an ideal in vitro probe for assessing the potential of a chemical entity to inhibit bilirubin glucuronidation. In part, this is due to the propensity of bilirubin to photodegrade and to the instability of its metabolites. To this end, the utility of estradiol-3-glucuronidation as a surrogate in vitro predictor for interactions with bilirubin was evaluated. The glucuronidation kinetics of bilirubin and estradiol were carefully characterized with recombinant UGT1A1 expressed in human embryonic kidney 293 cells. Consistent with previous reports, estradiol-3 glucuronidation displayed sigmoidal kinetics, whereas bilirubin glucuronidation exhibited typical hyperbolic kinetics. The two compounds also mutually inhibited the metabolism of the other. Sixteen UGT1A1 substrates/inhibitors were evaluated as effectors of each reaction. Fourteen compounds inhibited both bilirubin and estradiol glucuronidation. However, two compounds (ethinylestradiol and daidzein) exhibited mixed effects (concentration-dependent activation and inhibition) on estradiol-3-glucuronidation, whereas bilirubin glucuronidation was inhibited by both compounds. In addition, 7-ethyl-10-hydroxycamptothecin, a substrate of UGT1A1 (reported K(m) = 24 MUM) seemed to be a weak inhibitor of bilirubin glucuronidation (IC(50) = 356.4 MUM) but a partial inhibitor of estradiol-3 glucuronidation. The IC(50) values of the inhibitors against estradiol-3 glucuronidation were strongly correlated with IC(50) values against bilirubin glucuronidation, resulting in an R(2) value of 0.9604 (activator excluded) or 0.8287 (activator included). Thus, estradiol-3-glucuronidation can serve as a good surrogate for predicting inhibition of bilirubin glucuronidation with the caveat that occasionally compounds may demonstrate activation of estradiol-3 glucuronidation. PMID- 21030471 TI - The fun culture in seniors' online communities. AB - PURPOSE OF THE STUDY: Previous research found that "fun on line" is the most dominant content in seniors' online communities. The present study aimed to further explore the fun culture in these communities and to discover its unique qualities. DESIGN AND METHODS: The study applied an online ethnography (netnography) approach, utilizing a full year's data from 6 leading seniors' online communities. The final database included about 50,000 posts. RESULTS: The majority of posts were part of online social games, including cognitive, associative, and creative games. The main subjects in all contents were sex, gender differences, aging, grandparenting, politics, faith, and alcohol. Main participatory behaviors were selective timing, using expressive style, and personalization of the online character. Although most participants were "lurkers," the active participants nurtured community norms and relationships, as reflected in the written dialogues. IMPLICATIONS: In a reality of limited alternatives for digital games that meet older adults' needs and interests, seniors found an independent system to satisfy their need for play. Seniors' online communities provided a unique form of casual leisure, whose nature varied among different groups of participants. The fun culture seemed to offer participants many desired benefits, including meaningful play, liminality and communitas, opportunity to practice and demonstrate their abilities, and means for coping with aging. Therefore, it may have positive impact on seniors' well being and successful aging. PMID- 21030472 TI - Authoritarian versus responsive communitarian bioethics. AB - A communitarian approach to bioethics adds a core value to a field that is often more concerned with considerations of individual autonomy. Some interpretations of liberalism put the needs of the patient over those of the community; authoritarian communitarianism privileges the needs of society over those of the patient. Responsive communitarianism's main starting point is that we face two conflicting core values, autonomy and the common good, and that neither should be a priori privileged and that we have principles and procedure that can be used to work out this conflict but not to eliminate it. Additionally, it favours changing behaviour mainly through the creation of norms and by drawing on informal social control rather than by coercion. PMID- 21030473 TI - The transformation of (bio)ethics expertise in a world of ethical pluralism. AB - Today, bioethics experts have an increasing role in public life. However, the question arises: what does bioethics expertise really mean? Can there be such a thing in our globalised world characterised by ethical pluralism? I will argue that bioethics as a discipline represents the transformation of ethics expertise from a hard to a soft form of it. Bioethics was born as a reaction to the growing awareness of ethical pluralism, and it denied the hard form of normative prescriptive ethics expertise (the ability to determine what is the right course of action for others), particularly in its medical ethics form. In contrast, the traditional medical ethics model, and pre-modern societies in general, believed in hard normative ethics expertise. From this followed the characteristic paternalism of traditional medical practice: if physicians were experts in moral matters as well, if they knew what the right course of action to choose was, then they had a right to benevolently force this course of action on their patients. The remnants of this doctrine, although rarely stated explicitly, still can often be seen in clinical practice. The whole bioethics movement can be seen as a radical denial of the doctrine of physician's hard expertise in moral matters. Bioethics, however, represents a type of soft ethics expertise (mainly value sensitivity). Hence follows the seeming paradox of bioethics expertise: bioethics is both a denial of ethics expertise (in its hard form) as well as a type of (soft) ethics expertise. PMID- 21030474 TI - Medicine and the Holocaust: a visit to the Nazi death camps as a means of teaching medical ethics in the Israel Defense Forces Medical Corps. AB - A novel method of teaching military medical ethics, medical ethics and military ethics in the Israel Defense Force (IDF) Medical Corps, essential topics for all military medical personnel, is discussed. Very little time is devoted to medical ethics in medical curricula, and even less to military medical ethics. Ninety five per cent of American students in eight medical schools had less than 1 h of military medical ethics teaching and few knew the basic tenets of the Geneva Convention. Medical ethics differs from military medical ethics: the former deals with the relationship between medical professional and patient, while in the latter military physicians have to balance between military necessity and their traditional priorities to their patients. The underlying principles, however, are the same in both: the right to life, autonomy, dignity and utility. The IDF maintains high moral and ethical standards. This stems from the preciousness of human life in Jewish history, tradition and religious law. Emphasis is placed on these qualities within the Israeli education system; the IDF teaches and enforces moral and ethical standards in all of its training programmes and units. One such programme is 'Witnesses in Uniform' in which the IDF takes groups of officers to visit Holocaust memorial sites and Nazi death camps. During these visits daily discussions touch on intricate medical and military ethical issues, and contemporary ethical dilemmas relevant to IDF officers during active missions. PMID- 21030475 TI - Ethical and legal acceptability of the use of neuromuscular blockers (NMBs) in connection with abstention decisions in Dutch NICUs: interviews with neonatologists. AB - BACKGROUND: In the Netherlands, using drugs to deliberately end the life of a severely defective newborn baby who is in extreme suffering can be permissible under very precise circumstances. This does not mean that all Dutch neonatologists are willing to engage in such behaviour. This paper discusses the use of neuromuscular blockers (NMBs) in connection with abstention decisions in neonatology and the boundaries between 'deliberate ending of life' and other end of-life decisions. These boundaries are of paramount importance because, of all end-of-life decisions, only 'deliberate ending of life' must be reported by the responsible doctor and exposes him to the risk of being prosecuted. METHODS: 14 Dutch neonatologists were presented with a hypothetical case of a severely asphyxiated baby who faces a long dying process after withdrawal of 'medically futile' (zinloos) life-sustaining ventilation. Doctors were asked whether it is acceptable to administer NMBs in this situation and whether such behaviour should be reported. RESULTS AND CONCLUSIONS: Doctors' responses were heterogeneous, showing that the acceptability of using NMBs in certain situations and the boundaries between end-of-life decisions are currently a subject of discussion among Dutch neonatologists. Many respondents reported feeling threatened by the potential involvement of the criminal law authorities in the system of control over 'deliberate ending of life'. PMID- 21030476 TI - Life support and euthanasia, a perspective on Shaw's new perspective. AB - It has recently been suggested by Shaw (2007) that the distinction between voluntary active euthanasia, such as giving a patient a lethal overdose with the intention of ending that patient's life, and voluntary passive euthanasia, such as removing a patient from a ventilator, is much less obvious than is commonly acknowledged in the literature. This is argued by suggesting a new perspective that more accurately reflects the moral features of end-of-life situations. The argument is simply that if we consider the body of a mentally competent patient who wants to die, a kind of 'unwarranted' life support, then the distinction collapses. We argue that all Shaw has provided is a perspective that makes the conclusion that there is little distinction between voluntary active euthanasia and voluntary passive euthanasia only seemingly more palatable. In doing so he has yet to convince us that this perspective is superior to other perspectives and thus more accurately reflects the moral features of the situations pertaining to this issue. PMID- 21030477 TI - Proton MR spectroscopy provides relevant prognostic information in high-grade astrocytomas. AB - BACKGROUND AND PURPOSE: There is a large range of survival times in patients with HGA that can only be partially explained by histologic grade and clinical aspects. This study aims to retrospectively assess the predictive value of single voxel (1)H-MRS regarding survival in HGA. MATERIALS AND METHODS: Pretreatment (1)H-MRS in 187 patients with HGA produced 180 spectra at STE (30 ms) and 182 at LTE (136 ms). Patients were dichotomized into 2 groups according to survival better or worse than the median. The spectra of the 2 groups were compared using the Mann-Whitney U test. The points on the spectrum with the most significant differences were selected for discriminating patients with good and poor prognosis. Thresholds were defined with ROC curves, and survival was analyzed by using the Kaplan-Meier method and the Cox proportional hazards model. RESULTS: Four points on the spectrum showed the most significant differences: 0.98 and 3.67 ppm at STE; and 0.98 and 1.25 ppm at LTE (P between <.001 and .011). These points were useful for stratifying 2 prognostic groups (P between <.001 and .003, Kaplan-Meier). The Cox forward stepwise model selected 3 spectroscopic variables: the intensity values of the points 3.67 ppm at STE (hazard ratio, 2.132; 95% CI, 1.504-3.023), 0.98 ppm at LTE (hazard ratio, 0.499; 95% CI, 0.339-0.736), and 1.25 ppm at LTE (hazard ratio, 0.574; 95% CI, 0.368-0.897). CONCLUSIONS: (1)H-MRS is of value in predicting the length of survival in patients with HGA and could be used to stratify prognostic groups. PMID- 21030478 TI - Imaging evaluation of intrathecal baclofen pump-catheter systems. AB - ITB pumps are widely used in the treatment of intractable spasticity for many clinical indications, including cerebral palsy and spinal cord injury. High-dose intrathecal administration places the patient at significant risk for withdrawal in the event of device malfunction, necessitating rapid and complete evaluation of the pump-catheter system. This article reviews the approach to imaging evaluation of ITB pump-catheter systems, with specific emphasis on radiography, fluoroscopy, CT, and nuclear scintigraphy. PMID- 21030479 TI - Style and content of CT and MR imaging lumbar spine reports: radiologist and clinician preferences. AB - BACKGROUND AND PURPOSE: Several studies have examined clinician preferences regarding the style of body sonography and CT reports. Our study is the first to examine clinicians' and radiologists' preferences in lumbar spine CT and MR imaging reports with respect to content and format and specific components such as management suggestions by the radiologist. MATERIALS AND METHODS: A spine report survey, which consisted of 3 case scenarios, each with 6 different reports varying in content and format, was mailed to clinicians and radiologists. Their preferences regarding content, format, and management suggestions were gathered. RESULTS: A total of 89 clinicians (49%) and 31 radiologists (53%) responded. Both clinicians and radiologists preferred reports with moderate or detailed instead of limited content (P < .01). Itemized and prose formats were equally acceptable to clinicians and radiologists. Although both groups identified moderate CT technique description as ideal, more clinicians valued the inclusion of the quality of a CT study (P < .001). Specialists preferred reports with greater detail but no recommendations, whereas family physicians preferred less detail but wanted specific management suggestions (P < .01). Neuroradiologists (75% 100%) were more likely to provide management suggestions than non neuroradiologists (23%-59%). CONCLUSIONS: Clinicians favored lumbar spine CT and MR imaging reports with detailed content in either itemized or structured prose formats, irrespective of the modality or the extent of abnormalities reported. Family physicians preferred management suggestions from the radiologists. Specialists, however, preferred a review of the radiologic findings and an opinion without specific recommendations. To optimize patient care, radiologists should be mindful of these preferences and consider tailoring their reports to their audiences. PMID- 21030480 TI - Electrophysiological correlates of processing faces of younger and older individuals. AB - The 'own-age bias' in face processing suggests that the age of a face constitutes one important factor that influences attention to and memory for faces. The present experiment investigated electrophysiological correlates of processing faces of younger and older individuals. Younger participants were presented with pictures of unfamiliar younger and older faces in the context of a gender categorization task. A comparison of event-related potentials showed that early components are sensitive to faces of different ages: (i) larger positive potential peaking at 160 ms (P200) for older than younger faces at fronto-central electrodes; (ii) larger negative potential peaking at 252 ms (N200) for younger than older faces at fronto-central electrodes; (iii) larger negative-going deflection peaking at 320 ms (N250) for younger than older faces at occipito temporal electrodes; and (iv) larger late positive potential peaking at 420 ms (LPP 420) for older than younger faces at parietal and other electrodes. We discuss similarities between the present study and a previously published study of faces of different races as suggesting involvement of comparable electrophysiological responses when differentiating between stimulus categories. PMID- 21030481 TI - Investigating the genetic basis of altruism: the role of the COMT Val158Met polymorphism. AB - Findings from twin studies yield heritability estimates of 0.50 for prosocial behaviours like empathy, cooperativeness and altruism. First molecular genetic studies underline the influence of polymorphisms located on genes coding for the receptors of the neuropeptides, oxytocin and vasopressin. However, the proportion of variance explained by these gene loci is rather low indicating that additional genetic variants must be involved. Pharmacological studies show that the dopaminergic system interacts with oxytocin and vasopressin. The present experimental study tests a dopaminergic candidate polymorphism for altruistic behaviour, the functional COMT Val158Met SNP. N = 101 healthy Caucasian subjects participated in the study. Altruism was assessed by the amount of money donated to a poor child in a developing country, after having earned money by participating in two straining computer experiments. Construct validity of the experimental data was given: the highest correlation between the amount of donations and personality was observed for cooperativeness (r = 0.32, P <= 0.001). Carriers of at least one Val allele donated about twice as much money as compared with those participants without a Val allele (P = 0.01). Cooperativeness and the Val allele of COMT additively explained 14.6% of the variance in donation behaviour. Results indicate that the Val allele representing strong catabolism of dopamine is related to altruism. PMID- 21030482 TI - Amygdala and dorsomedial prefrontal cortex responses to appearance-based and behavior-based person impressions. AB - We explored the neural correlates of learning about people when the affective value of both facial appearance and behavioral information is manipulated. Participants were presented with faces that were either rated as high or low on trustworthiness. Subsequently, we paired these faces with positive, negative, or no behavioral information. Prior to forming face-behavior associations, a cluster in the right amygdala responded more strongly to untrustworthy than to trustworthy faces. During learning, a cluster in the dorsomedial prefrontal cortex (dmPFC) responded more strongly to faces paired with behaviors than faces not paired with behaviors. We also observed that the activity in the dmPFC was correlated with behavioral learning performance assessed after scanning. Interestingly, individual differences in the initial amygdala response to face trustworthiness prior to learning modulated the relationship between dmPFC activity and learning. This finding suggests that the activity of the amygdala can affect the interaction between dmPFC activity and learning. PMID- 21030484 TI - Functional selectivity and biased receptor signaling. AB - With the emergence of information describing functional selectivity and biased agonists and antagonists has come a lack of confidence in "one size fits all" assays for detection of agonism. Seven-transmembrane receptors are pleiotropic with respect to the signaling protein to which they couple in a cell, and many conformations of the receptor can be formed; this leads to systems where ligands can stabilize unique conformations that go on to selectively activate signaling pathways. Thus, such "biased" ligands can produce cell-specific agonism that may require targeted assays to detect and quantify. It also predicts that ligands can have many different efficacies for the many behaviors that the receptor can exhibit (referred to as "pluridimensional efficacy"), leading to a breakdown in the common classifications of agonist and antagonist. This all poses unique challenges to the pharmacologic nomenclature of drugs, the detection and optimization of new drugs, and the association of phenotypic clinical profiles with pharmacological properties of drugs. PMID- 21030483 TI - Central cannabinoid receptors modulate acquisition of eyeblink conditioning. AB - Delay eyeblink conditioning is established by paired presentations of a conditioned stimulus (CS) such as a tone or light, and an unconditioned stimulus (US) that elicits the blink reflex. Conditioned stimulus information is projected from the basilar pontine nuclei to the cerebellar interpositus nucleus and cortex. The cerebellar cortex, particularly the molecular layer, contains a high density of cannabinoid receptors (CB1R). The CB1Rs are located on the axon terminals of parallel fibers, stellate cells, and basket cells where they inhibit neurotransmitter release. The present study examined the effects of a CB1R agonist WIN55,212-2 and antagonist SR141716A on the acquisition of delay eyeblink conditioning in rats. Rats were given subcutaneous administration of 1, 2, or 3 mg/kg of WIN55,212-2 or 1, 3, or 5 mg/kg of SR141716A before each day of acquisition training (10 sessions). Dose-dependent impairments in acquisition were found for WIN55,212-2 and SR141716A, with no effects on spontaneous or nonassociative blinking. However, the magnitude of impairment was greater for WIN55,212-2 than SR141716A. Dose-dependent impairments in conditioned blink response (CR) amplitude and timing were found with WIN55,212-2 but not with SR141716A. The findings support the hypothesis that CB1Rs in the cerebellar cortex play an important role in plasticity mechanisms underlying eyeblink conditioning. PMID- 21030485 TI - Cytochrome P450 2J2 is highly expressed in hematologic malignant diseases and promotes tumor cell growth. AB - Cytochrome P450 2J2 (CYP2J2) epoxygenase converts arachidonic acid to four regioisomeric epoxyeicosatrienoic acids (EETs) that exert multiple biological effects in the cardiovascular system and in various human solid cancers. However, it is unknown whether this enzyme is expressed or plays any role in malignant hematological diseases. In this study, we found strong and highly selective CYP2J2 expression in five human-derived malignant hematological cell lines and in leukemia cells from peripheral blood and bone marrow in 36 of 42 patients (86%) with malignant hematologic diseases. Furthermore, increased levels of EETs were detected in urine and blood samples from these patients. Addition of exogenous EET or CYP2J2 overexpression in cultured human-derived malignant hematologic cell lines markedly accelerated proliferation and attenuated apoptosis. Addition of the selective CYP2J2 inhibitor compound 26 (C26; 1-[4-(vinyl) phenyl]-4-[4 (diphenyl-hydroxymethyl)-piperidinyl]-butanone hydrochloride) inhibited cell proliferation and increased apoptosis, an effect that was significantly reversed by EET. CYP2J2 overexpression and exogenous EET activated AMP-activated protein kinase, c-Jun NH(2)-terminal kinase, and phosphatidylinositol 3-kinase/Akt signaling pathways, and increased epidermal growth factor receptor phosphorylation levels. CYP2J2 overexpression also enhanced malignant xenograft growth, which was efficiently inhibited by oral administration of C26 in Tie2 CYP2J2 transgenic mice and in severe combined immunodeficiency (SCID) xenograft mice. Together, these results suggest that CYP2J2 plays a key role in the pathogenesis of human hematologic malignant diseases. Selective inhibition of CYP2J2 may be a promising therapeutic strategy for these conditions. PMID- 21030486 TI - Motor learning with augmented feedback: modality-dependent behavioral and neural consequences. AB - Sensory information is critical to correct performance errors online during the execution of complex tasks and can be complemented by augmented feedback (FB). Here, 2 groups of participants acquired a new bimanual coordination pattern under different augmented FB conditions: 1) visual input reflecting coordination between the 2 hands and 2) auditory pacing integrating the timing of both hands into a single temporal structure. Behavioral findings revealed that the visual group became dependent on this augmented FB for performance, whereas the auditory group performed equally well with or without augmented FB by the end of practice. Functional magnetic resonance imaging (fMRI) results corroborated these behavioral findings: the visual group showed neural activity increases in sensory specific areas during practice, supporting increased reliance on augmented FB. Conversely, the auditory group showed a neural activity decrease, specifically in areas associated with cognitive/sensory monitoring of motor task performance, supporting the development of a control mode that was less reliant on augmented FB sources. Finally, some remnants of brain activity in sensory-specific areas in the absence of augmented FB were found for the visual group only, illustrating ongoing reliance on these areas. These findings provide the first neural account for the "guidance hypothesis of information FB," extensively supported by behavioral research. PMID- 21030487 TI - Use of videoconferencing for consultation in dental prosthetics and oral rehabilitation. AB - We conducted a 13-month study to investigate whether videoconferencing could be used for diagnosis and for making treatment plans for patients requiring prosthetic or oral rehabilitation treatment. The consultations took place between a specialist dental treatment unit in a central hospital and general dental practitioners in seven regional health centres. Videoconferencing was conducted using standard commercial units via an IP network, at bandwiths of 762 kbit/s - 2 Mbit/s. In total, 24 patients and 25 professionals (18 dentists, 2 dental hygienists and 5 nurses) took part. There were no technical problems. In 24 out of 27 teleconsultations, a diagnosis or treatment plan could be made. All participating dentists were satisfied with the consultation process and indicated that the technology used was of sufficient quality for clinical purposes. A patient satisfaction questionnaire indicated that patients were also satisfied. Videoconsultation in dentistry has the potential to increase the total number of dental specialist services in sparsely populated areas, such as those in Finland. PMID- 21030488 TI - A systematic review of the reliability of screening for cognitive impairment in older adults by use of standardised assessment tools administered via the telephone. AB - We conducted a systematic review to identify the extent to which the process of screening for cognitive impairment in older adults has been validated for administration by telephone. A search of electronic databases and a handsearch of relevant journals and reference lists were carried out for studies published between 1966 and 2008. The database search identified 411 studies and handsearching found another seven. Fourteen studies were finally identified as relevant to the review: three concerned a modified telephone version of the Mini Mental State Examination (MMSE); five concerned the Telephone Interview for Cognitive Status; one study tested a telephone-administered Short Portable Mental Status Questionnaire; four studies tested the validity of newly developed tools; and the remaining study considered the Confusion Assessment Method as a means of diagnosing delirium. The quality of the reference standard varied among the papers reviewed. The limited number of high quality studies with suitable reference standards makes it difficult to recommend a specific tool which should be used to assess the cognition of older adults by telephone. In advance of further studies, the 22-item MMSE is simple to administer and was shown to correlate well with the face-to-face MMSE. It appears to be a useful technique for telephone screening for cognitive impairment or delirium, if used in conjunction with the Delirium Symptom Interview. PMID- 21030490 TI - Accuracy of ultrasonography performed by critical care physicians for the diagnosis of DVT. AB - BACKGROUND: DVT is common among critically ill patients. A rapid and accurate diagnosis is essential for patient care. We assessed the accuracy and timeliness of intensivist-performed compression ultrasonography studies (IP-CUS) for proximal lower extremity DVT (PLEDVT) by comparing results with the formal vascular study (FVS) performed by ultrasonography technicians and interpreted by radiologists. METHODS: We conducted a multicenter, retrospective review of IP-CUS examinations performed in an ICU by pulmonary and critical care fellows and attending physicians. Patients suspected of having DVT underwent IP-CUS, using a standard two-dimensional compression ultrasonography protocol for the diagnosis of PLEDVT. The IP-CUS data were collected prospectively as part of a quality improvement initiative. The IP-CUS interpretation was recorded and timed at the end of the examination on a standardized report form. An FVS was then ordered, and the FVS result was used as the criterion standard for calculating sensitivity and specificity. Time delays between the IP-CUS and FVS were recorded. RESULTS: A total of 128 IP-CUS were compared with an FVS. Eighty-one percent of the IP-CUS were performed by fellows with <2 years of clinical ultrasonography experience. Prevalence of DVT was 20%. IP-CUS studies yielded a sensitivity of 86% and a specificity of 96% with a diagnostic accuracy of 95%. Median time delay between the ordering of FVS and the FVS result was 13.8 h. CONCLUSIONS: Rapid and accurate diagnosis of proximal lower extremity DVT can be achieved by intensivists performing compression ultrasonography at the bedside. PMID- 21030489 TI - Procalcitonin and C-reactive protein in hospitalized adult patients with community-acquired pneumonia or exacerbation of asthma or COPD. AB - BACKGROUND: Antibiotic overuse in respiratory illness is common and is associated with drug resistance and hospital-acquired infection. Biomarkers that can identify bacterial infections may reduce antibiotic prescription. We aimed to compare the usefulness of the biomarkers procalcitonin and C-reactive protein (CRP) in patients with pneumonia or exacerbations of asthma or COPD. METHODS: Patients with a diagnosis of community-acquired pneumonia or exacerbation of asthma or COPD were recruited during the winter months of 2006 to 2008. Demographics, clinical data, and blood samples were collected. Procalcitonin and CRP concentrations were measured from available sera. RESULTS: Sixty-two patients with pneumonia, 96 with asthma, and 161 with COPD were studied. Serum procalcitonin and CRP concentrations were strongly correlated (Spearman rank correlation coefficient [rs] = 0.56, P < .001). Patients with pneumonia had increased procalcitonin and CRP levels (median [interquartile range] 1.27 ng/mL [2.36], 191 mg/L [159]) compared with those with asthma (0.03 ng/mL [0.04], 9 mg/L [21]) and COPD (0.05 ng/mL [0.06], 16 mg/L [34]). The area under the receiver operating characteristic curve (95% CI) for distinguishing between patients with pneumonia (antibiotics required) and exacerbations of asthma (antibiotics not required), for procalcitonin and CRP was 0.93 (0.88-0.98) and 0.96 (0.93-1.00). A CRP value > 48 mg/L had a sensitivity of 91% (95% CI, 80% 97%) and specificity of 93% (95% CI, 86%-98%) for identifying patients with pneumonia. CONCLUSIONS: Procalcitonin and CRP levels can both independently distinguish pneumonia from exacerbations of asthma. CRP levels could be used to guide antibiotic therapy and reduce antibiotic overuse in hospitalized patients with acute respiratory illness. PMID- 21030491 TI - Rapid on-site evaluation of transbronchial aspirates in the diagnosis of hilar and mediastinal adenopathy: a randomized trial. AB - BACKGROUND: Rapid on-site evaluation (ROSE) of transbronchial needle aspirates has long been used during flexible bronchoscopy, but its usefulness in the diagnosis of hilar and mediastinal adenopathy is controversial. The aim of the present study was to evaluate the extent to which ROSE can be valuable in patients undergoing transbronchial needle aspiration (TBNA) for the diagnosis of hilar and mediastinal adenopathy. METHODS: A total of 168 consecutive patients with enlarged lymph nodes were randomized to undergo TBNA with or without ROSE. The primary outcome measure of the study was the diagnostic yield of TBNA on a per-patient basis. Secondary outcome measures included the percentage of adequate specimens on a per-lymph node basis, the number of biopsy sites on a per-patient basis, and the complication rate of bronchoscopy on a per-patient basis. RESULTS: We found no significant difference between the TBNA group and the ROSE group in terms of diagnostic yield (75.3% vs 78.3%, respectively; P = .64), and percentage of adequate specimens (86.5% vs 78.4%, respectively; P = .11). The median (interquartile range) number of biopsy sites was significantly lower in the ROSE group (1 [1-2] vs 2 [1-2], respectively; P = .0005). The complication rate of bronchoscopy was significantly lower in patients undergoing on-site review (6% vs 20%; P = .01), whereas the complication rate of TBNA was similar among the study groups. CONCLUSIONS: ROSE of transbronchial aspirates from hilar and mediastinal nodes enables avoidance of additional biopsy without loss in diagnostic yield and reduces the complication rate of bronchoscopy. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00915330; URL: www.clinicaltrials.gov PMID- 21030492 TI - The acute effects of water-pipe smoking on the cardiorespiratory system. AB - OBJECTIVE: There are limited data on the acute effects of water-pipe tobacco smoking, commonly known as water-pipe smoking (WPS), on cardiopulmonary parameters. This study evaluated the acute effects of a single 30-min session of WPS on carboxyhemoglobin (COHb) levels, pulmonary function test results, vital signs, fractional exhaled nitric oxide (Feno) levels, and exhaled breath condensate (EBC) cytokine levels in volunteers in a domestic, open-air, group smoking setting. METHODS: This prospective study evaluated the above-noted outcome parameters before and after 30 min of WPS. The primary outcome parameter was the change in COHb levels. RESULTS: Forty-five volunteers (30 men, 15 women), aged 32.35 +/- 15.33 years, were recruited. After one session of WPS, the COHb levels rose significantly, from 1.47% +/- 0.57% (median 1.4) to 9.47% +/- 5.52% (median 7.4), P < .001. Systolic and diastolic BP levels significantly increased after smoking (systolic, 119.52 +/- 12.07 mm Hg vs 131.98 +/- 17.8 mm Hg; diastolic, 74.84 +/- 7.89 mm Hg vs 82.98 +/- 12.52 mm Hg, respectively; P < .001). Heart rates increased from 80.39 +/- 9.92 beats/min to 95.59 +/- 17.41 beats/min, P < .001; and respiratory rates increased from 14.36 +/- 1.63 breaths/min to 16.68 +/- 2.24 breaths/min, P < .001. There were decreases in forced expiratory flow between 25% and 75% of FVC, peak expiratory flow rate, Feno levels, percentage of eosinophils in peripheral blood, and 8-isoprostane levels in EBC. CONCLUSIONS: This study shows that one session of WPS causes acute biologic changes that might result in marked health problems. It adds to the limited evidence that WPS is harmful and supports interventions to control the continuing global spread of WPS, especially among youth. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01157832; URL: www.clinicaltrials.gov. PMID- 21030494 TI - Pyrrolidine dithiocarbamate inhibits nuclear factor-kappaB pathway activation, and regulates adhesion, migration, invasion and apoptosis of endometriotic stromal cells. AB - The activation of nuclear factor-kappaB (NF-kappaB) has been implicated in the development and progression of endometriosis. The aim of this study is to investigate the potential application of pyrrolidine dithiocarbamate (PDTC), a potent NF-kappaB inhibitor, in the treatment of endometriosis. NF-kappaB-DNA binding activity, IkappaB phosphorylation and expression of nuclear p65 protein in endometriotic ectopic stromal cells (EcSCs), endometriotic eutopic stromal cells (EuSCs) and normal endometrial stromal cells (NESCs) were detected by electrophoretic mobility shift assay and western blot analysis. Adhesion, migration, invasion and apoptosis of EcSCs were observed by means of adhesion, migration, invasion and terminal deoxynucleotidyl transferase-mediated dUDP nick end labeling assay, respectively. Gene and protein expressions of CD44s, matrix metalloproteinase (MMP)-2, MMP-9 and survivin in EcSCs were measured by RT-PCR and western blot analysis. The results showed that PDTC in the absence or presence of interleukin (IL)-1beta showed stronger inhibitory effects on NF kappaB-DNA-binding activity, IkappaB phosphorylation and expression of nuclear p65 protein in EcSCs than those in EuSCs or NESCs. PDTC enhanced apoptosis, and suppressed IL-1beta-induced cellular adhesion, migration and invasion of EcSCs. Pretreatment of EcSCs with PDTC attenuated IL-1beta-induced expressions of CD44s, MMP-2, MMP-9 and survivin at gene and protein levels. All these findings suggest that PDTC induces apoptosis and down-regulates adhesion, migration and invasion of EcSCs through the suppression of various molecules. Therefore, PDTC could be used as a therapeutic agent for the treatment of endometriosis. PMID- 21030493 TI - Proteogenomic analysis of polymorphisms and gene annotation divergences in prokaryotes using a clustered mass spectrometry-friendly database. AB - Precise annotation of genes or open reading frames is still a difficult task that results in divergence even for data generated from the same genomic sequence. This has an impact in further proteomic studies, and also compromises the characterization of clinical isolates with many specific genetic variations that may not be represented in the selected database. We recently developed software called multistrain mass spectrometry prokaryotic database builder (MSMSpdbb) that can merge protein databases from several sources and be applied on any prokaryotic organism, in a proteomic-friendly approach. We generated a database for the Mycobacterium tuberculosis complex (using three strains of Mycobacterium bovis and five of M. tuberculosis), and analyzed data collected from two laboratory strains and two clinical isolates of M. tuberculosis. We identified 2561 proteins, of which 24 were present in M. tuberculosis H37Rv samples, but not annotated in the M. tuberculosis H37Rv genome. We were also able to identify 280 nonsynonymous single amino acid polymorphisms and confirm 367 translational start sites. As a proof of concept we applied the database to whole-genome DNA sequencing data of one of the clinical isolates, which allowed the validation of 116 predicted single amino acid polymorphisms and the annotation of 131 N terminal start sites. Moreover we identified regions not present in the original M. tuberculosis H37Rv sequence, indicating strain divergence or errors in the reference sequence. In conclusion, we demonstrated the potential of using a merged database to better characterize laboratory or clinical bacterial strains. PMID- 21030495 TI - Preterm birth does not affect bone mineral density in young adults. AB - OBJECTIVE: Previous studies showed conflicting data on the effect of prematurity on bone mineral density (BMD) in infants and children. Only a few studies investigated the long-term effects of prematurity on BMD in early adulthood. The objective of our study was to assess the long-term effects of preterm birth on BMD of the total body (BMD(TB)), lumbar spine (BMD(LS)) and bone mineral apparent density of the LS (BMAD(LS)). DESIGN: Cross-sectional study. METHODS: It consists of two hundred and seventy-six healthy subjects without serious postnatal complications, aged 18-24 years. The contribution of gestational age to the variance in BMD in young adulthood and the differences in BMD between 151 subjects born preterm (median gestational age 32.2 weeks (interquartile range (IQR) 30.3-34.0)) and 125 subjects born at term (median gestational age 40.0 weeks (IQR 39.0-40.0)) were investigated. BMD was determined by dual-energy X-ray absorptiometry. RESULTS: There were no significant linear correlations between gestational age and BMD(TB) (r=0.063, P=0.30), BMD(LS) (r=0.062, P=0.31) and BMAD(LS) (r=0.069, P=0.26). Also after adjustment for possible confounders, gestational age was no significant contributor to the variance in BMD(TB) (P=0.27), BMD(LS) (P=0.91) and BMAD(LS) (P=0.87). No significant differences were found between preterm and term subjects with regard to BMD(TB), BMD(LS) and BMAD(LS). CONCLUSION: In our cohort of 276 young adults, aged 18-24 years, gestational age was not a significant determinant in the variance of BMD. Preterm birth without serious postnatal complications is not associated with a lower BMD in young adulthood. PMID- 21030496 TI - Bevacizumab plus fotemustine as first-line treatment in metastatic melanoma patients: clinical activity and modulation of angiogenesis and lymphangiogenesis factors. AB - PURPOSE: To assess the clinical and biological activity of the association of bevacizumab and fotemustine as first-line treatment in advanced melanoma patients. EXPERIMENTAL DESIGN: Previously untreated, metastatic melanoma patients (n = 20) received bevacizumab (at 15 mg/kg every 3 weeks) and fotemustine (100 mg/m2 by intravenous administration on days 1, 8, and 15, repeated after 4 weeks) in a multicenter, single-arm, open-label, phase II study. Primary endpoint was the best overall response rate; other endpoints were toxicity, time to progression (TTP), and overall survival (OS). Serum cytokines, angiogenesis, and lymphangiogenesis factors were monitored by multiplex arrays and by in vitro angiogenesis assays. Effects of fotemustine on melanoma cells, in vitro, on vascular endothelial growth factor (VEGF)-C release and apoptosis were assessed by ELISA and flow cytometry, respectively. RESULTS: One complete response, 2 partial responses (PR), and 10 patients with stable disease were observed. TTP and OS were 8.3 and 20.5 months, respectively. Fourteen patients experienced adverse events of toxicity grade 3-4. Serum VEGF-A levels in evaluated patients (n = 15) and overall serum proangiogenic activity were significantly inhibited. A significant reduction in VEGF-C levels was found in several post-versus pretherapy serum samples. In vitro, fotemustine inhibited VEGF-C release by melanoma cells without inducing significant cell death. Serum levels of interleukin (IL)-10 and IL-12p70 showed the highest levels in sera of PR patients, compared with patients with stable or progressive disease whereas IL-23 showed the opposite pattern. CONCLUSIONS: The combination of bevacizumab plus fotemustine has clinical activity in advanced melanoma and promotes systemic modulation of angiogenesis and lymphangiogenesis factors. PMID- 21030497 TI - Highly purified eicosapentaenoic acid as free fatty acids strongly suppresses polyps in Apc(Min/+) mice. AB - PURPOSE: Although cyclooxygenase (COX)-2 inhibitors could represent the most effective chemopreventive tool against colorectal cancer (CRC), their use in clinical practice is hampered by cardiovascular side effects. Consumption of omega-3-polyunsaturated fatty acids (omega-3-PUFAs) is associated with a reduced risk of CRC. Therefore, in this study, we assessed the efficacy of a novel 99% pure preparation of omega-3-PUFA eicosapentaenoic acid as free fatty acids (EPA FFA) on polyps in Apc(Min/+) mice. EXPERIMENTAL DESIGN: Apc(Min/+) and corresponding wild-type mice were fed control diet (Ctrl) or diets containing either EPA-FFA 2.5% or 5%, for 12 weeks while monitoring food intake and body weight. RESULTS: We found that both EPA-FFA diets protected from the cachexia observed among Apc(Min/+) animals fed Ctrl diet (P < 0.0054), without toxic effect, in conjunction with a significant decrease in lipid peroxidation in the treated arms. Moreover, both EPA-FFA diets dramatically suppressed polyp number (by 71.5% and 78.6%, respectively; P < 0.0001) and load (by 82.5% and 93.4%, respectively; P < 0.0001) in both small intestine and colon. In addition, polyps less than 1 mm in size were predominantly found in the EPA-FFA 5% arm whereas those 1 to 3 mm in size were more frequent in the Ctrl arm (P < 0.0001). Interestingly, in the EPA-FFA groups, mucosal arachidonic acid was replaced by EPA (P < 0.0001), leading to a significant reduction in COX-2 expression and beta catenin nuclear translocation. Moreover, in the EPA-FFA arms, we found a significant decrease in proliferation throughout the intestine together with an increase in apoptosis. CONCLUSIONS: Our data make 99% pure EPA-FFA an excellent candidate for CRC chemoprevention. PMID- 21030498 TI - Development of central nervous system metastases in patients with advanced non small cell lung cancer and somatic EGFR mutations treated with gefitinib or erlotinib. AB - PURPOSE: Gefitinib and erlotinib can penetrate into the central nervous system (CNS) and elicit responses in patients with brain metastases (BM) from non-small cell lung cancer (NSCLC). However, there are incomplete data about their impact on the development and control of CNS metastases. EXPERIMENTAL DESIGN: Patients with stage IIIB/IV NSCLC with somatic EGFR mutations initially treated with gefitinib or erlotinib were identified. The cumulative risk of CNS progression was calculated using death as a competing risk. RESULTS: Of the 100 patients, 19 had BM at the time of diagnosis of advanced NSCLC; 17 of them received CNS therapy before initiating gefitinib or erlotinib. Eighty-four patients progressed after a median potential follow-up of 42.2 months. The median time to progression was 13.1 months. Twenty-eight patients developed CNS progression, 8 of whom had previously treated BM. The 1- and 2-year actuarial risk of CNS progression was 7% and 19%, respectively. Patient age and EGFR mutation genotype were significant predictors of the development of CNS progression. The median overall survival for the entire cohort was 33.1 months. CONCLUSIONS: Our data suggest a lower risk of CNS progression in patients with advanced NSCLC and somatic EGFR mutations initially treated with gefitinib or erlotinib than published rates of 40% in historical series of advanced NSCLC patients. Further research is needed to distinguish between the underlying rates of developing CNS metastases between NSCLC with and without EGFR mutations and the impact of gefitinib and erlotinib versus chemotherapy on CNS failure patterns in these patients. PMID- 21030500 TI - Antimicrobial resistance in group B streptococcus: the Australian experience. AB - Intrapartum chemoprophylaxis for pregnant group B streptococcus (GBS) carriers reduces vertical transmission, with a resultant decrease in neonatal as well as maternal morbidity from invasive GBS infection. Current Australian guidelines recommend penicillin for intrapartum prophylaxis of GBS carriers, with erythromycin or clindamycin for those with a beta-lactam allergy. Recent reports globally suggest that resistance to erythromycin and clindamycin may be increasing; hence, a study was undertaken to promote an evidence base for local clinical guidelines. Samples collected for standardized susceptibility testing included 1160 invasive GBS isolates (264 isolates retrospectively from 1982 to 2001 and prospectively from 2002 to 2006, plus 896 prospectively collected colonizing GBS isolates gathered over a 12 month period from 2005 to 2006) from 16 laboratories around Australia. All isolates displaying phenotypic macrolide or lincosamide resistance were subsequently genotyped. No isolates showed reduced susceptibility to penicillin or vancomycin. Of the invasive isolates, 6.4 % demonstrated phenotypic erythromycin resistance and 4.2 % were clindamycin resistant. Of the erythromycin-resistant isolates, 53 % showed cross-resistance to clindamycin. Very similar results were found in colonizing specimens. There was no statistically significant change in macrolide-resistance rates over the two study periods 1982-2001 and 2002-2006. Genotyping for macrolide and lincosamide-resistant isolates was largely consistent with phenotype. These findings suggest that penicillin therapy remains an appropriate first-line antibiotic choice for intrapartum GBS chemoprophylaxis, with erythromycin and/or clindamycin resistance being low in the Australian population. It would, nevertheless, be appropriate for laboratories screening for GBS in obstetric patients to consider macrolide sensitivity testing, particularly for those with beta-lactam allergy, to ensure appropriate chemoprophylaxis. PMID- 21030499 TI - Coffee and caffeine consumption in relation to sex hormone-binding globulin and risk of type 2 diabetes in postmenopausal women. AB - OBJECTIVE: Coffee consumption has been inversely associated with type 2 diabetes risk, but its mechanisms are largely unknown. We aimed to examine whether plasma levels of sex hormones and sex hormone-binding globulin (SHBG) may account for the inverse association between coffee consumption and type 2 diabetes risk. RESEARCH DESIGN AND METHODS: We conducted a case-control study nested in the prospective Women's Health Study (WHS). During a median follow-up of 10 years, 359 postmenopausal women with newly diagnosed type 2 diabetes were matched with 359 control subjects by age, race, duration of follow-up, and time of blood draw. RESULTS: Caffeinated coffee was positively associated with SHBG but not with sex hormones. Multivariable-adjusted geometric mean levels of SHBG were 26.6 nmol/l among women consuming >=4 cups/day of caffeinated coffee and 23.0 nmol/l among nondrinkers (P for trend = 0.01). In contrast, neither decaffeinated coffee nor tea was associated with SHBG or sex hormones. The multivariable-adjusted odds ratio (OR) of type 2 diabetes for women consuming >=4 cups/day of caffeinated coffee compared with nondrinkers was 0.47 (95% CI 0.23-0.94; P for trend = 0.047). The association was largely attenuated after further adjusting for SHBG (OR 0.71 [95% CI 0.31-1.61]; P for trend = 0.47). In addition, carriers of rs6259 minor allele and noncarriers of rs6257 minor allele of SHBG gene consuming >=2 cups/day of caffeinated coffee had lower risk of type 2 diabetes in directions corresponding to their associated SHBG. CONCLUSIONS: Our findings suggest that SHBG may account for the inverse association between coffee consumption and type 2 diabetes risk among postmenopausal women. PMID- 21030501 TI - Q fever: the neglected biothreat agent. AB - Coxiella burnetii is the causative agent of Q fever, a disease with a spectrum of presentations from the mild to fatal, including chronic sequelae. Since its discovery in 1935, it has been shown to infect a wide range of hosts, including humans. A recent outbreak in Europe reminds us that this is still a significant pathogen of concern, very transmissible and with a very low infectious dose. For these reasons it has also featured regularly on various threat lists, as it may be considered by the unscrupulous for use as a bioweapon. As an intracellular pathogen, it has remained an enigmatic organism due to the inability to culture it on laboratory media. As a result, interactions with the host have been difficult to elucidate and we still have a very limited understanding of the molecular mechanisms of virulence. However, two recent developments will open up our understanding of C. burnetii: the first axenic growth medium capable of supporting cell-free growth, and the production of the first isogenic mutant. We are approaching an exciting time for expanding our knowledge of this organism in the next few years. PMID- 21030502 TI - A case of infection caused by the basidiomycete Phellinus undulatus. AB - We present a case of soft tissue infection caused by the basidiomycete Phellinus undulatus. To our knowledge, this is the first reported case of human infection caused by this fungus. Definitive identification was only possible through molecular analysis as the isolate failed to produce any distinct morphological features in vitro. PMID- 21030503 TI - Identification of predominant culturable vaginal Lactobacillus species and associated bacteriophages from women with and without vaginal discharge syndrome in South Africa. AB - Lactobacillus jensenii, Lactobacillus crispatus, Lactobacillus iners, Lactobacillus gasseri and Lactobacillus vaginalis were identified by 16S rRNA gene sequencing as the predominant culturable vaginal Lactobacillus species in a group of South African women, comprising 24, 22, 10, 10 and 9 %, respectively. A significant effect of vaginal discharge syndrome (VDS) and bacterial vaginosis (BV) on the distribution of predominant Lactobacillus species was observed. Whilst L. crispatus isolates were almost equally distributed between individuals with and without VDS and were not significantly reduced in women with BV versus normal microflora, L. jensenii isolates were significantly reduced in women with VDS (P=0.022) and reduced in women with BV versus normal microflora (P=0.053). Unlike L. crispatus, L. jensenii isolates were also significantly reduced in women with BV-associated VDS versus women without VDS and with normal microflora (P=0.051). In addition, lysogeny was commonly observed for L. crispatus, with 77 % of isolates yielding phage particles with contractile and non-contractile tails. Only 29 % of L. jensenii isolates yielded phage particles, and these were visible as tailless or podo-like particles. PMID- 21030504 TI - Molecular typing of Staphylococcus aureus bloodstream isolates from geriatric patients attending a long-term care Spanish hospital. AB - All Staphylococcus aureus isolates (n=31) that caused bacteraemia in a Spanish geriatric hospital during 1996-2006 were analysed by a simple, rapid and inexpensive PCR technique based on variations in the hsdS1 and hsdS2 genes encoding the sequence recognition subunits of the Sau1 restriction-modification (RM) system. An equal number of isolates collected from surgical wounds over the same time period (control group) were similarly characterized. The RM test allocated 75 % of the isolates to the six major clonal complexes (CC1, CC5, CC8, CC22, CC30 and CC45) for which it was developed. However, recognition of minor CCs and precise identification of the circulating clones required more powerful and comprehensive techniques such as spa typing and multilocus sequence typing (MLST), which are more demanding and expensive. The RM test is not intended to replace spa or MLST typing, but may be of use when time, technical and/or financial resources are limited. Overall, nine and seven CCs were detected in bloodstream and wound isolates, respectively. In both groups, CC5 was the most frequent (35.5 % each), followed by CC45 or CC8 (22.6 and 32.3 % of bloodstream and wound isolates, respectively). The frequency of meticillin resistance was lower in bloodstream (16.1 %) than in wound (51.6 %) isolates (P=0.0025). Among the former, sequence type (ST) 5-staphylococcal cassette chromosome mec (SCCmec) II, ST5-SCCmec IV, ST45-SCCmec IV and ST125-SCCmec IV (now dominant in Spanish hospitals) clones were found. Among the wound isolates, nine meticillin-resistant clones were represented, with three of them (ST125-SCCmec III, ST125-SCCmec V and ST14-SCCmec V) being newly described. PMID- 21030505 TI - Expression of StMYB1R-1, a novel potato single MYB-like domain transcription factor, increases drought tolerance. AB - Potato (Solanum tuberosum) is relatively vulnerable to abiotic stress conditions such as drought, but the tolerance mechanisms for such stresses in potato are largely unknown. To identify stress-related factors in potato, we previously carried out a genetic screen of potato plants exposed to abiotic environmental stress conditions using reverse northern-blot analysis. A cDNA encoding a putative R1-type MYB-like transcription factor (StMYB1R-1) was identified as a putative stress-response gene. Here, the transcript levels of StMYB1R-1 were enhanced in response to several environmental stresses in addition to drought but were unaffected by biotic stresses. The results of intracellular targeting and quadruple 9-mer protein-binding microarray analysis indicated that StMYB1R-1 localizes to the nucleus and binds to the DNA sequence (G)/(A)GATAA. Overexpression of a StMYB1R-1 transgene in potato plants improved plant tolerance to drought stress while having no significant effects on other agricultural traits. Transgenic plants exhibited reduced rates of water loss and more rapid stomatal closing than wild-type plants under drought stress conditions. In addition, overexpression of StMYB1R-1 enhanced the expression of drought regulated genes such as AtHB-7, RD28, ALDH22a1, and ERD1-like. Thus, the expression of StMYB1R-1 in potato enhanced drought tolerance via regulation of water loss. These results indicated that StMYB1R-1 functions as a transcription factor involved in the activation of drought-related genes. PMID- 21030506 TI - Short-Root regulates primary, lateral, and adventitious root development in Arabidopsis. AB - Short-Root (SHR) is a well-characterized regulator of radial patterning and indeterminacy of the Arabidopsis (Arabidopsis thaliana) primary root. However, its role during the elaboration of root system architecture remains unclear. We report that the indeterminate wild-type Arabidopsis root system was transformed into a determinate root system in the shr mutant when growing in soil or agar. The root growth behavior of the shr mutant results from its primary root apical meristem failing to initiate cell division following germination. The inability of shr to reactivate mitotic activity in the root apical meristem is associated with the progressive reduction in the abundance of auxin efflux carriers, PIN FORMED1 (PIN1), PIN2, PIN3, PIN4, and PIN7. The loss of primary root growth in shr is compensated by the activation of anchor root primordia, whose tissues are radially patterned like the wild type. However, SHR function is not restricted to the primary root but is also required for the initiation and patterning of lateral root primordia. In addition, SHR is necessary to maintain the indeterminate growth of lateral and anchor roots. We conclude that SHR regulates a wide array of Arabidopsis root-related developmental processes. PMID- 21030507 TI - Low oleic acid-derived repression of jasmonic acid-inducible defense responses requires the WRKY50 and WRKY51 proteins. AB - Signaling induced upon a reduction in oleic acid (18:1) levels simultaneously up regulates salicylic acid (SA)-mediated responses and inhibits jasmonic acid (JA) inducible defenses, resulting in enhanced resistance to biotrophs but increased susceptibility to necrotrophs. SA and the signaling component Enhanced Disease Susceptibility1 function redundantly in this low-18:1-derived pathway to induce SA signaling but do not function in the repression of JA responses. We show that repression of JA-mediated signaling under low-18:1 conditions is mediated via the WRKY50 and WRKY51 proteins. Knockout mutations in WRKY50 and WRKY51 lowered SA levels but did not restore pathogenesis-related gene expression or pathogen resistance to basal levels in the low-18:1-containing Arabidopsis (Arabidopsis thaliana) mutant, suppressor of SA insensitivity2 (ssi2). In contrast, both JA inducible PDF1.2 (defensin) expression and basal resistance to Botrytis cinerea were restored. Simultaneous mutations in both WRKY genes (ssi2 wrky50 wrky51) did not further enhance the JA or Botrytis-related responses. The ssi2 wrky50 and ssi2 wrky51 plants contained high levels of reactive oxygen species and exhibited enhanced cell death, the same as ssi2 plants. This suggested that high reactive oxygen species levels or increased cell death were not responsible for the enhanced susceptibility of ssi2 plants to B. cinerea. Exogenous SA inhibited JA inducible PDF1.2 expression in the wild type but not in wrky50 or wrky51 mutant plants. These results show that the WRKY50 and WRKY51 proteins mediate both SA- and low-18:1-dependent repression of JA signaling. PMID- 21030508 TI - Reverse-genetic analysis of the two biotin-containing subunit genes of the heteromeric acetyl-coenzyme A carboxylase in Arabidopsis indicates a unidirectional functional redundancy. AB - The heteromeric acetyl-coenzyme A carboxylase catalyzes the first and committed reaction of de novo fatty acid biosynthesis in plastids. This enzyme is composed of four subunits: biotin carboxyl-carrier protein (BCCP), biotin carboxylase, alpha-carboxyltransferase, and beta-carboxyltransferase. With the exception of BCCP, single-copy genes encode these subunits in Arabidopsis (Arabidopsis thaliana). Reverse-genetic approaches were used to individually investigate the physiological significance of the two paralogous BCCP-coding genes, CAC1A (At5g16390, codes for BCCP1) and CAC1B (At5g15530, codes for BCCP2). Transfer DNA insertional alleles that completely eliminate the accumulation of BCCP2 have no perceptible effect on plant growth, development, and fatty acid accumulation. In contrast, transfer DNA insertional null allele of the CAC1A gene is embryo lethal and deleteriously affects pollen development and germination. During seed development the effect of the cac1a null allele first becomes apparent at 3-d after flowering, when the synchronous development of the endosperm and embryo is disrupted. Characterization of CAC1A antisense plants showed that reducing BCCP1 accumulation to 35% of wild-type levels, decreases fatty acid accumulation and severely affects normal vegetative plant growth. Detailed expression analysis by a suite of approaches including in situ RNA hybridization, promoter:reporter transgene expression, and quantitative western blotting reveal that the expression of CAC1B is limited to a subset of the CAC1A-expressing tissues, and CAC1B expression levels are only about one-fifth of CAC1A expression levels. Therefore, a likely explanation for the observed unidirectional redundancy between these two paralogous genes is that whereas the BCCP1 protein can compensate for the lack of BCCP2, the absence of BCCP1 cannot be tolerated as BCCP2 levels are not sufficient to support heteromeric acetyl-coenzyme A carboxylase activity at a level that is required for normal growth and development. PMID- 21030510 TI - Twenty-five years of airway research: personal thoughts. AB - The airway research presented for 25 years annually at the Transatlantic Airway Conferences is impressive! The imaginative Conference design, the quality of speakers, and the generosity of the sponsor are outstanding. The breadth of the Conferences is too broad for an objective review here. Instead, I offer some subjective thoughts by one who has observed the evolution of modern pulmonology. Pulmonology came late as a specialty. The National Institutes of Health deserves credit for recognizing the increasing importance of lung disease through its funded grants and changing the designation to the Heart and Lung Institute. The combined effect of enthusiastic young investigators and an increasing commitment from what was to become the National Heart, Lung, and Blood Institute provided us pulmonologists with a jump start. Here, I note the importance of the emergence of modern biology in shaping evolving airway research, and our special opportunities because of accessible anatomic features of airways. My presentation of opportunities here in immunology and in signaling may be the result of individual prejudice! Cystic fibrosis was chosen for discussion because of the importance of cloning the cystic fibrosis transmembrane regulator gene and the limited novel therapies thus far, with a plea for new ideas. The gene was (brilliantly) cloned 2 decades ago, but insights that give rise to novel life-saving therapies are still lacking. I finish with accolades to those who seek to learn from a variety of sources, including artists; I am proud and grateful that I became an early convert from cardiology to pulmonology. It continues to be an exciting experience. PMID- 21030511 TI - 25th anniversary Transatlantic Airway Conference: Protein misfolding and obstructive lung disease. PMID- 21030509 TI - Role of AtPolzeta, AtRev1, and AtPoleta in UV light-induced mutagenesis in Arabidopsis. AB - Translesion synthesis (TLS) is a DNA damage tolerance mechanism in which DNA lesions are bypassed by specific polymerases. To investigate the role of TLS activities in ultraviolet light-induced somatic mutations, we analyzed Arabidopsis (Arabidopsis thaliana) disruptants of AtREV3, AtREV1, and/or AtPOLH genes that encode TLS-type polymerases. The mutation frequency in rev3-1 or rev1 1 mutants decreased compared with that in the wild type, suggesting that AtPolzeta and AtRev1 perform mutagenic bypass events, whereas the mutation frequency in the polh-1 mutant increased, suggesting that AtPoleta performs nonmutagenic bypass events with respect to ultraviolet light-induced lesions. The rev3-1 rev1-1 double mutant showed almost the same mutation frequency as the rev1 1 single mutant. The increased mutation frequency found in polh-1 was completely suppressed in the rev3-1 polh-1 double mutant, indicating that AtPolzeta is responsible for the increased mutations found in polh-1. In summary, these results suggest that AtPolzeta and AtRev1 are involved in the same (error-prone) TLS pathway that is independent from the other (error-free) TLS pathway mediated by AtPoleta. PMID- 21030512 TI - Protein misfolding and obstructive lung disease. AB - The endoplasmic reticulum has evolved a number of mechanisms to manage the accumulation of incorrectly folded proteins. This results in loss of function of these proteins, but occasionally, in conditions such as alpha-1 antitrpysin (A1AT) deficiency, the misfolded protein can acquire a toxic gain of function promoting exaggerated ER stress responses and inflammation. Mutations leading to deficiency in a second serine proteinase inhibitor, alpha-1 antichymotrpysin (ACT), can induce potentially similar consequences. A1AT and ACT deficiencies are associated with chronic obstructive lung disease. Until recently, it was thought that the lung diseases associated with these conditions were entirely due to loss of antiprotease protection in the lung (i.e., loss of function), whereas gain of function was the major cause of the liver disease associated with A1AT deficiency. This paradigm is being increasingly challenged because ER stress is being recognized in bronchial epithelial cells and inflammatory cells normally resident in the lung, giving rise to an inflammatory phenotype that adds to the proteolytic burden associated with these conditions. In this article, we describe the cellular mechanisms that are activated to cope with an increasing burden of misfolded proteins within the ER in A1AT and ACT deficiency, show how these events are linked to inflammation, and outline the therapeutic strategies that can potentially interfere with production of misfolded proteins. PMID- 21030513 TI - The unfolded protein response in lung disease. AB - The early steps in the biogenesis of secreted and membrane proteins occur in the lumen of the endoplasmic reticulum (ER), where resident proteins that make up the ER machinery assist in their folding, maturation, and complex assembly. Variation in the load of ER client proteins and in the function of the organelle's aforementioned machinery for coping with that load can lead to an imbalance between the two that is referred to as ER stress. This triggers a cellular response, mediated by highly conserved signaling pathways that collectively restore equilibrium to the protein-folding environment in the organelle by increasing the expression of genes that enhance nearly all aspects of ER function, and by transiently repressing the biosynthesis of new client proteins. Evidence accrued over the past 10 years suggests that ER stress and response to it influence the fate of mutant proteins that fold inefficiently, impact on the functionality of cells and tissues that cope with unusual loads of ER client proteins, and intersect with signaling pathways that influence inflammation and cancer biology. Here, we review some of the basic workings of unfolded protein response and relate them to processes that are of potential relevance to pulmonary disease. PMID- 21030514 TI - Mechanisms underlying the cellular clearance of antitrypsin Z: lessons from yeast expression systems. AB - The most frequent cause of alpha(1)-antitrypsin (here referred to as AT) deficiency is homozygosity for the AT-Z allele, which encodes AT-Z. Such individuals are at increased risk for liver disease due to the accumulation of aggregation-prone AT-Z in the endoplasmic reticulum of hepatocytes. However, the penetrance and severity of liver dysfunction in AT deficiency is variable, indicating that unknown genetic and environmental factors contribute to its occurrence. There is evidence that the rate of AT-Z degradation may be one such contributing factor. Through the use of several AT-Z model systems, it is now becoming appreciated that AT-Z can be degraded through at least two independent pathways. One model system that has contributed significantly to our understanding of the AT-Z disposal pathway is the yeast, Saccharomyces cerevisiae. PMID- 21030515 TI - Cellular response to cigarette smoke and oxidants: adapting to survive. AB - The gaseous and soluble phases of cigarette smoke are sources of oxidants that contribute to the pathogenesis of chronic obstructive pulmonary disease (COPD). Chronic oxidative stress of cigarette smoking induces mucus secretion and inhibits cystic fibrosis transmembrane conductance regulator function. The increased mucus viscosity renders the airways susceptible to bacterial infections, a hallmark of chronic bronchitis. Furthermore, lungs chronically exposed to the toxic mixture of oxidants in cigarette smoke show signs of endoplasmic reticulum stress, unfolded protein response, altered ceramide metabolism, and apoptosis. Fortunately, the respiratory tract has developed effective adaptive cellular mechanisms to limit oxidant damage. Numerous antioxidant enzymes and glutathione-dependent detoxification systems are increased in healthy smokers. The regulation of the antioxidant response is largely dependent on the nuclear factor erythroid 2-related factor-2 (Nrf2) pathway. However, patients with COPD have defective Nrf2 responses. Novel therapies such as 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO) to correct defective Nrf2-dependent cellular response may hold promise for patients with COPD. PMID- 21030516 TI - Intracellular processing of alpha1-antitrypsin. AB - alpha(1)-Antitrypsin (AAT) secreted from hepatocytes is an inhibitor of neutrophil elastase. Its normal circulating concentration functions to maintain the elasticity of the lung by preventing the hydrolytic destruction of elastin fibers. Severely diminished circulating concentrations of AAT, resulting from the impaired secretion of genetic variants that exhibit distinct polypeptide folding defects, can function as an etiologic agent for the development of chronic obstructive pulmonary disease. In addition, the inappropriate accumulation of structurally aberrant AAT within the hepatocyte endoplasmic reticulum can contribute to the etiology of liver disease. This article focuses on the discovery and characterization of a biosynthetic quality control system that contributes to the secretion of AAT by first facilitating its proper structural maturation, and then by orchestrating the selective elimination of those molecules that fail to attain structural maturation. Mechanistic elucidation of these interconnected quality control events recently led to the identification of an underlying genetic modifier capable of accelerating the onset of end-stage liver disease by impairing the efficiency of an initial step in the protein disposal process. PMID- 21030517 TI - Lung disease associated with alpha1-antitrypsin deficiency. AB - alpha(1)-Antitrypsin (A1AT) is a polyvalent, acute-phase reactant with an extensive range of biological functions that go beyond those usually linked to its antiprotease (serpin) activities. Genetic mutations cause a systemic deficiency of A1AT, leading to liver and pulmonary diseases, including emphysema and chronic bronchitis. The pathogenesis of emphysema, which involves the destruction of small airway structures and alveolar units, is triggered by cigarette smoke and pollutants. The tissue damage caused by these agents is further potentiated by the mutual interactions between apoptosis, oxidative stress, and protease/antiprotease imbalance. These processes lead to the activation of endogenous mediators of tissue destruction, including the lipid ceramide, extracellular matrix proteins, and abnormal inflammatory cell signaling. In this review, we propose that A1AT has a range of actions that are not restricted to protease inhibition but rather extend to mitigate a range of these pathological processes involved in the development of emphysema. We discuss the evidence indicating that A1AT blocks apoptosis by binding and inhibiting active caspase-3 and modulates a broad range of inflammatory responses induced by neutrophils and by lipopolysaccharide and tumor necrosis factor-alpha signaling. PMID- 21030519 TI - Bone morphogenetic protein type II receptor mutations causing protein misfolding in heritable pulmonary arterial hypertension. AB - More than 70% of cases of heritable pulmonary arterial hypertension are due to heterozygous germline mutations in the gene encoding the bone morphogenetic protein type II receptor (BMPR-II), a receptor for the transforming growth factor beta/BMP superfamily. Among the many mutations identified, some involve substitution of cysteine residues in the ligand-binding domain or the kinase domains of BMPR-II. These mutants are characterized by retention within the endoplasmic reticulum. This retention causes loss of function in terms of phosphorylation of downstream Smad1, Smad5, and Smad8 and the transcription of BMP target genes. The retention has a dominant negative effect on BMP signaling because it also impairs trafficking of the associated type I receptor. Studies suggest a more severe phenotype in patients with this class of mutation. We have shown that trafficking of cysteine-substituted mutants can be partially restored in the presence of chemical chaperones. Restoration of cell surface expression of ligand-binding domain mutants leads to partial rescue of BMP signaling and suggests that small-molecule pharmacological chaperones may be a therapeutic option in these patients. PMID- 21030518 TI - Role of endoplasmic reticulum stress in cystic fibrosis-related airway inflammatory responses. AB - Chronic airway infection and inflammation are hallmarks of cystic fibrosis (CF) pulmonary disease. The altered airway environment resulting from infection and inflammation can affect the innate defense of the airway epithelia. Luminal bacterial and inflammatory stimuli trigger an adaptation in human airway epithelia, characterized by a hyperinflammatory response to inflammatory mediators, which is mediated by an expansion of the endoplasmic reticulum (ER) and its Ca(2+) stores. Recent studies demonstrated that a form of ER stress, the unfolded protein response (UPR), is activated in airway epithelia by bacterial infection-induced airway inflammation. UPR-dependent signaling is responsible for the ER Ca(2+) store expansion-mediated amplification of airway inflammatory responses. These studies highlight the functional importance of the UPR in airway inflammation and suggest that targeting the UPR may be a therapeutic strategy for airway diseases typified by chronic inflammation. This article reviews the contribution of airway epithelia to airway inflammatory responses, discusses how expansion of the ER Ca(2+) stores in inflamed airway epithelia contributes to airway inflammation, describes the functional role of the UPR in these processes, and discusses how UPR activation might be relevant for CF airways inflammatory disease. PMID- 21030520 TI - Small molecules to treat cystic fibrosis. AB - In the 21 years since the discovery of the gene that causes cystic fibrosis, our knowledge of how mutations in this gene cause the varied pathophysiological manifestations of this disease has increased substantially. This knowledge has led to the possibility of new therapeutic approaches aimed at the basic defect. This article summarizes our current knowledge of mutation-specific therapy, and focuses on orally bioavailable potentiators and correctors and suppressors of premature termination codons, including preclinical model systems and clinical trials in cystic fibrosis. PMID- 21030521 TI - The folding pathway of alpha1-antitrypsin: avoiding the unavoidable. AB - Understanding the folding pathway of alpha(1)-antitrypsin is of interest from both biomedical and fundamental molecular biology perspectives. The native fold of alpha(1)-antitrypsin is metastable, and therefore does not represent the most stable conformation that its primary sequence can adopt. More stable conformations are formed when the reactive center loop inserts, as the fourth strand, into the A beta sheet. The accessibility of these alternative low-energy folds renders alpha(1)-antitrypsin susceptible to mutations that can result in dysfunction and pathology. Here, I review some of the literature from the past 20 years, which has examined how alpha(1)-antitrypsin folds and preserves its native metastable state. In addition, I look at the relationship between alpha(1) antitrypsin folding and misfolding, and its role in disease. PMID- 21030522 TI - Gene therapy for cystic fibrosis. AB - The report of the first patients with cystic fibrosis (CF) to receive cystic fibrosis transmembrane conductance regulator gene (CFTR) therapy appeared in 1993, and since then there have been more than 20 clinical trials of both viral and nonviral gene transfer agents. These have largely been single dose to either nose or lower airway and have been designed around molecular or bioelectrical outcome measures. Both transgene mRNA and partial correction of chloride secretion have been reported, although sodium hyperabsorption has not been improved. The U.K. Cystic Fibrosis Gene Therapy Consortium is focused on a clinical program to establish whether these proof-of-principle measures translate into clinical benefit. Here, we review the published literature, discuss the limitations to gene therapy in the CF airway, and consider issues influencing the design of clinical trial programs. PMID- 21030523 TI - Proteostasis strategies for restoring alpha1-antitrypsin deficiency. AB - The function of the human proteome is defined by the proteostasis network (PN) (Science 2008;319:916; Science 2010;329:766), a biological system that generates, protects, and, where necessary, degrades a protein to optimize the cell, tissue, and organismal response to diet, stress, and aging. Numerous human diseases result from the failure of proteins to fold properly in response to mutation, disrupting the proteome. In the case of the exocytic pathway, this includes proteostasis components that direct folding, and export of proteins from the endoplasmic reticulum (ER). Included here are serpin deficiencies, a class of related diseases that result in a significant reduction of secretion of serine proteinase inhibitors from the liver into serum. In response to misfolding, variants of the serine protease alpha(1)-antitrypsin (alpha1AT) fail to exit the ER and are targeted for either ER-associated degradation or autophagic pathways. The challenge for developing alpha1AT deficiency therapeutics is to understand the PN pathways involved in folding and export. Herein, we review the role of the PN in managing the protein fold and function during synthesis in the ER and trafficking to the cell surface or extracellular space. We highlight the role of the proteostasis boundary to define the operation of the proteome (Annu Rev Biochem 2009;78:959). We discuss how manipulation of folding energetics or the PN by pharmacological intervention could provide multiple routes for restoration of variant alpha1AT function to the benefit of human health. PMID- 21030524 TI - Management of acute severe ulcerative colitis. AB - Acute severe ulcerative colitis is a potentially lethal condition that requires a pro-active approach with either effective medical treatment or timely colectomy. Although intravenous corticosteroids remain the first line treatment, in patients not responding after 3-5 days rescue medical therapy with either intravenous (IV) cyclosporine 2 mg/kg or infliximab 5 mg/kg IV should be considered. Controlled evidence supports the use of both treatments but medical rescue therapy should not defer the decision for colectomy in patients with inadequate response. Providing clear guidance for the choice between both agents is impossible due to the lack of comparative trials. The better short-term safety profile and the option for maintenance treatment favour infliximab specifically in patients already exposed to immunosuppressives. The rapid onset of action and the short half-life are advantages of cyclosporine in patients with imminent risk of colectomy. Even if cyclosporine and probably also infliximab only postpone colectomy in at least half of the patients, elective colectomy in a later stage of the disease may offer better outcomes. Whereas prolonged exposure to steroids predisposes to an increased rate of peri-operative complications it is still debated whether cyclosporine or infliximab increase peri-operative morbidity in ulcerative colitis. PMID- 21030525 TI - Not every cell is as it seems: a role for ductular epithelial cells in fibrosis? PMID- 21030526 TI - Human visceral afferent recordings: preliminary report. AB - BACKGROUND: Conditions characterised by chronic visceral pain represent a significant healthcare burden with limited treatment options. While animal models have provided insights into potential mechanisms of visceral nociception and identified candidate drug targets, these have not translated into successful treatments in humans. OBJECTIVE: To develop an in vitro afferent nerve preparation using surgically excised freshly isolated human colon and vermiform appendix-mesentery tissues. METHODS: Non-inflamed appendix (n=18) and colon (n=9) were collected from patients undergoing right and left hemicolectomy. Electrophysiological recordings were made from mesenteric nerves and the tissue stimulated chemically and mechanically. RESULTS: Ongoing neuronal activity was sparse and where units occurred peak firing rates were: colon (2.0+/-0.4 spikes/s, n=4) and appendix (2.4+/-0.6 spikes/s, n=9). Afferent nerves innervating the appendix responded with a significant increase in activity following stimulation with inflammatory mediators (73+/-10.6 vs 3.0+/-0.3 spikes/s, n=6, p<0.001, inflammatory mediator vs baseline) and capsaicin (63+/ 15.8 vs 2+/-0.3 spikes/s, n=3, p<0.001, capsaicin vs buffer). Afferent nerves innervating the colon responded with increased activity to blunt probing of the serosal surface. CONCLUSIONS: This first-in-human study demonstrates afferent nerve recordings from human gut tissue ex vivo and shows that tissue may be stimulated both chemically and mechanically to study neuronal responses. Collectively, the results provide preliminary evidence to validate this in vitro human tissue model as one that may aid future disease mechanistic studies and candidate drug testing. PMID- 21030527 TI - Sensitive multiplex detection of KRAS codons 12 and 13 mutations in paraffin embedded tissue specimens. AB - BACKGROUND: Colorectal cancer patients harbouring KRAS mutations in codon 12 or 13 do not benefit from current anti-epidermal growth factor receptor (EGFR) monoclonal antibody therapies. Efficient and robust methods are therefore required for routine clinical testing of KRAS mutation status. AIMS: To evaluate a novel multiplex assay for the rapid detection of common KRAS mutations in formalin-fixed paraffin-embedded (FFPE) tissues. METHODS: Genomic DNA was amplified by multiplex PCR using primers targeting the KRAS codon 12/13 region and an internal control gene. PCR products were hybridised on a liquid bead array containing target-specific probes and detected by particle flow cytometry. RESULTS: Analytical performance assessed with plasmid DNA and genomic DNA extracted from cell lines or model FFPE cell line dilutions showed specific detection of seven distinct KRAS mutations with a limit of detection equivalent to 1% tumour. The assay was evaluated at two independent sites with a total of 140 clinical specimens. At site 1, about 45% of the specimens from a set of 86 archived FFPE blocks with unknown KRAS mutation status were found positive for a KRAS mutation. At site 2, each of the seven mutations was detected in at least five independent specimens from a selected set of 54 residual genomic DNAs previously tested with an ARMS/Scorpion laboratory-developed test. CONCLUSIONS: This novel single-well assay is a sensitive tool compatible with the clinical laboratory workflow for the rapid assessment of KRAS mutations in solid tumour specimens. Its performance and multiplex format warrant the development of broader panels including other relevant mutations in the EGFR pathway. PMID- 21030528 TI - Detection of clonality in follicular lymphoma using formalin-fixed, paraffin embedded tissue samples and BIOMED-2 immunoglobulin primers. AB - AIMS: The BIOMED-2 multiplex PCR protocol is a commonly used procedure for assessing B cell clonality in lymphoma diagnostics. Follicular lymphoma poses a special challenge for PCR-based analyses because of high prevalence of somatic hypermutations in the rearranged immunoglobulin (IG) domains. This study aimed to evaluate the BIOMED-2 protocol performance in detection of B cell clonality in follicular lymphoma using formalin-fixed, paraffin-embedded (FFPE) tissue. METHODS: FFPE samples from 118 patients diagnosed with follicular lymphoma in the period 1998-2008 were used in the study. Clonality of IG heavy (IGH) and light chains (IGK, IGL) was assessed using a PCR procedure that was optimised for FFPE tissue. RESULTS: The highest clonal detection rates were 67.8% with the IGH Vn FR2-Jn assay and 66.1% with the IGK Vkappa-Jkappa assay. Clonality was detected in 94.9% of all FFPE follicular lymphoma samples when all assays were combined. FFPE samples stored for 1-5 years did not perform significantly differently from those stored for 6-11 years. Interobserver agreement of clonality was tested for all analyses. The lowest score (Cohen's kappa value = 0.56) was observed for the IGK Vkappa-Jkappa clonality assay. CONCLUSIONS: An improved PCR protocol for detection of clonality in FFPE samples using BIOMED-2 IG primers is presented. For best performance, a combination of IGH and IGK analyses is recommended. PMID- 21030529 TI - A randomised controlled trial of proactive telephone counselling on cold-called smokers' cessation rates. AB - OBJECTIVES: Active telephone recruitment ('cold calling') can enroll almost 45 times more smokers to cessation services than media. However, the effectiveness of proactive telephone counselling with cold-called smokers from the broader community is unknown. This study examined whether proactive telephone counselling improved abstinence, quit attempts and reduced cigarette consumption among cold called smokers. METHODS: From 48,014 randomly selected electronic telephone directory numbers, 3008 eligible smokers were identified and 1562 (51.9%) smokers recruited into the randomised controlled trial. Of these, 769 smokers were randomly allocated to proactive telephone counselling and 793 to the control (ie, mailed self-help) conditions. Six counselling calls were offered to intervention smokers willing to quit within a month and four to those not ready to quit. The 4 month, 7-month and 13-month follow-up interviews were completed by 1369 (87.6%), 1278 (81.8%) and 1245 (79.9%) participants, respectively. RESULTS: Proactive telephone counselling participants were significantly more likely than controls to achieve 7-day point prevalence abstinence at 4 months (13.8% vs 9.6%, p=0.005) and 7 months (14.3% vs 11.0%, p=0.02) but not at 13 months. There was a significant impact of telephone counselling on prolonged abstinence at 4 months (3.4% vs 1.8%, p=0.02) and at 7 months (2.2% vs 0.9%, p=0.02). At 4 months post recruitment, telephone counselling participants were significantly more likely than controls to have made a quit attempt (48.6% vs 42.9%, p=0.01) and reduced cigarette consumption (16.9% vs 9.0%, p=0.0002). CONCLUSIONS: Proactive telephone counselling initially increased abstinence and quitting behaviours among cold called smokers. Given its superior reach, quitlines should consider active telephone recruitment, provided relapse can be reduced. TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry; ACTRN012606000221550. PMID- 21030534 TI - Molecular MRI of murine atherosclerotic plaque targeting NGAL: a protein associated with unstable human plaque characteristics. AB - AIMS: Neutrophil gelatinase-associated lipocalin (NGAL) is an effector molecule of the innate immune system. One of its actions is the prolongation of matrix metalloproteinase-9 (MMP-9) activity by the formation of a degradation-resistant NGAL/MMP-9 complex. We studied NGAL in human atherosclerotic lesions and we examined whether NGAL could act as a target for molecular imaging of atherosclerotic plaques. METHODS AND RESULTS: Increased levels of NGAL and the NGAL/MMP-9 complex were associated with high lipid content, high number of macrophages, high interleukin-6 (IL-6) and IL-8 levels, and low smooth muscle cell content in human atherosclerotic lesions obtained during carotid endarterectomy (n= 122). Moreover, plaque levels of NGAL tended to be higher when intra-plaque haemorrhage (IPH) or luminal thrombus was present (n= 77) than without the presence of IPH or thrombus (n= 30). MMP-9 and -8 activities were strongly related to NGAL levels. The enhancement on magnetic resonance (MR) images of the abdominal aorta of ApoE(-/-)/eNOS(-/-) mice was observed at 72 h after injection of NGAL/24p3-targeted micelles. The specificity of these results was validated by histology, and co-localization of micelles, macrophages, and NGAL/24p3 was observed. CONCLUSION: NGAL is highly expressed in atheromatous human plaques and associated with increased MMP-9 activity. NGAL can be detected in murine atherosclerotic arteries using targeted high-resolution MR imaging. Therefore, we conclude that NGAL might serve as a novel imaging target for the detection of high-risk plaques. PMID- 21030533 TI - Improving outcomes for patients with diffuse large B-cell lymphoma. AB - Diffuse large B-cell lymphoma (DLBCL) is the most commonly occurring form of non Hodgkin lymphoma in the western world. Until the mid 1990s the incidence of DLBCL increased in both sexes, across racial categories, and across all age groups except the very young, the etiology of most cases remains unknown. DLBCL is associated with an aggressive natural history, but it can be cured with combination chemotherapy regimens like cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), which has been the mainstay of therapy for several decades. Remarkable progress has been made in understanding the biological heterogeneity of DLBCL and in improving survival for DLBCL patients with novel combinations of chemotherapy and immunotherapy. Gene expression profiling (GEP) has uncovered DLBCL subtypes that have distinct clinical behaviors and prognoses, and the addition of the monoclonal antibody, rituximab, to CHOP has markedly improved outcomes. Future approaches to DLBCL management will use molecular signatures identified through GEP to provide prognostic information and to isolate therapeutic targets that are being evaluated for DLBCL patients who relapse or those with high risk disease. PMID- 21030535 TI - The role of pulsatile flow in controlling microvascular retinal endothelial and pericyte cell apoptosis and proliferation. AB - AIMS: Aberrant retinal blood flow is a hallmark of various retinopathies and may be a causative factor in the pathology associated with these conditions. We examined the effects of pulsatile flow on bovine retinal endothelial cell (BREC) and bovine retinal pericyte (BRP) apoptosis and proliferation. METHODS AND RESULTS: Co-cultured BRECs and BRPs were exposed to low (0.3 mL/min) or high (25 mL/min) pulsatile flow for 72 h using a perfused transcapillary culture system. Pulsatile flow increased BREC nitric oxide synthase (eNOS) and cyclooxygenase-2 (COX-2) expression and activity concomitant with a significant decrease in pre pro-endothelin-1 (ET-1) mRNA and peptide. BREC apoptosis was significantly attenuated following exposure to high flow. The inhibition of NOS, COX, and ET receptors significantly reduced the pro-survival effects of flow on BREC. In contrast, BRP apoptosis was significantly enhanced following exposure to high flow. The inhibition of COX and ET receptors significantly attenuated the high flow-induced increase in BRP apoptosis when compared with untreated controls. Treatment of static BREC with NO donor (S-nitroso-N-acetylpenicillamine, SNAP), ET-1, or iloprost inhibited serum deprivation-induced apoptosis, whereas treatment of BRP with ET-1 and iloprost, but not SNAP, was ineffective. High pulsatile flow decreased BRP proliferation, in the absence of any changes in BREC proliferation. CONCLUSION: Increased pulsatile flow promotes BREC survival and enhances BRP apoptosis through the activation of endothelial-derived vasoactive substances. Altered pulsatile flow does not alter BREC proliferation in co culture with BRP, whereas BRP proliferation was significantly decreased at high flow rates. These interactions have important implications for vessel growth and regression during retinal vascular pathogenesis. PMID- 21030536 TI - Effects of backbone substitutions on the conformational behavior of Shigella flexneri O-antigens: implications for vaccine strategy. AB - The O-antigen (O-Ag), the polysaccharide part of the lipopolysaccharide, is the major target of the serotype-specific protective humoral response elicited upon host infection by Shigella flexneri, the main causal agent of the endemic form of bacillary dysentery. The O-Ag repeat units (RUs) of 12 S. flexneri serotypes share the tetrasaccharide backbone ->2)-alpha-l-Rhap-(1 -> 2)-alpha-l-Rhap-(1 -> 3)-alpha-l-Rhap-(1 -> 3)-beta-d-GlcpNAc-(1->, with site-selective glucosylation(s) and/or O-acetylation defining the serotypes. To investigate the conformational basis of serotype specificity, we sampled conformational behaviors during 60 ns of molecular dynamic simulations for oligosaccharides representing three RUs of each one of the O-Ags corresponding to serotypes 1a, 1b, 2a, 2b, 3a, 3b, 4a, 4b, 5a, 5b, X and Y, respectively. The calculated trajectories were checked by nuclear magnetic resonance (NMR) for 1a, 2a, 3a and 5a O-Ags. The simulations predict that in all O-Ags, but 1a and 1b, serotype-specific substitutions of the backbone do not induce any new backbone conformations compared with the linear type O-Ag Y, although they restrain locally the accessible conformational space. Moreover, the influence of any given substituent on the backbone is independent of the eventual presence of other substituents. Finally, only slight differences in conformational behavior between terminal and inner RUs were observed. These results suggest that the reported serotype specificity of the protective immune response is not due to recognition of distinct backbone conformations, but to binding of the serotype-defining substituents in the O-Ag context. The gained knowledge is discussed in terms of impact on the development of a broad-serotype coverage vaccine. PMID- 21030537 TI - N-Glycosylation of total cellular glycoproteins from the human ovarian carcinoma SKOV3 cell line and of recombinantly expressed human erythropoietin. AB - Ovarian carcinoma is the leading cause of death from gynecological cancers in many Western countries. Aberrant glycosylation is an important aspect in malignant transformation and consequently in ovarian cancer. In this study, a detailed structure analysis of the N-linked glycans from total glycoproteins from the SKOV3 ovarian carcinoma cell line and from a recombinantly expressed secretory glycoprotein, erythropoietin (EPO), produced from the same cells has been performed using high-performance anion exchange chromatography with pulsed amperometric detection and matrix-assisted laser desorption/ionization time-of flight mass spectrometry. Total cellular N-glycans contained high-mannose type and proximally fucosylated complex type partially agalactosylated structures. On the other hand, the recombinant human EPO secreted from SKOV3 cells contained predominantly core-fucosylated tetraantennary structures, which were partially lacking one or two galactose residues, and partially contained the LacdiNAc motif. Only minor amounts of di- and triantennary complex-type glycans were found, and high-mannose-type glycans were not present in the secreted EPO protein. A large amount of N-acetylneuraminic acid in alpha2,3-linkage was detected as well. Endogenous glycoproteins were also found to contain the LacdiNAc motif in N-linked glycans. This work contributes to the knowledge of the glycosylation of a human ovarian cancer cell line. It also establishes the basis to further explore high-mannose-type glycans, and the LacdiNAc motif as possible markers of ovarian carcinoma. PMID- 21030539 TI - Exploring novel non-Leloir beta-glucosyltransferases from proteobacteria for modifying linear (beta1->3)-linked gluco-oligosaccharide chains. AB - Over the years several beta-glucan transferases from yeast and fungi have been reported, but enzymes with such an activity from bacteria have not been characterized so far. In this work, we describe the cloning and expression of genes encoding beta-glucosyltransferase domains of glycosyl hydrolase family GH17 from three species of proteobacteria: Pseudomonas aeruginosa PAO1, P. putida KT2440 and Azotobacter vinelandii ATCC BAA-1303. The encoded enzymes of these GH17 domains turned out to have a non-Leloir trans-beta-glucosylation activity, as they do not use activated nucleotide sugar as donor, but transfer a glycosyl group from a beta-glucan donor to a beta-glucan acceptor. More particularly, the activity of the three recombinant enzymes on linear (beta1 -> 3)-linked gluco oligosaccharides (Lam-Glc(4-9)) and their corresponding alditols (Lam-Glc(4-9) ol) was studied. Detailed structural analysis, based on thin-layer chromatography, matrix-assisted laser desorption ionization time-of-flight mass spectrometry, electrospray ionization mass spectrometry, and 1D/2D (1)H and (13)C nuclear magnetic resonance data, revealed diverse product spectra. Depending on the enzyme used, besides (beta1 -> 3)-elongation activity, (beta1 -> 4)- or (beta1 -> 6)-elongation, or (beta1 -> 6)-branching activities were also detected. PMID- 21030538 TI - Oxidative depolymerization of polysaccharides by reactive oxygen/nitrogen species. AB - Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are constantly produced and are tightly regulated to maintain a redox balance (or homeostasis) together with antioxidants (e.g. superoxide dismutase and glutathione) under normal physiological circumstances. These ROS/RNS have been shown to be critical for various biological events including signal transduction, aging, apoptosis, and development. Despite the known beneficial effects, an overproduction of ROS/RNS in the cases of receptor-mediated stimulation and disease-induced oxidative stress can inflict severe tissue damage. In particular, these ROS/RNS are capable of degrading macromolecules including proteins, lipids and nucleic acids as well as polysaccharides, and presumably lead to their dysfunction. The purpose of this review is to highlight (1) chemical mechanisms related to cell free and cell-based depolymerization of polysaccharides initiated by individual oxidative species; (2) the effect of ROS/RNS-mediated depolymerization on the successive cleavage of the glycosidic linkage of polysaccharides by glycoside hydrolases; and (3) the potential biological outcome of ROS/RNS-mediated depolymerization of polysaccharides. PMID- 21030540 TI - Composition and structure elucidation of human milk glycosaminoglycans. AB - To date, there is no complete structural characterization of human milk glycosaminoglycans (GAGs) available nor do any data exist on their composition in bovine milk. Total GAGs were determined on extracts from human and bovine milk. Samples were subjected to digestion with specific enzymes, treated with nitrous acid, and analyzed by agarose-gel electrophoresis and high-performance liquid chromatography for their structural characterization. Quantitative analyses yielded ~7 times more GAGs in human milk than in bovine milk. In particular, galactosaminoglycans, chondroitin sulfate (CS) and dermatan sulfate (DS), were found to differ considerably from one type of milk to the other. In fact, hardly any DS was observed in human milk, but a low-sulfated CS having a very low charge density of 0.36 was found. On the contrary, bovine milk galactosaminoglycans were demonstrated to be composed of ~66% DS and 34% CS for a total charge density of 0.94. Structural analysis performed by heparinases showed a prevalence of fast moving heparin over heparan sulfate, accounting for ~30-40% of total GAGs in both milk samples and showing lower sulfation in human (2.03) compared with bovine (2.28). Hyaluronic acid was found in minor amounts. This study offers the first full characterization of the GAGs in human milk, providing useful data to gain a better understanding of their physiological role, as well as of their fundamental contribution to the health of the newborn. PMID- 21030541 TI - Should helicopters have a hoist or 'long-line' capability to perform mountain rescue in the UK? AB - OBJECTIVES: To determine how far mountain rescue casualties in the UK have to be carried and the impact of adding a hoist or 'long-line' to helicopters operating in this environment. DESIGN: Retrospective analysis of mountain rescue incidents. SETTING: Pre-hospital, mountain rescue service based in Patterdale, English Lake District. PARTICIPANTS: Casualties between 1 January 2006 and 31 December 2008 that required stretcher evacuation. Casualties directly accessible by a road ambulance were excluded. MAIN OUTCOME: The horizontal and vertical distance of the evacuation route to an agreed helicopter-landing site, and its technical character. Direct access to the incident site by a helicopter with a hoist or long-line capability was determined. RESULTS: 119 casualties were identified. The median horizontal and vertical evacuation distances were 250 m and -30 m respectively. The proposed manual carrying distances were <=100 m in 33/119 (28%), between 101 and 400 m in 60/119 (50%) and >400 m in 26/119 (22%) of casualties. 13/119 (11%) casualties were in a position where direct access to the incident site would not have been possible with a helicopter equipped with a hoist or long-line. 31/119 (26%) casualties required a technical evacuation with the use of ropes. CONCLUSIONS: Using the criteria that all casualties requiring a technical rescue or >400 m evacuation route to an appropriate helicopter-landing site, 34% of casualties could have been rescued using a hoist or long-line with an expected reduction in the pre-hospital time. Helicopters working in UK mountain rescue should be equipped to international standards. PMID- 21030542 TI - Demand and capacity planning in the emergency department: how to do it. AB - BACKGROUND: Unless emergency departments have adequate capacity to meet demand, they will fail to meet clinical and performance standards and will be operating in the 'coping zone'. This carries risks both for staff and patients. METHODS: As part of a quality improvement programme, the authors undertook an in-depth analysis of demand and capacity for an emergency department in the UK. The paper describes this rigorous approach to capacity planning, which draws on techniques from other industries. DISCUSSION AND CONCLUSIONS: Proper capacity planning is vital, but is often poorly done. Planning using aggregated data will lead to inadequate capacity. Understanding demand, and particularly the variation in that demand, is critical to success. Analysis of emergency department demand and capacity is the first step towards effective workforce planning and process redesign. PMID- 21030543 TI - Time lag to hospitalisation and the associated determinants in patients with acute myocardial infarction: the Takashima AMI Registry, Japan. AB - BACKGROUND: Prompt initiation of treatment is the cornerstone in the management of patients with acute myocardial infarction (AMI). The time lags for AMI hospitalisations were examined to identify the factors influencing the interval. METHODS: Time lag information was available for 273 men and 148 women from the Takashima AMI Registry during 1988-2006. Multivariate regression analyses were performed to evaluate the factors influencing early and late admission. RESULTS: The median time to hospitalisation was 2 h (mean 6.1, SD 18.7). Within 2 h of onset, 59.8% patients arrived and 20.6% arrived during the 2-6 h interval. A substantial number of patients (19.6%) arrived after 6 h and onwards. A time lag of >2 h in hospital admission was significantly influenced by history of hypertension, angina, presence of syncope as an initial symptom and time of AMI onset. A time lag of >6 h shared similar characteristics except for presence of history of angina. CONCLUSIONS: About one-fifth of patients with AMI have prolonged time lag in the study population. Future research intervention and health promotion activities should focus on achieving a reduction in presentation delays. PMID- 21030544 TI - Emergency department staff knowledge of massive transfusion for trauma: the need for an evidence based protocol. AB - INTRODUCTION: Uncontrolled haemorrhage is the leading cause of potentially reversible early in-hospital death following trauma. Approximately 25% of trauma patients arriving in the emergency department have evidence of early coagulopathy. It is vital that staff within the emergency department understand the basic pathophysiological consequences of massive blood loss in trauma and are familiar with when and how to administer blood and specific blood components in trauma resuscitation. METHODS: A structured questionnaire designed to test knowledge of the use of blood and blood components in trauma resuscitation was distributed to the emergency physicians attending a regional conference in the South West of England. The questionnaire consisted of 16 questions, both multiple choice and short answer format, referenced via Medline. RESULTS: 32/32 questionnaires distributed were completed and returned. Massive transfusion protocols existed in 4/11 hospitals surveyed. 5/32 doctors were able to define the term 'massive transfusion' while 9/32, 6/32 and 3/32 were consistent with current guidelines in their prescription of platelets, fresh frozen plasma, and cryoprecipitate. 20/32 were consistent with current guidelines in identifying optimal haemoglobin levels. When asked more specifically about blood component therapy, 18/32 correctly identified target fibrinogen levels, 27/32 knew that fibrinogen is a component of fresh frozen plasma or cryoprecipitate and 1/32 correctly identified that fibrinogen is a component of both. 10/32 identified indications for beriplex and 5/32 doctors correctly identified indications for the use of recombinant factor VIIa. 20/32 doctors guessed >50% of the answers and the remaining 12/32 guessed 50%. CONCLUSIONS: The survey found that emergency physicians lacked core knowledge about the use of blood and blood component therapy in the context of massive haemorrhage following trauma. Doctors were unaware of how to prevent and treat early coagulopathy. Educational resources specifically for use by emergency physicians are limited on this topic. The use of massive transfusion protocols--that standardised blood component therapy is automatically delivered at specific points within resuscitation--would not only guide doctors, but be a clear step towards minimising the complications associated with massive transfusion. PMID- 21030545 TI - Procedural sedation and recall in the emergency department: the relationship between depth of sedation and patient recall and satisfaction (a pilot study). AB - This study aimed to determine the prevalence of patient recall and its relationship between sedation depth, pain and patient satisfaction in a sample of patients receiving procedural sedation in the emergency department. Recall, pain and patient satisfaction were measured on a scale of 0-10 and sedation depth a scale of 1-4 (American Society of Anesthesiologists sedation scale). Spearman's correlation test showed sedation depth was significantly related to recall (Spearman's rho = -0.511, p<0.05) specifically with midazolam use (rho = -0.857, p<0.01). Increased recall was associated with higher pain scores (rho = 0.683, p<0.001) and lower patient satisfaction (rho = -0.785, p<0.001). PMID- 21030546 TI - Weather inference and daily demand for emergency ambulance services. AB - AIM: To examine weather effects on the daily demand for ambulance services in Hong Kong. METHODS: Over 6 million cases of emergency attendance from May 2006 through April 2009 (3 years) were obtained from the Hospital Authority in Hong Kong. These cases were further stratified by age, triage levels, hospital admission status, comprehensive social security assistance (CSSA) recipients and gender. The stratification was used to correlate against weather factors to assess the dependency of these variables and their effects on the daily number of ambulance calls. Adjusted-R(2) values obtained from the regression analysis were used as a measure for evaluating predictability. RESULTS: The adjusted-R(2) of emergency cases by age groups showed proportional correlation with weather factors, which was more significant in older patients (0.76, p<0.01) than young patients (0.10, p<0.05). Furthermore, patients with more severe conditions were shown to have a higher adjusted-R(2) (0.63, p<0.05 for critical as opposed to 0 for non-urgent patients). Weather effects were also found more significant in women (0.50, p<0.01) and CSSA recipients (0.54, p<0.01) when compared against their corresponding reference groups (respectively men at 0.46, p<0.01 and non CSSA recipients at 0.45, p<0.01). Moreover, average temperature appeared to be a major weather effect. CONCLUSIONS: The presence of strong weather effects among different target groups indicates possibility for the development of a short-term forecast system of daily ambulance demand using weather variables. The availability of such a forecast system would render more effective deployment of the ambulance services to meet the unexpected increase in service demands. PMID- 21030547 TI - Clinical governance and prehospital care in the UK. PMID- 21030548 TI - Emergency head injury imaging: implementing NICE 2007 in a tertiary neurosciences centre and a busy district general hospital. AB - BACKGROUND: Head injuries are a common emergency department (ED) presentation. The National Institute for Health and Clinical Excellence (NICE) updated its guidance in September 2007 regarding imaging required for patients with head injuries. METHODS: A two-centre observational ED study was carried out, examining imaging practice in adults and children with head injuries attending pre guideline and post-guideline implementation. Guideline implementation occurred through a formal implementation programme at the teaching hospital, and informally at the district general hospital (DGH). Retrospective extraction took place of prospectively recorded data case records and radiology department imaging registers. Pre-implementation data were collected from Salford Royal Foundation NHS Trust (SRFT) from January and February 2008 and post implementation data in May 2008. Post-implementation data was collated from Royal Bolton Hospital Foundation NHS Trust (RBFT) from September to November 2007. Compliance with NICE 2007 was the primary outcome assessed. RESULTS: With the implementation of NICE 2007 guidelines at SRFT, a significant increase in compliance from 94.2% (92.9-95.5) to 98.8% (98.2-99.3) was observed for adults requiring head CTs, with an overall trend to improved clinical practice in the adult patient populations. However, a significant number of children (SRFT 68.7% and RBFT 77.1%) did not receive the indicated head CT scan following a head injury, after implementation of the guidelines. CONCLUSIONS: The SRFT implementation strategy employed was successful for adults, with the overall trend to increased clinical compliance post-guideline introduction. Evidence of a reluctance to adhere to the NICE recommendations for children indicated for CT head scan after a head injury was observed. PMID- 21030549 TI - Using 'reverse triage' to create hospital surge capacity: Royal Darwin Hospital's response to the Ashmore Reef disaster. AB - This report analyses the impact of reverse triage, as described by Kelen, to rapidly assess the need for continuing inpatient care and to expedite patient discharge to create surge capacity for disaster victims. The Royal Darwin Hospital was asked to take up to 30 casualties suffering from blast injuries from a boat carrying asylum seekers that had exploded 840 km west of Darwin. The hospital was full, with a backlog of cases awaiting admission in the emergency department. The Disaster Response Team convened at 10:00 to develop the surge capacity to admit up to 30 casualties. By 14:00, 56 beds (16% of capacity) were predicted to be available by 18:00. The special circumstances of a disaster enabled staff to suspend their usual activities and place a priority on triaging inpatients' suitability for discharge. The External Disaster Plan was activated and response protocols were followed. Normal elective activity was suspended. Multidisciplinary teams immediately assessed patients and completed the necessary clinical and administrative requirements to discharge them quickly. As per the Plan there was increased use of community care options: respite nursing home beds and community nursing services. Through a combination of cancellation of all planned admissions, discharging 19 patients at least 1 day earlier than planned and discharging all patients earlier in the day surge capacity was made available in Royal Darwin Hospital to accommodate blast victims. Notably, reverse triage resulted in no increase in clinical risk with only one patient who was discharged early returning for further treatment. PMID- 21030550 TI - Lung ultrasound is an accurate diagnostic tool for the diagnosis of pneumonia in the emergency department. AB - OBJECTIVE: The aim of this study was to evaluate the diagnostic accuracy of bedside lung ultrasound and chest radiography (CXR) in patients with suspected pneumonia compared with CT scan and final diagnosis at discharge. Design A prospective clinical study. METHODS: Lung ultrasound and CXR were performed in sequence in adult patients admitted to the emergency department (ED) for suspected pneumonia. A chest CT scan was performed during hospital stay when clinically indicated. RESULTS: 120 patients entered the study. A discharge diagnosis of pneumonia was confirmed in 81 (67.5%). The first CXR was positive in 54/81 patients (sensitivity 67%; 95% CI 56.4% to 76.9%) and negative in 33/39 (specificity 85%; 95% CI 73.3% to 95.9%), whereas lung ultrasound was positive in 80/81 (sensitivity 98%; 95% CI 93.3% to 99.9%) and negative in 37/39 (specificity 95%; 95% CI 82.7% to 99.4%). A CT scan was performed in 30 patients (26 of which were positive for pneumonia); in this subgroup the first CXR was diagnostic for pneumonia in 18/26 cases (sensitivity 69%), whereas ultrasound was positive in 25/26 (sensitivity 96%). The feasibility of ultrasound was 100% and the examination was always performed in less than 5 min. CONCLUSIONS: Bedside chest ultrasound is a reliable tool for the diagnosis of pneumonia in the ED, probably being superior to CXR in this setting. It is likely that its wider use will allow a faster diagnosis, conducive to a more appropriate and timely therapy. PMID- 21030551 TI - Rehearsing for the show: The role of pilot study reports for developing nursing science. PMID- 21030553 TI - Discovery of recurrent t(6;7)(p25.3;q32.3) translocations in ALK-negative anaplastic large cell lymphomas by massively parallel genomic sequencing. AB - The genetics of peripheral T-cell lymphomas are poorly understood. The most well characterized abnormalities are translocations involving ALK, occurring in approximately half of anaplastic large cell lymphomas (ALCLs). To gain insight into the genetics of ALCLs lacking ALK translocations, we combined mate-pair DNA library construction, massively parallel ("Next Generation") sequencing, and a novel bioinformatic algorithm. We identified a balanced translocation disrupting the DUSP22 phosphatase gene on 6p25.3 and adjoining the FRA7H fragile site on 7q32.3 in a systemic ALK-negative ALCL. Using fluorescence in situ hybridization, we demonstrated that the t(6;7)(p25.3;q32.3) was recurrent in ALK-negative ALCLs. Furthermore, t(6;7)(p25.3;q32.3) was associated with down-regulation of DUSP22 and up-regulation of MIR29 microRNAs on 7q32.3. These findings represent the first recurrent translocation reported in ALK-negative ALCL and highlight the utility of massively parallel genomic sequencing to discover novel translocations in lymphoma and other cancers. PMID- 21030554 TI - Predictive factors for outcome and response in patients treated with second generation tyrosine kinase inhibitors for chronic myeloid leukemia in chronic phase after imatinib failure. AB - We assessed the predictive factors for outcome and response in 123 patients with chronic myeloid leukemia in chronic phase treated with second-generation tyrosine kinase inhibitors (TKIs) after imatinib failure. Better event-free survival rates with second-generation TKI therapy were associated with a previous cytogenetic response to imatinib (P < .001) and a performance status of 0 (P = .001). Patients with 0, 1, or 2 adverse factors had 2-year event-free survival rates of 78%, 49%, and 20% (P < .001), respectively; 2-year overall survival rates of 95%, 85%, and 40%, (P = .002), respectively; and a 12-month probability of achieving a major cytogenetic response of 64%, 36%, and 20% (P = .007), respectively. In conclusion, patients with poor performance status and no previous cytogenetic response to imatinib therapy have a low likelihood of responding to second generation TKI with poor event-free survival and therefore should be offered additional treatment options. This scoring system could serve to advise patients of their prognosis and treatment options, as well as to evaluate the benefit of newer alternate options. PMID- 21030555 TI - Mechanism of transfusion-related acute lung injury induced by HLA class II antibodies. AB - Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion associated mortality in the United States and other countries. In most TRALI cases, human leukocyte antigen (HLA) class II antibodies are detected in implicated donors. However, the corresponding antigens are not present on the cellular key players in TRALI: neutrophils and endothelium. In this study, we identify monocytes as a primary target in HLA class II-induced TRALI. Monocytes become activated when incubated with matched HLA class II antibodies and are capable of activating neutrophils, which, in turn, can induce disturbance of an endothelial barrier. In an ex vivo rodent model, HLA class II antibody-dependent monocyte activation leads to severe pulmonary edema in a relevant period of time, whenever neutrophils are present and the endothelium is preactivated. Our data suggest that in most TRALI cases, monocytes are cellular key players, because HLA class II antibodies induce TRALI by a reaction cascade initiated by monocyte activation. Furthermore, our data support the previous assumption that TRALI pathogenesis follows a threshold model. Having identified the biologic mechanism of HLA class II antibody-induced TRALI, strategies to avoid plasma from immunized donors, such as women with a history of pregnancy, appear to be justified preventive measures. PMID- 21030556 TI - Endothelial LSP1 is involved in endothelial dome formation, minimizing vascular permeability changes during neutrophil transmigration in vivo. AB - The endothelium actively participates in neutrophil migration out of the vasculature via dynamic, cytoskeleton-dependent rearrangements leading to the formation of transmigratory cups in vitro, and to domes that completely surround the leukocyte in vivo. Leukocyte-specific protein 1 (LSP1), an F-actin-binding protein recently shown to be in the endothelium, is critical for effective transmigration, although the mechanism has remained elusive. Herein we show that endothelial LSP1 is expressed in the nucleus and cytosol of resting endothelial cells and associates with the cytoskeleton upon endothelial activation. Two photon microscopy revealed that endothelial LSP1 was crucial for the formation of endothelial domes in vivo in response to neutrophil chemokine keratinocyte derived chemokine (KC) as well as in response to endogenously produced chemokines stimulated by cytokines (tumor necrosis factor alpha [TNFalpha] or interleukin 1beta [IL-1beta]). Endothelial domes were significantly reduced in Lsp1(-/-) compared with wild-type (WT) mice. Lsp1(-/-) animals not only showed impaired neutrophil emigration after KC and TNFalpha stimulation, but also had disproportionate increases in vascular permeability. We demonstrate that endothelial LSP1 is recruited to the cytoskeleton in inflammation and plays an important role in forming endothelial domes thereby regulating neutrophil transendothelial migration. The permeability data may underscore the physiologic relevance of domes and the role for LSP1 in endothelial barrier integrity. PMID- 21030557 TI - Ewing sarcoma gene Ews regulates hematopoietic stem cell senescence. AB - The longevity of organisms is maintained by stem cells. If an organism loses the ability to maintain a balance between quiescence and differentiation in the stem/progenitor cell compartment due to aging and/or stress, this may result in death or age-associated diseases, including cancer. Ewing sarcoma is the most lethal bone tumor in young patients and arises from primitive stem cells. Here, we demonstrated that endogenous Ewing sarcoma gene (Ews) is indispensable for stem cell quiescence, and that the ablation of Ews promotes the early onset of senescence in hematopoietic stem progenitor cells. The phenotypic and functional changes in Ews-deficient stem cells were accompanied by an increase in senescence associated beta-galactosidase staining and a marked induction of p16(INK4a) compared with wild-type counterparts. With its relevance to cancer and possibly aging, EWS is likely to play a significant role in maintaining the functional capacity of stem cells and may provide further insight into the complexity of Ewing sarcoma in the context of stem cells. PMID- 21030559 TI - Increased thioredoxin-1 production in human naturally occurring regulatory T cells confers enhanced tolerance to oxidative stress. AB - Levels of regulatory T cells (Tregs) are increased in different cancer types as well as in inflammatory diseases, such as rheumatoid arthritis. Treg accumulation may result from aberrant proliferation and trafficking as well as greater resilience to oxidative stress compared with conventional T cells. This enhanced antioxidative capacity of Tregs possibly serves as feedback inhibition during inflammation and prevents uncontrolled immune reactions by favoring survival of suppressor rather than effector cells. In this study, we demonstrate that human Tregs express and secrete higher levels of thioredoxin-1, a major antioxidative molecule. Thioredoxin-1 has an essential role in maintaining their surface thiol density as the first line of antioxidative defense mechanisms and is sensitive to proinflammatory stimuli, mainly tumor necrosis factor-alpha, in a nuclear factor kappaB-dependent fashion. The antiapoptotic and oncogenic potential of (secreted) Trx-1 suggests that it may exert effects in Tregs beyond redox regulation. PMID- 21030560 TI - Acute myeloid leukemia with mutated nucleophosmin (NPM1): is it a distinct entity? AB - After the discovery of NPM1-mutated acute myeloid leukemia (AML) in 2005 and its subsequent inclusion as a provisional entity in the 2008 World Health Organization classification of myeloid neoplasms, several controversial issues remained to be clarified. It was unclear whether the NPM1 mutation was a primary genetic lesion and whether additional chromosomal aberrations and multilineage dysplasia had any impact on the biologic and prognostic features of NPM1-mutated AML. Moreover, it was uncertain how to classify AML patients who were double mutated for NPM1 and CEBPA. Recent studies have shown that: (1) the NPM1 mutant perturbs hemopoiesis in experimental models; (2) leukemic stem cells from NPM1 mutated AML patients carry the mutation; and (3) the NPM1 mutation is usually mutually exclusive of biallelic CEPBA mutations. Moreover, the biologic and clinical features of NPM1-mutated AML do not seem to be significantly influenced by concomitant chromosomal aberrations or multilineage dysplasia. Altogether, these pieces of evidence point to NPM1-mutated AML as a founder genetic event that defines a distinct leukemia entity accounting for approximately one-third of all AML. PMID- 21030558 TI - Combination immunotherapy using adoptive T-cell transfer and tumor antigen vaccination on the basis of hTERT and survivin after ASCT for myeloma. AB - In a phase 1/2 two-arm trial, 54 patients with myeloma received autografts followed by ex vivo anti-CD3/anti-CD28 costimulated autologous T cells at day 2 after transplantation. Study patients positive for human leukocyte antigen A2 (arm A, n = 28) also received pneumococcal conjugate vaccine immunizations before and after transplantation and a multipeptide tumor antigen vaccine derived from the human telomerase reverse transcriptase and the antiapoptotic protein survivin. Patients negative for human leukocyte antigen A2 (arm B, n = 26) received the pneumococcal conjugate vaccine only. Patients exhibited robust T cell recoveries by day 14 with supraphysiologic T-cell counts accompanied by a sustained reduction in regulatory T cells. The median event-free survival (EFS) for all patients is 20 months (95% confidence interval, 14.6-24.7 months); the projected 3-year overall survival is 83%. A subset of patients in arm A (36%) developed immune responses to the tumor antigen vaccine by tetramer assays, but this cohort did not exhibit better EFS. Higher posttransplantation CD4(+) T-cell counts and a lower percentage of FOXP3(+) T cells were associated with improved EFS. Patients exhibited accelerated polyclonal immunoglobulin recovery compared with patients without T-cell transfers. Adoptive transfer of tumor antigen vaccine-primed and costimulated T cells leads to augmented and accelerated cellular and humoral immune reconstitution, including antitumor immunity, after autologous stem cell transplantation for myeloma. This study was registered at www.clinicaltrials.gov as NCT00499577. PMID- 21030561 TI - Active Rac1 improves pathologic VEGF neovessel architecture and reduces vascular leak: mechanistic similarities with angiopoietin-1. AB - Architecturally defective, leaky blood vessels typify pathologic angiogenesis induced by vascular endothelial growth factor-A (VEGF-A). Such neovascular defects aggravate disease pathology and seriously compromise the therapeutic utility of VEGF. Endothelial cell (EC) transduction with active L61Rac1 strongly improved VEGF-driven angiogenesis in vivo as measured by increased neovascular density, enhanced lumen formation, and reduced vessel leakiness. Conversely, transduction with dominant-negative N17Rac1 strongly inhibited neovascularization. In vitro, active L61Rac1 promoted organization of cortical actin filaments and vascular cords and improved EC-EC junctions, indicating that improved cytoskeletal dynamics are important to the mechanism by which active L61Rac1 rectifies VEGF-driven angiogenesis. SEW2871, a sphingosine 1-phosphate receptor-1 agonist that activates Rac1 in ECs, improved cord formation and EC-EC junctions in vitro similarly to active L61Rac. Moreover, SEW2871 administration in vivo markedly improved VEGF neovessel architecture and reduced neovascular leak. Angiopoietin-1, a cytokine that "normalizes" VEGF neovessels in vivo, activated Rac1 and improved cord formation and EC-EC junctions in vitro comparably to active L61Rac1, and a specific Rac1 inhibitor blocked these effects. These studies distinguish augmentation of Rac1 activity as a means to rectify the pathologic angioarchitecture and dysfunctionality of VEGF neovessels, and they identify a rational pharmacologic strategy for improving VEGF angiogenesis. PMID- 21030562 TI - Vaccination with dendritic cell/tumor fusion cells results in cellular and humoral antitumor immune responses in patients with multiple myeloma. AB - We have developed a tumor vaccine in which patient-derived myeloma cells are chemically fused with autologous dendritic cells (DCs) such that a broad spectrum of myeloma-associated antigens are presented in the context of DC-mediated costimulation. We have completed a phase 1 study in which patients with multiple myeloma underwent serial vaccination with the DC/multiple myeloma fusions in conjunction with granulocyte-macrophage colony-stimulating factor. DCs were generated from adherent mononuclear cells cultured with granulocyte-macrophage colony-stimulating factor, interleukin-4, and tumor necrosis factor-alpha and fused with myeloma cells obtained from marrow aspirates. Vaccine generation was successful in 17 of 18 patients. Successive cohorts were treated with 1 * 10(6), 2 * 10(6), and 4 * 10(6) fusion cells, respectively, with 10 patients treated at the highest dose level. Vaccination was well tolerated, without evidence of dose limiting toxicity. Vaccination resulted in the expansion of circulating CD4 and CD8 lymphocytes reactive with autologous myeloma cells in 11 of 15 evaluable patients. Humoral responses were documented by SEREX (Serologic Analysis of Recombinant cDNA Expression Libraries) analysis. A majority of patients with advanced disease demonstrated disease stabilization, with 3 patients showing ongoing stable disease at 12, 25, and 41 months, respectively. Vaccination with DC/multiple myeloma fusions was feasible and well tolerated and resulted in antitumor immune responses and disease stabilization in a majority of patients. PMID- 21030563 TI - NKp46 and DNAM-1 NK-cell receptors drive the response to human cytomegalovirus infected myeloid dendritic cells overcoming viral immune evasion strategies. AB - Information on natural killer (NK)-cell receptor-ligand interactions involved in the response to human cytomegalovirus (HCMV) is limited and essentially based on the study of infected fibroblasts. Experimental conditions were set up to characterize the NK response to HCMV-infected myeloid dendritic cells (DCs). Monocyte-derived DCs (moDCs) infected by the TB40/E HCMV strain down-regulated the expression of human leukocyte antigen class I molecules and specifically activated autologous NK-cell populations. NKG2D ligands appeared virtually undetectable in infected moDCs, reflecting the efficiency of immune evasion mechanisms, and explained the lack of antagonistic effects of NKG2D-specific monoclonal antibody. By contrast, DNAM-1 and DNAM-1 ligands (DNAM-1L)-specific monoclonal antibodies inhibited the NK response at 48 hours after infection, although the impact of HCMV-dependent down-regulation of DNAM-1L in infected moDCs was perceived at later stages. moDCs constitutively expressed ligands for NKp46 and NKp30 natural cytotoxicity receptors, which were partially reduced on HCMV infection; yet, only NKp46 appeared involved in the NK response. In contrast to previous reports in fibroblasts, human leukocyte antigen-E expression was not preserved in HCMV-infected moDCs, which triggered CD94/NKG2A(+) NK-cell activation. The results provide an insight on key receptor-ligand interactions involved in the NK-cell response against HCMV-infected moDCs, stressing the importance of the dynamics of viral immune evasion mechanisms. PMID- 21030564 TI - Factors affecting healing rates after arthroscopic double-row rotator cuff repair. AB - BACKGROUND: Double-row arthroscopic rotator cuff repairs were developed to improve initial biomechanical strength of repairs to improve healing rates. Despite biomechanical improvements, failure of healing remains a clinical problem. PURPOSE: To evaluate the anatomical results after double-row arthroscopic rotator cuff repair with ultrasound to determine postoperative repair integrity and the effect of various factors on tendon healing. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Forty-eight patients (49 shoulders) who had a complete arthroscopic rotator cuff repair (double-row technique) were evaluated with ultrasound at a minimum of 6 months after surgery. Outcome was evaluated at a minimum of 1-year follow-up with standardized history and physical examination, visual analog scale for pain, active forward elevation, and preoperative and postoperative shoulder scores according to the system of the American Shoulder and Elbow Surgeons and the Simple Shoulder Test. Quantitative strength was measured postoperatively. RESULTS: Ultrasound and physical examinations were performed at a minimum of 6 months after surgery (mean, 16 months; range, 6 to 36 months) and outcome questionnaire evaluations at a minimum of 12 months after surgery (mean, 29 months; range, 12 to 55 months). Of 49 repairs, 25 (51%) were healed. Healing rates were 67% in single-tendon tears (16 of 24 shoulders) and 36% in multitendon tears (9 of 25 shoulders). Older age and longer duration of follow-up were correlated with poorer tendon healing (P < .03). Visual analog scale for pain, active forward elevation, American Shoulder and Elbow Surgeons scores, and Simple Shoulder Test scores all had significant improvement from baseline after repair (P < .0001). CONCLUSION: Increased age and longer duration of follow-up were associated with lower healing rates after double-row rotator cuff repair. The biological limitation at the repair site, as reflected by the effects of age on healing, appears to be the most important factor influencing tendon healing, even after maximizing repair biomechanical strength with a double-row construct. PMID- 21030565 TI - Heating up cold agglutinins. AB - In this issue of Blood, Berentsen and coworkers describe a high response rate which is durable in some patients who receive combination fludarabine and rituximab for chronic cold agglutinin disease (CAD). If confirmed, this is a significant advance in therapy for a frequently difficult clinical problem. PMID- 21030566 TI - To B or not to B. AB - Recent data from mouse models suggest that some phenotypes of X-linked lymphoproliferative disease (XLP) result from impaired T:B-cell interactions.Hislop and colleagues now provide evidence that this may contribute to abnormal responses to Epstein-Barr virus (EBV) in XLP. PMID- 21030567 TI - Red or green? Enucleation traffic light. AB - In this issue of Blood, Keerthivasan and colleagues provide compelling support for the novel concept that the formation, movement, and fusion of endocytic vesicles in the region between the extruding nucleus and nascent reticulocyte are critical steps in erythroblast enucleation. PMID- 21030568 TI - "Ta panta rhei". AB - In this issue of Blood, Evans et al report that fractal analysis of the mechanical properties of whole-blood clots defines a unique property of the incipient clot that can be used as a functional biomarker of hemostasis. PMID- 21030569 TI - GPVI and the not so eager cleaver. AB - Platelets control their responsiveness, in part, by shedding adhesion and signaling receptors from their surface. The molecular mechanism by which this occurs, however,is incompletely understood. In this issue of Blood, Bender and colleagues make judicious use of mice genetically deficient in selected candidate proteases to shed new light on the unexpected complexity of ectodomain shedding. PMID- 21030570 TI - Transplant survivorship: a call to arms. AB - In this issue of Blood, Sun and colleagues from the Bone Marrow Transplant Survivors Study report the chronic health outcomes of more than 1000 survivors of stem cell transplantation. Their results demonstrate a significant burden of chronic conditions among survivors. PMID- 21030571 TI - Possible misinterpretation of the mode of action of therapeutic antibodies in vitro: homotypic adhesion and flow cytometry result in artefactual direct cell death. PMID- 21030572 TI - Hereditary thrombocytosis not as innocent as thought? Development into acute leukemia and myelofibrosis. PMID- 21030574 TI - Posttransplant recurrence of primary glomerulonephritis. AB - All forms of primary GN may recur after kidney transplantation and potentially jeopardize the survival of the graft. IgA nephritis (IgAN) may recur in approximately one third of patients, more frequently in younger patients and in those with a rapid progression of the original disease. However, with the exception of few patients with rapid progression, there is no evidence that recurrence of IgAN has a deleterious effect on graft survival at least up to 10 years. Recurrence of focal segmental glomerulosclerosis (FSGS) is often associated with nephrotic proteinuria and is more frequent in children, in patients with rapid progression of the original disease, and in those who lost a previous transplant from recurrence. The natural course of recurrent FSGS is usually unfavorable. Early and intensive plasmapheresis may obtain complete or partial response in several patients. Good results have also been reported with rituximab. Idiopathic membranous nephropathy (IMN) may recur in 30% to 40% of patients. The graft survival in patients with IMN is not different than that of patients with other renal diseases. Good results with rituximab have been reported. Membranoproliferative GN (MPGN) may recur in 27% to 65% of patients. The recurrence is more frequent and the prognosis is more severe in type II MPGN. Although recurrent GN is relatively frequent and may worsen the outcome of renal allografts in some patients, its effect is diluted by several other risk-factors that may have a greater effect than recurrent GN on the long-term graft survival. PMID- 21030575 TI - Contribution of residual function to removal of protein-bound solutes in hemodialysis. AB - BACKGROUND AND OBJECTIVES: This study evaluated the contribution of residual function to the removal of solutes for which protein binding limits clearance by hemdialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Solute concentrations were measured in 25 hemodialysis patients with residual urea clearances ranging from 0.1 to 6.2 ml/min per 1.73 m2. Mathematical modeling assessed the effect of residual function on time-averaged solute concentrations. RESULTS: Dialytic clearances of the protein-bound solutes p-cresol sulfate, indoxyl sulfate, and hippurate were reduced in proportion to the avidity of binding and averaged 8+/ 2, 10+/-3, and 44+/-13% of the dialytic urea clearance. For each bound solute, the residual clearance was larger in relation to the residual urea clearance. Residual kidney function therefore removed a larger portion of each of the bound solutes than of urea. Increasing residual function was associated with lower plasma levels of p-cresol sulfate and hippurate but not indoxyl sulfate. Wide variation in solute generation tended to obscure the dependence of plasma solute levels on residual function. Mathematical modeling that corrected for this variation indicated that increasing residual function will reduce the plasma level of each of the bound solutes more than the plasma level of urea. CONCLUSIONS: In comparison to urea, solutes than bind to plasma proteins can be more effectively cleared by residual function than by hemodialysis. Levels of such solutes will be lower in patients with residual function than in patients without residual function even if the dialysis dose is reduced based on measurement of residual urea clearance in accord with current guidelines. PMID- 21030576 TI - Dialysis fistula or graft: the role for randomized clinical trials. AB - The Fistula First Initiative has strongly encouraged nephrologists, vascular access surgeons, and dialysis units in the United States to make valiant efforts to increase fistula use in the hemodialysis population. Unfortunately, the rigid "fistula first" recommendations are not based on solid, current, evidence-based data and may be harmful to some hemodialysis patients by subjecting them to prolonged catheter dependence with its attendant risks of bacteremia and central vein stenosis. Once they are successfully cannulated for dialysis, fistulas last longer than grafts and require fewer interventions to maintain long-term patency for dialysis. However, fistulas have a much higher primary failure rate than grafts, require more interventions to achieve maturation, and entail longer catheter dependence, thereby leading to more catheter-related complications. Given the tradeoffs between fistulas and grafts, there is equipoise about their relative merits in patients with moderate to high risk of fistula nonmaturation. The time is right for definitive, large, multicenter randomized clinical trials to compare fistulas and grafts in various subsets of chronic kidney disease patients. Until the results of such clinical trials are known, the optimal vascular access for a given patients should be determined by the nephrologist and access surgeon by taking into account (1) whether dialysis has been initiated, (2) the patient's life expectancy, (3) whether the patient has had a previous failed vascular access, and (4) the likelihood of fistula nonmaturation. Careful clinical judgment should optimize vascular access outcomes and minimize prolonged catheter dependence among hemodialysis patients. PMID- 21030577 TI - Renal, ocular, and neuromuscular involvements in patients with CLDN19 mutations. AB - BACKGROUND AND OBJECTIVES: The objective of this study was to describe the renal and extrarenal findings in patients with recessively inherited familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) associated with CLDN19 mutations. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Medical records of three patients from two French unrelated families with CLDN19 mutations were retrospectively examined. RESULTS: Direct sequencing of CLDN19 identified a known variant (p.Gly20Asp) in all patients and a new missense mutation (p.Val44Met) in one (compound heterozygous). The patients' renal phenotype closely mimicked CLDN16-related nephropathy: low serum Mg2+ (<0.65 mmol/L) despite oral supplementation, hypercalciuria partly thiazide-sensitive, and progressive renal decline with ESRD reached at age 16 and 22 years in two individuals. Primary characteristics (failure to thrive, recurrent urinary tract infections, or abdominal pain), age at onset (0.8 to 16 years), and rate of renal decline were highly heterogeneous. Ocular involvement was identified in all patients, although two patients did not have visual loss. Additionally, exercise intolerance with pain, weakness, and electromyographical alterations mimicking a Ca2+/K+ channelopathy (pattern V) were observed in two of three individuals. These features persisted despite the normalization of serum K+ and Mg2+ after renal transplantation. CONCLUSIONS: Ocular manifestations, even subtle, and exercise intolerance mimicking mild to moderate periodic paralysis are two symptoms that need to be searched for in patients with FHHNC and may indicate CLDN19 mutations. PMID- 21030578 TI - Continuous flow peritoneal dialysis: first experience in children with acute renal failure. AB - BACKGROUND AND OBJECTIVES: Acute renal failure can be treated with different dialysis modalities, depending on patient characteristics and hospital resources. Peritoneal dialysis (PD) can be first choice in situations like hypotension, disturbed coagulation, or difficult venous access. The main disadvantage of PD is the relatively limited efficacy. The aim of this study was to investigate whether continuous flow peritoneal dialysis (CFPD) is a more effective treatment than conventional PD in acute renal failure. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A pilot study was performed at The Red Cross University Hospital in Cape Town in six patients. Patients were treated with both CFPD and conventional PD for 8 to 16 hours. CFPD was performed with two bedside-placed catheters. After initial filling, dialysate flow rate (100 ml/1.73 m2 per minute) was maintained with an adapted continuous venovenous hemofiltration machine. Ultrafiltration flow rate was set at 2.5 ml/1.73 m2 per minute. RESULTS: Mean ultrafiltration was 0.20 ml/1.73 m2 per minute with conventional PD versus 1.8 ml/1.73 m2 per minute with CFPD. Mean clearances of urea and creatinine were 5.0 and 7.6 ml/1.73 m2 per minute with conventional PD versus 15.0 and 28.8 ml/1.73 m2 per minute with CFPD, respectively. No complications occurred. CONCLUSIONS: In this first report of CFPD in six pediatric patients with acute renal failure, CFPD was on average three to five times more effective for urea and creatinine clearance and ultrafiltration than conventional PD, without any complications observed. CFPD has the ability to improve therapy for acute renal failure. PMID- 21030579 TI - Role of residual renal function in phosphate control and anemia management in chronic hemodialysis patients. AB - BACKGROUND AND OBJECTIVES: There is increasing awareness that residual renal function (RRF) has beneficial effects in hemodialysis (HD) patients. The aim of this study was to investigate the role of RRF, expressed as GFR, in phosphate and anemia management in chronic HD patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Baseline data of 552 consecutive patients from the Convective Transport Study (CONTRAST) were analyzed. Patients with a urinary output>=100 ml/24 h (n=295) were categorized in tertiles on the basis of degree of GFR and compared with anuric patients (i.e., urinary output<100 ml/24 h, n=274). Relations between GFR and serum phosphate and erythropoiesis-stimulating agent (ESA) index (weekly ESA dose per kg body weight divided by hematocrit) were analyzed with multivariable regression models. RESULTS: Phosphate levels were between 3.5 and 5.5 mg/dl in 68% of patients in the upper tertile (GFR>4.13 ml/min per 1.73 m2), as compared with 46% in anuric patients despite lower prescription of phosphate-binding agents. Mean hemoglobin levels were 11.9+/-1.2 g/dl with no differences between the GFR categories. The ESA index was 31% lower in patients in the upper tertile as compared with anuric patients. After adjustments for patient characteristics, patients in the upper tertile had significantly lower serum phosphate levels and ESA index as compared with anuric patients. CONCLUSIONS: This study suggests a strong relation between RRF and improved phosphate and anemia control in HD patients. Efforts to preserve RRF in HD patients could improve outcomes and should be encouraged. PMID- 21030580 TI - Effects of dietary phosphate and calcium intake on fibroblast growth factor-23. AB - BACKGROUND AND OBJECTIVES: Little is known about the influence of dietary phosphate intake on fibroblast growth factor-23 (FGF23) and its subsequent effects on vitamin D levels. This study addresses changes in intact FGF23 (iFGF23) and C-terminal FGF23 (cFGF23), phosphaturia, and levels of vitamin D on high and low phosphate and calcium intake. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Ten healthy subjects adhered to a diet low or high in phosphate and calcium content for 36 hours each with a 1-week interval during which subjects adhered to their usual diet. Serum phosphate, calcium, vitamin D metabolites, parathyroid hormone (PTH), and FGF23 levels (cFGF23 and iFGF23) were measured several times a day. Phosphate, calcium, and creatinine excretion was measured in 24-hour urine on all study days. RESULTS: Serum phosphate levels and urinary phosphate increased during high dietary phosphate intake (from 1.11 to 1.32 mmol/L, P<0.0001 and 21.6 to 28.8 mmol/d, P=0.0005, respectively). FGF23 serum levels increased during high dietary phosphate/calcium intake (cFGF23 from 60 to 72 RU/ml, P<0.001; iFGF23 from 33 to 37 ng/L, P=0.003), whereas PTH declined. 1,25-dihydroxyvitamin D (1,25D) showed an inverse relation with FGF23. CONCLUSIONS: Variation in dietary phosphate and calcium intake induces changes in FGF23 (on top of a circadian rhythm) and 1,25D blood levels as well as in urinary phosphate excretion. These changes are detectable the day after the change in the phosphate content of meals. Higher FGF23 levels are associated with phosphaturia and a decline in 1,25D levels. PMID- 21030581 TI - Access to kidney transplantation among the elderly in the United States: a glass half full, not half empty. AB - BACKGROUND AND OBJECTIVES: Few elderly ESRD patients are ever wait-listed for deceased-donor transplantation (DDTX), and waiting list outcomes may not reflect access to transplantation in this group. Our objective was to determine longitudinal changes in access to transplantation among all elderly patients with ESRD, not just those wait-listed for DDTX. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Using data from the US Renal Data System, we determined changes in the adjusted likelihood of transplantation from any donor source as an indicator of access to transplantation among all incident ESRD patients aged 60 to 75 years between 1995 and 2006. RESULTS: Access to transplantation doubled between 1995 and 2006 despite an apparent decrease in the likelihood of DDTX after wait listing. A threefold increase in the likelihood of living-donor transplantation, including a 1.5-fold increase in living-donor transplantation after wait-listing, was a key factor that led to increased access to transplantation. When a lead time bias related to the increased practice of placing patients on the waiting list before dialysis initiation in more recent years was accounted for, there was no decrease in the likelihood of DDTX after wait-listing. The likelihood of receiving a DDTX after placement on the waiting list was maintained by a threefold increase in expanded-criteria-donor transplantation and a 26% reduction in the risk for death on the waiting list. CONCLUSIONS: Although transplantation remains infrequent, elderly patients were twice as likely to undergo transplantation in 2006 versus 1995. Elderly patients with ESRD should not be dissuaded from pursuing transplantation. PMID- 21030582 TI - Kidney transplants for the elderly: hope or hype? PMID- 21030583 TI - The association between abnormal birth history and growth in children with CKD. AB - BACKGROUND AND OBJECTIVES: Poor linear growth is a well described complication of chronic kidney disease (CKD). This study evaluated whether abnormal birth history defined by low birth weight (LBW; <2500 g), prematurity (gestational age <36 weeks), small for gestational age (SGA; birth weight <10th percentile for gestational age), or intensive care unit (ICU) at birth were risk factors for poor growth outcomes in children with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Growth outcomes were quantified by age-sex-specific height and weight z-scores during 1393 visits from 426 participants of the Chronic Kidney Disease in Children Study, an observational cohort of children with CKD. Median baseline GFR was 42.9 ml/min per 1.73 m(2), 21% had a glomerular diagnosis, and 52% had CKD for >= 90% of their lifetime. RESULTS: A high prevalence of LBW (17%), SGA (14%), prematurity (12%), and ICU after delivery (40%) was observed. Multivariate analyses demonstrated a negative effect of LBW (-0.43 +/- 0.14; P < 0.01 for height and -0.37 +/- 0.16; P = 0.02 for weight) and of SGA (-0.29 +/- 0.16; P = 0.07 for height and -0.41 +/- 0.19; P = 0.03 for weight) on current height and weight. In children with glomerular versus nonglomerular diagnoses, the effect of SGA (-1.08 versus -0.18; P = 0.029) on attained weight was more pronounced in children with a glomerular diagnosis. CONCLUSIONS: LBW and SGA are novel risk factors for short stature and lower weight percentiles in children with mild to moderate CKD independent of kidney function. PMID- 21030584 TI - TDP2/TTRAP is the major 5'-tyrosyl DNA phosphodiesterase activity in vertebrate cells and is critical for cellular resistance to topoisomerase II-induced DNA damage. AB - Topoisomerase II (Top2) activity involves an intermediate in which the topoisomerase is covalently bound to a DNA double-strand break via a 5' phosphotyrosyl bond. Although these intermediates are normally transient, they can be stabilized by antitumor agents that act as Top2 "poisons," resulting in the induction of cytotoxic double-strand breaks, and they are implicated in the formation of site-specific translocations that are commonly associated with cancer. Recently, we revealed that TRAF and TNF receptor-associated protein (TTRAP) is a 5'-tyrosyl DNA phosphodiesterase (5'-TDP) that can cleave 5' phosphotyrosyl bonds, and we denoted this protein tyrosyl DNA phosphodiesterase-2 (TDP2). Here, we have generated TDP2-deleted DT40 cells, and we show that TDP2 is the major if not the only 5'-TDP activity present in vertebrate cells. We also show that TDP2-deleted DT40 cells are highly sensitive to the anticancer Top2 poison, etoposide, but are not hypersensitive to the Top1 poison camptothecin or the DNA-alkyating agent methyl methanesulfonate. These data identify an important mechanism for resistance to Top2-induced chromosome breakage and raise the possibility that TDP2 is a significant factor in cancer development and treatment. PMID- 21030585 TI - Adenosine-to-inosine RNA editing affects trafficking of the gamma-aminobutyric acid type A (GABA(A)) receptor. AB - Recoding by adenosine-to-inosine RNA editing plays an important role in diversifying proteins involved in neurotransmission. We have previously shown that the Gabra-3 transcript, coding for the alpha3 subunit of the GABA(A) receptor is edited in mouse, causing an isoleucine to methionine (I/M) change. Here we show that this editing event is evolutionarily conserved from human to chicken. Analyzing recombinant GABA(A) receptor subunits expressed in HEK293 cells, our results suggest that editing at the I/M site in alpha3 has functional consequences on receptor expression. We demonstrate that I/M editing reduces the cell surface and the total number of alpha3 subunits. The reduction in cell surface levels is independent of the subunit combination as it is observed for alpha3 in combination with either the beta2 or the beta3 subunit. Further, an amino acid substitution at the corresponding I/M site in the alpha1 subunit has a similar effect on cell surface presentation, indicating the importance of this site for receptor trafficking. We show that the I/M editing during brain development is inversely related to the alpha3 protein abundance. Our results suggest that editing controls trafficking of alpha3-containing receptors and may therefore facilitate the switch of subunit compositions during development as well as the subcellular distribution of alpha subunits in the adult brain. PMID- 21030586 TI - Liver X receptor (LXR) regulates human adipocyte lipolysis. AB - The Liver X receptor (LXR) is an important regulator of carbohydrate and lipid metabolism in humans and mice. We have recently shown that activation of LXR regulates cellular fuel utilization in adipocytes. In contrast, the role of LXR in human adipocyte lipolysis, the major function of human white fat cells, is not clear. In the present study, we stimulated in vitro differentiated human and murine adipocytes with the LXR agonist GW3965 and observed an increase in basal lipolysis. Microarray analysis of human adipocyte mRNA following LXR activation revealed an altered gene expression of several lipolysis-regulating proteins, which was also confirmed by quantitative real-time PCR. We show that expression and intracellular localization of perilipin1 (PLIN1) and hormone-sensitive lipase (HSL) are affected by GW3965. Although LXR activation does not influence phosphorylation status of HSL, HSL activity is required for the lipolytic effect of GW3965. This effect is abolished by PLIN1 knockdown. In addition, we demonstrate that upon activation, LXR binds to the proximal regions of the PLIN1 and HSL promoters. By selective knock-down of either LXR isoform, we show that LXRalpha is the major isoform mediating the lipolysis-related effects of LXR. In conclusion, the present study demonstrates that activation of LXRalpha up regulates basal human adipocyte lipolysis. This is at least partially mediated through LXR binding to the PLIN1 promoter and down-regulation of PLIN1 expression. PMID- 21030587 TI - Biosynthetic origin of the galactosamine substituent of Arabinogalactan in Mycobacterium tuberculosis. AB - The arabinogalactan (AG) of slow growing pathogenic Mycobacterium spp. is characterized by the presence of galactosamine (GalN) modifying some of the interior branched arabinosyl residues. The biosynthetic origin of this substituent and its role(s) in the physiology and/or pathogenicity of mycobacteria are not known. We report on the discovery of a polyprenyl-phospho-N acetylgalactosaminyl synthase (PpgS) and the glycosyltransferase Rv3779 from Mycobacterium tuberculosis required, respectively, for providing and transferring the GalN substrate for the modification of AG. Disruption of either ppgS (Rv3631) or Rv3779 totally abolished the synthesis of the GalN substituent of AG in M. tuberculosis H37Rv. Conversely, expression of ppgS in Mycobacterium smegmatis conferred upon this species otherwise devoid of ppgS ortholog and any detectable polyprenyl-phospho-N-acetylgalactosaminyl synthase activity the ability to synthesize polyprenyl-phospho-N-acetylgalactosamine (polyprenyl-P-GalNAc) from polyprenyl-P and UDP-GalNAc. Interestingly, this catalytic activity was increased 40-50-fold by co-expressing Rv3632, the encoding gene of a small membrane protein apparently co-transcribed with ppgS in M. tuberculosis H37Rv. The discovery of this novel lipid-linked sugar donor and the involvement of a the glycosyltransferase C-type glycosyltransferase in its transfer onto its final acceptor suggest that pathogenic mycobacteria modify AG on the periplasmic side of the plasma membrane. The availability of a ppgS knock-out mutant of M. tuberculosis provides unique opportunities to investigate the physiological function of the GalN substituent and the potential impact it may have on host pathogen interactions. PMID- 21030588 TI - Structural basis for c-KIT inhibition by the suppressor of cytokine signaling 6 (SOCS6) ubiquitin ligase. AB - The c-KIT receptor tyrosine kinase mediates the cellular response to stem cell factor (SCF). Whereas c-KIT activity is important for the proliferation of hematopoietic cells, melanocytes and germ cells, uncontrolled c-KIT activity contributes to the growth of diverse human tumors. Suppressor of cytokine signaling 6 (SOCS6) is a member of the SOCS family of E3 ubiquitin ligases that can interact with c-KIT and suppress c-KIT-dependent pathways. Here, we analyzed the molecular mechanisms that determine SOCS6 substrate recognition. Our results show that the SH2 domain of SOCS6 is essential for its interaction with c-KIT pY568. The 1.45-A crystal structure of SOCS6 SH2 domain bound to the c-KIT substrate peptide (c-KIT residues 564-574) revealed a highly complementary and specific interface giving rise to a high affinity interaction (K(d) = 0.3 MUm). Interestingly, the SH2 binding pocket extends to substrate residue position pY+6 and envelopes the c-KIT phosphopeptide with a large BG loop insertion that contributes significantly to substrate interaction. We demonstrate that SOCS6 has ubiquitin ligase activity toward c-KIT and regulates c-KIT protein turnover in cells. Our data support a role of SOCS6 as a feedback inhibitor of SCF-dependent signaling and provides molecular data to account for target specificity within the SOCS family of ubiquitin ligases. PMID- 21030589 TI - Benefits from unearthing "a biochemical Rosetta Stone". PMID- 21030591 TI - Natural and engineered photoactivated nucleotidyl cyclases for optogenetic applications. AB - Cyclic nucleotides, cAMP and cGMP, are ubiquitous second messengers that regulate metabolic and behavioral responses in diverse organisms. We describe purification, engineering, and characterization of photoactivated nucleotidyl cyclases that can be used to manipulate cAMP and cGMP levels in vivo. We identified the blaC gene encoding a putative photoactivated adenylyl cyclase in the Beggiatoa sp. PS genome. BlaC contains a BLUF domain involved in blue-light sensing using FAD and a nucleotidyl cyclase domain. The blaC gene was overexpressed in Escherichia coli, and its product was purified. Irradiation of BlaC in vitro resulted in a small red shift in flavin absorbance, typical of BLUF photoreceptors. BlaC had adenylyl cyclase activity that was negligible in the dark and up-regulated by light by 2 orders of magnitude. To convert BlaC into a guanylyl cyclase, we constructed a model of the nucleotidyl cyclase domain and mutagenized several residues predicted to be involved in substrate binding. One triple mutant, designated BlgC, was found to have photoactivated guanylyl cyclase in vitro. Irradiation with blue light of the E. coli cya mutant expressing BlaC or BlgC resulted in the significant increases in cAMP or cGMP synthesis, respectively. BlaC, but not BlgC, restored cAMP-dependent growth of the mutant in the presence of light. Small protein sizes, negligible activities in the dark, high light-to-dark activation ratios, functionality at broad temperature range and physiological pH, as well as utilization of the naturally occurring flavins as chromophores make BlaC and BlgC attractive for optogenetic applications in various animal and microbial models. PMID- 21030590 TI - pH-dependent studies reveal an efficient hydroxylation mechanism of the oxygenase component of p-hydroxyphenylacetate 3-hydroxylase. AB - p-Hydroxyphenylacetate (HPA) 3-hydroxylase (HPAH) catalyzes the hydroxylation of HPA at the ortho-position to yield 3,4-dihydroxyphenylacetate. The enzyme is a flavin-dependent two-component monooxygenase that consists of a reductase component and an oxygenase component (C(2)). C(2) catalyzes the hydroxylation of HPA using oxygen and reduced FMN as co-substrates. To date, the effects of pH on the oxygenation of the two-component monooxygenases have never been reported. Here, we report the reaction kinetics of C(2).FMNH(-) with oxygen at various pH values investigated by stopped-flow and rapid quenched-flow techniques. In the absence of HPA, the rate constant for the formation of C4a-hydroperoxy-FMN (~1.1 * 10(6) m(-1)s(-1)) was unaffected at pH 6.2-9.9, which indicated that the pK(a) of the enzyme-bound reduced FMN was less than 6.2. The rate constant for the following H(2)O(2) elimination step increased with higher pH, which is consistent with a pK(a) of >9.4. In the presence of HPA, the rate constants for the formation of C4a-hydroperoxy-FMN (~4.8 * 10(4) m(-1)s(-1)) and the ensuing hydroxylation step (15-17 s(-1)) were not significantly affected by the pH. In contrast, the following steps of C4a-hydroxy-FMN dehydration to form oxidized FMN occurred through two pathways that were dependent on the pH of the reaction. One pathway, dominant at low pH, allowed the detection of a C4a-hydroxy-FMN intermediate, whereas the pathway dominant at high pH produced oxidized FMN without an apparent accumulation of the intermediate. However, both pathways efficiently catalyzed hydroxylation without generating significant amounts of wasteful H(2)O(2) at pH 6.2-9.9. The decreased accumulation of the intermediate at higher pH was due to the greater rates of C4a-hydroxy-FMN decay caused by the abolishment of substrate inhibition in the dehydration step at high pH. PMID- 21030592 TI - Dopamine D(3) receptors are down-regulated following heterologous endocytosis by a specific interaction with G protein-coupled receptor-associated sorting protein 1. AB - The D(3) dopamine receptor is endocytosed through a heterologous mechanism mediated by phorbol esters. Here, we show that following this endocytosis the D(3) dopamine receptors fail to recycle and are instead targeted for degradation through an interaction with the G protein-coupled receptor (GPCR)-associated sorting protein-1 (GASP-1). Furthermore, we identified a specific binding motif in the C terminus common to the D(3) and D(2) that confers GASP-1 binding. shRNA knockdown of GASP-1 delayed post-endocytic degradation of both the D(2) and D(3) dopamine receptors. In addition, mutation of the D(2) and D(3) receptor C termini to resemble the D(4), which does not interact with GASP-1, not only inhibited GASP-1 binding but slowed degradation after endocytosis. Conversely, mutation of the C terminus of the D(4) to resemble that of the D(2) and D(3) facilitated GASP 1 binding and promoted post-endocytic degradation of the mutant D(4) receptor. Thus, we have identified a motif that is both necessary and sufficient to promote GASP-1 binding and receptor degradation. In addition, these data demonstrated that GASP-1 can mediate post-endocytic degradation of dopamine receptors that have been endocytosed not only as a consequence of dopamine activation but also as a consequence of activation by phorbol esters. PMID- 21030593 TI - Characterization of promoter elements regulating the expression of the human neurotensin/neuromedin N gene. AB - Expression of the gene encoding neurotensin/neuromedin N (NT/N) is mostly limited to the brain and specialized enteroendocrine N cells in the distal small intestine. We have identified key regulatory elements in the promoter region that are involved in human NT/N (hNT/N) gene expression in the novel human endocrine cell line, BON, which resembles intestinal N cells in several important aspects including NT/N precursor protein processing, ratios of different NT/N mRNA isoforms, and high levels of constitutive expression of the NT/N gene. In this study, we demonstrated multiple cis-regulatory elements including a proximal region containing a cAMP-responsive element (CRE)/AP-1-like element that binds both the AP-1 and CRE-binding protein (CREB)/ATF proteins (c-Jun, ATF-1, ATF-2, JunD, and CREB). Similar to the rat NT/N gene, this region is critical for constitutive hNT/N gene expression. Moreover, we identified a novel region that binds the orphan hormone receptor, NR2F2. We have demonstrated that the C terminus of NR2F2 strongly represses hNT/N transcription, whereas an N-terminal domain antagonizes this repressive effect. Regulation of NT/N expression by NR2F2 may have important consequences for lipid metabolism. We speculate that a complex interplay between the proximal CRE/AP-1-like motif and NR2F2 binding region exists to regulate hNT/N expression, which is critical for the high level of constitutive expression of NT/N in enteroendocrine cells. Finally, the BON cell line provides a unique model to characterize the factors regulating expression of the hNT/N gene and to better understand the mechanisms responsible for terminal differentiation of the N cell lineage in the gut. PMID- 21030594 TI - Light modulation of cellular cAMP by a small bacterial photoactivated adenylyl cyclase, bPAC, of the soil bacterium Beggiatoa. AB - The recent success of channelrhodopsin in optogenetics has also caused increasing interest in enzymes that are directly activated by light. We have identified in the genome of the bacterium Beggiatoa a DNA sequence encoding an adenylyl cyclase directly linked to a BLUF (blue light receptor using FAD) type light sensor domain. In Escherichia coli and Xenopus oocytes, this photoactivated adenylyl cyclase (bPAC) showed cyclase activity that is low in darkness but increased 300 fold in the light. This enzymatic activity decays thermally within 20 s in parallel with the red-shifted BLUF photointermediate. bPAC is well expressed in pyramidal neurons and, in combination with cyclic nucleotide gated channels, causes efficient light-induced depolarization. In the Drosophila central nervous system, bPAC mediates light-dependent cAMP increase and behavioral changes in freely moving animals. bPAC seems a perfect optogenetic tool for light modulation of cAMP in neuronal cells and tissues and for studying cAMP-dependent processes in live animals. PMID- 21030595 TI - HDAC3 is negatively regulated by the nuclear protein DBC1. AB - HDAC3 is a member of the class I histone deacetylase family that regulates gene expression by deacetylation of histones and non-histone proteins. HDAC3 activity has been shown to be modulated by interaction with the co-repressors NCoR and SMRT. Here, we present evidence that the nuclear protein DBC1 is an endogenous inhibitor of HDAC3. DBC1 has been previously identified as a regulator of some nuclear receptors, the methyltransferase SUV39H1, and the NAD-dependent deacetylase SIRT1. Furthermore, DBC1 has been shown to influence transcription regulation and apoptosis, and it may also act as a tumor suppressor. We found that DBC1 interacts and specifically inhibits the deacetylase HDAC3. This interaction depends on the N terminus of DBC1 and the C terminus of HDAC3. Expression of DBC1 not only inhibited HDAC3 activity but also altered its subcellular distribution. In addition, knockdown of endogenous DBC1 in cells and knock-out in mouse tissues increased HDAC3 deacetylase activity. Together, these results identify DBC1 as a new regulator of HDAC3 and demonstrate that DBC1 is a negative regulator of two key distinct deacetylases, SIRT1 and HDAC3. These findings may lead to a better understanding of the biological roles of DBC1 and HDAC3 in metabolic diseases and cancer. PMID- 21030596 TI - Crystal structure of HugZ, a novel heme oxygenase from Helicobacter pylori. AB - The crystal structure of a heme oxygenase (HO) HugZ from Helicobacter pylori complexed with heme has been solved and refined at 1.8 A resolution. HugZ is part of the iron acquisition mechanism of H. pylori, a major pathogen of human gastroenteric diseases. It is required for the adaptive colonization of H. pylori in hosts. Here, we report that HugZ is distinct from all other characterized HOs. It exists as a dimer in solution and in crystals, and the dimer adopts a split barrel fold that is often found in FMN-binding proteins but has not been observed in hemoproteins. The heme is located at the intermonomer interface and is bound by both monomers. The heme iron is coordinated by the side chain of His(245) and an azide molecule when it is present in crystallization conditions. Experiments show that Arg(166), which is involved in azide binding, is essential for HugZ enzymatic activity, whereas His(245), surprisingly, is not, implying that HugZ has an enzymatic mechanism distinct from other HOs. The placement of the azide corroborates the observed gamma-meso specificity for the heme degradation reaction, in contrast to most known HOs that have alpha-meso specificity. We demonstrate through sequence and structural comparisons that HugZ belongs to a new heme-binding protein family with a split-barrel fold. Members of this family are widespread in pathogenic bacteria and may play important roles in the iron acquisition of these bacteria. PMID- 21030597 TI - Magnesium modulates ROMK channel-mediated potassium secretion. AB - The ability of intracellular and extracellular Mg(2+) to block secretory K(+) currents through ROMK channels under physiologic conditions is incompletely understood. We expressed ROMK2 channels in Xenopus oocytes and measured unitary currents in the inside-out and cell-attached modes of the patch-clamp technique. With 110 mM K(+) on both sides of the membrane, 0.2 to 5 mM Mg(2+) on the cytoplasmic side reduced outward currents, but not inward currents, at V(m) > 0. With 11 or 1.1 mM extracellular K(+) ([K(+)](o)), >=0.2 mM Mg(2+) blocked outward currents in the physiologic V(m) range (0 to -60 mV). With decreasing [K(+)](o), the apparent dissociation constant of the blocker decreased, but the voltage dependence of block did not significantly change. Whole-cell recordings from principal cells of rat cortical collecting ducts revealed similar inhibitory effects of intracellular Mg(2+). Mg(2+) added to the extracellular solution also reduced single-channel currents with an affinity that increased as [K(+)](o) decreased. In conclusion, physiologic concentrations of intracellular and extracellular Mg(2+) can influence secretory K(+) currents through ROMK channels. These effects could play a role in the modulation of K(+) transport under conditions of K(+) and/or Mg(2+) depletion. PMID- 21030598 TI - Minocycline prevents osmotic demyelination syndrome by inhibiting the activation of microglia. AB - Rapid correction of chronic hyponatremia can lead to osmotic demyelination syndrome (ODS), a severe demyelination disease. The microglia that accumulate in the demyelinative lesions may play a detrimental role in the pathogenesis of ODS by producing proinflammatory cytokines, suggesting that they may be a target for therapeutic intervention. Here, we investigated whether minocycline, a selective and potent inhibitor of microglial activation, could protect against ODS in rats. We induced hyponatremia by liquid diet feeding and dDAVP infusion. Rapid correction of the hyponatremia 7 days later resulted in neurologic impairment with severe demyelinative lesions. Activated microglia accumulated at the site of demyelination. Treatment with minocycline within 24 hours of rapid correction, however, was protective: rats exhibited minimal neurologic impairment, and survival improved. Histologic analysis showed that minocycline inhibited demyelination and suppressed the accumulation of microglia at the site of demyelination. Real-time RT-PCR and immunohistochemical analyses showed that minocycline inhibited the activity of microglia and the expression of inflammatory cytokines (e.g. IL-1beta, inducible nitric-oxide synthase, and TNF alpha), monocyte chemoattractant protein-1, and matrix metalloproteinase-12 in microglia. These results demonstrate that minocycline can protect against ODS by inhibiting the activation and accumulation of microglia at the site of demyelinative lesions, suggesting its possible use in clinical practice. PMID- 21030599 TI - Imaging of the porous ultrastructure of the glomerular epithelial filtration slit. AB - The ultrastructure of the glomerular filtration slit is still controversial. In the last 30 years, observations from transmission electron microscopy (TEM) and theoretical analysis of solute clearance produced conflicting results. Here, we used scanning EM with a high-sensitivity detector to image the deepest regions of the filtration slits and report a previously undescribed organization of the slits' ultrastructure. In contrast to previous TEM imaging, we observed circular and ellipsoidal pores in the podocyte junctions mainly located in the central region of the slit diaphragm. The normal mean pore radius estimated by digital morphometric analysis had a log-normal distribution, with an average value of 12.1 nm. In proteinuric pathologic conditions, the mean pore radius values were also log-normally distributed with the presence of some very large pores, exceeding the sizes observed in normal conditions. Our morphologic analysis suggests that the filtration slit is a heteroporous structure instead of the previously proposed zipper-like structure. Selective changes in the ultrastructural organization of the pores may be responsible for the increased filtration of plasma proteins in glomerular disease. PMID- 21030600 TI - Blockade of Wnt/beta-catenin signaling by paricalcitol ameliorates proteinuria and kidney injury. AB - Recent studies implicate Wnt/beta-catenin signaling in podocyte dysfunction. Because vitamin D analogs can inhibit beta-catenin in other tissues, we tested whether the vitamin D analog paricalcitol could ameliorate podocyte injury, proteinuria, and renal fibrosis in adriamycin (ADR) nephropathy. Compared with vehicle-treated controls, paricalcitol preserved expression of nephrin, podocin, and WT1; prevented proteinuria; and reduced glomerulosclerotic lesions induced by ADR. Paricalcitol also inhibited expression of proinflammatory cytokines, reduced renal infiltration of monocytes/macrophages, hampered activation of renal myofibroblasts, and suppressed expression of the fibrogenic TGF-beta1, CTGF, fibronectin, and types I and III collagen. Selective suppression of renal Wnt4, Wnt7a, Wnt7b, and Wnt10a expression after ADR accompanied these renoprotective effects of paricalcitol. Significant upregulation of beta-catenin, predominantly in podocytes and tubular epithelial cells, accompanied renal injury; paricalcitol largely abolished this induction of renal beta-catenin and inhibited renal expression of Snail, a downstream effector of Wnt/beta-catenin signaling. Administration of paricalcitol also ameliorated established proteinuria. In vitro, paricalcitol induced a physical interaction between the vitamin D receptor and beta-catenin in podocytes, which led to suppression of beta-catenin-mediated gene transcription. In summary, these findings suggest that paricalcitol prevents podocyte dysfunction, proteinuria, and kidney injury in adriamycin nephropathy by inhibiting Wnt/beta-catenin signaling. PMID- 21030601 TI - Uncovering genes and regulatory pathways related to urinary albumin excretion. AB - Identifying the genes underlying quantitative trait loci (QTL) for disease is difficult, mainly because of the low resolution of the approach and the complex genetics involved. However, recent advances in bioinformatics and the availability of genetic resources now make it possible to narrow the genetic intervals, test candidate genes, and define pathways affected by these QTL. In this study, we mapped three significant QTL and one suggestive QTL for an increased albumin-to-creatinine ratio on chromosomes (Chrs) 1, 4, 15, and 17, respectively, in a cross between the inbred MRL/MpJ and SM/J strains of mice. By combining data from several sources and by utilizing gene expression data, we identified Tlr12 as a likely candidate for the Chr 4 QTL. Through the mapping of 33,881 transcripts measured by microarray on kidney RNA from each of the 173 male F2 animals, we identified several downstream pathways associated with these QTL, including the glycan degradation, leukocyte migration, and antigen-presenting pathways. We demonstrate that by combining data from multiple sources, we can identify not only genes that are likely to be causal candidates for QTL but also the pathways through which these genes act to alter phenotypes. This combined approach provides valuable insights into the causes and consequences of renal disease. PMID- 21030602 TI - Body mass index, hormone replacement therapy, and endometrial cancer risk: a meta analysis. AB - BACKGROUND: Body mass index (BMI) is a risk factor for endometrial cancer. We quantified the risk and investigated whether the association differed by use of hormone replacement therapy (HRT), menopausal status, and histologic type. METHODS: We searched MEDLINE and EMBASE (1966 to December 2009) to identify prospective studies of BMI and incident endometrial cancer. We did random-effects meta-analyses, meta-regressions, and generalized least square regressions for trend estimations assuming linear, and piecewise linear, relationships. RESULTS: Twenty-four studies (17,710 cases) were analyzed; 9 studies contributed to analyses by HRT, menopausal status, or histologic type, all published since 2003. In the linear model, the overall risk ratio (RR) per 5 kg/m(2) increase in BMI was 1.60 (95% CI, 1.52-1.68), P < 0.0001. In the piecewise model, RRs compared with a normal BMI were 1.22 (1.19-1.24), 2.09 (1.94-2.26), 4.36 (3.75-5.10), and 9.11 (7.26-11.51) for BMIs of 27, 32, 37, and 42 kg/m(2), respectively. The association was stronger in never HRT users than in ever users: RRs were 1.90 (1.57-2.31) and 1.18 (95% CI, 1.06-1.31) with P for interaction = 0.003. In the piecewise model, the RR in never users was 20.70 (8.28-51.84) at BMI 42 kg/m(2), compared with never users at normal BMI. The association was not affected by menopausal status (P = 0.34) or histologic type (P = 0.26). CONCLUSIONS: HRT use modifies the BMI-endometrial cancer risk association. IMPACT: These findings support the hypothesis that hyperestrogenia is an important mechanism underlying the BMI-endometrial cancer association, whilst the presence of residual risk in HRT users points to the role of additional systems. PMID- 21030603 TI - Ordered subset analysis identifies loci influencing lung cancer risk on chromosomes 6q and 12q. AB - BACKGROUND: Genetic susceptibility for cancer can differ substantially among families. We use trait-related covariates to identify a genetically homogeneous subset of families with the best evidence for linkage in the presence of heterogeneity. METHODS: We performed a genome-wide linkage screen in 93 families. Samples and data were collected by the familial lung cancer recruitment sites of the Genetic Epidemiology of Lung Cancer Consortium. We estimated linkage scores for each family by the Markov chain Monte Carlo procedure using SimWalk2 software. We used ordered subset analysis (OSA) to identify genetically homogenous families by ordering families based on a disease-associated covariate. We performed permutation tests to determine the relationship between the trait related covariate and the evidence for linkage. RESULTS: A genome-wide screen for lung cancer loci identified strong evidence for linkage to 6q23-25 and suggestive evidence for linkage to 12q24 using OSA, with peak logarithm of odds (LOD) scores of 4.19 and 2.79, respectively. We found other chromosomes also suggestive for linkages, including 5q31-q33, 14q11, and 16q24. CONCLUSIONS: Our OSA results support 6q as a lung cancer susceptibility locus and provide evidence for disease linkage on 12q24. This study further increased our understanding of the inheritability for lung cancer. Validation studies using larger sample size are needed to verify the presence of several other chromosomal regions suggestive of an increased risk for lung cancer and/or other cancers. IMPACT: OSA can reduce genetic heterogeneity in linkage study and may assist in revealing novel susceptibility loci. PMID- 21030604 TI - Calcium-permeable AMPA receptor dynamics mediate fear memory erasure. AB - Traumatic fear memories can be inhibited by behavioral therapy for humans, or by extinction training in rodent models, but are prone to recur. Under some conditions, however, these treatments generate a permanent effect on behavior, which suggests that emotional memory erasure has occurred. The neural basis for such disparate outcomes is unknown. We found that a central component of extinction-induced erasure is the synaptic removal of calcium-permeable alpha amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors (AMPARs) in the lateral amygdala. A transient up-regulation of this form of plasticity, which involves phosphorylation of the glutamate receptor 1 subunit of the AMPA receptor, defines a temporal window in which fear memory can be degraded by behavioral experience. These results reveal a molecular mechanism for fear erasure and the relative instability of recent memory. PMID- 21030605 TI - PML regulates apoptosis at endoplasmic reticulum by modulating calcium release. AB - The promyelocytic leukemia (PML) tumor suppressor is a pleiotropic modulator of apoptosis. However, the molecular basis for such a diverse proapoptotic role is currently unknown. We show that extranuclear Pml was specifically enriched at the endoplasmic reticulum (ER) and at the mitochondria-associated membranes, signaling domains involved in ER-to-mitochondria calcium ion (Ca(2+)) transport and in induction of apoptosis. We found Pml in complexes of large molecular size with the inositol 1,4,5-trisphosphate receptor (IP(3)R), protein kinase Akt, and protein phosphatase 2a (PP2a). Pml was essential for Akt- and PP2a-dependent modulation of IP(3)R phosphorylation and in turn for IP(3)R-mediated Ca(2+) release from ER. Our findings provide a mechanistic explanation for the pleiotropic role of Pml in apoptosis and identify a pharmacological target for the modulation of Ca(2+) signals. PMID- 21030606 TI - Probing the ultimate limit of fiber-optic strain sensing. AB - The measurement of relative displacements and deformations is important in many fields such as structural engineering, aerospace, geophysics, and nanotechnology. Optical-fiber sensors have become key tools for strain measurements, with sensitivity limits ranging between 10(-9) and 10(-6)epsilon hertz (Hz)(-1/2) (where epsilon is the fractional length change). We report on strain measurements at the 10(-13)epsilon-Hz(-1/2) level using a fiber Bragg-grating resonator with a diode-laser source that is stabilized against a quartz-disciplined optical frequency comb, thus approaching detection limits set by thermodynamic phase fluctuations in the fiber. This scheme may provide a route to a new generation of strain sensors that is entirely based on fiber-optic systems, which are aimed at measuring fundamental physical quantities; for example, in gyroscopes, accelerometers, and gravity experiments. PMID- 21030608 TI - Effect of adjuvant-induced systemic inflammation in rats on hepatic disposition kinetics of taurocholate. AB - It has been reported that the adjuvant-induced inflammation could affect drug metabolism in liver. Here we further investigated the effect of inflammation on drug transport in liver using taurocholate as a model drug. The hepatic disposition kinetics of [(3)H]taurocholate in perfused normal and adjuvant treated rat livers were investigated by the multiple indicator dilution technique and data were analyzed by a previously reported hepatobiliary taurocholate transport model. Real-time RT-PCR was also performed to determine the mRNA expression of liver bile salt transporters in normal and diseased livers. The uptake and biliary excretion of taurocholate were impaired in the adjuvant treated rats as shown by decreased influx rate constant k(in) (0.65 +/- 0.09 vs. 2.12 +/- 0.30) and elimination rate constant k(be) (0.09 +/- 0.02 vs. 0.17 +/- 0.04) compared with control rat group, whereas the efflux rate constant k(out) was greatly increased (0.07 +/- 0.02 vs. 0.02 +/- 0.01). The changes of mRNA expression of liver bile salt transporters were found in adjuvant-treated rats. Hepatic taurocholate extraction ratio in adjuvant-treated rats (0.86 +/- 0.05, n = 6) was significantly reduced compared with 0.93 +/- 0.05 (n = 6) in normal rats. Hepatic extraction was well correlated with altered hepatic ATP content (r(2) = 0.90). In conclusion, systemic inflammation greatly affects hepatic ATP content/production and associated transporter activities and causes an impairment of transporter-mediated solute trafficking and pharmacokinetics. PMID- 21030607 TI - Physiological relevance of cell-specific distribution patterns of CFTR, NKCC1, NBCe1, and NHE3 along the crypt-villus axis in the intestine. AB - We examined the cell-specific subcellular expression patterns for sodium- and potassium-coupled chloride (NaK2Cl) cotransporter 1 (NKCC1), Na(+) bicarbonate cotransporter (NBCe1), cystic fibrosis transmembrane conductance regulator (CFTR), and Na(+)/H(+) exchanger 3 (NHE3) to understand the functional plasticity and synchronization of ion transport functions along the crypt-villus axis and its relevance to intestinal disease. In the unstimulated intestine, all small intestinal villus enterocytes coexpressed apical CFTR and NHE3, basolateral NBCe1, and mostly intracellular NKCC1. All (crypt and villus) goblet cells strongly expressed basolateral NKCC1 (at approximately three-fold higher levels than villus enterocytes), but no CFTR, NBCe1, or NHE3. Lower crypt cells coexpressed apical CFTR and basolateral NKCC1, but no NHE3 or NBCe1 (except NBCe1 expressing proximal colonic crypts). CFTR, NBCe1, and NKCC1 colocalized with markers of early and recycling endosomes, implicating endocytic recycling in cell specific anion transport. Brunner's glands of the proximal duodenum coexpressed high levels of apical/subapical CFTR and basolateral NKCC1, but very low levels of NBCe1, consistent with secretion of Cl(-)-enriched fluid into the crypt. The cholinergic agonist carbachol rapidly (within 10 min) reduced cell volume along the entire crypt/villus axis and promoted NHE3 internalization into early endosomes. In contrast, carbachol induced membrane recruitment of NKCC1 and CFTR in all crypt and villus enterocytes, NKCC1 in all goblet cells, and NBCe1 in all villus enterocytes. These observations support regulated vesicle traffic in Cl(-) secretion by goblet cells and Cl(-) and HCO(3)(-) secretion by villus enterocytes during the transient phase of cholinergic stimulation. Overall, the carbachol induced membrane trafficking profile of the four ion transporters supports functional plasticity of the small intestinal villus epithelium that enables it to conduct both absorptive and secretory functions. PMID- 21030609 TI - Apical Na+-D-glucose cotransporter 1 (SGLT1) activity and protein abundance are expressed along the jejunal crypt-villus axis in the neonatal pig. AB - Gut apical Na(+)-glucose cotransporter 1 (SGLT1) activity is high at the birth and during suckling, thus contributing substantially to neonatal glucose homeostasis. We hypothesize that neonates possess high SGLT1 maximal activity by expressing apical SGLT1 protein along the intestinal crypt-villus axis via unique control mechanisms. Kinetics of SGLT1 activity in apical membrane vesicles, prepared from epithelial cells sequentially isolated along the jejunal crypt villus axis from neonatal piglets by the distended intestinal sac method, were measured. High levels of maximal SGLT1 uptake activity were shown to exist along the jejunal crypt-villus axis in the piglets. Real-time RT-PCR analyses showed that SGLT1 mRNA abundance was lower (P < 0.05) by 30-35% in crypt cells than in villus cells. There were no significant differences in SGLT1 protein abundances on the jejunal apical membrane among upper villus, middle villus, and crypt cells, consistent with the immunohistochemical staining pattern. Higher abundances (P < 0.05) of total eukaryotic initiation factor 4E (eIF4E) protein and eIE4E-binding protein 1 gamma-isoform in contrast to a lower (P < 0.05) abundance of phosphorylated (Pi) eukaryotic elongation factor 2 (eEF2) protein and the eEF2-Pi to total eEF2 abundance ratio suggest higher global protein translational efficiency in the crypt cells than in the upper villus cells. In conclusion, neonates have high intestinal apical SGLT1 uptake activity by abundantly expressing SGLT1 protein in the epithelia and on the apical membrane along the entire crypt-villus axis in association with enhanced protein translational control mechanisms in the crypt cells. PMID- 21030610 TI - MicroRNA-92b regulates expression of the oligopeptide transporter PepT1 in intestinal epithelial cells. AB - MicroRNAs (miRNAs), which are noncoding RNAs that posttranscriptionally inhibit expression of target genes, have recently emerged as important regulators of many cellular functions such as cell differentiation. The epithelial di/tripeptide membrane transporter PepT1 is expressed in highly differentiated cells (the villous tip) but not in undifferentiated cells (the crypt) of the small intestine. Here, we investigated the regulation of PepT1 expression by miRNAs and its functional consequences. We observed a reverse correlation between the expression levels of PepT1 and mature miRNA-92b (miR-92b) during the differentiation of intestinal epithelial Caco2-BBE cells, suggesting a miR-92b mediated regulation of PepT1 expression. We demonstrate that miR-92b suppressed PepT1 expression at both mRNA and protein levels, with subsequent reduced PepT1 transport activity, in Caco2-BBE cells by directly targeting the PepT1 3' untranslated region. In addition, miR-92b suppresses bacterial peptide-induced proinflammatory responses in intestinal epithelial cells by inhibiting PepT1 expression. Altogether, our study provides for the first time evidence for the regulation of PepT1 expression at a posttranscriptional level by miRNAs in intestinal epithelial cells during pathophysiological states. PMID- 21030612 TI - Monosodium glutamate raises antral distension and plasma amino acid after a standard meal in humans. AB - The consumption of monosodium glutamate (MSG) is advocated to elicit physiological and metabolic effects, yet these effects have been poorly investigated directly in humans and in particular in the postprandial phase. Thirteen healthy adults were supplemented for 6 days with a nutritional dose of MSG (2 g) or sodium chloride (NaCl) as control, following a crossover design. On the 7th day, they underwent a complete postprandial examination for the 6 h following the ingestion of the same liquid standard meal (700 kcal, 20% of energy as [(15)N]protein, 50% as carbohydrate, and 30% as fat) supplemented with MSG or NaCl. Real-ultrasound measures of antral area indicated a significant increased distension for the 2 h following the meal supplemented with MSG vs. NaCl. This early postprandial phase was also associated with significantly increased levels of circulating leucine, isoleucine, valine, lysine, cysteine, alanine, tyrosine, and tryptophan after MSG compared with NaCl. No changes to the postprandial glucose, insulin, glucagon-like peptide (GLP)-1, and ghrelin were noted between MSG- and NaCl-supplemented meals. Subjective assessments of hunger and fullness were neither affected by MSG supplementation. Finally, the postprandial fate of dietary N was identical between dietary conditions. Our findings indicate that nutritional dose of MSG promoted greater postprandial elevations of several indispensable amino acids in plasma and induced gastric distension. Further work to elucidate the possible sparing effect of MSG on indispensable amino acid first pass uptake in humans is warranted. This trial was registered at clinicaltrials.gov as NCT00862017. PMID- 21030613 TI - Driving U.S. energy leadership. PMID- 21030611 TI - Role of liver sinusoidal endothelial cells and stabilins in elimination of oxidized low-density lipoproteins. AB - Atherogenesis is associated with elevated levels of low-density lipoprotein (LDL) and its oxidized form (oxLDL) in the blood. The liver is an important scavenger organ for circulating oxLDLs. The present study aimed to examine endocytosis of mildly oxLDL (the major circulating form of oxLDLs) in liver sinusoidal endothelial cells (LSECs) and the involvement of the scavenger receptors stabilin 1 and stabilin-2 in this process. Freshly isolated LSECs, Kupffer cells (KCs), and stabilin-1- and stabilin-2-transfected human embryonic kidney cells were incubated with fluorescently labeled or radiolabeled oxLDLs [oxidized for 3 h (oxLDL(3)), 6 h, or 24 h (oxLDL(24))] to measure endocytosis. The intracellular localization of oxLDLs and stabilins in LSECs was examined by immunofluorescence and immunogold electron microscopy. Whereas oxLDL(24) was endocytosed both by LSECs and KCs, oxLDL(3) (mildly oxLDL) was taken up by LSECs only. The LSEC uptake of oxLDLs was significantly inhibited by the scavenger receptor ligand formaldehyde-treated serum albumin. Uptake of all modified LDLs was high in stabilin-1-transfected cells, whereas stabilin-2-transfected cells preferentially took up oxLDL(24), suggesting that stabilin-1 is a more important receptor for mildly oxLDLs than stabilin-2. Double immunogold labeling experiments in LSECs indicated interactions of stabilin-1 and stabilin-2 with oxLDL(3) on the cell surface, in coated pits, and endocytic vesicles. LSECs but not KCs endocytosed mildly oxLDL. Both stabilin-1 and stabilin-2 were involved in the LSEC endocytosis of oxLDLs, but experiments with stabilin-transfected cells pointed to stabilin-1 as the most important receptor for mildly oxLDL. PMID- 21030614 TI - Research funding. Campaign for U.K. science helps deflect budget ax. PMID- 21030615 TI - Planetary science. Liquid water found on Mars, but it's still a hard road for life. PMID- 21030616 TI - Newsmaker interview: Carl Wieman. Nobelist 'coach' takes on U.S. science education. Interview by Jeffrey Mervis. PMID- 21030618 TI - Genomics. 1000 Genomes Project gives new map of genetic diversity. PMID- 21030619 TI - Iraq War. Leaked documents provide bonanza for researchers. PMID- 21030620 TI - Epigenetic drugs take on cancer. PMID- 21030621 TI - Genes link epigenetics and cancer. PMID- 21030622 TI - Pharmacogenomics. Gene variants affect hepatitis C treatment, but link is elusive. PMID- 21030623 TI - U.S. science education. Data say retention is better answer to 'shortage' than recruitment. PMID- 21030624 TI - What's in a number? PMID- 21030625 TI - Society of Vertebrate Paleontology. Going back to the future to understand climate change. PMID- 21030626 TI - Society of Vertebrate Paleontology. When rodents marched into Paris. PMID- 21030627 TI - Society of Vertebrate Paleontology. Snapshots from the meeting. PMID- 21030628 TI - Asian water towers: more on monsoons. PMID- 21030630 TI - The best test of Ph.D. student success. PMID- 21030629 TI - Mass fruiting in Borneo: a missed opportunity. PMID- 21030633 TI - Research funding. Sustaining the data and bioresource commons. PMID- 21030634 TI - Immunology. Innate lymphoid cell relations. PMID- 21030635 TI - Chemistry. Caging carbon dioxide. PMID- 21030636 TI - Cell biology. Forced to be unequal. PMID- 21030637 TI - Stem cells. Epigenome disruptors. PMID- 21030638 TI - Chemistry. A little chemistry helps the big get bigger. PMID- 21030639 TI - Structural biology. The Tao of chloride transporter structure. PMID- 21030640 TI - Immunology. Infection protection and natural selection. PMID- 21030641 TI - Retrospective. Georges Charpak (1924-2010). PMID- 21030642 TI - SPORE series winner. Physical phenomena in real time. PMID- 21030643 TI - Epigenetics. What is epigenetics? Introduction. PMID- 21030644 TI - Molecular signals of epigenetic states. AB - Epigenetic signals are responsible for the establishment, maintenance, and reversal of metastable transcriptional states that are fundamental for the cell's ability to "remember" past events, such as changes in the external environment or developmental cues. Complex epigenetic states are orchestrated by several converging and reinforcing signals, including transcription factors, noncoding RNAs, DNA methylation, and histone modifications. Although all of these pathways modulate transcription from chromatin in vivo, the mechanisms by which epigenetic information is transmitted through cell division remain unclear. Because epigenetic states are metastable and change in response to the appropriate signals, a deeper understanding of their molecular framework will allow us to tackle the dysregulation of epigenetics in disease. PMID- 21030645 TI - A small-RNA perspective on gametogenesis, fertilization, and early zygotic development. AB - Transient populations of cis- and trans-acting small RNAs have recently emerged as key regulators of extensive epigenetic changes taking place during periconception, which encompasses gametogenesis, fertilization, and early zygotic development. These small RNAs are not only important to maintain genome integrity in the gametes and zygote, but they also actively contribute to assessing the compatibility of parental genomes at fertilization and to promoting long-term memory of the zygotic epigenetic landscape by affecting chromatin. Striking parallels exist in the biogenesis and modus operandi of these molecules among diverse taxa, unraveling universal themes of small-RNA-mediated epigenetic reprogramming during sexual reproduction. PMID- 21030646 TI - Epigenetic reprogramming in plant and animal development. AB - Epigenetic modifications of the genome are generally stable in somatic cells of multicellular organisms. In germ cells and early embryos, however, epigenetic reprogramming occurs on a genome-wide scale, which includes demethylation of DNA and remodeling of histones and their modifications. The mechanisms of genome-wide erasure of DNA methylation, which involve modifications to 5-methylcytosine and DNA repair, are being unraveled. Epigenetic reprogramming has important roles in imprinting, the natural as well as experimental acquisition of totipotency and pluripotency, control of transposons, and epigenetic inheritance across generations. Small RNAs and the inheritance of histone marks may also contribute to epigenetic inheritance and reprogramming. Reprogramming occurs in flowering plants and in mammals, and the similarities and differences illuminate developmental and reproductive strategies. PMID- 21030647 TI - Paramutation's properties and puzzles. AB - Paramutation refers to the process by which homologous DNA sequences communicate in trans to establish meiotically heritable expression states. Although mechanisms are unknown, current data are consistent with the hypothesis that the establishment and heritable transmission of specific chromatin states underlies paramutation. Transcribed, noncoding tandem repeats and proteins implicated in RNA-directed transcriptional silencing in plants and yeast are required for paramutation, yet the specific molecules mediating heritable silencing remain to be determined. PMID- 21030648 TI - Epigenetics in the extreme: prions and the inheritance of environmentally acquired traits. AB - Prions are an unusual form of epigenetics: Their stable inheritance and complex phenotypes come about through protein folding rather than nucleic acid-associated changes. With intimate ties to protein homeostasis and a remarkable sensitivity to stress, prions are a robust mechanism that links environmental extremes with the acquisition and inheritance of new traits. PMID- 21030650 TI - Rate of gas phase association of hydroxyl radical and nitrogen dioxide. AB - The reaction of OH and NO(2) to form gaseous nitric acid (HONO(2)) is among the most influential in atmospheric chemistry. Despite its importance, the rate coefficient remains poorly determined under tropospheric conditions because of difficulties in making laboratory rate measurements in air at 760 torr and uncertainties about a secondary channel producing peroxynitrous acid (HOONO). We combined two sensitive laser spectroscopy techniques to measure the overall rate of both channels and the partitioning between them at 25 degrees C and 760 torr. The result is a significantly more precise value of the rate constant for the HONO(2) formation channel, 9.2 (+/-0.4) * 10(-12) cm(3) molecule(-1) s(-1) (1 SD) at 760 torr of air, which lies toward the lower end of the previously established range. We demonstrate the impact of the revised value on photochemical model predictions of ozone concentrations in the Los Angeles airshed. PMID- 21030651 TI - Direct observation and quantification of CO2 binding within an amine functionalized nanoporous solid. AB - Understanding the molecular details of CO(2)-sorbent interactions is critical for the design of better carbon-capture systems. Here we report crystallographic resolution of CO(2) molecules and their binding domains in a metal-organic framework functionalized with amine groups. Accompanying computational studies that modeled the gas sorption isotherms, high heat of adsorption, and CO(2) lattice positions showed high agreement on all three fronts. The modeling apportioned specific binding interactions for each CO(2) molecule, including substantial cooperative binding effects among the guest molecules. The validation of the capacity of such simulations to accurately model molecular-scale binding bodes well for the theory-aided development of amine-based CO(2) sorbents. The analysis shows that the combination of appropriate pore size, strongly interacting amine functional groups, and the cooperative binding of CO(2) guest molecules is responsible for the low-pressure binding and large uptake of CO(2) in this sorbent material. PMID- 21030652 TI - The occurrence and mass distribution of close-in super-Earths, Neptunes, and Jupiters. AB - The questions of how planets form and how common Earth-like planets are can be addressed by measuring the distribution of exoplanet masses and orbital periods. We report the occurrence rate of close-in planets (with orbital periods less than 50 days), based on precise Doppler measurements of 166 Sun-like stars. We measured increasing planet occurrence with decreasing planet mass (M). Extrapolation of a power-law mass distribution fitted to our measurements, df/dlogM = 0.39 M(-0.48), predicts that 23% of stars harbor a close-in Earth-mass planet (ranging from 0.5 to 2.0 Earth masses). Theoretical models of planet formation predict a deficit of planets in the domain from 5 to 30 Earth masses and with orbital periods less than 50 days. This region of parameter space is in fact well populated, implying that such models need substantial revision. PMID- 21030653 TI - Transferable GaN layers grown on ZnO-coated graphene layers for optoelectronic devices. AB - We fabricated transferable gallium nitride (GaN) thin films and light-emitting diodes (LEDs) using graphene-layered sheets. Heteroepitaxial nitride thin films were grown on graphene layers by using high-density, vertically aligned zinc oxide nanowalls as an intermediate layer. The nitride thin films on graphene layers show excellent optical characteristics at room temperature, such as stimulated emission. As one of the examples for device applications, LEDs that emit strong electroluminescence emission under room illumination were fabricated. Furthermore, the layered structure of a graphene substrate made it possible to easily transfer GaN thin films and GaN-based LEDs onto foreign substrates such as glass, metal, or plastic. PMID- 21030654 TI - Large delta13C gradients in the preindustrial North Atlantic revealed. AB - The carbon isotopic composition ((13)C/(12)C, expressed as delta(13)C) of fossil foraminifera is the primary tracer used to infer changes in past ocean ventilation, and its variations are interpreted by using the modern oceanic delta(13)C distribution as a framework. However, the present ocean delta(13)C distribution is strongly overprinted by isotopically light anthropogenic carbon dioxide. A correction for this oceanic C-13 Suess effect in the North Atlantic (NA) shows that the pristine NA delta(13)C distribution has a richer and more detailed structure that is more clearly related to water mass distributions. Our results revise some fundamental perceptions regarding glacial-interglacial ocean delta(13)C differences and allow paleo-delta(13)C variations to be understood within the context of modern climate variability. PMID- 21030655 TI - Early use of pressure flaking on lithic artifacts at Blombos Cave, South Africa. AB - Pressure flaking has been considered to be an Upper Paleolithic innovation dating to ~20,000 years ago (20 ka). Replication experiments show that pressure flaking best explains the morphology of lithic artifacts recovered from the ~75-ka Middle Stone Age levels at Blombos Cave, South Africa. The technique was used during the final shaping of Still Bay bifacial points made on heat-treated silcrete. Application of this innovative technique allowed for a high degree of control during the detachment of individual flakes, resulting in thinner, narrower, and sharper tips on bifacial points. This technology may have been first invented and used sporadically in Africa before its later widespread adoption. PMID- 21030656 TI - Fitness correlates of heritable variation in antibody responsiveness in a wild mammal. AB - A functional immune system is important for survival in natural environments, where individuals are frequently exposed to parasites. Yet strong immune responses may have fitness costs if they deplete limited energetic resources or cause autoimmune disease. We have found associations between fitness and heritable self-reactive antibody responsiveness in a wild population of Soay sheep. The occurrence of self-reactive antibodies correlated with overall antibody responsiveness and was associated with reduced reproduction in adults of both sexes. However, in females, the presence of self-reactive antibodies was positively associated with adult survival during harsh winters. Our results highlight the complex effects of natural selection on immune responsiveness and suggest that fitness trade-offs may maintain immunoheterogeneity, including genetic variation in autoimmune susceptibility. PMID- 21030657 TI - Filtering of visual information in the tectum by an identified neural circuit. AB - The optic tectum of zebrafish is involved in behavioral responses that require the detection of small objects. The superficial layers of the tectal neuropil receive input from retinal axons, while its deeper layers convey the processed information to premotor areas. Imaging with a genetically encoded calcium indicator revealed that the deep layers, as well as the dendrites of single tectal neurons, are preferentially activated by small visual stimuli. This spatial filtering relies on GABAergic interneurons (using the neurotransmitter gamma-aminobutyric acid) that are located in the superficial input layer and respond only to large visual stimuli. Photo-ablation of these cells with KillerRed, or silencing of their synaptic transmission, eliminates the size tuning of deeper layers and impairs the capture of prey. PMID- 21030658 TI - Visualizing ribosome biogenesis: parallel assembly pathways for the 30S subunit. AB - Ribosomes are self-assembling macromolecular machines that translate DNA into proteins, and an understanding of ribosome biogenesis is central to cellular physiology. Previous studies on the Escherichia coli 30S subunit suggest that ribosome assembly occurs via multiple parallel pathways rather than through a single rate-limiting step, but little mechanistic information is known about this process. Discovery single-particle profiling (DSP), an application of time resolved electron microscopy, was used to obtain more than 1 million snapshots of assembling 30S subunits, identify and visualize the structures of 14 assembly intermediates, and monitor the population flux of these intermediates over time. DSP results were integrated with mass spectrometry data to construct the first ribosome-assembly mechanism that incorporates binding dependencies, rate constants, and structural characterization of populated intermediates. PMID- 21030649 TI - Diversity of human copy number variation and multicopy genes. AB - Copy number variants affect both disease and normal phenotypic variation, but those lying within heavily duplicated, highly identical sequence have been difficult to assay. By analyzing short-read mapping depth for 159 human genomes, we demonstrated accurate estimation of absolute copy number for duplications as small as 1.9 kilobase pairs, ranging from 0 to 48 copies. We identified 4.1 million "singly unique nucleotide" positions informative in distinguishing specific copies and used them to genotype the copy and content of specific paralogs within highly duplicated gene families. These data identify human specific expansions in genes associated with brain development, reveal extensive population genetic diversity, and detect signatures consistent with gene conversion in the human species. Our approach makes ~1000 genes accessible to genetic studies of disease association. PMID- 21030660 TI - Cognitive illusions of authorship reveal hierarchical error detection in skilled typists. AB - The ability to detect errors is an essential component of cognitive control. Studies of error detection in humans typically use simple tasks and propose single-process theories of detection. We examined error detection by skilled typists and found illusions of authorship that provide evidence for two error detection processes. We corrected errors that typists made and inserted errors in correct responses. When asked to report errors, typists took credit for corrected errors and accepted blame for inserted errors, claiming authorship for the appearance of the screen. However, their typing rate showed no evidence of these illusions, slowing down after corrected errors but not after inserted errors. This dissociation suggests two error-detection processes: one sensitive to the appearance of the screen and the other sensitive to keystrokes. PMID- 21030659 TI - A size threshold limits prion transmission and establishes phenotypic diversity. AB - According to the prion hypothesis, atypical phenotypes arise when a prion protein adopts an alternative conformation and persist when that form assembles into self replicating aggregates. Amyloid formation in vitro provides a model for this protein-misfolding pathway, but the mechanism by which this process interacts with the cellular environment to produce transmissible phenotypes is poorly understood. Using the yeast prion Sup35/[PSI(+)], we found that protein conformation determined the size distribution of aggregates through its interactions with a molecular chaperone. Shifts in this range created variations in aggregate abundance among cells because of a size threshold for transmission, and this heterogeneity, along with aggregate growth and fragmentation, induced age-dependent fluctuations in phenotype. Thus, prion conformations may specify phenotypes as population averages in a dynamic system. PMID- 21030661 TI - Associations of the Stair Climb Power Test with muscle strength and functional performance in people with chronic obstructive pulmonary disease: a cross sectional study. AB - BACKGROUND: The Stair Climb Power Test (SCPT) is a functional test associated with leg muscle power in older people. OBJECTIVE: The purposes of this study were to compare the results of the SCPT in people with chronic obstructive pulmonary disease (COPD) and people who were healthy and to explore associations of the SCPT with muscle strength (force-generating capacity) and functional performance. DESIGN: The study was a cross-sectional investigation. METHODS: Twenty-one people with COPD and a predicted mean (SD) percentage of forced expiratory volume in 1 second of 47.2 (12.9) and 21 people who were healthy and matched for age, sex, and body mass were tested with the SCPT. Knee extensor and flexor muscle torque was assessed with an isokinetic dynamometer. Functional performance was assessed with the Timed "Up & Go" Test (TUG) and the Six-Minute Walk Test (6MWT). RESULTS: People with COPD showed lower values on the SCPT (28%) and all torque measures (~ 32%), except for eccentric knee flexor muscle torque. In people with COPD, performance on the TUG and 6MWT was lower by 23% and 28%, respectively. In people with COPD, the SCPT was moderately associated with knee extensor muscle isometric and eccentric torque (r >=.46) and strongly associated (r=.68) with the 6MWT. In people who were healthy, the association of the SCPT with knee extensor muscle torque tended to be stronger (r >=.66); however, no significant relationship between the SCPT and measures of functional performance was found. LIMITATIONS: The observational design of the study and the use of a relatively small convenience sample limit the generalizability of the findings. CONCLUSIONS: The SCPT is a simple and safe test associated with measures of functional performance in people with COPD. People with COPD show deficits on the SCPT. However, the SCPT is only moderately associated with muscle torque and thus cannot be used as a simple surrogate for muscle strength in people with COPD. PMID- 21030662 TI - Construct validity of the assessment of balance in children who are developing typically and in children with hearing impairments. AB - BACKGROUND: Children with hearing impairments have a higher risk for deficits in balance and gross motor skills compared with children who are developing typically. As balance is a fundamental ability for the motor development of children, a valid and reliable assessment to identify weaknesses in balance is crucial. OBJECTIVE: The purpose of this study was to investigate the construct validity of posturography and clinical balance tests in children with hearing impairments and in children who are developing typically. METHODS: The study involved 53 children with typical development and 23 children with hearing impairments who were between 6 and 12 years of age and without neuromotor or orthopedic disorders. All participants completed 3 posturography tests (modified Clinical Test of Sensory Interaction of Balance [mCTSIB], unilateral stance, and tandem stance) and 4 clinical balance tests (one-leg stance with eyes open and with eyes closed, balance beam walking, and one-leg hopping). RESULTS: Three conditions of the mCTSIB, unilateral stance, and 2 clinical balance tests were able to distinguish significantly between the 2 groups. Children with hearing impairments showed more difficulties in balance tasks compared with children who were developing typically when 1 or 2 types of sensory information were eliminated or disturbed. The study showed only low to moderate correlations among the different methods of evaluating balance. CONCLUSIONS: Clinical balance tests and posturography offer different but complementary information. An assessment protocol for balance consisting of posturography and clinical balance tasks is proposed. Static and dynamic balance abilities could not be differentiated and seem not to be a valid dichotomy. PMID- 21030663 TI - The emerging relationship between regenerative medicine and physical therapeutics. AB - Dramatic changes in the health care landscape over the next few decades undoubtedly will affect rehabilitation specialists' practice. In the multidisciplinary field of regenerative medicine, cell, tissue, or organ substitutes are used to enhance the healing potential of the body. Given that the restoration of normal functioning of injured or diseased tissues is expected to be the ultimate goal of these therapies, the future of regenerative medicine is, undeniably, tightly intertwined with that of rehabilitation. Rehabilitation specialists not only must be aware of cutting-edge medical advances as they relate to regenerative medicine but also must work closely with basic scientists to guide the development of clinically relevant protocols. The purposes of this article are to provide a current perspective on biological approaches to the management of musculoskeletal disorders and to highlight the needed integration of physical therapeutics with regenerative medicine. PMID- 21030664 TI - An early circulating factor in severe sepsis modulates apoptosis of monocytes and lymphocytes. AB - We hypothesized that a factor may circulate in serum early during sepsis, modulating apoptosis of monocytes and lymphocytes. Serum was collected from 20 healthy volunteers and from 48 patients with severe sepsis/shock within 12 h from signs of the first failing organ. PBMCs were isolated from 20 healthy volunteers and incubated with collected sera. Apoptosis and expression of CD95 were determined by flow cytometry; experiments were run in the presence of caspase-8 and caspase-9 inhibitors and of CaCl(2). Activity of caspase-3 was determined in cell lysates by a chromogenic kinetic assay. Incubation with serum of patients induced apoptosis of CD4 lymphocytes and inhibited apoptosis of CD14 monocytes. This was attenuated after diluting serum or mixing with healthy serum. Activity of caspase-3 was consistent with these findings. Induced apoptosis of CD4 lymphocytes was greater among nonsurvivors, and it was inhibited in the presence of caspase inhibitors. Inhibitors did not modify the effect of patients' serum on apoptosis of CD14 monocytes. CaCl(2) reversed the inhibitory effect on apoptosis of CD14 moncytes. The above findings support the hypothesis for the existence of an early circulating factor in severe sepsis/shock, modulating apoptosis of CD4 lymphocytes and of CD14 monocytes by interaction with the two apoptotic pathways. PMID- 21030665 TI - Nutritional modulation of training-induced skeletal muscle adaptations. AB - Skeletal muscle displays remarkable plasticity, enabling substantial adaptive modifications in its metabolic potential and functional characteristics in response to external stimuli such as mechanical loading and nutrient availability. Contraction-induced adaptations are determined largely by the mode of exercise and the volume, intensity, and frequency of the training stimulus. However, evidence is accumulating that nutrient availability serves as a potent modulator of many acute responses and chronic adaptations to both endurance and resistance exercise. Changes in macronutrient intake rapidly alter the concentration of blood-borne substrates and hormones, causing marked perturbations in the storage profile of skeletal muscle and other insulin sensitive tissues. In turn, muscle energy status exerts profound effects on resting fuel metabolism and patterns of fuel utilization during exercise as well as acute regulatory processes underlying gene expression and cell signaling. As such, these nutrient-exercise interactions have the potential to activate or inhibit many biochemical pathways with putative roles in training adaptation. This review provides a contemporary perspective of our understanding of the molecular and cellular events that take place in skeletal muscle in response to both endurance and resistance exercise commenced after acute and/or chronic alterations in nutrient availability (carbohydrate, fat, protein, and several antioxidants). Emphasis is on the results of human studies and how nutrient provision (or lack thereof) interacts with specific contractile stimulus to modulate many of the acute responses to exercise, thereby potentially promoting or inhibiting subsequent training adaptation. PMID- 21030667 TI - Intracoronary gastrin 17 increases cardiac perfusion and function through autonomic nervous system, CCK receptors, and nitric oxide in anesthetized pigs. AB - The release of gastrointestinal hormones has been reported to modulate reflex cardiovascular responses caused by gastric distension, although the role played by gastrin 17 is as yet unknown. The present study was therefore planned to determine the primary in vivo effect of gastrin 17 on coronary blood flow and cardiac function and the involvement of autonomic nervous system, CCK1/2 receptors, and nitric oxide (NO). In 40 anesthetized pigs, gastrin 17 was infused into the left anterior descending coronary artery at constant heart rate and arterial blood pressure. In 35 of the 40 pigs, the mechanisms of the observed hemodynamic responses were analyzed by repeating gastrin 17 infusion after autonomic nervous system and NO blockade, and after specific CCK receptors agonists/antagonists administration. Intracoronary gastrin 17 administration caused dose-related increases of both coronary blood flow and cardiac function. The intracoronary co-administration of CCK33/pentagastrin and gastrin 17 potentiated the coronary effects observed when the above agents were given alone (P <0.05). The potentiation of the cardiac response was observed only with the co administration of pentagastrin and gastrin 17 (P <0.05). Moreover, blockade of muscarinic cholinoceptors (intravenous atropine) and of alpha-adrenoceptors (intravenous phentolamine) did not abolish the hemodynamic responses to gastrin 17. The cardiac and vascular effects of the hormone were prevented by blockade of beta-adrenoceptors (intravenous atenolol and butoxamine), CCK1/2 receptors (intracoronary lorglumide and CAM-1028), and NO synthase (intracoronary Nomega nitro-l-arginine methyl ester). In conclusion, gastrin 17 primarily increased coronary blood flow and cardiac function through the involvement of CCK receptors, beta-adrenoceptors, and NO release. PMID- 21030666 TI - Variability in training-induced skeletal muscle adaptation. AB - When human skeletal muscle is exposed to exercise training, the outcomes, in terms of physiological adaptation, are unpredictable. The significance of this fact has long been underappreciated, and only recently has progress been made in identifying some of the molecular bases for the heterogeneous response to exercise training. It is not only of great medical importance that some individuals do not substantially physiologically adapt to exercise training, but the study of the heterogeneity itself provides a powerful opportunity to dissect out the genetic and environmental factors that limit adaptation, directly in humans. In the following review I will discuss new developments linking genetic and transcript abundance variability to an individual's potential to improve their aerobic capacity or endurance performance or induce muscle hypertrophy. I will also comment on the idea that certain gene networks may be associated with muscle "adaptability" regardless the stimulus provided. PMID- 21030668 TI - Initiating inspiration outside the medulla does produce eupneic breathing. PMID- 21030669 TI - Local exposure of the rat cortex to radiofrequency electromagnetic fields increases local cerebral blood flow along with temperature. AB - Few studies have shown that local exposure to radiofrequency electromagnetic fields (RF) induces intensity-dependent physiological changes, especially in the brain. The aim of the present study was to detect reproducible responses to local RF exposure in the parietal cortex of anesthetized rats and to determine their dependence on RF intensity. The target cortex tissue was locally exposed to 2-GHz RF using a figure-eight loop antenna within a range of averaged specific absorption rates (10.5, 40.3, 130, and 263 W/kg averaged over 4.04 mg) in the target area. Local cerebral blood flow (CBF) and temperatures in three regions (target area, rectum, and calf hypodermis) were measured using optical fiber blood flow meters and thermometers during RF exposure. All parameters except for the calf hypodermis temperature increased significantly in exposed animals compared with sham-exposed ones during 18-min exposures. Dependence of parameter values on exposure intensity was analyzed using linear regression models. The elevation of local CBF was correlated with temperature rise in both target and rectum at the end of RF exposure. However, the local CBF elevation seemed to be elevated by the rise in target temperature, but not by that of the rectal temperature, in the early part of RF exposure or at low-intensity RF exposure. These findings suggest that local RF exposure of the rat cortex drives a regulation of CBF accompanied by a local temperature rise, and our findings may be helpful for discussing physiological changes in the local cortex region, which is locally exposed to RF. PMID- 21030670 TI - Mechanisms regulating muscle mass during disuse atrophy and rehabilitation in humans. AB - Muscle mass loss accompanies periods of bedrest and limb immobilization in humans and requires rehabilitation exercise to effectively restore mass and function. Although recent evidence points to an early and transient rise in muscle protein breakdown contributing to this decline in muscle mass, the driving factor seems to be a reduction in muscle protein synthesis, not least in part due to the development of anabolic resistance to amino acid provision. Although the AKT signaling pathway has been identified in small animals as central to the regulation of muscle protein synthesis, several studies in humans have now demonstrated a disassociation between AKT signaling and muscle protein synthesis during feeding, exercise, and immobilization, suggesting that the mechanisms regulating protein synthesis in human skeletal muscle are more complex than initially thought (at least in non-inflammatory states). During rehabilitation, exercise-induced myogenesis may in part be responsible for the recovery of muscle mass. Rapid and sustained exercise-induced suppression of myostatin mRNA expression, that precedes any gain in muscle mass, points to this, along with other myogenic proteins, as being potential regulators of muscle regeneration during exercise rehabilitation in humans. PMID- 21030671 TI - Differential effects of peroxynitrite on contractile protein properties in fast- and slow-twitch skeletal muscle fibers of rat. AB - Oxidative modification of contractile proteins is thought to be a key factor in muscle weakness observed in many pathophysiological conditions. In particular, peroxynitrite (ONOO(-)), a potent short-lived oxidant, is a likely candidate responsible for this contractile dysfunction. In this study ONOO(-) or 3 morpholinosydnonimine (Sin-1, a ONOO(-) donor) was applied to rat skinned muscle fibers to characterize the effects on contractile properties. Both ONOO(-) and Sin-1 exposure markedly reduced maximum force in slow-twitch fibers but had much less effect in fast-twitch fibers. The rate of isometric force development was also reduced without change in the number of active cross bridges. Sin-1 exposure caused a disproportionately large decrease in Ca(2+) sensitivity, evidently due to coproduction of superoxide, as it was prevented by Tempol, a superoxide dismutase mimetic. The decline in maximum force with Sin-1 and ONOO(-) treatments could be partially reversed by DTT, provided it was applied before the fiber was activated. Reversal by DTT indicates that the decrease in maximum force was due at least in part to oxidation of cysteine residues. Ascorbate caused similar reversal, further suggesting that the cysteine residues had undergone S nitrosylation. The reduction in Ca(2+) sensitivity, however, was not reversed by either DTT or ascorbate. Western blot analysis showed cross-linking of myosin heavy chain (MHC) I, appearing as larger protein complexes after ONOO(-) exposure. The findings suggest that ONOO(-) initially decreases maximum force primarily by oxidation of cysteine residues on the myosin heads, and that the accompanying decrease in Ca(2+) sensitivity is likely due to other, less reversible actions of hydroxyl or related radicals. PMID- 21030672 TI - The promoting effect of pentadecapeptide BPC 157 on tendon healing involves tendon outgrowth, cell survival, and cell migration. AB - Pentadecapeptide BPC 157, composed of 15 amino acids, is a partial sequence of body protection compound (BPC) that is discovered in and isolated from human gastric juice. Experimentally it has been demonstrated to accelerate the healing of many different wounds, including transected rat Achilles tendon. This study was designed to investigate the potential mechanism of BPC 157 to enhance healing of injured tendon. The outgrowth of tendon fibroblasts from tendon explants cultured with or without BPC 157 was examined. Results showed that BPC 157 significantly accelerated the outgrowth of tendon explants. Cell proliferation of cultured tendon fibroblasts derived from rat Achilles tendon was not directly affected by BPC 157 as evaluated by MTT assay. However, the survival of BPC 157 treated cells was significantly increased under the H(2)O(2) stress. BPC 157 markedly increased the in vitro migration of tendon fibroblasts in a dose dependent manner as revealed by transwell filter migration assay. BPC 157 also dose dependently accelerated the spreading of tendon fibroblasts on culture dishes. The F-actin formation as detected by FITC-phalloidin staining was induced in BPC 157-treated fibroblasts. The protein expression and activation of FAK and paxillin were determined by Western blot analysis, and the phosphorylation levels of both FAK and paxillin were dose dependently increased by BPC 157 while the total amounts of protein was unaltered. In conclusion, BPC 157 promotes the ex vivo outgrowth of tendon fibroblasts from tendon explants, cell survival under stress, and the in vitro migration of tendon fibroblasts, which is likely mediated by the activation of the FAK-paxillin pathway. PMID- 21030674 TI - High responders to resistance exercise training demonstrate differential regulation of skeletal muscle microRNA expression. AB - MicroRNAs (miRNA), small noncoding RNA molecules, may regulate protein synthesis, while resistance exercise training (RT) is an efficient strategy for stimulating muscle protein synthesis in vivo. However, RT increases muscle mass, with a very wide range of effectiveness in humans. We therefore determined the expression level of 21 abundant miRNAs to determine whether variation in these miRNAs was able to explain the variation in RT-induced gains in muscle mass. Vastus lateralis biopsies were obtained from the top and bottom ~20% of responders from 56 young men who undertook a 5 day/wk RT program for 12 wk. Training-induced muscle mass gain was determined by dual-energy X-ray absorptiometry, and fiber size was evaluated by histochemistry. The expression level of each miRNA was quantified using TaqMan-based quantitative PCR, with the analysis carried out in a blinded manner. Gene ontology and target gene profiling were used to predict the potential biological implications. Of the 21 mature miRNAs examined, 17 were stable during RT in both groups. However, miR-378, miR-29a, miR-26a, and miR-451 were differentially expressed between low and high responders. miR-378, miR-29a, and miR-26a were downregulated in low responders and unchanged in high responders, while miR-451 was upregulated only in low responders. Interestingly, the training-induced change in miR-378 abundance was positively correlated with muscle mass gains in vivo. Gene ontology analysis of the target gene list of miR 378, miR-29a, miR-26a, and miR-451, from the weighted cumulative context ranking methodology, indicated that miRNA changes in the low responders may be compensatory, reflecting a failure to "activate" growth and remodeling genes. We report, for the first time, that RT-induced hypertrophy in human skeletal muscle is associated with selected changes in miRNA abundance. Our analysis indicates that miRNAs may play a role in the phenotypic change and pronounced intergroup variation in the RT response. PMID- 21030673 TI - Regulation of exercise-induced fiber type transformation, mitochondrial biogenesis, and angiogenesis in skeletal muscle. AB - Skeletal muscle exhibits superb plasticity in response to changes in functional demands. Chronic increases of skeletal muscle contractile activity, such as endurance exercise, lead to a variety of physiological and biochemical adaptations in skeletal muscle, including mitochondrial biogenesis, angiogenesis, and fiber type transformation. These adaptive changes are the basis for the improvement of physical performance and other health benefits. This review focuses on recent findings in genetically engineered animal models designed to elucidate the mechanisms and functions of various signal transduction pathways and gene expression programs in exercise-induced skeletal muscle adaptations. PMID- 21030675 TI - Effect of anti-inflammatory medication on the running-induced rise in patella tendon collagen synthesis in humans. AB - NSAIDs are widely used in the treatment of inflammatory diseases as well as of tendon diseases associated with pain in sports and labor. However, the effect of NSAID intake, and thus blockade of PGE(2) production, on the tendon tissue adaptation is unknown. The purpose of the present study was to elucidate the possible effects of NSAID intake on healthy tendon collagen turnover in relation to a strenuous bout of endurance exercise. Fifteen healthy young men were randomly assigned into two experimental groups, with one group receiving indomethacin (oral 2 * 100 mg Confortid daily for 7 days; NSAID; n = 7) and a placebo group (n = 8). Both groups were exposed to a prolonged bout of running (36 km). The collagen synthesis NH2-terminal propeptide of type I (PINP) and PGE2 concentrations were measured before and 72 h following the run in the patella tendon by microdialysis. The peritendinous concentrations of PINP increased significantly in the placebo group as a result of the run, as shown previously. PGE2 levels were significantly decreased 72 h after the run compared with basal levels in the subjects treated with NSAID and unchanged in the placebo group. The NSAID intake abolished the adaptive increase in collagen synthesis in the patella tendon found in the placebo group in response to the prolonged exercise (P < 0.05). The present study demonstrates that intake of NSAID decreased interstitial PGE2 and abolished the exercise-induced adaptive increase in collagen synthesis in human tendons. PMID- 21030676 TI - Muscle activity and time to task failure differ with load compliance and target force for elbow flexor muscles. AB - The primary purpose of this study was to determine the influence of load compliance on time to failure during sustained isometric contractions performed with the elbow flexor muscles at four submaximal target forces. Subjects pulled against a rigid restraint during the force task and maintained a constant elbow angle, while supporting an equivalent inertial load during the position task. Each task was sustained for as long as possible. Twenty-one healthy adults (23 +/ 6 yr; 11 men) participated in the study. The maximal voluntary contraction (MVC) force was similar (P = 0.95) before the subjects performed the force and position tasks at each of the four target forces: 20, 30, 45, and 60% of MVC force. The time to task failure was longer for the force tasks (576 +/- 80 and 325 +/- 70 s) than for the position tasks (299 +/- 77 and 168 +/- 35 s) at target forces of 20 and 30% (P < 0.001), but was similar for the force tasks (178 +/- 35 and 86 +/- 14 s) and the position tasks (132 +/- 29 and 87 +/- 14 s) at target forces of 45 and 60% (P > 0.19). The briefer times to failure for the position task at the lower forces were accompanied by greater rates of increase in elbow flexor muscle activity, mean arterial pressure, heart rate, and rating of perceived exertion. There was no difference in the estimates of external mechanical work at any target force. The dominant mechanisms limiting time to failure of sustained isometric contractions with the elbow flexor muscles appear to change at target forces between 30 and 45% MVC, with load compliance being a significant factor at lower forces only. PMID- 21030677 TI - Histone modifications and exercise adaptations. AB - The spatial association between genomic DNA and histone proteins within chromatin plays a key role in the regulation of gene expression and is largely governed by post-translational modifications to histone proteins, particularly H3 and H4. These modifications include phosphorylation, acetylation, and mono-, di-, and tri methylation, and while some are associated with transcriptional repression, acetylation of lysine residues within H3 generally correlates with transcriptional activation. Histone acetylation is regulated by the balance between the activities of histone acetyl transferase (HAT) and histone deacetylase (HDAC). In skeletal muscle, the class II HDACs 4, 5, 7, and 9 play a key role in muscle development and adaptation and have been implicated in exercise adaptations. As just one example, exercise results in the nuclear export of HDACs 4 and 5, secondary to their phosphorylation by CaMKII and AMPK, two kinases that are activated during exercise in response to changes in sarcoplasmic Ca(2+) levels and energy status, in association with increased GLUT4 expression in human skeletal muscle. Unraveling the complexities of the so-called "histone code" before and after exercise is likely to lead to a greater understanding of the regulation of exercise/activity-induced alterations in skeletal muscle gene expression and reinforce the importance of skeletal muscle plasticity in health and disease. PMID- 21030678 TI - Gene therapy-mediated delivery of targeted cytotoxins for glioma therapeutics. AB - Restricting the cytotoxicity of anticancer agents by targeting receptors exclusively expressed on tumor cells is critical when treating infiltrative brain tumors such as glioblastoma multiforme (GBM). GBMs express an IL-13 receptor (IL13Ralpha2) that differs from the physiological IL4R/IL13R receptor. We developed a regulatable adenoviral vector (Ad.mhIL-4.TRE.mhIL-13-PE) encoding a mutated human IL-13 fused to Pseudomonas exotoxin (mhIL-13-PE) that specifically binds to IL13Ralpha2 to provide sustained expression, effective anti-GBM cytotoxicity, and minimal neurotoxicity. The therapeutic Ad also encodes mutated human IL-4 that binds to the physiological IL4R/IL13R without interacting with IL13Ralpha2, thus inhibiting potential binding of mhIL-13-PE to normal brain cells. Using intracranial GBM xenografts and syngeneic mouse models, we tested the Ad.mhIL-4.TRE.mhIL-13-PE and two protein formulations, hIL-13-PE used in clinical trials (Cintredekin Besudotox) and a second-generation mhIL-13-PE. Cintredekin Besudotox doubled median survival without eliciting long-term survival and caused severe neurotoxicity; mhIL-13-PE led to ~40% long-term survival, eliciting severe neurological toxicity at the high dose tested. In contrast, Ad-mediated delivery of mhIL-13-PE led to tumor regression and long term survival in over 70% of the animals, without causing apparent neurotoxicity. Although Cintredekin Besudotox was originally developed to target GBM, when tested in a phase III trial it failed to achieve clinical endpoints and revealed neurotoxicity. Limitations of Cintredekin Besudotox include its short half-life, which demanded frequent or continued administration, and binding to IL4R/IL13R, present in normal brain cells. These shortcomings were overcome by our therapeutic Ad, thus representing a significant advance in the development of targeted therapeutics for GBM. PMID- 21030680 TI - A biochemical mechanism for the oncogenic potential of the p110beta catalytic subunit of phosphoinositide 3-kinase. AB - Class I PI3-kinases signal downstream of receptor tyrosine kinases and G protein coupled receptors and have been implicated in tumorigenesis. Although the oncogenic potential of the PI3-kinase subunit p110alpha requires its mutational activation, other p110 isoforms can induce transformation when overexpressed in the wild-type state. In wild-type p110alpha, N345 in the C2 domain forms hydrogen bonds with D560 and N564 in the inter-SH2 (iSH2) domain of p85, and mutations of p110alpha or p85 that disrupt this interface lead to increased basal activity and transformation. Sequence analysis reveals that N345 in p110alpha aligns with K342 in p110beta. This difference makes wild-type p110beta analogous to a previously described oncogenic mutant, p110alpha-N345K. We now show that p110beta is inhibited by p85 to a lesser extent than p110alpha and is not differentially inhibited by wild-type p85 versus p85 mutants that disrupt the C2-iSH2 domain interface. Similar results were seen in soft agar and focus-formation assays, where p110beta was similar to p110alpha-N345K in transforming potential. Inhibition of p110beta by p85 was enhanced by a K342N mutation in p110beta, which led to decreased activity in vitro, decreased basal Akt and ribosomal protein S6 kinase (S6K1) activation, and decreased transformation in NIH 3T3 cells. Moreover, unlike wild-type p110beta, p110beta-K342N was differentially regulated by wild-type and mutant p85, suggesting that the inhibitory C2-iSH2 interface is functional in this mutant. This study shows that the enhanced transforming potential of p110beta is the result of its decreased inhibition by p85, due to the disruption of an inhibitory C2-iSH2 domain interface. PMID- 21030679 TI - Molecular mechanisms of retroviral integrase inhibition and the evolution of viral resistance. AB - The development of HIV integrase (IN) strand transfer inhibitors (INSTIs) and our understanding of viral resistance to these molecules have been hampered by a paucity of available structural data. We recently reported cocrystal structures of the prototype foamy virus (PFV) intasome with raltegravir and elvitegravir, establishing the general INSTI binding mode. We now present an expanded set of cocrystal structures containing PFV intasomes complexed with first- and second generation INSTIs at resolutions of up to 2.5 A. Importantly, the improved resolution allowed us to refine the complete coordination spheres of the catalytic metal cations within the INSTI-bound intasome active site. We show that like the Q148H/G140S and N155H HIV-1 IN variants, the analogous S217H and N224H PFV INs display reduced sensitivity to raltegravir in vitro. Crystal structures of the mutant PFV intasomes in INSTI-free and -bound forms revealed that the amino acid substitutions necessitate considerable conformational rearrangements within the IN active site to accommodate an INSTI, thus explaining their adverse effects on raltegravir antiviral activity. Furthermore, our structures predict physical proximity and an interaction between HIV-1 IN mutant residues His148 and Ser/Ala140, rationalizing the coevolution of Q148H and G140S/A mutations in drug resistant viral strains. PMID- 21030681 TI - Germ-line elimination of electric charge on pre-T-cell receptor (TCR) impairs autonomous signaling for beta-selection and TCR repertoire formation. AB - The pre-T-cell receptor (TCR) is crucial for the early T-cell development, but the ligand for pre-TCR remains unidentified. We recently proposed a model that pre-TCR complexes oligomerize spontaneously through interactions of the pre TCRalpha chain. To investigate the mechanism underlying this ligand-independent signaling in vivo, we established knock-in mice that express a pre-TCRalpha mutant lacking charged amino acids (D(22)R(24)R(102)R(117) to A(22)A(24)A(102)A(117); 4A). CD4(+)CD8(+) thymocyte number was significantly reduced in invariant pre-TCRalpha (pTalpha(4A/4A)) mice, whereas CD4(-)CD8(-) thymocytes were unaffected. The percentages of double-negative 3 (DN3) cells and gammadelta T cells were increased in the pTalpha(4A/4A) thymus, indicating that beta-selection is impaired in pTalpha(4A/4A) mice. Pre-TCR-mediated tyrosine phosphorylation and clonal expansion into double-positive thymocytes were also defective in the knock-in mice. Pre-TCR was expressed at higher levels on pTalpha(4A/4A) cell surfaces than on those of the wild type, suggesting that the charged residues in pTalpha are critical for autonomous engagement and subsequent internalization of pre-TCR. Pre-TCR-mediated allelic exclusion of the TCRbeta gene was also inhibited in pTalpha(4A/4A) mice, and thereby, dual TCRbetas were expressed on pTalpha(4A/4A) T cells. Furthermore, the TCRbeta chain variable region (Vbeta) repertoire of mature T cells was significantly altered in pTalpha(4A/4A) mice. These results suggest that charged residues of pTalpha are critical for beta-selection, allelic exclusion, and TCRbeta repertoire formation. PMID- 21030682 TI - Letters in words are read simultaneously, not in left-to-right sequence. PMID- 21030683 TI - Design-based stereology: introduction to basic concepts and practical approaches for estimation of cell number. AB - In regulatory toxicology studies, qualitative histopathological evaluation is the reference standard for assessment of test article-related morphological changes. In certain cases, quantitative analysis may be required to detect more subtle morphological changes, such as small changes in cell number. When the detection of subtle test article-related morphological changes is critical to the decision making process, sensitive quantitative methods are needed. Design-based stereology provides the tools for obtaining accurate, precise quantitative structural data from tissue sections. These tools have the sensitivity necessary to detect small changes by combining statistical sampling principles with geometric analysis of the tissue microstructure. It differs from other morphometric methods based on tissue section analysis by providing estimates that are statistically valid, truly three-dimensional, and referent to the entire organ. Further, because the precision of the stereological analysis procedure can be predicted, studies can be designed and powered to detect subtle, potentially toxicologically significant changes. Although stereological methods have not been widely applied in toxicologic pathology, recent advances have made it feasible to implement these methods in a regulatory toxicology setting, particularly methods for estimation of total cell number. PMID- 21030684 TI - Determining stability of stored samples retrospectively: the validation of glycated albumin. AB - BACKGROUND: Determining the stability of stored samples for assays that were not available at the time of original collection is problematic. To assess sample stability for a relatively new assay of glycated albumin (GA), we first measured GA in fresh samples and in samples stored for 19-23 years. We then compared the regression of the contemporaneous glycohemoglobin (Hb A(1c)) values against the GA results from fresh vs stored samples, reasoning that similar slopes and intercepts would provide strong, albeit indirect, support for the stability of the stored samples for GA measurements. METHODS: We assayed 90 samples frozen for 19-23 years and 90 fresh samples from participants in the Diabetes Control and Complications trial cohort for GA. Hb A(1c) was measured contemporaneously in fresh samples at each time period. A single normal-errors linear model regressed the Hb A(1c) values on the GA, with an additional effect for collection period (fresh vs stored for GA) and the interaction of period and GA. RESULTS: Analysis of the regressions lines between GA and Hb A(1c) revealed intercepts (3.69 and 2.97 for the fresh and stored samples, respectively) and slopes (0.198 vs 0.187) that were not significantly different (P = 0.182 and P = 0.639, respectively). CONCLUSIONS: This simple approach can be used to assess the stability of stored samples in new assays. Samples stored for as long as 23 years are suitable for the GA assay. PMID- 21030685 TI - Tandem mass spectrometry for the direct assay of lysosomal enzymes in dried blood spots: application to screening newborns for mucopolysaccharidosis IVA. AB - BACKGROUND: Treatments are being developed for an increasing number of mucopolysaccharidoses, and early diagnosis is expected to be necessary to maximize the benefits of therapy. Therefore, we developed an assay for N acetylgalactosamine-6-sulfate sulfatase (GALNS), the enzyme deficient in mucopolysaccharidosis IVA (Morquio A syndrome), that is applicable for clinical diagnosis. METHODS: A novel substrate for GALNS was synthesized for a new enzyme activity assay that is based on tandem mass spectrometry and uses dried blood spots (DBSs) as the enzyme source. We optimized the assay conditions, including the substrate concentration, reaction pH, lead formate concentration, incubation time, punch size of the DBS, and mass spectrometer conditions. We also assessed inter- and intraassay variation. RESULTS: The assay uses either solid-phase or liquid-phase extraction before analysis by mass spectrometry. An evaluation of blood spots from 90 randomly chosen healthy newborns and 9 patients with Morquio A syndrome showed a well-defined interval between their respective enzyme activities. Inter- and intraassay imprecision was <10%. CONCLUSIONS: This tandem mass spectrometry assay requires a minimal number of sample-preparation steps, thus making it easy to implement. The assay has the potential to be adopted for early diagnosis of Morquio A syndrome. We believe this assay could be performed in a multiplex fashion with assays for other lysosomal enzymes. PMID- 21030686 TI - Increased homocysteine in a patient diagnosed with Marfan syndrome. PMID- 21030687 TI - Commentary. PMID- 21030688 TI - Commentary. PMID- 21030689 TI - Conflicting calcium concentrations in the presence of low albumin after bone marrow transplantation. PMID- 21030692 TI - JNK regulates binding of alpha-catenin to adherens junctions and cell-cell adhesion. AB - We recently reported that c-Jun N-terminal kinase (JNK) is associated with adherens junctions and phosphorylates beta-catenin at serine 33/37 and threonine 41. Here, we report that inhibition of JNK led to formation of adherens junctions, which was accompanied by dissociation of alpha-catenin from the beta catenin/E-cadherin complex and increased association of alpha-catenin with the cytoskeleton. Conversely, activation of JNK increased binding of alpha-catenin to beta-catenin, which was blocked by the JNK inhibitor SP600125 or JNK siRNA. In addition, inhibition of JNK failed to lead to adherens junction formation in cells where alpha-catenin was absent or knocked down. Conversely, introduction of alpha-catenin restored the responsiveness of cells to JNK inhibition and led to cell-cell adhesion. Experiments with domain deletion mutants showed that binding of alpha-catenin to beta-catenin was required for transport of adherens junction complexes to the cell surface, while binding to actin was required for translocation to the cell-cell contact sites. Collectively, our results suggest that JNK affects the association of alpha-catenin with the adherens junction complex and regulates adherens junctions. PMID- 21030693 TI - GPCR structure and activation: an essential role for the first extracellular loop in activating the adenosine A2B receptor. AB - The highly variable extracellular loops in G protein-coupled receptors (GPCRs) have been implicated in receptor activation, the mechanism of which is poorly understood. In a random mutagenesis screen on the human adenosine A(2B) receptor (A(2B)R) using the MMY24 Saccharomyces cerevisiae strain as a read-out system, we found that two residues in the first extracellular loop, a phenylalanine and an aspartic acid at positions 71 and 74, respectively, are involved in receptor activation. We subsequently performed further site-directed and site-saturation mutagenesis. These experiments revealed that the introduction of mutations at either of the identified positions results in a wide variety of receptor activation profiles, with changes in agonist potency, constitutive activity, and intrinsic activity. Radioligand binding studies showed that the changes in activation were not due to changes in receptor expression. We interpret these data in the light of the recently revealed structure of the adenosine A(2A)R, the closest homologue of the A(2B)R. The two residues are suggested to be vital in maintaining the tertiary structure of a beta sheet in the extracellular domain of the A(2B)R. We hypothesize that deterioration of structure in the extracellular domains of GPCRs compromises overall receptor structure with profound consequences for receptor activation and constitutive activity. PMID- 21030694 TI - Retinal vascular calibers and the risk of intracerebral hemorrhage and cerebral infarction: the Rotterdam Study. AB - BACKGROUND AND PURPOSE: Narrower retinal arteriolar calibers and wider venular calibers are associated with cardiovascular disease, including cerebral infarction. We investigated the association between retinal vascular calibers and the long-term risk for stroke and its subtypes with particular focus on intracerebral hemorrhage. METHODS: We included 5518 participants (aged >= 55 years) from the prospective population-based Rotterdam Study who were stroke-free at baseline (1990-1993) and of whom digital retinal images were available. Follow up for incident stroke was complete up to January 1, 2007. Data were analyzed with Cox proportional hazards models adjusted for age and sex and additionally for potential confounders. Arteriolar and venular calibers were entered both separately and simultaneously in the models. RESULTS: During an average follow-up of 11.5 years, 623 participants developed a first-ever stroke (50 hemorrhagic, 361 ischemic, 212 unspecified). Larger venular caliber was independently associated with an increased risk for stroke (hazard ratio [HR] per SD increase: 1.20; 95% confidence interval [CI]: 1.09 to 1.33), cerebral infarction (HR: 1.28; 95% CI: 1.13 to 1.46), and intracerebral hemorrhage (HR: 1.53; 95% CI: 1.09 to 2.15). Much weaker, only borderline significant associations were found between arteriolar caliber and risk for stroke (HR per SD decrease: 1.12; 95% CI: 0.99 to 1.23), cerebral infarction (HR: 1.12; 95% CI, 0.98 to 1.27), and intracerebral hemorrhage (HR: 1.25; 95% CI: 0.87 to 1.79). Retinal vascular calibers were strongly associated with lobar hemorrhages and oral anticoagulant-related hemorrhages. CONCLUSIONS: Larger retinal venular caliber is associated with an increased risk for stroke in the general population and, in particular, with an increased risk for intracerebral hemorrhage. PMID- 21030695 TI - Management of acute stroke patients with rapidly resolving deficits and persistent vascular occlusion: a real clinical equipoise. PMID- 21030696 TI - Hypertension and cerebral diffusion tensor imaging in small vessel disease. AB - BACKGROUND AND PURPOSE: Hypertension is a risk factor for cerebral small vessel disease, which includes white matter lesions (WML) and lacunar infarcts. These lesions are frequently observed on MRI scans of elderly people and play a role in cognitive decline. Preferably, one would like to evaluate the effect of hypertension before fluid-attenuated inversion recovery visible macrostructural lesions occur, possibly by investigating its effect on the microstructural integrity of the white matter. Diffusion tensor imaging provides measures of structural integrity. METHODS: In 503 patients with small vessel disease, aged between 50 and 85 years, we cross-sectionally studied the relation between blood pressure, hypertension, and hypertension treatment status and diffusion tensor imaging parameters in both normal-appearing white matter (NAWM) and WMLs. All of the subjects underwent 1.5-T MRI and diffusion tensor imaging scanning. Fractional anisotropy and mean diffusivity were calculated in both NAWM and WMLs. RESULTS: Increased blood pressure and hypertension were significantly related to lower fractional anisotropy in both NAWM and WMLs and to higher mean diffusivity in WMLs. For hypertensives, odds ratios for the risk of impaired microstructural integrity (fractional anisotropy) were 3.1 (95% CI: 1.8 to 5.7) and 2.1 (95% CI: 1.2 to 3.5) in NAWM and WMLs, respectively, compared with normotensives. Fractional anisotropy odds ratios for treated uncontrolled subjects were 6.5 (95% CI: 3.3 to 12.7) and 2.7 (95% CI: 1.5 to 5.1) in NAWM and WMLs, respectively, compared with normotensives. CONCLUSIONS: Our data show that diffusion tensor imaging may be an appropriate tool to monitor the effect of blood pressure and the response to treatment on white matter integrity, probably even before the development of WMLs on fluid-attenuated inversion recovery. PMID- 21030697 TI - No-go to tissue plasminogen activator for transient ischemic attack. PMID- 21030698 TI - Pro: intravenous tissue plasminogen activator in stroke patients with rapid, complete recovery during evaluation (transient ischemic attack) and evidence of middle cerebral artery occlusion. PMID- 21030699 TI - Maps of time to maximum and time to peak for mismatch definition in clinical stroke studies validated with positron emission tomography. AB - BACKGROUND AND PURPOSE: Perfusion-weighted imaging-derived maps of time-to maximum (Tmax) are increasingly used to identify the tissue at risk in clinical stroke studies (eg, DEFUSE and EPITHET). Using quantitative positron emission tomography (PET), we evaluated Tmax to define the penumbral flow threshold in stroke patients and compared its performance to nondeconvolved time-to-peak (TTP) maps. METHODS: Comparative perfusion-weighted imaging and quantitative 15O-water PET images of acute stroke patients were analyzed using cortical regions of interest. A receiver-operating characteristic curve analysis described the threshold independent performance of Tmax (area under the curve) and identified the best threshold (equal sensitivity and specificity threshold) to identify penumbral flow (< 20 mL/100 g/min on PET cerebral blood flow). The results were compared with nondeconvolved TTP and other current perfusion-weighted imaging maps using the Mann-Whitney rank-sum test. RESULTS: In 26 patients (time delay between MRI and PET, 65 minutes), the best threshold for penumbral flow was 5.5 seconds for Tmax (median; interquartile range, 3.9-6.6; sensitivity/specificity, 88%/89%). The area under the curve value was 0.95 (median; interquartile range, 0.93-0.97). Deconvolved Tmax did not perform significantly better than TTP (P = 0.34). CONCLUSIONS: Maps of Tmax detected penumbral flow but did not perform better than the easy-to-obtain maps of nondeconvolved TTP. Thus, "simple" TTP maps still remain suitable for clinical stroke studies if detailed postprocessing is not feasible. PMID- 21030700 TI - Residual vessel length on magnetic resonance angiography identifies poor responders to alteplase in acute middle cerebral artery occlusion patients: exploratory analysis of the Japan Alteplase Clinical Trial II. AB - BACKGROUND AND PURPOSE: It remains unknown whether the effects of 0.6 mg/kg alteplase differ with occlusion site of the middle cerebral artery (MCA). We therefore evaluated the effects of 0.6 mg/kg intravenous alteplase in patients with different sites of MCA occlusion. METHODS: An exploratory analysis was made of 57 patients enrolled in the Japan Alteplase Clinical Trial II (J-ACT II), originally designed to evaluate 0.6 mg/kg alteplase in Japanese patients with unilateral occlusion of the MCA (M1 or M2 portion). The residual vessel length (in mm), determined by pretreatment magnetic resonance angiography, was used to reflect the occluded site. The proportions of patients with valid recanalization (modified Mori grade 2 to 3) at 6 and 24 hours and a modified Rankin Scale (mRS) score of 0 to 1 and of 0 to 2 at 3 months were compared between the groups dichotomized according to length of the residual vessel. Multiple logistic regression models were generated to elucidate the predictors of valid recanalization, mRS 0 to 1, and mRS 0 to 2. RESULTS: Receiver operating characteristics analysis revealed that 5 mm was the practical cutoff length for dichotomization. In patients with an M1 length < 5 mm (n = 12), the frequencies of valid recanalization at 6 and 24 hours (16.7% and 25.0%) were significantly lower compared with those (62.1% and 82.8%, respectively) of the 45 patients with a residual M1 length >= 5 mm and an M2 occlusion (P = 0.008 for 6 hours, P < 0.001 for 24 hours). The proportions of patients who achieved an mRS of 0 to 1 and an mRS of 0 to 2 were also lower for those with an M1 length < 5 mm (8.3% and 16.7%, respectively) compared with the other group (57.8% and 68.9%, respectively; P = 0.003 for mRS 0 to 1, P = 0.002 for mRS 0 to 2). In logistic regression models, the site of MCA occlusion (< 5 mm) was a significant predictor of valid recanalization at 6 and 24 hours and of an mRS of 0 to 1 and of mRS of 0 to 2. CONCLUSIONS: In patients with acute MCA occlusion, a residual vessel length < 5 mm on magnetic resonance angiography can identify poor responders to 0.6 mg/kg alteplase. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00412867. PMID- 21030701 TI - Personalized approaches to clopidogrel therapy: are we there yet? AB - Clopidogrel is one of the most commonly prescribed medications worldwide. Recent advisories from the US Food and Drug Administration have drawn attention to the possibility of personalized decision-making for people who are candidates for clopidogrel. As is the case with antihypertensives, statins, and warfarin, common genetic sequence variants can influence clopidogrel metabolism and its effect on platelet activity. These genetic variants have, in multiple studies, been associated with adverse clinical outcomes. Concurrent medication use also influences how the body handles clopidogrel. Proton pump inhibitors, widely prescribed in conjunction with clopidogrel, may blunt its effectiveness. We address implications for bedside decision-making in light of accumulated data and current Food and Drug Administration advisories and conclude that genetic testing for CYP2C19 genotype and limitation of proton pump inhibitor interactions do not yet appear to offer an opportunity to optimize treatment given the current state of knowledge. PMID- 21030702 TI - Cerebral microbleeds in the elderly: a pathological analysis. AB - BACKGROUND AND PURPOSE: Cerebral microbleeds in the elderly are routinely identified by brain MRI. The purpose of this study was to better characterize the pathological basis of microbleeds. METHODS: We studied postmortem brain specimens of 33 individuals with no clinical history of stroke and with an age range of 71 to 105 years. Cerebral microbleeds were identified by presence of hemosiderin (iron), identified by routine histochemistry and Prussian blue stain. Cellular localization of iron (in macrophages and pericytes) was studied by immunohistochemistry for smooth muscle actin, CD68, and, in selected cases, electron microscopy. Presence of beta-amyloid was analyzed using immunohistochemistry for epitope 6E10. RESULTS: Cerebral microbleeds were present in 22 cases and occurred at capillary, small artery, and arteriolar levels. Presence of microbleeds occurred independent of amyloid deposition at site of microbleeds. Although most subjects had hypertension, microbleeds were present with and without hypertension. Putamen was the site of microbleeds in all but 1 case; 1 microbleed was in subcortical white matter of occipital lobe. Most capillary microbleeds involved macrophages, but the 2 microbleeds studied by electron microscopy demonstrated pericyte involvement. CONCLUSIONS: These findings indicate that cerebral microbleeds are common in elderly brain and can occur at the capillary level. PMID- 21030703 TI - Optimal timing of resumption of warfarin after intracranial hemorrhage. AB - BACKGROUND AND PURPOSE: The optimum timing of resumption of anticoagulation after warfarin-related intracranial hemorrhage in patients with indication for continued anticoagulation is uncertain. We performed a large retrospective cohort study to obtain more precise risk estimates. METHODS: We reviewed charts of 2869 consecutive patients with objectively verified intracranial hemorrhage over 6 years at 3 tertiary centers. We calculated the daily risk of intracranial hemorrhage or ischemic stroke with and without resumption of warfarin; we focused on patients who survived the first week and had cardiac indication for anticoagulation or previous stroke. Using a Cox model, we estimated rates for these 2 adverse events in relation to different time points of resumed anticoagulation. The combined risk of either a new intracranial hemorrhage or an ischemic stroke was calculated for a range of warfarin resumption times. RESULTS: We identified warfarin-associated intracranial hemorrhage in 234 patients (8.2%), of whom 177 patients (76%) survived the first week and had follow-up information available; the median follow-up time was 69 weeks (interquartile range [IQR] 19 144). Fifty-nine patients resumed warfarin after a median of 5.6 weeks (IQR 2.6 17). The hazard ratio for recurrent intracranial hemorrhage with resumption of warfarin was 5.6 (95% CI, 1.8-17.2), and for ischemic stroke it was 0.11 (95% CI, 0.014-0.89). The combined risk of recurrent intracranial hemorrhage or ischemic stroke reached a nadir if warfarin was resumed after approximately 10 to 30 weeks. CONCLUSIONS: The optimal timing for resumption of warfarin therapy appears to be between 10 and 30 weeks after warfarin-related intracranial hemorrhage. PMID- 21030704 TI - Influence of prophylactic, endovascularly based normothermia on inflammation in patients with severe cerebrovascular disease: a prospective, randomized trial. AB - BACKGROUND AND PURPOSE: We analyzed the impact of long-term endovascularly based prophylactic normothermia versus conventional temperature management on inflammatory parameters in patients with severe cerebrovascular disease. METHODS: This was a prospective, randomized, controlled trial comparing the course of inflammatory parameters between the 2 treatment arms: (1) prophylactically endovascular long-term normothermia; and (2) conventional, stepwise fever management with antiinflammatory drugs and surface cooling. Inclusion criteria were (1) spontaneous subarachnoid hemorrhage with Hunt-Hess grade between 3 and 5; (2) spontaneous intracerebral hemorrhage with a Glasgow Coma Scale score of <= 10; or (3) complicated cerebral infarction requiring intensive care unit treatment with a NIH Stroke Scale score of >= 15. Treatment period was 336 hours in subarachnoid hemorrhage patients and 168 hours in patients with complicated stroke or intracerebral hemorrhage patients. RESULTS: A total of 102 patients (56 female) were enrolled during a 3.5-year period. Overall median total fever burden during the course of treatment was 0.0 degrees C hour and 4.3 degrees C hours in the catheter and conventional group, respectively (P < 0.0001). C-reactive protein and interleukin-6 were significantly elevated in the endovascular group (P < 0.05). Nonsteroidal antiinflammatory drugs, used as additional treatment of fever, significantly reduced mean C-reactive protein in endovascular treated patients (P < 0.01). CONCLUSIONS: The proinflammatory cytokines C-reactive protein and interleukin-6 were significantly elevated in patients receiving prophylactic endovascularly based long-term normothermia. Nonsteroidal antiinflammatory drugs significantly affected the course of proinflammatory parameters; thus, future trials should investigate the role of nonsteroidal antiinflammatory drugs in severe cerebrovascular disease patients and their interaction with temperature management. Clinical Trial Registration-Trial not registered; enrollment began before July 2005. PMID- 21030705 TI - Surgical or medical management for asymptomatic carotid stenosis. PMID- 21030706 TI - Reliability of structured modified rankin scale assessment. PMID- 21030707 TI - Endovascular treatment of very small unruptured aneurysms: rate of procedural complications, clinical outcome, and anatomical results. AB - BACKGROUND AND PURPOSE: The strategy of treatment of small unruptured intracranial aneurysms is complex because of their presumably low risk of rupture. A precise knowledge of the perioperative complications in this specific subgroup is mandatory. The purpose of this study was to compare the results of the endovascular treatment of aneurysms <= 3 mm and aneurysms > 3 mm included in the Analysis of Treatment by Endovascular Approach of Nonruptured Aneurysms study. METHODS: The study included 626 patients harboring 682 unruptured aneurysms. Perioperative adverse events and clinical outcome were analyzed in patients treated for aneurysms <= 3 mm (51 patients, 51 aneurysms) and in patients treated for aneurysms > 3 mm (575 patients, 631 aneurysms). RESULTS: Endovascular treatment failed more often in aneurysms <= 3 mm (13.7%) compared to aneurysms > 3 mm (3.3%; P = 0.003). The rate of intraoperative rupture for aneurysms <= 3 mm (3.9%; 95% CI, 0.5-13.5) did not significantly differ compared to aneurysms > 3 mm (2.4%; 95% CI, 1.2-3.6; P = 0.37). Thromboembolic events were not significantly different in both groups (3.9%; 95% CI, 0.5-13.5 in very small aneurysms and 7.1%; 95% CI, 5.1-9.1 in larger aneurysms; P = 0.57). One month morbidity/mortality was not significantly different for patients with very small aneurysms (2.0%; 95% CI, 0.05-10.45) and for patients with larger aneurysms (3.3%; 95% CI, 1.8-4.8; P = 0.60). CONCLUSIONS: The risks of endovascular treatment are similar in patients with very small or with larger aneurysms. Because the risk of spontaneous rupture is lower in very small aneurysms, their management will include follow-up MRI and active treatment in case of morphological modification. PMID- 21030708 TI - Ongoing randomized controlled trials comparing interventional methods and optimal medical treatment in the treatment of asymptomatic carotid stenosis. PMID- 21030709 TI - The safety of driving a commercial motor vehicle after a stroke. AB - BACKGROUND AND PURPOSE: Current guidelines for commercial motor vehicle (CMV) drivers to return to driving after a TIA or stroke was last reviewed in 1988. Updated recommendations are presented based on recent evidence. METHODS: A 3 member medical expert panel chosen by the U.S. Department of Transportation's Federal Motor Carrier Safety Administration used findings of systematic literature review up to January 2008 to provide updated recommendations for return to driving for CMV drivers after TIA or stroke. RESULTS: Evidence from the systematic review showed that TIA patients are at increased risk for stroke, and stroke patients are at increased risk for motor vehicle crash. Although no studies provide direct evidence of predictability of crash risk of CMV drivers using outcomes of neuropsychological assessments, there is evidence that certain neuropsychological tests can identify on-road driving performance after stroke. CONCLUSIONS: The medical expert panel recommended driving cessation for 1 year after a TIA or stroke, and return to driving a CMV should be allowed only after successful completion of a comprehensive neurological evaluation, neuropsychological assessments, and on-road testing. PMID- 21030710 TI - Influence of age on outcome from thrombolysis in acute stroke: a controlled comparison in patients from the Virtual International Stroke Trials Archive (VISTA). AB - BACKGROUND AND PURPOSE: Thrombolysis for acute ischemic stroke in patients aged > 80 years is not approved in some countries due to limited trial data in the very elderly. We compared outcomes between thrombolysed and nonthrombolysed (control) patients from neuroprotection trials to assess any influence of age on response. Method-Among patients with ischemic stroke of known age, pretreatment severity (baseline National Institutes of Health Scale Score), and 90-day outcome (modified Rankin Scale score; National Institutes of Health Scale score), we compared the distribution of modified Rankin score in thrombolysed patients with control subjects by Cochran-Mantel-Haenszel test and then logistic regression after adjustment for age and baseline National Institutes of Health Scale score. We examined patients <= 80 and >= 81 years separately and then each age decile. RESULTS: Rankin data were available for 5817 patients, 1585 thrombolysed and 4232 control subjects; 20.5% were aged > 80 years (mean +/- SD, 85.1 +/- 3.4 years). Baseline severity was higher among thrombolysed than control subjects (median National Institutes of Health Scale score 14 versus 13, P < 0.05). The distribution of modified Rankin Scale scores was better among thrombolysed patients (P < 0.0001; OR, 1.39; 95% CI, 1.26 to 1.54). The association occurred independently with similar magnitude among young (P < 0.0001; OR, 1.42; 95% CI, 1.26 to 1.59) and elderly (P = 0.002; OR, 1.34; 95% CI, 1.05 to 1.70) patients. ORs were consistent across all age deciles > 30 years; outcomes assessed by National Institutes of Health Scale score gave supporting significant findings, and dichotomized modified Rankin Scale score outcomes were also consistent. CONCLUSIONS: Outcome after thrombolysis for acute ischemic stroke was significantly better than in control subjects. Despite the expected poorer outcomes among elderly compared with young patients that is independent of any treatment effect, the association between thrombolysis treatment and improved outcome is maintained in the very elderly. Age alone should not be a barrier to treatment. PMID- 21030711 TI - Asymptomatic hemorrhagic transformation of infarction and its relationship with functional outcome and stroke subtype: assessment from the Tinzaparin in Acute Ischaemic Stroke Trial. AB - BACKGROUND AND PURPOSE: Asymptomatic hemorrhagic transformation of infarction (AHTI) is common, but its risk factors and relationship with functional outcome are poorly defined. METHODS: The analyses used data from the Tinzapararin in Acute Ischaemic Stroke Trial, a randomized controlled trial assessing tinzaparin (low molecular weight heparin) versus aspirin in 1484 patients with acute ischemic stroke. CT head scans (baseline, day 10) were adjudicated for the presence of hemorrhagic transformation. Stroke subtype was classified according to modified Trial of Org 10172 in Acute Stroke Treatment (small vessel, large vessel, cardioembolic) and the Oxfordshire Community Stroke Project (total anterior, partial anterior, lacunar, and posterior circulatory syndromes). Modified Rankin scale and Barthel Index were measured at 3 and 6 months. Analyses were adjusted for age, sex, severity, blood pressure, infarct volume, and treatment. Symptomatic hemorrhage was excluded. RESULTS: At day 10, AHTI did not differ between aspirin (300 mg; 32.8%) and medium-dose (100 IU/kg; 36.0%) and high-dose (175 IU/kg; 31.4%) tinzaparin groups (P = 0.44). Relative to lacunar stroke, AHTI on follow-up CT was significantly increased in total anterior circulation syndrome (odds ratio, 11.5; 95% CI, 7.1 to 18.7) and partial anterior circulation syndrome (odds ratio, 7.2; 95% CI, 4.5 to 11.4) stroke. Similarly, relative to small vessel disease, AHTI was increased in large vessel (odds ratio, 15.1; 95% CI, 9.4 to 24.3) and cardioembolic (odds ratio, 14.1; 95% CI, 8.5 to 23.5) stroke. After adjustment for infarct volume, the presence of AHTI was not associated with outcome at 3 or 6 months as measured by the modified Rankin Scale and Barthel Index. CONCLUSIONS: AHTI is increased in ischemic stroke with cortical syndromes and of large vessel or cardioembolic etiology. Heparin does not increase AHTI. AHTI is not associated with functional outcome. PMID- 21030713 TI - Interplay between heme oxygenase-1 and the multifunctional transcription factor yin yang 1 in the inhibition of intimal hyperplasia. AB - RATIONALE: induction of heme oxygenase (HO)-1 protects against experimental atherosclerotic diseases, and certain pharmacological HO-1 inducers, like probucol, inhibit the proliferation of vascular smooth muscle cells and, at the same time, promote the growth of endothelial cells in vivo and in vitro. OBJECTIVE: because such cell-specific effects are reminiscent of the action of the transcription factor Yin Yang (YY)1, we tested the hypothesis that there is a functional relationship between HO-1 and YY1. METHODS AND RESULTS: we report that probucol increases the number of YY1(+) cells in rat carotid artery following balloon injury at a time coinciding with increased HO-1 expression. The drug also induces the expression of YY1 mRNA and protein in rat aortic smooth muscle cells (RASMCs) in vitro, as do other known HO-1 inducers (tert-butylhydroquinone and hemin) and overexpression of HO-1 using a human HMOX1 cDNA plasmid. Conversely, overexpression of YY1 induces expression of HO-1 in RASMCs. Induction of YY1 expression is dependent on HO-1 enzyme activity and its reaction product CO, because pharmacological inhibition of heme oxygenase activity or CO scavenging block, whereas exposure of RASMCs to a CO-releasing molecule increases, YY1 expression. Furthermore, RNA interference knockdown of YY1 prevents probucol or adeno-HO-1 from inhibiting RASMC proliferation in vitro and neointimal formation in vivo. CONCLUSIONS: our findings show, for the first time, that HO-1 functionally interplays with the multifunctional transcription factor YY1 and that this interplay explains some of the protective activities of HO-1. PMID- 21030712 TI - RISC RNA sequencing for context-specific identification of in vivo microRNA targets. AB - RATIONALE: MicroRNAs (miRs) are expanding our understanding of cardiac disease and have the potential to transform cardiovascular therapeutics. One miR can target hundreds of individual mRNAs, but existing methodologies are not sufficient to accurately and comprehensively identify these mRNA targets in vivo. OBJECTIVE: To develop methods permitting identification of in vivo miR targets in an unbiased manner, using massively parallel sequencing of mouse cardiac transcriptomes in combination with sequencing of mRNA associated with mouse cardiac RNA-induced silencing complexes (RISCs). METHODS AND RESULTS: We optimized techniques for expression profiling small amounts of RNA without introducing amplification bias and applied this to anti-Argonaute 2 immunoprecipitated RISCs (RISC-Seq) from mouse hearts. By comparing RNA sequencing results of cardiac RISC and transcriptome from the same individual hearts, we defined 1645 mRNAs consistently targeted to mouse cardiac RISCs. We used this approach in hearts overexpressing miRs from Myh6 promoter-driven precursors (programmed RISC-Seq) to identify 209 in vivo targets of miR-133a and 81 in vivo targets of miR-499. Consistent with the fact that miR-133a and miR-499 have widely differing "seed" sequences and belong to different miR families, only 6 targets were common to miR-133a- and miR-499-programmed hearts. CONCLUSIONS: RISC-sequencing is a highly sensitive method for general RISC profiling and individual miR target identification in biological context and is applicable to any tissue and any disease state. PMID- 21030714 TI - Human CD34+/KDR+ cells are generated from circulating CD34+ cells after immobilization on activated platelets. AB - OBJECTIVE: The presence of kinase-insert domain-containing receptor (KDR) on circulating CD34+ cells is assumed to be indicative for the potential of these cells to support vascular maintenance and repair. However, in bone marrow and in granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood, less than 0.5% of CD34+ cells co-express KDR. Therefore, we studied whether CD34+/KDR+ cells are generated in the peripheral circulation. METHODS AND RESULTS: Using an ex vivo flow model, we show that activated platelets enable CD34+ cells to home to sites of vascular injury and that upon immobilization, KDR is translocated from an endosomal compartment to the cell-surface within 15 minutes. In patients with diabetes mellitus type 2, the percentage of circulating CD34+ co-expressing KDR was significantly elevated compared to age-matched controls. When treated with aspirin, the patients showed a 49% reduction in the generation of CD34+/KDR+ cells, indicating that the level of circulating CD34+/KDR+ cells also relates to in vivo platelet activation. CONCLUSIONS: Circulating CD34+/KDR+ are not mobilized from bone marrow as a predestined endothelial progenitor cell population but are mostly generated from circulating multipotent CD34+ cells at sites of vascular injury. Therefore, the number of circulating CD34+/KDR+ cells may serve as a marker for vascular injury. PMID- 21030717 TI - Intrapericardial, but not extrapericardial, fat is an independent predictor of impaired hyperemic coronary perfusion in coronary artery disease. AB - OBJECTIVE: To measure intrapericardial fat (IPF), extrapericardial fat (EPF), and myocardial perfusion (MBF) in patients with and without coronary artery disease (CAD), hypothesizing that perfusion is more strongly associated with IPF because it is in direct anatomic contiguity with the myocardium or coronary arteries. METHODS AND RESULTS: Fat surrounding the heart may increase the risk of CAD and calcification, but little is known about the role of MBF in this relationship. The study included 107 patients with an intermediate likelihood of CAD. Positron emission tomography/computed tomography was used to measure IPF and EPF volumes and coronary artery calcium level, together with MBF at rest and during adenosine induced hyperemia. Subsequently, all subjects underwent coronary angiography and were grouped for presence/absence of CAD and severity of myocardial hypoperfusion. IPF and EPF levels were higher in men and in patients with CAD (n=85) than in those without CAD (n=22) (P<0.001). EPF was increased regardless of the degree of stenoses (n=45), whereas IPF was selectively increased in subjects with obstructive stenoses (n=40). IPF and EPF levels were both associated with coronary artery calcium scores (R=0.25 and R=0.26, respectively; P<0.02), coronary flow reserve (R=-0.37 and R=-0.38, respectively; P<0.001), and hyperemic MBF (R=-0.36 and R=-0.44, respectively; P<0.0005). Male sex was a strong negative predictor of MBF. After discounting for confounders, myocardial hyperemic perfusion was predicted independently by sex, coronary artery calcium score, and IPF, but not EPF. CONCLUSIONS: CAD is accompanied by augmented fat depots surrounding the heart, which are negatively related to coronary flow hyperemia. Among fat depots, IPF was the only independent predictor of hyperemic MBF, supporting the hypothesis of a direct paracrine/vasocrine effect. PMID- 21030715 TI - Macrophage adipose triglyceride lipase deficiency attenuates atherosclerotic lesion development in low-density lipoprotein receptor knockout mice. AB - OBJECTIVE: The consequences of macrophage triglyceride (TG) accumulation on atherosclerosis have not been studied in detail so far. Adipose triglyceride lipase (ATGL) is the rate-limiting enzyme for the initial step in TG hydrolysis. Because ATGL knockout (KO) mice exhibit massive TG accumulation in macrophages, we used ATGL KO mice to study the effects of macrophage TG accumulation on atherogenesis. METHODS AND RESULTS: Low-density lipoprotein receptor (LDLr) KO mice were transplanted with bone marrow from ATGL KO (ATGL KO->LDLr KO) or wild type (WT->LDLr KO) mice and challenged with a Western-type diet for 9 weeks. Despite TG accumulation in ATGL KO macrophages, atherosclerosis in ATGL KO->LDLr KO mice was 43% reduced associated with decreased plasma monocyte chemoattractant protein-1 (MCP-1) and macrophage interleukin-6 concentrations. This coincided with a reduced amount of macrophages, possibly because of a 39% increase in intraplaque apoptosis and a decreased migratory capacity of ATGL KO macrophages. The reduced number of white blood cells might be due to a 36% decreased Lin(-)Sca 1(+)cKit(+) hematopoietic stem cell population. CONCLUSIONS: We conclude that the attenuation of atherogenesis in ATGL KO->LDLr KO mice is due to decreased infiltration of less inflammatory macrophages into the arterial wall and increased macrophage apoptosis. PMID- 21030716 TI - CD11c/CD18 expression is upregulated on blood monocytes during hypertriglyceridemia and enhances adhesion to vascular cell adhesion molecule-1. AB - OBJECTIVE: Atherosclerosis is associated with monocyte adhesion to the arterial wall that involves integrin activation and emigration across inflamed endothelium. Involvement of beta(2)-integrin CD11c/CD18 in atherogenesis was recently shown in dyslipidemic mice, which motivates our study of its inflammatory function during hypertriglyceridemia in humans. METHODS AND RESULTS: Flow cytometry of blood from healthy subjects fed a standardized high-fat meal revealed that at 3.5 hours postprandial, monocyte CD11c surface expression was elevated, and the extent of upregulation correlated with blood triglycerides. Monocytes from postprandial blood exhibited an increased light scatter profile, which correlated with elevated CD11c expression and uptake of lipid particles. Purified monocytes internalized triglyceride-rich lipoproteins isolated from postprandial blood through low-density lipoprotein-receptor-related protein-1, and this also elicited CD11c upregulation. Laboratory-on-a-chip analysis of whole blood showed that monocyte arrest on a vascular cell adhesion molecule-1 (VCAM-1) substrate under shear flow was elevated at 3.5 hours and correlated with blood triglyceride and CD11c expression. At 7 hours postprandial, blood triglycerides decreased and monocyte CD11c expression and arrest on VCAM-1 returned to fasting levels. CONCLUSIONS: During hypertriglyceridemia, monocytes internalize lipids, upregulate CD11c, and increase adhesion to VCAM-1. These data suggest that analysis of monocyte inflammation may provide an additional framework for evaluating individual susceptibility to cardiovascular disease. PMID- 21030720 TI - A reliable recipe for heart cells? AB - Deepak Srivastava's group at the Gladstone Institute of Cardiovascular Disease, University of California San Francisco, reported in the August 6 issue of the journal Cell that to make heart muscle cells, all you need are three factors and some fibroblasts. But is it really that easy? PMID- 21030718 TI - Cellular and molecular changes associated with inhibitory effect of pioglitazone on neointimal growth in patients with type 2 diabetes after zotarolimus-eluting stent implantation. AB - OBJECTIVE: To investigate the mechanistic basis underlying antirestenosis and the antiatherogenic effect of pioglitazone in patients with type 2 diabetes mellitus who were undergoing zotarolimus-eluting stent implantation. METHODS AND RESULTS: Recent studies highlight the beneficial effect of pioglitazone in attenuating neointimal growth after stent implantation. Patients with coronary artery diseases were randomly assigned to pioglitazone (n=47) or placebo (n=47) after stent implantation. Pioglitazone significantly reduced neointimal hyperplasia within the stented lesion and attenuated total plaque burden in the in-segment regions of the stent, as assessed by intravascular ultrasonography at the 8-month follow-up. These changes were preceded by reduced circulating natural killer (NK) cells, diminished interleukin 6 and monocyte chemoattractant protein-1 levels, and downregulation of chemokine receptor 2 at 2 days after stent implantation; and an elevated interleukin 10 level at 10 days after implantation. Furthermore, the proliferation and migration of vascular smooth muscle cells were inhibited in the presence of pioglitazone-treated patient serum, demonstrating that the antiproliferative effects of pioglitazone occurred concurrently with its antiinflammatory action. CONCLUSIONS: Our data present early cellular and immunologic changes by pioglitazone that might have been associated with antirestenotic and antiatherogenic effects in diabetic patients. Inhibiting proinflammatory responses while promoting antiinflammatory circuits, together with an antiproliferative action, may, in part, account for the antirestenotic effect of pioglitazone by altering vascular remodeling processes in the early phase. PMID- 21030721 TI - CaMKII inhibition in heart failure makes jump to human. PMID- 21030722 TI - Microparticles: protagonists of a novel communication network for intercellular information exchange. AB - Microparticles represent a heterogeneous population of vesicles with a diameter of 100 to 1000 nm that are released by budding of the plasma membrane and express antigens specific of their parental cells. Although microparticle formation represents a physiological phenomenon, a multitude of pathologies are associated with a considerable increase in circulating microparticles, including inflammatory and autoimmune diseases, atherosclerosis, and malignancies. Microparticles display an broad spectrum of bioactive substances and receptors on their surface and harbor a concentrated set of cytokines, signaling proteins, mRNA, and microRNA. Recent studies provided evidence for the concept of microparticles as veritable vectors for the intercellular exchange of biological signals and information. Indeed, microparticles may transfer part of their components and content to selected target cells, thus mediating cell activation, phenotypic modification, and reprogramming of cell function. Because microparticles readily circulate in the vasculature, they may serve as shuttle modules and signaling transducers not only in their local environment but also at remarkable distance from their site of origin. Altogether, this transcellular delivery system may extend the confines of the limited transcriptome and proteome of recipient cells and establishes a communication network in which specific properties and information among cells can be efficiently shared. At least in same cases, the sequential steps of the transfer process underlie complex regulatory mechanisms, including selective sorting ("packaging") of microparticle components and content, specificity of interactions with target cells determined by surface receptors, and ultimately finely tuned and signal-dependent release and delivery of microparticle content. PMID- 21030724 TI - Endoplasmic reticulum stress as a therapeutic target in cardiovascular disease. AB - Cardiovascular disease constitutes a major and increasing health burden in developed countries. Although treatments have progressed, the development of novel treatments for patients with cardiovascular diseases remains a major research goal. The endoplasmic reticulum (ER) is the cellular organelle in which protein folding, calcium homeostasis, and lipid biosynthesis occur. Stimuli such as oxidative stress, ischemic insult, disturbances in calcium homeostasis, and enhanced expression of normal and/or folding-defective proteins lead to the accumulation of unfolded proteins, a condition referred to as ER stress. ER stress triggers the unfolded protein response (UPR) to maintain ER homeostasis. The UPR involves a group of signal transduction pathways that ameliorate the accumulation of unfolded protein by increasing ER-resident chaperones, inhibiting protein translation and accelerating the degradation of unfolded proteins. The UPR is initially an adaptive response but, if unresolved, can lead to apoptotic cell death. Thus, the ER is now recognized as an important organelle in deciding cell life and death. There is compelling evidence that the adaptive and proapoptotic pathways of UPR play fundamental roles in the development and progression of cardiovascular diseases, including heart failure, ischemic heart diseases, and atherosclerosis. Thus, therapeutic interventions that target molecules of the UPR component and reduce ER stress will be promising strategies to treat cardiovascular diseases. In this review, we summarize the recent progress in understanding UPR signaling in cardiovascular disease and its related therapeutic potential. Future studies may clarify the most promising molecules to be investigated as targets for cardiovascular diseases. PMID- 21030726 TI - Content validation of a standardized algorithm for ostomy care. AB - The number of ostomy care clinician experts is limited and the majority of ostomy care is provided by non-specialized clinicians or unskilled caregivers and family. The purpose of this study was to obtain content validation data for a new standardized algorithm for ostomy care developed by expert wound ostomy continence nurse (WOCN) clinicians. After face validity was established using overall review and suggestions from WOCN experts, 166 WOCNs self-identified as having expertise in ostomy care were surveyed online for 6 weeks in 2009. Using a cross-sectional, mixed methods study design and a 30-item instrument with a 4 point Likert-type scale, the participants were asked to quantify the degree of validity of the Ostomy Algorithm's decisions and components. Participants' open ended comments also were thematically analyzed. Using a scale of 1 to 4, the mean score of the entire algorithm was 3.8 (4 = relevant/very relevant). The algorithm's content validity index (CVI) was 0.95 (out of 1.0). Individual component mean scores ranged from 3.59 to 3.91. Individual CVIs ranged from 0.90 to 0.98. Qualitative data analysis revealed themes of difficulty associated with algorithm formatting, especially orientation and use of the Studio Alterazioni Cutanee Stomali (Study on Peristomal Skin Lesions [SACSTM Instrument]) and the inability of algorithms to capture all individual patient attributes affecting ostomy care. Positive themes included content thoroughness and the helpful clinical photos. Suggestions were offered for algorithm improvement. Study results support the strong content validity of the algorithm and research to ascertain its construct validity and effect on care outcomes is warranted. PMID- 21030725 TI - Urban air pollution targets the dorsal vagal complex and dark chocolate offers neuroprotection. AB - Mexico City (MC) residents exposed to fine particulate matter and endotoxin exhibit inflammation of the olfactory bulb, substantia nigra, and vagus nerve. The goal of this study was to model these endpoints in mice and examine the neuroprotective effects of chocolate. Mice exposed to MC air received no treatment or oral dark chocolate and were compared to clean-air mice either untreated or treated intraperitoneally with endotoxin. Cyclooxygenase-2 (COX-2), interleukin 1 beta (IL-1beta), and CD14 messenger RNA (mRNA) were quantified after 4, 8, and 16 months of exposure in target brain regions. After 16 months of exposure, the dorsal vagal complex (DVC) exhibited significant inflammation in endotoxin-treated and MC mice (COX-2 and IL-1beta P<.001). Mexico City mice had olfactory bulb upregulation of CD14 (P=.002) and significant DVC imbalance in genes for antioxidant defenses, apoptosis, and neurodegeneration. These findings demonstrate sustained DVC inflammation in mice exposed to MC air, which is mitigated by chocolate administration. PMID- 21030723 TI - Oxidative stress and diabetic complications. AB - Oxidative stress plays a pivotal role in the development of diabetes complications, both microvascular and cardiovascular. The metabolic abnormalities of diabetes cause mitochondrial superoxide overproduction in endothelial cells of both large and small vessels, as well as in the myocardium. This increased superoxide production causes the activation of 5 major pathways involved in the pathogenesis of complications: polyol pathway flux, increased formation of AGEs (advanced glycation end products), increased expression of the receptor for AGEs and its activating ligands, activation of protein kinase C isoforms, and overactivity of the hexosamine pathway. It also directly inactivates 2 critical antiatherosclerotic enzymes, endothelial nitric oxide synthase and prostacyclin synthase. Through these pathways, increased intracellular reactive oxygen species (ROS) cause defective angiogenesis in response to ischemia, activate a number of proinflammatory pathways, and cause long-lasting epigenetic changes that drive persistent expression of proinflammatory genes after glycemia is normalized ("hyperglycemic memory"). Atherosclerosis and cardiomyopathy in type 2 diabetes are caused in part by pathway-selective insulin resistance, which increases mitochondrial ROS production from free fatty acids and by inactivation of antiatherosclerosis enzymes by ROS. Overexpression of superoxide dismutase in transgenic diabetic mice prevents diabetic retinopathy, nephropathy, and cardiomyopathy. The aim of this review is to highlight advances in understanding the role of metabolite-generated ROS in the development of diabetic complications. PMID- 21030727 TI - The effect of nonweight-bearing exercise and protocol adherence on diabetic foot ulcer healing: a pilot study. AB - I nnovative approaches to the prevention and treatment of foot wounds in persons with diabetes mellitus are needed and preliminary research suggests that exercise therapy may increase joint mobility and blood flow. A 12-week, prospective, quasi experimental pilot study was conducted to evaluate the potential influence of nonweight-bearing ankle exercises, and adherence to same, on the size of neuropathic, diabetic foot wounds in community-dwelling older adults. Nineteen patients were recruited. Of those, 10 (88.9% men) were randomized to ankle exercise treatments and nine (50% men) continued their previous care regimen. Patients randomized to the exercise program were younger and had smaller wounds than those in the control group (average age 62.2 +/- 8.54 versus 74.25 +/- 16.25 years and measurement 0.94 cm2 +/- 1.89 versus 2.53 cm2 +/- 3.647, respectively). Thirty percent (30%) of the patients in the exercise and 33.3% in the control group healed. The percent wound reduction between groups was not significantly different (Mann Whitney U test, P = .696). Adherence to the recommended exercise program was variable but 70% performed some exercises. The results of this pilot study provide important lessons for future studies, including the need to enroll more patients and provide more exercise guidance. Considering the increasing prevalence of diabetes mellitus and resultant complications, as well as the potential benefits of this non-invasive treatment regimen, larger studies are warranted. PMID- 21030729 TI - Pressure ulcer knowledge among nurses in a Brazilian university hospital. AB - To facilitate the implementation of evidence-based skin and pressure ulcer (PU) care practices and related staff education programs in a university hospital in Brazil, a cross-sectional study was conducted to evaluate nurses' knowledge about PU prevention, wound assessment, and staging. Of the 141 baccalaureate nurses (BSN) employed by the hospital at the time of the study, 106 consented to participate. Using a Portuguese version of Pieper's Pressure Ulcer Knowledge Test (PUKT), participants were asked to indicate whether 33 statements about PU prevention and eight about PU assessment and staging were true or false. For the 33 prevention statements, the average number answered correctly was 26.07 (SD 4.93) and for the eight assessment statements the average was 4.59 (SD 1.62). Nurses working on inpatient clinical nursing units had significantly better scores (P = 0.000). Years of nursing experience had a weak and negative correlation with correct PUKT scores (r = -0.21, P = 0.033) as did years of experience working in the university hospital (r = -.179, P <.071). Incorrect responses were most common for statements related to patient positioning, massage, PU assessment, and staging definitions. The results of this study confirm that nurses have an overall understanding of PU prevention and assessment principles but important knowledge deficits exist. Focused continuing education efforts are needed to facilitate the implementation of evidence-based care. PMID- 21030728 TI - Prevalence of pressure ulcers in a Brazilian hospital: results of a cross sectional study. AB - Technological advances in recent decades have extended survival time of critically ill hospitalized patients but their unstable physiological state and limited mobility increase their risk for pressure ulcers. On two different days (June 16 and October 20, 2004), pressure ulcer prevalence in patients hospitalized at the Sao Paulo Hospital, Brazil was assessed. On study day 1, 43 of the 376 inpatients (prevalence, 11.4%) and on study day 2, 35 of 340 inpatients (prevalence, 10.3%) had pressure ulcers. No significant differences in patient or ulcer characteristics between the two study days were observed. Ulcer prevalence was highest among patients in the intensive care unit (average 32.7%). Most patients had one ulcer (61.5%), classified as Stage II (47%), located in the sacral area (47%), and were considered at high risk according to their Braden Scale scores (60% had a score <= 11). The results obtained were not unexpected and confirmed the need to improve quality of care by establishing pressure ulcer prevention protocols. Additional studies to optimize prevention efforts and improve the existing evidence-base are necessary, especially in patient care units with high pressure ulcer rates. PMID- 21030730 TI - Exact computation of coalescent likelihood for panmictic and subdivided populations under the infinite sites model. AB - Coalescent likelihood is the probability of observing the given population sequences under the coalescent model. Computation of coalescent likelihood under the infinite sites model is a classic problem in coalescent theory. Existing methods are based on either importance sampling or Markov chain Monte Carlo and are inexact. In this paper, we develop a simple method that can compute the exact coalescent likelihood for many data sets of moderate size, including real biological data whose likelihood was previously thought to be difficult to compute exactly. Our method works for both panmictic and subdivided populations. Simulations demonstrate that the practical range of exact coalescent likelihood computation for panmictic populations is significantly larger than what was previously believed. We investigate the application of our method in estimating mutation rates by maximum likelihood. A main application of the exact method is comparing the accuracy of approximate methods. To demonstrate the usefulness of the exact method, we evaluate the accuracy of program Genetree in computing the likelihood for subdivided populations. PMID- 21030731 TI - A sparse learning machine for high-dimensional data with application to microarray gene analysis. AB - Extracting features from high-dimensional data is a critically important task for pattern recognition and machine learning applications. High-dimensional data typically have much more variables than observations, and contain significant noise, missing components, or outliers. Features extracted from high-dimensional data need to be discriminative, sparse, and can capture essential characteristics of the data. In this paper, we present a way to constructing multivariate features and then classify the data into proper classes. The resulting small subset of features is nearly the best in the sense of Greenshtein's persistence; however, the estimated feature weights may be biased. We take a systematic approach for correcting the biases. We use conjugate gradient-based primal-dual interior-point techniques for large-scale problems. We apply our procedure to microarray gene analysis. The effectiveness of our method is confirmed by experimental results. PMID- 21030732 TI - A survey of spatial defects in Homo Sapiens Affymetrix GeneChips. AB - Modern biology has moved from a science of individual measurements to a science where data are collected on an industrial scale. Foremost, among the new tools for biochemistry are chip arrays which, in one operation, measure hundreds of thousands or even millions of DNA sequences or RNA transcripts. While this is impressive, increasingly sophisticated analysis tools have been required to convert gene array data into gene expression levels. Despite the assumption that noise levels are low, since the number of measurements for an individual gene is small, identifying which signals are affected by noise is a priority. High density oligonucleotide array (HDONAs) from NCBI GEO shows that, even in the best Human GeneChips 1/4 percent of data are affected by spatial noise. Earlier designs are noisier and spatial defects may affect more than 25 percent of probes. BioConductor R code is available as supplementary material which can be found on the Computer Society Digital Library at http://doi.ieeecomputersociety.org/10.1109/TCBB.2008.108 and via http://bioinformatics.essex.ac.uk/users/wlangdon/TCBB-2007-11-0161.tar.gz. PMID- 21030733 TI - A cluster refinement algorithm for motif discovery. AB - Finding Transcription Factor Binding Sites, i.e., motif discovery, is crucial for understanding the gene regulatory relationship. Motifs are weakly conserved and motif discovery is an NP-hard problem. We propose a new approach called Cluster Refinement Algorithm for Motif Discovery (CRMD). CRMD employs a flexible statistical motif model allowing a variable number of motifs and motif instances. CRMD first uses a novel entropy-based clustering to find complete and good starting candidate motifs from the DNA sequences. CRMD then employs an effective greedy refinement to search for optimal motifs from the candidate motifs. The refinement is fast, and it changes the number of motif instances based on the adaptive thresholds. The performance of CRMD is further enhanced if the problem has one occurrence of motif instance per sequence. Using an appropriate similarity test of motifs, CRMD is also able to find multiple motifs. CRMD has been tested extensively on synthetic and real data sets. The experimental results verify that CRMD usually outperforms four other state-of-the-art algorithms in terms of the qualities of the solutions with competitive computing time. It finds a good balance between finding true motif instances and screening false motif instances, and is robust on problems of various levels of difficulty. PMID- 21030734 TI - Finding the nearest neighbors in biological databases using less distance computations. AB - Modern biological applications usually involve the similarity comparison between two objects, which is often computationally very expensive, such as whole genome pairwise alignment and protein 3D structure alignment. Nevertheless, being able to quickly identify the closest neighboring objects from very large databases for a newly obtained sequence or structure can provide timely hints to its functions and more. This paper presents a substantial speedup technique for the well studied k-nearest neighbor (k-nn) search, based on novel concepts of virtual pivots and partial pivots, such that a significant number of the expensive distance computations can be avoided. The new method is able to dynamically locate virtual pivots, according to the query, with increasing pruning ability. Using the same or less amount of database preprocessing effort, the new method outperformed the second best method by using no more than 40 percent distance computations per query, on a database of 10,000 gene sequences, compared to several best known k-nn search methods including M-Tree, OMNI, SA-Tree, and LAESA. We demonstrated the use of this method on two biological sequence data sets, one of which is for HIV-1 viral strain computational genotyping. PMID- 21030735 TI - Human-readable rule generator for integrating amino scid sequence information and stability of mutant proteins. AB - Most of the bioinformatics tools developed for predicting mutant protein stability appear as a black box and the relationship between amino acid sequence/structure and stability is hidden to the users. We have addressed this problem and developed a human-readable rule generator for integrating the knowledge of amino acid sequence and experimental stability change upon single mutation. Using information about the original residue, substituted residue, and three neighboring residues, classification rules have been generated to discriminate the stabilizing and destabilizing mutants and explore the basis for experimental data. These rules are human readable, and hence, the method enhances the synergy between expert knowledge and computational system. Furthermore, the performance of the rules has been assessed on a nonredundant data set of 1,859 mutants and we obtained an accuracy of 80 percent using cross validation. The results showed that the method could be effectively used as a tool for both knowledge discovery and predicting mutant protein stability. We have developed a Web for classification rule generator and it is freely available at http://bioinformatics.myweb.hinet.net/irobot.htm. PMID- 21030736 TI - Quantifying the degree of self-nestedness of trees: application to the structural analysis of plants. AB - In this paper, we are interested in the problem of approximating trees by trees with a particular self-nested structure. Self-nested trees are such that all their subtrees of a given height are isomorphic. We show that these trees present remarkable compression properties, with high compression rates. In order to measure how far a tree is from being a self-nested tree, we then study how to quantify the degree of self-nestedness of any tree. For this, we define a measure of the self-nestedness of a tree by constructing a self-nested tree that minimizes the distance of the original tree to the set of self-nested trees that embed the initial tree. We show that this measure can be computed in polynomial time and depict the corresponding algorithm. The distance to this nearest embedding self-nested tree (NEST) is then used to define compression coefficients that reflect the compressibility of a tree. To illustrate this approach, we then apply these notions to the analysis of plant branching structures. Based on a database of simulated theoretical plants in which different levels of noise have been introduced, we evaluate the method and show that the NESTs of such branching structures restore partly or completely the original, noiseless, branching structures. The whole approach is then applied to the analysis of a real plant (a rice panicle) whose topological structure was completely measured. We show that the NEST of this plant may be interpreted in biological terms and may be used to reveal important aspects of the plant growth. PMID- 21030737 TI - Quartets MaxCut: a divide and conquer quartets algorithm. AB - Accurate phylogenetic reconstruction methods are currently limited to a maximum of few dozens of taxa. Supertree methods construct a large tree over a large set of taxa, from a set of small trees over overlapping subsets of the complete taxa set. Hence, in order to construct the tree of life over a million and a half different species, the use of a supertree method over the product of accurate methods, is inevitable. Perhaps the simplest version of this task that is still widely applicable, yet quite challenging, is quartet-based reconstruction. This problem lies at the root of many tree reconstruction methods and theoretical as well as experimental results have been reported. Nevertheless, dealing with false, conflicting quartet trees remains problematic. In this paper, we describe an algorithm for constructing a tree from a set of input quartet trees even with a significant fraction of errors. We show empirically that conflicts in the inputs are handled satisfactorily and that it significantly outperforms and outraces the Matrix Representation with Parsimony (MRP) methods that have previously been most successful in dealing with supertrees. Our algorithm is based on a divide and conquer algorithm where our divide step uses a semidefinite programming (SDP) formulation of MaxCut. We remark that this builds on previous work of ours for piecing together trees from rooted triplet trees. The recursion for unrooted quartets, however, is more complicated in that even with completely consistent set of quartet trees the problem is NP-hard, as opposed to the problem for triples where there is a linear time algorithm. This complexity leads to several issues and some solutions of possible independent interest. PMID- 21030738 TI - RDCurve: a nonparametric method to evaluate the stability of ranking procedures. AB - Great concerns have been raised about the reproducibility of gene signatures based on high-throughput techniques such as microarray. Studies analyzing similar samples often report poorly overlapping results, and the p-value usually lacks biological context. We propose a nonparametric ReDiscovery Curve (RDCurve) method, to estimate the frequency of rediscovery of gene signature identified. Given a ranking procedure and a data set with replicated measurements, the RDCurve bootstraps the data set and repeatedly applies the ranking procedure, selects a subset of k important genes, and estimates the probability of rediscovery of the selected subset of genes. We also propose a permutation scheme to estimate the confidence band under the Null hypothesis for the significance of the RDCurve. The method is nonparametric and model-independent. With the RDCurve, we can assess the signal-to-noise ratio of the data, compare the performance of ranking procedures in term of their expected rediscovery rates, and choose the number of genes to be reported. PMID- 21030739 TI - SARNA-Predict: accuracy improvement of RNA secondary structure prediction using permutation-based simulated annealing. AB - Ribonucleic acid (RNA), a single-stranded linear molecule, is essential to all biological systems. Different regions of the same RNA strand will fold together via base pair interactions to make intricate secondary and tertiary structures that guide crucial homeostatic processes in living organisms. Since the structure of RNA molecules is the key to their function, algorithms for the prediction of RNA structure are of great value. In this article, we demonstrate the usefulness of SARNA-Predict, an RNA secondary structure prediction algorithm based on Simulated Annealing (SA). A performance evaluation of SARNA-Predict in terms of prediction accuracy is made via comparison with eight state-of-the-art RNA prediction algorithms: mfold, Pseudoknot (pknotsRE), NUPACK, pknotsRG-mfe, Sfold, HotKnots, ILM, and STAR. These algorithms are from three different classes: heuristic, dynamic programming, and statistical sampling techniques. An evaluation for the performance of SARNA-Predict in terms of prediction accuracy was verified with native structures. Experiments on 33 individual known structures from eleven RNA classes (tRNA, viral RNA, antigenomic HDV, telomerase RNA, tmRNA, rRNA, RNaseP, 5S rRNA, Group I intron 23S rRNA, Group I intron 16S rRNA, and 16S rRNA) were performed. The results presented in this paper demonstrate that SARNA-Predict can out-perform other state-of-the-art algorithms in terms of prediction accuracy. Furthermore, there is substantial improvement of prediction accuracy by incorporating a more sophisticated thermodynamic model (efn2). PMID- 21030740 TI - Using Gaussian process with test rejection to detect T-cell epitopes in pathogen genomes. AB - A major challenge in the development of peptide-based vaccines is finding the right immunogenic element, with efficient and long-lasting immunization effects, from large potential targets encoded by pathogen genomes. Computer models are convenient tools for scanning pathogen genomes to preselect candidate immunogenic peptides for experimental validation. Current methods predict many false positives resulting from a low prevalence of true positives. We develop a test reject method based on the prediction uncertainty estimates determined by Gaussian process regression. This method filters false positives among predicted epitopes from a pathogen genome. The performance of stand-alone Gaussian process regression is compared to other state-of-the-art methods using cross validation on 11 benchmark data sets. The results show that the Gaussian process method has the same accuracy as the top performing algorithms. The combination of Gaussian process regression with the proposed test reject method is used to detect true epitopes from the Vaccinia virus genome. The test rejection increases the prediction accuracy by reducing the number of false positives without sacrificing the method's sensitivity. We show that the Gaussian process in combination with test rejection is an effective method for prediction of T-cell epitopes in large and diverse pathogen genomes, where false positives are of concern. PMID- 21030741 TI - VARUN: discovering extensible motifs under saturation constraints. AB - The discovery of motifs in biosequences is frequently torn between the rigidity of the model on one hand and the abundance of candidates on the other hand. In particular, motifs that include wild cards or "don't cares" escalate exponentially with their number, and this gets only worse if a don't care is allowed to stretch up to some prescribed maximum length. In this paper, a notion of extensible motif in a sequence is introduced and studied, which tightly combines the structure of the motif pattern, as described by its syntactic specification, with the statistical measure of its occurrence count. It is shown that a combination of appropriate saturation conditions and the monotonicity of probabilistic scores over regions of constant frequency afford us significant parsimony in the generation and testing of candidate overrepresented motifs. A suite of software programs called Varun is described, implementing the discovery of extensible motifs of the type considered. The merits of the method are then documented by results obtained in a variety of experiments primarily targeting protein sequence families. Of equal importance seems the fact that the sets of all surprising motifs returned in each experiment are extracted faster and come in much more manageable sizes than would be obtained in the absence of saturation constraints. PMID- 21030742 TI - The Metropolized Partial Importance Sampling MCMC mixes slowly on minimum reversal rearrangement paths. AB - Markov chain Monte Carlo has been the standard technique for inferring the posterior distribution of genome rearrangement scenarios under a Bayesian approach. We present here a negative result on the rate of convergence of the generally used Markov chains. We prove that the relaxation time of the Markov chains walking on the optimal reversal sorting scenarios might grow exponentially with the size of the signed permutations, namely, with the number of syntheny blocks. PMID- 21030743 TI - An enhanced high-resolution EMCCD-based gamma camera using SiPM side detection. AB - Electron-multiplying charge-coupled devices (EMCCDs) coupled to scintillation crystals can be used for high-resolution imaging of gamma rays in scintillation counting mode. However, the detection of false events as a result of EMCCD noise deteriorates the spatial and energy resolution of these gamma cameras and creates a detrimental background in the reconstructed image. In order to improve the performance of an EMCCD-based gamma camera with a monolithic scintillation crystal, arrays of silicon photon-multipliers (SiPMs) can be mounted on the sides of the crystal to detect escaping scintillation photons, which are otherwise neglected. This will provide a priori knowledge about the correct number and energies of gamma interactions that are to be detected in each CCD frame. This information can be used as an additional detection criterion, e.g. for the rejection of otherwise falsely detected events. The method was tested using a gamma camera based on a back-illuminated EMCCD, coupled to a 3 mm thick continuous CsI:Tl crystal. Twelve SiPMs have been mounted on the sides of the CsI:Tl crystal. When the information of the SiPMs is used to select scintillation events in the EMCCD image, the background level for (99m)Tc is reduced by a factor of 2. Furthermore, the SiPMs enable detection of (125)I scintillations. A hybrid SiPM-/EMCCD-based gamma camera thus offers great potential for applications such as in vivo imaging of gamma emitters. PMID- 21030744 TI - A unified framework for 3D radiation therapy and IMRT planning: plan optimization in the beamlet domain by constraining or regularizing the fluence map variations. AB - The purpose of this work is to demonstrate that physical constraints on fluence gradients in 3D radiation therapy (RT) planning can be incorporated into beamlet optimization explicitly by direct constraint on the spatial variation of the fluence maps or implicitly by using total-variation regularization (TVR). The former method forces the fluence to vary in accordance with the known form of a wedged field and latter encourages the fluence to take the known form of the wedged field by requiring the derivatives of the fluence maps to be piece-wise constant. The performances of the proposed methods are evaluated by using a brain cancer case and a head and neck case. It is found that both approaches are capable of providing clinically sensible 3D RT solutions with monotonically varying fluence maps. For currently available 3D RT delivery schemes based on the use of customized physical or dynamic wedges, constrained optimization seems to be more useful because the optimized fields are directly deliverable. Working in the beamlet domain provides a natural way to model the spatial variation of the beam fluence. The proposed methods take advantage of the fact that 3D RT is a special form of intensity-modulated radiation therapy (IMRT) and finds the optimal plan by searching for fields with a certain type of spatial variation. The approach provides a unified framework for 3D CRT and IMRT plan optimization. PMID- 21030745 TI - A CT-based software tool for evaluating compensator quality in passively scattered proton therapy. AB - We have developed a quantitative computed tomography (CT)-based quality assurance (QA) tool for evaluating the accuracy of manufactured compensators used in passively scattered proton therapy. The thickness of a manufactured compensator was measured from its CT images and compared with the planned thickness defined by the treatment planning system. The difference between the measured and planned thicknesses was calculated with use of the Euclidean distance transformation and the kd-tree search method. Compensator accuracy was evaluated by examining several parameters including mean distance, maximum distance, global thickness error and central axis shifts. Two rectangular phantoms were used to validate the performance of the QA tool. Nine patients and 20 compensators were included in this study. We found that mean distances, global thickness errors and central axis shifts were all within 1 mm for all compensators studied, with maximum distances ranging from 1.1 to 3.8 mm. Although all compensators passed manual verification at selected points, about 5% of the pixels still had maximum distances of >2 mm, most of which correlated with large depth gradients. The correlation between the mean depth gradient of the compensator and the percentage of pixels with mean distance <1 mm is -0.93 with p < 0.001, which suggests that the mean depth gradient is a good indicator of compensator complexity. These results demonstrate that the CT-based compensator QA tool can be used to quantitatively evaluate manufactured compensators. PMID- 21030747 TI - Treatment planning for a scanned carbon beam with a modified microdosimetric kinetic model. AB - We describe a method to calculate the relative biological effectiveness in mixed radiation fields of therapeutic ion beams based on the modified microdosimetric kinetic model (modified MKM). In addition, we show the procedure for integrating the modified MKM into a treatment planning system for a scanned carbon beam. With this procedure, the model is fully integrated into our research version of the treatment planning system. To account for the change in radiosensitivity of a cell line, we measured one of the three MKM parameters from a single survival curve of the current cells and used the parameter in biological optimization. Irradiation of human salivary gland tumor cells was performed with a scanned carbon beam in the Heavy Ion Medical Accelerator in Chiba (HIMAC), and we then compared the measured depth-survival curve with the modified MKM predicted survival curve. Good agreement between the two curves proves that the proposed method is a candidate for calculating the biological effects in treatment planning for ion irradiation. PMID- 21030746 TI - Effects of frequency- and direction-dependent elastic materials on linearly elastic MRE image reconstructions. AB - The mechanical model commonly used in magnetic resonance elastography (MRE) is linear elasticity. However, soft tissue may exhibit frequency- and direction dependent (FDD) shear moduli in response to an induced excitation causing a purely linear elastic model to provide an inaccurate image reconstruction of its mechanical properties. The goal of this study was to characterize the effects of reconstructing FDD data using a linear elastic inversion (LEI) algorithm. Linear and FDD phantoms were manufactured and LEI images were obtained from time harmonic MRE acquisitions with variations in frequency and driving signal amplitude. LEI responses to artificially imposed uniform phase shifts in the displacement data from both purely linear elastic and FDD phantoms were also evaluated. Of the variety of FDD phantoms considered, LEI appeared to tolerate viscoelastic data-model mismatch better than deviations caused by poroelastic and anisotropic mechanical properties in terms of visual image contrast. However, the estimated shear modulus values were substantially incorrect relative to independent mechanical measurements even in the successful viscoelastic cases and the variations in mean values with changes in experimental conditions associated with uniform phase shifts, driving signal frequency and amplitude were unpredictable. Overall, use of LEI to reconstruct data acquired in phantoms with FDD material properties provided biased results under the best conditions and significant artifacts in the worst cases. These findings suggest that the success with which LEI is applied to MRE data in tissue will depend on the underlying mechanical characteristics of the tissues and/or organs systems of clinical interest. PMID- 21030748 TI - AB-OSEM reconstruction for improved Patlak kinetic parameter estimation: a simulation study. AB - The non-negativity constraint inherently present in OSEM reconstruction successfully reduces the standard deviation in cold regions but at the cost of introducing a positive bias, especially at low iteration numbers. For low-count data, as often encountered in short-duration frames in dynamic imaging protocols, it has been shown that it can be advantageous (in terms of bias in the reconstructed image) to remove the non-negativity constraint. In this work two competing algorithms that do not impose non-negativity in the reconstructed image are investigated: NEG-ML and AB-OSEM. It was found that the AB-OSEM reconstruction outperformed the NEG-ML reconstruction. The AB-OSEM algorithm was then further developed to allow a forward model that includes randoms and scatter background terms. In addition to static reconstruction the current analysis was extended to consider the important case of kinetic parameter estimation from dynamic PET data. Simulation studies (comparing OSEM, FBP and AB-OSEM) showed that the positive bias obtained with OSEM reconstruction can be avoided in both static and parametric imaging through use of a negative lower bound in AB-OSEM reconstruction (i.e. by lifting the implicit non-negativity constraint of OSEM). When quantification tasks are considered, the overall error in the estimates (composed of both bias and standard deviation) is often of primary concern. An important finding of this work is that in most cases the activity concentration and the kinetic parameters obtained from images reconstructed using AB-OSEM showed a lower overall root mean squared error compared to the popular choices of either OSEM or FBP reconstruction for both cold and warm regions. As such, AB OSEM should be preferred instead of the standard OSEM and FBP reconstructions when kinetic parameter estimation is considered. Finally, this work shows example parametric images from the high-resolution research tomograph obtained using the different reconstruction methods. PMID- 21030749 TI - Feasibility study of multi-pass respiratory-gated helical tomotherapy of a moving target via binary MLC closure. AB - Gated radiotherapy of lung lesions is particularly complex for helical tomotherapy, due to the simultaneous motions of its three subsystems (gantry, couch and collimator). We propose a new way to implement gating for helical tomotherapy, namely multi-pass respiratory gating. In this method, gating is achieved by delivering only the beam projections that occur within a respiratory gating window, while blocking the rest of the beam projections by fully closing all collimator leaves. Due to the continuous couch motion, the planned beam projections must be delivered over multiple passes of radiation deliveries. After each pass, the patient couch is reset to its starting position, and the treatment recommences at a different phase of tumour motion to 'fill in' the previously blocked beam projections. The gating process may be repeated until the plan dose is delivered (full gating), or halted after a certain number of passes, with the entire remaining dose delivered in a final pass without gating (partial gating). The feasibility of the full gating approach was first tested for sinusoidal target motion, through experimental measurements with film and computer simulation. The optimal gating parameters for full and partial gating methods were then determined for various fractionation schemes through computer simulation, using a patient respiratory waveform. For sinusoidal motion, the PTV dose deviations of -29 to 5% observed without gating were reduced to range from 1 to 3% for a single fraction, with a 4 pass full gating. For a patient waveform, partial gating required fewer passes than full gating for all fractionation schemes. For a single fraction, the maximum allowed residual motion was only 4 mm, requiring large numbers of passes for both full (12) and partial (7 + 1) gating methods. The number of required passes decreased significantly for 3 and 30 fractions, allowing residual motion up to 7 mm. Overall, the multi-pass gating technique was shown to be a promising way to reduce the impact of lung tumour motion during helical tomotherapy. PMID- 21030750 TI - Improved scatter correction using adaptive scatter kernel superposition. AB - Accurate scatter correction is required to produce high-quality reconstructions of x-ray cone-beam computed tomography (CBCT) scans. This paper describes new scatter kernel superposition (SKS) algorithms for deconvolving scatter from projection data. The algorithms are designed to improve upon the conventional approach whose accuracy is limited by the use of symmetric kernels that characterize the scatter properties of uniform slabs. To model scatter transport in more realistic objects, nonstationary kernels, whose shapes adapt to local thickness variations in the projection data, are proposed. Two methods are introduced: (1) adaptive scatter kernel superposition (ASKS) requiring spatial domain convolutions and (2) fast adaptive scatter kernel superposition (fASKS) where, through a linearity approximation, convolution is efficiently performed in Fourier space. The conventional SKS algorithm, ASKS, and fASKS, were tested with Monte Carlo simulations and with phantom data acquired on a table-top CBCT system matching the Varian On-Board Imager (OBI). All three models accounted for scatter point-spread broadening due to object thickening, object edge effects, detector scatter properties and an anti-scatter grid. Hounsfield unit (HU) errors in reconstructions of a large pelvis phantom with a measured maximum scatter-to primary ratio over 200% were reduced from -90 +/- 58 HU (mean +/- standard deviation) with no scatter correction to 53 +/- 82 HU with SKS, to 19 +/- 25 HU with fASKS and to 13 +/- 21 HU with ASKS. HU accuracies and measured contrast were similarly improved in reconstructions of a body-sized elliptical Catphan phantom. The results show that the adaptive SKS methods offer significant advantages over the conventional scatter deconvolution technique. PMID- 21030751 TI - 3D conformal MRI-controlled transurethral ultrasound prostate therapy: validation of numerical simulations and demonstration in tissue-mimicking gel phantoms. AB - MRI-controlled transurethral ultrasound therapy uses a linear array of transducer elements and active temperature feedback to create volumes of thermal coagulation shaped to predefined prostate geometries in 3D. The specific aims of this work were to demonstrate the accuracy and repeatability of producing large volumes of thermal coagulation (>10 cc) that conform to 3D human prostate shapes in a tissue mimicking gel phantom, and to evaluate quantitatively the accuracy with which numerical simulations predict these 3D heating volumes under carefully controlled conditions. Eleven conformal 3D experiments were performed in a tissue-mimicking phantom within a 1.5T MR imager to obtain non-invasive temperature measurements during heating. Temperature feedback was used to control the rotation rate and ultrasound power of transurethral devices with up to five 3.5 * 5 mm active transducer elements. Heating patterns shaped to human prostate geometries were generated using devices operating at 4.7 or 8.0 MHz with surface acoustic intensities of up to 10 W cm(-2). Simulations were informed by transducer surface velocity measurements acquired with a scanning laser vibrometer enabling improved calculations of the acoustic pressure distribution in a gel phantom. Temperature dynamics were determined according to a FDTD solution to Pennes' BHTE. The 3D heating patterns produced in vitro were shaped very accurately to the prostate target volumes, within the spatial resolution of the MRI thermometry images. The volume of the treatment difference falling outside +/- 1 mm of the target boundary was, on average, 0.21 cc or 1.5% of the prostate volume. The numerical simulations predicted the extent and shape of the coagulation boundary produced in gel to within (mean +/- stdev [min, max]): 0.5 +/- 0.4 [-1.0, 2.1] and -0.05 +/- 0.4 [-1.2, 1.4] mm for the treatments at 4.7 and 8.0 MHz, respectively. The temperatures across all MRI thermometry images were predicted within -0.3 +/- 1.6 degrees C and 0.1 +/- 0.6 degrees C, inside and outside the prostate respectively, and the treatment time to within 6.8 min. The simulations also showed excellent agreement in regions of sharp temperature gradients near the transurethral and endorectal cooling devices. Conformal 3D volumes of thermal coagulation can be precisely matched to prostate shapes with transurethral ultrasound devices and active MRI temperature feedback. The accuracy of numerical simulations for MRI-controlled transurethral ultrasound prostate therapy was validated experimentally, reinforcing their utility as an effective treatment planning tool. PMID- 21030752 TI - Contrast enhancement of EPID images via difference imaging: a feasibility study. AB - In this study, the feasibility of difference imaging for improving the contrast of electronic portal imaging device (EPID) images is investigated. The difference imaging technique consists of the acquisition of two EPID images (with and without the placement of an additional layer of attenuating medium on the surface of the EPID) and the subtraction of one of these images from the other. The resulting difference image shows improved contrast, compared to a standard EPID image, since it is generated by lower-energy photons. Results of this study show that, firstly, this method can produce images exhibiting greater contrast than is seen in standard megavoltage EPID images and secondly, the optimal thickness of attenuating material for producing a maximum contrast enhancement may vary with phantom thickness and composition. Further studies of the possibilities and limitations of the difference imaging technique, and the physics behind it, are therefore recommended. PMID- 21030753 TI - Automatic Insall-Salvati ratio measurement on lateral knee x-ray images using model-guided landmark localization. AB - The Insall-Salvati ratio (ISR) is important for detecting two common clinical signs of knee disease: patella alta and patella baja. Furthermore, large inter operator differences in ISR measurement make an objective measurement system necessary for better clinical evaluation. In this paper, we define three specific bony landmarks for determining the ISR and then propose an x-ray image analysis system to localize these landmarks and measure the ISR. Due to inherent artifacts in x-ray images, such as unevenly distributed intensities, which make landmark localization difficult, we hence propose a registration-assisted active-shape model (RAASM) to localize these landmarks. We first construct a statistical model from a set of training images based on x-ray image intensity and patella shape. Since a knee x-ray image contains specific anatomical structures, we then design an algorithm, based on edge tracing, for patella feature extraction in order to automatically align the model to the patella image. We can estimate the landmark locations as well as the ISR after registration-assisted model fitting. Our proposed method successfully overcomes drawbacks caused by x-ray image artifacts. Experimental results show great agreement between the ISRs measured by the proposed method and by orthopedic clinicians. PMID- 21030754 TI - A practical vacuum sensor based on a ZnO nanowire array. AB - We report a practical vacuum pressure sensor based on a ZnO nanowire array (NWA). An oriented single-crystal ZnO NWA was synthesized by electrodeposition. The device consists of two ITO glass plates coated with a ZnO NWA. Scanning electron microscopy (SEM) and the x-ray diffraction (XRD) pattern show that the as-grown ZnO NWAs are single-crystal and roughly oriented with the ZnO(002) plane parallel to the substrate. Through measuring the pressure dependent resistance of the sensor at different gas species and temperatures, we discovered that the resistance increases monotonically with vacuum pressure. This demonstrates that a practical vacuum sensor could be fabricated since measurements were carried out with a normal multimeter, with no need for the high sensitivity and costly equipment as routinely required in nanotechnology for extremely weak signals. Measurement at elevated temperature (300 degrees C) showed that the vacuum sensor is much stabler and more sensitive to O(2) pressure. The principle of the device relates to the adsorbed oxygen species on the large surface area of a ZnO NWA to form a resistive depletion layer at the nanowire (NW) surface. PMID- 21030755 TI - Heterogeneous precipitation of silver nanoparticles on kaolinite plates. AB - Two different methods to obtain silver nanoparticles supported on kaolin crystals have been performed: the first one followed a thermal reduction and the second one a chemical reduction. In both cases, the silver nanoparticles with two different average particles size (ca.12 and 30 nm) were perfectly isolated and attached to the surface of the kaolin plates. The silver nanoparticles were localized mainly at the edge of the single crystal plates, the hydroxyl groups being the main centres of adsorption. The samples were fully characterized by XRD, UV-vis spectroscopy and TEM. The antimicrobial benefits of the composites were evaluated as antibacterial against common Gram-positive and Gram-negative bacteria, and antifungal activity against yeast. The results indicated a high antimicrobial activity for Escherichia coli JM 110 and Micrococcus luteus, while being inactive against yeast under our experimental conditions. The chemical analysis of Ag in the fermentation broths show that only a small portion of metal (<9 ppm) is released from the kaolin/metakaolin particles. Therefore, the risk of toxicity due to a high concentration of metal in the medium is minimized. PMID- 21030756 TI - Highly conformal SiO2/Al2O3 nanolaminate gas-diffusion barriers for large-area flexible electronics applications. AB - The present study demonstrates a flexible gas-diffusion barrier film, containing an SiO(2)/Al(2)O(3) nanolaminate on a plastic substrate. Highly uniform and conformal coatings can be made by alternating the exposure of a flexible polyethersulfone surface to vapors of SiO(2) and Al(2)O(3), at nanoscale thickness cycles via RF-magnetron sputtering deposition. The calcium degradation test indicates that 24 cycles of a 10/10 nm inorganic bilayer, top-coated by UV cured resin, greatly enhance the barrier performance, with a permeation rate of 3.79 * 10(-5) g m(-2) day(-1) based on the change in the ohmic behavior of the calcium sensor at 20 degrees C and 50% relative humidity. Also, the permeation rate for 30 cycles of an 8/8 nm inorganic bilayer coated with UV resin was beyond the limited measurable range of the Ca test at 60 degrees C and 95% relative humidity. It has been found that such laminate films can effectively suppress the void defects of a single inorganic layer, and are significantly less sensitive against moisture permeation. This nanostructure, fabricated by an RF-sputtering process at room temperature, is verified as being useful for highly water sensitive organic electronics fabricated on plastic substrates. PMID- 21030757 TI - Octreotide-modification enhances the delivery and targeting of doxorubicin-loaded liposomes to somatostatin receptors expressing tumor in vitro and in vivo. AB - Octreotide is believed to be the ligand of somatostatin receptors (SSTRs) which are widely used in tumor diagnosis and clinical therapy. In the present work, a new targeting conjugate, octreotide-polyethylene glycol-phosphatidylethanolamine (Oct-PEG-PE), was developed for the assembling of liposome, and the effect of octreotide-modification on the enhancement of the delivery and targeting of doxorubicin-loaded liposomes was investigated in vitro and in vivo. Oct-PEG-PE was synthesized by a three-step reaction involving two derivative intermediate formations of bis (p-nitrophenyl carbonate)-PEG ((pNP)(2)-PEG) and pNP-PEG-PE. The Oct-modified and unmodified liposomes (DOX-OL and DOX-CL) were prepared by the ammonium sulfate gradient method. Both drug uptake assay and cell apoptosis assay suggested that DOX-OL noticeably increased the uptake of DOX in SMMC-7721 cells and showed a more significant cytotoxicity, compared with DOX-CL. The effect of DOX-OL was remarkably inhibited by free octreotide. In contrast, no significant difference in drug cytotoxicity was found between DOX-OL and DOX-CL in CHO cells without obvious expression of SSTRs. The study of ex vivo fluorescence tissues imaging of BALB/c mice and in vivo tissue distribution of B16 tumor-bearing mice indicated that DOX-OL caused remarkable accumulation of DOX in melanoma tumors and the pancreas, in which the SSTRs are highly expressed. PMID- 21030758 TI - Highly efficient luminescence from hybrid structures of ZnO/multi-walled carbon nanotubes for high performance display applications. AB - We report an interesting observation on strong enhancement in green luminescence from hybrid ZnO/multi-walled carbon nanotubes (MWCNTs). The hybrid structures were synthesized via a high temperature sintering method. The strong green emission at 510 nm has been attributed to surface defects of ZnO, originating from interactions between ZnO and the MWCNT surface, which has been confirmed by high resolution transmission electron microscopy and x-ray photoelectron spectroscopy. Furthermore, the two-dimensional (2D) layer of this hybrid material shows a high degree of homogeneity and 82% transparency. Time resolved emission spectroscopy measurement shows a photoluminescence decay time in microseconds, which is suitable for making optoelectronic devices. PMID- 21030760 TI - Proton-based total-dose irradiation effects on Cu/HfO2:Cu/Pt ReRAM devices. AB - The resistive switching properties of Cu-doped-HfO(2)-based resistive-random access-memory (ReRAM) devices are investigated under proton-based irradiations with different high-range total doses of 1.5, 3 and 5 Giga-rad[Si]. The measurement results obtained immediately after irradiation demonstrate that the proton-based total dose will introduce significant variations in the operation voltages and resistance values. These effects are enhanced almost linearly when the dose increases from 1.5 to 5 Giga-rad[Si]. Furthermore, five days after irradiation, the electrical properties of the device rebound, resulting in reduced operation voltages and resistance values. This is consistent with the time-dependent super-recovery behavior observed previously in CMOS gate oxide. These results can be explained by the proton irradiation effect on the electron/hole trap density inside HfO(2) and its impact on ReRAM device metallic filament formation-and-rupture, which is based on electrolyte theory. PMID- 21030759 TI - Tumor cell apoptosis induced by nanoparticle conjugate in combination with radiation therapy. AB - Semiconductor nanoparticles conjugated to photosensitizers have been shown to increase tumor cell death with ionizing radiation but the mechanism, particularly the role of photodynamic therapy in the process, was unknown. We used a molecular probe to measure production of (1)O(2) to quantify the component of photodynamic cell-killing in an in vitro system. The intracellular distribution of the nanoparticle conjugate (NC) was determined by the co-localization of nanoparticles and the lysotracker. Induction of apoptosis was measured by the TUNEL assay and western blot analysis of the cleaved caspase-3. As a result, dose dependent (1)O(2) production was observed with 48 nm NC after irradiating with 6 MV x-rays. A high geometrical coincidence between the fluorescence emission of the nanoparticle and lysotracker was observed using confocal microscopy. Finally, apoptosis, as indicated by the TUNEL stain and cleavage of the caspase-3, was observed in cells treated by both the NC and 6 Gy of radiation but not in cells treated with radiation alone. In conclusion, the cell death induced by the NC in combination with radiation is consistent with a supra-additive effect to radiation-or NC-alone-killing and is mediated by an NC-induced photodynamic therapy mechanism, which is distinctly different from that for radiation-killing alone. By providing a second distinct cell-killing mechanism, this nanoparticle conjugate has great promise as a targeted physical radiosensitizer aimed at overcoming radioresistant tumor clonogens or/and reducing normal tissue toxicity by using a lower ionizing radiation dose. PMID- 21030762 TI - Thermal conductivity of carbon nanotube cross-bar structures. AB - We use non-equilibrium molecular dynamics (NEMD) to compute the thermal conductivity (kappa) of orthogonally ordered cross-bar structures of single walled carbon nanotubes. Such structures exhibit extremely low thermal conductivity in the range of 0.02-0.07 W m(-1) K(-1). These values are five orders of magnitude smaller than the axial thermal conductivity of individual carbon nanotubes, and are comparable to the thermal conductivity of still air. PMID- 21030761 TI - Substrate-facilitated nanoparticle sintering and component interconnection procedure. AB - Room temperature substrate-facilitated sintering of nanoparticles is demonstrated using commercially available silver nanoparticle ink and inkjet printing substrates. The sintering mechanism is based on the chemical removal of the nanoparticle stabilizing ligand and is shown to provide conductivity above one fourth that of bulk silver. A novel approach to attach discrete components to printed conductors is presented, where the sintered silver provides the metallic interconnects with good electrical and mechanical properties. A process for printing and chip-on-demand assembly is suggested. PMID- 21030763 TI - Fluorescence studies of Rhodamine 6G functionalized silicon oxide nanostructures. AB - Selective anchoring of optically active molecules on nanostructured surfaces is a promising step towards the creation of nanoscale devices with new functionalities. Recently we have demonstrated the electrostatic attachment of charged fluorescent molecules on silicon oxide nanostructures prepared by atomic force microscopy (AFM) nanolithography via local anodic oxidation (LAO) of dodecyl-terminated silicon. In this paper we report on our findings from a more detailed optical investigation of the bound dye Rhodamine 6G. High sensitivity optical wide field microscopy as well as confocal laser microscopy have been used to characterize the Rhodamine fluorescence emission. A highly interesting question concerns the interaction between an emitter close to a silicon surface because mechanisms such as energy transfer and fluorescence quenching will occur which are still not fully understood. Since the oxide thickness can be varied during preparation continuously from 1 to ~ 5 nm, it is possible to investigate the fluorescence of the bound dye in close proximity to the underlying silicon. Using confocal laser microscopy we were also able to obtain optical spectra from the bound molecules. Together with the results from an analysis of their photochemical bleaching behaviour, we conjecture that some of the Rhodamine 6G molecules on the structure are interacting with the oxide, causing a spectral shift and differences in their photochemical properties. PMID- 21030764 TI - Shape-controlled nanopores in single crystals. AB - Nanometer length-scale holes (nanopores) are often formed in amorphous materials for fundamental studies of molecular mass transport. In the current study, electron beam irradiation in the transmission electron microscope was used to form nanopores in a crystalline material (Si). Analysis of the nanopores showed that they are formed by knock-on of atoms by the high energy incident electron beam, and surface diffusion is partially responsible for the hour-glass shapes that are found for some nanopores. Energetically favorable three-dimensional shapes of nanopores were simulated, and the nanopores simulated in the model crystalline material were found to be more stable than the nanopores simulated in the amorphous material. The nanopore shape was also found to depend on the nanopore diameter-to-length ratio. Based on the above, we demonstrate the advantage in using a crystalline material for nanopore formation and show that control of the three-dimensional shape of nanopores formed by electron beam irradiation is possible. PMID- 21030765 TI - Effects of electron-transfer chemical modification on the electrical characteristics of graphene. AB - Because of the large reactivity of single layer graphene to electron-transfer chemistries, 4-nitrobenzene diazonium tetrafluoroborate is employed to modify the electrical properties of graphene field-effect transistors. After modification, the transfer characteristics of chemically modified graphene show a reduction in the minimum conductivity, electron-hole mobility asymmetry, a decrease in the electron/hole mobility, and a positive shift of the charge neutrality point with broadening of the minimum conductivity region. These phenomena are attributed to a dediazoniation reaction and the adsorbates on the graphene surface. PMID- 21030766 TI - Microcalorimetric, spectroscopic and microscopic investigation on the toxic effects of CdTe quantum dots on Halobacterium halobium R1. AB - The biological effect of CdTe quantum dots (QDs) on Halobacterium halobium R1 (H. halobium R1) growth was analyzed by a microcalorimetric technique. By using a TAM air eight channels microcalorimeter, the thermogenic curves of H. halobium R1 growth were obtained at 37 degrees C. To analyze the results, the maximum heat power (P(m)) and the growth rate constants (k) were determined, which showed that they were correlated to the concentration of QDs. The addition of quantum dots caused a gradual increase of P(m) and k at low concentrations of QDs, and a conspicuous decrease at high concentrations. For confirmation, the turbidity (OD(600)) and respiratory rate at different concentrations of QDs were studied. The morphology of H. halobium R1 cells both in the absence and presence of QDs was examined by transmission electron microscopy (TEM). The results of these studies were corroborated with ones derived from microcalorimetry. In this work, the mechanism of cytotoxicity of QDs was explored through fluorescence spectroscopy, inductively coupled plasma mass spectrometry (ICP-MS) and microcalorimetry. It was clear that metabolic mechanism of H. halobium R1 growth was changed by the addition of QDs. To the best of our knowledge, the thermokinetics and toxicology of CdTe QDs against H. halobium R1 were obtained for the first time by microcalorimetry. PMID- 21030767 TI - Control of the crystal structure of InAs nanowires by tuning contributions of adatom diffusion. AB - The dependence of crystal structure on contributions of adatom diffusion (ADD) and precursor direct impingement (DIM) was investigated for vapor-liquid-solid growth of InAs nanowires (NWs). The ADD contributions from the sidewalls and substrate surface can be changed by using GaAs NWs of different length as the basis for growing InAs NWs. We found that pure zinc-blende structure is favored when DIM contributions dominate. Moreover, without changing the NW diameter or growth parameters (such as temperature or V/III ratio), a transition from zinc blende to wurtzite structure can be realized by increasing the ADD contributions. A nucleation model is proposed in which ADD and DIM contributions play different roles in determining the location and phase of the nucleus. PMID- 21030768 TI - Thermal activation and quantum field emission in a sketch-based oxide nanotransistor. AB - We report direct measurements of the potential barriers and electronic coupling between nanowire segments within a sketch-based oxide nanotransistor (SketchFET) device. Near room temperature, switching is governed by thermal activation across a potential barrier controlled by the nanowire gate. Below T = 150 K, current flow is dominated by quantum field emission. Sharp maxima in the quantum field emission, observed at T(C1) = 65 K and T(C2) = 25 K, arise from dielectric anomalies occurring at structural phase transitions in the SrTiO(3) layer. This direct measurement of the source-drain and gate-drain energy barriers is crucial for the development of room-temperature logic and memory elements and low temperature quantum devices. PMID- 21030769 TI - Investigation of initial growth of ZnO nanowires and their growth mechanism. AB - ZnO nanowires were synthesized on Si substrates by a simple metal vapor deposition method without any catalysts. The initial growth and the growth mechanism of the ZnO nanowires were studied using scanning and transmission electron microscopy. We found that the ZnO nanowires grew on the Si substrate via a self-seeding vapor-solid mechanism. The growth process of the ZnO nanowires consisted of four steps: self-seeding, one-dimensional epitaxial growth of the nanowires on the seeds by a base-growth mode, further acceleration of nanowire growth with additional seeding, and active formation of the nanowires. PMID- 21030770 TI - SiC/C nanocomposites with inverse opal structure. AB - The synthesis, morphology, structural and optical characteristics of SiC/C nanocomposites with an inverse opal lattice have been investigated. The samples were prepared by thermochemical treatment of opal matrices filled with carbon compounds which was followed by silicon dioxide dissolution. The samples were studied by electron microscopy, x-ray diffraction, photoluminescence, IR and Raman scattering spectroscopy. The electron microscopy data revealed a highly porous periodic structure which was a three-dimensional replica of the voids of the initial opal lattice. The hexagonal silicon carbide was found to be non uniformly distributed throughout the volume, its greater part located in the surface layer up to 50 um deep. The data of x-ray diffraction, IR and Raman scattering spectroscopy enabled us to assume that the composite had hexagonal diamond fragments. The photoluminescence and optical reflection spectra of the composites have been measured. PMID- 21030771 TI - Large flexibility of high aspect ratio carbon nanostructures fabricated by electron-beam-induced deposition. AB - The mechanical properties of free-standing electron beam deposited amorphous carbon structures have been studied using atomic force microscopy. The fabricated carbon blades are found to be extraordinarily flexible, capable of undergoing vertical deflection up to ~ 75% of their total length without inelastic deformation. The elastic bending modulus of these structures was calculated to be 28 +/- 10 GPa. PMID- 21030772 TI - A synthesis and sensing application of hollow ZnO nanofibers with uniform wall thicknesses grown using polymer templates. AB - A novel approach is applied to fabricating hollow ZnO nanofibers (ZNFs) with uniform wall thicknesses. In this approach, polymers synthesized by electrospinning are used as sacrificial templates and ZnO is subsequently deposited on these templates using atomic layer deposition, which makes ZnO uniformly cover the round surface of the polymer nanofibers. Heat treatments result in the selective removal of the polymer templates and the formation of hollow ZNFs with very uniform wall thicknesses. To test a potential use of hollow ZNFs in chemical gas sensors, their sensing properties with regard to O(2), NO(2), and CO are investigated in a comparative manner with those of normal ZnO nanofibers. The excellent sensing properties observed in the hollow ZNF sensor are ascribed to (1) the more pronounced change in resistance due to the presence of nanograins and (2) the doubling of the surface-to-volume ratio due to the generation of inner surfaces. PMID- 21030773 TI - Vertically aligned ZnO/amorphous-Si core-shell heterostructured nanowire arrays. AB - We report the synthesis of vertically aligned ZnO/a-Si core-shell nanowire arrays (ZnO nanowires coated with amorphous silicon) through chemical vapor deposition. The core-shell heterostructured nanowires possessed uniform morphology and the thickness of the amorphous silicon shells could be controlled easily by tuning the deposition duration and temperature. The core-shell heterostructured nanowires exhibited enhanced antireflection and absorption performance as well as tunable PL properties. Because the individual ZnO/a-Si nanowires showed p-type characteristics and the ZnO cores were n-type semiconductors, the core-shell nanowires formed p-n junctions naturally. PMID- 21030774 TI - Near-infrared quantum-dot-based non-invasive in vivo imaging of squamous cell carcinoma U14. AB - Near-infrared (near-ir) quantum dots (QDs) are well known for their excellent optical characteristics. They hold great potential for applications in non invasive long term observation and tracing of cells in vivo. Here, near-ir QDs with an emission wavelength of 800 nm (QD800) were used to label squamous cell carcinoma cell line U14 (U14/QD800). The effect of tissue depth and animal fur on the imaging sensitivity and stability was evaluated following subcutaneous and intramuscular injection into Kunming mice, employing an in vivo imaging system. We have demonstrated that QD800-based visual in vivo imaging increased the sensitivity of cancer early detection by a factor of 100 compared with traditional detection methods. More importantly, this study proved for the first time that animal fur has a serious impact on the detection sensitivity and duration of QD-based in vivo imaging. In general, the duration and sensitivity of QD800 for in vivo imaging were not greatly affected by a depth less than 1.8 +/- 0.21 mm (subcutaneous or intramuscular). This study provides critical reference data for further research on near-ir QD-based early detection and in vivo visual observation of cancer. PMID- 21030775 TI - Ge-rich islands grown on patterned Si substrates by low-energy plasma-enhanced chemical vapour deposition. AB - Si(1-x)Ge(x) islands grown on Si patterned substrates have received considerable attention during the last decade for potential applications in microelectronics and optoelectronics. In this work we propose a new methodology to grow Ge-rich islands using a chemical vapour deposition technique. Electron-beam lithography is used to pre-pattern Si substrates, creating material traps. Epitaxial deposition of thin Ge films by low-energy plasma-enhanced chemical vapour deposition then leads to the formation of Ge-rich Si(1-x)Ge(x) islands (x > 0.8) with a homogeneous size distribution, precisely positioned with respect to the substrate pattern. The island morphology was characterized by atomic force microscopy, and the Ge content and strain in the islands was studied by MURaman spectroscopy. This characterization indicates a uniform distribution of islands with high Ge content and low strain: this suggests that the relatively high growth rate (0.1 nm s(-1)) and low temperature (650 degrees C) used is able to limit Si intermixing, while maintaining a long enough adatom diffusion length to prevent nucleation of islands outside pits. This offers the novel possibility of using these Ge-rich islands to induce strain in a Si cap. PMID- 21030776 TI - Logic circuits based on individual semiconducting and metallic carbon-nanotube devices. AB - Nanoscale transistors employing an individual semiconducting carbon nanotube as the channel hold great potential for logic circuits with large integration densities that can be manufactured on glass or plastic substrates. Carbon nanotubes are usually produced as a mixture of semiconducting and metallic nanotubes. Since only semiconducting nanotubes yield transistors, the metallic nanotubes are typically not utilized. However, integrated circuits often require not only transistors, but also resistive load devices. Here we show that many of the metallic carbon nanotubes that are deposited on the substrate along with the semiconducting nanotubes can be conveniently utilized as load resistors with favorable characteristics for the design of integrated circuits. We also demonstrate the fabrication of arrays of transistors and resistors, each based on an individual semiconducting or metallic carbon nanotube, and their integration on glass substrates into logic circuits with switching frequencies of up to 500 kHz using a custom-designed metal interconnect layer. PMID- 21030777 TI - Resistive switching via the converse magnetoelectric effect in ferromagnetic multilayers on ferroelectric substrates. AB - A voltage-controlled resistive switching is predicted for ferromagnetic multilayers and spin valves mechanically coupled to a ferroelectric substrate. The switching between low- and high-resistance states results from the strain driven magnetization reorientations by about 90 degrees , which are shown to occur in ferromagnetic layers with a high magnetostriction and weak cubic magnetocrystalline anisotropy. Such reorientations, not requiring external magnetic fields, can be realized experimentally by applying moderate electric field to a thick substrate (bulk or membrane type) made of a relaxor ferroelectric having ultrahigh piezoelectric coefficients. The proposed multiferroic hybrids exhibiting giant magnetoresistance may be employed as electric-write nonvolatile magnetic memory cells with nondestructive readout. PMID- 21030778 TI - SERS detection of biomolecules using lithographed nanoparticles towards a reproducible SERS biosensor. AB - In this paper we highlight the accurate spectral detection of bovine serum albumin and ribonuclease-A using a surface-enhanced Raman scattering (SERS) substrate based on gold nanocylinders obtained by electron-beam lithography (EBL). The nanocylinders have diameters from 100 to 180 nm with a gap of 200 nm. We demonstrate that optimizing the size and the shape of the lithographed gold nanocylinders, we can obtain SERS spectra of proteins at low concentration. This SERS study enabled us to estimate high enhancement factors (10(5) for BSA and 10(7) for RNase-A) of important bands in the protein Raman spectrum measured for 1 mM concentration. We demonstrate that, to reach the highest enhancement, it is necessary to optimize the SERS signal and that the main parameter of optimization is the LSPR position. The LSPR have to be suitably located between the laser excitation wavelength, which is 632.8 nm, and the position of the considered Raman band. Our study underlines the efficiency of gold nanocylinder arrays in the spectral detection of proteins. PMID- 21030782 TI - ENU-based gene-driven mutagenesis in the mouse: a next-generation gene-targeting system. AB - As a new mouse mutant resource, the RIKEN ENU-based gene-driven mutagenesis system in the mouse has been available to the research community since 2002. By using random base-substitution mutagenesis with ENU, a new reverse genetics infrastructure has been developed as a next-generation gene-targeting system. The construction of a large-scale mutant mouse library and high-throughput mutation discovery systems were the keys making it practically feasible. The RIKEN mutant mouse library consists of ~ 10,000 G1 mice, within which 100-150 mutant strains have been established based on users' requests every year. Use of the system is very simple: users 1) download an application form from our web site and send to us, and 2) design the PCR primers for the target gene. Then, we screen the RIKEN mutant mouse library and report all the detected mutations to the user. From among the allelic series of discovered mutations, users decide which mutant strain(s) to analyze and request the live mutant strain for functional studies of the target gene. Users have been reporting various functional mutations in the RIKEN mutant mouse library: e.g., missense, knockout-type and even functional non coding mutations. In the near future, next-generation re-sequencing systems should drastically enhance the utility of the ENU-based gene-driven mutagenesis not only for the mouse but also for other species. PMID- 21030783 TI - Expanding members and roles of the calpain superfamily and their genetically modified animals. AB - Calpains are intracellular Ca2(+)-dependent cysteine proteases (Clan CA, family C02, EC 3.4.22.17) found in almost all eukaryotes and some bacteria. Calpains display limited proteolytic activity at neutral pH, proteolysing substrates to transform and modulate their structures and activities, and are therefore called "modulator proteases". The human genome has 15 genes that encode a calpain-like protease domain, generating diverse calpain homologues that possess combinations of several functional domains such as Ca2(+)-binding domains and Zn-finger domains. The importance of the physiological roles of calpains is reflected in the fact that particular defects in calpain functionality cause a variety of deficiencies in many different organisms, including lethality, muscular dystrophies, lissencephaly, and tumorigenesis. In this review, the unique characteristics of this distinctive protease superfamily are introduced in terms of genetically modified animals, some of which are animal models of calpain deficiency diseases. PMID- 21030784 TI - Mitochondrial DNA diversity among three subpopulations of cynomolgus macaques (Macaca fascicularis) originating from the Indochinese region. AB - The cynomolgus macaque (Macaca fascicularis) has emerged as an important experimental animal model for biomedical research in various domains, necessitating the more extensive characterization of the genetic backgrounds influencing the macaque's response to drugs and sensitivity to experimental disease. The diversity of the variable mitochondrial DNA (mtDNA) D-loop region has been analyzed phylogenetically among geographically isolated populations or within subdivisions of the same regional population. However, the genetic differences among several substructures originating from a common population have not yet been investigated. By sequencing fragments of the mtDNA D-loop region from two subpopulations from the Indochinese region (Cambodian-Chinese and Vietnamese) along with two native Indonesian and Filipino populations, we identified 87 mtDNA D-loop haplotypes, of which 67 are new. The phylogenetic relationship suggests that the Indochinese haplotypes are intermingled in comparison to the distinct divergence of the Indonesian and Filipino lineages. The subpopulations were shown by estimation of evolutionary divergence and Wright's F-statistic (Fst) to have little genetic differentiation. Altogether, the subpopulations may be used in biomedical research, even though a slight difference is observed in haplotype frequencies among them. Therefore, genetic diversity analyses will be necessary for the elucidation of genetic differences among the populations, as well as to obtain a better understanding of genetic diversity for biomedical research. This will involve the selection of macaques and the monitoring of genetic heterogeneity among and within breeding facilities. PMID- 21030785 TI - Augmented induction of antigen-specific cytotoxic T cell responses against canine hepatitis by co-immunization with pVAX1-CpG-Loop and adjuvants in BALB/c mice. AB - The objective of this study was to obtain better antigen specific cytotoxic T cell responses in vivo. We examined the augmented induction of antigen-specific cytotoxic T cell responses to co-administration of oligonucleotides (CpG-ODN), dimethyl dioctadecyl ammonium bromide (DDA), and LipofectamineTM 2000 with a DNA vaccine (pVAX1-CpG-Loop) and boosting with pVAX1-CpG-Loop in BALB/c mice. The results show that Loop protein-specific T cell proliferation, cytotoxic T cell activity, and the production of CD8+ T cells and IFN-gamma were enhanced after co immunization of mice with adjuvants and pVAX1-CpG-Loop. We demonstrated that significant T cell-mediated immune responses were induced in the mice with the help of DDA, CpG-ODN and LipofectamineTM 2000. PMID- 21030786 TI - The effects of interleukin-6 and cytokine-induced neutrophil chemoattractant-1 on alpha2-macroglobulin production in rats. AB - We investigated the effects of interleukin-6 (IL-6) and cytokine-induced neutrophil chemoattractant-1 (CINC-1) on alpha(2)-macroglobulin (alpha2M) production in rats. IL-6-rich and CINC-1-rich fractions were separated from serum obtained from rats 12 h after injection with turpentine oil using gel chromatography. Sexual dimorphism was observed in the peak levels of alpha2M after injection of IL-6-, CINC-1-, or a mixture of IL-6-and-CINC-1-rich fractions. No significant differences in alpha2M levels were observed in males after injection with IL-6- or CINC-1-rich fractions and those injected with normal serum obtained from healthy rats (control). In contrast, serum levels of alpha2M, 6 to 120 h after injection of a mixture of IL-6- and CINC-1-rich fractions were significantly higher than in control rats. These results suggest that IL-6 and CINC-1 contribute to alpha2M production in rats only when IL-6 and CINC-1 act synergistically. PMID- 21030787 TI - Inducible nitric oxide distribution in the fatty liver of a mouse with high fat diet-induced obesity. AB - Obesity is a condition of abnormal adipose tissue storage and recently it has been recognized as a major factor in metabolic syndrome. High-fat diet-induced obesity in the C57BL/6 mouse is an important animal model because of its similarities with human obesity. The aim of the present study was to estimate obesity, liver injury and steatohepatitis, and the distribution of inducible nitric oxide synthase (iNOS) in mice with high-fat diet induced obesity. Three week-old male C57BL/6J mice were fed either a high-fat diet (D-60: 60 kcal% fat, or D-45: 45 kcal% fat) or a normal diet (D-10: 10 kcal% fat) for 15 weeks. Oral glucose tolerance tests and intraperitoneal glucose tolerance tests showed that the D-60 mice had severely impaired glucose tolerance. In serum chemistry values and histopathological lesions, the D-60 group showed severe steatohepatitis. A distinct positive signal for iNOS was detected by immunohistochemistry in the cytoplasm of hepatocytes around the central vein in the D-45 and D-60 groups. Serum insulin levels and insulin immunohistochemistry in the pancreas showed pancreatic injury and insulin resistance in the D-60 group. We observed the presence of more iNOS in the high-fat diet-induced obese mouse, which has characteristics of non-alcoholic steatohepatitis (NASH) and diabetes, and expect that these background pathological data will be useful in research on obesity, diabetes mellitus, and non-alcoholic fatty liver disease. PMID- 21030788 TI - Ovarian expression of inhibin-subunits, 3beta-hydroxysteroid dehydrogenase, and cytochrome P450 aromatase during the estrous cycle and pregnancy of shiba goats (Capra hircus). AB - The cellular localization of the inhibin subunits (alpha, beta(A), and beta (B)), steroidogenic enzymes (3beta-hydroxysteroid dehydrogenase (3betaHSD) and cytochrome P450 aromatase (P450arom) were evaluated in the ovaries of cyclic (n=6) and pregnant (n=2) Shiba goats (Capra Hircus). The immunointensity of inhibin alpha and beta(A) subunits showed an increase in the granulosa cells (GC) of developing follicles. Inhibin beta(B) subunit and P450arom showed high expression in GC of antral follicles. 3betaHSD immunoreactivity was uniform in preantral and antral follicles. In follicular phase and late pregnancy, there was a strong expression of inhibin alpha subunit in GC of antral follicles. Although in mid pregnancy, antral follicles GC showed moderate immunostaining of inhibin beta subunits, the immunoreactivity of inhibin beta(A) and beta(B) subunits was high during the follicular and luteal stages, respectively. While, immunoreactivity of GC to P450arom was moderate during all studied stages, and 3betaHSD immunoreactivity was plentiful in antral follicles during the luteal phase. The immunoreactivity to inhibin alpha subunit and P450arom was abundant during mid pregnancy in the luteal tissues. Immunoreaction to inhibin beta subunits was faint-to-moderate in cyclic and pregnancy corpora lutea. Immunoexpression of 3betaHSD was maximal in late pregnancy corpora lutea. The present results suggest that, in goats, the GC of antral follicles are the main source of dimeric inhibins and that corpora lutea may partially participate in the secretion of inhibin. Changes in ovarian hormonal levels might depend on the synthesizing capacity of hormones in the follicles and corpora lutea to regulate the goat's reproductive stages. PMID- 21030789 TI - Flk1-GFP BAC Tg mice: an animal model for the study of blood vessel development. AB - The mouse Flk1 (also called Kdr or Vegf-r2) gene encodes a receptor for VEGF-A. Flk1 is expressed in endothelial cells of the developing embryo. Recent studies have shown that Flk1 is expressed by multi-potent mesodermal progenitors, which give rise to various hematopoietic and cardiovascular cell lineages during development, and in differentiating ES cells, which may be used for cell transplantation therapy to treat cardiovascular diseases. Given its developmental and clinical importance in cardiovascular tissues, an animal model of Flk1 activity would be very useful. Here, we report the generation of Flk1-GFP BAC transgenic mice for monitoring Flk1 gene expression during development. We show that GFP expression in these mice serves as a surrogate marker for developing endothelial cells. Immunohistochemical analysis showed that the regions of expression of GFP and endogenous FLK1 largely overlap. Uniform GFP expression was observed in most endothelial cells at 8.5 dpc and thereafter. Flk1-GFP BAC transgenic mice should be useful for the study of both vascular development and pathological angiogenesis. PMID- 21030790 TI - The influence of dietary restriction on the development of diabetes and pancreatitis in female WBN/Kob-fatty rats. AB - Original WBN/Kob male rats commonly develop chronic pancreatitis by the age of 3 months, while diabetes mellitus occurs at 9 months. In contrast, female rats of this strain do not show pancreatitis or diabetes. The WBN/Kob-fatty rat is a homozygous (fa/fa) congenic strain for the fa allele of the leptin receptor gene (Lepr). In WBN/Kob-fatty rats, both females and males provide a model of non insulin-dependent diabetes with obesity. The leptin receptor fatty gene (Lepr(fa)) induces obesity and hyperphagia. In the present study, we examined the effect of dietary restriction on pancreatitis and diabetes in female WBN/Kob fatty rats. Five female fatty rats comprised a restricted feeding group with paired-feeding from 3 to 13 weeks of age, and five female lean rats comprised a control group with paired-feeding. At 13 weeks of age, two of the five female fatty rats of the control group developed diabetes mellitus, while no female fatty rats of the restricted feeding group developed diabetes mellitus. At this stage, pathological changes of the pancreas were observed in female fatty rats. All female fatty rats showed severe interlobular, intra-lobular and intra-islet fibrosis. In female fatty rats of the restricted feeding group, pathological changes of the pancreas were milder those of the free-feeding fatty group. Although dietary restriction could not completely prevent pancreatitis in female fatty rats, the development of diabetes was inhibited by its reduction of the severity of pancreatitis. PMID- 21030791 TI - Maternal exposure to isobutyl-paraben impairs social recognition in adult female rats. AB - Isobutyl-paraben (IBP), a widely used preservative, exhibits estrogenic activity. We analyzed the effects of exposure to IBP during gestation and lactation via dam on social recognition behavior in ovariectomized offspring of Sprague-Dawley rats. Offspring were ovariectomized at 7 weeks of age, and were used in a social recognition test at 16 weeks of age. Each offspring was exposed to a novel ovariectomized rat four times and to a second novel rat in a fifth exposure. We counted the investigations by offspring of intruder rats. The IBP-exposed rats showed impaired social behavior compared with controls. These data imply that early exposure to IBP may have an effect on adult social behavior, which is reported to be an autism spectrum disorders in humans. PMID- 21030792 TI - Effects of animal care procedures on plasma corticosterone levels in group-housed mice during the nocturnal active phase. AB - C57BL/6 mice were housed five per cage on a 12:12 h light/dark cycle. All animal care, including bed cleaning, was carried out during the nonactive phase. After 2 weeks, mean plasma corticosterone levels, collected during the nonactive (ZT6) and active (ZT18) phases, were 66.0 and 270.9 ng/ml, respectively. The values at ZT18 gradually increased in the order of the mice used for blood collection, but not at ZT6. When animal care was carried out at ZT18, the increasing pattern of plasma corticosterone levels previously observed at ZT18 was less pronounced after 2 weeks of acclimatization, and was not observed after 4 weeks. Therefore, animal care should be carried out in the active phase for at least 4 weeks before experiments involving stress responses in the active phase. PMID- 21030793 TI - Molecular cloning and expression of canine prolactin gene. AB - We isolated canine prolactin cDNA from a dog pituitary cDNA library. The 930-bp nucleotide sequence covered the entire open reading frame encoding the putative 229 amino acids. It was located in chromosome 35, and had five exons. The amino acid sequence was highly homologous to the feline and porcine sequences. To generate recombinant canine prolactin, plasmids for full-length canine prolactin were constructed and transfected into the mammalian HEK293 cell line. The recombinant prolactin was secreted into the medium as an N-linked glycosylated (31 kDa) or non-glycosylated (27 kDa) protein. Western blotting revealed both of these bands were canine pituitary protein extracts. PMID- 21030794 TI - Increased risk of hospitalization related to motor vehicle accidents among people taking zolpidem: a case-crossover study. AB - BACKGROUND: Several epidemiological and experimental studies have found a positive association between the risk of motor vehicle accidents (MVAs) and use of zopiclone and benzodiazepines. There is, however, little evidence of any risk of MVA attributable to the use of zolpidem 1 day before such accidents. We attempted to determine whether the use of zolpidem 1 day before is associated with an increased risk of an MVA. METHODS: Using a 1-million-person randomly sampled cohort from the Taiwan National Health Insurance reimbursement database, 12 929 subjects were identified as having been hospitalized between 1998 and 2004 due to an MVA. Using a case-crossover design, we selected the day before an MVA as the case period for each subject, and the 91st, 182nd, and 273rd days before the case period as 3 retrospective control periods. Conditional logistical regression models were constructed to calculate the odds ratio (OR) of having an MVA and the exposure of zolpidem 1 day before. We calculated doses of benzodiazepines, zopiclone, and zolpidem based on their defined daily dose. RESULTS: The adjusted OR for involvement in an MVA after taking 1 defined daily dose of zolpidem was 1.74 (95% confidence interval: 1.25-2.43). There were also positive effects for different washout periods and cumulative doses at 7, 14, 21, and 28 days before the occurrence of an MVA. CONCLUSIONS: Use of zolpidem 1 day before might be associated with an increased risk of MVA. Thus, precautionary warnings should be provided when prescribing zolpidem. PMID- 21030795 TI - Acute adverse effects of radiation therapy on HIV-positive patients in Japan: study of 31 cases at Tokyo Metropolitan Komagome Hospital. AB - Recently, the number of human immunodeficiency virus (HIV) -positive patients has increased in Japan. HIV-positive patients are at a higher risk of cancer than the general population. This paper retrospectively reports the acute adverse effects of radiation therapy on HIV-positive patients who were treated at Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital (TMCICK). Thirty-one cases involving 24 HIV-positive cancer patients who were treated at TMCICK from January 1997 to March 2009 were included in this study. All acute adverse effects of radiation therapy were examined during, and one month after, the last radiation therapy session. Acute adverse effects were classified according to the site of radiation therapy treatment and analyzed using the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Grade 3 acute adverse effects were seen in 17% of cases, and Grade 2 toxicities were found in 23% of patients. Damage to the skin and mucosa, including stomatitis or diarrhea, tended to occur after low-dose radiation therapy; however, no severe acute adverse effects were seen in other organs, such as the brain, lung, and bone. Acute adverse effects tended to occur earlier in HIV-positive patients and became severe more frequently than in the general population. In particular, disorders of the mucosa, such as those of the oral cavity, pharynx, and intestine, tended to occur rapidly. It was shown that radiation therapy is safe when treatment is performed carefully and that it is a very useful treatment for cancer in HIV positive patients. PMID- 21030796 TI - Investigation on effect of image lag in fluoroscopic images obtained with a dynamic flat-panel detector (FPD) on accuracy of target tracking in radiotherapy. AB - Real-time tumor tracking in external radiotherapy can be achieved by diagnostic (kV) X-ray imaging with a dynamic flat-panel detector (FPD). The purpose of this study was to address image lag in target tracking and its influence on the accuracy of tumor tracking. Fluoroscopic images were obtained using a direct type of dynamic FPD. Image lag properties were measured without test devices according to IEC 62220-1. Modulation transfer function (MTF) and profile curves were measured on the edges of a moving tungsten plate at movement rate of 10 and 20 mm/s, covering lung tumor movement of normal breathing. A lung tumor and metal sphere with blurred edge due to image lag was simulated using the results and then superimposed on breathing chest radiographs of a patient. The moving target with and without image lag was traced using a template-matching technique. In the results, the image lag for the first frame after X-ray cutoff was 2.0% and decreased to less than 0.1% in the fifth frame. In the measurement of profile curves on the edges of static and moving tungsten material plates, the effect of image lag was seen as blurred edges of the plate. The blurred edges of a moving target were indicated as reduction of MTF. However, the target could be traced within an error of +/- 5 mm. The results indicated that there was no effect of image lag on target tracking in usual breathing speed in a radiotherapy situation. PMID- 21030797 TI - Noninvasive monitoring of radiation-induced early therapeutic response using high resolution MR imaging and proton MR spectroscopy in VX2 carcinoma. AB - The purpose of this study was to evaluate the usefulness of high-resolution MRI (HR-MRI) and proton MR spectroscopy ((1)H-MRS) for monitoring the early therapeutic response to radiotherapy. Twenty rabbits with VX2 carcinoma were divided into control (n = 8) and irradiation (n = 12) groups. The irradiation group underwent HR-MRI and (1)H-MRS using a microscopy coil at 1, 3, 7 or 14 days after irradiation. Rabbits in the control group were subjected to HR-MRI and (1)H MRS at the same time intervals. All rabbits were killed after imaging and subjected to histopathologic examinations. The diameter of necrosis by HR-MRI was then compared to that on the gross specimens. The ratios of choline/creatine (Cho/Cr) and lactate/creatine (Lac/Cr) on the tumor and necrotic area detected by in vivo (1)H-MRS were compared between the control and irradiation groups, respectively. In addition, the ratios of Cho/Cr and Lac/Cr were compared between the tumor and necrotic area in each irradiation group. A significant correlation was found between the diameter of necrosis in each sequence of HR-MRI and that in the gross specimens (r = 0.84-0.91, p = 0.03- < 0.003). The ratios of Lac/Cr in the tumors of the irradiation groups were significantly higher than those in the control groups after 1 day and 3 days of irradiation (p = 0.04, and p = 0.02). Histological analysis showed necrosis and swelling of the endothelia of capillaries and arterioles at 1 day and 3 days after irradiation. It was suggested that HR-MRI and (1)H-MRS are useful methods for monitoring the early therapeutic response to radiotherapy. PMID- 21030798 TI - Effectiveness of brain hypothermia treatment in patients with severe subarachnoid hemorrhage: comparisons at a single facility. AB - The effectiveness of hypothermia treatment for severe subarachnoid hemorrhage (SAH) was evaluated at the same facility under the same director. A total of 187 patients with SAH, 67 admitted before the introduction of hypothermia treatment in May 1999 (early cases) and 120 treated thereafter (late cases), were transported to the National Cardiovascular Center and treated in the acute phase between November 1997 and September 2001. Brain hypothermia treatment was performed in 19 patients of the 120 late cases, 10 males and 9 females aged 33-72 years (mean 57. 6 years), treated by direct surgery in 15 and endovascular surgery in 4. The indications for hypothermia treatment were age of 75 years or younger, SAH due to rupture of a cerebral aneurysm, Japan Coma Scale score of 100 or higher, and initiation of treatment within 24 hours after the onset. The body core temperature was sustained at 34 degrees C for 48 hours, rewarming was performed over 48 hours, and normothermia was maintained thereafter. The outcome, evaluated according to the modified Rankin scale (m-RS) on transfer to another hospital or after 3 months, was m-RS 3 in 1 patient, m-RS 4 in 4, m-RS 5 in 3, and death in 11. Before the introduction of hypothermia treatment (early period), 16 patients showed the indications for the treatment, and their outcomes were m RS 3 in 2, m-RS 4 in 3, m-RS 5 in 2, and death in 9. Cerebral vasospasm was important as a prognostic factor, markedly deteriorating the outcome. Hyperthermia after therapeutic hypothermia induced brain swelling and markedly affecting the outcome. Brain hypothermia treatment did not improve the outcome of severe SAH compared with the period before its introduction. The emphasis in treating severe SAH should be placed on the maintenance of normothermia to prevent brain swelling and elimination of factors that may induce cerebral vasospasm, rather than interventional hypothermia for aggressive brain protection. PMID- 21030799 TI - Poor-grade ruptured middle cerebral artery aneurysm with intracerebral hematoma: bleeding characteristics and management. AB - Poor-grade ruptured middle cerebral artery aneurysm is frequently associated with intraparenchymal hemorrhage, which is associated with high morbidity rates. We analyzed the clinical presentations and surgical strategies of 23 cases of ruptured middle cerebral artery aneurysm. Hematomas were divided into three types: temporal hematoma (7 patients), sylvian hematoma (10 patients), and frontal hematoma (6 patients). In 13 of 23 patients, preoperative brainstem symptoms suggested impeding uncal herniation. Surgical procedures included external decompression in 11 patients, simple lateral temporal lobectomy in 5, and selective uncectomy in 9. Three patients died. Favorable outcome defined as upper half of severely disabled or better in the extended Glasgow Outcome Scale was achieved in 13 patients. Patients with frontal hematomas presented with both uncal herniation and brainstem signs preoperatively, but this subgroup showed unexpectedly good recovery. Patients with sylvian hematomas had relatively poor outcomes. The present series suggests that aggressive decompression and evacuation of hematoma in the acute stage may prevent significant postoperative brain swelling, and will not compromise the treatment of vasospasm. PMID- 21030800 TI - Comparing accuracy of cerebral aneurysm size measurements from three routine investigations: computed tomography, magnetic resonance imaging, and digital subtraction angiography. AB - Modern imaging technologies, such as computed tomography (CT) angiography, magnetic resonance (MR) angiography, and digital subtraction (DS) angiography are widely used for pretreatment evaluation of cerebral aneurysms, but the relative accuracies of these modalities are unclear. This study compared the measurements of aneurysm neck and dome height and width on CT angiography, time-of-flight (TOF)-MR angiography, and DS angiography using a three-dimensional workstation. An elastic model of a side-wall aneurysm was connected to an artificial heart pulsatile circuit system. The aneurysm model was prepared using a silicone membrane of 0.6-mm thickness under normal physiological circulation parameters. Using this aneurysm model, three-dimensional TOF-MR angiography, contrast enhanced CT angiography, and DS angiography were performed. Source images were post-processed on a dedicated workstation to calculate the aneurysm size. DS angiography measurements were found to be the most accurate. In contrast, aneurysm neck sizes measured on CT angiography were significantly wider than actual values (p < 0.05) and aneurysm heights measured using TOF-MR angiography were significantly lower than actual values (p < 0.01). In this in-vitro model, at least one aneurysm dimension measured with CT angiography and with TOF-MR angiography differed significantly from actual values. Aneurysm neck width markedly affects therapeutic planning, as a wide neck requires craniotomy or endovascular treatment using an adjunctive device, so inaccuracies should be considered when aneurysm treatment is planned using modern methods of visualization. PMID- 21030801 TI - Spray-irrigation system attached to high-speed drills for simultaneous prevention of local heating and preservation of a clear operative field in spinal surgery. AB - Heat generation due to drilling during spinal surgery is potentially hazardous to nerves. Saline irrigation is often performed to prevent such local heating, but sometimes floods and obscures the operative field. We have developed a spray irrigation system for attachment to high-speed drills, which sprays saline solution with an air-jet in the direction of the surface cut by the drill. We anticipated that this air jet would create a clearer operative view by displacing excess fluid, and would also provide an added cooling effect greater than that of irrigation with saline. This study was designed to evaluate these predicted effects of the spray-irrigation system compared to conventional irrigation. A thermography study was performed to confirm the cooling effect of the spray irrigation system. A plaster board coated with adhesives was drilled at 100,000 rpm along a 10-cm line for a duration of 20 seconds. Thermograms were recorded every minute, without cooling, with irrigation, and with the spray-irrigation system. To examine the operative views, continuous drilling for a period of seconds was performed with conventional irrigation and with the spray-irrigation system. Local heating was inhibited by the spray-irrigation system to 14-30% of that with irrigation. A clear operative field was maintained during continuous drilling using the spray-irrigation system through the air-jet action of the system. The spray-irrigation system can simultaneously provide effective cooling and a clear operative field during surgical manipulations with high-speed drills. PMID- 21030803 TI - Long-term follow up of antegrade recanalization of vertebral artery dissecting aneurysm after internal trapping: case report. AB - A 34-year-old female presented with subarachnoid hemorrhage caused by the rupture of a right vertebral artery (VA) dissecting aneurysm. The affected site, including the aneurysm and parent artery, was successfully occluded with detachable coils. Follow-up angiography performed 28 days after the endovascular treatment revealed recanalization of the parent artery. We decided to treat the patient conservatively without further intervention because the aneurysm had been completely occluded. Magnetic resonance imaging showed a normal VA configuration with a minor irregularity of the affected wall at 6 years after onset. Rebleeding tends to occur during the acute stage because spontaneous healing of the dissecting vascular wall typically occurs within one month after onset. Our case suggests that additional intervention is unnecessary during the chronic stage once the aneurysm has been occluded and no further signs of the development of VA dissection are found. PMID- 21030802 TI - Surgical experience of gas-containing disk herniation. AB - Disk herniation with gas or gas-containing disk herniation (GCDH) is rare, although epidural gas is associated with the vacuum phenomenon. The clinical, radiologic, and surgical findings were retrospectively analyzed of 18 patients with GCDH. The demographic, clinical, and radiologic findings including computed tomography and magnetic resonance imaging, as well as operative methods were examined. The mean age was 64.4 years (range 51-84 years). All patients presented with acute radiculopathy or exacerbation of chronic pain associated with GCDH of the lumbar spine. All lumbar GCDHs were related to the vacuum phenomenon. Ruptured disks predominantly compressed the nerve root with gas in 17 cases, except in one with only compressed nerve root by gas without disk herniation. All patients had confirmed GCDH at surgery. All patients underwent removal of GCDH and five with another level of spinal stenosis or disk herniation underwent selective decompression. The six patients with instability underwent fusion. Visual analogue scale score of radicular pain was improved from 7.4 +/- 0.9 before surgery to 3.2 +/- 0.7 at the 3-month follow-up examination. No recurrence occurred after surgery. GCDH can occur as a space-occupying lesion in epidural space as well as a cause of radiculopathy. GCDH may indicate the source of clinical symptoms in the degenerative spine, especially combined with spinal stenosis or multiple spinal disk herniations. PMID- 21030804 TI - Internal trapping of a ruptured vertebral artery dissecting aneurysm followed by recanalization of the trapped vertebral artery without aneurysm recurrence: case report. AB - A 61-year-old man presented with a ruptured vertebral artery dissecting aneurysm manifesting as severe headache, which was treated by internal trapping, and later resulted in recanalization of the affected vertebral artery without aneurysm recurrence. Computed tomography revealed subarachnoid hemorrhage caused by a dissecting right vertebral artery aneurysm located just distal to the origin of the posterior inferior cerebellar artery. The patient underwent uneventful internal trapping. However, recanalization of the affected vertebral artery with stenosis was found on the 22nd postoperative day, apparently caused by insufficient thrombosis related to the short trapping length. No aneurysm recurrence or ischemic events were detected, so the patient was observed carefully. After 4 months, right vertebral angiography revealed that the vertebral artery was normal with no stenosis or aneurysm. Restoration of the vertebral artery without complication probably occurred by complete thrombosis of the aneurysm followed by reconstruction of the injured arterial wall. We adopted a conservative approach in this case, but additional embolization and/or stenting should be considered if high risk of rebleeding is suggested by angiographic findings, although the management of recanalization remains controversial. PMID- 21030806 TI - Carotid artery stenting in a patient with internal carotid artery stenosis and ipsilateral persistent primitive hypoglossal artery presenting with transient ischemia of the vertebrobasilar system: case report. AB - A 62-year-old man experienced transient episodes of vertigo associated with left upper extremity weakness. Cerebral angiography showed 75% right internal carotid artery (ICA) stenosis and divergence of a persistent primitive hypoglossal artery (PPHA) distal to the stenosis. The area of stenosis was at a high position and he had a past medical history of congestive heart failure, which contraindicated carotid endarterectomy (CEA). Therefore, carotid artery stenting (CAS) was performed with single distal balloon protection. The stenotic area was restored and he was discharged without suffering recurrent attacks. CAS may be an effective alternative treatment to CEA to prevent further ischemic attacks in the posterior circulation in patients with PPHA. CAS using simple embolic protection devices is possible if the distance between the distal end of the ICA stenosis and the origin of the PPHA is sufficiently long. PMID- 21030807 TI - Rapid reduction of acute subdural hematoma and redistribution of hematoma: case report. AB - An 88-year-old woman presented with acute subdural hematoma (ASDH) which showed rapid resolution on computed tomography (CT) and magnetic resonance (MR) imaging. She was transferred to our hospital after falling out of bed. On admission, she was comatose with Japan Coma Scale score of 200 and Glasgow Coma Scale score of E1V1M2. Brain CT showed a thick left frontotemporal ASDH. Conservative treatment consisted of 200 ml of glycerol administered intravenously twice a day, and maintenance in the approximately 20 degree head-up position to reduce intracranial pressure. Three days later, her consciousness recovered to Japan Coma Scale score of 30 and Glasgow Coma Scale score of E2V4M5. CT showed obvious reduction of the hematoma without brain or scalp swelling. Spinal MR imaging detected no redistribution of hematoma to the spine. The present case illustrates that rapid spontaneous reduction of ASDH may occur by redistribution of hematoma, mainly to the supratentorial subdural space because of brain atrophy. PMID- 21030808 TI - Acute epidural hematoma in a patient with Glanzmann's thrombasthenia: case report. AB - A 7-year-old girl with Glanzmann's thrombasthenia (GT) fell and hit her head against a table. Within 2 hours she began to vomit and became drowsy. On admission to our hospital her Glasgow Coma Scale score was 13. Computed tomography (CT) on admission showed acute epidural hematoma in the left posterior fossa. We administered platelets, performed emergent lateral suboccipital craniotomy, and totally removed the epidural hematoma. Postoperative CT showed no evidence of hematoma or re-bleeding. She was discharged without neurological deficits 14 days after the operation. GT is a platelet aggregation disorder due to a functional loss of platelet membrane glycoprotein IIb/IIIa. The present patient with GT underwent successful emergency craniotomy after platelet transfusion. PMID- 21030805 TI - Giant internal carotid artery aneurysm manifesting as difficulty in swallowing: case report. AB - A 66-year-old man presented with a rare case of a giant aneurysm of the internal carotid artery manifesting as difficulty in swallowing, resulting in severe malnutrition. Initial examination found a pulsating mass protruding from the posterior wall of the pharynx in the oral cavity. The patient had left hemiplegia caused by cerebral infarction one year previously. The patient underwent surgical therapy consisting of superficial temporal artery-middle cerebral artery bypass and trapping of the internal carotid artery. The pulsation of the oral mass vanished just after surgery and his difficulty in swallowing gradually improved. The patient was discharged with no new neurological deficits. The previous cerebral infarction was probably caused by an embolus from this giant aneurysm. PMID- 21030809 TI - Choroid plexus papilloma presenting with cerebrospinal fluid rhinorrhea and otorrhea: case report. AB - A 52-year-old woman presented with right rhinorrhea and right otorrhea manifesting as aural fullness for 2 years caused by a choroid plexus papilloma in the right cerebellomedullary cistern. Computed tomography and magnetic resonance imaging revealed a well defined lobulated mass at the foramen of Luschka, which extended towards the right cerebellomedullary cistern with slight dilation of the ventricular systems. The tumor was totally resected via a right lateral suboccipital approach. Histological examination revealed a choroid plexus papilloma. Postoperative course was uneventful, just after the operation rhinorrhea ceased completely, and hearing of the right ear dramatically improved. Choroid plexus papillomas rarely cause cerebrospinal fluid (CSF) rhinorrhea. Total removal of the tumor resulted in the cessation of CSF leaks. PMID- 21030810 TI - Subependymoma with prominent rosenthal fiber formation: case report. AB - A 62-year-old woman presented with a rare case of subependymoma associated with prominent Rosenthal fibers located in the left lateral ventricle manifesting as right hemiparesis and mild motor aphasia. The tumor was well demarcated and consisted of clusters of round nuclei embedded in an abundant gliofibrillary matrix with some microcysts and prominent Rosenthal fibers. Immunohistochemically, the tumor stained positively for glial fibrillary acidic protein and negatively for synaptophysin. This case of subependymoma containing Rosenthal fiber formation is very unusual. PMID- 21030811 TI - Intracranial epidermoid tumor with changes in signal intensity on magnetic resonance imaging because of non-hemorrhagic pathology: case report. AB - A 61-year-old woman presented an intracranial epidermoid tumor manifesting as dizziness and right facial hypesthesia. Magnetic resonance (MR) imaging revealed a well-defined lobulated mass in the right cerebellopontine angle as nearly isointense to the cerebrospinal fluid (CSF) on both T(1)- and T(2)-weighted images but inhomogeneously hyperintense on fluid-attenuated inversion recovery images. MR imaging performed 1 year later revealed that the tumor had significantly enlarged, and now appeared hyperintense to the CSF on T(1)- and T(2)-weighted images. The lesion was confirmed at surgery to be an epidermoid tumor filled with xanthochromic fluid. Histological examination found no evidence of hemorrhage in the resected tumor, so the changes in the MR imaging signal intensity were attributed to changes in the protein concentration of the intratumoral fluid, accumulation of debris, or some other non-hemorrhagic process. PMID- 21030812 TI - Pilomyxoid astrocytoma of the cervical spinal cord successfully treated with chemotherapy: case report. AB - A 15-month-old girl presented with a spinal pilomyxoid astrocytoma manifesting as a 3-month history of dysphagia. Magnetic resonance imaging showed an intramedullary mass of the cervical spinal cord at C1-C6 with syringobulbia. She underwent partial removal of the tumor and received postoperative chemotherapy with cisplatin and etoposide. The tumor completely responded to the treatment and has not relapsed for 64 months. Pilomyxoid astrocytoma frequently occurs in the opticohypothalamic regions but is rare in the spine. The present case suggests that surgery followed by chemotherapy with cisplatin and etoposide may be an effective therapeutic option for pilomyxoid astrocytoma of the cervical spinal cord. PMID- 21030813 TI - Myelopathy due to multilevel cervical canal stenosis with Forestier disease: case report. AB - A 56-year-old woman presented with multilevel myelopathy associated with Forestier disease (FD). The patient was hospitalized for dysphagia, bilateral shoulder pain, and progressive gait disturbance. The diagnosis was confirmed by radiography and magnetic resonance imaging which demonstrated coalescent anterior osteophyte formation extending from C2 to C7 with atlanto-axial dislocation and persistence of mobility at C3-4, and a hyperintense area in the spinal cord at the C1 and C3-4 levels on T(2)-weighted images. Dynamic radiography showed no instability at the C1 and C3-4 levels. Decompressive laminectomy of the atlas, dome-like laminectomy, and facet fusion at C3-4 were performed, resulting in symptomatic improvement. Myelopathy is very rare in patients with FD and is due to mechanical stress at the level where mobility persists. Strategic intervention should be considered based on evaluation of mobile levels and stenotic lesions. PMID- 21030814 TI - Migration of a distal ventriculoperitoneal shunt catheter into the internal jugular vein and heart through the external jugular vein: case report. AB - A 6-year-old boy had undergone ventriculoperitoneal (VP) shunt for acute hydrocephalus because of a brain tumor at the age of 11 months, and presented with vomiting and somnolence after the shunt malfunctioned 6 days after VP shunt reconstruction, during which the right external jugular vein was injured during the tunneling process and the peritoneal catheter was not fixed to the peritoneum with a purse string suture. Radiography revealed an abnormal route of the peritoneal catheter, suggesting that the distal VP shunt catheter had migrated into venous vasculature through the right external jugular vein. Computed tomography revealed that the peritoneal catheter had migrated into the internal jugular vein and the right atrium. At surgery, the peritoneal catheter was exposed through a small incision on the subclavicular region, was easily extracted from the internal jugular vein and the heart as there was no coiling or adhesion of the distal catheter to the vascular tissues, and was repositioned into the peritoneum with weak fixing between the subcutaneous tissues of the right subclavicular region and the right abdominal rectus muscle fascia as a temporary emergency measure. Peritoneal shunt migration into the internal jugular vein and the heart through the external jugular vein can be lethal because of pulmonary infarction or arrhythmia, and must be detected as soon as possible. Periodic follow-up radiography should be scheduled after VP shunt placement, even in the absence of symptoms. PMID- 21030815 TI - Endoscopic management of a traumatic meningo-encephalocele through a planum sphenoidale defect: case report. AB - A 37-year-old man involved in a motor vehicle accident was admitted to our hospital with disturbed consciousness. Computed tomography (CT) showed an acute, right-sided epidural hematoma and pneumocephalus. Emergency evacuation of the acute epidural hematoma was carried out, and his condition gradually recovered. However, cerebrospinal fluid (CSF) rhinorrhea continued despite conservative treatment. Three-dimensional reconstructed CT revealed a bone defect, which was approximately 20 mm in size, in the planum sphenoidale and tuberculum sellae, and magnetic resonance imaging demonstrated a traumatic meningo-encephalocele through the defect, with CSF collection in the sphenoid sinus. Endoscopic endonasal transsphenoidal surgery was performed. The 9-mm diameter dural defect was clearly visualized in the sphenoid sinus and was reconstructed with a combination of suturing and overlay with abdominal fascia, and absorbable polyglycolic acid felt. The CSF leakage from a traumatic meningo-encephalocele through the planum sphenoidale was successfully repaired by endoscopic endonasal surgery. Thorough preoperative evaluation of the feasibilities of the endoscopic and transcranial approaches should be based on the preoperative identification of the fistula, the bone defect, and vital structures. PMID- 21030816 TI - Small Onodi cell mucocele causing chronic optic neuropathy: case report. AB - A 45-year-old woman presented with a rare case of small isolated Onodi cell mucocele manifesting as unilateral chronic optic neuropathy. The patient complained of gradual visual disturbance of her left eye with no other neurological abnormalities. Neuroimaging examinations showed a small cystic lesion located in the left posterior ethmoid extending into the anterior clinoid process. Surgery via the pterional epidural approach revealed a cystic lesion containing mucinous fluid isolated in the anterior clinoid process. Total removal of the lesion combined with unroofing of the left optic canal resulted in relief of the patient's symptom. Histological examination showed the lesion was a mucocele. Based on the radiological and surgical findings together with the histological examination, the final diagnosis was Onodi cell mucocele. Such small Onodi cell mucocele can cause optic neuropathy but is extremely unusual. PMID- 21030817 TI - Superficial temporal artery to middle cerebral artery double bypass via a small craniotomy: technical note. AB - Frontotemporal craniotomy is usually necessary to perform superficial temporal artery (STA)-middle cerebral artery (MCA) double bypass for cerebrovascular occlusive disease. This report describes a less invasive technique of double bypass through a small craniotomy with minimum skin incision. Thirty-four consecutive patients underwent an elective STA-MCA double bypass via a small craniotomy from January 2006 to October 2009. The parietal and frontal branches of the STA were divided through a minimum linear or y-shaped skin incision, and these branches were anastomosed to the supra- and infrasylvian portions of the MCA. No periprocedural complication such as subdural hematoma or cutaneous necrosis occurred. Postoperative cerebral angiography within 6 months showed that the bypasses were patent in all 34 patients. Double STA-MCA bypass via a small craniotomy might be less invasive, especially for patients at high risk for postoperative hemorrhagic complication or cutaneous necrosis. PMID- 21030818 TI - Myocardial fiber shortening in the circumferential direction produces left ventricular wall thickening during contraction. AB - When one bends the elbow by shortening of the biceps, a knot of muscle is observed in his or her upper arm, indicating that muscle shortening is converted to muscle standing in the perpendicular direction due to the incompressibility of skeletal muscle. A similar mechanism may work in the thickening process of the left ventricular (LV) wall. Although myocardial fibers of the left ventricle shorten by about 20% along the fiber direction when they contract, thickening of the LV wall during contraction often exceeds 50%. Thus, the aim of the present study was to clarify the mechanism by which myocardial fiber shortening produces such remarkable thickening of the LV wall. We hypothesized that myocardial fiber shortening in the circumferential direction causes myocardial transformation perpendicular to the fiber direction, thereby producing LV wall thickening. We evaluated this hypothesis using an incompressible model of the LV wall. In 15 healthy male volunteers (38+/-13 years), we calculated theoretical peak thickening values of the inner and outer LV wall layers and compared them with directly measured peak thickening values using Doppler strain imaging at the corresponding areas. The theoretical peak thickening and directly measured peak thickening were >60% in the LV inner layer. The theoretical peak thickening was correlated with the directly measured peak thickening in the inner (r=0.75, p<0.05) and outer (r=0.61, p<0.05) layers. We conclude that shortening of LV circumferential myocardial fiber and incompressibility of myocardium produce LV wall thickening during contraction. PMID- 21030820 TI - Microencapsulation of live probiotic bacteria. AB - Scientific research regarding the use of live bacterial cells for therapeutic purposes has been rapidly growing over the years and has generated considerable interest to scientists and health professionals. Probiotics are defined as essential live microorganisms which, when administered in adequate amounts, confer a health benefit on the host. Due to considerable beneficial health effects, these microorganisms are increasingly incorporated into the dairy products; however, many reports demonstrated their poor survival and stability. Their survival in the gastrointestinal (GI) tract is also questionable. To overcome these problems, microencapsulation techniques are currently receiving considerable attention. This review describes the importance of live probiotic bacterial microencapsulation using an alginate microparticulate system and presents the potentiality of various coating polymers such as chitosan and polylysine for improving the stability of this microencapsulation. PMID- 21030819 TI - Identification and characteristics of microRNAs with altered expression patterns in a rat model of abdominal aortic aneurysms. AB - Abdominal aortic aneurysm (AAA) is a lethal disease, occurring mostly in men more than 65 years of age. Until recently, the pathogenesis of AAA remains poorly understood. MicroRNAs (miRNAs) are a novel class of endogenous small non-coding RNAs that play important roles in diverse biological and pathological processes including cardiovascular diseases. However, their biological roles in AAA formation have not been elucidated. In this study, we employed oligonucleotide microarrays to detect and compare miRNA expression profiles in a rat model of AAA. The abdominal aorta was exposed and incubated for 20 min with saline supplemented with calcium chloride and collagenase. After 28 days, the treated aortas were evaluated by digital measurement and angiography. A 50% increase over the normal diameter is considered as AAA. Our results revealed a set of differentially expressed miRNAs, with 10 significantly up-regulated and 5 significantly down-regulated miRNAs in AAA tissues. Four miRNAs (miR-19a, miR 19b, miR-132, and miR-221) were randomly selected for validation using real-time RT-PCR. Functional annotations of all putative targets of differentially expressed miRNAs via bioinformatics approaches revealed that predicted targets were highly enriched and involved in several key signaling pathways important for AAA formation, including pathways in cancer and signaling pathways involving mitogen-activated protein kinase, Wnt, neurotrophin, and ErbB. In summary, this study indicates that miRNAs might contribute to AAA formation probably by affecting multiple target genes and signaling pathways, which is expected to provide new clues to develop targeted therapies against this calamitous disease. PMID- 21030821 TI - Isolation of a novel freshwater agarolytic Cellvibrio sp. KY-YJ-3 and characterization of its extracellular beta-agarase. AB - A novel agarolytic bacterium KY-YJ-3, producing extracellular agarase, was isolated from the freshwater sediment of the Sincheon River in Daegu, Korea. On the basis of gram-staining data, morphology, and phylogenetic analysis of the 16S rDNA sequence, the isolate was identified as Cellvibrio sp. By ammonium sulfate precipitation followed by Toyopearl QAE-550C, Toyopearl HW-55F, and Mono-Q column chromatography, the extracellular agarase in the culture fluid could be purified 120.2-fold with yield of 8.1%. The specific activity of the purified agarase was 84.2 U/mg. The molecular mass of the purified agarase was 70 kDa as determined by dodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The optimal temperature and pH of the purified agarase were 35 degrees C and pH 7.0, respectively. The purified agarase failed to hydrolyze the other polysaccharide substrates, including carboxymethyl (CM)-cellulose, dextran, soluble starch, pectin, and polygalacturonic acid. Kinetic analysis of the agarose-hydrolysis catalyzed by the purified agarase using thin layer chromatography (TLC) exhibited that the main products were neoagarobiose, neoagarotetraose, and neoagarohexaose. These results demonstrated that the newly isolated freshwater agarolytic bacterium KY-YJ-3 was a Cellvibrio sp., and could produce an extracellular beta agarase, which hydrolyzed agarose to yield neoagarobiose, neoagarotetraose, and neoagarohexaose as the main products. PMID- 21030822 TI - Rheinheimera aquatica sp. nov., an antimicrobial activity producing bacterium isolated from freshwater culture pond. AB - A bacterial strain designated GR5(T) was isolated from freshwater culture pond in Taiwan during the screening of bacteria for antimicrobial compounds and characterized using the polyphasic taxonomic approach. Strain GR5(T) was Gram negative, aerobic, greenish-yellow colored, rod-shaped, and motile by means of a polar single flagellum. Growth occurred at 10-40 degrees C (optimum, 35 degrees C), at pH 7.0-8.0 (optimum pH 8.0) and with 0-2.0% NaCl (optimum, 0.5-1.0%). The major fatty acids were C(16:1) omega7c (36.3%), C(16:0) (16.6%), C(12:0) 3-OH (12.5%) and C(18:1) omega7c (9.1%). The major respiratory quinone was Q-8. The DNA G+C content of the genomic DNA was 51.9 mol%. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain GR5(T) belonged to the genus Rheinheimera and its most closely neighbours were Rheinheimera texasensis A62 14B(T) and Rheinheimera tangshanensis JA3-B52(T) with sequence similarities of 98.1 and 97.5%, respectively. The sequence similarities to any other recognized species within Gammaproteobacteria were less than 96.5%. The mean level of DNA DNA relatedness between strain GR5(T) and R. texasensis A62-14B(T), the strain most closely related to the isolate, was 26.5 +/- 7.6 %. On the basis of the phylogenetic and phenotypic data, strain GR5(T) should be classified as representing a novel species, for which the name Rheinheimera aquatica sp. nov. is proposed. The type strain is GR5(T) (= BCRC 80081(T) = LMG 25379(T)). PMID- 21030823 TI - Change of Bacillus cereus flavonoid O-triglucosyltransferase into flavonoid O monoglucosyltransferase by error-prone polymerase chain reaction. AB - The attachment of sugar to flavonoids enhances their solubility. Glycosylation is performed primarily by uridine diphosphate-dependent glycosyltransferases (UGTs). The UGT from Bacillus cereus, BcGT-1 transferred three glucose molecules into kaempferol. The structural analysis of BcGT-1 showed that its substrate binding site is wider than that of flavonoid monoglucosyltransferase of plant. In order to create monoglucosyltransferase from BcGT-1, error-prone polymerase chain reaction (PCR) was performed. We analyzed 150 clones. Among them, two mutants generated only kaempferol O-monoglucoside, albeit with reduced reactivity. Unexpectedly, the two mutants harbored mutations in the amino acids located outside of the active sites. Based on the modeled structure of BcGT-1, it was proposed that the local change in the secondary structure of BcGT-1 caused the alteration of triglucosyltransferase into monoglucosyltransferase. PMID- 21030824 TI - Fungicidal effect of prenylated flavonol, papyriflavonol A, isolated from Broussonetia papyrifera (L.) vent. against Candida albicans. AB - Papyriflavonol A (PapA), a prenylated flavonoid (5,7,3',4'-tetrahydroxy-6,5'-di (r,r-dimethylallyl)-flavonol), was isolated from the root barks of Broussonetia papyriferra. Our previous study showed that PapA has a broad-spectrum antimicrobial activity against pathogenic bacteria and fungi. In this study, the mode of action of PapA against Candida albicans was investigated to evaluate PapA as antifungal agent. The minimal inhibitory concentration (MIC) values were 10~25 microgram/ml for C. albicans and Saccharomyces cerevisiae, gram-negative bacteria (Escherichia coli and Salmonella typhimurium) and gram-positive bacteria (Staphylococcus epidermidis and Staphylococcus aureus). The kinetics of cell growth inhibition, scanning electron microscopy, and measurement of plasma membrane florescence anisotrophy revealed that the antifungal activity of PapA against C. albicans and S. cerevisiae is mediated by its ability to disrupt the cell membrane integrity. Compared with amphotericin B, a cell membrane disrupting polyene antibiotic, the hemolytic toxicity of PapA was negligible. At 10~25 microgram/ml of MIC levels for the tested strains, the hemolysis ratio of human erythrocytes was less than 5%. Our results suggest that PapA could be a therapeutic fungicidal agent having a broad spectrum antimicrobial agent. PMID- 21030825 TI - Acidophilic tannase from marine Aspergillus awamori BTMFW032. AB - Aspergillus awamori BTMFW032, isolated from sea water, produced tannase as extracellular enzyme under submerged culture conditions. Enzyme with a specific activity of 2761.89 IU/mg protein, a final yield of 0.51 %, and a purification fold of 6.32 was obtained after purification to homogeneity by ultrafiltration and gel filtration. SDS-PAGE analyses under non- reducing and reducing conditions yielded a single band of 230 kDa and 37.8 kDa, respectively, indicating presence of six identical monomers. pI of 4.4 and 8.02 % carbohydrate content in the enzyme were observed. Optimal temperature was 30oC, although the enzyme was active at 5-80 oC. Two pH optima, pH 2 and pH 8, were recorded and the enzyme was stable only at pH 2.0 for 24 h. Methylgallate recorded maximal affinity and K(m) and V(max) were recorded, respectively, as 1.9 X 10-3 M and 830 micronmol/min. Impact of several metal salts, solvents, surfactants, and typical enzyme inhibitors on tannase activity were determined to establish the novelty of the enzyme. Gene encoding tannase isolated from A. awamori is 1.232 kb and nucleic acid sequence analysis revealed an open reading frame consisting of 1122 bp (374 amino acids) of one stretch in -1 strand. In-silico analyses of gene sequences and comparison with reported sequences of other species of Aspergillus indicated that the acidophilic tannase from marine A. awamori is differs from that of other reported species. PMID- 21030826 TI - Purification and characterization of a thermostable xylanase from Fomitopsis pinicola. AB - An extracellular xylanase was purified to homogeneity by sequential chromatography of Fomitopsis pinicola culture supernatants on a DEAE-sepharose column, a gel filtration column, and then on a MonoQ column with fast protein liquid chromatography. The relative molecular weight of F. pinicola xylanase was determined to be 58 kDa by sodium dodecylsulfate polyacrylamide gel electrophoresis and by size exclusion chromatography, indicating that the enzyme is a monomer. The hydrolytic activity of the xylanase had a pH optimum of 4.5 and a temperature optimum of 70 degreesC. The enzyme showed t(1/2) value of 33 h at 70 degrees C and catalytic efficiency (k(cat) = 77.4 s-1, k(cat)/K(m) = 22.7 mg/ml/s) for oatspelt xylan. Its internal amino acid sequences showed a significant homology with hydrolases from glycoside hydrolase (GH) family 10, indicating that the F. pinicola xylanase is a member of GH family 10. PMID- 21030827 TI - Synthesis of an amphiphilic poly(gamma-glutamic acid)-cholesterol conjugate and its application as an artificial chaperone. AB - A poly(gamma-glutamic acid) (gammaPGA)-cholesterol conjugate was synthesized and the properties of an aqueous solution were evaluated. The conjugate showed amphiphilic nature derived from the hydrophilic gammaPGA backbone and the hydrophobic cholesterol side chain. The conjugate spontaneously formed nanoparticles in the aqueous solution of the low concentration, and the high concentration resulted in the formation of the physical gel. By utilizing the self-aggregating properties of the conjugate in water, an artificial chaperone was developed. The complex of protein with the nanoparticles of the conjugate was formed and the protein was released upon the dissociation of the nanoparticles by the addition of beta-cyclodextrin. For denatured carbonic anhydrase, the activity was recovered in the artificial chaperone of the nanoparticle conjugate. PMID- 21030828 TI - The orientation-dependent expression of angiostatin-endostatin hybrid proteins and their characterization for the synergistic effects of antiangiogenesis. AB - Two angiostatic fusion proteins (hAE and hEA) of human angiostatin (hAS) and endostatin (hES) proteins differed in tandem connection manner were constructed and evaluated for synergistic anti-angiogenic effects. The 65 kDa secreted fusion proteins from Pichia pastoris expression were verified by mass-spec analysis and western blotting assay. Luciferase reporter gene assay using VEGF promoter revealed that angiostatin-endostatin fusion protein (hAE) and its corresponding fusion gene delivery on Human Microvascular Endothelial Cells (HMEC-1) resulted in more potent synergistic anti-angiogenic effects than endostatin-angiostatin fusion protein (hEA). These facts suggest that the orientation of fusion genes between hAS and hES might be an important factor for developing therapeutic proteins. PMID- 21030829 TI - Chelation of calcium ions by poly(gamma-glutamic acid) from Bacillus subtilis(chungkookjang). AB - Many studies have clarified that poly(gamma-glutamic acid) (PGA) increases the solubility of Ca(2+), suggesting that PGA enhances calcium absorption in small intestine. However, there has been no report on the specific interaction between PGA and Ca(2+) in water. We studied the aqueous solution properties of PGA calcium salt (PGA-Ca complex). The chelating ability and binding strength of PGA for Ca(2+) were evaluated. PGA-Ca complex was soluble in water in contrast with the insolubility of poly(acrylic acid) (PAA) calcium salt and the chelating ability of PGA for Ca(2+) was almost the same than that of PAA. The globular conformation of PGA-Ca complex in water was estimated by SEC and viscosity measurements. The chelation of PGA for Ca(2+) was examined by 1H NMR. The present study showing the characteristics of PGA-Ca complex will provide useful information of the calcium absorption by PGA in vivo. PMID- 21030830 TI - Biodegradation of di-n-butyl phthalate by Rhodococcus sp. JDC-11 and molecular detection of 3, 4-phthalate dioxygenase gene. AB - Rhodococcus sp. JDC-11, capable of utilizing di-n-butyl phthalate (DBP) as the sole source of carbon and energy, was isolated from sewage sludge and confirmed mainly based on 16S rRNA gene sequence analysis. The optimum pH, temperature, and agitation rate for DBP degradation by Rhodococcus sp. JDC-11 was 8.0, 30 degrees C, and 175 rpm, respectively. In addition, the effect of glucose concentration on DBP degradation indicated that low concentration of glucose inhibited the degradation of DBP while high concentrations of glucose increased its degradation. Meanwhile, the substrates utilization test showed that JDC-11 could also utilize other phthalates. Furthermore, the major metabolites of DBP degradation were identified as mono-butyl phthalate and phthalic acid by gas chromatography-mass spectrometry and the metabolic pathway of DBP degradation by Rhodococcus sp. JDC-11 was tentatively speculated. Using a set of new degenerate primer, partial sequence of the 3, 4-phthalate dioxygenase gene was obtained from the strain. Sequence analysis revealed that the phthalate dioxygenase gene of JDC 11 was highly homologous to the large subunit of phthalate dioxygenase from Rhodococcus coprophilus strain G9. PMID- 21030831 TI - Antimicrobial susceptibility of coagulase-negative staphylococci isolated from bovine mastitis between 2003 and 2008 in Korea. AB - A total of 1,444 coagulase-negative staphylococci (CNS) isolates from bovine mastitic milk samples collected during 2003-2008 in Korea were identified to the species level. Of 14 species identified, S. simulans, S. haemolyticus, and S. sciuri accounted for over 60% of the isolates. All the CNS isolates were tested for susceptibility to eight antimicrobials commonly used in dairy cattle. With a few exceptions, similar resistance patterns were observed among the CNS species: penicillin and ampicillin showed the lowest activity while amikacin, cephalothin, and gentamycin were highly effective. About 39% (557/1,444) of the CNS isolates were pan-susceptible, while 12% (175/1,444) showed resistance to four or more antimicrobials tested. PMID- 21030832 TI - Comparative analysis of the multiple test methods for the detection of Pandemic Influenza A/H1N1 2009 virus. AB - Accurate and rapid diagnosis of Pandemic Influenza A/H1N1 2009 virus (H1N1 2009) infection is important for the prevention and control of influenza epidemics and the timely initiation of antiviral treatment. This study was conducted to evaluate the performance of several diagnostic tools for the detection of H1N1 2009. Flocked nasopharyngeal swabs were collected from 254 outpatients of suspected H1N1 2009 during October 2009. This study analyzed the performances of RealTime ready Inf A/H1N1 Detection Set (Roche), Influenza A (H1N1) Real-Time Detection Kit (Bionote), Seeplex Influenza A/B OneStep Typing set (Seeplex reverse transcriptase PCR [RT-PCR]), BinaxNow Influenza A & B test kit (Binax rapid antigen test [RAT]) and SD BIOLINE Influenza Ag kit (SD RAT). Roche and Bionote real-time RT-PCR showed identical results for the H1N1 2009 hemagglutinin gene. Compared with real-time RT-PCR, the sensitivities and specificities were 83.7% and 100% for Seeplex RT-PCR, 64.5% and 94.7% for Binax RAT, and 69.5% and 100% for SD RAT. The sensitivities of Seeplex RT-PCR, Binax RAT and SD RAT in patients aged over 21 years were 73.7%, 47.4% and 57.9%, respectively. The sensitivities of Seeplex RT-PCR, Binax RAT and SD RAT on the day of initial symptoms were mostly lower (68.8%, 56.3% and 31.3%, respectively). In conclusion, multiplex RT-PCR and RAT for the detection of H1N1 2009 were significantly less sensitive than real-time RT-PCR. Also, a negative RAT may require more sensitive confirmatory assays, because it cannot be ruled out from influenza infection. PMID- 21030833 TI - Genetic characterization of atypical Shigella flexneri isolated in Korea. AB - Three types of serotypically atypical Shigella flexneri strains were isolated from 2007 to 2008 in patients at the Korea National Institute of Health (NIH). These strains were characterized and compared with serologically typical S.flexneri. One type of strain either displayed nonreacting typing or grouping sera, reacting strongly only with polyB antisera, which indicates this strain is S. flexneri (polyB:un). The second type displayed reactions with one of the typing sera (IV) and did not bind any grouping sera (IV:un). The remaining type of strain displayed a plural agglutination pattern, reacted with one typing sera (II), and bound with two grouping sera (II:(3)4,7(8)). Among these atypical strains IV:un and II:(3)4,7(8) strains showed higher multi-antibiotic resistance in ampicillin, streptomycin, and trimethoprim-sulfamethoxazole than typical strains. Furthermore, all II:(3)4,7(8) strains harbored integrons. This study suggests that these multiple antibiotic-resistant atypical S. flexneri are new subserotypes of S.flexneri that await further serological classification. PMID- 21030834 TI - Quantitative detection of residual E. coli host cell DNA by real-time PCR. AB - E. coli has been widely used as a host system to manufacture recombinant proteins for human therapeutic use. Among impurities to be eliminated during the downstream process, residual host cell DNA is a major interest for safety. Residual E. coli host cell DNA in the final products are usually determined using conventional slot blot hybridization assay or total DNA Threshold assay, although these methods are time consuming, expensive, and relatively insensitive. Therefore a sensitive real-time PCR assay for specific detection of residual E. coli DNA was developed and compared with slot blot hybridization assay and Threshold assay to validate the overall capability of these methods. Specific primer pair for amplification of the E. coli 16S rRNA gene was selected to improve the sensitivity, and E. coli host cell DNA was quantified by use of SYBR Green 1. The detection limit of real-time PCR assay in the optimized condition was calculated to be 0.042 pg genomic DNA, which is much higher than those of slot blot hybridization assay and Threshold assay of which detection limit were 2.42 and 3.73 pg genomic DNA, respectively. The real-time PCR assay was validated to be more reproducible, accurate, and precise than slot blot hybridization assay and Threshold assay. The real-time PCR assay may be a useful tool for quantitative detection and clearance validation of residual E. coli DNA during the manufacturing process for recombinant therapeutics. PMID- 21030836 TI - The impact of molecular biology on allergen immunotherapy. PMID- 21030837 TI - Current world literature. PMID- 21030839 TI - Forearm fractures in children and bone health. AB - PURPOSE OF REVIEW: Summary highlighting the evidence that bone health may affect forearm fracture risk in children. RECENT FINDINGS: Although the incidence of other fractures and injuries are decreasing, the incidence of forearm fractures is increasing in otherwise healthy children. There is a growing volume of research that forearm fracture risk in children may be related to deficiencies in parameters of bone health. Available evidence of this relationship was summarized and included direct links to bone health (measurement of bone properties), indirect links to bone health (diet, vitamin D status, BMI), and genetic analyses. SUMMARY: There is consistent and convincing evidence of an association between bone mineral density and forearm fracture risk in children. Studies of calcium intake and supplementation are less extensive in scope but suggest that effects of calcium deficiency on the radius may contribute to childhood forearm fracture risk. Forearm fracture risk in obese children is likely to reflect a combination of suboptimal bone health status and behavioral characteristics. Published data on the role of vitamin D status and genetic factors are limited but merit further consideration. Further investigation is needed to better understand the factors contributing to forearm fracture risk in children and translate this knowledge into effective clinical prevention and practice. PMID- 21030840 TI - Renal bone disease. AB - PURPOSE OF REVIEW: Renal osteodystrophy is a complex disorder of bone associated with chronic kidney disease (CKD). Disturbances in mineral metabolism, which include, phosphate retention, hypocalcemia, vitamin D deficiency, and hyperparathyroidism develop early in the progression of CKD. The Kidney Disease: Improving Global Outcomes (KDIGO) has proposed a new classification system to understand the complex pathophysiology in mineral metabolism and bone disease. Understanding this pathophysiology has become especially important, as recent evidence has suggested that disordered mineral metabolism is associated with increased cardiovascular mortality and morbidity in patients with CKD. RECENT FINDINGS: This review discusses the effect of these disturbances on the skeleton and how they result in altered bone structure and turnover. The degree of hyperparathyroidism appears to affect bone turnover; however, bone biopsies appear to be the only definitive method to specifically diagnose the bone lesion. SUMMARY: This review will assist the clinician in the early identification of patients at risk of renal osteodystrophy. Therapeutic strategies could then be employed to prevent and correct these disturbances in mineral metabolism and, thus, avoid patient morbidity. PMID- 21030841 TI - Current world literature. PMID- 21030843 TI - Challenges facing infectious diseases physicians today. Editorial comment. PMID- 21030844 TI - Bibliography. Antimicrobial agents. Current world literature. PMID- 21030846 TI - Do resuscitation-related injuries kill infants and children? PMID- 21030847 TI - Analysis of pituitary lesions in fatal closed head injury. AB - We analyzed forensic autopsy findings of 66 consecutive patients with fatal closed head injury who survived up to 48 days after trauma to ascertain the causal factors and the time course of development of posttraumatic pituitary lesions. Pituitary lesions were identified in 27 patients. In patients with pituitary lesions, posterior lobe hemorrhage was observed in 21 patients, followed by anterior lobe hemorrhage in 10 patients and anterior lobe infarct in 7 patients. Comparisons between patients with and without pituitary lesions showed that falls and subdural hematoma were significantly frequent in patients with pituitary lesions. Immunohistochemistry of neurophysin showed increased immunoreactivity in the hypothalamus of patients with pituitary lesions and brain edema, providing morphologic evidence of pituitary dysfunction. Hemorrhage in the anterior or posterior lobe was identifiable in patients with short survival periods, whereas infarct in the anterior lobe appeared in patients surviving at least 14 hours. These data further our understanding of the mechanisms of pituitary dysfunctions and help in the estimation of the survival period after head trauma. PMID- 21030848 TI - Unusual skin lesions mimicking bruises caused by Pseudomonas septicemia secondary to undiagnosed peripheral T-cell lymphoma in a young woman. AB - We present a case of a 30-year-old woman with learning difficulties who was found dead at home by her mother. Her body was partially naked and covered in a number of unusual skin lesions with a targetoid appearance with red erythematous centers and well-delineated halos of pallor. These lesions were initially thought to be bruises by the police and by a forensic postmortem instigated. Postmortem examination also identified hepatosplenomegaly, severe lymphadenopathy, and focal patchy colonic ulceration. Histologic examination of the skin and bowel ulcers showed the lesions to be areas of infarction caused by Pseudomonas aeruginosa vasculitis. Pseudomonas was also cultured from the swabs of the abdomen, the spleen, and the blood cultures. Histologic findings of the lymph nodes showed complete effacement of the normal architecture by a population of pleomorphic small lymphoid cells. Immunohistochemistry confirmed the predominant cell type to be T-cells. The diagnosis of peripheral T-cell lymphoma was made. The cause of death was given as Pseudomonas septicemia secondary to immunocompromise resulting from the undiagnosed peripheral T-cell lymphoma. The pathogenesis of Pseudomonas and its association with malignancy is discussed along with a brief review of peripheral T-cell lymphomas. This case report demonstrates the characteristic macroscopic appearance of cutaneous Pseudomonas-associated lesions and how they can be misinterpreted as bruises. PMID- 21030849 TI - Sudden infant death syndrome: diagnostic practices and investigative policies, 2004. AB - Using a 2004 population-based survey of all US medical examiner and coroner offices, we examined the characteristics of offices accepting an infant death case and calculated the percentage of offices that had death scene investigation or autopsy policies for the investigation of sudden unexpected infant death (SUID). We also calculated the percentage of offices that used and did not use sudden infant death syndrome (SIDS) as a cause of death, and we compared differences in characteristics among those offices.Of medical examiner and coroner offices, 52% did not report an infant death in 2004. Of the 7957 infant deaths reported, 43% occurred in jurisdictions that experienced 1 or 2 infant deaths. Of the offices that used SIDS as a classification, 34% did not have policies for conducting death scene investigations and autopsies for SUID. At least 5% of offices that reported an infant death did not use SIDS as a cause of death classification. These findings have important implications for understanding recent trends in SIDS and SUID. Supporting the implementation of national standards for investigating and certifying infant deaths could provide guidelines for consistent practices in medical examiner and coroner offices. PMID- 21030850 TI - A 10-year epidemiologic review of homicide cases in children younger than 5 years in Fulton County, GA: 1996-2005. AB - The primary purpose of this study was to present the epidemiologic review of homicide deaths certified by the Fulton County Medical Examiner's Office from January 1, 1996 through December 31, 2005 in children younger than 5 years. The secondary purpose of this study was to determine if the observed cases of homicide deaths among children younger than 5 years in Fulton County are significantly greater than expected when compared with those in the State of Georgia. For purposes of this study, only homicide deaths of Fulton County residents were included. The authors reviewed all homicide cases in children younger than 5 years: infancy (<1 year) and early childhood (1-4 years). chi values were calculated using Epi Info (version 3.4.1; Centers for Disease Control and Prevention, Atlanta, Ga) to determine differences in homicide among age group, race, and sex variables. In addition, a chi test at the alpha level of 0.05 was done to determine if the observed cases of homicide deaths among children younger than 5 years in Fulton County were significantly greater than expected when compared with those in the State of Georgia. There were 49 homicide cases in children younger than 5 years identified over this 10-year period. The yearly distribution of these 49 homicide deaths ranged from 1 death in 2003 to 9 deaths in 2004. Most of the patients were male (n=29, 59.2%) and black (n=44, 89.8%). Between infancy and early childhood cases, homicide victims were nearly equally divided between the 2 groups. However, chi values showed that decedents younger than 5 years are more likely to have died of homicide compared with decedents 5 years or older (odds ratio [OR], 1.74; 95% confidence interval [CI], 1.29-2.35). Black decedents younger than 5 years are more likely to have died of homicide compared with other races (OR, 3.21; 95% CI, 1.21-9.28). Male and female decedents are equally at risk to have died of homicide (OR, 1.14; 95% CI, 0.61 2.11). The authors also determined that the total homicide risk for children younger than 5 years in Fulton County during the years 1996 to 2005, at the alpha level of 0.05, is 1.8 relative to the state. Brain injury was the primary cause of death in most cases (n=23, 46.9%). Although this study was unable to collect information on the victim's suspect/offender characteristics, it was noted that only 37% of the cases (n=18) went to trial. Most homicide investigations were under the Atlanta police jurisdiction (n=28, 57.1%). Results from this study may assist local and state government officials in recognizing the epidemiologic characteristics of children at risk to help them allocate limited resources efficiently and implement preventive measures to at-risk populations effectively. PMID- 21030851 TI - The methadone epidemic: methadone-related deaths on the rise in Vermont. AB - The prevalence of methadone-related overdose deaths is increasing worldwide and has been a topic of recent debate. Methadone-related deaths, to this point, have not been systematically reviewed in the state of Vermont. All of the methadone related fatalities from 2001 to 2006 (total, 76 cases), which were examined by the Vermont Office of the Chief Medical Examiner were retrospectively reviewed. The mean age of the decedents was 36 years (range, 16-74 years), and 72% were male. The manners of death were classified as follows: 84% accident, 12% undetermined, and 4% suicide. The mean level of methadone was 457 ng/mL (range, 50-3793 ng/mL). The substances causing death were determined to be methadone alone in 26 (34%), methadone with only other prescribed medications in 29 (38%), methadone with only illicit drugs (excluding tetrahydrocannabinol) in 13 (17%), methadone with both illicit and prescribed medications in 5 (7%), and methadone with ethanol in 3 (4%). The methadone was obtained by illegal diversion (sale, gift, or theft) in 67% of cases. In the remaining cases (33%), the methadone was obtained by physician's prescription for chronic pain (60%), acute pain or injury (8%), methadone maintenance therapy for heroin dependence (8%), and unknown reasons (24%). The number of overdose deaths has increased 4-fold from 2001 (17 deaths) to 2006 (79 deaths). The proportion of methadone-related deaths has increased by 300% from 2001 (0.6% of reported deaths, 12% of overdose deaths) to 2006 (3% of reported deaths, 37% of overdose deaths). Methadone maintenance therapy for heroin dependence in our population comprises an insignificant number of the methadone-related deaths (3% of the decedents). In Vermont, the populations most at risk are those taking methadone for chronic pain and those obtaining diverted methadone for abuse. Education of clinicians regarding the increasing number of methadone-related deaths, the potential for abuse and diversion, and the pharmacokinetics of methadone may help halt this epidemic and reduce the number of fatalities from this drug. PMID- 21030852 TI - Fatal bronchial asthma with bilateral lung collapse. AB - Fatal bronchial asthma is classically characterized in pathology textbooks and journal articles as associated with lung hyperinflation at autopsy. The following is a report of a case of fatal bronchial asthma associated instead with bilateral lung collapse. This manifestation of asthma at autopsy has not been previously reported, to my knowledge. A 31-year-old man with a history of recurrent asthma was found in an unresponsive state in his automobile after a low-speed collision. Medical personnel during the resuscitation noted a decrease in breath sounds bilaterally and some wheezing. There was no escaping air with needle thoracostomies at the outset. Cardiac monitoring demonstrated pulseless electrical activity during most of the 30-minute resuscitation attempt. An autopsy disclosed collapsed lungs bilaterally. Microscopic examination of the lungs disclosed the characteristic histopathologic features of bronchial asthma. PMID- 21030854 TI - Pancoast's syndrome secondary to infectious etiologies: a not so uncommon occurrence. AB - Pancoast's syndrome includes Horner's syndrome, atrophy of the hand muscles and shoulder, axilla or arm pain. This syndrome is caused by an apical thoracic lesion, most commonly a bronchogenic carcinoma, which invades the brachial plexus roots and the cervicothoracic sympathetic chain. Several nonmalignant causes are documented in the literature with infection being one. After a case of Pancoast syndrome caused by a methicillin-sensitive Staphylococcus aureus empyema, we began a systematic search of the literature to identify case reports/series of Pancoast syndrome secondary to infection. Our search was limited to the English language and performed using MEDLINE. Thirty-one cases of Pancoast's syndrome secondary to infectious causes were found in our review of the literature. The infectious causes identified were bacterial, fungal and parasitic organisms; however, no single organism could be identified as the most prevalent. Our review represents the most complete summation of individual case reports on this subject and highlights clinical characteristics of each presentation and the organisms that were encountered. This number of cases of Pancoast's syndrome secondary to infectious causes indicates that this association may be more common than previously reported. PMID- 21030855 TI - Subarachnoid hemorrhage in a patient with Abiotrophia defectiva endocarditis. AB - Endocarditis caused by Abiotrophia accounts for 5% of all cases of infective endocarditis (Roberts et al, Rev Infect Dis. 1979;1:955-66) and 5% to 6% of all cases of streptococcal endocarditis (Bouvet, Eur Heart J. 1995;16(suppl B):24-7; Brouqui et al, Clin Microbiol Rev. 2001;14:177-207). This endocarditis is associated with a high rate of embolization and treatment failure (Bouvet, Eur Heart J. 1995;16(suppl B):24-7). Neurological complications occur in 20% to 40% of all cases of infective endocarditis (Ossorio et al, Hosp Physician. 2003;39:21 4). Subarachnoid hemorrhage is a rare but devastating neurological complication. The authors presented a case of massive fatal subarachnoid hemorrhage in a patient with Abiotrophia defectiva endocarditis. To our knowledge, there are only 2 reported cases of mycotic aneurysms in Abiotrophia endocarditis, 1 of which was associated with subarachnoid hemorrhage (Leonard et al, N Engl J Med. 2001;344:233-4; Yang et al, Am J Med Sci. 2010;339:190-1). PMID- 21030853 TI - Resolution of anuric acute kidney injury after left renal angioplasty and stenting for a totally occlusive in-stent restenosis of a solitary kidney. AB - The authors report a case of unilateral renal artery in-stent occlusion leading to anuric acute kidney injury in a patient with solitary functional kidney. To their knowledge, this is the first reported case of anuric acute kidney injury, which was successfully treated with percutaneous stenting leading to return of renal function to baseline and a prompt resolution of anuria. This case demonstrates that percutaneous revascularization is a safe and feasible treatment option for in-stent occlusion of renal artery supplying a solitary functional kidney and underscores the importance of early recognition and treatment. PMID- 21030856 TI - Transbrachial intra-aortic balloon pumping for high-risk percutaneous coronary intervention. AB - The beneficial effect of placement of intra-aortic balloon (IAB) pump before revascularization in patients with high-risk coronary anatomy and impaired left ventricular systolic function is documented. However, the conventional insertion of IAB pump via the common femoral artery may be contraindicated or may be even impossible in patients with severe vascular disease. Recently, the percutaneous insertion of IAB via the brachial artery has been shown to be effective and safe in small series of patients with vascular disease undergoing coronary artery bypass surgery. The authors report their experience with a patient with aortobifemoral bypass grafts who underwent successful stenting of a trifurcating distal left main stenosis after placement of a 7.5-Fr IAB pump via the left brachial artery. PMID- 21030858 TI - Evaluation of 18F-FDG PET/CT in early-stage cervical carcinoma. AB - INTRODUCTION: The purpose is to evaluate 18F-fluorodeoxy glucose-positron emission tomography (PET)/computed tomography (CT) for the detection of cervical carcinoma of the International Federation of Gynecology and Obstetrics stages Ib and IIa. METHODS: Twenty-two patients with cervical carcinoma were included in this study. Eleven of them were at the International Federation of Gynecology and Obstetrics stage Ib, and the remaining patients were at stage IIa. All the patients underwent 18F-fluorodeoxy glucose-PET/CT scan, and in 15 patients, additional delayed imaging of pelvis was performed. The PET/CT findings were compared with histopathologic and follow-up results. RESULTS: Of the 22 patients, 20 had cervical cancer with abnormal uptake that were detected directly using PET/CT without additional information from delayed imaging of pelvis; the other 2 patients showed lesions with no abnormal uptake. The use of delayed imaging of the pelvis with PET/CT corrected 1 false-negative case. Thus, the accuracy of PET/CT for early-stage cervical carcinoma was 95.45% (21/22). The uptake of early stage cervical carcinoma showed no statistical significance between the group of stage Ib and the group of stage IIa (P > 0.05). The false-negative rate and negative predictive value of PET/CT imaging in predicting pelvic nodal involvement were 6.25% (1/16) and 93.75%, respectively. CONCLUSIONS: PET/CT showed a high accuracy for the diagnosis of early-stage cervical cancer and a high-negative predictive value for predicting the pelvic nodal status in early stage cervical cancer. PMID- 21030857 TI - Candida glabrata spinal osteomyelitis. AB - Invasive disease caused by Candida spp. is being appreciated with increased frequency especially associated with widespread use of immunosuppressive drug therapy. We report a case of spinal osteomyelitis and epidural abscess caused by Candida glabrata occurring in a patient who had been diagnosed with candidemia 3 months before that patient was treated with fluconazole. The infection was successfully treated with amphotericin B, but the patient eventually required surgical intervention for spondylolisthesis with impingement on the cauda equina. PMID- 21030859 TI - Galectin-3 is overexpressed in various forms of endometriosis. AB - Endometriosis is an enigmatic disease of unknown etiology and pathogenesis, which is defined as the presence of endometrial glands and stroma outside the uterus. The most widely accepted theory to explain endometriosis is probably the transplantation of an endometrial fragment during menstruation to ectopic sites, but the development of endometriosis is extremely complex and includes the adherence to the peritoneal surface and secondary invasion of the underlying tissues. In this study, we have investigated the potential role of galectin-3 (gal-3), a member of a group of carbohydrate-binding proteins, which plays a major role in cell adhesion, migration, angiogenesis, and invasion. The expression of gal-3 has been carried out by immunohistochemistry, according to the different phases of cycle in 50 cases of endometriosis (peritoneal endometriosis: n=10; ovarian endometriosis: n=10; deeply infiltrating endometriosis: n=30) and in 34 cases of eutopic endometrium (10 without endometriosis and 24 with endometriosis). In the proliferative and secretory phases of the cycle, the nuclear and membranous gal-3 expression was higher, first in each variant of the endometriosis than in the eutopic endometrium (P<0.05), and second in the eutopic endometrium of women with endometriosis than in eutopic endometrium of women without endometriosis. Our data suggest that gal 3 may have a potential role in the development of endometriosis. PMID- 21030860 TI - Immunohistochemical and molecular markers in breast phyllodes tumors. AB - Phyllodes tumors of the breast are diagnostically and managerially enigmatic, as their malignant potential is difficult to predict based on the standard morphologic criteria. Thus, there is a need for additional markers of biologic potential. Although a number of ancillary tests have been reported, consensus in the literature is lacking. We studied 38 cellular fibroadenomas and phyllodes tumors of various grade (World Health Organization benign, borderline, and malignant) with a panel of immunohistochemical stains (p53, CD117, phospho Histone3, mdm2, cdk4) and screened 26 of the tumors for mutations across 30 cancer-related genes using PCR and mass-spectrometry based methods. p53 and phospho-Histone3 (mitotic marker) showed increased staining in higher grade phyllodes tumors. CD117, mdm2, and cdk4 showed no difference in expression across different grades of phyllodes tumors. Mutational analysis revealed an S8R substitution in FBX4 (an E3 ubiquitin ligase) in 3 cases: 1 benign and 2 borderline. The S8R substitution seems to be more common in phyllodes tumors (11.5%) as compared with other cancers. FBX4 S8R cases had high cyclin D1 expression, but this finding was not specific. Our data support earlier studies showing that p53 has potential use in pathologic assessment of phyllodes tumors, and we newly characterized phospho-Histone3 for this application. Further studies are needed to characterize the molecular pathogenesis of the phyllodes tumors, as we were unable to identify activating mutations despite screening for a large panel of activating hotspot mutations. The significance of the FBX4 substitution deserves further investigation. PMID- 21030862 TI - Automated ERCC1 immunohistochemistry in non-small cell lung cancer: comparison of anti-ERCC1 antibodies 8F1, D-10, and FL-297. AB - INTRODUCTION: The excision repair cross-complementation group 1 (ERCC1) protein is the key enzyme of the nucleotide excision repair (NER) pathway and thus a potential predictor for platinum-based chemotherapy response. We aimed for evaluating different anti-ERCC1 antibodies on formalin-fixed tumor tissue of non small cell lung cancer patients by automated immunohistochemistry (IHC). METHODS: ERCC1 protein expression was assessed on a tissue microarray of 491 NSCLC's using 2 monoclonal mouse (Mab 8F1, Mab D-10) and 1 polyclonal rabbit (Rab FL-297) antibody. Two automated IHC platforms with different detection systems and immunofluorescence were used. Protein expression levels were independently scored by 2 pathologists for both intensity and intensity multiplied by percentage of positive cells (H-score). RESULTS: On both platforms, the 8F1 ab showed best nuclear staining quality. D-10 had additional unspecific background at the plasma membrane and in goblet cells. FL-297 could not be scored owing to high cytoplasmic background. Both 8F1 and D-10 antibodies produced a speckled granular pattern over the whole nuclear compartment. No intranuclear compartmentalization was observed, apart from omission of the nucleolus. Interobserver kappa value was good to very good for 8F1 and D-10. Using 8F1, low ERCC1 was correlated with the adenocarcinoma histotype, increased tumor size and clinical stage, high pT and pN category and the presence of metastasis. No relation to progression-free or overall survival was observed. CONCLUSIONS: In terms of staining quality and restriction to the nuclear compartment, the antibody 8F1 is superior to D-10 or FL-297 on automated IHC platforms. PMID- 21030861 TI - Neuroendocrine markers expression in pancreatic serous cystadenoma. AB - BACKGROUND: The histologic diagnosis of pancreatic serous cystadenoma (SCA) is straightforward in most surgically resected specimens. However, in small biopsies, diagnosis could be challenging. Given the increased use of immunohistochemistry, we sought to investigate the expression of neuroendocrine markers in this entity and compare it with pancreatic neuroendocrine tumors (NETs). MATERIALS AND METHODS: Eighteen NET and 12 SCA cases were collected from our files. The cases were stained with CD56, synaptophysin, and chromogranin A. The percentage of positive cells was recorded. A percentage greater than 10 was considered as the cutoff. Fisher exact test was used for statistical analysis. RESULTS: For SCA, CD56, synaptophysin, and chromogranin A were expressed in 75%, 92%, and 0% of the cases, respectively, whereas in NET they were expressed in 89%, 100%, and 83%, respectively. Therefore, only chromogranin A could differentiate between these 2 entities based on immunohistochemistry (P=0.003). The entrapped Langerhans islets in the walls of microcysts could be a pitfall. CONCLUSIONS: Our data indicate that a significant proportion of SCA shows positive immunoreaction to CD56 and synaptophysin. Therefore, these markers should be interpreted with caution, particularly in a problematic small biopsy setting. PMID- 21030865 TI - Small birth size, adult overweight, and risk of acute myocardial infraction. AB - BACKGROUND: The association between small size at birth and increased risk of cardiovascular disease in adulthood is well established. This relationship is commonly interpreted according to the "thrifty phenotype hypothesis," which states that the association is generated by a mismatch between fetal and postnatal nutrition. Empirical support for an interaction between impaired fetal growth and later overnutrition is, however, sparse and partly conflicting. METHODS: The Stockholm Heart Epidemiology Program is a population-based case control study of risk factors for acute myocardial infarction (MI); data were available for 1058 cases and 1478 controls. Using logistic regression, we studied the effect of size at birth, and its interactive effect with body mass index (BMI), at 3 occasions in adulthood, on the risk of MI. Biologic interaction was estimated with the synergy index. RESULTS: Very low birth weight for gestational age was associated with increased risk of MI (odds ratio [OR] = 2.0; 95% confidence interval [CI] = 1.4-2.9; attributable fraction = 5%). In nonfatal cases, adjustment for waist-hip ratio, insulin resistance, blood pressure, and lipids reduced the point estimate somewhat. Low birth weight for gestational age in combination with high BMI at the time of the MI produced an OR of 10.8 (3.6 31.8) for MI compared with normal birth weight and normal BMI; the synergy index was 6.5 (95% CI = 1.8-24.0). CONCLUSIONS: The synergism between small size at birth and high adult BMI supports the thrifty phenotype hypothesis. However, this mechanism seems to pertain to only a small fraction of the acute MI cases, implying minor public health importance. PMID- 21030864 TI - Parkinson disease and malignant melanoma in first-degree relatives of patients with early-onset melanoma. AB - BACKGROUND: In a recent study, the link between Parkinson disease and malignant melanoma in patients was also observed in nuclear families, suggesting a possible genetic link between the 2 diseases. METHODS: To clarify the strength of the association, we used the nationwide Danish cancer and population registers to identify 8567 parents and 7310 siblings of patients in whom malignant melanoma was diagnosed at age 50 years or less. Hospital register data were used to follow relatives for a primary diagnosis of Parkinson disease between 1977 and 2008, and to calculate hospitalization rates for Parkinson disease in the general Danish population for comparison. Similarly, cancer registry data were used to trace cases of malignant melanoma. RESULTS: The hospitalization rate ratio for Parkinson disease among the melanoma cohort was slightly increased (ratio of observed to expected hospitalizations = 1.2 [95% confidence interval = 0.9-1.5]) on the basis of 54 observed cases. In contrast, the risk among relatives for malignant melanoma was markedly increased. There was no overlap between families affected by multiple cases of Parkinson disease and those affected by multiple cases of malignant melanoma. CONCLUSIONS: For the age range investigated, our data do not support a genetic link between Parkinson disease and malignant melanoma. PMID- 21030863 TI - Immunophenotype of nipple adenoma in a male patient. AB - BACKGROUND: Adenoma of the nipple is rare in men. It must be distinguished from a breast carcinoma and from Paget disease. In this sense, immunohistochemistry can be of some help. In women, for instance, immunoexpression of c-erbB-2 favors a diagnosis of Paget disease, according to some studies. Nevertheless, we have not found any studies on HER2/neu status, estrogen receptors, or progesterone receptors in nipple adenoma of male patients. METHODS: We present a case of an adenoma of the nipple in a 21-year-old man in which we carried out a wide immunohistochemical study. RESULTS: The lesion did not express estrogen receptors, progesterone receptors, or androgen receptors. The HercepTest was negative. Smooth muscle Actin and p63 were remarked in the basal layer of the tumoral tubules, supporting the benignancy of the lesion. CONCLUSIONS: This case of adenoma of the nipple in a male shows an immunophenotype that is similar to the ones reported in female patients. PMID- 21030866 TI - Residential air pollution and otitis media during the first two years of life. AB - BACKGROUND: : Otitis media is the leading reason young children receive antibiotics or visit a physician. We evaluated the impact of ambient air pollution on outpatient physician visits for otitis media in a population-based birth cohort. METHODS: : All children born in southwestern British Columbia during 1999-2000 were followed until the age of 2 years. Residential air pollution exposures were estimated for the first 24 months of life by inverse distance weighting of monitor data (CO, NO, NO2, O3, PM2.5, PM10, SO2), temporally adjusted land-use regression models (NO, NO2, PM2.5, black carbon, woodsmoke), and proximity to roads and point sources. We used generalized estimating equations to longitudinally assess the relationship between physician visits for otitis media (ICD-9) and average pollutant exposure in the 2 months prior to the visit, after adjustment for covariates. RESULTS: : Complete exposure and risk-factor data were available for 45,513 children (76% of all births). A total of 42% of subjects had 1 or more physician visits for otitis media during follow-up. Adjusted estimates for NO, PM2.5, and woodsmoke were consistently elevated (eg, relative risk of 1.10 [95% confidence interval = 1.07-1.12] per interquartile range [IQR] increase in NO; 1.32 [1.27-1.36] per IQR increase in days of woodsmoke exposure). No increased risks were observed for the remaining pollutants (eg, 1.00 [0.98-1.03] per IQR increase in PM10; 0.99 [0.97-1.01] per IQR increase in black carbon). CONCLUSIONS: : Modest but consistent associations were found between some measures of air pollution and otitis media in a large birth cohort exposed to relatively low levels of ambient air pollution. PMID- 21030868 TI - The inability to visualize the ampulla of Vater is an inherent limitation of capsule endoscopy. AB - OBJECTIVE: Lesions missed by capsule endoscopy (CE) have been reported and this may be partly because of the properties of the capsule. We aimed to compare the ability of Pillcam SB1, SB2, ESO1 and ESO2 to identify the ampulla of Vater (AoV). METHODS: Patients were divided into four groups: SB1 [single head capsule, 2 frames per second (fps), a 140 degrees field of view, n=50], SB2 (single head, 2 fps, a wider field of view of 156 degrees , n=50), ESO1 (double head, 14 fps, a 140 degrees field of view, n=8) and ESO2 (double head, 18 fps, an extra wide field of view of 169 degrees , n=12). Metoclopramide was administered in 25 out of 50 patients in SB1 group and all patients in SB2 group before CE. RESULTS: The AoV was not detected in any patients having SB1, irrespective of the use of metoclopramide. The AoV was identified in only nine out of 50 (18%) patients in the SB2 group confirming the benefit of a widened field of view, however, showed that even this capsule failed to visualize the AoV in more than three-quarters of cases. Double-headed capsules with faster frame rates did not improve the detection rate, the AoV was visualized in only one out of 12 (8%) patients in the ESO2 group but none in the ESO1 studies. CONCLUSION: Currently, CE is not reliable to visualize the AoV and by inference the proximal duodenum. This is most likely related to the speed at which the capsule passes through the fixed second part of the duodenum. Faster frame rates plus a wider field of view do not overcome this limitation, which could account for missed lesions elsewhere in the small bowel. PMID- 21030867 TI - Tobacco dependence and awareness of health risks of smoking in patients with inflammatory bowel disease. AB - BACKGROUND AND AIM: Smoking is a risk factor for developing Crohn's disease (CD) and worsens its outcome. Conversely, in ulcerative colitis (UC), the onset may be triggered by the smoking cessation and smoking may be beneficial. To help to ascertain whether patients with inflammatory bowel disease (IBD) would benefit from attending a smoking cessation clinic, we assessed: first, the prevalence of smoking; second, patients' awareness of the effects of smoking, and finally nicotine dependence in IBD patients compared with the healthy and disease-matched controls. METHODS: A total of 246 consecutive IBD outpatients (173 patients with CD, 73 patients with UC) completed a questionnaire on smoking habits and its effect on IBD. Smokers were assessed for dependence using the Fagerstrom test for nicotine dependence (FTND) score and their results were compared with those of age, sex, and ethnicity-matched healthy (five controls for each IBD patient) and asthma controls (one control for each IBD patient) attending a smoking cessation clinic. RESULTS: Thirty five out of 173 patients (20%) with CD and nine out of 73 patients (12%) with UC were current smokers, with 52 out of 173 patients (30%) with CD and 28 out of 73 patients (38%) with UC being ex-smokers. Ninety out of 173 patients (52%) with CD knew that smoking worsens CD, whereas only 15 out of 73 patients (21%) with UC knew of the beneficial effects of smoking on their disease (P=0.032). Knowledge was unrelated to smoking status. In patients with CD, the median (range) FTND score was 3 (0-8) compared with 7 (2-10) in healthy (P<0.001) and 6 (2-9) in asthma controls (P<0.0001). Only seven of the 35 (20%) smoking patients with CD were highly dependent (FTND score >=6). Similarly, in the patients with UC, the FTND score was 1 (0-4), lower than in healthy, [6 (2 10)], and asthma controls, [7 (4-10); (P<0.004 for both groups)]. CONCLUSION: Patients with CD were better informed about the effects of smoking on their own disease than the patients with UC. Nicotine dependence in IBD patients is lower than in smokers' clinic clients and comparable with that of the general population. Their low nicotine dependence suggests that most IBD patients could be weaned off the smoking habit successfully in the IBD clinic and referral to a smoking cessation clinic was offered to the highly dependent minority and others expressing interest in attending. PMID- 21030869 TI - Fecal calprotectin concentrations in alcoholic patients: a longitudinal study. AB - OBJECTIVES: Excessive alcohol consumption often results in intestinal damage, mediated by inflammatory processes, mainly characterized by an increased influx of leukocytes. Fecal calprotectin is a granulocyte cytosolic protein, representing as a promising marker of subclinical intestinal inflammation. In this study, we assessed fecal calprotectin concentrations (FCCs) in current drinking alcoholics, both at the baseline, and then during a subsequent 84-day period. Moreover, FCCs in the alcoholics were compared with the FCCs in healthy controls. METHODS: Twenty-eight, active-drinking alcoholics were enrolled in this study and compared with 40 healthy volunteers as the control group. In alcoholics, FCCs were determined at the beginning of the study (baseline; T0) and then every 2 weeks (T1-T6) during the following 84-day period. Potential differences in FCCs were analyzed between alcoholics and healthy controls, and during the 84-day period within the group of alcoholics. In addition, an analysis of FCCs was conducted in three subgroups of alcoholics, considering their drinking status during the 84-day period (abstinent, relapsed, and active). RESULTS: At baseline, no significant differences in median FCCs were found between alcoholics and controls. No significant changes of median FCCs were found, comparing baseline FCCs and FCCs during the 84-day period (T1-T6) in the whole group of alcoholics, nor in the three subgroups of alcoholics. CONCLUSION: FCCs in active-drinking alcoholics are not significantly different, compared with the healthy controls. Moreover, FCCs do not significantly differ according to the alcohol drinking status. These results may suggest the absence of a subclinal intestinal inflammation involving neutrophils in the alcoholics. PMID- 21030870 TI - Use of mood stabilizers for hospitalized psychotic and bipolar disorder patients. AB - Treatments given to patients with primary psychotic disorders include mood stabilizers (MSs) combined with other psychotropics, despite the limited evidence of efficacy, safety, and lack of regulatory approval. We analyzed records of 636 inpatients at the McLean Hospital (2002-2009), who were diagnosed with bipolar disorder (n=318), a schizoaffective disorder (n=210), or schizophrenia (n=108), to evaluate MS-usage, drug-selections, combinations and doses, improvement, adverse-effect risks, associated factors, and secular trends. Between 2002 and 2009, the use of MSs increased from 53 to 94% of patients, MSs per patient increased by 74%, and the total final doses (lithium-equivalents in milligrams/day) increased by 35%. The most commonly prescribed MSs ranked: valproate, lithium, lamtogrine. With the use of MSs, the duration of hospitalization was longer by an average of 18%, Clinical Global Impression ratings improved by 55%, and adverse-effects risk was lower by 22%. In multivariate logistic modeling, treatment with a MS was associated with: (i) most recent year of sampling, (ii) more psychotropics per patient at discharge, (iii) diagnosis (schizophrenia < schizoaffective or bipolar disorders), (iv) longer period of hospitalization, and (v) somewhat younger age. MSs, usually in combination with antipsychotics, were used increasingly for inpatients over the past decade, including for patients with primary psychotic disorders. The effectiveness and safety of this practice remain to be evaluated adequately. PMID- 21030871 TI - Colonoscopic findings and histologic diagnostic yield of colorectal endometriosis. AB - BACKGROUND: No study has systematically investigated the colonoscopic findings and histologic diagnostic yield in the diagnosis of colorectal endometriosis. OBJECTIVES: We classified the colonoscopic features of colorectal endometriosis and determined the diagnostic yield of endoscopic biopsy in relation to endoscopic subtypes of colorectal endometriosis. METHODS: A total of 17 patients with colorectal endometriosis were assessed. The data from the colonoscopic and histologic assessments made between November 1994 and October 2009 were retrospectively analyzed in single tertiary referral teaching hospital. RESULTS: Colonoscopy showed eccentric wall thickening in 14 patients (82%) and polypoid lesions in 3 patients (18%). Surface nodularities were noted in 11 of the 14 patients (79%) with eccentric wall thickening, and in 1 of the 3 patients (33%) with polypoid lesions. The overall histologic diagnostic yield was 47% (8 of the 17 patients). The rate of histologic confirmation was higher in patients with surface nodularities (8 of the 12 patients, 67%) versus those without (0 of the 5 patients, 0%) surface nodularities (P=0.02). CONCLUSIONS: Eccentric wall thickening is the most common colonoscopic finding of colorectal endometriosis, and the histologic diagnostic yield of endoscopic biopsy is high when lesions are accompanied by surface nodularities. PMID- 21030872 TI - Endosopic autofluorescence imaging is useful for the differential diagnosis of intestinal lymphomas resembling lymphoid hyperplasia. AB - BACKGROUND: A method for the differential diagnosis of intestinal lymphomas resembling lymphoid hyperplasia (LH) by endoscopy remains to be clearly established. OBJECTIVE: To evaluate the usefulness of autofluorescence imaging (AFI) in diagnosing intestinal lymphoma. SETTING: Single-center study. DESIGN: Prospective study. PATIENTS: One hundred forty-three samples obtained from the intestinal tissues of 21 patients with malignant lymphoma were included in the study. INTERVENTIONS: The terminal ileum and entire colon were observed using conventional endoscopy equipped with AFI. The AFI images were taken by 3 endoscopists and then were evaluated by 3 predominant color intensities; green, magenta, and blended. To quantify the strength of fluorescence captured by AFI, the area of the obtained biopsy specimens on images was manually traced, the signal density of either magenta or green was measured, and then the ratio of the reverse gamma value of green divided by that of magenta was defined as the Fluorescence index (F index). MAIN OUTCOME MEASUREMENTS: The ability to use AFI to distinguish intestinal lymphoma from normal or LH. RESULTS: The cell density is inversely proportional to the F index. The F index of lymphoma was significantly lower than that of normal mucosa or LH. The visual classification of AFI showed the overall accuracy in diagnosing lymphoma was 91.5%, and was well correlated with the F index. LIMITATIONS: Single-center study. CONCLUSIONS: AFI embossed lymphoma lesions seemed as magenta and could be discriminated from LH or normal mucosa with a high overall accuracy through perception of the cell density of the lesion. Therefore, AFI is considered to be an effective procedure for determining the accurate stage and appropriate therapy in intestinal lymphoma. PMID- 21030873 TI - Mind the gaps: confocal endomicroscopy showed increased density of small bowel epithelial gaps in inflammatory bowel disease. AB - OBJECTIVES: Confocal endomicroscopy can be used to image intestinal mucosa. Epithelial gaps resulting from shedding of epithelial cells have been reported in patients. We hypothesize that the rate of epithelial cell shedding increases in patients with Crohn's disease, leading to more epithelial gaps and barrier dysfunction. In this study, we used probe-based confocal laser endomicroscopy to quantify epithelial cells and gaps in patients with Crohn's disease compared with controls. We also determined the density of epithelial gaps in a mouse model of inflammatory bowel disease-interleukin-10-deficient (IL-10) mice, versus the background strain using rigid probe confocal endomicroscopy. METHODS: Probe-based confocal laser endomicroscopy of the terminal ileum of both patients with Crohn's disease and controls was performed by a single endoscopist during colonoscopy. In mice, sections of the small intestine were imaged using a rigid confocal probe. Gap density was defined as the number of epithelial gaps per 1000 cells counted. RESULTS: In this study, we examined 6 controls (2 male and 4 female; median age 59 y) and 8 patients with Crohn's disease (5 male and 3 female; median age 42 y). The mean gap densities (+/-standard error) observed for the 2 groups were 17.7+/ 5.6 and 117+/-33 gaps per 1000 cells, respectively (P<0.01). For control and IL 10 mice, the gap densities were 10.5+/-2.2 and 17.8+/-1.4 gaps per 1000 cells, respectively (P<0.01). CONCLUSIONS: The epithelial gap density was significantly higher in patients with Crohn's disease than controls. Gap density was also elevated in the mouse model of inflammatory bowel disease. PMID- 21030874 TI - Effect of a patient navigator program on the volume and quality of colonoscopy. AB - BACKGROUND AND GOALS: To increase colorectal cancer screening among urban minorities, New York Presbyterian Hospital/Columbia University, with support from the New York City Department of Health and the Citywide Colon Cancer Control Coalition (C5), instituted a patient navigation and direct endoscopic referral system. We assessed the effect of this program on the volume of colonoscopy in this institution, which caters to a socioeconomically diverse patient population. STUDY: We compared colonoscopy volume during the first year of the navigator program with the volume during the year before this program. We stratified on Medicaid status to assess the secular trend of screening rates. To assess quality during this period, we measured cecal intubation rates, preparation quality, and adenoma detection rates. RESULTS: Of the 749 patients assessed by the patient navigators, 678 (91%) underwent colonoscopy. Colonoscopy volume among the Medicaid outpatients increased by 56% (957 to 1489). Adenoma detection was 27% and the cecal intubation rate was 97%. Comparing navigated patients with the nonnavigated Medicaid outpatients, preparation quality was superior (34% vs. 40% suboptimal, P=0.0282), although preparation quality remained inferior to that of private patients (20% suboptimal, P<0.0001). CONCLUSIONS: Volume of the colonoscopy increased, coinciding with the onset of the patient navigation program. This increase was nearly entirely owing to a rise in the colonoscopies among Medicaid outpatients, the principal focus of the navigator program. This increase in quantity was accomplished while maintaining an overall high level of quality as measured by cecal intubation rates and adenoma detection, although preparation quality requires further efforts at improvement. PMID- 21030875 TI - Clinical utility of the wireless pH capsule. AB - GOAL: The aim of this prospective study was to determine whether this test changes patient diagnosis, provides new information, or alters patient care. BACKGROUND: The wireless pH capsule is widely used to evaluate symptoms of acid reflux, although the clinical utility of this test is unknown. STUDY: Before pH capsule placement, referring providers completed a questionnaire requesting indications for the test, symptoms, prior testing, and medication use. A follow up survey determined whether providers believed that results of the wireless pH test provided new information, changed patient diagnosis or altered patient management. RESULTS: During a 14-month period, 598 wireless pH capsule studies were conducted; 490 patients were eligible for inclusion, and 309 questionnaires were returned (63%). Mean patient age=48 (+/-15 y). The most common symptom leading to pH capsule placement was acid reflux (heartburn/regurgitation; 62%), followed by chest pain (11%). Wireless pH capsule results provided new information in 88% of patients, changed the diagnosis in 22%, and altered management in 63%. CONCLUSIONS: This study shows the clinical utility of the wireless pH capsule, with test results frequently providing new information, altering patient management or changing patient diagnoses. Future studies should define specific test characteristics most likely to influence patient care. PMID- 21030876 TI - Recommendations for the use of intraosseous vascular access for emergent and nonemergent situations in various health care settings: a consensus paper. PMID- 21030877 TI - "Getting from here to there"--mechanisms and limitations to the activation of the androgen receptor in castration-resistant prostate cancer. AB - Despite the clinical regression that typifies the initial response of advanced prostate cancer to gonadal testosterone depletion, tumors eventually progress. However, evidence supports the concept that signaling via the androgen receptor (AR) is important in progression to castration-resistant prostate cancer (CRPC).Steroid hormones are synthesized from cholesterol in a series of tightly regulated steps involving the cleavage of carbon-carbon bonds, the introduction of functional groups derived from activated molecular oxygen, and the oxidation and reduction of carbon-carbon and carbon-oxygen bonds. In the adrenal cortex and gonads, steroidogenesis is tightly regulated, very efficient, and highly directional. In contrast, steroid metabolism in peripheral tissues is characterized by competing enzymes and pathways, low efficiency, and great variability. Many steps are mechanistically and functionally irreversible, but some are not, and the repertoire of specific enzymes, intracellular redox state, and access to hormone precursors all contribute to steroid flux and accumulation.The investigation of steroid metabolizing enzymes in CRPC often assumes that the pathways and the patterns of metabolism mirror those defined in the adrenals and the gonads and validated by human deficiency syndromes. Unfortunately, several potential pathways using different enzymes might contribute substantially to androgen synthesis in CRPC. Finally, a number of mechanisms have been reported by which the AR is activated independent of ligand. Recent observations have suggested that AR forms with constitutive activity occur in CRPC, stimulating transcription without a requirement for ligand. This overview outlines a broad view of how the mechanisms by which the AR may be activated, whether by alternate pathways of androgen synthesis or the production of alternate forms of the AR, with an emphasis on what aspects must be accounted for when using model systems to explore the biology of human prostate cancer. PMID- 21030878 TI - MicroRNA-155 silencing enhances inflammatory response and lipid uptake in oxidized low-density lipoprotein-stimulated human THP-1 macrophages. AB - It has been proposed that the inflammatory response of monocytes/macrophages induced by oxidized low-density lipoprotein (oxLDL) is a key event in the pathogenesis of atherosclerosis. MicroRNA-155 (miR-155) is an important regulator of the immune system and has been shown to be involved in acute inflammatory response. However, the function of miR-155 in oxLDL-stimulated inflammation and atherosclerosis remains unclear. Here, we show that the exposure of human THP-1 macrophages to oxLDL led to a marked up-regulation of miR-155 in a dose-dependent manner. Silencing of endogenous miR-155 in THP-1 cells using locked nucleic acid modified antisense oligonucleotides significantly enhanced oxLDL-induced lipid uptake, up-regulated the expression of scavenger receptors (lectinlike oxidized LDL receptor-1, cluster of differentiation 36 [CD36], and CD68), and promoted the release of several cytokines including interleukin (IL)-6, -8, and tumor necrosis factor alpha (TNF-alpha). Luciferase reporter assay showed that targeting miR-155 promoted nuclear factor-kappa B (NF-kappaB) nuclear translocation and potentiated the NF-kappaB-driven transcription activity. Moreover, miR-155 knockdown resulted in a marked increase in the protein amount of myeloid differentiation primary response gene 88 (MyD88), an important adapter protein used by Toll-like receptors to activate the NF-kappaB pathway. Our data demonstrate that miR-155 serves as a negative feedback regulator in oxLDL-stimulated THP-1 inflammatory responses and lipid uptake and thus might have potential therapeutic implications in atherosclerosis. PMID- 21030879 TI - Effective antihypertensive strategies for high-risk patients with diabetic nephropathy. AB - AIM: Clinical guidelines recommend blood pressure (BP) lowering and renin angiotensin-aldosterone system inhibition to slow kidney disease progression in patients with diabetic nephropathy. This study's purpose was to determine whether an antihypertensive regimen including a maximally dosed angiotensin-converting enzyme inhibitor could safely achieve target BP in indigent, predominantly minority patients with this disease. METHODS: We studied 81 hypertensive adults (52% Hispanic and 31% African American) with nephropathy attributed to type 1 or 2 diabetes during the run-in period of a randomized controlled trial. The subjects received lisinopril titrated to 80 mg daily and additional antihypertensives to target a systolic BP (SBP) lower than 130 mm Hg. Blood pressure and serum potassium level were measured weekly, and a 4-gram sodium diet was prescribed. The primary outcome variable was SBP change from screening to randomization. Success in achieving SBP goal, change in urine albumin-creatinine ratio, hyperkalemia (serum potassium >=5.5 mmol/L) and hypotension (SBP < 100 mm Hg) were also analyzed. RESULTS: The median SBP decreased from 144 to 133 mm Hg (median change, -9.6%.) Fifty-eight (71%) achieved goal SBP during run-in. The median UACR decreased from 206.8 to 112.7 mg/mmol (median change, -42.7%). The UACR reduction correlated with SBP reduction. Seventeen subjects experienced hyperkalemia responsive to dietary/medical management. Two subjects experienced hypotension responsive to medication adjustments. CONCLUSION: A regimen using a maximally dosed angiotensin-converting enzyme inhibitor is safe and effective for achieving BP goal in high-risk, predominantly minority patients with diabetic nephropathy. Implementing this regimen necessitates close monitoring of serum potassium level. PMID- 21030880 TI - The feasibility of plerixafor as a second-line stem cell mobilizing agent in children. AB - In patients heavily pretreated with myelosuppressive chemotherapy or irradiation, Granulocyte colony stimulating factor (G-CSF) may fail to mobilize stem cells from the bone marrow. Plerixafor is emerging as a reliable alternate option in such situations in adult patients. Robust data in support of the high efficacy and safety of plerixafor are available in adults. Very little evidence is available on the usefulness of this drug among children. We report our experience with plerixafor usage on 5 occasions in pediatric patients, with a success rate of 60%. No significant side effects were encountered in any patient. PMID- 21030881 TI - Unilateral foot abduction orthosis: is it a substitute for Denis Browne boots following Ponseti technique? AB - The use of foot abduction orthosis [Denis Browne boot (DBB)] is vital for maintaining correction after the Ponseti technique for treating idiopathic clubfoot. Lack of adherence to DBB regimen is reported to be a potent cause for recurrence. Adherence to the boots and bars programme is difficult and patients sometimes resist their use. The evaluation of alternatives that may facilitate adherence is therefore necessary and reasonable. There are less data published regarding the outcome after the use of alternative splints. In patients who showed poor adherence to DBB, we introduced a novel unilateral foot abduction orthosis (UFAO) as an alternative. The aim of this study was to determine whether the recurrence rates were increased by exchanging DBB with UFAO in nonadherent patients and to find out whether UFAO was more acceptable to families who had refused to use DBB. We reviewed 27 children with 35 idiopathic clubfeet. Twenty three patients used the boots and bars programme for the first 3 months after completion of serial casting, before UFAO was introduced into the treatment plan for resistance to DBB usage. In four cases, UFAO was commenced immediately after the serial casting. The mean follow-up was 25 months (16-36 months). Most families reported that UFAO was easier for their child to use and facilitated adherence was observed. Recurrence (the need for further casting or operation) was observed in 11 feet. Six of these 11 recurrences responded favourably to a further period of serial casting with or without repeated tendoachilles tenotomy. Three of these 11 patients responded favourably to tibialis anterior transfer and two required a traditional posteromedial release. The recurrence rates in patients using UFAO were higher compared with those reported by others using DBB after Ponseti serial casting. Our results indicated that although a unilateral orthosis is preferred and accepted by families who do not adhere to a DBB regimen, recurrence with UFAO use is higher. This study therefore questions the effectiveness of UFAO as an alternative to DBB. The importance of following the original method described by Ponseti should be stressed. PMID- 21030883 TI - The effects of 20-hydroxyecdysone and 17beta-estradiol on the skin of ovariectomized rats. AB - OBJECTIVE: 20-hydroxyecdysone has numerous favorable effects on a variety of organs, including the skin, where it improves wound healing. It is devoid of estrogenic and androgenic effects. Therefore, application of 20-hydroxyecdysone might be a new approach to improve skin conditions in postmenopausal women, and this was investigated in ovariectomized (OVX) rats. METHODS: After ovariectomy, rats received Ecd (18, 57, or 116 mg/animal/day) or 17beta-estradiol (E2)-3 benzoate (60 MUg/kg body weight) in food for 12 weeks, and skin samples were evaluated histologically to quantify two dermal layers, the subcutaneous fat and muscle layers. RESULTS: Epidermal thickness was lowest in the OVX animals, slightly higher in the E2-treated animals, and significantly higher in the Ecd treated animals. Dermal thickness was lowest in the intact and E2-treated animals and highest in the Ecd-treated animals. The subcutaneous fat layer was thickest in the OVX animals, thinner in the intact animals, and intermediate in the Ecd treated animals. The muscle layer was smallest in the OVX and intact animals and significantly larger in the E2- and Ecd-treated animals. The number of proliferating cell nuclear antigen antibody-positive cells was lowest in OVX controls and significantly higher in all other groups. CONCLUSIONS: The Ecd induced increases in epidermal and dermal thickness are suggestive of functional changes of the skin. The decreased amounts of subcutaneous fat in the E2- and Ecd treated animals point to either a fat catabolic or an antianabolic effect. The ovariectomy-induced decrease in subcutaneous musculature was prevented by Ecd but not by E2. The stimulatory effects of Ecd on epidermal and dermal thickness and the muscle-increasing effects in the skin of OVX rats may indicate functional changes of the skin. PMID- 21030882 TI - Additive melanoma suppression with intralesional phospholipid-conjugated TLR7 agonists and systemic IL-2. AB - There remains a compelling need for the development of treatments for unresectable melanoma. Agents that stimulate the innate immune response could provide advantages for cell-based therapies. However, there are conflicting reports concerning whether toll-like receptor (TLR) signaling controls tumor growth. The objective of this study was to evaluate the effect of intralesional administration of a TLR7 agonist in melanoma therapy. B16cOVA melanoma was implanted to TLR7 mice to evaluate the roles of stromal TLR7 on melanoma growth. To capitalize on the potential deleterious effects of TLR7 stimulation on the tumor growth, we injected melanoma tumor nodules with a newly developed and potent TLR7 agonist. B16 melanoma nodules expanded more rapidly in TLR7-deficient and MyD88 mice compared with TLR9 and wild type mice. Repeated injections with low doses of unconjugated TLR7 agonist were more effective at attenuating nodule size than a single high dose injection. To improve the efficacy we conjugated the agonist to phospholipid or phospholipids-polyethylene glycol, which retained TLR7 specificity. The phospholipid conjugate was indeed more effective in reducing lesion size. Furthermore, intralesional administration of the phospholipid TLR7 agonist conjugate enhanced the antimelanoma effects of systemic treatment with interleukin (IL)-2 and prolonged the survival of mice compared with IL-2 alone. Our study showed that: (1) TLR7/MyD88 signaling in the stroma is involved in melanoma growth; and (2) intralesional administration of a TLR7 agonist reduces the growth of melanoma nodules and enhances the antimelanoma effects of IL-2. PMID- 21030884 TI - Impact of CD4 T cell count on the outcome of planned treatment interruptions in early-treated human immunodeficiency virus-infected children. AB - Early highly active antiretroviral therapy is recommended in all vertically human immunodeficiency virus (HIV)-infected infants. We describe the long-term immunologic outcome after planned treatment interruption (PTI) in 7 children diagnosed and treated during acute HIV infection (age <12 weeks). Children had remained a median of 57 months off treatment, 3 of them indefinitely. The 2 patients with the lowest nadir CD4% reinitiated highly active antiretroviral therapy because of a CD4 cell decline of <20%; 2 children resumed treatment because of clinical progression and parents' wishes. All patients experienced a decrease in CD4% after PTI, which particularly affected the naive subpopulation. The interferon-gamma response against HIV-p24 antigen directly correlated with nadir CD4%. Our results suggest that early treatment in HIV-infected infants increases their potential to safely control viral replication after PTI for long periods. PMID- 21030885 TI - Timing of correct parenteral antibiotic initiation and outcomes from severe bacterial community-acquired pneumonia in children. AB - BACKGROUND: The impact of timing of appropriate antibiotic initiation for critically ill children with severe bacterial community-acquired pneumonia (CAP) is unknown. We hypothesized that longer time to initiation of correct parenteral antibiotic would be associated with longer durations of mechanical ventilation, intensive care unit length of stay, and hospital length of stay. METHODS: We retrospectively reviewed medical records of children admitted to Nationwide Children's Hospital between January 2004 and December 2006 with bacterial CAP treated with mechanical ventilation, excluding those with documented viral infection. Time to correct antibiotic was defined as time from presentation to any emergency department to the initiation of a parenteral antibiotic to which cultured pathogens were susceptible. RESULTS: In all, 45 patients, median age 17 months, were identified. Median time to correct antibiotic was 10.3 hours, with 71% of patients receiving correct empiric therapy. After adjusting for severity of illness, longer time to correct antibiotic was independently associated with longer hospital stay (P = 0.007). For the 23 patients in the cohort for whom pneumonia was the primary diagnosis, longer time to correct antibiotic was independently associated with longer durations of mechanical ventilation (P = 0.01), intensive care unit stay (P = 0.001), and hospital stay (P = 0.006). Delays in antibiotic administration as short as 2 to 4 hours were associated with adverse outcomes in this group. CONCLUSIONS: In our critically ill children with severe bacterial CAP, longer delays in receipt of appropriate empiric antibiotics were independently associated with adverse outcomes. PMID- 21030886 TI - Chinese herbal medicine for chronic neck pain due to cervical degenerative disc disease. AB - STUDY DESIGN: Systematic review. OBJECTIVE: To assess the efficacy of Chinese herbal medicines in treating chronic neck pain with radicular signs or symptoms. SUMMARY OF BACKGROUND DATA: Chronic neck pain with radicular signs or symptoms is a common condition. Many patients use complementary and alternative medicine, including traditional Chinese medicine, to address their symptoms. METHODS: We electronically searched CENTRAL, MEDLINE, EMBASE, CINAHL, and AMED (up to 2009), the Chinese Biomedical Database and related herbal medicine databases in Japan and South Korea (up to 2007). We also contacted content experts and hand searched a number of journals published in China.We included randomized controlled trials with adults with a clinical diagnosis of cervical degenerative disc disease, cervical radiculopathy, or myelopathy supported by appropriate radiologic findings. The interventions were Chinese herbal medicines. The primary outcome was pain relief, measured with a visual analogue scale, numerical scale, or other validated tool. RESULTS: All 4 included studies were in Chinese; 2 of which were unpublished. Effect sizes were not clinically relevant and there was low quality evidence for all outcomes due to study limitations and sparse data (single studies). Two trials (680 participants) found that Compound Qishe Tablets relieved pain better in the short-term than either placebo or Jingfukang; one trial (60 participants) found than an oral herbal formula of Huangqi relieved pain better than Mobicox or Methycobal, and another trial (360 participants) showed that a topical herbal medicine, Compound Extractum Nucis Vomicae, relieved pain better than Diclofenac Diethylamine Emulgel. CONCLUSION: There is low quality evidence that an oral herbal medication, Compound Qishe Tablet, reduced pain more than placebo or Jingfukang and a topical herbal medicine, Compound Extractum Nucis Vomicae, reduced pain more than Diclofenac Diethylamine Emulgel. Further research is very likely to change both the effect size and our confidence in the results. PMID- 21030887 TI - Diastematomyelia and tumor in adults: report of two cases and literature review. AB - STUDY DESIGN: Case report and review of the literature. OBJECTIVE: To report on 2 rare cases of association of diastematomyelia with dysembryogenetic tumors and revision of the literature. SUMMARY OF BACKGROUND DATA: Diastematomyelia is an occult spinal diastrophism pathologically characterized by a clefting of the spinal cord with/without its overlying structures. It is often associated with vertebral bony abnormalities, cutaneous lesions, myelomeningocele, hydrocephalus, hydromyelia, Chiari syndrome or Klippel-Feil syndrome. The association of diastematomyelia with dysembryogenetic spinal tumors in adults is extremely rare. Only 13 cases were detected in a literature review since 1951. We report on our experience with 2 new cases. METHODS: An 87-year-old man and a 38-year-old woman presented to our department with incomplete cauda equina syndrome. Both patients underwent complete preoperative imaging. Complete surgical removal of the tumor was performed. Details of these were compared with the ones encountered in literature. RESULTS: Both patients presented complete recovery in the follow-up. From the review of 15 adults described in literature including the present cases, the age ranged between 11 and 87 proving an open rage of onset of symptoms. CONCLUSION: The results of surgery were unclear in literature. In our experience, radical surgery was feasible and good clinical results were obtained. PMID- 21030888 TI - Multiplex real-time polymerase chain reaction: a practical approach for rapid diagnosis of tuberculous and brucellar vertebral osteomyelitis. AB - STUDY DESIGN: Case-control study for assessing a diagnostic test. OBJECTIVE: The aim of this study was to analyze the diagnostic yield of a multiplex real-time polymerase chain reaction (PCR) assay in the differential diagnosis of tuberculous vertebral osteomyelitis (TVO) and brucellar vertebral osteomyelitis (BVO). SUMMARY OF BACKGROUND DATA: Vertebral osteomyelitis (VO) is one of commonest osteoarticular complications of tuberculosis and brucellosis. However, the very similar clinical, radiologic, and histologic characteristics of these entities mean that diagnosis requires etiological confirmation, but conventional microbiologic methods have important limitations. METHODS: Fifteen vertebral samples from patients with TVO or BVO and 9 from pyogenic and nontuberculous mycobacteria VO were studied by multiplex PCR and conventional microbiologic techniques. To identify Brucella DNA, we used a fragment of 207 bp from the conserved region of the gene coding for an immunogenic membrane protein of 31 kDa of B. abortus (BCSP31) and for Mycobacterium tuberculosis complex, a fragment of 164 bp from the intergenic region SenX3-RegX3. RESULTS: The histopathologic findings were inconclusive in 4 of 14 cases (28.6%) with TVO or BVO and cultures were positive in 11 of 15 cases (73.3%). Multiplex PCR correctly identified 14 of the 15 samples from patients with TVO and BVO and was negative in all the control samples. Thus, the overall sensitivity and specificity of the multiplex PCR were 93.3% and 90%, respectively, with an accuracy of 92% (95% CI, 81.4%-100%). CONCLUSION: These results suggest that multiplex real-time PCR is far more sensitive than conventional cultures, and this, together with its speed, makes this technique a very practical approach for the differential diagnosis between TVO and BVO. PMID- 21030889 TI - Development of the Italian version of the revised Scoliosis Research Society-22 Patient Questionnaire, SRS-22r-I: cross-cultural adaptation, factor analysis, reliability, and validity. AB - STUDY DESIGN: Evaluation of the psychometric properties of a translated and culturally adapted questionnaire. OBJECTIVE: Translating, culturally adapting, and validating the Italian version of the revised Scoliosis Research Society-22 Patient Questionnaire (SRS-22r-I) in order to allow its use with Italian-speaking patients with adolescent idiopathic scoliosis (AIS). SUMMARY OF BACKGROUND DATA: Increasing attention is being given to health-related quality of life measures as a means of adding information about the evaluation of AIS. A translated form of the revised SRS-22 has never been validated in Italian patients with AIS. METHODS: The development of the SRS-22 questionnaire involved its translation and back-translation, a final review by an Expert Committee, and testing of the prefinal version to establish its correspondence to the original English version. Psychometric testing included factor analysis, reliability by internal consistency (Cronbach alpha) and test-retest repeatability (Intraclass Coefficient Correlation), and concurrent validity (Pearson correlation) by comparing the SRS-22r-I domains with the Short-Form Health Survey (SF-36) subscales. RESULTS: It took 4 months to develop a shared version of the SRS-22r I, which proved to be satisfactorily acceptable when administered to 223 subjects with AIS. Factor analysis indicated a 4-factor solution (54% of the explained variance), and the questionnaire had an acceptable level of internal consistency (alpha = 0.77) and a high level of test-retest reliability (intraclass correlation coefficient = 0.957). In terms of concurrent validity, the correlations with the related Short-Form-36 subscales were moderate to good in the case of the Pain and Mental Health domains, and moderate in the case of the Function and Self-Image domains. CONCLUSION: The Italian translation of the SRS 22r has a good factorial structure and psychometric properties, and replicates the results of existing English versions of the questionnaire. Its use for research purposes can therefore be recommended. PMID- 21030890 TI - Revision strategy for posterior extrusion of the CHARITE polyethylene core. AB - STUDY DESIGN: This is a case report of a posterior extrusion of the polyethylene core from a CHARITE arthroplasty. This is the first reported case of posterior dislocation of the polyethylene and the revision strategies used to correct this problem. OBJECTIVE: To report a novel failure mechanism and revision strategy for CHARITE total disc arthroplasty (TDA). SUMMARY OF BACKGROUND DATA: Case report at a Level 1 tertiary care referral center in the northeastern United States. METHODS: This is a case report and review of the literature of a patient who sustained posterior dislocation of the polyethylene core from a CHARITE TDA several months after the index procedure. RESULTS: Core dislocation is a known complication of TDA. However, of the known reported dislocations all have been anterior. This case describes the first known occurrence of posterior core dislocation and the revision strategy for this problem. CONCLUSION: This case report highlights the first known case of a posterior dislocation of a CHARITE core. It is likely that altered biomechanical forces generated over time attributed to device failure. An instrumented posterior fusion with removal of the core is what ultimately led to a stable revision construct. PMID- 21030891 TI - Systematic review of cervical pedicle dimensions and projections. AB - STUDY DESIGN: A systematic review of the published literature was conducted specifically looking at studies reporting linear dimension and angular projection data on the anatomy of the cervical pedicle (C1-C7) via radiography or direct measurement. OBJECTIVE: This study aimed to report a more accurate set of dimension data and identify differences based on race and gender, increasing the sample size by aggregating similar data of prior studies measuring the cervical pedicle in Asian, European/American, male, and female populations. SUMMARY OF BACKGROUND DATA: A wide variation in the reports of the dimensions and projections of the cervical pedicle exist partly due to the uniqueness of this structure as well as the effects of small sample sizes and variable races and genders of sample populations of previous studies. METHODS: An extensive literature search was executed, and identified articles were reviewed. A comprehensive database was constructed for synthesis of the identified studies. Subgroups were determined based on the type of population (race, gender, location of study) and radiographic or direct cadaveric measurement. Descriptive statistics were used to analyze and compare these subgroups including: means, standard deviations, and Student t test with the Bonferroni adjustment. RESULTS: In total, the current study reports on 33 studies with the measurements of 1311 partial and complete cervical spines. At a 95% confidence interval statistically significant differences between races were found only at C3 and C4 levels in the pedicle axis length. Male-to-female significant differences existed only at the pedicle axis length of C5 in the Asian population, while sex differences existed in the outer pedicle width and height of C3, C4, C5, C6, and C7 in the European/American population. CONCLUSION: The current study has found that there is no statistical difference in measuring the cervical pedicle via radiography (CT) or directly. There are more significant differences comparing the cervical pedicles of males and females in the European/American population than exists in the Asian population (specifically in pedicle width and height). There are also significant differences at C3 and C4 cervical pedicle between the Asian and European/American population (specifically in the pedicle axis length and transverse angle). PMID- 21030893 TI - Cauda equina syndrome in ankylosing spondylitis: successful treatment with lumboperitoneal shunting. AB - STUDY DESIGN: Retrospective study. OBJECTIVE: To assess outcomes after lumboperitoneal shunting for CES with dural sac dilation and multiple arachnoid diverticula in patients with long-standing AS. SUMMARY OF BACKGROUND DATA: Cauda equina syndrome (CES) is a rare complication of long-standing ankylosing spondylitis (AS). Neurologic symptoms occur insidiously and have a poor prognosis without effective treatment. METHODS: We retrospectively studied cases seen between 1997 and 2009 at our university-hospital rheumatology department. RESULTS: We identified 9 patients with AS and dural sac dilation (mean age: 64, range: 38-75), of whom 8 experienced CES 29.1 years on average (range: 10-51) after AS onset. Presenting symptoms were urinary abnormalities (n = 4), sensory abnormalities (n = 6), or radicular or low back pain (n = 4). The symptoms worsened progressively, with mild (n = 3) to severe (n = 1) motor deficiency, sphincter dysfunction (urinary [n = 6] and/or anal [n = 4] sphincter), and impotence (n = 3). Magnetic resonance imaging showed dural sac dilation (n = 9), multiple lumbar arachnoid diverticula (n = 6), erosions of the laminae and spinous processes (n = 6), and nerve-root tethering (n = 6) with adhesion to the dura mater and vertebrae (n = 7). Cerebrospinal fluid (CSF) flow study by magnetic resonance imaging was performed in 2 patients and showed communication of the diverticula with the CSF. Lumboperitoneal shunting, performed in 5 patients, was followed by improvements in sensation (n = 4), urinary symptoms (n = 2), anal continence (n = 3), and pain. Full recovery of muscle strength was noted in 3 patients. Improvements persisted after a mean of 49 months (range: 18 96). CONCLUSION: Lumboperitoneal shunting induced substantial improvements in all 5 patients treated with this procedure. This result suggests that AS-related CES may be due to chronic arachnoiditis and dural fibrosis leading to diminished CSF resorption with dural sac dilation and diverticula formation. PMID- 21030892 TI - Transient paraplegia due to accidental intrathecal bupivacaine infiltration following pre-emptive analgesia in a patient with missed sacral dural ectasia. AB - STUDY DESIGN: A case report with review of the literature. OBJECTIVE: To highlight the need for careful magnetic resonance imaging evaluation for the presence of incidental lumbosacral dural anomalies before attempting caudal epidural interventions. SUMMARY OF BACKGROUND DATA: Pre-emptive analgesia through the caudal epidural route provides good postoperative pain relief in spine surgeries. Several precautions have been advised in the literature. Presence of sacral-dural ectasia should be considered a relative contraindication for this procedure. METHODS: A 50-year old woman underwent posterior instrumented spinal fusion for L4-L5 spondylolisthesis under general anesthesia. She received single shot caudal epidural analgesia at the start of the procedure. RESULTS: After complete emergence from anesthesia, she had complete motor and sensory loss below the T12 spinal level, which reversed to normal neurology in 6 hours. Retrospective evaluation of the patient's magnetic resonance imaging showed an ectatic, low lying lumbosacral dural sac which had been overlooked in the initial evaluation. The drugs given by the caudal route have been accidentally administered into the thecal sac causing a brief period of neurologic deficit. CONCLUSION: This unexpected complication has been reported only in the pediatric literature before. It is important to look for the presence of lumbosacral dural anomalies before planning caudal epidural injections in adults also. Sacral dural ectasia and other lumbosacral anomalies must be recognized as contraindications for caudal epidural pre-emptive analgesia for spine surgery. Other modes of postoperative pain relief should be tried in these patients. PMID- 21030894 TI - Bilateral atlantoaxial transarticular screws and atlas laminar hooks fixation for pediatric atlantoaxial instability. AB - STUDY DESIGN: An atlantoaxial fixation using bilateral C1-C2 transarticular screws and C1 laminar hooks was used in 5 pediatric patients, who were then followed up for 12 to 17 months to evaluate the technique. OBJECTIVE: To describe a modified posterior C1-C2 fixation technique and preliminary clinical and radiographic results in 5 pediatric patients. SUMMARY OF BACKGROUND DATA: Conventional posterior atlantoaxial fixations, such as Gallie and Brooks techniques, are frequently associated with high rates of pseudarthrosis and implant failure. The C1-C2 transarticular screw fixation has been shown to be effective in treatment of pediatric atlantoaxial instability, as well as adult atlantoaxial instability; however, this 2-point fixation merely stabilizes the atlantoaxial motion segment laterally. A 3-point fixation, composed with bilateral C1-C2 transarticular screws and C1 laminar hooks, has been developed. METHODS: Five patients with atlantoaxial instability, including 4 males and 1 female, aged 6 to 17 (average 10) years, underwent atlantoaxial fixation using bilateral C1-C2 transarticular screws and C1 laminar hooks during a 2-year period. The surgical technique and treatment procedures were intensively reviewed, and clinical symptoms and imaging appearance were retrospectively evaluated. RESULTS: Clinical follow-ups were obtained for an average of 14.4 (range: 12-17) months. The clinical and radiologic follow-up indicated a stable arthrodesis and offered clinical relief from symptoms for all patients. No neural or vascular impairment related to this technique was observed. CONCLUSION: Fixation of the atlantoaxial articulation using bilateral C1-C2 transarticular screws and C1 laminar hooks appears to be a reliable technique for treatment of pediatric atlantoaxial instability. PMID- 21030895 TI - Uterine fibroid mimicking lumbar radiculopathy: a case report. AB - STUDY DESIGN: Case report. OBJECTIVE: To present the case of a patient with low back and lower extremity pain suspected to result from lumbar radiculopathy but who was discovered to have symptomatic uterine fibroid (UF). SUMMARY OF BACKGROUND DATA: UFs are usually asymptomatic but at times can produce symptoms such as excessive menstrual bleeding, intermenstrual bleeding, dysmenorrhea, pelvic pain, pelvic pressure, bloating, dyspareunia, urinary and bowel disturbance, subfertility, and pregnancy-related complications. In rare cases, they can cause neural impingement leading to lower extremity pain, which can be mistaken for lumbar radiculopathy. METHODS: The patient was a 44-year-old woman who presented with low back pain and left leg pain. Examination suggested lumbar radiculopathy but lumbar magnetic resonance imaging was negative with the exception of a large mass in the pelvis. Pelvic magnetic resonance imaging confirmed this to be a large UF. RESULTS: The patient's symptoms completely resolved following hysterectomy. CONCLUSION: In a female patient with suspected radiculopathy, in whom lumbar imaging is negative, or who does not respond as expected to treatment, UF should be considered. PMID- 21030896 TI - Morphological analysis of the cervical pedicles, lateral masses, and laminae in developmental canal stenosis. AB - STUDY DESIGN: Retrospective cross-sectional study. OBJECTIVE: This study aimed to elucidate the relationship between developmental spinal canal stenosis (DCS) and morphologic features in the cervical spine by comparing the features between DCS and nondevelopmental spinal canal stenosis (NDCS). SUMMARY OF BACKGROUND DATA: DCS is an important predisposing factor for cervical myelopathy. Further, various posterior cervical spinal instrumentations have been developed. However, no study has specifically addressed the cervical posterior morphology of DCS. METHODS: A total of 52 consecutive patients underwent cervical spine computed tomography myelography. Axial images of the largest pedicle diameter were selected from C3 to C7 vertebrae and 260 images were analyzed. The following parameters were measured: spinal canal longitudinal diameter (SCLD), spinal canal transverse diameter, osseous spinal canal area, dural sac area, spinal cord area, pedicle outer width, pedicle axis length, pedicle transverse angulation, lateral mass longitudinal diameter, lateral mass transverse diameter, lamina outer width, and lamina axis length. The participants were classified into 2 groups: DCS group (SCLD <12 mm at any level) and NDCS group (SCLD ?12 mm at all levels). RESULTS: The mean osseous spinal canal area and dural sac area at C3-C5 in the DCS group were less than those in the NDCS group. The mean spinal cord area did not differ significantly at C3-C7 between the groups. The mean pedicle outer width at C6 and C7 in the DCS group was less than that in NDCS group. The mean lateral mass transverse diameter at C5 and mean lateral mass longitudinal diameter at C3, C5, and C6 in the DCS group were less than those in the NDCS group. CONCLUSION: Myelopathy is expected to progress in patients with DSC and these patients with severe neurologic symptoms may need cervical operation. However, posterior screw insertions should be considered more carefully than in NDCS patients. PMID- 21030897 TI - Analysis of spinopelvic parameters in lumbar degenerative kyphosis: correlation with spinal stenosis and spondylolisthesis. AB - STUDY DESIGN: Retrospective study. OBJECTIVE: To define the relationship between pelvic parameters and lumbar spinal disorders including spinal stenosis, spondylolisthesis, and lumbar degenerative kyphosis (LDK). SUMMARY OF BACKGROUND DATA: Although numerous studies have investigated the relationship between various lumbar spinal disorders and spinal parameters previously, none has reported on the relationship with LDK. METHODS: The present study analyzed 211 patients (163 females and 48 males) with spinal stenosis (n = 57), degenerative spondylolisthesis (n = 78), spondylolytic spondylolisthesis (n = 34), and LDK (n = 42). Lateral standing radiograph of the whole spine was analyzed with a dedicated software allowing calculation of the following parameters: pelvic incidence (PI), sacral slope (SS), pelvic tilt (PT), lumbar lordosis (LL), thoracic kyphosis (TK), and sagittal vertical axis. RESULTS: Significant differences in the pelvic parameter were observed between the groups. The mean PI in males (49.6 degrees ) was less than that in females (57.3 degrees ) (P < 0.05). PI was found to be proportional to SS, PT, and LL (P < 0.001). PT was inversely proportional to TK and LL (P < 0.001). Analysis revealed the values of SS, LL, and TK to be significantly higher and those of PT and the PT/PI ratio to be significantly lower in LDK than in the other groups. Values of PI, SS, and LL, but not PT, were significantly higher in subjects of LDK with Takemitsu type 1 than in those with type 2. PI was shown to possess statistically significant correlation to SS, PT, LL, and PT/PI ratio but not to TK or sagittal vertical axis. CONCLUSION: PI has a direct influence on the variable lumbar curvature in LDK. PI and SS may be complementary factors in determining the subtype of LDK, as PT appears to be relatively constant between the different subtypes of LDK. PMID- 21030898 TI - Interferon alfa-2b for recurrent and metastatic giant cell tumor of the spine: report of two cases. AB - STUDY DESIGN: Case report. OBJECTIVE: To demonstrate that interferon alfa-2b is a therapeutic option for obtaining long-term control of recurrent and metastatic giant cell tumor of spine. SUMMARY OF BACKGROUND DATA: Interferon alfa served as angiogenesis inhibitor and has been successfully used to treat giant cell tumor of long bones and facial bones. Up to date, no report is found with regard to the use of interferon as a stand-alone treatment for unresectable, recurrent, and metastatic giant cell tumor originated from the spine. METHODS: A 29-year-old woman with C1 and C2 giant cell tumor was treated by radiotherapy, intralesional curet, and chemotherapy orderly. Tumor recurred after 2 years. A second curet was undertaken. Tumor recurred second time and caused severe spinal cord compression. Lung metastasis was diagnosed simultaneously. A 24-year-old man with recurrent giant cell tumor of T5 and T6 was treated by spondylectomy of T5 and T6. Six months later, a giant metastatic lesion was found in sacrococcygeal region, which was excised and proved to be giant cell tumor of bone. Four months later, 2 recurrent lesions were found beside the rectum. Interferon alfa-2b at a dose of 3,000,000 U/m was then administered subcutaneously everyday for both patients for 3.5 and 3 years, respectively. RESULTS: No major complications related to the use of interferon occurred. The lesion in C1-C2 of the first patient regressed steadily and was restricted and encircled within the lateral mass. The metastatic lesions in the lungs also significantly reduced. The pararectal lesions of the second patient disappeared completely. CONCLUSION: Interferon therapy may be an effective and safe treatment for spine giant cell tumor recurrence and metastasis in soft tissue. The effectiveness may be time and dosage dependent. PMID- 21030899 TI - The effects of exogenous crosslinking on hydration and fluid flow in the intervertebral disc subjected to compressive creep loading and unloading. AB - STUDY DESIGN: In vitro study of genipin crosslinking effect on disc water content changes under compressive loading and unloading. OBJECTIVE: To investigate the influence of collagen crosslinking on hydration and fluid flow in different regions of intact discs, and to evaluate the nutritional implications. SUMMARY OF BACKGROUND DATA: Age-related reductions of nutrient supply and waste product removal are critically important factors in disc pathogenesis. Diffusion and fluid flow are blocked by subchondral bone thickening, cartilaginous endplate calcification, loss of hydrophilic proteoglycans, and clogging of anular pores by degraded matrix molecules. Previous studies demonstrated increased hydraulic permeability and macromolecular transport through crosslinked collagenous matrices. Genipin has also demonstrated the capability to increase retention of proteoglycans. METHODS: A total of 57 bovine lumbar motion segments were divided randomly into phosphate buffered saline and 0.33% genipin-soaked treatment groups. Water content changes were measured using a mass-loss technique in 3 intervertebral disc regions following successive stages of compressive loading and unloading (post-treatment, after 1 hour 750 N compression, and after a subsequent 24-hour period of nominal loading). Net flow of fluid into or out of a region was determined from the percentage change in mean water content from successive groups. RESULTS: Fluid flow to and from the nucleus doubled with genipin crosslinking. Relative to the buffer-only controls, overall net fluid flow increased 103% in the nucleus pulposus, 36% in the inner anulus, and was 31% less in the outer anulus of genipin treated discs. CONCLUSION: The effects of genipin crosslinking on matrix permeability and proteoglycan retention can alter hydration levels and fluid flow in the intervertebral disc. Resulting increases in fluid flow, including a doubling of flow to and from the nucleus, could lead to enhanced nutritional inflow and waste product outflow for the disc, and may have implications for emerging cell-based therapies. PMID- 21030900 TI - Predicting the outcome of selective thoracic fusion in false double major lumbar "C" cases with five- to twenty-four-year follow-up. AB - STUDY DESIGN: Retrospective radiographic and clinical study. OBJECTIVE: To examine the long-term outcome of selective thoracic fusion (STF) performed for lumbar "C" modifier curves in adolescent idiopathic scoliosis. SUMMARY OF BACKGROUND DATA: The efficacy of STF in lumbar "C" false double major curves is controversial. We examined the 5- to 24-year outcomes of patients with "C" lumbar curves who underwent STF at a single institution to determine which factors help predict successful outcome. METHODS: Thirty-two patients (age, 14.8 +/- 2.0 years) with a lumbar "C" modifier underwent primary STF and had minimum 5-year follow-up (mean, 6.8 years). All patients were fused distally to either T12 or L1. At latest follow-up, 18 were considered successful (group S), 2 required reoperation to accommodate worsening deformity (group R), and 12 were considered marginal outcomes (group M), as defined by >3 cm coronal imbalance (n = 5), >5 mm worsening of lumbar apical vertebra translation compared with preoperative (n = 4), >1 Nash-Moe grade worsening of lumbar apical vertebra rotation (n = 1), >10 degrees thoracolumbar junction kyphosis which was at least 5 degrees worse than preoperative (n = 5), and lumbar Cobb angle >5 degrees worse than preoperative (n = 2). Clinical outcomes were determined by Scoliosis Research Society (SRS)-30 at final follow-up. RESULTS: Of the multiple factors considered, 2-month postoperative standing lumbar sagittal alignment was most predictive for long term outcome (P < 0.019 by Kruskal-Wallis ANOVA). Satisfactory outcomes had statistically significantly greater T12-S1 lordosis than those that were marginal (64.8 degrees (group S) vs. 52.0 degrees (group M); P = 0.014) or required reoperation (64.8 degrees [group S] vs. 38.0 degrees [group R]; P < 0.001). Traditionally considered variables such as apical vertebra rotation, apical vertebra translation, Cobb angle magnitudes, coronal and sagittal balance, and their respective thoracic-to-lumbar ratios were not independently significant. CONCLUSION: Selective thoracic fusions performed for lumbar "C" modifier scoliotic deformities generally have excellent long-term radiographic and SRS-30 outcomes at 5- to 24-year follow-up. Care should be taken to ensure that overcorrection of the thoracic curve is not performed beyond the ability of the lumbar curve to compensate. Furthermore, consideration of selective thoracic fusion should not be ruled out simply because the patient may have a somewhat stiff lumbar curve based on side-bending radiographs. PMID- 21030902 TI - Diagnostic testing and treatment of low back pain in United States emergency departments: a national perspective. AB - STUDY DESIGN: This study is an analysis of the National Hospital Ambulatory Medical Care Survey (NHAMCS), a large sample representative of all emergency department (ED) visits throughout the United States. OBJECTIVE: To use NHAMCS to describe the frequency of ED visits for the treatment of low back pain, and the diagnostic and therapeutic strategies employed by emergency clinicians. SUMMARY OF BACKGROUND DATA: Low back pain is common in the general population. While it accounts for 2.5% of all outpatient office visits, the role of the ED has yet to be described. METHODS: We included cases if they had both a reason for visit related to back pain and a primary ED discharge ICD9 code consistent with low back pain. The outcomes included frequency of ED use, and frequency of various diagnostic and therapeutic strategies. Individual patient visits are weighted so that data can be extrapolated to all ED visits throughout the United States. RESULTS: Low back pain related disorders caused 2.63 million (95% CI: 2.32, 2.93 million) annual ED visits in the US. Of all patients with low back pain, 30.5% (28.1, 32.9) had a plain radiograph; 9.6% (95% CI: 7.2, 12.6) had a CT or MRI in 2006 compared with 3.2% (95% CI: 2.0, 5.1) in 2002 (P for trend <0.01). Age and type of insurance were associated with advanced imaging, though geographic region was not. Of medications either administered in the ED or prescribed at discharge, the most frequently used classes were opioids (61.0%, 95% CI: 58.4, 63.5), followed by nonsteroidal anti-inflammatory drugs (49.9%, 95% CI: 47.2, 52.7) and muscle relaxants (43.1%, 95% CI: 40.4, 45.8). CONCLUSION: Low back pain related disorders are a frequent cause of ED visit. Diagnostic imaging is performed in one-third of all patients. There was a strong secular trend in use of advanced imaging; patients were nearly 3 times as likely to receive a CT or MRI in 2006 as they were 4 years earlier. Although opioids were administered or prescribed to two-thirds of patients, use of therapeutic agents was generally in keeping with guideline recommendations. PMID- 21030901 TI - SWISSspine: the case of a governmentally required HTA-registry for total disc arthroplasty: results of cervical disc prostheses. AB - STUDY DESIGN: Prospective multicenter observational case-series. OBJECTIVE: The goal of the SWISSspine registry is to generate evidence about the safety and efficiency of these Medtech innovations. SUMMARY OF BACKGROUND DATA: The Swiss federal office of public health required a mandatory nationwide HTA-registry for cervical total disc arthroplasty (TDA), among other technologies, to decide about reimbursement of these interventions. METHODS: Between March 2005 and June 2008, 808 interventions with implantation of 925 discs from 5 different suppliers were performed. Surgeon-administered outcome instruments were primary intervention, implant, and follow-up forms; patient self-reported measures were EQ-5D, COSS, and a comorbidity questionnaire. Data are recorded perioperative, at 3 months and 1 year postoperative, and annually thereafter. RESULTS. There was significant and clinically relevant reduction of neck (preoperative/postoperative 59.3/24.8 points) and arm pain (preoperative/postoperative 64.9/17.6) on visual analogue scale (VAS) and consequently decreased analgesics consumption. Similarly, quality of life (QoL) improved from preoperative 0.42 to postoperative 0.82 points on EQ 5D scale. There were 4 intraoperative complications and 23 revisions during the same hospitalization for 691 monosegmental TDAs, and 2 complications and 6 revisions for 117 2-level surgeries. A pharmacologically treated depression was identified as important risk factor for achieving a clinically relevant pain alleviation >20 points on VAS. Two-level surgery resulted in similar outcomes compared with the monosegmental interventions. CONCLUSION: Cervical TDA appeared as safe and efficacious in short-term pain alleviation, consequent reduction of pain killer consumption, and in improvement of QoL. A clinically relevant pain reduction of >=20 points was most probable if patients had preoperative pain levels >=40 points on VAS. A pharmacologically treated depression and 2-level surgery were identified as risk factors for less pronounced pain alleviation or QoL improvement. PMID- 21030903 TI - Recombinant phenotyping of cytomegalovirus sequence variants detected after 200 or 100 days of valganciclovir prophylaxis. AB - BACKGROUND: In a phase III controlled trial IMproved Protection Against Cytomegalovirus in Transplantation (IMPACT) comparing 200 with 100 days of valganciclovir prophylaxis in 318 cytomegalovirus D+/R- kidney transplant recipients, an equal number of patients (n=3 per arm) had known ganciclovir resistance mutations detected during viral breakthrough. In addition, many other viral sequence variants were observed that were of unknown significance for ganciclovir resistance. Recombinant phenotyping was performed to determine whether the previously uncharacterized genotypic changes affected ganciclovir susceptibility, especially in those receiving the longer duration of prophylaxis. METHODS: Sequences encoding individual amino acid substitutions in the UL97 kinase or UL54 DNA polymerase gene were transferred by recombination into a cloned cytomegalovirus laboratory strain, followed by reporter-based yield reduction phenotypic assay of the resulting virus for ganciclovir susceptibility. RESULTS: Twenty-six uncharacterized amino acid substitutions were detected, 2 in UL97 and 24 in UL54. All 10 substitutions in the 200-day arm and 9 of 17 substitutions in the 100-day arm (prioritized based on location and conservation) were selected for phenotyping; one substitution was detected in both subsets. Results were generated for nine of ten 200-day and eight of nine 100-day substitutions, with no substitution demonstrating a significant reduction in ganciclovir susceptibility. The two remaining amino acid substitutions, both in UL54, were not evaluated because of poor viral viability. CONCLUSION: Phenotypic evaluation of previously uncharacterized viral genotypes in the 200-day valganciclovir prophylaxis group showed no evidence of an increased incidence of genotypic ganciclovir resistance when compared with those in the 100-day prophylaxis group. PMID- 21030904 TI - Anti-angiotensin type 1 receptor antibodies associated with antibody mediated rejection in donor HLA antibody negative patients. AB - BACKGROUND: Angiotensin type 1 receptor (AT1R) mediates most physiologic and pathophysiologic actions of its endogenous ligand, angiotensin II, with overactivity leading to vascular remodeling and hypertension. Antibodies to AT1R are implicated in several vascular pathologies. The aim of our study was to determine the impact of antibody to AT1R on clinical outcomes including antibody mediated rejection (AMR), with or without C4d deposition, in patients whose sera contained no donor human leukocyte antigen (HLA)-specific antibody (HLA-DSA). METHODS: Pretransplant sera from 97 recipients and sera obtained at the time of acute rejection (AR) were tested by Luminex-based single-antigen bead assays to determine HLA-DSA and antibodies to major histocompatibility class I chain related gene A (MICA). The presence of antibody to AT1R was determined by a cell based ELISA method using a cutoff of 17 units to distinguish high from low binding. RESULTS: Sera from 63 recipients were determined to have no HLA-DSA and no donor-specific MICA antibodies pretransplant and at the time of AR, and 16 of these recipients were diagnosed with AR including 7 with AMR and 9 with cellular AR (cell-mediated rejection). High-binding AT1R antibodies were identified for six of seven in the AMR+ group and zero of nine in the cell-mediated rejection+ group (P=0.0009). CONCLUSIONS: A strong association was observed between the presence of high binding to AT1R and AMR in recipients whose sera contained no antibody to donor HLA or MICA. Assessing the AT1R antibody status along with the HLA-DSA provides additional information to determine the immunologic risk for recipients. PMID- 21030905 TI - Two-year outcomes in thoracic transplant recipients after conversion to everolimus with reduced calcineurin inhibitor within a multicenter, open-label, randomized trial. AB - BACKGROUND: Use of the mammalian target of rapamycin inhibitor everolimus with an accompanying reduction in calcineurin inhibitor (CNI) exposure has shown promise in preserving renal function in maintenance thoracic transplant patients, but robust, long-term data are required. METHODS: In a prospective, open-label, multicenter study, thoracic transplant recipients more than or equal to 1 year posttransplant with mild-to-moderate renal insufficiency were randomized to continue their current CNI-based immunosuppression or convert to everolimus with predefined CNI exposure reduction. After a 12-month core trial, patients were followed up to month 24 after randomization. RESULTS: Of 245 patients who completed the month 12 visit, 235 patients (108 everolimus and 127 controls) entered the 12-month extension phase. At month 24, mean measured glomerular filtration rate had increased by 3.2+/-12.3 mL/min from the point of randomization in everolimus-treated patients and decreased by 2.4+/-9.0 mL/min in controls (P<0.001), a difference that was significant within both the heart and lung transplant subpopulations. During months 12 to 24, 5.6% of everolimus patients and 3.1% of controls experienced biopsy-proven acute rejection (P=0.76). There were no significant differences in the rate of adverse events or serious adverse events (including pneumonia) between groups during months 12 to 24. CONCLUSIONS: Converting maintenance thoracic transplant recipients to everolimus with low-exposure CNI results in a renal benefit that is sustained to 2 years postconversion, with significantly improved measured glomerular filtration rate in both heart and lung transplant patients. Despite reductions of more than 50% in CNI exposure, there was no marked loss of efficacy. The safety profile of the everolimus-based regimen was acceptable. PMID- 21030906 TI - Synthesis of oligodeoxynucleotides using fully protected deoxynucleoside 3' phosphoramidite building blocks and base recognition of oligodeoxynucleotides incorporating N3-cyano-ethylthymine. AB - Oligodeoxynucleotide (ODN) synthesis, which avoids the formation of side products, is of great importance to biochemistry-based technology development. One side reaction of ODN synthesis is the cyanoethylation of the nucleobases. We suppressed this reaction by synthesizing ODNs using fully protected deoxynucleoside 3'-phosphoramidite building blocks, where the remaining reactive nucleobase residues were completely protected with acyl-, diacyl-, and acyl oxyethylene-type groups. The detailed analysis of cyanoethylation at the nucleobase site showed that N3-protection of the thymine base efficiently suppressed the Michael addition of acrylonitrile. An ODN incorporating N3 cyanoethylthymine was synthesized using the phosphoramidite method, and primer extension reactions involving this ODN template were examined. As a result, the modified thymine produced has been proven to serve as a chain terminator. PMID- 21030907 TI - Antibacterial effects of the essential oils of commonly consumed medicinal herbs using an in vitro model. AB - The chemical composition and antibacterial activity of essential oils from 10 commonly consumed herbs: Citrus aurantium, C. limon, Lavandula angustifolia, Matricaria chamomilla, Mentha piperita, M. spicata, Ocimum basilicum, Origanum vulgare, Thymus vulgaris and Salvia officinalis have been determined. The antibacterial activity of these oils and their main components; i.e. camphor, carvacrol, 1,8-cineole, linalool, linalyl acetate, limonene, menthol, a-pinene, b pinene, and thymol were assayed against the human pathogenic bacteria Bacillus subtilis, Enterobacter cloacae, Escherichia coli O157:H7, Micrococcus flavus, Proteus mirabilis, Pseudomonas aeruginosa, Salmonella enteritidis, S. epidermidis, S. typhimurium, and Staphylococcus aureus. The highest and broadest activity was shown by O. vulgare oil. Carvacrol had the highest antibacterial activity among the tested components. PMID- 21030908 TI - Free radical scavenging activity and characterization of sesquiterpenoids in four species of Curcuma using a TLC bioautography assay and GC-MS analysis. AB - The sesquiterpenoids are one of major groups of antioxidants in Curcuma besides curcuminoids. However, the real substances contributing to the antioxidant activity are still unknown. In this paper, the antioxidant activity of sesquiterpenoids in four species and two essential oils from Curcuma genus was determined and compared based on TLC separation and DPPH bioautography assay. Their antioxidant capacities were quantitatively evaluated using densitometry with detection at 530 nm (lambda(reference )= 800 nm) using vitamin C as reference. The results showed that Curcuma longa rhizomes had the highest antioxidant capacity while C. phaeocaulis presented the lowest one among the four species of Curcuma. Moreover, essential oil of C. wenyujin showed higher antioxidant potential than that of C. longa. The main TLC bands with antioxidant activity of the four species of Curcuma were collected and characterized using GC MS, and thus curzerene, furanodiene, alpha-turmerone, beta-turmerone and beta sesquiphellandrene were determined as major sesquiterpenoids with antioxidant activity in Curcuma. PMID- 21030909 TI - Antifungal activity of the essential oil of Illicium verum fruit and its main component trans-anethole. AB - In order to identify natural products for plant disease control, the essential oil of star anise (Illicium verum Hook. f.) fruit was investigated for its antifungal activity on plant pathogenic fungi. The fruit essential oil obtained by hydro-distillation was analyzed for its chemical composition by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). trans Anethole (89.5%), 2-(1-cyclopentenyl)-furan (0.9%) and cis-anethole (0.7%) were found to be the main components among 22 identified compounds, which accounted for 94.6% of the total oil. The antifungal activity of the oil and its main component trans-anethole against plant pathogenic fungi were determined. Both the essential oil and trans-anethole exhibited strong inhibitory effect against all test fungi indicating that most of the observed antifungal properties was due to the presence of trans-anethole in the oil, which could be developed as natural fungicides for plant disease control in fruit and vegetable preservation. PMID- 21030910 TI - Synthesis and characterization of a Ru(II) complex with functionalized phenanthroline ligands having single-double linked anthracenyl and 1-methoxy-1 buten-3-yne moieties. AB - Two series of bidentate polypyridine ligands, made of phenanthroline chelating subunits having substituted mono-and di-anthracenyl groups, and 1-methoxy-1-buten 3-yne at the 4 and 7-positions with the corresponding heteroleptic Ru(II) complex have been synthesized and characterized. The complex is formulated as [(Ru(L(1))(L(2))(NCS)(2))], (where L(1 )= 4-(9-dianthracenyl-10-(2,3 dimethylacrylic acid)-7-(9-anthracenyl-10-(2,3-dimethylacrylic acid)-1,10 phenanthroline and L(2) = 4,7-bis(1-methoxy-1-buten-3-yne)-1,10-phenanthroline). The Ru(II) complex shows characteristic broad and intense metal-to-ligand charge transfer (MLCT) bands absorption and appreciable photoluminescence spanning the visible region. The ligands and complex were characterized by FT-IR, 1H, 13C NMR spectroscopy, UV-Vis, photoluminescence and elemental analysis (see in supplementary materials). The anchoring groups in both ligands have allowed an extended delocalization of acceptor orbital of the metal-to-ligand charge transfer (MLCT) excited state. PMID- 21030911 TI - Synthesis of a highly luminescent three-dimensional pyrene dye based on the spirobifluorene skeleton. AB - We have synthesized a highly luminescent (log e > 5.0, F > 0.9) pyrene dye based on a spirobifluorene skeleton [2,2',7,7'-tetrakis(7-tert-butyl-1-pyrenyl)-9,9' spirobi[9H-fluorene; 4-PySBF]. The use of spirobifluorene prevents fluorescence quenching by intramolecular energy transfer and/or electron transfer among the chromophores in the excited state. The emission spectra of 4-PySBF exhibited a red shift of 20 nm in comparison to a model compound [9,9'-dioctyl-2,7-bis(7-tert butyl-1-pyrenyl)-9H-fluorene; 2-PyF], but its UV-Vis spectrum remained unchanged. PMID- 21030912 TI - Synthesis and application in polypropylene of a novel of phosphorus-containing intumescent flame retardant. AB - A novel phosphorus-containing triazine oligomer poly(2-morpholinyl-4-penta erythritol phosphate-1,3,5-triazine) (PMPT) was synthesized as a kind of tri component intumescent flame retardant (IFR). The chemical structure of PMPT was characterized by FTIR, 1H-NMR and 31P-NMR, and the mechanical and flammability properties of FR-PP were measured. The FTIR results showed that the expected chemical reactions had happened at each step. The 1H-NMR and 31P-NMR spectra also agreed with the chemical structure of PMPT. The slight effect of PMPT on the mechanical properties of FR-PP suggested that PMPT and PP are compatible. The high limited oxygen index (LOI) values of FR-PP revealed that PMPT was an efficient IFR and there was the synergistic effect between PMPT and ammonium polyphosphate/ pentaerythritol (APP/PER). PMID- 21030915 TI - Endoscopy and the surgeon. PMID- 21030916 TI - Sleeve lobectomy: current indications and future directions. AB - Sleeve lobectomy was initially conceived as an alternative to pneumonectomy for patients with low-grade, centrally located lesions and limited cardiopulmonary reserve. Over the last several decades, advances in patient selection criteria and surgical techniques have allowed sleeve lobectomy to evolve from a compromise to pneumonectomy to first line intervention for centrally located lesions of all grades. Although more challenging than pneumonectomy, long-term outcomes and cost effective measures favor sleeve lobectomy. The use of sleeve lobectomy has been expanded for locally advanced disease, and results remain superior to alternative procedures. Current literature has also shown evidence supporting the use of neoadjuvant treatment and minimally invasive techniques. It is likely that future results will continue to improve making sleeve lobectomy an even more attractive treatment option for qualifying patients. PMID- 21030913 TI - The biosynthesis of artemisinin (Qinghaosu) and the phytochemistry of Artemisia annua L. (Qinghao). AB - The Chinese medicinal plant Artemisia annua L. (Qinghao) is the only known source of the sesquiterpene artemisinin (Qinghaosu), which is used in the treatment of malaria. Artemisinin is a highly oxygenated sesquiterpene, containing a unique 1,2,4-trioxane ring structure, which is responsible for the antimalarial activity of this natural product. The phytochemistry of A. annua is dominated by both sesquiterpenoids and flavonoids, as is the case for many other plants in the Asteraceae family. However, A. annua is distinguished from the other members of the family both by the very large number of natural products which have been characterised to date (almost six hundred in total, including around fifty amorphane and cadinane sesquiterpenes), and by the highly oxygenated nature of many of the terpenoidal secondary metabolites. In addition, this species also contains an unusually large number of terpene allylic hydroperoxides and endoperoxides. This observation forms the basis of a proposal that the biogenesis of many of the highly oxygenated terpene metabolites from A. annua - including artemisinin itself - may proceed by spontaneous oxidation reactions of terpene precursors, which involve these highly reactive allyllic hydroperoxides as intermediates. Although several studies of the biosynthesis of artemisinin have been reported in the literature from the 1980s and early 1990s, the collective results from these studies were rather confusing because they implied that an unfeasibly large number of different sesquiterpenes could all function as direct precursors to artemisinin (and some of the experiments also appeared to contradict one another). As a result, the complete biosynthetic pathway to artemisinin could not be stated conclusively at the time. Fortunately, studies which have been published in the last decade are now providing a clearer picture of the biosynthetic pathways in A. annua. By synthesising some of the sesquiterpene natural products which have been proposed as biogenetic precursors to artemisinin in such a way that they incorporate a stable isotopic label, and then feeding these precursors to intact A. annua plants, it has now been possible to demonstrate that dihydroartemisinic acid is a late-stage precursor to artemisinin and that the closely related secondary metabolite, artemisinic acid, is not (this approach differs from all the previous studies, which used radio isotopically labelled precursors that were fed to a plant homogenate or a cell free preparation). Quite remarkably, feeding experiments with labeled dihydroartemisinic acid and artemisinic acid have resulted in incorporation of label into roughly half of all the amorphane and cadinane sesquiterpenes which were already known from phytochemical studies of A. annua. These findings strongly support the hypothesis that many of the highly oxygenated sesquiterpenoids from this species arise by oxidation reactions involving allylic hydroperoxides, which seem to be such a defining feature of the chemistry of A. annua. In the particular case of artemisinin, these in vivo results are also supported by in vitro studies, demonstrating explicitly that the biosynthesis of artemisinin proceeds via the tertiary allylic hydroperoxide, which is derived from oxidation of dihydroartemisinic acid. There is some evidence that the autoxidation of dihydroartemisinic acid to this tertiary allylic hydroperoxide is a non-enzymatic process within the plant, requiring only the presence of light; and, furthermore, that the series of spontaneous rearrangement reactions which then convert this allylic hydroperoxide to the 1,2,4-trioxane ring of artemisinin are also non-enzymatic in nature. PMID- 21030914 TI - Reduction of diphenyl diselenide and analogs by mammalian thioredoxin reductase is independent of their gluthathione peroxidase-like activity: a possible novel pathway for their antioxidant activity. AB - Since the successful use of the organoselenium drug ebselen in clinical trials for the treatment of neuropathological conditions associated with oxidative stress, there have been concerted efforts geared towards understanding the precise mechanism of action of ebselen and other organoselenium compounds, especially the diorganyl diselenides such as diphenyl diselenide, and its analogs. Although the mechanism of action of ebselen and other organoselenium compounds has been shown to be related to their ability to generally mimic native glutathione peroxidase (GPx), only ebselen however has been shown to serve as a substrate for the mammalian thioredoxin reductase (TrxR), demonstrating another component of its pharmacological mechanisms. In fact, there is a dearth of information on the ability of other organoselenium compounds, especially diphenyl diselenide and its analogs, to serve as substrates for the mammalian enzyme thioredoxin reductase. Interestingly, diphenyl diselenide shares several antioxidant and neuroprotective properties with ebselen. Hence in the present study, we tested the hypothesis that diphenyl diselenide and some of its analogs (4,4'-bistrifluoromethyldiphenyl diselenide, 4,4'-bismethoxy-diphenyl diselenide, 4.4'-biscarboxydiphenyl diselenide, 4,4'-bischlorodiphenyl diselenide, 2,4,6,2',4',6'-hexamethyldiphenyl diselenide) could also be substrates for rat hepatic TrxR. Here we show for the first time that diselenides are good substrates for mammalian TrxR, but not necessarily good mimetics of GPx, and vice versa. For instance, bis-methoxydiphenyl diselenide had no GPx activity, whereas it was a good substrate for reduction by TrxR. Our experimental observations indicate a possible dissociation between the two pathways for peroxide degradation (either via substrate for TrxR or as a mimic of GPx). Consequently, the antioxidant activity of diphenyl diselenide and analogs can be attributed to their capacity to be substrates for mammalian TrxR and we therefore conclude that subtle changes in the aryl moiety of diselenides can be used as tool for dissociation of GPx or TrxR pathways as mechanism triggering their antioxidant activities. PMID- 21030917 TI - Surgical treatment of metachronous nonsmall cell lung cancer. AB - PURPOSE: We report surgical results of metachronous nonsmall cell lung cancer (NSCLC). METHODS: We report mortality and analyze prognostic factors for overall survival in patients with metachronous NSCLC at Nippon Medical School from July 1982 to July 2008. RESULTS: Thirty-three out of 1726 patients (1.9%) who underwent lung resection had metachronous NSCLC. Mortality rate was 10%. On univariate analyses, the different histologies at the first and second operations were the only significant poor prognostic factor. Twenty-two patients (73%) had the same histology at the first and second operations: adenocarcinoma in 18 (60%) and squamous cell carcinoma in 4 (13%). Their actuarial 5- and 10-year overall survivals were both 71%, compared to 47% and 16% for patients with different histology (p = 0.0174). Sex (p = 0.1742), locations of the first and second cancers (p = 0.3957), operative procedures in patients with p-stage I at the second operation (p = 0.2782), pathological stage at the first operation (p = 0.5958), and pathological stage at the second operation (p = 0.0609) were not prognostic factors. Different histology at the first and second operations was significant based on a multivariate analysis (Hazard ratio: 3.918; p value: 0.0269; 95% confidence interval: 1.169-13.131). The actuarial 5- and 10-year overall survivals for the first cancer was 86% and 64%, compared to 65% and 45% for the second (p = 0.0609). CONCLUSIONS: Our study shows that a surgical approach is beneficial for patients with metachronous NSCLC. Good prognosis in patients with the same histology may support the current criteria of metachronous NSCLC mainly based on the histology. PMID- 21030918 TI - Induction chemoradiation therapy with cisplatin plus irinotecan followed by surgical resection for superior sulcus tumor. AB - PURPOSE: In this study, we retrospectively evaluate the safety and efficacy of induction chemoradiation using cisplatin plus irinotecan followed by surgical resection for superior sulcus tumor (SST). METHODS: We reviewed the records of four patients with solitary, previously untreated T3-4, N0-1 superior sulcus nonsmall cell lung cancers. Patients received two cycles of chemotherapy, cisplatin and irinotecan, every 4 weeks. Radiotherapy directed at the tumor was administered with a split schedule at the total dose of 40 Gy in 20 fractions. Thoracotomy was performed 4 weeks after completion of the chemoradiation. RESULTS: The toxicities of chemoradiation were mainly hematologic and were well tolerated. Complete resection could be performed in all cases, and there was no postoperative mortality. At present, all the patients remain alive, and one has a local recurrence. CONCLUSION: This trimodality approach is a safe and effective approach for the local control of SST. Further studies are necessary to confirm the results. PMID- 21030919 TI - Morphological investigations of type A aortic dissection. AB - PURPOSE: The aim of this study was to analyze systematically the morphology of aortal segments of Type A dissection. METHODS: Nineteen patients were operated on for Type A dissection in the Department of Thoracic, Cardiac, and Vascular Surgery in Goettingen, Germany, from January 2002 to January 2005. All diagnoses were confirmed by transesophageal echocardiography and computed tomography of the chest. All taken aortic segments were examined by the conventional histological and electron microscopical method. RESULTS: Besides subadventitial hyperplasia of collagen filaments, the preparations showed hyperplasia of endothelial cells with loose cellular junctions, desquamation of endothelial cells, and morphological changes of endothelial cells with villius development, as well as signs of aortitis. CONCLUSION: The present results arouse suspicion of local inflammation of the aortic wall, but with moderate progress under strong hyperplasia. Because of rupture of the intima, the inflammation appears as an acute disease. PMID- 21030921 TI - Short and midterm results of epi and endocardial cryoablation. AB - BACKGROUND: Cryoablation is a new surgical technique for the treatment of atrial fibrillation. Because long-term results are scarce, we report on our findings with this antiarrhythmic therapy. METHODS: Forty-three patients (men: 22; women: 21) with paroxysmal (20 patients) or permanent (23) atrial fibrillation underwent different cardiac procedures with simultaneous cryoablation from 2002 to 2007. Cryoablation was performed epicardially with the SurgiFrostTM Cryosurgical system in patients with closed-heart procedures and endocardially in patients with mitral valve surgery. Data were collected by reviewing charts of the patients. Follow-up data were obtained by phoning the general practitioners and/or cardiologists of the patients. RESULTS: The mean age of the patients was 66.2 +/- 9.0 years. Fifteen different operations were performed, with coronary artery bypass grafting and mitral valve replacement occurring most frequently. Four patients (9.3%) died postoperatively, 22 were discharged with sinus rhythm (56.4%), and the others demonstrated atrial fibrillation (43.6%). A cardioversion performed on 9 patients postoperatively was successful in 5. All patients were treated with phenprocoumon and amiodarone for a minimum of 6 months postoperatively. Follow-up data were collected 26 +/- 15 months after surgery. The number of patients with sinus rhythm had increased to 26 (66.7%), whereas 13 (33.3%) patients still suffered from atrial fibrillation. CONCLUSION: Cryoablation seems to be an effective tool in the treatment of atrial fibrillation. PMID- 21030920 TI - Effects of original crystalloid cardioplegia followed by additional blood cardioplegia: treatments for prolonged cardiac arrest. AB - PURPOSE: The efficacy of combination treatment of original cold crystalloid cardioplegia (SHA solution; St. Thomas + Histidine + ATP + oxygen) and additional blood cardioplegia was studied in patients who required cardiac arrest time of 120 minutes or longer. METHODS: One hundred and thirty-six patients were included in this study. Patients were divided into two groups according to the cardiac arrest time: S group (cardiac arrest time: 120-149 minutes, n = 81); L group (150 180 minutes, n = 55). Just after cross-clamping of the ascending aorta, 800 ml of SHA solution was infused in an antegrade fashion. Cold-blood cardioplegia was initiated after two hours of cardiac arrest. RESULTS: Six (4%) of the 136 patients died after surgery, 3 in each group. Two critical patients with ischemic cardiomyopathy died of cardiac failure after coronary artery bypass grafting (CABG), and 4 died of noncardiac morbidity. The mean value of postoperative maximum creatine phosphokinase-MB (CPK-MB) in dead patients was 47 IU/L in the S group and 75 IU/L in the L group. The peak CPK-MB values exceeded 100 IU/L in one out of 6 patients who died after surgery. CONCLUSIONS: Combination treatment using original SHA solution and additional blood cardioplegia was effective in patients who required prolonged cardiac arrest. PMID- 21030922 TI - A surgical case of quadruple lung cancer. AB - The patient was a 50-year-old male psychiatrist with a history of smoking 3 packs of cigarettes per day for 30 years. Chest computed tomography (CT) showed a nodular shadow in the left S6 segment in April 2002, for which thoracoscopic partial resection of the lung was performed. Because adenocarcinoma was diagnosed by intraoperative frozen sectioning, a left lower lobectomy and lymph node dissection were performed. The pathological diagnosis was adenocarcinoma with mixed subtypes (AMS, pT1N0M0). Cytologically, the tumor cells exhibited tall columnar eosinophilic cytoplasm. In March 2005, chest CT showed a nodular shadow in the right S3 segment, and thoracoscopic partial resection of the lung was performed. Histopathological examination revealed AMS (pT1N0M0). Cytologically, cancer cells showed cuboidal cytoplasm. In November 2007, a nodular shadow appeared in the right S4 segment on chest CT, and thoracoscopic partial resection of the middle lobe and the portion of the upper lobe that had adhered to the middle lobe was performed. Histologically, the middle-lobe tumor was solid adenocarcinoma with mucin (pT1N0M0). Although no gross tumor could be identified in the upper lobe, histological examination revealed nonmucinous bronchioloalveolar carcinoma (pT1N0M0). The patient is currently following a favorable course. Herein, we report a surgical case of quadruple lung cancer. PMID- 21030923 TI - Confirmation of a variant lingular vein anatomy during thoracoscopic surgery. AB - Variations in pulmonary veins can have a serious effect on patients undergoing lung surgery. But few clinicians are familiar with patients who have these variations, and few have been reported in the left pulmonary vein. We report the case of a lung cancer patient with a variant anatomy in the inferior segment of the lingular vein (V5) that drained into the left inferior pulmonary vein. A preoperative review of the patient's three-dimensional 64-row multidetector computed tomography (3D MDCT) imaging showed that the variant vein (V5) was draining from the inferior lingular segment into the upper side of the inferior pulmonary vein, which was also observed on conventional CT films. This variant anatomy was confirmed during a thoracoscopic left upper lobectomy. Furthermore, the superior segment (V6) of the inferior pulmonary vein drained into the basal part of the inferior pulmonary vein, but not into the superior side where V5 in this patient was drained. The postoperative course was uneventful, and the patient was discharged on postoperative day 10. Preoperative 3D MDCT imaging of the pulmonary vein allowed good visualization of the patient's vascular variant during surgery, and it contributed to safe thoracic surgery, especially in a thoracoscopic operation. PMID- 21030924 TI - Giant saccular aneurysm of coronary arteriovenous fistula to the main pulmonary artery: intraoperative assessment by using fluorescent imaging. AB - Coronary arteriovenous fistulas (CAF) and coronary artery aneurysms (CAA) are uncommon, but their detection has recently increased. In this case we succeeded in identifying the residual shunt flow by using an intraoperative fluorescence imaging technique with indocyanine green after surgical treatment. The photodynamic eye imaging system is based on fluorescence of indocyanine green. This is the first report to identify residual shunt flow with such a giant coronary aneurysm by using fluorescence imaging, and the result indicates that this technique is useful for acceptance as one of the examinations to evaluate CAAs. Furthermore, it may be useful for the detection of shunt cases, such as congenital heart disease. PMID- 21030925 TI - Three young osteosarcoma patients with small adenocarcinoma or atypical adenomatous hyperplasia of the lung. AB - Three young osteosarcoma patients with adenocarcinoma (AD) or atypical adenomatous hyperplasia (AAH) of the lung are reported. A 14-year-old male patient with femoral osteosarcoma had solitary AD (case 1); a 23-year-old female patient with femoral osteosarcoma had AAH and lung metastasis (case 2); and a 17 year-old male patient with humeral osteosarcoma had AD and lung metastasis of osteosarcoma (case 3). They have been the youngest patients with lung cancer or AAH in our hospital. The maximum diameter of each lung tumor on computed tomography (CT) was 0.5, 0.6, and 0.5 cm, respectively. On immunohistochemical analyses, the p53 was positive in both AD and osteosarcoma and negative in both AAH and osteosarcoma. On genomic analyses, p53 mutation was detected in only one osteosarcoma (case 3). Epidermal growth factor receptor (EGFR) mutations, short in-frame deletion in exon 19, and insertion in exon 20 were found in AD, but not in AAH or osteosarcoma. There was no apparent genomic relationship between AD/AAH and osteosarcoma in the young patients in this study. Advances in CT and its applications to osteosarcoma patients as a method of assessing lung metastasis might contribute in large part to the detection of AD/AAH in patients younger than 30. PMID- 21030926 TI - Familial spontaneous pneumothorax in two adult siblings with Marfan syndrome. AB - A 21-year-old adult with previously diagnosed Marfan syndrome (MS) was admitted to our hospital complaining of chest pains that resulted from a complete left spontaneous pneumothorax (SP). A chest roentgenogram showed a 70% pneumothorax on the left side. Because for 8 days chest tube drainage did not ameliorate the air leak, and also because a computed tomography (CT) scan showed many cystic opacities at the apical lung, a bullectomy was performed under video-assisted thoracic surgery (VATS). The patient's family history revealed that his father and two brothers had MS. Three family members had a unilateral SP, and his two siblings were treated under VATS and showed no evidence of recurrent pneumothorax. The simultaneous occurrence of MS and SP in these two patients suggests the possibility that both abnormalities in pulmonary connective tissue (e.g., collagen I) and the tall figure are responsible for the development of SP in MS patients. Because our patients and those in published reports are few in number, no definitive conclusion can be drawn about the relationship between SP and MS. Herein we describe a rare case of familial SP in two adult siblings with MS. PMID- 21030927 TI - Aortic valve replacement in a patient with alpha-thalassemia. AB - Cardiac valve disease resulting from elastic tissue defects has been demonstrated in patients with beta-thalassemia; however, valve disorders of patients with alpha-thalassemia have been rarely discussed. We present the case of a patient with alpha-thalassemia and severe aortic regurgitation with left ventricular dysfunction. The patient underwent successful aortic valve replacement with mechanical prosthesis. Histopathology of the excised valve showed elastic tissue disruption and chronic thrombus on the ventricular side. Hypercoagulative states have been observed in patients with alpha-thalassemia as beta-thalassemia; therefore special attention should be taken in perioperative anticoagulation therapy. PMID- 21030928 TI - Redo CABG for ACS via the left thoracotomy using the PAS-port system to the descending thoracic aorta: a case report. AB - A 74-year-old female patient with left main trunk (LMT) and triple vessel disease underwent coronary artery bypass graft (CABG) surgery. The patient began to experience exertional dyspnea. A coronary artery angiogram confirmed a severe stenosis in the proximal side of the saphenous vein graft (SVG). The patient had impending infarction immediately after the unsuccessful attempt for percutaneous coronary intervention, which resulted in an emergent CABG procedure. A left thoracotomy at the 4th intercostal space was made with the patient in the right lateral position. We then interrupted the use of intra-aortic balloon pumping (IABP), confirmed on transesophageal echocardiography (TEE) that the balloon was in a position distal to the target anastomosis site, and made a proximal anastomosis using the PAS-Port system (Cardica, Redwood City, CA, USA). After its successful deployment, IABP was repositioned back and resumed. The distal anastomosis was made to the previously bypassed graft. The patient had no postoperative myocardial damage or complications and was discharged on postoperative day 21. A redo CABG for post-CABG acute coronary syndrome patient was thought to be an extreme high risk; however, the operative time could be minimized by using the PAS-Port system, which enabled a safe redo CABG with left thoracotomy. PMID- 21030929 TI - Successful surgical treatment of acute type A aortic dissection complicated with distal arch aneurysm. AB - We report successful surgical treatment in a case of acute type A aortic dissection complicated with distal arch aneurysm. A 74-year-old man presenting with sudden posterior headache was found by enhanced computed tomography to have an ascending aortic dissection (type A) and a distal arch aneurysm of 69 mm in maximal minor axis diameter. We performed total arch replacement, employing a four-branched graft and elephant trunk anastomosis through a median sternotomy. Because the aneurysm was not effectively thrombo-excluded, we performed descending aorta replacement using the elephant trunk through the left fifth intercostal space on the 44th postoperative day. The postoperative course was uneventful. PMID- 21030930 TI - Bentall operation with saphenous vein graft for a Takayasu's aortitis patient. AB - Takayasu's aortitis patients present a variety of symptoms, including angina pectoris, aortic valve regurgitation, and aortic branch stenosis. The case described in this paper primarily presented with angina pectoris. Close investigation revealed a left coronary artery ostium lesion, an aortic root aneurysm, and a mild aortic regurgitation. The patient underwent a modified Bentall operation with saphenous vein graft (SVG) replacement of the left main trunk. The postoperative course was uneventful, and the patient received oral steroid therapy. SVG is a useful option in treating aortic root aneurysm with an ostium lesion. PMID- 21030931 TI - Atherosclerotic pseudoaneurysm of the left subclavian artery: a case report. AB - A subclavian artery aneurysm is rare. We report the case of a 61-year-old man with a history of hypertension and angina pectoris who was diagnosed with an atherosclerotic aneurysm of the left subclavian artery. An incidental computed tomography scan revealed a 37-mm saccular aneurysm adjacent to both the proximal left subclavian artery and the distal aortic arch. He underwent an aneurysmectomy with total aortic arch replacement via a median sternotomy. Operative findings revealed that the aneurysm had originated from the left subclavian artery and was located 1 cm distal to the ostium. The final pathological diagnosis was a pseudoaneurysm. PMID- 21030932 TI - Prosthetic sleeve reinforcing for juxtarenal abdominal aortic aneurysm: experience of 30 cases. AB - OBJECTIVE: Endovascular repair remains a challenge in the treatment of juxtarenal abdominal aortic aneurysms (AAAs); open surgery is now the treatment of choice. Because the proximal anastomosis involves a fragile aortic wall and renal ischemic time is correlated with postoperative renal dysfunction, simple and secure reinforcing of the suture line is indispensable in juxtarenal AAA repair. Our report describes the efficacy of prosthetic sleeve reinforcing (PSR) for this repair. PATIENTS AND METHODS: From 2005 to 2009, 30 patients, including 4 with ruptured aneurysms, underwent juxtarenal AAA repair with PSR. We reviewed their in-hospital and midterm outcomes. RESULTS: Mean renal ischemic time was 26 +/- 5.5 min. Mean hospital length of stay was 19 days; including 4 cases of ruptured juxtarenal AAA, there were no mortalities. Three patients with preoperative renal dysfunction, including 2 with aneurysmal rupture, required temporary renal replacement therapy. The overall survival rate was 93% (28/30). There was no case of postoperative graft-related complications, including anastomotic pseudoaneurysm and graft-enteric fistula. CONCLUSION: PSR enables secure and prompt proximal anastomosis, preventing postoperative morbidity and late graft related complications. We conclude that PSR could be a valuable method for juxtarenal AAA repair. PMID- 21030933 TI - [Assessment of tigecycline use economic impact in first-line therapy for complicated intra-abdominal infections in an Intensive Care Unit]. AB - The aim of this study was to determine the economic impact on hospital budget expenditure for two different prescribing practices: use of tigecycline in second or first-line therapy (when appropriate). This empirical study was carried out at the Intensive Care Unit (ICU) (Chief, Dr. Alberto Costantini), Ospedali Riuniti, Ancona. Cost determination was based on health care processes as revealed by field survey at the ICU. Mapping of the health care processes was neither derived from official protocols nor from an ex-post analysis of medical records but rather directly from descriptions of the processes as referred by the ICU physicians and health care staff, and then summarized in flow charts and approved by the ICU chief. The assumption was that tigecycline, because of its broader spectrum of action, would more probably clear infections when used in the first course of antibiotic therapy. Notwithstanding this advantage, tigecycline has a higher daily dose cost than first-line antibiotics. This study compared the higher costs incurred by the use of tigecycline as a first-line antibiotic versus potential savings obtained with such use, also in view of the prevention of possible treatment failures and the additional cost of administering a second course of antibiotic therapy, wherein the result would depend on the number of preventable treatment failures. The analysis concludes with a discussion and graphic illustrations comparing the differential probable treatment success which would render the two treatment alternatives economically indifferent. PMID- 21030934 TI - Aspirin for the prevention of cardiovascular morbidity. AB - Aspirin (ASA) use for secondary prevention in patients with cardiovascular (CV) disease is well established through its beneficial effects on the reduction of myocardial infarction, ischemic stroke and CV mortality. This beneficial effect of ASA seems to consistently outweigh the risk in most patient subsets. Current guidelines endorse ASA for primary prevention of CV events in adults who are at moderate-high risk of CV morbidity. Recent emerging data on the efficacy and safety of ASA conflicts with former randomized clinical trials and raises concerns regarding the validity of these recommendations. The following manuscript describes the data emerging from contemporary trials regarding the efficacy and safety of ASA in various patient subsets. The authors propose certain strategies to enhance safety and efficacy in order to augment the beneficial effects of ASA along with other modalities of primary prevention for suitable candidates. When contemplating ASA prescription for primary prevention of CV events, physicians should carefully weigh the potential benefits of risk reduction versus likelihood of harm, mostly related to bleeding complications. PMID- 21030935 TI - Antithrombotic treatment in acute coronary syndromes. AB - Platelet activation and thrombin formation are integral in the pathophysiology of acute coronary syndrome. Currently available pharmacotherapies inhibit the cascade of platelet aggregation and activation, and prevent thrombin formation to limit platelet-fibrin complex formation, thus maintaining coronary patency and ultimately improving clinical outcomes. This is a rapidly evolving field with next-generation antithrombotic combinations aimed at achieving the "Holy Grail" of improved anti-ischemic efficacy whilst minimizing bleeding risk. Our review article focuses on the use of antithrombotic agents for the contemporary management of patients with ACS. PMID- 21030936 TI - Diabetic specific aspects in antithrombotic therapy in patients with coronary artery disease. AB - The use of combined antithrombotic medication in optimal dosages is mandatory for diabetic patients. Moreover, specific antiplatelet therapy in DM has been shown to reduce early and late atherothrombotic events in patients referred for elective and acute angiography and intervention as well as for secondary prevention of recurrent ischemic events in patients with coronary artery disease (CAD). Among these antiplatelet agents prasugrel has been recently demonstrated to lower adverse events in diabetic patients with acute coronary syndromes (ACS) significantly more effective than clopidogrel without increasing severe bleeding hazards. Also glycoprotein IIb-IIIa receptor inhibitors (GPI) had a greater effect in diabetic subjects with ACS undergoing percutaneous coronary intervention (PCI) on adverse clinical events compared to non-diabetics. In contrast to antiplatelet therapy, all commercially available antithrombins except enoxaparin have been shown to be equal or less effective in diabetics compared to non-diabetics. Enoxaparin was superior to unfractionated heparin (UFH) in reducing adverse events in diabetics with acute ST-elevation myocardial infarction (STEMI) undergoing thrombolytic therapy. The role of several new antithrombins, i.e. direct factor Xa inhibitors or direct antithrombins in diabetic patients with stable or unstable CAD is still under investigation. PMID- 21030937 TI - Young at heart. An update on cardiac regeneration. AB - Cardiovascular disease remains one of the most important causes of mortality. Over the past decades important advances have been made in prevention and treatment of acute complications after myocardial infarction (MI). As a result, the number of patients that acutely die from MI has been reduced. Current treatments can not prevent the loss of cardiac contractility caused by cardiomyocyte death, and therefore patients that do survive MI are prone to develop progressive impaired cardiac function, which may lead to heart failure. Cell-based therapy has been proposed as a potential new therapy to prevent progression to end-stage heart failure by (re)generating contractile tissue in the damaged heart. During the last years many different cell sources have been studied extensively for their cardiomyogenic differentiation capacity in vitro and in vitro. These cells include several populations of cardiac-derived progenitor cells as well as mesenchymal stem cells derived from different sources. It has become clear that not only the origin, but also the "age" of a cell is an important determinant of its plasticity. Therefore, special attention is paid to the difference in developmental state of the cell sources and the consequences for their differentiation capacity and therapeutic applicability. Furthermore, we provide future perspectives for several aspects of cell-based therapy that could be optimized in order to enhance the regeneration of the heart. PMID- 21030938 TI - Endothelial dysfunction: potential clinical implications. AB - Vascular endothelium is responsible for the secretion of several substances exerting anti-atherogenic effects. Endothelial damage is also crucial for the progress of atherosclerosis and risk factors for atherosclerosis represent crucial factors associated with endothelial dysfunction. Studies have shown that patients with cardiovascular disease are characterized by impaired endothelial function (EF). Therefore, several agents have been proposed as potential modulators of EF. Most of the available approaches include pharmaceutical agents routinely used such as statins, angiotensin converting enzyme inhibitors, antioxidants, L-arginine, insulin sensitizers or others still under investigation such as tetrahydrobiopterin or folic acid (folate). Despite of the fact that there are several strategies aiming to improve endothelial dysfunction by enhancing nitric oxide bioavailability, it is still unclear whether they could be beneficial at a clinical level. PMID- 21030940 TI - Incidence of end-stage renal disease attributed to diabetes among persons with diagnosed diabetes --- United States and Puerto Rico, 1996-2007. AB - During 2007, approximately 110,000 persons in the United States and Puerto Rico began treatment for end-stage renal disease (ESRD) (i.e., kidney failure requiring dialysis or transplantation). Diabetes is the leading cause of ESRD in the United States, accounting for 44% of new cases in 2007. Although the number of persons initiating treatment for kidney failure each year who have diabetes listed as a primary cause (ESRD-D) has increased since 1996, ESRD-D incidence among persons with diagnosed diabetes has declined since 1996. To determine whether this decline occurred in every U.S. region and in every state, CDC analyzed 1996-2007 data from the U.S. Renal Data System (USRDS) and the Behavioral Risk Factor Surveillance System (BRFSS). During the period, the age adjusted rate of ESRD-D among persons with diagnosed diabetes declined 35% overall, from 304.5 to 199.1 per 100,000 persons with diagnosed diabetes, and declined in all U.S. regions and in most states. No state showed a significant increase in the age-adjusted ESRD-D rate. Continued awareness of risk factors for kidney failure and interventions to improve diabetes care are needed to sustain and improve these trends. PMID- 21030939 TI - [Nimesulide: 25 years later]. AB - The first marketing authorization for nimesulide was approved in Italy in 1985. After one quarter of a century we evaluate its peculiar characteristics compared with other NSAIDs. Nimesulide is the only NSAID related to the arylsulfonamide class and is a "COX-2 preferential NSAIDs", because despite having a prevalent effect on COX-2, has a balanced action on both cyclooxygenase. The gastrointestinal absorption is rapid and complete and explains the short onset of action. Nimesulide is rapidly distributed in the synovial fluid, where it persists longer than in the blood, thus contributing to effectiveness of the drug in pain control. From the standpoint of safety, nimesulide arises NSAIDs with lower risk of upper gastrointestinal bleeding thanks to its preferential activity on COX-2. In relation to the risk of severe hepatic reactions, the benefit/risk profile of nimesulide was considered by european regulatory authorities similar to other NSAIDs. Respecting international guidelines, the use of nimesulide in pain management, as that of other NSAIDs, must be considered as an alternative therapy when paracetamol is ineffective, or where the pain is caused or supported by an inflammatory process. PMID- 21030941 TI - Global routine vaccination coverage, 2009. AB - The widespread use of vaccines has greatly improved global public health, preventing millions of childhood hospitalizations and deaths each year. Vaccination of children also is projected to avert adult deaths through the prevention of hepatitis B (HepB) virus--related chronic liver disease and liver cancer and human papilloma virus--related cervical cancer. When the World Health Organization (WHO) began the Expanded Programme on Immunization in 1974, <5% of the world's children had been fully vaccinated with bacille Calmette-Guerin (BCG), diphtheria-tetanus-pertussis (DTP) vaccine, oral poliovirus vaccine, and measles-containing vaccine (MCV) during the first year of life. Since then, increased vaccination coverage has resulted in substantial reductions in morbidity and mortality, including a >99% decline in polio incidence since 1988, with eradication on the horizon, and a 78% decline in measles-associated mortality from 2000 to 2008 With the introduction of Haemophilus influenzae type b (Hib) vaccine, HepB vaccine, pneumococcal conjugate vaccine (PCV), and rotavirus vaccine into many countries' routine vaccination schedules, further reductions in morbidity and mortality are expected. However, based on an annual global birth cohort of approximately 130 million, an estimated 23 million infants worldwide still do not receive the benefits of routine vaccination (i.e., 3 doses of DTP during the first year of life). The Global Immunization Vision and Strategy (GIVS), developed in 2005 by WHO and UNICEF, assists countries in strengthening immunization programs and vaccinating more persons. GIVS aims to achieve 90% national 3-dose DTP (DTP3) coverage by age 12 months in all countries, and 80% coverage in every district or equivalent administrative unit by 2010 (and to sustain these levels through 2015). This report summarizes global routine vaccination coverage during 2000--2009 and progress toward achieving GIVS goals. PMID- 21030942 TI - Rapid diagnostic tests for malaria ---Haiti, 2010. AB - Plasmodium falciparum malaria is endemic to Haiti and remains a major concern for residents, including displaced persons, and emergency responders in the aftermath of the January 12, 2010 earthquake. Microscopy has been the only test approved in the national policy for the diagnosis and management of malaria in Haiti; however, the use of microscopy often has been limited by lack of equipment or trained personnel. In contrast, malaria rapid diagnostic tests (RDTs) require less equipment or training to use. To assist in the timely diagnosis and treatment of malaria in Haiti, the Ministry of Public Health and Population (MSPP), in collaboration with CDC, conducted a field assessment that guided the decision to approve the use of RDTs. This data-driven policy change greatly expands the opportunities for accurate malaria diagnosis across the country, allows for improved clinical management of febrile patients, and will improve the quality of malaria surveillance in Haiti. PMID- 21030943 TI - Notes from the field: Vibrio mimicus infection from consuming crayfish --- Spokane, Washington, June 2010. AB - On June 24, 2010, the Spokane (Washington) Regional Health District (SRHD) was notified of two hospitalized patients under intensive care with severe dehydration whose stool specimens yielded Vibrio mimicus. CDC was asked to assist with the environmental and epidemiologic investigation. Investigators learned that both persons had consumed crayfish on June 20, 2010. The previous day, live crayfish obtained from an online seafood company had been boiled and served warm at a party. The chef reported that the boiled crayfish were served out of a cooler that had contained live crayfish, and the cooler had not been cleaned before being used to serve the cooked crayfish. After the party, the remaining crayfish were refrigerated overnight in different containers and served cold as leftovers the following evening on June 20. PMID- 21030945 TI - Dueling models in head and neck tumor formation. AB - The two leading models that have been used to explain tumor progression in head and neck squamous cell carcinoma (HNSCC) are the stochastic clonal evolution model, in which many tumor cells are individually capable of recapitulating the entire tumor mass, and the cancer stem hierarchy model, in which only rare totipotential tumor stem cells can recapitulate the tumor. In this issue, Cameron et al use cell surface marker and clonal cell analyses in combination with a xenotransplant approach to provide data that support the stochastic clonal evolution model in HNSCC. This interpretation is subject, however, to limitations inherent in the experimental approach employed. Understanding the basis of tumor progression in HNSCC as well as other cancers should be further explored because of important implications for effective treatments. PMID- 21030946 TI - Impact of clock gene Bmal1 deficiency on nutritionally induced obesity in mice. AB - To evaluate the hypothesis that the clock gene Bmal1 (brain and muscle arnt like protein-1) plays a role in the development of obesity, 5-week-old male Bmal1 deficient (Bmal1(-/-)) mice and wild-type littermates (Bmal1(+/+)) were kept on a high-fat diet (HFD) for 15 weeks. Despite an initial accelerated weight gain of Bmal1(-/-) mice, body weight and subcutaneous (SC) and gonadal (GON) adipose tissue mass were comparable to Bmal1(+/+) mice at the end of the diet period. Noninvasive magnetic resonance imaging scanning revealed a modest increase in fat content in Bmal1(-/-) mice after 10 weeks of HFD, whereas at the start and the end of the HFD feeding no differences were observed between both genotypes. After 15 weeks of HFD, adipocyte and blood vessel size and density were similar for Bmal1(+/+) and Bmal1(-/-) mice. However, the weight of major organs was significantly reduced in Bmal1(-/-) mice, confirming the premature ageing phenotype. Thus, we hypothesize that an initial accelerated increase in body weight and fat mass of Bmal1(-/-) mice on HFD may have been offset by the effect of premature ageing on organ weight, resulting in comparable weights after 15 weeks of HFD. PMID- 21030947 TI - Physical activity patterns using accelerometry in the National Weight Control Registry. AB - The National Weight Control Registry (NWCR) was established in 1993 to examine characteristics of successful weight-loss maintainers. This group consistently self-reports high levels of physical activity. The aims of this study were to obtain objective assessments of physical activity in NWCR subjects and compare this to physical activity in both normal-weight and overweight controls. Individuals from the NWCR (n = 26) were compared to a never obese normal-weight control group matched to the NWCR group's current BMI (n = 30), and an overweight control group matched to the NWCR group's self-reported pre-weight-loss BMI (n = 34). Objective assessment of physical activity was obtained for a 1-week period using a triaxial accelerometer. Bouts of moderate-to-vigorous physical activity (MVPA) >=10 min in duration, as well as nonbout MVPA (bouts of MVPA 1-9 min in duration) were summed and characterized. NWCR subjects spent significantly (P = 0.004) more time per day in sustained bouts of MVPA than overweight controls (41.5 +/- 35.1 min/day vs. 19.2 +/- 18.6 min/day) and marginally (P = 0.080) more than normal controls (25.8 +/- 23.4). There were no significant differences between the three groups in the amount of nonbout MVPA. These results provide further evidence that physical activity is important for long-term maintenance of weight loss and suggest that sustained volitional activity (i.e., >=10 min in duration) may play an important role. Interventions targeting increases in structured exercise may be needed to improve long-term weight-loss maintenance. PMID- 21030948 TI - Bypassing the duodenum does not improve insulin resistance associated with diet induced obesity in rodents. AB - Roux-en-y gastric bypass (RYGB) surgery rapidly improves glucose tolerance and reverses insulin resistance in obese patients. It has been hypothesized that this effect is mediated by the diversion of nutrients from the proximal small intestine. We utilized duodenal-jejunal bypass (DJB) as a modification of gastric bypass to determine the effect of nutrient diversion from the foregut without gastric restriction on insulin resistance in obese rats. The effects of DJB or Sham surgery on glucose homeostasis were determined in both high-fat-fed Long Evans and Wistar rats. Body weight and food intake were measured weekly postoperatively, and body composition was monitored before and after surgery. Glucose tolerance was tested before and as early as 1 month postoperation; additionally, in Wistar rats, insulin sensitivity was determined by a hyperinsulinemic-euglycemic clamp (HIEC). DJB did not affect body weight, body composition, glucose tolerance, or insulin concentrations over the period of the study. The average glucose infusion rate (GIR) during the HIEC was 6.2 +/- 1.16 mg/kg/min for Sham rats compared to 7.2 +/- 1.71 mg/kg/min for DJB rats (P = 0.62), and neither endogenous glucose production (EGP; P = 0.81) nor glucose utilization (glucose disappearance (R(d)), P = 0.59) differed between DJB and Sham rats. DJB does not affect insulin resistance induced by a high-fat diet in Long-Evans and Wistar rats. These data suggest that duodenal bypass alone is an insufficient mechanism to alter insulin sensitivity independent of weight loss in obese, nondiabetic rodents. PMID- 21030949 TI - A rapid and efficient route to benzazole heterocycles. AB - This protocol describes a rapid, high-yielding, microwave-mediated route that affords benzazole heterocycles in high crude purity and represents a significant advancement toward an environmentally friendly reaction. The reaction of aryl isothiocyanates with o-nucleophilic anilines produces thiourea intermediates that, in the presence of a carbodiimide-functionalized resin, cyclize to benzazoles with the safe removal of one equivalent of hydrogen sulfide. This procedure takes ~ 8.5 h to complete: 1-3 h for setup, 4.5 h for benzazole formation and 2 h for workup and purification. PMID- 21030950 TI - Cell separation using cryogel-based affinity chromatography. AB - In cell affinity chromatography, type-specific cell separation is based on the interaction between cell-surface receptors and an immobilized ligand on a stationary matrix. This protocol describes the preparation of monolithic polyacrylamide and polydimethylacrylamide cryogel affinity matrices that can be used as a generic type-specific cell separation approach. The supermacroporous monolithic cryogel has highly interconnected large pores (up to 100 MUm) for convective migration of large particles such as mammalian cells. In this protocol, they are functionalized to immobilize a protein A ligand by a two-step derivatization of epoxy-containing cryogel monolith (reaction with ethylenediamine and glutaraldehyde). Target cells were labeled with specific antibodies and then they were captured in the cryogel through affinity with protein A. These specifically captured cells were recovered in high yields while retaining their viability by mechanical squeezing of the spongy and elastic cryogel matrices. The suggested cell separation protocol takes < 30 min for complete separation on a preprepared protein A-immobilized cryogel column. PMID- 21030951 TI - Distinguishing cell types or populations based on the computational analysis of their infrared spectra. AB - Infrared (IR) spectroscopy of intact cells results in a fingerprint of their biochemistry in the form of an IR spectrum; this has given rise to the new field of biospectroscopy. This protocol describes sample preparation (a tissue section or cytology specimen), the application of IR spectroscopy tools, and computational analysis. Experimental considerations include optimization of specimen preparation, objective acquisition of a sufficient number of spectra, linking of the derived spectra with tissue architecture or cell type, and computational analysis. The preparation of multiple specimens (up to 50) takes 8 h; the interrogation of a tissue section can take up to 6 h (~100 spectra); and cytology analysis (n = 50, 10 spectra per specimen) takes 14 h. IR spectroscopy generates complex data sets and analyses are best when initially based on a multivariate approach (principal component analysis with or without linear discriminant analysis). This results in the identification of class clustering as well as class-specific chemical entities. PMID- 21030952 TI - Raster image correlation spectroscopy in live cells. AB - Raster image correlation spectroscopy (RICS) is a noninvasive technique to detect and quantify events in a live cell, including concentration of molecules and diffusion coefficients of molecules; in addition, by measuring changes in diffusion coefficients, RICS can indirectly detect binding. Any specimen containing fluorophores that can be imaged with a laser scanning microscope can be analyzed using RICS. There are other techniques to measure diffusion coefficients and binding; however, RICS fills a unique niche. It provides spatial information and can be performed in live cells using a conventional confocal microscope. It can measure a range of diffusion coefficients that is not accessible with any other single optical correlation-based technique. In this article we describe a protocol to obtain raster scanned images with an Olympus FluoView FV1000 confocal laser scanning microscope using Olympus FluoView software to acquire data and SimFCS software to perform RICS analysis. Each RICS measurement takes several minutes. The entire procedure can be completed in ~2 h. This procedure includes focal volume calibration using a solution of fluorophores with a known diffusion coefficient and measurement of the diffusion coefficients of cytosolic enhanced green fluorescent protein (EGFP) and EGFP-paxillin. PMID- 21030954 TI - Measuring behavioral and endocrine responses to novelty stress in adult zebrafish. AB - Several behavioral assays are currently used for high-throughput neurophenotyping and screening of genetic mutations and psychotropic drugs in zebrafish (Danio rerio). In this protocol, we describe a battery of two assays to characterize anxiety-related behavioral and endocrine phenotypes in adult zebrafish. Here, we detail how to use the 'novel tank' test to assess behavioral indices of anxiety (including reduced exploration, increased freezing behavior and erratic movement), which are quantifiable using manual registration and computer-aided video-tracking analyses. In addition, we describe how to analyze whole-body zebrafish cortisol concentrations that correspond to their behavior in the novel tank test. This protocol is an easy, inexpensive and effective alternative to other methods of measuring stress responses in zebrafish, thus enabling the rapid acquisition and analysis of large amounts of data. As will be shown here, fish anxiety-like behavior can be either attenuated or exaggerated depending on stress or drug exposure, with cortisol levels generally expected to parallel anxiety behaviors. This protocol can be completed over the course of 2 d, with a variable testing duration depending on the number of fish used. PMID- 21030955 TI - MeltMADGE for mutation scanning of specific genes in population studies. AB - MeltMADGE reconfigures the mutation scanning process of denaturing gradient gel electrophoresis so that the independent variable is time rather than space and the dependent (denaturing) variable is temperature rather than concentration of chemical denaturant. Use of a thermal ramp enables the use of a homogeneous gel and therefore of high-density arrays of wells such as those of microplate array diagonal gel electrophoresis (MADGE). In this configuration, electrophoresis of products on 10-12 96-well meltMADGE gels can be conducted in a 1- to 2-liter tank in a 1- to 2-h run, enabling the scanning of a target amplicon in over 1,000 subjects simultaneously. Gels are read by imaging the fluorescence of UV-excited ethidium bromide, giving a simple, economical system for identifying rarer sequence variants in target genes; it is suitable for large-scale case-control or population studies and other comparable applications. Different amplicons with similar melting characteristics can also be combined in the same run. PMID- 21030953 TI - An efficient method of directly cloning chimpanzee adenovirus as a vaccine vector. AB - Adenoviral vectors have shown great promise as vaccine carriers and in gene transfer to correct underlying genetic diseases. Traditionally, construction of adenoviral vectors is complex and time consuming. In this paper, we provide an improved method for efficient generation of novel adenoviral vectors by using direct cloning. We introduce a feasible and detailed protocol for the development of chimpanzee adenoviruses (Ads) as molecular clones, as well as for the generation of recombinant virus from the molecular clones. Recombinant viruses are genetically stable and induce potent immune responses in animals. Generation of new Ad molecular clones or new recombinant Ad can be achieved in 2 months or 2 weeks, respectively. PMID- 21030956 TI - Synthesis of peptide macrocycles using unprotected amino aldehydes. AB - This protocol describes a method for synthesizing peptide macrocycles from linear peptide precursors, isocyanides and aziridine aldehydes. The effects of the reaction components on the efficiency of the process are discussed. Macrocyclization is exemplified by the preparation of a nine-membered ring peptide macrocycle. The product is further functionalized by nucleophilic opening of the aziridine ring with a fluorescent thiol. This transformation constitutes a useful late-stage functionalization of a macrocyclic peptide molecule. The experimental section describes the selection of the required starting materials, and the preparation of a representative aziridine-2-carboxaldehyde dimer. The synthesis and isolation of the peptide macrocycle can be accomplished in 6 h, and the ring-opening requires approximately 6-8 h. The aziridine-2-carboxaldehyde reagent is commercially available or can be synthesized from readily available starting materials in approximately 4 d. The strategy described is not limited to the specific peptide, isocyanide, aziridine aldehyde or nucleophile used in the representative synthesis. PMID- 21030957 TI - High-throughput microplate assay for the determination of drug partition coefficients. AB - Partition coefficients (K(p)) of drugs between the phospholipid bilayer and the aqueous phase provide useful information in quantitative structure-activity relationship studies. Hexadecylphosphocholine (HePC) micelles, composed of a zwitterionic hydrophilic surface and a hydrophobic core, mimic the biomembranes and have several advantages over other lipid structures to assess K(p) values. Their preparation is easy, fast and avoids the use of toxic organic solvents, and the output has fewer spectroscopic interferences. Here, we describe a high throughput microplate protocol for assessing the K(p) of drugs using HePC micelles as membrane models and derivative spectrophotometry as the detection technique. Moreover, the time-consuming data treatment to assess K(p) values is easily performed by a dedicated Excel routine developed here and described in detail. The K(p) values of nonsteroidal anti-inflammatory drugs (acemetacin, clonixin, diclofenac and indomethacin) were determined to show the simplicity of the method and to validate this protocol, which provides K(p) values (n = 3) of two drugs in ~ 2 h. PMID- 21030958 TI - Conditionally controlling nuclear trafficking in yeast by chemical-induced protein dimerization. AB - We present here a protocol to conditionally control the nuclear trafficking of target proteins in yeast. In this system, rapamycin is used to heterodimerize two chimeric proteins. One chimera consists of a FK506-binding protein (FKBP12) fused to a cellular 'address' (nuclear localization signal or nuclear export sequence). The second chimera consists of a target protein fused to a fluorescent protein and the FKBP12-rapamycin-binding (FRB) domain from FKBP-12-rapamycin associated protein 1 (FRAP1, also known as mTor). Rapamycin induces dimerization of the FKBP12- and FRB-containing chimeras; these interactions selectively place the target protein under control of the cell address, thereby directing the protein into or out of the nucleus. By chemical-induced dimerization, protein mislocalization is reversible and enables the identification of conditional loss of-function and gain-of-function phenotypes, in contrast to other systems that require permanent modification of the targeted protein. Yeast strains for this analysis can be constructed in 1 week, and the technique allows protein mislocalization within 15 min after drug treatment. PMID- 21030959 TI - Automated microfluidic protein immunoblotting. AB - This protocol describes regional photopatterning of polyacrylamide gels in glass microfluidic devices as a platform for seamless integration of multiple assay steps. The technology enables rapid, automated protein immunoblotting, demonstrated in this study for native western blotting. The fabrication procedure is straightforward and requires approximately 3 h from the start of gel photopatterning to completion of native protein western blotting, a substantial time savings over slab-gel immunoblotting. The assay itself requires less than 5 min. Importantly, all assay stages are programmably controlled by a high-voltage power supply and monitored by an epifluorescence microscope equipped with a charge-coupled device camera. Our approach overcomes severe limitations associated with conventional immunoblotting, including multiple steps requiring manual intervention, low throughput and substantial consumption of reagents. We also describe a simple chemical recycling protocol so that glass chips can be reused. The fabrication technique described forms the basis for a diverse suite of bioanalytical tools, including DNA/RNA blotting and multidimensional separations. PMID- 21030960 TI - Solid-phase synthesis of short alpha-helices stabilized by the hydrogen bond surrogate approach. AB - Stabilized alpha-helices and nonpeptidic helix mimetics have emerged as powerful molecular scaffolds for the discovery of protein-protein interaction inhibitors. Protein-protein interactions often involve large contact areas, which are often difficult for small molecules to target with high specificity. The hypothesis behind the design of stabilized helices and helix mimetics is that these medium sized molecules may pursue their targets with higher specificity because of a larger number of contacts. This protocol describes an optimized synthetic strategy for the preparation of stabilized alpha-helices that feature a carbon carbon linkage in place of the characteristic N-terminal main-chain hydrogen bond of canonical helices. Formation of the carbon-carbon bond is enabled by a microwave-assisted ring-closing metathesis reaction between two terminal olefins on the peptide chain. The outlined strategy allows the synthesis and purification of a hydrogen bond surrogate (HBS) alpha-helix in ~ 1 week. PMID- 21030963 TI - Defining pluripotency. AB - Retroviral marking of single human embryonic stem cells shows that cultures of these cells contain subpopulations with distinct functional properties. PMID- 21030961 TI - Federal policy and the use of pluripotent stem cells. PMID- 21030964 TI - DNA construction: homemade or ordered out? AB - Automation and optimization of DNA construction results in the efficient production of large target sequences. PMID- 21030965 TI - Pacing lightly: optogenetics gets to the heart. PMID- 21030968 TI - FGF23 or PTH: which comes first in CKD ? AB - In the past 40 years, disordered mineral metabolism has been among the most intensely studied areas of nephrology. A June 2010 PubMed search for 'secondary hyperparathyroidism and kidney disease' yielded 5866 references. Among these are papers documenting the development and application of numerous therapeutic agents including calcitriol, vitamin D analogs, phosphate binders, and cinacalcet-that remain in widespread use in the day-to-day management of dialysis patients worldwide. However, almost 6000 papers later, fundamental pathophysiological concepts remain unclear, particularly regarding the early pathogenesis of disordered mineral metabolism. PMID- 21030969 TI - Adaptation of intercalated cells along the collecting duct to systemic acid/base changes. AB - Collecting duct intercalated cells respond to short-term acid/base perturbations by rapidly shuttling H(+)-ATPase to and from the plasma membrane. Purkerson et al. provide information on the regulation of the anion transporters during chronic acidosis and acute recovery (alkalosis). They found that the major mechanism for both acute and chronic states is regulation of both the H(+)-ATPase and the anion exchangers plus changes in the overall expression level of these anion transporters in chronic adaptation. PMID- 21030970 TI - IgG4-related tubulointerstitial nephritis. AB - Tubulointerstitial nephritis (TIN) is a disease pattern with heterogeneous causes. Recently a specific subtype of autoimmune TIN, IgG4-related TIN, has been identified that is part of systemic IgG4-related disease/ autoimmune pancreatitis. On biopsy, this TIN shows an IgG4+ plasma cell-rich infiltrate, akin to the pancreatic tissue findings in autoimmune pancreatitis, and may show tubulointerstitial immune complex deposits. Notably, some cases may be mass forming. Recognition of this specific type of TIN can guide appropriate patient therapy. PMID- 21030971 TI - Parathyroid resistance to FGF23 in kidney transplant recipients: back to the past or ahead to the future? AB - Fibroblast growth factor 23 (FGF23) modulates the metabolism of minerals and vitamin D. In chronic kidney disease (CKD), this process is disturbed owing to decreased parathyroid expression of FGF23's receptor complex Klotho-FGF receptor 1. In this issue, Krajisnik and colleagues demonstrate that similar alterations occur in parathyroid glands from kidney transplant recipients in association with a decline in allograft function. Is it possible that these data can be extrapolated to general early-stage CKD patients? PMID- 21030972 TI - Comments on 'a young man with acute kidney injury after exercise'. PMID- 21030973 TI - Index for recognition of early vascular disease. PMID- 21030977 TI - Comments on 'in patients with type 1 diabetes and new-onset microalbuminuria the development of advanced chronic kidney disease may not require progression to proteinuria'. PMID- 21030979 TI - The hypothesis that abnormal BH4 metabolism impairs kidney function. PMID- 21030980 TI - Multinucleated podocytes: a diagnostic clue to cystinosis. PMID- 21030981 TI - PHF6 mutations in adult acute myeloid leukemia. AB - Loss of function mutations and deletions encompassing the plant homeodomain finger 6 (PHF6) gene are present in about 20% of T-cell acute lymphoblastic leukemias (ALLs). Here, we report the identification of recurrent mutations in PHF6 in 10/353 adult acute myeloid leukemias (AMLs). Genetic lesions in PHF6 found in AMLs are frameshift and nonsense mutations distributed through the gene or point mutations involving the second plant homeodomain (PHD)-like domain of the protein. As in the case of T-ALL, where PHF6 alterations are found almost exclusively in males, mutations in PHF6 were seven times more prevalent in males than in females with AML. Overall, these results identify PHF6 as a tumor suppressor gene mutated in AML and extend the role of this X-linked tumor suppressor gene in the pathogenesis of hematologic tumors. PMID- 21030982 TI - The leukemogenic AF4-MLL fusion protein causes P-TEFb kinase activation and altered epigenetic signatures. AB - Expression of the AF4-MLL fusion protein in murine hematopoietic progenitor/stem cells results in the development of proB acute lymphoblastic leukemia. In this study, we affinity purified the AF4-MLL and AF4 protein complexes to elucidate their function. We observed that the AF4 complex consists of 11 binding partners and exhibits positive transcription elongation factor b (P-TEFb)-mediated activation of promoter-arrested RNA polymerase (pol) II in conjunction with several chromatin-modifying activities. In contrast, the AF4-MLL complex consists of at least 16 constituents including P-TEFb kinase, H3K4(me3) and H3K79(me3) histone methyltransferases (HMT), a protein arginine N-methyltransferase and a histone acetyltransferase. These findings suggest that the AF4-MLL protein disturbs the fine-tuned activation cycle of promoter-arrested RNA Pol II and causes altered histone methylation signatures. Thus, we propose that these two processes are key to trigger cellular reprogramming that leads to the onset of acute leukemia. PMID- 21030983 TI - Pre-B-cell leukemias in Btk/Slp65-deficient mice arise independently of ongoing V(D)J recombination activity. AB - The adapter protein Slp65 and Bruton's tyrosine kinase (Btk) are key components of the precursor-B (pre-B) cell receptor (pre-BCR) signaling pathway. Slp65 deficient mice spontaneously develop pre-B-cell leukemia, expressing high levels of the pre-BCR on their cell surface. As leukemic Slp65-deficient pre-B cells express the recombination activating genes (Rag)1 and Rag2, and manifest ongoing immunoglobulin (Ig) light-chain rearrangement, it has been hypothesized that deregulated recombinase activity contributes to malignant transformation. In this report, we investigated whether Rag-induced DNA damage is involved in oncogenic transformation of Slp65-deficient B cells. We employed Btk/Slp65 double-deficient mice carrying an autoreactive 3-83MUdelta BCR transgene. When developing B cells in their bone marrow express this BCR, the V(D)J recombination machinery will be activated, allowing for secondary Ig light-chain gene rearrangements to occur. This phenomenon, called receptor editing, will rescue autoreactive B cells from apoptosis. We observed that 3-83MUdelta transgenic Btk/Slp65 double-deficient mice developed B-cell leukemias expressing both the 3-83MUdelta BCR and the pre BCR components lambda5/VpreB. Importantly, such leukemias were found at similar frequencies in mice concomitantly deficient for Rag1 or the non-homologous end joining factor DNA-PKcs. We therefore conclude that malignant transformation of Btk/Slp65 double-deficient pre-B cells is independent of deregulated V(D)J recombination activity. PMID- 21030984 TI - Non-Hodgkin's lymphoma in adolescents: experiences in 378 adolescent NHL patients treated according to pediatric NHL-BFM protocols. AB - Age-related differences in the distribution, biology and treatment response of non-Hodgkin's lymphoma (NHL) in adolescents remain to be elucidated. The current analyses present clinical parameters and outcomes of adolescents treated in pediatric NHL-BFM trials. Patients were stratified by histological subtype: lymphoblastic lymphoma (LBL); mature B-NHL, including Burkitt's lymphoma/leukemia (BL/B-AL), diffuse B-cell lymphoma (DLBCL-CB) and mediastinal B-cell lymphoma (PMLBL); and anaplastic large cell lymphoma (ALCL). Between October 1986 and December 2007, 2915 patients were registered, including 378 (13%) adolescents (15 18 years) with BL/B-AL (n=101), ALCL (n=74), DLBCL-CB (n=55), T-LBL (n=45), PMLBL (n=24), pB-LBL (n=13) and rare or not-specified NHL subtypes (n=66). The 5-year event-free survival (EFS) was 79+/-2% for adolescents compared with 85+/-1% for patients aged <15 years (P=0.014). EFS was 83+/-7% for adolescents with T-LBL, 82+/-4% with BL/B-AL, 85+/-5% with DLBCL-CB, 57+/-10% with PMLBL and 70+/-6% with ALCL. According to sex, the 5-year EFS in females versus males, respectively, was 70+/-5 versus 83+/-2% overall (P=0.004), 57+/-17 versus 92+/-6% (P=0.0036) for T LBL patients and 71+/-9 versus 97+/-3% (P=0.0067) for DLBCL-CB patients. Adolescents with NHL treated according to pediatric NHL-BFM protocols had an EFS of 79+/-2%, which is marginally inferior to that of children. In adolescents with T-LBL and DLBCL-CB, female sex was associated with a worse prognosis. PMID- 21030985 TI - First oral warfarin alternative approved in the US. PMID- 21030986 TI - Accelerating the pulse of cardiovascular R&D. AB - Renewed commitment to cardiovascular drug development is needed to combat what is likely to be the leading cause of death for the next two decades. How might this be achieved? PMID- 21030987 TI - Modifying protein misfolding. PMID- 21030989 TI - Deal watch: Acceleron and Shire to target the activin receptor pathway for muscular disorders. PMID- 21030990 TI - Trial watch: somatostatin analogue shows promise in Cushing's disease. PMID- 21030991 TI - Deal watch: co-promotion deals: panacea or poison pill? PMID- 21030993 TI - An audience with Patrick Vallance. PMID- 21030994 TI - Location of pharmaceutical innovation: 2000-2009. PMID- 21030995 TI - Velaglucerase alfa. PMID- 21030996 TI - Analgesics: Pain control at the periphery. PMID- 21030997 TI - Fibrotic disease: Targeting the microenvironment. PMID- 21030998 TI - Inflammatory disorders: Constraining the complement cascade. PMID- 21030999 TI - Cancer: Targeting mutant BRAF in metastatic melanoma. PMID- 21031000 TI - Antimalarial drugs: Speeding to a new lead. PMID- 21031001 TI - Utilizing targeted cancer therapeutic agents in combination: novel approaches and urgent requirements. AB - The rapid development of new therapeutic agents that target specific molecular pathways involved in tumour cell proliferation provides an unprecedented opportunity to achieve a much higher degree of biochemical specificity than previously possible with traditional chemotherapeutic anticancer agents. However, the lack of specificity of these established chemotherapeutic drugs allowed a relatively straightforward approach to their use in combination therapies. Developing a paradigm for combining new, molecularly targeted agents, on the other hand, is substantially more complex. The abundance of molecular data makes it possible, at least in theory, to predict how such agents might interact across crucial growth control networks. Initial strategies to examine molecularly targeted agent combinations have produced a small number of successes in the clinic. However, for most of these combination strategies, both in preclinical models and in patients, it is not clear whether the agents being combined actually hit their targets to induce growth inhibition. Here, we consider the initial approach of the US National Cancer Institute (NCI) to the evaluation of combinations of molecularly targeted anticancer agents in patients and provide a description of several new approaches that the NCI has initiated to improve the effectiveness of combination-targeted therapy for cancer. PMID- 21031002 TI - The importance of new companies for drug discovery: origins of a decade of new drugs. AB - Understanding the factors that promote drug innovation is important both for improvements in health care and for the future of organizations engaged in drug discovery research and development. By identifying the inventors of 252 new drugs approved by the US Food and Drug Administration from 1998 to 2007 and their places of work, and also classifying these drugs according to innovativeness, this study investigates the contribution of different types of organizations and regions to drug innovation during this period. The data indicate that drugs initially discovered in biotechnology companies or universities accounted for approximately half of the scientifically innovative drugs approved, as well as half of those that responded to unmet medical needs, although their contribution to the total number of new drugs was proportionately lower. The biotechnology companies were located mainly in the United States. This article presents a comprehensive analysis of these data and discusses potential contributing factors to the trends observed, with the aim of aiding efforts to promote drug innovation. PMID- 21031004 TI - Understanding transport through pharmacological barriers--are we there yet? PMID- 21031005 TI - Multigenerational reproductive toxicology study of ethinyl estradiol (CAS No. 57 63-6) in Sprague-Dawley rats. AB - BACKGROUND: Ethinyl estradiol is a potent synthetic estrogen that is widely prescribed in oral contraceptives and is also used in the treatment of breast and prostate cancer. Ethinyl estradiol is one of a class of chemicals known as"environmental estrogens" which can affect the hormone activities and possibly reproductive function of wildlife and humans through exposure. The NTP conducted a series of studies on three such chemicals to detect if exposure over the course of multiple generations could have any cumulative effect on animals' reproductive systems or development of cancers. This report describes the results of a set of studies in which rats and their offspring were exposed to ethinyl estradiol over the course of four generations. METHODS: The continuous-breeding study began with groups of 35 Sprague-Dawley rats of each sex exposed to ethinylestradiol in their feed at concentrations of 2, 10, or 50 parts per billion (ppb). Control animals received the same feed with no ethinyl estradiol added. Animals from the same dose treatment groups were paired and mated, and 25 litters of pups at each exposure concentration (culled to four males and four females each) were continued on study and given feed containing the same concentration of ethinyl estradiol. The process was repeated through a second and third generation, after which the pups were given control feed only, and two more generations were bred in the same manner and given control feed without ethinyl estradiol. Measures of fertility and reproduction were taken for each generation and tissues from the study animals were examined histopathologically. RESULTS: In all three offspring generations the time to vaginal opening (a measure of onset of puberty) was accelerated in females fed 50 ppb ethinyl estradiol. In the first two offspring generations the estrous cycles of the exposed females were prolonged or aberrant prior to mating. Male rats exposed to ethinyl estradiol had increased rates of mammary gland hyperplasia and mineralization of the kidney tubules. CONCLUSIONS: We conclude that exposure to trace amounts of ethinyl estradiol in the feed showed clear biological activity in male and female rats, including reduced body weights in both sexes, perturbed estrous cycles in females, and induction of mammary gland hyperplasia and kidney tubule mineralization in males. PMID- 21031006 TI - Toxicology and carcinogenesis study of ethinyl estradiol (CAS No. 57-63-6) in Sprague-Dawley rats (feed study). AB - BACKGROUND: Ethinyl estradiol is a potent synthetic estrogen that is widely prescribed in oral contraceptives and is also used in the treatment of breast and prostate cancer. Ethinyl estradiol is one of a class of chemicals known as"environmental estrogens" that can affect the hormone activities and possibly reproductive function of wildlife and humans through exposure. The NTP conducted a series of studies on three such chemicals to detect if exposure over the course of multiple generations could have any cumulative effect on animals' reproductive systems or development of cancers. This report describes the results of a set of studies in which rats were exposed to ethinylestradiol for part or all of the study period and examined at the end of two years. METHODS: The study consisted of three separate study components; in each, animals were exposed to ethinyl estradiol from the time of conception and through weaning through their mothers, who were given ethinyl estradiol in their feed.In one study we gave feed containing 2, 10, or 50 parts per billion (ppb) of ethinyl estradiol to groups of 50 male and female rats from conception through two years. In the second study, groups of 50 male and female rats were given the same feed concentrations up to 20 weeks following birth, followed by untreated feed for the remainder of the two years. In the third study groups of 50 male and female rats were exposed from conception through weaning, and then given untreated feed for the duration of the study. Control animals received the same feed with no ethinyl estradiol added. Enthinyl estradiol is known to cause cancer at higher dose levels; the concentrations given in this study were below the levels of detection by chemical analysis, to determine the possible effects of trace amounts in the environment. At the end of the study tissues from more than 40 sites were examined for every animal. RESULTS: In all three study sets effects were seen in the uterus of female rats. The rates of squamous metaplasia increased in females exposed for two years and in females exposed from conception through weaning; endometrial hyperplasia and atypical focal hyperplasia of the uterus also were increased in females exposed for two years. Uterine stromal polyps were increased in female rats exposed from conception through 20 weeks after birth or from conception through weaning. Male rats exposed from conception through weaning had small increases in the rates of preputial gland tumors and three male rats in that study had rare mammary gland adenomas or carcinomas. CONCLUSIONS: We conclude that exposure to trace amounts of ethinyl estradiol during the period from conception through weaning may have been related to development of uterine stromal polyps in female rats and to preputial gland tumors and mammary gland tumors in male rats. PMID- 21031007 TI - Photocarcinogenesis study of aloe vera [CAS NO. 481-72-1(Aloe-emodin)] in SKH-1 mice (simulated solar light and topical application study). AB - The popular recognition of the Aloe barbadensis Miller (Aloe vera) plant as a therapeutic dermatologic agent has led to the widespread incorporation of Aloe vera leaf extracts in skincare products. Studies have suggested that Aloe vera in skincare preparations may enhance the induction of skin cancer by ultraviolet radiation. A 1-year study was conducted in mice to determine whether the topical application of creams containing Aloe vera plant extracts (aloe gel, whole leaf, or decolorized whole leaf) or creams containing aloe-emodin would enhance the photocarcinogenicity of simulated solar light (SSL). 1-YEAR STUDY: groups of 36 male and 36 female Crl:SKH-1 (hr -/hr -) hairless mice received topical applications of control cream or creams containing 3% or 6% (w/w) aloe gel, whole leaf, or decolorized whole leaf or 7.46 or 74.6 ug/g aloe-emodin to the dorsal skin region each weekday morning. The mice were irradiated with SSL emitted from filtered 6 kW xenon arc lamps each weekday afternoon. The topical applications of creams and irradiance exposures were conducted 5 days per week for a period of 40 weeks. A 12-week recovery/observation period followed the 40-week treatment/exposure period. Additional groups of 36 male and 36 female mice received no cream and were exposed to 0.00, 6.85, 13.70, or 20.55 mJ?CIE/cm2 SSL per day. Mice that received no cream treatment and were exposed to increasing levels of SSL showed significant SSL exposure-dependent decreases in survival and significant increases in the in-life observations of skin lesion onset, incidence, and multiplicity, and significant SSL exposure-dependent increases in the incidences and multiplicities of histopathology-determined squamous cell nonneoplastic skin lesions (squamous hyperplasia and focal atypical hyperplasia) and squamous cell neoplasms (papilloma, carcinoma in situ, and/or carcinoma). Squamous cell neoplasms were not detected in mice that received no SSL exposure. The topical treatment with the control cream of mice that were exposed to SSL did not impart a measurable effect when compared with comparable measurements in mice that received no cream treatment and were exposed to the same level of SSL, suggesting that the control cream used in these studies did not alter the efficiency of the SSL delivered to mice or the tolerability of mice to SSL. The application of aloe gel creams to mice had no effect on body weights, survival, or the in-life observations of skin lesion onset, incidence, or multiplicity. The administration of aloe gel creams to male mice had no effect on the incidences or multiplicities of histopathology-determined squamous cell nonneoplastic skin lesions or neoplasms. Female mice treated with aloe gel creams (3% and 6%) had significantly increased multiplicities of squamous cell neoplasms. There were no treatment-related effects on body weights, survival, or the in-life observations of skin lesion onset, incidence, or multiplicity in mice treated with the whole leaf creams. In male mice exposed to SSL and treated with the 6% whole leaf cream, a significant increase was observed in the multiplicity of squamous cell neoplasms. Female mice exposed to SSL and treated with the 3% whole leaf creams had significantly decreased multiplicity of squamous cell nonneoplastic lesions and significantly increased multiplicity of squamous cell neoplasms. Female mice exposed to SSL and treated with the 6% whole leaf cream had significantly decreased multiplicity of squamous cell nonneoplastic lesions. The application of decolorized whole leaf creams to mice had no effect on body weights, survival, or the in-life observations of skin lesion onset, incidence, or multiplicity. Male mice administered the 3% decolorized whole leaf cream had significantly increased multiplicity of squamous cell neoplasms. Female mice administered the 3% decolorized whole leaf cream had significantly decreased multiplicity of squamous cell nonneoplastic skin lesions and significantly increased multiplicity of squamous cell neoplasms. In female mice that received the 6% decolorized whole leaf cream, there was a significant increase in the multiplicity of squamous cell neoplasms. As with the Aloe vera plant extracts, the application of aloe-emodin creams to mice had no measurable effect on body weights, survival, or the in-life observations of skin lesion onset, incidence, or multiplicity. The administration of aloe-emodin creams to male mice had no effect on the incidence or multiplicity of histopathology-determined nonneoplastic skin lesions or squamous cell neoplasms. Female mice treated with the 74.6 ug/g aloe-emodin cream had significantly decreased multiplicity of histopathology-determined squamous cell nonneoplastic skin lesions and significantly increased multiplicity of squamous cell neoplasms. CONCLUSIONS: these experiments investigated the potential of topical application of creams containing extracts of Aloe barbadensis Miller plant (aloe gel, whole leaf, or decolorized whole leaf) or aloe-emodin to alter the photocarcinogenic activity of filtered xenon arc simulated solar light (SSL) in male and female SKH-1 hairless mice. Data on skin lesions were collected both on digital images during the in-life phase and by histopathologic evaluation at necropsy. No effects of creams upon SSL-induced skin lesions were identified from data collected during the in-life phase. ALOE GEL OR ALOE-EMODIN: under the conditions of these studies, there was a weak enhancing effect of aloe gel or aloe-emodin on the photocarcinogenic activity of SSL in female but not in male SKH-1 mice based on an increase in the multiplicity of histopathologically determined squamous cell neoplasms. ALOE WHOLE LEAF OR DECOLORIZED WHOLE LEAF: under the conditions of these studies, there was a weak enhancing effect of aloe whole leaf or decolorized whole leaf on the photocarcinogenic activity of SSL in both male and female SKH-1 mice based on an increase in the multiplicity of histopathologically-determined squamous cell neoplasms. PMID- 21031003 TI - Fingolimod (FTY720): discovery and development of an oral drug to treat multiple sclerosis. AB - The discovery of fingolimod (FTY720/Gilenya; Novartis), an orally active immunomodulatory drug, has opened up new approaches to the treatment of multiple sclerosis, the most common inflammatory disorder of the central nervous system. Elucidation of the effects of fingolimod--mediated by the modulation of sphingosine 1-phosphate (S1P) receptors--has indicated that its therapeutic activity could be due to regulation of the migration of selected lymphocyte subsets into the central nervous system and direct effects on neural cells, particularly astrocytes. An improved understanding of the biology of S1P receptors has also been gained. This article describes the discovery and development of fingolimod, which was approved by the US Food and Drug Administration in September 2010 as a first-line treatment for relapsing forms of multiple sclerosis, thereby becoming the first oral disease-modifying therapy to be approved for multiple sclerosis in the United States. PMID- 21031008 TI - Optimizing the pathology workstation "cockpit": Challenges and solutions. AB - The 21(st) century has brought numerous changes to the clinical reading (i.e., image or virtual pathology slide interpretation) environment of pathologists and it will continue to change even more dramatically as information and communication technologies (ICTs) become more widespread in the integrated healthcare enterprise. The extent to which these changes impact the practicing pathologist differ as a function of the technology under consideration, but digital "virtual slides" and the viewing of images on computer monitors instead of glass slides through a microscope clearly represents a significant change in the way that pathologists extract information from these images and render diagnostic decisions. One of the major challenges facing pathologists in this new era is how to best optimize the pathology workstation, the reading environment and the new and varied types of information available in order to ensure efficient and accurate processing of this information. Although workstations can be stand-alone units with images imported via external storage devices, this scenario is becoming less common as pathology departments connect to information highways within their hospitals and to external sites. Picture Archiving and Communications systems are no longer confined to radiology departments but are serving the entire integrated healthcare enterprise, including pathology. In radiology, the workstation is often referred to as the "cockpit" with a "digital dashboard" and the reading room as the "control room." Although pathology has yet to "go digital" to the extent that radiology has, lessons derived from radiology reading "cockpits" can be quite valuable in setting up the digital pathology reading room. In this article, we describe the concept of the digital dashboard and provide some recent examples of informatics-based applications that have been shown to improve the workflow and quality in digital reading environments. PMID- 21031009 TI - Ten important lessons we have learned as pathology bloggers. PMID- 21031010 TI - Tolerance testing of passive radio frequency identification tags for solvent, temperature, and pressure conditions encountered in an anatomic pathology or biorepository setting. AB - BACKGROUND: Radio frequency identification (RFID) tags have potential for use in identifying and tracking biospecimens in anatomic pathology and biorepository laboratories. However, there is little to no data on the tolerance of tags to solutions, solvents, temperatures, and pressures likely to be encountered in the laboratory. The functioning of the Hitachi Mu-chip RFID tag, a candidate for pathology use, was evaluated under such conditions. METHODS: The RFID tags were affixed to cryovials containing tissue or media, glass slides, and tissue cassettes. The tags were interrogated for readability before and after each testing condition or cycle. Individual tags were subjected to only one testing condition but for multiple cycles. Testing conditions were: 1) Ten wet autoclave cycles (121 degrees C, 15 psi); 2) Ten dry autoclave cycles (121 degrees C, 26 psi); 3) Ten tissue processor cycles; 4) Ten hematoxylin and eosin (H&E) staining cycles; 5) Ten antigen retrieval pressure cooker cycles (125 degrees C, 15 psi); 6) 75 degrees C for seven days; 7) 75-59 degrees C day/night cycles for 7 days; 8) -80 degrees C, -150 degrees C, or -196 degrees C for 12 months; 9) Fifty freeze-thaw cycles (-196 degrees C to 22 degrees C). RESULTS: One hundred percent of tags exposed to cold temperatures from -80 to -196 degrees C (80 tags, 1120 successful reads), high temperatures from 52 to 75 degrees C (40 tags, 420 reads), H & E staining (20 tags, 200 reads), pressure cooker antigen retrieval (20 tags, 200 reads), and wet autoclaving (20 tags, 200 reads) functioned well throughout and after testing. Of note, all 20 tested tags tolerated 50 freeze thaw cycles and all 60 tags subjected to sustained freezing temperatures were readable after 1 year. One dry autoclaved tag survived nine cycles but failed after the tenth. The remaining 19 tags were readable after all 10 dry autoclave cycles. One tag failed after the first tissue processing cycle while the remaining 19 tags survived all 10 tissue processing cycles. CONCLUSIONS: In this preliminary study, these RFID tags show a high-degree of tolerance to tested solutions, solvents, temperature, and pressure conditions. However, a measurable failure rate is detectable under some circumstances and redundant identification systems such as barcodes may be required with the deployment of RFID systems. We have delineated testing protocols that may be used as a framework for preliminary assessments of candidate RFID tag tolerance to laboratory conditions. PMID- 21031011 TI - The use of multispectral imaging to distinguish reactive urothelium from neoplastic urothelium. AB - CONTEXT: The interpretation of urothelial atypia in a setting of chronic inflammation and reactive changes can prove difficult with small biopsies. Limited recuts lessen the efficacy of ancillary studies such as CK20, P53 and CD44 in these instances. OBJECTIVE: To evaluate a triple-immunostain with the assistance of multispectral microscopy. DESIGN: Fifty-three bladder biopsies with previous diagnosis of benign/reactive, dysplastic, carcinoma in situ or carcinoma were prepared using a tripleimmunostain cocktail consisting of CK20, P53 and CD44. Three control stains were used for the purpose of creating a spectral library for the Nuance CRI Flex microscopy system. All specimens were interpreted by light microscopy, processed with the Nuance 2.71 software, and CK20 and P53 were scored blinded to the case diagnoses. CD44 was not scored as it proved difficult to interpret in many cases. RESULTS: The results demonstrated that it was possible to separate CK20, P53 and the counterstain that were co-localized in the biopsies. Separation of the stains demonstrated a correlation of p53 and CK20 dual expression in biopsies diagnosed as carcinoma. Low or undetectable levels of expression were seen in biopsies later diagnosed as reactive or benign. CONCLUSION: The combination of multispectral microscopy and multiple immunostain cocktails form a powerful and useful tool for the interpretation of small biopsies with faint or difficult to interpret staining and for cases with limited material such as small-bladder biopsies. PMID- 21031012 TI - Automated ancillary cancer history classification for mesothelioma patients from free-text clinical reports. AB - BACKGROUND: Clinical records are often unstructured, free-text documents that create information extraction challenges and costs. Healthcare delivery and research organizations, such as the National Mesothelioma Virtual Bank, require the aggregation of both structured and unstructured data types. Natural language processing offers techniques for automatically extracting information from unstructured, free-text documents. METHODS: Five hundred and eight history and physical reports from mesothelioma patients were split into development (208) and test sets (300). A reference standard was developed and each report was annotated by experts with regard to the patient's personal history of ancillary cancer and family history of any cancer. The Hx application was developed to process reports, extract relevant features, perform reference resolution and classify them with regard to cancer history. Two methods, Dynamic-Window and ConText, for extracting information were evaluated. Hx's classification responses using each of the two methods were measured against the reference standard. The average Cohen's weighted kappa served as the human benchmark in evaluating the system. RESULTS: Hx had a high overall accuracy, with each method, scoring 96.2%. F measures using the Dynamic-Window and ConText methods were 91.8% and 91.6%, which were comparable to the human benchmark of 92.8%. For the personal history classification, Dynamic-Window scored highest with 89.2% and for the family history classification, ConText scored highest with 97.6%, in which both methods were comparable to the human benchmark of 88.3% and 97.2%, respectively. CONCLUSION: We evaluated an automated application's performance in classifying a mesothelioma patient's personal and family history of cancer from clinical reports. To do so, the Hx application must process reports, identify cancer concepts, distinguish the known mesothelioma from ancillary cancers, recognize negation, perform reference resolution and determine the experiencer. Results indicated that both information extraction methods tested were dependant on the domain-specific lexicon and negation extraction. We showed that the more general method, ConText, performed as well as our task-specific method. Although Dynamic- Window could be modified to retrieve other concepts, ConText is more robust and performs better on inconclusive concepts. Hx could greatly improve and expedite the process of extracting data from free-text, clinical records for a variety of research or healthcare delivery organizations. PMID- 21031013 TI - Design and utilization of the colorectal and pancreatic neoplasm virtual biorepository: An early detection research network initiative. AB - BACKGROUND: The Early Detection Research Network (EDRN) colorectal and pancreatic neoplasm virtual biorepository is a bioinformatics-driven system that provides high-quality clinicopathology-rich information for clinical biospecimens. This NCI-sponsored EDRN resource supports translational cancer research. The information model of this biorepository is based on three components: (a) development of common data elements (CDE), (b) a robust data entry tool and (c) comprehensive data query tools. METHODS: The aim of the EDRN initiative is to develop and sustain a virtual biorepository for support of translational research. High-quality biospecimens were accrued and annotated with pertinent clinical, epidemiologic, molecular and genomic information. A user-friendly annotation tool and query tool was developed for this purpose. The various components of this annotation tool include: CDEs are developed from the College of American Pathologists (CAP) Cancer Checklists and North American Association of Central Cancer Registries (NAACR) standards. The CDEs provides semantic and syntactic interoperability of the data sets by describing them in the form of metadata or data descriptor. The data entry tool is a portable and flexible Oracle-based data entry application, which is an easily mastered, web-based tool. The data query tool facilitates investigators to search deidentified information within the warehouse through a "point and click" interface thus enabling only the selected data elements to be essentially copied into a data mart using a dimensional-modeled structure from the warehouse's relational structure. RESULTS: The EDRN Colorectal and Pancreatic Neoplasm Virtual Biorepository database contains multimodal datasets that are available to investigators via a web-based query tool. At present, the database holds 2,405 cases and 2,068 tumor accessions. The data disclosure is strictly regulated by user's authorization. The high-quality and well-characterized biospecimens have been used in different translational science research projects as well as to further various epidemiologic and genomics studies. CONCLUSIONS: The EDRN Colorectal and Pancreatic Neoplasm Virtual Biorepository with a tangible translational biomedical informatics infrastructure facilitates translational research. The data query tool acts as a central source and provides a mechanism for researchers to efficiently query clinically annotated datasets and biospecimens that are pertinent to their research areas. The tool ensures patient health information protection by disclosing only deidentified data with Institutional Review Board and Health Insurance Portability and Accountability Act protocols. PMID- 21031014 TI - Effects of mycophenolate mofetil on proliferation and mucin-5AC expression in human conjunctival goblet cells in vitro. AB - PURPOSE: To investigate the effects of mycophenolate mofetil (MMF) on proliferation and mucin-5AC (MUC5AC) mRNA expression of normal human conjunctival goblet cells (CGCs) in vitro and to understand mechanisms of MMF in treatment of dry eye syndrome at molecular level. METHODS: Purified human CGCs were treated with a series of graded concentrations of MMF after being confirmed by immunocytochemistry and flow cytometry. Proliferation and MUC5AC mRNA expression of CGCs were measured by Cell Count Kit-8 (CCK-8) and quantitative nested real time reverse transcription polymerase chain reaction (QNRT-PCR at 24 h after treatment. The cell proliferation and MUC5AC mRNA expressiion were compared among different doses of MMF. RESULTS: MMF induced a dose-dependent upregulation of MUC5AC mRNA expression (F=238.851, p<0.01) but a biphase effect on proliferation of the CGCs over 24 h of co-incubation. This biphase effect manifested as a dose dependent increase in cell numbers with MMF from 0.25 to 2.5 ng/ml, an unchanged population of the cells from 2.5 to 10 ng/ml and a reduced population of the cells from 25 to 100 ng/ml. CONCLUSIONS: MMF exerts biphase effects on cell regeneration and upregulates MUC5AC mRNA expression in CGCs in vitro. It appears that the use of MMF at low concentrations is attractive in dry eye (DE) treatment. PMID- 21031015 TI - Aqueous humor hepcidin prohormone levels in patients with primary open angle glaucoma. AB - PURPOSE: This study was designed to evaluate the levels of Interleukin-6 (IL6) and Hepcidin prohormone (Hep) in the serum and aqueous humor of patients with primary open-angle glaucoma (POAG), as well as those with senile cataract as a control group. METHODS: Levels of IL6 and Hep were measured by enzyme-linked immunosorbent assay (ELISA) methods in serum and aqueous humor aspirates taken from 45 patients (POAG=20, Control=25) during anterior segment surgery. RESULTS: The mean aqueous humor Hep concentration in eyes with POAG was significantly higher than that controls (34.55+/-23.01 ng/ml versus 20.82+/- 24.63 ng/ml, p=0.04). There was no significant difference between the serum Hep concentration of POAG and the control group (359.46+/-113.03 ng/ml versus 287.36+/-130.53 ng/ml, p=0.08). There was also no significant difference between either serum (6.18+/-5.22 versus 10.84+/-3.37, pg/ml p=0.112) or aqueous humor (4.39+/-3.06 versus 5.79+/-2.63, pg/ml p=0.14) IL6 concentrations of POAG and the control groups. No significant correlations were found between aqueous humor and serum Hep and IL6 levels in either POAG or the control groups (p>0.05). CONCLUSIONS: The aqueous humor Hep level may exist locally and independent from the IL6 increase in patients with POAG, suggesting that Hep might represent a bridge protein between local inflammation and the consequent loss of retinal ganglion cells. PMID- 21031016 TI - Evaluation of BLID and LOC399959 as candidate genes for high myopia in the Chinese Han population. AB - PURPOSE: BH3-like motif containing, cell death inducer (BLID) and LOC399959 are two genes associated with the single nucleotide polymorphism (SNP) rs577948, which is a susceptibility locus for high myopia in Japanese subjects. The purpose of this study was to determine if BLID and LOC399959 are associated with high myopia in Chinese Han subjects. METHODS: High myopia subjects (n=476) had a spherical refractive error of less than -6.00 D in at least one eye and/or an axial length greater than 26 mm. Genomic DNA was extracted and genotyped from peripheral blood leukocytes of high myopes and controls (n=275). Using a case control association study of candidate regions, linkage disequilibrium blocks for 19 tag SNPs (tSNPs), including rs577948, harbored within and surrounding the BLID and LOC399959 genes were analyzed on a MassArray platform using iPlex chemistry. Each of the tSNPs had an r(2)>0.8 and minor allele frequency >10% in the Chinese Han population. Haplotype association analysis was performed on Haploview 4.1 using Chi-square (chi(2)) tests. RESULTS: None of the 19 tSNPs were statistically associated with high myopia. CONCLUSIONS: While rs577948 may be associated with high myopia in Japanese subjects, it and the other tSNPs near the BLID and LOC399959 genes are not susceptibility loci for high myopia in the Chinese Han population. Thus, associations of SNPs with high myopia as determined by Genome Wide Association Study (GWAS) may be restricted to certain ethnic or genetically distinct populations. Without systematic replication in other populations, the results of GWAS associations should be interpreted with great caution. PMID- 21031017 TI - NK cell depletion delays corneal allograft rejection in baby rats. AB - PURPOSE: Penetrating keratoplasty has a very poor outcome compared with adults if performed in the first years of life. Rejection in these young patients occurs even in the absence of known immunological risk factors. Recently, a baby rat model was introduced and an essential contribution of natural killer (NK) cells during allograft rejection was suggested. To analyze this, NK cells were depleted in baby rats before keratoplasty. METHODS: Allogeneic keratoplasty was performed between Lewis and Fisher rats. The recipient's ages were 10 and 3 weeks, respectively. NK cells were depleted by an intraperitoneal injection of a monoclonal antibody. All experiments were controlled by the injection of isotypic control antibodies and syngeneically. Survival rates were calculated and cellular infiltrates were analyzed histologically. RESULTS: NK cell depletion did delay median graft survival times in a statistically significantly way compared with the control animals (p<0.01). At median rejection time points, macrophages, CD4(+) T cells and CD25(+) leukocytes infiltrated to a greater extent in the depleted recipients. No significant changes in the cell numbers of infiltrating CD8(+) T cells were observed. CONCLUSIONS: We conclude that NK cells play a role during allograft rejection in baby rats, but their effect is replaceable. A greater infiltration of macrophages and CD4(+) T cells suggests that they might compensate for the missing NK cells' response in this experimental setting. Our results represent another step toward understanding the complex mechanisms of an accelerated corneal graft rejection in infant recipients. PMID- 21031018 TI - Localization of the paranodal protein Caspr in the mammalian retina. AB - PURPOSE: The retina has the demanding task of encoding all aspects of the visual scene within the space of one fixation period lasting only a few hundred milliseconds. To accomplish this feat, information is encoded in specialized parallel channels and passed on to numerous central nuclei via the optic nerve. These parallel channels achieve specialization in at least three ways: the synaptic networks in which they participate, the neurotransmitter receptors expressed and the types and locations of ion channels or transporters used. Subcellular localization of receptors, channels and transporters is made yet more complex in the retina by the double duty many retinal processes serve. In the present work, we show that the protein Caspr (Contactin Associated Protein), best known for its critical role in the localization of voltage-gated ion channels at the nodes of Ranvier, is present in several types of retinal neurons including amacrine, bipolar, horizontal, and ganglion cells. METHODS: Using standard double label immunofluorescence protocols, we characterized the pattern of Caspr expression in the rodent retina. RESULTS: Caspr labeling was observed through much of the retina, including horizontal, bipolar, amacrine, and ganglion cells. Among amacrine cells, Caspr was observed in AII amacrine cells through co localization with Parvalbumin and Disabled-1 in rat and mouse retinas, respectively. An additional amacrine cell type containing Calretinin also co localized with Caspr, but did not co-localize with choline-acetyltransferase. Nearly all cells in the ganglion cell layer contain Caspr, including both displaced amacrine and ganglion cells. In the outer retina, Caspr was co localized with PKC labeling in rod bipolar cell dendrites. In addition, Caspr labeling was found inside syntaxin-4 'sandwiches' in the outer plexiform layer, most likely indicating its presence in cone bipolar cell dendrites. Finally, Caspr was co-localized in segments of horizontal cell dendrites labeled with Calbindin-D28k. CONCLUSIONS: Caspr is best known for its role in organizing the localization of different voltage-gated ion channels in and around nodes of Ranvier. As neuronal processes in the retina often play a dual role involving both input and output, it is possible that the localization of Caspr in the retina will help us decipher the way retinal cells localize ion channels in their processes to increase computational capacity. PMID- 21031019 TI - LOC387715/HTRA1 gene polymorphisms and susceptibility to age-related macular degeneration: A HuGE review and meta-analysis. AB - PURPOSE: To examine the association of age-related macular degeneration (AMD) with HtrA serine peptidase 1 (HTRA1) gene rs11200638 G->A polymorphism and LOC387715/ ARMS2 gene rs10490924 G->T polymorphisms, and to evaluate the magnitude of the gene effect and the possible genetic mode of action. METHODS: We searched the US National Library of Medicine's PubMed, Embase, OMIM, ISI Web of Science, and CNKI databases in a systematic manner to retrieve all genetic association studies on the HTRA1 (rs11200638) and LOC387715/ ARMS2 (rs10490924) gene polymorphisms and AMD. We performed a meta-analysis conducted with Stata software, version 9.0. RESULTS: Individuals who carried the AA and AG genotypes of HTRA1 gene rs11200638 G->A polymorphism had 2.243 and 8.669 times the risk of developing AMD, respectively, when compared with those who carry the GG genotype. Individuals carrying the TT and TG genotypes of LOC387715/ ARMS2 gene rs10490924 G->T polymorphism had 7.512 and 2.353 times the risk of developing AMD, respectively, compared with those who carry GG genotype. These results suggested a "moderate" codominant, multiplicative genetic mode; that is, both HTRA1 rs11200638 G->A polymorphism and LOC387715/ARMS2 rs10490924 G->T polymorphism play important roles in the pathogenesis of AMD. We found no evidence of publication bias. Between-study heterogeneity was found in both allele-based analysis and genotype-based analysis. CONCLUSIONS: HTRA1 rs11200638 G->A polymorphism and LOC387715/ARMS2 rs10490924 G->T polymorphism play important roles in AMD. Gene-gene and gene-environmental interactions, as well as precise mechanisms underlying common variants in the HTRA1 gene and LOC387715/ ARMS2 gene, potentially increase the risk of AMD and need further exploration. PMID- 21031020 TI - Subtoxic levels hydrogen peroxide-induced production of interleukin-6 by retinal pigment epithelial cells. AB - PURPOSE: To study the effect of subtoxic levels of hydrogen peroxide (H(2)O(2)) on the expression and release of interleukin-6 (IL-6) by cultured retinal pigment epithelial (RPE) cells and to explore the relevant signal pathways. METHODS: Cultured human RPE cells were stimulated with various subtoxic concentrations of H(2)O(2) for different periods. Conditioned medium and cells were collected. IL-6 in the medium and IL-6 mRNA in the collected cells were measured using an IL-6 enzyme-linked immunosorbent assay kit and reverse transcriptase polymerase chain reaction, respectively. Nuclear factor-kappaB (NF-kappaB) in nuclear extracts and phosphorylated p38 mitogen-activated protein kinase (MAPK), extracellular signal regulated kinase (ERK), and c-Jun N-terminal kinases (JNK) in cells cultured with and without H(2)O(2) were measured by NF-kappaB and MAPK enzyme-linked immunosorbent assay kits. Inhibitors of p38 (SB203580), ERK (UO1026), JNK (SP600125), and NF-kappaB (BAY11-7082) were added to the cultures before the addition of H(2)O(2) to test their effects(.) RESULTS: Subtoxic levels of H(2)O(2) (100 uM and less) increased the IL-6 mRNA level and the release of IL-6 protein by the cultured human RPE cells in a dose- and time-dependent manner. This was accompanied by an increase of NF-kappaB in nuclear extracts and phosphorylated p38 MAPK, ERK, and JNK in cell lysates, particularly in the p38 and NF-kappaB. The NF-kappaB inhibitor decreased the H(2)O(2)-induced expression of IL-6. The p38 inhibitor, but not the ERK or JNK inhibitor, completely abolished H(2)O(2)-induced expression of IL-6 by RPE cells. The p38 inhibitor also abolished the increase of NF-kappaB in nuclear extracts in cells treated with H(2)O(2). CONCLUSIONS: H(2)O(2) stimulated the production of IL-6, a key factor in the modulation of immune responses, inflammatory processes, and the occurrence of autoimmune diseases, which recently has been documented to be increased in age-related macular degeneration (AMD). This may be a molecular linkage for the oxidative stress and inflammatory/autoimmune reactions in AMD and may provide a novel target for the treatment of AMD. PMID- 21031022 TI - Bevacizumab neutralizes the protective effect of vascular endothelial growth factor on retinal ganglion cells. AB - PURPOSE: Vascular endothelial growth factor (VEGF) is well known for its role in pathologic neovascularization, including wet age-related macular degeneration. However, a growing body of evidence indicates that VEGF is also neuroprotective of non-vascular cells in various animal models through reduction of oxidative stress. In light of the widespread use of intraocular anti-VEGF therapies for age related macular degeneration (AMD), we evaluated the impact of anti-VEGF agents on the neuroprotective effect of VEGF on retinal ganglion cells. METHODS: Staurosporine differentiated retinal ganglion cells were treated with increasing doses of VEGF in the presence of hydrogen peroxide. After optimization, an increasing concentration of bevacizumab was added to neutralize VEGF-mediated protection. The degree of oxidative damage was measured at various time points using buthionine sulfoxime (BSO), a glutathione reductase inhibitor. Cell viability was assessed using WST-1 and Crystal violet assays. RESULTS: VEGF (200 ng/ml) protected differentiated retinal ganglion cells (RGC)-5 against H(2)0(2) mediated oxidative stress. This effect was eliminated by co-treatment with bevacizumab (2.0 mg/ml), which by itself was not cytotoxic. CONCLUSIONS: These results indicate an important role for VEGF in the maintenance of retinal ganglion cells. PMID- 21031021 TI - Molecular analysis of cataract families in India: new mutations in the CRYBB2 and GJA3 genes and rare polymorphisms. AB - PURPOSE: The aim of the study was to resolve the genetic etiology in families having inherited cataracts. METHODS: Families afflicted with congenital/childhood cataracts were registered in Chennai and Orissa (India). Blood samples were collected from the probands and available family members. Selected functional candidate genes were amplified by polymerase chain reaction (PCR) and characterized by direct sequencing. Putative mutations were confirmed in healthy controls. RESULTS: We observed interesting new polymorphisms of ethnic specificity, some of frequent nature, such as a 3-bp deletion in intron 3 of CRYBB2 (encoding betaB2-crystallin) and IVS1+9 c>t variation in HSF4 (encoding heat-shock factor 4). Some rare single nucleotide polymorphisms (SNPs) co segregate with the respective phenotype such as IVS3+120c>a of CRYBB2, while M44V of CRYGD (encoding gammaD-crystallin), although found in association with blue dot opacity was seen in a few healthy controls too. We identified two new mutations co-segregating along with the respective cataract phenotype within the families that were not seen in healthy controls from India or Germany. These include two missense mutations; one in GJA3 (encoding gap junction protein alpha3, which is also referred to as connexin 46); the mutation affects codon 19 (T19M), and the corresponding phenotype is a posterior-polar cataract. The other missense mutation affects CRYBB2 (W59C; total cataract). Additionally, a cDNA variation (G54A) identified in a zonular cataract affects a highly conserved splice site of CRYBB2. This mutation, however, showed reduced penetrance in the family, which might be explained by different molecular consequences in the affected family members: nonsense-mediated decay of the mutated mRNA might have no clinical phenotype in heterozygotes, whereas the translation of the mutated mRNA is predicted to lead to a small hybrid protein (consisting of 16 amino acids of the betaB2-crystallin and 18 new amino-acids), which might have a dominant negative function in the lens. CONCLUSIONS: This report identifies in families with childhood cataract some new alleles, which may be considered as causative for cataracts. Furthermore, we report some geographically restricted rare polymorphic sites, whose significance might be considered in some context as modifiers or alleles in sensitizing ocular lens toward cataractogenesis. PMID- 21031023 TI - Tear proteomics in keratoconus. AB - PURPOSE: The purpose of this work was to identify potential tear-film based proteins expressed in keratoconus. METHODS: Recruited subjects were normal gas permeable (GP) contact lens wearers, keratoconus subjects wearing GP contact lenses, and keratoconus subjects without contact lenses. Subjects wearing soft lenses or having previous ocular surgeries were excluded from participating. Approximately 5 ul of tears were sampled from both eye of each subject using glass microcapillaries. Additional testing included a brief history, visual acuity, slit lamp examination, and topography. Proteomic analyses used to compare samples included Bradford assays, cytokine arrays, SDS-PAGE, and mass spectrometry. RESULTS: Forty-four subjects were enrolled in the study including 20 normals (GP wearers), 18 with keratoconus and wearing GPs, and six with keratoconus (non-lens wearers). Across all proteomic approaches, several proteins were identified as possibly being unique to keratoconus. Increased expression of matrix metalloproteinase-1 (MMP-1) was found in keratoconus subjects with and without gas permeable contact lenses (p=0.02). Unique proteins more associated with keratoconus included several keratins, immunoglobulins alpha and kappa, precursors to prolactin, lysozyme C, and lipocalin. CONCLUSIONS: Initial analyses indicate that keratoconus may be associated with the differential expression of several proteins. Further testing is needed to determine any causal relationship or correlation with the etiology of this condition. PMID- 21031024 TI - A novel antiangiogenic peptide derived from hepatocyte growth factor inhibits neovascularization in vitro and in vivo. AB - PURPOSE: To study the antiangiogenic activity of two small peptides (H-RN and H FT) derived from the hepatocyte growth factor kringle 1 domain (HGF K1) using in vitro and in vivo assays. METHODS: RF/6A rhesus macaque choroid-retina endothelial cells were used for in vitro studies. The inhibiting effect of two peptides on a vascular endothelial growth factor (VEGF)-stimulated cell proliferation, cell migration, and endothelial cell tube formation were investigated. For in vivo assays, the antiangiogenic activity of H-RN and H-FT in the chick chorioallantoic membrane model (CAM) and a mice oxygen-induced retinopathy model (OIR) were studied. A recombinant mouse VEGF-neutralizing antibody, bevacizumab, and a scrambled peptide were used as two control groups in separate studies. RESULTS: H-RN effectively inhibited VEGF-stimulated RF/6A cell proliferation, migration, and tube formation on MatrigelTM, while H-FT did not. H RN was also able to inhibit angiogenesis when applied to the CAM, and had antineovascularization activity in the retinal neovascularization of a mouse OIR model when administrated as an intravitreous injection. The antiangiogenic activity of H-RN was not as strong as that of VEGF antibodies. The H-FT and scrambled peptide had no such activity. CONCLUSIONS: H-RN, a new peptide derived from the HGF K1 domain, was shown to have antiangiogenic activity in vitro and in vivo. It may lead to new potential drug discoveries and the development of new treatments for pathological retinal angiogenesis. PMID- 21031026 TI - MYOC and FOXC1 gene analysis in primary congenital glaucoma. AB - PURPOSE: To screen the myocilin (MYOC) and forkhead box protein C1 (FOXC1) genes for sequence variations in primary congenital glaucoma (PCG). METHODS: Seventy five PCG patients were screened for MYOC variations and 54 cases (negative or heterozygous for cytochrome P4501B1 mutations) for FOXC1 mutations by polymerase chain reaction (PCR) and DNA sequencing. RESULTS: Five single nucleotide polymorphisms (SNPs; -126T>C, -83G>A, p.R76K, IVS2+35G>A, and p.Y347Y) were identified in MYOC and two sequence variations (GGC375ins and GGC447ins) in FOXC1. No pathogenic variations were identified in MYOC and FOXC1 in our patients. CONCLUSIONS: MYOC and FOXC1 mutations are not involved in pathogenesis of primary congenital glaucoma in our patients. Thus, it is important to screen other loci for involvement in congenital glaucoma in cases which are negative or heterozygous for CYP1B1 mutations to have a better insight in to disease pathogenesis. PMID- 21031025 TI - Genotyping HLA-DRB1 and HLA-DQB1 alleles in Japanese patients with normal tension glaucoma. AB - PURPOSE: Normal tension glaucoma (NTG) is a subtype of glaucoma in which intraocular pressure is within the statistically normal range. NTG may be associated with an immune disorder. The aim of this study was to determine whether specific alleles in the human leukocyte antigen (HLA)-DRB1 and HLA-DQB1 genes correlated with NTG in Japanese patients. METHODS: We genotyped the HLA DRB1 and HLA-DQB1 alleles in 113 Japanese patients with NTG and in 184 healthy Japanese control subjects using the polymerase chain reaction-sequence-specific oligonucleotide probes (PCR-SSOP) Luminex method. We assessed the allelic diversity in patients and controls. RESULTS: There were no statistically significant differences in the allele frequency of HLADRB1 and HLA-DQB1 between NTG patients and control subjects, and no HLA-DRB1-HLA-DQB1 haplotypes demonstrated any significant association with NTG. CONCLUSIONS: Our findings suggest that HLA-DRB1 and HLA-DQB1 polymorphisms have no significant effect on the development of NTG in Japanese patients. PMID- 21031027 TI - Compensating Inhomogeneities of Neuromorphic VLSI Devices Via Short-Term Synaptic Plasticity. AB - Recent developments in neuromorphic hardware engineering make mixed-signal VLSI neural network models promising candidates for neuroscientific research tools and massively parallel computing devices, especially for tasks which exhaust the computing power of software simulations. Still, like all analog hardware systems, neuromorphic models suffer from a constricted configurability and production related fluctuations of device characteristics. Since also future systems, involving ever-smaller structures, will inevitably exhibit such inhomogeneities on the unit level, self-regulation properties become a crucial requirement for their successful operation. By applying a cortically inspired self-adjusting network architecture, we show that the activity of generic spiking neural networks emulated on a neuromorphic hardware system can be kept within a biologically realistic firing regime and gain a remarkable robustness against transistor-level variations. As a first approach of this kind in engineering practice, the short-term synaptic depression and facilitation mechanisms implemented within an analog VLSI model of I&F neurons are functionally utilized for the purpose of network level stabilization. We present experimental data acquired both from the hardware model and from comparative software simulations which prove the applicability of the employed paradigm to neuromorphic VLSI devices. PMID- 21031028 TI - Burrowing behavior as an indicator of post-laparotomy pain in mice. AB - Detection of persistent pain of a mild-to-moderate degree in laboratory mice is difficult because mice do not show unambiguous symptoms of pain or suffering using standard methods of short-term observational or clinical monitoring. This study investigated the potential use of burrowing performance - a spontaneous and highly motivated behavior - as a measure of post-operative pain in laboratory mice. The influence of minor surgery on burrowing was investigated in adult C57BL/6J mice of both genders in a modified rodent burrowing test (displacement of food pellets from a pellet-filled tube) within the animal's home cage. Almost all (98%) healthy mice burrowed (mean latency 1.3 h, SEM 0.5 h). After surgery without pain treatment, latency of burrowing was significantly prolonged (mean Delta latency 10 h). Analgesic treatment using the anti-inflammatory drug carprofen (5 mg/kg bodyweight) decreased latency of burrowing after surgery (mean Delta latency 5.5 h) to the level found in mice that had been anesthetized (mean Delta latency 5.4 h) or had received anesthesia and analgesia (mean Delta latency 4.6 h). Analgesia during surgery was associated with a significantly earlier onset of burrowing compared to surgery without pain treatment. A distinct gradation in burrowing performance was found ranging from the undisturbed pre operative status to the intermediate level following anesthesia/analgesia and surgery with analgesia, to the pronounced prolongation of latency to burrow after surgery without pain relief. In conclusion, post-surgical impairment of general condition, probably mainly attributable to pain, can be conveniently assessed in laboratory mice on the basis of the burrowing test. PMID- 21031029 TI - Demixing population activity in higher cortical areas. AB - Neural responses in higher cortical areas often display a baffling complexity. In animals performing behavioral tasks, single neurons will typically encode several parameters simultaneously, such as stimuli, rewards, decisions, etc. When dealing with this large heterogeneity of responses, cells are conventionally classified into separate response categories using various statistical tools. However, this classical approach usually fails to account for the distributed nature of representations in higher cortical areas. Alternatively, principal component analysis (PCA) or related techniques can be employed to reduce the complexity of a data set while retaining the distributional aspect of the population activity. These methods, however, fail to explicitly extract the task parameters from the neural responses. Here we suggest a coordinate transformation that seeks to ameliorate these problems by combining the advantages of both methods. Our basic insight is that variance in neural firing rates can have different origins (such as changes in a stimulus, a reward, or the passage of time), and that, instead of lumping them together, as PCA does, we need to treat these sources separately. We present a method that seeks an orthogonal coordinate transformation such that the variance captured from different sources falls into orthogonal subspaces and is maximized within these subspaces. Using simulated examples, we show how this approach can be used to demix heterogeneous neural responses. Our method may help to lift the fog of response heterogeneity in higher cortical areas. PMID- 21031030 TI - Disrupted modularity and local connectivity of brain functional networks in childhood-onset schizophrenia. AB - Modularity is a fundamental concept in systems neuroscience, referring to the formation of local cliques or modules of densely intra-connected nodes that are sparsely inter-connected with nodes in other modules. Topological modularity of brain functional networks can quantify theoretically anticipated abnormality of brain network community structure - so-called dysmodularity - in developmental disorders such as childhood-onset schizophrenia (COS). We used graph theory to investigate topology of networks derived from resting-state fMRI data on 13 COS patients and 19 healthy volunteers. We measured functional connectivity between each pair of 100 regional nodes, focusing on wavelet correlation in the frequency interval 0.05-0.1 Hz, then applied global and local thresholding rules to construct graphs from each individual association matrix over the full range of possible connection densities. We show how local thresholding based on the minimum spanning tree facilitates group comparisons of networks by forcing the connectedness of sparse graphs. Threshold-dependent graph theoretical results are compatible with the results of a k-means unsupervised learning algorithm and a multi-resolution (spin glass) approach to modularity, both of which also find community structure but do not require thresholding of the association matrix. In general modularity of brain functional networks was significantly reduced in COS, due to a relatively reduced density of intra-modular connections between neighboring regions. Other network measures of local organization such as clustering were also decreased, while complementary measures of global efficiency and robustness were increased, in the COS group. The group differences in complex network properties were mirrored by differences in simpler statistical properties of the data, such as the variability of the global time series and the internal homogeneity of the time series within anatomical regions of interest. PMID- 21031031 TI - A general and efficient method for incorporating precise spike times in globally time-driven simulations. AB - Traditionally, event-driven simulations have been limited to the very restricted class of neuronal models for which the timing of future spikes can be expressed in closed form. Recently, the class of models that is amenable to event-driven simulation has been extended by the development of techniques to accurately calculate firing times for some integrate-and-fire neuron models that do not enable the prediction of future spikes in closed form. The motivation of this development is the general perception that time-driven simulations are imprecise. Here, we demonstrate that a globally time-driven scheme can calculate firing times that cannot be discriminated from those calculated by an event-driven implementation of the same model; moreover, the time-driven scheme incurs lower computational costs. The key insight is that time-driven methods are based on identifying a threshold crossing in the recent past, which can be implemented by a much simpler algorithm than the techniques for predicting future threshold crossings that are necessary for event-driven approaches. As run time is dominated by the cost of the operations performed at each incoming spike, which includes spike prediction in the case of event-driven simulation and retrospective detection in the case of time-driven simulation, the simple time driven algorithm outperforms the event-driven approaches. Additionally, our method is generally applicable to all commonly used integrate-and-fire neuronal models; we show that a non-linear model employing a standard adaptive solver can reproduce a reference spike train with a high degree of precision. PMID- 21031032 TI - Response time distributions in rapid chess: a large-scale decision making experiment. AB - Rapid chess provides an unparalleled laboratory to understand decision making in a natural environment. In a chess game, players choose consecutively around 40 moves in a finite time budget. The goodness of each choice can be determined quantitatively since current chess algorithms estimate precisely the value of a position. Web-based chess produces vast amounts of data, millions of decisions per day, incommensurable with traditional psychological experiments. We generated a database of response times (RTs) and position value in rapid chess games. We measured robust emergent statistical observables: (1) RT distributions are long tailed and show qualitatively distinct forms at different stages of the game, (2) RT of successive moves are highly correlated both for intra- and inter-player moves. These findings have theoretical implications since they deny two basic assumptions of sequential decision making algorithms: RTs are not stationary and can not be generated by a state-function. Our results also have practical implications. First, we characterized the capacity of blunders and score fluctuations to predict a player strength, which is yet an open problem in chess softwares. Second, we show that the winning likelihood can be reliably estimated from a weighted combination of remaining times and position evaluation. PMID- 21031034 TI - Yawning and stretching predict brain temperature changes in rats: support for the thermoregulatory hypothesis. AB - Recent research suggests that yawning is an adaptive behavior that functions to promote brain thermoregulation among homeotherms. To explore the relationship between brain temperature and yawning we implanted thermocoupled probes in the frontal cortex of rats to measure brain temperature before, during and after yawning. Temperature recordings indicate that yawns and stretches occurred during increases in brain temperature, with brain temperatures being restored to baseline following the execution of each of these behaviors. The circulatory changes that accompany yawning and stretching may explain some of the thermal similarities surrounding these events. These results suggest that yawning and stretching may serve to maintain brain thermal homeostasis. PMID- 21031033 TI - Reversible Inactivation of Rat Premotor Cortex Impairs Temporal Preparation, but not Inhibitory Control, During Simple Reaction-Time Performance. AB - Previous studies by our lab and others have established a role for medial areas of the prefrontal cortex (mPFC) in the top-down control of action during simple reaction-time (RT) tasks. However, the neural circuits that allow mPFC to influence activity in the motor system have remained unclear. In the present study, we used a combination of tract-tracing and reversible inactivation methods to examine the role of a motor-related area in the rat frontal cortex, called the rostral forelimb area (RFA), in the top-down control of action. Neural tracing studies involved used electrical microstimulation to identify RFA and injections of biotinylated dextran amines (BDA) to map out connections of RFA with other parts of the frontal cortex. Connections were found between RFA and mPFC, the agranular insular cortex, and the primary motor cortex. Reversible inactivations using muscimol infusions into RFA increased response times and eliminated delay dependent speeding, but did not increase premature responding. These results are markedly different from what is obtained when muscimol is infused into mPFC, which leads to excessive premature responding and a reduction of RTs to stimuli at short delays (Narayanan et al., 2006). We also tested animals during the RT task after inactivating the agranular insular cortex, which contains neurons that projects to and receives from RFA and mPFC, and found no effects on RT performance. Together, these studies suggest that RFA is a premotor region in the rat frontal cortex that competes with mPFC to control action selection. We suggest that RFA controls the threshold that is used to initiate responding and generates prepotent excitation over responding that is crucial for temporal preparation. PMID- 21031037 TI - Emergency medicine in Paarl, South Africa: a cross-sectional descriptive study. AB - BACKGROUND: Emergency Medicine (EM) in South Africa is in its earliest stages of development. There is a paucity of data about emergency department (ED) patient demographics, epidemiology, consultation and admission criteria and other characteristics. AIMS: This information is absolutely necessary to properly guide the development of EM and appropriate emergency care systems. In order to provide this information, we performed a study in a rural hospital in Paarl, 60 km outside Cape Town. METHODS: All patients who were seen in the ED between 1 January 2008 and 31 May 2008 were eligible for our research. We designed a cross sectional descriptive study and retrieved information from a randomized sample of all consecutive patient charts seen during this period using a 40-point questionnaire (see Appendix 1). RESULTS: We investigated 2,446 charts, of which 2,134 were suitable for our research The majority (88.2%) of these patients were self-referred. In our sample, 24.1% were children under 12 years old. Almost 20% of patients had a serious pathological condition or were physiologically unstable; 36.0% of all presentations were trauma related. Besides trauma-related problems, gastrointestinal- (21.9%) and respiratory tract- (12.4%) related problems were most common in the ED; 16.5% of the patients were admitted to a ward. CONCLUSION: This descriptive epidemiological study provides necessary data that will be used for further needs assessments and for future EM development in Paarl, and can be used as a template in other EDs and hospitals to provide similar data necessary for initial EM development strategy. PMID- 21031038 TI - Alcohol-related emergency department attendances: is preloading a risk factor? Cross-sectional survey. AB - INTRODUCTION: 'Preloading' is a phenomenon where people drink alcohol at a private residence before going out. We aimed to identify whether preloading is a risk factor for alcohol-related emergency department attendance. We also wanted to identify where people became injured or unwell. METHODS: We conducted a cross sectional, anonymous, survey at peak drinking times in our emergency department. We interviewed adult patients who presented to our emergency department with an alcohol-related presentation over an 8-week period. RESULTS: We approached 1,079 patients. One hundred sixty-one had suffered an alcohol-related problem while out drinking; 27% of women and 14% of men had their first drink at home. There was no particular presentation or age group that was associated with preloading. Seventy percent of patients stated that they had drunk most of their alcohol at a public place; 76% of patients suffered their alcohol-related problem at a site different from where they had drunk most of their alcohol or where they had had their first drink. CONCLUSION: Preloading is more common in women than men. Preloading is common in alcohol-related emergency department attendances. The proportions of patients preloading in this study are lower than in other studies conducted in different environments. Preloading is not a risk factor for alcohol-related emergency department attendance. Polices to reduce alcohol-related harm should continue to focus on bars, nightclubs and pubs. PMID- 21031036 TI - A network perspective on metabolism and aging. AB - Aging affects a myriad of genetic, biochemical, and metabolic processes, and efforts to understand the underlying molecular basis of aging are often thwarted by the complexity of the aging process. By taking a systems biology approach, network analysis is well-suited to study the decline in function with age. Network analysis has already been utilized in describing other complex processes such as development, evolution, and robustness. Networks of gene expression and protein-protein interaction have provided valuable insight into the loss of connectivity and network structure throughout lifespan. Here, we advocate the use of metabolic networks to expand the work from genomics and proteomics. As metabolism is the final fingerprint of functionality and has been implicated in multiple theories of aging, metabolomic methods combined with metabolite network analyses should pave the way to investigate how relationships of metabolites change with age and how these interactions affect phenotype and function of the aging individual. The metabolomic network approaches highlighted in this review are fundamental for an understanding of systematic declines and of failure to function with age. PMID- 21031035 TI - Nrf2, a guardian of healthspan and gatekeeper of species longevity. AB - Although aging is a ubiquitous process that prevails in all organisms, the mechanisms governing both the rate of decline in functionality and the age of onset remain elusive. A profound constitutively upregulated cytoprotective response is commonly observed in naturally long-lived species and experimental models of extensions to lifespan (e.g., genetically-altered and/or experimentally manipulated organisms), as indicated by enhanced resistance to stress and upregulated downstream components of the cytoprotective nuclear factor erythroid 2-related factor 2 (Nrf2)-signaling pathway. The transcription factor Nrf2 is constitutively expressed in all tissues, although levels may vary among organs, with the key detoxification organs (kidney and liver) exhibiting highest levels. Nrf2 may be further induced by cellular stressors including endogenous reactive oxygen species or exogenous electrophiles. The Nrf2-signaling pathway mediates multiple avenues of cytoprotection by activating the transcription of more than 200 genes that are crucial in the metabolism of drugs and toxins, protection against oxidative stress and inflammation, as well as playing an integral role in stability of proteins and in the removal of damaged proteins via proteasomal degradation or autophagy. Nrf2 interacts with other important cell regulators such as tumor suppressor protein 53 (p53) and nuclear factor-kappa beta (NF kappaB) and through their combined interactions is the guardian of healthspan, protecting against many age-related diseases including cancer and neurodegeneration. We hypothesize that this signaling pathway plays a critical role in the determination of species longevity and that this pathway may indeed be the master regulator of the aging process. PMID- 21031039 TI - The epidemiology of childhood injury in Maputo, Mozambique. AB - BACKGROUND: Injury remains a major cause of death and disability worldwide. AIMS: This study describes the characteristics of childhood injury at three hospitals in Maputo, Mozambique. METHODS: An observational, prospective convenience study was conducted in June and July 2007. We prospectively collected data on 335 children (0-14 years) who presented to three hospitals in Maputo during the study period. RESULTS: The prevalence of trauma-related complaints on presentation to the hospital in this study was 12%, with higher rates in boys (59%) and in those between the ages of 5-9 years (34.9%). Falls were the most common mechanism of injury (40.6%), followed by burns (19.1%) and road traffic injuries (RTI) (14.3%). The majority of falls occurred in the home (61.8%) and were unintentional. (94.1%) Burns were predominantly due to hot liquids (82.8%) and less frequently due to fire (17.2%). The majority of burns involved the patient alone (62.5%). The majority of RTIs were pedestrians struck by vehicles (81.2%). A substantial number of patients presented more than 24 h after injury (23.3%). Children from households living with a lower family income in general suffered trauma more often regardless of the mechanism. CONCLUSIONS: Childhood injury accounts for a substantial burden of disease in Maputo, Mozambique. This study highlights the fact that many of these injuries are consistent with the injury patterns seen in children in other low and middle income countries, and are amenable to prevention, access, and emergency care programs targeted at children and their families, schools, and the local and national community. PMID- 21031041 TI - Use of an improvised pneumatic anti-shock garment and a non-pneumatic anti-shock garment to control pelvic blood flow. AB - BACKGROUND: Pelvic bleeding from trauma and postpartum hemorrhage is often difficult to treat successfully by emergency providers particularly in low resource environments, when hospital presentation is delayed or there is a lack of immediate surgical, anesthesia, and transfusion capabilities. Pneumatic anti shock garments (PASG) decrease pelvic blood flow and hemorrhage. A tightly fitted neoprene non-pneumatic anti-shock garment (NASG) has been shown to decrease blood loss and improve survival rates from postpartum hemorrhage. AIMS: The objective of this study was to determine whether blood flow to the pelvis is decreased by use of the NASG or by an improvised PASG. METHODS: A PASG was made using three bicycle tubes, placing one tube on each leg and one on the lower abdomen/pelvis, wrapping firmly with sheets and inflating the tubes to approximately 3.5 bar (45 psi). A Doppler ultrasound was used to measure distal aortic blood flow in 12 healthy adults at baseline and in both devices. Data were analyzed with one sample and paired t tests. RESULTS: Mean flow was 1.99 l/min at baseline. Mean flow decrease was 1.11 [95% confidence interval (CI): 0.64-1.57, p = 0.0003 for the difference] for the PASG and 0.65 (95% CI: 0.03-1.26, p = 0.04) for the NASG. The PASG decreased blood flow more than the NASG (mean difference: 0.46, 95% CI: 0.02-0.90, p = 0.04). CONCLUSIONS: Both devices decreased distal aortic blood flow, but the improvised PASG device decreased it by a larger margin. PMID- 21031040 TI - Epidemiology of injuries presenting to the national hospital in Kampala, Uganda: implications for research and policy. AB - BACKGROUND: Despite the growing burden of injuries in LMICs, there are still limited primary epidemiologic data to guide health policy and health system development. Understanding the epidemiology of injury in developing countries can help identify risk factors for injury and target interventions for prevention and treatment to decrease disability and mortality. AIM: To estimate the epidemiology of the injury seen in patients presenting to the government hospital in Kampala, the capital city of Uganda. METHODS: A secondary analysis of a prospectively collected database collected by the Injury Control Centre-Uganda at the Mulago National Referral Hospital, Kampala, Uganda, 2004-2005. RESULTS: From 1 August 2004 to 12 August 2005, a total of 3,750 injury-related visits were recorded; a final sample of 3,481 records were analyzed. The majority of patients (62%) were treated in the casualty department and then discharged; 38% were admitted. Road traffic injuries (RTIs) were the most common causes of injury for all age groups in this sample, except for those under 5 years old, and accounted for 49% of total injuries. RTIs were also the most common cause of mortality in trauma patients. Within traffic injuries, more passengers (44%) and pedestrians (30%) were injured than drivers (27%). Other causes of trauma included blunt/penetrating injuries (25% of injuries) and falls (10%). Less than 5% of all patients arriving to the emergency department for injuries arrived by ambulance. CONCLUSIONS: Road traffic injuries are by far the largest cause of both morbidity and mortality in Kampala. They are the most common cause of injury for all ages, except those younger than 5, and school-aged children comprise a large proportion of victims from these incidents. The integration of injury control programs with ongoing health initiatives is an urgent priority for health and development. PMID- 21031042 TI - Successful treatment of a severely injured soldier from Afghanistan with pumpless extracorporeal lung assist and neurally adjusted ventilatory support. AB - BACKGROUND: Life-threatening acute lung injury due to combat and/or terror attacks is associated with high mortality. The successful management includes the use of "rescue" extracorporeal lung assist and early transport by aeromedical evacuation teams. AIMS: Description of the pre-hospital support of a severely injured soldier with a pumpless extracorporeal arterio-venous lung assist in critical hypercapnia/hypoxemia. METHOD: A British soldier suffered from severe gunshot injuries to the chest and abdomen in Afghanistan. After traumatic pneumonectomy, he developed critical hypercapnia/hypoxemia. He was mechanically ventilated and supported with a pumpless interventional extracorporeal lung assist (iLA, Novalung, Talheim, Germany) and transferred to Germany. RESULTS: A sufficient CO(2) extraction and improvement in oxygenation enabled the safe transportation and lung protective ventilation. Weaning from mechanical ventilation was promoted by the application of a new neurally adjusted ventilatory assist (NAVA). The patient recovered, and he left Germany in stable condition. CONCLUSION: Novel techniques in extracorporeal lung assist and in ventilatory support may help save lives even in disaster medicine. PMID- 21031043 TI - Health information technology in US emergency departments. AB - BACKGROUND: Information technology may improve patient safety, and is a focus of health care reform. A minority of emergency departments (EDs) in Massachusetts, and in academic EDs throughout the US, have electronic health records. AIMS: Assess health information technology adoption in a nationwide sample of EDs. METHODS: We surveyed 69 US EDs, asking site investigators about the availability of health information technology in 2005-2006. Using multiple linear regression, we compared adoption of technology by ED type (emergency medicine residency affiliation, annual census, US region) to assess generalizability of the findings. RESULTS: Sixty-eight EDs (99%) provided information about health information technology; 75% were affiliated with an emergency medicine residency, and all were urban. Most respondents had applications that simply relay information from one place to another, including patient tracking (74%); ordering tests (laboratory 57%, others 62%); and displaying prior visit notes (79%), ECGs (92%), laboratory (97%), and radiology (99%) results. A minority had more advanced applications, which seek to modify human behavior, including medication ordering (38%), allergy warnings (19%), and medication cross-reaction warnings (13%), and a few used bar coding (20%). There were no significant differences in technology adoption by ED type. CONCLUSIONS: This and prior studies suggest that some applications-particularly those relevant to modifying clinician behavior-are not widespread in US EDs, while others are. The reasons for this are unknown, but might include expense and unintended consequences. The fact that the emergency medicine community has not rushed to adopt certain applications presents challenges and opportunities. PMID- 21031044 TI - The role of prophylactic anticonvulsants in moderate to severe head injury. AB - BACKGROUND: Post-traumatic seizures cause secondary brain injury, contributing to morbidity and mortality after traumatic brain injury. Seizure activity may be undetectable if the patient is paralysed and ventilated. AIMS: The effect of prophylactic anticonvulsant therapy on the prevention of seizures after moderate to severe traumatic brain injury was studied. METHODS: A structured systematic literature review was performed. RESULTS: There may be a place for prophylactic anticonvulsants in the prophylaxis of early post-traumatic seizures. CONCLUSION: Further randomised controlled trials are needed to firmly establish the benefits of prophylactic anticonvulsants. PMID- 21031045 TI - Traumatic bronchial rupture: an unusual cause of tension pneumothorax. AB - Bronchial rupture is a rare and serious complication of blunt chest trauma, which can be easily overlooked on initial evaluation in the emergency room (ER) as the focus of the attending physician is diverted to more obvious external injuries which may not be of much significance. We present one such patient referred to us as a case of unresolved right-sided pneumothorax 2 days after intercostal drainage (ICD) tube placement. PMID- 21031046 TI - Use of bivalirudin for heparin-induced thrombocytopaenia after thrombolysis in massive pulmonary embolism: a case report. AB - A 68-year-old man was referred to the emergency department 6 h after onset of sudden acute dyspnoea. Immediate ECG showed sinus tachycardia with the typical S1 Q3-T3 pattern and incomplete right bundle branch block. The echocardiogram showed the presence of mobile thrombus in the right atrium, a distended right ventricle with free wall hypokinesia and displacement of the interventricular septum towards the left ventricle. Lung spiral computed tomography (CT) showed bilateral pulmonary involvement and confirmed the picture of a thrombotic system in the right atrium and caval vein. Thrombolytic treatment with recombinant tissue plasminogen activator (rt-PA) and heparin (alteplase 10 mg bolus, then 90 mg over 2 h) was administered. Six hours after thrombolysis bleeding gums and significant reduction in platelet count (around 50,000) were observed. Heparin was discontinued and bivalirudin (0.1 mg/kg bolus and 1.75 mg/kg per h infusion) plus warfarin was initiated and continued for 5 days until the international normalised ratio (INR) was within the therapeutic range (2.0-3.0) for 2 consecutive days, with concomitant platelet count normalisation. Lung spiral and lower abdominal CT before discharge did not show the presence of clots in the pulmonary arteries of the right and left lung. This case suggests that bivalirudin could offer promise for use in patients with heparin-induced thrombocytopaenia (HIT) after thrombolysis for massive pulmonary embolism. PMID- 21031047 TI - Ludwig's angina. PMID- 21031048 TI - Meckel's diverticulum-induced ileocolonic intussusception. PMID- 21031049 TI - Echo-enhanced needles for short-axis ultrasound-guided vascular access. PMID- 21031050 TI - Integration of modern genetic knowledge and technology into public health in India. PMID- 21031051 TI - Genetics in public health: Rarely explored. AB - The availability and the integration of genetic information into our understanding of normal and abnormal growth and development are driving important changes in health care. These changes have fostered the hope that the availability of genetic information will promote a better understanding of disease etiology and permit early, even pre-symptomatic diagnosis and preventive intervention to avoid disease onset. Hence, our aim was to review and provide the insight into the role of genetics in public health and its scope as well as barriers. The use of genetics along with their goals and essential public health functions are discussed. From the era of eugenics to the present era, this area has seen many turns in which geneticists have put through their effort to tie together the strings of both molecular genetics and public health. Though still the dark clouds of eugenics, the predictive power of genes, genetic reductionism, non-modifiable risk factors, individuals or populations, resource allocation, commercial imperative, discrimination and understanding and education are hanging above. The technological and scientific advances that have fundamentally changed our perception of human diseases fuel the expectations for this proactive health. PMID- 21031052 TI - Haplotype diversity and linkage disequilibrium at the DRD2 locus among the tribes of western and southern regions of India. AB - BACKGROUND: Dopamine receptor D2 (DRD2) is an important gene having functional significance in the fields of neuropsychiatry and pharmacology and also has importance in evolutionary studies. MATERIALS AND METHODS: This study was undertaken to find out the haplotype distribution and linkage disequilibrium (LD) pattern for the three TaqI sites (TaqI 'A', TaqI 'B' and TaqI 'D') in the DRD2 gene in 232 unrelated individuals from five ethno-linguistically distinct endogamous tribal populations; Siddis and Gonds of Uttara Kannada district, Karnataka; Varli and Kolgha of Valsad district, Gujarat; and Dangi Konkana of Dang district, Gujarat. The genotype data obtained after molecular analysis of the three DRD2 sites was subjected to statistical analysis such as calculation of allele frequencies, haplotype frequencies among others. Subsequently, a neighbor joining tree was also constructed from the data obtained. RESULTS: The three DRD2 sites were found to be polymorphic in all the populations. All the populations showed high levels of heterozygosities. Out of the eight possible haplotypes, most populations shared seven haplotypes. Of all the populations, Siddis showed the highest frequency of the ancestral haplotype B2D2A1 (11.4%). Significant LD was found to exist for TaqI 'A' and TaqI 'B' sites in both the populations. CONCLUSION: The findings are in concurrence with those from other Indian studies, especially from Dravidian-speaking South Indian populations. Similar pattern of diversity observed for ethnically and linguistically diverse populations in the present study is indicative of complex structure of Indian populations. PMID- 21031053 TI - Opportunity for natural selection among some selected population groups of Northeast India. AB - BACKGROUND: Selection potential based on differential fertility and mortality has been computed for seven population groups inhabiting different geographical locations of Northeast India. MATERIALS AND METHODS: Crow's as well as Johnston and Kensinger's index have been used for the present purpose. RESULTS AND CONCLUSION: Irrespective of the methodology, the total index of selection was found to be highest among the Deoris followed by the Kaibartas. The lowest selection index was found among the Oraon population. If the relative contribution of fertility and mortality components to the total index is considered to be multiplicative, it is observed that in all these communities the fertility component exceeds that of mortality component, which may indicate initiation of demographic transitional phase in the selected populations with the betterment of healthcare and socioeconomic condition within the last few decades. PMID- 21031054 TI - Genetic variations of beta-MYH7 in hypertrophic cardiomyopathy and dilated cardiomyopathy. AB - CONTEXT: Hypertrophic cardiomyopathy (HCM) is known to be manifested by mutations in 12 sarcomeric genes and dilated cardiomyopathy (DCM) is known to manifest due to cytoskeletal mutations. Studies have revealed that sarcomeric mutations can also lead to DCM. Therefore, in the present study, we have made an attempt to compare and analyze the genetic variations of beta-myosin heavy chain gene (beta MYH7), which are interestingly found to be common in both HCM and DCM. The underlying pathophysiological mechanism leading to two different phenotypes has been discussed in this study. Till date, about 186 and 73 different mutations have been reported in HCM and DCM, respectively, with respect to this gene. AIM: The screening of beta-MYH7 gene in both HCM and DCM has revealed some common genetic variations. The aim of the present study is to understand the pathophysiological mechanism underlying the manifestation of two different phenotypes. MATERIALS AND METHODS: 100 controls, 95 HCM and 97 DCM samples were collected. Genomic DNA was extracted following rapid nonenzymatic method as described by Lahiri and Nurnberger (1991), and the extracted DNA was later subjected to polymerase chain reaction (PCR) based single stranded conformation polymorphism (SSCP) analysis to identify single nucleotide polymorphism (SNP)s/mutations associated with the diseased phenotypes. RESULTS AND CONCLUSION: Similar variations were observed in beta-MYH7 exons 7, 12, 19 and 20 in both HCM and DCM. This could be attributed to impaired energy compromise, or to dose effect of the mutant protein, or to even environmental factors/modifier gene effects wherein an HCM could progress to a DCM phenotype affecting both right and left ventricles, leading to heart failure. PMID- 21031055 TI - Association of polymorphisms in leptin receptor gene with obesity and type 2 diabetes in the local population of Coimbatore. AB - BACKGROUND: Candidate gene association studies are very relevant to the area of clinical pharmacology. As information on candidate genes and candidate single nucleotide polymorphisms increases, a number of such candidates can be studied in a population to explore their association with their susceptible disease. One such attractive and popular Single Nucleotide Polymorphism (SNP) candidate for obesity is the gene coding for leptin receptor. The leptin receptor gene (LEPR) polymorphism plays an important role in obesity and type 2 diabetes. But the role of this polymorphism is not yet studied in Indian population. Hence, the study focused to explore the association of leptin receptor polymorphisms (K109R, Q223R and K656N) with obesity and type 2 diabetes in both diabetic and non-diabetic subjects recruited from the local population of Coimbatore. MATERIALS AND METHODS: Genotypic analysis for the three polymorphisms has been made for 300 subjects (150 diabetic and 150 non-diabetic) with the age range of 40-60 years using conventional Polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) techniques in a case-control fashion. Allele frequencies were estimated based on the gene count method. Correlation was made with phenotypic variables including body mass index (BMI), waist-to-hip ratio (WHR), insulin and leptin levels for those polymorphisms. RESULTS AND CONCLUSION: Among the polymorphisms tested in this study, significant association with BMI (P < 0.05), WHR (P < 0.05) leptin (P < 0.001) and insulin (P < 0.0001) was observed for the SNP Q223R, whereas in the case of the other two polymorphisms the association was not statistically significant. The significance value was calculated based on the chi(2) test. The controls are also found to have a higher frequency of homozygous mutants for Q223R and are significantly associated with obesity. These findings support the hypothesis that Q223R polymorphism is associated with obesity. It can be speculated that the controls showing the same allele may develop Type 2 diabetes at a later stage and Q223R can act as a strong marker. PMID- 21031056 TI - Null association between ACE gene I/D polymorphism and diabetic nephropathy among multiethnic Malaysian subjects. AB - BACKGROUND: Wide inter-ethnic allelic variations of the Angiotensin Converting Enzyme (ACE) i nsertion-deletion (I/D) gene polymorphism were thought to be responsible for the conflicting gene-diabetic nephropathy disease association worldwide. We have investigated the genetic susceptibility of the ACE gene to diabetic nephropathy in the multiethnic Malaysian population. MATERIALS AND METHODS: A total of 137 healthy (control) and 256 diabetic subjects were recruited. The diabetic subjects were further subdivided according to their nephropathy status based on urinary albumin-creatinine ratio (ACR) and glomerular filtration rate (GFR). Triple primer polymerase chain reaction (PCR) was used for ACE I/D genotyping. Subsequently, populationwide genetic analysis and gene disease association studies were performed. RESULTS: The genotype frequencies in all subgroups were in Hardy-Weinberg equilibrium. Similar allelic and genotypic frequency of ACE I/D gene polymorphism was observed between healthy controls versus pooled type 2 diabetes mellitus (T2DM) subjects, and normoalbuminuria versus microalbuminuria, macroalbuminuria and End Stage Renal Failure (ESRF) (P > 0.05). Neither ethnicity nor gender exerted any influence on the ACE I/D gene polymorphism (P > 0.05), with the exception of the Chinese ethnic group which exhibited a higher frequency of ID genotype (P = 0.042). A multinomial logistic regression model showed that predictive factors including age, systolic blood pressure (SBP), high density lipoprotein (HDL) and glycosylated hemoglobin (HbA1C) were independently associated with diabetic nephropathy, in that order. CONCLUSION: The I/D polymorphism of the ACE gene is not significantly associated with both T2DM and/or diabetic nephropathy in this Malaysian population regardless of ethnicity and gender. PMID- 21031058 TI - Triploidy in a fetus following amniocentesis referred for maternal serum screening test at second trimester. AB - Amniocentesis was carried out at 17 weeks gestation in a 27-year-old woman, following an abnormal maternal serum screening (MSS) test. MSS test was carried out primarily to estimate the risk of trisomy for chromosome 21. The maternal serum markers used were alpha-fetoprotein (AFP), human chorionic gonadotrophin (hCG), and unconjugated estriol (uE3), together with maternal age. The fetus was identified as screen-positive for Edward's syndrome (trisomy 18), with low uE3, normal AFP and hCG levels. The calculated risk for trisomy 18 was more than 1:50. To identify any possible chromosomal abnormality, cytogenetic investigation was carried out on the amniotic fluid sample. The fetus's karyotype showed triploidy with 69, XXX chromosome complement in all the metaphase spreads obtained from three different cultures, using GTG banding technique. Upon termination of the fetus, gross abnormalities indicative of triploidy were present in the fetus. PMID- 21031057 TI - Investigation of chromosomal aberrations in Egyptian hepatocellular carcinoma patients by fluorescence in situ hybridization. AB - BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) is a very common and highly malignant tumor, associated mainly with chronic viral hepatitis, cirrhosis of any cause, aflatoxin exposure and ethanol consumption. Cytogenetic analysis on HCC has been limited because of poor hepatocyte growth in vitro. Conventional cytogenetic studies have demonstrated frequent abnormalities of specific chromosomes in HCC. Molecular cytogenetic approaches have been applied only rarely in the characterization of HCC. The main aim of this study was to evaluate genetic aberrations of different chromosomes in HCC. The study included 35 patients with HCC, who have been diagnosed and treated at National Cancer Institute, Cairo University, Egypt. The clinico-pathologic features of the studied patient were collected from patient's files. MATERIALS AND METHODS: Interphase cytogenetics by fluorescence in situ hybridization with the use of a panel of centromere-associated DNA probes for chromosomes 1, 4, 8, 9, 13, 17, 20 and Y were performed on paraffin-embedded HCC specimens. RESULTS: The most common chromosomal aberrations detected were gain of chromosomes 8 in 12 cases (34.28%), 17 in 6 cases (17.14%). Loss of chromosome Y was detected in 6 of male cases (30%). Monosomy 4 was also detected in 5 cases (14.28%). Negative correlation could be detected only between chromosome 4 and 8. (r = -0.381, P < 0.05). Correlations between gain or loss of chromosomes and the different clinicopathologic parameters in the patients investigated, indicated negative correlation between: chromosome Y and age and chromosome 1 and cirrhosis. CONCLUSION: Gains and losses of DNA found in this study probably involve oncogenes and tumor suppressor genes that play a role in the puzzle of hepatocarcinogenesis. PMID- 21031059 TI - Phenotypic correlations in a patient with ring chromosome 22. AB - Ring chromosome 22, a rare cytogenetic anomaly, has been described in over 60 cases in the medical literature. The aim of this report was to present a case carrying ring chromosome 22, and her family.It is a case report of a patient presented at Medical Faculty of Cukurova University in Turkey.An 8-year-old girl with ring chromosome 22 and her family were evaluated cytogenetically and clinically.A chromosome analysis of the proband revealed a de novo 46, XX, r(22)(p11.2;q13) karyotype. Our subject demonstrated the prominent features of this syndrome including profound mental retardation, language impairment, dysmorphic features, lack of speech, hyperactivity, and behavioral disorders.There is lack of consistency between the physical abnormalities that we observed in our subject and those observed for such patients in the literature. The wide range of manifestations observed in patients with this cytogenetic alteration is probably due to size differences in the deleted region. PMID- 21031060 TI - Sickle cell hemoglobinopathies in district Bhopal. PMID- 21031061 TI - Significance of t (8: 14) in CLL? PMID- 21031062 TI - Hair transplantation surgery - its current status. PMID- 21031063 TI - Review of factors affecting the growth and survival of follicular grafts. AB - Great strides have been made in hair restoration over the past 20 years. A better understanding of natural balding and non-balding patterns along with more respect for ageing has helped guide proper hairline design. Additionally, the use of smaller grafts has created a significantly improved natural appearance to the transplanted grafts. Inconsistent growth and survival of follicular grafts, however, has continued to be a problem that has perplexed hair restoration surgeons. This review attempts to explore the stresses affecting grafts during transplantation and some of the complexities involved in graft growth and survival. These authors reviewed the literature to determine the primary scope of aspects influencing growth and survival of follicular grafts. This scope includes patient selection, operating techniques, graft care, storage solutions and additives. The primary focus of the hair restoration surgeons should first be attention to the fundamentals of hair care, hydration, temperature, time out of body and gentle handling. Factors such as advanced storage solutions and additives can be helpful once the fundamentals have been addressed. PMID- 21031064 TI - Follicular unit extraction hair transplant. AB - Hair transplantation has come a long way from the days of Punch Hair Transplant by Dr. Orentreich in 1950s to Follicular Unit Hair Transplant (FUT) of 1990s and the very recent Follicular Unit Extraction (FUE) technique. With the advent of FUE, the dream of 'no visible scarring' in the donor area is now looking like a possibility. In FUE, the grafts are extracted as individual follicular units in a two-step or three-step technique whereas the method of implantation remains the same as in the traditional FUT. The addition of latest automated FUE technique seeks to overcome some of the limitations in this relatively new technique and it is now possible to achieve more than a thousand grafts in one day in trained hands. This article reviews the methodology, limitations and advantages of FUE hair transplant. PMID- 21031065 TI - Controversy: is there a role for adjuvants in the management of male pattern hair loss? AB - Patients with hair loss are seeking treatment at a younger age and during earlier stages. Not all need hair transplants. Because of the lack of assured management and the fear of side-effects, patients are turning to ineffective alternative remedies from self-claimed experts. In this report, we discuss the available treatment options and how best they can be used in combination to produce satisfactory results. The traditional approach consists of administration of drugs such as minoxidil and finasteride. We propose a hypothesis that nutritional supplements, 2% ketoconazole shampoo and low-level laser therapy along with finasteride 1 mg used once in 3 days with 2% minoxidil used everyday, given in a cyclical medicine program may be useful to manage hair loss and achieve new hair growth. The scientific rationale for such an approach is explained. The need for further studies to establish the efficacy of the regime is stressed upon. PMID- 21031066 TI - Hair Transplantation: Preventing Post-operative Oedema. AB - Swelling or oedema of forehead or eyelids is a common consequence of hair transplantation surgery. However, this results in increased morbidity and absence from work due to unaesthetic appearance. To study various physical and therapeutic modalities to reduce or completely prevent the occurrence of such oedema. Three hundred forty hair transplant patients were recruited in the study and were categorized into 8 groups depending upon the intervention employed. There were 32 dropouts in the study due to various reasons. Patients who were administered steroid with tumescent solution had the highest number of patients without oedema, with only 3 out of 117 patients developing oedema. Physical measures like position of head during sleeping, application of occlusion bands or ice packs did not show satisfactory results. Addition of triamcinolone to tumescent anaesthetic solution is a very effective technique of preventing post operative swelling. PMID- 21031067 TI - The use of botulinum toxin as primary or adjunctive treatment for post acne and traumatic scarring. AB - BACKGROUND: Botulinum toxin has been utilised successfully in many facial and extra facial regions to limit superfluous movement. Scars, whether traumatic or disease-related, are treated with many modalities. OBJECTIVE: To assess the available literature concerning the prophylactic use of botulinum toxin for the improvement in the cosmetic outcome of scars induced by surgery and to examine its role in the treatment of established scars alone, as also combined with other modalities. MATERIAL AND METHODS: The results of the prophylactic use of botulinum toxin to limit the resultant scarring from surgery are examined by a literature review. The primary and adjunctive use of botulinum toxin in the treatment of post acne and post surgical and traumatic scars is explored by case examples. RESULTS: Literature review and personal experience shows good Improvement in the appearance of scars with the use of botulinum toxin alone or with other adjuvant modalities in the treatment of scars. CONCLUSION: Botulinum toxin would appear to be useful both in the prophylaxis and treatment of certain types of scars. PMID- 21031068 TI - An Assessment of the Efficacy and Safety of CROSS Technique with 100% TCA in the Management of Ice Pick Acne Scars. AB - BACKGROUND: Chemical reconstruction of skin scars (CROSS) is a technique using high concentrations of trichloroacetic acid (TCA) focally on atrophic acne scars to induce inflammation followed by collagenisation. This can lead to reduction in the appearance of scars and cosmetic improvement. AIMS: The aim of this pilot study is to investigate the safety of the CROSS technique, using 100% TCA, for atrophic ice pick acne scars. SETTINGS AND DESIGN: Open prospective study. MATERIAL AND METHODS: Twelve patients with predominant atrophic ice pick post acne scars were treated with the CROSS technique, using 100% TCA, applied with a wooden toothpick, at two weekly intervals for four sittings. Efficacy was assessed on the basis of the physician's clinical assessment, photographic evaluation at each sitting and patient's feedback after the fourth treatment, and at the three-month and six-month follow-up period, after the last treatment. RESULTS: More than 70% improvement was seen in eight out of ten patients evaluated and good results (50 - 70% improvement) were observed in the remaining two patients. No significant side effects were noted. Transient hypopigmentation and hyperpigmentation was observed in one patient each. Physician's findings were in conformity with the patient's assessment. Three months after the last treatment, one patient noted a decrease in improvement with no further improvement even at the six-month follow-up period. CONCLUSION: The CROSS technique with 100% TCA is a safe, efficacious, cost-effective and minimally invasive technique for the management of ice pick acne scars that are otherwise generally difficult to treat. In few patients the improvement may not be sustained, probably due to inadequate or delayed collagenisation. PMID- 21031069 TI - Novel Technology in the Treatment of Acne Scars: The Matrix-tunable Radiofrequency Technology. AB - BACKGROUND: Despite the many advances, scarring, particularly acne or pimple scarring, does not have a satisfactory treatment. A new armamentarium in this field is this recently devised matrix-tunable radiofrequency technology, which utilizes radiofrequency emission in the treatment of acne scars. AIMS: To evaluate the efficiency of the new matrix-tunable radiofrequency technology in patients with acne scars of varying sizes. SETTINGS AND DESIGN: A prospective study of 30 randomly selected patients with acne scars was carried out. MATERIAL AND METHODS: Thirty healthy patients with different types of acne scars - ice pick, box and rolling type - were randomly selected. The scars were either shallow or deep, varied in size from 2 to 20 mm and ranged in number from 10 to 50. These patients were first treated with broad-spectrum antibiotics and local exfoliating agents (topical tretinoin 0.025%) and then subjected to matrix tunable radiofrequency technology. Each scar was treated at intervals of 1 month. A maximum of four such sittings were carried out. Patients were followed-up every 15 days. Results were noted at the end of 2 months and 6 months. Improvement was assessed by using the visual analog scale (VAS) at 2 months and 6 months, and results were noted in terms of percentage improvement of the whole face by calculating an average of percentage improvement on the basis of interviews of the patient and his/her accompanying relatives. The visual analog scaling was performed by means of high-resolution digital photographs taken at the baseline and at each subsequent visit. RESULTS: The VAS improvement in scars ranged from 10 to 50% at the end of 2 months to 20 to 70% at the end of 6 months. Of the 30 patients of acne scars, the cosmetic result was excellent (>60% improvement) in four, good (35-60% improvement) in 18 and moderate to poor (<35% improvement) in eight. A few patients reported burning sensation and a mild sunburn-like sensation for about 1 h after treatment. The patients reported a pinkish tone for 2-3 days. Importantly, with the help of some slight make up, all the 30 patients could return to work the following day. CONCLUSION: Matrix-tunable radiofrequency technology is a safe and economically viable option for the dermatologists for the treatment of acne scars, because of the effective results coupled with a low downtime. PMID- 21031070 TI - Finasteride and Male Breast Cancer: Does the MHRA Report Show a Link? AB - Finasteride is an important drug for the management of androgenetic alopecia. However, there are concerns about the possible side effects of the drug such as impotence. Recently stray reports have appeared about the occurrence of male breast carcinoma in patients who received the drug. These have been looked in to by Medicines and Health care products Regulatory Agency (MHRA). This article summarizes the MHRA report. PMID- 21031071 TI - Reconstruction of a large scalp defect by the sequential use of dermal substitute, self-filling osmotic tissue expander and rotational flap. AB - Large scalp defects pose a challenge for the surgeon. Here, we present a 31-year old male patient with a soft tissue defect on the temple with exposed bone. To allow reconstruction, we placed a self-filling osmotic expander in the subgaleal pocket for 12 weeks. The final volume of the tissue expander was 300 mL. In the last step, a rotational flap was created after removal of the tissue expander from its pocket. Thereby, a tension-free suturing was possible. The post-surgical healing was uncomplicated. Osmotic tissue expanders are a valuable tool for the closure of large tissue defects without the necessity of repeated filling procedures. PMID- 21031072 TI - Circumscribed congenital alopecias harbouring dual lesions. AB - Treatment of alopecia is often challenging for the clinician as it includes a spectrum of lesions ranging from congenital to acquired causes. We present three cases of congenital circumscribed alopecia, present since birth, clinically diagnosed as nevus sebaceous. Histopathological examination of the excised tissue showed syringocystadenoma papilliferum with dermatophytosis in one and nevus sebaceous with dermatophytosis in the other two cases. Although complete excision is the treatment of choice for these lesions, an antifungal agent is needed to eradicate the concurrent superficial mycosis. A careful histopathological examination of the lesional skin helps in identifying such unexpected dual lesions that would need further treatment. PMID- 21031073 TI - Basal cell carcinoma over chest wall (sternum) treated with dufourmentel flap: report of a case with review of literature. AB - Basal cell carcinoma (BCC) is the most common malignancy of the skin, accounting for approximately 70-80% of all cutaneous cancers. The commonest site of basal cell carcinoma is the face; 80% arise above a line from the corner of the mouth to the ear lobe. The lifetime ultraviolet radiation damage is the most important factor in its pathogenesis, and the vast majority is observed on sun-exposed skin. BCCs can develop in sun-protected areas, but its occurrence is rare. Here we are reporting a case of rare site of BCC with review of literature in a 65 year-old male who presented with a lesion over anterior chest wall. A clinical diagnosis of BCC was made and patient was subjected to excision biopsy. Biopsy revealed it to be a BCC and it was treated with a Dufourmentel flap. PMID- 21031074 TI - Giant lipoma of posterior neck with bleeding decubitus ulcer: a rare entity. AB - Giant lipomas are benign soft tissue tumours. They are found relatively rarely on the posterior part of the neck. Bleeding pressure ulcer in this giant tumour is a rare presentation. Surgical interventions in these tumours are very challenging because, sometimes, extension to the spinal cord and malignant change may occur, especially in old age. Knowledge of the anatomy and meticulous surgical techniques are needed for such giant lipomas. PMID- 21031075 TI - A case of papillary growth from the areola. PMID- 21031076 TI - Acne scar subcision. AB - Subcision is a simple and safe office surgery procedure for treatment of depressed acne scars. It can easily be combined with other treatments such as laser, dermaroller and scar revisions for maximum efficacy. PMID- 21031077 TI - Q-Switched Nd: YAG in the Treatment of Xanthelasma Palpebrarum. PMID- 21031078 TI - Silicone gel for hypertrophic scars. PMID- 21031079 TI - Disturbed Wnt Signalling due to a Mutation in CCDC88C Causes an Autosomal Recessive Non-Syndromic Hydrocephalus with Medial Diverticulum. AB - The etiology of non-syndromic hydrocephalus is poorly understood. Via positional cloning in a consanguineous family with autosomal recessive hydrocephalus we have now identified a homozygous splice site mutation in the CCDC88C gene as a novel cause of a complex hydrocephalic brain malformation. The only living patient showed normal psychomotor development at the age of 3 years and 3 months and her deceased aunt, who was assumed to suffer from the same condition, had mild mental retardation. The mutation in the affected patients, a homozygous substitution in the donor splice site of intron 29, resulted in a shorter transcript due to exclusion of exon 29 and loss of functional protein, as shown by Western blotting (p.S1591HfsX7). In normal human tissue panels, we found CCDC88C ubiquitously expressed, but most prominently in the fetal brain, especially in pons and cerebellum, while expression in the adult brain appeared to be restricted to cortex and medulla oblongata. CCDC88C encodes DAPLE (HkRP2), a Hook-related protein with a binding domain for the central Wnt signalling pathway protein Dishevelled. Targeted quantitative RT-PCR and expression profiling of 84 genes from the Wnt signalling pathway in peripheral blood from the index patient and her healthy mother revealed increased mRNA levels of CCDC88C indicating transcriptional upregulation. Due to loss of CCDC88C function beta-catenin (CTNNB1) and the downstream target LEF1 showed increased mRNA levels in the patient, but many genes from the Wnt pathway and transcriptional target genes showed reduced expression, which might be explained by a complex negative feedback loop. We have thus identified a further essential component of the Wnt signalling pathway in human brain development. PMID- 21031080 TI - Distinctive Phenotypic Abnormalities Associated with Submicroscopic 21q22 Deletion Including DYRK1A. AB - Partial monosomy 21 has been reported, but the phenotypes described are variable with location and size of the deletion. We present 2 patients with a partially overlapping microdeletion of 21q22 and a striking phenotypic resemblance. They both presented with severe psychomotor delay, behavioral problems, no speech, microcephaly, feeding problems with frequent regurgitation, idiopathic thrombocytopenia, obesity, deep set eyes, down turned corners of the mouth, dysplastic ears, and small chin. Brain MRI showed cerebral atrophy mostly evident in frontal and temporal lobes, widened ventricles and thin corpus callosum in both cases, and in one patient evidence of a migration disorder. The first patient also presented with epilepsy and a ventricular septum defect. The second patient had a unilateral Peters anomaly. Microarray analysis showed a partially overlapping microdeletion spanning about 2.5 Mb in the 21q22.1-q22.2 region including the DYRK1A gene and excluding RUNX1. These patients present with a recognizable phenotype specific for this 21q22.1-q22.2 locus. We searched the literature for patients with overlapping deletions including the DYRK1A gene, in order to define other genes responsible for this presentation. PMID- 21031081 TI - Expansion of the Spectrum of FLNA Mutations Associated with Melnick-Needles Syndrome. AB - Melnick-Needles syndrome (MNS) is a rare X-linked bone dysplasia characterised by facial dysmorphology and radiographic abnormalities [Melnick and Needles, 1966;97:39-48]. Previously, all published cases of MNS were associated with only 4 mutations [Robertson et al., 2003;33:487-491; Santos et al., 2010;152A:726 731], all localised within exon 22 of FLNA, the gene encoding the cytoskeletal protein filamin A. Here we report 3 new mutations in FLNA that are associated with MNS. One affected member of the first family with the mutation p.Y1229S presented with a stroke while this patient's daughter, previously known to be affected from a young age, developed multiple sclerosis. A second unrelated patient with a typical phenotype is shown to have the mutation c.1054G>T (p.G352W) within exon 7 of FLNA. A third individual with an atypical presentation but radiological findings very similar to those seen in classic MNS has a deletion likely to affect residues within repeat domain 14. These findings indicate that the mutational spectrum for MNS is wider than previously appreciated and has implications for genetic testing strategies employed to confirm a diagnosis of this rare disorder. PMID- 21031082 TI - A Novel LMNA Mutation Causes Altered Nuclear Morphology and Symptoms of Familial Partial Lipodystrophy (Dunnigan Variety) with Progeroid Features. AB - Dunnigan-type partial lipodystrophy (familial partial lipodystrophy, Dunnigan variety, FPLD2) can be caused by LMNA mutations. We identified a novel heterozygous LMNA mutation, P485R, in a patient referred to the International Registry of Werner Syndrome because of features consistent with that of progeroid disorder but who was wild type at the WRN locus. The novel mutation is located 2 amino acids away from the canonical FPLD mutations in exon 8 of the LMNA gene. Immunocytochemical analysis revealed abnormal nuclear morphology characteristic of laminopathies within primary fibroblast cultures, but not in a lymphoblastoid cell line, in keeping with previous observations. Our findings indicate that FPLD2 should be considered in the differential diagnosis of the Werner syndrome. PMID- 21031083 TI - An Illustrative Case of Neurofibromatosis Type 1 and NF1 Microdeletion. AB - We report on a patient with NF1 microdeletion and clinical manifestations that fulfill the diagnostic criteria for neurofibromatosis type 1 but also presenting features reminiscent of Proteus syndrome. PMID- 21031084 TI - Active surveillance for favorable-risk prostate cancer: a short review. AB - Active surveillance is becoming a more widely accepted management strategy in men with low-risk localized prostate cancer. This is in recognition of the knowledge that most men with such cancer are likely to die from other causes. The obvious benefits of active surveillance are reduced morbidity by delaying or avoiding radical gland therapy. These advantages should be balanced against appropriate selection criteria and triggers for moving to radical therapy while on active surveillance. The optimal method by which to identify the small number of men who will progress by use of clinical, biopsy, and imaging data is yet to be defined. Nevertheless, active surveillance is an appealing management option in selected men with prostate cancer and represents a solution to the significant problem of the overdiagnosis of clinically insignificant disease that accompanies prostate specific antigen (PSA) screening. PMID- 21031085 TI - Single positive core prostate cancer in a 12-core transrectal biopsy scheme: clinicopathological implications compared with multifocal counterpart. AB - PURPOSE: The incidence of single positive core prostate cancer at the time of biopsy appears to be increasing in the prostate-specific antigen (PSA) era. To determine the clinical implication of this disease, we analyzed surgical and pathological characteristics in comparison with multiple positive core disease. MATERIALS AND METHODS: Among 108 consecutive patients who underwent robotic radical prostatectomy following a diagnosis of prostate cancer based on a 12-core transrectal biopsy performed by the same method in a single institute, outcomes from 26 patients (Group 1) diagnosed on the basis of a single positive biopsy core and from 82 patients (Group 2) with multiple positive biopsy cores were analyzed. RESULTS: The preoperative PSA value, Gleason score, prostate volume, and D'Amico's risk classification of each group were similar. The proportion of intermediate+highrisk patients was 69.2% in Group 1 and 77.9% in Group 2 (p=0.22). Total operative time and blood loss were similar. Based on prostatectomy specimens, only 3 patients (11.5%) in Group 1 met the criteria for an indolent tumor (7.31% in Group 2). Although similarities were observed during preoperative clinical staging (p=0.13), the final pathologic stage was significantly higher in Group 2 (p=0.001). The positive-margin rate was also higher in Group 2 (11.5% vs. 31.7%, p=0.043). Despite similarity in upstaging after prostatectomy in each group (p=0.86), upgrading occurred more frequently in Group 1 (p=0.014, 42.5% vs. 19.5%). No clinical parameters were valuable in predicting upgrading. CONCLUSIONS: Most single positive core prostate cancer diagnoses in 12-core biopsy were clinically significant with similar risk stratification to multiple positive core prostate cancers. Although the positive margin rate was lower than in multiple positive core disease, an increase in Gleason score after radical prostatectomy occurred more frequently. PMID- 21031086 TI - Predictive factors of Gleason score upgrading in localized and locally advanced prostate cancer diagnosed by prostate biopsy. AB - PURPOSE: The Gleason score (GS) is an important factor that is considered when making decisions about prostate cancer and its prognosis. However, upgrading of the GS can occur between transrectal ultrasonography (TRUS) biopsy and radical prostatectomy. This study analyzed the clinical factors predictive of upgrading of the GS after radical prostatectomy compared with that at the time of TRUS biopsy. MATERIALS AND METHODS: We analyzed the medical records of 107 patients who had undergone radical prostatectomy. Patients were divided into two groups. Group 1 consisted of patients in whom the GS was not upgraded, and group 2 consisted of patients in whom the GS was upgraded. Associations between preoperative clinical factors and upgrading of the GS were analyzed. Preoperative clinical factors included age, prostate-specific antigen (PSA), prostate volume, PSA density, GS of TRUS biopsy, maximum core percentage of cancer, percentage of positive cores, number of biopsies, location of positive core with maximum GS, high-grade prostatic intraepithelial neplasia (HGPIN), inflammation on biopsy, and clinical stage. RESULTS: Among 85 patients, 42 (49%) patients had an upgraded GS after operation. TRUS biopsy core number of 12 or fewer (p=0.029) and prostate volume of 36.5 ml or less (p<0.001) were associated with upgrading of the GS. Preoperative clinical factors associated with nonupgrading of the GS were the detection of positive cores with a maximum GS at the apex (p=0.002) or in a hypoechoic lesion (p=0.002) in TRUS. CONCLUSIONS: If the positive cores with maximum GS are located at the apex or in a hypoechoic lesion in TRUS, we can expect that the GS will not be upgraded. In patients with the clinical predictive factors of a prostate volume of 36.5 ml or less and TRUS biopsy core number of less than 12, we can expect upgrading of the GS after radical prostatectomy, and more aggressive treatment may be needed. PMID- 21031088 TI - The learning curve for holmium laser enucleation of the prostate: a single-center experience. AB - PURPOSE: Holmium laser enucleation of the prostate (HoLEP) is known to have a steep learning curve and, as a result, its clinical usage has limitations. The purpose of this study was to analyze the learning curve and early complications following the HoLEP procedure. MATERIALS AND METHODS: A retrospective analysis was performed on 161 patients who had undergone the HoLEP procedure for lower urinary tract symptoms suggestive of benign prostatic hyperplasia (BPH) from July 2008 to September 2009. The procedure was done by two surgeons. Perioperatively, enucleated tissue weight, enucleation time, morcellation time, enucleation ratio (enucleation weight/transitional zone volume), and enucleation efficiency (enucleated weight/enucleation time) were analyzed, and early complications were assessed. RESULTS: Mean enucleation time, morcellation time, and enucleation ratio were 61.3 min (range, 10-180 min), 12.3 min (range, 2-60 min), and 0.66 (range, 0.07-2.51), respectively. In terms of efficiency, enucleation efficiency was 0.32 g/min (range, 0.02-1.25 g/min) and morcellation efficiency was 1.73 g/min (range, 0.1-7.7 g/min). Concerning the learning curve, enucleation efficiency was stationary after 30 cases (p<0.001), morcellation efficiency reached a learning curve at 20 cases (p=0.032), and enucleation ratio had no learning curve in this study. There were several cases of surgery-related complications, including bladder mucosal injury by the morcellator (13%), capsular injury during enucleation (7%), and conversion to a conventional resectoscopy procedure (15%), which showed a reduction in incidence with time. CONCLUSIONS: The learning curve of HoLEP is steep; however, it can be overcome gradually. Further study is necessary with respect to long-term postoperative follow-up. PMID- 21031087 TI - Surgical clip-related complications after radical prostatectomy. AB - PURPOSE: The aim of this study was to describe the surgical clip-related complications that can occur after open retropubic prostatectomy (RRP), pure laparoscopic prostatectomy (LRP), and robot-assisted laparoscopic radical prostatectomy (RALP). MATERIALS AND METHODS: A database of 641 patients who underwent RRP (n=439), LRP (n=49), and RALP (n=153) at our institution between January 2006 and April 2009 was reviewed to identify patients with complications related to the use of surgical clips. The median follow-up time for the entire cohort was 19.0 months (range, 1-42 months). RESULTS: Of the 641 patients, 25 (5.7%), 1 (2.0%), and 2 (1.3%) had a bladder neck contracture after RRP, LRP, and RALP, respectively. Two RRP patients had a bladder stone. In total, 6 patients had surgical clip-related complications. Metal clip migration was associated with 2 (8%) of the 25 RRP cases of bladder neck contracture and both (100%) of the RRP cases of bladder stone. Moreover, both (100%) of the RALP cases of bladder neck contractures were associated with Hem-o-lok clip migration into the anastomotic site. CONCLUSIONS: Surgical clips are prone to migration and may cause, or significantly contribute to, bladder neck contracture or the formation of bladder stones after radical prostatectomy. These findings also suggest that because the incidence of bladder neck contracture after RALP is low, the migration of Hem-o lok clips should be suspected when voiding difficulty occurs after RALP. PMID- 21031090 TI - Analysis of the factors causing bladder irritation after transurethral resection of the prostate. AB - PURPOSE: Approximately 20% to 30% of patients with benign prostatic hyperplasia (BPH) require medication or supplementary treatment for their continuous irritative bladder symptoms after transurethral resection of the prostate (TURP). The purpose of this study was to identify any factors related to continuous bladder irritation in patients after TURP. MATERIALS AND METHODS: Of all patients who underwent TURP from January 2000 to December 2007, 160 who underwent long term follow-up were selected for this study. The International Prostate Symptom Score (IPSS) was assessed 12 months after TURP, and the patients were divided into two groups: one group with an irritative bladder symptom score on the IPSS of 7 or less (non-irritative group) and another group with an irritative bladder symptom score on the IPSS of 8 or greater (irritative group). Preoperative urodynamic study variables, preoperative and postoperative IPSS, and the shape of the prostate upon transrectal ultrasonography (TRUS) were analyzed. RESULTS: Of the 160 patients, 93 patients were assigned to the non-irritative group, and 67 were assigned to the irritative group. Initial irritative bladder symptoms were significantly different between the two groups (p<0.05). Also, a retrourethral enlarged prostate was more frequently observed upon TRUS in the irritative group. Symptoms of urinary frequency, incontinence, and urgency were significantly greater in the irritative group. Although there was no significant difference in the preoperative quality of life between the two groups, postoperative quality of life was significantly worse in the irritative group. CONCLUSIONS: The shape of the prostate and the preoperative irritation score correlated significantly with the postoperative severity of irritative bladder symptoms. Therefore, physicians should be cautious when performing TURP in patients with a retrourethral enlarged prostate and severe irritative symptoms. PMID- 21031089 TI - Clinical and urodynamic significance of morphological differences in intravesical prostatic protrusion. AB - PURPOSE: The objectives of this study were to evaluate whether morphologic differences correlated with urodynamic and clinical characteristics in patients with benign prostatic hyperplasia (BPH) with intravesical prostatic protrusion (IPP) of trilobar or bilobar adenoma. MATERIALS AND METHODS: Between January 2008 and June 2009, 72 male patients who had undergone transurethral resection (TUR) owing to BPH with IPP were included in this study. They underwent preoperative urodynamic studies, the International Prostate Symptom Score (IPSS)/quality of life (QoL), maximal flow rate (Qmax), post-voiding residual urine volume (PVR), transrectal ultrasonography (TRUS), and serum prostate-specific antigen (PSA) measurement. The patients were classified into 2 groups (the trilobar and bilobar adenoma groups) on the basis of video findings during the TUR operation. RESULTS: The trilobar and bilobar adenoma groups consisted of 37 patients and 35 patients, respectively. The Mean+/-SD IPP, prostate volume (PV), and transition zone volume of the trilobar and bilobar adenoma groups were 11.8+/-5.2 mm and 9.0+/-3.8 mm (p=0.014), 81.1+/-25.8 g and 59.3+/-22.5 g (p<0.001), and 49.6+/-20.6 g and 34.8+/-19.4 g (p=0.003), respectively. The Mean+/-SD PSA, bladder contractility index (BCI), and bladder outlet obstruction index (BOOI) were 4.6+/-2.5 ng/ml and 3.5+/-1.7 ng/ml (p=0.042), 119.8+/-33.4 and 87.7+/-24.4 (p<0.001), and 62.6+/ 29.5 and 44.6+/-20.4 (p=0.005), respectively. There were no significant differences in IPSS/QoL, Qmax, PVR, acute urinary retention, or detrusor overactivity in the 2 groups. CONCLUSIONS: IPP has two morphologic types of trilobar or bilobar enlargement. The PV, BOOI, and BCI were significantly smaller in the bilobar adenoma group than in the trilobar adenoma group. PMID- 21031091 TI - The different reduction rate of prostate-specific antigen in dutasteride and finasteride. AB - PURPOSE: To compare and analyze the therapeutic effects and changes in the prostate-specific antigen (PSA) level with treatment with finasteride or dutasteride for benign prostatic hyperplasia (BPH) for 1 year. MATERIALS AND METHODS: We retrospectively investigated patients who suffered from BPH for 1 year between January 2005 and December 2008. For treatment groups, we divided the patients into two groups: one was treated with alfuzosin and finasteride and the other was treated with alfuzosin and dutasteride. At the beginning of treatment, the patients underwent transrectal ultrasonography and measurement of urine flow rate, residual urine volume, PSA, and International Prostate Symptom Score (IPSS). Patients with diseases affecting urinary function were excluded. We not only analyzed the data at the time of initial treatment, but also after 1 year of treatment. A total of 219 patients were able to be evaluated for 1 year. RESULTS: Both finasteride and dutasteride reduced PSA and prostate volume significantly. The comparison between groups showed a more significant reduction of PSA (p=0.020) and prostate volume (p=0.052) in the dutasteride group. Other parameters did not differ significantly between the groups. CONCLUSIONS: 5-alpha Reductase inhibitors for BPH treatment reduced PSA and prostate volume significantly when the patients were treated for 1 year. Administration of dutasteride is considered to be more effective in reducing PSA and prostate volume. Therefore, dutasteride should not be considered equivalent to finasteride in the reduction rate of PSA. The intensity of dutasteride must be reevaluated in comparison with finasteride. PMID- 21031093 TI - Evaluation of possible predictive variables for the outcome of shock wave lithotripsy of renal stones. AB - PURPOSE: The aim of this study was to evaluate possible predictive variables for the outcome of shock wave lithotripsy (SWL) of renal stones in a single center. MATERIALS AND METHODS: Between March 2008 and March 2010, a retrospective review was performed of 115 patients who underwent SWL for solitary renal stones. The patients' characteristics and stone size, location, skin-to-stone distance (SSD), and Hounsfield units (HU) of stone were reviewed. The impact of the possible predictors on the disintegration of the stones was evaluated by logistic regression analysis. Receiver operator characteristic (ROC) curves were generated to compare the predictive powers of the variables. RESULTS: Seventy-nine patients (68.7%) had successful outcomes, whereas 36 patients (31.3%) had residual stones. Significant differences were found in the mean size and mean HU of the stones (size: 8.34+/-3.58 mm vs. 13.57+/-5.41 mm, p<0.001; HU: 675.29+/-254.34 vs. 1,075.00+/-290.41, p<0.001). In the unadjusted model, age, stone size, and stone density were significant predictors. In the reduced model, stone density and size were significant predictors for the outcome of SWL. The area under the ROC curve (AUC) was significantly higher for stone density and size than for the other parameters, but the AUC between stone density and size did not differ significantly (stone density: 0.874, stone size: 0.827, p=0.388). CONCLUSIONS: Stone density and size were significant predictors of the outcome of SWL for renal stones less than 2.0 cm in diameter. We should consider HU and stone size when making decisions on the treatment of renal stones. PMID- 21031092 TI - Suprapubic cystostomy: risk analysis of possible bowel interposition through the percutaneous tract by computed tomography. AB - PURPOSE: The most serious complication of suprapubic cystostomy is bowel injury. By computed tomography (CT), we investigated the risk factors of possible bowel interposition through the percutaneous suprapubic cystostomy tract. MATERIALS AND METHODS: From September to October 2009, we consecutively reviewed 795 abdominopelvic CT scans of adult patients performed for various reasons in our hospital. From these scans, we selected the films wherein the urinary bladder was distended more than 6 cm above the symphysis pubis. We then determined whether the bowel was interposed between the bladder and the skin at the routine puncture site of suprapubic cystostomy (the midline of the abdomen 3 cm above the upper margin of the symphysis pubis). We analyzed which factors influenced the possibility of the bowel being interposed between the bladder and the skin at the suprapubic puncture site. RESULTS: A total of 226 CT (148 males, 78 females) scans were selected. The mean patient age was 63 years (range, 26-84 years). The mean distance between the upper margin of the symphysis pubis and the umbilicus was 14.4 cm (range, 7.2-21.0 cm). In the multivariate analysis, obesity, a positive history of radical pelvic surgery, and a short distance (<=11 cm) between the symphysis pubis and the umbilicus had significant correlations with bowel interposition in the assumed tract. CONCLUSIONS: When performing a suprapubic cystostomy, extreme caution is needed to avoid possible bowel injury in patients who are obese, had a previous radical pelvic operation, or have a short distance between the upper margin of the symphysis pubis and the umbilicus. PMID- 21031094 TI - Use of NTrap(r) during Ureteroscopic Lithotripsy for Upper Ureteral Stones. AB - PURPOSE: This study aimed to determine the value of the NTrap(r) (Cook Urological INC, USA), which was designed to block the upward movement of stones during ureteroscopic lithotripsy. MATERIALS AND METHODS: We reviewed the data of 144 patients who underwent ureteroscopic lithotripsy for an upper ureteral stone from June 2006 to May 2010. Sixty-eight patients who underwent ureteroscopic lithotripsy without the use of the NTrap(r) were assigned to Group I and 76 patients who underwent ureteroscopic lithotripsy with the NTrap(r) were assigned to Group II. The size of the stones, operation time, success rate, and pre- and postoperative complications were compared retrospectively between the two groups. RESULTS: THE MEAN AGE OF THE PATIENTS (GROUP I: 35.8 years; Group II: 32.6 years) and the sex ratios were not significantly different between the two groups. The mean size of the stones was 6.9 mm and 7.4 mm, which also was not significantly different between the two groups. The mean operation time was 82.7 minutes and 78.7 minutes. The operation time was shorter in Group II, but the difference was not significant. The success rate of stone removal was 89.7% and 98.7% in Groups I and II, respectively; Group II showed a significantly higher success rate. Two cases of ureteral perforation and one case of ureteral avulsion occurred in Group I, and one case of ureteral perforation occurred in Group II. CONCLUSIONS: NTrap(r), which is an instrument used to assist during ureteroscopic lithotripsy, can be considered to be an effective tool that blocks the upward movement of the stone and aids in safe stone removal. PMID- 21031095 TI - Sarcomatoid carcinoma of the urinary bladder: a clinicopathological study of 4 cases and a review of the literature. AB - Sarcomatoid carcinoma (SC) of urinary bladder is a rare tumor exhibiting aggressive behavior. Here we are reviewing the pathologic and clinical characteristics of 4 consecutive cases of this rare tumor. Three out of 4 patients were males and one female. The median age was 72.8 years (range, 60-79 years). Patients underwent transurethral resection of bladder tumor and the diagnosis of bladder SC was established on the pathologic examination of the resected bladder tissue. Despite treatment all patients died within 22 months of the diagnosis of SC. SC of the bladder are true biphasic malignant neoplasm exhibiting morphologic and immunohistochemical evidence of epithelial and mesenchymal differentiation with the presence or absence of heterologous elements. The aggressive of the tumor precludes radical therapy whenever possible, since adjuvant therapy seems to have little effect. PMID- 21031097 TI - Erratum: the effect of the partial obstruction site of the renal vein on testis and kidney in rats: is the traditional animal model suitable for varicocele research? AB - [This corrects the article on p. 565 in vol. 51, PMID: 20733964.]. PMID- 21031096 TI - Two different renal cell carcinomas and multiple angiomyolipomas in a patient with tuberous sclerosis. AB - We report a case of tuberous sclerosis associated with two histologically different renal cell carcinomas (RCCs) and multiple angiomyolipomas (AMLs) in the same kidney. A 43-year-old female was admitted to our hospital with left flank pain and a huge palpable mass in the left flank area. Abdominal computed tomography revealed two concurrent RCCs and multiple AMLs in the left kidney. Because of the clinical suspicion of RCC, the patient underwent left radical nephrectomy. On gross examination, the total size of the resected left kidney was 30.5*17*8 cm. Microscopically, the upper pole tumor features were consistent with chromophobe RCC and the midpole tumor was a clear-cell RCC. The multifocal masses in the remaining remnant parenchyma were AMLs. Six months after surgery, the patient is healthy without signs of tumor recurrence. PMID- 21031098 TI - Protecting our fledgling families: a case for relationship-focused family life education programs. PMID- 21031099 TI - Keeping an eye on future: medical tourism. PMID- 21031100 TI - Knowledge, truth, and social reality: an introductory note on qualitative research. PMID- 21031101 TI - E-waste management: as a challenge to public health in India. PMID- 21031102 TI - Clinical manifestations and trend of dengue cases admitted in a tertiary care hospital, udupi district, karnataka. AB - BACKGROUND: India is one of the seven identified countries in the South-East Asia region regularly reporting dengue fever (DF)/dengue hemorrhagic fever (DHF) outbreaks and may soon transform into a major niche for dengue infection in the future with more and more new areas being struck by dengue epidemics OBJECTIVE: To study the clinical manifestations, trend and outcome of all confirmed dengue cases admitted in a tertiary care hospital. STUDY DESIGN: Record-based study conducted in a coastal district of Karnataka. Required data from all the laboratory confirmed cases from 2002 to 2008 were collected from Medical Records Department (MRD) and analyzed using SPSS 13.5 version. RESULTS: Study included 466 patients. Majority were males, 301(64.6%) and in the and in the age group of 15-44 years, 267 (57.5%). Maximum number of cases were seen in 2007, 219 (47%) and in the month of September, 89 (19.1%). The most common presentation was fever 462 (99.1%), followed by myalgia 301 (64.6%), vomiting 222 (47.6%), headache 222 (47.6%) and abdominal pain 175 (37.6%). The most common hemorrhagic manifestation was petechiae 84 (67.2%). 391 (83.9%) cases presented with dengue fever, 41 (8.8%) dengue hemorrhagic fever, and 34 (7.3%) with dengue shock syndrome. Out of 66 (14.1%) patients who developed clinical complications, 22 (33.3%) had ARDS and 20 (30.3%) had pleural effusion. Deaths reported were 11(2.4%). CONCLUSION: Community awareness, early diagnosis and management and vector control measures need to be strengthened, during peri-monsoon period, in order to curb the increasing number of dengue cases. PMID- 21031103 TI - Age heaping and accuracy of age data collected during a community survey in the yavatmal district, maharashtra. AB - BACKGROUND: Age is an important variable in epidemiological studies and an invariable part of community-based study reports. AIMS: The aim was to assess the accuracy of age data collected during community surveys. SETTINGS AND DESIGN: A cross-sectional study was designed in rural areas of the Yavatmal district. MATERIALS AND METHODS: Age data were collected by a house-to-house survey in six villages. An open-ended questionnaire was used for data collection. STATISTICAL ANALYSIS: Age heaping and digit preference were measured by calculating Whipple's index and Myers' blended index. Age Ratio Scores (ARS) and Age Accuracy Index (AAI) were also calculated. RESULTS: Whipple's index for the 10-year age range, i.e., those reporting age with terminal digit "0" was 386.71. Whipple's index for the 5-year range, i.e., those reporting age with terminal digit '0' or '5' was 382.74. Myer's blended index calculated for the study population was 41.99. AAI for the population studied was 14.71 with large differences between frequencies of males and females at certain ages. CONCLUSION: The age data collected in the survey were of very poor quality. There was age heaping at ages with terminal digits '0' and '5', indicating a preference in reporting such ages and 42% of the population reported ages with an incorrect final digit. Innovative methods in data collection along with measuring and minimizing errors using statistical techniques should be used to ensure the accuracy of age data which can be checked using various indices. PMID- 21031104 TI - Diabetes prevalence and its risk factors in rural area of Tamil Nadu. AB - OBJECTIVE: To estimate the usefulness of the Indian diabetes risk score for detecting undiagnosed diabetes in the rural area of Tamil Nadu. MATERIALS AND METHODS: The present study was conducted in the field practice area of rural health centers (Chunampett and Annechikuppam, Tamil Nadu), covering a population of 35000 from February to March 2008 by using a predesigned and pretested protocol to find out the prevalence and the risk of diabetes mellitus in general population by using Indian diabetes risk score. RESULTS: 1936 respondents comprising 1167 (60.27%) females and 769 (39.73%) males were studied. Majority 1203 (62.50%) were Hindus. 1220 (63.%) had studied up to higher secondary. 1200 (62%) belonged to lower and lower-middle socio-economic class. A large number of the subjects 948 (50%) were below 35 years of age. Most of the respondents 1411 (73%) indulged in mild to moderate physical activity. 1715 (87.91%) had no family history of diabetes mellitus. 750 (39.64%) individuals were in the overweight category (>25 BMI). Out of these overweight persons, 64% had high diabetic risk score. It is observed that chances of high diabetic score increase with the increase in BMI. Prevalence of diabetes in studied population was 5.99%; out of these, 56% known cases of diabetes mellitus had high (>60) IDRS. Co-relation between BMI and IDRS shows that, if BMI increases from less than 18.50 to more than 30, chances of high risk for developing diabetes mellitus also significantly increase. CONCLUSIONS: This study estimates the usefulness of simplified Indian diabetes risk score for identifying undiagnosed high risk diabetic subjects in India. This simplified diabetes risk score has categorized the risk factors based on their severity. Use of the IDRS can make mass screening for undiagnosed diabetes in India more cost effective. PMID- 21031106 TI - Domestic violence against women and their mental health status in a colony in delhi. AB - BACKGROUND: Violence against women is a major public health and human rights issue in the world today. This study was conducted to assess the consequences of domestic violence on the mental health of women of reproductive age group. MATERIALS AND METHODS: A community-based, cross-sectional study was conducted in Raj Nagar- I, urban locality in west Delhi near Palam. 350 women of 15-49 years age group residing in the community were selected by stratified random sampling. These women were administered an interview schedule adapted from WHO multi country study on women's health and domestic violence. They were assessed for the presence of domestic violence. Mental health status of these women was estimated by using self-reporting questionnaire 20. Data were analyzed using SPSS 12 software. The test applied was chi square test for proportion and binary logistic regression. RESULTS: 42.8% of the women reported one or the other types of violence. 34.9% of the women reported either physical or sexual violence ever in life. 29.1% of the women reported either physical or sexual violence in past 1 year (current violence). 12% of the women reported mental ill health. Women who had experienced domestic violence were more likely to report mental ill health status and suicidal tendencies as compared to women who had not experienced violence. CONCLUSIONS: Domestic violence is associated with mental ill health. PMID- 21031105 TI - Nutrient intake amongst rural adolescent girls of wardha. AB - OBJECTIVE: To assess the nutrient intake of rural adolescent girls. MATERIALS AND METHODS: The cross-sectional study was carried in four adopted villages of the Department of Community Medicine, M.G.I.M.S., Sewagram. A household survey was carried out in the villages. A list of all the adolescent girls in the age group of 10-19 years was prepared by enumeration through house-to-house visit. All adolescent girls were included in the study. A pre-designed and pre-tested questionnaire was used to collect data on socio-demographic variables and anthropometric variables. A 24 h recall method was used to assess nutrient intake. Data generated was entered and analyzed using epi_info 2000. Nutrient intake was compared with ICMR Recommended Dietary Allowances. Nutritional status was assessed by BMI for age. RESULTS: The mean height of the adolescent girls was 142.9 cm. Overall, 57% of the adolescents were thin (BMI for age <5(th) percentile for CDC 2000 reference) and 43% of the adolescents were normal (BMI for age between 5(th) - 85(th) percentile for CDC 2000 reference). The average energy intake, which was 1239.6+/-176.4 kcal/day, was deficient of RDA by 39%. The average protein intake was 39.5+/-7 gm/day. It was deficient by 36% and the average iron intake, which was 13.2+/-2.5 mg/day, was deficient by 48%. CONCLUSIONS: The findings reiterate the dietary deficiency among adolescent girls which adversely affects the nutritional status. If the poor nutritional status is not corrected promptly before they become pregnant, it adversely affects the reproductive outcome. If we have to meet out the goals of Reproductive and Child Health Program, intervention strategies to improve the dietary intake of adolescent girls are needed so that their requirements of energy, protein, vitamins and minerals are met. PMID- 21031107 TI - Association of adiposity with pulse pressure amongst gujarati Indian adolescents. AB - BACKGROUND AND AIM: The current study was conducted to determine the effect of adiposity on vascular distensibility in Gujarati Indian adolescents as research indicating the pathogenesis of hypertension among overweight and/or obese Indian adolescents is scant and ethnic differences exist in the pathogenesis of hypertension MATERIALS AND METHODS: A cross-sectional study was conducted on 488 Gujarati Indian adolescents of 16-19 years age group. Adiposity was assessed in terms of BMI, Body Fat %, Fat Mass, Fat Mass Index and Waist Circumference. Arterial blood pressure was recorded and pulse pressure (PP) was calculated using the standard equation based on the difference between systolic blood pressure (SBP) and diastolic blood pressure (DBP). Pearson's correlation coefficient was determined to find the association between the markers of adiposity and SBP, DBP and PP. RESULT: A significant positive correlationship was found between adiposity and PP in boys. However, no significant correlationship was found between adiposity and PP in girls. CONCLUSION: An increase in total as well as visceral adiposity is probably associated with a decrease in vascular distensibility in the Gujarati Indian adolescent boys but not in girls, thus indicating a protective role of female sex hormone estrogen which has been shown earlier to protect the vasculature from atherosclerosis, endothelial dysfunction which occurs with increase in adiposity. PMID- 21031108 TI - Study of secondhand smoke levels pre and post implementation of the comprehensive smoking ban in mumbai. AB - OBJECTIVES: This research was undertaken with the aim of assessing the indoor air quality in popular hospitality venues, as also to evaluate the effectiveness of the nationwide comprehensive public smoking ban. The analysis was split into two halves - baseline study taken up prior to implementation of the said ban on 2(nd) October 2008, and the follow-up study after it came into effect. MATERIALS AND METHODS: Twenty-five venues including five restaurants, fourteen resto-bars, two hookah (smoking water-pipe) cafes and four pubs were selected using a mix of random, convenience and purposeful sampling. Particulate matter (PM(2.5)) measurements at these venues were made using TSI SidePak AM510 Personal Aerosol Monitor. RESULTS: The average PM(2.5) level in venues where smoking was permitted prior to implementation of ban was found to be 669.95 MUg/m(3) in the baseline study. Post ban, the average PM(2.5) level in same test venues reduced to 240.8 MUg/m(3). The hookah cafes were an exception as the average PM(2.5) levels exceeded the permissible limits before as well as post ban. CONCLUSION: The baseline study showed that the hospitality venues had hazardous levels of PM(2.5) particles arising from second-hand smoke prior to smoking ban. These decreased by a maximum of 64% after the law took effect. A substantial improvement in air quality at these venues post implementation of the smoking ban indicated the effectiveness of the law. PMID- 21031109 TI - Factors Influencing Utilization of ASHA Services under NRHM in Relation to Maternal Health in Rural Lucknow. AB - BACKGROUND: Under National Rural Health Mission (NRHM), ASHA (accredited social health activist) has been identified as an effective link to address the poor utilization of maternal and child health (MCH) services by rural pregnant women. OBJECTIVE: To study the factors influencing utilization of ASHA services in relation to maternal health. STUDY DESIGN: Cross-sectional. SETTING: Primary Health Centre (PHC), Sarojininagar, Lucknow and its rural field area. STUDY PERIOD: September 2007 to August 2008. STUDY UNIT: RDW (recently delivered women) were considered as those who delivered a live newborn at PHC Sarojininagar, within a week of interview and belonged to villages within the confines of the PHC being served by ASHA. MATERIALS AND METHODS: 350 RDW were interviewed at their bedside, by a preformed and pretested schedule and then were followed-up after six weeks. RESULTS: Utilization of ASHA services for early registration was significantly associated with age and religion of RDW. Young, educated and socio economic class III RDW utilized ASHA services the maximum for early registration. Utilization of ASHA services for adequate ANC or antenatal care (100 iron and folic acid tablets, 2 tetanus toxoid injection and >=3 antenatal visits) was also inversely associated with age of RDW. Young, Hindu, scheduled caste, middle school pass, Class III RDW and those with birth order one had high odds for utilization of ASHA services for adequate ANC. With regard to postnatal check-up, again young RDW with birth order one, Hindu RDW in reference to Muslim and RDW in socio-economic class III had higher likelihood for utilization of ASHA services. Caste-wise scheduled caste (SC) and other backward caste (OBC) RDW had higher odds for utilization of ASHA services. Educated RDW and those with educated husband had higher odds for utilization of ASHA services for postnatal check-up. CONCLUSION: Young, educated RDW with low parity, educated husband and belonging to higher socio-economic class had higher odds of utilization of ASHA services. PMID- 21031110 TI - Generating an evidence base for information, education and communication needs of the community regarding deafness: a qualitative study. AB - BACKGROUND: India is a significant contributor to the world's total burden of deafness. Out of all causes, almost 50% of the causes of decreased hearing are preventable. With the launch of the National Programme for Prevention and Control of Deafness, the need for an effective information, education and communication (IEC) campaign was felt. There is negligible information available about the status of awareness levels of the community about the various aspects of hearing loss. We carried out this research with the objective of getting to know the existing awareness related to hearing loss in the community to generate an evidence base for formulating various messages to be incorporated in IEC materials for dissemination in the community. We also asked the participants about their suggestions for the various information resources so that an IEC campaign could be designed accordingly. MATERIALS AND METHODS: We carried out 10 focus group discussions among various groups of population and analyzed the discussion. RESULTS: A descriptive analysis of the observations regarding the awareness about deafness in the community and prevalent myths and suggested information resources is presented. CONCLUSION: We highlight the lacunae in the existing awareness of various causes of deafness and the preventive measures that could be taken to prevent hearing loss. The evidence generated was used to formulate relevant messages for the various target groups, which were then incorporated in development of the IEC materials for the dissemination in the community. PMID- 21031111 TI - Utilization of dental services in a field practice area in mangalore, karnataka. PMID- 21031112 TI - Lifestyle disease risk factors in a north Indian community in delhi. PMID- 21031113 TI - Sociodemographic comparison and impact of aila: the supercyclone in gosaba of west bengal. PMID- 21031114 TI - Tobacco use among rural schoolchildren of 13-15 years age group: a cross sectional study. PMID- 21031115 TI - Investigation of an outbreak of diphtheria in borborooah block of dibrugarh district, assam. PMID- 21031116 TI - Male contraception - a molecular approach. PMID- 21031117 TI - Perception of Mothers about Their Daughters Future in Rural Karnataka. PMID- 21031118 TI - Comparative risk of type 2 diabetes mellitus among vegetarians and non vegetarians. PMID- 21031119 TI - A cross-sectional study of factors influencing sex preference of a child among married women in reproductive age group in a rural area of pune, maharashtra. PMID- 21031120 TI - Intradermal cell culture rabies vaccine: a cost effective option in antirabies treatment. PMID- 21031121 TI - Awareness of Health Insurance among Inpatients at a Tertiary Care Hospital in Coastal Karnataka. PMID- 21031122 TI - Training in clinical research in India. PMID- 21031123 TI - The influence of television on children and adolescents in an urban slum. PMID- 21031124 TI - Prevalence and causes of locomotor disability in the community staying near the rural health center in goa: a community-based study. PMID- 21031125 TI - Knowledge of emergency contraception and contraceptive practices: representative study from rural uttar pradesh. PMID- 21031126 TI - A study of physical activity habits of young adults. PMID- 21031128 TI - Genetic causes of myocardial infarction: new insights from genome-wide association studies. AB - BACKGROUND: A positive family history for myocardial infarction (MI) is known to be a major cardiovascular risk factor. The current European guidelines therefore recommend intensified primary prevention for the siblings and children of persons who have had an MI. Although the genes underlying the heritable component of MI were largely unknown previously, the development of new molecular genetic methods, and particularly the advent of genome-wide association (GWA) studies, has led to the discovery of numerous genetic variants that are associated with an elevated risk of MI. METHODS: In this article, we review GWA studies on MI and coronary heart disease (CHD) that were retrieved by a selective literature search from 2007 onward. We comment on their implications for clinical practice. RESULTS: In the last three years, GWA studies have enabled the identification of many alleles that confer a higher risk of MI. A total of eleven chromosomal regions have been replicated and associated with the disease, and their functional significance has been studied. Furthermore, it has been shown that some of the manifestations of CHD, e.g., calcification, ectasia and main-stem stenosis, are more strongly inherited than others. CONCLUSION: The results of recent GWA studies for MI and CHD will aid in individual risk prediction for MI by molecular biological means. They will also permit the development of new approaches to research on the pathophysiology of myocardial infarction. PMID- 21031129 TI - Unipolar depression: diagnostic and therapeutic recommendations from the current S3/National Clinical Practice Guideline. AB - BACKGROUND: Depressive disorders are among the most common illnesses and reasons for obtaining health care. Their diagnosis and treatment are still in need of improvement. In Germany, a new S3/National Clinical Practice Guideline has been developed for this purpose. METHODS: The existing guidelines on unipolar depression from Germany and other countries were synoptically compared and supplemented with systematic literature searches. After 14 consensus conferences, a total of 107 evidence-based recommendations were issued. RESULTS: Unipolar depression should be diagnosed in accordance with ICD-10 criteria. Screening questionnaires are useful aids to diagnostic classification. When a treatment is chosen, shared decision-making with the patient is essential. Mild depressive episodes can be treated initially by watchful waiting for 14 days. For moderate depressive episodes, pharmacotherapy and psychotherapy are equally effective treatment options. For severe depression, a combination of pharmacotherapy and psychotherapy is recommended. If 4 to 6 weeks of acute therapy are insufficiently effective, lithium augmentation is recommended, rather than combination antidepressant therapy or a switch to another antidepressant. After remission, maintenance therapy should be continued for 4 to 9 months. In recurrent depression, pharmacotherapy and/or psychotherapy, where appropriate, should be continued for at least two years. Specific recommendations are given for patients who have somatic or mental comorbidities or are acutely suicidal, and recommendations are also given for coordination of care. CONCLUSION: This guideline is a comprehensive set of evidence- and consensus-based recommendations for the diagnosis and treatment of unipolar depression. An improvement in the care of patients with unipolar depression will require broad implementation of the guideline, both in the inpatient and outpatient setting. PMID- 21031130 TI - Hyponatremia. PMID- 21031131 TI - Impaired visual function. PMID- 21031133 TI - Suppression of transforming growth factor-beta effects in rabbit subconjunctival fibroblasts by activin receptor-like kinase 5 inhibitor. AB - PURPOSE: Transforming growth factor-beta (TGF-beta) activity has been implicated in subconjunctival scarring in eyes following glaucoma filtration surgery (GFS). The purpose of this study is to determine whether an inhibitor for activin receptor-like kinase (ALK) 5 (also known as TGF-beta receptor type I) could suppress TGF-beta activity and thereby promote filtering bleb survival after GFS in a rabbit model. METHODS: An ALK-5 inhibitor, SB-505124, was used. A docking study was performed to investigate the interaction between the inhibitor and the receptor. Immunofluorescence for connective tissue growth factor (CTGF) and alpha smooth muscle actin (alpha-SMA) was performed in cultured rabbit subconjunctival fibroblasts. Immunoblotting for phosphorylated Smad2 (pSmad2), CTGF, and alpha SMA was also performed. In an in vivo rabbit GFS model, SB-505124 was delivered in a lactose tablet during surgery. Eyes were examined by slit-lamp and intraocular pressure (IOP) was measured until the time of bleb failure or up to 28 days after surgery. Tissue sections on day 5 after surgery were histologically evaluated after staining with hematoxylin and eosin. The sections were also immunostained for CTGF and alpha-SMA. In addition, cell outgrowth from dissected subconjunctival tissues placed in a cell culture flask with media was investigated. RESULTS: The docking study indicated hydrogen bond interactions between SB-505124 and amino acids His-283 and Ser-280 of ALK-5. Suppression of pSmad2, CTGF, and alpha-SMA by SB-505124 was observed in cultured fibroblasts. Filtering blebs in the GFS with SB-505124 group were maintained for more than 10 days, and the period of bleb survival was significantly longer than that in controls. IOP levels after surgery seemed to be related to bleb survival. Histologically, subconjunctival cell infiltration and scarring at the surgical site in the GFS with SB-505124 and mitomycin C (MMC) groups were much subsided compared to controls. Suppression of CTGF and alpha-SMA by SB-505124 was also observed by immunofluorescence. Cell outgrowth from explants dissected from eyes to which SB-505124 was applied during GFS was robust while outgrowth was poor from those treated with MMC. CONCLUSIONS: The ALK-5 inhibitor SB-505124 was efficacious both in vitro and in vivo in suppressing the TGF-beta action. The inhibitor may provide a novel therapy for preventing ocular inflammation and scarring. PMID- 21031134 TI - Reinforcement of a minor alternative splicing event in MYO7A due to a missense mutation results in a mild form of retinopathy and deafness. AB - PURPOSE: Recessive mutations of the myosin VIIA (MYO7A) gene are reported to be responsible for both a deaf-blindness syndrome (Usher type 1B [USH1B] and atypical Usher syndrome) and nonsyndromic hearing loss (HL; Deafness, Neurosensory, Autosomal Recessive 2 [DFNB2]). The existence of DFNB2 is controversial, and often there is no relationship between the type and location of the MYO7A mutations corresponding to the USH1B and DFNB2 phenotype. We investigated the molecular determinant of a mild form of retinopathy in association with a subtle splicing modulation of MYO7A mRNA. METHODS: Affected members underwent detailed audiologic and ocular characterization. DNA samples from family members were genotyped with polymorphic microsatellite markers. Sequencing of MYO7A was performed. Endogenous lymphoid RNA analysis and a splicing minigene assay were used to study the effect of the c.1935G>A mutation. RESULTS: Funduscopy showed mild retinitis pigmentosa in adults with HL. Microsatellite analysis showed linkage to markers in the region on chromosome 11q13.5. Sequencing of MYO7A revealed a mutation in the last nucleotide of exon 16 (c.1935G>A), which corresponds to a substitution of a methionine to an isoleucine residue at amino acid 645 of the myosin VIIA. However, structural prediction of the molecular model of myosin VIIA shows that this amino acid replacement induces only minor structural changes in the immediate environment of the mutation and thus does not alter the overall native structure. We found that, although predominantly included in mature mRNA, exon 16 is in fact alternatively spliced in control cells and that the mutation at the very last position is associated with a switch toward a predominant exclusion of that exon. This observation was further supported using a splicing minigene transfection assay; the c.1935G>A mutation was found to trigger a partial impairment of the adjacent donor splice site, suggesting that the unique change at the last position of the exon is responsible for the enhanced exon exclusion in this family. CONCLUSIONS: This study shows how an exonic mutation that weakens the 5' splice site enhances a minor alternative splicing without abolishing a complete exclusion of the exon and therefore causes a less severe retinitis pigmentosa than the USH1B-associated alleles. It would be interesting to examine a possible correlation between intrafamilial phenotypic variability and the subtle variation in exon 16 inclusion, probably related to genetic background specificities. PMID- 21031135 TI - Toll-like receptor 4 contributes to retinal ischemia/reperfusion injury. AB - PURPOSE: We investigated whether retinal ischemia and inflammation produced by raising the intraocular pressure above normal systolic levels differs in mice that lack a functional toll-like receptor 4 (Tlr4) signaling pathway. METHODS: In this work we used the murine strain B6.B10ScN-Tlr4(lps-del)/JthJ, which does not express functional Tlr4. C57BL/6J was considered as the control. We induced retinal ischemia by unilateral elevation of intraocular pressure for 1 h by direct corneal cannulation. The changes in expression of proinflammatory genes 24 h postreperfusion were assessed by quantitative PCR. Corresponding changes in protein abundances were analyzed by western blot and immunohistochemistry. Cell death was evaluated by direct counting of neurons in the ganglion cell layer of flat-mounted retinas seven days postreperfusion. RESULTS: We showed that Tlr4 deficient mice display significantly reduced expression of proinflammatory genes, including RelA, tumor necrosis factor (Thf), interleukin 6 (Il6), chemokine (C-C motif) ligand 2 (Ccl2), chemokine (C-C motif) ligand 5 (Ccl5), chemokine (C-X-C motif) ligand 10 (Cxcl10), Cybb, nitric oxide synthase 2 (Nos2), and intercellular adhesion molecule 1 (Icam1) 24 h after reperfusion. The mice that lacked Tlr4 showed significantly increased survival of neurons in the ganglion cell layer following ischemic injury, as compared to wild-type controls. CONCLUSIONS: Our results indicate that Tlr4 signaling is involved in retinal damage and inflammation triggered by ischemic injury. PMID- 21031136 TI - Changes in global histone modifications during dedifferentiation in newt lens regeneration. AB - PURPOSE: Reprogramming of pigmented epithelial cells (PECs) is a decisive process in newt lens regeneration. After lens removal PECs in dorsal iris dedifferentiate and revert to stem cell-like cells, and transdifferentiate into lens cells. Our purpose is to know how global histone modifications are regulated in the reprogramming of PECs. METHODS: Iris sections were stained using various histone modification-specific antibodies. The intensity of stained signal in nucleus of PECs was measured and changes in histone modification during dedifferentiation were evaluated. RESULTS: During dedifferentiation of PECs histone modifications related to gene activation were differentially regulated. Although tri-methylated histone H3 lysine 4 (TriMeH3K4) and acetylated histone H4 (AcH4) were increased, acetylated histone H3 lysine 9 (AcH3K9) was decreased during dedifferentiation. Among all gene repression-related modifications analyzed only tri-methylated histone H3 lysine 27 (TriMeH3K27) showed a significant change. Although in the dorsal iris TriMeH3K27 was kept at same levels after lentectomy, in ventral iris it was increased. CONCLUSIONS: Histone modifications are dynamically changed during dedifferentiation of PECs. A coordination of gene activation-related modifications, increasing of TriMeH3K4 and AcH4 and decreasing of AcH3K9, as well as regulation of TriMeH3K27, could be a hallmark of chromatin regulation during newt dedifferentiation. PMID- 21031137 TI - Two mouse models for recoverin-associated autoimmune retinopathy. AB - PURPOSE: Recoverin has been demonstrated to be one of the main causative antigenic retinal proteins common in many cases of autoimmune retinopathy (AIR). Strategies for producing two different AIR mouse models associated with anti recoverin antibodies were tested. METHODS: (1) Six-week-old female B6.MRL Fal(lpr)/J mice (LPR) mice were immunized with recombinant recoverin three times at 2-4 week intervals. (2) Five-month-old Balb/cJ mice were injected with hybridoma cells designed to produce recoverin monoclonal antibodies. Anti recoverin antibodies were analyzed by immunoblot and enzyme-linked immunosorbent assay (ELISA). Electroretinograms (ERG), histopathologic examination, and flow cytometric analysis were assessed. RESULTS: High anti-recoverin antibody levels were achieved in both models, accompanied by significantly reduced scotopic and photopic responses on the ERGs. Retinal histology showed swollen cell bodies in the inner nuclear layer in recoverin-immunized LPR mice, while photoreceptor and outer nuclear layer swelling was observed in recoverin hybridoma cells injected into balb/cJ mice. Glial fibrillary acidic protein (GFAP) staining detected a marked increase of Muller cells and astrocyte reactive gliosis in both mouse models. Rhodopsin and S-opsin staining was similar to controls, while decreased numbers of bipolar cells were observed in both models. Complement component C1q and C3 deposits increased upon immunohistopathologic retinal staining in both models, while increased numbers of CD4+ and CD68+ cells from retinas were found upon flow cytometric analysis. CONCLUSIONS: These two models had similar pathology in the retina, indicating the retinal antigens to recoverin antibody set off pathologic events that include leukocyte invasion, complement deposition, reactive gliosis in the retina, and selective retinal degeneration of inner nuclear layer neurons. These two AIR mouse models will allow for detailed pathologic investigation and testing of protein antigens associated with human AIR and can be used to test treatments. It is important to note that, since most AIR patients have multiple anti-retinal antibodies, it will be possible to study which antibodies are pathologic and which have no retinal pathologic effects. These models can also serve as an important research resource for studying the pathophysiology of specific retinal proteins by creating autoantibodies, which potentially will give a better understanding of retinal protein interactions. PMID- 21031139 TI - Ultrashort Pulse Laser Ablation for Depth Profiling of Bacterial Biofilms. AB - Sample ablation by pulsed lasers is one option for removing material from a sample surface for in situ depth profiling during imaging mass spectrometry, but ablation is often limited by laser-induced damage of the remaining material. A preliminary evaluation was performed of sub-100 fs, 800 nm pulsed laser ablation for depth profiling of bacterial biofilms grown on glass by the drip flow method. Electron and optical microscopy were combined with laser desorption vacuum ultraviolet postionization mass spectrometry to analyze biofilms before and after ablation. Ultrashort laser pulses can ablate 10 - 100 um thick sections of bacterial biofilms, leaving behind a layer of lysed cells. However, mass spectra from intact and ablated biofilms doped with antibiotic are almost identical, indicating little chemical degradation by ablation. These results are consistent with prior observations from laser surgery and support the use of ultrashort pulse laser ablation for minimally disruptive depth profiling of bacterial biofilms and intact biological samples. PMID- 21031138 TI - Evidence that pneumococcal serotype replacement in Massachusetts following conjugate vaccination is now complete. AB - Invasive pneumococcal disease (IPD) has been reduced in the US following conjugate vaccination (PCV7) targeting seven pneumococcal serotypes in 2000. However, increases in IPD due to other serotypes have been observed, in particular 19A. How much this "serotype replacement" will erode the benefits of vaccination and over what timescale is unknown. We used a population genetic approach to test first whether the selective impact of vaccination could be detected in a longitudinal carriage sample, and secondly how long it persisted for following introduction of vaccine in 2000. To detect the selective impact of the vaccine we compared the serotype diversity of samples from pneumococcal carriage in Massachusetts children collected in 2001, 2004 and 2007 with others collected in the pre-vaccine era in Massachusetts, the UK and Finland. The 2004 sample was significantly (p >0.0001) more diverse than pre-vaccine samples, indicating the selective pressure of vaccination. The 2007 sample showed no significant difference in diversity from the pre-vaccine period, and exhibited similar population structure, but with different serotypes. In 2007 the carriage frequency of 19A was similar to that of the most common serotype in pre-vaccine samples. We suggest that serotype replacement involving 19A may be complete in Massachusetts due to similarities in population structure to pre-vaccine samples. These results suggest that the replacement phenomenon occurs rapidly with high vaccine coverage, and may allay concerns about future increases in disease due to 19A. For other serotypes, the future course of replacement disease remains to be determined. PMID- 21031140 TI - Alcohol Use Disorders and Depression: Protective Factors in the Development of Unique Versus Comorbid Outcomes. AB - Protective factors for young adult alcohol use disorders, depression, and comorbid alcohol use disorders and depression were examined. Participants were recruited from all fifth-grade students attending 18 Seattle elementary schools. Of the 1,053 students eligible, 808 (77%) agreed to participate. Youth were surveyed when they were 10 years-old in 1985 and followed to age 21 years years in 1996 (95% retention). Protective factors were measured at age 14 years years. Young adult disorders were assessed with the Diagnostic Interview Schedule. Alcohol refusal skills, academic skills, school and family bonding, parental rewards, school rewards, and family cohesion at age 14 years years were associated with decreased risk for comorbidity at age 21 years years. PMID- 21031141 TI - Models to Approximate the Motions of Protein Loops. AB - We approximate the loop motions of various proteins by using a coarse-grained model and the theory of rubberlike elasticity of polymer chains. The loops are considered as chains where only the first and the last residues thereof are tethered by their connections to the main structure; while within the loop, the loop residues are connected only to their sequence neighbors. We applied these approximate models to five proteins. Our approximation shows that the loop motions can usually be computed locally which shows these motions are robust and not random. But most interestingly, the new method presented here can be used to compute the likely motions of loops that are missing in the structures. PMID- 21031142 TI - Use of Recordable Compact Discs to Fabricate Electrodes for Microchip-based Analysis Systems. AB - This work demonstrates that recordable compact discs (CDs) that contain gold as a reflective layer can be used as an electrode substrate for microchip-based analysis systems. A fabrication procedure that enables the reproducible patterning of multiple electrodes has been developed. It is shown that the microelectrodes can be integrated within a PDMS-based fluidic network and used for amperometric detection of electroactive analytes at both single and dual microelectrodes. A detailed comparison is made between the CD-based patterned electrodes and electrodes made by the traditional method of sputtering gold and titanium adhesion layers onto a glass substrate. It is also shown that mercury can be electrodeposited onto a CD-based microelectrode and the amalgam electrode used to selectively detect thiols. Finally, it is demonstrated that a decoupler for microchip-based electrophoresis can be made by electrodepositing palladium onto a gold electrode and a separate downstream gold working electrode can be used for amperometric detection. These CD-based patterned electrodes are attractive alternatives for situations where device cost is of a concern or sputtering facilities are unavailable. PMID- 21031143 TI - Solvation of Biomolecules by the Soft Sticky Dipole-Quadrupole-Octupole Water Model. AB - The soft sticky dipole-quadrupole-octupole (SSDQO) potential energy function represents a water molecule by a single site with a van der Waals sphere and point multipoles. Previously, SSDQO was shown to give good properties for liquid water and solvation of simple ions and is faster than three point models. Here, SSDQO is assessed for solvating biologically relevant molecules having a multi site, partial charge description. Monte Carlo simulations of ethanol, benzene, and N-methylacetamide in SSDQO with SPC/E moments showed the water structure was as good as in SPC/E. Thus, SSDQO is potentially useful for simulations of biological macromolecules in aqueous solution. PMID- 21031144 TI - Nonparametric tests for right-censored data with biased sampling. AB - Testing the equality of two survival distributions can be difficult in a prevalent cohort study when non random sampling of subjects is involved. Due to the biased sampling scheme, independent censoring assumption is often violated. Although the issues about biased inference caused by length-biased sampling have been widely recognized in statistical, epidemiological and economical literature, there is no satisfactory solution for efficient two-sample testing. We propose an asymptotic most efficient nonparametric test by properly adjusting for length biased sampling. The test statistic is derived from a full likelihood function, and can be generalized from the two-sample test to a k-sample test. The asymptotic properties of the test statistic under the null hypothesis are derived using its asymptotic independent and identically distributed representation. We conduct extensive Monte Carlo simulations to evaluate the performance of the proposed test statistics and compare them with the conditional test and the standard logrank test for different biased sampling schemes and right-censoring mechanisms. For length-biased data, empirical studies demonstrated that the proposed test is substantially more powerful than the existing methods. For general left-truncated data, the proposed test is robust, still maintains accurate control of type I error rate, and is also more powerful than the existing methods, if the truncation patterns and right-censoring patterns are the same between the groups. We illustrate the methods using two real data examples. PMID- 21031145 TI - Gender Roles, Externalizing Behaviors, and Substance Use Among Mexican-American Adolescents. AB - A sample of 60 male and 91 female Mexican-American adolescents (age 13-18) were administered measures of positive (i.e., assertive masculinity, affective femininity) and negative (i.e., aggressive masculinity, submissive femininity) gender roles, internalizing and externalizing problem behaviors, peer substance use, and own substance use (alcohol, cigarettes, marijuana). Negative gender roles were significantly correlated with internalizing and externalizing problems for both boys and girls, with aggressive masculinity also predicting peer substance use for both genders. Assertive masculinity significantly predicted lower alcohol use in boys, and this effect was not mediated by internalizing problems, externalizing problems, or peer substance use. Negative gender roles significantly predicted higher alcohol use in girls, but this effect was almost completely mediated by internalizing problems, externalizing problems, and peer substance use. Results are discussed in terms of gender role socialization among Mexican Americans. PMID- 21031146 TI - Dynamics for Reactions of Ion Pairs in Aqueous Solution: Reactivity of Tosylate Anion Ion Paired with the Highly Destabilized 1-(4-Methylphenyl)-2,2,2 Trifluoroethyl Carbocation. AB - The sum of the rate constants for solvolysis and scrambling of carbon bridging and nonbridging oxygen-18 at 4-MeC(6)H(4)CH(CF(3))OS((18)O(2))Tos in 50/50 (v/v) trifluoroethanol/water, (k(solv) + k(iso)) = 5.4 * 10(-6) s(-1), is 50% larger than k(solv) = 3.6 * 10(-6) for the simple solvolysis reaction of the sulfonate ester. This shows that the ion pair intermediate of solvolysis undergoes significant internal return to form reactant. These data give a value of k(-1) = 1.7 * 10(10) s(-1) for internal return of the carbocation-anion pair to the substrate. This rate constant is larger than the value of k(-1) = 7 * 10(9) s(-1) reported for internal return of an ion pair between the 1-(4-methylphenyl)ethyl carbocation and pentafluorobenzoate anion to the neutral ester (4 MeC(6)H(4)CH(CH(3))O(2)CC(6)F(5)) in the same solvent. The partitioning of ion pairs to the 1-(4-methylphenyl)ethyl carbocation and to the highly destabilized 1 (4-methylphenyl)2,2,2-trifluoroethyl carbocation is compared and contrasted. PMID- 21031147 TI - The Social Dynamics of Mathematics Coursetaking in High School. AB - This study examines how high school boys' and girls' academic effort, in the form of math coursetaking, is influenced by members of their social contexts. The authors argue that adolescents' social contexts are defined, in part, by clusters of students (termed "local positions") who take courses that differentiate them from others. Using course transcript data from the recent Adolescent Health and Academic Achievement Study, the authors employ a new network algorithm to identify local positions in 78 high schools in the National Longitudinal Study of Adolescent Health. Incorporating the local positions into multilevel models of math coursetaking, the authors find that girls are highly responsive to the social norms in their local positions, which contributes to homogeneity within and heterogeneity between local positions. PMID- 21031148 TI - Generating Clinical Notes for Electronic Health Record Systems. AB - Clinical notes summarize interactions that occur between patients and healthcare providers. With adoption of electronic health record (EHR) and computer-based documentation (CBD) systems, there is a growing emphasis on structuring clinical notes to support reusing data for subsequent tasks. However, clinical documentation remains one of the most challenging areas for EHR system development and adoption. The current manuscript describes the Vanderbilt experience with implementing clinical documentation with an EHR system. Based on their experience rolling out an EHR system that supports multiple methods for clinical documentation, the authors recommend that documentation method selection be made on the basis of clinical workflow, note content standards and usability considerations, rather than on a theoretical need for structured data. PMID- 21031149 TI - Shapes of Red Blood Cells: Comparison of 3D Confocal Images with the Bilayer Couple Model. AB - Cells and organelles are shaped by the chemical and physical forces that bend cell membranes. The human red blood cell (RBC) is a model system for studying how such forces determine cell morphology. It is thought that RBCs, which are typically biconcave discoids, take the shape that minimizes their membrane bending energies, subject to the constraints of fixed area and volume. However, recently it has been hypothesized that shear elasticity arising from the membrane associated cytoskeleton (MS) is necessary to account for shapes of real RBCs, especially ones with highly curved features such as echinocytes. In this work we tested this hypothesis by following RBC shape changes using spherical harmonic series expansions of theoretical cell surfaces and those estimated from 3D confocal microscopy images of live cells. We found (i) quantitative agreement between shapes obtained from the theoretical model including the MS and real cells, (ii) that weakening the MS, by using urea (which denatures spectrin), leads to the theoretically predicted gradual decrease in spicule number of echinocytes, (iii) that the theory predicts that the MS is essential for stabilizing the discocyte morphology against changes in lipid composition, and that without it, the shape would default to the elliptocyte (a biconcave ellipsoid), (iv) that we were able to induce RBCs to adopt the predicted elliptocyte morphology by treating healthy discocytes with urea. The latter observation is consistent with the known connection between the blood disease hereditary elliptocytosis and spectrin mutations that weaken the cell cortex. We conclude that while the discocyte, in absence of shear, is indeed a minimum energy shape, its stabilization in healthy RBCs requires the MS, and that elliptocytosis can be explained based on purely mechanical considerations. PMID- 21031150 TI - Imagery Interference Diminishes in Older Adults: Age-Related Differences in the Magnitude of the Perky Effect. AB - Studies have documented the negative effects of mental imagery on perception (also known as the Perky effect) in younger adults, but imagery-interference effects in older adults have never been assessed. Two experiments examined this issue directly. Experiment 1 demonstrated that visual mental images diminish visual acuity in younger adults (mean age = 19.0) but not older adults (mean age = 73.6). Experiment 2 obtained parallel results, showing that visual imagery interfered with performance on a visual detection task in younger (mean age = 18.7) but not older adults (mean age = 66.7). Processes underlying age-related differences in imagery-interference effects are discussed and implications of these results for changes in cognitive performance in older adults are considered. PMID- 21031151 TI - Synthetic Lethality Induced by Loss of PKC delta and Mutated Ras. AB - Synthetic lethal interaction between oncogenic Ha-ras and loss of PKC has been demonstrated. Recently, the authors reported that the concurrent knockdown of PKC alpha and beta, via upregulating PKC delta, sensitizes cells with aberrant Ras signaling to apoptosis. As a continuation of the study, using shRNA, the authors demonstrate that loss of PKC delta causes a lethal reaction in NIH3T3/Hras or prostate cancer DU145 cells that overexpress JNK. In this apoptotic process, PKC alpha and beta are upregulated and then associated with RACK1 (an adaptor for activated PKC) and JNK. Immunoblotting analysis shows that JNK is phosphorylated, accompanied with caspase 8 cleavage. The inhibition of JNK abrogates this apoptotic process triggered by PKC delta knockdown. Interestingly, without blocking PKC delta, the concurrent overexpression of wt- or CAT-PKC alpha and beta is insufficient to induce apoptosis in the cells. Together with the authors' previous findings, the data suggest that PKC alpha/beta and delta function oppositely to maintain a balance that supports cells expressing v-ras to survive and prevents them from being eliminated through oncogenic stress-induced apoptosis. PMID- 21031152 TI - Flexible Cure Rate Modeling Under Latent Activation Schemes. AB - With rapid improvements in medical treatment and health care, many datasets dealing with time to relapse or death now reveal a substantial portion of patients who are cured (i.e., who never experience the event). Extended survival models called cure rate models account for the probability of a subject being cured and can be broadly classified into the classical mixture models of Berkson and Gage (BG type) or the stochastic tumor models pioneered by Yakovlev and extended to a hierarchical framework by Chen, Ibrahim, and Sinha (YCIS type). Recent developments in Bayesian hierarchical cure models have evoked significant interest regarding relationships and preferences between these two classes of models. Our present work proposes a unifying class of cure rate models that facilitates flexible hierarchical model-building while including both existing cure model classes as special cases. This unifying class enables robust modeling by accounting for uncertainty in underlying mechanisms leading to cure. Issues such as regressing on the cure fraction and propriety of the associated posterior distributions under different modeling assumptions are also discussed. Finally, we offer a simulation study and also illustrate with two datasets (on melanoma and breast cancer) that reveal our framework's ability to distinguish among underlying mechanisms that lead to relapse and cure. PMID- 21031153 TI - Active Information Selection: Visual Attention Through the Hands. AB - An important goal in studying both human intelligence and artificial intelligence is to understand how a natural or an artificial learning system deals with the uncertainty and ambiguity of the real world. For a natural intelligence system such as a human toddler, the relevant aspects in a learning environment are only those that make contact with the learner's sensory system. In real-world interactions, what the child perceives critically depends on his own actions as these actions bring information into and out of the learner's sensory field. The present analyses indicate how, in the case of a toddler playing with toys, these perception-action loops may simplify the learning environment by selecting relevant information and filtering irrelevant information. This paper reports new findings using a novel method that seeks to describe the visual learning environment from a young child's point of view and measures the visual information that a child perceives in real-time toy play with a parent. The main results are 1) what the child perceives primarily depends on his own actions but also his social partner's actions; 2) manual actions, in particular, play a critical role in creating visual experiences in which one object dominates; 3) this selecting and filtering of visual objects through the actions of the child provides more constrained and clean input that seems likely to facilitate cognitive learning processes. These findings have broad implications for how one studies and thinks about human and artificial learning systems. PMID- 21031154 TI - A DIRICHLET PROCESS MIXTURE OF HIDDEN MARKOV MODELS FOR PROTEIN STRUCTURE PREDICTION. AB - By providing new insights into the distribution of a protein's torsion angles, recent statistical models for this data have pointed the way to more efficient methods for protein structure prediction. Most current approaches have concentrated on bivariate models at a single sequence position. There is, however, considerable value in simultaneously modeling angle pairs at multiple sequence positions in a protein. One area of application for such models is in structure prediction for the highly variable loop and turn regions. Such modeling is difficult due to the fact that the number of known protein structures available to estimate these torsion angle distributions is typically small. Furthermore, the data is "sparse" in that not all proteins have angle pairs at each sequence position. We propose a new semiparametric model for the joint distributions of angle pairs at multiple sequence positions. Our model accommodates sparse data by leveraging known information about the behavior of protein secondary structure. We demonstrate our technique by predicting the torsion angles in a loop from the globin fold family. Our results show that a template-based approach can now be successfully extended to modeling the notoriously difficult loop and turn regions. PMID- 21031155 TI - Data driven computing by the morphing fast Fourier transform ensemble Kalman filter in epidemic spread simulations. AB - The FFT EnKF data assimilation method is proposed and applied to a stochastic cell simulation of an epidemic, based on the S-I-R spread model. The FFT EnKF combines spatial statistics and ensemble filtering methodologies into a localized and computationally inexpensive version of EnKF with a very small ensemble, and it is further combined with the morphing EnKF to assimilate changes in the position of the epidemic. PMID- 21031157 TI - Correlates of Spirituality among African Americans and Caribbean Blacks in the United States: Findings from the National Survey of American Life. AB - The present study examined differences in reports of spirituality among African Americans, Caribbean Blacks (Black Caribbeans), and non-Hispanic whites using data from the National Survey of American Life (NSAL). Bivariate analyses indicated that African Americans were most likely to endorse statements regarding the importance of spirituality in their lives ("How important is spirituality in your life?") and self-assessments of spirituality ("How spiritual would you say you are?"), followed by Caribbean Blacks and non-Hispanic whites. Regression analyses indicated that African Americans and Caribbean Blacks had significantly higher levels of spirituality than did non-Hispanic whites. However, there were no significant differences in spirituality between African Americans and Caribbean Blacks. Separate regression analyses for African Americans and Caribbean Blacks indicated distinctive patterns of sociodemographic and denominational correlates of spiritual sentiments. Findings are discussed in relation to available survey and ethnographic data on self-assessments of spirituality. PMID- 21031158 TI - Giffen Behavior and Subsistence Consumption. AB - This paper provides the first real-world evidence of Giffen behavior, i.e., upward sloping demand. Subsidizing the prices of dietary staples for extremely poor households in two provinces of China, we find strong evidence of Giffen behavior for rice in Hunan, and weaker evidence for wheat in Gansu. The data provide new insight into the consumption behavior of the poor, who act as though maximizing utility subject to subsistence concerns. We find that their elasticity of demand depends significantly, and nonlinearly, on the severity of their poverty. Understanding this heterogeneity is important for the effective design of welfare programs for the poor. (JEL D12, O12). PMID- 21031156 TI - Host tissue response in stem cell therapy. AB - Preclinical and clinical trials of stem cell therapy have been carried out for treating a broad spectrum of diseases using several types of adult stem cells. While encouraging therapeutic results have been obtained, much remains to be investigated regarding the best cell type to use, cell dosage, delivery route, long-term safety, clinical feasibility, and ultimately treatment cost. Logistic aspects of stem cell therapeutics remain an area that requires urgent attention from the medical community. Recent cardiovascular trial studies have demonstrated that growth factors and cytokines derived from the injected stem cells and host tissue appear to contribute largely to the observed therapeutic benefits, indicating that trophic actions rather than the multilineage potential (or stemness) of the administered stem cells may provide the underlying tissue healing power. However, the capacity for trophic factor production can be aberrantly downregulated as seen in human heart disease. Skeletal muscle is a dynamic tissue with an impressive ability to continuously respond to environmental stimuli. Indeed, a relation exists between active skeletal muscle and low cardiovascular risk, highlighting the critical link between the skeletal muscle and cardiovascular systems. Adding to this notion are recent studies showing that stem cells injected into skeletal muscle can rescue the failing rodent heart through activation of the muscle trophic factor network and mobilization of bone marrow multilineage progenitor cells. However, aging and disease can adversely affect the host tissue into which stem cells are injected. A better understanding of the host tissue response in stem cell therapy is necessary to advance the field and bridge the gap between preclinical and clinical findings. PMID- 21031159 TI - Glutamate system genes associated with ventral prefrontal and thalamic volume in pediatric obsessive-compulsive disorder. AB - This pilot study was undertaken to determine if there was a significant association between specific glutamate system genes and regional volumes of interest implicated in the pathogenesis of obsessive-compulsive disorder (OCD). Volumetric magnetic resonance imaging (MRI) and genotyping of 7 polymorphisms in two genes, glutamate receptor, ionotropic, N-methyl-d-aspartate 2B (GRIN2B) and solute linked carrier, family 1, member 1 (SLC1A1) were conducted in 31 psychotropic-naive pediatric OCD patients. The rs1805476 variant of GRIN2B was associated with left but not right orbital frontal cortex (OFC) (p=0.04) and right but not left anterior cingulate cortex (ACC) volume (p=0.02). The SLC1A1 rs3056 variant was associated with increased total (p=0.01), left (p=0.02) and right (p=0.02) thalamic volume. These results suggest that GRIN2B and SLC1A1 may be associated with regional volumetric alterations in OFC, ACC, and thalamus in children with OCD. PMID- 21031160 TI - Microglia in close vicinity of glioma cells: correlation between phenotype and metabolic alterations. AB - Microglia are immune cells within the central nervous system. In brain-developing tumors, gliomas are able to silence the defense and immune functions of microglia, a phenomenon which strongly contributes to tumor progression and treatment resistance. Being activated and highly motile, microglia infiltrate tumors and secrete macrophagic chemoattractant factors. Thereafter, the tumor cells shut down their immune properties and stimulate the microglia to release tumor growth-promoting factors. The result of such modulation is that a kind of symbiosis occurs between microglia and tumor cells, in favor of tumor growth. However, little is known about microglial phenotype and metabolic modifications in a tumoral environment. Co-cultures were performed using CHME5 microglia cells grown on collagen beads or on coverslips and placed on monolayer of C6 cells, limiting cell/cell contacts. Phagocytic behavior and expression of macrophagic and cytoskeleton markers were monitored. Respiratory properties and energetic metabolism were also studied with regard to the activated phenotype of microglia. In co-cultures, transitory modifications of microglial morphology and metabolism were observed linked to a concomitant transitory increase of phagocytic properties. Therefore, after 1 h of co-culture, microglia were activated but when longer in contact with tumor cells, phagocytic properties appear silenced. Like the behavior of the phenotype, microglial respiration showed a transitory readjustment although the mitochondria maintained their perinuclear relocation. Nevertheless, the energetic metabolism of the microglia was altered, suggesting a new energetic steady state. The results clearly indicate that like the depressed immune properties, the macrophagic and metabolic status of the microglia is quickly driven by the glioma environment, despite short initial phagocytic activation. Such findings question the possible contribution of diffusible tumor factors to the microglial metabolism. PMID- 21031161 TI - Sensory prediction or motor control? Application of marr-albus type models of cerebellar function to classical conditioning. AB - Marr-Albus adaptive filter models of the cerebellum have been applied successfully to a range of sensory and motor control problems. Here we analyze their properties when applied to classical conditioning of the nictitating membrane response in rabbits. We consider a system-level model of eyeblink conditioning based on the anatomy of the eyeblink circuitry, comprising an adaptive filter model of the cerebellum, a comparator model of the inferior olive and a linear dynamic model of the nictitating membrane plant. To our knowledge, this is the first model that explicitly includes all these principal components, in particular the motor plant that is vital for shaping and timing the behavioral response. Model assumptions and parameters were systematically investigated to disambiguate basic computational capacities of the model from features requiring tuning of properties and parameter values. Without such tuning, the model robustly reproduced a range of behaviors related to sensory prediction, by displaying appropriate trial-level associative learning effects for both single and multiple stimuli, including blocking and conditioned inhibition. In contrast, successful reproduction of the real-time motor behavior depended on appropriate specification of the plant, cerebellum and comparator models. Although some of these properties appear consistent with the system biology, fundamental questions remain about how the biological parameters are chosen if the cerebellar microcircuit applies a common computation to many distinct behavioral tasks. It is possible that the response profiles in classical conditioning of the eyeblink depend upon operant contingencies that have previously prevailed, for example in naturally occurring avoidance movements. PMID- 21031162 TI - How neuroscience and behavioral genetics improve psychiatric assessment: report on a violent murder case. AB - Despite the advances in the understanding of neural and genetic foundations of violence, the investigation of the biological bases of a mental disorder is rarely included in psychiatric evaluation of mental insanity. Here we report on a case in which cognitive neuroscience and behavioral genetics methods were applied to a psychiatric forensic evaluation conducted on a young woman, J.F., tried for a violent and impulsive murder. The defendant had a history of multidrug and alcohol abuse and non-forensic clinical evaluation concluded for a diagnosis of borderline personality disorder. We analyzed the defendant's brain structure in order to underlie possible brain structural abnormalities associated with pathological impulsivity. Voxel-based morphometry indexed a reduced gray matter volume in the left prefrontal cortex, in a region specifically associated with response inhibition. Furthermore, J.F.'s DNA was genotyped in order to identify genetic polymorphisms associated with various forms of violence and impulsive behavior. Five polymorphisms that are known to be associated with impulsivity, violence, and other severe psychiatric illnesses were identified in J.F.'s DNA. Taken together, these data provided evidence for the biological correlates of a mental disorder characterized by high impulsivity and aggressive tendencies. Our claim is that the use of neuroscience and behavioral genetics do not change the rationale underlying the determination of criminal liability, which must be based on a causal link between the mental disorder and the crime. Rather, their use is crucial in providing objective data on the biological bases of a defendant's mental disorder. PMID- 21031163 TI - Therapeutics that directly increase SMN expression to treat spinal muscular atrophy. AB - Spinal muscular atrophy (SMA) is the second most common autosomal recessive disease and is a leading cause of infantile death. This disease has a carrier frequency of 1:35, affecting 1/6,000 live births and is the result of a homozygous loss of the survival of motor neuron 1 gene (SMN1). Humans carry a nearly identical copy gene, SMN2, that codes for very low levels of the full length protein, ~10% when compared to SMN1. This is due to one silent nucleotide transition at the 5' end of exon 7 that disrupts a critical splicing regulatory domain. The underlying protein coding region, however, is unaffected by this and other nucleotide differences between SMN1 and SMN2. SMN2 has, therefore, been envisioned as an outstanding target for therapeutic strategies that 1) increases SMN2 expression, 2) alters the pre-messenger RNA splicing of exon 7 or 3) stabilizes the SMN2-derived protein products. In this review, we summarize numerous therapeutic approaches including nucleic acid-based and drug-oriented therapies that have progressed toward treating SMA. PMID- 21031164 TI - Targeting IKKbeta for the treatment of rheumatoid arthritis. AB - Activation of the nuclear factor-kappaB (NF-kappaB) family of transcription factors results in the expression of numerous genes involved in the regulation of the innate and adaptive immune responses, and has been implicated as a key mechanism in chronic inflammatory diseases including rheumatoid arthritis (RA). The IkappaB kinases (IKKs) are key components in the signaling pathway by which proinflammatory stimuli, such as lipopolysaccharide and tumor necrosis factor alpha lead to the activation of NF-kappaB. The most widely studied of the IKKs is IKKbeta. Inhibitors of the kinase activity of IKKbeta offer opportunities for intervention in RA, as well as other inflammatory disorders. Some examples for which the most extensive data are available will here be reviewed. PMID- 21031165 TI - Microfluidic probes in the treatment of brain-related diseases. AB - Many new therapeutic compounds have been developed that target malignancies and other disorders of the brain. However, delivering these compounds to diseased tissue remains a difficult challenge. One option for local drug delivery in the brain is direct infusion of the compounds through a catheter into the brain parenchyma. Over the last decade, new infusion catheters have been developed to improve this delivery method. Some of these catheters are needles or cannulas that have been modified specifically to increase the infusion rate that can be achieved without leakage of the infusate out of the brain. Other new catheters have been fabricated using micromachining techniques adapted from electronics manufacturing. These microfabricated catheters can achieve comparable infusion rates as standard needles, but they also can incorporate features that would be difficult to build into needles or cannulas to improve drug delivery. This article reviews the development of these devices, their performance in preclinical studies and their potential benefits to neural drug delivery. PMID- 21031166 TI - Prognostic and diagnostic value of des-gamma-carboxy prothrombin in liver cancer. AB - Des-gamma-carboxy prothrombin (DCP) is an abnormal prothrombin induced by the absence of vitamin K2 that is increased in the serum of patients with hepatocellular carcinoma (HCC). In hepatoma cells, genetic alterations, membrane receptors, the inability to uptake labeled low-density lipoprotein, cytoskeletal changes and hepatocyte cytoplasmic transfers involved in vitamin K metabolism could play an important role in producing detectable DCP serum levels. Serum DCP was found to have a sensitivity ranging from 48% to 62%, a specificity of 81% to 98% and a diagnostic accuracy of 59% to 84% for detecting HCC. Plasma DCP does not correlate with alpha-fetoprotein (AFP) levels. However, when used together, the DCP and AFP assays increase the sensitivity of detecting HCC in more than 85% of patients. The specificity of the DCP assay appears to be superior to that of AFP. These biomarkers can complement ultrasound for early HCC detection, but neither DCP nor AFP is optimal. For small HCC, a high preoperative DCP level appears to be indicative of tumor recurrence. Recently, there has been attention given to DCP because of its role in detecting HCC recurrence after living donor liver transplant. More recent research has demonstrated that DCP stimulates human vascular endothelial cell growth and migration. All the data presented above demonstrate the importance of DCP in formulating a prognosis for patients with HCC. PMID- 21031167 TI - Molecule of the month. Linaclotide acetate. PMID- 21031168 TI - The rise and fall of Dimebon. AB - Dimebon (latrepirdine) was developed and used in Russia as an over-the-counter oral antihistamine for allergy treatment. In the early 1990s, Dimebon was characterized as a low-affinity NMDA receptor antagonist by Dr. Sergey Bachurin and his colleagues. An initial small-scale, open-label trial of Dimebon in 14 Alzheimer's disease (AD) patients demonstrated potential efficacy. Dimebon was then patented for the treatment of neurodegenerative disorders and licensed by Medivation. Extremely promising results were obtained in a double-blind, placebo controlled, phase II AD trial in 183 patients; however, a phase II trial of Dimebon in 91 Huntington's disease patients was much less successful. Recently, a phase III AD trial of Dimebon in 598 patients failed to result in any significant improvement in primary or secondary outcomes. The failure of Dimebon may be in large part due to insufficient understanding of its mechanism of action. The NMDA receptor blocking activity of Dimebon is too weak to be physiologically relevant, while the proposed "novel mitochondrial mechanism of action" lacks credible scientific evidence or a molecular target. Independent studies indicate that the clinical effects of Dimebon most likely result from inhibition of histamine H1 and serotonin 5-HT6 receptors. Careful preclinical studies of novel potential therapies are needed to minimize chances of making similar costly mistakes in the future. PMID- 21031169 TI - Chemical & biological therapeutic approaches to neurological disorders. AB - The Royal Society of Chemistry Biotechnology Group and Chemical Biology Interface Forum held a 1-day symposium, on April 19, 2010, on Chemical and Biological Therapeutic Approaches to Neurological Disorders, at the Royal Society of Chemistry, Burlington House, London. The purpose of the meeting, organized by Colin Bedford, Irene Francois and Klaus Rumpel, was to give an update of new developments regarding the genetics, biochemistry and pathophysiology of the major neurological disorders. These developments should facilitate the discovery of better clinical biomarkers and improved medicines for the diagnosis, monitoring and treatment of patients with neurological disease. The presentations and posters covered neurological disorders including Parkinson's disease, Alzheimer's disease, multiple sclerosis, schizophrenia, autism, epilepsy and pain. The majority of these psychiatric and neurological disorders cause long term suffering and disability and thus create an important global public health problem. This was the central issue of a participative discussion that took place at the end of the meeting. PMID- 21031170 TI - Selective adsorption and chiral amplification of amino acids in vermiculite clay implications for the origin of biochirality. AB - Smectite clays are hydrated layer silicates that, like micas, occur naturally in abundance. Importantly, they have readily modifiable interlayer spaces that provide excellent sites for nanochemistry. Vermiculite is one such smectite clay and in the presence of small chain-length alkyl-NH(3)Cl ions forms sensitive, 1-D ordered model clay systems with expandable nano-pore inter-layer regions. These inter-layers readily adsorb organic molecules. n-Propyl NH(3)Cl vermiculite clay gels were used to determine the adsorption of alanine, lysine and histidine by chiral HPLC. The results show that during reaction with fresh vermiculite interlayers, significant chiral enrichment of either L- and D-enantiomers occurs depending on the amino acid. Chiral enrichment of the supernatant solutions is up to about 1% per pass. In contrast, addition to clay interlayers already reacted with amino acid solutions resulted in little or no change in D/L ratio during the time of the experiment. Adsorption of small amounts of amphiphilic organic molecules in clay inter-layers is known to produce Layer-by-Layer or Langmuir Blodgett films. Moreover atomistic simulations show that self-organization of organic species in clay interlayers is important. These non-centrosymmetric, chirally active nanofilms may cause clays to act subsequently as chiral amplifiers, concentrating organic material from dilute solution and having different adsorption energetics for D- and L-enantiomers. The additional role of clays in RNA oligomerization already postulated by Ferris and others, together with the need for the organization of amphiphilic molecules and lipids noted by Szostak and others, suggests that such chiral separation by clays in lagoonal environments at normal biological temperatures might also have played a significant role in the origin of biochirality. PMID- 21031171 TI - A single-molecule enzymatic assay in a directly accessible femtoliter droplet array. AB - The enzyme assay in a femtoliter chamber array is a simple and efficient method for concentrating the reaction product; it greatly improves the detection sensitivity down to the single-molecule level. However, in previous methods, controlling the initiation and termination of the reaction in each chamber is difficult once enclosed. Furthermore, the recovery of the enzyme and product is also difficult. To overcome these drawbacks, we developed a femtoliter droplet array in which the individual droplets are fixed on the substrate and are directly accessible from outside. A hydrophilic-in-hydrophobic micropatterned surface was used for the preparation of the droplets. When the aqueous solution on the surface is exchanged with oil, the hydrophilic surface retains the aqueous solution, and more than 10(6) dome-shaped droplets that are usable for further assay can be prepared simultaneously. The curvature radius of the droplet obeys the Young-Laplace equation, and the volume can be precisely controlled by the micropipette, which applies pressure into the droplet. Changing the pressure makes the addition, collection, and exchange of the aqueous content for individual droplets possible. Using these advantages, we successfully measured the kinetic parameters of the single-molecule enzyme beta-galactosidase and rotary motor protein F(1)-ATPase enclosed in a droplet. PMID- 21031172 TI - Surface patterning using templates: concept, properties and device applications. AB - Surface nano-patterns on substrates are the fundamental structures of various nano-devices. Template-based surface nano-patterning techniques are highly efficient methods in realizing different surface nano-patterns. The time-saving and low-cost fabrication processes of the template-based surface patterning are highly desirable for industry in fabricating different kinds of nano-devices. This tutorial review summarizes the recent advancements in the field of template based surface nano-patterning, especially focusing on three templates prepared using self-assembly processes: ultra-thin alumina membranes, monolayer polystyrene sphere arrays, and block copolymer patterns. The basic concepts, the general fabrication processes, the structure-related properties, and the device applications of these template-based surface nano-patterning techniques are introduced. PMID- 21031173 TI - Chiral interactions of histidine in a hydrated vermiculite clay. AB - Recent work shows a correlation between chiral asymmetry in non-terrestrial amino acids extracted from the Murchison meteorite and the presence of hydrous mineral phases in the meteorite [D. P. Glavin and J. P. Dworkin, Proc. Natl. Acad. Sci. U. S. A., 2009, 106, 5487-5492]. This highlights the need for sensitive experimental tests of the interactions of amino acids with clay minerals together with high level computational work. We present here the results of in situ neutron scattering experiments designed to follow amino acid adsorption on an exchanged, 1-dimensionally ordered n-propyl ammonium vermiculite clay. The vermiculite gel has a (001) d-spacing of order 5 nm at the temperature and concentration of the experiments and the d-spacing responds sensitively to changes in concentration, temperature and electronic environment. The data show that isothermal addition of D-histidine or L-histidine solutions of the same concentration leads to an anti-osmotic swelling, and shifts in the d-spacing that are different for each enantiomer. This chiral specificity, measured in situ, in real time in the neutron beam, is of interest for the question of whether clays could have played an important role in the origin of biohomochirality. PMID- 21031174 TI - Chemically-coupled-peptide-promoted virus nanoparticle templated mineralization. AB - The external surface of the plant virus Cowpea mosaic virus (CPMV) can be chemically modified with peptides that direct specific mineralization processes. Subsequent mineralization of the peptide-CPMV conjugates produces monodisperse nanoparticles of ca. 32 nm diameter coated with, for example, cobalt-platinum, iron-platinum or zinc sulfide, which cannot be readily prepared by other methods. This route is particularly attractive as it avoids the need to genetically engineer the protein surface of the virus to provide chimaeras for templated mineralization. The synthetic procedure is environmentally friendly, as it proceeds at ambient temperature and pressure, in aqueous solvent. Further, the methodology is demonstrated to be generally applicable by the mineralization of a peptide-modified multiwalled carbon nanotube. PMID- 21031175 TI - Synthetic lethal hubs associated with vincristine resistant neuroblastoma. AB - Chemotherapy of cancer experiences a number of shortcomings including development of drug resistance. This fact also holds true for neuroblastoma utilizing chemotherapeutics as vincristine. We performed a comparative analysis of molecular and cellular mechanisms associated with vincristine resistance utilizing cell line as well as human tissue data. Differential gene expression analysis revealed molecular features, processes and pathways afflicted with drug resistance mechanisms in general, and specifically with vincristine significantly involving actin associated features. However, specific mode of resistance as well as underlying genotype of parental, vincristine sensitive cells apparently exhibited significant heterogeneity. No consensus profile for vincristine resistance could be derived, but resistance-associated changes on the level of individual neuroblastoma cell lines as well as individual patient profiles became clearly evident. Based on these prerequisites we utilized the concept of synthetic lethality aimed at identifying hub proteins which when inhibited promise to induce cell death due to a synthetic lethal interaction with down regulated, chemoresistance associated features. Our screening procedure identified synthetic lethal hub proteins afflicted with actin associated processes holding synthetic lethal interactions to down-regulated features individually found in all chemoresistant cell lines tested, therefore promising an improved therapeutic window. Verification of such synthetic lethal hub candidates in human neuroblastoma tissue expression profiles indicated the feasibility of this screening approach for addressing vincristine resistance in neuroblastoma. PMID- 21031176 TI - Calorie restriction up-regulates iron and copper transport genes in Saccharomyces cerevisiae. AB - Calorie restriction (CR) is a non genetic intervention, known to confer longevity benefits across the various phyla from unicellular yeast to mammals. CR also invokes homeostatic responses similar to stress, however the sequence of molecular events leading to longevity is still illusive. In this study, we analysed the whole genome gene expression profile in response to CR, mutations mimicking CR, heat shock and H(2)O(2) from a gene ontology perspective. Our analysis revealed that mitochondrion is a common hub in the gene expression programme under these conditions and the electron transport chain (ETC) is a major player. Consequently the genes involved in the metal ion transport were also significantly up-regulated. We confirmed the results of the in silico analysis using quantitative real time PCR which showed up-regulation of genes involved in respiration and transport of iron and copper. The promoter activity of one of the representative genes, FET3, was also found to be higher upon calorie restriction. Altogether, our results indicate that upon calorie restriction the levels of iron and copper fall in cells, which elicits a transcriptional response up-regulating the genes involved in their uptake to maintain cellular homeostasis. PMID- 21031177 TI - Synthesis and characterization of aryl substituted bis(2-pyridyl)amines and their copper olefin complexes: investigation of remote steric control over olefin binding. AB - The aryl-functionalized pyridylamine 2-(i)PrC(6)H(4)N(H)py (1) and bis(2 pyridyl)amines of the type ArN(py)(2) for Ar = Mes (2), 2,6-Et(2)C(6)H(3) (3), 2 (i)PrC(6)H(4) (4), 2,6-(i)Pr(2)C(6)H(3) (5), and 1-naph (6), have been prepared by the palladium-catalyzed cross-coupling of substituted anilines with 2 bromopyridine, and have been characterized by (1)H and (13)C NMR NMR, FTIR, MS, and TGA. Complexes of these new N-aryl bis(2-pyridyl)amines have been prepared for the acid salts [H{ArN(py)(2)}]BF(4) where Ar = Mes (7) and 2-(i)PrC(6)H(4) (8), and the dimeric bridged complexes [Cu{ArN(py)(2)}(MU-X)(Y)](2) where X/Y = Cl(-) and Ar = Ph (9), 2-(i)PrC(6)H(4) (10), and 1-naph (11), in addition to X = OH(-), Y = H(2)O and Ar = Mes (12). The olefin complexes [Cu(Ar dpa)(styrene)]BF(4) for Ar = Ph (13), Mes (14), 2-(i)PrC(6)H(4) (15), and 1-naph (16), in addition to the norborylene complexes of Ar = Mes (17) and 2 (i)PrC(6)H(4) (18) have been prepared and characterized by (1)H and (13)C NMR, FTIR, and TGA. The crystal structures have been determined for compounds 1-17. Secondary amine 1 crystallizes in hydrogen-bonded head-to-tail dimers, while the N-aryl bis(2-pyridyl)amines 2-6 crystallize in a three-bladed propellar conformation, having nearly planar geometries about the amine nitrogen. The geometry about copper centers in the dimeric complexes 9-12 is distorted trigonal bypyramidal, with the axial positions occupied by one of the two pyridyl nitrogens and one of the bridging ligands (i.e., Cl or OH). The copper atoms in each of the olefin complexes 13-17 are coordinated to the two pyridine nitrogen atoms and the appropriate olefin; consistent with a pseudo three-coordinate Cu(I) cation. Distortion of pyridyl ring geometries about the copper centers, and concomitant bending of the aryl groups away from the CuN(amine) vectors were found to correlate with the steric bulk of the aryl group present in both dimeric and olefin complexes. Such distortion is also observed to a lesser extent in the acid salts as well. The (1)H and (13)C NMR spectra of [Cu(Ar-dpa)(olefin)]BF(4) exhibit an upfield shift in the olefin signal as compared to free olefin. A good correlation exists between the (1)H and (13)C NMR Deltadelta values and olefin dissociation temperatures, confirming that the shift of the olefin NMR resonances upon coordination is associated with the binding strength of the complex. PMID- 21031178 TI - Polyfluoroalkyl compounds in the aquatic environment: a review of their occurrence and fate. AB - The occurrence and fate of polyfluoroalkyl compounds (PFCs) in the aquatic environment has been recognized as one of the emerging issues in environmental chemistry. PFCs comprise a diverse group of chemicals that are widely used as processing additives during fluoropolymer production and as surfactants in consumer applications for over 50 years. PFCs are known to be persistent, bioaccumulative and have possible adverse effects on humans and wildlife. As a result, perfluorooctane sulfonate (PFOS) has been added to the persistent organic pollutants (POPs) list of the Stockholm Convention in May 2009. However, their homologues, neutral precursor compounds and new PFCs classes continue to be produced. In general, several PFCs from different classes have been detected ubiquitously in the aqueous environment while the concentrations usually range between pg and ng per litre for individual compounds. Sources of PFCs into the aqueous environment are both point sources (e.g., wastewater treatment plant effluents) and nonpoint sources (e.g., surface runoff). The detected congener composition in environmental samples depends on their physicochemical characteristics and may provide information to their sources and transport pathways. However, the dominant transport pathways of individual PFCs to remote regions have not been conclusively characterised to date. The objective of this article is to give an overview on existing knowledge of the occurrence, fate and processes of PFCs in the aquatic environment. Finally, this article identifies knowledge gaps, presents conclusions and recommendations for future work. PMID- 21031179 TI - Microplasma patterning of bonded microchannels using high-precision "injected" electrodes. AB - A rapid, high-precision method for localised plasma-treatment of bonded PDMS microchannels is demonstrated. Patterned electrodes were prepared by injection of molten gallium into preformed microchannel guides. The electrode guides were prepared without any additional fabrication steps compared to conventional microchannel fabrication. Alignment of the "injected" electrodes is precisely controlled by the photomask design, rather than positioning accuracy of alignment tools. Surface modification is detected using a fluorescent dye (Rhodamine B), revealing a well-defined micropattern with regions less than 100 um along the length of the microchannel. PMID- 21031184 TI - Melting entropy of nanocrystals: an approach from statistical physics. AB - Considering size effect on the equations obtained from statistical mechanical theories for the entropy of crystal and liquid phases, a new model has been developed for the melting entropy of nanocrystals, including the effects of the quasi-harmonic, anharmonic and electronic components of the overall melting entropy. Then with the use of our suggested new proportionality between the melting point and the entropy temperature (theta(0)), the melting entropy of nanocrystals has been obtained in terms of their melting point. Moreover, for the first time, the size-dependency of the electronic component of the overall melting entropy, arising from the change in the electronic ground-state of the nanocrystal upon melting, has been taken into account to calculate the melting entropy of nanocrystals. Through neglecting the effect of the electronic component, the present model can corroborate the previous model for size dependent melting entropy of crystals represented by Jiang and Shi. The present model has been validated by the available computer simulation results for Ag and V nanoparticles. Moreover, a fairly constant function has been introduced which couples the melting temperature, the entropy temperature and the atomic density of elements to each other. PMID- 21031185 TI - Electrochemical generation of silver acetylides from terminal alkynes with a Ag anode and integration into sequential Pd-catalysed coupling with arylboronic acids. AB - An electro-oxidative method for generating silver acetylides from acetylenes with a Ag anode was developed. The reaction could be integrated into a Pd-catalysed electrochemical Sonogashira-type reaction. In the presence of the catalytic amount of Pd(OAc)(2) and 4-BzO-TEMPO, electro-generated silver acetylides reacted immediately with arylboronic acids to afford the corresponding coupling adducts in high yields. PMID- 21031186 TI - A simple and sensitive method for visual detection of phosgene based on the aggregation of gold nanoparticles. AB - A new method with high simplicity, rapidity and sensitivity has been developed for visual detection of phosgene based on the distinct color change of cysteine modified gold nanoparticles. PMID- 21031187 TI - O-glycoligases, a new category of glycoside bond-forming mutant glycosidases, catalyse facile syntheses of isoprimeverosides. AB - A mutant alpha-xylosidase that lacks its catalytic acid/base residue efficiently catalyses the synthesis of O-linked isoprimeverosides (Xyl-alpha-1,6GlcOR) in near quantitative yields. PMID- 21031188 TI - Asymmetric total synthesis of (+)-fumimycin via 1,2-addition to ketimines. AB - The first asymmetric total synthesis of fumimycin was accomplished. As a key step, a 1,2-addition of methyl Grignard reagents to ketimines with quinine as additive was employed. The absolute configuration of (+)-fumimycin was determined by CD-spectroscopy combined with time-dependent density functional calculations. PMID- 21031189 TI - High surface area carbon aerogels as porous substrates for direct growth of carbon nanotubes. AB - Novel carbon composites are fabricated through catalyzed CVD growth of carbon nanotubes directly on the inner surfaces of monolithic carbon aerogel (CA) substrates. Uniform CNT yield is obtained throughout the internal pore volume of CA monoliths with macroscopic dimensions. These composites possess large surface areas (>1000 m(2) g(-1)) and exhibit enhanced electrical conductivity following CNT growth. PMID- 21031190 TI - Transcutaneous immunization by a solid-in-oil nanodispersion. AB - We have successfully achieved transcutaneous immunization without the use of any skin pre-treatment or immune-stimulant adjuvant by applying a solid-in-oil (S/O) nanodispersion: an oil-based nanodispersion of antigens coated with hydrophobic surfactant molecules. This finding indicates that the S/O nanodispersion has great promise for effective transcutaneous vaccination. PMID- 21031191 TI - Novel 3-D superstructures made up of SnO(2)@C core-shell nanochains for energy storage applications. AB - New 1-D SnO(2)@C core-shell nanochains built into 3-D superstructures are presented for the first time as anode materials for lithium-ion batteries. These novel SnO(2)@C core-shell nanochains exhibit desirable lithium storage properties. PMID- 21031193 TI - Characterization and mechanism study of micrometer-sized secondary assembly of beta-cyclodextrin. AB - We herein report a beta-cyclodextrin-based secondary assembly (beta-CD SA) obtained from an aqueous solution. It was found that the addition of a very small amount of organic molecule 2-phenyl-5-(4-diphenylyl) 1,3,4-oxadiazole (PBD) into an aqueous solution of 10 mM beta-CD led to the formation of a micrometer-sized rodlike SA, which made the mixture turbid immediately. After careful characterization, the structure and the formation mechanism of the beta-CD SA were suggested. PBD first induces beta-CDs to form rigid nanotubes through head to-head or tail-to-tail routes. Using the "solid" nanotubes as recrystallization centers, other beta-CDs assembled to channel in the c axis direction and hexagonally aligned in the b axis direction, leading to the formation of a beta CD SA. In the beta-CD SA, most of the beta-CDs were not occupied by PBD. In the course of formation , intermolecular hydrogen-bonding plays a prominent role. The results reported herein would be helpful in constructing cyclodextrin-based architectures in water. PMID- 21031192 TI - Detailed product analysis during the low temperature oxidation of n-butane. AB - The products obtained from the low-temperature oxidation of n-butane in a jet stirred reactor (JSR) have been analysed using two methods: gas chromatography analysis of the outlet gas and reflectron time-of-flight mass spectrometry. The mass spectrometer was combined with tunable synchrotron vacuum ultraviolet photoionization and coupled with a JSR via a molecular-beam sampling system. Experiments were performed under quasi-atmospheric pressure, for temperatures between 550 and 800 K, at a mean residence time of 6 s and with a stoichiometric n-butane/oxygen/argon mixture (composition = 4/26/70 in mol%). 36 reaction products have been quantified, including in addition to the usual oxidation products, acetic acid, hydrogen peroxide, C(1), C(2) and C(4) alkylhydroperoxides and C(4) ketohydroperoxides. Evidence of the possible formation of products (dihydrofuranes, furanones) derived from cyclic ethers has also been found. The performance of a detailed kinetic model of the literature has been assessed with the simulation of the formation of this extended range of species. These simulations have also allowed the analysis of possible pathways for the formation of some obtained products. PMID- 21031194 TI - Grand canonical ensemble molecular dynamics simulation of water solubility in polyamide-6,6. AB - Grand canonical ensemble molecular dynamics simulation is employed to calculate the solubility of water in polyamide-6,6. It is shown that performing two separate simulations, one in the polymeric phase and one in the gaseous phase, is sufficient to find the phase coexistence point. In this method, the chemical potential of water in the polymer phase is expanded as a first-order Taylor series in terms of pressure. Knowing the chemical potential of water in the polymer phase in terms of pressure, another simulation for water in the gaseous phase, in the grand canonical ensemble, is done in which the target chemical potential is set in terms of pressure in the gas phase. The phase coexistence point can easily be calculated from the results of these two independent simulations. Our calculated sorption isotherms and solubility coefficients of water in polyamide-6,6, over a wide range of temperatures and pressures, agree with experimental data. PMID- 21031195 TI - Nanomechanical architecture of semiconductor nanomembranes. AB - Semiconductor nanomembranes are single-crystal sheets with thickness ranging from 5 to 500nm. They are flexible, bondable, and mechanically ultra-compliant. They present a new platform to combine bottom-up and top-down semiconductor processing to fabricate various three-dimensional (3D) nanomechanical architectures, with an unprecedented level of control. The bottom-up part is the self-assembly, via folding, rolling, bending, curling, or other forms of shape change of the nanomembranes, with top-down patterning providing the starting point for these processes. The self-assembly to form 3D structures is driven by elastic strain relaxation. A variety of structures, including tubes, rings, coils, rolled-up "rugs", and periodic wrinkles, has been made by such self-assembly. Their geometry and unique properties suggest many potential applications. In this review, we describe the design of desired nanostructures based on continuum mechanics modelling, definition and fabrication of 2D strained nanomembranes according to the established design, and release of the 2D strained sheet into a 3D or quasi-3D object. We also describe several materials properties of nanomechanical architectures. We discuss potential applications of nanomembrane technology to implement simple and hybrid functionalities. PMID- 21031196 TI - Fibrillar superstructure from extended nanotapes formed by a collagen-stimulating peptide. AB - The nanostructure of a peptide amphiphile in commercial use in anti-wrinkle creams is investigated. The peptide contains a matrikine, collagen-stimulating, pentapeptide sequence. Self-assembly into giant nanotapes is observed and the internal structure was found to comprise bilayers parallel to the flat tape surfaces. PMID- 21031197 TI - Kinetics of bulk polymerisation and Gompertz's law. AB - The kinetics of bulk photo-polymerisation of multifunctional monomers, leading to highly cross-linked polymers, has been investigated by in situ real-time Raman spectroscopy. The decrease with time of the monomer content is described by a modified Gompertzian function originally developed for population dynamics. This function is flexible enough to take into account inhibitor effect, gel effect and glass effect which are characteristic for curing of technical polymer coatings. Layers of commercial acrylic resins with a thickness of 50 MUm, with commercial initiators, are taken as model systems for the UV-curing. The proof-of-concept is presented that the combination of Raman hardware and Gompertzian software enables systematic laboratory tests of curable systems. PMID- 21031198 TI - Soluble transition-metal nanoparticles-catalysed hydrogenation of arenes. AB - Over the last decade, the hydrogenation of arenes catalysed by soluble nanoparticles has attracted much interest from both academic and industrial research groups due to the milder conditions and the interesting selectivities achieved when compared to those obtained with classical heterogeneous catalysts. When substituted arenes are used as substrates in this reaction, the stereoselectivity is a key objective, and high levels of enantioselectivity are yet to be achieved. PMID- 21031199 TI - Highly monodisperse Cu- and Ag-based bimetallic nanocrystals for the efficient utilization of noble metals in catalysis. AB - Highly monodisperse Cu- and Ag-based bimetallic noble metal nanocrystals (BNMNs) with diameter 2-7 nm have been synthesized. The synthesis employs a successive reduction process by using inorganic metal salts as precursors at a low temperature (~110 degrees C). HRTEM, XPS and XRD analytical techniques were applied for the structural analysis of BNMNs. Catalytic activity investigation (CO oxidation) over different supports (silicate nanotubes and CeO2 nanoparticles) shows that BNMNs have identical and even enhanced performance over pure noble metal nanocrystals with similar size and size distribution, which proves that these BNMNs can significantly reduce the amount and thus make full use of noble metals in catalysis. PMID- 21031200 TI - Synthesis and hybridization properties of 2'-O-methylated oligoribonucleotides incorporating 2'-O-naphthyluridines. AB - 2'-O-(1-Naphthyl)uridine and 2'-O-(2-naphthyl)uridine were synthesized by a microwave-mediated reaction of 2,2'-anhydrouridine with naphthols. Using the 3' phosphoramidite building blocks, these 2'-O-aryluridine derivatives were incorporated into 2'-O-methylated oligoribonucleotides. Incorporation of five 2' O-(2-naphthyl)uridines into a 2'-O-methylated RNA sense strand significantly increased the thermostability of the duplex with a 2'-O-methylated RNA antisense strand. Circular dichroism spectroscopy and molecular dynamic simulation of the duplexes formed between the modified RNAs and 2'-O-methyl RNAs suggested that there are pi-pi interactions between two neighboring naphthyl groups in a sequence of the five consecutively modified nucleosides. PMID- 21031201 TI - Non-aggregated Ga(III)-phthalocyanines in the photodynamic inactivation of planktonic and biofilm cultures of pathogenic microorganisms. AB - Visible light-absorbing cationic water-soluble gallium(III) phthalocyanines (GaPcs) peripherally substituted with four and eight methylpyridyloxy groups were synthesized and investigated as antimicrobial photodynamic sensitizers. The inserted large gallium ion in the phthalocyanine ligand is axially substituted by one hydroxyl group which prevents aggregation of the complexes in aqueous solution. The cellular uptake and the photodynamic activity for the representative strains of the Gram positive bacteria methicillin-resistant Staphylococcus aureus(MRSA) and Enterococcus faecalis, of the Gram negative bacterium Pseudomonas aeruginosa and of the fungus Candida albicans in planktonic phase were studied. The tetra-methylpyridyloxy substituted GaPc1 showed lower cellular uptake compared to the octa-methylpyridyloxy substituted GaPc2. The photodynamic activity of the GaPcs was studied in comparison to methylene blue (MB) and a photodynamically active Zn(II)-phthalocyanine with the same substitution (ZnPcMe). Photodynamic treatment with 3.0 MUM GaPc1 at mild light conditions (50 J cm(-2), 60 mW cm(-2)) resulted in a high photoinactivation of the microorganisms in the planktonic phase nevertheless the dark toxicity of GaPc1 towards MRSA and E. faecalis. GaPcs against fungal biofilm grown on polymethylmethacrylate (PMMC) resin showed a complete inactivation at a higher concentration of GaPc2 (6.0 MUM) and of the referent sensitizer ZnPcMe. However, the bacterial biofilms were not susceptible to treatment of GaPcs with only 1-2 log reduction of the biofilm. The bacterial biofilm E. faecalis was effectively inactivated only with MB. The water-soluble octa-methylpyridyloxy substituted GaPc2 has a potential value for photodynamic treatment of C. albicans biofilms formed on denture acrylic resin. PMID- 21031202 TI - (51)V NMR parameters of VOCl(3): static and dynamic density functional study from the gas phase to the bulk. AB - (51)V NMR parameters have been calculated for VOCl(3), the reference compound in (51)V NMR spectroscopy, in order to capture environmental effects in both the neat liquid and the solid state. Using a combination of periodic geometry optimizations and Car-Parrinello molecular dynamics simulations with embedded cluster NMR calculations, we are able to test the ability of current computational approaches to reproduce (51)V NMR properties (isotropic shifts, anisotropic shifts and quadrupole coupling constants) in the gas, liquid and solid states, for direct comparison with liquid and solid-state experimental data. The results suggest that environmental effects in the condensed phases can be well captured by an embedded cluster approach and that the remaining discrepancy with experiment may be due to the approximate density functionals in current use. The predicted gas-to-liquid shift on the isotropic shielding constant is small, validating the common practice to use a single VOCl(3), molecule as reference in (51)V NMR computations. PMID- 21031203 TI - X-ray absorption spectroscopies: useful tools to understand metallorganic frameworks structure and reactivity. AB - The large unit cells, the enormous flexibility and variation in structural motifs of MOFs represent a big challenge in the characterization of MOF materials, particularly in cases where single crystal diffraction data are not available. In this critical review it is shown that in cases where only powder diffraction data are available additional structural information, particularly regarding local coordination within the inorganic cluster, are often mandatory in order to solve the structure. There are also cases where the inorganic cluster does not follow the symmetry of the overall structure. In such cases diffraction techniques will just "see" an average structure, missing the local structure: a lack that may be critical for understanding the specific properties of the material. In both cases, EXAFS spectroscopy is the tool that provides complementary structural information on the inorganic cluster and the way it binds to the ligand. Selected examples will show how EXAFS will be relevant in: (i) confirming the structure obtained from diffraction refinements; (ii) highlighting that the inorganic cornerstone has a lower symmetry with respect to that of the organic framework; (iii) obtaining the local structure of the inorganic cluster in the desolvated material when desolvation causes a partial loss of long range order; (iv) obtaining the local structure of the inorganic cluster in the desolvated material after coordination of a probe (or reactant) molecule, including cluster deformation upon molecule coordination and metal-molecule binding distance; (v) evidencing the presence of impurities in the form of amorphous extra-phases (339 references). PMID- 21031204 TI - Intermediates in photochemistry of Fe(III) complexes with carboxylic acids in aqueous solutions. AB - The primary processes in the photochemistry of Fe(III) complexes with carboxylic acids (glyoxalic, tartaric, pyruvic and lactic) were studied by means of laser flash photolysis. The inner-sphere electron transfer with the formation of Fe(II) complex and an escape of an organic radical to the solution bulk was shown to be a minor channel of the photolysis. The main channel was proposed to be the formation of a long-lived radical complex [Fe(II)...OOC-R](2+). Spectral and kinetic parameters of the radical complexes are determined. PMID- 21031205 TI - Field-controlled magnetic order with insulator-metal transitions in a periodic Anderson-like organic polymer. AB - The zero- and low-temperature behaviors of a quasi-one-dimensional organic polymer proposed as a symmetrical periodic Anderson-like chain model, in which the localized f orbitals hybridize with the conduction orbitals at even sites, are investigated by means of many-body Green's function theory. In the absence of magnetic field, the ground state of the system turns out to be ferrimagnetic. The temperature-induced phase diagrams have been explored, where the competition between the Hubbard repulsion U on the localized f orbital and the hybridization strength V makes an important impact on the transition temperature. In a magnetic field, it is found that a 1/3 magnetization plateau appears and two critical fields indicating the insulator-metal transitions at zero temperature emerge, which are closely related to the energy bands. Furthermore, the single-site entanglement entropy is a good indicator of quantum phase transitions. The temperature-field-induced phase diagram has also been attained, wherein the magnetization plateau state, the gapless phase and the spin polarized state are revealed. The temperature dependence of thermodynamic quantities such as the magnetization, susceptibility and specific heat are calculated to characterize the corresponding phases. It is also found that the up-spin and down-spin hole excitations are responsible for the thermodynamic properties. PMID- 21031206 TI - Water-in-oil-in-water double nanoemulsion induced by CO(2). AB - The cetyltrimethylammonium bromide (CTAB)/water/heptane emulsion system with different CO(2) pressure has been studied. The phase behavior investigation shows the nanoemulsion can be formed at suitable pressure range. The generalized indirect Fourier transformation (GIFT) analysis of the small-angle X-ray scattering (SAXS) data has drawn a clear picture of the structural information of the nanoemulsion, which reveals that the droplet of emulsion has a double structure with both the outer and inner droplet size in nanometre range. Furthermore, the investigation of the heptane/CTAB/water/CO(2) emulsion system by using electrical conductivity confirms the emulsion type transforms from O/W to W/O/W. In addition, the effect of different CTAB concentration on the nanoemulsion formation has been studied. It is found that enough CTAB concentration is necessary for the inclusion of continuous water into oil droplets. We also explored the application of the W/O/W double nanoemulsion in material synthesis. Interestingly, the hollow silica spheres with double shells were obtained in this CO(2)-induced double nanoemulsion. PMID- 21031207 TI - Photoinduced intra- and intermolecular electron transfer in solutions and in solid organized molecular assemblies. AB - The present paper highlights results of a systematic study of photoinduced electron transfer, where the fundamental aspects of the photochemistry occurring in solutions and in artificially or self-assembled molecular systems are combined and compared. In photochemical electron transfer (ET) reactions in solutions the electron donor, D, and acceptor, A, have to be or to diffuse to a short distance, which requires a high concentration of quencher molecules and/or long lifetimes of the excited donor or acceptor, which cannot always be arranged. The problem can partly be avoided by linking the donor and acceptor moieties covalently by a single bond, molecular chain or chains, or rigid bridge, forming D-A dyads. The covalent combination of porphyrin or phthalocyanine donors with an efficient electron acceptor, e.g. fullerene, has a two-fold effect on the electron transfer properties. Firstly, the electronic systems of the D-A pair result in a formation of an exciplex intermediate upon excitation both in solutions and in solid phases. The formation of the exciplex accelerates the ET rate, which was found to be as fast as >10(12) s(-1). Secondly, the total reorganization energy can be as small as 0.3 eV, even in polar solvents, which allows nanosecond lifetimes for the charge separated (CS) state. Molecular assemblies can form solid heterogeneous, but organized systems, e.g. molecular layers. This results in more complex charge separation and recombination dynamics. A distinct feature of the ET in organized assemblies is intermolecular interactions, which open a possibility for a charge migration both in the acceptor and in the donor layers, after the primary intramolecular exciplex formation and charge separation in the D-A dyad. The intramolecular ET is fast (35 ps) and efficient, but the formed interlayer CS states have lifetimes in microsecond or even second time domain. This is an important result considering possible applications. PMID- 21031208 TI - The optical activity of beta,gamma-enones in ground and excited states using circular dichroism and circularly polarized luminescence. AB - The circularly polarized luminescence (CPL) and electronic circular dichroism (CD) spectroscopic parameters corresponding to the n<-pi* and n->pi* transitions, respectively, have been calculated for selected beta,gamma-enones using density functional theory. For the smallest beta,gamma-enone, (1R,4R)-bicyclo[2.2.1]hept 5-en-2-one (norbornenone), coupled-cluster calculations have also been carried out. The excited-state potential energy surface for three of the five enones studied reveals two minima with different C[double bond, length as m dash]OC[double bond, length as m-dash]C dihedral angles, and with rotatory strengths of opposite sign. The relative energies of the minima determine the sign of the CPL intensity, which may be the same or opposite as in the CD spectrum, in agreement with experimental data. The results obtained in this first computational study of CPL demonstrate its usefulness as an indicator of excited state structures of chiral species. PMID- 21031209 TI - Vibrations of a single adsorbed organic molecule: anharmonicity matters! AB - Vibrational spectroscopy is a powerful tool to identify molecules and to characterise their chemical state. Inelastic electron tunnelling spectroscopy (IETS) combined with scanning tunnelling microscopy (STM) allows the application of vibrational analysis to a single molecule. Up to now, IETS was restricted to small species due to the complexity of vibration spectra for larger molecules. We extend the horizon of IETS for both experiment and theory by measuring the STM IETS spectra of mercaptopyridine adsorbed on the (111) surface of gold and comparing it to theoretical spectra. Such complex spectra with more than 20 lines can be reliably determined and computed leading to completely new insights. Experimentally, the vibrational spectra exhibit a dependence on the specific adsorption site of the molecules. Theoretically, this dependence is only accessible if anharmonic contributions to the interaction potentials are included. These joint experimental and theoretical advances open new perspectives for structure determination of organic adlayers. PMID- 21031210 TI - Exfoliation of hexa-peri-hexabenzocoronene in water. AB - Unsubstituted hexa-peri-hexabenzocoronene (HBC)-a small and well defined model system for graphite/graphene-was exfoliated and dissolved in water and the resulting individualized nano graphene sheets were characterized spectroscopically for the first time. PMID- 21031212 TI - Coexistence of ?3 *?3 and quasi-linear phases of sulfur adsorbed (Theta = 1/3) on a gold (111) substrate. AB - We analyze with the aid of density functional theory and molecular dynamics simulations the adsorption of sulfur (S) on a Au(111) surface at different temperatures with a variety of geometries. We have found a new superficial phase in which sulfur atoms form a quasi-linear chain with energies very close to the expected . The results suggest the coexistence of both configurations at T < 300 K. At high temperatures (T > 300 K) it was shown that the sulfur atoms have high mobility which allows their migration among different adsorption sites. At low temperatures, the mobility decreases and a thermal activation barrier of 25-30 meV can be estimated. PMID- 21031211 TI - A theoretical study of the interactions of NF(3) with neutral ambidentate electron donor and acceptor molecules. AB - A theoretical study of the complexes (dimers and trimers) formed between nitrogen trifluoride (NF(3)) and the ambidentate electron donor/acceptor systems HF, FCl, HCN, and HNC has been carried out using DFT [M05-2x/6-311++G(d,p)] and ab initio methods [(MP2/6-311++G(d,p) and MP2/aug-cc-pVTZ)]. Due to its structure, the NF(3) molecule can interact with both electron acceptors and electron donors through its N and F atoms. Thus, five minimum energy structures have been located for the dimers and four minima structures have been studied for the trimer complexes. New sigma-hole bonding complexes have been located. PMID- 21031213 TI - Activity, stability and degradation of multi walled carbon nanotube (MWCNT) supported Pt fuel cell electrocatalysts. AB - Understanding and improving durability of fuel cell catalysts are currently one of the major goals in fuel cell research. Here, we present a comparative stability study of multi walled carbon nanotube (MWCNT) and conventional carbon supported platinum nanoparticle electrocatalysts for the oxygen reduction reaction (ORR). The aim of this study was to obtain insight into the mechanisms controlling degradation, in particular the role of nanoparticle coarsening and support corrosion effects. A MWCNT-supported 20 wt.% Pt catalyst and a Vulcan XC 72R-supported 20 wt.% Pt catalyst with a BET surface area of around 150 m(2) g( 1) and with a comparable Pt mean particle size were subjected to electrode potential cycling in a "lifetime" stability regime (voltage cycles between 0.5 to 1.0 V vs. RHE) and a "start-up" stability regime (cycles between 0.5 to 1.5 V vs. RHE). Before, during and after potential cycling, the ORR activity and structural/morphological (XRD, TEM) characteristics were recorded and analyzed. Our results did not indicate any activity benefit of MWCNT support for the kinetic rate of ORR. In the "lifetime" regime, the MWCNT supported Pt catalyst showed clearly smaller electrochemically active surface area (ECSA) and mass activity losses compared to the Vulcan XC 72R supported Pt catalyst. In the "start-up" regime, Pt on MWCNT exhibited a reduced relative ECSA loss compared to Pt on Vulcan XC 72R. We directly imaged the trace of a migrating platinum particle inside a MWCNT suggesting enhanced adhesion between Pt atoms and the graphene tube walls. Our data suggests that the ECSA loss differences between the two catalysts are not controlled by particle growth. We rather conclude that over the time scale of our stability tests (10,000 potential cycles and beyond), the macroscopic ECSA loss is primarily controlled by carbon corrosion associated with Pt particle detachment and loss of electrical contact. PMID- 21031214 TI - Theoretical study of sulfur L-edge XANES of thiol protected gold nanoparticles. AB - The Scalar Relativistic-Zero Order Regular Approximation-Time Dependent Density Functional Theory has been employed to study the sulfur L-edge XANES spectrum of the [Au(25)(SCH(3))(18)](+) model cluster, with the aim to reproduce and rationalize previous experimental data. The salient experimental features are properly described by the present calculation. The model cluster contains two different types of bidentate "staple" ligand thiol fragments, and it has been possible to assign the spectral features according to the different location of the initial core orbital on one of the two different fragments. This finding suggests that in the real nanoparticle two different non-equivalent type of sulfur bidentate ligands are present, arranged with the typical staple geometry. PMID- 21031215 TI - Chemical reactions inside structured nano-environment: S(N)2 vs. E2 reactions for the F(-) + CH(3)CH(2)Cl system. AB - A new receptor for S(N)2 transition states, named NPTROL, is proposed. This molecule has a cavity and four hydroxyl groups that are able to interact with ionic S(N)2 and E2 transition states. Its catalytic effect and selectivity was investigated through high level ab initio calculations using the fluoride ion plus ethyl chloride in DMSO solution as a model system. Calculations at the ONIOM[CCSD(T)/6-311+G(2df,2p) : MP2/BASIS1] level of theory and solvent effects, included through a continuum solvation model, indicate that NPTROL is able to catalyze the S(N)2 pathway and has an inverse effect on the E2 pathway. Inside the NPTROL cavity, the DeltaG(?) for the S(N)2 transition state is 5.00 kcal mol( 1) lower than that for E2, and as a consequence this reaction becomes highly selective toward the S(N)2 product. PMID- 21031216 TI - (119)Sn MAS NMR and first-principles calculations for the investigation of disorder in stannate pyrochlores. AB - The local structure and cation disorder in Y(2)Ti(2-x)Sn(x)O(7) pyrochlores, materials proposed for the encapsulation of lanthanide- and actinide-bearing radioactive waste, is studied using (119)Sn (I = 1/2) NMR spectroscopy. NMR provides an excellent probe of disorder, as it is sensitive to the atomic scale environment without the need for any long-range periodicity. However, the complex and overlapping spectral resonances that often result can be difficult to interpret. Here, we demonstrate how (119)Sn DFT calculations can be used to aid the spectral interpretation and assignment, confirming that Sn occupies only the six-coordinate pyrochlore B site, and that the Sn chemical shift is sensitive to the number of Sn/Ti on the neighbouring B sites. Although distinct resonances are resolved experimentally when the Ti content is low, there is significant spectral overlap for Ti-rich compositions. We establish that this is a result of two competing contributions to the Sn chemical shift; an upfield shift resulting from the incorporation of the more polarizing Ti(4+) cation onto the neighbouring B sites, and a concomitant downfield shift arising from the decrease in unit cell size. Despite the considerably easier spectral acquisition, the lower resolution in the (119)Sn spectra hinders the extraction of the detailed structural information previously obtained using (89)Y NMR. However, the spectra we obtain are consistent with a random distribution of Sn/Ti on the pyrochlore B sites. Finally, we consider whether an equilibrium structure has been achieved by investigating materials that have been annealed for different durations. PMID- 21031217 TI - On multiferroicity of TTF-CA molecular crystal. AB - Magnetic properties of the TTF-CA molecular crystal below the neutral to ionic transition temperature are studied using the embedded cluster approach in combination with density functional theory. The calculated values of the Heisenberg exchange integral between the neighboring TTF and CA molecules stacked along the crystallographic axis a suggest that the ionic phase of the TTF-CA can be described as an alternating antiferromagnetic spin-1/2 Heisenberg chain with the exchange integral J = 1124 cm(-1) and the alternation parameter delta = 0.46. Although the combination of ferroelectricity of the ionic phase with the antiferromagnetic ordering renders TTF-CA multiferroic (as predicted theoretically in G. Giovannetti et al., Phys. Rev. Lett., 2009, 103, 266401), the large value of the alternation parameter should result in a nonmagnetic ground state of this phase. The dependence of the magnetic coupling parameters on the crystal structure is studied and the implications for experimental observation of magnetic properties of TTF-CA are discussed. PMID- 21031218 TI - An androgenic steroid delivery vector that imparts activity to a non-conventional platinum(II) metallo-drug. AB - A range of androgen conjugates with non-conventional platinum(II) complexes have been synthesised with the aim of targeting tumour cells since many display elevated levels of the androgen receptor. The androgenic platinum conjugates are delivered into selected cells with improved efficiency (when compared to their non-steroidal analogues). The act of conjugating an androgen to a platinum(II) complex resulted in synergistic effects between the metallic centre and the steroidal ligand, creating highly potent platinum(II) complexes from the inactive components. PMID- 21031219 TI - Conjugation of testosterone modifies the interaction of mono-functional cationic platinum(II) complexes with DNA, causing significant alterations to the DNA helix. AB - Previously a range of androgen conjugates with non-conventional platinum(II) complexes have been synthesised with the aim of enhancing cellular delivery, and which have shown increased cytotoxic activity compared with non-steroidal compounds (M. J. Hannon et al., Dalton Trans., 2010, DOI: 10.1039/c0dt00838a). To further study this, the complexes have been assessed for their ability to bind to and alter the structure of DNA. All platinum(II) complexes studied herein bind to model nucleo-bases and DNA, but to our surprise, testosterone-based complexes caused the DNA helix to undergo significant unwinding and bending, whereas non steroidal control complexes caused minimal structural alterations. These effects are similar to those cisplatin induces on DNA structure despite the fact that these compounds produce a monofunctional lesion. This ability attributed to interactions between the DNA helix and bulky steroidal skeleton of testosterone, coupled with the enhanced cellular delivery induced by the steroid make the steroid approach an exciting way to explore non-conventional platinum drug delivery. PMID- 21031220 TI - Effects of the fuel oil spilled by the Prestige tanker on reproduction parameters of wild mussel populations. AB - The aim of this work was to assess possible effects of the Prestige oil spill on reproduction parameters of mussels along the Galician and Bay of Biscay coast. Studied endpoints included sex ratio, gonad histology and vitellogenin-like proteins using the alkali-labile phosphate (ALP) method. A high prevalence of haemocytic infiltration of follicles and severe oocyte atresia was found in most localities in April 2003. Spawning gonads were observed in most impacted populations in the same sampling. In April 2004 mature small sized follicles were observed. No histopathological changes were observed in April 2005 and 2006, except a high prevalence of necrotic gametes in 6 out of 22 localities in April 2006. Female ALP levels showed high interindividual variability in April 2004, which was reduced in April 2005 and 2006. No xenoestrogenic effects were observed in male mussels. Overall, gamete alterations were detected during 2003-2004 and a recovery trend was observed afterwards. PMID- 21031222 TI - Structure and dynamics of ammonium borohydride. AB - Synchrotron powder X-ray diffraction, ab initio molecular dynamics calculations and solid state (1)H and (2)H NMR are used to refine the structure of crystalline NH(4)BH(4) including H atoms. Rapid reorientations of both ions mean that on average half-hydrogens occupy the corners of a cube around B or N. PMID- 21031221 TI - "Artificial mitotic spindle" generated by dielectrophoresis and protein micropatterning supports bidirectional transport of kinesin-coated beads. AB - The mitotic spindle is a dynamic assembly of microtubules and microtubule associated proteins that controls the directed movement of chromosomes during cell division. Because proper segregation of the duplicated genome requires that each daughter cell receives precisely one copy of each chromosome, numerous overlapping mechanisms have evolved to ensure that every chromosome is transported to the cell equator during metaphase. However, due to the inherent redundancy in this system, cellular studies using gene knockdowns or small molecule inhibitors have an inherent limit in defining the sufficiency of precise molecular mechanisms as well as quantifying aspects of their mechanical performance. Thus, there exists a need for novel experimental approaches that reconstitute important aspects of the mitotic spindle in vitro. Here, we show that by microfabricating Cr electrodes on quartz substrates and micropatterning proteins on the electrode surfaces, AC electric fields can be used to assemble opposed bundles of aligned and uniformly oriented microtubules as found in the mitotic spindle. By immobilizing microtubule ends on each electrode, analogous to anchoring at centrosomes, solutions of motor or microtubule binding proteins can be introduced and their resulting dynamics analyzed. Using this "artificial mitotic spindle" we show that beads functionalized with plus-end kinesin motors move in an oscillatory manner analogous to the movements of chromosomes and severed chromosome arms during metaphase. Hence, features of directional instability, an established characteristic of metaphase chromosome dynamics, can be reconstituted in vitro using a pair of uniformly oriented microtubule bundles and a plus-end kinesin functionalized bead. PMID- 21031223 TI - Bronsted-NH(4)(+) mechanism versus nitrite mechanism: new insight into the selective catalytic reduction of NO by NH(3). AB - The selective catalytic reduction (SCR) of NO by NH(3) over V(2)O(5)-based catalysts is used worldwide to control NO(x) emission. Understanding the mechanisms involved is vital for the rational design of more effective catalysts. Here, we have performed a systematic density functional theory (DFT) study of a SCR reaction by using cluster models. Three possible mechanisms have been considered, namely (i) a Lewis acid mechanism, (ii) a Bronsted acid mechanism and (iii) a nitrite mechanism. Our calculations down-play the significance of mechanism (i) due to its high barrier as well as the incorrect reaction order. On the other hand, our calculations demonstrate that both mechanisms (ii) and (iii) can lead to a first order reaction with respect to NO with the predicted barriers being consistent with the experimental observations. Thus, we conclude: there exists two competitive pathways for SCR. Mechanism (ii) is dominant when the Bronsted acidity of the catalysts is relatively strong, while mechanism (iii) becomes important when Bronsted acidity is weak or absent. Importantly, we demonstrate that the latter two mechanisms share a common feature where N-N bond formation is ahead of N-H bond cleavage, in contrast to that in mechanism (i). Such a sequence provides an effective way to reduce the side reaction of ammonia combustion since the relatively strong N-N bond has already been formed. PMID- 21031224 TI - Chemically reactive species remain alive inside carbon nanotubes: a density functional theory study. AB - The behavior of alkyl guest radicals inside carbon nanotube hosts with different diameters is analyzed using density functional theory (DFT) calculations. Here the inner alkyl radicals are assumed to be formed by decomposition of their precursors, which had been incorporated into the tubes. DFT calculations show that inner alkyl radicals prefer to exist separately from the nanotube wall (separate form) rather than forming an inner covalent bond with the wall (bound form). Keeping a radical apart from the inner wall is more likely for a more bulky radical inside a smaller diameter tube. A key to the preference for the separate forms over the bound forms is that the bound forms gain a weak attraction due to the formation of a bond with the inner wall. The weak attraction, ascribed to the inertness of the inner surface, is counteracted by destabilization due to deformations of a tube and radical induced by guest-host coupling. The energy balance argument illuminates that the inertness of the inner wall makes an alkyl radical species remain alive inside a tube and retain its reactivity. These findings can help us to understand experimental results where chemical reactions inside a tube proceed after guests are activated. PMID- 21031225 TI - Site specific interaction between ZnO nanoparticles and tryptophan: a first principles quantum mechanical study. AB - First principles density functional theory calculations are performed on tryptophan-ZnO nanoparticles complex in order to study site specific interactions between tryptophan and ZnO. The calculated results find the salt bridge structure involving the -COOH group and ZnO cluster to be energetically more favorable than other interacting sites, such as indole and amine groups in tryptophan. The interaction between tryptophan and ZnO appears to be mediated by both ionic and hydrogen bonds. The calculated molecular orbital energy levels and charge distributions suggest non-radiative energy transfer from an excited state of tryptophan to states associated with ZnO, which may lead to a reduction in the emission intensity assigned to the pi-pi* transition of the indole functional group of tryptophan. PMID- 21031226 TI - Synthesis and photophysics of monodisperse co-oligomers consisting of alternating thiophene and perylene bisimide. AB - A series of monodisperse oligomers consisting of alternating thiophene (T) and perylene bisimide (P), denoted as (TP)(n)T (n = 1, 2, 3, 6), were synthesized and photophysically characterized. The steady-state absorption and fluorescence spectra revealed that the low-energy P-derived band remains almost unchanged upon the increment of the number of the repeat unit n. This can be rationalized as a consequence of nearly orthogonal molecular geometry and highly-localized electron density at LUMO level based on DFT calculation. A drastic reduction of the fluorescence quantum yields (Phi(F)) of (TP)(n)T was observed with the sequence of (TP)(6)T > (TP)(3)T > (TP)(2)T > (TP)(1)T, as compared to the parent perylene bisimide. Further femtosecond transient absorption studies clarified that the quenching mechanism is intramolecular electron transfer, in which the generated P radical anion was spectrally recognized. The rate of charge separation was found to be on the order of 10(11) s(-1), suggesting an efficient electron transfer reaction between the thiophene and perylene units. Interestingly, the charge separation rate constant increased more than three times upon the increment of n, whereas the charge-recombination rate constant remained almost unchanged at (1.58 2.21) * 10(9) s(-1). Analysis of the kinetic and thermodynamic data using the Marcus approach showed that the enhanced electronic coupling is the origin of the acceleration of electron-transfer reaction in the D-A copolymers. PMID- 21031227 TI - Grating coupler integrated photodiodes for plasmon resonance based sensing. AB - In this work, we demonstrate an integrated sensor combining a grating-coupled plasmon resonance surface with a planar photodiode. Plasmon enhanced transmission is employed as a sensitive refractive index (RI) sensing mechanism. Enhanced transmission of light is monitored via the integrated photodiode by tuning the angle of incidence of a collimated beam near the sharp plasmon resonance condition. Slight changes of the effective refractive index (RI) shift the resonance angle, resulting in a change in the photocurrent. Owing to the planar sensing mechanism, the design permits a high areal density of sensing spots. In the design, absence of holes that facilitate resonant transmission of light, allows an easy-to-implement fabrication procedure and relative insensitivity to fabrication errors. Theoretical and experimental results agree well. An equivalent long-term RI noise of 6.3 * 10(-6) RIU/?Hz is obtained by using an 8 mW He-Ne laser, compared to a shot-noise limited theoretical sensitivity of 5.61 * 10(-9) RIU/?Hz. The device features full benefits of grating-coupled plasmon resonance, such as enhancement of sensitivity for non-zero azimuthal angle of incidence. Further sensitivity enhancement using balanced detection and optimal plasmon coupling conditions are discussed. PMID- 21031228 TI - [Validating Latin-American and Caribbean Latin-American food security scale on pregnant adolescents]. AB - OBJECTIVE: Statistically validating the Latin-American and Caribbean household food security scale (ELCSA) which had been linguistically adapted for Colombia during 2008 by the University of Antioquia's School of Nutrition. METHODOLOGY: This was a descriptive study. The ELCSA scale (95 % confidence interval) was applied to a representative sample of 150 households containing pregnant adolescents from poor and vulnerable populations. The pregnant girls' families were covered by ESE Salud Pereira and had consulted between April and June 2009. Four professional nurses were trained as interviewers regarding the subject of each question. 32 adult-only households and households containing 118 adults, youngsters and children were surveyed. SPSS software was used for the statistical analysis; Cronbach's alpha, factorial analysis and multiple components were used. RESULTS: ELCSA showed excellent reliability when applied to both adult-only households (Cronbach=0.927) and households having adults, teens and children (Cronbach=0.953). Factor analysis using the Kaiser-Meyer-Olkin sampling adequacy test presented high correlation amongst the items in both single adult households (p = 0.889) and households containing adults, teens and children (p=0.895). The scale's predictive ability was 75 % in the three components identified: quality and quantity of food access or availability of food and non-socially acceptable means of acquisition and distribution. CONCLUSIONS: The results validated the ELCSA scale as being a reliable tool for measuring household food security in Colombian households. PMID- 21031229 TI - [The characteristics, effectiveness and challenges of home visiting in early intervention programmes]. AB - The authors reviewed papers published between 1999 and 2009 in journals indexed in PsycInfo, PubMED, EBSCO and ProQuest concerning the characteristics, effectiveness and challenges of home visit programmes orientated towards early childhood intervention, clarifying the research's scope and limitations and its applications. Home visiting has been shown to be effective for a variety of relevant areas, especially for developing parent skills and child-caregiver relationships. The most effective programmes have started at pregnancy, lasted more than a year, had specially trained staff and have focused on building a trustworthy relationship and on modelling the infant-caregiver interaction. The importance of considering target population characteristics, the visiting model used and the visitor agent was identified in designing these programmes. In spite of the evidence accumulated in Anglo-Saxon studies, the costs associated with these programmes can be very high, thereby implying barriers which can make their dissemination difficult in Latin-American countries. The authors discuss the need for developing and evaluating other variants (i.e. including community agents), considering their cost/effectiveness ratio for treating early childhood problems, needs and characteristics in Latin-America. PMID- 21031230 TI - [The frequency of risk factors associated with obesity and being overweight in university students from Colima, Mexico]. AB - OBJECTIVE: Determining risk factor frequency regarding obesity and being overweight in university students. METHODS: A cross-sectional analytic study was carried out on 821 students from the University of Colima. Some variables analysed were age, gender, alcoholism, smoking and weight-control drug use. RESULTS: 821 students were included (380 male, 441 female), 20.9A+/-2.5 average age. 27.8 % of males were overweight and 14.7 % suffered from obesity; this was 17 % and 5.2 % in females, respectively. Smoking (2.1 OR; 1.4-3.8 95 % CI; p=0.01) and alcoholism (2.1 OR; 1.2-3.6 95 % CI; p=0.003) were associated with being overweight and being obese. Weight-control drug use was a protective factor in both genders (0.4 OR; 0.2-0.8 95 % CI; p=0.01); diet control was only a protective factor in women (2.2. OR; 1.1-3.4 95 % CI; p=0.01). CONCLUSIONS: 31.6 % of university students were overweight and suffered from obesity. Smoking and alcoholism in males were associated with being overweight and suffering from obesity. Weight-control and diet-control drug use were protective factors. PMID- 21031231 TI - [Drawing up indicators regarding success in public health programmes having a social-sports approach]. AB - OBJECTIVE: The present study was aimed at analysing how social sports projects are evaluated so as to draw up and develop indicators of success regarding social programmes' efficacy and effectiveness. METHOD: This was a descriptive survey. The sample consisted of 51 participants, male (n=29) and female (n=22), from the Nova Descoberta project whose ages ranged from 8 to 17. Data was obtained from a semi-directed survey having open items covering 10 topics; it was carried out with children and adolescents over a 2-year period (2007-2008). Documental data was also obtained from schools which had agreed to cooperate with the project. RESULTS: There were no statistically significant differences (p<0.05) between the performance of survey group participants and those who had not joined the project in terms of scholastic performance during 2007. A significant difference (p<0.05) was observed regarding studying Portuguese when comparing the groups having the highest averages being obtained by students who joined in 2008. DISCUSSION: A series of indicators contributing towards reliable evaluation emerged within the social context regarding sports projects. The manifestation of other characteristics in the environment could have interfered with participation and involvement in physical activity and, consequently, with the children and adolescents' health and quality of life. CONCLUSION: It was found that school work performance indicators could be taken together with other indicators, such as development of various abilities, participation in other activities, activity motivation, behaviour and attitudes at home and at school, for evaluating social projects. PMID- 21031232 TI - [Patients attended at a Venezuelan Toxicology Centre]. AB - OBJECTIVE: Characterising patients attended at a toxicological centre in the central western area of Venezuela (the state of Lara). METHODS: This was a descriptive/cross-sectional study. The population consisted of 1,938 patients who registered during 2006 and 2007; data was collected from the Centre's data collection forms. RESULTS: 57.4 % of the patients recorded on the toxicological centre's forms during 2006 and 2007 consulted during 2006. The patients' average age was 19 during 2006 (including adults and teenagers) and 20 during 2007. Males most often attended the centre (55.4 %). The most common cause for consultation was poisoning from snake bite, more than 40 % of the cases being caused by Bothrops. Pesticide intoxication was the second cause for male consultation (20.6 %); female medication poisoning accounted for 26.6 %. Iribarren County had the highest consultation rate in the State of Lara (47.8 % of cases). 95 patients (4.9 %) came from neighbouring States (Portuguesa and Yaracuy) during the two years this study lasted. CONCLUSIONS: It is hoped that this study will lead to special education and attention programmes for the most commonly diagnosed pathologies being implemented with greater frequency, as well as corrective action being taken regarding individual and collective risk in the state of Lara's different geographical areas. PMID- 21031233 TI - [The prevalence of happiness in life-cycles and regarding support networks in the Colombian population]. AB - OBJECTIVE: Assessing the relationship between happiness and social support networks in Colombia. METHODOLOGY: A cross-sectional, observational study was carried out on 7,335 people living in an urban area (Bogota) and a rural area (Ubate) who had been stratified by age, economic status and last year of schooling. A questionnaire asked about the people's perception of their current mood and how they received support when they had problems. RESULTS: Average age was 31; 31 % perceived that they were happy. God provided the greatest support (91 % prevalence), followed by oneself (77 %), a friend (60 %), mother (57 %) and a brother/sister (50 %). The greater the support network, the greater the amount of perceived happiness (66 OR; 5-9 95%CI). CONCLUSIONS: A strong relationship between happiness and social support networks promotes people's well being. PMID- 21031234 TI - [Smoking and student survival at Universidad Santiago de Cali, 2004-2007]. AB - OBJECTIVE: This article presents the results of monitoring students who enrolled at Universidad Santiago de Cali (USC) during the second half of 2004. Its purpose was to determine the influence of smoking, the academic programme and the cost of enrollment on student survival over a three-year period (2004-2007). METHOD: The study involved a prospective cohort of 970 students who entered the university in 2004. Cox regression was used for survival analysis to determine the relationship between independent variables and university stay. RESULTS: The results of this model established associations between smoking and department with survival in the university, but discarded association with the cost of enrollment. The risk of university desertion was higher amongst students from the Health faculty adjusted for smoking (RR = 1.277 (1.121-1.455)). Similarly, the risk of desertion was higher in smokers adjusted by faculty (RR = 1.194 (1.026-1.390). CONCLUSIONS: It was found that habitual smokers had shorter university stay than nonsmokers. University stay was longer in students enrolled in academic programmes other than health. PMID- 21031235 TI - [Cardiovascular risk factor prevalence in civil aviation pilots in Colombia during 2005]. AB - OBJECTIVE: The human-flying machine interface relies heavily on flight safety. Coronary disease is the most commonly occurring sudden incapacitation during flight and involves factors described as leading to cardiovascular risk. Pilots probably have risk prevalence different to the rest of the population. METHOD: This was a descriptive cross-sectional study. Medical histories from January to December 2005 for pilots certified by the Colombian Civil Aeronautic society were reviewed; these were randomly selected until 614 histories were obtained. A 95 % confidence level and 0.5 % accuracy level were used. Data was obtained regarding age, blood pressure, tobacco use, cholesterol, glycaemia, physical fitness, past history, gender, height, flying time and type of licence. STATG 6 software was used for analysing the data and the results were expressed as descriptive statistics. RESULTS: Percentage risk factor prevalence in pilots was as follows: 7.8 % suffered hypertension, 1.3 % diabetes, 36 % hypercholesterolemia, 36 % hypertriglyceridaemia, 36 % had low HDL, 32 % high LDL, 12.8 % tobacco use, 7 % were obese and 6 % suffered from metabolic syndrome. There were differences between pilots holding first and second class licences, more prevalent risks occurring amongst second class pilots. CONCLUSION: The prevalence of risk factors differs between pilots and the general population. According to the Framingham scale, 8 % of the pilots were in the high risk group so they require specific programmes and strict follow-up for modifying the risk profile and improving flight safety. PMID- 21031236 TI - [Primary central nervous system tumours reported in Cartagena, 2001-2006]. AB - OBJECTIVES: Determining the frequency of primary central nervous system tumours diagnosed in Cartagena; Colombia, from 2001-2006 and determining the demographic, epidemiological and clinical characteristics of patients having central nervous system tumours reported by a single institution in Cartagena between 2001 and 2006. METHODS: A passive epidemiological surveillance descriptive study was carried out. The pathology reports of new diagnosed central nervous system primary tumours from all laboratories in Cartagena were taken and the available clinical records regarding these cases were analysed. The overall incidence rate and incidence rates by year, gender, age and histological type were estimated, with 95 % confidence intervals. Standardised morbidity rates were also calculated. RESULTS: There were 390 such cases during 2001-2006. The overall incidence rate was 6.91/100,000 people-year. Meningiomas were the most frequently occurring histological types (3.46/100,000 people-year). The provenance could only be determined in 43.1 % of cases. Standardised morbidity rates were higher in Cartagena regarding those reported in the United States and by the Colombian National Cancer Institute and the Population-based Cali Cancer Registry. CONCLUSIONS: There was a higher incidence of primary central nervous system tumours in Cartagena than in the rest of the country. Registry and surveillance systems should be improved and research into risk factors encouraged. PMID- 21031237 TI - [The prevalence of antibodies against Leptospira in urban human and canine populations from the Tolima Department]. AB - OBJECTIVE: Determining Leptospira sp. antibody seroprevalence and prevalent serovars in human and canine populations from three municipalities in the Tolima Department of Colombia. MATERIALS AND METHODS: This was a cross-sectional study (subjects being selected by convenience sampling in 62 districts). Samples were collected from 850 dogs and 850 people during June, July and August 2007; these were processed using a microscopic agglutination test (MAT) and five serovars: Hardjo, Pomona, Grippotyphosa, Canicola, Icterohaemorrhagiae and Bratislava. MAT was considered positive when 50 % or more leptospira were agglutinated with one or more serovars in a 1:100 serum dilution in both species. RESULTS: At least one serovar showed evidence of infection in 6 % of the people and 21.4 % of canines. The most prevalent serovars were Pomona and Grippotyphosa in two populations. Co agglutinations were present in 49 % of human sera and 19.2 % of canine samples. Decreased Canicola and Icterohaemorrhagiae serovar agglutination frequency was evident in dogs. CONCLUSIONS: There was a change in leptospirosis pattern in urban populations. Active and passive surveillance must be strengthened, routine diagnostic tests implemented and preventative measures taken in specific animal reservoirs. PMID- 21031238 TI - Dynamic among periodontal disease, stress, and adverse pregnancy outcomes. AB - OBJECTIVE: The aim of this study was to determine the dynamic between periodontitis and stress and the incidence of preterm birth (PTB), low birth weight (LBW) and preterm low birth weight (PLBW) in pregnant women from Pasto, Narino, Colombia. METHODS: Forty-six women who attended to "Hospital Local Civil" localized in the city were involved. Periodontal clinical evaluation, pregnancy outcome variables and a stress scale were collected. Data were analyzed using descriptive and analytic statistics. RESULTS: The incidence of PTB was 13 %, of LBW was 4.3 %, and the occurrence of PLBW was 21.7 %. Our findings showed that the presence of periodontitis and stress all together increase the risk of LBW babies (OR=4.6; 95 % CI: 0.2-86.6). Regarding, periodontitis and stress interaction, the risk of PTB (OR=0.9; 95 % CI: 0.08-9.6) and PLBW (OR=1.1; 95 % CI: 0.1-7.1) decreased in the presence of these two variables, although their values were higher in the absent of stress (PTB, OR=2.3; 95 % CI: 0.3- 14.7 and PLBW, OR=10.3; 95 % CI:1.1-93.2). CONCLUSIONS: The periodontal disease in this study was associated with PTB, LBW and PLBW. However, their risk depends on the physiological changes produced by stress. PMID- 21031239 TI - [Potentially inappropriate medication in elderly in a first level hospital, Bogota 2007]. AB - OBJECTIVE: To describe the potentially inappropriate medications in the elderly (PIME) treated at outpatient consultation in the first level in Bogota in 2007. METHODOLOGY: A cross sectional study was developed, updated in 2002 Beers criteria were used as PIME. The information was obtained from a random sample of 423 outpatients older than 65 years attending at 16 primary care units, reviewing last recorded in year in the clinical history. RESULTS: The average number of drugs prescribed was 3,017, 71.9 % of the patients were on polymedication. Drug groups more frequently prescribed were those acting on cardiovascular (33.9 %), alimentary tract and metabolism (17.6 %) and musculoskeletal (10.6 %) system. According to the Beers criteria 21.5 % of patients received PIME. There was an association of polypharmacy with PIME. PIME was more frequent in patients with diagnoses of musculoskeletal and circulatory system diseases and drugs prescription with action on the musculoskeletal, nervous and respiratory system. Drugs that can cause problems not classified as PIME by Beers were prescribed to 25.1 % of patients. CONCLUSIONS: The PIME is a frequent problem, it is necessary to adapt and complement the Beers criteria to local situation, and beside to describe the PIME is necessary to study its causes. PMID- 21031240 TI - [Water pollution caused by pesticides in an area of Antioquia]. AB - OBJECTIVE: Determining the frequency of pesticide use in agricultural, pig and poultry production to understand its influence on water resources in the village of Monterredondo in the municipality of San Pedro de Los Milagros (Antioquia) and diagnosing its quality. METHODS: 100 % of the households in the village were surveyed regarding chemical use. Physicochemical and microbiological analysis of three water samples was carried out in the Universidad de Antioquia's Environmental Engineering laboratory using standardised methods. RESULTS: The Hato stream was contaminated by 1,600 x 103 NMP/100ml coliforms and 220 x 10 NMP/100 ml E. coli. The Fray Juana stream had 1,600 x 103 NMP/100ml coliform contamination. Water sources were also contaminated by the use of pesticides such as Lorsban (chlorpyriphs), Burst (chlorpyriphs), Whip (chlorpyriphs), Neguvon (metriphonate) and Furadan (carbophuran) and insecticides like Ganabano (cypermethryn) and disinfectants and Limpido (6 % sodium hypochlorite). CONCLUSION: Agricultural, pig and poultry production in the village has been producing a negative impact on water resources due to its reduced availability and pollution. The water from the samples analysed here was not suitable for human consumption. PMID- 21031241 TI - [A mathematical model representing HIV/AIDS transmission dynamics in a sexually active population]. AB - This article presents a new model explaining acquired immunodeficiency syndrome (AIDS) transmission dynamics amongst heterosexually active couples. It covers the assumptions made, the variables analysed, the model's sensitivity and the ordinary differential equations and control strategies used. The information was obtained from the Colombian state Statistics Department (DANE) and applied to different simulations in the system (with and without control), using the MAPLE programme code. Simulation results led to concluding that control using condoms was relevant in the model. It was not important if control were applied in women or men, nor was the percentage of sexually-active men and women. PMID- 21031242 TI - [A model of congenital toxoplasmosis transmission dynamics]. AB - Toxoplasmosis is a parasitic zoonosis having worldwide distribution; it infects many human and animal populations and is produced by the parasite Toxoplasma gondii, this being of great importance in contagion of pregnant women since this zoonosis causes illness in the fetus through transplacental infection. A constant mother-foetus infection rate has traditionally been used. Nevertheless, there is evidence of a strong relationship between a mother's gestation week and the moment when a foetus becomes infected. This work describes congenital toxoplasmosis transmission dynamics by using an age-structured model taking a mother's gestational week into account. The model was adapted to a space-time model describing T. gondii dispersion through cats; this provided the amount of parasites in the environment depending on which a pregnant woman would become infected. Simulations were done, varying the amount of parasites and the pregnant mother-inoculum distance. Some parameters related to possible control measures were also varied. Important changes were found when comparing infected pregnant female population patterns, when a constant mother-fetus infection rate was used and when a dependent pregnancy week rate was used. This led to concluding that the gestation week in which the mothers became infected is fundamental in infection being transmitted to their fetuses. PMID- 21031243 TI - [The relevance of urban environments and physical activity in older adults for Latin-America]. AB - Aging in Latin-America has been characterised by its rapid pace which, in turn, has been accompanied by growing urbanisation and globalisation. These processes have been linked to the prevalence of physical inactivity thereby contributing to the appearance of chronic diseases, these being the primary cause of mortality in the region. The influence of public urban environment intervention policy on physical activity has been emphasised recently. This evidence comes mainly from studies conducted in the USA and Australia. However, this topic has scarcely been studied in Latin-America which has particular characteristics regarding aging and urban development. Cities, such as Curitiba and Bogota, have undergone significant urban changes which may be linked to physical activity and the quality of life, especially in older adults. Considering the particularities of urban development in Latin-America, it is thus concluded that multidisciplinary studies should be carried out thereby leading to better understanding of the links between urban environments and physical activity in older adults. PMID- 21031244 TI - [Reproducibility of histopathologic diagnosis of precursor lesions of gastric carcinoma in three Latin American countries]. AB - OBJECTIVE: The aim was to evaluate the concordance in the diagnosis of precursor lesions of intestinal-type gastric carcinoma among observers with different levels of experience. MATERIAL AND METHODS: Gastric biopsies from 1 056 cases were studied: 341 from Colombia, 382 from Mexico, and 333 from Paraguay. Pathologists without experience (A) and with experience (B) in gastrointestinal pathology, as well as experts working in an international reference center (C) participated in the diagnosis of each case. RESULTS: The concordance (k) between pathologists with experience and those without was poor for the diagnosis of atrophic gastritis (k=0.04 to 0.12) and dysplasia (k=0.11 to 0.05), and good for the diagnosis of intestinal metaplasia (k=0.52 to 0.58). Supervision of pathologists without experience by those with experience remarkably improved the concordance in the diagnosis of atrophic gastritis (k=0.65) and intestinal metaplasia (k=0.91), and to a lesser degree, of dysplasia (k=0.28). The concordance among experts before and after the consensus meeting showed no variation in the diagnosis of atrophic gastritis (k=0.57); the concordance varied from good to excellent in the diagnosis of intestinal metaplasia (k=0.67 to 0.81) and from poor to good in that of dysplasia (k=0.18 to 0.66). CONCLUSION: The greatest differences arose in the diagnosis of chronic atrophic gastritis and dysplasia. The interobserver concordance depended on the experience of the observer and the consensus reading. PMID- 21031245 TI - Invasive pneumococcal disease in a third level pediatric hospital in Mexico City: epidemiology and mortality risk factors. AB - OBJECTIVE: To assess the epidemiologic characteristics of invasive pneumococcal diseases (IPD) among a population in a pediatric hospital in Mexico City and analyze mortality-related risk factors, serotype distribution and antibiotic susceptibility related to S.pneumoniae. MATERIAL AND METHODS: We performed a retrospective review of IPD cases at a third level pediatric hospital between 1997-2004. RESULTS: A total of 156 patients were included. The mortality rate was 27.5% and was associated with six pneumococcal serotypes: 14, 6B, 23F, 6A, 19F and 19A. There was no relationship between mortality and antimicrobial susceptibility pattern. A total of 28.2% of isolates were resistant to penicillin and 24.6% were resistant to cefotaxime. A statistically significant relationship was observed between mortality and previous underlying disease (CI 95%; 2.5-18.3; p< 0.05) using a multivariate logistic regression model. CONCLUSIONS: Our outcomes show that IPD mortality in our population is closely related to underlying disease and to six serotypes, five of which are included in the 7 valent pneumococcal conjugate vaccine. PMID- 21031246 TI - The effect of exercise on cardiovascular risk markers in Mexican school-aged children: comparison between two structured group routines. AB - OBJECTIVE: To assess the effects of two groups of exercise routines on cardiovascular disease risk markers. MATERIAL AND METHODS: An intervention study was conducted with 319 Mexican school-aged children in which routines were implemented Monday through Friday for 12 weeks. Routine A was the reference group, with 20 min of less intense activity and routine B was the new group with 40 min of aerobic exercises. Body mass index (BMI), waist circumference, fat mass percentage (FM%), systolic and diastolic blood pressure, lipids, lipoproteins, glucose and insulin were measured before and after the intervention. RESULTS: Routine A had an effect on diastolic pressure, while routine B had an effect on BMI, FM%, blood pressure and triglycerides. Routine B had a greater effect on blood pressure than routine A. The prevalence of obesity, high blood pressure and hypertriglyceridemia decreased in both groups. CONCLUSION: Aerobic exercise is an effective health promotion strategy to reduce some cardiovascular disease risk markers. PMID- 21031247 TI - [Psychosocial correlations of the experimentation with psychoactive substances in Spanish teenagers]. AB - OBJECTIVE: To offer an analysis of the factors that determine the consumption of psychoactive substances by youth and to evaluate the predictive capacity of variables related to attitude, affect, the family and groups, as well as academics, among others. MATERIALS AND METHODS: A sample of 750 adolescents was selected at the Principado de Asturias (Spain) (mode 15 years of age, mean=14.69) enrolled during the 2008-2009 academic year. RESULTS: It was confirmed that the teenagers who consumed alcohol and other drugs present a differential profile as compared to non-consumers with respect to greater attitudinal permissiveness, effect of paternal modelling and peer groups, institutional dissatisfaction, emotional instability, and manifestation of more disruptive conducts with problems relating to others and attention-seeking. CONCLUSIONS: From our ethiological model we conclude that the consumption of drugs by youth is determined by an interrelation of personal, familiar, school and psychosocial variables. PMID- 21031248 TI - [Factors associated with the demand for delivery care in Mexico]. AB - OBJECTIVE: Analyze the factors associated with the utilization of delivery care institutions in Mexico in order to document the functional integration of health institutions. MATERIALS AND METHODS: Based on the 2006 National Health and Nutrition Survey, information from women whose last birth was between 2000 and 2005 was used. Chi square was used to test differences between institutions used and health insurance type. A logistic regression was carried out to identify factors associated with the demand for institutions with which women were not affiliated. RESULTS: Women with social security used in 62% of the cases the institution of their affiliation and 13.4% used public institutions. For uninsured women, 43.3% used public institutions and 19.0% social security institutions; 64.3% of the Seguro Popular affiliates were treated in public institutions. Variables related to access, socioeconomic status and living conditions influenced said demand. CONCLUSIONS: The utilization of an institution of delivery that differed from the one with which the women were affiliated indicates the existence of a de facto functional integration between health institutions in Mexico. PMID- 21031249 TI - [Health services in the Mixteca: use and conditions of affiliation in US-migrant and non-migrant households]. AB - OBJECTIVE: To describe the socioeconomic and demographic characteristics of households in the Mixteca Baja and analyze differences in affiliation with health care programs and utilization, among members of households with migrants (HogMig) and without migrants (HogNoMig) to the United States. MATERIAL AND METHODS: A cross-sectional, descriptive survey was used with heads of households in a representative sample from the Mixteca Baja of 702 homes with and without migrants to the US. RESULTS: Members of HogMig had more personal and economic resources than those of HogNoMig; they also regularly received remittances. The majority of members of both HogMig and HogNoMig did not receive benefits from the Oportunidades program or health coverage through Seguro Popular, IMSS or ISSSTE. In general, while they used the local health clinic, they often preferred to pay for private practitioners. A small proportion of those covered by IMSS or ISSSTE reported very low utilization of the health services offered by those institutions. PMID- 21031250 TI - [Automated geospatial model for health services strategic planning]. AB - OBJECTIVE: To develop an automated model for the operational regionalization needed in the planning of the health service networks proposed by the new Mexican health care model (Modelo Integrador de Servicios de Salud MIDAS). MATERIAL AND METHODS: Using available data for Mexico during 2005 and 2007, a geospatial model was developed to estimate potential catchment areas around health facilities based on access travel time. The results were compared with an operational regionalization (ERO) study manually carried out in Oaxaca with 2005 data. RESULTS: The ERO assigned 48% of villages to health care centers further away than those assigned by the geospatial model, and 23% of these health centers referred patients to more distant hospitals. CONCLUSIONS: The model calculated by this study generated a more efficient regionalization than the ERO model, minimizing travel time to access health services. This model has been adopted by the General Department of Health Planning and Development of the Mexican Ministry of Health for the implementation of the Health Sector Infrastructure Master Plan. PMID- 21031251 TI - [Toll-like receptors, pathogenesis and immune response to Helicobacter pylori]. AB - Helicobacter pylori colonize the gastric epithelial, most infected people are asymptomatic, 10 to 20% develop atrophic gastritis, peptic ulcer and less than 3% gastric cancer. These diseases are determined by the relationship between virulence factors of bacteria, host factors such as, genetic predisposition, and immune response. The innate immune response mainly represented by Toll-like receptors and Nod-like receptors that recognize their specific ligands, activate transcription factors as NF-kB, AP-1, CREB-1, inducing production of inflammatory cytokines such as IL -8, IL-12, IL-6, IL-1beta, IL-18, TNF-alpha and IL-10. Chronic inflammation promotes gastric morphological changes, prevents apoptosis and allows angiogenesis generating neoplasic lesions and cancer. The aim of this review is to analyze the mechanisms proposed to date of the innate and adaptative immune response involved in H. pylori infection; remarking the mechanisms related in the elimination or persistence. PMID- 21031252 TI - [Food and health, a conflictive relationship: the case of Spain]. AB - This study analyzes the factors that have triggered a gradual deterioration of eating habits and the new social and cultural imperatives that have seriously undermined the well-being of Spanish consumers. It shows that consumption of basic food products to ensure good nutrition has declined, while consumption of unhealthy food products has increased. The consumption of cereals, rice, legumes and wine has significantly declined; meat, milk, dairy products and fat consumption has substantially increased. Moreover, eating habits have changed and diversified, adapting to new constraints imposed by an increasingly industrialized society. Conclusions and recommendations for acquiring healthy eating habits are presented at the end of the paper. PMID- 21031258 TI - Plasmid-encoded multidrug resistance: A case study of Salmonella and Shigella from enteric diarrhea sources among humans. AB - Salmonellosis and shigellosis are significant and persistent causes of diarrheal diseases among humans in developing countries. With that in mind, the current study investigates the occurrence of plasmid-encoded multidrug resistances in Salmonella and Shigella from diarrheal cases among humans. The isolates were characterized by serotyping, antimicrobial-susceptibility testing, transfer experiments and curing. The extended spectrum beta-lactamase (ESBL) was detected by the double disc diffusion synergy test (DDST). A significant number of the plasmid-encoded multidrug resistant (PEMDR) Salmonella and Shigella isolates were found to harbour transferable plasmid genes resistant to antibiotics like ampicillin, chloramphenicol, trimethoprim-sulfamethoxazole, ceftriaxone, cefuroxime and to a lesser extent to ciprofloxacin and ofloxacin. The conjugative R-plasmids-encoded extended-spectrum beta-lactamase also showed resistances to cephalosporins (ceftriaxone and cefuroxime) and ampicillin. Curing experiments showed chromosomal resistances to varied antibiotics. The findings confirmed the presence of PEMDR in Salmonella and Shigella strains as a suitable adaptation to a changing antibiotic environment. The results therefore suggest the limited use of the commonly prescribed/or third generation cephalosporins as an empirical treatment of multidrug resistant Salmonella and Shigella because this may affect therapeutic outcomes. PMID- 21031253 TI - [Fumonisin intake and human health]. AB - Fumonisins are mycotoxins that contaminate maize, disrupt the folate and sphingolipid metabolism, are associated with neural tube defects, and are considered by the International Agency for Research on Cancer (IARC) as possible human carcinogens. Since maize-based foods are significant components of the Mexican diet and there is a high prevalence of genetic susceptibility for folate deficiency among Mexicans, this essay presents international and national evidence of fumonisin exposure and the relevance that such exposure represents for Mexico. PMID- 21031259 TI - Fixations of the HIV-1 env gene refute neutralism: New evidence for pan-selective evolution. AB - We examined 103 nucleotide sequences of the HIV-1 env gene, sampled from 35 countries and tested: I) the random (neutral) distribution of the number of nucleotide changes; II) the proportion of bases at molecular equilibrium; III) the neutral expected homogeneity of the distribution of new fixated bases; IV) the hypothesis of the neighbor influence on the mutation rates in a site. The expected random number of fixations per site was estimated by Bose-Einstein statistics, and the expected frequencies of bases by matrices of mutation fixation rates. The homogeneity of new fixations was analyzed using chi2 and trinomial tests for homogeneity. Fixations of the central base in trinucleotides were used to test the neighbor influence on base substitutions. Neither the number of fixations nor the frequencies of bases fitted the expected neutral distribution. There was a highly significant heterogeneity in the distribution of new fixations, and several sites showed more transversions than transitions, showing that each nucleotide site has its own pattern of change. These three independent results make the neutral theory, the nearly neutral and the neighbor influence hypotheses untenable and indicate that evolution of env is rather highly selective. PMID- 21031260 TI - In vitro antibacterial activity in seed extracts of Manilkara zapota, Anona squamosa, and Tamarindus indica. AB - Extracts prepared from seeds of Manilkara zapota, Anona squamosa, and Tamarindus indica were screened for their antibacterial activity by disc diffusion and broth dilution methods. Acetone and methanol extracts of T. indica seeds were found active against both gram-positive and gram-negative organisms. MIC values of potent extracts against susceptible organisms ranged from 53-380 MUg/mL. Methanol extract of T. indica and acetone extract of M. zapota seeds were found to be bactericidal. PMID- 21031261 TI - Phytochemical and antioxidant studies of Laurera benguelensis growing in Thailand. AB - The aim of this study was to investigate metabolites of the lichen Laurera benguelensis. A high-performance liquid chromatographic (HPLC) method has been developed for the characterization of xanthones and anthraquinones in extracts of this lichen. Lichexanthone, secalonic acid D, norlichexanthon, parietin, emodin, teloschistin and citreorosein were detected in the lichen samples, which were collected from two places in Thailand. Components of the lichen were identified by relative retention time and spectral data. This is the first time that a detailed phytochemical analysis of the lichen L. benguelensis was reported and this paper has chemotaxonomic significance because very little has been published on the secondary metabolites present in Laurera species. Some of the metabolites were detected for the first time in the family Trypetheliaceae. The results of preliminary testing of benzene extract and its chloroform and methanol fractions showed that all samples showed a weak radical scavenging activity. The chloroform extract showed the highest antioxidant activity. PMID- 21031262 TI - In vitro genotoxic effects of four Helichrysum species in human lymphocytes cultures. AB - Helichrysum sanguineum, Helichrysum pamphylicum, Helichrysum orientale, Helichrysum noeanum (Asteraceae) are medicinal plants. For centuries, they have been used as tea in Turkey because of their medicinal properties. So far no scientific evidence has been found in a literature survey regarding the genotoxic effects of these plants. This work evaluated the genotoxic effects on human lymphocyte cultures induced by methanol extracts of these plants, assayed in different concentrations (0.01, 0.05, 0.1, 0.5 and 1 mg/mL). According to the results, Helichrysum noeanum, Helichrysum pamphylicum and Helichrysum sanguineum induced the formation of micronuclei and decreased the mitotic and replication indexes. Helichrysum orientale did not affect these parameters, whereas Helichrysum noeanum, Helichrysum pamphylicum and Helichrysum sanguineum were clearly genotoxic. They should therefore not be used freely in alternative medicine, although their antiproliferative activity may suggest antimitotic and anticarcinogenic properties. Helichrysum orientale could be used in alternative medicine. PMID- 21031263 TI - Effects of heat stress on some blood parameters and egg production of Shika Brown layer chickens transported by road. AB - The effects of vitamins C and E on layer chickens transported by road for 6 h during the hot dry season were investigated. Two experimental groups consisting of thirty Shika Brown layers were separately administered vitamins C and E orally just before transportation, while another 30 layers, which were only given sterile water, served as control. Blood samples analyzed before and after transportation in the control layers showed a decrease (p<0.05) in total white blood cell, (p<0.01) lymphocyte and monocyte values, and a significant (p<0.05) and (p<0.001) increase in the values of eosinophils and heterophils post transportation, respectively. In the experimental groups, post-transportation values of total white blood cells, eosinophils and monocytes were not different (p>0.05) from those obtained before transportation. Heterophil/lymphocyte values were highest in the control group. The result showed that transportation was stressful for the control layers. Post-transportation egg production was not significantly (p>0.05) different in the vitamin E treated group, but values recorded for the vitamin C and control groups were significantly (p<0.05) and (p<0.001) reduced compared to pre-transportation. In conclusion, vitamins C and E administration ameliorated the adverse effect of road transportation stress during the hot dry season. PMID- 21031264 TI - The role of tyrosine 207 in the reaction catalyzed by Saccharomyces cerevisiae phosphoenolpyruvate carboxykinase. AB - The functional significance of tyrosine 207 of Saccharomyces cerevisiae phosphoenolpyruvate carboxykinase was explored by examining the kinetic properties of the Tyr207Leu mutant. The variant enzyme retained the structural characteristics of the wild-type protein as indicated by circular dichroism, intrinsic fluorescence spectroscopy, and gel-exclusion chromatography. Kinetic analyses of the mutated variant showed a 15-fold increase in K(m)CO2, a 32-fold decrease in V(max), and a 6-fold decrease in K(m) for phosphoenolpyruvate. These results suggest that the hydroxyl group of Tyr 207 may polarize CO2 and oxaloacetate, thus facilitating the carboxylation/decarboxylation steps. PMID- 21031265 TI - Lucilia sericata strain from Colombia: Experimental colonization, life tables and evaluation of two artificial diets of the blowfly Lucilia sericata (Meigen) (Diptera: Calliphoridae), Bogota, Colombia strain. AB - The objective of this work was to establish, under experimental laboratory conditions, a colony of Lucilia sericata, Bogota-Colombia strain, to build life tables and evaluate two artificial diets. This blowfly is frequently used in postmortem interval studies and in injury treatment. The parental adult insects collected in Bogota were maintained in cages at 22 degrees C+/-1 average temperature, 60%+/-5 relative humidity and 12 h photoperiodicity. The blowflies were fed on two artificial diets that were evaluated over seven continuous generations. Reproductive and population parameters were assessed. The life cycle of the species was expressed in the number of days of the different stages: egg = 0.8+/-0.1, larvae I = 1.1+/-0.02, larvae II = 1.94+/-0.16, larvae III = 3.5+/ 0.54, pupae = 6.55+/-0.47, male adult = 28.7+/-0.83 and female adult = 33.5+/ 1.0. Total survival from egg stage to adult stage was 91.2% for diet 1, while for diet 2 this parameter was 40.5%. The lifetime reproductive output was 184.51+/ 11.2 eggs per female. The population parameters, as well as the reproductive output of the blowflies that were assessed, showed relatively high values, giving evidence of the continuous increase of the strain over the different generations and making possible its maintenance as a stable colony that has lasted for more than two years. PMID- 21031266 TI - Bone resorptive activity of osteoclast-like cells generated in vitro by PEG induced macrophage fusion. AB - Normal bone remodeling is maintained by a balance between osteoclast and osteoblast activity, whereas defects in osteoclast activity affecting such balance result in metabolic bone disease. Macrophage-macrophage fusion leading to multinucleated osteoclasts being formed is still not well understood. Here we present PEG-induced fusion of macrophages from both U937/A and J774 cell lines and the induced differentiation and activation of osteoclast-like cells according to the expression of osteoclast markers such as tartrate resistant acid phosphatase (TRAP) and bone resorptive activity. PEG-induced macrophage fusion, during the non-confluent stage, significantly increased the osteoclastogenic activity of macrophages from cell lines compared to that of spontaneous cell fusion in the absence of PEG (polyethylene glycol). The results shown in this work provide evidence that cell fusion per se induces osteoclast-like activity. PEG-fused macrophage differential response to pretreatment with osteoclastogenic factors was also examined in terms of its ability to form TRAP positive multinucleated cells (TPMNC) and its resorptive activity on bovine cortical bone slices. Our work has also led to a relatively simple method regarding those previously reported involving cell co-cultures. Multinucleated osteoclast-like cells obtained by PEG-induced fusion of macrophages from cell lines could represent a suitable system for conducting biochemical studies related to basic macrophage fusion mechanisms, bone-resorption activity and the experimental search for bone disease therapeutic alternatives. PMID- 21031267 TI - Ethyl acetate fraction from Cudrania tricuspidata inhibits IL-1beta-induced rheumatoid synovial fibroblast proliferation and MMPs, COX-2 and PGE2 production. AB - OBJECTIVES: The objective of this study is to determine the effects of Ethyl acetate fraction from Cudrania tricuspidata (EACT) on the interleukin-1b (IL-1b) induced proliferation of rheumatoid synovial fibroblasts (RASFs) and production of matrix metalloproteinases (MMPs), cyclooxygenase (COX) and prostaglandin E2 (PGE2) by RASFs. MATERIALS AND METHODS: The proliferation of RASFs was evaluated with CCK-8 reagent in the presence of IL-1b with/without EACT. The expression of MMPs, TIMP-1, COXs, PGE2 and intracellular MAPK signalings, including p-ERK, p p38, p-JNK and NF-kB were examined by immunoblotting or semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and ELISA in conditions as described above. RESULTS: EACT inhibits IL-1beta-induced proliferation of RASFs and MMP-1, 3, COX-2 mRNA and protein expression, PGE2 production induced with IL 1b. EACT also inhibits the phosphorylation of ERK-1/2, p38, JNK and activation of NF-kB by IL-1b. CONCLUSIONS: These results suggest that EACT might be involved in synovial fibroblast proliferation and MMPs, COX-2, and PGE2 production, which are involved in joint destruction in rheumatoid arthritis (RA), indicating that this might be a new therapeutic modality for management of rheumatoid arthritis. PMID- 21031268 TI - Sera of chagasic patients react with antigens from the tomato parasite Phytomonas serpens. AB - The genus Phytomonas comprises trypanosomatids that can parasitize a broad range of plant species. These flagellates can cause diseases in some plant families with a wide geographic distribution, which can result in great economic losses. We have demonstrated previously that Phytomonas serpens 15T, a tomato trypanosomatid, shares antigens with Trypanosoma cruzi, the agent of human Chagas disease. Herein, two-dimensional gel electrophoresis (2-DE) and mass spectrometry (MS) were used to identify proteins of P. serpens 15T that are recognized by sera from patients with Chagas disease. After 2D-electrophoresis of whole-cell lysates, 31 peptides were selected and analyzed by tandem mass spectrometry. Twenty-eight polypeptides were identified, resulting in 22 different putative proteins. The identified proteins were classified into 8 groups according to biological process, most of which were clustered into a cellular metabolic process category. These results generated a collection of proteins that can provide a starting point to obtain insights into antigenic cross reactivity among trypanosomatids and to explore P. serpens antigens as candidates for vaccine and immunologic diagnosis studies. PMID- 21031269 TI - Effect of alternating the magnetic field on phosphate metabolism in the nervous system of Helix pomatia. AB - The effect of extremely low frequency magnetic fields (50 Hz, 0.5 mT) - ELF-MF, on phosphate metabolism has been studied in the isolated ganglions of the garden snail Helix pomatia, after 7 and 16 days of snail exposure to ELF-MF. The influence of ELF-MF on the level of phosphate compounds and intracellular pH was monitored by 31P NMR spectroscopy. Furthermore, the activity of enzymes involved in phosphate turnover, total ATPases, Na+/K+-ATPase and acid phosphatase has been measured. The exposure of snails to the ELF-MF for the period of 7 days shifted intracellular pH toward more alkaline conditions, and increased the activity of investigated enzymes. Prolonged exposure to the ELF-MF for the period of 16 days caused a decrease of PCr and ATP levels and decreased enzyme activity, compared to the 7-day treatment group. Our results can be explained in terms of: 1. increase in phosphate turnover by exposure to the ELF-MF for the period of 7 days, and 2. adaptation of phosphate metabolism in the nervous system of snails to prolonged ELF-MF exposure. PMID- 21031270 TI - Correlations of recognition memory performance with expression and methylation of brain-derived neurotrophic factor in rats. AB - Object recognition memory allows discrimination between novel and familiar objects. This kind of memory consists of two components: recollection, which depends on the hippocampus, and familiarity, which depends on the perirhinal cortex (Pcx). The importance of brain-derived neurotrophic factor (BDNF) for recognition memory has already been recognized. Recent evidence suggests that DNA methylation regulates the expression of BDNF and memory. Behavioral and molecular approaches were used to understand the potential contribution of DNA methylation to recognition memory. To that end, rats were tested for their ability to distinguish novel from familiar objects by using a spontaneous object recognition task. Furthermore, the level of DNA methylation was estimated after trials with a methyl-sensitive PCR. We found a significant correlation between performance on the novel object task and the expression of BDNF, negatively in hippocampal slices and positively in perirhinal cortical slices. By contrast, methylation of DNA in CpG island 1 in the promoter of exon 1 in BDNF only correlated in hippocampal slices, but not in the Pxc cortical slices from trained animals. These results suggest that DNA methylation may be involved in the regulation of the BDNF gene during recognition memory, at least in the hippocampus. PMID- 21031272 TI - The influence of needle size on pain perception in patients treated with botulinum toxin A injections for axillary hyperhidrosis. PMID- 21031273 TI - Solitary, late-onset, self-healing Langerhans cell histiocytosis. PMID- 21031274 TI - Thickening of the skin on the forehead: a quiz. Acanthosis nigricans with forehead location. PMID- 21031275 TI - Secondary intention healing following Mohs micrographic surgery for basal cell carcinoma of the nipple and areola. PMID- 21031276 TI - Desmoplastic spitz naevus can be mistaken for desmoplastic malignant melanoma and dermatofibroma. PMID- 21031277 TI - POEMS syndrome with calciphylaxis: A case report. PMID- 21031278 TI - Genital ulcers associated with Epstein-Barr virus infection (ulcus vulvae acutum). AB - Epstein-Barr virus (EBV) infection may rarely be associated with genital ulcers (ulcus vulvae acutum), a very painful manifestation. The aetiopathogenesis of the disease is not fully understood. We describe here a case of an adolescent virgin with multiple, deep genital ulcers associated with acute infectious mononucleosis. The diagnosis was supported by the clinical symptoms, atypical lymphocytosis, elevated circulating levels of liver enzymes, positive EBV serology, and the detection of EBV in a swab sample and a biopsy specimen by PCR. The virus could not be detected by immunohistochemistry or in situ hybridization. After a short course of methylprednisolone as a supportive treatment, the ulcers healed within one month. No relapse occurred during the 2-year follow-up. Available data relating to the aetiopathogenesis of this condition are reviewed, and we speculate that it may have been caused by percutaneous autoinoculation through cervicovaginal fluid. PMID- 21031279 TI - What can hide under exophytic verrucous appearance? PMID- 21031280 TI - Somatic-type delusional disorder: a case report and comments. PMID- 21031281 TI - No evidence for increased skin cancer risk in Koreans with skin phototypes III-V treated with narrowband UVB phototherapy. AB - Narrowband ultraviolet B (nbUVB) phototherapy is used around the world for the treatment of various skin diseases. However, the carcinogenic risk associated with nbUVB treatment in patients with skin phototypes III-V has not been studied. This retrospective study compared the incidence of skin cancer in Korean patients with skin phototypes III-V treated with nbUVB with that in a control Korean population. A total of 445 nbUVB-treated patients were followed for 1,274 person years (mean follow-up period 34.4 months). No melanoma cases were detected during the follow-up period. How-ever, one patient developed basal cell carcinoma four months after the start of nbUVB phototherapy. For non-melanoma skin cancer, the expected number of cases was 0.059 and the standardized incidence ratio 17.0 (95% confidence interval 0.4-94.8). There were no statistically significant differences between the nbUVB and control groups. Thus, nbUVB phototherapy using TL-01 lamps seems to be a safe therapeutic modality for patients with skin phototypes III-V. PMID- 21031282 TI - Oral and esophageal lichen planus following radiotherapy of nasopharyngeal carcinoma. PMID- 21031283 TI - Paclitaxel-induced neutrophilic adverse reaction and acral erythema. PMID- 21031284 TI - Efficacy of new barrier socks in the treatment of foot allergic contact dermatitis. PMID- 21031285 TI - Comprehensive rehabilitation of patients with rheumatic diseases in a warm climate: a literature review. AB - OBJECTIVE: To present the evidence for the efficacy of comprehensive rehabilitation in a warm climate of patients with a wide variety of rheumatic diseases. METHODS: A systematic review of the literature was undertaken, searching in PubMed, Cinahl, Pedro, SweMed and Embase from 1970 to 2010, and using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation system) criteria. RESULTS: Six studies met the inclusion criteria. For patients with rheumatoid arthritis, moderate evidence was found for reduction of disease activity, pain, fatigue, and global disease impact. The evidence was also moderate that comprehensive rehabilitation in a warm climate did not improve fitness or reduce activity limitation beyond levels reached by rehabilitation in Scandinavia. Among patients with ankylosing spondylitis, low evidence was found for reduction of disease activity, pain, joint range of motion, activity limitation, and global disease impact. In groups with mixed rheumatic diagnoses, low evidence was found for reduction of pain, activity limitation, global disease impact and improved health-related quality of life. No studies on psoriatic arthritis, osteoarthritis, fibromyalgia or osteoporosis were found. CONCLUSION: Well-designed studies to validate and improve the low-to-moderate evidence found for the efficacy of comprehensive rehabilitation in a warm climate among patients with inflammatory rheumatic disease are greatly needed. PMID- 21031286 TI - Circumstances and consequences of falls in polio survivors. AB - OBJECTIVES: Many polio survivors have symptoms that are known risk factors for falls in elderly people. This study aims to determine the: (i) frequency; (ii) consequences; (iii) circumstances; and (iv) factors associated with falls in polio survivors. METHODS: A survey was conducted among 376 polio survivors. Participants completed a falls history questionnaire and additional information was obtained from their medical files. RESULTS: Of the 305 respondents, 74% reported at least one fall in the past year and 60% two or more. Sixteen percent of fallers described a major injury after a fall in the last year and 69% reported fear of falling. One-third of fallers had reduced the amount they walked because of their fear of falling. Most reported falls in a familiar environment (86%), during ambulation (72%) and in the afternoon (50%). Quadriceps weakness of the weakest leg (Medical Research Council (MRC) <= 3), fear of falling and complaints of problems maintaining balance were independently associated with both falls and recurrent falls, while increasing age and medication use were not. CONCLUSION: The high rate of falls and consequences thereof, merit the implementation of fall intervention strategies. To maximize effect, they should be tailor-made and target the fall mechanisms specific to polio survivors. PMID- 21031287 TI - Prevalence of hand symptoms, impairments and activity limitations in rheumatoid arthritis in relation to disease duration. AB - OBJECTIVE: To determine the prevalence of hand and wrist symptoms and impairments, and the resulting activity limitations in relation to disease duration in patients with rheumatoid arthritis. DESIGN AND PATIENTS: A cross sectional study included 200 consecutive patients with rheumatoid arthritis in 4 categories of disease duration: 2-4, 4-6, 6-8 and >= 8 years. Patients were asked about the presence of various hand and wrist symptoms, and underwent a standardized physical examination. To evaluate activity limitations, patients completed the Disabilities of the Arm Shoulder and Hand questionnaire and scored their limitations on a Numerical Rating Scale (0 = no to 10 = maximum limitation). RESULTS: Of all patients, 94% suffered from at least one symptom, and 67% had at least one impairment, mostly from the earliest stages onwards. The median standardized Disabilities of the Arm Shoulder and Hand score (interquartile range) was 26.7 (10.8-42.5). The mean Numerical Rating Scale score for activity limitations was 2.99 (standard deviation 2.50) in the dominant hand and 2.59 (standard deviation 2.49) in the non-dominant hand. CONCLUSION: A high prevalence of hand and wrist symptoms and impairments is often already present after 2 years of disease duration. We recommend that physicians specifically screen for these symptoms and impairments, starting 2 years after the diagnosis of rheumatoid arthritis. PMID- 21031288 TI - Prospective analysis of body mass index during and up to 5 years after discharge from inpatient spinal cord injury rehabilitation. AB - OBJECTIVE: To investigate the prevalence of overweight/obesity and the course of the body mass index (BMI) in persons with spinal cord injury during and after inpatient rehabilitation. DESIGN: Multi-centre longitudinal study. SUBJECTS: A total of 184 persons with spinal cord injury. METHODS: BMI was determined at the start of active rehabilitation, 3 months later, at discharge, and 1, 2 and 5 years after discharge. RESULTS: The percentage of persons who were overweight/obese (BMI >= 22 kg/m2) increased over the years from 56% to 75%. The absolute BMI did not significantly increase during rehabilitation, but showed a significant increase the year after discharge from inpatient rehabilitation (p < 0.001). From examining the personal or lesion characteristics, age was the only factor that was related to the absolute BMI. BMI increased by 1 kg/m2 for each 10 year increase in age. Men, persons with paraplegia and older people had more chance of being overweight/obese compared with women, persons with tetraplegia and younger people. CONCLUSION: The BMI of people with spinal cord injuries gradually increases during and after inpatient rehabilitation, with significant increases in the first year after discharge. It is recommended that emphasis is placed on weight-management protocols (diet and exercise) to encourage a healthy lifestyle. PMID- 21031289 TI - Specific muscle stabilizing as home exercises for persistent pelvic girdle pain after pregnancy: a randomized, controlled clinical trial. AB - OBJECTIVE: To investigate the efficacy of home-based specific stabilizing exercises focusing on the local stabilizing muscles as the only intervention in the treatment of persistent postpartum pelvic girdle pain. DESIGN: A prospective, randomized, single-blinded, clinically controlled study. SUBJECTS: Eighty-eight women with pelvic girdle pain were recruited 3 months after delivery. METHODS: The treatment consisted of specific stabilizing exercises targeting the local trunk muscles. The reference group had a single telephone contact with a physiotherapist. Primary outcome was disability measured with Oswestry Disability Index. Secondary outcomes were pain, health-related quality of life (EQ-5D), symptom satisfaction, and muscle function. RESULTS: No significant differences between groups could be found at 3- or 6-month follow-up regarding primary outcome in disability. Within-group comparisons showed some improvement in both groups in terms of disability, pain, symptom satisfaction and muscle function compared with baseline, although the majority still experienced pelvic girdle pain. CONCLUSION: Treatment with this home-training concept of specific stabilizing exercises targeting the local muscles was no more effective in improving consequences of persistent postpartum pelvic girdle pain than the clinically natural course. Regardless of whether treatment with specific stabilizing exercises was carried out, the majority of women still experienced some back pain almost one year after pregnancy. PMID- 21031290 TI - Psychometric evaluation of the Northwick Park Dependency Scale. AB - OBJECTIVE: To examine the psychometric properties of the Northwick Park Dependency Scale (NPDS). DESIGN: Review of existing literature and psychometric analysis in relation to other standardized measures of disability in a large neurorehabilitation cohort. SETTING: A regional post-acute specialist inpatient neurorehabilitation unit in London, UK. PARTICIPANTS: A total of 569 inpatients with complex neurological disabilities (350 males, 219 females; mean age 44.4 years). MAIN MEASURES: The NPDS, Barthel Index, Functional Independence and Functional Assessment measures. RESULTS: A database search found 5 studies that examined the psychometrics of the NPDS. These supported its validity and reliability. The present study added to these by evaluating the internal consistency, factor structure, discriminatory power and responsiveness to change during rehabilitation. The NPDS was found to have good internal consistency (alpha = 0.90), suggesting that it can reasonably be summed to a single total score. It discriminated among people with different levels of dependency and was responsive to change, particularly in the higher dependency groups. CONCLUSION: The NPDS is a psychometrically robust tool, providing a broader range of information on nursing needs than some other commonly-used disability measures. The Special Nursing Needs subscale provides clinically useful information, but its metric properties require further development, which is now underway. PMID- 21031291 TI - Changes in satisfaction with activities and participitation between acute, post acute and chronic stroke phases: a responsiveness study of the SATIS-Stroke questionnaire. AB - OBJECTIVE: To investigate clinical changes among the acute, post-acute and chronic phases in stroke patients' satisfaction with activities and participation. The SATIS-Stroke questionnaire's sensitivity to change was investigated with a sample of 45 stroke patients. METHODS: The SATIS-Stroke questionnaire was used to collect data from the 45 patients (mean age 69 years, 64% men) in the acute, post-acute and chronic stroke phases. Responsiveness of the questionnaire was investigated using a sample approach (effect size and standardized response mean indices) and an individual approach (t statistic). The clinical significance of change was also calculated using the empirical rule of effect size and the minimal clinically important difference. RESULTS: Analysis of variance showed a significant difference among evaluations in the 3 phases (F = 13.662; 2 df; p < 0.001). Post-hoc analysis showed a significant change between the acute and post-acute phases, but no significant change between the post-acute and chronic phases. Effect size and standardized response mean indices showed that the greatest change in satisfaction with activity and participation was between the acute and the chronic phases. Analysis of the clinical significance of change indicated that greater changes in satisfaction were necessary to detect clinically relevant improvement over time than clinically relevant deterioration. CONCLUSION: The SATIS-Stroke questionnaire successfully determined changes in satisfaction among stroke patients. PMID- 21031292 TI - Economic evaluation of a geriatric rehabilitation programme: a randomized controlled trial. AB - OBJECTIVE: Cost-effectiveness of a geriatric rehabilitation programme. DESIGN: Economic evaluation alongside a randomized controlled trial. METHODS: A total of 741 subjects with progressively decreasing functional ability and unspecific morbidity were randomly assigned to either an inpatient rehabilitation programme (intervention group) or standard care (control group). The difference between the mean cost per person for 12 months' care in the rehabilitation and control groups (incremental cost) and the ratio between incremental cost and effectiveness were calculated. Clinical outcomes were functional ability (Functional Independence Measure (FIM(TM))) and health-related quality of life (15D score). RESULTS: The FIM(TM) score decreased by 3.41 (standard deviation 6.7) points in intervention group and 4.35 (standard deviation 8.0) in control group (p = 0.0987). The decrease in the 15D was equal in both groups. The mean incremental cost of adding rehabilitation to standard care was 3111 euros per person. The incremental cost effectiveness ratio for FIMTM did not show any clinically significant change, and the rehabilitation was more costly than standard care. A cost-effectiveness acceptability curve suggests that if decision-makers were willing to pay 4000 euros for a 1-point improvement in FIMTM, the rehabilitation would be cost effective with 70% certainty. CONCLUSION: The rehabilitation programme was not cost-effective compared with standard care, and further development of outpatient protocols may be advisable. PMID- 21031293 TI - Validity and reliability of the de Morton Mobility Index in the subacute hospital setting in a geriatric evaluation and management population. AB - OBJECTIVE: To investigate the clinimetric properties of the de Morton Mobility Index (DEMMI) in a Geriatric Evaluation and Management (GEM) population. DESIGN: A longitudinal validation study (n = 100) and inter-rater reliability study (n = 29) in a GEM population. PATIENTS: Consecutive patients admitted to a GEM rehabilitation ward were eligible for inclusion. METHODS: At hospital admission and discharge, a physical therapist assessed patients with physical performance instruments that included the 6-metre walk test, step test, Clinical Test of Sensory Organization and Balance, Timed Up and Go test, 6-minute walk test and the DEMMI. Consecutively eligible patients were included in an inter-rater reliability study between physical therapists. RESULTS: DEMMI admission scores were normally distributed (mean 30.2, standard deviation 16.7) and other activity limitation instruments had either a floor or a ceiling effect. Evidence of convergent, discriminant and known groups validity for the DEMMI were obtained. The minimal detectable change with 90% confidence was 10.5 (95% confidence interval 6.1-17.9) points and the minimally clinically important difference was 8.4 points on the 100-point interval DEMMI scale. CONCLUSION: The DEMMI provides clinicians with an accurate and valid method of measuring mobility for geriatric patients in the subacute hospital setting. PMID- 21031294 TI - Correlation of motor function with transcallosal and intracortical inhibition after stroke. AB - OBJECTIVE: The inhibitory role of neuronal networks in motor recovery after stroke remains to be elucidated. We examined the influence of transcallosal inhibition and short intracortical inhibition on motor recovery after stroke. We also investigated the correlation between transcallosal inhibition and mirror activity. DESIGN: A cross-sectional study. SUBJECTS: Thirty-eight chronic stroke patients. METHODS: Transcallosal inhibition was evaluated using single transcranial magnetic stimulation, and short intracortical inhibition was assessed using paired-pulse transcranial magnetic stimulation. Mirror activity was measured during tonic contraction of the contralateral hand. RESULTS: Transcallosal inhibition from the contralesional to the ipsilesional motor cortex correlated positively with motor function of the paretic hand; in contrast, transcallosal inhibition to the ipsilesional motor cortex correlated negatively with mirror activity of the paretic hand in both cortical and subcortical stroke patients. Short intracortical inhibition of the ipsilesional motor cortex correlated negatively with motor function of the paretic hand in only the subcortical stroke patients. CONCLUSION: Transcallosal inhibition from the contralesional to the ipsilesional motor cortex may inhibit mirror movements in stroke patients with good motor function. The weak transcallosal inhibition in patients after stroke with poor motor function may be ineffective for inhibiting mirror movement; however, it may have the advantage of facilitating motor recovery. PMID- 21031295 TI - Heterogeneous assessment of shoulder disorders: validation of the Standardized Index of Shoulder Function. AB - OBJECTIVE: Although 40 assessment tools are described in the literature, very few of them have been correctly validated. The Standardized Index of Shoulder Function (FI2S) encompasses pain, mobility, strength and function. The aim of this work is to describe the FI2S and to study its construct validity, reliability and responsiveness to change. PATIENTS: Fifty-nine patients with non surgical (rotator cuff lesions, frozen shoulders, osteoarthritis) or post surgical (acromioplasty, repairs of rotator cuff tears, arthroplasty) shoulder disorders were included. METHODS: The FI2S was compared with the Disabilities of the Arm, Shoulder and Hand questionnaire (DASH), with the Constant-Murley Score (CMS), and with a visual analogue scale for pain. RESULTS: Inter-test reliability and inter-rater reliability are excellent, with intra-class correlation coefficient of 0.93 (0.88-0.96) and 0.94 (0.90-0.96), respectively. Under a convergent hypothesis, the Spearman's correlation coefficients with the CMS and DASH score are 0.91 (p < 0.0001) and -0.64 (p < 0.0001), respectively. Correlations between the FI2S and the CMS are excellent for mobility and strength, but moderate for pain and functional capacities. Under a divergent hypothesis, no correlation is observed between the FI2S total score and age. Responsiveness to change is excellent. CONCLUSION: The FI2S appears to be a proper assessment tool for pain, mobility, strength and function in shoulder disorders, easy to administer and of good metric value. PMID- 21031296 TI - Effect of repetitive transcranial magnetic stimulation in a patient with chronic crossed aphasia: fMRI study. AB - OBJECTIVE: We report here the case of a 52-year-old Korean woman who was initially diagnosed with non-fluent/global crossed aphasia. METHODS AND RESULTS: Initial computed tomography of the brain revealed a haematoma of approximately 40 ml in the right basal ganglia area and cavitation around the right lateral ventricle. Three years after onset the aphasia was resolved to a conduction aphasia and she had an ongoing left-sided gait disturbance. Follow-up anatomical magnetic resonance imaging found no recurrence of haemorrhage. Language functional magnetic resonance imaging was examined before and after repetitive transcranial magnetic stimulation treatment. A 90-mm round coil stimulator was used and the repetitive transcranial magnetic stimulation treatment location was P3 on the 10-20 International electrode placement system (1 Hz, 20 min per day for 10 days over a 2-week period). Functional magnetic resonance imaging results before repetitive transcranial magnetic stimulation treatment showed no significant activity in either the ipsilesional or contralesional hemispheres for noun generation and sentence completion paradigms (p < 0.001, cluster size 128). Compared with the pre-treatment phase, following repetitive transcranial magnetic stimulation treatment the data from functional magnetic resonance imaging revealed significant activations in the right inferior frontal lobe (Broca's area), posterior temporal gyrus (Wernicke's area), and parietal lobe for both the noun generation and sentence completion tasks (p < 0.001, cluster size 128). CONCLUSION: This functional magnetic resonance imaging case study is the first to suggest the use of repetitive transcranial magnetic stimulation for improving language outcome in a patient with crossed aphasia. In addition, we report the value of language functional magnetic resonance imaging before and after repetitive transcranial magnetic stimulation treatment for determining the effect of treatment and the underlying neurobiological mechanism of functional recovery following repetitive transcranial magnetic stimulation treatment. PMID- 21031297 TI - Degeneration of cingulum and fornix in a patient with traumatic brain injury: diffuse tensor tractography study. AB - OBJECTIVES: The cingulum and fornix are important structures for memory function. Using follow-up diffusion tensor tractography in a patient with traumatic brain injury we found degeneration of the cingulum and fornix. CASE REPORT: An 18-year old male who had had a traffic accident underwent conservative management for diffuse axonal injury. Brain magnetic resonance imaging showed an encephalomalactic lesion in the posterior portion of the corpus callosum. The patient had severe cognitive problems at 3 months after onset. However, while his intelligence had improved, his memory impairment had been aggravated at 14 months from onset. RESULTS: On the first diffusion tensor tractographies, the integrity of both corticospinal tracts, right cingulum, and left fornix were preserved; however, compared with controls, there were disruptions in both ends of the left cingulum and right fornical crus. On the second diffusion tensor tractographies, both the cingulum and fornix showed severe degeneration, although the integrities of both corticospinal tracts were well preserved. CONCLUSION: We conclude that patients with memory impairment following traumatic brain injury should be evaluated using diffusion tensor imaging. In addition, follow-up diffusion tensor imaging may be necessary in patients with sustained memory impairment. PMID- 21031300 TI - Bioassays of quorum sensing compounds using Agrobacterium tumefaciens and Chromobacterium violaceum. AB - In most bacteria, a global level of regulation exists involving intercellular communication via the production and response to cell density-dependent signal molecules. This cell density-dependent regulation has been termed quorum sensing (QS). QS is a global regulator, which has been associated with a number of important features in bacteria including virulence regulation and biofilm formation. Consequently, there is considerable interest in understanding, detecting, and inhibiting QS. Acyl homoserine lactones (acyl HSLs) are used as extracellular QS signals by a variety of Gram-negative bacteria. Chromobacterium violaceum, a Gram-negative bacterium commonly found in soil and water, produces the characteristic purple pigment violacein, the production of which is regulated by acyl HSL-mediated QS. Based on this readily observed pigmentation phenotype, C. violaceum strains can be used to detect various aspects of acyl HSL-mediated QS activity. In another commonly used bioassay organism, Agrobacterium tumefaciens, QS can be detected by the use of a reporter gene such as lacZ. Here, we describe several commonly used approaches incorporating C. violaceum and A. tumefaciens that can be used to detect acyl HSLs and QS inhibition. PMID- 21031301 TI - Detection of 2-alkyl-4-quinolones using biosensors. AB - 2-alkyl-4-quinolones (AQs) such as 2-heptyl-3-hydroxy-4-quinolone (PQS) and 2 heptyl-4-quinolone (HHQ) are quorum sensing signal molecules. Here we describe two methods for AQ detection and quantification that employ thin layer chromatography (TLC) and microtitre plate assays in combination with a lux-based Pseudomonas aeruginosa AQ biosensor strain. For TLC detection, organic solvent extracts of bacterial cells or spent culture supernatants are chromatographed on TLC plates, which are then dried and overlaid with the AQ biosensor. After detection by the bioreporter, AQs appear as both luminescent and green (pyocyanin) spots. For the microtitre assay, either spent bacterial culture supernatants or extracts are added to a growth medium containing the AQ biosensor. Light output by the bioreporter is proportional to the AQ content of the sample. The assays described are simple to perform, do not require sophisticated instrumentation, and are highly amenable to screening large numbers of bacterial samples. PMID- 21031302 TI - FRET-based biosensors for the detection and quantification of AI-2 class of quorum sensing compounds. AB - Intercellular small molecular weight signaling molecules modulate a variety of biological functions in bacteria. One of the more complex behaviors mediated by intercellular signaling molecules is the suite of activities regulated by quorum sensing molecules. These molecules mediate a variety of population-dependent responses, including the expression of genes that regulate bioluminescence, type III secretion, siderophore production, colony morphology, biofilm formation, and metalloprotease production. Given their central role in regulating these responses, the detection and quantification of QS molecules has important practical implications. Until recently, the detection of QS molecules from Gram negative bacteria has relied primarily on bacterial reporter systems. These bioassays though immensely useful are subject to interference by compounds that affect bacterial growth and metabolism. In addition, the reporter response is highly dependent on culture age and cell population density. To overcome such limitations, we developed an in vitro protein-based assay system for the rapid detection and quantification of the furanosyl borate diester (BAI-2) subclass of autoinducer-2 (AI-2) QS molecules. The biosensor is based on the interaction of BAI-2 with the Vibrio harveyi QS receptor LuxP. Conformation changes associated with BAI-2 binding to the LuxP receptor change the orientation of cyan and yellow variants of GFP (CFP and YFP) fused the N- and C-termini, respectively, of the LuxP receptor. LuxP-BAI2 binding induces changes in fluorescence resonance energy transfer (FRET) between CFP and YFP, whose magnitude of change is ligand concentration dependent. A set of ligand-insensitive LuxP-mutant FRET protein sensor was also developed for use as control biosensors. The FRET-based BAI-2 biosensor responds selectively to both synthetic and biologically derived BAI 2compounds. This report describes the use of the LuxP-FRET biosensor for the detection and quantification of BAI-2. PMID- 21031303 TI - Isolation of agr quorum sensing autoinducers. AB - Autoregulation of genes is often associated with quorum sensing systems where bacteria produce and secrete molecules that allow the cells to communicate with one another, leading to the activation of certain genes at certain population densities. Here we describe the identification of the agr as a quorum sensing system in Staphylococcus aureus and the isolation of agr autoinducers and inhibitors by northern blotting, real-time RT-PCR, and beta-lactamase reporter cells assays. PMID- 21031304 TI - Liquid chromatography/mass spectrometry for the detection and quantification of N acyl-L-homoserine lactones and 4-hydroxy-2-alkylquinolines. AB - High-performance liquid chromatography (HPLC) coupled in-line with mass spectrometry (MS) permits rapid and specific identification and quantification of N-acyl-L-homoserine lactones (AHLs) and 4-hydroxy-2-alkylquinolines (HAQs). We are presenting here methods for the analysis of these molecules directly from biological samples using LC/MS. PMID- 21031305 TI - Detection of autoinducer (AI-2)-like activity in food samples. AB - The contamination, survival, and possible foodborne disease outbreaks are major issues confronting the food industry. However, from a microbial perspective, any food whether natural or processed is just another environmental niche that is available for colonization. Quorum sensing or cell-cell communication is a process by which microorganisms are thought to communicate with each other using a variety of small molecules termed autoinducers. The autoinducer AI-2 is thought to be a universal signaling molecule due to its ability to modulate the gene expression of a number of different bacterial species and genera. Pathogens such as Pseudomonas aeruginosa, Aeromonas hydrophila, Vibrio anguillarum, Streptococcus sp., and Burkholderia cepacia form biofilms on a variety of man made and natural surfaces using cell-cell mechanisms. It is important to detect and study autoinducers and their activities in foods, since a better understanding of these molecules in food and food ingredients may help in designing new approaches to thwart microbial persistence and biofilm formation. The autoinducer AI-2 is thought to be involved in microbial attachment and biofilm formation leading to food spoilage. To better understand microbial cell cell signaling in foods especially as it relates to pathogen persistence, biofilm formation, and food spoilage, methods to process, extract, and purify autoinducer molecules need to be developed. This chapter details methods to process food samples to obtain cell-free supernatants (CFS), which could subsequently be tested for the presence of AI-2 or "AI-2-like activity" in the extracted CFS using autoinducer bioassays. Additionally, the method of synthesizing AI-2 in the laboratory is also provided. The methods that are presented in this chapter are based on previously published research articles from the authors' laboratory. PMID- 21031306 TI - Detection of bacterial signaling molecules in liquid or gaseous environments. AB - The detection of bacterial signaling molecules in liquid or gaseous environments has been occurring in nature for billions of years. More recently, man-made materials and systems has also allowed for the detection of small molecules in liquid or gaseous environments. This chapter will outline some examples of these man-made detection systems by detailing several acoustic-wave sensor systems applicable to quorum sensing. More importantly though, a comparison will be made between existing bacterial quorum sensing signaling systems, such as the Vibrio harveyi two-component system and that of man-made detection systems, such as acoustic-wave sensor systems and digital communication receivers similar to those used in simple cell phone technology. It will be demonstrated that the system block diagrams for either bacterial quorum sensing systems or man-made detection systems are all very similar, and that the established modeling techniques for digital communications and acoustic-wave sensors can also be transformed to quorum sensing systems. PMID- 21031307 TI - Determination of acyl homoserine lactone and tetramic acid concentrations in biological samples. AB - Within environmental communities, there is a constant struggle for survival, as nutrients are often limited. In response, bacteria have developed elaborate methods to deal with competitors. One such mechanism is the coordination of behaviors and function via the exchange of small chemical signals in a process known as quorum sensing. This process is especially prominent in the pathogenicity of Pseudomonas aeruginosa, an opportunistic human pathogen that forms sessile communities known as biofilms. These biofilms play an important role in the lifestyle of P. aeruginosa, either in their natural environment or during establishment and maintenance of infection in human hosts; thus, they often have grievous effects on human health. As such, a method for the detection of these QS signals may provide insights into the pathogenicity and survival of P. aeruginosa. In this chapter, we present a method for the extraction and quantitation of the P. aeruginosa QS signal N-3-oxo-dodecanoyl-homoserine lactone, and its rearranged tetramic acid product, C12-TA, which itself has implications as a survival tactic used by P. aeruginosa. PMID- 21031308 TI - Luminescent reporters and their applications for the characterization of signals and signal-mimics that alter LasR-mediated quorum sensing. AB - In many pathogenic bacteria, quorum sensing (QS) controls expression of genes that are involved in virulence, production and resistance to antibiotics, formation and maintenance of microbial multicellular consortia on biotic and abiotic surfaces of medical and industrial importance. N-acyl homoserine lactones (AHL) are the best characterized quorum sensing signals in Gram-negative bacteria. Interference with AHL-mediated QS, therefore, is considered an attractive strategy for controlling virulence in pathogens. The search for AHL signals and their mimics has been facilitated by the development of sensitive bioassays, in which QS reporters luminesce in response to AHL signals. These bioassays have already led to the identification of dozens of compounds with QS modulating activities. The characterization of the mode of action of QS signals and their mimics requires follow-up biochemical studies. Here, we describe a set of luminescent reporters, which could be used in high, medium or low throughput format, for the discovery and validation of agonists or antagonists of the Las QS system of Pseudomonas aeruginosa. These nearly isogenic reporters contain truncations or point mutations in the AHL binding domain of the AHL receptor LasR, as well as mutations in the promoter for the gene encoding LasI AHL synthase. We also developed reporters for documenting the regulation of lasI and lasR promoters. The use of these reporters significantly streamlines identification and characterization of the Las QS signal agonists and antagonists prior to biochemical experiments. To test the usefulness of these reporters, we carried out bioassays with patulin, a known inhibitor of Las QS. PMID- 21031309 TI - Modulation of mammalian cell processes by bacterial quorum sensing molecules. AB - Microbial pathogens use a wide repertoire of pathogen-associated molecular patterns (PAMPs) that affect host cell responses through activation of intracellular signaling events in a PAMP-specific manner. Here we describe a set of western blot-based methodologies for the evaluation of biochemical effects specifically induced by N-(3-oxo-acyl) homoserine lactones (3-oxo-AHLs) small molecules secreted by a number of Gram-negative bacteria, including the opportunistic human pathogen Pseudomonas aeruginosa. First, we will highlight the AHL-mediated effects on proapoptotic and stress pathways. Secondly, we will demonstrate that AHLs possess the ability to alter stimulus-induced NF-kappaB signaling, a key biochemical marker of inflammation and innate immune responses. PMID- 21031310 TI - Imaging N-acyl homoserine lactone quorum sensing in vivo. AB - In order to study N-acyl homoserine lactone (AHL)-based quorum sensing in vivo, we present a protocol using an Escherichia coli strain equipped with a luxR-based monitor system, which in the presence of exogenous AHL molecules expresses a green fluorescent protein (GFP). Lungs from mice challenged intratracheally with alginate beads containing both a P. aeruginosa strain together with the E. coli monitor strain can be investigated at different time points postinfection. Epifluorescent or confocal scanning laser microscopy (CSLM) is used to detect the GFP-expressing E. coli monitor strain in the lung tissues, indicating production and excretion of AHLs in vivo by the infecting P. aeruginosa. PMID- 21031311 TI - Defining the structure and function of acyl-homoserine lactone autoinducers. AB - Quorum sensing plays a central role in regulating many community-derived symbiotic and pathogenic relationships of bacteria, and as such has attracted much attention in recent years. Acyl-homoserine lactones (AHLs) are important signaling molecules in the quorum sensing gene-regulatory processes found in numerous gram-negative species of bacteria that interact with eukaryotic organisms. AHLs are produced by acyl-homoserine lactone synthases. Bacteria can have multiple genes for AHL synthase enzymes, and such species are likely to produce several different types of AHLs. Determination of the types and the relative amounts of AHLs produced by AHL synthases in bacteria under varied conditions provides important insights into the mechanism of AHL synthase function and the regulation of transcriptional cascades initiated by quorum sensing signaling. This chapter describes a mass spectrometry method for determining the types and relative amounts of AHLs present in a sample. PMID- 21031312 TI - Global expression analysis of quorum-sensing controlled genes. AB - Transcript profiling has improved our understanding of quorum-sensing gene regulation on a global scale. Here, we describe methods for high-quality sample preparation for use in DNA microarray and real-time PCR experiments. PMID- 21031313 TI - Small RNA target genes and regulatory connections in the Vibrio cholerae quorum sensing system. AB - The two-component quorum sensing (QS) system, first described in the marine bacterium Vibrio harveyi and evolutionarily conserved among members of the genus Vibrio, has been best studied in the human pathogen Vibrio cholerae (1, 2). In the V. cholerae QS system, the response to the accumulation of extracellular autoinducers triggers a signaling cascade resulting in the transcription of four small regulatory RNAs (sRNAs). Our results support the model that the QS sRNAs bind to the 5' untranslated region of multiple mRNAs and alter the fate of one in a positive manner and several others in a negative manner. This mechanism ensures the proper timing of the QS response, which includes the expression of traits critical for virulence and for the formation of biofilms (2-6). PMID- 21031315 TI - Linking quorum sensing regulation and biofilm formation by Candida albicans. AB - Candida albicans biofilms are surface-associated, structured communities composed of yeast, hyphal, and pseudohyphal cells surrounded by an extracellular matrix. C. albicans biofilms often lead to life-threatening systemic infections and are particularly difficult to eradicate because of their high levels of resistance to antibiotics. Farnesol, an autoregulatory molecule secreted by C. albicans, inhibits hyphal growth and the expression of a number of morphology-specific genes that are necessary for robust biofilm formation. Many stages of biofilm development are impacted by farnesol including the adherence of cells to the substratum, the architecture of mature biofilms, and the dispersal of cells from biofilms. For these reasons, understanding the mechanisms of action of farnesol could lead to the development of new antifungal compounds that target C. albicans biofilm cells, perhaps rendering biofilms more sensitive to antibiotics. Here, we describe several methods for the analysis of the effects of farnesol on biofilm formation and function. PMID- 21031314 TI - Quantifying Pseudomonas aeruginosa quinolones and examining their interactions with lipids. AB - Pseudomonas aeruginosa produces a quorum sensing molecule termed the Pseudomonas Quinolone Signal (2-heptyl-3-hydroxy-4-quinolone; PQS) that regulates an array of genes involved in virulence. This chapter addresses four related techniques useful for detecting and quantifying PQS. First, extraction of PQS from complex mixtures (e.g. cell cultures) is described. Separation of PQS from extracts by Thin-Layer Chromatography (TLC) is used in combination with the natural fluorescence of the molecule for quantification. A second separation technique for the PQS precursor HHQ using High-Performance Liquid Chromatography (HPLC) is also described, and this assay exploits the molecule's characteristic absorbance for quantification. A third method for quantification of PQS from simple mixtures (e.g. enzyme assays) using fluorescence is outlined. Finally, a protocol for determining PQS interactions with membrane lipids through Fluorescence Resonance Energy Transfer (FRET) is presented. These techniques allow for quantification and characterization of PQS from diverse environments, a prerequisite to understanding the biological functions of QS molecules. PMID- 21031316 TI - Design of synthetic mammalian quorum-sensing systems. AB - Synthetic quorum-sensing systems in mammalian cells has enabled the implementation of time- and distance-dependent bioprocesses, as well as the design of synthetic ecosystems emulating clinically important host-parasite interactions. In this chapter, we provide a detailed protocol of the design of a mammalian cell-to-cell signaling device and its integration into a mammalian quorum-sensing system for cell density-induced expression product genes. Cell-to cell signaling is based on a sender cell, metabolically engineered for expression of alcohol dehydrogenase converting ethanol into acetaldehyde, and a receiver cell line for the dose-dependent translation of the acetaldehyde concentration into transgene expression by an acetaldehyde-responsive promoter. This protocol can be adapted easily to various cell types and transgenes for the design of versatile mammalian cell-based quorum-sensing systems. PMID- 21031317 TI - Qualitative and quantitative determination of quorum sensing inhibition in vitro. AB - The formation of biofilms in conjunction with quorum sensing (QS)-regulated expression of virulence by opportunistic pathogens contributes significantly to immune evasion and tolerance to a variety of antimicrobial treatments. The present protocol describes methods to determine the in vitro efficacy of potential quorum sensing inhibitors (QSIs). Work on Pseudomonas aeruginosa has shown that chemical blockage of QS is a promising new antimicrobial strategy. Several live bacterial reporter systems been developed to screen extracts and pure compounds for QSI activity. Here we describe the usage of reporter strains consisting of a lasB-gfp or rhlA-gfp fusion in P. aeruginosa for qualitative and quantitative evaluation of the inhibition of the two major QS pathways, monitored as reduced expression of green fluorescence. By the use of an in vitro flow cell system it is possible to study the QSI activity by monitoring its ability to interfere with the protective functions of bacterial biofilm. For evaluation of the global effects of QSI compounds, we present a protocol for the DNA microarray based transcriptomics. Using these in vitro methods it is possible to evaluate the potential of various QSI compounds. PMID- 21031318 TI - Custom synthesis of autoinducers and their analogues. AB - Bacterial quorum sensing (QS) system is a unique target for the development of a new class of drugs that potentially control pathogenicity and attenuate virulence. Thus, it has been of significant interest to discover small organic molecules that modulate QS circuits by competing with the signaling molecules, or so-called autoinducers (AIs), for binding to QS proteins. In this chapter, we summarize synthetic methodology for custom QS agonists and antagonists against the Lux system in Gram-negative bacteria. PMID- 21031319 TI - Heterologous overexpression, purification, and in vitro characterization of AHL lactonases. AB - Quorum-quenching enzymes are useful as biochemical tools and possible therapeutic proteins. One of the best-characterized families of these catalysts is the N-acyl L-homoserine lactone (AHL) lactonases, which rely on a dinuclear metal ion active site to hydrolytically cleave the autoinducer's lactone bond and inactivate signaling. A detailed understanding of how this enzyme works can help in the design of more selective and efficient reagents. To facilitate these studies, we describe a methodology to heterologously express, purify, and conduct in vitro characterization of several metalloforms of the AHL lactonase from Bacillus thuringiensis (AiiA). These procedures should be applicable to similar enzymes and will facilitate the production of more useful quorum-quenching reagents for biochemical studies and possible therapeutic applications. PMID- 21031320 TI - High-performance liquid chromatography analysis of N-acyl homoserine lactone hydrolysis by paraoxonases. AB - Mammalian paraoxonases (PONs) are a unique, highly conserved family of calcium dependent esterases consisting of PON1, PON2, and PON3. The PONs can hydrolyze the lactone ring of a range of N-acyl-L: -homoserine lactone (AHL) quorum sensing signaling molecules, rendering them inactive. This chapter describes a method that utilizes high-performance liquid chromatography analysis with UV detection for determining the rate of AHL hydrolysis in cell lysates, tissue homogenates, serum, and with purified proteins. Also described are the techniques used to prepare cell culture lysates and tissue homogenates for analysis and the use of class-specific enzyme inhibitors to determine the contribution of PONs to AHL hydrolysis in the samples. PMID- 21031322 TI - [Multimodal imaging in medullary thyroid carcinomas]. PMID- 21031323 TI - [An introduction to the cardiac and vascular diagnostics team]. PMID- 21031321 TI - Generation of quorum quenching antibodies. AB - The exchange of information within and among bacterial populations using small diffusible molecules has been termed "quorum sensing" (QS). Due to the extracellular distribution of the QS autoinducer molecules and the evolutionary highly conserved nature of signaling components, microbial QS systems represent an excellent target for anti-infective immunotherapy. Recently, we have described the generation of quorum quenching monoclonal antibodies (mAbs) against acyl homoserine lactones (AHL) used by Pseudomonas aeruginosa as well as Staphylococcal autoinducing peptides (AIP). These mAbs suppressed QS signaling in bacteria and neutralized AHL-mediated cytotoxic effects in vitro, as well as protected animals in Staphylococcus aureus infection models. PMID- 21031325 TI - [Refinancing obstetrics]. PMID- 21031324 TI - [Comment by the AGO Uterus Committee on the consensus publication of the 3rd Radiologic-Gynecologic Expert Assembly on the treatment of uterine leiomyoma by uterine artery embolization in Munich 15 January 2010]. PMID- 21031326 TI - ["Save today, better control tomorrow"]. PMID- 21031327 TI - [Economic perspectives of health care]. AB - International comparisons show that life expectancy is positively correlated with national expenditures on health care (% of Gross National Product) - albeit with significant differences. Over the past decade the increase in health-care expenditures grew at twice the rate of the increase in life expectancy. Total volume and growth of resources spent on health care require more consideration of economic aspects. On the basis of empirical examples (World Health Organization) and diagrammatic illustrations of the efficiency of market mechanisms, the present paper offers a visual illustration of the argument that market-oriented health systems seem to be more effective, and that government rules and regulations have to consider the demand AND supply sides of health care as well freedom AND responsibility simultaneously. PMID- 21031328 TI - [Costs and revenues for a birth in Germany]. AB - INTRODUCTION Based on the data of the Institut fur das Entgeltsystem im Krankenhaus (InEK) cost and revenue data for deliveries in Germany can be compared. The InEK calculates the cost data for each individual diagnosis-related group (DRG) on the basis of those hospitals that deliver their individual cost data, so-called "Kalkulationshauser". The InEK only publishes data for patients with standard lengths of stay. It does not deliver data for short- and long-stay patients. Beside these cost data, the InEK publishes the nationwide case volume for each DRG. Having a knowledge of the individual base rate (Landesbasisfallwert), which differs from province (Bundesland) to province and, in addition, the nationwide case weight for each DRG, the average revenues for deliveries in general, vaginal deliveries, and Cesarean sections can be calculated. These revenue data differ not only from province to province, but from hospital to hospital because of the individual hospital-specific base rates. MATERIALS AND METHODS: The average costs for a delivery in general, a vaginal delivery, and a Cesarean section were calculated on the basis of the DRG Report Browsers 2005/2007-2007/2009 published by the InEK. The costs for short- and long stay patients were estimated on the basis of a scenario technique. The revenues were calculated on the basis of the published DRG catalogues, which supply individual case weights, and the county-wide base rate. Short- and long-stay revenues again had to be estimated by a scenario technique. In every DRG the cost data create the basis for the case weight two years later. RESULTS: In relation to the average base rate over all provinces the 2005 costs are higher than the revenues in each province. Even in Rhineland-Palatinate, the county with the highest base rate, costs and revenues are at par. Only the declining costs from 2005-2007 balance the costs and revenues nationwide. But in provinces with low base rates the revenues stay lower than costs. These data demonstrate the pressure of rationalisation on German perinatal medicine and their hospitals. Cost and revenue comparisons with other countries are of lesser interest. Most countries have totally different systems for financing hospitals. In Germany, the published data show only the running costs financed by public and private health care insurances. Infrastructure costs are financed by the government. In other countries not only the running costs but also the investment costs must be financed by running revenues too. PMID- 21031329 TI - [Structure and reimbursement in obstetrics - are births in level I perinatal centres economically sound?]. AB - INTRODUCTION: The standardization of the profit in the public health system causes the question if obstetrical departments of different structures can work cost-coveringly and which services in the DRG-system operate in deficit or profitably. This problem mainly refers to the hospitals of obstetrical maximal care, namely the perinatal centre of level I. MATERIAL AND METHODS: Based on the body cost accounting according to InEK-Matrix the average actual costs of an obstetrical department level IV, a perinatal centre level I and university hospitals were found out for the obstetrical DRGs and compared with the profits calculated by InEK. An analysis of the costs was carried out concerning the cost relevance for different cost areas. RESULTS: Spontaneous delivery was the service that turned out to be cost-covering in all structures. The real costs of caesarean sections, however, as well as those of some vaginal kinds of delivery, mainly pre-mature births and complicated diagnoses turned out to be not cost covering. However, the perinatal centre was able to compensate the deficit by the high number of vaginal deliveries. The actual personel costs for physicians were higher in the perinatal center than the InEK-calculation for all obstetrical DRGs. The costs of nursery and the costs of the non-medical infrastructure were partly smaller than those of the InEK-calculation. CONCLUSION: A perinatal center level I can operate cost-coveringly on the basis of the DRG system. To achieve this it's not necessary to increase the number of caesarean sections, but what is needed instead is a high number of normal deliveries and an economical non medical infrastructure and care. PMID- 21031330 TI - [Management of dichorionic twin delivery at term with cephalic-presenting first twin - a monocentric retrospective cohort study]. AB - OBJECTIVE: To assess neonatal outcome and delivery mode in dichorionic twin delivery at term with a cephalic-presenting first twin. METHODS: A retrospective cohort study of 308 twin deliveries after 37 completed weeks of gestation with a cephalic-presenting first twin undertaken in one perinatal center with active management of second twin delivery. The neonatal outcome was measured by the Apgar score, the umbilical artery pH and the transfer into the neonatal unit. RESULTS: In the whole group, 57% were vaginally delivered and 43% needed a Cesarean delivery. The planned vaginal delivery group contained 71% while the planned elective Cesarean delivery group contained 29%. In the planned vaginal delivery group 80% were delivered vaginally, in 15% an emergency Cesarean was necessary, 5% had a vaginal delivery of the first twin followed by Cesarean delivery of the second twin. The neonatal outcome of the second twin shows a higher risk. There are significant differences in the rates of the second twin having lower rates of the umbilical artery pH >7.20 in the group of planned vaginal delivery. The higher risks are compensated in the group of planned elective Cesarean delivery. CONCLUSIONS: Planned vaginal delivery of dichorionic twins at term and active second-stage management is associated with lower rate of normal neonatal outcome. These risks should be considered in prenatal informed consent discussions with the pregnant woman. PMID- 21031331 TI - [Fractures in neonates as a result of birth trauma caused by caesarean section]. AB - BACKGROUND: The occurrence of 4 bone fractures associated with birth by Caesarean section (CS) prompted us to examine the incidence and predisposing factors of bone injuries sustained during birth. CASE REPORT AND METHOD: The 4 cases with fractures were evaluated retrospectively and discussed in combination with a short review of the literature. CONCLUSIONS: With the increasing number of Caesarean sections the incidence of birth trauma has decreased. Nevertheless, when performing a CS there is still a risk of serious trauma to the neonate, including bone fractures. A Caesarean section for breech presentation constitutes a predisposition for femoral fractures. When diagnosed early and treated properly, the prognosis for these fractures is good without sequelae and one can expect a satisfactory clinical outcome for the child. We suggest that the possibility of this complication be mentioned when counselling the mother and getting informed consent. PMID- 21031332 TI - A novel device for islet transplantation providing immune protection and oxygen supply. AB - Islet transplantation as a biological beta-cell replacement therapy has emerged as a promising option for achieving restoration of metabolic control in type 1 diabetes patients. However, partial or complete loss of islet graft function occurs in relatively short time (months to few years) after implantation. The high rate of early transplant dysfunction has been attributed to poorly viable and/or functional islets and is mediated by innate inflammatory response at the intravascular (hepatic) transplant site and critical lack of initial nutrient/oxygen supply prior to islet engraftment. In addition, the diabetogenic effect of mandatory immunosuppressive agents, limited control of alloimmunity, and the recurrence of autoimmunity limit the long-term success of islet transplantation. In order to abrogate instant blood-mediated inflammatory reaction and to provide oxygen supply for the islet graft, we have developed an extravascular (subcutaneous) transplant macrochamber (the 'betaAir' device). This device contains islets immobilized in alginate, protected from the immune system by a thin hydrophilized teflon membrane impregnated with alginate and supplied with oxygen by daily refueling with oxygen-CO (2) mixture. We have demonstrated successful utilization of the oxygen-refueling macrochamber for sustained islet viability and function as well as immunoprotection after allogeneic subcutaneous transplantation in healthy minipigs. Considering the current limitations of intraportal islet engraftment and the restricted indication for islet transplantation mainly due to necessary immunosuppressive therapy, this work could very likely lead to remarkable improvements in the procedure and moreover opens up further strategies for porcine islet cell xenotransplantation. PMID- 21031333 TI - [The use of resorbable osteosynthesis materials]. AB - INTRODUCTION: Different materials can be used for fixation of fractures or for osteoplastic operations in head and neck surgery. Especially metallic and resorbable implants are at the market now. Advantages and disadvantages of the different implants should be considered as decisive for different indications. PATIENTS AND METHODS: We retrospectively analyzed the patients since 1999 which we operated using such resorbable materials. From 1999 until 2006 we used LactoSorb((r)). 2007 we introduced the Resorb X((r)) plates and -meshs and the SonicWeld Rx-System((r)). Here the plates or meshs will be fixed by an ultrasonically welded pin. RESULTS: In 52 cases we implanted LactoSorb((r)) and Resorb X((r)) with the SonicWeld Rx-System((r)). In 2 cases we saw a foreign body reaction that resulted in a fistula. In one case a plate broke after fixing. CONCLUSION: The use of resorbable materials with ultrasonically welded pin osteosynthesis resulted in a stable mechanical connection, an easy intraoperative handling and a low rate of complications. Those materials can be used for traumatologic and osteoplastic reconstructions in head and neck surgery. PMID- 21031334 TI - [MALT and the Epithelium of the Middle Ear Mucosa. Morphological Studies]. AB - INTRODUCTION: The mucosa of the middle ear and the Eustachian Tube changes in different ways when faced with recurrent episodes of inflammation. It thereby adapts to these new stimuli and insults from the environment. One of these changes is the development of MALT (mucosa associated lymphoid tissue). Another adaptation is an alteration of the epithelium. It was therefore the purpose of this study to look for a connection between the occurrence of these changes. MATERIAL AND METHODS: 90 sections of temporal bones were examined under the light microscope and the incidence of MALT and nature of the epithelium found were compared. RESULTS: Particularly in the middle ear, we demonstrated that in cases where MALT was found within the mucosa, columnar epithelium was frequently found in locations where it is typically rare. Squamous epithelium was in many cases replaced by cuboidal epithelium. DISCUSSION: We demonstrated that the mucosa of the middle ear changed its morphology towards the characteristics typically found in the upper respiratory tract in cases where MALT had developed as subepithelial lymphoid follicles. It can therefore be concluded that both changes represent the mucosa's reaction to recurrent or chronic inflammation. PMID- 21031335 TI - [Respiratory problems of unknown cause of a teacher and a veterinarian]. PMID- 21031336 TI - Isolation of 5-(hydroxymethyl)furfural from Lycium chinense and its inhibitory effect on the chemical mediator release by basophilic cells. AB - The effect of hot water extracts of LYCIUM CHINENSE fruits (LCF) on the beta hexosaminidase (beta-hexo) release by IgE sensitized BSA stimulated rat basophilic leukemia (RBL-2H3) cells was investigated. The ethylacetate (EtOAc) layer of the extract has shown an inhibitory effect on beta-hexo release from RBL 2H3 cells at the antigen antibody binding stage. The water (H2O) fraction (EFW) of the chloroform (CHCl3) extract from the EtOAc layer also inhibited beta-hexo release at the same stage in a dose-dependent manner. With column chromatography preparation, proton and carbon nuclear magnetic resonance (1H and 13C NMR) spectra, electron ionization mass spectrometer (EI-MS) spectra, and high performance liquid chromatography (HPLC) analysis, the active component was determined to be 5-(hydroxymethyl)furfural (5-HMF). Thus, the 5-HMF showed an inhibitory effect on beta-hexo release at the antigen-antibody binding stage and the antibody-receptor binding stage. Furthermore, 5-HMF suppressed [Ca2+] I influx in the IgE-sensitized BSA-stimulated RBL-2H3 cells. Our results show that 5-HMF may be useful for the treatment or prevention of type I allergic diseases. PMID- 21031337 TI - Carotid intima-media thickness and arterial stiffness in type 1 diabetic patients are dependent on age and mean blood pressure. AB - AIM: The aim of the study was to assess the factors that influence carotid intima media thickness (CIMT) and arterial stiffness in type 1 diabetic patients. MATERIAL AND METHODS: We included 87 type 1 diabetic patients (44 women, 43 men), median age 34 years, disease duration 10 years, HbA1c 8.2%. CIMT was measured using high resolution ultrasonography. Arterial stiffness was assessed with the use of digital volume pulse analysis and tonometric measurement of wave reflection and central haemodynamics. Serum C-reactive protein (hsCRP), matrix metalloproteinase-9 (MMP-9), soluble intracellular adhesion molecule-1 (sICAM-1) and myeloperoxidase (MPO) concentrations were also measured. RESULTS: CIMT and arterial stiffness correlated with age, duration of diabetes, systolic and diastolic blood pressure, GFR-glomerular filtration rate and sICAM-1. Multiple regression analysis identified only age as significant determinant of CIMT. Age, mean blood pressure and GFR, but not duration of diabetes were significant determinants of arterial stiffness. CONCLUSIONS: In type 1 diabetic patients both CIMT and arterial stiffness were related to age, blood pressure, kidney function and sICAM-1 serum concentration. PMID- 21031338 TI - The potential of bovine vaginal smear for biomarker development to trace the misuse of anabolic agents. AB - In the European Union the use of anabolic hormones in meat production is forbidden since 1988 and this ban of anabolic agents in animal production is strictly controlled. New hormone cocktails passing the detection systems are attractive for the practice and so new approaches to discover their illegal use have to be developed steadily. Verifying physiological effects caused by anabolic steroids will be a new way to develop potential monitoring systems. One promising matrix in female animals will be vaginal smear containing vaginal epithelial cells, because the vaginal epithelium is a primary steroid hormone responsive organ. In this study we quantified the gene expression in vaginal smear of sexually mature cattle in order to observe physiological effects. Further we aimed to establish a new screening method by testing the effect of a combination of certain anabolic steroid hormones on physiological regulations of mRNA expression of selected genes. In an animal trial Nguni heifers were treated with the anabolic combination trenbolone acetate plus estradiol. Vaginal smear samples were taken at 4 different time points. Gene expression of 27 candidate genes, selected by screening the actual literature for steroidal effects on vaginal epithelial cells, were estimated using quantitative real-time RT-PCR. There were different expression changes observed at different time points. It could be shown that the applied anabolic combination significantly influenced the expression of the steroid receptor ERalpha, the keratinization factor CK8, the proinflammatory interleukins IL-1alpha and IL-1beta, the growth factors FGF7, EGF, EGFR, IGF-1R, TGFalpha and LTF, the oncogen c-jun and other factors like actinbeta and ubiquitin 3. Using biostatistical tools like principal components analysis or hierarchical cluster analysis, the potential to develop a gene expression pattern for targeting the illegal use of growth promoters could be demonstrated. PMID- 21031339 TI - Obesity of TallyHO/JngJ mouse is due to increased food intake with early development of leptin resistance. AB - TALLYHO/JngJ (TallyHo) mouse is a recently established animal model for type 2 diabetes mellitus (T2DM) with phenotypes of mild obesity and male-limited hyperglycemia. In this study, we investigated how obesity develops in TallyHo mice by measuring parameters of food intake and energy expenditure. At 4 weeks of age, TallyHo mice were heavier than control C57BL/6 mice with increased food intake but comparable energy expenditure parameters, such as body temperature, cold-induced thermogenesis, oxygen consumption rate (VO(2)) and spontaneous locomotor activity. Furthermore, pair-fed TallyHo mice, which were fed the same amount of food as C57BL/6 mice, showed similar patterns of body weight gain to C57BL/6 mice at all ages, implying that obesity in TallyHo mice may develop by increased food intake but not by decreased energy consumption. TallyHo mice appear to have hypothalamic leptin resistance at 4 weeks of age, as indicated by the increased expression of orexigenic neuropeptides in the hypothalamus and no alteration of food intake and neuropeptide expression upon intravenous leptin treatment. Leptin injection to TallyHo mice, however, increased the phosphorylation of STAT3 and Akt, an important signaling mediator of leptin, in a pattern similar to that in C57BL/6 mice. In conclusion, increased food intake is a crucial component in the development of obesity in TallyHo mice, in which central leptin resistance, possibly caused by uncoupling between activation of leptin signaling and neuropeptide expression, might be involved. PMID- 21031340 TI - Are there gender-specific differences concerning quality of life in treated acromegalic patients? AB - OBJECTIVE: Acromegaly is associated with deleterious comorbidities that can remain irreversible even after successful cure has been achieved and lead to a persistently impaired Quality of Life (QoL). The aim of the study was to assess frequency and degree of persistent comorbidities and complaints after treatment of acromegaly and to investigate their impact on QoL. Another scope of interest was to determine gender-specific factors that influence perceived QoL in men and women. METHODS: We developed an Acromegaly Comorbidities & Complaints Questionnaire (ACCQ) consisting of 8 items (e. g. acral enlargement, joint complaints, hypertension, diabetes) known to affect QoL in order to assess frequency and degree of comorbidities. Additionally, the Acromegaly Quality of Life Questionnaire (AcroQoL) and the Short-form 36 (SF-36) questionnaire were handed out to 55 treated acromegalic patients. RESULTS: Both genders suffer from a lasting impairment in quality of life to a considerable degree. Complaints impairing manual skills (e. g. acral enlargement, arthralgias) were the most frequent findings (73% of all participants) in both genders. Multivariate analyses revealed that in men numbness of fingers and persistent joint-complaints were decisively responsible for impaired QoL. In women, it was the persistence of hypertension. CONCLUSIONS: Persistent joint complaints have adverse effects on QoL after treatment of acromegaly in men, possibly because they lead to impairment of manual motor skills and a handicap in their working life. Women seem to perceive late effects of hypertension as a manifest health threat. PMID- 21031341 TI - Sex differences in the development of diabetes in mice with deleted wolframin (Wfs1) gene. AB - Wolfram syndrome, caused by mutations in the wolframin (Wfs1) gene, is characterised by juvenile-onset diabetes mellitus, progressive optic atrophy, diabetes insipidus and deafness. Diabetes tend to start earlier in boys. This study investigated sex differences in longitudinal changes in blood glucose concentration (BGC) in wolframin-deficient mice (Wfs1KO) and compared their plasma proinsulin and insulin levels with those of wild-type (wt) mice. Non fasting BGC was measured weekly in 42 (21 males) mice from both groups at nine weeks of age. An intraperitoneal glucose tolerance test (IPGTT) was conducted at the 30 (th) week and plasma insulin, c-peptide and proinsulin levels were measured at the 32 (nd) week. At the 32 (nd) week, Wfs1KO males had increased BGC compared to wt males (9.40+/-0.60 mmol/l vs. 7.91+/-0.20 mmol/l; p<0.05). The opposite tendency was seen in females. Both male and female Wfs1KO mice had impaired glucose tolerance on IPGTT. Wfs1KO males had significantly lower mean plasma insulin levels than wt males (57.78+/-1.80 ng/ml vs. 69.42+/-3.06 ng/ml; p<0.01) and Wfs1KO females (70.30+/-4.42 ng/ml; p<0.05). Wfs1KO males had a higher proinsulin/insulin ratio than wt males (0.09+/-0.02 vs. 0.05+/-0.01; p=0.05) and Wfs1KO females (0.04+/-0.01; p<0.05). Plasma c-peptide levels in males were lower in Wfs1KO males (mean 55.3+/-14.0 pg/ml vs. 112.7+/-21.9 pg/ml; p<0.05). Male Wfs1KO mice had a greater risk of developing diabetes than female Wfs1KO mice. Low plasma insulin concentration with an increased proinsulin/insulin ratio in Wfs1KO males indicates possible disturbances in converting proinsulin to insulin which in long-term may lead to insulin deficiency. Further investigation is needed to clarify the mechanism for the sex differences in the development of diabetes in Wolfram syndrome. PMID- 21031342 TI - Expression of matrix-metalloproteases in the fluid of chronic diabetic foot wounds treated with a protease absorbent dressing. AB - It is well known, that wound healing in diabetes is impaired. Persistently high levels of matrix-metalloproteases (MMPs) contribute to wound persistence. The topical use of protease-inhibitors might beneficially affect wound healing. RESEARCH DESIGN AND METHODS: 19 patients with chronic diabetic foot lesions (Wagner/Armstrong 2A) were studied. 6 patients received "good standard wound care", 13 patients were treated with a protease-inhibitor-modulating-matrix (ORC/collagen matrix) that was changed daily. At day 1 and 5 biopsies were taken from the wounds; wound fluids were collected daily. Biopsies were analysed using quantitative real-time-PCR and all samples were analysed using ELISA and zymography for MMPs, TIMPs, IL 1-beta and TNFalpha levels. RESULTS: No differences in mRNA-expression of MMPs, TNFalpha and for MMP levels in wound tissue were detected between both groups or between the 2 sampling time points. MMP-2 active was significantly reduced in wound fluids of ORC/collagen treated lesions (p=0.043) after 5 days. MMP-2 pro was also reduced by about 25% when compared to increasing levels in the control group (+27%). We observed a significant reduction of the wound area in the ORC/collagen group (p=0.003). CONCLUSIONS: Local treatment with a protease-inhibitor has a beneficial effect on wound healing. In contrast to unchanged mRNA-levels and protein levels of MMPs there was a clear reduction of MMP-2-levels in wound fluids. Our data support the potential role of ORC/collagen as a wound dressing. Modulation of MMPs appears to be beneficial in the treatment of chronic diabetic wounds. PMID- 21031343 TI - Effects of rosiglitazone/metformin fixed-dose combination therapy and metformin monotherapy on serum vaspin, adiponectin and IL-6 levels in drug-naive patients with type 2 diabetes. AB - OBJECTIVE: Vaspin, adiponectin and interleukin-6 (IL-6) constitute novel adipose tissue derivatives, known as adipokines, which mediate insulin resistance. The aim of the present study was to evaluate the effects of metformin and rosiglitazone on serum levels of those novel adipokines in drug-naive patients with type 2 diabetes mellitus (T2DM). METHODS: 140 patients with T2DM, already treated with diet, but without adequate glycemic control (HbA1c > 7%), were randomly assigned to: RSG+MET group, (n = 70): Combination therapy with fixed dose of 4 mg rosiglitazone plus 500 mg metformin. MET group, (n = 70): Half maximum dose of metformin monotherapy (1 700 mg/day). Before and after 6-month treatment, body-mass index (BMI), blood pressure (BP), fat-mass, fasting plasma glucose (FPG), HbA1c, insulin resistance indexes (HOMA-IR, insulin), lipids, high sensitivity CRP (hsCRP), vaspin, adiponectin, and interleukin-6 (IL-6) were measured. RESULTS: Glucose regulation and insulin resistance were equivalently improved from baseline within both groups (p < 0.05). There was a considerable amelioration of hsCRP, WBC, adiponectin, IL-6, systolic and diastolic BP with rosiglitazone/metformin combined treatment as compared to baseline (p < 0.05) and MET group (p < 0.05). In contrast, metformin monotherapy significantly reduced BMI (p < 0.001), total-cholesterol (p = 0.012) and LDL (p = 0.020) levels compared to RSG+MET group. Importantly, serum vaspin concentration was equivalently decreased from baseline in both RSG+MET (-0.96 +/- 0.75 ng/ml, p < 0.001) and MET (-0.92 +/- 0.57 ng/ml, p=0.001) group. The aforementioned vaspin changes correlated with changes in WHR, HbA1c, FPG, HOMA-IR, insulin, IL-6 (only in the RSG+MET group) and fat-mass. In standard multiple regression analysis, FPG, HbA1c, HOMA-IR and insulin remained independent determinants of serum vaspin levels changes (R2 = 0.836, p = 0.004). CONCLUSIONS: Both rosiglitazone/metformin combination therapy and metformin monotherapy decreased serum vaspin levels through glucose and insulin sensitivity regulation, while they exerted differential effects on adiponectin, IL-6 and other cardiovascular risk factors in drug-naive patients with T2DM. PMID- 21031344 TI - Depressive symptoms, not completing a depression screening questionnaire, and risk of poor compliance with regular primary care visits in patients with type 2 diabetes: the Japan Diabetes Outcome Intervention Trial 2 (J-DOIT2) study group. AB - OBJECTIVES: To explore the association between depressive symptoms as measured by the Center for Epidemiologic Studies Depression Scale or not completing the questionnaire and subsequent risk of poor compliance with regular visits to primary care physician in patients with type 2 diabetes. METHODS: Using data from patients with type 2 diabetes who participated in the Japan Diabetes Outcome Intervention Trial 2 (J-DOIT2) Pilot Study, which was conducted at primary care settings, we examined the association between depressive symptoms or not completing the questionnaire and risk of poor compliance with regular visits as an event. RESULTS: Among 1 584 patients who participated in the J-DOIT2 Pilot Study, we excluded 140 who did not meet inclusion criteria or who declined participation after randomization, leaving 1 444 for entry in the present analysis. During 1 409 person-years of follow-up (median 1 year), 90 events were observed (incidence rate 63.9/1 000 person-years). The multivariable-adjusted hazard ratio of poor compliance with regular visits in those having depressive symptoms was 1.23 (95% CI: 0.46-3.31). In contrast, the multivariable-adjusted hazard ratio of poor compliance in those not completing the questionnaire was 2.26 (95% CI: 1.94-2.63). CONCLUSION: Not completing a questionnaire was significantly associated with an increased risk of poor compliance with the maintenance of regular visits to a primary care physician in patients with type 2 diabetes. Patients who do not comply with questionnaire surveys require increased attention to ensure their compliance with regular visits, and thereby ensure better diabetes outcomes. PMID- 21031345 TI - Comparison of antidepressant responses in patients with bipolar vs. unipolar depression: a meta-analytic review. AB - BACKGROUND: Since there is considerable uncertainty about therapeutic responses to antidepressants among depressed patients diagnosed with bipolar (BP) vs. unipolar (UP) mood disorders, we have reviewed available studies that compared both types of depressed patients. METHODS: Extensive computerized literature searching identified reports of antidepressant studies involving both BP and UP depressed patients. We used random-effects meta-analysis to compare short-term drug responses by patient type, as well as meta-regression modeling for effects of selected covariates. RESULTS: We identified only 10 studies meeting even liberal inclusion criteria, and they varied greatly in size and design quality. The overall difference in antidepressant responses between BP (n=863) and UP (n=2 226) disorder patients was not significant (pooled RR=1.05; CI: 0.96-1.15; P=0.34). Based on meta-regression, we also found no difference in responses based on diagnosis or subtype, subjects/study, % women, average age, or length of treatment based on meta-regression. Risk of manic-switching averaged 2.50 vs. 0.275%/week among BP vs. UP disorder patients, including co-treatment with mood stabilizers in 70% of BP patients. COMMENTS: The findings suggest little difference in antidepressant responses by diagnostic type, sex, or other factors considered, but a substantial risk of mania and hypomania with BP disorders. However, data pertaining to the fundamental question of antidepressant response among BP vs. UP depressed patients were strikingly limited, and support only tentative conclusions. Additional, well-designed, prospective trials of matched BP and UP depression patients and controlled treatment are required. PMID- 21031346 TI - Non-invasive prediction of intra-amniotic inflammation in women with preterm labor. AB - OBJECTIVE: To develop a model based on non-invasive variables to predict the probability of intra-amniotic inflammation in women with preterm labor and intact membranes. METHODS: Transvaginal ultrasonography and digital examination for the assessment of cervical length and cervical dilatation were performed, and maternal blood was collected for the determination of C-reactive protein and white blood cell (WBC) count immediately after amniocentesis in 153 consecutive women with preterm labor. Amniotic fluid obtained by amniocentesis was cultured for aerobic and anaerobic bacteria and mycoplasmas, and the WBC was determined. Intra-amniotic inflammation was defined as an elevated amniotic fluid interleukin 6 concentration (> 2.6 ng/mL). Receiver-operating characteristics (ROC) curves and logistic regression analysis were used for statistical analysis. RESULTS: The prevalence of a positive amniotic fluid culture was 7.2% (11/153) and the prevalence of intra-amniotic inflammation was 19.6% (30/153). The final logistic regression model was based on non-invasive clinical variables, including gestational age at assessment, cervical length and maternal blood WBC count, which were the best predictors of intra-amniotic inflammation. The model was shown to have an adequate goodness of fit (P = 0.754), and the area under the ROC curve was 0.724, indicating reasonably good discrimination. CONCLUSION: In women with preterm labor and intact membranes, the risk for intra-amniotic inflammation can be predicted non-invasively with a risk score based on gestational age, cervical length and maternal blood WBC count. PMID- 21031348 TI - Added value of three-/four-dimensional ultrasound in offline analysis and diagnosis of congenital heart disease. AB - OBJECTIVE: Many published studies have shown that application of three dimensional (3D) and real-time 3D (4D) ultrasound modalities can improve certain aspects of fetal echocardiography, but have left open the question of whether these modalities improved the accuracy of prenatal detection of anatomical fetal cardiovascular malformations. We aimed to determine whether 3D/4D ultrasound improved diagnostic ability in cases of congenital heart disease (CHD). METHODS: Women who attended for early- or midtrimester targeted organ scans had complete fetal echocardiography according to our five-planes protocol, as well as examination of the ductus venosus and longitudinal aortic arch planes, performed with 2D ultrasound combined with 2D color Doppler, spatiotemporal image correlation (STIC), STIC with color Doppler, and STIC with B-flow. Ultrasound data of cases of CHD were stored in a dedicated archive. Stored cases were anonymized and the list order was randomized. Stored 2D ultrasound cineloops and 4D ultrasound volumes were reviewed separately according to a standardized table of 23 specified structures on five required planes of visualization: the upper abdomen, four-chamber view, five-chamber view, pulmonary artery bifurcation view, and three vessels and trachea plane. Separate diagnoses were recorded and finally compared. Diagnoses were confirmed by pathological examination or neonatal echocardiography. RESULTS: During the study period, 13 101 examinations were performed; 181 diagnoses of CHD were made. In 12 of these, 3D/4D ultrasound added to the accuracy of our diagnosis: one right aortic arch with anomalous branching; one transposition of the great arteries with pulmonary atresia diagnosed with tomographic ultrasound imaging (TUI); one segmental interrupted aortic arch diagnosed with TUI; one right ventricle aneurysm diagnosed with B-flow; two agenesis of ductus venosus to the coronary sinus diagnosed by multiplanar reconstruction (MPR) and B-flow; two total anomalous pulmonary venous connection diagnosed with MPR; and four ventricular septal defect (VSD) diagnosed with the aid of virtual planes. There were 12 missed diagnoses and no false-positive results. CONCLUSIONS: 3D/4D ultrasound modalities may have advantages in some aspects of fetal cardiovascular evaluation, however, overall 3D/4D ultrasound modalities had added value in only about 6% of cases of fetal anatomical cardiovascular anomalies. PMID- 21031359 TI - Physico-chemical and structural changes of red-fleshed dragon fruit (Hylocereus polyrhizus) during fruit development. AB - BACKGROUND: Determination of physico-chemical (weight, length, diameter, stomatal density, respiration rate, colour, soluble solids concentration, titratable acidity, chlorophyll and betacyanin content) and structural changes of red fleshed dragon fruit (Hylocereus polyrhizus (Weber) Britton & Rose) was carried out from 5 to 35 days after pollination (DAP) in order to explain their growth, development, maturations and ripening stages. RESULTS: Fruit growth of red fleshed dragon fruit followed a sigmoid growth pattern. Significant changes in colour were obtained in both peel and pulp as DAP progressed, which were indicated by reductions of L*, C* and h degrees values as both changed from green to red-violet colour at ripening. Red-violet betacyanin was manifested earlier in pulp at 25 DAP, followed by peel 4-5 days later, and finally both peel and pulp turned full red-violet by 30 DAP. There was a significant increase in soluble solids concentration and titratable acidity with the continuous increase in betacyanin content as DAP progressed. CONCLUSION: The physico-chemical and betacyanin accumulation of red-fleshed dragon fruit changed as it developed, matured and ripened which coincided with structural changes. PMID- 21031351 TI - Ultrasound evaluation of the Cesarean scar: relation between a niche and postmenstrual spotting. AB - OBJECTIVE: To evaluate the relationship between a niche and abnormal uterine bleeding, and to develop a sonographic classification of niches and evaluate its relationship to abnormal uterine bleeding. METHODS: An observational prospective cohort study was performed between October 2007 and May 2009. All women who had a Cesarean section performed in our hospital were asked to participate. Two hundred and twenty-five women were included and examined with both transvaginal sonography (TVS) and gel instillation sonohysterography (GIS) 6-12 months after the Cesarean section. In case of a niche, the depth, volume and residual myometrium were measured, and the shape was assessed according to a specified classification. A questionnaire and pictorial blood loss assessment chart were filled in. RESULTS: The prevalence of a niche on evaluation with TVS and GIS was 24.0% and 56.0%, respectively. A niche was considered to be present if the depth was at least 1 mm visualized with GIS. Postmenstrual spotting was reported by 33.6% of women with a niche and 15.2% of women without a niche (P = 0.002). The niche volume was significantly different between women with and without postmenstrual spotting (P = 0.02). Most niches had a semicircular (50.4%) or triangular shape (31.6%). No significant relationship was identified between the shape of the niche and postmenstrual spotting (P = 0.19). CONCLUSIONS: A niche is present in 56.0% of women with a history of Cesarean section when examined by GIS and is associated with postmenstrual spotting. Semicircular and triangular niches are most common, but the shape is not related to postmenstrual spotting. PMID- 21031360 TI - Non-covalent interactions of alkali metal cations with singly charged tryptic peptides. AB - The complexes formed by alkali metal cations (Cat(+) = Li(+), Na(+), K(+), Rb(+)) and singly charged tryptic peptides were investigated by combining results from the low-energy collision-induced dissociation (CID) and ion mobility experiments with molecular dynamics and density functional theory calculations. The structure and reactivity of [M + H + Cat](2+) tryptic peptides is greatly influenced by charge repulsion as well as the ability of the peptide to solvate charge points. Charge separation between fragment ions occurs upon dissociation, i.e. b ions tend to be alkali metal cationised while y ions are protonated, suggesting the location of the cation towards the peptide N-terminus. The low-energy dissociation channels were found to be strongly dependant on the cation size. Complexes containing smaller cations (Li(+) or Na(+)) dissociate predominantly by sequence-specific cleavages, whereas the main process for complexes containing larger cations (Rb(+)) is cation expulsion and formation of [M + H](+). The obtained structural data might suggest a relationship between the peptide primary structure and the nature of the cation coordination shell. Peptides with a significant number of side chain carbonyl oxygens provide good charge solvation without the need for involving peptide bond carbonyl groups and thus forming a tight globular structure. However, due to the lack of the conformational flexibility which would allow effective solvation of both charges (the cation and the proton) peptides with seven or less amino acids are unable to form sufficiently abundant [M + H + Cat](2+) ion. Finally, the fact that [M + H + Cat](2+) peptides dissociate similarly as [M + H](+) (via sequence-specific cleavages, however, with the additional formation of alkali metal cationised b ions) offers a way for generating the low-energy CID spectra of 'singly charged' tryptic peptides. PMID- 21031361 TI - Electron transfer dissociation coupled to an Orbitrap analyzer may promise a straightforward and accurate sequencing of disulfide-bridged cyclic peptides: a case study. PMID- 21031362 TI - High hole mobility for a side-chain liquid-crystalline smectic polysiloxane exhibiting a nanosegregated structure with a terthiophene moiety. AB - Side-chain liquid-crystalline siloxane polymers bearing terthiophene moieties as mesogenic pendant groups have been synthesized. An alkenylterthiophene derivative was treated with poly(hydrogenmethylsiloxane) and poly(dimethylsiloxane-co hydrogenmethylsiloxane)s in Me(2)SiO/MeHSiO ratios of 1:1 and 7:3, respectively, in the presence of the Karstedt catalyst, to produce pale yellow polymers. The degrees of introduction of the mesogenic unit were 100, 50, and 30%, respectively. The polymers exhibit ordered smectic phases at room temperature. The copolymers with dimethylsiloxane units form smectic phases as a consequence of nanosegregation between the mesogenic units and siloxane backbones with the alkylene spacers. Time-of-flight measurement reveals that the hole mobility exceeds 1*10(-2) cm(2) V(-1) s(-1) in the ordered smectic phase of the copolymer with a degree introduction of the mesogenic units of 50%. This value is comparable to that of the highly ordered mesophases of low-molecular-weight derivatives of phenylnaphthalene and terthiophene. Because of the segregation behavior induced by the flexible backbone, a closer molecular packing structure favorable for fast carrier transport may be formed in the smectic phase of the copolymer in spite of the low density of the mesogenic groups. PMID- 21031363 TI - Generation and reactions of oxiranyllithiums by use of a flow microreactor system. AB - A flow microreactor system consisting of micromixers and microtubes provides an effective reactor for the generation and reactions of aryloxiranyllithiums without decomposition by virtue of short residence time and efficient temperature control. The deprotonation of styrene oxides with sBuLi can be conducted by using the flow microreactor system at -78 or -68 degrees C (whereas much lower temperatures (< -100 degrees C) are needed for the same reactions conducted under macrobatch conditions). The resulting alpha-aryloxiranyllithiums were allowed to react with electrophiles in the flow microreactor system at the same temperature. The sequential introduction of various electrophiles onto 2,3 diphenyloxiranes was also achieved by using an integrated flow microreactor, which serves as a powerful system for the stereoselective synthesis of tetrasubstituted epoxides. PMID- 21031364 TI - Integrated palladium-catalyzed arylation of heavier Group 14 hydrides. AB - A convenient procedure has been developed for the preparation of Group 14 compounds by integrated palladium-catalyzed cross-coupling of aromatic iodides with the corresponding Group 14 hydrides in the presence of a base. The reaction conditions can be applied to the cross-coupling of tertiary, secondary, and primary Group 14 compounds. In most cases, the desired arylated products were obtained in synthetically useful yields. Even in the case of aryl iodides containing OH, NH(2), CN, or CO(2)R groups, the reactions proceeded with good to high yields with tolerance of these reactive functional groups. A possible application of this method is the unique synthesis of a fungicidal diarylmethyl(1H-1,2,4-triazol-1-ylmethyl)silane derivative. PMID- 21031369 TI - A highly efficient and extensively reusable "dip catalyst" based on a silver nanoparticle-embedded polymer thin film. AB - Achieving a harmonious combination of the efficiency of homogeneous catalysts with the reusability of heterogeneous catalysts is a fundamental and challenging problem. Metal nanoparticles in a suitable matrix offer a potential solution. However an ideal design is yet to be realized, because the critical requirements of facile access to the catalyst, its durability, and ease of retrieval and reuse are difficult to reconcile. We report herein a multilayer free-standing thin-film catalyst based on silver nanoparticles, generated in situ inside poly(vinyl alcohol) by using a facile protocol, which shows excellent efficiency and extensive reusability in the prototypical reaction, the reduction of 4 nitrophenol by sodium borohydride. The "dip catalyst" film, which can start/stop the reaction instantaneously by mere insertion/removal, is used 30 times leading to a total turnover number (TON) of ~3390, which is unprecedented for this reaction. The efficiency of the catalyst is reduced only marginally at the end of these runs, promising further extended usage. The unique advantage of convenient catalyst monitoring is illustrated by the periodic spectroscopic and microscopic examinations of the thin film, which revealed the basis of its durability. The demonstrated potential of metal-nanoparticle-embedded polymer thin films, coupled with their versatility and ease of fabrication, promises extensive applications in chemical catalysis. PMID- 21031370 TI - A neutral zwitterionic molecular solid. AB - We report on the acid ethylenedithiotetrathiafulvaleneamidoglycine (EDT-TTF-CO-NH CH(2)-CO(2)H; 1; EDT-TTF=ethylenedithiotetrathiafulvalene) and the 1:1 adduct [(EDT-TTF)(.+)-CO-NH-CH(2)-(CO(2))(-)][(EDT-TTF)-CO-NH-CH(2)-(CO(2)H)].CH(3)OH (2), a new type of hydrogen-bonded, 1:1 acid/zwitterion hybrid embrace of redox peptidics into a two-dimensional architecture, an example of a system deliberately fashioned so that oxidation of pi-conjugated cores toward the radical-cation form would interfere with the activity of the appended ionizable residues in the presence of a templating base during crystal growth. First principles calculations demonstrate that, notwithstanding preconceived ideas, a metallic state is more stable than the hole-localized alternatives for a neat 1:1 neutral acid/zwitterion hybrid. The inhomogeneous Coulomb field associated with proton-shared, interstacks O-H...O hydrogen bonds between the ionizable residues distributed on both sides of the two-dimensional pi-conjugated framework leads, however, to a weak hole localization responsible for the activated but high conductivity of 1 S cm(-1). This situation is reminiscent of the role of the environment on electron transfer in tetraheme cytochrome c, in which the protonation state of a heme propionate becomes paramount, or ion-gated transport phenomena in biology. These observations open rather intriguing opportunities for the construction of electronic systems at the interface of chemistry and biology. PMID- 21031371 TI - Rotaxanes capable of recognising chloride in aqueous media. AB - A new, versatile chloride-anion-templating synthetic pathway is exploited for the preparation of a series of eight new [2]rotaxane host molecules, including the first sulfonamide interlocked system. (1)H NMR spectroscopic titration investigations demonstrate the rotaxanes' capability to selectively recognise the chloride anion in competitive aqueous solvent media. The interlocked host's halide binding affinity can be further enhanced and tuned through the attachment of electron-withdrawing substituents and by increasing its positive charge. A dicationic rotaxane selectively binds chloride in 35% water, wherein no evidence of oxoanion binding is observed. NMR spectroscopy, X-ray structural analysis and computational molecular dynamics simulations are used to account for rotaxane formation yields, anion binding strengths and selectivity trends. PMID- 21031372 TI - Enantioselective synthesis of coumarins catalyzed by a bifunctional amine thiourea catalyst. PMID- 21031373 TI - Interaction of the human prion protein PrP106-126 with metal complexes: potential therapeutic agents against prion disease. PMID- 21031374 TI - Highly efficient synthesis of UDP-GalNAc/GlcNAc analogues with promiscuous recombinant human UDP-GalNAc pyrophosphorylase AGX1. PMID- 21031375 TI - Porous lithium imidazolate frameworks constructed with charge-complementary ligands. PMID- 21031377 TI - Oxetanes as versatile elements in drug discovery and synthesis. AB - Sizable resources, both financial and human, are invested each year in the development of new pharmaceutical agents. However, despite improved techniques, the new compounds often encounter difficulties in satisfying and overcoming the numerous physicochemical and many pharmacological constraints and hurdles. Oxetanes have been shown to improve key properties when grafted onto molecular scaffolds. Of particular interest are oxetanes that are substituted only in the 3 position, since such units remain achiral and their introduction into a molecular scaffold does not create a new stereocenter. This Minireview gives an overview of the recent advances made in the preparation and use of 3-substituted oxetanes. It also includes a discussion of the site-dependent modifications of various physicochemical and biochemical properties that result from the incorporation of the oxetane unit in molecular architectures. PMID- 21031376 TI - Synthesis of macrocyclic tetrazoles for rapid photoinduced bioorthogonal 1,3 dipolar cycloaddition reactions. PMID- 21031378 TI - Cisplatin: polymorphism and structural insights into an important chemotherapeutic drug. PMID- 21031379 TI - A bond by any other name. PMID- 21031380 TI - Selective catalytic oxidation of glycerol to dihydroxyacetone. PMID- 21031381 TI - Characterizing early aggregates formed by an amyloidogenic peptide by mass spectrometry. PMID- 21031382 TI - A highly efficient strategy for modification of proteins at the C terminus. PMID- 21031383 TI - Superresolution optical fluctuation imaging with organic dyes. PMID- 21031384 TI - Amphiphilic graphene composites. PMID- 21031385 TI - Enantioselective hydrogenation with chiral frustrated Lewis pairs. PMID- 21031387 TI - Luminescent sensing of oxygen using a quenchable probe and upconverting nanoparticles. PMID- 21031386 TI - One-step modification of superhydrophobic surfaces by a mussel-inspired polymer coating. PMID- 21031388 TI - The combined synthesis and coloration of poly(lactic acid). PMID- 21031389 TI - Alkyne-stabilized ruthenium nanoparticles: manipulation of intraparticle charge delocalization by nanoparticle charge States. PMID- 21031390 TI - Total synthesis of tryprostatins A and B. PMID- 21031391 TI - Redox-induced palladium migrations that allow reversible topological changes between palladium(II) complexes of Mobius aromatic [28]hexaphyrin and Huckel aromatic [26]hexaphyrin. PMID- 21031392 TI - Towards the isomer-specific synthesis of higher fullerenes and buckybowls by the surface-catalyzed cyclodehydrogenation of aromatic precursors. PMID- 21031393 TI - Activation of Si-H, B-H, and P-H bonds at a single nonmetal center. PMID- 21031394 TI - The [4+2], not [2+2], mechanism occurs in the gold-catalyzed intramolecular oxygen transfer reaction of 2-alkynyl-1,5-diketones. PMID- 21031397 TI - Charles H. Stone Award: J.-L. Bredas / Izatt-Christensen Award: L. Fabbrizzi / Organic Chemistry Young Investigator Awards: H.-D. Arndt and N. Cramer. PMID- 21031395 TI - Orthogonal protein decoration of DNA origami. PMID- 21031398 TI - From noble metal to Nobel Prize: palladium-catalyzed coupling reactions as key methods in organic synthesis. PMID- 21031399 TI - A strategy for designing a peptide probe for detection of beta-amyloid oligomers. AB - Aggregation of beta-amyloid (Abeta) is implicated in the pathology of Alzheimer's disease. Development of a robust strategy to detect Abeta oligomeric intermediates, which have been identified as significant toxic agents, would be highly beneficial in the screening of drug candidates as well as enhancing our understanding of Abeta oligomerization. Rapid, specific and quantitative detection, currently unavailable, would be highly preferred for accurate and reliable probing of transient Abeta oligomers. Here, we report the development of a novel peptide probe, PG46, based on the nature of Abeta self-assembly and the conformation-sensitive fluorescence of the biarsenical dye, FlAsH. PG46 was found to bind to Abeta oligomers and displayed an increase in FlAsH fluorescence upon binding. No such event was observed when PG46 was co-incubated with Abeta low molecular-weight species or Abeta fibrils. Abeta oligomer detection was fast, and occurred within one hour without any additional sample incubation or preparation. We anticipate that the development of a strategy for detection of amyloid oligomers described in this study will be directly relevant to a host of other amyloidogenic proteins. PMID- 21031400 TI - DNAzyme-like activity of hemin-telomeric G-quadruplexes for the optical analysis of telomerase and its inhibitors. PMID- 21031401 TI - Organosilica spheres covalently functionalized with diphenylanthracene and viologen units. AB - Organosilica spheres functionalized with two different photoactive units, diphenylanthracene, DPA@SPH, and viologen, VIO@SPH, covalently linked to the silica framework are prepared. These new materials have a uniform diameter, 300 nm for the DPA@SPH and 550 nm for the VIO@SPH, and exhibit the typical photochemical response of the organic moieties. It is observed that organic radical cations incorporated in the structure of the functionalized silica spheres are remarkably persistent. Due to their morphology and regular diameter DPA@SPH do not tend to aggregate and they form a highly regular, ordered and homogeneous multilayer film of high surface coverage which is employed as the active layer for the preparation of an electroluminescence cell. PMID- 21031403 TI - Electroluminescence from individual pentacene nanocrystals. PMID- 21031414 TI - Appendiceal carcinoid tumors: Predictors of lymph node metastasis and the impact of right hemicolectomy on survival. AB - BACKGROUND AND OBJECTIVES: Given the lack of population-based data in the literature, we sought to (1) identify predictors of appendiceal carcinoid tumor nodal metastasis to distinguish which patients would most likely benefit from hemicolectomy and (2) compare survival after hemicolectomy versus appendectomy alone. METHODS: Using the Surveillance Epidemiology and End Results Database (1988-2005), we identified patients with appendiceal carcinoid tumors who underwent resection. We identified risk factors for nodal metastasis using logistic regression models and used the Kaplan-Meier method to compare adjusted overall and cancer-specific survival after right hemicolectomy versus appendectomy alone. RESULTS: 576 patients met our inclusion criteria. We found that tumor size (>2.0 cm) and tumor histology (pure carcinoid tumors) were significant predictors of lymph node metastasis. After stratifying by tumor size, we did not detect a significant difference in survival between patients who underwent hemicolectomy and those that underwent appendectomy alone (log-rank, P > 0.10). CONCLUSIONS: Tumor size and histology are significant predictors of appendiceal carcinoid tumor nodal metastasis and therefore may be helpful to identify which patients would most likely benefit from a hemicolectomy. However, our population-based study did not demonstrate a significant difference in adjusted survival rates between hemicolectomy versus appendectomy alone. PMID- 21031415 TI - Prognostic significance of expression of VEGF and Cox-2 in nasopharyngeal carcinoma and its association with expression of C-erbB2 and EGFR. AB - BACKGROUND AND OBJECTIVES: This study evaluated several tumor angiogenesis related markers to examine their expression pattern and relation to clinicopathologic implications of nasopharyngeal carcinoma. METHODS: Paraffin sections from 69 nasopharyngeal carcinomas obtained before radiotherapy were prepared. The expression of vascular endothelial growth factor (VEGF), cyclooxygenase-2 (Cox-2), C-erbB2, and epidermal growth factor receptor (EGFR) were investigated by immunohistochemistry and then correlated with various clinicopathologic parameters. RESULTS: VEGF was inversely correlated with C-erbB2 (P = 0.036). In survival analysis, high mitosis (>=5/10 high power field) was significantly associated with worse relapse-free survival in univariate analysis (P = 0.048) but not in multivariate analysis (P = 0.153). High stage, high mitotic rate, absence of VEGF, and presence of Cox-2 were associated with worse survival in both univariate analysis (P = 0.002, P = 0.038, P = 0.044, and P = 0.028, respectively) and multivariate analysis (P = 0.007, P = 0.036, P = 0.047, and P = 0.004, respectively). CONCLUSIONS: Absence of VEGF is a useful indicator of poor prognosis in addition to Cox-2 expression, high stage, and high mitosis. PMID- 21031419 TI - Far from solved: a perspective on what we know about early mechanisms of left right asymmetry. AB - Consistent laterality is a crucial aspect of embryonic development, physiology, and behavior. While strides have been made in understanding unilaterally expressed genes and the asymmetries of organogenesis, early mechanisms are still poorly understood. One popular model centers on the structure and function of motile cilia and subsequent chiral extracellular fluid flow during gastrulation. Alternative models focus on intracellular roles of the cytoskeleton in driving asymmetries of physiological signals or asymmetric chromatid segregation, at much earlier stages. All three models trace the origin of asymmetry back to the chirality of cytoskeletal organizing centers, but significant controversy exists about how this intracellular chirality is amplified onto cell fields. Analysis of specific predictions of each model and crucial recent data on new mutants suggest that ciliary function may not be a broadly conserved, initiating event in left right patterning. Many questions about embryonic left-right asymmetry remain open, offering fascinating avenues for further research in cell, developmental, and evolutionary biology. PMID- 21031420 TI - Analysis of 151 consecutive gastric submucosal tumors according to tumor location. AB - BACKGROUND: The aim of the present study was to evaluate the histopathological characteristics of gastric submucosal tumors (SMTs) according to their location. METHODS: A retrospective analysis of a prospective database of 151 consecutive patients who underwent surgery for gastric SMTs between 2001 and 2009 was performed. RESULTS: Of 151 gastric SMTs, 100 (66.2%) were gastrointestinal stromal tumors, 21 (13.9%) were leiomyomas, and 30 (19.9%) were other benign tumors. Leiomyoma was the most common neoplasm at the cardia (55.2%; P < 0.05), and the incidence of endophytic cardia tumors was higher compared with other locations (65.5%; P < 0.05). SMTs located at the cardia were significantly smaller than those found in the upper third (2.6 +/- 1.0 vs. 4.1 +/- 3.0; P < 0.05) and middle third (2.6 +/- 1.0 vs. 3.9 +/- 3.3; P < 0.05) of the stomach. CONCLUSIONS: The characteristics of gastric SMTs located at the cardia differ significantly from those of gastric SMTs located in other regions of the stomach. These findings suggest that treatment strategy should be tailored by the location of tumors. PMID- 21031422 TI - Genetic alterations of K-ras may reflect prognosis in stage III colon cancer patients below 60 years of age. AB - PURPOSE: Genetic alterations that are closely associated with patient prognosis can be landmarks of definitive therapeutic targets as well as useful biomarkers in human cancer clinics. METHODS: Three hundred seventy-eight colorectal cancer (CRC) patients were examined for K-ras mutations by single-strand conformation polymorphism (SSCP), with a subsequent 144 young colon cancer (YCC) patients added to validate its prognostic significance. RESULTS: K-ras mutations were identified in 161 (43%) of the 378 CRC patients and were significantly associated with tumor location (colon vs. rectum; 80/218 = 37% vs. 81/160 = 51%; P = 0.0068) and age (>=60 vs. <60; 103/220 = 47% vs. 58/158 = 37%; P = 0.049). The incidence of K-ras mutations was 30% in YCC patients as compared to 55% in elderly rectal cancer patients (P = 0.0004). K-ras mutations significantly correlated with a worse prognosis (P = 0.0014) only in 73 curatively resected YCC with stages I III, but not in other CRCs, which was further validated in the independent set of the corresponding 144 YCC patients (P = 0.024). Both univariate and multivariate analyses identified K-ras mutations as an independent prognostic factor (HR = 5.5, P = 0.029; HR = 3.6, P = 0.011) in both learning and validation sets of the curatively resected YCC with stages I-III, respectively, and the prognostic relevance was marked in stage III YCC patients (P = 0.002), but not in stages I, II, and IV. CONCLUSION: In curative YCC, K-ras mutations could have excellent prognostic value. Hence, the K-ras mutation status could be a good indicator to predict the clinical outcome in curatively resected stage III YCC patients, and K ras pathway inhibition may be a relevant therapeutic target in CRC, excluding YCC patients with no K-ras mutation. PMID- 21031424 TI - Oxaliplatin-based hyperthermic intraperitoneal chemotherapy in primary or recurrent epithelial ovarian cancer: A pilot study of 31 patients. AB - BACKGROUND: The feasibility and safety of oxaliplatin-based hyperthermic intraperitoneal chemotherapy (HIPEC) associated with cytoreductive surgery (CRS) was assessed in patients with peritoneal carcinomatosis resulting from primary advanced or relapsing epithelial ovarian cancer (EOC). METHODS: Thirty-one patients received neoadjuvant platin-based chemotherapy followed by oxaliplatin based HIPEC associated with CRS as consolidation of primary therapy (n = 19) or for relapsing disease (n = 12). Grade 3/4 complications were recorded according to National Cancer Institute definitions. RESULTS: Median peritoneal carcinomatosis index (PCI) was 2.7 after neoadjuvant chemotherapy. Mean duration of surgery was 352 min (range 105-614) and median hospital stay was 11 days (range 6-87). Grade 3 toxicity was observed in nine patients: five required repeat surgery, two an invasive procedure, four rehospitalization, and three a return to the ICU. No grade 4 toxicity occurred, excepted one hypokalemia. Median progression-free survival (PFS) for primary advanced EOC was 13.2 months and 1 year PFS was 59.3%. Median PFS for relapsing patients was 14.3 months and 1-year PFS was 54.4%. CONCLUSION: CRS with oxaliplatin-based HIPEC is feasible and relatively safe in recurrent and primary EOC. HIPEC after neoadjuvant chemotherapy reduces the PCI and decreases the number of surgical procedures and morbidity. Further evaluations of this procedure are required to assess the survival benefits. PMID- 21031425 TI - Conformal radiofrequency ablation of hepatocellular carcinoma with a multi-pin bipolar system. AB - BACKGROUND: To retrospectively evaluate the effectiveness and safety of radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) with a multi-pin bipolar system. METHODS: Between August 2005 and December 2006, 18 patients with 30 HCCs (3.40 +/- 1.24 cm, range 1.30-6.0 cm; median number of treated lesions is two per patient, range, 1-3) underwent percutaneous RFA with a multi-pin bipolar system under ultrasound guidance. The primary end-point were treatment efficacy, major and minor complications, and the secondary end-point were overall survival and tumor-free survival. RESULTS: Complete ablation with conformed shape to the index tumor was achieved in 16 of 18 patients, and 28 of the 30 tumors were completely ablated. On follow-up, local and distant intrahepatic tumor progression rates were 12.5% (2 of 16 patients) and 62.5% (10 of 16 patients). There was no patient who developed extrahepatic metastasis. There were no major complications. The 1-, 2-year overall survival rates for all patients were 83.3%, 55.6%, respectively, and the corresponding tumor-free survivals were 50.0%, 22.2%, respectively. CONCLUSION: RFA with a multi-pin bipolar system was effective and safe for HCC. A large ablation volume could be achieved which conformed to the shape of the index tumor. PMID- 21031427 TI - Elevated serum CRP levels after induction chemoradiotherapy reflect poor treatment response in association with IL-6 in serum and local tumor site in patients with advanced esophageal cancer. AB - BACKGROUND AND OBJECTIVES: Elevated serum CRP levels are associated with tumor progression and poor prognosis of esophageal cancer. The aim of this study was to clarify the clinical significance of CRP in relation to response to chemoradiotherapy in patients with esophageal cancer. METHODS: The relationship between serum CRP levels and response to chemoradiotherapy and prognosis was analyzed in 34 patients with advanced esophageal squamous cell carcinoma who underwent induction chemoradiotherapy followed by surgery. The relationship between response to chemoradiotherapy and interleukin-6 (IL-6) expression in sera and tumor tissues was also analyzed. RESULTS: Although elevated serum CRP levels were associated with poor response to chemoradiotherapy, significant difference in CRP levels between pathological responders (n = 18) and non-responders (n = 16) was observed after chemoradiotherapy, but not before. Patients with elevated CRP levels had shorter cause-specific survival, but significant difference was observed only after chemoradiotherapy. In addition, serum levels of IL-6 were also associated with poor treatment response following chemoradiotherapy and were correlated with residual tumor volume. IL-6 expression was detected in residual tumor tissues by immunohistochemistry. CONCLUSIONS: Elevated serum CRP levels after chemoradiotherapy may predict poor response to chemoradiotherapy more accurately than before chemoradiotherapy, and IL-6 may be a possible target associated with chemoradiotherapy resistance. PMID- 21031428 TI - Lateral approach to central compartment of neck. AB - Revision surgery in central compartment of neck is often a challenge for the head and neck surgical oncologists/endocrine surgeons. This is often required for completion thyroidectomies, central compartment lymph node dissections, and re exploration for persistent hyperparathyroidism. Scarring in midline due to prior surgery makes midline access to central compartment difficult and increases the risk of injury to recurrent laryngeal nerve and parathyroid glands. This article describes a simple technique of approaching central compartment between sternocleidomastoid and strap muscles. PMID- 21031429 TI - Adverse prognosis of clustered-cell versus single-cell micrometastases in pN0 early gastric cancer. AB - BACKGROUND AND OBJECTIVES: The clinical significance of lymph node micrometastasis (MM) for pN0 early gastric cancer is not well documented. The aim of this study is to clarify the risk factors of lymph node MM and the prognostic significance of the type of lymph node MM in patients with pN0 early gastric cancer. METHODS: We investigated the lymph node MM with using an anticytokeratin immunohistochemical stain in 160 patients with pN0 early gastric cancer who underwent curative resection between 2000 and 2005. RESULTS: We identified lymph node MM in 34 of 160 patients (21.3%), and in 84 of 1,656 lymph nodes (5.1%). MM occurred as single-cell type in 10 patients and as cell cluster type in 24 patients. MM was significantly associated with tumor size (P = 0.041) and lymphatic invasion (P = 0.008). The statistically significant prognostic factors affecting 5-year survival rates were depth of tumor invasion (P = 0.020), tumor size (P = 0.035), lymphatic invasion (P = 0.018), MM (P < 0.001), and type of MM (P < 0.001). Cox regression survival analysis revealed that the presence of MM, and particularly the cluster-type MM (P < 0.001), were independent prognostic factors in pN0 early gastric cancer patients. CONCLUSIONS: The incidence of lymph node MM in patients with node negative early gastric cancer was 21.3%, and cancer cell cluster type of MM proved a primary independent prognostic factor for pN0 early gastric cancer patients. PMID- 21031430 TI - Concurrent pheochromocytoma and cortical carcinoma of the adrenal gland. PMID- 21031431 TI - Blind cave salamanders age very slowly: a new member of Methuselah's Bestiary. PMID- 21031432 TI - Bead-based protein-protein interaction assays for the analysis of Rho GTPase signaling. AB - Bead-based interaction assays are excellently suited to study protein-protein interactions, as they require only minimal amounts of sample material. Miniaturized protein-protein interaction assays were designed to analyze Rho GTPase activation based on its interaction with Rho GDI or p21-activated kinase (PAK).Rho GDI plays a key role in the regulation of a variety of cellular functions through its interaction with Rho GTPases. Rho GDI is frequently overexpressed in many human cancers. Therefore, there is a growing and as yet unfulfilled demand for screening assays to identify biologically active compounds that may inhibit the Rho GTPase-Rho GDI interaction. Bead-based interaction assays provide an interesting alternative that facilitate such assays to be performed faster with only small amounts of material compared to routinely used co-immunoprecipitation followed by Western Blot analysis.Bead-based protein interaction assays for overexpressed HA-tagged Rho GTPases were established to study the GTPgammaS-dependent interaction of five different Rho GTPases with the regulatory protein Rho GDIalpha and the downstream effector PAK1. In addition, it was demonstrated that the ability of Rho GTPases to interact with Rho GDI in this experimental system was markedly, but differentially sensitive to post translational modification of their carboxyl terminus. Importantly, this modification also notably affected the ability of Rac1 and Rac2, but not of Cdc42, to interact with PAK1. PMID- 21031433 TI - Co-purification of Mac-2 binding protein with galectin-3 and association with prostasomes in human semen. AB - BACKGROUND: Prostasomes are exosome-like vesicles that are secreted by the prostate and incorporated into semen during ejaculation. Human prostasomes are proposed to function in regulation of sperm function, immunosuppression, and prostate cancer progression. Previously, we identified galectin-3 on the surface of prostasomes. Galectin-3 is a beta-galactoside binding protein involved in immunomodulation, cell interactions, and cancer progression, including prostate cancer. Functional characterization of galectin-3 in a given biological environment includes identification of its target glycoprotein ligands. METHODS: Candidate galectin-3 ligands in prostasomes were identified by tandem mass spectrometry of proteins that co-purified with galectin-3 during lactose affinity chromatography. Immunochemical and biochemical methods were used to investigate the association of Mac-2 binding protein (M2BP) with prostasomes. RESULTS: Proteins identified by tandem mass spectrometry included M2BP, CD26/dipeptidyl peptidase IV, prolactin-inducible protein (PIP), olfactomedin-4 (OLFM4), and semenogelins I and II (SgI and SgII). M2BP is a known galectin-3 ligand that was not previously described in prostasomes. M2BP protein bands were detected in the testis, epididymis, vas deferens, prostate, seminal vesicle, and sperm extracts. In seminal plasma, M2BP was identified in the soluble fraction and in purified prostasomes. Surface biotinylation and immunofluorescence studies indicated that M2BP is present on the prostasome surface and on sperm, respectively. CONCLUSIONS: M2BP, CD26, PIP, OLFM4, and SgI and SgII are candidate glycoprotein ligands for galectin-3 in prostasomes. Given their overlap in functional significance with prostasomes and galectin-3, the identification of these glycoproteins as galectin-3 ligands in prostasomes lays the groundwork for future studies of prostasomes in reproduction and prostate cancer. PMID- 21031434 TI - Elevated expression of cancer-associated proliferating cell nuclear antigen in high-grade prostatic intraepithelial neoplasia and prostate cancer. AB - BACKGROUND: Proliferating cell nuclear antigen (PCNA) plays an important role in DNA replication and repair. The expression and potential utility of this marker in prostatic neoplasia is uncertain. With the development of this new caPCNA selective antibody, we explored the potential utility of this marker in prostate cancer. METHODS: Using a traditional primary Fab2' rabbit anti-caPCNA antibody HRP conjugated secondary anti-Fab2' antibody format, the expression of the caPCNA was analyzed in prostate tissue from 89 radical prostatectomy specimens. The caPCNA expression was correlated with clinicopathologic characteristics. RESULTS: The fraction of cells staining positively with caPCNA antibody in prostatic adenocarcinoma (mean, 23%) was significantly higher than that in benign prostatic epithelium (mean, 2%; P < 0.001) or high-grade prostatic intraepithelial neoplasia (PIN) (mean, 6%; P < 0.05). Moreover, the intensity of caPCNA expression in prostatic adenocarcinoma (mean, 2.9) was significantly higher than that in benign prostatic tissue (mean, 0.7; P < 0.001) or high-grade PIN (mean, 2.0; P < 0.001). Benign prostatic epithelium showed only minimal or negative reactivity. There was significant correlation between the percentage of caPCNA expression and primary Gleason grade (P = 0.01), and with Gleason score (P = 0.02). Adenocarcinomas with positive vascular invasion had a significantly higher percentage of cells staining with caPCNA antibody (P < 0.0001) and a higher intensity of caPCNA expression (P = 0.04). CONCLUSIONS: Our data indicate that increased expression of the cancer-associated isoform of PCNA is common in prostatic adenocarcinoma and its precursor and may be a useful biomarker. PMID- 21031435 TI - Differential expression of peroxiredoxins in prostate cancer: consistent upregulation of PRDX3 and PRDX4. AB - BACKGROUND: The peroxiredoxins (PRDXs) are emerging as regulators of antioxidant defense, apoptosis, and therapy resistance in cancer. Because their significance in prostate cancer (PCa) is unclear, we investigated their expression and clinical associations in PCa. METHODS: Transcript expression of PRDX1-6 in PCa was evaluated in cancer gene microarray datasets, whereas protein expression was evaluated by immunoblotting in prostate cell lines, and by immunohistochemistry (IHC) in prostate tissue microarrays (TMAs) containing tumor (n = 80) and control (n = 17) tissues. PRDX3 was also analyzed in TMAs containing PCa tissues from African-American and Caucasian patients (n = 150 per group). PRDX expression was correlated with patients' clinicopathologic characteristics. RESULTS: Analysis of PRDX expression in cancer microarray datasets revealed consistent upregulation (tumor vs. normal) of PRDX3 and 4. All PRDXs exhibited elevated protein expression in PCa cell lines, compared with non-tumor cells. IHC revealed significant overexpression of PRDX3 and 4 in PCa, associated with age, increased prostate specific antigen (PSA), tumor stage, or Gleason score. High PRDX3 staining was associated with early age and elevated Gleason score at time of radical prostatectomy in African-American but not in Caucasian patients with PCa. PSA recurrence free survival in patients with low PRDX3 tumor expression was significantly longer in Caucasians compared to African-Americans, but no difference was detected for high expression. CONCLUSIONS: PRDXs exhibit differential expression in prostate tumors, with PRDX3 and 4 consistently upregulated. Their role in PCa development, and their potential as biological determinants of PCa health disparities and novel therapeutic targets, deserve further investigation. PMID- 21031437 TI - Topographical analysis of telomere length and correlation with genomic instability in whole mount prostatectomies. AB - BACKGROUND: Many critical events in prostatic carcinogenesis appear to relate to the emergence of genomic instability. Characteristic genomic abnormalities such as 8p loss, 8q gain, trisomy 7, and PTEN microdeletions may provide selective advantages to increase neoplastic transformation. Evidence suggests that telomere dysfunction is a plausible mechanism for some of these abnormalities on the basis of the break-fusion-bridge cycle that can lead to manifestations of genomic instability. METHODS: In this study, we correlate telomere length measured by quantitative FISH in various prostatic histologies with markers of genomic instability and immunohistochemical measures of proliferation and oxidative stress. RESULTS: We find that telomere shortening is correlated with abnormalities on chromosome 8, but not with trisomy 7 or abnormalities of the PTEN locus. There are associations with C-MYC aberrations in stroma with greater proximity to cancer and a correlation between telomere length in a number of prostatic histologies and the adjacent stroma, suggesting the importance of microenvironmental effects on telomere maintenance in the prostate. This finding was also supported by the finding of the correlation between telomere attrition and the levels of oxidative stress as measured by malondialdehyde staining in HPIN lesions close to cancer. CONCLUSIONS: Telomere attrition in the prostate gland is associated with particular genomic aberrations that contribute to the genomic instability characteristic of prostatic carcinogenesis. Correlations between various histologies and adjacent stroma telomere length suggest it is also may reveal microenvironmental effects within the prostate gland. Oxidative stress may contribute to telomere attrition in HPIN close to cancer. PMID- 21031436 TI - Androgen-induced PSA expression requires not only activation of AR but also endogenous IGF-I or IGF-I/PI3K/Akt signaling in human prostate cancer epithelial cells. AB - BACKGROUND: Prostate cancer (PrCa) risk is positively associated with levels of insulin-like growth factor I (IGF-I) and prostate specific antigen (PSA), both androgen receptor (AR) signaling target genes in PrCa cells. Although activated AR is required for androgen-induction of expression of both genes, effects of the IGF-I signaling pathways on the androgen-induction of PSA have not been studied. METHODS: Human prostate stromal and epithelial cancer cells were treated alone or in coculture with steroid hormone and/or inhibitors. Gene or protein expression was analyzed by real time RT-PCR or Western blotting of lysates, nuclear extracts, or immunoprecipitated products. RESULTS: In PrCa epithelial cells, endogenous IGF-I, significantly induced by R1881, was required for R1881 induction of PSA. Increased IGF-I correlated with accumulation of cytoplasmic dephospho beta-catenin (CPDP beta-catenin), a co-activator of AR signaling. Exogenous IGF-I enhanced R1881-induced PSA and accumulation of CPDP beta-catenin in LAPC-4 cells. Functional depletion of IGF-I or IGF-I receptor diminished PSA induction. Induction of IGF-I reached a plateau while PSA consecutively increased. Inhibiting PI3K abolished R1881-induced Akt phosphorylation, CPDP and nuclear beta-catenin and nuclear association of AR/beta-catenin, consequently abrogating R1881-induced expression of IGF-I and/or PSA. CONCLUSIONS: By integrating androgen, IGF-I and beta-catenin signaling pathways, these data reveal that androgen-induced PSA expression requires activation of AR and endogenous IGF-I or IGF-I/PI3K/Akt signaling, suggesting a positive feedback cycle for increased production of PSA associated with PrCa. PMID- 21031450 TI - Recent progresses on materials for electrophosphorescent organic light-emitting devices. AB - Although organic light-emitting devices have been commercialized as flat panel displays since 1997, only singlet excitons were emitted. Full use of singlet and triplet excitons, electrophosphorescence, has attracted increasing attentions after the premier work made by Forrest, Thompson, and co-workers. In fact, red electrophosphorescent dye has already been used in sub-display of commercial mobile phones since 2003. Highly efficient green phosphorescent dye is now undergoing of commercialization. Very recently, blue phosphorescence approaching the theoretical efficiency has also been achieved, which may overcome the final obstacle against the commercialization of full color display and white light sources from phosphorescent materials. Combining light out-coupling structures with highly efficient phosphors (shown in the table-of-contents image), white emission with an efficiency matching that of fluorescent tubes (90 lm/W) has now been realized. It is possible to tune the color to the true white region by changing to a deep blue emitter and corresponding wide gap host and transporting material for the blue phosphor. In this article, recent progresses in red, green, blue, and white electrophosphorescent materials for OLEDs are reviewed, with special emphasis on blue electrophosphorescent materials. PMID- 21031451 TI - Joint testing of genotype and ancestry association in admixed families. AB - Current genome-wide association studies (GWAS) often involve populations that have experienced recent genetic admixture. Genotype data generated from these studies can be used to test for association directly, as in a non-admixed population. As an alternative, these data can be used to infer chromosomal ancestry, and thus allow for admixture mapping. We quantify the contribution of allele-based and ancestry-based association testing under a family-design, and demonstrate that the two tests can provide non-redundant information. We propose a joint testing procedure, which efficiently integrates the two sources information. The efficiencies of the allele, ancestry and combined tests are compared in the context of a GWAS. We discuss the impact of population history and provide guidelines for future design and analysis of GWAS in admixed populations. PMID- 21031458 TI - TOP or palliative care for lethal foetal condition? PMID- 21031455 TI - Genotype-based association mapping of complex diseases: gene-environment interactions with multiple genetic markers and measurement error in environmental exposures. AB - With the advent of dense single nucleotide polymorphism genotyping, population based association studies have become the major tools for identifying human disease genes and for fine gene mapping of complex traits. We develop a genotype based approach for association analysis of case-control studies of gene environment interactions in the case when environmental factors are measured with error and genotype data are available on multiple genetic markers. To directly use the observed genotype data, we propose two genotype-based models: genotype effect and additive effect models. Our approach offers several advantages. First, the proposed risk functions can directly incorporate the observed genotype data while modeling the linkage disequilibrium information in the regression coefficients, thus eliminating the need to infer haplotype phase. Compared with the haplotype-based approach, an estimating procedure based on the proposed methods can be much simpler and significantly faster. In addition, there is no potential risk due to haplotype phase estimation. Further, by fitting the proposed models, it is possible to analyze the risk alleles/variants of complex diseases, including their dominant or additive effects. To model measurement error, we adopt the pseudo-likelihood method by Lobach et al. [2008]. Performance of the proposed method is examined using simulation experiments. An application of our method is illustrated using a population-based case-control study of association between calcium intake with the risk of colorectal adenoma development. PMID- 21031461 TI - Poly(ADP-ribose) polymerase 1 is involved in glucose toxicity through SIRT1 modulation in HepG2 hepatocytes. AB - Accelerated glucose metabolism leads to oxidative stress and DNA damage in cells; these effects are related to glucose toxicity. The precise mechanisms of glucose toxicity are still unclear. The aim of this work was to investigate the mechanism of poly(ADP-ribose) polymerase 1 (PARP1), which is a DNA repair enzyme activated by high-glucose-induced oxidative stress, and its effect on glucose toxicity in HepG2 hepatocytes. HepG2 cells were cultured under normal (5.5 mM) or high (30 mM) glucose conditions for 4 days. PJ34, which is an inhibitor of PARP1, was used to determine the downstream effects of PARP1 activation. PARP1 activity in 30 mM glucose-treated cells was more than that in 5.5 mM-glucose-treated cells, and the activity correlated with the increase in ROS generation and DNA damage. PJ34 suppressed PARP1 activation and prevented the high-glucose-induced suppression of SIRT1 and AMP-activated protein kinase (AMPK) activity, which was similar to its effect on the restoration of intracellular nicotinamide adenine dinucleotide (NAD) content. Further, the phosphorylation of insulin receptor was attenuated in response to insulin stimulation under high glucose conditions, and PJ34 could reverse this effect. The results of transfection of HepG2 cells with PARP1 small interfering RNA were similar to those obtained by treatment of the cells with PARP1 inhibitor PJ34. These data suggest that high-glucose-induced PARP1 activation might play a role in glucose toxicity by down-regulating SIRT1 and AMPK activity through NAD depletion and resulting in insulin insensitivity. PMID- 21031462 TI - A review on the development of liquid chromatography systems for polyolefins. AB - Polyolefins are the most widely produced synthetic polymer commodity and are found in countless applications ranging from bottles, packaging films to bullet proof jackets, etc. Such widely different applications rely on high variability in the physical properties of polyolefins, which is a result of variations in microstructure, chemical composition and molar mass. Though polyolefins contain only carbon (C) and hydrogen (H) atoms, the microstructures of polyolefins are extremely variable, differing in the nature of the monomers (e.g. ethylene versus propylene), the degree of branching, chemical composition in the case of copolymers and finally their molar masses. Production, research and development of polyolefins require the analysis of polyolefin samples in terms of all these parameters. Development of efficient and robust analytical techniques based on the interactive LC is reviewed. The needed computational/theoretical studies to understand the retention mechanism in the newly developed chromatography systems are discussed. PMID- 21031463 TI - Micron-sized pillars for ion-pair reversed-phase DNA separations. AB - In the present paper, the feasibility to construct micron-sized silicon pillar channels to be used in HPLC is studied. For this, a channel with flow-through pores of 1 MUm and with critical sidewall dimensions below 1 MUm was constructed using advanced deep-UV lithographic equipment. Integrating a 3-nL injection system on the chip directly in front of the separation channel and using elongated distribution structures, a very controlled and high aspect ratio sample definition across the relatively wide separation channel was accomplished. The system was evaluated in isocratic ion-pair RP mode, allowing the separation of a mixture of two components with, respectively, 300 and 400 base pairs in 5 s only. PMID- 21031464 TI - Prevention of complications following pelvic exenteration with the use of mammary implants in the pelvic cavity: Technique and results of 28 cases. AB - BACKGROUND: With the evolution of neo-adjuvant therapy and the introduction of peritonectomy with chemotherapy in surgical practice, pelvic exenteration has taken second place in the treatment of advanced pelvic tumors. This surgery remains the first of choice for the treatment of T4 superior and medium rectal tumors that are not susceptible to neo-adjuvant radiochemotherapy, for uterine tumors and cervical FIGO IV T4, for pelvic recurrence and for T4 bladder tumors. After a pelvic exenteration the pelvic cavity becomes occupied by the intestinal loops, causing an increase in the risk of short and long-term complications such as radiation enteritis in the case of post-operative radiotherapy, occlusions, and enteric fistulas that could be avoided by isolating the small intestine in the pelvic cavity. METHODS: With this aim we positioned a mammary prosthesis (implant) in the cavity of the last 28 cases we treated, and did not observe complications related to the prosthetic implant. RESULTS: No early or delayed complications, such as occlusions or fistulas, were observed. All the patients treated underwent adjuvant radiotherapy with no evidence of radiation enteritis. Ten patients were recanalized with removal of the implant, ultra-low rectal anastomosis was performed in six cases and colo-anal anastomosis was performed in four cases. Eight patients were not recanalized, six distance due to recurrence and two local recurrence. Nine patients are currently in follow-up, disease free between 1 and 12 months. CONCLUSIONS: We retain the encouraging results observed that the use of mammary implants in the pelvic cavity after pelvic exenteration should be part of the cultural patrimony of the surgeon who approaches this type of major radical surgery. PMID- 21031476 TI - In vitro studies with mammalian cell lines and gum arabic-coated magnetic nanoparticles. AB - Iron oxide magnetic nanoparticles (MNPs) were synthesized by the chemical co precipitation method and coated with gum arabic (GA) by physical adsorption and covalent attachment. Cultures of mammalian cell lines (HEK293, CHO and TE671) were grown in the presence of uncoated and GA-coated MNPs. Cellular growth was followed by optical microscopy in order to assess the proportion of cells with particles, alterations in cellular density and the presence of debris. The in vitro assays demonstrated that cells from different origins are affected differently by the presence of the nanoparticles. Also, the methods followed for GA coating of MNPs endow distinct surface characteristics that probably underlie the observed differences when in contact with the cells. In general, the nanoparticles to which the GA was adsorbed had a smaller ability to attach to the cells' surface and to compromise the viability of the cultures. PMID- 21031466 TI - Effects of nozzle type and spray angle on spray deposition in ivy pot plants. AB - BACKGROUND: Fewer plant protection products are now authorised for use in ornamental growings. Frequent spraying with the same product or a suboptimal technique can lead to resistance in pests and diseases. Better application techniques could improve the sustainable use of the plant protection products still available. Spray boom systems--instead of the still predominantly used spray guns--might improve crop protection management in greenhouses considerably. The effect of nozzle type, spray pressure and spray angle on spray deposition and coverage in ivy pot plants was studied, with a focus on crop penetration and spraying the bottom side of the leaves in this dense crop. RESULTS: The experiments showed a significant and important effect of collector position on deposition and coverage in the plant. Although spray deposition and coverage on the bottom side of the leaves are generally low, they could be improved 3.0-4.9 fold using the appropriate application technique. CONCLUSIONS: When using a spray boom in a dense crop, the nozzle choice, spray pressure and spray angle should be well considered. The hollow-cone, the air-inclusion flat-fan and the standard flat-fan nozzle with an inclined spray angle performed best because of the effect of swirling droplets, droplets with a high momentum and droplet direction respectively. PMID- 21031477 TI - Proteolysis activity of IgM antibodies from rheumatoid arthritis patients' sera: evidence of atypical catalytic site. AB - The IgM antibodies from rheumatoid arthritis (RA) patients' sera were screened for peptide hydrolyzing activity. Recovery of structurally intact IgM antibodies (Abs), in a single step, was achieved using a weak anion-exchange methacrylate monolith disk. The IgM Abs from patients' sera hydrolyzed the Pro-Phe-Arg-4 methyl-coumaryl-7-amide (PFR-MCA) substrate appreciably compared to the healthy donors. The apparent K(m) values of IgM Abs from patients' sera were between 0.4 and 0.7 mM. Furthermore, IgM Abs displayed 5 to 10-folds greater proteolysis activity than IgG Abs, recovered from the same pathological serum. The proteolysis activity, as a function, was found to be independent of IgM-RF titer value. Affinity labeling approach targeted at the catalytic site histidine was studied, using a specific irreversible inhibitor, N-alpha-tosyl-L-lysine chloromethyl ketone (TLCK). Despite modification of catalytic His, observation of serine protease like activity suggest presence of an atypical catalytic framework in a few pathological IgM Abs. PMID- 21031478 TI - Warfarin: an environment-dependent switchable molecular probe. AB - The complex nature of the structure of the anticoagulant warfarin is reflected in the diversity of binding modes observed in warfarin-protein recognition systems. A series of theoretical, (1)H-NMR and steady state and time resolved fluorescence spectroscopic studies, have been used to establish correlations between the molecular environment provided by various solvent systems and the relative concentrations of the various members of warfarin's ensemble of isomers. A consequence of these observations is that the judicious choice of solvent system or molecular environment of warfarin allows for manipulation of the position of the equilibrium between isomeric structures such as the hemiacetal and open phenol-keto forms, the latter even possible in a deprotonated form, where in each case unique spectroscopic properties are exhibited by the respective structures. Collectively, warfarin's capacity to adapt its structure as a function of environment in conjunction with the fluorescence behaviours of the various isomers together provide an environment-dependent molecular switch with reporter properties, which allows for the simultaneous detection of warfarin in different states with lifetimes spanning the range < 0.10-5.5 ns. These characteristics are here used to examine warfarin binding domains in a series of materials (solvents, protein, inorganic matrix and synthetic polymer). Moreover, these studies demonstrate the potential for using warfarin, or other switchable analogues thereof, as a tool for studying molecular level characteristics, for example local dielectricity. PMID- 21031484 TI - Cryoprotective mechanism of a small intrinsically disordered dehydrin protein. AB - Dehydration proteins (Dehydrins) are expressed during dehydration stress in plants and are thought to protect plant proteins and membranes from the loss of water during drought and at cold temperatures. Several different dehydrins have been shown to protect lactate dehydrogenase (LDH) from damage from being frozen and thawed. We show here that a 48 residue K2 dehydrin from Vitis riparia protects LDH more effectively than bovine serum albumin, a protein with known cryoprotective function. Light scattering and 8-anilino-1-naphthalene sulfonate fluorescence experiments show that dehydrins prevent aggregation and unfolding of the enzyme. The cryoprotective effects of LDH are reduced by the addition of salt, suggesting that the positively charged K-segments are attracted to a negatively charged surface but this does not result in binding. Overall K2 is an intrinsically disordered protein; nuclear magnetic resonance relaxation experiments indicate that the two-terminal, Lys-rich K-segments show a weak propensity for alpha-helicity and are flexible, and that the central, polar rich phi-segment has no secondary structure preference and is highly flexible. We propose that the phi-segments in dehydrins are important for maintaining the disordered structure so that the protein can act as a molecular shield to prevent partially denatured proteins from interacting with one another, whereas the K segments may help to localize the dehydrin near the enzyme surface. PMID- 21031485 TI - Restrained expression, a method to overproduce toxic membrane proteins by exploiting operator-repressor interactions. AB - A major rate-limiting step in determining structures of membrane proteins is heterologous protein production. Toxicity often associated with rapid overexpression results in reduced biomass along with low yields of target protein. Mitigation of toxic effects was achieved using a method we call "restrained expression," a controlled reduction in the frequency of transcription initiation by exploiting the infrequent transitions of Lac repressor to a free state from its complex with the lac-operator site within a T7lac promoter that occur in the absence of the inducer isopropyl beta-D-1-thiogalactopyranoside. In addition, production of the T7 RNA polymerase that drives transcription of the target is limited using the tightly regulated arabinose promoter in Escherichia coli strain BL21-AI. Using this approach, we can achieve a 200-fold range of green fluorescent protein expression levels. Application to members of a family of ion pumps results in 5- to 25-fold increases in expression over the benchmark BL21(DE3) host strain. A viral ion channel highly toxic to E. coli can also be overexpressed. In comparative analyses, restrained expression outperforms commonly used E. coli expression strategies. The mechanism underlying improved target protein yield arises from minimization of protein aggregation and proteolysis that reduce membrane integrity and cell viability. This study establishes a method to overexpress toxic proteins. PMID- 21031486 TI - The C. elegans B-cell lymphoma 2 (Bcl-2) homolog cell death abnormal 9 (CED-9) associates with and remodels LIPID membranes. AB - Bcl-2 proteins associate with and remodel mitochondria to regulate apoptosis. While the C. elegans Bcl-2 homolog CED-9 constitutively associates with mitochondria, it is unclear whether or not this association reflects an innate ability of CED-9 to directly remodel mitochondrial membranes. To address this question, we have characterized the effects of recombinantly expressed and purified CED-9 on synthetic lipid vesicles. We found that CED-9 associates with anionic lipid vesicles at neutral pH, and that association can occur independently of the C-terminal transmembrane domain. Membrane association changes the environment of CED-9 tryptophans and results in an apparent increase in alpha-helical structure. Upon association, CED-9 alters the permeability of membranes resulting in leakage of encapsulated dyes. Furthermore, this membrane remodeling promotes membrane fusion upon protonation of CED-9. Bypass of this protonation trigger can be achieved by mutating two conserved glutamates (E187K/E190K) or removing the N-terminal 67 residues. Together, these in vitro results suggest that CED-9 retains the amphitropic ability of mammalian Bcl-2 proteins to associate with cellular membranes. We therefore discuss the possibility that CED-9 and other Bcl-2 homologs localize at mitochondria to regulate mitochondrial homeostasis by either modulating mitochondrial membrane permeability or fusion. PMID- 21031487 TI - The crystal structures of the Salmonella type III secretion system tip protein SipD in complex with deoxycholate and chenodeoxycholate. AB - The type III secretion system (T3SS) is a protein injection nanomachinery required for virulence by many human pathogenic bacteria including Salmonella and Shigella. An essential component of the T3SS is the tip protein and the Salmonella SipD and the Shigella IpaD tip proteins interact with bile salts, which serve as environmental sensors for these enteric pathogens. SipD and IpaD have long central coiled coils and their N-terminal regions form alpha-helical hairpins and a short helix alpha3 that pack against the coiled coil. Using AutoDock, others have predicted that the bile salt deoxycholate binds IpaD in a cleft formed by the alpha-helical hairpin and its long central coiled coil. NMR chemical shift mapping, however, indicated that the SipD residues most affected by bile salts are located in a disordered region near helix alpha3. Thus, how bile salts interact with SipD and IpaD is unclear. Here, we report the crystal structures of SipD in complex with the bile salts deoxycholate and chenodeoxycholate. Bile salts bind SipD in a region different from what was predicted for IpaD. In SipD, bile salts bind part of helix alpha3 and the C terminus of the long central coiled coil, towards the C-terminus of the protein. We discuss the biological implication of the differences in how bile salts interact with SipD and IpaD. PMID- 21031492 TI - Prior estimate-based compressed sensing in parallel MRI. AB - Two improved compressed sensing (CS)-based image reconstruction methods for MRI are proposed: prior estimate-based compressed sensing (PECS) and sensitivity encoding-based compressed sensing (SENSECS). PECS allows prior knowledge of the underlying image to be intrinsically incorporated in the image recovery process, extending the use of data sorting as first proposed by Adluru and DiBella (Int J Biomed Imaging 2008: 341648). It does so by rearranging the elements in the underlying image based on the magnitude information gathered from a prior image estimate, so that the underlying image can be recovered in a new form that exhibits a higher level of sparsity. SENSECS is an application of PECS in parallel imaging. In SENSECS, image reconstruction is carried out in two stages: SENSE and PECS, with the SENSE reconstruction being used as a image prior estimate in the following PECS reconstruction. SENSECS bypasses the conflict of sampling pattern design in directly applying CS recovery in multicoil data sets and exploits the complementary characteristics of SENSE-type and CS-type reconstructions, hence achieving better image reconstructions than using SENSE or CS alone. The characteristics of PECS and SENSECS are investigated using experimental data. PMID- 21031496 TI - Nanoporous nickel spheres as highly active catalyst for hydrogen generation from ammonia borane. PMID- 21031497 TI - A cross-linked soft matter polymer electrolyte for rechargeable lithium-ion batteries. PMID- 21031499 TI - Human disease and transcriptional misregulation have strengthened. PMID- 21031501 TI - Binding of the Rett syndrome protein, MeCP2, to methylated and unmethylated DNA and chromatin. AB - Methylated CpG Binding Protein 2 (MeCP2) is a nuclear protein named for its ability to selectively recognize methylated DNA. Much attention has been focused on understanding MeCP2 structure and function in the context of its role in Rett syndrome, a severe neurodevelopmental disorder that afflicts one in 10,000-15,000 girls. Early studies suggested a connection between DNA methylation, MeCP2, and establishment of a repressive chromatin structure at specific gene promoters. However, it is now recognized that MeCP2 can both activate and repress specific genes depending on the context. Likewise, in the cell, MeCP2 is bound to unmethylated DNA and chromatin in addition to methylated DNA. Thus, to understand the molecular basis of MeCP2 functionality, it is necessary to unravel the complex interrelationships between MeCP2 binding to unmethylated and methylated regions of the genome. MeCP2 is unusual and interesting in that it is an intrinsically disordered protein, that is, much of its primary sequence fails to fold into secondary structure and yet is functional. The unique structure of MeCP2 is the subject of the first section of this article. We then discuss recent investigations of the in vitro binding of MeCP2 to unmethylated and methylated DNA, and the potential ramifications of this work for in vivo function. We close by focusing on mechanistic studies indicating that the binding of MeCP2 to chromatin results in compaction into local (secondary) and global (tertiary) higher order structures. MeCP2 also competes with histone H1 for nucleosomal binding sites. The recent finding that MeCP2 is found at near stoichiometric levels with nucleosomes in neuronal cells underscores the multiple modes of engagement of MeCP2 with the genome, which include the cooperative tracking of methylation density. PMID- 21031502 TI - Metabolic functions of AMPK: aspects of structure and of natural mutations in the regulatory gamma subunits. AB - AMP-activated protein kinase, AMPK, is widely accepted as the master regulator of energy levels within the cell. Responding quickly to changing energy demands, AMPK works to restore levels of ATP during times of cellular stress by promoting ATP producing catabolic pathways and inhibiting ATP consuming anabolic ones. As a heterotrimeric protein complex, AMPK's subunits each act in unique and crucial ways to control AMPK function and its localization within the cell. Research in the last decade has identified and begun to characterize the impact of naturally occurring mutations in the gamma regulatory subunits. Mutations in the gamma2 subunit have implications for cardiac function and disease, while the R225W mutation in the gamma3 subunit have implications for skeletal muscle fuel metabolism and resistance to fatigue. Research focused on structure-function aspects of AMPK regulatory subunits will lead to a better understanding of the roles of AMPK in health and disease. PMID- 21031504 TI - Acute abdominal pain: is there a potential role for MRI in the setting of the emergency department in a patient with renal calculi? AB - Acute flank pain is a frequent clinical presentation encountered in emergency departments, and a work-up for obstructive urolithiasis in this setting is a common indication for computed tomography (CT). However, imaging alternatives to CT for the evaluation of renal colic are warranted in some clinical situations, such as younger patients, pregnancy, patients that have undergone multiple prior CT exams and also patients with vague clinical presentations. MRI, although relatively insensitive for the direct detection of urinary calculi, has the ability to detect the secondary effects of obstructive urolithiasis. Using rapid, single shot T2-weighted sequences without and with fat saturation provides an abdominopelvic MR examination that can detect the sequelae of clinically active stone disease, in addition to alternate inflammatory processes that may mimic the symptoms of renal colic. In addition, MR nephro-urography (MRNU) has the ability to provide quantitative analysis of renal function that has the potential to direct clinical management in the setting of obstructing calculi. This review describes the potential utility and limitations of MRI in the emergency setting for diagnosing causes of flank pain and renal colic, particularly in patients with unusual presentations or when an alternative to CT may be warranted. PMID- 21031505 TI - Real-time diffusion-perfusion mismatch analysis in acute stroke. AB - Diffusion-perfusion mismatch can be used to identify acute stroke patients that could benefit from reperfusion therapies. Early assessment of the mismatch facilitates necessary diagnosis and treatment decisions in acute stroke. We developed the RApid processing of PerfusIon and Diffusion (RAPID) for unsupervised, fully automated processing of perfusion and diffusion data for the purpose of expedited routine clinical assessment. The RAPID system computes quantitative perfusion maps (cerebral blood volume, CBV; cerebral blood flow, CBF; mean transit time, MTT; and the time until the residue function reaches its peak, T(max)) using deconvolution of tissue and arterial signals. Diffusion weighted imaging/perfusion-weighted imaging (DWI/PWI) mismatch is automatically determined using infarct core segmentation of ADC maps and perfusion deficits segmented from T(max) maps. The performance of RAPID was evaluated on 63 acute stroke cases, in which diffusion and perfusion lesion volumes were outlined by both a human reader and the RAPID system. The correlation of outlined lesion volumes obtained from both methods was r(2) = 0.99 for DWI and r(2) = 0.96 for PWI. For mismatch identification, RAPID showed 100% sensitivity and 91% specificity. The mismatch information is made available on the hospital's PACS within 5-7 min. Results indicate that the automated system is sufficiently accurate and fast enough to be used for routine care as well as in clinical trials. PMID- 21031506 TI - Combined use of neuroradiology and 1H-MR spectroscopy may provide an intervention limiting diagnosis of glioblastoma multiforme. AB - PURPOSE: To evaluate the accuracy of (1)H-MR spectroscopy ((1)H-MRS) as an intervention limiting diagnostic tool for glioblastoma multiforme. GBM is the most common and aggressive primary brain tumor, with mean survival under a year. Oncological practice currently requires histopathological diagnosis before radiotherapy. MATERIALS AND METHODS: Eighty-nine patients had clinical computed tomography (CT) and MR imaging and 1.5T SV SE (1)H-MRS with PRESS localization for neuroradiological diagnosis and tumor classification with spectroscopic and automated pattern recognition analysis (TE 30 ms, TR 2000 ms, spectral width 2500 Hz and 2048 data points, 128-256 signal averages were acquired, depending on voxel size (8 cm(3) to 4 cm(3)). Eighteen patients from a cohort of 89 underwent stereotactic biopsy. RESULTS: The 18 stereotactic biopsies revealed 14 GBM, 2 grade II astrocytomas, 1 lymphoma, and 1 anaplastic astrocytoma. All 14 biopsied GBMs were diagnosed as GBM by a protocol combining an individual radiologist and an automated spectral pattern recognition program. CONCLUSION: In patients undergoing stereotactic biopsy combined neuroradiological and spectroscopic evaluation diagnoses GBM with accuracy that could replace the need for biopsy. We do not advocate the replacement of biopsy in all patients; instead our data suggest a specific intervention limiting role for the use of (1)H-MRS in brain tumor diagnosis. PMID- 21031507 TI - Lower brain glutamate is associated with cognitive deficits in HIV patients: a new mechanism for HIV-associated neurocognitive disorder. AB - PURPOSE: To determine whether subjects with human immunodeficiency virus (HIV) associated neurocognitive disorder (HAND) show altered concentrations of brain glutamate (GLU), and whether lower GLU levels correlate with cognitive deficits. MATERIALS AND METHODS: GLU concentrations were measured in the basal ganglia, frontal gray and white matter, and parietal gray matter of 45 HIV-positive and 46 age-and-education-matched HIV-negative subjects using echo-time averaged proton magnetic resonance spectroscopy ((1)H MRS). RESULTS: Compared to controls, HIV subjects with cognitive deficits had lower GLU in the parietal gray matter, while those without cognitive deficits tended to show higher basal ganglia GLU. Lower parietal and frontal gray matter GLU were associated with a greater number of nucleoside reverse transcriptase inhibitors, and were predictive of poorer cognitive performance. Correlations between GLU and cognitive performance, but not the other findings, remained significant after correction for multiple comparisons. CONCLUSION: Parietal gray matter GLU is lower in HIV subjects with cognitive deficits. This reduction might result from reduced astrocytic reuptake of GLU, secondary excitotoxicity, and mitochondrial toxicity from antiretroviral treatments. The glutamatergic system may play an important role in the pathophysiology of HAND, and brain GLU on (1)H MRS may provide an early surrogate marker for monitoring disease severity and treatment effects. PMID- 21031509 TI - MRI of the neck at 3 Tesla using the periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) (BLADE) sequence compared with T2 weighted fast spin-echo sequence. AB - PURPOSE: To evaluate motion artifacts, tissue contrasts, and lesion detectability in the neck with the periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) (BLADE) technique. MATERIALS AND METHODS: A total of 46 patients referred for MRI of the neck were included in a comparison of T2-weighted BLADE (T2W-BLADE) sequence and T2W fast spin-echo (T2W-FSE) sequence. All examinations were performed at 3T using the same parameters. Two observers evaluated unlabelled images for motion artifacts, the preferred image quality, and lesion detectability. Region of interest (ROI)-based quantitative measurements were performed to assess tissue contrasts. The frequency of occurrence of the different assessed artifacts and the lesion detectability was tested using McNemar's test. Tissue contrasts were compared using the Wilcoxon paired test. Reader agreement was assessed using kappa test. RESULTS: T2W-BLADE showed less ghosting and pulsation artifacts than T2W-FSE (P < 0.01). T2W-BLADE images were rated as better than or equal to T2W-FSE images in majority cases (93.5%; kappa = 0.64). There was not significant difference in tissue contrasts between T2W-BLADE and T2W-FSE. A total of 32 lesions were present in 32 patients and equally well seen on T2W-BLADE and T2W-FSE. CONCLUSION: T2W-BLADE can reduce motion artifacts and provide tissue contrasts and lesion detectability equivalent to T2W-FSE. PMID- 21031508 TI - Effects of formalin fixation on magnetic resonance indices in multiple sclerosis cortical gray matter. AB - PURPOSE: To investigate changes in magnetic resonance imaging (MRI) indices following formalin fixation of postmortem multiple sclerosis (MS) cortical gray matter (CGM). Postmortem MS brain is being used to establish pathological correlates of changes detected using MRI, with recent emphasis on CGM. Fixation induces tissue alterations that may confound inference of in vivo observations from MRI/histology correlation studies. MATERIALS AND METHODS: T(2)-weighted scans were obtained alongside quantitative T(1), magnetization transfer ratio (MTR), and macromolecular proton fraction (f(B)) measurements before and after formalin fixation of 15 postmortem brain samples. Type and size of CGM lesions (CGML) was identified on sections immunostained for myelin basic protein. RESULTS: MRI indices obtained in unfixed MS CGM were similar to values obtained in subjects with MS in vivo. Fixation led to reduction in T(1) (617 msec [standard deviation = 114] vs. 1156 msec [216]) and MTR (24.1 [3.3] percent units [pu] vs. 29.1 [2.5] pu) and increase in f(B) (5.4 [0.7] pu vs. 3.2 [2.3] pu) (all P < 0.01). The proportion of CGM affected by demyelination did not alter the MRI data. CONCLUSION: MRI indices in the CGM are significantly altered following tissue fixation. PMID- 21031510 TI - Feasibility and precision of cerebral blood flow and cerebrovascular reactivity MRI measurements using a computer-controlled gas delivery system in an anesthetised juvenile animal model. AB - PURPOSE: To demonstrate the feasibility and repeatability of cerebrovascular reactivity (CVR) imaging using a controlled CO(2) challenge in mechanically ventilated juvenile pigs. MATERIALS AND METHODS: Precise end-tidal partial pressure CO(2) (PETCO(2)) control was achieved via a computer-controlled model driven prospective end-tidal targeting (MPET) system integrated with mechanical ventilation using a custom-built secondary breathing circuit. Test-retest blood oxygen level dependent (BOLD) CVR images were collected in nine juvenile pigs by quantifying the BOLD response to iso-oxic square-wave PETCO(2) changes. For comparison, test-retest baseline arterial spin labeling (ASL) cerebral blood flow (CBF) images were collected. Repeatability was quantified using the intra-class correlation coefficient (ICC) and coefficient of variation (CV). RESULTS: The repeatability of the PETCO(2) (CV < 2%) step changes resulted in BOLD CVR ICC > 0.94 and CV < 6% for cortical brain regions, which was similar to ASL CBF repeatability (ICC > 0.96 and CV < 4%). CONCLUSION: This study demonstrates the feasibility and precision of CVR imaging with an MPET CO(2) challenge in mechanically ventilated subjects using an animal model. Translation of this method into clinical imaging protocols may enable CVR imaging in young children with cerebrovascular disease who require general anesthesia. PMID- 21031511 TI - In vivo MR imaging tracking of transplanted mesenchymal stem cells in a rabbit model of acute peripheral nerve traction injury. AB - PURPOSE: To investigate in vivo MRI tracking mesenchymal stem cells (MSCs) in peripheral nerve injures using a clinically available paramagnetic contrast agent (Gd-DTPA) and commercially available rhodamine-incorporated transfection reagents (PEI-FluoR). MATERIALS AND METHODS: After bone marrow MSCs were labeled with Gd DTPA and PEI-FluoR complex, the labeling efficacy and longevity of Gd-DTPA maintenance were measured and cell viability, proliferation, and apoptosis were assessed. Thirty-six rabbits with acute sciatic nerve traction injury randomly received 1 * 10(6) labeled (n = 12) or unlabeled MSCs (n = 12) or vehicle alone injection. The distribution and migration of implanted cells was followed by MRI and correlated with histology. The relative signal intensity (RSL) of the grafts was measured. RESULTS: The labeling efficiency was 76 +/- 4.7% and the labeling procedure did not influence cell viability, proliferation, and apoptosis. A persistent higher RSL in grafts was found in the labeled group compared with the unlabeled and vehicle groups until 10 days after transplantation (P < 0.05). The distribution and migration of labeled cells could be tracked by MRI until 10 days after transplantation. Transplanted MSCs were not found to transdifferentiate into Schwann-like cells within 14-day follow-up. CONCLUSION: Labeling MSCs with the dual agents may enable cellular MRI of the engraftment in the experimental peripheral nerve injury. PMID- 21031512 TI - Improved aortic pulse wave velocity assessment from multislice two-directional in plane velocity-encoded magnetic resonance imaging. AB - PURPOSE: To evaluate the accuracy and reproducibility of aortic pulse wave velocity (PWV) assessment by in-plane velocity-encoded magnetic resonance imaging (MRI). MATERIALS AND METHODS: In 14 patients selected for cardiac catheterization on suspicion of coronary artery disease and 15 healthy volunteers, PWV was assessed with multislice two-directional in-plane velocity-encoded MRI (PWV(i.p.)) and compared with conventionally assessed PWV from multisite one directional through-plane velocity-encoded MRI (PWV(t.p.)). In patients, PWV was also obtained from intraarterially acquired pressure-time curves (PWV(pressure)), which is considered the gold standard reference method. In volunteers, PWV(i.p.) and PWV(t.p.) were obtained in duplicate in the same examination to test reproducibility. RESULTS: In patients, PWV(i.p.) showed stronger correlation and similar variation with PWV(pressure) than PWV(t.p.) (Pearson correlation r = 0.75 vs. r = 0.58, and coefficient of variation [COV] = 10% vs. COV = 12%, respectively). In volunteers, repeated PWV(i.p.) assessment showed stronger correlation and less variation than repeated PWV(t.p.) (proximal aorta: r = 0.97 and COV = 10% vs. r = 0.69 and COV = 17%; distal aorta: r = 0.94 and COV = 12% vs. r = 0.90 and COV = 16%; total aorta: r = 0.97 and COV = 7% vs. r = 0.90 and COV = 13%). CONCLUSION: PWV(i.p.) is an improvement over conventional PWV(t.p.) by showing higher agreement as compared to the gold standard (PWV(pressure)) and higher reproducibility for repeated MRI assessment. PMID- 21031513 TI - Myocardial T2* is not affected by ageing, myocardial fibrosis, or impaired left ventricular function. AB - PURPOSE: To evaluate the influence of alterations in myocardial structure and function from increasing age, myocardial fibrosis, or impaired left ventricular function on myocardial T2*. MATERIALS AND METHODS: Myocardial T2* was measured in 126 subjects without cardiac iron loading, of whom 63 were normals of varying ages, 39 were patients with impaired left ventricular function from various nonsiderotic cardiac causes, and 24 were patients with chronic myocardial infarction affecting the interventricular septum (where myocardial T2* measurements are normally made). RESULTS: The median (Q1, Q3) of myocardial T2* in the normals was 36.3 ms (31.6, 45.4). There was no significant correlation between myocardial T2* and age (R(2) = 0.04; P = 0.11). In the patients with impaired left ventricular function, the median myocardial T2* was 35.5 ms (31, 42.2) (P = 0.34 versus normals). There was no significant correlation between ejection fraction and T2* in patients with left ventricular impairment (R(2) = 0.03; P = 0.33). In the patients with septal infarction, the median septal myocardial T2* was 35.4 ms (32.7, 43) (P = 0.81 vs normals). CONCLUSION: There was no significant change in myocardial T2* associated with any alterations of myocardial structure and function occurring with increasing age, impairment of left ventricular function or septal fibrosis from chronic myocardial infarction. These results indicate that myocardial T2* measurements are robust to these potential confounding parameters. PMID- 21031514 TI - Comparison of magnetic resonance imaging with transthoracic echocardiography in the diagnosis of ventricular septal defect-associated coronary cusp prolapse. AB - PURPOSE: To compare magnetic resonance imaging (MRI) with transthoracic echocardiography (TTE) in the diagnosis of coronary cusp prolapse (CCP) as a complication of ventricular septal defect (VSD). MATERIALS AND METHODS: Twenty three patients (10 males, 13 females, mean age 9 years) with clinically suspected CCP were included in a retrospective study. Long and short axis cine images and electrocardiogram (ECG)-gated axial T1-weighted image MRI images were evaluated for deformity and protrusion of right and noncoronary cusps. We compared MRI and TTE results. We compared the agreement between MRI and TTE in outlet VSD and membranous VSD. RESULTS: On MRI, 19 patients had right coronary cusp prolapse (RCCP), three had noncoronary cusp prolapse (NCCP), and one patient had RCCP and NCCP on MRI. Twenty-two patients had RCCP on TTE and none had NCCP. Seventeen patients had outlet defects and six patients had a membranous defect at operation. All patients with an outlet VSD had RCCP on both MRI and TTE. The agreement between MRI and TTE in outlet VSD was better than in membranous VSD. CONCLUSION: MRI results corresponded with TTE results in patients with outlet VSDs, but discordant results were observed in patients with membranous VSDs. PMID- 21031515 TI - Distribution of cardiac iron measured by magnetic resonance imaging (MRI)-R*2. AB - PURPOSE: To assess regional iron distribution by magnetic resonance imaging (MRI) R(2)* within the heart of patients with beta-thalassemia major (TM) and other iron overload diseases. MATERIALS AND METHODS: Breathhold electrocardiogram (ECG) gated MRI (1.5 T) of the heart was used for the measurement of transverse relaxation rates R(2)* in 32 patients (11-79 years). In a mid-papillary short axis slice divided into septal, anterior, lateral, and posterior quadrants, R(2)* was analyzed from region of interest (ROI)-based signal intensities from 12 echo times (TE = 1.3-26 msec). Typical boundary effects were evaluated in detail. RESULTS: The segmentation of the cardiac wall resulted in highly significant correlations of R(2)* between septal and all other quadrants. In the patient group with R(2)* < 50 s(-1) (normal), all quadrants show higher normalized median rates (126%-174%) than the septum (P < 10(-4)), while this was relatively smaller in the group with septal R(2)* > 50 s(-1). Typical boundary effects on segmental R(2)* from blood, lung tissue, epicardial fat, and hepatic iron could not be easily separated from segmental iron distribution. CONCLUSION: The measurement of MRI-R2* in the interventricular septum is the least affected method by boundary effects to detect patients with iron overload at risk of developing heart failure. PMID- 21031516 TI - 4D time-resolved magnetic resonance angiography for noninvasive assessment of pulmonary arteriovenous malformations patency. AB - PURPOSE: To assess the capability of four-dimensional (4D) time-resolved magnetic resonance angiography (MRA) to assess pulmonary arteriovenous malformations (PAVMs) patency by analyzing pulmonary arterial and venous enhancement kinetics. MATERIALS AND METHODS: Seven patients with eight documented patent PAVMs underwent a 4D-MRA with keyhole and viewsharing compression at 3T with the following parameters: spatial resolution 0.87 * 0.87 * 1.4 mm(3); field of view 500 * 350 * 238 mm(3); dynamic scan time (temporal resolution) 1.2 seconds; total acquisition time 18.1 seconds for six dynamic datasets (6 * 1.2 sec + reference scan: 10.9 sec). All images were reviewed by two experienced radiologists. Image quality was rated on a qualitative 5-point scale (1: not assessable to 5: excellent). Signal value was measured on cross-sectional planes for the afferent arteries and efferent veins of the PAVM, and for normal reference healthy arteries and veins. The difference in time to peak for each coupled artery/vein (dTTPav) was calculated and compared with a Mann-Whitney test between PAVMs and reference vessels. RESULTS: Mean image quality was 3.2 +/- 0.9. dTTPav was significantly smaller in PAVMs (0.15 +/- 0.76 sec) than in reference vessels (3.75 +/- 1.62 sec), P < 0.001. CONCLUSION: 4D-MRA is a promising tool for noninvasive assessment of PAVM patency. PMID- 21031517 TI - Peripheral hyperintense pattern on T2-weighted magnetic resonance imaging (MRI) in breast carcinoma: correlation with early peripheral enhancement on dynamic MRI and histopathologic findings. AB - PURPOSE: To investigate the correlation between the peripheral hyperintense pattern of breast carcinoma on T2-weighted images (T2WI) and the early peripheral enhancement (EPE) on dynamic magnetic resonance imaging (MRI) and to examine the histological characteristics involved in the causes thereof. MATERIALS AND METHODS: The signal intensity of 131 breast carcinomas of common type on T2WI was classified into four types and the correlations between the signal intensity and the histopathological subtypes were evaluated. We investigated correlation with the peripheral hyperintense pattern on a T2WI and other findings on MR images including EPE. In addition, we also investigated the histopathological characteristics in the lesions with a peripheral hyperintense pattern. RESULTS: The signal intensities of the lesions on T2WI demonstrated hyperintensity, isointensity, hypointensity, and a peripheral hyperintense pattern in 26 (20%), 66 (50%), 19 (15%), and 20 (15%) lesions, respectively. A peripheral hyperintense pattern correlated with the appearance of EPE (P < 0.0001) and the degree of central fibrosis (P < 0.0001). CONCLUSION: A peripheral hyperintense pattern on T2WI is a characteristic finding observed in breast carcinomas and correlated with the appearance of EPE. The appearance of a peripheral hyperintense pattern was affected by various histopathological features in the same manner as that observed for the formation of EPE. PMID- 21031518 TI - Association between serial dynamic contrast-enhanced MRI and dynamic 18F-FDG PET measures in patients undergoing neoadjuvant chemotherapy for locally advanced breast cancer. AB - PURPOSE: To investigate the relationship between changes in vascularity and metabolic activity measured by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and dynamic (18)F-FDG-positron emission tomography (PET) in breast tumors undergoing neoadjuvant chemotherapy. MATERIALS AND METHODS: PET and MRI examinations were performed in 14 patients with locally advanced breast cancer (LABC) before and after chemotherapy. Dynamic (18)F-FDG PET measures included (18)F-FDG transport rate constant from blood to tissue (K(1)) and metabolism flux constant (Ki). DCE-MRI measures included initial peak enhancement (PE), signal enhancement ratio (SER), and tumor volume. Spearman rank-order correlations were assessed between changes in PET and MRI parameters, and measures were compared between patients with and without pathologic complete response (pCR) by Mann-Whitney U-test. RESULTS: Changes in glucose delivery (PET K(1)) were closely correlated with changes in tumor vascularity as reflected by DCE-MRI SER (r = 0.83, P < 0.001). Metabolic changes in PET Ki showed moderate correlations with vascularity changes as reflected by SER (r = 0.71) and PE (r = 0.76), and correlated closely with MRI tumor volume (r = 0.79, P < 0.001). Decreases in K(1), Ki, SER, and PE were greater for patients with pCR compared to those with residual disease (P < 0.05). CONCLUSION: Dynamic (18)F-FDG PET and DCE MRI tumor measures of tumor metabolism, vascularity, and volume were well correlated for assessing LABC response to neoadjuvant chemotherapy and significantly discriminated pathologic complete responders. Further work is necessary to assess the value of combined PET and MRI for evaluating tumor pharmacodynamics in response to novel therapy. PMID- 21031519 TI - Diagnosis of colorectal hepatic metastases: Contrast-enhanced ultrasonography versus contrast-enhanced computed tomography versus superparamagnetic iron oxide enhanced magnetic resonance imaging with diffusion-weighted imaging. AB - PURPOSE: To compare the diagnostic accuracy of contrast-enhanced ultrasonography (CE-US), contrast-enhanced CT (CE-CT), and superparamagnetic iron oxide-enhanced MRI (SPIO-MRI) with diffusion-weighted imaging (DWI) in the evaluation of colorectal hepatic metastases. MATERIALS AND METHODS: Thirty-six patients with colorectal cancers were prospectively enrolled and retrospectively evaluated. Of the 86 metastases identified, 16 were confirmed histologically and the remaining 70 were confirmed by follow-up imaging. CE-CT and SPIO-MRI + DWI were independently evaluated by two readers, whereas CE-US was evaluated by consensus reading of two different readers. Area under receiver operating characteristic curve (A(z)), sensitivities, and positive predictive values (PPVs) were calculated and compared. RESULTS: For both readers, SPIO-MRI+DWI had significantly greater A(z) (0.879 and 0.904) and sensitivity (78% and 87%) for all lesions compared with CE-CT (0.779 and 0.793; 59% and 59%) and CE-US (0.811; 69%), and significantly greater A(z) (0.783 and 0.837) and sensitivity (56% and 73%) for lesions <=1 cm compared with CE-CT (0.562 and 0.601; 20% and 22%) and CE US (0.66; 37%). For lesions >1 cm, there was no significant difference in A(z), sensitivity and PPV between all the image sets. CONCLUSION: SPIO-MRI with DWI was the most reliable modality for evaluation of liver metastases particularly for lesions <=1 cm. PMID- 21031520 TI - Diffusion tensor imaging of liver fibrosis in an experimental model. AB - PURPOSE: To characterize changes in diffusion properties of liver using diffusion tensor imaging (DTI) in an experimental model of liver fibrosis. MATERIALS AND METHODS: Liver fibrosis was induced in Sprague-Dawley rats (n = 12) by repetitive dosing of carbon tetrachloride (CCl(4)). The animals were examined with a respiratory-gated single-shot spin-echo echo-planar DTI protocol at 7 T before, 2 weeks after, and 4 weeks after CCl(4) insult. Apparent diffusion coefficient (ADC), directional diffusivities (ADC(//) and ADC(?)), and fractional anisotropy (FA) were measured. Liver histology was performed with hematoxylin-eosin staining and Masson's trichrome staining. RESULTS: Significant decrease (P < 0.01) in ADC was found at 2 weeks (0.86 +/- 0.09 * 10(-3) mm(2)/s) and 4 weeks (0.74 +/- 0.09 * 10(-3) mm(2)/s) following CCl(4) insult, as compared with that before insult (0.97 +/- 0.08 * 10(-3) mm(2)/s). Meanwhile, FA at 2 weeks (0.18 +/- 0.03) after CCl(4) insult was significantly lower (P < 0.01) than that before insult (0.26 +/ 0.05), and subsequently normalized at 4 weeks (0.26 +/- 0.07) after the insult. Histology showed collagen deposition, presence of intracellular fat vacuoles, and cell necrosis/apoptosis in livers with CCl(4) insult. CONCLUSION: DTI detected the progressive changes in water diffusivities and diffusion anisotropy of liver tissue in this liver fibrosis model. ADC and FA are potentially valuable in detecting liver fibrosis at early stages and monitoring its progression. Future human studies are warranted to further verify the applicability of DTI in characterizing liver fibrosis and to determine its role in clinical settings. PMID- 21031522 TI - Screening for embryonic loss during in utero development of mice with a human 1.5 Tesla clinical MRI scanner. AB - PURPOSE: To establish in utero MRI-scanning of mouse implantation sites in a 1.5 Tesla whole-body human clinical scanner for evaluation of impaired implantation, placental or developmental defects due to genetic alterations. MATERIALS AND METHODS: Pregnant C57Bl/6 wild-type and Cx31-deficient mice revealing placental defects were analyzed in utero using a 1.5 Tesla whole-body clinical scanner in combination with a 3-cm-diameter single loop (slice thickness: 1.2 mm). Imaging of implantation sites was evaluated from 6.5-13.5 dpc and amount of implantation sites and in vivo development was analyzed during the critical phase of placentation from 10.5-13.5 dpc. RESULTS: This method provided high resolution in plane images permitting confident identification of all implantation sites from 6.5 dpc onward. A loss of 60% of Cx31-deficient embryos was demonstrated compared with controls. Repeated anesthesia as well as imaging protocols produced no gross malformations in the surviving mice. CONCLUSION: Using a human clinical MRI scanner high resolution imaging of the entire uterus of the mice and all the embryos inside could be performed. This method is well suited to noninvasively monitor and quantify embryo implantation and to follow this dynamic process in vivo without compromising pregnancy progression and embryonic development. PMID- 21031521 TI - Semi-automatic deformable registration of prostate MR images to pathological slices. AB - PURPOSE: To present a semi-automatic deformable registration algorithm for co registering T2-weighted (T2w) images of the prostate with whole-mount pathological sections of prostatectomy specimens. MATERIALS AND METHODS: Twenty four patients underwent 1.5 Tesla (T) endorectal MR imaging before radical prostatectomy with whole-mount step-section pathologic analysis of surgical specimens. For each patient, the T2w imaging containing the largest area of tumor was manually matched with the corresponding pathologic slice. The prostate was co registered using a free-form deformation (FFD) algorithm based on B-splines. Registration quality was assessed through differences between prostate diameters measured in right-left (RL) and anteroposterior (AP) directions on T2w images and pathologic slices and calculation of the Dice similarity coefficient, D, for the whole prostate (WP), the peripheral zone (PZ) and the transition zone (TZ). RESULTS: The mean differences in diameters measured on pathology and MR imaging in the RL direction and the AP direction were 0.49 cm and -0.63 cm, respectively, before registration and 0.10 cm and -0.11 cm, respectively, after registration. The mean D values for the WP, PZ and TZ, were 0.76, 0.65, and 0.77, respectively, before registration and increased to 0.91, 0.76, and 0.85, respectively, after registration. The improvements in D were significant for all three tissues (P < 0.001 for all). CONCLUSION: The proposed semi-automatic method enabled successful co-registration of anatomical prostate MR images to pathologic slices. PMID- 21031523 TI - Prospective comparison of image quality and diagnostic accuracy of 0.5 molar gadobenate dimeglumine and 1.0 molar gadobutrol in contrast-enhanced run-off magnetic resonance angiography of the lower extremities. AB - PURPOSE: To compare image quality and diagnostic accuracy of 0.5 molar gadobenate dimeglumine and 1.0 molar gadobutrol in contrast-enhanced (CE) magnetic resonance angiography (MRA) of the lower extremities interindividually. MATERIALS AND METHODS: The study was approved by our Institutional Review Board. Written informed consent was obtained from all patients before enrollment in the study. We prospectively included 74 patients (21 women, 53 men; mean age +/- SD: 67.9 +/ 11.0 years) with suspected peripheral occlusive vascular disease. All patients underwent a contrast-enhanced MRA of both lower extremities with either 0.1 mL/kg body weight gadobutrol or gadobenate dimeglumine. Image quality, stenosis grade, and artifacts were assessed by two blinded, independent investigators. Signal intensity (SI), signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were measured by a third investigator. Contrast agent groups were compared to each other using a two-sided Student's t-test. RESULTS: The results did not show significant differences for SI, SNR, or CNR. Both investigators were in significant accordance (P < 0.05) with regard to stenosis detection. CONCLUSION: We conclude that application of standard clinical doses (0.1 mL/kg body weight) of both contrast agents provides similar diagnostic results and gadolinium dose could be reduced by the application of a single dose of gadobenate dimeglumine for CE run-off MRA. PMID- 21031525 TI - Optimization of high-resolution USPIO magnetic resonance imaging at 4.7 T using novel phantom with minimal structural interference. AB - PURPOSE: To characterize the effect of ultrasmall superparamagnetic iron oxides (USPIOs) on magnetic resonance imaging (MRI) signal at 4.7 T, and to find the highest sensitivity pulse sequence for high-resolution USPIO MRI. MATERIALS AND METHODS: A novel phantom was constructed for optimization of sequence parameters for neuroradiological MR applications, and a wide range of dilutions of the USPIO ferumoxtran-10 was imaged using T(2)/T(1)-, T(1)-, T(2)-, T* (2)-, and PD weighted sequences. The effect of varying sequence parameters was investigated using phantom measurements and simulations. RESULTS: The relaxivities r(1), r(2), and r*(2) of ferumoxtran-10 at 4.7 T (21 degrees C) were 5.1, 82.2, and 148.4 mmol(-1) L s(-1), respectively. Gradient echo sequences produced superior susceptibility artifacts at high concentrations; susceptibility artifacts were seen down to a concentration of 137 nmol Fe/mL. A concentration of 17.5 MUmol Fe/mL caused a signal void independently of sequence and parameters, and at concentrations <=273 nmol Fe/mL no signal void was caused. Signal enhancement on T(1)-weighted imaging was seen only at concentrations 137-547 nmol Fe/mL. For the same effective echo time T(2)-weighted rapid acquisition with relaxation enhancement (RARE) yielded significantly higher contrast-to-noise ratio with RARE factor 16 than with RARE factor 8. CONCLUSION: At nanomolar concentrations of USPIO, steady-state free precession offers an alternative to T(2)- and T*(2) weighted sequences. Optimum parameters depend highly on USPIO concentration. PMID- 21031524 TI - Combined off-resonance imaging and T2 relaxation in the rotating frame for positive contrast MR imaging of infection in a murine burn model. AB - PURPOSE: To develop novel magnetic resonance (MR) imaging methods to monitor accumulation of macrophages in inflammation and infection. Positive-contrast MR imaging provides an alternative to negative-contrast MRI, exploiting the chemical shift induced by ultra-small superparamagnetic iron-oxide (USPIO) nanoparticles to nearby water molecules. We introduce a novel combination of off-resonance (ORI) positive-contrast MRI and T(2rho) relaxation in the rotating frame (ORI T(2rho)) for positive-contrast MR imaging of USPIO. MATERIALS AND METHODS: We tested ORI-T(2rho) in phantoms and imaged in vivo the accumulation of USPIO labeled macrophages at the infection site in a mouse model of burn trauma and infection with Pseudomonas aeruginosa (PA). PA infection is clinically important. The USPIO nanoparticles were injected directly in the animals in solution, and macrophage labeling occurred in vivo in the animal model. RESULTS: We observed a significant difference between ORI-T(2rho) and ORI, which leads us to suggest that ORI-T(2rho) is more sensitive in detecting USPIO signal. To this end, the ORI-T(2rho) positive contrast method may prove to be of higher utility in future research. CONCLUSION: Our results may have direct implications in the longitudinal monitoring of infection, and open perspectives for testing novel anti-infective compounds. PMID- 21031526 TI - Fast algorithm for calculation of inhomogeneity gradient in magnetic resonance imaging data. AB - PURPOSE: To develop and implement a new approach for correcting the intensity inhomogeneity in magnetic resonance imaging (MRI) data. MATERIALS AND METHODS: The algorithm is based on the assumption that intensity inhomogeneity in MR data is multiplicative and smoothly varying. Using a statistically stable method, the algorithm first calculates the partial derivative of the inhomogeneity gradient across the data. The algorithm then solves for the gradient field and fits it to a parametric surface. It was tested on both simulated and real human and animal MRI data. RESULTS: The algorithm is shown to restore the homogeneity in all images that were tested. On real human brain images the algorithm demonstrated superior or comparable performance relative to some of the commonly used intensity inhomogeneity correction methods such as SPM, BrainSuite, and N3. CONCLUSION: The proposed algorithm provides an alternative method for correcting the intensity inhomogeneity in MR images. It is shown to be fast and its performance is superior or comparable to algorithms described in the published literature. Due to its generality, this algorithm is applicable to MR images of both humans and animals. PMID- 21031527 TI - Local SAR reduction in parallel excitation based on channel-dependent Tikhonov parameters. AB - PURPOSE: To reduce the local specific absorption rate (SAR) obtained with tailored pulses using parallel transmission while obtaining homogenous flip angle distributions. MATERIALS AND METHODS: Finite-element simulations on a human head model were performed to obtain the individual magnetic and electric field maps for each channel of a parallel transmit array. From those maps, SAR calculations were carried out for "spoke" pulses designed to homogenize the flip angle in an axial slice of a human brain at 7 T. Based on the assumption that the coil element nearest to the maximum local energy deposition is the dominant contributor to the corresponding hot spot, a set of channel-dependent Tikhonov parameters is optimized. Resulting SAR distributions are compared to the ones obtained when using standard pulse design approaches based on a single Tikhonov parameter. RESULTS: In both the small- and large-tip-angle domain, the simulations show local SAR reductions by over a factor of 2 (4) for a well centered (off-centered) head model at the expense of roughly 1% increment in flip angle spread over the slice. CONCLUSION: Significant SAR reductions can be obtained by optimizing channel-dependent Tikhonov parameters based on the relation between coil elements and SAR hot spot positions. PMID- 21031528 TI - Reconstruction of 3D dynamic contrast-enhanced magnetic resonance imaging using nonlocal means. AB - PURPOSE: To develop and test a nonlocal means-based reconstruction algorithm for undersampled 3D dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) of tumors. MATERIALS AND METHODS: We propose a reconstruction technique that is based on the recently proposed nonlocal means (NLM) filter which can relax trade offs in spatial and temporal resolutions in dynamic imaging. Unlike the original application of NLM for image denoising, the MR reconstruction framework here can offer high-quality images from undersampled k-space data. The method is based on enforcing similarity constraints in terms of neighborhoods of pixels rather than individual pixels. The method was applied on undersampled 3D DCE imaging of breast and brain tumor datasets and the results were compared to sliding window reconstructions and to a compressed sensing method using total variation constraints on the images. RESULTS: Undersampling factors of up to five were obtained with the proposed approach while preserving the spatial and temporal characteristics. The NLM reconstruction method offered improved performance over the sliding window and the total variation constrained reconstruction techniques. CONCLUSION: The reconstruction framework here can give high-quality images from undersampled DCE MRI data and has the potential to improve the quality of DCE tumor imaging. PMID- 21031529 TI - Faster dynamic imaging of speech with field inhomogeneity corrected spiral fast low angle shot (FLASH) at 3 T. AB - PURPOSE: To evaluate the impact of magnetic field inhomogeneity correction on achievable imaging speeds for magnetic resonance imaging (MRI) of articulating oropharyngeal structures during speech and to determine if sufficient acquisition speed is available for visualizing speech structures with real-time MRI. MATERIALS AND METHODS: We designed a spiral fast low angle shot (FLASH) sequence that combines several acquisition techniques with an advanced image reconstruction approach that includes magnetic field inhomogeneity correction. A simulation study was performed to examine the interaction between imaging speed, image quality, number of spiral shots, and field inhomogeneity correction. Six volunteer subjects were scanned to demonstrate adequate visualization of articulating structures during simple speech samples. RESULTS: The simulation study confirmed that magnetic field inhomogeneity correction improves the available tradeoff between image quality and speed. Our optimized sequence co acquires magnetic field maps for image correction and achieves a dynamic imaging rate of 21.4 frames per second, significantly faster than previous studies. Improved visualization of anatomical structures, such as the soft palate, was also seen from the field-corrected reconstructions in data acquired on volunteer subjects producing simple speech samples. CONCLUSION: Adequate temporal resolution of articulating oropharyngeal structures during speech can be obtained by combining outer volume suppression, multishot spiral imaging, and magnetic field corrected image reconstruction. Correcting for the large, dynamic magnetic field variation in the oropharyngeal cavity improves image quality and allows for higher temporal resolution. PMID- 21031530 TI - Magnetic resonance imaging findings in extrauterine malignant mixed Mullerian tumors: report of two cases. AB - This report describes two cases of women who presented with huge abdominal masses. Those lesions were large, invasive, extrauterine masses, which showed inhomogeneous signal intensities at magnetic resonance image (MRI). After work-up and surgery, the masses were identified as extremely rare malignant mixed Mullerian tumors that did not originate from the uterus. We have focused on the MRI findings of the tumors, with a review of the literature. PMID- 21031531 TI - Method for simultaneous voxel-based morphometry of the brain and cervical spinal cord area measurements using 3D-MDEFT. AB - PURPOSE: To investigate whether a 3D-modified driven equilibrium Fourier transform (MDEFT)-based acquisition protocol established for brain morphometry also yields reliable information about the cross-sectional spinal cord area (SCA). MATERIALS AND METHODS: Images of brain and cervical cord of 10 controls and eight subjects with spinal cord injury (SCI) were acquired with the 3D-MDEFT based imaging protocol and an 8-channel receive head coil. The new protocol was validated by two observers 1) comparing the SCA measured with the standard acquisition protocol (3D magnetization-prepared rapid acquisition gradient echo [MPRAGE] and dedicated spine coil) and the new protocol; and 2) determining the scan-rescan reproducibility of the new protocol. RESULTS: Scan-rescan reproducibility of SCA measurements with the MDEFT approach showed a similar precision for both observers with standard deviation (SD) <4.5 mm(2) and coefficient of variation (CV) <=5.1%. Analysis of variance (ANOVA) revealed a main effect of observer and interaction between observer and scan protocol that could be primarily attributed to a small observer bias for MPRAGE (difference in SCA <2.1 mm(2)). No bias was observed for 3D-MDEFT vs. 3D-MPRAGE. CONCLUSION: The 3D-MDEFT method allows for robust unbiased assessment of SCA in addition to brain morphology. PMID- 21031532 TI - Chemical shift imaging in the head and neck at 3T: initial results. AB - PURPOSE: To determine the optimal method to correct air and tissue susceptibility differences in the head and neck to allow proton ((1)H) chemical shift imaging (CSI) to be performed at 3T. MATERIALS AND METHODS: Shimming protocols (iterative, first-order, and second-order) and perfluorocarbon (PFC) pads were evaluated using water peak linewidth measurements obtained from single-voxel magnetic resonance spectroscopy (MRS) on a head and neck phantom. After optimization of the technique, CSI was then tested on 14 patients with head and neck tumors. RESULTS: Second-order shimming (water peak linewidth, 4.6 Hz) performed significantly (P < 0.001) better than first-order (16.5 Hz) and iterative shimming (18 Hz) and the water peak linewidth was significantly reduced using PFC pads (P < 0.001). Using second-order shimming and PFC pads, CSI was successful in 10 patients with nodal metastases (n = 8) and benign tumors (n = 2) and unsuccessful in four patients with primary tumors along the aerodigestive tract. CONCLUSION: Proton CSI can be successfully performed in the head and neck using second-order shimming and PFC pads to correct air and tissue susceptibility differences. CSI was more successfully performed on nodal metastases, while CSI for primary tumors along the aerodigestive tract remains a challenge. PMID- 21031534 TI - Spiral water-fat imaging with integrated off-resonance correction on a clinical scanner. AB - PURPOSE: To integrate water-fat-resolved spiral gradient-echo imaging with off resonance correction into a clinical MR scanner and to evaluate its basic feasibility and performance. MATERIALS AND METHODS: Three-point chemical shift imaging was implemented with forward and strongly T(2)*-weighted reverse spiral sampling and with off-resonance correction after water-fat separation. It was applied in a volunteer study on single breathhold abdominal imaging, which included a brief comparison with Cartesian sampling. RESULTS: Water-fat-resolved, off-resonance-corrected forward and reverse three-dimensional interleaved spiral imaging was found to be feasible on a clinical MR scanner with only minor changes to the existing data acquisition and reconstruction, and to provide good image quality. Three-point chemical shift encoded data thus support both, water-fat separation and off-resonance correction with high accuracy. CONCLUSION: The combination of chemical shift encoding and appropriate postprocessing could pave the way for water-fat-resolved spiral imaging in clinical applications. PMID- 21031533 TI - Noncontrast SSFP pulmonary vein magnetic resonance angiography: impact of off resonance and flow. AB - PURPOSE: To investigate pulmonary vein (PV) off-resonance and blood flow as causes of signal void artifacts in noncontrast steady-state-free-precession (SSFP) PV magnetic resonance angiography (MRA). MATERIALS AND METHODS: PV blood off-resonance was measured on 11 healthy adult subjects and 10 atrial fibrillation (AF) patients. Noncontrast PV MRA was performed using a 3D slab selective SSFP sequence at 1.5T on seven healthy subjects with signal profile shifts of 0-125 Hz. The time-resolved blood flow velocity of the PVs was measured on five healthy subjects. The impact of flow was studied on six healthy subjects, on whom SSFP PV MRA was acquired twice with the electrocardiogram (ECG) trigger delay corresponding to low and high flow, respectively. RESULTS: The PV off resonances were 97 +/- 27 Hz, 65 +/- 20 Hz, 74 +/- 25 Hz, and 52 +/- 17 Hz for right inferior, left inferior, right superior, and left superior PVs, respectively, on healthy subjects, and 74 +/- 20 Hz, 38 +/- 9 Hz, 51 +/- 20 Hz, and 28 +/- 11 Hz on AF patients (P<0.01 for all). The off-resonance caused severe signal voids in the PVs. Signal acquired during mid-diastole with high PV flow caused additional signal voids in the left atrium, which was reduced by setting the ECG trigger delay to late-diastole. CONCLUSION: PV off-resonance and flow causes signal void artifacts in noncontrast 3D slab-selective SSFP PV MRA. PMID- 21031536 TI - Hepatitis B after transplantation: competition between the recipient virus and the donor virus. PMID- 21031537 TI - Post-liver transplant cholestatic hepatitis C: a systematic review of clinical and pathological findings and application of consensus criteria. AB - Liver transplantation is currently the only definitive modality for the treatment of end-stage liver disease due to chronic hepatitis C. However, recurrent hepatitis C after liver transplantation is nearly universal. Cirrhosis may develop in 20% of recipients within 5 years, and recurrent hepatitis C may lead to graft failure, retransplantation, and even death. A subset of recipients may develop post-liver transplant cholestatic hepatitis C (PLTCHC), which is characterized by cholestasis, hepatocyte ballooning, and rapid progression to graft failure. We present a systematic review of PLTCHC that is focused on hepatitis C-infected liver transplant recipients. We compare the pathological definitions of PLTCHC, clinical factors, management strategies, and outcomes reported in studies. We found differences among studies in the types of histological criteria used to diagnose PLTCHC during liver biopsy and in the types of clinical information provided. Three of the 12 studies published after 2003 used the definition of PLTCHC published by the first International Liver Transplantation Society expert panel consensus conference on liver transplantation and hepatitis C. We propose that studies on PLTCHC use the consensus criteria for diagnosis and suggest clinical information that should be provided in future studies with the goal of improving our understanding and management of this deadly disease. PMID- 21031538 TI - Differences in portal hemodynamics between whole liver transplantation and living donor liver transplantation. AB - The aim of this study was to investigate the differences in portal hemodynamics between whole liver transplantation and living donor liver transplantation (LDLT). Twenty patients who underwent LDLT (the L group) and 42 patients who underwent whole liver transplantation (the W group) were enrolled, and colored Doppler ultrasonography was performed preoperatively and on postoperative days (PODs) 1, 3, 5, 7, 30, and 90. The changes in the portal blood flow velocity (PBV) and portal blood flow volume (PBF) were monitored. The graft and spleen sizes were measured with angiographic computed tomography, and upper endoscopy was used to measure esophageal varices on PODs 14, 30, and 90. Although the portal venous pressure (PVP) decreased after graft implantation, it was higher in the L group with a smaller graft size ratio (25.7 +/- 5.1 cm H2O for the L group and 18.5 +/- 4.6 cm H2O for the W group, P < 0.05). PBF and PBV increased in both the W and L groups on POD 1 after transplantation; however, the PBF and PBV peaks were significantly higher in the W group. The postoperative PVP and graft volume were greatly related to PBF on POD 1. Grafts in the L group regenerated rapidly after the operation, and the volume increased from 704 +/- 115 to 1524 +/- 281 mL as early as 1 month after transplantation. A rapid improvement in splenomegaly was observed in both groups. An improvement in esophageal varices was observed in the W group on POD 14 after transplantation, whereas no change was observed in the L group. The portal venous flow in patients with portal hypertension showed a high perfusion state after LDLT, but in contrast to whole liver transplantation, the PVP elevation after LDLT postponed the closing time of the collateral circulation and affected the recovery from splenomegaly. PMID- 21031540 TI - Pretransplant risk factors for new-onset diabetes mellitus after transplant in pediatric liver transplant recipients. AB - Our objectives are to examine the incidence of new-onset diabetes mellitus after transplant (NODAT) and to identify its risk factors in pediatric liver transplant recipients using the Organ Procurement and Transplant Network/United Network for Organ Sharing database. Between July 2004 and December 2008, a total of 1214 children (2-20 years old) received their first liver transplant alone, and had at least 1 follow-up report of posttransplant diabetic status. Among these, 1161 recipients were identified as not having diabetes mellitus before transplant. Risk factors for NODAT were examined using classification and regression tree and multivariate Cox regression analysis. Diabetes mellitus was newly reported in 10.1% of the 1161 recipients over the median follow-up time of 770 days. The cumulative incidences of NODAT at 1, 2, and 3 years after transplant were 5.9%, 8.3%, and 11.2%, respectively. More than 50% of recipients with cystic fibrosis developed NODAT. In recipients without cystic fibrosis, independent risk factors for NODAT included increased recipient age (compared to 2-5 years, hazard ratio = 3.09 for 5-13 years, p = 0.02; 7.14 for >=13 years, p < 0.001), African American race (1.97, p = 0.003), and primary diagnosis of primary sclerosing cholangitis (2.24, p = 0.02) and acute hepatic necrosis (1.89, p = 0.04). In conclusion, NODAT occurred in one-tenth of pediatric liver transplant recipients in the United States during the median follow-up of 2 years. Some of the risk factors for NODAT in pediatric liver transplant recipients are similar to those reported in other solid organ transplants. Underlying liver disease of cystic fibrosis, primary sclerosing cholangitis, and acute hepatic necrosis are independent risk factors for NODAT in pediatric liver transplant recipients. PMID- 21031539 TI - Multivessel coronary artery disease predicts mortality, length of stay, and pressor requirements after liver transplantation. AB - The optimal preoperative cardiac evaluation strategy for patients with end-stage liver disease (ESLD) undergoing liver transplantation remains unknown. Patients are frequently referred for cardiac catheterization, but the effects of coronary artery disease (CAD) on posttransplant mortality are also unknown. We sought to determine the contribution of CAD and multivessel CAD in particular to posttransplant mortality. We performed a retrospective study of ESLD patients undergoing cardiac catheterization before liver transplant surgery between August 1, 2004 and August 1, 2007 to determine the effects of CAD on outcomes after transplantation. Among 83 patients who underwent left heart catheterization, 47 underwent liver transplantation during the follow-up period. Twenty-one of all ESLD patients who underwent liver transplantation (45%) had CAD. Fifteen of the transplant patients with CAD (71%) had multivessel disease. Among transplant patients, the presence of multivessel CAD (versus no CAD) was predictive of mortality (27% versus 4%, P = 0.046), increased length of stay (22 versus 15 days, P = 0.050), and postoperative pressor requirements (27% versus 4%, P = 0.029). Interestingly, neither the presence of any CAD nor the severity of stenosis in any single coronary artery predicted mortality. Furthermore, none of the traditional clinical predictors (age, gender, diabetes, creatinine, ejection fraction, and Model for End-Stage Liver Disease score) were predictive of mortality among transplant recipients. In conclusion, multivessel CAD is associated with higher mortality after liver transplantation when it is documented angiographically before transplantation, even in the absence of severe coronary artery stenosis. This study provides preliminary evidence showing that there may be significant prognostic value in coronary angiography as a part of the pretransplant workup. PMID- 21031541 TI - Neutrophil gelatinase--associated lipocalin predicts acute kidney injury in patients undergoing liver transplantation. AB - Postoperative acute kidney injury (AKI) increases morbidity and mortality after liver transplantation (LT). Novel methods of assessing AKI including cystatin C (CyC) and neutrophil gelatinase-associated lipocalin (NGAL) have been identified as potential markers of AKI. We compare the ability of standard renal markers (serum creatinine [sCr], estimated glomerular filtration rate [eGFR] and intensive therapy unit organ failure scores with CyC and NGAL to predict AKI within the first 48 hours after LT. 95 patients (median age 50 [interquartile range = 41-59], 60% male) underwent LT (25% with acute liver failure). AKI was defined according to the Acute Kidney Injury Network criteria. Severe AKI was classified as >=stage 2. NGAL (urine [u] and plasma [p]) and CyC concentrations taken immediately after transplantation on admission to the Liver Intensive Care Unit were compared with standard markers of renal function. Predictive ability was assessed using the area under the curve generated by receiver operator characteristic analysis (AUROC) and logistic regression. Day 0 sCr, uNGAL, pNGAL, CyC, and eGFR predicted AKI as did SOFA (Sequential Organ Failure Assessment) and APACHE II (Acute Physiology and Chronic Health Evaluation II) scores. APACHE II and pNGAL were the most powerful predictors of severe AKI (APACHE II AUROC = 0.87 [0.77-0.97], P < 0.001; pNGAL AUROC = 0.87 [0.77-0.92], P < 0.001). Using multivariate logistic regression, APACHE II (odds ratio 1.64/point [95% confidence interval = 1.22-2.21, P = 0.001] and pNGAL [odds ratio = 1.01/ng/mL [95% confidence interval = 1.00-1.02], P = 0.002) retained independent significance. A "renal risk score" using APACHE II > 13 and pNGAL > 258 ng/mL was calculated with a score of >=1 having a 100% sensitivity and 76% specificity for severe AKI. In conclusion, a combination of NGAL and APACHE II predicts AKI with high sensitivity and specificity after LT. PMID- 21031543 TI - Hypomagnesemia and the risk of new-onset diabetes after liver transplantation. AB - New-onset diabetes after transplantation (NODAT) is a frequent complication after liver transplantation and has a negative impact on both patient and graft survival. In analogy with the previous finding of an association between posttransplant hypomagnesemia and NODAT in renal transplant recipients, the relation between both pretransplant and posttransplant hypomagnesemia and NODAT was studied in liver transplant recipients (LTRs). One hundred sixty-nine adult LTRs (>18 years old) without diabetes who underwent transplantation between 2004 and 2009 were studied (mean age = 52.11 +/- 12.6 years, proportion of LTRs who were male = 67.5%, body mass index = 25.5 +/- 4.4 kg/m2, proportion receiving tacrolimus = 90.0%). NODAT was defined according to the American Diabetes Association criteria. The association of NODAT with both pretransplant and posttransplant serum magnesium (Mg) was examined. Overall, 52 of 169 patients (30.8%) developed NODAT, and 57.7% of these (30 patients) were treated with antidiabetic drugs. Both pretransplant Mg levels and Mg levels in the first month after transplantation were lower in patients developing NODAT (P = 0.008 and P = 0.001, respectively). A multivariate regression model (adjusted for weight, pretransplant glucose levels, hyperglycemia in the first week after transplantation, gender, hepatitis C, and corticosteroid dosing) demonstrated both pretransplant Mg levels (hazard ratio = 0.844 per 0.1 mg/dL increase, 95% confidence interval = 0.764-0.932, P = 0.001) and posttransplant Mg levels (hazard ratio = 0.659, 95% confidence interval = 0.518-0.838, P = 0.001) to be independent predictors of NODAT together with age, biopsy-proven acute rejection, and cytomegalovirus (CMV) infection in the first year after transplantation. In conclusion, pretransplant hypomagnesemia and early posttransplant hypomagnesemia are independent predictors of new-onset diabetes after liver transplantation. Other risk factors are age, biopsy-proven acute rejection, and CMV infection. PMID- 21031542 TI - Inhibition of inducible nitric oxide synthase prevents graft injury after transplantation of livers from rats after cardiac death. AB - This study investigated the roles of inducible nitric oxide synthase (iNOS) in the failure of rat liver grafts from cardiac death donors (GCDD). Livers were explanted after 30-minute aorta clamping and implanted after 4-hour storage in University of Wisconsin solution. The iNOS expression increased slightly in grafts from non-cardiac death donors (GNCDD) but markedly in GCDD. Serum nitrite and nitrate and hepatic 3-nitrotyrosine adducts, indicators of NO and peroxynitrite production, respectively, were substantially higher after transplantation of GCDD than GNCDD. Production of reactive nitrogen species (RNS) was largely blocked by 1400W (N-[1-naphthyl]ethylenediamine dihydrochloride; 5 MUM), a specific iNOS inhibitor. Alanine aminotransferase release, bilirubin, necrosis, and apoptosis were 6.4-fold, 6.5-fold, 2.3-fold, and 2.7-fold higher, respectively, after transplantation of GCDD than GNCDD. The inhibitor 1400W effectively blocked these alterations and also increased survival of GCDD to 80% from 33%. Increased RNS production and failure of GCDD were associated with activation of c-Jun-N-terminal kinase (JNK), an effect that was blocked by inhibition of iNOS. Inhibition of JNK also improved the outcome after transplantation of GCDD. Together, the data indicate that iNOS increases substantially in GCDD, leading to RNS overproduction, JNK activation, and more severe graft injury. Inhibitors of iNOS are suggested as effective therapies to improve the outcome after transplantation of GCDD. PMID- 21031544 TI - Hepatitis C recurrence is not adversely affected by the use of donation after cardiac death liver allografts. AB - Many factors can worsen a recurrent hepatitis C virus (HCV) infection after liver transplantation (LT). We sought to determine whether the use of donation after cardiac death (DCD) livers affects HCV recurrence. From January 2000 to June 2008, 37 HCV patients underwent LT with DCD allografts. The outcomes and severity of HCV recurrence were analyzed along with those for 74 matched control patients with HCV who received donation after brain death (DBD) livers. The 2 groups had similar donor and recipient characteristics, immunosuppression regimens, rates of acute cellular rejection (ACR), and HCV profiles. DCD patients had a higher incidence of primary nonfunction (19% versus 3%, P = 0.006) and significantly higher peak aspartate aminotransferase levels in comparison with DBD subjects, suggesting a greater degree of ischemia/reperfusion injury. Although the survival rates were not significantly different, DCD recipients had lower 1- and 5-year patient survival rates (83% and 69% versus 84% and 78%, respectively, P = 0.75) and graft survival rates (70% and 61% versus 82% and 74%, respectively, P = 0.24). Three hundred fourteen protocol and clinically indicated liver biopsy procedures were performed within 6 years after transplantation, and mixed modeling analysis showed that fibrosis progression rates were similar for the 2 groups (0.6 fibrosis units/year according to the Ishak modified staging system). The rates of severe HCV recurrence (retransplantation or death due to recurrent hepatitis C and/or the development of stage 4/6 fibrosis or worse within 2 years) were similar [3 DCD patients (8%) versus 11 DBD patients (15%), P = 0.38], and cytomegalovirus infection (hazard ratio = 7.9, P = 0.002, 95% confidence interval = 2.1-28.9) and ACR (hazard ratio = 6.2, P = 0.002, 95% confidence interval = 2.0 19.7) were the only independent risk factors for severe recurrence. In summary, although there was a trend of poorer overall outcomes in DCD patients, the use of DCD livers did not appear to adversely affect HCV recurrence after LT. PMID- 21031545 TI - Impact of obesity on children undergoing liver transplantation. AB - Controversies exist with respect to the mortality of patients undergoing liver transplantation at the extremes of the body mass index (BMI). For pediatric liver transplantation, weight is usually the only factor considered in survival analysis. A review of the United Network for Organ Sharing database (1987-2007) revealed 9701 pediatric patients (<18 years old) who underwent primary liver transplantation. Patients were stratified into 5 BMI categories established by the World Health Organization according to their Z score, which was based on age, gender, and BMI: -3, -2, 0, +2, and +3. The survival rates in these 5 categories were compared with Kaplan-Meier survival curves and log-rank testing. Patients with thinness (Z score = -2) and severe thinness (Z score = -3) had significantly (P < 0.0001) lower survival at 1 year (84.4%) versus the survival (88.7%) of the normal and overweight groups (Z score = 0 and Z score = + 2, respectively). For patients with obesity (Z score = +3), there was no significant difference in survival early after transplantation, but their mortality gradually increased in the later years after transplantation. By 12 years after liver transplantation, the obese group had significantly (P = 0.04) lower survival (72%) than the normal and overweight groups (77%). In conclusion, liver transplantation holds increased risk for obese pediatric patients. Thin pediatric patients experience early mortality after liver transplantation, and obese pediatric patients experience late mortality after liver transplantation. Transplant management can be modified to optimize the care of these patients. PMID- 21031546 TI - Reactive oxygen species mediate human hepatocyte injury during hypoxia/reoxygenation. AB - Increasing evidence shows that reactive oxygen species (ROS) may be critical mediators of liver damage during the relative hypoxia of ischemia/reperfusion injury (IRI) associated with transplant surgery or of the tissue microenvironment created as a result of chronic hepatic inflammation or infection. Much work has been focused on Kupffer cells or liver resident macrophages with respect to the generation of ROS during IRI. However, little is known about the contribution of endogenous hepatocyte ROS production or its potential impact on the parenchymal cell death associated with IRI and chronic hepatic inflammation. For the first time, we show that human hepatocytes isolated from nondiseased liver tissue and human hepatocytes isolated from diseased liver tissue exhibit marked differences in ROS production in response to hypoxia/reoxygenation (H-R). Furthermore, several different antioxidants are able to abrogate hepatocyte ROS-induced cell death during hypoxia and H-R. These data provide clear evidence that endogenous ROS production by mitochondria and nicotinamide adenine dinucleotide phosphate oxidase drives human hepatocyte apoptosis and necrosis during hypoxia and H-R and may therefore play an important role in any hepatic diseases characterized by a relatively hypoxic liver microenvironment. In conclusion, these data strongly suggest that hepatocytes and hepatocyte-derived ROS are active participants driving hepatic inflammation. These novel findings highlight important functional/metabolic differences between hepatocytes isolated from normal donor livers, hepatocytes isolated from normal resected tissue obtained during surgery for malignant neoplasms, and hepatocytes isolated from livers with end-stage disease. Furthermore, the targeting of hepatocyte ROS generation with antioxidants may offer therapeutic potential for the adjunctive treatment of IRI and chronic inflammatory liver diseases. PMID- 21031547 TI - Occult hepatitis B virus infection of donor and recipient origin after liver transplantation despite nucleoside analogue prophylaxis. AB - Liver grafts from donors positive for antibody to hepatitis B core antigen (anti HBc) may be used for transplantation in patients with hepatitis B virus (HBV) related liver disease, and an occult HBV infection may develop from either source. Liver biopsy was performed for 31 patients who remained seronegative for hepatitis B surface antigen for a median of 44.5 months (range = 13.6-126.4 months) and received nucleoside analogue prophylaxis post-transplant. Nineteen of these recipients (61%) had received anti-HBc-positive grafts. Intrahepatic total HBV DNA and covalently closed circular DNA (cccDNA) levels were quantified, and the sequence was analyzed. Intrahepatic total HBV DNA and cccDNA were detectable in 26 (84%) and 16 (52%) of the 31 recipients, respectively, and they were more common when the donor was positive for anti-HBc (95% versus 67%, P = 0.038). The intrahepatic HBV DNA level correlated with the recipient pretransplant serum HBV DNA level (P = 0.06), and the intrahepatic HBV cccDNA level correlated with the donor intrahepatic HBV cccDNA level (P = 0.06). A phylogenetic analysis of the isolated HBV DNA sequence revealed HBV infections of both donor and recipient origins. In conclusion, an occult HBV infection after liver transplantation can originate from both the donor and recipient despite prolonged nucleoside analogue prophylaxis. The presence of intrahepatic HBV cccDNA is attributable more to the persistence of preexisting intrahepatic HBV cccDNA from a donor with previous exposure. PMID- 21031549 TI - Overestimating the liver volume for subjects with low body weight. PMID- 21031548 TI - Primary sclerosing cholangitis in genetically diverse populations listed for liver transplantation: unique clinical and human leukocyte antigen associations. AB - Primary sclerosing cholangitis (PSC) is well characterized in European populations. We aimed to characterize clinical characteristics and human leukocyte antigen (HLA) associations in a population of European American, Hispanic, and African American PSC patients listed for liver transplantation (LT). Population-stratified demographic, clinical, and HLA data from 6767 LT registrants of the United Network for Organ Sharing who had a diagnosis of PSC (4.7% of the registrants) were compared to data from registrants with other diagnoses. Compared to European Americans and Hispanics, African Americans were significantly younger (46.6 +/- 13.7, 42.3 +/- 15.9, and 39.7 +/- 13.1 years, respectively; P = 0.002) and were listed with a higher Model for End-Stage Liver Disease score (15.2 +/- 7.5, 14.9 +/- 7.6, and 18.1 +/- 9.3, respectively; P = 0.001); they were also less frequently noted to have inflammatory bowel disease in comparison with European Americans (71.4% versus 60.5%, P < 0.01). In multivariate analysis, African origin was a significant factor associated with listing for LT with PSC (odds ratio with respect to European Americans = 1.325, 95% confidence interval = 1.221-1.438). HLA associations in European Americans, Hispanics, and African Americans with PSC versus alcoholic liver disease were detected for HLA-B8, HLA-DR13, and protective HLA-DR4. However, HLA-DR3, which is in linkage disequilibrium with HLA-B8, showed associations only in European Americans and Hispanics. In conclusion, African Americans with PSC who are listed for LT differ clinically from European Americans and Hispanics. The association with HLA-B8 but not HLA-DR3 in African Americans should make possible the refinement of the HLA associations in PSC. PMID- 21031550 TI - Feasibility of ABO-incompatible living donor liver transplantation in the rituximab era. PMID- 21031552 TI - Reversal of hepatic myelopathy after liver transplantation: fifteen plus one. PMID- 21031554 TI - Composition of the migratory mass during development of the olfactory nerve. AB - The embryonic development of the olfactory nerve includes the differentiation of cells within the olfactory placode, migration of cells into the mesenchyme from the placode, and extension of axons by the olfactory sensory neurons (OSNs). The coalition of both placode-derived migratory cells and OSN axons within the mesenchyme is collectively termed the "migratory mass." Here we address the sequence and coordination of the events that give rise to the migratory mass. Using neuronal and developmental markers, we show subpopulations of neurons emerging from the placode by embryonic day (E)10, a time at which the migratory mass is largely cellular and only a few isolated OSN axons are seen, prior to the first appearance of OSN axon fascicles at E11. These neurons also precede the emergence of the gonadotropin-releasing hormone neurons and ensheathing glia which are also resident in the mesenchyme as part of the migratory mass beginning at about E11. The data reported here begin to establish a spatiotemporal framework for the migration of molecularly heterogeneous placode-derived cells in the mesenchyme. The precocious emigration of the early arriving neurons in the mesenchyme suggests they may serve as "guidepost cells" that contribute to the establishment of a scaffold for the extension and coalescence of the OSN axons. PMID- 21031556 TI - Cxcr4 and Cxcl12 expression in radial glial cells of the brain of adult zebrafish. AB - Unlike that of mammals, the brain of adult teleost fish exhibits an intense and widespread neurogenic activity as a result of the persistence of radial glial cells acting as neural progenitors throughout life. Because chemokines, notably CXCL12, and their receptors, such as CXCR4, play key roles in mammalian embryonic neurogenesis, we investigated Cxcr4 and Cxcl12 expressions in the brain of adult zebrafish and their potential relationships with cell proliferation. Cxcr4 expression was found to be restricted to radial glial cells in the adult zebrafish, where it is co-expressed with established radial glial cell markers, such as brain lipid-binding protein (Blbp) or the estrogen-synthesizing enzyme aromatase B (Cyp19a1b). Double stainings combining proliferating cell nuclear antigen (PCNA) and Cxcr4 immunolabelling indicated that there is no obvious association between Cxcr4 expression and radial glial cell proliferation. Interestingly, cxcl12a messengers were detected in ventricular regions, in cells corresponding to aromatase B-immunoreactive radial glial cells. Altogether, our data demonstrate Cxcl12 and Cxcr4 expression in radial glial cells of the brain of adult zebrafish, supporting important roles for the Cxcl12/Cxcr4 pair in brain development and functioning. PMID- 21031555 TI - Expression pattern of membrane-associated guanylate kinases in interneurons of the visual cortex. AB - GABAergic interneurons are key elements regulating the activity of local circuits, and abnormal inhibitory circuits are implicated in certain psychiatric and neurodevelopmental diseases. The glutamatergic input that interneurons receive is a key determinant of their activity, yet its molecular structure and development, which are often distinct from those of glutamatergic input to pyramidal cells, are poorly defined. The membrane-associated guanylate kinase (MAGUK) homologs PSD-95/SAP90, PSD-93/chapsyn110, SAP97, and SAP102 are central organizers of the postsynaptic density at excitatory synapses on pyramidal neurons. We therefore studied the cell-type-specific and developmental expression of MAGUKs in the nonoverlapping parvalbumin (PV)- and somatostatin (SOM)-positive interneurons in the visual cortex. These interneuron subtypes account for the vast majority of interneurons in the cortex and have different functional properties and postsynaptic structures, being either axodendritic (PV(+)) or axospinous (SOM(+)). To study cell-type-specific MAGUK expression, we used DIG labeled riboprobes against each MAGUK along with antibodies against either PV or SOM and examined tissue from juvenile (P15) and adult mice. Both PV(+) and SOM(+) interneurons express mRNA for PSD-95, PSD-93, and SAP102 in P15 and adult tissue. In contrast, these interneuron subtypes express SAP97 at P15, but for adult visual cortex we found that most PV(+) and SOM(+) interneurons show low or no expression of SAP97. Given the importance of SAP97 in regulating AMPA receptor GluA1 subunit and NMDA receptor subunits at glutamatergic synapses, these results suggest a developmental shift in glutamate receptor subunit composition and regulation of glutamatergic synapses on PV(+) and SOM(+) interneurons. PMID- 21031557 TI - Subdivisions of the turtle Pseudemys scripta subpallium based on the expression of regulatory genes and neuronal markers. AB - The patterns of distribution of a set of conserved brain developmental regulatory transcription factors and neuronal markers were analyzed in the subpallium of the juvenile turtle, Pseudemys scripta. Immunohistochemical techniques were used with a combination of primary antibodies for the identification of the main boundaries and subdivisions in the basal telencephalon. In the basal ganglia, the combinatorial expression on Pax6, Nkx2.1, and GABA was a powerful tool for the identification of the nucleus accumbens, the dorsal portion of the striatum, and the pallidal regions. It was also possible to suggest migratory streams of neurons from the pallidum into the striatal regions. On the basis of GABA, Pax6, Tbr1, tyrosine hydroxylase, Darpp32, and Nkx2.1 combinatorial expression patterns, the boundaries of the septal subdivisions and their embryological origin were assessed. In particular, the bed nucleus of the stria terminalis was identified. Within the amygdaloid complex, the striatal central amygdala was characterized by Pax6 expression, whereas Orthopedia gene expression highlighted, at least, a subdivision of the medial amygdala. A newly identified preoptic commissural area and the boundaries of the preoptic area were assessed, mainly by the localization of Nkx2.1 expression. Finally, additional data were obtained by combining immunohistochemistry and tracing techniques on the interneuronal nature of the cholinerginergic, nitrergic, and Nkx2.1-positive striatal cells. Taken together, all the results of the present study allowed recognizing main features in the organization of the subpallium in reptiles that, in most cases, are shared with other amniotes and amphibians. PMID- 21031558 TI - Cholinergic inputs to laryngeal motoneurons functionally identified in vivo in rat: a combined electrophysiological and microscopic study. AB - The intrinsic laryngeal muscles are differentially modulated during respiration as well as other states and behaviors such as hypocapnia and sleep. Previous anatomical and pharmacological studies indicate a role for acetylcholine at the level of the nucleus ambiguus in the modulation of laryngeal motoneuron (LMN) activity. The present study investigated the anatomical nature of cholinergic input to inspiratory- (ILM) and expiratory-modulated (ELM) laryngeal motoneurons in the loose formation of the nucleus ambiguus. Using combined in vivo intracellular recording, dye filling, and immunohistochemistry, we demonstrate that LMNs identified in Sprague-Dawley rat receive several close appositions from vesicular acetylcholine transporter-immunoreactive (VAChT-ir) boutons. ELMs receive a significantly greater number of close appositions (mean +/- standard deviation [SD]: 47 +/- 11; n = 5) than ILMs (32 +/- 9; n = 8; t-test P < 0.05). For both LMN types, more close appositions were observed on the cell soma and proximal dendrites compared to distal dendrites (two-way analysis of variance [ANOVA], P < 0.0001). Using fluorescence confocal microscopy, almost 90% of VAChT ir close appositions (n = 45 boutons on n = 4 ELMs) were colocalized with the synaptic marker synaptophysin. These results support a strong influence of cholinergic input on LMNs and may have implications in the differential modulation of laryngeal muscle activity. PMID- 21031559 TI - GABAergic complex basket formations in the human neocortex. AB - Certain GABAergic interneurons in the cerebral cortex, basket cells, establish multiple connections with cell bodies that typically outline the somata and proximal dendrites of pyramidal cells. During studies into the distribution of the vesicular GABA transporter (VGAT) in the human cerebral cortex, we were struck by the presence of a very dense, pericellular arrangement of multiple VGAT immunoreactive (-ir) terminals in certain cortical areas. We called these terminals "Complex basket formations" (Cbk-formations) to distinguish them from the simpler and more typical pericellular GABAergic innervations of most cortical neurons. Here we examined the distribution of these VGAT-ir Cbk-formations in various cortical areas, including the somatosensory (area 3b), visual (areas 17 and 18), motor (area 4), associative frontal (dorsolateral areas 9, 10, 45, 46, and orbital areas 11, 12, 13, 14, 47), associative temporal (areas 20, 21, 22, and 38), and limbic cingulate areas (areas 24, 32). Furthermore, we used dual or triple staining techniques to study the chemical nature of the innervated cells. We found that VGAT-ir Cbk-formations were most frequently found in area 4 followed by areas 3b, 13, and 18. In addition, they were mostly observed in layer III, except in area 17, where they were most dense in layer IV. We also found that 70% of the innervated neurons were pyramidal cells, while the remaining 30% were multipolar cells. Most of these multipolar cells expressed the calcium binding protein parvalbumin and the lectin Vicia villosa agglutinin. PMID- 21031560 TI - Alternative splicing of neuroligin and its protein distribution in the outer plexiform layer of the chicken retina. AB - Although synaptogenesis within the retina is obviously essential for vision, mechanisms responsible for the initiation and maintenance of retinal synapses are poorly understood. In addition to its scientific interest, understanding retinal synapse formation is becoming clinically relevant with ongoing efforts to develop transplantation-based approaches for the treatment of retinal degenerative disease. To extend our understanding, we have focused on the chick model system and have studied the neuroligin family of neuronal adhesion factors that has been shown to participate in synapse assembly in the brain. We identified chicken orthologs of neuroligins 1, -3, and -4, but could find no evidence of neuroligin 2. We investigated temporal and spatial patterns of mRNA and protein expression during development using standard polymerase chain reaction (RT-PCR), quantitative PCR (QPCR), laser-capture microdissection (LCM), and confocal microscopy. At the mRNA level, neuroligins were detected at the earliest period tested, embryonic day (ED)5, which precedes the period of inner retina synaptogenesis. Significant alternative splicing was observed through development. While neuroligin gene products were generally detected in the inner retina, low levels of neuroligin 1 mRNA were also detected in the photoreceptor layer. Neuroligin 3 and -4 transcripts, on the other hand, were only detected in the inner retina. At retinal synapses neuroligin 1 protein was detected in the inner plexiform layer, but its highest levels were detected in the outer plexiform layer on the tips of horizontal cell dendrites. This work lays the groundwork for future studies on the functional roles of the neuroligins within the retina. PMID- 21031563 TI - Paraoxonase 1 polymorphisms and haplotypes and the risk for having offspring affected with spina bifida in Southeast Mexico. AB - BACKGROUND: Spina bifida (SB) is a common congenital malformation in Southeast Mexico. Parents of children with SB reside in areas with frequent pesticide spraying or have agriculture activities, suggesting potential exposure to pesticides. Paraoxonase 1 (PON1) is the responsible enzyme for deactivation of organophosphates (OP) in the central nervous system. Polymorphisms of PON1 genes influence the catalytic activity and plasma protein level of the enzyme, therefore, genotypic characterization of PON1 gene represents a potential predictor for susceptibility to OP-related effects. METHODS: The frequency of PON1 haplotypes and polymorphisms (-108CT, L55M, and Q192R) were determined in this study. A case-control study was performed to evaluate the risk for having offspring affected by SB in 152 cases and 160 control parents. Polymorphisms were determined by PCR amplification and restriction fragment length polymorphism and Real Time-PCR. Odds ratios and confidence interval 95% were estimated. RESULTS: Genotype frequencies for the three PON1 polymorphisms were distributed according to Hardy-Weinberg expectations (p > 0.05) and were significantly different between cases and controls (p < 0.05). The heterozygous CT genotype of -108CT polymorphism, the RR genotype of Q192R polymorphism, both LM and MM genotypes of L55M polymorphism, and the haplotypes 221 and 222 (for -108CT, L55M, and Q192R) were associated with the risk for having a child affected by SB (p < 0.02). The heterozygous -108CT genotype was associated only maternally, whereas the heterozygous L55M genotype was relevant only in the fathers. The RR homozygous genotype was relevant both in mothers and fathers, suggesting the importance of this substrate-specific polymorphism. CONCLUSION: Results suggest that PON1 polymorphisms are relevant risk factors for having offspring affected with SB in this population from Southeast Mexico. PMID- 21031562 TI - Role of the Nav1.7 R1150W amino acid change in susceptibility to symptomatic knee osteoarthritis and multiple regional pain. AB - OBJECTIVE: To assess the genetic association of pain in patients with knee osteoarthritis (OA) and those with multiple regional pain with the R1150W variant in the alpha-subunit of the voltage-gated sodium channel Na(V)1.7. METHODS: Knee OA patients from 2 UK cohorts (1,411 from the Genetics of Osteoarthritis and Lifestyle study and 267 from the Hertfordshire Cohort Study; 74% with symptomatic OA) with Western Ontario and McMaster Universities OA Index (WOMAC) pain scores were genotyped for rs6746030 (encoding the R1150W change). One hundred seventy six knee OA patients (53% symptomatic) from the Clearwater Osteoarthritis Study were also tested. A total of 4,295 samples (both affected and unaffected OA) from all 3 studies with data on multiple regional pain were tested. Fixed-effects meta analyses were carried out with the WOMAC, symptomatic OA (adjusting for radiographic severity), and multiple regional pain as outcomes. RESULTS: No association with the WOMAC was seen in the UK cohorts. Overall, the meta-analysis of WOMAC yielded a summary statistic of beta = 0.47 (95% confidence interval [95% CI] 0.04, 0.89; P = 0.030) for the variant allele. The meta-analysis of symptomatic versus asymptomatic OA did not demonstrate an association with rs6746030 (odds ratio [OR] 0.90 [95% CI 0.71, 1.15], P = 0.38). The meta-analysis of multiple regional pain resulted in a significant OR of 1.40 (95% CI 1.08, 1.80; P = 0.0085). No interstudy heterogeneity was seen for any of the analyses. CONCLUSION: We find evidence that the R1150W amino acid change in the Na(V)1.7 alpha-chain is associated with multiple regional pain. This variant is confirmed to be involved in genetic susceptibility to pain, but it does not appear to have a major role in OA-specific pain. PMID- 21031561 TI - Role of interstitial branching in the development of visual corticocortical connections: a time-lapse and fixed-tissue analysis. AB - We combined fixed-tissue and time-lapse analyses to investigate the axonal branching phenomena underlying the development of topographically organized ipsilateral projections from area 17 to area 18a in the rat. These complementary approaches allowed us to relate static, large-scale information provided by traditional fixed-tissue analysis to highly dynamic, local, small-scale branching phenomena observed with two-photon time-lapse microscopy in acute slices of visual cortex. Our fixed-tissue data revealed that labeled area 17 fibers invaded area 18a gray matter at topographically restricted sites, reaching superficial layers in significant numbers by postnatal day 6 (P6). Moreover, most parental axons gave rise to only one or occasionally a small number of closely spaced interstitial branches beneath 18a. Our time-lapse data showed that many filopodium-like branches emerged along parental axons in white matter or deep layers in area 18a. Most of these filopodial branches were transient, often disappearing after several minutes to hours of exploratory extension and retraction. These dynamic behaviors decreased significantly from P4, when the projection is first forming, through the second postnatal week, suggesting that the expression of, or sensitivity to, cortical cues promoting new branch addition in the white matter is developmentally down-regulated coincident with gray matter innervation. Together, these data demonstrate that the development of topographically organized corticocortical projections in rats involves extensive exploratory branching along parental axons and invasion of cortex by only a small number of interstitial branches, rather than the widespread innervation of superficial cortical layers by an initially exuberant population of branches. PMID- 21031565 TI - From Lowe syndrome to Dent disease: correlations between mutations of the OCRL1 gene and clinical and biochemical phenotypes. AB - Mutations of OCRL1 are associated with both the Lowe oculocerebrorenal syndrome, a multisystemic and Dent-2 disease, a renal tubulopathy. We have identified a mutation in 130 Lowe syndrome families and 6 affected by Dent-2 disease with 51 of these mutations being novel. No founding effect was evidenced for recurrent mutations. Two mutations initially reported as causing Dent-2 disease were identified in patients, including two brothers, presenting with Lowe syndrome thus extending the clinical variability of OCRL1 mutations. mRNA levels, protein content, and PiP(2) -ase activities were analyzed in patient's fibroblasts. Although mRNA levels were normal in cells harboring a missense mutation, the OCRL1 content was markedly lowered, suggesting that enzymatic deficiency resulted mainly from protein degradation rather than from a catalytic inactivation. Analysis of a splicing mutation that led to the elimination of the initiation codon evidenced the presence of shortened forms of OCRL1 that might result from the use of alternative initiation codons. The specific mapping of the frameshift and nonsense mutations, exclusively identified in exons 1-7 and exons 8-23, respectively, for Dent disease and Lowe syndrome together with the possible use of alternative initiation codons might be related to their clinical expression, that is, Lowe syndrome or Dent-2 disease. PMID- 21031566 TI - NerveCenter: Unintended effects of biologic drug market protection. AB - Market exclusivity given to biologics puts burdens on healthcare and new development. PMID- 21031569 TI - NerveCenter: Are IPSCs a game-changer in stem cell debate? AB - Public and private investment in induced pluripotent stem cell research is likely to have major benefits for health; however human embryonic stem cell research remains essential. PMID- 21031570 TI - Delivery of myelin peptides through the first line of defense, skin, to counter autoimmunity in multiple sclerosis. PMID- 21031571 TI - Measuring language recovery in the underlying large-scale neural network: Pulling together in the face of adversity. PMID- 21031572 TI - Primary central nervous system vasculitis: Is it a single disease? PMID- 21031573 TI - Three faces of the same gene: FA2H links neurodegeneration with brain iron accumulation, leukodystrophies, and hereditary spastic paraplegias. PMID- 21031574 TI - L-3,4-dihydroxyphenylalanine-induced sprouting of serotonin axon terminals: A useful biomarker for dyskinesias? PMID- 21031575 TI - Imaging the future of stroke: II. Hemorrhage. AB - Bleeding into the brain or adjacent structures is one of the most devastating neurological conditions, incurring tremendous emotional, financial, and societal costs. Imaging is essential to differentiate variants of hemorrhage, as the clinical features may be insufficient. A comprehensive approach to hemorrhage therefore relies on imaging to disclose pathophysiology, elucidate mechanisms, and thereby open further avenues to effective treatment. Hemorrhage patterns from superficial to deep locations in the brain are surveyed in this work, noting myriad potential causes and the influential pathophysiology of arterial ischemia, venous hypertension, and microvascular dysfunction. Recent progress of imaging studies and novel techniques to evaluate hemorrhage are explored. For decades, only computed tomography was available to define a hematoma without corroborating evidence of other pathology whereas multimodal computed tomography and magnetic resonance imaging, including noninvasive imaging of brain tissue, vessels, and perfusion, have now radically altered clinical practice. Imaging of the blood brain barrier, cerebral microbleeds, coexistent ischemia, associated vascular lesions, and markers of hemorrhage expansion is possible with routine protocols akin to diagnostic strategies for ischemic stroke. Imaging applications for hemorrhagic transformation, venous thrombosis, and microvascular disorders are considered with a perspective that balances concern for hemorrhage with prevention of ischemia as these processes are often intertwined and clinical conundrums arise. Imminent imaging advances are anticipated with increased use of detailed imaging for hemorrhage and overlap with cerebral ischemia. Numerous questions abound regarding optimal management of hemorrhage and definitive treatments are lacking, yet imaging of pivotal pathophysiology offers tremendous opportunity for future progress in combating this debilitating condition. PMID- 21031576 TI - Immune regulation of multiple sclerosis by transdermally applied myelin peptides. AB - OBJECTIVE: Antigen-specific therapy targeting selective inhibition of autoreactive responses holds promise for controlling multiple sclerosis (MS) without disturbing homeostasis of the whole immune system. Key autoantigens in MS include myelin proteins, such as myelin basic protein (MBP), proteolipid protein (PLP), and myelin oligodendrocyte glycoprotein (MOG). In this study, we examined the effect of transdermal therapy with myelin peptides on immune responses in the skin, lymph nodes, and peripheral blood immune cells of MS patients. METHODS: In a 1-year placebo-controlled study, 30 patients with relapsing-remitting MS were treated transdermally with a mixture of 3 myelin peptides: MBP85-99, PLP139-151, and MOG35-55, or placebo. The phenotype of immune cells in the skin was assessed using immunohistochemistry. Cell populations in lymph nodes were analyzed using flow cytometry. In peripheral blood immune cells, cytokine production was measured by enzyme-linked immunosorbent assay, and myelin-specific proliferation was examined by carboxyfluorescein succinimidyl ester-based assay. RESULTS: We found that myelin peptides applied transdermally to MS patients activated dendritic Langerhans cells in the skin at the site of immunization and induced a unique population of granular dendritic cells in local lymph nodes. In the periphery, transdermal immunization with myelin peptides resulted in the generation of type 1, interleukin-10-producing regulatory T cells, suppression of specific autoreactive proliferative responses, and suppression of interferon gamma and transforming growth factor-beta production. INTERPRETATION: We demonstrate for the first time the immunoregulatory potential of transdermal immunization with myelin peptides in MS patients. PMID- 21031577 TI - Brain biopsy in children with primary small-vessel central nervous system vasculitis. AB - OBJECTIVE: Primary angiitis of the central nervous system in childhood (cPACNS) is an immune-mediated inflammatory process directed toward blood vessels in the central nervous system. It has been associated with variable clinical and radiological presentations, and devastating consequences without treatment. Brain biopsy is required for definitive diagnosis. The objective of this study was to characterize the clinical and histopathological features of brain biopsies in small-vessel cPACNS (SVcPACNS). METHODS: A single-center prospective cohort study of children diagnosed with cPACNS from 1998 to 2008 was performed. All patients with negative cerebral angiography and brain biopsy were included. Patient data were reviewed for clinical, laboratory, and radiological characteristics at presentation. Standardized brain biopsy review protocols were established, with independent analysis by 2 neuropathologists. Histopathology was correlated with collected clinical data. RESULTS: A total of 13 SVcPACNS patients were included. Ages ranged from 5 to 17 years. Presenting features included seizures (85%), headache (62%), and cognitive decline (54%). Brain biopsy confirmed SVcPACNS in 11 patients with intramural lymphocytic infiltrate. Two had nonspecific perivascular inflammation only. All 6 nonlesional biopsies yielded a diagnosis of SVcPACNS. Lack of specific histological features correlated with prolonged time to biopsy, prior steroid treatment, and inadequate specimen sampling. INTERPRETATION: In children presenting with new onset severe headaches, seizures, or cognitive decline, SVcPACNS and brain biopsy should be considered. Lesional biopsies are preferred; however, nonlesional biopsies may succeed in yielding the diagnosis. Steroid treatment prior to biopsy and inadequate biopsy sampling may obscure the diagnosis in true cases of SVcPACNS. PMID- 21031578 TI - Sustained alpha-sarcoglycan gene expression after gene transfer in limb-girdle muscular dystrophy, type 2D. AB - OBJECTIVE: The aim of this study was to attain long-lasting alpha-sarcoglycan gene expression in limb-girdle muscular dystrophy, type 2D (LGMD2D) subjects mediated by adeno-associated virus (AAV) gene transfer under control of a muscle specific promoter (tMCK). METHODS: rAAV1.tMCK.hSGCA (3.25 * 1011 vector genomes) was delivered to the extensor digitorum brevis muscle of 3 subjects with documented SGCA mutations via a double-blind, randomized, placebo controlled trial. Control sides received saline. The blind was not broken until the study was completed at 6 months and all results were reported to the oversight committee. RESULTS: Persistent alpha-sarcoglycan gene expression was achieved for 6 months in 2 of 3 LGMD2D subjects. Markers for muscle fiber transduction other than alpha-sarcoglycan included expression of major histocompatibility complex I, increase in muscle fiber size, and restoration of the full sarcoglycan complex. Mononuclear inflammatory cells recruited to the site of gene transfer appeared to undergo programmed cell death, demonstrated by terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate nick-end labeling and caspase-3 staining. A patient failing gene transfer demonstrated an early rise in neutralizing antibody titers and T-cell immunity to AAV, validated by enzyme linked immunospot on the second day after gene injection. This was in clear distinction to other participants with satisfactory gene expression. INTERPRETATION: The findings of this gene replacement study in LGMD2D subjects have important implications not previously demonstrated in muscular dystrophy. Long-term, sustainable gene expression of alpha-sarcoglycan was observed following gene transfer mediated by AAV. The merit of a muscle-specific tMCK promoter, not previously used in a clinical trial, was evident, and the potential for reversal of disease was displayed. PMID- 21031579 TI - Sigma nonopioid intracellular receptor 1 mutations cause frontotemporal lobar degeneration-motor neuron disease. AB - OBJECTIVE: Frontotemporal lobar degeneration (FTLD) is the most common cause of early-onset dementia. Pathological ubiquitinated inclusion bodies observed in FTLD and motor neuron disease (MND) comprise trans-activating response element (TAR) DNA binding protein (TDP-43) and/or fused in sarcoma (FUS) protein. Our objective was to identify the causative gene in an FTLD-MND pedigree with no mutations in known dementia genes. METHODS: A mutation screen of candidate genes, luciferase assays, and quantitative polymerase chain reaction (PCR) was performed to identify the biological role of the putative mutation. Neuropathological characterization of affected individuals and western blot studies of cell lines were performed to identify the pathological mechanism of the mutation. RESULTS: We identified a nonpolymorphic mutation (c.672*51G>T) in the 3'-untranslated region (UTR) of the Sigma nonopioid intracellular receptor 1 (SIGMAR1) gene in affected individuals from the FTLD-MND pedigree. The c.672*51G>T mutation increased gene expression by 1.4-fold, corresponding with a significant 1.5-fold to 2-fold change in the SIGMAR1 transcript or Sigma-1 protein in lymphocyte or brain tissue. Brains of SIGMAR1 mutation carriers displayed a unique pathology with cytoplasmic inclusions immunopositive for either TDP-43 or FUS but not Sigma 1. Overexpression of SIGMAR1 shunted TDP-43 and FUS from the nucleus to the cytoplasm by 2.3-fold and 5.2-fold, respectively. Treatment of cells with Sigma-1 ligands significantly altered translocation of TDP-43 by up to 2-fold. INTERPRETATION: SIGMAR1 is a causative gene for familial FTLD-MND with a unique neuropathology that differs from other FTLD and MND cases. Our findings also suggest Sigma-1 drugs as potential treatments for the TDP-43/FUS proteinopathies. PMID- 21031581 TI - Recurrent ischemic events in young adults after first-ever ischemic stroke. AB - OBJECTIVE: Data on recurrence of vascular events and their prognostic factors in young (<50 years of age) stroke patients are not well defined. METHODS: We assessed the occurrence of arterial thrombotic events in consecutive first-ever ischemic stroke patients aged 15 to 49 years entered into the Helsinki Young Stroke Registry (January 1994-October 2004) within 5-year follow-up. Follow-up was conducted with a structured telephone interview or letter, and review of all patient records; mortality data came from Statistics Finland. Primary outcomes were (1) nonfatal or fatal recurrent ischemic stroke; (2) nonfatal or fatal myocardial infarct, other arterial thrombotic event, or revascularization procedure; and (3) any combination of these, whichever occurred first (composite endpoint). We used Kaplan-Meier analysis to estimate cumulative risks and Cox proportional hazard model-adjusted for age, gender, relevant risk factors, and stroke subtype-for identifying predictors of recurrence. RESULTS: In the 807 patients followed (mean age, 41.5 +/- 7.4 years; 62.9% male), cumulative 5-year recurrence rate was 9.4% (95% confidence interval [CI], 7.3-11.5%) for nonfatal or fatal ischemic stroke, 2.4% (95% CI, 1.3-3.5%) for nonfatal or fatal myocardial infarct or other arterial endpoint, and 11.5% (95% CI, 9.2-13.7%) for the composite endpoint. Independent predictors of the composite endpoint were type 1 diabetes mellitus (hazard ratio [HR], 4.39; 95% CI, 2.28-8.45), large artery atherosclerosis underlying the index stroke (HR, 2.82; 95% CI, 1.36-5.83), heart failure (HR, 2.96; 95% CI, 1.17-7.50), previous transient ischemic attack (HR, 2.33; 95% CI, 1.40-3.88), and increasing age (HR, 1.05; 95% CI, 1.01-1.10). INTERPRETATION: Despite their young age, these individuals were at marked risk of recurrent arterial events, predicted by mostly modifiable baseline factors. PMID- 21031580 TI - Recombinant osteopontin in cerebral vasospasm after subarachnoid hemorrhage. AB - OBJECTIVE: Osteopontin (OPN), a pleiotropic extracellular matrix glycoprotein, has been reported to be protective against ischemic lesions, but effects of OPN on vascular functions have not been investigated. The aim of this study was to assess whether recombinant OPN (r-OPN) could prevent cerebral vasospasm after subarachnoid hemorrhage (SAH) in rats. METHODS: r-OPN was administered intraventricularly to rats undergoing SAH by endovascular perforation, and its protective effects were evaluated by measuring the diameter of cerebral arteries and neurobehavioral testing. Western blotting and immunofluorescence were performed to explore the underlying mechanisms. An integrin receptor antagonist GRGDSP or mitogen-activated protein kinase (MAPK) phosphatase (MKP)-1 small interfering RNA (siRNA) was also administered to r-OPN-treated SAH rats, and those effects were evaluated. RESULTS: Pre-SAH administration of r-OPN prevented vasospasm and neurological impairments at 24-72 hours post-SAH. r-OPN enhanced an endogenous MAPK inhibitor, MKP-1, and suppressed the phosphorylation of MAPKs, caldesmon, and heat shock protein 27 in the spastic cerebral arteries at 24 hours post-SAH. Immunofluorescence revealed that MKP-1 was induced in the arterial smooth muscle layer. GRGDSP prevented r-OPN-induced MKP-1 upregulation, and MKP-1 siRNA abolished both MAPK inactivation and anti-vasospastic effects by r-OPN. Post-SAH r-OPN treatment also prevented vasospasm. INTERPRETATION: r-OPN induced MKP-1 in the spastic cerebral arteries via binding to L-arginyl-glycyl-L aspartate-dependent integrin receptors and prevented vasospasm after SAH. Therapeutic induction of MKP-1 may be a novel approach for the prevention and treatment of cerebral vasospasm. PMID- 21031582 TI - Elevated plasma YKL-40 levels and ischemic stroke in the general population. AB - OBJECTIVE: We hypothesized that elevated plasma YKL-40 levels are associated with increased risk of ischemic cardiovascular disease in the general population. In contrast to C-reactive protein (CRP) produced in the liver in response to inflammation, YKL-40 is produced by lipid-laden macrophages inside the vessel wall. METHODS: We measured plasma YKL-40 in 8,899 21- to 93-year-old participants of the Copenhagen City Heart Study 1991-1994 examination, and followed them for up to 18 years. Endpoints were ischemic stroke, ischemic cerebrovascular disease, myocardial infarction, and ischemic heart disease. Hazard ratios were calculated for plasma YKL-40 levels in 10-year age percentile categories of 34 to 66%, 67 to 90%, and 91 to 100% versus 0 to 33%. RESULTS: Multifactorially and CRP-adjusted hazard ratios for ischemic stroke were 1.2 (95% confidence interval, 0.9-1.6) for 33 to 66%, 1.8 (1.3-2.4) for 67 to 90%, and 2.3 (1.5-3.3) for 91 to 100% versus the 0 to 33% percentile category (p-trend < 0.001). Corresponding hazard ratios for ischemic cerebrovascular disease were 1.2 (0.9-1.5), 1.6 (1.2-2.0), and 2.2 (1.6-3.2) (p-trend < 0.001). Hazard ratios for myocardial infarction were not significant, whereas corresponding hazard ratios for ischemic heart disease were 1.0 (0.8-1.2), 1.2 (1.0-1.5), and 1.3 (1.0-1.6) (p-trend = 0.01). Stratifying for CRP or other risk factors gave similar results. A doubling in plasma YKL-40 was associated with multifactorially and CRP-adjusted increased risk of 20% (95% confidence interval, 11%-30%) for ischemic stroke, 16% (8%-24%) for ischemic cerebrovascular disease, 3% (-5%-11%) for myocardial infarction, and 7% (1%-12%) for ischemic heart disease. INTERPRETATION: In the general population, elevated plasma YKL-40 levels are associated with increased risk of ischemic stroke and ischemic cerebrovascular disease, independent of plasma CRP levels. PMID- 21031583 TI - Signatures of cardioembolic and large-vessel ischemic stroke. AB - OBJECTIVE: The cause of stroke remains unknown or cryptogenic in many patients. We sought to determine whether gene expression signatures in blood can distinguish between cardioembolic and large-vessel causes of stroke, and whether these profiles can predict stroke etiology in the cryptogenic group. METHODS: A total of 194 samples from 76 acute ischemic stroke patients were analyzed. RNA was isolated from blood and run on Affymetrix U133 Plus2.0 microarrays. Genes that distinguish large-vessel from cardioembolic stroke were determined at 3, 5, and 24 hours following stroke onset. Predictors were evaluated using cross validation and a separate set of patients with known stroke subtype. The cause of cryptogenic stroke was predicted based on a model developed from strokes of known cause and identified predictors. RESULTS: A 40-gene profile differentiated cardioembolic stroke from large-vessel stroke with >95% sensitivity and specificity. A separate 37-gene profile differentiated cardioembolic stroke due to atrial fibrillation from nonatrial fibrillation causes with >90% sensitivity and specificity. The identified genes elucidate differences in inflammation between stroke subtypes. When applied to patients with cryptogenic stroke, 17% are predicted to be large-vessel and 41% to be cardioembolic stroke. Of the cryptogenic strokes predicted to be cardioembolic, 27% were predicted to have atrial fibrillation. INTERPRETATION: Gene expression signatures distinguish cardioembolic from large-vessel causes of ischemic stroke. These gene profiles may add valuable diagnostic information in the management of patients with stroke of unknown etiology though they need to be validated in future independent, large studies. PMID- 21031584 TI - Natural history of incidental World Health Organization grade II gliomas. AB - OBJECTIVE: Seizure is the presenting symptom in most of World Health Organization grade II gliomas (GIIGs). Rarely, a GIIG is discovered incidentally on imaging. Little is known about the natural course and prognosis of incidental GIIGs. The aim of the present study is to characterize their natural history and to investigate whether their clinical and radiological behaviors differ from those of symptomatic GIIGs. METHODS: The clinical and radiological findings, treatments, and outcomes of 47 histologically-proven incidental GIIGs were compared with those of 1249 symptomatic GIIGs. RESULTS: Incidental GIIGs differ significantly from symptomatic GIIGs: they have a female predominance (p = 0.05), smaller initial tumor volumes (p < 0.001), lower incidence of contrast enhancement (p = 0.009), and are more likely to undergo gross total surgical removal (p < 0.001). Proliferation rates were similar to that observed among symptomatic GIIGs. Younger age at the time of discovery, frontal lobes, and noneloquent brain regions were associated with incidental GIIGs, as compared to their symptomatic counterparts. When not treated, incidental GIIGs demonstrated radiological growth (median velocity of diametric expansion at 3.5 mm/year), and became symptomatic at a median interval of 48 months after radiological discovery. Overall, incidental discovery was associated with a significant survival benefit (p = 0.04). INTERPRETATION: Incidental GIIGs are progressive tumors leading to clinical transformation toward symptomatic GIIGs. They may represent an earlier step in the natural history of a glioma than the symptomatic GIIGs. PMID- 21031585 TI - Caffeine and brain development in very preterm infants. AB - OBJECTIVE: Caffeine improves neurological outcome in very preterm infants, but the mechanisms responsible for this neurological benefit are unknown. The objective of this study was to assess whether caffeine influenced brain macro- or microstructural development in preterm infants. METHODS: Seventy preterm infants <1,251 g birthweight randomly allocated to either caffeine (n = 33) or placebo (n = 37) underwent brain magnetic resonance imaging (MRI) at term-equivalent age; white and gray matter abnormalities were qualitatively scored, global and regional brain volumes were measured, and white matter microstructure was evaluated using diffusion-weighted imaging. RESULTS: There were no significant differences between the groups in the extent of white matter or gray matter abnormality, or in global or regional brain volumes. In contrast, although only available in 28 children, caffeine exposure was associated with reductions in the apparent diffusion coefficient, and radial and axial diffusivity with the greatest impact in the superior brain regions. The alterations in diffusion measures were not mediated by lowering the rate of lung injury, known as bronchopulmonary dysplasia. INTERPRETATION: These diffusion changes are consistent with improved white matter microstructural development in preterm infants who received caffeine. PMID- 21031586 TI - Use of guidelines improves the neurological outcome in glutaric aciduria type I. AB - OBJECTIVE: To evaluate the effect of treatment according to current evidence based recommendations on the neurological outcome of patients with glutaric aciduria type I (GA-I). METHODS: Fifty-two patients identified by newborn screening (NBS) in Germany from 1999 to 2009 were followed prospectively. Neurological outcome was assessed by the occurrence of an acute encephalopathic crisis and the severity of a movement disorder (MD) with predominant dystonia superimposing on axial hypotonia. Outcome was evaluated in relation to therapy and therapy-independent parameters. RESULTS: Outcome was best in GA-I patients who were treated in full accordance with treatment recommendations (n=37; 5% MD). Deviations from recommended basic metabolic treatment (low-lysine diet, carnitine) resulted in an intermediate outcome (n=9; 44% MD), whereas disregard of emergency treatment recommendations was associated with a poor outcome (n=6; 100% MD). Treatment regimens deviating from recommendations significantly increased the risk for MD (odds ratio [OR], 35; 95% confidence interval [CI], 5.88-208.39) and acute encephalopathic crises (OR, 51.32; 95% CI, 2.65-993.49). Supervision by a metabolic center improved the outcome (18% vs 57% MD; OR, 6.17; 95% CI, 1.15-33.11), whereas migrational background and biochemical phenotype (high versus low excretor status) had no significant effect. INTERPRETATION: Follow-up of neonatally diagnosed patients with GA-I in Germany clearly demonstrates that the inclusion of this rare disease in the NBS disease panel has significantly improved the neurological outcome of affected individuals. The establishment of and adherence to evidence-based treatment recommendations, and supervision by experienced metabolic centers helps to minimize the number of patients who do not benefit from NBS. PMID- 21031587 TI - Intractable vomiting as the initial presentation of neuromyelitis optica. AB - We report 12 aquaporin-4 antibody-positive patients (12% of seropositive Mayo Clinic patients identified since 2005) whose initial presenting symptom of neuromyelitis optica was intractable vomiting. The initial evaluation in 75% was gastroenterologic. Vomiting lasted a median of 4 weeks (range, 2 days-80 weeks). Optic neuritis or transverse myelitis developed after vomiting onset in 11 patients (median interval, 11 weeks; range, 1-156). At last evaluation (median, 48 months after vomiting onset), 7 patients fulfilled neuromyelitis optica diagnostic criteria. Our clinical, pathologic and neuroimaging observations suggest the aquaporin-4-rich area postrema may be a first point of attack in neuromyelitis optica. PMID- 21031588 TI - Multiple sclerosis as an "inside-out" disease. PMID- 21031589 TI - Interleukin-6-174 CC polymorphism is associated with clinical chorioamnionitis and cerebral palsy. PMID- 21031592 TI - The challenge of causal inference. PMID- 21031593 TI - Visceral obesity and brain volume. PMID- 21031595 TI - Molybdenum cofactor deficiency: Mutations in GPHN, MOCS1, and MOCS2. AB - All molybdenum-containing enzymes other than the bacterial nitrogenase share an identical molybdenum cofactor (MoCo), which is synthesized via a conserved pathway in all organisms and therefore also is called "universal molybdenum cofactor." In humans, four molybdoenzymes are known: aldehyde oxidase, mitochondrial amidoxime reducing component (mARC), xanthine oxidoreductase, and sulfite oxidase. Mutations in the genes encoding the biosynthetic MoCo pathway enzymes abrogate the activities of all molybdoenzymes and result in the "combined" form of MoCo deficiency, which is clinically very similar to isolated sulfite oxidase deficiency, caused by mutations in the gene for the corresponding apoenzyme. Both deficiencies are inherited as an autosomal-recessive disease and result in progressive neurological damage and early childhood death in most cases. The majority of mutations leading to MoCo deficiency have been identified in the genes MOCS1 (type A deficiency), MOCS2 (type B deficiency), with one reported in GPHN. For type A deficiency an effective substitution therapy has been described recently. PMID- 21031596 TI - Genetic classification and mutational spectrum of more than 600 patients with a Zellweger syndrome spectrum disorder. AB - The autosomal recessive Zellweger syndrome spectrum (ZSS) disorders comprise a main subgroup of the peroxisome biogenesis disorders and can be caused by mutations in any of 12 different currently identified PEX genes resulting in severe multisystemic disorders. To get insight into the spectrum of PEX gene defects among ZSS disorders and to investigate if additional human PEX genes are required for functional peroxisome biogenesis, we assigned over 600 ZSS fibroblast cell lines to different genetic complementation groups. These fibroblast cell lines were subjected to a complementation assay involving fusion by means of polyethylene glycol or a PEX cDNA transfection assay specifically developed for this purpose. In a majority of the cell lines we subsequently determined the underlying mutations by sequence analysis of the implicated PEX genes. The PEX cDNA transfection assay allows for the rapid identification of PEX genes defective in ZSS patients. The assignment of over 600 fibroblast cell lines to different genetic complementation groups provides the most comprehensive and representative overview of the frequency distribution of the different PEX gene defects. We did not identify any novel genetic complementation group, suggesting that all PEX gene defects resulting in peroxisome deficiency are currently known. PMID- 21031597 TI - Dissecting loss of heterozygosity (LOH) in neurofibromatosis type 1-associated neurofibromas: Importance of copy neutral LOH. AB - Dermal neurofibromas (dNFs) are benign tumors of the peripheral nervous system typically associated with Neurofibromatosis type 1 (NF1) patients. Genes controlling the integrity of the DNA are likely to influence the number of neurofibromas developed because dNFs are caused by somatic mutational inactivation of the NF1 gene, frequently evidenced by loss of heterozygosity (LOH). We performed a comprehensive analysis of the prevalence and mechanisms of LOH in dNFs. Our study included 518 dNFs from 113 patients. LOH was detected in 25% of the dNFs (N = 129). The most frequent mechanism causing LOH was mitotic recombination, which was observed in 62% of LOH-tumors (N = 80), and which does not reduce the number of NF1 gene copies. All events were generated by a single crossover located between the centromere and the NF1 gene, resulting in isodisomy of 17q. LOH due to the loss of the NF1 gene accounted for a 38% of dNFs with LOH (N = 49), with deletions ranging in size from ~80 kb to ~8 Mb within 17q. In one tumor we identified the first example of a neurofibroma-associated second-hit type-2 NF1 deletion. Analysis of the prevalence of mechanisms causing LOH in dNFs in individual patients (possibly under genetic control) will elucidate whether there exist interindividual variation. PMID- 21031599 TI - PRO-MINE: A bioinformatics repository and analytical tool for TARDBP mutations. AB - TDP-43 is a multifunctional RNA-binding protein found to be a major protein component of intracellular inclusions found in neurodegenerative disorders such as Fronto Temporal Lobar Degeneration, Amyotrophic Lateral Sclerosis, and Alzheimer Disease. PRO-MINE (PROtein Mutations In NEurodegeneration) is a database populated with manually curated data from the literature regarding all TDP-43/TDP43/TARDBP gene disease-associated mutations identified to date. A web server interface has been developed to query the database and to provide tools for the analysis of already reported or novel TDP-43 gene mutations. As is usually the case with genetic association studies, assessing the potential impact of identified mutations is of crucial importance, and in order to avoid prediction biases it is essential to compare the prediction results. However, in most cases mutations have to be submitted separately to various prediction tools and the individual results manually merged together afterwards. The implemented web server aims to overcome the problem by providing simultaneous access to several prediction tools and by displaying the results into a single output. Furthermore, the results are displayed together in a comprehensive output for a more convenient analysis and are enriched with additional information about mutations. In addition, our web server can also display the mutation(s) of interest within an alignment of annotated TDP-43 protein sequences from different vertebrate species. In this way, the degree of sequence conservation where the mutation(s) occur can be easily tracked and visualized. The web server is freely available to researchers and can be accessed at http://bioinfo.hr/pro-mine. PMID- 21031598 TI - A novel CRYGD mutation (p.Trp43Arg) causing autosomal dominant congenital cataract in a Chinese family. AB - To identify the genetic defect associated with autosomal dominant congenital nuclear cataract in a Chinese family, molecular genetic investigation via haplotype analysis and direct sequencing were performed Sequencing of the CRYGD gene revealed a c.127T>C transition, which resulted in a substitution of a highly conserved tryptophan with arginine at codon 43 (p.Trp43Arg). This mutation co segregated with all affected individuals and was not observed in either unaffected family members or in 200 normal unrelated individuals. Biophysical studies indicated that the p.Trp43Arg mutation resulted in significant tertiary structural changes. The mutant protein was much less stable than the wild-type protein, and was more prone to aggregate when subjected to environmental stresses such as heat and UV irradiation. PMID- 21031604 TI - Determination of the conformations and relative configurations of exocyclic amines. AB - The conformations and relative configurations of 20 amines, classified according to the following labeling scheme, were analyzed. Series a comprised compounds derived from N-(1-phenylethyl)cyclohexanamine, b comprised derivatives of N-[1 (naphthalen-2-yl)ethyl]cyclohexanamine, c comprised derivatives of N (diphenylmethyl)cyclohexanamine, and d comprised derivatives of N-(propan-2 yl)cyclohexanamine. The compounds were labeled as follows: 1 indicates cyclohexanamine, 2 indicates 2-methylcyclohexanamines, 3 indicates 3 methylcyclohexanamines, 4 indicates 4-methylcyclohexanamines, and 5 indicates 4 tert-butylcyclohexanamines. These compounds were prepared without the use of stereoselective induction and, therefore, all expected stereoisomers were observed. Structural assignments were established by (1)H, (13)C, and (15)N NMR. PMID- 21031608 TI - Lateral diffusion in sphingomyelin bilayers. AB - Sphingomyelin (SM) is an important lipid of eukaryotic cellular membranes and neuronal tissues. We studied lateral diffusion in macroscopically oriented bilayers of synthetic palmitoylsphingomyelin (PSM) and natural sphingomyelins of egg yolk (eSM), bovine brain (bSM) and bovine milk (mSM) by pulsed field gradient NMR (PFG NMR) in the temperature range 45-60 degrees C. We found that the mean values of lateral diffusion coefficients (LDCs) of SMs are 1.9-fold lower compared with those of dipalmitoylphosphatidylcholine (DPPC), which is similar in molecular structure. This discrepancy could be explained by the characteristics of intermolecular SM interactions. The LDCs of different SMs differ: egg SM is most similar to PSM; both of them have a 10% higher LDC value compared with the other two natural SMs. Besides, all natural SMs show a complicated form of the spin-echo diffusion decay (DD), which is an indicator of a distribution of LDC values in bilayers. This peculiarity is explained by the broad distributions of hydrocarbon chain lengths of the natural SMs studied here, especially mSM and bSM. We confirmed the relationship between chain length and LDC in the bilayers by computer analysis of a set of (1)H NMR spectra obtained by scanning the value of the pulsed field gradient. There is a correlation between lower LDC values and SM molecules with longer acyl chains. The most probable mechanisms by which long chain SM molecules decrease their lateral diffusion relative to the average value are protrusion into the other side of the bilayer or lateral separation into areas that diverge with their LDCs. PMID- 21031612 TI - Ginsenoside Rg1 modulation on thrombospondin-1 and vascular endothelial growth factor expression in early renal fibrogenesis in unilateral obstruction. AB - Renal interstitial fibrosis is the major histopathological change seen in a variety of renal disorders and is closely related to renal dysfunction. Progressive interstitial fibrosis accompanied by the loss of renal tubules and interstitial capillaries typifies all progressive renal disease. Thrombospondin-1 (TSP-1) is a major angiogenic inhibitor. It is demonstrated that TSP-1 levels were correlated with the loss of glomerular and peritubular capillaries and TSP-1 could promote renal scarring by effects on the endothelium. It has been reported that ginsenoside Rg1 inhibited renal interstitial fibrosis in rats via suppressing the expression of TSP-1. The present study was designed to examine whether ginsenoside Rg1 could modulate the integrity of the microvasculature and hence affect the progression of renal fibrosis in a rat unilateral ureteral obstruction (UUO) model. In UUO control kidneys, associated with interstitial fibrosis, lower peritubular capillary densities were prominent. These changes were all improved by ginsenoside Rg1 treatment. Interestingly, ginsenoside Rg1 decreased the expression of TSP-1 and enhanced vascular endothelial growth factor (VEGF) expression. The results show for the first time that ginsenoside Rg1 can evidently inhibit renal interstitial fibrosis in rats with UUO. The mechanism might be related to suppression of the expression of TSP-1 and to repair of the peritubular capillary. PMID- 21031613 TI - alpha-Glucosidase inhibition and the in vivo hypoglycemic effect of butyl isobutyl-phthalate derived from the Laminaria japonica rhizoid. AB - The rhizoid of Laminaria japonica is widely used in Chinese medicine as a treatment for diabetes. Therefore, a bioactivity-tailored isolation and detailed chemical characterization was used to identify the antidiabetes compounds found in the L. japonica rhizoid. Liquid chromatography/mass spectrometry (LC/MS), proton NMR and carbon NMR spectra analyses demonstrated that the active compound was butyl-isobutyl-phthalate (BIP). BIP demonstrated a significant concentration dependent, non-competitive inhibitory activity against alpha-glucosidase in vitro, with an IC(50) of 38 MUm. In vivo, the ethyl acetate fraction (EAF) and purified BIP displayed a significant hypoglycemic effect in streptozocin-induced diabetic mice. The present study indicates BIP could be considered as an alpha glucosidase inhibitor and developed as an important antidiabetes agent for type II diabetes therapy. PMID- 21031614 TI - Extract of Chaga mushroom (Inonotus obliquus) stimulates 3T3-L1 adipocyte differentiation. AB - Chaga mushroom (Inonotus obliquus) has long been used as a folk medicine due to its numerous biological functions such as antibacterial, antiallergic, antiinflammatory and antioxidative activities. In the present study, it was found that the I. obliquus hot water extract (IOWE) activated adipogenesis of 3T3-L1 preadipocytes. Even in the absence of adipogenic stimuli by insulin, the IOWE strongly induced adipogenesis of 3T3-L1 preadipocytes. The major constituent of IOWE was glucose-rich polysaccharides with a molecular mass of 149 kDa. IOWE enhanced the differentiation of 3T3-L1 preadipocytes, increasing TG (triacylglycerol) accumulation that is critical for acquisition of the adipocyte phenotype, in a dose-dependent manner. IOWE stimulated gene expression of C/EBPalpha (CCAAT/enhancer-binding protein alpha) and PPARgamma (peroxisome proliferator-activated receptors gamma) during adipocyte differentiation, and induced the expression of PPARgamma target genes such as aP2 (adipocyte protein 2), LPL (lipoprotein lipase) and CD36 (fatty acid translocase). Immunoblot analysis revealed that IOWE increased the expression of adipogenic makers such as PPARgamma and GLUT4 (glucose transporter 4). The luciferase reporter assay demonstrated that IOWE did not exhibit PPARgamma ligand activity. Although these results require further investigation, the ability of natural mushroom product to increase PPARgamma transcriptional activities may be expected to be therapeutic targets for dyslipidemia and type 2 diabetes. PMID- 21031615 TI - Inhibitory effect of panduratin A isolated from Kaempferia panduarata Roxb. on melanin biosynthesis. AB - Hyperpigmentation disorders are associated with abnormal accumulation of melanin pigments, thus melanin synthesis inhibitors have been of great interest as target molecules for cosmetic and medicinal purposes. The aim of this study was to investigate the in vitro inhibitory effect of panduratin A, isolated from Kaempferia pandurata Roxb., on melanogenesis and its related enzymes such as tyrosinase, tyrosinase related protein-1 (TRP-1) and tyrosinase related protein-2 (TRP-2) in melan-a murine melanocytes. The IC(50) values of panduratin A for melanogenesis and tyrosinase were 9.6 MUm and 8.2 MUm, respectively, while those of arbutin as a positive control were 990 MUm and 660 MUm, respectively. In western blot analysis, panduratin A also significantly decreased tyrosinase, TRP 1 and TRP-2 protein levels. These results indicate that panduratin A effectively inhibits melanin biosynthesis, thus creating the possibility of developing a new skin-whitening agent. PMID- 21031616 TI - The effect of Echinacea preparations in three laboratory tests of anxiety: comparison with chlordiazepoxide. AB - Echinacea preparations are traditionally used to treat upper respiratory infections and inflammations. No psychotropic effects of Echinacea have been reported so far, although some recently reported active constituents are behaviorally active. Prompted by these findings, the anxiolytic potential of five different Echinacea preparations was evaluated. Three of these decreased anxiety but two of them had a very narrow effective dose range. Only one extract decreased anxiety within a wide dose-range (3-8 mg/kg). Anxiolytic effects were consistently seen in three different tests of anxiety, the elevated plus-maze, social interaction and shock-induced social avoidance tests. No locomotor suppressant effects were seen at any dose. Noteworthy, the doses that showed anxiolytic effects in the present study were much lower than those used in the laboratory models of the traditional indications. Chlordiazepoxide robustly decreased anxiety-like behavior in all tests but suppressed locomotion at higher doses. Perceived and real risks of conventional medications increase the demand for alternative therapies, provided that these are safe and efficient. Earlier evidence shows that Echinacea preparations have an excellent safety profile, while our findings suggest for the first time that certain preparations have a considerable anxiolytic potential. Further research is required to identify factors that differentiate efficient and inefficient preparations. PMID- 21031617 TI - The ability of green tea to positively modulate key markers of gastrointestinal function in rats. AB - The beneficial effects of selenium-containing green tea (Se-GTE, 1.44 mg selenium/kg dry leaves) and China green tea (CH-GTE, 0.13 mg selenium/kg leaves) on the population size of lactobacilli and bifidobacteria and the activity of two microbial enzymes in the caeca of rats have been investigated. Oral gavage of rats with Se-GTE extract for 6 days resulted in a significant increase in caecal counts of lactobacilli and bifidobacteria (p < 0.05) while significantly reducing the caecal counts of bacteroides and clostridial bacteria. In contrast, gavaging the rats with CH-GTE extract for 6 days resulted in a slight but not significant increase in the numbers of caecal lactobacilli and bifidobacteria but decreased significantly the numbers of bacteroides (p < 0.05) and clostridia (p < 0.05). In addition, rats gavaged with CH-GTE and Se-GTE showed a 17.2% and 21.3% reduction in the activity of the bacterial enzyme beta-glucuronidase, respectively, when compared with the rats gavaged with water only. beta-glucuronidase is considered to be one of the enzymes that increases the risk for colorectal cancer. Moreover, gavaging rats with these teas resulted in 19% and 25.5% increments in the activity of beta-glucosidase, respectively. In conclusion, Se-GTE showed both bifidogenic and lactogenic effects and the high level of selenium may be behind the superiority of this tea over CH-GTE. PMID- 21031618 TI - Acute effects of dietary ginger on muscle pain induced by eccentric exercise. AB - Zingiber officinale, commonly known as ginger, has analgesic and antiinflammatory properties. The acute effects of ginger on muscle pain, inflammation and dysfunction induced by eccentric exercise were examined. Twenty-seven participants performed 24 eccentric actions of the non-dominant elbow flexors. In a double-blind, cross-over design, participants ingested a 2 g dose of ginger or placebo 24 h and 48 h after exercise. Pain intensity (0-100 mm), arm volume (water displacement), range-of-motion (goniometry) and metabolic rate were assessed before and 45 min after ingestion of ginger or placebo. Eccentric exercise induced moderate arm pain (39 +/- 20 mm; mean +/- SD) and dysfunction (14% decrease in ROM) and an increase in volume (1.8%). Overall, ginger consumption demonstrated no effect on muscle pain, dysfunction, or metabolic rate compared with placebo. In the sub-set of participants who consumed ginger 24 h after exercise, arm pain was reduced (13%, -5.9 +/- 8.8 mm) the following day, 48 h after exercise. Participants who ingested placebo 24 h post-exercise exhibited no change in pain the following day (0.0 +/- 14.7 mm). In conclusion, a single 2 g dose of ginger does not attenuate eccentric exercise-induced muscle pain, inflammation or dysfunction 45 min after ingestion. However, ginger may attenuate the day-to-day progression of muscle pain. PMID- 21031619 TI - In vitro antiviral activity of lutein against hepatitis B virus. AB - Despite the availability of an effective vaccine, the hepatitis B virus (HBV) infection and its treatment remains one of the foremost public health problems in the world. The present study was performed in order to investigate the anti-HBV activity of lutein in vitro. The antiviral activity of lutein was examined by detecting the levels of HBsAg, HBeAg and extracellular HBV DNA in stable HBV producing human hepatoblastoma HepG2 2.2.15 cells. It was found that lutein effectively suppressed the secretion of HBsAg from HepG2 2.2.15 cells in a dose dependent manner, and it also suppressed the amount of extracellular HBV DNA. A luciferase reporter gene assay was used to determine the effects of lutein on the activities of HBV promoters. The results showed that lutein inhibited the activity of HBV full-length promoter (Fp). These data indicate that lutein possesses an anti-HBV activity and exerts its antivirus effects via inhibition of HBV transcription. PMID- 21031620 TI - Immunomodulatory response of Cramoll 1,4 lectin on experimental lymphocytes. AB - Cramoll 1,4 is a lectin extracted from Cratylia mollis Mart. seeds that has shown antitumor and lymphocyte mitogenic activities in other studies. The aim of this work was to investigate, in vitro, the immunomodulatory activity of Cramoll 1,4 on experimental cultures of mice lymphocytes through cytotoxic assays, nitric oxide (NO) concentrations and IL-10 and IFN-gamma production. Cramoll 1,4 did not show cytotoxic activity at 1-25 MUg/mL concentrations, similar results were observed with concanavalin A (Con A) and phytohemagglutinin (PHA) lectins. The minimum production of IL-10 was observed in splenocytes cultivated with Con A, PHA and Cramoll 1,4 lectins. However, splenocytes treated with Cramoll 1,4 showed higher IFN-gamma production in comparison with PHA and Con A (p < 0.05 for both). Production of NO was effectively suppressed in murine cells stimulated with the lectins and was only detected after 72 h for PHA in relation to non-stimulated lymphocytes (p < 0.05). Cramoll 1,4 was not toxic to murine lymphocytes, induced Th1 response through IFN-gamma production and showed antiinflammatory activity through NO suppression. Therefore, Cramoll 1,4 can be considered a lectin with immunomodulatory activity. PMID- 21031621 TI - Antiproliferative effect of resveratrol in pancreatic cancer cells. AB - To investigate resveratrol, one of the food derived polyphenols that might be partially responsible for the beneficial effect on cancer, the in vitro antitumor activity of resveratrol against pancreatic cancer cell lines (PANC-1, BxPC-3 and AsPC-1) was examined, together with the mechanisms involved. The effects of resveratrol on the growth inhibition, apoptosis and cell cycle were assayed. The activity of caspases and the expression of Bcl-2, Bcl-xL, XIAP and Bax protein were detected. The results showed that resveratrol inhibited the proliferation of pancreatic cancer cells in a dose- and time-dependent manner. Resveratrol inhibited the cell growth of PANC-1, BxPC-3 and AsPC-1 cells with IC(50) values of 78.3 +/- 9.6 MUmol/L, 76.1 +/- 7.8 MUmol/L and 123.1 +/- 6.5 MUmol/L at 48 h, respectively. Incubation of pancreatic cancer cells with resveratrol resulted in cell apoptosis and cell cycle arrests. Resveratrol induced activation of caspases. Simultaneously, resveratrol regulated the expression of the antiapoptotic proteins Bcl-2, Bcl-xL and XIAP and the proapoptotic protein Bax. PANC-1 and BxPC-3 cells were more chemosensitive to resveratrol than AsPC-1 cells. In conclusion, resveratrol inhibited the proliferation of pancreatic cancer cells by inducing apoptotic cell death. There was different sensitivity to resveratrol in different pancreatic cancer cell lines. PMID- 21031622 TI - Intrathecal eugenol administration alleviates neuropathic pain in male Sprague Dawley rats. AB - The main objective of this study was to determine the central effect of eugenol on neuropathic pain when injected intrathecally at the level of the lumbar spinal cord. In a preliminary study the penetrability of eugenol was evaluated in the CNS of rats. Blood, brain and spinal cord samples were collected at selected time points following eugenol administration and concentrations were determined by tandem liquid chromatography-mass spectrometry. Brain-to-plasma and spinal cord to-plasma ratios (3.3 and 6.7, respectively) suggest that eugenol penetrates relatively well the CNS of rats, with a preferential distribution in the spinal cord. Following the induction of neuropathic pain in rats using the sciatic nerve ligation model, intrathecal injections of eugenol were done to evaluate the central effect of eugenol. Treatment with 50 MUg of eugenol significantly decreased secondary mechanical allodynia after 15 min, 2 h and 4 h (p < 0.05; <0.005; <0.05, respectively) and improved thermal hyperalgesia after 2 h and 4 h (p < 0.001 and p < 0.05). The results support the hypothesis that eugenol may alleviate neuropathic pain, both allodynia and hyperalgesia, by acting centrally most probably at the level of the dorsal horn of the spinal cord where vanilloid receptors can be found. PMID- 21031623 TI - Effect of silymarin administration on TNF-alpha serum concentration in peritoneal dialysis patients. AB - Chronic inflammation in dialysis patients increases the production of cytokines such as TNF-alpha, IL-1beta and IFN- IFN-gamma and there is evidence of a significant mortality rate in dialysis patients due to inflammation. Overproduction of inflammatory cytokines can induce complications such as atherosclerosis, malnutrition and anaemia, which are mostly resistant to erythropoietin treatment. Cardiovascular disease is the leading cause of death in haemodialysis patients and about half of the mortality is attributable to cardiovascular disease. Silymarin modulates the immune system by inhibition of neutrophil immigration, mast cell immobilization, prostaglandin production and leukotriene synthesis. Furthermore, silymarin suppresses the induction of TNF alpha and it was hypothesized that silymarin could decrease the serum concentration of TNF-alpha in peritoneal dialysis patients, and thus treat anaemia. Fifteen peritoneal dialysis patients were enrolled in this study and serum levels of soluble TNF-alpha were measured using an enzyme-linked immunosorbant assay (ELISA) kit. Serum TNF-alpha was found to be decreased in some patients and in the response group, the haemoglobin concentration after 8 weeks of silymarin administration was increased significantly (p < 0.05). Based on the results of this study, it is suggested that silymarin may be useful in the treatment of inflammation for peritoneal dialysis patients. PMID- 21031624 TI - Icariin improves memory impairment in Alzheimer's disease model mice (5xFAD) and attenuates amyloid beta-induced neurite atrophy. AB - Essential therapeutic drugs for Alzheimer's disease (AD) have not been developed. Since the neuritic atrophy leading to synaptic losses is one of the critical causes of memory impairment in AD, the effects of several constituents in tonic herbal medicines on neuritic atrophy and memory deficits have been studied. The present study investigated the effects of icariin, a main constituent in Epimedii Herba, a well known tonic crude drug, in an in vitro AD model and transgenic mouse AD model (5xFAD). Amyloid beta(1-42)-induced atrophies of axons and dendrites were restored by post-treatment with icariin in rat cortical neurons. Administration of icariin for 8 days (p.o.) improved spatial memory impairment in 5xFAD mice. These novel findings suggest that icariin may improve memory dysfunction in AD and have a potential to extend neurites even when amyloid beta induced neurite atrophy has already occurred. PMID- 21031625 TI - Bioactivity-guided isolation of antiproliferative compounds from Centaurea arenaria. AB - The antiproliferative effects of n-hexane, chloroform and aqueous methanol extracts prepared from the whole plant of Centaurea arenaria M.B. ex Willd. were investigated against cervix adenocarcinoma (HeLa), breast adenocarcinoma (MCF7) and skin epidermoid carcinoma (A431) cells, using the MTT assay. The chloroform extract displayed high tumour cell proliferation inhibitory activity (higher than 85% at 10 MUg/mL concentration), and was therefore subjected to a bioassay-guided multistep separation procedure. Flavonoids (eupatilin, eupatorin, 3' methyleupatorin, apigenin and isokaempferid), lignans (arctigenin, arctiin and matairesinol), the sesquiterpene cnicin, serotonin conjugates (moschamine and cis moschamine), beta-amyrin and beta-sitosterin-beta-D-glycopyranoside, identified by means of UV, MS and NMR spectroscopy, were obtained for the first time from this species. The isolated compounds were also evaluated for their tumour cell growth inhibitory activities on HeLa, MCF7 and A431 cells, and different types of secondary metabolites were found to be responsible for the antitumour effects of the extracts; in addition to moderately active compounds (isokaempferid and moschamine), especially apigenin, eupatorin, arctigenin, arctiin, matairesinol and cnicin exert marked antitumour effects against these cell lines. PMID- 21031626 TI - Reversible inhibition of three important human liver cytochrome p450 enzymes by tiliroside. AB - Tiliroside, an active flavonoid extensively found in many medicinal plants including Helichrysum italicum, Geranium mexicanum and Helianthemum glomeratum, has been demonstrated to exert multiple biological effects including antiinflammatory, antimicrobial, antioxidant and antitumor activities. Cytochrome P450 (CYP) enzymes play an important role in the Phase I oxidation metabolism of a wide range of xenobiotics and inhibition of CYP isoforms might influence the elimination of drugs and induce serious adverse drug response. The inhibition of seven CYP isoforms (CYP3A4, CYP1A2, CYP2A6, CYP2D6, CYP2C9, CYP2C8 and CYP2E1) by tiliroside was investigated using in vitro human liver microsomal incubation assays. The results showed that tiliroside strongly inhibited the activity of CYP3A4 (IC(50) = 9.0 +/- 1.7 MUm), CYP2C8 (IC(50) = 12.1 +/- 0.9 MUm) and CYP2C9 (IC(50) = 10.2 +/- 0.9 MUm) with other CYP isoforms negligibly influenced. Further kinetic analysis showed that inhibition of these three CYP isoforms by tiliroside is best fit to a competitive way. The K(i) value was calculated to be 5.5 MUm, 3.3 MUm, 9.4 MUm for CYP3A4, CYP2C9 and CYP2C8, respectively. The relatively low K(i) values suggested that tiliroside might induce drug-drug interactions with many clinically used drugs which are mainly metabolized by these three CYP isoforms. Therefore, attention should be given to the probable drug-drug interaction between tiliroside-containing herbs and substrates of CYP3A4, CYP2C9 and CYP2C8. PMID- 21031627 TI - Antimalarial activity of extract and norbergenin derivatives from the stem bark of Diospyros sanza-minika A. Chevalier (Ebenaceae). AB - The methanol extract from the stem bark of Diospyros sanza-minika as well as five norbergenin derivatives isolated from this crude extract were evaluated for their in vitro activity against Plasmodium falciparum K1 and cytotoxicity on MRC-5 cells. 4-O-(3'-methylgalloyl)norbergenin was found to be the most potent compound (IC(50) 0.6 MUg/mL; CC(50) 24.7 MUg/mL), followed by 4-O-galloylnorbergenin (IC(50) 3.9 MUg/mL; CC(50) > 64 MUg/mL) and 11-O-p-hydroxy-benzoyl-norbergenin (IC(50) 4.9 MUg/mL; CC(50) > 64 MUg/mL). Norbergenin and 4-O-syringoylnorbergenin were inactive (IC(50) > 32 MUg/mL; CC(50) > 64 MUg/mL). The antimalarial activity of the pure constituents and of the methanol extract from the stem bark of Diospyros sanza-minika is reported for the first time. The results provide interesting baseline information for the potential use of the crude extract well as some of the isolated compounds in the search for novel antimalarial compounds. PMID- 21031628 TI - Protein kinase C pathway is involved in the inhibition by crocetin of vascular smooth muscle cells proliferation. AB - Crocetin is a natural carotenoid compound isolated from Gardenia jasminoids Ellis. Our previous study showed that crocetin inhibits angiotensin II (Ang II) induced proliferation of vascular smooth muscle cells (VSMCs). The present study investigated the involvement of the protein kinase C (PKC) pathway in the growth inhibitory action of crocetin in VSMCs. The findings showed that PKC activity in the membrane fraction of VSMCs increased following stimulation with Ang II, which was suppressed significantly by pretreating the cells with crocetin. Inhibition of PKC activity by crocetin appeared to be associated with growth inhibition in VSMCs, because chelerythrine chloride, a specific PKC inhibitor, likewise decreased cell proliferation. PKC-a, a conventional PKC isoform, was detected in bovine aorta VSMCs by RT-PCR and western blotting analysis. Crocetin inhibited Ang II-induced membrane translocation of PKC-a, and the inhibition of crocetin on PKC activity in membrane fraction coincided with its suppression on membrane translocation of PKC-a. In addition, Ang II-induced mRNA expressions of c-fos, c jun and c-myc were also decreased by crocetin. Taken together, the data suggest that the inhibition by crocetin of PKC activity, at least in part due to inactivation of PKC-a, and the subsequent suppression of proto-oncogene expressions might mediate its inhibitory effect on VSMCs proliferation. PMID- 21031630 TI - Radioprotective activity of Gentiana lutea extract and mangiferin. AB - Radioprotective/sensitizing actions of Gentiana lutea aqueous-ethanol extract and mangiferin on radiation-induced effects on different types of cells were investigated. The study focused on the decreasing survival of normal human immunocompetent cells, the survival of the malignant cells in vitro, and the survival of ex vivo irradiated cells before and after consumption of the extract by healthy volunteers. The in vitro experiments showed that mangiferin could inhibit cytotoxic action of ionizing irradiation (doses of 6 and 8 Gy) only on normal resting human PBMC, not stimulated for proliferation. Orally consumed G. lutea extract showed the potential to reduce the cytotoxic effect of x-ray irradiation on normal human immunocompetent cells PBMC of some healthy people, without changing the susceptibility of malignant cells to be destroyed by irradiation. Since the radioprotective effect was individually dependent, further clinical studies are needed. PMID- 21031629 TI - Active principles of Grindelia robusta exert antiinflammatory properties in a macrophage model. AB - Plant extracts and/or secondary metabolites are receiving considerable attention as therapeutic agents for treating inflammatory diseases such as periodontitis, which affects the tooth supporting tissues. The aim of this study was to investigate the effect of a Grindelia robusta extract enriched in saponins and polyphenols on Aggregatibacter actinomycetemcomitans lipopolysaccharide (LPS) induced inflammatory mediator (IL-6, TNF-a, RANTES, MCP-1, PGE(2) ) and matrix metalloproteinase (MMP-1, -3, -7, -8, -9, -13) secretion by macrophages. LPS induced a marked increase in the secretion of all inflammatory mediators and MMPs tested by macrophages, as determined by enzyme-linked immunosorbent assays. At non-cytotoxic concentrations, the G. robusta extract inhibited dose-dependently the secretion of IL-6, RANTES, MCP-1 and, to a lesser extent, PGE(2) and TNF-a. Such inhibition was also observed for MMP-1, -3, -7, -8, -9 and -13 secretion. This ability of G. robusta extract to reduce the LPS-induced secretion of inflammatory mediators and MMPs was associated with a reduction of nuclear factor kappa B (NF-kB) p65 activation. The results suggest that G. robusta extract possesses an antiinflammatory therapeutic potential through its capacity to reduce the accumulation of inflammatory mediators and MMPs. PMID- 21031631 TI - Antiinflammatory activity of coumarins from Ligusticum lucidum Mill. subsp. cuneifolium (Guss.) Tammaro (Apiaceae). AB - Four coumarin derivatives [selidinin 1, (+)-praeruptorin A 2, visnadin 3 and (R) (+)-7-(2',3'-epoxy-3'-methylbutoxy)-coumarin 4] were isolated from the aerial parts of Ligusticum lucidum Mill. subsp. cuneifolium (Guss.) Tammaro (Apiaceae). This is the first report on the identification of these compounds in the Ligusticum genus. Their topical antiinflammatory activity was evaluated as the inhibition of croton oil-induced ear dermatitis in mice. Each compound (0.3 MUmol/cm(2) ) induced a significant oedema reduction and compound 4 exerted an effect similar to that of the equimolar dose of the reference drug indomethacin. PMID- 21031632 TI - Traditional medicine Taeeumjowitangkagambang exerts antiobesity and hypolipidemic effects via antioxidant enzyme enhancement. AB - Taeeumjowitangkagambang (ETJKB) is a traditional Korean medicine that has been clinically used for obesity with little mechanistic understanding. The present study investigated antiobesity and hypolipidemic effects of ETJKB in high fat diet fed rats as well as a 3T3-L1 pre-adipocyte differentiation model. ETJKB significantly inhibited the lipidogenesis in 3T3-L1 adipocytes in a concentration dependent manner as well as reduced the cellular adipokine leptin level. Daily oral gavage of ETJKB to rats fed a high fat diet significantly attenuated body weight gain and abdominal and epididymal fat weights. ETJKB treatment also reduced the levels of total cholesterol, low density lipoprotein (LDL) and triglyceride as well as increased high density lipoprotein (HDL) in serum compared with the untreated control. Similarly, the ETJKB treatment decreased the levels of total lipid, triglyceride and cholesterol in liver tissue in high fat diet fed rats. Interestingly, ETJKB significantly increased the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase in liver tissue, while decreasing the hydroxyl radical, thiobarbituric acid reactive substances (TBARS), carbonyl concentration. An improvement of antioxidant enzymes was associated with improved body weight control and healthier lipid profiles and therefore may play an important role in the antiobesity and hypolipidemic effects of ETJKB. PMID- 21031633 TI - Biologically active sesquiterpene coumarins from Ferula species. AB - Extracts from different species of the genus Ferula (Apiaceae) have had various biomedical applications for many centuries. Many biological features of this genus such as cytotoxicity, antibacterial, antiviral, P-glycoprotein (P-gp) inhibitory and antiinflammatory activity have been attributed to sesquiterpene coumarins; structures containing a common coumarin group and a sesquiterpene moiety. This both highlights the importance of sesquiterpene coumarins as biologically active natural products and necessitates further studies on these compounds. Taking into account the versatile biological properties of compounds isolated from Ferula and the unprecedented interest in the application of natural products as a new generation of therapeutics, the present review will discuss reports on biological activities of sesquiterpene coumarins of the genus Ferula, from 1990 onwards. PMID- 21031634 TI - Comparative investigations on the protective effects of rhodioside, ciwujianoside B and astragaloside IV on radiation injuries of the hematopoietic system in mice. AB - The aim of this study was to investigate the protective effects of three glycosides (rhodioside, ciwujianoside-B and astragaloside IV) on the hematopoietic system in the mice exposed to gamma-rays, and to examine the possible mechanisms involved. Mice were pretreated with the glycosides (40 mg/kg, i.g.) daily for 7 days prior to radiation. The survival of mice pretreated with three glycosides after total body irradiation (6.0 Gy) was examined. Peripheral blood leucocytes and endogenous spleen colony counts, colony-forming unit granulocyte macrophage assay, analysis of DNA content and apoptosis rate determination were performed to evaluate the effects of the three glycosides on hematogenesis. The fragmentation of double-stranded DNA in lymphocytes was detected by the comet assay. The changes in cell cycle were analysed by flow cytometry. Furthermore, the expression levels of Bcl-2, Bax and nuclear factor kappa B (NF-kappaB) were measured by western blot and the electrophoretic mobility shift assay. The results showed that pretreatment with all of the glycosides improved survival time and increased the number of leucocytes, spleen colonies and granulocyte-macrophage colonies in mice exposed to 6.0 Gy gamma radiation. Rhodioside showed more protective efficacy than both ciwujianoside-B and astragaloside IV. All three glycosides significantly increased the proliferation abilities of bone marrow cells, and decreased the ratio of cells in G(0)/G(1) phase. Further analysis showed that these three glycosides were able to decrease DNA damage and the increment in the Bax/Bcl-2 ratio induced by radiation. In summary, the three glycosides showed radioprotective effects on the hematopoietic system in mice, which was associated with changes in the cell cycle, a reduction in DNA damage, and down-regulation of the ratio of Bax/Bcl-2 in bone marrow cells exposed to radiation. PMID- 21031636 TI - Intimacy processes and psychological distress among couples coping with head and neck or lung cancers. PMID- 21031635 TI - Effects of coumestrol administration to pregnant and lactating mice on intestinal alkaline phosphatase activity. AB - The present study was conducted to clarify the effects of coumestrol administration on Ca metabolism during pregnancy and in lactating mice. From 6.5 to 16.5 days post coitus (dpc), pregnant mice were administered coumestrol at 200 ug/kg body weight/day. The duodenum, jejunum and blood samples were obtained at 17.5 dpc or 10 days after parturition (dap). Coumestrol administration decreased alkaline phosphatase (ALP) activity and mRNA expression of IAP and estrogen responsive genes, c-fos and vascular endothelial growth factor (VEGF), in the duodenum and jejunum of pre-delivery mice. In lactating mice, the ALP activity and mRNA expression of IAP were not changed, although coumestrol administration decreased mRNA expression of c-fos in the duodeum and VEGF in the jejunum. Coumestrol did not affect serum Ca and the expression of vitamin D receptor protein in the duodenum and jejunum. Thus, coumestrol administration during pregnancy may decrease the mRNA expression of IAP and the ALP activity in the intestine of the pre-delivery mice through ERalpha, but coumestrol had little effect on intestinal ALP activity at 10 days after parturition. PMID- 21031637 TI - Joint crepitus--are we failing our patients? PMID- 21031639 TI - Hepatic Cirrhosis in Children: With special reference to the Biliary Forms. PMID- 21031640 TI - Adrenalin in Severe Rheumatic Heart Block. PMID- 21031641 TI - Remarks on the Deformity of Pes Cavus. PMID- 21031643 TI - A Note on the Clinical Diagnosis of Rickets in Infancy. PMID- 21031642 TI - The Incidence of Rickets in a London Hospital Out-patient Department. PMID- 21031644 TI - A Study of Rickets; Incidence in London. PMID- 21031645 TI - Recent Advances in the Diagnosis and Treatment of Purpura Haemorrhagica. PMID- 21031646 TI - Ketonuria and Urinary Acidity. PMID- 21031648 TI - Notes on Measures in Infant Feeding. PMID- 21031647 TI - Four Cases of Immuno-Transfusion with remarks on the Method. PMID- 21031649 TI - Nephritis in Children and its Prognosis. PMID- 21031651 TI - An Investigation of Sclerema Neonatorum; with Special Reference to the Chemistry of the Subcutaneous Tissues: (Part I.). PMID- 21031650 TI - Current Problems in the Tuberculosis of Childhood: Infection, Diathesis, Artificial Pneumothorax, Preventive Inoculation. PMID- 21031652 TI - The Special Schools of London. PMID- 21031654 TI - The Remote Prognosis of Empyema in Children. PMID- 21031653 TI - Lambliasis as a Cause of Chronic Enteritis in Children. PMID- 21031656 TI - Nephritis in Childhood. PMID- 21031655 TI - An Investigation of Sclerema Neonatorum; with Special Reference to the Chemistry of the Subcutaneous Tissues: (Part II.). PMID- 21031657 TI - A Case of Hypertelorism. PMID- 21031658 TI - A Case of Hypertelorism Without Mental Defect. PMID- 21031659 TI - Chronic Ulcerative Colitis in Children. PMID- 21031660 TI - Congenital Absence of Tibia. PMID- 21031661 TI - Scholastic and Intelligence Tests. PMID- 21031662 TI - A Study of Gastric Acidity in Infants. PMID- 21031663 TI - Calcium Absorption in Relation to Gastric Acidity: (A Study of Rickets). PMID- 21031665 TI - A Contribution to the Study of the Causation of Foetal Death. PMID- 21031664 TI - Observations on the Rheumatic Nodule. PMID- 21031666 TI - Congenital Atresia of the Alimentary Tract. PMID- 21031667 TI - Congenital Duodenal Stenosis Due to Peritoneal Bands. PMID- 21031668 TI - The Day-and-Night Creatinine and Creatine in the Urine of Infants. PMID- 21031669 TI - Tuberculous Dactylitis in Infancy. PMID- 21031671 TI - Acute Invagination of the Intestine in Small Children. PMID- 21031670 TI - Ketonaemia and Ketonuria in Childhood. PMID- 21031672 TI - Effects of Scarlet Fever on Rheumatic Subjects. PMID- 21031673 TI - Some Experiments with Haemolytic Streptococcus Toxin of Varying Origin in Connection with the "Dick" Test for Scarlet Fever. PMID- 21031674 TI - The Creatinine Coefficient in the Infant. PMID- 21031675 TI - Effect of Encephalitis Lethargica on the Intelligence of Children. PMID- 21031677 TI - The Bone Changes Occurring in Renal and Coeliac Infantilism, and Their Relationship to Rickets: Part I. Renal Rickets. PMID- 21031676 TI - The Relation of Hypertelorism to Mongolism: With Description of a Case. PMID- 21031678 TI - The Infantile Factor in Failure of Breast Feeding. PMID- 21031679 TI - Cholaemia: A Clinical Study of the Nervous Symptoms in Liver Atrophy. PMID- 21031680 TI - The Use of Banana Pulp in the Feeding of Marasmic Infants. PMID- 21031681 TI - Ketonaemia, Cyclical Vomiting and Some Nervous Disturbances in Children. PMID- 21031682 TI - Some Inspiring Cases of Acute Rheumatism. PMID- 21031683 TI - Leukaemia in Infancy and Early Life. PMID- 21031684 TI - The Indirect Determination of the pH of the Blood in Children. PMID- 21031685 TI - Bronchiectasis in Childhood: Its Symptomatology, Course and Cause. PMID- 21031686 TI - Pyelitis in Infancy; A Pathological Study. PMID- 21031687 TI - Scaphocephaly, Oxycephaly and Hypertelorism: With Reports of Cases. PMID- 21031688 TI - Observations on the Manifestations of Rickets in Liverpool. PMID- 21031689 TI - A Substitute for Buttermilk in the Treatment of Digestive Disorders During Infancy. PMID- 21031690 TI - The Dick Test in relation to the presence of the Streptococcus Haemolyticus in the Throats of Individuals not suffering from Scarlet Fever. PMID- 21031692 TI - Notes on a Case of Chronic Polyarthritis (Still's Disease) treated by Intravenous Protein Therapy. PMID- 21031691 TI - The Dreyer and Ward Sigma Reaction in Congenital Syphilis. PMID- 21031693 TI - An Analysis of One Hundred Cases of Fits in Children. PMID- 21031695 TI - A Note on Gluteal Wasting as a Sign of Coeliac Disease. PMID- 21031694 TI - A Case of Congenital Atresia of the Jejunum (with Recovery). PMID- 21031696 TI - Contribution to the Study of the Autonomic Nervous System in Children. PMID- 21031698 TI - Observations on the Action of Acetone. PMID- 21031697 TI - The Bone Changes Occurring in Renal and Coeliac Infantilism and their Relationship to Rickets: Part II. Coeliac Rickets. PMID- 21031699 TI - A Clinical, Pathological and Biochemical Study of Amyloid Nephrosis. PMID- 21031700 TI - Artificial Light Therapy in Infancy: A Comparison of 66 Cases Treated with the Mercury Vapour Quartz Lamp and 137 Control Cases. PMID- 21031701 TI - On Dilatation of the Bladder and Ureters in Childhood. PMID- 21031702 TI - Gaucher's Disease; A Clinical and Pathological Study. PMID- 21031703 TI - A Study of Phosphorus Absorption in Normal and Rachitic Children. PMID- 21031704 TI - The Function of Breast Feeding. PMID- 21031705 TI - The Frequent Occurrence of Underfeeding in Early Infancy. PMID- 21031706 TI - On the Clinical Value of Blood Analyses in Nephritis in Childhood. PMID- 21031707 TI - An Investigation Into the Incidence of Hernia in Children. PMID- 21031708 TI - Periostitis of the Metatarsus. PMID- 21031709 TI - Faecal Fat Analyses in Children. PMID- 21031710 TI - Sclerema Neonatorum and its Relation to Fat Necrosis. PMID- 21031712 TI - Hypertelorism in Several Generations. PMID- 21031711 TI - Oesophagectasia in a Child. PMID- 21031713 TI - Non-Tuberculous Fibrosis of the Lung in Children. PMID- 21031714 TI - A Study of the Distribution of Rheumatic Infection in Children in Birmingham. PMID- 21031715 TI - A Review of 180 Children Suffering from Rheumatism, Chorea and Carditis. PMID- 21031716 TI - Haemorrhagic Disease of the Newborn. PMID- 21031717 TI - A Study of two Types of Vomiting Associated with Acetonuria. PMID- 21031718 TI - Transplantation of Ureters for Congenital Incontinence: A Final Result. PMID- 21031719 TI - Analysis of the Blood Groups of Children and Infants. PMID- 21031720 TI - The Life History of Epidemic Encephalitis in the Child. PMID- 21031721 TI - Hepatic Efficiency: The Value of the Haemoclastic and the Laevulose Tests in Childhood. PMID- 21031722 TI - The Normal Cerebro-Spinal Fluid in Children. PMID- 21031723 TI - Anaemia in Infancy: Its Prevalence and Prevention. PMID- 21031725 TI - Peptic Ulcer in the New-Born. PMID- 21031724 TI - The Association of Pneumonia and Acute Bright's Disease. PMID- 21031726 TI - Duodenal Ulcers in Two Infants of the Same Family. PMID- 21031727 TI - Hypertelorism: An Unilateral Case. PMID- 21031728 TI - The Laevulose Tolerance of Con Valescent Children: With Special Reference to Rheumatism. PMID- 21031729 TI - Coarctation of the Aorta with Ulcerative Aortitis. PMID- 21031731 TI - Arsenic in the Treatment of Chorea. PMID- 21031730 TI - On Lobular and Lobar Pneumonia in Infancy and Childhood. PMID- 21031732 TI - On the AEtiology of Hirsch-Sprung's Disease. PMID- 21031734 TI - Heart Block Associated with Congenital Malformation of the Heart. PMID- 21031733 TI - Heart Block Associated with Congenital Heart Disease. PMID- 21031735 TI - The Influence of Heredity in Exophthalmic Goitre. PMID- 21031736 TI - On Pyelitis Complicated by Jaundice. PMID- 21031737 TI - A Case of Paratyphoid B. Infection with Purpura and Specific Broncho-Pneumonia. PMID- 21031738 TI - Observations on the Chloride, Sugar, and Calcium Contents of the Cerebro-Spinal Fluid in Children. PMID- 21031739 TI - The AEtiology of Coeliac Disease: Preliminary Communication on the Blood Fat. PMID- 21031740 TI - Functional Vomiting in Newborn and Premature Infants. PMID- 21031741 TI - Heart Disease in Children Attending School. PMID- 21031742 TI - A Case of Leontiasis Ossea (Diffuse Osteitic Form). PMID- 21031743 TI - Poisoning by "Meta Fuel" Tablets (Metacetaldehyde). PMID- 21031744 TI - Extreme Hypersensitiveness to Cow's Milk Protein in an Infant. PMID- 21031746 TI - Defective Children and Special Day Schools. PMID- 21031745 TI - Hemi-Hypertrophie Alterne. PMID- 21031747 TI - A Syndrome in the Rat Resembling Pink Disease in Man. PMID- 21031748 TI - Studies of Pneumonia in Childhood: I. Statistical Analysis of Pneumonia and Bronchitis. PMID- 21031749 TI - Racial Variation in Relation to Infant Mortality in the Four Principal Scottish Towns. PMID- 21031750 TI - Study of Ultra-Violet Radiation in the Treatment of Tuberculosis in Childhood. PMID- 21031751 TI - Enuresis in Hospital Practice. PMID- 21031753 TI - The Laevulose Test in Rheumatic and Choreic Children. PMID- 21031752 TI - A Case of Purulent Pericarditis Following Acute Osteomyelitis. PMID- 21031754 TI - Studies of Pneumonia in Childhood: II. Alveolar (Lobar) Pneumonia. PMID- 21031755 TI - The Estimation of the Phase of the Disease in Rickets. PMID- 21031756 TI - Studies of Pneumonia in Childhood: III. Broncho-Pneumonia. PMID- 21031757 TI - A Statistical Study of the Rate of Skeletal Growth in Juvenile Diabetes. PMID- 21031758 TI - Glucose Tolerance and the Blood-sugar Curve in Childhood. PMID- 21031759 TI - Infections as a source of Recurrent Epileptiform Seizures in Children. PMID- 21031760 TI - The Intelligence of Epileptic Children. PMID- 21031761 TI - The Effect of Variation of the Diet in Rheumatic Children. PMID- 21031762 TI - Topography and Pathogenesis of Lesions in Rheumatic Fever. PMID- 21031763 TI - Extensive Visceral Endarteritis Obliterans in a Young Child. PMID- 21031765 TI - Arachnodactyly. PMID- 21031764 TI - Studies of Pneumonia in childhood: IV. Bronchiectasis and Fibrosis of the Lung. PMID- 21031766 TI - Hereditary Ectodermal Dysplasia. PMID- 21031768 TI - Displacement of the Heart in Pneumonia in Childhood. PMID- 21031767 TI - A Case of Probable Antenatal Tuberculous Infection. PMID- 21031769 TI - Paroxysmal Sneezing in Whooping Cough. PMID- 21031771 TI - Congenital Valvular Obstruction of the Urethra. PMID- 21031772 TI - Acute Sensitization in an Infant to Cow's Milk Protein. PMID- 21031770 TI - The Leucocyte Count in Rheumatic Heart Disease in Childhood. PMID- 21031773 TI - Studies of Pneumonia in Childhood: V. Empyema. PMID- 21031776 TI - The Carbon Dioxide Dissociation Curve of the Blood in Infancy and Childhood. PMID- 21031774 TI - Note on the Bacteriology of Broncho-Pneumonia of Children. PMID- 21031775 TI - The Acid-Base Equilibrium of the Blood in Acute Rheumatism. PMID- 21031777 TI - The Cardiac Clinic and Hospital-Their Value in the Control of the Rheumatic Infection. PMID- 21031778 TI - Tonsillectomy in the Prevention and Treatment of Rheumatism. PMID- 21031779 TI - Non-Tuberculous Plastic Pleurisy in Children. PMID- 21031781 TI - Congenital Cardiac Disease in Identical Twins. PMID- 21031780 TI - Pulmonary Embolism in Childhood. PMID- 21031782 TI - Changes in the Blood Chemistry in Congenital Hypertrophic Pyloric Stenosis and Their Clinical Significance. PMID- 21031783 TI - Obstruction of the OEsophagus in Childhood. PMID- 21031784 TI - Remote Prognosis of Pneumonia. PMID- 21031785 TI - A Case of Coarctation of the Aorta. PMID- 21031786 TI - Hereditary Hypertelorism Without Mental Deficiency. PMID- 21031787 TI - Note on a Family with Brachydactyly. PMID- 21031788 TI - Metabolic Study of an Alkaptonuric Infant. PMID- 21031789 TI - Rheumatic Pericarditis in Childhood. PMID- 21031791 TI - Some Studies on Calcium and Phosphorus Concentration in the Small and Large Intestines of Children. PMID- 21031790 TI - Calcium and Phosphorus Meta-Bolism in some older Children on mixed diet including a Large or a Small Quantity of Milk. PMID- 21031792 TI - Salt Content of Woman's Milk in some cases in which its use was not beneficial. PMID- 21031793 TI - The Protein and Non-Protein Fractions of some samples of Woman's Milk. PMID- 21031794 TI - Treatment of Chorea by Nirvanol. PMID- 21031796 TI - Five Cases of Post-Influenzal Erythema Nodosum. PMID- 21031795 TI - The Nirvanol Treatment of Chorea. PMID- 21031797 TI - Streptococcal Allergy In Acute Rheumatic Infection. PMID- 21031798 TI - A Case of Enterogenous Methaemoglobinaemia (?Congenital) in a Child. PMID- 21031799 TI - An Unusual Case of Congenital Pyloric Stenosis. PMID- 21031800 TI - Chlorides in the Cerebro-Spinal Fluid in cases of Meningitis. PMID- 21031801 TI - Gastromegaly from Chronic Duodenal Ulcer in a Child. PMID- 21031803 TI - Two Cases of Varicella Encephalitis. PMID- 21031802 TI - Gastric Secretion in Infants and Children. PMID- 21031804 TI - A Clinical and Biochemical Study of the Subnormal Child. PMID- 21031805 TI - Gastromegaly and Chronic Duodenal Ileus in Children. PMID- 21031807 TI - The Significance of the Protein Content of the Cerebro-Spinal Fluid. PMID- 21031806 TI - Occlusion of the Hepatic Veins with Cirrhosis of the Liver. PMID- 21031808 TI - Human Contagion and Tuberculous Infection in Childhood. PMID- 21031809 TI - Metabolic Reactions to Acidosis Produced by Ammonium Chloride. PMID- 21031811 TI - A Right-sided True Diaphragmatic Hernia with Unusual Features. PMID- 21031810 TI - A Case of Exophthalmic Goitre. PMID- 21031812 TI - The Asthmatic Child. PMID- 21031813 TI - Pulmonary Lesions in Rheumatism. PMID- 21031814 TI - The Infantile Type of Gaucher's Disease. PMID- 21031815 TI - Three Sporadic Cases of Infection due to Salmonella Type Dublin. PMID- 21031817 TI - The Results of Decapsulation in Nephritis. PMID- 21031816 TI - Haemoglobinuria in the Newborn. PMID- 21031818 TI - Second Attacks of Acute Poliomyelitis, and the Minimal Duration of Immunity. PMID- 21031819 TI - Anaemia and Liver Therapy in Infancy and Childhood. PMID- 21031820 TI - Spontaneous Nystagmus in Congenital Syphilis. PMID- 21031821 TI - The Tonsils and Nasopharyngeal Epidemics. PMID- 21031822 TI - Meningeal Haemorrhage in the New-Born. PMID- 21031824 TI - Intra-Peritoneal Therapy in the Diseases of Children. PMID- 21031823 TI - A Nomogram for Use in Infant Feeding. PMID- 21031825 TI - Abdominal Symptoms in Acute Rheumatism. PMID- 21031826 TI - The Blood Constituents in Acute Rheumatism Before and After Salicylate Treatment. PMID- 21031827 TI - The Nirvanol Treatment of Chorea. PMID- 21031828 TI - The Treatment of Swift's Disease (Erythroedema). PMID- 21031829 TI - The Relationship of Throat Infection to Acute Rheumatism in Childhood. PMID- 21031830 TI - The Value of Different Therapeutic Agents in the Treatment of Rickets. PMID- 21031831 TI - The Immunology of Scarlet Fever: An Unusual Case. PMID- 21031833 TI - Spinal Tumours in Childhood. PMID- 21031834 TI - A Clinical Study of Nutritional Xerophthalmia and Night-Blindness. PMID- 21031832 TI - Prognosis in Bronchiectasis. PMID- 21031835 TI - Observations on the Chloride Metabolism in Congenital Pyloric Stenosis. PMID- 21031836 TI - Pneumonia in Measles. PMID- 21031838 TI - Otitis Media with Purulent Meningitis in an Infant Nine Days Old. PMID- 21031837 TI - Observations on the Milk of New Zealand Women. PMID- 21031839 TI - Two Cases of Sub-Acute Hepatic Necrosis. PMID- 21031840 TI - A Case of Congenital Hypertrophic Pyloric Stenosis. PMID- 21031841 TI - Post-Anginal Sepsis: (Sepsis of Oro-Naso-Pharyngeal Origin). PMID- 21031842 TI - The Surgical Anatomy of Rammstedt's Operation. PMID- 21031843 TI - Metabolism Studies in Coeliac Disease. PMID- 21031844 TI - A Method of Study of Intracranial Haemorrhage in the New-Born Infant. PMID- 21031845 TI - Pink Disease: its Morbid Anatomy, with a Note on Treatment. PMID- 21031847 TI - Acute and Chronic Non-Tuberculous Pyuria in Children. PMID- 21031846 TI - Malignant Hypertension in Childhood. PMID- 21031848 TI - Distribution of the Phosphorus Compounds and Calcium in the Blood of Children. PMID- 21031850 TI - Two Cases of Double Ureter. PMID- 21031849 TI - Calcium and Phosphorus Metabolism in Nephritis. PMID- 21031851 TI - The Incidence of Undulant Fever in Children. PMID- 21031853 TI - A Case of Perforated Duodenal Ulcer in an Infant. PMID- 21031852 TI - Familial Splenic Anaemia. PMID- 21031854 TI - Enuresis of Allergic Origin. PMID- 21031855 TI - The Electrocardiogram of Normal School Children. PMID- 21031856 TI - Congenital Anomalies of the Heart in Elementary School Children. PMID- 21031857 TI - The Value of Alkali in Salicylate Therapy. PMID- 21031858 TI - Some Effects of a Ketogenic Diet. PMID- 21031859 TI - Alkalosis in the Vomiting of Infancy. PMID- 21031860 TI - Race, Rheumatism and Growing Pains. PMID- 21031862 TI - The Clinical Interpretation of Some Haemorrhagic States. PMID- 21031861 TI - Three Cases of Duodenal Obstruction in the New-Born. PMID- 21031863 TI - A Case of Severe Anaemia in a New-born Infant. PMID- 21031865 TI - Gangrene in an Infant Associated with Temporary Diabetes. PMID- 21031864 TI - A Study of the Blood Cholesterol in Childhood. PMID- 21031866 TI - The Multiple Puncture Cutaneous Tuberculin Test. PMID- 21031867 TI - Studies in Juvenile Rheumatism. PMID- 21031868 TI - Benign Tuberculous Infiltration of the Lung (Epituberculosis). PMID- 21031869 TI - Congenital Obstruction of the Female Urethra. PMID- 21031870 TI - Lymphocytic Leukaemia Causing Pontine Haemorrhage. PMID- 21031871 TI - Tumour of the Suprarenal Cortex in an Infant of 18 weeks. PMID- 21031872 TI - Umbilical Diphtheria. PMID- 21031873 TI - Effect of Ammonium Chloride Administration on Metabolism in Infantile Tetany and Rickets. PMID- 21031874 TI - Rickets in Sydney, Australia. PMID- 21031875 TI - Kala-Azar in Children of North China. PMID- 21031877 TI - Multiple Cases of Erythema Nodosum in a Class of School Children. PMID- 21031876 TI - Further Note on Gastromegaly from Duodenal Ileus. PMID- 21031878 TI - The Extent of the Pancreatic Lesions in Diabetic Children. PMID- 21031879 TI - Difficult and Defective Children. PMID- 21031880 TI - Four Cases of Urinary Obstruction. PMID- 21031881 TI - Investigations on the Causes of Vaccination Encephalitis. PMID- 21031882 TI - Amyoplasia Congenita: (Multiple congenital articular rigidity: Arthrogryposis multiplex congenita). PMID- 21031883 TI - Osteopsathyrosis (Lobstein's disease): A Critical Review. PMID- 21031885 TI - Acute Otitis Media in Infancy. PMID- 21031884 TI - The Plasma Phosphatase in Rickets and Scurvy. PMID- 21031886 TI - The Influence of Acidosis on Carbohydrate Metabolism. PMID- 21031888 TI - Chronic Intussusception in Children. PMID- 21031887 TI - Lesions of the Pharynx in Acute Rheumatism. PMID- 21031889 TI - A Case of Dwarfism and Calcinosis: Associated with Widespread Arterial Degeneration. PMID- 21031890 TI - A Case of Sub-acute Intussusception with Skiagrams. PMID- 21031891 TI - The Treatment of Kala Azar in Children. PMID- 21031892 TI - Rickets, Congenital Syphilis and Achondroplasia in the Same Child. PMID- 21031893 TI - A Case of Haemorrhagic Nephritis in a Newborn Baby. PMID- 21031894 TI - Experimental Study of the Antirachitic Factor in Human and Animal Milks. PMID- 21031895 TI - The Position of the Large Intestine in Infants and its Relation to Constipation. PMID- 21031896 TI - The Specificity of Haemoglobins including Embryonic Haemoglobin. PMID- 21031897 TI - Vincent's Infection in Childhood. PMID- 21031899 TI - Sinusitis in Childhood. PMID- 21031898 TI - The Use of Radiostoleum and Calcium Salts in Rheumatism. PMID- 21031900 TI - Tuberculous Laryngitis in Children. PMID- 21031901 TI - Patent Ductus Arteriosus. PMID- 21031902 TI - Obesity after Chorea. PMID- 21031903 TI - Otitis Media as an AEtiological Factor in Gastro-Enteritis. PMID- 21031904 TI - Osseous Dystrophy following Icterus Gravis Neonatorum. PMID- 21031905 TI - Rickets following an attack of Acute Nephritis. PMID- 21031906 TI - Observations on Dysentery in Children. PMID- 21031907 TI - Ovarian Sarcoma in Children. PMID- 21031908 TI - On the AEtiology and Treatment of Pink Disease. PMID- 21031909 TI - The Non-Protein Nitrogen of the Blood in Health and in Hepatic Disease. PMID- 21031910 TI - Atelectatic Bronchiectasis in Childhood. PMID- 21031911 TI - Ketogenic Diet in the Treatment of Pyuria in Childhood. PMID- 21031912 TI - A Case of Papilloma of the Choroid Plexus. PMID- 21031913 TI - The Haemolytic Streptococcus as a Factor in the Causation of Acute Rheumatism. PMID- 21031915 TI - A Review of the Use of Immune Serum in Acute Poliomyelitis. PMID- 21031914 TI - Renal Rickets Following Acquired Nephritis. PMID- 21031916 TI - Studies in the Anaemias of Infancy and Early Childhood: Part III. The anhaematopoietic anaemias (deficiency diseases of the erythron): nutritional anaemia, and the anaemias of prematurity, scurvy and coeliac disease. PMID- 21031918 TI - A Case of Megaduodenum with Multiple Anomalies of the Ileum. PMID- 21031917 TI - Copper in the Treatment of Nutritional Anaemia in Infancy. PMID- 21031919 TI - Studies in the Anaemias of Infancy and Early Childhood: Part I. Introduction. PMID- 21031920 TI - Studies in the Anaemias of Infancy and Early Childhood: Part II. The effect of yeast on nutritional anaemia in rats. PMID- 21031921 TI - Studies in the Anaemias of Infancy and Early Childhood: Part IV. The haemolytic (erythronoclastic) anaemias of the neonatal period; with special reference to erythroblastosis of the new born. PMID- 21031923 TI - Gastromegaly in children. PMID- 21031922 TI - Studies in the Anaemias of Infancy and Early Childhood: Part V. The haemolytic (erythronoclastic) anaemias of later infancy and childhood: with special reference to the acute haemolytic anaemia of Lederer and the anaemia of von Jaksch. PMID- 21031924 TI - Plasma phosphatase in rickets and other disorders of growth. PMID- 21031926 TI - Studies in the Anaemias of Infancy and Early Childhood: Part VI. Nutritional anaemia in mother and child. PMID- 21031925 TI - The normal haemoglobin level during the first year of life: revised figures. PMID- 21031927 TI - Studies in the Anaemias of Infancy and Early Childhood: Part VII. Monocytic reaction in myelosis. PMID- 21031929 TI - Renal Rickets associated with parathyroid hyperplasia. PMID- 21031928 TI - Factors causing variation in the haemoglobin level with age in the first year of life. PMID- 21031930 TI - On the occurrence of sex-linked variations in twins. PMID- 21031931 TI - Studies in the Anaemias of Infancy and Early Childhood: Part VIII. Leukaemia (leucosis) in Children. PMID- 21031932 TI - On the incidence of congenital hypertrophic pyloric stenosis in the 17th and 18th centuries. PMID- 21031933 TI - Circumscribed cerebral tumours in young infants. PMID- 21031934 TI - A case of amyoplasia congenita, with pathological report. PMID- 21031935 TI - The metabolism of healing in coeliac rickets. PMID- 21031936 TI - Studies in the Anaemias of Infancy and Early Childhood: Part IX. Anaemia and reticulo-endotheliosis. PMID- 21031937 TI - Lipiodol in the diagnosis of congenital oesophageal atresia. PMID- 21031938 TI - Double aortic arch. PMID- 21031940 TI - Infantile sepsis and its nutritional effects. PMID- 21031939 TI - The incidence of sugars in the urine of infants and children. PMID- 21031942 TI - A case of late infantile amaurotic idiocy: With pathological report. PMID- 21031941 TI - A nutritional disease of childhood associated with a maize diet. PMID- 21031943 TI - Patent interventricular septum (maladie de Roger). PMID- 21031944 TI - Familial sex-linked ectodermal dysplasia with incomplete forms. PMID- 21031945 TI - Arterial pressure in normal Serbian children. PMID- 21031946 TI - Chondrodysplasia in twins. PMID- 21031948 TI - Investigations on glycogen disease. PMID- 21031947 TI - Duodenal ulcers in the new born. PMID- 21031949 TI - Pyelonephritis in infancy and childhood: its bacteriology and pathology. PMID- 21031950 TI - A nutritional disease of childhood associated with a maize diet-and pellagra. PMID- 21031951 TI - Pyelography in infants. PMID- 21031952 TI - Unusual case of disseminated sarcoma in a child. PMID- 21031953 TI - Vitamin A deficiency in children: Part I. Present knowledge of the clinical effects of vitamin A deficiency, with special reference to children. PMID- 21031955 TI - Vitamin A Deficiency in Children: Part II.-Vitamin A requirements of babies: Skin lesions and vitamin A deficiency. PMID- 21031954 TI - The solar irradiation of children with special reference to hypervitaminosis D. PMID- 21031956 TI - An Epidemic of Acute Encephalitis in Young Children. PMID- 21031957 TI - The Aetiology of Idioglossia. PMID- 21031958 TI - The Intradermal Tuberculin Reaction: With special reference to so-called surgical tuberculosis. PMID- 21031959 TI - Sensitivity to Cow's Milk Proteins in Acute Gastro-Enteritis. PMID- 21031960 TI - Five cases of congenital lung cyst. PMID- 21031961 TI - The Klippel-Feil syndrome: (Congenital webbed neck). PMID- 21031962 TI - Congenital absence of the abdominal muscles. PMID- 21031964 TI - The after history of cases of pleurisy with serous effusion in children. PMID- 21031963 TI - Glissonian rickets. PMID- 21031965 TI - Bone and vegetable broth. PMID- 21031966 TI - Acid metabolism in rheumatic children. PMID- 21031967 TI - Coronary endarteritis in acute rheumatism. PMID- 21031968 TI - Gout and aleukaemic leukaemia in a boy aged five. PMID- 21031969 TI - The sedimentation rate in rheumatic carditis. PMID- 21031970 TI - Nephritis in infancy. PMID- 21031971 TI - Inherited smallpox. PMID- 21031972 TI - Bone changes in leukaemia: Part I.-Clinical and roentgenological. PMID- 21031973 TI - The gastric secretion in normal and rheumatic children. PMID- 21031975 TI - Cutaneous myiasis in infants. PMID- 21031974 TI - The urea clearance test in children. PMID- 21031976 TI - The haematology of infantile sepsis. PMID- 21031977 TI - Pollen sensitiveness in children with asthma. PMID- 21031978 TI - Iron-deficiency anaemia in children: Its association with gastro-intestinal disease, achlorhydria and haemorrhage. PMID- 21031979 TI - The relapse in scarlet fever. PMID- 21031981 TI - The incidence of the various types of pneumococci in infections other than pneumonia. PMID- 21031980 TI - Actinomycosis in childhood: A clinical study and review. PMID- 21031982 TI - Papular urticaria (lichen urticatus). PMID- 21031983 TI - Obsessive-compulsive states in childhood and their treatment. PMID- 21031984 TI - Blood transfusion in the malnutrition of infancy. PMID- 21031985 TI - The red corpuscles in acidosis and alkalosis. PMID- 21031986 TI - Atelectatic or compensatory bronchiectasis. PMID- 21031987 TI - Osteomyelitis of the maxilla in the newly-born. PMID- 21031988 TI - Gastric secretion in coeliac disease. PMID- 21031989 TI - Carcinoma of the thyroid gland in childhood: With Report of a Case. PMID- 21031990 TI - Infective reticulo-endotheliosis chiefly localized in lungs, bone marrow and thymus. PMID- 21031991 TI - The gastric secretion in anaemia. PMID- 21031992 TI - A case of coeliac disease showing unusual features successfully treated with insulin and glucose. PMID- 21031993 TI - Remarks on heredity in relation to tuberculosis. PMID- 21031994 TI - A statistical study of nocturnal enuresis. PMID- 21031996 TI - The early anaemia of Premature infants: The haemoglobin level of immature babies in the first half-year of life and the effect during the first three months of blood injections and iron therapy. PMID- 21031995 TI - Gastromegaly from arterio-mesenteric compression of the duodenum in the new-born. PMID- 21031997 TI - Infantile scurvy: its history. PMID- 21031999 TI - On cases described as 'acute rickets'. PMID- 21031998 TI - Dr. Cheadle and infantile scurvy. PMID- 21032001 TI - The recognition of scurvy with especial reference to the early x-ray changes. PMID- 21032000 TI - The isolation and identification of vitamin C. PMID- 21032002 TI - Vitamin C and its effects on the structure of the teeth. PMID- 21032003 TI - Malnutrition and latent scurvy. PMID- 21032004 TI - The Vitamin C content of the liver of newborn infants. PMID- 21032005 TI - Investigations into the pathogenesis of scorbutic dystrophy. PMID- 21032006 TI - Studies in the anaemia of infancy and early childhood: Part X.-The anaemia of infantile scurvy. PMID- 21032007 TI - Urinary disorders occurring in the neonatal period. PMID- 21032009 TI - Recurrent swelling of the parotid glands. PMID- 21032008 TI - Blood counts of newborn infants in relation to icterus neonatorum. PMID- 21032010 TI - A further study of the antirachitic factor in human milk. PMID- 21032011 TI - An enquiry into the value of autohaemotherapy in juvenile asthma. PMID- 21032012 TI - Ketogenic diet in persistent pyuria. PMID- 21032013 TI - Coma with glycosuria not due to diabetes mellitus. PMID- 21032014 TI - A study of the sedimentation rate in juvenile rheumatism. PMID- 21032016 TI - Four cases of familial acholuric jaundice: The effect of splenectomy on red cell morphology. PMID- 21032015 TI - A note on the serum proteins in normal infants and children. PMID- 21032017 TI - Skin reactions to products of the haemolytic streptococcus. PMID- 21032018 TI - The medical treatment of congenital pyloric stenosis. PMID- 21032019 TI - Dwarfism with retinal atrophy and deafness. PMID- 21032020 TI - Blood volume and circulation time in children. PMID- 21032021 TI - The role of muscle in obesity. PMID- 21032022 TI - A contribution to the pathology of identical twins. PMID- 21032023 TI - The value of oestrin for premature babies. PMID- 21032024 TI - Further observations on pink disease. PMID- 21032025 TI - The oxydase reaction of human milk. PMID- 21032026 TI - Epituberculosis. PMID- 21032027 TI - Encephalography in the investigation of certain cerebral conditions in childhood: Part I. PMID- 21032028 TI - Diagnosis of pulmonary middle lobe disease in children. PMID- 21032030 TI - Reading difficulties in children. PMID- 21032029 TI - The therapeutic value of vitamins A and D in measles. PMID- 21032032 TI - Encephalography in the investigation of certain cerebral conditions in childhood: Part II. PMID- 21032031 TI - The use of avertin for the production of basal narcosis in children. PMID- 21032033 TI - Meningitis in the newborn. PMID- 21032034 TI - Parental loss and child guidance. PMID- 21032035 TI - Staphylococcal pneumonia. PMID- 21032036 TI - Ectopia cordis cum sterni fissura. PMID- 21032038 TI - Morquio's disease: Report of two cases. PMID- 21032037 TI - The carbohydrate metabolism in abdominal tuberculosis. PMID- 21032039 TI - Subcutaneous rheumatic nodules with no carditis. PMID- 21032041 TI - The ossification of the carpus in rickets, congenital syphilis and cretinism. PMID- 21032040 TI - Banti's syndrome in childhood: A report of four cases. PMID- 21032042 TI - The blood-sugar in convulsions of infancy and childhood. PMID- 21032044 TI - Amyoplasia congenita associated with mongolism. PMID- 21032043 TI - Further observations on acid metabolism in rheumatic children. PMID- 21032046 TI - Congenital tricuspid atresia. PMID- 21032045 TI - Congenital obliteration of the bile ducts. PMID- 21032047 TI - Accessory nasal sinusitis in childhood: With a record of bacteriological examinations. PMID- 21032048 TI - Creatine metabolism and the gonads. PMID- 21032050 TI - Solitary cyst of the liver in a child aged four months. PMID- 21032049 TI - Infantilism with bony changes resembling rickets and calcification in kidneys. PMID- 21032051 TI - Massive atelectatic bronchiectasis associated with bronchial stenosis. PMID- 21032052 TI - Chronic miliary tuberculosis in children. PMID- 21032053 TI - Milk curd-its mechanism and modification. PMID- 21032054 TI - The significance of plasma phosphatase in the diagnosis and prognosis of rickets. PMID- 21032055 TI - Persistent truncus arteriosus communis with microphthalmos, orbital cyst and polydactyly. PMID- 21032056 TI - Abnormal expansion of the lungs in an infant. PMID- 21032057 TI - Delinquency in relation to the broken home. PMID- 21032059 TI - Congenital absence of the pectoral muscles. PMID- 21032058 TI - Spontaneous pneumothorax of the newly-born. PMID- 21032060 TI - A case of the Klippel-Feil syndrome. PMID- 21032061 TI - Familial progressive diffuse cerebral sclerosis of infants. PMID- 21032062 TI - Plasma phosphatase and phosphorus during the healing of fractures in children. PMID- 21032063 TI - The iron-deficiency anaemia of late infancy. PMID- 21032064 TI - Cerebral sinus thrombosis in children. PMID- 21032065 TI - Congenital obliteration of the bile ducts: In a child who lived for three years and three months. PMID- 21032066 TI - An investigation into the health of 1,530 pre-school children. PMID- 21032067 TI - The effect of boiling on the nutritive value of milk. PMID- 21032068 TI - Nuclear jaundice in neonatal (umbilical) sepsis with jaundice. PMID- 21032069 TI - Three cases of non-bacterial meningitis. PMID- 21032070 TI - Primary tuberculosis of the skin. PMID- 21032071 TI - Pellagra in African children. PMID- 21032072 TI - Vitamin B(1) deficiency in infancy: A Critical Review. PMID- 21032073 TI - Variations in the first heart sound and the auriculo-ventricular conduction time in children with rheumatic fever. PMID- 21032074 TI - Dysentery in infancy. PMID- 21032075 TI - Erythema marginatum (rheumaticum). PMID- 21032076 TI - Acute myeloid leukaemia in one of identical twins. PMID- 21032077 TI - The prognosis in rheumatoid arthritis in childhood. PMID- 21032078 TI - Tumours of the sympathetic nervous system in children: A study of twenty-five cases. PMID- 21032079 TI - Cerebral tumours in children: A pathological report. PMID- 21032081 TI - The demonstration of the tubercle bacillus in the pulmonary tuberculosis of childhood. PMID- 21032080 TI - Studies on the retention of iron in childhood. PMID- 21032082 TI - Generalized cutaneous vaccinia. PMID- 21032083 TI - I.-Clinical aspects of Infantile diarrhoea. PMID- 21032084 TI - II.-Chemical changes in the blood in infantile diarrhoea and the effect of intravenous administration of fluid. PMID- 21032085 TI - III.-Changes in water and chloride content of the tissues in infantile diarrhoea and other conditions. PMID- 21032086 TI - Part XI.-The effect of iron deficient diets on the size of the red blood cells in rats and in the production of microcytic hypochromic anaemia in their offspring; a contribution to the study of congenital iron-deficiency anaemia in the human infant. PMID- 21032087 TI - Continuous intravenous drip in infants and children. PMID- 21032088 TI - Atrophic cirrhosis of the liver following icterus gravis neonatorum. PMID- 21032089 TI - Hypertrophic pyloric stenosis without symptoms. PMID- 21032090 TI - Papilloma of the choroid plexus in an infant. PMID- 21032091 TI - The treatment of renal rickets. PMID- 21032092 TI - A case of periarteritis nodosa with subcutaneous lesions and recovery. PMID- 21032093 TI - Congenital steatorrhoea due to pancreatic defect. PMID- 21032094 TI - The administration of thyroid gland to premature babies. PMID- 21032096 TI - A standard intravenous glucose tolerance test. PMID- 21032095 TI - Undulant fever in children. PMID- 21032097 TI - Paraplegia and mongolism in twins. PMID- 21032098 TI - A foreign body in the kidney. PMID- 21032099 TI - Vitamin C excretion in children, with particular reference to rheumatic fever. PMID- 21032101 TI - Radiology in the diagnosis of hypertrophic pyloric stenosis. PMID- 21032100 TI - Otitis Media and mastoiditis in infancy. PMID- 21032102 TI - The blood phosphorus in Egyptian infants. PMID- 21032103 TI - Osteopetrosis. PMID- 21032104 TI - The Cooley syndrome in an English child. PMID- 21032105 TI - A case of diabetes mellitus in a young infant. PMID- 21032106 TI - Intracranial Haemorrhage in the new-born: A study of diagnosis and differential diagnosis based upon pathological and clinical findings in 126 cases. PMID- 21032107 TI - Wilms' embryoma: A Clinico-Pathological Study. PMID- 21032109 TI - Symmetrical degeneration of the neostriatum in Chinese infants. PMID- 21032108 TI - Oesophagitis in infancy. PMID- 21032110 TI - Clinical ascariasis in children. PMID- 21032111 TI - Precocious puberty with a report on a case of pineal syndrome. PMID- 21032112 TI - Congenital pyloric stenosis in first and second consins. PMID- 21032113 TI - Nutritional oedema in children in Egypt. PMID- 21032114 TI - Spontaneous subarachnoid haemorrhage in children. PMID- 21032115 TI - Congenital haemolytic anaemia with normal fragility of the red blood cells. PMID- 21032116 TI - Hydatid cyst of the spinal canal successfully treated by operation. PMID- 21032117 TI - Tetany in the new-born. PMID- 21032119 TI - The determination of glucose tolerance. PMID- 21032118 TI - Cranio-carpo-tarsal dystrophy. PMID- 21032121 TI - The causative organisms of bronchopneumonia in infants in Egypt. PMID- 21032122 TI - Chinese methods of infant feeding and nursing. PMID- 21032120 TI - Peripheral brachial paralysis in infants and Children. PMID- 21032124 TI - Gangrene of the extremities in an infant. PMID- 21032123 TI - Nutritional anaemia in an industrial district. PMID- 21032125 TI - Congenital mitral stenosis. PMID- 21032126 TI - Observations on the descent of the testicle with special reference to spontaneous descent at puberty. PMID- 21032127 TI - Cardiomegalia glycogenica circumscripta. PMID- 21032128 TI - Transient lung consolidation in asthmatic children with reference to eosinophilia. PMID- 21032129 TI - The relationship between acute rheumatism and streptococcal antifibrinolysin. PMID- 21032130 TI - A statistical note on gastro-intestinal disorders in infants. PMID- 21032131 TI - The apple treatment of infantile diarrhoea. PMID- 21032132 TI - Vitamin-resistant rickets. PMID- 21032133 TI - A case of arachnodactyly. PMID- 21032134 TI - A case of morquio's disease. PMID- 21032135 TI - Besnier-boeck's disease in an infant. PMID- 21032136 TI - A medulloblastoma in an infant with abnormal cells in the cerebrospinal fluid. PMID- 21032137 TI - Temporary hemiplegia following symptomatic convulsions. PMID- 21032138 TI - The association of gall-stones with acholuric jaundice in children: Report of A Case in a Child Aged Three Years with a Note on the Crises of Acholuric Jaundice. PMID- 21032139 TI - The after-history of premature infants: With Special Reference to the Effect of the Birth Weight on the Weight Chart. PMID- 21032140 TI - The ultimate prognosis of nephritis in childhood: Together with a Study of the Incidence of Anaemia in the Various Stages of the Disease. PMID- 21032141 TI - Absorption studies in children with giardia lamblia infection: A Preliminary Report. PMID- 21032142 TI - The blood and spinal fluid sugar and chloride content in meningitis. PMID- 21032143 TI - Eumydrine in pyloric stenosis. PMID- 21032144 TI - Biliary cirrhosis. PMID- 21032146 TI - Epiphyseal necrosis in pituitary gigantism. PMID- 21032145 TI - Osseous dystrophy following icterus gravis neonatorum: Generalized Osteitis Fibrosa with Areas of Pigmentation of the Skin and Precocious Puberty in the Female. PMID- 21032147 TI - Dysostosis multiplex: Pfaundler-Hurler syndrome. PMID- 21032148 TI - Monocytic leukaemia in childhood. PMID- 21032149 TI - Vitamin A requirements of infants: The Health of Infants Fed on Roller-Process Dried Milk, with and without a Supplement of Vitamin A. PMID- 21032150 TI - A review of twenty years of breast feeding in Liverpool. PMID- 21032152 TI - Renal lesions in children with erythema nodosum. PMID- 21032151 TI - Inguinal hernia in female twins: With Special Reference to the Identification of Monozygotism. PMID- 21032153 TI - Prognosis in coeliac disease: A Review of Seventy-Three Cases. PMID- 21032154 TI - The use of irradiated evaporated milk in infant feeding. PMID- 21032156 TI - Iron-resistant anaemia and latent rickets in schoolchildren. PMID- 21032157 TI - Pneumonia in the new-born. PMID- 21032155 TI - The cause of reduction of the sugar content of the cerebrospinal fluid in meningitis. PMID- 21032158 TI - Cerebral oedema in scarlet fever. PMID- 21032159 TI - Trichobezoar (hairball) causing acute intestinal obstruction in a child aged three years. PMID- 21032160 TI - Soya Bean Flour with Dried Milk: A Cheap and Efficient Substitute for Breast Milk. PMID- 21032162 TI - Stomatitis in Childhood. PMID- 21032161 TI - The Schilling Haemogram in Otitis Media and Mastoiditis of Infancy. PMID- 21032163 TI - Staphylococcus Aureus Infection of the Long Bones in the Newly Born. PMID- 21032165 TI - Lingual Application of Eumydrin in the Treatment of Congenital Pyloric Stenosis. PMID- 21032164 TI - Hepatosplenomegaly Resembling Niemann-Pick's Disease: Recovery Following Liver Therapy. PMID- 21032167 TI - Fenestrae Parietales Symmetricae. PMID- 21032166 TI - Extroversion of the Primitive Hind Gut. PMID- 21032168 TI - The Importance of Bronchoscopy in the Recognition of Non-Opaque Foreign Body in Infants and Children. PMID- 21032170 TI - The Clinical Picture of Staphylococcal Infections in the Newborn. PMID- 21032169 TI - A Syndrome Characterized by Ectodermal Dysplasia, Polydactyly, Chondro-Dysplasia and Congenital Morbus Cordis: Report of Three Cases. PMID- 21032171 TI - Vitamin K in Prenatal Prevention and Postnatal Treatment of Haemorrhagic Disease of the Newborn. PMID- 21032172 TI - Generalized Angiomatosis Presenting the Clinical Characteristics of Storage Reticulosis: With Some Observations on the Reticulo-Endothelioses. PMID- 21032174 TI - A Simple Specific Precipitation Test for Cow's Milk. PMID- 21032173 TI - Sternal Marrow Puncture in Children. PMID- 21032175 TI - Rheumatic Heart Disease in Identical Twins. PMID- 21032176 TI - The Incidence of the Four Main Blood Groups in Rheumatic Heart Disease. PMID- 21032177 TI - Carbohydrate Tolerance in Hypothyroidism and Hyperthyroidism. PMID- 21032178 TI - Broncho-Pneumonia in a Cretin before and after Treatment with Thyroid. PMID- 21032179 TI - Gargoylism: A Review of the Principal Features with a Report of Five Cases. PMID- 21032180 TI - Gargoylism: Report of an Additional Case of Gargoylism. PMID- 21032181 TI - Proliferative Mural Bronchiolitis. PMID- 21032182 TI - Gaucher's Disease: Diagnosis by Sternal Puncture and Improvement Following Splenectomy. PMID- 21032183 TI - Nerve-Cell Swelling of the Juvenile Amaurotic Family Idiocy Type: Associated with Tuberose Sclerosis in an Infant Aged Twelve Months. PMID- 21032184 TI - The Blood Cholesterol Content in Childhood. PMID- 21032186 TI - Congenital Cyst of the Larynx Causing Fatal Asphyxia Neonatorum. PMID- 21032185 TI - Arachnodactyly and Ectopia Lentis in a Father and Daughter. PMID- 21032187 TI - Volvulus in a Three-Weeks-Old Baby with a Meckel's Diverticulum and Congenital Morbus Cordis. PMID- 21032188 TI - Eumydrin in the treatment of hypertrophic pyloric stenosis: An analysis of 40 consecutive cases. PMID- 21032189 TI - Observations on the gastric acidity during the first month of life. PMID- 21032190 TI - A comparison of breast-feeding in ten classes of the population. PMID- 21032191 TI - Gargoylism: Report of four cases. PMID- 21032192 TI - Infantilism, obesity and retinal dystrophy: A 'Forme Fruste' of the Laurence-Moon Biedl syndrome. PMID- 21032193 TI - Desoxycorticosterone acetate and oestradiol dipropionate therapy in the newborn infant. PMID- 21032195 TI - Malignant hypertension in childhood. PMID- 21032194 TI - A survey of primary infantile and juvenile pneumonia. PMID- 21032196 TI - Combined forms of meningitis: Mixed infection of the meninges by the tubercle bacillus and meningococcus. PMID- 21032197 TI - The changes in the blood produced by dehydration in infancy. PMID- 21032198 TI - The diagnosis and conservative treatment of bronchiectasis in children. PMID- 21032199 TI - Address at a memorial service. PMID- 21032200 TI - George Frederic Still. PMID- 21032201 TI - A handlist of the writings of George Frederic Still. PMID- 21032202 TI - On a form of chronic joint disease in children. PMID- 21032203 TI - Calorie requirements of full-term and premature infants in the neonatal period: A Formula, its Uses and Limitations. PMID- 21032204 TI - A comparison of the value of crystalloid solutions, whole blood and blood plasma in the treatment of dehydration in infancy. PMID- 21032205 TI - A case showing combined features of acute rheumatism and rheumatoid arthritis. PMID- 21032206 TI - Infantile diarrhoea and vomiting. PMID- 21032207 TI - Shock in the newborn infant. PMID- 21032209 TI - Familial renal dwarfism. PMID- 21032208 TI - The secretion of urine by premature infants. PMID- 21032210 TI - Arachnodactyly in a Chinese infant. PMID- 21032211 TI - Extensive congenital malformation of the skin. PMID- 21032212 TI - Suppurative periarthritis in an infant due to the suipestifer bacillus. PMID- 21032213 TI - Anaemia in nephritis. PMID- 21032215 TI - Infantile muscular atrophy of spinal origin: A Report of Two Cases. PMID- 21032214 TI - A further investigation of breast-feeding: A Study of One Thousand Mothers. PMID- 21032216 TI - Growth of the lung in healthy and sick infants. PMID- 21032217 TI - A fourth type of erythroblastosis foetalis showing hepatic cirrhosis in the macerated foetus: A Report of Three Cases. PMID- 21032218 TI - Hydrocolpos in an infant. PMID- 21032219 TI - Four cases of duodenal ulceration in children simulating acute appendicitis. PMID- 21032220 TI - The secretion of urine by dehydrated and normal infants. PMID- 21032221 TI - Peptic ulcer in infancy and childhood with a review of the literature. PMID- 21032222 TI - Two cases of duodenal ulceration in children. PMID- 21032223 TI - A clinical and bacteriological survey of pneumonia in childhood. PMID- 21032224 TI - Dementia infantilis with cortical dysrhythmia. PMID- 21032225 TI - Hospital diarrhoea. PMID- 21032226 TI - Micro-method for the estimation of the sedimentation rate of red cells. PMID- 21032227 TI - Some social aspects of infant feeding. PMID- 21032228 TI - Oligodendroglioma in an infant of eight months. PMID- 21032230 TI - A case of exfoliative dermatitis of the newborn (Ritter's disease). PMID- 21032229 TI - Two cases illustrating the treatment of neonatal pneumonia. PMID- 21032231 TI - Post-vaccinial encephalitis: Recovery Following Treatment with Intravenous Pentothal Sodium and Convalescent Serum. PMID- 21032233 TI - Vitamin K requirements of the newborn. PMID- 21032232 TI - Haemorrhagic disease of the newborn. PMID- 21032234 TI - Gastric acidity during the first year of life. PMID- 21032236 TI - The relation of maternal diet to breast feeding. PMID- 21032235 TI - Bacillary dysentery. PMID- 21032237 TI - The incidence and mortality of breast- and artificially-fed infants admitted to hospital with infections. PMID- 21032239 TI - A study of the quantitative fragility test in children. PMID- 21032238 TI - Cystic fibrosis of the pancreas. PMID- 21032240 TI - Two cases of glycogen disease. PMID- 21032241 TI - Studies in the anaemias of infancy and early childhood: Part XII.-The regeneration rate of haemoglobin and the life span of erythrocytes in normal and pathological conditions. PMID- 21032243 TI - Absorption of drugs from the rectum. PMID- 21032242 TI - The nutrient enema. PMID- 21032244 TI - Intrathoracic cysts of intestinal and bronchial structure. PMID- 21032245 TI - A case of juvenile xanthomatosis: With Enlarged Liver and Spleen and Greatly Increased Plasma Lipoids. PMID- 21032247 TI - Osteomyelitis of the spine following lumbar puncture. PMID- 21032246 TI - Additional manifestation of sulphathiazole toxicity: Non-Calculous Renal Insufficiency Following the use of sulphathiazole. PMID- 21032248 TI - Primary carcinoma of the pancreas in an infant aged seven months. PMID- 21032249 TI - Coarctation of the aorta with cerebral aneurysm. PMID- 21032250 TI - Carotinaemia in a suckling. PMID- 21032251 TI - Studies in the anaemias of infancy and early childhood: Part XIII.-Experiments on blood regeneration and their significance for the life span of erythrocytes. PMID- 21032252 TI - Rheumatic infection in childhood. PMID- 21032253 TI - Plasma protein values in infants. PMID- 21032254 TI - An unusual osseous dystrophy. PMID- 21032255 TI - The first George Frederic Still Memorial Lecture: Some recent virus work and its practical import. PMID- 21032256 TI - Studies in the anaemias of infancy and early childhood: Part XIV.-The fate of transfused erythrocytes. PMID- 21032258 TI - Fibrinogen deficiency as a factor in haemorrhagic disease. PMID- 21032257 TI - Head injuries in children: And their after-effects. PMID- 21032260 TI - Arrangements for newly born babies in maternity hospitals. PMID- 21032259 TI - Report on the early diagnosis of tuberculosis in childhood. PMID- 21032261 TI - The survival of transfused erythrocytes in haemolytic disease of the newborn. PMID- 21032262 TI - Spina bifida and its associated skull defects. PMID- 21032264 TI - Intestinal thrush: A Report of Two Cases in Young Infants. PMID- 21032263 TI - Children in a tuberculosis colony: A Survey of the Papworth Children. PMID- 21032265 TI - Transection of the spinal cord due to injury at birth. PMID- 21032267 TI - The healing of renal rickets. PMID- 21032266 TI - Congenital complete heart block. PMID- 21032268 TI - Spontaneous pneumothorax, massive collapse, and subcutaneous emphysema complicating asthma. PMID- 21032269 TI - Macrocytic anaemia in children: With a Report of Three Cases Showing Megaloblastic Erythropoiesis. PMID- 21032270 TI - Refractory anaemia (Fanconi type): Its Incidence in Three Members of One Family, with in One Case a Relationship to Chronic Haemolytic Anaemia with Nocturnal Haemo-Globinuria (Marchiafava-Micheli Disease or 'Nocturnal Haemoglobinuria'). PMID- 21032271 TI - Erythroblastic anaemia with bone changes in Egyptian children: Possible Cooley's Type. PMID- 21032272 TI - Observations on the urine of the new-born infant. PMID- 21032274 TI - Glycogen storage disease. PMID- 21032273 TI - Myocarditis in acute infective diseases: A Review of 200 Cases. PMID- 21032275 TI - The incidence of rickets in war-time. PMID- 21032276 TI - The incidence of rickets in children attending hospitals in Bristol from September 1938 to May 1941. PMID- 21032277 TI - Observations on tuberculous meningitis. PMID- 21032279 TI - The care of rheumatic children: Report by the Cardiac Society and British Paediatric Association. PMID- 21032278 TI - An analysis of the fate of premature babies in Warwickshire for 1942 and 1943. PMID- 21032280 TI - Atrophic sclerosis of the cerebral cortex associated with birth injury. PMID- 21032281 TI - Prognosis and treatment of pneumonia in children. PMID- 21032282 TI - Observations on otitis media and mastoiditis in infancy. PMID- 21032283 TI - Congenital atresia of the oesophagus: An Attempt at Surgical Treatment. PMID- 21032284 TI - Giant congenital diverticula and neonatal rupture of colon: A case associated with true congenital partial hypertrophy of the crossed type. PMID- 21032285 TI - Imperforate anus: Some Observations Regarding Diagnosis of the Level of Obstruction. PMID- 21032286 TI - Allergic vomiting in an infant. PMID- 21032287 TI - Two cases of pulmonary actinomycosis. PMID- 21032288 TI - The treatment of coeliac disease with vitamin B complex and concentrated liver. PMID- 21032289 TI - A century of changes in the mortality and incidence of the principal infections of childhood. PMID- 21032291 TI - The results of routine prophylaxis and treatment of rickets in war-time nurseries. PMID- 21032290 TI - Infantile diarrhoea: An Analysis of 216 Cases with Special Reference to Institutional Outbreaks. PMID- 21032292 TI - Renal dwarfism: A Record of Abnormalities in Carbohydrate Metabolism. PMID- 21032293 TI - Congenital hemi-atrophy. PMID- 21032294 TI - Paroxysmal tachycardia in infancy. PMID- 21032295 TI - Congenital malformation of the heart in one of identical twins. PMID- 21032296 TI - Thomas Barlow, 1845-1945. PMID- 21032297 TI - A Handlist of the Writings of Sir Thomas Barlow. PMID- 21032298 TI - The assessment of health in childhood. PMID- 21032299 TI - The effect of national bread, of iron medicated bread, and of iron cooking utensils on the haemoglobin level of children in war-time day nurseries. PMID- 21032300 TI - The fragility of the red cell to hypotonic saline in infancy and childhood. PMID- 21032301 TI - Toxic thrombocytopenic purpura following local sulphathiazole therapy. PMID- 21032302 TI - The diagnosis of chronic intussusception in children: With an Account of There Cases. PMID- 21032303 TI - Cardiac complications in scarlet fever. PMID- 21032304 TI - Pyelonephritis malignant hypertension and ulceration of small intestine in a child. PMID- 21032305 TI - Congenital thrombocytopenic purpura. PMID- 21032306 TI - Severe and prolonged underfeeding in African children: (The Kwashiorkor Syndrome of Malignant Malnutrition). PMID- 21032307 TI - Penicillin in infections of infancy. PMID- 21032308 TI - Pulse-rate and blood-pressure in infancy and early childhood. PMID- 21032309 TI - Renal venous thrombosis and infarction in the newborn. PMID- 21032310 TI - Bilateral adrenal hypertrophy in infancy. PMID- 21032312 TI - Spontaneous pneumothorax in infancy. PMID- 21032311 TI - Splenomegaly and hepatomegaly in an adolescent simulating Banti's syndrome. PMID- 21032313 TI - Growth and health of Belgian children: During and After the German Occupation (1940-1944). PMID- 21032316 TI - The nature of Still's disease: With Report of a Case. PMID- 21032315 TI - The clinical material of health in paediatrics: Where to Get it, and How to Use it. PMID- 21032314 TI - Infection in infancy. PMID- 21032317 TI - Decrease of serum cholesterol ester in haemolytic disease of the newborn. PMID- 21032318 TI - Osteomyelitis of the jaws in infancy: Treated with Penicillin. PMID- 21032319 TI - The measurement of the nutritional level of thiamin in children by the estimation of the urinary excretion. PMID- 21032320 TI - Idiopathic muscular hypertrophy of oesophagus, pylorus, duodenum and jejunum in a young girl. PMID- 21032321 TI - Cystic fibrosis of the pancreas. PMID- 21032322 TI - The Early Failure of Breast Feeding: A Clinical Study of its Causes and their Prevention. PMID- 21032323 TI - Some Observations on Penicillin: Its Dosage and Administration in Infancy. PMID- 21032324 TI - Aerosol Penicillin in the Oxygen Tent. PMID- 21032325 TI - Penicillin in the Treatment of Neonatal Sepsis. PMID- 21032326 TI - The Sulphonamides in the Treatment of Infections in Infancy. PMID- 21032327 TI - Rickets in Singapore. PMID- 21032329 TI - Case of Congenital Atresia of the Oesophagus with Infantile Pyloric Stenosis. PMID- 21032328 TI - Dwarfism with Retinal Atrophy and Deafness. PMID- 21032330 TI - The Statistics of Prematurity: A Plea for Standardization. PMID- 21032332 TI - The Incidence of Congenital Pyloric Stenosis. PMID- 21032331 TI - Malnutrition in Children under Three Years of Age in Ashanti, West Africa. PMID- 21032333 TI - Dental Fluorosis. PMID- 21032334 TI - Pyocolpos in Infancy. PMID- 21032335 TI - Pulmonary Agenesis and Hypoplasia. PMID- 21032336 TI - A Fatal Case of Beriberi in a Child in England. PMID- 21032337 TI - Penicillin and Sulphonamides in the Treatment of Infections in Infancy. PMID- 21032338 TI - The Psychological Aspect of Allergic Skin Reactions in Childhood. PMID- 21032339 TI - Etiological Aspects of Gastro-Enteritis: Part II. PMID- 21032340 TI - Local Paralysis in Children after Injections. PMID- 21032341 TI - Muscle Spasm in Poliomyelitis: A Study of a New Zealand Epidemic. PMID- 21032342 TI - A Survey of Recent Developments in the Treatment of Pneumococcal Meningitis. PMID- 21032344 TI - Neuro-muscular Incoordination at the Cardia in the Newborn. PMID- 21032343 TI - Protein Requirements of Infants: 3. The Nutrition of Premature Infants. PMID- 21032345 TI - Haemolytic Disease of the Newborn: Part I: A Clinical-Pathological Study of 157 Cases. PMID- 21032346 TI - Hypertension of Renal Origin in Childhood. PMID- 21032347 TI - Epulis in the Newborn. PMID- 21032348 TI - Letterer-Siwe Disease. PMID- 21032349 TI - Meconium Ileus with no Pancreatic Abnormality. PMID- 21032351 TI - Child Welfare Films. PMID- 21032350 TI - The Development of Locomotion. PMID- 21032353 TI - The Development of Manipulation. PMID- 21032352 TI - Memorandum on the Care of Premature Babies in Urban and Rural Areas. PMID- 21032355 TI - Your Children's Play. PMID- 21032354 TI - Surprise Attack. PMID- 21032356 TI - Mandibulofacial Dysostosis in an African Infant. PMID- 21032357 TI - A Case of Idiopathic Pulmonary Haemosiderosis with Myocarditis. PMID- 21032359 TI - The Diagnosis of Mental Retardation in Infancy: A Follow-Up Study. PMID- 21032358 TI - Herpes Simplex Virus Infection: Dissemination in Association with Malnutrition. PMID- 21032360 TI - Acute Intestinal Obstruction due to Mesenteric Lymphangioma. PMID- 21032362 TI - Incubator for Infants Undergoing Surgery. PMID- 21032363 TI - Vesico-intestinal Fissure. PMID- 21032364 TI - Poisoning Accidents in Childhood. PMID- 21032361 TI - The Maintenance of Stability in the Newly Born: Part 2. Thermal Balance. PMID- 21032365 TI - The Cerebro-ocular-renal Dystrophies: a new variant. PMID- 21032366 TI - Aldrich's Syndrome: Familial Thrombocytopenia, Eczema and Infection. PMID- 21032367 TI - Gout and Cerebral Palsy in a Three-year-old Boy. PMID- 21032368 TI - Cortical Atrophy of the Brain in Infants associated with Failure to Thrive. PMID- 21032369 TI - Pancytopenia with Congenital Defects (Fanconi's Anaemia). PMID- 21032370 TI - Congenital Adenomatoid Malformation of Lung with Pneumothorax. PMID- 21032371 TI - The Bacterial Flora of the Stomach and Small Intestine in Children with Intestinal Obstruction. PMID- 21032372 TI - The Oxygen Tension of the Blood in the Umbilical Cord and the Intervillous Space. PMID- 21032373 TI - Absent Umbilical Artery: A Review of 113 Cases. PMID- 21032374 TI - Adrenal Cortical Hypoplasia in Siblings. PMID- 21032375 TI - Disorders of Spoken Language in Young Children. PMID- 21032376 TI - The Effect of Corticotrophin and Prednisolone on Infantile Spasms with Mental Retardation. PMID- 21032377 TI - Observations on the Clinical Course and Treatment of One Hundred Cases of Still's Disease. PMID- 21032378 TI - Functionally Active Intrathoracic Neuroblastoma. PMID- 21032379 TI - A Familial Tubular Absorption Defect of Glucose and Amino Acids. PMID- 21032381 TI - From the Mermaid to Anal Imperforation: The Syndrome of Caudal Regression. PMID- 21032380 TI - Endemic Urinary Lithiasis in Turkish Children: A Clinical Study of 119 Cases. PMID- 21032382 TI - Urinary Tract Duplication in Childhood. PMID- 21032383 TI - Congenital Thrombocytopenic Purpura Treated by Exchange Transfusion. PMID- 21032384 TI - Calcification of the Adrenal Glands in Young Children: A Report of Three Cases with a Review of the Literature. PMID- 21032385 TI - The Effect of a Continuous Intravenous Infusion of Inorganic Phosphate on the Rachitic Lesions in Cystinosis. PMID- 21032386 TI - Familial Ataxia-telangiectasia. PMID- 21032387 TI - Congenital Abnormalities in the African Newborn. PMID- 21032389 TI - Management of the Engstrom Respirator in Early Infancy. PMID- 21032388 TI - Artificial Respiration in Severe Abdominal Disease. PMID- 21032390 TI - Gastrostomy for the Newborn Surgical Patient: A Report of 140 Cases. PMID- 21032391 TI - Importance of Endothoracic Lymph Nodes in Pulmonary Disease in Childhood and Adolescence. PMID- 21032392 TI - Congenital Defects associated with Prematurity. PMID- 21032393 TI - Megaloblastic Anaemia Complicating Dietary Treatment of Phenylketonuria in Infancy. PMID- 21032394 TI - Electroencephalographic and Clinico-pathological Observations in Hydrocephalic Children. PMID- 21032395 TI - Morquio-Ullrich's Disease: An Inborn Error of Metabolism? PMID- 21032396 TI - Prognosis of 'Observation Hip' in Children. PMID- 21032397 TI - Pulmonary Embolism in Children. PMID- 21032398 TI - Renal Size in Normal Children: A Radiographic Study During Life. PMID- 21032399 TI - Myocardial Fibrosis in Fibrocystic Disease of the Pancreas. PMID- 21032400 TI - Congenital Hypoplastic Anaemia: Report of Two Cases. PMID- 21032401 TI - Significance of Extensor Plantar Responses in Muscular Dystrophy. PMID- 21032402 TI - A Controlled Trial of Immediate and Delayed Closure of Spina Bifida Cystica. PMID- 21032403 TI - Infantile Hypoglycaemia due to Inherited Deficiency of Glycogen Synthetase in Liver. PMID- 21032404 TI - Obstructive Jaundice and Haemolytic Disease of the Newborn. PMID- 21032405 TI - A Follow-up Study of Dysmature Infants. PMID- 21032406 TI - Hypophosphatasia in the Newborn. PMID- 21032407 TI - Congenital Tuberculosis and Maternal Sarcoidosis. PMID- 21032408 TI - Neonatal Aplastic Anaemia and Fanconi's Anaemia. PMID- 21032409 TI - Colostomies in Infancy and Childhood. PMID- 21032410 TI - Observations on the Conservative Treatment of Exomphalos. PMID- 21032412 TI - Weights of Children with Major Congenital Abnormalities of the Intestinal Tract. PMID- 21032411 TI - Embryology of Exomphalos and Allied Malformations. PMID- 21032413 TI - Fluid and Electrolyte Requirements of Newborn Infants with Intestinal Obstruction. PMID- 21032414 TI - Management of Tetanus Neonatorum with Intermittent Positive-pressure Respiration. PMID- 21032415 TI - Does Undernutrition During Infancy Inhibit Brain Growth and Subsequent Intellectual Development? PMID- 21032416 TI - Glucose-6-Phosphate Dehydrogenase Deficiency and Neonatal Jaundice. PMID- 21032417 TI - A Study of the Immunoglobulins in Premature Infants. PMID- 21032418 TI - Aldosterone and 17-hydroxycorticosteroid Excretion Following Ramstedt's Operation. PMID- 21032419 TI - The Placental Transfusion Syndrome in Monozygous Twins. PMID- 21032420 TI - Gonadal Dysgenesis with Unusual Abnormalities. PMID- 21032421 TI - Neonatal Jaundice Associated with Familial G6PD Deficiency in Israel. PMID- 21032422 TI - A Reliable Rapid Screening Test for Sulphatide Lipidosis. PMID- 21032423 TI - Neonatal Fits Associated with Hypomagnesaemia. PMID- 21032424 TI - Intellectual Impairment in Muscular Dystrophy. PMID- 21032425 TI - Methods of Routine Haemoglobinometry in Childhood: Evaluation of Copper Sulphate Densitometry. PMID- 21032426 TI - Urinary White Cell Excretion in Childhood. PMID- 21032427 TI - Histological Observations on Glycogen Reserves of the Foetus and Newborn Infant. PMID- 21032428 TI - Venous Pressure Measurement in Exchange Transfusion. PMID- 21032429 TI - An Unusual Case of Subcutaneous Fat Necrosis in a Newly Born Infant. PMID- 21032431 TI - Editorial note. PMID- 21032430 TI - Choledochal Cyst: A Case Report and Discussion of Aetiology. PMID- 21032432 TI - British association of paediatric surgeons. PMID- 21032433 TI - The neurology of cerebral palsy. PMID- 21032434 TI - The immunological system of the child: part I: development of immunity in the child. PMID- 21032435 TI - The Immunological System of the Child: Part II: Immunological Deficiency States. PMID- 21032436 TI - Cranio-facial Dysostosis in a Dorset Family. PMID- 21032437 TI - Clinical and biochemical observations in two cases of hartnup disease. PMID- 21032438 TI - Nalidixic Acid: microbiological and clinical studies on urinary infections in children. PMID- 21032439 TI - Experience with nalidixic Acid in the treatment of urinary tract infections of children. PMID- 21032440 TI - Effect of mepacrine (atebrin) on the success of antibacterial treatment of urinary infections. PMID- 21032441 TI - Inhaled Foreign Bodies in Children: An Analysis of 40 cases. PMID- 21032442 TI - Minimal rates of oxygen consumption in sick and premature newborn infants. PMID- 21032443 TI - Range of critical temperatures in sick and premature newborn babies. PMID- 21032444 TI - Rubella retinopathy: an account of six cases. PMID- 21032445 TI - Serum magnesium levels in the newborn and older child. PMID- 21032446 TI - Treatment of a Phaeochromocytoma with a beta-Adrenergic Blocking Agent. PMID- 21032447 TI - Assessment of gestational age by neurological examination. PMID- 21032449 TI - Treatment-research-experiment? PMID- 21032448 TI - Osmolality as a measure of dehydration in the neonatal period. PMID- 21032450 TI - Dissecting microscope appearance of small bowel mucosa in children. PMID- 21032451 TI - European society for paediatric nephrology foundation meeting. PMID- 21032453 TI - Editorial note. PMID- 21032452 TI - Hyperammonaemia due to ornithine transcarbamylase deficiency. PMID- 21032454 TI - Meeting at Newcastle upon Tyne. PMID- 21032455 TI - The value of blood gas analysis in lower respiratory tract infection in infancy. PMID- 21032456 TI - Regulation of erythropoiesis by stimulators and inhibitors. PMID- 21032457 TI - Standards for Children's Height at Age 2 to 9 years allowing for height of Parents. PMID- 21032458 TI - Pulmonary metastases in wilms. PMID- 21032459 TI - Paediatric implications of the battered child syndrome. PMID- 21032460 TI - Therapeutic trials in wilms' tumour (nephroblastoma) and neuroblastoma. PMID- 21032462 TI - European society for paediatric nephrology. PMID- 21032461 TI - Evaluation of corticosteroids in treatment of tuberculous meningitis. AB - 98 patients with tuberculous meningitis were studied with a view to assessing the value of steroids as an adjuvant to antitubercular drugs. The patients were divided into three groups irrespective of the clinical stage of the disease. One group received antitubercular drugs alone, the second oral prednisolone, and the third intrathecal steroids, in addition to the antitubercular drugs. There was no significant difference in the mortality rate in the different groups. Oral steroid treatment lowered the CSF protein more rapidly, but did not influence the outcome nor prevent the formation of spinal block. PMID- 21032463 TI - Neonatal Society: Meeting on 29 October 1970, at St. Mary's Hospital, London W.2. PMID- 21032464 TI - Meeting held on 4 February 1971 at St. Thomas's Hospital, London S.E.1. PMID- 21032465 TI - Scottish paediatric society. PMID- 21032466 TI - Detection of heterozygotes for homocystinuria by oral loading with L-methionine. PMID- 21032467 TI - Clinical value of plasma creatine kinase and uric acid levels during first week of life. PMID- 21032468 TI - Sweat function in babies with defects of central nervous system. PMID- 21032469 TI - Effect of glucose on plasma glucagon, insulin, and growth hormone levels in exchange transfusions. PMID- 21032470 TI - Meeting held on 4 November 1971 at St. Thomas's Hospital, London S.E.1. PMID- 21032471 TI - Some problems in surgical Management of Children with Hiatus Hernia. PMID- 21032472 TI - Meconium I1eus: Immediate and Long-term Survival. PMID- 21032474 TI - Lower urinary obstruction in infancy: review of lesions and symptoms in 165 cases. PMID- 21032473 TI - Intra-abdominal Injuries in the Battered Baby Syndrome. PMID- 21032475 TI - European society for paediatric nephrology. PMID- 21032477 TI - Nutrition and cellular growth. PMID- 21032476 TI - Meeting held on 3 February 1972 at St. Thomas's Hospital, London S.E.1. PMID- 21032478 TI - Immunological studies in chronic granulomatous candidiasis and the effect of treatment with dialysable transfer factor. PMID- 21032479 TI - Late onset form of globoid cell leucodystrophy. PMID- 21032480 TI - Circadian variation in plasma 17-hydroxyprogesterone in patients with congenital adrenal hyperplasia. PMID- 21032481 TI - Defective aldosterone synthesis: 18-hydroxylase defect. PMID- 21032482 TI - Effect of diet on water intake and urinary solute concentrations in infants. PMID- 21032483 TI - Clinical pharmacology of gentamycin in the newborn. PMID- 21032484 TI - Response to glucagon in small-for-dates hypoglycaemic newborn infants. PMID- 21032485 TI - Editorial note. PMID- 21032487 TI - Meeting held on 18 May 1972 at Sheffield. PMID- 21032486 TI - Proceedings of the forty-third annual meeting. PMID- 21032488 TI - European society for paediatric nephrology. PMID- 21032489 TI - Meeting held on 2 November 1972 at St. Thomas's Hospital London S.E.1. PMID- 21032490 TI - Prophylactic antibiotics in umbilical artery catheterization in the newborn. AB - Over a period of 30 months, umbilical artery catheters were inserted in 229 infants. The main complications were haemorrhage, infection, and obstruction of a blood vessel. The incidence of infection was not affected by the use of prophylactic antibiotics. Vascular obstruction was more common in small infants, and in those in whom a catheter was reintroduced in the same blood vessel. PMID- 21032491 TI - Plasma tocopheral values in infants and children. PMID- 21032492 TI - Neonatal cold injury. PMID- 21032493 TI - Giardiasis and coeliac disease. PMID- 21032494 TI - Meeting held on 1 February 1973 at St. Thomas's Hospital London S.E.1. PMID- 21032495 TI - Meeting held on 1 February 1973 at St. Thomas's Hospital, London S.E.1. PMID- 21032496 TI - Development of mammalian fast muscle: Dynamic and biochemical properties correlated. PMID- 21032497 TI - Pulmonary capillary blood flow in preterm infants with respiratory distress. PMID- 21032498 TI - Observations on lactate and pyruvate concentrations, lactate/pyruvate ratios, and acid-base variables in simultaneously sampled arterial blood and CSF after presumed acute hypoxia in infants and children. PMID- 21032499 TI - Reduced serum sulphation factor in malnourished children. PMID- 21032500 TI - Infant feeding practices and plasma osmolality. PMID- 21032501 TI - Clinical significance of parainfluenza virus infections in children. PMID- 21032502 TI - Surveillance of congenital rubella defects. PMID- 21032503 TI - Aminoglutethimide in the treatment of congenital adrenal hyperplasia. PMID- 21032504 TI - Is the tuberous sclerosis syndrome a rare condition? A study of 100 cases. PMID- 21032505 TI - Incidence of certain behavior symptomas in 295 epileptic schoolchildren compared with matched controls. PMID- 21032506 TI - Febrile convulsions: Factors in recurrence. PMID- 21032507 TI - Meeting held on 28 June 1973 at St. Mary's Hospital, Manchester. PMID- 21032508 TI - European society for paediatric nephrology. PMID- 21032509 TI - Meeting held on 15 November 1973 at St. Thomas's Hospital, London S.E.1. PMID- 21032510 TI - T(4) levels in normal neonates. PMID- 21032511 TI - Assessment of venous admixture in infants with congenital heart disease using arterial blood gas tensions. PMID- 21032512 TI - Experience with use of CPAP in respiratory distress in the newborn. PMID- 21032513 TI - Noninvasive method of continuous measurement of gas exchange in spontaneously breathing infants in a neutral thermal environment. PMID- 21032515 TI - Serum and erythrocyte folate levels in low birthweight infants. PMID- 21032514 TI - Fits in hydrocephalic children. PMID- 21032516 TI - Congenital sternomastoid torticollis: An intrauterine postural deformity. PMID- 21032517 TI - Familial incidence of bifid and double ureters. PMID- 21032519 TI - Meeting held on 7 February 1974 at St. Thomas's Hospital, London S.E.1. PMID- 21032518 TI - Some social aspects of day-case surgery. PMID- 21032521 TI - 50th Meeting held on 28 November 1974 at the Zoological Society, Regent's Park, London. PMID- 21032520 TI - Meeting held on 28 June 1974 at Edinburgh University, David Hume Tower. PMID- 21032522 TI - Fat absorption and weight gain of small babies fed two filled milk formulae. PMID- 21032523 TI - Study of a group of children who initially had convulsions associated with fever and later developed epileptic attacks in the absence of pyrexia. PMID- 21032524 TI - Serum IgG levels in feto-fetal transfusion syndrome. PMID- 21032525 TI - Effect of bronchodilators on respiratory resisance in infants and young children with bronchiolitis and wheezy bronchitis. PMID- 21032526 TI - Spring meeting, southmead hospital, bristol, 21 and 22 march 1975. PMID- 21032528 TI - Spring Meeting held on 6 February 1975 at St. Thomas's Hospital, London. PMID- 21032527 TI - Proceedings of the forty-sixth annual meeting. PMID- 21032529 TI - Paediatric research society. PMID- 21032531 TI - Second joint meeting. PMID- 21032530 TI - Scottish paediatric society. PMID- 21032533 TI - Proceedings of the forty-seventh annual meeting. PMID- 21032532 TI - Spring Meeting, Guy's Hospital, London 26 and 27 March 1976. PMID- 21032534 TI - Scottish paediatric society. PMID- 21032535 TI - Summer Meeting held on 9 July 1976 at the Maternity Hospital, Queen Elizabeth Medical Centre, Birmingham. PMID- 21032536 TI - James spence medallist, 1976 douglas montagu temple gairdner. PMID- 21032537 TI - Tenth annual meeting, barcelona, 30 june to 3 july 1976. PMID- 21032539 TI - Scottish paediatric society. PMID- 21032538 TI - Autumn meeting, southampton general hospital, 24 and 25 september 1976. PMID- 21032540 TI - Paediatric Pathology Society and Developmental Pathology Society: Proceedings of the Twenty-second Annual Meeting. PMID- 21032541 TI - Proceedings of the Forty-eighth Annual Meeting. PMID- 21032542 TI - Spring meeting, university hospital of wales, cardiff, 1 and 2 april 1977. PMID- 21032543 TI - Scottish paediatric society. PMID- 21032544 TI - The british paediatric association, the british medical association, and the archives. PMID- 21032545 TI - Pathogenesis of human muscular dystrophy. PMID- 21032546 TI - Pediatric oncologic radiology. PMID- 21032547 TI - Autumn meeting, cambridge, 16 and 17 september 1977. PMID- 21032549 TI - Pediatric radiology: case studies. PMID- 21032548 TI - Summer Meeting held on 24 June 1977 at the Radcliffe Infirmary and Somerville College, Oxford. PMID- 21032550 TI - Progress in medical virology. PMID- 21032552 TI - Clinics in haematology: perinatal haematology. PMID- 21032551 TI - Proceedings of the Twenty-third Annual Meeting. PMID- 21032554 TI - Recent progress in pediatric endocrinology: proceedings of the serono symposia, vol. 12. PMID- 21032553 TI - The diabetic pancreas. PMID- 21032556 TI - Meeting held on 2 February 1978 at St Thomas's Hospital, London. PMID- 21032555 TI - Child Abuse: Prediction, Prevention and Follow-up. PMID- 21032558 TI - Antimicrobial chemotherapy for newborns: practical application of pharmacology to clinical usage. PMID- 21032557 TI - Scottish paediatric society. PMID- 21032559 TI - Obstetrics and the newborn. PMID- 21032560 TI - Neonatal-perinatal medicine: diseases of the fetus and infant. PMID- 21032561 TI - The year book of pediatrics. PMID- 21032563 TI - Clinical pediatric oncology. PMID- 21032562 TI - Brain dysfunction in infantile febrile convulsions. PMID- 21032564 TI - Intrauterine asphyxia and the developing fetal brain. PMID- 21032565 TI - Diagnosis and primary care of accidents and emergencies in children: a manual for the casualty officer and the family doctor. PMID- 21032566 TI - Prenatal diagnosis of genetic disease. PMID- 21032567 TI - Editorial comment. PMID- 21032568 TI - Care of the Handicapped Child: A Festschrift for Ronald MacKeith. PMID- 21032569 TI - Neonatal medicine. PMID- 21032571 TI - Heart disease in infancy and childhood. PMID- 21032570 TI - Major mental handicap: methods and costs of prevention. PMID- 21032572 TI - Practical paediatric endocrinology. PMID- 21032573 TI - Pediatric neurology and neurosurgery. PMID- 21032574 TI - Increased intracranial pressure in children: diagnosis and treatment. PMID- 21032575 TI - Host defenses in the human neonate. PMID- 21032576 TI - Paediatrics. PMID- 21032577 TI - Rehabilitation of arm amputees and limb-deficient children. PMID- 21032578 TI - Aplastic anaemia. PMID- 21032579 TI - Smith's Blood Diseases of Infancy and Childhood. PMID- 21032581 TI - New editor of the Archives. PMID- 21032580 TI - Proceedings of the Fifty-first Annual Meeting. PMID- 21032582 TI - British paediatric association: standing ethics advisory committee. PMID- 21032583 TI - Scottish paediatric society. PMID- 21032584 TI - Multiple choice questions on paediatrics. PMID- 21032585 TI - Paediatric orthopaedics and fractures. PMID- 21032587 TI - Infants born at risk: behaviour and development. PMID- 21032586 TI - A scheme of paediatric neurological investigation. PMID- 21032588 TI - Advances in perinatal neurology. PMID- 21032589 TI - Meeting held on 8 November 1979 at the Institute of Child Health, London. PMID- 21032590 TI - Paediatric chemical pathology. Clinical tests and reference ranges. PMID- 21032591 TI - James spence medallist, 1980. PMID- 21032592 TI - With commentary. PMID- 21032593 TI - With commentary. PMID- 21032594 TI - Neonatal society. PMID- 21032595 TI - Proceedings of the Fifty-second Annual Meeting. PMID- 21032597 TI - Et alia. PMID- 21032596 TI - Follow-up of the High Risk Newborn: A Practical Approach. PMID- 21032598 TI - Sheffield, 28 and 29 march 1980. PMID- 21032599 TI - Scottish paediatric society. PMID- 21032600 TI - With commentary. PMID- 21032602 TI - Meeting held on 4 July 1980 in Southampton. PMID- 21032601 TI - With commentary. PMID- 21032603 TI - Making music with the young handicapped child: a guide for parents. PMID- 21032604 TI - Helping clumsy children. PMID- 21032605 TI - Breath-holding attacks-Dickens 1864. PMID- 21032606 TI - The challenge of urinary tract infections. PMID- 21032607 TI - Publication will be quicker. PMID- 21032609 TI - James spence medallist, 1981. PMID- 21032608 TI - Infectious diseases of children. PMID- 21032610 TI - With commentary. PMID- 21032611 TI - With commentary. PMID- 21032612 TI - Pediatric and adolescent echocardiography. PMID- 21032614 TI - Proceedings of the Fifty-third Annual Meeting. PMID- 21032613 TI - With commentary. PMID- 21032616 TI - Amniotic fluid and its clinical significance. PMID- 21032615 TI - Encouraging language development. PMID- 21032617 TI - Shorter notices. PMID- 21032618 TI - With commentary. PMID- 21032619 TI - Editor's comment. PMID- 21032620 TI - Control of growth. PMID- 21032621 TI - Handbook of neonatal intensive care. PMID- 21032623 TI - Looking back. PMID- 21032622 TI - An editor departs. PMID- 21032625 TI - A new editor. PMID- 21032624 TI - The battered child. PMID- 21032626 TI - Childhood cancer in britain: incidence, survival, and mortality. PMID- 21032627 TI - A colour atlas of ear disease. PMID- 21032629 TI - MCQ's in paediatrics. PMID- 21032628 TI - With commentary. PMID- 21032630 TI - Evaluation of transcutaneous oxygen monitors. PMID- 21032631 TI - Current pediatric therapy 10. PMID- 21032633 TI - Paediatric urology. PMID- 21032632 TI - Handbook of behavioral pediatrics. PMID- 21032634 TI - Postoperative pediatric uroradiology. PMID- 21032635 TI - Paediatric handbook. PMID- 21032636 TI - With commentary. PMID- 21032638 TI - Common symptoms of diseases in children. PMID- 21032637 TI - Scottish paediatric society and british paediatric association. PMID- 21032639 TI - Understanding child abuse. PMID- 21032640 TI - Textbook of paediatric nutrition. PMID- 21032642 TI - Metabolic adaptation to extrauterine life: the antenatal role of carbohydrates and energy metabolism. PMID- 21032641 TI - Editorial. PMID- 21032643 TI - Basic Developmental Screening: 0-4 years. PMID- 21032644 TI - A bedtime story. PMID- 21032645 TI - With commentary. PMID- 21032646 TI - Paediatric emergencies: a practical guide to acute paediatrics. PMID- 21032648 TI - Editorial. PMID- 21032647 TI - Myocardial Infarction at Young Age: International Symposium held in Bad Krozingen, 30-31 January 1981. PMID- 21032649 TI - Organic acids in man: analytical chemistry, biochemistry, and diagnosis of the organic acidurias. PMID- 21032650 TI - Symposium on pediatric plastic surgery: vol. 21. Proceedings of the symposium of the plastic surgery educational foundation of the american society of plastic and reconstructive surgeons incorporated, chicago, illinois, 19-21 october 1979. PMID- 21032651 TI - Toys and play for the handicapped child. PMID- 21032653 TI - Treatment of cerebral palsy and motor delay. PMID- 21032652 TI - Craig's Care of the Newly Born Infant. PMID- 21032654 TI - A practical approach to pediatric endocrinology. PMID- 21032655 TI - With commentary. PMID- 21032656 TI - Respiratory illness in children. PMID- 21032657 TI - Neuroblastoma: clinical and biological manifestations. PMID- 21032658 TI - Urinary tract infections in children. PMID- 21032660 TI - Paediatric emergencies. PMID- 21032659 TI - The diagnosis and primary care of accidents and emergencies. PMID- 21032662 TI - Nutrition in health and disease and international development. PMID- 21032661 TI - Clinics in endocrinology and metabolism. PMID- 21032663 TI - Practical gamuts and differential diagnosis in paediatric radiology. PMID- 21032664 TI - James spence medallist 1983. PMID- 21032665 TI - Core textbook of paediatrics. PMID- 21032666 TI - Topics in gastroenterology 10. PMID- 21032667 TI - Sleep management manual. PMID- 21032668 TI - Proceedings of the annual general meeting. PMID- 21032669 TI - Scientific proceedings. PMID- 21032671 TI - Editorial. PMID- 21032670 TI - The effects of maternal alcohol and drug abuse on the newborn. PMID- 21032672 TI - With commentary. PMID- 21032673 TI - With commentary. PMID- 21032674 TI - An atlas of oxygen-cardiorespirograms in newborn infants. PMID- 21032675 TI - The normal child-some problems of the early years and their treatment. PMID- 21032676 TI - Getting through to your handicapped child: a handbook for parents, foster parents, teachers, and anyone caring for handicapped children. PMID- 21032677 TI - Lead versus health: sources and effects of low level lead exposure. PMID- 21032678 TI - 1983 year book of paediatrics. PMID- 21032679 TI - Atlas of human prenatal morphogenesis. PMID- 21032680 TI - Prevention of Spina Bifida and other Neural Tube Defects. PMID- 21032681 TI - Pediatric neurology. PMID- 21032682 TI - Acute shortage of children's nurses. PMID- 21032684 TI - Basic child psychiatry. PMID- 21032683 TI - Infections in children. PMID- 21032685 TI - Oral orthopaedics and orthodontics for cleft lip and palate. PMID- 21032686 TI - Drugs and pregnancy: human teratogenesis and related problems. PMID- 21032687 TI - Principles of paediatric fluid therapy. PMID- 21032688 TI - Children's Fractures. PMID- 21032689 TI - With commentary. PMID- 21032690 TI - With commentary. PMID- 21032691 TI - Diabetes and the Endocrine Pancreas: A biochemical Approach. PMID- 21032693 TI - Skeletal dysplasia. PMID- 21032692 TI - Textbook of paediatric emergency medicine. PMID- 21032694 TI - Multiple choice questions on paediatrics. PMID- 21032695 TI - Nelson textbook of paediatrics. PMID- 21032696 TI - Pediatrics and adolescent endocrinology: vol 12. Evaluation of growth hormone secretion. PMID- 21032697 TI - Neonatal kidney and fluid electrolytes. PMID- 21032698 TI - Centile values of birthweight for gestational age in Scottish infants. PMID- 21032700 TI - A colour atlas of clinical genetics. PMID- 21032699 TI - Clinics in haematology: vol 12. The spleen. PMID- 21032702 TI - The paediatric chest: radiological, clinical, and pathological observations. PMID- 21032701 TI - Sunday after the war. PMID- 21032703 TI - Care of severely malformed infants. PMID- 21032704 TI - Betes noires. PMID- 21032705 TI - Colour atlas of paediatric haematology. PMID- 21032706 TI - The development of the infant and young child: normal and abnormal. PMID- 21032707 TI - The international congress of paediatrics and the international paediatric association. PMID- 21032708 TI - With commentary. PMID- 21032709 TI - Working party on chronic disability in childhood and adolescence. PMID- 21032710 TI - Medical meetings. PMID- 21032711 TI - A colour atlas of the newborn. PMID- 21032712 TI - Atlas of two-dimensional echocardiography in congenital cardiac defects. PMID- 21032713 TI - Biology of vitamin e: ciba foundation symposium 101. PMID- 21032714 TI - Workbook in practical neonatology. PMID- 21032715 TI - Advances in Epileptology: The XIVth Epilepsy International Symposium. PMID- 21032716 TI - Clinical examination of children: a handbook. PMID- 21032717 TI - Topics in paediatric nutrition. PMID- 21032718 TI - Abstracts-false science. PMID- 21032720 TI - Nutritional adaptation of the gastrointestinal tract of the newborn. PMID- 21032719 TI - Risk factors in pregnancy and disease of the fetus and newborn. PMID- 21032722 TI - Henry kempe. PMID- 21032721 TI - Developmental Pharmacology: Proceedings of a Symposium held in Toronto, October 3 6, 1982. PMID- 21032723 TI - Case presentations in paediatrics. PMID- 21032724 TI - Brain tumours in children: principles of diagnosis and treatment. PMID- 21032725 TI - With commentary. PMID- 21032726 TI - A patient's view of diabetes. PMID- 21032727 TI - With commentary. PMID- 21032729 TI - With commentary. PMID- 21032728 TI - With commentary. PMID- 21032731 TI - Ophthalmic services for children. PMID- 21032730 TI - A touch on the tiller. PMID- 21032732 TI - Lest we forget. PMID- 21032734 TI - Training for terminal cancer care. PMID- 21032735 TI - Joint planning of training grade numbers. PMID- 21032733 TI - Minutes. PMID- 21032736 TI - Categories of babies requiring neonatal care. PMID- 21032737 TI - Comment: Children's doctors and children's teachers share a common cause. PMID- 21032738 TI - Children in care. PMID- 21032739 TI - Warnock committee. PMID- 21032740 TI - Problems facing women who seek a career in paediatrics. PMID- 21032741 TI - Minutes of the annual general meeting. PMID- 21032743 TI - Perinatal care. PMID- 21032742 TI - Training for paediatrics with a special interest in respiratory disease. PMID- 21032744 TI - The numbers game. PMID- 21032745 TI - The inquest. PMID- 21032746 TI - Community nursing review. PMID- 21032747 TI - Working party on cystic fibrosis. PMID- 21032748 TI - The laws of Murfitt. PMID- 21032749 TI - Overseas doctors' training. PMID- 21032750 TI - 12 articles of 1926. PMID- 21032751 TI - For wrapping the fish and chips. PMID- 21032753 TI - A year to remember. PMID- 21032752 TI - Archives and the BPA. PMID- 21032754 TI - With commentary. PMID- 21032756 TI - Minutes of the annual general meeting. PMID- 21032755 TI - Case conferences for child abuse. PMID- 21032757 TI - Future development of the public health function and community medicine. PMID- 21032758 TI - An editor departs. PMID- 21032759 TI - A new editor. PMID- 21032760 TI - Hospital medical staffing. PMID- 21032763 TI - The Journal develops. PMID- 21032761 TI - Minutes of the annual general meeting. PMID- 21032764 TI - Manchester. PMID- 21032765 TI - Primary health care. PMID- 21032766 TI - Neighbourhood nursing. PMID- 21032767 TI - Paediatric training in the United Kingdom. PMID- 21032768 TI - Paediatric intensive care. PMID- 21032769 TI - The British Paediatric Association: 60 years. PMID- 21032770 TI - Medical staffing in paediatric departments in district general hospitals. PMID- 21032771 TI - Medical and nurse staffing for newborn care. PMID- 21032772 TI - The British Paediatric Association: 60 years. PMID- 21032773 TI - Training in community paediatrics. PMID- 21032775 TI - Randomised trials and ribavirin. PMID- 21032774 TI - A gem of a book. PMID- 21032776 TI - Minutes of the annual general meeting. PMID- 21032777 TI - Style matters. PMID- 21032778 TI - Personal choice. PMID- 21032780 TI - British paediatric association diamond jubilee service. PMID- 21032779 TI - British paediatric association. PMID- 21032781 TI - Monitoring blood oxygen (1957): Blood oxygen studies in premature infants. PMID- 21032783 TI - Editorial. PMID- 21032782 TI - Minutes of AGM. PMID- 21032784 TI - Sister journals-the Soviet Union. PMID- 21032786 TI - Latent coeliac disease. PMID- 21032785 TI - European journal of pediatrics. PMID- 21032787 TI - Risk to SIDS siblings. PMID- 21032788 TI - Racial differences in SIDS. PMID- 21032789 TI - Junior staffing cuts in paediatrics-American style. PMID- 21032790 TI - Phenobarbitone is a depressing drug. PMID- 21032791 TI - Severe neonatal respiratory failure. PMID- 21032792 TI - Acta paediatrica japonica. PMID- 21032794 TI - Pediatria polska. PMID- 21032793 TI - Progress of a paper. PMID- 21032795 TI - Journal of pediatrics. PMID- 21032796 TI - Pediatrics. PMID- 21032797 TI - Equipment requirements for community based paediatric oxygen treatment. PMID- 21032799 TI - Acta paediatrica scandinavica. PMID- 21032798 TI - American journal of diseases of children. PMID- 21032800 TI - Outcome measurements for child health. PMID- 21032802 TI - Physical signs of sexual abuse in children. PMID- 21032801 TI - Pediatric research. PMID- 21032803 TI - James spence medallist 1992: professor richard w smithells. PMID- 21032804 TI - The journal develops. PMID- 21032805 TI - Training video: the biology, development and care of twins, triplets and more. PMID- 21032806 TI - Professor Dame June Lloyd. PMID- 21032807 TI - Recent advances in paediatrics 11. PMID- 21032808 TI - McCance and Widdowson - A Scientific Partnership of 60 Years. PMID- 21032809 TI - Food and food additive intolerance in childhood. PMID- 21032810 TI - The practice of medicine in adolescence. PMID- 21032811 TI - Pediatric infectious diseases. PMID- 21032812 TI - Multiple congenital anomalies. A diagnostic compendium. PMID- 21032813 TI - An atlas of clinical syndromes. A visual aid to diagnosis. PMID- 21032814 TI - Pregnancy diabetes and birth. A management guide. PMID- 21032815 TI - Caffey's Pediatric X-Ray Diagnosis: An Integrated Imaging Approach. PMID- 21032816 TI - Pediatric clinical skills. PMID- 21032818 TI - Paediatric emergency medicine. PMID- 21032817 TI - Handbook of pediatric epilepsy. PMID- 21032819 TI - Referee's comments and responses from Dr Alan Watson (convenor). PMID- 21032820 TI - Managing children with psychiatric problems. PMID- 21032821 TI - Cystic fibrosis - current topics. PMID- 21032823 TI - Child Abuse and Neglect. A Clinician's Handbook. PMID- 21032822 TI - Textbook of paediatrics with special reference to problems of child health in developing countries. PMID- 21032824 TI - Child and adolescent psychiatry. PMID- 21032826 TI - Rett syndrome - clinical and biological aspects. PMID- 21032825 TI - Pediatric gastrointestinal disease: pathophysiology, diagnosis, management. PMID- 21032828 TI - Multiple choice questions in dermatology. PMID- 21032827 TI - Notes for the DCH. PMID- 21032829 TI - Synopsis of paediatrics. PMID- 21032831 TI - Welcome to a new editor. PMID- 21032830 TI - An Editor retires. PMID- 21032833 TI - Lucina. PMID- 21032832 TI - Lucina. PMID- 21032835 TI - The inherited metabolic diseases. PMID- 21032834 TI - Lucina. PMID- 21032836 TI - Children as research subjects: science, ethics and law. PMID- 21032837 TI - Children first. PMID- 21032838 TI - Epilepsy in children. PMID- 21032839 TI - Neonatology and clinical chemistry. PMID- 21032840 TI - Diseases of infection. PMID- 21032841 TI - Liver disorders in childhood. PMID- 21032843 TI - Motor development in early and later childhood: longitudinal approaches. PMID- 21032842 TI - Fetal and neonatal pathology. PMID- 21032845 TI - James spence medallist 1996: professor sir david hull. PMID- 21032844 TI - Lucina. PMID- 21032846 TI - Violent video games and young people. Experts are divided about the potential harm, but agree on some steps parents can take to protect children. PMID- 21032847 TI - Cognitive enhancement therapy for schizophrenia. Used early on, this hybrid therapy may improve mental and social functioning. PMID- 21032848 TI - Managing dental phobia. It is best to combine several psychological strategies. PMID- 21032849 TI - Second-step treatments for adolescent depression. The TORDIA study suggests options when initial drug treatment fails. PMID- 21032850 TI - Advice about living with bipolar disorder. PMID- 21032851 TI - Ask the doctor. Is it true that some antidepressants might cause cataracts? PMID- 21032852 TI - [Intervention and representation of poverty]. AB - Any intervention against poverty is not so much an administrative process as a social relation between categories of actors that are partly defined by it. Being a social action, it implies a construction of meaning that will guide the behavior of the actors. This semantic network needs an interpretation. This article presents a simplified model (an "ideal-type") of this meaningful interaction. It will contrast the way the professional actors of the poverty field present poverty and poor people and the way poor people themselves present their situation and the difficulties they face. This comparison will show the great distance between these discourses. PMID- 21032853 TI - [Social-professional status, identity, social participation and media utilization. Analysis of a complex dynamics]. AB - This article examines the link between the domain and level of occupation, on the one hand, and use of media, including internet, on the other. It adds to this investigation an analysis of identity in its relation to media use and accessibility. It challenges the hypothesis of a strong correlation between level of occupation and use and accessibility to media. It reveals complex phenomena of social homogenization and differentiation. Data is extracted from a sample of workers who completed a questionnaire which focused on use of media. PMID- 21032854 TI - [Urban culture and physical and sports activities. The "sportification" of parkour and street golf as cultural mediation]. AB - The article explores the process of "sportification"--i.e., processing physical activity in a sport regulated by a set of rules and standards, legitimized by supervisory institutions--from two originals practices, parkour and urban golf. To study these practices, we crossed the contributions of urban sociology and of the contemporary sociology of sport while respecting the methodological principles of qualitative sociology. A first point concerns the process of"sport" itself, its definition, its various stages, and the role played by communication of stakeholders on public space. The cultural mediation shows us how to institutionalize the movement that represents the "sports" resulted in the same time reconfiguration of physical practices themselves. Recent events illustrate the ongoing reconfiguration, we will detail them. Finally, we show the effects produced by the process on the definition of urban culture and sports: setting sight of activities, enhanced cooperation with the media-cultural, polarization between different types of practical in the case of parkour, around a confrontation between two of the founders. PMID- 21032855 TI - [Chinese medical books and medicine in Japan, Korea and Vietnam]. PMID- 21032856 TI - [Medical studies and practice of the Mito Clan]. PMID- 21032857 TI - [An examination of "Minamata disease general investigation and research liaison council"--The process of making uncertain the organic mercury causal theory]. AB - Minamata disease occurred because inhabitants consumed the polluted seafood. The official confirmation of Minamata disease was in 1956. However, the material cause of that disease was uncertain at that time. The Minamata Food Poisoning Sub committee, under authority of the Food Hygiene Investigation Committee of the Ministry of Health and Welfare, determined the material cause of Minamata disease to be a certain kind of organic mercury in 1959. The sub-committee was dissolved after their report. The discussion about the investigation of the cause was performed in a conference initiated by the Economic Planning Agency, which was titled "Minamata Disease General Investigation and Research Liaison Council". The Participants were eight scientists; four fishery scientists, two chemists, and only two medical scientists, which implied that only examination of the organic mercury was to be discussion. The conference was held four times from 1960 to 1961. In the first and second conferences, the organic mercury research from a medical perspective progressed in cooperation with fishery sciences. In the third conference, it was reported that UCHIDA Makio, professor of Kumamoto University, had found organic mercury crystal in the shellfish found in Minamata-bay. Authorities of biochemistry and medicine in the third conference criticized UCHIDA's research. At the fourth conference, reports contradicting his research were presented. Although those anti-UCHIDA reports were not verified, AKAHORI Shiro, the highest authority of biochemistry, not only accepted them, but also expressed doubt in the organic mercury causal theory. Therefore, this theory was recognized as uncertain. PMID- 21032858 TI - [From Andalusia to Selesia. Development of modern nursing care exemplified by the schlesischen Congregation of Sisters of Holy Elisabeth]. PMID- 21032859 TI - [Architectural aspects of Breslau hospitals exemplified by the All Saints Urban General Hospital]. PMID- 21032860 TI - ["Tradition obligates"]. PMID- 21032861 TI - [From epidemic hospital to university clinic. The Berlin Charite 1710 to 1885]. PMID- 21032862 TI - [From Koppen's indigent cemetery to Berlin Moabit. 175 years construction construction history of Berlin Forensic medicine]. PMID- 21032863 TI - ["We saw our patients waving for a long time". Displacement strategies in the introduction public hospital nursing education in East Germany exemplified by the Deaconess Seminar]. PMID- 21032864 TI - [Evaluation of the Pediatric University Clinic in Bad Altheide (Polanica-Zdroj) to Illertissen]. PMID- 21032865 TI - [Hydrotherapy. From Silesia beginnings to enduring popularity]. PMID- 21032866 TI - [Convents, hospices, hospitals and university clinics. Lisabon health care from secular until today]. PMID- 21032867 TI - [What has changed in therapy of vascular patients (role of statins and beta adrenoblockers)]. AB - Systematised herein are the results of large-scale randomized studies, as well as own findings regarding the use of beta-adrenoblockers and statins in vascular patients. Administration of selective beta-adrenoblockers and statins appeared to decrease the cardiac-complication rate in this cohort of patients. PMID- 21032868 TI - [Peculiarities of antithrombotic treatment in exacerbation of coronary heart disease and transcutaneous coronary interventions in patients suffering from atrial fibrillation and taking vitamin K antagonists (literature review)]. AB - The review analyses various approaches to management of patients presenting with atrial fibrillation and having to take vitamin K agonists in order to prevent arterial thromboembolic complications in cases they develop exacerbations of their coronary hear disease and/or require transcutaneous coronary interventions. With the problem being insufficiently studied as yet, the majority of therapeutic decisions as to the most efficient and safe methods of administering antithrombotic agents in the clinical situations involved are made based on the results of follow up of the patients, the data regarding peculiarities of the action of therapeutic agents, and common sense. Presented herein are contemporary recommendations on long-term antithrombotic therapy in patients suffering from atrial fibrillation and taking vitamin K antagonists and subjected to coronary stenting. PMID- 21032869 TI - [Rheumatic diseases and atherosclerosis: a role of rheological and microcirculatory impairments]. AB - The lecture deals with the present-day views on the role of an inflammatory component in the development of atherosclerosis and accelerated formation of atherosclerotic lesions in autoimmune-aetiology vasculitis syndromes characteristic of rheumatic diseases. Both processes are typically manifested by lesions of the vascular wall in the form of inflammation, thrombosis, necrosis, and subsequent sclerotic alterations. The common links of the pathogenesis of these processes are associated with immune-system impairments, rheological and microcirculatory disorders, endothelial dysfunction, atherosclerosis, and dyslipoproteidaemia. PMID- 21032870 TI - [Parameters of perfusion pulmonoscintigraphy and radionuclide tomoventriculography in non-massive thromboembolism of pulmonary-artery branches]. AB - OBJECTIVE: The present work was aimed at identifying the most informative parameters of perfusion pulmonoscintigraphy and radionuclide tomoventriculography in non-massive thromboembolism of the pulmonary-artery branches. MATERIALS AND METHODS: We examined a total of fifty-five patients. The Study Group was composed of 40 subjects (mean age 60.3 +/- 10.4 years) presenting with non-massive pulmonary artery thromboembolism (PATE). The Comparison Group comprised 15 patients with coronary heart disease (CAD) (average age 59.0 +/- 9.0 years, NYHA functional class I-IT circulatory insufficiency). All patients were subjected to perfusion-ventilatory pulmonoscintigraphy and radionuclide equilibrium tomoventriculography. The basic systolic and diastolic parameters of the right ventricle (RV) were determined using the obtained RESULTS: The Group of patients with non-massive PATE (i. e., damage to the pulmonary vascular bed up to 50%) turned out hypertension. quite heterogeneous by the severity degree of the RV contractility dysfunction. This Group included the patients with and without signs of RV contractility dysfunction. Taking into consideration small extension of the lesion, normal values of functional capability of the right portions of the heart may be interpreted as a sign of acute PATE, whereas the presence of pronounced systolicdiastolic dysfunction of the right ventricle should be regarded as apathognomonic sign of chronicpost-thromboembolic pulmonary hypertension. CONCLUSIONS: The most informative scintigraphic signs of right ventricular dysfunction in thromboembolism of the pulmonary-artery branches are as follows: a decrease in the RV stroke volume, peak ejection rate and filling rate which are revealed even in insignificant embolisation of the lesser circulation vessels. The preserved functional ability of the right portions of the heart in patients with a small scope of damage to the vascular bed of the lungs may be regarded as a sign of acute thromboembolism, while systolic diastolic dysfunction of the right ventricle as one of the indices of chronic post-thromboembolic pulmonary hypertension. PMID- 21032871 TI - [Repeat endovascular interventions after transjugular intrahepatic portosystemic shunt (tips) procedures]. AB - The authors share their experience with transjugular intrahepatic portosystemic shunt (TIPS) procedures preformed in a total of fifty-nine patients diagnosed with and hence operated on for class B and C hepatocirrhosis (according to the Child-Turcotte-Pugh classification), portal hypertension, grade 3 varicosely dilated oesophageal veins, or ascites. Of these, there were 12 women and 47 men (average age 56.3 years). Three types of stents were used: matrix stents (PERICO), self-expanding (ZA-stents, OptiMedsinus-SuperFlex- Visualstents, Zilverstents, SMART), and coated self-expanding stents (Gore Viatorr TIPS Endoprosthesis). Six (11 %) TIPS procedures ended in failure. Of the remaining 53 successful TIPS attempts, thirteen patients developed an in-stent thrombosis at various terms postoperatively, with one patient having experienced it twice Within four postoperative days, thrombosis occurred in three patients, at terms varying from one month to three months in five patients, and from 6 to 12 months in a further five patients. More often thromboses were encountered with the matrix stents (n = 3) 23.0% (PERICO) and self-expanding stents (n = 8) in 61.0% (OptiMed sinus-SuperFlex-Visual). Thromboses were clinically manifested by oesophageal variceal haemorrhage. An in-stent thrombosis was confirmed by means of ultrasonographic duplex scanning (lack of arterial blood flow). The primary stent patency rate following TIPS procedures amounted to 67%. with the secondary assisted graft patency rate equalling 89%. Restoration of the stent's lumen after TIPS procedures by means of endovascular recanalization, rheolytic thrombectomy, balloon angioplasty, and a stent-in-stent technique appears to be a minimally invasive, rather efficient method and virtually the only way to preserve the stent's patency. This technique makes it possible to decrease the rate of recurrent oesophageal variceal haemorrhage. PMID- 21032872 TI - [Clinical aspects of uterine artery embolization efficacy in uterine myomas]. AB - The authors have for the first time evaluated efficacy of embolization of the uterine arteries in uterine myomas depending on peculiarities of the blood flow in the system of the uterine arteries in the context of the B. B. Mandelbrot fractal proportionality. PMID- 21032873 TI - [Quality of life in women with small pelvic varicosity]. AB - We surveyed a total of one hundred and ninety women presenting with small pelvic varicose veins (SPVIV). The chronic pelvic pain syndrome (CPPS) was revealed in nearly a quarter of the examined patients (24.7 %). The women's quality of life was assessed using the SF-36 questionnaire as a more integrative parameter, having demonstrated that women presenting with SPVV had a substantial decrease in all the components of both physical health and mental well-being. The obtained findings have strongly suggested the necessity of carrying out secondary prevention in women suffering from SPVV, even if there are no clinically pronounced manifestations of the disease. PMID- 21032874 TI - [Functional venous insufficiency: diagnosis and treatment (literature review) (Part I)]. AB - Reviewed herein are the available literature data concerning functional venous insufficiency (phlebopathies). Part I analyses the data on terminology, epidemiology, effect on quality of life, aetiology and pathogenesis, risk factors, as well as possible methods of diagnosis of this pathological condition. METHOD: search in the MEDLINE database by means of the PubMed system. PMID- 21032875 TI - [Intraabdominal pressure alterations in ruptured abdominal aortic aneurysms]. AB - The authors investigated the dependence of intraabdominal pressure on the volume of a retroperitoneal haematoma. The study included a total of thirty-four patients in whom elevation of intraabdominal pressure had solely been caused by haemorrhage into the retroperitoneal space. The volume of the retroperitoneal haematoma was calculated based on the findings of spiral computed tomography, whereas intraabdominal pressure was measured using the methods suggested by Sugrue M. and Kron I. L. The statistical analysis showed a moderate positive correlation between the retroperitoneal haematoma volume and the level of intraabdominal pressure. With the volume of the retroperitoneal haematoma approximating to 2,000 ml, intraperitoneal pressure was at the upper limit of the norm. Of the patients examined, none turned out to have developed the high intraperitoneal pressure syndrome. PMID- 21032876 TI - [Remote results of using "ECOFLON" prostheses in management of patients with Leriche's syndrome]. AB - The authors analysed the outcomes of 476 reconstructions performed on the aortofemoral segment for Leriche's syndrome using polytetrafluoroethylene grafts "ECOFLON" within the time frame from 1997 to 2007. The in-hospital mortality rate amounted to 2.7%, thrombosis rate to 0.46%, and amputation rate to 0.69%. The remote results were assessed at follow-up terms varying from 6 to 108 months, with the mean follow-up time thus amounting to 34.6 +/- 1.3 months. Secondary graft patency by the first postoperative year amounted to 98.0 +/- 0.62%, by 5 years to 92.5 +/-1.9%, and by 9 years to 91.4 +/- 1.9%, with primary graft patency being 97.3 < or =0.23%, 84.9 +/- 2.9%, and 82.9 +/- 3.5%, respectively. The limb salvage rate amounted to 97 +/-0.6% after 1 year, equalling 91.2< or =2.2% after 5 years, and 80.9 +/- 5.2% after 9 years. Infection of prosthetic grafts occurred in 1.04% of cases (0.42% in the short-, and 1.05 % in the long term periods). Pseudoaneurysms of distal anastomoses were observed in 0.34% of cases. Analysing two time intervals (i. e., 1997-2002 and 2003-2007) howed a statistically significant betterment of the patency rates (with primary graft patency having increased by 5.3% and secondary graft patency by 5.8%, (P < 0.01), thus apparently suggesting improved quality of explants. It was concluded that polytetrafluoroethylene grafts "ECOFLON" comply with the present-day standards of quality. PMID- 21032877 TI - [Infectious complications of reconstructive operations on carotid arteries in atherosclerotic stenoses]. AB - Analysed herein are the outcomes of a total of 2,240 reconstructive operations on carotid arteries (CA) performed in patients presenting with CA stenosis. Twenty two (0.98%) patients were found to have developed infectious complications with the involvement of the reconstructed zone. Once suppuration had occurred sixteen patients were subjected to autovenous prosthetic repair of the internal carotid artery (ICA), with a further four cases having endured prosthetic reconstruction with a portion of the external CA, and the remaining two patients sustained ligation of the ICA. In the immediate postoperative period, two deaths had occurred, with recurrent infections accompanied and followed by the development of arrosive haemorrhage observed in two cases. The most commonly encountered microbial agents responsible for suppuration were largely staphylococci and streptococci, as well as Escherichia coli. The preoperative and postoperative prevention with antibiotics is obligatory. In order to assess the condition of the carotid arteries and involvement thereof into the infectious process it is necessary to rely upon the findings of ultrasonographic scanning of soft tissues of the neck in a combination with duplex scanning of carotid arteries. Early aggressive surgical policy consisting in extended surgical debridement of the infectious wound, reconstruction of the CA with autologous tissue aimed at preserving cerebral blood supply, and targeted antibiotic therapy make it possible in the majority of cases to obtain positive therapeutic outcomes. PMID- 21032878 TI - [Therapeutic decision-making in patients with stenoses of the extracranial portion of the carotid arteries]. AB - The article is dedicated to the problem concerning the choice of treatment for carotid stenoses, which is becoming yet increasingly important due to revision of the therapeutic approaches to management of stenoses of the extracranial portions of the carotid arteries over the last two decades. Presented herein is a review of the published studies and discussed are possible causes of contradictory findings obtained therein. Separately considered is an economic component of the problem involved, underlining the lack of commonly accepted and expressly defined recommendations on treatment decisions regarding revascularization of the carotid arteries. A conclusion is drawn on the necessity of developing a scientifically based therapeutic algorithm. PMID- 21032879 TI - [Perioperative complications rate depending upon the method of anaesthesia in surgical management of an atherosclerotic lesion of the infrarenal aortic portion]. AB - We examined a total of two hundred and thirty-seven 54-to-69-year-old patients subjected to aortofemoral bypass grafting for atherosclerosis of the aorta and its branches. Depending on the method of anaesthesia, the patients were subdivided into 3 groups: Group One patients received NLA with artificial lung ventilation (ALV), Group Two comprised the patients subjected to surgery in the setting of epidural anaesthesia at the level of ThXII-LI with ALV, and Group Three consisted of the patients who sustained the procedure of thoracic epidural anaesthesia at the level of ThX-Thl with ALV. The groups of patients were representative. The highest and most stable parameters of the coronary blood flow and central haemodynamics turned out to be in patients given thoracic epidural anaesthesia (ThX-Thl) with ALV due to low doses of a topical anaesthetic combined with a narcotic analgesic. The blockade of the sympathetic trunk ensured the highest and most stable parameters of the coronary circulation, stroke index, and ejection fraction as compared with those in the rest groups of patients. PMID- 21032880 TI - [Variants of surgical management for severe arterial hypertension combined with type 2 diabetes mellitus]. AB - Based on studying venous trunks and their syntopia, previously performed on a total of 160 cadavers we elaborated" methods of "cross" shunting. Clinical application thereof in ten patients presenting with severe arterial hypertension accompanied by type 2 diabetes mellitus made it possible to decrease both mortality and complication rates. PMID- 21032881 TI - [Role of vascular surgery by experience of the Great Patriotic War (1941-45) (To the 65th anniversary of the Victory in the Great Patriotic War)]. AB - During the Great Patriotic War, military medicine gained a wide and versatile experience in organization of rendering medical care for and treatment of millions of the wounded in exceptionally complicated circumstances. The most important mission encountered by the medical service, i. e., salvation and treatment of soldiers was accomplished with honour: more than 72.3% of the wounded and 90.6% of diseased soldiers and officers were returned to the ranks by the Russian medical profession. Soviet surgeons contributed significantly to solving problems of field surgery as a whole and vascular surgery in particular. PMID- 21032882 TI - [A case of successful surgical treatment of a patient with portal hypertension and ascites induced by a fistula between the superior mesenteric artery and the vein]. AB - Presented herein is a clinical case report concerning surgical management of a rare-localization arteriovenous fistula, i.e., between the superior mesenteric artery and vein (the system of the portal vein) complicated by portal hypertension and ascites in a 67-year-old male patient. The check examination performed one month after the operation revealed no signs of either portal hypertension or ascites. PMID- 21032883 TI - [Acute thrombosis of lower-limb arteries: contemporary approaches to therapeutic decision making]. AB - Analysed herein are therapeutic outcomes in a total of 499 patients presenting with acute thrombosis of the aorta and lower-limb arteries and having previously no reconstructive operations on limb arteries on the affected side. Group I was composed of the patients who had during the first 24 hours of hospitalization undergone an emergency operation (n = 146), and Group II comprised those subjected to medical treatment only (n = 353). In Group I, the number of the patients who survived with a preserved extremity amounted to 91.5% of those presenting with grade I ischaemia, equalling 76.5% of those diagnosed with grade IIA, 48.5% of those having grade IIB, and 12.5% for those with grade IIIA. Using conservative measures alone, we had managed to attain complete regression of acute ischaemia in as few as 38% of patients found to have grade I ischaemia and in only 1.5% of grade II patients, with the remaining subjects found to either continue suffering from ischaemic impairments or even have them progressed, which later on required performing a reconstructive operation or primary amputation. The outcomes of surgery in patients operated on later than the first 24 hours after admission to hospital were also much worse: the number of amputations was two times higher as compared with that in Group I. The statistical analysis showed a significant dependence of the acute ischaemia pattern on localization and dissemination of the occlusive lesion. Hence, an emergency reconstructive operation appears to be treatment of choice for acute thromboses of lower limb arteries. An exception may only be made for patients presenting with grade I acute ischaemia, running high operative risk, and having a favourable prognosis of the acute ischaemia course, based on the data concerning localization of the occlusive lesion. PMID- 21032884 TI - [Comparative studies of carotid endarterectomy and carotid stenting in patients with carotid artery stenosis (part II)]. PMID- 21032885 TI - [History of science and research of morphine]. PMID- 21032886 TI - [Effort for renovation of pharmacy education]. PMID- 21032887 TI - [Ancient history of Indian pharmacy]. AB - The study of the ancient history of Indian medicine has recently been revived due to the publication of polyglot translations. However, little is known of ancient Indian pharmacy. Archaeological evidence suggests the Indus people lived a settled life approximately in 2500 B.C. Their cities were enjoying the cleanest and most hygienic daily life with elaborate civic sanitation systems. The whole conception shows a remarkable concern for health. Then, the early Aryans invaded India about 1500 B.C. and the Vedic age started. The Rgveda texts contain the hymns for Soma and those for herbs. The term Ayurveda (i.e., science of life) is found in some old versions of both Ramayana and Mahabharata and in the Atharvaveda. Susruta had the credit of making a breakthrough in the field of surgery. The Ayurveda, a work on internal medicine, gives the following transmission of sages: Brahma-->Daksa-->Prajapati-->Asivinau-->Indra-->Caraka. On the other hand, the Susruta-samhita, which deals mainly with surgical medicine, explains it as follows; Indra-->Dhanvantari-->Susruta Both Caraka and Susruta were medical doctors as well as pharmacists, so they studied more than 1000 herbs thoroughly. The Ayurveda had been used by his devotees for medical purposes. It eventually spread over Asia with the advanced evolution of Buddhism. PMID- 21032888 TI - [The transition of amino acids drug development for 50 years in Japan (part 2)- ethical drugs containing amino acids (except alpha-amino acid parenteral fluid)]. AB - There are approximately 1300 kinds of ethical drugs currently approved for use in Japan, excluding high molecular weight drugs and Chinese medicines. Among them, 81 contain alpha-amino acids, though some consist of a-amino acid parenteral fluid and peptide-type drugs, which include ACE inhibitors. Of these, 30 kinds of drugs are made from both natural and non-natural amino acids, and 51 kinds of drugs are prepared from amino acid derivatives. All of these drugs were developed in the last 50 years. Amino acids moieties such as D-phenylglycine and D phydroxyphenylglycine have contributed to enhancing the stability, absorbability, and effectiveness of many drugs, particularly antibiotics, such as certain types of penicillin and cephalosporin. In recent years, radioactive and antiviral agents containing amino acid skeletons have also been developed for use as anti AIDS medications. PMID- 21032889 TI - [Medicinal history and ginsenosides composition of Panax ginseng rhizome, "Rozu"]. AB - Ginseng is prepared from Panax ginseng C.A. Meyer root. The root of wild P. ginseng has long tortuous rhizome called traditionally "Rozu" in Japanese. In the present historical studies on ginseng, it has been proven that ginseng has sometimes been used after removing "Rozu" due to its emetic effects. However, ginseng with "Rozu" is prescribed in almost all the present Kampo formulations used clinically in China and Japan. Possible reasons for this are (1) some formulations including "Rozu" have been used for vomiting resulting from the retention of fluid in the intestine and stomach, "tan-in" in Japanese, and (2) the present cultivated ginseng has shorter "Rozu" than wild ginseng. Furthermore, it is proved that "Rozu", rich in ginsenoside Ro with oleanane-type aglycone, is distinguished from ginseng roots rich in ginsenosides Rb1 and Rg1 with dammarane type aglycone. This is the first report to declare the distribution of ginsenosides in underground parts of wild P. ginseng. Ginsenoside Ro is a minor ginsenoside in ginseng whereas it is the major ginsenoside in P. japonicus rhizome (chikusetsu-ninjin in Japanese). Ginsenoside Ro is characterized by antiinflammatory effects which differ from ginsenosides Rb1 and Rg1 responsible for adaptogenic effects of ginseng. These results suggest that "Rozu" containing both oleanane- and dammarane-type ginsenosides might be a promising raw material distinct from ginseng root or P. japonicus rhizome. PMID- 21032890 TI - [Historical research of cinchona cultivation in Japan (1): first trial cultivation in Japan in the early Meiji period recorded in Nomutenmatsu]. AB - Cinchona is known as a magic bullet for malaria and its cultivation was dominated by Java on a global scale in the 19th century. In 1875, in accordance with a suggestion by Takeaki Enomoto, the Meiji government made a request to the Dutch government that cinchona seedlings be distributed to Japan. In response to that request, in 1876, 42 cinchona seedlings arrived in Yokohama from Java. It was the first time cinchona seedlings were shipped to Japan. After that, cinchona seeds and seedlings were shipped to Japan a total of three times between 1876 and 1883. The seeds shipped in 1878 were raised at the Nishigahara Agricultural Experiment Station and then planted at nine places in both Okinawa and Kagoshima Prefectures in 1882. The planter was Yasusada Tashiro. However, all of the planted seedlings had died by 1884. The first national farming plan of cinchona in Japan ended in failure. These matters were found in documents included in Nomutenmatsu compiled by the Ministry of Agriculture and Commerce of the Meiji government in 1888. PMID- 21032891 TI - [Starting with camphor--the progress of Nippon Fine Chemical]. AB - In 1918, Nippon Fine Chemical Co., Ltd. (NFC) was founded under the name, Nippon Camphor Co., Ltd. for the purpose of unifying the camphor business throughout Japan. The company manufactured purified camphor as a government-monopolized good. Camphor was used as a plasticizer for nitrocellulose, as a moth repellent, as an antimicrobial substance, as a rust inhibitor, and as an active ingredient in medicine. It was also a very important good exported in order to obtain foreign currency. Later on, after World War II and the abolition of the camphor monopoly, the company started manufacturing products related to oils and fats, including higher fatty acids, and expanded its business by developing a new field of chemical industry. In 1971 the company changed its name to Nippon Fine Chemical Co., Ltd., and made a new start as a diversified fine chemicals company. Recently, the fine chemicals division of NFC has concentrated on rather complex molecules, such as active pharmaceutical ingredients, and other chemicals. Since 2000, NFC have started to supply "Presome", precursors of liposome DDS drugs. NFC is strengthening marketing strategies in foreign countries with unique technologies and products. PMID- 21032892 TI - [Social change and Pharmaceutical Affairs Law (PAL)]. AB - Former Japanese pharmaceutical laws, originally based on the Pharmaceutical Marketing and Handling Regulations enacted in 1874 were in operation for many years before World War II. However, in order to address several drug issues, such as poor drug quality and insufficiences regarding the role of pharmacists during the War, the laws needed to be unified and revised. In this paper, we analyzed the record of discussions held by the Imperial Diet on the bill for the Pharmaceutical Affairs Law (PAL) in 1943. This is also regarded as the origin of the current PAL (LawNo.145 in 1960). Through this analysis, we tried to clarify the relationship between the social change and the role of PAL in society. During the War, the bill was discussed, aiming at the improvement of both human resources who treated drugs, and the quality of drug materials. Diet members discussed three main points, namely, "the duty of pharmacists", "the mission of the Japan Pharmaceutical Association" and "the quality control of pharmaceutical products". Notably, the bill pharmacists are required not only to dispense drugs, a role they had previously, but also to manage drug and food hygiene through the quality control of pharmaceutical products and the inspection of food and drink, in order to improve the public health in Japan. Originally, the law was passed to deal with the extraordinary circumstances during the War, but through our analysis, we found that they proactively improved the role of the law to comply with various drug issues raised during the War, the rapid change of the pharmaceutical hygiene concept and the social transformation. PMID- 21032893 TI - [Drugs in Kamigata Rakugo (a traditional style of Japanese story-telling in Osaka)]. AB - Rakugo, traditional Japanese story-telling, has a history of over 300 years. The stories consist of jokes, anecdotes, and funny messages. The content often includes critical points of view from the perspective of normal people. Some of the targets of criticism are physicians and druggists. This study looked at the number of medical and medicinal items mentioned in kamigata rakugo (rakugo in Osaka). There were ten occasions in which medical/medicinal items were used for practical purposes in scenarios and 27 occasions in which they were simply mentioned. Some of the uses show us the medical and pharmaceutical situation in the 18-19th century in a humorous way. For example, mentions of kyu:moxibustion, biwayoutou:loquat herb tea, and ninjin:ginseng. PMID- 21032894 TI - [Modern technologies for engineering of bioartificial liver implants]. AB - The liver transplantation is the most effective method for treating severe liver disease. The hepatocytes transplantation may serve as the perspective means for treating liver failure. This review analyzes the experimental approaches and perspectives on the adult hepatocytes use for the creation of implanting bioartificial liver module for hepatic failure treatment. PMID- 21032895 TI - [Stress and the thyroid gland]. AB - The review highlights the effects of acute and chronic stress on thyroid metabolism. Special attention is paid to the influence of stress and the direct effects of glucocorticoids on the thyroid status, the activities of thyrocyte iodine uptake, oxidation and organification as well as peripheral metabolism of thyroid hormones (deposition and transport of thyroid hormones, deiodinase activities in different tissues). The role of stress in the development of thyroid pathology is analysed and characteristic features of thyroid function alterations during impaired functioning of the pitiutary-adrenal system are established. The mechanisms of the stress-induced impairments in thyroid functions are of interest for further research, taking into consideration serious consequences of thyroid deficiency for the body, even in subclinical thyroid insufficiency. PMID- 21032896 TI - [Alkylglycerolipids--modulators of tumor cells death]. AB - The review is summarizes current information on biological activity and search of the antineoplastic mechanism of action of alkyl glycerolipids. Special attention is paid to following problems: selective ability phosphorus alkyl glycerolipids, antineoplastic activity, cytostatic and cytotoxic effects of edelfosine and its analogues. The review contains set of the data known for today from the literature, on the possible mechanism cytoyoxic actions of such connections. PMID- 21032897 TI - ["Structure-anti-arrhythmic activity" relationship of N-phenilacetamide derivatives and amides of aromatic carbonic acids]. AB - Using the computer system SARD-21 (Structure Activity Relationship & Design) structural features of high- and low-effective anti-arrhythmic agents have been recognized and the influence of these features on the anti-arrhythmic properties has been evaluated. This information has been used for generation of the model for prediction of anti-arrhythmic effectiveness of pharmaceutical preparations with the 82%-level of recognition by two methods. The recognized structural parameters may be successfully used for design of new highly effective anti arrhythmic drugs, and also for modification of structures of known anti arrhythmic drugs for the increase of effectiveness of their anti-arrhythmic action. PMID- 21032898 TI - [Expression of nuclear hormone receptors PPAR, LXR and RXR in the liver and lipid and glucose levels in blood in susceptible and resistant to hepatocarcinogenesis mice strains]. AB - Earlier it was shown that male mice of the DD/He strain were highly susceptible to ortho-aminoasotoluene (OAT) induced hepatocarcinogenesis, and resistant to spontaneous liver tumor development as compared to the CC57BR/Mv strain. In the present work we have made a comparative investigation of peroxisome proliferator activated receptor (PPAR), liver X-receptor (LXR) and retinoic X-receptor (RXR) mRNA levels in liver as well as concentrations of corticosterone, glucose, lipids and insulin in blood of male DD/He and CC57BR/Mv mice. Using the multiplex RT-PCR method it was found that PPAR-alpha, PPAR-gamma, RXR-alpha and RXR-beta mRNA content was essentially decreased in the liver of DD mice as compared to mice of the CC57BR strain. No significant interstrain differences of LXR-alpha and LXR beta mRNA content were found. In DD micetere was more then the 3-fold decrease of blood content of corticosterone, which is involved in PPAR and RXR regulation. DD mice demonstrated a significant decrease in blood serum glucose and insulin concentrations as well as higher reactivity to insulin as compared with CC57BR mice. Elevated blood total cholesterol and cholesterol HDL level were found in DD mice whereas triglyceride content was basically the same in both mouse strains. It is known that glucocorticoids, PPAR and RXR play crucial role in transcription regulation of inflammation response. Therefore our data allow to suggest that decreased corticosterone level in blood, PPAR and RXR mRNA content in liver of the DD strain may lead to induction of inflammation by OAT exposure, resulting in a high incidence of tumorigenesis in this strain. PMID- 21032899 TI - [Effect of citrate on oxidative status of rats tissues in experimental toxic hepatitis]. AB - The effect of citrate free-radical oxidation intensity and aconitate hydratase, superoxide dismutase and catalase activities in liver and blood serum of rats with experimental toxic hepatitis has been investigated. Citrate administration to rats with hepatitis decreased biochemiluminescence parameters and conjugated diene content in rats tissues, increased under conditions of CCl4-induced liver damage. At the same time aconitase activity, decreased at the pathology, increases. The superoxide dismutase and catalase activities increased in at experimental toxic hepatitis, tended towards control values after citrate administration. PMID- 21032901 TI - [Effect of various modes of surgical injury of the rat buccal mucosa on levels of basic fibroblast growth factor and interleukins 1beta and 6 in the dynamics of regenerative processes]. AB - The content of basic fibroblast growth factor (bFGF) and also interleukins 1beta and 6 (IL-1beta and IL-6) has been investigated in rat buccal mucosa after its surgical injury by an erbium laser (Er:YAG laser) and a scalpel. The laser emission caused a sharp increase in the content of these regulators on the second day after treatment followed by decrease observed on the seventh day. These results may reflect synergistic effect of these peptide regulators in the wound defect. Changes in time-course of bFGF, IL-1beta and IL-6 release in the wound formed by the laser beam compared with the wound induced by the cutting instrument may promote earlier appearance of the proliferation phase. PMID- 21032900 TI - [Effects of catalase activators and inhibitors on ethanol pharmacokinetic characteristics and ethanol and aldehyde-metabolizing enzyme activities in the rat liver and brain]. AB - The effects of catalase regulators (aminotriazole, lead acetate, taurine, di-2 ethylhexylphthalate) on the preference for ethanol, its pharmacokinetics, and activities of rat liver and brain ethanol and acetaldehyde-metabolizing enzymes were studied. Lead acetate (100 mg/kg, i.p., 7 days), aminotriazole (1 g/kg, i.p., 7 days), and taurine (650 mg/kg, i.g., 14 days) decreased ethanol consumption under conditions of free choice (10% ethanol water), whereas di-2 ethylhexylphthalate (300 mg/kg, i.g., 7 days) did not exert any effect on this parameter. Taurine, lead acetate and di-2-ethylhexylphthalate significantly activated liver ADH, MEOS and catalase peroxidase activity. Aminotriazole also activated ADH and MEOS, but inhibited liver catalase. The activities of liver and brain A1DH as well as catalase were insignificantly changed by this treatment. The 7-day administration of lead acetate, di-2-ethylhexylphthalate and aminotriazole administrations significantly influenced the ethanol (2 g/kg., i.p.) pharmacokinetic parameters: the area under the pharmacokinetic curve and the elimination half-life time were significantly reduced, whereas the elimination constant and clearance were increased. This unequivocally indicates accelerated ethanol elimination. The 14-day ingestion of taurine insignificantly changed the parameters of ethanol pharmacokinetics in rats. PMID- 21032902 TI - [RNA tumor marker levels in blood of patients with malignant tumors of the gastrointestinal tract]. AB - In order to develop a diagnostic panel, mRNA levels of tumor marker genes have been evaluated in capillary blood of patients with various malignant tumors of the gastrointestinal tract (GIT) by means of the method of reverse transcription combined with real-time PCR with detection of reaction products using TaqMan probes. Use of small volumes of capillary blood did not decrease sensitivity of this method. RNA expression of telomerase (mhTERT), alpha-fetoprotein (mAFP), carcinoembryonic antigen (mCEA) and cytokeratin-20 (mCK-20) was higher in most patients with tumors. Blood of donors or non-oncological patients contained much lower (trace) amounts of the RNA markers. The RNA markers are characterized by reasonably high specificity and sensitivity acceptable for diagnostic application. The mhTERT marker was the most universal one and exhibited the highest specificity and sensitivity. Combined determination of several RNA markers increased sensitivity of this method. It is concluded that determination of RNA markers in small volumes of capillary blood may be used for screening, primary diagnostics, and postoperative monitoring. PMID- 21032903 TI - [Share of extracellular mutated mitochondrial DNA increases in plasma of lung cancer patients following radiotherapy]. AB - Quantitative and qualitative changes in circulating extracellular DNA (ec-DNA) of blood plasma are considered as markers for diagnosis and prognostic of tumor pathology. We investigated the content of mutant copies of the circulating extracellular mitochondrial DNA (ec-mtDNA) in blood plasma (using the enzymatic method, based on the cleavage of DNA with unpaired bases by CEL-I endonuclease) in 8 patients with lung cancer before and after radiotherapy, as well as in healthy young and elderly donors. It was found that in the plasma of healthy elderly donors share of ec-mtDNA with mutations (consisting of total circulating DNA) is much greater, than that of young donors. On the other hand, in the plasma of lung cancer patients (aged 70-76 years) before radiotherapy a substantial increase in the share of ec-mtDNA with mutations, compared with that of healthy elderly donors. Following radiotherapy, patients with lung cancer found a twofold increase of the proportion of ec-mtDNA with mutations in the total circulating plasma DNA. This increase is largely, perhaps due to the release of ec-mtDNA with mutations from dying tumor cells and cells damaged by normal tissues. PMID- 21032904 TI - [The impact of controllable factors on mortality due to diseases of digestive system in Tverskaya oblast]. AB - The article deals with the assessment of the impact of various social, biological and medical factors on the level of mortality of diseases of digestive organs in hospitals of certain districts of Tverskaya oblast. The controllable factors are determined impacting on the level of mortality of digestive system pathology and depending mainly of organization and quality of medical care at various stages of patient monitoring. The expertise technique was applied to evaluate the tactics of carried out treatment and the causes of diagnostics errors entailing preventable death and possibility of preventing lethal outcome. The study results can be used by health administrations and medical institutions to develop target programs reducing the preventable mortality of population. Another direction ? to impact specific causes of death in various subjects of the Russian Federation considering territorial characteristics of local health services and resource support of health care system in particular region. PMID- 21032905 TI - [The economic culture of medical institution as the factor of innovative development]. AB - The article presents the results of study of economic culture of sanatorium type medical institution based on the analysis of its components sorted out with specially developed procedures. The medical organizational pattern of enhancing the economic culture of sanatorium type medical institution was proposed. It's effectiveness was checked in the medical organizational experiment. PMID- 21032906 TI - [The attitude of health workers to the new pay system for labor]. AB - The paper provides the results of the sociological survey to ascertain the opinions of physicians and paramedical personnel on the introduction of the new pay system for labor in a federal budget institution. The findings indicate that health personnel positively responded to the introduction of the new pay system for labor, their personal interest in achieving the quality indicators of their work has increased. PMID- 21032907 TI - [The characteristics of the organization of emergency medical care in the Republic of Dagestan]. AB - The analysis is presented relating the organization of emergency medical care in the Republic of Dagestan. The analysis of official statistic data revealed that from 2005 and until the present time there is a sustained increase of resourcing to this form of service by the population both in the republic in general and in urban areas. The increase of appealability among urban population is significantly higher than in the republic. This characteristic trait can be explained by the fact that the rural areas of the Republic continue to significantly log behind in the provision with main types of medical services. According the official statistic data, in 2005 the difference in appealability between urban and rural areas consisted 133, in 2006 ? 128, in 2007 ? 115, in 2008 ? 102 per 1000 of population. In the structure of emergency calls from rural and urban population the cases of sudden diseases. The portion of emergency calls by chronic patients has a clear tendency to decrease both among rural and urban population. The mentioned trends need the adjustment of organization of emergency medical care in rural areas, including intensive development of material technical and manpower of rural substations of emergency medical care. It is timely to consider the issue of development in the Republic of Dagestan the twenty-four-hour integrated consultative control board of emergency medical care to advice by phone the medical emergency teams, the personnel of district hospitals and feldsher obsteritian stations and general practitioners. PMID- 21032908 TI - [The characteristics of anaesthesiologic service in territories with low density of population settlement]. AB - The data of the study of sociological and expertise survey of physicians of surgery profile and anaesthesiologists-reanimators is presented. The Delphi technique was applied to determine the qualitative degree of interrelationship of elements? Characteristics in the functioning of the anaesthesiologic service. These studies are topical because of serious issues of anaesthesiologic service in the territories with lower density of population settlement to be resolved through the enhancement of its overall functioning. PMID- 21032909 TI - [The most frequently quoted national journals in the thesis studies of sociology of medicine]. AB - The analysis of the most frequently quoted national journals in dissertation studies in the field of sociology of medicine established that the most demanded among periodicals of public health and health care are "The problems of social hygiene, health care and history of medicine", "The health care of the Russian Federation" and "The health care". This is a testimony of recognition of significance of publications in these periodicals made by researchers defending dissertations. PMID- 21032910 TI - [The organization of integrated care to children with epilepsy]. AB - In the Stavropol Kray four-stage system of caring patients with epilepsy is developed. It is consisted of local physician-district neurologist-epileptologist of consultative polyclinic of kray pediatric hospital-psycho-neurologic department of kray pediatric hospital. The implementation of treatment standards permitted to ultimately approximate the actual care to the patient with epilepsy. PMID- 21032911 TI - [The legal regulation of medical care in high-technology centers]. AB - The article deals with the issues established during analysis of normative legal base regulating the activities in provision of high-technology medical care. The following positions are considered: the generation of public task to provide high technology medical care, licensing and standardization; the issues of patients? Rights safeguard; the approaches to determine the types of high-technology medical services; the issues related to rendering paid services; the enhancement of organizational legal form of institutions rendering high-technology medical care. The recommendations on the development of the legislation in force are made. PMID- 21032912 TI - [The sociological survey in the organization of evaluation of quality of medical care in the system of mandatory medical insurance]. AB - The three-year experience of medical insurance company "ASKO-VAZ" of implementing the technique of sociologic surveys is discussed. The purpose was to study the degree of citizens? satisfaction of their interaction with medical sub-system in receiving medical care. The issue of awareness of medical personnel about functioning of system of mandatory medical insurance was examined. PMID- 21032913 TI - [The experience of public guarantees of free-of-charge medical care foreign countries]. AB - The article deals with the analysis of the volumes of financing of public guarantees program of free-of-charge medical care and its algorithm of its elaboration in foreign countries. In the advanced countries, the higher financing of public health permit to ensure factually overall population the full free-of charge spectrum of up-to-date medical interventions as a "public guarantees pack". It includes the pharmaceuticals supply in outpatient conditions and in most cases the long-term care services. In economically advanced countries, the general trend is the transfer from fundamental principles ("everything needed") to the more transparent approaches in case of implementation of the guarantees to achieve the balance between actual financial resources and stated population guarantees. PMID- 21032914 TI - [The interdisciplinary approach to the history of psychiatry]. AB - The historical approach is applied ever often to investigate various problems of medicine. The specificity of methodological approach to the history of psychiatry is related with the necessity to implement the historic methods of study not only medicine but other disciplines (non-medical ones included) and the needs of society the progress of medicine depended. The study of problem in this context demands the implementation of the interdisciplinary system to provide the complimentary methodological approach to more comprehensive understanding of historical patterns of development of science and its perspectives. A good example of such a system is synergetics which provide the possibility to evaluate different characteristics and patterns of non-linear historical process. The main target of this approach is to reveal the unobvious patterns, to determine the interdependent algorithms and tendencies escaping from the attention of disciplinary-specific approach to the history of medicine. PMID- 21032916 TI - [The fiftieth anniversary of the Russian Peoples Friendship University (on the history the faculty of medicine)]. AB - The article presents the history of the Russian Peoples Friendship University and of the faculty of medicine in particular from the moment of its organization to nowadays. PMID- 21032915 TI - [The Arkhangelsk society of physicians--one of the first public medical organizations in Russia]. AB - The Arkhangelsk society of physicians was officially opened in 1863. The purposes and tasks of the organization were the following: to one another with mutual education, information about important cases and news; to follow the development of medical sciences by means of journals and books subscription; to study sanitary hygienic conditions in Arkhangelskaya gubernia. The society supported in Arkhangelsk the organization of the feldsher midwife and veterinary schools (1876); the organization of the congress of physicians of Arkhangelskaya guberina (1907); the organization of spearheads to lecture the population (1911); the organization of public group "The drop of milk" $ participated in the Red Cross actions "White flower" and "Yellow flower". The activities of society played an important role in the consolidation of physicians of Arkhangelskaya guberina, promoted the enhancement of their professional qualification and the development of health care in Russian North. PMID- 21032917 TI - [The physician exhibits fantasy, in addition to cleansing the drug of madness]. AB - The Musee Rolin of Autun, Burgundy (France) owns an interesting and rather large picture, entitled Le medecin guarissant phantassie, purgeant aussi par drogues la folie; it was originally painted on wood and was used as a shop-sign at the Cosseret Pharmacy, at 20 Grand Rue Chauchien, Autun, from the beginning of the XVIIth century to 1897. A naive description, the same that might have been by the clients, gives more fright than trust in the treatments on display. In the background, before rows of bottles, a medical action that looks like a purge is in progress. In the foreground a torture scene must be interpreted. The juxtaposition and alteration of traditional medical elements tend to spread confusion in the spectator's mind and introduce him into a world where reality is disturbed. This communication aims at showing that this picture about evacuation of madness has a medical meaning, showing that this icon of the evaciation of madness refers to medical theories, from Galen to Vesalius, and is a satirical representation of quacks'practices. PMID- 21032918 TI - [150 years after Darwin]. AB - Are Darwin's evolutionistic theories everlasting? According to the author who points out Darwin's family circle and the chronology of his times the data of modern knowledge--cyto biology, genome, virology--don't seem to coincide with the evolution theory and the coming of the living beings. PMID- 21032919 TI - [Joseph-Francois Bourdier from La Mouliere and his work in the five-year fever]. AB - J.-F. Bourdier was one of the doctors of the Faculty of Paris. As a medical doctor for the Archduchess Marie-Louise, he was also able to conduct his scientific research. In 1808, during the difficult time of the Continental System, J.-F. N. took part in the research work on a substitute for cinchona and tested some treatments. However, being not a chemist, he could not make any chemical analysis. Then, the chemists Caventou and Pelletier discovered quinine in 1820. PMID- 21032921 TI - [Rob of the physician. An unequaled example of the past "secret remedy"against syphilis]. AB - Since the 16th century syphilis treatment increased the use of mercury despite its strong toxicity. In 1764 in Paris Doctor Boyveau created the so-called rob without mercury and experimented it at the Bicetre Hospital with the approval of the medical authorities. It was a real important success lasting till 1828, as Giradeau de Saint-Gervais took back the brand. However the suspicion of mercury in the remedy could not be proved. PMID- 21032920 TI - [Ambroise Pare, landlord]. AB - Pare is well-known through many papers. His incomes allowed him to have a middle class Parisian living. It is impossible to have an accurate knowledge of his fortune before his death but we have a good idea of his landed property. In fact as a Parishioner of Saint-Andre-des-Arts Church he probably was a landlord only in Paris and its vicinity with a building (rue de l'Hirondelle), two houses (rue Garanciere), Meudon, Cormeille-en-Parisis and La-Ville-Du-Bois which the authors describe the present state of. PMID- 21032922 TI - [The pharmacopoeia for the poor of Professor Nicolas Jadelot from Nancy in 1784 1785]. AB - In 1785, Doctor Nicolas Jadelot, a professor at the Faculty of medicine of Nancy, published a little book entitled Pharmacopee des pauvres. Four parts composed it: pharmaceutical formulas from Saint-Charles Hospital, some corrections, a table of materials and a table of the use of drugs. In octavo, the book gathered 212 pages and 342 formulas of drugs, most of the materials beeing found in plants. The book was devoted to hospitals, houses of charity and all persons working for poor people. However, the examination of the pharmaceutical formulas shows that physicans and apothecaries have certainly been its best users, mainly the members of the Royal College of medicine and the six apothecaries of the town, associated with these physicians in a charitable medical activity directed towards this poor people. PMID- 21032923 TI - [Joys and sorrows of three surgeons from Limoge from the French revolution in the Second Empire]. AB - Leonard Cruveilhier (1760-1836), Bruno Giraud (1768-1811), Leonard Boudrye (1769 1852). The author deals with their biographies during a period marked by wars. Descended from middle-class and students in Paris they were promoted through campaigns and battles. After the First Empire Boudrye and Cruveilhier took back their medical work in Tulle and Limoges while Giraud was selected by King of Holland, Louis Bonaparte, but unexpectedly died in 1811. Their medical careers were glorious but they were submitted to the consequences of the political changes. PMID- 21032924 TI - [The pharmacist Ludovic Dardenne and his chocolate hundred-years-old]. AB - Launched in 1910, the brand "Yo-Yo" made the fame of the chocolate factory of the pharmacist Ludovic Dardenne for Luchon. It was then replaced by a "chocolate of regime" still marketed nowadays. The authors present three elements susceptible to inform this transformation: the first presentation of the chocolate Yo-Yo, its patent of manufacturing such as it was registred in 1911, and two typographic patches praising the merits of the chocolate of regime in the 60's. PMID- 21032925 TI - [History of sun protection]. AB - Human behavior towards the sun has changed over the years along with trends. Tan succeeded the white complexion. The sunscreens appeared recently in history. It is lining up with the discovery of bad effects due to prolonged exposure to ultraviolet at the end of the 19th century. Initially, those products had no signs of efficacy on their packaging, then the solar protection factors increased gradually, up to a limit value of 50+ more recently. PMID- 21032926 TI - [Yvonne Marie Rosengart-Famel, her life and pharmaceutical career]. AB - Yvonne Marie Rosengart-Famel (1912-?) is the granddaugther of Pierre Famel, the founder of the Pharmacy and the Laboratoires Famel. After passing her A-Levels in 1929, she trained in pharmacology partly in her grandfather's pharmacy, and partly in the Pharmacy Lefevre. She was a student at the Faculty of Pharmacy in Paris, where she presented a doctoral thesis on the botanical, chemical and pharmacodynamic studies of several species from the genus Anabasis and Haloxylon. After the death of Pierre Famel she managed the Society of Laboratoires Famel from 1942 to 1963. We lose her trace from this date, when she was in the United States. PMID- 21032927 TI - [Comparison of French and American formularies in 1945: multiple discrepancies that come from technical, political and social differences]. AB - At the end of the Second World War, L'Officine from Dorvault, 1945 edition, gives the state of the art situation of drugs in France. At the same date, is published New and Non-Official Remedies in Chicago, IL, USA. Tiffeneau in France publishes an other reference book of Pharmacology in 1947 (6th edition). From the comparison of these books appears a mismatch between the French and US remedies at the end of the war: well developed within USA, antibiotics, anti-allergic drugs and contraceptive products are more or less absent in France. Analysis of the differences appears related to technical and economical reasons but also to politic and social ones. PMID- 21032928 TI - [Family, professional, "meusian" and Parisian relationships between the pharmacists J. Bataille, J.-N. Trusson, N. D. Moutillard and T. Huraut]. AB - Jean-Nicolas Trusson is well known in the history of Parisian pharmacy. Born in 1744 in Euville, in the vicinity of Commercy, in Lorraine, he was in near relations by his mother with Joseph Bataille, also well known and whose half length portrait is exhibited in the "Salle des Actes" of the Faculty of Pharmacy in Paris. It seems that the extraction of Bataille is unknown. Our work indicates that he was born in october 1816 in Pagny-sur-Meuse, some kilometres from Euville towards Toul. Trusson was the successor of Bataille and he remained in his pharmacy until 1809 where his own successor was Nicolas Denis Moutillard. Moutillard's father was Joseph Moutillard, an apothecary of Commercy, whose mother was Jeanne Trusson, who was the first cousin of Jean-Nicolas Trusson's father. Then, Theodore Huraut, Moutillard's successor in Paris, was also born in Commercy, in year 1813. He studied pharmacy in Bar-le-Duc, then in Paris with Moutillard and at the school of pharmacy. Taking his place between 1840 and 1844, he became a member of the "Societe d'emulation pour les sciences pharmaceutiques" and of the "Societe de pharmacie de Paris". Beeing the author of more than twenty papers devoted to practical community pharmacy, Huraut died in Paris in 1855. PMID- 21032929 TI - [The birth of the modern Moroccan pharmaceutical legislation]. AB - Currently the Moroccan pharmaceutical profession is about to celebrate its centenary. Since the French protectorate period a great evolution occurred; from little herbalist shops in the countryside the dispensaries became real small companies managed by doctors in pharmacy. The objective of this study is to clarify the first pharmaceutical legislative texts in Morocco and the context of their adoption. It also aims at pointing out, describing and analyzing the provisions' evolution that governed the general pharmacy practice conditions during protectorate. Based on the information available we examined and studied successively these practice conditions and more particularly the diploma, the age and the officinal training course. PMID- 21032930 TI - [The entrance of women to medicine]. AB - From their first registration at the Faculty of Medicine of Paris to the opening of a clinic, the first women doctors met as much opposition as support. Between 1866 and World War I, medical female students and the female physicians are present in the press and public debates. They are few in number, rarely French. Through their history and their writings, this article seeks to understand the concept of"female nature" and how our French female doctors offer a new concept of medicine and its practice. PMID- 21032931 TI - [The teaching of history of medicine in Paris in the 19th century (1794-1914)]. AB - The defeat of the erudition which characterised the teaching of history of medicine at the end of the 19th Century, was a sign of the passing of one culture to another. This article examines two aspects of Parisian teaching, the institutional and the educational. In addition the question of the usefulness of this teaching is examined, both in relation to Paris and also to the whole field of French medicine. PMID- 21032932 TI - [Ambroise Pare and Latin]. AB - We report a study of a medical book written by Antoine Mizaud (Memorabilium utilium, in ac iucundorum aphorismos Arcanorum omnis generis locupletes, perpulchre digestae), which was written in Latin, but has been extensively annotated in French.The book is from the personal collection of one of the physicians of Napoleon III. There is an oral tradition within his family that one of the works in the book had been annotated by Ambroise Pare. We know very little, apart from a few receipts and his signature, about the writing of the master of French surgery. Did he understand the language of Galen? There are many annotated passages in the works of Pare which are in the book. We examine whether these annotations were actually made by Ambroise Pare or whether they were done for him. PMID- 21032933 TI - Selective strategy for thrombus management in STEMI interventions. PMID- 21032934 TI - Summary of the International Federation of Dental Hygienists house of delegates workshop. AB - OBJECTIVES: The 2007 International Federation of Dental Hygienists (IFDH) House of Delegates participated in a two day forum to discuss professional topics of interest and to provide a focus for the direction of the profession and the IFDH. MATERIALS AND METHODS: Delegates were asked to select a work group of interest based on four main topics: promoting evidence-based dental hygiene practice, procedures, and products; disease prevention and health promotion for primary health care; promoting interprofessional collaboration; and, reframing dental hygiene education. Each work group was challenged to address key questions and create a summary statement with recommendations to the IFDH. RESULTS: Each work group identified numerous areas for professional growth and development and created a list of aspirations for the profession and the association to achieve. CONCLUSION: The IFDH has made a commitment to the HOD to incorporate proposed recommendations and future aspirations. PMID- 21032935 TI - New evidence on bacteraemia. PMID- 21032936 TI - Is your knowledge up-to-date? PMID- 21032937 TI - A review of maggot debridement therapy to treat chronic wounds. AB - This literature review aims to clarify whether using maggot debridement therapy (MDT) for the removal of devitalized and infected tissue in chronic wounds is a valuable tool for healing. To undertake a literature review, the British Nursing Index, Ovid-Medline and the CINAHL databases were searched from January 1960 to June 2010 using the following terms: maggot debridement therapy, chronic wounds, granulation, infection, and cost-effective. The evidence suggests that MDT is more effective than other methods of debridement for wound bed preparation, although it has not been proven to eliminate problems associated with recurrent infections. This therapy has also not been proven to accelerate the healing process; however, more research needs to be undertaken into this and the cost effectiveness of treatment. PMID- 21032938 TI - Prophets, saints, and matriarchs: portraits of old women in early modern Italy. AB - This essay examines portraits of old women that were produced for the households of the professional and elite classes in Emilia-Romagna, Lombardy, and the Veneto during the second half of the sixteenth century, when, as a result of religious and social reform, women's lives came under increasing scrutiny. By interpreting the portraits within the context of prescriptive texts on the stages of women's lives, this study argues that the portraits provide evidence for the pivotal role of old women within the moral and symbolic order of the family, as well as in the wider community beyond the home. PMID- 21032939 TI - [Four decades of historiography on evolutionism in Spain]. AB - Historiographical production on evolutionism in Spain has given rise to a set of very appreciable original works both in number and quality. Indeed, the diffusion of evolutionist theories offers very attractive materials of study, as much from the point of view of the history of the ideas and the scientific theories, as from the approach around the studies of the broad social interaction that science establishes with its environment. The deep ideological and religious implications that the evolutionist question involves find in the Spanish case an especially interesting example. This paper tries to offer an overview about some proposals presented in the last forty years, so that it can give a cause for reflection for new research lines in the future. PMID- 21032940 TI - [Sciences and races in Brazil ca. 1900]. AB - This paper attempts to provide a general overview about the way in which Brazilian medicine and physical anthropology gave a naturalistic approach to the idea of race and to the "problem" posed by the mixture of races in the country during the second half of the 19th century and the beginning of the 20th century, coinciding with the introduction of evolutionism in Brazil. PMID- 21032941 TI - [Debating Darwin in Spain: anti-Darwinian evolutionary theories and modern synthesis]. AB - Centenary celebrations of Darwin's birth were held in Valencia and Lorca in 1909. Fifty years later, the meetings and the publications of the Spanish scientific community on the occasion of the centenary of the publication of "On the Origin of Species" showed a proximity and an acceptance towards the theses of the evolutionary modern synthesis. During the first half of the 20th century, there were controversies in Spain between the Darwinian and anti-Darwinian positions. In addition, non-Darwinian evolutionary theories were spread and supported. Though the assumptions of the synthetic theory of evolution were soon known, commented and discussed, the majority trend in the 40s and 50s was to incline towards finalist and vitalist interpretations of evolution. PMID- 21032942 TI - [Lamarck and the adaptive conservation of life]. AB - This paper studies Lamarck's evolutionary thought through four analytic elements. Firstly, Lamarckian construction of a founding evolutionary archetype. Secondly, the interpretation of nature as a material system where the organic change represents a continuous process aimed at the adaptative conservation of life. Thirdly, the definition of a genealogical process on the origin of species which identifies the natural method. Fourthly, the redefinition of the concept of species applying the arguments of temporary relativity and individual instability. PMID- 21032943 TI - [In search of biology. Reflections on evolution]. AB - After 150 years conceiving and dealing with Nature in terms of competence, costs benefits, exploitation of resources, strategies..., we have managed to make it enter into a "recession." This estrangement from reality and from natural phenomena, has seriously jeopardized the future of mankind on our planet and makes it necessary, even urgent, the search for a conception of biology based on scientific concepts and vocabulary that re-connects us with Nature before it is too late. PMID- 21032944 TI - [Darwinism and the meaning of "meaning"]. AB - The problem of the meaning of life is herewith contemplated from a Darwinian perspective. It is argued how factors such as existential depression, the concern about the meaning of "meaning," the problem of evil, death as the end of our personal identity, happiness as an unachievable goal, etc. may well have an adaptive dimension "controlled" neither by ourselves nor obscure third parties (conspiracy theories) but "simply" by our genes (replicators in general) so that little if anything is to be done to find a radical remedy for the human condition. PMID- 21032945 TI - [Lamarck needs Darwin: the search for purpose in the study of evolution and of history]. AB - Lamarck's theory of the inheritance of acquired characteristics and immediate responses to environmental challenges has offered a promise of protagonism of human beings and their fellow travellers, the other organisms, in the evolutionary process. Darwin's theory about evolution by natural selection does not offer this consolation and does not presuppose anything else other than gradual changes in the composition of natural populations. The study of ecology, ethology, neurobiology, animal culture, psychology and human history reveals that the lamarckian interpretations of change and character transmission processes always assume what they intend to explain, that is previous processes of darwinian evolution that guarantee the adaptive nature of the observed responses. The permanent search of direction and intentionality in evolutionary processes by many scientists suggests the limited acceptance of materialistic explanations as those offered by Darwin's theory. PMID- 21032946 TI - Incarceration and social inequality. PMID- 21032947 TI - Punishment's place: the local concentration of mass incarceration. PMID- 21032948 TI - The paradox of women's imprisonment. PMID- 21032950 TI - St. Anthony Hospital, Gig Harbor, Washington. PMID- 21032949 TI - [In vitro and in vivo study of chondrogenesis on the hybrid scaffold from fibrin modified PLGA and adipose-derived stem cells]. AB - AIM: To investigated the effect of the presence of fibrin in the PLGA scaffold on the differentiation of adipose-derived stem cell (ASCs) into chondrocytes in the chondrogenic media. METHODS: ASCs were prepared by colagenase I digestion of fat from rabbits. The PLGA scaffolds were prepared by LDM technology. The hybrid scaffold was fabricated by a freeze-drying method. Isolated ASCs were cultured in the PLGA without and with fibrin up to 14 days in specific chondrogenic medium. The surface property of the scaffold was observed by SEM. Cell attachment was evaluated, and glycoaminoglycans (GAGs) content was tested by biochemical method. RESULT: When ASCs were seeded within fibrin modified PLGA scaffold in vitro, enhanced cellular attachment and differentiation were observed compared to unmodified PLGA scaffold. The study from articular cartilage defect repaired showed that the group from the autologous ASCs seeded on fibrin-PLGA scaffold had better chondrocyte morphology, tissue integration, continuous subchondral bone, and much thicker newly formed cartilage layer as compared with other groups. CONCLUSION: Such modification of PLGA may ultimately enhance the efficacy of tissue engineered scaffolds for cartilage tissue engineering using ASCs. PMID- 21032951 TI - Milstein Family Heart Center, New York City. PMID- 21032952 TI - Penn State Hershey Cancer Institute, Hershey, Pennsylvania. PMID- 21032953 TI - KP-1461: a novel anti-HIV drug in limbo? AB - The path of an experimental drug from the laboratory to U.S. Food and Drug Administration (FDA) approval is typically long, rocky, and uncertain. It is especially so for a drug that turns common wisdom on its head. Take KP-1461, a new type of antiretroviral drug from Koronis Pharmaceuticals in Seattle. Unlike all of the currently approved anti-HIV drugs, which aim to reduce the amount of virus in the body by blocking viral replication, KP-1461 was designed not to inhibit replication, but rather to force newly created HIV to become less able to infect human cells. PMID- 21032954 TI - Inflammation, immune activation, and HIV. AB - Inflammation is a broad term for what happens in the body when the immune system is activated to counter a threat. A healthy immune response is key to good health, but ongoing immune activation and inflammation due to a persistent threat such as chronic HIV infection can lead to many different problems throughout the body. PMID- 21032955 TI - Understanding and managing peripheral neuropathy. AB - Peripheral neuropathy is the most common neurological disorder in people with HIV infection. It can be a major source of pain and discomfort and a limiting factor in antiretroviral treatment. Since the introduction of highly active antiretroviral therapy (HAART) in the mid-1990s, the overall incidence of neurological complications of HIV--such as HIV-associated dementia and central nervous system opportunistic infections--has decreased, however, rates of peripheral nervous system complications remain high. PMID- 21032956 TI - Hormonal contraception for HIV positive women. AB - Barrier methods such as condoms and diaphragms are the most commonly used forms of birth control among HIV positive women. Sterilization is the second most popular method and hormonal contraception is the third Hormonal contraceptives, when used correctly and consistently, are highly effective in preventing unintended pregnancy and are also useful for treating health conditions such as painful menstruation. PMID- 21032957 TI - HIV and the recession: staying well in tough times. PMID- 21032958 TI - Positioning your practice for good financial health. PMID- 21032959 TI - Prime time to increase efficiency through operations. PMID- 21032960 TI - Qwning up. Take these steps to protect the value of your practice--and the dividends it pays you. PMID- 21032961 TI - Front and center. Investment in staffing, technology shows patients you care. PMID- 21032962 TI - Strength in numbers. Examining accounting and finances can illuminate ways to save, bring in revenue. PMID- 21032963 TI - How much is your medical practice worth. Arriving at a fair price tag for a medical practice is both a science and an art. Here's what you need to know about how it's done. PMID- 21032964 TI - 10 tips to maximize your time. PMID- 21032966 TI - The curious illness. Every illness can be a learning experience for you and your patients. PMID- 21032965 TI - Lessons from Randy. Subtle clues from your patients can help you head off regret. PMID- 21032968 TI - Developing your competitive edge. Take the time to consider what makes you better. PMID- 21032967 TI - Treat ZPIC audit notice with urgency, seriousness. PMID- 21032969 TI - Nursing Praxis in New Zealand. PMID- 21032970 TI - Children living with a mentally ill parent: the role of public health nurses. AB - Public Health Nurses work with children under 18 years in schools and the community. Increasingly children are living with a parent suffering from a mental illness. Consequently Public Health Nurses are encountering more mental illness as part of their practice. The research reported in this article aimed to identify the Public Health Nurse's role with regard to children in these circumstances. A qualitative research design was used with eight Public Health Nurses working in rural and urban settings. Participants engaged in a focus group from which data were gathered and analysed thematically using axial coding. To evaluate the identified themes six of the participants went on to take part in a further focus group. The three key themes identified were Advocacy, Assessment, and Relational Knowing and Clinical Practice. It emerged that the role of Public Health Nurses working with such families involved advocating for the child, using a range of assessment skills to gather relevant information and make referrals, with all informed by expert knowledge and clinical experience. Findings indicate the need for more acknowledgement of the frequency with which Public Health Nurses are encountering problems associated with mental illness; and hence the need for provision of appropriate education and support that will enable them to effectively advocate for children's safety and wellbeing. PMID- 21032971 TI - Practice nurse use of evidence in clinical practice: a descriptive survey. AB - The role of practice nurses is a specific feature of the modernisation agenda of the New Zealand health service. Increasing importance is being placed on service improvement through effective decision making and enhanced clinical performance. To contribute to the development of primary health care it is crucial that nurses have the skills to appropriately implement research based and other evidence in practice. This study involved 55 West Auckland practice nurses working in the general practice setting. The aim of the study was to describe nurses' perceptions of their use of evidence-based practice, attitudes toward evidence based practice and perceptions of their knowledge/skills associated with evidence based practice. An additional aim was to determine the effect of educational preparation on practice, attitudes and knowledge/skills toward evidence-based practice. A descriptive survey design was selected for this study. The results demonstrated that nurses' attitudes toward evidence-based practice, knowledge and skills relevant to the implementation of evidence-based practice and the educational preparation of the nurses were important factors influencing the effective utilisation and application of research results in practice. Educational interventions are identified as an integral aspect of implementing evidence-based practice and enhancing practice nurses' knowledge and skill relevant to the use of evidence in practice. Further research is needed to assess the contextual factors which can inhibit or promote achievement of evidence-based practice by practice nurses. PMID- 21032972 TI - What do New Zealand pre-dialysis nurses believe to be effective care? AB - In New Zealand, and globally, the incidence of patients developing chronic kidney disease and entering the pre-dialysis phase is increasing at approximately 6% per year. The specialist pre-dialysis nurse plays a key role in providing care to this complex group of chronically ill people, but as yet no literature indicates what constitutes effective pre-dialysis nursing care. This paper reports on qualitative research that asked a group of New Zealand specialist renal nurses what they believed comprised effective pre-dialysis nursing care. Semi-structured phone interviews were undertaken with eleven pre-dialysis nurses from throughout the country. Through inductive analysis a number of key themes were identified. These were; a strong nurse patient relationship, a comprehensive holistic nursing assessment and timely and appropriate patient education. Commonly used measurable indicators, timely initiation of dialysis and formation of dialysis access prior to treatment, were also considered important but essentially seen as out of the nurse's control. We argue that to ensure pre-dialysis care is effective it is important to not only measure quantifiable parameters but also consider the qualitative elements identified as being at the heart of effective pre-dialysis nursing practice. PMID- 21032973 TI - On the etiology and significance of palatal and mandibular tori. PMID- 21032974 TI - A man for the ages. PMID- 21032975 TI - Dr. Spahl comments on Dr. Dennis Brenkert's article in the July 2010 issue of CRANIO. PMID- 21032976 TI - Temporomandibular joint method to study the morphology and relationship of the hard structures. AB - Different methods have been suggested to study mandibular condylar position. These methods are based on the study of the joint space between the condylar head surface and the glenoid fossa. In all of these methods, joint structures were always regarded as healthy and in ideal shape, a fact that we know to be not always true. The mandibular condyle is a structure that may suffer shape alterations, and its use as a reference structure might lead to misinterpretation of the method. For this reason, the goal of this paper is to develop a new method, which enables study of the relationship between the hard structures that constitute the joint by finding references far from the measurement area. This method allows for revelation of an antero-posterior relationship and a rotational behavior through the study of the condylar axis. PMID- 21032977 TI - A reproducibility method to test lip-closing strength in preschool children. AB - This cross-sectional study tested the reproducibility of a simple button-pulling system for measuring lip-closing strength in normal preschool children and compared their strength to that of normal adults. The sample consisted of 348 preschool children and 123 adults. Lip-closing strength was measured by inserting a button, fastened to a piece of string, into the vestibule between the incisors and lips with minimal mouth opening. The string was attached to a digital tension gauge and was pulled parallel to the floor. Maximum tension, with three repetitions, was recorded at the instant that the button was pulled out of the mouth. Multilevel statistical models were used to evaluate any differences in contractive muscle strength between age groups and between the genders. The strength in children increased significantly from three years to five years (p<0.01). Gender-related differences were found in adults but not in preschool children. Inter-individual variation at each age was larger than intra-individual variation. Measurement of lip-closing strength by button pulling is highly reproducible in children and has potential clinical and research applications. PMID- 21032978 TI - Clinical significance of sleep bruxism on several occlusal and functional parameters. AB - The aim of this study was to evaluate the association between various functional and occlusal parameters and sleep bruxism. Thirty-nine (39) sleep bruxism patients and 30 controls participated in this investigation. The assessment of sleep bruxism was performed using the Bruxcore Bruxism-Monitoring Device (BBMD) combined with a new computer-based analyzing method. Sixteen functional and/or occlusal parameters were recorded. With a mean slide of 0.95 mm in the sleep bruxism group and a mean slide of 0.42 mm in the control group (Mann Whitney U test; p<0.003), results solely demonstrated a significant group difference regarding the length of a slide from centric occlusion to maximum intercuspation. The results suggest that the slightly pronounced slide could be of clinical importance in the development of increased wear facets in patients with current sleep bruxism activity. Following further evaluation including polysomnographic recordings, the BBMD combined with this new analyzing technique seems to be a clinically feasible instrument that allows the practitioner to quantify abrasion over a short period. PMID- 21032979 TI - Effects of orofacial myofunctional therapy on temporomandibular disorders. AB - The objectives of the current study were to analyze the effects of orofacial myofunctional therapy (OMT) on the treatment of subjects with associated articular and muscular temporomandibular disorders (TMD). Thirty subjects with associated articular and muscular TMD, according to the Research Diagnostic Criteria (RDC/TMD), were randomly divided into groups: 10 were treated with OMT (T group), 10 with an occlusal splint (OS group), and 10 untreated control group with TMD (SC). Ten subjects without TMD represented the asymptomatic group (AC). All subjects had a clinical examination and were interviewed to determine Helkimo's Indexes (Di and Ai), the frequency and severity of signs and symptoms, and orofacial myofunctional evaluation. During the diagnostic phase, there were significant differences between groups T and AC. There were no significant differences between group T and OC and SC groups. During the final phase, groups T and OS presented significant improvement, however, the group T presented better results and differed significantly from group OS regarding the number of subjects classified as Aill; the severity of muscular pain and TMJ pain; the frequency of headache and the muscles and stomatognathic functions. The group T differed significantly from the SC group but no longer differed significantly from the AC group. OMT favored a significant reduction of pain sensitivity to palpation of all muscles studied but not for the TMJs; an increased measure of mandibular range of motion; reduced Helkimo's Di and Ai scores; reduced frequency and severity of signs and symptoms; and increased scores for orofacial myofunctional conditions. PMID- 21032980 TI - Orthodontic treatment for the TMJ patient following splint therapy to stabilize a displaced disk(s): a systemized approach. Part II. AB - Orthodontic treatment for a patient who has had a displaced disk or disks and has been stabilized by anterior repositioning splint therapy presents the dentist with a difficult orthodontic problem. Frequently, there is a posterior open bite present, with the anterior teeth only occluding in the stabilized TMJ position upon removal of the splint. The current articles (Part II of II presented here) will present an organized TMJ/orthodontic diagnosis [Part I, J Craniomandib Pract2010; 28(3):193-199] and orthodontic treatment method (Part II) to properly treat these patients to a consistent stabilized occlusion compatible with the TMJ splint stabilized position. PMID- 21032981 TI - Immediate effect of the resilient splint evaluated using surface electromyography in patients with TMD. AB - The aim of this study was to analyze the immediate effect of resilient splints through surface electromyography testing and to compare the findings with the electromyographic profiles of asymptomatic subjects. The participants were 30 subjects, 15 patients with TMD (TMD Group) and 15 healthy subjects (Control Group), classified according to Research Diagnostic Criteria (RDC/TMD) Axis I. A resilient occlusal splint was made for each patient in the TMD Group from two mm thick silicon to cover all teeth. The EMG examination was performed before and immediately after installing the splint. Three tests were performed as follows: 1. Maximum Voluntary Contraction (MVC) using cotton rolls (standards test); 2. MVC in maximal intercuspation position; and 3. MVC with the splint in position. The EMG signal was recorded for five seconds. EMG indices were calculated to assess muscle symmetry, jaw torque, and impact. There was a statistically significant difference when comparing the results among the study groups. The symmetry index values in the Control Group were higher than the TMD Initial Group and similar to the TMD Group after the installation of the splint. The index values of torque were higher in TMD Initial Group when compared with the Controls. Impact values were lower than normal values in the TMD Initial Group and restored upon installation of the splint. The resilient occlusal splints may be used as complementary or adjunctive treatment of temporomandibular disorders. PMID- 21032982 TI - Mastication, EMG activity and occlusal contact area in subjects with different facial types. AB - Dentofacial morphology may affect orofacial functions, therefore the aim of the current study was to evaluate the influence of craniofacial morphology on masticatory function, occlusal contact area (OCA), and masticatory muscles activity. Seventy-eight (78) subjects were divided into three groups according to vertical facial pattern: 1. mesofacial; 2. brachyfacial; and 3. dolichofacial. Artificial material and the sieving method were used to access masticatory efficiency (ME). OCA was determined by registration of posterior teeth. Electromyographic (EMG) activity of the masseter and anterior temporal (AT) muscles was accessed bilaterally at rest and at maximal vertical clenching (MVC). ME (%) was significantly higher in brachyfacial and lower in dolichofacial subjects. Brachyfacials presented the highest OCA (mm2) followed by meso and dolichofacial subjects. The EMG of the masseter and AT at rest and at MVC showed that dolichofacial subjects presented the lowest activity values, while brachyfacial subjects presented significantly higher measurements. Craniofacial morphology affected masticatory function, OCA, and EMG activity of the masticatory muscles. PMID- 21032983 TI - Reproduction. Predicting IVF success on film. PMID- 21032984 TI - Secret medical testing. PMID- 21032986 TI - Family. Week-on, week-off parenting. PMID- 21032985 TI - Bullied to death? PMID- 21032987 TI - Behavior. Between the sheets. PMID- 21032988 TI - Estates. LABV your neighbour. PMID- 21032989 TI - Human resources. Speak up and speak for yourself. PMID- 21032990 TI - Breathing yourself to death. PMID- 21032992 TI - An orthodontic/orthopedic correction of the Class III malocclusion in young patients with a modified RPE appliance and a facemask. AB - Orthopedic appliances such as palatal expanders and facemasks have been successfully used for young patients with Class III malocclusions. A modified rapid palatal expansion (RPE) appliance in conjunction with a facemask can be used for correction of transverse and sagittal discrepancies in the initial phase of treatment for these patients. PMID- 21032991 TI - Multidisciplinary orthodontic treatment in adult patients: the future of orthodontics. AB - There is currently great demand among adult patients for aesthetic solutions. In the great majority of cases, patients present with serious oral problems in their mouths, such as over-crowding, ageneses, edentulous spaces from old extractions, periodontal problems, etc. In the face of all these problems we need interdisciplinary strategies that will help us carry out the complex and imaginative treatments that these cases require. In this article we are going to describe the interdisciplinary treatment that we provided to two adult patients. 1--On a 25 year old male patient with significant upper maxillary crowding with transversal constriction and absence of the upper right lateral incisor; through correction of the over-crowding, the maxillary constriction and rehabilitation with an implant-supported fixed prosthesis in the edentulous space, we will treat and correct this case. 2--A 29 year old male patient with agenesis of the superior canines and edentulous gap in the inferior dental arch. PMID- 21032993 TI - Correction of dental and cranial sidebend with ALF. AB - Specific characteristics of a sidebend cranial strain result from displacement of the skull base, i.e. the sphenoid and occiput. Sidebend strain has skeletal, facial and dental consequences which are described in this patient example. An asymmetric occlusion is commonly seen in conjunction with sidebend strain, where the posterior occlusion is more Class II on the sidebend side and more Class I on the opposite side. By addressing the cranial base problem with A.L.F. appliances, this case example demonstrates an effective means of restoring facial, structural balance, and correcting the malocclusion that accompanies the sidebend strain. PMID- 21032994 TI - Modifications in straight wire treatment. AB - Orthodontic treatments have been modified with each new generation of clinicians. Today the emphasis is on facial esthetics and healthy temporomandibular joints. With orthopedic treatment, we can develop dental arches to get the necessary space to align the teeth and we can reach adequate function and esthetics, all within relatively good stability. By combining two-phase treatment with low friction fixed orthodontics and super elastic wires we produce light but continuous forces and we can provide better treatment than before. These types of forces cause physiological and functional orthopedic orthodontic reactions. The purpose of this article is to demonstrate our fixed orthopedic and orthodontic approach called "Modified Straight Wire" or "Physiologic Arch Technique." This technique is very successful with our patients because it can exert slow and continuous forces with minimal patient cooperation. PMID- 21032995 TI - Tip Edge/controlled arch: systematic orthodontics. Part II. PMID- 21032996 TI - Do you talk too much? PMID- 21032998 TI - Bearing the brunt. Up to 13% of nurses victims of violence weekly: survey. PMID- 21032997 TI - Fueling the turf battle. Institute of Medicine report pushes expanded scope for nurses; docs say study draws illogical conclusions. AB - The Institute of Medicine's recommendation to give advanced practice nurses more leadership roles in primary care is stirring up plenty of controversy. "The idea that physician oversight of healthcare will be compromised plays into the worst of the public's fears about healthcare reform," said Alexander Hannenberg, left, of the American Society of Anesthesiologists. PMID- 21032999 TI - Easing the way for ACOs. Feds aim to create antitrust 'safe harbor' for new healthcare delivery model. PMID- 21033000 TI - Mulling Medicaid. Rand Paul might want to look at why the program pays for so many births. PMID- 21033001 TI - Local rules. Buffalo region works, prospers together. PMID- 21033002 TI - Still stuck on neutrality. No legislative remedy likely over Internet fair play. PMID- 21033003 TI - Climate of confrontation. Health groups urge Congress: let EPA oversee greenhouse gases. AB - Health organizations have a new cause after helping push through the reform law: climate change. They see it as a public health issue since rising temperatures can create health hazards. "Any action that interferes with or dilutes EPA's efforts will have a very negative effect on our public health," says Nancy Hughes, left, of the American Nurses Association. PMID- 21033004 TI - Glitch holds up hospital data. PMID- 21033005 TI - Shift in bond buying. Tax perks for banks behind move in hospital deals. PMID- 21033006 TI - Ready to add on. With plenty of cash, credit available, for-profits poised for more acquisitions. PMID- 21033007 TI - Neonatal anaesthesia. PMID- 21033008 TI - Practical pain management in the neonate. AB - Neonatal care is advancing to levels where more neonates are now offered more invasive interventions, exposing them to more prolonged hospital care. Consequently, the provision of effective and consistent management of pain in these neonates has become a pressing challenge. Advances in neonatal care have not only increased the number of neonates, who are exposed to noxious stimuli, but, over recent decades, also altered the patterns of exposure. Both procedural and postoperative pain remain distinct in nature, prevalence and management, and need to be addressed separately. Recent advances in the management of neonatal pain have been facilitated by improved methods of pain assessment and an increased understanding of the developmental aspects of nociception. Over the past decade, there have been some advances in the available pharmacological armamentarium, modest clarification of the risks of both untreated pain and aggressive analgesic practice and a greater recognition of non-pharmacological analgesic techniques. However, even advanced health systems fail to consistently articulate pain management policy for neonates, institute regular pain assessments and bridge the gaps between research and clinical practice. PMID- 21033009 TI - Regional anaesthesia and analgesia in the neonate. AB - A large number of published studies have shown that the use of diverse regional anaesthetic techniques is associated with high-quality pain relief following the different types of surgery and painful procedures that are commonly performed in neonatal patients. Apart from pain, few studies have examined other outcomes in this setting. Some data suggest a benefit with regional anaesthesia. In a retrospective study, Bosenberg et al. found that the use of epidural analgesia in neonatal patients undergoing tracheo-oesophageal fistula repair resulted in a reduced need for postoperative mechanical ventilation. Furthermore, epidural analgesia was found to be associated with a significant and beneficial modification of the neuroendocrine surgical stress response after major abdominal surgery in infants when compared to postoperative morphine infusions. The use of local anaesthetics in association with neonatal circumcision has also shown a benefit as neonates not treated with eutectic mixture of lidocaine and prilocaine (EMLA) or a penile block had an exaggerated pain response to later vaccinations as compared with neonates treated with a local anaesthetic technique. Finally, safety data generated from large, prospective studies and audits clearly show that the use of paediatric regional anaesthetic techniques is associated with adequate safety also in neonatal patients. In conclusion, a large variety of local and regional anaesthetic techniques can be safely used in neonatal patients. The use of such techniques must obviously be associated with sufficient knowledge about the various techniques, as well as adherence to adequate dosage guidelines and other safety precautions. However, if these prerequisites are met, regional anaesthesia may offer great advantages to our smallest and most vulnerable patients. PMID- 21033010 TI - Neonatal apnoea. AB - Premature infants have immature respiratory control that predisposes them to apnoea, haemoglobin oxygen desaturation and bradycardia. Apnoeas are loosely classified, according to the presence or absence of respiratory effort, into central, obstructive or mixed. There are a variety of conditions, in the perioperative period, that predispose an infant to apnoea, including: central nervous system (CNS) lesions, infections and sepsis, ambient temperature fluctuations, cardiac abnormalities, metabolic derangements, anaemia, upper airway structural abnormalities, necrotising enterocolitis, drug administration (including opiates and general anaesthetics) and possibly gastro-oesophageal reflux. Various monitoring techniques are discussed; the mainstay are pulse oximetry and abdominal-pressure transduction. There is some evidence of both short- and long-term complications of repeated apnoeas in the neonatal period, but the causal relationship is difficult to establish. Continuous positive airway pressure and caffeine therapy (up to 10 mg kg(-1)) are the most common treatments of neonatal apnoea. The less soluble volatile agents and regional anaesthetic techniques (without concurrent sedation) are associated with a lower incident of postoperative apnoea. PMID- 21033011 TI - Spinal anaesthesia in the neonate. AB - Postoperative apnoea in ex-premature infants is inversely proportional to gestational age at birth and postmenstrual age (PMA). Spinal anaesthesia is an important technique in ex-premature infants as it reduces the risk of postoperative apnoea, provided intra-operative sedation is avoided. Recent studies have provided more data on recommended doses of local anaesthetics for infant spinal anaesthesia as well as adjuvants used to prolong the duration of surgical anaesthesia. Spinal anaesthesia is also used for surgical procedures other than inguinal hernia repair. There are a variety of reasons why awake regional is not the preferred technique for ex-premature infants undergoing lower abdominal surgery in many centres, and there is also controversy over the appropriate anaesthetic technique for outpatient surgery in infants <60 weeks PMA. A pragmatic decision analysis on the selection of anaesthetic techniques for inguinal hernia repair in infants is presented. PMID- 21033012 TI - Neonatal ventilation. AB - Preventing ventilation-induced lung injury and bronchopulmonary dysplasia is an important goal in the care of ventilated neonates. Recently, there have been tremendous efforts to improve ventilation strategies, which aim at ventilating with a 'protective' and 'open-lung' strategy. Several different ventilation modes are now available, but it is important to note that, with regard to the neonatal pulmonary and neural outcome, there is still no clear evidence as to the superiority of one ventilation mode over another. Clinicians should bear in mind that any ventilation mode used to ventilate a neonate should be accompanied by real-time pulmonary monitoring to continuously adapt the ventilation strategy to the sudden changes in the respiratory mechanical properties of the lung. This article will describe the different ventilation modes available for neonates and highlight the importance of using a protective and open-lung ventilation strategy, even in the operating room. PMID- 21033013 TI - Neonatal fluid management. AB - Perioperative fluid management in paediatrics has been the subject of many controversies in recent years, but fluid management in the neonatal period has not been considered in most reviews and guidelines. The literature regarding neonatal fluid management mainly appears in the paediatric textbooks and few recent data are available, except for resuscitation and fluid loading during shock and major surgery. In the context of anaesthesia, many neonates requiring surgery within the first month of life have organ malformation and/or dysfunction. This article aims at reviewing basic physiological considerations important for neonatal fluid management and mainly focusses on fluid maintenance and replacement during surgery. PMID- 21033014 TI - Pulmonary hypertension of the newborn. AB - Pulmonary hypertension presenting in the neonatal period can be due to congenital heart malformations (most commonly associated with obstruction to pulmonary venous drainage), high output cardiac failure from large arteriovenous malformations and persistent pulmonary hypertension of the newborn (PPHN). Of these, the most common cause is PPHN. PPHN develops when pulmonary vascular resistance (PVR) remains elevated after birth, resulting in right-to-left shunting of blood through foetal circulatory pathways. The PVR may remain elevated due to pulmonary hypoplasia, like that seen with congenital diaphragmatic hernia; maldevelopment of the pulmonary arteries, seen in meconium aspiration syndrome; and maladaption of the pulmonary vascular bed as occurs with perinatal asphyxia. These newborn patients typically require mechanical ventilatory support and those with underlying lung disease may benefit from high frequency oscillatory ventilation or extra-corporeal membrane oxygenation (ECMO). Direct pulmonary vasodilators, such as inhaled nitric oxide, have been shown to improve the outcome and reduce the need for ECMO. However, there is very limited experience with other pulmonary vasodilators. The goals for anaesthetic management are (1) to provide an adequate depth of anaesthesia to ablate the rise in PVR associated with surgical stimuli; (2) to maintain adequate ventilation and oxygenation; and (3) to be prepared to treat a pulmonary hypertensive crisis--an acute rise in PVR with associated cardiovascular collapse. PMID- 21033015 TI - Tracheo-oesophageal fistula (TOF) and oesophageal atresia (OA). AB - Tracheo-oesophageal fistula (TOF) and oesophageal atresia (OA) represent a series of anatomical abnormalities presenting for emergency surgery in the neonatal period. They present the anaesthetist with cardio-respiratory challenges in the preoperative, intra-operative and postoperative phases. In addition to the consequences of the pathology itself, co-morbidities are very common, which superimpose further considerations. The basic science, anatomy and genetics are discussed as well as the clinical presentation, perioperative management, controversies and complications. The evidence for optimum management is based mostly on expert opinion; there are very few large randomised controlled trials concerning many areas of perioperative management. PMID- 21033016 TI - Vascular access in the neonate. AB - Up to recently, inserting venous or arterial 'lines' in the neonate was essentially based on clinical skill and experience. The recent advent of portable ultrasound (US) machines with paediatric probes has resulted in the development of new approaches that, if correctly learned and used, should allow quicker and safer vascular access in this population. Both classic and new techniques are reviewed on the basis of literature and authors' experience. PMID- 21033017 TI - The pharmacology of anaesthetics in the neonate. AB - Neonatal anaesthesia dosing needs to be based on physiological characteristics of the newborn, pharmacokinetic/pharmacodynamic considerations and the adverse effects profile. Disease processes and treatments in this group are distinct from adults. Absorption, distribution and clearance are altered because of immaturity of enzyme, anatomical or physiological systems resulting in extensive variability of drug disposition in neonates. This is further compounded by pharmacogenomic influences. Population and physiological-based pharmacokinetic modelling have improved understanding of maturation and subsequent dose approximation. Postmenstrual age is a reasonable measure for maturation, although postnatal age may also have an impact. The neonatal response to drugs is also altered. Although neuromuscular monitoring is robust, there remains a need for other clinically applicable tools to assess pharmacodynamics that can provide effect feedback. In neonatal anaesthesia, a specific focus of interest is tools to assess depth of anaesthesia, sedation and pain. These tools have potential to improve effectiveness and safety. PMID- 21033018 TI - The impact of the perioperative period on neurocognitive development, with a focus on pharmacological concerns. AB - Mounting evidence from animal studies has implicated that all commonly used anaesthetics and sedatives may induce widespread neuronal cell death and result in long-term neurological abnormalities. These findings have led to serious questions regarding the safe use of these drugs in young children. In humans, recent findings from retrospective, epidemiological studies do not exclude the possibility of an association between surgery with anaesthesia early in life and subsequent learning abnormalities. These results have sparked discussions regarding the appropriate timing of paediatric surgery and the safe management of paediatric anaesthesia. However, important questions need to be addressed before findings from laboratory studies and retrospective clinical surveys can be used to guide clinical practice. This article summarises the currently available preclinical and clinical information regarding the impact of anaesthetics, sedatives, opioids, pain and stress, inflammation, hypoxia-ischaemia, co morbidities and genetic predisposition on brain structure and long-term neurological function. Moreover, this article outlines the putative mechanisms of anaesthetic neurotoxicity, and the phenomenon's implications for clinical practice in this rapidly emerging field. PMID- 21033019 TI - Use of pharmaceuticals 'off-label' in the neonate. AB - Neonates are frequently not studied in the development of a novel pharmacological agent. With lack of data to support safe and effective use of a new agent in this population, sponsors will not receive approval for labelling the agent for use in this age group from the United States Food and Drug Administration (USFDA). This causes a significant conundrum for the clinician. Neonates are often precluded the benefits of new pharmaceuticals until investigators begin to report their clinical experience with novel agents. This article provides the clinician with an introductory understanding of the approval process of pharmaceuticals in the United States by USFDA. Models of clinical trial design are noted. Examples of anaesthetic and non-anaesthetic agents and their development and use are discussed as either 'labelled' or 'off-label' indications. PMID- 21033020 TI - Neonatal resuscitation. AB - Neonatal resuscitation techniques are evolving. More sophisticated methods of monitoring have emerged and current practices have been challenged. It is recognised that most newborns will require only gentle assistance to facilitate the transition from intrauterine life. The routine use of suction and oxygen supplementation is no longer recommended and the effectiveness of current methods of delivering ventilatory support has been questioned. The importance of effective use of masks and optimising tidal ventilation rather than pressure generation is emphasised. Newer oximetry technologies and the routine use of capnography may facilitate clinical assessment even during active resuscitation. Methods of warming infants have become increasingly effective and the use of servo-control is emphasised to prevent overheating. Evidence to support therapeutic hypothermia for the birth-asphyxiated baby is solid and cooling should be considered a standard of care. The next revision of the International Liason Committee on Resuscitation (ILCOR) Guidelines is eagerly awaited in 2010. PMID- 21033021 TI - Evidence for the need for anaesthesia in the neonate. AB - Neonates are both capable of experiencing pain and memory formation, albeit implicit memory. During surgical procedures, insufficient ablation of the stress response and possible implicit memory formation of intra-operative events might result in adverse early and long-term outcomes. Neonates deserve the same respect as adult patients. It is thus the responsibility of the anaesthetist to provide sufficient anaesthesia for neonates undergoing surgery. A critical approach in weighing the risks and benefits of exposing a neonate to anaesthesia is prudent, and truly elective surgery should be delayed. PMID- 21033022 TI - Hypopharyngeal extrusion of 2.5 feet (76 cm) of polytetrafluoroethylene (Gore Tex): initial laser-assisted office-based removal and micropharyngeal completion. AB - Extrusion of an implant after medialization laryngoplasty is unusual and warrants removal. Most commonly, it extrudes through the laryngeal introitus, but rarely, it extrudes through the pyriform sinus. A case report in which 2.5 feet (76 cm) of polytetrafluoroethylene (Gore-Tex) was removed from an 80-year-old female patient is presented to evaluate factors that led to this surgical complication and strategies that solved the problem. Because of the patient's multiple medical problems, initial removal of the foreign body was attempted in the office with topical anesthesia. When the Gore-Tex was noted to be lodged in the laryngeal parenchyma, it was severed at the edge of the pyriform sinus to stabilize the airway. Subsequently, microlaryngoscopic-controlled completion removal was done in the operating room with general anesthesia. The patient healed uneventfully with no further sequelae. Analysis of this case illustrates a number of factors leading to a rare iatrogenic foreign body complication. Office-based removal of the Gore-Tex implant evolved into a unique scenario in which the rapid use of a fiber-based laser to divide the foreign body facilitated stabilizing the airway to allow for elective completion removal in a controlled fashion. PMID- 21033023 TI - Balloon catheter sinuplasty and adenoidectomy in children with chronic rhinosinusitis. AB - OBJECTIVES: Adenoidectomy is the first step in the surgical management of children with chronic rhinosinusitis (CRS). Adenoidectomy, however, is only effective in half of these children. Although endoscopic sinus surgery is effective for CRS, there is concern for facial growth retardation and major complications. We propose that balloon catheter sinuplasty (BCS) is a minimally invasive, effective procedure in the treatment of pediatric CRS. METHODS: We undertook a nonrandomized, controlled, prospective review of children with failed medical management of CRS who underwent BCS or adenoidectomy. Outcomes were assessed at 1 year of follow-up and were based on SN-5 scores and the need for revision surgery. RESULTS: Forty-nine children who satisfied the inclusion criteria were reviewed. Thirty of the children had BCS. The age range was 4 to 11 years (mean, 7.7 years), and the mean computed tomography score (Lund-Mackay system) was 7.5. Twenty-four of the 30 patients (80%) who underwent BCS showed improvement of their symptoms after 12 months of follow-up, compared with 10 of the 19 patients (52.6%) who underwent adenoidectomy (p < 0.05). A multivariate analysis using logistic regression analysis with age, sex, asthma, and computed tomography score as covariables showed that BCS was also more effective than adenoidectomy in older children. None of the other variables showed statistical significance. CONCLUSIONS: Balloon catheter sinuplasty offers a procedure that is more effective than adenoidectomy and less invasive than endoscopic sinus surgery in the treatment of pediatric CRS. PMID- 21033024 TI - Use of ICF in assessing the effects of Meniere's disorder on life. AB - OBJECTIVES: We sought to determine the value of the World Health Organization's International Classification of Functioning, Disability and Health (ICF) in subjects with Meniere's disorder in relation to their quality of life. METHODS: We asked 228 members of the Finnish Meniere Federation to report the effects that Meniere's disorder had on their lives. The replies were classified on the basis of the ICF classification and related to the EuroQol 5D score and disease specific impact. Logistic regression and decision tree analyses were used to determine the relationships. RESULTS: Seventy percent of the patients listed impairments, 39% activity limitations, 47% participation restrictions, 16% effects on environmental contextual factors, and 28% effects on personal contextual factors. The EuroQol 5D score was explained by reported vertigo, anxiety, fatigue, restriction of life, and communication problems. The disease specific impact was explained by episodes of vertigo, fatigue, communication problems, inability to work, restriction of life, and uncertainty of life. Both analysis models provided the same outcome variables, although the decision tree separated the results better (80%) into correct classes than did logistic regression analysis (60%). CONCLUSIONS: Self-reported participation restriction, activity limitation, and personal contextual factors describe the limitations of general life in subjects with Meniere's disorder. The use of the ICF classification provides an instrument that can be used in enablement of subjects with Meniere's disorder. PMID- 21033025 TI - Methicillin-resistant Staphylococcus aureus laryngitis. AB - Infections due to methicillin-resistant Staphylococcus aureus (MRSA) have become more prevalent, in part because of the emergence and spread of community-acquired MRSA. This trend is particularly concerning because of the significant rates of morbidity and mortality associated with MRSA infections, and because MRSA strains are often resistant to many classes of antibiotics. Reports of infections of the head and neck, including wound infections, cellulitis, sinusitis, otitis media, and otitis externa, are well documented. However, to our knowledge, there have been no reports of bacterial laryngitis due to MRSA. We report the first published case of bacterial laryngitis caused by MRSA. PMID- 21033027 TI - Forestier disease: single-center surgical experience and brief literature review. AB - OBJECTIVES: We describe the experience of our otolaryngology department in the treatment of Forestier disease, particularly regarding the diagnostic process, surgical treatment, and postoperative outcomes. METHODS: The charts of 12 patients who underwent surgical treatment of Forestier disease between January 1, 2003, and January 1, 2009, were analyzed. All patients were subjected to clinical, radiologic, and endoscopic evaluation that confirmed the presence of cervical osteophytes. All patients were treated by a right-sided prevascular transcervical approach to remove cervical osteophytes. A literature review on Forestier disease was also carried out. RESULTS: One case of immediate postoperative hemorrhage was reported. During the postoperative follow-up, ranging from 1 to 5 years, all patients underwent cervical radiography and fiberoptic laryngoscopy that confirmed no evidence of recurrence, and all patients remained asymptomatic. CONCLUSIONS: A prevascular transcervical right sided approach seems to be an effective treatment for surgical removal of hyperostosis in Forestier disease, with an acceptable rate of complications and recurrence. PMID- 21033026 TI - Neck surface electromyography as a measure of vocal hyperfunction before and after injection laryngoplasty. AB - OBJECTIVES: The goal of this preliminary study was to determine whether neck surface electromyography (sEMG) is sensitive to possible changes in vocal hyperfunction associated with injection laryngoplasty, particularly with respect to alterations in the degree of vocal hyperfunction. METHODS: Thirteen individuals undergoing office-based injection laryngoplasty for glottal phonatory insufficiency were prospectively studied with a battery of acoustic, aerodynamic, endoscopic, and anterior neck sEMG assessments before the procedure and approximately 1 week afterward. RESULTS: Anterior neck sEMG values were not significantly reduced (p < 0.05) after the procedure; however, perceptual ratings of strain and false vocal fold compression were both significantly reduced, reflecting a decrease in vocal hyperfunction. CONCLUSIONS: The results do not support the use of anterior neck sEMG measures to assess vocal hyperfunction, and place into question the use of some other measures (estimates of anterior posterior supraglottic compression, quantitative measures of anterior-posterior and false vocal fold supraglottic compression, and acoustic vowel rise times) that have been considered reflective of vocal hyperfunction. PMID- 21033028 TI - Elastic fibers in Reinke's edema. AB - OBJECTIVES: We describe the distribution of elastic system fibers in the superficial layer of the lamina propria of Reinke's edema, as compared with normal vocal folds. METHODS: Weigert's resorcin-fuchsin stain after oxidation with 10% oxone was used to study the arrangement of elastic fibers. The findings were categorized and afterward compared with the severity of Reinke's edema. RESULTS: Analysis of 20 specimens of vocal folds with Reinke's edema showed that the network of thin elastic fibers in Reinke's space lost their undulated appearance and had a tangled aspect. In addition, these fibers were no longer parallel to the epithelial basement membrane, but had a random distribution scattered throughout Reinke's space. The elastic fiber network immediately below the epithelial basement membrane also appeared more fragmented in Reinke's edema because of some alteration in organization combined with the 5-microm-thick histologic sectioning plane. No significant difference in the degree of elastic system fiber disarrangement was observed between severity grades II and III (p = 0.382). Large areas of disarrangement were predominant (80% of cases). CONCLUSIONS: The disarrangement of elastic fibers in Reinke's edema may cause insufficient tissue resistance and resilience, contributing to the hypermobility observed in Reinke's edema. PMID- 21033029 TI - Prevalence of acoustic neuroma associated with each configuration of pure tone audiogram in patients with asymmetric sensorineural hearing loss. AB - OBJECTIVES: The criteria have not yet been established for identifying the configuration of a pure tone audiogram constituting abnormal results that warrant further investigation. The purpose of this study was to determine the prevalence of acoustic neuroma associated with each configuration of the pure tone audiogram in patients with asymmetric sensorineural hearing loss (SNHL). METHODS: We performed a retrospective chart review of 500 patients 15 years of age or older who had asymmetric SNHL and had undergone magnetic resonance imaging. RESULTS: The prevalence of acoustic neuroma in these patients was 2.6% (13 of 500). The prevalence of acoustic neuroma in each audiometric configuration was as follows: 7.1% (3 of 42) for a basin-shaped loss (odds ratio [OR] versus overall prevalence, 2.88; p = 0.23; 95% confidence interval [CI], 0.79 to 10.54), 4.7% (5 of 107) for a flat loss, 3.4% (2 of 58) for total deafness, 2.9% (1 of 34) for a high-frequency sloping audiogram, and 2.5% (2 of 81) for a high-frequency steep audiogram. The prevalence in patients with nonimproving idiopathic sudden deafness was 8.1% (OR, 3.29; p = 0.06; 95% CI, 1.13 to 9.55). CONCLUSIONS: In conclusion, 2.9% to 8.1% of patients with a characteristic configuration of the pure tone audiogram and symptoms of nonimproving or progressive idiopathic sudden deafness may have acoustic neuroma. PMID- 21033030 TI - Balloon dilation for recurrent stenosis after pediatric laryngotracheoplasty. AB - OBJECTIVES: We assessed the safety and efficacy of balloon dilation as treatment for recurrent stenosis after pediatric laryngotracheoplasty. METHODS: We studied a retrospective case series at an academic tertiary care children's hospital. We included all patients under the age of 18 years with subglottic or tracheal stenosis treated at our institution with balloon dilation between June 2007 and April 2009. The records were analyzed for patient demographics, presenting symptoms, surgical technique, and airway description. The outcome measures were airway diameter, postoperative symptoms, tracheotomy status, and complications. RESULTS: Ten patients (9 with subglottic stenosis and 1 with tracheal stenosis) underwent 20 balloon dilation procedures without complication. The average age at the time of the procedure was 17 months (range, 3 months to 9 years). The patient presenting symptoms were stridor in 7 cases and tracheotomy in 3 cases. Vascular balloons (diameter range, 6 to 12 mm; length, 20 mm) were inflated to 10 to 12 cm H2O pressure for an average of 40 seconds (range, 10 to 120 seconds). Each procedure consisted of 1 to 3 dilation cycles. The immediate postdilation airway area increased by an average factor of 4.9 (range, 1.9 to 9). Six patients had repeat procedures with an average interval between dilations of 67 days (range, 6 to 337 days). Stridor was eliminated or greatly improved in all patients on the first postoperative day; 7 patients sustained this benefit, with an average follow-up time of 10 months (range, 4 to 23 months). Six of the 10 patients had undergone previous laryngeal reconstruction (age range, 3 months to 4 years). Of these 6, 3 have no tracheotomy, with a mean follow-up of 12.5 months. The 3 children who benefited the least from dilation were noted to have more diffuse and chronic inflammation of the larynx in comparison to the responders. CONCLUSIONS: This case series suggests that balloon dilation is a relatively safe and effective procedure. It may be particularly well suited to recent stenosis after laryngotracheal reconstruction. PMID- 21033031 TI - Dislocation of stapes with footplate fracture caused by indirect trauma. AB - We report the first case of isolated stapedial dislocation caused by indirect head trauma, and present imaging and surgical findings in the case of a 25-year old woman who suffered hearing loss and dizziness after head trauma caused by a traffic accident. The pure tone average was 60 dB, with an air-bone gap of 50 dB. The stapedial reflex was positive with the probe on the affected ear. Computed tomography scans revealed a longitudinal fracture of the temporal bone and a dislocated stapedial superstructure in the tympanic cavity, adhering to the tympanic membrane. During surgery, it was found that the stapes was broken at the base of the posterior crus and at the anterior one third of the footplate and that the stapedial superstructure was dislocated outward and downward, with the anterior one third of the footplate adhering to the tympanic membrane. The stapedial tendon was connected to the superstructure. Ossicular chain reconstruction was performed with success. In the present case, two mechanisms may have acted together: 1) an increase in perilymphatic pressure that caused the footplate to fracture, and 2) a distorting force that broke the posterior crus, disconnecting the incudostapedial joint, and finally dislocating the stapedial superstructure together with the anterior part of the footplate. PMID- 21033032 TI - Value of barium swallow studies in predicting the response to rabeprazole in elderly patients with laryngopharyngeal reflux disease and nonerosive reflux disease in particular. AB - OBJECTIVES: Laryngopharyngeal reflux disease (LPRD) is an important cause of throat discomfort in the elderly. Our objective was to investigate the usefulness of barium swallow studies for the diagnosis of LPRD. METHODS: The subjects were 59 patients at least 60 years of age with LPRD suspected on laryngoscopic findings. We evaluated esophageal clearance using a barium swallow study and the upper gastrointestinal tract endoscopic findings of gastroesophageal reflux disease according to the revised Los Angeles classification, and correlated these findings with the effect of rabeprazole, a proton pump inhibitor. RESULTS: Among subjects with positive reflux findings in the esophageal phase of the barium swallow, rabeprazole was significantly effective (p = 0.0025). To identify nonerosive reflux disease, we analyzed the 50 cases with a negative Los Angeles classification of upper gastrointestinal tract endoscopic findings. Rabeprazole was again significantly effective in patients with positive findings for esophageal reflux (p = 0.0025). CONCLUSIONS: Among elderly patients with suspected LPRD, there was a positive correlation between impaired esophageal clearance on the barium swallow study and the effectiveness of rabeprazole. The barium swallow study could be a screening test for LPRD in elderly patients with throat discomfort. PMID- 21033033 TI - Epiglottoplasty for reconstruction of defects after laryngectomy with partial pharyngectomy. AB - OBJECTIVES: We present a novel use of sliding epiglottoplasty as an alternative method for closing mucosal defects in selected laryngectomies with partial pharyngectomy. METHODS: Sliding epiglottoplasty as described and advocated by Sedlacek, Bouche, Kambic, and Tucker for reconstruction in partial laryngectomies was used to close the defects after laryngectomy with partial pharyngectomy in 17 patients with advanced hypopharyngeal cancers as primary therapy (16 patients) and as post-radiochemotherapy therapy (1 patient). RESULTS: All reconstructions were successful. Primary closures were achieved without additional morbidity, there were no pharyngocutaneous fistulas, and all patients resumed deglutition. Ten patients acquired esophageal speech, speech valves were inserted in 5 cases, and 2 patients required the use of an electrolarynx. CONCLUSIONS: If the oncological circumstances allow its preservation in laryngectomy with partial pharyngectomy, the epiglottis is an ideal structure for closing the defect; it is a local tissue with shape, thickness, rigidity, and borders that match the recipient site. In comparison to distant pedicled or free microvascular flaps, the epiglottoplasty is a shorter procedure, requires a smaller surgical team, results in less trauma, has a lower incidence of complications, and enables faster recovery. It is surprising that this elegant, successful, and generally accepted larynx preservation procedure has not been recognized as useful for larger reconstructions. PMID- 21033034 TI - Neurosarcoidosis affecting the vagus nerve. AB - OBJECTIVES: Our objective was to review patients who presented to our medical center with a diagnosis of neurosarcoidosis affecting the vagus nerve and to present symptoms, progression, treatments, and outcome. METHODS: We performed a chart review of patients who presented to our medical center in the past 10 years with a diagnosis of neurosarcoidosis specifically affecting cranial nerve X. RESULTS: A chart review of 53 patients revealed only 4 with findings suggestive of vagal neurosarcoidosis. All were male and had a mean age of 50 years (range, 42 to 57 years) at presentation of symptoms. Two of the 4 patients presented initially with cough, 1 had recurrent syncope, and another presented with left facial pain. Vagus nerve involvement included vocal fold paresis or paralysis in all 4 patients, 2 of whom reported coughing with exposure to various odors and 2 of whom were found to have a unilateral palatal weakness. All but 1 had positive findings on magnetic resonance imaging of the head. CONCLUSIONS: Neurosarcoidosis involving the vagus nerve is a rare finding, but should be considered in the differential diagnosis of vocal fold paresis or paralysis. PMID- 21033035 TI - Sphenoid sinus pneumatization and its relation to bulging of surrounding neurovascular structures. AB - OBJECTIVES: We investigated the bulging and dehiscence of neurovascular structures in the sphenoid sinus and their relationships to the pneumatization of the sphenoid sinus. METHODS: One hundred sagittally hemisected cadaveric heads were examined. The degree of pneumatization of the sphenoid sinus was determined. Bulging and dehiscence of the internal carotid artery (ICA), optic nerve, maxillary nerve, and vidian nerve were examined, and the distances between these structures and the anterior or superior wall of the sphenoid sinus were measured. Additionally, the degree of bony thickness over these structures was determined. RESULTS: The prevalences of bulging of the optic nerve, segments 1 and 3 of the ICA, and the maxillary and vidian nerves were 56%, 34%, 65%, 41%, and 52%, respectively. The greater the degree of pneumatization, the more frequently did the structures bulge into the sphenoid sinus. The optic nerve was found to be in close proximity to the anterior and superior walls of the sphenoid sinus. The bone over the surrounding structures was very thin, especially for the complete sellar type. CONCLUSIONS: The prevalence of bulging of the optic nerve, the ICA, and the maxillary and vidian nerves increased in proportion to the degree of sphenoid sinus pneumatization. PMID- 21033036 TI - [The expression and significance of ANXA2 in human glioma]. AB - AIM: to investigate the relation between the expression of ANXA2 in human glioma and its pathological grades, and research the possibility that if ANXA2 could be as a useful diagnostic marker for glioma. METHOD: Semi-quantity RT-PCR and immunohistochemistry were proceeded fro corresponding specimens to detect the level of ANXA2 and ANXA2mRNA. RESULTS: In RT-PCR, the expression level of ANXA2mRNA in glioma was higher than that in surrounding brain tissue. (P < 0.05), as the same, in immunohistochemistry, the expression level of ANXA2 in glioma is higher than that is surrounding brain tissues (P< 0.05). CONCLUSION: ANXA2 expression was much higher in glioma samples than in the surrounding brain tissues, and positive correlation between its expression and pathological grades was found. It could be used as an assistant diagnostic index for glioma. PMID- 21033037 TI - Primary health on the Medline radar. PMID- 21033038 TI - Tales from Vienna. The world's AIDS community converges upon Vienna for the International AIDS Conference. PMID- 21033039 TI - Renewed hope. "Efforts to discover a cure for HIV take on a new life--but it still won't be easy. PMID- 21033040 TI - Getting closer. Studies take aim at eradicating the virus. PMID- 21033041 TI - Plotting a strategy. Interview by Jeff Berry. PMID- 21033042 TI - Republicans to ADAP's rescue? In the effort to end ADAP waiting lists, Democrats in the Senate are MIA. PMID- 21033043 TI - Virtual you. Tips for writing your personal profile. PMID- 21033044 TI - Status symbols. Cleveland rocks at fighting stigma and discrimination. PMID- 21033045 TI - Use of the dry angle isolation adjunct in general dentistry: a clinical approach. AB - The dry angle is a thin, triangle-shaped piece of moisture-absorbing cellulose that is placed over the buccal mucosa. It absorbs parotid gland saliva and some mandibular saliva, and helps to maintain a dry working field. It is an adjunct to rubber dam isolation and can facilitate dry field isolation in ways that cotton rolls cannot. Its thinness allows it to be placed in the thin space between the maxillary second molars and the ramus aspect of the mandible and sometimes it may be the most practical tool for isolating second molars for bonding or cementation procedures. When slightly moistened with parotid saliva, the dry angle adheres to the surface of the buccal mucosa. It replaces the flabby surface of the buccal mucosa with the stif surface of the dry angle. This prevents suctioning of the mucosa by the high volume evacuator (HVE) suction tip, aids in retraction of the mucosa and increases the number of ways that instruments can be positioned intraorally without obstruction from the HVE suction tube. This article explains the clinical techniques and use of the dry angle in general dentistry. PMID- 21033046 TI - Bad leadership. PMID- 21033047 TI - Proudly serving. PMID- 21033048 TI - A better kind of sealant. PMID- 21033049 TI - Yes, the American Mosquito Control Association is ready for the new millennium: 2010 presidential address, March 29, 2010. PMID- 21033050 TI - Description of Himalayan mosquito pupae II. Ochlerotatus shortti and Oc. elsiae. AB - The pupae of Ochlerotatus shortti and Oc. elsiae are described and illustrated. These species occur in the Himalaya Mountains at middle range altitudes. Characters to recognize each are explained. PMID- 21033051 TI - Immature mosquitoes of Serra do Mar park, Sao Paulo State, Brazil. AB - With the objective of providing knowledge about the natural habitat of mosquito larvae, we conducted a study on the culicid fauna and identified larval habitat types at 3 different locations in the Serra do Mar State Park, Brazil, over the 12 months of 1991. We collected 1,425 larvae belonging to 23 species, of which the most frequent were Culex iridescens, Culex spp., Limatus durhami, and Trichoprosopon pallidiventer. The mosquito larval habitats presenting the greatest densities of specimens were bamboo, bromeliads, rubber boots, and streams. We observed that the culicids used a variety of containers as larval habitats and bred under a diversity of ecological conditions. Most of the habitats were natural, formed by bamboo, bromeliads, streams, and depressions in the ground and in rocks, along with artificial habitats consisting of rubber boots and abandoned metal cans. Seven species occurred preferentially in the internodes of closed bamboo stems, 6 in internodes of open stems, and 4 in bromeliads. PMID- 21033052 TI - Studies on hibernating populations of Culex pipiens from a West Nile virus endemic focus in New York City: parity rates and isolation of West Nile virus. AB - A 3-year study was undertaken to examine the parity status, survival, and prevalence of West Nile virus (WNV) in overwintering populations of Culex pipiens pipiens collected from a hibernaculum located in a WNV endemic region in New York City. Nearly 6,000 females were collected from December through April. Parity rates were highest among females collected in December and January, ranging from 12.3% to 21.9%, depending on the year. In each year of the study, the proportion of parous females declined significantly during the course of the winter; the percentage of parous females found in April ranged from 0.9% to 10%. Results provide unequivocal evidence that parous Cx. p. pipiens females from this region of the northeastern US enter hibernacula in the fall in comparatively high proportions not previously recognized for this species, and while these females experience significant mortality during the winter, some survived to April to emerge in the spring. The absence of any detectible blood remnants in overwintering females reaffirms that blood feeding does not occur among diapausing females during the winter. The possibility that a portion of the diapausing population may be autogenous as a result of hybridization with sympatric belowground populations of Cx. p. pipiens "form molestus" is discussed. A single isolation of WNV was obtained in Vero cell culture from a pool of 50 females collected on January 11, 2007, representing an infection prevalence of 0.07% in the overwintering population in 2007 (n = 1,370 mosquitoes, 33 pools). No isolations of WNV were made from mosquitoes collected in 2008 (n = 1,870 mosquitoes, 190 pools) or 2009 (n = 1,767 mosquitoes, 184 pools). Findings provide further evidence for local overwintering of WNV in diapausing Cx. p. pipiens, albeit at very low rates, consistent with the paucity of WNV-positive mosquitoes detected in June and early July despite the emergence of females from hibernacula in early May in this region. PMID- 21033053 TI - Strain-specific differences in mating, oviposition, and host-seeking behavior between Wolbachia-infected and uninfected Aedes albopictus. AB - Wolbachia are maternally inherited bacteria that cause various reproductive alterations in their arthropod hosts, including cytoplasmic incompatibility. In this study, we compared mating, oviposition, and host-seeking behavior of Wolbachia-infected (Houston [HOU], Gainesville [GNV]) and Houston uninfected (HT1) Aedes albopictus. In mating assays with virgin mosquitoes, mating success of Wolbachia-infected males was significantly higher than uninfected strains. Mating success was highest with HOU males exposed to infected (95%) and uninfected females (100%), and lowest with HT1 males exposed to infected (20%) and uninfected (25%) females. Results suggested that Wolbachia infection may influence the reproductive behavior of this mosquito. There were no clear differences in oviposition responses between strains, with all strains ovipositing significantly more often on hay infusion and larval rearing water than on water controls and least frequently on 4-methylphenol. Strains of Ae. albopictus females were host-seeking a human when given a choice. Responses to a human arm, acetone, CO2, and dichloromethane were generally higher from the Houston strains than from the GNV strain. Responses of HOU and HT1 females differed from GNV with greater responses to the arm and CO2. PMID- 21033054 TI - Epidemiology of West Nile virus: a silent epiornitic in Northern Delaware in 2007 without associated human cases. AB - ABSTRACT. We performed a 2-year longitudinal study (2006-2007) of West Nile virus (WNV) infections in wild birds, mosquitoes, and sentinel chickens at 6 WNV endemic sites in northern Delaware. We determined virus infection rates of Culex pipiens and other mosquito vectors as well as seroprevalence and antibody titers of amplifying hosts. Endemicity status varied widely among the 6 sites based on 3 criteria-mosquito infections, sentinel chicken seropositivity, and wild bird seropositivity. A highly endemic site would display at least 2 of the 3 criteria during each year of the study, while a site with just 1 positive criterion was considered to have low endemicity. Culex pipiens was the principal vector detected at 2 highly endemic sites in 2006 vs. 1 site in 2007. However, in 2006, we also found 2 other WNV-positive vector species as well as an unidentifiable Culex species at 1 highly endemic site, suggesting increased activity at the end of the 1st year of the study. Wild birds were early indicators of WNV at highly endemic sites in mid-July to early August of both 2006-2007. Mosquitoes were positive in mid- to late August, appearing concurrently with seroconverted sentinel chickens, with wild resident birds appearing approximately 4 wk prior to those indicators. Of birds tested with n > or = 9, Northern cardinals had the highest seropositivity rates (47%) followed by Carolina wrens (19%), house sparrows (13%), American robins (13%), tufted titmice (11%), and gray catbirds (9%). The overall seropositive rates in trapped birds increased from 5.0% in 2006 to 20.0% in 2007, while the geometric mean titers of all positive birds increased from 1:34 to 1:47 during the comparable periods. Based on these results, we suggest that an epiornitic in birds occurred in 2007, but that greatly reduced abundance of mosquito vectors caused by an extreme drought largely precluded human infection. PMID- 21033055 TI - The effect of Mosquito Magnet Liberty Plus trap on the human mosquito biting rate under semi-field conditions. AB - This study evaluated the efficacy of a commercially available mosquito trap, the Mosquito Magnet Liberty Plus (MM), in reducing human biting rates under semi field conditions when used alone or with different types of repellents. The MM trap significantly reduced the human biting rate with both laboratory-reared Culex quinquefasciatus and Anopheles gambiae sensu stricto. The MM trap catch did not increase when a mosquito coil was burned but did significantly increase when a skin repellent was applied to the human bait. Microencapsulated repellent ankle bands did not increase the MM trap catch with either Cx. quinquefasciatus or An. gambiae s.s., although its combination with the trap was more effective at reducing bites by Cx. quinquefasciatus. The absence of the commercial attractant Lurex3 in traps significantly lowered the catch efficiency of Cx. quinquefasciatus even when the skin repellent was applied to volunteers. The results from this study showed that the use of a skin repellent and an attractant baited trap can significantly reduce the human biting rate of both nuisance biting mosquitoes and malaria vectors. Further work is required to investigate how this push-pull system would work in a field environment. PMID- 21033056 TI - Field efficacy of granular formulations of Bacillus thuringiensis Israelensis- strain AM65-52 against floodwater mosquitoes in Poland and Germany. AB - This paper presents results of studies evaluating the efficacy of various granular formulations of VectoBac (Bacillus thuringiensis israelensis de Barjac [Bti] H-14 strain AM65-52) against immature mosquitoes in 2 distinct habitats in Poland and Germany. Meadows intermittently flooded with sewage water in the city of Wroclaw, Poland, provide ideal habitats for immature stages of Aedes caspius, Ae. vexans, and Culex pipiens pipiens. Helicopter applications of VectoBac G and VectoBac TP sand granules (VectoBac TP-SG) at rates of 5 and 10 kg/ha to the meadows resulted in between 70.9% and 97.4% larval mortality. In Germany, some swampy woodlands in the upper Rhine Valley provide ideal habitats for snowmelt mosquitoes, Aedes cantans, Ae. punctor, Ae. rusticus, and Ae. communis. Ground applications of VectoBac G, VectoBac TP-SG, and VectoBac WG IcyPearls (VectoBac WG-IP) were made to these habitats when the water temperature was approximately 7 degrees C. Larval mortality at 7-day post-application ranged from 90.9% (VectoBac TP-SG: 10 kg/ha) to 98.0% (VectoBac WG-IP: 15 kg/ha). In a separate microcosm trial within the same habitat, all 3 granule formulations controlled larvae of Ae. cantans for 3 wk. PMID- 21033057 TI - Control of Culicoides sonorensis (Diptera: Ceratopogonidae) blood feeding on sheep with long-lasting repellent pesticides. AB - Culicoides sonorensis is the primary vector of bluetongue and epizootic hemorrhagic disease viruses in North America. Bluetongue disease is one of the most economically important arthropod-borne diseases of sheep in North America, because it causes significant morbidity and mortality and can lead to local quarantines and international trade restrictions. Long-lasting repellent pesticides could be applied to sheep as they are moved down from mountain pastures to protect them from biting midges until the 1st frost. We tested long lasting pesticides on sheep as repellents against C. sonorensis. Both Python ear tags with 10% zeta-cypermethrin (9.8 g/tag) synergized with 20% piperonyl butoxide (PBO) and a 12-ml low-volume spray application of ready-to-use sheep insecticide (Y-TEX) with 2.5% permethrin and 2.5% PBO in an oil-based formulation were repellent to C. sonorensis for at least 3-5 wk after a single application. PMID- 21033058 TI - Mosquito vector biology and control in Latin America--a 20th symposium. AB - The 20th Annual Latin American Symposium presented by the American Mosquito Control Association (AMCA) was held as part of the 76th Annual Meeting in Lexington, KY, in March 2010. The principal objective, as for the previous 19 symposia, was to promote participation in the AMCA by vector control specialists, public health workers, and academicians from Latin America. This publication includes summaries of 40 presentations that were given orally in Spanish or presented as posters by participants from 5 countries in Latin America, the United Kingdom, and the USA. Topics addressed in the symposium included: surveillance, chemical and biological control, and insecticide resistance associated with Aedes aegypti; distribution, behavior, and control of Culex; bionomics, ecology, and chemical and biological control of Anopheles vectors of malaria; insecticide resistance; and studies of dengue, West Nile virus, and Triatoma. PMID- 21033060 TI - Checklist of mosquitoes in Savanna Portage State Park, north-central Minnesota. AB - A faunal survey of mosquitoes was conducted in 1988 and 1989 at Savanna Portage State Park in north-central Minnesota (Aitkin County). Adults were sampled by sweep net around collectors, aspirator in vegetation, and CO2 traps in the park. Larvae were taken with dipper from various larval habitats. A total of 32 species were detected, including 16 new records for Aitkin County, MN. Prior to this survey, Aedes decticus and Culiseta melanura were reported in Minnesota once previously. PMID- 21033059 TI - First report of Aedes albopictus and other mosquito species in Morelos, Mexico. AB - Aedes albopictus, Culex corniger, Cx. restuans, and Toxorhynchites theobaldi are reported for the first time for the Mexican State of Morelos. The updated list of species reported is also presented. PMID- 21033061 TI - Status of Aedes japonicus in the Metropolitan Mosquito Control District, Minnesota. AB - ABSTRACT. The Asian exotic mosquito Aedes japonicus was 1st collected in Minnesota in 2007 and was well established in parts of the Metropolitan Mosquito Control District (MMCD) by 2008. Surveillance strategies were devised for 2009 to track the expansion of its range through MMCD and to direct control efforts. Sampling of larvae from container and tire habitats was the primary method used to document Ae. japonicus presence, but larvae were found in other habitats as well. Adult Ae. japonicus were collected by vacuum aspirator, gravid trap, and New Jersey trap but not by CO2-baited Centers for Disease Control and Prevention light trap. Aedes japonicus were collected from each of the 7 counties surveyed; in 5 of the counties for the 1st time in 2009. Preliminary findings suggest that a control strategy involving intensive source reduction can reduce Ae. japonicus populations. PMID- 21033062 TI - Comparison of engorged Culex quinquefasciatus collection and blood-feeding pattern among four mosquito collection methods in Puerto Barrios, Guatemala, 2007. AB - Investigators have used a variety of techniques to sample resting, engorged mosquitoes for the purposes of studying mosquito blood-feeding behavior. However, evidence exists that mosquito blood-feeding patterns may vary according to collection method. Engorged mosquitoes were collected from rural and urban habitats after the 2007 dry (July) and wet (December) seasons in the Department of Izabal, Guatemala, with the use of Centers for Disease Control and Prevention (CDC) light traps, gravid traps, and aspiration from plastic pots and vegetation. We evaluated the utility of plastic pots as sampling tools for engorged Culex mosquitoes and compared Cx. quinquefasciatus blood host identities among collection methods. The array of vertebrate hosts supplying blood to Cx. quinquefasciatus did not differ significantly by method of collection. The density of engorged Cx. quinquefasciatus per trap-night was not significantly different between CDC light traps, gravid traps, and plastic pots; however, there was a significantly higher proportion of total mosquitoes that were engorged collected from pots than from either CDC light traps or gravid traps. PMID- 21033063 TI - Population dynamics of Lutzomyia shannoni (Diptera: Psychodidae) at the Patuxent National Wildlife Research Refuge, Maryland. AB - The seasonal abundance and temporal patterns of the adult sand fly (Lutzomyia shannoni Dyar) were examined at the Patuxent National Wildlife Research Refuge, MD, from August 3, 2005, to July 29, 2006. A total of 138 (53 males, 85 females) L. shannoni was collected from 4 dry ice-baited traps set at the same 4 locations throughout the study. The male:female ratio was 1:2.4. All 4 traps, separated by a maximum distance of approximately 1.6 km, operated simultaneously on the collection dates. The collection dates were spaced apart by near weekly intervals during the months of expected sand fly activity. No collections occurred in December-February. August was clearly the period of peak adult abundance as the numbers collected were significantly greater during this month than any other month of collection. Results indicate the existence of a unimodal pattern of abundance with adult emergence beginning in June and ending by September. The temporal pattern and abundance differ from what has been observed for the species on Ossabaw Island, a barrier island located along coastal Georgia, and at San Felasco Hammock Preserve State Park, Gainesville, FL. Continued research is needed to compile multiyear data to confirm the temporal abundance patterns of this species in Maryland. PMID- 21033064 TI - Aqueous 2% geraniol as a mosquito repellent failed against Aedes aegypti on ponies. AB - Organic insect repellents are of interest to many agricultural producers and animal owners. Geraniol, a plant-derived alcohol, is naturally produced by a wide range of plants and is a US Environmental Protection Agency minimum risk pesticide. Previous studies have shown various concentrations of geraniol repel or kill mosquitoes; however, geraniol might cause allergic contact dermatitis in humans or animals. We tested a commercially available 2% aqueous solution of geraniol on ponies as a mosquito repellent. Five trials were conducted on ponies treated with a 60-ml aerosol mist (30 ml per side) of 2% geraniol or as untreated controls. Animals were observed 3 h postapplication to check for skin irritation. Aedes aegypti, in feeding tubes, were held on the ponies for 7 min. The average percent of biting on control animals was 56%, with a range of 16-90%, and the average for the treatments was 13%, with a range of 0-86%. Based on statistical models, there was no significant difference (P = 0.081) in the percent bites between treated and untreated animals after 3 h. Based on our data, 2% geraniol was not an adequate mosquito repellent for horses. We did not observe any skin irritation on the animals treated with 2% geraniol. PMID- 21033065 TI - A novel device to test the movement of a larvicide. AB - A larval holding chamber was designed to evaluate the movement of a new formulation of a mosquito larvicide. The chamber confines the mosquito larvae to a specific area and allows the larvicide to travel to them. After a 30-h test period, the larvicide being tested had killed all the larvae in the experimental chambers, whereas larvae confined in control chambers were not affected. The larval holding chamber is a good option for testing the movement of a larvicide through water. PMID- 21033066 TI - Evaluation of lurex 3, octenol, and CO2 sachet as baits in Mosquito Magnet Pro traps against floodwater mosquitoes. AB - Field evaluation of Lurex 3, 1-octen-3-ol (octenol), and CO2 sachet as baits in Mosquito Magnet Pro traps (MMP) for collecting adult mosquitoes was conducted at 2 different locations in northeast Florida. A total of 18 species of mosquitoes were collected by the MMP baited with the 3 attractant baits in St. Augustine, FL. The MMP baited with octenol collected significantly more mosquitoes than the traps baited with Lurex 3 and the CO2 sachet. A total of 6 floodwater mosquito species were collected by the MMP baited with the 3 attractant baits in Elkton, FL. The MMP baited with Lurex 3 or octenol collected more mosquitoes than the MMP baited with CO2 sachet or MMP alone. PMID- 21033067 TI - Evaluation of lambda-cyhalothrin barrier spray on vegetation for control of Aedes albopictus in China. AB - Aedes albopictus is a primary nuisance pest and disease vector in China. Control of Ae. albopictus using current methods is difficult because of diverse larval breeding sites. In the present study, lambda-cyhalothrin was applied as a barrier spray to vegetation surrounding human dwellings for control of adult mosquito populations. Compared to the landing rate counts in the untreated control site, the barrier spray resulted in an 83-98% reduction of Ae. albopictus within 9 wk posttreatment. The study results indicate that lambda-cyhalothrin applied as a barrier spray to vegetation can reduce Ae. albopictus landing rates collections for more than 2 months. PMID- 21033068 TI - Public health pesticide use in California: a comparative summary. AB - California pesticide use summary data and use reports from local vector control agencies were reviewed to document public health pesticide use patterns. During the 15-year period 1993-2007, public health pesticide use averaged 1.75 million lb (0.79 million kg) (AI), accounted for < 1% of reportable pesticide use statewide, and ranked below major crop uses and many nonagricultural uses. A review of reports from local vector control agencies (2004-07) indicated that their applications were principally for mosquito control and represented > 99% of all reported public health pesticide use. Petroleum distillates, principally larviciding oils, accounted for 88% of public health pesticide use. Pyrethrins and naled, used as mosquito adulticides, increased substantially in recent years (post-2004), coinciding with increased West Nile virus control activities and availability of emergency funding. PMID- 21033069 TI - Health tips. First aid kits. PMID- 21033070 TI - New treatment option for Dupuytren's contracture. PMID- 21033071 TI - Scrotal lumps and swelling. In older men, usually not cancer. PMID- 21033072 TI - Pain 'red flags'. Recognizing the signs. PMID- 21033073 TI - My doctor drained a sebaceous cyst that was on my neck. Now, my doctor is suggesting that I also consider having it surgically removed. Why? PMID- 21033074 TI - Drivers of innovation in pediatric nutrition. Preface. PMID- 21033075 TI - [Tobacco use among women in low- and middle income countries]. PMID- 21033076 TI - [Evolution of metabolic syndrome]. PMID- 21033077 TI - [Correlation of metabolic syndrome clinical signs and genetic determinants at children with obese]. AB - The aim of the work was to study the clinical and genetic factors at children with obese that predispose to the development of MS, and the development of algorithm for generating risk of MS. MATERIALS AND METHODS: Two comparable age and sex groups of children--148 children with obesity and 46--with normal body weight. We assessed anthropometric indices, blood pressure (BP), lipid profile, carbohydrate metabolism, the level of uric acid. 83 children with obesity were genotyped for polymorphisms: I/D gene ACE, G-75A ApoA1, S19W ApoA5, Sstl ApoC3, E2/E3/E4 ApoE and W/R ADRB3. RESULTS: 98,0% of children had abdominal obesity. In 35,8% was identified high blood pressure. In 47,4% was diagnosed hypo-alpha cholesterolemia and/or hypertriglyceridemia (HTG). In 21,0% of children was identified hyperglycemia. 25,7%were suffered from hyperuricemia. Among the genotyped children 57,0% of homo-and heterozygous carriers of D allele ACE gene had high blood pressure. More than half of the holders of 19W-allele ApoA5 (68,5%),--75A-allele of ApoA1 (56,0%), 52-allele of the gene ApoC3 (53,0%), E4 ApoE gene (85,7%), in the heterozygous state had metabolic TG and/or HDL. In 60,3% of the carriers W/W genotype of ADRB3 gene revealed a combination of hyperglycemia with hyperinsulinemia and/or TG. CONCLUSION: As a result of, aiming aimed at early detection of the major manifestations of MS clinical and genetic study was revealed stable combination of constitutional, metabolic and molecular genetic factors. Based on these data was developed algorithm for forming groups at risk of MS and individual tactics to prevent and/or therapy. PMID- 21033078 TI - [The role of hormones and types of food behavior in the development of metabolic syndrome]. AB - THE AIM: To investigate the role of hormones and the types of FB in the development of morbid obesity (MO), to develop a treatment policy for MO to examine the diagnostic predictive value of the FB hormones and FB modifications. MATERIALS AND METHODS: Were investigated 67 patients: 28 (42%) males and 39 (58%) female aged 18 to 60 years under the scheme: medical history, questionnaire on the questionnaire SF-36, score types of FB, the study of the anthropometric data (OT/OB, BMI), the definition of the FB hormones with subsequent control of BMI, OT/OB dynamics, types and FB hormones. RESULTS: In patients older than 50 years were dominated abdominal FB, in patients younger than 50 years - all three types of FB in approximately equal proportions. After the decline in MT was observed pattern between the FB modification and age of the patient. There was an increase of leptin and ghrelin and decrease in serotonin at all three types of FB. After weight correction was a decreased leptin, ghrelin, and increased serotonin, but the achievement of normal numbers are not marked. The paradoxical result is related to a violation of reciprocal relations of hormones. CONCLUSIONS: In patients with MO FB hormone levels (Leptin, Ghrelin) elevated to normal values, reduced levels of serotonin, there is an infringement of their reciprocal correlations. The approach to patients should be lengthy and complex, involving multidisciplinary team aimed at FB correcting the with the rejection of improper food stereotype. In the treatment of MO must used different methods: reducing diet, physiotherapy effects, drug therapy and their combination with the selection of individual programs, taking into contraindications account. For the above techniques inefficiency is necessary to use surgical treatment. Correction of FB in patients older than 50 years is the most difficult task (due to the presence of concomitant diseases). Necessary to draw attention and to start treatment at a young age. PMID- 21033079 TI - [Non-alcoholic fatty liver disease as an atherosclerosis risk factor]. AB - Currently, along with cardiovascular disease, changes in lipid and carbohydrate metabolism in the syndrome of insulin resistance seen pathology of the liver. The aim of our study was to determine the prognostic significance of nonalcoholic fatty liver disease (NAFLD) to assess the risk of early manifestations of atherosclerotic disease of carotid arteries. The correlation between the presence of NAFLD and signs of early atherosclerosis in the insulin resistance syndrome. The resulting ranked a number of prognostic factors influencing the degree of change in the walls of the carotid arteries, making it possible to construct estimates of individual risk of atherosclerosis development in clinically healthy patients. The clinical significance of the results is the need for more thorough examination of patients with NAFLD to assess risk factors for progression of pathology not only the liver, and cardiovascular disease. PMID- 21033080 TI - [Hypolipidemic therapy in patients with non-alcoholic fatty liver disease]. AB - To date generally accepted that one of the major risk factors for cardiovascular disease (CVD) and atherosclerosis is dyslipidemia. The undoubted fact is that the liver plays an important role in the development of atherogenic dyslipidemia, and simultaneously being the target organs, which leads to the development of nonalcoholic fatty liver disease (NAFLD). NAFLD is a major risk factor for CVD, it limits the possibilities for adequate lipid-lowering therapy, increasing cardiovascular risk. In this regard, the treatment of atherogenic dyslipidemia with statins and fibrates appropriate to hepatoprotectors disposal. Hepatoprotectors choice depends on the stage of NAFLD. At the steatosis stage of the NAFLD expedient method of statins in combination with essential phospholipids. At the nonalcoholic steatohepatitis (NASH) stage of NAFLD patient should receive statin therapy combined with ursodeoxycholic acid (UDCA). Patients with high levels of hypercholesterolemia in achieving target levels of cholesterol--low lipoprotein density (LDL-cholesterol) and decrease the side effects is the best combination of statins with the cholesterol absorption inhibitor. The complex lipid-lowering therapy in patients with NAFLD should include drugs that normalize the intestinal microflora (intestinal antiseptic, pre- and probiotics). PMID- 21033081 TI - [Diagnostic value of nitric oxide and endotoxins at non-alcoholic fatty liver disease]. AB - The aim of this examination was investigation of the nitrogen oxide (NO) role for the inflammation forming in the patients with nonalcoholic fat disease of the liver. 90 patients (male--25, women--65) were examined: steatohepatitis (SH)--60 patients, liver steatosis--30 patients). Index of body mass was increased on 40 45%. NO metabolites blood level was examined by Metelskaya V.A. (2005) method. The trustworthy increase of NO production in the SH patients in comparison in patients with steatosis liver and was increasing together with aminotransferases and GGTP. NO as inflammation marker may be real criterion of the liver inflammation in the patients with the early stage transformation of liver steatosis to SH. PMID- 21033082 TI - [Taurine in the treatment of non-alcoholic fatty liver disease]. AB - Non-alcoholic fatty liver disease (NAFLD) has several phases of flow: from simple steatosis, steatohepatitis, and ending with fibrosis and cirrhosis. NAFLD characterized by elevated liver enzymes in blood serum, the morphological changes in biopsies of the liver often associated with metabolic disorders. Metabolic syndrome represents a complex of many linked to pathobiochemical and pathophysiological factors levels influencing the extremely high risk of developing coronary heart disease (CHD), diabetes mellitus type 2 and other diseases associated with atherosclerosis. NAFLD proceeds favorably without significant morphological changes in most of the patients. In connection with this treatment is given only to patients with high risk of progression of this disease or the presence of marked changes in biochemical liver tests. Therefore, prevention and treatment of these conditions should be conducted before the complications and lead to improvement of the liver. PMID- 21033083 TI - [Interval hypoxic-hyperoxic training in the treatment of the metabolic syndrome]. AB - AIM: to investigate the possibility of a new method--interval hypo-hyperoxic training (IHHT)--in the correction of the individual components of metabolic syndrome. MATERIALS AND METHODS: The study included 35 patients with metabolic syndrome (alimentary obesity 1-3rd stage [BMI over 30 kg/m2], violation of carbohydrate tolerance or diabetes mellitus type II, hypertension and dyslipidemia). All patients were random separated into three groups: control (11 pers., basic therapy), trial 1 (13 pers. who have undergone 12 procedures of the IHHT) and trial 2 (11 pers. who have undergone IHHT in parallel with systemic hyperthermia and vibrating massage hardware). Course duration was 21 days average. Prior to the course procedures IHHT and the 3-day 4 upon completion all patients were fully examined. This examination included history taking, assessment of diet, psychometric testing, counseling psychologist to determine the type of feeding behavior, anthropometric measurements; body impendansemetria, biochemical study of blood determining the level of total cholesterol, HDL, LDL, TG, fasting plasma glucose (GP), 6-minute walk test to assess physical performance. Was established that the use of hypo-hyperoxic exercise (alone or in combination with systemic hyperthermia and hardware vibratory) leads to a significant reduction in body weight. It mainly arise by reducing fat mass accompanied by a reduction of total cholesterol, LDL, GPN, optimization of blood pressure, increased hypoxic stability, physical endurance, improved mental status. At individual selection of the course structure, dosing of hypoxic effects, combined with other physiotherapy method has some promise in treatment and rehabilitation of patients with metabolic syndrome. PMID- 21033084 TI - [Hypolipidemic effect of honey, pollen and pergam at patients with atherogenic dyslipidemia]. PMID- 21033085 TI - [Experimental steatosis of the pancreas]. AB - The article deals with steatosis of the pancreas in experimental metabolic syndrome. The possibility of modeling of the metabolic syndrome in rats with the development of liver steatosis and steatosis of the pancreas is demonstrated. Morphological changes in insular apparatus are similar to those with metabolic syndrome in the clinic. PMID- 21033086 TI - [Surgical hospital endotoxicosis as a problem of clinical gastroenterology]. AB - The original conception of "surgecal endotoxicosis" is presentation in the artical. MATERIALS AND RESEARCH METHODS: 2064 of a patients and results of 320 autopsies was divided into 4 groups in depending with bowel dysfunctions. There is the new classification of surgecal endotoxicosis in this article. Also the authors propose some technologies of detoxication. PMID- 21033087 TI - [Obesity in childhood]. AB - In this article presented modern data on the definition of obesity in childhood and its prevalence. Were reflected the basic diagnostic criteria for obesity and metabolic syndrome. Were analyzed genetic changes, hormonal factors, influence lifestyle of modern man as the reasons of the obesity. Are also was considered data on the relation of obesity and its complications such as cardiovascular, metabolic syndromes, nonalcoholic fatty liver disease. Was reflected the views of various specialists (cardiologists, endocrinologists, gastroenterologists, pediatricians) to the problem of overweight and obesity in children and adolescents. Were presented modern data on the approaches to the treatment of obesity in children. PMID- 21033088 TI - [Metabolic syndrome: a pediatrician view]. AB - The review of literature considers the problem of metabolic syndrome in pediatric practice. The review discusses pathogenesis of metabolic syndrome and diagnosis for the children. A therapeutic algorithm and an approach to the principles of diet the therapy is presented. PMID- 21033089 TI - [Thyroid dysfunction and soft fatty liver disease]. AB - This review discusses the correlation of thyroid dysfunction and non-alcoholic fatty liver disease. PMID- 21033090 TI - [Effectiveness of the new plant hepatoprotector--Ropren in patients with non alcoholic steatohepatitis]. AB - Liver damage causes serious metabolic disorders, immune response, detoxification functions and antimicrobial protection. Therefore, the problem of finding new high effective drugs for the restoration and normalization of liver function is extremely urgent. This article presents a new domestic plant hepatoprotector Ropren, which is a biopolymer polyprenols isolated from the green of pine and spruce, and an analog of the endogenous lipid--dolichol. Presented the Ropren efficiency in patients with nonalcoholic steatohepatitis. The drug reduces the clinical and biochemical disease activity, contributes to the normalization of lipid profile. The resulting decrease in the index treatment of fibrosis, determined by indirect transient elastometry, indicates an increase in the elasticity of the liver and reducing the risk of developing cirrhosis. PMID- 21033091 TI - [Use of Saccharomyces boulardii in treating patients inflammatory bowel diseases (clinical trial)]. AB - The aim of the clinical research was to study the efficacy of Saccharomyces boulardii in treatment of patients with Inflammatory Bowel Diseases. Results of investigation demonstrate more rapid regression of intestinal dyspepsia symptoms, decreasing clinical activity of IBD and improvement of intestinal microbiota composition in IBD patients have been treated by Saccharomyces boulardii. Lyophilized Saccharomyces boulardii are compatible with medical agents of the standard IBD therapy and have high level of safety. PMID- 21033092 TI - [Lanzoptol efficacy at gastroesophageal reflux disease: results of multicenter study leader]. AB - Results of multicenter study "Efficacy of Lansoptol (lansoprazole, KRKA) and its influence on the Dynamics of GERD symptoms" (LIEDER) are presented. The impact of 56-days treatment with lansoprazole 30 mg once daily on symptoms relief, a quality of life of 121 patients with gastroesophageal reflux disease (GERD) and healing of esophageal lesions of 30 patients with reflux esophagitis were investigated. Rapid acid inhibition effect of first dose of lansoptol was shown by 48-hr pH-monitoring. At the first day of the treatment 43.1% of patients reported decreasing of intensity of heartburn and 36.5%--of regurgitation. It were shown that the treatment with lansoptol provided symptoms relief in 25% patients at day 3, in 50% of patients at day 5 and in 75% at day 8 for heartburn, and at days 2, 6 and 9--for regurgitation. It was conducted improvement of quality of life. Healing rate of esophagitis at 28 day was 83.3%. PMID- 21033093 TI - [Recurrent hernia of the esophageal diaphragm heatus at patients with postoperative ventral hernia (some features of surgical tactics)]. AB - A clinical observation of patients with recurrent hernia of the esophageal diaphragm heatus and postoperative ventral hernia. We described some features of surgical treatment, the need to perform simultaneous operations. PMID- 21033094 TI - [Obesity and metabolic syndrome in children and adolescents (outpatient study results in Moscow)]. PMID- 21033095 TI - [Differential diagnosis of liver focal formations at diffusion MRI]. AB - PURPOSE: To define the role of diffusion-weighted imaging and MRI contrast enchanced in the differential diagnostics of focal liver lesions. METHODS AND MATERIALS: Forty patients with focal liver lesions (23 metastases, 32 cysts, 24 hemangiomas) underwent MRI at 1.5 T scanner. The protocol included T1, T2 imaging, DWI. For DWI we used b = 50, 400 s/mm2. Coefficient of signal intensity (kSI) for different sequences was counted by the formula: kSI = (SIa-SIb)/(SIa + SIb), where SIa was the lesion signal intensity, SIb was SI of normal liver parenchyma. RESULTS: Metastases had maximal kSI of DWI with b = 400 (kSI = 0.44 U) and minimal signal intensity of T1-WI (kSI = 0,29 U). On T1-W images the cysts differed greatly from liver parenchyma and from other focal lesions (kSI = 0,37 U), but hemangiomas hardly differed from metastases on this sequence (kSI, for these lesions was equal, 0.14 U). Using DWI made the differential diagnosis of different liver lesions easier because their kSI were significantly different: kSI for cysts was 0.68 U, kSI of hemangiomas was 0.61 U, kSI of metastases was 0,30 U. We need more studies for define the role of MRI contrast enchanced in the differential diagnostics of focal liver lesions. CONCLUSION: DWI plays an important role in differential diagnostics of focal liver lesions and should be included in protocol of examination of patients with liver pathology. PMID- 21033096 TI - [Surface tractotomy of trigeminal nerve sensory root:a new tractotomy for the treatment of trigeminal neuralgia]. AB - OBJECTIVE: To evaluate the feasibility of surface tractotomy of trigeminal nerve sensory root (STS) for the treatment of trigeminal neuralgia (TN). METHOD: Seven patients with TN were operated on using the STS. The six patients were followed up for 4.8-9.8 years. The trigeminal nerve root (TNR) obtained from 30 cadavers were performed microanatomical research using paraffin embedding and hematoxylin eosin staining technique. RESULT: Clinically, the patients' symptoms, such as face ache, disappeared after the surface nerve fiber bundles of trigeminal nerve sensory root (TNSR) were cut off. Only one patient died of brainstem bleeding on postoperative day 18. Histological examination: The common type of sensory root fibers were arranged parallel for 3-6 mm at its exit of brainstem, and then the glial myelin transformed to Schwann cells. The axon bifurcated from outer layer to middle region, and gradually formed the tiny nerve fiber bundles in the surface layer and the giant nerve fiber bundles in the center of the root. CONCLUSION: TN can be radical cured by STS without lesioning of nerve functions. Therefore,this new approach is an effective, advanced surgical technique for TN treatment. PMID- 21033097 TI - [Evaluation of infant hearing loss with high-risk factors after failed hearing screening]. AB - OBJECTIVE: To evaluate the characters and hearing changes of the infants failed in hearing screening with high-risk factors for hearing loss. METHOD: Two hundred and forty-four infants (488 ears) who failed in the hearing screening or with the different results between the first and second screening, were tested by auditory brainstem response (ABR), distortion product otoacoustic emissions (DPOAE) and acoustic immittance measurement in this study. RESULT: (1) A little proportion results among the three DPOAE screening was variable, the pass rate in the right ear was higher than that in the left-ear. (2) Forty-five of 184 ears which had passed the third DPOAE evaluation had the abnormal ABR results, the discrepancy rate between the two methods was 24.5% (45/184); 20 of 304 ears which failed in the hearing screening had a normal ABR results, with the discrepancy rate of 6.6% (20/304). (3) The highest proportion of abnormal result of the ABR in each groups was mild hearing loss, normal ABR in each groups also had a large proportion. The proportion of moderate hearing loss in the group of no more than three months old infants was significantly increased compared with the other two groups (P < 0.01), and no significant difference of severe hearing loss among the three groups (P > 0.05). (4) More than 70% of type A tympanogram was found in each groups (P > 0.05), the ratio of type B in moderately abnormal group was higher than other groups. Type C was only detected in one ear with severe hearing loss. (5) 29.5% infants had suffered the hyperbilirubinemia, which was much higher than the other risk factors (P < 0.05). CONCLUSION: The hearing loss of infants with high-risk factors are mostly mild, and show some indication of fluctuating. Some moderate hearing loss have the tendency to changes better. The combined use of electrophysiological measures can improve the accuracy of hearing evaluation. PMID- 21033098 TI - [An epidemiologic study of vertigo among middle school students in the city of Xiran]. AB - OBJECTIVE: To investigate the prevalence of vertigo and related risk factors in middle school students in the city of Xi'an. METHOD: A cross-section study was used to investigate on vertigo among middle school students. Questionnaire ,ear examination and auditory tests were carried out by the staff who received special training. Multiple Logistic regression models were used to analyze the relative influential factors about vertigo. RESULT: There were 1567 middle school students who underwent a complete investigation. The participants comprised 793 males (50.6%) and 774 females (49.4%). The overall prevalence of vertigo was 5.6%. No significant difference of the prevalence was found between males (4.7%) and females (6.5%) (P > 0.05). The use of MP3 or MP4, insomnia and history of middle ear infections or ototoxic drugs ingestion were the main risk factors for vertigo (odds ratio: 2.837, 5.582, 2.808 and 1.695, respectively). CONCLUSION: Vertigo has an influence on the study and living of the students. More researches are urgently needed on prevention and treatment of vertigo. PMID- 21033099 TI - [Vertigo due to neurovascular cross-compression: diagnosis and treatment]. AB - OBJECTIVE: To explore the clinical characteristics, pathological mechanism, diagnose, differential diagnosis and the treatment of vascular compressive vestibular neuropathy. METHOD: The authors retrospectively studied 2 cases of vascular compressive vestibular neuropathy about clinical characteristics, auditory tests, vestibular tests and imaging examine results, pharmacotherapy results and reviewed the related documents. RESULT: There were some common clinical characteristics: (1) Vertigo and disequilibrium could be elicited by any physical activity and head movement and abated with complete bed rest; (2) Symptoms and signs can't be improved by vestibular suppressant medications; (3) When taken Dix-Hallpike test, true vertigo or a spinning sensation appeared during head movement, when head skilled at any position,the symptoms disappeared; (4) The suffering lateral often showed high frequency sensorineural hearing loss ,the ABR of the suffering lateral showed prolonged inter wave latency of I-III wave; (5) Vestibular tests showed central lesion; (6) Occupying lesion can be ruled out by CT and MRI, MRI showed neurovascular compression of vestibular nerve; (7) Taking carbamazepine plus baclofen or only Tegretol orally can alleviate symptoms. A great deal of surgeries confirmed neurovascular compression of cranial nerve U as a disease entity, the offending artery mainly anterior inferior cerebellar artery. Microvascular decompression of cranial nerve VIII can successfully relieve vertigo. CONCLUSION: Neurovascular compression of cranial nerve VIII is a disease entity beyond question. It's major characters were vertigo and disequilibrium which elicited by any physical activity and head movement, magnetic resonance tomographic angiography can give valuable information for diagnosis and treatment. Microvascular decompression can effectively relieve vertigo. PMID- 21033100 TI - [Posttraumatic benign paroxysmal positional vertigo: analysis of 23 cases]. AB - OBJECTIVE: To compare the clinical presentation and outcome between patients with traumatic-BPPV (t-BPPV) and idiopathic-BBPV(i-BPPV). METHOD: The clinical records of 186 patients with posterior canal BPPV were reviewed retrospectively. All patients were diagnosed using the Dix-Hallpike test and treated with the canalith repositioning procedure. The outcome of patients with t-BPPV was compared with patients with i-BPPV. RESULT: Twenty-three of 186 patients with BPPV fulfilled the diagnostic criteria for t-BPPV. Women were affected i-BBPV more often than men (2.3:1), and women and men were equally affected t-BBPV (1:1). After one physical treatment, 34.8% of patients with t-BPPV had complete resolution of signs and symptoms in comparison to 85.3% of patients with i-BPPV (P < 0.05). During the 2-year follow-up, 56.5% of t-BPPV patients and 19.0% of i-BPPV patients had recurrent attacks (P < 0.05). CONCLUSION: The nature and severity of the traumas causing t-BPPV are diverse. It appears that t-BPPV is more difficult to treat than i-BPPV, and also has a greater tendency to recur. PMID- 21033101 TI - [Expression of PCNA, BCL-2, CD4+, CD8+ in the adenoid tissues from children with secretory otitis media]. AB - OBJECTIVE: To investigate the relationship between immune status of adenoids and secretory otitis media (SOM). METHOD: The adenoid tissue samples of 72 cases with SOM and 30 cases with adenoid hypertrophy without SOM were studied by immunohistochemical method. RESULT: The PCNA, BCL-2, CD4+, CD8+ and CD4+ / CD8+ in SOM tissue samples were 30.85 +/- 1.73, 21.27 +/- 1.25, 41.90 +/- 9.07, 20.45 +/- 7.08 and 2.10 +/- 0.17, respectively, which were much more than that of tissue samples without SOM (25.25 +/- 1.75, 14.05 +/- 1.02, 16.30 +/- 8.21, 11.15 +/- 5.71, 1.39 +/- 0.15 respectively) (P < 0.01). The expression of CD4+ in T lymphocyte was obviously higher than that of CD8+. CONCLUSION: In adenoid tissues of SOM patients, the activity of T-lymphocyte subsets are increased,the adenoids are enlarged and local immunity are enhanced. Therefore,adenoidectomy should be applied in SOM patients as early as possible. PMID- 21033102 TI - [Analysis on the relationship between tensor veli palatini and secretory otitis media in patients with nasopharyngeal carcinoma after radiotherapy]. AB - OBJECTIVE: The analyze the relationship between secretory otitis media (SOM) and injury of tensor veli palatini (TVP) muscle injury after radiotherapy, then to explore the pathogenesis of SOM in patients with nasopharyngeal carcinoma (NPC) after radiotherapy. METHOD: The cross section area (CSA) of TVP and medial pterygoid (MP) muscle were measured in MRI of 32 patients with NPC before and after radiotherapy, meanwhile the incidence of SOM were surveyed after radiotherapy, then to analyze the relationship between the change of TVP and the incidence of SOM after radiotherapy. RESULT: Of 48 ears without SOM before radiotherapy, 27 ears developed post-irradiation SOM, including 24 ears with TVP atrophy and 3 ears without TVP atrophy, and 21 ears had no post-irradiation SOM, including 8 ears with TVP atrophy and 13 ears without TVP atrophy. chi2 test showed significant difference (P < 0.01). It indicated that post-irradiation SOM have correlation with TVP atrophy. The more possibility of TVP atrophy occurred after long time radiotherapy. CONCLUSION: The atrophy of TVP in patients with NPC usually occurs 6 months after radiotherapy, and this may result in the post irradiation SOM. The pathogenesis of post-irradiation SOM need further study functionally. PMID- 21033103 TI - [Compare of CT scan of the nasopharynx in patients with obstructive sleep apnea hypopnea syndrome and health]. AB - OBJECTIVE: To explore the impact of nasopharynx and palatum durum on the pathogenesis and severity of OSAHS patients via CT scan, and to establish a foundation to select the suitable surgical procedures. METHOD: Thirty nine OSAHS patients diagnosed by PSG and 30 normal adults were included in this study. Successive CT scanning were undertaken from roof of nasopharynx to glottis and then the CT scan slices were reconstructed in sagittal plane through Efilm software. The parameters were measured in the midline of the nasopharynx,the longest section of the hard palate and then were analyzed by t test. RESULT: The subspinale-posterior nasal spine (A-PNS) of OSAHS patients were longer than those of normal adults. The posterior nasal spine-culminating point of nasopharynx (PNS R) and posterior space of hard palate (PNS-B) of OSAHS patients were less than those of normal adults. A 95% confidence interval were calculated from the parameters of 30 normal adults. Among 39 OSAHS patients, the A-PNS in 6 patients were longer than the top limit of normal,the PNS-R in 10 patients and the PNS-B in 16 patients were less than the low limit of normal adults, 2 patients were seen the differences of both A-PNS and PNS, 5 were seen the differences of both PNS-R and PNS-B, and 1 were seen the differences of A-PNS and PNS-B. The AHI of 24 OSAHS patients with smaller nasopharynx and longer hard palate were larger than that of the other 15 OSAHS patients, meanwhile the SaO2 of the former patients were lower than the latter. CONCLUSION: Though the narrow of the upper airway in OSAHS patients mainly attribute to the nasopharynx, the nasopharyngeal size and the length of hard palate are also involved in the pathogenesis and severity of OSAHS and should be considered when choosing the surgical procedures. PMID- 21033104 TI - [Autoradiography observation on cochlea and organs in guinea pigs after intra abdominal injection of bFGF]. AB - OBJECTIVE: To observe whether bFGF could cross the blood-labyrinth barrier (BLB) after intra-abdominal injection and to establish an experimental basis for its clinical applications. METHOD: Thirty guinea pigs were divided into three groups. Animals in group 1 were administered o I-bFGF, while animals in group 2 and 3 were administered 125 and saline, respectively, via intra-abdominal injection. The both cochlea, blood, liver, brain, thyroid gland and kidney were collected and weighted. A radioimmunoassay analyzer was employed to measure counts per minute (CPM) of each sample, and autoradiography was performed on both cochlea. RESULT: The CPM value of organ samples in the 125I group was higher than that in other groups, and radioactive grain was observed in cochlear samples of this group. In the 125I-bFGF group, blood demonstrated the highest CPM value, while cochlea and brain demonstrated the lowest CPM value, with no radioactive grain observed in cochlear samples. CONCLUSION: bFGF has some difficulties in getting across BLB, so the way of bFGF application in clinics need further study. PMID- 21033105 TI - [Simulating experimental study on ultrasonic elastography based monitoring of cryosurgery]. AB - Noticing the phenomenon that biological tissues will change its elasticity by orders of magnitude after it was frozen, we proposed in principle the strategy of using ultrasound elastography to monitor the formation and thawing of the iceball when performing a cryosurgery. Following our former theoretical evaluation, conceptual experiments were designed to apply ultrasound elastography to monitor three kinds of testing samples which includes: phantom embedded with glass block, phantom with tissues at normal temperature and phantom with frozen tissues inside. It was demonstrated for the first time that the ultrasound elastography could provide a high contrast picture on the ice ball during cryosurgery. The measurement errors involved in the application of the method was preliminarily analyzed and approaches to further improve the method were pointed out. With a much different value in elastography than that of water, monitoring the ice ball, the imaging target in clinics, is expected to be an important area for the application of ultrasound elastography. PMID- 21033106 TI - [The reconstruction study of EEG signal based on sparse approximation & compressive sensing]. AB - OBJECTIVE: Due to random sampling of non-adaptive, high-quality reconstruction of the original signal, one-dimensional non-stationary multi-channel EEG signal can be achieved automatic detection and analysis. METHODS: A new multicomponent redundant dictionaries with the atoms of the Gaussian function and its first and second derivatives was built in the paper, and reconstructed signal base on compressed sensing measurement model. RESULTS: The selected dictionary atoms can more effectively match the EEG signals in a variety of transient characteristics of the waveform, allowing the formation of EEG signal is more sparse matching pursuit decomposition. With the theory based on compressed sensing signal sampling, only half of the original signal with different sample size can be used to reconstruct the original signal quality, the important instantaneous features of the waveform can well be maintained. CONCLUSION: Signal sampling based on the theory of compressed sensing contains enough information of the original signal, using the prior conditions of EEG signals (or compressibility) sparsity, high dimensional signal and original image can be reconstructed through a certain decoding of linear or nonlinear model. PMID- 21033107 TI - [Quantitative analysis of electroencephalograph in depression based on phase synchronization]. AB - EEG signals of depression patients and normal control subjects under the states of closed eyes and mental arithmetic are investigated through the method of phase synchronization (PS) analysis. Compared with conventional quantitative EEG (qEEG) analysis, PS analysis is a powerful method which can detect the weak interaction between signals by quantifying the relationship of the instantaneous phases of the signals but excluding the influence of the amplitudes. Results suggest that the global PS index of depression in the two states are much lower than that of controls, and the left hemispheric and the inter-hemispheric PS indices of depression show significant difference from that of controls, while the right hemispheric PS index shows no significant difference between these two groups. PMID- 21033108 TI - [Study of the beam field of a new array ultrasound transducer]. AB - This paper provides a new design of 12-element array ultrasound transducer. By modeling the beam field model of single element and array and comparing simulated and real ultrasound beam field test data, it can be demonstrated that 12-element array ultrasound transducer has a much better field performance than the 8 element transducer. PMID- 21033109 TI - [Development and application of the phased HIFU system software]. AB - This paper introduces HIFU system software based on a phased-array HIFU device. Combined with the database and computer graphics technology, this HIFU system software can be used to develop the therapy planning semi-automatically, implement the pilot project efficiently and accelerate the clinical studies. PMID- 21033110 TI - [Comparison of endmember extraction at spectral unmixing for biological fluorescence imaging]. AB - We applied two classical algorithms in hyperspectral imaging to extract endmember for biological fluorescence imaging. A combined algorithm was found to initialize the PPI with decreasing the number of multi-spectral pixels, with subsequent N FINDR refinement, which could make a better result. PMID- 21033111 TI - [Study and compare of the bidirectional filtering technique for anti-baseline drift]. AB - Several digital filtering techniques for correcting baseline drift from ECG signals are presented. A bidirectional filter is introduced, which can cantain baseline drift their filtering performance and realization methods are compared. PMID- 21033112 TI - [Development and research of animal experimental cabin with ATM/LP and low oxygen and high carbon dioxide]. AB - This paper developed an experimental animal cabin with ATM/LP and low oxygen and high carbon dioxide. It is based on the unitized design of modern transmission technology, industrial measurement modules and configuration software. The cabin successfully simulated an enclosed environment of low oxygen and high carbon dioxide at constant pressure, automatically measured and controlled the concentrations of oxygen and carbon dioxide as well as temperature and humidity in the cabin for the first time. The system provided a technology platform for the equipment supporting clinical COPD study. The result is accurate, stable and reliable and can realize automatic measurement and control of cross. The clinical applications show that the cabin with accurate measurement and control is practical and reliable. PMID- 21033113 TI - [Research and development of the wireless network system to monitor clinical nursing information]. AB - OBJECTIVE: Independently research and develop the wireless network system to monitor clinical nursing information in order to meet the needs of clinical care. METHODS: The system consists of two sections which are the bedside machines and the central station. Advanced wireless network communications, microelectronics and computer technology are applied to continuously monitor various indicators of patients in intensive case units and general wards. Then the information was sent to the central monitoring station, which can automatically classify the data. RESULTS: The system includes 4 subsystems which are automatic monitoring of urine output, automatic monitoring of infusion, automatic measurement of patient body weight and automatic management device of postoperative drainage tubes, which can provide essential indicators for major surgeries and critical patients. CONCLUSION: The system has strong practicality. which can provide information for clinical care, ensuring the safety of medical care. PMID- 21033114 TI - [Development of a medical equipment support information system based on PDF portable document]. AB - OBJECTIVE: According to the organizational structure and management system of the hospital medical engineering support, integrate medical engineering support workflow to ensure the medical engineering data effectively, accurately and comprehensively collected and kept in electronic archives. METHODS: Analyse workflow of the medical, equipment support work and record all work processes by the portable electronic document. Using XML middleware technology and SQL Server database, complete process management, data calculation, submission, storage and other functions. RESULTS: The practical application shows that the medical equipment support information system optimizes the existing work process, standardized and digital, automatic and efficient orderly and controllable. CONCLUSIONS: The medical equipment support information system based on portable electronic document can effectively optimize and improve hospital medical engineering support work, improve performance, reduce costs, and provide full and accurate digital data PMID- 21033115 TI - [A waterproof equipment for endoscope equipment]. AB - The article introduces a new kind of waterproof equipment for endoscope. The equipment can resolve the problem that the endoscope's ocular and camera are always interfered by the Backstreaming liquid while performing surgical operation. The equipment is made up of three parts, which are ring-shaped locking structure, obturating ring and waterproof plastic sheath. Using the equipment can achieve the purpose of protecting the endoscope's ocular and camera effectively. PMID- 21033116 TI - [Design and implementation of medical instrument standard information retrieval system based on APS.NET]. AB - This paper Analys the design goals of Medical Instrumentation standard information retrieval system. Based on the B /S structure,we established a medical instrumentation standard retrieval system with ASP.NET C # programming language, IIS f Web server, SQL Server 2000 database, in the. NET environment. The paper also Introduces the system structure, retrieval system modules, system development environment and detailed design of the system. PMID- 21033117 TI - [Application and overview of image guided surgery system]. AB - This paper introduces the development and the key technology of image guided Surgery Systems (IGSS) and analyses its prospect in this paper. IGSS can be used in clinical surgery as an assistant tool, and it would be an advanced medical equipment combined with medical robotics. PMID- 21033118 TI - [Introduce the quality control of equipment of hemodialysis center]. AB - This paper introduces the quality control of equipment of hemodialysis center, which includes the wate of hemodialysis, disinfection of the equipment, maintenance, check and calibration of the equipment. PMID- 21033119 TI - [Detection of vaginal discharge by ultra-high power microscope and conventional microscope]. AB - OBJECT: To study the significance of the ultra-high power microscope in the examination of vaginal discharge. METHODS: By the ACT-2000 ultra-high power microscope system and Olympus CX21 microscope, the vaginal discharge of 1,100 gynaecology out-patients was examined respectively. RESULTS: The positive rate of mould in the patients was 11.55% by CX21 and was 20.27% by ACT-2000, respectively. The positive rate of trichomonas vaginalis was 2.55% by CX21 and 3.0% by ACT-2000, respectively. The clue cell was detected in 11.27% of the patients by ACT-2000, but no such cell reported by CX21. Totally, positive results were obtained in 14.09% of the patients by CX21 and 32.55% by ACT-2000. CONCLUSION: By using the ultra-high power microscope, the positive result can be increased obviously in the examination of vaginal discharge. It is very important in clinical practices. PMID- 21033120 TI - [Efficacy and safety evaluation of systemic red light therapy for burn wound repair]. AB - OBJECTIVE: To investigate effects of systemic red light therapy on wound repair of burned patients and discuss its possible mechanisms of wound healing promotion. METHODS: 138 burned patients were randomly divided into systemic red light treatment group (n = 69) and control group (n = 69). Patients in control group received routine therapy, while those in test group were given systemic red light therapy once a day, 30 minutes at a time until the wounds were recovered. The clinical findings and variables indicating wound repair were assessed on the 7th, 10th, 14th day, 21st day post-burn and the day when the wounds were healed. RESULTS: Mean time of wound recovery were 19.86 +/- 2.43 days and 21.02 +/- 2.97 days respectively of those deep-thickness wounds in test group and control group, with statistically significance (P < 0.05). For the severity of the pain, VAS during time of dressing change on the 10th, 14th day post burn was lower in test group than that in control group which indicated less painful in test group (P < 0.05), suggesting pain relief effect of systemic red light therapy. CONCLUSION: Systemic red light therapy was effective to promote wound healing of deep thickness burn wounds and other similar acute wounds. Simultaneously, it is efficacious in pain relief and safe for those patients. PMID- 21033121 TI - [Principle and application of orthopedic ESWT apparatus]. AB - The paper introduced the principle of extracorporeal shock wave therapy(ESWT) for orthopedics diseases including 60 cases of periarthritis of shoulder, 60 cases of tennis elbow and each compared with 60 control cases. The cure rate of ESWT for periarthritis of shoulder and tennis elbow is more than 93%, higher than the control group. PMID- 21033122 TI - [The management of the virtual secondary library for medical consumables and its systematic application and development]. AB - In order to improve of the flow control and flow supervision in the use of medical consumables, from administrative organizing to network management software designing, a scientific and rational approach to equipment use and management was explored which established the management mode of virtual secondary library for the medical equipment to achieve the combination of macro control and provision practice. PMID- 21033123 TI - [Research on the application of RAC technology in hospital information system]. AB - This paper presents a way to carry out the RAC technology in hospital, researches the key technologies of RAC, the result shows that performance of database is greatly improved by RAC technology. PMID- 21033124 TI - [Relationship between serum IL-8 hsCRP, TNF-alpha and coronary lesions in CHD patients]. AB - AIM: To study the relationship between serum inflammation factors interleukin-8 (IL-8), high-sensitivity C-reaction protein, tumor necrosis factor-alpha and coronary lesions in coronary heart disease (CHD) patients, METHODS: One hundred and six CHD patients were enrolled, 100 healthy subjects served as control group. The levels of serum IL-8, hsCRP (by) and TNF-alpha were determined. Coronary lesions were calculated by Gensini method. RESULTS: The levels of Serum IL-8, hsCRP and TNF-alpha in CHD group were significantly higher than those in control group were significantly higher than those in control group (P < 0.05), and serum IL-8, hsCRP and TNF-alpha in CHD group increased gradually with the increase of Gensini score (P < 0.05). Pearson correlation analysis showed that Gensini score was positively correlated to IL-8 (P < 0.05), hsCRP (P < 0.05) and TNF-alpha (P < 0.05) in CHD group. CONCLUSION: Severity of coronary lesions in CHD patients may be related to the levels of serum IL-8, hsCRP and TNF-alpha. PMID- 21033125 TI - [Role of interventional cardiologists in the management of acute ischemic stroke]. PMID- 21033126 TI - [Cost-utility analysis of percutaneous coronary intervention in 13 cities of China]. AB - OBJECTIVE: To investigate the cost-utility of percutaneous coronary intervention (PCI) in China. METHODS: A total of 630 patients from 13 cities undergoing PCI during the first half year of 2006 were enrolled in this study. The 36 items derived from the short form of health survey (SF-36) were applied prospectively in these patients before and 9 months after PCI. The cost per every incremental mark of SF-36 and quality adjusted life year (QALY) were calculated. RESULTS: (1) The age was lower than 60 years old in more than 50% patients. (2) In terms of detailed costs, material costs accounted for 82.5% of the hospitalization costs, medications costs accounted for 6. 8% , and operation fee accounted for 5.9%. These 3 items comprised 95.2% of overall hospitalization costs, and 69. 8% material costs were the cost for stents. (3)The average re-admission hospitalization costs were 17 841.5 RMB in 44 patients who were rehospitalized due to occurrence of major adverse cardiac events. (4) Follow-up made at months 1, 3, 6, 9, and 12 post index procedure showed that an average cost for postoperative drug treatment was 831.50 RMB per month, and most patients spent 400.0 RMB for drug treatment per month. (5) The average quality of life score increased by 20.59 post PCI (P < 0.05 vs. pre-PCI). The cost-effective analysis indicates that the cost per every incremental mark of SF-36 was 3975.7 RMB. The cost per every QALY gained was 59 898. 3 RMB. CONCLUSION: PCI is effective for patients with coronary heart disease and the cost per QALY in China was positioned in an acceptable range. PMID- 21033127 TI - [Association between post primary percutaneous coronary intervention myocardium reperfusion and prognosis in patients with acute ST-elevation myocardial infarction]. AB - OBJECTIVE: To explore the prognostic impact of post primary percutaneous coronary intervention (PCI) reperfusion status on outcome in patients with acute ST elevation myocardial infarction (STEMI). METHODS: A retrospective analysis was performed in 964 patients undergoing primary PCI for STEMI. Electrocardiogram and TIMI myocardial perfusion grade (TMPG) were analyzed by reader blinded to the clinical course. Patients were divided to four groups according to ST segment resolution (STR) and TMPG: group A were patients with good STR and TMPG(425/964), group B were patients with poor STR and good TMPG (239/964), group C were patients with good STR and poor TMPG (113/964) and group D were patients with poor STR and TMPG (113/964). RESULTS: Although TIMI grade III flow was achieved after mechanical reperfusion, abnormal reperfusion was still present in about 1/3 patients as shown by poor STR or TMPG. Older age, cardiac dysfunction and diabetes, prolonged time of pain to balloon/emergency room are independent risk factors for abnormal reperfusion post PCI. Major adverse cardiac events events in hospital (RR = 64. 63, P < 0.01) and during follow up (RR = 11.69, P < 0.01) were significantly higher in group D than in group A. CONCLUSION: Poor post PCI reperfusion status is associated with higher in hospital and during follow up major adverse cardiac events event in STEMI patients. PMID- 21033128 TI - [Electrophysiological characterization and efficacy of radiofrequency ablation of focal atrial tachycardia originating from the left atrial appendage]. AB - OBJECTIVE: To analyze the electrophysiological characteristics and efficacy of radiofrequency catheter ablation (RFA) of focal atrial tachycardia (AT) originating from the left atrial appendage (LAA). METHODS: Electrophysiologic study and RFA were performed in 9 patients (4 female) with focal AT originating from the LAA. Atrial appendage angiography was performed to identify the origin of AT. P waves were classified as negative, positive, isoelectric, or biphasic. RESULTS: The mean age was (21 +/- 9) years. AT occurred spontaneously or was induced by isoproterenol infusion rather than programmed extrastimulation and burst atrial pacing. A characteristic P-wave morphology and endocardial activation pattern were observed. Positive P-wave in inferior leads was seen in all patients, upright or biphasic (+/-) component P wave was observed in lead V1, isoelectric component or an upright component P wave with low amplitude ( < 0.1 mV) was seen in lead V2-V6. Earliest endocardial activity occurred at the distal coronary sinus (CS) in all patients. The earliest endocardial activation at the successful RFA site occurred (36.7 +/- 7.9) ms before the onset of P wave. RFA was successful in all 9 patients immediately post procedure. AT reoccurred in 2 patients within 1 month post RFA and AT disappeared post the 2nd-RFA. AT reoccurred in 1 patient and terminated after the 3rd RFA. At the final follow-up (12 +/ 5) months, all 9 patients were free of arrhythmias without antiarrhythmic drugs. CONCLUSIONS: The LAA is an uncommon site of origin for focal AT. The characteristic P wave and activation timing are suggestive for focal AT originating from the LAA. LAA focal ablation is safe and effective for patients with focal AT originating from the LAA. PMID- 21033130 TI - [Association of the tagging single nucleotide polymorphisms in transforming growth factor beta-1 gene with hypertension in the Han nationality population in Xinjiang]. AB - OBJECTIVE: Essential hypertension (EH) was a complex disease resulted from the interaction of cumulative effect of multiple genetic and environment factors. The relationship between the genetic polymorphisms in the transforming growth factor beta1 (TGF-beta1), the blood levels and EH have been investigated, but the conclusions were different. Therefore, we investigate the relationship between the tagging single nucleotide polymorphisms (tSNPs) (rs1800469, rs2241716, rs11466345, rs2241715, rs4803455) in TGF-beta1 gene, blood levels and EH in the Han nationality population in Xinjiang, to clarity the pattern of linkage disequilibrium (LD) and the feature of the structure of haplotype. METHODS: Based on the case-control study,we selected 732 (365 EH patients,367 controls) Han Chinese population from the Boertonggu countryside of Shawan region in the Xinjiang Uygur Autonomous Region of China by random cluster sampling. After questionnaire and physical examination, we collected blood samples, and the blood levels of TGF-beta1 were quantified using sandwich ELISA. The polymorphisms of TGF-beta1 gene in the study groups were detected with SNaPshot system. The case control study in a large group was carried out separately for each of the tSNP and followed up by haplotypes analyses to determine the relation between tSNPs of TGF-beta1 gene and EH in the Han population. RESULTS: (1) The frequencies of alleles A, G of rs11466345 of TGF-beta1 gene in EH group and control group were as follows: 69.7%, 30.3%, 74.4%, 25.6%, respectively. It was demonstrated that the G allele of the rs11466345 polymorphism occurred at a significantly higher frequency in EH patients than in healthy controls (30.3% vs. 25.6%, P < 0.05). The rs11466345G-allele carriers had a significantly increased risk of EH compared to rs11466345A-allele carrier (OR = 1.261; P < 0.05). The frequencies of genotypes and alleles of the other tSNPs of TGF-beta1 gene had no difference between EH patients and controls (P > 0.05). (2)Except the site of rs11466345, the other tSNPs were in strong LD, and no statistical differences were observed in haplotypes distribution in the followup study between case-control groups (P > 0.05). (3) There were no difference of TGF-beta1 levels between the different genotypes and alleles in tSNPs of TGF-beta1 gene (P > 0.05). CONCLUSIONS: (1) These results suggested that TGF-beta1 gene rs11466345 G allele was likely to be a genetic susceptibility factor for EH in the Xinjiang Han population, the other tSNPs perhaps had no association with EH of in the study groups. (2) Except rs11466345, the other tSNPs were in strong LD, and the haplotypes reconstructed by tSNPs might not be associated with EH in the Han nationality populations. (3) There was no association between the tSNP of TGF-beta1 gene and TGF-beta1 blood levels in the Xinjiang Han nationality population. PMID- 21033129 TI - [Virtual histology intravascular ultrasound assessment of coronary atherosclerotic plaques in diabetic patients]. AB - OBJECTIVE: To evaluate the components and characteristics of coronary atherosclerotic plaques in type 2 diabetic patients using virtual histology intravascular ultrasound (VH-IVUS). METHODS: In vivo atherosclerotic plaques (over 50% angiographic diameter stenosis) of the three main coronary arteries were analyzed by gray-scaled IVUS with planar and volumetric VH-IVUS in consecutive patients examined between September 2008 and March 2009. Patients were divided into two groups: diabetic mellitus (DM) group with 22 patients (39 lesions) and non-DM group with 46 patients (69 lesions). RESULTS: At the minimal lumen area (MLA) site, the percentage of NC (necrotic core) area (19.4% +/- 1.2% vs. 15.1% +/- 1.1%, P = 0.015) and dense calcium (DC) area (15.2% +/- 1.6% vs. 10.7% +/- 1.1%, P = 0.016) were significantly larger while fibrotic tissue (FT) area (56.7% +/- 2.3% vs. 64.8% +/- 1.8%, P = 0.007) was smaller in DM group than in non-DM group. Likewise, volumetric VH-IVUS analysis showed that the percentage of NC volume (21.3% +/- 1.3% vs. 16.5% +/- 1.1%, P = 0.008) and DC volume (16.6% +/- 1.4% vs. 11.3% +/- 1.1%, P = 0.003) were significantly larger while FT volume (55.1% +/- 2.1% vs. 63.9% +/- 1.8%, P = 0.003) was significantly smaller in DM group than in non-DM group. Moreover, significantly higher incidence of VH-TCFA (thin-cap fibro atheromas) was evidenced in the DM group than in the non-DM group (69.2% vs. 42.0%, P = 0.009). However, the remodeling index and the positive remodeling frequency were similar between the 2 groups. CONCLUSION: Incidence of necrotic core, dense calcium plaque and vulnerable plaques in stenotic lesions was higher in DM patients than in non-DM patients. PMID- 21033131 TI - [Serum neuropeptide Y level in hypertensive patients with obstructive sleep apnea syndrome]. AB - OBJECTIVE: To explore the potential role of neuropeptide Y (NPY) in the pathophysiological process of hypertension caused by obstructive sleep apnea syndrome (OSAS). METHODS: The concentration of serum NPY were measured with radioimmunoassay (RIA) in 417 subjects (97 normotensive controls without OSAS, 113 cases of normotensive with OSAS, 73 cases of hypertensive without OSAS and 134 cases of hypertensive with OSAS. Further, the mean NPY level were compared in four groups and the possible effective factors on NPY were discussed. RESULTS: (1) The concentration of NPY in four groups were (50.5 +/- 37.2) pmol/L in normal controls, (76.0 +/- 39.9) pmol/L in normotensive with OSAS group, (66.9 +/- 36.2) pmol/L in hypertensive without OSAS group and (86.8 +/- 36.8) pmol/L in hypertensive with OSAS group. Whether the patients with OSAS combined with hypertension or not, the concentration of NPY in the serum raised remarkably compared with those without OSAS and hypertension, the highest level of serum NPY was detected in OSAS combined with hypertension group. (2) Pearson correlation analysis indicated that both SBP and DBP related to the serum NPY significantly in non-OSAS group (AHI <10), while the BMI, abdominal circumference, AHI as well as the lowest level of SaO2 correlated to NPY besides SBP in OSAS group with (AHI > or =10). (3) Multiple linear regression model showed that the abdominal circumference and AHI were contributing factors to SBP, while neck circumference and BMI were contributing factors to DBP. The level of NPY in the serum were significantly affected by AHI and BMI, in which the former one had greater influence. CONCLUSION: The increased level of serum NPY may play weakly potential roles in the pathophysiological process of hypertension caused by OSAS. PMID- 21033132 TI - [Predictive value of human fatty acid binding protein for myocardial ischemia and injury in perioperative period of cardiac surgery]. AB - OBJECTIVE: To evaluate the value of human fatty acid binding protein (h-FABP) in predicting myocardial ischemia and injury in the perioperative period of cardiac surgery, we observed the dynamic changes of h-FABP in perioperative period of patients underwent coronary artery bypass grafting and ventricular septal defects repairing surgery, and evaluated the relationship of h-FABP and ischemia modified albumin (IMA), CK-MB, cTnI. METHODS: Patients underwent coronary artery bypass grafting (n=30) and ventricular septal defect repairing (n=30) surgery between February 2008 and December 2008 were included in this study. Venous blood sample was obtained at preoperative, aortic clamping, aortic unclamping of 10 min, 2 h, 6 h, 12 h, 24 h for the measurements of h-FABP, IMA, cTnI and CK-MB. RESULTS: h FABP and IMA changed in the same way at various examined time points, h-FABP changes also paralleled cTnI and CK-MB changes, h-FABP peaked early during myocardial ischemia and injury and returned to baseline level at 2 h post myocardial ischemia and injury. Linear correlation analysis showed that the peak value of h-FABP was positively correlated with IMA, CK-MB and cTnI in both CABG group (r = 0.948, 0.964 and 0.961, P < 0.05) and in the VSD group (r = 0.986, 0.978 and 0.957). CONCLUSIONS: h-FABP is an early diagnostic parameter reflecting perioperative myocardial ischemia and injury in cardiac surgery. Quantitative h FABP monitoring could predict the severity of myocardial ischemia and injury early during cardiac surgery. PMID- 21033133 TI - [Fibrinolytic therapy for femoral artery thrombosis after left cardiac catheterization in children]. AB - OBJECTIVE: The study was conducted to investigate the feasibility and effectiveness of fibrinolytic therapy for femoral artery thrombosis after left cardiac catheterization in children. METHODS: Thrombolytic therapy with urokinase was applied in 16 children (5 males) with femoral artery thrombosis after left cardiac catheterization. Patients were given a bolus injection of heparin, 100 U/kg. 30,000-100,000 U boluses of urokinase were injected intravenously, and then a continuous infusion of 10,000-50,000 U/h was started. Transcatheter thrombolysis was performed once previous procedures failed. RESULTS: All 16 patients presented lower limbs ischemia after left cardiac catheterizations. The age was (2.6 +/- 1.9) years, the height was (85.3 +/- 13.1) cm, the weight was (11.2 +/- 3.8) kg. Patients with cyanotic and acyanotic congenital heart disease were 2 and 14, respectively. Interventional therapy was performed in 12 patients. Absent arterial pulsations were found in 15 patients and reduced arterial pulsation in 1 patient. Femoral arterial perfusion became normal in all patients (3 after transcatheter thrombolysis, 11 post intravenous thrombolysis and 2 post intravenous heparin). The average doses of heparin and urokinase were (950 +/- 682) U and (295,357 +/- 198,770) U. The average duration of therapy was (7.25 +/- 5.31) h. Mild residual stenosis were found in 2 patients post various treatments. CONCLUSION: Fibrinolytic therapy with urokinase is a safe and useful modality for children with femoral artery thrombosis after left cardiac catheterization. PMID- 21033134 TI - [Anatomy variation of coronary vein system in patients with ischemic heart disease and non-ischemic]. AB - OBJECTIVE: The purpose of this study was to analyze the anatomy variation of coronary vein system in patients with ischemic heart disease (IHD) and non ischemic heart disease (NIHD). METHOD: Forty-one patients with IHD and 87 patients with NIHD [101 men, mean age (63.5 +/- 10.6) years] were included in this study. RESULTS: Coronary sinuses were successfully cannulated and venographies were obtained in 127 cases. Transvenous LV pacing leads were successfully placed in optimal coronary vein in 123 cases (96.09%). The majority (76.38%) patients had at least one or more vessel abnormalities (thinness, stenosis, tortuousity, lack of lateral marginal vein or postero-lateral vein). The incidence of thin and tortuousity was significantly higher in lateral marginal vein than that in postero-lateral vein (P < 0.05-0.01). The incidence of lack of postero-lateral marginal vein was more frequent than the lack of lateral vein (P < 0.05). The rate of abnormality in both vessels was 25.2%. Incidence of vein lack in male was more frequent than in female (P < 0.05). The thin and tortuousity of vessels in female were more frequent than in male (P < 0.05). The incidence of thin and tortuousity of postero-lateral and abnormality of both vessels was significantly higher in IHD than in NIHD patients (P < 0.05). All coronary sinus myocardial bridges occurred in NIHD. Stenoses of left anterior descending (LAD) and left circumflex (LCX) were mostly associated with abnormality of lateral vessels. CONCLUSIONS: The anatomic variations of lateral and postero-lateral coronary vein were more frequent in this patient cohort. Vein lack in male was more frequent and the thin and tortuousity of vessels were less in male than in female patients. The ratio of vessel abnormality is higher in patients with IHD. Coronary arteries stenosis and position of infarction are associated with anatomic variations of coronary vein system. PMID- 21033135 TI - [Efficacy and safety of intravenous levosimendan compared with dobutamine in decompensated heart failure]. AB - OBJECTIVE: To compare the efficacy and safety of intravenous levosimendan and dobutamine in patients with decompensated heart failure refractory to conventional medications. METHODS: Patients were recruited into this multicentre, randomised, positive-controlled and parallel-group study to receive either levosimendan or dobutamine therapy. In the levosimendan group, an initial loading dose of levosimendan of 12 microg x kg was infused over 10 min, followed by a continuous infusion of 0.1 microg x kg(-1) x min(-1) for 1 h and then 0.2 microg x kg(-1) x min(-1) for 23 h. In the control group, dobutamine was infused for 1 h at an initial dose of 2 microg x kg(-1) x min(-1) without a loading dose, followed by a continuous infusion of 4 microg x kg(-1) x min(-1) for 23 h. Hemodynamic responses at 24 h were evaluated by echocardiography (in both groups) and Swan-Gans catheter (in the levosimendan group). Clinical assessment was performed to evaluate efficacy and safety of the medications. RESULTS: A total of 225 patients from 12 medical centers were evaluated; 119 assigned to levosimendan and 106 assigned to dobutamine group. The effectiveness rate was 31.9% (38 patients) in the levosimendan group and 17.9% (19 patients) in the dobutamine group (P < 0.01). At 24 h, left ventricular ejection fraction (LVEF) was improved by 6. 4% in the levosimendan group, compared with 4.6% in the dobutamine group (P > 0.05). Stroke volume (SV) was increased by 11.1 ml in the levosimendan group and 2.8 ml in the dobutamine group respectively (P < 0.05). Dyspnea and clinical manifestations improvements were more significant in levosimendan therapy group compared to dobutamine group. There were less adverse effects including hypokalemia, hypotension and ventricular premature beats in the levosimendan group than in the dobutamine group (P < 0.05). CONCLUSION: Levosimendan was well tolerated and superior to dobutamine for patients with decompensated heart failure refractory to conventional medications. PMID- 21033136 TI - [Angiotensin-(1-7) reduced postangioplasty vascular fibrosis in abdominal aorta of rabbits]. AB - OBJECTIVE: To explore the effects of Angiotensin (ANG)-(1-7) on postangioplasty fibrotic remodeling and the involvement of TGF-beta/Smad signaling pathway in this process. METHODS: Thirty two healthy New Zealand white rabbits were randomly divided into 4 groups: sham group, control group, ANG-(1-7) group and ANG-(1-7) + A-779 group. Rabbits underwent angioplasty in the abdominal aorta or sham surgery. Subsequently, an osmotic minipump was implanted for saline, ANG-(1-7) (576 microg x kg(-1) x d(-1)) or ANG-(1-7) + A-779 (576 microg x kg(-1) x d(-1)) delivery. Before and after 4 weeks treatment, the levels of ANG II in plasma were measured by ELISA. At week 4, angiography and histomorphometric analysis were performed, mRNA levels of collagen I and III were assayed by RT-PCR and protein levels of TGF-beta1 and Smad2 in local vessel were assayed by Western blot. RESULTS: Following 4 weeks treatment, ANG-(1-7) and ANG-(1-7) + A-779 group displayed a significant elevation in lumen diameter [(4.11 +/- 0.10) mm and (3.34 +/- 0.11) mm vs. (2.88 +/- 0.08) mm, P < 0.05, respectively] and reduction in neointimal thickness [(208 +/- 17) microm and (407 +/- 25) microm vs. (448 +/- 15) microm, P < 0.05, respectively], neointimal area [(0.27 +/- 0.09) mm2 and (0.38 +/- 0.01) mm2 vs. (0.41 +/- 0.02) mm2, P < 0.05, respectively] and restenosis rate [(28.1 +/- 2.7)% and (36.8 +/- 2.2)% vs. (40.1 +/- 2.7)%, P < 0.05, respectively] compared with control group. Collagen I, III mRNA and TGF beta1, Smad2 protein levels were significantly elevated in control group, ANG-(1 7) group and ANG-(1-7) +A-779 group compared to sham group (P < 0.01 or P < 0.05) and reduced in ANG-(1-7) group compared to control group (all P < 0.05). Co treatment with A-779 reversed the inhibitory action of ANG-(1-7). Plasma levels of ANG II postangioplasty were similar in control and ANG-(1-7) group and both were significantly higher than preoperation levels. CONCLUSION: ANG-(1-7) attenuates postangioplasty collagen synthesis in rabbits possibly through down regulating the expression of TGF-beta1 and inhibiting the activation of Smad2 pathway. PMID- 21033137 TI - [Gradual algorithm of postconditioning reduced reperfusion injury through mitochondrion pathway in rats]. AB - OBJECTIVE: The effects of various postconditioning algorithm on reperfusion injury and the role of mitochondrion pathway were investigated in a rat model of reperfusion/injury. METHODS: Rats were divided into 5 groups: sham, reperfusion/injury (R/I group), reverse algorithm of postconditioning (R-Post, 30/10-25/15-15/25-10/30 s of reperfusion/re-occlusion), standard algorithm of postconditioning (S-Post, 4 cycles of 20/20 s of reperfusion/re-occlusion), and gradual algorithm of postconditioning (G-Post, 10/30-15/25-25/15-30/10 s of reperfusion/re-occlusion). RESULTS: The levels of Bax, Cytochrome-c, Caspase-9, serum marker of myocardium and apoptosis index were significantly lower while the level of Bcl-2 was significantly higher in the three postconditioning groups than those in R/I group (all P < 0.05). The levels of Bax (0.35 +/- 0.10 vs. 0.50 +/- 0.02, P < 0.05), Cytochrome-c (0.66 +/- 0.16 vs. 1.68 +/- 0.22, P < 0.05), Caspase-9 (0.61 +/- 0.17 vs. 1.66 +/- 0.55, P < 0.05), serum marker of myocardium [CK: (251.00 +/- 45.16) U/L vs. (388.56 +/- 75.01) U/L, P < 0.05; CK-MB: (146.00 +/- 60.12) U/L vs. (291.16 +/- 52.41) U/L, P < 0.05] and apoptosis index [(4.32 +/- 1.16)% vs. (8.58 +/- 1.12)% , P < 0.05] were all significantly lower while Bcl-2 level (2.00 +/- 0.34 vs. 1.40 +/- 0.18, P < 0.05) was significantly higher in G-Post group than those in S-Post group. Moreover, above mentioned cardiac protective effects were significantly stronger in the G-Post group compared to R Post group (all P < 0.05). CONCLUSION: In conclusion, gradual algorithm of postconditioning could attenuate reperfusion injury more significantly than standard algorithm, and mitochondrion pathway plays an important role in this cardioprotective process. PMID- 21033138 TI - [Feasibility of in vivo isotope labeled autologous mononuclear bone marrow cells monitoring post cardiac transplantation in a swine model of myocardial infarction]. AB - OBJECTIVE: To observe in vivo stem cell distribution and viability after transplantation by noninvasive imaging of 18F-fluorodeoxyglucose (18F-FDG) labeled autologous mononuclear bone marrow cells. METHODS: Myocardial infarction was established in 8 swine by ligating left anterior descending coronary artery after anesthesia. Bone marrow (20 ml) was drawn through ileum. After isolation, mononuclear bone marrow cells were labeled by radionuclide 18F-FDG and intramyocardially injected into infarction region. Whole body planar scan and myocardial tomography scan were performed immediately, 1 h, 2 h, and 3 h post stem cell injection. Viability and stability of radionuclide labeled stem cells were determined at 3 h post labeling in vitro. RESULTS: The labeling efficiency was (67 +/- 14)%. Mean dose of radioactive in marrow cells was (32 +/- 7) MBq. Trypan blue staining showed in vitro viability was (95 +/- 3)% at 3 h post labeling. After intramyocardial injection, labeled mononuclear bone marrow cell retention rate in infarction region was (83 +/- 6)%, (49 +/- 8)%, (32 +/- 6)% and (24 +/- 5)% immediately, 1 h, 2 h, and 3 h post injection, respectively. CONCLUSIONS: Distribution and viability of stem cell after cardiac transplantation could be effective monitored by 18F-FDG labeled autologous mononuclear bone marrow cell technique in acute stage in this model. PMID- 21033139 TI - [Restitution of atrial repolarization and atrial fibrillation in canine atrium]. AB - OBJECTIVE: Electrical restitution was believed to be a determinant responsible for the stability of heart rhythm. Although numerous studies focused on the role of action potential duration restitution (APDR) in the initiation and maintenance of ventricular fibrillation (VF), the relationship between atrial APDR and atrial fibrillation (AF) has not been fully understood. This study aims to investigate the characteristics of APDR of left atrium (LA) and right atrium (Rs) in canines and the relevance to induction of AF. METHODS: Monophasic action potential (MAP) was recorded from LA and RA in 14 canines using the MAP recording-pacing combination catheter. APDR, plotted as action potential duration (APD) on the preceding diastolic interval (DI), was assessed by use of programmed stimulation with a single extrastimulus (S1S2) at LA and RA. Episodes of AF were recorded and analyzed. RESULTS: APD90 was significantly shorter in the LA than that in the RA [(157.4 +/- 43.5) ms vs. (170.9 +/- 37.9) ms, P < 0.05]. The mean slope of the APDR curve by S1S2 in the LA was significantly greater than that in the RA (1.3 +/- 0.4 vs. 0.9 +/- 0.3, P < 0.05). The incidence of induced AF was significantly higher in the LA than in the RA (11/18 vs. 7/18, P < 0.05). CONCLUSIONS: The APDR and MAP characteristics are not uniform between atrium, which may be one of the important mechanisms responsible for the initiation of AF. Heterogeneity of APDR between LA and RA might create critical gradients or a dispersion of repolarization and substrate for re-entrant arrhythmias and vulnerability to AF. PMID- 21033140 TI - [Distribution characteristics and risk factors of carotid atherosclerosis in middle-aged and elderly Chinese]. AB - OBJECTIVE: To describe the distribution characteristics of carotid atherosclerosis and to analyze its association with cardiovascular risk factors in middle-aged and elderly Chinese. METHODS: In 2007, the second cross-sectional examination for cardiovascular risk factors and B-mode ultrasound imaging on carotid arteries were performed in a Chinese population consisting of 2681 subjects aged 43-81 years old from two cohorts participants of the People's Republic of China/United States of America collaborative study (USA-PRC study) and the Chinese multi-provincial cohort study (CMCS). The association of cardiovascular risk factors with intima-media thickening (ITM) and plaque of carotid arteries was analyzed. RESULTS: (1) The mean intima-media thickening (Mean-IMT) of carotid artery was 0.68 mm, the maximal intima-media thickening (Max-IMT) was 1.07 mm. (2) The prevalence rate of carotid plaque was 60.3% in all subjects. As for the different sites of carotid arteries, the plaque prevalence rate at carotid bulb was 61.2% for male and 51.6% for female (chi2 = 23.44, P < 0.01), and at the internal carotid artery was 24.7% for male and 12.2% for female (chi2 = 69.57, P < 0.01), at the common carotid artery was 20.9% for male and 13.8% for female (chi2 = 23.18, P < 0.01). (3) After adjusting for age and other cardiovascular risk factors, the Mean-IMT and Max-IMT increased with elevated levels of systolic blood pressure, plasma glucose and low density lipoproteins cholesterol (LDL-C) (all P < 0.05). Hypertension, diabetes, smoking and high LDL C (P < 0.05) were independent predict factors for the risk of carotid plaque. CONCLUSION: The carotid atherosclerosis was common in middle and older age Chinese and was positively associated with classical cardiovascular disease risk factors. PMID- 21033141 TI - [Time trends and age-related characteristics of cardio-cerebrovascular deaths in Hunan]. AB - OBJECTIVE: To investigate the time trends and age-related characteristics of mortality and disease burden for cardiocerebrovascular diseases (CVD) in Hunan, China during three periods (1973-1975, 1990-1992 and 2004-2005). METHODS: The cardiocerebrovascular death data of Hunan residents were collected by three national retrospective sample surveys of death. Cause-specific mortality, proportion, years of potential life lost (YPLL) and associated indicators were identified in the population of Hunan in above mentioned three periods. Time trends of age-specific mortality rate were assessed by fitting curvilinear regression lines and the increase rates of mortality with age were analyzed in each period. RESULTS: The standard all-cause mortality of residents in Hunan decreased (chi2 = 189.947, P < 0.001, chi2 = 54.201, P < 0.001; chi2 = 27,396.898, P < 0.001) while the standard mortality for CVD increased (chi2 = 54.201, P < 0.001; chi2 = 27,396.898, P < 0.001) from 1973 to 2005. The age specific mortality rate for CVD increased with age in all three periods, especially for citizens older than 60 years. There were age stages in each period in which the mortality increase rate was the fastest (10-14 and 15-19 years old in 1973-1975; 10-14, 15-19 and over 80 years old in 1990-1992; 15-19 and over 80 years old in 2004-2005). Exponential regression function (y = b0e(b1x)) can be used for the proper description of age-specific mortality change. The ratio of YPLL for CVD in all death causes showed increase trend (chi2 = 275,630.407, P < 0.001). YPLL rate (YPLLs per 1000) in 1973-1975 was higher than those in 1990 1992 and 2004-2005. YPLL rate was positively correlated with mortality in all periods. CONCLUSIONS: The mortality for CVD increased with time and aging. People older than 60 years were threatened by CVD mostly. Mortality trend analysis also found higher CVD deaths in people age 15-19 in Hunan residents. PMID- 21033142 TI - [Prevalence and awareness of dyslipidemia among overweight and obese population in Beijing community]. AB - OBJECTIVE: To investigate the prevalence and percentage of dyslipidemia awareness among overweight and obese residents in Beijing community. METHOD: Cross sectional data of 9786 subjects from capital cholesterol education and intervention program (CCEIP) were analyzed. Participants were divided into 3 groups (Normal, overweight and obese) based on body mass index (BMI). Blood lipid levels were determined from overnight fasting plasma samples. Questionnaires were collected to estimate awareness of dyslipidemia. RESULT: (1) Blood lipids levels were positively correlated with BMI (r = 0.17, 0.18, -0.26 and 0.35 between total cholesterol, LDL cholesterol, HDL cholesterol, triglyceride and BMI, respectively, all P < 0.01). (2) Prevalence of dyslipidemia increased in proportion with increase of BMI. The age-standardized prevalence of dyslipidemia of normal, overweight and obese population was 23. 9%, 43.3% and 65.4% in men and 17.9%, 29.2% and 42.3% in women. Dyslipidemia was more frequent in obese men than obese women (65.4% vs. 42.3%, P < 0.01). However, this gender difference decreased gradually with the increase of age. Risk of hypercholesterolemia, high LDL-C, low HDL-C and hypertriglyceridemia in obese men was 1.6, 2.9, 2.4, and 2.7 folders higher than in the normal body weight men and was 1.3, 1.9, 1.7 and 2.1 folders higher in obese women than in normal body weight women. (3) Unexpectedly, the percentage of dyslipidemia awareness in overweight and obese population was not significantly higher than in the normal body weight group (P > 0.05). CONCLUSION: The prevalence of dyslipidemia was high while the percentage of dyslipidemia awareness was rather low in obese population. Aggressive intervention should be taken in obese population, especially in the young obese men, to effectively reduce dyslipidemia. PMID- 21033143 TI - [Progress on renal sympathetic nerve activity and catheter renal sympathetic denervation in hypertension]. PMID- 21033144 TI - [Association between non-alcoholic fatty liver disease and atherosclerosis]. PMID- 21033145 TI - [Medical dyslipidemia intervention and vascular residual risks reduction]. PMID- 21033146 TI - [Relationship between activation of microglia and Jaks phosphorylation induced by microwave irradiation]. AB - OBJECTIVE: To explore the relationship between microglial proinflammatory and electromagnetic radiation and unveil the role of microglia in microwave radiation induced central nervous system injury. METHODS: N9 microglia cells cultured in vitro were exposed to microwave at 90 mW/cm2. Cell flow cytometry was used to observe the expression of CD11b at different time points after exposure; ELISA was used to detect the concentration of TNF-alpha in N9 cell culture supernatant; RT-PCR analysis confirmed iNOS mRNA expression in N9 microglia cells; and Nitrate Reductase Method was used to test NO amount in culture supernatant. RESULTS: The CD11b positive microglial cells increased significantly at 3 h after microwave exposure (P < 0.05), continued to increase until 24 h and peaked at 6 h after exposure. The amount of TNF-alpha rose dramatically from 1 h to 24 h after exposure (P < 0.01) and peaked at 3 h [(762.1 +/- 61.5) pg/ml] after exposure (P < 0.01). The level of NO started to increase at 1 h [(4.48-0.59) micromol/L] and lasted for 24 h after exposure. The expression of iNOS mRNA increased significantly at 1 h (P < 0.05), and tripled the original expression at 6 h after exposure, hereafter, it decreased slightly, but all were higher than the control group within 24 h after exposure. CONCLUSION: Microwave radiation could induce the activation of microglia cells. The activated microglia cells could induce microglial proinflammatory by producing large amounts of TNF-alpha, NO, etc. PMID- 21033147 TI - [Predictors of return to work after occupational injury in a locomotive enterprise]. AB - OBJECTIVE: To identify the potential determinants of return to work (RTW) following work-related injury. METHODS: A historical cohort of workers with occupational injury in a state-owned locomotive vehicle company in central China was followed up for RTW. Demographic, employment and medical information was retrieved from the company archival documents; and post-injury information was interviewed by questionnaires. Univariate analysis and Cox Regression Model were used to examine the associations between potential determinants and outcomes of RTW. RESULTS: Three hundred of the 323 included cases (92.9%) eventually returned to work after the median absence of 43 days (average of 49.2 days). Factors from socio-demographic, clinical, economic and psychological domains were found affecting RTW in the univariate analyses. The multivariate analysis indicated that age, injury severity, injury locus, injury nature, pain in the injury locus, self-reported health status and pre-injury monthly salary were significant determinants of RTW. CONCLUSIONS: There are multidimensional factors affecting RTW after occupational injury. Proper clinical treatment and rehabilitation, as well as economic and social support to facilitate workers' RTW would be the priorities for intervention. Future studies should be conducted in a larger representative sample to confirm the findings and to develop a multidisciplinary intervention strategy towards promoting RTW. PMID- 21033148 TI - [Occupational hygiene control over trichloroethylene occupational disease hazards in primary care organizations]. PMID- 21033149 TI - [Effects of high-frequency electromagnetic field on morphology of hippocampal cells in female rats]. AB - OBJECTIVE: To analyze the effects of high-frequency electromagnetic field (HF EMF, 30 MHz, 0-1600 V/m) on the apoptosis and ultramicrostructure of the hippocamp and demonstrate the cytotoxicity of hippocamp. METHODS: 120 Wistar female adult rats were randomly divided into ten groups based on body weight with different levels of 30 MHz electromagnetic field (0, 25, 100, 400, 1600 V/m) for eight hours daily. Five group rats were irradiated for three days. The other five group rats were irradiated for fifty-six days. Weekly the rats were continuously exposed five days. The apoptotic rate of the hippocamp was detected with TUNEL System. Meanwhile, the ultramicrostructure was observed with the transmission electron microscope. RESULTS: (1) There was no significant difference on the apoptotic rate and pathological change of the hippocamp cell between the exposure and the control groups through short term experiment (P > 0.05). (2) The apoptotic rate of the granulocyte on the DG campus of the hippocamp in the 400 V/m group and the 1600 V/m group (0.165% +/- 0.049%, 0.189% +/- 0.049% respectively) were increased significantly (P < 0.01) through inferior chronic experiment compared with the control group (0.052% +/- 0.016%). Along with the increase of radiation dose, the ultramicrostructure of the neuron cell appeared more abnormal cells. Especially there were marked change on the neuron in the 1600 V/m group. CONCLUSIONS: There is no association between cell apoptotic rate of the hippocamp and short period exposure to HF-EMF (30 MHz, 25-1600 V/m). However inferior chronic exposures to HF-EMF might induce the cytotoxicity, especially in the high dose exposure (1600 V/m) under our experiment. PMID- 21033150 TI - [Investigation on occupational exposure to 5-fluorouracil in pharmacy intravenous admixture service of a hospital]. AB - OBJECTIVE: To investigate the level of occupational exposure to 5-fluorouracil (5 Fu) in the pharmacy intravenous admixture service (PIVAS) of a hospital, and identify the sources of 5-Fu contamination. METHODS: The 5-Fu concentrations in air, on the surface of different areas in PIVAS and personal protective equipments were detected using UV-vis spectrophotometry. RESULTS: The 5-Fu in air could not be detected. The 5-Fu concentrations on five different surfaces of biological safety cabinets were (22.00 +/- 6.35), (13.99 +/- 2.46), (14.13 +/- 0.72), (7.25 +/- 1.19) and (9.87 +/- 1.23) ng/cm2, respectively, which were significantly higher than those [(3.14 +/- 0.04), (5.43 +/- 0.65), (2.26 +/- 0.17), (2.26 +/- 0.17) and (3.63 +/- 0.46) ng/cm2] of corresponding controls (P < 0.05 or P < 0.01). The 5-Fu concentrations of the floor under cabinets [(18.19 +/ 5.22) ng/cm2], the floor in front of cabinets [(10.25 +/- 2.57)ng/cm2], the office floor [(11.64 +/- 2.53) ng/cm2], the terrace floor [(99.89 +/- 14.06 ) ng/cm2], the floor beside trash can in dressing room [(24.54 +/- 0.23) ng/cm2] were significantly higher than those of control [(3.36 +/- 0.11 ) ng/cm2] (P < 0.05 or P < 0.01). The 5-Fu concentrations of the tables in preparation room [(7.22 +/- l.04) ng/cm2] and the tables in office [(11.81 +/- 1.18) ng/cm2] were significantly higher than those of control [(5.56 +/- 0.14) ng/cm2] (P < 0.05 or P < 0.01). The 5-Fu concentrations of the indoor handle in preparation room were significantly higher than those of controls (P < 0.05 or P < 0.01). 5-Fu concentrations on the surfaces of outdoor handle and floor beside door in preparation room were not significantly increased compared with controls (P > 0.05). The 5-Fu concentrations on the surfaces of infusion bags, transfer box, transfer trays were significantly higher than those of controls (P < 0.05). The differences of 5-Fu concentrations between outer and inner masks and controls were not significant (P > 0.05). The 5-Fu concentrations of gloves of preparing and checking staffs were significantly higher than those of controls (P < 0.05 or P < 0.01). CONCLUSION: The preparing and checking process of 5-Fu and the treatment of medical wastes are major sources of 5-Fu contamination. PMID- 21033151 TI - [Cognitive quality of professional divers]. AB - OBJECTIVE: To explore and analyze the cognitive quality of professional divers. METHODS: 165 professional divers were tested with Raven's Standard Progressive Matrices (SPM), 80.8 Neural Type Measuring Form, etc. with 230 common people, 49 sailors and 66 trainee divers as control. RESULTS: There were significant difference among professional divers of different ages in the type of nerve activity, cognitive style, action stability, memory span, time reaction, the perception of space, act of attention and dark adaptation (P < 0.05); Over all, the cognitive quality of professional divers did not differ significantly in education level or working years (P < 0.05); Professional divers were superior to the common people in depth perception, cognitive style, act of attention, action stability, the perception of space and dark adaptation, but inferior to them in intelligence, memory span and time reaction (P < 0.05); There were significant difference in such cognitive indicators as the type of nerve activity, depth perception, kinesthetic memory, cognitive style, the perception of space and dark adaptation (P < 0.05); Compared with the trainee divers, professional divers were significantly better in the type of nerve activity, cognitive style, act of attention, action stability and the perception of space (P < 0.05). CONCLUSION: As a specified profession, diving needs some particular cognitive quality, while the profession itself would affect professional divers' cognitive ability to a certain extent. PMID- 21033152 TI - [Red blood cell on lymphocyte proliferation in rats with chronic unpredictable mild stress]. AB - OBJECTIVE: To study the changes of rat red blood cells on T, B lymphocytes proliferation in chronic unpredictable mild stress (CUMS). METHODS: Thirty Wistar rats were averagely divided into control group and the CUMS group. The relevant behavioral performance and red blood cells on lymphocytes proliferation Changes by MTT colorimetric were observed. RESULTS: After fourteen days, the growth of weight and organic coefficient of brain decreased in model group (P < 0.05), with a significantly reduced consumption and preference of sucrose solutions, and increased pure water consumption as compared with control group (P < 0.05). Plasma corticosterone levels peaked at seven days but on a declining trend after fourteen days. The rate of red blood cells on T, B lymphocyte proliferation in depression group was lower than non-stress in 7, 14, 21 days (P < 0.05). CONCLUSION: The repeated chronic mild stress stimulation can induce long-time changes in acts and activities and decrease the rate of red blood cells on T, B lymphocytes proliferation, which can provide a new experimental method to observe the red blood cell immune function under the stress. PMID- 21033153 TI - [Four cases of hydrogen sulfide chemical eye burning]. PMID- 21033154 TI - [Involvement of Toll-like receptor in silica-induced tumor necrosis factor alpha release from human macrophage cell line]. AB - OBJECTIVE: To characterize the role of Toll-like receptor 4 (TLR4) in silica induced production of tumor necrosis factor alpha (TNFalpha) from macrophage cell line. METHODS: The human macrophage cell line THP-1 was incubated with silica suspension. Cell media were collected and TNFalpha levels in the supernatants measured with ELISA. To examine the involvement of TLR4 in silica-induced TNFalpha release, the neutralizing antibody (HTA125) against human TLR4 receptor was employed to pretreat THP-1 cells prior to silica treatment. Moreover, murine macrophages expressing wild type or mutated TLR4 were also treated with silica to verify the effect of TLR4 in silica-induced TNFalpha release. RESULTS: Compared with the control group [(3.18 +/- 0.41) pg/ml], the TNFalpha release in cells exposed to 100 microg/ml silica for 4 h and 8 h [(4.71 +/- 0.84), (6.22 +/- 0.58) pg/ml, respectively] increased 1.48 and 1.96 fold, respectively. Pretreatment of THP-1 cells with 20 microg/ml HTA125 antibody significantly blocked silica induced TNFalpha release by 27%. Furthermore, the TNFalpha content released from cells expressing mutated TLR4 reduced by 30% in compared with that from the cells expressing wild type TLR4 after silica stimulation. CONCLUSION: TLR4 mediates silica-induced TNFalpha release from macrophages. PMID- 21033155 TI - [Effect of submarine training on antioxidant ability in submarine men]. AB - OBJECTIVE: To study the effect of the submarine training on the antioxidant ability of the submarine men. METHODS: 50 sea-training submarine men, 50 land training submarine men and 50 resting submarine men were randomly selected from some submarine troops. The blood routine, the total antioxidative capacity (T AOC), the content of malondialdehyde (MDA) and the levels of IFN-gamma in blood plasma, the hemolytic degree of RBC, the proliferation of peripheral-blood lymphocyte (PPL) of them were detected in each group. RESULTS: The T-AOC of the sea-training submarine men, the land-training submarine men and the resting submarine men significantly increased by turns [(15.38 +/- 3.11), (18.81 +/- 2.45), (20.93 +/- 2.95) U/ml], but MDA and the hemolytic degree of RBC significantly decreased by turns [(2.56 +/- 0.70), (2.12 +/- 0.53),(1.77 +/- 0.56) nmol/ml and 25.72% +/- 1.67%, 21.45% +/- 1.02%, 18.28% +/- 1.37%] (P < 0.05). Compared with the land-training submarine men and the resting submarine men, IFN-gamma [(31.89 +/- 3.52) pg/ml] and the proliferation of PPL of the sea training submarine men were significantly lower, whereas the red blood count (RBC) and hemoglobin (Hb) were significantly higher (P < 0.05). CONCLUSION: Submarine training, especially sea training, may decrease the antioxidant ability. PMID- 21033157 TI - [Non-fatal unintentional injuries and risk factors among male farmers-turned construction workers with different age groups]. PMID- 21033156 TI - [Investigation on dermal contamination among workers occupationally exposed to dimethylformamide]. AB - OBJECTIVE: To establish a method for the determination of dimethylformamide (DMF) and investigate dermal contamination and absorption among workers occupationally exposed to DMF. METHOD: 37 workers exposed to DMF were divided randomly into two groups. DMF was washed down by isopropyl alcohol in A group (16 workers) and water in B group(21 workers).Gas chromatography was used for the quantification of dermal contamination and N-methylformamide(NMF) in urine, correlative study was done between them. RESULTS: DMF could be detected in all samples in A group, but could not be detected in B group. The miscellaneous peaks could be completely separated from the DMF peak in the sample spectrum, without manual inference. The highest degree of total dermal contamination was observed in wet spinning workshop [(2.84 +/- 1.31) mg], postprocessing workshop [(2.50 +/- 0.95) mg] and dry spinning workshop [(1.95 +/- 0.61) mg] were lower. The respiratory cumulative exposure dosages were 351.3, 201.3 and 135.2 mg respectively. The average DMP concentration in air of the third printing processing workshop, the dry spinning workshop and the wet spinning workshop was 60.2, 89.6, 156.4 mg/m3 respectively, and the respiratory tract contamination in the workers of the three workshops were 135.2, 201.3 and 351.3 mg respectively. There was statistical independence between the quantification of total dermal contamination and NMF in urine (r = 0.176, P > 0.05). CONCLUSION: Isopropyl alcohol is the effective washing solvent.When the concentration of DMF in workplace air is above the occupational exposure limit, respiratory tract absorption is the principal pathway of DMF absorption,but dermal contamination of DMF should not be ignored. PMID- 21033158 TI - [Analysis of acute occupational poisoning accidents in a city between 1986 and 2005]. PMID- 21033159 TI - [Investigation on occupational hygiene status quo of medical waste processing enterprises in a province]. PMID- 21033160 TI - [Trend of radon concentration day change in greenhouse and impact factors]. PMID- 21033161 TI - [Influence of long-term microwave radiation on contents of amino acids and monoamines in urine of Wistar rats]. PMID- 21033162 TI - [Pre-exposure with hyperbaric oxygen reduces incidence of decompression sickness in rats]. PMID- 21033163 TI - [Effects of TCDD on Na+ K+ AtPase and Ca2+ ATPase in brain of mice]. PMID- 21033164 TI - [Analysis of direct network report of occupational diseases in Guangzhou between 2007 and 2008]. PMID- 21033165 TI - [Correlation between myocardial injury induced by acute carbon monoxide poisoning and NT proBNP]. PMID- 21033166 TI - [Clinical analysis of fishermen's eye burns and mild poisoning induced by H2S]. PMID- 21033167 TI - [Comparison between digital X-ray imaging and high voltage X-ray imaging in diagnosis of pneumoconiosis]. PMID- 21033168 TI - [Role of ceramide in cell stress response]. PMID- 21033169 TI - [Progress in research on deep mine thermal injury to human health]. PMID- 21033170 TI - [Progress in research on explosion deafness]. PMID- 21033171 TI - [Clinical analysis of occupational acute acrylonitrile poisoning]. PMID- 21033172 TI - [One case of acute yellow phosphorus poisoning]. PMID- 21033174 TI - [Overtime working and work accident]. PMID- 21033173 TI - [13 cases of Abamectin poisoning]. PMID- 21033175 TI - [Influential factors of occupational hygiene strategy execution]. PMID- 21033176 TI - [Effect of benzene exposure at low dose for a long term on regulatory T cells in peripheral blood]. PMID- 21033177 TI - [Complicated non-steady state noise induced hearing injury of workers]. PMID- 21033178 TI - [Comparison between application of membrane valve and plastic valve]. PMID- 21033179 TI - [Cerebral amyloid angiopathy]. PMID- 21033180 TI - Carbon monoxide poisoning deaths associated with camping - Georgia, March 1999. AB - Carbon monoxide (CO) is an odorless, colorless, nonirritating gas produced by the incomplete combustion of carbon-based fuels. CO exposure is responsible for more fatal unintentional poisonings in the United States than any other agent, with the highest incidence occurring during the cold-weather months (1 ). Although most of these deaths occur in residences or motor vehicles (2 ), two incidents among campers in Georgia illustrate the danger of CO in outdoor settings. This report describes the two incidents, which resulted in six deaths, and provides recommendations for avoiding CO poisoning in outdoor settings. PMID- 21033181 TI - Four pediatric deaths from community-acquired methicillin-resistant Staphylococcus aureus - Minnesota and North Dakota, 1997-1999. AB - Methicillin-resistant Staphylococcus aureus (MRSA) is an emerging community acquired pathogen among patients without established risk factors for MRSA infection (e.g., recent hospitalization, recent surgery, residence in a long-term care facility [LTCF], or injecting-drug use [IDU]) (1). Since 1996, the Minnesota Department of Health (MDH) and the Indian Health Service (IHS) have investigated cases of community-acquired MRSA infection in patients without established risk factors. This report describes four fatal cases among children with community acquired MRSA; the MRSA strains isolated from these patients appear to be different from typical nosocomial MRSA strains in antimicrobial susceptibility patterns and pulsed-field gel electrophoresis (PFGE) characteristics. PMID- 21033182 TI - Gastrointestinal basidiobolomycosis-Arizona, 1994-1999. AB - In March 1999, the Arizona Department of Health Services (ADHS) notified CDC about six cases of gastrointestinal basidiobolomycosis (GIB), an invasive fungal infection. Three cases were reported during January-March 1999, compared with three cases reported during the previous 5 years. This report describes two persons who had representative clinical presentations and summarizes the findings of the investigation of these cases, which indicate that this unusual fungal infection causes severe illness and may be misdiagnosed initially. PMID- 21033183 TI - Iron deficiency anemia in Alaska native children-Hooper Bay, Alaska, 1999. AB - During fall 1998, health-care providers in Hooper Bay, Alaska, reported that hemoglobin data from a local Head Start program indicated that 14 (31%) of the 45 children aged 2-4 years had anemia (hemoglobin <11.0 g/dL), with an overall mean hemoglobin of 11.2 g/dL (standard deviation [SD] +/- 1.3 g/dL) (CDC, unpublished data, 1996-1997). This proportion was substantially higher than the estimated prevalence in the United States of 8% among children aged 1-5 year (1). Because the region's economy is heavily dependent on fishing and the region experienced a poor salmon run in 1998, the Alaska State Health Department was concerned that economic hardships could exacerbate the anemia problem. In January 1999, CDC and the Yukon-Kuskokwim Health Corporation assessed the prevalence of anemia among Hooper Bay children aged 1-5.9 years to determine factors contributing to anemia in this population, and to identify recommendations for potential interventions. The findings indicated that the estimated prevalence of anemia among these children was more than twice the U.S. average. PMID- 21033184 TI - State systems Advance Planning Document (APD) process. Final rule. AB - The Advance Planning Document (APD) process governs the procedure by which States obtain approval for Federal financial participation in the cost of acquiring automated data processing equipment and services. This final rule reduces the submission requirements for lower-risk information technology (IT) projects and procurements and increases oversight over higher-risk IT projects and procurements by making technical changes, conforming changes and substantive revisions in the documentation required to be submitted by States, counties, and territories for approval of their Information Technology plans and acquisition documents. PMID- 21033185 TI - The contradictions of juvenile crime & punishment. PMID- 21033194 TI - Science, conscience, consciousness. AB - Descartes' metaphysics lays the foundation for the special sciences, and the notion of consciousness ("conscientia") belongs to metaphysics rather than to psychology. I argue that as a metaphysical notion, "consciousness" refers to an epistemic version of moral conscience. As a consequence, the activity on which science is based turns out to be conscientious thought. The consciousness that makes science possible is a double awareness: the awareness of what one is thinking, of what one should be doing, and of the possibility of a gap between the two. PMID- 21033193 TI - Introduction. AB - The history of the science of consciousness is difficult to trace because it involves an ongoing debate over the aims involved in the study of consciousness that historically engaged people working in a variety of different, often overlapping, philosophical projects. At least three main aims of these different projects can be identified: (1) providing an ultimate foundation for natural science; (2) providing an empirical study of experience; and (3) promoting human well-being by relieving suffering and encouraging human flourishing. Each of these aims has its own problems and its own methods for solving them that endorse different epistemic virtues characteristic of science in different historical periods through a variety of "styles of science". PMID- 21033195 TI - Ralph Cudworth and the theological origins of consciousness. AB - The English Neoplatonic philosopher Ralph Cudworth introduced the term "consciousness" into the English philosophical lexicon. Cudworth uses the term to define the form and structure of cognitive acts, including acts of freewill. In this article I highlight the important role of theological disputes over the place and extent of human freewill within an overarching system of providence. Cudworth's intellectual development can be understood in the main as an increasingly detailed and nuanced reaction to the strict voluntarist Calvinism that is typified in the thought of his near contemporary William Perkins. At the heart of Cudworth's rejection of Calvinism is the dilemma over whether God is understood primarily in terms of will or justice. In this fleshing-out of the power of consciousness Cudworth moves from an instrumental account of the working of the human mind towards an account of human consciousness that is intrinsic to his definition of human agency. PMID- 21033196 TI - Kant and the scientific study of consciousness. AB - We argue that Kant's views about consciousness, the mind-body problem and the status of psychology as a science all differ drastically from the way in which these topics are conjoined in present debates about the prominent idea of a science of consciousness. Kant never used the concept of consciousness in the now dominant sense of phenomenal qualia; his discussions of the mind-body problem center not on the reducibility of mental properties but of substances; and his views about the possibility of psychology as a science did not employ the requirement of a mechanistic explanation, but of a quantification of phenomena. This shows strikingly how deeply philosophical problems and conceptions can change even if they look similar on the surface. PMID- 21033197 TI - Is routine surgical patient follow-up required? PMID- 21033198 TI - Mathematics, experience and laboratories: Herbart's and Brentano's role in the rise of scientific psychology. AB - In this article we present and compare two early attempts to establish psychology as an independent scientific discipline that had considerable influence in central Europe: the theories of Johann Friedrich Herbart (1776-1841) and Franz Brentano (1838-1917). While both of them emphasize that psychology ought to be conceived as an empirical science, their conceptions show revealing differences. Herbart starts with metaphysical principles and aims at mathematizing psychology, whereas Brentano rejects all metaphysics and bases his method on a conception of inner perception (as opposed to inner observation) as a secondary consciousness, by means of which one gets to be aware of all of one's own conscious phenomena. Brentano's focus on inner perception brings him to deny the claim that there could be unconscious mental phenomena - a view that stands in sharp contrast to Herbart's emphasis on unconscious, "repressed" presentations as a core element of his mechanics of mind. Herbart, on the other hand, denies any role for psychological experiments, while Brentano encouraged laboratory work, thus paving the road for the more experimental work of his students like Stumpf and Meinong. By briefly tracing the fate of the schools of Herbart and Brentano, respectively, we aim to illustrate their impact on the development of psychological research, mainly in central Europe. PMID- 21033199 TI - SILS and NOTES cholecystectomy: a tailored approach. PMID- 21033200 TI - Post laryngectomy speech and voice rehabilitation: past, present and future. PMID- 21033201 TI - Preoperative prediction of sepsis after aortic surgery. PMID- 21033202 TI - Thigh enlargement and the art of misdirection. PMID- 21033203 TI - A rare case of Schwannoma of the intrathoracic phrenic nerve. PMID- 21033204 TI - Diamonds in the rough: rare variants scratch the surface. PMID- 21033205 TI - The e-learning site. PMID- 21033206 TI - Wundt, Vygotsky and Bandura: a cultural-historical science of consciousness in three acts. AB - This article looks at three historical efforts to coordinate the scientific study of biological and cultural aspects of human consciousness into a single comprehensive theory of human development that includes the evolution of the human body, cultural evolution and personal development: specifically, the research programs of Wilhelm Wundt, Lev Vygotsky and Albert Bandura. The lack of historical relations between these similar efforts is striking, and suggests that the effort to promote cultural and personal sources of consciousness arises as a natural foil to an overemphasis on the biological basis of consciousness, sometimes associated with biological determinism. PMID- 21033207 TI - William James on a phenomenological psychology of immediate experience: the true foundation for a science of consciousness? AB - Throughout his career, William James defended personal consciousness. In his "Principles of Psychology" (1890), he declared that psychology is the scientific study of states of consciousness as such and that he intended to presume from the outset that the thinker was the thought. But while writing it, he had been investigating a dynamic psychology of the subconscious, which found a major place in his Gifford Lectures, published as "The Varieties of Religious Experience" in 1902. This was the clearest statement James was able to make before he died with regard to his developing tripartite metaphysics of pragmatism, pluralism and radical empiricism, which essentially asked "Is a science of consciousness actually possible?" James's lineage in this regard, was inherited from an intuitive psychology of character formation that had been cast within a context of spiritual self-realization by the Swedenborgians and Transcendentalists of New England. Chief among these was his father, Henry James, Sr., and his godfather, Ralph Waldo Emerson. However, james was forced to square these ideas with the more rigorous scientific dictates of his day, which have endured to the present. As such, his ideas remain alive and vibrant, particularly among those arguing for the fusion of phenomenology, embodiment and cognitive neuroscience in the renewed search for a science of consciousness. PMID- 21033208 TI - Narrating consciousness: language, media and embodiment. AB - Although there has long been a division in studies of consciousness between a focus on neuronal processes or conversely an emphasis on the ruminations of a conscious self, the long-standing split between mechanism and meaning within the brain was mirrored by a split without, between information as a technical term and the meanings that messages are commonly thought to convey. How to heal this breach has posed formidable problems to researchers. Working through the history of cybernetics, one of the historical sites where Claude Shannon's information theory quickly became received doctrine, we argue that the cybernetic program as it developed through second-order cybernetics and autopoietic theory remains incomplete. In this article, we return to fundamental questions about pattern and noise, context and meaning, to forge connections between consciousness, narrative and media. The thrust of our project is to reintroduce context and narrative as crucial factors in the processes of meaning-making. The project proceeds along two fronts: advancing a theoretical framework within which context plays its property central role; and demonstrating the importance of context by analyzing two fictions, Stanislaw Lem's "His Master's Voice" and Joseph McElroy's "Plus," in which context has been deformed by being wrenched away from normal human environments, with radical consequences for processes of meaning-making. PMID- 21033209 TI - Is propofol sedation with midazolam induction safe during endoscopic procedures without anesthesiologist? AB - BACKGROUND/AIMS: Sedation is important for the success and quality of endoscopy. We aimed to evaluate the safety of propofol during the endoscopy under supervision of a gastroenterologist without an anesthesiologist. METHODOLOGY: All propofol using endoscopic procedures between January 2004 and December 2008 were evaluated retrospectively. All patients received i.v. propofol plus midazolam during the procedures. Blood pressure, heart rate and pO2 saturation were all recorded before and during the procedures. RESULTS: Mean age of patients was 39.13 +/- 12.9 years (45% male). 50 endoscopic retrograde colangiography, 1430 colonoscopy, 2478 gastroscopy and 210 double balloon enteroscopy procedures were evaluated. First i.v. midazolam (mean 3 +/- 1.1 mg) was used for sedation, then i.v. propofol (mean dose 50 +/- 10 mg) was titrated to achieve deep sedation. Before the procedures, mean pO2, systolic blood pressure, and heart rate were 95 +/- 3%, 120 +/- 25 mmHg, 87 +/- 20, respectively. Mean pO2 decreased significantly during the procedures (from 95 +/- 3% to 83 +/- 5%) (p < 0.005). Only one patient needed tracheal intubation. Arterial hypotension (< 90 mmHg systolic pressure) was observed in 10% of patients (p > 0.05). Two percent of patients had bradycardia (Heart rate < 50 min). CONCLUSION: Using propofol after midazolam induction seems to be feasible only if the patients are carefully observed and their vital functions monitored during the procedures. PMID- 21033210 TI - Tumor lysis syndrome after sorafenib for hepatocellular carcinoma: a case report. AB - We encountered a patient who developed marked renal impairment and hyperuricemia in a short period after sorafenib administration, which suggested tumor lysis syndrome (TLS). A 79-year-old woman with hepatitis C-related liver cirrhosis was found to have intermediate hepatocellular carcinoma (HCC) according to Barcelona Clinic Cancer staging classification. Pre-treatment laboratory tests showed mild renal impairment. On the 10th day of sorafenib intake, the creatinine and uric acid levels rose to 2.99 and 16.1 mg/dl, respectively, and arterial blood gas analysis showed respiratory compensated metabolic acidosis, which suggested grade I clinical TLS according to the diagnostic criteria of TLS as defined by Cairo Bishop. TLS is a group of metabolic abnormalities that arise from the rapid breakdown of many tumor cells upon the initiation of malignant tumor chemotherapy, resulting in the release of intracellular metabolites that exceed the ability of the kidney to excrete them. TLS occurs more rarely in solid tumors, including HCC, than in hematologic malignancies. Sorafenib is administered to patients with renal impairment at recommended doses. However, the drug may cause TLS or severe renal impairment in advanced HCC patients with preexisting mild renal impairment, necessitating reduced-dose therapy and careful follow-up after the start of therapy to facilitate early diagnosis and treatment. This is a very rare complication developed in a short period treated with sorafenib as a single-agent for an advanced HCC. PMID- 21033211 TI - Usefulness of peroral cholangioscopy in preoperative diagnosis of intraductal papillary neoplasm of the bile duct. AB - Surgical resection is considered the first-line treatment of intraductal papillary neoplasm of the bile duct (IPNB). Since some patients with IPNB have an unexpectedly superficially-spreading lesion, preoperative cholangioscopic diagnosis is very useful in determining the extent of resection. We report a patient with IPNB in whom preoperative peroral cholangioscopic evaluation was useful. PMID- 21033212 TI - Measurement of serum marker for bone metastasis (1-CTP) in hepatobiliary and pancreas malignancies. AB - BACKGROUND/AIMS: Pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (1CTP) is a sensitive serum marker for metastatic bone carcinomas and may also be associated with invasiveness of various carcinomas. To clarify the significance of 1CTP in hepato-biliary pancreas malignancies, we examined the relationship between clinicopathological features and serum level of 1CTP. METHODOLOGY: The subjects were 75 patients who underwent surgical resections including 27 patients with liver carcinomas, 15 with extra-hepatic biliary carcinomas, 14 pancreatic carcinomas and 19 benign diseases. RESULTS: 1CTP level tended to be higher in the malignant diseases than in benign diseases but this difference was not significant (p = 0.065). Compared to benign adenoma, 1CTP level in the malignant diseases was significantly higher (p = 0.049). 1CTP level tended to be higher in patients with cholangitis compared to those with no inflammation or benign tumors (p = 0.065). 1CTP was not correlated with any tumor markers. 1CTP was not associated with node status and vascular infiltrations. 1CTP level tended to be lower in patients with poor differentiation. CONCLUSIONS: Serum level of 1CTP might be a predictive marker for hepatobiliary pancreas malignancies but also reflects the degree of co-existing cholangitis. PMID- 21033213 TI - Adequate preoperative biliary drainage is determinative to decrease postoperative infectious complications after pancreaticoduodenectomy. AB - BACKGROUND AND PURPOSE: To assess the effectiveness of preoperative biliary drainage (PBD) by preoperative serum bilirubin level in patients with periampullary lesions receiving pancreaticoduodenectomy. PATIENTS AND METHODS: Between Jan. 1995 to May 2005, 240 consecutive cases received pancreaticoduodenectomy at the National Cheng Kung University Hospital, Taiwan and were included retrospectively. Factors possibly affecting postoperative morbidity and mortality were analyzed. RESULTS: One hundred and forty-three patients (59.6%) underwent preoperative biliary drainage (the PBD group) and 97 patients without drainage (the non-PBD group). The total postoperative morbidity rate was 49.6% and postoperative mortality was 2.9%. There was no difference in total postoperative morbidity and mortality between groups, but higher incidence of sepsis/bacteremia in the PBD patients (p = 0.03), and more cardiovascular events (p = 0.05) in the non-PBD patients. More bile leakage developed in the non PBD patients, but only with marginal significance (p = 0.09). In the PBD group, patients with preoperative serum bilirubin level > or = 5 mg/dL had higher likelihood to acquire an infectious complication, (OR: 2.70; CI: 1.21-6.04), and surgical site infectious (OR: 2.70; CI: 1.21-6.04), intraabdominal abscess (OR: 2.74; CI: 0.94-8.03), and wound infection (OR: 2.44; CI: 0.97-6.16). CONCLUSION: Preoperative biliary drainage increased postoperative infectious complications but it also decreased cardiovascular events. However, adequate preoperative biliary drainage is the key to decrease infectious complications. PMID- 21033214 TI - Intraoperative ultrasonography for reducing bile duct injury during laparoscopic cholecystectomy. AB - BACKGROUND/AIMS: Laparoscopic cholecystectomy has become a standard procedure for gallstone disease. Bile duct injury during laparoscopic cholecystectomy is one of the most serious complications. The cause of such injury is usually the erroneous interpretation of bile duct anatomy, especially mistaking common bile duct for the cystic duct. A method for the prevention of this injury has not been established. The objective of this study was to test the usefulness of intraoperative ultrasonography for preventing bile duct injury. METHODOLOGY: We performed intraoperative ultrasonography to visualize the junction of the cystic duct and common bile duct before cannulation for intraoperative cholangiography. A total of 200 patients were enrolled in this study from May 2004 to November 2005. RESULTS: In 188 out of 200 cases (94%), the junction was identified by intraoperative ultrasonography before the cholangiography. CONCLUSION: Identification of the junction of the cystic duct and common bile duct before intraoperative cholangiography may reduce bile duct injury in laparoscopic cholecystectomy. PMID- 21033215 TI - Fecal RNA detection of cytokeratin 19 and ribosomal protein L19 for colorectal cancer. AB - BACKGROUND/AIMS: We attempted to specifically quantify transcripts of faecal cytokeratin 19 (CK19) and ribosomal protein L19 (RPL19) RNA expression of colorectal cancer and clarify their correlation with clinicopathological parameters and survival in combination. METHODOLOGY: Solid fecal samples were collected and preserved before any treatment. Levels of faecal CK19 and RPL19 mRNA were measured using quantitative real-time PCR. An expression level higher than median value was defined as positive. RESULTS: Between April 2001 and June 2007, 92 patients were recruited. The levels of both markers increased in a trend as stage. Young patients (< 67 years) were correlated with higher rate of CK19+ (p = 0.001), so were higher stages but with borderline significance (p = 0.051). CK19+ and RPL19+ were highly correlated mutually (p = 0.001). Neither CK19+ (p = 0.12) nor RPL19+ (p = 0.14) alone was a prognostic factor of disease-free interval. However, CK19+/RPL19+ was shown to be with worse prognosis (p = 0.037), but not an independent factor in multivariate analysis with stage. CONCLUSIONS: Both markers were significantly higher in the patients of metastatic disease. The use of two markers will recognize the high risk group better than the single marker usage, though not reaching independent status yet. Multi-target strategy assay is suggested for fecal RNA examination. PMID- 21033216 TI - Long-term outcome of laparoscopic surgery for T1 cancer patients of the colorectum. AB - BACKGROUND/AIMS: Many reports of laparoscopic colorectal surgery (LCS) for advanced cancer have been published indicating that LCS is an optimal and less invasive surgical treatment. On the other hand, there are few reports that address the early stages of cancer, especially with regard to the long-term outcome. This study analyzed the short- and long-term outcomes after LCS in patients with T1 cancer. METHODOLOGY: Between 1994 and 2005, a total of 135 LCS, including 129 laparoscopic colectomies and 6 laparoscopic anterior resections were performed in patients with T1 cancer that was diagnosed after the operation. The median follow-up was 83.5 months (range, 33-165). RESULTS: Postoperative complications included 6 wound infections (4%), 3 bowel obstructions (2%), 2 anastomotic leakage (1.3%), 1 atelectasis (0.67%). None of the patients required a re-operation. Oral intake was started after a mean of 2.9 postoperative days and the mean postoperative hospital stay was 14.4 days. There was no mortality and the overall survival was 100% in long-term follow up. CONCLUSIONS: LCS for T1 cancer is technically and oncologically safe based on the long-term outcomes when performed by surgeons with sufficient experience in laparoscopic techniques. PMID- 21033217 TI - Detection of colorectal neoplasm using promoter methylation of ITGA4, SFRP2, and p16 in stool samples: a preliminary report in Korean patients. AB - BACKGROUND/AIMS: Colorectal cancer (CRC) screening using stool DNA has yielded a greater detection rate than conventional fecal occult blood testing. The aim of this study was to determine the sensitivity and specificity of this detection method for colorectal adenomas and carcinomas using ITGA4, SFRP2 and p16 promoter methylation. METHODS: The methylation status of ITGA4, SFRP2 and p16 promoters in bisulfite-modified stool DNA was investigated in a blinded manner with methylation specific PCR (MSP) from 31 endoscopically diagnosed healthy controls, 25 patients with adenomas and 30 patients with CRC. RESULTS: Methylated ITGA4, SFRP2 and p16 promoters were detected in 36.7%, 60.0%, and 40.0% of the CRC samples and in 16.0%, 44.0%, and 24.0% of the colorectal adenomas, respectively. The sensitivity of the combined study using the three markers for CRC and colorectal adenoma detection was 70.0% and 72.0%. The specificity of this method was 96.8%. CONCLUSION: Our results demonstrate that ITGA4, SFRP2 and p16 promoter methylation in stool samples had high sensitivity and specificity for the detection of colorectal adenomas and CRC. This newly developed screening may be a useful non-invasive alternative screening for CRC detection. PMID- 21033218 TI - Factors that influence 12 or more harvested lymph nodes in resective R0 colorectal cancer. AB - BACKGROUND/AIMS: The number of lymph nodes required for accurate staging is a critical component in colorectal cancer (CRC). Current guidelines demand at least 12 lymph nodes to be retrieved. Results of previous studies were contradictory in factors, which influenced the number of harvested lymph nodes. This study was designed to determine the factors that influence the number of harvested lymph nodes (> or = 12) in resective R0 early-stage CRC in a single institution. METHODOLOGY: Between July 2005 and December 2008, data on 225 patients who underwent surgery for CRC were retrospectively evaluated. Data for a total of 139 R0-surgery patients were collected and all the tumor-bearing specimens were fixed with node identification performed. Several possible factors that influence 12 or more harvested lymph nodes were investigated and classified into four aspects: (1) operating surgeon, (2) examining pathologist, (3) patient (age, sex, and body mass index) and (4) disease (tumor localization, tumor cell differentiation, tumor stage, type of resection). RESULTS: A total of 100 patients (71.9%) with 12 or more harvested lymph nodes and 39 patients (28.1%) with < 12 lymph nodes were analyzed. The results demonstrate that within a single institution, tumor localization, depth of tumor invasion according to Dukes stage and grading were independent influencing factors of 12 or more harvested lymph nodes. Neither the operating surgeon nor the examining pathologist had significant influence on the number of harvested lymph nodes. CONCLUSIONS: The number of harvested lymph nodes was highly variable in patients who underwent resection of R0 CRC. Neither the operating surgeon nor the examining pathologist had significant influence over the number of harvested lymph nodes. Therefore, from the viewpoint of the surgeons, disease itself is the most important factor influencing the number of harvested lymph nodes. PMID- 21033219 TI - Expression of p16, p53, and Ki-67 in colorectal adenocarcinoma: a study of 356 surgically resected cases. AB - BACKGROUND/AIMS: The aim of the present study was to investigate the clinicopathological significance of p53, Ki-67, and p16 expression in patients with colorectal adenocarcinoma. METHODOLOGY: We evaluated p53, Ki-67, and p16 expression in 356 patients with primary colorectal adenocarcinoma using an immunohistochemical staining method. The relationships between these protein expressions and clinicopathological factors were statistically analyzed. RESULTS: Positive p53 staining was detected more often in typical adenocarcinoma compared to mucinous adenocarcinoma (49% versus 17%, p = 0.007) and in well or moderately differentiated adenocarcinoma compared to poorly differentiated adenocarcinoma (50% versus 32%, p = 0.030). The level of expression of p53 protein was related to lymph node metastasis (p < 0.001) and the TNM stage of the colorectal adenocarcinoma (p = 0.006). The p53 protein expression was related to an increased tendency of lymphovascular invasion (p = 0.058). However, Ki-67 and p16 expression levels were not associated with any of the clinicopathological variables. The overexpression of p53 was correlated with a higher level of Ki-67 (p = 0.001) and positive staining of p16 (p < 0.001). CONCLUSIONS: Our data suggest that overexpression of p53, which was correlated with Ki-67 and p16 expression, plays a critical role in aggressive tumor behaviors in patients with colorectal adenocarcinoma. However, further long-term followup studies are warranted to evaluate the clinical impacts of p53 in a larger group of patients. PMID- 21033220 TI - GLUT1 and Bcl-xL in relation to erythropoietin in human colorectal adenocarcinomas. AB - BACKGROUND/AIMS: GLUT1 and EPO belong to so called hypoxia-associated markers, which exert cytoprotective actions in the hypoxia suffering cells. In oxygen deficiency Bcl-xL can also be upregulated. METHODOLOGY: Therefore, we detected with immunohistochemistry and compared EPO with expressions of GLUT-1 and antiapoptotic protein Bcl-xL in 125 colorectal cancers. EPO correlated with GLUT 1 in all colorectal cancers (p < 0.001, r = 0.369). EPO expressions also associated with Bcl-xL (p < 0.001, r = 0.591) in all colorectal cancers. RESULTS: EPO correlated with GLUT-1 and Bcl-xL in subgroups of different nodal status, grading, staging, histopathological type, tumor site, patients' age and gender. However, the statistically significant relationship between EPO and GLUT-1 or Bcl xL was lost in case of shallower neoplastic extent (pT1+pT2), but it was sustained in subgroup of deeper invading cancers (pT3+pT4) (p < 0.001, r = 0.355 and p < 0.001, r = 0.585, respectively). CONCLUSIONS: High expression of hypoxia dependent proteins (EPO, GLUT-1) indicates hypoxia of examined tissues of colorectal cancers. Cooperation may be reflected among the studied proteins by correlations between hypoxia dependent proteins (EPO vs. GLUT-1). Concerning functional significance of these investigated factors, subsequent promotion of cell survival could be maintained thanks to mutual impact of EPO and Bcl-xL on cellular viability in hypoxic environment of colorectal cancer. PMID- 21033221 TI - Longer capsule endoscopy operation time increases the rate of complete examination of the small bowel. AB - BACKGROUND/AIMS: Wireless capsule endoscopes (CEs) have become a useful diagnostic tool for small bowel diseases, but they may fail to examine the entire small bowel. We analyzed the clinical experience of the MiRo CE in patients with suspected small bowel disease to assess whether longer operation time could increase the complete examination rate of the small bowel and diagnostic yield. METHODOLOGY: A total of 96 patients with suspected small bowel disease received CE examination at 4 tertiary hospitals in Korea. The recorded information was uploaded to a computer and analyzed by the physicians responsible for each patient. RESULTS: The average total capsule operation time was 11 hours and 39 minutes (range: 5 hours 18 minutes approximately 12 hours). In 87 (90.6%) out of 96 cases, the CE was able to explore the entire small bowel. In 32 cases (33.3%), it took more than 8 hours to reach the cecum. Capsule retention occurred in 2 cases (2.1%). The CE found meaningful small bowel lesions in 62 (64.6%) out of 96 total cases. CONCLUSIONS: A CE with a long operation time had more chance to explore the entire small bowel even in patients with suspected small bowel disease. PMID- 21033222 TI - Mast cells count and serum cytokine levels in patients with irritable bowel syndrome. AB - BACKGROUND/AIMS: Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder. Psychological factors and subtle histopathological changes have been implicated in IBS. In some studies, mast cell infiltration has been determined in colon mucosa of the patients with IBS. The aim of this study was to investigate the relationship between mast cell counts and cytokine levels and IBS. METHODOLOGY: 72 consecutive IBS patients fulfilling the Rome III criteria and 50 asymptomatic healthy controls underwent colonoscopic biopsy. 15 patients in diarrhea-predominant IBS group which were performed colonoscopy were made a biopsy from caecum, other 25 patients in diarrhea-predominant IBS and 32 patients in constipation predominant IBS were performed a biopsy from rectum. Additionally, serum cytokines were analysed in the patients with IBS and in control group. RESULTS: The results showed significantly increased mast cells in the IBS-diarrhea group compared to IBS-constipation and the control groups (p < 0.0001). The statistical analysis of the inflammatory cytokine data obtained in the present study showed significantly higher levels for the sIL-2 receptor in the IBS-diarrhea group compared to other groups. CONCLUSIONS: Histopathologic and laboratory data demonstrate low-grade mucosal inflammation in a subset of patients with IBS. Mast cells and cytokines may be related to the pathophysiologic mechanism of IBS. PMID- 21033223 TI - Colorectal GISTs: from presentation to survival. An analysis of 13 cases. AB - This papers is a retrospective analysis of all cases of colorectal GIST treated at our institution. Considering the increased interest in this pathology, in 2008, we recently established a unit supported by Novartis in our department to research and treat GIST. Since then, there was a dramatic increase in the referral of this type of tumor to our center. Before initiating our research group, we had the permission of the ethics committee and the medical directors to study and publish the analysis of our cases. Now, we have a cohort of 98 patients treated during the last 10 years and from that, we selected all cases of Colorectal GIST's. They numbered 13 cases. We performed an analysis of these cases from the presentation to the results of treatment. PMID- 21033224 TI - Experience of Altemeier's procedures for a complete rectal prolapse. AB - BACKGROUND/AIMS: Many patients with a complete rectal prolapse tend to be old. Therefore, surgeons tend to choose a surgical procedure associated with minimal stress. However, the recurrence rate is problematic. Altemeier's procedure causes minimal stress. This procedure is often selected for performing a complete rectal prolapse. Usually, a rectosigmoidectomy, is performed with levatoroplasty and anastomosis of the anal tube and the colon under spinal anesthesia. This procedure was applied for a complete rectal prolapse and the outcomes of this procedure were analyzed. METHODOLOGY: From 2000 August to 2006 January, 13 patients underwent this procedure. The patients ranged from 27 to 89 years of age (median 76 years). The length of the escaped enteric canal ranged from 7.0 to 20.0cm. RESULTS: All patients underwent the procedure under spinal anesthesia. The surgical time was 113 +/- 20 minutes. There were two postoperative complications which were both treated conservatively. One recurrent case was recognized. CONCLUSION: Altemeier's procedure was associated with a minimum of stress and the recurrence rate was low (7.6%). Because a complete rectal prolapse is caused by the fragility of the anal sphincter muscle and levator ani muscle, this procedure is considered to be effective and appropriate. PMID- 21033225 TI - Long-term complete response of unresectable liver metastases from colorectal cancer. AB - Recent advances in chemotherapy for metastatic colorectal cancer, such as fluorouracil -leucovorin, irinotecan, oxliplatin, and bevacizumab, have been demonstrated to achieve a high response rate. For most patients with unresectable liver metastases, however, chemotherapy is still not considered to provide a sufficient long-term disease-free survival without a surgical resection. We herein report two cases of a complete response for more than 8 years after having received treatment consisting of hepatic arterial infusion of fluorouracil and oral chemotherapy for unresectable liver metastases. The clinicopathological characteristics of these two cases were as follows: the number of liver metastases, 20, 11; the maximum size, 1.2 cm, 2.8 cm; the serum carcinoembryonic antigen level, 1.2 ng/ ml, 2.4 ng/ml. The following computed tomography scan revealed the liver metastases to have completely disappeared 7 months and 22 months after the treatment, respectively. It is speculated that a small size and a low level carcinoembryonic antigen may predict a good response to chemotherapy for unresectable liver metastases from colorectal cancer. PMID- 21033226 TI - Minimally invasive esophagectomy for cancer patients with low pulmonary function. AB - BACKGROUND/AIMS: The aim of the study is to assess postoperative pulmonary complications after minimally invasive esophagectomy for cancer patients with severe preoperative pulmonary dysfunction. METHODOLOGY: From 2004 to 2007, 37 patients underwent minimally invasive esophagectomy for esophageal cancer in our department. This procedure included hand-assisted thoracoscopic surgery and mediastinoscope-assisted transhiatal esophagectomy. The preoperative pulmonary function was evaluated using spirometry based on the Global Initiative for Chronic Obstructive Lung Disease system. Five of them had severe preoperative pulmonary dysfunction. RESULTS: Two of these patients developed aspiration pneumonia after the operation, which was successfully treated with antibiotics. The operating time, the incidence of postoperative pulmonary complication, and the duration of hospital stay were comparable for these five patients and those without preoperative pulmonary dysfunction. CONCLUSION: Minimally invasive esophagectomy can be safely performed for esophageal cancer patients with severe preoperative pulmonary dysfunction. PMID- 21033227 TI - Gastric emptying and electrogastrography in reflux esophagitis: results in patients showing endoscopically erosive esophagitis under proton pump inhibitor therapy. AB - BACKGROUND/AIMS: Dynamics of gastric emptying and motility are not fully understood in reflux esophagitis (RE) patients under proton pump inhibitor (PPI) therapy who have endoscopically diagnosed erosive esophagitis (EE). METHODOLOGY: Twenty patients with RE receiving 8 weeks of oral PPI (lansoprazole, 30 mg/day) administration and 17 healthy control subjects were enrolled. After a repeat endoscopy, gastric emptying and electrogastrography were performed. Patients were divided into two groups based on the Los Angeles classification after 8 weeks of PPI treatment--a response RE group (RG: patients with either non-EE or a two-rank improvement by an endoscopic grading system) and a non-response RE group (NRG: patients with EE and only one rank of improvement by endoscopic grading). RESULTS: The rates of RG and NRG were 12/20 and 8/20, respectively. A significantly delayed gastric emptying half-time (t1/2) prior to PPI therapy is shown in RE patients as compared to controls. The t1/2 in the NRG was delayed compared to RG. The frequencies of EGG in the fasting phase of the RE group were significantly lower than in controls. The rate of both fasting and nocturnal phase normogastria in the RE group was also markedly decreased compared to controls. There was no significant difference between the RG and NRG with regard to the frequencies of EGG waves. The rate of normogastria during the fasting phase in the NRG was lower than in the RG. CONCLUSIONS: Abnormalities of gastric motor function are persistently seen in the patients of non-responsive RE undergoing PPI therapy. PMID- 21033228 TI - Are there any functional differences of the enteric nervous system between jejunum and ileum in normal humans? AB - BACKGROUND/AIMS: Functional differences of the enteric nervous system (ENS) between the jejunum and ileum in humans are still unknown. To clarify the physiological differences of the ENS in the normal human jejunum and ileum, we investigated the enteric nerve responses on normal jejunum and normal ileum in vitro. METHODOLOGY: Twenty-two preparations of normal jejunum were taken from 22 patients with gastric cancer (14 men and 8 women, aged 43 to 65 years with a mean age of 49.0 years). Twenty preparations of normal ileum were also taken from 20 patients with right sided colonic cancer (15 men and 5 women, aged 40 to 63 years with a mean age of 50.9 years). A mechanographic technique was used to evaluate in vitro muscle responses to electrical stimulation (EFS) of adrenergic and cholinergic nerves before and after treatment with various autonomic nerve blockers. RESULTS: Responses to EFS before blockade of the adrenergic and cholinergic nerves; Muscle strips in jejunum and ileum demonstrated significant contraction reactions rather than relaxation reactions (p < 0.0001, p = 0.0001, respectively). In addition, jejunal muscle strips showed significant contraction reactions than those in ileal muscle strips (p = 0.0274). Responses to EFS after blockade of the adrenergic and cholinergic nerves; Jejunal muscle strips demonstrated relaxation reactions rather than contraction reactions by EFS (p = 0.0704). Ileal muscle strips significantly demonstrated relaxation reactions rather than contraction reactions by EFS (p < 0.0001). In addition, ileal muscle strips showed significant relaxation reactions more than those in jejunal muscle strips (p = 0.0451). Tetrodotoxin abolished the EFS responses in the muscle strips both jejunum and ileum. CONCLUSIONS: Cholinergic nerves are mainly involved in regulation of enteric nerves in the jejunum rather than the ileum. In contrast, the ileum was more strongly innervated by non-adrenergic noncholinergic inhibitory nerves than the jejunum. PMID- 21033229 TI - Factors contributing to the failure of argon plasma coagulation hemostasis in patients with nonvariceal upper gastrointestinal tract bleeding. AB - BACKGROUND/AIMS: Among endoscopic therapies, injection methods, thermal coagulation and mechanical devices are the major therapeutic modalities for upper gastrointestinal bleeding. Argon plasma coagulation (APC), non-contact electrocoagulation, is a procedure which involves thermal coagulation of tissue. In this study, our aim was to clarify the factors associated with APC treatment failure in patients with non-variceal gastrointestinal bleeding. METHODS: We followed up 58 non-variceal upper GI bleeding patients who received endoscopic treatment in our emergency department with APC to control bleeding from November 2006 to March 2008. Patients who received APC hemostasis were followed up to check for evidence of rebleeding by clinical symptoms and signs or drops of hemoglobulin during admission or after discharge. Rebleeding was defined as bleeding from the same lesions detected by repeat endoscopy. RESULTS: There were no significant differences between non-rebleeding and rebleeding patients in gender, age, presentation, initial systolic blood pressure, diastolic pressure, heart rate, hemoglobulin (pre-endoscopic and post-endoscopic treatment), BUN, creatinin or albumin. Patients with rebleeding had a lower platelet count than those withoutrebleeding(253.78 +/- 90.80 vs. 135.25 +/- 69.06, p = 0.020). In addition, patients with rebleeding had more comorbid disease (24/54 (44.4%) vs. 4/4 (100%), cirrhosis (3/54 (5.6%) vs. 3/4(75%), p = 0.002) and shock (4/54 (7.4%) and 2/4(50%) than those without rebleeding. There were no significant differences between non-rebleeding and rebleeding patients in ulcer size, location of ulcer, Forrest classification, blood transfusion, mean length of hospital stay, surgery or mortality. CONCLUSIONS: APC is an effective endoscopic therapy for non-variceal gastrointestinal bleeding. The presence of shock, low platelet count and cirrhosis may be associated with treatment failure of APC in non-variceal bleeding. PMID- 21033230 TI - The application of Montreal classification in different clinical and serological IBD subtypes. AB - BACKGROUND/AIMS: Inflammatory bowel disease (IBD) represents the heterogeneous group of disorders with a wide variety of clinical manifestations. The Montreal classification has been developed recently and its accuracy in categorizing of IBD phenotypes needs to be investigated. The aim of the study was to assess the usefulness of the Montreal classification compared to CAI and CDAI in various disease activity, serological and clinical manifestations of IBD. METHODOLOGY: The study was performed in 125 IBD patients: 71 patients with ulcerative colitis, 31 with Crohn's disease and 23 with IBD unclassified (indeterminate colitis). Disease activity and clinical course were assessed using Montreal classification, Clinical Activity Index and Crohn's Disease Activity Index. pANCA and ASCA were measured with ELISA, using widely used, commercial antibody panel (Cogent Diagnostics and Genesis Diagnostics and MedTek kits). RESULTS: No significant correlation has been found between pANCA/ASCA presence and disease activity using CAI and CDAI. ASCA and pANCA-/ASCA+ antibodies pattern had been detected more often in patients with Crohn's disease after surgery, with localization in small or small and large intestine, without perianal lesions and with early disease onset. CONCLUSIONS: Correlations between serotype and certain clinical phenotype are present, which could potentially be of value in the classification of patients particular treatment regimen. We have noticed that clinical course assessment using Montreal classification shows precisely real CD patients state. PMID- 21033231 TI - Where is the best skin incision for partial resection of the small intestine? AB - BACKGROUND/AIMS: For partial resection of the small intestine for benign disease such as Crohn's disease, a large incision has been placed in the mid-abdomen, for which ideal location and its length remain to be clarified. This study evaluated the validity of anthropometric placement of such an incision for partial resection of the small intestine. METHODOLOGY: Thirty consecutive patients with advanced rectal cancer (Age 30-82 {mean 60.1} years, 15 men and 15 women) who underwent anterior resection by open surgery between 2005 and 2006 were studied. The position of the viscera was projected on the anterior wall of the abdomen in relation to the umbilicus. RESULTS: The position of each viscera (Xcm, Ycm) was as follows; Duodenojejunal flexure (1.3 +/- 1.3, 9.4 +/- 2.1) and ileoceal valve (-7.3 +/- 1.0, -2.8 +/- 1.7). The small intestine which is not fixed to the retroperotoneum was located between the duodenojejunal flexure and the ileoceal valve. CONCLUSION: The ideal location of a small skin incision for small intestinal lesions is above the umbilicus for jejunal lesions, and below the umbilicus for ileal lesions. PMID- 21033232 TI - Testing for hepatitis B and C virus infection before upper gastrointestinal endoscopy: justification for dedicated endoscope and room for hepatitis patients. AB - BACKGROUND/AIMS: Endoscopic interventions have become a significant tool in the diagnosis and treatment of gastrointestinal disorders. In order to avoid transmission of associated diseases, cleaning and disinfection/sterilization procedures of endoscopes and accessories are crucial. Hepatitis B virus and Hepatitis C virus infections are among the most common viral infections globally and maintain their position as a serious public health problem. METHODOLOGY: One thousand patients visiting our gastroenterology department were diagnosed and, except for cirrhosis, were enrolled in this study. For patients with HBsAg and Anti-HCV positive, Aspartate Aminotransferase, Alanine Aminotransferase, hemogram and prothrombin time were examined and ultrasonography was performed. RESULTS: Five hundred and seventy three patients (57.3%) were female and 427 patients (42.7%) were male. Among 1000 patients in total, 39 patients were detected to have hepatitis (3.9%). Of these patients, 28 (2.8%) had HBsAg (+), 10 (1%) had Anti-HCV (+), 1 (0.1%) had both HBsAg (+) and Anti-HCV (+). CONCLUSIONS: It would be beneficial to include a determination of hepatitis serology of patients prior to endoscopy in daily practice. In addition, like dialysis machines, there is a need for further studies evaluating the cost effectiveness of using separate endoscopy devices allocated to groups of patients with HBV, HCV or to those who do not carry hepatitis. PMID- 21033233 TI - The efficacy of combined transarterial chemoembolization and 3-dimensional conformal radiotherapy for hepatocellular carcinoma with main portal vein thrombosis. AB - BACKGROUND/AIMS: The goal of this study was to evaluate the efficacy of combined therapy with TAE and 3-dimensional conformal radiotherapy (3D-CRT) for HCC with main portal vein thrombosis (MPVT). METHODOLOGY: We retrospectively reviewed the medical records of 18 patients who had an unresectable HCC with MPVT and underwent combined TAE and 3D-CRT. Treatment responses for the main tumor and the MPVT were assessed. In addition, patient survival and the prognostic factors associated with survival were analyzed. RESULTS: The overall survival for the 18 patients was 13.0 +/- 8.5 months. For the main tumor response, 8 patients were responders and 10 were non-responders. For the MPVT, an objective response was observed in 10 out of the 18 cases. The univariate analysis revealed that the pretreatment AFP level, presence of regional lymph node metastasis, main tumor response and the MPVT response were prognostic factors for survival; however, these factors failed to reach significance on the multivariate analysis. Most of the treatment-related complications were resolved within 4 weeks. No patient had clinical evidence of progressive hepatic insufficiency related to the treatment. CONCLUSIONS: Combined therapy with TAE and 3D-CRT was safe and effective for the treatment of HCC patients with MPVT and might provide a survival benefit. PMID- 21033234 TI - Preoperative segmentation of the liver, based on 3D CT images, facilitates laparoscopic anatomic hepatic resection for small nodular hepatocellular carcinoma in patients with cirrhosis. AB - BACKGROUND/AIMS: It is important to minimize surgical invasiveness in the therapy of patients with hepatocellular carcinoma (HCC) complicated with cirrhosis. Laparoscopic hepatectomy is feasible for such patients. However, most procedures undertaken at the present time are non-anatomic partial resection or limited resection, except for left hepatectomy and bisegmentectomy 2 and 3. Because anatomic hepatic resection for small HCC yielded more favorable results than non anatomic resection, we conducted laparoscopic anatomic hepatic resection as image navigated surgery by referring to portal 3D images. METHODOLOGY: Detailed descriptions of laparoscopic anatomic resection, such as segmentectomy and subsegmentectomy are presented. Preoperative 3D images clarified the anatomical relationships between HCC and its portal territory and enabled determination of the transection line. Laparoscopic anatomic resection was completed with mini laparotomy or -thoracotomy with equal success to the conventional procedure under an open approach. RESULTS: Five patients with primary HCC with cirrhosis underwent the above procedure between January 2008 and February 2009. There were 2 male and 3 female patients, with a median age of 74.4 (70-80) years. All procedures were successful, with no conversions to open surgery required. The median operation time was 251 min (range: 222-280 min), and the median estimated blood loss was 183 ml (range 50-320 ml). There was no surgical mortality and major morbidity. CONCLUSIONS: These procedures contributed reduced invasiveness, even for elderly patients with cirrhosis: low blood loss and no postoperative complication. Laparoscopic anatomic hepatic resection based on navigation of the portal 3D images might be useful not only to facilitate minimally invasive surgery but also to improve the therapeutic efficacy. PMID- 21033235 TI - Single orifice vein reconstruction in left liver plus caudate lobe graft. AB - BACKGROUND/AIMS: We describe the innovative techniques with single orifice vein reconstruction for the complete venous drainage in the left liver plus caudate lobe graft. METHODOLOGY: Eight left liver plus caudate lobe grafts used for living donor adult liver transplantation were reviewed. A wide and single venous orifice was created by gathering the left, middle or its tributaries, and/or short hepatic vein using a patch vein graft or a conduit vein graft. This single, newly-created orifice was then anastomosed to the common trunk created in the recipient's hepatic veins. RESULTS: Of 8 liver grafts, six included the middle hepatic vein trunk. Another two included only the middle hepatic vein tributaries. Significantly-sized short hepatic veins were preserved in 4 grafts and were connected with the major hepatic veins or tributaries of the middle hepatic vein to make a single orifice using a conduit vein graft. For remaining 4 grafts without significantly-sized short hepatic veins, two adjacent hepatic vein trunks (left and middle hepatic veins) were simply connected together. To enlarge the common orifice of the hepatic veins, the patch vein grafts were further attached. Hepatic vein waveforms of all grafts showed the biphasic or triphasic pattern and the graft congestion was not observed immediately after venoplasty. No graft was lost due to hepatic venous outflow block with the mean follow-up of 15 months. CONCLUSIONS: The short-term results of our technique were satisfactory. The present technique can simplify graft-to-recipient hepatic vein reconstruction without unfavorable tension on the anastomosis. PMID- 21033236 TI - UCSF criteria by pre-transplant radiologic study can not assure similar post transplant results of hepatocellular carcinoma within Milan criteria. AB - The recurrence of hepatocellular carcinoma (HCC) after transplantation is the main limitation of liver transplantation. Therefore, several selection criteria for liver transplantation in HCC patients have been established. The objective of this study was to verify the clinical validity of selection criteria evaluated by pre-transplant radiologic imaging study. Sixty-nine participants were enrolled for this study between September 2005 and May 2007. We analyzed the post transplant survival and recurrence rate using radiologic selection criteria and other clinical factors. Grouping by pretransplant criteria for liver transplantation, 16 recipients (23.2%) were above Milan criteria and 7 recipients (10.1%) were above UCSF criteria. Nine recipients (13.0%) were grouped as above Milan/below UCSF. The recipients who met Milan showed 85.8% 1-year survival rates, which was comparable to that of non-HCC (91.6%) (p = 0.767). During the post-transplant follow-up period (1-52 months, 14.81 +/- 12.0 months), 16 recurrences (23.2%) were diagnosed. The 1-year recurrence-free survival rate of recipients who met the Milan criteria was 78.6%, and those that did not meet these criteria was 22.7% (p < 0.0001). With regard to UCSF criteria, these percentages were 72.0% and 14.2%, respectively (p < 0.0001). According to a combined grouping, the 1-year recurrence-free survival rate was 25.4% in the above Milan/below UCSF group. There were significant differences among each of the groups (overall p < 0.0001). The application of UCSF criteria that are defined by pre-transplant radiologic findings as patient selection criteria for liver transplantation is limited. PMID- 21033237 TI - Thyroid dysfunction in antiviral therapy of chronic hepatitis C. AB - BACKGROUND/AIMS: Thyroid disorders are common dysfunctions during HCV infection and IFN-therapy. The aim of the study was to evaluate the general risk of thyroid disorders' development in chronic HCV-infected patients and their possible relationship with HCV genotype, type of used IFN-alpha and viral response. METHODOLOGY: A study was performed in 89 patients with chronic hepatitis C (57 males, 32 females) and 25 healthy subjects. All HCV-infected patients were treated by IFN-alpha and RBV for a period depending on the HCV genotype. Hematological parameters, liver and thyroid function tests were analyzed. Serum Tpo-Ab and TG-Ab were detected by semiquantitative ELISA. In statistical analyses U Mann-Whitney and Spearman correlation tests were used. Ap value < 0.05 was considered significant. RESULTS: Twelve (13.5%) CHC patients developed thyroid disorders during IFN-alpha therapy. Thyroid disorders were more often detected in females, in 3a-genotype-infection and in patients treated with natural leukocyte IFN-alpha. Seven (7.6%) Tpo-Ab and/or TG-Ab positive patients were noticed. Four of them (57.1%) developed hypothyroidism during IFN-alpha therapy. CONCLUSION: This study demonstrated low effect of IFN-alpha therapy on thyroid disorders development and on TPO-Ab and TG-Ab serum level in chronic HCV-infected patients. PMID- 21033238 TI - The impact of steatosis on liver stiffness measurement in patients with chronic hepatitis B. AB - BACKGROUND/AIMS: Recently, several studies have indicated that liver stiffness measurement (LSM) using FibroScan accurately predicts liver fibrosis. This study investigated the impact of steatosis on LSM in patients with chronic hepatitis B (CHB). METHODOLOGY: The study prospectively enrolled 162 patients (106 men and 56 women) with CHB who underwent both a liver biopsy and LSM between January 2005 and June 2008. We examined the overall univariate correlation between steatosis and LSM value and also performed a multivariate regression analysis to identify independent variables influencing LSM values. RESULTS: The mean age of the patients was 44.4 years and the mean body mass index was 23.3 +/- 2.8kg/m2. The fibrosis stage ranged from F1 to F4 in 16 patients (9.9%), 37 (22.8%), 17 (10.5%) and 92 (56.8%), respectively. Steatosis was S0 in 128 patients (79.0%), S1 in 28 (17.3%), S2 in 6 (3.7%) and S3 in none. No overall significant correlation was noted between LSM value and steatosis (r = 0.023, p = 0.770). In the multivariate linear regression analysis, only fibrosis stage showed statistical significance (r = 0.268, p < 0.001), while steatosis did not (r = 0.013, p = 0.841). CONCLUSIONS: Our findings suggest that mild to moderate steatosis does not have a significant impact on LSM values in patients with CHB. PMID- 21033239 TI - Does long-term ventilation with PEEP > or = 10mbar influence graft-function in patients following liver transplantation? AB - BACKGROUND/AIMS: Long-term positive end-expiratory pressure (PEEP) ventilation, particular with PEEP up to 15 mbar may impair graft-function in liver transplant (LT) patients. The aim of our study was to evaluate the impact of long-term high PEEP (at least 48 hours) on liver graft function. We retrospectively reviewed the records of 50 patients, who required artificial ventilation for at least 1 week with a PEEP level > or = 10mbar due to pulmonary complication caused mainly by sepsis (n = 19), pneumonia (n = 7) and lung edema associated with reperfusion syndrome or primary non-function of the graft (n = 13). Patients who required a PEEP > or = 10mbar within the first two days after transplantation (group A, n = 23) showed significant decrease of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and bilirubin on day 3 and day 7 after initiation of high PEEP, whereas prothrombin time (PT) significantly increased on day 7. Group B (patients ventilated with PEEP > or = 10mbar after more than 2 days after transplantation, n = 27) showed a significant decrease of bilirubine and a significantly increase of PT on day 7. CONCLUSION: Long-term ventilation with PEEP levels of at least 10mbar does not harm graft function in patients following LT. PMID- 21033240 TI - Inadequate nutritional intake and protein-energy malnutrition involved in acute and chronic viral hepatitis Chinese patients especially in cirrhosis patients. AB - BACKGROUND/AIMS: Early detection and treatment of protein-energy malnutrition have great clinical significance in patients with liver disease. The aim of study was to evaluate the nutritional status and determine the prevalence of malnutrition in acute and chronic viral hepatitis in Chinese patients, especially in cirrhosis patients. METHODOLOGY: A total of 315 patients were enrolled in this project, 20 patients with acute viral hepatitis, 142 patients with chronic viral hepatitis and 153 patients with posthepatitic liver cirrhosis. Recorded dietary nutrititional intakes and evaluated nutitional status by subjective global assessment, anthropometrics and biochemical data were carried out consecutively. RESULTS: According to the Chinese Dietary Recommended Nutrient Intakes based on sex and age, 73.0% +/- 29.66% of cirrhotic patients, 68.10% +/- 28.65% of chronic hepatitis patients, and 63.38% +/- 29.24% of acute hepatitis patients had deficient energy and nutrients intake. The prevalence of malnutrition was higher in the cirrhotic group as compared with the chronic or acute hepatitis groups according to the subjective global assessment, measured as triceps skinfold thickness in females, mid-upper arm muscle circumference in both male and female patients, albumin, prealbumin, hemoglobin, and serum transferrin (p < 0.05, respectively). CONCLUSIONS: This study demonstrated that Chinese patients with acute and chronic viral hepatitis and liver cirrhosis had inadequate energy and nutritional intake. Protein-energy malnutrition was more severe in cirrhotic patients, indicating a need for early enteral and perenteral treatment. PMID- 21033242 TI - Salvage surgery for uncontrollable hepatocellular carcinoma treated with repeated non-surgical therapies. AB - BACKGROUND/AIMS: Some hepatocellular carcinoma (HCC) cases undergo surgery because tumor progression cannot be controlled by various non-surgical therapies. This retrospective study sought to clarify the clinicopathologic features of such HCC cases. METHODOLOGY: Among cases with solitary small HCCs (< or = 3.0cm at the time of detection), the clinicopathologic features of 7 patients who had undergone hepatectomy after various non-surgical therapies (Salvage (S) group) were analyzed and compared with those of 30 patients who received hepatectomy as the initial treatment (Control (C) group). RESULTS: In S group, the serum alpha fetoprotein level was higher (p = 0.045) and macroscopic ductal invasion was more common (p = 0.028) at the time of the operation. Lobectomy was more commonly performed (p = 0.034) and curability B (No residual cancer, but Stage III or IV) was more frequent (p = 0.011). Other organ recurrence was more common (p = 0.0044). The survival time after the initial treatment (post-initial treatment survival) was worse (p = 0.028). Univariate analyses revealed that those with maximum tumor sizes of > 3.0 cm at the time of the operation were significantly worse compared with the other patients (p = 0.012). CONCLUSIONS: The timing for changing from a non-surgical treatment to a surgical treatment is important. PMID- 21033241 TI - Management of fungal colonization and infection after living donor liver transplantation. AB - BACKGROUND/AIMS: Control of infection is important in liver transplant patients under immunosuppressive conditions. In particular, invasive fungal infection is often fatal if diagnosis and therapy are delayed. The aim of this study was to analyze the incidence of fungal colonization and infection after living donor liver transplantation (LDLT). METHODOLOGY: Retrospective analysis was performed with 60 consecutive adult recipients of LDLT. RESULTS: Fungi were isolated from specimens of 16 (26.7%) patients after LDLT. All the fungi were Candida species. One patient for whom Candida species were isolated in ascites and blood was complicated with systemic methicillin-resistant Staphylococcus aureus and cytomegalovirus infection. In the univariate analysis, fungal carriage before surgery (p = 0.01) was associated with fungal isolation after LDLT. In the multivariate analysis, fungal carriage was found to be an independent predictor of fungal isolation (odds ratio: 15.7, p = 0.03). Of the 60 recipients, 16 (26.7%) showed serum levels of beta-D glucan above 60 pg/ml after surgery. Among these, 4 died and were all complicated with severe bacterial infection. CONCLUSION: Preoperative fungal carriage was associated with fungal isolation after LDLT. If fungal infection was suspected after LDLT, along with treatment against fungi, control of complicated infections with other pathogens to be simultaneously considered. PMID- 21033243 TI - Clinical significance of occult hepatitis B virus infection: illustrative cases. AB - Occult HBV infection (OBI) is an increasingly reported form of hepatitis B virus (HBV) infection, With the current knowledge, in immunocompetent individuals, OBI is mainly a diagnostic challenge and has a very low probability of transfusion risk, controversial risk of liver disease or hepatocellular carcinoma, etc. In immunosuppressed individuals, however, reactivation of OBI is a real concern even today. There are many controversies about the management of such cases, including anti-HBc and/or alanine aminotransferase monitoring, HBV DNA monitoring, vaccination or pre-emptive nucleoside analogs. We present here four OBI cases which reveal the difficulties in the diagnosis and management of OBI and include a discussion upon current literature. PMID- 21033244 TI - Significance of increased serum GGTP levels in HCC patients. AB - A large dataset of patients with biopsy-proven and unresectable HCC who were prospectively followed from diagnosis till death, was examined for the prognostic significance of serum GGTP levels. Their survival-ordered baseline clinical parameter data was examined. Two cohorts of patients with both low AFP and bilirubin levels were identified, who had serum GGTP levels with an increasing trend with increasing AFP levels. The survival of these patients also decreased as their GGTP levels trended up, as did their tumor masses. By contrast, in patients with elevated serum AFP levels, the GGTP trends were less informative, although patients with the highest AFP levels had a worse prognosis if their GGTP levels were simultaneously elevated. The results suggest that following trends in serum GGTP levels, in the context of specific ranges of AFP and bilirubin levels, might be useful in diagnosis of small HCCs. PMID- 21033245 TI - Postconditioning prevents ischemia/reperfusion injury in rat liver transplantation. AB - BACKGROUND/AIMS: Ischemic postconditioning (Postcon) is a phenomenon that intermittent interruptions of blood flow in the early phase of reperfusion can protect organ against ischemia/ reperfusion (I/R) injury. The potential application of postconditioning to liver is not available. In the present study, we investigated the effects of Postcon in liver I/R injury in rat liver transplantation models. METHODOLOGY: Adult male Sprague-Dawley rats were randomly allocated to three groups including sham group without I/R, I/R group with 24h cold ischemic donor liver before orthotopic liver transplantation, and Postcon group treated the same as I/R group and 6 cycles of 60s ischemia and 60s reperfusion at the onset of reperfusion. Peripheral blood samples were collected after reperfusion. Serum transaminases level, plasma cytokines concentration, histopathology, liver tissues malondialdehyde (MDA) level and superoxide dismutase (SOD) activity were measured. The heme oxygenase-1 (HO-1) expression levels of liver were evaluated. RESULTS: Serum transaminases level and plasma cytokines concentration significantly decreased in Postcon group as compared to I/R group. Postcon treatment reduced MDA production and increased SOD activity compared with the I/R group. The HO-1 expression levels of liver were significantly higher in Postcon rats than in the I/R group at the end of reperfusion. CONCLUSIONS: These results indicate that Post-con ameliorates liver I/R injury. This protective effect is likely mediated by up-regulation of HO-1 expression. PMID- 21033246 TI - Very low density lipoprotein receptor subtype II silencing by RNA interference inhibits cell proliferation in hepatoma cell lines. AB - Very low density lipoprotein receptor (VLDLR) belongs to the low density lipoprotein receptor family, it is divided into two subtypes according to forms with an absence (type II) or a presence (type I) of the O-linked sugar domain. VLDLR have been detected in kinds of cancers so far; however, the subtype of VLDLR in hepatocellular carcinoma (HCC) tissues and hepatoma cell lines has yet to be reported. We detected the VLDLR expression in 39 cases of hepatocellular carcinoma and in three kinds of hepatoma cell lines: HepG2, HBV transfected HepG2.2.15, SMMC-7721 and normal human fetal liver cell line LO2 using RT-PCR and western blotting. The results showed that both type I and type II VLDLR were detected in HCC tissues and hepatoma cell lines, and the type II VLDLR expression was significantly higher than that of type I in cell lines. We inhibited the type II VLDLR expression by shRNA-mediated RNA interference in HepG2, SMMC-7721 cell and then subsequently found the cell proliferation slowed down. The cyclinD1 expression confirmed the cell cycle was arrested at the G0/G1 phase, suggesting that inhibiting the type II VLDLR expression may have a positive impact on carcinogenesis of HCC. PMID- 21033248 TI - Hepatocyte infusions improve the results of liver transplantation in rats. AB - BACKGROUND/AIMS: The results of liver transplantation were influenced by miscellaneous factors. The aim was the notion that hepatocyte infusions might improve results of liver transplantation in rats. METHODOLOGY: Survival, serum analytes, FasL production, and histologic degree of rejection of transplanted rats pretreated with hepatocyte infusions (Hepatocyte) was compared to that of rats pretreated with either bone marrow cell infusions (Marrow) or saline infusions (Control). RESULTS: Hepatocyte rats had longer median survivals, less biochemical evidence of liver damage, more albumin production, a lower degree of histologic rejection, and increased FasL production than did either Marrow or Control rats (p < 0.05 for each analysis), which did not differ from one another (p > 0.05 for each analysis). CONCLUSIONS: Hepatocyte infusions improve the results of liver transplantation in rats. PMID- 21033247 TI - The effect of differentiating and apoptotic agents on notch signalling pathway in hepatoblastoma. AB - BACKGROUND/AIMS: Notch expression is not yet determined in hepatoblastoma. In this study the effect of chemotherapeutics (cisplatin, doxorubicin, cytosin arabinoside); differentiating agent (13 cis-retinoic acid) and apoptotic agents (5-aza-2'-deoxycytidine, arsenic trioxide) on notch expression in hepatoblastoma were evaluated. METHODOLOGY: After HepG2 cell line was cultured and the agents and their combinations were applied for 24 hour in pre-optimized 50% lethal doses, RNA isolation and cDNA converting, expression of 84 custom array genes of notch signaling pathway (SABiosciences, PAT059F-24) was determined by Real Time PCR. The methylation status of 6 genes that showed more than 5 fold changes compared with control group were explored by Methylation qPCR Assay. High expressed genes are HDAC1, NFKB1, CHUK, CDKN1A, and CBL. Low expressed genes are DLL1, CD44, FZD2, GLI1, IL17B, LMO2, NOTCH1, LOR, PAX5, PT-CRA, SH2D1A, and WISP1. The genes searched for methylation (DLL1, HEY1, DTX1, HDAC1, NOTCH2 and JAG1) were not found to be related with methylation. RESULTS: The high expressed genes are related with cell proliferation. The main signaling genes that are closed to notch in signaling pathway are low expressed in hepatoblastoma. The agents do not show prominent effect of gene expression in many genes and methylation is not the reason of expression changes. The use of retinoic acid in the control of minimal residual disease of hepatoblastoma should be discussed. 5 aza "cytidin" the demethylating agent is not advised in treatment according to our results. CONCLUSION: Cisplatin as main chemotherapeutic agent treatment is shown to change gene expression levels in notch signalling pathway in hepatoblastoma. PMID- 21033250 TI - The relationship between HBV-DNA level and histology in patients with naive chronic HBV infection. AB - BACKGROUND: In patients with chronic hepatitis B (CHB) infection, precise definition of the hepatic fibrosis stage is the most important parameter to assess the risk of disease progression. Correlation between the prognosis of the CHB and the level of hepatitis-B virus DNA (HBV-DNA) is well considered in recent years. AIMS: The aim of this study is to investigate the relationship between serum HBV-DNA level and histology of the liver. We also wanted to determine a threshold level of HBV-DNA for differentiation of low and high risk patients for progression. METHODS: Two-hundred-fifty-nine patients with serum HBV-DNA level > 2000 copies/mL, determined by polymerase chain reaction (PCR), and biopsy proven naive CHB infection were evaluated. Liver biopsies were evaluated histopathologically according to the Ishak scoring system. Laboratory values such as aspartate aminotransferase (AST), alanine aminotransferase ratio (ALT) were tested every 3 months and the highest value of each patient was evaluated. RESULTS: Mean age was 40 +/- 11 and 60% (155/259) of the patients were male. Mean laboratory values were as follows: AST: 52 +/- 46 U/L, ALT: 93 +/- 133 U/L, PLT: 224 +/- 60 1093)/l HBV DNA: 5.9 +/- 1.5 log copies/mL. In histological evaluation, mean inflammatory score was 4.34 +/- 2.72 and fibrosis score was 1.38 +/- 1.46. The fibrosis score was 0 or 1 in 63.3% (164/259) of the patients. The relationship between HBV-DNA level and histologic grade/stage was investigated and 15.000 copies/mL HBV DNA level was found as the threshold level to describe the activity of the disease. Fibrosis score was < 2 and/or grade < or = 5 in the patients who have HBV-DNA value below that level. CONCLUSION: In patients who have serum HBV-DNA level < or = 15000/copies/mL, histological activity was almost always low, and it seems that these patients do not need a liver biopsy regardless of hepatitis-B-e antigen (HBeAg) status. PMID- 21033249 TI - Gray-scale ultrasonography shows serial changes of the congestive area after living donor liver transplantation using right lobe graft. AB - BACKGROUND/AIMS: Hepatic venous congestion after living donor liver transplantation using right lobe graft produces various abnormalities on ultrasonography. Doppler sonography can reveal reversal of the portal flow direction in patients with acute and severe venous congestion and can show the presence of a functional intrahepatic anastomosis between the hepatic vein tributaries during the follow-up period in those people with improved congestion. However, few abnormal findings have so far been observed using gray-scale ultrasonography. METHODOLOGY: Thirteen patients who underwent living-donor liver transplantation using right lobe graft enrolled in this study. Postoperative ultrasonography was performed during the first 14 days after surgery. The serial changes of the congestive area indicated by gray-scale ultrasonography were quantitatively and qualitatively analyzed. RESULTS: Gray-scale ultrasonography showed the congestive areas as hyperechoic lesion in comparison to normal hepatic parenchyma. Congestive areas were seen in 4 patients in the early postoperative period (1-3 postoperative days). The acoustic intensity was higher in the congestive areas than in non-congestive areas (19.7 +/- 1.6 vs. 9.7 +/- 1.8 dB, respectively) in the early postoperative period. However, there was no difference between the congestive and non-congestive areas (21.3 +/- 5.0 vs. 19.8 +/- 2.6 dB, respectively) in the late postoperative period (8-14 postoperative days). Interestingly, the acoustic intensity in the congestive area in the early postoperative period was similar to that in the non-congestive area in the late postoperative period (19.7 +/- 1.6 vs. 19.8 +/- 2.6 dB, respectively). In nine patients who had no congestive area, acoustic intensity was similar throughout the postoperative period. CONCLUSIONS: Congestive areas can be seen in gray-scale ultrasonography. A congestive area may spread to a non-congestive area in patients whose congestive area can be seen on gray-scale ultrasonography in the early postoperative period. PMID- 21033251 TI - Mammalian target of rapamycin as a novel target in the treatment of hepatocellular carcinoma. AB - Several studies have discovered that PI3K/Akt/ mammalian target of rapamycin (mTOR) pathway played an important role in the development of cancer. In this study, we examined the effects of antisense pEGFP-C1-mTOR on cell proliferation, apoptosis and migration of human hepatocellular carcinoma cell lines, HepG2 and SMMC7721 in vitro. We also observed the expression of mTOR and Akt by using RT PCR and western blot. Our results showed that treatment of cells with antisense pEGFP-C1-mTOR could induce human hepatocellular carcinoma cells' growth inhibition, apoptosis and weaken the migration activity. And we observed that the expression of mTOR was significantly decreased in the cells treated with antisense pEGFP-C1-mTOR and interestingly we discovered that the phosphorylation AKT expression was slightly increased. It indicated that there existed a negative feedback effect which might decrease the therapeutic effects of antisense pEGFP C1-mTOR. Therefore, we conceive that targeting to inhibit the expression of mTOR in combination with AKT inactivate may increase clinical effectiveness in hepatocellular carcinoma's treatment. PMID- 21033252 TI - BC047440 overexpression is a risk factor for tumor invasion and poor prognosis in hepatocellular carcinoma. AB - BACKGROUND/AIMS: The aim of this study was to investigate the relationship between a new tumor-relative protein (BC047440) expression and clinic pathological parameters of hepatocellular carcinoma (HCC), and to evaluate the prognostic value of BC047440 for HCC patients. METHODS: Following the prokaryotic expression and polyclonal antibodies generation of BC047440, two methods, including western blot and immunohistochemical staining were employed to detect BC047440 expression in 68 HCC specimens. The correlation between BC047440 expression and clinicopathologic outcome, and prognostic value of BC047440 for HCC patients were analyzed. RESULTS: The polyclonal antibodies could effectively recognize endogenous BC047440 in HCC tissues. Western blot and immunohistochemical staining revealed that the expression of BC047440 protein was higher in HCCs than that in adjacent tissues and normal liver tissues. Statistical analysis showed that there was a good correlation between BC047440 expression and tumor size and invasion of HCC. HCC patients with BC047440 positive expression showed a significantly poor prognosis than those with BC047440-negative expression. CONCLUSIONS: BC047440 has a regulatory function in progress of HCC and it may become a helpful indicator in handling HCC treatment and judging invasion. PMID- 21033253 TI - Tumour necrosis factor 308 polymorphisms and hepatocellular carcinoma risk: a meta-analysis. AB - BACKGROUND/AIMS: To investigate the association of the common polymorphisms comprehensively defining the genetic variability of the TNFA-308G > A with HCC risk. METHODOLOGY: We performed a meta-analysis of 9 published studies that included 1362 cancer cases and 2426 controls. We used random-effect (RE) or fixed effect (FE) odds ratios (ORs) and 95% confidence intervals (CIs) according to the studies' heterogeneity to assess the strength of the associations. RESULTS: The overall results suggested that the TNFA-308 AA and AG variant genotypes were associated with a significantly increased risk of HCC in different genetic models (homozygote comparison: OR = 2.51,95% CI: 1.11-5.67, p heterogeneity = 0.905; heterozygote comparison: OR = 1.58, 95% CI: 1.00-2.50, p heterogeneity = 0.001; dominant model comparison: OR = 1.59, 95% CI: 1.00-2.53, p heterogeneity = 0.000; recessive model comparison: OR = 2.27, 95% CI: 1.01-5.12, p heterogeneity = 0.962; complete overdominant model comparison: OR = 1.57, 95% CI: 1.00-2.45. P heterogeneity = 0.001; and allele comparison: OR = 1.52, 95% CI: 1.01-2.28, p heterogeneity = 0.002. There was at some extent heterogeneity when analyses were performed in some models, and there was no publication bias. CONCLUSIONS: This meta-analysis supported that the TNFA-308 A allele is a risk factor for HCC development. PMID- 21033254 TI - Biliary complications after liver transplantation--523 consecutive cases in two centers. AB - BACKGROUND/AIMS: Despite various surgical techniques, biliary tract complications (BC) remain a major source of morbidity after liver transplantation (LT). METHODOLOGY: Between April 2000 and November 2008, 523 LTs in 487 recipients (36 re transplantations) were performed as follows: 402 whole deceased donor graft LTs, and 121 partial liver transplantation: 75 living donor liver transplantation, 42 split liver transplantation, and 4 reduced size liver transplantation. RESULTS: Mean follow-up period was 935 days (range 1-3174), 1, 3 and 5-year survival rates were 78.7% 74.2% and 74.2%, respectively. One hundred twenty seven patients--from 487 (26%), developed (after 135 LT) 150 singular BC (in total were 181 BC). Sixty four (of 85) bile leaks (75.29%) were early BC, while 53 (of 63) stenosis (84.1%) were late BC. BC does not influenced significantly patients and graft survival (p > 0.6). From 102 deaths, 8 were due to BC (1.6%) and in only 14 (2.67%) graft loss of 523 LT BC had the main role. Multiple ducts, multiple biliary anastomosis and RYHJ determine BC if compared to a single duct graft. Moreover, ductoplasty, graft type and HAT were independent risk factors. CONCLUSION: Biliary complications are common after LT but are rarely an isolated cause of death. PMID- 21033255 TI - Cost-effectiveness of peginterferon alpha-2a and peginterferon alpha-2b combination regimens in genotype-1 naive patients with chronic hepatitis C. AB - BACKGROUND/AIMS: Pegylated interferons (Peg-IFNs) with ribavirin represent the standard treatment in chronic C viral hepatitis in Romania. Primary aim was to evaluate the cost-effectiveness of Peg-IFN alpha-2a plus ribavirin versus IFN alpha-2b plus ribavirin in genotype-1 patients in Romanian setting. The second end point was to make an indirect comparison of the cost-effectiveness of combination therapy of the two Peg-IFNs. METHODOLOGY: Published clinical data on sustained virological response rates (SVR) and early virological response rates (EVR) from more recent published studies were used for both combination therapies. A Markov model with seven health states was built. The reference patient was a 45-year-old male with chronic non-cirrhotic liver disease due to chronic HCV infection. Time horizon is patient lifetime. Published data on the natural history of hepatitis C, local mortality data, published utilities and local expertise were used for assessment of local procedures, resources used and costs. The perspective is that of the National Health Insurance Agency (NHIA). RESULTS: The incremental cost of treatment with Peg-IFN alpha-2a plus ribavirin is 19,056 Rol per LY gained and 27,175 Rol per QALY gained. A one-way sensitivity analysis showed that results are sensitive to the discount rate used, but they still are highly cost-effective. The indirect comparison of cost-effectiveness of Peg-IFNs combination therapies over IFN alpha-2b showed superiority of Peg-IFN alpha-2a and ribavirin therapy. CONCLUSION: This study demonstrates a higher cost effectiveness of the current state-of-the art treatment with Peg-IFN alpha-2a with ribavirin over the standard IFN and ribavirin combination. Although a slight superiority of Peg-IFN alpha-2a over Peg-IFN alpha-2b combined regimen was shown in Romanian setting in terms of LYs and QALYs gained, there are no significant differences in cost-effectiveness of the two therapies. PMID- 21033256 TI - Gemcitabine in arterial injection chemotherapy for pancreatic cancer does not cause catheter obstruction or any other complication. AB - BACKGROUND/AIMS: Intra-arterial injection therapy is performed to ensure more localized administration; however, this approach has led to more cases of catheter obstruction during the course of treatment for pancreatic cancer than in any other type of cancer. Therefore, the purpose of this study was to verify the resistance of catheters to gemcitabine. METHODOLOGY: The catheters were prepared by injecting gemcitabine into the lumen, which was subsequently closed by clipping both ends. After incubation, the gemcitabine in the lumen of the catheter was removed, the breaking strength was measured by pulling 1 side of the catheter at a speed of 500 mm/min to test the tensile strength. To verify the surface of the lumen, the lumen was observed with an electron microscope. RESULTS: Soaking the lumen revealed no significant differences in breaking strength due to abusive treatment conditions. Electron microscopy revealed residual microscopic amounts of gemcitabine in the lumen but with no marked deterioration or alteration in the quality of the tube surface. CONCLUSIONS: Gemcitabine had no chemical effect on the intra-arterial injection catheter. It is possible that a thrombotic tendency in pancreatic cancer patients may be responsible for the high frequency of catheter occlusion in patients with this disease. PMID- 21033257 TI - Biliary diversion Q-shape reconstruction after pancreaticoduodenectomy: Chang's reconstruction. AB - BACKGROUND/AIMS: This is a simple and easy reconstruction method designed for safely performing a pancreaticoduodenectomy (PD), even when it is complicated by a leakage from pancreaticojejunostomy (PJ). METHODOLOGY: Five patients with periampullary malignancy underwent PD with biliary diversion Q-shaped reconstruction. An end-to-side anastomosed proximal jejunal loop (30 cm), divided by a gastrointestinal anastomosis (GIA) stapler at its top and reapproximated by intermittent serosal sutures, was used for a choledochojejunostomy and a PJ (fistulation, duct-to-mucosa, or end-to-side method) at each divided loop. Then gastrojejunostomy or duodenojejunostomy was made 30 cm distal to the jejunojejunostomy of the loop. RESULTS: The clinic courses were surprisingly uneventful. There was no mortality. One patient showed a minor pancreatic leakage, one pylorus-preserving patient experienced a 25-day delay in gastric emptying, and another patient required second operation for intra-abdominal bleeding from a tiny branch of the superior mesenteric artery. CONCLUSION: Biliary diversion Q-shaped PD is a safer reconstruction method for reducing lethal hemorrhagic crisis associated with PJ anastomotic leakage after PD. PMID- 21033258 TI - Secondary surgery subsequent to distal pancreatectomy. AB - BACKGROUND/AIMS: Early revision procedures after pancreatic head resection significantly increase mortality. Due to their complexity, secondary operations at a later stage rank amongst the most demanding surgical procedures. We sought to critically analyze indications and outcome from early revision and subsequent redo procedures following distal pancreatic resection (DPR). METHODOLOGY: During a 5-year period 53 subsequent patients undergoing DPR were identified from a pancreatic resection database and analyzed regarding indication for and outcome of early revision and late redo procedures. RESULTS: Six patients (11%) underwent early revision procedures during the same hospital stay. Indications were peritonitis (n = 3), intraabdominal hemorrhage (n = 2) and oncologic re-resection (n = 1). Four patients (7.6%) were readmitted after 192 days (d) on average (range 53 - 538d) and underwent subsequent redo surgery due to occurrence of metastases in 2 cases, and insufficiency of an ascendo-rectostomy and adhesive ileus. Hospital stay and mortality were significantly increased after early revision surgery (40d vs. 18d; 33% vs. 0%). Splenectomy during DPR was carried out in all patients requiring early operative reintervention, compared to 63% in patients without secondary surgery (p < 0.07). CONCLUSIONS: Early revision surgery following DPR increases postoperative mortality and length of hospital stay. Risk factors were complex injuries (e.g. gun shot wound), concomitant portal hypertension with collateral circulation and splenectomy. Subsequent redo surgery following DPR was performed on average within 7 month following the index operation without mortality and with comparable morbidity. Indications were recurrent malignant disease and complications of the intestine. PMID- 21033259 TI - Incidence of pancreatic carcinoma in patients with chronic pancreatitis. AB - BACKGROUND/AIMS: Pancreatic carcinoma belongs to the area of conditions with late diagnosis and there is no effective screening method. One possible approach to diagnosing so called early adenocarcinoma, therefore, lies in the identification and systematic examination of individuals in risk for this condition. METHODOLOGY: Between 1992 and 2005 we systematically observed 223 individuals diagnosed with chronic pancreatitis. In this 14-year period we performed classical biochemical tests, endoscopic ultrasound, CT scans and ERCP, we asked about the number of cigarettes smoked per year and classified individuals consuming regularly more than 80 g of alcohol per day for 5 years for men and 50 g of alcohol per day for 5 years for women as having the alcoholic form of chronic pancreatitis. The remaining patients were classified according to TIGARO classification. RESULTS: Alcohol-related etiology was detected in 73.1% of patients, 21.5% had the chronic obstructive form and only 5.4% were classified as idiopathic pancreatitis. Pancreatic carcinoma was detected in 13 patients with chronic pancreatitis (5.8%), three patients were diagnosed with gastric carcinoma and one with esophageal carcinoma. Pancreatic malignancy developed mainly in patients with the alcoholic form of pancreatitis (4.5%). In the 14 year period 11 subjects died, out of which eight cases were related to pancreatic carcinoma. CONCLUSION: Pancreatic and extra-pancreatic cancer localized in the gastrointestinal tract are among the serious complications of chronic nonhereditary pancreatitis. Systematic observation of patients with chronic pancreatitis must be performed with the aim of early diagnosis of pancreatic, but not only pancreatic malignancies. PMID- 21033260 TI - Klatskin-mimicking lesions--a case series and literature review. AB - Obstruction of the hepatic hilum in patients without prior surgery is generally due to hilar adenocarcinoma (Klatskin tumor). However, not all the hilar strictures are malignant. Although uncommon, benign strictures of the proximal bile duct should be taken into consideration in differential diagnosis of Klatskin tumors, since the incidence could reach up to 25% of patients with presumed Klatskin tumor diagnosis. This group of benign proximal bile duct strictures (Klatskin-mimicking lesions) is usually represented by segmental fibrosis and non-specific chronic inflammation. The clinical and imaging features can not differentiate between benign and malignant strictures. Herein, we present a case series of three patients with benign proximal bile duct strictures (representing 4.1% of 73 patients resected with presumptive preoperative diagnosis of Klatskin tumor) and literature review. There are presented the clinical and biochemical features, imaging preoperative workup, surgical treatment and histological analysis of the specimen, along with postoperative outcome. For benign strictures of the hilum limited resections are curative. However, despite new diagnosis tools developed in the last years, patients with hilar obstructions still require unnecessary extensive resections due to impossibility of excluding the malignancy. In all cases of proximal bile duct obstruction presumed malignant, they should be managed accordingly, even with the risk of over-treatment for some benign lesions. PMID- 21033261 TI - Subclassification of extranodal involvement in gastric cancer patients. AB - BACKGROUND/AIMS: Extranodal involvement (Ex) has been shown as a negative prognostic factor in several cancers. We classified Ex using 3 methods for gastric cancer and evaluated its influence on patient outcome. METHODOLOGY: The status of Ex in the 103 node-positive patients with curative resection was classified according to: 1) the number of lymph nodes with Ex, 2) the lymph node grouping system, as specified by the Japanese Classification of Gastric Carcinoma, into Ex confined to compartment 1 lymph nodes and Ex detected in compartment 2 and 3 lymph nodes, and 3) the histological type of tumor cells detected in extranodal metastatic sites. RESULTS: Ex was observed in 65 of the 103 patients. An increase in the number of lymph nodes with Ex was associated with a significantly poorer outcome. Patients with Ex detected in compartment 2 and 3 lymph nodes had a significantly poorer outcome. The survival rate of patients with two or more histological types was significantly poorer. Multivariate analysis showed that the method 1) and 2) were independent prognostic factors. CONCLUSIONS: The degree of Ex was shown to be important for determining the prognosis of node-positive gastric cancer patients with curative resection. PMID- 21033262 TI - Usefulness of standardization in spreading of laparoscopy-assisted distal gastrectomy. AB - BACKGROUND/AIMS: This study investigated outcomes of standardized laparoscopy assisted distal gastrectomy (sLADG). METHODOLOGY: Although laparoscopic surgery was performed in patients with early gastric cancers in our hospital, a number of staff surgeons performed individualized variations of the procedure. We introduced sLADG to our hospital, and the short-term outcomes of these patients were examined. RESULTS: The mean surgical duration was significantly reduced (299 min. vs. 358 min, p < 0.01), and the amount of blood loss was also significantly decreased (98 ml vs. 207 ml, p < 0.05) in the standardized procedures in comparison with the previous procedures. However, there was no significant difference in the total number of retrieved lymph nodes among open procedure, conventional and standardized LADG series. Postoperative hospital stay and the occurrence of complications were significantly shorter and less frequent in the sLADG group. CONCLUSIONS: Performance of sLADG by experienced surgeons is expected to promote a safe procedure without reducing surgical curability. PMID- 21033263 TI - Predictive factors of peritoneal metastasis in gastric cancer. AB - BACKGROUND: Preoperative radiological diagnosis of gastric cancer with peritoneal metastasis is still incomplete. Staging laparoscopy is performed for patients who are diagnosed T3 or T4 preoperatively. The aim of this study is to establish a method for predicting peritoneal metastasis. METHODOLOGY: 236 gastric cancer patients who were determined histologically at the final staging were studied. We evaluated whether the parameters of preoperative evaluation such as maximum tumor size, circumferential involvement, macroscopic type, number of metastatic lymph nodes and histological differentiation could predict a peritoneal metastasis. RESULTS: The patients with maximum tumor size > 50 mm in diameter, all 4 cross sectional parts in circumference involved, Type IV tumor, number of metastatic lymph nodes > 3 and histologically undifferentiated type had a significantly higher incidence of peritoneal metastasis, compared with those with other types. Maximum tumor size > 50 mm, all 4 cross-sectional parts involved and type IV were confirmed as independent risk factors by multivariate analysis. A predictive equation "y = 0.018+0.171 (Maximum tumor size > 50 mm)+0.387 (all 4 cross sectional parts involved)+0.183 (type IV)" was established. When y value was set to 0.5, sensitivity and specificity were 78.3%, 88.5%, respectively. CONCLUSION: The predictive equation of peritoneal metastasis revealed satisfactory results and can be regarded as useful in diagnosing peritoneal metastasis. PMID- 21033264 TI - Clinical assessments in patients ten years after pylorus-preserving gastrectomy with or without preserving both pyloric and hepatic branches of the vagal nerve for early gastric cancer. AB - BACKGROUND/AIMS: To clarify the differences in the postoperative quality of life (QOL) of patients after pylorus preserving gastrectomy (PPG) between those with preserved pyloric and hepatic branches of the vagal nerve (PHV) and those without PHV, we investigated the postoperative gastrointestinal symptoms at 10 years after PPG patients with or without PHV. METHODS: Twenty eight subjects who underwent PPG with D2 lymphadenectomy without preserving the PHV (group A: 18 male and 10 female subjects aged 38 to 70 years with a mean age of 60.2 years) were interviewed to inquire about gastrointestinal symptoms (appetite, weight loss, epigastric fullness, reflux esophagitis, and early dumping syndrome), and compared with 30 PPG patients with D1 lymphadenectomy with preserving PHV (group B: 20 male and 10 female subjects aged 33 to 72 years with a mean age of 61.3 years). Esophagogastric endoscopy and abdominal ultrasonography were also studied. RESULTS: There were no differences in the postoperative gastrointestinal symptoms, endoscopic reflux esophagitis, and endoscopic gastritis between groups A and B. However, cholecystolithiasis was significantly found in group A but was not found in group B. In addition, there was significant difference between groups A and B (p = 0.0074). CONCLUSIONS: It is important to preserve the PHV to prevent cholecystolithiasis formation in patients after PPG. PMID- 21033266 TI - Survival predictors of patients with gastric cancer with peritoneal metastasis. AB - BACKGROUND/AIMS: Although many authors investigate the prognostic factors of gastric cancer, there are few comprehensive studies on the surgical results and prognostic factors in patients with gastric cancer with peritoneal metastasis. The aim was to describe the clinicopathological features and prognosis of patients with gastric cancer with peritoneal metastasis. METHODOLOGY: We reviewed the records of 172 consecutive patients diagnosed as having primary gastric cancer with peritoneal metastasis from January 1997 to June 2004. Clinicopathologic prognostic variables were evaluated as predictors of long-term survival by univariate and multivariate analysis. RESULTS: The tumors were characterized by positive lymph node metastasis (93.0%). The 1-year survival rate of patients was 19.3%, and median survival period was 16 months. The 1-year survival rate was influenced by lymph node metastasis, surgery methods, and chemotherapy. Of these, independent prognostic factors were lymph node metastasis (present vs. absent, relative risk 1.671, p = 0.005) and resection (no vs. yes, relative risk 1.402, p = 0.013). CONCLUSIONS: Lymph node metastasis and resection emerged as two independent prognostic factors for long-term survival in patients with gastric cancer with peritoneal metastasis. Palliative resection of the primary tumor is important for appraising the prognosis of patients with gastric cancer with peritoneal metastasis. PMID- 21033265 TI - Prognostic factors in primary gastric non-Hodgkin's lymphoma--a single-center retrospective analysis of 103 cases from China. AB - BACKGROUND/AIMS: There is no gold standard to treat primary gastric non-Hodgkin's lymphoma (PG-NHL). Hence, the establishment of effective prognostic factors of PG NHL is essential for its staging and management. METHODOLOGY: We retrospectively analyzed the clinicopathological features of PG-NHL patients who had been diagnosed from 1990 through 2008 in a Chinese cancer center. Event-free survival (EFS) and overall survival (OS) were primary endpoints. RESULTS: Estimated EFS and OS rate at 5 years were 76.0% and 78.7%, respectively. Log-rank analyses revealed OS was significantly prolonged by the following factors: age < or = 60 years; histology of mucosa-associated lymphoid tissue lymphoma; performance status of 0-1; modified Ann Arbor stage IE or IIE1 disease; normal lactic dehydrogenase level; normal hemoglobin level; normal albumin level; International Prognostic Index of 0 or 1; tumor size < or = 5 cm; and less depth of invasion. Only performance status, modified Ann Arbor stage and albumin level retained their significance for EFS and OS in the multivariate analysis. CONCLUSIONS: We strongly recommend including albumin level in the management of Chinese patients. Further randomized studies with a large number of cases are needed to establish the optimal management for this disease. PMID- 21033267 TI - Hospital has unique marriage of research center and QI team. AB - Two-way communications enhance the work of both teams. Translating research findings to the bedside: a key quality goal. Research center discoveries already have spurred initiatives. PMID- 21033268 TI - Facility dramatically reduces pressure ulcers. AB - Every patient is checked for pressure ulcer development. Formal and informal education seen as critical. Despite success, wound committee continues to monitor progress. PMID- 21033269 TI - Disclose mistakes that affect multiple patients. AB - Staff must have a sense of duty to patients. Policies and procedures should be developed to address issue. Prion diseases present the greatest ethical challenge. PMID- 21033270 TI - ED quality performance moves into public arena. AB - Be sure to share the good news with your administration, so they can use it to help market the hospital. When adverse rankings appear, you have two options: Seek additional resources to improve performance, or challenge the data. Use an automated system to access "real-time" data on your department's performance, so you will always be ready to defend your ED. PMID- 21033271 TI - Many EDs noncompliant with asthma guidelines. AB - Triage based on exacerbation severity. Tailor treatments to specific age groups. Assist patients with arranging post-ED care. PMID- 21033272 TI - TJC suspends 'auto' adverse decision. PMID- 21033273 TI - Most experts predict higher ED volumes. PMID- 21033274 TI - Hearing the music, honing the mind. PMID- 21033276 TI - Window shopping for electric cars. PMID- 21033275 TI - Fudge factor. Did Marc Hauser know what he was doing? PMID- 21033277 TI - Bugs in space. Microscopic miners could help humans thrive on other planets. PMID- 21033278 TI - Nice germs finish last. Resistant bacteria help their kin survive antibiotics, but at a cost. PMID- 21033279 TI - Status update: "I'm so glamorous". A study of facebook users shows how narcissism and low self-esteem can be interrelated. PMID- 21033281 TI - The trouble with e-readers. Electronic books are still far too crude to replace ink and paper. PMID- 21033280 TI - Why women live longer. Stress alone does not explain the longevity gap. PMID- 21033282 TI - Dark worlds. A shadow cosmos, woven silently into our own, may have its own rich inner life. PMID- 21033283 TI - Controlling the brain with light. PMID- 21033284 TI - How to build the supergrid. PMID- 21033285 TI - Phosphorus lake. Strip-mining Florida to fertilize the nation. PMID- 21033286 TI - Dr. unification. Interview by Amir D. Aczel. PMID- 21033287 TI - Halting the world's most lethal parasite. PMID- 21033289 TI - Climate heretic. Why can't we have a civil conversation about climate? PMID- 21033288 TI - From silk cocoon medical miracle. Scientists are crafting arteries, ligaments, circuitry and holograms from worm yarn. PMID- 21033290 TI - How to cope with an uncertain fate. It's time to abandon the fantasy that all nations must first agree on a master climate plan. PMID- 21033291 TI - The skeptic's skeptic. In the battle for ideas, scientists could learn from Christopher Hitchens. PMID- 21033292 TI - The great chemical unknown. Only a tiny fraction of the compounds around us have been tested for safety. PMID- 21033293 TI - Type 1 diabetes and LADA--occurrence of HLA-DRB1 *03 and DRB1 *04 alleles in two age different groups of diabetics. AB - Type 1 Diabetes Mellitus (T1D) with an onset in adulthood and Late Autoimmune Diabetes of Adults (LADA) are connected with autoimmune insulitis (associated with islet cell autoantibodies) and the specific high-risk HLA class II genotype. The study was aimed at analyzing time and clinical characteristics of the diabetics with an onset of the disease after 35 y. (T1D and LADA). Main target of the study was to assess possible role of the old age onset and compare it with diabetics with the onset in the middle age (incl. analyzing HLA-DRB1 genotype). In the study, we included 103 diabetics with an onset of autoimmune diabetes at 35+ y. who were hospitalized and afterwards long-term observed in the diabetological outpatient department. 46 men and 57 women of the average age 65.7 +/- 13.8 y. (range 35-93 y.) were out of this number. 41 were assessed as the T1D patients and 61 as the LADA ones. As a control group we used 99 healthy individuals. Patients of the T1D subgroup developed diabetes in the age of 50.8 +/- 15.1 y. and of the LADA subgroup in the age of 52.6 +/- 12.8 y. Its duration in the time of this study was 10.7 +/- 11.6 y.; respectively 5.3 +/- 7.1 y. Fasting and postprandial C-peptide levels were statistically higher (p < 0.01) in the LADA subgroup vs. T1D. Obesity 1st and 2nd grade were present together only in 12.6%. BMI was not statistically significantly different between both groups. We found in our diabetic patients the predisposition alleles HLA-DRB1*03, HLA DRB1*04 and particularly their combination. The occurrence of these HLA alleles is significantly higher in T1D patients in comparison to control groups (p = 0.01, OR = 4.0). In our study, the occurrence of the susceptible HLA-DRB1*03 and HLA-DRB1*04 alleles in T1D patients is higher than in LADA. The presence of these alleles identifies patients of high risk and requirement of insulin therapy. Since risk alleles are similarly present in middle and old age, environmental factors probably play similar role in these onsets of autoimmune diabetes. PMID- 21033296 TI - Respectful actions: exponential excellence. PMID- 21033294 TI - How will you shine bright? PMID- 21033297 TI - Angela Wright's journey towards making a difference. Interview by Lauren Swain. PMID- 21033298 TI - Enhancing your academic nursing experience. PMID- 21033299 TI - Driving instructors. PMID- 21033301 TI - Narrowing health inequalities in Sri Lanka: issues and challenges. PMID- 21033300 TI - Undergraduate research in nursing. PMID- 21033302 TI - Detection of micrometastases in lymph nodes using reverse transcription polymerase chain reaction (RT-PCR) for cytokeratin 20 (CK-20)--a pilot study. AB - OBJECTIVES: The aim of the study was to detect micrometastases in lymph nodes in patients with rectal cancer following neoadjuvant therapy, staged node negative by routine histology. PATIENTS AND SETTING: Mesenteric lymph nodes from patients who have undergone neoadjuvant therapy for rectal cancer were harvested during surgery. Nodes were bisected and one half was sent for haematoxylin and eosin (H&E) staining and evaluated by a single pathologist. The other half was examined for CK20 by RT-PCR. The technique was validated by testing mesenteric lymph nodes with known metastases and nodes from patients without cancer. Twenty one lymph nodes from 6 patients (median age 46 years, range 25-55) which were negative for tumour deposits by H & E stain were assessed for micro-metastases. RESULTS: All 21 nodes which were histologically negative for metastases were positive for micrometastases. Two nodes with known metastases were positive for CK20 and 3 nodes from non cancer patients were negative for CK20. CONCLUSIONS: Detection of CK20 is accurate in identification of rectal cancer micro-metastasing to lymph nodes. Assessment of nodes by H & E histology risks under staging. PMID- 21033303 TI - Early pregnancy growth and pregnancy outcome in twin pregnancies. AB - OBJECTIVES: The objective of this study was to determine the association of crown rump length (CRL) discrepancy in monochorionic and dichorionic twins with subsequent pregnancy outcomes. METHOD: A retrospective analytical study was performed among 660 twin pregnancies over 12 years in one fetal medicine tertiary referral center in the United Kingdom. A literature search was performed to identify all reports in the English language literature in this topic between 1998 and 2009. RESULTS: Five hundred and six dichorionic and 154 monochorionic twin pregnancies were studied. Median percentage CRL discordance in monochorionic and dichorionic pregnancies was not different (3.9 +/- 8.34, range 0-59 and 3.2 +/- 5.65 range 0-37.5, respectively, p = 0.225). Single or double fetal loss was higher in monochorionic twins than the dichorionic twins. Loss rate was 17.53% (27) and 3.95% (20) respectively (p = < .0001). CRL disparity and birth weight discordancy showed statistically significant correlation (Spearman's rho, p = 0.040). Statistically significant correlation was seen between percentage CRL disparity and pregnancy loss rate (p = 0.008). However, the sensitivity of this CRL discrepancy to detect subsequent fetal loss or birth weight discordance is poor. INTERPRETATION: CRL discrepancy is independent of chorionicity in twins. CRL discrepancy is correlated to subsequent pregnancy loss and birth weight discordance, but the clinical utility of this observation is limited. The difference in twin CRL at 11-14 weeks is likely to represent physiological variation in a majority of cases. PMID- 21033304 TI - Efficacy of 'Thriposha' supplementation in improving the micronutrient status of preschool children. AB - INTRODUCTION: The islandwide comprehensive supplementary feeding scheme, the 'Thriposha' programme has been in existence in the country for over three decades. However, its effectiveness in improving micronutrient status has not yet been evaluated. OBJECTIVE: We examined the effects of 'Thriposha' on micronutrient status, assessed haematologically and biochemically, in young children. METHODS: Preschool children (aged 3-5 years) from two well-baby clinics were grouped into interventional (n = 137) arm and control (n = 130) arm. Children in the interventional group were fed 'Thriposha' (50 g/day) while the control group of children was fed with 50 g 'Thriposha' made without mineral and vitamin premix, for a period of nine months. Serum calcium, ferritin, folate, freeT4, ceruloplasmin, zinc, vitamin A, vitamin D and haemoglobin (Hb) levels were measured before and one week after completing intervention. RESULTS: The baseline Hb levels of the intervention and control groups were 113.20 (SD10.9) g/l and 112.30 (SD 9.0) g/l respectively. After the intervention, the interventional group showed a significant improvement (repeated measures ANOVA, p = 0.02) in the Hb (mean of 118.10 (7.7) vs. 114.70 (7.0) g/l of the control). The prevalence of anaemia dropped from 37% to 15% in the intervention group (p = 0.03). Serum ferritin and ceruloplasmin levels also improved. CONCLUSION: Regular consumption of conventional 'Thriposha' for 9 months led to improvements in Hb, ferritin and ceruloplasmin levels in the blood. PMID- 21033305 TI - A case of embryonal sarcoma of the liver. PMID- 21033306 TI - Chronic intrathoracic gastric volvulus. PMID- 21033307 TI - Thyroid volume in a cohort of Sri Lankan patients: a preliminary report. PMID- 21033308 TI - Quality of life following restorative proctocolectomy for ulcerative colitis and familial adenomatous polyposis. PMID- 21033309 TI - Resection of colorectal liver metastases: single unit experience in Sri Lanka. PMID- 21033310 TI - Isolation of inducible amp C beta-lactamase producing Enterobacter aerogenes from a diabetic foot ulcer. PMID- 21033311 TI - A case of paroxysmal cold haemoglobinuria following chickenpox. PMID- 21033312 TI - An uncommon complication of Salmonella paratyphi A infection. PMID- 21033313 TI - The concept of epileptic networks. Part 1. AB - In this paper we investigate evidences supporting the network concept of epilepsies from different approaches. Firstly the functions of cortical networks in which most of the epileptic networks are embedded, are treated. Then the tentative characteristics of an epileptic network are enumerated and the conversion mechanisms from physiological to epileptic networks are analyzed. Later the role of neuronal oscillations in epileptic networks and aspects of epilepsies provoked by sensory and cognitive tasks is studied. Lastly new fMRI data in mapping BOLD networks underlying spike and seizure discharges are used as arguments in favour of the epileptic network hypothesis. In a second part the well-known epilepsies related, or probably related to physiological networks are shown. Finally consequences of the network approach for creating a new unified epilepsy classification are discussed. PMID- 21033314 TI - Genetic risk factors in Alzheimer's disease. PMID- 21033315 TI - A preliminary study of the frequency of focal neurological deficits in HIV/AIDS patients seropositive for Toxoplasma gondii IgG in Lagos, Nigeria. AB - BACKGROUND: Cerebral toxoplasmosis is a common cause of focal neurologic deficits in HIV/AIDS. Financial constraints and access to neuroradiological facilities limit definitive diagnosis and first-line treatments are largely expensive and cumbersome. OBJECTIVE: This study examined the frequency of focal neurological signs in HIV/AIDS patients with positive Toxoplasma gondii IgG antibodies (and thus at high risk of reactivation), and the relationship to CD4 count. METHODS: Using a case-control design, T. gondii IgG serology was determined in 83 HIV/AIDS patients on HAART and 42 HIV seronegative controls. Neurological evaluation and CD4 count (mm3) was conducted in all subjects. RESULTS: A total of 71 (85.5%) HIV/AIDS patients were seropositive for T. gondii IgG. The IgG seroprevalence was 84.8% for cases with CD4 count < 200 and 86.0% with CD4 < or = 200 (P = 0.46). Of the cases with positive Toxoplasma antibodies, the frequency of neurological lateralizing signs was higher in those with CD4 count < 200 (32.6%) compared to persons with CD4 count > or = 200 (7.1%) (chi2 = 4.90, Fisher exact P <0.01). The mean CD4 count of cases with lateralizing signs was 113.7 +/- 113.9 in contrast to 254.0 +/- 218.9 in those without lateralizing signs (P < 0.01). CONCLUSION: In our study, a higher frequency of focal neurological signs was found in the T. gondii seropositive HIV/AIDS patients with a higher degree of immune compromise (CD4 count < 200). We suggest the adoption of routine prophylactic anti toxoplasma therapy in this subgroup given that cerebral toxoplasmosis is a leading cause of intracranial space occupying lesions in HIV/AIDS. PMID- 21033316 TI - Serum C-reactive protein in Nigerians with type II diabetes mellitus. AB - BACKGROUND: C-reactive protein is an acute-phase proteins, produce in the liver, its release is stimulated by cytokines (interleukin 6 and tumour necrosis factor alpha). Elevated level of it is a risk factor for coronary heart disease. Baseline levels of C-reactive protein in apparently healthy men and women predict long-term risk of a first myocardial infarction. Diabetics are at increased risk for coronary heart disease, data from the Framingham Study showed a two-to three fold elevation in the risk of clinically evident atherosclerotic disease in patients with type II diabetes compared to those without diabetes. However, but data regarding CRP in Nigerian diabetic is lacking. OBJECTIVES: The study was to determine serum C-reactive protein in Nigerian with Type II diabetes mellitus. METHODS: The study design was cross-sectional conducted among patients attending out patient clinic of the Obafemi Awolowo University Teaching Hospitals complex (OAUTHC) Ile Ife, Osun State south western Nigeria. Measurement of C-reactive protein was based on the principle of solid phase enzyme-linked immunosorbent assay (ELISA). RESULTS: A total of 125 consecutive subjects were recruited comprising 75 patients with type II diabetes mellitus with or without hypertension and 50 apparently healthy age-and-sex comparable controls. There was a significant difference between the mean systolic and diastolic blood pressures of the patients and controls. The fasting blood glucose and C-reactive protein were significantly higher in diabetics compared to controls. There was a positive and significant correlation between FBG and CRP in both patients and controls. CONCLUSION: This study showed that diabetics have significantly higher serum C reactive protein compared to the apparently controls. Also there was a positive and significant correlation between C-reactive protein and fasting blood glucose among both patients and controls. PMID- 21033317 TI - Gender variation of bilateral Q-angle in young adult Nigerians. AB - BACKGROUND: The quadriceps femoris angle (Q-angle) is an important indicator of biomechanical function in the lower extremities. It is a quantitative measurement of patella position in respect to the lower extremity alignment. OBJECTIVE: This study was designed to determine gender variation of bilateral Q-angle values in young adults and also to check for symmetry in individual participants. METHODS: A total of 800 participants (400 males and 400 females), who were recruited consecutively participated in the study. They had no history of knee pain or musculoskeletal disorders and no obvious limb length discrepancy. Their ages ranged from 18 to 30 years. They were selected using a non-probability sample of convenience. The Q-angle was measured bilaterally using the universal goniometer with the participants in the erect weight bearing position. The data were analyzed using the independent t - test at 95% confidence interval. RESULTS: The Q-angle valves in the male participants were 14.7 degrees +/- 2.1 for left and 13.0 degrees +/- 1.7 for right lower limbs respectively, while in the female participants, Q-angle values were 16.8 degrees +/- 1.3 and 15.3 degrees +/- 1.0 for left and right lower limbs respectively. Female participants had significantly higher Q-angle values than their male counterparts. The left lower limb recorded a significantly higher Q-angle value in both males and females than right lower limb (p < 0.05). CONCLUSION: Q-angle is bilaterally asymmetric in an individual and higher in female, hence Q-angle measurement should always be bilateral, irrespective of whether one or both knees are involved. PMID- 21033318 TI - Hepatitis C virus co infection in HIV positive patients. AB - BACKGROUND: Hepatitis C virus (HCV) co infection is reported common in HIV positive individuals and also responsible for increasing morbidity and mortality among them. OBJECTIVE: This study was undertaken to determine the prevalence of antibodies to HCV (anti- HCV) among HIV positive patients. METHODS: This cross sectional study was carried out among HIV positive patients and HIV negative blood donors. HIV infection was diagnosed in patients using Determine HIV- 1/2 rapid kits and Elisa based immunocombfirm, while Dialab Elisa kits were used for screening blood donors for HIV and also assaying anti HCV in all subjects. RESULTS: Anti-HCV was detected in 14.7% of patients and 1.1% of HIV negative blood donors. HIV/HCV co-infection rate was highest in the 30-39 years age group (P > 0.05). CONCLUSION: Findings demonstrate a high prevalence with 13 fold higher risk of HCV co infection among HIV-positive patients. PMID- 21033319 TI - Clinicopathological study of male breast cancer in Nigerians and a review of the literature. AB - BACKGROUND: Breast cancer is rare in men, accounting for approximately 1% of all cases of breast carcinoma. OBJECTIVE: To evaluate the incidence, presentation, histopathological types, management and outcome of male patients with breast cancer treated at the University of Benin Teaching Hospital, Benin City, Nigeria. METHODS: A 20 year (1987-2006) retrospective study of all male patients with breast cancer was done. Clinic demographic data regarding age, sex, clinical information, treatment and follow up were obtained from request cards and case files. Slides were retrieved from the archives of the Department of Pathology and reviewed. RESULTS: Sixteen cases of male breast cancer were encountered. This comprised 18.4% of the breast lesions in males and 2.8% of all breast cancers seen in the Department during the 20 year study period. The ages of patients ranged from 35-90 years with a mean age of 64.4 years. Delay in patient presentation to physician ranged from 14-49 months. Clinically, patients presented mostly with a self-detected lump (87.5%), or ulceration (68.8%), nipple discharge (43.8%) and nipple bleeding (25.0%). Unilaterality was observed in 87.5% of cases were while 12.5% of cases were bilateral (metachronous). Invasive ductal carcinoma (81.25%) was the predominant histological type of cancer. Stage IV disease was most commonly encountered (43.8%). Eleven (68.8%) patients had modified radical mastectomy. Only 31.3% patients came for follow-up, for a median duration of 10 months. CONCLUSION: Male breast cancer is rare and patients present late with advanced disease. Education needs to be intensified to increase awareness of the disease. PMID- 21033320 TI - Causes of blindness and low vision in Bayelsa State, Nigeria: a clinic based study. AB - BACKGROUND: No data are yet available on the causes of blindness and low vision in Bayelsa State of Nigeria. OBJECTIVE: The study is to provide baseline data on the causes of blindness and low vision in Yenagoa, Bayelsa State, Nigeria. METHODS: A prospective study was conducted among new consecutive patients presenting at the eye clinic of Niger Delta University Teaching Hospital. Patients with visual acuity of less than 6/18 in the better eye after optical correction or with pin hole as necessary were studied. Their visual acuity was determined using a snellen chart followed by anterior and posterior segment examination using a Haagstreit slit lamp biomicroscope and direct or indirect ophthalmoscope respectively (Keeler). Other information obtained from patients included their age, sex and occupation. MAIN OUTCOME MEASURE: Visual acuity < 3/60 in the better eye and visual acuity < 6/18 in the better eye. STATISTICAL ANALYSIS: STATISTICAL ANALYSIS was done using a scientific calculator. RESULTS: Over a period of one year, 230 patients presented with visual impairement consisting of 124 blind cases and 106 cases of low vision. Their ages ranged from 3 to 90 years with a mean of 48 years. There were 118 males and 112 females giving a male:female ratio of 1:1.1. Cataract and glaucoma were the leading causes of blindness and low vision. Cataract was responsible for 63% of blindness and 49.8% of low vision while glaucoma accounted for 22% of blindness and 17.9% of low vision. The other causes of blindness in decreasing order includes maculopathy (4.3%), retinitis pigmentosa (3.4%), optic atrophy, phtisis bulbi, keratopathy (each 2.6%) and age related macular degeneration (0.9%). The other causes of low vision in decreasing order includes refractive error (15%), maculopathy (5.6), optic atrophy (3.8%), retinitis pigmentosa, retinopathy (each 2.8%) and age related macular degeneration (1.9%). Majority of blindness is avoidable (93.5%), and found in the fifth and sixth decades of life. CONCLUSION: Cataract and glaucoma are the predominant causes of blindness and low vision in the study population and majority of the blindness (93.5%) is avoidable. A more aggressive approach to clear cataract back log and improvement of early diagnosis and treatment of glaucoma are needed to combart blindness in this community. PMID- 21033321 TI - Efficacy of HIV PCR techniques to diagnose HIV in infants born to HIV infected mothers at LASUTH. AB - BACKGROUND: There has been so many difficulties encountered in the diagnosis of HIV infection in infants < 18 months of age born to HIV-infected mother. In these infants, definitive diagnosis can only be carried out by antigen based techniques which are expensive and not widely available in developing countries. OBJECTIVE: To generate information on the rate of mother to child transmission in Nigeria and to compare the efficacies of both the HIV-1 RNA and HIV-1 DNA PCR techniques in the diagnosis of this infections in infants. METHOD: Ninety (90) whole blood samples were obtained from 45 HIV positive mothers and 45 infants born to these mothers from the Department of Obstetrics and Gynaecology, Lagos State University Teaching Hospital (LASUTH), Ikeja, Lagos. The presence of HIV was determined using the Amplicor HIV-1 DNA test and an in-house RNA PCR method. RESULTS: All the infants were HIV antibody positive, however, only 5 infants were positive by HIV-1 DNA PCR, indicating an 11% rate of transmission from HIV positive mothers. Among the 5 infants positive by the DNA PCR, only 4 were positive for the in house RNA PCR. CONCLUSION: The 11% transmission rate recorded in this study was similar to that from mothers' who had Nevirapine ART interventions and both the HIV-1 DNA test and the in-house RNA PCR tests were sensitive and specific in the diagnosis of infection in infants, depending on the level/ state of HIV infection in infants. PMID- 21033322 TI - Effect of aqueous extract of the bark of Carica papaya on testicular histology in Sprague-Dawley rats. AB - BACKGROUND: Males generally have few options for controlling their fertility and these options are far from being satisfactory. There is a great need for research to develop more contraceptive modalities for males. OBJECTIVE: The overall aim of this research was to determine the histological responses of the testes of Sprague-Dawley rats to aqueous extract of bark of Carica papaya using a single daily dose of 100 mg/kg and also to investigate if these responses are reversible or not. MATERIALS AND METHODS: Sixty mature (6-8 weeks old) male Sprague-Dawley rats, divided into 2 equal groups, were used for this experiment. Group 1 rats were fed with 100 mg/kg/day of the extract for 4 and 8 weeks, while group 2 rats served as the control subjects. Each cauda epididymis of the rats was exteriorized, incised and sperm motility and count conducted on expressed fluid. The testes were harvested and processed for histological examination under light microscope. Phytochemical analysis was done to ascertain the main constituents in the extract, while the LD50 was conducted to guide in the dose of administration of the extract. A subgroup of the animals was allowed a recovery period of 8 weeks before sacrifice. RESULTS: The results showed that 500 mg/kg (LD50) of the extract of bark of Carica papaya produced signs of toxicity with mortality of 50% of the rats. The extract at a dose of 100 mg/kg caused histological changes ranging from seminiferous tubular distortion to outright destruction/ degeneration of the seminiferous tubules. In addition, the testicular interstitia of extract-treated rats showed disorganization and hypocellularity. The extract also caused a significant (p < 0.05) reduction in both sperm count and motility. There was no significant reversal of these antispermatogenic effects following a recovery period of 8 weeks. CONCLUSION: Aqueous extract of the bark of Carica papaya has deleterious effects on both the seminiferous tubules and testicular interstitium and deserves to be further investigated as a potential male contraceptive agent. PMID- 21033323 TI - Incidence of postoperative eye infections in a private eye hospital in Lagos, Nigeria. AB - BACKGROUND: There is a dearth of information on postoperative eye infections in Nigeria and most hospitals do not have an infection control program in place. OBJECTIVE: This study was done to investigate the incidence of post-operative eye infections, their potential sources and the preparedness of the hospital to prevent such infections. METHODS: A microbiological survey of all eye surgical procedures between March 2004 and May 2005 was performed. Relevant samples were taken and cultured pre, intra and post operatively as required. Definitions of infections were based on the Centers for Disease Control (CDC) Criteria. In the eye clinic, and operation theatre, infection control procedures and practices were audited using a pre-designed questionnaire. RESULTS: There were 2 cases of post operative eye infections (with Haemophilus influenzae and Corynebacterium species) during the one year of survey of 339 performed surgeries. S. aureus, Coagulase negative staphylococcus (CNS), and Enterobacter spp were cultured from the aqueous humour, as well as pre and post operative conjunctivae swabs of three other patients. Eighty four (24.8%) other patients were colonized post operatively with CNS (32), S. aureus (28), Klebsiella pneumoniae (8), E. coli (5), Corynebacterium species (3), Pseudomonas aeruginosa (1) Proteus mirabilis (4), Enterobacter species alone (1) and in association with CNS on 2 occasions. Seventy eight percent of patients had contact with staff who consistently haboured Staphylococcus species in their nares. Four patients (0.11%) were exposed to surgeons whose hands were contaminated and one eye (0.003%) to contaminated antiseptic solution. Facilities for hand washing and protective clothing were adequate but staffs were observed to perform an inadequate hands scrubbing. Most items were heat sterilized. Cleaning facilities were adequate and the environment was clean. The choice of antiseptic was correct, but that of disinfectant was considered incorrect. The ophthalmic equipments except the eye occluder were appropriately disinfected. Staffs were not protected when handling linen. Infected linens were separated from soiled linens only in the theatre. They were not bagged, and were hand sluiced. The only type of waste that was properly handled was sharps. All waste types were stored together prior to final disposal away from the public. CONCLUSION: The incidence of post-operative infection was 1.69% and their sources were the patients' normal flora. Other potential sources of post-operative eye infections identified included nares of hospital staff, hands of surgeon and hospital disinfectants. Areas of deficiencies in infection control practices, which require proper infection control policies, include hand scrubbing practices, disinfection, linen management and waste handling. PMID- 21033325 TI - Pain management nursing: scope and standards of practice. PMID- 21033324 TI - Seroprevalence of hepatitis C infection in HIV patients using a rapid one-step test strip kit. AB - BACKGROUND: Hepatitis C virus (HCV) and HIV are transmitted via similar routes making co-infection with these viruses a common event. In addition, HIV infection and related immunosupression in patients with hepatitis C may be associated with more rapid progression of liver disease to cirrhosis, end-stage liver disease and death. OBJECTIVE: The study is to determine the seroprevalence of HIV/HCV co infection rate. METHODS: A cross -sectional study was carried out from January to March 2010 at the HIV clinic of the Lagos State University Teaching Hospital. About 5 mls of blood sample was collected from each consenting participant. Sera were subjected to HCV rapid kit as recommended by the manufacturer (Dia Spot HCV one step test strip). The descriptive data was given as means +/- standard deviation (SD). The chi-squared test was used for analytical assessment. The differences were considered statistically significant when P value obtained was < 0.05. RESULTS: The overall seroprevalence rate of HIV/HCV coinfection was 3.3%. Only 6 of 194 female HIV subjects screened tested positive for HCV (3.1%), while 3 of 73 male subjects tested positive for HCV (4.1%) (P value 0.001). None of the 9 co-infected HIV/HCV participants (both male and female) had CD4 count of 350 and above, 3 had a count of 1-100 cells/il., 4 had 100-200, while 2 had 201-350. CONCLUSION: There is the need to include hepatitis C screening routinely in all HIV-infected patients undergoing pre-HAART evaluation in HIV clinics in order to lower liver-related morbidity and mortality associated with them. PMID- 21033326 TI - A rehabilitation hospital approach to safe patient movement. PMID- 21033328 TI - Importance of the Spanish Expert Guidelines for the prevention and treatment of postoperative nausea and vomiting. PMID- 21033329 TI - [The PACE study]. PMID- 21033330 TI - [Transthoracic real-time three-dimensional echocardiography: clinical role, value and limitations in assessing heart valves]. AB - The introduction of three-dimensional echocardiography and its evolution from time-consuming and cumbersome off-line reconstruction to real-time volumetric technique (real-time three-dimensional echocardiography) are one of the most significant advances in ultrasound imaging of the heart of the past decade. This imaging modality currently provides realistic views of cardiac valves capable of demonstrating the anatomy of various heart valve diseases in a unique, noninvasive manner. In addition, real-time three-dimensional echocardiography offers completely new views of the valves and surrounding structures, and allows accurate quantification of severity of valve disease. This article reviews the advantages of real-time three-dimensional echocardiography in assessing heart valves and shows also technological limitations in order to provide the scientific basis for its clinical use. PMID- 21033331 TI - [Tricuspid valve morphology and function evaluated by transthoracic real-time three-dimensional echocardiography]. AB - Tricuspid valve (TV) morphology and function evaluation plays a key role in several cardiac diseases, including left-sided valvular diseases and heart failure. However, TV is structurally complex and, differently from aortic and mitral valves, cannot be visualized in a single two-dimensional echocardiographic view, neither transthoracic nor transesophageal (i.e., simultaneous imaging of the three TV leaflets and their attachment to the annulus is not feasible). Conversely, real-time three-dimensional transthoracic echocardiography allows complete visualization of the TV apparatus from multiple views. This can lead to an improvement of our understanding about the pathophysiological mechanisms underlying TV diseases and functional tricuspid regurgitation, and may suggest new surgical techniques in order to improve surgical outcomes. The present review focuses on the state-of-the-art of real-time three-dimensional transthoracic echocardiography in TV morphology and function evaluation with its clinical applications and limits. PMID- 21033332 TI - [Cardiologic assessment of surviving family members of young victims of sudden cardiac death: diagnostic yield]. AB - Sudden cardiac death (SCD) is one of the most common causes of death in developed countries. In Italy, an annual incidence of 0.7 per 1000 inhabitants per year can be estimated. SCD represents the main cause of sudden death in children, adolescents and young adults and often occurs in young and previously asymptomatic patients. This issue has acquired even greater relevance since implantable cardioverter-defibrillators have proved to be highly effective in preventing sudden death in high-risk subjects. Autopsy findings of young SCD victims include inherited cardiac disorders with a defined morphologic substrate but also hearts without any identifiable structural abnormalities (sudden unexplained death). The potential heritability of the underlying disorder makes surviving relatives at risk of sudden death. A cardiological workup in these families may allow identification of cardiac disease and may unmask affected surviving relatives in whom the disease had remained unrecognized. Cardiological and genetic assessment of relatives of SCD victims based on current literature is reported in this review as well as our experience on SCD in young people in the Lazio Region (Italy) between 2001 and 2008. PMID- 21033333 TI - [Cardiological follow-up in patients with Fabry disease]. AB - Fabry disease is a rare tesaurismosis due to a deficit of the lysosomal enzyme activity of alpha-galactosidase, needed for the normal catabolism of globotriaosylceramides (GL3). Fabry cardiac involvement has several clinical manifestations: concentric left ventricular hypertrophy without left ventricular dilation and severe loss of left ventricular systolic function, mitral and aortic valvulopathy, disorders of the atrioventricular conduction or repolarization, and compromised diastolic function. Differentiating Fabry disease from similar conditions is often quite straightforward, e.g., cardiac amyloidosis is often associated with low electrocardiographic voltages, and systemic symptoms are usually associated with hemochromatosis and sarcoidosis. However, sometimes second-level (genetic analysis, alpha-galactosidase levels) or invasive investigations are required, which can include endomyocardial biopsy. Diagnostic imaging techniques have been described, but they lack specificity. Echocardiographic imaging with tissue Doppler analysis and/or strain rate analysis can allow diagnosis of Fabry disease even before left ventricular hypertrophy becomes apparent. This review illustrates the techniques for staging cardiac involvement and damage in Fabry disease and for the long-term follow-up of Fabry patients with or without cardiac involvement. Careful cardiac monitoring is especially important in elderly female carriers, who often develop renal disorders and/or left ventricular hypertrophy as the only manifestations of their late Fabry disease. In some clinical series, Fabry disease was diagnosed in 12% of women with adult-onset hypertrophic cardiomyopathy. Cardiological problems and outcomes of enzyme replacement therapy, associated with or without other cardiological treatments, are also discussed. PMID- 21033334 TI - [Medical-legal evaluation of hypertrophic cardiomyopathy]. AB - Hypertrophic cardiomyopathy outlines a pathological condition of considerable interest not only in the field of cardiology but also for medical-legal aspects. Along with a great variability in symptoms, the evaluation of injury from a medical-legal point of view is not always of easy interpretation. The purpose of this review is to provide a targeted medical-legal evaluation on the basis of well known clinical and prognostic indications, also with reference to the quality of life. PMID- 21033335 TI - [A new setting of opportunistic cardiovascular screening: from blood donation to preventive cardiology. Preliminary results of the Cardiorisk program]. AB - BACKGROUND: Cardiovascular diseases remain the leading cause of mortality and disability in developed countries. Therefore, it is necessary to increase a policy of primary prevention. The most recent European guidelines recommend the use of the absolute risk profile as a tool to identify high-risk individuals, but also underline the need for interventions on the whole population. They also mentioned the concept of opportunistic screening for cardio- and cerebrovascular risk factors. METHODS: From September 2004 to December 2008, 13 619 consecutive blood donors were evaluated to determine the absolute risk profile by using the CUORE Project score. Inclusion criteria were age between 35 and 69 years, no evidence of cardiovascular disease, 12 h fasting, and informed consent. All blood donors underwent physical examination and blood tests. The absolute risk profile system includes 8 variables: age, gender, diabetes, smoking habit, systolic blood pressure, total and HDL cholesterol, and antihypertensive therapy. The population was classified into five risk categories (<5%; 5-10%; 10-15%; 15-20%; > or =20%). The results were analyzed according to age and gender. RESULTS: The mean risk score was 2.9 +/- 3 in men and 0.8 +/- 1.04 in women. Furthermore, the proportion of subjects at low risk was high even in the most advanced age groups in both sexes, differently from the general population. In particular, in young and female subjects the risk score did not exceed 20%. The proportion of men at high risk increased in adulthood, varying between 0.5% in the 50-59 age range to 4% in subjects > or =60 years. CONCLUSIONS: Our results demonstrate the feasibility of a primary cardiovascular prevention program in a new opportunistic setting, not assessed previously. The implementation of this program is a valuable tool not only to identify high-risk subjects but also to maintain a favorable risk profile in low-risk subjects over time. PMID- 21033336 TI - [Treatment of chronic total coronary occlusions by the subintimal tracking and reentry modified technique. The contrast-guided STAR technique]. AB - BACKGROUND: Previous data showed that recanalization of chronic total occlusions (CTO) with the subintimal tracking and reentry (STAR) technique is feasible. However, this technique is challenging and requires skilled operators to be performed. The aim of this study was to evaluate procedural and clinical outcomes of patients undergoing a contrast-guided STAR procedure. METHODS: All consecutive patients (n=121) with coronary CTO treated with the contrast-guided STAR technique in three Italian centers were included in this study, after failure of conventional CTO approaches. RESULTS: The right coronary artery was involved in 76.8%, with blunt morphology in 62.8%. Angiographic and procedural success rates were 82.6% and 64.4%, respectively, with a 69.4% rate of complete recanalization. Stent implantation was performed in 81.8% of cases, using drug-eluting stents in 94.4%. Procedural complications occurred in 7.4% of cases. During follow-up no episodes of myocardial infarction were observed, but one cardiac death (0.8%). No definite or probable stent thrombosis was reported. The overall rate of target lesion revascularization was 21.4%. CONCLUSIONS: This study demonstrated that the contrast-guided STAR technique appears to be a feasible and relatively safe procedure when performed as rescue technique after failure of conventional CTO approaches. However, this procedure is limited by a high rate of target lesion revascularization and a second procedure may be necessary to obtain a definitive result. PMID- 21033337 TI - [Indications for cardiology consultation and management of cardiac patients who will undergo surgical or endoscopic procedures: the proposal of the University Hospital of Trieste, Italy]. AB - The number of patients affected by cardiovascular disease admitted to internal medicine and geriatric wards is expanding due to the increasing prevalence of cardiovascular disease in the ageing population. This contributes to a growing demand for cardiology consult visits, with requests for perioperative risk stratification for non-cardiac surgery or endoscopy, and general clinical management. This document was jointly drafted by the Cardiology and Anesthesiology departments, medical and surgical departments, and endoscopy services of the Azienda Ospedaliero-Universitaria "Ospedali Riuniti" in Trieste (Italy). It addresses critical issues such as antiplatelet and anticoagulant therapy in non-cardiac surgery, electric device management, and prophylaxis of bacterial endocarditis. It provides general guidelines and appropriateness criteria, prompted by the Joint Commission International and approved by the Hospital Guidelines Committee. It provides a basis for periodic educational meetings, and will be periodically updated. Periodic audits will monitor its application, and critical and controversial points, in order to promote quality of health care, organizational efficiency, and appropriateness. PMID- 21033338 TI - [Rare endocarditis due to Abiotrophia defectiva. Case report and literature review]. AB - Endocarditis by Abiotrophia defectiva is rare but associated with high rates of complications and mortality. The microbiological identification is challenging. Two cases without preexisting valvulopathy and one case with mitral-aortic involvement are described in the literature. A case of this subacute form of endocarditis, with normal mitral and aortic valves, is reported. Surgery was necessary, and mitral repair and aortic homograft implantation were performed with good 3-month results. In case of subacute endocarditis, especially when etiology is difficult to detect, Abiotrophia defectiva should be suspected. PMID- 21033339 TI - [Occasional evidence of pneumopericardium after pericardiocentesis]. PMID- 21033340 TI - [Structure and functional organization of arrhythmology]. PMID- 21033341 TI - [Expression of several domains of twitchin and myorod in the ontogenesis of mussel Mytilus trossulus]. AB - The expression of MLCK- and PEVK-domains of twitchin, as well as the unique N terminal domain of myorod in early development of the mussel Mytilus trossulus has been studied. The MLCK-domain of twitchin and the unique N-terminal domain of myorod appear at the early stages of development, whereas the PEVK-domain of twitchin is present only in muscles of adult mussel. The sizes of genes of the N terminal domain of myorod, obtained at the blastula stage and from the adult animal are similar, but the proteins have significant differences in the amino acid sequences. Consequently, myorod and twitchin appear at early stages of larval mussels before the formation of "adult" muscles capable of catch contraction, and at these stages both proteins are isoforms, which differ from the isoforms of adult animals. It is possible that the MLCK-domain in the "larval" isoform of twitchin is necessary for regulating the formation of the contractile apparatus of molluscan smooth muscles, while the PEVK-domain is important for the regulation of the catch state in muscles of adult animals. PMID- 21033342 TI - [Fluorescence analysis of the action of soluble derivatives of fullerene C60 on amyloid fibrils of the brain peptide Abeta(1-42)]. AB - It has been shown by fluorescence analysis in vitro that the water-soluble sodium salt of the polycarboxylic derivative of fullerene C60, fullerenol, and complexes of fullerene C60 with polyvinylpyrrolidone (mol. wt. 25000 and 10000) destroy amyloid fibrils of the brain peptide Abeta(1-42) and prevent their formation. The results of fluorescence analysis confirmed the data obtained earlier by high resolution electron microscopy. Fluorescence analysis and electron microscopy are complementary methods for the selection of effective antiamylod drugs. PMID- 21033343 TI - [Thin filaments of molluscan catch muscles contain a calponin-like protein]. AB - A novel 40 kDa protein was detected in native thin filaments from catch muscles of the mussel Crenomytilus grayanus. The MALDY-TOF analysis of the protein showed a 40% homology with the calponin-like protein from the muscle of Mytilus galloprovincialis (45 kDa), which has a 36% homology with smooth muscle calponin from chicken gizzard (34 kDa). The amount of the calponin-like protein in thin filaments depends on isolation conditions and varies from the complete absence to the presence in amounts comparable with that of tropomyosin. The most significant factor that determines the contact of the protein in thin filaments is the temperature of solution in which thin filaments are sedimented by ultracentrifugation during isolation. At 22 degrees C and optimal values of both pH and ionic strength of the extraction solution, total calponin-like protein coprecipitates with thin filaments. At 2 degrees C it remains in the supernatant. The 40 kDa calponin-like protein from the mussel Crenomytilus grayanus has similar properties with smooth muscle calponin (34 kDa). It is thermostable and inhibits the actin-activated Mg -ATPase activity of actomyosin. In addition, the 40 kDa calponin-like protein isolated without using thermal treatment contains endogenous kinases. It was found that the calponin-like protein can be phosphorylated by endogenous kinases in the Ca -independent manner. These results indicate that the calponin-like protein from the catch muscle of the mussel Crenomytilus grayanus is a new member of the calponin family. The role of proteins from this family both in muscle and ponmuscle cells is still obscure. We suggest that the calponin-like protein is involved in the Ca -independent regulation of smooth muscle contraction. PMID- 21033344 TI - [Role of light chains of myosin in the regulation of contraction of vertebrate striated muscles]. AB - The data of the study on Ca2+ sensitivity of ATPase activity of myosin from vertebrate striated muscles in the presence of actin and the conditions of its manifestation and disappearance are presented. The role of Ca2+ sensitivity of actin-activated myosin ATPase in the regulation of contraction of vertebrate striated muscles is discussed. PMID- 21033345 TI - [Purification of the mitochondrial calcium uniporter from the beef heart and characterization of its properties]. AB - A low-molecular-weight component (LMC) inducing selective transport of calcium across the bilayer lipid membrane has been isolated from mitochondria of the bovine heart by the method developed in our laboratory, which excludes the use of detergents and proteolytic enzymes. It was shown that, in the presence of 10 mM CaCl2, LMC forms conduction channels in the membrane multiples of 5 pS. The specific inhibitor of mitochondrial calcium uniporter, ruthenium red, closes Ca2(+)-induced channels formed in the membrane by LMC. In the absence of calcium or in the presence of potassium ions only, the component is incapable of forming channels of conduction. It was shown using nuclear magnetic resonance that LMC is a complex consisting of lipids, amino acids, and sugars with a molecular weight of 1-2 kDa. PMID- 21033346 TI - [Localization in a cell of a protein forming the ATP-dependent potassium selective channels in the bilayer lipid membrane. An ultrastructural study]. AB - The localization in the cell of the protein forming the ATP-dependent potassium selective channels in the bilayer lipid membrane has been studied. The electron microscope investigation of rat liver and heart tissue sections after their incubation with Abs against this protein and the visualization of the protein with secondary Abs conjugated with colloid gold were carried out. Colloid gold particles were observed both in mitochondrial membranes and in membranes of endoplasmic and sarcoplasmic reticulum. In heart mitochondria, these particles were significantly greater than in liver mitochondria. The localization of the channel protein both in mitochondria and reticulum, as well as the structural similarity between the mitochondrial channel and the precursor of calreticulin suggest that the channel protein belongs to the family of calreticulins. The possible function of the protein as a channel subunit of the mitochondrial ATP dependent potassium channel is discussed. PMID- 21033347 TI - [Effect of hypoxenum on bioenergetic processes in mitochondria and the activity of ATP-sensitive potassium channel]. AB - The effect of hypoxenum on bioenergetic processes in heart and liver mitochondria of rats, connected with respiration, the generation of hydrogen peroxide, and the activity of ATP-sensitive K-channel ((mitoK)ATP) has been studied. It was shown that hypoxenum in the concentration range of 0.05-10 microg/ml stimulates respiration, increases the coupling in the respiratory chain, and enhances the formation of H2O2 and energy-dependent swelling associated with potassium transport in mitochondria. Hypoxenum removes the inhibitory effect of ATP on the energy-dependent swelling of mitochondria and partially reduces the accumulation of H2O2 in the presence of ATP. The role of antihypoxic and antioxidant action of hypoxenum associated with the activation of (mitoK)ATP is discussed. PMID- 21033349 TI - [Effect of functional unloading and dystrophin deficit on the local hyperpolarization of the postsynaptic membrane of a skeletal muscle fiber]. AB - The data have been obtained that confirm the identity of the electrogenic mechanism of hyperpolarization by nanomolar concentrations of cholinergic ligands in the extrasynaptic region and endogenous nonquantal acetylcholine in the synaptic region of a skeletal muscle fiber. In both cases, this mechanism is realized through the involvement of the alpha2 isoform of Na, K-ATPase and operates in the absence of Na+ entry through membrane channels. At the same time, there are peculiar properties which take place under functional disorders. Thus, the effectiveness of this mechanism in the synaptic region selectively increases under rat hindlimb unloading and decreases in case of dystrophin deficit in mdx mice. The last fact suggests that dystrophin is a molecular component that is essential for the functioning of the electrogenic mechanism of local hyperpolarization of the end-plate membrane. PMID- 21033350 TI - [About possible specialization of different compartments of a motoneuron axon for synthesis of specific proteins]. AB - The spontaneous quantum secretion of neurotransmitter and its regulation through the system of presynaptic acetylcholine receptors have been studied on a neuromuscular preparation of rat m. soleus of intact animals and animals in which the axonal transport was blocked via the application of colchicine to the sciatic nerve. It was shown that, after six days of colchicine application, the spontaneous quantum secretion, the reaction of presynaptic membrane, and the reaction of neurosecretory apparatus to the depolarization of nerve endings via increase of the content of potassium ions in the environment and to the activation of presynaptic receptors by carbachol are not disturbed. Keeping in mind a rather short half-life of proteins that take part in the exocytosis and its regulation, it may be concluded that their functioning does not depend on the state of the axonal transport. These data correspond to the hypothesis put forward earlier that the synthesis of some proteins performing their function in nerve terminals occurs directly at the site of their utilization but not in the perikaryon, as it has been traditionally assumed. PMID- 21033348 TI - [The role of the voltage-dependent anion channels in the outer membrane of mitochondria in the regulation of cellular metabolism]. AB - The role of the voltage-dependent anion channels (VDAC) harbored in the outer membrane of mitochondria in the regulation of cellular metabolism was investigated using an experimental model of ethanol toxicity in cultured hepatocytes. It was demonstrated that ethanol inhibits State 3 and uncoupled mitochondrial respirations, decreases the accessibility of mitochondrial adenylate kinase localized in the intermembrane space of mitochondria, and suppresses ureagenic respiration and synthesis of urea in cultured hepatocytes. Increasing the permeability of the outer mitochondrial membrane with closed VDAC with high concentrations of digitonin (> 80 microM), which creates pores in the membrane, allowing the alternative bypass of closed VDAC, and restores all reactions suppressed with ethanol. It is concluded that the effect of ethanol in hepatocytes leads to global loss of mitochondrial functions due to the closure of VDAC, which limits the free diffusion of metabolites into the intermembrane space of mitochondria. Our studies demonstrated that ethanol affects the main mitochondrial functions and revealed the role of VDAC channels in the outer mitochondrial membrane in the regulation of liver specific intracellular processes such as ureagenesis. The data obtained can be used for the development of pharmaceutical drugs that prevent the closure of VDAC in mitochondria of ethanol oxidizing liver, thus protecting liver tissue from the hepatotoxic action of alcohol. PMID- 21033351 TI - [Cytoskeletal regulation of the cellular function by dopamine]. AB - The interaction of dopamine with model membranes, isolated G-actin, and living cells, such as Mauthner neurons and fibroblast-like BHK-21 cells has been studied. It was found that in vitro dopamine passes through the phospholipid membrane and directly polymerizes G-actin due to incorporation into threads as their integral part. In in vivo conditions, it penetrates inside the cell and induces the appearance of a network of actin filaments in loci rich in globular actin. The data suggest that there exists a mechanism of dopamine interaction with living cells, which is based on direct polymerization of cytosolic G-actin as its cellular target. The reorganization of the actin cytoskeleton leads to changes in the morphofunctional status of cells. PMID- 21033352 TI - [Is the microtubule disruption-induced alteration of peroxide concentration a factor inhibiting the assembly of ribonucleoprotein stress granules?]. AB - It has been examined whether the destruction of cell microtubules affects the increase in the intracellular hydrogen peroxide concentration caused by sodium arsenite, which induces the formation of stress ribonucleoprotein granules. As expected, sodium arsenite caused a 50% increase in hydrogen peroxide concentration in HeLa cells; on the other hand, another stress granule inducer tert-buthylhydroquinone did not affect the peroxide concentration. The disruption of microtubules by nocodazole or vinblastine also resulted in some increase in the intracellular peroxide concentration,y taxol did not affect it. The combined treatment of cells with and the microtubule stabilization by taxol did not affect it. The combined treatment of cells with arsenite and antimicrotubule drugs caused an additive effect, and the peroxide concentration increased twice or more. Thus, the inhibition of stress granule formation after microtubule disruption cannot be explained by a decrease in peroxide concentration as compared with the affect of arsenite. PMID- 21033353 TI - [Familial Alzheimer's disease mutations in the presenilin 1 gene reduce cell-cell adhesion in transfected fibroblasts]. AB - Experimental evidence has been obtained that mutations in the presenilin 1 (PS1) gene in familial Alzheimer's disease can lead to the disturbance of cell adhesion in model cell cultures. It was shown that, in L fibroblasts of mice with stable expression of GFP-PS1 cDNA containing G209V or E319G mutations, cell-cell interactions and the accumulation of GFP-PS1 cDNA in intercellular contacts are disturbed. Similar results were obtained in transfected human epithelial Hep2 cells. It is assumed that mutations in familial Alzheimer's disease lead to the disturbance of the functions of presenelin 1 in cell adhesion. PMID- 21033354 TI - [Effect of low-intensity magnetic fields on the development of satellite muscle cells of a newborn rat in the primary culture]. AB - The influence of Earth magnetic field shielded down to 0.3 microT and static magnetic field (60-160 microT) on the proliferation and differentiation of satellite muscle cells in the primary culture has been investigated. A stimulatory effect of static magnetic fields on the rate of the formation of massive multinucleated myotubes and an increase in the intracellular calcium concentration ([Ca2+]i) have been detected for magnetic fields of the microtesla range. On the other hand, it was shown that the reduction of earth magnetic fields to 0.3 microT leads to the inhibition of proliferation and differentiation of skeletal muscle cells in the primary culture. Since the formation of contractile myotubes during in vitro experiments is similar to the regeneration of skeletal muscle fibers under muscle damage in vivo, it may be concluded that weak magnetic fields have a strong effect on intracellular processes by influencing all phases of muscle fiber formation. It is necessary to take this fact into consideration when forecasting probable complications of skeletal muscle regeneration during long-term exposure of man to low-intensity magnetic fields and also for the potential use of low static magnetic fields as a tool to recover the affected myogenesis. PMID- 21033355 TI - [Electron probe microanalysis of potassium, sodium, and chlorine levels in the cardiomyocyte cytoplasm during acute ischemia]. AB - Electron probe microanalysis was applied to determine cytoplasmic elemental (K, Na, Cl) concentrations in cardiac cells of the rat (Wistar). Potassium, sodium and chlorine contents were measured in papillary muscle myocytes of the rat heart perfused by the Langendorff's procedure. Ischemic depletion was created by perfusion with deeply deoxygenated Tirode's solution in the absence of glucose. It was found that the initial phase of acute ischemia is characterized by the potassium deficiency and the accumulation of sodium and chlorine in cardiac myocytes. It should be noted that changes in the total charge of the main intracellular cations (K+, Na+) do not compensate for the increased chlorine concentration. This result can be accounted for by the appearance of ionic (K+ and Cl-) transport coupled with the removal of lactate anions produced in cardiomyocytes during anaerobic glycolysis. PMID- 21033356 TI - [Rho-associated protein kinase is involved in establishing the contractile phenotype of cardiomyocytes]. AB - It has been shown that Y-27632, an inhibitor of Rho-associated kinase, delays sarcomere assembly in rat neonatal cardiomyocytes pretreated with angiotensin II. Y-27632 affects the beat rate of cardiomyocytes; however, this effect is only observed at high cell density and, therefore, seems to be related to the formation of gap junctions between adjacent cardiomyocytes. Consistent with this suggestion, we established that Rho-associated kinase is localized in myofibrillar Z-discs of human myocardium and intercalated discs, the structures enriched in gap junctions. We propose that Rho-associated kinase participates in the maturation of the myocardial contractile system through phosphorylation of its molecular targets in Z-discs and intercalated discs. PMID- 21033357 TI - [Unbiased criteria for estimation of the transition from unordered to ordered motor activity of the olfactory cilia]. AB - Unbiased criteria (Lissajous figures, entropy, and harmonic spectra) have been developed to estimate the transition from an unordered to an ordered motor activity of olfactory cilia, which occurs by the action of odorants on flagellata. PMID- 21033358 TI - [A mathematical model for sarcomere mechanics in cross-striated muscles taking into account the stretch and twist of actin filaments]. AB - A model of sarcomere mechanics, which takes into account the elongation of the actin and myosin filaments and twisting of the actin filaments during muscle contraction is suggested. The model accounts for the experimentally observed phenomena of the stretch and twist of actin filaments due to strong binding of myosin heads and pulling force. Some model parameters were estimated from published experimental data. The results of modelling suggest that the twist of actin filaments may play an essential role in mechanical responses of contracting muscle fibres to stepwise changes in their length. PMID- 21033359 TI - [Propagation of shear waves in the muscle tissue]. AB - A mathematical model of the propagation of acoustic shear waves in muscle tissue is considered. The muscle is modelled by an incompressible transversely isotropic viscoelastic continuum with quasi-one-dimensional active tension. Two types of shear waves in an infinite medium have been established. The waves of the second type (transverse) propagate without attenuation even when myofibril viscosity is taken into account. A problem of standing transverse waves in a rectangular layer has been investigated numerically. The values of the problem parameters have been found for which the active tension or muscle tonus is easily estimated from the characteristics of standing waves. This value is informative for the diagnosis of muscle state. PMID- 21033360 TI - [Mechanical properties of the passive myocardium: experiment and a mathematical model]. AB - A three-dimensional mathematical model of the rheological properties of a morphofunctional unit of the myocardium has been constructed, which consists of transversal and longitudinal elastic elements and tilted viscoelastic elements hinged without friction. The parameters of the viscosity and elasticity of structural elements of the model do not depend on the deformation value. The model makes it possible to adequately describe the features of the viscoelastic behavior of isolated samples of the passive myocardium and of the myocardium under longitudinal strain. A good agreement between the calculated and experimental data for an intact preparation of the rat myocardium and a preparation with removed cardiomyocytes has been shown. PMID- 21033361 TI - [Effect of isoproterenol on contractility of the heart papillary muscles of a ground squirrel]. AB - The effect of isoproterenol (1 microM) on the force of isometric contractions (0.1-1.0 Hz, 30 +/- 1 degree C, 1.8 mM Ca2+) of papillary muscles of the right ventricle of the heart of the ground squirrel during summer activity (n = 5) and hibernation (activity between hibernation bouts, n = 4; torpor, n = 4; and arousal, n = 5) has been studied. It was shown that isoproterenol increases the force of contraction (positive inotropic effect) in active summer ground squirrels by 20 +/- 3 and 61 +/- 7% at stimulation frequencies of 0.4 and 1.0 Hz, respectively. The isoproterenol-induced increase in the force of contraction in animals during hibernation is brief (within 3 min after the onset of treatment) and this parameter decreases by 30-50% of the control level (negative inotropic effect) at stimulation frequencies from 0.3 and 0.8 Hz. The positive inotropic effect of isoproterenol in active summer ground squirrels is associated with a decrease in the relative value of the potentiating effect of the pause (qualitative indicator of calcium content in the sarcoplasmic reticulum), and the negative inotropic effect, with its increase. It was found that the inotropic effect of isoproterenol in all groups of animals examined (irrespective of its direction) is accompanied by an acceleration of the velocity of the contraction relaxation cycle. The dependence of the effect of isoproterenol in the heart of hibernating animals on seasonal changes in the calcium homeostasis and the activity of the sympathetic nervous system is discussed. PMID- 21033362 TI - [Effects of nifedipine on the mechanical properties of sarcolemma and modulation of calcium accumulation dynamics in fibers of the rat soleus muscle under short term hypogravity conditions]. AB - It has been shown that the modulation of the mechanical properties of sarcolemma by nifedipine may be related to the dynamics of accumulation of calcium ions under short-term rat hindlimb suspension. The basal calcium level was measured by the fluorescence probe Fluo-4AM, the transversal stiffness of different parts of the contractile apparatus and sarcolemma was estimated by atomic force microscopy, and the content of desmin was determined by gel electrophoresis with immunoblotting. It has been found that nifedipine has a protecting effect on muscle fibers under hypogravity by decreasing the degradation of desmin and proteins that determine the transversal stiffness of sarcolemma and the contractile apparatus, and the intensity of the increase in the basal calcium level. It was shown that the selective blocking of L-channels leads to an increase in the basal calcium level in intact soleus fibers. At the same time, the transversal stiffness of sarcolemma and the contractile apparatus increased. The mechanism of this increase is still unclear; however, it is assumed that it mediates the protecting action of nifedipine. PMID- 21033363 TI - [Electrocardiographic image of myocardial ischemia: real measurements and biophysical models]. AB - The peculiarities of the genesis of electrocardiosignal under myocardial ischemia in connection with an increase of its electrical inhomogeneity, as well as the electrophysiological mechanisms of morphological changes of the T wave of the electrocardiogram, including its "symmetrization" have been considered. A systemic approach to the problem has been used, which combines the mathematical, computer, and physiological modeling of the cardiac electrical activity with studies of the electric field of the human heart in terms of biophysical models. A database for the repolarization parameters of experimental electrocardiosignals ("Norm" and "Ischemia" samples) has been formed. The parameters of the ST-T interval and T wave, which could characterize the symmetry of the latter, and some additional properties of the repolarization process have been obtained. The methods of mathematical modeling were used also. Computer experiments were carried out on a system for 3-D modeling of the cardiac electrical activity at different structural levels of the object. By the results of preliminary analysis, the betaT index, which is calculated as the ratio of two maximum absolute values of the derivative of the cardiosignal at the left and right of the T wave apex, has been chosen as one of the main diagnostic markers of ischemia. There is reason to believe that the use of the betaT index allows one to recognize those deviations from the norm that are usually hidden from a physician in traditional ECG analysis. The ratios of repolarization intervals inside of the generalized QT interval have also appeared potentially informative. With the purpose to test and correct the hypotheses for conducting further investigations, some preliminary experiments on a low-resolution model for several alternatives of the degree, localization, and extensiveness of ischemia have been carried out. The results obtained at the first stage of the team-work are essential to the understanding of mechanisms of the genesis of an electrocardiographic image for myocardial ischemia and of interest for the biophysically sound development of new algorithms for computer cardiodiagnostics. PMID- 21033364 TI - [The role of recipient cells in the mechanism of pathological calcification of heart valve and vascular transplants]. AB - It was found using the model of subcutaneous implantation in rats that the calcification of the aorta wall occurs by two mechanisms of which one is dependent on, and the other independent of the migration of recipient cells to the transplant. PMID- 21033367 TI - [Basic principles of creation of multilevel multistage mathematical model of aging]. AB - Current knowledge on the aging allows to elaborate approaches to the creation of multilevel model of multistage of human aging taking into consideration events during the aging at various levels of integration: molecular, cellular, tissue, organ, systemic, organism. The present paper have deals with main states of the mathematical model of multistage aging, principles of its construction, applicability and evaluation of its prognostic power. There are 3 levels of integrative systems: homeostatic (organismal), systemic and cellular-molecular. The definitions of normal and pathological aging are given. The samples of various patterns of aging under the influence of factors accelerating aging (constant illumination or alimentary obesity) or under the factors slowing down aging (treatment with metformin or melatonin) are discussed. PMID- 21033365 TI - [Changes in the diaphragm muscle and its feed artery after chronic respiratory airway obstruction in rats]. AB - A chronic respiratory load was produced in Wistar rats by tracheal binding to produce a twofold increase of pleural pressure oscillation amplitude during respiration. Eight weeks after the surgery, a higher proportion of type-I muscle fibers (MFI) in the costal diaphragm along with a greater MFI cross-section area and a higher succinate dehydrogenase activity in MFII in the crural diaphragm were observed. During recording the mechanical activity of ring preparations of diaphragm arteries under isometric conditions, an increase in endothelium dependent relaxation was found, whereas endothelium-independent relaxation and arterial reactivity to noradrenaline did not change. Tracheal binding did not produce any changes of MF in the gastrocnemius muscle, but endothelium-dependent relaxation of gastrocnemius feed arteries was reduced. We conclude that chronic respiratory load affects the endothelial function in diaphragm arteries in a manner favorable for blood flow control in the diaphragm. Functional alterations in gastrocnemius arteries may be associated with the reduced locomotor activity of operated rats. PMID- 21033366 TI - [Serapeo Temple in Pozzuoli, Italy--the unique gauge for the sea (world ocean) level and the Earth surface temperature for over 2100 years]. AB - The changes in the sea level relative to the position of the Serapeo Temple in Pozzuoly (Italia) over a period of 2100 years are discussed in the context of the well known periods of climate cooling off (Neoglacial, Little Ace Period) and climate warming (Middle Ages Optimum, Modern climate warming). It is noted that the rate of sea level lifting relative to the position of the Serapeo Temple in the modern phase of climate warming, which began the end of the 18th Century is approximately two times higher than in the previous phase of climate warming in the period from the fifth to the mid-tenth century A.D. This indicates that not only the natural cyclic component contributes to the mechanisms of Modern Climate warming but also the anthropogenic component of approximately equivalent power, which results from the waste of CO2 caused by the burning of fossilized fuels. PMID- 21033368 TI - [The mechanism of phenoptosis: 2. Hayflick limit is caused by the programmed attenuation of bioenergetics]. AB - This article continues earlier started theme on a substantiation of the programmed aging mechanism (phenoptosis). The concept underlying this mechanism is that the life represents a lot of the interconnected physical and chemical processes moving by the bioenergetics. The gradual programmed decrease of the level of bioenergetics causes the slow and coordinated attenuation of all physiological functions, i.e. aging. For a convincing substantiation of such mechanism it is necessary to show, how attenuation of bioenergetics causes the basic nocuous processes accompanying aging. It is shown earlier that the age dependent decrease in level of bioenergetics causes increase in production of reactive oxygen species by mitochondria and decrease in overall level of protein synthesis. The proof that Hayflick limit is also caused by the decrease in level of bioenergetics is presented in this article. Decrease in level of bioenergetics below certain critical level deprives a cell the ability to pass the restriction point of G1-phase of proliferative cycle. The inhibitor of cyclin-dependent kinase, p27, prevents the passage through this critical point in all normal cells. During division of normal somatic cells p27 is removed by cyclin E-Cdk2 complex. Interaction p27 with cyclin E-Cdk2 complex can have two consequences. At the normal physiological level of bioenergetics the cyclin E-Cdk2 phosphorylates p27, then the latter is destroyed by proteolytic enzymes--the cell enters in S phase. When the programme decreases the bioenergetics level below certain value the cyclin E-Cdk2 becomes the target for p27. As a result the inhibitor evacuation stops and restriction point becomes closed--a cell enters irreversible proliferative rest. PMID- 21033369 TI - [On thermodynamic theory of evolution and aging of living beings]. AB - The author states, that the thermodynamics is driving power of evolution and development. The evolution is characterized by a change of systems and objects of the universe. Evolution, phylogeny and ontogeny include spontaneous and non spontaneous processes. PMID- 21033370 TI - [Circumstances of the longevity of bats (based on the studies of bats over the territory around Saint-Petersburg)]. AB - According to Medawar's concept on the accumulation of harmful mutations, bat longevity should be explained by the fact, that they have no enemies: since the organisms were not being exterminated at the young age, the selection towards longevity took place at their ancestors; the specific mutations causing senescence have not been accumulating. However bats have natural enemies, and in natural environment bats usually die long before maximum lifespan. This is confirmed by direct observations and, especially, by the fact, that the bat populations increase slowly. In 1950-60s the bat populations declined over the territory around Saint-Petersburg because of inappropriate scientific research (mass sampling, unsuccessful banding and experiments), and they still cannot reach the past condition. The bat longevity is caused by long periods of the inactive condition, slow reproduction rate, little light exposure. Concept of mutations accumulations have to be rejected. The following concept is proposed instead: senescence results from any change in organism, i. e. the changes of an organism are inevitable, are not always healthy, and are possible in definite directions, that is why they become unhealthy in a moment. PMID- 21033371 TI - [Caloric restriction increases life span in sterile and non-sterile D. melanogaster females: systems analysis]. AB - Experiments show that moderate caloric restriction in normal (non-sterile) fruit flies results in the increase of life span. It has been found recently that life span increases under caloric restriction also in sterile Drosophila females. This fact was explained by remodeling of metabolism due to insulin signaling. In this paper a hypothesis is put forward that under caloric restriction in the organism, the energy arrival decreases so that the stationary state must be restored. To achieve this, reproduction is reducing, remodeling of metabolism and the increasing of substrates output from the gastrointestinal tract start. The increase of life span can be just a side effect of these processes. Simulation demonstrates that the experimentally observed life span increasing in non-sterile fly females under caloric restriction can be explained exclusively by the reducing reproduction. PMID- 21033372 TI - [Change of the human health throughout life cycle and the role of medical preventive care in detecting diseases]. AB - 1700 men and women at the age of 50 to 80 years were examined to reveal life periods of highest risk of pathology, as well as the role of medical-preventive help in detecting the diseases. Three critical age periods in the life of those interviewed were identified, namely, 15-29, 40-49 and 60-69 years. The results obtained show that age period 15-29 years is combined with exposure to strong psychosocial pressures leading to development of immune deficiency, which, in turn, facilitates the pathology (treatment requiring surgery). 40-49-year period is peculiar for manifestation of prolonged effects of endogenous and exogenous factors. Diseases of digestive organs in men, and those of urino-genital system in women, cause main surgical interventions during this age period. In 60-69-year period the diseases of urino-genital and digestive systems in men are most common against the background of sharp increase of surgeries in both men and women. The largest number of diseases (77.8% in men and 79.6% in women) was identified during seeking medical assistance in polyclinic. Each fifth disease was detected in a hospital, while share of preventive examinations made 4.9% for men and 3.9% for women. The detection of diseases in men by polyclinics was found to have a marked age-related pattern, whereas the number of diseases detected in women in polyclinics remained unchanged from 40-49 years of age. The main share of diseases detected during preventive examinations occurred in the age group of 40 49 years irrespective of gender (45% in men and 36.1% in women), in hospitals--in the age group of 60-69 years (46.3% in men and 35.7% in women). Almost all diseases of different classes were shown to be detected at initial stages in people under 50 years of age, while in patients aged over 50 quite significant changes were diagnosed. PMID- 21033373 TI - [Neuroimmunoendocrine mechanisms of protective effects of medical rehabilitation in elderly patients]. AB - Physical rehabilitation is the basic method for all programs of medical rehabilitation on different pathologies. Such important diseases as chronic heart failure, diabetes mellitus, chronic pulmonary obstructive disease have the high risk of disability. There is a high motivation to their rehabilitation. These diseases progress in situations associated with immune inflammation. Such signal molecules as tumor necrosis factor (TNF-alpha), interleukins-1,6 (IL-1,6) take part in these processes. The role of medical rehabilitation methods in connection of neuroimmunoendocrinic homeosthasis are described in this article. PMID- 21033374 TI - [Age-related features of immunocompetent cells of human placenta associated with diabetes mellitus]. AB - The immune-competent cells of placenta play the important role in protection of developing fetus against infectious agents; but their dysfunction can lead to development of placental insufficiency that affects health both fetus and mother. The aim of this study was the comparative analysis of presence of immune competent cells in villous chorion of mature placenta, taken from women with diabetes of different age groups. In our study we found three subpopulations of immune cells in villous chorion of mature placenta: natural killer cells (NK), B lymphocytes and macrophages. Prevailing subpopulation are macrophages, they are detected 1,8 times more often than B-lymphocytes, and 2,3 times more often than NK. The quantity of immune competent cells in groups with diabetes of various types is different. Thus, the greatest number of macrophages was detected in group with diabetes type II of middle age (29-35 years)-- 4.62 +/- 0.93%, B lymphocytes in group of women with diabetes type I of younger age (18-28 years)- 2.50 +/- 0.30%, NK-cells in group with diabetes type I of younger age--1.98 +/- 0,42%. Analysis of received data showed the differences in expression of markers of immune cells in women of different age groups, which brings about the conclusion of various reactance of immune system of women with diabetes depending on age. PMID- 21033375 TI - [Effect of calcitonin on the type of alimentary hyperglycemia in rats of different age and sex]. AB - The effect of domestic preporation of pig calcitonin (calcitrin, 1 U/100 g body weight intramuscular) on the dynamics of hyperglycemia evoked glucose load per os (30% solution, 1 ml/100 g) in rats was studied. Initial blood glucose concentration in the males and the females of all age groups (immature--1-2 months, adult--5-7 months, old--20-24 months) was normal. The impairment of glucose tolerance exposed in old males still under control. Calcitonin increased initial glucose concentration and evoked glucose tolerance impairment in rats of all age groups. A more marked impairment of glucose tolerance after calcitonin injection was in immature males than the females. Calcitonin evoked a more significant maximum rise of blood glucose in adult females but the degree and the duration of hyperglycemia were higher in the males (7.9 +/- 0.4 mmol/l, p < 0.05 on the 120-th min and 7.2 +/- 0.4 mmol/l, p < 0.01 on the 240-th min in comparison with 5.5 +/- 0.2 mmol/l under control). Calcitonin injection evoked a marked glucose tolerance impairment in old females and a more significant impairment of glucose tolerance in old males (they had a more high glucose levels during almost all intervals of the investigation). PMID- 21033376 TI - [Lignins of Rhodiola rosea and Serratula coronata: peculiarities of chemical structure and antioxidant properties]. AB - Data on comparative investigations of chemical structure of lignins from medical grassy plants Rhodiola rosea and Serratula coronata lignins were obtained. The NMR and ESR spectroscopy, and functional and element analysis were used. The high antioxidant activity of lignins was shown. Experimental evidence of anti-aging activity of Rhodiola rosea lignin on model objects Drosophila melanogaster were presented. PMID- 21033377 TI - [The protective effect of the amino acids in the action of cytostatic in culture of the lymphoid tissue of young and aged rats]. AB - The effect of the cyclophosphane and amino acids with side charge radicales (basic--lysine, arginine, acid--asparagine and glutamic acid) on the cell proliferation and apoptosis development in lymphoide tissue explants in young rats (at age 3 months old) and old rats (at age 24 months old) was investigated in organotypic tissue culture. All amino acids in concentration of 10(-12) M stimulated proliferation in explants' growth zone of young rats and two amino acids (arginine, glutamic acid)--of old rats. Cyclophosphane in concentration of 1 mg/ml inhibited the explant cell proliferation. A delay of the cyclophosphane inhibitory effect was observed under the combined administration into the culture of cyclophosphane with each of the amino acids having a stimulated effect. Thus, the amino acids can possess a protective effect by action of DNA synthesis inhibitors both in young and old rats. PMID- 21033378 TI - [Development of osteoporosis in prematurely aging OXYS rats]. AB - The early osteoporosis in OXYS rats is the presentation of accelerated senescence and earlier positioned as senile. The present study shows the changes in metabolism detected in OXYS rats in the postnatal period. They lead to the development of osteoporosis in future and may underlie the formation of reduced peak bone mass. 90 males OXYS rats used in this study aged from 10 days to 24 months and the control group consisted of 90 male Wistar rats of the matched ages. No differences in BMD in OXYS and Wistar rats at the age of 10 days and 3 months was revealed. At the age of 10 days the OXYS rats showed the higher by 40% activity of ALH--the marker of osteoblast activity--than Wistar rats; but at the age of 3 months ALH activity in OXYS was lower than in Wistar rats. The peak bone mass and BMD in Wistar rats is formed by the age of 12 months, in OXYS rats already by 6, but it did not reach the level of Wistar. The content of Ca in the blood and bone tissue changes similarly: no difference in young age, but reduces in OXYS rats after 6 months to the background of enhanced Ca excretion in urine. However, changing the mineral composition of bone in OXYS rats did not affect the mechanical strength: the absolute strength of the long bones in OXYS at 12 months was lower than that of Wistar, but at the expense of decrease by 1,7 times the cross-sectional area. We suppose that genetically determined hypoplasia of the bone tissue in OXYS rats is the starts of pathogenetic mechanisms of idiopathic osteoporosis. PMID- 21033379 TI - [ Depression during late period of life: perception of morbidity in elderly residents of St. Petersburg]. AB - This cross-sectional cohort study describes older patients' perceptions about depression and characteristics associated with acceptance of treatments. The majority of the 109 respondents consider depression as disease, which should be treated. Many patients cited affordability as an obstacle and considered self treatment options including alcohol intake for depression control. PMID- 21033380 TI - [Whole body vibration (acceleration) training increases bone mineral density and serum levels of osteocalcin in elderly women]. AB - Hip bone mineral density (BMD) and serum markers of bone turnover during drug (antiresorptic medicaments) and non-drug (acceleration training) therapy in elderly women suffering from postmenopausal osteoporosis has been investigated. The hip BMD measured in elderly women after a 24-week antiresorptic therapy (alendronate) and increased by 2.01%. 24-week acceleration training resulted in 1.56% benefit in hip BMD and also serum levels of osteocalcin (+50%, p < 0.05) significantly increased in postmenopausal women. We have determined that the osteogenic effect of acceleration training is mediated by stimulated bone formation. Our findings suggest that whole body vibration (acceleration) training may be a beneficial technique to prevent and treat osteoporosis. PMID- 21033381 TI - [The electrophysiological characteristic of the brain functional status in liquidators of the consequences of the Chernobyl Nuclear Power Plant accident]. AB - 41 liquidators who had worked in the Chernobyl accident area were examined. All of them had nervous diseases. Both alpha-rhythms disorganization and increase of beta-activity were usually observed in brain cortex sensomotor areas of 41 liquidators as compared with 30 healthy individuals. The majority of patients were characterized by both enhanced reaction to light flashes rhythm assimilation and the decrease of nonspecific and skin-galvanic reactions to the light stimulus. The conclusion is made about the systemic CNS damage in liquidators as compared with healthy individuals. PMID- 21033382 TI - [Age-related features of the mesangial proliferative glomerulonephritis]. AB - This article presents the data of 118 patients (77 men and 41 women) with mesangial proliferative glomerulonephritis, aged 22-70 years. It is concluded that the rate of progression and severity of chronic glomerulonephritis, even within the same morphological form, is determined by age. PMID- 21033383 TI - [Risk factors and features of the course of primary and recurrent myocardial infarction in elderly and aged men]. AB - To study the structure of the risk factors and features of the course of a primary and recurrent myocardial infarction in elderly and old age we investigated 443 patients in the first 48 hours of the disease. Significant prevalence of risk factors was established in men with myocardial infarction in St. Petersburg. In most patients, especially with recurrent myocardial infarction, three or more risk factors were determined at the same time, which indicates a high coronary risk. The most frequently we observed the dislipoproteinemia, arterial hypertension, psycho-emotional stress, heart failure in anamnesis, link of disease to the season of year, the frequency of acute respiratory infections and colds, cardiac arrhythmia in anamnesis, smoking and alcohol abuse. Among the associated diseases, the cholelithic disease, urolithiasis and chronic bronchitis prevailed, especially with recurrent myocardial infarction. In the clinical pattern of disease in the first 24 hours, symptoms of heart failure prevailed. Anginal variant of a recurrent myocardial infarction occurs even less frequently, and symptoms of heart failure are more expressed, especially in prognostically unfavorable patients. PMID- 21033384 TI - [Effect of atorvastatin (liptonorm) on indicators of the lipid spectrum of blood in patients with the metabolic syndrome]. AB - In this work the effects of Atorvastatin (liptonorm) in a dosage of 10 mg/24h during 12 months concerning the basic indicators of a lipid spectrum of blood in the patients with a metabolic syndrome are estimated. We have noticed its positive effect concerning not only the general cholesterol and cholesterol lipoproteid of low density, but also concerning thriglicerol and cholesterol lipoproteid of high density, which confirms its favorable influence on the basic indicators of a lipid spectrum in the patients with a metabolic syndrome. PMID- 21033386 TI - [Post-stroke vascular dementia: risk factors and clinical neuro-imaging features]. AB - To analyze the status of risk factors for post-stroke vascular dementia, 128 patients with post-stroke dementia, aged from 50-79 years, have been studied. A control group included 125 patients, aged 50-79 years, with moderate cognitive impairment after stroke. A coronary heart disease was a significant risk factor for the patients aged from 50-59; coronary heart disease, diabetes mellitus, overweight and hyperlipidemia were significant risk factors for the aged 60-69, diabetes mellitus, overweight and hyperlipidemia were significant risk factors for the aged 70-79. The stroke-related factors were cerebral infarction in left hemisphere, frontal and temporo-occipital infarction, thalamic, basal ganglion; cerebral white-matter lesions. The mathematical model of post-stroke dementia prediction was created for patients with post-stroke moderate cognitive impairment. PMID- 21033385 TI - [Computer morphometry of peripheral blood cells in patients of different age with pneumonia]. AB - The aim of the research was to study blood responses to pneumonia in patients of different age and sex. The subjects of the study were 116 patients with extrahospital bacterial pneumonia (80 men and 36 women). The patients were divided into three age groups: 18 to 44 years, 45 to 59 years, and 60 to 74 years. Almost healthy 16 men and almost healthy 14 women have made the control groups. Computer morphometry of leukocytes of peripheral blood was made to all patients. Various reaction of lymphocytes on a pneumonia in men and women of young and middle age was revealed. Indirect evidences of decrease in level of lymphocytes activation in women of young and middle age at pneumonia development were received. The sizes of lymphocytes in elderly patients with pneumonia do not change comparing with the control groups. Sexual differences in reaction of monocytes to pneumonia are not present. The sizes of monocytes in patients with pneumonia of all age groups decrease at the expense of kernels, which indicate to their accelerated manufacture in a marrow. Absence of increase in cytoplasm to nucleus ratio index in elderly patients testifies a smaller degree of monocytes activation in this group of patients. The trend to reduction of the sizes of neutrophiles speaks of the accelerated division of predecessors' of mature neutrophiles. The increase in cytoplasm to nucleus ratio index of neutrophiles in women with pneumonia of young and middle age comparing with the control group specifies to the big degree of activation of neutrophiles link in these groups. PMID- 21033387 TI - [Modern approaches to correction and prophylaxis of premature aging using adaptogenes of plant origin]. AB - Last years, the big attention is given studying of the methods promoting increase of the immune status of an organism, got under influence of extreme factors, in particular, ionas radiations. In this connection perspectivity of application of laboratory diagnostics for testing a degree of defeat of immune system and application phytoadaptogenes is proved, namely: tinctures of a Panacis ginseng, Schizandrae chinensis, an extract Elaetherococcus for correction of such conditions. PMID- 21033388 TI - [Osteoarthritis and cardiovascular diseases in elderly patients: clinical and pathogenetic interrelationship]. AB - Osteoarthritis (OA) is one of the most common medical conditions in elderly people. This article presents the survey data on a problem of poly-morbidities (co-morbidities) at osteoarthritis. Special attention is paid to a combination of osteoarthritis with cardiovascular pathology, and also the data testifying the association between osteoarthritis and the increased death rate from cardiovascular pathology. On the basis of the literature data analysis a hypothesis about an etiopathogenic interrelation between osteoarthritis and cardiovascular pathology is presented. According to the authors, potential pathogenetic links include a chronic nonspecific inflammation and metabolic infringements. There are also evidences that vascular pathology may initiate and/or worsen the disease progression. The important factors aggravating a current cardiovascular disease in patients with osteoarthritis are: the restriction of physical activities and irrational pharmacotherapy of osteoarthritis clinical symptoms (increased risk of cardiovascular accidents is considered as a class-specific side-effect for all NSAIDs). The authors present the own data on rational pharmacotherapy of patients with osteoarthritis and somatic pathology by means of SYSADOA influencing the disease symptoms and being able to modify structural changes (glucosamine, chondroitine sulphate - ARTRA). PMID- 21033389 TI - [Brain natriuretic peptide detection in patients with chronic heart failure of elderly and senile age]. AB - This article describes the diagnostic possibilities of research of NT-BNP level in blood of the patients of elderly and senile age with congestive heart failure. Statistically significant correlation between BNP concentration and a functional class of heart insufficiency is revealed. Definition of BNP level enables to diagnose differentially the difficult forms of congestive heart failure. PMID- 21033390 TI - [Radiation effect on cosmonauts during extravehicular activities in 2008-2009]. AB - The geometrical model of suited cosmonaut's phantom was used in mathematical modeling of EVAs performed by cosmonauts with consideration of changes in the ISS Russian segment configuration during 2008-2009 and the dependence of space radiation absorbed dose on EVA scene. Influence of spatial position of cosmonaut on absorbed dose value was evaluated with the EVA dosimeter model reproducing the actually determined weight and dimension. Calculated absorbed dose values are in good agreement with experimental data. Absorbed doses imparted to body organs (skin, lens, hemopoietic system, gastrointestinal tract, central nervous system, gonads) were determined for specific EVA events. PMID- 21033391 TI - [Cytogenetic analysis of cosmonaut's blood lymphocytes exposed to low space radiation doses and its place in clinical-physiological health monitoring]. AB - The article discusses the informative significance and pertinence of cytogenetic analysis of peripheral blood lymphocytes to the clinical-physiological investigations of cosmonauts conducted before and after space missions (SM) of varying duration. The authors point out high sensitivity of the technique, relative simplicity and affordability of the analysis of instable chromosomal aberrations including such radiation effect markers as dicentrics and centric rings. Cytogenetic investigation of cosmonauts could be used to estimate ionizing radiation dose, and to predict delayed effects. PMID- 21033392 TI - [Results of measuring neutron dose inside the Russian segment of the International Space Station using bubble detectors in experiment Matreshka-R]. AB - Distribution of neutron equivalent dose both inside and outside the spherical phantom (experiment Matryeshka-R) was determined with the help of dedicated research equipment "Bubble-dosimeter". Equipment is built up from an automatic bubbles counter and 8 bubble detectors of neutrons with energy ranging from approximately 200 keV to 15 MeV. Measurements inside the ISS were made in several 7-day sessions in the period from April 2006 till October 2007 (ISS increments 13 15). According to the bubble detectors on the outside of the phantom, ambient neutron dose H*(10) was equal to 0.1 mSv/d or approximately 20% of the dose from charged particles inside the ISS. In the tissue-equivalent phantom, neutron dose was 1.2 +/- 0.2 times less as compared with the phantom surface which characterized the degree of dose attenuation in cosmonaut's body. PMID- 21033393 TI - [Analysis of polymorphism of bone metabolism genes and evaluation of the risk of osteopenia in cosmonauts]. AB - Densitometry of cosmonauts following long-duration missions shows reduction of bone mineral density (BMD). On the average, post-flight BMD remains within the normal range and the broad variability of individual BMD values sometimes is qualified as local osteopenia. Individual reactions are typed by similarity of amount and rate of BMD loss. At present, analysis of functionally significant polymorphism of bone metabolism genes is the most effective instrument for diagnostics of susceptibility to osteopenia and osteoporosis. The investigation was aimed to analyze polymorphism of genes of vitamin-D and (VDR) and calcitonin (CALCR) receptors, and of collagen-1 alpha-1-chain (Col1a-1) in candidate cosmonauts and cosmonauts returned from 5 to 7-mo. missions. According to the results of analysis, in the majority of cosmonauts rapid BMD loss correlated with TT genotype by VDR gene but not with genotypes Tt and tt and associated with carriage of incomplete s-allele in the Col1a1 gene. Yet, in several instances high BMD loss rates were personified with carriers of VDR gene alleles (homo- and heterozygote states--tt and Tt) and heterozygote by Col1a1 gene (Ss). PMID- 21033394 TI - [Dynamics of changes in bone mineral density and structural organization in cosmonauts following space flight of 6 months in duration]. AB - Microgravity effect on bone tissue of cosmonauts was evaluated following space flights of 6 months in duration. Peripheral quantitative computed tomography (pQCT) was used to determine volumetric bone mineral density (VBMD) and structure of distal parts of the leg and forearm. Changes in VBMD were found to correlate with bone position relative to the vector of gravity. In the forearm, reversible hypermineralization was bound together with compact bone thickening. Reversible osteopenia in the lower leg was accompanied with plausible losses both in compact and trabecular bone. Irrespective of position relative to the vector of gravity, bone microarchitecture tended to reduce the number of trabecules and to increase heterogeneity of the trabecular network. Pre-flight structural dynamics showed a complex character with linear time dependence. PMID- 21033395 TI - [Rna content of gerbil hepatocytes after the flight aboard space platform Foton M3]. AB - The paper compares and contrasts the results of measuring the hepatocyte cytoplasm area and RNA content in 35 gerbils in three series of experiments, i.e. the vivarium control, modeled space flight (synchronous control) and exposure to the factors of 12-d Foton-M3 orbital flight. Central, intermediate and peripheral zones of hepatic lobes were subjected to histological and histochemical analyses to measure the hepatocyte cytoplasm area; the RNA content was determined from the level of cytoplasm basophilia after azure staining. Cytometric and cytophotometric investigations were performed using image analyzer Video-7-Test Morpho. In the vivarium animals, hepatocytes with the largest cytoplasm localized predominantly in the intermediate and central zones of the lobes. Judging from the results of microdensitometry, the RNA content was particularly high in binucleate hepatocytes of the intermediate zone. In the synchronous control, hepatocytes tended to grow in size, in the peripheral zone specifically, whereas RNA content was largely equal no matter hepatocyte topography. After space flight, cytoplasm enlargement transcended this process in the vivarium animals. The cytoplasm RNA content along the entire liver parenchyma made a significant decrease equally as compared with the vivarium and synchronous control animals. PMID- 21033396 TI - [Evaluation of synthetic antidiuretic hormone as a corrective substance following head-down tilt]. AB - Effects of synthesized desmopressin, analog of antidiuretic hormone, and water salt supplement on the renal function and orthostatic stability were studied in 6 normal male subjects after 12-hr. head-down tilt (12 degrees). The combination of water-salt homeostasis normalizing methods was effective in retaining excessive liquid and salts. Moreover, tolerance of the standard 20-min. passive standing test improved significantly. Hence, it was demonstrated that intake of synthetic vasopressin analog combined with WSS counteracted hypohydration of organism due to HDT and improved orthostatic tolerance. PMID- 21033397 TI - [Analysis of the species and quantitative composition of lactobacilli obtained from humans in a 300-day experiment with isolation]. AB - Two hundred and two intestinal lactobacill strains were obtained and studied in a 30-d experiment with chambered human subjects. Species composition of intestinal lactobacilli varied in the course of the experiment. Species of lactobacilli persisting in organism in the period of isolation were identified. PMID- 21033398 TI - [Comparative evaluation of productivity of several green cultures as potential higher plant components of bio-regenerative systems of life support]. AB - Purpose of the investigation was to select, analyze and evaluate green plant species known for assisting resistance to diseases and improving physiological functions in humans, and to test allelopathic compatibility of selected species with basic systems for life support. Nutrient substrates were freshly made soil like substrate (SLS) and clayite. Green cultures were 6 spinach species, 2 lettuces, 2 leaf cabbage species and ruccola. The investigations showed that plant productivity was either equal to or better on freshly made SLS than on clayite; however, the greens accumulated large quantities of nitrate nitrogen. The highest productivity distinguished leaf cabbage; the best antiradical properties was demonstrated by lettuces and the worst, by some spinach species. None of the species displayed a negative allelopathic effect on productivity of the reddish test culture. PMID- 21033400 TI - [Effect of thermal shock on seed resistance]. AB - The work was performed in order to evaluate possible negative effect of high temperatures on biological properties of seeds in space experiment BIORISK-MSN-2. Laboratory experiments showed that seeds possess high enough resistance to extended exposure to high temperatures. Results of studying effects of positive temperatures in the region of 40 to 100 degrees C on biological properties of seeds of 19 species and varieties of higher plants belonging to three different families lead to the conclusion that heat stability of seeds depends on temperature value, period of exposure, species, variety and individual peculiarities of plants. These data can be useful in future interpretation of results of experiment BIORISK-MSN-2. PMID- 21033399 TI - [Combined effect of zeatin and hydrogen peroxide on growth of rape and tomato germs as applied to the conditions of biological life support systems]. AB - Cytokine-regulated growth of germs' roots and hypocotyls was investigated on a background of modeled oxidative outbreak caused by the stress from exogenous hydrogen peroxide. Germs of rape (1-d old) and tomato (56-d old) in Petri dishes with solutions containing substances under study were subjected to 24-48 hour incubation in the dark. Exogenous zeatin inhibited growth; in different tests treatment with H2O2 brought about both acceleration and inhibition of root and hypocotyl growth. The combined use of two substances deformed concentration curves. Hydrogen peroxide concentration of 100 microM without cytokines inhibited growth of tomato root significantly, whereas application of 0.003-0.01 and 0.9 microM of zeatin intensified root growth. The series of zeatin concentration effect curves obtained for rape roots and hypocotyls with gradually increasing H2O2 concentration included the inhibition curve (w/o H2O2), curve with predominant growth stimulation and reliable maximum (1 microM of H2O2), intermediate shape curves (0.3 and 3.3-10 microM). Hence, biological life support systems should be designed with consideration for variability of effects of physiologically active substances under conditions of stress. PMID- 21033401 TI - [Investigation of anti-hypoxic action of 3-hydroxypyridine derivatives in animals with some types of experimental pathology]. AB - Experiments with occlusion of the common carotid artery in mice demonstrated that, unlike mexidol and SK-170, single injection of new derivatives of 3 hydroxypyridine (3-HP) SK-100 and IBKhF-2, and semax have an anti-hypoxic action on the model of acute normobaric hypoxia with hypercapnia. In analogous experiments with rats the distinct anti-hypoxic action was produced by 4 new 3-HP derivatives (SK-100, SK-170, IBKhF-22 at the dose of 100 mg/kg and IBKhF-2 at the doses of 10 and 30 mg/kg--extension of life span by 25-39%), mexidol (100 mg/kg) and reference-class antihypoxant amtisol (30 mg/kg, life span expansion by 19 and 27%, respectively). A series of experiments with rats with acute pancreatitis, a distinct anti-hypoxic action was shown by SK-100, SK-170 at 100 mg/kg and IBKhF at 10 and 30 mg/kg (life span extension by 26-40%), mexidol (100 mg/kg) and amtisol (30 mg/kg) which extended life span by 17 and 22%, respectively. Therefore, SK-100 and IBKhF-2 are potent to prolong life span of equally mice and rats; SK-170 and mexidol were effective only in experiments with rats. PMID- 21033402 TI - [Equipment for biological experiments with snails aboard piloted orbital stations]. AB - To fly biological experiments aboard piloted orbital stations, research equipment was built up of an incubation container, filter system and automatic temperature controller. Investigations included analysis of the makeup and concentrations of gases produced by animals (snails) during biocycle, and emitted after death. Filters are chemisorption active fibrous materials (AFM) with high sorption rate and water receptivity (cation exchange fiber VION-KN-1 and anion exchange fiber VION-AS-1), and water-repellent carbon adsorbent SKLTS. AFM filters were effective in air cleaning and practically excluded ingress of chemical substances from the container into cabin atmosphere over more than 100 days. PMID- 21033403 TI - [Clinostatting effects on neuronal differentiation of embryonic stem cells from mice strain R1]. AB - The model of embryonic stem cells from R1 mice at the stage of embryoid bodies was used to study effects of slow clinostatting on neuronal differentiation with the help of two markers--beta-III tubulin (early differentiation) and MAP2 (late differentiation). As compared with the control, the number of beta-III tubulin positive neurons was found increased and of MAP2-positive neurons--decreased. As regards MAP2- positive neurons, it is concluded that the gravity factors have a specific effect on EB. The beta-III tubulin staining makes possible determination of the total number of neuronal cells at different stages of development. The observed increase in the number of beta-III tubulin-positive neurons may evidence a nonspecific mechanic effect of clinostatting at the EB stage. It was shown that EB cells are particularly sensitive to clinostatting. PMID- 21033404 TI - [Oxygen consumption by resting humans at different Elbrus altitudes]. AB - The purpose of the work was to test experimentally the "hypoxic paradox" of growing or constant oxygen consumption by normal humans exposed to O2-deficient environments. The objective was to perform thorough statistical analysis of O2 consumption at two altitudes above sea level under the conditions of close to basic metabolism, and to develop an analytical expression for adequate description of O2 consumption dependence on altitude above seal level. The investigation was fulfilled in August, 2009 at the altitudes of 2224 and 4200 m on Elbrus flanks with participation of 4 volunteers. It was shown that O2 consumption by resting humans decreases with altitude, i.e. the "hypoxic paradox" is invalid. An analytical expression was proposed to describe change in O2 consumption in the interval of altitudes from 0 to 4200 m above sea level. PMID- 21033405 TI - [Angiogenesis in different clinical phases of chronic myeloid leukemia]. AB - Angiogensis plays the crucial role in growth and dissemination of neoplastic diseases, both for solid tumors and hematopoietic malignancies. Development of the abundant neoplastic vasculature results from an imbalance between pro- and antiangiogenic regulatory mechanisms. The investigation was focused on expression of the main regulatory angiogeneic factors in different phases of chronic myeloid leukemia (CML) and on influence of leukemic cells on the human umbilical vein endothelial cells proliferation. The groups of 29 patients with CML and of 14 healthy controls were enrolled to the study. The expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor, interleukin-8, angiopoetin-1, platelet factor-4, extracellular matrix metalloproteinases (MMP) 2 and -9 as well as tissue inhibitors of metalloproteinases was determined in peripheral blood and bone marrow mononuclear cells with the use of quantitative real-time PCR method and additionally the concentration of VEGF with the flow cytofluorometry. We evaluated the phosphorylation of endothelial mitogen activated protein kinase in human umbilical vein endothelial cells after incubation in CML cells conditioned media, applying Western blot technique. We determined an influence of the leukemic cells on the endothelial cells proliferation with the colorimetric metabolic MTT test. We showed, that in peripheral blood and bone marrow mononuclear cells in CML patients most of the studied factors were increased at the time of CML diagnosis and became lower in remission. In newly diagnosed CML patients an expression of VEGF, MMP-2 and MMP-9 was particularly elevated. In remission, the levels of VEGF and metalloproteinases, specifically MMP-9, were decreased. If failed to achieve remission, the patients presented the elevated expression of most of the investigated angiogenic factors. In the acceleration or blast crisis phase angiopoetin, VEGF and MMP-2 levels were particularly high. We noticed the markedly enhanced human umbilical vein endothelium proliferation after an incubation in CML cells conditioned media, both in the test of mitogen activated protein kinase phosphorylation in endothelial cells and in the metabolic test for the proliferation intensity of endothelium. The differences of an angiogeneic potential found between clinical phases of CML, and the ability of leukemic cells to stimulate endothelial proliferation, point at the significance of neovascularisation in CML pathogenesis. Further studies are necessary to delineate the possibility of the use of angiogenic inhibitors in the treatment of this malignancy. PMID- 21033406 TI - [Quality of life in elderly, terminally ill cancer patients]. AB - In the last few years many researches have emerged in which quality of life of terminally ill patients has been a main focus of attention. Some evaluation methods have been used in elderly population too. Our paper presents results of a study concerning the problem of QL of patients in the terminal state in institutional care for elderly people. The terminally ill over the age 65 were compared with those of the same aged men and women without cancer and those aged 64 and younger suffering from cancer too. Self-assessment of health and QL was compared with objective evaluation of the health state. We hope this study will give the opportunity to make the QL of our patients better and quality of care more effective. PMID- 21033407 TI - [Role of matrix metalloproteinases (MMP) and their tissue inhibitors (TIMP) in nephrology]. AB - Metalloproteinases (MMP) and their tissue inhibitors (TIMP) play a crucial role to keep the balance between the synthesis and degradation of extracellular matrix protein. Balance disturbances of those two systems lead to abnormal tissue remodeling. There is evidence that matrix metalloproteinases activity changes in many pathological conditions, including inflammatory, degenerative disorders as well as tumor progression. Recent investigations indicate that MMPs and TIMPs play a pivotal role in pathogenesis of most of kidney diseases. Studies describing dysregulated activity of MMPs and/or their tissue inhibitors in various experimental and clinical models of kidney disease, including chronic kidney disease, glomerulonephritis, pyelonephritis, diabetic and hypertensive nephropathy, polycystic kidney disease and renal cancer are reviewed. PMID- 21033408 TI - [A variety of aging symptoms experienced by men from groups of different socio economic backgrounds]. AB - The age-specific decline in secretion of androgens and gonadotrophins in men result in negative changes in their libido, and a variety of psychological and neurovegetative symptoms. The purpose of this paper is to describe a diversity of symptoms accompanying male's ageing in relation to their biological status, socio economic background and lifestyle behaviours. The study sample consisted of 2509 men whose age ranged between 30 and 97 years, and who voluntarily completed anonymous questionnaire. The educational attainement, marital status, place of residence, financial situation, physical activity and smoking habit were used to assess demographic and socio-economic status of the studied men. A set of symptoms accompanying male's ageing, were classified as somatic (FOSM) and psychological (POSM). Biological status of each man was assessed using index of physiological reserve (WRF) a criterion of biological age. All computations were run using Statistica 7.1 programme package. The level of significance was set at p < or = 0.05. Men who did not experience somatic and psychological symptoms were more likely to be younger (< 50 years) residents of medium cities. Those who had experienced almost all symptoms were more likely to be from the older group (> 50 years) of single men (including bachelors, widowers and divorced). The findings revealed that variation of somatic symptoms accompanying male's ageing (FOSM) was in 24% explained (R2 = 0.24) by the set of variables: index of physiological reserve (WRF), calendar age, place of residence, smoking habit and financial situation. Whereas that of POSM, was in 26% explained by index of physiological reserve (WRF), place of residence, marital status and smoking habit. The concluding statement should be stated that somatic and psychological symptoms accompanying male's ageing are associated with negative age-related physiological changes in the organism along with negative changes in family and professional lives. PMID- 21033409 TI - [Risk and prophylaxis of venous thromboembolism in the material of 2nd Chair of Surgery JUMC]. AB - INTRODUCTION: Venous thromboembolism (VTE) is one of the most dangerous complication that could occur in patiens treated in surgical ward. Threat is increased due to presence of additional, apart from surgical procedures, risk factors. It is assesed, that approximately 50 000 patients are at risk of VTE yearly in Poland, 20 000 of them develop pulmonary thromboembolism during hospitalisation, which is fatal in 10% of cases. AIM: Aim of the study was to asses presence of VTE risk factors in the group of patients treated in the 2nd Chair of Surgery Jagiellonian University Medical College and to analyse applied prophylaxis. MATERIAL AND METHODS: The study enrolled 170 patients, 89 (52%) females and 81 (48%) males. Average age of the studied group was 57.9. Medical history of all patients was taken with an emphasis on presence of VTE risk factors. It had a form of questionnaire and enclosed questions. Apart from the anamnesis, physical examination was performed. Type of applied prophylaxis was assesed on the basis of medical records. RESULTS: Each patient was charged with 4 risk factors on average. The most common risk factors were: age, surgical procedure lasting longer than 45 minutes, ischaemic heart disease and hipertension. Clinical probability of deep venous thrombosis was assesed according to Wells scale; low: 59% of studied group, intermediate: 41%, high: 0%. Applied prophylaxis included pharmacotherapy, physiotherapy, and mechanical methods (compression). CONCLUSIONS: The most common risk factor that could be changed was duration of the surgery lasting longer than 45 minutes. Pharmacological prophylaxis should be more often complemented by mechanical methods and physiotherapy, especially in group burdened with high risk of VTE. PMID- 21033410 TI - [Usefulness of non-steroid antiinflammatory drugs in patients with ulcerative colitis]. AB - Non specific inflammations of the intestine are the group of chronic disorders, such as ulcerative colitis and Crohn's disease and with episodic aggravation of inflammatory lesions, called active phase and non-active phase, called remission. Non-steroid antiinflammatory drugs (NSAIDS) are one of the most frequently used medications in the World. NSAIDS therapy in ulcerative colitis patients is a very important clinical problem, because of frequent extraintestinal symptoms, such as arthritis, which make patients to take these drugs. But the mechanisms of the NSAIDS influence on the course of inflammatory diseases of inferior part of gastrointestinal tract is still not known. Our results of clinical studies indicated the influence of nonselective and selective COX2 inhibitors on ulcerative colitis activity. However clinical aggravation was detected in 8% of patients treated with conventional NSAIDS and in one person administered selective COX2 inhibitor. Administration of the conventional NSAIDS as well as coxibs, significantly influenced severity of diarrhea. Moreover conventional COX inhibitors increased severity of colon bleeding and endoscopic colon inflammatory lesions in comparison to ulcerative colitis patients, as well not administered NSAIDS as given coxibs. Total patients evaluation involving the intensity of clinical symptoms did not reveal significant differences between examined groups. The above results showed, that the balance between risk and advantages resulting from administration of NSAIDS both, non-selective and selective COX is to be accepted in ulcerative colitis patients in non-active phase. PMID- 21033411 TI - [Neopterin in serum and cerebrospinal fluid in Lyme disease]. AB - BACKGROUND: Lyme disease is a multiorgan disease, caused by spirochetes of Borrelia species. Clinical picture is diverse, borreliosis can affect skin, nervous system, musculoskeletal system and heart. Neopterin is a marker of cytotoxic lymphocytes T activities, it is produced by monocytes/macrophages stimulated with IFNgamma. AIM: The aim of our study was to evaluate the level of neopterin in serum and cerebrospinal fluid in borreliosis and correlate it with the symptoms, markers of inflammation in cerebrospinal fluid (CSF), and serological tests against Borrelia burgdorferi. METHODOLOGY: We have enrolled in the study 39 patients treated for Lyme borreliosis. The level of neopterin in serum was assessed in all patients, among patient with suspicion of neuroborreliosis (n = 33) we assessed the level of neopterin, protein, glucose and chlorium in CSF. RESULTS: The level of neopterin in CSF was lower among patients who were treated due to presence of erithema migrans in their past regarding patients who had never had erithema migrans (p = 0.008). The level of neopterin in CSF was higher (6.6 nmol/l) in patients with the presence of inflammation in CSF versus patients with no changes in CSF (3.8 mmol/l; p = 0.019). There was no correlation between neopterin in serum or CSF and Westernblot test. CONCLUSIONS: Patients with neuroborreliosis who had lymphocytic meningitis had higher level of neopterin in CSF. We suggest the role of neopterin in pathogenesis on neuroborreliosis. Neopterin as a marker of cytotoxic lymphocytes T activities can be useful in borreliosis diagnosis but more studies regarding this problem should be done. PMID- 21033412 TI - [Analysis of Borrelia burgdorferi genostrains among patients with Lyme disease]. AB - BACKGROUND: Lyme borreliosis is a zoonose which can be transmitted to the humans during Ixodes tick bite to the skin. The disease is caused by bacteria- spirochetes of the Borrelia species, classified as Borrelia burgdorferi strain. In Poland Lyme borreliosis is caused by Borrelia garinii, Borrelia afzelii and Borrelia burgdorferi sensu stricto. The presence of Borrelia spielmani was recently reported. MATERIAL AND METHODS: The study included 249 patients diagnozed in University Hospital in Krakow due to suspicion of Lyme borreliosis in 2005-2008. Results of serologic tests against borreliosis were analized using Elisa tests (Mikrogen), positive tests were confirmed using Western blot tests (Biomedica). RESULTS: It was found the high percentage of the antibodies in class IgM, which are important in acute phase of borreliosis, typical for Borrelia garinii, whereas in class IgG it was found the prevalence of protein typical for Borrelia afzellii and Borrelia burgdorferi sensu stricto. It was found the high prevalence of the presence VIsE reacting with IgG antibodies. It was noted the presence of Borrelia spielmani genostrain in Poland. PMID- 21033413 TI - [Underfoot pressure distribution of female patients with obesity and plantar fasciitis]. AB - OBJECTIVE: Estimation of underfoot pressure distribution of female patients with obesity and bilateral plantar fasciitis. MATERIAL: 45 women aged 58 (SD +/- 9.0) with obesity confirmed by BMI (BMI = 38.2, SD +/- 5.1) and hindfoot-related bilateral pain complaints typical for plantar fasciitis. The control group consisted of 50 women with no obesity and pathologies of motor apparatus found. METHODS: Clinical and radiological examination and postural pedobarography. The underfoot pressure was determined at defined foot regions according to modified Blomgren classification. RESULTS: When compared with the control group, patients with obesity had increased pressure within metatarsus, mainly in its lateral part and within anterior part of hindfoot (MT5, MM, LM, T zone). The maximal value of underfoot pressure was 1052 g/cm2 in patients with obesity and 784 g/cm2 in the control group. There were no statistically significant differences found between underfoot pressures and stronger and lesser pain complaints occurring in one patient. CONCLUSIONS: 1) In obese women with bilateral plantar fasciitis increased underfoot pressure mainly in the lateral part of metatarsus and anterior part of hindfoot was revealed. 2) The above changes correlate with feet dysfunction confirmed during the interview and through the physical examination. PMID- 21033414 TI - [Problems of peritoneal dialysis--history and research perspectives]. AB - This paper specifies the peritoneal dialysis problems as a method of renal replacement therapy in a historical perspective. It pointed out to the dynamic development of peritoneal dialysis in the nineties and distinct slump of the presented treatment form at the turn of XXth and XXIst century, despite substantial progress in the dialysis techniques, effectiveness and biocompatibility of the therapy as well as a detailed evaluation of peritoneal function in vivo and in vitro. It showed descriptions and outline of the peritoneal cavity dating from ancient times, 19th-century animal experiments determining essential laws of peritoneal absorption and removal molecules, as well as the first peritoneal dialysis of a man which took place at the beginning of the 20th-century. The technical problems and peritonitis were the fundamental limitations of this therapy employment in this phase of dialysis development. The application of Tenckhoffs catheter and the technique specified as continuous ambulatory peritoneal dialysis was the invention and at the same time, the turning point which decided about the considerable progress of the described method of dialysis in the nineties. In this period, the analyses concerning failures of the peritoneal transport functions and protection of peritoneum during its long-term use as a dialysis membrane dominated. These studies referred to not absolutely biocompatibility factors of the environment of the peritoneal cavity during peritoneal dialysis. Thence, proposed future directions of analyses include researches concerning components of dialysis solution to assure long-term preservation of peritoneal transport functions and its secretory properties. It is not excluded that experiments of applying the newest achievements of regenerative medicine, in the scope of genetic modification and implantation of mesothelial cells will be continued. PMID- 21033415 TI - [Association between smoking and co-morbid psychiatric disorders]. AB - Although it is well-established that there is an association between smoking and co-morbid psychiatric disorders, several issues remain unclear because most studies do not use standardized diagnostic instruments to assess psychiatric disorders and smoking. Recently three candidate genes have been reported to be associated with both cigarette smoking and various psychiatric disorders. PMID- 21033416 TI - [Diagnosis of alcohol abuse]. AB - About fifteen percent of Polish people abuse alcohol and about two percent are alcohol-dependent. Despite the current prevention strategies, alcohol abuse and its patterns- risky and harmful drinking in particular, are still a growing problem. There is an urgent need to improve alcohol abuse detection strategies and its prevention. Early detection of alcohol problems may prevent their further development and progression. The behavioral and clinical features of alcohol abuse are described at first. Then was briefly described short-range (ethanol, acetaldehyde, acetate, methanol, and 5-hydroxytryptophol), mid-range (fatty acid ethyl esters, ethyl glucuronide, phosphatidyl ethanol, and ethyl sulphate), long range (mean corpuscular volume, gamma-glutamyltransferase, aspartate- and alanine aminotransferases, carbohydrate deficient transferrin, acetaldehyde adducts, beta hexosaminidase, sialic acid) as well as other known and less known biomarkers associated with alcohol abuse. Usefulness of the mid-range biomarkers is increasing, since their time of detection (1-7 days) in biological fluids occur between that of the immediate-range and long-range markers. This is the first week of abstinence in which problems caused by alcohol commonly require treatment. PMID- 21033417 TI - [Dermatology of neonatal period--skin diseases undemanding of treatment]. AB - The skin of newborns differs from adult skin in many aspects. It is in the developing age which makes it difficult to fulfill it's correct function. There are diseases which appear in the first month of the infants life and require treatment. Mild local therapy may be administered or extensive moisturization of skin changes. Common mild and easy passing skin syndromes are: vernix caseosa, cutis marmarotta, hyperplasia sebacea, milia, acne neonatorum, erythema toxicum neonatorum, transient neonatal pustular melanosis, and neonatal dermalia pustulosis. PMID- 21033418 TI - [Lyell'a syndrome--two case presentations]. AB - Clinical symptoms of toxic epidermal necrosis (TEN) include massive epidermolysis within skin and mucous membranes. Similar to extensive stage II burns, this may be a life-threatening condition. Patients with TEN are usually treated in specialized burn centers andlor surgery departments. Here we present and discuss 2 case reports of patients with ocular complications of TEN. The aim of this study is to emphasize the necessity of ophthalmic control and treatment during the early and late phase of TEN. PMID- 21033419 TI - [Examining the psychometric properties of a new quality of life questionnaire in migraineurs]. AB - BACKGROUND: The deleterious effect of primary headaches on the sufferers' quality of life (QOL) has been abundantly documented using both generic and headache specific instruments. The currently used questionnaires focus on a limited number of factors and therefore may not be sensitive enough to detect the effect of headache type and headache characteristics on QOL, despite the obvious clinical differences. We have devised a comprehensive questionnaire that may be more sensitive to the burden of headache. OBJECTIVE: To assess the psychometric properties of the new questionnaire on a group of migraineurs. PATIENTS AND METHOD: We studied 117 migraineurs who completed the validated Hungarian version of the SF-36 generic QOL measure and our new, 25-item questionnaire. Reliability was assessed by internal consistency, measured by Cronbach's alpha of all items. Content validity was examined by calculating the correlation of the items with subscales of the SF-36 measure. The correlation of the patients' migraine characteristics with the questionnaire's items was used to assess criterion validity. RESULTS: The questionnaire was quick and easy to administer. The questionnaire demonstrated good reliability, with Cronbach's alpha being 0.893. Content validity was adequate; most "physical" items of the new questionnaire showed significant correlations with the bodily pain and role physical SF-36 subscales and most "psychical" and "social" items were correlated with mental health and social functioning SF-36 subscales. Criterion validity was adequate, with headache severity being correlated with most of the items. DISCUSSION: In this study the new headache-specific quality of life instrument showed adequate psychometric properties. PMID- 21033421 TI - [Devic syndrome--case report, current principles of diagnosis and therapy]. AB - Neuromyelitis optica (NMO, Devic-syndrome) is a rare, relapsing autoimmune disease of the central nervous system, which is distinguished from other demyelinating disorders by a recently identified, specific autoantibody. By demonstrating the anti-aquaporin-4 IgG in the serum, a heterogenous group of syndromes can be defined, called NMO-spectrum. In the future, optical coherence tomography may support this diagnosis besides the clinical features, imaging examinations and presence of serum antibody. Early recognition and treatment can improve clinical outcome even in serious condition. Long-term immunosuppressive therapy is advised to prevent further relapses and to stabilize or improve clinical status. Hereby, we report a case of a 51-year-old woman, under treatment for one and a half years. We summarize the current knowledge about the pathomechanism, diagnostic strategy and therapy of neuromyelitis optica. We review recent findings and the diagnostic value of a new, non-invasive ophtalmological examination, the optical coherence tomography. According to the first results, this method may be helpful in the early differential diagnosis of optic neuritis. PMID- 21033420 TI - [Analysis of antiparkinsonian drug reduction after bilateral subthalamic deep brain stimulation]. AB - BACKGROUND: Bilateral deep brain stimulation of the subthalamic nuclei (STN) is a well-established and cost-effective treatment in advanced PD. OBJECTIVES: To quantitatively analyze the change in use of antiparkinsonian drugs one year after subthalamic deep brain stimulator (DBS) implantation in patients with idiopathic Parkinson's disease (PD). PATIENTS AND METHODS: Eighteen consecutive patients with advanced PD underwent bilateral STN DBS implantation were involved in the study. The stimulation achieved a stable and clear clinical benefit in all of the cases. One year after the implantation, drug usage of patients was analyzed and correlated with the postoperative symptomatic improvement measured by the modified Hoehn-Yahr, Schwab and England, and Unified Parkinson's Disease Rating Scales. Because none of the investigated variables followed the normal distribution, non-parametric Wilcoxon signed-rank, McNemar and Kendell's T tests were applied. RESULTS: Preoperatively, the patients used 12.05 +/- 4.57 tablets a day out of 3.19 +/- 0.97 different antiparkinsonian drugs, which was significantly reduced by deep brain stimulation to the application of 7.00 +/- 2.96 tablets out of 1-3 (1.84 +/- 0.76) drugs (p < 0.001). Meanwhile, the usage of amantadine, MAO-B and COMT inhibitors was also significantly decreased (p < 0.05). The dosage of dopaminerg medication was significantly lowered from 1136 mg to 706 mg expressed in levodopa equivalent dosage (p < 0.001) whereas the UPDRS III also improved by 48.6%. CONCLUSION: Our study is in accordance with previously published international findings that antiparkinsonian medication can be significantly lowered after bilateral STN DBS. Because not only the dosage, but also the applied number of tablets were decreased, it may have resulted in a better compliance and quality of life. PMID- 21033422 TI - [What does aphasia have to do with memory and behavior disorders?]. PMID- 21033423 TI - [Effects of fluorescent labeling on cytotoxic characteristic and cell distribution of nanopolystyrene]. AB - OBJECTIVE: To explore the feasibility that studied with fluorescent labeling nano scale materials cell kinetics. METHODS: At the doses of 500, 250, 125, 63, 32 and 16 microg/ml and at the times of 48, 24, 16, 8, 4 and 1 h , MTT assay was applied to observe the inhibitory effects in BEAS-2B and THP-1 cell lines treated with fluorescent labeling nanopolystyrene and non-labeling nanopolystyrene. Confocal microscopy and transmission electron microscopy were applied to image the translocation of fluorescent labeling nanopolystyrene and non-labeling nano polystyrene into cells. Results The tendency of cell inhibitory rate both in fluorescent labeling nanopolystyrene and non-labeling nanopolystyrene was same, which increase with the dose increase. There were no significant differences in the same dose group for two kinds of materials (P > 0.05). The two kinds of materials were found to enter the BEAS-2B and THP-1 on 1 h, and localized within the cell nucleus on 4 h. CONCLUSION: There were no obvious influence on cytotoxicity and cell distribution for fluorescent labeling . Fluorescent labeling nanopolystyrene could apply to study cell kinetics equal to the same size nanopolystyrene. PMID- 21033424 TI - [Determination of S-phenylmercapturic acid in human urine by HPLC-MS]. AB - OBJECTIVE: To establish the method to determine S-phenylmercapturic acid (S-PMA) in human urine, and the method was actually applied to determine S-PMA concentrations in the human urine from subjects occupationally exposed to benzene. METHODS: After the urine samples are hydrolyzed by acidification, and modulated to suitable pH value. S-PMA is obtained by liquid-liquid extraction and separated by HPLC. Use negative ion mode electric spray ion source MS to measure, and select the molecular ion peak m/z 238 and quantitative analysis is performed by peak area. RESULTS: This method has good linear in the range of 5-320 microg/L, and r = 0.9994 +/- 0.0003, and the detection limit is 1.2 microg/L (S/N = 3), recovery percentage is 86.8%-94.2%. Both the intra- and inter-day precisions are less than 7%. Use this method to measure the S-PMA in the end-of shift urine of 55 workers occupationally exposed to benzene and perform the regression analysis for the S-PMA concentration and the benzene concentration in air (r = 0.8035, P < 0.05). CONCLUSION: The method established by this research is rapid, sensitive and selective, and the results are accurate and reliable. PMID- 21033426 TI - [Study on inducing differentiation of mouse embryonic stem cells into neuronal in vitro]. AB - OBJECTIVE: To investigate the probabilities and properties of embryonic stem (ES) cells differentiating into neuronal cells in vitro by retinoic acid. METHODS: Mouse ES D3 cells were cultured by means of handing drop and suspending on the ES conditioned media for 3 days and 1 day until ES cell aggregations was formed (embryonic bodies, EBs). The EBs were exposed to retinoic acid (RA) for another 4 days. Immunohistochemistry, RT-PCR assay and the fluorescence intensity changes of calcium after Glu stimulation were performed to identify the characteristics and differentiation efficiency of the differentiated cells. RESULTS: Expression of nestin protein was detected by immunohistochemistry after 96 h induction and the nestin positive cells were (53.49 +/- 6.02) %. RT-PCR assay further identified that the induced cells expressed transcripts for neural associated genes including nestin, glutaminase and Brn-3. And the induced cells have the same character with neuronals after Glu stimulation. CONCLUSION: ES cells can be successfully induced by retinoic acid into neuronal cells expressing multiple properties of neurons in vitro, and these cells have the similar characters with the neuronal derived in vivo. PMID- 21033425 TI - [Study on relation between Sp110 gene polymorphism and tuberculosis genetic susceptibility of Chongqing Han People]. AB - OBJECTIVE: To investigate the association of Sp110 gene SNP with tuberculosis occurrence of Chongqing Han people. METHODS: Design Use the case-control study design, and collect risk factors of tuberculosis by questionnaires. Use multiple methods to detect rs1135791C/T, rs722555A/G, 5'-UTR rs11679983A/G, rs28930679C/T, rs9061A/G, rs1063154G/T, rs1047254A/G, rs3948464C/T points SNP polymorphism. Use SAS software to perform significance test. And use MDR software to analyze the cross action of SNP points related to tuberculosis susceptibility. RESULTS: (1) the frequencies of Sp110 gene rs1135791CT genotype, rs722555 GG genotype, rs11679983 GG genotype, rs3948464CC genotype in the case group are significantly higher than those in the control group. (2) Logistic regression analyzes rs1135791C/T, rs722555A/G, rs11679983A/G, rs3948464C/T, smoking history, family with TB, per capita living space and BMI were with relation to tuberculosis. (3) Sp110 gene rs722555A/G has the cross action with 3 points: rs1135791C/T, rs11679983A/G and rs3948464C/T, respectively. CONCLUSION: rs1135791C/T, rs722555 A/G, rs11679983A/G, rs3948464C/T may be the risk factors for susceptibility to tuberculosis in Chongqing Han People. PMID- 21033427 TI - [Effect of diisobutyl phthalate on antioxidase activity and DNA damage in mice]. AB - OBJECTIVE: To investigate the oxidative damage of mice induced by diisobutyl phthalate (DiBP) and the mechanism of free radical oxidative damage caused by DiBP. METHODS: Sixty KunMing mice were divided by weight into 5 groups after accommodation to the experimental animal room for 3 days. The control group and 4 DiBP groups, group I, II, III and IV, were given DiBP in corn oil by gavages at the dosage of 0, 50, 250, 500 and 1000 mg/kg respectively. The mice were fed with normal diets and drinking water freely for 8 weeks. By the end of the experiment, the comet assay of blood and SOD, GSH-Px, MDA and 8-OHdG of liver were tested. RESULTS: The activities of SOD and GSH-Px in DiBP groups were significantly lower than the control group (P < 0.05); the MDA contents of DiBP group III and group IV were significantly higher than the control group (P < 0.05) and the 8-OHdG content of group II was significantly higher than the control group (P < 0.01). The comet assay showed that the oxidative damage of DNA in DiBP groups was significant in comparison with the control group (P < 0.05). CONCLUSION: Oxidative stress induced by diisobutyl phthalate can decrease the activities of antioxidative enzymes and result in oxidative damage of tissues. PMID- 21033428 TI - [Isolation and identification of probiotics from yoghourt in Beijing]. AB - OBJECTIVE: To carry out isolation and the viable plate count of probiotics from yoghourt. To investigate the antimicrobial susceptibility of strains to penicillin, gentamicin, ampicillin, vancomycin, clindamycin and erythromycin. METHODS: Probiotics were recovered and counted from yoghourt by plate count method. The recovered isolates were characterized by Gram's stain, biochemical test, antimicrobial susceptibility test. RESULTS: MRS medium and (36 +/- 1) degrees C were the optimum condition of culture. In total, 52 probiotic isolates were recovered from 31 yoghourt products, 12 (38.7%) products showed a lower probiotic quantity than 1 x 10(6) cfu/ml of the national stantard, and 19 (61.3%) products were higher than 1 x 10(6) cfu/ml. Gram's stain showed that 37 isolates were gram positive bacilli and 15 isolates were positive coccus. These 52 isolates were grouped into six species by biochemical method, including L. bulgaricus, S. thermophilus, L. acidophilus, L. casei, L. delbrueckii and L. fermentum. All 52 isolates were susceptible to penicillin and ampicillin, one isolate was resistant to both clindamycin and erythromycin, four isolates were resistant to vancomycin. CONCLUSION: Most of yoghourt products contained sufficient viable probiotics as required by the national standard. A small quantity of isolates were resistant to some antimicrobials and multi -drug resistant isolates were also found. PMID- 21033429 TI - [Preliminary study on evaluation system of mental workers strain based on primary and middle school teachers]. AB - OBJECTIVE: To use primary and middle schools teacher as samples to preliminarily build the mental work stress effect evaluation system, providing the methological platform for the research on the stress effect mechanism and mental workers interference measures. METHODS: 851 teachers in primary and middle schools were selected with randomly stratified cluster methods. Use ISTA 6.0 and Life Events Evaluation Table to measure the stress factors, and use Work Tension Reaction Questionnaire, Symptom Self-Evaluation Table Questionnaire, and General Happiness Sensing Table to measure psychological stress reaction, blood sugar and blood fat, blood cortical, ACTH, nerve behavior function, for measuring physiological stress reaction. The Comprehensive Working Ability Index Table to measure working ability. And then use the mathematical model to build the mental workers stress effect evaluation system. And apply the simple random sampling method to select 400 environmental protection workers to perform cross effect validation. RESULTS: The model fits relatively well (RMSEA = 0.100, GFI = 0.93, NNFI = 1.00, CFI = 1.00) and conforms with the theory, reflecting the loads of the indice, such as, working stress reaction, psychological stress reaction, physiological stress reaction and working ability, are relatively high. At the same time, the stress reaction of those 4 dimensions can fit the 2-grade factor (stress effect) very well. The physiological stress reaction is negatively correlated (P < 0.05) with the working stress reaction, psychological stress reaction, working ability decrease, while is positively correlated (P < 0.05) with the working stress, psychological stress reaction, physiological stress reaction and working ability decrease. The social support is the protection factor for working stress, psychological stress reaction, physiological stress reaction and working ability decrease (gamma(s) are -0.55, -0.77, 0.73, -0.79, respectively, P < 0.05). While working stress factors, social life stress factors and dangerous individual characters are the risk factors (P < 0.05) for working stress, psychological stress reaction, physiological stress reaction increase and the working ability decrease. The utilization of the environment protection workers further validates this model. CONCLUSION: It conforms with the theory to evaluate the mental workers stress effects from the 4 dimensions, working stress, psychological stress reaction, physiological stress reaction, and working ability. And these 4 dimensions influence each other, and also are mutually different. The working and social life stress factors influence the stress effects with certain degrees. This evaluation model can tentatively be the methodological basis for the mental workers occupational stress evaluation. PMID- 21033430 TI - [Application of risk assessment in process of standards establishment about campylobacter jejuni in chicken]. AB - OBJECTIVE: According to risk assessment results of the Campylobacter jejuni in chicken of Chinese residents' dietary, from the point of the standard management, establish the feasible measures to reduce the risk. METHODS: Half-quantity risk assessment of Risk Ranger was used. RESULTS: Campylobacter jejuni usually could not reproduce in the processing environment or in the processed products of chicken. Currently, the risk of the likelihood that the urban people of our country have Campylobacter jejuni infections due to eating chicken was six times as that of the rural people. CONCLUSION: There is no need to set a limit level for Campylobacter jejuni in the standard of chicken products. Control in the feeding, processing and preparation before eating of chicken are the important measures in reducing the Campylobacter jejuni infections caused by chicken. PMID- 21033431 TI - [Basic metabolic rate of young adults in Shenzhen]. AB - OBJECTIVE: To measure the basic metabolic rate (BMR) of young adults with normal BMI in Shenzhen. METHODS: 25 men and 25 women in hospital were selected according to questionnaire, medical examination, blood test, liver function, nephron function, thyroid gland level, and TSH. Their BMR and resting metabolic rate (RMR) were measured by using the K4b2 in normal circumstances. The BMR values were compared with the calculated results from the Schofield equation (adjusted). The body composition was measured by bioelectrical impedance analysis. RESULTS: The BMR values measured by the K4b2 were 278.54 +/- 45.56 kJ/h (male) and 224.08 +/- 38.24 kJ/h (female). CONCLUSION: The BMR value of Shenzhen young adults measured by K4b2 is a little higher than that of youth in north China. PMID- 21033432 TI - [Effects of pre-pregnancy BMI on blood glucose, blood pressure and weight in pregnancy]. AB - OBJECTIVE: To investigate the effect of pre-pregnancy body mass index (BMI) on blood glucose, blood pressure and body weight during pregnancy in women. METHODS: 600 pregnant women in Beijing Haidian Maternal and Child Health Hospital were followed from 5th, Feb. 2009 to 15th, Mar. 2009 as a cohort study. Height, weight, blood glucose and blood pressure were detected in all the pregnant period. RESULTS: The pre-pregnancy BMI correlated significantly with gestational weight in different pregnancy phases (P < 0.05). The rates of impaired glucose tolerance, diabetes mellitus and hypertension during pregnant in overweight and obesity women are much higher than the rates in low and normal body weight women (P < 0.05). CONCLUSION: The pre-pregnancy BMI is a crucial risk factor of gestational hypertension, gestational high blood glucose and the gestational body weight. To carry out pre-pregnancy health education is an important measure to prevent complications of pregnancy. PMID- 21033433 TI - [Analysis of correlation between insulin resistance, blood lipids and Alzheimer's disease]. AB - OBJECTIVE: To investigate the relationship between Alzheimer' s disease(AD) and insulin resistance and blood lipids. METHODS: Serum samples collected from 45 AD patients and 44 healthy controls were analyzed by automatic biochemical analyzer to detect the levels of blood glucose, insulin, blood lipids. The variables were evaluated statistically by SPSS 11.0. RESULTS: Serum total cholesterol (TC), insulin (INS), insulin sensitivity index (IAI) and body mass index (BMI) from AD patients were significantly higher than those from health controls (P < 0.05), whereas the insulin resistance index (IR) and insulin secretion index (IS) from AD patients were significantly lower than those from healthy controls (P < 0.05). CONCLUSION: The abnormality of blood lipids and insulin might have potentially harmful effects on central nervous system, of which especially the neurotoxic effect on amyloid (Abeta) neurotoxicity and tau protein phosphorylation might result in memory impairment. These suggested that high blood lipids and insulin resistance were probable risk factors of Alzheimer's disease. PMID- 21033434 TI - [Study on effect of 3 types of drinking water emergent disinfection models in flood/waterlog areas]. AB - OBJECTIVE: To establish 3 drinking water emergent disinfection processing models, separated medicate dispensing, specific duty medicate dispensing, and centralized filtering, in flood/waterlog areas, and compare the effects of these 3 models on the drinking water disinfection processing. METHODS: From October to December, 2008, 18 villages were selected as the trial field in Yanglinwei town, Xiantao city, Hubei province, which were divided into three groups, separated medicate dispensing, specific duty medicate dispensing, and centralized filtering. Every 2 weeks, drinking water source water, yielding water of emergency central filtrate water equipment (ECFWE) and container water in the kitchen were sampled and microbe indices of the water sample, standard plate-count bacteria, total coliforms, thermotolerant coliform bacteria, Escherichia coli were measured. RESULTS: The microbe pollution of the water of these 3 water source groups are heavy, all failed. The eliminating rate of the standard plate-count bacteria of the drinking water emergent centralized processing equipment is 99.95%; those of the separate medicate dispensing, specific duty medicate dispensing and centralized filtering are 81.93%, 99.67%, and 98.28%, respectively. The passing rates of the microbe indice of the resident contained water are 13.33%, 70.00%, and 43.33%, respectively. The difference has statistical significance. CONCLUSIONS: The drinking water disinfection effects of the centralized filtering model and of the specific duty medicate dispensing model are better than that of the separated medicate dispensing model in the flood/waterlog areas. PMID- 21033435 TI - [Study of between persistent organic pollutants (POPs) content in children vein blood and thyroid stimulating hormone (TSH) in the capcitors dismantlement area]. AB - OBJECTIVE: To explore, in the capacitor dismantlement area, the exposure level of the PDP (PCB, Dioxin and PBDE) and the discrement situation of TSH in children vein blood. And analyze the correlation between the above 3 polluants and the TSH level in children. METHODS: In 2 places, LuQiao and Long You, 108 and 123 children aged between 6 and 8 were selected to detect the health situation and measure the PCB, DIOXIN, PBDE, TSH levels in the vein blood, and use the SPSS software to get the correlation result between PCB, DIOXIN, PBDE and TSH and the difference of the above measurements in these 2 places. RESULTS: In LuQiao, the PCB, DIOXIN, PBDE, TSH measurements in the children vein blood were 484.00 +/- 84.66 ng g(-1) lipid weight, 26.00 +/- 19.58 ng/g lipid weight, ng/g lipid 664.28 +/- 262.38 weight, 1.88 +/- 0.42 mIU/L; In LongYou, the PCB, DIOXIN, PBD, TSH measurements in the children vein blood were 255.38 +/- 95.12 ng/g lipid weight, 39.64 +/- 31.86 ng/g lipid weight, 375.81 +/- 262.43 ng/g lipid weight, 3.31 +/- 1.04 mIU/L. In both places, the TSH measurements were in the range of normal reference; the correlation differences between PCB, DIOXIN, PBDE and TSH were relatively significant. In Lu Qiao area, the correlations between PCB, PBDE and TSH show relatively strong positive correlation, but DIOXIN and TSH shows slightly weak negative correlation. In Long You area, all of the 3 polluants show relatively strong positive correlations with TSH. There are significant difference TSH levels between except Lu Qiao and LongYou, other all no significant difference. CONCLUSION: PCB, DIOXIN and PBDE, these three kinds of matters have certain effect on the TSH discrement. PMID- 21033436 TI - [Expression and clinical significance of Ran in lung squamous carcinoma tissues]. AB - OBJECTIVE: To investigate the expressions on mRNA and protein levels and clinical significance of Ras-related nuclear protein (Ran) in lung squamous carcinoma tissues. METHODS: Expressional levels of Ran were detected by the methods of real time quantitative PCR and Western Blot consisting of 22 cases of lung squamous carcinoma tissues and adjacent normal tissues with different TNM stages and differentiated degree, then the correlations of Ran expressional levels to pathological characters were evaluated. RESULTS: The mRNA expression of Ran in squamous cell carcinoma tissues was 2.35 times of that in the adjacent normal tissues and the difference was significant (P < 0.05). The expressional level of Ran protein in lung squamous carcinoma tissues was higher than that in the adjacent normal tissues. The expressional level on mRNA and protein in III stage tissues was higher than that of I and II stages in lung squamous cell carcinoma (P < 0.05). The difference of expression level between differentiated degree was not found (P > 0.05). CONCLUSION: The increased expression of Ran in lung squamous cell carcinoma might be correlated with carcinogenesis and used as a supporting marker for early diagnosis of lung carcinoma. PMID- 21033437 TI - [Rapid qualitative analysis of indandione rodenticides by high-performance liquid chromatography coupled with ion trap mass spectrometry]. AB - OBJECTIVE: To establish a method for the simultaneous qualitative analysis of four indandione rodenticides by high-performance liquid chromatography coupled with ion trap mass spectrometry (LC-IT/MS). METHODS: After the indandione rodenticides in bait were extracted by acetone, and cleaned by solid-phase extraction (SPE), the liquid chromatographic separation and the MS/MS cracking were performed in the optimal instrument conditions by LC-IT/MS. Qualitative detection were carried out by the principle of mass spectrometry analysis of three qualitative ions. RESULTS: The MS/MS fragment ions had good characteristics and stability, the cracking ways to the parent ions and fragment ions were clear. Qualitative ion pairs were m/z 339-->167 and m/z 339-->145 for diphacine, m/z 373 ->201 and m/z 373-->145 for chlorophacinone, m/z 229-->145 and m/z229-->187 for valone, and m/z 229-->172 and m/z229-->145 for pindone. CONCLUSION: This established method is simple, accurate and reliable for the qualitative analysis of indandione rodenticides. PMID- 21033438 TI - [Analysis on opioid compounds in the hair of heroin addicts with LC-MS/MS]. AB - OBJECTIVE: To evaluate the effects of washing process on hair samples from heroin addicts, and compare the extracting method of enzymatic digestion with homogenization of hair samples. METHODS: After washing samples for 3.15 h, a mild enzymatic digestion procedure at pH 6.6 and a buffer incubating procedure in water bath at 48 degrees C during 18h was used. The samples were pre-treated by solid phase extraction using mixed mode sorbent columns (MCX Oasis). Quantitative analysis of morphine, codeine, 6-acetylmorphine, heroin, acetylcodeine by chromatography-tandem mass spectrometry method was developed. RESULTS: Heroin accounted for 21.82% of the total equivalents of morphine. The ratio of morphine to 6-MAM in enzymatic digestion hair samples was 0.9875 and that in homogenized hair samples was 0.3948. CONCLUSION: The results suggested that the procedures were not sufficient to remove the contaminants penetrating into hair from external sources. PMID- 21033439 TI - [Rapid detection of Shigella dysenteriae by PCR assay]. AB - Based on the invasive plasmid antigen H gene (ipaH) of S. dysenteriae, one pair of specific primers was designed for PCR assays in this study. The concentrations of dNTP, Mg2+ and primer, dosage of Taq DNA polymerase, annealing temperature and circulating parameter in the PCR amplification system were optimized. In this way, a rapid and stable method of PCR assay for the detection of S. dysenteriae was established. The specificity and sensitivity of PCR were also analyzed. The detection limits of pure culture and genomic DNA in the PCR assay were 1.06 x 10(2) cfu/ml and 106.34 pg/PCR system, respectively. The detection limit for S. dysenteriae in artificially contaminated food samples was 3.21 x 10(4) cfu/ml. These results indicated that the PCR method for S. dysenteriae detection was simple, rapid, high in specificity and sensitivity and suitable for the detection of pathogens in foods caused by Shigella dysenteriae. PMID- 21033440 TI - [Effect of repeated fasting/refeeding on body weight control and energy balance regulation in rats]. AB - OBJECTIVE: To investigate the changes of expression on leptin, a series of neuroendocrine factors and hormones associated with body weight control and energy balance regulation of rats, which were treated with repeated fasting/refeeding and followed by fed with high fat diet. METHODS: Designing a repeated fasting/refeeding rats model (RFR) fed with basic stock diet on repeated cycles of 1 d fasting and 1 d refeeding for 6 weeks. The rats in RFR-LF/ HF group were switched to a high fat diet and fed the diet every day for another 6 weeks. The control rats were randomly divided into 3 groups, control group, high-fat diet (HF) group and common fat diet (CF) group. The rats in HF and CF group were killed by the end of the 12th week. The body weight, Lee's index, body fat content and serum lipid, GH, T4, leptin, insulin, and plasma ACTH levels were measured. The expression of NPY and POMC mRNA in hypothalamus were detected by reverse transcription chain reaction (RT-PCR). RESULTS: The Lee's index, body fat content, serum TC, TG, LDL, leptin and insulin levels of RFR-LF/HF group were lower significantly than those of HF group whereas higher significantly than those of CF group. The expression of NPY mRNA of RFR-LF/HF group were higher significantly than those of HF and CF groups, while the expression of POMC mRNA was lower significantly than that of HF and CF groups. CONCLUSION: The feeding pattern of repeated fasting/refeeding can decrease the degree of obesity induced by high fat diet, and also reduce the leptin and insulin resistance, but cause serious disturbance of the expression of neuroendocrine peptides in the central nervous system of rat. PMID- 21033441 TI - [Some bio-chemical indice change of rats striatum poisoned by rotenone]. AB - OBJECTIVE: To observe some of bio-chemical indice of rats striatum poisoned by rotenone. METHODS: Apply the method of back-implantation mini-effusion pump to observe influence of different concentration rotenone on the rat striatum. Utilize Fluoro-Jade B combined Fluorescent dying to observe the change conditions of the neural cells of the poisoned rat striatum. HPLC is used to measure contents of ATP, ADP, and AMP in striatum. Apply bio-chemical lab to analyze the activities of Na+ -K+ -ATPase and Ca2+ -ATPase. RESULTS: There appeared a large quantity of positive degenerative neurons in the poisoned rats striatum, but the solution control group did not show similar change. Compared with the solution control group, the ATP contents in the rat striatum of the 2.0 mg/kg and 4.0 mg/kg rotenone groups were significantly decreased (P < 0.01), while the contents of ADP and AMP were relatively raised. With the increase of the poison contents, the activities of Na+ -K -ATPase and Ca2+ -ATPase were inhibited to some degrees. The difference has statistical significance. CONCLUSION: Rotenone could cause the decrease of the ATP content and inhibit activities of Na+ -K+ -ATPase and Ca2+ ATPase. PMID- 21033442 TI - [Research on utilization of phage display technology to screen chloramine ketone simulated surface point]. AB - OBJECTIVE: Utilize phage display technology to screen chloramine ketone simulated surface point, providing the basis for establishing drug-free ELISA test system. METHODS: Use the anti chloramine ketone monoclonal antibody as the ligand, and screen the Ph.D. -7(TM) phage display peptide library to select the chloramine ketone simulated surface point. After 4 rounds of screening, select the phase, which can combine the chloramines ketone monoclonal antibody with different degrees, and further, determine the positive clone with competitive inhibition of the hydrochloric chloramine ketone by the indirect competitive ELISA method. RESULTS: It is discovered that all the 10 phages can combine the chloramine ketone monoclonal antibody with different degrees. Use the indirect competitive ELISA method to determine, the phenomenon that 5 positive clones, among them, have competitive inhibition with the hydrochloric chloramine ketone exists. The sequencing results of those 5 positive clones show that 4 different amino acid sequenced are obtained. CONCLUSION: Tentatively judge these 4 phages display the chloramine ketone simulated antigen surface points. PMID- 21033443 TI - [Fermentation of two insoluble dietary fibers by colonic microflora in vitro]. AB - OBJECTIVE: To investigate the rule of insoluble dietary fiber fermentation in intestinal tract. METHODS: Using destarched wheat bran and sugarcane residue as substrates for the fermentation of colonic microflora in vitro in anaerobic conditions. Samples were collected at 0, 4, 8, 12 and 24 h after fermentation, and the pH value, selective plate colony counts were measured and the content of SCFAs were detected with GC. RESULTS: After fermenting for pH 5.43. The change of colony counts of Bifidobacterium, Lactobacillus, Enterococci, Enterobacter, Bacteroides and total anaerobic bacterium was not significant in two media with different substrates at different fermentation periods. Both destarched wheat bran and sugarcane residue could be utilized by colon microbials to produce SCFAs, most of which was propionate at the amount of 0.58 mg/ml and 0.56 mg/ml respectively. During the fermentation process, lactic acid was accumulated and promptly consumed by colonic microflora. CONCLUSION: Insoluble dietary fiber could be fermented by intestinal microflora. The growth succession of colonic microflora might be varied during fermentation. PMID- 21033444 TI - [Influence of fluorine on expression of androgen-binding protein and inhibin B mRNA in rat testis sertoli cells]. AB - OBJECTIVE: To study the influence of fluorine on the transcription level of androgen binding protein (ABP) and inhibin B (INHB) mRNA in testis sertoli cells of Sprague Dawley rats. METHODS: A method was set up the model to culture the Sertoli cells. Use a series of concentrations of NaF solutions of 2.5, 5.0, 10.0 and 20.0 mg/L to poison the cells and then, measure the relative expression amount of ABP and INHB mRNA by RT-PCR method. RESULTS: (1) Compare the relative expression amount of ABP mRNA of each group of different concentration with the control group. 2.5 mg/L group was higher than that in the control group, and the difference has the statistical significance (P < 0.05). The 5.0 mg/L group was also higher than that of the control group, and the difference has no statistical significance (P > 0.05). (2) Compare the relative expression amount of INH B mRNA of each group of different concentration with the control group. Both the 2.5 mg/L group and the 5.0 mg/L group were higher than that in the control group, and the difference has the statistical significance (P < 0.05). The rest 2 groups were lower than that in the control group and the difference has no statistical significance (P > 0.05). CONCLUSION: In the range of concentrations between 2.5 and 20.0 mg/L, no distinct influence of fluorine on the expression of androgen binding protein (ABP) and inhibin B (INHB) mRNA in testis sertoli cells of Sprague Dawley rats. PMID- 21033445 TI - [Analysis on the genotyping of 90 Mycobacterium tuberculosis clinical strains isolated from Ningbo with MLVA]. AB - OBJECTIVE: To investigate the genotyping and distribution pattern of the variable number tandem repeats (VNTR) of Mycobacterium tuberculosis clinical isolates in Ningbo with multiple-locus VNTR analysis (MLVA). METHODS: M. tuberculosis clinical isolates selected from Ningbo randomly were cultured with Lowenstein Jensen medium. The bacteria from which the genome DNA was extracted were collected. The polymorphism of VNTR locus was tested in the DNA sample with PCR respectively. The clustering of genotype was analyzed with BioNumerics. RESULTS: 15 VNTR loci of 90 M. tuberculosis clinical isolates were analyzed respectively. There were obvious polymorphisms of VNTRs. The clustering of genotype showed that these strains could be categorized into 4 gene clusters (I, II, III, IV) and 84 genotypes. 11.1% were cluster I including 10 genotypes, 17.8% were cluster II including 15 genotypes, 65.6% were cluster III including 54 genotypes, 5.6% were cluster IV including 5 genotypes. CONCLUSION: The results showed that there were obvious polymorphisms of VNTRs of M. tuberculosis clinical strains preliminarily. There were at least 4 clusters of VNTR genotype and cluster III was the predominant prevalent strain in Ningbo. PMID- 21033446 TI - [Study on pipe material's influence on chlorine dioxide drinking water disinfection]. AB - OBJECTIVE: To study the pipe material's influence on chlorine dioxide drinking water disinfection. METHODS: 0.8 mg/L chlorine dioxide solution was injected into 5 kinds of pipes respectively, PPR, PVC-U, Steel with Zinc coating, copper and PE pipes. Dipped free from light for 48 hours and the concentrations of chlorine dioxide, chlorite and chlorate were tested from samples taken from each kind of pipe at 1, 2, 3, 4, 5, 6, 12, 24 and 48 hours respectively. RESULTS: Chlorine dioxides decay rates in the water dipping the pipes increase as the dipping time increases and the decay of chlorine dioxide mainly occurs within 6 hours after the dipping. But for different pipe, the influence of decay differs. The consumption of chlorine dioxide of the metal pipes is more than that of the plastic pipes. And with 2 hours after the dipping experiment begins, the concentrations of the chlorite of the copper pipe and of the steel with zinc coating pipe increase quickly and reach the maximum concentration. But then the chlorite concentration decreases greatly. After dipped 24 hours, the chlorite in the water in the pipe can not be detected. For other plastic piples, all the chlorite concentrations in the dipping water increase as the dipping time increase. Compared with the start of the dipping experiment, the chlorate concentration in the dipping water of each pipe has no obvious change. CONCLUSION: The material of the water transportation pipe does have influence on chlorine dioxide drinking water disinfection. PMID- 21033447 TI - [Correlation and toxicological significance between myelin protein zero and peripheral nerve disease]. AB - Myelin protein zero (P0) is the major structural element of peripheral myelin that plays a very important role in maintaining the stability of myelin. Recently, many researches find that the structure, distribution and function of P0 have transcended people's early understanding. In this review, the basic features of structure, distribution and function of P0 and its current research advances in neurotoxicology are simply summarized. PMID- 21033448 TI - [Use of threshold of toxicological concern for chemical substances safety assessment]. AB - The threshold of toxicological concern (TTC) approach is a risk assessment tool of toxicology. When the exposure dose of human body is below the TTC of chemicals, the likelihood of that chemical causing negative influence on the human health is very low. Earliest, TTC approach was used in the risk assessment of in the respect of the food packing materials. Currently, TTC approach is used for safety assessment in the fields of food packing material, flavoring agents, medicine, industry chemicals, cosmetics, and etc. TTC approach provides useful assessment tool for the safety evaluation for the chemical substances. PMID- 21033449 TI - [Lead exposure markers and related susceptibility genes based on different people]. AB - Lead (Pb) is a toxic heavy metal which exists widely in the environment. Children, pregnant women, the elderly, and other populations, have diverse ways of lead exposure and different toxicokinetics. Moreover, the exposure and effect of lead involve multiple metabolic pathways and mechanisms. Besides ALAD, VDR, HFE genes, the polymorphisms of TF gene and oxidative-stress related genes (Rac2, GPx1, XDH) have been discovered recently to affect lead internal exposure level as well. This review comprehensively describes the characteristics of lead exposure, metabolic characteristics and the lead exposure sensitive markers, of different people groups, and looks forward to the future of the application of Genome-Wide Association Study (GWAS) in this field. PMID- 21033450 TI - [Research development on disinfection technology for viruses in drinking water]. AB - With the deterioration of water source pollution, the quality requirements for drinking water of countries will become stricter and stricter, and the microbe index has been one of the important aspects. The introduction of the virus index and the development of disinfection technology focusing on virus have significant importance for the improvement of the drinking water standards and for the protection of people health in every country. To be familiar with the domestic and abroad research development of the disinfection control technology focusing on virus provides certain theory guidance and technological support for continuously improving drinking water standard in our country and for establishing safer drinking water processing technologies. So, this article will comprehensively describes 4 aspects: resistance comparison of virus over every disinfection technology, influential factors of disinfection, research development of new technology, and the mechanisms. PMID- 21033452 TI - [Circulating endothelial progenitor cell and its application]. AB - Endothelial progenitor cells (EPCs) have the capacity to proliferate, migrate, and differentiate into mature vessel endothelial cells, but have not yet expressed into the mature vessel endothelial cell type, and have not formed to be the precursor cell of the blood vessels. For those EPCs existed in the peripheral blood circulation in human, known as circulating endothelial progenitor cells (CEPCs), participating in the vascular neogenesis after born and repairing process after endothelial injury. It has become a hot spot of the research on the cardiovascular diseases and other involving endothelial injury. This article comprehensively describes the bio-characteristics of EPCs, the factors influencing the number and functions of EPCs, and the newest research progress in the actual applications of EPCs, providing the new thoughts and new approach for the diagnosis and therapy of cardiovascular diseases. PMID- 21033451 TI - [Some research development on non-small cell lung cancer genetics and genetic expression]. AB - Non-small cell lung cancer is the major cancer causing death among the malignant tumors. Early detection non-small cell lung cancer can detect the patients in time and get the treatment in time, to obtain the relative good therapy results. So, it is necessary to develop a method being able to accurately determine the non-small cell lung cancer at the early stage. Currently, the lung cancer marker detection is of certain importance in the non-small cell lung cancer diagnosis. Large volume of molecular biology research demonstrate that gene polymorphism is the important factor of the lung cancer occurrence. Furthermore, the importance of genetic expression changes that occur during lung cancer development has been realized gradually. In the future non-small lung cancer research, a comprehensive method combing epidemiological, genetic and genetic expression research seems very important. PMID- 21033453 TI - [Evaluation of a protocol for predicting difficult airway in routine practice: interobserver agreement]. AB - OBJECTIVES: To evaluate a protocol for routine assessment of potential risk factors for difficult airway intubation in an anesthesia department, by measuring interobserver agreement and the behavior of the factors in a predictive model. MATERIAL AND METHODS: A cross-sectional study group of 320 consecutive patients undergoing major surgery requiring orotracheal intubation was assessed for possible difficult airway. We calculated interrater agreement for recording of the Mallampati score, thyromental distance less than 6 cm, thick neck, kyphosis, small mouth, macroglossia, and dental prosthesis during the preanesthesia examination (by an anesthetist) and on the day of the operation (by an anesthetist and a resident). We constructed a model to predict difficult intubation (requiring 3 or more attempts). RESULTS: The kappa indices of agreement between the anesthetists at the preoperative examination and in the operating room or the resident were all less than 0.6. Factors like thyromental distance, small mouth, and kyphosis had kappa indices less than 0.21. The kappa index between the resident and the anesthetist in the operating room was over 0.55. The only factor that had a different level of agreement was the presence or not of a dental prosthesis. None of the studied individual factors, nor these factors in association with the Mallampati score, achieved significance in a bivariate regression model to predict difficult intubation. CONCLUSIONS: There is poor interobserver agreement on factors for predicting difficult airway in comparisons between preoperative and operating room assessment by an anesthetist or a resident. The individual predictive factors and their association with the Mallampati score did not prove useful for predicting difficult intubation. PMID- 21033455 TI - [Structure of the arachnoid layer of the human spinal meninges: a barrier that regulates dural sac permeability]. AB - OBJECTIVES: Drugs injected into the epidural space are known to penetrate the subarachnoid space by simple diffusion through the dural sac. We aimed to study the cellular ultrastructure of the arachnoid membrane and the type of intercellular junctions responsible for creating the barrier that regulates the passage of drugs through the dural sac in humans. MATERIAL AND METHODS: Fourteen tissue samples of arachnoid membrane were taken from 2 patients during procedures that required opening the lumbar dural sac. The samples were treated with glutaraldehyde, osmium tetroxide, ferrocyanide and acetone, and then embedded in resin. Ultrathin sections were stained with lead citrate for examination by transmission electron microscopy. RESULTS: The arachnoid membrane was 35 to 40 microm thick. The outer surface contained neurothelial cells (dural border cells) along the subdural compartment, while the internal portion was made up of a plane 5 to 8 microm thick with 4 to 5 arachnoid cells overlapping to form a barrier layer. The intercellular spaces on this plane were 0.02 to 0.03 microm wide; the arachnoid cells were bridged by specialized junctions (desmosomes and other tight junctions). CONCLUSIONS: Structural features of the arachnoid cells provide a barrier within the human dural sac. They occupy only the internal portion of the arachnoid membrane. Specialized intercellular junctions explain the selective permeability of this membrane. PMID- 21033454 TI - [Oral ketamine-midazolam premedication of uncooperative patients in major outpatient surgery]. AB - BACKGROUND: Currently, ketamine is not often used as an anesthetic. Its clinical characteristics and mechanism of action largely depend on antagonism of the N methyl-D-aspartate receptor. OBJECTIVE: To evaluate the utility of oral ketamine as a preanesthetic agent to lower surgical stress for patients with mental disability. MATERIAL AND METHODS: Observational, retrospective study of 112 mentally disabled patients undergoing major dental surgery on an outpatient basis. The study group received oral midazolam, ibuprofen, and 6 mg/kg of ketamine; the control group received only midazolam and ibuprofen. We recorded data concerning demographics, anesthesia, surgery, physiologic variables, Glasgow score, time of onset of anxiolysis, duration of stay in the recovery ward, and adverse events. RESULTS: Conservative odontologic treatment was provided in 66.3% of the cases. Seventy-one patients (64.4%) were in the control group and 41 patients (36.6%) in the study group. Hemodynamic, respiratory, and neurologic changes were minimal and there were no significant between-group differences. Level of sedation differed significantly between groups (P = .001) at 15 and 30 minutes; differences were also observed within the study group. Mean (SD) duration of surgery was 72.6 (29.7) minutes. Mean duration of stay in the postoperative recovery ward was 140.9 (52.1) minutes (135.8 [54.89] minutes in the study group and 144.2 [50.5] minutes in the control group). The incidence of adverse events did not differ significantly between groups. CONCLUSIONS: Oral ketamine is an effective premedication for major ambulatory surgery and does not increase the incidence of side effects. PMID- 21033456 TI - [Ultrasound-guided puncture: applications in a chronic pain clinic]. AB - Ultrasonography provides an excellent tool for the real-time visualization of peripheral nerve structures in regional anesthesia. Techniques are enhanced further when the progress of the needle and diffusion of the anesthetic can be observed. In a chronic pain clinic, ultrasound-guided puncture offers the advantages of accurate images of structures where pain arises: muscles, fascias, tendons, periostea, and joint structures. Visualization also helps the anesthetist to keep the needle away from structures (eg, the esophagus, pleura, vessels or peritoneum) that might lie near the target site. Unlike fluoroscopy, which produces radiation that is potentially dangerous for both patient and health care staff, ultrasound imaging is not harmful. Disadvantages are poor quality images of structures at a certain depth, acoustic shadows from bone structures that block the view of underlying tissues, and poor transport of ultrasound waves by air. Our aim is to describe a series of techniques for ultrasound-guided puncture and the results obtained on applying them weekly for 12 months in a chronic pain clinic. PMID- 21033457 TI - [Postoperative nausea and vomiting and opioid-induced nausea and vomiting: guidelines for prevention and treatment]. AB - Postoperative nausea and vomiting (PONV) causes patient discomfort, lowers patient satisfaction, and increases care requirements. Opioid-induced nausea and vomiting (OINV) may also occur if opioids are used to treat postoperative pain. These guidelines aim to provide recommendations for the prevention and treatment of both problems. A working group was established in accordance with the charter of the Sociedad Espanola de Anestesiologia y Reanimacion. The group undertook the critical appraisal of articles relevant to the management of PONV and OINV in adults and children early and late in the perioperative period. Discussions led to recommendations, summarized as follows: 1) Risk for PONV should be assessed in all patients undergoing surgery; 2 easy-to-use scales are useful for risk assessment: the Apfel scale for adults and the Eberhart scale for children. 2) Measures to reduce baseline risk should be used for adults at moderate or high risk and all children. 3) Pharmacologic prophylaxis with 1 drug is useful for patients at low risk (Apfel or Eberhart 1) who are to receive general anesthesia; patients with higher levels of risk should receive prophylaxis with 2 or more drugs and baseline risk should be reduced (multimodal approach). 4) Dexamethasone, droperidol, and ondansetron (or other setrons) have similar levels of efficacy; drug choice should be made based on individual patient factors. 5) The drug prescribed for treating PONV should preferably be different from the one used for prophylaxis; ondansetron is the most effective drug for treating PONV. 6) Risk for PONV should be assessed before discharge after outpatient surgery or on the ward for hospitalized patients; there is no evidence that late preventive strategies are effective. 7) The drug of choice for preventing OINV is droperidol. PMID- 21033458 TI - [Analysis of the report on the commom health sciences training requirements]. PMID- 21033459 TI - [Anesthesia in a patient with Ellis-van Creveld syndrome]. AB - Ellis-van Creveld syndrome is a rare type of developmental chondroectodermal dysplasia. We report the case of a 32-year-old woman with this syndrome who was scheduled for cesarean section. She had no related heart defect. A spinal block was attempted but after confirming that no sensory blockade had been achieved, general anesthesia was administered. Both the operation and the anesthetic procedure were without complications. The clinical manifestations of Ellis-van Creveld syndrome are short-limbed dwarfism, postaxial polydactyly, fingernail dysplasia, cleft palate and lips, and heart defects. Diagnosis is based on clinical manifestations and radiography. Treatment involves correction of heart defects and orthopedic problems. Perioperative airway management problems may develop. A preoperative echocardiogram should be done to assess heart function and ascertain anatomical abnormalities. Thoracic deformities may make mechanical ventilation difficult and there is risk of barotrauma. Intraoperative management requires rapid control of the airway and prevention of bronchial aspiration. Vigilance in preventing hemodynamic instability and myocardial depression is essential. Postoperative analgesia must be managed carefully and adverse cardiorespiratory events avoided. PMID- 21033460 TI - [Placement of a bronchial blocker through the I-gel supraglottic airway device for single-lung ventilation: preliminary study]. AB - To describe the use of the I-gel supraglottic airway device when placing a bronchial blocker for single-lung ventilation, as applied in a preliminary study to explore the feasibility of adopting the technique with appropriate, selected patients undergoing certain thoracic surgery procedures. We used the technique for single-lung ventilation in 25 patients who required isolation of a lung for a variety of thoracic surgical procedures. A bronchial blocker was placed under direct visualization through a fiberoptic bronchoscope and the I-gel supraglottic device. The I-gel mask allowed us to establish a reliable, safe seal of the airway. For an anesthetist with sufficient experience in managing a flexible fiberoptic bronchoscope, it was possible to carry out all procedures without remarkable anesthetic or surgical events. Single-lung ventilation achieved by introducing a bronchial blocker through the I-gel supraglottic device can facilitate safe, effective management of selected patients who must undergo certain thoracic surgery procedures. PMID- 21033461 TI - [Preexcitation syndrome in a boy during anesthetic induction]. PMID- 21033462 TI - [Comment on the article "Use of a metal guide in the working channel of a fiberoptic scope to insert a tracheal tube in an infant with Treacher Collins syndrome and choanal atresia"]. PMID- 21033463 TI - [Further considerations on the posterior lumbar plexus block in hip surgery]. PMID- 21033464 TI - [Awake patient with a difficult airway: intubation with the AirTraq laryngoscope]. PMID- 21033465 TI - [Cervical dislocation at the C6-7 vertebrae]. PMID- 21033466 TI - [Influence of pneumoperitoneum on the capnography curve: the castle tower waveform]. PMID- 21033467 TI - [Screening of potential antibiotics, inhibitors of the nonmevalonate pathway of isoprenoid biosynthesis--2-C-methyl-D-erythritol-2,4-cyclodiphosphate derivatives]. AB - The recently discovered nonmevalonate pathway of isoprenoid biosynthesis is a prospective target in screening of new antibiotics. Because of the absence of the pathway in the animal cells, the specific inhibitors of the pathway will be a new class of antibiotics against many pathogens (which cause, e.g., malaria, tuberculosis, etc), combining high efficiency and low toxicity. Several derivatives of 2-C-methyl-D-erythritol-2,4-cyclodiphosphate (MEC) were synthesized. 4-Phospho-methyl-D-erythritol-1,2-cyclophosphate, benzyl ether and benzyliden derivative of MEC inhibited the 14C-MEC incorporation into isoprenoids of chromoplasts from red pepper with IC50 of 1.7-5 MM. Some inhibition (about 10%) was also observed with the use of dimethyl ether and isopropyliden derivative of MEC. PMID- 21033468 TI - [Antibacterial susceptibility/resistance of Vibrio cholerae eltor clinical strains isolated in the Caucasus during the seventh cholera pandemic]. AB - The data on antibacterial susceptibility and resistance of Vibrio cholerae eltor phenotypes with different sets of the susceptibility or resistance markers conditioning the outbreaks and sporadic cases of cholera in the Caucasus within 1970-1998 are presented. An increase of the number of the Vibrio cholerae phenotypes resistant to tetracycline and chloramphenicol usually used in the treatment of cholera was recorded in 1990-1994 vs. 1970-1989. The El Tor cholera vibrios stored on synthetic media lost some of their resistance markers, therefore the retrospective investigation of the antibioticograms was only of approximate prognostic value in the choice of the drugs for the etiotropic treatment of cholera in view of possible outbreak of the disease. PMID- 21033469 TI - [Modification of antibiotic resistance in microbial symbiosis]. AB - In antibiotic therapy it is necessary to use drugs active against the pathogen in its association with the host normal microflora. The aim of the study was to investigate modification of antibiotic resistance under conditions of the pathogen association with the representatives of the host normal microflora and to develop the microbiological criteria for determining effectiveness of antibacterials. Modification of microbial antibiotic resistance was investigated in 408 associations. Various changes in the antibiotic resistance of the strains were revealed: synergism, antagonism and indifference. On the basis of the results it was concluded that in the choice of the antibiotic active against Staphylococcus aureus and Streptococcus pyogenes the preference should be given to oxacillin, gentamicin and levomycetin, since the resistance of the pathogens to these antibiotics under the association conditions did not increase, which could contribute to their destruction, whereas the resistance of the normoflora increased or did not change, which was important for its retention in the biocenosis. The data on changeability of the antibiotic resistance of the microbial strains under the association conditions made it possible to develop microbiological criteria for determining effectiveness of antibiotics in the treatment of inflammatory diseases of microbial etiology (RF Patent No. 2231554). PMID- 21033470 TI - [Glutoxime--an inhibitor of multiple drug resistance phenotype associated with Pgp expression]. AB - Interaction of Glutoxime with P-glucoprotein (Pgp), a multiple drug resistance marker, as well as the Glutoxime impact on doxorubicin intracellular accumulation were investigated. It was shown that the Glutoxime effect on the Pgp expressing tumor cells resulted in a decrease of the cell specific fluorescence intensity, conditioned by binding of the monoclonal antibodies to the transport protein. That was evident of Glutoxime competition with the monoclonal antibodies for binding to Pgp and indicative of the modificator interaction with the transport protein. The effect was proved with the use of two cultures of human tumor cells of different histogenesis, i.e., the cells of Jurkat T-cellular leukemia and nonsmall cell lung cancer A549. Inhibition of the Pgp functional activity by Glutoxime was also demonstrateds. The authors suggested that it could be caused by direct competition of the modificator with the antitumor agent for binding to the precipitation sites on Pgp. Glutoxime could be considered as an inhibitor of multiple drug resistance associated with the Pgp function. PMID- 21033471 TI - [Protective activity of Ingavirin in experimental lethal influenza due to pandemic influenza virus A (H1N1)v in albino mice]. AB - Despite obvious success in the vaccine development and chemotherapy of influenza, it remains a poorly controlled infection leading to emergence of new pandemic variants of the virus with high morbidity and mortality. We investigated the protective activity of Ingavirin against the lethal influenza A (H1N1) 2009 virus infection on albino mice. Oral use of Ingavirin resulted in sharp decreasing of the mortality (index of protection up to 57%), slight decreasing of the infectious titer of the virus in the lungs (up to 40-fold), normalizing of the body weight dynamics and the lung tissue structure vs. the placebo-treated control. The degree of the bronchial epithelium damage was also strongly decreased. The results allow to consider Ingavirin as an effective antiviral against the current pandemic influenza virus. PMID- 21033472 TI - [In vivo efficacy of Ingavirin against pandemic A (H1N1/09)v influenza virus]. AB - Ingavirin was shown to be efficient in inhibition of the pandemic influenza virus strains A/California/04/2009 (H1N1)v, A/California/07/2009 (H1N1)v, A/Moscow/225/2009 (H1N1)v and A/Moscow/226/2009 (H1N1)v. as well as the influenza virus strain A/Aichi/2/68 (H3N2) in the lungs of the infected mice. After oral administration of Ingavirin the titers of the influenza virus strains in the lung homogenates lowered. PMID- 21033473 TI - [Characteristics of atypical forms of staphylococci (SCVs) isolated from patients with osteomyelitis]. AB - Small-colony variants (SCVs), isolated from a population of the parental strains of Staphylococcus aureus, S. haemolyticus and S. epidermidis lost a number of features typical of the species and genus and were characterized by delayed growth, altered colony morphology, lack of pigmentation and changed carbohydrate consumption. Some SCVs of S. aureus had no plasmocoagulase and lecithinase activities. The analysis of 14 SCVs showed that they were auxotrophic for hemin and menadione and resistant to aminoglycoside antibiotics. Such aberrant phenotypic characteristics complicated or made it impossible their identification by the common clinical laboratory methods. The tRNA intergenic spacer length polymorphism analysis was used to identify the atypical forms of the staphylococci. PMID- 21033474 TI - [Correction of immunity disorders, treatment of intestinal infections and disbiosis in children (clinical review)]. AB - Acute viral and bacterial intestinal infections in children provoke the Tn2 immune response, resulting in development of severe and complicated forms of the disease and sustained by the disbiotic disturbances due to unnecessarily prolonged use of antibacterial drugs. Cycloferon, an early inductor of interferon 1 and -2, was shown to be safe and efficient in the complex therapy of the intestinal infections. It promoted generation of the Th2 immune response and decrease of the repeated isolation of the pathogen with normalization of the disease clinical signs. The host intestinal microflora was normalized and the level of the opportunistic organisms decreased. PMID- 21033475 TI - [Rational pharmacotherapy and correction of immunity disorders in children with chronic hepatitis (clinical review)]. AB - The data on the efficacy of antivirals and their impact on the virologic and immunologic indices in HCV- and HBV-infected children are presented. The best therapeutic effect in the management of children with chronic virus hepatitis was provided by combined antiviral therapy of different action. In the treatment of babies the drugs of choice could be viferon or cycloferon, for the 2-year older children with chronic hepatitis B the combination of viferon + cycloferon should be recommended and for those with chronic hepatitis C the combination of interal + cycloferon could be used. The cycloferon combination with interferons-a makes it possible to generate the Th1 cellular immune response, to minimize the side effects of interferons and chemotherapeutics and to improve their tolerability. The complex therapy of patients with chronic hepatitis B and lambliasis, using cycloferon and macmiror, provided stable effect, less frequent relapses oflambliasis and minimum side effects of the specific therapy. The repeated isolation of lamblia within a 1-year observation period was recorded only in 16.6% of the children treated with cycloferon vs. the control (40.0%). PMID- 21033476 TI - [Methods for laboratory identification of sepsis pathogens]. PMID- 21033477 TI - [Save the AP-HP museum!]. PMID- 21033478 TI - [Nanomedicine: small size, big stakes]. PMID- 21033479 TI - [Piriformis syndrome]. AB - Sciatic pain is often misleading and establishing the link with a local muscular cause can be difficult and lead to errors, especially when faced with a young sportsman, with typical discogenic pain. Simple, specific and reproducible tests enable a better identification and treatment of a muscular cause or canal syndrome. Physiotherapy, or local infiltrations are generally very efficient, and sufficient. Surgery may be considered only in a very limited number of cases, lack of response to the first line treatment and then only if it is the absolute diagnosis, diagnosis which must remain a diagnosis of exception, more so of exclusion. PMID- 21033480 TI - [Splenic infarction]. PMID- 21033481 TI - [Heart failure. An epidemiological challenge, but a lot of progress]. PMID- 21033482 TI - [Epidemiology of heart failure]. AB - Heart failure is a common pathology sometimes considered as a "new epidemic". Its prevalence is increasing over the years since the cardiovascular management of patients is improving, and the Western population is aging. Prevalence is estimated to 9% in the 80-89 year-old patients, with a mean age of 75 at the onset of heart failure. The proportion of "diastolic heart failure" is about 40 to 55% of the total number of heart failure patients. Hypertension and ischemic cardiomyopathy are the most frequent aetiologies, but diabetes plays an increasing role. Prognosis of heart failure remains poor. Thus, five-year mortality rate is decreasing but remains higher than 50% in recent years. Furthermore, heart failure leads to more than 150 000 hospitalizations in France and the the cost of heart failure represents 1% of the total health expenditures. Thus, heart failure is a major and growing health problem. To reduce morbidity and mortality, we need to optimize therapy (both, pharmacologic and device therapy) and improve preventive measures, such as educational programs and multidisciplinary management in order to treat not only the disease itself but its aetiology, as well. PMID- 21033483 TI - [Pathophysiology of heart failure for clinicians]. AB - Heart failure is the common and final pathway of all the cardiovascular diseases. Its pathophysiology has progressed during the last 20 years; although the inotropy was the main target in the 80', new paradigms have emerged such as remodelling, neurohormonal activation, and more recently desynchronisation...these new concepts have led to substantial therapeutic improvements. However, heart failure remains a severe disease with a high mortality. New therapeutic advances will be possible only by the discovery of new molecular pathways, which could represent a pharmacological target or a target for gene therapy. PMID- 21033484 TI - [Diagnosis of heart failure]. AB - The diagnosis of heart failure is based on strict process using clinical examination as well as other tests. The fine analysis of cardinal symptoms - tiredness and dyspnea--as well as of various signs is required. In cases of uncertainty, blood testing of BNP or NT-pro-BNP improves the diagnostic accuracy. Then the diagnosis is confirmed only after the assessment of evidence of cardiac abnormalities, using cardiac echography among others. Such process will be repeated in cases of significant changes in symptoms. The diagnostic process is associated with etiological investigations as well as the strict assessment of precipitating factors, because of their potential consequences on treatment. PMID- 21033485 TI - [Role of BNP in heart failure diagnosis]. PMID- 21033486 TI - [Stress testing in heart failure patients]. PMID- 21033487 TI - [Role of MRI in diagnosis of heart failure]. PMID- 21033488 TI - [Diastolic heart failure]. PMID- 21033489 TI - [Non-medical and non-instrumental therapy in heart failure]. AB - Chronic heart failure is a disease justifying the initiation of a medical treatment, of which the well-established modalities require cooperation between the general practitioner and the cardiologist. However, this chronic disease also requires patient's active participation in their own treatment, especially through the adoption of new health behaviors: self-monitoring of progression signs, following nutritional recommendations, maintaining adequate physical activity and taking a medical treatment, which may be associated with side effects. Therapeutic education programs or cardiac rehabilitation can help patients to develop these new skills. The management of patients with chronic heart failure involves as well a specific care organization, and in certain cases, a collaboration with specialized multidisciplinary teams providing education, care coordination and long-term supportive care. The social and psychological management of these patients also contributes to the improvement of their quality of life. PMID- 21033490 TI - [What about the European guidelines?]. PMID- 21033492 TI - [Electrical treatment in heart failure]. PMID- 21033491 TI - [Medical management of chronic systolic heart failure]. AB - Medical management of systolic heart failure is standardized and based on international guidelines. They promote the use of combination therapy based on neurohormonal blockade targeting both the renin-angiotensin system (with ACE inhibitors or ARB) and sympathetic nervous system (i.e., beta blockers). Drugs have to be titrated at the maximum tolerated level. In symptomatic patients, loop diuretics remain the treatment of choice with dosage adaptation according to symptoms and fluid management. Aldosterone antagonists are indicated in patients with severe heart failure (i.e., NYHA class 3 or 4) and creatinine clearance above 30 ml/min. Their combination with RAS blockers warrants strict biological follow up. PMID- 21033493 TI - [Non-medical therapy in heart failure: instrumental treatment and cardiac transplantation]. AB - Circulatory support devices and cardiac transplantation are closely interlinked and are the treatment of severe heart failure refractory to medical therapy. In acute situation, ECMO allows stabilization of unstable hemodynamic situation related to cardiogenic shock. In patients who require longer term support, the use of continuous flow pumps is associated with better survival and better quality of life. Those pumps can be used either as a bridge to transplantation or as a bridge to recovery but also as destination therapy. Early implantation before occurrence of severe right heart failure allows preferential use of LVAD. Approximately 350 cardiac transplantations are performed every year in France. Indication in based on several criteria appreciating the severity of functional impairment. Contra-indications have to be discussed case by case, and chronologic age should not be a too rigid limit. High urgency list allows transplanting the sickest patients in priority. Conditional half-life in patients surviving the first year post transplantation is 12 years. Mechanical circulatory support and cardiac transplantation should be used as complementary treatment of severe heart failure in order to avoid progressive but sometime irreversible deterioration of patients with chronic heart failure. PMID- 21033494 TI - [Impact of comorbidities for the treatment of heart failure]. AB - Heart failure is frequently associated with comorbidities, either because of the etiology of heart failure, either because the prevalence of this disease is high in older age groups, who are affected by various pathologies. Hypertension, diabetes and renal failure are the most frequent comorbidities. They worsen the prognosis of heart failure, so their management should be precise. In all these situations, besides the specific treatment of the disease, the use of inhibitors of the renin angiotensin system is imperative, due to their proven efficacy in heart failure but also because they have beneficial effects on these co morbidities. However, their use must be strictly monitored, clinically and biologically. In patients with chronic obstructive pulmonary disease, beta blockers can be tried and their dose adjusted according to clinical tolerance; they are contraindicated in patients with asthma. Finally, and especially in older patients, the risk of drugs interactions is harmful and should be constantly looking for. PMID- 21033495 TI - [Acute events in heart failure]. AB - Patients with chronic heart failure are fragile patients who may have acute worsening of heart failure. Major acute events are heart failure decompensation, arrhythmia or conduction disturbance. Acute pulmonary edema is an acute complication, easily managed by nitrates. A cause of worsening heart failure must always be searched. Sudden cardiac death is the most severe complication, mainly related to ventricular tachycardia but sometimes related to severe conduction disturbance or asystole. Biological complications are also possible, such as renal failure or hypo- or hyperkalemia. Regular, clinical and biological monitoring is mandatory with, if needed, therapeutic management in order to avoid such acute events. PMID- 21033496 TI - [Etiological diagnosis of leg ulcers]. AB - Etiological diagnosis of leg ulcers must be the first step of treatment, even if we know that veinous disease is often present. We can build a clinical decisional diagram, which helps us to understand and not forget the other causes of chronic wounds and choose some basic examination, like ultrasound and histological findings. This diagnosis helps to choose the right treatment in order to cure even the oldest venous ulcers. Educational programs should be improved to prevent recurrence. PMID- 21033497 TI - [Management of leg ulcers]. AB - This review discusses current therapeutic options for leg ulcers. Compression therapy remains the first-line treatment for venous ulcers, with the use of an external pressure of 30 to 40 mmHg at the ankle (0.8 < ABPI < 1.3). Superficial vein surgery does not improve healing rates of venous ulcers; however it has been shown to reduce ulcer reoccurrence in the context of a competent deep venous system. In cases of severe arterial insufficiency, lower limb revascularization should be considered if possible. Wounds cleansing does not require antiseptics. Wound debridement is an accepted practice but no studies have been performed evaluating its effectiveness on leg ulcers. No systemic treatment has been given any indication in the treatment or prevention of ulcers. Systemic antibiotics should be considered only if the ulcer presents clinically significant infection (spreading erythema, cellulitis, purulent exudates and fever). Choose a type of dressing depending on the phase of healing and on particulars situations (infection, hemorrhagic, malodorous wounds, dermatitis of surrounding skin). In addition to conventional therapeutic options, patient education and lifestyle interventions should not be forgotten. PMID- 21033498 TI - [Dressings for local treatment of leg ulcers]. AB - The beneficial effect of a moist wound environment has been well established for healing rate of acute wounds, pain relief and debridement of chronic wounds. Modern dressings are occlusive or semi occlusive, classified according to their physical composition and to their performances such as absorbent capacity, hydrating ability, adhesive components and debridement capacity. They are used to control the exudates and to maintain the wound in a moist environment. Published systematic reviews of the value of different types of dressings in the management of chronic wounds provide only weak levels of evidence of their clinical efficacy, in terms of healing rate. Nevertheless, the indications of modern dressings were recently determined according to a systematic review of the literature and to a formal consensus process. Despite the lack of appropriate studies, modern dressings remains a part of the standard of care and are widely used according to the experience of the clinicians, in larger indications than what may be recommended by evidence-based medicine. PMID- 21033499 TI - [Heart failure]. PMID- 21033500 TI - [Standardized patients: one more time]. PMID- 21033501 TI - [Limping and gait disorders in the child]. PMID- 21033502 TI - [Acute and chronic chest pain. Acute chest pain: role of scanning in 2010]. PMID- 21033504 TI - [Arteriosclerosis obliterans of the aorta and lower limbs; aneurysms]. PMID- 21033505 TI - [Obesity in the adult]. PMID- 21033503 TI - [Gastroesophageal reflux in infants, children and adults. Hiatal hernia]. PMID- 21033506 TI - [Therapeutic evaluation and the level of proof]. PMID- 21033507 TI - [The Hotel-Dieu of Louhans]. PMID- 21033508 TI - Disease versus dimension in diagnosis. PMID- 21033509 TI - Principles underlying mental health legislation. PMID- 21033510 TI - [The clinical efficacy of Thumper modal 1007 cardiopulmonary resuscitation: a prospective randomized control trial]. PMID- 21033511 TI - Forgotten histories: three stories of black girls from Barnardo's Victorian archive. PMID- 21033512 TI - Dreaming about Irma. PMID- 21033513 TI - Story-telling and history construction: rereading George Cadbury's Bournville model village. PMID- 21033514 TI - Silencing the unmentionable: non-reproductive sex and the creation of a civilized Argentina, 1860-1900. PMID- 21033515 TI - ["Unashamed scholars have touched his nakedness." The discourse over genius, madness, and degeneracy in Belgium ca. 1900]. PMID- 21033516 TI - Power and inheritance: male domination, property, and family in eastern Europe, 1500-1900. PMID- 21033517 TI - Widows' rights questioned: Indians, the state, and fluctuating gender ideas in central highland Ecuador, 1870-1900. PMID- 21033519 TI - Water supply in Welsh towns, 1840-1900: control, conflict and development. PMID- 21033520 TI - The devil and modernity in late nineteenth-century Buenos Aires. PMID- 21033521 TI - Sewing machines: liberation or drudgery for women? PMID- 21033522 TI - New Delhi metallo-beta-lactamase-1 (NDM-1): an emerging threat among Enterobacteriaceae. PMID- 21033524 TI - Pioneers in the Victorian provinces: veterinarians, public health and the urban animal economy. PMID- 21033523 TI - Sexual modernity as subject and object. PMID- 21033525 TI - [Tubular resection of the bronchus]. PMID- 21033526 TI - [A case of localized cystic aneurysm of the ascending aorta complicated with aortic regurgitation (class III to IV) and developing cardiac tamponade]. PMID- 21033527 TI - [Imaging diagnosis: Q & A. Extravasation of a contrast medium into the myocardium of the left ventricular wall]. PMID- 21033528 TI - The Vienna declaration. PMID- 21033529 TI - Demagogues at the helm. PMID- 21033530 TI - A shared vision for public health: then and now. PMID- 21033531 TI - Alcohol consumption: a different kind of Canadian mosaic. AB - OBJECTIVES: To determine the way Canadians consume alcohol beyond drinking amounts and to verify if the drinking act is similar across provinces given that, in Canada, alcohol policies come under provincial jurisdiction. METHODS: Subjects were 10,466 current drinkers (5,743 women and 4,723 men) aged 18 to 76 years, who participated in the GENACIS Canada study. RESULTS: In Canada, there are three main patterns of consuming alcohol. Maritimers tend to drink more per occasion, report more binge drinking and largely prefer beer. In the Prairies, people tend to drink less, to drink less often during a meal and to favour spirits. Finally, drinkers from Quebec, Ontario and British Columbia drink more often, drink wine more often, drink spirits less often, and drink more often during a meal than drinkers from the other provinces. The same patterns are observed in both sexes, although the differences across provinces are less pronounced among women. CONCLUSION: Knowledge about these three drinking groups should be used to increase the legitimacy and effectiveness of alcohol policies in general. PMID- 21033532 TI - Tobacco smoking and colorectal cancer: a population-based case-control study in Newfoundland and Labrador. AB - OBJECTIVE: Newfoundland and Labrador (NL) has the highest incidence rate of both colorectal cancer (CRC) and smoking prevalence in Canada. The objective of this study was to examine if CRC is associated with smoking in this population. METHODS: Newly diagnosed cases identified between 1999 and 2003 were frequency matched by 5-year age group and sex with controls selected from the residents of NL through random digit dialing. A total of 702 cases and 717 controls consented to participate in the study and completed a set of self-administered questionnaires. Measures of tobacco use included type of tobacco, age of initiation of smoking, years of smoking, years since started smoking, number of cigarettes smoked daily, pack years, and years since abstention from smoking. Odds ratios were estimated using multivariate logistic regression. RESULTS: In comparison with non-smokers, former and current smokers were at a significantly elevated risk of CRC with corresponding odds ratios of 1.36 and 1.96. The risk significantly increased with cigarette smoking years, the amount of cigarettes smoked daily, and cigarette pack years. The risk significantly decreased with years of abstention from smoking cigarettes. This association was stronger among drinkers and in men. In addition, this effect was observed to be slightly stronger for rectum than colon cancer. DISCUSSION: In summary, cigarette smoking increased the risk of CRC in the NL population. The risk of CRC associated with cigarette smoking varies by sex, drinking status, and site of CRC. PMID- 21033533 TI - Physician smoking status may influence cessation counseling practices. AB - OBJECTIVE: Smoking cessation counseling practices may differ between physicians who smoke and those who have quit or never smoked. METHOD: Of 917 general practitioners (GP) in Montreal mailed self-report questionnaires in 2000 and 2004, 610 provided data on their smoking status and counseling practices. RESULTS: Seven percent were current smokers, 32% were former smokers, and 61% were never-smokers. Current smokers were more interested than never- or former smokers in learning about counseling methods (64%, 56%, 45%, respectively; p = 0.018). In multivariable analyses, current smokers were less likely than never smokers to ascertain the smoking status of their patients (OR 0.6, 95% CI 0.2 1.6); to provide advice on how to quit (OR 0.6, 0.3-1.3); and to provide complete cessation counseling coverage (OR 0.5, 0.2-1.1). Former smokers were more likely to provide adjunct support (OR 1.5, 1.0-2.4). CONCLUSION: GP smoking status was associated with the content of their cessation interventions with patients who smoke. Taking physician smoking status into consideration in the design of cessation training programs may improve cessation counseling interventions. PMID- 21033534 TI - Patterns of HIV testing among Ontario physicians. AB - OBJECTIVE: HIV testing is important for HIV prevention and control. Nevertheless, approximately 35% of HIV infections in Ontario remain undiagnosed. We examined patterns of HIV testing among physicians to determine provider-related factors associated with HIV testing in Ontario. METHODS: Providers identified from HIV test requisitions submitted to the Ontario Public Health Laboratory in 2006 were linked to a database of Ontario physicians using probabilistic matching. We examined HIV testing frequency by demographic characteristics and physician specialty. In multivariate logistic regression, we assessed factors associated with high testing frequency (20+ tests). RESULTS: 12,477 physicians (59.3% of Ontario physicians) prescribed at least one HIV test in 2006; the proportion was highest in Central East/other (72.4%) and Northern (69.4%) regions compared to others (53.7-58.7%), and highest among the most recent graduates (68.4% versus 59.0% among earlier graduates). A substantial proportion of physicians in family medicine/general practice (83.6%), obstetrics/gynecology (82.1%) and internal medicine (47.7%) prescribed HIV testing. Overall, most physicians (67.5%) prescribed fewer than 20 tests. High testing frequency was significantly associated with practice in Toronto (AOR 2.95), Central East/other (AOR 2.02), or Ottawa region (AOR 2.28), and specialty in family medicine/general practice (AOR 11.47), obstetrics/gynecology (AOR 6.31) or internal medicine (AOR 1.37). Physician sex and graduation country were not associated with high testing in multivariate regression. Of 361,609 tests, 1,048 (0.29%) were HIV-positive; 436 physicians (3.5%) had at least one HIV-positive result. CONCLUSION: HIV testing among Ontario physicians varied substantially by health region, graduation year and specialty. These factors should be considered when delivering continuing medical education on HIV testing. PMID- 21033535 TI - HIV counselling and testing in Nova Scotia: the provincial strategy in the context of an international debate. AB - Nova Scotia, as a small province in Atlantic Canada, provides health care professionals and policy analysts with unique challenges for developing and implementing a strategy for accessible and acceptable HIV counselling and testing. Despite universal health care in Canada, barriers and challenges persist in relation to HIV counselling and testing programs and services in Nova Scotia. It is therefore necessary to examine the unique circumstances in the provision of programs and services in Nova Scotia prior to the possibility of adopting international HIV counselling and testing standards and guidelines being implemented in other jurisdictions. Nova Scotia's provincial strategy on HIV/AIDS promotes a harm-reduction approach for different populations in various service settings, recognizing the diverse circumstances and experiences of people living in Nova Scotia. By contrast, the Centers for Disease Control (CDC) recommended strategy promotes opt-out testing and in some instances alters the requirement of informed consent. As the Public Health Agency of Canada (PHAC) revises the national HIV counselling and testing policies, it is imperative to address the unique characteristics of Nova Scotia's provision of services, and how divergent strategies have the potential to address or compound the barriers to access that exist in this province's communities. PMID- 21033536 TI - Trends in antibiotic utilization in Vancouver associated with a community education program on antibiotic use. AB - OBJECTIVE: "Do Bugs Need Drugs" (DBND) is a community education program that was implemented in British Columbia (BC) in September 2005 to decrease inappropriate antibiotic use. This study conducted descriptive analyses of the association between DBND and changes in overall, pediatric, drug-specific, and indication specific antibiotic utilization rates in Vancouver, BC. METHODS: Utilization data on all oral solid and liquid antibiotics classified as "antibacterials for systemic use" were obtained from BC PharmaNet for the years 1996 to 2008. Utilization data were linked to physician billing data to allow indication specific analyses. Following conversion to the defined daily dose (DDD), the Holt Winters exponential smoothing method was used to project expected antibiotic use in the period after implementation based on use prior to implementation. Differences between expected and observed utilization rates were calculated. RESULTS: Overall antibiotic use has stabilized in recent years (16.2 DDD/1000 population/day in 2008). Fluoroquinolone use remains high (1.5 DDD/1000 population/day), as does the steadily increasing use of newer macrolides (1.1 to 2.7 DDD/1000 population/day between 1996 and 2008). Encouraging declines in overall and indication-specific prescription rates among children were observed. Following 3 years of DBND activities, antibiotic use was 5.8% lower than expected and the number of prescriptions dispensed to children was 10.6% lower than expected. CONCLUSIONS: This ecological study reports improvements in antibiotic use that occurred simultaneously to the delivery of the DBND program in Vancouver. However, we did not find a lowering of all targeted classes. Policy directives limiting the use of certain antibiotics may be required. PMID- 21033537 TI - Skin cancer prevention in Canada. Preface. PMID- 21033538 TI - The UV index: definition, distribution and factors affecting it. AB - The UV Index was introduced in Canada in 1992 in response to growing concerns about the potential increase of ultraviolet (UV) radiation due to ozone depletion. The index was adopted as a standard indicator of UV levels by the World Meteorological Organization and World Health Organization in 1994. This survey article gives an overview of the UV Index and the main features of its geographical distribution. UV index values are determined from measurements made by ground-based spectrometers, broad-band filter radiometers and multi-filter radiometers. Radiative transfer models are used to estimate UV Index values from other types of geophysical observations, primarily column ozone and cloud thickness. UV Index values can also be retrieved from satellite measurements of atmospheric ozone and cloud cover. Forecasts of UV Index values are now widely available and are intended to be used by the public as a guide to avoid excessive exposure to UV radiation. Over the US and Canada, mean noontime UV Index values in summer range from 1.5 in the Arctic to 11.5 over southern Texas and can be as high as 20 at high elevations in Hawaii. The UV Index is also often used to quantify UV levels in studies investigating the impact of UV on other biological and photochemical processes. Factors affecting the UV Index, such as the sun elevation, total amount of ozone in the atmosphere, cloud cover, reflection from snow and local pollution, are also discussed. Since its introduction in 1992, the UV Index has become a widely used parameter to characterize solar UV. Information about it can be useful for helping people avoid excessive levels of UV radiation. PMID- 21033539 TI - The Second National Sun Survey: overview and methods. AB - The Second National Sun Survey (NSS2) was carried out in 2006 to estimate ultraviolet radiation (UVR) exposure, sun protection and related knowledge, attitudes and beliefs among Canadians. This paper provides a detailed overview of NSS2 methods and discusses the strengths and limitations of the survey. The NSS2 consists of two questionnaires administered to two samples of adults (age 16+ years). The base sample provides in-depth information on UVR exposure, protective behaviours, tanning, and knowledge, attitudes and beliefs about sun safety for adults, as well as some sun behaviour information for a sample of their children aged 1-12 years. The shorter comparison sample facilitates direct comparison with the 1996 first national sun survey. Data were collected using computer-assisted telephone interviewing, and sample weights were computed for all respondents for estimation and analysis of both adult and child data. Base sample interviews were completed for 7,121 adults, of whom 1,437 reported on the sun behaviour of one of their children, and the comparison sample yielded 2,115 interviews. Response rates were 63% for both surveys. The NSS2 provides in-depth and up-to-date UVR exposure information among Canadians. The results of this survey will aid health promotion experts and policy-makers in developing effective programs to minimize UVR exposure. A public use data file and training in statistical analysis of the NSS2 has been made available to data analysts from across Canada. Key strengths and limitations identified in this survey will inform the development and implementation of future sun surveys. PMID- 21033540 TI - Sun behaviour in Canadian children: results of the 2006 National Sun Survey. AB - Childhood sun exposure is a particularly important determinant of skin cancer, yet little data are available for children. This paper describes sun behaviour among Canadian children for the summer of 2006. As part of the Second National Sun Survey (NSS2), 1,437 parents reported on the time spent in the sun, and the frequency of sun protection behaviours and sunburning for one of their children aged 1 to 12 years. Analysis was carried out using complex survey procedures in SAS and STATA. The majority of children (94%) spend at least 30 minutes in the sun on a typical summer day; however, regular sun protection is only commonly reported for young children (1 to 5 years) and involves covering their heads and wearing sunscreen (85%). The frequency of other protective behaviours is much lower, and sun protection decreases with age. Older children are also twice as likely to spend extended time in the sun and to get a sunburn. Among older children, boys are more likely to cover their heads and girls are more likely to wear sunscreen. Regular sun protection among Canadian children is low, given their sun exposure. Heavy reliance on sunscreen is consistent with previous reports and indicates that other measures, such as seeking shade and wearing protective clothing, need to be promoted. Riskier sun behaviour among older children may reflect decreased parental control, as well as changing attitudes and peer pressure, and highlights the importance of adult role models and targeted interventions for this age group. PMID- 21033541 TI - Work-time sun behaviours among Canadian outdoor workers: results from the 2006 National Sun Survey. AB - The objective of the study was to describe summer work-related sun behaviours among Canadian outdoor workers. Information on time in the sun and sun protection practices at work during the summer of 2006 were collected from 1,337 outdoor workers aged 16-64 years as part of the Second National Sun Survey. Proportions (and 95% confidence intervals) were estimated using procedures appropriate for complex survey designs. Twenty-six percent of all Canadians, 39% of males and 33% of those aged 16-24 years work outdoors during the summer. Although 41% spend four or more hours daily in the sun at work, just over half always or often protect themselves by covering their heads (58%), wearing protective clothing (56%) or wearing sunglasses (54%), and only 29% use sunscreen. Males and those aged 16-24 spend the most work time in the sun but are the least likely to use protection. The prevalence of outdoor work and sun behaviours varies among regions. Study findings confirm the need for strategies to reduce time in the sun and increase the use of sun protection among outdoor workers. In order to be effective, these strategies must include both enhanced workplace policies and practice, and increased individual use of sun protection. PMID- 21033542 TI - Burden of malignancy after a primary skin cancer: recurrence, multiple skin cancers and second primary cancers. AB - The current paper summarizes relevant recent research on the high risk of recurrence, multiple skin cancers and second primary cancers in the growing number of people with a history of skin cancer; the ultimate purpose is to better assess the burden of malignancy following skin cancer. A number of challenges exist in identifying and tracking both melanoma and non-melanoma skin cancer (NMSC) cases. Most jurisdictions do not routinely track NMSC cases and, even if they do, it is customary to only include the first diagnosis. There are variable rules for counting multiple melanoma cancers, and recurrences are not considered for either major type of skin cancer. Applying insights from recent studies of this issue to Canadian cancer statistics would increase reported diagnoses of NMSC by about 26% and melanoma by 10% in this country. This approach to a fuller assessment of the burden of skin cancers has been called a "diagnosis-based incidence approach" as compared with a "patient-based incidence approach". A further issue that is not usually taken into account when assessing the burden of skin cancers is the 20% to 30% elevated risk of noncutaneous second primary cancers following a primary skin tumour. In summary, individuals with skin cancer are subject to a high risk of recurrence, multiple skin cancers and second primary cancers. This burden should be a special concern in the large and growing pool of individuals with a history of skin cancer, as well as among prevention planners. PMID- 21033543 TI - The skin cancer prevention framework: a comprehensive tool for population-level efforts in skin cancer. AB - The Skin Cancer Prevention Team (SCPT) required a comprehensive approach for guiding its efforts in population-level skin cancer prevention. After identifying and reviewing several models, it concluded that an appropriate population-level model applicable to the Alberta context did not exist. Thus, the SCPT, under the Alberta Health Services - Cancer Prevention Program, developed and evaluated a model for Alberta. Three inclusion criteria for a comprehensive framework were identified: 1) use an ecological approach to population health; 2) function as a dynamic tool for planning, implementing and evaluating population-level efforts; and 3) address weaknesses in existing theory in population health and health promotion. Theoretical constructs were layered together, on the basis of the criteria, to develop an omnibus framework. The resulting Framework represents a layering of several constructs used in popular health promotion and population health theories. It merges principles of the realist approach to scientific enquiry with principles of ecological theory. The Framework outlines a three step, dynamic process for planning, implementing and evaluating population-level efforts. It also provides insight into the larger, unifying influences for changes in health outcomes and the complex mechanisms of behaviour change processes at the population level. PMID- 21033544 TI - Nurse practitioner role implementation in Ontario public health units. AB - OBJECTIVES: To identify the barriers and facilitators associated with the implementation of the nurse practitioner (NP) role in Ontario's public health units (PHUs), the NPs' job satisfaction, and the relationship between NP job satisfaction and practice dimensions. METHODS: This descriptive study involved a postal survey of all NPs (N = 29) working in Ontario PHUs. RESULTS: Twenty-eight (96.5%) NPs completed the survey. The facilitators to role implementation most often identified by the NPs were management support, the NPs' knowledge of the PHU programs, and access to PHU programs for their clients. The barriers most often cited were being the only NP working in the PHU, inadequate salary, and lack of coverage when the NP was away. When working with community physicians, the most common facilitators were the trust shown by physicians when making shared decisions and physician respect for the NP. The most common barriers were the unwillingness of specialist physicians to accept referrals from the NP and physicians' lack of understanding of the role. Overall, the NPs were satisfied with working in the PHU, satisfied with their collaborative relationship with physicians and minimally satisfied with their salaries. CONCLUSION: NPs have recently been introduced in PHUs in Ontario. A number of factors have facilitated role integration. At the same time, a number of barriers to their role implementation have been identified and if addressed, can contribute to the optimal utilization of this role in PHUs. PMID- 21033545 TI - Incorporating public health more closely into local governance of health care delivery: lessons from the Quebec experience. AB - BACKGROUND AND OBJECTIVE: In 2004, the Quebec government undertook a major reorganization of its health care system by integrating public health more formally into local governance structures. In all, 95 new organizations - Health and Social Services Centres (CSSS)--were created and given a population-based responsibility. This mandate required that CSSSs broaden their range of services by adopting a population-based plan and integrating public health into their activities. To accomplish this, they needed to link public health and health care issues more formally within a single governance structure. The aim of this article is to identify and analyze various activities undertaken by CSSS managers to fulfill their population-based responsibility. METHODS: We conducted a longitudinal case study of two CSSSs (2005-2008). Our analyses are based on real time observations of 144 meetings of decision-makers/managers and professionals at the regional and local levels, 46 interviews with managers, as well as secondary data. RESULTS: CSSSs focused on five areas of population-based responsibility: primary health care, specialized services, vulnerable groups, health promotion and social services. Over time, the activities developed by CSSSs in relation to these five areas reflected an increasingly population-based perspective on the delivery of health care services. CONCLUSION: Service planning in the two cases under study is now based on a broader view of the health care continuum, and managers invest more time and resources in preventive interventions. Our study provides key information on the process of integrating a population-based perspective and preventive approaches in the planning and delivery of primary care services. PMID- 21033546 TI - Vitamin D intake from food and supplements among Ontario women based on the US block food frequency questionnaire with and without modification for Canadian food values. AB - OBJECTIVES: To measure and compare dietary vitamin D intake among women in Ontario using a modified Block 1998 (US) food frequency questionnaire (FFQ) before and after modification for Canadian-specific vitamin D food fortification. METHODS: An age-stratified random sample of 3,471 women in Ontario (aged 25-74) was identified using random digit dialing methods. Standard US food values and a modified Canadian-specific vitamin D nutrient analysis were applied to the FFQ. RESULTS: Intake of vitamin D from foods (Canadian nutrient analysis) was 5.3 +/- 3.4 microg/day (mean +/- SD) and 45% of women reported vitamin D intake from supplements. Total vitamin D intakes met the current Adequate Intakes of 5, 10 and 15 microg/day for only 62%, 47%, and 28% of women aged < or = 50, 51-70 and > or = 71, respectively. Relatively high agreement was found between the US and Canadian nutrient analysis methods of measuring vitamin D from food (weighted kappa = 0.74, 95% CI 0.72-0.76). Intake differences (US minus Canadian) ranged from -5.0 microg/day to +2.0 microg/day (1st-99th percentile); however, the mean difference was only -0.54 microg/day (95% CI: -0.58 to -0.50). CONCLUSIONS: Lower than recommended total vitamin D intakes were observed among our study participants which may negatively impact the health status of women. Adjustment for Canadian food fortification and the inclusion of fatty fish had little impact on the measurement of vitamin D from food. PMID- 21033547 TI - Health status of refugees settled in Alberta: changes since arrival. AB - OBJECTIVE: This paper sought to examine which pre- and post-migration factors might be associated with changes in refugees' health status. METHODS: Using linear regression, the associations between pre- and post-migration factors and changes in self-rated mental and physical health status were examined in 525 refugees from the 1998 Settlement Experiences of Refugees in Alberta study. RESULTS: Having spent time in a refugee camp and having held professional/managerial jobs in one's home country were associated with a greater decline in mental health status since arrival in Canada. Having completed a university degree in one's home country was associated with a greater decline in physical health status. Being employed was associated with greater improvements in mental health status. Perceived economic hardship was associated with greater declines in physical health status. A higher number of settlement services received during the first year in Canada was associated with greater improvements in both mental and physical health status. Longer residence in Canada was associated with greater declines in physical health status but not in mental health status. CONCLUSION: While little can be done to alter refugees' pre migration experiences, public policies can affect many post-migration experiences in order to mitigate the negative health consequences associated with resettlement. Results of this study point to the need for continued provision of settlement services to assist refugees with job training, labour market access, and credential recognition, as well as counseling for refugees who experienced the trauma of living in a refugee camp. PMID- 21033548 TI - A meta-synthesis of post-migration changes in marital relationships in Canada. AB - OBJECTIVES: Immigration to a new country constitutes a major life change and challenge that can directly and indirectly affect the health of individuals and families. A systematic review was conducted to identify post-migration changes and understand their impact on immigrants' marital relationships in Canada. METHOD: Using Noblit and Hare's meta-ethnography steps and Paterson et al.'s meta data method, we conducted a meta-synthesis of qualitative articles. SYNTHESIS: Four journal articles and one book chapter met the inclusion criteria. Our synthesis of these studies identified three key themes reflecting the major post migration changes experienced by couples: changes in gender and sexual relations, loss of social networks and support, and de-skilling and de-professionalization. The importance of communication emerged as a fourth theme that cut across the three key themes. These post-migration changes were common across nine ethnic communities, and affected the couple as a unit as well as individuals within this unit, both negatively and positively. The changes were associated with four outcomes: abuse, separation/divorce, staying with each other, and resilience. The synthesis also showed various pathways that link the post-migration changes and their outcomes. CONCLUSION: Understanding post-migration changes, their outcomes, and the pathways that link them is useful in developing health promotion activities to promote couples' resilience as well as health interventions to reduce the negative impact of the changes on couples and individuals. These activities and interventions must be planned at micro, meso, and macro levels of society. PMID- 21033549 TI - The impact of international travel on the epidemiology of enteric infections, British Columbia, 2008. AB - OBJECTIVE: Travel-related enteric infections likely represent a large proportion of all enteric infections in British Columbia (BC). The objective of this study was to assess the proportion of enteric infections in BC reported in 2008 associated with international travel in order to understand trends in infections so that targeted interventions can be implemented. METHODS: Travel information for all reported cases of salmonellosis, verotoxigenic E. coli (VTEC) infection, shigellosis, Vibrio parahemolyticus infection, botulism, cholera, listeriosis, typhoid fever, paratyphoid fever, hepatitis A infection, cryptosporidiosis, cyclosporiasis and a representative proportion of campylobacteriosis was collected. Temporal, demographic and geographic analysis was conducted comparing locally-acquired infections to infections acquired during international travel. Travel destination was compared between cases of enteric infections and the BC population. RESULTS: Of the 3,120 enteric infections reported in 2008, 60% were classified as locally-acquired and 40% were associated with international travel. The proportion of infections associated with international travel was highest among 30 to 39 year olds. Locally-acquired infections were highest in the summer months and international travel-related infections were highest in the winter. Asia and Mexico were the most common destinations in relation to enteric infections acquired internationally. The proportion of enteric infections was significantly higher than the proportion of the BC population travelling to these areas. CONCLUSIONS: The proportion of enteric infections in BC associated with international travel is significant. Identification and assessment of locally acquired infections separately from those associated with international travel will improve assessment of trends and rates for enteric infections in BC and lead to more targeted public health actions. PMID- 21033550 TI - Hospitalization for trichinellosis and echinococcosis in Canada, 2001-2005: the tip of the iceberg? AB - OBJECTIVES: This study was undertaken to measure the incidence of echinococcosis and trichinellosis hospitalization in Canada, and to compare these incidence rates between residents of northern regions and the rest of the Canadian population. METHODS: Cases hospitalized in 2001-2005 for either echinococcosis or trichinellosis were retrieved from the hospital morbidity database (HMDB) held by the Canadian Institute for Health Information. Crude and standardized incidence rates were calculated by province and by latitude range. RESULTS: A total of 108 echinococcosis and 14 trichinellosis hospitalizations were found, yielding incidence rates of 0.72 and 0.09 per million per year, respectively. There was a clear south-north gradient in the incidence of echinococcosis hospitalization, the highest incidence (2.9 per million per year) being found north of the 55th parallel. The risk of echinococcosis hospitalization was also significantly higher in women than in men (RR 1.92, 95% CI 1.29-2.87). For trichinellosis, the highest incidence (42 per million per year) was found in Nunavut and Northern Quebec. CONCLUSION: Incidence of hospitalization for echinococcosis and trichinellosis is low at the national level. However, significantly higher rates have been measured in northern regions of Canada despite the fact that both diseases are theoretically preventable and that a Trichinella control program is in place in Nunavik. Further efforts, probably educational in nature, will be required to reduce the incidence of these infections in high-risk areas. PMID- 21033551 TI - Incidence of clubfoot in Uganda. AB - BACKGROUND: While the congenital clubfoot deformity is a common deformity recorded in Uganda, the incidence of the condition had never been accurately determined. The objective of this study was to measure the overall incidence of congenital clubfoot deformity in a representative sample of births. METHODS: A study of all babies born with foot anomalies took place from March 2006 to October 2007. The study was based at 8 Regional Hospitals with active maternity units and a functioning clubfoot clinic. All babies with foot deformities at birth at any of eight centres as detected by the delivery room staff were referred to the respective centre's clubfoot clinic. The children were examined by clubfoot clinic orthopedic officers who diagnosed the specific deformity. Children referred to the clinic from any source and born at the maternity unit were included in the study. The denominator was all live births at the centre during the study period. RESULTS: The total number of live births during the study period was 110,336. The maternity units of the centres identified 290 infants with a foot deformity. One hundred and thirty infants born during the study period were diagnosed in the clubfoot clinic as having a congenital clubfoot deformity. The proportion of infants with a clubfoot deformity was 1.2 per 1000 births over the 20-month period. The male to female ratio was 2.4:1. RECOMMENDATION: The rate of clubfoot deformities in the newborn can be used to estimate the numbers of children who should be treated and to estimate resource needs for the identification and management of this treatable congenital malformation. By comparing the number of those treated with the expected number of cases, the numbers of children with neglected clubfoot can be calculated. PMID- 21033552 TI - Self-reported anthropometric data. PMID- 21033553 TI - The suitability of selected methods of nucleic acid extraction for detecting Rhodococcus equi DNA in tracheobronchial wash fluid using PCR. AB - The aim of the present study was to compare the effectiveness of selected DNA extraction methods for the detection of Rhodococcus equi from tracheobronchial wash fluid by PCR. Three methods of nucleic acid extraction were evaluated, based mainly on the activity of proteolytic enzymes. A commercial kit for isolation and purification of bacterial DNA was also used in the study. In one procedure, an additional component, the cationic detergent CTAB, was used. It has been found that the traditional enzyme digestion methods used with the tracheobronchial wash fluid are more suitable to prepare DNA matrix for PCR comparing with commercial DNA isolation kit. Minimum numbers of bacteria detected with the use of traditional enzyme digestion methods and commercial kit were 100 and 500 cells, respectively. Based on the results of the study we can recommend the enzymatic digestion method along with CTAB as an additional component. PMID- 21033554 TI - Prion protein gene polymorphism and blood lymphocyte profile in cows naturally infected with bovine leukemia virus. AB - The polymorphic loci of the bovine prion protein (PRNP) gene, comprising 23-bp insertion/deletion (23-bp indel) within the promoter sequence and 12-bp insertion/deletion (12-bp indel) within the intron 1 sequence, are located in regions which play a key role in gene expression. The objective of this study was to determine whether the 23-bp and 12-bp insertion/deletion polymorphism within the PRNP gene leads to significant differences in the blood lymphocyte profile and to investigate changes in the composition of these cells in cattle naturally infected with Bovine Leukemia Virus. An analysis of the effect of the bovine PRNP gene polymorphism on the blood lymphocyte profile revealed considerable differences between animals with the 23-bp indel genotypes, and small and statistically non-significant differences between those with the 12-bp indel genotypes. 23-bp del/del homozygotes had a significantly lower percentage of T lymphocytes with the phenotypes CD2 (P < 0.01), CD8 (P < 0.01) and WC1-N2 (P < 0.05), and a higher ratio of CD4 to CD8 T lymphocytes, compared to animals with the 23-bp ins/ins genotype. The obtained results indicate that the 23-bp indel polymorphism, in contrast to the 12-bp indel polymorphism, has a significant effect on changes in the blood lymphocyte profile. The size of blood lymphocyte subpopulations was also found to change under the influence of enzootic bovine leukosis. The direction of those changes in EBL-positive animals is consistent with that observed in 23-bp del/del homozygotes, which may testify to the adverse effect of this genotype on immunological efficiency. PMID- 21033555 TI - The effect of multigenerational diet containing genetically modified triticale on immune system in mice. AB - The safety assessment of genetically modified (GM) food and feed is performed to identify the possible effects upon animal and human health, also the long-term, multigenerational influence upon functioning of different organs and systems, such as the immune system. In this study C57BL/6J mice were fed for five consecutive generations with pellets containing 20% of conventional triticale grain (control) vs. pellets containing 20% of the transgenic triticale grain resistant to BASTA herbicide (experimental). The F5 experimental animals showed enlarged inguinal and axillary lymph nodes, but not spleens, and increased WBC counts in blood (but within the norm for Mus musculus). Immunophenotyped cell suspensions derived from spleens, inguinal and axillaris lymph nodes and PBMCs from blood showed the significant decrease in the percentage of T cells in spleen and lymph nodes and the B cells in lymph nodes and blood of the F5 experimental mice in comparison to the control F5 mice. Immunoblotting analysis of IL-2, IL-4, IL-10, IL-12, IL- 6, IFN-gamma levels in serum showed significantly increased IL 2 levels and decreased IL-6 levels in the F5-experimental mice sera. No significant changes in the levels of IgE in sera in both mice groups were observed. The obtained results indicate that multigenerational use of feeds for rodents containing the GM-triticale leads to expansion of the B cell compartment in the secondary lymphoid organs, but it is not caused by malignant processes or the allergic response. PMID- 21033556 TI - Efficacy of different levels of Escherichia coli phytase in broiler diets with a reduced P content. AB - Escherichia coli-derived 6-phytase expressed in Pichia pastoris (Optiphos) was added to broiler rations with considerably reduced levels of phosphorus (by 1.5 g/kg). This experiment, performed over a five-week period, involved Ross 308 male chickens kept in battery cages. Each group was divided into 9 subgroups, each of 9 chickens (81 birds per treatment). Birds were allocated to a positive control group (I), a negative control group (II) and three phytase-supplemented groups (III-V--the diet as in group II + 250, 500 and 750 FTU Escherichia coli phytase/kg feed, respectively). The major components of starter and grower diets were corn, soybean and wheat meals. Starter and grower diets (in meal form) contained 6.73 and 6.05 g total P/kg, 4.05 and 3.46 g available P (aP)/kg, respectively, in group I, and 5.23 and 4.55 total P/kg, 2.54 g and 1.95 g aP /kg, respectively, in groups II-V. Phytase efficacy was evaluated based on performance results, carcass quality and bone mineralization. P reduction in group II decreased weight gains by 9.1% and increased feed conversion by approximately 8.4%, compared with group I. Diet supplementation with phytase in groups IV and V significantly compensated for the decrease in performance observed in group II. The differences in dressing percentage between group II and groups III and V were significant. Phosphorus reduction in the diets negatively influenced the process of bone mineralization, which was enhanced by phytase supplementation. PMID- 21033557 TI - Epidemiological features of Morel's disease in goats. AB - Morel's disease caused by Staphylococcus aureus subsp. anaerobius was diagnosed for the first time in Poland in October 2006 in a goat flock. A second infected flock was found two months later. The course of the disease in both flocks was observed for 15-17 months. Clinical manifestation was confined to abscesses located near major superficial lymph nodes, mostly: superficial cervical, subiliac, parotid and mandibular. At necropsy no other lesions were found. The incubation period was estimated at 3 weeks. Clinical signs were seen both in young and adult goats and up to 7 abscesses in one animal were noted. Abscesses tended to persist for 1 to 5 months, then rupture and heal completely. The initial high in-flock point prevalence in both flocks (93.6% and 84.4%) dropped to approximately 10-30% during next 3-4 months. Until the end of the observation period the in-flock point prevalence remained at this level and only single abscesses were observed, mainly in young animals. No influence of the concurrent caprine arthritis encephalitis virus (CAEV) infection on the clinical course of Morel's disease was noticed. It is to be concluded that the clinical course of Morel's disease in a goat flock resembles caseous lymphadenitis (CLA). However, in Morel's disease abscesses occur more frequently in young goats and are located near, not inside, the lymph nodes, as in the case with CLA. Also, the incubation period of Morel's disease seems to be shorter (3 weeks versus 2-6 months in CLA). PMID- 21033558 TI - Indices of non-specific and specific humoral immunity in pigs immunomodulated with the Bioimmuno preparation and/or immunised with the Respisure One vaccine against mycoplasmal pneumonia of swine. AB - The purpose of the study was to determine the influence of the Bioimmuno preparation administered in feed and/or immunisation with the Respisure One vaccine on the development of selected indices of non-specific and specific humoral immune response against Mycoplasma hyopneumoniae (Mhp) infections in pigs. The study was performed on 28 piglets at the age of 4 weeks, divided into four equal groups. The biopreparations were administered according to the following pattern: group I--Bioimmuno (IFI Olsztyn, Poland) with feedstuff at amount of 1 kg/50 kg of feed for 48 h before vaccination with Respisure One (Pfizer) on day 28 of life; group II--Bioimmuno only (1 kg/50 kg feedstuff) for 48 h before vaccination with Respisure One of groups I and III; group III- Respisure One only on day 28 of life (2 ml/animal i.m.) and group C (control)- PBS (2 ml/animal i.m.) simultaneously with vaccination of groups I and III. On days 0, 3, 7, 14 and 21 after immunomodulation and/or immunisation, the serum level of gamma-globulins, the activity of lysozyme (LSM) as well as the serum levels of cytokines: interferon gamma (IFNgamma), interleukin 1 beta (IL-1beta) and interleukin 6 (IL-6) were determined, as indices of non-specific immune response against Mhp infections in pigs. The study has revealed that in piglets after weaning the application of the Bioimmuno and/or Respisure One biopreparations improves the non-specific immunity parameters stimulating an increase in serum levels of gamma-globulins, lysozyme and cytokines (IFNgamma, IL 1beta, IL-6), while late appearing seroconversion confirms a minor role of specific humoral immunity in the protection against Mhp infection. PMID- 21033559 TI - Application of recombinant antigens in serodiagnosis of swine toxoplasmosis and prevalence of Toxoplasma gondii infection among pigs in Poland. AB - In this study, to determine the prevalence of swine toxoplasmosis, 1754 pigs from different regions of Poland were tested for IgG antibodies by an in-house ELISA technique based on native Toxoplasma lysate antigen. Seropositive individuals were found in 19.2% of the examined population. The diagnostic usefulness of three T. gondii recombinant antigens (rMAG1, rSAG1, and rGRA7), either individually or in cocktails (M1: rMAG1 + rSAG1; M2: rMAG1 + rGRA7; M3: rSAG1 + rGRA7; M4: rMAG1 + rSAG1 + rGRA7) were also assessed with serum samples from naturally infected pigs by ELISA analysis. Both rSAG1 and rGRA7 antigens detected specific IgG antibodies with a similar sensitivity (85.3% and 81.3%, respectively), whereas the lower sensitivity was obtained for rMAG1 (only 64%). Better results of reactivity were obtained for mixtures of two antigens: M1 (86.7%), M2 (89.3%) and M3 (92%). Furthermore, the reactivity of three antigens cocktail M4 (97.3%) was much higher than that of individual proteins and combinations containing two antigens. These results suggest that the combination of three recombinant antigens might be useful for the serological detection of T. gondii infection in pigs. PMID- 21033560 TI - Spirocerca lupi isolated from gastric lesions in foxes (Vulpes vulpes) in Sicily (Italy). AB - Spirocerca lupi (Rudolphi 1809) is a cosmopolitan nematode of dogs and wild carnivores. In the past it has been reported in Italy, mainly in southern regions and in Sicily, where the parasite was observed in foxes in 2005. The parasite typically produces nodular masses in the oesophagus and thoracic aorta. During the 2003-2004 hunting season, the authors investigated a total of 55 foxes (Vulpes vulpes) hunted or killed by car accidents in the provinces of Palermo and Agrigento. All the foxes were subjected to necropsy and 6 (9.16%) had S. lupi nodules located exclusively in the gastric wall. The nature of the nodules was determined by opening them and detecting the nematodes inside, which were identified as S. lupi. Some of the nodules were characterized anatomopathologically and histopathologically. The formation of the parasitic nodule in the stomach only suggests a deviation from the route commonly followed by the nematode to reach the oesophagus, the elective anatomical site for completion of its lifecycle. This survey gives a contribution to the epidemiology of this parasite which is severely outdated in Italy and highlights some distinctive features of the life cycle and parasite migration. PMID- 21033561 TI - Clinical, hormonal and ultrasonograph approaches to diagnosing cryptorchidism in horses. AB - Cryptorchidism is a partial or total failure of testicular descent. For a proper diagnosis different methods are required. The main aim of this study was to compare different diagnostic methods. Sixty two horses (15 stallions, 32 cryptorchids and 15 geldings) were used in the experiment. They were clinically examined and ultrasonography was used to locate the testes. Blood samples were taken from the animals to measure the plasma level of testosterone and total estrogen (RIA method). In 22 horses suspected of cryptorchidism, the hCG stimulation test was performed. Blood samples were taken every 20 minutes for 8 hours and then 24 and 48 hours after injection. Clinical examination had a 60% success rate in detecting superficial and profound canal cryptorchids. Inguinal ultrasonography had a 100% rate of detection when the retained testes were in the area of the internal or external inguinal ring. The rate of detection with abdominal cryptorchids was 72.7%. The highest levels of testosterone were found in stallions' blood (2.3 ng/ml), they were lower in cryptorchids (0.68 ng/ml) and lowest in geldings (0.15 ng/ml). Total estrogen levels revealed a similar tendency (respectively: 395 pg/ml, 228 pg/ml and 26 pg/ml). Administration of hCG usually increased the level of testosterone from 0.68 ng/ml to 1.05 ng/ml 60 minutes after injection. We found that to successfully diagnose cryptorchids in veterinary practice a combination of clinical, ultrasonographic and hormonal examinations should be used. PMID- 21033562 TI - Effect of age, hyperplasia and atrophy on collagen parameters in dog prostates. AB - The aim of this study was to examine the quantitative parameters of interstitial collagen in the normal and abnormal (hyperplasia, atrophy) prostates of dogs from 6 months to 11 years of age and older. Prostate specimens were fixed in formalin and processed for light microscopy with HE and Sirius Red. A histomorphometric study of collagen was performed using a computer-assisted image analysis system (Quantimet 520). In each section, under the capsule of prostate, except inflammatory tissue, the percentage volume of collagen, the perimeter of collagen area, and the number of fibers in the field of view were determined. The number of collagen fibers in the field of view and the perimeter of interstitial collagen in mature dog prostates decreased with age (p < 0.01). It was determined that the percentage volume moderately correlated with the amount of collagen fibers in the field of view (R = 0.34, p < 0.01) and markedly correlated with the collagen perimeter (R = 0.74, p < 0.01). The percentage volume of collagen in sexually immature dog prostates (up to 7-8 months of age) and in atrophic prostates was 36% and 44%, respectively. In case of hyperplasia, the percentage volume of collagen did not increase. PMID- 21033563 TI - Antifungal susceptibility of yeasts isolated from secrection of inflamed mammary glands in cows. AB - Antifungal susceptibility of 150 strains of yeasts isolated from the infected mammary secretion of cows was determined. Their susceptibility to amphoterycin B, nystatin, flucytosine, tioconazole, ketoconazole, miconazole, fluconazole and clotrimazole was evaluated using the disc diffusion method on Yeast Nitrogen Base (YNB) and filter paper discs. The most active antifungal agents in vitro were found to be: tioconazole--96.7%, nystatin--95.4%, amphoterycin--94.0%, and flucytosine--92.7% of susceptible strains; the least active were fluconazole and clotrimazole--39.3% and 60.0% of susceptible strains, respectively. The individual species of yeasts were characterized by varied susceptibility to individual therapeutics. PMID- 21033564 TI - Phylogenetic evolution of swine-origin human influenza virus: a pandemic H1N1 2009. AB - The knowledge of the genome constellation in pandemic influenza A virus H1N1 2009 from different countries and different hosts is valuable for monitoring and understanding of the evolution and migration of these strains. The complete genome sequences of selected worldwide distributed influenza A viruses are publicly available and there have been few longitudinal genome studies of human, avian and swine influenza A viruses. All possible to download SIV sequences of influenza A viruses available at GISAID Platform (Global Initiative on Sharing Avian Influenza Data) were analyzed firstly through the web servers of the Influenza Virus Resource in NCBI. Phylogenetic study of circulating human pandemic H1N1 virus indicated that the new variant possesses a distinctive evolutionary trait. There is no one way the pandemic H1N1 have acquired new genes from other distinguishable viruses circulating recently in local human, pig or domestic poultry populations from various geographic regions. The extensive genetic diversity among whole segments present in pandemic H1N1 genome suggests that multiple introduction of virus have taken place during the period 1999-2009. The initial interspecies transmission could have occurred in the long-range past and after it the reassortants steps lead to three lineages: classical SIV prevalent in the North America, avian-like SIV in Europe and avian-like related SIV in Asia. This analysis contributes to the evidence that pigs are not the only hosts playing the role of "mixing vessel", as it was suggested for many years. PMID- 21033565 TI - Effect of different workload and hydrocortisone in vitro on platelet aggregation in athletic horse. AB - The objective of the present study was to evaluate the platelet response to different workload in athletic horse and the influence of hydrocortisone on this response. For this purpose, six Sella Italiana gelding athletic horses, ranging in age from 8 to 10 years and clinically healthy, were subjected to four different exercises: horse-walker, treadmill, obstacle course of 1.00 m and obstacle course of 1.25 m. From all the horses, citrated plasma samples were collected at rest, immediately after exercise and 30 min after the end of the exercise to assess the maximum degree of platelet aggregation and the initial velocity of aggregation (slope) after platelet activation with 10 microM ADP and 20 microM ADP. Successively, the effect of 20 minutes pre-incubation with hydrocortisone in ADP-induced aggregation was determined. One-way repeated measures analysis of variance (ANOVA) was applied to determine significant differences due to experimental conditions (P < 0.05) and, for each sampling time, one-way analysis of variance was applied to determine significant differences due to workload (P < 0.05). Bonferroni's test was applied for post hoc comparison. Our results revealed a statistically significant effect of experimental conditions only after obstacle course of 1.00 m and 1.25 m. These findings showed an inhibition of platelet aggregation during different workload in athletic horses that probably represents a protective endothelial mechanism through the production of nitrix oxide, and a kinetic measurement of the reaction that changes in relation to percentage of aggregation. The mechanism of hydrocortisone had no effect on platelet receptor expression in vitro in athletic horses, so it might be useful to evaluate the effect of different anti inflammatory steroids in order to confirm, or note any differences, with drugs that have the same mechanism of action. PMID- 21033566 TI - Occurrence of gram-negative bacteria in hens' eggs depending on their source and storage conditions. AB - The aim of this study was to analyse the qualitative composition of Gram-negative microbes, mainly of the family Enterobacteriaceae, including pathogenic bacteria such as Salmonella, in the albumens and yolks and on the shells of hens' eggs, depending on their source and on the temperature and duration of their storage. A total of 375 table eggs were studied, from a large-scale poultry farm, a small scale poultry farm and a supermarket. Each group was divided into 5 subgroups according to the temperature and duration of their storage during the study. Two serotypes of bacteria of the genus Salmonella were identified: S. Enteritidis and S. Arizonae. Strains of Salmonella spp. were also isolated. Apart from Salmonella and Escherichia coli, among the most frequently isolated bacteria of the family Enterobacteriaceae were Enterobacter spp., Klebsiella spp. and Citrobacter freundii. Qualitative analysis of the bacterial microflora of the eggs also showed the presence of other Gram negative bacteria, including Acinetobacter spp., Pseudomonas spp., Tatumella ptyseos, Providencia stuartii, Serratia liquefaciens, Flavimonas oryzihabitans, Vibrio metschnikovii, Leclercia adecarboxylata, Kluyvera spp., Rahnella aquatilis, Proteus mirabilis, and Achromobacter spp. The study demonstrated that the conditions applied, i.e., the temperature and duration of storage, did not significantly influence the prevalence of particular species of Gram-negative bacteria in the eggs. However, based on the analysis of contamination of eggs with Salmonella depending on their source, it can be concluded that the system in which the hens are housed affects the risk of contamination of eggs with these pathogens. PMID- 21033567 TI - The effect of heterotypic infections of older horses with equine influenza virus type-2 on some clinical and immunological parameters. AB - Twelve horses, all of them 10 years old, were vaccinated intramuscularly on 0 and 28 days of the experiment with inactivated vaccine containing only antigens of A equi-2/Miami/63. Another three unvaccinated horses, each at the age of 10 years, were the negative control group. One, ten-year-old horse was vaccinated with commercial inactivated vaccine containing both antigens of A-equi-2/Miami/63 as well as A-equi-1/Praha/56 as positive control. Three horses were challenged intranasally with homotypic strain of Miami/63, while six other were challenged with heterotypic strains--three with Suffolk/89 and three with Kentucky/86. Three horses vaccinated with vaccine containing only strain A-equi-2/Miami/63 were not challenged. In the group of three unvaccinated horses, each one was challenged intranasally with different strains studied in this experiment. The horse vaccinated with commercial vaccine was not challenged. Replication of each strain was done in chick embryos. During the experiment blood from horses was collected for hematological and immunological examinations (antigen-specific and antigen nonspecific lymphocyte transformation tests, lymphocyte immunophenotyping, antigen-specific leukocyte migration inhibition test and hemagglutination inhibition test). The statistical analysis showed that the dynamics of lymphocyte immunological reactivity in horses vaccinated with inactivated vaccine containing antigens of A-equi-2/Miami/63 in response to further antigen stimulation (in vitro) was different comparing the homotypic or nearly homotypic challenging with Miami/63 and Suffolk/89 respectively, to the more heterotypic one with the strain Kentucky/86. In horses challenged with classical homotypic strain of Miami/63 no clinical signs were observed. These results confirm that the vaccine shall consist of the strains currently circulating in the horse population. PMID- 21033569 TI - The clinical evaluation of fillings made witch Ketac-Cem after endodontic treatment in dogs. AB - The aim of this study was the clinical evaluation of glass-ionomer material Ketac Cem used after the root canal therapy as filling. The investigations were carried out in 18 dogs. The filling was evaluated according to Rydge's modified scale. The evaluations were done shortly after treatment and repeated after two years. The investigated material is frequently used in veterinary stomatology. Only 22.22% of fillings were qualified to replacement at the second evaluation. PMID- 21033568 TI - Efficacy of mannanoligosaccharides additive to sows diets on colostrum, blood immunoglobulin content and production parameters of piglets. AB - The present results suggest that mannanoligosaccharides (MOS) included in a sow nutrition may affect its immune system and humoral antibody production in colostrum and milk, and thus increase the piglet immunity at the postnatal period. The studies involved sows of the Polish Landrace breed mated with boars (Hampshire x Duroc). In each experiment, the sows were assigned to two groups: control and experimental (MOS). Each group consisted of 16 sows managed in pens (2 animals in each) during pregnancy, whereas at farrowing and lactation period they were placed in individual pens. The basal diet during pregnancy (PR-S) and lactation (LC-S) period contained wheat (40% in experiment I--groups 1 and 2) or triticale (40% in experiment II--groups 3 and 4), as well as barley, soybean meal, soybean oil and mineral-vitamin premix. Throughout both experiments, the sows from the experimental group had a dietary supplement of mannanoligosaccharides (MOS) preparation for 4 of weeks prepartum and 4 weeks of post partum period. A level of the MOS supplementation (8 g of MOS per sow daily) based on the recommendations of the manufacturer. Blood samples were collected from the sows on days 84 (the start of trial) and 110 of pregnancy, after farrowing, and on day 21 of lactation period, while from the piglets at birth and on day 21 of age. Colostrum was collected between 1-3, 12, 24 and 48 h after farrowing. The blood samples taken from sows and piglets as well as the samples of sow colostrum and milk were evaluated for the presence of IgG, IgA and IgM antibodies. The present study has provided considerable evidence that MOS supplementation of sows feedstuff before and after farrowing (4 weeks before and 4 weeks after) exerts a positive effect on IgG content in the colostrum and plasma of sows and following this on serum IgG level in the suckling piglets. Higher level of colostral (passive) immunity influences positively body weight gain and survival rate of the piglets at weaning. PMID- 21033571 TI - Several cases of dirofilariosis accidentally diagnosed in dogs from Poland, including two PCR positive Dirofilaria repens cases. AB - The aim of the present study was a description of several microfilaremia cases diagnosed in dogs from Poland. The study was conducted on cytological samples of pathologic masses and peripheral blood smears taken for diagnostic purposes from dogs showing a various clinical findings. The presence of the parasites in tissue samples was observed in 8 dogs, additionally, in 2 of these dogs PCR analysis of blood samples revealed the presence of D. repens DNA. PMID- 21033570 TI - Analysis of the chemical coding of neurons in the intermediate thoracic ganglion of the pig. AB - The pig has been widely used as a model in cardiovascular research. A unique feature of the porcine extrinsic sympathetic cardiac nerves is that they arise from intermediate ganglia in the thoracic cavity. The localization and pattern of distribution of nerve cell bodies and fibers containing tyrosine hydroxylase (TH), dopamine B-hydroxylase (DBH), neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), somatostatin (SOM), galanin (GAL), methionine-enkephalin (MET) as well as calcitonin gene-related peptide (CGRP), substance P (SP) and pituitary adenylate cyclase-activating peptide (PACAP) was studied with immunohistochemistry. Almost all the neurons showed immunoreactivity to TH. Immunoreactivity to NPY, VIP, SOM, GAL, MET and PACAP was displayed by nerve cell bodies while nerve fibers exhibited immunoreactivity to all the neuropeptides studied. Therefore, it seems that the chemical coding of neurons and especially nerve fibers in the porcine intermediate ganglion share general similarities (with certain neurochemical variability), with porcine prevertebral ganglia (e.g., celiacomesenteric and caudal mesenteric ganglia). PMID- 21033572 TI - Efficacy of mepyramine maleate treatment in dogs with angioedema. AB - Twenty-seven dogs with angioedema, were enrolled in this clinical study. The cases were randomly assigned to the treatment group (n=15) and untreated placebo control group (n=12). It was concluded that mepyramine maleate has the potential to be helpful for dogs with angioedema. PMID- 21033573 TI - Comparison of the trabeculae structure of the spongy bone of the bilateral pastern bones in racehorses based on the imaging analysis of radiograms. AB - On the basis of a digital analysis of radiograms it was checked if, and to what extent, the extended loading of one of the sides of the body of racehorses leads to differences in the microstructure of the spongy bone of the bilateral pastern bones of the thoracic limbs. The research material consisted of radiograms of the pastern bones of the right and left thoracic limbs of racehorses. On the basis of computer image radiological analysis with the use of the "Trabecula,, programme, a quantative evaluation of the structure of the spongy bone of the pastern bones was conducted. It was noted that the differences between the right and the left pastern bones, despite extensive loading of the left thoracic limb, were not statistically significant as far as all studied parameters of the trabecula structure of the spongy bone were concerned. PMID- 21033574 TI - Mastitis and fertility disorders in cows. AB - Udder inflammations, independently of significant losses in milk yield and alteration of its quality, can negatively affect cows' reproduction efficiency. Mastitis causes changes in many active constituents, both in milk and blood. Pathogenic changes in existing constituents and new active chemical compounds, generated during disease, can affect other organs, particularly the reproductive system and its mechanisms. Fertility disorders in mastitic cows are mostly connected with the activity of cytokines (especially TNF-alpha), cortisol, prostaglandin F2-alpha, reactive oxygen species (ROS), and classic inflammatory mediators. The successful treatment of mastitis as well as protection against udder infections should be considered important methods for prophylaxis of fertility disorders in cows. The first Polish trials indicated that injection of supportive drugs (antioxidants or lysozyme dimer or flunixin meglumine) to intramammarily treated cows can increase fertility in cows with mastitis. PMID- 21033575 TI - Contemporary approach to acid-base balance and its disorders in dogs and cats. AB - The issue of the acid-base balance (ABB) parameters and their disorders in pets is rarely raised and analysed, though it affects almost 30% of veterinary clinics patients. Traditionally, ABB is described by the Henderson-Hasselbach equation, where blood pH is the resultant of HCO3- and pCO2 concentrations. Changes in blood pH caused by an original increase or decrease in pCO2 are called respiratory acidosis or alkalosis, respectively. Metabolic acidosis or alkalosis are characterized by an original increase or decrease in HCO3- concentration in the blood. When comparing concentration of main cations with this of main anions in the blood serum, the apparent absence of anions, i.e., anion gap (AG), is observed. The AG value is used in the diagnostics of metabolic acidosis. In 1980s Stewart noted, that the analysis of: pCO2, difference between concentrations of strong cations and anions in serum (SID) and total concentration of nonvolatile weak acids (Atot), provides a reliable insight into the body ABB. The Stewart model analyses relationships between pH change and movement of ions across membranes. Six basic types of ABB disorders are distinguished. Respiratory acidosis and alkalosis, strong ion acidosis, strong ion alkalosis, nonvolatile buffer ion acidosis and nonvolatile buffer ion alkalosis. The Stewart model provides the concept of strong ions gap (SIG), which is an apparent difference between concentrations of all strong cations and all strong anions. Its diagnostic value is greater than AG, because it includes concentration of albumin and phosphate. The therapy of ABB disorders consists, first of all, of diagnosis and treatment of the main disease. However, it is sometimes necessary to administer sodium bicarbonate (NaHCO3) or tromethamine (THAM). PMID- 21033576 TI - Bacteriophage receptors, mechanisms of phage adsorption and penetration into host cell. AB - Bacteriophages are an attractive tool for application in the therapy of bacterial infections, for biological control of bacterial contamination of foodstuffs in the alimentary industry, in plant protection, for control of water-borne pathogens, and control of environmental microflora. This review is mainly focused on structures governing phage recognition of host cell and mechanisms of phage adsorption and penetration into microbial cell. PMID- 21033577 TI - Interactions between Borrelia burgdorferi and mouse fibroblasts. AB - Borrelia burgdorferi spirochetes are an infectious agent of Lyme borreliosis. The aim of our studies was to investigate the fate of engulfed B. burgdorferi cells in L-929 mouse fibroblasts and to observe development of intracellular infection in vitro after 2 and 48 h. Electron microscopic studies reveal consecutive stages of B. burgdorferi spirochetes penetration to mouse fibroblasts in vitro. It has been observed, as a first step attachment and engulfment of spirochetes followed by formation of vacuoles. After 48 hours of infection, vacuoles of fibroblastic cells have been seen full of B. burgdorferi bacteria and latter they have been released from infected cells to extracellular space. It can be the evidence that B. burgdorferi multiply intracellulary. PMID- 21033578 TI - Clonal analysis of Staphylococcus aureus strains isolated in obstetric gynaecological hospital. AB - Epidemiological studies were carried out on 135 isolates of Staphylococcus aureus strains originating from medical staff, patients, and hospital environment. Restriction fragment length polymorphism (RFLP) analysis revealed genetic diversity of S. aureus isolates. Some clones were transmitted among nurses, doctors and patients. Our studies also demonstrate contamination of the hospital environment with S. aureus strains and there is a possibility that the patients acquire staphylococci from the environment. Moreover, we found that many medical staff workers were colonized with S. aureus and the transmission of these strains to patients is possible. PMID- 21033579 TI - Simultaneous detection and differentiation of pathogenic and nonpathogenic Leptospira spp. by multiplex real-time PCR (TaqMan) assay. AB - Leptospirosis, caused by pathogenic Leptospira, is one of the most important zoonoses in the world. Several molecular techniques have been developed for detection and differentiation between pathogenic and saprophytic Leptospira spp. The aim of this study was to develop a rapid and simple assay for specific detection and differentiation of pathogenic Leptospira spp. by multiplex real time PCR (TaqMan) assay using primers and probes targeting Leptospira genus specific 16S ribosomal RNA gene, the pathogen specific lig A/B genes and nonpathogen Leptospira biflexa specific 23S ribosomal RNA gene. Sixteen reference strains of Leptospira spp. including pathogenic and nonpathogenic and ten other negative control bacterial strains were used in the study. While the 16S primers amplified target from both pathogenic and non-pathogenic leptospires, the ligA/B and the 23S primers amplified target DNA from pathogenic and non-pathogenic leptospires, respectively. The multiplex real-time PCR (TaqMan) assay detection limit, that is, the sensitivity was found approximately 1 x 10(2) cells/ml for ligA/B gene and 23S ribosomal RNA gene, and 10 cells/ml 16S ribosomal RNA. The reaction efficiencies were 83-105% with decision coefficients of more than 0.99 in all multiplex assays. The multiplex real-time PCR (TaqMan) assay yielded negative results with the ten other control bacteria. In conclusion, the developed multiplex real-time PCR (TaqMan) assay is highly useful for early diagnosis and differentiation between pathogenic and non-pathogenic leptospires in a reaction tube as having high sensitivity and specificity. PMID- 21033580 TI - Methanogenic diversity studies within the rumen of Surti buffaloes based on methyl coenzyme M reductase A (mcrA) genes point to Methanobacteriales. AB - Methane emissions from ruminant livestock are considered to be one of the more potent forms of greenhouse gases contributing to global warming. Many strategies to reduce emissions are targeting the methanogens that inhabit the rumen, but such an approach can only be successful if it targets all the major groups of ruminant methanogens. Therefore, basic knowledge of the diversity of these microbes in breeds of buffalo is required. Therefore, the methanogenic community in the rumen of Surti buffaloes was analyzed by PCR amplification, cloning, and sequencing of methyl coenzyme M reductase (mcrA) gene. A total of 76 clones were identified, revealing 14 different sequences (phylotypes). All 14 sequences were similar to methanogens belonging to the order Methanobacteriales. Within Methanobacteriales, 12 clones (6 OTUs) were similar to Methanosphaera stadtmanae and the remaining 8 phylotypes (64 clones) were similar to unclassified Methanobacteriales. Overall, members of the Methanobacteriales dominated the mcrA clone library in the rumen of Surti buffalo. Further studies and effective strategies can be made to inhibit the growth of Methanobacteriales to reduce methane emission from the rumen which would help in preventing global warming. PMID- 21033581 TI - Optimisation of synthetic medium composition for levorin biosynthesis by Streptomyces levoris 99/23 and investigation of its accumulation dynamics using mathematical modelling methods. AB - The composition of a synthetic culture medium for levorin biosynthesis by Streptomyces levoris 99/23 was optimised using mathematical modelling methods. The optimal concentrations of the medium components were established by means of an optimum composition design at three factor variation levels. An adequate regression model was obtained. Levorin biosynthesis by Streptomyces levoris 99/23 in the optimised synthetic medium was over 38% higher than in the initial medium. The antibiotic biosynthesis dynamics in the optimised culture medium was studied by means of a non-linear differential equation system. The resultant model was valid. PMID- 21033582 TI - Chromate reduction by cell-free extract of Bacillus firmus KUCr1. AB - Microbial enzymatic reduction of a toxic form of chromium [Cr(VI)] has been considered as an effective method for bioremediation of this metal. This study reports on the in vitro reduction of Cr(VI) using cell-free extracts from a Cr(VI) reducing Bacillus firmus KUCr1 strain. Chromium reductase was found to be constitutive and its activity was observed both in soluble cell fractions (S12 and S150 and membrane cell fraction (P150). The reductase activity of S12 fraction was found to be optimal at 40 microM Cr(VI) with enzyme concentration equivalent to 0.493 mg protein/ml. Enzyme activity was dependent on NADH or NADPH as electron donor; optimal temperature and pH for better enzyme activity were 70 degrees C and 5.6, respectively. The Km value of the reductase was 58.33 microM chromate having a V(max) of 11.42 microM/min/mg protein. The metabolic inhibitor like sodium azide inhibited reductase activity of membrane fraction of the cell free extract. Metal ions like Cu2+, Co2+, Ni2+ and As3+ stimulated the enzyme but others, such as Ag+, Hg2+, Zn2+, Mn2+, Cd2+ and Pb2+, inhibited Cr(VI) reductase activity. PMID- 21033583 TI - Occurrence and characterization of Colletotrichum dematium (Fr.) grove. AB - Colletotrichum dematium was isolated from caraway for the first time in Poland in 2005. Isolations of this fungus were repeated in 2006 and 2007. The cultures of fungus were obtained from superficially disinfected leaves, root necks, roots, stems and umbels. The isolates were identified on culture media: PDA and malt agar with addition of pieces of caraway stems and on the base of macro and microscopic structures. Studies on the biotic effect between C. dematium and other species of phyllosphere fungi of caraway showed that the majority of the studied species limited the growth and development of C. dematium, but the size of the limiting effect was different. The species from Trichoderma and Gliocladium genera were the most effective against C. dematium, causing degeneration and lysis of hyphae and precluded the formation of the pathogen's acervuli and conidia. C. dematium in dual culture with E. purpurascens, A. radicina, S. sclerotiorum, B. cinerea and R. solani produced an inhibition zone which indicated its capacity for antibiosis. PMID- 21033584 TI - Cytotoxic activity of Serratia marcescens clinical isolates. AB - Twenty Serratia marcescens isolates from clinical specimens were examined for their cytotoxic activity on four cell lines (HEp-2, Vero, CHO, J774). Most of the isolates were found to be cytotoxic to CHO (70%), Vero (75%) and HEp-2 cells (90%). CHO cells were the most sensitive to cell-free supernatants, followed by HEp-2 and Vero cells. Two strains produced cytotonic toxins which caused elongation of CHO cells. Moreover, twelve isolates (60%) revealed cytotoxic potential to macrophage cell line J774. The results indicate that these bacteria may destroy phagocytes and epithelial cells, which may lead to spread within the host. PMID- 21033585 TI - Antibiotic susceptibility and genotype patterns of Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa isolated from urinary tract infected patients. AB - Thirty nine isolates of Escherichia coli, twenty two isolates of Klebsiella pneumoniae and sixteen isolates of Pseudomonas aeruginosa isolated from urinary tract infected patients were analyzed by antimicrobial susceptibility typing and random amplified polymorphic DNA (RAPD)-PCR. Antibiotic susceptibility testing was carried out by microdilution and E Test methods. From the antibiotic susceptibility, ten patterns were recorded (four for E. coli, three for K. pneumoniae and three for P. aeruginosa respectively). Furthermore, genotyping showed seventeen RAPD patterns (seven for E. coli, five for K. pneumoniae and five for P. aeruginosa respectively). In this study, differentiation of strains of E. coli, K. pneumoniae and P. aeruginosa from nosocomial infection was possible with the use of RAPD. PMID- 21033586 TI - rDNA-based genotyping of clinical isolates of Candida albicans. AB - The study presents an analysis of the restriction pattern ofrDNA fragments of 95 C. albicans isolates previously classified on the basis of the presence of the intron in rDNA into genotypes A (62 isolates), B (28), and C (5). Most isolates (61) with genotype A were classified as "subtype a" and one as "subtype d" (Karahan and Akar; 2005). No differences were observed in the restriction patterns of the tested genotype B isolates. Similarly, most genotype C strains (4/5) showed the same restriction pattern. The results indicate low subtyping variations of the analyzed isolates, which is in contrast to published data obtained from a Turkish collection of yeasts. PMID- 21033587 TI - Advanced thinking. PMID- 21033588 TI - Once in a generation overhaul is changing nurse education. PMID- 21033589 TI - An Olympian task. AB - Primary care trusts are being encouraged to boost the health and fitness of their employee and communities in the run-up to the Olympics. PMID- 21033590 TI - Changing young minds. AB - Primary school children in Devon are bein introduced to the profession. PMID- 21033591 TI - A mystery no more. AB - New research has solved one of the puzzles surrounding chronic fatigue syndrome, which could help in its future treatment. PMID- 21033592 TI - Unlocking potential. AB - Fiona Lydon is encouraging staff in a care home to challenge familiar approaches to practice and transform the lives of residents. PMID- 21033593 TI - Power of belief. PMID- 21033594 TI - An overview of pharmacology and acute pain: part one. AB - This two-part article, the fourth in a series on pain, explores the four main divisions of pharmacology: pharmacodynamics--what the medicine does to the body; pharmacokinetics--what the body does to the medicine; pharmacoeconomics--the cost and benefit ratio compared to other treatments; and pharmacovigilance--a medicine's safety profile. Part two, which will published next week, will explore the main categories of analgesic medicines. PMID- 21033595 TI - Support for men newly diagnosed with prostate cancer. AB - This article discusses the findings of a multi-hospital satisfaction survey of men with newly diagnosed prostate cancer. The survey was designed to enable direct comparison with a previously published satisfaction survey conducted by the Prostate Cancer Charity. Results showed that the nurse specialist is a valuable resource for patients and has an important role in maintaining standards of care. PMID- 21033597 TI - Diabetic ketoacidosis. PMID- 21033596 TI - Promoting positive approaches to dementia care in nursing. AB - This article provides an overview of factors relevant to dementia care today. The number of people experiencing dementia is increasing and dementia is at the forefront of health policy. The evidence base for person-centred approaches and interventions in dementia is expanding and nurses are central to implementing these across care settings. This is an exciting and challenging time for dementia care and nursing has a major role in leading and developing these changes in practice. The article discusses the importance of wellbeing and the Mental Capacity Act in assessing and caring for people with dementia. Psychosocial and pharmacological approaches to dementia care are described and the need to support carers of people with dementia is emphasised. PMID- 21033598 TI - Tales of a novice. PMID- 21033599 TI - An opportunity for change. PMID- 21033600 TI - Plan ahead, then you can have fun. PMID- 21033601 TI - Getting the dose right. PMID- 21033602 TI - Shhhhh...libraries have more to offer. PMID- 21033603 TI - Ethical, evidence-based guidelines for contraceptive use in research. PMID- 21033604 TI - When will we learn? PMID- 21033606 TI - The Czech audit: internal consistency, latent structure and identification of risky alcohol consumption. AB - AIM: The primary aim of the study is to examine the psychometric properties and the structure of the Czech version of the Alcohol Use Disorders Identification Test (AUDIT), and to estimate the rate of risky, harmful and problematic alcohol consumers. METHODS AND SAMPLE: Two large data sets were analyzed. The first was based on the application of the AUDIT as a part of a general population survey (N = 1.326; age range 18-64), the second represents data gathered by general practitioners (GPs) in the context of a pilot screening and brief advice (SBA) project in the area of Greater Prague (N = 2.589). RESULTS: Analyses of reliability showed satisfying internal consistency of the AUDIT (Cronbach's alpha = 0.83 for population survey and 0.77 for survey based on SBA). Principal component analyses suggest two factor solutions where one factor represents drinking patterns and the second alcohol-related problems or symptoms of dependence. The principal component analyses of both data sets led to similar factor formation. A total of 19% of the general population sample was classified as risky or harmful drinkers and 2% as problem drinkers. These figures were slightly lower in the sample of patients of general practitioners. CONCLUSIONS: The Czech version of the AUDIT seems to be a plausible screening instrument. The properties of the instrument suggest usefulness of the summary score for identification of the level of risk. PMID- 21033605 TI - IRBs and ethically challenging protocols: views of IRB chairs about useful resources. PMID- 21033607 TI - Alcohol consumption among men and women with tuberculosis in Tomsk, Russia. AB - Drinking behavior among Russian women remains poorly described. We analyzed gender differences in alcohol use among 374 tuberculosis patients in Tomsk, Siberia. Twenty-six (28.3%) women had lifetime alcohol abuse or dependence, compared with 70.6% of men. Women with alcohol use disorders drank 12.7 +/- 14.0 standard drinks per day and > or = 34.6% drank 2 three days per week. Among individuals with a lifetime alcohol use disorder, age of onset and typical consumption did not differ significantly by gender. We conclude that Russian women with alcohol use disorders consume almost as much alcohol as men and may be at greater risk for negative social and medical consequences. PMID- 21033608 TI - Cardiovascular risk predictors in central Slovakian Roma children and adolescents: regional differences. AB - The objective of the study was to determine some Cardiovascular Disease (CVD) risk factors in 174 Roma children and adolescents (88 males and 86 females) aged 7-18 in 3 Central Slovakian cities (44 from Zilina, 39 from Bansk, Bystrica and 91 from Rimavska Sobota). Venous blood samples were drawn in the morning, after a 12 hour overnight fast for biochemical analysis. Total cholesterol (TC) and triglycerides (TG) were determined enzymatically. HDL-cholesterol (HDL-C) after selective precipitation lipoproteins containing apolipoprotein B and LDL cholesterol (LDL-C) was calculated by the Friedewald Formula. Serum levels of apolipoproteins (apo A, apo B) were analyzed immunochemically. Concentration of lipoprotein a [Lp(a)] was analyzed by immunonephelometric method (Beckman-Coulter System). Anthropometric measurements, including weight, height, waist and hip circumference were used to calculate the sum of the body mass index (BMI) and waist to hip ratio (WHR). Measured blood pressure (BP) was used to classify for hypertension. Significant differences were determined in serum levels of LDL-C (p < 0.05; by Tukey HSD test multiple comparison more significant difference was determined between Zilina and Rimavska Sobota p < 0.046), TG (p = 0.008), apo A (p < 0.001), Lp(a) (p = 0.042), WHR (p < 0.001), BMI (p < 0.001), sBP (p < 0.001) and dBP (p = 0.012) in Roma individuals of all locality groups. The Roma population from Rimavsk, Sobota had (in comparison to the examined populations) statistically higher values of TC, TG, LDL-C, lower HDL-C. The population showed significant relation of TG and stress at home (p = 0.03) and at school (p = 0.01), HDL-C and cigarette smoking (p = 0.004), apo A and cigarette smoking (p = 0.02) and socioeconomic status (p = 0.006), WHR and cigarette smoking (p = 0.02). Risk values of WHR, apo B and Lp(a) were mostly determined in Zilina's population (WHR significantly connected with family history CVD p = 0.03, cigarette smoking p = 0.02 and leisure time physical activity p < 0.001) and BMI, apo A and BP in Banska Bystrica. WHR was positively correlated to BP and negatively to HDL-C and TG only in Roma participants from Rimavska Sobota. BMI was positively correlated to systolic BP in populations from Banska Bystrica and Rimavska Sobota. The results of the study should improve the paediatric health treatment and prevention of CVD risk predictors for Roma from different cities. PMID- 21033609 TI - Sense of coherence and health-related behaviour among university students--a questionnaire survey. AB - The aim of this study is to evaluate the relation between a sense of coherence and intensity of health-related behaviour among 521 Polish university students. The study was conducted using validated instruments with two questionnaires: Antonovsky's SOC-29 and the Inventory of Health-Related Behaviour. The mean value of SOC amounted to 125.2. More than half of the studied group were characterized by the average level of SOC. No statistical differences were found between the faculty of study and SOC (p = 0.107). A low intensity of health-related behaviour characterized a large group of students. Students of particular faculties differ among themselves in a statistically significant way in the level of health related behaviour (p = 0.015). SOC is related to healthy behaviour (p < 0.001). University students are often characterized by an average level of SOC and a low intensity of health-related behaviour. Medical students are characterized by higher level of health-related behaviour in comparison with humanistic and science students. SOC correlates positively with a tendency to health-related behaviour. The higher the level of coherence, the higher is the tendency towards pro-health behaviour. PMID- 21033610 TI - Prevalence and correlates of active traveling to school among adolescents in Cyprus. AB - More data regarding prevalence and correlates of active travel to school are needed from different parts of the world. The purpose of this study was to examine prevalence and correlates of active travel to school among adolescents in Cyprus. A cross-sectional study was conducted among 1966 adolescents attending grade 6, grades 7-9, grades 10-12 and technical/vocational schools in Cyprus. Overall prevalence of active travel to school was 19.4%. Parental perceptions of safe route to school, other children walking to school from the child's neighborhood and school location (urban versus rural) were associated with active travel across different levels of education. Having enough time to walk to school in the moming was the most consistent correlate of active travel. Low prevalence estimates of active traveling to school among adolescents in Cyprus raise the need to promote this source of daily physical activity. PMID- 21033611 TI - Recent epidemiological results of thyroid cancer in the most radiated territory in Poland. AB - In this report the authors evaluate epidemiological evidence of thyroid cancer cases in a highly radiated territory in Poland--i.e. in the province of Opole after 1986. The analysis - based on logistic regression modelling of registered thyroid cancer and an ecological covariate (137Cs concentration)--shows differences in incidence in six distinguished radiation zones and two equal periods. The results of this study indicate a significant increase in incidence of thyroid cancer in 1995-2002 in males and in females comparing to the years 1987-1994. Moreover, a considerable rise of incidences has been noticed in the elevated isotope's concentration zones in females across the province in the analyzed periods. The data comprises all the thyroid cancer cases registered in Opole province in the years 1987-2002. The data originated from the Provincial Cancer Registry in Opole. The information on 137Cs concentrations was derived from the Polish Geological Institute in Warsaw. The computation was performed using WinBUGS software. PMID- 21033612 TI - Varicose veins of lower extremities in pregnant women and birth outcomes. AB - The objective of the study was to estimate the association of pregnant women with varicose veins of lower extremities (VVLE) and the possible risk for adverse birth outcomes and among them different congenital abnormalities (CAs) in their children. Prospectively and medically recorded VVLE were evaluated in 332 pregnant women who delivered infants with CA (case group) and 566 pregnant women with VVLE who delivered infants without CA (control group) and matched to cases were compared in the population-based data set of the Hungarian Case-Control Surveillance System of Congenital Abnormalities, 1980-1996. About one-quarter of pregnant women had chronic VVLE while new onset VVLE occurred in the rest of pregnant women. There was no higher risk for adverse birth outcomes of pregnant women with VVLE, in fact the rate of preterm birth and low birth weight was somewhat lower than in the newborns of pregnant women without VVLE. The comparison of VVLE occurrence in pregnant women who had offspring with 21 different CA groups and in pregnant women who later delivered babies without CA showed a higher risk only for pectus excavatum, a mild CA. In conclusion, VVLE in pregnant women does not associate with obvious hazard for their fetuses. PMID- 21033613 TI - Effect of endurance exercise on resting testosterone levels in sedentary subjects. AB - OBJECTIVE: To investigate the effects of moderate-intensity and low frequency exercise on resting serum testosterone and cortisol levels, resting heart rate, and isokinetic strength among healthy sedentary young men. DESIGN: A randomized controlled study. Forty sedentary young men aged 18 to 25 years old, pedaled 50 minutes on a bicycle ergometry at 60% of maximal effort once a week for 12 weeks in an exercise group. OUTCOME MEASURES: Resting total and free serum testosterone, serum cortisol, anthropometric data, resting heart rate, and isokinetic strength during shoulder and knee extensions. RESULTS: Resting serum total and free testosterone, as well as cortisol did not differ significantly between groups. Neither group showed any significant changes in anthropometric data and isokinetic strength at the end of study. However, the resting heart rate of the exercise group reduced significantly after the training (p < 0.05). Also, the isokinetic strength of shoulder and knee significantly increased (p < 0.05). CONCLUSIONS: Twelve weeks of moderate-intensity and low frequency training had no effect on resting serum testosterone, but were sufficient to increase aerobic fitness among sedentary young men. The type of exercise training may encourage sedentary individuals to participate regularly in the program on physical activity. PMID- 21033614 TI - Healthcare-associated infections at intensive care unit of department of anesthesiology and intensive medicine at Martin Faculty Hospital. AB - We analyzed the occurrence of healthcare-associated infections (HAl) at intensive care unit of the Department of Anesthesiology and Intensive Medicine of Martin Faculty Hospital in 2008. We performed a retrospective-prospective observation according the protocol of European HELICS (Hospital in Europe Link for Infection Control and Surveillance) system. We found 11 HAl (4.45%) which on average prolonged the length of hospitalization by 6 days. The most frequent localisation of HAl was the respiratory tract. By our own observation we found the same number of HAl cases as it had been reported officially but the observed and reported cases do not match. The surveillance system HELICS uses definitions slightly different from those used in Slovakia. The severity of health status of a patient at admission influences the risk of HAl. We suggest a continuing collaboration on HELICS system with further involvement of all departments of Martin Faculty Hospital and creation of a hospital infection control team. We also suggest an improvement in testing for etiologic agents of HAl and an introduction of methods of molecular epidemiology in diagnostics, as well as quantification of costs related to occurrence of HAl and to assess an implication of automated monitoring system in HAl surveillance. PMID- 21033615 TI - The Joint Commission moving to link accountability to accreditation. PMID- 21033616 TI - CMS updates guidelines on anesthesia services. PMID- 21033617 TI - Should you post, text your ED wait times? PMID- 21033618 TI - Full disclosure may equal decreased claims. PMID- 21033619 TI - Understanding three types of human errors. PMID- 21033620 TI - MCP-1 -2518 A/G gene polymorphism is associated with blood pressure in ischemic heart disease asymptomatic subjects. AB - Monocyte chemoattractant protein-1 (MCP-1), one of the key inflammatory chemokines, plays an important role in the initiation of atherosclerosis, and represents a risk for coronary artery disease and myocardial infarction. A recent animal study showed that MCP-1 gene might be a candidate gene for salt-sensitive hypertension in Dahl salt sensitive rats. This effect has not been yet studied in asymptomatic humans. We tested the MCP-1 -2518 A/G single nucleotide polymorphism (SNP) in 66 hypertensive ischemic heart disease asymptomatic subjects. Inflammatory markers, classic risk factors and absolute cardiovascular risk (SCORE system) were also investigated in these subjects. Our results showed that both, systolic and diastolic values of blood pressure were associated with MCP-1 2518 A/G SNP at the level of both, genotype and allele frequencies. Subjects with mutant G allele had higher levels of both values of blood pressure, systolic (p = 0.035) and diastolic (p = 0.040) than subjects with allele A. Statistically significantly higher levels of both values of blood pressure, systolic (p = 0.037) and diastolic (p = 0.021) were found also in IHD asymptomatic subjects with AG and GG genotypes. Subjects with AG and GG genotypes had also an increased absolute cardiovascular risk (1.62% vs 3.17%; p = 0.004) and an increasing trend for elevated plasma level of high-sensitive CRP (2.858 vs 2.062 mg/l; p = 0.076). We did not find any significant correlation between the serum level of MCP-1 and blood pressure. To our best knowledge, this is the first study concerning the association between MCP-1 polymorphism and arterial blood pressure in IHD asymptomatic subjects. These results indicate that the expression of MCP-1 may be increased before the onset of hypertension but further observations from larger cohorts are needed to confirm this finding (Tab. 6, Ref. 41). PMID- 21033621 TI - Piperine, active substance of black pepper, alleviates hypertension induced by NO synthase inhibition. AB - OBJECTIVES: The presented study is aimed on exploring the effects of black pepper on blood pressure in the rat model of experimental hypertension induced by chronic NO synthesis inhibition. BACKGROUND: Piperine, the compound of black pepper, can cause a significant decrease of blood pressure in normotensive rats possibly via calcium channel blockade, a pathway that is known to be effective in prevention of L-NAME (N(G)-nitro-L-arginine methyl ester) induced hypertension. METHODS: Wistar rats were administered clear water (C), L-NAME (40 mg/kg/day, L), piperine (20 mg/kg/day) in corn oil by oral gavage with L-NAME (LP) or without it (P) for 6 weeks. The systolic blood pressure was measured weekly. Specimens of thoracic aorta were processed in paraffin and histological slices were stained with hematoxylin and eosin, Mallory's phosphotungstic acid hematoxylin (PTAH), orcein, antibodies against inducible NO synthase (iNOS) and smooth muscle cells actin (SMCA). Microscopic pictures were digitally processed and morphometrically evaluated. RESULTS: L-NAME increased the blood pressure, cross-sectional area of aorta, media thickness, elastin and SMCA synthesis and PTAH positive myofibrils relative and absolute content in the aortic media, wheras it decreased percentual content of iNOS, elastin and SMCA. Piperine decreased the blood pressure rise from the third week of treatment, synthesis of elastin and the percentual and absolute content of PTAH positive myofibrils, however, it did not affect other parameters. CONCLUSION: Oral administration of piperine is able to partially prevent the increase of blood pressure caused by chronic L-NAME administration. This effect is probably caused by the blockage of voltage-dependent calcium channels and supported by filamentous actin disassembly (Tab. 1, Fig. 2, Ref. 35). PMID- 21033622 TI - Specificity and sensitivity of differentiation antigens in superficial soft tissue tumors: comparison of SMA, calponin, H-caldesmon, C-kit, PLAP and HPL. AB - We examined the expression pattern of smooth muscle actin (SMA), h-caldesmon (HCD), calponin (CALP), placental alkaline phosphatase (PLAP) and human placental lactogen (HPL) in benign and malignant spindle cell superficial soft tissue tumors in order to determine the role of these markers in differential diagnosis. Archival tissue from 38 patients with superficial smooth muscle cell and so called fibrohistiocytic tumors (8 benign fibrous histiocytomas (BFHs), 6 dermatofibrosarcoma protuberans (DFPT), 9 malignant fibrous histiocytomas (MFHs), 9 leiomyomas (LMs) and 6 leiomyosarcomas (LMSs)) were immunostained with antibodies against SMA, HCD, CALP, PLAP and HPL. smooth muscle cell (SMC) tumors showed significantly high immunopositivity for HCD than that of so-called fibrohistiocytic tumors (p is less than or equal to 0.05) but 1/3 of DFPT and MFH cases and half of BFH cases also showed HCD immunopositivity; thus, this difference is debatable and not highly discriminative as expected. All tumor groups showed 100% immunopositivity for CALP. SMC tumors displayed significantly stronger and more widespread immunostaining pattern for PLAP than so-called fibrohistiocytic tumors (p < 0.05). Superficial soft tissue tumors did not express c-kit. In conclusion, HCD and PLAP can be used as ancillary immunomarkers in differential diagnosis of SMC tumors (Tab. 2, Fig. 7, Ref. 37). PMID- 21033623 TI - Imbalance of VEGF family serum levels and receptors in patients with inflammatory bowel disease. AB - The aim of this study was to analyze the serum levels and prognostic significance of vascular endothelial growth factor (VEGF)-A, -C, and -D, and their receptors, VEGFR-1 and -2 in inflammatory bowel disease (IBD). The serum levels of VEGF family members were measured in 80 control subjects and 200 patients with inflammatory bowel disease using an enzyme linked immunosorbent assay (ELISA). These measurements were evaluated with regard to the levels of inflammatory markers, such as C reactive protein (CRP) and serum amyloid A (SAA) and the clinical characteristics of patients, so that potential correlations could be recorded. A correlation between VEGF and their receptors serum levels is present in IBD patients. These new findings open the question on the potential role of VEGF and their receptors in IBD (Tab. 2, Ref. 9). PMID- 21033624 TI - Protection of ovarian tissue from radiotherapy. AB - Advances researches in the diagnosis and treatment of childhood, adolescent and adult cancer have greatly increased the life expectancy of premenopausal women with cancer. However, one of the serious side effects of these treatments is the risk of damage to fertility. The ovaries are very sensitive to cytotoxic and radiotherapeutic treatment. The only established method of fertility preservation is embryo cryopreservation according to the Ethics Committee of the American Society for Reproductive Medicine (2005), but this option requires the patient to be of pubertal age, have a partner or use donor sperm, and be able to undergo a cycle of ovarian stimulation, which is not possible when the radiotherapy has to be initiated immediately or when stimulation is contraindicated according to the type of cancer. For patients who need immediate radiotherapy, cryopreservation of ovarian tissue is the only possible alternative. This manuscript reports the different techniques of cryopreservation and the results of transplantation of cryopreserved ovarian tissue. The current techniques allow cryopreservation of human ovarian fragments for a long time with good follicular survival rate after thawing. Numerous studies ultimately in this field have demonstrated to improve the survival rate of the oocytes and cryopreserved follicles. Moreover this manuscript includes a case of a 17-year-old girl who had to undergo pelvic irradiation for non-Hodgkin's lymphoma and the laparoscopic treatment to preserve the fertility (Fig. 2, Ref. 47). PMID- 21033625 TI - Physical therapy of non-neurogenic voiding dysfunction in children with occult spinal dysraphism. AB - BACKGROUND: In children with occult spinal dysraphism one of the symptoms is disbalance in bladder emptying and filling. Goal of our study was to estimate the correlation of medicamentous treatment alone and combined medicamentous and physical treatment in patients that are diagnosed with occult spinal dysraphism with non-neurogenic bladder dysphunction. METHODS: We evaluated 69 patients aged from 4 to 12 years treated at the University children's Hospital in Belgrade during 2005-2008 years period. In the first group of 29 patients only medicamentous therapy was implemented. In the second group of 40 patients combined medicamentous and physical therapy were applied. Physical therapy methods that were used included: transcutaneal electric nerve stimulation and exponential current. We monitored daily enuresis, enuresis nocturna, urgency and frequency. Urodynamic evaluation included: bladder capacity, onset of unstable contractions, residual urine and detrusor sphincter dyssynergia. RESULTS: Statistical analysis showed that there is significant improvement (p < 0.001) in all evaluated symptoms after 6 months and for urgency there was significant improvement (p < 0.05) after 3 months from the beginning of the treatment with combined therapy. Our study pointed out significant improvement in the group treated with combined therapy for detrusor sphincter dyssynergia and unstable contractions after 3 months while after 6 months from the beginning of the treatment there was significant improvement (p < 0.001) for all urodynamic parameters. CONCLUSIONS: Combined medicamentous and physical treatment is more beneficial for patients with non-neurogenic bladder instead of medicamentous treatment alone (Tab. 2, Ref. 11). PMID- 21033626 TI - Garlic (Allium sativum L.) and cardiovascular diseases. AB - Garlic is an important component in the complementary and alternative medicine. Large segments of population believe in and utilize herbal products even when these have not been as thoroughly researched as garlic. Experimental and clinical studies confirm that the ancient experience with beneficial effects of garlic holds validity even in prevention of cardiovascular disorders and other metabolic ills. Most recent data published after year 2000 convincingly point out that garlic and its various forms reduce cardiovascular risk, including abnormal plasma lipids, oxidized low density lipoproteins (LDL), abnormal platelet aggregation and a high blood pressure. Stimulation of nitric oxide generation in endothelial cells seems to be the critical preventive mechanism. Garlic may promote an anti-inflammatory environment by cytokine modulation in human blood. Cardioprotective effects of dietary garlic are mediated in large part via the generation of hydrogen sulfide (H2S). Garlic-derived organic polysulfides are converted by erythrocytes into hydrogen sulfide which relaxes vascular smooth muscle, induces vasodilation of blood vessels, and significantly reduces blood pressure. There are data on potential ability of garlic to inhibit the rate of progression of coronary calcification. Garlic as a dietary component appears to hold promise to reduce the risk of cardiovascular disease (Fig. 2, Ref. 46). PMID- 21033628 TI - Sandwich mesh abdominal closure. AB - The open abdomen carries a high mortality rate and represents a big surgical challenge. The recent introduction of vacuum assisted closure (VAC) introduced new techniques of its management, including STAR--Staged Abdominal Repair, Fabian Protocol, VAC supported with PDS, support with polyglactin mesh and the use of tissue expanders in the staged closure of the open abdomen. One of the methods, SMAC--sandwich mesh abdominal closure, emerged in April 2008 by the clinical group from Germany. The authors present their own modification of SMAC and a case report, where it was used. By current literary research it was the first patient in the Central European hospital managed by SMAC VAC. The authors of the article conclude that SMAC VAC and its modification is highly effective in the management of the open abdomen (Fig. 5, Ref. 4). PMID- 21033627 TI - Sexual dysfunction in females treated with peripheral blood progenitor cell transplantation: review of literature. AB - BACKGROUND: Peripheral blood progenitor cell transplantation (PBPCT) is a therapeutic modality used in the anti-tumorous treatment of hemato-oncological diseases and solid tumors. Apart of that, it is also used in therapy of non malignant and hereditary diseases. AIM: As is the case with other treatments, PBPCT also affects not only the disease process but also the quality of life (QoL). MATERIALS AND METHODS: In the last decade of 20th century, several QoL studies among patients treated with PBPCT were undertaken and an influence on particular dimensions of QoL was observed. One of closely watched aspects was sexuality in patients treated with PBPCT. RESULTS: Sexuality and its expression belong to very important aspects of human behavior. It is also a very sensitive and sensible aspect, so with no doubts it is affected by the diagnosis of neoplasm and cancer treatment. CONCLUSION: Physical and psychosocial factors of PBPCT do affect patient's sexuality and sexual functioning as part of QoL. They remain in focus because of the complex care of patients treated with PBPCT (Fig. 2, Ref. 21). PMID- 21033629 TI - Abdominal and pelvic hydatid cyst obstructing the labor. AB - Hydatid cystic disease is a parasitic disease primarily infesting the sheep and cattle. It is a rare condition in pregnancy with an incidence of 1/20000 pregnancies. An eighteen-year-old primigravida was evaluated due to obstructed labor. Multiple abdominal and pelvic hydatid cysts were diagnosed by ultasonography and a healthy infant with birthweight of 3330 g was delivered by cesarean section. While the cysts situated on the posterior uterine wall, paraovarian region and omentum were removed totally, the hepatic cysts were only partially removed and then drained. The hydatid disease should be considered in differential diagnosis of adnexal masses obstructing the labor in pregnancy (Fig. 3, Ref. 9). PMID- 21033630 TI - A case with an asymptomatic malformation of cortical development diagnosed in eighth decade of life. AB - We report a patient newly diagnosed with cortical dysplasia upon magnetic resonance imaging (MRI) in his eighth decade of life after a recent syncopal attack. The neurological examination and laboratory findings were normal. His cranial MRI revealed a lesion giving a low signal on T1-weighted images, which was evaluated as focal cortical dysplasia. No treatment was given, and he did not have any further syncopal or epileptic attacks during the subsequent two-year follow up. No previous study has described such a case of malformations of cortical development (MCD) in patients older than 70. Especially in asymptomatic or clinically less severe patients, the underdiagnosis of MCD may result in a clinical spectrum that is too narrow to reflect the reality (Fig. 1, Ref. 6). PMID- 21033632 TI - "Water cooler" learning: knowledge sharing at the clinical "backstage" and its contribution to patient safety. AB - PURPOSE: This paper seeks to identify the instances of informal knowledge sharing at the "backstage" of the clinical environment and to demonstrate their contribution to organisational learning and patient safety. DESIGN/METHODOLOGY/APPROACH: The approach takes the form of an ethnographic study in two Day Surgery Units in the UK National Health Service undertaken over three months in various clinical and non-clinical settings. The observations recorded the instances of communication and knowledge sharing, as well as taking into account the wider socio-cultural and organisational context. FINDINGS: The study identified situations of informal knowledge sharing. These were characterised by degrees of homogeneity/heterogeneity and patency/privacy. Focusing on three sites -staff lounge, storeroom, and theatre corridor, the paper elaborates the context and content of knowledge sharing, and the contributions to clinical practice, service function and learning. PRACTICAL IMPLICATIONS: Backstage knowledge sharing is premised on shared understanding, trust and mutuality and situational opportunity. This contrasts with more formal models of learning advocated in policy. Services managers might embrace, rather than replace, these relationships, whilst emphasising the need for knowledge to be shared more widely amongst peers and service leaders. ORIGINALITY/VALUE: To date, little research in the area of patient safety has considered the contribution of informal learning at the "backstage". This is an important, if taken-for-granted, part of everyday practice and makes a "hidden" contribution to organisational learning. PMID- 21033631 TI - Squamous cell carcinoma secondary to Buruli ulcer: a clinical case report in a young girl. AB - Buruli Ulcer, a common tropical disease, is endemic in West Africa in particular in Cote d'Ivoire, where it represents the second mycobacterial disease after Tuberculosis. The late diagnosis and treatment as well as, the lack of surveillance, lead to large skin ulcerations, local or multifocal osteomylitis and some time it may lead to neoplasia which contribute to worse the prognosis of the patient. We presented a case report in a girl of 16 years old, who died from an aggressive squamous cell carcinoma of the upper limb secondary to Buruli Ulcer. This case report showed the importance of early detection and treatment, a specific surveillance for Buruli Ulcer infected patients, a need for them to be vigilant and to report any suspected skin lesions even after healing, and the need for a good prevention strategy in Buruli Ulcer endemic areas. PMID- 21033633 TI - Don't stop the clock: manipulating hospital waiting lists. AB - PURPOSE: This paper aims to explore the theoretical and practical management implications of a case involving the falsification of hospital patient waiting lists for elective orthopaedic surgery. DESIGN/METHODOLOGY/APPROACH: This case study is based on qualitative schedule-structured interviews with 20 senior hospital staff (managerial and clinical), including the head of the investigation team, downloads from the hospital website, and internal hospital documentation. Those data were used to construct an event narrative exploring the underlying causes and implications of the incident. FINDINGS: The blame for misconduct pointed at three surgeons, a senior manager, a general manager, an assistant general manager, one administrative staff member, and several organizational factors. In addition to censuring some of those involved, an investigation recommended changes to training and working practices, policies and procedures, governance arrangements, and organization culture, and led to an external evaluation of the hospital board. However, one year later, another similar incident occurred. RESEARCH LIMITATIONS/IMPLICATIONS: This is a single case, and events are viewed through a management lens, the individuals concerned being protected by research ethics considerations. PRACTICAL IMPLICATIONS: By detailing the sequence of events, surrounding conditions, and the reactions of multiple players, this analysis reveals typified responses to incidents of this kind, and the limitations inherent in post-event investigations. If the benefits derived from national targets are to be realized in a manner which commands support from staff at all levels, then greater attention should be paid by managers and regulators to issues of transparency, responsiveness, and honesty. As core dimensions of good governance, managers must be accountable for helping to meet targets, and also for tracking how targets are met, ensuring that resources are made available, and that problematic issues raised are promptly and effectively addressed. ORIGINALITY/VALUE: Studies of organizational misbehaviour are rare in healthcare where the focus often lies with patient deaths and injuries arising from system failures and gross individual misconduct. The analysis in this case explores the organizational conditions that contribute to such incidents. PMID- 21033634 TI - Understanding the effect of decentralisation on health services: the Nepalese experience. AB - PURPOSE: Despite enormous progress in health globally, primary healthcare services in many developing countries are facing different challenges. Many studies have documented that decentralisation could be useful in supporting and developing health services closer to citizens. The purpose of this paper is to assess the effect of decentralisation on health services, and to draw general lessons which might help to develop appropriate strategies to improve health services in Nepal. DESIGN/METHODOLOGY/APPROACH: A mixed method was used, consisting of reviews of current literatures relevant to decentralisation and health performance, engaging with health service inputs-outputs data between 2001 and 2007, and assessing the range of choices (management, finance and governance) available to local authorities using Bossert's "decision-space approach". FINDINGS: Decentralisation in many countries, including Nepal, suggests a new form of service delivery. ORIGINALITY/VALUE: Review of the selected studies in triangulation with health services data has revealed that decentralisation in many cases has improved access to, utilisation of, and management of health services. The effects on other performance dimensions such as policy, equity, quality and service effectiveness are poorly investigated topics in the literature. The findings suggest that the successful implementation of decentralisation requires a broader context of institutional capacity building and resource management, and underlines the need for their consideration during implementation processes, and further investigation. PMID- 21033635 TI - The role of learning and customer orientation for delivering service quality to patients. AB - PURPOSE: This study seeks to investigate the impact that learning orientation, internal and external customer orientation have on quality of care delivered to patients. Additionally, given the differences between managerial and non managerial employees regarding organizational value perception and focus on the needs of internal customers and patients, the study aims to examine potential variations in these relationships. DESIGN/METHODOLOGY/APPROACH: The study took place in ten out of 31 public hospitals operating in the five largest districts in continental Greece. Hospitals were chosen on a random basis. Out of 800 questionnaires that were personally administered, 499 usable responses were gathered. FINDINGS: The extent to which employees create and use knowledge and focus on satisfying the needs of both internal customers and patients is indicative of the quality of care provided. In addition, only managerial employees believe that learning orientation reinforces quality of care. RESEARCH LIMITATIONS/IMPLICATIONS: The fact that employees rated quality of care delivered to patients and that most employees had extended tenure should be taken into consideration when interpreting these findings. PRACTICAL IMPLICATIONS: Top management needs to create a strong and clear culture that emphasizes learning, as well as internal customer and patient orientation, and infuse them among all organizational members. Moreover, human resource management policies should be aligned to meeting or exceeding patients' requests and expectations. ORIGINALITY/VALUE: The paper enhances existing knowledge with regard to the antecedents of offering medical care of high quality. PMID- 21033636 TI - Mutualism and antagonism within organisations of integrated health care. AB - PURPOSE: The purpose of this paper is to explore the concepts of Swedish integrated health care, their state of development and interdependence, and, furthermore, evaluate whether the theoretical framework used improves the comprehension of why integrated health care arrangements endure or cease. DESIGN/METHODOLOGY/APPROACH: The study is founded on descriptive data gathered from a literature search on integrated health care in Sweden. With inspiration from ecology theory, these data were analysed guided by a theoretical model based on a continuum of symbiotic effects, from antagonism to mutualism. FINDINGS: The era of Swedish integrated health care started in the 1990s, when a kind of clinical network called chains of care was launched. At the beginning the chain of care development was predominantly surrounded by non-integrative conditions, which had a restraining effect on these efforts. Even so, it seems that chains of care are here to stay. This faith in chains of care can to some extent be explained by the crucial role they have as connectors in the emerging local health care systems. Thus, these systems need chains of care to evolve and chains of care seem to require the integrative framework of local health care to progress and endure. Integrated health care performance could be troublesome, unless such mutualistic conditions are in place. States of commensalism may also be promoted, but the advantages are unilateral and therefore there is a risk of disloyalty by the unaffected part, which, in turn, can create a breeding-ground for an antagonistic liaison. ORIGINALITY/VALUE: A theoretical approach founded on what may be called "Health Care System Ecology" appears to enhance the understanding of the complex logic of integrated health care. PMID- 21033637 TI - From artefact to effect: the organising effects of artefacts on teams. AB - PURPOSE: Earlier studies have identified artefacts, but have only to a lesser degree looked at their effects. The purpose of this paper is to investigate how artefacts contribute to organisation. DESIGN/METHODOLOGY/APPROACH: A trauma team at a university hospital has been observed and its members interviewed. FINDINGS: The trauma team showed itself to be rich on artefacts since it had strong internal driving forces, high legitimacy, and tried to live up to high expectations from the outside. Its members were motivated to be in the forefront of trauma care. Through renewal, the team succeeded in maintaining demarcation. It also succeeded in systemising internal work tasks and made for itself a position in relation to the outside. The team's capacity, however, came to be limited by internal conflicts and battles for prestige. PRACTICAL IMPLICATIONS: The study shows that informal logic has a strong influence on teams. Teamwork contributed to the development of organisational structure and motivation for the personnel. ORIGINALITY/VALUE: Earlier studies advocate the important role of artefacts in order to communicate, collaborate, negotiate or coordinate activities. The conclusion is that artefacts also have an organising and developing effect on teams in a fragmented and differentiated healthcare. PMID- 21033638 TI - The passing of the Nuffield Institute for Health at the University of Leeds. PMID- 21033639 TI - Five have a leadership adventure: exploring childhood fictional influences on the construction of self as a leader. AB - PURPOSE: This study proposes to examine whether tales from childhood influence the psyche and self of the adult in their professional role as a leader in a large organization. It is positioned within a social constructionist and postmodernist framework. DESIGN/METHODOLOGY/APPROACH: The methodology development was challenging; to capture the level of abstraction within which it was positioned. Using narrative inquiry allowed for a less rigid methodology, data collection and analysis. The data were collected using a non-structured single interview with a known subject, the data analysed using an initial thematic analysis followed by an in-depth analysis of the themes against the background of an Enid Blyton novel. FINDINGS: This research project has shown how all are products of their whole life experiences to date; thus the tales from childhood must also impact on adult lives. This project identified links between the adult professional self and the characters in the tales, which were read as children. Leadership can be read as an adventure story or fairy tale, a myth born out of the narratives and language often used to describe it, reflecting tales of quest and achievement. ORIGINALITY/VALUE: The interpretations on offer are only one version; another reader or teller would experience a different interpretation; finding her own story, while constructing herself as a researcher, was unexpected and surprising. There are at least two stories running throughout predominantly: the subjects' story and the story of the research. PMID- 21033640 TI - Enterprising health: creating the conditions for entrepreneurial behaviour as a strategy for effective and sustainable change in health services. AB - PURPOSE: This paper seeks to investigate conditions under which entrepreneurs emerge as agents of effective and sustainable change in UK National Health Service Trusts. DESIGN/METHODOLOGY/APPROACH: The research synthesises literature on changing regulatory structures ("post-bureaucracy") and entrepreneurial behaviour to understand how individual identity construction is informed both by context and by individual attributes. Thematic analysis of interview data involving managers from 11 NHS Trusts, including detailed analysis of six transcripts, focuses on regulatory processes, the emergence of entrepreneurial behaviour and outcome variations in workplace innovation and improvement. FINDINGS: This study identifies co-existing modes of regulation, which interact with individual behaviour, generating strategies differentiated as entrepreneurial or conformist. Four ideal types are identified: organisational entrepreneurship, resisted or dissonant entrepreneurship, conformity, and symbolic entrepreneurship. Analysis reinforces those literature findings, which suggest that the interaction of regulatory structures and the identity work of individuals influence the emergence of entrepreneurial behaviour and the effectiveness of change. PRACTICAL IMPLICATIONS: The ability to achieve effective and sustainable outcomes varies considerably even between NHS Trusts faced with comparable challenges in implementing nationally prescribed targets. This variance is explained in terms of the organisation's ability to generate the structures, processes, individual competence and motivation which enable employees at all levels to act entrepreneurially with the ability and legitimacy to achieve strategic goals by working creatively in the spaces between formal organisational structures. ORIGINALITY/VALUE: The study identifies specific conditions, which stimulate the emergence of entrepreneurs as agents of effective and sustainable change in the NHS, identifying factors that policymakers should consider when implementing change. PMID- 21033641 TI - "Young women's voices and HIV/AIDS in Uganda". PMID- 21033642 TI - HIV prevention for young women of Uganda must now address poverty and gender inequalities. AB - PURPOSE: This study seeks to explore the perspectives of young women in Uganda with the aim of better informing re HIV prevention. DESIGN/METHODOLOGY/APPROACH: Group discussions and interviews were used to explore issues relating to HIV prevention. An inductive content analysis identified emerging themes and patterns in the participants' conversations. FINDINGS: The study revealed that, although young women were informed and motivated to prevent HIV, poverty and inequality were significant barriers, limiting their power to protect themselves. ORIGINALITY/VALUE: The research adds evidence to the current argument that failure to address the disempowering effects of poverty and gender inequality limits the effectiveness of current HIV prevention for young women. HIV prevention must now address poverty and gender vulnerabilities, promoting a protective environment, rather than focusing on influencing individual sexual behaviour. PMID- 21033643 TI - Perceptions of sexual coercion among young women in Uganda. AB - PURPOSE: This paper sets out to explore Ugandan young women's definitions and perceptions of sexual coercion. DESIGN/METHODOLOGY/APPROACH: A qualitative study was conducted with seven young women in rural Uganda. Participants filmed videos, wrote stories, made drawings and participated in transect walks before analysing their data through formal and informal discussions. FINDINGS: Forced sex is defined narrowly to mean only rape. Verbal forms of sexual coercion were recognised, but only after some discussion. Verbal coercion is referred to as "abusing" or "convincing". Young women are commonly pressured into consenting to have sex, despite what they really want, owing to the socio-cultural circumstances. Young women in Uganda are significantly tolerant of sexual coercion. This tolerance appears to arise from power differentials between genders, and the socio-cultural environment shaping their lives. ORIGINALITY/VALUE: The paper improves understanding of young women's definitions and perceptions of sexual coercion, which is essential to provide effective violence prevention programmes. It also suggests that further research is warranted in this field. PMID- 21033644 TI - Life experiences and expectations of young women in Uganda. AB - PURPOSE: This study aims to explore the life experiences and expectations of young women of Busoga in Eastern Uganda. DESIGN/METHODOLOGY/APPROACH: Using qualitative methods, a small group of young women drew, wrote stories and made videos together. The data which emerged from this exercise were analysed alongside the researcher's own observations. FINDINGS: Basoga society's main expectation of young women is that they will work in the home. Yet, young women describe very different ideas of what they want from their lives; this includes a desire for access to a good educational experience, and different expectations for family life than cultural norms. They find, however, that there are many barriers to meeting those expectations. ORIGINALITY/VALUE: The study is important because it acknowledges and forefronts Ugandan young women's life expectations. Typically, development focuses on "outsider" considerations rather than "insider" views and desires. The desires of the marginalised, such as young women in Africa, are a particularly neglected subject. There is a need for continued efforts to explore and include young women's experiences and expectations countering gender inequality and as part of ongoing gender empowerment and sexual health strategies. PMID- 21033645 TI - Something-for-something love: the motivations of young women in Uganda. AB - PURPOSE: This paper aims to explore the motivations of young women in Busoga, Uganda, engaging in "Something-for-something" love (SFSL) relationships. Something-for-something love is defined as engaging in sex in exchange for money, favours, gifts and goods. This paper examines whether these relationships affect young women's ability to negotiate safe sex. DESIGN/METHODOLOGY/APPROACH: Qualitative methods were used with a group of six young women including participatory video, drawing, stories and life histories. In addition, semi structured interviews were conducted with each participant and two key informants. Data were analysed using an inductive thematic approach. FINDINGS: Peer pressure, financial gain, school fees, basic needs and family pressure were key motivations for SFSL. Power dynamics embedded in Ugandan local culture were found to play a significant role in SFSL and family pressure is suggested to assume a greater role than previously perceived. Transaction was considered to be part of what was expected within a "natural romantic relationship". Condom use was less likely in relationships where a great amount of gifts were exchanged, as men were more likely to negotiate sex on their terms, and this often led to unprotected sex. ORIGINALITY/VALUE: The study contributes much-needed insight into motivations behind young women participating in SFSL. Young women involved in such relationships are portrayed along a spectrum ranging from vulnerable to empowered. The study emphasises the role parents and other kin play in influencing their children's sexual and reproductive health choices. The study highlights to policy makers that interventions aimed at improving parent-child communication are needed; as well as a more informed approach to HIV prevention, taking onboard the complexities of SFSL. PMID- 21033646 TI - Multiple sexual partners: perceptions of young men in Uganda. AB - PURPOSE: This study seeks to explore the perceptions of young men in Uganda regarding their sexual behaviour, which is normally understood as "high risk" in terms of HIV/AIDS. Specifically, the paper aims to look at the practice of engaging with multiple sexual partners (MSP). DESIGN/METHODOLOGY/APPROACH: Six 15 19 year old school-going young men in rural Uganda played an attribute-ranking game, wrote personal stories and acted in small dramas as part of the data collection. FINDINGS: The participants of the study spoke about love and sex being important in a relationship, which is why they engaged in MSP, to maximise their experience of both. MSP also allowed the young men to gain pleasure, experience and control: three necessary and sought-after attributes inherent in their notion of masculinity. The features that challenged these three factors (i.e. money, manipulative girls, parental control), which threatened their ideals of masculinity, were identified by participants as the primary risks of MSP, rather than health threats. ORIGINALITY/APPROACH: A more open-minded and positive emphasis is needed regarding the use of condoms, where pleasure and issues of "manliness" are incorporated. By understanding the experiential views of young men, HIV/AIDS prevention programmes can be adapted accordingly to better reflect their lived realities. PMID- 21033647 TI - Taking account of what young women want from school sex education: two groups from Scotland and Uganda. AB - PURPOSE: This study seeks to explore what young women want from their school based sex education. DESIGN/METHODOLOGY/APPROACH: Qualitative methods were used to explore the perspectives of two groups of young women from Uganda and Scotland. FINDINGS: Of particular importance to all the young women were: a diverse sex education curriculum appropriate to the ages of the students, being taught by an outside female facilitator, single-sex classes and access to a female teacher. Furthermore, they proposed that discussion between small groups of friends is very useful. The Scottish group said that having a young teacher, teaching about emotions and relationships and being guided through their own decision making is also important. The Ugandan group emphasized the importance of being taught by female family members and having written materials provided on sex education. ORIGINALITY/VALUE: The study showed that young women from different backgrounds have strong opinions about sex education, and are an important resource for policy makers. PMID- 21033648 TI - The relation between orthography and phonology from different angles: insights from psycholinguistics and second language acquisition. PMID- 21033649 TI - Strategic deployment of orthographic knowledge in phoneme detection. AB - The phoneme detection task is widely used in spoken-word recognition research. Alphabetically literate participants, however, are more used to explicit representations of letters than of phonemes. The present study explored whether phoneme detection is sensitive to how target phonemes are, or may be, orthographically realized. Listeners detected the target sounds [b, m, t, f, s, k] in word-initial position in sequences of isolated English words. Response times were faster to the targets [b, m, t], which have consistent word-initial spelling, than to the targets [f, s, k], which are inconsistently spelled, but only when spelling was rendered salient by the presence in the experiment of many irregularly spelled filler words. Within the inconsistent targets [f, s, k], there was no significant difference between responses to targets in words with more usual (foam, seed, cattle) versus less usual (phone, cede, kettle) spellings. Phoneme detection is thus not necessarily sensitive to orthographic effects; knowledge of spelling stored in the lexical representations of words does not automatically become available as word candidates are activated. However, salient orthographic manipulations in experimental input can induce such sensitivity. We attribute this to listeners' experience of the value of spelling in everyday situations that encourage phonemic decisions (such as learning new names). PMID- 21033650 TI - Auditory word serial recall benefits from orthographic dissimilarity. AB - The influence of orthographic knowledge has been consistently observed in dissimilarity speech recognition and metaphonological tasks. The present study provides data suggesting that such influence also pervades other cognitive domains phonological related to language abilities, such as verbal working memory. Using serial similarity effect recall of auditory seven-word lists, we observed that inter-item orthographic dissimilarity assists verbal working memory by reducing or even avoiding verbal serial recall the detrimental effect of phonological similarity. However, this orthographic modulation of the phonological similarity effect only occurred at positions four to six of the word list. Performance at position seven benefited from a recency effect that may be assumed to result from a more surface-level (acoustic-phonetic) representation, while better performance at positions one to three is attributable to primacy effects, and can be accounted for in terms of consolidation through recapitulation. The beneficial influence of orthographic knowledge may, therefore, only be apparent when the item stored in short-term memory takes the form of an abstract but unconsolidated phonological representation. PMID- 21033651 TI - The effect of L1 orthography on non-native vowel perception. AB - Previous research has shown that orthography influences the learning and processing of spoken non-native words. In this paper, we examine the effect of L1 orthography on non-native sound perception. In Experiment 1, 204 Spanish learners of Dutch and a control group of 20 native speakers of Dutch were asked to classify Dutch vowel tokens by choosing from auditorily presented options, in one task, and from the orthographic representations of Dutch vowels, in a second task. The results show that vowel categorization varied across tasks: the most difficult vowels in the purely auditory task were the easiest in the orthographic task and, conversely, vowels with a relatively high success rate in the purely auditory task were poorly classified in the orthographic task. The results of Experiment 2 with 22 monolingual Peruvian Spanish listeners replicated the main results of Experiment 1 and confirmed the existence of orthographic effects. Together, the two experiments show that when listening to auditory stimuli only, native speakers of Spanish have great difficulty classifying certain Dutch vowels, regardless of the amount of experience they may have with the Dutch language. Importantly, the pairing of auditory stimuli with orthographic labels can help or hinder Spanish listeners' sound categorization, depending on the specific sound contrast. PMID- 21033652 TI - Learning the phonological forms of new words: effects of orthographic and auditory input. AB - We investigated the relationship between the phonological and orthographic representations of new words for adult learners. Three groups of native English speakers learned a set of auditorily-presented pseudowords along with pictures indicating their "meanings". They were later tested on their memory of the words via an auditory word-picture matching test. While all three groups of participants heard the same auditory stimuli and saw the same pictures, the groups differed with respect to the written stimuli that accompanied each item during training. Some participants were presented with written forms for the auditory labels that were consistent with English spelling conventions (e.g., spelled form , auditory form [kamed]), while others saw written forms that were not consistent with English spelling conventions (e.g., spelled form , auditory form [kamed]), and a third group of participants was presented with no written forms. Participants who saw written forms that were not consistent with English spelling conventions showed interference from the words' spelled forms at test. This finding provides evidence for a relationship between orthographic and phonological representations for newly-learned words. PMID- 21033654 TI - Homophone dominance at the whole-word and sub-word levels: spelling errors suggest full-form storage of regularly inflected verb forms. AB - Two experiments and two corpus studies focus on homophone dominance in the spelling of regularly inflected verb forms, the phenomenon that the higher frequency homophone causes more intrusion errors on the lower-frequency one than vice versa. Experiment 1 was a speeded dictation task focusing on the Dutch imperative, a verb form whose formation rule is poorly known. A clear-cut effect of homophone dominance was found. This effect was equally strong when the target imperative was preceded by another imperative in the same sentence whose pronunciation reflected the spelling rule. Experiment 2 indicated that the effect of homophone dominance cannot be reduced to an effect of recency. Language users cannot discriminate a recently seen verb form when shown the two homophones. Instead, they choose the most frequent spelling pattern. In Corpus Study 1 a Google search on the world wide web revealed a sublexical effect of homophone dominance in the spelling errors on regular past tense forms. Corpus Study 2 demonstrated the validity of the search method. The sublexical effect of homophone dominance, involving units that cut across the stem-suffix boundary, lends itself naturally to a representational model of the connectionist or analogical processing tradition but is hard to reconcile with a rule-based account. PMID- 21033653 TI - Is a FAN always FUN? Phonological and orthographic effects in bilingual visual word recognition. AB - A visual semantic categorization task in English was performed by native English speakers (Experiment 1) and late bilinguals whose first language was Japanese (Experiment 2) or Spanish (Experiment 3). In the critical conditions, the target word was a homophone of a correct category exemplar (e.g., A BODY OF WATER--SEE; cf. SEA) or a word that differed from the correct exemplar by a phonological contrast absent in the bilinguals' first language (e.g., USED FOR COOLING DOWN- FUN; cf. FAN). Homophones elicited more false positive errors and slower processing than spelling controls in all groups. The Japanese-English bilinguals, but not the Spanish-English bilinguals, also displayed 'near-homophone' effects (i.e., homophone-like effects from minimal pairs on nonnative contrasts). We conclude that second-language visual word recognition is influenced by first language phonology, although the effect is conditioned by the first-language orthographic system. Near-homophone effects can occur when the orthographic systems of the late bilingual's two languages are different in type (e.g., alphabetic vs. non-alphabetic), but may be blocked if the languages use the same writing script (e.g., Roman alphabet). PMID- 21033655 TI - Targeting l1 cell adhesion molecule using lentivirus-mediated short hairpin RNA interference reverses aggressiveness of oral squamous cell carcinoma. AB - The L1 cell adhesion molecule (L1CAM) has been implicated in tumor progression of many types of cancers, but its role in oral squamous cell carcinoma (OSCC) has not been investigated. In the present study, we demonstrated overexpression of L1CAM in OSCC cells, but not in normal keratinocytes, using both clinical specimens and cell lines. This overexpression demonstrated a strong correlation with less differentiation and a higher invasion potential of cancer cells, supporting the significance of L1CAM in human OSCC tumor progression. Targeting L1CAM gene expression in SCC4 cells overexpressing L1CAM using a lentivirus mediated small hairpin RNA (shRNA) led to a significant reduction in cell proliferation in vitro via retardation of cell cycle at the G1 phase. In addition, shRNA knockdown of L1CAM strongly attenuated the migration and invasion of SCC4 cells, and this was also observed to parallel increased E-cadherin levels and decreased levels of vimentin, fibronectin, and Snail-family transcription factors, indicating that L1CAM expression was related to the epithelial mesenchymal transition. Furthermore, while mice receiving orthotopically placed control SCC4 cells died within 40 days due to invasive tumor growth and regional lymph node metastasis, prolonged animal survival and complete suppression of tumor progression was observed in mice implanted with L1CAM-deficent SCC4 cells, further substantiating the fundamental importance of L1CAM in OSCC pathophysiology. Our findings suggested that L1CAM is a critical mediator of tumor progression in OSCC, and targeting L1CAM using lentivirus-mediated shRNA may be a useful molecular pharmaceutical approach for the treatment of advanced OSCC. PMID- 21033656 TI - Applicability domains for classification problems: Benchmarking of distance to models for Ames mutagenicity set. AB - The estimation of accuracy and applicability of QSAR and QSPR models for biological and physicochemical properties represents a critical problem. The developed parameter of "distance to model" (DM) is defined as a metric of similarity between the training and test set compounds that have been subjected to QSAR/QSPR modeling. In our previous work, we demonstrated the utility and optimal performance of DM metrics that have been based on the standard deviation within an ensemble of QSAR models. The current study applies such analysis to 30 QSAR models for the Ames mutagenicity data set that were previously reported within the 2009 QSAR challenge. We demonstrate that the DMs based on an ensemble (consensus) model provide systematically better performance than other DMs. The presented approach identifies 30-60% of compounds having an accuracy of prediction similar to the interlaboratory accuracy of the Ames test, which is estimated to be 90%. Thus, the in silico predictions can be used to halve the cost of experimental measurements by providing a similar prediction accuracy. The developed model has been made publicly available at http://ochem.eu/models/1 . PMID- 21033657 TI - Effect of enzymatic hydrolysis on native starch granule structure. AB - Enzymatic digestion of six starches of different botanical origin was studied in real time by in situ time-resolved small-angle neutron scattering (SANS) and complemented by the analysis of native and digested material by X-ray diffraction, differential scanning calorimetry, small-angle X-ray scattering, and scanning electron microscopy with the aim of following changes in starch granule nanostructure during enzymatic digestion. This range of techniques enables coverage over five orders of length-scale, as is necessary for this hierarchically structured material. Starches studied varied in their digestibility and displayed structural differences in the course of enzymatic digestion. The use of time-resolved SANS showed that solvent-drying of digested residues does not induce any structural artifacts on the length scale followed by small-angle scattering. In the course of digestion, the lamellar peak intensity gradually decreased and low-q scattering increased. These trends were more substantial for A-type than for B-type starches. These observations were explained by preferential digestion of the amorphous growth rings. Hydrolysis of the semicrystalline growth rings was explained on the basis of a liquid crystalline model for starch considering differences between A-type and B-type starches in the length and rigidity of amylopectin spacers and branches. As evidenced by differing morphologies of enzymatic attack among varieties, the existence of granular pores and channels and physical penetrability of the amorphous growth ring affect the accessibility of the enzyme to the substrate. The combined effects of the granule microstructure and the nanostructure of the growth rings influence the opportunity of the enzyme to access its substrate; as a consequence, these structures determine the enzymatic digestibility of granular starches more than the absolute physical densities of the amorphous growth rings and amorphous and crystalline regions of the semicrystalline growth rings. PMID- 21033658 TI - Effectiveness of UV-C equipped vacuum at reducing culturable surface-bound microorganisms on carpets. AB - Carpets are both sinks and sources for exposure to chemicals, allergens, and microbes and consequently influence health, including asthma, allergies, and infectious diseases. Asthmatics, children, and the immune-compromised are particularly vulnerable to health risks resulting from exposure to carpet contaminants. To address this risk, a commercial upright vacuum cleaner with an ultraviolet germicidal lamp (lambda=253.7 nm, UVC) has been developed for residential and commercial uses. However, its effectiveness in reducing microbial load on real-world carpets has not been previously demonstrated. Accordingly, the purpose of the current study was to evaluate the effectiveness of a UVC-equipped vacuum in reducing the carpet surface-bound microbial load. This was accomplished by comparing the carpet microbial surface load from pre- to post-treatment of 9 ft(2) in-use carpet sections under three treatment scenarios: 1) UVC alone (UV), 2) the beater-bar plus vacuum (BB+Vac), or 3) a combination of all three (COMB). Each treatment was two minutes in duration. Microbial surface loads were measured by pressing contact plates containing Sabourauds Dextrose agar onto the carpet surface. In-use carpets from three locations were tested in place. The treatment effect was evaluated at two levels. First, we considered the mean reduction in CFU from pre- to post-treatment for each 9 ft(2) carpet grid (n = 4 for each treatment). The second level considered each 1 ft(2) section using a paired analysis (n = 40 to 49 for each treatment). A total of 125 pre/post-sample pairs were collected across the three treatments. Results showed that all three treatments were associated with a reduction in carpet microbial load (p < 0.0001). The COMB yielded the largest reduction of 13 CFU/plate (87% reduction) and was approximately the sum of the individual effects of either UVC (6.6 CFU/plate, 60% reduction, p = 0.009) or BB+Vac (7.3 CFU/plate, 78% reduction, p < 0.0001). We therefore conclude that a UVC-equipped vacuum approximately doubles the unit's effectiveness in reducing surface-bound microbial load, thereby holding promise as a means for decreasing indoor infectious disease risk. PMID- 21033659 TI - A quantitative PCR assay for aerobic, vinyl chloride- and ethene-assimilating microorganisms in groundwater. AB - Vinyl chloride (VC) is a known human carcinogen that is primarily formed in groundwater via incomplete anaerobic dechlorination of chloroethenes. Aerobic, ethene-degrading bacteria (etheneotrophs), which are capable of both fortuitous and growth-linked VC oxidation, could be important in natural attenuation of VC plumes that escape anaerobic treatment. In this work, we developed a quantitative, real-time PCR (qPCR) assay for etheneotrophs in groundwater. We designed and tested degenerate qPCR primers for two functional genes involved in aerobic, growth-coupled VC- and ethene-oxidation (etnC and etnE). Primer specificity to these target genes was tested by comparison to nucleotide sequence databases, PCR analysis of template DNA extracted from isolates and environmental samples, and sequencing of qPCR products obtained from VC-contaminated groundwater. The assay was made quantitative by constructing standard curves (threshold cycle vs log gene copy number) with DNA amplified from Mycobacterium strain JS60, an etheneotrophic isolate. Analysis of groundwater samples from three different VC-contaminated sites revealed that etnC abundance ranged from 1.6 * 10(3) - 1.0 * 10(5) copies/L groundwater while etnE abundance ranged from 4.3 * 10(3) - 6.3 * 10(5) copies/L groundwater. Our data suggest this novel environmental measurement method will be useful for supporting VC bioremediation strategies, assisting in site closure, and conducting microbial ecology studies involving etheneotrophs. PMID- 21033660 TI - Isotopic tracking of Hanford 300 area derived uranium in the Columbia River. AB - Our objectives in this study are to quantify the discharge rate of uranium (U) to the Columbia River from the Hanford Site's 300 Area and to follow that U downriver to constrain its fate. Uranium from the Hanford Site has variable isotopic composition due to nuclear industrial processes carried out at the site. This characteristic makes it possible to use high-precision isotopic measurements of U in environmental samples to identify even trace levels of contaminant U, determine its sources, and estimate discharge rates. Our data on river water samples indicate that as much as 3.2 kg/day can enter the Columbia River from the 300 Area, which is only a small fraction of the total load of dissolved natural background U carried by the Columbia River. This very low level of Hanford derived U can be discerned, despite dilution to <1% of natural background U, 400 km downstream from the Hanford Site. These results indicate that isotopic methods can allow the amounts of U from the 300 Area of the Hanford Site entering the Columbia River to be measured accurately to ascertain whether they are an environmental concern or insignificant relative to natural uranium background in the Columbia River. PMID- 21033661 TI - What determines the inhibition effectiveness of ATA, BTAH, and BTAOH corrosion inhibitors on copper? AB - Three corrosion inhibitors for copper-3-amino-1,2,4-triazole (ATA), benzotriazole (BTAH), and 1-hydroxybenzotriazole (BTAOH)-were investigated by corrosion experiments and atomistic computer simulations. The trend of corrosion inhibition effectiveness of the three inhibitors on copper in near-neutral chloride solution is determined experimentally as BTAH ? ATA ? BTAOH. A careful analysis of the results of computer simulations based on density functional theory allowed to pinpoint the superior inhibiting action of BTAH and ATA as a result of their ability to form strong N-Cu chemical bonds in deprotonated form. While these bonds are not as strong as the Cl-Cu bonds, the presence of solvent favors the adsorption of inhibitor molecules onto the surface due to stronger solvation of the Cl(-) anions. Moreover, benzotriazole displays the largest affinity among the three inhibitors to form intermolecular aggregates, such as [BTA-Cu](n) polymeric complex. This is another factor contributing to the stability of the protective inhibitor film on the surface, thus making benzotriazole an outstanding corrosion inhibitor for copper. These findings cannot be anticipated on the basis of inhibitors' molecular electronic properties alone, thus emphasizing the importance of a rigorous modeling of the interactions between the components of the corrosion system in corrosion inhibition studies. PMID- 21033663 TI - Synthesis and photophysical studies of chiral helical macrocyclic scaffolds via coordination-driven self-assembly of 1,8,9,16-tetraethynyltetraphenylene. formation of monometallic platinum(II) and dimetallic platinum(II)-ruthenium(II) complexes. AB - This paper is concerned with the synthesis and reactions of enantiopure 1,8,9,16 tetraethynyltetraphenylene (3). We obtained 3 in 34% yield through four steps starting from 1,8,9,16-tetrahydroxytetraphenylene (2a) via a functional group interconversion strategy. On the basis of this chiral "helical" building block, three rigid helical macrocycles 14, 15, and 22 were designed. Complexes 14 and 15 were constructed via coordination-driven self-assembly with platinum(II) complexes 8 and 9b, while 22 cannot be obtained successfully. Then macrocycle 28 was designed on the structural basis of 22 to which octyl chains were introduced, in the hope of improving the solubility of the complex. Macrocycle 28 was finally formed and was characterized by NMR spectroscopy, elemental analysis, and electrospray mass spectrometry. For the enantiopure 15 and 28, circular dichroism (CD) spectra also exhibited chiral properties. Complexes 27 and 28 both exhibited an intense emission band at 621 nm in acetonitrile at 298 K upon excitation at lambda > 420 nm. PMID- 21033662 TI - Comparison of leaf and fruit metabolism in two tomato (Solanum lycopersicum L.) genotypes varying in total soluble solids. AB - Sink and source activity in two tomato (Solanum lycopersicum L.) genotypes that vary in fruit Brix were investigated to identify differences that potentially underscore this trait. Solara (Brix 9%) accumulated almost twice the glucose, fructose, and sucrose in ripe fruit and had a higher horticultural yield (25% greater) compared to Moneymaker (Brix 5%). 14C-glucose feeding suggested large disparities in sucrose metabolism in ripe fruit between genotypes. Biochemical pathways in the leaf adjacent to a fruiting truss at night were also analyzed since in many species, this is the period when leaf reserves are mobilized to feed the plant. Surprisingly, leaf metabolism, i.e., starch and sugar content, the levels of polar metabolites assayed by GC-TOF MS and 14CO2-pulse-chase fluxes in detached leaves, did not change between the day and night in either genotype. Solara has a higher morphological source-to-sink ratio, and this may contribute to higher Brix in that genotype. PMID- 21033664 TI - Enantioselective copper-catalyzed intramolecular O-H insertion: an efficient approach to chiral 2-carboxy cyclic ethers. AB - A copper-catalyzed asymmetric intramolecular O-H insertion of omega-hydroxy-alpha diazoesters has been accomplished by using chiral spiro bisoxazoline ligands. This highly enantioselective intramolecular O-H insertion reaction provides an efficient approach to a variety of synthetically important chiral 2-carboxy cyclic ethers with different ring sizes as well as substitution patterns. PMID- 21033666 TI - Synthesis of defined ubiquitin dimers. AB - Many proteins are post-translationally modified by the attachment of poly ubiquitin (Ub) chains. Notably, the biological function of the attached Ub chain depends on the specific lysine residue used for conjugate formation. Here, we report an easy and efficient method to synthesize site-specifically linked Ub dimers by click reaction between two artificial amino acids. In fact, we were able to synthesize all seven naturally occurring Ub connectivities, providing the first example of a method that gives access to all Ub dimers. Furthermore, these synthetic Ub dimers are recognized by the natural ubiquitination machinery and are proteolytically stable, making them optimal candidates to further investigate the function of differently linked Ub chains. PMID- 21033665 TI - Dual mechanisms of HNO generation by a nitroxyl prodrug of the diazeniumdiolate (NONOate) class. AB - Here we describe a novel caged form of the highly reactive bioeffector molecule, nitroxyl (HNO). Reacting the labile nitric oxide (NO)- and HNO-generating salt of structure iPrHN-N(O)?NO(-)Na(+) (1, IPA/NO) with BrCH(2)OAc produced a stable derivative of structure iPrHN-N(O)?NO-CH(2)OAc (2, AcOM-IPA/NO), which hydrolyzed an order of magnitude more slowly than 1 at pH 7.4 and 37 degrees C. Hydrolysis of 2 to generate HNO proceeded by at least two mechanisms. In the presence of esterase, straightforward dissociation to acetate, formaldehyde, and 1 was the dominant path. In the absence of enzyme, free 1 was not observed as an intermediate and the ratio of NO to HNO among the products approached zero. To account for this surprising result, we propose a mechanism in which base-induced removal of the N-H proton of 2 leads to acetyl group migration from oxygen to the neighboring nitrogen, followed by cleavage of the resulting rearrangement product to isopropanediazoate ion and the known HNO precursor, CH(3)-C(O)-NO. The trappable yield of HNO from 2 was significantly enhanced over 1 at physiological pH, in part because the slower rate of hydrolysis for 2 generated a correspondingly lower steady-state concentration of HNO, thus, minimizing self consumption and enhancing trapping by biological targets such as metmyoglobin and glutathione. Consistent with the chemical trapping efficiency data, micromolar concentrations of prodrug 2 displayed significantly more potent sarcomere shortening effects relative to 1 on ventricular myocytes isolated from wild-type mouse hearts, suggesting that 2 may be a promising lead compound for the development of heart failure therapies. PMID- 21033667 TI - Cobalt-mediated, enantioselective synthesis of C(2) and C(1) dienes. AB - The asymmetric C-H functionalization of norbornene and norbornadiene with five-, six-, and seven-membered cyclic enones mediated by the reactive intermediate [{eta(5)-((t)BuMe(2)Si)C(5)H(4)}Co(NO)(2)] is reported. A novel base mixture derived from enantiopure ammonium salts and NaHMDS was used as a source of chirality, and this enantioselective desymmetrization of C(s) alkenes has been applied to the asymmetric synthesis of C(2)- and C(1)-symmetric diene ligands in high regioselectivity (3.7-20:1 anti/syn), near perfect diastereoselectivity (>99:1 dr), and high enantioselectivity (90-96% ee). PMID- 21033668 TI - Antioxidant activity of glyceollins derived from soybean elicited with Aspergillus sojae. AB - The extract of soybean exposed to biotic elicitors such as food-grade fungus is known to have antioxidant activity. Glyceollins were major bioactive compounds present in soybean elicited by fungi and shown to have antifungal and anticancer activities. The purpose of present study was to evaluate the antioxidant activities of glyceollins by measuring ferric reducing antioxidant power (FRAP), 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, singlet oxygen quenching, 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging, hydroxyl radical scavenging activity, and lipid peroxidation inhibition. In addition, the antioxidant potential of glyceollins were measured by a fluorescent probe, 2',7'-dichlorofluorescin diacetate (DCFDA), and dihydroethidium (DHE) in mouse hepatoma hepa1c1c7 cells in which they were insulted with H2O2 to generate reactive oxygen species (ROS). Glyceollins showed a strong reducing power and inhibited lipid peroxidation, with significant scavenging activities of radicals including singlet oxygen, superoxide anion, ABTS, and DPPH. We also found that glyceollins significantly suppressed H2O2 induced ROS production in hepa1c1c7 cells. Therefore, glyceollins deserve further study as natural antioxidants and nutraceuticals. PMID- 21033669 TI - Synthesis and biological evaluation of Apogossypolone derivatives as pan-active inhibitors of antiapoptotic B-cell lymphoma/leukemia-2 (Bcl-2) family proteins. AB - Overexpression of antiapoptotic Bcl-2 family proteins is commonly related with tumor maintenance, progression, and chemoresistance. Inhibition of these antiapoptotic proteins is an attractive approach for cancer therapy. Guided by nuclear magnetic resonance (NMR) binding assays, a series of 5,5' substituted compound 6a (Apogossypolone) derivatives was synthesized and identified pan active antagonists of antiapoptotic Bcl-2 family proteins, with binding potency in the low micromolar to nanomolar range. Compound 6f inhibits the binding of BH3 peptides to Bcl-X(L), Bcl-2, and Mcl-1 with IC(50) values of 3.10, 3.12, and 2.05 MUM, respectively. In a cellular assay, 6f potently inhibits cell growth in several human cancer cell lines in a dose-dependent manner. Compound 6f further displays in vivo efficacy in transgenic mice and demonstrated superior single agent antitumor efficacy in a PPC-1 mouse xenograft model. Together with its negligible toxicity, compound 6f represents a promising drug lead for the development of novel apoptosis-based therapies for cancer. PMID- 21033670 TI - Design, synthesis, and DNA-binding of N-alkyl(anilino)quinazoline derivatives. AB - New N-alkylanilinoquinazoline derivatives 5, 12, 20, and 22 have been prepared from 4-chloro-6,7-dimethoxyquinazoline 3, 4-chloro-6,7-methylenedioxyquinazoline 19, and commercially available anilines. Differents classes of compounds substituted by an aryloxygroup (6a-c, 16a,b, and 17a,b), (aminophenyl)ureas (12a,b and 13a-f), anilines (4a-m, 20a,b), N-alkyl(aniline) (5a-m, 21a,b, 22a,d), and N-aminoalkyl(aniline) (22e-g) have been synthesized. These molecules were evaluated for their cytotoxic activities and as potential DNA intercalating agents. We studied the strength and mode of binding to DNA of these molecules by DNA melting temperature measurements, fluorescence emission, and circular dichroism. The results of various spectral and gel electrophoresis techniques obtained with the different compounds, in particular compounds 5g and 22f, revealed significant DNA interaction. These experiments confirm that the N aminoalkyl(anilino)-6,7-dimethoxyquinazoline nucleus is an efficient pharmacophore to trigger binding to DNA, via an intercalative binding process. PMID- 21033671 TI - 2'-Deoxy-2'-spirocyclopropylcytidine revisited: a new and selective inhibitor of the hepatitis C virus NS5B polymerase. AB - The current therapy for hepatitis C virus (HCV) infection has limited efficacy, in particular against the genotype 1 virus, and a range of side effects. In this context of high unmet medical need, more efficacious drugs targeting HCV nonstructural proteins are of interest. Here we describe 2'-deoxy-2' spirocyclopropylcytidine (5) as a new inhibitor of the HCV NS5B RNA-dependent RNA polymerase, displaying an EC(50) of 7.3 MUM measured in the Huh7-Rep cell line and no associated cytotoxicity (CC(50) > 98.4 MUM). Computational results indicated high similarity between 5 and related HCV inhibiting nucleosides. A convenient synthesis was devised, facilitating synthesis of multigram quantities of 5. As the exposure measured after oral administration of 5 was found to be limited, the 3'-mono- and 3',5'-diisobutyryl ester prodrugs 20 and 23, respectively, were evaluated. The oral dosing of 23 led to substantially increased exposure to 5 in both rats and dogs. PMID- 21033672 TI - Dielectric coagulometry: a new approach to estimate venous thrombosis risk. AB - We present dielectric coagulometry as a new technique to estimate the risk of venous thrombosis by measuring the permittivity change associated with the blood coagulation process. The method was first tested for a simple system of animal erythrocytes suspended in fibrinogen solution, where the coagulation rate was controlled by changing the amount of thrombin added to the suspension. Second, the method was applied to a more realistic system of human whole blood, and the inherent coagulation process was monitored without artificial acceleration by a coagulation initiator. The time dependence of the permittivity at a frequency around 1 MHz showed a distinct peak at a time that corresponds to the clotting time. Our theoretical modeling revealed that the evolution of heterogeneity and the sedimentation in the system cause the peak of the permittivity. PMID- 21033673 TI - Chemometric strategy for modeling metabolic biological space along the gastrointestinal tract and assessing microbial influences. AB - Over the past decade, the analysis of metabolic data with advanced chemometric techniques has offered the potential to explore functional relationships among biological compartments in relation to the structure and function of the intestine. However, the employed methodologies, generally based on regression modeling techniques, have given emphasis to region-specific metabolic patterns, while providing only limited insights into the spatiotemporal metabolic features of the complex gastrointestinal system. Hence, novel approaches are needed to analyze metabolic data to reconstruct the metabolic biological space associated with the evolving structures and functions of an organ such as the gastrointestinal tract. Here, we report the application of multivariate curve resolution (MCR) methodology to model metabolic relationships along the gastrointestinal compartments in relation to its structure and function using data from our previous metabonomic analysis. The method simultaneously summarizes metabolite occurrence and contribution to continuous metabolic signatures of the different biological compartments of the gut tract. This methodology sheds new light onto the complex web of metabolic interactions with gut symbionts that modulate host cell metabolism in surrounding gut tissues. In the future, such an approach will be key to provide new insights into the dynamic onset of metabolic deregulations involved in region-specific gastrointestinal disorders, such as Crohn's disease or ulcerative colitis. PMID- 21033674 TI - Evaluation of data analysis strategies for improved mass spectrometry-based phosphoproteomics. AB - Here we describe a set of enhanced data processing and filtering methods to improve significance and coverage of phosphopeptide identifications by mass spectrometry. We demonstrate that for samples of limited complexity, spectra based estimation of false discovery rates will lead to overprediction of confidently identified phosphorylated peptides due to a bias caused by multiple fragmentation of highly abundant peptide species. We further provide evidence that fragmentation of abundant peptides at the tails of their chromatographic peaks is a major source for false positive peptide matches and that overall confidence in phosphopeptide identifications can be improved by a chromatographic peak-based aggregation scheme, intensity rank-based neutral loss and optimized mass error filters. When replicate runs of a standard sample were performed using different fragmentation techniques on an Orbitrap mass spectrometer we observed improvements of 7-31% in phosphopeptide coverage depending on the fragmentation method and the desired false discovery rate. PMID- 21033675 TI - Localized nanoscopic surface measurements of nickel-modified mica for single molecule DNA sequence sampling. AB - Cleaved, cation-derivatized Muscovite mica is utilized extensively in atomic force microscopy (AFM) imaging because of its flatness over large areas (millimeter cleavage planes with local root-mean-square roughness < 0.3 nm), ease of preparation, and ability to adsorb charged biomolecules such as DNA (work by Hansma and Laney, Guthold et al., and McMaster et al.). In particular, NiCl(2) treatment has become a common method for controlling DNA adsorption on mica substrates while retaining the mica's ultraflat surface (work by Pietrement et al.). While several studies have modeled the mica/metal ion/DNA system using macroscopic colloidal theory (DLVO, etc.; Pietrement et al., Sushko et al., Pastre et al., and Cheng et al.), nickel/mica's physicochemical properties have not been well characterized on the nanoscale. Efforts to manipulate and engineer DNA nanostructures would benefit greatly from a better understanding of the surface chemistry of nickel/mica. Here we present in situ nanometer- and attogram scale measurements and thermodynamic simulation results that show that the surface chemistry of nickel-treated mica is more complex than generally appreciated by AFM practitioners because of metal-ion speciation effects present at neutral pH. We also show that, under certain preparations, nickel/mica allows in situ nanoscopic nucleotide sequence mapping within individual surface-adsorbed DNA molecules by permitting localized, controlled desorption of the double helix by soluble DNA binding enzymes. These results should aid efforts to precisely control the DNA/mica binding affinity, particularly at the physiological pH ranges required by enzymatic biochemistry (pH 7.0-8.5), and facilitate the development of more complex and useful biochemical manipulations of adsorbed DNA, such as single-molecule sequencing. PMID- 21033676 TI - Multiplexed bead-based mesofluidic system for gene diagnosis and genotyping. AB - We have developed a novel multiplexed bead-based mesofluidic system (MBMS) based on the specific recognition events on the surface of a series of microbeads (diameter 250 MUm) arranged in polydimethylsiloxane (PDMS) microchannels (diameter 300 MUm) with the predetermined order and assembled an apparatus implementing automatically the high-throughput bead-based assay and further demonstrated its feasibility and flexibility of gene diagnosis and genotyping, such as beta-thalassemia mutation detection and HLA-DQA genotyping. The apparatus, consisting of bead-based mesofluidic PDMS chip, liquid-processing module, and fluorescence detection module, can integrate the procedure of automated-sampling, hybridization reactions, washing, and in situ fluorescence detection. The results revealed that MBMS is fast, has high sensitivity, and can be automated to carry out parallel and multiplexed genotyping and has the potential to open up new routes to flexible, high-throughput approaches for bioanalysis. PMID- 21033677 TI - Comparative analysis of QSAR models for predicting pK(a) of organic oxygen acids and nitrogen bases from molecular structure. AB - For 1143 organic compounds comprising 580 oxygen acids and 563 nitrogen bases that cover more than 17 orders of experimental pK(a) (from -5.00 to 12.23), the pK(a) prediction performances of ACD, SPARC, and two calibrations of a semiempirical quantum chemical (QC) AM1 approach have been analyzed. The overall root-mean-square errors (rms) for the acids are 0.41, 0.58 (0.42 without ortho substituted phenols with intramolecular H-bonding), and 0.55 and for the bases are 0.65, 0.70, 1.17, and 1.27 for ACD, SPARC, and both QC methods, respectively. Method-specific performances are discussed in detail for six acid subsets (phenols and aromatic and aliphatic carboxylic acids with different substitution patterns) and nine base subsets (anilines, primary, secondary and tertiary amines, meta/para-substituted and ortho-substituted pyridines, pyrimidines, imidazoles, and quinolines). The results demonstrate an overall better performance for acids than for bases but also a substantial variation across subsets. For the overall best-performing ACD, rms ranges from 0.12 to 1.11 and 0.40 to 1.21 pK(a) units for the acid and base subsets, respectively. With regard to the squared correlation coefficient r2, the results are 0.86 to 0.96 (acids) and 0.79 to 0.95 (bases) for ACD, 0.77 to 0.95 (acids) and 0.85 to 0.97 (bases) for SPARC, and 0.64 to 0.87 (acids) and 0.43 to 0.83 (bases) for the QC methods, respectively. Attention is paid to structural and method-specific causes for observed pitfalls. The significant subset dependence of the prediction performances suggests a consensus modeling approach. PMID- 21033678 TI - Sr(3)Co(2)O(4.33)h(0.84): an extended transition metal oxide-hydride. AB - Reaction of the n = 2 Ruddlesden-Popper oxide Sr(3)Co(2)O(5.80) with CaH(2) yields an extended oxide-hydride phase: Sr(3)Co(2)O(4.33)H(0.84). Neutron powder diffraction data reveal the material adopts a body-centered orthorhombic structure (Immm: a = 3.7551(5) A, b = 3.7048(4) A, c = 21.480(3) A) in which the hydride ions are accommodated within disordered CoO(1.16)H(0.46) layers. Low temperature neutron powder diffraction data show no evidence for long-range magnetic order, suggesting the chemical disorder in the anion lattice of the material leads to magnetic frustration. PMID- 21033679 TI - Electron density guided fragment-based lead discovery of ketohexokinase inhibitors. AB - A fragment-based drug design paradigm has been successfully applied in the discovery of lead series of ketohexokinase inhibitors. The paradigm consists of three iterations of design, synthesis, and X-ray crystallographic screening to progress low molecular weight fragments to leadlike compounds. Applying electron density of fragments within the protein binding site as defined by X-ray crystallography, one can generate target specific leads without the use of affinity data. Our approach contrasts with most fragment-based drug design methodology where solution activity is a main design guide. Herein we describe the discovery of submicromolar ketohexokinase inhibitors with promising druglike properties. PMID- 21033680 TI - Stereospecific halogenation of P(O)-H bonds with copper(II) chloride affording optically active Z1Z2P(O)Cl. AB - A general and efficient method for the preparation of optically active Z1Z2P(O)Cl from the easily prepared optically active H-phosphinates and H-phosphine oxides was reported. H-Phosphinates and H-phosphine oxides react stereospecifically with CuCl2 to produce the corresponding optically active Z1Z2P(O)Cl with retention of configuration at the phosphorus center. Optically active Z1Z2P(O)Cl reacts easily with a variety of nucleophiles to produce other chiral organophosphorus acid derivatives with inversion of configuration at phosphorus. PMID- 21033681 TI - A density-functional study of heterometallic Cr-based molecular rings. AB - We present a density-functional theoretical investigation of the electronic and magnetic properties of octametallic Cr-based molecular antiferromagnetic rings. The presence of the divalent magnetic ion M unbalances the charge and the spin of the parent Cr(8) ring, leading to a finite total spin in the molecules. Results are presented for Cr(8), i.e., [Cr(8)F(8)(O(2)CH)(16)] (1), and for Cr(7)M rings belonging to two different derivatives, i.e., [Me(2)NH(2)][Cr(7)MF(8)(O(2)CH)(16)], with M = Ni, Mn, Fe, and Cu, and Me=CH(3) (2, "green" derivative), and [Cr(7) NiF(3)(C(6)H(10)NO(5))(O(2)CH)(15) (H(2)O)] (3, "purple" derivative). Exchange interaction parameters have been extracted from broken-symmetry calculations and compared with the available experiments; in agreement with them, we find that exchange parameters are rather similar in the two derivatives, although somewhat larger in the "purple" derivative. The analysis of the electronic properties shows some differences depending on M, in particular in the size of the highest occupied molecular orbital to lowest unoccupied molecular orbital (HOMO-LUMO) gaps. For all the "green" rings we observe that the HOMOs are localized on the divalent ion site, while the HOMOs for the "purple" Cr(7)Ni have a more delocalized nature; LUMOs, instead, are, except for "green" Cr(7)Cu, localized on the Cr atoms opposite to the M site. We discuss how these findings may show up in terms of an asymmetric I-V curve in molecular junctions working in the sequential tunneling regime, or help in discerning the orientation of the molecules with respect to a surface, in scanning tunneling experiments. PMID- 21033682 TI - Mild and expedient asymmetric reductions of alpha,beta-unsaturated alkenyl and alkynyl ketones by TarB-NO2 and mechanistic investigations of ketone reduction. AB - A facile and mild reduction procedure is reported for the preparation of chiral allylic and propargyl alcohols in high enantiomeric purity. Under optimized conditions, alkynyl and alkenyl ketones were reduced by TarB-NO2 and NaBH4 at 25 degrees C in 1 h to produce chiral propargyl and allylic alcohols with enantiomeric excesses and yields up to 99%. In the case of alpha,beta-unsaturated alkenyl ketones, alpha-substituted cycloalkenones were reduced with up to 99% ee, while more substituted and acyclic derivatives exhibited lower induction. For alpha,beta-ynones, it was found that highly branched aliphatic ynones were reduced with optimal induction up to 90% ee, while reduction of aromatic and linear aliphatic derivatives resulted in more modest enantioselectivity. Using the (L)-TarB-NO2 reagent derived from (L)-tartaric acid, we routinely obtained highly enantioenriched chiral allylic and propargyl alcohols with (R) configuration. Since previous models and a reduction of a saturated analogue predicted propargyl products of (S) configuration, a series of new mechanistic studies were conducted to determine the likely orientation of aromatic, alkenyl, and alkynyl ketones in the transition state. PMID- 21033684 TI - Interaction of gums (guar, carboxymethylhydroxypropyl guar, diutan, and xanthan) with surfactants (DTAB, CTAB, and TX-100) in aqueous medium. AB - The interaction of surfactants dodecyltrimethylammonium bromide (DTAB), cetyltrimethylammonium bromide (CTAB), and p-tert-octylphenoxypolyoxyethylene (9.5) ether (TX-100) with guar (Gr), carboxymethylhydroxypropyl guar (CMHPG), diutan (Dn), and xanthan (Xn) gums has been studied employing conductometry, tensiometry, microcalorimetry, viscometry, and atomic force microscopy (AFM) techniques. Both weak and strong interactions were observed. CTAB interacted stronger than DTAB with the gums. The surfactant-gum interaction process was enhanced by the presence of borate ions in the solution; the borate ion itself also manifested interaction with the surfactants comparable with that of water soluble polymers polyvinyl alcohol, polyoxyethylene, and so forth. Viscometric results supported configurational changes of the gum molecules by interaction with surfactants. The geometry of the pure gums and their CTAB interacted products in the dried states was ascertained from AFM measurements; spherical and prolate shapes were observed for pure gums, and distorted states were observed for their surfactant complexed species. Detailed topological features of these entities were ascertained. PMID- 21033683 TI - Activating multistep charge-transfer processes in fullerene-subphthalocyanine ferrocene molecular hybrids as a function of pi-pi orbital overlap. AB - We have synthesized two different fullerene-subphthalocyanine-ferrocene conjugates. The molecules were designed so that the ferrocene unit is linked at the subphthalocyanine axial position through a phenoxy spacer while the C(60) is rigidly held close to the concave face of the macrocycle via a 3-fold C(3) symmetrical anchoring. The Bingel trisaddition reaction leading to the final products proceeded with very high regioselectivities and full diastereoselectivity. The only difference between both systems is the length of the triple tether employed, which finely regulates the regioselectivity of the trisaddition reaction and the distance between the subphthalocyanine and the C(60) complementary pi-pi surfaces. Thus, when the tether is connected to the subphthalocyanine through a direct C-C bond, a short pi-pi distance of 3.25-3.30 A was calculated. In contrast, when it is connected through a slightly longer C-O C bond, the distance increases to 3.5-3.6 A. This pi-pi distance has a strong influence on the ground-state electronic interactions between the subphthalocyanine and the C(60), as determined from electronic absorption and cyclic voltammetry measurements. In addition, fluorescence and time-resolved transient absorption experiments demonstrated that different mechanisms operate in the two systems after photoexcitation. Despite the similar HOMO-LUMO gaps, only when the two complementary pi-pi surfaces of the subphthalocyanine and the C(60) are held at a close distance, therefore showing a high degree of orbital overlap, is a multistep electron transfer process triggered, ultimately leading to the long-lived, spatially separated C(60) radical anion and ferrocenium radical cation pair. A full account of the synthesis, characterization, and studies of the ground- and excited-state electronic interactions occurring in these conjugates, as well as in their reference C(60)-subphthalocyanine and subphthalocyanine-ferrocene dyads, is presented in this article. PMID- 21033685 TI - A facile and stereocontrolled synthesis of gamma-substituted gamma fluoroglutamates by conjugate addition: conflicting effect between fluorinated enaminoester and hinderered Michael acceptor. AB - Asymmetric Michael addition of chiral 2-fluoroenaminoesters derived from (S)-1 phenylethylamine to alpha-substituted methyl acrylate leads to diastereomeric gamma-substituted gamma-fluoroglutamate precursors. The tertiary center bearing the amino acid function in its natural configuration is generated with a high level of stereocontrol in contrast to the quaternary carbon center. Diastereomeric gamma-substituted gamma-fluoroglutamates were efficiently separated and isolated as thioketal derivatives harboring very good enantioselectivity. The Michael addition diastereoselectivity was studied for the asymmetric conjugate addition of fluorinated chiral beta-enaminoester to methyl alpha-acetamidoacrylate by (19)F and (1)H NMR experiments as well as ab initio computations. An interfering conjunction between hindrance of the electrophile and a destabilizing effect of the fluorine atom borne by the nucleophile is revealed. PMID- 21033686 TI - Cu2Se nanoparticles with tunable electronic properties due to a controlled solid state phase transition driven by copper oxidation and cationic conduction. AB - Stoichiometric copper(I) selenide nanoparticles have been synthesized using the hot injection method. The effects of air exposure on the surface composition, crystal structure, and electronic properties were monitored using X-ray photoelectron spectroscopy, X-ray diffraction, and conductivity measurements. The current-voltage response changes from semiconducting to ohmic, and within a week a 3000-fold increase in conductivity is observed under ambient conditions. The enhanced electronic properties can be explained by the oxidation of Cu(+) and Se(2-) on the nanoparticle surface, ultimately leading to a solid-state conversion of the core from monoclinic Cu(2)Se to cubic Cu(1.8)Se. This behavior is a result of the facile solid-state ionic conductivity of cationic Cu within the crystal and the high susceptibility of the nanoparticle surface to oxidation. This regulated transformation is appealing as one could envision using layers of Cu(2)Se nanoparticles as both semiconducting and conducting domains in optoelectronic devices simply by tuning the electronic properties for each layer through controlled oxidation. PMID- 21033687 TI - Formation of nanometric HT-LiCoO(2) by a precipitation and aging process in an alcoholic solution. AB - In this paper, we detailed the formation/evolution of precipitates in alcoholic media containing Co(II+) and Li(+) species, together with the evolution of the composition and structure/texture of the resulting solid phases during the aging process at controlled constant temperature. While the end product is found to be well-crystallized HT-LiCoO(2), its formation is shown to result from a two-step process enlisting the initial fast precipitation of beta-HCoO(2) and then its slow dissolution followed by recrystallization of the lithium-containing material. These results were obtained through combined X-ray diffraction, Raman and IR spectroscopy, elemental and oxidation-state analysis, and high-resolution transmission electron microscopy/selected-area electron diffraction observations. Depending on the cationic concentration, the size of the precipitated material can be controlled within the nanometric range. The electrochemical performances of these aged materials are slightly improved compared to those of the directly precipitated ones that we previously reported. The main limitation of these materials remains the presence of surface protons. PMID- 21033688 TI - Crystal structures and magnetic properties of new europium melilites Eu(2)MSi(2)O(7) (M = Mg, Mn) and their strontium analogues. AB - Synthesis, crystal structures, and magnetic properties of melilite-type oxides A(2)MSi(2)O(7) (A = Sr, Eu; M = Mg, Mn) were investigated. These compounds crystallize in the melilite structure with space group P42(1)m. The (151)Eu Mossbauer measurements show that the Eu ions are in the divalent state. The Eu(2)MgSi(2)O(7) is paramagnetic down to 1.8 K. Long-range antiferromagnetic ordering is observed at 3.4 K for Sr(2)MnSi(2)O(7). On the other hand, the Eu(2)MnSi(2)O(7) shows a ferrimagnetic transition at 10.7 K. From the magnetization and specific heat measurements, it is found that the Eu(2+) (14 MU(B)) and Mn(2+) (5 MU(B)) sublattices order antiferromagnetically. This result indicates that an interaction between f-d electrons (Eu-Mn) predominantly operate in this compound. PMID- 21033690 TI - Self-assembly of colloidal quantum dots on the scaffold of triblock copolymer micelles. AB - This paper describes the co-self-assembly of a polystyrene-poly(4-vinylpyridine) poly(ethylene oxide) triblock copolymer with CdSe nanocrystals (quantum dots, QDs) and with a styrene compatible phenylenevinylene conjugated polymer (MEH-PPV) in mixtures of chloroform and 2-propanol. The polymer itself (PS(577)-P4VP(302) PEO(852), where the subscripts refer to the number average degree of polymerization) forms worm-like micelles when 2-propanol is added to a solution of the polymer in CHCl(3). In the presence of increasing amounts of QDs, the structures become shorter and form only spherical hybrid micelles (with QDs bound to the surface) at 4:1 QD/polymer w/w, accompanied by free QDs. These structures retain their colloidal stability in 2-PrOH, suggesting that even the free QDs bear a surface shell of block copolymer. The presence of MEH-PPV has no affect on this self assembly. One of the most remarkable observations occurred when the samples in 2-PrOH were centrifuged to remove the free QDs accompanying the hybrid micelles. The micelles sedimented, but upon redispersion in 2-PrOH, rearranged to form colloidally stable long branched cylindrical structures including cylindrical networks. PMID- 21033689 TI - Mechanism of inactivation of Escherichia coli aspartate aminotransferase by (S)-4 amino-4,5-dihydro-2-furancarboxylic acid . AB - As a potential drug to treat neurological diseases, the mechanism-based inhibitor (S)-4-amino-4,5-dihydro-2-furancarboxylic acid (S-ADFA) has been found to inhibit the gamma-aminobutyric acid aminotransferase (GABA-AT) reaction. To circumvent the difficulties in structural studies of a S-ADFA-enzyme complex using GABA-AT, l-aspartate aminotransferase (l-AspAT) from Escherichia coli was used as a model PLP-dependent enzyme. Crystal structures of the E. coli aspartate aminotransferase with S-ADFA bound to the active site were obtained via cocrystallization at pH 7.5 and 8. The complex structures suggest that S-ADFA inhibits the transamination reaction by forming adducts with the catalytic lysine 246 via a covalent bond while producing 1 equiv of pyridoxamine 5'-phosphate (PMP). Based on the structures, formation of the K246-S-ADFA adducts requires a specific initial binding configuration of S-ADFA in the l-AspAT active site, as well as deprotonation of the epsilon-amino group of lysine 246 after the formation of the quinonoid and/or ketimine intermediate in the overall inactivation reaction. PMID- 21033691 TI - Practical synthesis of PC190723, an inhibitor of the bacterial cell division protein FtsZ. AB - A high-yielding and practical synthesis of the bacterial cell division inhibitor PC190723 is described. The synthesis is completed in a longest linear sequence of five steps from commercially available starting materials and can be readily executed on a multigram scale. PMID- 21033692 TI - Direct carboxylation of arenes and halobenzenes with CO2 by the combined use of AlBr3 and R3SiCl. AB - The Lewis acid-mediated direct carboxylation of aromatic compounds with CO2 is efficiently promoted by the addition of silyl chlorides bearing three alkyl and/or aryl substituents in total on the silicon atom. Thus, toluene, xylenes, mesitylene, and some other alkylbenzenes are treated with a 1:1 mixture of AlBr3 and Ph3SiCl in neat substrates under CO2 pressure (3.0 MPa) at room temperature, to give the corresponding carboxylic acids in 60-97% yields, based on AlBr3. Polycyclic arenes, including naphthalene, phenanthrene, and biphenyl, are regioselectively carboxylated in 91-98% yields with the aid of 1 molar equiv of AlBr3 and Ph3SiCl in an appropriate solvent, chosen from benzene, chlorobenzene, and fluorobenzene. These solvents, as well as bromobenzene, resist carboxylation; however, they are also carboxylated in moderate yields when treated with a 1:5 mixture of AlBr3 and (i)PrSiCl at elevated temperatures. The FT-IR spectrum of a mixture prepared by exposing a suspension of AlBr3 and Ph3SiCl in cyclohexane to CO2 exhibits an absorption band around 1650 cm(-1), assigned to the C?O stretching vibration of a species consisting of CO2, AlBr3, and Ph3SiCl, which suggests that the silyl chlorides activate CO2 in cooperation with AlBr3. (1)H NMR analysis of unworked-up reaction mixtures reveals that the products merge as aluminum carboxylates. The mass balance concerning silicon indicates that the silyl chlorides are recycled during the reaction sequence. On the basis of these observations, a feasible mechanism is proposed for the present carboxylation. PMID- 21033693 TI - Unique crystalline/crystalline polymer blends of poly(ethylene succinate) and poly(p-dioxanone): miscibility and crystallization behaviors. AB - Miscibility and crystallization behaviors of poly(ethylene succinate)/poly(p dioxanone) (PES/PPDO) blends were investigated by differential scanning calorimetry (DSC), polarized optical microscopy (POM), and wide-angle X-ray diffraction (WAXD). PES/PPDO blends are completely miscible as proved by the single grass transition temperature (T(g)) dependence of composition and decreasing crystallization temperature of the blends in comparison with the respective component. POM observation suggests that simultaneous crystallization of PES and PPDO components in the blends took place, spherulites of one component can crystallize inside the spherulites of the other component, and the unique interpenetrated crystalline morphology has been formed for the blends in the full composition range. Isothermal crystallization kinetics of the blends was studied by DSC and the data were analyzed by the Avrami equation. The results suggest that the crystallization mechanisms of the blends were unchanged but the overall crystallization rates were slowed down compared with neat PES and neat PPDO. WAXD results indicate that the crystal structures of PES and PPDO did not change in the blends. PMID- 21033694 TI - Debunking some misconceptions about nanotoxicology. AB - Nanotechnology is currently undergoing an impressive expansion in material science research and development of systems that have novel properties due to their small size. Most of the research efforts have been focused on applications, while the implications efforts (i.e., environmental health and safety) have lagged behind. As a consequence, the success of nanotechnology will require assurances that the products being developed are safe from an environmental, health, and safety standpoint. These concerns have led to a debate among governmental agencies and advocacy groups on whether implementation of special regulations should be required for commercialization of products containing nanomaterials. Therefore the assessments of nanomaterial-related health risks must be accurate and verifiable. A mechanism for conducting well-designed toxicology studies includes rigorous attention to nanoparticle physicochemical characterization, as well as consideration of potential routes of exposure, justification of nanoparticle doses, and inclusion of benchmark controls. Unfortunately, some results obtained from earlier studies have fostered general perceptions and fears about nanoparticle health hazards-based mainly upon simple metrics such as particle size, surface area, and particle dose. In addition, there are currently held views that results of screening in silico or in vitro cell culture assays can serve as adequate screening substitutes for identifying health hazards. Some of these "misconceptions" should be challenged or confirmed by the implementation of thorough and accurately detailed nanotoxicology studies. In this article, the author briefly discusses some of the generalized "misconceptions" regarding nanomaterial toxicity and presents alternative views on these issues. PMID- 21033695 TI - Oriented growth of single-crystal Ni nanowires onto amorphous SiO2. AB - Highly oriented, single-crystal Ni nanowire arrays have been synthesized atop amorphous SiO2?Si substrates using a single-step chemical vapor deposition method in the absence of any foreign catalyst. Electron and X-ray diffraction confirm the crystalline quality of the Ni nanowires while magnetoresistance measurements probe the magnetic response and the behavior is explained using simulation results for nanoscale, single-crystal Ni. A growth mechanism involving competing chemical, energetic, and kinetic influences is presented. PMID- 21033696 TI - Synthesis of the spirochroman core of dihypoestoxide and stereochemical proposal for the natural product. AB - The tricyclic spirochroman core of dihypoestoxide has been synthesized from geranoic acid in seven steps using a hetero-Diels-Alder cycloaddition as a key step, thus providing support for the proposed biosynthesis of the natural product. Furthermore, analysis of the (13)C NMR data obtained for all four diastereoisomers of the synthetic spirochroman core has allowed us to propose a full stereochemical assignment for dihypoestoxide. PMID- 21033697 TI - Josiphos-catalyzed asymmetric homodimerization of ketoketenes. AB - In this paper the development of a chiral phosphine-catalyzed homodimerization of ketoketenes that provides access to a variety of highly substituted ketoketene dimer beta-lactones (11 examples) is reported. The Josiphos catalytic system displays good to excellent enantioselectivity (up to 96% ee). Ring-opening reactions of the enantioenriched ketoketene dimers were also carried out to access 1,3-diketones, enol esters, and beta-hydroxyketones with good diastereoselectivity. PMID- 21033698 TI - Improvement of insulin resistance by removal of systemic hydrogen peroxide by PEGylated catalase in obese mice. AB - Insulin resistance, a condition in which insulin action is impaired, is one of the characteristic features of type 2 diabetes. Excessive amounts of reactive oxygen species (ROS) interfere with the insulin signaling pathway, which leads to the progression of insulin resistance. To examine whether removal of systemic hydrogen peroxide is effective in improving insulin resistance, polyethylene glycol-conjugated catalase (PEG-catalase), a derivative with a long circulation half-life, was repeatedly injected into leptin-deficient ob/ob or high fat diet induced obese mice for 16 or 10 consecutive weeks, respectively. Although ob/ob mice gradually gained weight with time irrespective of the treatment, repeated intraperitoneal injections of PEG-catalase significantly reduced glucose levels in the fed state. Glucose and insulin tolerance tests also showed PEG-catalase significantly improved glucose tolerance and insulin sensitivity in ob/ob mice, respectively. Similar but less marked results were obtained in the diet-induced obese mice. Treatment of 3T3-L1 adipocytes with glucose oxidase (GO) increased lipid hydroperoxide formation and reduced insulin-stimulated Akt phosphorylation. Addition of catalase or PEG-catalase significantly inhibited the GO-induced changes in adipocytes. These findings indicate that systemic removal of hydrogen peroxide by PEG-catalase activates the insulin signaling pathway and improves insulin resistance in obese mice. PMID- 21033699 TI - A minimal Rac activation domain in the unconventional guanine nucleotide exchange factor Dock180. AB - Guanine nucleotide exchange factors (GEFs) activate Rho GTPases by catalyzing the exchange of bound GDP for GTP, thereby resulting in downstream effector recognition. Two metazoan families of GEFs have been described: Dbl-GEF family members that share conserved Dbl homology (DH) and Pleckstrin homology (PH) domains and the more recently described Dock180 family members that share little sequence homology with the Dbl family and are characterized by conserved Dock homology regions 1 and 2 (DHR-1 and -2, respectively). While extensive characterization of the Dbl family has been performed, less is known about how Dock180 family members act as GEFs, with only a single X-ray structure having recently been reported for the Dock9-Cdc42 complex. To learn more about the mechanisms used by the founding member of the family, Dock180, to act as a Rac specific GEF, we set out to identify and characterize its limit functional GEF domain. A C-terminal portion of the DHR-2 domain, composed of approximately 300 residues (designated as Dock180(DHR-2c)), is shown to be necessary and sufficient for robust Rac-specific GEF activity both in vitro and in vivo. We further show that Dock180(DHR-2c) binds to Rac in a manner distinct from that of Rac-GEFs of the Dbl family. Specifically, Ala(27) and Trp(56) of Rac appear to provide a bipartite binding site for the specific recognition of Dock180(DHR-2c), whereas for Dbl family Rac-GEFs, Trp(56) of Rac is the sole primary determinant of GEF specificity. On the basis of our findings, we are able to define the core of Dock180 responsible for its Rac-GEF activity as well as highlight key recognition sites that distinguish different Dock180 family members and determine their corresponding GTPase specificities. PMID- 21033700 TI - A novel DNA topoisomerase I inhibitor with different mechanism from camptothecin induces G2/M phase cell cycle arrest to K562 cells. AB - DNA topoisomerase I (Top1) is an essential nuclear enzyme and a validated target for anticancer agent screening. In a previous study, we found that indolizinoquinoline-5,12-dione derivatives show significant biological activity against several human cancer cell lines. To understand their mechanism of inhibition of cancer cell growth, one indolizinoquinoline-5,12-dione derivative, CY13II, was further studied as lead. Our present results indicate that CY13II shows more potent antiproliferative activity against K562 cells than camptothecin. Additionally, K562 cells were arrested in G2/M, and their growth rate decreased after treatment with CY13II at micromolar concentration. Biochemical Top1 assays indicate that CY13II exhibits a different inhibitory mechanism from camptothecin. Unlike camptothecin, CY13II specifically inhibits the catalytic cleavage activity of Top1 instead of forming the drug-enzyme-DNA covalent ternary complex. PMID- 21033701 TI - Iodine-mediated solvent-controlled selective electrophilic cyclization and oxidative esterification of o-alkynyl aldehydes: an easy access to pyranoquinolines, pyranoquinolinones, and isocumarins. AB - Chemoselective behavior of iodine in different solvents in the electrophilic iodocyclization of o-alkynyl aldehydes is described. o-Alkynyl aldehydes 3a-t on reaction with I2 in CH2Cl2 with appropriate nucleophiles provides pyrano[4,3 b]quinolines 4a-f, via formation of cyclic iodonium intermediate Q; however, using alcohols as a solvent as well as nucleophile, o-alkynyl esters 5a-y were obtained selectively in good to excellent yields via formation of hypoiodide intermediate R. Subsequently, o-alkynyl esters were converted in to pyranoquinolinones 6a-i and isocoumarin 6j by electrophilic iodocyclization. This developed oxidative esterification provides a novel access for the chemoselective synthesis of esters 5q-u from aldehydes 3n-p without oxidizing primary alcohol present in the substrate. PMID- 21033702 TI - One-pot enantioselective syntheses of iminosugar derivatives using organocatalytic anti-michael-anti-aza-Henry reactions. AB - Organocatalyst-controlled asymmetric anti-Michael reactions of (tert butyldimethylsilyloxy)acetaldehyde with a range of nitroolefins, followed by an intermolecular aza-Henry reaction with imine, provided iminosugar derivatives with five contiguous stereocenters in very high enantiomeric excess in one pot. The stereochemistry of the aza-Henry reaction was substrate controlled and is explained by a six-membered cyclic transition-state model. PMID- 21033703 TI - Ag(9) quantum cluster through a solid-state route. AB - A silver cluster having the composition Ag(9)(H(2)MSA)(7) (H(2)MSA = mercaptosuccinic acid) was synthesized in macroscopic quantities using a solid state route. The clusters were purified by PAGE and characterized by UV-vis, FTIR, luminescence, and NMR spectroscopy, TEM, XPS, XRD, TG, SEM/EDAX, elemental analysis, and ESI MS. The solid-state route provides nearly pure Ag(9) clusters, and nanoparticle contamination was insignificant for routine studies. Formation of various clusters was observed by modifying the conditions. The effect of ligands on the synthesis was checked. The cluster decomposed slowly in water, and the decomposition followed first-order kinetics. However, it could be stabilized in solvent mixtures and in the solid state. Such materials may be important in cluster research because of their characteristic absorption profiles, which are similar to those of Au(25) and Au(38). The cluster showed luminescence with a quantum yield of 8 * 10(-3) at 5 degrees C. PMID- 21033704 TI - Synthesis, reactivity, and electronic properties of 6,6-dicyanofulvenes. AB - A series of 6,6-dicyanofulvene derivatives are synthesized starting from masked, dimeric, or monomeric cyclopentadienones. The reactivities of 6,6-dicyanofulvenes relative to their parent cyclopentadienones are discussed. 6,6-Dicyanofulvenes are capable of undergoing two consecutive, reversible, one-electron reductions and are presented as potential n-type small molecules. PMID- 21033705 TI - First hyperpolarizability dispersion of the octupolar molecule crystal violet: multiple resonances and vibrational and solvation effects. AB - The first hyperpolarizability (beta) dispersion curve is measured for the first time for an octupolar nonlinear optical (NLO) molecule (crystal violet, CV) and modeled theoretically, yielding an in-depth understanding of the electronic structure and vibronic and solvation effects on such octupolar conjugated systems. Tunable wavelength hyper-Rayleigh scattering (HRS) measurements were performed on this prototypical octupolar molecule in the broad fundamental wavelength range of 620-1580 nm, showing significant shortcomings of the commonly used beta dispersion models. Three well-separated beta resonances involving the lowest-energy state and several higher excited states are clearly observed, including a significant contribution from a nominally one-photon forbidden transition. The experimental results for second-harmonic wavelengths above 330 nm are successfully modeled by means of a vibronically coupled essential-state description for octupolar chromophores, developed by Terenziani et al. (J. Phys. Chem. B 2008, 112, 5079), which takes into account polar solvation effects. The relative intensities of the various resonances, including the one below 330 nm, are also quantified by quantum chemical calculations. Furthermore, interesting effects of inhomogeneous broadening due to polar solvation of the two-dimensional chromophore are recognized in both linear and nonlinear spectra, allowing us to quantitatively address the long-standing problem of the band shape of the linear absorption spectrum of CV. This clearly demonstrates that extensive wavelength dependent HRS measurements, as presented in this work, are essential to the characterization and design of NLO materials and represent a powerful tool to gain valuable information on molecular excitations and environmental effects in general. PMID- 21033706 TI - Artificial Golgi apparatus: globular protein-like dendrimer facilitates fully automated enzymatic glycan synthesis. AB - Despite the growing importance of synthetic glycans as tools for biological studies and drug discovery, a lack of common methods for the routine synthesis remains a major obstacle. We have developed a new method for automated glycan synthesis that employs the enzymatic approach and a dendrimer as an ideal support within the chemical process. Recovery tests using a hollow fiber ultrafiltration module have revealed that monodisperse G6 (MW = 58 kDa) and G7 (MW = 116 kDa) poly(amidoamine) dendrimers exhibit a similar profile to BSA (MW = 66 kDa). Characteristics of the globular protein-like G7 dendrimer with high solubility and low viscosity in water greatly enhanced throughput and efficiency in automated synthesis while random polyacrylamide-based supports entail significant loss during the repetitive reaction/separation step. The present protocol allowed for the fully automated enzymatic synthesis of sialyl Lewis X tetrasaccharide derivatives over a period of 4 days in 16% overall yield from a simple N-acetyl-d glucosamine linked to an aminooxy-functionalized G7 dendrimer. PMID- 21033707 TI - Mechanistic and computational study of a palladacycle-catalyzed decomposition of a series of neutral phosphorothioate triesters in methanol. AB - The methanolytic cleavage of a series of O,O-dimethyl O-aryl phosphorothioates (1a-g) catalyzed by a C,N-palladacycle, (2-[N,N-dimethylamino(methyl)phenyl] C1,N)(pyridine) palladium(II) triflate (3), at 25 degrees C and sspH 11.7 in methanol is reported, along with data for the methanolytic cleavage of 1a-g. The methoxide reaction gives a linear log k2-OMe vs sspKa (phenol leaving group) Bronsted plot having a gradient of betalg = -0.47 +/- 0.03, suggesting about 34% cleavage of the P-OAr bond in the transition state. On the other hand, the 3 catalyzed cleavage of 1 gives a Bronsted plot with a downward break at sspKa (phenol) 13, signifying a change in the rate-limiting step in the catalyzed reaction, with the two wings having betalg values of 0.0 +/- 0.03 and -1.93 +/- 0.06. The rate-limiting step for good substrates with low leaving group sspKa values is proposed to be substrate/pyridine exchange on the palladacycle, while for substrates with poor leaving groups, the rate-limiting step is a chemical one with extensive cleavage of the P-OAr bond. DFT calculations support this process and also identify two intermediates, namely, one where substrate/pyridine interchange has occurred to give the palladacycle coordinated to substrate through the S?P linkage and to methoxide (6) and another where intramolecular methoxide attack has occurred on the P?S unit to give a five-coordinate phosphorane (7) doubly coordinated to Pd via the S- and through a bridging methoxide linked to P and Pd. Attempts to identify the existence of the phosphorane by 31P NMR in a d4-methanol solution containing 10 mM each of 3, trimethyl phosphorothioate (a very slow cleaving substrate), and methoxide proved unsuccessful, instead showing that the phosphorothioate was slowly converted to trimethyl phosphate, with the palladacycle decomposing to Pd0 and free pyridine. These results provide the first reported example where a palladacycle-promoted solvolysis reaction exhibits a break in the Bronsted plot signifying at least one intermediate, while the DFT calculations provide further insight into a more complex mechanism involving two intermediates. PMID- 21033709 TI - A porphyrin nanobarrel that encapsulates C(60). AB - A porphyrin nanobarrel, 1, that can encapsulate C(60) effectively was prepared via a concise coupling route. The structures of both 1 and C(60)@1 were confirmed by single-crystal X-ray diffraction analysis. PMID- 21033710 TI - Processing and storage effects on the ellagitannin composition of processed blackberry products. AB - Changes in blackberry ellagitannin composition in response to juicing (clarified and nonclarified), pureeing, canning (in water or syrup), and freezing as well as changes in processed products during 6 months of storage were investigated. Canning, pureeing, and freezing had little effect on ellagitannins, but processing berries into nonclarified and clarified juices resulted in total ellagitannin losses of 70 and 82%, respectively, due to removal of ellagitannin rich seeds in the presscake. Minimal changes in total ellagitannin content were observed during storage of thermally processed products, but compositional changes indicative of ellagitannin depolymerization were apparent. The ellagitannin content and composition of frozen berries remained stable over 6 months of storage. Ellagitannins are well retained in canned, pureed, and frozen blackberries, but methods are needed to prevent losses during juice processing and/or exploit the ellagitannin-rich coproducts. PMID- 21033708 TI - Biofunctionalization on alkylated silicon substrate surfaces via "click" chemistry. AB - Biofunctionalization of silicon substrates is important to the development of silicon-based biosensors and devices. Compared to conventional organosiloxane films on silicon oxide intermediate layers, organic monolayers directly bound to the nonoxidized silicon substrates via Si-C bonds enhance the sensitivity of detection and the stability against hydrolytic cleavage. Such monolayers presenting a high density of terminal alkynyl groups for bioconjugation via copper-catalyzed azide-alkyne 1,3-dipolar cycloaddition (CuAAC, a "click" reaction) were reported. However, yields of the CuAAC reactions on these monolayer platforms were low. Also, the nonspecific adsorption of proteins on the resultant surfaces remained a major obstacle for many potential biological applications. Herein, we report a new type of "clickable" monolayers grown by selective, photoactivated surface hydrosilylation of alpha,omega-alkenynes, where the alkynyl terminal is protected with a trimethylgermanyl (TMG) group, on hydrogen-terminated silicon substrates. The TMG groups on the film are readily removed in aqueous solutions in the presence of Cu(I). Significantly, the degermanylation and the subsequent CuAAC reaction with various azides could be combined into a single step in good yields. Thus, oligo(ethylene glycol) (OEG) with an azido tag was attached to the TMG-alkyne surfaces, leading to OEG terminated surfaces that reduced the nonspecific adsorption of protein (fibrinogen) by >98%. The CuAAC reaction could be performed in microarray format to generate arrays of mannose and biotin with varied densities on the protein resistant OEG background. We also demonstrated that the monolayer platform could be functionalized with mannose for highly specific capturing of living targets (Escherichia coli expressing fimbriae) onto the silicon substrates. PMID- 21033711 TI - Enantioenriched synthesis of cyclopropenes with a quaternary stereocenter, versatile building blocks. AB - Ir(salen) complexes were found to catalyze enantioselective cyclopropenation efficiently. Cyclopropenation can be carried out using either a donor/acceptor- or an acceptor/acceptor-substituted diazo compound such as alpha-aryl-alpha diazoacetates, alpha-phenyl-alpha-diazophosphonate, 2,2,2-trifluoro-1-phenyl-1 diazoethane, and alpha-cyano-alpha-diazoacetamide as carbenoid precursors. The reactions provide highly enantioenriched cyclopropenes (84-98% ee) with a functionalized quaternary carbon as versatile building blocks. PMID- 21033712 TI - Structural characterization and hypoglycemic effects of arabinogalactan-protein from the tuberous cortex of the white-skinned sweet potato (Ipomoea batatas L.). AB - An arabinogalactan-protein (WSSP-AGP) was isolated from the tuberous cortex of the white-skinned sweet potato (WSSP; Ipomoea batatas L.). It consists of 95% (w/w) carbohydrate and 5% (w/w) protein with high contents of hydroxyproline, alanine, and serine. Its sugar composition is alpha-L-Rha:alpha-L-Ara:beta-D Gal:beta-D-GlcA in a molar ratio of 1.0:4.1:7.6:1.3. Its weight-average molecular weight was estimated to be 126,800 g/mol by high-performance size exclusion chromatography coupled with multiangle laser light scattering. Structural analysis indicated that WSSP-AGP is a (1->3)-beta-D-galactan highly branched at O 6 with (1->6)-beta-D-galactan, in which the branched chains are substituted at the O-3 position with alpha-L-Araf-(1-> and alpha-L-Araf-(1->5)-alpha-L-Araf-(1-> and at the O-6 position typically with alpha-L-Rhap-(1->4)-beta-D-GlcAp-(1-> as terminating groups. Continuous administration of WSSP-AGP to KKAy mice significantly lowered fasting plasma glucose levels. This indicates that WSSP-AGP plays an important role in the hypoglycemic effects of WSSP. PMID- 21033713 TI - Crystallinity of purple membranes comprising the chloride-pumping bacteriorhodopsin variant D85T and its modulation by pH and salinity. AB - Self-assembly of membrane proteins inside the cell membrane critically depends on specific protein-protein and protein-lipid interactions. Purple membranes (PMs) from Halobacterium salinarum comprise wild-type bacteriorhodopsin (BR) and lipids only and form a 2-D crystalline lattice of P3 symmetry in the cell membrane. It is known that removal of the retinylidene residue as well as the exchange of selected amino acids lead to a loss of crystallinity. In PMs comprising the BR variant D85T, we have observed a tunable tendency to form crystalline domains, which depends on pH-value and chloride ion concentration. BR-D85T resembles the function of the chloride pump halorhodopsin. The protonation state of amino acid residues within the binding pocket and chloride binding in the vicinity of the protonated retinal Schiff base affect the overall shape of BR-D85T molecules in the membrane, thereby changing their interactions and subsequently their tendency to form crystalline areas. The combination of small-angle X-ray scattering, atomic force microscopy, and freeze-fracture electron microscopy enables us to analyze the transitions statistically as well as on the single membrane level. PM D85T is a model system to study membrane protein association upon substrate binding in a native environment. Furthermore, the ability to reversibly modulate the crystallinity of PMs probably will be useful for the preparation of larger artificial crystalline arrays of BR and its variants. PMID- 21033714 TI - Manipulating double-decker molecules at the liquid-solid interface. AB - We have used a scanning tunneling microscope (STM) to manipulate heteroleptic phthalocyaninato, naphthalocyaninato, and porphyrinato double-decker (DD) molecules at the liquid-solid interface between 1-phenyloctane solvent and graphite. We employed nanografting of phthalocyanines with eight octyl chains to place these molecules into a matrix of heteroleptic DD molecules; the overlayer structure is epitaxial on graphite. We have also used nanografting to place DD molecules in matrices of single-layer phthalocyanines with octyl chains. Rectangular scans with a STM at low bias voltage resulted in the removal of the adsorbed DD molecular layer and substituted the DD molecules with bilayer-stacked phthalocyanines from phenyloctane solution. Single heteroleptic DD molecules with lutetium sandwiched between naphthalocyanine and octaethylporphyrin were decomposed with voltage pulses from the probe tip; the top octaethylporphyrin ligand was removed, and the bottom naphthalocyanine ligand remained on the surface. A domain of decomposed molecules was formed within the DD molecular domain, and the boundary of the decomposed molecular domain self-cured to become rectangular. We demonstrated a molecular "sliding block puzzle" with cascades of DD molecules on the graphite surface. PMID- 21033716 TI - p67/MetAP2 suppresses K-RasV12-mediated transformation of NIH3T3 mouse fibroblasts in culture and in athymic mice. AB - In many tumor cells, the activation and activity of extracellular signal regulated kinases (ERK1/2) are very high because of the constitutive activation of the Ras-mediated signaling pathway. Here, we ectopically expressed the human homologue of rat eukaryotic initiation factor 2-associated glycoprotein, p67/MetAP2, in EGF-treated mouse embryonic NIH3T3 fibroblasts and C2C12 myoblasts and NIH3T3 cell lines expressing the constitutively active form of MAP kinase kinase (MEK) to inhibit the activation and activity of ERK1/2 MAP kinases. In addition, we also ectopically expressed rat p67/MetAP2 in oncogenic Ras-induced transformed NIH3T3 fibroblasts and inhibited their transformed phenotype both in culture and in athymic nude mice possibly by inhibiting angiogenesis. This inhibition of ERK1/2 MAP kinases is due to the direct binding with rat p67/MetAP2, and this leads to the inhibition of activity of ERK1/2 MAP kinases both in vitro and in vivo. Furthermore, expression of p67/MetAP2 siRNA in both NIH3T3 fibroblasts and C2C12 myoblasts causes activation and activity of ERK1/2 MAP kinases. Our results thus suggest that ectopic expression of rat p67/MetAP2 in transformed cells can inhibit the tumorigenic phenotype by inhibiting the activation and activity of ERK1/2 MAP kinases and, thus, that p67/MetAP2 has tumor suppression activity. PMID- 21033717 TI - Two-step Hantzsch based macrocyclization approach for the synthesis of thiazole containing cyclopeptides. AB - Macrocyclization via an efficient high-yielding solid-phase intramolecular thioalkylation reaction is described. The reaction of S-nucleophiles with newly generated N-terminal 4-chloromethyl thiazoles led to the desired macrocyclization products 5 in high purities and good overall yields. PMID- 21033718 TI - Regio- and enantioselective intermolecular hydroacylation: substrate-directed addition of salicylaldehydes to homoallylic sulfides. AB - We report a Rh-catalyzed, regio- and enantioselective intermolecular olefin hydroacylation under mild conditions. Hydroacylations between homoallylic sulfides, containing a substrate-bound directing group, and salicylaldehyde derivatives occur in the presence of a spiro-phosphoramidite ligand, (R)-SIPHOS PE, to give alpha-branched ketones in >20:1 selectivity and up to 97% ee. Our conditions are also applicable to the asymmetric intermolecular hydroacylation of 1,2-disubstituted olefins. PMID- 21033719 TI - On the analogy of B-BO and B-Au chemical bonding in B11O- and B10Au- clusters. AB - During photoelectron spectroscopy experiments, the spectra of B(11)O(-) and B(10)Au(-) clusters are found to exhibit similar patterns except for a systematic spectral shift of ~0.5 eV, hinting that they possess similar geometric structures. The electron affinities are measured to be 4.02 +/- 0.04 eV for B(11)O and 3.55 +/- 0.02 eV for B(10)Au. DFT calculations at the B3LYP level show that B(11)O(-) and B(10)Au(-) adopt similar C(1) ((1)A) ground states, which are based on the quasiplanar B(10) cluster interacting with a BO unit and Au, respectively. The B(11)O(-) and B(10)Au(-) clusters are thus valent isoelectronic because both BO and Au can be viewed as monovalent units, forming highly covalent B-BO and B-Au bonds analogous to the B-H bond in B(10)H(-). For B(10)Au(-), we also find a highly symmetric D(10h) ((1)A(1g)) planar molecular wheel as a minimum on the potential energy surface. However, it is 45 kcal/mol above the ground state at the B3LYP level and not viable for experimental observation. Natural bond orbital analyses reveal interesting covalent versus ionic B-Au bonding in the C(1) B(10)Au(-) and D(10h) B(10)Au(-) structures, respectively, providing insight for the design of D(nh) MB(n) molecular wheels. PMID- 21033720 TI - Maple syrup phytochemicals include lignans, coumarins, a stilbene, and other previously unreported antioxidant phenolic compounds. AB - Twenty-three phenolic compounds were isolated from a butanol extract of Canadian maple syrup (MS-BuOH) using chromatographic methods. The compounds were identified from their nuclear magnetic resonance and mass spectral data as 7 lignans [lyoniresinol (1), secoisolariciresinol (2), dehydroconiferyl alcohol (3), 5'-methoxy-dehydroconiferyl alcohol (4), erythro-guaiacylglycerol-beta-O-4' coniferyl alcohol (5), erythro-guaiacylglycerol-beta-O-4'-dihydroconiferyl alcohol (6), and [3-[4-[(6-deoxy-alpha-l-mannopyranosyl)oxy]-3 methoxyphenyl]methyl]-5-(3,4-dimethoxyphenyl)dihydro-3-hydroxy-4-(hydroxymethyl) 2(3H)-furanone (7)], 2 coumarins [scopoletin (8) and fraxetin (9)], a stilbene [(E)-3,3'-dimethoxy-4,4'-dihydroxystilbene (10)], and 13 phenolic derivatives [2 hydroxy-3',4'-dihydroxyacetophenone (11), 1-(2,3,4-trihydroxy-5 methylphenyl)ethanone (12), 2,4,5-trihydroxyacetophenone (13), catechaldehyde (14), vanillin (15), syringaldehyde (16), gallic acid (17), trimethyl gallic acid methyl ester (18), syringic acid (19), syringenin (20), (E)-coniferol (21), C veratroylglycol (22), and catechol (23)]. The antioxidant activities of MS-BuOH (IC50>1000 MUg/mL), pure compounds, vitamin C (IC50=58 MUM), and a synthetic commercial antioxidant, butylated hydroxytoluene (IC50=2651 MUM), were evaluated in the diphenylpicrylhydrazyl (DPPH) radical scavenging assay. Among the isolates, the phenolic derivatives and coumarins showed superior antioxidant activity (IC50<100 MUM) compared to the lignans and stilbene (IC50>100 MUM). Also, this is the first report of 16 of these 23 phenolics, that is, compounds 1, 2, 4-14, 18, 20, and 22, in maple syrup. PMID- 21033721 TI - Relationship between rheological properties and one-step W/O/W multiple emulsion formation. AB - Formation of a normal (not temporary) W/O/W multiple emulsion via the one-step method as a result of the simultaneous occurrence of catastrophic and transitional phase inversion processes has been recently reported. Critical features of this process include the emulsification temperature (corresponding to the ultralow surface tension point), the use of a specific nonionic surfactant blend and the surfactant blend/oil phase ratio, and the addition of the surfactant blend to the oil phase. The purpose of this study was to investigate physicochemical properties in an effort to gain a mechanistic understanding of the formation of these emulsions. Bulk, surface, and interfacial rheological properties of adsorbed nonionic surfactant (CremophorRH40 and Span80) films were investigated under conditions known to affect W/O/W emulsion formation. Bulk viscosity results demonstrated that CremophorRH40 has a higher mobility in oil compared than in water, explaining the significance of the solvent phase. In addition, the bulk viscosity profile of aqueous solutions containing CremophorRH40 indicated a phase transition at around 78 +/- 2 degrees C, which is in agreement with cubic phase formation in the Winsor III region. The similarity in the interfacial elasticity values of CremophorRH40 and Span80 indicated that canola oil has a major effect on surface activity, showing the significance of vegetable oil. The highest interfacial shear elasticity and viscosity were observed when both surfactants were added to the oil phase, indicating the importance of the microstructural arrangement. CremophorRH40/Span80 complexes tended to desorb from the solution/solution interface with increasing temperature, indicating surfactant phase formation as is theoretically predicted in the Winsor III region. Together these interfacial and bulk rheology data demonstrate that one-step W/O/W emulsions form as a result of the simultaneous occurrence of phase-transition processes in the Winsor III region and explain the critical formulation and processing parameters necessary to achieve the formation of these normal W/O/W emulsions. PMID- 21033722 TI - Total synthesis of diptoindonesin G via a highly efficient domino cyclodehydration/intramolecular Friedel-Crafts acylation/regioselective demethylation sequence. AB - A highly efficient total synthesis of diptoindonesin G is described employing a domino dehydrative cyclization/intramolecular Friedel-Crafts acylation/regioselective demethylation reaction of aryloxyketone 7 by the action of BCl(3) wherein the tetracyclic 6H-anthra[1,9-bc]furan-6-one skeleton was constructed via the 3-arylbenzofuran in a one-pot manner. This is the first example of the strategic combination of these three reactions in a cascade fashion. The routes presented here allow for direct access to diptoindonesin G and its analogues. PMID- 21033724 TI - A concise access to 3-substituted 2-pyrones. AB - The development of a modular synthesis of 3-substituted-2-pyrones is described. The attainment of this strategy hinges on a new electrophilic pyrone derivative which can be readily prepared on a multigram scale and which performs very competently in metal-catalyzed cross-coupling reactions with a variety of nucleophiles. PMID- 21033725 TI - Transition-metal-doped aluminum hydrides as building blocks for supramolecular assemblies. AB - Density functional theory calculations were carried out to characterize a series of transition-metal-doped aluminum hydrides, forming TMAl(n)H(2n) and TMAl(n)H(2n+1) (TM = Sc, Ti, V; n = 3,4), in either charged or neutral form. A new electron-counting rule for these clusters was formulated as PSEN (paired skeleton electron number) = 4n, which can characterize both closed-shell and open shell clusters. On the basis of this electron-counting rule, the superatomic clusters such as TiAl(4)H(9) and TiAl(3)H(6) were identified and can be used to assemble supramolecular structures. Electronic structure analysis showed that three-centered TM-H-Al bonds largely contributed to the structural stability. Also, the spin state of a wide range of clusters in their ground state can be predicted by the electron-counting rule. PMID- 21033723 TI - Total synthesis of Lys(3) tamandarin M: a potential affinity ligand. AB - The synthesis of Lys(3) tamandarin M is described. This analogue can be used as a protein affinity ligand to probe the mechanism of action of this unique class of molecules. PMID- 21033726 TI - Regulation of influenza RNA polymerase activity and the switch between replication and transcription by the concentrations of the vRNA 5' end, the cap source, and the polymerase. AB - The influenza RNA-dependent RNA polymerase (RdRp) both replicates the flu's RNA genome and transcribes its mRNA. Replication occurs de novo; however, initiation of transcription requires a 7-methylguanosine 5'-capped primer that is "snatched" from host mRNA via endonuclease and cap binding functions of the influenza polymerase. A key question is how the virus regulates the relative amounts of transcription and replication. We found that the concentration of a capped cellular mRNA, the concentration of the 5' end of the viral RNA, and the concentration of RdRp all regulate the relative amounts of replication versus transcription. The host mRNA, from which the RdRp snatches its capped primer, acts to upregulate transcription and repress replication. Elevated concentrations of the RdRp itself switch the influenza polymerase toward replication, likely through an oligomerization of the polymerase. The 5' end of the vRNA template both activates replication and inhibits transcription of the vRNA template, thereby indicating that RdRp contains an allosteric binding site for the 5' end of the vRNA template. These data provide insights into the regulation of RdRp throughout the viral life cycle and how it synthesizes the appropriate amounts of viral mRNA and replication products (vRNA and cRNA). PMID- 21033728 TI - Catalytic enantioselective synthesis of secondary allylic alcohols from terminal alkynes and aldehydes via 1-alkenylboron reagents. AB - A practical one-pot method has been developed for preparing enantioenriched secondary allylic alcohols starting from terminal alkynes and aldehydes. Hydroboration of terminal alkynes with dicyclohexylborane and subsequent reaction of the resulting alkenylboron reagents with aldehydes in the presence of a catalytic amount (5 mol %) of 3-(3,5-diphenylphenyl)-H(8)-BINOL and excess titanium tetraisopropoxide afforded the corresponding allylic alcohols in high enantioselectivities up to 94% ee. PMID- 21033727 TI - Highly selective ratiometric fluorescent sensing for Hg(2+) and Au(3+), respectively, in aqueous media. AB - A nonsulfur probe based on a 1,8-naphthalimide and alkyne conjugate for the ratiometric fluorescent sensing for Hg(2+) and Au(3+) through the tuning of pH in different aqueous solutions is described. This work provides a novel reaction based approach for selective recognition of these two ions with significant change of fluorescence color and constitutes the first ratiometric case for Au(3+). PMID- 21033729 TI - Loss of ammonia during electron-transfer dissociation of deuterated peptides as an inherent gauge of gas-phase hydrogen scrambling. AB - The application of electron-transfer dissociation (ETD) to obtain single-residue resolution in hydrogen exchange-mass spectrometry (HX-MS) experiments has recently been demonstrated. For such measurements, it is critical to ensure that the level of gas-phase hydrogen scrambling is negligible. Here we utilize the abundant loss of ammonia upon ETD of peptide ions as a universal reporter of positional randomization of the exchangeable hydrogens (hydrogen scrambling) during HX-ETD experiments. We show that the loss of ammonia from peptide ions proceeds without depletion of deuterium when employing optimized mild electrospray ion source settings for the HX-ETD analysis of a selectively labeled model peptide and peptides derived from fully labeled beta(2)-microglobulin. Hydrogen scrambling, as induced by excessive vibrational excitation of peptide ions during harsh declustering conditions, is easily detected by a depletion of deuterium when deuterated ammonia is lost from peptides during ETD. This straightforward method requires no modifications to the experimental workflow and has the great advantage that the occurrence of hydrogen scrambling can be directly detected in the actual peptides analyzed in the HX-ETD experiment. PMID- 21033730 TI - A diastereoselective three-component coupling approach to highly substituted pyrrolidines. AB - Building on the observation that metal complexation facilitates azomethine ylide formation, we report that chelating aldehydes participate in metal-templated, one pot reactions with unprotected amino acid esters and activated olefins to provide highly substituted pyrrolidines. The high yields, broad substrate scope, excellent diastereoselectivities, functional group tolerance, and incorporation of commercially available materials in this reaction simplifies access to medicinally relevant proline derivatives. PMID- 21033731 TI - Formation of sulfonated aromatic ketone chromophores within styrene-acrylic acid copolymers and their pH-responsive color change. AB - Styrene-acrylic acid copolymer was synthesized via solution polymerization and then sulfonated by concentrated sulfuric acid. This sulfonated copolymer displays an obvious pH-responsive color change in aqueous solutions (1 g/L) from yellow (pH <6) to khaki (pH 6 to 7)/red (pH 7 to 8) to purple (pH >8). This response is as quick as for small-molecule pH indicators such as methyl orange and phenolphthalein within 1 s and can be reversible. The lowest critical concentration of this pH-responsive copolymer solution is around 0.1 g/L, which is about 50-500 times the necessary amount used for conventional small-molecule pH indicators. An intramolecular cyclization mechanism between a neighboring carboxyl group and a benzene ring to form a sulfonated aromatic ketone is proposed to explain this pH-responsive color change behavior. The molar ratio of 1:1 for styrene to acrylic acid is the most favorable for forming neighboring benzene and carboxyl group pairs in the copolymer chains and subsequently yields sulfonated aromatic ketone chromophores at full capacity. PMID- 21033733 TI - Thermally induced electrocyclic reaction of methylenecyclopropane methylene diketone derivatives: a facile method for the synthesis of spiro[2.5]octa-3,5 dienes. AB - Thermally induced electrocyclic reactions of methylenecyclopropane (MCP) methylene diketone derivatives afford a novel method for the synthesis of spiro[2.5]octa-3,5-dienes in moderate to good yields. Applying this methodology in a one-pot manner for the reactions of MCP aldehydes with 1,3-diketones, catalyzed by l-proline, also afforded the corresponding spiro derivatives. PMID- 21033732 TI - Coating colloidal carbon spheres with CdS nanoparticles: microwave-assisted synthesis and enhanced photocatalytic activity. AB - This manuscript describes the accurate coating of CdS nanoparticles on the surface of colloidal carbon spheres by a facile two-step, microwave-assisted method and the studies on the photocatalytic activity of the C@CdS core-shell spheres. For the coating of CdS nanoparticles, cadmium ions were incorporated into the hydrophilic shell of colloidal carbon spheres and reacted with an introduced sulfur source under a microwave field to obtain the C@CdS hybrid spheres. Using this process, the as-prepared hybrid structures preserved the good dispersity and uniformity of initial carbon spheres, and the thickness of the CdS nanoparticles shell could be varied or controlled by the irradiation time. A photoluminescence spectrum showed that the C@CdS hybrid spheres feature a broad green emission at around 494 nm (lambda(ex) = 337 nm). Additionally, CdS nanospheres were successfully prepared in aqueous solution via a microwave assisted route, and the effect of irradiation time on the products was also investigated. The studies of the photocatalytic property demonstrate that these fabricated functional hybrid structures evinced a higher photocatalytic degradation activity when exposed to visible light irradiation than that of CdS nanospheres under the same conditions. PMID- 21033734 TI - Surface area and the seabed area, volume, depth, slope, and topographic variation for the world's seas, oceans, and countries. AB - Depth and topography directly and indirectly influence most ocean environmental conditions, including light penetration and photosynthesis, sedimentation, current movements and stratification, and thus temperature and oxygen gradients. These parameters are thus likely to influence species distribution patterns and productivity in the oceans. They may be considered the foundation for any standardized classification of ocean ecosystems and important correlates of metrics of biodiversity (e.g., species richness and composition, fisheries). While statistics on ocean depth and topography are often quoted, how they were derived is rarely cited, and unless calculated using the same spatial resolution the resulting statistics will not be strictly comparable. We provide such statistics using the best available resolution (1-min) global bathymetry, and open source digital maps of the world's seas and oceans and countries' Exclusive Economic Zones, using a standardized methodology. We created a terrain map and calculated sea surface and seabed area, volume, and mean, standard deviation, maximum, and minimum, of both depth and slope. All the source data and our database are freely available online. We found that although the ocean is flat, and up to 71% of the area has a < 1 degree slope. It had over 1 million approximately circular features that may be seamounts or sea-hills as well as prominent mountain ranges or ridges. However, currently available global data significantly underestimate seabed slopes. The 1-min data set used here predicts there are 68,669 seamounts compared to the 30,314 previously predicted using the same method but lower spatial resolution data. The ocean volume exceeds 1.3 billion km(3) (or 1.3 sextillion liters), and sea surface and seabed areas over 354 million km(2). We propose the coefficient of variation of slope as an index of topographic heterogeneity. Future studies may improve on this database, for example by using a more detailed bathymetry, and in situ measured data. The database could be used to classify ocean features, such as abyssal plains, ridges, and slopes, and thus provide the basis for a standards based classification of ocean topography. PMID- 21033735 TI - Pb isotopes as an indicator of the Asian contribution to particulate air pollution in urban California. AB - During the last two decades, expanding industrial activity in east Asia has led to increased production of airborne pollutants that can be transported to North America. Previous efforts to detect this trans-Pacific pollution have relied upon remote sensing and remote sample locations. We tested whether Pb isotope ratios in airborne particles can be used to directly evaluate the Asian contribution to airborne particles of anthropogenic origin in western North America, using a time series of samples from a pair of sites upwind and downwind of the San Francisco Bay Area. Our results for airborne Pb at these sites indicate a median value of 29% Asian origin, based on mixing relations between distinct regional sample groups. This trans-Pacific Pb is present in small quantities but serves as a tracer for airborne particles within the growing Asian industrial plume. We then applied this analysis to archived samples from urban sites in central California. Taken together, our results suggest that the analysis of Pb isotopes can reveal the distribution of airborne particles affected by Asian industrial pollution at urban sites in northern California. Under suitable circumstances, this analysis can improve understanding of the global transport of pollution, independent of transport models. PMID- 21033736 TI - Tacticity control in the synthesis of poly(lactic acid) polymer stars with dipentaerythritol cores. AB - The synthesis of a family of polymer stars with arms of varied tacticities is discussed. The effect of polymer tacticity on the physical properties of these polymer stars is presented. Dipentaerythritol cores support six poly(lactic acid) (PLA) arms. Lewis acidic tin and aluminum catalysts control the polymerization to afford polymer stars of variable tacticity. The analysis of these polymers by NMR spectroscopy, thermogravimetric analysis, powder X-ray diffraction, and differential scanning calorimetry reveals the effects of tacticity control on the physical properties of the polymer stars. Preliminary decomposition studies suggest that the biodegradation profile of a polymer star may also be tuned by stereochemical control. This is the first systematic altering of tacticity in PLA polymer stars, showing that polymer tacticity can have a great impact on star properties. PMID- 21033737 TI - Design of vanadium complex catalysts for precise olefin polymerization. PMID- 21033738 TI - Combined influence of substrate stiffness and surface topography on the antiadhesive properties of Acr-sP(EO-stat-PO) hydrogels. AB - Biomaterials that prevent nonspecific protein adsorption and cell adhesion are of high relevance for diverse applications in tissue engineering and diagnostics. One of the most widely applied materials for this purpose is Poly(ethylene glycol) (PEG). We have investigated how micrometer line topography and substrate elasticity act upon the antiadhesive properties of PEG-based hydrogels. In our studies we apply bulk hydrogel cross-linked from star-shaped poly(ethylene oxide stat-propylene oxide) macromonomers. Substrate surfaces were topographically patterned via replica molding. Additionally, the mechanical properties were altered by variations in the cross-linking density. Surface patterns with dimensions in the range of the cells' own size, namely 10 MUm wide grooves, induced significant cell adhesion and spreading on the Acr-sP(EO-stat-PO) hydrogels. In contrast, there was only little adhesion to smaller and larger pattern sizes and no adhesion at all on the smooth substrates, regardless the rigidity of the gel. The effect of varied substrate stiffness on cell behavior was only manifest in combination with topography. Softer substrates with line patterns lead to significantly higher cell adhesion and spreading than stiff substrates. We conclude that the physical and mechanical surface characteristics can eliminate the nonadhesive properties of PEG-based hydrogels to a large extent. This has to be taken into account when designing surfaces for biomedical application such as scaffolds for tissue engineering which rely on the inertness of PEG. PMID- 21033739 TI - Docking validation resources: protein family and ligand flexibility experiments. AB - A database consisting of 780 ligand-receptor complexes, termed SB2010, has been derived from the Protein Databank to evaluate the accuracy of docking protocols for regenerating bound ligand conformations. The goal is to provide easily accessible community resources for development of improved procedures to aid virtual screening for ligands with a wide range of flexibilities. Three core experiments using the program DOCK, which employ rigid (RGD), fixed anchor (FAD), and flexible (FLX) protocols, were used to gauge performance by several different metrics: (1) global results, (2) ligand flexibility, (3) protein family, and (4) cross-docking. Global spectrum plots of successes and failures vs rmsd reveal well-defined inflection regions, which suggest the commonly used 2 A criteria is a reasonable choice for defining success. Across all 780 systems, success tracks with the relative difficulty of the calculations: RGD (82.3%) > FAD (78.1%) > FLX (63.8%). In general, failures due to scoring strongly outweigh those due to sampling. Subsets of SB2010 grouped by ligand flexibility (7-or-less, 8-to-15, and 15-plus rotatable bonds) reveal that success degrades linearly for FAD and FLX protocols, in contrast to RGD, which remains constant. Despite the challenges associated with FLX anchor orientation and on-the-fly flexible growth, success rates for the 7-or-less (74.5%) and, in particular, the 8-to-15 (55.2%) subset are encouraging. Poorer results for the very flexible 15-plus set (39.3%) indicate substantial room for improvement. Family-based success appears largely independent of ligand flexibility, suggesting a strong dependence on the binding site environment. For example, zinc-containing proteins are generally problematic, despite moderately flexible ligands. Finally, representative cross docking examples, for carbonic anhydrase, thermolysin, and neuraminidase families, show the utility of family-based analysis for rapid identification of particularly good or bad docking trends, and the type of failures involved (scoring/sampling), which will likely be of interest to researchers making specific receptor choices for virtual screening. SB2010 is available for download at http://rizzolab.org . PMID- 21033740 TI - Rh(I)-catalyzed direct arylation of azines. AB - The Rh(I)-catalyzed direct arylation of azines has been developed. Quinolines and 2-substituted pyridines couple with aryl bromides to efficiently afford ortho arylated azine products using the commercially available and air-stable catalyst [RhCl(CO)2]2. Electron-deficient and electron-rich aromatic bromides couple in good yields, and hydroxyl, chloro, fluoro, trifluoromethyl, ether, and ketone functionalities are compatible with the reaction conditions. Aroyl chlorides also serve as effective azine coupling partners to give ortho-arylation products via a decarbonylation pathway. PMID- 21033741 TI - Structural determination of a key exopolysaccharide in mixed culture aerobic sludge granules using NMR spectroscopy. AB - Nuclear magnetic resonance (NMR) techniques were used to elucidate the structure of an exopolysaccharide material previously revealed to be important in formation of aerobic granules. The 1D NMR spectral data acquired showed that this gel forming polysaccharide was a major component of granular EPS, while 1D and 2D NMR spectra showed it consisted of eight sugar residues. These were assigned as alpha galactose, alpha-rhamnose, 2-acetoamido-2-deoxy-alpha-galactopyranuronic acid, beta-mannose, beta-galactose, beta-glucuronate, beta-glucosamine, and N-acetyl beta-galactosamine. With the exception of 2-acetoamido-2-deoxy-alpha galactopyranuronic acid, a highly unusual sugar, their presence was confirmed with high-performance anion-exchange chromatography with pulsed amperometric detection (HPAEC-PAD). Carbon and proton shifts were assigned for each sugar. Heteronuclear multiple bond correlation (HMBC) and nuclear Overhauser enhancement spectroscopy (NOESY) were used to identify linkage sites between individual sugar residues. This gel-forming exopolysaccharide appeared to be a highly complex single heteropolysaccharide with a repeat sequence of alpha-galactose, beta mannose, beta-glucosamine, N-acetyl-beta-galactosamine, and 2-acetoamido-2-deoxy alpha-galactopyranuronic acid. It has a disaccharide branch of beta-galactose and beta-glucuronic acid attached to 2-acetoamido-2-deoxy-alpha-galactopyranuronic acid and an alpha-rhamnose branch attached to alpha-galactose. PMID- 21033743 TI - Tandem nucleophilic addition-intramolecular aza-Michael reaction: facile synthesis of chiral fluorinated isoindolines. AB - A highly stereoselective synthesis of fluorinated 1,3-disubstituted isoindolines is described. To this end, a tandem reaction consisting of a diastereoselective addition of fluorinated nucleophiles to Ellman's N-(tert-butanesulfinyl)imines followed by an intramolecular aza-Michael reaction has been developed. This strategy allows for the construction of isoindolines bearing several degrees of fluorination (mono-, di-, or trifluoromethyl as well as heavier fluorinated groups). In the majority of all cases, the products are formed as single isomers. PMID- 21033744 TI - Adsorption of transgenic insecticidal Cry1Ab protein to SiO2. 2. Patch-controlled electrostatic attraction. AB - Adsorption governs the fate of Cry proteins from genetically modified Bt crops in soils. The effect of ionic strength (I) on the adsorption of Cry1Ab (isoelectric point IEP(Cry1Ab) ~ 6) to negatively charged quartz (SiO(2)) and positively charged poly-L-lysine (PLL) was investigated at pH 5 to 8, using quartz crystal microbalance with dissipation monitoring and optical waveguide lightmode spectroscopy. Cry1Ab adsorbed via positively and negatively charged surface patches to SiO(2) and PLL, respectively. This patch controlled electrostatic attraction (PCEA) explains the observed increase in Cry1Ab adsorption to sorbents that carried the same net charge as the protein (SiO(2) at pH > IEP(Cry1Ab) and PLL at pH < IEP(Cry1Ab)) with decreasing I. In contrast, the adsorption of two reference proteins, BSA and HEWL, with different adsorption mechanism, were little affected by similar changes of I. Consistent with PCEA, Cry1Ab desorption from SiO(2) at pH > IEP(Cry1Ab) increased with increasing I and pH. Weak Cry1Ab SiO(2) PCEA above pH 7 resulted in reversible, concentration dependent adsorption. Solution depletion experiments showed that PCEA also governed Cry1Ab adsorption to SiO(2) particles at environmentally relevant concentrations (a few ng mL(-1)). These results imply that models describing Cry1Ab adsorption to charged surfaces in soils need to account for the nonuniform surface charge distribution of the protein. PMID- 21033745 TI - Adsorption of transgenic insecticidal Cry1Ab protein to SiO2. 1. Forces driving adsorption. AB - Genetically modified Bt crops express insecticidal Cry proteins (Bt toxins) that may enter agricultural soils. A mechanistic understanding of Cry protein adsorption to soils is critical for risk assessment, as this process governs Cry protein fate and bioavailability. We used quartz crystal microbalance and optical waveguide lightmode spectroscopy to elucidate the driving forces of the adsorption of monomeric Cry1Ab to negatively charged quartz (SiO(2)) and positively charged poly-L-lysine (PLL) at pH 5-8 and constant ionic strength of 50 mM (NaCl). Bovine serum albumin and hen egg white lysozyme were used as reference proteins because of their known adsorption behavior. Electrostatics governed Cry1Ab adsorption; as pH increased above the isoelectric point of Cry1Ab, the initial rate and the extent of adsorption decreased on SiO(2) and increased on PLL. Reversible adsorption to SiO(2) suggested weak Cry1Ab-SiO(2) electrostatic interactions and no irreversible conformational changes of Cry1Ab at the surface. High conformational stability of Cry1Ab was further supported by supply rate-independent extent of adsorption of Cry1Ab to apolar gold. Some evidence is presented that the nonuniform surface charge distribution of Cry1Ab resulted in patch-controlled electrostatic attraction with sorbents that carried the same net charge as Cry1Ab. A more detailed discussion of this mechanism is given in a companion paper. PMID- 21033746 TI - Granule structure and distribution of allomorphs in C-type high-amylose rice starch granule modified by antisense RNA inhibition of starch branching enzyme. AB - C-type starch, which is a combination of both A-type and B-type crystal starch, is usually found in legumes and rhizomes. We have developed a high-amylose transgenic line of rice (TRS) by antisense RNA inhibition of starch branching enzymes. The starch in the endosperm of this TRS was identified as typical C-type crystalline starch, but its fine granular structure and allomorph distribution remained unclear. In this study, we conducted morphological and spectroscopic studies on this TRS starch during acid hydrolysis to determine the distribution of A- and B-type allomorphs. The morphology of starch granules after various durations of acid hydrolysis was compared by optical microscopy, scanning electron microscopy, and transmission electron microscopy. The results showed that amorphous regions were located at the center part of TRS starch subgranules. During acid hydrolysis, starch was degraded from the interior of the subgranule to the outer surface, while the peripheral part of the subgranules and the surrounding band of the starch granule were highly resistant to acid hydrolysis. The spectroscopic changes detected by X-ray powder diffraction, 13C cross polarization magic-angle spinning NMR, and attenuated total reflectance Fourier transform infrared showed that the A-type allomorph was hydrolyzed more rapidly than the B-type, and that the X-ray diffraction profile gradually changed from a native C-type to a CB-type with increasing hydrolysis time. Our results showed that, in TRS starch, the A-type allomorph was located around the amorphous region, and was surrounded by the B-type allomorph located in the peripheral region of the subgranules and the surrounding band of the starch granule. Thus, the positions of A- and B-type allomorphs in the TRS C-type starch granule differ markedly from those in C-type legume and rhizome starch. PMID- 21033747 TI - A G3 study of the structure of carbon-nitrogen nanoclusters. AB - Possible structures of the carbon-nitrogen clusters of the form C(m)N(n) (m = 1 4, n = 1-4, m + n = 2-5) were predicted for the neutral, anion, and cation species in the singlet, doublet, and triplet states, whenever appropriate. The calculations were performed at the G3, MP2(fc)/6-311+G*, and B3LYP/6-311+G* levels of theory. Several molecular properties related to the experimental data- such as the electronic energy, equilibrium geometry, binding energy, HOMO-LUMO gap (HLG), and spin contamination --were calculated. In addition the vertical electron attachment, the adiabatic electron affinity, and vertical ionization energy, of the neutral clusters were calculated. Most of the predicted lowest energy structures were linear, whereas bent structures became more stable with the increase of the cluster size and increase of the number of the N atoms. In most of the predicted lowest energy structures, the N atom prefers the terminal position with acetylenic bond. The calculated BE of the predicted clusters increases with the increase of the cluster size for the neutral and cation clusters but decreases with the increase of the cluster size for the anion clusters. The predicted clusters are characterized by high HLG of about 11 eV on the average, with that of the anion clusters is smaller than that for the neutral and cation clusters. It is concluded then that the anion clusters are less stable than the corresponding neutral and cation clusters. Finally, the N(2) loss reaction is treated. PMID- 21033748 TI - A bismuth(III)-catalyzed Friedel-Crafts cyclization and stereocontrolled organocatalytic approach to (-)-platensimycin. AB - A high yielding route to the (-)-platensimycin core is communicated. This entailed the discovery of Bi(OTf)(3) to catalyze a Friedel-Crafts cyclization of a free lactol, supplemented by LiClO(4) to suppress the Lewis basicity of the sulfonate group. After TBAF-promoted cyclodearomatization, a diastereoselective conjugate reduction of a dienone was achieved by adopting amine-based organocatalytic rationales to reverse the inherent steric control of the substrate. PMID- 21033749 TI - Synthesis of 2-pyridones and iminoesters via Rh(III)-catalyzed oxidative coupling between acrylamides and alkynes. AB - Catalytic oxidative coupling between acrylamides and alkynes was achieved using 0.5 mol % loading of [RhCp*Cl(2)](2) with Cu(OAc)(2) as an oxidant. 2-Pyridones, iminoesters, and substituted indoles could be obtained as a result of the electronic and steric effects of the substituents in the acrylamides. PMID- 21033751 TI - Impact of molecular conformation on barriers to internal methyl rotation: the rotational spectrum of m-methylbenzaldehyde. AB - The ground state spectrum of m-methylbenzaldehyde (m-MBA) was measured with a chirped-pulse Fourier transform microwave (CP-FTMW) spectrometer. The methyl rotor on m-MBA introduces an internal rotation barrier, which leads to splitting of the torsional energy level degeneracy into A and E states. Ab initio calculations predict a low torsional barrier for both the O-cis and O-trans conformers, resulting in a large doublet splitting up to several gigahertz in the frequency spectrum. The rotational constants, distortion terms, and V(3) values for both species have been determined from the ground state rotational spectrum using the BELGI-C(s) fitting program. There are significant differences in the torsional potential for the O-cis and O-trans m-MBA conformers. Molecular orbitals and resonance structures for each conformer are analyzed to understand the difference in torsional barrier height as well as the irregular shape of the O-trans torsional potential. PMID- 21033750 TI - Indium-tin oxide coated microfabricated device for the injection of a single cell into a fused silica capillary for chemical cytometry. AB - A microfabricated device is described for the capture and injection of a single mammalian cell into a fused silica capillary for subsequent analysis by chemical cytometry. The device consists of a 500 MUm diameter well made from polydimethylsiloxane on an indium-tin oxide coated microscope slide. The bottom of the well contains a 2 MUm high aperture, which was designed to block passage of cells. A cellular suspension was allowed to settle on the device, and aspiration through the aperture was used to trap a single NG-108 cell. Untrapped cells were washed from the device, and a 150 MUm outer diameter and 50 MUm inner diameter capillary was placed in the well. To inject a cell, voltage was applied to the indium-tin oxide while simultaneously applying vacuum at the distal end of the capillary. PMID- 21033752 TI - High resolution millimeter-wave spectroscopy of vinyltellurol. AB - The millimeter-wave rotational spectrum of vinyltellurol has been recorded and assigned for the first time. To support the spectrum assignment, high level ab initio calculations have been carried out. Geometries, total electronic energies, and harmonic vibrational frequencies have been determined at the MP2 level. A small-core relativistic pseudopotential basis set (cc-pVTZ-PP) was employed to describe the tellurium atom. Two stable conformers, synperiplanar (sp) and anticlinal (ac), have been identified. The sp conformer is planar with a small negative inertia defect of -0.025 u A(2). The ac conformer was found to be nonplanar with a C-C-Te-H dihedral angle of about 140 degrees from sp. This conformer exhibits a large amplitude motion associated with the torsion about the C-Te bond. The barrier to internal rotation is about 1 kJ/mol, according to the theoretical calculations. For the ac conformation, a torsional potential function consisting of quartic and quadratic terms of the torsional angle has been partially determined from the observed rotational constants. PMID- 21033754 TI - Experimental and chemical kinetic modeling study of 3-pentanone oxidation. AB - Shock tube ignition delay times have been measured for 3-pentanone at a reflected shock pressure of 1 atm (+/-2%), in the temperature range 1250-1850 K, at equivalence ratios of 0.5-2.0 for O(2) mixtures in argon with fuel concentrations varying from 0.875 to 1.3125%. Laminar flame speeds have also been measured at an initial pressure of 1 atm over an equivalence ratio range. Complementary to previous studies [Pichon S., Black, G., Chaumeix, N., Yahyaoui, M., Simmie, J. M., Curran, H. J., Donohue, R. Combust. Flame, 2009, 156, 494-504; Serinyel, Z.; Black, G.; Curran, H. J.; Simmie, J. M. Combustion Sci. Tech., 2010, 182, 574 587], laminar flame speeds of 2-butanone have also been measured, and relative reactivities of these ketones have been compared and discussed. A chemical kinetic submechanism describing the oxidation of 3-pentanone has been developed and detailed in this paper; rate constants for unimolecular fuel decomposition reactions have been treated for falloff in pressure with nine-parameter fits using the Troe Formulism. Both compounds treated in this work may be used as fuel tracers, thus further ignition delay time measurements have been carried out by adding 3-pentanone to n-heptane in order to test the effect of the blend on ignition delay timing. It was found that the autoignition characteristics of n heptane remained unaffected in the presence of 15% 3-pentanone in the fuel, consistent with results obtained using acetone and 2-butanone [Pichon S., Black, G., Chaumeix, N., Yahyaoui, M., Simmie, J. M., Curran, H. J., Donohue, R. Combust. Flame, 2009, 156, 494-504; Serinyel, Z.; Black, G.; Curran, H. J.; Simmie, J. M. Combustion Sci. Tech., 2010, 182, 574-587]. PMID- 21033753 TI - Biomimetic membranes with aqueous nano channels but without proteins: impedance of impregnated cellulose ester filters. AB - Earlier we have shown that many important properties of ionic aqueous channels in biological membranes can be imitated using simple biomimetic membranes. These membranes are composed of mixed cellulose ester-based filters, impregnated with isopropyl myristate or other esters of fatty acids, and can be used for high throughput drug screening. If the membrane separates two aqueous solutions, combination of relatively hydrophilic polymer support with immobilized carboxylic groups results in the formation of thin aqueous layers covering inner surface of the pores, while the pore volume is filled by lipid-like substances. Because of these aqueous layers biomimetic membranes even without proteins have a cation/anion ion selectivity and specific (per unit of thickness) electrical properties, which are similar to typical properties of biological membranes. Here we describe frequency-dependent impedance of the isopropyl myristate-impregnated biomimetic membranes in the 4-electrode arrangement and present the results as Bode and Nyquist diagrams. When the membranes are placed in deionized water, it is possible to observe three different dispersion processes in the frequency range 0.1 Hz to 30 kHz. Only one dispersion is observed in 5 mM KH(2)PO(4) solution. It is suggested that these three dispersion features are determined by (a) conductivity in aqueous structures/channels, formed near the internal walls of the filter pores at high frequencies, (b) dielectric properties of the whole membrane at medium frequencies, determined by polymer support, aqueous layers and impregnating oil, and, finally, (c) by the processes in hydrated liquid crystal structures formed in pores by impregnating oil in contact with water at low frequencies. PMID- 21033755 TI - Pd(OAc)(2)-catalyzed oxidative C-H/C-H cross-coupling of electron-deficient polyfluoroarenes with simple arenes. AB - Pd(OAc)(2)-catalyzed intermolecular C-H/C-H cross-coupling reactions between electron-deficient polyfluoroarenes and simple arenes for the synthesis of fluorinated biaryls have been developed. Deuterium-labeling experiments suggested that C-H bond cleavage of the simple arenes rather than the polyfluoroarenes is involved in the rate-limiting step. PMID- 21033756 TI - Organic Zener diodes: tunneling across the gap in organic semiconductor materials. AB - Organic Zener diodes with a precisely adjustable reverse breakdown from -3 to -15 V without any influence on the forward current-voltage curve are realized. This is accomplished by controlling the width of the charge depletion zone in a pin diode with an accuracy of one nanometer independently of the doping concentration and the thickness of the intrinsic layer. The breakdown effect with its exponential current voltage behavior and a weak temperature dependence is explained by a tunneling mechanism across the highest occupied molecular orbital lowest unoccupied molecular orbital gap of neighboring molecules. The experimental data are confirmed by a minimal Hamiltonian model approach, including coherent tunneling and incoherent hopping processes as possible charge transport pathways through the effective device region. PMID- 21033757 TI - GaN nanowire functionalized with atomic layer deposition techniques for enhanced immobilization of biomolecules. AB - We report the use of atomic layer deposition (ALD) coating as a nanobiosensor functionalization strategy for enhanced surface immobilization that may enable higher detection sensitivity. Three kinds of ALD coating films, Al(2)O(3), TiO(2), and SiO(2), were grown on the gallium nitride nanowire (GaN NW) surfaces and characterized with high-resolution transmission electron microscopy (HRTEM) and vacuum Fourier transform infrared spectroscopy (FTIR). Results from HRTEM showed that the thicknesses of ALD-Al(2)O(3), ALD-TiO(2) and ALD-SiO(2) coatings were 4-5 nm, 5-6 nm, and 12-14 nm, respectively. Results from FTIR showed that the OH contents of these coatings were, respectively, ~6.9, ~7.4, and ~9.3 times that of piranha-treated GaN NW. Furthermore, to compare protein attachments on the different surfaces, poly(ethylene glycol) (PEG)-biotin was grafted on the OH functionalized GaN NW surfaces through active Si-Cl functional groups. Streptavidin protein molecules were then attached to the biotin ends via specific binding. The immobilized streptavidin molecules were examined with scanning electron microscopy, HRTEM, and fluorescent imaging. Results from HRTEM and energy-dispersive X-ray revealed that the nitrogen concentrations on the three ALD coatings were significantly higher than that on the piranha-treated surface. Results from fluorescent imaging further showed that the protein attachments on the Al(2)O(3), TiO(2), and SiO(2) ALD coatings were, respectively, 6.4, 7.8, and 9.8 times that of piranha-treated surface. This study demonstrates that ALD coating can be used as a functionalization strategy for nanobiosensors because it is capable of creating functional groups with much higher density compared to widely used acid modifications, and among the three ALD coatings, ALD-SiO(2) yielded the most promising results in OH content and protein attachment. PMID- 21033758 TI - Investigation of macroscopic interfacial dynamics between clathrate hydrates and surfactant solutions. AB - Macroscopic interfacial interactions between cyclopentane (CP) hydrates and various surfactants droplets are examined in a CP/n-decane oil mixture. Initial contact force and subsequent z-axis dependent retraction force are measured utilizing a high-resolution microbalance integrated with a micrometer-precision stage. The resulting retraction force is utilized to determine the overall adhesion energy of the system. In addition, interfacial tensions and contact angles of the system are examined to further understand the effect of surface active agents and substrates on the initial contact and retraction forces. PMID- 21033759 TI - Microfluidic preparation of dual stimuli-responsive microparticles and light directed clustering. AB - We present a simple fabrication of photo- and thermoresponsive microparticles with a narrow size distribution in the PDMS-based microfluidic device. The monodisperse water-in-oil (W/O) droplets of poly(N-isopropylacrylamide-co spironaphthoxazine methacryloyl) (PNIPA-SPO) were formed at the T-junction channel of the device by adjusting the flow conditions of two immiscible solutions. Subsequently, the droplets were polymerized downstream of the channel under 365 nm UV irradiation in the presence of 2,2'-diethoxyacetophenone (DEAP, photoinitiator) and N,N'-methylenebisacrylamide (MBA, monomer and cross-linker). Being photosensitive, the polymerized microparticles progressively change their color when subjected to UV-vis irradiation. Above the LCST of the copolymer, the microparticles exhibited volume shrinkage accompanied by color deterioration. In addition, the UV light-driven clustering of the PNIPA-SPO copolymer was observed within the W/O droplet in the absence of photoinitiator, which contributed to variable microstructures from Janus to acorn-like and snowman-like morphologies. This work is the first attempt to unveil the photocontrolled asymmetric particle morphology by using the photoresponsive polymer. PMID- 21033760 TI - Molecular dynamics simulations of grafted layers of bottle-brush polyelectrolytes. AB - Using molecular dynamics simulations, we study the effect of the brush grafting density and degree of polymerization of the side chains on conformations of brush layers made of charged bottle-brush macromolecules. The thickness of the brush layer first decreases with increasing brush grafting density; then, it saturates and remains constant in the wide interval of the brush grafting densities. The brush layers consisting of the bottle-brush macromolecules with longer side chains have a larger layer thickness. The elongation of the side chains of the bottle-brush macromolecules decreases with increasing brush grafting density. This contraction of the side chains is due to counterion condensation inside the volume occupied by bottle-brushes. Our simulations showed that counterion condensation is a multiscale process reflecting different symmetries of the bottle-brush layer. PMID- 21033761 TI - Two-dimensional molecular organization of pyridinecarboxylic acids adsorbed on graphite. AB - Pyridinecarboxylic acids 3-9 are adsorbed from solution onto graphite to produce well-ordered adlayers that can be imaged by scanning tunneling microscopy. Hydrogen bonds involving the carboxyl groups and the nitrogen atom of the pyridyl ring play key roles in controlling the observed two-dimensional (2D) organization. Pyridinecarboxylic acids have a strong tendency to associate to form hydrogen-bonded chains and cyclic oligomers, which then pack to produce sheets. The preference for sheets ensures that molecular organization in 2D and 3D typically shows a significant degree of homology. Together, our observations highlight the potential of engineering similarly ordered 2D and 3D structures built from simple compounds that combine an inherent affinity for surfaces with an ability to engage in strong coplanar intermolecular interactions. PMID- 21033762 TI - Reductive openings of benzylidene acetals revisited: a mechanistic scheme for regio- and stereoselectivity. AB - Despite the importance of regioselective reductive openings of cyclic acetals, mechanistic details are scarce. In this study 4,6-O-benzylidene acetals were used as model compounds for deciphering the mechanism of regioselective openings using a variety of reducing agents. Competitive isotopic studies aiming at primary and secondary isotope effects, as well as an electron-deficient substrate, were used to evaluate stereo- and regioselectivity. We show that there are three distinctly different mechanistic pathways. In nonpolar solvents, such as toluene, the acetal is activated by the very reactive naked Lewis acid to give a fully developed oxocarbenium ion that is then reduced by the borane, with low stereoselectivity. In THF the reactivity of the Lewis acid is moderated by complex formation with the solvent. These reactions are thus much slower and proceed through an intimate ion pair and thereby show high stereoselectivities. The regioselectivity in these reactions is directed by the interaction between the Lewis acid and the most nucleophilic oxygen of the acetal, thus yielding a free 6-hydroxyl group. Finally, boranes such as BH(3).NMe(3) are activated by Lewis acid, which results in the borane being the most electrophilic species, and consequently the reaction shows inversed regioselectivity to give a free 4-hydroxyl group. These reactions proceed through an oxocarbenium ion and thus show low stereoselectivity. PMID- 21033763 TI - Free-standing membranes via covalent cross-linking of polyelectrolyte multilayers with complementary reactivity. AB - Polyelectrolyte multilayers were prepared by the layer-by-layer (LbL) technique from polyanions bearing aldehyde and polycations with 4-methylpyridinium moieties. The aldol reaction of these complementary reactive groups can be followed by the formation of fluorescent merocyanine dyes, resulting in cross linked, ultrathin polymer films. The efficient stabilization of the polymer films allows for their intact removal from high surface energy supports, such as glass or surface oxidized silicon wafers, by simple treatment with salt solutions, yielding free-standing membranes. Increasing separation of the reactive polycation and polyanion layers with layers of inert polycation and polyanion analogues only gradually prevents the coupling reaction. From this dependence, polyions assembled in consecutive adsorption layers seem to be able to penetrate into as far as three neighboring layers. PMID- 21033764 TI - Ab initio studies on the electronic structure and properties of aluminum hydrides that are analogues of boron hydrides. AB - Although the boron hydrides are well-known in the literature, the aluminum hydride chemistry is limited to very few systems such as AlH(3), its dimer, and its polymeric form. In view of the recent experimental studies on the possible existence of the aluminum hydrides, herein, we have undertaken a systematic study on the electronic structure and properties of these aluminum hydrides. Under this, we have studied different classes of hydrides, viz., closo (Al(n)H(n+2)), nido (Al(n)H(n+4)), and arachno (Al(n)H(n+6)), similar to the boranes. All the aluminum hydrides are found to have exceptionally large highest-occupied molecular orbital-lowest-unoccupied molecular orbital gaps, low electron affinities, large ionization potentials and also large enthalpy and free energy of atomization. In addition, most of the structures are also found to have high symmetries. These exceptional properties can be indicative of the pronounced stability, and hence, it is expected that other aluminum hydride complexes can indeed be observed experimentally. PMID- 21033765 TI - In vitro model on glass surfaces for complex interactions between different types of cells. AB - This report establishes an in vitro model on glass surfaces for patterning multiple types of cells to simulate cell-cell interactions in vivo. The model employs a microfluidic system and poly(ethylene glycol)-terminated oxysilane (PEG oxysilane) to modify glass surfaces in order to resist cell adhesion. The system allows the selective confinement of different types of cells to realize complete confinement, partial confinement, and no confinement of three types of cells on glass surfaces. The model was applied to study intercellular interactions among human umbilical vein endothelial cells (HUVEC), PLA 801 C and PLA801 D cells. PMID- 21033766 TI - Valuing Child Health Utility 9D health states with a young adolescent sample: a feasibility study to compare best-worst scaling discrete-choice experiment, standard gamble and time trade-off methods. AB - QALYs are increasingly being utilized as a health outcome measure to calculate the benefits of new treatments and interventions within cost-utility analyses for economic evaluation. Cost-utility analyses of adolescent-specific treatment programmes are scant in comparison with those reported upon for adults and tend to incorporate the views of clinicians or adults as the main source of preferences. However, it is not clear that the views of adults are in accordance with those of adolescents on this issue. Hence, the treatments and interventions most highly valued by adults may not correspond with those most highly valued by adolescents. Ordinal methods for health state valuation may be more easily understood and interpreted by young adolescent samples than conventional approaches. The availability of young adolescent-specific health state values for the estimation of QALYs will provide new insights into the types of treatment programmes and health services that are most highly valued by young adolescents. The first objective of this study was to assess the feasibility of applying best worst scaling (BWS) discrete-choice experiment (DCE) methods in a young adolescent sample to value health states defined by the Child Health Utility 9D (CHU9D) instrument, a new generic preference-based measure of health-related quality of life developed specifically for application in young people. The second objective was to compare BWS DCE questions (where respondents are asked to indicate the best and worst attribute for each of a number of health states, presented one at a time) with conventional time trade-off (TTO) and standard gamble (SG) questions in terms of ease of understanding and completeness. A feasibility study sample of consenting young adolescent school children (n = 16) aged 11-13 years participated in a face-to-face interview in which they were asked to indicate the best and worst attribute levels from a series of health states defined by the CHU9D, presented one at a time. Participants were also randomly allocated to receive additional conventional TTO or SG questions and prompted to indicate how difficult they found them to complete. The results indicate that participants were able to readily choose 'best' and 'worst' dimension levels in each of the CHU9D health states presented to them and provide justification for their choices. Furthermore, when presented with TTO or SG questions and prompted to make comparisons, participants found the BWS DCE task easier to understand and complete. The results of this feasibility study suggest that BWS DCE methods are potentially more readily understood and interpretable by vulnerable populations (e.g. young adolescents). These findings lend support to the potential application of BWS DCE methods to undertake large-scale health state valuation studies directly with young adolescent population samples. PMID- 21033767 TI - Optimizing therapeutic antibody function: progress with Fc domain engineering. AB - Since the establishment of monoclonal antibody production using hybridoma technology in the mid-1970s, there has been expanding progress and continuous technological improvement in the development of therapeutic antibodies. The initial technological breakthroughs involved reduction of immunogenicity and thus enabled repeated administration. The establishment of chimeric, humanized, and fully human antibodies has led to the great success of several 'second generation' therapeutic antibodies, such as rituximab, trastuzumab, cetuximab, and bevacizumab. However, there still exists an urgent demand for improvement in the efficacy of the current antibody therapeutics, which is not yet fully satisfactory for patients. Based on the current understanding of the clinical mechanisms of several therapeutic antibodies, many now believe that Fc-mediated functions (e.g. antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity, and neonatal Fc receptor [FcRn]-mediated storage) will improve the clinical outcomes of therapeutic antibodies. The present review focuses on the recent progress in the development of 'Fc engineering,' which dramatically improves (and sometimes silences) Fc-mediated functions. These achievements can be classified into two technological approaches: (i) introducing amino acid mutations and (ii) modifying Fc-linked oligosaccharide structures. The effectiveness of multiple third-generation therapeutic antibodies armed with various engineered Fcs is now ready to be tested in clinical trials. PMID- 21033768 TI - Communication: Relationships between Intermolecular potential, thermodynamics, and dynamic scaling in viscous systems. AB - In this communication, we provide a recipe for a consistent relation between dynamic scaling and thermodynamic properties well-grounded by the same intermolecular generalized Lennard-Jones potential, which is derived by using an essentially modified Avramov model within the framework of the "thermodynamic scaling" idea. This relation is experimentally verified very well for supercooled van der Waals liquids, and consequently, it can be a good basis for a proper universal description of molecular dynamics and thermodynamics of viscous systems. PMID- 21033769 TI - A gentler approach to RNEMD: nonisotropic velocity scaling for computing thermal conductivity and shear viscosity. AB - We present a new method for introducing stable nonequilibrium velocity and temperature gradients in molecular dynamics simulations of heterogeneous systems. This method extends earlier reverse nonequilibrium molecular dynamics (RNEMD) methods which use momentum exchange swapping moves. The standard swapping moves can create nonthermal velocity distributions and are difficult to use for interfacial calculations. By using nonisotropic velocity scaling (NIVS) on the molecules in specific regions of a system, it is possible to impose momentum or thermal flux between regions of a simulation while conserving the linear momentum and total energy of the system. To test the method, we have computed the thermal conductivity of model liquid and solid systems as well as the interfacial thermal conductivity of a metal-water interface. We find that the NIVS-RNEMD improves the problematic velocity distributions that develop in other RNEMD methods. PMID- 21033770 TI - Identification of metastable states in peptide's dynamics. AB - A recently developed spectral method for identifying metastable states in Markov chains is used to analyze the conformational dynamics of a four-residue peptide valine-proline-alanine-leucine. We compare our results to empirically defined conformational states and show that the found metastable states correctly reproduce the conformational dynamics of the system. PMID- 21033771 TI - Iterative Monte Carlo formulation of real-time correlation functions. AB - We present an iterative Monte Carlo path integral methodology for evaluating thermally averaged real-time correlation functions. Standard path integral Monte Carlo methods are used to sample paths along the imaginary time contour. Propagation of the density matrix is performed iteratively on a grid composed of the end points of the sampled paths. Minimally oscillatory propagators are constructed using energy filtering techniques. A single propagation yields the values of the correlation function at all intermediate time points. Model calculations suggest that the method yields accurate results over several oscillation periods and the statistical error grows slowly with increasing propagation time. PMID- 21033772 TI - Path integral based calculations of symmetrized time correlation functions. I. AB - In this paper, we examine how and when quantum evolution can be approximated in terms of (generalized) classical dynamics in calculations of correlation functions, with a focus on the symmetrized time correlation function introduced by Schofield. To that end, this function is expressed as a path integral in complex time and written in terms of sum and difference path variables. Taylor series expansion of the path integral's exponent to first and second order in the difference variables leads to two original developments. The first order expansion is used to obtain a simple, path integral based, derivation of the so called Schofield's quantum correction factor. The second order result is employed to show how quantum mechanical delocalization manifests itself in the approximation of the correlation function and hinders, even in the semiclassical limit, the interpretation of the propagators in terms of sets of guiding classical trajectories dressed with appropriate weights. PMID- 21033773 TI - Path integral based calculations of symmetrized time correlation functions. II. AB - Schofield's form of quantum time correlation functions is used as the starting point to derive a computable expression for these quantities. The time composition property of the propagators in complex time is exploited to approximate Schofield's function in terms of a sequence of short time classical propagations interspersed with path integrals that, combined, represent the thermal density of the system. The approximation amounts to linearization of the real time propagators and it becomes exact with increasing number of propagation legs. Within this scheme, the correlation function is interpreted as an expectation value over a probability density defined on the thermal and real path space and calculated by a Monte Carlo algorithm. The performance of the algorithm is tested on a set of benchmark problems. Although the numerical effort required is considerable, we show that the algorithm converges systematically to the exact answer with increasing number of iterations and that it is stable for times longer than those accessible via a brute force, path integral based, calculation of the correlation function. Scaling of the algorithm with dimensionality is also examined and, when the method is combined with commonly used filtering schemes, found to be comparable to that of alternative semiclassical methods. PMID- 21033774 TI - Molecular dynamics at low time resolution. AB - The internal dynamics of macromolecular systems is characterized by widely separated time scales, ranging from fraction of picoseconds to nanoseconds. In ordinary molecular dynamics simulations, the elementary time step Deltat used to integrate the equation of motion needs to be chosen much smaller of the shortest time scale in order not to cut-off physical effects. We show that in systems obeying the overdamped Langevin equation, it is possible to systematically correct for such discretization errors. This is done by analytically averaging out the fast molecular dynamics which occurs at time scales smaller than Deltat, using a renormalization group based technique. Such a procedure gives raise to a time-dependent calculable correction to the diffusion coefficient. The resulting effective Langevin equation describes by construction the same long-time dynamics, but has a lower time resolution power, hence it can be integrated using larger time steps Deltat. We illustrate and validate this method by studying the diffusion of a point-particle in a one-dimensional toy model and the denaturation of a protein. PMID- 21033775 TI - Spin-state splittings, highest-occupied-molecular-orbital and lowest-unoccupied molecular-orbital energies, and chemical hardness. AB - It is known that the exact density functional must give ground-state energies that are piecewise linear as a function of electron number. In this work we prove that this is also true for the lowest-energy excited states of different spin or spatial symmetry. This has three important consequences for chemical applications: the ground state of a molecule must correspond to the state with the maximum highest-occupied-molecular-orbital energy, minimum lowest-unoccupied molecular-orbital energy, and maximum chemical hardness. The beryllium, carbon, and vanadium atoms, as well as the CH(2) and C(3)H(3) molecules are considered as illustrative examples. Our result also directly and rigorously connects the ionization potential and electron affinity to the stability of spin states. PMID- 21033776 TI - The method of Gaussian weighted trajectories. V. On the 1GB procedure for polyatomic processes. AB - In recent years, many chemical reactions have been studied by means of the quasiclassical trajectory (QCT) method within the Gaussian binning (GB) procedure. The latter consists of "quantizing" the final vibrational actions in Bohr spirit by putting strong emphasis on the trajectories reaching the products with vibrational actions close to integer values. A major drawback of this procedure is that if N is the number of product vibrational modes, the amount of trajectories necessary to converge the calculations is ~10(N)*larger than with the standard QCT method. Applying it to polyatomic processes is thus problematic. In a recent paper, however, Czako and Bowman propose to quantize the total vibrational energy instead of the vibrational actions [G. Czako and J. M. Bowman, J. Chem. Phys. 131, 244302 (2009)], a procedure called 1GB here. The calculations are then only ~10 times more time consuming than with the standard QCT method, allowing thereby for considerable numerical saving. In this paper, we propose some theoretical arguments supporting the 1GB procedure and check its validity on model test cases as well as the prototype four-atom reaction OH+D(2)->HOD+D. PMID- 21033777 TI - Ab initio calculations of optical absorption spectra: solution of the Bethe Salpeter equation within density matrix perturbation theory. AB - We describe an ab initio approach to compute the optical absorption spectra of molecules and solids, which is suitable for the study of large systems and gives access to spectra within a wide energy range. In this approach, the quantum Liouville equation is solved iteratively within first order perturbation theory, with a Hamiltonian containing a static self-energy operator. This procedure is equivalent to solving the statically screened Bethe-Salpeter equation. Explicit calculations of single particle excited states and inversion of dielectric matrices are avoided using techniques based on density functional perturbation theory. In this way, full absorption spectra may be obtained with a computational workload comparable to ground state Hartree-Fock calculations. We present results for small molecules, for the spectra of a 1 nm Si cluster in a wide energy range (20 eV), and for a dipeptide exhibiting charge transfer excitations. PMID- 21033779 TI - Frozen density embedding with hybrid functionals. AB - The Kohn-Sham equations with constrained electron density are extended to hybrid exchange-correlation (XC) functionals. We derive the frozen density embedding generalized Kohn-Sham (FDE-GKS) scheme which allows to treat the nonlocal exact exchange in the subsystems. For practical calculations we propose an approximated version of the FDE-GKS in which the nonadditive exchange potential is computed at a semilocal level. The proposed method is applied to compute the ground-state electronic properties of small test systems and selected DNA base pairs. The results of calculations employing the hierarchy of XC functionals BLYP/B3LYP/BHLYP and PBE/PBE0 are presented, in order to analyze the effect of nonlocal exchange contributions, and compared with reference coupled-cluster singles and doubles results. We find that the use of hybrid functionals leads to a significant improvement in the description of ground-state electronic properties of the investigated systems. The semilocal version of the FDE-GKS correctly reproduces the dipole and the electron density distribution of the exact GKS supramolecular system, with errors smaller than the ones obtained using conventional semilocal XC functionals. PMID- 21033778 TI - Strong electron correlation in the decomposition reaction of dioxetanone with implications for firefly bioluminescence. AB - Dioxetanone, a key component of the bioluminescence of firefly luciferin, is itself a chemiluminescent molecule due to two conical intersections on its decomposition reaction surface. While recent calculations of firefly luciferin have employed four electrons in four active orbitals [(4,4)] for the dioxetanone moiety, a study of dioxetanone [F. Liu et al., J. Am. Chem. Soc. 131, 6181 (2009)] indicates that a much larger active space is required. Using a variational calculation of the two-electron reduced-density-matrix (2-RDM) [D. A. Mazziotti, Acc. Chem. Res. 39, 207 (2006)], we present the ground-state potential energy surface as a function of active spaces from (4,4) to (20,17) to determine the number of molecular orbitals required for a correct treatment of the strong electron correlation near the conical intersections. Because the 2-RDM method replaces exponentially scaling diagonalizations with polynomially scaling semidefinite optimizations, we readily computed large (18,15) and (20,17) active spaces that are inaccessible to traditional wave function methods. Convergence of the electron correlation with active-space size was measured with complementary RDM-based metrics, the von Neumann entropy of the one-electron RDM as well as the Frobenius and infinity norms of the cumulant 2-RDM. Results show that the electron correlation is not correctly described until the (14,12) active space with small variations present through the (20,17) space. Specifically, for active spaces smaller than (14,12), we demonstrate that at the first conical intersection, the electron in the sigma(*) orbital of the oxygen-oxygen bond is substantially undercorrelated with the electron of the sigma orbital and overcorrelated with the electron of the carbonyl oxygen's p orbital. Based on these results, we estimate that in contrast to previous treatments, an accurate calculation of the strong electron correlation in firefly luciferin requires an active space of 28 electrons in 25 orbitals, beyond the capacity of traditional multireference wave function methods. PMID- 21033780 TI - Range-dependent adiabatic connections. AB - Recently, we have implemented a scheme for the calculation of the adiabatic connection linking the Kohn-Sham system to the physical, interacting system. This scheme uses a generalized Lieb functional, in which the electronic interaction strength is varied in a simple linear fashion, keeping the potential or the density fixed in the process. In the present work, we generalize this scheme further to accommodate arbitrary two-electron operators, allowing the calculation of adiabatic connections following alternative paths as outlined by Yang [J. Chem. Phys. 109, 10107 (1998)]. Specifically, we examine the error-function and Gaussian-attenuated error-function adiabatic connections. It is shown that while the error-function connection displays some promising features, making it amenable to the possible development of new exchange-correlation functionals by modeling the adiabatic connection integrand, the Gaussian-attenuated error function connection is less promising. We explore the high-density and strong static correlation regimes for two-electron systems. Implications of this work for the utility of range-separated schemes are discussed. PMID- 21033781 TI - Unified interpretation of Hund's first and second rules for 2p and 3p atoms. AB - A unified interpretation of Hund's first and second rules for 2p (C, N, O) and 3p (Si, P, S) atoms is given by Hartree-Fock (HF) and multiconfiguration Hartree Fock (MCHF) methods. Both methods exactly satisfy the virial theorem, in principle, which enables one to analyze individual components of the total energy E(=T+V(en)+V(ee)), where T, V(en), and V(ee) are the kinetic, the electron nucleus attraction, and the electron-electron repulsion energies, respectively. The correct interpretation for each of the two rules can only be achieved under the condition of the virial theorem 2T+V=0 by investigating how V(en) and V(ee) interplay to attain the lower total potential energy V(=V(en)+V(ee)). The stabilization of the more stable states for all the 2p and 3p atoms is ascribed to a greater V(en) that is caused by contraction of the valence orbitals accompanied with slight expansion of the core orbitals. The contraction of the valence orbitals for the two rules is a consequence of reducing the Hartree screening of the nucleus at short interelectronic distances. The reduced screening in the first rule is due to a greater amount of Fermi hole contributions in the state with the highest total spin-angular momentum S. The reduced screening in the second rule is due to the fact that two valence electrons are more likely to be on opposite sides of the nucleus in the state with the highest total orbital-angular momentum L. For each of the two rules, the inclusion of correlation does not qualitatively change the HF interpretation, but HF overestimates the energy difference ?DeltaE? between two levels being compared. The magnitude of the correlation energy is significantly larger for the lower L states than for the higher L states since two valence electrons in the lower L states are less likely to be on opposite sides of the nucleus. The MCHF evaluation of ?DeltaE? is in excellent agreement with experiment. The present HF and MCHF calculations demonstrate the above statements that were originally given by Katriel [Theor. Chem. Acta 23, 309 (1972); 26, 163 (1972)]. We have, for the first time, analyzed the correlation-induced changes in the radial density distribution for the excited LS terms of the 2p and 3p atoms as well as for the ground LS term. PMID- 21033782 TI - N 1s photoelectron angular distributions from fixed-in-space NO2 molecules: stereodynamics and symmetry considerations. AB - Angular distributions of N 1s photoelectrons from fixed-in-space NO(2) molecules have been measured over the energy region of shape resonance and above. A multiple-coincidence velocity-map imaging technique for observation of molecular frame photoelectron angular distributions (MF-PADs) has been extended to nonlinear molecular targets. Density functional theory calculations have also been conducted to elucidate the photoionization dynamics and shape resonance in the N 1s photoionization of NO(2). Results show that the N 1s MF-PADs exhibit strong shape variation as a function of both photoelectron kinetic energy and symmetries of final states, whereas asymmetry parameters of laboratory frame PADs show a local minimum around the shape resonance region and increase monotonically as the photon energy increases. Over the shape resonance, the spatial shape of the photoelectron wave function with b(2)-symmetry closely resembles that of 5b(2)(*) unoccupied molecular orbital of NO(2), although the MF-PAD pattern for b(2)-symmetry does not correspond directly to the 5b(2)(*) orbital shape. At higher kinetic energy of 90 eV, MF-PADs become less structured, but still show a significant dependence on the symmetry of final states. PMID- 21033783 TI - Theoretical study of Al+-RG (RG = He-Rn). AB - We present the results of CCSD(T) calculations on the full set of Al(+)-RG complexes (RG = He-Rn). Potential energy curves are calculated pointwise, employing the full counterpoise correction and basis sets of quadruple-zeta and quintuple-zeta quality, and then extrapolated to the complete basis set limit. Each curve has been employed to calculate rovibrational energy levels, from which spectroscopic parameters have been derived. These are compared to the available experimental data, and it is seen that there is excellent agreement with the values obtained from both Rydberg state extrapolations and high-resolution laser induced fluorescence studies. Finally, we have also used our potentials to calculate transport coefficients for Al(+) moving through a bath of RG. PMID- 21033784 TI - Complete experimental rovibrational eigenenergies of HNC up to 3743 cm(-1) above the ground state. AB - The [H,C,N] system is one of the ideal candidate molecules to test new models aimed to calculate the manifold of the rotational, vibrational, and electronic states of a triatomic molecule. The isomerization reaction HCN?HNC is one of the most important model systems for the study of unimolecular reactions. This paper reports on the experimental characterization of all 1191 eigenenergies up to 3743 cm(-1) relative to the ground state in the HNC part of the potential surface using high temperature hot gas emission spectroscopy. The spectroscopic constants for the first 27 vibrational states including highly excited bending vibrations up to v(2) = 7 are reported. The first 14 rotational perturbations have been identified and the perturbed eigenenergies were determined. The 3200 eigenenergies up to J = 70 for the first 47 vibrational substates are included as supplement to this paper. PMID- 21033785 TI - Ab initio adiabatic and quasidiabatic potential energy surfaces of lowest four electronic states of the H+ + O2 system. AB - Ab initio global adiabatic and quasidiabatic potential energy surfaces of lowest four electronic (1-4 (3)A(")) states of the H(+)+O(2) system have been computed in the Jacobi coordinates (R,r,gamma) using Dunning's cc-pVTZ basis set at the internally contracted multireference (single and double) configuration interaction level of accuracy, which are relevant to the dynamics studies of inelastic vibrational and charge transfer processes observed in the scattering experiments. The computed equilibrium geometry parameters of the bound [HO(2)](+) ion in the ground electronic state and other parameters for the transition state for the isomerization process, HOO(+)?OOH(+) are in good quantitative agreement with those available from the high level ab initio calculations, thus lending credence to the accuracy of the potential energy surfaces. The nonadiabatic couplings between the electronic states have been analyzed in both the adiabatic and quasidiabatic frameworks by computing the nonadiabatic coupling matrix elements and the coupling potentials, respectively. It is inferred that the dynamics of energy transfer processes in the scattering experiments carried out in the range of 9.5-23 eV would involve all the four electronic states. PMID- 21033786 TI - Ab initio characterization of the Mg-HF van der Waals complex. AB - The equilibrium structure and the three-dimensional potential energy surface of the Mg-HF van der Waals complex in its ground electronic state have been determined from accurate ab initio calculations using the coupled-cluster method, CCSD(T), in conjunction with the basis sets of triple- through quintuple-zeta quality. The core-electron correlation, high-order valence-electron correlation, and scalar relativistic effects were investigated. The Mg-HF complex was confirmed to be linear at equilibrium, with a vibrationless dissociation energy (into Mg and HF) D(e) of 280 cm(-1). The vibration-rotation energy levels of two isotopologues, (24)Mg-HF and (24)Mg-DF, were predicted using the variational method. The predicted spectroscopic constants can be useful in a further analysis of high-resolution vibration-rotation spectra of the Mg-HF complex. PMID- 21033787 TI - Quasiclassical trajectory study of the postquenching dynamics of OH A 2Sigma+ by H2/D2 on a global potential energy surface. AB - We report full-dimensional, electronically adiabatic potential energy surfaces (PESs) for the ground state (1A(')) and excited state (2A(')) of OH(3). The PESs are permutationally invariant fits to roughly 23,000 electronic energies (MRCI + Q/aVTZ). Classical trajectory calculations of the postquenching dynamics of OH A (2)Sigma(+) are carried out on the 1A(') PES for H(2) and D(2), at previously identified conical intersections (CoIs) [B. C. Hoffman and D. R. Yarkony, J. Chem. Phys. 113, 10091 (2000)]. The initial momenta are sampled fully and partially microcanonically, corresponding to "adiabatic" and "diabatic" models of the dynamics, respectively. Branching ratios of reactive to nonreactive channels from separate C(2v), C(infinityv), and C(s) symmetries of CoIs are calculated, as are final rovibrational state distributions of OH and H(2) products. The rovibrational distributions of the OH and D(2) products, the D/H-atom translational energy distribution are calculated and compared to experimental ones. Agreement for these observable quantities is good. The branching between reactive and nonreactive quenching is sensitive to the momenta sampling; very good agreement with experiment is obtained using the diabatic sampling but not with the adiabatic sampling. The vibrational state distributions of H(2)O and HOD (although not measured by experiment) are also presented. PMID- 21033788 TI - Collisional quenching of OD A 2Sigma+ by H2: experimental and theoretical studies of the state-resolved OD X 2Pi product distribution and branching fraction. AB - We report joint experimental and theoretical studies of outcomes resulting from the nonreactive quenching of electronically excited OD A (2)Sigma(+) by H(2). The experiments utilize a pump-probe technique to detect the OD X (2)Pi product state distribution under single collision conditions. The OD X (2)Pi products are observed primarily in their lowest vibrational state (v(") = 0) with substantially less population in v(") = 1. The OD X (2)Pi products are generated with a high degree of rotational excitation, peaking at N(") = 21 with an average rotational energy of 4600 cm(-1), and a strong propensity for populating the Pi(A(')) Lambda-doublet component indicative of alignment of the half-filled ppi orbital in the plane of OD rotation. Branching fraction measurements show that the nonreactive channel accounts for less than 20% of quenching outcomes. Complementary classical trajectory calculations of the postquenching dynamics are initiated from representative points along seams of conical intersections between the ground and excited-state potentials of OD(A (2)Sigma(+),X (2)Pi) + H(2). Diabatic modeling of the initial momenta in the dynamical calculations captures the key experimental trends: OD X (2)Pi products released primarily in their ground vibrational state with extensive rotational excitation and a branching ratio that strongly favors reactive quenching. The OD A (2)Sigma(+) + H(2) results are also compared with previous studies on the quenching of OH A (2)Sigma(+) + H(2); the two experimental studies show remarkably similar rotational energy distributions for the OH and OD X (2)Pi radical products. PMID- 21033789 TI - Ab initio investigation of benzene clusters: molecular tailoring approach. AB - An exhaustive study on the clusters of benzene (Bz)(n), n = 2-8, at MP2/6 31++G(**) level of theory is reported. The relative strengths of CH-pi and pi-pi interactions in these aggregates are examined, which eventually govern the pattern of cluster formation. A linear scaling method, viz., molecular tailoring approach (MTA), is efficiently employed for studying the energetics and growth patterns of benzene clusters consisting up to eight benzene (Bz) units. Accuracy of MTA-based calculations is appraised by performing the corresponding standard calculations wherever possible, i.e., up to tetramers. For benzene tetramers, the error introduced in energy is of the order of 0.1 mH (~0.06 kcal/mol). Although for higher clusters the error may build up, further corrections based on many body interaction energy analysis substantially reduce the error in the MTA estimate. This is demonstrated for a prototypical case of benzene hexamer. A systematic way of building up a cluster of n monomers (n-mer) which employs molecular electrostatic potential of an (n-1)-mer is illustrated. The trends obtained using MTA method are essentially identical to those of the standard methods in terms of structure and energy. In summary, this study clearly brings out the possibility of effecting such large calculations, which are not possible conventionally, by the use of MTA without a significant loss of accuracy. PMID- 21033790 TI - Theoretical study of photoinduced ring-opening in furan. AB - The potential energy surfaces (PESs) of the two lowest excited singlet states of furan [correlating with the Rydberg (1)A(2)(3s) and valence (1)B(2)(V) states at the C(2v) ground-state molecular configuration] have been studied in some detail with regard to the photoinduced ring-opening reaction. The surfaces have been characterized in terms of their stationary points and points of minimum energy conical intersections along the ring-opening pathway. The optimization of the geometrical parameters has been performed with the equation of motion coupled cluster singles and doubles method. The ab initio PESs have been modeled by energy grids and Taylor series. The resulting 11-dimensional PESs reproduce the ab initio results to a good accuracy and can be used in dynamical calculations. PMID- 21033791 TI - The electric dipole moment of iridium monofluoride, IrF. AB - The P(5) branch features of the A (3)Phi(4)<-X (3)Phi(4) (1,0) band near 628.2 nm of a molecular beam of iridium monofluoride, (193)IrF, were recorded field free and in the presence of a static electric field. The (193)Ir (I(1)=3/2) and (19)F (I(2)=1/2) hyperfine interactions in the A (3)Phi(4) (upsilon=1) and X (3)Phi(4) (upsilon=0) states were analyzed. The permanent electric dipole moments, MU(el), for the A (3)Phi(4) (upsilon=1) and X (3)Phi(4) (upsilon=0) states were determined to be 1.88(5) and 2.82(6) D, respectively, from the analysis of the observed Stark shifts. A comparison of the electric dipole moments for IrC, IrN, and CoF is presented. PMID- 21033792 TI - Matrix isolation ESR and theoretical studies of metal phosphides. AB - The ZnP, (67)ZnP, CdP, (111)CdP, and (113)CdP radicals have been formed by laser ablation of the metal with GaP pressed into the metal surface, isolated in an inert neon matrix at 4.3 K and their electronic structure was established using electron spin resonance spectroscopy. The following magnetic parameters were determined experimentally for ZnP/(67)ZnP, g(?)=1.9982(2), A(?)(P)=111(6) MHz, A(?)((67)Zn)=160(2) MHz, and D=-29 988(3) MHz and estimates were made for the following ZnP/(67)ZnP magnetic parameters: g(?)=1.9941(2), A(?)(P)=-5(6) MHz, and A(?)((67)Zn)=180(50) MHz. The following magnetic parameters for CdP/(111)CdP/(113)CdP were determined experimentally: g(?)=1.9963(2), A(?)(P)=97(3) MHz, A(?)((111)Cd)=862(3) MHz, and A(?)((113)Cd)=902(3) MHz. Evidence for the formation of the MgP radical was also obtained and an approximate hyperfine coupling constant of A(?)(P)=157(6) MHz was determined. The low-lying electronic states of ZnP and MgP were also investigated using the multiconfigurational self-consistent field technique. Potential energy surfaces, binding energies, optimized bond lengths, energy separations, and dissociation energies have been determined. Both radicals are found to have (4)Sigma(-) ground states with a leading configuration at r(e) of 10sigma(2)11sigma(2)5pi(1)5pi(1)12sigma(1) for ZnP and 7sigma(2)8sigma(2)3pi(1)3pi(1)9sigma(1) for MgP. Significant mixing to this state is calculated for MgP. PMID- 21033793 TI - Global potential energy surfaces for O((3)P) + H2O((1)A1) collisions. AB - Global analytic potential energy surfaces for O((3)P) + H(2)O((1)A(1)) collisions, including the OH + OH hydrogen abstraction and H + OOH hydrogen elimination channels, are presented. Ab initio electronic structure calculations were performed at the CASSCF + MP2 level with an O(4s3p2d1f)/H(3s2p) one electron basis set. Approximately 10(5) geometries were used to fit the three lowest triplet adiabatic states corresponding to the triply degenerate O((3)P) + H(2)O((1)A(1)) reactants. Transition state theory rate constant and total cross section calculations using classical trajectories to collision energies up to 120 kcal mol(-1) (~11 km s(-1) collision velocity) were performed and show good agreement with experimental data. Flux-velocity contour maps are presented at selected energies for H(2)O collisional excitation, OH + OH, and H + OOH channels to further investigate the dynamics, especially the competition and distinct dynamics of the two reactive channels. There are large differences in the contributions of each of the triplet surfaces to the reactive channels, especially at higher energies. The present surfaces should support quantitative modeling of O((3)P) + H(2)O((1)A(1)) collision processes up to ~150 kcal mol( 1). PMID- 21033795 TI - Structures and energetics of helium cluster cations: equilibrium geometries revisited through the genetic algorithm approach. AB - Equilibrium geometries and dissociation energies of He(N)(+) clusters have been calculated for N=3-35 using an extended genetic algorithm approach and a semiempirical model of intracluster interactions [P. J. Knowles, J. N. Murrell, and E. J. Hodge, Mol. Phys. 85, 243 (1995)]. A general aufbau principle is formulated for both ionic cores and neutral solvation shells, and the results are thoroughly compared with other theoretical data available for helium cluster cations in literature. PMID- 21033794 TI - Selective excitation of LI2 by chirped laser pulses with all possible interstate radiative couplings. AB - We have numerically explored the feasibility and the mechanism of population transfer to the excited E (1)Sigma(g) electronic state of Li(2) from the v=0 level of the ground electronic state X (1)Sigma(g) using the A (1)Sigma(u) state as an intermediate. In this system, the use of transform limited pulses with a frequency difference greater than the maximum Rabi frequency does not produce population transfer when all possible radiative couplings are taken into account. We have employed two synchronous pulses far detuned from the allowed transition frequencies, mainly with the lower frequency pulse positively chirped, and both pulses coupling the successive pair of states, X-A and A-E. The adiabaticity of the process has been investigated by a generalized Floquet calculation in the basis of 12 field dressed molecular states, and the results have been compared with those obtained from the full solution of time dependent Schrodinger equation. The conventional representation of the process in terms of three (or four) adiabatic potentials is not valid. It has been found that for cases of almost complete population transfer in full calculations with the conservation of the vibrational quantum number, adiabatic passage is attained with the 12 state Floquet model but not with the six state model. The agreement between the full calculations and the 12 state Floquet calculations is generally good when the transfer is adiabatic. Another characteristic feature of this work is the gaining of control over the vibrational state preparation in the final electronic state by careful tuning of the laser parameters as well as the chirp rate sign. This causes time dependent changes in the adiabatic potentials and nonadiabatic transfers can be made to occur between them. PMID- 21033796 TI - Coherent Rayleigh-Brillouin scattering measurements of bulk viscosity of polar and nonpolar gases, and kinetic theory. AB - We investigate coherent Rayleigh-Brillouin spectroscopy as an efficient process to measure the bulk viscosity of gases at gigahertz frequencies. Scattered spectral distributions are measured using a Fizeau spectrometer. We discuss the statistical error due to the fluctuating mode structure of the used pump laser. Experiments were done for both polar and nonpolar gases and the bulk viscosity was obtained from the spectra using the Tenti S6 model. Results are compared to simple classical kinetic models of molecules with internal degrees of freedom. At the extremely high (gigahertz) frequencies of our experiment, most internal vibrational modes remain frozen and the bulk viscosity is dominated by the rotational degrees of freedom. Our measurements show that the molecular dipole moments have unexpectedly little influence on the bulk viscosity at room temperature and moderate pressure. PMID- 21033797 TI - Diminished cage effect in solid p-H2: Infrared absorption of CH3S observed from photolysis in situ of CH3SH, CH3SCH3, or CH3SSCH3 isolated in p-H2 matrices. AB - We report the infrared absorption spectrum of the methylthio (or thiomethoxy) radical, CH(3)S (X (2)E(3/2)), produced via photodissociation in situ of three precursors CH(3)SH, CH(3)SCH(3), and CH(3)SSCH(3) isolated in solid p-H(2). The common absorption features observed with similar intensity ratios in each experiment are assigned to CH(3)S. The wavenumbers of these features agree satisfactorily with those predicted with a spin-vibronic Hamiltonian accounting for the anharmonic effects and the Jahn-Teller effects to the quartic term [A. V. Marenich and J. E. Boggs, J. Chem. Theory Comput. 1, 1162 (2005)]. In addition to an absorption line at 724.2 cm(-1), corresponding to a transition of 3(1) previously determined to be 727 cm(-1) from fluorescence spectra of gaseous CH(3)S, we identified fundamental transitions 6(1)(a(1)) at 771.1, 6(1)(e) at 1056.6, 5(1)(a(1)) at 1400.0, 4(1)(a(1)) at 2898.4 cm(-1), and several combination and overtone transitions. In contrast, photolysis of CH(3)SSCH(3) isolated in solid Ar produces mainly H(2)CS, CH(3)SH, and CS(2), but no CH(3)S. These results demonstrate the feasibility of using photolysis in situ of precursors isolated in solid p-H(2) to produce free radicals by taking advantage of the diminished cage effect of the matrix. PMID- 21033798 TI - A comprehensive theoretical investigation of the electronic states of Ca2 up to the Ca(4s(2) 1S) + Ca(4s5p 1P) dissociation limit. AB - A theoretical survey of the electronic structure of Ca(2) is presented using two electron pseudopotentials complemented by core-polarization operators on Ca atoms and multireference configuration interaction/quasidegenerate perturbation theory (MRCI/QDPT) treatment of molecular excited states. The spectroscopic constants of 70 electronic states up to 30,000 cm(-1) above the ground state are determined. This implies all Ca(2) states dissociating up to the Ca(4s(2) (1)S) + Ca(4s5p (3,1)P) dissociation limits. All spin states (singlet, triplet, and quintet) are investigated. The work emphasizes the variety of interactions implying singly valence and lowest Rydberg excited states, doubly excited states generated by atom pairs (3)P(4s4p) + (3)P(4s4p), or (3)P(4s4p) + (3)D(4s3d), 4p3d double excitations asymptotically localized on a single-atom. Zwitterionic Ca(+) + Ca(-) configurations are evidenced and shown to induce specific electronic patterns in (1)Sigma(g)(+), (3)Sigma(g)(+), (1)Sigma(u)(+), (3)Sigma(u)(+), (1)Pi(g), (3)Pi(g), (1)Pi(u), and (3)Pi(u) symmetry manifolds. They also provide insight for qualitative features (barriers) found for the lower electronic states already investigated in previous publications by other authors. PMID- 21033799 TI - On the role of dissipation on the Casimir-Polder potential between molecules in dielectric media. AB - An expression for the Casimir-Polder potential between molecules in a homogeneous dispersive and absorptive dielectric medium is derived. The effect of retardation on the interaction energy is discussed by examining the wave-zone and nonretarded limits of the potential. Unlike Lifshitz theory, the interaction energy is not derived from the potential between macroscopic bodies. In this work, a Green function that explicitly accounts for absorption in the medium is obtained. This function leads to possible dissipation effects and presents a near-zone form that vanishes in the limit of nonabsorptive medium. Employing a two-level model, it is shown that the retarded van der Waals dispersion potential in a medium may become repulsive as a consequence of absorption by the medium. It is suggested that the repulsive dispersion force may delay precipitation of nonpolar molecules from a dielectric solvent or even inhibit chemical reaction between them. PMID- 21033800 TI - One- and two-photon spectroscopy of highly excited states of alkali-metal atoms on helium nanodroplets. AB - Alkali-metal atoms captured on the surface of superfluid helium droplets are excited to high energies (~3 eV) by means of pulsed lasers, and their laser induced-fluorescence spectra are recorded. We report on the one-photon excitation of the (n+1)p<-ns transition of K, Rb, and Cs (n=4, 5, and 6, respectively) and on the two-photon one-color excitation of the 5d<-5s transition of Rb. Gated photon-counting measurements are consistent with the relaxation rates of the bare atoms, hence consistent with the reasonable expectation that atoms quickly desorb from the droplet and droplet-induced relaxation need not be invoked. PMID- 21033801 TI - Heat capacity, enthalpy fluctuations, and configurational entropy in broken ergodic systems. AB - A common assumption in the glass science community is that the entropy of a glass can be calculated by integration of measured heat capacity curves through the glass transition. Such integration assumes that glass is an equilibrium material and that the glass transition is a reversible process. However, as a nonequilibrium and nonergodic material, the equations from equilibrium thermodynamics are not directly applicable to the glassy state. Here we investigate the connection between heat capacity and configurational entropy in broken ergodic systems such as glass. We show that it is not possible, in general, to calculate the entropy of a glass from heat capacity curves alone, since additional information must be known related to the details of microscopic fluctuations. Our analysis demonstrates that a time-average formalism is essential to account correctly for the experimentally observed dependence of thermodynamic properties on observation time, e.g., in specific heat spectroscopy. This result serves as experimental and theoretical proof for the nonexistence of residual glass entropy at absolute zero temperature. Example measurements are shown for Corning code 7059 glass. PMID- 21033802 TI - The isotropic-nematic interface of colloidal goethite in an external magnetic field. AB - Polarization microscopy was used to study the behavior around the isotropic nematic interface of colloidal goethite dispersions in a magnetic field. It has been found before that the nematic phase is favored in an external field. In the case of goethite this was also observed; nematic droplets formed inside the isotropic phase and coalesced with the nematic phase. However, the behavior was found to be much richer because of the particle rotation around a certain critical field strength. The simultaneous occurrence of (parallel)nematic (perpendicular)nematic phase separation under the influence of a magnetic field also plays a role here. PMID- 21033803 TI - Hydration dependent studies of highly aligned multilayer lipid membranes by neutron scattering. AB - We investigated molecular motions on a picosecond timescale of 1,2-dimyristoyl-sn glycero-3-phosphocholine (DMPC) model membranes as a function of hydration by using elastic and quasielastic neutron scattering. Two different hydrations corresponding to approximately nine and twelve water molecules per lipid were studied, the latter being the fully hydrated state. In our study, we focused on head group motions by using chain deuterated lipids. Information on in-plane and out-of-plane motions could be extracted by using solid supported DMPC multilayers. Our studies confirm and complete former investigations by Konig et al. [J. Phys. II (France) 2, 1589 (1992)] and Rheinstadter et al. [Phys. Rev. Lett. 101, 248106 (2008)] who described the dynamics of lipid membranes, but did not explore the influence of hydration on the head group dynamics as presented here. From the elastic data, a clear shift of the main phase transition from the P(beta) ripple phase to the L(alpha) liquid phase was observed. Decreasing water content moves the transition temperature to higher temperatures. The quasielastic data permit a closer investigation of the different types of head group motion of the two samples. Two different models are needed to fit the elastic incoherent structure factor and corresponding radii were calculated. The presented data show the strong influence hydration has on the head group mobility of DMPC. PMID- 21033804 TI - A model proton-transfer system in the condensed phase: NH4(+)OOH(-), a crystal with short intermolecular H-bonds. AB - The crystal structure of NH(4)(+)OOH(-) is determined from single-crystal x-ray data obtained at 150 K. The crystal belongs to the space group P2(1)/c and has four molecules in a unit cell. The structure consists of discrete NH(4)(+) and OOH(-) ions. The OOH(-) ions are linked by short hydrogen bonds (2.533 A) to form parallel infinite chains. The ammonium ions form links between these chains (the N?O distances vary from 2.714 to 2.855 A) giving a three-dimensional network. The harmonic IR spectrum and H-bond energies are computed at the Perdew-Burke Ernzerhof (PBE)/6-31G(**) level with periodic boundary conditions. A detailed analysis of the shared (bridging) protons' dynamics is obtained from the CPMD simulations at different temperatures. PBE functional with plane-wave basis set (110 Ry) is used. At 10 K the shared proton sits near the oxygen atom, only a few proton jumps along the chain are detected at 70 K while at 270 K numerous proton jumps exist in the trajectory. The local-minimum structure of the space group Cc is localized. It appears as a result of proton transfer along a chain. This process is endothermic (~2 kJ/mol) and is described as P2(1)/c<->2Cc. The computed IR spectrum at 10 K is close to the harmonic one, the numerous bands appear at 70 K while at 270 K it shows a very broad absorption band that covers frequencies from about 1000 to 3000 cm(-1). The advantages of the NH(4)(+)OOH(-) crystal as a promising model for the experimental and DFT based molecular dynamics simulation studies of proton transfer along the chain are discussed. PMID- 21033805 TI - Prediction of a structural transition in the hard disk fluid. AB - Starting from the second equilibrium equation in the BBGKY hierarchy under the Kirkwood superposition closure, we implement a new method for studying the asymptotic decay of correlations in the hard disk fluid in the high density regime. From our analysis and complementary numerical studies, we find that exponentially damped oscillations can occur only up to a packing fraction eta(*)~0.718, a value that is in substantial agreement with the packing fraction, eta~0.723, believed to characterize the transition from the ordered solid phase to a dense fluid phase, as inferred from Mak's Monte Carlo simulations [Phys. Rev. E 73, 065104 (2006)]. Next, we show that the same method of analysis predicts that the exponential damping of oscillations in the hard sphere fluid becomes impossible when lambda=4npisigma(3)[1+H(1)]>=34.81, where H(1) is the contact value of the correlation function, n is the number density, and sigma is the sphere diameter in exact agreement with the condition, lambda>=34.8, which is first reported in a numerical study of the Kirkwood equation by Kirkwood et al. [J. Chem. Phys. 18, 1040 (1950)]. Finally, we show that our method confirms the absence of any structural transition in hard rods for the entire range of densities below close packing. PMID- 21033806 TI - Polarized Raman spectroscopic study of relaxed high density amorphous ices under pressure. AB - We have made high density amorphous ice (HDA) by the pressure-induced amorphization of hexagonal ice at 77 K and measured the volume change on isobaric heating in a pressure range between 0.1 and 1.5 GPa. The volume of HDA on heating below ~0.35 GPa increases, while the volume of HDA on heating above ~0.35 GPa decreases. The polarized OH-stretching Raman spectra of the relaxed HDAs are compared with that of the unannealed HDA. The relaxed HDAs are prepared at 0.2 GPa at 130 K and 1.5 GPa at 160 K. It is found that the relatively strong totally symmetric OH-stretching vibration mode around 3100 cm(-1) exists in the depolarized reduced Raman spectrum chi(VH)(") of the unannealed HDA and that its intensity rapidly decreases by relaxation. The chi(VH)(") profiles of the relaxed HDA are similar to those of liquid water. These results indicate that the HDA reaches a nearly equilibrium state by annealing and the intrinsic state of HDA relates to a liquid state. The pressure-volume curve of the relaxed HDA at 140 K seems to be smooth in the pressure range below 1.5 GPa. PMID- 21033807 TI - Isotope effects in liquid water by infrared spectroscopy. IV. No free OH groups in liquid water. AB - The presence of free OH (OH not H-bonded) in bulk water is a key element for the determination of its molecular structure. The OH covalent bond infrared (IR) absorption is highly sensitive to the molecular environment. For this reason, IR spectroscopy is used for the determination of free OH. A workable definition of this is obtained with methanol (MeOH) in hexane where minute quantities of free OH are present. These absorb at 3654 cm(-1) (a 27 cm(-1) redshift from the gas position) with a full width at half height of 35 cm(-1). The IR spectrum of water between room temperature and 95 degrees C does not display such a band near 3650 cm(-1). This indicates that we do not see, in the IR spectra, the "free" OH group. From this we conclude that it is not present in liquid water at least down to the 1000 ppm level which is the limit of detectivity of our spectrometer. Other spectroscopic considerations of methanol and water in acetonitrile solutions indicate that weak H-bonds are also not present in liquid water. PMID- 21033808 TI - Molecular quantum control landscapes in von Neumann time-frequency phase space. AB - Recently we introduced the von Neumann representation as a joint time-frequency description for femtosecond laser pulses and suggested its use as a basis for pulse shaping experiments. Here we use the von Neumann basis to represent multidimensional molecular control landscapes, providing insight into the molecular dynamics. We present three kinds of time-frequency phase space scanning procedures based on the von Neumann formalism: variation of intensity, time frequency phase space position, and/or the relative phase of single subpulses. The shaped pulses produced are characterized via Fourier-transform spectral interferometry. Quantum control is demonstrated on the laser dye IR140 elucidating a time-frequency pump-dump mechanism. PMID- 21033809 TI - Electrolytes in a nanometer slab-confinement: ion-specific structure and solvation forces. AB - We study the liquid structure and solvation forces of dense monovalent electrolytes (LiCl, NaCl, CsCl, and NaI) in a nanometer slab-confinement by explicit-water molecular dynamics (MD) simulations, implicit-water Monte Carlo (MC) simulations, and modified Poisson-Boltzmann (PB) theories. In order to consistently coarse-grain and to account for specific hydration effects in the implicit methods, realistic ion-ion and ion-surface pair potentials have been derived from infinite-dilution MD simulations. The electrolyte structure calculated from MC simulations is in good agreement with the corresponding MD simulations, thereby validating the coarse-graining approach. The agreement improves if a realistic, MD-derived dielectric constant is employed, which partially corrects for (water-mediated) many-body effects. Further analysis of the ionic structure and solvation pressure demonstrates that nonlocal extensions to PB (NPB) perform well for a wide parameter range when compared to MC simulations, whereas all local extensions mostly fail. A Barker-Henderson mapping of the ions onto a charged, asymmetric, and nonadditive binary hard-sphere mixture shows that the strength of structural correlations is strongly related to the magnitude and sign of the salt-specific nonadditivity. Furthermore, a grand canonical NPB analysis shows that the Donnan effect is dominated by steric correlations, whereas solvation forces and overcharging effects are mainly governed by ion-surface interactions. However, steric corrections to solvation forces are strongly repulsive for high concentrations and low surface charges, while overcharging can also be triggered by steric interactions in strongly correlated systems. Generally, we find that ion-surface and ion-ion correlations are strongly coupled and that coarse-grained methods should include both, the latter nonlocally and nonadditive (as given by our specific ionic diameters), when studying electrolytes in highly inhomogeneous situations. PMID- 21033810 TI - Vibrational dynamics, intermolecular interactions, and compound formation in GeH4 H2 under pressure. AB - Optical microscopy, spectroscopic and x-ray diffraction studies at high-pressure are used to investigate intermolecular interactions in binary mixtures of germane (GeH(4)) + hydrogen (H(2)). The measurements reveal the formation of a new molecular compound, with the approximate stoichiometry GeH(4)(H(2))(2), when the constituents are compressed above 7.5 GPa. Raman and infrared spectroscopic measurements show multiple H(2) vibrons substantially softened from bulk solid hydrogen. With increasing pressure, the frequencies of several Raman and infrared H(2) vibrons decrease, indicating anomalous attractive interaction for closed shell, nonpolar molecules. Synchrotron powder x-ray diffraction measurements show that the compound has a structure based on face-centered cubic (fcc) with GeH(4) molecules occupying fcc sites and H(2) molecules likely distributed between O(h) and T(d) sites. Above ca. 17 GPa, GeH(4) molecules in the compound become unstable with respect to decomposition products (Ge + H(2)), however, the compound can be preserved metastably to ca. 27 GPa for time-scales of the order of several hours. PMID- 21033811 TI - Deformation-induced accelerated dynamics in polymer glasses. AB - Molecular dynamics simulations are used to investigate the effects of deformation on the segmental dynamics in an aging polymer glass. Individual particle trajectories are decomposed into a series of discontinuous hops, from which we obtain the full distribution of relaxation times and displacements under three deformation protocols: step stress (creep), step strain, and constant strain rate deformation. As in experiments, the dynamics can be accelerated by several orders of magnitude during deformation, and the history dependence is entirely erased during yield (mechanical rejuvenation). Aging can be explained as a result of the long tails in the relaxation time distribution of the glass, and similarly, mechanical rejuvenation is understood through the observed narrowing of this distribution during yield. Although the relaxation time distributions under deformation are highly protocol specific, in each case they may be described by a universal acceleration factor that depends only on the strain. PMID- 21033812 TI - Femtosecond midinfrared study of aggregation behavior in aqueous solutions of amphiphilic molecules. AB - We study the spectral and orientational dynamics of HDO molecules in aqueous solutions of different concentrations of tertiary butyl alcohol (TBA) and trimethylamine-N-oxide (TMAO). The spectral dynamics is investigated with femtosecond two-dimensional infrared spectroscopy of the O-H stretch vibration of HDO:D(2)O, and the orientational dynamics is studied with femtosecond polarization-resolved pump-probe spectroscopy of the O-D stretch vibration of HDO:H(2)O. Both the spectral and orientational dynamics are observed to show bimodal behavior: part of the water molecules shows spectral and orientational dynamics similar to bulk liquid water and part of the water molecules displays a much slower dynamics. For low solute concentrations, the latter fraction of slow water increases linearly as a function of solute molality, indicating that the slow water is contained in the solvation shells of TBA and TMAO. At higher concentrations, the fraction of slow water saturates. The saturation behavior is much stronger for TBA solutions than for TMAO solutions, indicating the aggregation of the TBA molecules. PMID- 21033813 TI - Copper-on-copper homoepitaxy studied by infrared spectroscopy of adsorbed CO. AB - Infrared spectroscopy of adsorbed CO was used to characterize the dependence of surface structure on deposition temperature during homoepitaxial growth on Cu(100). Intensity borrowing due to dipole coupling greatly enhances the absorption signal due to defect-bonded CO, making it possible to detect and quantify defect concentrations at the level of a few percent. For deposition temperatures between 300 and 400 K, the defect density increases slightly with decreasing deposition temperature but remains below 2%. There is a sharp increase in defect density, up to 5%-6%, as the deposition temperature is decreased from 300 to 250 K. At lower deposition temperatures, there is some sign of a leveling off in defect density, but the IR absorption spectrum becomes so broad that meaningful analysis becomes impractical, while visible degradation of the low energy electron diffraction pattern indicates worsening surface order. No indication of "re-entrant" ordering at low temperatures was observed for deposition temperatures down to 150 K. PMID- 21033814 TI - Capillary condensation in cylindrical pores: Monte Carlo study of the interplay of surface and finite size effects. AB - When a fluid that undergoes a vapor to liquid transition in the bulk is confined to a long cylindrical pore, the phase transition is shifted (mostly due to surface effects at the walls of the pore) and rounded (due to finite size effects). The nature of the phase coexistence at the transition depends on the length of the pore: for very long pores, the system is axially homogeneous at low temperatures. At the chemical potential where the transition takes place, fluctuations occur between vapor- and liquidlike states of the cylinder as a whole. At somewhat higher temperatures (but still far below bulk criticality), the system at phase coexistence is in an axially inhomogeneous multidomain state, where long cylindrical liquid- and vaporlike domains alternate. Using Monte Carlo simulations for the Ising/lattice gas model and the Asakura-Oosawa model of colloid-polymer mixtures, the transition between these two different scenarios is characterized. It is shown that the density distribution changes gradually from a double-peak structure to a triple-peak shape, and the correlation length in the axial direction (measuring the equilibrium domain length) becomes much smaller than the cylinder length. The (rounded) transition to the disordered phase of the fluid occurs when the axial correlation length has decreased to a value comparable to the cylinder diameter. It is also suggested that adsorption hysteresis vanishes when the transition from the simple domain state to the multidomain state of the cylindrical pore occurs. We predict that the difference between the pore critical temperature and the hysteresis critical temperature should increase logarithmically with the length of the pore. PMID- 21033815 TI - Modeling the noble metal/TiO2 (110) interface with hybrid DFT functionals: a periodic electrostatic embedded cluster model study. AB - The interaction of Au(n) and Pt(n) (n=2,3) clusters with the stoichiometric and partially reduced rutile TiO(2) (110) surfaces has been investigated using periodic slab and periodic electrostatic embedded cluster models. Compared to Au clusters, Pt clusters interact strongly with both stoichiometric and reduced TiO(2) (110) surfaces and are able to enhance the reducibility of the TiO(2) (110) surface, i.e., reduce the oxygen vacancy formation energy. The focus of this study is the effect of Hartree-Fock exchange on the description of the strength of chemical bonds at the interface of Au/Pt clusters and the TiO(2) (110) surface. Hartree-Fock exchange helps describing the changes in the electronic structures due to metal cluster adsorption as well as their effect on the reducibility of the TiO(2) surface. Finally, the performance of periodic embedded cluster models has been assessed by calculating the Pt adsorption and oxygen vacancy formation energies. Cluster models, together with hybrid PBE0 functional, are able to efficiently compute reasonable electronic structures of the reduced TiO(2) surface and predict charge localization at surface oxygen vacancies, in agreement with the experimental data, that significantly affect computed adsorption and reaction energies. PMID- 21033816 TI - Scanning tunneling microscopy/spectroscopy study of atomic and electronic structures of In2O on InAs and In0.53Ga0.47As(001)-(4*2) surfaces. AB - Interfacial bonding geometry and electronic structures of In(2)O on InAs and In(0.53)Ga(0.47)As(001)-(4*2) have been investigated by scanning tunneling microscopy/scanning tunneling spectroscopy (STM/STS). STM images show that the In(2)O forms an ordered monolayer on both InAs and InGaAs surfaces. In(2)O deposition on the InAs(001)-(4*2) surface does not displace any surface atoms during both room temperature deposition and postdeposition annealing. Oxygen atoms from In(2)O molecules bond with trough In/Ga atoms on the surface to form a new layer of O-In/Ga bonds, which restore many of the strained trough In/Ga atoms into more bulklike tetrahedral sp(3) bonding environments. STS reveals that for both p-type and n-type clean In(0.53)Ga(0.47)As(001)-(4*2) surfaces, the Fermi level resides near the valence band maximum (VBM); however, after In(2)O deposition and postdeposition annealings, the Fermi level position is close to the VBM for p-type samples and close to the conduction band minimum for n-type samples. This result indicates that In(2)O bonding eliminates surface states within the bandgap and forms an unpinned interface when bonding with In(0.53)Ga(0.47)As/InP(001)-(4*2). Density function theory is used to confirm the experimental finding. PMID- 21033817 TI - Relaxation of a semiflexible grafted polymer. AB - The relaxation of single grafted semiflexible chains freely rotating around the grafting point is investigated by means of two dimensional computer simulations and scaling arguments. Both free chains and chains surrounded by topological obstacles are considered. We compute the autocorrelation of the end-to-end vector for the whole chain and for terminal sections of various lengths. Our results are relevant for the relaxation of star polymers with stiff arms or branched semiflexible polymers moving in an array of obstacles. PMID- 21033818 TI - A topology preserving method for generating equilibrated polymer melts in computer simulations. AB - A new method for generating equilibrated configurations of polymer melts is presented. In this method, the molecular weight of an equilibrated melt of polymers is successively doubled by affinely scaling the simulation box and adding beads along the contour of the chains. At each stage of molecular weight doubling, compressive deformations are produced on all length scales, while the random walk nature of the polymers is preserved, thereby requiring relaxation times significantly smaller than the reptation time to fully equilibrate the melt. This method preserves the topological state of individual polymers in the melt and its effectiveness is demonstrated for linear polymers with molecular weight N up to 1024, and cyclic polymers with N up to 8192. For the range of N studied, the method requires simulation time that scales as N(2) and is thought to be applicable to a variety of polymer architectures. PMID- 21033819 TI - Pair interaction potentials of colloids by extrapolation of confocal microscopy measurements of collective suspension structure. AB - A method for measuring the pair interaction potential between colloidal particles by extrapolation measurement of collective structure to infinite dilution is presented and explored using simulation and experiment. The method is particularly well suited to systems in which the colloid is fluorescent and refractive index matched with the solvent. The method involves characterizing the potential of mean force between colloidal particles in suspension by measurement of the radial distribution function using 3D direct visualization. The potentials of mean force are extrapolated to infinite dilution to yield an estimate of the pair interaction potential, U(r). We use Monte Carlo simulation to test and establish our methodology as well as to explore the effects of polydispersity on the accuracy. We use poly-12-hydroxystearic acid-stabilized poly(methyl methacrylate) particles dispersed in the solvent dioctyl phthalate to test the method and assess its accuracy for three different repulsive systems for which the range has been manipulated by addition of electrolyte. PMID- 21033820 TI - Electric field assisted charge carrier photogeneration in poly(spirobifluorene-co benzothiadiazole). AB - The dynamics of charge carrier generation in poly(spirobifluorene-co benzothiadiazole) was investigated by electric field-induced fluorescence quenching and differential absorption measurements. Three different time domains of carrier generation have been identified: an ultrafast phase, a subnanosecond phase, and an entire lifetime phase. The charge generation efficiencies during the first and second phases were found to be almost independent of temperature, being about 25% and 10%, respectively, at an applied electric field of 1.3*10(6) V/cm, while the generation efficiency during the third phase increases from 2% at 80 K to 10% at room temperature. The results of transient spectroscopy measurements and quantum chemical calculations suggest an intramolecular charge transfer for about 1 ps from the alkoxy-substituted fluorene side group to the benzothiadiazole subunit of the main chain. The formation and evolution of the resulting charge transfer states determine the way of charge carrier generation. PMID- 21033821 TI - Conformational and rheological properties of semiflexible polymers in shear flow. AB - A theoretical description is provided for the nonequilibrium conformational and dynamical properties of a polymer in shear flow. Using a mean-field semiflexible chain model, which accounts for hydrodynamic interactions within the preaveraging approximation, analytical expressions are derived for the dependence of the deformation, orientation, and relaxation times on polymer persistence length and shear rate. Moreover, the rheological properties of a dilute polymer solution are discussed. The model yields shear thinning at large Weissenberg numbers. The analytical results are compared with fluorescence microscopy measurements of individual DNA molecules, which yield qualitative and partial quantitative agreement. PMID- 21033827 TI - Concept of a charged fusion product diagnostic for NSTX. AB - The concept of a new diagnostic for NSTX to determine the time dependent charged fusion product emission profile using an array of semiconductor detectors is presented. The expected time resolution of 1-2 ms should make it possible to study the effect of magnetohydrodynamics and other plasma activities (toroidal Alfven eigenmodes (TAE), neoclassical tearing modes (NTM), edge localized modes (ELM), etc.) on the radial transport of neutral beam ions. First simulation results of deuterium-deuterium (DD) fusion proton yields for different detector arrangements and methods for inverting the simulated data to obtain the emission profile are discussed. PMID- 21033823 TI - DNA capture into a nanopore: interplay of diffusion and electrohydrodynamics. AB - We present a detailed analysis of the process of voltage driven capture of DNA molecules by nanopores. We show that ionic current generates a nonuniform electric field that acts on both the DNA and on its counterions and that the response of DNA to the electric field is affected by its electroosmotic coupling to the mobile counterions. We calculate the voltage and molecular mass dependence of the radius of capture and of the capture rate in the diffusion limited regime. We argue that electroosmotic flow through the DNA coil is suppressed in the vicinity of the pore and present a tentative estimate of the capture rate in the barrier limited regime. PMID- 21033822 TI - Stochastic hybrid modeling of intracellular calcium dynamics. AB - Deterministic models of biochemical processes at the subcellular level might become inadequate when a cascade of chemical reactions is induced by a few molecules. Inherent randomness of such phenomena calls for the use of stochastic simulations. However, being computationally intensive, such simulations become infeasible for large and complex reaction networks. To improve their computational efficiency in handling these networks, we present a hybrid approach, in which slow reactions and fluxes are handled through exact stochastic simulation and their fast counterparts are treated partially deterministically through chemical Langevin equation. The classification of reactions as fast or slow is accompanied by the assumption that in the time-scale of fast reactions, slow reactions do not occur and hence do not affect the probability of the state. Our new approach also handles reactions with complex rate expressions such as Michaelis-Menten kinetics. Fluxes which cannot be modeled explicitly through reactions, such as flux of Ca(2+) from endoplasmic reticulum to the cytosol through inositol 1,4,5-trisphosphate receptor channels, are handled deterministically. The proposed hybrid algorithm is used to model the regulation of the dynamics of cytosolic calcium ions in mouse macrophage RAW 264.7 cells. At relatively large number of molecules, the response characteristics obtained with the stochastic and deterministic simulations coincide, which validates our approach in the limit of large numbers. At low doses, the response characteristics of some key chemical species, such as levels of cytosolic calcium, predicted with stochastic simulations, differ quantitatively from their deterministic counterparts. These observations are ubiquitous throughout dose response, sensitivity, and gene-knockdown response analyses. While the relative differences between the peak-heights of the cytosolic [Ca(2+)] time-courses obtained from stochastic (mean of 16 realizations) and deterministic simulations are merely 1%-4% for most perturbations, it is specially sensitive to levels of G(betagamma) (relative difference as large as 90% at very low G(betagamma)). PMID- 21033828 TI - A gated liquid-scintillator-based neutron detector for fast-ignitor experiments and down-scattered neutron measurements. AB - The detection of neutrons in fast-ignitor experiments or down-scattered neutrons in inertial fusion experiments is very challenging since it requires the neutron detection system to recover within 10-100 ns from a high background orders of magnitude stronger than the signal of interest. The background is either the hard x-ray emission from short-pulse laser target interactions for the fast-ignitor experiments or the primary neutron signal for the down-scattered neutrons. A liquid-scintillator detector has been developed using a gated photomultiplier that suppresses the background signal and eliminates the afterglow present in conventional plastic scintillators. PMID- 21033829 TI - Down-scattered neutron imaging detector for areal density measurement of inertial confinement fusion. AB - A custom developed (6)Li glass scintillator (APLF80+3Pr) for down-scattered neutron diagnostics in inertial confinement fusion experiments is presented. (6)Li provides an enhanced sensitivity for down-scattered neutrons in DD fusion and its experimentally observed 5-6 ns response time fulfills the requirement for down-scattered neutron detectors. A time-of-flight detector operating in the current mode using the APLF80+3Pr was designed and its feasibility observing down scattered neutrons was demonstrated. Furthermore, a prototype design for a down scattered neutron imaging detector was also demonstrated. This material promises viability as a future down-scattered neutron detector for the National Ignition Facility. PMID- 21033830 TI - Characteristics of four-channel Cherenkov-type detector for measurements of runaway electrons in the ISTTOK tokamak. AB - A diagnostics capable of characterizing the runaway and superthermal electrons has been developing on the ISTTOK tokamak. In previous paper, a use of single channel Cherenkov-type detector with titanium filter for runaway electron studies in ISTTOK was reported. To measure fast electron populations with different energies, a prototype of a four-channel detector with molybdenum filters was designed. Test-stand studies of filters with different thicknesses (1, 3, 7, 10, 20, 50, and 100 MUm) have shown that they should allow the detection of electrons with energies higher than 69, 75, 87, 95, 120, 181, and 260 keV, respectively. First results of measurements with the four-channel detector revealed the possibility to measure reliably different fast electrons populations simultaneously. PMID- 21033831 TI - Modeling the response of a fast ion loss detector using orbit tracing techniques in a neutral beam prompt-loss study on the DIII-D tokamak. AB - A numerical model describing the expected measurements of neutral beam prompt losses by a newly commissioned fast ion loss detector (FILD) in DIII-D is presented. This model incorporates the well understood neutral beam deposition profiles from all eight DIII-D beamlines to construct a prompt-loss source distribution. The full range of detectable ion orbit phase space available to the FILD is used to calculate ion trajectories that overlap with neutral beam injection footprints. Weight functions are applied to account for the level of overlap between these detectable orbits and the spatial and velocity (pitch) properties of ionized beam neutrals. An experimental comparison is performed by firing each neutral beam individually in the presence of a ramping plasma current. Fast ion losses determined from the model are in agreement with measured losses. PMID- 21033832 TI - A study on the neutron monitoring system of LHD based on Monte Carlo simulations. AB - Neutron monitoring is quite important because fusion neutrons are a direct evidence of fusion reactions. In calibration experiments of a neutron monitoring system, Monte Carlo calculations play an important role to correct various effects. To perform Monte Carlo calculations for a helical type fusion device, we make a program that can automatically generate an input file of a helical coil geometry for the MCNP code. The neutron spatial distributions and spectra for the helical devices are calculated in the geometries automatically generated by this program. We also discuss in calibration experiments. PMID- 21033833 TI - Scintillator-based diagnostic for fast ion loss measurements on DIII-D. AB - A new scintillator-based fast ion loss detector has been installed on DIII-D with the time response (>100 kHz) needed to study energetic ion losses induced by Alfven eigenmodes and other MHD instabilities. Based on the design used on ASDEX Upgrade, the diagnostic measures the pitch angle and gyroradius of ion losses based on the position of the ions striking the two-dimensional scintillator. For fast time response measurements, a beam splitter and fiberoptics couple a portion of the scintillator light to a photomultiplier. Reverse orbit following techniques trace the lost ions to their possible origin within the plasma. Initial DIII-D results showing prompt losses and energetic ion loss due to MHD instabilities are discussed. PMID- 21033834 TI - Development of in-vessel components of the microfission chamber for ITER. AB - Microfission chambers (MFCs) will measure the total neutron source strength in ITER. The MFCs will be installed behind blanket modules in the vacuum vessel (VV). Triaxial mineral insulated (MI) cables will carry signals from the MFCs. The joint connecting triaxial MI cables in the VV must be considered because the MFCs and the MI cables will be installed separately at different times. Vacuum tight triaxial connector of the MI cable has been designed and a prototype has been constructed. Performance tests indicate that the connector can be applied to the ITER environment. A small bending-radius test of the MI cable indicates no observed damage at a curvature radius of 100 mm. PMID- 21033835 TI - Development of neutron spectrometer toward deuterium plasma diagnostics in LHD. AB - Neutron spectrometer based on coincident counting of associated particles has been developed for deuterium plasma diagnostics on Large Helical Device (LHD) at the National Institute for Fusion Science. Efficient detection of 2.5 MeV neutron with high energy resolution would be achievable by coincident detection of a scattered neutron and a recoiled proton associated with an elastic scattering of incident neutron in a plastic scintillator as a radiator. The calculated neutron spectra from deuterium plasma heated by neutral beam injection indicate that the energy resolution of better than 7% is required for the spectrometer to evaluate energetic deuterium confinement. By using a prototype of the proposed spectrometer, the energy resolution of 6.3% and the detection efficiency of 3.3*10(-7) count/neutron were experimentally demonstrated for 2.5 MeV monoenergetic neutron, respectively. PMID- 21033836 TI - Fusion product diagnostics planned for Large Helical Device deuterium experiment. AB - Deuterium experiment on the Large Helical Device (LHD) is now being planned at the National Institute for Fusion Science. The fusion product diagnostics systems currently considered for installation on LHD are described in this paper. The systems will include a time-resolved neutron yield monitor based on neutron gas counters, a time-integrated neutron yield monitor based on activation techniques, a multicollimator scintillation detector array for diagnosing spatial distribution of neutron emission rate, 2.5 MeV neutron spectrometer, 14 MeV neutron counter, and prompt gamma-ray diagnostics. PMID- 21033837 TI - Progress toward the development and testing of source reconstruction methods for NIF neutron imaging. AB - Development of analysis techniques for neutron imaging at the National Ignition Facility is an important and difficult task for the detailed understanding of high-neutron yield inertial confinement fusion implosions. Once developed, these methods must provide accurate images of the hot and cold fuels so that information about the implosion, such as symmetry and areal density, can be extracted. One method under development involves the numerical inversion of the pinhole image using knowledge of neutron transport through the pinhole aperture from Monte Carlo simulations. In this article we present results of source reconstructions based on simulated images that test the methods effectiveness with regard to pinhole misalignment. PMID- 21033838 TI - Detection of lost alpha particle by concealed lost ion probe. AB - Full orbit-following calculation is performed for the final orbit of the lost alpha particles, showing some orbits escaping from the last closed flux surface could be detected by a concealed lost ion probe (CLIP) installed under the shadow of the original first wall surface. While both passing and trapped orbits hit the same wall panel, detecting a trapped orbit by the CLIP is easier than detecting passing orbits. Whether the final orbit is detected or not is determined by the position of the reflection point. The CLIP successfully detects the trapped orbits, which are reflected before they hit to a first wall. Then the pitch angles of the orbits at the CLIP are close to and smaller than 90 degrees . Optimization of the position of the CLIP in terms of broader detection window is investigated. PMID- 21033839 TI - Development and irradiation test of lost alpha detection system for ITER. AB - We developed a lost alpha detection system to use in burning plasma experiments. The scintillators of Ag:ZnS and polycrystalline Ce:YAG were designed for a high temperature environment, and the optical transmission line was designed to transmit from the scintillator to the port plug. The required optical components of lenses and mirrors were irradiated using the fission reactor with the initial result that there was no clear change after the irradiation with a neutron flux of 9.6*10(17) nm(-2) s(-1) for 48 h. We propose a diagnostic of alpha particle loss, so-called alpha particle induced gamma ray spectroscopy. The initial laboratory test has been carried out by the use of the Ce doped Lu(2)SiO(5) scintillator detector and an Am-Be source to detect the 4.44 MeV high energy gamma ray due to the (9)Be(alpha,ngamma)(12)C reaction. PMID- 21033840 TI - An imaging proton spectrometer for short-pulse laser plasma experiments. AB - The ultraintense short pulse laser pulses incident on solid targets can generate energetic protons. In addition to their potentially important applications such as in cancer treatments and proton fast ignition, these protons are essential to understand the complex physics of intense laser plasma interaction. To better characterize these laser-produced protons, we designed and constructed a novel spectrometer that will not only measure proton energy distribution with high resolution but also provide its angular characteristics. The information obtained from this spectrometer compliments those from commonly used diagnostics including radiochromic film packs, CR39 nuclear track detectors, and nonimaging magnetic spectrometers. The basic characterizations and sample data from this instrument are presented. PMID- 21033841 TI - A neutron camera system for MAST. AB - A prototype neutron camera has been developed and installed at MAST as part of a feasibility study for a multichord neutron camera system with the aim to measure the spatial and time resolved 2.45 MeV neutron emissivity profile. Liquid scintillators coupled to a fast digitizer are used for neutron/gamma ray digital pulse shape discrimination. The preliminary results obtained clearly show the capability of this diagnostic to measure neutron emissivity profiles with sufficient time resolution to study the effect of fast ion loss and redistribution due to magnetohydrodynamic activity. A minimum time resolution of 2 ms has been achieved with a modest 1.5 MW of neutral beam injection heating with a measured neutron count rate of a few 100 kHz. PMID- 21033842 TI - Extended fast-ion D-alpha diagnostic on DIII-D. AB - A fast-ion deuterium-alpha (FIDA) diagnostic, first commissioned on DIII-D in 2005, relies on Doppler-shifted light from charge-exchange between beam neutrals and energetic ions. The second generation (2G) system was installed on DIII-D in 2009. Its most obvious improvement is the spatial coverage with 11 active in-beam and three passive off-beam views; the latter allows for simultaneous monitoring of the background signal. Providing extended coverage in fast-ion velocity space, the new views possess a more tangential component with respect to the toroidal field compared to their first generation counterparts. Each viewing chord consists of a bundle of three 1.5 mm core fibers to maximize light gathering. For greater throughput, fast f/1.8 optical components are used throughout. The signal is transmitted via fiber optics to a patch panel, so the user is able to choose the detector. FIDA was originally installed with a spectrometer and charge coupled device (CCD) camera to monitor the full D(alpha) spectrum for two spatial views. 2G adds another spectrometer and CCD that monitor the blue-shifted wing for six spatial views at 1 kHz. In addition, a photomultiplier tube and fast digitizer provide wavelength-integrated signals at 1 MHz for eight spatial views. PMID- 21033843 TI - The response of a fast phosphor screen scintillator (ZnO:Ga) to low energy ions (0-60 keV). AB - ZnO:Ga is a promising, high time resolution candidate for use as a fast-ion-loss detector in TJ-II. We compare its ionoluminescence with that of the standard fast ion-loss detector material, SrGa(2)S(4):Eu (also known as TG-Green), when irradiated by H(+) ions with a range of energies E<=60 keV using a dedicated laboratory setup. It is found that ZnO:Ga is a reasonably good candidate for detecting low energy (E<60 keV) ions as it has excellent time resolution; however, its sensitivity is about 100 times lower than TG-Green, potentially limiting it to applications with high energy ion loss signals. PMID- 21033844 TI - Development and characterization of sub-100 ps photomultiplier tubes. AB - We describe the evaluation of a microchannel plate (MCP) photomultiplier tube (PMT), incorporating a 3 MUm pore MCP and constant voltage anode and cathode gaps. The use of the small pore size results in PMTs with response functions of the order of 85 ps full-width-half-maximum, while the constant electric field across the anode and cathode gaps produces a uniform response function over the entire operating range of the device. The PMT was characterized on a number of facilities and employed on gas Cherenkov detectors fielded on various deuterium tritium fuel (DT) implosions on the Omega Laser Facility at the University of Rochester. The Cherenkov detectors are part of diagnostic development to measure Gamma ray reaction history for DT implosions on the National Ignition Facility. PMID- 21033846 TI - Gamma bang time analysis at OMEGA. AB - Absolute bang time measurements with the gas Cherenkov detector (GCD) and gamma reaction history (GRH) diagnostic have been performed to high precision at the OMEGA laser facility at the University of Rochester with bang time values for the two diagnostics agreeing to within 5 ps on average. X-ray timing measurements of laser-target coupling were used to calibrate a facility-generated laser timing fiducial with rms spreads in the measured coupling times of 9 ps for both GCD and GRH. Increased fusion yields at the National Ignition Facility (NIF) will allow for improved measurement precision with the GRH easily exceeding NIF system design requirements. PMID- 21033845 TI - National Ignition Facility neutron time-of-flight measurements (invited). AB - The first 3 of 18 neutron time-of-flight (nTOF) channels have been installed at the National Ignition Facility (NIF). The role of these detectors includes yield, temperature, and bang time measurements. This article focuses on nTOF data analysis and quality of results obtained for the first set of experiments to use all 192 NIF beams. Targets produced up to 2*10(10) 2.45 MeV neutrons for initial testing of the nTOF detectors. Differences in neutron scattering at the OMEGA laser facility where the detectors were calibrated and at NIF result in different response functions at the two facilities. Monte Carlo modeling shows this difference. The nTOF performance on these early experiments indicates that the nTOF system with its full complement of detectors should perform well in future measurements of yield, temperature, and bang time. PMID- 21033847 TI - Development of novel fuel ion ratio diagnostic techniques. AB - To overcome the challenge of measuring the fuel ion ratio in the core (rho<0.3) of ITER, a coordinated effort aiming at developing diagnostic techniques has been initiated. The investigated techniques are novel uses or further development of existing methods such as charge exchange recombination spectrometry, neutron spectrometry, and collective Thomson scattering. An overview of the work on the three diagnostic techniques is presented. PMID- 21033848 TI - The National Ignition Facility neutron time-of-flight system and its initial performance (invited). AB - The National Ignition Facility (NIF) successfully completed its first inertial confinement fusion (ICF) campaign in 2009. A neutron time-of-flight (nTOF) system was part of the nuclear diagnostics used in this campaign. The nTOF technique has been used for decades on ICF facilities to infer the ion temperature of hot deuterium (D(2)) and deuterium-tritium (DT) plasmas based on the temporal Doppler broadening of the primary neutron peak. Once calibrated for absolute neutron sensitivity, the nTOF detectors can be used to measure the yield with high accuracy. The NIF nTOF system is designed to measure neutron yield and ion temperature over 11 orders of magnitude (from 10(8) to 10(19)), neutron bang time in DT implosions between 10(12) and 10(16), and to infer areal density for DT yields above 10(12). During the 2009 campaign, the three most sensitive neutron time-of-flight detectors were installed and used to measure the primary neutron yield and ion temperature from 25 high-convergence implosions using D(2) fuel. The OMEGA yield calibration of these detectors was successfully transferred to the NIF. PMID- 21033849 TI - Fast ion charge exchange spectroscopy adapted for tangential viewing geometry in LHD. AB - A tangential Fast Ion Charge eXchange Spectroscopy is newly applied on a Large Helical Device (LHD) for co/countercirculating fast ions, which are produced by high energy tangential negative-ion based neutral beam injection. With this new observation geometry, both the tangential-neutral beam (NB) and a low-energy radial-NB based on positive ions can be utilized as probe beams of the measurement. We have successfully observed Doppler-shifted H-alpha lights due to the charge exchange process between the probing NB and circulating hydrogen ions of around 100 keV in LHD plasmas. PMID- 21033850 TI - GEANT4 simulations of Cherenkov reaction history diagnostics. AB - This paper compares the results from a GEANT4 simulation of the gas Cherenkov detector 1 (GCD1) with previous simulations and experimental data from the Omega laser facility. The GCD1 collects gammas emitted during a deuterium-tritium capsule implosion and converts them, through several processes, to Cherenkov light. Photon signals are recorded using subnanosecond photomultiplier tubes, producing burn reaction histories. The GEANT4 GCD1 simulation is first benchmarked against ACCEPT, an integrated tiger series code, with good agreement. The simulation is subsequently compared with data from the Omega laser facility, where experiments have been performed to measure the effects of Hohlraum materials on reaction history signals, in preparation for experiments at the National Ignition Facility. PMID- 21033851 TI - Strategy for the absolute neutron emission measurement on ITER. AB - Accuracy of 10% is demanded to the absolute fusion measurement on ITER. To achieve this accuracy, a functional combination of several types of neutron measurement subsystem, cross calibration among them, and in situ calibration are needed. Neutron transport calculation shows the suitable calibration source is a DT/DD neutron generator of source strength higher than 10(10) n/s (neutron/second) for DT and 10(8) n/s for DD. It will take eight weeks at the minimum with this source to calibrate flux monitors, profile monitors, and the activation system. PMID- 21033852 TI - Using gamma-ray emission to measure areal density of inertial confinement fusion capsules. AB - Fusion neutrons streaming from a burning inertial confinement fusion capsule generate gamma rays via inelastic nuclear scattering in the ablator of the capsule. The intensity of gamma-ray emission is proportional to the product of the ablator areal density (rhoR) and the yield of fusion neutrons, so by detecting the gamma rays we can infer the ablator areal density, provided we also have a measurement of the capsule's total neutron yield. In plastic-shell capsules, for example, (12)C nuclei emit gamma rays at 4.44 MeV after excitation by 14.1 MeV neutrons from D+T fusion. These gamma rays can be measured by a new gamma-ray detector under development. Analysis of predicted signals is in progress, with results to date indicating that the method promises to be useful for diagnosing imploded capsules. PMID- 21033853 TI - Diagnosing inertial confinement fusion gamma ray physics (invited). AB - The gamma reaction history (GRH) diagnostic is a multichannel, time-resolved, energy-thresholded gamma-ray spectrometer that provides a high-bandwidth, direct measurement of fusion reaction history in inertial confinement fusion implosion experiments. 16.75 MeV deuterium+tritium (DT) fusion gamma-rays, with a branching ratio of the order of 10(-5)gamma/(14 MeV n), are detected to determine fundamental burn parameters, such as nuclear bang time and burn width, critical to achieving ignition at the National Ignition Facility. During the tritium/hydrogen/deuterium ignition tuning campaign, an additional gamma-ray line at 19.8 MeV, produced by hydrogen+tritium fusion with a branching ratio of unity, will increase the available gamma-ray signal and may allow measurement of reacting fuel composition or ion temperature. Ablator areal density measurements with the GRH are also made possible by detection of 4.43 MeV gamma-rays produced by inelastic scatter of DT fusion neutrons on (12)C nuclei in the ablating plastic capsule material. PMID- 21033854 TI - Fast neutron-gamma discrimination on neutron emission profile measurement on JT 60U. AB - A digital signal processing (DSP) system is applied to stilbene scintillation detectors of the multichannel neutron emission profile monitor in JT-60U. Automatic analysis of the neutron-gamma pulse shape discrimination is a key issue to diminish the processing time in the DSP system, and it has been applied using the two-dimensional (2D) map. Linear discriminant function is used to determine the dividing line between neutron events and gamma-ray events on a 2D map. In order to verify the validity of the dividing line determination, the pulse shape discrimination quality is evaluated. As a result, the gamma-ray contamination in most of the beam heating phase was negligible compared with the statistical error with 10 ms time resolution. PMID- 21033855 TI - Modeling the National Ignition Facility neutron imaging system. AB - Numerical modeling of the neutron imaging system for the National Ignition Facility (NIF), forward from calculated target neutron emission to a camera image, will guide both the reduction of data and the future development of the system. Located 28 m from target chamber center, the system can produce two images at different neutron energies by gating on neutron arrival time. The brighter image, using neutrons near 14 MeV, reflects the size and symmetry of the implosion "hot spot." A second image in scattered neutrons, 10-12 MeV, reflects the size and symmetry of colder, denser fuel, but with only ~1%-7% of the neutrons. A misalignment of the pinhole assembly up to +/-175 MUm is covered by a set of 37 subapertures with different pointings. The model includes the variability of the pinhole point spread function across the field of view. Omega experiments provided absolute calibration, scintillator spatial broadening, and the level of residual light in the down-scattered image from the primary neutrons. Application of the model to light decay measurements of EJ399, BC422, BCF99-55, Xylene, DPAC-30, and Liquid A suggests that DPAC-30 and Liquid A would be preferred over the BCF99-55 scintillator chosen for the first NIF system, if they could be fabricated into detectors with sufficient resolution. PMID- 21033856 TI - Development of CO2 laser dispersion interferometer with photoelastic modulator. AB - A dispersion interferometer is one of the promising methods of the electron density measurement on large and high density fusion devices. This paper describes development of a CO(2) laser dispersion interferometer with a photoelastic modulator for phase modulation. In order to make the dispersion interferometer free from variations of the detected intensity, a new phase extraction method is introduced: The phase shift is evaluated from a ratio of amplitudes of the fundamental and the second harmonics of the phase modulation frequency in the detected interference signal. The proof-of-principle experiments demonstrate the feasibility of this method. PMID- 21033857 TI - Design of far-infrared three-wave polarimeter-interferometer system for the J TEXT tokamak. AB - A multichannel three-wave far-infrared polarimeter-interferometer will be constructed on the J-TEXT tokamak (R=1.05 m, a=0.27 m, B(T)<=3 T, and I(P)<=350 kA) for current density profile and electron density profile measurements. The system will adopt the three-wave polarimeter configuration which was first introduced on RTP. Three 432.5 MUm HCOOH lasers pumped by three CO(2) lasers separately will be adopted, which could generate high output power, nearly 50 mW at each cavity. Two of them will be counter-rotating circularly polarized to probe the Faraday angle, while the third laser will be used as a local oscillator to get the phase shift caused by electron density. Excellent port access (600*76 mm(2)) and high laser power would promise a profile measurement across the whole plasma section with good signal quality. A high-speed digital phase comparator with a few (~2) MUs temporal resolution will be developed, so that fast changes of current or density profile could be measured. Six channels will be installed in the first stage. PMID- 21033858 TI - Far-forward collective scattering measurements of density fluctuations in the helically symmetric experiment stellarator. AB - The multichannel interferometer system on the helically symmetric experiment (HSX) stellarator is reconfigured to perform far-forward collective scattering measurements of electron density fluctuations. The collective scattering system has nine viewing chords with 1.5 cm spacing. Scattered power is measured using a homodyne detection scheme. Far-forward collective scattering provides a line integrated measurement of fluctuations within the divergence of the probe beam covering wavenumber range: k(?)<2 cm(-1). The perpendicular wavenumber consists of poloidal and radial contributions that vary with chord position. Both coherent modes and broadband fluctuation are measured. When HSX is operated without quasihelical symmetry at B(T)=1 T and n(e)~4*10(12) cm(-3), a coherent electrostatic fluctuation is observed. PMID- 21033859 TI - Collection optics design for KSTAR Thomson scattering system. AB - The collection optics designs are described for the Thomson scattering diagnostic of the Korea superconducting tokamak advanced research (KSTAR) device. The optical systems collecting the light emission induced through the interaction between the plasma electrons and a laser beam are key components for the Thomson scattering system. A duo-lens system was examined, and the final optical designs were derived for Thomson scattering diagnostic of KSTAR. PMID- 21033860 TI - Initial operation of a pulse-burst laser system for high-repetition-rate Thomson scattering. AB - A pulse-burst laser has been installed for Thomson scattering measurements on the Madison Symmetric Torus reversed-field pinch. The laser design is a master oscillator power-amplifier. The master oscillator is a commercial Nd:YVO(4) laser (1064 nm) which is capable of Q-switching at frequencies between 5 and 250 kHz. Four Nd:YAG (yttrium aluminum garnet) amplifier stages are in place to amplify the Nd:YVO(4) emission. Single pulses through the Nd:YAG amplifier stages gives energies up to 1.5 J and the gain for each stage has been measured. Repetitive pulsing at 10 kHz has also been performed for 2 ms bursts, giving average pulse energies of 0.53 J with DeltaE/E of 4.6%, where DeltaE is the standard deviation between pulses. The next step will be to add one of two Nd:glass (silicate) amplifier stages to produce final pulse energies of 1-2 J for bursts up to 250 kHz. PMID- 21033861 TI - Development of a nine spatial point, multipulse Thomson scattering diagnostic. AB - A Thomson scattering diagnostic has been developed for the C-2 field-reversed configuration device. Based on a multipulse ruby laser, the system measures the electron temperature at nine spatial points. These points are chosen from 22 selectable positions covering r~1-41 cm. Twin collection lenses couple the scattered photons to nine optical fiber pairs. Extra fiber lengths delay the signals from different spatial points relative to each other, allowing up to three points to be analyzed by a single polychromator. The polychromator, using compact photomultipliers as detectors, has six spectral channels covering the range of 685-725 nm and is able to estimate electron temperatures of ~10-200 eV. The photomultiplier output signals are recorded by digital storage oscilloscopes integrated with the main MDSplus database, with temperature and error estimates generated automatically at the conclusion of each plasma discharge. PMID- 21033862 TI - Preliminary results from the Alcator C-Mod polarimeter. AB - A poloidally viewing far infrared polarimeter diagnostic is being developed for the Alcator C-Mod tokamak, and will be used to determine the q-profile and to study density and magnetic field fluctuations. A three-chord version of what will eventually be up to a ten-chord system has been designed and fabricated and will be installed on C-Mod before the end of the current run period. Bench tests of a single chord mock-up of this system show acceptable noise levels for the planned measurements. We will discuss the analysis and experimental techniques used to diagnose and reduce noise sources. PMID- 21033863 TI - Upgrade of far-infrared laser-based Faraday rotation measurement on MST. AB - Recently, the far-infrared (FIR) laser (lambda(0)=432 MUm) Faraday rotation measurement system on MST has been upgraded. The dc flowing-gas discharge CO(2) pump laser is replaced by a rf-excited, sealed CO(2) laser at 9.27 MUm (GEM select 100, Coherent Inc., Santa Clara, CA), which is subdivided equally into three parts to simultaneously pump three FIR cavities. The total infrared pump power is approximately 80 W on the 9R(20) line required to pump the formic acid molecule. Each FIR cavity produces ~12 mW, sufficient for 11 simultaneous chord interferometry-polarimetry operations. Three key issues [(1) conservation of circularly polarized wave, (2) colinearity of two probe waves, and (3) stability of intermediate frequencies between lasers] affecting the Faraday rotation measurement have been resolved experimentally. PMID- 21033864 TI - Differential interferometry for measurement of density fluctuations and fluctuation-induced transport (invited). AB - Differential interferometry employs two parallel laser beams with a small spatial offset (less than beam width) and frequency difference (1-2 MHz) using common optics and a single mixer for a heterodyne detection. The differential approach allows measurement of the electron density gradient, its fluctuations, as well as the equilibrium density distribution. This novel interferometry technique is immune to fringe skip errors and is particularly useful in harsh plasma environments. Accurate calibration of the beam spatial offset, accomplished by use of a rotating dielectric wedge, is required to enable broad application of this approach. Differential interferometry has been successfully used on the Madison Symmetric Torus reversed-field pinch plasma to directly measure fluctuation-induced transport along with equilibrium density profile evolution during pellet injection. In addition, by combining differential and conventional interferometry, both linear and nonlinear terms of the electron density fluctuation energy equation can be determined, thereby allowing quantitative investigation of the origin of the density fluctuations. The concept, calibration, and application of differential interferometry are presented. PMID- 21033865 TI - Analysis of line integrated electron density using plasma position data on Korea Superconducting Tokamak Advanced Research. AB - A 280 GHz single-channel horizontal millimeter-wave interferometer system has been installed for plasma electron density measurements on the Korea Superconducting Tokamak Advanced Research (KSTAR) device. This system has a triangular beam path that does not pass through the plasma axis due to geometrical constraints in the superconducting tokamak. The term line density on KSTAR has a different meaning from the line density of other tokamaks. To estimate the peak density and the mean density from the measured line density, information on the position of the plasma is needed. The information has been calculated from tangentially viewed visible images using the toroidal symmetry of the plasma. Interface definition language routines have been developed for this purpose. The calculated plasma position data correspond well to calculation results from magnetic analysis. With the position data and an estimated plasma profile, the peak density and the mean density have been obtained from the line density. From these results, changes of plasma density themselves can be separated from effects of the plasma movements, so they can give valuable information on the plasma status. PMID- 21033866 TI - Laser system for high resolution Thomson scattering diagnostics on the COMPASS tokamak. AB - A new Thomson scattering diagnostic has been designed and is currently being installed on the COMPASS tokamak in IPP Prague in the Czech Republic. The requirements for this system are very stringent with approximately 3 mm spatial resolution at the plasma edge. A critical part of this diagnostic is the laser source. To achieve the specified parameters, a multilaser solution is utilized. Two 30 Hz 1.5 J Nd:YAG laser systems, used at the fundamental wavelength of 1064 nm, are located outside the tokamak area at a distance of 20 m from the tokamak. The design of the laser beam transport path is presented. The approach leading to a final choice of optimal focusing optics is given. As well as the beam path to the tokamak, a test path of the same optical length was built. Performance tests of the laser system carried out using the test path are described. PMID- 21033867 TI - Two-chord interferometry using 3.39 MUm He-Ne laser on a flux-coil-generated FRC. AB - A two-chord lambda(IR)~3.39 MUm He-Ne laser interferometer system was developed for a flux-coil-generated field-reversed configuration to estimate the electron density and the total temperature of the field-reversed configuration (FRC) plasma. This two-chord heterodyne interferometer system consists of a single ~2 mW infrared He-Ne laser, a visible (lambda(vis)~632.8 nm) He-Ne laser for the alignment, a 40 MHz acousto-optic modulator, photodetectors, and quadrature phase detectors. Initial measurement was performed and the measured average electron densities were 2-10*10(19) m(-3) at two different radial positions in the midplane. A time shift in density was observed as the FRC expands radially. The time evolution of the line-averaged density agrees with the density estimated from the in situ internal magnetic probes, based on a rigid-rotor profile model. PMID- 21033868 TI - Pulse-burst laser systems for fast Thomson scattering (invited). AB - Two standard commercial flashlamp-pumped Nd:YAG (YAG denotes yttrium aluminum garnet) lasers have been upgraded to "pulse-burst" capability. Each laser produces a burst of up to 15 2 J Q-switched pulses (1064 nm) at repetition rates of 1-12.5 kHz. Variable pulse-width drive (0.15-0.39 ms) of the flashlamps is accomplished by insulated gate bipolar transistor (IGBT) switching of electrolytic capacitor banks. Direct control of the laser Pockels cell drive enables optimal pulse energy extraction, and up to four 2 J laser pulses during one flashlamp pulse. These lasers are used in the Thomson scattering plasma diagnostic system on the MST reversed-field pinch to record the dynamic evolution of the electron temperature profile and temperature fluctuations. To further these investigations, a custom pulse-burst laser system with a maximum pulse repetition rate of 250 kHz is now being commissioned. PMID- 21033869 TI - Two dimensional density and its fluctuation measurements by using phase imaging method in GAMMA 10. AB - Two dimensional (2D) plasma image analysis is useful to study the improvement of plasma confinement in magnetically confined fusion plasmas. We have constructed a 2D interferometer system with phase imaging method for studying 2D plasma density distribution and its fluctuation measurement in the tandem mirror GAMMA 10. 2D profiles of electron density and its fluctuation have been successfully obtained by using this 2D phase imaging system. We show that 2D plasma density and fluctuation profiles clearly depends on the axial confining potential formation with application of plug electron cyclotron heating in GAMMA 10. PMID- 21033870 TI - Collective Thomson scattering measurements with high frequency resolution at TEXTOR. AB - We discuss the development and first results of a receiver system for the collective Thomson scattering (CTS) diagnostic at TEXTOR with frequency resolution in the megahertz range or better. The improved frequency resolution expands the diagnostic range and utility of CTS measurements in general and is a prerequisite for measurements of ion Bernstein wave signatures in CTS spectra. The first results from the new acquisition system are shown to be consistent with theory and with simultaneous measurements by the standard receiver system. PMID- 21033871 TI - Two-color CO2/HeNe laser interferometer for C-2 experiment. AB - A six-channel two-color interferometer has been developed for plasma electron density measurements in the C-2 field reversed configuration experiment. A CO(2) laser is utilized as the main probe beams, while copropagating visible HeNe laser beams are mainly sensitive to vibration. Density measurements in C-2 plasmas have shown that this is a reliable turn-key system. The maximum residual phase noise after vibration compensation is less than +/-5 degrees , corresponding to a line integral density of 3*10(18) m(-2). The time resolution for routine operation is 2 MUs. PMID- 21033872 TI - Two color multichannel heterodyne interferometer set up for high spatial resolution electron density profile measurements in TJ-II. AB - A high spatial resolution two color [CO(2), lambda=10.6 MUm/Nd:YAG (Nd:YAG denotes neodymium-doped yttrium aluminum garnet), and lambda=1.064 MUm] expanded beam multichannel heterodyne interferometer has been installed on the TJ-II stellarator. Careful design of the optical system has allowed complete control on the evolution of both Gaussian beams along the interferometer, as well as the evaluation and optimization of the spatial resolution to be expected in the measurements. Five CO(2) (measurement) channels and three Nd:YAG (vibration compensation) channels have been used to illuminate the plasma with a probe beam of 100 mm size. An optimum interpolation method has been applied to recover both interferometric phasefronts prior to mechanical vibration subtraction. The first results of the installed diagnostic are presented in this paper. PMID- 21033873 TI - A scalable multipass laser cavity based on injection by frequency conversion for noncollective Thomson scattering. AB - A scalable setup using injection by frequency conversion to establish a multipassing cavity for noncollective Thomson scattering on low density plasmas is presented. The cavity is shown to support >10 passes through the target volume with a 400% increase in energy on target versus a single-pass setup. Rayleigh scattering experiments were performed and demonstrate the viability of the cell to study low density plasmas of the order of 10(12)-10(13) cm(-3). A high repetition, low-energy, single-pass Thomson scattering setup was also performed on the University of California, Los Angeles Large Plasma Device and shows that the multipass cavity could have a significant advantage over the high-repetition approach due to the cavity setup's inherently higher signal per shot. PMID- 21033874 TI - Interaction between Faraday rotation and Cotton-Mouton effects in polarimetry modeling for NSTX. AB - The evolution of electromagnetic wave polarization is modeled for propagation in the major radial direction in the National Spherical Torus Experiment with retroreflection from the center stack of the vacuum vessel. This modeling illustrates that the Cotton-Mouton effect-elliptization due to the magnetic field perpendicular to the propagation direction-is shown to be strongly weighted to the high-field region of the plasma. An interaction between the Faraday rotation and Cotton-Mouton effects is also clearly identified. Elliptization occurs when the wave polarization direction is neither parallel nor perpendicular to the local transverse magnetic field. Since Faraday rotation modifies the polarization direction during propagation, it must also affect the resultant elliptization. The Cotton-Mouton effect also intrinsically results in rotation of the polarization direction, but this effect is less significant in the plasma conditions modeled. The interaction increases at longer wavelength and complicates interpretation of polarimetry measurements. PMID- 21033875 TI - A 130 point Nd:YAG Thomson scattering diagnostic on MAST. AB - A Thomson scattering diagnostic designed to measure both edge and core physics has been implemented on MAST. The system uses eight Nd:YAG lasers, each with a repetition rate of 30 Hz. The relative and absolute timing of the lasers may be set arbitrarily to produce fast bursts of measurements to suit the time evolution of the physics being studied. The scattered light is collected at F/6 by a 100 kg six element lens system with an aperture stop of 290 mm. The collected light is then transferred to 130 polychromators by 130 independent fiber bundles. The data acquisition and processing are based on a distributed computer system of dual core processors embedded in 26 chassis. Each chassis is standalone and performs data acquisition and processing for five polychromators. This system allows data to be available quickly after the MAST shot and has potential for real-time operations. PMID- 21033876 TI - MAST YAG Thomson scattering upgrade alignment system. AB - The recent upgrade to the MAST YAG Thomson scattering while enhancing the diagnostic capabilities increased the complexity of the system. There are eight YAG lasers now operational, doubling the number from the previous setup. This means alignment between each laser individually and reference points is essential to guarantee data quality and diagnostic reliability. To address this issue an alignment system was recently installed. It mimics the beams alignment in MAST by sampling 1% of the laser beam that is sent into a telescope which demagnifies by a factor of 8. The demagnified beam is viewed with a CCD camera. By scanning the camera the profile and position of the beams in the scattering zone and in a range of several meters inside MAST can be determined. Therefore alignment is checked along the beam path without having to sample it inside the vessel. The experimental apparatus and test procedures are described. PMID- 21033877 TI - Improvements of data quality of the LHD Thomson scattering diagnostics in high temperature plasma experiments. AB - In Large Helical Device (LHD) experiments, an electron temperature (T(e)) more than 15 keV has been observed by the yttrium-aluminum-garnet (YAG) laser Thomson scattering diagnostic. Since the LHD Thomson scattering system has been optimized for the temperature region, 50 eV<=T(e)<=10 keV, the data quality becomes worse in the higher T(e) region exceeding 10 keV. In order to accurately determine T(e) in the LHD high-T(e) experiments, we tried to increase the laser pulse energy by simultaneously firing three lasers. The technique enables us to decrease the uncertainties in the measured T(e). Another signal accumulation method was also tested. In addition, we estimated the influence of high-energy electrons on T(e) obtained by the LHD Thomson scattering system. PMID- 21033879 TI - 4omega Thomson scattering probe for high-density plasma characterization at Titan. AB - In preparation for the upcoming experiments on the Titan laser at the Jupiter Laser Facility, a new Thomson scattering system has been designed and implemented. This system allows electron temperature and density measurements in a high-density regime (n(e)>10(21) cm(-3)). A 263 nm probe has been demonstrated to produce a total energy of 15 J at 4omega(263 nm) in a 1 ns square pulse with a focal spot size of 100 MUm. This probe has been used for imaging Thomson scattering of the ion feature. The goal of this study is to investigate the heating of a preformed plasma by a short-pulse heater beam. PMID- 21033878 TI - Thomson-scattering measurements in the collective and noncollective regimes in laser produced plasmas (invited). AB - We present simultaneous Thomson-scattering measurements of light scattered from ion-acoustic and electron-plasma fluctuations in a N(2) gas jet plasma. By varying the plasma density from 1.5*10(18) to 4.0*10(19) cm(-3) and the temperature from 100 to 600 eV, we observe the transition from the collective regime to the noncollective regime in the high-frequency Thomson-scattering spectrum. These measurements allow an accurate local measurement of fundamental plasma parameters: electron temperature, density, and ion temperature. Furthermore, experiments performed in the high densities typically found in laser produced plasmas result in scattering from electrons moving near the phase velocity of the relativistic plasma waves. Therefore, it is shown that even at low temperatures relativistic corrections to the scattered power must be included. PMID- 21033880 TI - Thomson scattering diagnostic upgrade on DIII-D. AB - The DIII-D Thomson scattering system has been upgraded. A new data acquisition hardware was installed, adding the capacity for additional spatial channels and longer acquisition times for temperature and density measurements. Detector modules were replaced with faster transimpedance circuitry, increasing the signal to-noise ratio by a factor of 2. This allows for future expansion to the edge system. A second phase upgrade scheduled for 2010-2011 includes the installation of four 1 J/pulse Nd:YAG lasers at 50 Hz repetition rate. This paper presents the first completed phase of the upgrade and performance comparison between the original system and the upgraded system. The plan for the second phase is also presented. PMID- 21033881 TI - NSTX far infrared tangential interferometer/polarimeter electronics upgrade. AB - New electronics for the multichannel far infrared tangential interferometer/polarimeter system employed on the National Spherical Torus Experiment (NSTX) have greatly extended its capability to monitor high frequency density fluctuations. Such measurements are essential in understanding transport physics issues in NSTX as well as for the coming ITER device. The electronics, which were previously limited to ~250 kHz, have been upgraded with a video bandwidth that extends to 4 MHz when operating as an interferometry-only configuration, and to ~500 kHz when operating as a simultaneous interferometer/polarimeter system. Experimental details and test results of the new electronics are presented. PMID- 21033882 TI - Use of the Far Infrared Tangential Interferometer/Polarimeter diagnostic for the study of rf driven plasma waves on NSTX. AB - A rf detection system for waves in the 30 MHz range has been constructed for the Far Infrared Tangential Interferometer/Polarimeter on National Spherical Torus Experiment (NSTX). It is aimed at monitoring high frequency density fluctuations driven by 30 MHz high harmonic fast wave fields. The levels of density fluctuations at various radial chords and antenna phase angles can be estimated using the electric field calculated by TORIC code and linearized continuity equation for the electron density. In this paper, the experimental arrangement for the detection of rf signal and preliminary results of simulation will be discussed. PMID- 21033883 TI - Development of KSTAR Thomson scattering system. AB - To measure the electron temperature (T(e)) and electron density (n(e)) profiles in the Korean Superconducting Tokamak Advanced Research (KSTAR) device for the KSTAR third campaign (September 2010), we designed and installed a Thomson scattering system. The KSTAR Thomson scattering system is designed as a tangential Thomson scattering system and utilizes the N-, L-, and B-ports. The N port is designed for the collection optics with a cassette system, the L-port is the laser input port, and the B-port is the location of the beam dump. In this paper, we will describe the final design of the KSTAR Thomson scattering system. PMID- 21033884 TI - Comparative electron temperature measurements of Thomson scattering and electron cyclotron emission diagnostics in TCABR plasmas. AB - We present the first simultaneous measurements of the Thomson scattering and electron cyclotron emission radiometer diagnostics performed at TCABR tokamak with Alfven wave heating. The Thomson scattering diagnostic is an upgraded version of the one previously installed at the ISTTOK tokamak, while the electron cyclotron emission radiometer employs a heterodyne sweeping radiometer. For purely Ohmic discharges, the electron temperature measurements from both diagnostics are in good agreement. Additional Alfven wave heating does not affect the capability of the Thomson scattering diagnostic to measure the instantaneous electron temperature, whereas measurements from the electron cyclotron emission radiometer become underestimates of the actual temperature values. PMID- 21033885 TI - Imaging of the magnetic field structure in megagauss plasmas by combining pulsed polarimetry with an optical Kerr effect shutter technique. AB - Pulsed polarimetry in combination with a high speed photographic technique based on the optical Kerr effect is described. The backscatter in a pulsed polarimeter is directed through a scattering cell and photographed using an ~1 ps shutter, essentially freezing the intensity pattern. The image provides both the local electron density and magnetic field distributions along and transverse to the laser sightline. Submillimeter spatial resolution is possible for probing wavelengths in the visible due to the high densities and strong optical activity. Pulsed polarimetry is thereby extended to centimeter-sized plasmas with n(e)>10(19)-10(20) cm(-3) and B>20-100 T (MG) produced by multiterawatt, multimega-ampere electrical drivers, wire Z pinches, and liner imploded magnetized plasmas. PMID- 21033886 TI - Progress of development of Thomson scattering diagnostic system on COMPASS. AB - A new Thomson scattering diagnostic system has been designed and is being built now on the COMPASS tokamak at the Institute of Plasma Physics ASCR in Prague (IPP Prague) in the Czech Republic. This contribution focuses on design, development, and installation of the light collection and detection system. High spatial resolution of 3 mm will be achieved by a combination of design of collection optics and connected polychromators. Imaging characteristics of both core and edge plasma collection objectives are described and fiber backplane design is presented. Several calibration procedures are discussed. The operational deployment of the Thomson scattering diagnostic is planned by the end of 2010. PMID- 21033887 TI - Design of a new high repetition rate Nd:YAG Thomson scattering system for Heliotron J. AB - A new high repetition rate Nd:YAG Thomson scattering system has been designed for the Heliotron J helical device. The main purpose of installing the new Thomson scattering system is an investigation of an improved confinement physics such as the edge transport barrier (H-mode) or the internal transport barrier of the helical plasma. The system has 25 spatial points with ~10 mm resolution. Two high repetition Nd:YAG lasers (>550 mJ at 50 Hz) realize the measurement of the time evolution of the plasma profile with 10 ms time interval. Scattered light is collected with a large concave mirror (D=800 mm, f/2.25) with a solid angle of ~100 msr. The laser beam is injected from obliquely downward to upward, and obliquely backscattered light is detected (scattering angle is 20 degrees ). Model simulation of the polychromator shows the measurable electron temperature and density range are from 10 eV to 10 keV, >5*10(18) m(-3) within 3% error for the temperature measurement, respectively. PMID- 21033888 TI - Laser beam combiner for Thomson scattering core LIDAR. AB - The light detection and ranging Thomson scattering (TS) diagnostic is advantageous since it only requires a single view port into the tokamak. This technique requires a short pulse laser at high energy, usually showing a limited repetition rate. Having multiple lasers will increase the repetition rate. This paper presents a scanning mirror as a laser beam combiner. Measurements of the position accuracy and jitter show that the pointing stability of the laser beam is within +/-25 MUrad for over tens of seconds. A control feedback loop is implemented to demonstrate the long term stability. Such a system could be applied for ITER and JET. PMID- 21033889 TI - Collective Thomson scattering of a high power electron cyclotron resonance heating beam in LHD (invited). AB - Collective Thomson scattering (CTS) system has been constructed at LHD making use of the high power electron cyclotron resonance heating (ECRH) system in Large Helical Device (LHD). The necessary features for CTS, high power probing beams and receiving beams, both with well defined Gaussian profile and with the fine controllability, are endowed in the ECRH system. The 32 channel radiometer with sharp notch filter at the front end is attached to the ECRH system transmission line as a CTS receiver. The validation of the CTS signal is performed by scanning the scattering volume. A new method to separate the CTS signal from background electron cyclotron emission is developed and applied to derive the bulk and high energy ion components for several combinations of neutral beam heated plasmas. PMID- 21033890 TI - Development of two color laser diagnostics for the ITER poloidal polarimeter. AB - Two color laser diagnostics using terahertz laser sources are under development for a high performance operation of the Large Helical Device and for future fusion devices such as ITER. So far, we have achieved high power laser oscillation lines simultaneously oscillating at 57.2 and 47.7 MUm by using a twin optically pumped CH(3)OD laser, and confirmed the original function, compensation of mechanical vibration, of the two color laser interferometer. In this article, application of the two color laser diagnostics to the ITER poloidal polarimeter and recent hardware developments will be described. PMID- 21033891 TI - Design of collection optics and polychromators for a JT-60SA Thomson scattering system. AB - This paper presents designs of collection optics for a JT-60SA Thomson scattering system. By using tangential (to the toroidal direction) YAG laser injection, three collection optics without strong chromatic aberration generated by the wide viewing angle and small design volume were found to measure almost all the radial space. For edge plasma measurements, the authors optimized the channel number and wavelength ranges of band-pass filters in a polychromator to reduce the relative error in T(e) by considering all spatial channels and a double-pass laser system with different geometric parameters. PMID- 21033892 TI - Fringe-jump corrected far infrared tangential interferometer/polarimeter for a real-time density feedback control system of NSTX plasmas. AB - The far infrared tangential interferometer/polarimeter (FIReTIP) of the National Spherical Torus Experiment (NSTX) has been set up to provide reliable electron density signals for a real-time density feedback control system. This work consists of two main parts: suppression of the fringe jumps that have been prohibiting the plasma density from use in the direct feedback to actuators and the conceptual design of a density feedback control system including the FIReTIP, control hardware, and software that takes advantage of the NSTX plasma control system (PCS). By investigating numerous shot data after July 2009 when the new electronics were installed, fringe jumps in the FIReTIP are well characterized, and consequently the suppressing algorithms are working properly as shown in comparisons with the Thomson scattering diagnostic. This approach is also applicable to signals taken at a 5 kHz sampling rate, which is a fundamental constraint imposed by the digitizers providing inputs to the PCS. The fringe jump correction algorithm, as well as safety and feedback modules, will be included as submodules either in the gas injection system category or a new category of density in the PCS. PMID- 21033893 TI - Conceptual design of the collection optics for the edge Thomson scattering system in ITER. AB - Neutron and gamma-ray irradiation complicates the design of the edge Thomson scattering (TS) system in ITER. The TS light is relayed through the relaying optics with labyrinth and fiber coupling optics. Electron density of 2*10(19) m( 3) is sufficient to measure T(e) and n(e) within a 10% and 5% margin of error, respectively, with a spatial resolution of 5 mm. This system can cover from 0.85 to 1 of the normalized minor radius. The time resolution is 10 ms, which is determined by the repetition rate of the laser device. A super-Gaussian is the ideal laser profile for the laser injection optics to avoid a breakdown of the filling gas used in density calibration through Raman scattering. PMID- 21033894 TI - Simultaneous two-dimensional laser-induced-fluorescence measurements of argon ions. AB - Recent laser upgrades on the Hot Helicon Experiment at West Virginia University have enabled multiplexed simultaneous measurements of the ion velocity distribution function at a single location, expanding our capabilities in laser induced fluorescence diagnostics. The laser output is split into two beams, each modulated with an optical chopper and injected perpendicular and parallel to the magnetic field. Light from the crossing point of the beams is transported to a narrow-band photomultiplier tube filtered at the fluorescence wavelength and monitored by two lock-in amplifiers, each referenced to one of the two chopper frequencies. PMID- 21033895 TI - Two-point motional Stark effect diagnostic for Madison Symmetric Torus. AB - A high-precision spectral motional Stark effect (MSE) diagnostic provides internal magnetic field measurements for Madison Symmetric Torus (MST) plasmas. Currently, MST uses two spatial views--on the magnetic axis and on the midminor (off-axis) radius, the latter added recently. A new analysis scheme has been developed to infer both the pitch angle and the magnitude of the magnetic field from MSE spectra. Systematic errors are reduced by using atomic data from atomic data and analysis structure in the fit. Reconstructed current density and safety factor profiles are more strongly and globally constrained with the addition of the off-axis radius measurement than with the on-axis one only. PMID- 21033896 TI - Integrated analysis and consistency measurement of bremsstrahlung and charge exchange spectroscopy data for the determination of the ion effective charge. AB - In the context of Bayesian probability theory, we discuss a model for estimating the plasma ion effective charge Z(eff), integrating data from both bremsstrahlung spectroscopy and individual impurity concentrations obtained via charge exchange spectroscopy (CXS). The validity of the model, taking into account statistical as well as systematic uncertainties, is shown via the deviance information criterion. The consistency of the continuum and CXS data regarding Z(eff) is improved, as measured by the symmetrized Kullback-Leibler divergence and the geodesic distance between the respective Z(eff) marginal posterior densities. PMID- 21033897 TI - Measurements of neutral helium density in helicon plasmas. AB - Laser-induced-fluorescence (LIF) is used to measure the density of helium atoms in a helicon plasma source. For a pump wavelength of 587.725 nm (vacuum) and laser injection along the magnetic field, the LIF signal exhibits a signal decrease at the Doppler shifted central wavelength. The drop in signal results from the finite optical depth of the plasma and the magnitude of the decrease is proportional to the density of excited state neutral atoms. Using Langmuir probe measurements of plasma density and electron temperature and a collisional radiative model, the absolute ground state neutral density is calculated from the optical depth measurements. Optimal plasma performance, i.e., the largest neutral depletion on the axis of the system, is observed for antenna frequencies of 13.0 and 13.5 MHz and magnetic field strengths of 550-600 G. PMID- 21033898 TI - Impurity temperature correction factors for the transmission grating spectrometer in the TJ-II stellarator. AB - Impurity ion temperature and velocity profiles are obtained across plasmas in the TJ-II stellarator by performing charge-exchange recombination spectroscopy with a diagnostic neutral beam injector. For this, a tridirectional (toroidal plus two poloidal opposing views) multichannel spectroscopic diagnostic, incorporating 12 way fiber arrays, a compact f/1.8 spectrograph, and a back-illuminated CCD, permits Doppler line shifts and widths (of the C VI line at 529.05 nm) to be determined with 1-2 cm spatial resolution. For good photon counting statistics under Li-coated wall conditions, 600 MUm diameter fibers collect and transmit light to curved 100 MUm wide input slits. When calibrated with a neon pencil lamp this entrance slit width results in a non-Gaussian instrumental function that, if not handled correctly, can result in systematically underestimated impurity temperatures. Here we develop and present correction factors for this effect for a range of conditions. PMID- 21033899 TI - Z(eff) measurement using extreme ultraviolet bremsstrahlung emission in LHD. AB - Radial profile measurement of Z(eff) using visible bremsstrahlung (5300 A) in the Large Helical Device (LHD) has often encountered difficulties because the intensity profile was largely deformed by the nonuniform visible bremsstrahlung emissions from the edge ergodic layer surrounding the core plasma. A space resolved flat-field extreme ultraviolet (EUV) spectrometer has been newly adopted to measure the Z(eff) profile using the EUV bremsstrahlung continuum in the wavelength range of 70-75 A. The EUV bremsstrahlung intensity profiles have been measured and checked for all the magnetic configurations with totally different magnetic field structures in the ergodic layer of LHD. It is found that the nonuniform bremsstrahlung emission from the thick ergodic layer can be entirely eliminated by use of the EUV emission with relatively high photon energy of 170 eV. As a result, the Z(eff) profile can be successfully measured for most of discharges regardless of magnetic field structures of the ergodic layer. The Z(eff) profiles measured in the EUV range are compared with those measured in the visible range at a magnetic configuration with the thinnest ergodic layer thickness. The result verifies that the use of the EUV bremsstrahlung continuum is an alternative way for the Z(eff) measurement in toroidal plasmas with nonuniform bremsstrahlung emissions at the edge. Typical results from the EUV bremsstrahlung measurement are presented showing a fairly flat Z(eff) profile with error bars of +/-14%. PMID- 21033900 TI - Measuring the density of a molecular cluster injector via visible emission from an electron beam. AB - A method to measure the density distribution of a dense hydrogen gas jet is presented. A Mach 5.5 nozzle is cooled to 80 K to form a flow capable of molecular cluster formation. A 250 V, 10 mA electron beam collides with the jet and produces H(alpha) emission that is viewed by a fast camera. The high density of the jet, several 10(16) cm(-3), results in substantial electron depletion, which attenuates the H(alpha) emission. The attenuated emission measurement, combined with a simplified electron-molecule collision model, allows us to determine the molecular density profile via a simple iterative calculation. PMID- 21033901 TI - Toward a full exploitation of the helium beam edge diagnostic. AB - In this article, extension of the He beam diagnostic, which is routinely applied in fusion devices for the characterization of the edge electronic parameters-ne and Te-and their profile, to the measurement of ion temperature and plasma rotation is proposed. The theoretical background for these new applications is reviewed and examples of their use in TJ-II are provided. Also, the shortcomings and their possible solutions are addressed. Finally, the field of application of the technique to other beam-based diagnostics is discussed. PMID- 21033902 TI - An integrated charge exchange recombination spectroscopy/beam emission spectroscopy diagnostic for Alcator C-Mod tokamak. AB - A novel integrated charge exchange recombination spectroscopy (CXRS)/beam emission spectroscopy (BES) system is proposed for C-Mod, in which both measurements are taken from a shared viewing geometry. The supplementary BES system serves to quantify local beam densities and supplants the common calculation of beam attenuation. The new system employs two optical viewing arrays, 20 poloidal and 22 toroidal channels. A dichroic filter splits the light between two spectrometers operating at different wavelengths for impurity ion and beam neutrals emission. In this arrangement, the impurity density is inferred from the electron density, measured BES and CXRS spectral radiances, and atomic emission rates. PMID- 21033903 TI - Design of a cavity ring-down spectroscopy diagnostic for negative ion rf source SPIDER. AB - The rf source test facility SPIDER will test and optimize the source of the 1 MV neutral beam injection systems for ITER. Cavity ring-down spectroscopy (CRDS) will measure the absolute line-of-sight integrated density of negative (H(-) and D(-)) ions, produced in the extraction region of the source. CRDS takes advantage of the photodetachment process: negative ions are converted to neutral hydrogen atoms by electron stripping through absorption of a photon from a laser. The design of this diagnostic is presented with the corresponding simulation of the expected performance. A prototype operated without plasma has provided CRDS reference signals, design validation, and results concerning the signal-to-noise ratio. PMID- 21033905 TI - Development of laser induced fluorescence diagnostic for measuring the parameters of plasma containing rare gas species. AB - Laser induced fluorescence (LIF) technique development activity for measurement of plasma parameters in ITER divertor plasma is described. Helium density is the task of priority, but Doppler measurement of ion (atom) temperatures is also the aim of the program. The concept of ITER scenarios includes injection of "extrinsic" impurities (Ne, Ar, and Kr). It is possible to use the species as tracing elements for measurement of T(i), T(a). The program included modeling experiments on PNX-U (a multicusp trap with microwave argon plasma). Helium was added by puffing into discharge. Temperatures T(i)(Ar(1+)) and T(a)(He(0)) have been measured by scanning laser line across absorption line of species. Summarizing of fluorescence signals provided input data for estimation of Ar(1+) and He(0) densities via interpretative collisional-radiative models. Besides, the collisional-radiative model has been used for estimation of electron density using the ratio of fluorescence signals at 388.9 and 706.5 nm helium lines. PMID- 21033904 TI - Implementation of multifilter based twin-prototypes for core electron temperature measurements in the TJ-II stellarator. AB - The design and preliminary results from a prototype of a multifilter based electron temperature diagnostic for the TJ-II stellarator are presented. The diagnostic consists of four photodiodes with filters of different thicknesses to determine the electron temperature in a wide variety of plasma compositions, thanks to the set of six different signal-pairs ratios available. The impurity transport code IONEQ, the TJ-II soft x-ray tomography, and the VUV survey diagnostics give the necessary information to assess the proposed diagnostic reliability. In parallel, a vacuum-compatible multichannel electronic board has been designed for a future linear array to determine electron temperature profiles in high-density plasmas. PMID- 21033906 TI - Calculation of spatial response of 2D beam emission spectroscopy diagnostic on MAST. AB - The beam emission spectroscopy (BES) turbulence diagnostic on MAST is to be upgraded in June 2010 from a one-dimensional trial system to a two-dimensional imaging system (8 radial*4 poloidal channels) based on a newly developed avalanche photodiode array camera. The spatial resolution of the new system is calculated in terms of the point spread function to account for the effects of field-line curvature, observation geometry, the finite lifetime of the excited state of the beam atoms, and beam attenuation and divergence. It is found that the radial spatial resolution is ~2-3 cm and the poloidal spatial resolution ~1-5 cm depending on the radial viewing location. The absolute number of detected photons is also calculated, hence the photon noise level can be determined. PMID- 21033907 TI - Ultrafast spectroscopy diagnostic to measure localized ion temperature and toroidal velocity fluctuations. AB - A dual-channel high-efficiency, high-throughput custom spectroscopic system has been designed and implemented at DIII-D to measure localized ion thermal fluctuations associated with drift wave turbulence. A large-area prism-coupled transmission grating and high-throughput collection optics are employed to observe C VI emission centered near lambda=529 nm. The diagnostic achieves 0.25 nm resolution over a 2.0 nm spectral band via eight discrete spectral channels. A turbulence-relevant time resolution of 1 MUs is achieved using cooled high-speed avalanche photodiodes and ultralow-noise preamplifiers. The system sensitivity is designed to provide measurements of normalized ion temperature fluctuations on the order of deltaT(i)/T(i)<=1%. PMID- 21033908 TI - Optical measurements for turbulence characterization in RFX-mod edge. AB - The edge of the reversed field pinch experiment RFX-mod (R=2 m, a=0.46 m) is characterized by a complex magnetic topology and strong pressure gradients. A set of fast spectroscopic diagnostics has been designed to characterize both main plasma edge parameters and turbulence, including coherent structures (blobs) and radial profiles of the thermodynamic variables. Measurements of the edge radial profiles of electron density (n(e)), temperature (T(e)), and pressure (P(e)) are obtained by a thermal helium beam diagnostic, which locally measures the ratios of the spectral lines emitted by a neutral He cloud puffed into hydrogen plasma discharges. A gas puff imaging system allows the high frequency (1 MHz bandwidth) measurement of the fluctuations of He I emissivity in the same positions. The system measures both the intermittent behavior of the edge turbulence and n(e), T(e), and P(e) profiles of the corresponding coherent structures, with a resolution down to 6 MUs. The optical diagnostics are complemented by a set of triaxial magnetic coils to simultaneously characterize the edge magnetic field. PMID- 21033909 TI - Toroidal charge exchange recombination spectroscopy measurements on MST. AB - Charge exchange recombination spectroscopy measurements of the poloidal component of the C(+6) temperature and flow in the Madison Symmetric Torus have been vital in advancing the understanding of the ion dynamics in the reversed field pinch. Recent work has expanded the diagnostic capability to include toroidal measurements. A new toroidal view overcomes a small signal-to-background ratio (5%-15%) to make the first localized measurements of the parallel component of the impurity ion temperature in the core of the reversed field pinch. The measurement is made possible through maximal light collection in the optical design and extensive atomic modeling in the fitting routine. An absolute calibration of the system allowed the effect of Poisson noise in the signal on line fitting to be quantified. The measurement is made by stimulating emission with a recently upgraded 50 keV hydrogen diagnostic neutral beam. Radial localization is ~4 cm(2), and good temporal resolution (100 MUs) is achieved by making simultaneous emission and background measurements with a high-throughput double-grating spectrometer. PMID- 21033910 TI - Overview of the beam emission spectroscopy diagnostic system on the National Spherical Torus Experiment. AB - A beam emission spectroscopy (BES) system has been installed on the National Spherical Torus Experiment (NSTX) to study ion gyroscale fluctuations. The BES system measures D(alpha) emission from a deuterium neutral heating beam. The system includes two optical views centered at r/a~0.45 and 0.85 and aligned to magnetic field pitch angles at the neutral beam. f/1.5 collection optics produce 2-3 cm spot sizes at the neutral beam. The initial channel layout includes radial arrays, poloidal arrays, and two-dimensional grids. Radial arrays provide coverage from r/a~0.1 to beyond the last-closed flux surface. Photodetectors and digital filters provide high-sensitivity, low-noise measurements at frequencies of up to 1 MHz. The BES system will be a valuable tool for investigating ion gyroscale turbulence and Alfven/energetic particle modes on NSTX. PMID- 21033911 TI - Low-noise, high-speed detector development for optical turbulence fluctuation measurements for NSTX. AB - A new beam emission spectroscopy (BES) diagnostic is under development. Photon noise limited measurements of neutral beam emissions are achieved using photoconductive photodiodes with a novel frequency-compensated broadband preamplifier. The new BES system includes a next-generation preamplifier and upgraded optical coupling system. Notable features of the design are surface mount components, minimized stray capacitance, a wide angular acceptance photodiode, a differential output line driver, reduced input capacitance, doubling of the frequency range, net reduced electronic noise, and elimination of the need for a cryogenic cooling system. The irreducible photon noise dominates the noise up to 800 kHz for a typical input power of 60 nW. This new assembly is being integrated into an upgraded multichannel optical detector assembly for a new BES system on the NSTX experiment. PMID- 21033912 TI - Poloidal beam emission spectroscopy system for the measurement of density fluctuations in Large Helical Device. AB - A system of beam emission spectroscopy (BES) for density fluctuation measurements having the sightlines passing through the plasma in the poloidal direction was developed in the Large Helical Device (LHD). Even though the angle between the beam and the sightline is slightly larger than a right angle, Doppler-shifted beam emission can be distinguished from background emission because of the high energy (120-170 keV) of the neutral beam for heating with negative ion sources. Spatial resolution is about 0.1-0.2 in the normalized radius. Compared with the prototype BES system with toroidal sightlines, the BES system with poloidal sightlines showed improved spatial resolution. PMID- 21033913 TI - Grating spectrometer system for beam emission spectroscopy diagnostics using high energy negative-ion-based neutral beam injection on LHD. AB - A beam emission spectroscopy (BES) system was developed for density gradient and fluctuation diagnostics in the Large Helical Device (LHD). In order to cover the large Doppler shift of the Halpha beam emission because of the high-energy negative-ion-based neutral beam atom (acceleration voltage V(acc)=90-170 kV) and the large motional Stark splitting due to the large v*B field (magnetic field B=3.0 T), a grating spectrometer was used instead of a conventional interference filter system. The reciprocal linear dispersion is about 2 nm/mm, which is sufficient to cover the motional Stark effect spectra using an optical fiber with a diameter of 1 mm. PMID- 21033914 TI - Charge exchange recombination detection of low-Z and medium-Z impurities in the extreme UV using a digital lock-in technique. AB - More sensitive detection of charge exchange recombination lines from low-Z elements, and first-time detection from the medium-Z elements nickel and copper, has been achieved in DIII-D plasmas with a digital lock-in technique. That portion of the extreme UV spectrum varying synchronously in time with the square wave modulation of a high energy, neutral heating beam is extracted by forming a scalar product of a correlation function with the data record of each pixel in the linear array detector. The usual, dense array of collisionally excited, metallic lines from the tokamak plasma is strongly suppressed, leaving only a sparse spectrum of lines dominated by charge exchange recombination transitions from fully stripped, low-Z elements. In plasmas with high metal content, charge exchange recombination lines from the Li-like ions of nickel and copper have been positively identified. PMID- 21033915 TI - Available information in 2D motional Stark effect imaging. AB - Recent advances in imaging techniques have allowed the extension of the standard polarimetric 1D motional Stark effect (MSE) diagnostic to 2D imaging of the internal magnetic field of fusion devices [J. Howard, Plasma Phys. Controlled Fusion 50, 125003 (2008)]. This development is met with the challenge of identifying and extracting the new information, which can then be used to increase the accuracy of plasma equilibrium and current density profile determinations. This paper develops a 2D analysis of the projected MSE polarization orientation and Doppler phase shift. It is found that, for a standard viewing position, the 2D MSE imaging system captures sufficient information to allow imaging of the internal vertical magnetic field component B(Z)(r,z) in a tokamak. PMID- 21033916 TI - Spectroscopic diagnostics for liquid lithium divertor studies on National Spherical Torus Experiment. AB - The use of lithium-coated plasma facing components for plasma density control is studied in the National Spherical Torus Experiment (NSTX). A recently installed liquid lithium divertor (LLD) module has a porous molybdenum surface, separated by a stainless steel liner from a heated copper substrate. Lithium is deposited on the LLD from two evaporators. Two new spectroscopic diagnostics are installed to study the plasma surface interactions on the LLD: (1) A 20-element absolute extreme ultraviolet (AXUV) diode array with a 6 nm bandpass filter centered at 121.6 nm (the Lyman-alpha transition) for spatially resolved divertor recycling rate measurements in the highly reflective LLD environment, and (2) an ultraviolet-visible-near infrared R=0.67 m imaging Czerny-Turner spectrometer for spatially resolved divertor D I, Li I-II, C I-IV, Mo I, D(2), LiD, CD emission and ion temperature on and around the LLD module. The use of photometrically calibrated measurements together with atomic physics factors enables studies of recycling and impurity particle fluxes as functions of LLD temperature, ion flux, and divertor geometry. PMID- 21033917 TI - Measurement of poloidal velocity on the National Spherical Torus Experiment (invited). AB - A diagnostic suite has been developed to measure the impurity poloidal flow using charge exchange recombination spectroscopy on the National Spherical Torus Experiment. Toroidal and poloidal viewing systems measure all the quantities required to determine the radial electric field. Two sets of up/down symmetric poloidal views are used to measure both the active emission in the plane of the neutral heating beams and the background emission in a radial plane away from the neutral beams. Differential velocity measurements isolate the line-integrated poloidal velocity from apparent flows due to the energy-dependent charge exchange cross section. Six f/1.8 spectrometers measure 276 spectra to obtain 75 active and 63 background channels every 10 ms. The local measurements from a similar midplane toroidal viewing system are mapped into two dimensions to allow the inversion of poloidal line-integrated measurements to obtain local poloidal velocity profiles. The radial resolution after inversion is 0.6-1.8 cm from the plasma edge to the center. PMID- 21033918 TI - Active spectroscopic measurements using the ITER diagnostic system. AB - Active (beam-based) spectroscopic measurements are intended to provide a number of crucial parameters for the ITER device being built in Cadarache, France. These measurements include the determination of impurity ion temperatures, absolute densities, and velocity profiles, as well as the determination of the plasma current density profile. Because ITER will be the first experiment to study long timescale (~1 h) fusion burn plasmas, of particular interest is the ability to study the profile of the thermalized helium ash resulting from the slowing down and confinement of the fusion alphas. These measurements will utilize both the 1 MeV heating neutral beams and a dedicated 100 keV hydrogen diagnostic neutral beam. A number of separate instruments are being designed and built by several of the ITER partners to meet the different spectroscopic measurement needs and to provide the maximum physics information. In this paper, we describe the planned measurements, the intended diagnostic ensemble, and we will discuss specific physics and engineering challenges for these measurements in ITER. PMID- 21033919 TI - Application of beam emission spectroscopy to NBI plasmas of Heliotron J. AB - This paper describes the application of the beam emission spectroscopy (BES) to Heliotron J, having the nonsymmetrical helical-magnetic-axis configuration. The spectral and spatial profile of the beam emission has been estimated by the numerical calculation taking the collisional excitation processes between plasmas (electrons/ions) and beam atoms. Two sets of the sightlines with good spatial resolution are presented. One is the optimized viewing chords which have 20 sightlines and observe the whole plasma region with the spatial resolution Deltarho less than +/-0.055 using the newly designed viewing port. The other is 15 sightlines from the present viewing port of Heliotron J for the preliminary measurement to discuss the feasibility of the density fluctuation measurement by BES. The beam emission has been measured by a monochromator with a CCD camera. A good consistency has been obtained between the spectral profiles of the beam emission measured by the monochromator and the beam emission spectrum deduced by the model calculation. An avalanche photodiode with an interference filter system was also used to evaluate the signal-to-noise (S/N) ratio of the beam emission in the present experimental setup. The modification of the optical system is being planned to improve the S/N ratio, which will enable us to estimate the density fluctuation in Heliotron J. PMID- 21033920 TI - Fast-ion Dalpha measurements of the fast-ion distribution (invited). AB - The fast-ion Dalpha (FIDA) diagnostic is an application of charge-exchange recombination spectroscopy. Fast ions that neutralize in an injected neutral beam emit Balmer-alpha light with a large Doppler shift. The spectral shift is exploited to distinguish the FIDA emission from other bright sources of Dalpha light. Background subtraction is the main technical challenge. A spectroscopic diagnostic typically achieves temporal, energy, and transverse spatial resolution of ~1 ms, ~10 keV, and ~2 cm, respectively. Installations that use narrow-band filters achieve high spatial and temporal resolution at the expense of spectral information. For high temporal resolution, the bandpass-filtered light goes directly to a photomultiplier, allowing detection of ~50 kHz oscillations in FIDA signal. For two-dimensional spatial profiles, the bandpass-filtered light goes to a charge-coupled device camera; detailed images of fast-ion redistribution at instabilities are obtained. Qualitative and quantitative models relate the measured FIDA signals to the fast-ion distribution function. The first quantitative comparisons between theory and experiment found excellent agreement in beam-heated magnetohydrodynamics (MHD)-quiescent plasmas. FIDA diagnostics are now in operation at magnetic-fusion facilities worldwide. They are used to study fast-ion acceleration by ion cyclotron heating, to detect fast-ion transport by MHD modes and microturbulence, and to study fast-ion driven instabilities. PMID- 21033921 TI - A tangentially viewing fast ion D-alpha diagnostic for NSTX. AB - A second fast ion D-alpha (FIDA) installation is planned at NSTX to complement the present perpendicular viewing FIDA diagnostics. Following the present diagnostic scheme, the new diagnostic will consist of two instruments: a spectroscopic diagnostic that measures fast ion spectra and profiles at 16 radial points with 5-10 ms resolution and a system that uses a band pass filter and photomultiplier to measure changes in FIDA light with 50 kHz sampling rate. The new pair of FIDA instruments will view the heating beams tangentially. The viewing geometry minimizes spectral contamination by beam emission or edge sources of background emission. The improved velocity-space resolution will provide detailed information about neutral-beam current drive and about fast ion acceleration and transport by injected radio frequency waves and plasma instabilities. PMID- 21033922 TI - Measurements of the internal magnetic field using the B-Stark motional Stark effect diagnostic on DIII-D (inivited). AB - Results are presented from the B-Stark diagnostic installed on the DIII-D tokamak. This diagnostic provides measurements of the magnitude and direction of the internal magnetic field. The B-Stark system is a version of a motional Stark effect (MSE) diagnostic based on the relative line intensities and spacing of the Stark split D(alpha) emission from injected neutral beams. This technique may have advantages over MSE polarimetry based diagnostics in future devices, such as the ITER. The B-Stark diagnostic technique and calibration procedures are discussed. The system is shown to provide accurate measurements of B(theta)/B(T) and ?B? over a range of plasma conditions. Measurements have been made with toroidal fields in the range of 1.2-2.1 T, plasma currents in the range 0.5-2.0 MA, densities between 1.7 and 9.0*10(19) m(-3), and neutral beam voltages between 50 and 81 keV. The viewing direction and polarization dependent transmission properties of the collection optics are found using an in situ beam into gas calibration. These results are compared to values found from plasma equilibrium reconstructions and the MSE polarimetry system on DIII-D. PMID- 21033923 TI - Spectroscopic measurement of ion temperature and ion velocity distributions in the flux-coil generated FRC. AB - One aim of the flux-coil generated field reversed configuration at Tri Alpha Energy (TAE) is to establish the plasma where the ion rotational energy is greater than the ion thermal energy. To verify this, an optical diagnostic was developed to simultaneously measure the Doppler velocity-shift and line broadening using a 0.75 m, 1800 groves/mm, spectrometer. The output spectrum is magnified and imaged onto a 16-channel photomultiplier tube (PMT) array. The individual PMT outputs are coupled to high-gain, high-frequency, transimpedance amplifiers, providing fast-time response. The Doppler spectroscopy measurements, along with a survey spectrometer and photodiode-light detector, form a suite of diagnostics that provide insights into the time evolution of the plasma-ion distribution and current when accelerated by an azimuthal-electric field. PMID- 21033924 TI - High-throughput accurate-wavelength lens-based visible spectrometer. AB - A scanning visible spectrometer has been prototyped to complement fixed wavelength transmission grating spectrometers for charge exchange recombination spectroscopy. Fast f/1.8 200 mm commercial lenses are used with a large 2160 mm( 1) grating for high throughput. A stepping-motor controlled sine drive positions the grating, which is mounted on a precision rotary table. A high-resolution optical encoder on the grating stage allows the grating angle to be measured with an absolute accuracy of 0.075 arc sec, corresponding to a wavelength error <=0.005 A. At this precision, changes in grating groove density due to thermal expansion and variations in the refractive index of air are important. An automated calibration procedure determines all the relevant spectrometer parameters to high accuracy. Changes in bulk grating temperature, atmospheric temperature, and pressure are monitored between the time of calibration and the time of measurement to ensure a persistent wavelength calibration. PMID- 21033925 TI - High accuracy wavelength calibration for a scanning visible spectrometer. AB - Spectroscopic applications for plasma velocity measurements often require wavelength accuracies <=0.2 A. An automated calibration, which is stable over time and environmental conditions without the need to recalibrate after each grating movement, was developed for a scanning spectrometer to achieve high wavelength accuracy over the visible spectrum. This method fits all relevant spectrometer parameters using multiple calibration spectra. With a stepping-motor controlled sine drive, an accuracy of ~0.25 A has been demonstrated. With the addition of a high resolution (0.075 arc sec) optical encoder on the grating stage, greater precision (~0.005 A) is possible, allowing absolute velocity measurements within ~0.3 km/s. This level of precision requires monitoring of atmospheric temperature and pressure and of grating bulk temperature to correct for changes in the refractive index of air and the groove density, respectively. PMID- 21033926 TI - Deuterium velocity and temperature measurements on the DIII-D tokamak. AB - Newly installed diagnostic capabilities on the DIII-D tokamak [J. L. Luxon, Nucl. Fusion 46, 6114 (2002)] enable the measurement of main ion (deuterium) velocity and temperature by charge exchange recombination spectroscopy. The uncertainty in atomic physics corrections for determining the velocity is overcome by exploiting the geometrical dependence of the apparent velocity on the viewing angle with respect to the neutral beam. PMID- 21033927 TI - Vacuum ultraviolet impurity spectroscopy on the Alcator C-Mod tokamak. AB - Vacuum ultraviolet spectroscopy is used on the Alcator C-Mod tokamak to study the physics of impurity transport and provide feedback on impurity levels to assist experimental operations. Sputtering from C-Mod's all metal (Mo+W) plasma facing components and ion cyclotron range of frequency antenna and vessel structures (sources for Ti, Fe, Cu, and Ni), the use of boronization for plasma surface conditioning and Ar, Ne, or N(2) gas seeding combine to provide a wealth of spectroscopic data from low-Z to high-Z. Recently, a laser blow-off impurity injector has been added, employing CaF(2) to study core and edge impurity transport. One of the primary tools used to monitor the impurities is a 2.2 m Rowland circle spectrometer utilizing a Reticon array fiber coupled to a microchannel plate. With a 600 lines/mm grating the 8020 keV bremsstrahlung emission measured with the time integrated FFLEX broadband spectrometer. New high energy (>200 keV) time resolved channels were added to infer the generated >170 keV hot electrons that can cause ignition capsule preheat. First hot electron measurements in near ignition scaled Hohlraums heated by 96-192 NIF laser beams are presented. PMID- 21033966 TI - Target diagnostic control system implementation for the National Ignition Facility (invited). AB - The extreme physics of targets shocked by NIF's 192-beam laser is observed by a diverse suite of diagnostics. Many diagnostics are being developed by collaborators at other sites, but ad hoc controls could lead to unreliable and costly operations. A diagnostic control system (DCS) framework for both hardware and software facilitates development and eases integration. Each complex diagnostic typically uses an ensemble of electronic instruments attached to sensors, digitizers, cameras, and other devices. In the DCS architecture each instrument is interfaced to a low-cost WINDOWS XP processor and JAVA application. Each instrument is aggregated with others as needed in the supervisory system to form an integrated diagnostic. The JAVA framework provides data management, control services, and operator graphical user interface generation. DCS instruments are reusable by replication with reconfiguration for specific diagnostics in extensible markup language. Advantages include minimal application code, easy testing, and high reliability. Collaborators save costs by assembling diagnostics with existing DCS instruments. This talk discusses target diagnostic instrumentation used on NIF and presents the DCS architecture and framework. PMID- 21033967 TI - First real-time detection of surface dust in a tokamak. AB - The first real-time detection of surface dust inside a tokamak was made using an electrostatic dust detector. A fine grid of interlocking circuit traces was installed in the NSTX vessel and biased to 50 V. Impinging dust particles created a temporary short circuit and the resulting current pulse was recorded by counting electronics. The techniques used to increase the detector sensitivity by a factor of *10,000 to match NSTX dust levels while suppressing electrical pickup are presented. The results were validated by comparison to laboratory measurements, by the null signal from a covered detector that was only sensitive to pickup, and by the dramatic increase in signal when Li particles were introduced for wall conditioning purposes. PMID- 21033968 TI - Pulse shape measurements using single shot-frequency resolved optical gating for high energy (80 J) short pulse (600 fs) laser. AB - Relevant to laser based electron/ion accelerations, a single shot second harmonic generation frequency resolved optical gating (FROG) system has been developed to characterize laser pulses (80 J, ~600 fs) incident on and transmitted through nanofoil targets, employing relay imaging, spatial filter, and partially coated glass substrates to reduce spatial nonuniformity and B-integral. The device can be completely aligned without using a pulsed laser source. Variations of incident pulse shape were measured from durations of 613 fs (nearly symmetric shape) to 571 fs (asymmetric shape with pre- or postpulse). The FROG measurements are consistent with independent spectral and autocorrelation measurements. PMID- 21033969 TI - Residual gas analysis for long-pulse, advanced tokamak operation. AB - A shielded residual gas analyzer (RGA) system on Tore Supra can function during plasma operation and is set up to monitor the composition of the neutral gas in one of the pumping ducts of the toroidal pumped limited. This "diagnostic RGA" has been used in long-pulse (up to 6 min) discharges for continuous monitoring of up to 15 masses simultaneously. Comparison of the RGA-measured evolution of the H(2)/D(2) isotopic ratio in the exhaust gas to that measured by an energetic neutral particle analyzer in the plasma core provides a way to monitor the evolution of particle balance. RGA monitoring of corrective H(2) injection to maintain proper minority heating is providing a database for improved ion cyclotron resonance heating, potentially with RGA-base feedback control. In very long pulses (>4 min) absence of significant changes in the RGA-monitored, hydrocarbon particle pressures is an indication of proper operation of the actively cooled, carbon-based plasma facing components. Also H(2) could increase due to thermodesorption of overheated plasma facing components. PMID- 21033970 TI - A Hall sensor array for internal current profile constraint. AB - Measurements of the internal distribution of B in magnetically confined plasmas are required to obtain current profiles via equilibrium reconstruction with sufficient accuracy to challenge stability theory. A 16-channel linear array of InSb Hall effect sensors with 7.5 mm spatial resolution has been constructed to directly measure internal B(z)(R,t) for determination of J(psi,t) associated with edge-localized peeling mode instabilities in the Pegasus Toroidal Experiment. The diagnostic is mounted in an electrically isolated vacuum assembly which presents a slim, cylindrical profile (~1 cm outside diameter) to the plasma using graphite as a low-Z plasma facing component. Absolute calibration of the sensors is determined via in situ cross-calibration against existing magnetic pickup coils. Present channel sensitivities are of order of 0.25 mT. Internal measurements with bandwidth of <=25 kHz have been obtained without measurable plasma perturbation. They resolve n=1 internal magnetohydrodynamics and indicate systematic variation in J(psi) under different stability conditions. PMID- 21033971 TI - Simulated plasma facing component measurements for an in situ surface diagnostic on Alcator C-Mod. AB - The ideal in situ plasma facing component (PFC) diagnostic for magnetic fusion devices would perform surface element and isotope composition measurements on a shot-to-shot (~10 min) time scale with ~1 MUm depth and ~1 cm spatial resolution over large areas of PFCs. To this end, the experimental adaptation of the customary laboratory surface diagnostic--nuclear scattering of MeV ions--to the Alcator C-Mod tokamak is being guided by ACRONYM, a Geant4 synthetic diagnostic. The diagnostic technique and ACRONYM are described, and synthetic measurements of film thickness for boron-coated PFCs are presented. PMID- 21033972 TI - Characterization of a linear device developed for research on advanced plasma imaging and dynamics. AB - Within the scope of long term research on imaging diagnostics for steady-state plasmas and understanding of edge plasma physics through diagnostics with conventional spectroscopic methods, we have constructed a linear electron cyclotron resonance (ECR) plasma device named Research on Advanced Plasma Imaging and Dynamics (RAPID). It has a variety of axial magnetic field profiles provided by eight water-cooled magnetic coils and two dc power supplies. The positions of the magnetic coils are freely adjustable along the axial direction and the power supplies can be operated with many combinations of electrical wiring to the coils. Here, a 6 kW 2.45 GHz magnetron is used to produce steady-state hydrogen, helium, and argon plasmas with central magnetic fields of 875 and/or 437.5 G (second harmonic). In order to achieve the highest possible plasma performance within the limited input parameters, wall conditioning experiments were carried out. Chamber bake-out was achieved with heating coils that were wound covering the vessel, and long-pulse electron cyclotron heating discharge cleaning was also followed after 4 days of bake-out. A uniform bake-out temperature (150 degrees C) was achieved by wrapping the vessel in high temperature thermal insulation textile and by controlling the heating coil current using a digital control system. The partial pressure changes were observed using a residual gas analyzer, and a total system pressure of 5*10(-8) Torr was finally reached. Diagnostic systems including a millimeter-wave interferometer, a high resolution survey spectrometer, a Langmuir probe, and an ultrasoft x-ray detector were used to provide the evidence that the plasma performance was improved as we desired. In this work, we present characterization of the RAPID device for various system conditions and configurations. PMID- 21033973 TI - Engineering and manufacturing of ITER first mirror mock-ups. AB - Most of the ITER optical diagnostics aiming at viewing and monitoring plasma facing components will use in-vessel metallic mirrors. These mirrors will be exposed to a severe plasma environment and lead to an important tradeoff on their design and manufacturing. As a consequence, investigations are carried out on diagnostic mirrors toward the development of optimal and reliable solutions. The goals are to assess the manufacturing feasibility of the mirror coatings, evaluate the manufacturing capability and associated performances for the mirrors cooling and polishing, and finally determine the costs and delivery time of the first prototypes with a diameter of 200 and 500 mm. Three kinds of ITER candidate mock-ups are being designed and manufactured: rhodium films on stainless steel substrate, molybdenum on TZM substrate, and silver films on stainless steel substrate. The status of the project is presented in this paper. PMID- 21033974 TI - Heavy ion beam probe operation in time varying equilibria of improved confinement reversed field pinch discharges. AB - Operation of a heavy ion beam probe (HIBP) on a reversed field pinch is unique from other toroidal applications because the magnetic field is more temporal and largely produced by plasma current. Improved confinement, produced through the transient application of a poloidal electric field which leads to a reduction of dynamo activity, exhibits gradual changes in equilibrium plasma quantities. A consequence of this is sweeping of the HIBP trajectories by the dynamic magnetic field, resulting in motion of the sample volume. In addition, the plasma potential evolves with the magnetic equilibrium. Measurement of the potential as a function of time is thus a combination of temporal changes of the equilibrium and motion of the sample volume. A frequent additional complication is a nonideal balance of ion current on the detectors resulting from changes in the beam trajectory (magnetic field) and energy (plasma potential). This necessitates use of data selection criteria. Nevertheless, the HIBP on the Madison Symmetric Torus has acquired measurements as a function of time throughout improved confinement. A technique developed to infer the potential in the improved confinement reversed field pinch from HIBP data in light of the time varying plasma equilibrium will be discussed. PMID- 21033975 TI - Synchronization of Thomson scattering measurements on MAST using an FPGA based "Smart" trigger unit. AB - The MAST Thomson scattering diagnostic has recently been upgraded to make electron density and temperature measurements at 130 points across the 1.5 m diameter of the plasma. The new system is able to take 240 measurements per second using eight Nd:YAG lasers, each running at 30 Hz. The exact firing time of these lasers is adjusted with 100 ns precision using a field programmable gate array based trigger unit. Trigger pulses are produced to fire the lamps of all lasers and the Q switches with the appropriate delay depending on the warm-up status. The lasers may be fired in rapid bursts so as to achieve a high temporal resolution over eight points separated down to the microsecond level. This trigger unit receives optical trigger events and signals from external sources, allowing the trigger sequences to be resynchronized to the start of the plasma pulse and further events during the shot such as the entry of a fuelling pellet or randomly occurring plasma events. This resynchronization of the laser firing sequence allows accurate and reproducible measurements of fast plasma phenomena. PMID- 21033976 TI - Interpretation and implementation of an ion sensitive probe as a plasma potential diagnostic. AB - An ion sensitive probe (ISP) is developed as a robust diagnostic for measuring plasma potentials (Phi(P)) in magnetized plasmas. The ISP relies on the large difference between the ion and electron gyroradii (rho(i)/rho(e)~60) to reduce the electron collection at a collector recessed behind a separately biased wall distance ~rho(i). We develop a new ISP method to measure the plasma potential that is independent of the precise position and shape of the collector. Phi(P) is found as the wall potential when charged current to the probe collector vanishes during the voltage sweep. The plasma potentials obtained from the ISP match Phi(P) measured with an emissive probe over a wide range of plasma conditions in a small magnetized plasma. PMID- 21033977 TI - Diagnostics for ion beam driven high energy density physics experiments. AB - Intense beams of heavy ions are capable of heating volumetric samples of matter to high energy density. Experiments are performed on the resulting warm dense matter (WDM) at the NDCX-I ion beam accelerator. The 0.3 MeV, 30 mA K(+) beam from NDCX-I heats foil targets by combined longitudinal and transverse neutralized drift compression of the ion beam. Both the compressed and uncompressed parts of the NDCX-I beam heat targets. The exotic state of matter (WDM) in these experiments requires specialized diagnostic techniques. We have developed a target chamber and fielded target diagnostics including a fast multichannel optical pyrometer, optical streak camera, laser Doppler-shift interferometer (Velocity Interferometer System for Any Reflector), beam transmission diagnostics, and high-speed gated cameras. We also present plans and opportunities for diagnostic development and a new target chamber for NDCX-II. PMID- 21033978 TI - New field programmable gate array-based image-oriented acquisition and real-time processing applied to plasma facing component thermal monitoring. AB - During operation of present fusion devices, the plasma facing components (PFCs) are exposed to high heat fluxes. Understanding and preventing overheating of these components during long pulse discharges is a crucial safety issue for future devices like ITER. Infrared digital cameras interfaced with complex optical systems have become a routine diagnostic to measure surface temperatures in many magnetic fusion devices. Due to the complexity of the observed scenes and the large amount of data produced, the use of high computational performance hardware for real-time image processing is then mandatory to avoid PFC damages. At Tore Supra, we have recently made a major upgrade of our real-time infrared image acquisition and processing board by the use of a new field programmable gate array (FPGA) optimized for image processing. This paper describes the new possibilities offered by this board in terms of image calibration and image interpretation (abnormal thermal events detection) compared to the previous system. PMID- 21033979 TI - Magnetic diagnostics for equilibrium reconstructions in the presence of nonaxisymmetric eddy current distributions in tokamaks (invited). AB - The lithium tokamak experiment (LTX) is a modest-sized spherical tokamak (R(0)=0.4 m and a=0.26 m) designed to investigate the low-recycling lithium wall operating regime for magnetically confined plasmas. LTX will reach this regime through a lithium-coated shell internal to the vacuum vessel, conformal to the plasma last-closed-flux surface, and heated to 300-400 degrees C. This structure is highly conductive and not axisymmetric. The three-dimensional nature of the shell causes the eddy currents and magnetic fields to be three-dimensional as well. In order to analyze the plasma equilibrium in the presence of three dimensional eddy currents, an extensive array of unique magnetic diagnostics has been implemented. Sensors are designed to survive high temperatures and incidental contact with lithium and provide data on toroidal asymmetries as well as full coverage of the poloidal cross-section. The magnetic array has been utilized to determine the effects of nonaxisymmetric eddy currents and to model the start-up phase of LTX. Measurements from the magnetic array, coupled with two dimensional field component modeling, have allowed a suitable field null and initial plasma current to be produced. For full magnetic reconstructions, a three dimensional electromagnetic model of the vacuum vessel and shell is under development. PMID- 21033980 TI - Diagnostics for the plasma liner experiment. AB - The goal of the Plasma Liner Experiment (PLX) is to explore and demonstrate the feasibility of forming imploding spherical "plasma liners" via merging high Mach number plasma jets to reach peak liner pressures of ~0.1 Mbar using ~1.5 MJ of initial stored energy. Such a system would provide HED plasmas for a variety of fundamental HEDLP, laboratory astrophysics, and materials science studies, as well as a platform for experimental validation of rad-hydro and rad-MHD simulations. It could also prove attractive as a potential standoff driver for magnetoinertial fusion. Predicted parameters from jet formation to liner stagnation cover a large range of plasma density and temperature, varying from n(i)~10(16) cm(-3), T(e)~T(i)~1 eV at the plasma gun mouth to n(i)>10(19) cm(-3), T(e)~T(i)~0.5 keV at stagnation. This presents a challenging problem for the plasma diagnostics suite which will be discussed. PMID- 21033981 TI - Improved calibration technique of the infrared imaging bolometer using ultraviolet light-emitting diodes. AB - The technique used until recently utilizing the Ne-He laser for imaging bolometer foils calibration [B. J. Peterson et al., J. Plasma Fusion Res. 2, S1018 (2007)] has showed several issues. The method was based on irradiation of 1 cm spaced set of points on a foil by the laser beam moved by set of mirrors. Issues were the nonuniformity of laser power due to the vacuum window transmission nonuniformity and high reflection coefficient for the laser. Also, due to the limited infrared (IR) window size, it was very time consuming. The new methodology uses a compact ultraviolet (uv) light-emitting diodes installed inside the vacuum chamber in a fixed position and the foil itself will be moved in the XY directions by two vacuum feedthroughs. These will help to avoid the above mentioned issues due to lack of a vacuum window, fixed emitters, higher uv power absorption, and a fixed IR camera position. PMID- 21033982 TI - High density Langmuir probe array for NSTX scrape-off layer measurements under lithiated divertor conditions. AB - A high density Langmuir probe array has been developed for measurements of scrape off layer parameters in NSTX. Relevant scale lengths for heat and particle fluxes are 1-5 cm. Transient edge plasma events can occur on a time scale of several milliseconds, and the duration of a typical plasma discharge is ~1 s. The array consists of 99 individual electrodes arranged in three parallel radial rows to allow both swept and triple-probe operation and is mounted in a carbon tile located in the lower outer divertor of NSTX between two segments of the newly installed liquid lithium divertor. Initial swept probe results tracking the outer strike point through probe flux measurements are presented. PMID- 21033983 TI - Accurate and reliable image classification by using conformal predictors in the TJ-II Thomson scattering. AB - The charge-coupled device camera of the TJ-II Thomson scattering (TS) can capture five different classes of images. Typically, different data processing is performed depending on the kind of image that is acquired. The procedure can be automated to recognize the type of image. To this end, machine learning methods (MLM) are applied. However, usually, MLM classify without confidence estimates. An image classifier based on conformal predictors has been developed for the TJ II TS. It provides a couple of indicators (confidence and credibility) for each classification that measures the accuracy and reliability of the prediction. Results achieve success rates of about 97%. The implemented classifier is valid for any kind of images. PMID- 21033984 TI - A compact and continuously driven supersonic plasma and neutral source. AB - A compact and repetitively driven plasma source has been developed by utilizing a magnetized coaxial plasma gun (MCPG) for diagnostics requiring deep penetration of a large amount of neutral flux. The system consists of a MCPG 95mm in length with a DN16 ConFlat connection port and an insulated gate bipolar transistor (IGBT) inverter power unit. The power supply consists of an array of eight IGBT units and is able to switch the discharge on and off at up to 10 kV and 600 A with a maximum repetitive frequency of 10 kHz. Multiple short duration discharge pulses maximize acceleration efficiency of the plasmoid. In the case of a 10 kHz operating frequency, helium-plasmoids in the velocity range of 20 km/s can be achieved. PMID- 21033985 TI - Wall reflection issues for optical diagnostics in fusion devices. AB - The problem of light reflection has been raised as a high priority issue for optical diagnostics in next step fusion devices where metallic wall environment will generate significant perturbations in the diagnostics measurements. Tore Supra is a large size tokamak equipped with water-cooled stainless-steel panels used to sustain the plasma long shot radiations. These panels are highly reflective and affect significantly optical systems. In particular, we show that the infrared imaging diagnostic, which surveys the plasma facing component surface temperature for safety purposes, can give incorrect information due to reflected light coming from the bottom limiter. In the visible range, motional Stark effect and Zeff measurements experience important drifts during the plasma heating phases due to parasitic light coming from the limiter, but also from the plasma itself when the viewing lines are facing the reflecting walls. In the next step fusion devices such as ITER, the possibility to use optical measurements needs to be accessed by a modeling of the diagnostic light in its machine environment and the development of new techniques of online correction. PMID- 21033986 TI - Algorithm for precision subsample timing between Gaussian-like pulses. AB - Moderately priced oscilloscopes available for the NIF power sensors and target diagnostics have 6 GHz bandwidths at 20-25 Gsamples/s (40 ps sample spacing). Some NIF experiments require cross timing between instruments be determined with accuracy better than 30 ps. A simple analysis algorithm for Gaussian-like pulses such as the 100-ps-wide NIF timing fiducial can achieve single-event cross-timing precision of 1 ps (1/50 of the sample spacing). The midpoint-timing algorithm is presented along with simulations that show why the technique produces good timing results. Optimum pulse width is found to be ~2.5 times the sample spacing. Experimental measurements demonstrate use of the technique and highlight the conditions needed to obtain optimum timing performance. PMID- 21033987 TI - Irradiation tests of ITER candidate Hall sensors using two types of neutron spectra. AB - We report on irradiation tests of InSb based Hall sensors at two irradiation facilities with two distinct types of neutron spectra. One was a fission reactor neutron spectrum with a significant presence of thermal neutrons, while another one was purely fast neutron field. Total neutron fluence of the order of 10(16) cm(-2) was accumulated in both cases, leading to significant drop of Hall sensor sensitivity in case of fission reactor spectrum, while stable performance was observed at purely fast neutron spectrum. This finding suggests that performance of this particular type of Hall sensors is governed dominantly by transmutation. Additionally, it further stresses the need to test ITER candidate Hall sensors under neutron flux with ITER relevant spectrum. PMID- 21033988 TI - Operation Request Gatekeeper: a software system for remote access control of diagnostic instruments in fusion experiments. AB - Tokamak diagnostic settings are repeatedly modified to meet the changing needs of each experiment. Enabling the remote diagnostic control has significant challenges due to security and efficiency requirements. The Operation Request Gatekeeper (ORG) is a software system that addresses the challenges of remotely but securely submitting modification requests. The ORG provides a framework for screening all the requests before they enter the secure machine zone and are executed by performing user authentication and authorization, grammar validation, and validity checks. A prototype ORG was developed for the ITER CODAC that satisfies their initial requirements for remote request submission and has been tested with remote control of the KSTAR Plasma Control System. This paper describes the software design principles and implementation of ORG as well as worldwide test results. PMID- 21033989 TI - New printed circuit boards magnetic coils in the vacuum vessel of J-TEXT tokamak for position measurement. AB - Four sets of magnetic diagnostic coils, which are printed on machinable ceramic printed circuit boards (PCB), are designed, fabricated, installed, and tested in the Joint Texas Experimental Tokamak (J-TEXT) vacuum vessel for detecting the plasma radial and vertical displacements relative to the geometric center of the vacuum vessel in Ohmic discharges. Each coordinate is determined by a pair of variable cross-section Rogowski and saddle coils, which measure the tangential and normal magnetic fields (relative to the coil surface). These coils are suitable for mass production and offer advantages in vacuum compatibility and temperature tolerance that are important for J-TEXT. Position measurements using PCB coils are compared with those from soft x-ray image system and match the position well. PMID- 21033990 TI - Event recognition using signal spectrograms in long pulse experiments. AB - As discharge duration increases, real-time complex analysis of the signal becomes more important. In this context, data acquisition and processing systems must provide models for designing experiments which use event oriented plasma control. One example of advanced data analysis is signal classification. The off-line statistical analysis of a large number of discharges provides information to develop algorithms for the determination of the plasma parameters from measurements of magnetohydrodinamic waves, for example, to detect density fluctuations induced by the Alfven cascades using morphological patterns. The need to apply different algorithms to the signals and to address different processing algorithms using the previous results necessitates the use of an event based experiment. The Intelligent Test and Measurement System platform is an example of architecture designed to implement distributed data acquisition and real-time processing systems. The processing algorithm sequence is modeled using an event-based paradigm. The adaptive capacity of this model is based on the logic defined by the use of state machines in SCXML. The Intelligent Test and Measurement System platform mixes a local multiprocessing model with a distributed deployment of services based on Jini. PMID- 21033991 TI - The use of bayesian inversion to resolve plasma equilibrium. AB - Recently, bayesian probability theory has been used at a number of experiments to fold uncertainties and interdependencies in the diagnostic data and forward models, together with prior knowledge of the state of the plasma, to increase accuracy of inferred physics variables. A new probabilistic framework, MINERVA, based on bayesian graphical models, has been used at JET and W7-AS to yield predictions of internal magnetic structure. A feature of the framework is the bayesian inversion for poloidal magnetic flux without the need for an explicit equilibrium assumption. Building on this, we discuss results from a new project to develop bayesian inversion tools that aim to (1) distinguish between competing equilibrium theories, which capture different physics, using the MAST spherical tokamak, and (2) test the predictions of MHD theory, particularly mode structure, using the H-1 Heliac. Specifically, we report on correction of the motional Stark effect, pickup coils, flux-loop constrained bayesian inferred equilibrium for varying toroidal flux. PMID- 21033992 TI - First results of the resistive bolometers on KSTAR. AB - The resistive bolometers have been successfully installed in the midplane of L port in Korea Superconducting Tokamak Advanced Research (KSTAR) device. The spatial and temporal resolutions, 4.5 cm and ~1 kHz, respectively, enable us to measure the radial profile of the total radiated power from magnetically confined plasma at a high temperature through radiation and neutral particles. The radiated power was measured at all shots. Even at low plasma current, the bolometer signal was detectable. The electron cyclotron resonance heating (ECH) has been used in tokamak for ECH assisted start-up and plasma control by local heating and current drive. The detectors of resistive bolometer, near the antenna of ECH, are affected by electron cyclotron wave. The tomographic reconstruction, using the Phillips-Tikhonov regularization method, will be carried out for a major radial profile of the radiation emissivity of the circular cross-section plasma. PMID- 21033993 TI - Magnetically insulated baffled probe for real-time monitoring of equilibrium and fluctuating values of space potentials, electron and ion temperatures, and densities. AB - By restricting the electron-collection area of a cold Langmuir probe compared to the ion-collection area, the probe floating potential can become equal to the space potential, and thus conveniently monitored, rather than to a value shifted from the space potential by an electron-temperature-dependent offset, i.e., the case with an equal-collection-area probe. This design goal is achieved by combining an ambient magnetic field in the plasma with baffles, or shields, on the probe, resulting in species-selective magnetic insulation of the probe collection area. This permits the elimination of electron current to the probe by further adjustment of magnetic insulation which results in an ion-temperature dependent offset when the probe is electrically floating. Subtracting the floating potential of two magnetically insulated baffled probes, each with a different degree of magnetic insulation, enables the electron or ion temperature to be measured in real time. PMID- 21033994 TI - Biasing, acquisition, and interpretation of a dense Langmuir probe array in NSTX. AB - A dense array of 99 Langmuir probes has been installed in the lower divertor region of the National Spherical Torus Experiment (NSTX). This array is instrumented with a system of electronics that allows flexibility in the choice of probes to bias as well as the type of measurement (including standard swept, single probe, triple probe, and operation as passive floating potential and scrape-off-layer SOL current monitors). The use of flush-mounted probes requires careful interpretation. The time dependent nature of the SOL makes swept-probe traces difficult to interpret. To overcome these challenges, the single- and triple-Langmuir probe signals are used in complementary fashion to determine the temperature and density at the probe location. A comparison to midplane measurements is made. PMID- 21033995 TI - Diagnostics design for steady-state operation of the Wendelstein 7-X stellarator. AB - The status of the diagnostic developments for the quasistationary operable stellarator Wendelstein 7-X (maximum pulse length of 30 min at 10 MW ECRH heating at 140 GHz) will be reported on. Significant emphasis is being given to the issue of ECRH stray radiation shielding of in-vessel diagnostic components, which will be critical at high density operation requiring O2 and OXB heating. PMID- 21033996 TI - Design criteria of the bolometer diagnostic for steady-state operation of the W7 X stellarator. AB - A bolometric diagnostic system with features necessary for steady-state operation in the superconducting stellarator W7-X was designed. During a pulse length of 1800 s with an ECRH (electron cyclotron resonance heating) power of 10 MW, the components suffer not only from a large thermal load but also from stray radiation of the nonabsorbed isotropic microwaves. This paper gives an overview of the technical problems encountered during the design work and the solutions to individual problems to meet the special requirements in W7-X, e.g., component thermal protection, detector offset thermal drift suppression, as well as a microwave shielding technique. PMID- 21033997 TI - Defining the infrared systems for ITER. AB - The International Thermonuclear Experimental Reactor will have wide angle viewing systems and a divertor thermography diagnostic, which shall provide infrared coverage of the divertor and large parts of the first wall surfaces with spatial and temporal resolution adequate for operational purposes and higher resolved details of the divertor and other areas for physics investigations. We propose specifications for each system such that they jointly respond to the requirements. Risk analysis driven priorities for future work concern mirror degradation, interfaces with other diagnostics, radiation damage to refractive optics, reflections, and the development of calibration and measurement methods for varying optical and thermal target properties. PMID- 21033998 TI - Multichannel Langmuir probe for turbulence study in Heliotron J. AB - New multichannel Langmuir probe system was developed and installed to Heliotron J. The objective of the new probe is to characterize basic turbulence property and the resulting transport in advanced helical configuration. The probe developed here consists of four sets of triple probe and one pin for floating potential measurement. Initial experiments in neutral beam heating plasma were conducted and fluctuation profile of radial and poloidal electric fields and Reynolds stress were estimated. For precise evaluation of the electric fields and Reynolds stress, a technique to compensate radial change of tilt angle between probe array and magnetic surface was proposed and applied to the initial results obtained in edge region of Heliotron J where the complicated magnetic structure exists. PMID- 21033999 TI - Potential measurements with heavy ion beam probe system on LHD. AB - The heavy ion beam probe system in the Large Helical Device (LHD) was improved as follows. At first, the additional new sweeper was installed into the diagnostic port to extend the observable region. By using this sweeper, the potential profile was measured in a wider minor radius range than in previous experiments, in the case of outward shifted magnetic configuration of LHD. Next, the real time control system was installed to control the probe beam orbit for measuring the potential in plasma with large plasma current. In this system, a digital signal processor was used to control the probe beam in real time. The system worked well in the fixed position observation mode. In the sweeping mode for profile measurement, this control system became unstable. The details of this system and the experimental results are reported in this article. PMID- 21034000 TI - Hard x-ray transmission crystal spectrometer at the OMEGA-EP laser facility. AB - The transmission crystal spectrometer (TCS) is approved for taking data at the OMEGA-EP laser facility since 2009 and will be available for the OMEGA target chamber in 2010. TCS utilizes a Cauchois type cylindrically bent transmission crystal geometry with a source to crystal distance of 600 mm. Spectral images are recorded by image plates in four positions, one IP on the Rowland circle and three others at 200, 400, and 600 mm beyond the Rowland circle. An earlier version of TCS was used at LULI on experiments that determined the x-ray source size from spectral line broadening on one IP positioned behind the Rowland circle. TCS has recorded numerous backlighter spectra at EP for point projection radiography and for source size measurements. Hard x-ray source size can be determined from the source broadening of both K shell emission lines and from K absorption edges in the bremsstrahlung continuum, the latter being a new way to measure the spatial extent of the hard x-ray bremsstrahlung continuum. PMID- 21034001 TI - K-line spectra from tungsten heated by an intense pulsed electron beam. AB - The plasma-filled rod-pinch diode (PFRP) is an intense source of x-rays ideal for radiography of dense objects. In the PRFP megavoltage electrons from a pulsed discharge concentrate at the pointed end of a 1 mm diameter tapered tungsten rod. Ionization of this plasma might increase the energy of tungsten's Kalpha(1) fluorescence line, at 59.3182 keV, enough for the difference to be observed by a high-resolution Cauchois transmission crystal spectrograph. When the PFRP's intense hard bremsstrahlung is suppressed by the proper shielding, such an instrument gives excellent fluorescence spectra, albeit with as yet insufficient resolution to see any effect of tungsten's ionization. Higher resolution is possible with various straightforward upgrades that are feasible thanks to the radiation's high intensity. PMID- 21034002 TI - Soft x-ray continuum radiation transmitted through metallic filters: an analytical approach to fast electron temperature measurements. AB - A new set of analytic formulas describes the transmission of soft x-ray continuum radiation through a metallic foil for its application to fast electron temperature measurements in fusion plasmas. This novel approach shows good agreement with numerical calculations over a wide range of plasma temperatures in contrast with the solutions obtained when using a transmission approximated by a single-Heaviside function [S. von Goeler et al., Rev. Sci. Instrum. 70, 599 (1999)]. The new analytic formulas can improve the interpretation of the experimental results and thus contribute in obtaining fast temperature measurements in between intermittent Thomson scattering data. PMID- 21034003 TI - Streaked radiography measurements of convergent ablator performance (invited). AB - The velocity and remaining ablator mass of an imploding capsule are critical metrics for assessing the progress toward ignition of an inertially confined fusion experiment. These and other ablator rocket parameters have been measured using a single streaked x-ray radiograph. A regularization technique has been used to determine the ablator density profile rho(r) at each time step; moments of rho(r) then provide the areal density, average radius, and mass of the unablated, or remaining, ablator material, with the velocity determined from the time derivative of the average radius. The technique has been implemented on experiments at the OMEGA laser facility. PMID- 21034004 TI - X-ray spectroscopy of Cu impurities on NSTX and comparison with Z-pinch plasmas. AB - X-ray spectroscopy of mid-Z metal impurities is important in the study of tokamak plasmas and may reveal potential problems if their contribution to the radiated power becomes substantial. The analysis of the data from a high-resolution x-ray and extreme ultraviolet grating spectrometer, XEUS, installed on NSTX, was performed focused on a detailed study of x-ray spectra in the range 7-18 A. These spectra include not only commonly seen iron spectra but also copper spectra not yet employed as an NSTX plasma impurity diagnostic. In particular, the L-shell Cu spectra were modeled and predictions were made for identifying contributions from various Cu ions in different spectral bands. Also, similar spectra, but from much denser Cu plasmas produced on the UNR Z-pinch facility and collected using the convex-crystal spectrometer, were analyzed and compared with NSTX results. PMID- 21034005 TI - Spatially distributed scintillator arrays for diagnosing runaway electron transport and energy behavior in tokamaks. AB - We present details of a new bismuth germanate [Bi(4)Ge(3)O(12) (BGO)] scintillator array used to diagnose the transport and energy behavior of runaway electrons (REs) in DIII-D. BGO exhibits important properties for these compact detectors including high light yield which sufficiently excites photodiode detectors (8500 photons/MeV), high density and atomic numbers of constituent materials which maximizes sensitivity, and relative neutron blindness which minimizes complications in data interpretation. The detectors observe primarily hard x-ray radiation emitted in a forward beamed pattern by RE when they strike first wall materials or bulk ions and neutrals in the plasma, although we also address photoneutron signals. The arrangement of the array enables time resolved location of x-ray emission and associated asymmetries which help identify instabilities and confinement properties of RE. By shielding a subset of detectors with different thicknesses of lead, and with interpretative support of the code EGSNRC, we also measure RE energy, although due to the often distributed nature of RE strike points and the forward beamed character of emitted hard x rays, we restrict interpretation as a lower bound for RE energy. PMID- 21034006 TI - Spectroscopic modeling of an argon-doped shock-ignition implosion. AB - We present results from the spectral postprocessing of a one-dimensional hydrodynamic simulation of an argon-doped, warm-shell shock-ignition implosion with a detailed atomic and radiation physics model. The argon tracer is added to the deuterium filling in the core for diagnostic purposes. Spectral features in the emergent intensity distribution in the photon energy range of the argon K shell spectrum that have potential for diagnostic application are discussed. PMID- 21034007 TI - An upgraded x-ray spectroscopy diagnostic on MST. AB - An upgraded x-ray spectroscopy diagnostic is used to measure the distribution of fast electrons in MST and to determine Z(eff) and the particle diffusion coefficient D(r). A radial array of 12 CdZnTe hard-x-ray detectors measures 10 150 keV Bremsstrahlung from fast electrons, a signature of reduced stochasticity and improved confinement in the plasma. A new Si soft-x-ray detector measures 2 10 keV Bremsstrahlung from thermal and fast electrons. The shaped output pulses from both detector types are digitized and the resulting waveforms are fit with Gaussians to resolve pileup and provide good time and energy resolution. Lead apertures prevent detector saturation and provide a well-known etendue, while lead shielding prevents pickup from stray x-rays. New Be vacuum windows transmit >2 keV x-rays, and additional Al and Be filters are sometimes used to reduce low energy flux for better resolution at higher energies. Measured spectra are compared to those predicted by the Fokker-Planck code CQL3D to deduce Z(eff) and D(r). PMID- 21034008 TI - High energy photocathodes for laser fusion diagnostics. AB - Laser fusion experiments at the National Ignition Facility require time-resolved x-ray images of the ignition target self-emission. The photon energies are expected to be greater than 10 keV. Photoemission quantum yield measurement data and photoelectron energy spectrum data are presently unavailable in this photon energy range, but are essential in the design of x-ray imaging diagnostics. We developed an apparatus to measure the quantum efficiency of primary and secondary photoelectron emission and to estimate the energy spectrum of the secondary photoelectrons. The apparatus has been tested using photon energies less than 10 keV to allow comparisons with prior work. A method for preparing photocathodes with geometrically enhanced photoefficiency has been developed. PMID- 21034009 TI - Electronic measurement of microchannel plate pulse height distributions. AB - Microchannel plates are a central component of the x-ray framing cameras used as analog imagers in many plasma experiment diagnostic systems. The microchannel plate serves as an amplifying element, increasing the electronic signal from incident radiation by factors of 10(3)-10(5), with a broad pulse-height distribution. Seeking to optimize the photon-to-electron conversion efficiency and noise distribution of x-ray cameras, we will characterize the pulse-height distribution of the electron output from a single microchannel plate. Replacing the framing camera's phosphor-coated fiber optic screen with a charge-collection plate and coupling to a low-noise multichannel analyzer, we quantified the distribution in the total charge generated per photon event. The electronically measured pulse height distribution is used to estimate the signal-to-noise ratio of radiographic images from framing cameras. PMID- 21034010 TI - Asymmetrically cut crystal pair as x-ray magnifier for imaging at high intensity laser facilities. AB - The potential of an x-ray magnifier prepared from a pair of asymmetrically cut crystals is studied to explore high energy x-ray imaging capabilities at high intensity laser facilities. OMEGA-EP and NIF when irradiating mid and high Z targets can be a source of high-energy x-rays whose production mechanisms and use as backlighters are a subject of active research. This paper studies the properties and potential of existing asymmetric cut crystal pairs from the National Institute of Standards and Technology (NIST) built in a new enclosure for imaging x-ray sources. The technique of the x-ray magnifier has been described previously. This new approach is aimed to find a design that could be used at laser facilities by magnifying the x-ray source into a screen far away from the target chamber center, with fixed magnification defined by the crystals' lattice spacing and the asymmetry angles. The magnified image is monochromatic and the imaging wavelength is set by crystal asymmetry and incidence angles. First laboratory results are presented and discussed. PMID- 21034011 TI - Spatially resolved high-resolution x-ray spectroscopy of high-current plasma focus discharges. AB - Soft x-ray emission from a Mather-type plasma-focus device (PF-1000) operated at ~400 kJ was measured. The high density and temperature plasma were generated by the discharge in the deuterium-argon gas mixture in the modified (high-current) plasma-focus configuration. A spherically bent mica crystal spectrograph viewing the axial output of the pinch region was used to measure the x-ray spectra. Spatially resolved spectra including the characteristic x-ray lines of highly ionized Ar and continua were recorded by means of an x-ray film. The x-ray emission of PF-1000 device was studied at different areas of the pinch. PMID- 21034012 TI - Calibration of a microchannel plate based extreme ultraviolet grazing incident spectrometer at the Advanced Light Source. AB - We present the design and calibration of a microchannel plate based extreme ultraviolet spectrometer. Calibration was performed at the Advance Light Source (ALS) at the Lawrence Berkeley National Laboratory (LBNL). This spectrometer will be used to record the single shot spectrum of radiation emitted by the tapered hybrid undulator (THUNDER) undulator installed at the LOASIS GeV-class laser plasma-accelerator. The spectrometer uses an aberration-corrected concave grating with 1200 lines/mm covering 11-62 nm and a microchannel plate detector with a CsI coated photocathode for increased quantum efficiency in the extreme ultraviolet. A touch screen interface controls the grating angle, aperture size, and placement of the detector in vacuum, allowing for high-resolution measurements over the entire spectral range. PMID- 21034013 TI - Calibration of a high resolution grating soft x-ray spectrometer. AB - The calibration of the soft x-ray spectral response of a large radius of curvature, high resolution grating spectrometer (HRGS) with a back-illuminated charge-coupled device detector is reported. The instrument is cross-calibrated for the 10-50 A waveband at the Lawrence Livermore National Laboratory electron beam ion trap (EBIT) x-ray source with the EBIT calorimeter spectrometer. The HRGS instrument is designed for laser-produced plasma experiments and is important for making high dynamic range measurements of line intensities, line shapes, and x-ray sources. PMID- 21034014 TI - Measuring symmetry of implosions in cryogenic Hohlraums at the NIF using gated x ray detectors (invited). AB - Ignition of imploding inertial confinement capsules requires, among other things, controlling the symmetry with high accuracy and fidelity. We have used gated x ray imaging, with 10 MUm and 70 ps resolution, to detect the x-ray emission from the imploded core of symmetry capsules at the National Ignition Facility. The measurements are used to characterize the time dependent symmetry and the x-ray bang time of the implosion from two orthogonal directions. These measurements were one of the primary diagnostics used to tune the parameters of the laser and Hohlraum to vary the symmetry and x-ray bang time of the implosion of cryogenically cooled ignition scale deuterium/helium filled plastic capsules. Here, we will report on the successful measurements performed with up to 1.2 MJ of laser energy in a fully integrated cryogenics gas-filled ignition-scale Hohlraum and capsule illuminated with 192 smoothed laser beams. We will describe the technique, the accuracy of the technique, and the results of the variation in symmetry with tuning parameters, and explain how that set was used to predictably tune the implosion symmetry as the laser energy, the laser cone wavelength separation, and the Hohlraum size were increased to ignition scales. We will also describe how to apply that technique to cryogenically layered tritium-hydrogen deuterium capsules. PMID- 21034015 TI - Pulse-dilation enhanced gated optical imager with 5 ps resolution (invited). AB - A 5 ps gated framing camera was demonstrated using the pulse-dilation of a drifting electron signal. The pulse-dilation is achieved by accelerating a photoelectron derived information pulse with a time varying potential [R. D. Prosser, J. Phys. E 9, 57 (1976)]. The temporal dependence of the accelerating potential causes a birth time dependent axial velocity dispersion that spreads the pulse as it transits a drift region. The expanded pulse is then imaged with a conventional gated microchannel plate based framing camera and the effective gating time of the combined instrument is reduced over that of the framing camera alone. In the drift region, electron image defocusing in the transverse or image plane is prevented with a large axial magnetic field. Details of the unique issues associated with rf excited photocathodes were investigated numerically and a prototype instrument based on this principle was recently constructed. Temporal resolution of the instrument was measured with a frequency tripled femtosecond laser operating at 266 nm. The system demonstrated 20* temporal magnification and the results are presented here. X-ray image formation strategies and photometric calculations for inertial confinement fusion implosion experiments are also examined. PMID- 21034016 TI - Development of a time-resolved soft x-ray spectrometer for laser produced plasma experiments. AB - A 2400 lines/mm variable-spaced grating spectrometer has been used to measure soft x-ray emission (8-22 A) from laser-produced plasma experiments at Lawrence Livermore National Laboratory's Compact Multipulse Terrawatt (COMET) Laser Facility. The spectrometer was coupled to a Kentech x-ray streak camera to study the temporal evolution of soft x rays emitted from the back of the Mylar and the copper foils irradiated at 10(15) W/cm(2). The instrument demonstrated a resolving power of ~120 at 19 A with a time resolution of 31 ps. The time resolved copper emission spectrum was consistent with a photodiode monitoring the laser temporal pulse shape and indicated that the soft x-ray emission follows the laser heating of the target. The time and spectral resolutions of this diagnostic make it useful for studies of high temperature plasmas. PMID- 21034017 TI - Calibration of a flat field soft x-ray grating spectrometer for laser produced plasmas. AB - We have calibrated the x-ray response of a variable line spaced grating spectrometer, known as the VSG, at the Fusion and Astrophysics Data and Diagnostic Calibration Facility at the Lawrence Livermore National Laboratory (LLNL). The VSG has been developed to diagnose laser produced plasmas, such as those created at the Jupiter Laser Facility and the National Ignition Facility at LLNL and at both the Omega and Omega EP lasers at the University of Rochester's Laboratory for Laser Energetics. The bandwidth of the VSG spans the range of ~6 60 A. The calibration results presented here include the VSG's dispersion and quantum efficiency. The dispersion is determined by measuring the x rays emitted from the hydrogenlike and heliumlike ions of carbon, nitrogen, oxygen, neon, and aluminum. The quantum efficiency is calibrated to an accuracy of 30% or better by normalizing the x-ray intensities recorded by the VSG to those simultaneously recorded by an x-ray microcalorimeter spectrometer. PMID- 21034018 TI - Scaling studies with the dual crystal spectrometer at the OMEGA-EP laser facility. AB - The dual crystal spectrometer (DCS) is an approved diagnostic at the OMEGA and the OMEGA-EP laser facilities for the measurement of high energy x-rays in the 11 90 keV energy range, e.g., for verification of the x-ray spectrum of backlighter targets of point projection radiography experiments. DCS has two cylindrically bent transmission crystal channels with image plate detectors at distances behind the crystals close to the size of the respective Rowland circle diameters taking advantage of the focusing effect of the cylindrically bent geometry. DCS, with a source to crystal distance of 1.2 m, provides the required energy dispersion for simultaneous detection of x-rays in a low energy channel (11-45 keV) and a high energy channel (19-90 keV). A scaling study is described for varied pulse length with unchanged laser conditions (energy, focusing). The study shows that the Kalpha line intensity is not strongly dependent on the length of the laser pulse. PMID- 21034019 TI - The first measurements of soft x-ray flux from ignition scale Hohlraums at the National Ignition Facility using DANTE (invited). AB - The first 96 and 192 beam vacuum Hohlraum target experiments have been fielded at the National Ignition Facility demonstrating radiation temperatures up to 340 eV and fluxes of 20 TW/sr as viewed by DANTE representing an ~20 times flux increase over NOVA/Omega scale Hohlraums. The vacuum Hohlraums were irradiated with 2 ns square laser pulses with energies between 150 and 635 kJ. They produced nearly Planckian spectra with about 30+/-10% more flux than predicted by the preshot radiation hydrodynamic simulations. To validate these results, careful verification of all component calibrations, cable deconvolution, and software analysis routines has been conducted. In addition, a half Hohlraum experiment was conducted using a single 2 ns long axial quad with an irradiance of ~2*10(15) W/cm(2) for comparison with NIF Early Light experiments completed in 2004. We have also completed a conversion efficiency test using a 128-beam nearly uniformly illuminated gold sphere with intensities kept low (at 1*10(14) W/cm(2) over 5 ns) to avoid sensitivity to modeling uncertainties for nonlocal heat conduction and nonlinear absorption mechanisms, to compare with similar intensity, 3 ns OMEGA sphere results. The 2004 and 2009 NIF half-Hohlraums agreed to 10% in flux, but more importantly, the 2006 OMEGA Au Sphere, the 2009 NIF Au sphere, and the calculated Au conversion efficiency agree to +/-5% in flux, which is estimated to be the absolute calibration accuracy of the DANTEs. Hence we conclude that the 30+/-10% higher than expected radiation fluxes from the 96 and 192 beam vacuum Hohlraums are attributable to differences in physics of the larger Hohlraums. PMID- 21034020 TI - Development of a spatially resolving x-ray crystal spectrometer for measurement of ion-temperature (T(i)) and rotation-velocity (v) profiles in ITER. AB - Imaging x-ray crystal spectrometer (XCS) arrays are being developed as a US-ITER activity for Doppler measurement of T(i) and v profiles of impurities (W, Kr, and Fe) with ~7 cm (a/30) and 10-100 ms resolution in ITER. The imaging XCS, modeled after a prototype instrument on Alcator C-Mod, uses a spherically bent crystal and 2D x-ray detectors to achieve high spectral resolving power (E/dE>6000) horizontally and spatial imaging vertically. Two arrays will measure T(i) and both poloidal and toroidal rotation velocity profiles. The measurement of many spatial chords permits tomographic inversion for the inference of local parameters. The instrument design, predictions of performance, and results from C Mod are presented. PMID- 21034021 TI - The ITER core imaging x-ray spectrometer: x-ray calorimeter performance. AB - We describe the anticipated performance of an x-ray microcalorimeter instrument on ITER. As part of the core imaging x-ray spectrometer, the instrument will augment the imaging crystal spectrometers by providing a survey of the concentration of heavy ion plasma impurities in the core and possibly ion temperature values from the emission lines of different elemental ions located at various radial positions. PMID- 21034022 TI - Data processing of absorption spectra from photoionized plasma experiments at Z. AB - We discuss the processing of x-ray absorption spectra from photoionized plasma experiments at Z. The data was recorded with an imaging spectrometer equipped with two elliptically bent potassium acid phthalate (KAP) crystals. Both time integrated and time-resolved data were recorded. In both cases, the goal is to obtain the transmission spectra for quantitative analysis of plasma conditions. PMID- 21034023 TI - Spectroscopy of betatron radiation emitted from laser-produced wakefield accelerated electrons. AB - X-ray betatron radiation is produced by oscillations of electrons in the intense focusing field of a laser-plasma accelerator. These hard x-rays show promise for use in femtosecond-scale time-resolved radiography of ultrafast processes. However, the spectral characteristics of betatron radiation have only been inferred from filter pack measurements. In order to achieve higher resolution spectral information about the betatron emission, we used an x-ray charge-coupled device to record the spectrum of betatron radiation, with a full width at half maximum resolution of 225 eV. In addition, we have recorded simultaneous electron and x-ray spectra along with x-ray images that allow for a determination of the betatron emission source size, as well as differences in the x-ray spectra as a function of the energy spectrum of accelerated electrons. PMID- 21034024 TI - Experimental setup for tungsten transport studies at the NSTX tokamak. AB - Tungsten particles have been introduced into the National Spherical Torus Experiment (NSTX) in Princeton with the purpose to investigate the effects of tungsten injection on subsequent plasma discharges. An experimental setup for the study of tungsten particle transport is described where the particles are introduced into the tokamak using a modified particle dropper, otherwise used for lithium-powder injection. An initial test employing a grazing-incidence extreme ultraviolet spectrometer demonstrates that the tungsten-transport setup could serve to infer particle transport from the edge to the hot central plasmas of NSTX. PMID- 21034025 TI - X-ray crystal spectrometer for opacity measurements in the 8-18 A spectral range at the LULI laser facility. AB - An x-ray crystal spectrometer was built in order to measure opacities in the 8-18 A spectral range with an average spectral resolution of ~ 400. It has been successfully used at the LULI-2000 laser facility (See C. Sauteret, rapport LULI 2001, 88 (2002) at Ecole Polytechnique (France) to measure in the same experimental conditions the 2p-3d transitions of several elements with the neighboring atomic number Z: Fe, Ni, Cu, and Ge [G. Loisel et al., High Energy Density Phys. 5, 173 (2009)]. Hence, a spectrometer with a wide spectral range is needed. This spectrometer features two lines of sight. In this example, one line of sight looks through the sample and the other one is looking directly at the backlighter emission. Both are outfitted with a spherical condensing mirror. A TlAP crystal is used for spectral dispersion. Detection is made with an image plate Fuji BAS TR2025, which is sensitive to x rays. We present some experimental results showing the performances of this spectrometer. PMID- 21034026 TI - Objectives and layout of a high-resolution x-ray imaging crystal spectrometer for the large helical device. AB - A high-resolution x-ray imaging crystal spectrometer, whose concept was tested on NSTX and Alcator C-Mod, is being designed for the large helical device (LHD). This instrument will record spatially resolved spectra of helium-like Ar(16+) and will provide ion temperature profiles with spatial and temporal resolutions of <2 cm and >=10 ms, respectively. The spectrometer layout and instrumental features are largely determined by the magnetic field structure of LHD. The stellarator equilibrium reconstruction codes, STELLOPT and PIES, will be used for the tomographic inversion of the spectral data. PMID- 21034027 TI - Calculation of the Johann error for spherically bent x-ray imaging crystal spectrometers. AB - New x-ray imaging crystal spectrometers, currently operating on Alcator C-Mod, NSTX, EAST, and KSTAR, record spectral lines of highly charged ions, such as Ar(16+), from multiple sightlines to obtain profiles of ion temperature and of toroidal plasma rotation velocity from Doppler measurements. In the present work, we describe a new data analysis routine, which accounts for the specific geometry of the sightlines of a curved-crystal spectrometer and includes corrections for the Johann error to facilitate the tomographic inversion. Such corrections are important to distinguish velocity induced Doppler shifts from instrumental line shifts caused by the Johann error. The importance of this correction is demonstrated using data from Alcator C-Mod. PMID- 21034028 TI - Design and measurement of a Cu L-edge x-ray filter for free electron laser pumped x-ray laser experiments. AB - An inner-shell photoionized x-ray laser pumped by the Linac Coherent Light Source (LCLS) free electron laser has been proposed recently. The measurement of the on axis 849 eV Ne Kalpha laser and protection of the x-ray spectrometer from damage require attenuation of the 1 keV LCLS beam. An Al/Cu foil combination is well suited, serving as a low energy bandpass filter below the Cu L-edge at 933 eV. A high resolution grating spectrometer is used to measure the transmission of a candidate filter with an intense laser-produced x-ray backlighter developed at the Lawrence Livermore National Laboratory Jupiter Laser Facility Janus. The methodology and discussion of the observed fine structure above the Cu L-edge will be presented. PMID- 21034029 TI - Quasimonochromatic x-ray backlighting on the COrnell Beam Research Accelerator (COBRA) pulsed power generator. AB - Monochromatic x-ray backlighting has been employed with great success for imaging of plasmas with strong self-emission such as x-pinches and wire array z-pinches. However, implementation of a monochromatic backlighting system typically requires extremely high quality spherically bent crystals which are difficult to manufacture and can be prohibitively expensive. Furthermore, the crystal must have a direct line of sight to the object, which typically emits copious amounts of radiation and debris. We present a quasimonochromatic x-ray backlighting system which employs an elliptically bent mica crystal as the dispersive element. In this scheme a narrow band of continuum radiation is selected for imaging, instead of line radiation in the case of monochromatic imaging. The flat piece of mica is bent using a simple four-point bending apparatus that allows the curvature of the crystal to be adjusted in situ for imaging in the desired wavelength band. This system has the advantage that it is very cost effective, has a large aperture, and is extremely flexible. The principles of operation of the system are discussed and its performance is analyzed. PMID- 21034030 TI - Prototype high resolution multienergy soft x-ray array for NSTX. AB - A novel diagnostic design seeks to enhance the capability of multienergy soft x ray (SXR) detection by using an image intensifier to amplify the signals from a larger set of filtered x-ray profiles. The increased number of profiles and simplified detection system provides a compact diagnostic device for measuring T(e) in addition to contributions from density and impurities. A single-energy prototype system has been implemented on NSTX, comprised of a filtered x-ray pinhole camera, which converts the x-rays to visible light using a CsI:Tl phosphor. SXR profiles have been measured in high performance plasmas at frame rates of up to 10 kHz, and comparisons to the toroidally displaced tangential multi-energy SXR have been made. PMID- 21034031 TI - Charge-injection-device performance in the high-energy-neutron environment of laser-fusion experiments. AB - Charge-injection devices (CIDs) are being used to image x rays in laser-fusion experiments on the University of Rochester's OMEGA Laser System. The CID cameras are routinely used up to the maximum neutron yields generated (~10(14) DT). The detectors are deployed in x-ray pinhole cameras and Kirkpatrick-Baez microscopes. The neutron fluences ranged from ~10(7) to ~10(9) neutrons/cm(2) and useful x-ray images were obtained even at the highest fluences. It is intended to use CID cameras at the National Ignition Facility (NIF) as a supporting means of recording x-ray images. The results of this work predict that x-ray images should be obtainable on the NIF at yields up to ~10(15), depending on distance and shielding. PMID- 21034032 TI - Development of optics for x-ray phase-contrast imaging of high energy density plasmas. AB - Phase-contrast or refraction-enhanced x-ray radiography can be useful for the diagnostic of low-Z high energy density plasmas, such as imploding inertial confinement fusion (ICF) pellets, due to its sensitivity to density gradients. To separate and quantify the absorption and refraction contributions to x-ray images, methods based on microperiodic optics, such as shearing interferometry, can be used. To enable applying such methods with the energetic x rays needed for ICF radiography, we investigate a new type of optics consisting of grazing incidence microperiodic mirrors. Using such mirrors, efficient phase-contrast imaging systems could be built for energies up to ~100 keV. In addition, a simple lithographic method is proposed for the production of the microperiodic x-ray mirrors based on the difference in the total reflection between a low-Z substrate and a high-Z film. Prototype mirrors fabricated with this method show promising characteristics in laboratory tests. PMID- 21034033 TI - Uncertainty analysis technique for OMEGA Dante measurements. AB - The Dante is an 18 channel x-ray filtered diode array which records the spectrally and temporally resolved radiation flux from various targets (e.g., hohlraums, etc.) at x-ray energies between 50 eV and 10 keV. It is a main diagnostic installed on the OMEGA laser facility at the Laboratory for Laser Energetics, University of Rochester. The absolute flux is determined from the photometric calibration of the x-ray diodes, filters and mirrors, and an unfold algorithm. Understanding the errors on this absolute measurement is critical for understanding hohlraum energetic physics. We present a new method for quantifying the uncertainties on the determined flux using a Monte Carlo parameter variation technique. This technique combines the uncertainties in both the unfold algorithm and the error from the absolute calibration of each channel into a one sigma Gaussian error function. One thousand test voltage sets are created using these error functions and processed by the unfold algorithm to produce individual spectra and fluxes. Statistical methods are applied to the resultant set of fluxes to estimate error bars on the measurements. PMID- 21034034 TI - The first experimental results from x-ray imaging crystal spectrometer for KSTAR. AB - The x-ray imaging crystal spectrometer (XICS) for the Korea Superconducting Tokamak Advanced Research has been first applied for the experimental campaign in 2009. The XICS was designed to provide measurements of the profiles of the ion and electron temperatures from the heliumlike argon (Ar XVII) spectra. The basic functions of the XICS are properly working although some satellites lines are not well matched with the expected theoretical values. The initial experimental results from the XICS are briefly described. PMID- 21034035 TI - Transmission grating based extreme ultraviolet imaging spectrometer for time and space resolved impurity measurements. AB - A free standing transmission grating based imaging spectrometer in the extreme ultraviolet range has been developed for the National Spherical Torus Experiment (NSTX). The spectrometer operates in a survey mode covering the approximate spectral range from 30 to 700 A and has a resolving capability of deltalambda/lambda on the order of 3%. Initial results from space resolved impurity measurements from NSTX are described in this paper. PMID- 21034036 TI - Development of two-channel prototype ITER vacuum ultraviolet spectrometer with back-illuminated charge-coupled device and microchannel plate detectors. AB - A vacuum ultraviolet (VUV) spectrometer of a five-channel spectral system is designed for ITER main plasma impurity measurement. To develop and verify the system design, a two-channel prototype system is fabricated with No. 3 (14.4-31.8 nm) and No. 4 (29.0-60.0 nm) among the five channels. The optical system consists of a collimating mirror to collect the light from source to slit, two holographic diffraction gratings with toroidal geometry, and two different electronic detectors. For the test of the prototype system, a hollow cathode lamp is used as a light source. To find the appropriate detector for ITER VUV system, two kinds of detectors of the back-illuminated charge-coupled device and the microchannel plate electron multiplier are tested, and their performance has been investigated. PMID- 21034038 TI - Measurement of the ratio of hydrogen to deuterium at the KSTAR 2009 experimental campaign. AB - The control of the ratio of hydrogen to the deuterium is one of the very important issues for ion cyclotron range of frequency (ICRF) minority heating as well as the plasma wall interaction in the tokamak. The ratio of hydrogen to deuterium during the tokamak shot was deduced from the emission spectroscopy measurements during the KSTAR 2009 experimental campaign. Graphite tiles were used for the plasma facing components (PFCs) at KSTAR and its surface area exposed to the plasma was about 11 m(2). The data showed that it remained as high as around 50% during the campaign period because graphite tiles were exposed to the air for about two months and the hydrogen contents at the tiles are not fully pumped out due to the lack of baking on the PFC in the 2009 campaign. The validation of the spectroscopy method was checked by using the Zeeman effects and the ratio of hydrogen to the deuterium is compared with results from the residual gas analysis. During the tokamak shot, the ratio is low below 10% initially and saturated after around 1 s. When there is a hydrogen injection to the vessel via ion cyclotron wall conditioning and the boronization process where the carbone is used, the ratio of the hydrogen to the deuterium is increased by up to 100% and it recovers to around 50% after one day of operation. However it does not decrease below 50% at the end of the experimental campaign. It was found that the full baking on the PFC (with a high temperature and sufficient vacuum pumping) is required for the ratio control which guarantees the efficient ICRF heating at the KSTAR 2010 experimental campaign. PMID- 21034037 TI - Development of an x-ray imaging system for the Laser Megajoule (LMJ). AB - This imaging system aims at recording images of the core size and shape of an imploding deuterium-tritium (DT) microballoon on LMJ inertial confinement fusion (ICF) experiments. Image acquisition is difficult due to the harsh surrounding created by the fusion reaction, which affects system specifications. This one is made of a scintillator, an optical relay, and a CCD camera shielded from the surrounding. The system was tested on different facilities at CEA/DIF, where a spatial resolution of 120 MUm was achieved and gamma dose up to 20 rad effects were measured. Setup and performed test are described. PMID- 21034039 TI - Application of optical emission spectroscopy for He I considering the spatial structure of radiation trapping in MAP-II divertor simulator. AB - The He I optical emission spectroscopy that considers the spatial structure of radiation trapping was proposed by us and was applied to a MAP-II divertor simulator. The spatial distribution of the optical escape factor was calculated from the n (1)P (n>=3) state profiles measured by visible spectroscopy. The profile of 2 (1)P, which is immeasurable by visible spectroscopy, needs to be broader than that of the 3 (1)P state. The sensitivity of the 2 (1)P profile to the T(e) value estimated by He I spectroscopy is investigated. PMID- 21034040 TI - Dynamics of vapor emissions at wire explosion threshold. AB - X-pinch plasmas have been actively studied in the recent years. Numerical simulation of the ramp-up of metallic vapor emissions from wire specimens shows that under impulsive Ohmic heating the wire core invariably reaches a supercritical state before explosion. The heating rate depends sensitively on the local wire resistance, leading to highly variable vapor emission flux along the wire. To examine the vapor emission process, we have visualized nickel wire explosions by means of shock formation in air. In a single explosion as captured by shadowgraphy, there usually appear several shocks with spherical or cylindrical wave front originating from different parts of the wire. Growth of various shock fronts in time is well characterized by a power-law scaling in one form or another. Continuum emission spectra are obtained and calibrated to measure temperature near the explosion threshold. Shock front structures and vapor plume temperature are examined. PMID- 21034041 TI - Divertor IR thermography on Alcator C-Mod. AB - Alcator C-Mod is a particularly challenging environment for thermography. It presents issues that will similarly face ITER, including low-emissivity metal targets, low-Z surface films, and closed divertor geometry. In order to make measurements of the incident divertor heat flux using IR thermography, the C-Mod divertor has been modified and instrumented. A 6 degrees toroidal sector has been given a 2 degrees toroidal ramp in order to eliminate magnetic field-line shadowing by imperfectly aligned divertor tiles. This sector is viewed from above by a toroidally displaced IR camera and is instrumented with thermocouples and calorimeters. The camera provides time histories of surface temperatures that are used to compute incident heat-flux profiles. The camera sensitivity is calibrated in situ using the embedded thermocouples, thus correcting for changes and nonuniformities in surface emissivity due to surface coatings. PMID- 21034042 TI - Modeling of neutron induced backgrounds in x-ray framing cameras. AB - Fast neutrons from inertial confinement fusion implosions pose a severe background to conventional multichannel plate (MCP)-based x-ray framing cameras for deuterium-tritium yields >10(13). Nuclear reactions of neutrons in photosensitive elements (charge coupled device or film) cause some of the image noise. In addition, inelastic neutron collisions in the detector and nearby components create a large gamma pulse. The background from the resulting secondary charged particles is twofold: (1) production of light through the Cherenkov effect in optical components and by excitation of the MCP phosphor and (2) direct excitation of the photosensitive elements. We give theoretical estimates of the various contributions to the overall noise and present mitigation strategies for operating in high yield environments. PMID- 21034043 TI - Experimental study of neutron induced background noise on gated x-ray framing cameras. AB - A temporally gated x-ray framing camera based on a proximity focus microchannel plate is one of the most important diagnostic tools of inertial confinement fusion experiments. However, fusion neutrons produced in imploded capsules interact with structures surrounding the camera and produce background to x-ray signals. To understand the mechanisms of this neutron induced background, we tested several gated x-ray cameras in the presence of 14 MeV neutrons produced at the Omega laser facility. Differences between background levels observed with photographic film readout and charge-coupled-device readout have been studied. PMID- 21034044 TI - A new double-foil soft x-ray array to measure T(e) on the MST reversed field pinch. AB - A soft x-ray (SXR) diagnostic to measure electron temperature on the Madison Symmetric Torus using two complementary methods is presented. Both methods are based on the double-foil technique, which calculates electron temperature via the ratio of SXR bremsstrahlung emission from the plasma in two different energy ranges. The tomographic emissivity method applies the double-foil technique to a tomographic reconstruction of SXR emissivity, creating a two-dimensional map of temperature throughout the plasma. In contrast, the direct brightness method applies the double-foil technique directly to the measured brightness and generates vertical and horizontal radial profiles. Extensive modeling demonstrates advantages and limitations in both techniques. For example, although the emissivity technique provides a two-dimensional mapping of temperature, its reliance on multiple tomographic inversions introduces some artifacts into the results. On the other hand, the more direct brightness technique avoids these artifacts but is only able to provide a radial profile of electron temperature. PMID- 21034045 TI - Heuristic optimization in penumbral image for high resolution reconstructed image. AB - Penumbral imaging is a technique which uses the fact that spatial information can be recovered from the shadow or penumbra that an unknown source casts through a simple large circular aperture. The size of the penumbral image on the detector can be mathematically determined as its aperture size, object size, and magnification. Conventional reconstruction methods are very sensitive to noise. On the other hand, the heuristic reconstruction method is very tolerant of noise. However, the aperture size influences the accuracy and resolution of the reconstructed image. In this article, we propose the optimization of the aperture size for the neutron penumbral imaging. PMID- 21034046 TI - Design of dynamic Hohlraum opacity samples to increase measured sample density on Z. AB - We are attempting to measure the transmission of iron on Z at plasma temperatures and densities relevant to the solar radiation and convection zone boundary. The opacity data published by us to date has been taken at an electron density about a factor of 10 below the 9*10(22)/cm(3) electron density of this boundary. We present results of two-dimensional (2D) simulations of the heating and expansion of an opacity sample driven by the dynamic Hohlraum radiation source on Z. The aim of the simulations is to design foil samples that provide opacity data at increased density. The inputs or source terms for the simulations are spatially and temporally varying radiation temperatures with a Lambertian angular distribution. These temperature profiles were inferred on Z with on-axis time resolved pinhole cameras, x-ray diodes, and bolometers. A typical sample is 0.3 MUm of magnesium and 0.078 MUm of iron sandwiched between 10 MUm layers of plastic. The 2D LASNEX simulations indicate that to increase the density of the sample one should increase the thickness of the plastic backing. PMID- 21034047 TI - Characterizing high energy spectra of NIF ignition Hohlraums using a differentially filtered high energy multipinhole x-ray imager. AB - Understanding hot electron distributions generated inside Hohlraums is important to the national ignition campaign for controlling implosion symmetry and sources of preheat. While direct imaging of hot electrons is difficult, their spatial distribution and spectrum can be deduced by detecting high energy x-rays generated as they interact with target materials. We used an array of 18 pinholes with four independent filter combinations to image entire Hohlraums with a magnification of 0.87* during the Hohlraum energetics campaign on NIF. Comparing our results with Hohlraum simulations indicates that the characteristic 10-40 keV hot electrons are mainly generated from backscattered laser-plasma interactions rather than from Hohlraum hydrodynamics. PMID- 21034048 TI - Phase-contrast imaging using ultrafast x-rays in laser-shocked materials. AB - High-energy x-rays, >10 keV, can be efficiently produced from ultrafast laser target interactions with many applications to dense target materials in inertial confinement fusion and high-energy density physics. These same x-rays can also be applied to measurements of low-density materials inside high-density Hohlraum environments. In the experiments presented, high-energy x-ray images of laser shocked polystyrene are produced through phase contrast imaging. The plastic targets are nominally transparent to traditional x-ray absorption but show detailed features in regions of high density gradients due to refractive effects often called phase contrast imaging. The 200 TW Trident laser is used both to produce the x-ray source and to shock the polystyrene target. X-rays at 17 keV produced from 2 ps, 100 J laser interactions with a 12 MUm molybdenum wire are used to produce a small source size, required for optimizing refractive effects. Shocks are driven in the 1 mm thick polystyrene target using 2 ns, 250 J, 532 nm laser drive with phase plates. X-ray images of shocks compare well to one dimensional hydro calculations. PMID- 21034049 TI - Density measurements using coherence imaging spectroscopy based on Stark broadening. AB - A coherence imaging camera has been set up at Pilot-PSI. The system is to be used for imaging the plasma density through the Stark effect broadening of the H(gamma) line. Local density values are then obtained by the Abel inversion of the measured interferometric fringe contrast. This report will present the instrument setup and proof-of-principle demonstration. The inverted spatial electron density profiles obtained near the cascaded arc source of Pilot-PSI in discharges with axial magnetic field of B=0.4 T are compared with an independent measurement of electron density by Thomson scattering and good agreement is found. PMID- 21034050 TI - Bragg diffraction using a 100 ps 17.5 keV x-ray backlighter and the Bragg diffraction imager. AB - A new diagnostic for measuring Bragg diffraction of petawatt-generated high energy x rays off a laser-compressed crystal was designed and tested successfully at the Omega EP laser facility on static Mo and Ta (111) oriented single crystal samples using a 17.5 keV Mo Kalpha backlighter. The Bragg diffraction imager consists of a heavily shielded enclosure and a precisely positioned beam block attached to the enclosure by an aluminum arm. Fuji image plates are used as the x ray detectors. The diffraction from Mo and Ta (222) crystal planes was clearly detected with a high signal-to-noise. This technique will be applied to shock- and quasi-isentropically loaded single crystals on the Omega EP laser. PMID- 21034051 TI - Characterization of a 2D soft x-ray tomography camera with discrimination in energy bands. AB - A gas detector with a 2D pixel readout is proposed for a future soft x-ray (SXR) tomography with discrimination in energy bands separately per pixel. The detector has three gas electron multiplier foils for the electron amplification and it offers the advantage, compared with the single stage, to be less sensitive to neutrons and gammas. The energy resolution and the detection efficiency of the detector have been accurately studied in the laboratory with continuous SXR spectra produced by an electronic tube and line emissions produced by fluorescence (K, Fe, and Mo) in the range of 3-17 keV. The front-end electronics, working in photon counting mode with a selectable threshold for pulse discrimination, is optimized for high rates. The distribution of the pulse amplitude has been indirectly derived by means of scans of the threshold. Scans in detector gain have also been performed to assess the capability of selecting different energy ranges. PMID- 21034052 TI - Development of a realistic photonic modeling for the evaluation of infrared reflections in the metallic environment of ITER. AB - In nuclear fusion experiments, the plasma facing components are exposed to high heat fluxes and infrared (IR) imaging diagnostics are routinely used for surveying their surface temperature for preventing damages. However the future use of metallic components in the ITER tokamak adds complications in temperature estimation. Indeed, low and variable emissivity of the observed surface and the multiple reflections of the light coming from hot regions will have to be understood and then taken into account. In this paper, a realistic photonic modeling based on Monte Carlo ray-tracing codes is used to predict the global response of the complete IR survey system. This also includes the complex vessel geometry and the thermal and optical surface properties using the bidirectional reflectivity distribution function that models the photon-material interactions. The first results of this simulation applied to a reference torus are presented and are used as a benchmark to investigate the validity of the global model. Finally the most critical key model parameters in the reflected signals are identified and their contribution is discussed. PMID- 21034053 TI - Development of a compact tomography camera system using a multianode photomultiplier tube for compact torus experiments. AB - A compact tomography camera system consisting of a photomultiplier tube, a multislit optical system, and a band-pass interference filter has been developed. The viewing area and spatial resolution can be configured by the arrangement of the slit system. The camera system has been specially designed for self-organized compact torus experiments having strong magnetohydrodynamics events with a submicrosecond time-scale. The developed system has been tested on a field reversed configuration formed by the field-reversed theta-pinch. Performance evaluation of the system has been performed by comparison to the former optical system. PMID- 21034054 TI - Mapping the ionization state of laser-irradiated Ar gas jets with multiwavelength monochromatic x-ray imaging. AB - Two-dimensional monochromatic images of fast-electron stimulated Ar Kalpha and He alpha x-ray self-emission have recorded a time-integrated map of the extent of Ar(~6+) and Ar(16+) ions, respectively, within a high density (10(20) cm(-3) atomic density) Ar plasma. This plasma was produced by irradiating a 2 mm wide clustering Ar gas jet with an ultrahigh intensity (10(19) W/cm(2), 50 TW) Ti:sapphire laser operating at 800 nm. Spherically bent quartz crystals in the 200 (for Kalpha) and 201 (for He-alpha) planes were used as near-normal incidence reflective x-ray optics. We see that a large (830 MUm long) region of plasma emits Kalpha primarily along the laser axis, while the He-alpha emission is confined to smaller hot spot (230 MUm long) region that likely corresponds to the focal volume of the f/8 laser beam. X-ray spectra from a Bragg spectrometer operating in the von Hamos geometry indicate that the centroids of the Kalpha and He-alpha emission regions are separated by approximately 330 MUm along the laser axis. PMID- 21034055 TI - High speed digital holography for density and fluctuation measurements (invited). AB - The state of the art in electro-optics has advanced to the point where digital holographic acquisition of wavefronts is now possible. Holographic wavefront acquisition provides the phase of the wavefront at every measurement point. This can be done with accuracy on the order of a thousandth of a wavelength, given that there is sufficient care in the design of the system. At wave frequencies which are much greater than the plasma frequency, the plasma index of refraction is linearly proportional to the electron density and wavelength, and the measurement of the phase of a wavefront passing through the plasma gives the chord-integrated density directly for all points measured on the wavefront. High speed infrared cameras (up to ~40,000 fps at ~64*4 pixels) with resolutions up to 640*512 pixels suitable for use with a CO(2) laser are readily available, if expensive. PMID- 21034056 TI - Doppler coherence imaging and tomography of flows in tokamak plasmas (invited). AB - This article describes the results of spatial heterodyne Doppler "coherence imaging" of carbon ion flows in the divertor region of the DIII-D tokamak. Spatially encoded interferometric projections of doubly ionized carbon emission at 465 nm have been demodulated and tomographically inverted to obtain the spatial distribution of the carbon ion parallel flow and emissivity. The operating principles of the new instruments are described, and the link between measured properties and line integrals of the flow field are established. An iterative simultaneous arithmetic reconstruction procedure is applied to invert the interferometric phase shift projections, and the reconstructed parallel flow field amplitudes are found to be in reasonable agreement with UEDGE modeling. PMID- 21034057 TI - Monochromatic x-ray radiography for areal-density measurement of inertial fusion energy fuel in fast ignition experiment. AB - Ultrafast, two-dimensional x-ray imaging is an important diagnostics for the inertial fusion energy research, especially in investigating implosion dynamics at the final stage of the fuel compression. Although x-ray radiography was applied to observing the implosion dynamics, intense x-rays emitted from the high temperature and dense fuel core itself are often superimposed on the radiograph. This problem can be solved by coupling the x-ray radiography with monochromatic x ray imaging technique. In the experiment, 2.8 or 5.2 keV backlight x-rays emitted from laser-irradiated polyvinyl chloride or vanadium foils were selectively imaged by spherically bent quartz crystals with discriminating the out-of-band emission from the fuel core. This x-ray radiography system achieved 24 MUm and 100 ps of spatial and temporal resolutions, respectively. PMID- 21034058 TI - Standard design for National Ignition Facility x-ray streak and framing cameras. AB - The x-ray streak camera and x-ray framing camera for the National Ignition Facility were redesigned to improve electromagnetic pulse hardening, protect high voltage circuits from pressure transients, and maximize the use of common parts and operational software. Both instruments use the same PC104 based controller, interface, power supply, charge coupled device camera, protective hermetically sealed housing, and mechanical interfaces. Communication is over fiber optics with identical facility hardware for both instruments. Each has three triggers that can be either fiber optic or coax. High voltage protection consists of a vacuum sensor to enable the high voltage and pulsed microchannel plate phosphor voltage. In the streak camera, the high voltage is removed after the sweep. Both rely on the hardened aluminum box and a custom power supply to reduce electromagnetic pulse/electromagnetic interference (EMP/EMI) getting into the electronics. In addition, the streak camera has an EMP/EMI shield enclosing the front of the streak tube. PMID- 21034059 TI - Time-resolved spectra of dense plasma focus using spectrometer, streak camera, and CCD combination. AB - A time-resolving spectrographic instrument has been assembled with the primary components of a spectrometer, image-converting streak camera, and CCD recording camera, for the primary purpose of diagnosing highly dynamic plasmas. A collection lens defines the sampled region and couples light from the plasma into a step index, multimode fiber which leads to the spectrometer. The output spectrum is focused onto the photocathode of the streak camera, the output of which is proximity-coupled to the CCD. The spectrometer configuration is essentially Czerny-Turner, but off-the-shelf Nikon refraction lenses, rather than mirrors, are used for practicality and flexibility. Only recently assembled, the instrument requires significant refinement, but has now taken data on both bridge wire and dense plasma focus experiments. PMID- 21034060 TI - Simulation of a tangential soft x-ray imaging system. AB - Tangentially viewing soft x-ray (SXR) cameras are capable of detecting nonaxisymmetric plasma structures in magnetically confined plasmas. They are particularly useful for studying stationary perturbations or phenomenon that occur on a timescale faster than the plasma rotation period. Tangential SXR camera diagnostics are planned for the DIII-D and NSTX tokamaks to elucidate the static edge magnetic structure during the application of 3D perturbations. To support the design of the proposed diagnostics, a synthetic diagnostic model was developed using the CHIANTI database to estimate the SXR emission. The model is shown to be in good agreement with the measurements from an existing tangential SXR camera diagnostic on NSTX. PMID- 21034061 TI - 2D soft x-ray system on DIII-D for imaging the magnetic topology in the pedestal region. AB - A new tangential two-dimensional soft x-ray imaging system (SXRIS) is being designed to examine the edge island structure in the lower X-point region of DIII D. Plasma shielding and/or amplification of the calculated vacuum islands may play a role in the suppression of edge-localized modes via resonant magnetic perturbations (RMPs). The SXRIS is intended to improve the understanding of three dimensional (3D) phenomena associated with RMPs. This system utilizes a tangential view with a pinhole imaging system and spectral filtering with beryllium foils. SXR emission is chosen to avoid line radiation and allows suitable signal at the top of a H-mode pedestal where T(e)~1-2 keV. A synthetic diagnostic calculation based on 3D SXR emissivity estimates is used to help assess signal levels and resolution of the design. A signal-to-noise ratio of 10 at 1 cm resolution is expected for the perturbed signals, which are sufficient to resolve most of the predicted vacuum island sizes. PMID- 21034062 TI - Development of multi-channel electron spectrometer. AB - In order to obtain the angular dependent electron energy distributions, we developed a multichannel electron spectrometer (MCESM) with high energy and angular resolutions. The MCESM consists of seven small electron spectrometers set in every 5 degrees on the basement, each of which detection range is up to 25 MeV. In the experiment, we successfully obtained electron spectra from imploded cone-shell target as well as gold plane target irradiated by ultraintense (300 J/5 ps) laser beam. PMID- 21034063 TI - Development of a short duration backlit pinhole for radiography on the National Ignition Facility. AB - Experiments on the National Ignition Facility (NIF) will require bright, short duration, near-monochromatic x-ray backlighters for radiographic diagnosis of many high-energy density systems. This paper details a vanadium pinhole backlighter producing (1.8+/-0.5)*10(15) x-ray photons into 4pi sr near the vanadium He-like characteristic x-ray energy of 5.18 keV. The x-ray yield was quantified from a set of Ross filters imaged to a calibrated image plate, with the Dante diagnostic used to confirm the quasimonochromatic nature of the spectrum produced. Additionally, an x-ray film image shows a source-limited image resolution of 26 MUm from a 20 MUm diameter pinhole. PMID- 21034064 TI - Optimizing the operation of a high resolution vertical Johann spectrometer using a high energy fluorescer x-ray source. AB - This paper describes the operation and testing for a vertical Johann spectrometer (VJS) operating in the 13 keV range. The spectrometer is designed to use thin curved mica crystals or thick germanium crystals. The VJS must have a resolution of E/DeltaE=3000 or better to measure the Doppler broadening of highly ionized krypton and operate at a small x-ray angle in order to be used as a diagnostic in a laser plasma target chamber. The VJS was aligned, tested, and optimized using a fluorescer type high energy x-ray (HEX) source located at National Security Technologies (NSTec), LLC, in Livermore, CA. The HEX uses a 160 kV x-ray tube to excite fluorescence from various targets. Both rubidium and bismuth fluorescers were used for this effort. This presentation describes the NSTec HEX system and the methods used to optimize and characterize the VJS performance. PMID- 21034065 TI - Images of the laser entrance hole from the static x-ray imager at NIF. AB - The static x-ray imager at the National Ignition Facility is a pinhole camera using a CCD detector to obtain images of Hohlraum wall x-ray drive illumination patterns seen through the laser entrance hole (LEH). Carefully chosen filters, combined with the CCD response, allow recording images in the x-ray range of 3-5 keV with 60 MUm spatial resolution. The routines used to obtain the apparent size of the backlit LEH and the location and intensity of beam spots are discussed and compared to predictions. A new soft x-ray channel centered at 870 eV (near the x ray peak of a 300 eV temperature ignition Hohlraum) is discussed. PMID- 21034066 TI - A hardened gated x-ray imaging diagnostic for inertial confinement fusion experiments at the National Ignition Facility. AB - A gated x-ray detector is under development for use at the National Ignition Facility that is intended to provide plasma emission images in the presence of neutron yields up to 10(15) expected during inertial confinement fusion experiments with layered cryogenic targets. These images are expected to provide valuable time-resolved measurements of core and fuel symmetries. Additional capabilities of this instrument will include the ability to make spatially resolved electron temperature measurements. A description of this instrument and its operation is given with emphasis on features that differentiate it from previous designs. PMID- 21034067 TI - Radiation hardening of gated x-ray imagers for the National Ignition Facility (invited). AB - The National Ignition Facility will soon be producing x-ray flux and neutron yields higher than any produced in laser driven implosion experiments in the past. Even a non-igniting capsule will require x-ray imaging of near burning plasmas at 10(17) neutrons, requiring x-ray recording systems to work in more hostile conditions than we have encountered in past laser facilities. We will present modeling, experimental data and design concepts for x-ray imaging with electronic recording systems for this environment (ARIANE). A novel instrument, active readout in a nuclear environment, is described which uses the time-of flight difference between the gated x-ray signal and the neutron which induces a background signal to increase the yield at which gated cameras can be used. PMID- 21034069 TI - High-performance time-resolved fluorescence by direct waveform recording. AB - We describe a high-performance time-resolved fluorescence (HPTRF) spectrometer that dramatically increases the rate at which precise and accurate subnanosecond resolved fluorescence emission waveforms can be acquired in response to pulsed excitation. The key features of this instrument are an intense (1 MUJ/pulse), high-repetition rate (10 kHz), and short (1 ns full width at half maximum) laser excitation source and a transient digitizer (0.125 ns per time point) that records a complete and accurate fluorescence decay curve for every laser pulse. For a typical fluorescent sample containing a few nanomoles of dye, a waveform with a signal/noise of about 100 can be acquired in response to a single laser pulse every 0.1 ms, at least 10(5) times faster than the conventional method of time-correlated single photon counting, with equal accuracy and precision in lifetime determination for lifetimes as short as 100 ps. Using standard single lifetime samples, the detected signals are extremely reproducible, with waveform precision and linearity to within 1% error for single-pulse experiments. Waveforms acquired in 0.1 s (1000 pulses) with the HPTRF instrument were of sufficient precision to analyze two samples having different lifetimes, resolving minor components with high accuracy with respect to both lifetime and mole fraction. The instrument makes possible a new class of high-throughput time resolved fluorescence experiments that should be especially powerful for biological applications, including transient kinetics, multidimensional fluorescence, and microplate formats. PMID- 21034070 TI - The Fourier transform spectrometer of the Universite Pierre et Marie Curie QualAir platform. AB - A Bruker Optics IFS 125HR Fourier transform spectrometer (FTS) and the Laboratoire de Physique Moleculaire pour l'Atmosphere et l'Astrophysique retrieval algorithm were adapted for ground based atmospheric measurements. As one of the major instruments of the experimental research platform QualAir, this FTS is dedicated to study the urban air composition of large megacity such as Paris. The precise concentration measurements of the most important atmospheric pollutants are a key to improve the understanding and modeling of urban air pollution processes. Located in the center of Paris, this remote sensing spectrometer enables to monitor many pollutants. Examples for NO(2) and CO are demonstrating the performances of this new experimental setup. PMID- 21034071 TI - Trace gas detection based on off-beam quartz enhanced photoacoustic spectroscopy: optimization and performance evaluation. AB - A gas sensor based on off-beam quartz enhanced photoacoustic spectroscopy was developed and optimized. Specifically, the length and diameter of the microresonator tube were optimized, and the outer tube shape is modified for enhancing the trace gas detection sensitivity. The impact of the distance between the quartz tuning fork and an acoustic microresonator on the sensor performance was experimentally investigated. The sensor performance was evaluated by determining the detection sensitivity to H(2)O vapor in ambient air at normal atmospheric pressure. A normalized noise equivalent absorption coefficient (1sigma) of 6.2*10(-9) cm(-1) W/Hz(1/2) was achieved. PMID- 21034072 TI - Nondestructive measurement of refractive index profile of gradient refractive index rod lens. AB - In this paper, a simple nondestructive method is described to obtain the refractive index profile of a gradient refractive index rod lens by means of optical coherence tomography. The approach exploits the fact that optical coherence tomography provides a direct measurement of the optical path of the light traveled through a gradient refractive index rod lens. The refractive index profile for a gradient refractive index rod lens is retrieved by iterative fitting of the optical path calculated by the ray tracing method with that experimentally measured using optical coherence tomography. The measured refractive index profile is in good agreement with theory. PMID- 21034073 TI - 32 bin near-infrared time-multiplexing detector with attojoule single-shot energy resolution. AB - We present two implementations of photon counting time-multiplexing detectors for near-infrared wavelengths, based on Peltier cooled InGaAs/InP avalanche photodiodes. A first implementation is motivated by practical considerations using only commercially available components. It features 16 bins, pulse repetition rates of up to 22 kHz, and a large range of applicable pulse widths of up to 100 ns. A second implementation is based on rapid gating detectors, permitting dead times below 10 ns. This allows one to realize a high dynamic range 32 bin detector, able to process pulse repetition rates of up to 6 MHz for pulse widths of up to 200 ps. Analysis of the detector response at 16.5% detection efficiency reveals a single-shot energy resolution on the attojoule level. PMID- 21034074 TI - Study on the effect of measuring methods on incident photon-to-electron conversion efficiency of dye-sensitized solar cells by home-made setup. AB - An experimental setup is built for the measurement of monochromatic incident photon-to-electron conversion efficiency (IPCE) of solar cells. With this setup, three kinds of IPCE measuring methods as well as the convenient switching between them are achieved. The setup can also measure the response time and waveform of the short-circuit current of solar cell. Using this setup, IPCE results of dye sensitized solar cells (DSCs) are determined and compared under different illumination conditions with each method. It is found that the IPCE values measured by AC method involving the lock-in technique are sincerely influenced by modulation frequency and bias illumination. Measurements of the response time and waveform of short-circuit current have revealed that this effect can be explained by the slow response of DSCs. To get accurate IPCE values by this method, the measurement should be carried out with a low modulation frequency and under bias illumination. The IPCE values measured by DC method under the bias light illumination will be disturbed since the short-circuit current increased with time continuously due to the temperature rise of DSC. Therefore, temperature control of DSC is considered necessary for IPCE measurement especially in DC method with bias light illumination. Additionally, high bias light intensity (>2 sun) is found to decrease the IPCE values due to the ion transport limitation of the electrolyte. PMID- 21034075 TI - Green and ultraviolet pulse generation with a compact, fiber laser, chirped-pulse amplification system for aerosol fluorescence measurements. AB - We use a compact chirped-pulse amplified system to harmonically generate ultrashort pulses for aerosol fluorescence measurements. The seed laser is a compact, all-normal dispersion, mode-locked Yb-doped fiber laser with a 1050 nm center wavelength operating at 41 MHz. Average powers of more than 1.2 W at 525 nm and 350 mW at 262 nm are generated with <500 fs pulse durations. The pulses are time-stretched with high-dispersion fiber, amplified by a high-power, large mode-area fiber amplifier, and recompressed using a chirped volume holographic Bragg grating. The resulting high-peak-power pulses allow for highly efficient harmonic generation. We also demonstrate for the first time to our knowledge, the use of a mode-locked ultraviolet source to excite individual biological particles and other calibration particles in an inlet air flow as they pass through an optical chamber. The repetition rate is ideal for biofluorescence measurements as it allows faster sampling rates as well as the higher peak powers as compared to previously demonstrated Q-switched systems while maintaining a pulse period that is longer than the typical fluorescence lifetimes. Thus, the fluorescence excitation can be considered to be quasicontinuous and requires no external synchronization and triggering. PMID- 21034076 TI - Faraday rotation data analysis with least-squares elliptical fitting. AB - A method of analyzing Faraday rotation data from pulsed magnetic field measurements is described. The method uses direct least-squares elliptical fitting to measured data. The least-squares fit conic parameters are used to rotate, translate, and rescale the measured data. Interpretation of the transformed data provides improved accuracy and time-resolution characteristics compared with many existing methods of analyzing Faraday rotation data. The method is especially useful when linear birefringence is present at the input or output of the sensing medium, or when the relative angle of the polarizers used in analysis is not aligned with precision; under these circumstances the method is shown to return the analytically correct input signal. The method may be pertinent to other applications where analysis of Lissajous figures is required, such as the velocity interferometer system for any reflector (VISAR) diagnostics. The entire algorithm is fully automated and requires no user interaction. An example of algorithm execution is shown, using data from a fiber-based Faraday rotation sensor on a capacitive discharge experiment. PMID- 21034077 TI - Spatially resolvable optical emission spectrometer for analyzing density uniformity of semiconductor process plasma. AB - We proposed a spatially resolved optical emission spectrometer (SROES) for analyzing the uniformity of plasma density for semiconductor processes. To enhance the spatial resolution of the SROES, we constructed a SROES system using a series of lenses, apertures, and pinholes. We calculated the spatial resolution of the SROES for the variation of pinhole size, and our calculated results were in good agreement with the measured spatial variation of the constructed SROES. The performance of the SROES was also verified by detecting the correlation between the distribution of a fluorine radical in inductively coupled plasma etch process and the etch rate of a SiO(2) film on a silicon wafer. PMID- 21034078 TI - Ultrasensitive nanoparticle detection using a portable whispering gallery mode biosensor driven by a periodically poled lithium-niobate frequency doubled distributed feedback laser. AB - We demonstrate a significant reduction in the limit of label-free detection of individual viral-sized nanoparticles in aqueous solution through the use of a frequency doubled telecom laser constructed from a distributed feedback periodically poled lithium-niobate (DFB-PPLN) union. By driving a whispering gallery mode biosensor near a wavelength of 650 nm with this device we have detected real-time adsorption steps for particles 36 nm in radius with a signal to noise ratio of 8. The noise equivalent detection limit is ~20 ag (17 nm radius). This new lower limit is attributed to the ultralow resonance wavelength noise [(Deltalambda(r))(rms)/lambda(r)<10(-9)] associated with the use of the DFB PPLN device. PMID- 21034079 TI - Microsecond time-resolved Fourier transform infrared analytics in a low pressure glow discharge reactor. AB - A low pressure glow discharge reactor has been designed to allow time-resolved infrared spectroscopic investigation of the discharge zone in practical conditions. The benefits of such reactor are demonstrated through the study of the evolution in the infrared spectra of air/CO(2) gas mixture at the microsecond time-scale. It has been shown that the spectra are greatly affected by the electrical discharge in the 2400-2200 cm(-1) region, where the asymmetric stretch mode of CO(2) falls. The CO(2) molecules are excited through a collision with excited N(2) molecules, where the transfer of energy occurs by a resonant effect. The mechanisms involved are reversible and following plasma pulses. PMID- 21034080 TI - A new imaging method for understanding chemical dynamics: efficient slice imaging using an in-vacuum pixel detector. AB - The implementation of the Timepix complementary metal oxide semiconductor pixel detector in velocity map slice imaging is presented. This new detector approach eliminates the need for gating the imaging detector. In time-of-flight mode, the detector returns the impact position and the time-of-flight of charged particles with 12.5 ns resolution and a dynamic range of about 100 MUs. The implementation of the Timepix detector in combination with a microchannel plate additionally allows for high spatial resolution information via center-of-mass centroiding. Here, the detector was applied to study the photodissociation of NO(2) at 452 nm. The energy resolution observed in the experiment was DeltaE/E=0.05 and is limited by the experimental setup rather than by the detector assembly. All together, this new compact detector assembly is well-suited for slice imaging and is a promising tool for imaging studies in atomic and molecular physics research. PMID- 21034081 TI - A double bend achromat lattice for the Pohang Light Source to reduce emittance and increase number of insertion devices. AB - The Pohang Light Source (PLS) storage ring is a synchrotron light source with the emittance of 18.9 nm at 2.5 GeV and has delivered vacuum ultraviolet and soft x rays during the past 15 years. We investigate a lattice design for the 3 GeV ring for an upgrade project that keeps the existing tunnel. We investigate a double bend achromat (DBA) structure that provides the reduction of emittance by a factor of 3 and the increase of the number of straight section by a factor of 2 than the existing PLS lattice. We present several characteristics on the beam dynamics, dynamic aperture, and optics matching in the low-emittance lattice which includes squeezed space between magnets. Present PLS lattice has 12 long straight sections of 6.8 m long and the lattice is modified to provide the additional 12 short straight sections of 3.7 m long by eliminating a bending magnet in the middle of the cell of the present triplet bending achromat lattice. Thus, the new lattice consists of a total of 24 straight sections that consist of 12*6.8 and 12*3.7 m long straight sections, which can provide the spaces for the 4- and 2-m-long insertion devices. We present the design results in detail for a DBA lattice in 281.82 m long circumference. It is shown that the emittance of 6.2 nm in the lattice can be achieved by allowing nonzero dispersions in the straight sections. The lattice provides high brilliance at the photon energy of a few 10 keV that meets the requirements by synchrotron radiation users; however, it may require a strong focusing and become sensitive to machine errors and effects of insertion devices. Thus, we investigated the dynamic aperture in the lattice by a simulation method and achieved an optimal tune under the strength of sextupole magnets of 500 T/m(2) for the low-emittance ring. We also performed the lattice tunings to restore the optics due to the errors in the low-emittance ring. In result, our designed lattice shows a good optimization in terms of emittance, brilliance, and circumference as a light source for a 3 GeV. PMID- 21034082 TI - Scintillating screens sensitivity and resolution studies for low energy, low intensity beam diagnostics. AB - In order to investigate the limits of scintillating screens for beam profile monitoring in the ultra-low energy, ultra-low intensity regime, CsI:Tl, YAG:Ce, and a Tb glass-based scintillating fiber optic plate (SFOP) were tested. The screens response to 200 and 50 keV proton beams with intensities ranging from a few picoampere down to the subfemtoampere region was examined. In the following paper, the sensitivity and resolution studies are presented in detail for CsI:Tl and the SFOP, the two most sensitive screens. In addition, a possible use of scintillators for ultra-low energy antiproton beam monitoring is discussed. PMID- 21034083 TI - Development and application of setup for ac magnetic field in neutron scattering experiments. AB - We report on a new setup developed for neutron scattering experiments in periodically alternating magnetic fields at the sample position. The assembly consisting of rf generator, amplifier, wide band transformer, and resonance circuit. It allows to generate homogeneous ac magnetic fields over a volume of a few cm(3) and variable within a wide range of amplitudes and frequencies. The applicability of the device is exemplified by ac polarized neutron reflectometry (PNR): a new method established to probe remagnetization kinetics in soft ferromagnetic films. Test experiments with iron films demonstrate that the ac field within the accessible range of frequencies and amplitudes produces a dramatic effect on the PNR signal. This shows that the relevant ac field parameters generated by the device match well with the scales involved in the remagnetization processes. Other possible applications of the rf unit are briefly discussed. PMID- 21034084 TI - The development of enabling technologies for producing active interrogation beams. AB - A U.S./Russian collaboration of accelerator scientists was directed to the development of high averaged-current (~1 mA) and high-quality (emittance ~15 pimm mrad; energy spread ~0.1%) 1.75 MeV proton beams to produce active interrogation beams that could be applied to counterterrorism. Several accelerator technologies were investigated. These included an electrostatic tandem accelerator of novel design, a compact cyclotron, and a storage ring with energy compensation and electron cooling. Production targets capable of withstanding the beam power levels were designed, fabricated, and tested. The cyclotron/storage-ring system was theoretically studied and computationally designed, and the electrostatic vacuum tandem accelerator at BINP was demonstrated for its potential in active interrogation of explosives and special nuclear materials. PMID- 21034085 TI - Measurements of the fast electron bremsstrahlung emission during electron cyclotron resonance heating in the HL-2A tokamak. AB - A fast electron bremsstrahlung (FEB) diagnostic technique based on cadmium telluride (CdTe) detector has been developed recently in the HL-2A tokamak for measurements of the temporal evolution of FEB emission in the energy range of 10 200 keV. With a perpendicular viewing into the plasma on the equatorial plane, the hard x-ray spectra with eight different energy channels are measured. The discrimination of the spectra is implemented by an accurate spectrometry. The system also makes use of fast digitization and software signal processing technology. An ambient environment of neutrons, gammas, and magnetic disturbance requires careful shielding. During electron cyclotron resonance heating, the generation of fast electrons and the oscillations of electron fishbone (e fishbone) have been found. Using the FEB measurement system, it has been experimentally identified that the mode strongly correlates with the electron cyclotron resonance heating produced fast electrons with 30-70 keV. PMID- 21034086 TI - High-performance soft x-ray spectromicroscopy beamline at SSRF. AB - The Shanghai Synchrotron Radiation Facility (SSRF) is the first third-generation synchrotron facility in China and operated at an electron energy of 3.5 GeV. One of the seven beamlines in the first construction phase is devoted to soft x-ray spectromicroscopy and is equipped with an elliptically polarized undulator light source, a plane grating monochromator, and a scanning transmission x-ray microscope end station. Initial results reveal the high performance of this beamline, with an energy resolving power estimated to be over 10,000 at the argon L-edge and a spatial resolution better than 30 nm. PMID- 21034087 TI - Avalanche photodiode based detector for beam emission spectroscopy. AB - An avalanche photodiode based (APD) detector for the visible wavelength range was developed for low light level, high frequency beam emission spectroscopy (BES) experiments in fusion plasmas. This solid state detector has higher quantum efficiency than photomultiplier tubes, and unlike normal photodiodes, it has internal gain. This paper describes the developed detector as well as the noise model of the electronic circuit. By understanding the noise sources and the amplification process, the optimal amplifier and APD reverse voltage setting can be determined, where the signal-to-noise ratio is the highest for a given photon flux. The calculations are compared to the absolute calibration results of the implemented circuit. It was found that for a certain photon flux range, relevant for BES measurements (~10(8)-10(10) photons/s), the new detector is superior to both photomultipliers and photodiodes, although it does not require cryogenic cooling of any component. The position of this photon flux window sensitively depends on the parameters of the actual experimental implementation (desired bandwidth, detector size, etc.) Several detector units based on these developments have been built and installed in various tokamaks. Some illustrative results are presented from the 8-channel trial BES system installed at Mega Ampere Spherical Tokamak (MAST) and the 16-channel BES system installed at the Torus Experiment for Technology Oriented Research (TEXTOR). PMID- 21034088 TI - Low energy-consumption plasma electrolytic oxidation based on grid cathode. AB - Plasma electrolytic oxidation (PEO) has attracted widespread attention owing to the simplicity of operation and the excellent properties of the formed coating. However, wider applications of PEO have been limited due to the high power consumption. This work describes the design and performance of a novel technique named shorter distance PEO (SD-PEO), which is intended for lowering the energy consumption. The key feature of the method is the application of grid cathode to eliminate the gaseous envelope effect and to block of the exchange of charge carries during SD-PEO process. Compared to PEO carried out at a normal electrode distance, e.g., 50 mm, both the voltage drop and the joule heat consumed in the electrolyte at a shorter distance, e.g., of 5 mm (SD-PEO) are relatively small. Consequently, the energy consumption rendered by the novel SD-PEO method may decrease by more than 25%. Our results reveal that SD-PEO is a low energy consumption microarc oxidation technique with more potential in industry applications. PMID- 21034089 TI - Ultrashort electron pulses as a four-dimensional diagnosis of plasma dynamics. AB - We report an ultrafast electron imaging system for real-time examination of ultrafast plasma dynamics in four dimensions. It consists of a femtosecond pulsed electron gun and a two-dimensional single electron detector. The device has an unprecedented capability of acquiring a high-quality shadowgraph image with a single ultrashort electron pulse, thus permitting the measurement of irreversible processes using a single-shot scheme. In a prototype experiment of laser-induced plasma of a metal target under moderate pump intensity, we demonstrated its unique capability of acquiring high-quality shadowgraph images on a micron scale with a-few-picosecond time resolution. PMID- 21034090 TI - High-voltage pulsed generator for dynamic fragmentation of rocks. AB - A portable high-voltage (HV) pulsed generator has been designed for rock fragmentation experiments. The generator can be used also for other technological applications. The installation consists of low voltage block, HV block, coaxial transmission line, fragmentation chamber, and control system block. Low voltage block of the generator, consisting of a primary capacitor bank (300 MUF) and a thyristor switch, stores pulse energy and transfers it to the HV block. The primary capacitor bank stores energy of 600 J at the maximum charging voltage of 2 kV. HV block includes HV pulsed step up transformer, HV capacitive storage, and two electrode gas switch. The following technical parameters of the generator were achieved: output voltage up to 300 kV, voltage rise time of ~50 ns, current amplitude of ~6 kA with the 40 Omega active load, and ~20 kA in a rock fragmentation regime (with discharge in a rock-water mixture). Typical operation regime is a burst of 1000 pulses with a frequency of 10 Hz. The operation process can be controlled within a wide range of parameters. The entire installation (generator, transmission line, treatment chamber, and measuring probes) is designed like a continuous Faraday's cage (complete shielding) to exclude external electromagnetic perturbations. PMID- 21034091 TI - A digital method for separation and reconstruction of pile-up events in germanium detectors. AB - The problem of pulse pile-up is very often encountered in precise measurements of gamma-rays using germanium detectors. The standard method of treating the pile-up events is to identify and reject them using an appropriate electronic system. Digital acquisition techniques now allow the recording of waveforms of pile-up events that can be analyzed and the contributing single pulses recovered, rather than simply tolerating the losses associated with pile-up. In this paper, a method for the off-line digital processing of pile-up events from germanium detectors is demonstrated. The method is based on an appropriate fitting of the detector signals, shaped with a suitable digital pulse shaper. It is shown that the method is able to recover the pile-up events with good accuracy even when the constituent signals are in close proximity. The method is very useful for gamma ray spectroscopy in nuclear physics experiments, where the low intensity signals can be lost due to the pile-up in a high-rate environment. PMID- 21034092 TI - Quantitative scanning probe microscope topographies by charge linearization of the vertical actuator. AB - Many forms of scanning probe microscopy require a piezoelectric actuator to vary the probe-sample distance. Examples include constant-force atomic force microscopy and constant-current scanning tunneling microscopy. In such modes, the topography of the sample is reconstructed from the voltage applied to the vertical piezoelectric actuator. However, piezoelectric actuators exhibit significant hysteresis which can produce up to 14% uncertainty in the reproduced topography. In this work, a charge drive is used to linearize the vertical piezoelectric actuator which reduces the error from 14% to 0.65%. PMID- 21034093 TI - Superresolution confocal technology for displacement measurements based on total internal reflection. AB - In order to achieve a higher axial resolution for displacement measurement, a novel method is proposed based on total internal reflection filter and confocal microscope principle. A theoretical analysis of the basic measurement principles is presented. The analysis reveals that the proposed confocal detection scheme is effective in enhancing the resolution of nonlinearity of the reflectance curve greatly. In addition, a simple prototype system has been developed based on the theoretical analysis and a series of experiments have been performed under laboratory conditions to verify the system feasibility, accuracy, and stability. The experimental results demonstrate that the axial resolution in displacement measurements is better than 1 nm in a range of 200 nm which is threefold better than that can be achieved using the plane reflector. PMID- 21034094 TI - Quantitative studies on inner interfaces in conical metal joints using hard x-ray inline phase contrast radiography. AB - Quantitative investigation of micrometer and submicrometer gaps between joining metal surfaces is applied to conical plug-socket connections in dental titanium implants. Microgaps of widths well beyond the resolving power of industrial x-ray systems are imaged by synchrotron phase contrast radiography. Furthermore, by using an analytical model for the relatively simple sample geometry and applying it to numerical forward simulations of the optical Fresnel propagation, we show that quantitative measurements of the microgap width down to 0.1 MUm are possible. Image data recorded at the BAMline (BESSY-II light source, Germany) are presented, with the resolving power of the imaging system being 4 MUm in absorption mode and ~14 MUm in phase contrast mode (z(2)=0.74 m). Thus, phase contrast radiography, combined with numerical forward simulations, is capable of measuring the widths of gaps that are two orders of magnitude thinner than the conventional detection limit. PMID- 21034095 TI - Probe pressure dependence of nanoscale capacitance-voltage characteristic for AlGaN/GaN heterostructures. AB - This paper investigated the effect of atomic force microscopy probe pressure on capacitance-voltage (C-V) and two-dimensional electron gas (2DEG) characteristics. Based on the experimental results, first principles and charge control model calculations were carried out to explore the origin of the changes in C-V and 2DEG characteristics. It is found that the strain of AlGaN induced by the probe pressure was very limited, thus it did not change the C-V characteristic and 2DEG density. The change of threshold voltage and 2DEG density is mainly attributed to the variation of surface barrier height, which is sensitive to the gap between the probe and the sample. Therefore, to map the electronic properties distribution, one should adopt constant force mode to eliminate the effect of probe pressure. PMID- 21034096 TI - Stabilization of sample temperature in a surface-science vacuum chamber to 0.03 K and quartz-crystal microbalance frequency to 0.06 Hz over 0.5 h. AB - Improvements have been made to a high-stability quartz-crystal microbalance for use in a typical surface-science, ultrahigh vacuum chamber, with a frequency stability of one part in 10(8) (0.06 Hz) over 0.5 h. This gives a resolution equivalent to 2% of an atomic monolayer of oxygen over 0.5 h. The quartz-crystal microbalance (QCM) crystal can be rotated to different surface-analysis positions in the chamber. These characteristics open up the combination of surface and bulk adsorption studies on the same sample without transferring the sample to another chamber. To accomplish this, it was necessary to stabilize the sample temperature to +/-0.03 K over several hours. The oscillator performance is illustrated by the uptake of oxygen by a gold-plated QCM crystal. PMID- 21034097 TI - Circularly polarized luminescence microscopy for the imaging of charge and spin diffusion in semiconductors. AB - Room temperature electronic diffusion is studied in 3 MUm thick epitaxial p(+) GaAs lift-off films using a novel circularly polarized photoluminescence microscope. The method is equivalent to using a standard optical microscope and provides a contactless means to measure both the charge (L) and spin (L(s)) diffusion lengths simultaneously. The measured values of L and L(s) are in excellent agreement with the spatially averaged polarization and a sharp reduction in these two quantities (L from 21.3 to 1.2 MUm and L(s) from 1.3 to 0.8 MUm) is found with increasing surface recombination velocity. Outward diffusion results in a factor of 10 increase in the polarization at the excitation spot. The range of materials to which the technique can be applied, as well as a comparison with other existing methods for the measurement of spin diffusion, is discussed. PMID- 21034098 TI - Development of a synchrotron biaxial tensile device for in situ characterization of thin films mechanical response. AB - We have developed on the DIFFABS-SOLEIL beamline a biaxial tensile machine working in the synchrotron environment for in situ diffraction characterization of thin polycrystalline films mechanical response. The machine has been designed to test compliant substrates coated by the studied films under controlled, applied strain field. Technological challenges comprise the sample design including fixation of the substrate ends, the related generation of a uniform strain field in the studied (central) volume, and the operations from the beamline pilot. Preliminary tests on 150 nm thick W films deposited onto polyimide cruciform substrates are presented. The obtained results for applied strains using x-ray diffraction and digital image correlation methods clearly show the full potentialities of this new setup. PMID- 21034099 TI - Method for cooling nanostructures to microkelvin temperatures. AB - We propose a new scheme aimed at cooling nanostructures to microkelvin temperature based on the well established technique of adiabatic nuclear demagnetization: we attach each device measurement lead to an individual nuclear refrigerator, allowing efficient thermal contact to a microkelvin bath. On a prototype consisting of a parallel network of nuclear refrigerators, temperatures of ~1 mK simultaneously on ten measurement leads have been reached upon demagnetization, thus completing the first steps toward ultracold nanostructures. PMID- 21034100 TI - Development of a nuclear magnetic resonance system for in situ analysis of hydrogen storage materials under high pressures and temperatures. AB - A NMR system for in situ analysis of hydrogen storage materials under high pressure and temperature conditions was developed. The system consists of a gas pressure and flow rate controlling unit, a temperature controller, a high temperature NMR probe tunable for both (1)H and other nuclei, and a sample tube holder. Sample temperature can be controlled up to 623 K by heated N(2) gas flow. Sample tube atmosphere can be substituted by either H(2) or Ar and can be pressurized up to 1 MPa under constant flow rate up to 100 ml/min. During the NMR measurement, the pressure can be adjusted easily by just handle a back pressure valve. On the blank NMR measurement, (1)H background noise was confirmed to be very low. (1)H and (11)B NMR spectrum of LiBH(4) were successfully observed at high temperature for the demonstration of the system. The intensity of the (1)H NMR spectra of H(2) gas was also confirmed to be proportional to the applied pressure. PMID- 21034101 TI - A catalytic reactor for the trapping of free radicals from gas phase oxidation reactions. AB - A catalytic reactor for the trapping of free radicals originating from gas phase catalytic reactions is described and discussed. Radical trapping and identification were initially carried out using a known radical generator such as dicumyl peroxide. The trapping of radicals was further demonstrated by investigating genuine radical oxidation processes, e.g., benzaldehyde oxidation over manganese and cobalt salts. The efficiency of the reactor was finally proven by the partial oxidation of cyclohexane over MoO(3), Cr(2)O(3), and WO(3), which allowed the identification of all the radical intermediates responsible for the formation of the products cyclohexanol and cyclohexanone. Assignment of the trapped radicals was carried out using spin trapping technique and X-band electron paramagnetic resonance spectroscopy. PMID- 21034102 TI - Surface pump-probe femtosecond-laser mass spectrometry: time-, mass-, and velocity-resolved detection of surface reaction dynamics. AB - A detailed account of the experimental methodology of surface pump-probe femtosecond-laser mass spectrometry is presented. This recently introduced technique enables the direct time-resolved investigation of surface reaction dynamics by monitoring the mass and the relative velocity of intermediates and products of a photoinduced surface reaction via multiphoton ionization. As a model system, the photodissociation dynamics of methyl iodide adsorbed at submonolayer coverage on magnesia ultrathin films is investigated. The magnesia surface preparation and characterization as well as the pulsed deposition of methyl iodide are described. The femtosecond-laser excitation (pump) and, in particular, the resonant multiphoton ionization surface detection (probe) schemas are discussed in detail. Results of pump-probe time-resolved methyl and iodine atom detection experiments are presented and the potential of this method for velocity-resolved photofragment analysis is evaluated. PMID- 21034103 TI - A study of J-coupling spectroscopy using the Earth's field nuclear magnetic resonance inside a laboratory. AB - In this paper, an instrumentation of the Earth's field nuclear magnetic resonance (EFNMR) inside a laboratory is presented. A lock-in analysis (LIA) technique was proposed to enhance the signal-to-noise ratio (SNR). A SNR of 137.8 was achieved in a single measurement for 9 ml tap water, and the LIA technique significantly enhanced the SNR to 188 after a 10-average in a noisy laboratory environment. The proton-phosphorus coupling in trimethyl phosphate ((CH(3)O)(3)PO) with J-coupling J[H,F]=(10.99+/-0.013) Hz has been demonstrated. The LIA technique improves the SNR, and a 2.6-fold improvement in SNR over that of the frequency-adjusted averaging is achieved. To reduce the noise in EFNMR, it was suggested that the LIA technique and the first order gradient shim be used to achieve a subhertz linewidth. PMID- 21034104 TI - First experimental demonstration of a photonic band gap channel-drop filter at 240 GHz. AB - We have designed, fabricated, and tested a novel photonic band gap (PBG) channel drop filter (CDF) operating at around 240 GHz. A PBG CDF is a device that allows the channeling of selected frequencies from continuous spectra into separate waveguides through select defects in a PBG structure. It is compact and configurable, and thus, it can be employed for millimeter-wave spectrometry with applications in communications, radio astronomy, and radar receivers for remote sensing and nonproliferation. In this paper we present the design, modeling, and fabrication methods used to produce a silicon-based PBG CDF, and demonstrate its ability to filter the frequency of 240 GHz with a linewidth of approximately 1 GHz and transmission of 25 dB above background. PMID- 21034105 TI - Single-shot electron bunch length measurements using a spatial electro-optical autocorrelation interferometer. AB - A spatial, electro-optical autocorrelation (EOA) interferometer using the vertically polarized lobes of coherent transition radiation (CTR) has been developed as a single-shot electron bunch length monitor at an optical beam port downstream the 100 MeV preinjector LINAC of the Swiss Light Source. This EOA monitor combines the advantages of step-scan interferometers (high temporal resolution) [D. Mihalcea et al., Phys. Rev. ST Accel. Beams 9, 082801 (2006) and T. Takahashi and K. Takami, Infrared Phys. Technol. 51, 363 (2008)] and terahertz gating technologies [U. Schmidhammer et al., Appl. Phys. B: Lasers Opt. 94, 95 (2009) and B. Steffen et al., Phys. Rev. ST Accel. Beams 12, 032802 (2009)] (fast response), providing the possibility to tune the accelerator with an online bunch length diagnostics. While a proof of principle of the spatial interferometer was achieved by step-scan measurements with far-infrared detectors, the single-shot capability of the monitor has been demonstrated by electro-optical correlation of the spatial CTR interference pattern with fairly long (500 ps) neodymium-doped yttrium aluminum garnet (Nd:YAG) laser pulses in a ZnTe crystal. In single-shot operation, variations of the bunch length between 1.5 and 4 ps due to different phase settings of the LINAC bunching cavities have been measured with subpicosecond time resolution. PMID- 21034106 TI - Sensitive surface loop-gap microresonators for electron spin resonance. AB - This work presents the design, construction, and experimental testing of unique sensitive surface loop-gap microresonators for electron spin resonance (ESR) measurements. These resonators are made of "U"-shaped gold structures with typical sizes of 50 and 150 MUm that are deposited on a thin (220 MUm) rutile substrate and fed from the rear by a microstrip line. This allows accommodating a large flat sample above the resonator in addition to having variable coupling properties. Such resonators have a very small volume which, compared to previous designs, improves their absolute spin sensitivity by a factor of more than 2 (based on experimental results). They also have a very high microwave field-power conversion ratio of up to 86 gauss/?Hz. This could facilitate the use of very short excitation pulses with relatively low microwave power. Following the presentation and the discussion of the experimental results, ways to further increase sensitivity significantly are outlined. PMID- 21034107 TI - A Tesla-pulse forming line-plasma opening switch pulsed power generator. AB - A pulsed power generator based on a high-voltage Tesla transformer which charges a 3.85 Omega/55 ns water-filled pulse forming line to 300 kV has been developed at Loughborough University as a training tool for pulsed power students. The generator uses all forms of insulation specific to pulsed power technology, liquid (oil and water), gas (SF(6)), and magnetic insulation in vacuum, and a number of fast voltage and current sensors are implemented for diagnostic purposes. A miniature (centimeter-size) plasma opening switch has recently been coupled to the output of the pulse forming line, with the overall system comprising the first phase of a program aimed at the development of a novel repetitive, table-top generator capable of producing 15 GW pulses for high power microwave loads. Technical details of all the generator components and the main experimental results obtained during the program and demonstrations of their performance are presented in the paper, together with a description of the various diagnostic tools involved. In particular, it is shown that the miniature plasma opening switch is capable of reducing the rise time of the input current while significantly increasing the load power. Future plans are outlined in the conclusions. PMID- 21034108 TI - Improvement in the accuracy of estimating the time-of-flight in an ultrasonic ranging system using multiple square-root unscented Kalman filters. AB - The square-root unscented Kalman filter (SRUKF) is applied to identify the shape parameters of an ultrasonic echo envelope. The SRUKF has better stability than the normal unscented Kalman filter (UKF) because the square-root of the error covariance matrix used in the SRUKF guarantees positive semidefiniteness. Considering the effect of the initial state on the convergence speed of filters, the multi-SRUKF is used to estimate the time-of-flight (TOF). Each SRUKF has a different initial state. The result estimated in a limited time with minimum mean square error is finally adopted. Simulation experiments for various couples of shape parameters and signal-to-noise ratios validate the improvement in the TOF accuracy. Real experiments using the echo signals of a SensComp 600 ultrasonic transducer show that the relative means and standard deviations of the TOF error obtained using the multi-SRUKF method are less than 0.2% and 0.15%, respectively. PMID- 21034109 TI - AC measurement of heat capacity and magnetocaloric effect for pulsed magnetic fields. AB - A new calorimeter for measurements of the heat capacity and magnetocaloric effect of small samples in pulsed magnetic fields is discussed for the exploration of thermal and thermodynamic properties at temperatures down to 2 K. We tested the method up to MU(0)H=50 T, but it could be extended to higher fields. For these measurements we used carefully calibrated bare-chip Cernox((r)) and RuO(2) thermometers, and we present a comparison of their performances. The monotonic temperature and magnetic field dependences of the magnetoresistance of RuO(2) allow thermometry with a precision as good as +/-4 mK at T=2 K. To test the performance of our calorimeter, heat capacity and magnetocaloric effect for the spin-dimer compound Sr(3)Cr(2)O(8) and the triangular lattice antiferromagnet RbFe(MoO(4))(2) are presented. PMID- 21034110 TI - Photoacoustic cell for ultrasound contrast agent characterization. AB - Photoacoustics has emerged as a tool for the study of liquid gel suspension behavior and has been recently employed in a number of new biomedical applications. In this paper, a photoacoustic sensor is presented which was designed and realized for analyzing photothermal signals from solutions filled with microbubbles, commonly used as ultrasound contrast agents in echographic imaging techniques. It is a closed cell device, where photothermal volume variation of an aqueous solution produces the periodic deflection of a thin membrane closing the cell at the end of a short pipe. The cell then acts as a Helmholtz resonator, where the displacement of the membrane is measured through a laser probe interferometer, whereas photoacoustic signal is generated by a laser chopped light beam impinging onto the solution through a glass window. Particularly, the microbubble shell has been modeled through an effective surface tension parameter, which has been then evaluated from experimental data through the shift of the resonance frequencies of the photoacoustic sensor. This shift of the resonance frequencies of the photoacoustic sensor caused by microbubble solutions is high enough for making such a cell a reliable tool for testing ultrasound contrast agent, particularly for bubble shell characterization. PMID- 21034111 TI - Primary measurement of total ultrasonic power with improved accuracy in rf voltage measurement. AB - Out of the various existing ultrasonic power measurement techniques, the radiation force balance method using microbalance is most widely used in low power (below 1 W) regime. The major source of uncertainty associated with this technique is the error in ac voltage measurement applied to the transducer for the generation of ultrasonic waves. The sources that deteriorate the ac voltage measurement accuracy include cable length and impedance mismatch. We introduce a new differential peak to peak measurement approach to reduce the ac voltage measurement error. The method holds the average peak amplitude of each polarity. Ultralow offset difference amplifier is used to measure peak to peak voltage. The method is insensitive to the variations in the dc offset of the source. The functionality of this method has been tested and compared with the conventional rf voltage measurement method. The output of this proposed technique is dc, which can be measured with an error of less than 0.1%. PMID- 21034112 TI - A coaxial thermocouple for shock tunnel applications. AB - A chromel-constantan coaxial surface junction thermocouple has been designed, fabricated, calibrated, and tested to measure the temperature-time history on the surface of a body in a hypersonic freestream of Mach 8 in a shock tunnel. The coaxial thermocouple with a diameter of 3.25 mm was flush mounted in the surface of a hemisphere of 25 mm diameter. The hypersonic freestream was of a very low temperature and density, and had a flow time of about a millisecond. Preliminary test results indicate that the thermocouple is quite sensitive to low temperature rarefied freestreams, and also has a response time of a few microseconds (~5 MUs) to meet the requirements of short duration transient measurements. The sensor developed is accurate, robust, reproducible, and is highly inexpensive. PMID- 21034113 TI - Simultaneous measurement of ultrasonic longitudinal wave velocities and thicknesses of a two layered media in the absence of an interface echo. AB - A measurement technique has been developed to extract the phase information of successive echoes for the simultaneous estimation of thicknesses and ultrasonic velocities of individual layers in a two layered media. The proposed method works in the absence of an interface echo and requires the total thickness of the sample to be known. Experiments have been carried out on two layered samples of white cast iron and gray cast iron with layer thickness variation in the range of 2-8 mm for total thickness variation in the range of 12-13 mm. Comparison with micrographs of a few samples confirmed the model predictions. The model is found to be sensitive to the total sample thickness but fairly insensitive to noise in the data. PMID- 21034114 TI - NMR probe for pressure-jump experiments up to 250 bars and 3 ms jump time. AB - We describe the design and performance of a pressure-jump instrument for time resolved NMR experiments. Initial pressure of up to 250 bars can be produced by means of a HPLC pump and distilled water as a pressure-transmitting liquid. Fast pressure release at a time resolution of 3 ms is achieved using a fast acting valve driven by a piezostack close to the sample chamber. The pressure-jump cell is placed together with two valves in an especially designed NMR probe, which can be used in standard spectrometers with wide-bore magnets. All functions of the instrument are personal computer controlled. The equipment is designed for investigations on systems of biological interest, especially lipid-water dispersions. A theoretical consideration implies that probably the limited speed of valve opening determines the lower boundary of the jump time. The performance is illustrated by time-resolved NMR spectra across the phase transition of a phospholipid-water dispersion after a pressure jump from 100 bars to atmospheric pressure. PMID- 21034115 TI - A compact streak camera for 150 fs time resolved measurement of bright pulses in ultrafast electron diffraction. AB - We have developed a compact streak camera suitable for measuring the duration of highly charged subrelativistic femtosecond electron bunches with an energy bandwidth in the order of 0.1%, as frequently used in ultrafast electron diffraction (UED) experiments for the investigation of ultrafast structural dynamics. The device operates in accumulation mode with 50 fs shot-to-shot timing jitter, and at a 30 keV electron energy, the full width at half maximum temporal resolution is 150 fs. Measured durations of pulses from our UED gun agree well with the predictions from the detailed charged particle trajectory simulations. PMID- 21034116 TI - Microcontroller based system for electrical breakdown time delay measurement in gas-filled devices. AB - This paper presents realization of a digital embedded system for measuring electrical breakdown time delay. The proposed system consists of three major parts: dc voltage supply, analog subsystem, and a digital subsystem. Any dc power source with the range from 100 to 1000 V can be used in this application. The analog subsystem should provide fast and accurate voltage switching on the testing device as well as transform the signals that represent the voltage pulse on the device and the device breakdown into the form suitable for detection by a digital subsystem. The insulated gate bipolar transistor IRG4PH40KD driven by TC429 MOSFET driver is used for high voltage switching on the device. The aim of a digital subsystem is to detect the signals from the analog subsystem and to measure the elapsed time between their occurrences. Moreover, the digital subsystem controls various parameters that influence time delay and provides fast data storage for a large number of measured data. For this propose, we used the PIC18F4550 microcontroller with a full-speed compatible universal serial bus (USB) engine. Operation of this system is verified on different commercial and custom made gas devices with different structure and breakdown mechanisms. The electrical breakdown time delay measurements have been carried out as a function of several parameters, which dominantly influence electrical breakdown time delay. The obtained results have been verified using statistical methods, and they show good agreement with the theory. The proposed system shows good repeatability, sensitivity, and stability for measuring the electrical breakdown time delay. PMID- 21034117 TI - Grazing incidence wide angle x-ray scattering at the wiggler beamline BW4 of HASYLAB. AB - We present an upgrade of the available measurement techniques at the wiggler beamline BW4 of the Hamburger Synchrotronstrahlungslabor (HASYLAB) to grazing incidence wide angle x-ray scattering (GIWAXS). GIWAXS refers to an x-ray diffraction method, which, based on the measurement geometry, is perfectly suited for the investigation of the material crystallinity of surfaces and thin films. It is shown that the overall experimental GIWAXS setup employing a movable CCD detector provides the capability of reliable and reproducible diffraction measurements in grazing incidence geometry. Furthermore, the potential usage of an additional detector enables the simultaneous or successive measurement of GIWAXS and grazing incidence small angle x-ray scattering (GISAXS). The new capability is illustrated by the microbeam GIWAXS measurement of a thin film of the conjugated polymer poly(3-octylthiophene) (P3OT). The investigation reveals the semicrystalline nature of the P3OT film by a clear identification of the wide angle scattering reflexes up to the third order in the [100]-direction as well as the first order in the [010]-direction. The corresponding microbeam GISAXS measurement on the present morphology complements the characterization yielding the complete sample information from subnanometer up to micrometer length scales. PMID- 21034118 TI - On the interpretation of Langmuir probe data inside a spacecraft sheath. AB - If a Langmuir probe is located inside the sheath of a negatively charged spacecraft, there is a risk that the probe characteristic is modified compared to that of a free probe in the ambient plasma. We have studied this probe-in spacecraft-sheath problem in the parameter range of a small Langmuir probe (with radius r(LP)?lambda(D)) using a modified version of the orbit motion limited (OML) probe theory. We find that the ambient electron contribution I(e)(U(LP)) to the probe characteristic is suitably analyzed in terms of three regions of applied probe potential U(LP). In region I, where the probe is negatively charged (i.e., U(LP)U(1), there is first a transition region II in applied potential, U(1) 30 dB was higher in the TORP group compared with the PORP group (p = 0.024) after ossicular reconstruction. The total extrusion rate was 5.2% and the total revision rate was 10.5%. PMID- 21034172 TI - Telephone use among cochlear implanted children. AB - CONCLUSION: Telephone use among implanted children is significantly different from that of the normally hearing population of the same age. OBJECTIVE: To characterize the use of telephone in cochlear implanted children and compare it to that of age-matched normal-hearing children. METHODS: The study (n = 26) and control (n = 27) groups each consisted of children aged 5-17 years treated at a tertiary referral center. The study group included children who received a Med-El multichannel cochlear implant and had used it for at least 18 months. The control group comprised generally healthy children with normal hearing and no history of chronic ear disease or otologic surgery. The main outcome measures, evaluated through a questionnaire sent by mail, were comparison of telephone use and speech comprehension over the telephone between the study and control groups. RESULTS: The median age of the study and control groups was 9 and 7 years, respectively (p = 0.12). There was a significant difference between the two groups in the reported rate of telephone use (mean 128 and 244 min/week, respectively, p = 0.006) and speech comprehension of familiar persons and strangers, which was highly significant among teenagers. The reported sound quality was similar for the two groups. PMID- 21034173 TI - External monitoring of buried radial forearm free flaps in hypopharyngeal reconstruction. AB - CONCLUSION: The radial forearm free flap (RFFF) is one of the optimal choices for hypopharyngeal reconstruction. Our series demonstrates that the technique of an indicator flap for the monitoring of the buried flap is simple, reliable, and inexpensive. The condition of the indicator flap can be easily interpreted by the physicians and the nursing staff. Therefore, the success rate of this microsurgical reconstruction may be improved. OBJECTIVES: The RFFF is increasingly applied in reconstruction of the hypopharynx after radical resection for advanced hypopharyngeal cancer. However, postoperative monitoring of the buried free flap is extremely difficult. We designed a small external component as an indicator flap to monitor the perfusion of the buried vascular pedicle. METHODS: Eight consecutive patients with hypopharyngeal cancer underwent radical surgery and hypopharyngeal reconstruction using RFFF at the Sun Yat-sen University Cancer Center between January 2005 and January 2007. The indicator flap was sutured to the surface of the neck for postoperative monitoring. RESULTS: All of the indicator flaps remained viable. One patient experienced vascular compromise and was successfully salvaged. The success rate of the buried flaps was 100%. Pharyngocutaneous fistula occurred in one patient. All patients resumed an oral diet eventually. PMID- 21034174 TI - Epidemiology of maternal injuries during pregnancy in a population-based study, 1997-2005. AB - BACKGROUND: Maternal injuries during pregnancy are common and can cause adverse pregnancy outcomes. We sought to describe factors related to injury during pregnancy. METHODS: We analyzed data from the National Birth Defects Prevention Study (NBDPS), a population-based, case-control study of birth defects in 10 U.S. states. We estimated the proportion of control mothers, a random sample of mothers delivering infants without major birth defects in the study regions, who reported an injury during pregnancy. We assessed associations with maternal and paternal characteristics using logistic regression to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CI). RESULTS: Between October 1997 and December 2005, 490 (7.4%) of 6609 mothers reported 527 injuries during pregnancy. Falls caused over half of reported injuries during pregnancy (51.6%), and 9.5% of reported injuries were intentionally inflicted. Mothers who reported an injury during pregnancy were more likely to be aged <18 years vs. 18-29 years (aOR 2.84, 95% CI 1.54-5.23) and less likely to be aged >=30 years (aOR 0.67, 95% CI 0.51 0.89). They were more likely to use alcohol during pregnancy (aOR for nonbinge drinking 1.38, 95% CI 1.05-1.81), to smoke during pregnancy (aOR 1.37, 95% CI 1.02-1.85), to have epilepsy (aOR 3.31, 95% CI 1.48-7.38), and to be employed (aOR 1.44, 95% CI 1.08-1.93) than mothers who did not report an injury. CONCLUSIONS: We identified several factors associated with maternal injury during pregnancy, an important step in identifying women who may be at higher risk and in designing interventions to prevent injuries during pregnancy. PMID- 21034175 TI - Differences between gynecologists and primary care physicians in hormone therapy prescribing: why they matter. PMID- 21034176 TI - Efficacy and safety of netilmycin/dexamethasone preservative-free and tobramycin/dexamethasone-preserved fixed combination in patients after cataract surgery. AB - PURPOSE: To compare the efficacy and safety of preservative-free Netilmycin/Dexamethasone with that of preserved Tobramycin/Dexamethasone, postcataract surgery. METHODS: Prospective, randomized, single-blind study on patients submitted to phacoemulsification. During preoperatory visits, at 7 and 21 days conjunctival hyperemia, corneal edema, Tyndall, Shirmer I, corneal and conjunctival lissamine green and fluorescein staining, and intraocular pressure (IOP) were recorded. Postoperative pain (at day 7) and the subjective tolerability (at day 21) were investigated. RESULTS: Eighty patients completed the study and the data collected were analyzed (44 on Netilmycin/Dexamethasone). Regarding the primary efficacy variable, intraocular inflammation, no microbial events were recorded, but aqueous flare was significantly lower with Tobramycin/Dexamethasone at 1 week (P = 0.002). Regarding secondary efficacy variables, conjunctival hyperemia was lower in patients under Tobramycin/Dexamethasone (P < 0.001), but corneal edema and ocular pain were similar. Regarding safety, no significant differences on ocular surface status were recorded. Both formulations were well tolerated, but Tobramycin/Dexamethasone caused an increased IOP at 1 week (P < 0.0001). CONCLUSIONS: Both the studied fixed combinations are safe and effective in controlling postoperative inflammation and preventing postoperative ocular infections. Tobramycin/Dexamethasone has a quicker anti-inflammatory effect but needs IOP monitoring. Further studies on more patients using a sounder scientific design are needed to confirm our findings. PMID- 21034177 TI - Bimatoprost versus travoprost in an Egyptian population: a hospital-based prospective, randomized study. AB - PURPOSE: To compare the efficacy of bimatoprost and travoprost on intraocular pressure (IOP) reduction in an Egyptian population. METHODS: Patients with primary open-angle glaucoma or ocular hypertension were randomized to receive either bimatoprost 0.03% or travoprost 0.004% once daily. IOPs were measured at baseline; 2 weeks; and 1, 2, 4, and 6 months using Goldman applanation tonometery. RESULTS: Seventy-two patients were included: 34 and 38 (P = 0.142) with a baseline mean IOP = 26.52 +/- 5.185 and 26.36 +/- 1.605 mm Hg (P = 0.629) for bimatoprost and travoprost, respectively. Both drops provided statistically significant IOP reductions from baseline at all visits (P < 0.001). Bimatoprost provided greater (nonsignificant) mean IOP reductions from baseline than travoprost at each visit. Mean IOP reductions was 8.77 mm Hg (33.39%) and 8.42 mm Hg (31.54%) at 2 weeks (P = 0.703), and 8.47 mm Hg (31.61%) and 7.84 mm Hg (29.50%) at 6 months (P = 0.536) for bimatoprost and travoprost, respectively. IOPs at 2 weeks were <=18 mm Hg in 20 (58.8%) versus 19 (50%) eyes (P = 0.603), and <=16 mm Hg in 12 (35%) versus 12 (32%) eyes (P = 0.456); and at 6 months <=18 mm Hg in 22 (65%) versus 14 (37%) eyes (P = 0.045), and <=16 mm Hg in 12 (35%) versus 7 (18%) eyes (P = 0.037) for bimatoprost and travoprost, respectively. Ocular adverse and clinical success occurred equally with both drops. CONCLUSION: Both drops lowered IOP effectively but bimatoprost showed a greater non significant reductions in mean IOP from baseline. PMID- 21034178 TI - Stressful life events, education, and metabolic syndrome in women: are they related? A study in first-degree relatives of type 2 diabetics. AB - BACKGROUND: Some reports show that the prevalence of metabolic syndrome is higher in poorly educated women. In our opinion, one probable reason for this is that these women experience more stressful events in their lives. We investigated the association between major stressful life events and the prevalence of metabolic syndrome and the effect of education on this relationship in women. METHODS: This cross-sectional study included 35- to 55-year-old women who were first-degree relatives of type 2 diabetics. They were questioned about stressful events in their lives, their physical activities, and basic characteristics. In addition waist circumference, blood pressure, fasting blood sugar, triglyceride, total and high-density lipoprotein cholesterol (HDL-C) were measured. Metabolic syndrome was defined according to Adult Treatment Panel III (ATP III) criteria, and the number of stresses was compared between two groups of participants with and without metabolic syndrome. RESULTS: Among the 351 study participants, the prevalence of metabolic syndrome was 28.9%. The mean number of stresses in the metabolic syndrome group was higher than in the nonmetabolic syndrome group at 3.82 +/- 2.67 and 3.14 +/- 2.35, respectively (P = 0.036). The prevalence of metabolic syndrome in subjects with eight or more stressful life events (46%) was greater compared to those who had experienced less than eight stresses (23.4%; P = 0.017). The relationship between stressful life events and the prevalence of metabolic syndrome was independent of the low level of education, but the prevalence of poorly educated women was associated with the number of stresses. CONCLUSION: Considering the probable association between stress and prevalence of metabolic syndrome, which itself increases the risk of cardiovascular diseases, educating high-risk people to cope with stresses may be beneficial in reducing the incidence of cardiovascular diseases and preventing the onset of metabolic syndrome. PMID- 21034179 TI - The role of bile acid sequestrants in the management of type 2 diabetes mellitus. AB - The prevalence of type 2 diabetes (T2DM) and cardiovascular disease (CVD) continues to escalate globally. There is now abundant clinical trial evidence that the optimal treatment of CVD risk factors, with lifestyle changes aimed at weight loss in most patients, and pharmacologic management of dyslipidemia and hyperglycemia, can help mitigate the CVD burden. Yet more than 50% of patients are still not achieving glycosylated hemoglobin (HbA1c) and low-density lipoprotein cholesterol (LDL-C) goals. Over the past 15 years, many novel and emerging drugs have made it possible to achieve optimal glycemic control, generally in combination therapy, without untoward effects of weight gain, hypoglycemia, and other adverse effects with traditional agents. Although the long-term efficacy and safety of some of the newer classes of agents are yet to be determined, bile acid sequestrants represent a unique long-standing class of agents. These drugs have the dual efficacy in glycemic control and LDL-C reduction, and an established record of long-term safety. Colesevelam HCl is the only drug approved for this dual indication and is an adjunct in the treatment of both hyperglycemia and hypercholesterolemia that frequently co-exist in adults with T2DM. PMID- 21034180 TI - Mood stabilizers in pregnancy: a systematic review. AB - OBJECTIVE: To undertake a systematic review of the effects of exposure to mood stabilizer medication in pregnancy, evaluating teratogenicity and other outcomes for mother and child. This was one of three concurrent systematic reviews of psychotropic medication exposure in pregnancy. METHOD: A systematic search was carried out of electronic databases, reference books and other sources for original research studies which examined the effects of commonly used mood stabilizers (sodium valproate, carbamazepine, lamotrigine and lithium carbonate) on pregnancy outcomes. These included malformations, pregnancy complications, neonatal complications and longer term developmental outcomes for children exposed. RESULTS: All mood stabilizers were found to be associated with a risk of malformation and perinatal complications. Studies which examined longer term neurodevelopmental outcomes found poorer outcomes for those children exposed to sodium valproate or polytherapy in pregnancy than for other individual AEDs. The data available for longer term child outcomes with lithium exposure is too limited to draw any conclusions. CONCLUSIONS: This review found that exposure in pregnancy to all four commonly used mood stabilizers may be teratogenic, and is associated with increased rates of pregnancy and neonatal complications. There was also more limited information that sodium valproate may be associated with poorer longer term child developmental outcomes. These findings must be balanced with the risk of relapse and poor pregnancy and child outcomes with untreated maternal bipolar disorder. The information obtained from these reviews of psychotropic medications will assist clinicians in managing women with mental illness in pregnancy. PMID- 21034181 TI - Antidepressants in pregnancy: a systematic review. AB - Part of three systematic reviews on the effects of psychotropic medication exposure in pregnancy, this paper critically reviews the literature on adverse effects of antidepressant use during pregnancy, and derives recommendations for clinical practice. Electronic databases were searched for original research studies examining the effects of gestational exposure to antidepressants on pregnancy, neonatal and longer-term developmental outcomes. Most results were derived from cohort (prospective and retrospective) and casecontrol studies. There were no randomized controlled trials. Congenital malformations: 35 studies identified, 12 demonstrated a significant association between antidepressant use in early pregnancy and congenital malformations. Pregnancy outcomes: 35 articles identified, outcomes measured rates of spontaneous abortion (4 out of 7 studies reporting elevated risk), preterm birth (15 out of 19 reporting elevated risk) and abnormal birth weight (8 out of 23 reporting elevated risk). Neonatal outcomes: 17 controlled studies including one meta-analysis were identified concerning neonatal adaptation. 15 studies showed an association between gestational exposure to antidepressants and neonatal adaptation difficulties. Three studies examined an association between selective serotonin reuptake inhibitor (SSRI) exposure and persistent pulmonary hypertension in the neonate with conflicting results. Longer-term developmental outcomes: 6 of 7 studies comparing developmental outcomes of children exposed to antidepressants in utero with non- exposed children reported no significant differences. Most of these medications remain relatively safe in pregnancy, but some significant areas of concern exist, particularly some evidence of higher risk of preterm birth, neonatal adaptation difficulties and congenital cardiac malformations (with paroxetine). The impact of these findings on the risk-benefit analysis when treating pregnant women with antidepressants is discussed. PMID- 21034182 TI - The complementarity of two major Australian primary mental health care initiatives. AB - OBJECTIVE: Two pivotal Australian Government primary mental health reforms are the Access to Allied Psychological Services (ATAPS) projects, introduced in July 2001 and implemented by Divisions of General Practice, and the Better Access to Psychiatrists, Psychologists and GPs through the Medicare Benefits Schedule (Better Access) programme, introduced in November 2006. This research explores the reciprocal impact of the uptake of psychological treatment delivered by these two initiatives and the impact of location (rurality and socioeconomic profile) on the uptake of both programmes since the inception of the Better Access programme. ATAPS session delivery, before and after the introduction of the Better Access program, is also examined. METHOD: General Practice Division-level data sources included a minimum dataset containing uptake data of ATAPS services, Medicare Benefits Schedule uptake data supplied by the Medicare Benefits Branch of the Department of Health and Ageing, a Rural, Remote and Metropolitan Area classification, and Indices for Relative Socio Economic Disadvantage (IRSD). Regression analyses were conducted to examine the reciprocal impact of the two programmes and the impact of rurality and socioeconomic status up to December 2008. RESULTS: A dramatic uptake of Better Access sessions, particularly in urban areas, coincided with a temporary reduction in sessions provided under ATAPS, with an overall small positive relationship detected between the two programmes. A greater proportion of ATAPS sessions (45%) have been delivered in rural areas compared with Better Access (18%). The combination of socioeconomic profile, rurality, and Better Access sessions accounted for a small but significant percentage of variance (7%) in the number of ATAPS sessions delivered, with a non significant independent contribution of Better Access sessions to the prediction of ATAPS sessions. Weak but significant relationships between ATAPS sessions and each of socioeconomic profile (r = 0.22) and rurality (r = -0.24), respectively, were identified. In comparison, socioeconomic profile, rurality, and ATAPS sessions accounted for a much larger and significant percentage of variance (46%) in number of Better Access sessions delivered, with a non-significant independent contribution of ATAPS sessions to the prediction of Better Access sessions. Moderate significant relationships between Better Access sessions and each of socioeconomic profile (r = 0.46) and rurality (r = -0.66), respectively, were identified. The introduction of Better Access appears to have halted the steady increase in the number of ATAPS sessions previously observed. This finding should be interpreted alongside the fact that ATAPS funding is capped. CONCLUSIONS: The findings are policy relevant. ATAPS projects have been successfully providing equity of geographic and socioeconomic access for consumers most in need of subsidized psychological treatment. The uptake of psychological treatment under Better Access has been dramatic, suggesting that the programme is addressing an unmet need. PMID- 21034183 TI - Depression, anxiety disorders and Type D personality as risk factors for delirium after cardiac surgery. AB - OBJECTIVES: To determine the prognostic risk of incident delirium after cardiac surgery attributable to preoperative affective disorders and Type D personality. METHODS: Patients awaiting elective coronary revascularization surgery (N = 158; 20.9% female; 11.4% concomitant valve surgery; age M = 64.7, SD = 10.6) underwent the structured MINI International Neuropsychiatric Interview and completed a measure of Type D personality. Postoperative incident delirium was established prior to discharge from the index hospitalization with structured psychiatric interview. RESULTS: The prevalence of psychiatric disorders before cardiac surgery was 17.1% for major depression, 7.6% for panic disorder, 10.1% for generalized anxiety disorder, and 13.3% for Type D personality, while there were 49 (31% of total) cases of delirium after surgery. After adjustment for sex, older age, cross-clamp time, haemoglobin (Hb) and psychotropic drug use, major depression was significantly associated with delirium, odds ratio (OR) = 3.86 (95% confidence interval (CI) 1.42 to 10.52, p = 0.001). Adjustment for clinical covariates suggested that Type D personality was not significantly associated with delirium, OR = 2.85 (95%CI 0.97 to 8.38, p = 0.06). CONCLUSIONS: Major depression was significantly associated with incident delirium after cardiac surgery. These findings suggest that the risk of incident delirium attributable to major depression was not merely a reflection of common diagnostic features in prospectively examined cardiac surgery patients. PMID- 21034185 TI - People with mental illness can tackle tobacco. AB - OBJECTIVE: To evaluate a smoking reduction and cessation intervention tailored for people with significant disability associated with mental illness. METHOD: The intervention was a 10 week group programme, which tailored smoking cessation interventions to the needs of people living with mental illness. It was facilitated by mental health workers and peer workers and was promoted through mental health services, general practitioners and the Quitline phone service. Participants were people living with mental illness who had asked for help to quit or reduce their tobacco use. Participants were interviewed before starting the course, twice during the course and at 3, 6 and 12 months post course completion. RESULTS: Overall, 226 people expressed interest, 183 attended at least one session of the course and 105 attended at least 10 sessions. Of the 183 participants, 79.8% reported they did not smoke for at least 24 hours, with 30.6% stopping for at least 30 days. At the 12 month follow up 16.6% of participants reported they were not smoking. Of the 105 participants who attended at least 10 sessions of the course, 85.7% reported they did not smoke for at least 24 hours and 37.1% stopping for at least 30 days. At 12 month follow up 21.3% reported they were not smoking. Cigarettes smoked per day declined among those who did not quit, and was still significantly lower after 12 months. Motivation to try to quit was high among those still smoking at 12 months, with 83.9% wanting to try again to quit. CONCLUSIONS: This programme has shown many people with significant disability associated with mental illness are motivated to attend a smoking reduction and cessation group programme. A programme tailored to meet the specific needs of this group can be effective in helping many to quit or reduce their tobacco use. PMID- 21034184 TI - Social phobia: further evidence of dimensional structure. AB - OBJECTIVE: Social phobia is a common mental disorder associated with significant impairment. Current research and treatment models of social phobia rely on categorical diagnostic conceptualizations lacking empirical support. This study aims to further research exploring whether social phobia is best conceptualized as a dimension or a discrete categorical disorder. METHODS: This study used three distinct taxometric techniques (mean above minus below a cut, maximum Eigen value and latent mode) to explore the latent structure of social phobia in two large epidemiological samples, using indicators derived from diagnostic criteria and associated avoidant personality traits. RESULTS: Overall, outcomes from multiple taxometric analyses supported dimensional structure. This is consistent with conceptualizations of social phobia as lying on a continuum with avoidant personality traits. CONCLUSIONS: Support for the dimensionality of social phobia has important implications for future research, assessment, treatment, and public policy. PMID- 21034186 TI - Australian Schizophrenia Research Bank: a database of comprehensive clinical, endophenotypic and genetic data for aetiological studies of schizophrenia. AB - OBJECTIVE: This article describes the establishment of the Australian Schizophrenia Research Bank (ASRB), which operates to collect, store and distribute linked clinical, cognitive, neuroimaging and genetic data from a large sample of people with schizophrenia and healthy controls. METHOD: Recruitment sources for the schizophrenia sample include a multi-media national advertising campaign, inpatient and community treatment services and non-government support agencies. Healthy controls have been recruited primarily through multi-media advertisements. All participants undergo an extensive diagnostic and family history assessment, neuropsychological evaluation, and blood sample donation for genetic studies. Selected individuals also complete structural MRI scans. RESULTS: Preliminary analyses of 493 schizophrenia cases and 293 healthy controls are reported. Mean age was 39.54 years (SD = 11.1) for the schizophrenia participants and 37.38 years (SD = 13.12) for healthy controls. Compared to the controls, features of the schizophrenia sample included a higher proportion of males (cases 65.9%; controls 46.8%), fewer living in married or de facto relationships (cases 16.1%; controls 53.6%) and fewer years of education (cases 13.05, SD = 2.84; controls 15.14, SD = 3.13), as well as lower current IQ (cases 102.68, SD = 15.51; controls 118.28, SD = 10.18). These and other sample characteristics are compared to those reported in another large Australian sample (i.e. the Low Prevalence Disorders Study), revealing some differences that reflect the different sampling methods of these two studies. CONCLUSION: The ASRB is a valuable and accessible schizophrenia research facility for use by approved scientific investigators. As recruitment continues, the approach to sampling for both cases and controls will need to be modified to ensure that the ASRB samples are as broadly representative as possible of all cases of schizophrenia and healthy controls. PMID- 21034187 TI - Managing pregnant women with serious mental illness: using the Edinburgh Postnatal Depression Scale as a marker of anxiety and depressive symptoms. AB - OBJECTIVE: To examine the course of depressive and anxiety symptoms using serial measurements of the Edinburgh Postnatal Depression Scale (EPDS) in pregnant women with serious mental illness (SMI) attending a specialist multi-disciplinary antenatal clinic in Perth, Western Australia. METHOD: A retrospective review of case notes was undertaken for 48 Western Australian pregnant women with schizophrenia and related psychoses and bipolar affective disorders who attended the Childbirth and Mental Illness (CAMI) antenatal clinic between December 2007 and November 2009. Of these patients, 27 completed the EPDS at booking (first appointment) and at 32 weeks gestation. Additional variables collected were demographic data, gestation at booking, and attendance rates for these 27 women, and for comparison another 21 women who did not complete the EPDS for one or both screening periods. RESULTS: Mean total EPDS score decreased from 12.2 (SD 7.6) at booking to 8.5 (SD 6.4) at 32 weeks gestation (p = 0.007). Overall mean attendance rates and number of appointments were similar to the non-SMI population and in keeping with standard guidelines. CONCLUSIONS: We speculate from these preliminary findings that being managed by a consistent small multi disciplinary team and knowing that they will be supported throughout their pregnancy could lead to improvement of anxiety and depressive symptoms in pregnant women with SMI, and has the potential to increase their attendance for antenatal care. PMID- 21034188 TI - Psychiatric disorders and unmet needs in Australian police cells. AB - OBJECTIVE: To determine the prevalence of current psychiatric disorders and unmet needs in a sample of police cell detainees in Victoria. METHOD: A cross-sectional descriptive study was conducted, including data linkage with the Victoria Police database and the Victorian Psychiatric Case Register. In Melbourne, Australia, 150 detainees were recruited from two busy metropolitan police stations. Outcome measures included estimated rates of psychiatric disorders, using the Structured Clinical Interview for DSM-IV-TR, and individual needs, using the Camberwell Assessment of Need - Forensic Version. RESULTS: One quarter (n = 32, 25.4%) of detainees had a prior admission to a psychiatric hospital, and three quarters met current criteria for a diagnosable mental disorder. The most common disorders were substance dependence (n = 81, 54%) and mood disorders (n = 60, 40%). A third met diagnostic criteria for both a mental illness and a substance use disorder. The odds of being classified with mood (OR = 10.1), anxiety (OR = 2.2), psychotic (OR = 15.4) and substance use disorders (OR = 26.3) were all significantly higher in the current sample as compared with the general population. Detainees with a mental illness identified significantly more needs and significantly more unmet needs (e.g. psychological distress) than those who did not rate as having a current mental illness. CONCLUSIONS: There remains a pressing need to evaluate standardized screening tools for mental illnesses in police cells to provide timely access to assessment and treatment services. The need for functional interagency collaborations are highlighted and discussed. PMID- 21034189 TI - Apparent antidepressant over-prescribing to older Australians might reflect invalid CIDI depression diagnoses. PMID- 21034190 TI - Prevalence and treatment of late life depression. PMID- 21034191 TI - A Dutch guideline for the use of clozapine. PMID- 21034192 TI - Clinical outcomes associated with depression, anxiety and social support among cardiac rehabilitation attendees. PMID- 21034193 TI - Can information technology improve the performance of remote monitoring systems? AB - Despite some clinical, economic, and other qualitative advantages associated with remote cardiac device monitoring systems, one of the main challenges concerns the management of the out-of-hospital data. Manual updating of hospital databases with the data stored in the manufacturers' servers increases time requirements and may introduce mistakes in the entries. The use of communication standards such as Health Level 7 for data interchange could provide a safe and easy way to access patient and device information. The present study of 38 patients was carried out with the Carelink(r) remote monitoring technology. A formal process for remote cardiac device monitoring was established, including some features in the Arrhythmias Information System: mobile phone and e-mail were included for communication between patients and hospital, with a new gateway for automatic message sending. Device reports generated through the manufacturer's application were attached to the patient's record. Once the information concerning the transmission session was reviewed, the physician made a medical report, which was sent via post and e-mail to the patient. A new interface was created for Health Level 7 communication with the manufacturers' applications, so that the Arrhythmias Information System could automatically interchange information concerning the device and/or the patient when this kind of communication system is available. The volume of data generated by system warning alerts and transmission sessions makes it very difficult to meet the hospital database updating requirements. Standard-based communication between hospital and manufacturers' applications is fundamental to automatic and reliable update of data. PMID- 21034194 TI - Pre- and post-conjugate vaccine epidemiology of pneumococcal serotype 6C invasive disease and carriage within Navajo and White Mountain Apache communities. AB - BACKGROUND: A second-generation 13-valent pneumococcal conjugate vaccine, PCV13, was recently licensed. Although PCV13 includes serotype 6A, the usefulness of that antigen may be limited by the emergence of a new serotype, 6C, which was identified among isolates initially characterized (Quellung reaction) as serotype 6A. The epidemiology of serotype 6C prior to and after 7-valent PCV (PCV7) introduction is incompletely understood. METHODS: We analyzed conventionally serotyped 6A (CS6A) pneumococci from invasive disease case patients of all ages and carriage isolates from children and adults obtained in population-based studies among Navajo and White Mountain Apache communities during 1994-2009. Samples were tested by triplex polymerase chain reaction to resolve serotypes 6C and 6A. RESULTS: A total of 74 invasive CS6A episodes occurred. All were retyped by polymerase chain reaction; 40 (54.1%) were serotype 6C. The mean annual incidence of serotype 6C invasive disease was 0.3 (95% confidence interval, 0.03 0.9), 0.7 (95% confidence interval, 0.2-1.3), and 1.5 (95% confidence interval, 1.0-2.1) cases per 100,000 population in the years prior to the PCV7 efficacy trial, during the time the PCV7 trial was conducted, and following PCV7 introduction and routine use, respectively (P = .01). In the routine vaccination era, 76% of invasive CS6As were serotype 6C; nearly all cases occurred in adults. The proportion of serotype 6C among CS6A carriage isolates increased from 42% to 61% to 94% in the prevaccine, early vaccine, and routine vaccination eras, respectively. CONCLUSION: In the PCV7 routine use era, virtually all serogroup 6 invasive pneumococcal disease and carriage strains among Navajo and White Mountain Apache communities are 6C. Monitoring and evaluation of this and other emerging serotypes among invasive disease and carriage isolates is warranted. PMID- 21034195 TI - Predicting the need for radiologic imaging in adults with febrile urinary tract infection. AB - BACKGROUND: Radiologic evaluation of adults with febrile urinary tract infection (UTI) is frequently performed to exclude urological disorders. This study aims to develop a clinical rule predicting need for radiologic imaging. METHODS: We conducted a prospective, observational study including consecutive adults with febrile UTI at 8 emergency departments (EDs) in the Netherlands. Outcomes of ultrasounds and computed tomographs of the urinary tract were classified as "urgent urological disorder" (pyonephrosis or abscess), "nonurgent urologic disorder," "normal," and "incidental nonurological findings." Urgent and nonurgent urologic disorders were classified as "clinically relevant radiologic findings." The data of 5 EDs were used as the derivation cohort, and 3 EDs served as the validation cohort. RESULTS: Three hundred forty-six patients were included in the derivation cohort. Radiologic imaging was performed for 245 patients (71%). A prediction rule was derived, being the presence of a history of urolithiasis, a urine pH >=7.0, and/or renal insufficiency (estimated glomerular filtration rate, <=40 mL/min/1.73 m(3)). This rule predicts clinically relevant radiologic findings with a negative predictive value (NPV) of 93% and positive predictive value (PPV) of 24% and urgent urological disorders with an NPV of 99% and a PPV of 10%. In the validation cohort (n = 131), the NPV and PPV for clinically relevant radiologic findings were 89% and 20%, respectively; for urgent urological disorders, the values were 100% and 11%, respectively. Potential reduction of radiologic imaging by implementing the prediction rule was 40%. CONCLUSIONS: Radiologic imaging can selectively be applied in adults with febrile UTI without loss of clinically relevant information by using a simple clinical prediction rule. PMID- 21034196 TI - HIV treatment as prevention and "the Swiss statement": in for a dime, in for a dollar? PMID- 21034198 TI - Epidemic of group A Streptococcus M/emm59 causing invasive disease in Canada. AB - BACKGROUND: The incidence of invasive group A Streptococcus (GAS) disease can vary over time and geographic region, possibly reflecting the population's susceptibility to particular strains but also variation in the predominant M/emm types. Canadian surveillance documented an epidemic of an uncommon M/emm59 type from 2006 to 2009. METHODS: Invasive GAS isolates are submitted by Public Health Laboratories in Canada to the National Centre for Streptococcus for M/emm typing. Patient age, sex, geographic location, and the anatomical source of isolate are provided with the isolate. When it was recognized that M/emm59 strains were increasing in prevalence, clinical information was collected on M/emm59 cases captured in Alberta and compared with cases of other M/emm types occurring in this province. RESULTS: From January 2006 through December 2009, 539 (13.0%) of 4150 invasive GAS cases were identified as M/emm59: 164 from British Columbia, 146 from Alberta, 62 from Saskatchewan, 82 from Manitoba, 68 from Ontario, 14 from Quebec, 1 from New Brunswick, 1 from Newfoundland, 1 from Yukon, and 1 from Nunavut. The predominant clinical presentation was bacteremia (45.0%) followed by cellulitis (41.4%). Compared with concurrent cases of invasive GAS disease caused by all other M/emm types, identified risk factors for M/emm59 disease were alcohol abuse (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.4-3.8), homelessness (OR, 2.0; 95% CI, 1.2-3.4), hepatitis C virus infection (OR, 2.0; 95% CI, 1.1-3.5), and illicit drug use (OR, 1.7; 95% CI, 1.0-3.0). CONCLUSIONS: Western Canada has witnessed the rapid emergence of a rare GAS strain causing invasive disease predominately in a select population of disadvantaged persons. PMID- 21034197 TI - Risk factors for infection and colonization with community-associated methicillin resistant Staphylococcus aureus in the Los Angeles County jail: a case-control study. AB - BACKGROUND: Community-associated methicillin-resistant Staphylococcus aureus (MRSA) infections and outbreaks occur in correctional facilities, such as jails and prisons. Spread of these infections can be extremely difficult to control. Development of effective prevention protocols requires an understanding of MRSA risk factors in incarcerated persons. METHODS: We performed a case-control study investigating behavioral risk factors associated with MRSA infection and colonization. Case patients were male inmates with confirmed MRSA infection. Control subjects were male inmates without skin infection. Case patients and control subjects completed questionnaires and underwent collection of nasal swab samples for culture for MRSA. Microbiologic analysis was performed to characterize recovered MRSA isolates. RESULTS: We enrolled 60 case patients and 102 control subjects. Of the case patients, 21 (35%) had MRSA nasal colonization, compared with 11 control subjects (11%) (P .001). Among MRSA isolates tested, 100% were the USA300 strain type. Factors associated with MRSA skin infection included MRSA nares colonization, lower educational level, lack of knowledge about "Staph" infections, lower rate of showering in jail, recent skin infection, sharing soap with other inmates, and less preincarceration contact with the health care system. Risk factors associated with MRSA colonization included antibiotic use in the previous year and lower rate of showering. CONCLUSIONS: We identified several risks for MRSA infection in male inmates, many of which reflected preincarceration factors, such as previous skin infection and lower educational level. Some mutable factors, such as showering frequency, knowledge about Staph, and soap sharing, may be targets for intervention to prevent infection in this vulnerable population. PMID- 21034199 TI - Probable invasive aspergillosis without prespecified radiologic findings: proposal for inclusion of a new category of aspergillosis and implications for studying novel therapies. AB - BACKGROUND: The European Organization for Research and Treatment of Cancer (EORTC) and the Mycosis Study Group (MSG) definition of invasive aspergillosis used in clinical trials lacks sensitivity. We hypothesize that giving lower weight to the prespecified radiologic findings in patients with a positive serum galactomannan index test result will improve the definition's diagnostic sensitivity. METHODS: The medical records of 121 patients with 125 cases of invasive aspergillosis treated at a referral cancer institute from January 2003 through December 2009 were reviewed. Aspergillosis was diagnosed as EORTC-MSG proven or probable (controls, 83) or probable invasive aspergillosis without prespecified radiologic criteria (cases, 42). The latter differed from the former by the inclusion of patients whose pulmonary infiltrates, although well described in invasive aspergillosis, do not fulfill EORTC-MSG invasive aspergillosis requirements. The host, clinical, and mycologic characteristics and survival of cases and controls served as end points. RESULTS: A total of 114 (91%) of 125 patients had multiple myeloma. Patients had a median age was 65 years (range, 26 81 years), and 74 were male. All had received antineoplastic therapy, including stem cell transplantation (58 [46%]). Aspergillosis involved lungs (88 patients), sinuses (9 patients), or both (28 patients). Except for higher median baseline platelet count and shorter duration of neutropenia among cases, there were no statistically significant differences between groups on all predefined end points, including 4-, 6-, and 12-week survival. Eleven of 26 cases were reclassified as controls on the basis of subsequent imaging. CONCLUSIONS: Except for less well-circumscribed consolidations, the host, clinical, radiologic, and mycologic characteristics and outcome of patients with probable invasive aspergillosis but without prespecified radiologic criteria are similar to those with EORTC-MSG invasive aspergillosis. Enrolling such patients in clinical trials of novel therapies will increase the pool of eligible study participants and improve trial speed and efficiency. PMID- 21034201 TI - Chest computed tomography versus serum galactomannan enzyme immunoassay for the diagnosis of probable invasive aspergillosis: to be decided. PMID- 21034200 TI - Frequency and determinants of unprotected sex among HIV-infected persons: the Swiss HIV cohort study. AB - BACKGROUND: Access to antiretroviral therapy may have changed condom use behavior. In January 2008, recommendations on condom use for human immunodeficiency virus (HIV)-positive persons were published in Switzerland, which allowed for unprotected sex under well-defined circumstances ("Swiss statement"). We studied the frequency, changes over time, and determinants of unprotected sex among HIV-positive persons. METHODS: Self-reported information on sexual preference, sexual partners, and condom use was collected at semi-annual visits in all participants of the prospective Swiss HIV Cohort Study from April 2007 through March 2009. Multivariable logistic regression models were fit using generalized estimating equations to investigate associations between characteristics of cohort participants and condom use. FINDINGS: A total of 7309 participants contributed to 21,978 visits. A total of 4291 persons (80%) reported sexual contacts with stable partners, 1646 (30%) with occasional partners, and 557 (10%) with stable and occasional partners. Of the study participants, 5838 (79.9%) of 7309 were receiving antiretroviral therapy, and of these, 4816 patients (82%) had a suppressed viral load. Condom use varied widely and differed by type of partner (visits with stable partners, 10,368 [80%] of 12,983; visits with occasional partners, 4300 [88%] of 4880) and by serostatus of stable partner (visits with HIV-negative partners, 7105 [89%] of 8174; visits with HIV-positive partners, 1453 [48%] of 2999). Participants were more likely to report unprotected sex with stable partners if they were receiving antiretroviral therapy, if HIV replication was suppressed, and after the publication of the "Swiss statement." Noninjection drug use and moderate or severe alcohol use were associated with unprotected sex. CONCLUSIONS: Antiretroviral treatment and plasma HIV RNA titers influence sexual behavior of HIV-positive persons. Noninjection illicit drug and alcohol use are important risk factors for unprotected sexual contacts. PMID- 21034202 TI - The Italian version of the Sickness Impact Profile-Roland Scale for chronic pain: cross-cultural adaptation, reliability, validity and sensitivity to change. AB - PURPOSE: As no adapted form of the 23-item Sickness Impact Profile (SIP)-Roland Scale for patients with chronic pain has ever been validated in the Italian population, the aim of this study was to translate, culturally adapt and validate an Italian version. METHODS: The development of the Italian version involved translation and back-translation, a final review by an expert committee and the testing of the pre-final version to establish its correspondence with the original. The psychometric testing included testing reliability by internal consistency (Cronbach's alpha) and test-retest repeatability (intraclass coefficient correlation; ICC), construct validity by comparison with an 11-point pain intensity numerical rating scale (NRS; Pearson's correlation) and the Short Form Health Survey (SF-36; Pearson's correlation) and sensitivity to change by calculating the minimum detectable change (MDC). RESULTS: It took 3 months to obtain a shared version of the scale, which was administered to 243 subjects and proved to be satisfactorily acceptable. It had a high degree of internal consistency (alpha = 0.860) and test-retest reliability (ICC = 0.972). Construct validity testing revealed a moderate correlation with the NRS (r = 0.418), close correlations with the SF-36 physical subscales and moderate-poor correlations with the mental and social subscales; the MDC was 2.33. CONCLUSIONS: The SIP Roland scale was successfully translated into Italian, showing satisfactory psychometric properties. The measure can be recommended for use in research and clinical practice to improve the assessment of physical dysfunction in subjects with chronic pain. PMID- 21034203 TI - Use of the International Classification of Functioning, Disability and Health to identify preliminary comprehensive and brief core sets for Guillain Barre syndrome. AB - PURPOSE: To identify the preliminary comprehensive and brief core sets for Guillain Barre syndrome (GBS), in a Delphi process using the International Classification of Functioning, Disability and Health (ICF). METHOD: Focus groups and a consensus process were used to identify ICF core sets for GBS. This included: preliminary ICF studies; empirical patient data collection for 77 GBS participants; review of the evidence base and treatment in GBS literature followed by a Delphi exercise with 23 physicians and allied health professionals in Melbourne, Australia. RESULTS: The expert consensus selected 99 second level ICF categories (in three rounds) which identify health domains relevant to GBS for multidisciplinary assessment. These domains were consistent with current practice and existing GBS literature. The comprehensive core set includes: 27 (23%) categories from the component 'body function', 7 (12%) categories from 'body structures', 43 (36%) from 'activities and participation' and 22 (29%) from the component 'environmental' factors. The brief set comprised 20 categories, 20% of categories in the comprehensive core set. CONCLUSION: The core set categories for GBS-related health need to be addressed in multidisciplinary care programs. Future clinical 'rating' of this set may facilitate scale development using the ICF in GBS. Further research is needed to confirm the generalisability of this set in clinical settings. PMID- 21034204 TI - Thermoregulation during flight: body temperature and sensible heat transfer in free-ranging Brazilian free-tailed bats (Tadarida brasiliensis). AB - Bat wings are important for thermoregulation, but their role in heat balance during flight is largely unknown. More than 80% of the energy consumed during flight generates heat as a by-product, and thus it is expected that bat wings should dissipate large amounts of heat to prevent hyperthermia. We measured rectal (T(r)) and surface (T(s)) temperatures of Brazilian free-tailed bats (Tadarida brasiliensis) as they emerged from and returned to their daytime roosts and calculated sensible heat transfer for different body regions (head, body, wings, and tail membrane). Bats' T(r) decreased from 36.8 degrees C during emergence flights to 34.4 degrees C during returns, and T(s) scaled positively with ambient temperature (T(a)). Total radiative heat loss from bats was significantly greater for a radiative sink to the night sky than for a sink with temperature equal to T(a). We found that free-ranging Brazilian free-tailed bats, on average, do not dissipate heat from their wings by convection but instead dissipate radiative heat (L) to the cloudless night sky during flight ([Formula: see text] W). However, within the range of T(a) measured in this study, T. brasiliensis experienced net heat loss between evening emergence and return flights. Regional hypothermia reduces heat loss from wings that are exposed to potentially high convective fluxes. Additional research is needed to establish the role of wings in evaporative cooling during flight in bats. PMID- 21034205 TI - Decrease in suicide rates after a change of policy reducing access to firearms in adolescents: a naturalistic epidemiological study. AB - The use of firearms is a common means of suicide. We examined the effect of a policy change in the Israeli Defense Forces reducing adolescents' access to firearms on rates of suicide. Following the policy change, suicide rates decreased significantly by 40%. Most of this decrease was due to decrease in suicide using firearms over the weekend. There were no significant changes in rates of suicide during weekdays. Decreasing access to firearms significantly decreases rates of suicide among adolescents. The results of this study illustrate the ability of a relatively simple change in policy to have a major impact on suicide rates. PMID- 21034206 TI - The effectiveness of family-based cognitive-behavior grief therapy to prevent complicated grief in relatives of suicide victims: the mediating role of suicide ideation. AB - Grief interventions are more effective for high risk individuals. The presence of suicide ideation following suicide bereavement was examined to determine whether it indicates a high risk status. Using data from a randomized controlled trial (n = 122) on the effectiveness of cognitive-behavior therapy, the effect of suicide ideation on the effectiveness of grief therapy on the bereavement outcome at 13 months post loss was examined. Results show that suicide ideators more often have a history of mental disorder and suicidal behavior than non-ideators, and suicide ideation indicates a high risk for adverse bereavement outcome. Grief therapy likely reduces the risk of maladaptive grief reactions among suicide ideators. Therefore, suicide ideators may benefit from grief therapy following a loss through suicide. PMID- 21034207 TI - College students' intentions to seek help for suicidal ideation: accounting for the help-negation effect. AB - Prior research has identified a negative association between suicidal ideation and help-seeking, a phenomenon called "help-negation." Help-negation has been documented to occur for both professional and nonprofessional sources of help. In this study help-seeking attitudes, stigma concerns, and perceptions of social support were examined as possible mediators of help-negation. Data were collected from a nonclinical sample of college undergraduates at a midwestern university (N = 321). Findings provided partial support for the mediation hypotheses. Help seeking attitudes and stigma were significant predictors of help-seeking intentions (beta = .34 and beta = -.17, p < .05, respectively), but did not mediate help-negation for professional sources. Perceptions of social support, on the other hand, fully mediated help-negation for nonprofessional sources (beta = .27, p < .05). PMID- 21034208 TI - Sex differences in developmental trends of suicide ideation, plans, and attempts among European American adolescents. AB - Although suicide ideation, plans, and attempts increase during adolescence, it remains unclear whether boys' and girls' risk for these outcomes peaks at different ages. We used longitudinal categorical data (never, once, 2+ times) from the Family Transitions Project (N = 1,248 rural European Americans, ages 11 19) to investigate whether yearly prevalence rates of adolescent suicidal episodes follow different patterns by sex. Multiple-group growth models revealed that peak levels of past-year ideation and plans occurred during mid adolescence for girls, but slowly increased through late adolescence for boys. We found that prevalence patterns for attempts were very similar for boys and girls, with both increasing through mid adolescence and then declining, although girls' risk declined slightly more rapidly. This information may help alert gatekeepers to developmental periods during which boys and girls are particularly vulnerable to suicide-related experiences, and also may help inform the timing of preventive efforts. PMID- 21034210 TI - Lives and deaths: Biographical notes on selections from the works of Edwin S. Shneidman. AB - Edwin S. Shneidman (DOB: 1918-05-13; DOD: 2009-05-15) is a father of contemporary suicidology. His work reflects the intensive study of lives lived and deaths, especially suicides, and is the mirror to his mind. His contributions can be represented by five categories: psychological assessment, logic, Melville and Murray, suicide, and death. His works on suicide can be further divided into five parts: definitional and theoretical, suicide notes, administrative and programmatic, clinical and community, and psychological autopsy and postvention. In this article, not only are the selected works explicated, but also Dr. Shneidman's rather personal biographical notes are shared to allow the reader to understand one more unique individual's life lived, and his death: Edwin S. Shneidman. PMID- 21034209 TI - Relationships of suicide ideation with cause-specific mortality in a longitudinal study of South Koreans. AB - Using 7-year mortality follow-up data (n = 341) from the 1998 National Health and Nutrition Examination Surveys of South Korean individuals (N = 5,414), the authors found that survey participants with suicide ideation were at increased risk of suicide mortality during the follow-up period compared with those without suicide ideation. The cause-specific analyses showed that, in men, suicide ideation was significantly associated with mortality due to cardiovascular disease, external causes, and other causes. However, there was no significant association between suicide ideation and cause-specific mortality in women. The relationship between suicide ideation and cause-specific mortality in men was not fully explained by baseline health status, socioeconomic status, health behavior, or psychosocial factors. PMID- 21034212 TI - Surrogate endpoints in suicide research. AB - Surrogate endpoints frequently substitute for rare outcomes in research. The ability to learn about completed suicides by investigating more readily available and proximate outcomes, such as suicide attempts, has obvious appeal. However, concerns with surrogates from the statistical science perspective exist, and mounting evidence from psychometric, neurochemical, genetic, and neuroimaging studies suggests that surrogates may be particularly problematic in suicide research. The need for greater phenotypic refinement of suicide-related behaviors, development of and adherence to a shared suicide nomenclature, and conservative interpretation of investigational results that are limited to the precise population and suicide-related behavior under examination are discussed. PMID- 21034211 TI - Alcohol involvement in hospital-admitted nonfatal suicide acts. AB - We analyzed alcohol involvement in 84,005 medically identified live discharges for self-inflicted intentional injuries (typically suicide acts) from hospitals in 20 U.S. states in 1997. Alcohol was involved in 27% of the discharges. Evidence of alcohol was significantly more prevalent in men than women, but generally men drink more than women. Blacks had the highest alcohol involvement in their suicide acts relative to their drinking patterns. Overall, alcohol involvement rose and subsequently fell with age, with involvement above 30% for ages 30-55. Lowering the minimum legal drinking age to 18 from 21 could potentially raise alcohol-involved suicide hospitalizations among youth by an estimated 27%. PMID- 21034213 TI - Does a gatekeeper suicide prevention program work in a school setting? Evaluating training outcome and moderators of effectiveness. AB - The suicide prevention gatekeeper training program QPR (Question, Persuade, and Refer) was evaluated among school personnel using a nonequivalent control group design. Substantial gains were demonstrated from pre- to post-test for attitudes, knowledge, and beliefs regarding suicide and suicide prevention. Exploratory analyses revealed the possible moderating effects of age, professional role, prior training, and recent contact with suicidal youth on QPR participants' general knowledge, questioning, attitudes toward suicide and suicide prevention, QPR quiz scores, and self-efficacy. The need for replication using a more rigorous experimental design in the context of strong community collaboration is discussed. PMID- 21034214 TI - A conversation with Edwin Shneidman. AB - This article is a transcript of a conversation that took place with Edwin Shneidman, PhD, on August 19, 2008. Recent advances in machine learning, particularly neurocognitive computing, have provided a fresh approach to the idea of using computers to analyze the language of the suicidal person. Here this notion and many others are discussed. PMID- 21034215 TI - Suicide coverage in U.S. newspapers following the publication of the media guidelines. AB - A nationally representative sample of 968 local and national newspapers was examined to determine whether the 2001 U.S. media guidelines were followed in articles published in 2002-2003, and featuring individual cases of suicidal behavior (N = 157). We found that, during this period of time, U.S. newspaper suicide coverage did not consistently reflect the influence of the media guidelines. On the positive side, only 19% of stories included inappropriate imagery. On the negative side, suicide stories often detailed suicide method (56% of stories) and location (58%), and rarely provided information about warning signs and risk factors (1%), the roles of depression (4%) and alcohol (2%), and prevention resources (6%). Our findings, together with previous evidence, suggest the need for sustained dialogue with the media about suicide reporting. PMID- 21034216 TI - Therapeutic approaches for women predisposed to breast cancer. AB - The medical management of women at an increased risk of breast cancer has substantially changed over the past few years, with improvements in screening, cancer prevention, and treatment, and is best defined for women with mutations in BRCA1 and BRCA2. Screening techniques, such as breast magnetic resonance imaging, enable early detection of cancers in high-risk women. Prophylactic salpingo oophorectomy has been demonstrated to decrease the risk of breast and ovarian cancers, as well as mortality in BRCA1/2 mutation carriers. Most recently, there have been considerable strides in the treatment of cancers in BRCA1/2 mutation carriers. Breast cancer patients with BRCA1/2 mutations treated with systemic therapy do not appear to have excess toxicity, and have similar relapse-free and overall survival compared to noncarriers. Preclinical and early clinical research suggests that specific classes of chemotherapy may be more effective in mutation carriers. PARP inhibitors represent a novel therapeutic strategy that exploits the weaknesses of BRCA1/2-associated malignancies. PMID- 21034218 TI - Coarse-grained (multiscale) simulations in studies of biophysical and chemical systems. AB - Recent years have witnessed an explosion in computational power, leading to attempts to model ever more complex systems. Nevertheless, there remain cases for which the use of brute-force computer simulations is clearly not the solution. In such cases, great benefit can be obtained from the use of physically sound simplifications. The introduction of such coarse graining can be traced back to the early usage of a simplified model in studies of proteins. Since then, the field has progressed tremendously. In this review, we cover both key developments in the field and potential future directions. Additionally, particular emphasis is given to two general approaches, namely the renormalization and reference potential approaches, which allow one to move back and forth between the coarse grained (CG) and full models, as these approaches provide the foundation for CG modeling of complex systems. PMID- 21034219 TI - LEA proteins during water stress: not just for plants anymore. AB - Late embryogenesis abundant (LEA) proteins are extremely hydrophilic proteins that were first identified in land plants. Intracellular accumulation is tightly correlated with acquisition of desiccation tolerance, and data support their capacity to stabilize other proteins and membranes during drying, especially in the presence of sugars like trehalose. Exciting reports now show that LEA proteins are not restricted to plants; multiple forms are expressed in desiccation-tolerant animals from at least four phyla. We evaluate here the expression, subcellular localization, biochemical properties, and potential functions of LEA proteins in animal species during water stress. LEA proteins are intrinsically unstructured in aqueous solution, but surprisingly, many assume their native conformation during drying. They are targeted to multiple cellular locations, including mitochondria, and evidence supports that LEA proteins stabilize vitrified sugar glasses thought to be important in the dried state. More in vivo experimentation will be necessary to fully unravel the multiple functional properties of these macromolecules during water stress. PMID- 21034217 TI - Orexin receptors: pharmacology and therapeutic opportunities. AB - Orexin-A and -B (also known as hypocretin-1 and -2) are neuropeptides produced in the lateral hypothalamus that promote many aspects of arousal through the OX1 and OX2 receptors. In fact, they are necessary for normal wakefulness, as loss of the orexin-producing neurons causes narcolepsy in humans and rodents. This has generated considerable interest in developing small-molecule orexin receptor antagonists as a novel therapy for the treatment of insomnia. Orexin antagonists, especially those that block OX2 or both OX1 and OX2 receptors, clearly promote sleep in animals, and clinical results are encouraging: Several compounds are in Phase III trials. As the orexin system mainly promotes arousal, these new compounds will likely improve insomnia without incurring many of the side effects encountered with current medications. PMID- 21034220 TI - Venous valvular stasis-associated hypoxia and thrombosis: what is the link? AB - This review focuses on the role of the venous valves in the genesis of thrombus formation in venous thromboembolic disease (VTE). Clinical VTE and the evidence for the valvular origin of venous thrombosis are reviewed. Virchow's triad is then used as a framework for discussion to approach the question posed regarding the link between venous valvular stasis-associated hypoxia and thrombosis. Thus, the effects of blood flow stasis, hypercoagulability of blood, and the characteristics of the vessel wall within the venous valvular sinus are assessed in turn. PMID- 21034221 TI - Parkinson's disease: genetics and pathogenesis. AB - Recent investigation into the mechanisms of Parkinson's disease (PD) has generated remarkable insight while simultaneously challenging traditional conceptual frameworks. Although the disease remains defined clinically by its cardinal motor manifestations and pathologically by midbrain dopaminergic cell loss in association with Lewy bodies, it is now recognized that PD has substantially more widespread impact, causing a host of nonmotor symptoms and associated pathology in multiple regions throughout the nervous system. Further, the discovery and validation of PD-susceptibility genes contradict the historical view that environmental factors predominate, and blur distinctions between familial and sporadic disease. Genetic advances have also promoted the development of improved animal models, highlighted responsible molecular pathways, and revealed mechanistic overlap with other neurodegenerative disorders. In this review, we synthesize emerging lessons on PD pathogenesis from clinical, pathological, and genetic studies toward a unified concept of the disorder that may accelerate the design and testing of the next generation of PD therapies. PMID- 21034222 TI - Pathogenic mechanisms of HIV disease. AB - Human immunodeficiency virus (HIV) infection is generally characterized by inefficient viral transmission; an acute phase of intense viral replication and dissemination to lymphoid tissues; a chronic, often asymptomatic phase of sustained immune activation and viral replication; and an advanced phase of marked depletion of CD4(+) T cells that leads to acquired immune deficiency syndrome. Major insight into HIV transmission and each phase of infection has been gained from studies on blood and tissue specimens obtained from HIV-infected individuals, as well as from animal and ex vivo models. Not only has the introduction of effective antiretroviral therapy greatly diminished the morbidity and mortality associated with HIV disease progression, it has also provided new avenues of research toward delineating the mechanisms of HIV-induced pathogenesis. Further advances in therapeutics and informative technologies, combined with a better understanding of the immunologic and virologic components of HIV disease, hold promise for new preventative and even curative strategies. PMID- 21034224 TI - Influence of race and age on aqueous humor levels of transforming growth factor beta 2 in glaucomatous and nonglaucomatous eyes. AB - PURPOSE: To evaluate the influence of race and age on aqueous humor levels of transforming growth factor-beta 2 (TGF-beta2). METHODS: Patients >40 years of age and undergoing cataract or glaucoma surgery without associated significant intraocular pathology were selected for this study. In bilateral cases, only the first operated eye was included for evaluation. At the time of surgery, a small amount of aqueous was withdrawn. The concentration of total TGF-beta2 was measured by enzyme-linked immunosorbent assay in duplicate by a masked observer. RESULTS: Fifty-five aqueous humor samples were analyzed from subjects with an average age of 68.05 +/- 10.94 years. Overall median TGF-beta2 concentration was 247.03 pg/mL. The median concentration of TGF-beta2 was higher in eyes with glaucoma than in eyes without glaucoma (269.39 vs. 165.56 pg/mL, respectively; P = 0.001). Subgroup analysis found no significant difference between African American and Caucasian American subjects in the nonglaucomatous or glaucomatous subgroups. Age showed positive correlation with TGF-beta2 in nonglaucomatous eyes (r(2) = 0.44, P = 0.019). No correlation between age and TGF-beta2 was noted in the glaucoma group (r(2) = 0.02, P = 0.343). CONCLUSION: The aqueous humor concentration of TGF-beta2 was significantly higher in eyes with glaucoma than in eyes without glaucoma. No significant difference between the aqueous humor levels of TGF-beta2 from African American and Caucasian American subjects could be measured. However, a significant and positive correlation between age and aqueous humor concentration of TGF-beta2 in the eyes of nonglaucomatous subjects was measured. These results are consistent with the idea that elevated levels of TGF beta2 within the anterior segment contribute to the development of glaucoma. In addition, the increased risk for developing glaucoma as one ages may in part be related to the rise of this cytokine. PMID- 21034223 TI - Alternative macrophage activation and metabolism. AB - Obesity and its attendant metabolic disorders represent the great public health challenge of our time. Recent evidence suggests that onset of inflammation in metabolic tissues pathogenically links obesity to insulin resistance and type 2 diabetes. In this review, we briefly summarize the extant literature, paying special attention to the central role of the tissue-associated macrophage in the initiation of metabolic inflammation. We argue that rather than representing simple inflammatory disease, obesity and metabolic syndrome represent derangements in macrophage activation with concomitant loss of metabolic coordination. As such, the sequelae of obesity are as much products of the loss of positive macrophage influences as they are of the presence of deleterious inflammation. The therapeutic implications of this conclusion are profound because they suggest that pharmacologic targeting of macrophage activation, rather than simply inflammation, might be efficacious in treating this global epidemic. PMID- 21034225 TI - Molecular characterization and antibiotic susceptibility of Staphylococcus aureus from a multidisciplinary hospital in Romania. AB - From 2004 to 2005, 60%-72% of invasive Staphylococcus aureus isolates from Romanian hospitals were resistant to methicillin (methicillin-resistant S. aureus [MRSA]), the highest frequency for any European nation. Few reports, however, have addressed the molecular characteristics of S. aureus in Romania. In this study, we utilized spa typing, multilocus sequence typing, staphylococcal cassette chromosome mec (SCCmec) typing, dru typing, pulsed-field gel electrophoresis, and detection of virulence factors to characterize 146 S. aureus strains isolated from 2004 to 2005 at the Clinic County Hospital in Brasov. Antibiotic susceptibility patterns for all MRSA isolates and patient demographic data were also obtained. Fifty-six strains (38.4%) were determined to be MRSA by susceptibility testing and SCCmec typing. All MRSA strains were resistant to beta lactams and tetracycline, but susceptible to nitrofurans, vancomycin, and clindamycin, with inducible clindamycin resistance in 23/28 clindamycin sensitive/erythromycin-resistant isolates. Molecular typing identified 15 clonal backgrounds (CC 1, 5, 8, 8/239, 9, 15, 20, 22, 25, 30, 45, 80, 97, 101, and 121), only 4 of which were associated with MRSA (CC 1, 8/239, 30, and 80). Spa types 35 (t127, CC 1) and 351 (t030, CC 8/239) accounted for 27.4% and 21.9% of all S. aureus strains, respectively, and 19.6% and 57.1% of all MRSA strains. Both hospital-associated (SCCmec type III) and community-associated (SCCmec type IV) elements were identified within MRSA strains, whereas Panton-Valentine leukocidin was detected in 10 MRSA and 12 methicillin-sensitive S. aureus strains. These results demonstrate the presence of various endemic S. aureus clones within the Clinic County Hospital in Brasov, suggestive of ongoing nosocomial and community transmission. PMID- 21034226 TI - Nanomechanics to drive stem cells in injured tissues: insights from current research and future perspectives. AB - Stem cells reside within tissue, ensuring its natural ability to repair an injury. They are involved in the natural repair of damaged tissue, which encompasses a complex process requiring the modulation of cell survival, extracellular matrix turnover, angiogenesis, and reverse remodeling. To date, the real reparative potential of each tissue is underestimated and noncommittal. The assessment of the biophysical properties of the extracellular environment is an innovative approach to better understand mechanisms underlying stem cell function, and consequently to develop safe and effective therapeutic strategies replacing the loss of tissue. Recent studies have focused on the role played by biomechanical signals that drive stem cell death, differentiation, and paracrinicity in a genetic and/or an epigenetic manner. Mechanical stimuli acting on the shape can influence the biochemistry and gene expression of resident stem cells and, therefore, the magnitude of biological responses that promote the healing of injured tissue. Nanotechnologies have proven to be a revolutionary tool capable of dissecting the cellular mechanosensing apparatus, allowing the intercellular cross-talk to be decoded and enabling the reparative potential of tissue to be enhanced without manipulation of stem cells. This review highlights the most relevant findings of stem cell mechanobiology and presents a fascinating perspective in regenerative medicine. PMID- 21034227 TI - Higher urine volume results in additional renal iodine loss. AB - BACKGROUND: For some endocrine and nutritional biomarkers, for example, cortisol and vitamin B(12), significant associations between 24-hour renal analyte excretion and the respective 24-hour urine volume (U-Vol) have been reported. Therefore, our objective was to investigate whether 24-hour U-Vol (a marker of fluid intake) is also a relevant influencing factor of absolute daily iodine excretion. METHODS: Urinary iodine excretion rates were measured in repeatedly collected 24-hour urine samples of (i) 9 healthy women participating in a controlled diet experiment with constant iodine intake and (ii) 204 healthy free living adolescents (aged 13-18 years) who performed the respective urine collection during 2003-2008. Associations between U-Vol (L) and renal iodine excretion (MUg/24 h) were investigated cross sectionally (multiple linear regression model, PROC GLM) and longitudinally (repeated-measures regression models, PROC MIXED). The major iodine sources in the adolescent's diet (iodized salt, milk, fish, eggs, and meat) were controlled for. RESULTS: Urinary iodine excretion was significantly associated with 24-hour U-Vol in all performed fully adjusted regression models. A 1-L increase of U-Vol predicted an additional 15.0 MUg/day (adolescents, 95% confidence interval: [9.8, 20.0], p < 0.0001) and 16.5 MUg/day (women, 95% confidence interval: [9.2, 23.7], p = 0.0002) increase in iodine excretion. The longitudinal analysis in adolescents revealed a stronger relation of iodine excretion with U-Vol in girls than in boys (beta = 17.1 vs. beta = 10.5). CONCLUSION: A high fluid consumption, and thus a high U-Vol, could lead to an additional renal iodine loss that obviously cannot be compensated by the iodine contents of non-milk-based beverages, reported to amount to ~4 MUg/L, on average. For specific research questions using the biomarker 24-hour urinary iodine excretion, U-Vol should therefore be considered as a potential confounder. PMID- 21034230 TI - Salmonella enterica and Escherichia coli harboring blaCMY in retail beef and pork products. AB - We estimated the proportion of retail beef and pork products containing bla(CMY) mediated third-generation cephalosporin resistance in commensal Escherichia coli and Salmonella enterica. Samples were obtained from 50 grocery stores located in two U.S. states. From each store, 20 fresh meat products were purchased, including 7 packages of ground beef, 3 packages of beef steak, 6 packages of pork chops, and 4 packages of pork ribs. The resulting 1000 packages of fresh meat product were individually screened for the presence of E. coli or Salmonella harboring bla(CMY). Over 8% of all retail meat packages contained E. coli with bla(CMY), whereas 4% contained Salmonella and only 0.5% contained Salmonella with bla(CMY). Retail pork products more frequently yielded E. coli with bla(CMY) than did beef products (12.2% vs. 4.0%; p = 0.06). Salmonella were also recovered more frequently from pork than beef (5.8% vs. 2.4%; p < 0.01). In addition, all five Salmonella isolates with bla(CMY) were recovered from pork products. Our data suggest that enteric bacteria carrying bla(CMY) are frequently present in fresh retail meat products. However, we did not quantify the number of resistant bacteria present in these products, which makes the public health implications of this result unclear. PMID- 21034228 TI - Estimating risk of recurrence in differentiated thyroid cancer after total thyroidectomy and radioactive iodine remnant ablation: using response to therapy variables to modify the initial risk estimates predicted by the new American Thyroid Association staging system. AB - BACKGROUND: A risk-adapted approach to management of thyroid cancer requires risk estimates that change over time based on response to therapy and the course of the disease. The objective of this study was to validate the American Thyroid Association (ATA) risk of recurrence staging system and determine if an assessment of response to therapy during the first 2 years of follow-up can modify these initial risk estimates. METHODS: This retrospective review identified 588 adult follicular cell-derived thyroid cancer patients followed for a median of 7 years (range 1-15 years) after total thyroidectomy and radioactive iodine remnant ablation. Patients were stratified according to ATA risk categories (low, intermediate, or high) as part of initial staging. Clinical data obtained during the first 2 years of follow-up (suppressed thyroglobulin [Tg], stimulated Tg, and imaging studies) were used to re-stage each patient based on response to initial therapy (excellent, acceptable, or incomplete). Clinical outcomes predicted by initial ATA risk categories were compared with revised risk estimates obtained after response to therapy variables were used to modify the initial ATA risk estimates. RESULTS: Persistent structural disease or recurrence was identified in 3% of the low-risk, 21% of the intermediate-risk, and 68% of the high-risk patients (p < 0.001). Re-stratification during the first 2 years of follow-up reduced the likelihood of finding persistent structural disease or recurrence to 2% in low-risk, 2% in intermediate-risk, and 14% in high-risk patients, demonstrating an excellent response to therapy (stimulated Tg < 1 ng/mL without structural evidence of disease). Conversely, an incomplete response to initial therapy (suppressed Tg > 1 ng/mL, stimulated Tg > 10 ng/mL, rising Tg values, or structural disease identification within the first 2 years of follow up) increased the likelihood of persistent structural disease or recurrence to 13% in low-risk, 41% in intermediate-risk, and 79% in high-risk patients. CONCLUSIONS: Our data confirm that the newly proposed ATA recurrence staging system effectively predicts the risk of recurrence and persistent disease. Further, these initial ATA risk estimates can be significantly refined based on the assessment of response to initial therapy, thereby providing a dynamic risk assessment that can be used to more effectively tailor ongoing follow-up recommendations. PMID- 21034231 TI - Reviews on trichinellosis (I): renal involvement. AB - Besides cardiac and neurological complications of trichinellosis, renal involvement is the most important as regards the cases published and discussed in literature and is generally characteristic of the severe forms of the disease. This article focuses exclusively on the renal disturbances that may occur in this parasitic illness and includes a synopsis of published cases. Our primary goal was to increase the awareness of infectious diseases specialists, nephrologists, and general practitioners about these complications with possible fatal outcome. To our knowledge, this is the first international review dedicated to this topic. Cases for which enough details were available have been analyzed, and the results indicated that the mean age of the affected patients was 31.6 years, with a slightly male predominance (56.2%). The fatality rate was 26.1%. Proteinuria was detected in 84.8% of cases, hematuria in 30.4%, and casts were observed in urine specimens from 23.9% of patients. Renal failure was evidenced in 8.7% of patients, whereas renal lesions were found by biopsy or necropsy in 43.5% of cases. Of the routine laboratory parameters that are relevant for trichinellosis, mean eosinophil count was 32.2% and mean leukocyte count was 17,312 cells/MUL. Finally, we emphasize on the necessity of establishing an early and correct diagnosis of trichinellosis to avoid later and severe complications. Additionally, implementation of public health and food safety prophylactic measures against the disease must represent an immediate priority for the affected regions. PMID- 21034232 TI - Direct versus video laryngoscopic intubation by novice prehospital intubators with and without chest compressions: A pilot manikin study. AB - OBJECTIVES: To evaluate whether chest compressions affect the time taken for intubation (TTI) using the Macintosh laryngoscope and two portable video laryngoscopes (VLs) (GlideScope Ranger and Airway Scope) when used by novice prehospital caregivers, and to compare the TTIs and rates of successful intubation among the three laryngoscopes with and without chest compressions in a manikin model. METHODS: This was a pilot randomized crossover study. Twenty paramedic students and paramedics who had no clinical experience with tracheal intubation and had never used any of two VLs participated in the study. After a one-hour training session for the VLs, participants performed intubations on a Laerdal Resusci Anne Simulator placed on the floor. Each paramedic used all three laryngoscopes, with the order of usage being randomly assigned. The TTIs and rates of successful intubation among the three laryngoscopes, with and without ongoing chest compressions, were compared. RESULTS: The difference between the TTIs using each laryngoscope with and without chest compressions was not significant (Macintosh: 2.99 sec, p = 0.06; GlideScope Ranger: 2.04 sec, p = 0.11; and Airway Scope: 0.91 sec, p = 0.10). The median TTI using the Airway Scope (15.46 sec) was significantly shorter than those for the Macintosh (24.14 sec) and the GlideScope Ranger (24.12 sec) during chest compressions (p = 0.028 and p = 0.004, respectively). There were no significant differences in the rates of successful intubation among the three laryngoscopes on each condition (without chest compressions, p = 0.15; with chest compressions, p = 0.27), but the cumulative success rates related to the TTI were significantly greater with the Airway Scope than with the other devices in both conditions. CONCLUSION: In this pilot study, chest compressions did not significantly affect the TTI using the Macintosh laryngoscope and two portable VLs when used by novice prehospital caregivers in the manikin model on the floor. Considering the fairly short training time, two portable VLs may be potentially useful adjuncts for tracheal intubation during chest compressions for novice prehospital caregivers. Further studies are required to validate whether these findings are clinically relevant. PMID- 21034233 TI - Communication errors in dispatch of air medical transport. AB - BACKGROUND: Communication errors are a source of preventable medical errors. In high-risk health care settings, identifying the source and addressing root causes can reduce error and improve patient safety. While air medical transport is a high-risk setting, its sources and rates of error have been investigated only within the last several years. OBJECTIVES: This investigation examined the rate and types of communication errors during call booking of interfacility air medical transports. The primary objective was to determine the incidence and type of errors when the initial requests for transfer took place between the sending facility and transport medicine communication center. The secondary objective was to identify potential underlying causes of these errors. METHODS: Requests for urgent and emergent interfacility air medical transfers were examined prospectively during a consecutive two-week period. As the first step in call booking, sending facility staff speak directly to communication center staff and are asked for administrative, demographic, and medical details to determine patient acuity and call priority. After this information was captured, investigators contacted the sending facility to verify the information and identify any communication errors. Errors were classified as major (potentially impacting care) or minor (unlikely to impact care) and as errors of omission or commission. Common error types were presented to a management focus group to identify potential contributing causes for these errors. RESULTS: One hundred twelve calls were randomly selected during the study period, with 98 meeting study criteria. Of those, 41 (42%) calls contained a total of 65 errors. Eleven were classified as major, including five errors of omission and six errors of commission. The most common major errors were recording "no drug allergies" when a drug allergy was present (n = 4), incorrect diagnosis (n = 2), and failure to record that patients were intubated or required mechanical ventilation (n = 2 each). There were 54 minor errors, including 41 omission errors and 13 commission errors. Nearly half the errors were attributed to procedures and software. No identified error resulted in patient harm or an adverse outcome. CONCLUSIONS: Communication-based errors are common in the initial phases of call booking in air medical transport. Human and process-driven errors contribute equally to these errors. PMID- 21034234 TI - A procedure for monitoring the presence of the virulence plasmid (pYV) in Yersinia pestis under culture conditions. AB - The pathogenicity of Yersinia pestis depends on the presence of a virulence plasmid (pYV). The unstable nature of pYV in Y. pestis leads to the eventual outgrowth of pYV-less cells due to its higher growth rate. Thus, it was necessary to develop procedures to monitor the presence of the plasmid during cultivation, storage, and laboratory manipulations. A procedure was developed to monitor the presence of pYV in Y. pestis by using low calcium response and Congo red binding techniques. The selection of pYV in the isolated clones was confirmed by polymerase chain reaction and by expression of pYV-associated phenotypes. Thus, using this procedure, low calcium response-Congo red-positive clones can be isolated for use in the development of growth models of virulent Y. pestis in food. PMID- 21034235 TI - Inactivation of human and murine norovirus by high-pressure processing. AB - The effect of high hydrostatic pressure (HPP) was evaluated for inactivation of murine norovirus (MNV), a propagable norovirus (NoV), and human NoV genogroup II.4. Inactivation of MNV was assessed by viral culturing (50% tissue culture infectious dose [TCID(50)]) and real-time reverse-transcription-polymerase chain reaction (RT-qPCR), whereas NoV survival was determined only by RT-qPCR. A treatment of 450 MPa for 15 min at 45 degrees C was sufficient to inactivate 6.5 log(10) of infectious MNV in culture medium as determined by TCID(50). Further, the inactivation of MNV was enhanced when pressure was applied at an initial temperature of 25 degrees C. On the other hand, a baroprotective effect was observed when MNV suspensions were supplemented with 10 mM of CaCl(2). A 400 MPa treatment at 45 degrees C inactivated >5 log(10) of infectious MNV, whereas the addition of CaCl(2) increased the pressure resistance of MNV, with <0.5 log(10) reduction observed. MNV decay as determined by TCID(50) was generally greater than that determined by RT-qPCR; for instance, MNV genomes were detected even after 15 min treatment at 450 MPa, with <0.5 log(10) reduction. Experiments with NoV suspensions showed that all tested HPP treatments reduced the numbers of NoV by <0.5 log(10) units as determined by RT-qPCR. Additionally, RNA of human NoV was more resistant to certain HPP treatments than the RNA of MNV. PMID- 21034236 TI - Antibiotic resistance and molecular characterization of probiotic and clinical Lactobacillus strains in relation to safety aspects of probiotics. AB - The evaluation of the safety of probiotic strains includes the exclusion of antibiotic resistance of clinical importance. Ninety-two strains from the genus Lactobacillus isolated from probiotics, food, and clinical sources were included in the investigation. Species tested were the L. acidophilus group, L. casei group, L. reuteri/fermentum group, and L. sakei/curvatus group. Cell and colony morphology, fermentation patterns, and growth characteristics as well as soluble whole cell proteins were analyzed. Antibiotic resistance against clinically important agents was determined by broth dilution tests. The vanA and tet genes were confirmed. Resistances occurred mainly against gentamicin, ciprofloxacin, clindamycin, sulfonamides, and, in some cases, glycopeptides. The natural glycopeptide resistance within the L. casei group and L. reuteri appears to be not of clinical relevance, as there was no vanA gene present. Therefore, the transfer of this resistance is very unlikely. Tet-(A), -(B), -(C), -(M), or -(O) gene could not be detected. The protein fingerprinting within the L. casei group proved that L. rhamnosus strains of clinical origin clustered together with probiotic strains. For safety evaluations resistance patterns of a broad range of strains are a useful criterion together with the exclusion of known resistance genes (like the vanA gene) and can be used for decision making on the safety of probiotics, both by authorization bodies and manufacturers. PMID- 21034237 TI - The feasibility of a community-based mobile telehealth screening service for Aboriginal and Torres Strait Islander children in Australia. AB - OBJECTIVE: The increasing prevalence and earlier onset of chronic health conditions amongst Aboriginal and Torres Strait Islander people has become a concerning and significant problem. Telehealth may be a useful application for the early detection, monitoring, and treatment of chronic diseases such as ear disease and vision impairment. This study evaluates whether it is feasible to integrate a mobile telemedicine-enabled ear and eye-screening service with existing community-based services for Australian indigenous children. MATERIALS AND METHODS: A collaborative service was established with the local community and delivered from a van fitted with screening equipment and telemedicine capabilities. Indigenous children (0-16 years) were assessed at school by an aboriginal health worker for conditions impacting hearing and vision. Screening data and video-otoscopic images were uploaded to a database and made accessible to specialists via a secure Web site. Those children who failed an ear-screening assessment, tele-otology clinics were conducted remotely by an ear, nose, and throat specialist, who reviewed cases and provided a diagnosis and treatment plan. Similarly, children who failed vision assessments were referred to an optometrist for follow-up care. RESULTS: During the first 6 months, the service visited 12 of the 16 schools in the region, screening 442 of the 760 consented children (58%). Of the 183 (41%) children who failed ear screening, 59 were reviewed remotely by an ear, nose, and throat surgeon, with 9 children booked for surgery. Three hundred and four or 41% of the consenting children completed an eye assessment, in which 46 (15%) failed and required referral to the optometrist. CONCLUSIONS: It is feasible to integrate a mobile telehealth screening service with existing community-based services to provide specialist review and treatment planning at a distance. Community consultation, engagement, and collaboration in all areas of the project have been important. PMID- 21034238 TI - The impact of a telehealth web-based solution on neurosurgery triage and consultation. AB - INTRODUCTION: To enhance the quality of neurosurgery consultations, triage, and transport decisions between a Level I trauma service neurosurgery program at the University of New Mexico Hospital and referring hospitals, a secure Health Insurance Portability and Accountability Act (HIPAA)-compliant Web-based system was developed, to which digital neurological images could be sent for review by a neurosurgeon for consultation or patient transfer. Based upon prior experience of neurosurgery, it was predicted that 25% of transfer requests would be avoided if the neurosurgeons reviewed the computerized tomography scans at the time of a transfer request. In addition, it was predicted in 25% of the case that changes in management recommendations would take place independent of the transfer decision. METHODS: The program was designed to allow referring hospitals to transmit digital images to the Web site, providing consulting doctors with additional patient information. This project analyzed the neurosurgeons' responses to questions designed to determine if transport or management decisions were altered when using this telehealth program in response to a request for consultation or transfer from a rural facility. RESULTS: Analysis of the responses of the consulting neurosurgeons revealed that, after viewing the images, 44% of the potential transfers were avoided and 44% of consulted cases resulted in management recommendation changes independent of the transfer decision. CONCLUSIONS: Use of the system resulted in improved triage and changes in transfer or management recommendations. A significant number of potential transfers were avoided, resulting in transport cost avoidance, more effective use of resources, and more appropriate use of the neurosurgery service as well as improved patient preparation. PMID- 21034239 TI - VISYTER: versatile and integrated system for telerehabilitation. AB - The versatile and integrated system for telerehabilitation (VISYTER) is a software platform for developing various telerehabilitation applications. VISYTER has been designed to take into account the environments and requirements of rehabilitation services. The requirements considered in the platform design include minimal equipment beyond what is available in many rehabilitation settings, minimal maintenance, and ease of setup and operation. In addition, the platform has been designed to be able to adjust to different bandwidths, ranging from the very fast new generation of Internet to residential broadband connections. VISYTER is a secure integrated system that combines high-quality videoconferencing with access to electronic health records and other key tools in telerehabilitation such as stimuli presentation, remote multiple camera control, remote control of the display screen, and an eye contact teleprompter. The software platform is suitable for supporting low-volume services to homes, yet scalable to support high-volume enterprise-wide telehealth services. The VISYTER system has been used to develop a number of telerehabilitation applications, including a remote wheelchair prescription, adult autistic assessments, and international physical therapy teleconsultations. An evaluation of VISYTER for delivering a remote wheelchair prescription was conducted on 48 participants. Results of the evaluation indicate a high level of satisfaction from patients with the use of VISYTER. The versatility and cost-effectiveness of the platform has the potential for a wide range of telerehabilitation applications and potentially may lower the technical and economic barriers of telemedicine adoption. PMID- 21034240 TI - The correlation between breastfeeding and maternal quality of life in southern Brazil. AB - PURPOSE: This study examined the relationship between the breastfeeding efficacy and quality of life (QoL) in a sample of 89 mothers from southern Brazil. To the authors' knowledge, this is the first study to explore correlations between maternal QoL and breastfeeding efficacy in Brazil. METHODS: Research participants completed the Portuguese version of the World Health Organization Quality of Life BREF and Multicultural Quality of Life Index questionnaires. Breastfeeding efficacy was evaluated through the Breastfeeding Self-Efficacy Scale-Short Form (BSES-SF). Correlations between the scores of the QoL instruments and the BSES-SF were examined using Pearson product-moment correlation coefficients. RESULTS: There were significant correlations among the scores of the two QoL questionnaires and the BSES-SF. Multiple regression analysis revealed that both QoL instruments significantly predicted BSES-SF scores. Neither socioeconomic status nor level of educational attainment was a significant predictor of breastfeeding efficacy. CONCLUSIONS: The results from the present study indicate that breastfeeding efficacy is significantly related to QoL among mothers in southern Brazil. The association between QoL and breastfeeding efficacy appears to be independent from any effect of socioeconomic status or level of educational achievement. PMID- 21034241 TI - Maternal supplementation for prevention and treatment of vitamin D deficiency in exclusively breastfed infants. AB - Current research links newborn and infant vitamin D deficiency with various clinical outcomes, including rickets, failure to thrive, type 1 diabetes, and other immune-related diseases. Breastfed infants are often at a greater risk of developing deficiency due to their mothers' low vitamin D status. Human milk reflects the vitamin D status of the mother and often contains inadequate levels of 25-hydroxyvitamin D for infant nutrition. In 2008 the American Academy of Pediatrics (AAP) recommended 400 IU of vitamin D supplementation of all infants. However, research has indicated low levels of compliance of vitamin D supplementation of breastfed infants and a high incidence of vitamin D deficiency in the United States. Many breastfeeding advocates believe that the AAP's recommendations undermine breastfeeding, implying that human milk is inadequate for infant nutrition. Lactating mothers are also reluctant to add any supplements to their breastmilk. The literature review will examine the effectiveness and safety of maternal vitamin D supplementation for prevention and/or treatment of vitamin D deficiency in breastfed infants and lactating mothers. This method of prevention and intervention provides pediatric providers and certified lactation consultants with an alternative approach for education, counseling, promotion of breastfeeding, and treatment to improve maternal and infant health. PMID- 21034242 TI - Outcome of infants exposed to olanzapine during breastfeeding. AB - OBJECTIVE: This study evaluated the outcome of infants exposed to olanzapine during lactation. METHODS: A prospective, controlled observational study design was used. Mothers who contacted Beilinson Teratology Information Service regarding use of olanzapine while breastfeeding were followed by phone interview. Data on lactation, neonatal symptoms, and outcome at the age of 1-2 years were obtained. Mother-infant groups were compared. Mothers breastfeeding while taking olanzapine (n = 22) were compared to two control groups of mothers who continued to take olanzapine but did not breastfeed (n = 15) and to breastfeeding mothers using a drug known to be safe during lactation (n = 51). RESULTS: Follow-up was obtained for 37 of 70 women. Comparison of olanzapine-exposed breastfed versus control breastfed infants showed a similar duration of breastfeeding; however, early discontinuation of breastfeeding was more common in the olanzapine-exposed breastfed group (five of 22 vs. none of 51, p = 0.02). The rate of adverse outcomes in olanzapine-exposed breastfed infants did not differ from those of the control groups. Among the 30 newborns exposed in utero to olanzapine, no congenital birth defects were found. Neonatal symptoms were seen in six of 30 of olanzapine-exposed infants versus two of 51 of nonexposed infants (p < 0.05). A withdrawal syndrome was seen in three of 30 (10%) infants. CONCLUSIONS: No increase in adverse long-term outcomes in olanzapine-exposed breastfed infants were found. Our data in conjunction with previous estimates of very low drug exposure support continuation of breastfeeding in women treated with olanzapine. However, until additional long-term studies are available, infants exposed to olanzapine through breastmilk should be followed up. PMID- 21034243 TI - Client and provider perspectives of the efficiency and quality of care in the context of rapid scale-up of antiretroviral therapy. AB - Global scale-up of antiretroviral therapy (ART) has focused on clinical outcomes with little attention on its impact on existing health systems. In June-August 2008, we conducted a formative evaluation on ART scale-up and clinic operations at three clinics in Uganda to generate lessons for informing policy and larger public health care systems. Site visits and semistructured interviews with 10 ART clients and 6 providers at each clinic were used to examine efficiency of clinic operations (patient flow, staff allocation to appropriate duties, scheduling of clinic visits, record management) and quality of care (attending to both client and provider needs, and providing support for treatment adherence and retention). Clients reported long waiting times but otherwise general satisfaction with the quality of care. Providers reported good patient adherence and retention, and support mechanisms for clients. Like clients, providers mentioned long waiting times and high workload as major challenges to clinic expansion. Providers called for more human resources and stress-release mechanisms to prevent staff burnout. Both providers and clients perceive these clinics to be delivering good quality care, despite the recognition of congested clinics and long waiting times. These findings highlight the need to address clinic efficiency as well as support for providers in the context of rapid scale-up. PMID- 21034244 TI - Can intraocular lenses deliver antibiotics intracamerally? AB - PURPOSE: To determine the therapeutic concentrations of moxifloxacin achieved in an artificial anterior chamber by soaking the hydrophobic acrylic AcrySofTM SA60 (Alcon Inc.) intraocular lens (IOL) and the hydrophilic collamer AfinityTM CQ2015 (Staar Inc.) IOL in commercially available moxifloxacin 0.5% (VigamoxTM; Alcon Inc.). METHODS: Forty IOLs (20 Acrysof SA60 and 20 Afinity CQ2015) were soaked in 1 mL of commercially available moxifloxacin 0.5%: 10 of each IOL for 1 min, and another 10 of each IOL for 10 min. The IOLs were placed on absorbent pads for 10 s on each side to dry excess liquid, and then placed in vials of 10 mL balanced salt solution (BSSTM) for 30 min. Five milliliters of the balanced salt solution was removed and analyzed by high-pressure liquid chromatography to determine antibiotic levels. RESULTS: The moxifloxacin levels achieved after soaking the hydrophobic SA60 lens were 0.238 and 0.342 MUg/mL for 1 and 10-min soaks, respectively. The moxifloxacin levels achieved after soaking the hydrophilic CQ2015 lens were 0.283 and 0.717 MUg/mL for 1 and 10-min soaks, respectively. CONCLUSIONS: Both lenses were capable of delivering clinically significant antibiotic levels after a 1-min soak. Moxifloxacin concentrations reached at both 1 and 10-min soak times exceed the MIC(90) of the most common pathogens responsible for postoperative endophthalmitis. The antibiotic-soaked IOL has potential to become a clinically significant technique in the prevention of postoperative endophthalmitis. PMID- 21034246 TI - Prevalence of transmitted HIV drug resistance in Botswana: lessons learned from the HIVDR-Threshold Survey conducted among women presenting for routine antenatal care as part of the 2007 national sentinel survey. AB - The emergence and spread of transmitted drug resistance (TDR) poses a major threat to the success of the rapidly expanding antiretroviral treatment (ART) programs in resource-limited countries. The World Health Organization recommends the use of the HIV Drug Resistance Threshold Survey (HIVDR-TS) as an affordable means to monitor the presence of TDR in these settings. We report our experiences and results of the 2007 HIVDR-TS in Botswana, a country with one of the longest existing national public ART programs in Africa. The HIVDR-TS and HIV-1 incidence testing were performed in the two largest national sites as part of the 2007 antenatal Botswana Sentinel Survey. The HIVDR-TS showed no significant drug resistance mutations (TDR less than 5%) in one site. TDR prevalence, however, could not be ascertained at the second site due to low sample size. The agreement between HIVDR-TS eligibility criteria and laboratory-based methodologies (i.e., BED-CEIA and LS-EIA) in identifying recently HIV-1 infected adults was poor. Five years following the establishment of Botswana's public ART program, the prevalence of TDR remains low. The HIVDR-TS methodology has limitations for low density populations as in Botswana, where the majority of antenatal sites are too small to recruit sufficient numbers of patients. In addition, the eligibility criteria (age <25 years and parity (first pregnancy)) of the HIVDR-TS performed poorly in identifying recent HIV-1 infections in Botswana. An alternative sampling strategy should be considered for the surveillance of HIVDR in Botswana and similar geographic settings. PMID- 21034245 TI - Immunization with pneumolysin protects against both retinal and global damage caused by Streptococcus pneumoniae endophthalmitis. AB - PURPOSE: To determine whether immunization with pneumolysin (PLY) protects against pneumococcal endophthalmitis. METHODS: New Zealand white rabbits were immunized with a mutant form of PLY that retains only 1% of its cytolytic activity until serum IgG titers were >=51,200. For a negative control, rabbits were immunized with phosphate-buffered saline (mock). Each vitreous was injected with 10(2) colony-forming units of a clinical endophthalmitis isolate of Streptococcus pneumoniae. Severity of endophthalmitis was graded by slit lamp examination at 24 and 48 h postinfection (PI). Serial dilutions of vitreous were plated for bacterial colony-forming units quantitation, eyes were extracted for histology, and a whole blood survival assay was performed. RESULTS: Immunized rabbits had a significantly lower mean slit lamp examination score at 24 and 48 h PI when compared to mock immunized rabbits (P <= 0.002). There was not a significant difference in bacterial load in the vitreous at 24 or 48 h PI. Histological sections showed that retinas of mock immunized rabbits appeared to be destroyed, whereas those of PLY immunized rabbits remained largely intact. Damage spread to the aqueous humor, stroma, and conjunctiva of mock immunized rabbits by 48 h PI. Minimal damage was observed in the vitreous of PLY immunized rabbits and did not spread to other parts of the eye. Whole blood from immunized rabbits inhibited the growth of bacteria better than whole blood from mock immunized rabbits. CONCLUSION: Immunization with PLY helps protect the eye from damage caused by pneumococcal endophthalmitis. PMID- 21034247 TI - Various viral compartments in HIV-1-infected mothers contribute to in utero transmission of HIV-1. AB - Perinatal HIV transmission occurs in utero or intrapartum. The mechanisms and timing of transmission are not clearly understood. To compare the genetic sequences of the V3 envelope region of infant's plasma HIV to that of the mother's plasma, peripheral blood mononuclear cells (PBMC) and vaginal secretions, and correlate with timing of transmission. All 3 infants had a positive HIV PCR in the first days of life, thus classified as in utero infections. In the first mother-infant pair, two different variants were present in the infant, one correlating with maternal PBMC virus and highly homologous to virus from vaginal secretions and the other identical to sequences in maternal plasma. In the second pair, the infant plasma virus was similar to that of maternal PBMC. In the third pair, the cord blood and infant plasma virus were highly similar to maternal vaginal virus. The presence of more than one HIV variant from the maternal blood and from the vaginal compartment in the cord blood of infants presumably infected in utero could point to more than one episode of transmission or, alternatively, to transmission of PBMC virus. PMID- 21034248 TI - Effects of Mentha longifolia L. essential oil and nisin alone and in combination on Bacillus cereus and Bacillus subtilis in a food model and bacterial ultrastructural changes. AB - In the face of emerging new pathogens and ever-growing health-conscious customers, food preservation technology remains on the top agenda of food industry. This study was aimed at determining the effects of the essential oil of Mentha longifolia L., alone and in combination with nisin, on Bacillus cereus and Bacillus subtilis at 8 degrees C and 25 degrees C in a food model (commercial barley soup) during 15 days. The essential oil alone at 8 degrees C inhibited bacterial growth significantly compared with the control (p < 0.05). However, at 25 degrees C, none of the concentrations of the essential oil alone showed inhibitory effect on bacterial growth. At 8 degrees C, the combination effect of the essential oil and nisin on bacteria was noted at 0.25 MUg mL(-1) for nisin and 0.05 MUL mL(-1) for the essential oil (p < 0.05). The combination of nisin and the essential oil demonstrated significant inhibitory effects on the vegetative forms of bacteria at 25 degrees C, although it was comparable to that of nisin alone at the same concentrations. Electron microscopy studies revealed a great deal of damage to B. cereus treated with a combination of nisin and the essential oil. However, the combination of nisin with the essential oil led to a complete destruction of cell wall and cytoplasm of vegetative cells of B. subtilis. PMID- 21034249 TI - Evaluation of phage treatment as a strategy to reduce Salmonella populations in growing swine. AB - Salmonella is a foodborne pathogenic bacterium that causes human illnesses and morbidity and mortality in swine. Bacteriophages are viruses that prey on bacteria and are naturally found in many microbial environments, including the gut of food animals, and have been suggested as a potential intervention strategy to reduce Salmonella levels in the live animal. The present study was designed to determine if anti-Salmonella phages isolated from the feces of commercial finishing swine could reduce gastrointestinal populations of the foodborne pathogen Salmonella Typhimurium in artificially inoculated swine. Weaned pigs (n = 48) were randomly assigned to two treatment groups (control or phage-treated). Each pig was inoculated with Salmonella Typhimurium (2 * 10(10) colony forming units/pig) via oral gavage at 0 h and fecal samples were collected every 24 h. Swine were inoculated with a phage cocktail via oral gavage (3 * 10(9) plaque forming units) at 24 and 48 h. Pigs were humanely killed at 96 h, and cecal and rectal intestinal contents were collected for quantitative and qualitative analysis. Fecal Salmonella populations in phage-treated pigs were lower (p < 0.09) than controls after 48 h. Phage treatment reduced intestinal populations of inoculated Salmonella Typhimurium in pigs compared to controls at necropsy. Cecal populations were reduced (p = 0.07) by phage treatment >1.4 log(10) colony forming units/g digesta, and rectal populations were numerically reduced. The number of pigs that contained inoculated Salmonella Typhimurium was reduced by phage treatment, but a significant (p < 0.05) reduction was only observed in the rectum. We conclude that phages can be a viable tool to reduce Salmonella in swine. Further research needs to be performed to determine the most efficacious dosing regimens and the most effective combinations of phages targeting the diverse Salmonella population found in swine before they can enter the food supply. PMID- 21034250 TI - Toward standardization of carbohydrate-deficient transferrin (CDT) measurements: II. Performance of a laboratory network running the HPLC candidate reference measurement procedure and evaluation of a candidate reference material. AB - Carbohydrate-deficient transferrin (CDT) is a descriptive term used for a temporary change in the transferrin glycosylation profile caused by alcohol, and used as a biomarker of chronic high alcohol consumption. The use of an array of methods for measurement of CDT in various absolute or relative amounts, and sometimes covering different transferrin glycoforms, has complicated the comparability of results and caused confusion among medical staff. This situation prompted initiation of an IFCC Working Group on CDT standardization. This second publication of the WG-CDT covers the establishment of a network of reference laboratories running a high-performance liquid chromatography (HPLC) candidate reference measurement procedure, and evaluation of candidate secondary reference materials. The network laboratories demonstrated good and reproducible performance and thus can be used to assign target values for calibrators and controls. A candidate secondary reference material based on native human serum lyophilized with a cryo-/lyoprotectant to prevent protein denaturation was found to be commutable and stable during storage. A proposed strategy for calibration of different CDT methods is also presented. In an external quality assurance study involving 66 laboratories and covering the current routine CDT assays (HPLC, capillary electrophoresis and immunoassay), recalculation of observed results based on the nominal values for the candidate calibrator reduced the overall coefficient of variation from 18.9% to 5.5%. The logistics for distribution of reference materials and review of results were found to be functional, indicating that a full reference system for CDT may soon be available. PMID- 21034251 TI - Interlaboratory study of free monoclonal immunoglobulin light chain quantification. AB - BACKGROUND: Quantification of monoclonal immunoglobulin free light chains (FLCs) in serum is used increasingly in clinical practice for the diagnosis, prognostic assessment, and treatment monitoring of monoclonal gammopathies. It is used as an adjunct to standard serum protein electrophoresis and immunofixation. However, methods for FLC quantification need further standardization and validation. METHODS: The Czech Myeloma Group and the Czech Society of Clinical Biochemistry have initiated an interlaboratory study where six laboratories collaborating with the primary myeloma treatment centres measured FLC concentrations in 12 serum samples from patients with monoclonal gammopathies. RESULTS: Repeatability of the measurements in five laboratories was calculated based on differences between the results of duplicate measurements. We found that repeatability depended more on the laboratory than on the device used for measurement. CONCLUSIONS: The study revealed several weak points in the methodology, including the need for a uniform sample dilution procedure. Interlaboratory reproducibility was comparable with values achieved in the NEQAS programme. Because the kappa/lambda ratio cannot be measured with high precision, kappa and lambda FLC concentrations should be used where possible. Due to its impact on the clinical management of patients with gammopathy, FLC quantification needs to become a part of the regular quality control cycle in myeloma centres. PMID- 21034252 TI - Standardization activities in the field of thyroid function tests: a status report. AB - BACKGROUND: Laboratory testing is an essential tool for diagnosis and management of thyroid diseases. However, the current status of standardization hampers the interchangeability of results. To improve this situation, the Working Group for Standardization of Thyroid Function Tests was established. METHODS: Method comparisons were organized for measurement of human thyroid stimulating hormone (TSH), and free and total thyroid hormone in serum from apparently healthy donors. The aim was to assess the status of standardization and the quality of the performance of current routine assays. A second objective was to investigate the effect of mathematical recalibration of the results using their relationship to the overall mean (TSH) or the reference measurement procedure values (other thyroid hormones). RESULTS: The need for standardization was shown to be highest for free thyroid hormone and total triiodothyronine measurements, while the majority of TSH and total thyroxine assays agreed within 10% of the reference. Most assays showed good performance. However, some could benefit from improved precision, consistency of calibration, or within- and between-run stability. Recalibration eliminated assay-specific bias. Thus, the residual spread was due to within-method effects. Not withstanding, sample-related effects remained. CONCLUSIONS: These studies confirmed the feasibility of standardization based on method comparison with native sera, but highlighted the need to resolve issues, such as sample-related effects. In view of the fact that in this phase the project worked with samples from individuals with euthyroid status, the next method comparison shall place emphasis on challenging the performance of the assays with clinical samples and expanding the covered measurement range. PMID- 21034253 TI - Introduction of a new cobalamin (vitamin B12) assay: lessons from a flawed validation study. AB - BACKGROUND: Plasma vitamin B12 [cobalamin (Cbl)] concentrations are usually measured as a screening marker for vitamin B12 deficiency. Siemens Healthcare Diagnostics has introduced Cbl assays for various platforms, i.e., the immulite (IML) 2000 and 2500. In our laboratories, regular validation studies for the IML 2500 were conducted and showed acceptable quality specifications. After the introduction of the IML 2500 Cbl assay, clinicians in the department of internal medicine reported an increased frequency of patients with Cbl-concentrations less than 148 pmol/L. METHODS: In order to investigate this claim from the clinicians, we retrospectively analyzed the internal and external quality control (QC) of the Cbl assay. In addition, the monthly patient means for the Cbl assay were analyzed both before and after the introduction of the new Cbl assay. RESULTS: No abnormalities were found in the internal and external QCs. However, the monthly patient means for the Cbl assay showed a statistically significant decrease in cobalamin concentrations. Siemens acknowledged the problems and formulated a new Cbl assay, which was subsequently validated in our laboratories and showed equivocal Cbl results when compared to the IML 2000 Cbl assay. CONCLUSIONS: We report a flawed validation study conducted by the manufacturer that resulted in an undetected analytical problem in the IML 2500 Cbl assay, its subsequent introduction on the market, the final recognition of the poor performance of the assay by our clinicians, and the eventual resolution by the manufacturer. Hence, it emphasizes the utmost importance for thorough comparison between assays over the entire measurement range, even when both assays are produced by the same manufacturer. PMID- 21034254 TI - Development of an innovative serological test for detection of antibodies to Treponema pallidum. PMID- 21034255 TI - Towards the development of a certified reference material for hemoglobin A2. AB - BACKGROUND: In 2004, a working group on the standardization of hemoglobin A(2) (HbA(2)) was created within the IFCC, with the aim of developing a reference system for this analyte. One goal was to prepare a certified reference material in collaboration with the Institute for Reference Materials and Measurements (IRMM). This paper describes the properties of a first batch of this candidate study material. METHODS: Eighty millilitre of fresh whole blood, collected from a healthy blood donor, was treated by removing plasma, white blood cells and platelets. Red cells were hemolyzed to prepare 100 vials of lyophilized material (approximately 155 mg per vial). After reconstitution, the HbA(2) content was measured with a total of seven HPLC methods, three electrophoretic techniques, and two capillary electrophoresis (CE) methods. Homogeneity was tested in a subset of five vials. Stability during storage at +4 degrees C and -20 degrees C was tested monthly over a period of 1 year. The commutability of this material was assessed by analysing the study material together with a set of 54 fresh blood samples, with a subgroup of the above mentioned methods, only by one routine HPLC (Bio-Rad Variant II, dual kit) and by a CE method (Beckman PA800, Analis kit), respectively. RESULTS: The chromatographic and electrophoretic patterns obtained by all the HPLC, electrophoretic and CE techniques did not show any difference between those obtained using the first study material and those obtained with fresh blood samples. The lot was found to be homogeneous on the basis of the content of lyophilized powder per vial. The HbA(2) concentration in the lyophilized material remained stable at +4 degrees C and -20 degrees C, even after 1 year of storage. After reconstitution, the HbA(2) concentration did not change for more than 2 weeks in the refrigerator at +4 degrees C. The normalized residual of the study material, measuring the degree of its commutability was 0.9, similar to that obtained on other home prepared and some commercial controls. CONCLUSIONS: Ideally, fresh whole blood is the best reference material in the meterological traceability chain for HbA(2) analysis. However, for a number of reasons the preparation of large batches of fresh whole blood to be used as secondary reference material for HbA(2) is not practical. In our work, we have proven that lyophilization does not appear to cause any matrix effect or inhomogeneity in the study material, which also confirmed to be commutable for the Bio-Rad Variant II (dual kit) and Beckman PA800 (Analis kit) methods. We conclude that a material similarly prepared as the current study material and value assigned with the candidate reference measurement procedure still under development will be suitable to calibrate various routine methods for HbA(2). This will result in improvement of the inter-method variability for this important biochemical marker. PMID- 21034256 TI - Crystal-associated pseudoeosinophilia of synovial fluid. PMID- 21034257 TI - First certified reference material for cystatin C in human serum ERM-DA471/IFCC. AB - The IFCC Working Group for the Standardisation of Cystatin C (WG-SCC), in collaboration with the Institute for Reference Materials and Measurements (IRMM), announces the availability of the new certified reference material ERM DA471/IFCC. The material was characterised using a pure protein primary reference preparation (PRP) as calibrant. The PRP was prepared from recombinant cystatin C, and its concentration measured using dry mass determination. The characterisation of ERM-DA471/IFCC was performed by particle enhanced immuno-nephelometry, particle enhanced immuno-turbidimetry, and enzyme amplified single radial immuno diffusion. The certified cystatin C mass concentration in ERM-DA471/IFCC, if reconstituted according to the specified procedure, is 5.48 mg/L, the expanded uncertainty (k=2) being 0.15 mg/L. PMID- 21034258 TI - Genetic basis of thrombosis. AB - Venous thrombosis (VT) represents a common and serious disorder that occurs as the result of clotting of the blood in the venous system and venous obstruction. Environmental risk factors and genetic predisposition play an important role in the development of thrombosis. It is therefore seen as a classic example of a complex common disease. We have focused on the role of genetic risk factors, primarily related to the hemostatic system, in triggering thrombotic events. Since the identification of antithrombin deficiency in 1965, major efforts have been made during the past 15 years to identify other genetic entities that lead to increased thrombotic risk. Results of early genetic studies demonstrated that two types of genetic defects cause VT: loss of function mutations in the natural anticoagulants antithrombin, protein C and protein S and gain of function mutations in procoagulant factors V (FV Leiden) and II (prothrombin G20210A). The high incidence of these mutations in Caucasians induced a shift from family studies to case-control association studies. Several investigations have been performed on the role of other candidate genetic risk factors predisposing to VT, including such variants in FXIII, FIX and fibrinogen genes. Moreover, the contribution of genetic variation in genes encoding less-well studied proteins that are part of the anticoagulant pathways has been evaluated. Recently, different genome-wide association studies have been performed in which several single nucleotide polymorphisms were investigated and related to the risk of VT. However, further studies are needed to identify additional genetic causes of thrombosis and to assess functional molecular mechanisms. PMID- 21034259 TI - Low concentrations of serum n-3 polyunsaturated fatty acids in non-alcoholic fatty liver disease patients with liver injury. PMID- 21034260 TI - Common reference intervals for aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) in serum: results from an IFCC multicenter study. AB - BACKGROUND: Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) measurements are important for the assessment of liver damage. The aim of this study was to define the reference intervals (RIs) for these enzymes in adults, paying attention to standardization of the methods used and careful selection of the reference population. METHODS: AST, ALT and GGT were measured with commercial analytical systems standardized to the IFCC recommended reference measurement systems. Three centers (two in Italy and one in China) measured their own freshly collected samples; one of these centers also measured frozen samples from the Nordic Countries RI Project and from a Turkish center. RIs were generated using non-parametric techniques from the results of 765 individuals (411 females and 354 males, 18-85 years old) selected on the basis of the results of other laboratory tests and a specific questionnaire. RESULTS: AST results from the four regions (Milan, Beijing, Bursa and Nordic Countries) were statistically different, but these differences were too small to be clinically relevant. Likewise, differences between the upper reference limits for genders was only 1.7 U/L (0.03 MUkat/L), allowing a single RI of 11-34 U/L (0.18-0.57 MUkat/L) to be defined. Interregional differences were not statistically significant for ALT, but partitioning was required due to significant gender differences. RIs for ALT were 8-41 U/L (0.13-0.68 MUkat/L) for females and 9-59 U/L (0.15-0.99 MUkat/L) for males, respectively. The upper reference limits for GGT from the Nordic Country population were higher than those from the other three regions and results from this group were excluded from final calculations. The GGT RIs were 6-40 U/L (0.11-0.66 MUkat/L) for females and 12-68 U/L (0.20- 1.13 MUkat/L) for males, respectively. CONCLUSIONS: For AST and ALT, the implementation of common RIs appears to be possible, because no differences between regions were observed. However, a common RI for GGT that is applicable worldwide appears unlikely due to differences among populations. PMID- 21034261 TI - Eavesdropping by bacteria: the role of SdiA in Escherichia coli and Salmonella enterica serovar Typhimurium quorum sensing. AB - Many gram-negative bacteria utilize N-acyl-L-homoserine lactones (AHLs) to bind to transcriptional regulators leading to activation or repression of target genes. Escherichia coli and Salmonella enterica do not synthesize AHLs but do contain the AHL receptor, SdiA. Studies reveal that SdiA can bind AHLs produced by other bacterial species and thereby allow E. coli and S. enterica to regulate gene transcription. The Salmonella sdiA gene regulates the rck gene, which mediates Salmonella adhesion and invasion of epithelial cells and the resistance of the organism to complement. In E. coli, there is some evidence that SdiA may regulate genes associated with acid resistance, virulence, motility, biofilm formation, and autoinducer-2 transport and processing. However, there is a lack of information concerning the role of SdiA in regulating growth and survival of E. coli and Salmonella in food environments, and therefore studies in this area are needed. PMID- 21034262 TI - Epidemiological investigation of Salmonella enterica serovar Kedougou in Thailand. AB - OBJECTIVE: Salmonella enterica serovar Kedougou is among the top 10 serovars reported in northern Thailand. The objective of this study was to identify risk factors associated with Salmonella Kedougou infection in Thailand and to compare the molecular types and antimicrobial resistance with Salmonella Kedougou isolates of human origin from United States and of animal origin from the United Kingdom. METHODS: Data from 13,976 Salmonella infections of which 253 were Salmonella Kedougou collected in Thailand between 2002 and 2008 were analyzed by logistic regression. Antimicrobial susceptibility testing and pulsed-field gel electrophoresis (PFGE) were performed on selected Salmonella Kedougou strains causing infections in Thailand (n = 66), and compared to isolates from the United States (n = 5) and the United Kingdom (n = 20). RESULTS: Logistic analysis revealed season (hot/dry; p = 0.023), region (northern Thailand; p < 0.001), and specimen (stool; p < 0.001) as significant risk factors associated with Salmonella Kedougou infection compared to other nontyphoid Salmonella. Of the Salmonella Kedougou isolates of human origin, 84% exhibited resistance to at least three antimicrobial classes. Three strains recovered from human stool in Thailand were resistant to third-generation cephalosporins: two harbored bla(CTX M-63) and one bla(CMY-2). PFGE revealed 45 unique clusters. Isolates obtained from humans in Thailand and the United States presented identical PFGE profiles suggesting a travel association, whereas the majority of the animal isolates from United Kingdom clustered separately. CONCLUSIONS: This study reveals Salmonella Kedougou as a major cause of human infections in northern Thailand especially during the hot period and suggests a global spread probably due to travel. The clonal types causing infections in humans differed from those observed in animals in United Kingdom, which suggests the absence of an epidemiological link and could suggest differences in virulence. The high frequency of antimicrobial resistance, including emergence of resistance to fluoroquinolones and third generation cephalosporins, might pose problems for treatment of infections. PMID- 21034263 TI - Antimicrobial susceptibility of Staphylococcus aureus and characterization of methicillin-resistant Staphylococcus aureus isolated from bovine mastitis in Korea. AB - A total of 402 Staphylococcus aureus isolates from bovine mastitis milk collected during 2003-2009 in Korea were tested for susceptibility to 20 antimicrobial agents. All S. aureus isolates were susceptible to 11 of 20 antimicrobials tested; no resistance was observed against pirlimycin, telithromycin, novobiocin, penicillin/novobiocin, quinupristin/dalfopristin, clindamycin, rifampin, ciprofloxacin, trimethprim/sulfamethoxazol, vancomycin, and linezolid. Over 66% of the S. aureus isolates were resistant to penicillin. Resistance was also seen for gentamicin (11.9%), erythromycin (7.7%), methicillin (oxacillin and cefoxitin, 6.2%), and tetracycline (4.2%). No noticeable change was observed in penicillin, gentamicin, and erythromycin resistance over the 7-year period. Tetracycline resistance appeared to decrease consistently, whereas methicillin resistance was observed from 2005. About 2.7% (11/402) were resistant to three or more antimicrobials. Genotyping of the 17 methicillin-resistant S. aureus (MRSA) isolated from each cow revealed two staphylococcal cassette chromosome mec (SCCmec) types (IV and IVa), three spa types (t286, t324, and untypable), and two sequence types (ST1 and ST72). Eleven of 17 (64.7%) MRSA strains belonged to SCCmec IVa-t324-ST72. The rest of strains belonged to SCCmec IVa-t286-ST1 (n = 3) and SCCmec IV-untypable-ST72 (n = 3). None of the MRSA carried the Panton Valentine leukocidin gene. These characteristics are the same as those found in community-acquired (CA) MRSA strains prevalent in humans in Korea. Three pulsed field gel electrophoresis types (A-C) were observed among the 17 MRSA strains examined, and 14 strains belonged to the same pulsed-field gel electrophoresis pattern regardless of their geographical origin and year of isolation. The results of this study provide evidence of CA-MRSA infection in dairy cattle for the first time in Korea. PMID- 21034264 TI - Assessment of diagnostic tools for identifying cattle shedding and super-shedding Escherichia coli O157:H7 in a longitudinal study of naturally infected feedlot steers in Ohio. AB - The objectives of this study were to compare the performance of different diagnostic protocols (rectoanal mucosal swabs and immunomagnetic separation [RAMS IMS], fecal samples and IMS [fecal-IMS], and direct plating) to determine the prevalence of Escherichia coli O157:H7 and to evaluate the pattern of E. coli O157:H7 shedding and super-shedding (defined as having a direct plating count equal to or >10(4) colony forming units of E. coli O157:H7 per gram of feces) in a longitudinal study of naturally infected feedlot steers. RAMS and fecal grab samples were obtained at 14-day intervals from 168 Angus-cross beef steers over a period of 22 weeks. Fecal samples were assessed by direct plating and IMS, whereas RAMS were tested only by enrichment followed by IMS to recover E. coli O157:H7. The period prevalence for shedding was high (62%) among feedlot steers and super-shedding was higher (23%) than anticipated. Although direct plating was the least sensitive method to detect E. coli O157:H7-positive samples, over 20% of high bacterial load samples were not detected by RAMS-IMS and/or fecal-IMS. The sensitivity of RAMS-IMS, fecal-IMS, and direct plating protocols was estimated using simple and multilevel mixed-effects logistic regression models, in which the dependent variable was the dichotomous results of each test and gold standard (i.e., parallel interpretation of the three protocols)-positive individuals were included as an independent variable along with other factors such as dietary supplements, time of sampling, and being exposed to a super shedding pen-mate. The associations between these factors and the sensitivity of the diagnostic protocols were not statistically significant. In conclusion, differences in the reported impact of diet and probiotics on the shedding of E. coli O157:H7 in previous studies using RAMS-IMS or fecal-IMS were unlikely due to their impact on test performance. PMID- 21034265 TI - Characterization of toxin genes and antimicrobial susceptibility of Staphylococcus aureus isolates from Louisiana retail meats. AB - Staphylococcus aureus is a leading cause of food poisoning worldwide due to the production of heat-stable enterotoxins. Recently, the isolation of methicillin resistant S. aureus (MRSA) from food animals and retail meats raised additional food safety concerns. In this study, we characterized 152 S. aureus isolates, including 22 MRSA recovered from Louisiana retail pork and beef meats, for the prevalence of nine enterotoxin and four other exotoxin genes by polymerase chain reaction and antimicrobial susceptibility testing by broth microdilution. Overall, 85% of S. aureus isolates were positive for at least one of six enterotoxin genes identified and 66% harbored two to four enterotoxin genes. The two most predominant ones were seg and sei (66% each), followed by seh (20%), sed (15%), sej (13%), and sea (1%). No isolates harbored enterotoxin genes seb, sec, or see, the toxic shock syndrome toxin 1 gene tst, or the exfoliative toxin genes eta or etb. Three MRSA isolates were the only ones harboring Panton-Valentine leucocidin. Resistances were common to penicillin (71%), ampicillin (68%), and tetracycline (67%), followed by erythromycin (30%), clindamycin (18%), oxacillin with 2% NaCl (14%), ciprofloxacin (13%), levofloxacin (13%), gentamicin (3%), quinupristin/dapfopristin (3%), chloramphenicol (2%), and moxifloxacin (1%). Multidrug resistance was commonly observed among MRSA isolates and S. aureus isolates from pork. This study demonstrated that S. aureus isolates found in Louisiana retail pork and beef meats possessed various enterotoxin genes and antimicrobial resistance profiles. Therefore, vigilant food safety practice needs to be implemented for people who handle raw meat products to prevent foodborne infections and intoxications due to S. aureus contamination. PMID- 21034266 TI - Intracellular pH in Campylobacter jejuni when treated with aqueous chlorine dioxide. AB - The aim of this study was to investigate the response of Campylobacter jejuni at single-cell level when exposed to different concentrations of chlorine dioxide (ClO(2)). The parameter of choice, intracellular pH (pH(i)), was determined by using fluorescence ratio imaging microscopy with a pH-sensitive, ratiometric 5(6) carboxyfluorescein diacetate succinimidyl ester probe. In addition, the culturability expressed in colony counts was determined. Our results revealed that several subpopulations with different physiological states, as judged by their pH(i), were created by ClO(2) treatment. The greater the concentration of ClO(2), the smaller the subpopulation of healthy cells with pH(i) > 6.8 and the smaller the colony count as determined on nonselective agar plates. ClO(2) at concentrations (60 ppm) induced injuries that resulted in complete loss of culturability and adversely affected the ability to resuscitate under subsequent more favorable conditions. The presence of injured cells in food could present a risk for public health. Additional hurdles have to be included in food preservation to suppress the survival and recovery of injured cells. PMID- 21034267 TI - Biofilm formation by Aeromonas hydrophila on green-leafy vegetables: cabbage and lettuce. AB - Aeromonas hydrophila is the most well known of the six species of Aeromonas, which has been linked to two groups of human diseases: septicemia and gastroenteritis. Reference strain ATCC 7966 and biofilm strains TUB19, TUB20, and TUB21 were investigated for their ability to form biofilm in vitro (after 48 h on polystyrene surface) and on the surface of two green-leafy vegetables, cabbage and lettuce (after 1, 2, 4, and 24 h). Attachment strength (S(R)) of these strains to the vegetable surface was also measured in the same time intervals. The ATCC 7966 and TUB19 had high ability to form biofilm in vitro compared with TUB20 and TUB21 in full strength tryptone soy broth or under starvation conditions in diluted tryptone soy broth (1:20, v/v). Cell surface hydrophobicity of the biofilm strains was lower than that of the reference strain. The biofilm of all tested strains on polystyrene surfaces differed from that on the vegetable surfaces. All strains studied rapidly attached to both green leafy vegetables (after 1 h). S(R) and cell populations (loosely and strongly attached cells) significantly (p < 0.05) increased with contact time; however, no significant (p > 0.05) differences in cell populations were recorded after 4 and 24 h. The highest S(R) and cell population (log CFU cm-2) were recorded by TUB19. In conclusion, the use of A. hydrophila strains isolated from environmental biofilm samples may be more useful for understanding biofilm formation on green-leafy vegetables than the reference or laboratory strains. The attachment of A. hydrophila was significantly affected by the surfaces of green-leafy vegetables. Further studies are required to improve our understanding of the interaction between human microbial pathogens and surfaces of raw vegetables. PMID- 21034268 TI - Food- and waterborne disease outbreaks in Australian long-term care facilities, 2001-2008. AB - Abstract Food- or waterborne diseases in long-term care facilities (LTCF) can result in serious outcomes, including deaths, and they are potentially preventable. We analyzed data collected by OzFoodNet on food- and waterborne disease outbreaks occurring in LTCF in Australia from 2001 to 2008. We compared outbreaks by the number of persons affected, etiology, and implicated vehicle. During 8 years of surveillance, 5.9% (55/936) of all food- and waterborne outbreaks in Australia occurred in LTCF. These LTCF outbreaks affected a total of 909 people, with 66 hospitalized and 23 deaths. The annual incidence of food- or waterborne outbreaks was 1.9 (95% confidence intervals 1.0-3.7) per 1000 facilities. Salmonella caused 17 outbreaks, Clostridium perfringens 14 outbreaks, Campylobacter 8 outbreaks, and norovirus 1 outbreak. Residents were at higher risk of death during outbreaks of salmonellosis than for all other outbreaks combined (relative risk 7.8, 95% confidence intervals 1.8-33.8). Of 15 outbreaks of unknown etiology, 11 were suspected to be due to C. perfringens intoxication. Food vehicles were only identified in 27% (14/52) of outbreaks, with six outbreak investigations implicating pureed foods. Dishes containing raw eggs were implicated as the cause of four outbreaks. Three outbreaks of suspected waterborne disease were attributed to rainwater collected from facility roofs. To prevent disease outbreaks, facilities need to improve handling of pureed foods, avoid feeding residents raw or undercooked eggs, and ensure that rainwater tanks have a scheduled maintenance and disinfection program. PMID- 21034269 TI - Antibacterial activity against foodborne Staphylococcus aureus and antioxidant capacity of various pure phenolic compounds. AB - Six pure phenolic compounds (hydroquinone, thymol, carvacrol, butylated hydroxyanisole, gallic acid, and octyl gallate) were tested for their minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against several strains of Staphylococcus aureus isolated from dairy and meat products. In addition, S. aureus reference strains (American Type Culture Collection) for antimicrobial studies and/or isolated from human infections and outbreaks of food poisoning were included in the study. Of the compounds tested, octyl gallate and hydroquinone were the most effective against S. aureus (mean MIC values of 20.89 and 103.05 MUg/mL, respectively) and carvacrol and thymol the least (mean MIC values of about 413 MUg/mL). The mean MBC values were 40.84, 194.37, 417.46, and 581.90 MUg/mL for octyl gallate, hydroquinone, carvacrol, and thymol, respectively. Meat isolates were more resistant than those of dairy origin to hydroquinone, gallic acid, and octyl gallate, as well as to penicillin G (used as a control of the methodology used); gallic acid and penicillin G showed the highest differences in MIC values between the groups of strains (about 10 and 200 times, respectively). On the other hand, when we tested the isolates included in each group of strains (dairy, meat, and other/mixed sources) we only detected significant differences (p < 0.05) among dairy and isolates from other/mixed sources for hydroquinone and thymol, respectively. However, strains of meat origin exhibited significant differences among each other (p < 0.05) to most of the phenolic compounds tested (hydroquinone, carvacrol, gallic acid, and octyl gallate). The relationship between MICs and MBCs for each of the phenolic compounds tested suggested a bactericidal mechanism of action against S. aureus. Gallic acid and octyl gallate exhibited the highest antioxidant capacity and thymol and carvacrol the lowest. So, octyl gallate is an agent with both antimicrobial and antioxidant properties, which would be of interest to use in the food industry. PMID- 21034270 TI - Qualitative and quantitative detection of human pathogenic Yersinia enterocolitica in different food matrices at retail level in Bavaria. AB - Yersinia enterocolitica is a major foodborne pathogen and the third most important bacteriological cause of diarrhea in Germany. However, studies investigating the occurrence of human pathogenic Y. enterocolitica in food at the retail level are very rare. Most of the studies published so far show qualitative but not quantitative data concerning the prevalence of this human pathogen. In this study the qualitative and quantitative assessment of human pathogenic Y. enterocolitica in different food matrices was investigated. For the qualitative analysis we used an enrichment method according to the International Organisation of Standardization (ISO) standard in combination with a real-time polymerase chain reaction (PCR) method detecting the ail gene of Y. enterocolitica. After detecting Y. enterocolitica in a sample, a quantitative investigation on Cefsulodin-Irgasan-Novobiocin (CIN) Agar was done to get information about the contamination level of the different samples. During the years 2008 and 2009, 446 samples of pork and pork products, 51 samples of game meat, and 61 raw milk samples were investigated for the presence of human pathogenic Y. enterocolitica. The samples were collected at the retail level in Bavaria. From the pork samples investigated, 81 samples (18%) were positive for the ail gene by real-time PCR, but human pathogenic Y. enterocolitica O:3 were found only in 46 (10%) pork samples by culture; the concentration in the samples ranged between 0.04 cfu/g and 2.30 * 10(5) cfu/g. Three game meat samples were positive by real-time PCR, but not by the cultural detection. All raw milk samples were negative by real time PCR and culture. PMID- 21034271 TI - Effects of restricted antimicrobial exposure on antimicrobial resistance in fecal Escherichia coli from feedlot cattle. AB - OBJECTIVES: The primary objective was to evaluate differences in antimicrobial resistance among enteric bacteria recovered from feedlot cattle that were being raised without exposure to antimicrobial drugs (AMDs) and those reared using conventional practices. MATERIALS: Forty pens of feedlot cattle (4557 total animals) that were being fed without AMD exposures were selected for enrollment as were 44 pens of cattle (4913 total animals) being fed for production of conventional beef products at the same feedlots. Fecal samples were collected from the floors of pens approximately biweekly through the middle of the feeding period and again prior to slaughter. Samples were cultured to recover nontype specific Escherichia coli (NTSEC) and Salmonella enterica, and isolates were evaluated for susceptibility to a panel of AMDs. RESULTS: Cattle enrolled in the study did not differ between groups in entry weight or finish weight, but cattle with restricted AMD and hormone exposures were fed for an average of 50 days longer than conventionally reared cattle (p < 0.001). Resistance among NTSEC isolates was most common to tetracycline, streptomycin, and sulfamethoxazole, and there were slightly higher prevalence of resistance among NTSEC isolates recovered from conventionally reared cattle. Therapeutic AMD exposures did not have a detectable impact on the prevalence of resistance among NTSEC. Although there were detectable temporal trends through the feeding period for resistance to tetracycline, naladixic acid, chloramphenicol, and cephalothin, the direction of trends differed among drugs and these trends were not associated with study groups. S. enterica was recovered rarely (0.73%) but at similar prevalences from cattle with both rearing methods. CONCLUSIONS: These findings suggest that conventional feedlot production methods (including parenteral and in-feed use of AMDs) do not predictably or uniformly increase the prevalence of antimicrobial resistance among fecal NTSEC when compared with rearing methods that restrict exposure to AMDs. PMID- 21034272 TI - Relationship between components of metabolic syndrome and polysomnographic findings in obstructive sleep apnea. AB - AIMS: Obstructive sleep apnea/hypopnea syndrome (OSAHS) and metabolic syndrome are both growing health concerns, owing to the worldwide obesity epidemic. This study evaluates the potential association between the parameters of metabolic syndrome and OSAHS. METHODS: A total of 125 consecutive patients undergoing complete full night polysomnography were included. Insulin resistance (IR) was estimated using the homeostasis model assessment (HOMA), and metabolic syndrome was diagnosed according to the National Cholesterol Education Program (NCEP) criteria. RESULTS: The prevalence of metabolic syndrome was 23.8% among patients with OSAHS. We found that IR, age, weight, hypertension, and metabolic syndrome prevalence increased significantly with severity of OSAHS. There were no differences between groups for lipid panels including total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). Subjects with metabolic syndrome had significantly lowest desaturation value (76% vs. 81%) desaturation (76% vs. 81%, P = 0.003), lower mean nocturnal oxygen saturation (89.9% vs. 92.3%, P < 0.00.1), higher apnea-hypopnea index (AHI) (40.9 vs. 17, P < 0.001), and higher oxygen desaturation index (38 vs. 17, P = 0.002). Lowest desaturation and mean nocturnal oxygen saturation were significantly lower in subjects with IR (76% vs. 85%, P = 0.004 and 90.4% vs. 93.0%, P = 0.02). In multivariate analysis, the percent of time below 90% saturation [%T < 90]) (P = 0.04) was independently associated with IR. CONCLUSIONS: Our results suggested that metabolic syndrome prevalence increased with severity of OSAHS and vice versa. Nocturnal hypoxic episodes in OSAHS patients could be a risk factor for developing hypertension and IR. PMID- 21034273 TI - Pyridoxine restores endothelial cell function in high glucose. AB - OBJECTIVE: Aminoguanidine, which inhibits the formation of advanced glycosylation end products, can restore the ability of endothelial cells to align and elongate in response to shear stress when that ability is lost during culture in high glucose conditions. This study tests whether aminoguanidine can also restore migratory ability of endothelial cells and whether pyridoxine, a stable form of vitamin B6, can restore migratory ability and ability to align and elongate in response to shear. METHODS: Human aortic endothelial cells were cultured in normal glucose (5.5 mM), 17.5 mM glucose, and 30.5 mM glucose in the presence or absence of 5 mM aminoguanidine or varying concentrations of pyridoxine (10-1,000 mg/L). Assay of percent closure of a scrape wound after 24 h quantified migratory ability, and alignment and elongation under flow at 10 dynes/cm(2) quantified response to shear stress. RESULTS: Aminoguanidine (5 mM) fully restores and pyridoxine (100 mg/L, 0.6 MUM) partially restores migratory ability of cells cultured in 30.5 mM glucose. Pyridoxine (100 mg/L) fully restores the migratory ability of cells cultured in 17.5 mM glucose. Pyridoxine (100 mg/L) fully restores endothelial cell alignment and elongation and response to shear stress at 30.5 mM glucose. CONCLUSIONS: Pyridoxine, at dosages known to be safe from previous studies (<250 mg/day) can restore migratory ability and shear stress response to endothelial cells cultured in high-glucose conditions. This indicates that pyridoxine is a potential candidate for treatment of diabetic ulcers and atherosclerosis in diabetes due to the link between these pathologies and endothelial dysfunction in diabetes. PMID- 21034274 TI - Is concomitant cholecystectomy safe during laparoscopic anti-reflux surgery? AB - OBJECTIVE: The goal of this study is to prospectively evaluate the safety of concomitant cholecystectomy during laparoscopic anti-reflux surgery (LARS). METHODS: A total of 1000 patients underwent LARS between May 2004 and August 2009. Patients who had a LARS procedure alone were defined as group A and those who had cholecystectomy during the LARS were defined as group B. All data, including demographics, operative details, perioperative complications, and outcomes, were recorded to the prospective database. Chi-square and t-test were used for statistical analysis. RESULTS: There were 934 (93.4%) patients in group A and 66 (6.6%) in group B. Cholelithiasis (n = 48) and gallbladder polyp larger than 10 mm (n = 18) were the indications for cholecystectomy. Demographic characteristics were similar among the groups. There were no mortality and conversion. The mean operating time was 50 minutes for group A and 80 minutes for group B (P = 0.0001). The mean hospital stay was 1 day for each group. The mean follow-up was 35 and 38 months for groups A and B, respectively (P = 0.195). Esophageal perforation, jejunal perforation, and pulmonary emboli were the major complications and were seen only in group A (P = 0.790). All other peroperative minor complications and postoperative dysphagia, bloating, and reflux recurrence were similar between the two groups (P > 0.05). CONCLUSION: LARS and cholecystectomy can be performed safely during the same session without increasing the rates of morbidity and recurrence of reflux. PMID- 21034275 TI - Early experience with totally robotic Roux-en-Y gastric bypass for morbid obesity. AB - BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (RYGBP) for morbid obesity is a challenging operation. The application of robotic techniques has been shown to ease the technical difficulties and reduce perioperative morbidity, mainly because it facilitates the construction of the gastrojejunal anastomosis (GJ). Robotic laparoscopic RYGBP (LRYGBP) has been reported either as totally robotic with manual suturing of the GJ or as robotically assisted with the use of the robot only for the construction of the GJ. A totally robotic LRYGBP with a combined stapled and manual GJ has never been reported. PATIENTS AND METHODS: Nine consecutive patients underwent totally robotic LRYGBP. The GJ was fashioned with a combination of the linear stapler and manual suturing. RESULTS: Mean preoperative body mass index was 45.3 +/- 4.7 kg/m(2). In 1 case, we had to undock the Da Vinci Surgical System at the time of the jejunojejunostomy due to unfavorable ergonomics. Mean time to dock the robot was 16.3 +/- 3.3 minutes, whereas mean total operative time was 197.2 +/- 12.3 minutes. Immediate postoperative morbidity and mortality equaled zero. One patient developed a stenosis of the GJ amenable to endoscopic dilatation. The mean excess weight loss rate 1-year postoperative was 79% +/- 15%. CONCLUSION: Totally robotic LRYGBP can duplicate precisely any conventional technique without any compromise in operative time, short- or long-term results. PMID- 21034276 TI - Implications of mobility impairment on the diagnosis and treatment of breast cancer. AB - BACKGROUND: Among women with chronic, preexisting mobility impairments, we sought to explore how their mobility difficulties affected the diagnosis and treatment of early-stage breast cancer METHODS: This is a qualitative analysis of transcripts from in-depth in-person or telephone interviews with 20 English speaking women who had early-stage breast cancer, were <60 years of age, and had chronic difficulty walking or used wheeled mobility aids at the time of their breast cancer diagnoses RESULTS: Nine women were disabled by polio as children or had postpolio syndrome, 3 had cerebral palsy, 3 had spinal cord injury, and 5 had other conditions. Most women reported difficulty obtaining mammograms, primarily because of inaccessible equipment, positioning problems, and difficulties with uncontrollable movements. Many women made decisions about surgical approach and chemotherapy by explicitly considering how various therapies would affect their arms, which are essential to their mobility (they use ambulation aids, self propel manual wheelchairs, or otherwise rely on their arms for mobility or safety). Managing at home after surgery posed major mobility challenges, especially for women who lived alone. Several women reported feeling they suffered more chemotherapy side effects than do women without mobility problems. Weight gains with endocrine therapy compromised the mobility of several women. CONCLUSIONS: Increasing numbers of American women are living with mobility disabilities and entering age ranges with increased risks of breast cancer. Mobility impairments can affect women at every point during early-stage breast cancer diagnosis, therapy, and recovery. Clinicians must consider women's mobility functioning in making therapeutic recommendations to women with impaired mobility who develop breast cancer. PMID- 21034278 TI - Clinical and financial impact of a palliative care program at a small rural hospital. AB - BACKGROUND: Palliative care (PC) programs attempt to improve communication and symptom management, and a consequence has been lower cost of in-hospital death. To date, most research has focused on urban large hospitals. This study reports the clinical and financial impact of a new palliative care service at a 76-bed nonprofit hospital located in rural Virginia, Rappahannock General Hospital (RGH). METHODS: The RGH PC program started in 2006 with a part-time physician on grant support. We collected the number of consults, physician billing and receipts, and calculated the impact on the hospital's charges for patients treated with concurrent palliative care. RESULTS: The program was well accepted clinically with referrals from most of the palliative care physician's colleagues. After the first year of operation, she has about 10 new consults and a total of 45 visits per month. Billings for this year are projected to be $59,070 and her collections are projected to be $29,604 (50%). Hospital charges per patient are reduced about $400 per day, or 25%, after a palliative care consultation, which sums to $80,000 to $130,000 yearly. Referrals to home hospice increased. CONCLUSIONS: Palliative care by a dedicated practitioner can work in rural areas. The income will be small, but the operational and financial benefits to the hospital can be significant. This is better care at a cost that rural hospitals and practitioners can afford. PMID- 21034277 TI - Studying the use of oral contraception: a review of measurement approaches. AB - BACKGROUND: Although oral contraception (OC) misuse is presumed to play an important role in unwanted pregnancy, research findings have often been equivocal, perhaps reflecting unaddressed inconsistencies in methodological approaches. METHODS: Using established databases, we performed a systematic review of measurement methods for OC use using primary research reports published from January 1965 to December 2009. RESULTS: Terminology used to describe OC use, which included "continuation," "compliance," and "adherence," differed across studies and was rarely defined. The majority of studies (n = 27 of 38, 71%) relied solely on self-report measures of OC use. Only two reports described survey or interview questions, and reliability and validity data were seldom described. More rigorous measurement methods, such as pill counts (electronic or manual), serum and urinary biomarkers, and pharmacy records, were infrequently employed. Nineteen studies simultaneously used more than one method, but only three studies compared direct and indirect methods. CONCLUSIONS: The lack of a consistent, well-defined measurement of OC use limits our understanding of contraceptive misuse and related negative outcomes. Future research should clarify terminology, develop standardized measures, incorporate multimethod approaches with innovative methods, and publish details of measurement methods. PMID- 21034280 TI - Rapid identification of common beta-thalassemia mutations in the Chinese population using duplex or triplex amplicon genotyping by high-resolution melting analysis. AB - beta-Thalassemia is one of the most prevalent inherited diseases in China. To date, over 20 beta-thalassemia mutations have been identified in the Chinese population, and four mutations [CD41-42 (-4 bp), IVS-2-654C->T, CD17A->T, and 28A->G] account for approximately 90% of the cases. Therefore, the exploration of simple, reliable, and rapid approaches for molecular detection of these common mutations is important for prevention and early diagnosis of the disease. High resolution melting (HRM) analysis is a new technique for mutation detection that has the advantages of rapidity, accuracy, and convenience. Building on one amplicon genotyping by HRM analysis, we developed duplex and triplex amplicon genotyping to simultaneously identify these common beta-thalassemia mutations in patients or carriers. Two or three sets of primers were combined to conduct duplex or triplex amplicon genotyping, which distinguished a variety of genotypes by HRM based on the melting curve shapes. Seventy-one DNA samples from beta thalassemia traits or patients were analyzed using the described approaches and 65 were identified to carry the 4 common beta-thalassemia alleles including 56 heterozygous mutations [23 for CD41-42 (-4 bp), 18 for IVS-2-654C->T, 11 for CD17A->T, and 4 for -28A->G], 3 homozygous mutations for IVS-2-654C->T, and 6 compound heterozygous mutations [CD41-42 (-4 bp)/IVS-2-654C->T (4 cases), -28A >G/CD17A->T (1 case), IVS-2-654C->T/CD17A->T (1 case)]. The whole procedure for mutation detection was completed within only half an hour. The results derived from HRM analysis were fully in accordance with sequencing. We suggest this rapid and accurate method for molecular screening to detect the common beta-thalassemia mutations in the Chinese population as well as in other ethnic groups and nationalities in which the above four beta-thalassemia alleles are prevalent. PMID- 21034279 TI - Changes in medical care at a pediatric oncology referral center after placement of a do-not-resuscitate order. AB - OBJECTIVE: Parents may fear that a do-not-resuscitate (DNR) order will result in reduction of the level, quality, and priority of their child's medical care. We therefore assessed medical care that was continued, added, and discontinued after a DNR order was placed in the medical record. PATIENTS/METHODS: Retrospective review of the charts of 200 pediatric oncology patients at St. Jude Children's Research Hospital who died between July 1, 2001 and February 28, 2005, were younger than 22 years old at death, and had a documented DNR order. Medical interventions that were added (between the DNR order and death), continued (not discontinued between 24 hours before and 72 hours after DNR), and discontinued (within 72 hours after DNR) were identified and compared by using binomial proportions. RESULTS: With the exception of chemotherapy, the studied medical interventions that patients were receiving at the time of the DNR order were continued in 66.7% to 99.3% of cases. Chemotherapy was continued in 33.3%. The most frequently added interventions were oxygen, steroids, and pain medicine. The most frequently discontinued interventions were laboratory draws, chemotherapy, antibiotics, and parenteral nutrition. CONCLUSIONS: In this cohort of pediatric oncology patients, the medical interventions being received were continued with a high frequency after placement of a DNR order. Chemotherapy was continued only in a minority of patients, possibly signifying a shift in goals. These findings may help to reassure families that a DNR order need not result in a change in any of their child's medical therapies which appropriately advance the defined goals of care. PMID- 21034281 TI - Non-responsiveness to intervention: children with autism spectrum disorders who do not rapidly respond to communication interventions. AB - OBJECTIVE: Providing a detailed description of two participants who failed to acquire functional communication skills following a verbal modelling intervention and Picture Exchange Communication System (PECS) training. METHODS: Single-case research; Independent verbal requests, imitated verbal requests, word approximations and independent picture requests were assessed in a toddler and a pre-schooler with autism before and during two interventions. RESULTS: Although both participants used some vocalizations over the course of the study, experimental control was not demonstrated and the participants did not acquire a functional communication system prior to the cessation of intervention. CONCLUSIONS: Future research should include additional, detailed reports that provide insight to why some children with autism do not respond to particular communication interventions and should investigate the pairing of particular child characteristics with targeted interventions. PMID- 21034282 TI - Association of birth factors with subsequent developmental disability: effectiveness in predicting severity as measured by the PEDI. AB - OBJECTIVE: To determine if specific birth factors can be used to predict a subsequent disability and severity level in self-care, mobility and social function as measured by the Paediatric Evaluation of Disability Inventory (PEDI). DESIGN: This cross-sectional study design used retrospective data from birth records and concurrent data from PEDI scores. METHOD: Sixty children (20 per group) were selected representing groups consistent with typical development, sensory processing disorders or physical disability. Mean age was 56 months; there were 32 males. Information extracted from birth records was compared to PEDI scores. RESULTS: Univariate ANOVA showed differences among groups for PEDI scores (p < 0.001) and birth factors (p < 0.001). A forward logistic regression analysis revealed gestational age and 5-minute Apgar scores as potential predictors of PEDI scores. CONCLUSION: Findings indicated that two birth factors were related to later functional performance, but only in children with sensory processing deficits. PMID- 21034283 TI - The effects of inattention/impulsivity and ASD symptom severity on social skills in toddlers. AB - OBJECTIVE: The aim of the current study was to examine the effects of symptom severity of ASD and symptom severity of inattention and impulsivity in toddlers to determine the potential impact on social skills. METHODS: A total of 240 toddlers diagnosed with ASD, ranging in age from 17-36 months, were included in this study. Parents or legal guardians were administered measures assessing for symptoms of ASD, symptoms of psychopathology and social skills. RESULTS: A significant interaction was found, indicating that toddlers with less severe symptoms of ASD and of inattention/impulsivity had better social skills. In contrast, toddlers with more severe symptoms of ASD and inattention/impulsivity had the most deficits in social skills. CONCLUSION: These results further confirm that a multidimensional approach to assessment is needed and that comorbid psychopathology symptoms and social skills targets should be a focus of assessment and intervention. PMID- 21034284 TI - Investigating the efficacy of an attention training programme in children with foetal alcohol spectrum disorder. AB - OBJECTIVE: The current study investigated the efficacy of a direct intervention programme aimed at improving attention abilities in children with foetal alcohol spectrum disorder (FASD). METHODS: The Computerized Progressive Attention Training (CPAT) program is an intervention which targets proposed attention networks. CPAT task difficulty automatically adjusts based on participant performance. Ten children aged 6-15 with FASD completed an average of 16 hours of intervention over ~9 weeks at school, aided by a research assistant providing metacognitive strategies and support. RESULTS: Pre- and post-intervention assessments indicate significant improvement on several attention measures including sustained attention and selective attention. In addition, several measures of spatial working memory, math fluency, and reading fluency also significantly increased, suggesting that better attention leads to better cognitive performance. CONCLUSION: Results provide support for the use of computerized attention training materials as part of an effective intervention for cognitive performance in children with FASD. PMID- 21034285 TI - An examination of differences in symptom endorsements of autism spectrum disorders: a comparison between mothers and fathers. AB - OBJECTIVE: Best assessment practices for Autism Spectrum Disorders (ASD) incorporate both multimodal and multi-informant assessments. However, differences in symptoms reports from multiple informants can lead to diagnostic decision making problems. METHODS: Thus, the purpose of this paper was to examine differences in the reports of symptoms of ASD between parents (i.e. mothers and fathers) of children and adolescents that met research criteria for an ASD and additionally for a group of children that were typically-developing (n=39). RESULTS: There were differences in the number of symptoms endorsed between mothers and fathers. CONCLUSION: Implications of the current findings are discussed. PMID- 21034286 TI - Technology-assisted messaging opportunities for two persons emerged from a minimally conscious state and showing extensive motor disabilities. AB - OBJECTIVE: To extend the assessment of a special messaging technology with two adults emerged from a minimally conscious state and showing extensive motor disabilities as well as limited or no oral/verbal skills. METHOD: The study involved a non-concurrent multiple baseline design across participants. Both participants started with baseline in which the technology was not available, and continued with intervention in which the technology was used. The technology involved a net-book computer provided with specific software, a global system for mobile communication (GSM) modem, microswitches, and pre-recorded lists of persons and messages. RESULTS: Both participants learned to send out and receive (listen to) messages independently during the intervention. They sent out a mean of three or three and a half messages and received a mean of one and a half messages per 20-minute session. CONCLUSIONS: Special messaging technology may help post-coma persons with multiple disabilities engage in basic communication with distant partners. PMID- 21034287 TI - Adapting a computer-assisted program to help a post-coma man with extensive multiple disabilities choose stimulus events. AB - OBJECTIVE: To adapt an existing computer-assisted program to help a post-coma man with extensive multiple disabilities choose between stimulus events. METHOD: An adapted version of the program assessed in this study presented the man with 7 second samples of preferred and non-preferred stimuli, without questions, and allowed him to choose any of them through a vocalization response. The man's use of this response to choose a stimulus sample led the computer to present the matching stimulus for 20 seconds. The same response used immediately after the end of the 20-second stimulus presentation led to the repetition of that presentation. RESULTS: The adapted program version was effective in promoting high levels of choice among preferred stimuli and virtually no responding in relation to non-preferred stimuli. Indices of happiness were frequent during the program sessions. CONCLUSIONS: Computer-assisted programs for stimulus choice might be successfully adapted to post-coma persons with extensive disabilities. PMID- 21034288 TI - Applying the ICF framework to study changes in quality-of-life for youth with chronic conditions. AB - OBJECTIVE: The objective of this paper is to describe how the ICF framework was applied as the foundation for a longitudinal study of changes in quality-of-life (QoL) for youth with chronic conditions. METHOD: This article will describe the study's aims, methods, measures and data analysis techniques. It will point out how the ICF framework was used--and expanded upon--to provide a model for studying the impact of factors on changes in QoL for youth with chronic conditions. Further, it will describe the instruments that were chosen to measure the components of the ICF framework and the data analysis techniques that will be used to examine the impact of factors on changes in youths' QoL. CONCLUSIONS: Qualitative and longitudinal designs for studying QoL based on the ICF framework can be useful for unraveling the complex ongoing inter-relationships among functioning, contextual factors and individuals' perceptions of their QoL. PMID- 21034289 TI - Mechanisms of action of topical 5-fluorouracil: review and implications for the treatment of dermatological disorders. AB - Topical 5-fluorouracil has proved to be a useful therapy since its discovery nearly 50 years ago for the treatment of a range of cancers (e.g. skin, colorectal, breast) and dermatological conditions (e.g. cancerous and precancerous conditions such as actinic keratosis, benign tumors, nail psoriasis, mycosis fungoides, and porokeratoses). As a result of the enduring utility in these conditions, the mechanism of action of 5-fluorouracil has been studied extensively in vivo and in vitro. This review provides an overview of the history and general mechanism of action of 5-fluorouracil and discusses the dermatological implications of the drug, including systemic absorption, selectivity for abnormal skin, targeted delivery, and skin-specific molecular effects. Considerations of 5-fluorouracil treatment in specific dermatological settings are also discussed, as well as recent findings of a role for 5 fluorouracil in the treatment of photoaging. PMID- 21034290 TI - Ustekinumab decreases work limitations, improves work productivity, and reduces work days missed in patients with moderate-to-severe psoriasis: results from PHOENIX 2. AB - OBJECTIVE: To assess the effect of ustekinumab on productivity and work limitations among 1230 psoriasis patients treated with ustekinumab 45 mg or 90 mg or placebo during the Phase III PHOENIX 2 trial. METHODS: The self-administered Work Limitations Questionnaire (WLQ) was used to determine the on-the-job limitations at baseline and weeks 12 and 24. Productivity was assessed using a Visual Analog Scale (VAS), and the number of work days missed due to psoriasis was recorded. RESULTS: At baseline, work limitations and productivity were similar across treatment groups. At week 12, improvement in productivity VAS scores was significantly (p < 0.001) higher in the 45 mg (72.6%) and 90 mg (71.4%) ustekinumab groups versus placebo (no change), and the proportion of patients who missed work days was significantly lower (2.0% for each ustekinumab group vs 8.3% for placebo; p < 0.001). Mean improvements from baseline to week 12 were greater with ustekinumab than with placebo for WLQ domains, including time management (6.6/9.1 vs -0.7), mental-interpersonal (7.8/7.5 vs -1.1), and output demands (6.8/7.0 vs -1.1) (p < 0.001 for ustekinumab 45 mg/90 mg vs placebo). Improvements were maintained through week 24. CONCLUSIONS: Ustekinumab 45 mg or 90 mg significantly increased productivity, reduced work days missed, and improved work limitations compared with placebo in patients with moderate-to severe psoriasis. PMID- 21034291 TI - The efficacy of 5% trichloroacetic acid cream in the treatment of cutaneous leishmaniasis lesions. AB - INTRODUCTION: Cutaneous Leishmaniasis (CL) is an endemic disease in Iran. Based on the results of our previous study, this study was designed as a pilot trial to evaluate the effect of 5% trichloroacetic acid (TCA) cream in the treatment of leishmaniasis lesions. METHODS: 16 patients with positive smear for leishmaniasis were randomly selected for treatment with 5% TCA cream, twice a day for 8 weeks or up to complete healing of the lesions. Scar size was measured 6 months after complete epithelization of the lesions. RESULTS: Mean area of the lesions was 38.81+ 81.9 mm(2) before treatment and 3.6 + 9.1 mm(2) at 6 month follow up period. Complete cure was achieved in 1 patient (6.3%) at week 2, 13 patients (86.7%) at week 7, and in all patients at week 8. There was no serious adverse reaction in none of the patients. CONCLUSION: Decreasing the scar size and the low cost are two promising aspects in introducing 5% TCA cream as a potential alternative for intralesional glucantime in the treatment of CL. Considering the self limiting nature of the disease, this effect should be assessed further through a double blind randomized controlled trial. PMID- 21034293 TI - The impact of cortisol reactivity to acute stress on memory: sex differences in middle-aged people. AB - Stress has been identified as a main factor involved in the cognitive changes that occur during the aging process. This study investigated sex differences in the relationship between the magnitude of the acute stress-induced salivary cortisol response and memory performance among middle-aged people. To this end, 16 men and 16 women (aged 54-72 years) were exposed to the Trier Social Stress Test and a control condition in a crossover design. Afterwards their memory performance was measured using a standardized memory test (Rey's Auditory Verbal Learning Test). Only among women, there was an acute impact of stress on memory performance and a significant relationship between a higher cortisol response to the stressor and poorer memory performance in both the stress and control conditions. Additionally, a poorer memory performance was related to earlier timing of sexual maturation (age at menarche), which was also marginally related to higher cortisol reactivity to stress. These results confirm that sex is a critical factor in the relationship between cortisol and poor memory performance. Furthermore, the findings emphasize a strong link between the individual cortisol response to stress and memory functioning among postmenopausal women. PMID- 21034292 TI - Juvenile offspring of rats exposed to restraint stress in late gestation have impaired cognitive performance and dysregulated progestogen formation. AB - Gestational stress may have lasting effects on the physical and neurocognitive development of offspring. The mechanisms that may underlie these effects are of interest. Progesterone and its 5alpha-reduced metabolites, dihydroprogesterone and 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP), maintain pregnancy, have neurotrophic effects, and can enhance cognitive performance. We hypothesized that some of the deleterious effects of gestational stress on the cognitive performance of offspring may be related to progestogen formation. Pregnant rat dams were exposed to restraint under a bright light (thrice daily for 45 min) on gestational days 17-21 or were minimally handled controls. Dams that were exposed to restraint had lower circulating levels of 3alpha,5alpha-THP and significantly greater concentrations of corticosterone at the time of birth than did control dams. Male and female offspring, that were gestationally stressed or not, were cross-fostered to non-manipulated dams. Between postnatal days 28-30, offspring were assessed for object recognition, a prefrontal cortex (PFC)-dependent cognitive task. Restraint-exposed offspring performed more poorly in the object recognition task than did control offspring, irrespective of sex. As well, progesterone turnover to its 5alpha-reduced metabolites in the medial PFC (but not the diencephalon) was significantly reduced among restraint-exposed, compared to control, offspring. Progesterone turnover, and levels of 3alpha,5alpha-THP, positively correlated with performance in the object recognition task. Thus, restraint stress in late pregnancy impaired cognitive development and dysregulated progestogen formation in brain. PMID- 21034294 TI - C-reactive protein polymorphisms are associated with the cortisol awakening response in basal conditions in human subjects. AB - Cortisol affects the acute-phase response, but it is unknown whether C-reactive protein (CRP), an acute-phase reactant, also affects hypothalamus?pituitary?adrenal axis activity. In the present study, associations were explored between CRP haplotypes with plasma CRP concentrations and basal salivary cortisol level. We included 266 physically healthy Caucasian subjects (103 females and 163 males) aged between 18 and 65 years of whom 94 had a psychiatric disorder in a genetic association study. Six tag single-nucleotide polymorphisms capturing the common genetic variation of the CRP gene were genotyped (i.e. rs2808628, rs2808630, rs1205, rs1800947, rs1417938, and rs3091244) to yield common CRP haplotypes. Plasma CRP concentrations, the salivary cortisol awakening response (CAR) (0, 30, 45, and 60?min after awakening), and the diurnal cortisol decline (11:00, 15:00, 19:00, and 23:00 h) were assessed for 2 days. rs2808628, rs1205, rs1417938, and rs3091244 showed expected associations not only with CRP concentrations, but also with salivary cortisol levels during the CAR. Five well-characterized CRP haplotypes were arranged in ascending order according to increasing CRP levels. There was an inverse linear association between CRP haplotypes and cortisol levels during the CAR, but no association with the diurnal cortisol decline. Hence, genetic variants in the CRP gene that are associated with lifetime plasma CRP levels were also associated with salivary cortisol levels after awakening, in basal, non inflammatory conditions. PMID- 21034295 TI - The effects of post-encoding stress on recognition memory: examining the impact of skydiving in young men and women. AB - Prior studies have indicated that post-encoding stress can protect memories from the effects of forgetting, and this has been taken as evidence that stress facilitates memory consolidation. However, it is not known whether stress acts by directly influencing the strength of the underlying memories or whether it influences the generation process that plays a critical role in tests such as free recall. To address this issue, we examined the effects of stress produced by skydiving on recognition memory for negative and neutral pictures. Relative to a non-stress control condition, post-encoding stress in males was found to increase recognition memory for neutral pictures. However, stress was not found to improve recognition for emotional pictures, nor was it found to influence recognition memory in female participants. Additional analysis of recognition performance suggested that stress increased familiarity-based recognition rather than recollection. This study indicates that stress can improve familiarity-based recognition, thus showing that stress directly increases the strength of the underlying memories. PMID- 21034296 TI - Eugenol as an anti-stress agent: modulation of hypothalamic-pituitary-adrenal axis and brain monoaminergic systems in a rat model of stress. AB - Stress is the leading psychopathological cause for several mental disorders. Physiological and psychological responses to stress are mediated by the hypothalamic?pituitary?adrenal (HPA), sympathoadrenal system (SAS), and brain monoaminergic systems (BMS). Eugenol is reported to substantially modulate brain functions by regulating voltage-gated cation channels and release of neurotransmitters. This study was designed to evaluate the anti-stress effect of eugenol in the 4-h restraint model using rats. Ulcer index was measured as a parameter of the stress response. HPA axis and the SAS were monitored by estimating plasma corticosterone and norepinephrine (NE), respectively. Analysis of NE, serotonin (5-HT), dopamine, and their metabolites in discrete brain regions was performed to understand the role of BMS in the anti-stress effect of eugenol. Stress exposure increased the ulcer index as well as plasma corticosterone and NE levels. Eugenol pretreatment for 7 days decreased the stress-induced increase in ulcer index and plasma corticosterone but not NE levels, indicating a preferential effect on the HPA axis. Furthermore, eugenol showed a ?U?-shaped dose?response curve in decreasing ulcer index and plasma corticosterone levels. Eugenol also reversed the stress-induced changes in 5-HT levels in all brain regions, whereas NE levels were reversed in all brain regions except hippocampus. These results suggest that eugenol possesses significant anti stress activity in the 4-h restraint model and the effect is due to modulation of HPA and BMS. PMID- 21034297 TI - Effects of stressful life events on human brain structure: a longitudinal voxel based morphometry study. AB - Although stressful life events (SLEs) have been associated with an increased risk of illness and mental disorder, their impact on brain anatomy remains poorly understood. Using a longitudinal design, we tested the hypothesis that SLEs are significantly associated with changes in gray matter volume (GMV) in brain regions previously implicated in post-traumatic stress disorder (PTSD) in a group of clinically healthy adults. Magnetic resonance imaging was used to acquire an anatomical scan from 26 subjects (13 males and 13 females; mean age +/- SD: 25.2 +/- 4.3 years), with no psychiatric diagnosis, at two time points with a 3-month interval. Voxel-based morphometry was used to examine an association between SLEs and gray matter changes during this period. The number of SLEs was associated with a decrease in GMV in the anterior cingulate, hippocampus, and parahippocampal gyrus (p < 0.001). In contrast, there were no areas where the number of SLEs was associated with an increase in GMV. These results provide evidence that, in adults with no formal psychiatric diagnosis, SLEs are associated with GMV decreases in a subset of regions implicated in PTSD, and that these alterations can be observed within a period as short as 3 months. PMID- 21034298 TI - Abnormal diurnal pattern of cortisol secretion in patients after aneurysmal subarachnoid hemorrhage. AB - Substantial evidence suggests that impairment of the hypothalamus?pituitary system can occur following an aneurysmal subarachnoid hemorrhage (aSAH). Given that the diurnal cortisol rhythm is primarily controlled by the hypothalamus?pituitary system, this study examined whether changes in diurnal cortisol rhythm occurred after aSAH. Cortisol concentrations were measured in the saliva samples collected from patients after aSAH and other types of cerebral hemorrhage (non-aSAH) in the post-awakening period and at night (21:00?h), and the cortisol awakening response (CAR) and diurnal cortisol decline were determined. The area under the cortisol curve from immediately after to 45?min after awakening (CARauc) in the aSAH patient group was comparable to that in the non-aSAH or healthy control groups. However, an obvious cortisol peak was not found after the awakening period, and the morning/nighttime cortisol ratio in the aSAH patient group was significantly lower than that in other examined groups due to higher nighttime cortisol concentrations. In aSAH patients, the CARauc and nighttime cortisol concentrations were negatively correlated with the Fisher CT grade. These results indicate that the diurnal cortisol rhythm is not regulated normally after aSAH, and cortisol secretory activity decreases as the volume of subarachnoid bleeding increases. Our findings will be helpful to understand altered hypothalamus?pituitary?adrenal axis function after aSAH. PMID- 21034299 TI - Chronic stress and environmental enrichment as opposite factors affecting the immune response in Japanese quail (Coturnix coturnix japonica). AB - Procedures in the commercial production of animals involve stressful situations which lessen the animal's welfare. This study on Japanese quail evaluated whether an environmental enrichment manipulation can affect avian immune responses and if combined with a chronic stressor exposure can help to counteract the negative effects of stress on the immune system. Potential gender effects were also considered. After hatch, half of the birds were housed in non-enriched boxes and half were housed in environmentally enriched boxes. From day 33 to 42 of age, all birds within half of the non-enriched and enriched boxes remained undisturbed while the other half were daily exposed to a 15 min restraint stressor (chronic stressor). The inflammatory response (lymphoproliferation after phytohemagglutinin-p), percentage of lymphocytes, heterophil/lymphocyte (H/L) ratio and primary antibody response against sheep red blood cells were assessed. The chronic stressor application and the enrichment procedure, respectively, either increased or reduced the four immunological parameters evaluated and always in opposite directions. Males consistently showed lower antibody titres than females and presented the highest H/L ratio in response to the stressor when reared in the non-enriched environment. The findings indicate that submitting these animals to an enriched environment can be effectively used to improve their immune response and to reduce the detrimental effects of a stressor exposure. PMID- 21034300 TI - Brown adipose tissue redox status in response to dietary-induced obesity associated oxidative stress in male and female rats. AB - Obesity is linked to systemic oxidative stress and, although brown adipose tissue (BAT) plays a crucial role in energy balance, BAT redox status effects on obesity have not been studied previously. Female rats exhibit a greater BAT thermogenic capacity, attributed to enhanced mitochondrial differentiation, than males. The aim of this study was to investigate whether the mitochondrial sexual dimorphism is related to differences in BAT redox status and to assess its role in the regulation of body weight gain in response to chronic high fat diet (HFD) feeding. Ten-week-old Wistar rats of both genders were fed a pelleted control diet or HFD for 26 weeks. Although mitochondria of female rats produced higher levels of hydrogen peroxide than those of males, females exhibited lower oxidative damage, attributed to greater glutathione peroxidase activity and higher glutathione content. In response to HFD, body weight increased markedly in females, but oxidative capacity increased only in males, thus maintaining improved BAT redox status compared with females. In conclusion, the sexual dimorphism in BAT redox status found in control animals is attenuated by the HFD. The enhanced oxidative capacity of HFD males can be related to their greater resistance to body weight gain. PMID- 21034301 TI - Fear-related pictures deteriorate the performance of university students with high fear of snakes or spiders. AB - Despite research regarding emotional processing, it is still unclear whether fear evoking stimuli are processed when they are irrelevant and when attention is oriented elsewhere. In this study, 63 healthy university students with high fear from snakes or spiders participated in two different experiments. In an emotional modification of the spatial cueing task, 31 subjects (5 males) were asked to detect a target letter while ignoring a neutral or fear-related distracting picture. The distribution of attention was independently manipulated by a spatial cue that preceded the appearance of the picture and the target letter. In an emotional modification of the cognitive load paradigm, 32 subjects (4 males) were asked to discriminate between two target letters, while ignoring a central neutral or fear-related picture, and additional 1, 3, or 5 distracting letters that created a varied attentional load. Fear-related pictures interfered with the performance of highly fearful participants, even when the pictures were presented outside the focus of attention and when the task taxed attentional resources. We suggest that highly fearful individuals process fear-related information automatically, either inattentively or with prioritized attention capture over competing items, leading to deteriorated cognitive performance. Different results were shown in healthy individuals while processing negative--but not phobic- pictures, suggesting that emotional processing depends on the fear value of the stimulus for a specific observer. PMID- 21034302 TI - Clinical review: Update on treatment of inflammatory macular edema. AB - The aim of this review is to summarize the recent developments in the treatment of inflammatory macular edema (ME). Inflammatory ME represents a major cause of visual loss in uveitis and its adequate management is crucial for the maintenance of useful vision in patients with uveitis. Recent studies favor early treatment of inflammatory ME, even in patients with full visual acuity. After recapitulating the standard treatment modalities for inflammatory ME the authors address novel corticosteroid implants. They review the literature on the efficacy of anti-VEGF agents for inflammatory ME and point out their beneficial, but transient effects. Further, they present recent data on the value of systemic biologics in uveitic ME and evaluate the effectiveness of vitrectomy. Finally, they propose an algorithm for the treatment of inflammatory ME and point out that the individual risk-benefit ratio, especially with systemic immunosuppressive therapy, should always be considered. PMID- 21034303 TI - Retinal vasoproliferative granulomatous lesion associated with hand pyoderma caused by Streptococcus pyogenes. AB - PURPOSE: To report a retinal vasoproliferative granulomatous lesion in association with pyoderma. DESIGN: Single case report. METHODS: A 32-year-old woman had blurred central vision in the right eye, concurrent with pyoderma of the fingers of both hands, 2 days later followed by fever. RESULTS: The patient had a granulomatous lesion in the upper retina, which caused leakage, leading to subretinal and intraretinal accumulation of hard exudates in the posterior pole, together with periphlebitis extending over the wider area of the retina. The culture of the pyodermic lesion detected Streptococcus pyogenes. With the 2-month course of amoxicillin-clavulanate, combined with prednisolone tapered from 30 mg daily, the visual acuity (decimal fraction) in the right eye returned from 0.01 (logMAR = 2) to 0.9 (logMAR = 0.1). However, after the discontinuation of the antibiotics and prednisolone, the retinal lesion became more vasoproliferative and caused leakage to reduce the vision again. The leakage was remedied by laser photocoagulation to the retinal lesion. CONCLUSIONS: The retinal granulomatous lesion was caused by streptococcal infection in pyoderma and later became more vasoproliferative with macroaneurysms and microaneurysms even after the initial subsidence of the lesion with antibiotics treatment. PMID- 21034304 TI - Occlusive vasculitis and optic disk neovascularization associated with neuroretinitis. AB - PURPOSE: To report a case of neuroretinitis associated with ischemic nasal branch retinal vein occlusion, periphlebitis, and neovascularization of the optic disk. METHODS: Case report. RESULTS: A 32-year-old man presented with a typical image of neuroretinitis, retinal hemorrhages and sheathing of the retinal veins in the nasal retina. His left hand had been bitten by a kitten 8 weeks before. Serology for Bartonella henselae was negative. On the 6th week of follow-up, optic disk neovascularization developed, which required retinal photocoagulation. Photocoagulation was performed again at the 12th and 18th week revision since further new vessels had developed. At the 32nd week of follow-up neovascularization had regressed. CONCLUSIONS: Neuroretinitis may be associated with severe complications such as retinal vascular occlusions and optic disk neovascularization. PMID- 21034305 TI - Effects of twice-daily topical difluprednate 0.05% emulsion in a child with pars planitis. AB - PURPOSE: To report the effects of twice-daily difluprednate in a child with pars planitis (PP). DESIGN/METHODS: Case report. RESULTS: PP was controlled with topical difluprednate for 1 year. Then an atypical pattern of steroid response- delayed, relatively sudden onset of recalcitrant ocular hypertension (OHT)--and posterior subcapsular cataract (PSC) formation necessitated alternative treatment. CONCLUSION: Although not a standard treatment, in select cases of PP topical difluprednate therapy could be a useful short-term treatment option while alternative treatments are considered or immunosuppressive agents build to therapeutic levels. Ophthalmologists must be aware of the potential for delayed onset of serious complications when using difluprednate. PMID- 21034306 TI - Behcet disease presenting with frosted branch angiitis. AB - The authors present a case of Behcet disease presenting with frosted branch angiitis. Frosted branch angiitis is a rare clinical finding and there are only two reported cases in the literature associated with Behcet disease. PMID- 21034307 TI - Thoughts and feelings of future working life as a predictor of return to work: a combined qualitative and quantitative study of sick-listed persons with musculoskeletal disorders. AB - PURPOSE: The main aim of this study was to describe the thoughts and feelings of future working life related to return to work (RTW) in sick-listed persons due to musculoskeletal disorders (MSD). Further aim was to compare these descriptions with the person's actual working situation 1, 5 and 10 years after a rehabilitation period. METHODS: This study consisted of two parts. The first part had an explorative design, and qualitative content analysis was chosen in order to analyse the response to an open question regarding future working life answered before, persons sick-listed due to MSD (n = 320), took part in a rehabilitation programme 10 years ago. The second part had a prospective design and quantitative analysis was used to compare the results of the qualitative analysis with RTW and the working situation 1, 5 and 10 years after baseline. RESULTS: Three categories emerged from the data with a total of nine subcategories. In the categories Motivation and optimism and Limitations to overcome, there were significantly more persons who had RTW 1 year after baseline when compared with the category Hindrance and hesitation. There were also some significant differences between the subcategories. CONCLUSIONS: The question, regarding thoughts and feelings of future working life, may be a simple screening method to predict RTW in persons sick-listed with MSD. This will guide the rehabilitation team to adjust the rehabilitation to each person's needs and facilitating RTW. PMID- 21034308 TI - Atypical presentation of cytomegalovirus endotheliitis: a case report. AB - PURPOSE: To describe an atypical case of cytomegalovirus (CMV) endotheliitis in a 74-year-old man who presented with chronic corneal edema without keratic precipitates (KPs) and intraocular pressure (IOP) elevation. DESIGN: Case report. METHODS: A complete ophthalmologic examination was performed. Polymerase chain reaction was used to test for herpes simplex virus, varicella zoster virus, and CMV DNA in aqueous humor samples to rule out viral endotheliitis. RESULTS: Severe bullous keratopathy was found in the temporal part of the cornea without KPs or elevated IOP. CMV DNA was detected. Corneal edema subsided with oral valganciclovior. CONCLUSIONS: CMV endotheliitis may present as corneal edema that lacks typical features, such as KPs or elevated IOP. PMID- 21034309 TI - Herpetic necrotizing retinitis following flucinolone acetonide intravitreal implant. AB - PURPOSE: To report a case of herpes simplex virus-induced herpetic necrotizing retinitis after placement of a flucinolone acetonide (Retisert) intravitreal implant. DESIGN: Interventional case report. METHODS: Retrospective chart review. RESULTS: A 22-year-old male with idiopathic unilateral panuveitis since 2002 that was intolerant of systemic immunosuppressive therapy received a flucinolone acetonide implant 6 years later. Intraocular inflammation was completely quiescent until 1 year following the implant, when he developed retinitis. To the authors' knowledge, this is the first reported case of polymerase chain reaction proven herpetic necrotizing retinitis following implantation of a Retisert device. CONCLUSIONS: Although rare, herpetic necrotizing retinitis can occur in the setting of local ocular immunosuppression with the Retisert intravitreal implant. This potential infection should be considered in the face of recurrent uveitis following Retisert implantation. PMID- 21034310 TI - Bacterial contamination of needles used for intravitreal injections: a prospective, multicenter study. AB - PURPOSE: To determine the incidence of bacterial contamination of needles used for intravitreal injections. METHODS: Patients undergoing intravitreal injections were enrolled prospectively. No pre-injection antibiotics were administered. Following povidone-iodine irrigation, conjunctival cultures were taken and the injection was performed. The needle was cultured. A dry control needle was exposed to the surgical field and cultured. RESULTS: No patients developed endophthalmitis. Eighteen injection needles (18%) yielded positive bacterial growth. The most commonly encountered organisms were Propionibacterium acnes (n = 8) and Staphylococcus epidermidis (n = 6). Four control needles showed positive growth, in 2 cases with the same organism as a matching positive used needle. The difference between contamination rates of used and control needles was significant (p = .002, McNemar's test). CONCLUSIONS: Bacterial contaminants are present on a substantial proportion of needles. Since the needle contacts both the ocular surface and the vitreous, it is possible that inoculation of the vitreous cavity occurs in such cases. PMID- 21034311 TI - Spectral domain optical coherence tomography and autofluorescence in a case of acute posterior multifocal placoid pigment epitheliopathy mimicking Vogt-Koyanagi Harada disease: case report and review of literature. AB - PURPOSE: To report a case of acute posterior multifocal placoid pigment epitheliopathy (APMPPE) with exudative retinal detachment, simulating acute Vogt Koyanagi-Harada (VKH) disease and to review relevant imaging literature. METHODS: Ophthalmologic examination, laboratory evaluation, fluorescein angiography, and B scan ultrasonography performed at baseline, as well as spectral domain optical coherence tomography (OCT) and fundus autofluorescence performed upon initial presentation and at 5-day, 1-month, and 3-month follow-up. RESULTS: OCT demonstrated outer retinal hyperreflectance and subretinal fluid in the acute phase that disappeared 5 days later. Choroidal thickening was noted on OCT and ultrasonography. Retinal pigment epithelium lesions were hypoautofluorescent acutely but became hyperautofluorescent later in the disease course. CONCLUSIONS: At presentation, there can be considerable overlap in both clinical and imaging findings in APMPPE mimicking acute VKH, making it difficult to differentiate these two entities. Cerebral spinal fluid analysis and follow-up examinations could help in arriving at proper diagnosis. PMID- 21034312 TI - Topiramate-induced bilateral anterior uveitis associated with hypopyon formation. AB - PURPOSE: To report a rare case of bilateral anterior uveitis with hypopyon formation following systemic topiramate use. MATERIALS AND METHODS: A 40-year-old woman with migraine headache who was under topiramate treatment referred with bilateral ocular pain and visual blurring. Physical examination disclosed shallow anterior chamber and high intraocular pressure in both eyes. Following discontinuation of topiramate a severe bilateral anterior uveitis with posterior synechiae and hypopyon developed. RESULTS: Ocular inflammation resolved with systemic and topical steroid. Because of severe cataract and synechiae formation she underwent phacoemulsification/posterior chamber intraocular lens implantation and visual acuity of both eyes improved to 20/25. CONCLUSION: Topiramate should be added to the list of drugs that may cause anterior uveitis and hypopyon formation. PMID- 21034313 TI - Dense fibrillar collagen matrices sustain osteoblast phenotype in vitro and promote bone formation in rat calvaria defect. AB - Two pure collagen materials were prepared from acidic collagen solutions at 5 and 40 mg/mL. Benefits of collagen concentration on bone repair were evaluated in vitro with human calvaria cells and in vivo in a rat cranial defect. Both materials exhibited specific structures, 5 mg/mL was soft with an open porous network of fibrils; 40 mg/mL was stiffer with a plugged surface and bundles of collagen fibrils. Osteoblasts seeded on 5 mg/mL formed an epithelioid layer with ultrastructural characteristics of mature osteoblasts and induced mineralization. Numerous osteoblasts migrated inside 5 mg/mL, triggering reorganization of their actin cytoskeleton, whereas on 40 mg/mL osteoblasts remained in a resting state. In rat calvaria defects, both materials induced active bone formation. Dual energy X-ray absorption bone area measures after 4 weeks averaged 84.0% with 5 mg/mL, 88.4% with 40 mg/mL, and 36.7% in the controls (p < 0.05). Tartrate resistant acid phosphatase-positive giant cells releasing amounts of metalloproteinase-2 progressively degraded the implants at 76.5% with 5 mg/mL and 38.2% with 40 mg/mL (p < 0.05), whereas alkaline phosphatase-positive osteoprogenitors invaded collagen remnant. Hence, the dense structure of collagen materials allowed cell invasion and raise their mechanical behavior without addition of chemical cross-linkers. Collagen concentration can be tuned to form 3D matrices for in vitro investigations or to fit degradation rate to different bone repair purposes. PMID- 21034314 TI - The link between hyperuricosuria and urate urolithiasis. PMID- 21034316 TI - A proposed new classification for the renal collecting system of cattle. AB - OBJECTIVE: To evaluate the intrarenal anatomy of kidneys obtained from cattle and to propose a new classification for the renal collecting system of cattle. SAMPLE POPULATION: 37 kidneys from 20 adult male mixed-breed cattle. PROCEDURES: Intrarenal anatomy was evaluated by the use of 3-D endocasts made of the kidneys. The number of renal lobes and minor renal calyces in each kidney and each renal region (cranial pole, caudal pole, and hilus) was quantified. RESULTS: The renal pelvis was evident in all casts and was classified into 2 types (nondilated [28/37 {75.7%}] or dilated [9/37 {24.3%}]). All casts had a major renal calyx associated with the cranial pole and the caudal pole. The number of minor renal calices per kidney ranged from 13 to 64 (mean, 22.7). There was a significant correlation between the number of renal lobes and the number of minor renal calices for the entire kidney, the cranial pole region, and the hilus region; however, there was not a similar significant correlation for the caudal pole region. Major and minor renal calices were extremely narrow, compared with major and minor renal calices in pigs and humans. CONCLUSIONS AND CLINICAL RELEVANCE: The renal collecting system of cattle, with a renal pelvis and 2 major renal calices connected to several minor renal calices by an infundibulum, differed substantially from the renal collecting system of pigs and humans. From a morphological standpoint, the kidneys of cattle were not suitable for use as a model in endourologic research and training. PMID- 21034317 TI - Effects of perzinfotel, butorphanol tartrate, and a butorphanol-perzinfotel combination on the minimum alveolar concentration of isoflurane in cats. AB - OBJECTIVE: To determine the effects of perzinfotel, butorphanol, and their combination on the minimal alveolar concentration (MAC) of isoflurane in cats. ANIMALS: 7 healthy sexually intact cats (4 males and 3 females), aged 12 to 17 months and weighing 2.8 to 4.6 kg. PROCEDURES: In a crossover design, saline (0.9% NaCl) solution, perzinfotel (2.5 to 15 mg/kg; IV, IM, and SC), butorphanol tartrate (0.2 mg/kg, IM), or a combination of 5 mg of perzinfotel/kg and 2 mg of butorphanol tartrate/kg (both IM) was administered to 6 cats before 7 separate episodes of anesthesia with isoflurane in oxygen. Heart rate, arterial blood pressure, bispectral index (BIS), and inspiration and expiration concentrations of isoflurane were continuously monitored. The isoflurane MAC was determined twice during anesthesia. RESULTS: IV, IM, and SC administration of perzinfotel at 2.5 to 15 mg/kg resulted in a significant decrease in mean isoflurane MAC by 43.3% to 68.0%. The BIS significantly increased after perzinfotel administration via the same routes at 2.5 to 15 mg/kg and after perzinfotel-butorphanol administration IM. Blood pressure was significantly higher after perzinfotel was administered at 5 mg/kg, IM; 10 mg/kg, IV; and 10 mg/kg, SC than after saline solution administration. CONCLUSIONS AND CLINICAL RELEVANCE: Perzinfotel administration decreased the isoflurane MAC and increased several BIS and blood pressure values in anesthetized cats. Administration of perzinfotel prior to isoflurane anesthesia may improve anesthetic safety by reducing inhalant anesthetic requirements and improving cardiovascular function during anesthesia. PMID- 21034318 TI - Pharmacokinetics of meloxicam following intravenous and oral administration in green iguanas (Iguana iguana). AB - OBJECTIVE: To determine pharmacokinetics of meloxicam in healthy green iguanas following PO and IV administration and assess potential toxicity. ANIMALS: 21 healthy green iguanas (Iguana iguana). PROCEDURES: To assess pharmacokinetics, 13 iguanas were administered a single dose (0.2 mg/kg) of meloxicam PO and, 14 days later, the same dose IV. To assess potential toxicity, 4 iguanas were given meloxicam at a dosage of 1 or 5 mg/kg, PO, every 24 hours for 12 days, and results of histologic examination were compared with results for another 4 iguanas given a single dose of meloxicam (0.2 mg/kg). RESULTS: There were no significant differences between PO and IV administration with regard to terminal half-life (mean +/- SD, 12.96 +/- 8.05 hours and 9.93 +/- 4.92 hours, respectively), mean area under the curve to the last measured concentration (5.08 +/- 1.62 MUg*h/mL and 5.83 +/- 2.49 MUg*h/mL), volume of distribution (745 +/- 475 mL/kg and 487 +/- 266 mL/kg), or clearance (40.17 +/- 10.35 mL/kg/h and 37.17 +/- 16.08 mL/kg/h). Maximum plasma concentration was significantly greater following IV (0.63 +/- 0.17 MUg/mL) versus PO (0.19 +/- 0.07 MUg/mL) administration. Time from administration to maximum plasma concentration and mean residence time were significantly longer following PO versus IV administration. Daily administration of high doses (1 or 5 mg/kg) for 12 days did not induce any histologic changes in gastric, hepatic, or renal tissues. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that administration of meloxicam at a dose of 0.2 mg/kg IV or PO in green iguanas would result in plasma concentrations > 0.1 MUg/mL for approximately 24 hours. PMID- 21034319 TI - Determination of the prevalence and severity of metacarpophalangeal joint osteoarthritis in Thoroughbred racehorses via quantitative macroscopic evaluation. AB - OBJECTIVE: To determine the prevalence and severity of osteoarthritis in the metacarpophalangeal joints of Thoroughbred racehorses via development and validation of a quantitative macroscopic evaluation system. SAMPLE POPULATION: Metacarpophalangeal joints from 50 Thoroughbred racehorses. PROCEDURES: Joints were collected from horses that died or were euthanized within 60 days of racing. Metacarpophalangeal joints were assessed for osteoarthritic degeneration by use of macroscopic and histologic scoring systems, polarized light microscopy, and cartilage biochemical analysis. The global macroscopic score for the entire metacarpophalangeal joint was based on factors that reflected the size and severity of lesions as well as the involvement of weight-bearing surfaces. RESULTS: One-third of all 2- and 3-year-old horses had partial-or full-thickness cartilage lesions and osteoarthritis. Osteoarthritis severity increased until age 6 in this population. Significant correlations were found between macroscopic grade and age, cause of death, glycosaminoglycan depletion, and loss of superficial cartilage zone polarized light intensity. CONCLUSIONS AND CLINICAL RELEVANCE: The macroscopic system devised for this study had good correlations with quantitative methods. Two-and 3-year-old horses had full-thickness cartilage lesions that may have been career limiting. Year-to-year attrition and a small population of older horses may have led to underestimation of the prevalence of osteoarthritis in older horses. The macroscopic scoring system was reliable when used by nonexpert and expert users. PMID- 21034321 TI - Quantitative contrast-enhanced ultrasonographic analysis of perfusion in the kidneys, liver, pancreas, small intestine, and mesenteric lymph nodes in healthy cats. AB - OBJECTIVE: To evaluate perfusion of abdominal organs in healthy cats by use of contrast-enhanced ultrasonography. ANIMALS: 10 young healthy anesthetized cats. PROCEDURES: Contrast-enhanced ultrasonography of the liver, left kidney, pancreas, small intestine, and mesenteric lymph nodes was performed on anesthetized cats. RESULTS: Typical perfusion patterns were found for each of the studied organs. Differences in perfusion among organs were associated with specific physiologic features. The liver was enhanced gradually and had a more heterogeneous perfusion pattern because of its dual blood supply and close proximity to the diaphragm, compared with other organs. An obvious and significant difference in perfusion was detected between the renal cortex and medulla. No significant differences in perfusion were detected among the pancreas, small intestine, and mesenteric lymph nodes. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that contrast-enhanced ultrasonography can be used in cats to estimate organ perfusion as in other species. Observed differences in perfusion variables can be mostly explained by physiologic differences in vascularity. PMID- 21034320 TI - Influence of treatment with ultralow-dose aspirin on platelet aggregation as measured by whole blood impedance aggregometry and platelet P-selectin expression in clinically normal dogs. AB - OBJECTIVE: To evaluate the influence of treatment with ultralow-dose aspirin (ULDAsp) on platelet aggregation, P-selectin (CD62P) expression, and formation of platelet-leukocyte aggregates in clinically normal dogs. ANIMALS: 18 clinically normal dogs. PROCEDURES: Studies were conducted before and 24 hours after ULDAsp administration (0.5 mg/kg, PO, q 24 h, for 2 days). Whole blood impedance aggregometry for the assessment of platelet function was performed with sodium citrate-anticoagulated blood and aggregation agonists (ADP at 20, 10, and 5 MUmol/L; collagen at 10, 5, and 2 MUg/mL). Onset, maximum response, and rate of platelet aggregation were recorded. Flow cytometric assays were configured to detect thrombin-induced CD62P expression and platelet-leukocyte aggregates in EDTA-anticoagulated whole blood. Externalized platelet CD62P and constitutive CD61 (GPIIIa) were labeled with antibodies conjugated to phycoerythrin (PE) and fluorescein isothiocyanate (FITC), respectively. Red blood cell-lysed paraformaldehyde-fixed EDTA-anticoagulated whole blood was dual labeled with CD61 FITC and a panleukocyte antibody (CD18-PE) to characterize platelet-leukocyte aggregates. RESULTS: ULDAsp significantly delayed platelet aggregation onset with ADP at 20 MUmol/L by 54% to 104%, attenuated maximum aggregation with various concentrations of ADP and collagen by >= 41%, and slowed aggregation rate with the highest ADP and collagen concentrations by >= 39%. Depending on the parameter tested, up to 30% of dogs failed to have an ULDAsp effect. Thrombin stimulation significantly increased CD62P expression in platelets and platelet-leukocyte aggregates, but ULDAsp did not alter basal or thrombin-stimulated CD62P expression. CONCLUSIONS AND CLINICAL RELEVANCE: ULDAsp treatment of clinically normal dogs impaired platelet aggregation in most dogs, but did not influence CD62P platelet membrane expression. PMID- 21034322 TI - Cyclooxygenase-2 mRNA expression in equine nonglandular and glandular gastric mucosal biopsy specimens obtained before and after induction of gastric ulceration via intermittent feed deprivation. AB - OBJECTIVE: To measure the expression of cyclooxygenase-2 (COX-2) mRNA in gastric biopsy specimens serially obtained from horses before, during, and after an 8-day intermittent feed-deprivation trial and to investigate the mucosal location of COX-2. ANIMALS: 9 mixed-breed horses for retrieval of gastric biopsy specimens and 16 additional horses for immunohistochemical analysis. PROCEDURES: Gastric biopsy specimens were obtained from 6 horses; 3 of these horses and 3 more participated in an intermittent feed-deprivation trial 9 weeks later. A quantitative PCR assay was used to determine the amount of COX-2 mRNA in biopsy specimens from nonulcerated and ulcerated gastric mucosa. Immunohistochemical staining of specimens by use of a polyclonal anti-COX-2 antibody was performed on full-thickness postmortem gastric biopsy specimens. RESULTS: COX-2 mRNA was expressed in all glandular gastric mucosal specimens but was only detectable in nonglandular mucosal specimens when ulceration was present or during ulcer healing. Positive staining for COX-2 was present in 12 of 14 nonulcerated glandular mucosal sections. Although such staining was weak or absent in nonulcerated nonglandular sections, stronger staining was evident in regenerating epithelium at the rims of erosions and ulcers. CONCLUSIONS AND CLINICAL RELEVANCE: COX-2 was constitutively present in equine glandular gastric mucosa, although its contribution to mucosal protection remains unclear. Our finding of COX-2 mRNA expression in ulcer margins during healing may support a role for the products of this enzyme in mucosal repair. The potential roles of COX-2 should be considered when COX-2-selective inhibitors are prescribed for horses with gastric ulcers. PMID- 21034323 TI - Use of geospatial neighborhood control locations for epidemiological analysis of community-level pet adoption patterns. AB - OBJECTIVE: To explore the joint effect of distance and neighborhood-level demographics on pet adoptions from an animal shelter by means of client segmentation, geospatial tools, and epidemiological techniques. SAMPLE POPULATION: Geocoded locations of 1,563 adoptions from an animal shelter in eastern Massachusetts and 4,700 geospatial control locations. PROCEDURES: Pet adoptions were geocoded to addresses by use of spatial analysis software for area based analysis. A population of neighborhood control locations (proportional to human population at the level of the block group) was randomly generated. Adoption and control locations were spatially joined to census data and to defined lifestyle segments. The association of geodemographic variables with adoption was assessed by use of multivariate logistic regression. RESULTS: The shelter service area was not well described by individual geopolitical boundaries such as county. Locations that were < 9.7 km (6 miles) from the shelter, had higher block group median income, or had a greater proportion of households that were composed of married couples with children in the block group were associated with increased odds of being an adoption location. Neighborhood lifestyle characteristics affected the association between affluence and adoption. Controlling for distance of a location to the shelter markedly affected the strength of association with adoption. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that distance as well as neighborhood lifestyle characteristics profoundly influences shelter adoption patterns. Client segmentation and geodemographic analysis can reveal communities with increased likelihood of pet adoption from a shelter and help clarify adoption patterns. PMID- 21034325 TI - Longitudinal prevalence and molecular typing of Escherichia coli O157:H7 by use of multiple-locus variable-number tandem-repeat analysis and pulsed-field gel electrophoresis in fecal samples collected from a range-based herd of beef cattle in California. AB - OBJECTIVE: To evaluate seasonal patterns and risk factors for Escherichia coli O157:H7 in feces in a beef cattle herd and determine strain diversity and transition in E coli over time by use of multiple-locus variable-number tandem repeat analysis (MLVA) and pulsed-field gel electrophoresis (PFGE). SAMPLE POPULATION: 456 samples of freshly passed feces collected over a 1-year period from cattle in a range-based cow-calf operation located in the foothills of the Sierra Nevada Mountains in California. PROCEDURES: E coli O157:H7 was recovered from feces by use of immunomagnetic separation and 2 selective media. Virulence factors were detected via reverse transcriptase-PCR assay. Escherichia coli O157:H7 isolates were subtyped with MLVA and PFGE. Prevalence estimates were calculated and significant risk factors determined. A dendrogram was constructed on the basis of results of MLVA typing. RESULTS: Overall prevalence estimate for E coli O157:H7 was 10.5%, with the prevalence lowest during the winter. Mean temperature during the 30 days before collection of samples was significantly associated with prevalence of E coli O157:H7 in feces. Nineteen MLVA and 12 PFGE types were identified. CONCLUSIONS AND CLINICAL RELEVANCE: A seasonal pattern was detected for prevalence of E coli O157:H7 in feces collected from beef cattle in California. Subtyping via MLVA and PFGE revealed a diversity of E coli O157:H7 strains in a cow-calf operation and noteworthy turnover of predominant types. Given the importance of accurately determining sources of contamination in investigations of disease outbreaks in humans, MLVA combined with PFGE should be powerful tools for epidemiologists. PMID- 21034324 TI - Effects of rosiglitazone, an agonist of the peroxisome proliferator-activated receptor gamma, on intestinal damage induced by Escherichia coli lipopolysaccharide in weaned pigs. AB - OBJECTIVE: To determine whether rosiglitazone, an agonist of the peroxisome proliferator-activated receptor (PPAR) gamma, could alleviate intestinal damage induced by Escherichia coli lipopolysaccharide (LPS) in weaned pigs. ANIMALS: 18 weaned pigs (mean +/- SD age, 28 +/- 3 days). PROCEDURES: Pigs were allocated to 3 treatments (6 pigs/treatment). Control pigs were injected IP with dimethyl sulfoxide and then injected 30 minutes later with sterile saline (0.9% NaCl) solution, LPS-treated pigs were injected IP with dimethyl sulfoxide and then injected 30 minutes later with LPS (100 MUg/kg, IP), and rosiglitazone plus LPS treated pigs were injected with rosiglitazone (3 mg/kg, IP) and then injected 30 minutes later with LPS (100 MUg/kg, IP). Pigs were euthanized 3 hours after challenge exposure, and samples of the small intestines were collected for histologic, biochemical, and immunohistochemical examination. RESULTS: Rosiglitazone alleviated LPS-induced intestinal damage, which was manifested as a lower crypt depth in the duodenum and a higher villus height-to-crypt depth ratio in the duodenum, jejunum, and ileum. Rosiglitazone also mitigated inhibition of crypt cell proliferation in the jejunum and ileum induced by LPS injection. Pretreatment with rosiglitazone significantly increased the number of cells that stained for PPARgamma and significantly decreased the number of cells that stained for inducible nitric oxide synthase. CONCLUSIONS AND CLINICAL RELEVANCE: Rosiglitazone alleviated intestinal damage induced by LPS injection in weaned pigs. The protective effects of rosiglitazone on the intestines may be associated with inhibition of intestinal proinflammatory mediators, such as inducible nitric oxide synthase. PMID- 21034326 TI - Evaluation of the effect of pelvic tilt in the coronal plane on the Norberg angle measured in ventrodorsal radiographic views of a canine hip joint bone model. AB - OBJECTIVE: To determine the effect of pelvic tilt on the Norberg angle (NA) measured in ventrodorsal radiographic views of a hip joint in a canine femoral pelvic bone model. SAMPLE POPULATION: Radiographic views of a femoral-pelvic bone model with 1 articulated hip joint (without evident laxity). PROCEDURES: The bone model was placed on a radiography table. With the joint fully extended, the pelvic coronal plane was tilted from 0 degrees in 5 degrees increments caudally and cranially to a maximum of 30 degrees in each direction (femoral frontal plane was maintained parallel with the radiograph cassette); a digital ventrodorsal radiographic view was obtained at each tilt position. In each image, the NA was measured 3 times by 2 observers (operators). The effect of pelvic tilt on the NA was evaluated by use of a repeated-measures analysis; within-and between-operator variances were also assessed. RESULTS: Within-operator repeatability was excellent for assessments of hip joint NAs in radiographic views obtained when cranial or caudal tilt was applied to the femoral-pelvic model; replicate measurement variation was < 2.5% (coefficient of variation < 5%). Mean NA values determined by the 2 operators in cranial or caudal tilt views did not differ. Mean between-operator difference in caudal tilt measurements was 0.55 degrees (95% confidence interval, -1.69 degrees to 0.59 degrees ) and in cranial tilt measurements was -0.13 degrees (95% confidence interval, -1.33 degrees to 1.06 degrees ). Cranial or caudal pelvic tilt did not affect measurement of the NA. CONCLUSIONS AND CLINICAL RELEVANCE: Model-derived results indicated that pelvic tilt during acquisition of ventrodorsal radiographic views of the hip joints of a dog should not affect measurement of the NA. PMID- 21034327 TI - Evaluation of 12- and 24-month survival rates after treatment with masitinib in dogs with nonresectable mast cell tumors. AB - OBJECTIVE: To evaluate the effectiveness of masitinib for the treatment of nonresectable mast cell tumors (MCTs) in dogs at 12 and 24 months after onset of treatment. ANIMALS: 132 dogs with nonresectable grade 2 or 3 MCTs. PROCEDURES: Dogs received masitinib (12.5 mg/kg/d, PO; n = 106) or a placebo (26). After 6 months, treatment was extended with tumor assessments at 3-month intervals until detection of disease progression. Endpoints were tumor response and overall survival rate and time. RESULTS: In dogs with nonresectable MCTs, masitinib significantly improved survival rate, compared with results for the placebo, with 59 of 95 (62.1%) and 9 of 25 (36.0%) dogs alive at 12 months and 33 of 83 (39.8%) and 3 of 20 (15.0%) dogs alive at 24 months, respectively. Median overall survival time was 617 and 322 days, respectively. Tumor control at 6 months had a high predictive value for 24-month survival, with high specificity (88%) and sensitivity (76%), whereas short-term tumor response (within 6 weeks) had a poor predictive value. Complete responses at 24 months were observed in 6 of 67 (9.0%) dogs with nonresectable MCTs treated with masitinib. CONCLUSIONS AND CLINICAL RELEVANCE: Masitinib significantly increased survival rates at 12 and 24 months in dogs with nonresectable MCTs. Control of disease at 6 months, but not best response at 6 weeks, was predictive of long-term survival in dogs treated with masitinib, which suggested that short-term response may be irrelevant for assessing clinical efficacy of tyrosine kinase inhibitors for treatment of MCTs. PMID- 21034328 TI - Effects of lycopene on proliferation and death of canine osteosarcoma cells. AB - OBJECTIVE: To determine the effects of lycopene with and without concurrent chemotherapeutic treatment on growth and apoptosis of canine osteosarcoma cells. SAMPLE POPULATION: Cell cultures of 3 established canine osteosarcoma cell lines (D17, OS 2.4, and HMPOS). PROCEDURES: Growth curve kinetics and cell cytotoxicosis for various treatment combinations were assessed by use of 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Additionally, cell cycle kinetics and colony-forming soft agar assays were performed to determine the influences of lycopene on the cell cycle and anchorage-independent growth. Western immunoblotting of HMPOS cells was performed to examine signaling and apoptotic pathways implicated in lycopene-induced apoptosis. RESULTS: Lycopene alone caused mild to pronounced attenuation of cell proliferation of all 3 cell lines as well as apoptosis in HMPOS cells but did not interfere with cell death in response to doxorubicin. Soft agar anchorage-independent growth assays revealed complete inhibition of cell proliferation in 2 of 3 osteosarcoma cell lines. Further investigation into the apoptotic response revealed activation of mitochondrial-induced apoptosis primarily through expression of truncated Bid and a decrease in protein kinase B (ie, AKT) phosphorylation. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that lycopene may be beneficial during treatment of osteosarcomas. Lycopene did not negatively or positively affect survival of osteosarcoma cells during doxorubicin treatment and independently induced apoptosis in the HMPOS cell line. These findings warrant further in vitro and in vivo studies into the use of this natural compound as an adjuvant antiproliferative, proapoptotic treatment in dogs with osteosarcoma. PMID- 21034329 TI - Pharmacokinetics of gallium maltolate after intragastric administration in adult horses. AB - OBJECTIVE: To determine the pharmacokinetics of gallium maltolate (GaM) after intragastric administration in adult horses. ANIMALS: 6 adult horses. PROCEDURES: Feed was withheld for 12 hours prior to intragastric administration of GaM (20 mg/kg). A single dose of GaM was administered to each horse via a nasogastric tube (time 0). Blood samples were collected at various time points from 0 to 120 hours. Serum was used to determine gallium concentrations by use of inductively coupled plasma-mass spectroscopy. Noncompartmental and compartmental analyses of serum gallium concentrations were performed. Pharmacokinetic models were selected on the basis of the Akaike information criterion and visual analysis of plots of residuals. RESULTS: Serum concentration data for 1 horse were such that this horse was considered an outlier and excluded from noncompartmental and compartmental analyses. Noncompartmental analysis was used to determine individual pharmacokinetic parameters. A 1-compartment model with first-order input and output and lag time was selected as the best-fit model for the data and used to determine mean +/- SD values for maximum observed serum concentration (0.28 +/- 0.09 MUg/mL), time of maximum concentration (3.09 +/- 0.43 hours), time to the first measurable concentration (0.26 +/- 0.11 hours), apparent elimination half-life (48.82 +/- 5.63 hours), area under the time-concentration curve (20.68 +/- 757 h*MUg/mL), and apparent volume of distribution (73,493 +/- 18,899 mL/kg). CONCLUSION AND CLINICAL RELEVANCE: Further studies are necessary to determine the bioavailability of GaM after intragastric administration in adult horses. PMID- 21034330 TI - Pharmacokinetics of orally administered DL-alpha-lipoic acid in dogs. AB - OBJECTIVE: To determine the pharmacokinetics of DL-alpha-lipoic acid in dogs when administered at 3 dosages via 3 methods of delivery. ANIMALS: 27 clinically normal Beagles. PROCEDURES: In a 3 * 3 factorial Latin square design, 3 dosages (2.5, 12.5, and 25 mg/kg) of DL-alpha-lipoic acid were administered orally in a capsule form and provided without a meal, in a capsule form and provided with a meal, and as an ingredient included in an extruded dog food. Food was withheld for 12 hours prior to DL-alpha-lipoic acid administration. Blood samples were collected before (0 minutes) and at 15, 30, 45, 60, and 120 minutes after administration. Plasma concentrations of DL-alpha-lipoic acid were determined via high-performance liquid chromatography. A generalized linear models procedure was used to evaluate the effects of method of delivery and dosage. Noncompartmental analysis was used to determine pharmacokinetic parameters of DL-alpha-lipoic acid. Nonparametric tests were used to detect significant differences between pharmacokinetic parameters among treatment groups. RESULTS: A significant effect of dosage was observed regardless of delivery method. Method of delivery also significantly affected plasma concentrations of DL-alpha-lipoic acid, with extruded foods resulting in lowest concentration for each dosage administered. Maximum plasma concentration was significantly affected by method of delivery at each dosage administered. Other significant changes in pharmacokinetic parameters were variable and dependent on dosage and method of delivery. CONCLUSIONS AND CLINICAL RELEVANCE: Values for pharmacokinetic parameters of orally administered DL-alpha-lipoic acid may differ significantly when there are changes in dosage, method of administration, and fed status. PMID- 21034332 TI - Evaluation of fluid pressures of common wound-flushing techniques. AB - OBJECTIVE: To evaluate fluid pressures generated via common wound-flushing techniques. SAMPLE POPULATION: 24 combinations of bottles, needles, a syringe, and a bag. PROCEDURES: 12 medically trained individuals used the following devices to forcefully expel fluid as for wound flushing: full and half-full 1-L and 500-mL bottles with holes in the cap made with 16-, 18-, 20-, and 22-gauge needles; a 35-mL syringe with the same needle sizes; and a 1-L bag placed in a cuff pressurized to 300 mm Hg, with the same needle sizes. Fluid expulsion pressures were measured and compared. RESULTS: The highest pressure generated with the bottle was 3.90 +/- 1.30 psi (mean +/- SD) with a 16-gauge needle and a full 1-L bottle. The highest pressure generated with the 35-mL syringe was 18.40 +/- 9.80 psi with a 16-gauge needle. The lowest pressure generated with the 35-mL syringe was 16.70 +/- 6.50 psi with an 18-gauge needle. The bag under pressure generated a pressure of 7.3 +/- 0.1 psi with a 16-gauge needle. Needle size did not have a significant effect. CONCLUSIONS AND CLINICAL RELEVANCE: Solution bottles of any size and needle gauge do not meet the requirement for satisfactory flushing pressure of 7 to 8 psi. Use of a 35-mL syringe can produce pressure substantially > 7 to 8 psi, which could damage tissues. The most consistent delivery method to generate 7 to 8 psi was use of a 1-L plastic bag within a cuff pressurized to 300 mm Hg. PMID- 21034333 TI - Influence of kidney function on urinary excretion of albumin and retinol-binding protein in dogs with naturally occurring renal disease. AB - OBJECTIVE: To evaluate excretion of urinary albumin (UAlb) and urinary retinol binding protein (URBP) in dogs with naturally occurring renal disease. ANIMALS: 64 client-owned dogs. PROCEDURES: Dogs were assigned to groups according to plasma creatinine concentration, urinary protein-to-urinary creatinine ratio (UP:UC), and exogenous plasma creatinine clearance (P-Cl(Cr)) rates: group A (n = 8), nonazotemic (plasma creatinine < 125 MUmol/L) and nonproteinuric (UP:UC < 0.2) with P-Cl(Cr) rate > 90 mL/min/m2; group B (26), nonazotemic and nonproteinuric with P-Cl(Cr) rate 50 to 89 mL/min/m2; group C (7), nonazotemic but proteinuric with P-Cl(Cr) rate 53 to 98 mL/min/m2; group D (8), azotemic and borderline proteinuric with P-Cl(Cr) rate 22 to 45 mL/min/m2); and group E (15), azotemic and proteinuric (P-Cl(Cr) not evaluated). The UAlb and URBP concentrations were measured via ELISA; UAlb-to-urinary creatinine (UAlb:UC) and URBP-to-urinary creatinine (URBP:UC) ratios were determined. RESULTS: UAlb:UC and URBP:UC did not differ between groups A and B. Increased UAlb: UCs and URBP:UCs were paralleled by increased UP:UCs in groups C, D, and E relative to values from groups A and B, independent of azotemia. There were significant positive correlations of UP:UC with UAlb:UC and of UAlb:UC with URBP:UC (r = 0.82 and 0.46, respectively). However, UP:UC, UAlb:UC, and URBP:UC were not significantly correlated with P-ClCr rate. CONCLUSIONS AND CLINICAL RELEVANCE: UAlb and URBP concentrations were paralleled by urinary protein concentrations and may be useful in assessing renal management of plasma proteins. Determination of urinary protein, UAlb, or URBP concentration was not sufficiently sensitive to detect reduced P-Cl(Cr) in nonazotemic dogs. PMID- 21034335 TI - Creating the cat-friendly practice. PMID- 21034336 TI - Postoperative pain management with incisional local anesthetic infiltration. PMID- 21034337 TI - Humane issues surrounding decapitation reconsidered. PMID- 21034338 TI - What is your diagnosis? Intestinal foreign body. PMID- 21034339 TI - What is your diagnosis? Plasma cell neoplasia. PMID- 21034340 TI - Diagnostic imaging in veterinary dental practice. Oral carcinoma. PMID- 21034341 TI - Pathology in practice. Pemphigus foliaceous. PMID- 21034342 TI - ECG of the Month. Respiratory sinus arrhythmia. PMID- 21034343 TI - Brachycephalic airway obstructive syndrome in dogs: 90 cases (1991-2008). AB - OBJECTIVE: To determine the prevalence of individual anatomic components of brachycephalic airway obstructive syndrome (BAOS), including everted tonsils, and analyze the frequency with which each component occurs with 1 or more other components of BAOS in brachycephalic dogs. DESIGN: Retrospective case series. ANIMALS: 90 dogs with BAOS. PROCEDURES: Medical records were reviewed for signalment, clinical signs at time of admission, historical and physical examination findings, BAOS components found on laryngoscopic examination of the pharynx and larynx, surgical procedures performed, and perioperative complications. RESULTS: English Bulldogs (55/90 [61%]), Pugs (19/90 [21%]), and Boston Terriers (8/90 [9%]) were the most common breeds with BAOS. The most common components of BAOS were elongated soft palate (85/90 [94%]), stenotic nares (69/90 [77%]), everted laryngeal saccules (59/90 [66%]), and everted tonsils (50/90 [56%]). Dogs most commonly had 3 or 4 components of BAOS, with the most common combination being stenotic nares, elongated soft palate, everted laryngeal saccules, and everted tonsils. Dogs with stenotic nares were significantly more likely to have everted laryngeal saccules (50/69 [72%]), and dogs with everted laryngeal saccules were significantly more likely to have everted tonsils (39/59 [66%]). Postoperative surgical complications occurred in 12% (10/83) of dogs that received corrective surgery. No specific BAOS component made dogs more likely to have complications. CONCLUSIONS AND CLINICAL RELEVANCE: The prevalence of components of BAOS in brachycephalic dogs of this study differed from that reported previously, especially for everted tonsils. Thorough examination of the pharynx and larynx is necessary for detection of BAOS components. PMID- 21034344 TI - Response rate after administration of a single dose of doxorubicin in dogs with B cell or T-cell lymphoma: 41 cases (2006-2008). AB - OBJECTIVE: To determine the response rate after administration of a single dose of doxorubicin in dogs with B-cell or T-cell multicentric or thymic lymphoma. DESIGN: Retrospective case series. ANIMALS: 41 client-owned dogs with lymphoma. PROCEDURES: Medical records of dogs in which lymphoma was diagnosed between February 2006 and October 2008 were reviewed. Entry criteria included that dogs had a confirmed lymphoma that was immunophenotyped to be of B-cell or T-cell origin. Only dogs that received doxorubicin alone as their first chemotherapy treatment and were evaluated 1 week later were included in the study. Dogs were excluded when they had received prior treatment with corticosteroids. Medical records were reviewed to obtain signalment, stage and substage of lymphoma, and immunophenotype and to determine whether the dog had hypercalcemia at the time of diagnosis. RESULTS: Dogs with T-cell lymphoma had a significantly lower response rate to doxorubicin than did dogs with B-cell lymphoma. Twenty-five of 29 (86.2%) dogs with B-cell lymphoma had a complete response, compared with 2 of 12 dogs in the T-cell group that had a complete response. The overall response rate of dogs with B-cell lymphoma was 100%, compared with a response rate of 50% in dogs with T-cell lymphoma. CONCLUSIONS AND CLINICAL RELEVANCE: Standard-of-care chemotherapy protocols for the treatment of dogs with lymphoma include doxorubicin. Many dogs with T-cell lymphoma did not respond to doxorubicin; therefore, multiagent protocols containing doxorubicin may not be optimal. Alternative protocols should be considered for dogs with T-cell lymphoma that do not respond to doxorubicin. PMID- 21034345 TI - Panniculitis attributable to Mycobacterium goodii in an immunocompetent dog in Georgia. AB - CASE DESCRIPTION: A 5-year-old 38.3-kg (84.5-lb) mixed-breed dog was examined because of acute onset of lethargy and anorexia. Four days later, a raised, firm, warm 15 * 10-cm lesion was detected in the right caudal paralumbar area. CLINICAL FINDINGS: Cephalexin treatment yielded a poor response. Formalin-fixed tissue and fluid samples from the cystic areas of the lesion were submitted for cytologic and histologic examinations, routine bacterial and mycobacterial culture, and genus identification and 16S partial sequencing via PCR assays. Cytologic examination revealed chronic pyogranulomatous inflammation. Histologic examination by use of routine, Giemsa, silver, acid-fast, and modified acid-fast stains revealed multifocal nodular granulomatous panniculitis without identifiable organisms. Mycobacteria were initially identified via PCR assay and mycobacterial culture within 3 days. Mycobaterium goodii was speciated by use of partial 16S RNA sequence analysis. TREATMENT AND OUTCOME: The lesion resolved after long-term treatment with a combination of rifampin and clarithromycin and insertion of a Penrose drain. There has been no recurrence of the condition. CLINICAL RELEVANCE: M goodii is an environmental rapidly growing mycobacterium and is a zoonotic pathogen. Infections have not been previously reported in domestic animals in North America, although there are rare reports of infection in humans associated with surgery, especially surgical implants. Domestic animals are a potential sentinel for this non-tuberculous mycobacterial infection in humans, although lack of speciation in infections of domestic animals likely underestimates the potential public health importance of this pathogenic organism. Current microbiological molecular methods allow for a rapid and inexpensive diagnosis. PMID- 21034346 TI - Comparison of complications and long-term survival rates following hand-sewn versus stapled side-to-side jejunocecostomy in horses with colic. AB - OBJECTIVE: To evaluate survival rate and complications after jejunocecostomy in horses with colic and to compare outcomes after hand-sewn versus stapled side-to side jejunocecostomy. DESIGN: Retrospective cohort study. ANIMALS: 32 horses. PROCEDURES: Information was retrieved from medical records and through telephone calls on horses that had a hand-sewn or stapled side-to-side jejunocecostomy for treatment of colic, which was performed by or under the supervision of the same surgeon. Kaplan-Meier life table analysis was used to compare survival times and rates between horses that underwent a hand-sewn or stapled side-to-side anastomosis. RESULTS: 32 horses met inclusion criteria; 22 underwent a hand-sewn anastomosis, and 10 underwent a stapled anastomosis. Horses in the stapled group had a significantly greater prevalence of postoperative colic and combined postoperative colic and reflux than horses in the hand-sewn group. In the hand sewn group, repeated celiotomy was performed within the same hospitalization period for 3 of 22 horses; in the stapled group, 4 of 10 horses had repeated celiotomies. Hospital discharge rates (ie, short-term survival rates) were similar between horses in the hand-sewn group (20/22 horses) and those in the stapled group (9/10 horses). Long-term survival rates were similar for both groups, ranging from 5 to 126 months. CONCLUSIONS AND CLINICAL RELEVANCE: Short- and long-term results justify use of jejunocecostomy in horses. Despite similar survival rates between groups, horses that underwent a stapled anastomosis had significantly greater prevalences of postoperative complications than horses that underwent a hand-sewn anastomosis, suggesting that horses were sensitive to minor differences in anastomosis techniques. PMID- 21034347 TI - Repeated testing by use of culture and PCR assay to detect Tritrichomonas foetus carrier bulls in an infected Nebraska herd. AB - OBJECTIVE: To compare methods for identification of bulls that were carriers for Tritrichomonas foetus during an outbreak on a large beef ranch and determine whether the percentage of nonpregnant cows was associated with the percentage of bulls infected with T foetus. DESIGN: Epidemiological study. ANIMALS: 121 Angus and Hereford bulls (1.5 to 6 years old) and 2,960 Angus-cross cows (2.5 to 14 years old) managed as 5 herds on a Nebraska beef ranch. PROCEDURES: 3 sequential preputial scrapings collected from the bulls at 12- to 27-day intervals were cultured, and cultures were examined for live T foetus daily for 5 days. On day 5, aliquots of the culture fluid were tested by means of T foetus-specific gel and real-time PCR assays. Cows were tested for pregnancy by means of rectal palpation. RESULTS: For 361 preputial scrapings obtained from 121 bulls, results of culture and gel PCR assay were in close agreement. The real-time PCR assay had similar sensitivity to culture and the gel PCR assay but generated more false positive results. Twenty-four of the 121 (19.8%) bulls were identified as infected with T foetus. For the 5 ranch herds, there was a positive linear correlation between percentage of infected bulls (range, 0% to 40%) and percentage of nonpregnant cows (range, 8.3% to 19.2%). CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that a combination of culture and the gel PCR assay performed on 3 sequential preputial scrapings was the best method for identifying bulls that were carriers for T foetus during this herd outbreak. PMID- 21034348 TI - Age-dependency of galactose elimination capacity in healthy children and children with chronic liver disease. AB - OBJECTIVE: Galactose elimination capacity (GEC) is used as a quantitative measure of liver metabolic function with prognostic value in adults with acute and chronic liver failure. Almost no data are available regarding GEC in children, however. This study thus aims to meet the previously unmet clinical need for age related data on GEC in children. MATERIAL AND METHODS: We studied galactose elimination in 10 healthy children (median age 10.7 years; range 7 months to 16 years) and 30 children with chronic liver disease (median age 8.6 years; range 3 months to 16 years). GEC was estimated from the linear decrease in concentration of galactose in arterialized capillary blood from the ear following intravenous infusion of galactose. RESULTS: In both groups of children, GEC (MUmol/min/kg body weight) was highest in the youngest children and decreased with age, although at a significantly lower level in the children with liver disease (p = 0.05). GEC was significantly higher in healthy children than in healthy adults, diminishing to the adult level by the age of 16 years. CONCLUSIONS: GEC was found to be higher in children than in adults until the age of 16 years. Moreover, GEC was significantly lower in children with chronic liver disease than in healthy children, underlining that GEC testing also has potential clinical usefulness as a quantitative measure of liver metabolic function in children. PMID- 21034349 TI - Flash pulmonary edema in patients with renal artery stenosis--the Pickering Syndrome. AB - AIM: We report the prevalence of flash pulmonary edema in patients consecutively referred for balloon angioplasty of uni- or bilateral renal artery stenosis (PTRA), and describe the characteristics of this special fraction of the patients. We further report two unusual cases. METHODS AND MATERIAL: Review of medical records from 60 patients consecutively referred for uni- or bilateral PTRA from 2004-2005 in Copenhagen County. RESULTS: Eight out of 60 patients had one or more episodes of flash pulmonary edema before PTRA. Compared with the remaining patients, they had a higher prevalence of bilateral stenosis (50% vs 27%) and coronary artery disease (75% vs 28%). However, only one of eight had severe systolic dysfunction of the left ventricle. After PTRA, two recurrences of flash pulmonary edema were observed. One was caused by severe restenosis and did not recur after aorto-renal bypass surgery. The other one was caused by rapid atrial fibrillation and did not recur after pacemaker and medical treatment. CONCLUSION: Flash pulmonary edema can be observed in patients with unilateral as well as bilateral stenosis. The prognosis is usually excellent upon treatment of the stenoses. Recurrences are rare unless restenosis occurs, and therefore, regular control, e.g. by Doppler-ultrasound examination is recommended. PMID- 21034350 TI - Comparison of atrial electromechanical coupling interval and P-wave dispersion in non-dipper versus dipper hypertensive subjects. AB - BACKGROUND: The lack of nocturnal BP fall less than 10% of the daytime, called non-dipper hypertension, is associated with increased cardiovascular morbidity and mortality. The aim of our study was to investigate atrial conduction time in patients with non-dipper hypertension using electromechanical coupling interval and P-wave dispersion (PWD), measured with the surface electrocardiogram and tissue Doppler echocardiographic imaging (TDI). METHODS: Age- and sex-matched 43 dipper hypertensive patients (19 male, 24 female, mean age: 53.9 +/- 10.5 years), 40 non-dipper patients (18 male, 22 female, mean age 54.3 +/- 9.6 years) and 46 healthy subjects (22 male, 24 female, mean age: 52.8 +/- 9.6 years) were included in the study. The difference between the maximum and minimum P-wave durations was calculated and defined as PWD. Atrial electromechanical coupling (PA), inter atrial and intra-atrial electromechanical delays were measured with TDI. RESULTS: PWD was significantly higher in patients with non-dippers compared with dippers (p <0.02) and controls (p <0.001). The inter-atrial conduction time was delayed in non-dippers compared with dippers (p <0.01) and controls (p <0.001). There was a positive correlation between left atrial (LA) diameter and inter-atrial conduction times (r = 0.46, p <0.001). LA diameter was also correlated with PWD (r = 0.44, p <0.001). CONCLUSION: The patients with non-dipper hypertension have higher P-wave duration, PWD and delayed inter-atrial electromechanical coupling intervals compared with those of dippers and controls. This indicates that these subjects may be more prone to atrial rhythm disturbances. PMID- 21034351 TI - Urinary monocyte chemoattractant protein-1 excretion in children with glomerular proteinuria. AB - OBJECTIVE: The aim of the study was to examine the urinary levels and clinical significance of monocyte chemoattractant protein-1 (uMCP-1) in children according to histological diagnosis and degree of proteinuria. MATERIAL AND METHODS: Group I comprised 20 children with idiopathic nephrotic syndrome (INS), examined twice (A, during INS relapse; and B, after proteinuria subsided). Group II comprised 17 children with persistent proteinuria due to focal segmental glomerulosclerosis (FSGS). Group III included 12 children with immunoglobulin A nephropathy (IgAN). The control group (C) contained 22 healthy children. uMCP-1 was determined by enzyme-linked immunosorbent assay and expressed in pg/ml. RESULTS: The median uMCP-1/creatinine ratio (uMCP-1/cr) in children with minimal change disease in relapse (IA) was significantly higher than in controls (p < 0.05), but when controlling for cyclosporine A (CsA) treatment the median uMCP-1 in children with INS, who were not treated with CsA, was 12.01 pg/mg cr (range 1.82-261.56 pg/mg cr) and did not differ from healthy controls. In examination IB the uMCP-1/cr concentration decreased and did not differ from healthy controls (p > 0.05). Children from groups II and III also had higher uMCP-1/cr levels than groups I and C (p < 0.01). uMCP-1/cr positively correlated with serum total cholesterol, low-density lipoprotein and protein/creatinine ratio in relapse (IA), and with serum cholesterol level in group B. A positive correlation between uMCP-1/cr and protein/creatinine ratio was also confirmed in groups II and III. CONCLUSION: Increased uMCP-1 was found in children with IgAN and FSGS correlated with proteinuria. A slight increase in uMCP-1 in children with INS was probably associated with CsA treatment. PMID- 21034352 TI - Diagnostic biomarkers of prostate cancer. AB - OBJECTIVE: Diagnostic tissue biomarkers for prostate cancer (PC) include basal cell markers and alpha-methylacyl-coenzyme A-racemase (AMACR), often used in combination. Their sensitivity and specificity are not perfect and there is a need for additional diagnostic biomarkers for PC in cases that are difficult to diagnose on routine stained sections. MATERIAL AND METHODS: This study investigated the diagnostic accuracy of three novel tissue biomarkers for PC found through a search in the Human Protein Atlas database ( www.proteinatlas.com ): somatic cytochrome c (CYCS), intestinal cell kinase (ICK) and inhibitor of nuclear factor-kappaB kinase subunit beta (IKBKB), and compared the results with AMACR. A tissue microarray was constructed from 40 consecutive radical prostatectomy (RP) specimens including benign prostatic tissue, atrophy, high grade prostatic intraepithelial neoplasia (HGPIN) and PC. Immunoreactivity was scored based on staining intensity and extent. Real-time polymerase chain reaction (PCR) was performed on malignant and benign frozen tissue samples from 32 RP specimens. RESULTS: All four biomarkers showed a stronger expression in PC and HGPIN than in benign tissue (p < 0.001). The highest diagnostic accuracy for PC was achieved with ICK and AMACR at 97%. The area under the curve for CYCS, ICK, IKBKB and AMACR was 0.859, 0.997, 0.865 and 0.983, respectively. The presence of mRNA transcripts of the genes was confirmed by real-time PCR in benign and malignant prostatic tissue. CONCLUSIONS: AMACR is an accurate diagnostic tissue marker for PC. However, in some PCs AMACR is false negative and a panel of CYCS, ICK and IKBKB may serve as ancillary diagnostic tool. PMID- 21034353 TI - Comparative study of two techniques used in distal hypospadias repair: tubularized incised plate (Snodgrass) and tubularized urethral plate (Duplay). AB - OBJECTIVE: The aim of this study was to compare the results of the tubularized incised plate (the Snodgrass technique) and tubularized urethral plate (the Duplay technique) in distal hypospadias repair. MATERIAL AND METHODS: Between April 2000 and September 2008, 245 distal hypospadias was corrected by a single surgeon: 132 patients underwent repair by tubularized incised plate and 113 by tubularized urethral plate. The age of the patients ranged from 16 to 48 months (mean 27 months). RESULTS: Mean follow-up was 84 months (21-120 months). With the tubularized incised plate, the meatus was vertically oriented and expanded to the apex of the glans, and the rate of fistulae formation was low (3%) but that of neourethral stenosis was high (22%). The Duplay technique led to fistulae in nine patients (8%) and stenoses in only eight (7%). CONCLUSIONS: The tubularized incised plate gave an excellent cosmetic result with fewer fistulae; however, more stenoses occurred than with the tubularized urethral plate technique. PMID- 21034355 TI - A limited sampling strategy for estimation of the area under the curve (0 to 8 hours) of mycophenolic acid administered three times daily to liver transplant recipients. AB - OBJECTIVES: Gastrointestinal side-effects caused by mycophenolic acid (MPA) are frequent in liver transplant recipients, and in these cases a switch from two to three daily doses is usually recommended. However, a limited sampling strategy for the estimation of MPA area under the curve from 0 to 8 hours (AUC(0-8h)) has not been made. DESIGN AND METHODS: In 22 liver transplant patients who were administered MPA three times daily, the trapezoidal extrapolated MPA AUC(0-8h) values using a sampling time from 0 to 2 hours were calculated. RESULTS: A tentative therapeutic range for MPA AUC(0-8h) of about 20-40 MUg.h/mL is proposed, and in the 13 patients with supratherapeutic values the total leukocyte blood count was significantly lower than in the 9 patients with AUC(0-8h) <= 40 MUg.h/mL (P < 0.001). Significant negative correlations were found between the total leukocyte blood count and the MPA trough levels (r = -0.458; P < 0.05), AUC(0-8h) (r = -0.479; P < 0.05), and AUC(0-2h) (r = -0.437; P < 0.05). A significant correlation was found between the trapezoidal extrapolated AUC(0-8h) and trapezoidal AUC(0-2h) results (r = 0.850; P < 0.001). CONCLUSIONS: The trapezoidal extrapolated AUC(0-8h), and possibly trapezoidal AUC(0-2h), may be useful for routine therapeutic MPA monitoring in liver transplant recipients in which the dosing frequency is increased from twice to three times a day. PMID- 21034356 TI - Re-evaluation of superoxide scavenging capacity of xanthohumol. AB - The chemopreventive chalcone xanthohumol (Xh) has been reported to decrease xanthine oxidase (XOD) catalysed formation of formazan from nitroblue tetrazolium (NBT) and is discussed as a potent scavenger of superoxide. Re-evaluation of the scavenging capacity indicated that Xh disturbed detection of superoxide with NBT, in case of an insufficient NBT/Xh ratio. Xh lacked superoxide scavenging activity in contrast to the Xh-derivative 3'-hydroxy-Xh with catechol substructure, used as positive control. This was shown by the use of sufficient concentration of NBT and other detectors such as hydroxylamine, XTT, cytochrome c and hydroethidine. HPLC analysis of reaction products in a xanthine/XOD/peroxidase system demonstrated beside enhanced inhibition of NBT-formazan by Xh that NBT even prevented oxidation of Xh. p-coumaric acid or ferulic acid could replace Xh in that system, indicating that superoxide detection using NBT is likely jeopardized by interference of phenoxyl-radicals. Furthermore, this study provides evidence that Xh can moderately generate superoxide via auto-oxidation. PMID- 21034358 TI - Reactions of reactive oxygen species (ROS) with curcumin analogues: Structure activity relationship. AB - Three curcumin analogues viz., bisdemethoxy curcumin, monodemethoxy curcumin, and dimethoxycurcumin that differ at the phenolic substitution were synthesized. These compounds have been subjected for free radical reactions with DPPH radicals, superoxide radicals (O(2)(*-)), singlet oxygen ((1)O(2)) and peroxyl radicals (CCl(3)O(2)(*)) and the bimolecular rate constants were determined. The DPPH radical reactions were followed by stopped-flow spectrometer, (1)O(2) reactions by transient luminescence spectrometer, and CCl(3)O(2)(*) reactions using pulse radiolysis technique. The rate constants indicate that the presence of o-methoxy phenolic OH increases its reactivity with DPPH and CCl(3)O(2)(*), while for molecules lacking phenolic OH, this reaction is very sluggish. Reaction of O(2)(*-) and (1)O(2) with curcumin analogues takes place preferably at beta diketone moiety. The studies thus suggested that both phenolic OH and the beta diketone moiety of curcumin are involved in neutralizing the free radicals and their relative scavenging ability depends on the nature of the free radicals. PMID- 21034357 TI - DCPIP (2,6-dichlorophenolindophenol) as a genotype-directed redox chemotherapeutic targeting NQO1*2 breast carcinoma. AB - Accumulative experimental evidence suggests feasibility of chemotherapeutic intervention targeting human cancer cells by pharmacological modulation of cellular oxidative stress. Current efforts aim at personalization of redox chemotherapy through identification of predictive tumour genotypes and redox biomarkers. Based on earlier research demonstrating that anti-melanoma activity of the pro-oxidant 2,6-dichlorophenolindophenol (DCPIP) is antagonized by cellular NAD(P)H:quinone oxidoreductase (NQO1) expression, this study tested DCPIP as a genotype-directed redox chemotherapeutic targeting homozygous NQO1*2 breast carcinoma, a common missense genotype [rs1800566 polymorphism; NP_000894.1:p.Pro187Ser] encoding a functionally impaired NQO1 protein. In a panel of cultured breast carcinoma cell lines and NQO1-transfectants with differential NQO1 expression levels, homozygous NQO1*2 MDA-MB231 cells were hypersensitive to DCPIP-induced caspase-independent cell death that occurred after early onset of oxidative stress with glutathione depletion and loss of genomic integrity. Array analysis revealed upregulated expression of oxidative (GSTM3, HMOX1, EGR1), heat shock (HSPA6, HSPA1A, CRYAB) and genotoxic stress response (GADD45A, CDKN1A) genes confirmed by immunoblot detection of HO-1, Hsp70, Hsp70B', p21 and phospho-p53 (Ser15). In a murine xenograft model of human homozygous NQO1*2-breast carcinoma, systemic administration of DCPIP displayed significant anti-tumour activity, suggesting feasibility of redox chemotherapeutic intervention targeting the NQO1*2 genotype. PMID- 21034359 TI - Role of ascorbate in lung cellular toxicity mediated by light-exposed parenteral nutrition solution. AB - Neonatal lung injury has been induced experimentally by infusion of multivitamin containing light-exposed parenteral nutrition (PN) solutions. The objective was to explore the role of ascorbate in toxic effects of light-exposed PN on primary cultured foetal rat lung epithelial cells. Hydroperoxides were measured in 3% amino acid solutions at baseline, immediately after addition of either multivitamins or ascorbate alone (400 MUg/mL) and again after a 24-h period of exposure to (or protection from) ambient light. Cellular toxicity was assessed by [C(14)]adenine release. Multivitamins or ascorbate alone increased hydroperoxides in PN, which was attenuated by light protection. Light-exposed PN containing multivitamins was more toxic to cells than baseline or light-protected PN. Exposure to ascorbate at concentrations both lower (< 5 MUg/mL) and higher (> 1000 MUg/mL) than normally contained in PN-induced oxidant-mediated cell death, as indicated by protective effects of hydroperoxide and hydroxyl radical scavengers. This study concludes that ascorbate generates toxic amounts of peroxide in PN solutions. The types and physiological importance of hydroperoxides induced by pro-oxidant effects of ascorbate require further evaluation in vivo. PMID- 21034361 TI - Haemoglobin-induced oxidative stress is associated with both endogenous peroxidase activity and H2O2 generation from polyunsaturated fatty acids. AB - Patients with increased haemolytic haemoglobin (Hb) have 10-20-times greater incidence of cardiovascular mortality. The objective of this study was to evaluate the role of Hb peroxidase activity in LDL oxidation. The role of Hb in lipid peroxidation, H(2)O(2) generation and intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) was assessed using NaN(3), a peroxidase inhibitor, catalase, a H(2)O(2) decomposing enzyme and human umbilical vein endothelial cells (HUVECs), respectively. Hb induced H(2)O(2) production by reacting with LDL, linoleate and cell membrane lipid extracts. Hb induced LDL oxidation was inhibited by NaN(3) and catalase. Furthermore, Hb stimulated ICAM-1 and VCAM-1 expression, which was inhibited by the antioxidant, probucol. Thus, the present study suggests that the peroxidase activity of Hb produces atherogenic, oxidized LDL and oxidized polyunsaturated fatty acids (PUFAs) in the cell membrane and reactive oxygen species (ROS) formation mediated Hb-induced ICAM-1 and VCAM-1 expression. PMID- 21034360 TI - Diacylglycerol kinase alpha regulates globular adiponectin-induced reactive oxygen species. AB - It has previously been reported that the globular form of adiponectin (gAd), mature adipocyte-derived cytokine, induced generation of reactive oxygen species (ROS) and nitric oxide (NO) in the murine macrophage cell line RAW 264. This study investigated whether diacylglycerol kinases (DGKs), enzymes functioning in sub-cellular signalling pathways, had a role on gAd-induced ROS generation in RAW 264 cells. Administration of R59022, a specific inhibitor for DGK, reduced gAd induced ROS generation and NO release. RAW 264 cell expressed DGKalpha mRNA. Depression of DGKalpha mRNA by RNA interference significantly reduced the ROS generation in response to gAd treatment. Interestingly, transfection with the DGKalpha-specific small interfering RNA attenuated the expression level of Nox1 mRNA in gAd-treated RAW 264 cells. In addition, the DGKalpha knockdown with siRNA suppressed gAd-induced NO release. PMID- 21034362 TI - Novel cryomilled physically cross-linked biodegradable hydrogel microparticles as carriers for inhalation therapy. AB - In this study, novel biodegradable physically cross-linked hydrogel microparticles were developed and evaluated in-vitro as potential carriers for inhalation therapy. These hydrogel microparticles were prepared to be respirable (desired aerodynamic size) when dry and also designed to avoid the macrophage uptake (attain large swollen size once deposited in lung). The swellable microparticles, prepared using cryomilling, were based on Pluronic(r) F-108 in combination with PEG grafted onto both chitosan (Cs) and its N-phthaloyl derivative (NPHCs). Polymers synthesized in the study were characterized using EA, FTIR, 2D-XRD and DSC. Morphology, particle size, density, biodegradation and moisture content of the microparticles were quantified. Swelling characteristics for both drug-free and drug-loaded microparticles showed excellent size increases (between 700-1300%) and the release profiles indicated sustained release could be achieved for up to 20 days. The respirable microparticles showed drug loading efficiency up to 92%. The enzymatic degradation of developed microparticles started within the first hour and only ~10% weights were remaining after 10 days. In conclusion, these respirable microparticles demonstrated promising in-vitro performance for potential sustained release vectors in pulmonary drug delivery. PMID- 21034364 TI - Encapsulation of ethylhexyl methoxycinnamate, a light-sensitive UV filter, in lipid nanoparticles. AB - The aim of this study was to encapsulate ethylhexyl methoxycinnamate (EMC), a commonly used UVB filter, in a solid lipid matrix in order to obtain microparticles and then nanoparticles to reduce its photo-instability under UV light exposure. Glyceryl behenate, rice bran wax and ozokerite were investigated for encapsulating EMC. The suspensions of nanoparticles contained 70% encapsulated EMC (relative to the lipid mass). The absorbance level at 310 nm of suspensions containing nanoparticles was more than twice that of those containing microparticles. So, decreasing the size of particles improved the efficiency of light protection, regardless of the lipid material used. Moreover, free EMC presented a 30% loss of its efficiency after 2 h of irradiation, whereas the three NLC formulations showed a loss of absorbency between 10% and 21%. The in vitro cutaneous penetration test did not show a higher potential penetration for EMC contained in nanosuspensions compared to free EMC. PMID- 21034363 TI - DNA-chitosan nanoparticles improve DNA vaccine-elicited immunity against Newcastle disease virus through shuttling chicken interleukin-2 gene. AB - In this study, pCAGG-ChIL2 plasmid DNA containing the chicken interleukin-2 (ChIL 2) gene was used to prepare DNA-chitosan nanoparticles (CNPs). The CNPs prepared were spherical, with mean diameters between 100 and 200 nm, have a positive surface charge, and could protect DNA against DNase I degradation. The CNPs prepared were successfully used to transfect the Df-1 cell line with almost no cytotoxicity. CNPs prepared at an amino group to phosphate group ratio (N/P ratio) of 16 provided the highest transfection efficiency (1.1%) in medium with a pH of 6.5. When pCAGG-ChIL2 CNPs were administered to chickens simultaneously with a DNA vaccine against Newcastle disease virus (NDV), haemagglutination inhibition antibody titers and serum interferon-gamma (IFN-gamma) levels were significantly higher than in chickens immunised with the NDV DNA vaccine alone (p < 0.05). The results demonstrate that pCAGG-ChIL2 CNPs improve DNA vaccine elicited immunity against NDV challenge. PMID- 21034365 TI - Solid lipid nanoparticles for transdermal delivery of diclofenac sodium: preparation, characterization and in vitro studies. AB - The aim of this study was to prepare diclofenac sodium (DNa) solid lipid nanoparticles (SLNs) by a modified emulsion/solvent evaporation method for transdermal delivery. Five independent processing parameters including the lipid matrix, emulsifiers, co-emulsifiers, water-dispersed phase and organic phase were assessed systematically to enhance the entrapment of DNa. The SLNs produced by optimal formulation were submicrometre size with low polydispersity index, the entrapment efficiency was about 89% and the drug loading was about 9.5%. Shape and surface morphology were determined by transmission electron microscopy, which revealed the fairly spherical and core-shell shapes of the SLNs. The in vitro release of SLNs showed a two-step release pattern: one initial burst release followed by a second slow-release phase. In the in vitro cutaneous permeation studies, value of flux obtained for DNa solution was higher than that of SLNs suspension. SLNs had also been shown to improve the dermal localization of DNa. PMID- 21034366 TI - Chitosan-associated SLN: in vitro and ex vivo characterization of cyclosporine A loaded ophthalmic systems. AB - The aim of this study was to develop cyclosporine A (CsA) loaded solid lipid nanoparticles (SLN) associated with chitosan (CS), to improve interaction and internalization in corneal cells. The SLN were prepared using high shear homogenization and ultrasound methods with CS in the aqueous phase. The lipid phase was based on Compritol or Precirol. The SLN were characterized for particle size, polydispersity index, morphology, zeta potential and encapsulation efficiency. The systems were freeze-dried to increase physical stability and trehalose was used as a cryo/lyo-protector to stabilize the SLN. The penetration and permeation properties of the SLN were assessed in vitro (cell culture) and ex vivo (excised pig cornea). The cell uptake of SLN was studied by means of confocal laser scanning microscopy. CS-associated SLN based on Compritol were biocompatible and enhanced the permeation/penetration of CsA along with a possible mechanism of internalization/uptake of the nanoparticles both in vitro and ex vivo. PMID- 21034367 TI - Transglutaminase: new insights into gelatin nanoparticle cross-linking. AB - Gelatin nanoparticles (GNPs) have demonstrated to be beneficial as a biodegradable and biocompatible delivery system. So far, nanoparticles prepared by the two-step desolvation technique were subsequently cross-linked by glutaraldehyde to guarantee storage stability. Although in vivo and in vitro toxicological studies have not revealed any glutaraldehyde related undesired effects, an alternative to chemical cross-linking could ease future clinical use in humans. Therefore, the recombinant enzyme microbial transglutaminase was used to examine its cross-linking abilities in nanoparticle production. Various process parameters, such as incubation time, temperature, medium, pH and the particle purification were evaluated regarding their impact on particle size and its distribution. Cross-linking reactions were best at 25 degrees C using an ion free solvent at a neutral pH and have been terminated after 12 h. Preliminary storage stability testing indicated adequate consistency of particle size and particle distribution making transglutaminase a potential candidate for glutaraldehyde substitution in future GNP production. PMID- 21034368 TI - Understanding XDP through imaging, pathology, and genetics. AB - The X-linked dystonia-parkinsonism (XDP) is a severe, progressive, adult-onset, X linked endemic disorder in Filipinos, which is characterized by dystonic movements that start in the third or fourth decade, and replaced by parkinsonism beyond the 10th year of illness. Understanding the pathophysiology of XDP and development of rational therapies will depend on observations from imaging, pathological, and genetic studies. In this paper we summarize the results of these studies on patients with XDP. The cranial magnetic resonance imaging shows hyperintense putaminal rim in both dystonic and parkinsonian stages, and atrophy of the caudate head or putamen in the parkinsonian stage. Neuropathological findings show atrophy of the caudate nucleus and putamen, with mild to severe neuronal loss and gliosis. In the neostriatum, the dystonic phase of XDP shows the involvement of striosomes and matrix sparing, while the later, i.e., parkinsonian phase, shows matrix involvement as well. In the dystonic phase, the loss of striosomal inhibitory projections lead to disinhibition of nigral dopaminergic neurons, perhaps resulting in a hyperkinetic state; while in the parkinsonian phase, severe and critical reduction of matrix-based projection may result in extranigral parkinsonism. Genetic sequencing of the XDP critical region in Xq13.1 has revealed an SVA retrotransposon insertion in an intron of TAF1. This may reduce neuron-specific expression of the TAF1 isoform in the caudate nucleus, and subsequently interfere with the transcription of many neuronal genes, including DRD2. Findings from imaging, pathology, and genetics studies are gradually shedding light on the pathophysiology of XDP, which hopefully will lead to more rational and directed therapies. PMID- 21034369 TI - Pupil light reflex in Parkinson's disease: evaluation with pupillometry. AB - We evaluated pupil light reflex (PLR) in patients with Parkinson's disease (PD) and normal controls by means of pupillometry and explored its possible relation to clinical characteristics in parkinsonian patients. PLR was evaluated using pupillometry in 66 patients with PD without clinical evidence of autonomic dysfunction and 44 healthy matched controls. PLR was elicited by single flash stimuli of 24.6 candelas/m(2) intensity and 20 ms duration, and six parameters were studied after full recording of pupil's movement. A significant increase in latency (T1) and significant decrease in amplitude (R1-R2), maximum constriction velocity (V(max)), as well as maximum acceleration (AC(max)) was found in parkinsonian patients. There was no significant difference in initial radius (R1) and minimum radius (R2) values. Of the parameters studied, AC(max) emerged as a significant predictor for discrimination between PD patients and controls. There was no significant correlation between pupillometry parameters and clinical characteristic of patients (disease duration, stage, and the Unified Parkinson's Disease Rating motor scale). The study demonstrates PLR disorder in PD patients even without overt clinical autonomic dysfunction. Pupillometry appears to be a useful and noninvasive method for exploration of PLR alterations in PD and may prove to be useful for the early detection of subclinical autonomic nervous system dysfunction. PMID- 21034370 TI - Iloperidone: chemistry, pharmacodynamics, pharmacokinetics and metabolism, clinical efficacy, safety and tolerability, regulatory affairs, and an opinion. AB - IMPORTANCE OF THE FIELD: Iloperidone is a newly commercialized second-generation (atypical) antipsychotic approved for the acute treatment of schizophrenia in adults. AREAS COVERED IN THIS REVIEW: the purpose of this review is to describe the pharmacokinetic profile of iloperidone and its clinical implications in the treatment of schizophrenia. Background information is also provided regarding chemistry, pharmacodynamics, clinical efficacy and safety data, and regulatory affairs. WHAT THE READER WILL GAIN: the reader will have an understanding of the pharmacokinetics and overall metabolism of iloperidone within the context of efficacy and safety. TAKE HOME MESSAGE: time to peak plasma concentration occurs in 2 - 4 h but elimination half-life is 18 h for extensive CYP2D6 metabolizers and 33 h for poor CYP2D6 metabolizers, suggesting that once or twice daily dosing would be feasible. Dizziness and/or postural hypotension are the limiting factors for how fast iloperidone can be titrated, and is explained by iloperidone and its metabolites' norepinephrine alpha 1 antagonism. Efficacy of iloperidone appears similar to that for ziprasidone and haloperidol, but iloperidone may be inferior in efficacy to risperidone. Iloperidone can prolong the ECG QT interval. The tolerability profile of iloperidone is noteworthy in terms of modest weight gain, no medically important changes in lipid and glucose, little in the way of prolactin elevation, and an absence of extrapyramidal adverse effects, including akathisia. PMID- 21034371 TI - Antibacterial efficacy of silver nanoparticles of different sizes, surface conditions and synthesis methods. AB - Silver nanoparticles (Ag-nps) are used as a natural biocide to prevent undesired bacterial growth in clothing and cosmetics. The objective of this study was to assess the antibacterial efficacy of Ag-nps of different sizes, surface conditions, and synthesis methods against Escherichia coli, Ag-resistant E. coli, Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), and Salmonella sp. Ag-nps samples were synthesized by: Base reduction with unmodified surfaces and used as synthesized ('unwashed'; 20, 50 and 80 nm) or after 20 phosphate buffer washes ('washed'; 20, 50 and 80 nm), or synthesized by laser ablation with carbon stabilized surfaces ('carbon-coated'; 25 and 35 nm). Unwashed Ag-nps were toxic to all bacterial strains at concentrations between 3.0-8.0 MUg/ml. The washed Ag nps and carbon-coated Ag-nps were toxic to all bacterial strains except Ag resistant E. coli at concentrations between 64.0-1024.0 MUg/ml. Ag-resistant E. coli died only when treated with unwashed Ag-nps or its supernatant, both of which contained formaldehyde. PMID- 21034372 TI - Particles which may occur in food or food packaging can exert cytotoxicity and (oxidative) DNA damage in target cells of the human intestine. PMID- 21034373 TI - Immune responses of BALB/c mice to subcutaneously injected multi-walled carbon nanotubes. AB - Carbon nanotubes have been shown to have the ability to transport therapeutic and detective reagents into cells. However, the rapid advances in new carbon nanotube based materials and technologies have raised concerns about their safety. Such concerns require a fundamental understanding of the toxicological properties of carbon nanotubes. In particular, the use of carbon nanotubes as drug or probe delivery platforms may depend on the prevention of stimulatory side-effects to the immune system. In this study, we investigated the immunological properties of oxidized water dispersible multi-walled carbon nanotubes (MWCNTs) in healthy BALB/c mice. We injected the MWCNTs subcutaneously, and the immune responses of the mice were monitored over time. We show that the MWCNTs induce complement activation and the production of pro-inflammatory cytokines early after injection of the mice, and that the levels of complement and cytokines return to normal levels over time. With the exception of the lymph nodes, there was no obvious accumulation of MWCNTs observed in the liver, spleen, kidney, or heart. In addition, we did not observe injury in the organs or lymph nodes. Our results indicate that local, subcutaneous administration of MWCNTs induces obvious short term immunological reactions, which can be eliminated over time. PMID- 21034374 TI - Perceptions and prescribing considerations among US psychiatrists regarding drug drug interactions associated with oral atypical antipsychotics. AB - OBJECTIVE: Contemporary literature has demonstrated the potential for drug-drug interactions (DDIs) with oral atypical antipsychotic (OAA) agents. However, less is known about psychiatrists' perceptions about DDIs when prescribing OAAs. This study addresses this gap by surveying US psychiatrists about their perceptions of DDI when prescribing a new OAA. METHODS: An online survey of 131 US psychiatrists was conducted to assess if considerations of DDIs were taken into account when prescribing a new OAA within their practice and prescribing patterns. For each survey question, results are presented as the proportion of psychiatrists in each rating category. Data were collected on physicians' awareness and concern about DDIs when prescribing OAAs, perception of frequency and severity of OAA-related DDIs, and methods of monitoring and preventing OAA-related DDIs. RESULTS: Of the psychiatrists surveyed, 9.2% considered themselves well-informed (rating of 10/10) about OAA-related DDIs. In the 3-month period preceding the survey date, psychiatrists reported that on average 7.5 (SD 12.4) of their patients experienced a potentially OAA-related DDI event which represented an average of 2.5% (SD 4.8%) of their total number of patients. In all, 19.8% of the psychiatrists reported they were currently tracking the level of confirmed OAA related DDI events in their practices; these psychiatrists reported a mean 21.1% incidence rate of confirmed DDI events experienced by patients starting a new OAA therapy in their practice. The psychiatrists ranked the risks of cardiovascular events and of neurological impairment as the two most frequent and severe potential DDI events to consider when prescribing a new OAA, in combination with selective serotonin reuptake inhibitors, mood stabilizers, and antihypertensive agents, the drugs most frequently associated with the most severe OAA-related DDIs. CONCLUSIONS: Psychiatrists, on recall of recent cases, perceive DDI events to be frequent in patients starting a new OAA therapy. While there appears to be some awareness of DDI-related issues among psychiatrists, this survey of psychiatrists perceptions suggests the need for systematic tracking of OAA related DDI events and additional psychiatrist training on optimal OAA choice to prevent DDIs. PMID- 21034376 TI - Low doses of transdermal fentanyl in opioid-naive patients with cancer pain. AB - OBJECTIVE: The aim of this study was to evaluate the effect and tolerability of low doses of transdermal (TD) fentanyl patches in opioid-naive patients with cancer pain. METHODS: This was a nonrandomized, open-label, uncontrolled study in fifty consecutive opioid-naive patients with advanced cancer and moderate pain. TD fentanyl was initiated at a dose of 12 ug/h. Doses were then adjusted according to the clinical response. Pain intensity, opioid-related adverse effects, TD fentanyl doses, and quality of life were monitored over 4 weeks. The time to dose stabilization and indexes of dose escalation were also calculated. RESULTS: Thirty-one patients completed all 4 weeks of the study. Pain control was achieved within a mean of 1.7 days after the start of TS fentanyl therapy. Significant differences in TD fentanyl doses were observed during the study period (P = 0.03). Mean doses were doubled 4 weeks after starting the treatment. The level of adverse effects was acceptable in most patients and only a minority of patients discontinued the treatment (13.8%). CONCLUSION: Low doses of TD fentanyl were well tolerated and effective. Observations from this study suggest that randomized, controlled, double-blind studies of TD fentanyl 12 ug/h in opioid-naive patients with cancer pain may be warranted. PMID- 21034375 TI - Comparison of escitalopram vs. citalopram and venlafaxine in the treatment of major depression in Spain: clinical and economic consequences. AB - STUDY OBJECTIVE: Population based study to determine the clinical consequences and economic impact of using escitalopram (ESC) vs. citalopram (CIT) and venlafaxine (VEN) in patients who initiate treatment for a new episode of major depression (MD) in real life conditions of outpatient practice. METHODS: Observational, multicenter, retrospective study conducted using computerized medical records (administrative databases) of patients treated in six primary care centers and two hospitals between January 2003 and March 2007. STUDY POPULATION: patients >20 years of age diagnosed with a new episode of MD who initiate treatment with ESC, CIT or VEN who had not received any antidepressant treatment within the previous 6 months, and were followed for 18 months or more. MAIN VARIABLES: socio-demographic variables, remission (defined as a patient completing 6 months of therapy), comorbidity, annual health care costs (medical visits, diagnostic and therapeutic tests, hospitalizations, emergency room and psychoactive drugs prescribed) and non-health care costs (productivity losses at work, mainly sick leave and disability). STATISTICAL ANALYSES: logistic regression and ANCOVA models. RESULTS: A total of 965 patients (ESC = 131; CIT = 491; VEN = 343) were identified and met study criteria. ESC-treated patients were younger, with a higher proportion of males, and had a lower specific comorbidity (p < 0.01). ESC-treated patients achieved higher remission rates compared to CIT (58.0% vs. 38.3%) or VEN patients (32.4%), p < 0.001, and had lower productivity work losses compared to VEN patients (32.7 vs. 43.8 days), p = 0.042. No differences in productivity work losses were observed between ESC and CIT patients. Compared to the ESC group, higher costs in average/unit of psychoactive drugs were found in the VEN group (?643.00), p = 0.003, whereas no differences were observed between the ESC and CIT groups (?294.70 vs. ?265.20). In the corrected model, total costs (health care and non-health care cost) were lower with ESC (?2276.20) compared to CIT (?3093.80), p = 0.047 and VEN (?3801.20), p = 0.045. CONCLUSIONS: ESC appears to be dominant in the treatment of new MD episodes when compared to CIT and VEN, resulting in higher remission rates and lower total costs. PMID- 21034377 TI - A comparison of preferences for two GLP-1 products--liraglutide and exenatide- for the treatment of type 2 diabetes. AB - OBJECTIVE: To use time trade-off (TTO) to compare patient preferences for profiles of two glucagon-like peptide (GLP-1) products for the treatment of type 2 diabetes (liraglutide and exenatide) that vary on four key attributes - efficacy (as measured by hemoglobin A(1C)), incidence of nausea, incidence of hypoglycemia, and dosing frequency (QD vs. BID) - and measure the contribution of those attributes to preferences. METHODS: A total of 382 people with T2DM were recruited to participate in an internet-based survey consisting of a series of health-related questions, a conjoint exercise and a set of time trade-off items. In the conjoint exercise, respondents were presented with eight pairs of hypothetical GLP-1 profiles, and completed a time-tradeoff exercise for each pair. RESULTS: The product profile representing liraglutide was preferred by 96% of respondents and resulted in significantly higher health utilities (0.038) than the product profile representing exenatide (0.978 vs. 0.94, p < 0.05). Estimated preference scores from the conjoint analysis revealed that efficacy measured by hemoglobin A(1C) is the most important attribute, followed by nausea, hypoglycemia, and dosing schedule. LIMITATIONS: On-line participants may not represent 'typical' type 2 diabetes patients, and brief product profiles represented results from clinical trials, not clinical practice CONCLUSION: Based on the four attributes presented, patients prefer liraglutide over exenatide. Preference is based on superior efficacy and less nausea more than less hypoglycemia and once-daily dosing. PMID- 21034378 TI - The impact of pain on labor force participation, absenteeism and presenteeism in the European Union. AB - OBJECTIVES: The aims of this paper are to generate estimates of the association between the experience and burden of pain, by severity and frequency, with (1) labor force participation and workforce status in five EU countries (the UK, France, Spain, Germany and Italy) and (2) patterns of absenteeism and presenteeism for the employed workforce. METHODS: Data are from the internet based 2008 National Health and Wellness Survey (NHWS). This survey covers both those who report experiencing pain in the last month as well as the no pain population. A series of regression models are developed with the no pain group as the reference category. The impact of pain, categorized by severity and frequency reported, is assessed within a labor supply framework for (1) labor force participation and (2) absenteeism and presenteeism. In the former case both binomial and multinomial logistic models are estimated; in the latter case ordered logit models are estimated. RESULTS: The results demonstrate that, in the context of health status, the experience of frequent severe and moderate pain has a dominant, independent and negative association with labor force participation and employment status as well as absenteeism and presenteeism. The presence of severe daily pain is associated with a 20-point reduction in the probability of being employed full-time; with moderate daily pain associated with a 10-point reduction. The impact of pain is far greater than the potential impact of other health status measures (e.g., chronic comorbidities and BMI). The experience of pain, notably severe and frequent pain, also outstrips the impact of other health status factors in absenteeism and presenteeism. CONCLUSIONS: The experience of pain, in particular severe daily pain, has a substantial negative association with labor force participation in these five European countries as well as reported absenteeism and presenteeism. As a measure of health status, it clearly outweighs other health status measures. Whether or not pain is considered as a disease in its own right, the experience of chronic pain, as defined here, presents policy makers with a major challenge. Programs to relieve the burden of pain in the community clearly have the potential for substantial benefits from societal, individual and employer perspectives. PMID- 21034379 TI - Febrile convulsions after 2010 seasonal trivalent influenza vaccine: implications for vaccine safety surveillance in Australia. PMID- 21034380 TI - "Time is muscle" in reperfusing occluded coronary arteries in acute myocardial infarction. PMID- 21034381 TI - Reperfusion therapy in the acute management of ST-segment-elevation myocardial infarction in Australia: findings from the ACACIA registry. AB - OBJECTIVE: To describe the contemporary management and outcomes of patients presenting with ST-segment-elevation myocardial infarction (STEMI) in Australia. DESIGN, PARTICIPANTS AND SETTING: Observational analysis of data for patients who presented with suspected STEMI and enrolled in the Australian Acute Coronary Syndrome Prospective Audit from 1 November 2005 to 31 July 2007. MAIN OUTCOME MEASURES: Factors associated with use of reperfusion therapy and timely use of reperfusion therapy, and the effects of reperfusion on mortality. RESULTS: In total, 755 patients had suspected STEMI. Median time to presentation was 105 minutes (IQR, 60-235 minutes). Reperfusion therapy was used in 66.9% of patients (505/755), and timely reperfusion therapy in 23.1% (174/755). Thombolysis was administered in 39.2% of those who received reperfusion therapy (198/505), while 60.8% (307/505) received primary percutaneous intervention. Cardiac arrest (OR, 2.83; P = 0.001) and treatment under the auspices of a cardiology unit (OR, 2.14; P = 0.02) were associated with use of reperfusion therapy. A normal electrocardiogram on presentation (OR, 0.42; P = 0.01), left bundle branch block (OR, 0.18; P = 0.001), acute pulmonary oedema (OR, 0.34; P < 0.01), history of diabetes (OR, 0.54; P < 0.01), and previous lesion on angiogram of > 50% (OR, 0.51; P = 0.001) were associated with not using reperfusion. In hospital mortality was 4.0% (30/755), mortality at 30 days was 4.8% (36/755), and mortality at 1 year was 7.8% (59/755). Receiving reperfusion therapy of any kind was associated with decreased 12-month mortality (hazard ratio [HR], 0.44; 95% CI, 0.25-0.78; P < 0.01). Timely reperfusion was associated with a reduction in mortality of 78% (HR, 0.22; P = 0.04). There were no significant differences in early and late mortality in rural patients compared with metropolitan patients (P = 0.66). CONCLUSION: Timely reperfusion, not the modality of reperfusion, was associated with significant outcome benefits. Australian use of timely or any reperfusion remains poor and incomplete. PMID- 21034382 TI - Increased iodine deficiency in Victoria, Australia: analysis of neonatal thyroid stimulating hormone data, 2001 to 2006. AB - OBJECTIVE: To use neonatal thyroid-stimulating hormone (TSH) concentration data to measure the iodine status of the population of the Australian state of Victoria. DESIGN, PARTICIPANTS AND SETTING: Retrospective analysis of the results of 368,552 neonatal heel-prick blood tests for TSH concentration in Victoria in the years 2001-2006. MAIN OUTCOME MEASURES: Iodine deficiency as indicated by a mean percentage of neonatal TSH concentrations > 5 mIU/L of over 3% in accordance with World Health Organization, United Nations Children's Fund and International Council for the Control of Iodine Deficiency Disorder criteria; comparison of findings for the nine Department of Human Services health regions in Victoria. RESULTS: The mean percentage of neonatal TSH concentrations > 5 mIU/L ranged from 4.07% in 2001 to 9.65% in 2006, and this increase was statistically significant (P < 0.001). The populations of all nine Victorian health regions showed increasing iodine deficiency over the study period. Metropolitan populations had higher iodine deficiency than non-metropolitan populations, and this difference was also statistically significant (P < 0.05). These results are consistent with urinary iodine excretion research in Victoria. CONCLUSIONS: The high percentage of elevated TSH concentrations among newborns is of concern and requires ongoing monitoring. Neonatal TSH assay is part of routine screening in Australia, and thus offers an effective and economical method of monitoring population iodine status. PMID- 21034383 TI - Self-injury in Australia: a community survey. AB - OBJECTIVE: To understand self-injury and its correlates in the Australian population. DESIGN, PARTICIPANTS AND SETTING: Cross-sectional survey, using computer-assisted telephone interview, of a representative sample of 12,006 Australians from randomly selected households. MAIN OUTCOME MEASURES: Data on demographics, self-injury, psychiatric morbidity, substance use, suicidality, disclosure and help-seeking. RESULTS: In the 4 weeks before the survey, 1.1% of the sample self-injured. For females, self-injury peaked in 15-24-year-olds; for males, it peaked in 10-19-year-olds. The youngest self-injurers were nine boys and three girls in the 10-14-year age group, and the oldest were one female and one male in the 75-84-year age group. Mean age of onset was 17 years, but the oldest age of onset was 44 years for males and 60 years for females. No statistically significant differences existed between those who did and did not self-injure on sex, socioeconomic status or Indigenous status. Most common self injury method was cutting; most common motivation was to manage emotions. Frequency of self-injury during the 4-week period ranged from 1 to 50 instances (mean, 7). Self-injurers were significantly more psychologically distressed, and also more likely to use substances. Adults who self-injured were more likely to have received a psychiatric diagnosis. Self-injurers were more likely to have experienced recent suicidal ideation (OR, 11.56; 95% CI, 8.14-16.41), and have ever attempted suicide (OR, 8.51; 95% CI, 5.70-12.69). Most respondents told someone about their self-injury but fewer than half sought help. CONCLUSION: The prevalence of self-injury in Australia in the 4 weeks before the survey was substantial and self-injury may begin at older ages than previously reported. Self-injurers are more likely to have mental health problems and are at higher risk of suicidal thoughts and behaviour than non-self-injurers, and many self injurers do not seek help. PMID- 21034384 TI - A case-crossover analysis of traffic-related air pollution and emergency department presentations for asthma in Perth, Western Australia. AB - OBJECTIVE: To determine whether changes in 24-hour average background ozone (O3), nitrogen dioxide (NO2), carbon monoxide (CO) and particulates < 10 MUm (PM10) increase the risk of hospital emergency department (ED) presentations for asthma among children. DESIGN, SETTING AND SUBJECTS: A time-stratified case-crossover method was used to analyse data of 603 children and young adults aged 0-19 years who were resident in a south-west metropolitan area of Perth, Western Australia, and who had presented with asthma at any public ED within Perth between 1 January 2002 and 31 December 2006. Effect sizes were assessed in relation to age group, sex and season of exposure. City-wide background air pollution was estimated from air monitoring network data. MAIN OUTCOME MEASURES: ED presentation with asthma. RESULTS: Patients 0-4 years with 1-day lagged exposure to NO2 and CO showed the most significant risk of ED presentation for asthma. An interquartile range (IQR) increase in NO2 resulted in an odds ratio (OR) of 1.70 (95% CI, 1.08-2.69). An IQR increase in CO resulted in an OR of 1.40 (95% CI, 1.06-1.84). CONCLUSIONS: The effect sizes observed in this study were higher than those of past studies, and indicated that children aged 0-4 years were the most vulnerable to the effects of air pollution. The period of exposure most clinically relevant is the day before ED presentation. PMID- 21034385 TI - Haemodialysis outcomes of Aboriginal and Torres Strait Islander patients of remote Kimberley region origin. AB - OBJECTIVES: To compare the clinical outcomes and mortality rates of Aboriginal and Torres Strait Islander people of Kimberley origin receiving haemodialysis (HD) treatment with other subsets of Aboriginal and Torres Strait Islander HD patients (Northern Territory, Western Australia excluding the Kimberley region, the rest of Australia) and Australian non-Indigenous HD patients. DESIGN, PARTICIPANTS AND SETTING: Retrospective identification of Aboriginal and Torres Strait Islander patients of Kimberley origin and analysis of secondary data from the Australia and New Zealand Dialysis and Transplant Registry; this group was compared with other Australian patients receiving HD treatment from 1 January 2003 to 31 December 2007. MAIN OUTCOME MEASURES: Clinical outcome measures; comorbid conditions; death rates per 100 patient-years, unadjusted and adjusted (for age, sex, comorbid conditions, late referral to nephrologist treatment). RESULTS: Seventy per cent of HD treatments for Aboriginal and Torres Strait Islander patients of Kimberley origin was provided in the Kimberley. They had comparable adjusted mortality rates to non-Indigenous Australian patients (adjusted mortality rate ratio, 0.80; 95% CI, 0.51-1.23). CONCLUSIONS: This is the first report showing similar mortality rates for Aboriginal and Torres Strait Islander people exclusively from a remote area of Australia and non-Indigenous Australians receiving HD treatment. HD treatment delivered closer to home can be safe and effective in remote areas. PMID- 21034387 TI - Diagnosis and management of iron deficiency anaemia: a clinical update. AB - Iron deficiency anaemia (IDA) remains prevalent in Australia and worldwide, especially among high-risk groups. IDA may be effectively diagnosed in most cases by full blood examination and serum ferritin level. Serum iron levels should not be used to diagnose iron deficiency. Although iron deficiency may be due to physiological demands in growing children, adolescents and pregnant women, the underlying cause(s) should be sought. Patients without a clear physiological explanation for iron deficiency (especially men and postmenopausal women) should be evaluated by gastroscopy/colonoscopy to exclude a source of gastrointestinal bleeding, particularly a malignant lesion. Patients with IDA should be assessed for coeliac disease. Oral iron therapy, in appropriate doses and for a sufficient duration, is an effective first-line strategy for most patients. In selected patients for whom intravenous (IV) iron therapy is indicated, current formulations can be safely administered in outpatient treatment centres and are relatively inexpensive. Red cell transfusion is inappropriate therapy for IDA unless an immediate increase in oxygen delivery is required, such as when the patient is experiencing end-organ compromise (eg, angina pectoris or cardiac failure), or IDA is complicated by serious, acute ongoing bleeding. Consensus methods for administration of available IV iron products are needed to improve the utilisation of these formulations in Australia and reduce inappropriate transfusion. New-generation IV products, supported by high-quality evidence of safety and efficacy, may facilitate rapid administration of higher doses of iron, and may make it easier to integrate IV iron replacement into routine care. PMID- 21034386 TI - The health of urban Aboriginal people: insufficient data to close the gap. AB - The Australian Government has committed to reducing Indigenous disadvantage, including closing the life-expectancy gap within a generation, and to halving the gap in mortality rates for children under 5 years of age within a decade. Sixty per cent of the health gap between Indigenous and non-Indigenous Australians is attributable to the health of Indigenous people living in non-remote areas of Australia. We conducted a brief review of recent Australian original research publications on the health of the 53% of Indigenous people who live in urban areas, and found that data are sparse; there were only 63 studies in the past 5 years (11% of all articles about Indigenous health during this period). Although Indigenous Australians living in remote areas experience greater health disparity, the government will not achieve its aims without paying due attention to the non-remote-living population. More research is required, and particularly research that actually tests the impact of policies and programs. PMID- 21034388 TI - The unsettled baby: crying out for an integrated, multidisciplinary primary care approach. AB - Unsettled behaviour in the first few months of life is a common clinical problem, with the associated risks of postnatal depression, premature cessation of breastfeeding, long-term psychological disturbance, and child abuse. Parents of new babies complain of difficulty accessing appropriate care and receiving conflicting advice. Although organic disturbance is implicated in only 5% of cases, gastro-oesophageal reflux disease, food allergies and lactose intolerance are often mistakenly diagnosed in unsettled babies. There is no evidence that acid-suppressive medications help in treating unsettled behaviour and, until the hypothesis that proton-pump inhibitors may predispose to food allergies has been properly investigated, treatment with acid-suppressive medications should be avoided in this population. Although unsettled behaviour in infants is commonly a transient neurodevelopmental phenomenon that peaks at 6 weeks of age, failure to diagnose other correctable problems, including breastfeeding difficulty and cows milk allergy, risks entrenching anxiety and disrupted mother-infant interactions in the long term. In the current climate of health system reform, the design and evaluation of an integrated, evidence-based, multidisciplinary primary care approach to management of unsettled babies and their mothers is a priority. PMID- 21034389 TI - Privacy and the use of health data for research. AB - OBJECTIVE: We reviewed resources for researchers interested in privacy issues surrounding secondary use of health data for research. These included applicable privacy regulations and available information on privacy perception in Australia. The review is timely because the current Australian Population Health Research Network infrastructure investments are likely to attract new researchers to the field. DATA SOURCES: We used Australian federal, state and territory regulations and programs, polls and surveys, public speeches and academic literature, and some international resources. DATA SYNTHESIS: We identify four themes (de identification, consent, bias and participation) emerging as areas of concern from the review, and discuss issues relevant to these themes. We provide arguments that excessive privacy regulation has a negative effect on public health research. CONCLUSIONS: There is little evidence of privacy complaints or breaches in health research, but significant concerns about consent and de identification appear to persist in the community. New researchers need to take account of privacy regulation and may wish to take account of privacy perception when designing study and consent processes. PMID- 21034390 TI - Community-acquired Klebsiella pneumoniae liver abscesses - an "emerging disease" in Australia. AB - Liver abscess due to Klebsiella pneumoniae infection has been widely reported in Asia, but rarely reported in Australia until now. We describe four previously well Asian-born patients who presented across Australia with community-acquired K. pneumoniae liver abscesses. With prompt recognition, appropriate antibiotics and early drainage, outcome is significantly improved, although vigilance for metastatic complications is essential. PMID- 21034391 TI - The importance of early diagnosis of herpes zoster myelitis. PMID- 21034392 TI - Acute coronary syndromes: consensus recommendations for translating knowledge into action. PMID- 21034393 TI - Scurvy and stroke - is there an association? PMID- 21034394 TI - Nebulised frusemide for the symptomatic treatment of end-stage congestive heart failure. PMID- 21034395 TI - Improving access for anti-tumour necrosis factor-a therapy in inflammatory bowel disease. PMID- 21034396 TI - Guidelines for youth depression: time to incorporate new perspectives. PMID- 21034397 TI - Measurement of jugular venous pressure. PMID- 21034398 TI - Lost opportunities with Australia's health workforce? PMID- 21034399 TI - Home haemodialysis in Australia - is the wheel turning full circle? PMID- 21034400 TI - How can we reduce alcohol-related road crash deaths among young Australians? PMID- 21034401 TI - Recent progress of small molecular VEGFR inhibitors as anticancer agents. AB - Vascular endothelial growth factor receptor (VEGFR) is an important receptor tyrosine kinase (RTK) in the induction of angiogenesis. Abnormal activation of VEGFR leads to several disorders including cancer. Nowadays, inhibition of VEGFR kinase has been one of the most powerful clinical strategies in cancer treatment and great efforts to design and synthesize small molecular VEGFR inhibitors for cancer research have been made in recent years. This review highlights the major progress and development of them, including their structure and pharmacophore features, biological activities and structure-activity relationships (SAR). Special attentions are paid to the compounds available in market or in advanced clinical stages. PMID- 21034402 TI - Cardiovascular effects of glucagon-like peptide 1. AB - Glucagon-like peptide-1 (GLP-1) is involved in satiety control and glucose homeostasis. Besides, GLP-1 has cardiovascular effects. In experimental models, GLP-1 increases cardiac output and exerts a direct vasodilatory effect. In animals with dilated cardiomyopathy GLP-1 improves left ventricular performance. Human data demonstrated that GLP-1 reduces arterial blood pressure, improves endothelial function in individuals with diabetes and left ventricular function in patients with heart failure. Administration of GLP-1 increases ejection fraction in acute myocardial infraction and reduces ischemia-reperfusion myocardial injury. Although more research is needed, these data suggest that GLP 1 may be used with promising results in patients with heart failure, acute myocardial infarction and revascularization procedures in addition to the standard therapy. PMID- 21034403 TI - Recent advances and future perspectives of triazole analogs as promising antiviral agents. AB - Emergence of severe viral infections in recent years and limited availability of antiviral chemotherapeutic agents for prevention and treatment of these infections are among the most common causes of human illness and death. Therefore, there is an urgent need to develop antiviral drugs that have a potentially critical role in the prevention and treatment of various fatal and debilitating viral infections. Triazole derivatives occupy a pivotal position in modern medicinal chemistry and several have found applications as medicines. A large volume of research has been carried out on triazole and their derivatives for antiviral activity and pharmacological importance of this scaffold has been well established. This review is primarily addressed to description of the recent advances in the synthesis and evaluation of triazole derivatives as antiviral agents which may facilitate the development of more potent and effective antiviral agents. PMID- 21034404 TI - Kavalactone pharmacophores for major cellular drug targets. AB - A number of studies have identified differential kavalactone activity against a variety of molecular targets, including P-glycoprotein (Pgp), platelet monoamine oxidase (MAO-B), transcription factor binding domains, pregnane X (PXR) and GABA receptors, and cytochrome P450 and cyclo-oxygenase (COX) enzymes. The molecular structure of the kavalactones possesses a pharmacophore for several of these targets. In most cases, conformational stability is more significant than the substituents present. The analysis of these pharmacophores provides important insights for future medicinal chemistry-based approaches to kavalactone-type drugs. PMID- 21034405 TI - Anti-cancer effect of spinach glycoglycerolipids as angiogenesis inhibitors based on the selective inhibition of DNA polymerase activity. AB - Plants contain major glycoglycerolipids, such as monogalactosyl diacylglycerol (MGDG), digalactosyl diacylglycerol (DGDG) and sulfoquinovosyl diacylglycerol (SQDG), in the chloroplast membrane. The bioactivities of purified MGDG, DGDG and SQDG from spinach have been investigated extensively. MGDG and SQDG have been shown to inhibit the activities of mammalian DNA polymerases, but DGDG has no such inhibitory effect. The effect of these glycoglycerolipids on cancer cells, angiogenesis and solid tumor growth might be mediated via their inhibition of replicative DNA polymerase activities. On the basis of these findings, we discuss the mode of action of plant chloroplast glycoglycerolipids as anti-cancer therapeutic agents. PMID- 21034406 TI - Small molecule inhibitors of NF-kB and JAK/STAT signal transduction pathways as promising anti-inflammatory therapeutics. AB - In the current review, we discuss the role of NF-kB and JAK/STAT signaling pathways and their small molecule regulators in the therapy of inflammatory diseases. Considering potential harmful effects directly assigned to the COX-2 inhibition, novel therapeutically-relevant biological targets such as NF-kB and JAK/STAT signaling pathways have received a growing attention. Here we summarize recent progress in the identification and development of novel, clinically approved or evaluated small molecule regulators of these signaling cascades as promising anti-inflammatory therapeutics. In addition, we illustrate key structural modifications and bioisosteric transformations among these inhibitors to provide a helpful basis for further development of novel small molecule anti inflammatory agents. PMID- 21034407 TI - Carbohydrate-based bioactive compounds for medicinal chemistry applications. AB - In this article we review our work over the years on carbohydrates and carbohydrate mimetics and their applications in medicinal chemistry. In the first part of the review innovative synthetic methods, such as the chemoselective glycosylation method originally developed by our group and its applications to the synthesis of neoglycoconjugates (neoglycopeptides, oligosaccharide mimetics, neoglycolipids, etc...) will be presented. The high density of functional groups (hydroxyls) on the monosaccharides and the structural role of sugars forming the core of complex glycans in scaffolding and orienting the external sugar units for the interaction with receptors, inspired us and others to use sugars as scaffolds for the construction of pharmacologically active compounds. In the second part of this review, we will present some examples of bioactive and pharmacologically active compounds obtained by decorating monosaccharide scaffolds with pharmacophore groups. Sugar-derived protein ligands were also used as chemical probes to study the interaction of their target with other proteins in the cell. In this context, sugar mimetics and sugar-derived compounds have been employed as tools for exploring biology according to the "chemical genetic" approach. PMID- 21034408 TI - Targeting the nucleus: an overview of Auger-electron radionuclide therapy. AB - The review presented here lays out the present state of the art in the field of radionuclide therapies specifically targeted against the nucleus of cancer cells, focussing on the use of Auger-electron-emitters. Nuclear localisation of radionuclides increases DNA damage and cell kill, and, in the case of Auger electron therapy, is deemed necessary for therapeutic effect. Several strategies will be discussed to direct radionuclides to the nucleoplasm, even to specific protein targets within the nucleus. An overview is given of the applications of Auger-electron-emitting radionuclide therapy targeting the nucleus. Finally, a few suggestions are made as how radioimmunotherapy with nuclear targets can be improved, and the challenges that might be met, such as how to perform accurate dosimetry measurements, are examined. PMID- 21034409 TI - Current concepts and future directions in radioimmunotherapy. AB - Radioimmunotherapy relies on the principles of immunotherapy, but expands the cytotoxic effects of the antibody by complexing it with a radiation-emitting particle. If we consider radioimmunotherapy as a step beyond immunotherapy of cancer, the step was prompted by the (relative) failure of the latter. The conventional way to explain the failure is a lack of intrinsic killing effect and a lack of penetration into poorly vascularized tumor masses. The addition of a radioactive label (usually a beta-emitter) to the antibody would improve both. Radiation is lethal and the type of radiation used (beta rays) has a sufficient range to overcome the lack of antibody penetration. At present, the most successful (and FDA approved) radioimmunotherapy agents for lymphomas are anti CD20 monoclonal antibodies. Rituximab (Rituxan((r))) is a chimeric antibody, used as a non-radioactive antibody and to pre-load the patient when Zevalin((r)) is used. Zevalin((r)) is the Yttrium-90 ((90)Y) or Indium-111 ((111)In) labeled form of Ibritumomab Tiuxetan. Bexxar((r)) is the Iodine-131 ((131)I) labeled form of Tositumomab. Ibritumomab Tiuxetan and Tositumomab are murine anti-CD20 monoclonal antibodies, not chimeric antibodies. Promising research is being done to utilize radioimmunotherapy earlier in the treatment algorithm for lymphoma, including as initial, consolidation, and salvage therapies. However, despite more than 8 years since initial regulatory approval, radioimmunotherapy still has not achieved widespread use due to a combination of medical, scientific, logistic, and financial barriers. Other experimental uses for radioimmunotherapy include other solid tumors to treat infections. Optimization can potentially be done with pre targeting and bi-specific antibodies. Alpha particle and Auger electron emitters show promise as future radioimmunotherapy agents but are mostly still in pre clinical stages. PMID- 21034410 TI - Radioembolization of hepatocellular carcinoma. AB - In this review paper, available data on radioembolization of unresectable hepatocellular carcinoma (HCC) using commercially available radiopharmaceuticals, respectively (131)I-Lipiodol, Therasphere (glass-microspheres) and SIRspheres (resin-microspheres) are reviewed. In the palliative setting, (131)I-Lipiodol was shown to yield response rates of 17-92% which in patients with portal vein thrombosis (PVT) translate into a survival benefit as evidenced by a phase III randomized trial. Furthermore, in terms of efficacy, (131)I-Lipiodol is as efficacious as trans-arterial chemoembolization (TACE) but far better tolerated. In the adjuvant setting, improved recurrence-free and overall survival when compared to surgery alone have been reported but these results warrant confirmation by randomized prospective trials. Similar to (131)I-Lipiodol, when administered in a palliative setting, radioembolization using (90)Y microspheres was proven effective for selected cases of non-resectable HCC and well tolerated. Available data suggest that Therasphere treatment outperforms TACE both in terms of response as in terms of event-free survival in unresectable HCC. However, this finding needs confirmation by randomized prospective trials. Therasphere treatment was also shown to limit progression of HCC allowing potential candidates for orthotopic liver transplantation (OLT) more time to wait for donor organs as well as to downstage the HCC disease to such an extent that patients that were initially not, as yet become eligible for OLT with a gain in survival. Finally, Therasphere was shown to be safe and efficacious in HCC patients presenting with PVT, reason for which approval was granted for this indication by the FDA. PMID- 21034411 TI - Targeted radiotherapy of bone malignancies. AB - The severe pain associated with many disorders affecting bone account for a large proportion of cases of patient morbidity, due to the encumbrance of mobility and therefore, compromised quality of life. Skeletal metastasis is one such condition, which generally complicates the treatment of the primary cancers such as that of the breast, prostate and lung - causing intense pain and eventually even mortality. This paper presents examples of various approaches explored and proposed in the ongoing search to identify better radiopharmaceuticals for the treatment of bone disorders such as metastases. The primary objective of these developments is to alleviate the debilitating pain commonly associated with bone lesions. The efficacy of a radiotherapeutic agent intended for the treatment of diseased bone is particularly dependent on the radiation dose to the tumor cells and on the extent to which suppression of bone marrow or other critical organs can be avoided. Therefore, the design rationale requires careful consideration of the choice radionuclide and especially ensuring that the drug selectively targets the lesion or tumor site. The options pursued include the use of radioisotopes with an intrinsic affinity for bone, such as (89)Sr or (223)Ra, or the design of bone-seeking ligands, such as phosphonates, to selectively deliver the radionuclide to the target, e.g. [(153)Sm]Sm-EDTMP. A combination of the above may too be possible, where the bone seeking ligand facilitates the selective accumulation of a radionuclide, which by itself is also bone homing. In terms of therapeutic application radionuclides with various decay modes are proposed, including beta (-) emitters: (153)Sm, (89)Sr, (186)Re, (188)Re, (32)P, (177)Lu and (170)Tm; alpha (alpha) emitters: (223)Ra and (225)Ra; and Auger or conversion electron emitter: (117)mSn. From a purely diagnostic perspective, the radioisotopes used for imaging include the well known photon emitting (99)mTc, and positron emitters (18)F and (68)Ga. The current status in the development and application of internal radiotherapy for the palliative treatment of bone pain will be discussed, summarizing the progress made and challenges encountered in the process to realizing an effective drug candidate. PMID- 21034412 TI - Targeted molecular radiotherapy. PMID- 21034413 TI - Antimalarial drugs and their useful therapeutic lives: rational drug design lessons from pleiotropic action of quinolines and artemisinins. AB - Efforts to develop an effective malarial vaccine are yet to be successful and thus chemotherapy remains the mainstay of malaria control strategy. Unfortunately, Plasmodium falciparum, the parasite that causes about 90% of all global malaria cases is increasingly becoming resistant to classical antimalarials, necessitating a search for new chemotherapeutics preferably with novel modes of action. Today, rational drug discovery strategy is gaining new impetus as knowledge of malaria parasite biology expands, aided by the parasite genome database and improved bioinformatics tools. Drug development is a laborious, time consuming and costly process, and thus the "useful therapeutic lives" (UTLs) of new drugs should be commensurate with the resources invested in their development. Historical evidence on development and evolution of resistance to classical antimalarial drugs shows that the mode of action of a drug influences its UTL. Drugs that target single and specific targets such as antimalarial antifolates and atovaquone (ATQ) are rendered ineffective within a short time of their clinical use, unlike drugs with pleiotropic action such as chloroquine (CQ) and artemisinins (ART) with long UTLs. Unfortunately, almost all new targets currently being explored for development of novel drugs belong to the "specific target" other than the "multiple target" category, and is plausible that such drugs will have short UTLs. This review relates the pleiotropic action of CQ and ART with their long UTLs, and discusses their relevance in rational drug development strategies. Novel targets with potential to yield drugs with long UTLs are also explored. PMID- 21034414 TI - Exploring newer target sodium glucose transporter 2 for the treatment of diabetes mellitus. AB - Diabetes mellitus is an independent risk factor for the development of coronary artery disease, myocardial infarction, hypertension, and dyslipidemia. The treatment of diabetes has been mainly focused on maintaining normal blood glucose concentrations. Insulin and hypoglycemic agents have been used as standard therapeutic strategies. However, these are characterized by limited efficacy and adverse side effects, making the development of new therapeutic alternatives mandatory. Inhibition of glucose reabsorption in the kidney, mediated by Sodium Glucose Transporters (SGLT's), represents a promising therapeutic approach. The high-affinity sodium glucose cotransporter (SGLT1) is expressed to some extent in the kidney and contributes to glucose reabsorption, However Genetic mutations in the SGLT1 gene leading to a functional defect are responsible for glucose/galactose malabsorption. The low-affinity sodium glucose cotransporter (SGLT2), which is expressed specifically in the kidney, plays a major role in renal glucose reabsorption in the proximal tubule. We focused on SGLT2 as a molecular target for this review because it plays a major role in renal glucose reabsorption, and its tissue distribution is limited in the kidney to reduce the likelihood for mechanism-based side effects. Phlorizin, a natural phenolic O glucoside has been known to induce glucosuria for more than 100 years. As it is not a specific SGLT inhibitor, later on o-glucoside is replaced by c-glycoside as it is resistant to hydrolysis by beta-glucosidases. The present review summarizes the concept of SGLT2 selective target based therapy for diabetes mellitus and the current clinical and preclinical development of SGLT2 inhibitors. PMID- 21034415 TI - New strategies and patent therapeutics in EBV-associated diseases. AB - Epstein-Barr virus (EBV) is a virus present all throughout the world that causes infectious mononucleosis (IM) and is highly associated with certain malignancies. This study is a review of current knowledge concerning the pathogenic mechanisms of EBV in tumor and auto-immune diseases and the different new strategies to treat EBV associated pathologies. Phenomena surrounding the proliferation and immortalization of B lymphocytes, the mechanisms of immune escape and the role of CD8+ and CD4+ T cells in the infection by EBV are explained. An analysis is made of the role of EBV proteins during the biological events that take place in primary infection, persistent chronic infection together with an update of the approaches of novel patented therapeutics. Currently there is no vaccine protecting against EBV-associated disorders and no treatment that may inhibit or eliminate their progression. Thus, it is crucial to obtain additional information on the function and importance of genes that play a role on the development of those diseases with which it is associated, as well as on the humoral and cellular immune processes involved in them. PMID- 21034416 TI - Alkaloids from cyanobacteria with diverse powerful bioactivities. AB - Alkaloid containing plants represent a heterogeneous group both taxonomically and chemically, a basic nitrogen being the unifying factor for the various classes. As most alkaloids are extremely toxic, organisms containing them do not feature strongly in medicine but they have always been important in the allopathic system. Typical alkaloids are derived from plant sources, they are basic, they contain one or more nitrogen, and they usually have marked physiological actions in humans or other mammalian species. This review will present various alkaloids generated by cyanobacteria, highlighting their complex structures, powerful bioactivities, and pharmacological properties. The main groups of cyanobacterial alkaloids include the neuromuscular transmission blocker anatoxins, the ion channel blocker saxitoxins, the degenerated amino acid beta-methylamino-L alanine, the protein synthesis inhibitor guanidine alkaloid cylindrospermopsins, and cyanobacterial indol alkaloids with antiviral, antifungal, and cytotoxic activity. PMID- 21034417 TI - Target therapies in systemic lupus erythematosus: current state of the art. AB - Systemic lupus erythematosus (SLE) is a complex autoimmune disease of unknown etiology and limited available therapeutic options frustrating both clinicians and patients. However, recent advances in the understanding of disease mechanisms have given rise to numerous studies on specific approaches to SLE treatment. The purpose of this review is to explain the rationale for new treatments and results of the first clinical studies. We will focus on agents which deplete B cells (anti-CD20, anti-CD22), block cytokines (TNF alpha, Il 6), inhibit B/T cells interaction (CTLA-4Ig, anti-CD40L), or are even expected to reconstruct physiologic immunotolerance. Although preliminary results seemed promising, two randomized clinical trials with rituximab (EXPLORER and LUNAR study) failed to prove efficacy. Data analysis continues to explain the reasons. Trial design, subject population, limitations of the outcome measure instrument and site qualification have been questioned. Future studies are likely to focus on specific organ involvement or treatment combinations with other immunosuppressive agents. PMID- 21034418 TI - Endoglin-targeted cancer therapy. AB - Vascular-targeting antiangiogenic therapy (VTAT) of cancer can be advantageous over conventional tumor cell targeted cancer therapy if an appropriate target is found. Our hypothesis is that endoglin (ENG; CD105) is an excellent target in VTAT. ENG is selectively expressed on vascular and lymphatic endothelium in tumors. This allows us to target both tumor-associated vasculature and lymphatic vessels to suppress tumor growth and metastasis. ENG is essential for angiogenesis/vascular development and a co-receptor of TGF-beta. Our studies of selected anti-ENG monoclonal antibodies (mAbs) in several animal models and in vitro studies support our hypothesis. These mAbs and/or their immunoconjugates (immunotoxins and radioimmunoconjugates) induced regression of preformed tumors as well as inhibited formation of new tumors. In addition, they suppressed metastasis. Several mechanisms were involved in the suppressive activity of the naked (unconjugated) anti-ENG mAbs. These include direct growth suppression of proliferating endothelial cells, induction of apoptosis, ADCC (antibody-dependent cell-mediated cytotoxicity) and induction of T cell immunity. To facilitate clinical application, we generated a human/mouse chimeric anti-ENG mAb termed c SN6j and performed studies of pharmacokinetics, toxicology and immunogenicity of c-SN6j in nonhuman primates. No significant toxicity was detected by several criteria and minimal immune response to the murine part of c-SN6j was detected after multiple i.v. injections. The results support our hypothesis that c-SN6j can be safely administered in cancer patients. This hypothesis is supported by the ongoing phase 1 clinical trial of c-SN6j (also known as TRC105) in patients with advanced or metastatic solid cancer in collaboration with Tracon Pharma and several oncologists (NCT00582985). PMID- 21034420 TI - Emerging role of immunoPET in receptor targeted cancer therapy. AB - ImmunoPET is a non-invasive imaging technology based on tracking and quantification of radiolabeled monoclonal antibodies, antibody fragments and peptides in vivo. The knowledge of distribution and expression levels of a given receptor is a key for successful receptor targeted cancer therapy. ImmunoPET performed with probes with high affinity and specificity to a given receptor aspires to be a method for obtaining comprehensive information about current in vivo status of the targeted receptor. This review describes methods for radiolabeling of peptides, monoclonal antibodies, and antibody fragments for immunoPET and highlights the recently reported pre-clinical and clinical applications of immunoPET in receptor targeted therapy. PMID- 21034421 TI - Multifunctional nanomedicine platform for cancer specific delivery of siRNA by superparamagnetic iron oxide nanoparticles-dendrimer complexes. AB - The ability of Superparamagnetic Iron Oxide (SPIO) nanoparticles and Poly(Propyleneimine) generation 5 dendrimers (PPI G5) to cooperatively provoke siRNA complexation was investigated in order to develop a targeted, multifunctional siRNA delivery system for cancer therapy. Poly(ethylene glycol) (PEG) coating and cancer specific targeting moiety (LHRH peptide) have been incorporated into SPIO-PPI G5-siRNA complexes to enhance serum stability and selective internalization by cancer cells. Such a modification of siRNA nanoparticles enhanced its internalization into cancer cells and increased the efficiency of targeted gene suppression in vitro. Moreover, the developed siRNA delivery system was capable of sufficiently enhancing in vivo antitumor activity of an anticancer drug (Cisplatin). The proposed approach demonstrates potential for the creation of targeted multifunctional nanomedicine platforms with the ability to deliver therapeutic siRNA specifically to cancer cells in order to prevent severe adverse side effects on healthy tissues and in situ monitoring of the therapeutic outcome using clinically relevant imaging techniques. PMID- 21034422 TI - Receptor mediated tumor targeting: an emerging approach for cancer therapy. AB - Receptor-mediated tumor targeting has received major attention in the field of cancer drug delivery in the past few years. Receptors, as molecular target has opened new opportunities for cellular or intracellular targeting of drug loaded delivery systems conjugated with targeting moieties i.e. ligand. This receptor mediated targeting of cancer drug through nano carrier systems to cancerous tissue offer protection and improves the pharmacokinetics of various drugs and help to overcome the systemic toxicity and adverse effects that result from the non-selective nature of most current cancer therapeutic agents. The article reviews the scope of receptor mediated targeting of anticancer drug loaded in various nanocarriers and also summarize recent perspective and challenges in the field of nanocarrier-aided drug delivery and drug targeting for cancer therapy. PMID- 21034419 TI - Bombesin receptor-mediated imaging and cytotoxicity: review and current status. AB - The three mammalian bombesin (Bn) receptors (gastrin-releasing peptide [GRP] receptor, neuromedin B [NMB] receptor, BRS-3) are one of the classes of G protein coupled receptors that are most frequently over-express/ectopically expressed by common, important malignancies. Because of the clinical success of somatostatin receptor-mediated imaging and cytotoxicity with neuroendocrine tumors, there is now increasing interest in pursuing a similar approach with Bn receptors. In the last few years then have been more than 200 studies in this area. In the present paper, the in vitro and in vivo results, as well as results of human studies from many of these studies are reviewed and the current state of Bn receptor-mediated imaging or cytotoxicity is discussed. Both Bn receptor-mediated imaging studies as well as Bn receptor-mediated tumoral cytotoxic studies using radioactive and non-radioactive Bn-based ligands are covered. PMID- 21034424 TI - Use of analogs of peptide hormones conjugated to cytotoxic radicals for chemotherapy targeted to receptors on tumors. AB - Specific receptors for luteinizing hormone-releasing hormone (LH-RH), somatostatin, bombesin, and other peptides are found on various cancers. We review the development of cytotoxic analogs of LH-RH, somatostatin, and bombesin/gastrin releasing peptide (GRP) designed for targeting chemotherapy to peptide receptors on various cancers. Cytotoxic analogs of LH-RH, AN-152 and AN 207, containing doxorubicin (DOX) or 2-pyrrolino-DOX (AN-201), respectively, target LH-RH receptors and may be used for the treatment of prostatic and urinary bladder (urothelial), breast, ovarian and endometrial cancers, non-Hodgkin's lymphomas, melanomas, and renal cell carcinomas. DOX and AN-201 have also been incorporated into the cytotoxic analogs of somatostatin, AN-162 and AN-238, respectively, which are targeted to receptors for somatostatin in prostatic, mammary, ovarian, gastric, renal, colorectal and pancreatic cancers, non Hodgkin's lymphomas, as well as glioblastomas and lung cancers. They are found to suppress the growth of these tumors and their metastases. A cytotoxic analog of bombesin/GRP, AN-215, containing 2-pyrrolino-Dox, has also been synthesized and shown to inhibit growth of various human cancer lines expressing receptors for bombesin/GRP. The toxicity, pharmacokinetics and maximum tolerated doses of AN 152 were assessed in a phase I clinical trial in women with ovarian or endometrial cancer. Disease stabilization and objective responses were found. Analog AN-152 is now in phase II clinical trials. Phase I/II studies with AN-152 in men with hormone-independent relapsed prostate cancer and patients with pancreatic and bladder cancers are pending. Targeted cytotoxic peptide analogs could provide a more efficacious and less toxic therapy for various cancers. PMID- 21034425 TI - Somatostatin receptor-targeted anti-cancer therapy. AB - Somatostatin receptors (SSTRs), especially SSTR subtype 2, are found expressed at relatively higher levels in many tumor cells and in tumoral blood vessels relative to normal tissues. This creates an opportunity for developing various cytotoxic SST conjugates that selectively target SSTR2-specific sites. Accordingly, some potent chemotherapeutic agents such as camptothecin (CPT), methotrexate (MTX), paclitaxel (PTX) and doxorubicin (DOX) have been coupled to SSTR2-preferential somatostatin (SST) analogs. These new cytotoxic SST conjugates display significant SSTR-selective anti-tumor abilities in many different types of tumors. For instance, the CPT-SST conjugate JF-10-81, in which CPT is coupled to the N-terminus of a SSTR2-specific SST analog (JF-07-69), had wide ranging anti-tumor and anti-angiogenic ability. This conjugate also showed an ability to overcome multi-drug resistance (MDR) in SSTR-over-expressing and CPT-insensitive human pancreatic carcinoid BON cells. Notably, another DOX-SST conjugate, AN-238, made by coupling pyrrolino-DOX to the SST analog RC-121, displayed indirect anti tumor activity against SSTR-negative, non-small cell lung cancer H-157 tumor growth by directly targeting SSTR-positive tumoral vessels of host mice. These cytotoxic SST conjugates should deliver chemotherapeutic agents to receptor specific sites, enhance anti-tumor efficacy, reduce toxic side effects to normal tissues, and to some extent, overcome MDR. These and other peptide conjugates may possibly represent a newer generation of receptor-targeted cancer therapeutics. This review discusses the progress with reference to SST-based and SSTR-selective cytotoxic cancer therapy. PMID- 21034423 TI - Radioimmunotherapy of solid tumors: searching for the right target. AB - Radioimmunotherapy of solid tumors remains a challenge despite the tremendous success of 90Y ibritumomab tiuxetan (Zevalin) and 131I Tositumomab (Bexxar) in treating non-Hodgkin's lymphoma. For a variety of reasons, clinical trials of radiolabeled antibodies against solid tumors have not led to responses equivalent to those seen against lymphoma. In contrast, promising responses have been observed with unlabeled antibodies that target solid tumor receptors associated with cellular signaling pathways. These observations suggest that anti-tumor efficacy of the carrier antibody might be critical to achieving clinical responses. Here, we review and compare tumor antigens targeted by radiolabeled antibodies and unlabeled antibodies used in immunotherapy. The review shows that the trend for radiolabeled antibodies under pre-clinical development is to also target antigens associated with signaling pathways that are essential for the growth and survival of the tumor. PMID- 21034426 TI - Efficient motif finding algorithms for large-alphabet inputs. AB - BACKGROUND: We consider the problem of identifying motifs, recurring or conserved patterns, in the biological sequence data sets. To solve this task, we present a new deterministic algorithm for finding patterns that are embedded as exact or inexact instances in all or most of the input strings. RESULTS: The proposed algorithm (1) improves search efficiency compared to existing algorithms, and (2) scales well with the size of alphabet. On a synthetic planted DNA motif finding problem our algorithm is over 10* more efficient than MITRA, PMSPrune, and RISOTTO for long motifs. Improvements are orders of magnitude higher in the same setting with large alphabets. On benchmark TF-binding site problems (FNP, CRP, LexA) we observed reduction in running time of over 12*, with high detection accuracy. The algorithm was also successful in rapidly identifying protein motifs in Lipocalin, Zinc metallopeptidase, and supersecondary structure motifs for Cadherin and Immunoglobin families. CONCLUSIONS: Our algorithm reduces computational complexity of the current motif finding algorithms and demonstrate strong running time improvements over existing exact algorithms, especially in important and difficult cases of large-alphabet sequences. PMID- 21034427 TI - Graphical models for inferring single molecule dynamics. AB - BACKGROUND: The recent explosion of experimental techniques in single molecule biophysics has generated a variety of novel time series data requiring equally novel computational tools for analysis and inference. This article describes in general terms how graphical modeling may be used to learn from biophysical time series data using the variational Bayesian expectation maximization algorithm (VBEM). The discussion is illustrated by the example of single-molecule fluorescence resonance energy transfer (smFRET) versus time data, where the smFRET time series is modeled as a hidden Markov model (HMM) with Gaussian observables. A detailed description of smFRET is provided as well. RESULTS: The VBEM algorithm returns the model's evidence and an approximating posterior parameter distribution given the data. The former provides a metric for model selection via maximum evidence (ME), and the latter a description of the model's parameters learned from the data. ME/VBEM provide several advantages over the more commonly used approach of maximum likelihood (ML) optimized by the expectation maximization (EM) algorithm, the most important being a natural form of model selection and a well-posed (non-divergent) optimization problem. CONCLUSIONS: The results demonstrate the utility of graphical modeling for inference of dynamic processes in single molecule biophysics. PMID- 21034428 TI - A machine learning pipeline for quantitative phenotype prediction from genotype data. AB - BACKGROUND: Quantitative phenotypes emerge everywhere in systems biology and biomedicine due to a direct interest for quantitative traits, or to high individual variability that makes hard or impossible to classify samples into distinct categories, often the case with complex common diseases. Machine learning approaches to genotype-phenotype mapping may significantly improve Genome-Wide Association Studies (GWAS) results by explicitly focusing on predictivity and optimal feature selection in a multivariate setting. It is however essential that stringent and well documented Data Analysis Protocols (DAP) are used to control sources of variability and ensure reproducibility of results. We present a genome-to-phenotype pipeline of machine learning modules for quantitative phenotype prediction. The pipeline can be applied for the direct use of whole-genome information in functional studies. As a realistic example, the problem of fitting complex phenotypic traits in heterogeneous stock mice from single nucleotide polymorphims (SNPs) is here considered. METHODS: The core element in the pipeline is the L1L2 regularization method based on the naive elastic net. The method gives at the same time a regression model and a dimensionality reduction procedure suitable for correlated features. Model and SNP markers are selected through a DAP originally developed in the MAQC-II collaborative initiative of the U.S. FDA for the identification of clinical biomarkers from microarray data. The L1L2 approach is compared with standard Support Vector Regression (SVR) and with Recursive Jump Monte Carlo Markov Chain (MCMC). Algebraic indicators of stability of partial lists are used for model selection; the final panel of markers is obtained by a procedure at the chromosome scale, termed 'saturation', to recover SNPs in Linkage Disequilibrium with those selected. RESULTS: With respect to both MCMC and SVR, comparable accuracies are obtained by the L1L2 pipeline. Good agreement is also found between SNPs selected by the L1L2 algorithms and candidate loci previously identified by a standard GWAS. The combination of L1L2-based feature selection with a saturation procedure tackles the issue of neglecting highly correlated features that affects many feature selection algorithms. CONCLUSIONS: The L1L2 pipeline has proven effective in terms of marker selection and prediction accuracy. This study indicates that machine learning techniques may support quantitative phenotype prediction, provided that adequate DAPs are employed to control bias in model selection. PMID- 21034429 TI - Classifying and scoring of molecules with the NGN: new datasets, significance tests, and generalization. AB - This paper demonstrates how a Neural Grammar Network learns to classify and score molecules for a variety of tasks in chemistry and toxicology. In addition to a more detailed analysis on datasets previously studied, we introduce three new datasets (BBB, FXa, and toxicology) to show the generality of the approach. A new experimental methodology is developed and applied to both the new datasets as well as previously studied datasets. This methodology is rigorous and statistically grounded, and ultimately culminates in a Wilcoxon significance test that proves the effectiveness of the system. We further include a complete generalization of the specific technique to arbitrary grammars and datasets using a mathematical abstraction that allows researchers in different domains to apply the method to their own work. BACKGROUND: Our work can be viewed as an alternative to existing methods to solve the quantitative structure-activity relationship (QSAR) problem. To this end, we review a number approaches both from a methodological and also a performance perspective. In addition to these approaches, we also examined a number of chemical properties that can be used by generic classifier systems, such as feed-forward artificial neural networks. In studying these approaches, we identified a set of interesting benchmark problem sets to which many of the above approaches had been applied. These included: ACE, AChE, AR, BBB, BZR, Cox2, DHFR, ER, FXa, GPB, Therm, and Thr. Finally, we developed our own benchmark set by collecting data on toxicology. RESULTS: Our results show that our system performs better than, or comparatively to, the existing methods over a broad range of problem types. Our method does not require the expert knowledge that is necessary to apply the other methods to novel problems. CONCLUSIONS: We conclude that our success is due to the ability of our system to: 1) encode molecules losslessly before presentation to the learning system, and 2) leverage the design of molecular description languages to facilitate the identification of relevant structural attributes of the molecules over different problem domains. PMID- 21034430 TI - Inferring latent task structure for Multitask Learning by Multiple Kernel Learning. AB - BACKGROUND: The lack of sufficient training data is the limiting factor for many Machine Learning applications in Computational Biology. If data is available for several different but related problem domains, Multitask Learning algorithms can be used to learn a model based on all available information. In Bioinformatics, many problems can be cast into the Multitask Learning scenario by incorporating data from several organisms. However, combining information from several tasks requires careful consideration of the degree of similarity between tasks. Our proposed method simultaneously learns or refines the similarity between tasks along with the Multitask Learning classifier. This is done by formulating the Multitask Learning problem as Multiple Kernel Learning, using the recently published q-Norm MKL algorithm. RESULTS: We demonstrate the performance of our method on two problems from Computational Biology. First, we show that our method is able to improve performance on a splice site dataset with given hierarchical task structure by refining the task relationships. Second, we consider an MHC-I dataset, for which we assume no knowledge about the degree of task relatedness. Here, we are able to learn the task similarities ab initio along with the Multitask classifiers. In both cases, we outperform baseline methods that we compare against. CONCLUSIONS: We present a novel approach to Multitask Learning that is capable of learning task similarity along with the classifiers. The framework is very general as it allows to incorporate prior knowledge about tasks relationships if available, but is also able to identify task similarities in absence of such prior information. Both variants show promising results in applications from Computational Biology. PMID- 21034431 TI - Semi-supervised prediction of protein subcellular localization using abstraction augmented Markov models. AB - BACKGROUND: Determination of protein subcellular localization plays an important role in understanding protein function. Knowledge of the subcellular localization is also essential for genome annotation and drug discovery. Supervised machine learning methods for predicting the localization of a protein in a cell rely on the availability of large amounts of labeled data. However, because of the high cost and effort involved in labeling the data, the amount of labeled data is quite small compared to the amount of unlabeled data. Hence, there is a growing interest in developing semi-supervised methods for predicting protein subcellular localization from large amounts of unlabeled data together with small amounts of labeled data. RESULTS: In this paper, we present an Abstraction Augmented Markov Model (AAMM) based approach to semi-supervised protein subcellular localization prediction problem. We investigate the effectiveness of AAMMs in exploiting unlabeled data. We compare semi-supervised AAMMs with: (i) Markov models (MMs) (which do not take advantage of unlabeled data); (ii) an expectation maximization (EM); and (iii) a co-training based approaches to semi-supervised training of MMs (that make use of unlabeled data). CONCLUSIONS: The results of our experiments on three protein subcellular localization data sets show that semi-supervised AAMMs: (i) can effectively exploit unlabeled data; (ii) are more accurate than both the MMs and the EM based semi-supervised MMs; and (iii) are comparable in performance, and in some cases outperform, the co-training based semi-supervised MMs. PMID- 21034432 TI - Exploiting physico-chemical properties in string kernels. AB - BACKGROUND: String kernels are commonly used for the classification of biological sequences, nucleotide as well as amino acid sequences. Although string kernels are already very powerful, when it comes to amino acids they have a major short coming. They ignore an important piece of information when comparing amino acids: the physico-chemical properties such as size, hydrophobicity, or charge. This information is very valuable, especially when training data is less abundant. There have been only very few approaches so far that aim at combining these two ideas. RESULTS: We propose new string kernels that combine the benefits of physico-chemical descriptors for amino acids with the ones of string kernels. The benefits of the proposed kernels are assessed on two problems: MHC-peptide binding classification using position specific kernels and protein classification based on the substring spectrum of the sequences. Our experiments demonstrate that the incorporation of amino acid properties in string kernels yields improved performances compared to standard string kernels and to previously proposed non substring kernels. CONCLUSIONS: In summary, the proposed modifications, in particular the combination with the RBF substring kernel, consistently yield improvements without affecting the computational complexity. The proposed kernels therefore appear to be the kernels of choice for any protein sequence-based inference. AVAILABILITY: Data sets, code and additional information are available from http://www.fml.tuebingen.mpg.de/raetsch/suppl/aask. Implementations of the developed kernels are available as part of the Shogun toolbox. PMID- 21034433 TI - Infinite mixture-of-experts model for sparse survival regression with application to breast cancer. AB - BACKGROUND: We present an infinite mixture-of-experts model to find an unknown number of sub-groups within a given patient cohort based on survival analysis. The effect of patient features on survival is modeled using the Cox's proportionality hazards model which yields a non-standard regression component. The model is able to find key explanatory factors (chosen from main effects and higher-order interactions) for each sub-group by enforcing sparsity on the regression coefficients via the Bayesian Group-Lasso. RESULTS: Simulated examples justify the need of such an elaborate framework for identifying sub-groups along with their key characteristics versus other simpler models. When applied to a breast-cancer dataset consisting of survival times and protein expression levels of patients, it results in identifying two distinct sub-groups with different survival patterns (low-risk and high-risk) along with the respective sets of compound markers. CONCLUSIONS: The unified framework presented here, combining elements of cluster and feature detection for survival analysis, is clearly a powerful tool for analyzing survival patterns within a patient group. The model also demonstrates the feasibility of analyzing complex interactions which can contribute to definition of novel prognostic compound markers. PMID- 21034434 TI - Can choices between alternative hip prostheses be evidence based? a review of the economic evaluation literature. AB - BACKGROUND: Total hip replacement surgery places a considerable financial burden on health services and society. Given the large number of hip prostheses available to surgeons, reliable economic evidence is crucial to inform resource allocation decisions. This review summarises published economic evidence on alternative hip prostheses to examine the potential for the literature to inform resource allocation decisions in the UK. METHODS: We searched nine medical and economics electronic databases. 3,270 studies were initially identified, 17 studies were included in the review. Studies were critically appraised using three separate guidelines. RESULTS: Several methodological problems were identified including a lack of observed long term prosthesis survival data, limited up-to-date and UK based evidence and exclusion of patient and societal perspectives. CONCLUSIONS: More clinical trials including long term follow-up and economic evaluation are needed. These should compare the cost-effectiveness of different prostheses with longer-term follow-up and including a wider perspective. PMID- 21034435 TI - Adiponectin promotes syncytialisation of BeWo cell line and primary trophoblast cells. AB - BACKGROUND: In human pregnancy, a correct placentation depends on trophoblast proliferation, differentiation, migration and invasion. These processes are highly regulated by placental hormones, growth factors and cytokines. Recently, we have shown that adiponectin, an adipokine, has anti-proliferative effects on trophoblastic cells. Here, we complete this study by demonstrating that adiponectin modulates BeWo and human villous cytotrophoblast cell differentiation. RESULTS: We showed that hCG secretion was up-regulated by adiponectin treatment in both BeWo cells and human cytotrophoblasts from very early placentas (5-6 weeks). The expression of two trophoblast differentiation markers, leptin and syncytin 2, was also up-regulated by adiponectin in BeWo cells. Moreover, adiponectin treatment induced a loss of E-cadherin staining in these cells. In parallel, we demonstrated that AdipoR1 and AdipoR2 are up regulated during forskolin induced BeWo cell differentiation, reinforcing the role of adiponectin in trophoblast syncytialization. SiRNA mediated down regulation of AdipoR1 and AdipoR2 was used to demonstrate that adiponectin effects on differentiation were essentially mediated by these receptors. Finally, using a specific inhibitor, we demonstrated that the PKA signalling pathway could be one pathway involved in adiponectin effects on trophoblast differentiation. CONCLUSION: Adiponectin enhances the differentiation process of trophoblast cells and could thus be involved in functional syncytiotrophoblast formation. PMID- 21034437 TI - Population screening for hereditary and familial cancer syndromes in Valka district of Latvia. AB - BACKGROUND: The growing possibilities of cancer prevention and treatment as well as the increasing knowledge about hereditary cancers require proper identification of the persons at risk. The aim of this study was to test the outcome of population screening in the scientific and practical evaluation of hereditary cancer. METHODS: Population screening for hereditary cancer was carried out retrospectively in a geographic area of Latvia. Family cancer histories were collected from 18642 adults representing 76.6% of the population of this area. Hereditary cancer syndromes were diagnosed clinically. Molecular testing for BRCA1 founder mutations 300 T/G, 4153delA and 5382insC was conducted in 588 persons who reported at least one case of breast or ovary cancer among blood relatives. RESULTS: Clinically, 74 (0.40%; 95% confidence interval (CI): 0.32 - 0.50%) high-risk and 548 (2.94%, 95% CI: 2.71 - 3.19) moderate-risk hereditary cancer syndromes were detected covering wide cancer spectrum. All syndromes were characterised by high cancer frequency among blood relatives ranging 8.6 - 46.2% in contrast to spouse correlation of 2.5 - 3.6%. The mean age of cancer onset ranged 38.0 - 72.0 years in different syndromes. The BRCA1 gene mutations were identified in 10 (1.7%; 95% CI: 0.9 - 3.1%) probands. Families with established BRCA1 gene founder mutations were identified with the frequency 1:2663 clinically screened persons. CONCLUSIONS: Population screening is a useful practical tool for the identification of persons belonging to families with high frequency of malignant tumours. The whole hereditary and familial cancer spectrum along with the age structure was identified adjusting follow-up guidelines. Another benefit of the population screening is the possibility to identify oncologically healthy persons belonging to hereditary and familial cancer families so that appropriate surveillance can be offered. Clinical diagnostics is appropriate for population screening purposes; molecular investigation provides additional information. In collaboration with family doctors, the screening is technically manageable as characterised by high compliance. PMID- 21034436 TI - Effects of olive oil and its fractions on oxidative stress and the liver's fatty acid composition in 2,4-Dichlorophenoxyacetic acid-treated rats. AB - BACKGROUND: Olive oil's beneficial effects are not only related to its high content of oleic acid, but also to the antioxidant potential of its polyphenols. In this study, we assess the effects of virgin olive oil and its fractions on 2,4 D- induced oxidative damage in the liver of rats. METHODS: Male Wistar rats were randomly divided into eight groups of ten each: (C) a control group, (D) group that received 2,4-D (5 mg/kg b.w.), (D/EVOO) group treated with 2,4-D plus extra virgin olive oil, (D/OOHF) group that received 2,4-D plus hydrophilic fraction, (D/OOLF) group treated with 2,4-D plus lipophilic fraction, (EVOO) group that received only extra virgin olive oil, (OOHF) group given hydrophilic fraction and (OOLF) group treated with lipophilic fraction. These components were daily administered by gavage for 4 weeks. RESULTS: A significant liver damage was observed in rats treated with 2,4-D via increased serum levels of transaminases and alkaline phosphatase, hepatic lipid peroxidation and decreased hepatic antioxidant enzyme activities, namely, superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase. The liver's fatty acid composition was also significantly modified with 2,4-D exposure. However, extra virgin olive oil and hydrophilic fraction intake during 2,4-D treatment induced a significant increase in the antioxidant enzyme activities and a decrease in the conjugated dienes (CD) and thiobarbituric acid-reactive substances (TBARs) levels in the liver. The lipophilic fraction supplemented to 2,4-D- treated rats did not show any improvement in the liver oxidative status while a marked improvement was detected in the hepatic fatty acid composition of rats supplemented with olive oil and the two fractions. CONCLUSION: We concluded that the protective effect of olive oil against oxidative damage induced by 2,4-D is mainly related to the antioxidant potential of its hydrophilic fraction. PMID- 21034438 TI - Patients' functioning as predictor of nursing workload in acute hospital units providing rehabilitation care: a multi-centre cohort study. AB - BACKGROUND: Management decisions regarding quality and quantity of nurse staffing have important consequences for hospital budgets. Furthermore, these management decisions must address the nursing care requirements of the particular patients within an organizational unit. In order to determine optimal nurse staffing needs, the extent of nursing workload must first be known. Nursing workload is largely a function of the composite of the patients' individual health status, particularly with respect to functioning status, individual need for nursing care, and severity of symptoms. The International Classification of Functioning, Disability and Health (ICF) and the derived subsets, the so-called ICF Core Sets, are a standardized approach to describe patients' functioning status. The objectives of this study were to (1) examine the association between patients' functioning, as encoded by categories of the Acute ICF Core Sets, and nursing workload in patients in the acute care situation, (2) compare the variance in nursing workload explained by the ICF Core Set categories and with the Barthel Index, and (3) validate the Acute ICF Core Sets by their ability to predict nursing workload. METHODS: Patients' functioning at admission was assessed using the respective Acute ICF Core Set and the Barthel Index, whereas nursing workload data was collected using an established instrument. Associations between dependent and independent variables were modelled using linear regression. Variable selection was carried out using penalized regression. RESULTS: In patients with neurological and cardiopulmonary conditions, selected ICF categories and the Barthel Index Score explained the same variance in nursing workload (44% in neurological conditions, 35% in cardiopulmonary conditions), whereas ICF was slightly superior to Barthel Index Score for musculoskeletal conditions (20% versus 16%). CONCLUSIONS: A substantial fraction of the variance in nursing workload in patients with rehabilitation needs in the acute hospital could be predicted by selected categories of the Acute ICF Core Sets, or by the Barthel Index score. Incorporating ICF Core Set-based data in nursing management decisions, particularly staffing decisions, may be beneficial. PMID- 21034439 TI - Willingness to accept H1N1 pandemic influenza vaccine: a cross-sectional study of Hong Kong community nurses. AB - BACKGROUND: The 2009 pandemic of influenza A (H1N1) infection has alerted many governments to make preparedness plan to control the spread of influenza A (H1N1) infection. Vaccination for influenza is one of the most important primary preventative measures to reduce the disease burden. Our study aims to assess the willingness of nurses who work for the community nursing service (CNS) in Hong Kong on their acceptance of influenza A (H1N1) influenza vaccination. METHODS: 401 questionnaires were posted from June 24, 2009 to June 30, 2009 to community nurses with 67% response rate. Results of the 267 respondents on their willingness to accept influenza A (H1N1) vaccine were analyzed. RESULTS: Twenty seven percent of respondents were willing to accept influenza vaccination if vaccines were available. Having been vaccinated for seasonable influenza in the previous 12 months were significantly independently associated with their willingness to accept influenza A (H1N1) vaccination (OR = 4.03; 95% CI: 2.03 7.98). CONCLUSIONS: Similar to previous findings conducted in hospital healthcare workers and nurses, we confirmed that the willingness of community nurses to accept influenza A (H1N1) vaccination is low. Future studies that evaluate interventions to address nurses' specific concerns or interventions that aim to raise the awareness among nurses on the importance of influenza A (H1N1) vaccination to protect vulnerable patient populations is needed. PMID- 21034440 TI - Predicting direct protein interactions from affinity purification mass spectrometry data. AB - BACKGROUND: Affinity purification followed by mass spectrometry identification (AP-MS) is an increasingly popular approach to observe protein-protein interactions (PPI) in vivo. One drawback of AP-MS, however, is that it is prone to detecting indirect interactions mixed with direct physical interactions. Therefore, the ability to distinguish direct interactions from indirect ones is of much interest. RESULTS: We first propose a simple probabilistic model for the interactions captured by AP-MS experiments, under which the problem of separating direct interactions from indirect ones is formulated. Then, given idealized quantitative AP-MS data, we study the problem of identifying the most likely set of direct interactions that produced the observed data. We address this challenging graph theoretical problem by first characterizing signatures that can identify weakly connected nodes as well as dense regions of the network. The rest of the direct PPI network is then inferred using a genetic algorithm.Our algorithm shows good performance on both simulated and biological networks with very high sensitivity and specificity. Then the algorithm is used to predict direct interactions from a set of AP-MS PPI data from yeast, and its performance is measured against a high-quality interaction dataset. CONCLUSIONS: As the sensitivity of AP-MS pipeline improves, the fraction of indirect interactions detected will also increase, thereby making the ability to distinguish them even more desirable. Despite the simplicity of our model for indirect interactions, our method provides a good performance on the test networks. PMID- 21034441 TI - Clinicopathological characteristics of resected adenosquamous cell carcinoma of the lung: risk of coexistent double cancer. AB - BACKGROUND: adenosquamous carcinoma (ADSQ) of non-small cell lung cancer (NSCLC) is a rare disease and the biological behavior and clinicopathological characteristics have not yet been thoroughly described. METHOD: This study reviewed the patient charts of 11 (1.6%) ADSQ cases among 779 patients with primary lung cancer who underwent a lung resection. The characteristics and clinicopathological factors were evaluated retrospectively. RESULTS: Six of the 11 patients with ADSQ were male and five were female. The mean age was 67.3 years' olds. Three patients had pathological stage IA, one patient each had stage IB and IIA, five patients had stage IIIA, and one patient stage IIIB. Five patients had coexistent double cancer including 2 gastric, 1 rectal, 1 prostate and 1 bladder cancer. ADSQ was found less frequently in males than squamous cell carcinoma (SQ). ADSQ was found more frequently in older patients, with advanced stage, advanced T status, and lymph node metastases than adenocarcinoma (AD). The proportion with coexistent double cancer of AD, SQ, and ADSQ were 21.1, 17.6, and 45.5%, respectively. ADSQ had a significantly correlation with double cancer (ADSQ vs. non- ADSQ p = 0.03). A multivariate analysis showed no significant prognostic difference between the patients with ADSQ and non- ADSQ. CONCLUSIONS: In this study, cases with ADSQ showed no significantly prognostic difference in comparison to AD and SQ. However, surgeons must be cautious of any coexistent double cancer because approximately half of all patients with ADSQ of the lung have double cancer. PMID- 21034442 TI - Development of a real-time quantitative PCR assay for detection of a stable genomic region of BK virus. AB - BACKGROUND: BK virus infections can have clinically significant consequences in immunocompromised individuals. Detection and monitoring of active BK virus infections in certain situations is recommended and therefore PCR assays for detection of BK virus have been developed. The performance of current BK PCR detection assays is limited by the existence of viral polymorphisms, unknown at the time of assay development, resulting in inconsistent detection of BK virus. The objective of this study was to identify a stable region of the BK viral genome for detection by PCR that would be minimally affected by polymorphisms as more sequence data for BK virus becomes available. RESULTS: Employing a combination of techniques, including amino acid and DNA sequence alignment and interspecies analysis, a conserved, stable PCR target region of the BK viral genomic region was identified within the VP2 gene. A real-time quantitative PCR assay was then developed that is specific for BK virus, has an analytical sensitivity of 15 copies/reaction (450 copies/ml) and is highly reproducible (CV <= 5.0%). CONCLUSION: Identifying stable PCR target regions when limited DNA sequence data is available may be possible by combining multiple analysis techniques to elucidate potential functional constraints on genomic regions. Applying this approach to the development of a real-time quantitative PCR assay for BK virus resulted in an accurate method with potential clinical applications and advantages over existing BK assays. PMID- 21034443 TI - The nucleotide addition cycle of RNA polymerase is controlled by two molecular hinges in the Bridge Helix domain. AB - BACKGROUND: Cellular RNA polymerases (RNAPs) are complex molecular machines that combine catalysis with concerted conformational changes in the active center. Previous work showed that kinking of a hinge region near the C-terminus of the Bridge Helix (BH-H(C)) plays a critical role in controlling the catalytic rate. RESULTS: Here, new evidence for the existence of an additional hinge region in the amino-terminal portion of the Bridge Helix domain (BH-H(N)) is presented. The nanomechanical properties of BH-H(N) emerge as a direct consequence of the highly conserved primary amino acid sequence. Mutations that are predicted to influence its flexibility cause corresponding changes in the rate of the nucleotide addition cycle (NAC). BH-H(N) displays functional properties that are distinct from BH-H(C), suggesting that conformational changes in the Bridge Helix control the NAC via two independent mechanisms. CONCLUSIONS: The properties of two distinct molecular hinges in the Bridge Helix of RNAP determine the functional contribution of this domain to key stages of the NAC by coordinating conformational changes in surrounding domains. PMID- 21034444 TI - Letter to the editor. Re:. Initial experience with a synthetic sealant PleuraSealTM after pulmonary resections: a prospective study with retrospective case matched controls. AB - A response to Dango S, Lin R, Hennings E, Passlick B. Initial experience with a synthetic sealant PleuraSealTM after pulmonary resections: a prospective study with retrospective case matched controls. Journal of Cardiothoracic Surgery 2010, 5:50. PMID- 21034445 TI - Occult pneumothorax, revisited. AB - Pneumothorax is a recognized cause of preventable death following chest wall trauma where a simple intervention can be life saving. In cases of trauma patients where cervical spine immobilization is mandatory, supine AP chest radiograph is the most practical initial study. It is however not as sensitive as CT chest for early detection of a pneumothorax. "Occult" pneumothorax is an accepted definition of an existing but usually a clinically and radiologically silent disturbance that in most patients can be tolerated while other more urgent trauma needs are attended to. However, in certain patients, especially those on mechanical ventilation (with subsequent increase of intrapleural air with positive pressure ventilation), missing the diagnosis of pneumothorax can be deleterious with fatal consequences. This review will discuss the occult pneumothorax in the context of 3 radiological examples, which will further emphasize the entity. Because a negative AP chest radiograph can dangerously delay its recognition, we recommend that any trauma victim presenting to the emergency department with symptoms of respiratory distress should be screened with either thoracic ultrasonography or chest CT scan to avoid missing a pneumothorax. PMID- 21034446 TI - A possible new syndrome with double endocrine tumors in association with an unprecedented type of familial heart-hand syndrome: a case report. AB - INTRODUCTION: The combination of a pituitary prolactinoma and an aldosterone producing adrenal adenoma is extremely rare. To the best of our knowledge, double endocrine tumors in association with heart-hand syndrome have not previously been reported. CASE PRESENTATION: A 21-year-old Japanese woman presented with galactorrhea and decreased visual acuity. A large pituitary adenoma with an increased level of serum prolactin was apparent by computed tomography. She additionally showed mild hypertension (136/90 mmHg) accompanied by hypokalemia. The plasma aldosterone concentration was increased. Computed tomography showed a mass in the right adrenal gland. No other tumors were found despite extensive imaging studies. Physical and radiographic examinations showed skeletal malformations of the hands and feet, including hypoplasia of the first digit in all four limbs. An atrial septal defect was demonstrated by echocardiography. Similar digital and cardiac abnormalities were detected in our patient's father, and a clinical diagnosis of hereditary heart-hand syndrome was made. CONCLUSION: No established heart-hand syndrome was wholly compatible with the family's phenotype. Her father had no obvious endocrine tumors, implying that the parent of transmission determined variable phenotypic expression of the disease: heart hand syndrome with multiple endocrine tumors from the paternal transmission or no endocrine tumor from the maternal transmission. This suggests that the gene or genes responsible for the disease may be under tissue-specific imprinting control. PMID- 21034448 TI - Smoking-mediated up-regulation of GAD67 expression in the human airway epithelium. AB - BACKGROUND: The production of gamma-amino butyric acid (GABA) is dependent on glutamate decarboxylases (GAD65 and GAD67), the enzymes that catalyze the decarboxylation of glutamate to GABA. Based on studies suggesting a role of the airway epithelial GABAergic system in asthma-related mucus overproduction, we hypothesized that cigarette smoking, another disorder associated with increased mucus production, may modulate GABAergic system-related gene expression levels in the airway epithelium. METHODS: We assessed expression of the GABAergic system in human airway epithelium obtained using bronchoscopy to sample the epithelium and microarrays to evaluate gene expression. RT-PCR was used to confirm gene expression of GABAergic system gene in large and small airway epithelium from heathy nonsmokers and healthy smokers. The differences in the GABAergic system gene was further confirmed by TaqMan, immunohistochemistry and Western analysis. RESULTS: The data demonstrate there is a complete GABAergic system expressed in the large and small human airway epithelium, including glutamate decarboxylase, GABA receptors, transporters and catabolism enzymes. Interestingly, of the entire GABAergic system, smoking modified only the expression of GAD67, with marked up regulation of GAD67 gene expression in both large (4.1-fold increase, p < 0.01) and small airway epithelium of healthy smokers (6.3-fold increase, p < 0.01). At the protein level, Western analysis confirmed the increased expression of GAD67 in airway epithelium of healthy smokers compared to healthy nonsmokers (p < 0.05). There was a significant positive correlation between GAD67 and MUC5AC gene expression in both large and small airway epithelium (p < 0.01), implying a link between GAD67 and mucin overproduction in association with smoking. CONCLUSIONS: In the context that GAD67 is the rate limiting enzyme in GABA synthesis, the correlation of GAD67 gene expression with MUC5AC expressions suggests that the up regulation of airway epithelium expression of GAD67 may contribute to the increase in mucus production observed in association with cigarette smoking. TRIAL REGISTRATION: NCT00224198; NCT00224185. PMID- 21034447 TI - Long-acting beta-agonists in the management of chronic obstructive pulmonary disease: current and future agents. AB - Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow limitation and debilitating symptoms. For patients with moderate-to severe COPD, long-acting bronchodilators are the mainstay of therapy; as symptoms progress, guidelines recommend combining bronchodilators from different classes to improve efficacy. Inhaled long-acting beta2-agonists (LABAs) have been licensed for the treatment of COPD since the late 1990s and include formoterol and salmeterol. They improve lung function, symptoms of breathlessness and exercise limitation, health-related quality of life, and may reduce the rate of exacerbations, although not all patients achieve clinically meaningful improvements in symptoms or health related quality of life. In addition, LABAs have an acceptable safety profile, and are not associated with an increased risk of respiratory mortality, although adverse effects such as palpitations and tremor may limit the dose that can be tolerated. Formoterol and salmeterol have 12-hour durations of action; however, sustained bronchodilation is desirable in COPD. A LABA with a 24-hour duration of action could provide improvements in efficacy, compared with twice-daily LABAs, and the once-daily dosing regimen could help improve compliance. It is also desirable that a new LABA should demonstrate fast onset of action, and a safety profile at least comparable to existing LABAs.A number of novel LABAs with once-daily profiles are in development which may be judged against these criteria. Indacaterol, a LABA with a 24-hour duration of bronchodilation and fast onset of action, is the most advanced of these. Preliminary results from large clinical trials suggest indacaterol improves lung function compared with placebo and other long-acting bronchodilators. Other LABAs with a 24-hour duration of bronchodilation include carmoterol, vilanterol trifenatate and oldaterol, with early results indicating potential for once-daily dosing in humans.The introduction of once-daily LABAs also provides the opportunity to develop combination inhalers of two or more classes of once-daily long-acting bronchodilators, which may be advantageous for COPD patients through simplification of treatment regimens as well as improvements in efficacy. Once-daily LABAs used both alone and in combination with long-acting muscarinic antagonists represent a promising advance in the treatment of COPD, and are likely to further improve outcomes for patients. PMID- 21034449 TI - Systemic markers of inflammation are independently associated with S100B concentration: results of an observational study in subjects with acute ischaemic stroke. AB - BACKGROUND: Vascular dysfunction and brain inflammation are thought to contribute to the pathophysiology of cerebral injury in acute stroke. However acute inflammation and vascular dysfunction may simply be markers of an acute phase response to cerebral injury, reflecting the size of the cerebral lesion. We aimed to determine if systemic markers of vascular dysfunction and inflammation are independently associated with concentrations of the astroglial protein S100B, a marker of brain injury, in participants with acute ischaemic stroke. METHODS: Fifty-seven men and women recruited within 96 hours of acute ischaemic stroke at two tertiary hospitals participated in this cross sectional observational study. Clinical, imaging (stroke lesions area measured with perfusion CT) and laboratory data were the independent variables and co-variates. The outcome variable was serum S100B concentration, analysed by multivariate regression. RESULTS: High sensitivity-CRP (B = 0.41) and lesion area (B = 0.69) were independently associated with S100B concentration (R2 = 0.75, p < 0.01). Other variables with significant univariate associations with S100B concentration were not independently associated with S100B concentration in the final multivariate model. CONCLUSION: The degree of systemic inflammation is associated with S100B concentration in acute ischaemic stroke, independent of the size of the ischaemic lesion. PMID- 21034450 TI - Coronary artery surgery in a man with achondroplasia: a case report. AB - INTRODUCTION: Achondroplasia is a musculoskeletal disorder associated with short stature. Despite an estimated prevalence of 1:25,000 in the general population, there is little literature concerning the diagnostic and treatment challenges faced by doctors dealing with a heart operation on a patient with this condition. CASE PRESENTATION: We present the case of a 41-year-old Caucasian man of Greek ethnicity with achondroplasia, who underwent bypass heart surgery. CONCLUSIONS: The surgery was successful and did not present particular difficulties, showing that heart surgery can be safely performed on people with achondroplasia. PMID- 21034451 TI - Penalized likelihood and multi-objective spatial scans for the detection and inference of irregular clusters. AB - BACKGROUND: Irregularly shaped spatial clusters are difficult to delineate. A cluster found by an algorithm often spreads through large portions of the map, impacting its geographical meaning. Penalized likelihood methods for Kulldorff's spatial scan statistics have been used to control the excessive freedom of the shape of clusters. Penalty functions based on cluster geometry and non connectivity have been proposed recently. Another approach involves the use of a multi-objective algorithm to maximize two objectives: the spatial scan statistics and the geometric penalty function. RESULTS & DISCUSSION: We present a novel scan statistic algorithm employing a function based on the graph topology to penalize the presence of under-populated disconnection nodes in candidate clusters, the disconnection nodes cohesion function. A disconnection node is defined as a region within a cluster, such that its removal disconnects the cluster. By applying this function, the most geographically meaningful clusters are sifted through the immense set of possible irregularly shaped candidate cluster solutions. To evaluate the statistical significance of solutions for multi objective scans, a statistical approach based on the concept of attainment function is used. In this paper we compared different penalized likelihoods employing the geometric and non-connectivity regularity functions and the novel disconnection nodes cohesion function. We also build multi-objective scans using those three functions and compare them with the previous penalized likelihood scans. An application is presented using comprehensive state-wide data for Chagas' disease in puerperal women in Minas Gerais state, Brazil. CONCLUSIONS: We show that, compared to the other single-objective algorithms, multi-objective scans present better performance, regarding power, sensitivity and positive predicted value. The multi-objective non-connectivity scan is faster and better suited for the detection of moderately irregularly shaped clusters. The multi objective cohesion scan is most effective for the detection of highly irregularly shaped clusters. PMID- 21034452 TI - First trimester screening for trisomy 21 in gestational week 8-10 by ADAM12-S as a maternal serum marker. AB - BACKGROUND: A disintegrin and metalloprotease 12 (ADAM12-S) has previously been reported to be significantly reduced in maternal serum from women with fetal aneuploidy early in the first trimester and to significantly improve the quality of risk assessment for fetal trisomy 21 in prenatal screening. The aim of this study was to determine whether ADAM12-S is a useful serum marker for fetal trisomy 21 using the mixture model. METHOD: In this case control study ADAM12-S was measured by KRYPTOR ADAM12-S immunoassay in maternal serum from gestational weeks 8 to 11 in 46 samples of fetal trisomy 21 and in 645 controls. Comparison of sensitivity and specificity of first trimester screening for fetal trisomy 21 with or without ADAM12-S included in the risk assessment using the mixture model. RESULTS: The concentration of ADAM12-S increased from week 8 to 11 and was negatively correlated with maternal weight. Log MoM ADAM12-S was positively correlated with log MoM PAPP-A (r = 0.39, P < 0.001), and with log MoM free beta hCG (r = 0.21, P < 0.001). The median ADAM12-S MoM in cases of fetal trisomy 21 in gestational week 8 was 0.66 increasing to approx. 0.9 MoM in week 9 and 10. The use of ADAM12-S along with biochemical markers from the combined test (PAPP A, free beta hCG) with or without nuchal translucency measurement did not affect the detection rate or false positive rate of fetal aneuploidy as compared to routine screening using PAPP-A and free beta-hCG with or without nuchal translucency. CONCLUSION: The data show moderately decreased levels of ADAM12-S in cases of fetal aneuploidy in gestational weeks 8-11. However, including ADAM12 S in the routine risk does not improve the performance of first trimester screening for fetal trisomy 21. PMID- 21034453 TI - Prognostic value of lymph node metastases of differentiated thyroid cancer (DTC) according to the local advancement and range of surgical excision. AB - : In differentiated thyroid carcinoma (DTC) with primary tumor smaller than 1 cm, the routine central lymph node (LN) dissection is questioned, due to increased risk of post-surgery complications and lack of confirmed benefit. AIM: The analysis of prognostic significance of LN metastases, in DTC patients to verify the potential role of central neck lymphadenectomy on disease staging. MATERIALS AND METHODS: The group of 195 DTC patients, primarily operated between 2004 and 2005, was retrospectively analyzed. 184 patients after radical operation, with no distant metastases diagnosed before surgery, were included into analysis. LN metastases were observed in 55 of cases (28%). In 124 cases only dissection of central LN compartment was performed, in 36 patients also uni- or bilateral modified cervical lymphadectomy was carried out. In 24 patients with tumor limited to the thyroid gland without suspicious lymph nodes, the routine central lymph node dissection was not done. RESULTS: Median follow-up was 4 years. The 5 year overall and disease free survival standardized ratio were 100% and 95% respectively. The risk of LN metastases increased with the more locally advanced cancer. In the group of 124 patients, in whom only central LN dissection was performed, LN metastases were diagnosed in 15 cases (12%). No significant relation between multifocality and frequency of central and/or lateral LN metastases was noticed. Significant correlation between N feature and extrathyroidal invasion was observed (p = 0,0003). The presence of LN metastases was related to worsening of disease free survival from 99 to 90%. During the follow-up recurrence occurred in 6 (3%) cases. In 24 patients in whom only total thyroidectomy was done, no local or distant recurrence was observed. The assessment of early postoperative complications (hypoparathyroidism, paresis of vocal cords) indicated that the frequency of early calcium balance disturbances was significantly lower in patients in whom central LN dissection was not performed (p = 0,04) CONCLUSIONS: Our result indicate that in the early diagnosis of thyroid cancer, the occurrence of LN DTC metastases is rarer and was observed only in 12% of elective dissections of central LN node compartment, if no lateral dissection was indicated due to the lack of clinical suspicion. In DTC patients with tumor diameter <1 cm and no sonographical or inraoperative suspicion on LN involvement, routine central lymphadenectomy may be not obligatory. PMID- 21034454 TI - Enabling methods for community health mapping in developing countries. AB - BACKGROUND: Spatial epidemiology is useful but difficult to apply in developing countries due to the low availability of digitized maps and address systems, accurate population distributions, and computational tools. A community-based mapping approach was used to demonstrate that participatory geographic information system (PGIS) techniques can provide information helpful for health and community development. RESULTS: The PGIS process allowed for the rapid determination of sectional (neighborhood) boundaries within the city of Bo, Sierra Leone. When combined with data about hospital laboratory visits, a catchment area for one hospital in Bo could be established. A survey of households from within the catchment area determined that the average population per household (about 6 individuals) was similar to that found in the 2004 census. However, we also found that the average house was inhabited by more than one household, for an average of 17.5 inhabitants per residential building, which is critical information to know when estimating population size using remote imagery that can detect and enumerate buildings. CONCLUSIONS: The methods developed in this paper serve as a model for the involvement of communities in the generation of municipal maps and their application to community and health concerns. PMID- 21034455 TI - Plasma concentrations of osteopontin, but not thrombin-cleaved osteopontin, are associated with the presence and severity of nephropathy and coronary artery disease in patients with type 2 diabetes mellitus. AB - BACKGROUND: The aim of the present cross-sectional study was to assess possible associations between osteopontin (OPN), and thrombin-cleaved (N-half) OPN, and nephropathy and coronary artery disease (CAD) in patients with type 2 diabetes mellitus (T2DM). METHODS: Plasma levels of OPN, N-half OPN, and high-sensitivity C-reactive protein (hsCRP) were determined in 301 diabetic patients with (n = 226) or without (n = 75) angiographically documented CAD (luminal diameter narrowing >50%), as well as in 75 non-diabetic controls with normal angiography. The estimated glomerular filtration rate (eGFR) was calculated in all patients. RESULTS: Plasma levels of OPN and hsCRP were significantly higher in patients with T2DM compared with controls. In addition, there was a higher occurrence of moderate renal insufficiency and lower eGFR in patients with T2DM (all P < 0.01). T2DM patients in whom OPN levels were greater than the median value had higher serum creatinine levels, a greater prevalence of mild or moderate renal insufficiency, a higher incidence of CAD, and lower eGFR (all P < 0.05) than T2DM patients in whom OPN levels were the same as or lower than the median value. However, there were no differences in these parameters when patients were stratified according to plasma N-half OPN levels. Furthermore, there was a significant correlation between OPN, but not N-half OPN, and the severity of nephropathy and CAD in diabetes. After adjustment for potential confounders and treatments, multiple linear regression analysis demonstrated an independent association between OPN, but not N-half OPN, and eGFR. Multivariate logistic regression revealed that higher OPN levels conferred a fourfold greater risk of renal insufficiency and CAD in patients with T2DM. CONCLUSIONS: The results of the present study demonstrate that there is an independent association between plasma levels of OPN, but not N-half OPN, and the presence and severity of nephropathy and CAD in diabetes. PMID- 21034457 TI - Surgical management of life threatening events caused by intermittent aortic insufficiency in a native valve: case report. AB - We describe a case of a patient admitted with apparent life threatening events characterized by hypotension and bradycardia. The patient was ultimately found to have intermittent severe aortic insufficiency. Upon surgical exploration, abnormalities were discovered in the aortic valve, which had a small left coronary cusp with absence of the nodulus of Arantius. Following surgical repair of the valve, aimed at preventing the small cusp from becoming stuck in the open position, the patient has remained episode free for over one year. PMID- 21034456 TI - Reduction of radiation pneumonitis by V20-constraints in breast cancer. AB - INTRODUCTION: Adjuvant local-regional radiotherapy (LRRT) is routinely recommended for breast cancer patients. It is well known being related to pulmonary side-effects. We studied post-RT radiological changes on X-ray and CT, and correlated the findings with Quality of Life (QoL), common dosimetric factors and co-variates. The results were compared with a previously reported cohort of 137 irradiated women. METHODS: 88 women underwent chest X-ray and CT pre-and 4-5 months after 3-D planned LRRT, minimizing the dose to the ipsilateral lung to V20 < 30%. The lung field was divided into 3 regions and the development of post-RT density changes were graded (0-3). Patients with radiological changes were compared with non-responders. Clinical symptoms were registered and data on patient and treatment related co-variates were gathered prospectively. The ipsilateral lung dosimetric factors V13, V20, V30 and mean dose were calculated and QoL was assessed before and 4 months after RT. RESULTS: The use of dose volume constraints significally reduced moderate-severe radiological changes on chest X-ray compared with our earlier study (Chi square trend test: p < 0.001). Symptomatic pneumonitis was also rare in the present study. No agreement was found between CT and chest X-ray as diagnostic tools for post-RT pneumonitis. V13 correlated independently with radiological changes on CT (logistic regression: p = 0.04; ROC area: 0.7). The Co-variates smoking habits, age, chemotherapy, endocrine or trastuzumab therapy did not influence the outcome on multivariate analysis. QoL changes in physical function, i.e. fatigue, dyspnoea were not detected but there was a trend for a worse recovery after chemotherapy in patients with high V13 (Spearman Rank Correlation: p < 0.05). CONCLUSIONS: The use of dose-volume constraints significantly reduced post-RT radiological changes on chest X-ray in LRRT for BC. The lung changes on CT were also generally limited when we used this strategy and was not always picked up on chest X-ray. Variation in V13 alone was correlated with occurrence of lung changes on CT. PMID- 21034458 TI - Forecasting the need for medical specialists in Spain: application of a system dynamics model. AB - BACKGROUND: Spain has gone from a surplus to a shortage of medical doctors in very few years. Medium and long-term planning for health professionals has become a high priority for health authorities. METHODS: We created a supply and demand/need simulation model for 43 medical specialties using system dynamics. The model includes demographic, education and labour market variables. Several scenarios were defined. Variables controllable by health planners can be set as parameters to simulate different scenarios. The model calculates the supply and the deficit or surplus. Experts set the ratio of specialists needed per 1000 inhabitants with a Delphi method. RESULTS: In the scenario of the baseline model with moderate population growth, the deficit of medical specialists will grow from 2% at present (2800 specialists) to 14.3% in 2025 (almost 21 000). The specialties with the greatest medium-term shortages are Anesthesiology, Orthopedic and Traumatic Surgery, Pediatric Surgery, Plastic Aesthetic and Reparatory Surgery, Family and Community Medicine, Pediatrics, Radiology, and Urology. CONCLUSIONS: The model suggests the need to increase the number of students admitted to medical school. Training itineraries should be redesigned to facilitate mobility among specialties. In the meantime, the need to make more flexible the supply in the short term is being filled by the immigration of physicians from new members of the European Union and from Latin America. PMID- 21034460 TI - A multidisciplinary program of preparation for childbirth and motherhood: maternal anxiety and perinatal outcomes. AB - BACKGROUND: To study maternal anxiety and perinatal outcomes in pregnant women submitted to a Multidisciplinary Program for Childbirth and Motherhood Preparation (MPCM). METHODS: This is a not randomized controlled trial on 67 nulliparous pregnant women divided into two groups according to participation (MPCM Group; n = 38) or not (Control Group; n = 29) in MPCM. The program consisted of 10 meetings (between the 18th and the 38th gestational week) during which educational, physiotherapeutic and interaction activities were developed. Anxiety was quantified at the beginning and at the end of the gestational period by the Trace-State Anxiety Inventory (STAI). RESULTS: Initial maternal anxiety was equivalent between the groups. At the end of the gestational period, it was observed that anxiety levels increased in the Control Group and were maintained in the MPCM Group. A higher occurrence of vaginal deliveries (83.8%) and hospital discharge of three-day-older newborns (81.6%) as a result of MPCM was also significant. Levels of state-anxiety at the end of pregnancy showed a negative correlation with vaginal delivery, gestational age, birth weight and Apgar index at the first minute and positive correlation with the hospital period remaining of the newborns. CONCLUSION: In the study conditions, MPCM was associated with lower levels of maternal anxiety, a larger number of vaginal deliveries and shorter hospitalization time of newborns. It was not related to adverse perinatal outcomes. PMID- 21034459 TI - Induction of gastric cancer cell adhesion through transforming growth factor beta1-mediated peritoneal fibrosis. AB - BACKGROUND: Peritoneal dissemination is one of the main causes of death in gastric cancer patients. Transforming growth factor-beta1 (TGF-beta1), one of the most potent fibrotic stimuli for mesothelial cells, may play a key role in this processing. The purpose of this study is to elucidate the effects of TGF-beta1 on regulation of gastric cancer adhesion to mesothelial cells. METHODS: Peritoneal tissues and peritoneal wash fluid were obtained for hematoxylin and eosin staining or ELISA to measure fibrosis and TGF-beta1 levels, respectively. The peritoneal mesothelial cell line, HMrSV5, was used to determine the role of TGF beta1 in regulation of gastric cancer cell adhesion to mesothelial cells and expression of collagen, fibronectin, and Smad 2/3 by using adhesion assay, western blot, and RT-PCR. RESULTS: The data showed that TGF-beta1 treatment was able to induce collagen III and fibronectin expression in the mesothelial cells, which was associated with an increased adhesion ability of gastric cancer cells, but knockdown of minimal sites of cell binding domain of extracellular matrix can partially inhibit these effects. CONCLUSION: Peritoneal fibrosis induced by TGF beta1 may provide a favorable environment for the dissemination of gastric cancer. PMID- 21034461 TI - Incorporating significant amino acid pairs to identify O-linked glycosylation sites on transmembrane proteins and non-transmembrane proteins. AB - BACKGROUND: While occurring enzymatically in biological systems, O-linked glycosylation affects protein folding, localization and trafficking, protein solubility, antigenicity, biological activity, as well as cell-cell interactions on membrane proteins. Catalytic enzymes involve glycotransferases, sugar transferring enzymes and glycosidases which trim specific monosaccharides from precursors to form intermediate structures. Due to the difficulty of experimental identification, several works have used computational methods to identify glycosylation sites. RESULTS: By investigating glycosylated sites that contain various motifs between Transmembrane (TM) and non-Transmembrane (non-TM) proteins, this work presents a novel method, GlycoRBF, that implements radial basis function (RBF) networks with significant amino acid pairs (SAAPs) for identifying O-linked glycosylated serine and threonine on TM proteins and non-TM proteins. Additionally, a membrane topology is considered for reducing the false positives on glycosylated TM proteins. Based on an evaluation using five-fold cross-validation, the consideration of a membrane topology can reduce 31.4% of the false positives when identifying O-linked glycosylation sites on TM proteins. Via an independent test, GlycoRBF outperforms previous O-linked glycosylation site prediction schemes. CONCLUSION: A case study of Cyclic AMP-dependent transcription factor ATF-6 alpha was presented to demonstrate the effectiveness of GlycoRBF. Web-based GlycoRBF, which can be accessed at http://GlycoRBF.bioinfo.tw, can identify O-linked glycosylated serine and threonine effectively and efficiently. Moreover, the structural topology of Transmembrane (TM) proteins with glycosylation sites is provided to users. The stand-alone version of GlycoRBF is also available for high throughput data analysis. PMID- 21034462 TI - Coexpression of adrenomedullin and its receptor component proteins in the reproductive system of the rat during gestation. AB - BACKGROUND: Adrenomedullin (ADM), a novel vasorelaxant peptide, was found in human/rat ovaries and uteri. Plasma ADM level increases in pregnant women and pregnant rats. METHODS: The gene expression levels of Adm and its receptor components - Crlr, Ramp1, Ramp2 and Ramp3, the ADM peptide concentration and localization in the rat female reproductive system during gestation were studied by real-time RT-PCR, EIA and immunohistochemical techniques. RESULTS: The mRNAs of Adm and its receptor component and ADM were differentially distributed between implantation sites and inter-implantation sites of the pregnant uterus. The day on which vaginal sperm were found was taken to be pregnancy day 1. The Adm mRNA levels in the implantation sites of the uteri in mid- (day 12) and late pregnancy (day 17) were more than 10-fold higher than those in nonpregnancy, pre implantation (day 3) or early (day 7) pregnancy. ADM was localized in the endometrial stroma with increased immunoreactivity from nonpregnancy to pregnancy. The ADM level and the mRNA levels of Adm, Crlr, Ramp2 and Ramp3 in the corpus luteum all increased in late pregnancy compared with early pregnancy. The gene expression of Adm and it receptor components and intense immunostaining of ADM were also found in the oviduct during pregnancy. CONCLUSIONS: The gene expressions levels of Adm and its receptor components - Crlr, Ramp1, Ramp2 and Ramp3, and ADM peptide concentration exhibited a spatio-temporal pattern in the rat female reproductive system during gestation and this suggests that ADM may play important roles in gestation. PMID- 21034463 TI - Lymphocytopenia and neutrophil-lymphocyte count ratio predict bacteremia better than conventional infection markers in an emergency care unit. AB - INTRODUCTION: Absolute lymphocytopenia has been reported as a predictor of bacteremia in medical emergencies. Likewise, the neutrophil-lymphocyte count ratio (NLCR) has been shown a simple promising method to evaluate systemic inflammation in critically ill patients. METHODS: We retrospectively evaluated the ability of conventional infection markers, lymphocyte count and NLCR to predict bacteremia in adult patients admitted to the Emergency Department with suspected community-acquired bacteremia. The C-reactive protein (CRP) level, white blood cell (WBC) count, neutrophil count, lymphocyte count and NLCR were compared between patients with positive blood cultures (n = 92) and age-matched and gender-matched patients with negative blood cultures (n = 92) obtained upon Emergency Department admission. RESULTS: Significant differences between patients with positive and negative blood cultures were detected with respect to the CRP level (mean +/- standard deviation 176 +/- 138 mg/l vs. 116 +/- 103 mg/l; P = 0.042), lymphocyte count (0.8 +/- 0.5 * 109/l vs. 1.2 +/- 0.7 * 109/l; P < 0.0001) and NLCR (20.9 +/- 13.3 vs. 13.2 +/- 14.1; P < 0.0001) but not regarding WBC count and neutrophil count. Sensitivity, specificity, positive and negative predictive values were highest for the NLCR (77.2%, 63.0%, 67.6% and 73.4%, respectively). The area under the receiver operating characteristic curve was highest for the lymphocyte count (0.73; confidence interval: 0.66 to 0.80) and the NLCR (0.73; 0.66 to 0.81). CONCLUSIONS: In an emergency care setting, both lymphocytopenia and NLCR are better predictors of bacteremia than routine parameters like CRP level, WBC count and neutrophil count. Attention to these markers is easy to integrate in daily practice and without extra costs. PMID- 21034464 TI - On Hill et al's conjecture for calculating the subtree prune and regraft distance between phylogenies. AB - BACKGROUND: Recently, Hill et al. 1 implemented a new software package--called SPRIT--which aims at calculating the minimum number of horizontal gene transfer events that is needed to simultaneously explain the evolution of two rooted binary phylogenetic trees on the same set of taxa. To this end, SPRIT computes the closely related so-called rooted subtree prune and regraft distance between two phylogenies. However, calculating this distance is an NP-hard problem and exact algorithms are often only applicable to small- or medium-sized problem instances. Trying to overcome this problem, Hill et al. propose a divide-and conquer approach to speed up their algorithm and conjecture that this approach can be used to compute the rooted subtree prune and regraft distance exactly. RESULTS: In this note, we present a counterexample to Hill et al's conjecture and subsequently show that a modified version of their conjecture holds. CONCLUSION: While Hill et al's conjecture may result in an overestimate of the rooted subtree prune and regraft distance, a slightly more restricted version of their approach gives the desired outcome and can be applied to speed up the exact calculation of this distance between two phylogenies. PMID- 21034465 TI - Assessment of depression and anxiety in adult cancer outpatients: a cross sectional study. AB - BACKGROUND: The prevalence of anxiety and depressive disorders in cancer patients and its associated factors in Pakistan is not known. There is a need to develop an evidence base to help introduce interventions as untreated depression and anxiety can lead to significant morbidity. We assessed the prevalence of depression and anxiety among adult outpatients with and without cancer as well as the effect of various demographic, clinical and behavioral factors on levels of depression and anxiety in cancer patients. METHODS: This cross-sectional study was carried out in outpatient departments of Multan Institute of Nuclear Medicine and Radiotherapy and Nishtar Medical College Hospital, Multan. Aga Khan University Anxiety and Depression Scale (AKUADS) was used to define the presence of depression and anxiety in study participants. The sample consisted of 150 diagnosed cancer patients and 268 participants without cancer (control group). RESULTS: The mean age of cancer patients was 40.85 years (SD = 16.46) and median illness duration was 5.5 months, while the mean age of the control group was 39.58 years (SD = 11.74). Overall, 66.0% of the cancer patients were found to have depression and anxiety using a cutoff score of 20 on AKUADS. Among the control group, 109 subjects (40.7%) had depression and anxiety. Cancer patients were significantly more likely to suffer from distress compared to the control group (OR = 2.83, 95% CI = 1.89-4.25, P = 0.0001). Performing logistic regression analysis showed that age up to 40 years significantly influenced the prevalence of depression and anxiety in cancer patients. There was no statistically significant difference between gender, marital status, locality, education, income, occupation, physical activity, smoking, cancer site, illness duration and mode of treatment, surgery related to cancer and presence of depression and anxiety. Cancers highly associated with depression and anxiety were gastrointestinal malignancies, chest tumors and breast cancer. CONCLUSIONS: This study highlights high prevalence rates of depression and anxiety in cancer patients. Younger age was associated with a higher likelihood of meeting criteria for psychological morbidity. The findings support screening patients for symptoms of depression and anxiety as part of standard cancer care and referring those at a higher risk of developing psychological morbidity for appropriate care. PMID- 21034466 TI - CoNSEnsX: an ensemble view of protein structures and NMR-derived experimental data. AB - BACKGROUND: In conjunction with the recognition of the functional role of internal dynamics of proteins at various timescales, there is an emerging use of dynamic structural ensembles instead of individual conformers. These ensembles are usually substantially more diverse than conventional NMR ensembles and eliminate the expectation that a single conformer should fulfill all NMR parameters originating from 10(16) - 10(17) molecules in the sample tube. Thus, the accuracy of dynamic conformational ensembles should be evaluated differently to that of single conformers. RESULTS: We constructed the web application CoNSEnsX (Consistency of NMR-derived Structural Ensembles with eXperimental data) allowing fast, simple and convenient assessment of the correspondence of the ensemble as a whole with diverse independent NMR parameters available. We have chosen different ensembles of three proteins, human ubiquitin, a small protease inhibitor and a disordered subunit of cGMP phosphodiesterase 5/6 for detailed evaluation and demonstration of the capabilities of the CoNSEnsX approach. CONCLUSIONS: Our results present a new conceptual method for the evaluation of dynamic conformational ensembles resulting from NMR structure determination. The designed CoNSEnsX approach gives a complete evaluation of these ensembles and is freely available as a web service at http://consensx.chem.elte.hu. PMID- 21034467 TI - Decrypting the H-NS-dependent regulatory cascade of acid stress resistance in Escherichia coli. AB - BACKGROUND: H-NS regulates the acid stress resistance. The present study aimed to characterize the H-NS-dependent cascade governing the acid stress resistance pathways and to define the interplay between the different regulators. RESULTS: We combined mutational, phenotypic and gene expression analyses, to unravel the regulatory hierarchy in acid resistance involving H-NS, RcsB-P/GadE complex, HdfR, CadC, AdiY regulators, and DNA-binding assays to separate direct effects from indirect ones. RcsB-P/GadE regulatory complex, the general direct regulator of glutamate-, arginine- and lysine-dependent acid resistance pathways plays a central role in the regulatory cascade. However, H-NS also directly controls specific regulators of these pathways (e.g. cadC) and genes involved in general stress resistance (hdeAB, hdeD, dps, adiY). Finally, we found that in addition to H-NS and RcsB, a third regulator, HdfR, inversely controls glutamate-dependent acid resistance pathway and motility. CONCLUSIONS: H-NS lies near the top of the hierarchy orchestrating acid response centred on RcsB-P/GadE regulatory complex, the general direct regulator of glutamate-, arginine- and lysine-dependent acid resistance pathways. PMID- 21034468 TI - Cyanidin-3-glucoside inhibits ethanol-induced invasion of breast cancer cells overexpressing ErbB2. AB - BACKGROUND: Ethanol is a tumor promoter. Both epidemiological and experimental studies suggest that ethanol may enhance the metastasis of breast cancer cells. We have previously demonstrated that ethanol increased the migration/invasion of breast cancer cells expressing high levels of ErbB2. Amplification of ErbB2 is found in 20-30% of breast cancer patients and is associated with poor prognosis. We sought to identify agents that can prevent or ameliorate ethanol-induced invasion of breast cancer cells. Cyanidin-3-glucoside (C3G), an anthocyanin present in many vegetables and fruits, is a potent natural antioxidant. Ethanol exposure causes the accumulation of intracellular reactive oxygen species (ROS). This study evaluated the effect of C3G on ethanol-induced breast cancer cell migration/invasion. RESULTS: C3G attenuated ethanol-induced migration/invasion of breast cancer cells expressing high levels of ErbB2 (BT474, MDA-MB231 and MCF7(ErbB2)) in a concentration dependent manner. C3G decreased ethanol-mediated cell adhesion to the extracellular matrix (ECM) as well as the amount of focal adhesions and the formation of lamellipodial protrusion. It inhibited ethanol stimulated phosphorylation of ErbB2, cSrc, FAK and p130(Cas), as well as interactions among these proteins. C3G abolished ethanol-mediated p130(Cas)/JNK interaction. CONCLUSIONS: C3G blocks ethanol-induced activation of the ErbB2/cSrc/FAK pathway which is necessary for cell migration/invasion. C3G may be beneficial in preventing/reducing ethanol-induced breast cancer metastasis. PMID- 21034469 TI - Systemic treatment with liver X receptor agonists raises apolipoprotein E, cholesterol, and amyloid-beta peptides in the cerebral spinal fluid of rats. AB - BACKGROUND: Apolipoprotein E (apoE) is a major cholesterol transport protein found in association with brain amyloid from Alzheimer's disease (AD) patients and the epsilon4 allele of apoE is a genetic risk factor for AD. Previous studies have shown that apoE forms a stable complex with amyloid beta (Abeta) peptides in vitro and that the state of apoE lipidation influences the fate of brain Abeta, i.e., lipid poor apoE promotes Abeta aggregation/deposition while fully lipidated apoE favors Abeta degradation/clearance. In the brain, apoE levels and apoE lipidation are regulated by the liver X receptors (LXRs). RESULTS: We investigated the hypothesis that increased apoE levels and lipidation induced by LXR agonists facilitates Abeta efflux from the brain to the cerebral spinal fluid (CSF). We also examined if the brain expression of major apoE receptors potentially involved in apoE-mediated Abeta clearance was altered by LXR agonists. ApoE, cholesterol, Abeta40, and Abeta42 levels were all significantly elevated in the CSF of rats after only 3 days of treatment with LXR agonists. A significant reduction in soluble brain Abeta40 levels was also detected after 6 days of LXR agonist treatment. CONCLUSIONS: Our novel findings suggest that central Abeta lowering caused by LXR agonists appears to involve an apoE/cholesterol-mediated transport of Abeta to the CSF and that differences between the apoE isoforms in mediating this clearance pathway may explain why individuals carrying one or two copies of APOE epsilon4 have increased risk for AD. PMID- 21034470 TI - A novel mutation in the calcium-sensing receptor gene in an Irish pedigree showing familial hypocalciuric hypercalcemia: a case report. AB - INTRODUCTION: Familial hypocalciuric hypercalcemia is a rare autosomal dominant disorder characterized by asymptomatic and non-progressive hypercalcemia due to mutations of the calcium-sensing receptor gene. Disorders of calcium metabolism are very common in the elderly, and they can coexist with familial hypocalciuric hypercalcemia in affected families. CASE PRESENTATION: We describe an Irish family with hypercalcemia and hypocalciuria. The proband, an 80-year-old Irish woman, presented with hypercalcemia, relative hypocalciuria, and an elevated parathormone level. She also had chronic kidney disease stage 3 and vitamin D deficiency. Two of her sons were also found to be hypercalcemic and hypocalciuric. DNA sequencing identified a novel missense inactivating mutation in the calcium sensing-receptor gene of the proband and her two hypercalcemic sons. CONCLUSION: Familial hypocalciuric hypercalcemia due to a novel mutation in the calcium-sensing receptor gene was diagnosed in the proband and her two sons. Disorders of calcium metabolism can be multifarious in the elderly. We suggest that testing first degree relatives for calcium levels and DNA sequencing may have a role in the assessment of elderly patients with parathormone-related hypercalcemia. PMID- 21034471 TI - Visual loss secondary to eosinophilic mucin rhinosinusitis in a woman: a case report. AB - INTRODUCTION: Eosinophilic mucin rhinosinusitis is an inflammatory pathological condition of the nose and paranasal sinuses. It is rare, occurs in immunocompetent patients and is characterised by peripheral eosinophilia and extensive bilateral sinus disease. To the best of our knowledge, visual loss with this condition has not been previously reported. CASE PRESENTATION: We present the case of a 26-year-old Asian woman with a background history of chronic sinusitis who presented with acute left-sided visual loss. Imaging showed significant opacification in the frontal, ethmoidal and sphenoidal sinuses as well as evidence of a unilateral optic neuritis. Histological analysis of sinus mucin revealed dense eosinophilic infiltrate and, despite medical and surgical intervention, vision was not restored in her left eye. CONCLUSION: We introduce visual loss as a complication of eosinophilic mucin rhinosinusitis. This adds further evidence to previous reports in the literature that optic neuropathy in sinusitis can occur secondary to non-compressive mechanisms. We also describe a rare finding: the vision in this patient did not improve following steroid therapy, antifungal therapy or surgical intervention. There are very few such cases described in the literature. We conclude that chronic sinusitis is an indolent inflammatory process which can cause visual loss and we reiterate the importance of recognizing and considering sinusitis as a cause of visual loss in patients in order that prompt medical and surgical treatment of the underlying disease can be initiated. PMID- 21034472 TI - Genotator: a disease-agnostic tool for genetic annotation of disease. AB - BACKGROUND: Disease-specific genetic information has been increasing at rapid rates as a consequence of recent improvements and massive cost reductions in sequencing technologies. Numerous systems designed to capture and organize this mounting sea of genetic data have emerged, but these resources differ dramatically in their disease coverage and genetic depth. With few exceptions, researchers must manually search a variety of sites to assemble a complete set of genetic evidence for a particular disease of interest, a process that is both time-consuming and error-prone. METHODS: We designed a real-time aggregation tool that provides both comprehensive coverage and reliable gene-to-disease rankings for any disease. Our tool, called Genotator, automatically integrates data from 11 externally accessible clinical genetics resources and uses these data in a straightforward formula to rank genes in order of disease relevance. We tested the accuracy of coverage of Genotator in three separate diseases for which there exist specialty curated databases, Autism Spectrum Disorder, Parkinson's Disease, and Alzheimer Disease. Genotator is freely available at http://genotator.hms.harvard.edu. RESULTS: Genotator demonstrated that most of the 11 selected databases contain unique information about the genetic composition of disease, with 2514 genes found in only one of the 11 databases. These findings confirm that the integration of these databases provides a more complete picture than would be possible from any one database alone. Genotator successfully identified at least 75% of the top ranked genes for all three of our use cases, including a 90% concordance with the top 40 ranked candidates for Alzheimer Disease. CONCLUSIONS: As a meta-query engine, Genotator provides high coverage of both historical genetic research as well as recent advances in the genetic understanding of specific diseases. As such, Genotator provides a real time aggregation of ranked data that remains current with the pace of research in the disease fields. Genotator's algorithm appropriately transforms query terms to match the input requirements of each targeted databases and accurately resolves named synonyms to ensure full coverage of the genetic results with official nomenclature. Genotator generates an excel-style output that is consistent across disease queries and readily importable to other applications. PMID- 21034473 TI - Control of neglected tropical diseases needs a long-term commitment. AB - BACKGROUND: Neglected tropical diseases are widespread, particularly in sub Saharan Africa, affecting over 2 billion individuals. Control of these diseases has gathered pace in recent years, with increased levels of funding from a number of governmental or non-governmental donors. Focus has currently been on five major 'tool-ready' neglected tropical diseases (lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminthiasis and trachoma), using a package of integrated drug delivery according to the World Health Organization guidelines for preventive chemotherapy. DISCUSSION: Success in controlling these neglected tropical diseases has been achieved in a number of countries in recent history. Experience from these successes suggests that long term sustainable control of these diseases requires: (1) a long-term commitment from a wider range of donors and from governments of endemic countries; (2) close partnerships of donors, World Health Organization, pharmaceutical industries, governments of endemic countries, communities, and non-governmental developmental organisations; (3) concerted action from more donor countries to provide the necessary funds, and from the endemic countries to work together to prevent cross border disease transmission; (4) comprehensive control measures for certain diseases; and (5) strengthened primary healthcare systems as platforms for the national control programmes and capacity building through implementation of the programmes. CONCLUSIONS: The current level of funding for the control of neglected tropical diseases has never been seen before, but it is still not enough to scale up to the 2 billion people in all endemic countries. While more donors are sought, the stakeholders must work in a coordinated and harmonised way to identify the priority areas and the best delivery approaches to use the current funds to the maximum effect. Case management and other necessary control measures should be supported through the current major funding streams in order to achieve the objectives of the control of these diseases. For a long-term and sustainable effort, control of neglected tropical diseases should also be integrated into national primary healthcare systems. PMID- 21034474 TI - Structure and dynamics of the pan-genome of Streptococcus pneumoniae and closely related species. AB - BACKGROUND: Streptococcus pneumoniae is one of the most important causes of microbial diseases in humans. The genomes of 44 diverse strains of S. pneumoniae were analyzed and compared with strains of non-pathogenic streptococci of the Mitis group. RESULTS: Despite evidence of extensive recombination, the S. pneumoniae phylogenetic tree revealed six major lineages. With the exception of serotype 1, the tree correlated poorly with capsular serotype, geographical site of isolation and disease outcome. The distribution of dispensable genes--genes present in more than one strain but not in all strains--was consistent with phylogeny, although horizontal gene transfer events attenuated this correlation in the case of ancient lineages. Homologous recombination, involving short stretches of DNA, was the dominant evolutionary process of the core genome of S. pneumoniae. Genetic exchange occurred both within and across the borders of the species, and S. mitis was the main reservoir of genetic diversity of S. pneumoniae. The pan-genome size of S. pneumoniae increased logarithmically with the number of strains and linearly with the number of polymorphic sites of the sampled genomes, suggesting that acquired genes accumulate proportionately to the age of clones. Most genes associated with pathogenicity were shared by all S. pneumoniae strains, but were also present in S. mitis, S. oralis and S. infantis, indicating that these genes are not sufficient to determine virulence. CONCLUSIONS: Genetic exchange with related species sharing the same ecological niche is the main mechanism of evolution of S. pneumoniae. The open pan-genome guarantees the species a quick and economical response to diverse environments. PMID- 21034475 TI - Primary gastric adenosquamous carcinoma in a Caucasian woman: a case report. AB - INTRODUCTION: Most gastric tumors are adenocarcinomas. Primary gastric adenosquamous carcinoma is a rare malignancy, mostly associated with Asian populations. It constitutes less than one percent of all gastric carcinomas and its clinical presentation is the same as adenocarcinoma. It occurs more frequently in the proximal stomach, usually presents with muscular layer invasion and tends to be found in advanced stages at diagnosis, with a worse prognosis than adenocarcinoma. CASE PRESENTATION: We report the case of an 84-year-old Caucasian woman with an adenosquamous carcinoma extending to her serosa with lymphatic and venous invasion (T3N1M1). Nodal and hepatic metastasis presented with both cellular types, with dominance of the squamous component. CONCLUSIONS: Adenosquamous gastric cancer is a rare diagnosis in western populations. We present the case of a woman with a very aggressive adenosquamous carcinoma with a preponderance of squamous cell component in the metastasis. Several origins have been proposed for this kind of carcinoma; either evolution from adenocarcinoma de differentiation or stem cell origin might be possible. The hypothesis that a particular histological type of gastric cancer may arise from stem cells might be a field of research in oncological disease of the stomach. PMID- 21034477 TI - Rapid haplotype inference for nuclear families. AB - Hapi is a new dynamic programming algorithm that ignores uninformative states and state transitions in order to efficiently compute minimum-recombinant and maximum likelihood haplotypes. When applied to a dataset containing 103 families, Hapi performs 3.8 and 320 times faster than state-of-the-art algorithms. Because Hapi infers both minimum-recombinant and maximum likelihood haplotypes and applies to related individuals, the haplotypes it infers are highly accurate over extended genomic distances. PMID- 21034476 TI - Central venous O2 saturation and venous-to-arterial CO2 difference as complementary tools for goal-directed therapy during high-risk surgery. AB - INTRODUCTION: Central venous oxygen saturation (ScvO2) is a useful therapeutic target in septic shock and high-risk surgery. We tested the hypothesis that central venous-to-arterial carbon dioxide difference (P(cv-a)CO2), a global index of tissue perfusion, could be used as a complementary tool to ScvO2 for goal directed fluid therapy (GDT) to identify persistent low flow after optimization of preload has been achieved by fluid loading during high-risk surgery. METHODS: This is a secondary analysis of results obtained in a study involving 70 adult patients (ASA I to III), undergoing major abdominal surgery, and treated with an individualized goal-directed fluid replacement therapy. All patients were managed to maintain a respiratory variation in peak aortic flow velocity below 13%. Cardiac index (CI), oxygen delivery index (DO2i), ScvO2, P(cv-a)CO2 and postoperative complications were recorded blindly for all patients. RESULTS: A total of 34% of patients developed postoperative complications. At baseline, there was no difference in demographic or haemodynamic variables between patients who developed complications and those who did not. In patients with complications, during surgery, both mean ScvO2 (78 +/- 4 versus 81 +/- 4%, P = 0.017) and minimal ScvO2 (minScvO2) (67 +/- 6 versus 72 +/- 6%, P = 0.0017) were lower than in patients without complications, despite perfusion of similar volumes of fluids and comparable CI and DO2i values. The optimal ScvO2 cut-off value was 70.6% and minScvO2 < 70% was independently associated with the development of postoperative complications (OR = 4.2 (95% CI: 1.1 to 14.4), P = 0.025). P(cv-a)CO2 was larger in patients with complications (7.8 +/- 2 versus 5.6 +/- 2 mmHg, P < 10-6). In patients with complications and ScvO2 >= 71%, P(cv a)CO2 was also significantly larger (7.7 +/- 2 versus 5.5 +/- 2 mmHg, P < 10-6) than in patients without complications. The area under the receiver operating characteristic (ROC) curve was 0.785 (95% CI: 0.74 to 0.83) for discrimination of patients with ScvO2 >= 71% who did and did not develop complications, with 5 mmHg as the most predictive threshold value. CONCLUSIONS: ScvO2 reflects important changes in O2 delivery in relation to O2 needs during the perioperative period. A P(cv-a)CO2 < 5 mmHg might serve as a complementary target to ScvO2 during GDT to identify persistent inadequacy of the circulatory response in face of metabolic requirements when an ScvO2 >= 71% is achieved. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT00852449. PMID- 21034479 TI - A randomised clinical trial on a comprehensive geriatric assessment and intensive home follow-up after hospital discharge: the Transitional Care Bridge. AB - BACKGROUND: Older patients are at high risk for poor outcomes after acute hospital admission. The mortality rate in these patients is approximately 20%, whereas 30% of the survivors decline in their level of activities of daily living (ADL) functioning three months after hospital discharge. Most diseases and geriatric conditions that contribute to poor outcomes could be subject to pro active intervention; not only during hospitalization, but also after discharge. This paper presents the design of a randomised controlled clinical trial concerning the effect of a pro-active, multi-component, nurse-led transitional care program following patients for six months after hospital admission. METHODS/DESIGN: Three hospitals in the Netherlands will participate in the multi centre, double-blind, randomised clinical trial comparing a pro-active multi component nurse-led transitional care program to usual care after discharge. All patients acutely admitted to the Department of Internal Medicine who are 65 years and older, hospitalised for at least 48 hours and are at risk for functional decline are invited to participate in the study. All patients will receive integrated geriatric care by a geriatric consultation team during hospital admission. Randomization, which will be stratified by study site and cognitive impairment, will be conducted during admission. The intervention group will receive the transitional care bridge program, consisting of a handover moment with a community care Care Nurse (CN) during hospital admission and five home visits after discharge. The control group will receive 'care as usual' after discharge. The main outcome is the level of ADL functioning six months after discharge compared to premorbid functioning measured with the Katz ADL index. Secondary outcomes include; survival, cognitive functioning, quality of life, and health care utilization, satisfaction of the patient and primary care giver with the transitional care bridge program. All outcomes will be measured at three, six and twelve months after discharge. Approximately 674 patients will be enrolled to either the intervention or control group. DISCUSSION: The study will provide new knowledge on a combined intervention of integrated care during hospital admission, a proactive handover moment before discharge and intensive home visits after discharge. TRIAL REGISTRATION: TRIAL REGISTRATION NUMBER: NTR 2384. PMID- 21034480 TI - Predicting domain-domain interaction based on domain profiles with feature selection and support vector machines. AB - BACKGROUND: Protein-protein interaction (PPI) plays essential roles in cellular functions. The cost, time and other limitations associated with the current experimental methods have motivated the development of computational methods for predicting PPIs. As protein interactions generally occur via domains instead of the whole molecules, predicting domain-domain interaction (DDI) is an important step toward PPI prediction. Computational methods developed so far have utilized information from various sources at different levels, from primary sequences, to molecular structures, to evolutionary profiles. RESULTS: In this paper, we propose a computational method to predict DDI using support vector machines (SVMs), based on domains represented as interaction profile hidden Markov models (ipHMM) where interacting residues in domains are explicitly modeled according to the three dimensional structural information available at the Protein Data Bank (PDB). Features about the domains are extracted first as the Fisher scores derived from the ipHMM and then selected using singular value decomposition (SVD). Domain pairs are represented by concatenating their selected feature vectors, and classified by a support vector machine trained on these feature vectors. The method is tested by leave-one-out cross validation experiments with a set of interacting protein pairs adopted from the 3DID database. The prediction accuracy has shown significant improvement as compared to InterPreTS (Interaction Prediction through Tertiary Structure), an existing method for PPI prediction that also uses the sequences and complexes of known 3D structure. CONCLUSIONS: We show that domain-domain interaction prediction can be significantly enhanced by exploiting information inherent in the domain profiles via feature selection based on Fisher scores, singular value decomposition and supervised learning based on support vector machines. Datasets and source code are freely available on the web at http://liao.cis.udel.edu/pub/svdsvm. Implemented in Matlab and supported on Linux and MS Windows. PMID- 21034478 TI - Ethnopharmacological survey among migrants living in the Southeast Atlantic Forest of Diadema, Sao Paulo, Brazil. AB - BACKGROUND: Understanding how people of diverse cultural backgrounds have traditionally used plants and animals as medicinal substances during displacements is one of the most important objectives of ethnopharmacological studies. An ethnopharmacological survey conducted among migrants living in the Southeast Atlantic Forest remnants (Diadema, Sao Paulo, Brazil) is presented herein. METHODS: Ethnographical methods were used to select and interview the migrants, and botanical and zoological techniques were employed to collect the indicated resources. RESULTS: We interviewed five migrants who described knowledge on 12 animals and 85 plants. Only 78 plants were present in Diadema, they belong to 37 taxonomic families; 68 were used exclusively for medicinal purposes, whereas 10 were reported to be toxic and/or presented some restriction of use. These taxa were grouped into 12 therapeutic categories (e.g., gastrointestinal disturbances, inflammatory processes or respiratory problems) based on the 41 individual complaints cited by the migrants. While the twelve animal species were used by the migrants to treat nine complaints; these were divided into six categories, the largest of which related to respiratory problems. None of the animal species and only 57 of the 78 plant species analysed in the present study were previously reported in the pharmacological literature; the popular knowledge concurred with academic findings for 30 of the plants. The seven plants [Impatiens hawkeri W. Bull., Artemisia canphorata Vill., Equisetum arvensis L., Senna pendula (Humb. & Bonpl. ex Willd.) H.S. Irwin & Barneby, Zea mays L., Fevillea passiflora Vell. and Croton fuscescens Spreng)] and the two animals (Atta sexdens and Periplaneta americana) that showed maintenance of use among migrants during their displacement in Brazilian territory, have not been studied by pharmacologists yet. CONCLUSIONS: Thus, they should be highlighted and focused in further pharmacology and phytochemical studies, since the persistence of their uses can be indicative of bioactive potentials. PMID- 21034481 TI - Barriers of access to care in a managed competition model: lessons from Colombia. AB - BACKGROUND: The health sector reform in Colombia, initiated by Law 100 (1993) that introduced a managed competition model, is generally presented as a successful experience of improving access to care through a health insurance regulated market. The study's objective is to improve our understanding of the factors influencing access to the continuum of care in the Colombian managed competition model, from the social actors' point of view. METHODS: An exploratory, descriptive-interpretative qualitative study was carried out, based on case studies of four healthcare networks in rural and urban areas. Individual semi-structured interviews were conducted to a three stage theoretical sample: I) cases, II) providers and III) informants: insured and uninsured users (35), health professionals (51), administrative personnel (20), and providers' (18) and insurers' (10) managers. Narrative content analysis was conducted; segmented by cases, informant's groups and themes. RESULTS: Access, particularly to secondary care, is perceived as complex due to four groups of obstacles with synergetic effects: segmented insurance design with insufficient services covered; insurers' managed care and purchasing mechanisms; providers' networks structural and organizational limitations; and, poor living conditions. Insurers' and providers' values based on economic profit permeate all factors. Variations became apparent between the two geographical areas and insurance schemes. In the urban areas barriers related to market functioning predominate, whereas in the rural areas structural deficiencies in health services are linked to insufficient public funding. While financial obstacles are dominant in the subsidized regime, in the contributory scheme supply shortage prevails, related to insufficient private investment. CONCLUSIONS: The results show how in the Colombian healthcare system structural and organizational barriers to care access, that are common in developing countries, are widened by both the insurers' use of mechanisms that limit the utilization and the public healthcare providers' change of behavior in a competition environment. They provide evidence to question the promotion of the managed competition model in low and middle-income countries. PMID- 21034482 TI - Diagnostic potential of plasma carboxymethyllysine and carboxyethyllysine in multiple sclerosis. AB - BACKGROUND: This study compared the level of advanced glycation end products (AGEs), N-(Carboxymethyl)lysine (CML) and N-(Carboxyethyl)lysine (CEL), in patients with multiple sclerosis (MS) and healthy controls (HCs), correlating these markers with clinical indicators of MS disease severity. METHODS: CML and CEL plasma levels were analyzed in 99 MS patients and 43 HCs by tandem mass spectrometry (LC/MS/MS). Patients were stratified based on drug modifying therapies (DMTs) including interferon beta, glatiramer acetate and natalizumab. RESULTS: The level of plasma CEL, but not CML, was significantly higher in DMT naive MS patients when compared to HCs (P < 0.001). Among MS patients, 91% had higher than mean plasma CEL observed in HCs. DMTs reduced CML and CEL plasma levels by approximately 13% and 40% respectively. CML and CEL plasma levels correlated with the rate of MS clinical relapse. CONCLUSION: Our results suggest that AGEs in general and CEL in particular could be useful biomarkers in MS clinical practice. Longitudinal studies are warranted to determine any causal relationship between changes in plasma level of AGEs and MS disease pathology. These studies will pave the way for use of AGE inhibitors and AGE-breaking agents as new therapeutic modalities in MS. PMID- 21034483 TI - Integrative care for the management of low back pain: use of a clinical care pathway. AB - BACKGROUND: For the treatment of chronic back pain, it has been theorized that integrative care plans can lead to better outcomes than those achieved by monodisciplinary care alone, especially when using a collaborative, interdisciplinary, and non-hierarchical team approach. This paper describes the use of a care pathway designed to guide treatment by an integrative group of providers within a randomized controlled trial. METHODS: A clinical care pathway was used by a multidisciplinary group of providers, which included acupuncturists, chiropractors, cognitive behavioral therapists, exercise therapists, massage therapists and primary care physicians. Treatment recommendations were based on an evidence-informed practice model, and reached by group consensus. Research study participants were empowered to select one of the treatment recommendations proposed by the integrative group. Common principles and benchmarks were established to guide treatment management throughout the study. RESULTS: Thirteen providers representing 5 healthcare professions collaborated to provide integrative care to study participants. On average, 3 to 4 treatment plans, each consisting of 2 to 3 modalities, were recommended to study participants. Exercise, massage, and acupuncture were both most commonly recommended by the team and selected by study participants. Changes to care commonly incorporated cognitive behavioral therapy into treatment plans. CONCLUSION: This clinical care pathway was a useful tool for the consistent application of evidence-based care for low back pain in the context of an integrative setting. TRIAL REGISTRATION: ClinicalTrials.gov NCT00567333. PMID- 21034484 TI - Effect of histamine-2-receptor antagonists versus sucralfate on stress ulcer prophylaxis in mechanically ventilated patients: a meta-analysis of 10 randomized controlled trials. AB - INTRODUCTION: We conducted a meta-analysis in order to investigate the effect of histamine-2-receptor antagonists (H2RA) versus sucralfate on stress ulcer prophylaxis in mechanically ventilated patients in the intensive care unit (ICU). METHODS: A systematic literature search of Medline, EMBASE, Cochrane Central Register of Controlled Trials (1966 to January 2010) was conducted using specific search terms. A review of Web of Science and a manual review of references were also performed. Eligible studies were randomized control trials (RCTs) that compared H2RA and sucralfate for the prevention of stress ulcer in mechanically ventilated patients. Main outcome measures were rates of overt bleeding, clinically important gastrointestinal (GI) bleeding, ventilator-associated pneumonia, gastric colonization and ICU mortality. RESULTS: Ten RCTs with 2,092 participants on mechanical ventilation were identified. Meta-analysis showed there was a trend toward decreased overt bleeding when H2RA was compared with sucralfate (OR = 0.87, 95% CI: 0.49 to 1.53). A total of 12 clinically important GI bleeding events occurred among 667 patients (1.8%) in the H2RA group compared with 26 events among 673 patients (3.9%) in the sucralfate groups. Prophylaxis with sucralfate decreased the incidence of gastric colonization (OR = 2.03, 95% CI: 1.29 to 3.19) and ventilator-associated pneumonia (OR = 1.32, 95% CI: 1.07 to 1.64). Subgroup analysis showed H2RA was not superior to sucralfate in reducing early-onset pneumonia (OR = 0.62, 95%CI: 0.36 to 1.07) but had a higher late onset pneumonia rate (OR = 4.36, 95%CI: 2.09 to 9.09) relative to sucralfate. No statistically significant reduction was observed in mortality of ICU between groups (OR = 1.08, 95% CI: 0.86 to 1.34). CONCLUSIONS: In patients with mechanical ventilation, H2RA resulted in no differential effectiveness in treating overt bleeding, but had higher rates of gastric colonization and ventilator-associated pneumonia. Additional RCTs of stress ulcer prophylaxis with H2RA and sucralfate are needed to establish the net benefit and risks of adverse effect in mechanically ventilated patients. PMID- 21034485 TI - Inhibitors of inflammation and endogenous surfactant pool size as modulators of lung injury with initiation of ventilation in preterm sheep. AB - BACKGROUND: Increased pro-inflammatory cytokines in tracheal aspirates correlate with the development of BPD in preterm infants. Ventilation of preterm lambs increases pro-inflammatory cytokines and causes lung inflammation. OBJECTIVE: We tested the hypothesis that selective inhibitors of pro-inflammatory signaling would decrease lung inflammation induced by ventilation in preterm newborn lambs. We also examined if the variability in injury response was explained by variations in the endogenous surfactant pool size. METHODS: Date-mated preterm lambs (n = 28) were operatively delivered and mechanically ventilated to cause lung injury (tidal volume escalation to 15 mL/kg by 15 min at age). The lambs then were ventilated with 8 mL/kg tidal volume for 1 h 45 min. Groups of animals randomly received specific inhibitors for IL-8, IL-1, or NF-kappaB. Unventilated lambs (n = 7) were the controls. Bronchoalveolar lavage fluid (BALF) and lung samples were used to quantify inflammation. Saturated phosphatidylcholine (Sat PC) was measured in BALF fluid and the data were stratified based on a level of 5 MUmol/kg (~8 mg/kg surfactant). RESULTS: The inhibitors did not decrease the cytokine levels or inflammatory response. The inflammation increased as Sat PC pool size in BALF decreased. Ventilated lambs with a Sat PC level > 5 MUmol/kg had significantly decreased markers of injury and lung inflammation compared with those lambs with < 5 MUmol/kg. CONCLUSION: Lung injury caused by high tidal volumes at birth were decreased when endogenous surfactant pool sizes were larger. Attempts to decrease inflammation by blocking IL-8, IL-1 or NF-kappaB were unsuccessful. PMID- 21034487 TI - Manufacture of IRDye800CW-coupled Fe3O4 nanoparticles and their applications in cell labeling and in vivo imaging. AB - BACKGROUND: In recent years, near-infrared fluorescence (NIRF)-labeled iron nanoparticles have been synthesized and applied in a number of applications, including the labeling of human cells for monitoring the engraftment process, imaging tumors, sensoring the in vivo molecular environment surrounding nanoparticles and tracing their in vivo biodistribution. These studies demonstrate that NIRF-labeled iron nanoparticles provide an efficient probe for cell labeling. Furthermore, the in vivo imaging studies show excellent performance of the NIR fluorophores. However, there is a limited selection of NIRF-labeled iron nanoparticles with an optimal wavelength for imaging around 800 nm, where tissue autofluorescence is minimal. Therefore, it is necessary to develop additional alternative NIRF-labeled iron nanoparticles for application in this area. RESULTS: This study manufactured 12-nm DMSA-coated Fe3O4 nanoparticles labeled with a near-infrared fluorophore, IRDye800CW (excitation/emission, 774/789 nm), to investigate their applicability in cell labeling and in vivo imaging. The mouse macrophage RAW264.7 was labeled with IRDye800CW-labeled Fe3O4 nanoparticles at concentrations of 20, 30, 40, 50, 60, 80 and 100 MUg/ml for 24 h. The results revealed that the cells were efficiently labeled by the nanoparticles, without any significant effect on cell viability. The nanoparticles were injected into the mouse via the tail vein, at dosages of 2 or 5 mg/kg body weight, and the mouse was discontinuously imaged for 24 h. The results demonstrated that the nanoparticles gradually accumulated in liver and kidney regions following injection, reaching maximum concentrations at 6 h post injection, following which they were gradually removed from these regions. After tracing the nanoparticles throughout the body it was revealed that they mainly distributed in three organs, the liver, spleen and kidney. Real-time live-body imaging effectively reported the dynamic process of the biodistribution and clearance of the nanoparticles in vivo. CONCLUSION: IRDye800CW-labeled Fe3O4 nanoparticles provide an effective probe for cell-labeling and in vivo imaging. PMID- 21034486 TI - Eight week exposure to a high sugar high fat diet results in adiposity gain and alterations in metabolic biomarkers in baboons (Papio hamadryas sp.). AB - BACKGROUND: Baboons (Papio hamadryas Sp.) develop features of the cardiometabolic syndrome and represent a clinically-relevant animal model in which to study the aetiology of the disorder. To further evaluate the baboon as a model for the study of the cardiometabolic syndrome, we developed a high sugar high fat diet and hypothesized that it could be used to induce adiposity gain and affect associated circulating biomarkers. METHODS: We developed a diet enriched with monosaccharides and saturated fatty acids that was composed of solid and liquid energy sources. We provided a group of baboons (n = 9) ad libitum access to this diet for 8 weeks. Concurrently, a control group (n = 6) was maintained with ad libitum access to a low sugar low fat baseline diet and normal water for 8 weeks. Body composition was determined by dual-energy X-ray absorptiometry and circulating metabolic biomarkers were measured using standard methodology before and after the 8 week study period. RESULTS: Neither body composition nor circulating biomarkers changed in the control group. Following the 8 weeks, the intervention group had a significant increase in fat mass (1.71 +/- 0.98 vs. 3.23 +/- 1.70 kg, p = 0.004), triglyceride (55 +/- 13 vs. 109 +/- 67 mg/dL, p = 0.006,), and leptin (1.19 +/- 1.40 vs. 3.29 +/- 2.32 ng/mL, p = 0.001) and a decline in adiponectin concentrations (33530 +/- 9744 vs. 23330 +/- 7863 ng/mL, p = 0.002). Percentage haemoglobin A1C (4.0 +/- 0.3 vs. 6.0 +/- 1.4, p = 0.002) also increased in the intervention group. CONCLUSIONS: Our findings indicate that when exposed to a high sugar high fat diet, young adult male baboons develop increased body fat and triglyceride concentrations, altered adipokine concentrations, and evidence of altered glucose metabolism. Our findings are in keeping with observations in humans and further demonstrate the potential utility of this highly clinically-relevant animal model for studying diet-induced metabolic dysregulation. PMID- 21034488 TI - Structural modelling and comparative analysis of homologous, analogous and specific proteins from Trypanosoma cruzi versus Homo sapiens: putative drug targets for chagas' disease treatment. AB - BACKGROUND: Trypanosoma cruzi is the etiological agent of Chagas' disease, an endemic infection that causes thousands of deaths every year in Latin America. Therapeutic options remain inefficient, demanding the search for new drugs and/or new molecular targets. Such efforts can focus on proteins that are specific to the parasite, but analogous enzymes and enzymes with a three-dimensional (3D) structure sufficiently different from the corresponding host proteins may represent equally interesting targets. In order to find these targets we used the workflows MHOLline and AnEnPi obtaining 3D models from homologous, analogous and specific proteins of Trypanosoma cruzi versus Homo sapiens. RESULTS: We applied genome wide comparative modelling techniques to obtain 3D models for 3,286 predicted proteins of T. cruzi. In combination with comparative genome analysis to Homo sapiens, we were able to identify a subset of 397 enzyme sequences, of which 356 are homologous, 3 analogous and 38 specific to the parasite. CONCLUSIONS: In this work, we present a set of 397 enzyme models of T. cruzi that can constitute potential structure-based drug targets to be investigated for the development of new strategies to fight Chagas' disease. The strategies presented here support the concept of structural analysis in conjunction with protein functional analysis as an interesting computational methodology to detect potential targets for structure-based rational drug design. For example, 2,4 dienoyl-CoA reductase (EC 1.3.1.34) and triacylglycerol lipase (EC 3.1.1.3), classified as analogous proteins in relation to H. sapiens enzymes, were identified as new potential molecular targets. PMID- 21034490 TI - Injuries to pedal cyclists on New Zealand roads, 1988-2007. AB - BACKGROUND: The risk of injury is one of the major barriers to engaging in cycling. We investigated exposure-based rates and profiles of traffic injuries sustained by pedal cyclists that resulted in death or hospital inpatient treatment in New Zealand, one of the most car dependent countries. METHODS: Pedal cyclist traffic injuries were identified from the Mortality Collection and the National Minimum Dataset. Total time spent cycling was used as the measure of exposure and computed from National Household Travel Surveys. Analyses were undertaken for the periods 1988-91, 1996-99 and 2003-07 in relation to other major road users and by age, gender and body region affected. A modified Barell matrix was used to characterise the profiles of pedal cyclist injuries by body region affected and nature of injury. RESULTS: Cyclists had the second highest rate of traffic injuries compared to other major road user categories and the rate increased from 1996-99 to 2003-07. During 2003-07, 31 injuries occurred per million hours spent cycling. Non-collision crashes (40%) and collisions with a car, pick-up truck or van (26%) accounted for two thirds of the cycling injuries. Children and adolescents aged under 15 years were at the highest risk, particularly of non-collision crashes. The rate of traumatic brain injuries fell from 1988-91 to 1996-99; however, injuries to other body parts increased steadily. Traumatic brain injuries were most common in collision cases whereas upper extremity fractures were most common in other crashes. CONCLUSIONS: The burden of fatal and hospitalised injuries among pedal cyclists is considerable and has been increasing over the last decade. This underscores the development of road safety and injury prevention programmes for cyclists alongside the cycling promotion strategies. PMID- 21034489 TI - HE3286, an oral synthetic steroid, treats lung inflammation in mice without immune suppression. AB - BACKGROUND: 17alpha-Ethynyl-5-androsten-3beta, 7beta, 17beta-triol (HE3286) is a synthetic derivative of an endogenous steroid androstenetriol (beta-AET), a metabolite of the abundant adrenal steroid deyhdroepiandrosterone (DHEA), with broad anti-inflammatory activities. We tested the ability of this novel synthetic steroid with improved pharmacological properties to limit non-productive lung inflammation in rodents and attempted to gauge its immunological impact. METHODS AND RESULTS: In mice, oral treatment with HE3286 (40 mg/kg) significantly (p < 0.05) decreased neutrophil counts and exudate volumes (~50%) in carrageenan induced pleurisy, and myeloperoxidase in lipopolysaccharide-induced lung injury. HE3286 (40 mg/kg) was not found to be profoundly immune suppressive in any of the classical animal models of immune function, including those used to evaluate antigen specific immune responses in vivo (ovalbumin immunization). When mice treated for two weeks with HE3286 were challenged with K. pneumoniae, nearly identical survival kinetics were observed in vehicle-treated, HE3286-treated and untreated groups. CONCLUSIONS: HE3286 represents a novel, first-in-class anti inflammatory agent that may translate certain benefits of beta-AET observed in rodents into treatments for chronic inflammatory pulmonary disease. PMID- 21034491 TI - Right ventricular exclusion for hepatocellular carcinoma metastatic to the heart. AB - We used for the first time a right ventricular exclusion procedure for the treatment of hepatocellular carcinoma metastatic to the right ventricle. Our case report shows that this surgical option can be effective as rescue therapy for right ventricular outflow tract obstruction secondary to myocardial metastasis in critically ill patients. Most notably, this technique can prevent inadvertent dislodgement of tumor cells. PMID- 21034492 TI - Implementing school malaria surveys in Kenya: towards a national surveillance system. AB - OBJECTIVE: To design and implement surveys of malaria infection and coverage of malaria control interventions among school children in Kenya in order to contribute towards a nationwide assessment of malaria. METHODS: The country was stratified into distinct malaria transmission zones based on a malaria risk map and 480 schools were visited between October 2008 and March 2010. Surveys were conducted in two phases: an initial opportunistic phase whereby schools were selected for other research purposes; and a second phase whereby schools were purposively selected to provide adequate spatial representation across the country. Consent for participation was based on passive, opt-out consent rather than written, opt-in consent because of the routine, low-risk nature of the survey. All children were diagnosed for Plasmodium infection using rapid diagnostic tests, assessed for anaemia and were interviewed about mosquito net usage, recent history of illness, and socio-economic and household indicators. Children's responses were entered electronically in the school and data transmitted nightly to Nairobi using a mobile phone modem connection. RDT positive results were corrected by microscopy and all results were adjusted for clustering using random effect regression modelling. RESULTS: 49,975 children in 480 schools were sampled, at an estimated cost of US$ 1,116 per school. The overall prevalence of malaria and anaemia was 4.3% and 14.1%, respectively, and 19.0% of children reported using an insecticide-treated net (ITN). The prevalence of infection showed marked variation across the country, with prevalence being highest in Western and Nyanza provinces, and lowest in Central, North Eastern and Eastern provinces. Nationally, 2.3% of schools had reported ITN use >60%, and low reported ITN use was a particular problem in Western and Nyanza provinces. Few schools reported having malaria health education materials or ongoing malaria control activities. CONCLUSION: School malaria surveys provide a rapid, cheap and sustainable approach to malaria surveillance which can complement household surveys, and in Kenya, show that large areas of the country do not merit any direct school-based control, but school-based interventions, coupled with strengthened community-based strategies, are warranted in western and coastal Kenya. The results also provide detailed baseline data to inform evaluation of school-based malaria control in Kenya. PMID- 21034493 TI - Gene expression analysis of cell death induction by taurolidine in different malignant cell lines. AB - BACKGROUND: The anti-infective agent Taurolidine (TRD) has been shown to have cell death inducing properties, but the mechanism of its action is largely unknown. The aim of this study was to identify potential common target genes modulated at the transcriptional level following TRD treatment in tumour cell lines originating from different cancer types. METHODS: Five different malignant cell lines (HT29, Chang Liver, HT1080, AsPC-1 and BxPC-3) were incubated with TRD (100 MUM, 250 MUM and 1000 MUM). Proliferation after 8 h and cell viability after 24 h were analyzed by BrdU assay and FACS analysis, respectively. Gene expression analyses were carried out using the Agilent-microarray platform to identify genes which displayed conjoint regulation following the addition of TRD in all cell lines. Candidate genes were subjected to Ingenuity Pathways Analysis and selected genes were validated by qRT-PCR and Western Blot. RESULTS: TRD 250 MUM caused a significant inhibition of proliferation as well as apoptotic cell death in all cell lines. Among cell death associated genes with the strongest regulation in gene expression, we identified pro-apoptotic transcription factors (EGR1, ATF3) as well as genes involved in the ER stress response (PPP1R15A), in ubiquitination (TRAF6) and mitochondrial apoptotic pathways (PMAIP1). CONCLUSIONS: This is the first conjoint analysis of potential target genes of TRD which was performed simultaneously in different malignant cell lines. The results indicate that TRD might be involved in different signal transduction pathways leading to apoptosis. PMID- 21034494 TI - Changing trends in blood transfusion in children and neonates admitted in Kilifi District Hospital, Kenya. AB - BACKGROUND: Severe anaemia is a common cause for hospitalization in children in sub-Saharan Africa. Malaria plays an important aetiological role, resulting in a substantial burden of paediatric transfusion in hospitals. A decline in malaria and paediatric admissions to the Kilifi District Hospital has been reported recently. This study aimed to investigate whether this trend affected clinical burden, clinical severity of anaemia and requirements for paediatric transfusion. METHODS: Eight-year retrospective review of paediatric admissions to Kilifi District Hospital, Kenya describing the frequency of moderate and severe anaemia, blood transfusion and case fatality over time. Definitions for severe anaemia were Hb <8 g/dl for newborns and <5 g/dl for other age groups and for moderate anaemia was Hb 8 to <11 g/dl for newborns and 5 to <9.3 g/dl for other age groups. Life threatening anaemia was defined as severe anaemia (Hb <5 g/dl) complicated by either deep breathing or prostration or profound anaemia (Hb <4 g/dl) alone. RESULTS: Of the 35,139 admissions 13,037 (37%) had moderate anaemia and 2,265 (6%) had severe anaemia; respiratory distress complicated 35% of cases with Hb <5 g/dl. Concurrent with the decline in malaria there was a marked decline in the prevalence of severe anaemia between 2002 (8%) and 2009 (< 4%) (chi2 for trend = 134, P < 0.0001). The number and proportion of admissions transfused also declined significantly over this time (chi2 for trend = 152, P < 0.0001). Of the 2,265 children with severe anaemia 191 (8%) died. Case fatality remained unchanged during this period (P < 0.26) and was largely explained by the unchanged proportion with life-threatening anaemia, present in 58-65% of cases throughout the study period. CONCLUSION: The impact of reduced malaria transmission on child morbidity has positive public benefits on the demand and use of blood for paediatric transfusion. Despite an overall reduction in paediatric transfusion requirement, case fatality of severe anaemia remained unchanged over this decade. Further research is required to improve outcome from severe anaemia, particularly in the high-risk group with life threatening features. PMID- 21034495 TI - Conjugated Linoleic Acid: good or bad nutrient. AB - Conjugated linoleic acid (CLA) is a class of 28 positional and geometric isomers of linoleic acid octadecadienoic.Currently, it has been described many benefits related to the supplementation of CLA in animals and humans, as in the treatment of cancer, oxidative stress, in atherosclerosis, in bone formation and composition in obesity, in diabetes and the immune system. However, our results show that, CLA appears to be not a good supplement in patients with cachexia. PMID- 21034496 TI - Sleep deprivation affects inflammatory marker expression in adipose tissue. AB - Sleep deprivation has been shown to increase inflammatory markers in rat sera and peripheral blood mononuclear cells. Inflammation is a condition associated with pathologies such as obesity, cancer, and cardiovascular diseases. We investigated changes in the pro and anti-inflammatory cytokines and adipokines in different depots of white adipose tissue in rats. We also assessed lipid profiles and serum levels of corticosterone, leptin, and adiponectin after 96 hours of sleep deprivation. METHODS: The study consisted of two groups: a control (C) group and a paradoxical sleep deprivation by 96 h (PSD) group. Ten rats were randomly assigned to either the control group (C) or the PSD. Mesenteric (MEAT) and retroperitoneal (RPAT) adipose tissue, liver and serum were collected following completion of the PSD protocol. Levels of interleukin (IL)-6, interleukin (IL)-10 and tumour necrosis factor (TNF)-alpha were analysed in MEAT and RPAT, and leptin, adiponectin, glucose, corticosterone and lipid profile levels were analysed in serum. RESULTS: IL-6 levels were elevated in RPAT but remained unchanged in MEAT after PSD. IL-10 protein concentration was not altered in either depot, and TNF-alpha levels decreased in MEAT. Glucose, triglycerides (TG), VLDL and leptin decreased in serum after 96 hours of PSD; adiponectin was not altered and corticosterone was increased. CONCLUSION: PSD decreased fat mass and may modulate the cytokine content in different depots of adipose tissue. The inflammatory response was diminished in both depots of adipose tissue, with increased IL-6 levels in RPAT and decreased TNF-alpha protein concentrations in MEAT and increased levels of corticosterone in serum. PMID- 21034497 TI - Trends in immunization completion and disparities in the context of health reforms: the case study of Tanzania. AB - BACKGROUND: Of global concern is the decline in under five children mortality which has reversed in some countries in sub Saharan Africa (SSA) since the early 1990 s which could be due to disparities in access to preventive services including immunization. This paper is aimed at determining the trend in disparities in completion of immunization using Tanzania Demographic and Health Surveys (DHS). METHODS: DHS studies randomly selected representative households from all regions in Tanzania since 1980 s, is repeated every five years in the same enumeration areas. The last three data sets (1990, 1996 and 2004) were downloaded and analyzed using STATA 9.0. The analysis included all children of between 12-23 months who would have completed all vaccinations required at 12 months. RESULTS: Across the time periods 1990, 1996 to 2004/05 the percentage of children completing vaccination was similar (71.0% in 1990, 72.7% in 1996 and 72.3% in 2005). There was no disparity in completion of immunization with wealth strata in 1990 and 1996 (p > 0.05) but not 2004. In 2004/05 there was marked disparity as most poor experienced significant decline in immunization completion while the least poor had significant increase (p < 0.001). All three periods children from households whose head had low education were less likely to complete immunization (p < 0.01). CONCLUSION: Equity that existed in 1990 and more pronounced in 1996 regressed to inequity in 2005, thus though at national level immunization coverage did not change, but at sub-group there was significant disparity associated with the changing contexts and reforms. To address sub-group disparities in immunization it is recommended to adopt strategies focused at governance and health system to reach all population groups and most poor. PMID- 21034498 TI - Exhaustive expansion: A novel technique for analyzing complex data generated by higher-order polychromatic flow cytometry experiments. AB - BACKGROUND: The complex data sets generated by higher-order polychromatic flow cytometry experiments are a challenge to analyze. Here we describe Exhaustive Expansion, a data analysis approach for deriving hundreds to thousands of cell phenotypes from raw data, and for interrogating these phenotypes to identify populations of biological interest given the experimental context. METHODS: We apply this approach to two studies, illustrating its broad applicability. The first examines the longitudinal changes in circulating human memory T cell populations within individual patients in response to a melanoma peptide (gp100209-2M) cancer vaccine, using 5 monoclonal antibodies (mAbs) to delineate subpopulations of viable, gp100-specific, CD8+ T cells. The second study measures the mobilization of stem cells in porcine bone marrow that may be associated with wound healing, and uses 5 different staining panels consisting of 8 mAbs each. RESULTS: In the first study, our analysis suggests that the cell surface markers CD45RA, CD27 and CD28, commonly used in historical lower order (2-4 color) flow cytometry analysis to distinguish memory from naive and effector T cells, may not be obligate parameters in defining central memory T cells (TCM). In the second study, we identify novel phenotypes such as CD29+CD31+CD56+CXCR4+CD90+Sca1-CD44+, which may characterize progenitor cells that are significantly increased in wounded animals as compared to controls. CONCLUSIONS: Taken together, these results demonstrate that Exhaustive Expansion supports thorough interrogation of complex higher-order flow cytometry data sets and aids in the identification of potentially clinically relevant findings. PMID- 21034499 TI - Prognostic significance of nuclear survivin expression in resected adenoid cystic carcinoma of the head and neck. AB - OBJECTIVES: The expression of survivin, an inhibitor of apoptosis, in tumor cells is associated with poor clinical outcome for various cancers. We conducted this study to determine survivin expression in patients with adenoid cystic carcinoma (ACC) of the head and neck and to identify its clinical significance as a prognostic factor. MATERIALS AND METHODS: We performed immunohistochemical staining for survivin, p53, bcl-2 protein, and Ki-67 in formalin fixed, paraffin embedded blocks from 37 cases of head and neck ACC. We also reviewed the patients' clinical records to determine the association of staining with clinical course. RESULTS: Of the 37 cases of head and neck ACC, 31 (83.8%) were positive for cytoplasmic survivin expression, and 23 (62.2%) were positive for nuclear survivin expression. There was a significant association between nuclear survivin expression and bcl-2 (P = 0.031). A larger tumor was more commonly a survivin positive tumor (cytoplasmic survivin, P = 0.043; nuclear survivin, P = 0.057). Median overall survival (OS) was significantly longer in patients not expressing nuclear survivin (P = 0.035). A multivariate analysis revealed that nuclear survivin expression significantly impacted OS (hazard ratio 8.567, P = 0.018) in addition to lymph node involvement (hazard ratio 7.704, P = 0.016). CONCLUSIONS: The immunohistochemical expression of nuclear survivin has a prognostic impact in patients with head and neck ACC. These results suggest that nuclear survivin expression may be a useful biomarker for predicting prognosis in patients with head and neck ACC who were treated with surgical resection. PMID- 21034500 TI - Fast growth associated with aberrant vasculature and hypoxia in fibroblast growth factor 8b (FGF8b) over-expressing PC-3 prostate tumour xenografts. AB - BACKGROUND: Prostate tumours are commonly poorly oxygenated which is associated with tumour progression and development of resistance to chemotherapeutic drugs and radiotherapy. Fibroblast growth factor 8b (FGF8b) is a mitogenic and angiogenic factor, which is expressed at an increased level in human prostate tumours and is associated with a poor prognosis. We studied the effect of FGF8b on tumour oxygenation and growth parameters in xenografts in comparison with vascular endothelial growth factor (VEGF)-expressing xenografts, representing another fast growing and angiogenic tumour model. METHODS: Subcutaneous tumours of PC-3 cells transfected with FGF8b, VEGF or empty (mock) vectors were produced and studied for vascularity, cell proliferation, glucose metabolism and oxygenation. Tumours were evaluated by immunohistochemistry (IHC), flow cytometry, use of radiolabelled markers of energy metabolism ([18F]FDG) and hypoxia ([18F]EF5), and intratumoral polarographic measurements of pO2. RESULTS: Both FGF8b and VEGF tumours grew rapidly in nude mice and showed highly vascularised morphology. Perfusion studies, pO2 measurements, [18F]EF5 and [18F]FDG uptake as well as IHC staining for glucose transport protein (GLUT1) and hypoxia inducible factor (HIF) 1 showed that VEGF xenografts were well-perfused and oxygenised, as expected, whereas FGF8b tumours were as hypoxic as mock tumours. These results suggest that FGF8b-induced tumour capillaries are defective. Nevertheless, the growth rate of hypoxic FGF8b tumours was highly increased, as that of well-oxygenised VEGF tumours, when compared with hypoxic mock tumour controls. CONCLUSION: FGF8b is able to induce fast growth in strongly hypoxic tumour microenvironment whereas VEGF-stimulated growth advantage is associated with improved perfusion and oxygenation of prostate tumour xenografts. PMID- 21034501 TI - Mis-reporting, previous health status and health status of family may seriously bias the association between food patterns and disease. AB - BACKGROUND: Food pattern analyses are popular tools in the study of associations between diet and health. However, there is a need for further evaluation of this methodology. The aim of the present cross-sectional study was to evaluate the relationship between food pattern groups (FPG) and existing health, and to identify factors influencing this relationship. METHODS: The inhabitants of Vasterbotten County in northern Sweden are invited to health check-ups when they turn 30, 40, 50, and 60 years of age. The present study includes data collected from almost 60,000 individuals between 1992 and 2005. Associations between FPG (established using K-means cluster analyses) and health were analyzed separately in men and women. RESULTS: The health status of the participants and their close family and reporting accuracy differed significantly between men and women and among FPG. Crude regression analyses, with the high fat FPG as reference, showed increased risks for several health outcomes for all other FPGs in both sexes. However, when limiting analysis to individuals without previous ill-health and with adequate energy intake reports, most of the risks instead showed a trend towards protective effects. CONCLUSIONS: Food pattern classifications reflect both eating habits and other own and family health related factors, a finding important to remember and to adjust for before singling out the diet as a primary cause for present and future health problems. Appropriate exclusions are suggested to avoid biases and attenuated associations in nutrition epidemiology. PMID- 21034502 TI - ADP-ribose polymer--a novel and general biomarker of human cancers of head & neck, breast, and cervix. AB - BACKGROUND: Poly-ADP-ribosylation, a reversible post-translational modification of primarily chromosomal proteins, is involved in various cellular and molecular processes including carcinogenesis. ADP-ribose polymer or poly-ADP-ribose adducts are enzymatically added onto or stripped off the target chromosomal proteins during this metabolic process. Due to this, the chromatin superstructure is reversibly altered, which significantly influences the pattern of gene expression. We hypothesize that a decrease in the concentration of total poly-ADP ribose adducts of peripheral blood lymphocyte (PBL) proteins strongly correlates with the incidence of human cancer. RESULTS: Using a novel immunoprobe assay, we show a statistically significant (P <= 0.001) reduction (~ 42 to 49%) in the level of poly-ADP-ribose adducts of PBL proteins of patients with advanced cancers of head & neck (H & N) region (comprising fourteen distinct cancers at different sites), breast and cervix in comparison to healthy controls. CONCLUSIONS: These findings imply potential utility of the poly-ADP-ribose adducts of PBL proteins as a novel and general biomarker of human cancers with potentials of significant clinical and epidemiological applications. PMID- 21034503 TI - Sentinel lymph node mapping by indocyanin green fluorescence imaging in oropharyngeal cancer - preliminary experience. AB - BACKGROUND: Sentinel lymph node (SLN) detection and biopsy is gaining popularity in the treatment of Head and Neck cancer. Various methods in this regard have been described, each with their respective advantages and disadvantages. The aim of this paper was to evaluate the potential application of Indocyanin Green (ICG) in the mapping and detection of sentinel lymph nodes (SLN) in cancers of the head and neck. METHODS: Patients with oropharyngeal cancer and N0 neck who were scheduled for primary tumor ablation as well as a neck dissection were selected. One milliliter of Indocyanin green was injected around the tumor and the sentinel node detection was performed by aiming the infra red video camera on the cervical area. When no detection was possible transcutaneously, a cervical incision was made, a sub-platysmal flap raised and further detection was done to visualize the fluorescing lymph nodes. RESULTS: Detection of cervical SLN was only possible when 5 mm or less tissue covered the sentinel lymph node. Accurate and clear detection of the lymph drainage pattern and SLN was possible. There is some uptake in other tissues such as the submandibular gland which is easily distinguishable from lymphatic tissue. CONCLUSION: Indocyanin green fluorescence is a potential valuable potential tool in the detection of SLN in patients with oropharyngeal cancer which warrants further investigation. PMID- 21034504 TI - pplacer: linear time maximum-likelihood and Bayesian phylogenetic placement of sequences onto a fixed reference tree. AB - BACKGROUND: Likelihood-based phylogenetic inference is generally considered to be the most reliable classification method for unknown sequences. However, traditional likelihood-based phylogenetic methods cannot be applied to large volumes of short reads from next-generation sequencing due to computational complexity issues and lack of phylogenetic signal. "Phylogenetic placement," where a reference tree is fixed and the unknown query sequences are placed onto the tree via a reference alignment, is a way to bring the inferential power offered by likelihood-based approaches to large data sets. RESULTS: This paper introduces pplacer, a software package for phylogenetic placement and subsequent visualization. The algorithm can place twenty thousand short reads on a reference tree of one thousand taxa per hour per processor, has essentially linear time and memory complexity in the number of reference taxa, and is easy to run in parallel. Pplacer features calculation of the posterior probability of a placement on an edge, which is a statistically rigorous way of quantifying uncertainty on an edge-by-edge basis. It also can inform the user of the positional uncertainty for query sequences by calculating expected distance between placement locations, which is crucial in the estimation of uncertainty with a well-sampled reference tree. The software provides visualizations using branch thickness and color to represent number of placements and their uncertainty. A simulation study using reads generated from 631 COG alignments shows a high level of accuracy for phylogenetic placement over a wide range of alignment diversity, and the power of edge uncertainty estimates to measure placement confidence. CONCLUSIONS: Pplacer enables efficient phylogenetic placement and subsequent visualization, making likelihood-based phylogenetics methodology practical for large collections of reads; it is freely available as source code, binaries, and a web service. PMID- 21034505 TI - Unicameral bone cyst of the lunate in an adult: case report. AB - We report a case of a symptomatic unicameral (simple) bone cyst of the lunate in a 42-year- old woman. The lesion was treated with curettage and cancellous autogenous iliac bone grafting. At five years of follow-up the wrist was pain free, there were no limitations of motion, and the radiographs showed complete obliteration of the cavity. To the best of our knowledge, no other unicameral bone cyst of the lunate has been reported in an adult. Cysts with significant cavities at the carpal bones in an adult should be approached cautiously, as they may require early curettage and bone grafting for healing, before collapse and degenerative changes occur. PMID- 21034506 TI - Predictors of adherence to antiretroviral therapy among people living with HIV/AIDS in resource-limited setting of southwest ethiopia. AB - BACKGROUND: Good adherence to antiretroviral therapy is necessary to achieve the best virological response, lower the risk that drug resistance will develop, and reduce morbidity and mortality. Little is known about the rate and predictors of adherence in Ethiopia. Therefore this study determines the magnitude and predictors of adherence to antiretroviral therapy among people living with HIV/AIDS in Southwest Ethiopia. METHODS: A cross sectional study was carried out from January 1, 2009 to March 3, 2009 among 319 adult PLWHA (>= 18 years) attending ART clinic at Jimma university Specialized Hospital (JUSH). Multiple Logistic regression models were constructed with adherence and independent variables to identify the predictors. RESULTS: About 303(95%) of the study subjects were adherent based on self report of missed doses (dose adherence) in a one-week recall before the actual interview. The rate of self reported adherence in the study based on the combined indicator of the dose, time and food adherence measurement was 72.4%. Patients who got family support were 2 times [2.12(1.25 3.59)] more likely to adhere than those who didn't get family support as an independent predictor of overall adherence (dose, time and food). The reasons given for missing drugs were 9(27.3%) running out of medication/drug, 7(21.2%) being away from home and 7(21.2%) being busy with other things. CONCLUSION: The adherence rate found in this study is similar to other resource limited setting and higher than the developed country. This study highlights emphasis should be given for income generating activities and social supports that helps to remember the patients for medication taking and management of opportunistic infections during the course of treatment. PMID- 21034507 TI - Basal and adrenocorticotropic hormone stimulated plasma cortisol levels among Egyptian autistic children: relation to disease severity. AB - BACKGROUND: Autism is a disorder of early childhood characterized by social impairment, communication abnormalities and stereotyped behaviors. The hypothalamic-pituitary-adrenocortical (HPA) axis deserves special attention, since it is the basis for emotions and social interactions that are affected in autism. AIM: To assess basal and stimulated plasma cortisol, and adrenocorticotropic hormone (ACTH) levels in autistic children and their relationship to disease characteristics. METHODS: Fifty autistic children were studied in comparison to 50 healthy age-, sex- and pubertal stage- matched children. All subjects were subjected to clinical evaluation and measurement of plasma cortisol (basal and stimulated) and ACTH. In addition, electroencephalography (EEG) and intelligence quotient (IQ) assessment were done for all autistic children. RESULTS: Sixteen% of autistic patients had high ACTH, 10% had low basal cortisol and 10% did not show adequate cortisol response to ACTH stimulation. Autistic patients had lower basal (p = 0.032) and stimulated cortisol (p = 0.04) and higher ACTH (p = 0.01) than controls. Childhood Autism Rating Scale (CARS) score correlated positively with ACTH (r = 0.71, p = 0.02) and negatively with each of basal (r = -0.64, p = 0.04) and stimulated cortisol (r = -0.88, p < 0.001). Hormonal profile did not differ in relation to EEG abnormalities, IQ and self- aggressive symptoms. CONCLUSIONS: The observed hormonal changes may be due to a dysfunction in the HPA axis in autistic individuals. Further studies are warranted regarding the role of HPA axis dysfunction in the pathogenesis of autism. PMID- 21034508 TI - Potential pitfalls in MitoChip detected tumor-specific somatic mutations: a call for caution when interpreting patient data. AB - BACKGROUND: Several investigators have employed high throughput mitochondrial sequencing array (MitoChip) in clinical studies to search mtDNA for markers linked to cancers. In consequence, a host of somatic mtDNA mutations have been identified as linked to different types of cancers. However, closer examination of these data show that there are a number of potential pitfalls in the detection tumor-specific somatic mutations in clinical case studies, thus urging caution in the interpretation of mtDNA data to the patients. This study examined mitochondrial sequence variants demonstrated in cancer patients, and assessed the reliability of using detected patterns of polymorphisms in the early diagnosis of cancer. METHODS: Published entire mitochondrial genomes from head and neck, adenoid cystic carcinoma, sessile serrated adenoma, and lung primary tumor from clinical patients were examined in a phylogenetic context and compared with known, naturally occurring mutations which characterize different populations. RESULTS: The phylogenetic linkage analysis of whole arrays of mtDNA mutations from patient cancerous and non-cancerous tissue confirmed that artificial recombination events occurred in studies of head and neck, adenoid cystic carcinoma, sessile serrated adenoma, and lung primary tumor. Our phylogenetic analysis of these tumor and control leukocyte mtDNA haplotype sequences shows clear cut evidence of mixed ancestries found in single individuals. CONCLUSIONS: Our study makes two prescriptions: both in the clinical situation and in research 1. more care should be taken in maintaining sample identity and 2. analysis should always be undertaken with respect to all the data available and within an evolutionary framework to eliminate artifacts and mix-ups. PMID- 21034509 TI - Pattern of fractures across pediatric age groups: analysis of individual and lifestyle factors. AB - BACKGROUND: Knowledge of the epidemiology of children's fractures is essential to develop preventive strategies. The aim of this study was to analyze the individual/lifestyle determinants of fractures across pediatric age groups. METHODS: A cross-sectional study was performed in the first six months of 2008 through questionnaire on a sample of children from an outpatient clinic for pediatric fractures. Differences in gender, anatomic site, circumstances and location of fracture occurrence, behavioural lifestyle, and calcium intake were investigated among three different age classes (pre-school children, school children, and adolescents). RESULTS: The sample consisted of 382 subjects (2-14 years of age) sustaining a fracture after low or moderate trauma. Males were at a higher risk of fractures than females; greater than two-thirds of injuries occurred after low-energy trauma and the upper limb was more frequently involved. With increasing age, the male/female ratio and time spent in sports participation increased (p < 0.001), while calcium intake and time spent in sedentary behaviors decreased (p < 0.001 and < 0.003, respectively). Gender discordance existed in pre-school children with respect to the anatomic location, and in school children and adolescents with respect to the dynamics. In the adolescent group, males were more physically active and also more sedentary than females. Fractures most frequently occurred in homes (41.6%), followed by playgrounds and footpaths (26.2%), sports facilities (18.3%), and educational facilities (13.9%), with gender differences existing only in adolescence. Twenty-three percent of the subjects sustained one or more fractures in the past. The percentage of recurrent fractures increased with age (p = 0.001), with a similar trend in both genders. CONCLUSIONS: Gender differences were shown in the prevalence of injuries, characteristics, and circumstances across ages. These differences may be explained by the related changes in behaviors, together with attending different places. Individual and lifestyle factors can in part explain the variability in the occurrence of fractures and can also address targeted preventive strategies. PMID- 21034510 TI - Detection of copy number variation from array intensity and sequencing read depth using a stepwise Bayesian model. AB - BACKGROUND: Copy number variants (CNVs) have been demonstrated to occur at a high frequency and are now widely believed to make a significant contribution to the phenotypic variation in human populations. Array-based comparative genomic hybridization (array-CGH) and newly developed read-depth approach through ultrahigh throughput genomic sequencing both provide rapid, robust, and comprehensive methods to identify CNVs on a whole-genome scale. RESULTS: We developed a Bayesian statistical analysis algorithm for the detection of CNVs from both types of genomic data. The algorithm can analyze such data obtained from PCR-based bacterial artificial chromosome arrays, high-density oligonucleotide arrays, and more recently developed high-throughput DNA sequencing. Treating parameters--e.g., the number of CNVs, the position of each CNV, and the data noise level--that define the underlying data generating process as random variables, our approach derives the posterior distribution of the genomic CNV structure given the observed data. Sampling from the posterior distribution using a Markov chain Monte Carlo method, we get not only best estimates for these unknown parameters but also Bayesian credible intervals for the estimates. We illustrate the characteristics of our algorithm by applying it to both synthetic and experimental data sets in comparison to other segmentation algorithms. CONCLUSIONS: In particular, the synthetic data comparison shows that our method is more sensitive than other approaches at low false positive rates. Furthermore, given its Bayesian origin, our method can also be seen as a technique to refine CNVs identified by fast point-estimate methods and also as a framework to integrate array-CGH and sequencing data with other CNV-related biological knowledge, all through informative priors. PMID- 21034512 TI - Research workshop to research work: initial steps in establishing health research systems on Malaita, Solomon Islands. AB - INTRODUCTION: Atoifi Adventist Hospital is a 90 bed general hospital in East Kwaio, Malaita, Solomon Islands providing services to the population of subsistence villagers of the region. Health professionals at the hospital and attached College of Nursing have considerable human capacity and willingness to undertake health research. However they are constrained by limited research experience, training opportunities, research systems, physical infrastructure and access to resources. This brief commentary describes an 'Introduction to Health Research' workshop delivered at Atoifi Adventist Hospital in September 2009 and efforts to move from 'research workshop' to 'research work'. THE APPROACH: Using a participatory-action research approach underpinned by decolonising methodologies, staff from Atoifi Adventist Hospital and James Cook University (Queensland, Australia) collaboratively designed, implemented and evaluated a health research workshop. Basic health research principles and methods were presented using active learning methodologies. Following the workshop, Atoifi Adventist Hospital and Atoifi College of Nursing staff, other professionals and community members reported an increased awareness and understanding of health research. The formation of a local Research Committee, improved ethics review procedures and the identification of local research mentors followed the week long workshop. The workshop has acted as a catalyst for research activity, increasing structural and human resource capacity for local health professionals and community leaders to engage in research. DISCUSSION AND CONCLUSIONS: Participants from a variety of educational backgrounds participated in, and received benefit from, a responsive, culturally and linguistically accessible health research workshop. Improving health research systems at a remote hospital and aligning these with local and national research agendas is establishing a base to strengthen public health research and practice on Malaita, Solomon Islands. PMID- 21034511 TI - Pro-inflammatory cytokines derived from West Nile virus (WNV)-infected SK-N-SH cells mediate neuroinflammatory markers and neuronal death. AB - BACKGROUND: WNV-associated encephalitis (WNVE) is characterized by increased production of pro-inflammatory mediators, glial cells activation and eventual loss of neurons. WNV infection of neurons is rapidly progressive and destructive whereas infection of non-neuronal brain cells is limited. However, the role of neurons and pathological consequences of pro-inflammatory cytokines released as a result of WNV infection is unclear. Therefore, the objective of this study was to examine the role of key cytokines secreted by WNV-infected neurons in mediating neuroinflammatory markers and neuronal death. METHODS: A transformed human neuroblastoma cell line, SK-N-SH, was infected with WNV at multiplicity of infection (MOI)-1 and -5, and WNV replication kinetics and expression profile of key pro-inflammatory cytokines were analyzed by plaque assay, qRT-PCR, and ELISA. Cell death was measured in SK-N-SH cell line in the presence and absence of neutralizing antibodies against key pro-inflammatory cytokines using cell viability assay, TUNEL and flow cytometry. Further, naive primary astrocytes were treated with UV-inactivated supernatant from mock- and WNV-infected SK-N-SH cell line and the activation of astrocytes was measured using flow cytometry and ELISA. RESULTS: WNV-infected SK-N-SH cells induced the expression of IL-1beta, 6, -8, and TNF-alpha in a dose- and time-dependent manner, which coincided with increase in virus-induced cell death. Treatment of cells with anti-IL-1beta or TNF-alpha resulted in significant reduction of the neurotoxic effects of WNV. Furthermore treatment of naive astrocytes with UV-inactivated supernatant from WNV-infected SK-N-SH cell line increased expression of glial fibrillary acidic protein and key inflammatory cytokines. CONCLUSION: Our results for the first time suggest that neurons are one of the potential sources of pro-inflammatory cytokines in WNV-infected brain and these neuron-derived cytokines contribute to WNV-induced neurotoxicity. Moreover, cytokines released from neurons also mediate the activation of astrocytes. Our data define specific role(s) of WNV-induced pro inflammatory cytokines and provide a framework for the development of anti inflammatory drugs as much-needed therapeutic interventions to limit symptoms associated with WNVE. PMID- 21034513 TI - Lobaplatin arrests cell cycle progression in human hepatocellular carcinoma cells. AB - BACKGROUND: Hepatocellular carcinoma (HCC) still is a big burden for China. In recent years, the third-generation platinum compounds have been proposed as potential active agents for HCC. However, more experimental and clinical data are warranted to support the proposal. In the present study, the effect of lobaplatin was assessed in five HCC cell lines and the underlying molecular mechanisms in terms of cell cycle kinetics were explored. METHODS: Cytotoxicity of lobaplatin to human HCC cell lines was examined using MTT cell proliferation assay. Cell cycle distribution was determined by flow cytometry. Expression of cell cycle regulated genes was examined at both the mRNA (RT-PCR) and protein (Western blot) levels. The phosphorylation status of cyclin-dependent kinases (CDKs) and retinoblastoma (Rb) protein was also examined using Western blot analysis. RESULTS: Lobaplatin inhibited proliferation of human HCC cells in a dose dependent manner. For the most sensitive SMMC-7721 cells, lobaplatin arrested cell cycle progression in G1 and G2/M phases time-dependently which might be associated with the down-regulation of cyclin B, CDK1, CDC25C, phosphorylated CDK1 (pCDK1), pCDK4, Rb, E2F, and pRb, and the up-regulation of p53, p21, and p27. CONCLUSION: Cytotoxicity of lobaplatin in human HCC cells might be due to its ability to arrest cell cycle progression which would contribute to the potential use of lobaplatin for the management of HCC. PMID- 21034514 TI - Podoplanin in cancer cells is experimentally able to attenuate prolymphangiogenic and lymphogenous metastatic potentials of lung squamoid cancer cells. AB - BACKGROUND: Podoplanin, a mucin-like transmembrane glycoprotein, is reportedly expressed in a variety of malignant cells and is generally regarded as a factor for promoting tumor progression in conventional studies. By contrast, a clinicopathologically conflicting role for podoplanin, namely as a favorable prognostic factor for patients with lung/cervical squamous cell carcinoma (SCC), has recently been reported. Here, we investigated the role of podoplanin expressed in lung squamoid cancer cells (LSCCs) in experimental tumor progression. RESULTS: Using EBC-1 cells, a lung SCC cell line without podoplanin expression and with lymphogenous metastatic potential, stable transformants with or without an exogenous human podoplanin gene were established and applied to a mouse tumor implantation model. In vivo examinations revealed that exogenous podoplanin had no influence on tumor growth, whereas it significantly restrained axillary lymph node metastasis associated with the suppression of lymphangiogenesis but not angiogenesis and with the downregulation of EBC-1 derived VEGF-C but not other lymphangiogenesis-related factor mRNAs in implanted tumor tissue. In vitro examinations to clarify the mechanisms underlying the in vivo phenomena revealed that exogenous podoplanin significantly suppressed the expression of VEGF-C mRNA and of the protein, and also increased the level of phosphorylated c-jun N terminal kinase (JNK) in EBC-1 cells. The former effect of exogenous podoplanin was impaired by treatment with either JNK inhibitor sp600125 or podoplanin-siRNA, and the latter effect was impaired by treatment with podoplanin-siRNA, suggesting that podoplanin was able to activate JNK, thereby downregulating VEGF-C gene expression in LSCCs (podoplanin-JNK-VEGF-C axis). Furthermore, supporting evidence in regard to the axis present in LSCCs was obtained from similar experiments using H157 cells, another lung SCC cell line expressing endogenous podoplanin. CONCLUSIONS: Our findings suggested that LSCC associated podoplanin was functional and could attenuate the potential for lymph node metastasis, possibly based on the suppression of tumor lymphangiogenesis; thus, podoplanin in cancer cells may become a useful biomarker to measure the malignancy of lung SCC. PMID- 21034516 TI - Bilateral heterochronic spontaneous hemothorax caused by pulmonary arteriovenous malformation in a gravid: a case report. AB - Bilateral heterochronic spontaneous hemothorax as a result of pulmonary arteriovenous malformation is a very rarely happened disease. A 34-year-old woman presented major symptoms with right-sided chest pain and shortness of breath. The following contrast-enhanced computed tomographic scan of the chest showed a large amount of fluid in the right thorax with mediastinal shift, but without major vessel injury and 2 small dense opacities in the apical segment of the right lower lobe and in the posterior aspect of the left lower lobe. The patient underwent local resection of the right lower lobe. The pulmonary arteriovenous malformation was further identified by pathological examination. One month after she was discharged home, the symptoms described above recurred. A follow-up computed tomographic scan of the chest showed a large amount of fluid in the left thorax. During the emergency operation, we found a bullous lesion in the left lower lobe and a small blood vessel overlying the lesion that was actively bleeding. As stated above, local resection of the left lower lobe was performed once more. Pathological result was the same as observed previously. There were no postoperative complications and she was discharged from the hospital after two weeks. Two months later, she successfully delivered a healthy female infant. Up to now, regular follow-up observation has shown her to be perfectly asymptomatic. PMID- 21034515 TI - Sox10-Venus mice: a new tool for real-time labeling of neural crest lineage cells and oligodendrocytes. AB - BACKGROUND: While several mouse strains have recently been developed for tracing neural crest or oligodendrocyte lineages, each strain has inherent limitations. The connection between human SOX10 mutations and neural crest cell pathogenesis led us to focus on the Sox10 gene, which is critical for neural crest development. We generated Sox10-Venus BAC transgenic mice to monitor Sox10 expression in both normal development and in pathological processes. RESULTS: Tissue fluorescence distinguished neural crest progeny cells and oligodendrocytes in the Sox10-Venus mouse embryo. Immunohistochemical analysis confirmed that Venus expression was restricted to cells expressing endogenous Sox10. Time-lapse imaging of various tissues in Sox10-Venus mice demonstrated that Venus expression could be visualized at the single-cell level in vivo due to the intense, focused Venus fluorescence. In the adult Sox10-Venus mouse, several types of mature and immature oligodendrocytes along with Schwann cells were clearly labeled with Venus, both before and after spinal cord injury. CONCLUSIONS: In the newly developed Sox10-Venus transgenic mouse, Venus fluorescence faithfully mirrors endogenous Sox10 expression and allows for in vivo imaging of live cells at the single-cell level. This Sox10-Venus mouse will thus be a useful tool for studying neural crest cells or oligodendrocytes, both in development and in pathological processes. PMID- 21034517 TI - Field optimization of the sex pheromone of Stenoma catenifer (Lepidoptera: Elachistidae): evaluation of lure types, trap height, male flight distances, and number of traps needed per avocado orchard for detection. AB - The sex pheromone of Stenoma catenifer was evaluated in commercial avocado orchards in Guatemala to determine operational parameters, such as optimal lure type, trap height, trap density and estimates of the distances that male moths fly. Of four pheromone dispensers tested, gray and white rubber septa were of equal efficacy, whereas 1-ml low-density polyethylene vials and 2*3-cm polyethylene ziplock bags were least efficacious. The height at which wing traps were hung did not significantly affect the number of adult male S. catenifer captured. For monitoring S. catenifer, these data suggest that the pheromone should be dispensed from gray rubber septa in wing traps hung inside the tree canopy at 1.75 m, a height convenient for trap placement and monitoring. Mark recapture studies of male S. catenifer indicated that, on average, males flew 67 m in one night. However, it is likely that this is an underestimate of the distance that male moths are capable of flying in a single night. Probabilistic modeling of S. catenifer capture data from different numbers of pheromone traps deployed in seven commercial avocado orchards of varying sizes and infestation levels suggested that 10-13 randomly deployed traps per orchard for a 7-day period are needed to detect at least one male S. catenifer with 90% confidence. These data provide sufficient information to develop effective protocols for using the S. catenifer pheromone to detect and monitor this pest in countries with endemic populations that are exporting fresh avocados, and for quarantine detection and incursion monitoring in countries receiving avocado imports from high risk areas. PMID- 21034518 TI - Genetic variability in esterases and the insecticide resistance in brazilian strains of Oryzaephilus mercator and Oryzaephilus surinamensis (Coleoptera: Silvanidae). AB - Oryzaephilus mercator and O. surinamensis are stored grains and processed food pests, the latter being responsible for major economical losses. Polyacrylamide gel electrophoresis was used to analyse esterase patterns during insect development. Seven esterases, three cholinesterases, two carboxylesterases and two acetylesterases, were identified in O. mercator, one of which was proper to adults. Five esterases, of which four were cholinesterases, occurred in O. surinamensis. Strains of O. mercator and O. surinamensis were also exposed to malathion and chlorpyrifos-methyl. According to the LC50 estimates, OmLC-M and OmLA strains of O. mercator and OsLB strain of O. surinamensis were the most resistant to both insecticides. However, higher sensitivity to malathion and chlorpyrifos-methyl has also been verified in some of its esterases. Cholinesterases OmEST-1 and OsEST-5 seem to be involved in this resistance. These results suggest that organophosphate tolerance may be related to genetic variability in esterase isoenzymes. PMID- 21034519 TI - PCR-based species identification of Agriotes larvae. AB - Click beetle larvae within the genus Agriotes (Coleoptera: Elateridae), commonly known as wireworms, are abundant ground-dwelling herbivores which can inflict considerable damage to field crops. In Central Europe up to 20 species, which differ in their distribution, ecology and pest status, occur in arable land. However, the identification of these larvae based on morphological characters is difficult or impossible. This hampers progress towards controlling these pests. Here, we present a polymerase chain reaction (PCR)-based approach to identify, for the first time, 17 Agriotes species typically found in Central Europe. Diagnostic sequence information was generated and submitted to GenBank, allowing the identification of these species via DNA barcoding. Moreover, multiplex PCR assays were developed to identify the nine most abundant species rapidly within a single-step reaction: Agriotes brevis, A. litigiosus, A. obscurus, A. rufipalpis, A. sordidus, A. sputator, A. ustulatus, A. lineatus and A. proximus. The latter two species remain molecularly indistinguishable, questioning their species status. The multiplex PCR assays proved to be highly specific against non agrioted elaterid beetles and other non-target soil invertebrates. By testing the molecular identification system with over 900 field-collected larvae, our protocol proved to be a reliable, cheap and quick method to routinely identify Central European Agriotes species. PMID- 21034520 TI - Crop and field boundary influences on the activity of a wide range of beneficial invertebrate groups on a split conventional/organic farm in northern England. AB - Activity of 12 beneficial invertebrate groups was assessed in 2005 and 2006 on a farm in northern England split into conventional and organic management halves, using pitfall and pan traps set in both crops and field boundaries. Management, crop and boundary structure influences on invertebrate activity were assessed, as was the relationship between crop and boundary type. Classification of crop and boundary assemblages produced three and two groups, respectively, in both years. Organic arable crops had well-defined assemblages in both years; and, while grass and grass/clover fields were separated from conventional arable fields in 2005, there was mixing in 2006. One boundary group, in both years, was dominated by conventional arable fields with tall herbaceous boundary vegetation. The other group had more organic arable and grassy fields with shorter boundary vegetation. Redundancy analyses showed that a number of groups (Cantharidae, Coccinellidae, Syrphidae, Ichneumonidae, Braconidae, Proctotrupoidea, Lycosidae) were more active in organic arable fields with more Staphylinidae in conventional arable crops and no obvious trend with Carabidae, Hemiptera, Neuroptera and Linyphiidae. Activity of some groups, especially Coccinellidae, Syrphidae and parasitic wasps, was strongly related to weed cover. Staphylinidae were most active in tall herbaceous boundaries by conventional arable crops with more of a number of groups (Cantharidae, Coccinellidae, parasitic wasps) in short herbaceous boundaries by organic arable crops. Organic management produced most differences in aerially-dispersed invertebrates, and management had a profound effect on activity in field boundaries. Possible management prescriptions to increase invertebrate activity include changing sowing times, weed cover manipulation and field boundary and margin management. PMID- 21034521 TI - Reproductive incompatibility between the B and Q biotypes of the whitefly Bemisia tabaci in China: genetic and behavioural evidence. AB - The B and Q 'biotypes' of Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae) have been invading many parts of the world and causing severe damage to a range of crops. Recent phylogenetic analyses indicate that B and Q are cryptic species within the B. tabaci species complex. Although various attempts have been made to examine the reproductive compatibility between B and Q, few studies have tested the fertility of the F1 females and so the extent of possible gene flow remains unclear. In this study, we conducted a series of crossing experiments and behavioural observations to examine in detail the reproductive compatibility between the B and Q biotypes collected from Zhejiang, China, a region recently invaded by these whiteflies. Crossing experiments between the two biotypes using either single-pairs or small groups demonstrated that proportions of females in the F1 progeny were only 0-2% in the inter-biotype crosses compared to 58-68% in the intra-biotype treatments. Furthermore, all inter-biotype F1 females were sterile. Continuous video observations showed that B and Q adults very rarely copulated, and copulation occurred only when adults of opposite sex from different biotypes were enclosed in dense cohorts for a relatively long period of time. These data show that the B and Q biotypes examined in this study are completely isolated in reproduction. The isolation was due to mainly a copulation barrier, but post-copulation barriers were also involved. PMID- 21034522 TI - Edge-induced narrowing of dietary diversity in leaf-cutting ants. AB - Much of the ecological alteration faced by human-modified Neotropical forests can be assigned to edge effects, including the proliferation of some voracious herbivores such as leaf-cutting ants. However, the underlying mechanisms/impacts of tropical forest edge on herbivores performance and their foraging behaviour (e.g. dietary diversity) have rarely been investigated. The goal of this study was, therefore, to determine whether and how the annual diet (i.e. species richness, diversity and the relative proportion of pioneer versus non-pioneer species of plant materials) of Atta cephalotes colonies differs in the forest edge versus the interior zone of a large remnant of Atlantic forest in northeastern Brazil. Among the key results was a strong habitat effect on dietary diversity (explaining ca. 40-50% of the variation), which, in edge colonies, decreased approximately by one fourth compared to interior colonies (inverse of Simpson's index: 3.7+/-0.84 versus 4.99+/-0.95). There was a predominance of leaf fragments collected from pioneer species in the diet in both habitat (86% in edge and 80.4% in interior). Edge colonies collected proportionally more fragments from pioneer species than colonies located in the forest interior. Our results are the first to demonstrate an edge-mediated relaxation of dietary restrictions in leaf-cutting ants. These findings render robust support to previous evidence indicating the reduction of bottom-up forces as a key factor explaining both edge induced hyper-abundance and increased herbivory of leaf-cutting ants in human modified Neotropical landscapes. PMID- 21034524 TI - Does size matter? Subsegmental cues to vowel mispronunciation detection. AB - Children look longer at a familiar object when presented with either correct pronunciations or small mispronunciations of consonants in the object's label, but not following larger mispronunciations. The current article examines whether children display a similar graded sensitivity to different degrees of mispronunciations of the vowels in familiar words, by testing children's sensitivity to 1-feature, 2-feature and 3-feature mispronunciations of the vowels of familiar labels: Children aged 1 ; 6 did not show a graded sensitivity to vowel mispronunciations, even when the trial length was increased to allow them more time to form a response. Two-year-olds displayed a robust sensitivity to increases in vowel mispronunciation size, differentiating between small and large mispronunciations. While this suggests that early lexical representations contain information about the features contributing to vocalic identity, we present evidence that this graded sensitivity is better explained by the acoustic characteristics of the different mispronunciation types presented to children. PMID- 21034523 TI - Bt-toxin uptake by the non-target herbivore, Myzus persicae (Hemiptera: Aphididae), feeding on transgenic oilseed rape in laboratory conditions. AB - The potential non-target effects of genetically modified crops are some of the more debated topics within applied biotechnologies in agriculture and environmental risk assessment. The objective of the present research was to study the potential Bt-toxin uptake by the non-target herbivore Myzus persicae Sulzer (Hemiptera: Aphididae) feeding on transgenic oilseed rape plants (Brassica napus cv. 'Westar' lines GT 2-4) expressing the Cry1Ac endotoxin. A specific aim was to replicate our previous experiment in controlled laboratory conditions to avoid or minimize the risk of contamination leading to potential false positive results. The toxin levels in vernalized (V) and not-vernalized (not-V) transgenic oilseed rape plants was also monitored to better clarify the role of physiological processes on Bt-toxin expression. Cry1Ac expression in not-V plants (mean concentration+/-SE=167.8+/-5.7 MUg kg-1 FW) showed a pattern of large variability, in comparison with V plants whose expression (mean concentration+/ SE=227.7+/-1.9 MUg kg-1 FW) was significantly more stable. Cry1Ac toxin was detected in three aphid samples reared on V plants with a mean toxin concentration+/-SE of 4.8+/-0.6 MUg Kg-1 FW and in three out of six samples of aphids reared on not-V plants (mean toxin concentration+/-SE=7.1+/-1.2 MUg kg-1 FW). The mean Bt-toxin concentration of all the positive aphid samples was 5.9+/ 1.0 MUg kg-1 FW. Our results confirmed the findings of our previous experiment and highlighted the potential for Cry1Ac toxin uptake by aphids feeding on transgenic oilseed rape plants. PMID- 21034525 TI - Overview of personalized medicine in the disease genomic era. AB - Sir William Osler (1849-1919) recognized that "variability is the law of life, and as no two faces are the same, so no two bodies are alike, and no two individuals react alike and behave alike under the abnormal conditions we know as disease". Accordingly, the traditional methods of medicine are not always best for all patients. Over the last decade, the study of genomes and their derivatives (RNA, protein and metabolite) has rapidly advanced to the point that genomic research now serves as the basis for many medical decisions and public health initiatives. Genomic tools such as sequence variation, transcription and, more recently, personal genome sequencing enable the precise prediction and treatment of disease. At present, DNA-based risk assessment for common complex diseases, application of molecular signatures for cancer diagnosis and prognosis, genome-guided therapy, and dose selection of therapeutic drugs are the important issues in personalized medicine. In order to make personalized medicine effective, these genomic techniques must be standardized and integrated into health systems and clinical workflow. In addition, full application of personalized or genomic medicine requires dramatic changes in regulatory and reimbursement policies as well as legislative protection related to privacy. This review aims to provide a general overview of these topics in the field of personalized medicine. PMID- 21034526 TI - Epigenetic modification is linked to Alzheimer's disease: is it a maker or a marker? AB - Alzheimer's disease (AD) is the most common age-dependent neurodegenerative disorder and shows progressive memory loss and cognitive decline. Intraneuronal filaments composed of aggregated hyperphosphorylated tau protein, called neurofibrillary tangles, along with extracellular accumulations of amyloid beta protein (Abeta), called senile plaques, are known to be the neuropathological hallmarks of AD. In light of recent studies, epigenetic modification has emerged as one of the pathogenic mechanisms of AD. Epigenetic changes encompass an array of molecular modifications to both DNA and chromatin, including transcription factors and cofactors. In this review, we summarize how DNA methylation and changes to DNA chromatin packaging by post-translational histone modification are involved in AD. In addition, we describe the role of SIRTs, histone deacetylases, and the effect of SIRT-modulating drugs on AD. Lastly, we discuss how amyloid precursor protein (APP) intracellular domain (AICD) regulates neuronal transcription. Our understanding of the epigenomes and transcriptomes of AD may warrant future identification of novel biological markers and beneficial therapeutic targets for AD. PMID- 21034527 TI - Possible roles of amyloid intracellular domain of amyloid precursor protein. AB - Amyloid precursor protein (APP), which is critically involved in the pathogenesis of Alzheimer's disease (AD), is cleaved by gamma/epsilon-secretase activity and results in the generation of different lengths of the APP Intracellular C terminal Domain (AICD). In spite of its small size and short half-life, AICD has become the focus of studies on AD pathogenesis. Recently, it was demonstrated that AICD binds to different intracellular binding partners ('adaptor protein'), which regulate its stability and cellular localization. In terms of choice of adaptor protein, phosphorylation seems to play an important role. AICD and its various adaptor proteins are thought to take part in various cellular events, including regulation of gene transcription, apoptosis, calcium signaling, growth factor, and NF-kappaB pathway activation, as well as the production, trafficking, and processing of APP, and the modulation of cytoskeletal dynamics. This review discusses the possible roles of AICD in the pathogenesis of neurodegenerative diseases including AD. PMID- 21034528 TI - Evaluation of chemopreventive effects of Thymoquinone on cell surface glycoconjugates and cytokeratin expression during DMBA induced hamster buccal pouch carcinogenesis. AB - The present study aimed to investigate the membrane stabilizing effect of Thymoquinone (TQ) on cell surface glycoconjugates and cytokeratin expression against DMBA induced hamster buccal pouch carcinogenesis. 0.5% DMBA painting (three times per week) in hamster buccal pouches for 14 weeks resulted in the formation of well developed oral squamous cell carcinoma. We observed 100% tumor formation with marked abnormalities of glycoconjugates status in tumor bearing hamsters as compared to control animals. Oral administration of TQ at a dose of 30 mg/kg body weight, to DMBA painted hamsters on alternate days for 14 weeks, reduced the tumor formation as well as protected the levels of cell surface glycoconjugates in DMBA painted hamsters. The present study thus suggests that TQ has potent chemopreventive efficacy as well as protected the abnormalities on cell surface glycoconjugates during DMBA induced hamster buccal pouch carcinogenesis. PMID- 21034529 TI - A novel method for predicting protein subcellular localization based on pseudo amino acid composition. AB - In this paper, a novel approach, ELM-PCA, is introduced for the first time to predict protein subcellular localization. Firstly, Protein Samples are represented by the pseudo amino acid composition (PseAAC). Secondly, the principal component analysis (PCA) is employed to extract essential features. Finally, the Elman Recurrent Neural Network (RNN) is used as a classifier to identify the protein sequences. The results demonstrate that the proposed approach is effective and practical. PMID- 21034530 TI - Dendritic localization and a cis-acting dendritic targeting element of Kv4.2 mRNA. AB - Kv4.2, a pore-forming alpha-subunit of voltage-gated A-type potassium channels, is expressed abundantly in the soma and dendrites of hippocampal neurons, and is responsible for somatodendritic I(A) current. Recent studies have suggested that changes in the surface levels of Kv4.2 potassium channels might be relevant to synaptic plasticity. Although the function and expression of Kv4.2 protein have been extensively studied, the dendritic localization of Kv4.2 mRNA is not well described. In this study, Kv4.2 mRNAs were shown to be localized in the dendrites near postsynaptic regions. The dendritic transport of Kv4.2 mRNAs were mediated by microtubule- based movement. The 500 nucleotides of specific regions within the 3'-untranslated region of Kv4.2 mRNA were found to be necessary and sufficient for its dendritic localization. Collectively, these results suggest that the dendritic localization of Kv4.2 mRNAs might regulate the dendritic surface level of Kv4.2 channels and synaptic plasticity. PMID- 21034531 TI - Protective effects of carnosine and homocarnosine on ferritin and hydrogen peroxide-mediated DNA damage. AB - Previous studies have shown that one of the primary causes of increased iron content in the brain may be the release of excess iron from intracellular iron storage molecules such as ferritin. Free iron generates ROS that cause oxidative cell damage. Carnosine and related compounds such as endogenous histidine dipetides have antioxidant activities. We have investigated the protective effects of carnosine and homocarnosine against oxidative damage of DNA induced by reaction of ferritin with H(2)O(2). The results show that carnosine and homocarnosine prevented ferritin/H(2)O(2)-mediated DNA strand breakage. These compounds effectively inhibited ferritin/H(2)O(2)-mediated hydroxyl radical generation and decreased the mutagenicity of DNA induced by the ferritin/H(2)O(2) reaction. Our results suggest that carnosine and related compounds might have antioxidant effects on DNA under pathophysiological conditions leading to degenerative damage such as neurodegenerative disorders. PMID- 21034532 TI - Preventable effect of L-threonate, an ascorbate metabolite, on androgen-driven balding via repression of dihydrotestosterone-induced dickkopf-1 expression in human hair dermal papilla cells. AB - In a previous study, we recently claimed that dihydrotestosterone (DHT)-inducible dickkopf-1 (DKK-1) expression is one of the key factors involved in androgen potentiated balding. We also demonstrated that L-ascorbic acid 2-phosphate (Asc 2 P) represses DHT-induced DKK-1 expression in cultured dermal papilla cells (DPCs). Here, we investigated whether or not L-threonate could attenuate DHT induced DKK-1 expression. We observed via RT-PCR analysis and enzyme-linked immunosorbent assay that DHT-induced DKK-1 expression was attenuated in the presence of L-threonate. We also found that DHT-induced activation of DKK-1 promoter activity was significantly repressed by L-threonate. Moreover, a co culture system featuring outer root sheath (ORS) keratinocytes and DPCs showed that DHT inhibited the growth of ORS cells, which was then significantly reversed by L-threonate. Collectively, these results indicate that L-threonate inhibited DKK-1 expression in DPCs and therefore is a good treatment for the prevention of androgen-driven balding. PMID- 21034533 TI - Three novel germline mutations in MLH1 and MSH2 in families with Lynch syndrome living on Jeju island, Korea. AB - Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant syndrome characterized by predisposition to early-onset cancers. HNPCC is caused by heterozygous loss-of-function mutations within the mismatch repair genes MLH1, MSH2, MSH6, PMS1, and PMS2. We genotyped the MLH1 and MSH2 genes in patients suffering from Lynch syndrome and in 11 unrelated patients who were diagnosed with colorectal cancer and had subsequently undergone surgery. Five Lynch syndrome patients carried germline mutations in MLH1 or MSH2. Two of these were identified as known mutations in MLH1: deletion of exon 10 and a point mutation (V384D). The remaining three patients exhibited novel mutations: a duplication (937_942dupGAAGTT) in MLH1; deletion of exons 8, 9, and 10; and a point mutation in MLH1 (F396I) combined with multiple missense mutations in MSH2 (D295G, K808E, Q855P, and I884T). The findings underline the importance of efficient pre screening of conspicuous cases. PMID- 21034534 TI - Susceptibility for breast cancer in young patients with short rare minisatellite alleles of BORIS. AB - In this study, we characterized two blocks of minisatellites in the 5' upstream region of the BORIS gene (BORIS-MS1, -MS2). BORIS-MS2 was found to be polymorphic; therefore, this locus could be useful as a marker for DNA fingerprinting. We assessed the association between BORIS-MS2 and breast cancer by a case-control study with 428 controls and 793 breast cancers cases. Rare alleles in the younger group (age, <40) were associated with a statistically significant increased risk of breast cancer (odds ratio, 4.84; 95% confidence interval, 1.06-22.22; and P = 0.026). A statistically significant association between the short rare alleles and cancer was identified in the younger group (8.02; 1.01-63.83; P = 0.021). Kaplan-Meier estimates showed that poor prognosis was associated with patients who contained the rare alleles. Our data suggest that the short rare alleles of BORIS-MS2 could be used to identify the risk for breast cancer in young patients. PMID- 21034535 TI - Swedish mutation within amyloid precursor protein modulates global gene expression towards the pathogenesis of Alzheimer's disease. AB - The Swedish mutation (K595N/M596L) of amyloid precursor protein (APP-swe) has been known to increase abnormal cleavage of cellular APP by Beta-secretase (BACE), which causes tau protein hyperphosphorylation and early-onset Alzheimer's disease (AD). Here, we analyzed the effect of APP-swe in global gene expression using deep transcriptome sequencing technique. We found 283 genes were down regulated and 348 genes were up-regulated in APP-swe expressing H4-swe cells compared to H4 wild-type cells from a total of approximately 74 million reads of 38 base pairs from each transcriptome. Two independent mechanisms such as kinase and phosphatase signaling cascades leading hyperphosphorylation of tau protein were regulated by the expression of APP-swe. Expressions of catalytic subunit as well as several regulatory subunits of protein phosphatases 2A were decreased. In contrast, expressions of tau-phosphorylating glycogen synthase kinase 3beta (GSK 3beta), cyclin dependent kinase 5 (CDK5), and cAMP-dependent protein kinase A (PKA) catalytic subunit were increased. Moreover, the expression of AD-related Aquaporin 1 and presenilin 2 expression was regulated by APP-swe. Taken together, we propose that the expression of APP-swe modulates global gene expression directed to AD pathogenesis. PMID- 21034536 TI - Cardiac resynchronization therapy for chronic heart failure in China: guideline and practice. PMID- 21034537 TI - Potential proarrhythmic effect of cardiac resynchronization therapy during perioperative period: data from a single cardiac center. AB - BACKGROUND: Cardiac resynchronization therapy (CRT) could improve heart function, symptom status, quality of life and reduce hospitalization and mortality in patients with severe heart failure (HF) with optimal medical management. However, the possible adverse effects of CRT are often ignored by clinicians. METHOD: A retrospective analysis of CRT over a 6-year period was made in a single cardiac center. RESULTS: Fifty-four patients were treated with CRT(D) device, aged (57 +/ 11) years, with left ventricular ejection fraction of (32.1 +/- 9.8)%, of which 4 (7%) developed ventricular tachycardia/ventricular fibrillation (VT/VF) or junctional tachycardia after operation. Except for one with frequent ventricular premature beat before operation, the others had no previous history of ventricular arrhythmia. Of the 4 patients, 3 had dilated cardiomyopathy and 1 had ischemic cardiomyopathy, and tachycardia occurred within 3 days after operation. Sustained, refractory VT and subsequent VF occurred in one patient, frequent nonsustained VT in two patients and nonparoxysmal atrioventricular junctional tachycardia in one patient. VT was managed by amiodarone in two patients, amiodarone together with beta-blocker in one patient, and junctional tachycardia was terminated by overdrive pacing. During over 12-month follow-up, except for one patient's death due to refractory heart and respiratory failure in hospital, the others remain alive and arrhythmia-free. CONCLUSIONS: New-onset VT/VF or junctional tachycardia may occur in a minority of patients with or without prior history of tachycardia after biventricular pacing. Arrhythmia can be managed by conventional therapy, but may require temporary discontinuation of pacing. More observational studies should be performed to determine the potential proarrhythmic effect of CRT. PMID- 21034538 TI - Beta2-adrenoceptor gene variant Arg16Gly is associated with idiopathic ventricular outflow-tract tachycardia. AB - BACKGROUND: Imbalance of the sympathetic nervous system was involved in the pathogenesis of idiopathic ventricular outflow-tract tachycardia (IVOT). We aimed to investigate whether the major genetic variants in beta(1)- and beta(2) adrenoceptors and GNB3 C825T were associated with IVOT and verapamil sensitive idiopathic left ventricular tachycardia (ILVT). METHODS: Patients with IVOT and ILVT from December 2005 to December 2007 were consecutively enrolled into this study. Controls were randomly selected from the community-based inhabitants. Five genetic variants, Ser49Gly and Gly389Arg in the beta(1)-adrenoceptor, Arg16Gly and Gln27Glu in the beta(2)-adrenoceptor and GNB3 C825T, were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS: A total of 227 patients with IVOT and 110 patients with ILVT were included. Genotyping revealed that the 16Gly allele of Arg16Gly variant of beta(2)-adrenoceptor was associated with a higher risk of IVOT (OR: 1.40, 95%CI: 1.12 - 1.75, P = 0.003 in the addictive model and OR: 1.62, 95%CI: 1.14 - 2.31, P = 0.007 in the dominant model). Patients with Gly16Gln27 haplotype also had a higher risk of IVOT (OR: 1.38, 95%CI: 1.11 - 1.73, P = 0.012). Other four variants, including Ser49Gly and Arg389Gly in beta(1)-adrenoceptor, Gln27Glu in beta(2)-adrenoceptor and GNB3 C825T, did not differ between patients with IVOT and controls. In patients with ILVT, no significant difference was found in these five variants compared with controls. CONCLUSIONS: Arg16Gly in beta(2) adrenoceptor is significantly associated with IVOT in Chinese Han population. Major genetic variants in beta(1)- and beta(2)-adrenoceptor and GNB3 C825T may not be associated with ILVT. These data suggest a different arrhythmogenic mechanism in IVOT and ILVT. PMID- 21034539 TI - Heart rate profile during exercise in patients with early repolarization. AB - BACKGROUND: Both early repolarization and altered heart rate profile are associated with sudden death. In this study, we aimed to demonstrate an association between early repolarization and heart rate profile during exercise. METHODS: A total of 84 subjects were included in the study. Comparable 44 subjects with early repolarization and 40 subjects with normal electrocardiogram underwent exercise stress testing. Resting heart rate, maximum heart rate, heart rate increment and decrement were analyzed. RESULTS: Both groups were comparable for baseline characteristics including resting heart rate. Maximum heart rate, heart rate increment and heart rate decrement of the subjects in early repolarization group had significantly decreased maximum heart rate, heart rate increment and heart rate decrement compared to control group (all P < 0.05). The lower heart rate increment (< 106 beats/min) and heart rate decrement (< 95 beats/min) were significantly associated with the presence of early repolarization. After adjustment for age and sex, the multiple-adjusted OR of the risk of presence of early repolarization was 2.98 (95%CI 1.21-7.34) (P = 0.018) and 7.73 (95%CI 2.84-21.03) (P < 0.001) for the lower heart rate increment and heart rate decrement compared to higher levels, respectively. CONCLUSIONS: Subjects with early repolarization have altered heart rate profile during exercise compared to control subjects. This can be related to sudden death. PMID- 21034540 TI - Gender specific association of neonatal characteristics and cardiovascular risk factors on carotid intima-media thickness in a Chinese cohort. AB - BACKGROUND: Multiple neonatal characteristics and adult cardiovascular risk factors are associated with the development of atherosclerosis, however little conclusive evidence exists characterizing the relative strength of these factors. In a large retrospective study, we investigated the association between both objective neonatal measurements and comprehensive adult cardiovascular risk factors with the development of atherosclerosis, quantified by carotid intima media thickness (CIMT). Further, we assessed the impact of gender on the relative impact of these risk factors. METHODS: CIMT, a measure of atherosclerosis, was determined by carotid ultrasound on 1568 participants (age 50-85) whose birth records were obtained from Peking Union Medical College Hospital. In addition, each participant was given a physical examination, and completed a medical questionnaire to identify a panel of cardiovascular risk factors. Multiple regression analysis was performed on the population and on the male and female cohorts individually, to identify the relative contribution of these risk factors to increased CIMT. RESULTS: For the total population the Framingham score, renal function, adult abdominal circumference and mother's gestational age were associated with CIMT, accounting for 14.7%, 1.4%, 0.9%, and 0.2% of total variance, respectively. In the male population the Framingham score, renal function, abdominal circumference and hemoglobin were the most significant risk factors for CIMT. Risk in the female population was associated with Framingham score, renal function, insulin resistance and gestational age. No relationship between birth weight or head circumference and CIMT were observed. CONCLUSIONS: Adult cardiovascular risk factors were the most significantly associated with the development of atherosclerosis; however mother's age at birth was associated with CIMT, particularly in the female cohort. The relative contribution of the risk factors analyzed varied between the male and female populations. PMID- 21034541 TI - Establishing 1H nuclear magnetic resonance based metabonomics fingerprinting profile for spinal cord injury: a pilot study. AB - BACKGROUND: Spinal cord injury (SCI) is a complex trauma that consists of multiple pathological mechanisms involving cytotoxic, oxidation stress and immune endocrine. This study aimed to establish plasma metabonomics fingerprinting atlas for SCI using (1)H nuclear magnetic resonance (NMR) based metabonomics methodology and principal component analysis techniques. METHODS: Nine Sprague Dawley (SD) male rats were randomly divided into SCI, normal and sham-operation control groups. Plasma samples were collected for (1)H NMR spectroscopy 3 days after operation. The NMR data were analyzed using principal component analysis technique with Matlab software. RESULTS: Metabonomics analysis was able to distinguish the three groups (SCI, normal control, sham-operation). The fingerprinting atlas indicated that, compared with those without SCI, the SCI group demonstrated the following characteristics with regard to second principal component: it is made up of fatty acids, myc-inositol, arginine, very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), triglyceride (TG), glucose, and 3-methyl-histamine. CONCLUSIONS: The data indicated that SCI results in several significant changes in plasma metabolism early on and that a metabonomics approach based on (1)H NMR spectroscopy can provide a metabolic profile comprising several metabolite classes and allow for relative quantification of such changes. The results also provided support for further development and application of metabonomics technologies for studying SCI and for the utilization of multivariate models for classifying the extent of trauma within an individual. PMID- 21034542 TI - Edge-to-edge chordal transfer repair for anterior leaflet prolapse of mitral valve in 21 patients. AB - BACKGROUND: Repair of anterior mitral leaflet (AML) prolapse is still a technical challenge for cardiac surgeons. It is an important issue to find a way to repair the AML prolapse with a reliable and reproducible technique. METHODS: Between January 2002 and June 2009, the operation of chordal transfer based on the "edge to-edge" technique was performed in 21 patients with serious mitral valve regurgitation because of prolapse of the anterior leaflet. After the operation, echocardiography was performed in each patient before discharge and at the time of follow-up. RESULTS: All patients survived the operation. One patient required mitral valve replacement because of anterior leaflet perforation 3 days after the operation. The other patients were free from reoperation. At the time of follow up, all these patients were in New York Heart Association (NYHA) functional class I. In all these patients, pre-discharge and follow-up echocardiography showed neither stenosis nor significant regurgitation of the mitral valve: the cross sectional area of the mitral valve was 3.3 - 4.8 cm(2) (mean (3.78 +/- 0.52) cm(2)), the mean regurgitation area was (0.45 +/- 0.22) cm(2). At the same time, both dimension of left atrium and left ventricle reduced significantly (left atrium diameter: pre-operation (48.26 +/- 11.12) mm, post-operation (37.57 +/- 9.56) mm, P < 0.05; the end-diastolic diameter of the left ventricle: pre operation (61.43 +/- 8.24) mm, post-operation (42.35 +/- 10.79) mm, P < 0.01). CONCLUSION: "Edge-to-edge" chordal transfer technique is a simple, reliable, and reproducible technique that can provide good results for repair of anterior leaflet prolapse of mitral valve. PMID- 21034543 TI - Pregnancy outcomes in women with heart disease. AB - BACKGROUND: As the Shanghai Obstetrical Cardiology Intensive Care Center, our hospital has accumulated a large number of clinical data of pregnant women with heart disease. This paper is a retrospective analysis of 1142 pregnancies in women with heart disease so as to evaluate the maternal and fetal outcomes of these patients. METHODS: A retrospective analysis was carried out for pregnancies in 1142 women with heart disease who delivered in Shanghai Obstetrical Cardiology Intensive Care Center between 1993 and 2007. RESULTS: In this study, main heart diseases in pregnancy were arrhythmia (n = 359, 31.4%), congenital heart disease (CHD; n = 291, 25.5%), and myocarditis and its sequelae (n = 284, 24.9%); based on the functional classification criteria of New York Heart Association (NYHA), more than half (n = 678, 59.4%) of patients were classified NYHA Class I; pregnant women in NHYA Class I-II (n = 951, 83.3%) commonly had arrhythmia, myocarditis and its sequelae, while those in NHYA Class III-IV (n = 191, 16.7%) mainly had CHD, rheumatic heart disease (RHD), cardiopathy induced by hypertensive disorders complicating pregnancy, and peripartum cardiomyopathy (PPCM). Cardiac failure occurred in 97 (8.5%) patients, and 8 (0.7%) maternal deaths and 12 (1.1%) perinatal deaths were reported in this study. Compared with those in NHYA Class I-II, women in NHYA Class III-IV had a significantly lower gestational age at birth (P < 0.05), lower birth weight (P < 0.01), and higher incidence of preterm delivery, small for gestational age and perinatal death (P < 0.01). The incidence of cardiac failure in pregnant women with cardiopathy induced by hypertensive disorders complicating pregnancy and PPCM was relatively high, with a rate of 80% and 52.2%, respectively. After cardiac operation, 131 (90.3%) women were in classified NHYA Class I-II and 14 (9.7%) in NHYA Class III IV. CONCLUSIONS: Arrhythmia is the type of heart disease that has a highest incidence in patients with heart disease in pregnancy, while main types of heart disease that impair cardiac function are CHD and RHD; cardiac failure is more frequently caused by cardiopathy induced by hypertensive disorders complicating pregnancy and PPCM; impaired cardiac function increases perinatal morbidity; cardiac surgery before pregnancy could improve the cardiac function. PMID- 21034544 TI - Relationships among hope, coping style and social support for breast cancer patients. AB - BACKGROUND: Breast cancer is one of the most common cancers in women, and its incidence seems to have gradually increased every year. During the treatment of breast cancer, patients suffer psychological morbidity, and hope is one important factor in maintaining psychological health. Therefore, in this study, we investigated the level of hope in Chinese women with breast cancer during chemotherapy and confirmed the relationships among hope, coping style, and social support. METHODS: One hundred and fifty-nine inpatients with breast cancer who were undergoing chemotherapy in two affiliated hospitals of Harbin Medical University were recruited and investigated. Each patient completed the Herth Hope Index (HHI), Jalowiec Coping Scale (JCS), and the social support scale made by XIAO Shui-yuan, and provided general demographic data. RESULTS: The mean hope level of the 159 patients with breast cancer was 38.62 +/- 4.56. There was a statistical difference between the hope level and monthly income. Analysis of results from the Pearson test showed no relationship between the hope level and coping style; however, there were positive relationships between hope and optimism, hope and self-reliance, and hope and palliative coping styles. In contrast, negative relationships were found between hope and the fatalistic and emotional coping styles. The total score of hope and social support had significantly positive relationship for the three scales. CONCLUSIONS: Patients with breast cancer achieved high levels of hope, with the level of hope being proportional to increase in the income. During chemotherapy, patients with breast cancer had adopted many coping styles. PMID- 21034545 TI - A comparison between vital capacity induction and tidal breathing induction techniques for the induction of anesthesia and compound A production. AB - BACKGROUND: Vital capacity induction and tidal breathing induction are currently administered for inhalation induction of anesthesia with sevoflurane. The aim of this study was to compare them using sevoflurane with respect to induction time, complications of inhalation induction, and compound A production in adult patients. METHODS: Fifty-one women with American Society of Anesthesiologists physical status I-II undergoing mammary gland tumorectomy were randomly assigned to receive either vital capacity induction or tidal breathing induction with 8% sevoflurane at 6 L/min followed by laryngeal mask airway insertion. Induction times, complications of inhalation induction, and vital signs were recorded. Inspired concentrations of compound A were assayed and sofnolime temperatures were monitored at one-minute intervals after sevoflurane administration. RESULTS: The time to loss of eyelash reflex was significantly shorter with the vital capacity induction technique than with the tidal breathing induction technique ((43.8 +/- 13.4) seconds vs. (70.8 +/- 16.4) seconds, respectively; P < 0.01). Cardiovascular stability was similar in both groups. The incidence of complications was significantly less with the vital capacity induction technique than with the tidal breathing induction technique (7.7% vs. 32%, respectively; P < 0.01). However, the mean and maximum concentrations of compound A during induction were significantly higher in the vital capacity group than those in the tidal breathing group (P < 0.05); compound A concentration at the beginning of anesthesia maintenance was (40.73 +/- 10.83) ppm in the vital capacity group and (29.45 +/- 7.51) ppm in tidal breathing group (P = 0.019). CONCLUSION: For inhalation induction of anesthesia, the vital capacity induction was faster and produced fewer complications than that for tidal breathing induction, but increased compound A production in the circuit system. PMID- 21034546 TI - Linkage of three polymorphisms on chromosome 20p12 to ossification of the posterior longitudinal ligament of spine and its severity in Han Chinese patients. AB - BACKGROUND: Ossification of the posterior longitudinal ligament (OPLL) is characterized by the replacement of ligamentous tissue with new ectopic bone formation, and has a strong genetic background. Because of the abnormal bone metabolic features and the strong genetic component, osteoporosis is a related disorder with OPLL. Three polymorphisms on chromosome 20p12 were identified associated with the risk of osteoporosis and osteoporotic fracture. The rs996544 (C/T) "TT" and rs965291 (G/A) "AA" genotypes conferred higher risks for vertebral and hip fractures. The osteoporosis haplotype is defined by two polymorphisms, rs1116867 (A) and D35548 (T). However, it remains unknown whether these three polymorphisms predispose to an increased frequency and severity of OPLL in Han Chinese patients. METHODS: A total of 420 OPLL patients and 506 age- and sex matched controls were studied. Three single nucleotide polymorphisms (SNPs), rs996544 (C/T), rs965291 (G/A) and rs1116867 (A/G), were analyzed by direct sequencing. Associations between these SNPs with the occurrence and extent of OPLL were statistically evaluated. RESULTS: There was no significant association between the rs996544 (C/T) polymorphism and the prevalence of OPLL. The rs1116867 (A/G) polymorphism "AG" genotype was associated with the occurrence of OPLL. The rs1116867 (A/G) polymorphism "G" allele was associated with the occurrence of OPLL, but not with the extent of OPLL. The rs965291 (G/A) polymorphism in female patients was statistically different between cases and controls (P < 0.05). The rs965291 (G/A) polymorphism "A" allele was associated with the occurrence of OPLL in female patients. For the rs965291 (G/A) polymorphism, patients with the "A" allele (genotype, "AG" or "AA") showed a significantly greater number of ossified cervical vertebrae than those without the "A" allele (genotype, "GG", P < 0.05), particularly in female patients. CONCLUSIONS: The rs1116867 (A/G) and rs965291 (G/A) polymorphisms on chromosome 20p12 are associated with the occurrence and the extent of OPLL, at least in Han Chinese subjects. Our data should advance our understanding of the molecular etiology of OPLL and may guide approaches to prevent the onset of OPLL. PMID- 21034547 TI - Chinese female breast cancer patients show a better overall survival than their male counterparts. AB - BACKGROUND: It is not clear if there is a difference in prognosis between male breast cancer (MBC) and female breast cancer (FBC) patients. The aim of this study was to compare the prognosis of MBC and FBC patients in China and the prognosis of MBC and their corresponding postmenopausal FBC patients. METHODS: Thirty-five MBC patients who were treated at the Sun Yat-sen University Cancer Center between 1969 and 2004 were enrolled in the study. Seventy FBC patients who were matched with the MBC patients for TNM stage, year of diagnosis, and age at diagnosis were simultaneously enrolled in the study. A second group comprising 18 MBC patients and their corresponding 36 matched postmenopausal FBC patients were also enrolled. The whole group and the postmenopausal groups were compared for five- and ten-year survivals. RESULTS: All the factors that could potentially affect prognosis were comparable among the groups except more FBC than MBC patients underwent endocrine therapy and a modified radical mastectomy. The 5- and 10-year survivals in the whole group were 81.6% and 60.3% for men and 90.7% and 73.5% for women (P = 0.02). The 5- and 10-year survival in the postmenopausal group was 82.5% and 100% for men and 66.0% and 85.9% for women (P = 0.159). CONCLUSIONS: Chinese FBC patients had a better prognosis than Chinese MBC patients. However, MBC patients and their corresponding postmenopausal FBC patients had a similar prognosis. PMID- 21034548 TI - Could tumor characteristics identified by colonoscopy predict the locally advanced rectal carcinoma? AB - BACKGROUND: Neoadjuvant chemoradiation is now considered the standard care for locally advanced rectal carcinoma (T3-4 or/and N1-2 lesions), but the accuracy of staging examinations including endorectal ultrasonography (ERUS) and MRI is far from excellent. In addition, the above staging equipment or professionals who perform the examinations may not be available in some hospitals, while preoperative colonoscopy and biopsy are usually obtainable in most hospitals. The objective of the present study was to investigate the clinical and pathological characteristics of locally advanced rectal carcinoma and identify candidates for neoadjuvant chemoradiation. METHODS: This was a retrospective study. Patients who were treated for rectal cancer at Changhai Hospital from January 1999 to July 2008 were identified from our prospectively collected database. Statistical analysis was performed using SPSS Software System (version 15.0). The Mann Whitney test, chi-square test and multivariate Logistic regression analysis were performed. RESULTS: A total of 1005 cases were included in this research, of which 761 cases were identified as locally advanced rectal carcinoma depending on postoperative TNM staging. The results of multivariate Logistic regression analysis indicated seven independent risk factors that could be used to predict a locally advanced rectal carcinoma independently: a high grade (including poor differentiation and undifferentiation) (OR: 3.856; 95% CI: 2.064 to 7.204; P = 0.000); large tumor size (OR: 2.455; 95% CI: 1.755 to 3.436; P = 0.000); elevated preoperative serum CEA level (OR: 1.823; 95% CI: 1.309 to 2.537; P = 0.000); non polypoid tumor type (OR: 1.758; 95% CI: 1.273 to 2.427; P = 0.001); the absence of synchronous polyps (OR: 1.602; 95% CI: 1.103 to 2.327; P = 0.013); the absence of blood in stool (OR: 1.659; 95% CI: 1.049 to 2.624; P = 0.030); and a greater circumferential tumor extent (OR: 1.813; 95% CI: 1.055 to 3.113; P = 0.031). Based on these findings, a Logistic equation was established, the accuracy of which was 64% according to the information of the additional 50 cases. CONCLUSIONS: Some independent risk factors related with locally advanced rectal carcinoma were identified, based on which it is possible to establish a Logistic equation as a tool to predict candidates of neoadjuvant chemoradiation. Further research about optimization of the equation is warranted. PMID- 21034549 TI - PDK1 plays a critical role in regulating cardiac function in mice and human. AB - BACKGROUND: PDK1 is an essential protein kinase that plays a critical role in mammalian development. Mouse lacking PDK1 leads to multiple abnormalities and embryonic lethality at E9.5. To elucidate the role of PDK1 in the heart, we investigated the cardiac phenotype of mice that lack PDK1 in the heart in different growth periods and the alteration of PDK1 signaling in human failing heart. METHODS: We employed Cre/loxP system to generate PDK1(flox/flox): alpha MHC-Cre mice, which specifically deleted PDK1 in cardiac muscle at birth, and tamoxifen-inducible heart-specific PDK1 knockout mice (PDK1(flox/flox):MerCreMer mice), in which PDK1 was deleted in myocardium in response to the treatment with tamoxifen. Transmural myocardial tissues from human failing hearts and normal hearts were sampled from the left ventricular apex to analyze the activity of PDK1/Akt signaling pathways by Western blotting. RESULTS: PDK1(flox/flox): alpha MHC-Cre mice died of heart failure at 5 and 10 weeks old. PDK1(flox/flox) MerCreMer mice died of heart failure from 5 to 21 weeks after the initiation of tamoxifen treatment at 8 weeks old. We found that expression levels of PDK1 in human failing heart tissues were significantly decreased compared with control hearts. CONCLUSION: Our results suggest that PDK1 signaling network takes part in regulating cardiac viability and function in mice, and may be also involved in human heart failure disease. PMID- 21034550 TI - Trueness investigation of routine creatinine assays on nine homogeneous systems in Beijing demonstrates an encouraging outcome that meets clinical requirements. AB - BACKGROUND: Serum creatinine (Scr) measurement plays a key role in glomerular filtration rate estimation (eGFR), chronic kidney disease (CKD) diagnosis as well as CKD treatment. However, the test results of Scr from different laboratories vary significantly. In order to get comparable results, the European in vitro diagnostic (IVD) directive requires traceability to reference methods and materials. The purpose of this study was to verify the effect of traceability implementation by investigating the trueness of creatinine measurement on nine homogenous systems in Beijing. METHODS: Commutable frozen human serum reference material, National Institute of Standards & Technology (NIST) Standard Reference Material (SRM) 967, was used to verify the trueness of Scr measurement results from nine homogeneous analytical systems of seven companies which are the most widely used systems in Beijing's third-grade hospitals. The methods referred to the Jaffe's and Enzymatic methods. RESULTS: from nine routine measurement systems were assessed using two criteria: biological variability and Clinical Laboratory Improvement Amendments' 88 (CLIA' 88). We simulated a series of broken lines representing the limits of SD and bias that would produce a relative increase (or decrease) of 10% and 20% in the measurement error when estimating GFR (MEeGFR) using the isotope dilution mass spectrometry (IDMS)-traceable Modification of Diet in Renal Disease (MDRD) Study equation. RESULTS: of the College of American Pathologists (CAP) 2008-B LN24 Survey were compared with our investigation results. RESULTS: Compared with the total error criteria of biological variability, Ortho (traceable to IDMS) met the minimum acceptable criteria; Roche (Jaffe), Roche (Enzymatic), Shino and Daiichi met the desirable criteria at level I. At level II, Ortho (traceable to gas chromatography/isotope dilution mass spectrometry, GC/IDMS), Dade Behring and Beckman (traceable to rate Jaffe) met the minimum acceptable criteria; Roche (Enzymatic) met the optimum criteria. The other five systems met the desirable criteria. Compared with the second criterion, all the results met the requirement of CLIA' 88. Trueness evaluation showed: the MEeGFR of Dade Behring exceeded 10% while the MEeGFRs of Beckman (traceable to rate Jaffe), Beckman (traceable to IDMS) and Ortho (traceable to Jaffe/High Performance Liquid Chromatography) exceeded 20% at level I. At level II the MEeGFRs of Dade Behring, Ortho (traceable to GC/IDMS) and Beckman (traceable to rate Jaffe) exceeded 10%. None of the nine systems got a MEeGFR higher than 20%. The conclusions of NIST SRM 967 agreed with those of LN 24 except for the Beckman measurement system. CONCLUSIONS: Trueness investigation of routine creatinine assays on nine homogeneous systems demonstrates an encouraging outcome that meets clinical requirements. Among the nine homogeneous routine systems, Roche and Daiichi produce the most accurate results. The implementation of traceability is effective. PMID- 21034551 TI - Transurethral dividing vaporesection for the treatment of large volume benign prostatic hyperplasia using 2 micron continuous wave laser. AB - BACKGROUND: The safety and efficiency of transurethral laser resection of the prostate to treat benign prostatic hyperplasia have been verified. However, this method does still not manage large volume prostates efficiently. To tackle this problem, we have designed a method of "transurethral dividing vaporesection of prostate" using a 2 micron continuous wave laser. The aim of this study was to evaluate the safety and efficiency of this method in the management of large prostates (> 80 ml). METHODS: In this study, 45 cases of benign prostatic hyperplasia with a median prostatic volume of (123.7 +/- 26.7) ml (range, 80.2 159.8 ml) were treated by the same surgeon under epidural anesthesia. During the surgery, superapubic catheters were needed, and saline solution was used for irrigation. First, the prostate was divided longitudinally into several parts from the bladder neck to the prostatic apex, and then gradually incised transversely chip by chip. Intraoperative blood transfusion rate, postoperative complications, maximum urinary flow rate, International Prostate Symptom Score and quality of life scores were recorded for statistical analysis using SPSS 16.0 software. RESULTS: Intraoperatively, no transurethral resection syndrome was observed, and no blood transfusions were needed. The resected prostatic chips were easily flushed out of the bladder through the resectoscope sheath without the use of a morcellator. Median vaporesection time was (95.0 +/- 13.2) minutes (range, 75-120 minutes), and the median retrieved and removed prostatic tissue were (25.2 +/- 5.1) g (range, 15.5-34.7 g) and (75.4 +/- 16.4) g (range, 43.8 106.1 g), respectively. Median catheter time and hospital stay were (3.3 +/- 0.9) days (range, 3-5 days) and (4.8 +/- 1.8) days (range, 3-9 days), respectively. After a follow-up of 6 to 12 months, two patients had stress urinary incontinence and three had anterior urethral strictures. Satisfactory improvement was seen in maximum urinary flow rate, International Prostate Symptom Score and quality of life scores. CONCLUSIONS: This study showed that 2 micron laser vaporesection is a safe treatment for benign prostatic hyperplasia patients with large prostates, and the method of "dividing vaporesection" may help improve both surgical efficiency and patient outcomes. PMID- 21034552 TI - Relationship between Trp64Arg mutation in the beta3-adrenergic receptor gene and metabolic syndrome: a seven-year follow-up study. AB - BACKGROUND: It has been shown that the beta3-adrenergic receptor (beta3-AR) gene Trp64Arg mutation was closely related to obesity and insulin resistance, and may be related to the prevalence of metabolic syndrome (MS). The aim of this study was to investigate the relationship between the beta3-AR gene mutation and the prevalence of MS. METHODS: A seven-year follow-up study was initiated in 2000, with 496 samples of simplex obese subjects (body mass index >= 25 kg/m(2)) and 248 normal-weight subjects. According to the beta3-AR genotypes, the subjects were classified as Trp64 homozygote group and Arg64 carrier group and after 7 years the prevalence of MS was determined. RESULTS: According to the baseline profile, there were no significant differences in the adiposity, blood pressure, lipid profile, fasting plasma glucose and fasting insulin between Trp64 homozygote group and Arg64 carrier group either in obesity or normal-weight subjects. The results of follow-up study indicated that in obese men the prevalence rate of MS was much higher in Arg64 carrier group than that in Trp64 homozygote group (54.76% vs. 40.85%, P < 0.05), but there was no statistical difference in women of the above groups. The prevalence rate of MS in obese men of both Trp64 homozygote group and Arg64 carrier obese group were obviously higher than that in women of the above groups (40.85% vs. 18.27% and 54.76% vs 21.28%, all P < 0.005). Differences were not statistically significant in the prevalence of MS for normal weight Trp64 homozygote group and normal weight Arg64 carrier group, either between men, between women, or between men and women. Comparison of populations indicated that no matter with the beta3-AR gene mutation or not, the prevalence of MS in obese subjects was significantly higher than normal weight subjects (chi(2) = 28.240 and chi(2) = 15.586, all P < 0.005). Logistic analysis showed that the mutation of beta3-AR gene was associated with the prevalence of MS in men. CONCLUSION: The mutation of beta3-AR gene is the independent risk factor for the prevalence of MS in men. PMID- 21034553 TI - Feasibility of vertebral internal fixation using deer and sheep as animal models. AB - BACKGROUND: Studies on new vertebral internal fixations of animals are very important prior to clinical application. This study aimed to determine the feasibility of vertebral internal fixation on morphologic and biomechanical properties using deer and sheep as animal models and comparing to human data. METHODS: Thirty sets of fresh Sika deer lumbar, 30 sets of fresh sheep lumbar, and 20 sets of fresh lumbar from male cadavers were used. We examined the morphology of the centra and pedicles of the three groups, and determined the cancellous bone density and biomechanical properties in all groups. RESULTS: There were marked differences in all parameters measured between the different species. The sizes of the upper, middle, and lower transverse diameter were largest in the human, followed by the deer, then the sheep. The index of centrum transverse diameters and sagittal diameters were less than 0.8 (a triangle), and the deer was more similar to the human. The heights of the right vertebral pedicles and the anterior disc heights (IDH) were largest in the human, followed by the deer, then the sheep. The apparent density, elastic modulus, and ultimate load were largest in the sheep, followed by the deer, then the human. The range of motion (ROM) of functional lumbar units (FLUs) with a combined flexion extension moment was largest in the human, followed by the deer then the sheep. CONCLUSIONS: The deer lumbar is more similar to that of human in anatomical form and biomechanics than the sheep lumbar. As such, deer is more appropriate as an animal model for use in vertebral internal fixation studies. PMID- 21034554 TI - Rosiglitazone reduces fatty acid translocase and increases AMPK in skeletal muscle in aged rats: a possible mechanism to prevent high-fat-induced insulin resistance. AB - BACKGROUND: As an agonist of peroxisome proliferator-activated receptor-gamma (PPARgamma), rosiglitazone can prevent acute fatty acid-induced insulin resistance in rats, however, the precise mechanisms by which rosiglitazone alleviates insulin resistance induced by high-fat diet need to be further investigated. METHODS: Wistar rats aged 23-24 weeks were divided into three groups: (1) aged control group (OC), (2) high-fat diet (HF) group and (3) high fat diet plus rosiglitazone maleate tablets (HF + Rosi) treatment group (n = 20 in each group). Insulin sensitivity was evaluated by conscious hyperinsulinemic euglycemic clamp technique. mRNA levels of fatty acid translocase (FAT/CD36), AMP activated protein kinase alpha1 (AMPKalpha1), AMPKalpha2 and acetyl CoA carboxylase (ACC) of rat skeletal muscle were determined using real-time PCR, while muscle carnitine palmitoyltransferase-1 (CPT-1beta) was determined using semi-quantitative PCR. Protein expression levels of FAT/CD36, AMPK phosphorylation (reflecting AMPK activity), P-ACC (inversely related with ACC activity) and muscle CPT-1M in rat skeletal muscles were measured using Western blotting. RESULTS: Aged rats fed by diet rich in fat for more than 8 weeks led to significant increases of plasma lipids, skeletal muscle intramuscular triglyceride and long-chain fatty acyl-CoA (LCACoA) compared to aged rats fed by normal chow diet (OC) (P < 0.05), which might correlate with the lower (reduced by 42.4%) whole body insulin sensitivity in HF rats. FAT/CD36 protein concentrations and mRNA levels increased in untreated HF aged rats (P < 0.01) and high-fat diet induced a significant decrease in P-AMPK, P-ACC, CPT-1M protein concentrations and AMPKalpha2 and CPT-1beta mRNA levels in rat skeletal muscles (P < 0.05). No change in AMPKalpha1 mRNA levels was observed in the HF group. CONCLUSION: High-fat diet in aged rats results in a lipid accumulation and subsequent insulin resistance, while rosiglitazone can alleviate the insulin resistance by reducing fatty acid uptake as well as enhancing lipometabolism. PMID- 21034555 TI - Sleep-related hypoxemia aggravates systematic inflammation in emphysematous rats. AB - BACKGROUND: Sleep disturbance is common in patients with emphysema. This study aimed to develop a novel model of sleep-related hypoxemia (SRH) in emphysema (SRHIE) with rats, and to explore the inflammatory status of SRHIE in lung, liver, pancreas, carotid artery and whole blood. METHODS: Seventy-five male Wistar rats were assigned to 5 groups with 15 per group according to the exposure conditions. The protocols varied with the degree of hypoxia exposure and severity of pre-existing emphysema caused by cigarette smoke exposure: (1) SRH control (SRHCtrl) group, sham smoke exposure (smoke exposure, exposed to smoke of 15 cigarettes twice everyday, 16 weeks) and SRH exposure (12.5% O2, 3 hours, SRH exposure, divide total hypoxia time (1.5 hours or 3 hours) into 4 periods evenly (22.5 minutes or 45 minutes) and distribute these hypoxia periods evenly into physiological sleep time of rats identified by electroencephalogram, week 9 to week 16); (2) Emphysema control (ECtrl) group, smoke exposure and sham SRH exposure (21% O2, 3 hours); (3) Short SRH in emphysema (SRHShort) group, smoke exposure and short SRH exposure (12.5% O2, 1.5 hours); (4) Mild SRH in emphysema (SRHMild) group, smoke exposure and mild SRH exposure (15% O2, 3 hours); (5) Standard SRH in emphysema (SRHStand) group, smoke exposure and SRH exposure (12.5% O2, 3 hours). ECtrl, SRHShort, SRHMild and SRHStand groups were groups with emphysematous rats. Two days before the end of exposure, 5 rats in each group were randomly selected for arterial blood gas analysis. In the rest 10 rats in each group, we obtained blood samples and bronchoalveolar lavage fluid (BALF) for routine tests. We also obtained tissue blocks of lung, liver, pancreas, and right carotid artery for pathologic scoring and measurements of liver oxidative stress (measuring hepatic oxidative stress enzymes, superoxide dismutase (SOD) activity, catalase (CAT) activity and malondialdehyde (MDA) concentration). RESULTS: Emphysematous groups had higher mean linear intercept (MLI) and mean alveolar number (MAN) values than SRHCtrl group. MLI values in SRHStand group were the highest (all P < 0.05). O2Sat in SRHStand rats when SRH exposure was (83.45 +/- 1.76)%. Histological scores of lung, liver, pancreas and right carotid artery were higher in emphysematous groups than SRHCtrl group, and SRHStand group were the highest (all P < 0.05) (SOD and CAT values were lower and MDA values were higher in groups with emphysema than without and in SRHStand group than in ECtrl group (all P < 0.05)). MDA values were the highest in SRHStand group (all P < 0.05). Total cellular score in BALF and White blood cell (WBC) in whole blood were the highest in SRHStand group (all P < 0.05). Lymphocyte ratios were the highest in SRHStand group both in BALF and blood (all P < 0.05). Red blood cell (RBC) and hemoglobin in emphysematous groups were higher than that in SRHCtrl group, and SRHStand group were higher than ECtrl group (all P < 0.05). CONCLUSIONS: With a proper novo model of SRHIE with Wistar rats, we have demonstrated SRH may aggravate the degree of emphysematous changes, polycythemia, oxidative stress and systematic inflammation. SRH and emphysema may have a synergistic action in causing systematic damages, and lymphocyte may be playing a central role in this process. Longer duration and more severe extent of SRHIE exposure also seem to result in more serious systematic damages. The mechanisms of all these concerned processes remain to be studied. PMID- 21034556 TI - Effects and mechanisms of non-restrictive external stent for prevention of vein graft restenosis in a rabbit model. AB - BACKGROUND: Among various treatments preventing vein graft restenosis, external stent is receiving more and more attention. This study aimed to investigate the effect of non-restrictive external stent on the prevention of vein graft restenosis and the potential mechanisms of platelet-derived growth factor (PDGF) in the process of restenosis. METHODS: Thirty-six "New Zealand white rabbits" were randomly divided into two groups, stented group (group S) and control group (non-stented group, group NS). Each rabbit underwent a reversed autologous external jugular vein into common carotid artery bypass grafting. In group S, the vein grafts were surrounded by a non restrictive stent which was 6 mm in diameter (a kind of Dacron vascular prosthesis); and in group NS, there was no stent to support the vein grafts. The grafts were harvested at the first week (1W), second week (2W) and fourth week (4W) after surgery respectively. The dimensions (including the thickness and area of the intima and media, luminal area) were measured by computer-aided image analysis system, and the intimal hyperplasia ratio was defined as the percentage of the area enclosed by the internal elastic lamina occupied by the intima. RESULTS: At 1W, the difference of the thickness and area of the intima between groups S and NS was not significant (P > 0.05); at 2W and 4W, the thickness and area of the intima and the intimal hyperplasia ratio in group S were less significant than those in group NS (P < 0.05); from 1W to 4W, the thickness and area of the media in group S were smaller than those in group NS (P < 0.05). Immunocytochemistry staining of PDGF-B showed that the percentage of positive cells of intima in both two groups was peaked at 2W, and a significantly smaller percentage was detected in group S compared with that in group NS at 2W and 4W (P < 0.05); the percentage of PDGF-B positive cells of media in both two groups was also peaked at 2W, and that in group S was smaller than that in group NS from 1W to 4W (P < 0.05); and the percentage of PDGF-B positive cells of adventitia in group S was peaked at 4W, whereas the percentage of adventitia in group NS peaked at 2W, and the percentage of adventitia in group S was greater than in group NS at 4W (P < 0.05). CONCLUSIONS: Non-restrictive external stenting inhibits the hyperplasia of the intima and media of the vein grafts and reduces the thickness and area of the intima and media; Non restrictive external stenting inhibits the synthesis of PDGF and changes its distribution, and then inhibits the hyperplasia of the intima. PMID- 21034557 TI - Inflammation inhibitory effects of sirolimus and paclitaxel-eluting stents on interleukin-1beta-induced coronary artery in-stent restenosis in pigs. AB - BACKGROUND: Coronary artery in-stent restenosis (ISR) and late stent thrombosis remain as important complications of stenting. The inflammation reactions to sirolimus and paclitaxel-eluting stents were investigated in a swine stenosis model induced by interleukin (IL)-1beta. METHODS: Mini pigs (n = 12; 2-3 months old and weighing 25-30 kg) were subjected to thoracotomy. Segments (10 mm) of the mid left anterior descending coronary artery and left circumflex coronary artery were exposed and aseptically wrapped with a cotton mesh soaked with IL-1beta (5 ug). After 2 weeks, the animals were anesthetized and quantitative coronary arteriography (QCA) was performed. The stenosis sites were randomized into three groups for stent insertion: a sirolimus-eluting stent (SES) group (Firebird(TM), n = 7), a paclitaxel-eluting stent (PES) group (TAXUS(TM), n = 9), and a bare metal stent (BMS) group (YINYITM, Dalian Yinyi Biomaterials Development Co., Ltd, China, n = 8). The three different stents were randomly implanted into stenosis segments. Expression of monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-alpha), P-selectin and vascular cell adhesion molecule 1 (VCAM-1) was determined by reverse transcription-coupled polymerase chain reaction (RT-PCR). RESULTS: QCA showed severe stenosis in IL-1beta treated segments. The SES and PES groups showed lower 1-month angiographic late lumen loss (LLL) within the stent and the lesion compared with BMS (P < 0.05) by follow up QCA. The SES showed lower LLL than that of PES in reducing 1-month inflammation lesions in pigs by follow-up QCA ((0.15 +/- 0.06) mm vs. (0.33 +/- 0.01) mm, P < 0.0001). The neointimal hyperplasia areas in SES and PES showed lower than those of BMS (SES (11.6 +/- 1.7) mm(2), PES (27.2 +/- 1.6) mm(2) vs. BMS (76.2 +/- 1.3) mm(2), P < 0.0001). The mRNA expression of MCP-1 by RT-PCR in SES and PES showed lower than that of BMS at 30 days after stenting (SES 0.20 +/- 0.03, PES 0.48 +/- 0.49 vs. BMS 0.58 +/- 0.07, P < 0.05). Levels of VCAM-1 in SES were significantly lower than those of PES and BMS (SES 0.35 +/- 0.08 vs. PES 0.65 +/- 0.13, BMS 0.70 +/- 0.06, P < 0.05). Histochemical immunostaining of vessel walls showed lower inflammatory chemokine MCP-1 expression in the SES and PES groups compared with BMS. CONCLUSION: SESs were superior in reducing 1-month angiographic LLL in inflammation lesions in pigs, strongly suggesting that SESs can suppress inflammatory reactions in ISR at multiple points. PMID- 21034558 TI - Expression and localization of annexin A7 in the rat lithium-pilocarpine model of acquired epilepsy. AB - BACKGROUND: Annexin A7 (synexin, ANXA7) is a member of annexins, which plays an essential role in the regulation of calcium homeostasis. Considerable evidence shows that the pathogenetic mechanism of acquired epilepsy (AE) has been related to the imbalance of calcium homeostasis. The aim of this study was to investigate ANXA7 expression and cellular localization in the cortex and hippocampus in the rat lithium-pilocarpine model of AE. METHODS: Totally 81 adult healthy male Wistar rats were randomly divided into control group (n = 9) and experimental group (n = 72), the experimental group contained eight subgroups according to sacrifice time (n = 9) (6-hour, 24-hour, 48-hour, 72-hour, 7-day, 15-day, 1 month, and 2-month). In the experimental group, rats were intraperitoneally injected by lithium-pilocarpine to induce AE model. We examined the expression and localization of ANXA7 via immunohistochemistry, double-label immunofluorescence with the use of neuron specific enolase (NSE) antibody, glial fibrillary acidic protein (GFAP) antibody and propidium iodide (PI), respectively. The data of optical density value were analyzed by analysis of variance. RESULTS: ANXA7 expression increased significantly in the experimental groups especially in the acute period (6 hours, 24 hours, and 48 hours after the onset of seizure) using immunohistochemistry. Double-label immunofluorescence and confocal microscopy disclosed that ANXA7 localized in the neurons but not in astrocytes and did not localize in the nucleus, which were performed with anti NSE, anti-GFAP and PI respectively. CONCLUSION: ANXA7 may play a potential role in the pathogenetic mechanisms of the rat lithium-pilocarpine model of AE. PMID- 21034559 TI - Role and mechanism of uncoupling protein 2 on the fatty acid-induced dysfunction of pancreatic alpha cells in vitro. AB - BACKGROUND: Uncoupling protein (UCP) 2 is related to the dysfunction of beta cells induced by fatty acids. However, whether UCP2 has similar effects on alpha cell is still not clear. This study aimed to investigate the effects of UCP2 and its possible mechanisms in lipotoxicity-induced dysfunction of pancreatic alpha cells. METHODS: The alpha TC1-6 cells were used in this study to evaluate the effects of palmitate and/or UCP2 inhibit factors on the glucagon secretory function, glucagon content, the glucagon mRNA level and the nitrotyrosine level in the supernatant. Meantime, the expression levels of UCP2 and peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1 alpha) were measured by real-time reverse transcription polymerase chain reaction (RT-PCR) and Western blotting. Furthermore, the possible relationship between UCP2 and insulin signal transduction pathway was analyzed. RESULTS: Palmitate stimulated alpha cell glucagon secretion and the expression of UCP2 and PGC-1 alpha, which could be partially decreased by the inhibition of UCP2. Palmitate increased nitrotyrosine level and suppressed insulin signal transduction pathway in alpha cells. Inhibition of UCP2 influenced the effects of free fatty acid on alpha cells and may relate to glucagon secretion. CONCLUSION: UCP2 played an important role on alpha cell dysfunction induced by free fatty acid in vitro, which may be related to its effects on oxidative stress and insulin signal transduction pathway. PMID- 21034560 TI - Functional recovery following traumatic spinal cord injury mediated by a unique polymer scaffold seeded with neural stem cells and Schwann cells. AB - BACKGROUND: The most important objective of transplant studies in the injured spinal cord has been to provide a favorable environment for axonal growth. Moreover, the continuing discovery of new grafts is providing new potentially interesting transplant candidates. Our purpose was to observe the morphological and functional repair effects of the co-transplantation of neural stem cell (NSC), Schwann cells (SCs) and poly lactide-co-glycolide acid (PLGA) on the spinal cord injury of rats. METHODS: A scaffold of PLGA was fabricated. NSCs and SCs were cultured, with the NSCs labeled with 5-bromodeoxyuridine, and the complex of NSC/PLGA or NSC + SCs/PLGA were constructed. Thirty-six Wistar rats were randomly divided into three groups: group A (transplantation of PLGA), group B (transplantation of NSC/PLGA) and group C (transplantation of NSC + SCs/PLGA). The 3 mm length of the right hemicord was removed under the microscope in all rats. The PLGA or the complex of PLGA-cells were implanted into the injury site. Basso-Beattie-Bresnahan (BBB) locomotion scores, motor and somatosensory evoked potential of lower limbs were examined to learn the rehabilitation of sensory and motor function at 4 weeks, 8 weeks, 12 weeks and 24 weeks after injury. All the recovered spinal cord injury (SCI) tissues were observed with HE staining, immunohistochemistry, and transelectronmicroscopy to identify the survival, migration and differentiation of the transplanted cells and the regeneration of neural fibres at 4 weeks, 8 weeks, 12 weeks and 24 weeks after injury. RESULTS: (1) From 4 weeks to 24 weeks after injury, the BBB locomotion scores of cell transplanted groups were better than those of the non-cell-transplanted group, especially group C (P < 0.05). The amplitudes of the somatosensory evoked potential (SEP) and motor-evoked potential (MEP) were improved after injury in groups B and C, but the amplitude of SEP and MEP at 4 weeks was lower than that at 12 weeks and 24 weeks after injury. Compared with group B, the amplitude of SEP and MEP in group C was improved. The amplitude of SEP and MEP was not improved after injury in group A. (2) HE staining revealed the volume of the scaffold decreased and the number of cells in the scaffold increased. Newly-grown capillaries also could be seen. Immunohistochemistry staining showed the transplanted NSCs could survive and migrate until 24 weeks and they could differentiate into neurons and oligodendrocytes. The regenerated axons were observed in the scaffold-cell complex with transelectronmicroscopy. The above manifestations were more extensive in group C. CONCLUSIONS: The transplanted NSC can survive and migrate in the spinal cord of rats up to 24 weeks after injury, and they can differentiate into various neural cells. Co-transplantation of cells/PLGA can promote the functional recovery of the injured spinal cord. The effect of co-transplanting NSC + SCs/PLGA is better than transplanting NSC/PLGA alone. PMID- 21034561 TI - Thrombin promotes human lung fibroblasts to proliferate via NADPH oxidase/reactive oxygen species/extracellular regulated kinase signaling pathway. AB - BACKGROUND: Thrombin is a multifunctional serine protease that plays a crucial role in hemostasis following tissue injury. In addition to its procoagulation effect, thrombin is also a potent mesenchymal cell mitogen, therefore it plays important roles in the local proliferation of mesenchymal cells in the tissue repair process. Reactive oxygen species (ROS) can induce some human cells to proliferate at lower rates while at higher concentrations they promote cells to undergo apoptosis or necrosis. Accumulative evidence suggests that thrombin can induce some cells to produce ROS. Based on these observations, we provide a hypothesis that thrombin can stimulate human lung fibroblasts to produce ROS, which play an important role in human lung fibroblast proliferation. METHODS: ROS were detected in fibroblasts at 30 minutes and 60 minutes following thrombin (20 U/ml) exposure using flow cytometry. The ratio of reduced glutathione/oxidized glutathione (GSH/GSSG) was assayed in lung fibroblasts using a commercial kit following treatment with thrombin at different concentrations. NADPH oxidase and the extracellular regulated kinase1/2 (ERK1/2) signaling pathway were detected by Western blotting after thrombin stimulation to lung fibroblasts. RESULTS: Thrombin, at 20 U/ml, stimulated human lung fibroblasts (HLF) to generate ROS in a time dependent manner. The ratio of GSH/GSSG in fibroblasts treated with thrombin showed a significant decrease. NADPH oxidase was activated and the ERK1/2 signal pathway was involved in the proliferation process of fibroblasts treated with thrombin. CONCLUSION: The activation of NADPH oxidase by thrombin leads to the production of ROS, which promotes fibroblasts proliferation via activation of the ERK1/2 signaling pathway. PMID- 21034562 TI - Intracellular CMTM2 negatively regulates human immunodeficiency virus type-1 transcription through targeting the transcription factors AP-1 and CREB. AB - BACKGROUND: The CKLF-like MARVEL transmembrane domain-containing family (CMTM) is a novel family of proteins linking chemokines and TM4SF. Different members exhibit diverse biological functions. In this study, the effect of intracellular CMTM2 on regulating human immunodeficiency virus type-1 (HIV-1) transcription was evaluated. METHODS: The effects of CMTM2 on regulating full-length HIV-1 provirus and the HIV-1 long terminal repeat (LTR)-directed transcription were assessed by luciferase assay. Transcription factor assays, using the luciferase reporter plasmids of AP-1, CRE, and NF-kappaB were conducted to explore the signaling pathway(s) that may be regulated by CMTM2. The potential relationship between CMTM2 and the transcription factor AP-1 was further analyzed by Western blotting analyses to investigate the effect of CMTM2 on PMA-induced ERK1/2 phosphorylation. RESULTS: The results from the current study revealed that CMTM2 acts as a negative regulator of HIV-1 transcription. CMTM2 exerted a suppressive action on both full-length HIV-1 provirus and HIV-1 LTR-directed transcription. Transcription factor assays showed that CMTM2 selectively inhibited basal AP-1 and CREB activity. Co-expression of HIV-1 Tat, a potent AP-1 and CREB activator, can not reverse CMTM2-mediated AP-1 and CREB inhibition, suggesting a potent and specific effect of CMTM2 on negatively regulating these two signaling pathways. CONCLUSION: Intracellular CMTM2 can negatively regulate HIV-1 transcription, at least in part, by targeting the AP-1 and CREB pathways. Exploring the mechanisms further may lead to new ways to control HIV-1 replication. PMID- 21034564 TI - Cardiac ablation by transesophageal high intensity focused ultrasound. PMID- 21034563 TI - Higher concentration of CO2 and 37 degrees C stabilize the less virulent opaque cell of Candida albicans. AB - BACKGROUND: Candida albicans (C. albicans) strains can spontaneously switch at a very low frequency from white to opaque phase. The ability to switch reversibly between white and opaque phenotype and contributes to the pathogenicity of C. albicans. White and opaque switching can be induced by various environmental signals. Previous study showed that opaque cells switch en masse to white when transferred in vitro to 37 degrees C, the temperature of their animal host. The objective of the present study was to determine the effect of different concentration of carbon dioxide and temperature on white-opaque switching, and to determine the different anti-candida killing activity of white and opaque form by human monocyte-macrophage cell line THP-1. METHODS: White-opaque switching and opaque-white switching were assayed. Modified Lee's medium supplemented with phloxine B was used to detect white and opaque forms of C. albicans under 0.03% CO2 at 25 degrees C, 0.03% CO2 at 37 degrees C and 5% CO2 at 37 degrees C. Growth curve of C. albicans was monitored using OD value at 630 nm simultaneously. White and opaque forms of C. albicans and THP-1 cells were cocultured at ratio of 1:10. Colony serial dilutions were used to assay for intracellular candidacidal activity. MTT assay was used to measure the extracellular candidacidal activity. RESULTS: Phenotype switching was successfully induced in vitro in all three strains of C. albicans. When evaluating white to opaque switching, opaque colony proportion of all colonies was 0.572 +/- 0.087, 0.920 +/- 0.030 and 0.985 +/- 0.026 exposure of white cells to 0.03% CO2 at 25 degrees C, 0.03% CO2 at 37 degrees C and 5% CO2 at 37 degrees C. When evaluating opaque to white switching, opaque colony proportion of all colonies was 0.600 +/- 0.114, 0.983 +/- 0.003 and 0.998 +/- 0.003 exposure of white cells to 0.03% CO2 at 25 degrees C, 0.03% CO2 at 37 degrees C and 5% CO2 at 37 degrees C. No significant difference of white or opaque form growth rate was found among three conditions (P > 0.05). THP-1 mediated extracellular anti-candida activity in white form was (79.80 +/- 3.71)% and (56.28 +/- 19.12)% at different dilution ratio, which were significantly lower than that in opaque form (100%, P < 0.01). THP-1 mediated intracellular anti-candida activity in white form ((62.98 +/- 5.02)%) was significantly lower than that in opaque form ((87.07 +/- 1.80)%, P < 0.01). CONCLUSIONS: Our results showed that opaque form is more vulnerable and less virulent than that in white form. It suggested that higher concentration of CO2 and 37 degrees C in host niches stabilize the less virulent opaque cell of C. albicans, which might have implications for pathogenesis, commensalism and mating. PMID- 21034565 TI - Effect of endothelial progenitor cells in neovascularization and their application in tumor therapy. AB - OBJECTIVE: To review the effect of endothelial progenitor cells in neovascularization as well as their application to the therapy of tumors. DATA SOURCES: The data used in this review were mainly from PubMed for relevant English language articles published from 1997 to 2009. The search term was "endothelial progenitor cells". STUDY SELECTION: Articles regarding the role of endothelial progenitor cells in neovascularization and their application to the therapy of tumors were selected. RESULTS: Endothelial progenitor cells isolated from bone marrow, umbilical cord blood and peripheral blood can proliferate, mobilize and differentiate into mature endothelial cells. Experiments suggest endothelial progenitor cells take part in forming the tumor vascular through a variety of mechanisms related to vascular endothelial growth factor, matrix metalloproteinases, chemokine stromal cell-derived factor 1 and its receptor C-X C receptor-4, erythropoietin, Notch signal pathway and so on. Evidence demonstrates that the number and function change of endothelial progenitor cells in peripheral blood can be used as a biomarker of the response of cancer patients to anti-tumor therapy and predict the prognosis and recurrence. In addition, irradiation temporarily increased endothelial cells number and decreased the endothelial progenitor cell counts in animal models. Meanwhile, in preclinical experiments, therapeutic gene-modified endothelial progenitor cells have been approved to attenuate tumor growth and offer a novel strategy for cell therapy and gene therapy of cancer. CONCLUSIONS: Endothelial progenitor cells play a particular role in neovascularization and have attractively potential prognostic and therapeutic applications to malignant tumors. However, a series of problems, such as the definitive biomarkers of endothelial progenitor cells, their interrelationship with radiotherapy and their application in cell therapy and gene therapy of tumors, need further investigation. PMID- 21034566 TI - RhoA/Rho kinase: a novel therapeutic target in diabetic complications. AB - OBJECTIVE: To reveal the roles of Rho kinase (ROCK) in the mechanisms of complications in diabetes by reviewing the correlations between ROCK and related complications in diabetes. DATA SOURCES: The data used in the present article were mainly from PubMed with relevant English articles published from 1998 to 2010. The search terms were "ROCK" and "diabetes". STUDY SELECTION: Original articles including the roles of ROCK or its inhibitors in diabetic complications and review articles about the biological character of ROCK were selected. RESULTS: The activity and expression of ROCK were up-regulated in the models of type 1 or type 2 diabetes animals and the cultured cells with concentrations of high glucose, ROCK activation was associated with the development or progression of complications in diabetes. Inhibition of RhoA/ROCK pathway prevented or ameliorated the pathologic changes of diabetic complications, and ROCK has been regarded as a key target for treatment of these complications. CONCLUSION: RhoA/ROCK signaling plays important roles in the pathogenesis of long-term complications in diabetes and ROCK inhibitors are becoming a promising solution to treatments of complications in diabetes. PMID- 21034567 TI - Complete genome sequence analysis of hepatitis B virus in a multidrug-refractory patient. PMID- 21034568 TI - Febuxostat, a nonpurine selective inhibitor of xanthine oxidase: a promising medical therapy for chronic heart failure? PMID- 21034569 TI - Non-reproducible results in genetic association studies in chronic hepatitis B due to the inadequate controls. PMID- 21034570 TI - Catheter ablation of atrial fibrillation in a patient with dextrocardia: what is the challenge? PMID- 21034571 TI - A diagnosis neglected for 6 years: report of a misdiagnosed case of pulmonary mucormycosis and review of the literature. PMID- 21034572 TI - Pulmonary embolism due to the right atrial thrombus mimicking atrial myxoma. PMID- 21034573 TI - Development of cerebral venous sinus thrombosis in an aplastic anemia patient with antiphospholipid syndrome. PMID- 21034574 TI - Aspirin induced asthma accompanied with allergic bronchopulmonary aspergillosis: a case report. PMID- 21034575 TI - A new type of cardiac neoplasm: Evans tumor. PMID- 21034576 TI - Levels of main platelet thrombin receptors in older chronic haemodialysis patients. PMID- 21034577 TI - Development of neonatal respiratory support and intensive care in emerging regions of China. PMID- 21034578 TI - Strategies to prevent necrotising enterocolitis. PMID- 21034579 TI - Lipid infusion and intravenous access in newborn infants. PMID- 21034581 TI - Epidemiology of respiratory distress and the illness severity in late preterm or term infants: a prospective multi-center study. AB - BACKGROUND: The severity of respiratory distress was associated with neonatal prognosis. This study aimed to explore the clinical characteristics, therapeutic interventions and short-term outcomes of late preterm or term infants who required respiratory support, and compare the usage of different illness severity assessment tools. METHODS: Seven neonatal intensive care units in tertiary hospitals were recruited. From November 2008 to October 2009, neonates born at >= 34 weeks' gestational age, admitted at < 72 hours of age, requiring continuous positive airway pressure (CPAP) or mechanical ventilation for respiratory support were enrolled. Clinical data including demographic variables, underlying disease, complications, therapeutic interventions and short-term outcomes were collected. All infants were divided into three groups by Acute care of at-risk newborns (ACoRN) Respiratory Score < 5, 5 - 8, and > 8. RESULTS: During the study period, 503 newborn late preterm or term infants required respiratory support. The mean gestational age was (36.8 +/- 2.2) weeks, mean birth weight was (2734.5 +/- 603.5) g. The majority of the neonates were male (69.4%), late preterm (63.3%), delivered by cesarean section (74.8%), admitted in the first day of life (89.3%) and outborn (born at other hospitals, 76.9%). Of the cesarean section, 51.1% were performed electively. Infants in the severe group were more mature, had the highest rate of elective cesarean section, Apgar score < 7 at 5 minutes and resuscitated with intubation, the in-hospital mortality increased significantly. In total, 58.1% of the patients were supported with mechanical ventilation and 17.3% received high frequency oscillation. Adjunctive therapies were commonly needed. Higher rate of infants in severe group needed mechanical ventilation or high frequency oscillation, volume expansion, bicarbonate infusion or vasopressors therapy (P < 0.05). The incidence of complications was also increased significantly in severe group (P < 0.05). The in-hospital mortality in the severe group was significantly higher than other two groups (P < 0.05). ACoRN Respiratory Score was correlated with Score for Neonatal Acute Physiology-Version II (SNAP-II) (P < 0.01). High gestational age, high SNAP-II score and oxygenation index (OI), and Apgar score at 5 minutes < 5 were independent risks for death. CONCLUSIONS: Neonatal respiratory distress is still a common cause of hospitalization in China. Illness severity assessment is important for the management. ACoRN Respiratory Score which correlated with SNAP-II score is easy to use and may be helpful in facilitating the caregivers in local hospital to identify the early signs and make the transfer decision promptly. PMID- 21034580 TI - Current status of neonatal acute respiratory disorders: a one-year prospective survey from a Chinese neonatal network. AB - BACKGROUND: We conducted a prospective, multicenter investigation of incidence, management and outcome of neonatal acute respiratory disorders (NARD), and evaluated related perinatal risk factors and efficacy of respiratory therapies in neonatal intensive care units (NICUs) in a Chinese neonatal network. METHODS: Data were prospectively collected in 2004 - 2005 from infants with NARD defined as presence of respiratory distress and oxygen requirement during the first 3 days of life. RESULTS: A total of 2677 NARD was classified (20.5% of NICU admissions). There were 711 (5.44%) with respiratory distress syndrome (RDS), 589 (4.51%) pulmonary infection, 409 (3.13%) meconium aspiration syndrome, 658 (5.03%) aspiration of amniotic fluid and 239 (1.83%) transient tachypnoea. Meconium aspiration syndrome had the highest rate with fetal distress, transient tachypnoea from cesarean section, and RDS with maternal disorders. Assisted mechanical ventilation was applied in 53.4% of NARD, and in above five disorders with 84.7%, 52.3%, 39.8%, 24.5%, and 53.6%, respectively. Corresponding mortality in these disorders was 31.4%, 13.6%, 17.8%, 4.1% and 5.0%, respectively. Surfactant was provided to 33.9% of RDS. In all RDS infants, the survival rate was 78.8% if receiving surfactant, and 63.4% if not (P < 0.001). CONCLUSIONS: This study provided NICU admission-based incidence and mortality of NARD, reflecting efficiency of advanced respiratory therapies, which should be a reference for current development of respiratory support in NICU at provincial and sub-provincial levels, justifying efforts in upgrading standard of care in emerging regions through a collaborative manner. PMID- 21034582 TI - A 12-month prospective survey of perinatal outcome of liveborn neonates in Julu County, China. AB - BACKGROUND: Population based epidemiologic study on the main diseases and birth status of liveborn neonates remains scarce in China, especially in rural areas where a large number of neonates are born. The aim of this study was to establish an epidemiological basis of live births in Julu County, a representative of the northern and mid-western parts of China in terms of demography, disease pattern and women and children's health care infrastructure. METHODS: The perinatal data of all live births were prospectively collected in three participating county level hospitals from September 1, 2007 to August 30, 2008. RESULTS: There were 5822 live births in these hospitals. Among all live births, 53.7% were male and 4.5% were born prematurely. Mean (SD) birth weight (BW) was (3348 +/- 503) g. The low (< 2500 g) and very low BW (< 1500 g) infants accounted for 3.8% and 0.5% of the total births, with 6.5% as small for gestational age and 2.8% as multi births. Cesarean section rate was 30.2%, of which 68.6% were elective. There were 745 infants (12.8% of the live births) admitted to local neonatal wards within 7 days of postnatal life, in which 48.3% and 19.3% were due to perinatal asphyxia and prematurity, respectively. The incidences of perinatal aspiration syndrome, transient tachypnea and respiratory distress syndrome were 4.9%, 0.6% and 0.5%, respectively. Neonatal mortality was 7.60/00 (44/5822), with 16 in delivery room and 28 in neonatal ward before discharge. CONCLUSIONS: This study provided a population-based perinatal data of live births and neonatal mortality in a northern China county with limited resources. Neonatal disorders related to perinatal asphyxia remain a serious clinical problem, which calls for sustained education of advanced neonatal resuscitation and improvement in the quality of perinatal-neonatal care. PMID- 21034583 TI - IFN-gamma release assay: a diagnostic assistance tool of tuberculin skin test in pediatric tuberculosis in China. AB - BACKGROUND: Prompt diagnosis of Mycobacterium tuberculosis (MTB) infection is an essential step in tuberculosis control and elimination. However, it is often difficult to accurately diagnose pediatric tuberculosis (TB). The tuberculin test (TST) may have a low specificity because of cross-reactivity with antigens present in Mycobacterium bovis bacillus Calmette-Guerin (BCG) and other mycobacteria, especially in China with a predominantly BCG-vaccinated population. Early-secreted antigenic target 6-kDa protein (ESAT-6) and culture filtrate protein 10 (CFP-10), stand out as suitable antigens that induce an interferon gamma (IFN-gamma) secreting, T-cell-mediated immune response to infection. While, considered the higher costs and complexity of the IFN-gamma release assay (TSPOT), we aimed to evaluate the TSPOT and TST test in the clinical diagnosis of pediatric tuberculosis and to establish a diagnostic process suitable for China. METHODS: The sensitivity and specificity of the assay were evaluated in total seventy four children with active tuberculosis and fifty one nontuberculous children with other disease, and then the results were compared with TST. Logistic regression models were used to identify variables that were associated with positive results for each assay. The independent variables included sex, age, birth place, vaccination history, close contract with an active TB patient. RESULTS: The sensitivity of TSPOT was higher than TST in active TB children with or without BCG vaccination, as well as in children with culture-confirmed TB. But the difference was not significant statistically. Combining results of the TSPOT and TST improved the sensitivity to 94.6%. Agreement of the TST and TSPOT was low (77.0%, kappa = 0.203) in active TB patients. The difference in specificity between TSPOT and TST test was statistically significant (94.1% vs. 70.6%, P = 0.006). Specificity of the two tests in patients without prior BCG vaccination history was similar (80.0% vs. 60.0%). The concordance between the two tests results in BCG vaccinated subjects was low (71.7%, kappa = 0.063). For TSPOT, none of the included risk factors was significantly associated with positive results. For TST, BCG vaccination (OR: 1.78; 95%CI: 1.30 - 2.00) was significantly associated with positive results. CONCLUSIONS: Although IFN-gamma release assay had relatively high sensitivity and specificity, we also should consider the higher costs and complexity of this test. Therefore, TSPOT could be used as the complementary tool of TST in circumstances when a suspected patient with negative TST results, or to exclude a positive TST result caused by BCG vaccination. PMID- 21034584 TI - Body mass index correlated with forced expiratory volume in 1 second/forced vital capacity in a population with a relatively low prevalence of obesity. AB - BACKGROUND: Obesity is the most common metabolic disease in the world. However, the relationship between obesity and lung function is not fully understood. Although several longitudinal studies have shown that increases in body weight can lead to reductions in pulmonary function, whether this is the case with the Japanese population and whether high body mass index (BMI) status alone represents an appropriate predictor of obstructive lung dysfunction remains unclear. The purpose of present study was to estimate the effect of BMI on lung function measured by spirometry of Japanese patients in general clinics. We measured BMI and performed spirometry on screening patients who had consulted general clinics. METHODS: Subjects comprised 1231 patients >= 40 years of age (mean age (65.0 +/- 12.0) years, 525 men, 706 women) who had consulted clinics in Nagasaki Prefecture, Japan, for non-respiratory disease. BMI was calculated and lung function was measured by spirometry. RESULTS: BMI was found to be positively correlated with forced expiratory volume in 1 second (FEV(1))/forced vital capacity (FVC) in men and with maximum mid-expiratory flow (MMF) in all subjects. Following adjustment for relevant factors, a significant positive correlation between BMI and FEV(1)/FVC was identified for all subjects. Comparison between subjects with normal BMI (18.5 - 25.0) and higher BMI (25.1 - 30.0) also demonstrated that FEV(1)/FVC and percentage of predicted maximum mid-expiratory flow (%MMF) were significantly higher in the latter subjects. CONCLUSIONS: In a population without marked respiratory disease, higher BMI subjects showed less obstructive pulmonary dysfunction compared to normal BMI subjects. High BMI status alone may be inappropriate as a predictor of obstructive lung dysfunction, particularly in populations with a low prevalence of obesity. PMID- 21034585 TI - Clinical outcomes and cost-utility after sirolimus-eluting versus bare metal stent implantation. AB - BACKGROUND: Randomized studies have shown beneficial effects of drug-eluting stent (DES) in reducing the risk of repeated revascularization. Other studies have shown higher proportion of death, myocardial infarction (MI) and increased cost concerning DES. However the long term safety and effectiveness of DES have been questioned recently. METHODS: To compare long term clinical outcomes, health related quality of life (HRQOL) and cost-utility after sirolimus-eluting stent (SES) and bare metal stent (BMS) implantation in angina patients in China, 1241 patients undergoing percutaneous coronary revascularization (PCI) with either SES (n = 632) or BMS (n = 609) were enrolled continuously in this prospective, nonrandomized, multi-center registry study. RESULTS: Totally 1570 stents were implanted for 1334 lesions. Follow-up was completed in 1205 (97.1%) patients at 12 months. Rates of MI, all causes of death were similar between the two groups. Significant differences were found at rate of cardiovascular re-hospitalization (136 (22.4%) in BMS group vs. 68 (10.8%) in SES group, P = 0.001) and recurrent angina (149 (24.5%) vs. 71 (11.3%), P = 0.001). Dramatic difference was observed when compared the baseline and 9-month HRQOL scores intra-group (P < 0.001). However no significant difference was found inter-group either in baseline or follow-up HRQOL. Compared with SES, the total cost in BMS was significantly lower on discharge (62 546.0 vs. 78 245.0 Yuan, P = 0.001). And follow-up expenditure was remarkably higher in the BMS group than that in the SES group (13 412.0 vs. 8 812.0 Yuan, P = 0.0001). CONCLUSIONS: There were no significant differences on death, in-stent thrombosis, MI irrespective of stent type. SES was superior to BMS on improvement of life quality. SES was with higher cost-utility compared to BMS. PMID- 21034586 TI - Management of sternal osteomyelitis and mediastinal infection following median sternotomy. AB - BACKGROUND: Median sternotomy is considered the most usually performed procedure in cardiac operations. This study aimed to assess clinical effectiveness of bilateral pectoralis major muscle flaps (BPMMF) for management of sternal osteomyelitis and mediastinal infection following median sternotomy. METHODS: Clinical data were collected and retrospectively analyzed from twelve patients who underwent the BPMMF transposition for management of sternal osteomyelitis and mediastinal infection following median sternotomy from January 2006 to June 2009. Procedure consisted of rigorous debridement of necrotic tissues, dead space obliteration using the BPMMF, and placement of drainage tubes connected to a negative pressures generator for adequate drainage. RESULTS: No patients died of drainage, and all 12 patients had viable BPMMF when discharged from hospital. At 1 week post discharge, 2 patients presented with sternal infection but recovered following local debridement and medication. No patients showed infection recurrence during the follow-up period over 10 months. CONCLUSIONS: Sternal osteomyelitis and mediastinal infection following median sternotomy may be effectively managed through rigorous debridement of infected soft tissues, resection of the damaged sternal segment, transposition of the BPMMF to fill the damaged sternum resulting from debridement, and adequate postoperative drainage. PMID- 21034587 TI - Effect of cigarette smoking on clinical outcomes of hospitalized Chinese male smokers with acute myocardial infarction. AB - BACKGROUND: Smoking is known to be a strong risk factor for premature atherosclerosis, acute myocardial infarction (AMI) and sudden cardiac death. According to a cross-sectional survey conducted in 2000 - 2001 in China, the prevalence of smoking among the Chinese men was 60.2%, the highest prevalence in the world. Up to date, the relationship between smoking and AMI in Chinese male smokers is still unclear. This study analyzed the baseline characteristics for male smokers hospitalized with AMI and investigated the effect of cigarette smoking on their clinical outcomes. METHODS: A total of 890 men aged 18 years or over with AMI were prospectively recruited from 1 January 2007 to 31 December 2009 from Shanxi Provincial People's Hospital. Patients were grouped into smokers and nonsmokers. The relationships between baseline characteristics and clinical outcomes were tested using either the chi-square test for trend for discrete variables or analysis of variance for continuous variables. RESULTS: Smokers accounted for 66.7% (594), more than twice of nonsmokers (296 (33.3%)), and were averaged 7 years younger ((56.61 +/- 11.44) vs. (63.61 +/- 11.62) years, P < 0.001). Smokers had the higher rate of TIMI flow grade 2 or 3 after thrombolytic therapy (42.4% vs. 24.5%, P = 0.002), 1 vessel disease (25.5% vs. 14.5%, P = 0.003) than nonsmokers. Smokers had better in-hospital outcome with lower in hospital mortality rate than nonsmokers (6.2% vs. 10.8%, P = 0.023). CONCLUSIONS: Male smokers suffered from AMI in this study presented an average of 7 years earlier than nonsmokers and were more than twice as likely to have AMI as nonsmokers in China. Smoking appeared to result in earlier infarction, especially ST elevated myocardial infarction in otherwise healthier patients who are likely to survive. PMID- 21034588 TI - Diagnostic value of contrast-enhanced intraoperative Doppler sonography for cerebral arteriovenous malformations compared with angiography. AB - BACKGROUND: Intraoperative Doppler sonography has been used in the neurosurgical operating room for the localization and description of cerebral arteriovenous malformations (AVMs). This study aimed to investigate the clinical value of contrast-enhanced intraoperative Doppler sonography, including its ability to assess the location and identify of feeding arteries in patients with AVMs and to compare this method with angiography. METHODS: Twenty-three patients with cerebral AVMs who were diagnosed using angiography, were examined with contrast enhanced intraoperative Doppler sonography. As an echo-enhancing agent, Sulphur Hexafluoride Microbubbles for Injection ("SonoVue") was administered intravenously in all patients. Sonogram results were reviewed and correlated with angiographic findings. For statistical analysis, the Wilcoxon signed-rank test was applied. RESULTS: Angiography identified 20 AVM lesions in the anterior or middle fossa and 3 in the posterior fossa. Contrast-enhanced intraoperative Doppler was somewhat less sensitive for only detecting 21/23 (91.3%) of the AVM lesions. Additionally, contrast-enhanced intraoperative Doppler slightly underestimated AVM size compared with angiographic findings but showed feeding arteries with sufficient acoustic properties. In 15 patients, angiography revealed a coincidental blood supply from another intracranial vessel, which was missed by contrast-enhanced intraoperative Doppler sonography. CONCLUSIONS: In a limited group of patients with AVMs, contrast-enhanced intraoperative Doppler sonography was a less sensitive but useful and simple method for the detection of AVMs in contrast to angiography. No specific untoward effects were attributed to the use of "SonoVue" as a contrast-enhancing substance. PMID- 21034589 TI - Significance of the preoperative guidance of dual-source CT in carotid body tumor. AB - BACKGROUND: Accurate views of the head and neck vessels, tumor angiogenesis and the relationship of tumor and the surrounding blood vessels are especially crucial to carotid body tumor (CBT) patients. The aim of this study was to explore the value of dual-source CT (DSCT) cerebral and carotid angiography in CBT diagnosis. METHODS: DSCT cerebral and carotid angiography was performed on nine patients with CBT. Two-dimensional and three-dimensional reconstruction images were obtained by means of multiple planar reconstructions (MPR), maximum intensity projection (MIP) and volume rendering (VR). All patients were subjected to color Doppler flow imaging (CDFI) examination. Two kinds of examinations were performed in 3 days, and all patients were confirmed by surgery. RESULTS: DSCT angiography was successful in all patients. CBTs were diagnosed in 9 patients with 10 lesions (1 case had multiple bilateral CBTs). The largest lesion was 12 cm in diameter, and the smallest one was 1.6 cm in diameter. All patients had clearly demonstrated head and neck vessels, tumor angiogenesis, and tumor relationship with the surrounding blood vessels. The internal and external carotid artery (ICA, ECA) were involved in 2 cases. There were 7 cases with basilar artery ring integrity, and 1 case had the posterior communicating artery absent; 1 case had middle cerebral artery stenosis; 4 cases (4 tumors) showed arterial phase homogeneous enhancement; 5 cases (6 tumors) had obvious heterogeneous enhancement where irregular low-density necrosis could be seen in the tumors. CDFI could demonstrate the nearby blood vessels and tumor structure, instead of tumor angiogenesis. However, DSCT can display both the tumor and the peripheral vascular tumor angiogenesis consistent with surgical findings. CONCLUSIONS: DSCT cerebral and carotid angiography can provide reliable information for the operation. It might be a valuable CBT diagnostic method by showing accurate views of the CBT along with the bilateral neck and brain blood vessels. PMID- 21034590 TI - Differential diagnosis of metastasis from non-metastatic lymph nodes in cervical cancers: pilot study of diffusion weighted imaging with background suppression at 3T magnetic resonance. AB - BACKGROUND: Diffusion weighted imaging with background suppression (DWIBS) is potentially useful in detecting metastatic lymph nodes. This study aimed to evaluate the efficacy of DWIBS at 3T magnetic resonance (MR) for diagnosing metastatic lymph nodes in cervical cancer. METHODS: This retrospective study included 25 patients with cervical cancer who underwent MR examination and were treated by hysterectomy and lymphadenectomy. The metastatic and non-metastatic lymph nodes were histologically proven by operation. Apparent diffusion coefficient (ADC) values, long-axis diameters, short-axis diameters, ratio of short- to long-axis diameters of all the identifiable lymph nodes were measured and compared. RESULTS: Twenty-five primary tumor lesions, 17 metastatic lymph nodes and 140 non-metastatic lymph nodes were pathologically confirmed in 25 cases with cervical cancer. The difference of ADC values between primary tumor lesions, metastatic and non-metastatic lymph nodes were statistically significant (F = 7.93, P = 0.001). There was no statistically significant difference between primary tumor lesions of cervical cancer and metastatic lymph nodes (t = -0.75, P = 0.456), and the difference between primary tumor lesions and non-metastatic lymph nodes was statistically significant (t = 4.68, P < 0.001). The ADC values, long-axis diameters, short-axis diameters, ratio of short- to long-axis diameters of metastatic and non-metastatic lymph nodes were (0.86 +/- 0.36) * 10(-3) mm(2)/s vs. (1.12 +/- 0.34) * 10(-3) mm(2)/s, (1.51 +/- 0.41) cm vs. (1.19 +/- 0.36) cm, (1.16 +/- 0.35) cm vs. (0.77 +/- 0.22) cm, 0.78 +/- 0.17 vs. 0.68 +/- 0.19 respectively, and statistically significant difference existed between two groups. CONCLUSIONS: DWIBS at 3T MR has the distinct advantages in detecting pelvic lymph nodes of cervical cancer. Quantitative measurement of ADC values could reflect the degree of restriction of diffusion of metastatic and non metastatic lymph nodes. The combination of size and ADC value would be useful in the accurate diagnosis of metastatic lymph nodes. PMID- 21034591 TI - Modified partially wide tangents technique in post-mastectomy radiotherapy for patients with left-sided breast cancer. AB - BACKGROUND: The role of internal mammary nodes (IMN) irradiation for breast cancer patients after mastectomy remains controversial. This study aimed to compare different techniques for radiation of the chest wall (CW) and IMN post mastectomy for left-breast cancer patients in terms of dose homogeneity within planning target volume (PTV) and dose to critical structures. METHODS: Thirty patients underwent CT simulation, while CW, IMN, left lung, heart and contralateral breast were contoured. Three three-dimensional conformal radiotherapy (3D-CRT) techniques, namely, standard tangents, partially wide tangents (PWT), and modified PWT techniques plus intensity modulated radiotherapy (IMRT) technique have been used to radiate CW and IMN. In addition to the target coverage and dose homogeneity, we also evaluated the dose to the critical structures including heart, left lung and contralateral breast. RESULTS: All three 3D-CRT techniques provided satisfactory coverage regarding total PTV. The PWT and the modified PWT gave better coverage of IMN PTV with V(47.5) of (96.83 +/- 4.56)% and (95.19 +/- 3.90)% compared to standard tangents ((88.16 +/- 7.77)%), P < 0.05. The standard tangents also contributed the biggest IMN V(D105%), V(D110%), V(D115%) and V(D120%). The lowest mean dose of the heart was achieved by the modified PWT ((8.47 +/- 2.30) Gy), compared with PWT ((11.97 +/- 3.54) Gy) and standard tangents ((11.18 +/- 2.53) Gy). The mean dose of lung and contralateral breast with the modified PWT was significantly lower than those with PWT. Comparing IMRT with the modified PWT, both techniques provided satisfactory coverage. The conformity indexes (CI) with IMRT (CI1: 0.71 +/- 0.02; CI2: 0.64 +/- 0.02) were better than those with the modified PWT (CI1: 0.50 +/- 0.02; CI2: 0.45 +/- 0.02). The mean dose, V(5), V(10) and V(5-10) of heart and left lung with the modified PWT were significantly lower than those with the IMRT. The mean dose and V(D2%) of contralateral breast with the modified PWT were not significantly different from the IMRT (P = 0.868 and P = 0.212). CONCLUSIONS: No single technique provides both the best CW and IMN coverage with minimum lung and heart dose. The modified PWT technique can be used as a clinical tool for the treatment of the left-sided post-mastectomy breast cancer patients to provide homogeneous target coverage while maintaining low doses to normal tissue. PMID- 21034592 TI - Hyalinizing trabecular tumor and papillary carcinoma of the thyroid. AB - BACKGROUND: Hyalinizing trabecular tumor (HTT) is a rare thyroid neoplasm, which shares some histologic features with thyroid papillary carcinoma (TPC). Clinically, it is frequently misdiagnosed as papillary carcinoma, even for some experienced pathologists. The aim of this study was to investigate whether HTT is variant of TPC or HTT is an independent entity of thyroid neoplasm. METHODS: The expression of CK19, galectin-3, HBME-1 and MIB-1 was detected by immunohistochemical staining in 12 cases of hyalinizing trabecular tumor and 20 cases of thyroid papillary carcinoma. RESULTS: Two of the 12 HTT samples were positive or focally positive for CK19. Four of the 12 samples of HTT presented positive to galectin-3; 3 were stained strongly and the other one was focally positive. None of the 12 samples of HTT was positive for HBME-1. Five in 12 HTT samples were stained in nucleus for MIB-1. Almost all the 20 cases of thyroid papillary carcinoma were intensely stained for CK19, galectin-3 and HBME-1. Fifteen in 20 cases of thyroid papillary carcinoma showed nuclear staining for MIB-1. CONCLUSIONS: HTT is an independent thyroid neoplasm, not a variant of TPC. This study could help in the differential diagnosis of HTT from TPC. CK19, galectin-3 and HBME-1 are adequate to identify HTT and TPC, but MIB-1 does not play an important role in discrimination between HTT and TPC. PMID- 21034593 TI - Evaluation of serum specific IgE for the diagnosis of allergic rhinitis with multi-allergens. AB - BACKGROUND: Objective evaluation of allergic rhinitis (AR) requires in vivo and in vitro tests. In vitro tests are important to assist or ensure the main allergens in multi-allergen-sensitive patients. The aim of this study was to evaluate the utility of serum specific IgE (sIgE) in the diagnosis of AR patients with multi-allergens in the Chinese population. METHODS: Combining a positive skin prick test (SPT) and clinical history as the diagnostic reference criteria of AR, we estimated concentrations of sIgE produced in response to the 7 most frequent allergens among 85 AR patients, using the UniCAP assay system. RESULTS: Among 85 individuals with positive SPT results and allergen-specific nasal symptoms, sIgE concentration correlated well with SPT classes among all the tested allergens. Based on a clinical diagnosis and SPT results using a positive cut-off value of a class 1 score, the CAP test performed well and the sensitivity for different allergens ranged from 0.5 (giant ragweed) to 0.91 (Dermatophagoides pteronyssinus (Der p) and Dermatophagoides farinae (Der f), while specificity ranged from 0.93 (Der f) to 1.0 (animal hair, Der p and mugwort). When the cut off score was adjusted to class 2, the sensitivity showed an increase overall while the remaining assessed items, including specificity, positive predictive value, negative predictive value and efficiency, showed an unacceptable decline. CONCLUSIONS: Well-established serum sIgE tests correlated well with SPTs. Setting a class 1 cut-off for positivity of SPT results was better than a class 2 setting for assessing the AR diagnostic value. PMID- 21034594 TI - Risk factors for interstitial cystitis/painful bladder syndrome in patients with lower urinary tract symptoms: a Chinese multi-center study. AB - BACKGROUND: Despite 100 years of research, the continued absence of well established risk factors impedes the diagnosis and treatment of interstitial cystitis/painful bladder syndrome (IC/PBS). We aimed to identify risk factors in patients with lower urinary tract symptoms (LUTS) without urinary tract infection or benign prostate hyperplasia in China. METHODS: A total of 397 outpatients with LUTS presenting for care to urology clinics in several hospitals throughout China were surveyed using a standardized questionnaire and validated outcome measures. The definitions for painful bladder syndrome based on the O'Leary-Sant interstitial cystitis symptom and problem indices were used. The prevalence of possible risk factors was analyzed using the Fisher's exact test and Pearson chi square test, and multivariate predictive models were developed using binary Logistic regression methods. RESULTS: Of those multi-centre patients surveyed, including 174 women and 223 men, 41% (162/397) met criteria for painful bladder syndrome. There was a significant difference between women and men (55% (95/174) vs. 30% (67/223), P < 0.001). Women with IC/PBS were more likely than those without IC/PBS to report a history of gynecological infections (odds ratio (OR): 2.85; 95% confidence interval (CI): 1.32 - 6.16, P = 0.007), intake of stimulatory foods (OR: 3.52; 95%CI: 1.50 - 8.30; P = 0.004), irritable bowel (OR: 3.46; 95%CI: 1.22 - 9.80; P = 0.014) and/or anorectal disease (OR: 2.68; 95%CI: 1.12 - 6.40, P = 0.023). After adjusting for confounding factors, bladder pain was significantly associated with stimulatory foods (OR: 3.85; 95%CI: 1.58 - 9.36, P = 0.003) and anorectal disease (OR: 2.76; 95%CI: 1.09 - 7.04, P = 0.03) in women. Caffeine beverage intake (OR: 3.54; 95%CI: 1.54 - 8.12, P = 0.003) was identified the only modifiable association noted in multivariate analysis of men. CONCLUSIONS: We found that stimulatory foods, anorectal disease and caffeine beverages are potential risk factors for IC/PBS. Further studies are necessary to determine their role in the pathogenesis of this disorder. PMID- 21034595 TI - A modified technique of bone grafting pedicled with femoral quadratus for alcohol induced osteonecrosis of the femoral head. AB - BACKGROUND: Quadratus femoris pedicled bone grafting has yielded satisfactory long-term clinical outcome for osteonecrosis of the femoral head (ONFH) in pre collapse ONFH without extensive lesion. However, for pre-collapse ONFH with extensive necrotic area, it is still challenging to preserve the femoral head. The current study aimed to introduce a new technique of deliquesce strut with titanium mesh containing bone grafting pedicled with the femoral quadratus and to evaluate its short-term outcomes. METHODS: From January 2008 to December 2008, 10 ONFH patients (12 hips) underwent operations by a new technique of deliquesce strut with titanium mesh containing bone grafting pedicled with the femoral quadratus (group A). According to the ARCO classification system, there were two hips in stage II B and 10 hips in stage II C. Also in the same period, 12 ONFH patients (16 hips) underwent operations by the conventional procedure of quadratus femoris pedicled bone grafting (group B). There were 6 hips in stage II B and 10 hips in stage II C. All patients were males and suffered from alcohol induced ONFH. For the new technique, the necrotic area was evaluated, and a titanium mesh piece of the same size (range from 2.5 cm * 2.8 cm to 2.8 cm * 3.4 cm) was obtained and shaped to match the contour of the head. The cancellous bone was first placed underneath the subchondral bone and was densely impacted (about 1 to 2 mm thick). Then the titanium mesh piece was inserted. The length of the decompressive trough was measured. A titanium cylinder mesh cage with a diameter of 1.6 cm of the same length was obtained, with a "U" shaped window in the wall being created to make room for the muscle pedicle. The muscle pedicle bone was inserted into the titanium mesh cage to form a bone graft-titanium cage complex and, then the complex was inserted. The hundred percent score method was used for outcome evaluation. Clinical and radiographic outcomes were compared between group A and group B. RESULTS: The average operative time was 150 minutes (130 to 185 minutes) in group A, with an average of 130 minutes (120 to 180 minutes) in group B. The mean blood loss was 400 ml (300 to 500 ml) in group A and 350 ml (250 to 500 ml) in group B. Group A patients were followed up for an average of 19.2 months (14 to 24 months), with an average of 18.5 months (12 to 24 months) for Group B. Full weight bearing was allowed 5 to 7 months postoperatively. Pain and function were obviously improved. For group A, pain score improved from a mean of 9.8 points preoperatively to an average of 24.6 points postoperatively, and function score improved from a mean of 9.0 points preoperatively to an average of 17.4 points postoperatively. In group B, pain score improved from a mean of 9.5 points preoperatively to an average of 24.2 points postoperatively and function score improved from a mean of 9.2 points preoperatively to an average of 17.2 points postoperatively. The range of motion changed the least, with score improvement from a preoperative mean of 13.9 points to postoperative 16.8 points for group A and from a preoperative mean of 13.7 points to postoperative 16.5 points for group B. Radiographic score improved from preoperative 31 points to postoperative 38 points for group A, in comparison with an improvement from preoperative 31 points to postoperative 37 points for group B. At the latest follow up, 11 hips were rated as excellent and 1 hip was better for group A, with 14 hips being rated as excellent and 2 hips being better in group B. There was no statistically significant difference between groups A and B in clinical and radiographic outcomes. CONCLUSION: For ONFH in stage ARCO IIC, satisfactory clinical outcome can be achieved by the new technique in the short term period while the long-term clinical outcome has yet to be determined. PMID- 21034596 TI - Voxel-based statistical analysis of cerebral glucose metabolism in patients with permanent vegetative state after acquired brain injury. AB - BACKGROUND: Permanent vegetative state is defined as the impaired level of consciousness longer than 12 months after traumatic causes and 3 months after non traumatic causes of brain injury. Although many studies assessed the cerebral metabolism in patients with acute and persistent vegetative state after brain injury, few studies investigated the cerebral metabolism in patients with permanent vegetative state. In this study, we performed the voxel-based analysis of cerebral glucose metabolism and investigated the relationship between regional cerebral glucose metabolism and the severity of impaired consciousness in patients with permanent vegetative state after acquired brain injury. METHODS: We compared the regional cerebral glucose metabolism as demonstrated by F-18 fluorodeoxyglucose positron emission tomography from 12 patients with permanent vegetative state after acquired brain injury with those from 12 control subjects. Additionally, covariance analysis was performed to identify regions where decreased changes in regional cerebral glucose metabolism significantly correlated with a decrease of level of consciousness measured by JFK-coma recovery scale. Statistical analysis was performed using statistical parametric mapping. RESULTS: Compared with controls, patients with permanent vegetative state demonstrated decreased cerebral glucose metabolism in the left precuneus, both posterior cingulate cortices, the left superior parietal lobule (P(corrected) < 0.001), and increased cerebral glucose metabolism in the both cerebellum and the right supramarginal cortices (P(corrected) < 0.001). In the covariance analysis, a decrease in the level of consciousness was significantly correlated with decreased cerebral glucose metabolism in the both posterior cingulate cortices (P(uncorrected) < 0.005). CONCLUSION: Our findings suggest that the posteromedial parietal cortex, which are part of neural network for consciousness, may be relevant structure for pathophysiological mechanism in patients with permanent vegetative state after acquired brain injury. PMID- 21034597 TI - No-reflow protection and long-term efficacy for acute myocardial infarction with Tongxinluo: a randomized double-blind placebo-controlled multicenter clinical trial (ENLEAT Trial). AB - BACKGROUND: No-reflow after emergency percutaneous coronary intervention (PCI) for acute ST segment elevation myocardial infarction (STEMI) is related to the severe prognosis. The aim of this study was to evaluate the efficacy of Tongxinluo, a traditional Chinese medicine, on no-reflow and the infarction area after emergency PCI for STEMI. METHODS: A total of 219 patients (female 31, 14%) undergoing emergency PCI for STEMI from nine clinical centers were consecutively enrolled in this randomized, double-blind, placebo-controlled, multicenter clinical trial from January 2007 to May 2009. All patients were randomly divided into Tongxinluo group (n = 108) and control group (n = 111), given Tongxinluo or placebo in loading dose 2.08 g respectively before emergency PCI with aspirin 300 mg and clopidogrel 300 mg together, then 1.04 g three times daily for six months after PCI. The ST segment elevation was recorded by electrocardiogram at hospitalization and 1, 2, 6, 12, 24 hours after coronary balloon dilation to evaluate the myocardial no-flow; myocardial perfusion scores of 17 segments were evaluated on day 7 and day 180 after STEMI with static single-photon emission computed tomography (SPECT) to determine the infarct area. RESULTS: There was no statistical significance in sex, age, past history, chest pain, onset-to reperfusion time, Killip classification, TIMI flow grade just before and after PCI, either in the medication treatment during the follow up such as statin, beta blocker, angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) between two groups. There was significant ST segment restoration in Tongxinluo group compared to the control group at 6 hours ((-0.22 +/- 0.18) mV vs. (-0.18 +/- 0.16) mV, P = 0.0394), 12 hours ((-0.24 +/- 0.18) mV vs. (-0.18 +/ 0.15) mV, P = 0.0158) and 24 hours ((-0.27 +/- 0.16) mV vs. (-0.20 +/- 0.16) mV, P = 0.0021) reperfusion; and the incidence of myocardial no-reflow was also reduced significantly at 24-hour reperfusion (34.3% vs. 54.1%, P = 0.0031). The myocardial perfusion scores of 17 segments evaluated by static SPECT was improved significantly on day 7 and day 180 after STEMI in Tongxinluo group compared to the control group (0.61 +/- 0.40 vs. 0.76 +/- 0.42, P = 0.0109 and 0.51 +/- 0.42 vs. 0.66 +/- 0.43, P = 0.0115, respectively). There was no significant difference in severe adverse events between two groups. CONCLUSION: Tongxinluo as a kind of traditional Chinese medicine could reduce myocardial no-reflow and infarction area significantly after emergency PCI for STEMI with conventional medicine therapy. PMID- 21034598 TI - Surgical strategies for petroclival meningioma in 57 patients. AB - BACKGROUND: Resection of petroclival meningioma (PCM) is difficult for neurosurgeons and usually brings poor performance status. In this study, we evaluated the possible risk factors for unfavorable clinical outcomes of surgical treatment of PCM, and tried to explore the optimal surgical strategies for better postoperative quality of life. METHODS: We recruited 57 patients (14 male, 43 female, mean age, 50.5 years) who underwent surgical resection of PCM in Huashan Hospital during 2002 - 2006. The primary outcomes including postoperative neurological deficits, modified Rankin scale (mRS) score and recurrence rate were evaluated, and all potential risk factors were assessed by the chi(2) test. Odds ratio and 95% confidence interval were calculated by univariate Logistic regression. The mean follow-up time was 34 months. RESULTS: Gross total resection was achieved in 58% of patients. One patient died during the perioperative period because of intracranial hemorrhage. Sixty-seven percent of patients experienced new postoperative neurological deficits and 26% had a higher mRS score at follow up assessment. Postoperative complications were observed in 24 patients. Within the follow-up period, radiographic recurrence occurred in 12.3% of patients at a mean follow-up of 42 months. Postoperative radiosurgery was administered to 19 patients who had residual tumors or recurrence and no further progression was found. Tumor adhesion, hypervascularity and engulfment of neurovascular structures were three risk factors for increased mRS score (P = 0.0002; P = 0.0051; P = 0.0009). Tumor adherence to adjacent structures clearly affected the extent of resection (P = 0.0029). The risk of postoperative cranial nerve deficits increased with tumor engulfment of neurovascular structures (P = 0.0004). CONCLUSIONS: Intraoperatively defined tumor characteristics played a critical role in identifying postoperative functional status. An individual treatment strategy after careful preoperative evaluation could help improve quality of life. PMID- 21034599 TI - Identification of a novel lethal fibrillin-1 gene mutation in a Chinese Marfan family and correlation of 3' fibrillin-1 gene mutations with phenotype. AB - BACKGROUND: Mutations in the fibrillin-1 gene have been identified in patients with Marfan syndrome (MFS). This study aimed to identify the molecular defects in the fibrillin-1 gene in a Chinese family with Marfan syndrome, accompanied by aortic aneurysms/dissection. METHODS: Two patients and one non-carrier in the family underwent complete physical, ophthalmic, and cardiovascular examinations. Genomic DNA was extracted from leukocytes of venous blood of these individuals in the family as well as 50 healthy normal controls. Polymerase chain reaction amplification and direct sequencing of all 65 coding exons of fibrillin-1 gene were analyzed. RESULTS: We found a novel mutation (c.8547T > G, p.Tyr2849X) in exon 65 of fibrillin-1 gene in a Chinese proband with Marfan syndrome, accompanied by aortic aneurysms/dissection. Sudden death at a young age of affected members was seen due to aortic aneurysms/dissection. By evaluating genotype-phenotype correlations of patients with mutations in the 3' end of fibrillin-1 gene (exons 64 and 65), we also found that the presence of nonsense mutations occurring in exons 64 and 65 appeared to be an indicator of early-onset aortic risk and sudden death. CONCLUSIONS: These results expand the mutation spectrum of fibrillin-1 gene and help in the study of the molecular pathogenesis of Marfan syndrome, indicating that mutations occurring in the 3' end of fibrillin-1 gene may play an independent functional role in the pathogenesis of Marfan syndrome. PMID- 21034600 TI - Spermatozoal protein profiles in male infertility with asthenozoospermia. AB - BACKGROUND: Infertility is a major medical and social problem, and elementary research on the spermatozoal proteins and their functions are relatively scarce and there are very few confirmed and effective options for the treatment of male infertility. Thus, it is essential to find candidate proteins that affect male infertility. This study was designed to detect the proteins with differential expression in sperm from infertile patients and normal donors. METHODS: Semen samples from patients with idiopathic asthenozoospermia (n = 114) and from fertile men with normal spermiograms (n = 37) were collected. Semen sample analysis, sperm protein extraction, SDS-PAGE electrophoresis and Western blotting analysis were performed. Results were analyzed by SPSS 16.0 statistical software. RESULTS: Western blotting analysis of spermatic proteins displayed a major differentially expressed protein in spermatozoa from fertile and idiopathic asthenozoospermia patients. Densities and volumes of the identified protein in the patients were significantly decreased compared to normal donors (P = 0.034 and P = 0.036, respectively). The protein was identified as DEAD-box protein 4 (DDX4, VASA). The expression and correction value (CV) of DDX4/VASA in the patients was reduced significantly compared to normal donors (P = 0.037 and P = 0.031, respectively). CONCLUSIONS: The expression of spermatic protein DDX4/VASA associates with spermatic motility, implying that DDX4/VASA may be a candidate marker for evaluation of spermatic motility. PMID- 21034601 TI - Characterization of a small molecule inhibitor of tumor necrosis factor-alpha production. AB - BACKGROUND: Numerous studies have shown that reducing the level of tumor necrosis factor-alpha (TNFalpha) through the use of anti-TNF antibodies or soluble TNF receptor is a safe and efficacious treatment to inflammatory diseases such as rheumatoid arthritis. Therefore, novel approaches to achieve this outcome are desired. The aim of this study was to investigate the characterization of a small molecule inhibitor, Y316, which blocks TNF mRNA upregulation and TNF production by lipopolysaccharides (LPS) stimulated monocytes. METHODS: Peripheral blood mononuclear cells (PBMC) from healthy volunteers were plated in 24-well plates and stimulated with LPS (1 ug/ml), phorbol-12-myristate-13-acetate (PMA) (100 ng/ml), zymosan (10 ug/ml) and Tsst (100 ng/ml). Supernatants were collected after 4-hour culture at 37 degrees C, and quantitative determination of TNFalpha, interleukin-1beta (IL-1beta), IL-6, IL-8, IL-10 and IL-2 production in the supernatants was performed by colorimetric enzyme-linked immunosorbent assay (ELISA). Total RNA of PBMC was isolated and cytokine mRNA quantitation was performed by using a RNA level measuring kit (R & D Systems). PBMC were pretreated with Y316 (10 umol/L, 1 umol/L, 0.1 umol/L, 0.01 uol/L and 0.001 umol/L) or dimethyl sulfoxide at 37 degrees C for 10 minutes, and then stimulated with LPS or PMA, protein concentrations of p44.42, IKBalpha, P38 and Jun NH2 terminal kinase were determined by Western blotting. Cyclic adenosine-3',5' monophosphate (cAMP) of PBMC was measured by enzyme immunoassay kit (Amersham Pharmacia Biotech). RESULTS: Y316 blocked TNF production and inhibited the upregulation of TNF mRNA levels in response to LPS, and also prevented the production of IL-1 and IL-6. In contrast, Y316 augmented the production of IL-10 in LPS-stimulated monocytes. Y316 failed to prevent the production of IL-2 and TNF in antigen-stimulated T cells, suggesting that its effects may be cell-type specific. Y316 prevented the phosphorylation and activation of the MAPK, ERK, and therefore appeared to mediate its effects on TNF by acting at an early point in the signaling cascade induced in response to LPS. There was no effect of Y316 on cAMP levels either alone or in the presence of LPS. CONCLUSIONS: Y316 appears to be a small molecule inhibiting TNF production, which may act via a novel mechanism. Identification of the target of Y316 may lead to the development of alternative strategies for achieving selective cytokine inhibition. PMID- 21034602 TI - Clinical features and long-term prognosis of patients with anomalous origin of the left coronary artery from the pulmonary artery. AB - BACKGROUND: Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital heart anomaly. We aimed to illustrate the clinical features and long-term prognosis of patients with ALCAPA. METHODS: Twenty three patients (13 males and 10 females, ages ranging from 2.5 months to 65 years) identified as ALCAPA in Beijing Anzhen Hospital from April 1984 to June 2009 were divided into two groups, based on the age of onset: group 1 (<= 12 months, n = 16) and group 2 (> 12 months, n = 7). RESULTS: Fifty six point three percent of patients in group 1 had been misdiagnosed as endocardial fibroelastosis (9/16), 18.8% as dilated cardiomyopathy (3/16) and 6.3% as myocardial infarction (1/16). Patients in group 2 were usually diagnosed as coronary heart disease, myocarditis, or patent ductus arteriosus. Electrocardiography in group 1 revealed abnormal Q waves with T wave inversion in leads I, avL, V(4)-V(6), especially in lead avL (deep and wide Q wave); but no specific manifestations in group 2. A higher percentage of patients in group 1 had cardiomegaly on chest radiograph (86.7% vs. 33.3%, P = 0.031), while pulmonary artery protrusion was more common in group 2 (26.7% vs. 83.3%, P = 0.046). Lower left ventricular ejection fraction (LVEF) was present in group 1 than in group 2 ((48.5 +/- 11.5)% vs. (65.0 +/- 6.1)%, P < 0.001). Apical ventricular aneurysm (62.5% vs. 0%, P = 0.007), enhanced echogenicity of papillary muscles (87.5% vs. 28.6%, P = 0.011) and endocardial thickening (93.8% vs. 14.3%, P < 0.001) were more frequent in group 1 than in group 2. The ratio of the proximal right coronary artery (RCA) diameter to the aortic root diameter exceeded 0.14 in all cases, more prominent in group 2 (0.26 +/- 0.05 vs. 0.33 +/- 0.03, P = 0.009). Increased coronary artery collaterals within the interventricular septum were detected in 18 patients (78.3%) by Doppler imaging. Twenty one patients underwent cardiac surgery, including left coronary artery (LCA) ligation (1/21), LCA ligation plus coronary artery bypass grafting (1/21), Takeuchi operation (7/21), and LCA reimplantation surgery (12/21). Four patients underwent concomitant mitral valve repair and one received mitral valve replacement. Aneurysm resection was performed in 3 cases. Six patients died in hospital after surgery, and the rest of the cohort had no overt symptoms during a follow-up period of 6 to 166 months. Their abnormal Q waves gradually regressed or disappeared, and the LVEF and left ventricle size returned to normal range with alleviation of mitral insufficiency. CONCLUSIONS: The accurate diagnosis of ALCAPA can be made with serial diagnostic methods. ALCAPA can be successfully treated with several types of cardiac surgery, and surgeries of establishing two coronary-artery circulation are the preferred operations nowadays, with good long term prognosis. PMID- 21034603 TI - Airborne fine particulate matter induced pulmonary inflammation as well as oxidative stress in neonate rats. AB - BACKGROUND: Airborne fine particulate matter (PM) can induce pulmonary inflammation which may adversely affect human health, but very few reports about its effect on the neonate rats are available. This study aimed to observe the potential impact and toxicity of fine PMs on the airway in neonate rats. METHODS: Pulmonary inflammation, cytotoxicity, histopathology, and antioxidants as well as oxidant products were assessed 24 hours after intratracheal instillation of fine PM consecutively for 3 days. Cytotoxicity of fine PM was measured in HEp-2 cells. RESULTS: Rats treated with high dose fine PM developed significant pulmonary inflammation characterized by neutrophil and macrophage infiltration. The inflammatory process was related to elevated level of TNF-alpha and prooxidant/antioxidant imbalance in the lung. Cytotoxicity studies performed in human epithelial cells indicated that high dose fine PM significantly reduced cell viability. CONCLUSION: The study demonstrated acute exposure to fine PM induced airway inflammation as well as increased oxidative stress in addition to its direct toxic effect on airway epithelium cells. PMID- 21034604 TI - Inhibition of survivin expression and mechanisms of reversing drug-resistance of human lung adenocarcinoma cells by siRNA. AB - BACKGROUND: Survivin, a member of the inhibitor of apoptosis protein (IAP) family, overexpresses in tumor cells and not expresses in terminally differentiated adult tissues. This study aimed to investigate the effects of survivin-specific siRNA on cell proliferation, apoptosis and chemosensitivity to cisplatin in vitro and in vivo and explore the mechanisms about decreasing expression of survivin in reversing cancer cells resistance to chemotherapeutic drug. METHODS: Survivin-specific siRNA was transfected into A549/DDP cells. The expression of survivin and lung resistance-related protein (LRP) mRNA levels were determined by RT-PCR, chemosensitivity of A549/DDP (cisplatin) cells to cisplatin was determined by MTT assay, and apoptosis and cell cycle were determined by flow cytometry (FCM). The protein expression levels of survivin, LRP, cyclin-D(1), caspase-3 and bcl-2 were determined by Western blotting analyses. The effect of survivin siRNA inhibition on tumor growth was studied in athymic nude mice in vivo. RESULTS: Survivin-specific siRNA efficiently down-regulated survivin expression. The cell cycle was arrested at G2/M phase, and apoptosis was obviously found. Inhibition of survivin expression could make the IC50 and drug resistant index of cisplatin decrease, and enhance the cancer cells sensitivity to cisplatin. After transfection by survivin-specific siRNA, expression of LRP and cyclin-D1 were downregulated, caspase-3 expression was upregulated, bcl-2 expression had no obvious change. The animal experiment confirmed knockdown of survivin could inhibit the tumor growth. CONCLUSIONS: Survivin-specific siRNA can efficiently suppress the expression of survivin, increase apoptosis, inhibit cells proliferation and enhance the chemosensitivity to cisplatin in vitro and in vivo. Suppression of survivin expression helping to reverse drug-resistance may have relationship with downregulation of LRP and upregulation of caspase-3. Anti tumor strategies based on the inhibition of survivin may be useful in targeting lung adenocarcinomas. PMID- 21034605 TI - Intensive glycemic control and macrovascular events in type 2 diabetes mellitus: a meta-analysis of randomized controlled trials. AB - BACKGROUND: There is no agreement as to whether intensive glucose control in type 2 diabetes can reduce the incidence of macrovascular events in these patients. We performed a meta-analysis comparing intensive glucose control or conventional glucose control in randomized controlled trials. METHODS: Databases including MEDLINE, EMBASE, and Cochrane controlled trials register, the Cochrane Library, and Science Citation Index were searched to find relevant trials. Outcome measures were the incidence of major macrovascular events. RESULTS: Six trials involving 28 065 patients were included. Analysis suggested that there was an obviously decreased incidence of major macrovascular events in patients having intensive glucose treatment vs. controls (RR 0.92; 95%CI 0.87, 0.98; P = 0.005). However, intensive glycemia control strategies in type 2 diabetes showed no significant impact on the incidence of death from any cause compared with conventional glycemia control strategies, intensive 14.7%, controls 12.0% (RR 0.95; 95%CI 0.80, 1.12; P = 0.55), as well as on the incidence of cardiovascular death, intensive 3.7%, controls 3.6% (RR 1.10, 95%CI 0.79, 1.53; P = 0.57). CONCLUSIONS: Control of glycemia to normal (or near normal levels) in type 2 diabetes appears to be effective in reducing the incidence of major macrovascular events, but there were no significant differences of either the mortality from any cause or from cardiovascular death between the two glycemia-control strategies. PMID- 21034606 TI - Protective strategies to prevent patent ductus arteriosus. PMID- 21034607 TI - Lung fluid during postnatal transition. PMID- 21034608 TI - Improving fetal to neonatal transition of the very preterm infant: novel approaches. PMID- 21034609 TI - Retinopathy of prematurity: an epidemic in the making. AB - OBJECTIVE: To explore the etiology, incidence and methods to prevent and treat severe retinopathy of prematurity (ROP), which is rapidly becoming a threat to the vision of babies in areas of the world where increasing numbers of premature babies are surviving. DATA SOURCES: The data used in this review were mainly from Medline and PubMed published in English. The search term was "retinopathy of prematurity and premature birth". STUDY SELECTION: We discuss the historical perspectives, prevalence and incidence, classification and treatment methods of ROP in premature babies. RESULTS: Peripheral retinal ablation for eyes with severe ROP can help prevent progression to blindness and several large clinical trials have shown the effectiveness of this treatment in high risk eyes. As a greater proportion of VLBW and ELBW babies survive, the population of babies at risk increases. In various regions of the world, different identification criteria are used to determine which babies are at risk of blindness in order to provide timely diagnostic examinations and treatment as needed. Methods for preventing ROP include better ante-natal and obstetric care leading to a reduction in the rate of prematurity, the use of ante-natal corticosteroids, and better neonatal care practices. Recent developments have indicated that management of oxygen supplementation is important for the prevention of severe ROP; however, there is not yet known what oxygen saturation target should be adopted. Sepsis increases severe ROP in very preterm infants. Genetic associations and a telemedicine approach may be explored to detect ROP. Treatment of anti-VEGF therapy are potentially useful in eyes with severe ROP, but long term effects are not yet known and such treatment should be used with great caution. CONCLUSIONS: ROP is a potentially binding disease for premature babies which is becoming more prevalent with the development improving neonatal services in many countries in recent years. High priority should be placed on developing approaches to prevent ROP blindness by reducing preterm birth, improving care of premature babies in neonatal care units, and providing adequate ophthalmological services in those regions. PMID- 21034610 TI - Oxygen administration in the care of neonates: a double-edged sword. AB - OBJECTIVE: To evaluate the use of oxygen in neonates in the past, present and future. DATA SOURCES: The data are mainly from Pubmed with relevant published articles from the 1940s to the present with some information gathered from web searches. STUDY SELECTION: Studies evaluating the use of oxygen in premature and term infants through history with original milestone articles included. RESULTS: There are still many unknowns about the proper use of oxygen in preterm and term infants but many studies suggest that both liberal use (resulting in a blood oxygen saturation of greater than 94%) as well as restrictive use (resulting in a blood oxygen saturation of less than 80% - 85%) are detrimental and have long term consequences on the infant. CONCLUSIONS: Definitive studies evaluating the appropriate concentration and duration of supplemental oxygen are ongoing and will help in the management of term and preterm infants requiring oxygen. PMID- 21034611 TI - Evaluation and management of inherited disorders of surfactant metabolism. AB - OBJECTIVE: To review the pathophysiology, evaluation, management, and outcomes of children with inherited disorders of surfactant metabolism due to mutations in the genes encoding surfactant proteins-B or -C (SFTPB, SFTPC), ATP binding cassette member A3 (ABCA3), and thyroid transcription factor (NKX2.1). DATA SOURCES: Review of the literature, previous work from the author's and collaborators' laboratories, St. Louis Children's Hospital Lung Transplant Database. STUDY SELECTION: Key articles in the field, author's work. RESULTS: Inherited disorders of surfactant metabolism present as acute, severe respiratory dysfunction in the neonatal period (SFTPB, ABCA3, NKX2.1) or as chronic respiratory insufficiency in later infancy and childhood which is of variable onset, severity, and course (SFTPC, ABCA3, NKX2.1). Diagnosis is established with sequencing the relevant genes; lung biopsy with electron microscopy is a useful adjunct. For surfactant protein-B and ABCA3 deficiency presenting with acute neonatal disease, treatment options are limited to lung transplantation or compassionate care. For the more chronic presentations of surfactant protein-C, ABCA3, and NKX2.1 associated disease, the natural history is variable and therefore individualized, supportive care is appropriate, CONCLUSIONS: Inherited disorders of surfactant metabolism are rare, but informative diseases that provide unique opportunities for understanding mechanisms of respiratory disease in newborns and children. PMID- 21034613 TI - Bronchopulmonary dysplasia: pathogenesis, risk factors and early prevention strategies. PMID- 21034612 TI - Epigenetics in neonatal diseases. AB - OBJECTIVE: To review the role of epigenetic regulation in neonatal diseases and better understand Barker's "fetal origins of adult disease hypothesis". DATA SOURCES: The data cited in this review were mainly obtained from the articles published in Medline/PubMed between January 1953 and December 2009. STUDY SELECTION: Articles associated with epigenetics and neonatal diseases were selected. RESULTS: There is a wealth of epidemiological evidence that lower birth weight is strongly correlated with an increased risk of adult diseases, such as type 2 diabetes mellitus, hypertension, and cardiovascular disease. This phenomenon of fetal origins of adult disease is strongly associated with fetal insults to epigenetic modifications of genes. A potential role of epigenetic modifications in congenital disorders, transient neonatal diabetes mellitus (TNDM), intrauterine growth retardation (IUGR), and persistent pulmonary hypertension of the newborn (PPHN) have been studied. CONCLUSIONS: Acknowledgment of the role of these epigenetic modifications in neonatal diseases would be conducive to better understanding the pathogenesis of these diseases, and provide new insight for improved treatment and prevention of later adult diseases. PMID- 21034614 TI - Nasal continuous positive airway pressure combined with surfactant and NO for treatment of respiratory distress syndrome, prevention of bronchopulmonary dysplasia, and brain protection. PMID- 21034615 TI - Coronary interventions with unfamiliar equipments. PMID- 21034617 TI - Recent trends of study on esophageal variceal bleeding. PMID- 21034616 TI - Impact of migraine attacks on the blood-brain barrier. AB - BACKGROUND: Cortical spreading depression can cause migraine attack, and up regulate matrix metalloproteinase-9 (MMP-9) expression in animal. This study aimed to determine the impact on the structure and function of the blood-brain barrier by measuring plasma MMP-9 levels in patients at the acute and late stages of migraine attacks in order to elucidate the pathological mechanisms involved. METHODS: We recruited a case-control cohort of 38 adult migraine patients and 20 age- and gender-matched healthy control subjects. Five milliliter blood samples were collected at the acute and late stages of migraine (days 1 - 7), and also from the control subjects. Solid phase double antibody sandwich enzyme-linked immunosorbent assay was used to determine plasma MMP-9 levels. Statistical analysis was performed using the SAS version 9.1. RESULTS: Initial plasma MMP-9 levels of migraine patients were significantly higher than those of controls ((12.612 +/- 0.016) ug/L vs. (6.069 +/- 0.023) ug/L, respectively, P < 0.05). High MMP-9 expression was observed during days 1 - 6 of migraine attacks, with highest expression occurring on day 3 ((17.524 +/- 0.035) ug/L). During attacks, MMP-9 levels were similar in migraine patients with and without aura (P > 0.05); in addition, levels were not correlated with degree of headache pain (P > 0.05). CONCLUSIONS: We hypothesize that migraine could lead to increased plasma MMP-9 levels resulting in blood-brain barrier damage. MMP-9 levels increase during days 1 - 6 of migraine attacks, peaking on day 3. Therefore, MMP-9 could be used as a biological marker to guide treatment of migraine attacks. PMID- 21034618 TI - Role of RhoA in platelet-derived growth factor-BB-induced migration of rat hepatic stellate cells. AB - BACKGROUND: Although the migration of hepatic stellate cells (HSCs) is essential for hepatic fibrotic response, the detailed mechanisms involved are poorly understood. The aim of this study was to examine the role of Rho GTPases (especially RhoA) in platelet-derived growth factor (PDGF)-BB-induced migration of HSCs. METHODS: The migration of primary rat HSCs was evaluated using transwell Boyden chamber, while cytoskeletal changes were visualized by immunofluorescence staining of intracellular actins and vinculin. Quantitative real-time PCR and Western blotting analysis were used to detect the expression of Rho GTPases (RhoA, Rac1 and Cdc42) within HSCs and their activation was determined by glutathione S-transferase pull-down assay. Finally, the effects of RhoA on PDGF BB-induced cell migration and cytoskeletal remodeling were analyzed using HSC-T6 cells stably transfected with constitutively active (CA, Q63L) or dominant negative (DN, T19N) RhoA mutants. Data were analyzed using SPSS 16.0 software. Student's t test was used to analyze differences between two groups and one-way analysis of variance (ANOVA) was used among multiple groups. RESULTS: Rapid cytoskeletal remodeling led to a significant increase in the motility of primary rat HSCs after haptotactic (direct) and chemotactic (indirect) stimulation by PDGF-BB. PDGF-BB caused a dramatic elevation in the levels of both total and active RhoA protein. However, the levels of mRNA for Rho GTPases, including RhoA, Rac1 and Cdc42, were unaffected. Furthermore, PDGF-BB induced increased formation of stress fibers and focal adhesions in HSC-T6 cells transfected with CA-RhoA, but not in HSC-T6 transfected with DN-RhoA. Surprisingly, both CA- and DN-RhoA transfected HSC-T6 cells showed decreased migratory potential in the absence or presence of PDGF-BB compared with controls. CONCLUSIONS: PDGF-BB induced cytoskeletal remodeling in rat HSCs and promoted their migration via regulation of intracellular RhoA. RhoA may be one of the determinants in PDGF-BB-induced HSC migration. PMID- 21034619 TI - Effect of medical ozone therapy on renal blood flow and renal function of patients with chronic severe hepatitis. AB - BACKGROUND: Medical ozone therapy system was reported to have certain effects on the treatment of severe hepatitis, but its mechanism is not very clear. One of the causes of death of severe hepatitis is complication of renal damage or hepatorenal syndrome. The present study aimed to observe effects of medical ozone therapy system on plasma renin activity (PRA), angiotensin II (AII), aldosterone (ALD), renal blood flow and renal function of patients with chronic severe hepatitis and explore mechanisms of medical ozone therapy in the treatment of severe hepatitis. METHODS: Eighty-five cases with chronic severe hepatitis were randomly divided into ozone therapy group (43 cases) and control group (42 cases). The patients in the ozone therapy group were treated with basic treatments plus ozone therapy system. Basic autohemotherapy was used. One hundred milliliter venous blood was drawn from each patient, and was mixed with 100 ml (35 ug/ml) medical ozone and then was returned the blood to the patient intravenously, once every other day for 20 days. Only the basic treatments were given to the control group. PRA, AII, ALD, renal blood flow and damage to renal function of the two groups before treatment and 20 days after treatment were compared. Survival rates were also compared. RESULTS: Twenty days after the treatment, in ozone therapy group, PRA was (1.31 +/- 0.12) ng.ml-1.h-1, AII (111.25 +/- 17.35) pg/ml, ALD (251.31 +/- 22.60) pg/ml, which decreased significantly compared with those before treatment (PRA (2.23 +/- 0.13) ng.ml-1.h 1, AII (155.18 +/- 19.13) pg/ml, ALD (405.31 +/- 29.88) pg/ml, t = 4.67 - 14.23, P < 0.01), also lower than those of control group 20 days after the treatment (PRA (2.02 +/- 0.11) ng.ml-1.h-1, AII (162.21 +/- 15.32) pg/ml, ALD (401.20 +/- 35.02) pg/ml, t = 4.97 - 15.61, P < 0.01); renal blood flow was (175.15 +/- 28.20) ml/min, which increased compared with that before the treatment ((125.68 +/- 21.25) ml/min) and was higher than that of control group 20 days after the treatment ((128.59 +/- 23.15) ml/min, t = 4.78, 4.61, P < 0.01). Renal damage occurred in 2 cases (5%) in ozone therapy group, less than that in control group (9 cases, 21%) (chi2 = 5.295, P < 0.05). Thirty-three cases (77%) in ozone therapy group vs. 16 cases (38%) in control group survived (chi2 = 12.993, P < 0.01). CONCLUSIONS: Basic treatment plus medical ozone therapy for patients with chronic severe hepatitis could decrease PRA, AII and ALD levels significantly increase renal blood flow, prevent renal damage to certain extent and improve survival rate of the patients. PMID- 21034620 TI - Clinical and pathological studies of borderline gastrointestinal stromal tumors. AB - BACKGROUND: Borderline gastrointestinal stromal tumors (GISTs) are intermediate tumors between benign and malignant variants; however, the clinical and pathological features of borderline GISTs remain poorly defined. This study aimed to characterize GISTs and to identify a set of borderline criteria for practical use. METHODS: Medical records and specimens of 840 patients from 12 hospitals were retrospectively examined. Totally 485 and 76 patients with any of the parameters predictive of either malignant or benign tumors were excluded. The Kaplan-Meier method was used to calculate disease-free survival and overall survival rates. RESULTS: Among the remaining 279 borderline GIST patients, 223 were followed up for 1 to 31.48 years. Two patients developed local recurrence, and both were cured by subsequent operations alone. The 5-year disease-free survival and overall survival rates were 99% and 100%, respectively. Morphologically, borderline GISTs typically exhibited moderate cellularity, and subsets of them also showed moderate atypia, low mitotic activities, or large tumor size. According to the National Institutes of Health (NIH) consensus criteria, the risk levels of the 279 GISTs were classified to be very low to high. However, the disease-free survival rates were not significantly different among these risk groups (P = 0.681). CONCLUSIONS: The proposed borderline GIST criteria in the current study may complement the existing NIH criteria, based primarily on tumor size and mitotic count, in the evaluation of the biological behaviors of GISTs. Since a subset of borderline GISTs with high risk level showed favorable outcome, the introduction of the borderline GIST system may avoid overdiagnosis and over therapy. PMID- 21034621 TI - Effects of insulin-like growth factor binding protein-related protein 1 in mice with hepatic fibrosis induced by thioacetamide. AB - BACKGROUND: Insulin-like growth factor binding protein-related protein 1 (IGFBPrP1) can activate hepatic stellate cells and increase extracellular matrix (ECM) in vitro. However, the effects of IGFBPrP1 in mice with hepatic fibrosis, and the mechanisms of these effects, are currently unknown. We aim to address these issues in this study. METHODS: Intraperitoneal injection of thioacetamide (TAA) is a classic method for establishing a mouse model of hepatic fibrosis. Using this model, we administered anti-IGFBPrP1 antibody, again via intraperitoneal injection. The morphological changes of liver fibrosis were observed with both HE and Masson stainning. The immunohistochemical assays and Western blotting were used to measure changes in IGFBPrP1, alpha-smooth muscle actin (alpha-SMA) and ECM in liver tissues, and the expression of transforming growth factor-beta1 (TGF-beta1) and Smad3. Data were statistically analyzed using one-way analysis of variance (ANOVA), the SNK-q test for inter-group differences. RESULTS: The Masson staining analysis showed that compared with normal control group, content of collagen fiber in TAA5w group was significantly increased (P < 0.01), and it was significantly decreased in TAA5w/aIGFBPrP1 group compared with in TAA5w group (P < 0.01). The expression of hepatic IGFBPrP1, alpha-SMA, TGF beta1, Smad3, collagen I and fibronectin (FN) was significantly up-regulated in the TAA5w group (P < 0.01). Anti-IGFBPrP1 treatment reversed these changes (P < 0.01). CONCLUSIONS: IGFBPrP1 plays an important role in the development of hepatic fibrosis. Anti-IGFBPrP1 prevents fibrosis in mice by suppressing the activation of hepatic stellate cells, inhibiting the synthesis of major components of the ECM (namely, collagen I and FN). The mechanism for this suppression of fibrosis is associated with the TGF-beta1/Smad3 signaling pathways. PMID- 21034622 TI - Preliminary study on MR colonography with air enema in detection of colorectal neoplasms. AB - BACKGROUND: The few studies on MR colonography with air enema involved feasibility of bowel distention and imaging quality and lacked detection sensitivity of colorectal neoplasms. The purpose of this prospective study was to assess the detection sensitivity of colorectal neoplasms with the three dimensional Fourier transform fast spoiled gradient-recalled MR colonography with air enema. METHODS: A total of 30 patients scheduled for optical colonoscopy due to rectal bleeding, positive fecal occult blood test results or altered bowel habits were recruited and successfully underwent entire colorectal examinations with three-dimensional Fourier transform fast spoiled gradient-recalled MR colonography and subsequent optical colonoscopy on the same day. Detection sensitivity of colorectal neoplasms with MR colonography was statistically analyzed on a per-neoplasm size basis by using findings from optical colonoscopy and histopathological examinations as the reference standards. RESULTS: Seventy six neoplasms were detected with optical colonoscopy, consisting of 1 mm-5 mm (n = 11), 6 mm-9 mm (n = 29) and >= 10 mm (n = 36) in diameter. Detection sensitivities of 1 mm-5 mm, 6 mm-9 mm, >= 10 mm and >= 6 mm colorectal neoplasms with MR colonography were 9.1%, 75.9%, 100% and 89.2%, respectively; overall detection sensitivity for all sizes colorectal neoplasms was 77.6%. CONCLUSIONS: Detection sensitivity of three-dimensional Fourier transform fast spoiled gradient-recalled MR colonography with air enema is low for 1 mm-5 mm colorectal neoplasms, but the detection sensitivity is 89.2% for >= 6 mm neoplasms, and all >= 10 mm neoplasms could be detected. PMID- 21034623 TI - Mitral isthmus ablation in patients with prosthetic mitral valves. AB - BACKGROUND: Previous studies have investigated the technique of linear ablation at the mitral isthmus (MI) in patients with idopathic atrial fibrillation (AF), but MI ablation in patients with prosthetic natural mitral valves (MVs) was not described in detail. Present study sought to summarize our initial experience of ablating MI in patients with prosthetic MVs METHODS: Patients with drug refractory AF and prosthetic MVs were eligible for this study, and the patients with natural MVs but received MI ablation served as control group. Left atrium (LA) mapping and ablation was carried out guided by CARTO system. The anatomy of MI was assessed via computer topography scan. RESULTS: During the study period, a consecutive of 19 patients (male/female = 12/7, mean age of (48 +/- 6) years) with prosthetic MVs (16 with metal valves, 3 with biologic valves) entered for AF ablation, other 35 patients served as control group. In study group, mapping along MI documented lower voltages ((2.0 +/- 1.0) vs. (3.1 +/- 1.3) mV, P = 0.002), more fragmented potentials (19/19 vs. 20/15, P < 0.001), and higher impedance ((132 +/- 34) vs. (110 +/- 20) Omega, P = 0.004). After initial ablation, more residual gaps along the MI lesions were found in study group (2.4 +/- 0.4 vs. 1.7 +/- 0.3, P < 0.001). The mean length of MI ((6.2 +/- 3.3) vs. (7.1 +/- 2.3) cm, P = 0.25) was comparable between 2 groups, but the MI in study group was much thicker ((3.1 +/- 1.8) vs. (2.1 +/- 1.07) cm, P = 0.01) and all were found as pouch type (19/19 vs. 2/35, P < 0.001). The follow-up results were comparable (65.1% vs. 72.3%, P = 0.30). CONCLUSION: For patients with prosthetic MVs, linear ablation at MI could be successfully carried out despite anatomical and pathological changes. PMID- 21034624 TI - T allele at site 6007 of bone morphogenetic protein-4 gene increases genetic susceptibility to ossification of the posterior longitudinal ligament in male Chinese Han population. AB - BACKGROUND: Several candidate genes of ossification of the posterior longitudinal ligament (OPLL) susceptibility have been identified, but their polymorphisms account for only a small percent of the total variance. Bone morphogenetic protein-4 (BMP4) is a potent ectopic ossification inducing factor. BMP4 protein and mRNA are present in cells from OPLL patients, but not non-OPLL controls. A single nucleotide polymorphism of 6007C>T(rs17563) of BMP4 has been reported to affect bone density in postmenopausal women. Thus, BMP4 may function in OPLL development. Appropriately, the relationship between BMP4 polymorphisms and OPLL was investigated. METHODS: A case-control association study investigated the genetic etiology in 179 OPLL patients and 298 non-OPLL controls. Extent of OPLL was analyzed by radiologic examinations. Whether single nucleotide polymorphism (SNP) of -5826G>A(rs1957860) 5' of the transcription start site and 6007C>T(rs17563) in exon 4 of the BMP4 gene were statistically associated with genetic susceptibility to OPLL in Chinese Han subjects was assessed. RESULTS: A significant statistical difference in genotype of 6007C>T polymorphism between male OPLL patients and male controls was evident, and the frequency of "TT" genotype in male OPLL patients was significantly higher than in male controls (P = 0.039). The frequency of the "T" allele was also significantly higher in male OPLL subjects than in male controls (P = 0.014, OR = 1.57). A significant difference was also observed between the 6007C>T polymorphism and the number of ossified cervical vertebrae in OPLL patients, while no statistical difference was apparent between the -5826G>A polymorphism and OPLL occurrence. CONCLUSIONS: The T allele in the 6007C>T polymorphism may be a risk factor for male Han Chinese with ossification of the posterior longitudinal ligament in the cervical spine. Chinese Han male patients with CT and TT 6007C>T genotypes have a genetic susceptibility to OPLL and more extensive OPLL in the cervical spine. PMID- 21034625 TI - Population pharmacokinetics of rocuronium delivered by target-controlled infusion in adult patients. AB - BACKGROUND: Target-controlled infusion (TCI) has been recently developed and successfully implemented in clinical practice. The current study was to estimate the population pharmacokinetics of rocuronium TCI in adult patients using nonlinear mixed-effects model (NONMEM), and to investigate the influence of relevant factors in adult patients. METHODS: Fourteen ASA I-II patients undergoing elective laparoscopy operation with general anesthesia were included. After induction, all patients received rocuronium by TCI system. The beginning target plasma concentration (Cpt) was 2.0 ug/ml, then increased Cpt according to the neuromuscular transmission monitoring. The endpoint of Cpt was determined when the T1 scale was blocked by 90% - 95%. TCI rocuronium was stopped 30 minutes before the end of the operation. Arterial blood was drawn before anesthesia at 0, 2, 4, 6, 8, 10, 15, 20, 30, 45, 60, 120, 180, 240 and 360 minutes after the infusion of rocuronium was stopped for the analysis of plasma concentrations of rocuronium by liquid chromatography-mass spectrometry/mass spectrometry (LC MS/MS). The population pharmacokinetics analysis was performed using NONMEM program. RESULTS: The pharmacokinetics of TCI rocuronium in adult patients was best described by a three-compartment model. Pharmacokinetic parameters were clearance (CL)1 = 0.205 L/min, CL2 = 0.324 L/min, CL3 = 0.0292 L/min, volumes of distribution (V)1 = 4.00 L, V2 = 2.28 L, V3 = 4.26 L, Vdss = 10.54 L. Both age and weight as covariates affected the pharmacokinetic parameters. V1 and CL1 were negatively correlated with patient age. CL1 was positively correlated with weight. CONCLUSIONS: No pharmacokinetic change was noted when rocuronium was administered via TCI. Both age and weight as covariates affected the pharmacokinetic parameters. PMID- 21034627 TI - Detection of multiple antibodies in myasthenia gravis and its clinical significance. AB - BACKGROUND: Antibodies against acetylcholine receptor, acetylcholinesterase, ryanodine receptor and titin have been found in patients with myasthenia gravis. However, the relations between these antibodies and character of myasthenia gravis are unknown. This study aimed to detect multiple antibodies in myasthenia gravis and to investigate its clinical significance. METHODS: These antibodies were detected by enzyme-linked immunoabsorbent assay in 89 cases of myasthenia gravis, 66 cases of other neurological diseases and 66 healthy controls. The incidences of antibodies were compared using the chi-square test. RESULTS: Acetylcholine receptor, acetylcholinesterase, titin and ryanodine receptor antibodies were detected in 53.9%, 20.2%, 64.0% and 55.0% of myasthenia gravis patients respectively, higher than in patients of other neurological diseases and controls groups. The combination of the four antibodies assays provided 94.4% sensitivity and 84.0% specificity for the diagnosis of myasthenia gravis. Acetylcholinesterase antibody occurred more frequently in acetylcholine receptor antibody negative patients with adverse reactions to neostigmine test. Titin antibody provided 82.1% sensitivity and 52.5% specificity for myasthenia gravis with thymoma. Incidences of titin and of ryanodine receptor antibody were higher in late onset myasthenia gravis than in early onset myasthenia gravis. The proportion of titin antibody positive patients increased with the severity of myasthenia gravis as graded by a modified Osserman scale. CONCLUSIONS: Testing for acetylcholine receptor, acetylcholinesterase, titin and ryanodine receptor antibodies can offer a better diagnostic method for myasthenia gravis than each antibody test alone. Titin antibody combined with computed tomography was better for the diagnosis of thymoma. Titin antibody occurred most frequently in severe myasthenia gravis. PMID- 21034626 TI - Effect of antioxidants on amelioration of high-risk factors inducing hypertensive disorders in pregnancy. AB - BACKGROUND: This is a prospective clinical study based on a large sample gathered from multiple centers in China, subordinating to 10th Five-Year Plan of National Science & Technology Progression. We analyzed the high-risk factors inducing hypertensive disorders in pregnancy (HDP) and estimated the potential effect of anti-oxidants administration, including vitamin C (VC), vitamin E (VE) and Salvia Miltiorrhiza L (SML), a Chinese herb medicine, in amelioration of the high-risk factors in pregnancy. METHODS: From April 2005 to July 2006, 4814 pregnant women from 24 national wide cooperative hospitals were involved in this prospective research. The participants were randomly divided into two groups: 1607 cases were in anti-oxidants group with administration of vitamins and SML; 3207 cases were in control group without any medicine given. Every participant was under monitoring for the morbidity of HDP and the high-risk factors were investigated in HDP cases in each group. RESULTS: (1) The morbidity of HDP was 3.55% in anti oxidants group vs. 4.18% in control group. No statistical difference existed between the two groups (P > 0.05). (2) In anti-oxidants group, the HDP morbidities among three subgroups: VC + VE + SML, VC + VE and SML only, were 5.51%, 3.05% and 5% respectively. It showed no statistical difference among three remedies (P > 0.05). (3) The related index of factors affecting HDP showed in intensity sequence as follows: family HDP history > profession > education level > age > body weight. The incidence of HDP in normal population was 3.51%, and the incidence of HDP in high-risk pregnant women (family HDP history, heavy physical labor, low education level (middle school and below), age >= 40, body mass index >= 24) was 5.84%, which was obviously higher than that in normal population (P < 0.01). In anti-oxidants group, the probability of HDP in women with high-risk factors was 3.81%, which was obviously lower than that in control group with high risk factors at 7.14% (P < 0.01). (4) In control group, the morbidity of HDP in women with family HDP history (especially with sisters'), heavy physical labor, middle school and below, age >= 35 was: 50.00%, 15.22%, 6.33%, 26.28% and 5.75%, respectively, and that in anti-oxidants group was 0, 7.69%, 3.74%, 9.27% and 2.67%, respectively, which was obviously lower than that in control group. CONCLUSIONS: The high-risk factors prone to induce HDP included: family history of HDP, heavy physical labor, low education level, aging and obesity. No impressive effect of anti-oxidants application was found in preventing HDP in general population but the remedy demonstrated positive effect on preventing HDP in pregnant women with high-risk factors. PMID- 21034628 TI - Out-of-the-bag intraocular lens dislocation: outcomes of posterior chamber intraocular lens exchange, risk factors, and prevention. AB - BACKGROUND: Dislocation of posterior chamber intraocular lens is one of the most common complications of intraocular lens implantation. Lens exchange is an effective solution to this unsatisfactory status. This study was conducted to analyze the possible predisposing factors for out-of-the-bag posterior chamber intraocular lens dislocation and to study the outcomes of lens exchange surgery. METHODS: Thirty-six consecutive patients (36 eyes) with out-of-the-bag intraocular lens dislocation who underwent posterior chamber intraocular lens exchange in Zhongshan Ophthalmic Center of Sun Yat-sen University (Guangdong, China) from January 2003 to October 2009 were included. A 6-month follow-up was completed. The causes for out-of-the-bag intraocular lens dislocation and visual outcomes of posterior chamber intraocular lens exchange were analyzed. The out-of the-bag intraocular lens dislocation was diagnosed on the basis of the findings from slit-lamp microscope and B-ultrasound. The dislocated intraocular lens was explanted. Reimplantation of a new posterior chamber intraocular lens was performed in each case using standardized surgical procedures. RESULTS: In this study, a total of thirty-six consecutive patients (36 eyes) with out-of-the-bag intraocular lens dislocation underwent posterior chamber intraocular lens exchange surgery. Causes for out-of-the-bag intraocular lens dislocation included posterior capsule rupture during the initial cataract extraction procedure (23 eyes, 63.8%), trauma (5 eyes, 13.9%),neodymium-doped yttrium aluminium garnet (Nd:YAG) laser-induced dislocation (2 eyes, 5.6%), the status after vitrectomy (2 eyes, 5.6%) and unidentifiable etiology (4 eyes, 11.1%). Symptoms of these patients mainly included decrease in visual acuity (17 cases, 47.2%), blurred vision (16 cases, 44.4%), glare (1 case, 2.8%), diplopia (1 case, 2.8%), and halo (1 case, 2.8%). Intraocular lens dislocation into the posterior vitreous cavity (29 eyes, 80.5%), anterior chamber (1 eye, 2.8%) and anterior vitreous cavity (6 eyes, 16.7%) was found in this series. The foldable intraocular lenses (acrylic or silicone) were explanted from 27 eyes (75%) and rigid intraocular lenses (poly methyl methacrylate, PMMA) from 9 eyes (25%). The most common explanted intraocular lens material was single-piece acrylic (13 pieces, 36.1%), followed by 3-piece acrylic (9 pieces, 25%), single-piece PMMA (9 pieces, 25%), and 3 piece silicone (5 pieces, 13.9%). Uncorrected visual acuity postoperatively improved in 29 eyes (81%), unchanged in 4 eyes (11%), and worsened in 3 eyes (8%) in comparison to that before exchange operation (P = 0.006). Best corrected visual acuity tended to improve, but the improvement was not significant (P = 0.206). Complications related to lens exchange surgery were mainly intraocular lens redislocation (1 eye), retinal detachment (1 eye), vitreous hemorrhage (1 eye), and cystoid macular edema (1 eye). CONCLUSIONS: Out-of-the-bag intraocular lens dislocation was mainly caused by posterior capsule rupture during the initial cataract extraction procedure and the foldable lens was the most common dislocated intraocular lens. In most cases, posterior chamber intraocular lens exchange surgery could provide satisfied final visual outcomes. PMID- 21034629 TI - Emergence of Klebsiella pneumoniae carbapenemase-producing Proteus mirabilis in Hangzhou, China. AB - BACKGROUND: Carbapenems are used to treat severe infections caused by multi-drug resistant organisms, however, the emergence of carbapenem-resistant bacterial isolates is becoming an increasing therapeutic challenge. Since the first Klebsiella (K.) pneumoniae carbapenemase (KPC)-producing K. pneumoniae was reported in 2001, KPC-producing isolates have been found increasingly, specially in Enterobacteriaceae. The aim of this study was to characterize the mechanisms of a carbapenem-resistant Proteus (P.) mirabilis. METHODS: A carbapenem-resistant P. mirabilis isolate was recovered from pleural drainage fluid of a patient admitted to surgical intensive care unit. Antimicrobial susceptibility testing of the isolate was performed by disk diffusion according to Clinical and Laboratory Standards Institute guidelines, and subsequent minimal inhibitory concentrations were determined with the E-test. Amplification of the bla(KPC) gene generated a positive band and the PCR products were sequenced subsequently. The plasmid of the isolate was extracted and was successfully transformed into Escherichia (E.) coli DH5alpha. RESULTS: The P. mirabilis isolate was resistant to all detected antimicrobial agents except tigecycline. KPC-2 was confirmed by DNA sequence analysis. The transformant E. coli was resistant to carbapenems. Further study demonstrated that upstream and downstream regions of bla(KPC-2) were identical to that observed in K. pneumoniae submitted to GenBank from China in 2007. CONCLUSION: Carbapenem resistance in the P. mirabilis isolate in this study is mainly due to production of KPC-2. PMID- 21034631 TI - A new plastic model of endoscopic technique training for endonasal transsphenoidal pituitary surgery. AB - BACKGROUND: Endoscopic transsphenoidal approach is a minimally invasive surgical technique for the removal of sellar and parasellar lesions, which has been progressively accepted by neurosurgeons. However, frustration is often expressed by neurosurgeons when first attempting endoscopic endonasal pituitary surgery. To overcome the learning curve from microscope to endoscope in a smooth way, a new human nasal model has been developed. The present study assessed this new model of the human paranasal sinuses for endonasal surgery training, particularly for endonasal pituitary surgery training. METHODS: The procedure for endonasal transsphenoidal endoscopy was performed using this model. Three approaches were used to observe the endonasal structures and sphenoidal sinus: paraseptal; middle turbinectomy; and middle meatal. Attempts were made to identify anatomical landmarks in the nasal cavity and sphenoidal sinus. Model landmarks were compared with those in a cadaver and a real patient. RESULTS: This model precisely reproduced nasal bone structure. Compared with cadavers and living bodies, intranasal structures displayed very good color and texture, providing a close facsimile of the operative environment, and good morphology, with similar hardness and tactile feel on resection. All intranasal anatomical landmarks were easily identified, including choanae, inferior, middle and superior turbinates, and even the natural ostium of the sphenoidal sinus. CONCLUSION: This human nasal model is very useful for training neurosurgeons in endoscopic endonasal transsphenoidal pituitary surgery, but typical anatomical landmarks in the posterior wall of the sphenoidal sinus in this model should be improved. PMID- 21034630 TI - Drug-resistant genes carried by Acinetobacter baumanii isolated from patients with lower respiratory tract infection. AB - BACKGROUND: Acinetobacter baumanii (A. baumanii ) remains an important microbial pathogen resulting in nosocomial acquired infections with significant morbidity and mortality. The mechanism by which nosocomial bacteria, like A. baumanii, attain multidrug resistance to antibiotics is of considerable interest. The aim in this study was to investigate the spread status of antibiotic resistance genes, such as multiple beta-lactamase genes and aminoglycoside-modifying enzyme genes, from A. baumanii strains isolated from patients with lower respiratory tract infections (LRTIs). METHODS: Two thousand six hundred and ninety-eight sputum or the bronchoalveolar lavage samples from inpatients with LRTIs were collected in 21 hospitals in the mainland of China from November 2007 to February 2009. All samples were routinely inoculated. The isolated bacterial strains and their susceptibility were analyzed via VITEK-2 expert system. Several kinds of antibiotic resistant genes were further differentiated via polymerase chain reaction and sequencing methods. RESULTS: Totally, 39 A. baumanii strains were isolated from 2698 sputum or bronchoalveolar lavage samples. There was not only a high resistant rate of the isolated A. baumanii strains to ampicillin and first- and second-generation cephalosporins (94.87%, 100% and 97.44%, respectively), but also to the third-generation cephalosporins (ceftriaxone at 92.31%, ceftazidine at 51.28%) and imipenem (43.59%) as well. The lowest antibiotic resistance rate of 20.51% was found to amikacin. The OXA-23 gene was identified in 17 strains of A. baumanii, and the AmpC gene in 23 strains. The TEM-1 gene was carried in 15 strains. PER-1 and SHV-2 genes were detected in two different strains. Aminoglycoside-modifying enzyme gene aac-3-Ia was found in 23 strains, and the aac-6'-Ib gene in 19 strains. aac-3-Ia and aac-6'-Ib genes hibernated in three A. baumanii strains that showed no drug-resistant phenotype. CONCLUSIONS: A. baumanii can carry multiple drug-resistant genes at the same time and result in multi-drug resistance. Aminoglycoside-modifying enzyme genes could be hibernating in aminoglycoside sensitive strains without expressing their phenotype. PMID- 21034632 TI - Establishment of intramedullary spinal cord glioma model in rats. AB - BACKGROUND: Treating intramedullary spinal cord gliomas is a big challenge because of limited options, high recurrence rate and poor prognosis. An intramedullary glioma model is prerequisite for testing new treatments. This paper describes the establishment of a rodent intramedullary glioma model and presents functional progression, neuroimaging and histopathological characterization of the tumour model. METHODS: Fischer344 rats (n = 24) were randomized into two groups. Group 1 (n = 16) received a 5 ul intramedullary implantation of 9L gliosarcomal (105) cells. Group 2 (n = 8) received a 5 ul intramedullary injection of Dulbecco's modified Eagle medium. The rats were anesthetized, the spinous process of the T10 vertebra and the ligamentum flavum were removed to expose the T10-11 intervertebral space and an intramedullary injection was conducted into the spinal cord. The rats were evaluated preoperatively and daily postoperatively for neurological deficits using the Basso, Beattie and Bresnahan scale. High resolution magnetic resonance images were acquired preoperatively and weekly postoperatively. When score equal to 0, rats were sacrificed for histopathological examination. RESULTS: Rats implanted with 9L gliosarcoma cells had a statistically significant median onset of hind limb paraplegia at (16.0 +/- 0.4) days, compared with rats in the control group in which neurological deficits were absent. Imaging and pathological cross sections confirmed intramedullary 9L gliosarcoma invading the spinal cord. Rats in the control group showed no significant functional, radiological or histopathological findings of tumour. CONCLUSIONS: Rats implanted with 9L cells regularly develop paraplegia in a reliable and reproducible manner. The progression of neurological deficits, neuroimaging and histopathological characteristics of intramedullary spinal cord gliomas in rats is comparable with the behaviour of infiltrative intramedullary spinal cord gliomas in patients. PMID- 21034633 TI - Transplantation of 5-azacytidine treated cardiac fibroblasts improves cardiac function of infarct hearts in rats. AB - BACKGROUND: Cellular cardiomyoplasty by transplantation of various cell types has been investigated as potential treatments for the improvement of cardiac function after myocardial injury. A major barrier for the clinical application of cell transplantation is obtaining sufficiently large quantities of suitable cells. Allogeneic cellular cardiomyoplasty may provide an alternative source of abundant, transplantable, myogenic cells by in vitro manipulation of cardiac fibroblasts using chemicals including 5-azacytidine. This study evaluated cardiomyogenic differentiation of cardiac fibroblasts, their survival in myocardial scar tissue, and the effect of the implanted cells on heart function. METHODS: Primary cardiac fibroblasts from neonatal rats were treated with 5 azacytidine (10 umol/L) or control. Treatment of 5-azacytidine caused myogenic differentiation of cultured cardiac fibroblasts, as defined by elongation and fusion into multinucleated myotubes with sarcomeric structures as identified by electron microscopy, and positive immunostaining for cardiac specific proteins, troponin I and beta-myosin heavy chain (beta-MHC) and the gap junction protein connexin 43. The myogenic cells (1.0 * 106) were transplanted into the infarcted myocardium 2 weeks after coronary artery occlusion. RESULTS: By 1 month after transplantation, the converted fibroblasts gave rise to a cluster of cardiac-like muscle cells that in the hearts occupied a large part of the scar with positive immunostaining for the myogenic proteins troponin I and beta-MHC. Engrafted cells also expressed the gap junction protein connexin 43 in a disorganized manner. There was no positive staining in the control hearts treated with injections of culture medium. Heart function was evaluated at 6 weeks after myocardial injury with echocardiographic and hemodynamic measurements. Improvement in cardiac function was seen in the hearts transplanted with the 5-azacytidine-treated cardiac fibroblasts which was absent in the hearts treated with control. CONCLUSION: The 5-azacytidine has a unique capacity to induce myogenesis in cardiac fibroblasts in vitro and transplantation of cardiac-like muscle cells into ventricular scar tissue improves myocardial function. PMID- 21034634 TI - Pregnancy estrogen drives the changes of T-lymphocyte subsets and cytokines and prolongs the survival of H-Y skin graft in murine model. AB - BACKGROUND: Estrogen as well as CD4(+)Foxp3(+) regulatory T cells were shown to have a protective role not only in maintaining maternal-fetal tolerance but also against autoimmune diseases. We aimed to investigate whether the pregnancy levels of estrogen are enough to induce transplant tolerance as to maintain fetal maternal tolerance. METHODS: We established H-Y skin graft transplantation in C57BL/6 ovariectomized mice that reconstituted with estrogen. Subsequently, consecutive daily estrogen injection was administrated. Tregs and the cytokines in the peripheral blood were detected by flow cytometry and ELISA pre- and post transplant. RESULTS: The results indicated that pregnancy levels of estrogen could promote Tregs in secondary lymphoid organs and peripheral blood (P < 0.05) but not thymus (P > 0.05). The estrogen-treated recipients accepted H-Y skin grafts for more than 35 days (median survival time (MST): (44.0 +/- 1.2) days) compared with estrogen-untreated mice (MST: (23.0 +/- 1.6) days) (P < 0.05). It was also observed that estrogen up-regulated the expression of Foxp3, but did not affect CD3(+)CD8(+) effector T-cells in non-transplant mice. While in the presence of H-Y antigens, the expression of Foxp3 was more significant and CD3(+)CD8(+) effector T cells were decreased significantly (P < 0.05). Meanwhile, the up-regulated IL-10 and IL-4, and down-regulated IFN-gamma could be observed (P < 0.05). CONCLUSIONS: Pregnancy levels of estrogen may promote the conversion of peripheral Tregs in secondary lymphoid organs, but show no effect on the natural Tregs production, differentiation and maturity in central lymphoid organs. Furthermore, pregnancy levels of estrogen could significantly prolong the survivals of H-Y skin grafts by the expansion of Tregs, suppression of CD3(+)CD8(+) effector T-cells and immune shift towards Th2 cytokines. PMID- 21034635 TI - Preventive effect of ulinastatin and gabexate mesylate on post-endoscopic retrograde cholangiopancreatography pancreatitis. AB - BACKGROUND: Post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) is regarded as one of the worrisome complications of endoscopic retrograde cholangiopancreatography (ERCP). Results of randomized controlled trials evaluating the preventive effect of ulinastatin and gabexate mesylate (GM) on PEP are contradictory. The present study was designed to evaluate the prophylactic effect of ulinastatin and GM on PEP with meta-analyses of randomized controlled trials (RCTs). METHODS: Five electronic databases were searched for RCTs evaluating the preventive effect of ulinastatin and GM on PEP. Summary effects were assessed with the methods recommended by the Cochrane Collaboration. RESULTS: Twelve studies involving 5105 participants were included in our meta analyses. Administration of ulinastatin decreased the incidence of PEP only at sufficient doses (OR, 0.39; 95%CI, 0.19 to 0.81; P = 0.01). Number needed to treat (NNT) was 6. And administration of ulinastatin also reduced the incidence of post-ERCP hyperamylasemia (PEHA) (OR, 0.40; 95%CI, 0.28 to 0.58; P < 0.000 01). Slow infusion of high-dose GM was effective for PEP prevention (OR, 0.44; 95%CI, 0.25 to 0.79; P = 0.006), and rapid infusion of low-dose GM also showed efficacy for PEP prophylaxis (OR, 0.37; 95%CI, 0.20 to 0.69; P = 0.002). NNT was 7 and 6 respectively. However, administration of GM at low doses and by slow infusions was ineffective (OR, 0.99; 95%CI, 0.64 to 1.55; P = 0.98). Administration of GM had the tendency to reduce PEHA rate, but not to a statistical significance (OR, 0.86; 95%CI, 0.73 to 1.01; P = 0.06). When low quality studies were excluded, the meta-analysis with two high-quality studies indicated that ulinastatin did not reduce the rate of PEP (OR, 0.63; 95%CI, 0.32 to 1.26; P = 0.19) and PEHA incidence (OR, 0.80; 95%CI, 0.31 to 2.07; P = 0.64). The meta-analysis with six high-quality studies showed that GM administration decreased PEP incidence (OR, 0.52; 95%CI, 0.29 to 0.91; P = 0.02), while was not efficacious for PEHA prevention (OR, 0.88; 95%CI, 0.74 to 1.04; P = 0.12). CONCLUSIONS: Ulinastatin and GM may be of value for the prophylaxis of PEP. GM should be administered at high doses and by rapid infusions. And the doses of ulinastatin should be sufficient. However, the conclusions are not overwhelming. More large-sample size and high-quality RCTs are still needed to elucidate whether administrations of the two drugs really have prophylactic effect on PEP. PMID- 21034636 TI - HOX genes in the skin. PMID- 21034637 TI - Late intra-atrial reentrant tachycardia would be prevented by ablation of right atrial potential isthmuses during the surgical operation for congenital heart disease. PMID- 21034638 TI - Endovascular embolization for gastrointestinal bleeding caused by splenic arteriovenous fistula. PMID- 21034639 TI - Single incision laparoscopic liver resection: a case report. PMID- 21034640 TI - Titanium internal fixation system used for sternum reconstruction after resection of chondrosarcoma. PMID- 21034641 TI - Delayed type IIIb endoleak using AnacondaTM stent graft in abdominal aortic aneurysm repair. PMID- 21034642 TI - Future prospects of pediatric cardiology in China. PMID- 21034643 TI - Epidemiologic features of Kawasaki disease in Shanghai from 2003 through 2007. AB - BACKGROUND: The epidemiologic pictures of Kawasaki disease (KD) in Shanghai from 1998 through 2002 were reported, while the current status of KD in the following five years remains unknown. METHODS: A questionnaire form and diagnostic guidelines for KD were sent to 50 hospitals providing pediatric medical care in Shanghai, China. All patients with KD diagnosed during January 2003 through December 2007 were recruited. RESULTS: In total, 1187 cases of KD were enrolled. The incidence of KD was 36.78 to 53.28 (mean 46.32 +/- 6.51) per 100 000 children under the age of 5 years between 2003 and 2007, which was higher than the year from 1998 to 2002 of (27.32 +/- 7.11) per 100 000, (t = 4.406, P = 0.002). Ages at onset ranged from 12 days to 13.6 years (median 1.8 years). It occurred more frequently in summer and spring. Coronary arterial lesions (CAL), defined as ectasia or aneurysm, accounted for 19.8% (232 cases). Flattened or inverted T wave was the most frequent finding (194 cases, 20.5%) by electrocardiogram. Intravenous gamma-globulin was administrated to 1028 cases (86.6%). The occurrence of CAL seemed less frequent in the patients received gamma-globulin from day 5 to day 9 after the onset with the regimen of 1000 mg/kg once or 1000 mg/kg twice. CONCLUSIONS: The incidence of KD was increasing in Shanghai. Treatment with intravenous gamma-globulin from day 5 to day 9 after the onset with the regimen of 1000 mg/kg once or 1000 mg/kg twice resulted in less coronary sequelae. PMID- 21034644 TI - Cost-effectiveness of diagnostic approaches to vasovagal syncope. AB - BACKGROUND: Syncope is a common clinical problem with multiple causes. Vasovagal syncope (VVS) is by far the most frequent cause of syncope in children and adolescents. The traditional diagnostic approach to VVS of children and adolescents is based on a series of tests to exclude all other causes, which is complex and time and medical resource consuming. Attempts have been made to develop a new cost-effective diagnostic approach to avoid these problems. This study aimed to compare the economic effectiveness and diagnostic value of the traditional diagnostic approach to VVS of children with a new diagnostic approach. METHODS: One hundred and eighteen children diagnosed as VVS were divided into two groups according to the different diagnostic approaches. The diagnostic value of the two diagnostic approaches was then analyzed. Meanwhile, the costs of hospitalization, diagnostic testing and hospital stay were determined. Data were evaluated by the cost-minimization analysis. RESULTS: The diagnostic value of the new diagnostic approach was similar to that of the traditional diagnostic approach (56.57% vs. 53.91%, P = 0.697). However, the cost of hospitalization per patient by the new diagnostic approach was (1507.08 +/- 144.63) Yuan (RMB) which was less than that of the traditional diagnostic approach (2603.64 +/- 208.19) Yuan. The costs of diagnostic tests per patient by the new diagnostic approach was (1256.04 +/- 109.14) Yuan and by the traditional approach (2175.22 +/- 153.32) Yuan. CONCLUSION: Compared to the traditional diagnostic approach to diagnose VVS in children and adolescents, the new diagnostic approach is of a good economic value, and it should be popularized in clinical practice. PMID- 21034645 TI - Clinical characteristics, diagnosis and management of respiratory distress syndrome in full-term neonates. AB - BACKGROUND: Respiratory distress syndrome (RDS) is one of the most common causes of neonatal respiratory failure and neonatal death, however, its clinical characteristics are very different from premature RDS, and these characteristics have not been well documented as yet. This study was to investigate the pathogenesis, clinical characteristics and management strategies of RDS in full term neonates, with the aim of developing a working protocol for improving the outcome in full-term neonates with RDS. METHODS: A total of 125 full-term infants with RDS were enrolled in this study. Their clinical and laboratory data were collected for analyzing the characteristics of full-term neonatal RDS. RESULTS: (1) The 125 cases included 94 male and 31 female infants, vaginal delivery occurred in 80 cases and cesarean section in 45 cases. (2) The onset time of RDS was (3.11 +/- 3.59) hours after birth. (3) The possible reasons included severe perinatal infections in 63 patients, elective cesarean section in 34 cases, severe birth asphyxia in 12 patients, meconium aspiration syndrome in 9 patients, pulmonary hemorrhage in 4 patients and maternal diabetes in 3 patients. (4) Complications included multiple organ system failure (MOSF) in 49 patients, persistent pulmonary hypertension of newborn (PPHN) in 25 patients, acute renal failure in 18 patients, severe hyperkalemia in 25 patients, severe metabolic acidosis in 6 cases, severe myocardial injury in 9 cases, pulmonary hemorrhage in 3 cases, disseminated intravascular coagulation in 14 patients and shock in 12 patients. (5) Four patients died, the mortality was therefore 3.2% with the main cause of septicemia complicating of MOSF, but their prognosis was improved while comprehensive treatment measures including early mechanical ventilation and broad spectrum antibiotics were taken into account. CONCLUSIONS: RDS is not an uncommon disease in full-term infants and is associated with a higher mortality, its clinical characteristics are very different from premature RDS, and its onset is earlier and is more likely to develop into PPHN and/or MOSF. The main cause of death is severe infection complicating of MOSF and most patients require prolonged mechanical ventilation. Comprehensive management strategies will help to improve patient's prognosis. PMID- 21034646 TI - Pulmonary artery perfusion with HTK solution prevents lung injury in infants after cardiopulmonary bypass. AB - BACKGROUND: Pulmonary artery perfusion during cardiopulmonary bypass (CPB) is a novel adjunctive method, which can minimize the lung ischemic-reperfusion injury and inflammatory response. This study evaluated the protective effect of pulmonary perfusion with hypothermic HTK solution in corrections of congenital heart defects with pulmonary hypertension. METHODS: Between June 2009 and December 2009, 24 consecutive infants with congenital heart defects and pulmonary hypertension were randomly divided into perfused group (n = 12) and control group (n = 12). Oxygen index, alveolar-arterial O2 gradient, serum levels of malondialchehyche (MDA), interleukin (IL)-6, -8, -10, soluble intercellular adhesion molecule-1 (sICAM-1), and P-selectin were measured before commencement and serially for 48 hours after termination of bypass. RESULTS: Oxygenation values were better preserved in the perfused group than in the control group. The serum levels of IL-6 increased immediately after CPB in both groups and returned to baseline at 48 hours after CPB,but it was restored faster and earlier in the perfused group. The serum levels of IL-8, sICAM-1, and MDA remained at baseline at each point after CPB in the perfused group and elevated significantly immediately after CPB in the control group, except for sICAM-1. The serum level of IL-10 increased immediately after CPB and decreased to baseline at 48 hours after CPB in both groups, but the IL-10 level in the perfused group was significantly higher than in the control group at 12 hours after CPB. The serum P selectin levels in the control group immediately after CPB were significantly higher than prebypass levels. Moreover, there were no significant differences in postoperative clinical characters, except for the intubated time. CONCLUSION: In infants with congenital heart defects, pulmonary perfusion with hypothermic HTK solution during cardiopulmonary bypass could ameliorate lung function and reduce the inflammatory response. PMID- 21034647 TI - Clinical features of initial cases of 2009 pandemic influenza A (H1N1) in Macau, China. AB - BACKGROUND: The first case of pandemic influenza A (H1N1) virus infection in Macau Special Administrative Region (SAR) of the People's Republic of China was documented on June 18, 2009. Subsequently, persons with suspected infection or of contact with suspected cases received screening. All the confirmed cases were hospitalized and treated with oseltamivir. Their clinical features were observed. This may help for better management for later patients and be of benefit to the government of Macau SAR to adjust its strategy to combat the pandemic influenza A (H1N1) virus infection more efficiently. METHODS: From June to July 2009, the initial 72 cases of influenza A (H1N1) in Macau were hospitalized in Common Hospital Centre S. Januario (CHCSJ). The infection was confirmed by real-time reverse-transcriptase polymerase chain reaction (RT-PCR). The clinical features of the disease were closely observed and documented. Oseltamivir was given to all patients within 48 hours after the onset of disease and maintained for 5 days. RESULTS: The mean age of the 72 patients was 21 years old. Forty of them were men and 32 were women. The median incubation of the virus was 2 days (1 to 7 days). The most common symptoms were fever (97.2%) and cough (77.8%). The rate of gastrointestinal symptoms including nausea, vomiting, and diarrhea was 2.8%. Fever typically lasted for 3 days (1 to 9 days). The median time from the onset to positive results of real-time RT-PCR was 6 days (3 to 13 days). After treatment with oseltamivir, most patients became afebrile within 48 hours. Only one aged patient with a history of glaucoma and hypothyroidism was found to have lung infiltration on chest X-ray. CONCLUSIONS: The initial cases of pandemic influenza A (H1N1) virus infection in Macau SAR showed that most of the infected persons had a mild course. The virus could be detected by real-time RT-PCR within a median of 6 days from the onset. Oseltamivir was effective. PMID- 21034648 TI - Proliferation, migration and apoptosis activities of endothelial progenitor cells in acute coronary syndrome. AB - BACKGROUND: There are numerous articles on the endothelial progenitor cells (EPCs) in different disease conditions. However, the functional properties of EPCs in acute coronary syndrome (ACS) are still uncertain. Here we aimed to study the number and functions of EPCs in ACS patients. METHODS: Patients were enrolled with admitted ACS (n = 25) and another 25 gender-, age-, atherosclerotic risk factors-matched stable coronary artery disease (CAD) controls. EPCs were defined as CD34(+)/CD133(+)/VEGFR-2(+) and quantified by flow cytometry. Moreover, functional properties of EPCs including colony-forming unit (CFU), proliferation, migration as well as apoptosis were evaluated and compared between the two groups. Plasma matrix metalloproteinase-9 (MMP-9) was detected in all patients as well. RESULTS: The two groups had similar medication and clinical characteristics on admission. The EPCs in ACS patients were more than 2.6 times that in stable CAD subjects (15.6 +/- 2.7 vs. 6.0 +/- 0.8/100 000 events, P < 0.01). CFU was not statistically different between the two groups (10.8 +/- 2.9 vs. 8.2 +/- 1.8, number/well, P > 0.05). Furthermore, EPCs isolated from ACS patients were significantly impaired in their proliferation (0.498 +/- 0.035 vs. 0.895 +/- 0.067, OD value, P < 0.01) and migration capacity (20.5 +/- 3.4 vs. 30.7 +/- 4.3, number/well, P < 0.01) compared with controls. Moreover, the apoptosis cell in cultured EPCs was drastically increased in ACS group ((18.3 +/- 2.1)% vs. (7.8 +/ 0.4)%, P < 0.01). CONCLUSIONS: Patients with ACS exhibited apparently increased circulating EPCs as well as cultured apoptosis percentage together with a remarkable impairment of proliferation and migration activities compared with stable CAD subjects. PMID- 21034649 TI - Fifty-eight cases of ocular ischemic diseases caused by carotid artery stenosis. AB - BACKGROUND: The blood supply to the eye comes from the retinal central vascular system of the ophthalmic artery and the ciliary vascular system. The ophthalmic artery stems from the ipsilateral internal carotid artery. If occlusion or stenosis occurs in the carotid artery, the blood perfusion to the ophthalmic artery becomes insufficient, leading to signs and symptoms of anterior and posterior ocular ischemia. The objective of this study was to evaluate the clinical characteristics and risk factors of ocular ischemic diseases caused by carotid artery stenosis. METHODS: This study was a retrospective review of 145 patients with carotid artery stenosis. Fifty-eight patients who had symptoms of ocular ischemic disease caused by carotid artery stenosis formed group A and the other 87 patients who only had carotid artery stenosis formed group B. We analyzed the causes and course of disease, and relative risk factors, by comparing the two groups. RESULTS: The degree of carotid artery stenosis in group A was higher than that in group B. And group A had a greater decrease of ophthalmic artery flow. Male, hypertension, hyperlipidemia, and smoking were significantly related to carotid artery stenosis. Amaurosis fugax was the most common ocular symptom in group A. The ocular ischemic diseases mainly included ischemic optic neuropathy, central/branch retinal artery occlusion, ophthalmoplegia externa, and ocular ischemic syndrome. CONCLUSIONS: Carotid artery stenosis correlates with ocular ischemic diseases. Ophthalmologists must observe for ocular symptoms, which were the onset symptoms in some patients. PMID- 21034650 TI - Total knee arthroplasty using computer assisted navigation in patients with severe valgus deformity of the knee. AB - BACKGROUND: Severe valgus deformity often has bone defect and laxity of the medial ligamentous, and total knee arthroplasty in severe valgus knee is, in most cases, more challenging for surgeons. The usefulness of a computer assisted navigation system in reestablishing the mechanical axis has been well established. Hence, the interest for surgeons is how the navigation system makes the procedure of total knee arthroplasty with severe valgus knee easier. METHODS: From June 2006 to March 2008 in Department of Joint Surgery, Shanghai Sixth People's Hospital, 6 patients (7 knees) with severe valgus knee underwent total knee arthroplasty using the Stryker Navigation system, which is an active wireless and imageless system. All the patients were followed up for 12 to 18 months after surgery. The X-ray radiographs for whole limbs were obtained on all patients to determine preoperative and postoperative alignments. RESULTS: A primary, posterior stabilized prosthesis was utilized in all cases. The average preoperative overall mechanical axis of the seven knees was 19.6 degrees +/- 4.6 degrees of valgus (range 16 degrees to 29 degrees ), and the average postoperative mechanical axis was 0.4 degrees +/- 0.7 degrees (range 0.8 degrees varus to 1.4 degrees valgus). CONCLUSIONS: The navigation system is a very effective and useful tool for accurate intraoperative restoration of alignment in the face of significant deformity with valgus knee. To prevent component malposition, we did not reduce the knee before solidification of bone cement but controlled alignment using the navigation system up to implantation of the final component. PMID- 21034651 TI - Complications of the locking plate for displaced proximal humeral fractures. AB - BACKGROUND: Although the locking plate has become popular for treating displaced proximal humeral fractures in recent years, the complications of this method are still underestimated. We tried to evaluate the factors that have an influence on the complications experienced after proximal humeral fractures fixed by locking plates and compare the results from patients having complications with those having no complications. METHODS: From September 2004 to September 2007, 92 out of 111 displaced proximal humeral fractures treated by open reduction and internal fixation with a locking plate were available for follow-up, with an average time of 15.2 months (12 - 36 months). The range of motion, Visual Analog Score (VAS) for pain, American Shoulder and Elbow Surgeons' Form (ASES), Constant Murley, University of California-Los Angles scoring system (UCLA) score, and Simple Shoulder Test (SST) for function evaluation was all recorded at the latest follow-up. The results from patients with complications were evaluated according to the indices listed above and compared with those patients without any complications. RESULTS: There were 17 patients with complications, an 18.5% complication rate. Among them, the forward flexion, external rotation and internal rotation were 139.1 degrees +/- 24.3 degrees , 24.1 degrees +/- 19.6 degrees , and up to T10 level on average. The mean VAS score was 1.0 +/- 1.1, the ASES score was 82.9 +/- 13.8, the Constant 82.1 +/- 11.8, the UCLA 28.5 +/- 4.1 and the mean SST 9.5 on average. There was no significant difference of complication rate among different age, sex, and injured side, fresh or delayed fracture, combined with other injury or not groups. Compared with the group without complications, patients with complications showed significantly less external rotation and lower Constant-Murley and UCLA functional scores (P < 0.05). A significant difference in results was seen between patients with complications and those without complications. CONCLUSION: The indication control and appropriate surgical technique were important while performing the locking plate fixation for proximal humeral fractures. PMID- 21034652 TI - Linker for activation of T cells contributes to airway inflammation in an asthmatic mouse model. AB - BACKGROUND: Allergic asthma is associated with airway inflammation and hyperresponsiveness caused by dysregulated production of cytokines secreted by allergen-specific helper T-type 2 (Th2) cells. The linker for activation of T cells (LAT) is a membrane-associated adaptor protein, which has been shown to take part in regulating T cell receptor (TCR) signaling and T cell homeostasis. In this study, we established an asthmatic mouse model to examine the changes in LAT levels during allergic airway disease and the effects of LAT transgenic expression on airway inflammation. METHODS: T cells from mouse lung tissues were isolated from allergen challenged (ovalbumin (OVA)) and control mice, and the purity of these isolated T cells was examined by fluorescence-activated cell sorter (FACS). Semi-quantitative RT-PCR and Western blotting were used to detect the expression of the LAT gene and LAT protein, respectively. After an intranasally administered mixture of pCMV-HA-LAT plasmid and Lipofectamine 2000, 24 hours before and 72 hours after allergen challenge, the BALF cell count and the differential cytologies were studied. In addition, IL-4 and IFN-gamma levels in the BALF were determined by ELISA, and pathological changes in lung tissues were observed. RESULTS: LAT protein and mRNA expression were decreased in lung T cells in a mouse model of allergen-induced airway disease. After intranasal administration of pCMV-HA-LAT, histopathological examination of the lungs showed that intervention with LAT overexpression prevented mice from developing airway inflammation, and the number of total cells, eosinophils, neutrophils, and lymphocytes in the BALF was reduced significantly compared with the OVA sensitized and challenged group. In addition, the Th2 cytokine IL-4 decreased, while the Th1 cytokine IFN-gamma increased compared to the OVA sensitized and challenged group or the OVA sensitized group plus pCMV-HA treatment. CONCLUSION: This study demonstrates that LAT might effectively diminish Th2 cytokine responses, lung histopathological changes and lung inflammation to allergen challenge in a model of experimentally induced asthma. PMID- 21034653 TI - Valproic acid attenuates the multiple-organ dysfunction in a rat model of septic shock. AB - BACKGROUND: Valproic acid (VPA) improves early survival and organ function in a highly lethal poly-trauma and hemorrhagic shock model or other severe insults. We assessed whether VPA could improve organ function in a rat model of septic shock and illustrated the possible mechanisms. METHODS: Forty Sprague-Dawley rats were randomly assigned to four groups (n = 10): control group, VPA group, LPS group, and LPS + VPA group. Lipopolysaccharide (LPS) (10 mg/kg) was injected intravenously to replicate the experimental model of septic shock. Rats were treated with VPA (300 mg/kg, i.v.) or saline. Six hours after LPS injection, blood was sampled for gas analysis, measurement of serum alanine aminotransferase, aspartate aminotransferase, urine nitrogen, creatinine and tumor necrosis factor-alpha. Lung, liver and kidney were collected for histopathological assessment. In addition, myeloperoxidase activity and tumor necrosis factor-a in pulmonary tissue were measured. Acetylation of histone H3 in lung was also evaluated by Western blotting. RESULTS: LPS resulted in a significant decrease in PaO2, which was increased by VPA administration followed LPS injection. In addition, LPS also induced an increase in the serum levels of alanine aminotransferase, aspartate aminotransferase, urine nitrogen, creatinine, and tumor necrosis factor-alpha. However, these increases were attenuated in the LPS + VPA group. The lungs, liver and kidneys from the LPS group were significantly damaged compared with the control group. However, the damage was attenuated in the LPS + VPA group. Myeloperoxidase activity and tumor necrosis factor-alpha levels in pulmonary tissue increased significantly in the LPS group compared with the control group. These increases were significantly inhibited in the LPS + VPA group. Acetylation of histone H3 in lung tissue in the LPS group was inhibited compared with the control. However, the level of acetylation of histone H3 in the LPS + VPA group was markedly elevated in contrast to the LPS group. CONCLUSIONS: Treatment with VPA can attenuate multiple organ damage caused by LPS induced septic shock. Our data also suggest that the beneficial effects are in part due to the decrease in inflammatory cytokines and restoration of normal acetylation homeostasis. PMID- 21034654 TI - Effects of pentoxifylline on Wnt/beta-catenin signaling in mice chronically exposed to cigarette smoke. AB - BACKGROUND: Previous discovery that long-term administration of pentoxifylline (PTX) to mice chronically exposed to smoke led to the development of pulmonary fibrosis rather than emphysema initiated our curiosity on whether the Wnt/beta catenin pathway, a set of signaling proteins essential to organ development and lung morphogenesis in particular were activated in the pathogenesis of pulmonary fibrosis. METHODS: Male BALB/c mice were randomized into four study groups: Group Sm, smoke exposure and taken regular forage; Group PTX, no smoke but taken PTX rich forage; Group Sm + PTX, smoke exposure and taken PTX-rich forage; Group control: shamed smoke exposure and taken regular forage. Animals were sacrificed at day 120. Morphometry of the lung sections and the expressions of TGF-beta(1), hydroxyproline, beta-catenin, cyclin D1, T cell factor 1 (Tcf-1) and lymphoid enhancer factor 1 (Lef-1) mRNA, etc, in the lung homogenate or in situ were qualitatively or quantitatively analyzed. RESULTS: As expected, smoke exposure along with PTX administration for 120 days, lungs of the mice progressed to be a fibrosis-like phenotype, with elevated fibrosis score (3.9 +/- 1.1 vs. 1.7 +/- 0.6 in Group Sm, P < 0.05). TGF-beta(1) (pg/g) (1452.4 +/- 465.7 vs. 818.9 +/- 202.8 in Group Sm, P < 0.05) and hydroxyproline (mg/g) (5.6 +/- 0.6, vs. 2.4 +/- 0.1 in Group Sm, P < 0.05) were also consistently increased. The upregulation of beta-catenin measured either by counting the cell with positive staining in microscopic field (17.4 +/- 7.9 vs. 9.9 +/- 2.9 in Group Sm, P < 0.05) or by estimation of the proportion of blue-stained area by Masson's trichrome (11.8 +/- 5.6 vs. 4.7 +/- 2.4 in Group Sm) in Group SM + PTX was much more noticeable as than those in Group Sm. The expression of beta-catenin measured by positive cell counts was correlated to TGF-beta(1) concentration in lung tissue (r = 0.758, P < 0.001). PTX per se caused neither fibrosis nor emphysema though expression of beta-catenin and downstream gene cyclin D(1) may also be altered by this medication. CONCLUSIONS: PTX mediated transformation of pulmonary emphysema into pulmonary fibrosis under chronic cigarette smoke exposure is associated with upregulation of beta-catenin and elevation of TGF-beta(1), implying that activation of Wnt/beta-catenin signaling may be involved in the pathogenesis of pulmonary fibrosis. PMID- 21034655 TI - Different apoptotic reactions of dorsal root ganglion A- and B-cells after sciatic nerve axotomy: effect of p75 neurotrophin receptor. AB - BACKGROUND: By unbiased stereological methods, we have observed preferential dorsal root ganglion (DRG) B-cell loss in rodents after nerve injury, and caspase 3 activation and cell loss were related to the present of p75 receptor (p75(NTR)). We hypothesized that DRG B-cells express higher levels of pro apoptotic proteins as compared to A-cells and the expressions of pro-apoptotic proteins can be reduced by depletion of p75(NTR). This study aimed to identify the p75(NTR) involved apoptotic pathway in DRG neurons after nerve injury. METHODS: The p75(NTR) knockout mice (p75-/-) and wildtype Balb/C mice (p75+/+) were used in this study. The expressions of pro-apoptotic proteins, c-Jun-N terminal kinase (JNK), c-jun and p38 in DRG were evaluated with immunohistochemistry 2 and 7 days following unilateral sciatic nerve transection. In addition, extra-cellular related kinase (ERK), a transducer of survival signals, was also tested with immunohistochemistry and Western blotting methods in these animal models. RESULTS: Phosphorylated JNK (P-JNK) and phosphorylated p38 (P-p38) were mainly located in small B-cells, whereas phosphorylated c-jun (P c-jun) was located in both A- and B-cells. Phosphorylated ERK (P-ERK) was located in both B-cells and satellite cells. Axotomy dramatically increased the expressions of P-JNK and P-c-jun (paired t-test), with no influence on the expressions of P-p38 and P-ERK. Furthermore, the increase of P-JNK in p75+/+ mice 2 days after nerve axotomy was approximately 2.2-folds of that in p75-/- mice (P = 0.001, unpaired t-test). CONCLUSION: p75(NTR)-dependent JNK-caspase-3 pathway is involved in DRG B-cell loss after nerve injury and JNK is not the unique upstream of c-jun activation. PMID- 21034657 TI - Proliferation of renal mesangial cells induced by very low density lipoprotein is mediated by p42/44 mitogen activated protein kinase. AB - BACKGROUND: The plasma concentration of very low density lipoprotein (VLDL) is negatively correlated to renal function in glomerular diseases. Effects of VLDL on renal function have been partially attributed to the proliferation of mesangial cells. This study examined the potential role of the p42/44 mitogen activated protein kinase (MAPK) in mesangial cell proliferation induced by VLDL. METHODS: Mesangial cells were treated with VLDL at different concentrations or for different time. The cell cycle of the mesangial cells was analyzed by XTT assay and flow-cytometry; MAPK activity was also assayed. In some experiments, cells were treated with VLDL together with or without 0.1 umol/L PD 98059. RESULTS: Ten to 500 ug/ml VLDL stimulated the proliferation of mesangial cells cultured in vitro in a concentration-dependent manner. The effect was associated with an increase in p42/44 MAPK activity. Increased proliferation of mesangial cells by VLDL was significantly attenuated by PD98059, a specific p42/44 MAPK inhibitor. CONCLUSION: These results indicate that the p42/44 MAPK pathway is an important regulator of mesangial cell proliferation and of renal functions. PMID- 21034656 TI - In vitro susceptibility testing of Aspergillus spp. against voriconazole, itraconazole, posaconazole, amphotericin B and caspofungin. AB - BACKGROUND: During recent years, the incidence of serious infections caused by opportunistic fungi has increased dramatically due to alterations of the immune status of patients with hematological diseases, malignant tumors, transplantations and so forth. Unfortunately, the wide use of triazole antifungal agents to treat these infections has lead to the emergence of Aspergillus spp. resistant to triazoles. The present study was to assess the in vitro activities of five antifungal agents (voriconazole, itraconazole, posaconazole, amphotericin B and caspofungin) against different kinds of Aspergillus spp. that are commonly encountered in the clinical setting. METHODS: The agar-based Etest MIC method was employed. One hundred and seven strains of Aspergillus spp. (5 species) were collected and prepared according to Etest Technique Manuel. Etest MICs were determined with RPMI agar containing 2% glucose and were read after incubation for 48 hours at 35 degrees C. MIC(50), MIC(90) and MIC range were acquired by Whonet 5.4 software. RESULTS: The MIC(90) of caspofungin against A. fumigatus, A. flavus and A. nidulans was 0.094 ug/ml whereas the MIC(90) against A. niger was 0.19 ug/ml. For these four species, the MIC(90) of caspofungin was the lowest among the five antifungal agents. For A. terrus, the MIC(90) of posaconazole was the lowest. For A. fumigatus and A. flavus, the MIC(90) in order of increasing was caspofungin, posaconazole, voriconazole, itraconazole, and amphotericin B. The MIC of amphotericin B against A. terrus was higher than 32 ug/ml in all 7 strains tested. CONCLUSIONS: The in vitro antifungal susceptibility test shows the new drug caspofungin, which is a kind of echinocandins, has good activity against the five species of Aspergillus spp. and all the triazoles tested have better in vitro activity than traditional amphotericin B. PMID- 21034658 TI - Anthocyanins extracted from Chinese blueberry (Vaccinium uliginosum L.) and its anticancer effects on DLD-1 and COLO205 cells. AB - BACKGROUND: Vaccinium uliginosum L. is a type of blueberry found in the Chinese Changbai Mountains. We extracted Vaccinium uliginosum Anthocyanins (A(V.uli)) to investigate its bioactivity on suppressing cancer cells. METHODS: A(V.uli) was extracted under different conditions of temperature (10 degrees C - 35 degrees C), pH 1.0 - 3.0, and diatomaceous earth (1.0 g - 3.0 g), followed by a HPLC analysis for the determination of the ingredients. Its anticancer bioactivities on human colon and colorectal cancer cells (DLD-1 and COLO205) were compared with those on Lonicera caerulea Anthocyanins (A(L.cae)) and Vaccinium myrtillus Anthocyanins (A(V.myr)), using cell viability assays, DNA electrophoresis and nuclear morphology assays. RESULTS: The optimum process of A(V.uli) extraction involved conditions of temperature 20 degrees C, pH 2.0, and diatomaceous earth 1.0 g/50 g of fruit weight. A(V.uli) contained 5 main components: delphinidin (40.70 +/- 1.72)%, cyanidin (3.40 +/- 0.68)%, petunidin (17.70 +/- 0.54)%, peonidin (2.90 +/- 0.63)% and malvidin (35.50 +/- 1.11)%. The malvidin percentage was significantly higher (P < 0.05) than it in A(V.myr). A(V.uli) complied with a dose-dependent repression of cancer cell proliferation with an IC(50) (50% inhibitory concentration) value of 50 ug/ml, and showed greater anticancer efficiency than A(L.cae) and A(V.myr) under the same cell treatment conditions. These observations were further supported by the results of nuclear assays. CONCLUSIONS: The extraction protocol and conditions we used were effective for anthocyanin extraction. A(V.uli) could be a feasible practical research tool and a promising therapeutic source to suppress human colon or colorectal cancers. PMID- 21034659 TI - Cholinergic anti-inflammatory pathway: a possible approach to protect against myocardial ischemia reperfusion injury. AB - OBJECTIVE: A general review was made of studies involving: (1) the concept and mechanism of the cholinergic anti-inflammatory pathway (CAP), (2) the important role of inflammatory response in myocardial ischemia reperfusion (I/R) injury and (3) the evidence and mechanisms by which CAP may provide protection against myocardial I/R injury. DATA SOURCES: The data used in this review were mainly from manuscripts listed in PubMed that were published in English from 1987 to 2009. The search terms were "vagal nerve stimulation", "myocardial ischemia reperfusion injury", "nicotine acetylcholine receptor" and "inflammation". STUDY SELECTION: (1) Clinical and experimental evidence that the inflammatory response induced by reperfusion enhances myocardial I/R injury. (2) Clinical and laboratory evidence that the CAP inhibits the inflammation and provides protection against myocardial I/R injury. RESULTS: The myocardial I/R injury is really an inflammatory process characterized by recruitment of neutrophils into the ischemic myocardium and excessive production of pro-inflammatory cytokines. Because the CAP can modulate the inflammatory response by decreasing the production and release of pro-inflammatory cytokines, it can provide protection against myocardial I/R injury. CONCLUSIONS: The CAP can inhibit the inflammatory response induced by reperfusion and protect against myocardial I/R injury. It represents an exciting opportunity to develop new and novel therapeutics to attenuate the myocardial I/R injury. PMID- 21034660 TI - A rare genetic disease - spondyloepiphyseal dysplasia. PMID- 21034661 TI - Modified one-cut circumcision technique by clamp: reports of 2000 cases. PMID- 21034662 TI - Arteriovenous fistula and pseudoaneurysm as complications of renal biopsy treated with percutaneous intervention. PMID- 21034663 TI - Sequential saphenous vein grafting combined with selective arterialization of middle cardiac vein during off-pump coronary artery bypass surgery. PMID- 21034664 TI - Polytetrafluoroethylene-covered stent implantation with double guiding catheter technique for the treatment of type III coronary perforation after stenting. PMID- 21034665 TI - Limb salvage surgery in a patient with macrodystrophia lipomatosa involving an entire upper extremity. PMID- 21034666 TI - Images for diagnosis . Basal cell carcinoma of the scrotum: report of a case and review of the literature. PMID- 21034667 TI - Images for diagnosis . Papillary thyroid microcarcinoma presenting as skull base metastasis. PMID- 21034668 TI - Computerised decision support systems in order communication for diagnostic, screening or monitoring test ordering: systematic reviews of the effects and cost effectiveness of systems. AB - BACKGROUND: Order communication systems (OCS) are computer applications used to enter diagnostic and therapeutic patient care orders and to view test results. Many potential benefits of OCS have been identified including improvements in clinician ordering patterns, optimisation of clinical time, and aiding communication processes between clinicians and different departments. Many OCS now include computerised decision support systems (CDSS), which are information systems designed to improve clinical decision-making. CDSS match individual patient characteristics to a computerised knowledge base, and software algorithms generate patient-specific recommendations. OBJECTIVES: To investigate which CDSS in OCS are in use within the UK and the impact of CDSS in OCS for diagnostic, screening or monitoring test ordering compared to OCS without CDSS. To determine what features of CDSS are associated with clinician or patient acceptance of CDSS in OCS and what is known about the cost-effectiveness of CDSS in diagnostic, screening or monitoring test OCS compared to OCS without CDSS. DATA SOURCES: A generic search to identify potentially relevant studies for inclusion was conducted using MEDLINE, EMBASE, Cochrane Controlled Trials Register (CCTR), CINAHL (Cumulative Index to Nursing and Allied Health Literature), DARE (Database of Abstracts of Reviews of Effects), Health Technology Assessment (HTA) database, IEEE (Institute of Electrical and Electronic Engineers) Xplore digital library, NHS Economic Evaluation Database (NHS EED) and EconLit, searched between 1974 and 2009 with a total of 22,109 titles and abstracts screened for inclusion. REVIEW METHODS: CDSS for diagnostic, screening and monitoring test ordering OCS in use in the UK were identified through contact with the 24 manufacturers/suppliers currently contracted by the National Project for Information Technology (NpfIT) to provide either national or specialist decision support. A generic search to identify potentially relevant studies for inclusion in the review was conducted on a range of medical, social science and economic databases. The review was undertaken using standard systematic review methods, with studies being screened for inclusion, data extracted and quality assessed by two reviewers. Results were broadly grouped according to the type of CDSS intervention and study design where possible. These were then combined using a narrative synthesis with relevant quantitative results tabulated. RESULTS: Results of the studies included in review were highly mixed and equivocal, often both within and between studies, but broadly showed a beneficial impact of the use of CDSS in conjunction with OCS over and above OCS alone. Overall, if the findings of both primary and secondary outcomes are taken into account, then CDSS significantly improved practitioner performance in 15 out of 24 studies (62.5%). Only two studies covered the cost effectiveness of CDSS: a Dutch study reported a mean cost decrease of 3% for blood tests orders (639 euros) in each of the intervention clinics compared with a 2% (208 euros) increase in control clinics in test costs; and a Spanish study reported a significant increase in the cost of laboratory tests from 41.8 euros per patient per annum to 47.2 euros after implementation of the system. LIMITATIONS: The response rate from the survey of manufacturers and suppliers was extremely low at only 17% and much of the feedback was classified as being commercial-in-confidence (CIC). No studies were identified which assessed the features of CDSS that are associated with clinician or patient acceptance of CDSS in OCS in the test ordering process and only limited data was available on the cost-effectiveness of CDSS plus OCS compared with OCS alone and the findings highly specific. Although CDSS appears to have a potentially small positive impact on diagnostic, screening or monitoring test ordering, the majority of studies come from a limited number of institutions in the USA. CONCLUSIONS: If the findings of both primary and secondary outcomes are taken into account then CDSS showed a statistically significant benefit on either process or practitioner performance outcomes in nearly two-thirds of the studies. Furthermore, in four studies that assessed adverse effects of either test cancellation or delay, no significant detrimental effects in terms of additional utilisation of health-care resources or adverse events were observed. We believe the key current need is for a well designed and comprehensive survey, and on the basis of the results of this potentially for evaluation studies in the form of cluster randomised controlled trials or randomised controlled trials which incorporate process, and patient outcomes, as well as full economic evaluations alongside the trials to assess the impact of CDSS in conjunction with OCS versus OCS alone for diagnostic, screening or monitoring test ordering in the NHS. The economic evaluation should incorporate the full costs of potentially developing, testing, and installing the system, including staff training costs. STUDY REGISTRATION: Study registration 61. PMID- 21034669 TI - New classification of acute myeloid leukemia and precursor-related neoplasms: changes and unsolved issues. AB - The World Health Organization (WHO) classification of lympho-hematopoietic neoplasms is increasingly based on genetic criteria. Here, we focus on changes that, as compared to the 2001 edition, were introduced into the 2008 WHO classification of acute myeloid leukemia (AML) and related precursor neoplasms. The category of AML with recurrent genetic abnormalities was expanded to account for 60% of AML by adding three distinct entities, i.e., AML with t(6,9), inv(3), or t(1;22), and two provisional entities, i.e., AML with mutated NPM1 or CEBPA. These changes have greatly modified the approaches to diagnosis and prognostic stratification of AML patients. To emphasize the need of various parameters for diagnosis, including myelodysplasia (MD)-related cytogenetic abnormalities, history of myelodysplasia or myelodysplasia/myeloproliferative neoplasm, and multilineage dysplasia, the category of "AML with multilineage dysplasia" was re named AML with MD-related changes. Finally, we describe the unique characteristics of myeloid proliferations associated with Down syndrome and blastic plasmacytoid dendritic cell neoplasm. PMID- 21034671 TI - Neurokinin-1 receptor: a new promising target in the treatment of cancer. AB - Substance P (SP) has a widespread distribution in the whole body. After binding to the neurokinin-1 (NK-1) receptor, SP regulates biological functions related to cancer: tumor cell proliferation (favoring tumor growth), angiogenesis, and migration of the tumor cells for invasion and metastasis. SP also exerts an antiapoptotic effect. The peptide is secreted from primary tumors and from peripheral nerves, and reaches the whole body through the blood stream. NK-1 receptors are overexpressed in tumors (cancer cells express more NK-1 receptors than normal cells). By contrast, after binding to NK-1 receptors, the NK-1 receptor antagonists specifically inhibit tumor cell proliferation (tumor cells die by apoptosis), angiogenesis and the migration of the tumor cells. Thus, 1) the SP/NK-1 receptor system plays an important role in the development of cancer, angiogenesis, and metastasis; 2) a common mechanism for cancer cell proliferation mediated by the SP/NK-1 receptor system occurs; 3) NK-1 receptor antagonists act as a broad-spectrum antitumoral agent; 4) the NK-1 receptor could be a new promising target in the treatment of cancer; 5) NK-1 receptor antagonists could improve cancer treatment--the development of antagonist molecules of the NK-1 receptor represents an important opportunity for exploiting these molecules as novel therapeutic agents. PMID- 21034672 TI - TRPing up the genome: Tandem repeat polymorphisms as dynamic sources of genetic variability in health and disease. AB - Repetitive DNA sequences constitute a large fraction of the genomes of humans and other animal species. Tandem repeats are a major class of repetitive DNA and the extent of their polymorphic distributions and functions within the human genome are only beginning to be explored. Tandem repeat polymorphisms (TRPs) provide a unique source of genomic variability and recent evidence suggests they can modulate a range of biological processes, in developing and mature organisms. Tandem repeats can change length during meiosis and mitosis, providing a dynamic source of genetic variation which may not only influence evolutionary processes, but also somatic cellular selection. Furthermore, recent evidence for post mitotic instability of specific tandem repeats in neurons supports their additional possible roles in neuronal function and dysfunction. The mutation rate of TRPs is higher and the extent of polymorphism is far more diverse than that of single nucleotide polymorphisms (SNPs). Whereas SNPs are invariably binary in nature, TRPs generally exhibit extended digital (multiallelic) distributions, which provide a much richer range of polymorphic variants, and thus a wider possible range of genetic contribution to disease susceptibility. Expansions in tandem repeats are known to cause many monogenic disorders, which mainly affect the nervous system, including Huntington's disease, various spinocerebellar ataxias, other polyglutamine diseases, Friedreich ataxia, fragile X syndrome, myoclonic epilepsy, polyalanine disorders, and myotonic dystrophy. Furthermore, it has recently been proposed that TRPs could help solve the conundrum of "missing heritability" produced by SNP-based genome-wide association studies of various polygenic complex diseases. There are hundreds of thousands of unique tandem repeats in the human genome and their polymorphic distributions have the potential to greatly influence functional diversity and disease susceptibility. Recent discoveries in this expanding field are discussed, with a focus on the role of TRPs in brain development, function, and dysfunction. PMID- 21034670 TI - Gene therapy and virotherapy: novel therapeutic approaches for brain tumors. AB - Glioblastoma multiforme (GBM) is a deadly primary brain tumor in adults, with a median survival of ~12-18 months post-diagnosis. Despite recent advances in conventional therapeutic approaches, only modest improvements in median survival have been achieved; GBM usually recurs within 12 months post-resection, with poor prognosis. Thus, novel therapeutic strategies to target and kill GBM cells are desperately needed. Our group and others are pursuing virotherapy and gene therapy strategies for the treatment of GBM. In this review, we will discuss various virotherapy and gene therapy approaches for GBM currently under pre clinical and clinical evaluation including direct or conditional cytotoxic, and/or immunostimulatory approaches. We also discuss cutting-edge technologies for drug/gene delivery and targeting brain tumors, including the use of stem cells as delivery platforms, the use of targeted immunotoxins, and the therapeutic potential of using GBM microvesicles to deliver therapeutic siRNAs or virotherapies. Finally, various animal models available to test novel GBM therapies are discussed. PMID- 21034673 TI - FOXP3 as an X-linked tumor suppressor. AB - The FOXP3 gene was initially identified because its mutation caused lethal autoimmune diseases in mice and humans. Mice with heterozygous mutations of FoxP3 (mouse version of the FOXP3 gene) succumb to mammary tumors spontaneously, while those with prostate-specific deletions develop prostate intraepithelial neoplasia. Somatic mutations, deletion, and epigenetic inactivation of FOXP3 are widespread among human breast and prostate cancers. Unlike autosomal tumor suppressor genes that are usually inactivated by mutations in both alleles, X linked FOXP3 mutations in cancer samples are usually heterozygous, with the wildtype allele selectively inactivated in cancer. This skewed X-inactivation suggests a new approach to reactivation of FOXP3 for cancer therapy. PMID- 21034674 TI - The next generation of antibody-drug conjugates comes of age. AB - Monoclonal antibodies (mAbs) and derivatives are currently the fastest growing class of therapeutic molecules. More than 30 G-type immunoglobulins (IgG) and related agents have been approved over the past 25 years mainly for cancers and inflammatory diseases. In oncology, mAbs are often combined with cytotoxic drugs to enhance their therapeutic efficacy. Alternatively, small anti-neoplastic molecules can be chemically conjugated to mAbs, used both as carriers (increased half-life) and as targeting agents (selectivity). Potential benefits of antibody drug conjugates (ADCs), strategies, and development challenges are discussed in this review. Several examples of ADCs are presented with emphasis on three major molecules currently in late clinical development as well as next generation thio mAbs conjugates with improved therapeutic index. PMID- 21034675 TI - The role of telomeres and telomerase in endocrine tumors. AB - The enzyme, telomerase, is a reverse transcriptase that synthesizes the telomeric ends of linear chromosomes and compensate for the shortened telomere, thereby immortalizing the cell. It is present at the blastocyst stage of embryological development, low or undetectable in most somatic cells, and activated in cancer. Because of its strong association with cancer cell immortalization and proliferation, numerous attempts have been made to capitalize on its diagnostic, prognostic, and therapeutic potential. Herein we discuss the role of telomerase in normal, benign, and cancerous endocrine tissues. PMID- 21034676 TI - Sublingual specific immunotherapy. AB - Sublingual application of allergen extracts in specific immunotherapy is a modern approach aimed at improving patient treatment acceptance through reduced serious side effects. This therapeutic approach has proven to be efficacious and safe for the treatment of allergies caused by airborne allergens: 1) studies have shown a rapid onset of action, as early as seven days after beginning treatment; 2) a strong effect during treatment, superior to most forms of symptomatic treatment; 3) a lasting effect after cessation; 4) a preventive effect against new sensitizations and new-onset asthma; and 5) an unprecedented safety profile compared to the subcutaneous route. SLIT is an established treatment option for moderate to severe allergic rhinoconjunctivitis with or without asthma, which can be given to adults as well as to children above five. The complexity of the treatment of this condition mandates expert care by an experienced allergologist. PMID- 21034677 TI - Development of anti-cancer drugs. AB - Every new anti-cancer drug or drug combination is evaluated for safety and efficacy before being approved. Clinical development of cytotoxic anticancer drugs classically follows three main phases. Phase I trials represent the first administration of a new drug or combination to human beings. Their primary goal is to determine the recommended phase two dose and also to collect toxicity, pharmacokinetic and pharmacodynamic data. Phase II trials are screening studies aimed at identifying signals of anti-tumor activity in a specific tumor type and setting. Phase III trials aim to compare the efficacy of a new treatment with standard of care and can lead to regulatory approval when positive. The recent emergence of molecularly targeted agents has challenged the traditional developmental pathway for anti-cancer drugs. Using biomarker enriched patient populations has been successful for a few agents. Otherwise, new types of trials have been proposed for these agents in an attempt to elucidate their mechanism of action, such as phase 0 trials and "window of opportunity" trials. These two types of trials and the classical three phase trials are discussed in detail. PMID- 21034678 TI - Some unmet challenges in the immunology of viral infections. AB - Viral immunology is a rapidly evolving field. Major strides have been made in our understanding of innate and adaptive immune responses to viruses, largely based on highly reductionistic animal infection models, but more recently in humans, with validation that fundamental immunological concepts do in fact translate into clinical science well. From these studies there has emerged an appreciation of the enormous complexity of the immune response to viral infections as well as the diverse array of strategies developed by viruses to deal with immune detection. In this review, we highlight some of the major challenges we face in unraveling this complexity and summarize current efforts under way to improve the efficacy of viral vaccines. PMID- 21034679 TI - Cost-effectiveness of psychotherapy for cluster C personality disorders: a decision-analytic model in the Netherlands. AB - OBJECTIVE: To conduct a formal economic evaluation of various dosages of psychotherapy for patients with avoidant, dependent, and obsessive-compulsive (ie, cluster C) personality disorders (Structured Interview for DSM-IV Personality criteria). METHOD: We developed a decision-analytic model to assess the cost-effectiveness of 5 dosages of psychotherapy (ie, long-term outpatient psychotherapy, short-term and long-term day hospital psychotherapy, and short term and long-term inpatient psychotherapy) over a 5-year time horizon in terms of cost per recovered patient-year and cost per quality-adjusted life-year (QALY). Model parameters were estimated using data from 466 patients with cluster C personality disorders who were admitted to 6 specialist centers of psychotherapy in The Netherlands and assigned to 1 of the 5 treatment groups. Probabilistic analysis was conducted to explore the stability of results over uncertain data ranges. Analyses were conducted from both societal and payer perspectives. RESULTS: From the societal perspective and below a threshold of ? 2,637 (US $3,351.92) per recovered patient-year, short-term day hospital psychotherapy resulted in the highest level of benefit for its cost; above the threshold, short-term inpatient psychotherapy was the most cost-effective choice. In terms of cost per QALY, this switch point was at a threshold value of ? 16,570 (US $21,062.29) per QALY. From the payer perspective, the optimal strategy changed from short-term day hospital psychotherapy to short-term inpatient psychotherapy at threshold values of ? 9,874 (US $12,550.94) per recovered patient-year and ? 66,302 (US $84,277.13) per QALY. CONCLUSIONS: This study indicates that short-term day hospital psychotherapy and short-term inpatient psychotherapy are the most cost-effective treatment strategies for patients with cluster C personality disorders. The ultimate selection depends on what cost effectiveness threshold is considered acceptable and what perspective is adopted. PMID- 21034680 TI - Prophylactic treatment with escitalopram of pegylated interferon alfa-2a-induced depression in hepatitis C: a 12-week, randomized, double-blind, placebo controlled trial. AB - BACKGROUND: Depression is one of the main reasons for treatment withdrawal and failure in chronic hepatitis C patients treated with interferon. Antidepressants are useful for its treatment, but whether they can also be used for prevention has yet to be established. METHOD: To evaluate the efficacy and safety of escitalopram for preventing interferon alfa-2a-induced depression, we conducted an investigator-initiated multicenter, randomized, double-blind, placebo controlled trial in 133 chronic hepatitis C patients without baseline mental disorders who were randomly assigned to receive escitalopram or placebo during the first 12 weeks of treatment. Primary efficacy outcomes were the development of DSM-IV major depression and scores on the Montgomery-Asberg Depression Rating Scale (MADRS) and the Hospital Anxiety and Depression Scale (HADS). Primary safety end points were biochemical and virological responses. Patients were recruited between March 2005 and July 2006. RESULTS: Rates of major depression were low (5.4%) and did not differ between placebo (3.2%) and escitalopram (7.6%). MADRS and HADS scores significantly increased during treatment (P < .001 and P = .028, respectively), but there were no differences between treatment groups. Sustained virological response was achieved by 69.2% of patients, 70.4% in the placebo group and 67.9% in the escitalopram group. CONCLUSIONS: Findings do not support the use of an antidepressant to prevent interferon-induced depression during the first 12 weeks of treatment in chronic hepatitis C patients at low psychiatric risk. Future studies should be directed to subpopulations of patients at high psychiatric risk. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00166296. PMID- 21034681 TI - Cognitive development in adults with attention-deficit/hyperactivity disorder: a controlled study in medication-naive adults across the adult life cycle. AB - OBJECTIVE: This study evaluated the association between attention deficit/hyperactivity disorder (ADHD) and psychometrically defined cognitive variables across the adult life span, using data from a large controlled study of adults with and without ADHD. METHOD: Comparisons were made between 2 groups of adults: participants with DSM-IV-diagnosed ADHD who had never received pharmacotherapy for their ADHD (n = 116) and 146 control participants. Subjects received a battery assessing IQ, neuropsychological measures, and academic testing. We modeled cognitive measures as a function of age and group status using linear regression. The study was conducted at Massachusetts General Hospital, Boston, between 1998 and 2003. RESULTS: ADHD and control subjects maintained similar, statistically significant differences in all psychometrically assessed measures of cognition within each decade that was represented (all P values < .01). CONCLUSION: The negative impact of ADHD on multiple, nonoverlapping, psychometrically assessed measures of cognition remained constant across the life cycle, suggesting that the association between ADHD and cognition neither improves nor deteriorates across the life cycle. PMID- 21034682 TI - Filicide in offspring of parents with severe psychiatric disorders: a population based cohort study of child homicide. AB - OBJECTIVE: Although rare in absolute terms, risk of homicide is markedly elevated among children of parents with mental disorders. Our aims were to examine risk of child homicide if 1 or both parents had a psychiatric history, to compare effects by parental sex and diagnostic group, and to assess likelihood of child homicide being perpetrated by parents according to their psychiatric history. METHOD: A prospective, register-based cohort study using the entire Danish population born between January 1, 1973, and January 1, 2007, was conducted. Follow-up of the cohort members began on their date of birth and ended on January 1, 2007; their 18th birthday; their date of death; or their date of emigration, whichever came first. We used the Danish national registers from 1973 to 2007 to study homicide risk between children whose parents were previously admitted to a psychiatric hospital, including diagnosis-specific analyses, versus their unexposed counterparts. In addition, we used police records during 2000 to 2005 to examine whether or not 1 of the parents was the perpetrator. Rates of homicide were analyzed using survival analysis. RESULTS: Children of parents previously admitted to a psychiatric hospital had an overall higher risk of being homicide victims (MRR = 8.94; 95% CI, 6.56-12.18). The risk differed according to parental sex and psychiatric diagnosis (ICD-8 and ICD-10 criteria). The absolute risk of homicide was 0.009% if neither parent had been admitted before the birth of their child and 0.051% if 1 of the parents had previously been admitted. During 2000 to 2005, 88% of the child homicide cases were filicide victims. This percentage was not significantly different for parents with a previous psychiatric admission versus those without such a history. CONCLUSIONS: In the large majority of Danish child-homicide cases, a parent was the perpetrator, regardless of whether there had been parental admission to a psychiatric hospital. Children of parents previously admitted had a higher risk of being homicide victims, and risks were especially high in young children whose mothers were hospitalized with affective disorders or schizophrenia. However, the relative risks presented in the current study are based on extremely rare events, and the overwhelming majority of children whose parents have a psychiatric history do not become homicide victims. PMID- 21034683 TI - Becoming the center of attention in social anxiety disorder: startle reactivity to a virtual audience during speech anticipation. AB - OBJECTIVE: A detailed understanding of how individuals diagnosed with social anxiety disorder (SAD) respond physiologically under social-evaluative threat is lacking. Our aim was to isolate the specific components of public speaking that trigger fear in vulnerable individuals and best discriminate between SAD and healthy individuals. METHOD: Sixteen individuals diagnosed with SAD (DSM-IV-TR criteria) and 16 healthy individuals were enrolled in the study from December 2005 to March 2008. Subjects were asked to prepare and deliver a short speech in a virtual reality (VR) environment. The VR environment simulated standing center stage before a live audience and allowed us to gradually introduce social cues during speech anticipation. Startle eye-blink responses were elicited periodically by white noise bursts presented during anticipation, speech delivery, and recovery in VR, as well as outside VR during an initial habituation phase, and startle reactivity was measured by electromyography. Subjects rated their distress at 4 timepoints in VR using a 0-10 scale, with anchors being "not distressed" to "highly distressed." State anxiety was measured before and after VR with the Spielberger State-Trait Anxiety Inventory. RESULTS: Individuals with SAD reported greater distress and state anxiety than healthy individuals across the entire procedure (P values < .005). Analyses of startle reactivity revealed a robust group difference during speech anticipation in VR, specifically as audience members directed their eye gaze and turned their attention toward participants (P < .05, Bonferroni-corrected). CONCLUSIONS: The VR environment is sufficiently realistic to provoke fear and anxiety in individuals highly vulnerable to socially threatening situations. Individuals with SAD showed potentiated startle, indicative of a strong phasic fear response, specifically when they perceived themselves as occupying the focus of others' attention as speech time approached. Potentiated startle under social-evaluative threat indexes SAD-related fear of negative evaluation. PMID- 21034684 TI - Longitudinal Assessment of Manic Symptoms (LAMS) study: background, design, and initial screening results. AB - OBJECTIVE: To describe the design of a longitudinal study of youth with elevated symptoms of mania (ESM), as well as the prevalence and correlates of manic symptoms. Bipolar disorder in youth is serious and is surrounded by controversy about its phenomenology, course, and treatment. Yet, there are no longitudinal studies of youth selected only for ESM, the phenomenological hallmark. The study's objective is to document the rate and sociodemographic correlates of ESM in children attending outpatient psychiatric clinics. METHOD: Parents of 3,329 children aged 6-12 years visiting 10 outpatient clinics were asked to complete the Parent General Behavior Inventory 10-Item Mania Scale (PGBI-10M). Children with PGBI-10M scores >= 12 (ESM positive-screen [ESM+]) and a matched sample of ESM screen-negative (ESM-) children were invited to enroll in the longitudinal study. The sample was accrued from November 14, 2005, to November 28, 2008. RESULTS: Most of the children whose parents filled out the PGBI-10M (N = 2,622, 78.8%) participated in the study. Nonparticipants were slightly younger (mean age = 9.1 years [SD = 2.0 years] versus 9.4 years [SD = 2.0 years] for participants; t3327 = 4.42, P < .001). Nearly half of the participants (43%) were ESM+; these were more likely to be Latino (4.2% versus 2.5% for ESM-; chi(2)1 = 5.45, P = .02), younger (mean age = 9.3 years [SD = 2.0 years] versus 9.6 years [SD = 1.9 years] for ESM-; t2620 = 3.8, P < .001), and insured by Medicaid (48.4% versus 35.4% for ESM-; chi(2)1 = 45.00, P < .001). There were no sociodemographic differences between those who did versus did not agree to enroll in the longitudinal portion (yes to enrollment: n = 621, 55.2%; no to enrollment: n = 503, 44.8%). Four items best discriminated ESM+ children from ESM- children. Three of the 4 items were not the most commonly endorsed items, but all were indicative of behavioral extremes. CONCLUSIONS: Data suggest that ESM+ is not rare in 6- to 12-year-olds. Children who are ESM+ show behavioral extremes, including rapid mood shifts, compared to ESM- children. PMID- 21034685 TI - Characteristics of children with elevated symptoms of mania: the Longitudinal Assessment of Manic Symptoms (LAMS) study. AB - OBJECTIVE: The aim of the Longitudinal Assessment of Manic Symptoms (LAMS) study is to examine differences in psychiatric symptomatology, diagnoses, demographics, functioning, and psychotropic medication exposure in children with elevated symptoms of mania (ESM) compared to youth without ESM. This article describes the initial demographic information, diagnostic and symptom prevalence, and medication exposure for the LAMS cohort that will be followed longitudinally. METHOD: Guardians of consecutively ascertained new outpatients 6 to 12 years of age presenting for treatment at one of 10 university-affiliated mental health centers were asked to complete the Parent General Behavior Inventory-10-Item Mania Scale (PGBI-10M). Patients with scores >= 12 on the PGBI-10M (ESM+) and a matched sample of patients who screened negative (ESM-) were invited to participate. Patients were enrolled from December 13, 2005, to December 18, 2008. RESULTS: 707 children (621 ESM+, 86 ESM-; mean [SD] age = 9.4 [2.0] years) were evaluated. The ESM+ group, compared to the ESM- group, more frequently met DSM-IV criteria for a mood disorder (P < .001), bipolar spectrum disorders (BPSD; P < .001), and disruptive behavior disorders (P < .01). Furthermore, they showed poorer overall functioning and more severe manic, depressive, attention deficit/hyperactivity, disruptive behavioral, and anxiety symptoms. Nevertheless, rates of BPSD were relatively low in the ESM+ group (25%), with almost half of these BPSD patients (12.1% of ESM+ patients) meeting DSM-IV criteria for bipolar disorder not otherwise specified. ESM+ children with BPSD had significantly more of the following: current prescriptions for antipsychotics, mood stabilizers, and anticonvulsants (P < .001 for each); psychiatric hospitalizations (P < .001); and biological parents with elevated mood (P = .001 for mothers, P < .013 for fathers). ESM+ children with BPSD were also lower functioning compared to ESM+ children without BPSD. CONCLUSIONS: Although ESM+ was associated with higher rates of BPSD than ESM-, 75% of ESM+ children did not meet criteria for BPSD. Results suggest that longitudinal assessment is needed to examine which factors are associated with diagnostic evolution to BPSD in children with elevated symptoms of mania. PMID- 21034686 TI - Antidepressants for the acute treatment of bipolar depression: a systematic review and meta-analysis. AB - OBJECTIVE: The role of antidepressants in the acute treatment of bipolar depression remains a contentious issue. A previous meta-analysis of randomized controlled trials (RCTs) concluded that antidepressants were effective and safe for bipolar depression. Several trials published since then suggest that antidepressants may not be as beneficial as previously concluded. The current systematic review and meta-analyses reexamine the efficacy and safety of antidepressant use for the acute treatment of bipolar depression. DATA SOURCES: EMBASE, MEDLINE, CINAHL, PsycINFO, and the Cochrane Central Register of Controlled Trials databases were searched for double-blind RCTs published from 2003 to 2009 using the following diagnostic medical subject heading (MESH) terms: bipolar disorder, bipolar depression, bipolar I disorder, bipolar II disorder, bipolar III disorder, bipolar mania, cyclothymia, manic depressive psychosis, mixed mania and depression, and rapid cycling and bipolar disorder. Databases of trial registries were also searched for unpublished RCTs. These searches were supplemented by hand searches of relevant articles and review articles. STUDY SELECTION: Trials that compared acute (< 16 wk) antidepressant treatment with either an active drug or a placebo comparator in adult bipolar patients, depressive phase were eligible for inclusion. Main outcome measures were clinical response, remission, and affective switch. DATA SYNTHESIS: Six RCTs (N = 1,034) were identified since publication in 2004 of the first meta-analysis that assessed antidepressant use in the acute treatment of bipolar depression. These studies were combined with earlier studies for a total of 15 studies containing 2,373 patients. Antidepressants were not statistically superior to placebo or other current standard treatment for bipolar depression. Antidepressants were not associated with an increased risk of switch. Studies that employed more sensitive criteria to define switch did report elevated switch rates for antidepressants. CONCLUSIONS: Although antidepressants were found to be safe for the acute treatment of bipolar depression, their lack of efficacy may limit their clinical utility. Further high-quality studies are required to address the existing limitations in the literature. PMID- 21034687 TI - Randomized controlled trial of interventions for young people at ultra high risk for psychosis: 6-month analysis. AB - OBJECTIVE: Cognitive therapy and/or low-dose antipsychotic administered during the prodromal phase of schizophrenia may prevent or delay the onset of full-blown illness. However, it is unclear which of these treatments are most effective, how long treatment should be given, and whether effects will be sustained over a prolonged period. METHOD: In order to examine these issues, we conducted a randomized controlled trial of cognitive therapy + risperidone; cognitive therapy + placebo; and supportive therapy + placebo in young people at ultra high risk for developing a psychotic disorder (that is, putatively prodromal). The main outcome was transition to psychotic disorder, with level of symptoms and functioning the secondary outcomes. This article reports the interim 6-month follow-up results. The study was conducted from August 2000 to May 2007. RESULTS: Of a possible 464 eligible ultra high risk individuals, 115 were recruited to the randomized controlled trial (cognitive therapy + risperidone, n = 43; cognitive therapy + placebo, n = 44; and supportive therapy + placebo, n = 28). An additional 78 individuals agreed to follow-up assessments but not to randomization ("monitoring group," n = 78). At 6 months, 8 of the 115 participants (7.0%) and 4 of the monitoring group (5.1%) had developed psychotic disorder. There were no significant differences between the 3 randomized groups (log rank test, P = .92) or between all 4 groups (log rank test, P = .93). There was also no difference between the 4 groups in secondary measures, with all groups showing a reduction in symptoms and increased functioning. CONCLUSIONS: Rates of transition to psychosis were lower than expected, particularly in the control supportive therapy + placebo group. This may have accounted for the negative finding, as the sample was therefore underpowered to find any difference between groups. Alternatively, it may be that all treatments were equally effective or equally ineffective at 6 months. TRIAL REGISTRATION: http://www.anzctr.org.au Identifier: ACTRN012605000247673. PMID- 21034688 TI - The effect of exercise in clinically depressed adults: systematic review and meta analysis of randomized controlled trials. AB - OBJECTIVE: To assess the effectiveness of exercise in adults with clinical depression. DATA SOURCES: The databases CINAHL, Embase, Cochrane Database of Systematic reviews, Cochrane Controlled Trials Register, MEDLINE, and PsycINFO were searched (1806-2008) using medical subject headings (MeSH) and text word terms depression, depressive disorder and exercise, aerobic, non-aerobic, physical activity, physical fitness, walk*, jog*, run*, bicycling, swim*, strength, and resistance. STUDY SELECTION: Randomized trials including adults with clinical depression according to any diagnostic system were included. DATA EXTRACTION: Two investigators evaluated trials using a prepiloted structured form. DATA SYNTHESIS: Thirteen trials were identified that fulfilled the inclusion criteria. Eight had adequate allocation concealment, 6 had a blinded outcome, and 5 used intention-to-treat analyses. The pooled standardized mean difference (SMD) calculated using a random-effects model was -0.40 (95% CI, -0.66 to -0.14), with evidence of heterogeneity between trials (I(2) = 57.2%, P = .005). There was an inverse association between duration of intervention and the magnitude of the association of exercise with depression (P = .002). No other characteristics were related to between-study heterogeneity. Pooled analysis of 5 trials with long-term follow-up (ie, that examined outcomes beyond the end of the intervention) suggested no long-term benefit (SMD, -0.01; 95% CI, -0.28 to 0.26), with no strong evidence of heterogeneity in this pooled analysis (I(2) = 23.4%, P = .27). There was no strong statistical evidence for small study bias (P > .27). Only 3 studies were assessed as high quality (adequately concealed random allocation, blinded outcome assessment, and intention-to-treat analysis). When we pooled results from these, the estimated beneficial effect of exercise was more modest (SMD, -0.19; 95% CI, -0.70 to 0.31) than the pooled result for all 13 studies, with no strong evidence of benefit. CONCLUSIONS: Our results suggest a short-term effect of exercise on depression: on average, depression scores 0.4 of a standard deviation lower in clinically depressed patients randomly assigned to an exercise intervention at the end of that intervention compared to those randomly assigned to a none exercise group. There is little evidence of a long term beneficial effect of exercise in patients with clinical depression. PMID- 21034689 TI - Exploring regional variation in antipsychotic coprescribing practice: a Danish questionnaire survey. AB - OBJECTIVE: The pharmacologic treatment of schizophrenia is characterized by excessive use of antipsychotic polypharmacy, which reflects a gap between evidence and practice. The aim of the present study was to investigate regional differences in treatment setting characteristics and in physician and nurse attitudes toward antipsychotic polypharmacy and clinical guidelines. METHOD: Cross-sectional postal questionnaire survey directed to physicians and nurses at 2 pairs of treatment settings in Denmark, characterized by low and high prevalence of antipsychotic polypharmacy, respectively. The questionnaire investigation was conducted during November 2007 to February 2008. RESULTS: Satisfactory response rates were obtained (physicians: 93%; nurses: 87%). The treatment settings with low use of antipsychotic polypharmacy were characterized by raised knowledge/awareness of local antipsychotic treatment guidelines (P = .02 for physicians; P = .01 for nurses). Among physicians, these settings were also characterized by an elevated confidence in these guidelines (P = .01), frequent local educational activities (P < .0001), and increased recent involvement in research (P = .01). Among nurses, a perception of an overwhelming work load (P = .01) and time pressure (P = .003) was significantly more prevalent in treatment settings with high rates of antipsychotic coprescribing, as was the belief in the benefit of antipsychotic polypharmacy augmentation (P = .001). CONCLUSION: Albeit no causal relationships can be inferred from this cross sectional observational study, we recommend the furtherance of a treatment environment characterized by easily accessible clinical guidelines, frequent academic activities, and an unruffled atmosphere. PMID- 21034690 TI - Risperidone long-acting therapy prescribing patterns and their impact on early discontinuation of treatment in a large Medicaid population. AB - OBJECTIVE: Medicaid claims were examined to determine whether utilization of risperidone long-acting therapy (LAT) was consistent with manufacturer's prescribing information recommendations and what factors were associated with early discontinuation. METHOD: Florida Medicaid claims between July 1, 2003, and June 30, 2007, were used. Recipient demographics and diagnoses, provision of oral antipsychotic supplementation during the first 21 days, number of injections received, medication possession ratio, and augmentation/polypharmacy after the first 21 days were assessed. Logistic regression was used to identify factors associated with early discontinuation of risperidone LAT. RESULTS: There were 3,364 individuals who received 4,546 episodes of risperidone LAT. Most recipients were between 18 and 64 years and had schizophrenia or schizoaffective disorder. Median episode length was 106 days. Median number of injections was 5. Supplementation with oral antipsychotic during the first 21 days was provided in 48% of episodes. Mean dosages were 25 mg or less for 28% of episodes and greater than 75 mg for 7% of episodes. Augmentation/polypharmacy after the first 21 days occurred in 43% of episodes. Early risperidone LAT discontinuation was associated with absence of oral supplementation during the first 21 days (P < .001), low (P = .045) or high (P < .001) initial doses of risperidone LAT, prior inpatient treatment (P < .001), having a substance use disorder (P = .001), and being male (P = .036). CONCLUSIONS: Prescribing practices for risperidone LAT were compared with the recommended protocol. Risperidone LAT was typically used with recommended age and diagnostic groups. However, important discrepancies were identified that could have reduced perceived effectiveness and tolerability of risperidone LAT. Early discontinuation was less likely when the recommendations in the manufacturer's prescribing information regarding dosage and supplementation with oral antipsychotics were followed. PMID- 21034691 TI - Peritraumatic heart rate and posttraumatic stress disorder in patients with severe burns. AB - OBJECTIVE: Previous studies have suggested a link between heart rate (HR) following trauma and the development of posttraumatic stress disorder (PTSD). This study expands on previous work by evaluating HR in burn patients followed longitudinally for symptoms of acute stress disorder (ASD) and PTSD. METHOD: Data were collected from consecutive patients admitted to the Johns Hopkins Burn Center, Baltimore, Maryland, between 1997 and 2002. Patients completed the Stanford Acute Stress Reaction Questionnaire (n = 157) to assess symptoms of ASD. The Davidson Trauma Scale was completed at 1 (n = 145), 6 (n = 106), 12 (n = 94), and 24 (n = 66) months postdischarge to assess symptoms of PTSD. Heart rate in the ambulance, emergency room, and burn unit were obtained by retrospective medical chart review. RESULTS: Pearson correlations revealed a significant relationship between HR in the ambulance (r = 0.32, P = .016) and burn unit (r = 0.30, P = .001) and ASD scores at baseline. Heart rate in the ambulance was related to PTSD avoidance cluster scores at 1, 6, 12, and 24 months. In women, HR in the ambulance was correlated with PTSD scores at 6 (r = 0.65, P = .005) and 12 (r = 0.78, P = .005) months. When covariates (gender, beta-blockers, Brief Symptom Inventory Global Severity Index score) were included in multivariate linear regression analyses, ambulance HR was associated with ASD and PTSD scores at baseline and 1 month, and the interaction of ambulance HR and gender was associated with PTSD scores at 6 and 12 months. Multivariate logistic regression results were similar at baseline and 12 months, which included an HR association yet no interaction at 6 months and a marginal interaction at 1 month. CONCLUSIONS: While peritraumatic HR is most robustly associated with PTSD symptom severity, HR on admission to burn unit also predicts the development of ASD. Gender and avoidance symptoms appear particularly salient in this relationship, and these factors may aid in the identification of subgroups for which HR serves as a biomarker for PTSD. Future work may identify endophenotypic measures of increased risk for PTSD, targeting subgroups for early intervention. PMID- 21034692 TI - Levetiracetam in the management of bipolar depression: a randomized, double blind, placebo-controlled trial. AB - OBJECTIVE: To study the efficacy of adjunctive levetiracetam therapy compared with placebo in the treatment of subjects with depression with bipolar disorder. METHOD: This double-blind, placebo-controlled clinical trial randomly assigned outpatients with bipolar disorder type I and type II who were experiencing a major depressive episode (Structured Clinical Interview for DSM-IV Axis I Disorders-Clinician Version criteria) to treatment with either placebo or adjunctive levetiracetam (up to 2,500 mg/d flexibly dosed) for 6 weeks. The subjects were recruited from October 2005 to June 2008. The primary efficacy measure was mean change from baseline to week 6 in the Hamilton Depression Rating Scale (21-item). Secondary efficacy assessments included the Montgomery-Asberg Depression Rating Scale, the Beck Depression Inventory, the Clinical Global Impressions-Bipolar Version scale, the Hamilton Anxiety Rating Scale, and the Young Mania Rating Scale. RESULTS: Of 42 subjects randomly assigned to placebo or drug, 32 received at least 1 postbaseline assessment and thus were included in the analysis. The mean (SD) levetiracetam daily dose at endpoint evaluation was 1,132 (425) mg/d. There was no significant difference in the mean change from baseline to week 6 in the Hamilton Depression Rating Scale scores for levetiracetam compared with placebo. There were no significant differences in any of the secondary outcome measures. CONCLUSIONS: Levetiracetam adjunctive therapy was not superior to placebo in the short-term treatment of subjects with depression with bipolar disorder in the population studied. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT00566150. PMID- 21034693 TI - Can we really accelerate and enhance the selective serotonin reuptake inhibitor antidepressant effect? A randomized clinical trial and a meta-analysis of pindolol in nonresistant depression. AB - OBJECTIVE: Since depression entails not only dramatic personal disruption but also a huge amount of medical and socioeconomic burden, slowness of antidepressant action and difficulties to attain remission are entangled issues to be solved. Given the controversial previous findings with enhancing strategies such as pindolol, we examined whether the speed of selective serotonin reuptake inhibitor (SSRI) action can be truly accelerated with optimized pindolol dosage. Additionally, we aimed at elucidating whether pindolol benefits emerge, particularly in a population with nonresistant depression. METHOD: Thirty outpatients with major depressive disorder (DSM-IV criteria) recruited between December 2002 and November 2005 were randomly assigned to receive citalopram + pindolol (5 mg tid) or citalopram + placebo for 6 weeks in a double-blind randomized clinical trial. A meta-analysis of randomized controlled trials of pindolol augmentation in patients with nonresistant depression was also performed. Outcome criteria were based on the 17-item Hamilton Depression Rating Scale. For the meta-analysis, efficacy was assessed by the number of treatment responders at 2 weeks and 4-6 weeks. RESULTS: Clinical trial outcomes: Repeated measures analysis of variance showed a significant group-by-time interaction (P = .01). Cumulative percentage showed a trend for sustained response (odds ratio [OR] = 2.09; 95% CI, 0.914-4.780; P = .08) and a well-defined increased likelihood of sustaining remission (OR = 5.00; 95% CI, 1.191-20.989; P = .03) in pindolol receivers. Median survival time until first response was 65% less in the pindolol group (22 days vs 30 days; P = .03). The negative binomial regression model yielded different rates of response per person-day for pindolol and placebo groups (7.6% vs 4.7%, respectively; P = .03). Meta-analysis: Outcome favored pindolol at 2 weeks' time (relative risk [RR] = 1.68; 95% CI, 1.18-2.39; P = .004) and also at 4-6 weeks' time (RR = 1.11; 95% CI, 1.02-1.20; P = .02). CONCLUSIONS: Present findings represent further evidence of the acceleration and enhancement of efficacy with pindolol administered together with SSRIs, displaying a quicker and more pronounced decrease of symptoms in patients with nonresistant major depressive disorder. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00931775. PMID- 21034694 TI - Childhood trauma and depressive symptoms in type 1 diabetes. AB - BACKGROUND: To examine the relationship of childhood trauma to depressive symptoms in type 1 diabetes, a chronic disease in which the frequency of depression is increased. METHOD: One hundred fifty African American patients with type 1 diabetes seen between August 1993 and January 1998 completed the Beck Depression Inventory and Childhood Trauma Questionnaire. They were also genotyped for a functional serotonin transporter promoter polymorphism (5-HTTLPR) that modulates resiliency. Patients who had Beck Depression Inventory scores above and below 14 were compared. RESULTS: Diabetic patients who had Beck Depression Inventory scores >= 14 had experienced significantly more different types of childhood trauma than those with Beck Depression Inventory scores < 14 (P < .001), independent of potential interaction with 5-HTTLPR genotype. CONCLUSIONS: Childhood trauma appears to be a determinant of depressive symptoms in type 1 diabetes, independently of genotype of a functional locus modulating resiliency. PMID- 21034696 TI - Amplification for unilateral hearing loss. PMID- 21034697 TI - Impact of spectrally asynchronous delays on consonant voicing perception. AB - BACKGROUND: A possible voicing cue used to differentiate voiced and voiceless cognate pairs is envelope onset asynchrony (EOA). EOA is the time between the onsets of two frequency bands of energy (in this study one band was high-pass filtered at 3000 Hz, the other low-pass filtered at 350 Hz). This study assessed the perceptual impact of manipulating EOA on voicing perception of initial stop consonants, and whether normal-hearing and hearing-impaired listeners were sensitive to changes in EOA as a cue for voicing. PURPOSE: The purpose of this study was to examine the effect of spectrally asynchronous auditory delay on the perception of voicing associated with initial stop consonants by normal-hearing and hearing-impaired listeners. RESEARCH DESIGN: Prospective experimental study comparing the perceptual differences of manipulating the EOA cues for two groups of listeners. STUDY SAMPLE: Thirty adults between the ages of 21 and 60 yr completed the study: 17 listeners with normal hearing and 13 listeners with mild moderate sensorineural hearing loss. DATA COLLECTION AND ANALYSIS: The participants listened to voiced and voiceless stop consonants within a consonant vowel syllable structure. The EOA of each syllable was varied along a continuum, and identification and discrimination tasks were used to determine if the EOA manipulation resulted in categorical shifts in voicing perception. In the identification task the participants identified the consonants as belonging to one of two categories (voiced or voiceless cognate). They also completed a same different discrimination task with the same set of stimuli. Categorical perception was confirmed with a d-prime sensitivity measure by examining how accurately the results from the identification task predicted the discrimination results. The influence of EOA manipulations on the perception of voicing was determined from shifts in the identification functions and discrimination peaks along the EOA continuum. The two participant groups were compared in order to determine the impact of EOA on voicing perception as a function of syllable and hearing status. RESULTS: Both groups of listeners demonstrated a categorical shift in voicing perception with manipulation of EOA for some of the syllables used in this study. That is, as the temporal onset asynchrony between low- and high-frequency bands of speech was manipulated, the listeners' perception of consonant voicing changed between voiced and voiceless categories. No significant differences were found between listeners with normal hearing and listeners with hearing loss as a result of the EOA manipulation. CONCLUSIONS: The results of this study suggested that both normal-hearing and hearing-impaired listeners likely use spectrally asynchronous delays found in natural speech as a cue for voicing distinctions. While delays in modern hearing aids are less than those used in this study, possible implications are that additional asynchronous delays from digital signal processing or open-fitting amplification schemes might cause listeners with hearing loss to misperceive voicing cues. PMID- 21034695 TI - Number needed to treat to harm for discontinuation due to adverse events in the treatment of bipolar depression, major depressive disorder, and generalized anxiety disorder with atypical antipsychotics. AB - OBJECTIVE: To estimate the number needed to treat to harm (NNTH) for discontinuation due to adverse events with atypical antipsychotics relative to placebo during the treatment of bipolar depression, major depressive disorder (MDD), and generalized anxiety disorder (GAD). DATA SOURCES: English-language literature published and cited in MEDLINE from January 1966 to May 2009 was searched with the terms antipsychotic, atypical antipsychotic, generic and brand names of atypical antipsychotics, safety, tolerability, discontinuation due to adverse events, somnolence, sedation, weight gain, akathisia, or extrapyramidal side effect; and bipolar depression, major depressive disorder, or generalized anxiety disorder; and randomized, placebo-controlled clinical trial. This search was augmented with a manual search. STUDY SELECTION: Studies with a cumulative sample of >= 100 patients were included. DATA EXTRACTION: The NNTHs for discontinuation due to adverse events, somnolence, sedation, >= 7% weight gain, and akathisia relative to placebo were estimated with 95% confidence intervals to reflect the magnitude of variance. DATA SYNTHESIS: Five studies in bipolar depression, 10 studies in MDD, and 4 studies in GAD were identified. Aripiprazole and olanzapine have been studied in bipolar depression and refractory MDD. Only quetiapine extended release (quetiapine-XR) has been studied in 3 psychiatric conditions with different fixed dosing schedules. For aripiprazole, the mean NNTH for discontinuation due to adverse events was 14 in bipolar depression, but was not significantly different from placebo in MDD. For olanzapine, the mean NNTHs were 24 in bipolar depression and 9 in MDD. The risk for discontinuation due to adverse events during quetiapine-XR treatment appeared to be associated with dose. For quetiapine-XR 300 mg/d, the NNTHs for discontinuation due to adverse events were 9 for bipolar depression, 8 for refractory MDD, 9 for MDD, and 5 for GAD. CONCLUSIONS: At the same dose of quetiapine-XR, patients with GAD appeared to have a lower tolerability than those with bipolar depression or MDD. Due to flexible dosing, the risk for discontinuation due to adverse events in the treatment of bipolar depression, MDD, or GAD with other atypical antipsychotics could not be compared. PMID- 21034698 TI - Hearing aid fitting outcome: clinical application and psychometric properties of a Swedish translation of the international outcome inventory for hearing aids (IOI-HA). AB - BACKGROUND: The International Outcome Inventory for Hearing Aids (IOI-HA) is a seven-item hearing-specific questionnaire. It was developed with the purpose of evaluating the efficacy of hearing aid rehabilitation. Few psychometric properties have been presented for a Swedish translation of the IOI-HA. Furthermore, previous studies have examined the IOI-HA in mainly sensorineural hearing losses, and we do not know how the type of hearing loss affects the outcome. PURPOSE: To evaluate the hearing aid fitting outcome measured in a clinical setting using a Swedish translation of the International Outcome Inventory for Hearing Aids (IOI-HA), to determine the psychometric properties of the translation, and to examine how a number of demographic variables such as type of hearing loss affect the outcome. RESEARCH DESIGN: A descriptive and correlational study in a retrospective sample. STUDY SAMPLE: Two hundred and twenty-four (107 females and 117 males; ages 27-94 yr with an average of 66.1 yr) first-time hearing aid users. INTERVENTION: Mostly digital hearing aids (97.8%) were fitted monaurally (60%) or binaurally (40%) between 2007 and 2009. DATA COLLECTION AND ANALYSIS: The subjects were mailed the IOI-HA questionnaire six months after their final appointment, and the completed questionnaire was returned by mail to the clinic. The psychometric properties were evaluated and compared to previous studies using the IOI-HA. The associations between the outcome scores and a number of demographic variables (age, gender, degree of hearing loss, type of hearing loss, number of hearing aids, and type of hearing aids) were examined. Based on the pure tone audiograms, the subjects were divided into three groups; those with conductive hearing losses, sensorineural hearing losses, and mixed hearing losses. For these groups, the differences in outcome measured as IOI-HA were examined. RESULTS: The psychometric properties of the present translation of the IOI-HA showed resemblance in many aspects to previous reports. Furthermore, the type of hearing loss seems to affect the IOI-HA outcome. Hearing loss increases with increasing age, and hearing aid use increases with increasing degree of hearing loss. Subjects with sensorineural hearing losses show significantly poorer scores on items concerning introspective aspects of the outcome in comparison to subjects with mixed hearing losses and subjects with conductive hearing losses. Monaurally fitted subjects tend to report lower scores on average, but monaural or binaural hearing aid fitting do not significantly affect the subjective outcome. CONCLUSIONS: The psychometric properties of the present Swedish translation of the IOI-HA show resemblance in many aspects to previous reports, but the differences observed could be due to differences in the study populations. Overall, the demographic variables examined could not be used as predictors for the hearing aid fitting outcome, and more reliable predictors need to be identified. PMID- 21034699 TI - Sound localization acuity in children with unilateral hearing loss who wear a hearing aid in the impaired ear. AB - BACKGROUND: Disrupted binaural hearing is thought to contribute in part to the academic, social, and communication problems often associated with unilateral hearing loss (UHL) in childhood. It is not known, however, if putting a hearing aid in the impaired ear of a child with UHL will lead to bilateral or binaural benefit. This study seeks to utilize sound localization acuity measurements to assess hearing aid amplification efficacy in children with UHL. PURPOSE: To measure sound localization ability in children with UHL who use a hearing aid in the impaired ear to determine the extent to which amplification, age, early intervention, and degree of hearing loss affects localization acuity. RESEARCH DESIGN: A within-subjects experimental design using repeated measures is used to determine the effect of amplification on localization acuity in children with UHL. A between-subjects experimental design is used to compare localization acuity between children with UHL and age-matched controls with normal hearing. STUDY SAMPLE: Twelve children with UHL who used a hearing aid in the impaired ear and 12 age-matched controls with normal hearing. Children with UHL were divided into two groups based on degree of hearing loss. Children in both groups were divided into two age groups: older children (10-14 yr) and younger children (6-9 yr). DATA COLLECTION AND ANALYSIS: All testing was done in a sound-treated booth with a horizontal array of 15 loudspeakers (radius of 1 m). The stimulus was a spondee word, "baseball": the level averaged 60 dB SPL and randomly roved (+/-8 dB). Each child was asked to identify the location of a sound source. RESULTS: In the experimental study a significant interaction was found between hearing aid amplification and child age. A hearing aid significantly improved localization acuity in younger children with UHL and significantly impaired localization acuity in older children. A significant correlation was found between age at intervention and localization bilateral benefit. Children who were fit earlier showed bilateral benefit whereas children who were fit later showed bilateral interference. Development, however, may play a role in sound localization acuity. When unaided, older children had significantly better localization acuity than younger children with UHL. CONCLUSIONS: A hearing aid can provide bilateral localization benefit to some children with UHL. Early intervention may increase the likelihood of bilateral benefit. However, developmental factors appear to play a role in improving localization abilities over time for children with UHL. Nonetheless, without a means of establishing bilateral benefit with hearing aid amplification, localization performance in children with UHL will rarely equal that of peers. PMID- 21034700 TI - Multiple-ASSR thresholds in infants and young children with hearing loss. AB - BACKGROUND: The multiple auditory steady-state response (multiple ASSR) is a promising technique for determining thresholds for infants and children. However, there are few data for infants and young children with hearing loss where multiple-ASSR thresholds have been compared to frequency-specific gold standard (i.e., behavioral or tone-evoked auditory brainstem response [tone ABR]) measures. PURPOSE: The study compared multiple-ASSR and tone-ABR thresholds and assessed how well "normal" ASSR levels differentiate normal from elevated thresholds. RESEARCH DESIGN: Multiple-ASSR and tone-ABR results (to air conduction stimuli) were obtained in infants and young children with hearing loss or normal hearing. STUDY SAMPLE: 98 infants with hearing loss (53 infants provided thresholds) and 34 infants with normal hearing. DATA COLLECTION AND ANALYSIS: Multiple-ASSR and tone-ABR results were typically completed on the same day. Correlations between ASSR and ABR thresholds, linear regressions, and ASSR minus-ABR threshold difference scores were calculated for each group (normal or hearing loss), and for both groups combined. RESULTS: Multiple-ASSR thresholds (dB HL) were strongly correlated (r = .97) with tone-ABR thresholds (dB nHL) for 500, 1000, 2000, and 4000 Hz. Mean (+/-1 SD) difference scores (ASSR-minus-ABR) were 10.7 +/- 9.0, 9.5 +/- 9.4, 9.2 +/- 9.0, and 6.3 +/- 9.5 dB for 500, 1000, 2000, and 4000 Hz, respectively. The previously published "normal" ASSR levels accurately differentiated normal from elevated thresholds. Out of 523 tests with elevated tone-ABR thresholds, the multiple ASSR was "normal" in only 22 tests. In these 13 infants, other ASSR frequencies were elevated, and thus the infants would not have "passed" the ASSR. CONCLUSIONS: There are few studies of infants and young children comparing ASSR thresholds to frequency-specific gold standard measures, especially using the multiple-ASSR technique. The present study, comparing multiple-ASSR to tone-ABR thresholds, nearly doubles the multiple-ASSR sample size in the literature. The results indicate that the multiple-ASSR and tone-ABR thresholds are strongly correlated, and the "normal" multiple-ASSR levels of 50, 45, 40, and 40 dB HL correctly classified children as having "normal" or "elevated" thresholds. However, due to the lack of air- and bone conduction data in infants with different types and degrees of hearing loss, further ASSR research is needed. PMID- 21034701 TI - Effectiveness of the directional microphone in the Baha(r) DivinoTM. AB - BACKGROUND: Patients with unilateral sensorineural hearing loss (USNHL) experience great difficulty listening to speech in noisy environments. A directional microphone (DM) could potentially improve speech recognition in this difficult listening environment. It is well known that DMs in behind-the-ear (BTE) and custom hearing aids can provide a greater signal-to-noise ratio (SNR) in comparison to an omnidirectional microphone (OM) to improve speech recognition in noise for persons with hearing impairment. Studies examining the DM in bone anchored auditory osseointegrated implants (Baha), however, have been mixed, with little to no benefit reported for the DM compared to an OM. PURPOSE: The primary purpose of this study was to determine if there are statistically significant differences in the mean reception threshold for sentences (RTS in dB) in noise between the OM and DM in the Baha(r) DivinoTM. The RTS of these two microphone modes was measured utilizing two loudspeaker arrays (speech from 0 degrees and noise from 180 degrees or a diffuse eight-loudspeaker array) and with the better ear open or closed with an earmold impression and noise attenuating earmuff. Subjective benefit was assessed using the Abbreviated Profile of Hearing Aid Benefit (APHAB) to compare unaided and aided (Divino OM and DM combined) problem scores. RESEARCH DESIGN: A repeated measures design was utilized, with each subject counterbalanced to each of the eight treatment levels for three independent variables: (1) microphone (OM and DM), (2) loudspeaker array (180 degrees and diffuse), and (3) better ear (open and closed). STUDY SAMPLE: Sixteen subjects with USNHL currently utilizing the Baha were recruited from Washington University's Center for Advanced Medicine and the surrounding area. DATA COLLECTION AND ANALYSIS: Subjects were tested at the initial visit if they entered the study wearing the Divino or after at least four weeks of acclimatization to a loaner Divino. The RTS was determined utilizing Hearing in Noise Test (HINT) sentences in the R-SpaceTM system, and subjective benefit was determined utilizing the APHAB. A three-way repeated measures analysis of variance (ANOVA) and a paired samples t-test were utilized to analyze results of the HINT and APHAB, respectively. RESULTS: Results revealed statistically significant differences within microphone (p < 0.001; directional advantage of 3.2 dB), loudspeaker array (p = 0.046; 180 degrees advantage of 1.1 dB), and better ear conditions (p < 0.001; open ear advantage of 4.9 dB). Results from the APHAB revealed statistically and clinically significant benefit for the Divino relative to unaided on the subscales of Ease of Communication (EC) (p = 0.037), Background Noise (BN) (p < 0.001), and Reverberation (RV) (p = 0.005). CONCLUSIONS: The Divino's DM provides a statistically significant improvement in speech recognition in noise compared to the OM for subjects with USNHL. Therefore, it is recommended that audiologists consider selecting a Baha with a DM to provide improved speech recognition performance in noisy listening environments. PMID- 21034702 TI - Additional data from physicians having previous experience with xylitol as a prophylaxis for acute otitis media in children. PMID- 21034703 TI - [Vitamin D]. PMID- 21034704 TI - [Psoriatic arthritis: what the dermatologist needs to know, Part 2]. AB - This review aims to cover all aspects related to the treatment of psoriatic arthritis and the evaluation of the response to treatment. We define the various evaluation methods currently used to assess response to treatment in patients with psoriatic arthritis and the complementary examination techniques used to ensure adequate follow-up. These tools enable both the dermatologist and the rheumatologist to carry out an ongoing evaluation of the clinical course, severity, and prognosis of the disease. The treatment lines proposed by the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis and the Spanish Society of Rheumatology are discussed. Emerging strategies for treating this condition and improving prognosis are examined. PMID- 21034705 TI - [Pseudofolliculitis barbae]. AB - Pseudofolliculitis barbae is a chronic, irritating, and potentially disfiguring condition that develops as a result of attempts to eliminate hair from the beard area, usually by shaving. It is difficult to determine the incidence of the disorder, but some studies report that it affects up to 1 of every 5 caucasian individuals and that it is much more common in black persons. Clinically it is characterized by the appearance of inflammatory papules and pustules. Once pseudofolliculitis has become established, treatment consists of avoiding shaving and the use of medical treatment similar to that used in acne. However, the long term result is much more dependent on prevention through a correct shaving technique. In severe cases or when a definitive solution is sought, the treatment of choice is photodepilation. PMID- 21034706 TI - [Photodynamic therapy for acne: use of the pulsed dye laser and methylaminolevulinate]. AB - Recent decades have seen the inclusion of acne vulgaris as a potential new indication for photodynamic therapy. Photodynamic therapy and light sources can be considered to be additional tools for primary or adjunctive therapy in patients with recurrent acne or those in whom it is not possible to use other treatments. We investigated the use of pulsed dye laser plus methylaminolevulinate for photodynamic therapy and have performed a comparative study of the use of this laser alone and as an element in photodynamic therapy. PMID- 21034707 TI - [Epidemiology of pediatric dermatologic surgery: a retrospective study of 996 children]. AB - OBJECTIVE: To describe the epidemiology of skin surgery performed in the dermatology department of Hospital Clinico Universitario in Valencia, Spain, on children up to 16 years of age. The study analyzed a 9-year period. MATERIALS AND METHOD: A retrospective review was performed of all tissue excisions and biopsies taken between January 1, 1990, and December 31, 2007, from patients up to 16 years of age seen in the dermatology department of Hospital Clinico Universitario. The following data were collected: age, sex, surgical site, and histopathologic diagnosis. RESULTS: Between 1990 and 2007, 33840 lesions were analyzed histologically; 996 of the lesions (2.94%) were from patients up to 16 years of age, of whom 502 (50.40%) were girls and 484 (49.60%) were boys. The mean age was 11.06 years. The majority (47.39%) of excisions were performed in children of 12 to 16 years. The distribution of the remainder by age groups was as follows: <1 year, 34 excisions (3.41%); >1 to <4 years, 66 (6.63%); >4 to <8 years, 154 (15.46%); and >8 to <12 years, 270 (27.11%). The most common diagnosis was melanocytic nevus (50.20%), followed by pilomatrixoma (4.62%), capillary angioma (3.61%), epidermal cyst (3.61%), Spitz nevus (3.31%), and pyogenic granuloma (3.11%). CONCLUSION: Dermatologic surgery in patients up to 16 years of age accounted for a small percentage of the overall dermatologic surgery in our hospital; the majority of children were in the 12 to <16 year age group. Most children had benign lesions, with melanocytic nevus being by far the most common diagnosis. The majority of lesions were on the trunk, followed by the head and neck. In conclusion, compared with the literature reviewed, ours is the only series on dermatologic surgery in children. It is of interest because it defines the most common conditions in these patients. PMID- 21034708 TI - [Feasibility and reliability of the Spanish version of the Leeds Revised Acne Grading Scale]. AB - BACKGROUND: Although there are more than 25 acne grading systems, there is no consensus on which is most appropriate. Unification of the classifications is recommended in order to facilitate therapeutic decisions. OBJECTIVE: To assess the feasibility and reliability of the Spanish version of the Leeds revised acne grading (LRAG) scale in patients with acne vulgaris in Spain. PATIENTS AND METHODS: We conducted a prospective, multicenter, observational study in Spain, including patients with acne affecting at least 1 of 3 regions: face, back, or chest. Patients were assessed using the LRAG scale and lesion counting. Changes in the scores were determined at 4-6 weeks, and were correlated with the lesion count. Physicians were asked 4 questions regarding difficulty using the scale and the time employed. RESULTS: A total of 259 sites of acne were assessed in 239 patients at 57 centers. The majority of physicians (89.5%) stated that the LRAG scale was not difficult to use. The mean administration time was 3.12min. Cross sectional validity (P<.012 for the face, P<.001 for the back and chest), longitudinal validity (P<.0001 for the face, back, and chest), and intraobserver and interobserver reliability (Cronbach alpha >0.8) were significant for inflammatory lesions in all regions. Sensitivity to change was demonstrated for lesions in all regions, based on the correlation between the difference in severity and the number of lesions recorded by the LRAG, and the difference in the lesion count between baseline and follow-up. CONCLUSION: The Spanish version of the LRAG scale is a practical and reliable tool and is sensitive to change. It is a valid tool for the objective assessment of the severity of acne. PMID- 21034709 TI - [Plaque-phase mycosis fungoides treated with photodynamic therapy: results from 12 patients]. AB - BACKGROUND: Recent years have seen an increase in the off-label use of photodynamic therapy for the treatment of a variety of skin diseases. Plaque phase mycosis fungoides is among the most promising possibilities for the use of this treatment. OBJECTIVES: To evaluate the treatment of plaque-phase mycosis fungoides with photodynamic therapy and compare the results obtained using fluorescence photography. MATERIALS AND METHODS: We performed a prospective, descriptive, observational study. Twelve patients with 24 lesions were treated with topical methyl aminolevulinate (MAL) under an occlusive dressing for 3 h, followed by 8 min of red light (630 nm, 37 J/cm2; Aktilite). RESULTS: Six patients had a complete response, 5 a partial response, and 1 did not respond to treatment. A mean of 5.7 sessions was applied and no side effects were reported. Treatment tolerance was excellent. CONCLUSIONS: Photodynamic therapy with MAL appears to be a good treatment option for patients with plaque-phase mycosis fungoides with a small number of lesions. PMID- 21034710 TI - [Acquired progressive lymphangioma (benign lymphangioendothelioma)]. AB - Acquired progressive lymphangioma is a rare vascular tumor with a locally aggressive behavior. Histologically it is characterized by a proliferation of numerous, dilated, thin-walled vessels lined by flat endothelial cells with no nuclear atypia. The vessels appear to dissect between the collagen fibers. It usually presents as an asymptomatic, slow-growing, reddish-brown plaque. We present the case of a 32-year-old man with acquired progressive lymphangioma. The tumor was in the hypogastric region and had arisen on a congenital vascular lesion previously diagnosed as multifocal cutaneous angiomatosis. It was very painful and impeded walking, for which reason it was decided to perform excision. Dermatologists and pathologists must be aware of acquired progressive lymphangioma as early surgical treatment, while the lesion is still small, is curative and prevents subsequent complications due to growth. PMID- 21034711 TI - [Flat papules on the lip of a young adult]. PMID- 21034712 TI - [Linear keratotic plaques on both hands]. PMID- 21034713 TI - [Acral pustules as the key manifestation in the diagnosis of subacute infective endocarditis]. PMID- 21034714 TI - [Management of basal cell carcinoma with perineural invasion]. PMID- 21034715 TI - [Psoriasis following contact with rubber gloves in a patient sensitized to rubber additives]. PMID- 21034716 TI - [Mucoepidermoid carcinoma of the lip]. PMID- 21034717 TI - [Primary cutaneous CD30+ large T-Cell lymphoma with lymph node and cerebral metastases]. PMID- 21034718 TI - [Poliosis and status epilepticus as the presentation of tuberous sclerosis in an infant]. PMID- 21034719 TI - [Erythema elevatum diutinum or extrafacial granuloma faciale?]. PMID- 21034721 TI - Urban-rural differences of age- and species-specific campylobacteriosis incidence, Hesse, Germany, July 2005 - June 2006. AB - Campylobacter infection is the most common cause of bacterial gastroenteritis worldwide. This study examines the association between campylobacteriosis incidence and degree of urbanicity in Hesse, Germany, by age and Campylobacter species. During a one-year period (July 2005-June 2006), Hessian local health authorities provided information on municipality of residence for 3,315 campylobacteriosis cases. We calculated age- and Campylobacter species-specific incidences for six levels of urbanicity, as defined by population density and accessibility of centres. For children under five years old, living in inner rural areas (incidence rate ratio (IRR): 2.9; 95% confidence interval (CI): 1.9 to 4.4) and for children aged 5-14 years living in inner rural (IRR: 2.1; 95% CI: 1.3 to 3.1) or intermediate areas (inner intermediate area IRR: 1.8; 95% CI: 1.2 to 2.7; outer intermediate area IRR: 2.1; 95% CI: 1.3 to 3.3) was associated with a statistically significantly higher campylobacteriosis risk (reference category: inner urban area). Calculations by Campylobacter species showed a higher risk of gastroenteritis due to C. coli for inhabitants (all ages) of non-urban areas. This study suggests that differences in risk factors by age, Campylobacter species and degree of urbanicity do exist. For children contact with animals or the environment may be responsible for a substantial proportion of sporadic Campylobacter infections. PMID- 21034722 TI - A new pandemic influenza A(H1N1) genetic variant predominated in the winter 2010 influenza season in Australia, New Zealand and Singapore. AB - Pandemic H1N1 influenza virus is of global health concern and is currently the predominant influenza virus subtype circulating in the southern hemisphere 2010 winter. The virus has changed little since it emerged in 2009, however, in this report we describe several genetically distinct changes in the pandemic H1N1 influenza virus. These variants were first detected in Singapore in early 2010 and have subsequently spread through Australia and New Zealand. At this stage, these signature changes in the haemagglutinin and neuraminidase proteins have not resulted in significant antigenic changes which might make the current vaccine less effective, but such adaptive mutations should be carefully monitored as the northern hemisphere approaches its winter influenza season. PMID- 21034723 TI - A community outbreak of Legionnaires' disease in South Wales, August-September 2010. AB - During August and September 2010, an outbreak comprising 22 cases of Legionnaires' disease was identified by the public health service in Wales. The cases are distributed over a wide geographical area in South East Wales. There are two space-time clusters centred on the upper Rhymney Valley and the lower Cynon Valley respectively. Epidemiological investigations are compatible with cooling towers in each location as the potential source, but environmental inspections were satisfactory and microbiological investigations are inconclusive. PMID- 21034724 TI - Adipose tissue-derived stem cells secrete CXCL5 cytokine with chemoattractant and angiogenic properties. AB - Adipose tissue-derived stem cells (ADSC) secreted CXCL5 cytokine abundantly and higher passaged ADSC up to passage 6 (P6) secreted more CXCL5 than lower passaged ADSC. Higher passaged ADSC also appeared to express higher levels of CXCL5 receptor, i.e., CXCR2. Both CXCL5 and CXCR2 were localized in the tunica intima and tunica adventitia of blood vessels in adipose tissue. Colocalization with CD34 further indicates their association with the putative ADSC in tunica adventitia. Migration assay indicates chemoattractant effects of CXCL5 on ADSC and HUVEC endothelial cells. CXCL5 also enhanced matrigel-based endothelial tube like formation of HUVEC. PMID- 21034725 TI - Spontaneous and visible light-induced ultraweak photon emission from rat eyes. AB - Here, we present the first experimental in vitro evidence of the existence of spontaneous and visible light-induced ultraweak photon emission from freshly isolated whole eye, lens, vitreous humor, and retina samples from rats. These results suggest that the photochemical source of retinal discrete noise, as well as retinal phosphenes, may originate from natural bioluminescent photons within the eyes. During normal vision, the eyes are continuously exposed to ambient powerful photons that pass through various parts of the eyes, which can produce ultraweak delayed bioluminescent photons that arise from diverse parts of the eyes. Although the importance and possible role of ambient light-induced permanent delayed photons (within different parts of the eyes) during vision requires further investigation, our study may provide evidence of an origin of discrete dark noise and retinal phosphenes. PMID- 21034726 TI - Comparison of modification sites formed on human serum albumin at various stages of glycation. AB - BACKGROUND: Many of the complications encountered during diabetes can be linked to the non-enzymatic glycation of proteins, including human serum albumin (HSA). However, there is little information regarding how the glycation pattern of HSA changes as the total extent of glycation is varied. The goal of this study was to identify and conduct a semi-quantitative comparison of the glycation products on HSA that are produced in the presence of various levels of glycation. METHODS: Three glycated HSA samples were prepared in vitro by incubating physiological concentrations of HSA with 15 mmol/l glucose for 2 or 5 weeks, or with 30 mmol/l glucose for 4 weeks. These samples were then digested and examined by matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) to identify the glycation products that were formed. RESULTS: It was found that the glycation pattern of HSA changed with its overall extent of total glycation. Many modifications including previously-reported primary glycation sites (e.g., K199, K281, and the N-terminus) were consistently found in the tested samples. Lysines 199 and 281, as well as arginine 428, contained the most consistently identified and abundant glycation products. Lysines 93, 276, 286, 414, 439, and 524/525, as well as the N-terminus and arginines 98, 197, and 521, were also found to be modified at various degrees of HSA glycation. CONCLUSIONS: The glycation pattern of HSA was found to vary with different levels of total glycation and included modifications at the 2 major drug binding sites on this protein. This result suggests that different modified forms of HSA, both in terms of the total extent of glycation and glycation pattern, may be found at various stages of diabetes. The clinical implication of these results is that the binding of HSA to some drug may be altered at various stages of diabetes as the extent of glycation and types of modifications in this protein are varied. PMID- 21034727 TI - Effects of shampoo and water washing on hair cortisol concentrations. AB - BACKGROUND: Measurement of cortisol in hair is an emerging biomarker for chronic stress in human and nonhuman primates. Currently unknown, however, is the extent of potential cortisol loss from hair that has been repeatedly exposed to shampoo and/or water. METHODS: Pooled hair samples from 20 rhesus monkeys were subjected to five treatment conditions: 10, 20, or 30 shampoo washes, 20 water-only washes, or a no-wash control. For each wash, hair was exposed to a dilute shampoo solution or tap water for 45 s, rinsed 4 times with tap water, and rapidly dried. Samples were then processed for cortisol extraction and analysis using previously published methods. RESULTS: Hair cortisol levels were significantly reduced by washing, with an inverse relationship between number of shampoo washes and the cortisol concentration. This effect was mainly due to water exposure, as cortisol levels following 20 water-only washes were similar to those following 20 shampoo treatments. CONCLUSIONS: Repeated exposure to water with or without shampoo appears to leach cortisol from hair, yielding values that underestimate the amount of chronic hormone deposition within the shaft. Collecting samples proximal to the scalp and obtaining hair washing frequency data may be valuable when conducting human hair cortisol studies. PMID- 21034728 TI - MDM2-related responses in 3T3-L1 adipocytes exposed to cooling and subsequent rewarming. AB - Insulin-like growth factor-I and insulin induce the production of phospho-Ser-166 MDM2, a target of Akt, and influence the formation of the MDM2 complex. The glycolipid hormone insulin differentially activates phosphatidylinositol 3-kinase (PI3K)/Akt pathways in 3T3-L1 (L1) adipocytes incubated at 19 degrees C. Responses of L1 adipocytes to different temperature changes and their regulatory mechanisms are poorly understood. We exposed L1 adipocytes to cooling and subsequent rewarming in the presence or absence of wortmannin, a PI3K inhibitor, or mithramycin A, a transcription inhibitor, and examined the induction of phospho-Ser-166 MDM2 and MDM2 and the subcellular formation of the MDM2 complex using western blot analysis. Exposure to 28 and 18 degrees C induced phospho MDM2 in cells and increased the level of MDM2 in the plasma membrane of cells. These temperatures did not affect the total MDM2 level. Similar results were obtained when the cells were treated with insulin. Exposure to 4 degrees C increased the total MDM2 level and did not induce phospho-MDM2, which was induced by rewarming at 37 degrees C after cooling at 4 degrees C without any alteration in the protein level. Mithramycin A (10 MUM) did not alter the increase in protein level induced at 4 degrees C. The induction of phospho-molecules at 28 and 18 degrees C was impaired slightly by 1 MUM of wortmannin but not by 0.1 MUM of wortmannin. This low concentration of wortmannin completely blocked the induction of phospho-MDM2 by rewarming. Our results indicate that temperature changes induce MDM2-related responses, including those that are stimulated by receptor responses and dependent on a kinase inhibitor, in L1 adipocytes. PMID- 21034729 TI - The C. elegans MAGI-1 protein is a novel component of cell junctions that is required for junctional compartmentalization. AB - Cell junctions are essential to maintain polarity and tissue integrity. Epithelial cell junctions are composed of distinct sub-compartments that together ensure the strong adhesion between neighboring cells. In Caenorhabditis elegans epithelia, the apical junction (CeAJ) forms a single electron-dense structure, but at the molecular level it is composed of two sub-compartments that function redundantly and localize independently as two distinct but adjacent circumferential rings on the lateral plasma membrane. While investigating the role of the multi PDZ-domain containing protein MAGI-1 during C. elegans epidermal morphogenesis, we found that MAGI-1 localizes apical to both the Cadherin/Catenin (CCC) and AJM-1/DLG-1 (DAC) containing sub-domains. Removal of MAGI-1 function causes a loss of junctional compartmentalization along the lateral membrane and reduces the overall robustness of cell-cell adhesion mediated by either type of cell junctions. Our results suggest that MAGI-1 functions as an "organizer" that ensures the correct segregation of different cell adhesion complexes into distinct domains along the lateral plasma membrane. Thus, the formation of stable junctions requires the proper distribution of the CCC and DAC adhesion protein complexes along the lateral plasma membrane. PMID- 21034730 TI - Insect Tc-six4 marks a unit with similarity to vertebrate placodes. AB - Cranial placodes are specialized ectodermal regions in the developing vertebrate head that give rise to both neural and non-neural cell types of the neuroendocrine system and the sense organs of the visual, olfactory and acoustic systems. The cranial placodes develop from a panplacodal region which is specifically marked by genes of the eyes absent/eya and two "six homeobox" family members (sine oculis/six1 and six4). It had been believed that cranial placodes are evolutionary novelties of vertebrates. However, data from non-vertebrate chordates suggest that placode-like structures evolved in the chordate ancestor already. Here, we identify a morphological structure in the embryonic head of the beetle Tribolium castaneum with placode-like features. It is marked by the orthologs of the panplacodal markers Tc-six4, Tc-eya and Tc-sine oculis/six1 (Tc six1) and expresses several genes known to be involved in adenohypophyseal placode development in vertebrates. Moreover, it contributes to both epidermal and neural tissues. We identify Tc-six4 as a specific marker for this structure that we term the insect head placode. Finally, we reveal the regulatory gene network of the panplacodal genes Tc-six4, Tc-eya and Tc-six1 and identify them as head epidermis patterning genes. Our finding of a placode-like structure in an insect suggests that a placode precursor was already present in the last common ancestor of bilaterian animals. PMID- 21034731 TI - The cell adhesion-associated protein Git2 regulates morphogenetic movements during zebrafish embryonic development. AB - Signaling through cell adhesion complexes plays a critical role in coordinating cytoskeletal remodeling necessary for efficient cell migration. During embryonic development, normal morphogenesis depends on a series of concerted cell movements; but the roles of cell adhesion signaling during these movements are poorly understood. The transparent zebrafish embryo provides an excellent system to study cell migration during development. Here, we have identified zebrafish git2a and git2b, two new members of the GIT family of genes that encode ArfGAP proteins associated with cell adhesions. Loss-of-function studies revealed an essential role for Git2a in zebrafish cell movements during gastrulation. Time lapse microscopy analysis demonstrated that antisense depletion of Git2a greatly reduced or arrested cell migration towards the vegetal pole of the embryo. These defects were rescued by expression of chicken GIT2, indicating a specific and conserved role for Git2 in controlling embryonic cell movements. Git2a knockdown embryos showed defects in cell morphology that were associated with reduced cell contractility. We show that Git2a is required for phosphorylation of myosin light chain (MLC), which regulates myosin II-mediated cell contractility. Consistent with this, embryos treated with Blebbistatin-a small molecule inhibitor for myosin II activity-exhibited cell movement defects similar to git2a knockdown embryos. These observations provide in vivo evidence of a physiologic role for Git2a in regulating cell morphogenesis and directed cell migration via myosin II activation during zebrafish embryonic development. PMID- 21034732 TI - A cluster of non-redundant Ngn1 binding sites is required for regulation of deltaA expression in zebrafish. AB - Proneural genes encode bHLH transcription factors that are key regulator of neurogenesis in both vertebrates and invertebrates. How these transcription factors regulate targets required for neural determination and/or specification is beginning to be understood. In this study, we show that zebrafish deltaA is a transcriptional target of proneural factors. Using a combination of transient and stable transgenic reporters, we show that regulation of deltaA by one such proneural factor, Ngn1, requires three clustered E-box binding sites that act in a non-redundant manner. Furthermore, we show that as for other proneural targets, members of the different proneural families regulate deltaA expression via distinct cis-regulatory modules (CRMs). Interestingly, however, while the deltaA CRM regulated by a second proneural factor, Ascl1, has been conserved between delta genes of different species, we show that the Ngn1 CRM has not. These results suggest that evolutionary constraints on the mechanism by which Ngn1 regulates gene expression appear less strict than for Ascl1. PMID- 21034733 TI - BmprIa is required in mesenchymal tissue and has limited redundant function with BmprIb in tooth and palate development. AB - The BMP signaling plays a pivotal role in the development of craniofacial organs, including the tooth and palate. BmprIa and BmprIb encode two type I BMP receptors that are primarily responsible for BMP signaling transduction. We investigated mesenchymal tissue-specific requirement of BmprIa and its functional redundancy with BmprIb during the development of mouse tooth and palate. BmprIa and BmprIb exhibit partially overlapping and distinct expression patterns in the developing tooth and palatal shelf. Neural crest-specific inactivation of BmprIa leads to formation of an unusual type of anterior clefting of the secondary palate, an arrest of tooth development at the bud/early cap stages, and severe hypoplasia of the mandible. Defective tooth and palate development is accompanied by the down regulation of BMP-responsive genes and reduced cell proliferation levels in the palatal and dental mesenchyme. To determine if BmprIb could substitute for BmprIa during tooth and palate development, we expressed a constitutively active form of BmprIb (caBmprIb) in the neural crest cells in which BmprIa was simultaneously inactivated. We found that substitution of BmprIa by caBmprIb in neural rest cells rescues the development of molars and maxillary incisor, but the rescued teeth exhibit a delayed odontoblast and ameloblast differentiation. In contrast, caBmprIb fails to rescue the palatal and mandibular defects including the lack of lower incisors. Our results demonstrate an essential role for BmprIa in the mesenchymal component and a limited functional redundancy between BmprIa and BmprIb in a tissue-specific manner during tooth and palate development. PMID- 21034734 TI - Cisplatin-induced cardiotoxicity: Mechanisms and cardioprotective strategies. AB - Increased oxidative stress and apoptosis have been implicated in the cardiotoxicity that limits the clinical use of cisplatin as an anti-tumoral drug. Our study was conducted to evaluate the protective potential of acetyl-l carnitine, DL-alpha-lipoic acid and silymarin against cisplatin-induced myocardial injury. Eighty male albino rats were divided into eight groups. The first four groups were treated with normal saline, acetyl-l-carnitine (500mg/kg, i.p.), DL-alpha-lipoic acid (100mg/kg, p.o.) and silymarin (100mg/kg, p.o.) respectively, for 10 successive days. The remaining groups were treated with the same doses of normal saline, acetyl-l-carnitine, DL-alpha-lipoic acid and silymarin, respectively, for 5 successive days before and after a single dose of cisplatin (10mg/kg, i.p.). Serum activities of lactate dehydrogenase (LDH), creatine kinase (CK), creatine kinase isoenzyme MB (CK-MB) and plasma cardiac troponin I (cTnI) concentration were estimated. Malondialdehyde (MDA), reduced glutathione (GSH) contents, superoxide dismutase activity (SOD) and protein content in cardiac tissues were measured. Moreover, integrity of both mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) was also examined. Cisplatin treated rats experienced a significant elevation of serum activities of LDH, CK, CK-MB and cTnI plasma concentration. These effects were accompanied by a significant increase in MDA level. On the other hand, a significant decrease in GSH content, SOD activity and total protein content was observed. In addition, both mtDNA and nDNA were heavily damaged. However, acetyl-l-carnitine, DL-alpha lipoic acid and silymarin significantly attenuated the cisplatin-evoked disturbances in the above-mentioned parameters. In conclusion, the former drugs were proven to be potential candidates to ameliorate cisplatin-induced cardiotoxicity. PMID- 21034735 TI - Differential recruitment of high affinity A1 and A2A adenosine receptors in the control of colonic neuromuscular function in experimental colitis. AB - This study investigated the expression of A(1) and A(2A) receptors in the rat colonic neuromuscular compartment, and characterized their roles in the control of motility during inflammation. Colitis was induced by 2,4 dinitrobenzenesulfonic acid. A(1), A(2A) receptors, and ecto-5'-nucleotidase (CD73, adenosine producing enzyme) mRNA expression was examined by RT-PCR. The effects of DPCPX (A(1) receptor antagonist), CCPA (A(1) receptor agonist), 4-(2 [7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol (A(2A) receptor antagonist), 4-[2-[[6-amino-9-(N-ethyl-b-D-ribofuranuronamidosyl) 9H-purin-2-yl]amino]ethyl]benzenepropanoic acid hydrochloride (A(2A) receptor agonist), AOPCP (CD73 inhibitor) were tested on electrically or carbachol-evoked contractions in colonic longitudinal muscle preparations. In normal colon, RT-PCR revealed the presence of A(1) receptors, A(2A) receptors and CD73, and an increased expression of A(2A) receptors and CD73 was detected in inflamed tissues. In normal colon, DPCPX or 4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3 a][1,3,5]triazin-5-ylamino]ethyl)phenol enhanced electrically-induced contractions, while in inflamed preparations the effect of DPCPX no longer occurred. In normal colon, CCPA or 4-[2-[[6-amino-9-(N-ethyl-b-D ribofuranuronamidosyl)-9H-purin-2-yl]amino]ethyl] benzenepropanoic acid hydrochloride decreased electrically-induced contractions. Under inflammation, 4 [2-[[6-amino-9-(N-ethyl-b-D-ribofuranuronamidosyl)-9H-purin-2-yl]amino]ethyl] benzenepropanoic acid hydrochloride reduced electrically evoked contractions with higher efficacy, while the inhibition by CCPA remained unchanged. A(1) and A(2A) receptor ligands did not affect carbachol-induced contractions. AOPCP enhanced electrically-induced contractions and prevented the contractile effects of 4-(2 [7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol, without interfering with DPCPX, both in normal and inflamed colons. These results indicate that, in normal colon, both A(1) and A(2A) receptors contribute to the inhibitory control of motor functions at neuronal level. Under bowel inflammation, A(1) receptor loses its modulating actions, while the recruitment of A(2A) receptor by CD73-dependent endogenous adenosine drives an enhanced inhibitory control of colonic neuromotility. PMID- 21034736 TI - Effects of montelukast, a cysteinyl-leukotriene type 1 receptor antagonist, on the pathogenesis of bleomycin-induced pulmonary fibrosis in mice. AB - Cysteinyl-leukotrienes are potent mediators involved in various inflammatory diseases and lung disorders such as asthma. However, their precise role in the pathogenesis of pulmonary fibrosis is unknown. In the present study, we investigated the effect of montelukast, a cysteinyl-leukotriene type 1 receptor antagonist, on bleomycin-induced pulmonary fibrosis in mice. Montelukast (10mg/kg/day) was orally administered to the bleomycin-induced pulmonary fibrosis mice for 3days before and 14days after intratracheal instillation of bleomycin. We evaluated the effects of montelukast on the development of pulmonary fibrosis in these mice and investigated the expression of various cytokines and two cysteinyl-leukotriene receptors. Treatment with montelukast significantly attenuated the increased fibrotic area and hydroxyproline content in the fibrotic lungs of bleomycin-instilled mice. Montelukast treatment also decreased mRNA levels of IL-6, IL-10, IL-13, and TGF-beta1, all of which were elevated in fibrotic lungs. In fibrotic lungs, TNF-alpha and IL-1beta mRNA levels were increased and IFN-gamma mRNA levels were decreased, but montelukast did not affect these mRNA levels. Furthermore, cysteinyl-leukotriene type 1 receptor mRNA levels were increased, whereas cysteinyl-leukotriene type 2 receptor mRNA levels were decreased in fibrotic lungs. Montelukast treatment induced the recovery of cysteinyl-leukotriene type 2 receptor mRNA levels to normal control levels but did not change cysteinyl-leukotriene type 1 receptor mRNA levels. These results suggest that montelukast exhibits its beneficial effects by inhibiting the overexpression of IL-6, IL-10, IL-13, and TGF-beta1 and by modulating the homeostatic balance between the cysteinyl-leukotriene type 1 and type 2 receptors. PMID- 21034737 TI - Low dose of bupropion significantly enhances the anticonvulsant activity of felbamate, lamotrigine and topiramate in mice. AB - Experimental evidence indicates that bupropion hydrochloride, an antidepressant and a first-line smoking cessation aid, exerts dose-dependently anticonvulsant and convulsant effects. In this study, chronic bupropion pretreatment intraperitoneally (i.p.) for 14 days in a dose of 5 mg/kg reduced the ED(50) (i.e. the dose protecting 50% of mice against electroconvulsions) of lamotrigine, topiramate, and felbamate from 4.58, 60.95, and 48.79 (antiepileptic+vehicle) to 3.01, 41.68, and 37.28 mg/kg (antiepileptic+bupropion), respectively, against maximal electroshock-induced seizures in mice. Bupropion significantly increased the plasma and brain concentrations of lamotrigine. Plasma concentration of topiramate was elevated, however, the brain concentration of the drug was not affected. Neither plasma nor brain concentrations of felbamate were elevated by bupropion administration. Bupropion did not exacerbate motor coordination impairment caused by the antiepileptic drugs in the rotarod test. Chronic administration of bupropion significantly potentiates the protective activity of lamotrigine, topiramate, and felbamate against maximal electroshock-induced seizures. A pharmacokinetic interaction is responsible for the effect of bupropion co-administered with lamotrigine. PMID- 21034738 TI - Muscarinic acetylcholine receptors in the nucleus accumbens core and shell contribute to cocaine priming-induced reinstatement of drug seeking. AB - Muscarinic acetylcholine receptors in the nucleus accumbens play an important role in mediating the reinforcing effects of cocaine. However, there is a paucity of data regarding the role of accumbal muscarinic acetylcholine receptors in the reinstatement of cocaine-seeking behavior. The goal of these experiments was to assess the role of muscarinic acetylcholine receptors in the nucleus accumbens core and shell in cocaine and sucrose priming-induced reinstatement. Rats were initially trained to self-administer cocaine or sucrose on a fixed-ratio schedule of reinforcement. Lever-pressing behavior was then extinguished and followed by a subsequent reinstatement phase during which operant responding was induced by either a systemic injection of cocaine in cocaine-experienced rats or non contingent delivery of sucrose pellets in subjects with a history of sucrose self administration. Results indicated that systemic administration of the muscarinic acetylcholine receptor antagonist scopolamine (5.0 mg/kg, i.p.) dose-dependently attenuated cocaine, but not sucrose, reinstatement. Furthermore, administration of scopolamine (36.0 MUg) directly into the nucleus accumbens shell or core attenuated cocaine priming-induced reinstatement. In contrast, infusion of scopolamine (36.0 MUg) directly into the accumbens core, but not shell, attenuated sucrose reinstatement, which suggests that muscarinic acetylcholine receptors in these two subregions of the nucleus accumbens have differential roles in sucrose seeking. Taken together, these results indicate that cocaine priming-induced reinstatement is mediated, in part, by increased signaling through muscarinic acetylcholine receptors in the shell subregion of the nucleus accumbens. Muscarinic acetylcholine receptors in the core of the accumbens, in contrast, appear to play a more general (i.e. not cocaine specific) role in motivated behaviors. PMID- 21034739 TI - Hyperactivity of the hypothalamus-pituitary-adrenal axis in lipopolysaccharide induced neurodevelopmental model of schizophrenia in rats: effects of antipsychotic drugs. AB - Recent data indicate that a significant number of schizophrenic patients are hypercortisolemic and that glucocorticoids are involved in the pathogenesis of schizophrenia. The aim of the present study was to evaluate whether behavioural schizophrenia-like changes in the lipopolysaccharide (LPS)-induced neurodevelopmental model of this brain disorder are associated with alterations in the level of plasma corticosterone, the concentration of glucocorticoid receptors and the amount of the immunophilin FKBP51, the glucocorticoid receptor co-chaperone, in the hippocampus and frontal cortex. We found that the adult offspring of prenatally LPS-treated rats showed a deficit in prepulse inhibition (PPI), an enhancement of amphetamine-induced locomotor activity, an elevated plasma level of corticosterone and a decrease in both the glucocorticoid receptor level in the hippocampus and the FKBP51 concentration in the frontal cortex. Most of these changes were reversed by the atypical antipsychotic drug clozapine, whereas chlorpromazine had no effect on PPI but attenuated the amphetamine induced hyperactivity and normalised the hippocampal level of glucocorticoid receptors. The changes in the level of plasma corticosterone and cortical FKBP51 were attenuated by chlorpromazine in female offspring only. This study supports the hypothesis of hypothalamic-pituitary-adrenal (HPA) axis hyperactivity in schizophrenia and suggests that this hyperactivity results from a decrease in the hippocampal glucocorticoid receptor level and a decrease in FKBP51 in the frontal cortex. PMID- 21034740 TI - Pharmacological characterization of the ghrelin receptor antagonist, GSK1614343 in rat RC-4B/C cells natively expressing GHS type 1a receptors. AB - A novel growth hormone secretagogues type 1a (GHS1a) receptors antagonist (2R)-N' [3,5- bis(trifluoromethyl)phenyl]-2-[(8aR)-hexahydropyrrolo[1,2-a]pyrazin-2(1H) yl]-2-(3- pyridinyl)ethanohydrazide (GSK1614343) was functionally characterised in rat pituitary adenoma cell line, RC-4B/C endogenously expressing GHS1a receptors. The antagonism profile of GSK1614343 was compared with that of 6-[(4 fluorophenyl)oxy]-2-methyl-3-{[(3S)-1-(1-methylethyl)-3- piperidinyl]methyl} 4(3H)-quinazolinone (YIL-781) another ghrelin receptor antagonist recently published. The activity of both compounds was also evaluated at rat recombinant GHS1a receptors. The characterization of the two antagonists was performed by intracellular calcium mobilization measurements by using fluorometric imaging plate reader (FLIPR) technology and inositol phosphate (IP) turnover measurements by [3H]-IP accumulation assay. RC-4B/C and U2-OS cells transiently transduced with rat GHS1a receptors virus were used. In RC-4B/C cells, GSK1614343 and YIL 781, depressed the ghrelin maximal response in FLIPR assay as result of hemi equilibria phenomenon. When using the [3H]-IP accumulation assay both compounds behaved as competitive antagonist with pKB values of 8.03 for GSK1614343 and 7.54 for YIL-781. In rat recombinant receptor, GSK1614343 and YIL-781 inhibited the calcium response induced by ghrelin with pIC50 values of 7.90 and 8.27, respectively. GSK1614343 and YIL-781 did not show intrinsic activity in both endogenously expressed and recombinant rat GHS1a receptors. The new ghrelin receptor antagonist GSK1614343 is a potent competitive antagonist in rat pituitary RC-4B/C cells endogenously expressing GHS1a receptors when equilibrium conditions between ligand and receptor are reached in the test assay. GSK1614343 represents a useful tool to investigate the physiological relevance of the ghrelin system in rat models. PMID- 21034741 TI - A novel coenzyme A:diacylglycerol acyltransferase 1 inhibitor stimulates lipid metabolism in muscle and lowers weight in animal models of obesity. AB - Obesity is characterized by the accumulation of triacylglycerol in adipocytes. Coenzyme A:diacylglycerol acyltransferase 1 (DGAT1) is one of two known DGAT enzymes that catalyze the final and only committed step in triacylglycerol synthesis. In this report, we describe the pharmacological effects of a novel selective DGAT1 inhibitor, Compound-A. This compound inhibited triacylglycerol synthesis in both adipocytes and skeletal myotubes, and increased fatty acid oxidation in skeletal myotubes at 1 MUM. The repeated administration of Compound A to diet-induced obese C57BL/6J and genetically obese KKA(y) mice (3-30 mg/kg for 3-4 weeks) significantly decreased the visceral fat pad weights and the hepatic lipid contents compared to controls without affecting food intake. In addition, fatty acid oxidation in skeletal muscle tissues was increased by the treatment of Compound-A in both mice strains. This is the first report demonstrating that a small synthetic DGAT1 inhibitor increases fatty acid oxidation in skeletal muscle in vitro and ex vivo. These results suggest that DGAT1 inhibition is a promising therapeutic approach for the treatment of obesity and lipid abnormalities such as hepatic steatosis. PMID- 21034743 TI - MDM2 promotes cell motility and invasiveness through a RING-finger independent mechanism. AB - Recent studies connect MDM2 with increased cell motility, invasion and/or metastasis proposing an MDM2-mediated ubiquitylation-dependent mechanism. Interestingly, in renal cell carcinoma (RCC) p53/MDM2 co-expression is associated with reduced survival which is independently linked with metastasis. We therefore investigated whether expression of p53 and/or MDM2 promotes aggressive cell phenotypes. Our data demonstrate that MDM2 promotes increased motility and invasiveness in RCC cells (N.B. similar results are obtained in non-RCC cells). This study shows for the first time both that endogenous MDM2 significantly contributes to cell motility and that this does not depend upon the MDM2 RING finger, i.e. is independent of ubiquitylation (and NEDDylation). Our data suggest that protein-protein interactions provide a likely mechanistic basis for MDM2 promoted motility which may constitute future therapeutic targets. PMID- 21034742 TI - Inhibition of the JNK/Bim pathway by Hsp70 prevents Bax activation in UV-induced apoptosis. AB - Here we studied the mechanism by which heat shock protein 70 (Hsp70) prevents Bax activation during ultraviolet (UV)-induced apoptosis. UV treatment led to c-Jun N terminal kinase (JNK) phosphorylation, Bim redistribution and subsequent Bax activation. Bim depletion caused a smaller reduction in apoptosis than that by JNK inhibition, indicating that Bim activation is not entirely responsible for induction of apoptosis and other mechanisms are involved. Hsp70 knockdown resulted in high levels of activated JNK and Bax, while Hsp70 overexpression inhibited these processes. These findings demonstrate that Hsp70 prevented Bax activation via inhibiting the JNK/Bim pathway. Simultaneously, increased binding of Hsp70 to Bax was observed. Collectively, our results for the first time demonstrate that Hsp70 prevents Bax activation both by inhibiting the JNK/Bim pathway and by interacting with Bax in UV-induced apoptosis. PMID- 21034744 TI - Telaprevir is effective given every 8 or 12 hours with ribavirin and peginterferon alfa-2a or -2b to patients with chronic hepatitis C. AB - BACKGROUND & AIMS: Recent studies have shown that 12 weeks of treatment with telaprevir, administered every 8 hours (q8h), combined with pegylated interferon (peginterferon) alfa-2a plus ribavirin significantly increased the rate of hepatitis C virus (HCV) eradication (sustained virologic response [SVR]) in patients infected with HCV genotype 1 compared with approved therapy. We investigated the efficacy, safety, tolerability, and pharmacokinetics of telaprevir given q8h or every 12 hours (q12 h) in combination with peginterferon alfa-2a or alfa-2b. METHODS: Treatment-naive patients (n = 161) infected with HCV genotype 1 were randomly assigned to groups that were given open-label telaprevir (750 mg q8 h or 1125 mg q12 h) in combination with standard doses of peginterferon alfa-2a (180 MUg/wk) and ribavirin (1000-1200 mg/day) or peginterferon alfa-2b (1.5 MUg.kg(-1).wk(-1)) and ribavirin (800-1200 mg/day). Patients received triple therapy for 12 weeks, followed by 12 or 36 additional weeks of treatment with peginterferon alfa and ribavirin, based on virologic response. RESULTS: Baseline characteristics were similar for all groups. SVR rates were 81.0% to 85.0% among groups; most patients received 24 weeks of therapy (68.0%). There were no significant differences in SVR rates (intent-to treat analysis) among groups (P >= .787), between the pooled q8 h and q12 h groups (P = .997), or between the pooled peginterferon alfa-2a/ribavirin and peginterferon alfa-2b/ribavirin groups (P = .906). The safety profile was similar among all groups. CONCLUSIONS: A high proportion (>80%) of patients achieved an SVR regardless of the telaprevir dosing frequency (q8 h or q12 h) or type of peginterferon alfa used (alfa-2a or alfa-2b). PMID- 21034745 TI - Effects of transgenic Bt cotton on overwintering characteristics and survival of Helicoverpa armigera. AB - The effects of transgenic Bt cotton on the overwintering generation of the cotton bollworm, Helicoverpa armigera (Hubner) (Lepidoptera: Noctuidae), are unknown. We hypothesized that a Bt cotton diet may adversely affect fitness of this generation and examined fresh weight, lipids, glycogens, low-molecular-weight sugars and SCPs (supercooling points) of pupae, as well as survival of larvae, diapausing pupae and adult emergence in comparison with controls. Field and laboratory experiments showed that larvae fed on Bt cotton had a decreased pupation rate, and fewer entered diapause and emerged as adults compared with larvae fed non-Bt cotton. Furthermore, larvae fed Bt cotton had reduced pupal weight, glycogen content and trehalose levels both in diapausing and in non diapausing pupae, and only diapausing pupae had an increased SCP compared to controls. The SCPs of diapausing pupae reared on Bt cotton were significantly higher than those reared on non-Bt cotton. The trehalose levels of diapausing pupae reared on Bt cotton were significantly lower than those of larvae reared on non-Bt cotton. Thus, these results suggest that a Bt cotton diet weakens the preparedness of cotton bollworm for overwintering and reduces survival of the overwintering generation, which will in turn reduce the density of the first generation in the following year. Effects of transgenic Bt cotton on the overwintering generation of cotton bollworm appear to have significantly contributed to the suppression of cotton bollworm observed throughout northern China in the past decade. PMID- 21034746 TI - Centchroman mediated apoptosis involves cross-talk between extrinsic/intrinsic pathways and oxidative regulation. AB - AIMS: Centchroman (CC) has been established as a potent antineoplastic agent in MCF-7 (ER+ve) and MDA MB-231 (ER-ve) Human Breast Cancer Cells (HBCCs) previously by us. To elucidate its antineoplastic action, we investigated the factors involved in cell-cycle progression and apoptosis. MAIN METHODS: Tamoxifen (TAM), a widely used antiestrogen was employed as a positive control. Role of Cycloheximide (CHX), Actinomycin-D (Act-D) and caspases were explored using specific inhibitors. Involvement of cell-cycle and apoptosis related factors were explored using western blotting and immunoprecipitation. KEY FINDINGS: Metabolic inhibitors viz. CHX, Act-D and pan-Caspase inhibitor, Z-VAD-FMK attenuated CC induced apoptosis. The upregulation of both p21(Waf1/Cip1) and p27(Kip1) along with p21-CDK6 (Cyclin Dependent Kinase 6) and p21-PCNA (Proliferating Cell Nuclear Antigen) interaction suggests their role in CC-induced cell-cycle arrest. The downregulation of Cyclin-D(1) and -E levels further confirms the antiestrogenic profile of CC. Unlike MDA MB-231, in MCF-7 cells, CC upregulates the level of phospho-p53 (Ser-15) and FasL, suggesting the involvement of extrinsic pathway. CC altered the intracytosolic balance of members of Bcl-2 family along with the cleavage of Poly (ADP-ribose) polymerase (PARP), Bcl-X(L), Bid and AIF (Apoptosis Inducing Factor). The evaluation of Mitogen Activated Protein Kinases (MAPKs) using specific inhibitors and Western blotting confirms CC-induced the upregulation of phospho-c-Jun and phospho-p38. Additionally elevated SOD (Superoxide Dismutase) and unaltered CAT (Catalase) expression further suggest the involvement of oxidative stress. SIGNIFICANCE: These results confirm that the antineoplasticity of CC in MCF-7 and MDA MB-231 cells involves the extrinsic and intrinsic pathways of apoptosis along with oxidative stress. PMID- 21034747 TI - A new approach regarding the treatment of preeclampsia and preterm labor. AB - Both preeclampsia and preterm delivery are important complications in pregnancy and are leading causes for maternal and perinatal morbidity and mortality. The underlying molecular mechanisms of both diseases remain unknown, thus treatments (beta2-stimulants and magnesium sulfate) are essentially symptomatic. Both molecules have molecular weights less than 5-8 kDa and cross the placental barrier thus exerting their effects on the fetus. In addition, the fetus produces peptide hormones that are highly vasoactive and uterotonic and increase in response to maternal stress and with continued development. Fetal peptides are also small molecules that inevitably leak across into the maternal circulation. Aminopeptidases such as placental leucine aminopeptidase (P-LAP) and aminopeptidase A (APA) are large molecules that do not cross the placental barrier. We have shown that APA acts as an antihypertensive agent in the pregnant spontaneously hypertensive rat by degrading vasoactive peptides and as a result returns the animal to a normotensive state. We have also noted that P-LAP acts as an anti-uterotonic agent by degrading uterotonic peptides, and as a result prolongs gestation in the pregnant mouse. Thus, P-LAP and APA represent promising agents for the treatment of preeclampsia and preterm labor by degrading bioactive hormones derived from the feto-placental circulation. PMID- 21034748 TI - Calcium- and phosphatidylinositol 3-kinase/Akt-dependent activation of endothelial nitric oxide synthase by apigenin. AB - AIMS: The generation of NO by endothelial nitric oxide synthase (eNOS) plays a major role in maintaining cardiovascular homeostasis. The objective of our present study was to investigate the effects of the flavone compound, apigenin, on eNOS activity and elucidate the molecular mechanisms underlying these effects in endothelial cells (ECs). MAIN METHODS: Bovine artery endothelial cells (BAECs) were exposed in a serum-free medium to apigenin. Cell viability was measured using an Alamar blue assay. The production of intracellular NO was determined using DAF-2/DA. The level of protein was examined by Western blotting. The intracellular Ca(2+) was measured using a fluorescent dye, Fura 2-AM. KEY FINDINGS: Apigenin significantly induced NO production after 6h of treatment. This production was inhibited by pretreatment with the eNOS inhibitor, N(omega) nitro l-arginine methyl ester (L-NAME). However, treatment with apigenin did not alter the eNOS protein levels but induced a sustained activation of eNOS Ser(1179) phosphorylation. Apigenin was further found to activate ERK1/2, JNK and Akt over various time courses in ECs. Treatment with specific PI3-kinase inhibitors significantly inhibited the increases in NO production and phosphorylation. In contrast, the inhibition of (ERK)1/2, JNK and p38 had no influence on NO production. In addition, apigenin stimulates an increase in the cytosolic Ca(2+) concentration. Apigenin-induced eNOS Ser(1179) phosphorylation and NO production are calcium-dependent, as pretreatment with extracellular or intracellular Ca(2+) chelators inhibits these processes. SIGNIFICANCE: Apigenin induced calcium-dependent activation of eNOS is primarily mediated via phosphatidylinositol 3-kinase- and Akt pathways, and occurs independently of the eNOS protein content. PMID- 21034749 TI - Inhibition of p300-HAT results in a reduced histone acetylation and down regulation of gene expression in cardiac myocytes. AB - AIMS: Histone acetylation plays an important role in cardiogenesis, but the underlying mechanism is unclear. In this study, we investigated the relationship between histone hypo-acetylation and the expression of cardiac-specific genes to explore the underlying mechanisms. MAIN METHODS: Cardiac-specific genes that physically interacted with p300 protein in mouse hearts were analyzed using chromatin immunoprecipitation (ChIP) assays. The cultured mouse neonatal cardiac myocytes were treated with curcumin with different concentrations and durations. The changes of histone acetyltransferase (HAT) activities, histone acetylation, cardiac-specific genes expression, and structure of chromatin were assessed by ELISA, Western blotting, quantitative RT-PCR, and ChIP assays, respectively. KEY FINDINGS: Results from the ChIP assay showed that GATA4, Nkx2.5, and Mef2c physically interacted with p300 protein. After treatment with 30 MUM curcumin for 24h, the HAT activities of cardiac myocytes were inhibited significantly. And the acetylation of whole histone H3 was reduced by 0.3983-fold compared to control groups (P<0.05). Accordingly, the expression of cardiac-specific genes, GATA4, Nkx2.5, and Mef2c, were significantly down-regulated. Acetylation of histone H3 bound with promoter regions of these genes was significantly reduced. SIGNIFICANCE: p300 interacts with cardiac-specific genes, GATA4, Nkx2.5 and Mef2c, and inhibition of p300-HAT by curcumin down-regulates their expression through the inhibition of histone H3 acetylation in the promoter regions. This finding indicates that p300-HAT mediated histone H3 acetylation plays an important role in the regulation of cardiac gene expression, which is a novel mechanism of epigenetic regulation in the heart during the development and in case of some congenital heart diseases. PMID- 21034751 TI - Sex-specific effects of early neonatal progesterone treatment on dopamine and serotonin metabolism in rat striatum and frontal cortex. AB - AIMS: The early neonatal period is critical for the development of the rodent brain. Neurosteroid levels in the brain decline from the late gestation to the neonatal period. Previous studies indicate effects of neurosteroid treatment during the neonatal period on the development of the dopaminergic system. In this study, we investigated the sex-specific effects of neonatal treatment with the neurosteroid progesterone on monoamine metabolism. Separately, we examined the contribution of pre-pubertal castration on the effect of neonatal treatment of pregnenolone (a neurosteroid precursor). MAIN METHODS: Progesterone (Experiment 1) or pregnenolone (Experiment 2) treatments in Sprague-Dawley rats were performed from postnatal days 3 through 7. Castration in experiment 2 was performed in male rats at postnatal day 21. We measured the brain tissue contents of dopamine, serotonin (5-HT), and their metabolites in rats at age 10 weeks. KEY FINDINGS: Results showed that neonatal progesterone treatment altered striatal 5 hydroxy-3-indolacetic acid/5-HT ratios in males and females in opposite directions, in addition to dopaminergic effects. The treatment also influenced dopamine and 5-HT metabolism without sex-specificity in the frontal cortex. In addition, there was no significant difference in striatal monoamine metabolism between sham-operated, castrated and castrated pregnenolone-treated group. SIGNIFICANCE: The present result indicates a sex-specific influence of progesterone during the early neonatal period on the development of the serotonergic system, depending on brain region in addition to of the dopaminergic system. PMID- 21034750 TI - U50,488H postconditioning reduces apoptosis after myocardial ischemia and reperfusion. AB - AIMS: Evidence has indicated U50,488H, a selective kappa-opioid receptor (kappa OR) agonist, administered before ischemia attenuates apoptosis and infarction during ischemia and reperfusion (I/R). However, it remains unclear whether U50,488H postconditioning reduces apoptosis during I/R. This study was designed, therefore, to test the hypothesis that U50,488H administered at the onset of reperfusion inhibits cardiomyocyte apoptosis and to investigate the underlying mechanisms. MAIN METHODS: Male Sprague-Dawley rats were subjected to myocardial ischemia and reperfusion(MI/R) and were randomized to receive either vehicle, U50,488H, U50,488H plus Nor-BNI, a selective kappa-OR antagonist, U50,488H plus wortmannin, a specific inhibitor of phosphoinositide 3'-kinase (PI3K), or U50,488H plus L-NAME, a nitric oxide synthase inhibitor (NOS inhibitor), immediately prior to reperfusion. In vitro study was performed on cultured neonatal cardiomyocytes subjected to simulated ischemia/reperfusion. KEY FINDINGS: Treatment with U50,488H resulted in increases in Akt and endothelial nitric oxide synthase (eNOS) phosphorylation with secondary NO production both in vivo and in vitro and these effect were completely blocked by wortmannin and specific Akt inhibitor(AI). L-NAME treatment had no effect on Akt and eNOS phosphorylation; but, significantly reduced NO production. Moreover, treatment with U50,488H markedly reduced myocardial apoptotic death. Treatment with wortmannin and specific Akt inhibitor abolished the anti-apoptotic effect of U50,488H. L-NAME also significantly attenuated the anti-apoptotic effect of U50,488H. SIGNIFICANCE: These results demonstrate that U50,488H administered immediately prior to reperfusion increases Akt phosphorylation through a PI3 kinase-dependent mechanism and reduces postischemic myocardial apoptosis. Phosphorylation of eNOS with secondary NO production contribute significantly to the anti-apoptotic effect of U50,488H postconditioning. PMID- 21034752 TI - Harmine, a natural beta-carboline alkaloid, upregulates astroglial glutamate transporter expression. AB - Glutamate is the predominant excitatory amino acid neurotransmitter in the mammalian central nervous system (CNS). Glutamate transporter EAAT2/GLT-1 is the physiologically dominant astroglial protein that inactivates synaptic glutamate. Previous studies have shown that EAAT2 dysfunction leads to excessive extracellular glutamate and may contribute to various neurological disorders including amyotrophic lateral sclerosis (ALS). The recent discovery of the neuroprotective properties of ceftriaxone, a beta lactam antibiotic, suggested that increasing EAAT2/GLT-1 gene expression might be beneficial in ALS and other neurological/psychiatric disorders by augmenting astrocytic glutamate uptake. Here we report our efforts to develop a new screening assay for identifying compounds that activate EAAT2 gene expression. We generated fetal derived-human immortalized astroglial cells that are stably expressing a firefly luciferase reporter under the control of the human EAAT2 promoter. When screening a library of 1040 FDA approved compounds and natural products, we identified harmine, a naturally occurring beta-carboline alkaloid, as one of the top hits for activating the EAAT2 promoter. We further tested harmine in our in vitro cell culture systems and confirmed its ability to increase EAAT2/GLT1 gene expression and functional glutamate uptake activity. We next tested its efficacy in both wild type animals and in an ALS animal model of disease and demonstrated that harmine effectively increased GLT-1 protein and glutamate transporter activity in vivo. Our studies provide potential novel neurotherapeutics by modulating the activity of glutamate transporters via gene activation. This article is part of a Special Issue entitled 'Trends in neuropharmacology: in memory of Erminio Costa'. PMID- 21034753 TI - Apotransferrin protects cortical neurons from hemoglobin toxicity. AB - The protective effect of iron chelators in experimental models of intracerebral hemorrhage suggests that nonheme iron may contribute to injury to perihematomal cells. Therapy with high affinity iron chelators is limited by their toxicity, which may be due in part to sequestration of metals in an inaccessible complex. Transferrin is unique in chelating iron with very high affinity while delivering it to cells as needed via receptor-mediated endocytosis. However, its efficacy against iron-mediated neuronal injury has never been described, and was therefore evaluated in this study using an established cell culture model of hemoglobin neurotoxicity. At concentrations similar to that of CSF transferrin (50-100 micrograms/ml), both iron-saturated holotransferrin and apotransferrin were nontoxic per se. Overnight exposure to 3 MUM purified human hemoglobin in serum free culture medium resulted in death, as measured by lactate dehydrogenase release assay, of about three-quarters of neurons. Significant increases in culture iron, malondialdehyde, protein carbonyls, ferritin and heme oxygenase-1 were also observed. Holotransferrin had no effect on these parameters, but all were attenuated by 50-100 micrograms/ml apotransferrin. The effect of apotransferrin was very similar to that of deferoxamine at a concentration that provided equivalent iron binding capacity, and was not antagonized by concomitant treatment with holotransferrin. Transferrin receptor-1 expression was localized to neurons and was not altered by hemoglobin or transferrin treatment. These results suggest that apotransferrin may mitigate the neurotoxicity of hemoglobin after intracerebral hemorrhage. Increasing its concentration in perihematomal tissue may be beneficial. PMID- 21034754 TI - Dopamine susceptibility of APO-SUS rats is not per se coupled to HPA-axis activity. AB - A synergistic relationship is thought to exist between hypothalamic-pituitary adrenal (HPA) axis activity and dopamine neurotransmission. To test whether a high response to dopamine indeed implies a hyperactive HPA-axis, we here used Wistar rats that were selected twice independently (original and replicate lines) for a high or low susceptibility to the dopamine receptor agonist apomorphine (so called APO-SUS and APO-UNSUS rats, respectively). The APO-SUS rats from the original line displayed a hyperactive HPA-axis in that higher basal and stress induced adrenocorticotropic hormone (ACTH) levels, and lower basal free corticosterone levels were observed than those found in the original APO-UNSUS rats. In contrast, the activity of the HPA-axis in the APO-SUS rats from the replicate line did not differ from that in the replicate APO-UNSUS rats. Thus, in the APO-SUS/APO-UNSUS rat model the level of HPA-axis activity is not necessarily causally linked to dopamine responsiveness, implying that a hyperactive HPA-axis is not a prerequisite for a high dopaminergic response. PMID- 21034755 TI - 20-Hydroxyecdysone regulation of H-fibroin gene in the stored grain pest Corcyra cephalonica, during the last instar larval development. AB - 20-Hydroxyecdysone (20E) controls molting, metamorphosis and reproduction of insects. It binds to a heterodimeric complex of ecdysone receptor (EcR) and ultraspiracle (USP), and regulates the transcription of genes containing ecdysone response elements (EcREs). However, the 20E regulation of silk fibroin genes is largely unexplored. In most lepidopteran larvae, the silk fibroin primarily consists of a large protein, heavy chain fibroin (H-fibroin) that is associated with two small proteins, L-chain fibroin and P25. In the present study, we demonstrate that 20E regulates the expression of H-fibroin gene in Corcyra cephalonica, in a dose-dependent manner during the last instar larval development. Semi-quantitative and real-time PCR studies reveal that physiological doses of 20E do not alter the normal expression, whereas higher doses cause a significant decline in the expression. Luciferase activity assays and gel shift experiments further confirm the presence of a functional EcRE in the upstream region of H-fibroin which regulates the ecdysteroid dependent transcriptional activity of fibroin gene through EcR. In vitro treatment with 20E mimicking insecticides, RH-5849 and RH-5992 decreases the expression of H-fibroin in isolated salivary glands. Insects fed with similar concentrations of these insecticides, metamorphose abnormally. Differences are also observed in the ultrastructure of the silk fibers of control and insecticide fed insects providing additional insight into the disruptive effects of these non-steroidal ecdysteroid agonists. PMID- 21034756 TI - Common plant toxicology: a comparison of national and southwest Ohio data trends on plant poisonings in the 21st century. AB - Data from the American Association of Poison Control Centers (AAPCC) and the Cincinnati-based Drug and Poison Information Center (DPIC) were analyzed to determine the incidence and trends of human plant poisonings since the year 2000. Approximately 3.4% of the approximately 4.3 million annual calls to the AAPCC centers involved plants, with a higher fraction (4.5%) for pediatric exposures. Nearly 70% of plant exposures occurred in children under six. Only 8% of cases required treatment in a health-care facility, and only 0.1% (in 2008) were considered severe outcomes. The most prominent groups of plants involved in exposures are those containing oxalates, and the most common symptom is gastroenteritis. The top 12 identified plants (in descending order) nationally were Spathiphyllum species (peace lilly), Philodendron species (philodendron), Euphorbia pulcherrima (poinssettia), Ilex species (holly), Phytolacca americana (pokeweed), Toxicodendron radicans (poison ivy), Capsicum (pepper), Ficus (rubber tree, weeping fig), Crassula argentea (jade plant), Diffenbachia (dumb cane), Epipremnum areum (pothos) and Schlumbergera bridesii (Christmas cactus). Broad overlaps between the DPIC and the AAPCC incidence data were noted, with essentially the same plant species in each dataset. The nature of the various toxins, the symptomatology and potential treatments are discussed for the highest ranking plant species. PMID- 21034757 TI - Assessing the toxic effects of ethylene glycol ethers using Quantitative Structure Toxicity Relationship models. AB - Experimental determination of toxicity profiles consumes a great deal of time, money, and other resources. Consequently, businesses, societies, and regulators strive for reliable alternatives such as Quantitative Structure Toxicity Relationship (QSTR) models to fill gaps in toxicity profiles of compounds of concern to human health. The use of glycol ethers and their health effects have recently attracted the attention of international organizations such as the World Health Organization (WHO). The board members of Concise International Chemical Assessment Documents (CICAD) recently identified inadequate testing as well as gaps in toxicity profiles of ethylene glycol mono-n-alkyl ethers (EGEs). The CICAD board requested the ATSDR Computational Toxicology and Methods Development Laboratory to conduct QSTR assessments of certain specific toxicity endpoints for these chemicals. In order to evaluate the potential health effects of EGEs, CICAD proposed a critical QSTR analysis of the mutagenicity, carcinogenicity, and developmental effects of EGEs and other selected chemicals. We report here results of the application of QSTRs to assess rodent carcinogenicity, mutagenicity, and developmental toxicity of four EGEs: 2-methoxyethanol, 2 ethoxyethanol, 2-propoxyethanol, and 2-butoxyethanol and their metabolites. Neither mutagenicity nor carcinogenicity is indicated for the parent compounds, but these compounds are predicted to be developmental toxicants. The predicted toxicity effects were subjected to reverse QSTR (rQSTR) analysis to identify structural attributes that may be the main drivers of the developmental toxicity potential of these compounds. PMID- 21034758 TI - Introduction to benchmark dose methods and U.S. EPA's benchmark dose software (BMDS) version 2.1.1. AB - Traditionally, the No-Observed-Adverse-Effect-Level (NOAEL) approach has been used to determine the point of departure (POD) from animal toxicology data for use in human health risk assessments. However, this approach is subject to substantial limitations that have been well defined, such as strict dependence on the dose selection, dose spacing, and sample size of the study from which the critical effect has been identified. Also, the NOAEL approach fails to take into consideration the shape of the dose-response curve and other related information. The benchmark dose (BMD) method, originally proposed as an alternative to the NOAEL methodology in the 1980s, addresses many of the limitations of the NOAEL method. It is less dependent on dose selection and spacing, and it takes into account the shape of the dose-response curve. In addition, the estimation of a BMD 95% lower bound confidence limit (BMDL) results in a POD that appropriately accounts for study quality (i.e., sample size). With the recent advent of user friendly BMD software programs, including the U.S. Environmental Protection Agency's (U.S. EPA) Benchmark Dose Software (BMDS), BMD has become the method of choice for many health organizations world-wide. This paper discusses the BMD methods and corresponding software (i.e., BMDS version 2.1.1) that have been developed by the U.S. EPA, and includes a comparison with recently released European Food Safety Authority (EFSA) BMD guidance. PMID- 21034759 TI - A hybrid approach to advancing quantitative prediction of tissue distribution of basic drugs in human. AB - A general toxicity of basic drugs is related to phospholipidosis in tissues. Therefore, it is essential to predict the tissue distribution of basic drugs to facilitate an initial estimate of that toxicity. The objective of the present study was to further assess the original prediction method that consisted of using the binding to red blood cells measured in vitro for the unbound drug (RBCu) as a surrogate for tissue distribution, by correlating it to unbound tissue:plasma partition coefficients (Kpu) of several tissues, and finally to predict volume of distribution at steady-state (V(ss)) in humans under in vivo conditions. This correlation method demonstrated inaccurate predictions of V(ss) for particular basic drugs that did not follow the original correlation principle. Therefore, the novelty of this study is to provide clarity on the actual hypotheses to identify i) the impact of pharmacological mode of action on the generic correlation of RBCu-Kpu, ii) additional mechanisms of tissue distribution for the outlier drugs, iii) molecular features and properties that differentiate compounds as outliers in the original correlation analysis in order to facilitate its applicability domain alongside the properties already used so far, and finally iv) to present a novel and refined correlation method that is superior to what has been previously published for the prediction of human V(ss) of basic drugs. Applying a refined correlation method after identifying outliers would facilitate the prediction of more accurate distribution parameters as key inputs used in physiologically based pharmacokinetic (PBPK) and phospholipidosis models. PMID- 21034760 TI - Advances in exposure and toxicity assessment of particulate matter: an overview of presentations at the 2009 Toxicology and Risk Assessment Conference. AB - The 2009 Toxicology and Risk Assessment Conference (TRAC) session on "Advances in Exposure and Toxicity Assessment of Particulate Matter" was held in April 2009 in West Chester, OH. The goal of this session was to bring together toxicology, geology and risk assessment experts from the Department of Defense and academia to examine issues in exposure assessment and report on recent epidemiological findings of health effects associated with particulate matter (PM) exposure. Important aspects of PM exposure research are to detect and monitor low levels of PM with various chemical compositions and to assess the health risks associated with these exposures. As part of the overall theme, some presenters discussed collection methods for sand and dust from Iraqi and Afghanistan regions, health issues among deployed personnel, and future directions for risk assessment research among these populations. The remaining speakers focused on the toxicity of ultrafine PM and the characterization of aerosols generated during ballistic impacts of tungsten heavy alloys. PMID- 21034761 TI - When the facts are just not enough: credibly communicating about risk is riskier when emotions run high and time is short. AB - When discussing risk with people, commonly subject matter experts believe that conveying the facts will be enough to allow people to assess a risk and respond rationally to that risk. Because of this expectation, experts often become exasperated by the seemingly illogical way people assess personal risk and choose to manage that risk. In crisis situations when the risk information is less defined and choices must be made within impossible time constraints, the thought processes may be even more susceptible to faulty heuristics. Understanding the perception of risk is essential to understanding why the public becomes more or less upset by events. This article explores the psychological underpinnings of risk assessment within emotionally laden events and the risk communication practices that may facilitate subject matter experts to provide the facts in a manner so they can be more certain those facts are being heard. Source credibility is foundational to risk communication practices. The public meeting is one example in which these best practices can be exercised. Risks are risky because risk perceptions differ and the psychosocial environment in which risk is discussed complicates making risk decisions. Experts who want to influence the actions of the public related to a threat or risk should understand that decisions often involve emotional as well as logical components. The media and other social entities will also influence the risk context. The Center for Disease Control and Prevention's crisis and emergency-risk communication (CERC) principles are intended to increase credibility and recognize emotional components of an event. During a risk event, CERC works to calm emotions and increase trust which can help people apply the expertise being offered by response officials. PMID- 21034762 TI - Emerging contaminants: presentations at the 2009 Toxicology and Risk Assessment Conference. AB - A session entitled "Emerging Contaminants" was held in April 2009 in Cincinnati, OH at the 2009 Toxicology and Risk Assessment Conference. The purpose of the session was to share information on both programmatic and technical aspects associated with emerging contaminants. Emerging contaminants are chemicals or materials that are characterized by a perceived or real threat to human health or environment, a lack of published health standards or an evolving standard. A contaminant may also be "emerging" because of the discovery of a new source, a new pathway to humans, or a new detection method or technology. The session included five speakers representing the Department of Defense (DoD), the Environmental Protection Agency (EPA), and each of the military services. The DoD created the Emerging Contaminant Directorate to proactively address environmental, health, and safety concerns associated with emerging contaminants. This session described the scan-watch-action list process, impact assessment methodology, and integrated risk management concept that DoD has implemented to manage emerging contaminants. EPA presented emerging trends in health risk assessment. Researchers made technical presentations on the status of some emerging contaminates in the assessment process (i.e. manganese, RDX, and naphthalene). PMID- 21034763 TI - Bioavailability of soy isoflavones through placental/lactational transfer and soy food. AB - Isoflavones are non-nutritive components of soy responsible for estrogenic responses observed in vitro and in experimental animals. Possible beneficial effects (e.g., reduction of serum lipids, increased bone mineral density, relief of hot flashes and other menopausal symptoms, mammary and prostate cancer chemoprevention) in humans have been attributed to consumption of isoflavones but evidence for potential adverse effects (e.g., stimulation of estrogen-dependent mammary tumors and aberrant perinatal development) has also been reported in experimental animal models. Bioavailability from appropriate food matrices and exposure during different life stages are both critical determinants of isoflavone effects. For these reasons, it is important to compare isoflavone bioavailability in adults to that in fetal and neonatal animals for a more complete understanding of potential susceptibility issues. Studies of the major soy isoflavone genistein were conducted in pregnant and lactating Sprague-Dawley rats to quantify placental and lactational transfer to plasma and brain to understand better biological effects observed in multigenerational studies. In addition, studies were conducted with genistein in adult Balb/c mice to define absolute bioavailability from both gavage and soy protein isolate (SPI) containing food. The information derived from these studies makes it possible to predict internal exposures of children to genistein from soy infant formula, which is manufactured using SPI. PMID- 21034765 TI - A model for considering different discourse communities within the toxicological and environmental sciences: an approach for addressing jargon and personally subjective vocabulary. AB - Discourse speak is a powerful communication shorthand between individuals in the same discourse group. Discourse speak consists of both jargon, the unique--but understood--terminology used in the discourse group, and a member's own personally subjective vocabulary, wording that is commonly used in the discourse group but has no true consensus-based meaning. It is my observation that sometimes when scientists write, they generally focus solely on content (the pedant's stance), and, consequently, can fail to consciously consider audience, and, by extension, they fail to anticipate that their publication may reach beyond their own discourse group. If scientists do not consciously consider their intended audience and do not adapt their language for "outsiders" who might be part of the audience, the usefulness of the publication becomes limited because the intended meaning can be lost. Thus, as explained in the subsequent commentary, effective communication in the sciences not only involves defendable science but, also, a conscious perception of audience through a deliberate recognition of one's own discourse speak. PMID- 21034764 TI - Exposure to Pb, Cd, and As mixtures potentiates the production of oxidative stress precursors: 30-day, 90-day, and 180-day drinking water studies in rats. AB - Exposure to chemical mixtures is a common and important determinant of toxicity and is of particular concern due to their appearance in sources of drinking water. Despite this, few in vivo mixture studies have been conducted to date to understand the health impact of chemical mixtures compared to single chemicals. Interactive effects of lead (Pb), cadmium (Cd) and arsenic (As) were evaluated in 30-, 90-, and 180-day factorial design drinking water studies in rats designed to test the hypothesis that ingestion of such mixtures at individual component Lowest-Observed-Effect-Levels (LOELs) results in increased levels of the pro oxidant delta aminolevulinic acid (ALA), iron, and copper. LOEL levels of Pb, Cd, and As mixtures resulted in the increased presence of mediators of oxidative stress such as ALA, copper, and iron. ALA increases were followed by statistically significant increases in kidney copper in the 90- and 180-day studies. Statistical evidence of interaction was identified for six biologically relevant variables: blood delta aminolevulinic acid dehydratase (ALAD), kidney ALAD, urinary ALA, urinary iron, kidney iron, and kidney copper. The current investigations underscore the importance of considering interactive effects that common toxic agents such as Pb, Cd, and As may have upon one another at low-dose levels. The interactions between known toxic trace elements at biologically relevant concentrations shown here demonstrate a clear need to rigorously review methods by which national/international agencies assess health risks of chemicals, since exposures may commonly occur as complex mixtures. PMID- 21034766 TI - SAR/QSAR methods in public health practice. AB - Methods of (Quantitative) Structure-Activity Relationship ((Q)SAR) modeling play an important and active role in ATSDR programs in support of the Agency mission to protect human populations from exposure to environmental contaminants. They are used for cross-chemical extrapolation to complement the traditional toxicological approach when chemical-specific information is unavailable. SAR and QSAR methods are used to investigate adverse health effects and exposure levels, bioavailability, and pharmacokinetic properties of hazardous chemical compounds. They are applied as a part of an integrated systematic approach in the development of Health Guidance Values (HGVs), such as ATSDR Minimal Risk Levels, which are used to protect populations exposed to toxic chemicals at hazardous waste sites. (Q)SAR analyses are incorporated into ATSDR documents (such as the toxicological profiles and chemical-specific health consultations) to support environmental health assessments, prioritization of environmental chemical hazards, and to improve study design, when filling the priority data needs (PDNs) as mandated by Congress, in instances when experimental information is insufficient. These cases are illustrated by several examples, which explain how ATSDR applies (Q)SAR methods in public health practice. PMID- 21034767 TI - Approaches to cancer assessment in EPA's Integrated Risk Information System. AB - The U.S. Environmental Protection Agency's (EPA) Integrated Risk Information System (IRIS) Program develops assessments of health effects that may result from chronic exposure to chemicals in the environment. The IRIS database contains more than 540 assessments. When supported by available data, IRIS assessments provide quantitative analyses of carcinogenic effects. Since publication of EPA's 2005 Guidelines for Carcinogen Risk Assessment, IRIS cancer assessments have implemented new approaches recommended in these guidelines and expanded the use of complex scientific methods to perform quantitative dose-response assessments. Two case studies of the application of the mode of action framework from the 2005 Cancer Guidelines are presented in this paper. The first is a case study of 1,2,3 trichloropropane, as an example of a chemical with a mutagenic mode of carcinogenic action thus warranting the application of age-dependent adjustment factors for early-life exposure; the second is a case study of ethylene glycol monobutyl ether, as an example of a chemical with a carcinogenic action consistent with a nonlinear extrapolation approach. The use of physiologically based pharmacokinetic (PBPK) modeling to quantify interindividual variability and account for human parameter uncertainty as part of a quantitative cancer assessment is illustrated using a case study involving probabilistic PBPK modeling for dichloromethane. We also discuss statistical issues in assessing trends and model fit for tumor dose-response data, analysis of the combined risk from multiple types of tumors, and application of life-table methods for using human data to derive cancer risk estimates. These issues reflect the complexity and challenges faced in assessing the carcinogenic risks from exposure to environmental chemicals, and provide a view of the current trends in IRIS carcinogenicity risk assessment. PMID- 21034768 TI - A new look at gamma? High- (>60 Hz) gamma-band activity in cortical networks: function, mechanisms and impairment. AB - gamma-band oscillations are thought to play a crucial role in information processing in cortical networks. In addition to oscillatory activity between 30 and 60 Hz, current evidence from electro- and magnetoencephalography (EEG/MEG) and local-field potentials (LFPs) has consistently shown oscillations >60 Hz (high gamma-band) whose function and generating mechanisms are unclear. In the present paper, we summarize data that highlights the importance of high gamma band activity for cortical computations through establishing correlations between the modulation of oscillations in the 60-200 Hz frequency and specific cognitive functions. Moreover, we will suggest that high gamma-band activity is impaired in neuropsychiatric disorders, such as schizophrenia and epilepsy. In the final part of the paper, we will review physiological mechanisms underlying the generation of high gamma-band oscillations and discuss the functional implications of low vs. high gamma-band activity patterns in cortical networks. PMID- 21034769 TI - Individual sequence variability and functional activities of fibrinogen-related proteins (FREPs) in the Mediterranean mussel (Mytilus galloprovincialis) suggest ancient and complex immune recognition models in invertebrates. AB - In this paper, we describe sequences of fibrinogen-related proteins (FREPs) in the Mediterranean mussel Mytilus galloprovincialis (MuFREPs) with the fibrinogen domain probably involved in the antigen recognition, but without the additional collagen-like domain of ficolins, molecules responsible for complement activation by the lectin pathway. Although they do not seem to be true or primive ficolins since the phylogenetic analysis are not conclusive enough, their expression is increased after bacterial infection or PAMPs treatment and they present opsonic activities similar to mammalian ficolins. The most remarkable aspect of these sequences was the existence of a very diverse set of FREP sequences among and within individuals (different mussels do not share any identical sequence) which parallels the extraordinary complexity of the immune system, suggesting the existence of a primitive system with a potential capacity to recognize and eliminate different kind of pathogens. PMID- 21034770 TI - Molecular cloning of the porcine RANTES promoter: functional characterization of dsDNA/dsRNA response elements in PK-15 cells. AB - The chemokine RANTES plays an essential role in inflammation and immune response. In this study, we cloned the nucleotide sequence of the 5'-flanking region of the porcine RANTES (poRANTES) gene and characterized the regulatory elements that activate transcription. Analyses of a series of 5' deletion constructs demonstrated that a 266 bp region (-220/+46) that spanned the potential transcription start site of the poRANTES gene was sufficient to activate transcription in PK-15 cells. Furthermore, our results indicated that dsDNA/dsRNA significantly induced poRANTES promoter activity and expression of mRNA levels in a time- and dose-dependent manner. Promoter deletions and mutagenesis experiments indicated that an interferon-stimulated responsive element (ISRE) was critical for dsDNA/dsRNA-induced poRANTES transcription. In addition, porcine interferon regulatory factor 3 (IRF-3) and IRF-7 play important roles in dsDNA/dsRNA-induced poRANTES expression. PMID- 21034771 TI - Serologic assessment of the risk of developing chronic Q fever in cohorts of acutely infected individuals. AB - OBJECTIVE: The aim of this study was to assess the clinical significance of serological profiles suggestive of chronic Q fever after acute infection. METHODS: A prospective follow-up study consisting of two separate cohorts was conducted to monitor the serological evolution of Q fever. The first cohort comprised subjects with acute Q fever diagnosed in 2004-2007 and the second enrolled subjects whose infection occurred in 2009. The indirect immunofluorescence assay was used for serological monitoring, with serum PCR testing added for subjects whose serological profiles revealed high titers of anti-phase I IgG>=800, titers suggestive of chronic Q fever. RESULTS: In the first cohort of 92 persons, seventeen (18%) subjects had serological profiles suggestive of chronic Q fever (titers of anti-phase I IgG: 1280-5120, median: 1280) after a median follow-up period of 606.5 days. After a further follow-up (median period: 592 days) exclusively for those seventeen subjects, serological resolution with fourfold decrease of titers of anti-phase I IgG was noted in five of them. In the second cohort, only one (4%) of the twenty-eight subjects had high levels of anti-phase I IgG 180 days after acute infection. All the eighteen subjects with high levels of anti-phase I IgG were asymptomatic and had negative serum PCR testing. The different prevalence of subjects with high titers of anti phase I IgG in the two cohorts was associated with duration of follow-up period (P < .01). CONCLUSIONS: Subjects with high titers of anti-phase I IgG>=800 was not uncommon and might not be detected until more than six months after acute Q fever infection. Asymptomatic subjects with high levels of anti-phase I IgG alone should not be treated as chronic Q fever and might not need continued serological monitoring in the absence of predisposing factors to chronic Q fever. PMID- 21034772 TI - Multiplex RT-PCR for rapid detection and differentiation of class I and class II Newcastle disease viruses. AB - A multiplex RT-PCR was developed for detection and differentiation of class I and class II strains of Newcastle disease virus (NDV). The method was shown to have high specificity and sensitivity. The results obtained from the multiplex RT-PCR for a total of 67 NDV field isolates obtained in 2009 were consistent with those obtained by nucleotide sequencing and phylogenetic analysis. A phylogenetic tree based on the partial sequences of the F gene revealed that the 67 field isolates of NDV could be divided into two classes. Twenty-seven NDV isolates were grouped into class I, and two genotypes were identified. Most of the class I isolates were determined to be of genotype 3, with the exception of isolate NDV09-034, which belonged to genotype 2. Forty class II NDV isolates were divided into three genotypes, namely genotype VII (27 isolates), genotype I (2 isolates) and genotype II (11 isolates). Isolates of genotypes I and II in class II were shown to be related to commercial vaccine strains used commonly in China. All isolates of genotype VII were predicted to be virulent, on the basis of the sequence motif at the cleavage site of the F gene. This genotype has become predominantly responsible for most outbreaks of ND in China in recent years. In conclusion, this multiplex RT-PCR provides a new assay for rapid detection and differentiation of both classes of NDV isolates. PMID- 21034773 TI - Comparison of commercial systems for extraction of nucleic acids from DNA/RNA respiratory pathogens. AB - This study compared six automated nucleic acid extraction systems and one manual kit for their ability to recover nucleic acids from human nasal wash specimens spiked with five respiratory pathogens, representing Gram-positive bacteria (Streptococcus pyogenes), Gram-negative bacteria (Legionella pneumophila), DNA viruses (adenovirus), segmented RNA viruses (human influenza virus A), and non segmented RNA viruses (respiratory syncytial virus). The robots and kit evaluated represent major commercially available methods that are capable of simultaneous extraction of DNA and RNA from respiratory specimens, and included platforms based on magnetic-bead technology (KingFisher mL, Biorobot EZ1, easyMAG, KingFisher Flex, and MagNA Pure Compact) or glass fiber filter technology (Biorobot MDX and the manual kit Allprep). All methods yielded extracts free of cross-contamination and RT-PCR inhibition. All automated systems recovered L. pneumophila and adenovirus DNA equivalently. However, the MagNA Pure protocol demonstrated more than 4-fold higher DNA recovery from the S. pyogenes than other methods. The KingFisher mL and easyMAG protocols provided 1- to 3-log wider linearity and extracted 3- to 4-fold more RNA from the human influenza virus and respiratory syncytial virus. These findings suggest that systems differed in nucleic acid recovery, reproducibility, and linearity in a pathogen specific manner. PMID- 21034774 TI - Detection of Tomato black ring virus by real-time one-step RT-PCR. AB - A TaqMan-based real-time one-step RT-PCR assay was developed for the rapid detection of Tomato black ring virus (TBRV), a significant plant pathogen which infects a wide range of economically important crops. Primers and a probe were designed against existing genomic sequences to amplify a 72 bp fragment from RNA 2. The assay amplified all isolates of TBRV tested, but no amplification was observed from the RNA of other nepovirus species or healthy host plants. The detection limit of the assay was estimated to be around nine copies of the TBRV target region in total RNA. A comparison with conventional RT-PCR and ELISA, indicated that ELISA, the current standard test method, lacked specificity and reacted to all nepovirus species tested, while conventional RT-PCR was approximately ten-fold less sensitive than the real-time RT-PCR assay. Finally, the real-time RT-PCR assay was tested using five different RT-PCR reagent kits and was found to be robust and reliable, with no significant differences in sensitivity being found. The development of this rapid assay should aid in quarantine and post-border surveys for regulatory agencies. PMID- 21034775 TI - Cross-genotypic polyclonal anti-HCV antibodies from human ascitic fluid. AB - Many anti-HCV antibodies are available, but more are needed for research and clinical applications. This study examines whether ascitic fluid from cirrhotic patients could be a source of reagent-grade antibodies. Ascitic fluid from 29 HCV patients was screened by ELISA for anti-HCV antibodies against three viral proteins: core, NS4B, and NS5A. Significant patient-to-patient variability in anti-HCV antibody titers was observed. Total ascitic fluid IgG purified by Protein-A chromatography reacted with HCV proteins in immunoblots, cell extracts, and replicon-expressing cells. Affinity-purification using synthetic peptides as bait allowed the preparation of cross-genotypic antibodies directed against pre selected regions of HCV core, NS4B, and NS5A proteins. The performance of the polyclonal antibodies was comparable to that of monoclonal antibodies. Anti-NS4B antibody preparations reacted with genotype 1a, 1b, and 2a NS4B proteins in immunoblots and allowed NS4B to be localized in replicon-expressing cells. Ascitic fluid is an abundant source of human polyclonal cross-genotypic antibodies that can be used as an alternative to blood. This study shows the utility of selectively purifying human polyclonal antibodies from ascitic fluid. Affinity purification allows antibodies to be selected that are comparable to monoclonal antibodies in their ability to react with targeted regions of viral proteins. PMID- 21034776 TI - A versatile vector for the production of pseudotyped viruses expressing gp120 antigens from different clades of primary HIV-1 isolates. AB - A novel HIV-1 Env expression vector (SF162-Z) was developed by introducing two new cloning sites on the backbone of an existing vector that produces a full length Env from HIV-1 SF162 isolate. These sites facilitate the swapping of the gp120 portion of the SF162 Env with matching gp120 antigens from HIV-1 isolates of different genetic clades. Final production of functional pseudotyped viruses will express chimeric Env antigens, including gp41 of the parental SF162 and gp120 from other primary isolates. This system is useful for testing the neutralizing sensitivity of partial env gene products frequently identified in viral quasi species in patients infected with HIV or when only partial gp120 gene products are available. PMID- 21034777 TI - Bromocriptine increased operant responding for high fat food but decreased chow intake in both obesity-prone and resistant rats. AB - Dopamine (DA) and DA D2 receptors (D2R) have been implicated in obesity and are thought to be involved in the rewarding properties of food. Osborne-Mendel (OM) rats are susceptible to diet induced obesity (DIO) while S5B/P (S5B) rats are resistant when given a high-fat diet. Here we hypothesized that the two strains would differ in high-fat food self-administration (FSA) and that the D2R agonist bromocriptine (BC) would differently affect their behavior. Ad-libitum fed OM and S5B/P rats were tested in a FSA operant chamber and were trained to lever press for high-fat food pellets under a fixed-ratio (FR1) and a progressive ratio (PR) schedule. After sixteen days of PR sessions, rats were treated with three different doses of BC (1, 10 and 20 mg/kg). No significant differences were found between the two strains in the number of active lever presses. BC treatment (10 mg/kg and 20 mg/kg) increased the number of active lever presses (10 mg/kg having the strongest effect) whereas it decreased rat chow intake in the home cage with equivalent effects in both strains. These effects were not observed on the day of BC administration but on the day following its administration. Our results suggest that these two strains have similar motivation for procuring high fat food using this paradigm. BC increased operant responding for high-fat pellets but decreased chow intake in both strains, suggesting that D2R stimulation may have enhanced the motivational drive to procure the fatty food while correspondingly decreasing the intake of regular food. These findings suggest that susceptibility to dietary obesity (prior to the onset of obesity) may not affect operant motivation for a palatable high fat food and that differential susceptibility to obesity may be related to differential sensitivity to D2R stimulation. PMID- 21034778 TI - Dysphagia in a patient with recurrent bilateral eyelid ptosis. PMID- 21034779 TI - Prolonging survival in patients with cirrhosis: old drugs with new indications. PMID- 21034780 TI - N-acetylglucosamine transferase is an integral component of a kinesin-directed mitochondrial trafficking complex. AB - Trafficking kinesin proteins (TRAKs) 1 and 2 are kinesin-associated proteins proposed to function in excitable tissues as adaptors in anterograde trafficking of cargoes including mitochondria. They are known to associate with N acetylglucosamine transferase and the mitochondrial rho GTPase, Miro. We used confocal imaging, Forster resonance energy transfer and immunoprecipitations to investigate association between TRAKs1/2, N-acetylglucosamine transferase, the prototypic kinesin-1, KIF5C, and Miro. We demonstrate that in COS-7 cells, N acetylglucosamine transferase, KIF5C and TRAKs1/2 co-distribute. Forster resonance energy transfer was observed between N-acetylglucosamine transferase and TRAKs1/2. Despite co-distributing with KIF5C and immunoprecipitations demonstrating a TRAK1/2, N-acetylglucosamine transferase and KIF5C ternary complex, no Forster resonance energy transfer was detected between N acetylglucosamine transferase and KIF5C. KIF5C, N-acetylglucosamine transferase, TRAKs1/2 and Miro formed a quaternary complex. The presence of N acteylglucosamine transferase partially prevented redistribution of mitochondria induced by trafficking proteins 1/2 and KIF5C. TRAK2 was a substrate for N acetylglucosamine transferase with TRAK2 (S562) identified as a site of O-N acetylglucosamine modification. These findings substantiate trafficking kinesin proteins as scaffolds for the formation of a multi-component complex involved in anterograde trafficking of mitochondria. They further suggest that O glycosylation may regulate complex formation. PMID- 21034782 TI - Coherent with laughter: subjective experience, behavior, and physiological responses during amusement and joy. AB - Emotion research historically has adopted a fairly homogeneous view of positive emotions. The aim of the current study was to explore how two positive emotions, amusement and joy, differ in subjective, behavioral, cardiovascular, and respiratory characteristics. Thirty-nine participants viewed two film clips, each selected to elicit amusement or joy. As predicted, participants reported more amusement, showed more positive facial expressions and laughter, and exhibited less heart rate deceleration and a larger increase in respiratory amplitude in response to the amusement clip than in response to the joy clip. In addition, subjective, behavioral, and physiological indicators were more closely related in amusement than joy, which was largely attributable to laughter during amusement. The current study adds to a growing literature suggesting the importance of adopting a more nuanced conceptualization of positive emotion. PMID- 21034781 TI - Isolation of previously uncultured rumen bacteria by dilution to extinction using a new liquid culture medium. AB - A new anaerobic medium that mimics the salts composition of rumen fluid was used in conjunction with a dilution method of liquid culture to isolate fermentative bacteria from the rumen of a grass-fed sheep. The aim was to inoculate a large number of culture tubes each with a mean of <1 culturable cell, which should maximize the number of cultures that develop from a single bacterium. This minimizes the effort that has to be put into purifying the resultant cultures. Of 1000 tubes, 139 were growth positive. Of the 93 that were able to be subcultured, 54 (58%) appeared to be pure cultures. The phylogenetic placements of these 54 cultures, together with another 6 cultures obtained from a preliminary study, were determined. Using a criterion of <93% 16S rRNA gene sequence identity to a previously named bacterium as a proxy for defining a new genus, 27 (45%) of the 60 cultures belonged to 14 potentially novel genera. Many of these had 16S rRNA genes that shared >97% sequence identity to genes of uncultured bacteria detected in various gastrointestinal environments. This strategy has therefore allowed us to cultivate many novel rumen bacteria, opening the way to overcoming the lack of cultures of many of the groups detected using cultivation-independent methods. PMID- 21034783 TI - Long-term effects of psychosocial factors of home and work on biomarkers of stress. AB - INTRODUCTION: The current study analyzed the relationship between psychosocial factors measured at baseline and heart rate variability (HRV) and salivary cortisol measured at baseline and again, six years later. METHODS: In 2002 and 2008, measurements of HRV and salivary cortisol at three time points were obtained from 70 healthy participants (48 women and 22 men). The associations between the psychosocial factors measured in 2002 and the dependent variables, HRV and salivary cortisol measured in 2002 and 2008, were examined using a series of repeated measures ANCOVAs. The dependent variables were as follows: the logarithmically transformed levels of total power (LnTP), high frequency power (LnHF), the ratio between low and high frequency power (LnLF/HF) and salivary cortisol (LnCortisol). RESULTS: For women, high social status was associated with high LnTP, high LnHF, and low LnLF/HF. In work, lack of control was associated with low LnTP, and lack of support was associated with an increased LnLF/HF ratio. For men, high social status was associated with low LnTP, low LnHF and high LnCortisol. Greater number of hours spent doing housework was associated with both low LnLF/HF and low LnCortisol, whereas a large imbalance between effort and reward was associated with low LnTP and high LnCortisol. CONCLUSION: Despite the small sample size, this study demonstrated that psychosocial factors impact levels of activity in the allostatic systems. PMID- 21034784 TI - A test of four EOG correction methods using an improved validation technique. AB - A group of methods that are employed for removing ocular artifact from the electroencephalogram (EEG) is referred to as electrooculogram (EOG) correction methods. These use least-square linear regression, and the relative success of these is yet to be established. Improving on previous EOG correction validation studies, we present a new validation technique (with greater face validity) and use it to compare four commonly employed EOG correction methods. Data consisted of ERP traces to auditory stimuli that were embedded in up, down, left and right eye movements (EMs), recorded from 24 subjects. A 'Peak Difference' validation measure was employed, which determined the magnitude of the difference of two auditory N100 peaks (those associated with EMs with opposing polarities). All correction methods produced data that was better than not correcting at all. EOG correction methods that accounted for vertical EM, horizontal EM and blink artifact separately using separate EOG channels, produced the best corrections, with some further advantage in methods that enhanced signal (EOG) to noise (EEG) ratios when calculating correction coefficients. PMID- 21034785 TI - Mixed culture polyhydroxyalkanoate (PHA) production from volatile fatty acid (VFA)-rich streams: effect of substrate composition and feeding regime on PHA productivity, composition and properties. AB - In this study, the possibility of manipulating biopolymer composition in mixed culture polyhydroxyalkanoate (PHA) production from fermented molasses was assessed by studying the effects of substrate volatile fatty acid (VFA) composition and feeding regime (pulse wise versus continuous). It was found that the use of a continuous feeding strategy rather than a pulse feeding strategy can not only help mitigate the process constraints of the pulse-feeding strategy (resulting in higher specific and volumetric productivities) but also be used as means to broaden the range of polymer structures. Continuous feeding increased the hydroxyvalerate content by 8% relatively to that obtained from the same feedstock using pulse wise feeding. Therefore, the feeding strategy can be used to manipulate polymer composition. Furthermore, the range of PHA compositions, copolymers of P(HB-co-HV) with HV fraction ranging from 15 to 39%, obtained subsequently resulted in different polymer properties. Increasing HV content resulted in a decrease of the average molecular weight, the glass transition and melting temperatures and also in a reduction in the crystallinity degree from a semi-crystalline material to an amorphous matrix. PMID- 21034786 TI - Importance of stability study of continuous systems for ethanol production. AB - Fuel ethanol industry presents different problems during bioreactors operation. One of them is the unexpected variation in the output ethanol concentration from the bioreactor or a drastic fall in the productivity. In this paper, a compilation of concepts and relevant results of several experimental and theoretical studies about dynamic behavior of fermentation systems for bioethanol production with Saccharomyces cerevisiae and Zymomonas mobilis is done with the purpose of understanding the stability phenomena that could affect the productivity of industries producing fuel ethanol. It is shown that the design of high scale biochemical processes for fuel ethanol production must be done based on stability studies. PMID- 21034787 TI - Comparative requirements for exploratory clinical trials -- eIND, eCTA and microdosing. AB - Exploratory clinical trials provide a strategy for rapid human entry of investigational drugs. Such clinical studies are typically conducted during early clinical development in phase I as first-in-human studies, have no therapeutic intent, are not intended to examine clinical tolerability and involve a small number of human subjects at limited dose/exposure. Early decision data derived from such clinical studies may include PK, PD and/or biomarker-based translational medicine endpoints as well as PK/PD modeling approaches. This review critically discusses the various exploratory clinical trial strategies, their advantages and disadvantages as well as the regulatory safety requirements. In this respect, strategies for exploratory Investigational New Drugs (eIND), exploratory Clinical Trial Applications (eCTA) and microdosing are highlighted and compared in view of the new ICH M3(R2) guideline including options for biotechnology-derived pharmaceuticals such as monoclonal antibodies. PMID- 21034788 TI - Intact cannabinoid CB1 receptors in the Alzheimer's disease cortex. AB - The cannabinoid CB1 receptor has gained much attention as a potential pharmacotherapeutic target in various neurodegenerative diseases including Alzheimer's disease (AD). However, the relation of CB1 receptors to cognitive function in AD is at present unclear. In this study, postmortem brain tissues from a cohort of prospectively assessed, neuropathologically confirmed AD patients and aged controls were used to measure CB1 receptors by immunoblotting, and a subset of subjects also had [(3)H]SR141716A binding. Correlational analyses were then performed for the neurochemical and cognitive data. We found that CB1 receptor levels in were unchanged AD in the brain regions assessed (frontal cortex, anterior cingulate gyrus, hippocampus, caudate nucleus). Within the AD group, frontal cortical CB1 immunoreactivity correlated with cognitive scores assessed within a year of death. Our study suggests that CB1 receptors are intact in AD and may play a role in preserving cognitive function. Therefore, CB1 receptors should be further assessed as a potential therapeutic target in AD. PMID- 21034789 TI - Psychopharmacology in autism: an update. AB - Autism spectrum disorders are characterized by impairment in social reciprocity, disturbances in language and communication, restricted interests and repetitive behaviors of various types, as defined by the DSM-IV. The neurobiological bases of these disorders are poorly understood, although several abnormalities have been found. Pharmacotherapy in autism spectrum disorders lacks a solid, reliable neurobiological basis and at present it is mainly directed at the so-called associated behavioral symptoms, with limited relevance to core symptoms. Atypical neuroleptics, especially risperidone, have been shown to be useful in the treatment of behavioral symptoms in autism. Recent trials with SSRIs did not show remarkable results, in spite of their promising potential role. Attention deficit and hyperactivity disorder medications may be useful for counteracting the additional features of hyperactivity and short attention span. Antiepileptics have shown promising results but there are no specific indications for them as of yet. Research is now directed at evaluating novel treatments and combined behavioral and pharmacologic treatments, since behavioral interventions are the mainstay of the early treatment of autism. An update of currently available pharmacological treatments is provided. PMID- 21034790 TI - Effects of 8-methylguanine on structure, stability and kinetics of formation of tetramolecular quadruplexes. AB - Tetramolecular G-quadruplexes result from the association of four guanine-rich strands. Modification of the backbone strand or the guanine bases of the oligonucleotide may improve stability or introduce new functionalities. In this regard, the 8 position of a guanosine is particularly suitable for introduction of modifications since as it is positioned in the groove of the quadruplex structure. Modifications at this position should not interfere with structural assembly as would changes at Watson-Crick and Hoogsteen sites. In this study, we investigated the effect of an 8-methyl-2'-deoxyguanosine residue (M) on the structure and stability of tetramolecular parallel G-quadruplexes. In some cases, the presence of this residue resulted in the formation of unusual quadruplex structures containing all-syn tetrads. Furthermore, the modified nucleoside M at the 5'-end of the sequence accelerated quadruplex formation by 15-fold or more relative to the unmodified oligonucleotide, which makes this nucleobase an attractive replacement for guanine in the context of tetramolecular parallel quadruplexes. PMID- 21034792 TI - Increased default mode network connectivity associated with meditation. AB - Areas associated with the default mode network (DMN) are substantially similar to those associated with meditation practice. However, no studies on DMN connectivity during resting states have been conducted on meditation practitioners. It was hypothesized that meditators would show heightened functional connectivity in areas of cortical midline activity. Thirty-five meditation practitioners and 33 healthy controls without meditation experience were included in this study. All subjects received 4.68-min resting state functional scanning runs. The posterior cingulate cortex and medial prefrontal cortex were chosen as seed regions for the DMN map. Meditation practitioners demonstrated greater functional connectivity within the DMN in the medial prefrontal cortex area (xyz=339-21) than did controls. These results suggest that the long-term practice of meditation may be associated with functional changes in regions related to internalized attention even when meditation is not being practiced. PMID- 21034791 TI - Adult murine bone marrow-derived very small embryonic-like stem cells differentiate into the hematopoietic lineage after coculture over OP9 stromal cells. AB - OBJECTIVE: We recently identified a population of small Sca-1(+)/Lin(-)/CD45(-) cells in adult murine bone marrow that express several epiblast/germ line and pluripotent stem cell markers (e.g., Oct-4 and SSEA-4) that we named "very small embryonic-like stem cells" (VSELs). In this report, we test the hypothesis that VSELs can differentiate along the hemato/lymphopoietic lineage. MATERIALS AND METHODS: Purified from bone marrow, VSELs were primed/cocultured over OP9 stroma cell line and subsequently tested in vitro and in vivo assays for their hematopoietic potential. In parallel, cells derived from VSELs were evaluated for expression of hematopoietic genes and surface markers. RESULTS: Although we observed that freshly isolated VSELs do not exhibit in vitro and in vivo hematopoietic potential, they may, after coculture over OP9 stromal cells, differentiate along the hematopoietic lineage in a similar way as embryonic stem cells or inducible pluripotent stem cells. "OP9-primed," VSEL-derived cells acquired expression of several hemato/lymphopoiesis-specific genes and markers, gave rise to hematopoietic colonies in vitro, and protected lethally irradiated mice in both primary and secondary transplant models on transplantation. We also observed that, compared to hematopoietic stem/progenitor cells, VSELs are highly resistant to total body irradiation. CONCLUSIONS: Based on these observations, we postulate that VSELs are the most primitive murine bone marrow-residing population of stem cells that have the potential to become specified into the hematopoietic lineage and may share some of the characteristics of long-term repopulating HSCs. PMID- 21034793 TI - Interleukin-17 deficiency improves locomotor recovery and tissue sparing after spinal cord contusion injury in mice. AB - Following the initial impact, spinal cord injury (SCI) triggers a number of inflammatory responses which can exacerbate tissue damage in the cord and impair functional recovery. The involvement of several pro-inflammatory cytokines in the secondary degenerative mechanisms of SCI has been well established, although the role of interleukin-17 (IL-17) remains unclear. In the present study, we used IL 17 knockout (KO) and C57BL/6J wildtype (WT) mice to investigate the effects of IL 17 deficiency on locomotor recovery, lesion size, glial activation and inflammatory cell response following spinal cord contusion injury. Our results show that compared to WT mice, IL-17 KO mice had a significantly smaller lesion size, corresponding with significantly improved locomotor functional recovery following SCI. At 6 weeks after injury, recruitment of B cells, dendritic cells and neutrophils was significantly lower in IL-17 KO than WT mice, however there was no difference in the presence of activated microglia and reactive astrocytes, in the injured spinal cord. These findings suggest that IL-17 is a mediator of secondary degeneration, which contributes to neuroinflammation and hinders functional recovery, though its actions do not affect glial activation following SCI. PMID- 21034794 TI - Intranasal brain-derived neurotrophic factor protects brain from ischemic insult via modulating local inflammation in rats. AB - Inflammation plays a vital role in the pathogenesis of ischemic stroke. Brain derived neurotrophic factor (BDNF) may protect brain tissues from ischemic injury. In this study, we investigated whether intranasal BDNF exerted neuroprotection against ischemic insult by modulating the local inflammation in rats with ischemic stroke. Rats were subjected to temporary occlusion of the right middle cerebral artery (120 min) and intranasal BDNF or vehicle was adminstrated 2 h after reperfusion. Infarct volume and neuron injury were measured using triphenyltetrazolium chloride, Nissl staining and TUNEL assay, respectively. Microglia were detected by immunohistofluorescence. Tumor necrosis factor-alpha, interleukin10 and mRNAs were evaluated by enzyme-linked immunosorbent assay and real-time quantitative polymerase chain reaction. DNA binding activity of nuclear factor-kappa B was measured by electrophoretic mobility shift assay. BDNF level in brain tissues was markedly raised following intranasal administration. There were more Nissl positive and less TUNEL positive neurons in BDNF group than in control group while intranasal BDNF did not reduce the infarct volume significantly (n=6, 0.27+/-0.04 vs. 0.24+/-0.05, P>0.05). BDNF increased the number of activated microglia (OX-42 positive) and phagocytotic microglia (ED1 positive). BDNF suppressed tumor necrosis factor-alpha and mRNA expression while increasing the interleukin10 and mRNA expression. BDNF also increased DNA-binding activity of nuclear factor-kappa B (n=6, 49.78+/-1.23 vs. 52.89+/-1.64, P<0.05). Our data suggest intranasal BDNF might protect the brain against ischemic insult by modulating local inflammation via regulation of the levels of cellular, cytokine and transcription factor in the experimental stroke. PMID- 21034795 TI - Impact of sound exposure and aging on brain-derived neurotrophic factor and tyrosine kinase B receptors levels in dorsal cochlear nucleus 80 days following sound exposure. AB - Recent studies suggested that acute sound exposure resulting in a temporary threshold shift in young adult animals within a series of maladaptive plasticity changes in central auditory structures. Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, is involved in post-trauma peripheral hair cell and spiral ganglion cell survival and has been shown to modulate synaptic strength in cochlear nucleus following sound exposure. The present study evaluated levels of BDNF and its receptor (tyrosine kinase B, [TrkB]) in the dorsal cochlear nucleus (DCN) following a unilateral moderate sound exposure in young (7-8 months) and aged (28-29 months) Fischer Brown Norway (FBN) rats. Eighty days post-exposure, auditory brainstem response (ABR) thresholds for young exposed rats approached control values while aged exposed rats showed residual permanent threshold shifts (PTS) relative to aged controls. BDNF protein levels were significantly up-regulated by 9% in young exposed fusiform cells ipsilateral to the exposure. BDNF levels in aged sound-exposed fusiform cells increased 31% ipsilateral to the exposure. Protein levels of the BDNF receptor, TrkB, were also significantly increased in aged but not in young sound-exposed DCN fusiform cells. The present findings suggest a relationship between the up-regulation of BDNF/TrkB and the increase in spontaneous and driven activity previously observed for aged and sound-exposed fusiform cells. This might be due to a selective maladaptive compensatory down-regulation of glycinergic inhibition in DCN fusiform cells. PMID- 21034796 TI - A novel, extremely fast, feedback inhibition of glutamate release in the crayfish neuromuscular junction. AB - Feedback inhibition serves to modulate release when neurotransmitter levels in the synaptic cleft are elevated. The "classical" feedback auto-inhibition of neurotransmitter release is predominantly mediated by activation of presynaptic G protein-coupled receptors (GPCRs) and exhibits slow kinetics. In cholinergic and glutamatergic synapses and for focal graded depolarization of the axon terminal, feedback inhibition was found to be voltage-dependent. At high depolarizations, such as the one produced by an action potential, low concentrations of neurotransmitter were insufficient to inhibit release. On the other hand, at higher neurotransmitter concentrations, feedback inhibition was observed also for action potential-evoked release. This finding suggests the presence of an additional mechanism of feedback inhibition that operates also at large presynaptic depolarizations. Using the glutamatergic crayfish neuromuscular junction we discovered a novel, extremely fast, form of feedback inhibition which hampers action potential-evoked release. This novel mechanism is pertussis toxin insensitive, and is activated already 1 ms after flash photolysis producing glutamate concentrations higher than the ones required to activate the classical feedback inhibition. This finding implies that this mechanism is recruited only when glutamate levels in the synaptic cleft are relatively high (after high frequency activation or in pathological conditions). We show that both the classical and this novel mechanism operate under physiological conditions. PMID- 21034797 TI - Functional interaction between medial thalamus and rostral anterior cingulate cortex in the suppression of pain affect. AB - The medial thalamic parafascicular nucleus (PF) and the rostral anterior cingulate cortex (rACC) are implicated in the processing and suppression of the affective dimension of pain. The present study evaluated the functional interaction between PF and rACC in mediating the suppression of pain affect in rats following administration of morphine or carbachol (acetylcholine agonist) into PF. Vocalizations that occur following a brief noxious tailshock (vocalization afterdischarges) are a validated rodent model of pain affect, and were preferentially suppressed by injection of morphine or carbachol into PF. Vocalizations that occur during tailshock were suppressed to a lesser degree, whereas, spinal motor reflexes (tail flick and hindlimb movements) were only slightly suppressed by injection of carbachol into PF and unaffected by injection of morphine into PF. Blocking glutamate receptors in rACC (NMDA and non-NMDA) by injecting D-2-amino-5-phosphonovalerate (AP-5) or 6-cyano-7-nitroquinoxaline-2,3 dione disodium (CNQX) produced dose-dependent antagonism of morphine-induced increases in vocalization thresholds. Carbachol-induced increases in vocalization thresholds were not affected by injection of either glutamate receptor antagonist into rACC. The results demonstrate that glutamate receptors in the rACC contribute to the suppression of pain affect produced by injection of morphine into PF, but not to the suppression of pain affect generated by intra-PF injection of carbachol. PMID- 21034798 TI - Discussion of a well-designed clinical trial which did not demonstrate effectiveness: UIC center for botanical dietary supplements research study of black cohosh and red clover. AB - The performance of a clinical trial for pharmaceutical agents is usually undertaken only after there is likely benefit demonstrated from the use of the putative agent. The consideration of botanical products as pharmaceutical agents must similarly go through a rigorous evaluation process. The present work reviews the recently published phase II study evaluating the effectiveness of black cohosh and red clover in a randomized trial with conjugated equine estradiol/medroxyprogesterone acetate and placebo for the treatment of menopausal symptoms. We analyze the possible reasons why this study failed to show benefit for either botanical product in reducing menopause-related vasomotor symptoms. PMID- 21034799 TI - Isolation and identification of degradation products of salvianolic acid A by NMR and LC-MS. AB - Salvianolic acid A was subjected to thermal degradation condition in distilled water at 90 degrees C. Four degradation products, including two novel compounds (1, 2) and two known ones (5, 6), were isolated by reverse-phase semi-preparative liquid chromatography and identified on the basis of NMR and MS data. Other two degradation products (3, 4) were determined by LC-MS analysis. PMID- 21034800 TI - Elaborations on the Higuchi model for drug delivery. AB - The Higuchi model for the rate of drug release from matrix devices where the drug loading exceeds the solubility in the matrix medium, whose 50-year anniversary is celebrated in this issue, has proven to be a robust framework and an invaluable tool in developing a significant part of the modern controlled drug delivery industry. This paper reviews the conceptual and mathematical bases for this model and some consequences of its inherent assumptions. In addition, selected extensions of the model that have proven useful over the years are summarized. These include the effects of external mass transfer resistance and spatial variations of drug loading. PMID- 21034801 TI - Modelling, solubility and pK(a) of five sparingly soluble drugs. AB - Drug solubility is an important aspect of drug development. The objective of this investigation was to measure solubilities of five drugs (cimetidine, phenylbutazone, fenbufen, nitrofurantoin, triamterene) at constant pH in range of temperature from 270 to 340K in three solvents: water, ethanol and 1-octanol with the dynamic-visual method and the saturation shake-flask method using spectrophotometric analysis. The Barton group contribution method was used for the calculations of molar volumes of solutes. The thermodynamic description of the solubility curves was made using the thermophysical properties obtained with the differential scanning microcalorimetry technique (DSC). The DSC measurements have shown different than existing in the literature enthalpies of melting for phenylbutazone and fenbufen. The experimental solubility data also differ from the literature data, normally measured at one, or two temperatures only. The solubility data have been correlated by means of three commonly known excess Gibbs energy, G(E) equations. The activity coefficients of drugs at saturated solutions were calculated from the experimental data. Reexamination of the pK(a) values using diluted solutions was made with the Bates-Schwarzenbach method for the pK(a) measurements. The association constants and corresponding pK(a) values of drugs were close to the most of the literature data. We hope that our new solubility data, thermophysical data, and pK(a) values will improve all prediction-methods and their precision. PMID- 21034802 TI - Prediction of mechanical properties of compacted binary mixtures containing high dose poorly compressible drug. AB - The aim of the study was to develop, compare and validate predictive model for mechanical property of binary systems. The mechanical properties of binary mixtures of ibuprofen (IBN) a poorly compressible high dose drug, were studied in presence of different excipients. The tensile strength of tablets of individual components viz. IBN, microcrystalline cellulose (MCC), and dicalcium phosphate dihydrate (DCP) and binary mixtures of IBN with excipients was measured at various relative densities. Prediction of the mechanical property of binary mixtures, from that of single components, was attempted using Ryshkewitch Duckworth (R-D) and Percolation theory, by assuming a linear mixing rule or a power law mixing rule. The models were compared, and the best model was proposed based on the distribution of residuals and the Akaike's information criterion. Good predictions were obtained with the power law combined with linear mixing rule, using R-D and Percolation models. The results indicated that the proposed model can well predict the mechanical properties of binary system containing predominantly poorly compressible drug candidate. The predictions of these models and conclusions can be systematically generalized to other pharmaceutical powders. PMID- 21034803 TI - Effects of xiang-fu-si-wu decoction and its main components for dysmenorrhea on uterus contraction. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Xiang-fu-si-wu decoction has been widely used to treat blood stasis syndromes in gynecology diseases, such as primary dysmenorrhea in clinical practice for hundreds of years and show great efficacy. The efficient components and mechanism of action on uterus contraction were seldom reported. AIM OF THE STUDY: The present study was conducted to evaluate the inhibitory effects of active fractions and its main bioactive components of xiang-fu-si-wu decoction on uterine contraction. MATERIALS AND METHODS: Model of non-pregnant mice uterine contraction induced by oxytocin was used to evaluate activity. Levels of Ca(2+) and nitric oxide (NO) in primary dysmenorrheal model mice uterus were also been detected. Components in active fraction were identified and quantified by HPLC-DAD. RESULTS AND CONCLUSIONS: It was found the active fraction of xiang-fu-si-wu decoction may become potential Ca(2+) channel blocking agents. Alkaloids like berberine were main active components in bioactive fraction of xiang-fu-si-wu decoction for dysmenorrhea on uterus contraction. PMID- 21034804 TI - Safety evaluation of tea (Camellia sinensis (L.) O. Kuntze) flower extract: assessment of mutagenicity, and acute and subchronic toxicity in rats. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Tea (Camellia sinensis (L.) O. Kuntze, Theaceae) flowers possess many physiological functions and have been used in traditional medicines for deodorization, skin care, cough suppressant and expectorant in China. However, there is a little information about its possible toxicity. AIM OF THE STUDY: The present investigation was carried out to evaluate the safety of tea flower extract by mutagenicity and acute and subchronic toxicity studies. MATERIALS AND METHODS: Mutagenicity of tea flower extract was evaluated by the Ames test in Salmonella typhimurium strains TA97, TA98, TA100 and TA102 at concentrations of 0.008, 0.04, 0.2, 1.0, 5.0 mg/plate. In the acute toxicity study, Sprague-Dawley rats were administered a single dose of 12.0 g/kg of body weight by gavage, and were monitored for 14 days. In the subchronic toxicity study, tea flower extract was administered by gavage at doses of 1.0, 2.0 and 4.0 g/kg body weight daily for 13 weeks to Sprague-Dawley rats. RESULTS: In the Ames test, there was no mutagenic effect of tea flower extract (up to 5.0 mg/plate) towards four tested strains (TA97, TA98, TA100, TA102), with or without metabolic activation (S9). In the acute toxicity study, all animals gained weight and appeared active and normal, so the LD(50) value must be >12.0 g/kg body weight. In the subchronic toxicity study, no dose-related effects on survival, growth, hematology, blood chemistry, organ weights, or pathologic lesions were observed. CONCLUSION: These results indicate that tea flower extract does not possess mutagenic potential, and that both acute and subchronic toxicity towards animals is very low. A no-observed adverse-effect level (NOAEL) for tea flower extract is 4.0 g/kg bw/day for rats under the conditions of this study. PMID- 21034805 TI - Advances in carbon nanotube based electrochemical sensors for bioanalytical applications. AB - Electrochemical (EC) sensing approaches have exploited the use of carbon nanotubes (CNTs) as electrode materials owing to their unique structures and properties to provide strong electrocatalytic activity with minimal surface fouling. Nanofabrication and device integration technologies have emerged along with significant advances in the synthesis, purification, conjugation and biofunctionalization of CNTs. Such combined efforts have contributed towards the rapid development of CNT-based sensors for a plethora of important analytes with improved detection sensitivity and selectivity. The use of CNTs opens an opportunity for the direct electron transfer between the enzyme and the active electrode area. Of particular interest are also excellent electrocatalytic activities of CNTs on the redox reaction of hydrogen peroxide and nicotinamide adenine dinucleotide, two major by-products of enzymatic reactions. This excellent electrocatalysis holds a promising future for the simple design and implementation of on-site biosensors for oxidases and dehydrogenases with enhanced selectivity. To date, the use of an anti-interference layer or an artificial electron mediator is critically needed to circumvent unwanted endogenous electroactive species. Such interfering species are effectively suppressed by using CNT based electrodes since the oxidation of NADH, thiols, hydrogen peroxide, etc. by CNTs can be performed at low potentials. Nevertheless, the major future challenges for the development of CNT-EC sensors include miniaturization, optimization and simplification of the procedure for fabricating CNT based electrodes with minimal non-specific binding, high sensitivity and rapid response followed by their extensive validation using "real world" samples. A high resistance to electrode fouling and selectivity are the two key pending issues for the application of CNT-based biosensors in clinical chemistry, food quality and control, waste water treatment and bioprocessing. PMID- 21034806 TI - Classifying DNA assembly protocols for devising cellular architectures. AB - DNA assembly is one of the most fundamental techniques in synthetic biology. Efficient methods can turn traditional DNA cloning into time-saving and higher efficiency practice, which is a foundation to accomplish the dreams of synthetic biologists for devising cellular architectures, reprogramming cellular behaviors, or creating synthetic cells. In this review, typical strategies of DNA assembly are discussed with special emphasis on the assembly of long and multiple DNA fragments into intact plasmids or assembled compositions. Constructively, all reported strategies were categorized into in vivo and in vitro types, and protocols are presented in a functional and practice-oriented way in order to portray the general nature of DNA assembly applications. Significantly, a five step blueprint is proposed for devising cell architectures that produce valuable chemicals. PMID- 21034807 TI - Combined developmental toxicity of bisphenol A and genistein in micromass cultures of rat embryonic limb bud and midbrain cells. AB - Bisphenol A (BPA), widely used in industry and dentistry, and genistein (GEN), the predominant component of soy product, are both known environmental estrogen. In the present study, we investigated the developmental toxicity of BPA and GEN and their combined effect using micromass test, which is one of three standard alternative developmental toxicity tests recommended by European Center for the Validation of Alternative Methods (ECVAM). The results showed that IC50-P (cell proliferation) and IC50-D (cell differentiation) of BPA and GEN were approximately 20 and 5 MUg/ml, respectively. No observed adverse effect level (NOAEL) of BPA and GEN were 10 and 0.94 MUg/ml, respectively. The manifestation of BPA as a teratogen was insufficient, although the "low dose" effect should be paid attention to. While the evidence of GEN as a teratogen was solid, especially with the consideration of "high dose" application in clinical treatment. The combined effect of BPA and GEN was generally additive action except that in MB proliferation. PMID- 21034808 TI - The identification of cellular targets of 17beta estradiol using a lytic (T7) cDNA phage display approach. AB - To unravel the mechanism of action of chemical compounds, it is crucial to know their cellular targets. A novel in vitro tool that can be used as a fast, simple and cost effective alternative is cDNA phage display. This tool is used in our study to select cellular targets of 17beta estradiol (E2). It was possible to select two potential cellular targets of E2 out of the T7 SelectTM Human Breast cDNA phage library. The selected cellular targets, autophagy/beclin-1 regulator 1 (beclin 1) and ATP synthase F(0) subunit 6 (ATP6) have so far been unknown as binding proteins of E2. To confirm the E2 binding properties of these selected proteins, surface plasmon resonance (SPR) was used. With SPR the K(d) values were determined to be 0.178+/-0.031 and 0.401+/-0.142 nM for the ATP6 phage and beclin 1 phage, respectively. These K(d) values in the low nM range verify that the selected cellular proteins are indeed binding proteins for E2. The selection and identification of these two potential cellular targets of E2, can enhance our current understanding of its mechanism of action. This illustrates the potential of lytic (T7) cDNA phage display in toxicology, to provide important information about cellular targets of chemical compounds. PMID- 21034809 TI - beta-Amyloid peptide increases levels of iron content and oxidative stress in human cell and Caenorhabditis elegans models of Alzheimer disease. AB - Recent studies indicate that the deposition of beta-amyloid peptide (Abeta) is related to the pathogenesis of Alzheimer disease (AD); however, the underlying mechanism is still not clear. The abnormal interactions of Abeta with metal ions such as iron are implicated in the process of Abeta deposition and oxidative stress in AD brains. In this study, we observed that Abeta increased the levels of iron content and oxidative stress in SH-SY5Y cells overexpressing the Swedish mutant form of human beta-amyloid precursor protein (APPsw) and in Caenorhabditis elegans Abeta-expressing strain CL2006. Intracellular iron and calcium levels and reactive oxygen species and nitric oxide generation significantly increased in APPsw cells compared to control cells. The activity of superoxide dismutase and the antioxidant levels of APPsw cells were significantly lower than those of control cells. Moreover, iron treatment decreased cell viability and mitochondrial membrane potential and aggravated oxidative stress damage as well as the release of Abeta1-40 from the APPsw cells. The iron homeostasis disruption in APPsw cells is very probably associated with elevated expression of the iron transporter divalent metal transporter 1, but not transferrin receptor. Furthermore, the C. elegans with Abeta-expression had increased iron accumulation. In aggregate, these results demonstrate that Abeta accumulation in neuronal cells correlated with neuronal iron homeostasis disruption and probably contributed to the pathogenesis of AD. PMID- 21034811 TI - Reactivity of hydrogen sulfide with peroxynitrite and other oxidants of biological interest. AB - Hydrogen sulfide (H(2)S) is an endogenously generated gas that can also be administered exogenously. It modulates physiological functions and has reported cytoprotective effects. To evaluate a possible antioxidant role, we investigated the reactivity of hydrogen sulfide with several one- and two-electron oxidants. The rate constant of the direct reaction with peroxynitrite was (4.8+/ 1.4)*10(3)M(-1) s(-1) (pH 7.4, 37 degrees C). At low hydrogen sulfide concentrations, oxidation by peroxynitrite led to oxygen consumption, consistent with a one-electron oxidation that initiated a radical chain reaction. Accordingly, pulse radiolysis studies indicated that hydrogen sulfide reacted with nitrogen dioxide at (3.0+/-0.3)*10(6)M(-1) s(-1) at pH 6 and (1.2+/ 0.1)*10(7)M(-1) s(-1) at pH 7.5 (25 degrees C). The reactions of hydrogen sulfide with hydrogen peroxide, hypochlorite, and taurine chloramine had rate constants of 0.73+/-0.03, (8+/-3)*10(7), and 303+/-27M(-1) s(-1), respectively (pH 7.4, 37 degrees C). The reactivity of hydrogen sulfide was compared to that of low molecular-weight thiols such as cysteine and glutathione. Considering the low tissue concentrations of endogenous hydrogen sulfide, direct reactions with oxidants probably cannot completely account for its protective effects. PMID- 21034810 TI - alpha-Lipoic acid ameliorates foam cell formation via liver X receptor alpha dependent upregulation of ATP-binding cassette transporters A1 and G1. AB - alpha-Lipoic acid (alpha-LA), a key cofactor in cellular energy metabolism, has protective activities in atherosclerosis, yet the detailed mechanisms are not fully understood. In this study, we examined whether alpha-LA affects foam cell formation and its underlying molecular mechanisms in murine macrophages. Treatment with alpha-LA markedly attenuated oxidized low-density lipoprotein (oxLDL)-mediated cholesterol accumulation in macrophages, which was due to increased cholesterol efflux. Additionally, alpha-LA treatment dose-dependently increased protein levels of ATP-binding cassette transporter A1 (ABCA1) and ABCG1 but had no effect on the protein expression of SR-A, CD36, or SR-BI involved in cholesterol homeostasis. Furthermore, alpha-LA increased the mRNA expression of ABCA1 and ABCG1. The upregulation of ABCA1 and ABCG1 by alpha-LA depended on liver X receptor alpha (LXRalpha), as evidenced by an increase in the nuclear levels of LXRalpha and LXRE-mediated luciferase activity and its prevention of the expression of ABCA1 and ABCG1 after inhibition of LXRalpha activity by the pharmacological inhibitor geranylgeranyl pyrophosphate (GGPP) or knockdown of LXRalpha expression with small interfering RNA (siRNA). Consistently, alpha-LA mediated suppression of oxLDL-induced lipid accumulation was abolished by GGPP or LXRalpha siRNA treatment. In conclusion, LXRalpha-dependent upregulation of ABCA1 and ABCG1 may mediate the beneficial effect of alpha-LA on foam cell formation. PMID- 21034812 TI - 3,3'-Diindolylmethane decreases VCAM-1 expression and alleviates experimental colitis via a BRCA1-dependent antioxidant pathway. AB - Reactive oxygen species (ROS) exhibit a key role in the pathogenesis of inflammatory bowel disease (IBD). 3,3'-Diindolylmethane (DIM) can protect against oxidative stress in a breast cancer susceptibility gene 1 (BRCA1)-dependent manner. The aim of this study was to examine the therapeutic effects of DIM in experimental colitis and investigate the possible mechanisms underlying its effects on intestinal inflammation. The therapeutic effects of DIM were studied in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis. Pathological markers of colitis severity, antioxidant activity, and ROS generation in colonic tissue were measured. The impact of DIM on ROS-induced endothelial vascular cell adhesion molecule 1 (VCAM-1) expression and leukocyte-endothelial cell interaction was further investigated in cultures of endothelial cells and in the TNBS-induced colitis model. Administration of DIM was demonstrated to attenuate experimental colitis, as judged by pathological indices. DIM could effectively stimulate the expression of BRCA1 in vitro and in vivo and reduce ROS generation, leading to the inhibition of VCAM-1 expression and leukocyte-endothelial cell adhesion, and finally resulted in an alleviation of experimental colitis. DIM has shown anti-IBD activity in animal models by inhibiting ROS-induced VCAM-1 expression and leukocyte recruitment via a BRCA1-dependent antioxidant pathway and thus may offer potential treatments for IBD patients. PMID- 21034814 TI - Reconciling an archaeal origin of eukaryotes with engulfment: a biologically plausible update of the Eocyte hypothesis. AB - An archaeal origin of eukaryotes is often equated with the engulfment of the bacterial ancestor of mitochondria by an archaeon. Such an event is problematic in that it is not supported by archaeal cell biology. We show that placing phylogenetic results within a stem-and-crown framework eliminates such incompatibilities, and that an archaeal origin for eukaryotes (as suggested from recent phylogenies) can be uncontroversially reconciled with phagocytosis as the mechanism for engulfment of the mitochondrial ancestor. This is significant because it eliminates a perceived problem with eukaryote origins: that an archaeal origin of eukaryotes (as under the Eocyte hypothesis) cannot be reconciled with existing cell biological mechanisms through which bacteria may take up residence inside eukaryote cells. PMID- 21034815 TI - On the last common ancestor and early evolution of eukaryotes: reconstructing the history of mitochondrial ribosomes. AB - Understanding early evolution is a major challenge for the post-genomic era. A promising way to tackle this issue is to analyze the evolutionary history of key cellular systems through phylogenomic approaches. The current availability of genomic data from representatives of diverse lineages (especially eukaryotes), together with the ever growing number of proteomic characterizations now provides ample material to apply this type of analyses to trace back the origin and evolution of the three domains of life. Here, we have reconstructed the composition of the ancestral mitochondrial ribosome in the Last Eukaryotic Common Ancestor (LECA) and investigated its subsequent evolution in six major eukaryotic supergroups. We infer that LECA possessed a mitochondrial ribosome that was already much larger than its bacterial ancestor, with 19 additional specific proteins, indicating that a certain amount of time occurred between initial endosymbiosis at the origin of the mitochondrion and the diversification of present-day eukaryotic supergroups. Subsequently, mitochondrial ribosomes appear to have undergone a very dynamic evolutionary history in the different eukaryotic lineages, involving the loss of different sets of ribosomal protein-coding genes, their transfer to the host genome, as well as the acquisition of many novel components. This chaotic history for a such fundamental cellular machinery is puzzling, especially when compared to cytosolic, bacterial or chloroplastic ribosomes, which are much more stable. Intriguingly, archaeal ribosomes also show a very dynamic nature, with multiple independent losses among lineages. PMID- 21034816 TI - Isoprenoid biosynthesis in Archaea--biochemical and evolutionary implications. AB - Isoprenoids are indispensable for all types of cellular life in the Archaea, Bacteria, and Eucarya. These membrane-associated molecules are involved in a wide variety of vital biological functions, ranging from compartmentalization and stability, to protection and energy-transduction. In Archaea, isoprenoid compounds constitute the hydrophobic moiety of the typical ether-linked membrane lipids. With respect to stereochemistry and composition, these archaeal lipids are very different from the ester-linked, fatty acid-based phospholipids in bacterial and eukaryotic membranes. This review provides an update on isoprenoid biosynthesis pathways, with a focus on the archaeal enzymes. The black-and-white distribution of fundamentally distinct membrane lipids in Archaea on the one hand, and Bacteria and Eucarya on the other, has previously been used as a basis for hypothetical evolutionary scenarios, a selection of which will be discussed here. PMID- 21034813 TI - Mechanism-based therapeutic approaches to rhabdomyolysis-induced renal failure. AB - Rhabdomyolysis-induced renal failure represents up to 15% of all cases of acute renal failure. Many studies over the past 4 decades have demonstrated that accumulation of myoglobin in the kidney is central in the mechanism leading to kidney injury. However, some discussion exists regarding the mechanism mediating this oxidant injury. Although the free-iron-catalyzed Fenton reaction has been proposed to explain the tissue injury, more recent evidence strongly suggests that the main cause of oxidant injury is myoglobin redox cycling and generation of oxidized lipids. These molecules can propagate tissue injury and cause renal vasoconstriction, two of the three main conditions associated with acute renal failure. This review presents the evidence supporting the two mechanisms of oxidative injury, describes the central role of myoglobin redox cycling in the pathology of renal failure associated with rhabdomyolysis, and discusses the value of therapeutic interventions aiming at inhibiting myoglobin redox cycling for the treatment of rhabdomyolysis-induced renal failure. PMID- 21034817 TI - A new fusion hypothesis for the origin of Eukarya: better than previous ones, but probably also wrong. AB - I discuss here the possibility that Eukarya originated from the engulfment of a thaumarchaeon by a PCV (Planctomycetes, Verrucomicrobia, Chlamydiae) bacterium, followed by invasions of NCLDV and retroviruses. The thaumarchaeon provided both informational and operational proteins (actins, ESCRT proteins), including some essential proteins absent in other archaeal phyla (Topo IB), whereas the PVC bacterium provided phospholipids, tubulin and the membrane coat proteins required for the formation of the nucleus. Viral invasions introduced many proteins that are specific to modern Eukarya and produced an arms race that favoured the evolution of Eukarya toward increasing complexity. This scenario is the best possible fusion hypothesis that can be presently proposed. However, it still requires several ad hoc assumptions to explain the origin of the nucleus and the distribution pattern of archaeal and bacterial traits in modern Eukarya. Furthermore, it still fails to explain convincingly the origin of eukaryal viruses and the existence of three distinct lineages of ribosomes. I conclude that Eukarya and their viruses more probably evolved from a specific lineage, according to the three domains scenario originally proposed by Carl Woese. PMID- 21034818 TI - Evolution of the Archaea: emerging views on origins and phylogeny. AB - Of the three domains of life, the Archaea are the most recently discovered and, from the perspective of systematics, perhaps the least understood. More than three decades after their discovery, there is still no overwhelming consensus as to their phylogenetic status, with diverse evidence supporting in varying degrees their monophyly, paraphyly, or even polyphyly. As a further complication, their evolutionary history is inextricably linked to the origin of Eukarya, one of the most challenging problems in evolutionary biology. This exclusive relationship between the eukaryal nucleocytoplasm and the Archaea is further supported by a new methodology for rooting the ribosomal Tree of Life based on amino acid composition. Novel approaches such as utilizing horizontal gene transfers as synchronizing events and branch length analysis of deep paralogs will help to clarify temporal relationships between these lineages, and may prove useful in evaluating the numerous conflicting hypotheses related to the evolution of the Archaea and Eukarya. PMID- 21034819 TI - Some considerations on the nature of LUCA, and the nature of life. AB - In addition to its scientific interest, research on the last universal common ancestor (LUCA) and the lower part of the tree of life raises important and difficult issues in biology, but also in the philosophy of science as well as in philosophy in general. The way inquiries are formulated has to be scrutinized to avoid unanswerable questions. Preconceived ideas, poorly defined notions and abuse of metaphors are obstacles which can induce bias in studies and in the interpretation of their results. In the background, the question of life has recently re-emerged. PMID- 21034820 TI - Sulfate esters of morphine derivatives: synthesis and characterization. AB - Sixteen 3-O- and 6-O-sulfate esters of morphine, codeine and some of their N methyl quaternary derivatives were synthesized by means of sulfation with pyridine-SO(3) complex and sulfuric acid/N,N'-dicyclohexylcarbodiimide. Complete (1)H- and (13)C-NMR assignments are given for each of the synthesized compounds based on one- and two-dimensional homo- and heteronuclear measurements. Comparative analysis of chiral properties by circular dichroism and optical rotatory dispersion revealed characteristic differences in the spectra due to changes in charge, polarity and intramolecular association by strong hydrogen bonds in aqueous solution. The synthesized sulfate esters are prospective peripheral analgesics lacking central side effects and are also useful as reference substances for various analytical studies involving sulfate ester metabolites. PMID- 21034821 TI - Type XVII collagen (BP180) can function as a cell-matrix adhesion molecule via binding to laminin 332. AB - Collagen XVII (COL17) is a transmembrane glycoprotein that is expressed on the basal surface of basal epidermal keratinocytes. Previous observations have led to the hypothesis that an interaction between COL17 and laminin 332, an extracellular matrix protein, contributes to the attachment of the basal keratinocyte to the basement membrane. In order to isolate and manipulate COL17 interactions with ECM components, we induced COL17 expression in two cells lines, SK-MEL1 and K562, that exhibit little or no capacity to attach to our test substrates, including laminin 332, types I and IV collagen, and fibronectin. Cells expressing high levels of COL17 preferentially adhered to a laminin 332 matrix, and, to a lesser extent, type IV collagen, while showing little or no binding to type I collagen or fibronectin. A quantitative analysis of cell adhesive forces revealed that, compared with COL17-negative cells, COL17-positive cells required over 7-fold greater force to achieve 50% detachment from a laminin 332 substrate. When a cell preparation (either K562 or SK-MEL1) with heterogeneous COL17 expression levels was allowed to attach to a laminin 332 matrix, the COL17-positive and COL17-negative cells differentially sorted to the bound and unbound cell fractions, respectively. COL17-dependent attachment to laminin 332 could be reduced or abolished by siRNA-mediated knock-down of COL17 expression or by adding to the assay wells specific antibodies against COL17 or laminin 332. These findings provide strong support for the hypothesis that cell surface COL17 can interact with laminin 332 and, together, participate in the adherence of a cell to the extracellular matrix. PMID- 21034822 TI - Respiratory tract immunization of non-human primates with a Newcastle disease virus-vectored vaccine candidate against Ebola virus elicits a neutralizing antibody response. AB - We previously developed a respiratory tract vaccine candidate against Ebola virus (EBOV) based on human parainfluenza virus type 3 (HPIV3), a respiratory paramyxovirus, expressing the EBOV GP envelope protein (HPIV3/GP) from an added gene. Two doses of this vaccine candidate delivered by the intranasal and intratracheal route protected monkeys against intraperitoneal challenge with EBOV; however, concerns exist that the vaccine candidate may have reduced immunogenicity in the adult human population due to pre-existing immunity against HPIV3. Here we developed a new vaccine candidate (NDV/GP) based on Newcastle disease virus (NDV), an avian paramyxovirus that is antigenically distinct from human viral pathogens and is highly attenuated in monkeys. Following one intranasal and intratracheal inoculation of Rhesus monkeys with NDV/GP, titers of EBOV-specific antibodies in respiratory tract secretions and serum samples determined by ELISA, as well as serum EBOV-neutralizing antibodies, were undetectable or low compared to those induced by HPIV3/GP. A second immunization resulted in a substantial boost in serum IgG ELISA titers, yet the titers remained lower than those induced by a second dose of HPIV3/GP. In contrast, the ELISA IgA titers in respiratory tract secretions and, more importantly, the serum EBOV-neutralizing antibody titers were equal to those induced after the second dose of HPIV3/GP. These data suggest that NDV/GP can be effective for immunization against EBOV alone, or in combination with either HPIV3/GP or another vaccine platform in a heterologous prime-boost regimen. PMID- 21034823 TI - Imperfect vaccine-induced immunity and whooping cough transmission to infants. AB - Whooping cough, caused by B. pertussis and B. parapertussis, has increased in incidence throughout much of the developed world since the 1980s despite high vaccine coverage, causing an increased risk of infection in infants who have substantial disease-induced mortality. Duration of immunity and epidemically significant routes of transmission across age groups remain unclear and deserve further investigation to inform vaccination strategies to better control pertussis burden. The authors analyze age- and species-specific whooping cough tests and vaccine histories in Massachusetts from 1990 to 2008. On average, the disease-free duration is 10.5 years. However, it has been decreasing over time, possibly due to a rising force of infection through increased circulation. Despite the importance of teenage cases during epidemics, wavelet analyses suggest that they are not the most important source of transmission to infants. In addition, the data indicate that the B. pertussis vaccine is not protective against disease induced by B. parapertussis. PMID- 21034824 TI - A replication defective recombinant Ad5 vaccine expressing Ebola virus GP is safe and immunogenic in healthy adults. AB - Ebola virus causes irregular outbreaks of severe hemorrhagic fever in equatorial Africa. Case mortality remains high; there is no effective treatment and outbreaks are sporadic and unpredictable. Studies of Ebola virus vaccine platforms in non-human primates have established that the induction of protective immunity is possible and safety and human immunogenicity has been demonstrated in a previous Phase I clinical trial of a 1st generation Ebola DNA vaccine. We now report the safety and immunogenicity of a recombinant adenovirus serotype 5 (rAd5) vaccine encoding the envelope glycoprotein (GP) from the Zaire and Sudan Ebola virus species, in a randomized, placebo-controlled, double-blinded, dose escalation, Phase I human study. Thirty-one healthy adults received vaccine at 2*10(9) (n=12), or 2*10(10) (n=11) viral particles or placebo (n=8) as an intramuscular injection. Antibody responses were assessed by ELISA and neutralizing assays; and T cell responses were assessed by ELISpot and intracellular cytokine staining assays. This recombinant Ebola virus vaccine was safe and subjects developed antigen specific humoral and cellular immune responses. PMID- 21034825 TI - A single immunization near birth elicits immediate and lifelong protective immunity. AB - Most existing vaccines do not induce protective immunity immediately following birth, nor do they retain protective efficacy in the latter years of life without booster doses. Using a mouse model, we present evidence that a live-replicating vaccine administered only once shortly after birth was able to induce both immediate and lifelong protection. Newborn mice immunized with a safe, highly attenuated strain of Listeria monocytogenes (Lm) were already protected by day 7 post-vaccination when challenged with a virulent strain of Lm. Furthermore, all mice remained fully protected for 2 years after only a single immunization. Vaccine-specific T cell immune responses were still detectable 2 years later, indicating long-lived immune memory even in neonatal vaccine recipients. Analysis of memory precursor subsets, specific for antigens homologous to Lm or a model vaccine (Ova), demonstrated remarkable similarity between adult and neonatal vaccine recipient effector and central memory CD8 T cell development. The magnitude of expansion of antigen specific memory T cells post-infectious challenge correlated with protection in both groups. This is the first direct evidence that vaccination--even in the absence of a booster dose--is capable of inducing immediate and lifelong protective immune memory regardless of age at the time of initial vaccination. PMID- 21034826 TI - Biopolymer encapsulated live influenza virus as a universal CD8+ T cell vaccine against influenza virus. AB - Current influenza virus vaccines primarily elicit antibodies and can be rendered ineffective by antigenic drift and shift. Vaccines that elicit CD8+ T cell responses targeting less variable proteins may function as universal vaccines that have broad reactivity against different influenza virus strains. To generate such a universal vaccine, we encapsulated live influenza virus in a biopolymer and delivered it to mice subcutaneously. This vaccine was safe, induced potent CD8+ T cell immunity and protected mice against heterosubtypic lethal challenge. Safety of subcutaneous (SQ) vaccination was tested in Rag-/-gammac-/- double knockout mice which we show cannot control intranasal infection. Biopolymer encapsulation of live influenza virus could be used to develop universal CD8+ T cell vaccines against heterosubtypic and pandemic strains. PMID- 21034827 TI - MIS416, a non-toxic microparticle adjuvant derived from Propionibacterium acnes comprising immunostimulatory muramyl dipeptide and bacterial DNA promotes cross priming and Th1 immunity. AB - Propionibacterium acnes was modified using biochemical extraction methods generating a suspension of microparticles (MIS416) comprising a minimal cell wall skeleton rich in immunostimulatory crosslinked muramyl dipeptide repeats and native bacterial DNA fragments, each which have known adjuvant activity. In vitro studies demonstrated that MIS416 was readily internalized by human myeloid and plasmacytoid DC inducing cytokine secretion and cell activation/maturation. Vaccination studies in mice using OVA as a model antigen demonstrated that MIS416 acts as a Th1 adjuvant, promoting cross-priming of cytotoxic CD8(+) T cell responses and enhanced anti-tumour immunity. Covalent attachment of OVA to MIS416 enabling simultaneous delivery of antigen and adjuvant to the antigen presentation system resulted in a dose-sparing vaccine formulation. Preclinical GLP toxicology studies demonstrated that MIS416 has a favorable safety profile in mouse and rabbit supporting its use in human vaccine formulations. PMID- 21034829 TI - Vaccination with a modified-live bovine viral diarrhea virus (BVDV) type 1a vaccine completely protected calves against challenge with BVDV type 1b strains. AB - Vaccination plays a significant role in the control of bovine viral diarrhea virus (BVDV) infection and spread. Recent studies revealed that type 1b is the predominant BVDV type 1 subgenotype, representing more than 75% of field isolates of BVDV-1. However, nearly all current, commercially available BVDV type 1 vaccines contain BVDV-1a strains. Previous studies have indicated that anti-BVDV sera, induced by BVDV-1a viruses, show less neutralization activity to BVDV-1b isolates than type 1a. Therefore, it is critically important to evaluate BVDV-1a vaccines in their ability to prevent BVDV-1b infection in calves. In current studies, calves were vaccinated subcutaneously, intradermally or intranasally with a single dose of a multivalent, modified-live viral vaccine containing a BVDV-1a strain, and were challenged with differing BVDV-1b strains to determine the efficacy and duration of immunity of the vaccine against these heterologous virus strains. Vaccinated calves, in all administration routes, were protected from respiratory disease caused by the BVDV-1b viruses, as indicated by significantly fewer clinical signs, lower rectal temperatures, reduced viral shedding and greater white blood cell counts than non-vaccinated control animals. The BVDV-1a vaccine elicited efficacious protection in calves against each BVDV 1b challenge strain, with a duration of immunity of at least 6 months. PMID- 21034828 TI - An adjuvanted pandemic influenza H1N1 vaccine provides early and long term protection in health care workers. AB - Mass vaccination was the most effective prophylaxis for protecting the population during the influenza H1N1 pandemic. We have evaluated the tolerability, immunogenicity and kinetics of the antibody response to a monovalent oil-in-water (AS03) adjuvanted human pandemic split influenza A/California/7/2009 H1N1 (3.75 MUg haemagglutinin) vaccine in health care workers. Vaccination elicited a rapid and early protective level of haemagglutination inhibition antibody from 6 to 7 days post vaccination, and by 14 to 21 days post vaccination, up to 98% of vaccinees had protective antibody titres which persisted for at least 3 months in 84-92% of subjects. A rapid induction of protective antibody is important in reducing community spread of pandemic influenza and in helping maintain the integrity of the health care system during the pandemic. PMID- 21034830 TI - Protective effect of immunosuppressive treatment before orthotopic kidney autotransplantation. AB - BACKGROUND: Ischemia reperfusion injury (IRI) is one of the risk factors for delayed graft function, acute rejection and long term allograft survival after kidney transplantation. IRI is an independent antigen inflammatory process that produces tissue damage. Our objective was to study the impact of immunosuppressive treatment (IS) on IRI applying only one dose of IS before orthotopic kidney autotransplantation. METHODS: Twenty-four rats allocated in four groups were studied. One group served as control (G1: autotransplanted rats without IS) and the rest received IS 12 h before kidney autotransplantation (G2: Rapamycin, G3: Mycophenolate mofetil and G4: Tacrolimus). RESULTS: Improved renal function and systemic inflammatory response were found among IS groups compared to the control group (Delta Urea p<0.0001; Delta Creatinine p<0.0001; Delta C3 p<0.001). The number of apoptotic nuclei in renal medulla in G1 was higher than in IS groups (p<0.0001). Tubular damage was less severe in IS groups respecting G1 (p<0.001). C3, TNF-alpha and IL-6 expression in kidney samples was reduced when IS was used compared to the control group. No differences were observed among the different immunosuppressive drugs tested. However, Heme oxygenase-1(HO 1) was increased only in Rapamycin treatment. CONCLUSIONS: These data suggest that the use of IS administered before transplant attenuates the IRI process after kidney transplantation in an animal model. PMID- 21034831 TI - Restricted expression of EBV encoded proteins in in vitro infected CLL cells. AB - CLL is not associated with EBV. CLL cells separated from blood express CR2, the complement receptor that serves also as EBV receptor. Thus CLL cells can be infected in vitro with the virus, however, in contrast to normal B lymphocytes, only rare CLL clones yield transformed lines. This is due to a restricted EBV encoded protein expression in the CLL cells, they express EBNAs, the virus encoded proteins that are localized in the nucleus, but not the cell membrane associated LMP-1, that is also pivotal for the virus induced transformation of B lymphocytes. This expression pattern seems to be unique to a defined B cell maturation window that is represented by the CLL cells. We named this restricted viral expression as Type IIb. Such B lymphocytes have been encountered in lymphoid tissues of infectious mononucleosis (IM) and in post transplant lymphoproliferative disease (PTLD). Moreover, they were shown in tissues of EBV infected "humanized" mice. The EBV encoded protein expression pattern may serve as a marker for the B cell differentiation stage from which CLL clones can develop. PMID- 21034832 TI - Toward understanding the mechanism of action of the yeast multidrug resistance transporter Pdr5p: a molecular modeling study. AB - Pleotropic drug resistant protein 5 (Pdr5p) is a plasma membrane ATP-binding cassette (ABC) transporter and the major drug efflux pump in Saccharomyces cerevisiae. The Pdr5p family of fungal transporters possesses a number of structural features significantly different from other modeled or crystallized ABC transporters, which include a reverse topology, an atypical ATP-binding site, a very low sequence similarity in the transmembrane section and long linkers between domains. These features present a considerable hurdle in molecular modeling studies of these important transporters. Here, we report the creation of an atomic model of Pdr5p based on a combination of homology modeling and ab initio methods, incorporating information from consensus transmembrane segment prediction, residue lipophilicity, and sequence entropy. Reported mutations in the transmembrane substrate-binding pocket that altered drug-resistance were used to validate the model, and one mutation that changed the communication pattern between transmembrane and nucleotide-binding domains was used in model improvement. The predictive power of the model was demonstrated experimentally by the increased sensitivity of yeast mutants to clotrimazole having alanine substitutions for Thr1213 and Gln1253, which are predicted to be in the substrate binding pocket, without reducing the amount of Pdr5p in the plasma membrane. The quality and reliability of our model are discussed in the context of various approaches used for modeling different parts of the structure. PMID- 21034833 TI - Wavelet-based fMRI analysis: 3-D denoising, signal separation, and validation metrics. AB - We present a novel integrated wavelet-domain based framework (w-ICA) for 3-D denoising functional magnetic resonance imaging (fMRI) data followed by source separation analysis using independent component analysis (ICA) in the wavelet domain. We propose the idea of a 3-D wavelet-based multi-directional denoising scheme where each volume in a 4-D fMRI data set is sub-sampled using the axial, sagittal and coronal geometries to obtain three different slice-by-slice representations of the same data. The filtered intensity value of an arbitrary voxel is computed as an expected value of the denoised wavelet coefficients corresponding to the three viewing geometries for each sub-band. This results in a robust set of denoised wavelet coefficients for each voxel. Given the de correlated nature of these denoised wavelet coefficients, it is possible to obtain more accurate source estimates using ICA in the wavelet domain. The contributions of this work can be realized as two modules: First, in the analysis module we combine a new 3-D wavelet denoising approach with signal separation properties of ICA in the wavelet domain. This step helps obtain an activation component that corresponds closely to the true underlying signal, which is maximally independent with respect to other components. Second, we propose and describe two novel shape metrics for post-ICA comparisons between activation regions obtained through different frameworks. We verified our method using simulated as well as real fMRI data and compared our results against the conventional scheme (Gaussian smoothing+spatial ICA: s-ICA). The results show significant improvements based on two important features: (1) preservation of shape of the activation region (shape metrics) and (2) receiver operating characteristic curves. It was observed that the proposed framework was able to preserve the actual activation shape in a consistent manner even for very high noise levels in addition to significant reduction in false positive voxels. PMID- 21034834 TI - Kinetic analysis in human brain of [11C](R)-rolipram, a positron emission tomographic radioligand to image phosphodiesterase 4: a retest study and use of an image-derived input function. AB - [(11)C](R)-rolipram provides a measure of the density of phosphodiesterase 4 (PDE4) in brain, an enzyme that metabolizes cAMP. The aims of this study were to perform kinetic modeling of [(11)C](R)-rolipram in healthy humans using an arterial input function and to replace this arterial input in humans with an image-derived input function. METHODS: Twelve humans had two injections of [(11)C](R)-rolipram. An image-derived input function was obtained from the carotid arteries and four blood samples. The samples were used for partial volume correction and for estimating the parent concentration using HPLC analysis. RESULTS: An unconstrained two-compartment model and Logan analysis measured distribution volume V(T), with good identifiability but with moderately high retest variability (15%). Similar results were obtained using the image input (ratio image/arterial V(T)=1.00+/-0.06). CONCLUSIONS: Binding of [(11)C](R) rolipram to PDE4 can be quantified in human brain using kinetic modeling and an arterial input function. Image input function from carotid arteries provides an equally accurate and reproducible method to quantify PDE4. PMID- 21034835 TI - From one to ten in a single stroke--resolving the European Eumidasanguinea (Phyllodocidae, Annelida) species complex. AB - We investigate the genetic structure of European lineages of the polychaete Eumida sanguinea with mitochondrial COI and nuclear ITS, and demonstrate the presence of ten cryptic species. Within the E. sanguinea species complex there are six different white pigmentation patterns but only three of these are unique for a single species. No other consistent morphological differences were observed. We give new species names to seven of the lineages from our study, providing examples of combined morphological and molecular diagnoses, apply the available name E. sanguinea to one species, and leave two lineages with single representatives unnamed. We also include new data and a diagnosis for the poorly known E. notata, which also belongs to the E. sanguinea species complex. PMID- 21034836 TI - Measurement of oxygen consumption by murine tissues in vitro. AB - INTRODUCTION: A novel in vitro system was developed to measure O2 consumption by murine tissues over several hours. METHODS: Tissue specimens (7-35 mg) excised from male Balb/c mice were immediately immersed in ice-cold Krebs-Henseleit buffer, saturated with 95% O2:5% CO2. The specimens were incubated at 37 degrees C in the buffer, continuously gassed with O2:CO2 (95:5). [O2] was determined as a function of time from the phosphorescence decay rates (1/tau) of Pd(II) meso tetra-(4-sulfonatophenyl)-tetrabenzoporphyrin. The values of 1/tau were linear with [O2]: 1/tau=1/tauo + kq [O2]; 1/tauo=the decay rate for zero O2, kq=the rate constant in s-1 MUM-1. RESULTS: NaCN inhibited O2 consumption, confirming oxidation occurred in the mitochondrial respiratory chain. The rate of respiration in lung specimens incubated in vitro for 3.9<=t<=12.4 h was 0.24+/ 0.03 MUM O2 min-1 mg-1 (mean+/-SD, n=28). The corresponding rate for the liver was 0.27+/-0.13 (n=11, t<=4.7 h), spleen 0.28+/- 0.07 (n=10, t<=5h), kidney 0.34+/-0.12 (n=7, t<=5h) and pancreas 0.35+/-0.09 (n=10, t<=4h). Normal tissue histology at hour 5 was confirmed by light and electron microscopy. There was negligible number of apoptotic cells by caspase 3 staining. DISCUSSION: This approach allows accurate assessment of tissue bioenergetics in vitro. PMID- 21034837 TI - In vivo measurement of the subchondral bone thickness of lumbar facet joint using magnetic resonance imaging. AB - OBJECTIVE: To measure in vivo thicknesses of the facet joint subchondral bone across genders, age groups, with or without low back pain symptom groups and spinal levels. METHODS: Lumbar (L1-L2 to L5-S1) magnetic resonance (MR) imaging was performed in 81 subjects (41 males and 40 females, mean age 37.6 years). Thicknesses of the subchondral bone were measured in 1620 facet joints using the MR images with custom-written image processing algorithms together with a multi threshold segmentation technique using each facet joint's middle axial-slice. This method was validated with 12 cadaver facet joints, scanned with both MR and micro-computed tomography images. RESULTS: An overall average thickness value for the 1620 analyzed joints was measured as 1.56+/-0.01 mm. The subchondral bone thickness values showed significant increases with successive lower spinal levels in the subjects without low back pain. The facet joint subchondral bone thickness in asymptomatic females was much smaller than in asymptomatic males. Mean subchondral bone thickness in the superior facet was greater than that in the inferior facet in both female and male asymptomatic subjects. CONCLUSIONS: This study is the first to quantitatively show subchondral bone thickness using a validated MR-based technique. The subchondral bone thickness was greater in asymptomatic males and increased with each successive lower spinal level. These findings may suggest that the subchondral bone thickness increases with loading. Furthermore, the superior facet subchondral bone was thicker than the inferior facet in all cases regardless of gender, age or spinal level in the subjects without low back pain. More research is needed to link subchondral bone microstructure to facet joint kinematics and spinal loads. PMID- 21034838 TI - The effect of hip and knee arthroplasty on oral anti-inflammatory use and the relationship to body mass index: results from the UK general practice research database. AB - OBJECTIVE: To determine the use of oral anti-inflammatory drugs in the year before and the 2 years after primary total hip (THR) or knee (TKR) replacement, and whether this varies according to Body mass Index (BMI). DESIGN: 28,068 THR's and 24,364 TKR's, with five matched controls per case were identified from the General Practitioner Research Database. Anti-inflammatory usage was categorized into "zero coverage" - no prescribed anti-inflammatory medication and ">80% coverage" - prescribed anti-inflammatory medication for greater than 80% of the days in the year. Secondary subset analysis was performed according to BMI. RESULTS: 1 year post-surgery the proportion of cases on >80% coverage reduced from 21% (95%confidence interval (CI): 20-22%) to 8% (95%CI: 7-10%) for THR and 21% (95%CI: 20-22%) to 13% (95%CI: 11-14%) for TKR, with no ongoing reduction at 2 years. Zero coverage increased at one and both time points. The proportion of THR's on >80% coverage increased with BMI pre-op. The magnitude in reduction post op was similar across all BMI groups. The proportion of TKR's on >80% coverage pre-op was greatest in extreme BMI categories. The magnitude in reduction post-op was similar across all BMI groups. CONCLUSION: THR/TKR's reduce the need for anti inflammatory medication with most benefit observed in the first post-operative year. Increasing BMI affects anti-inflammatory use both in the general population and those undergoing THR/TKR surgery but without strong evidence of a detrimental effect on the benefits of pain relief. PMID- 21034839 TI - Effects of joint effusion on proprioception in patients with knee osteoarthritis: a single-blind, randomized controlled clinical trial. AB - OBJECTIVE: To assess the effects of joint effusion on proprioceptive status in patients with knee osteoarthritis (OA). DESIGN: A single-blind, randomized, controlled clinical trial in 40 female subjects aged 50 years and over with painful knee OA. All subjects were randomly assigned to either the control or experimental group. A volume of 20 mL of normal saline was injected into the knee joint cavity of subjects in the experimental group under ultrasonographic guidance. Proprioceptive acuity was assessed by active repositioning of the lower limb using an electrogoniometer to measure knee joint position sense (JPS) under both non-weight-bearing (NWB) and weight-bearing (WB) conditions twice, with a 20 min rest interval. The experimental group performed the task twice (Test 1 and Test 2) before and within 5 min after joint infusion. The control group also performed Test 1 and Test 2 without joint infusion. The outcome of interest was the absolute angular error (AAE), ignoring the direction of the error, between the randomized target angle and the patient's reproduced angle of JPS values. RESULTS: Compared with the control group, JPS was significantly compromised in the experimental group in the NWB test after joint infusion (P=0.025). However, no significant differences in the angular error were observed between Test 1 and Test 2 in the control group for the NWB or WB test or in the experimental group for the WB test after infusion (P>0.05). CONCLUSIONS: This study showed that joint effusion impairs proprioceptive function in osteoarthritic knee joints. PMID- 21034840 TI - Diversity of Lactobacillus and Bifidobacterium in feces of herbivores, omnivores and carnivores. AB - The Lactobacillus and Bifidobacterium population in the feces of 26 animals (16 species) were studied by culture-dependent and culture-independent techniques. Lactobacilli were detected from a few herbivores, all carnivores and some omnivores. Lactobacillus johnsonii, Lactobacillus reuteri, Lactobacillus salivarius, Lactobacillus vaginalis and Lactobacillus ingluviei were the most dominant lactobacilli in carnivores. These species were, however, not predominant in herbivores and omnivores. Lactobacillus brevis, Lactobacillus casei, Lactobacillus parabuchneri, Lactobacillus plantarum, Lactobacillus sakei, Leuconostoc mesenteroides and Leuconostoc pseudomesenteroides, usually present in raw plant material, were present in omnivores but not in carnivores. Bifidobacteria were detected in only four herbivores and two omnivores. Bifidobacterium pseudolongum was the only Bifidobacterium species detected in herbivores. Bifidobacteria detected in the two omnivores are phylogenetically not closely related to known species and are possible novel species in the genus. PMID- 21034841 TI - Optimization of therapy for severe aplastic anemia based on clinical, biologic, and treatment response parameters: conclusions of an international working group on severe aplastic anemia convened by the Blood and Marrow Transplant Clinical Trials Network, March 2010. AB - Although recent advances in therapy offer the promise for improving survival in patients with severe aplastic anemia (SAA), the small size of the patient population, lack of a mechanism in North America for longitudinal follow-up of patients, and inadequate cooperation among hematologists, scientists, and transplant physicians remain obstacles to conducting large studies that would advance the field. To address this issue, the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) convened a group of international experts in March 2010 to define the most important questions in the basic science, immunosuppressive therapy (IST), and bone marrow transplantation (BMT) of SAA and propose initiatives to facilitate clinical and biologic research. Key conclusions of the working group were: (1) new patients should obtain accurate, expert diagnosis and early identification of biologic risk; (2) a population-based SAA outcomes registry should be established in North America to collect data on patients longitudinally from diagnosis through and after treatment; (3) a repository of biologic samples linked to the clinical data in the outcomes registry should be developed; (4) innovative approaches to unrelated donor BMT that decrease graft-versus-host disease are needed; and (5) alternative donor transplantation approaches for patients lacking HLA-matched unrelated donors must be improved. A partnership of BMT, IST, and basic science researchers will develop initiatives and partner with advocacy and funding organizations to address these challenges. Collaboration with similar study groups in Europe and Asia will be pursued. PMID- 21034843 TI - Functional analyses of lissencephaly-related proteins in Dictyostelium. AB - Lissencephaly is a severe brain developmental disease in human infants, which is usually caused by mutations in either of two genes, LIS1 and DCX. These genes encode proteins interacting with both the microtubule and the actin systems. Here, we review the implications of data on Dictyostelium LIS1 for the elucidation of LIS1 function in higher cells and emphasize the role of LIS1 and nuclear envelope proteins in nuclear positioning, which is also important for coordinated cell migration during neocortical development. Furthermore, for the first time we characterize Dictyostelium DCX, the only bona fide orthologue of human DCX outside the animal kingdom. We show that DCX functionally interacts with LIS1 and that both proteins have a cytoskeleton-independent function in chemotactic signaling during development. Dictyostelium LIS1 is also required for proper attachment of the centrosome to the nucleus and, thus, nuclear positioning, where the association of these two organelles has turned out to be crucial. It involves not only dynein and dynein-associated proteins such as LIS1 but also SUN proteins of the nuclear envelope. Analyses of Dictyostelium SUN1 mutants have underscored the importance of these proteins for the linkage of centrosomes and nuclei and for the maintenance of chromatin integrity. Taken together, we show that Dictyostelium amoebae, which provide a well-established model to study the basic aspects of chemotaxis, cell migration and development, are well suited for the investigation of the molecular and cell biological basis of developmental diseases such as lissencephaly. PMID- 21034842 TI - Comparison of outcomes after transplantation of G-CSF-stimulated bone marrow grafts versus bone marrow or peripheral blood grafts from HLA-matched sibling donors for patients with severe aplastic anemia. AB - We compared outcomes of patients with severe aplastic anemia (SAA) who received granulocyte-colony stimulating factor (G-CSF)-stimulated bone marrow (G-BM) (n = 78), unstimulated bone marrow (BM) (n = 547), or peripheral blood progenitor cells (PBPC) (n = 134) from an HLA-matched sibling. Transplantations occurred in 1997 to 2003. Rates of neutrophil and platelet recovery were not different among the 3 treatment groups. Grade 2-4 acute graft-versus-host disease (aGVHD) (relative risk [RR] = 0.82, P = .539), grade 3-4 aGVHD (RR = 0.74, P = .535), and chronic GVHD (cGVHD) (RR = 1.56, P = .229) were similar after G-BM and BM transplants. Grade 2-4 aGVHD (RR = 2.37, P = .012) but not grade 3-4 aGVHD (RR = 1.66, P = .323) and cGVHD (RR = 5.09, P < .001) were higher after PBPC transplants compared to G-BM. Grade 2-4 (RR = 2.90, P < .001), grade 3-4 (RR = 2.24, P = .009) aGVHD and cGVHD (RR = 3.26, P < .001) were higher after PBPC transplants compared to BM. Mortality risks were lower after transplantation of BM compared to G-BM (RR = 0.63, P = .05). These data suggest no advantage to using G-BM and the observed higher rates of aGVHD and cGVHD in PBPC recipients warrants cautious use of this graft source for SAA. Taken together, BM is the preferred graft for HLA-matched sibling transplants for SAA. PMID- 21034844 TI - Pertussis-induced cough. AB - Pertussis (whooping cough) is one of the commonest vaccine preventable diseases in the UK, despite vaccination coverage being maintained for the last 15 years at over 90% among infants and the addition of a pre-school booster to the UK national immunisation programme in 2001. However, it is known that pertussis vaccine does not confer long-term immunity to clinical infection. Evidence of pertussis infection has been reported in 37% of children presenting in UK primary care and 20% of adolescents and adults presenting in Canadian health centres with persistent cough. In children and adults with persistent cough, paroxysmal coughing is the most sensitive indicator of pertussis, but has poor specificity and limited diagnostic value. Vomiting and whooping, particularly in combination, are stronger predictors of pertussis. Cough duration is longer in children than in adults with pertussis (median cough duration 112 days versus 42 days); individuals may take even longer to recover fully and regain previous levels of exercise tolerance. A diagnosis of pertussis may be confirmed by culture, Polymerase Chain Reaction (PCR) or serology. Single estimates of anti-pertussis toxin (PT) antibody titres in blood or oral fluid samples are highly specific. There are currently no proven efficacious treatments for pertussis-induced cough. Treatment with macrolide antibiotics reduces the duration of an individual's infectious period, but does not alter the duration of cough. Further research is needed to re-examine the epidemiology of pertussis in countries with different vaccination schedules, find efficacious treatments and develop methods of measuring cough frequency and severity in patients with pertussis-induced cough. PMID- 21034845 TI - The Syk/CARD9-coupled receptor Dectin-1 is not required for host resistance to Mycobacterium tuberculosis in mice. AB - There is interest in identifying the pattern recognition receptors involved in initiating protective or non-protective host responses to Mycobacterium tuberculosis (Mtb). Here we explored the role of the Syk/CARD9-coupled receptor, Dectin-1, using an aerosol model of Mtb infection in wild-type and Dectin-1 deficient mice. We observed a reduction in pulmonary bacilli burdens in the Dectin-1 deficient animals, but this did not correlate with significant changes in pulmonary pathology, cytokine levels or ability of these animals to survive the infection. Thus Dectin-1 makes a minor contribution to susceptibility to Mtb infections in mice. PMID- 21034846 TI - Cell-mediated immunity in human brucellosis. AB - Brucella can parasitize within human antigen-presenting cells modifying phagocytosis, phagolysosome fusion, antigen presentation, cytokine secretion, and apoptosis. Subversion of innate immune mechanisms by Brucella leads to defective Th1 immune responses and T-cell anergy in chronic brucellosis patients. This review summarizes the cellular immune responses in brucellosis, based on data derived exclusively from human cells or cell lines. PMID- 21034847 TI - Dephosphorylation of West Nile virus capsid protein enhances the processes of nucleocapsid assembly. AB - West Nile virus (WNV) capsid (C) protein is one of the three viral structural proteins and it encapsidates the viral RNA to form the nucleocapsid. It is known to be a multifunctional protein involved in assembly and apoptosis. WNV C protein was previously found to be phosphorylated in infected cells and bioinformatic analysis revealed 5 putative phosphorylation sites at serine 26, 36, 83, 99 and threonine 100. Phosphorylation was abolished through mutagenesis of these putative phosphorylation sites to investigate how phosphorylation could affect the processes of nucleocapsid assembly like RNA binding, oligomerization and cellular localization. It was found that phosphorylation attenuated its RNA binding activity. Although oligomerization was not inhibited by mutagenesis of the putative phosphorylation sites, the rate of dimerization and oligomerization was affected. Hypophosphorylation of C protein reduced its nuclear localization efficiency and hence enhanced cytoplasmic localization. This study also revealed that although WNV C is phosphorylated in infected cells, the relative level of phosphorylation is reduced over the course of an infection to promote RNA binding and nucleocapsid formation in the cytoplasm. This is the first report to describe how dynamic phosphorylation of WNV C protein modulates the processes involved in nucleocapsid assembly. PMID- 21034848 TI - EXO70 protein influences dengue virus secretion. AB - The involvement of host proteins in assisting the exocytosis of flaviviruses is largely unknown. In this study, we aimed to investigate if dengue virus (DENV) utilizes the exocyst components to aid the exocytosis of virus particles. This study identified that EXO70 protein, a member of the exocyst complex influenced DENV infection. Dengue virus production was significantly attenuated in EXO70 knock-down cells. EXO70 did not influence viral transcription and translation. It influenced virus egression/secretion from DENV-infected cells. We also showed that EXO70 expression was up-regulated from 18 h post-infection following DENV infection. Although the envelope protein of DENV influenced EXO70 expression, the co-expression of pre-membrane and envelope proteins significantly increased the expression levels of EXO70 during DENV infection. When pre-membrane protein was expressed alone, there was no significant difference in the expression levels of EXO70. This indicated that the presence of pre-membrane protein might help in the proper folding of envelope protein. Increased expression levels of EXO70 might help in the exocytosis process of virus or subviral particles. PMID- 21034849 TI - Spontaneous secretion of interleukin-17 and -22 by human cervical cells in Chlamydia trachomatis infection. AB - To investigate whether IL-17A (IL-17) and IL-22 are produced in response to Chlamydia trachomatis infection, the cervical washes of 27 women with C. trachomatis infection and 17 C. trachomatis negative controls were collected. The levels of cytokines were determined in the cervical wash and in the supernatant of cervical and systemic cell cultures upon C. trachomatis antigen stimulation. C. trachomatis infection appeared to activate local IL-17 and IL-22 production more efficiently than IFN-gamma production. In the cervical wash of infected women, median concentrations of IL-17 and -22 were 5- and 3-fold higher, respectively, than in negative controls. The spontaneous intracellular expression of these cytokines was analysed by flow cytometry in blood and cervical cells and 26% of cervical mononuclear cells from infected women were shown to produce IL-22 and 12% to coproduce IL-17 and IL-22. In addition, it was demonstrated that 20 25% of IL-22 producing and IL-17-IL-22 coproducing cervical CD4+ T cells expressed the mucosal homing receptor CCR6. These results suggest that CCR6 is involved in the migration of these cells to the cervix and that IL-17 and IL-22 might play a role in the immune response at the site of C. trachomatis infection. PMID- 21034850 TI - The ADP-ribosylation factor 1 (Arf1) is involved in regulating copper uptake. AB - Copper is a cofactor for many essential enzymes in aerobic organisms. When intracellular copper levels are elevated, the Menkes (ATP7A) P-Type ATPase traffics from the trans-Golgi network (TGN) towards the plasma membrane to facilitate copper efflux. The ADP-ribosylation factor 1 (Arf1) is required for maintenance of Golgi architecture and for vesicular trafficking, including the copper-responsive trafficking of ATP7A. Here we report an ATP7A-independent role of Arf1 in copper homeostasis. Whilst the loss of ATP7A function increased copper levels, RNA interference mediated Arf1 knockdown reduced copper accumulation in HeLa cells as well as in both wild-type and ATP7A-null cultured fibroblasts. Arf1 therefore affected copper levels independently of ATP7A mediated copper efflux. Knockdown of Arf79F, the Drosophila melanogasterArf1 orthologue, also reduced copper accumulation in cultured Drosophila S2 cells, indicating an evolutionarily conserved role for this protein in cellular copper homeostasis. Whereas severe Arf1 inhibition with brefeldin A caused fragmentation and dispersal of the TGN resident protein Golgin 97, the peri-nuclear localisation of the Golgin 97 was retained following Arf1 knockdown, consistent with a moderate reduction in Arf1 activity. Ctr1 levels at the plasma membrane of cultured fibroblast cells were reduced following Arf1 knockdown, indicating an Arf1-dependent trafficking pathway is required for correct distribution of this copper uptake protein. Arf1 dependent trafficking pathways are therefore required for optimal copper uptake efficiency in cultured human and Drosophila cells. PMID- 21034851 TI - Evolution of patterning mechanisms. PMID- 21034852 TI - The mouthparts of Scutigerella immaculata: Correspondences and variation among serially homologous head appendages. AB - Descriptions of the skeletomuscular system of the symphylan head are characterized by a high number of incongruencies among authors. The increased accuracy and transparency of 3D-reconstruction methods allows for an allocation of some of the incongruencies to (i) misinterpretations of literature descriptions, or (ii) different views of what constitutes a separate muscle. A structural comparison allows to homologize muscles among the serially arranged mouthparts of Symphyla. PMID- 21034853 TI - Novel intravascular defibrillator: defibrillation thresholds of intravascular cardioverter-defibrillator compared to conventional implantable cardioverter defibrillator in a canine model. AB - BACKGROUND: An intravascular, percutaneously placed implantable defibrillator (InnerPulse percutaneous intravascular cardioverter-defibrillator [PICD]) with a right ventricular (RV) single-coil lead and titanium electrodes in the superior vena cava (SVC) and the inferior vena cava (IVC) has been developed. OBJECTIVE: The purpose of this study was to compare defibrillation thresholds (DFTs) of the PICD to those of a conventional implantable cardioverter-defibrillator (ICD) in canines. METHODS: Eight Bluetick hounds were randomized to initial placement of either a PICD or a conventional ICD. For PICD DFTs, a single-coil RV defibrillator lead was placed in the RV apex, and the device was positioned in the venous vasculature with electrodes in the SVC and IVC. With the conventional ICD, an RV lead was placed in the RV apex and an SVC coil was appropriately positioned. The ICD active can (AC) was implanted in a subcutaneous pocket formed in the left anterior chest wall and connected to the lead system. DFT was determined by a three-reversal, step up-down method to estimate the 80% success level. Two configurations were tested for the conventional ICD (#1: RV to SVC+AC; #2: RV to AC). A single configuration (RV to SVC+IVC) was evaluated for the PICD. RESULTS: Mean PICD DFT was 14.8 +/- 1.53 (SE) J. Conventional #1 configuration demonstrated mean DFT of 20.2 +/- 2.45 J and #2 of 27.5 +/- 1.95 J. The PICD had a significantly lower DFT than the better conventional ICD configuration (#1; mean difference 5.4 +/- 2.1 J, P <.05, paired t-test, N = 8). CONCLUSION: The new intravascular defibrillator had a significantly lower DFT than the conventional ICD in this canine model. PMID- 21034854 TI - Real-time magnetic resonance imaging-guided radiofrequency atrial ablation and visualization of lesion formation at 3 Tesla. AB - BACKGROUND: Magnetic resonance imaging (MRI) allows visualization of location and extent of radiofrequency (RF) ablation lesion, myocardial scar formation, and real-time (RT) assessment of lesion formation. In this study, we report a novel 3 Tesla RT -RI based porcine RF ablation model and visualization of lesion formation in the atrium during RF energy delivery. OBJECTIVE: The purpose of this study was to develop a 3-Tesla RT MRI-based catheter ablation and lesion visualization system. METHODS: RF energy was delivered to six pigs under RT MRI guidance. A novel MRI-compatible mapping and ablation catheter was used. Under RT MRI, this catheter was safely guided and positioned within either the left or right atrium. Unipolar and bipolar electrograms were recorded. The catheter tip tissue interface was visualized with a T1-weighted gradient echo sequence. RF energy was then delivered in a power-controlled fashion. Myocardial changes and lesion formation were visualized with a T2-weighted (T2W) half Fourier acquisition with single-shot turbo spin echo (HASTE) sequence during ablation. RESULTS: RT visualization of lesion formation was achieved in 30% of the ablations performed. In the other cases, either the lesion was formed outside the imaged region (25%) or the lesion was not created (45%) presumably due to poor tissue-catheter tip contact. The presence of lesions was confirmed by late gadolinium enhancement MRI and macroscopic tissue examination. CONCLUSION: MRI compatible catheters can be navigated and RF energy safely delivered under 3 Tesla RT MRI guidance. Recording electrograms during RT imaging also is feasible. RT visualization of lesion as it forms during RF energy delivery is possible and was demonstrated using T2W HASTE imaging. PMID- 21034856 TI - Pioglitazone attenuates inflammatory atrial fibrosis and vulnerability to atrial fibrillation induced by pressure overload in rats. AB - BACKGROUND: Inflammatory processes are involved in the pathogenesis of atrial fibrillation (AF). OBJECTIVE: The purpose of this study was to test the hypothesis that atrial fibrosis and enhanced vulnerability to AF evoked by pressure overload can be attenuated by pioglitazone, a peroxisome proliferator activated receptor-gamma agonist, via suppression of inflammatory profibrotic signals. METHODS: Male Sprague-Dawley rats were subjected to abdominal aortic constriction (AAC). Pioglitazone 3 mg/kg/day or vehicle was orally administered for 4 weeks. RESULTS: Western blot analysis revealed that AAC enhanced expression of monocyte chemoattractant protein (MCP)-1, transforming growth factor-beta1 and alpha-smooth muscle actin in the left atrium (LA), which was suppressed by pioglitazone. Messenger RNA expression of collagen type 1 and atrial natriuretic peptide in the LA was increased by AAC, which was suppressed by pioglitazone. Gelatin zymography demonstrated that activity of matrix metalloproteinase-9 was increased by AAC, which was suppressed by pioglitazone. Pioglitazone attenuated AAC-induced LA fibrosis. In isolated-perfused heart experiments, AAC did not alter the refractory period of the LA or the right atrium (RA), but it did prolong the interatrial conduction time. Programmed extrastimuli from the RA induced AF in all of the AAC-treated rats (8/8 [100%]). This was suppressed by pioglitazone (2/8 [25%], P <.05) with normalization to interatrial conduction time. CONCLUSION: The results of this study suggest that inflammatory profibrotic mechanisms are involved in this pressure-overloaded AF model. The results also suggest that pioglitazone is effective at attenuating atrial fibrosis, possibly via suppression of MCP-1-mediated inflammatory profibrotic processes. PMID- 21034857 TI - To the editor--ICD implantation early after myocardial infarction. PMID- 21034858 TI - Left atrial pressure and dominant frequency of atrial fibrillation in humans. AB - BACKGROUND: Atrial stretch is thought to play a role in the development of atrial fibrillation (AF). However, the precise mechanism by which stretch contributes to AF maintenance in humans is unknown. OBJECTIVE: The purpose of this study was to determine the impact of left atrial (LA) pressure on AF frequency in patients undergoing catheter ablation of AF. METHODS: The subjects of this study were 58 consecutive patients with persistent AF (n = 40) or paroxysmal AF (n = 18) undergoing LA ablation. LA pressure was measured before ablation. Both atria and the coronary sinus were mapped, and regional dominant frequency (DF) was determined. RESULTS: Mean LA pressure in the persistent AF group was significantly higher than in the paroxysmal AF group (18 +/- 5 vs 10 +/- 4 mmHg, P <.0001). Mean DF in the persistent AF group was also higher than in the paroxysmal AF group (6.36 +/- 0.51 Hz and 5.83 +/- 0.54 Hz, P = .0006). In patients with persistent AF, there was a significant correlation between LA pressure and DF at the LA appendage (r = 0.55, P = .0002). DF(max) was found at the LA appendage region in 24 (60%) of the 40 patients with persistent AF (P = .0006). In multivariate analysis, LA pressure was the only independent predictor of DF(max) in the LA appendage (P = .04, odds ratio 1.41, 95% confidence interval 1.02-1.94). CONCLUSION: Higher LA pressure in patients with persistent AF implies that these patients are more vulnerable to stretch-related remodeling than are patients with paroxysmal AF. The DF of AF was directly related to LA pressure in patients with persistent AF. This finding suggests that atrial stretch may contribute to the maintenance of AF in humans by stabilizing high-frequency sources. PMID- 21034859 TI - Multicompartment vectors as novel drug delivery systems: selective activation of Tgammadelta lymphocytes after zoledronic acid delivery. AB - Multicompartment nanoscopic carriers can be easily assembled by inducing the aggregation of anionic "hybrid" niosomes by means of cationic biocompatible polyelectrolytes. The resulting vesicle clusters, whose size and overall net charge can be easily controlled by varying the polyelectrolyte-to-particle charge ratio, show an interesting potential for multidrug delivery. In this article we provide strong evidence for their effective use in vitro as multicompartment vectors selectively directed toward monocyte/macrophage cells, showing that the monocyte/macrophage-mediated activation of Tgammadelta lymphocytes induced by zoledronic acid is enhanced by a factor 10(3) when the zoledronic acid is intracellularly delivered through these carriers. Furthermore, the multicompartment E-polylysine niosome clusters, with their intrinsic selectivity toward macrophages, appear particularly suitable for implementing therapeutic strategies against chronically infected macrophages. FROM THE CLINICAL EDITOR: E polylysine niosome clusters, with their intrinsic selectivity toward macrophages, offer the potential for multidrug delivery. The effectiveness of aminobisphosphonate zoledronate is demonstrated to enhance the recruitment of Tgammadelta lymphocytes by macrophages by 2 orders of magnitude, suggesting a new therapeutic strategy for addressing pathologies featuring chronically infected macrophages. PMID- 21034860 TI - Self-adjuvanting polyacrylic nanoparticulate delivery system for group A streptococcus (GAS) vaccine. AB - Infection with Streptococcus pyogenes, commonly known as group A Streptococcus (GAS), is responsible for acute and postinfectious complications, including rheumatic fever and rheumatic heart disease (RHD). RHD is a global health burden, and Australia's indigenous population has one of the highest incidences of RHD worldwide. A potential peptide (J14) vaccine candidate has been previously identified from the C-terminal region of the M protein. However, such peptide based vaccine development is hampered by a lack of carriers and adjuvants suitable for humans use. We have developed a fully synthetic peptide subunit vaccine candidate based on polyacrylate dendritic polymer. Intranasal administration of this nanoparticulate construct without additional adjuvant induced J14-specific IgG, which was also capable of in vitro opsonization of GAS, highlighting the potential of self-adjuvanting polyacrylate nanoparticle-based construct as a peptide vaccine delivery platform that may afford promising opportunities for treating systemic GAS infection. FROM THE CLINICAL EDITOR: Polyacrylate dendrimers offer a unique approach to a nasally administered vaccine for addressing rheumatic heart disease. This paper describes the delivery of the J14 peptide, a C-terminal derivative of M-protein in group A Streptococcus. PMID- 21034861 TI - Selective toxicity of ZnO nanoparticles toward Gram-positive bacteria and cancer cells by apoptosis through lipid peroxidation. AB - Nanoparticles are increasingly recognized for their utility in biological applications including nanomedicine. The present study investigated the toxicity of zinc oxide (ZnO) nanoparticles toward prokaryotic and eukaryotic cells. Cytotoxicity of ZnO to mammalian cells was studied using human myeloblastic leukemia cells (HL60) and normal peripheral blood mononuclear cells (PBMCs). Antibacterial activity of ZnO was also tested against the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, as well as the Gram-positive bacterium Staphylococcus aureus, and the effect was more pronounced with the Gram positive than the Gram-negative bacteria. ZnO nanoparticles exhibited a preferential ability to kill cancerous HL60 cells as compared with normal PBMCs. The nanoparticles enhanced ultrasound-induced lipid peroxidation in the liposomal membrane. The work suggested two mechanisms underlying the toxicity of ZnO: (i) involvement of the generation of reactive oxygen species (ROS) and (ii) induction of apoptosis. The work also revealed potential utility of ZnO nanoparticles in the treatment of cancer, for their selective toxicity to cancer cells. FROM THE CLINICAL EDITOR: The toxicity of zinc oxide to bacteria was related to the generation of reactive oxygen species and to the induction of apoptosis. Interestingly, these effects were differentially greater in human myeloblastic leukemia cells (HL60) than normal peripheral blood mononuclear cells. PMID- 21034862 TI - Bronchoconstriction during alveolar hypocapnia and systemic hypercapnia in dogs with a cardiopulmonary bypass. AB - The roles of the alveolar and systemic CO2 on the lung mechanics were investigated in dogs subjected to cardiopulmonary bypass. Low-frequency pulmonary impedance data (Z(L)) were collected in open-chest dogs with an alveolar CO2 level (FA(CO2)) of 0.2-7% and during systemic hypercapnia before and after elimination of the vagal tone. Airway resistance (R(aw)), inertance (I(aw)), parenchymal damping (G) and elastance (H) were estimated from the Z(L). The highest R(aw) observed at 0.2% FA(CO2),which decreased markedly up to a FA(CO2) of 2% (212 +/- 24%), and remained unchanged under normo- and hypercapnia (FA(CO2) 2-7%). These changes were associated with smaller decreases in I(aw) (-16.6 +/- 3.7%), mild elevations in G (25.7 +/- 4.7%), and no change in H. Significant increases in all mechanical parameters were observed following systemic hypercapnia; atropine counteracted the R(aw) rises. We conclude that severe alveolar hypocapnia may contribute to minimization of the ventilation-perfusion mismatch by constricting the airways in poorly perfused lung regions. The constrictor potential of systemic hypercapnia is mediated by vagal reflexes. PMID- 21034863 TI - Bone nodules on chitosan-polygalacturonic acid-hydroxyapatite nanocomposite films mimic hierarchy of natural bone. AB - The ultimate goal of bone tissue engineering is to develop bony tissues on tissue engineered constructs that mimic the native bone. Nanoscale characterization of in vitro generated bony tissues on engineered scaffolds is essential to understanding both the physical and mechanical characteristics of the engineered bone. Bone nodule formation, a typical early indicator of bone formation was observed on chitosan-polygalacturonic acid-hydroxyapatite (Chi-PgA-HAP) nanocomposite films without the use of differentiating media. Thus, the Chi-PgA HAP substrates designed are osteoinductive and provide an appropriate microenvironment for cell organization and tissue regeneration. Imaging using atomic force microscopy revealed several levels of hierarchical structures of bone in the bone nodules, consisting of mineralized collagen fibers, fibrils and mineral deposits in extrafibrillar spaces. The nanoscale elastic properties of the collagen and mineral crystals were found to be in close agreement with the experimental and simulations results on natural bone reported in the literature. Fourier transform infrared spectroscopy experiments indicate the presence of collagen and biological apatite in bone nodules exhibiting the characteristics of newly precipitated, immature bone. Collectively, our structural, chemical, and mechanical analyses support the conclusion that synthetic bone nodules mimic the hierarchy of natural bone. PMID- 21034864 TI - Six novel ATP7B mutations in Thai patients with Wilson disease. AB - WD is an autosomal recessive disorder of copper transport resulting in excessive copper deposition in the liver and brain. It is caused by defects of ATP7B encoding a copper transporting P-type ATPase. To identify the mutations in ATP7B in Thai patients with WD, DHPLC analysis was applied to detect mutations and polymorphisms of the entire ATP7B gene in 19 Thai patients with WD. Mutations in ATP7B were identified in 14 of 19 patients: 2 homozygotes, 8 compound heterozygotes and 4 heterozygotes. Eighteen mutations distributed throughout the entire coding region of ATP7B gene including 11 missense, 3 nonsense, 1 splice site, 1 deletion and 2 insertions. Of 18 different mutations identified, 6 were found to be novel. Twelve single nucleotide polymorphisms (SNPs) were also identified and two SNPs have not yet previously been reported. Segregation analysis using DHPLC analysis showed mutation transmission patterns within each family of Thai patients with WD. Mutations in ATP7B in Thai patients with WD are worth adding into the public database for genetic epidemiology and population genetics. PMID- 21034865 TI - In vitro modulation of LPS/calcimycin induced inflammatory and allergic mediators by pure compounds of Andrographis paniculata (King of bitters) extract. AB - The aim of the current study is to probe the anti-inflammatory/anti-allergic potential of seven phytoconstituents (andrographolide, neoandrographolide, isoandrographolide, andrograpanin, 14-deoxy-11,12-didehydroandrographolide, 7-O methylwogonin and skullcapflavone-I) isolated from Andrographis paniculata (King of bitters) on the production of key inflammatory/allergic mediators (NO, PGE(2), IL-1 beta, IL-6, LTB(4), TXB(2) and histamine). The results demonstrated that andrographolide, isoandrographolide, 7-O-methylwogonin and skullcapflavone-I significantly inhibited LPS stimulated NO and PGE(2) release in J774A.1 macrophages. Andrographolide, isoandrographolide and 7-O-methylwogonin showed considerable inhibition of IL-1 beta production in LPS elicited macrophages. LPS induced IL-6 production was significantly inhibited by andrographolide, isoandrographolide and skullcapflavone-I in a concentration dependent manner. The results revealed that andrographolide, isoandrographolide and skullcapflavone-I significantly decreased TXB(2) release in A23187 activated HL-60 promyelocytic cells. Furthermore, the anti-allergic properties of the phytoconstituents was investigated on A23187 induced LTB(4) production (HL-60 cells) and histamine release (RBL-2H3 basophilic cells). The results showed that only skullcapflavone I and 7-O-methylwogonin showed marked inhibitory effect on LTB(4) production, however, only 7-O-methylwogonin exerted dose-dependent inhibition towards histamine release. Therefore, this study indicates that some of these phytoconstituents exhibit potent anti-inflammatory/anti-allergic effects by modulating different inflammatory/allergic mediators. Hence, these phytoconstituents might provide useful phytomedical treatment against variety of inflammatory and allergic disorders. PMID- 21034867 TI - Advocacy is a natural part of our life and work. PMID- 21034868 TI - A decade of work coming together: nutrition care, electronic health records, and the HITECH Act. PMID- 21034869 TI - Stage 1 of "meaningful use" of electronic health records released: what it means for RDs and DTRs. PMID- 21034870 TI - Making wellness delicious: building a healthier Chicago's FIT City program. PMID- 21034871 TI - Home economics makes a comeback: opportunities for RDs to become part of the curriculum. PMID- 21034873 TI - Grassroots efforts behind restaurant menu labeling legislation. PMID- 21034874 TI - Design, development, and achievements of a youth-led nutrition and physical activity intervention in a Pacific community in New Zealand. PMID- 21034875 TI - Development of the 2010 US Dietary Guidelines Advisory Committee Report: perspectives from a registered dietitian. PMID- 21034876 TI - Examining the role of nutrition support and outcomes for hospitalized patients: putting nutrition back in the study design. PMID- 21034877 TI - n-3 fatty acid intake and periodontal disease. PMID- 21034878 TI - The influence of a behavioral weight management program on disordered eating attitudes and behaviors in children with overweight. AB - BACKGROUND: Behavioral interventions targeting children with overweight have been successful in facilitating weight loss; however, there is concern that these programs produce disordered eating attitudes among youth. OBJECTIVE: The purpose of this research was to determine whether youth with overweight receiving one of two behavioral interventions were more likely to report an increase in disordered eating attitudes over time compared to a waitlist control and to determine psychosocial predictors of eating-disordered attitudes at 6-month follow-up. DESIGN: Participants were randomized to one of two behavioral lifestyle interventions or a waitlist control. Data were collected at baseline, post treatment, and 6-month follow-up. PARTICIPANTS/SETTING: Participants were 68 youths with overweight, aged 8 to 13 years, and their parent(s) who lived in rural north central Florida. The project ran from January 2006 to January 2008. INTERVENTION: Each treatment condition consisted of 12 group sessions over 16 weeks. MAIN OUTCOME MEASURES: Parents completed a demographic form and the Child Feeding Questionnaire. Children completed the Children's Eating Attitudes Test, Schwartz Peer Victimization Scale, and Children's Body Image Scale. STATISTICAL ANALYSES PERFORMED: Mixed 2*2 analyses of variance were used to examine the effect of treatment on eating attitudes. Hierarchical linear regression was used to assess whether baseline levels of psychosocial variables predicted disordered eating attitudes at follow-up, controlling for baseline eating attitudes and treatment condition. RESULTS: Youth who participated in the behavioral interventions did not report significant increases in disordered eating attitudes over time compared to the waitlist control. Across all conditions, higher levels of body dissatisfaction, peer victimization, parent restrictive feeding practices, and concern for child weight at baseline predicted higher levels of disordered eating attitudes at follow-up. CONCLUSIONS: These findings do not provide evidence that behavioral interventions lead to an increase in unhealthy eating attitudes and behaviors. Future research should examine the effects of incorporating eating disorder prevention in pediatric weight management programs. PMID- 21034879 TI - Dietary intake of vitamin B-6, plasma pyridoxal 5'-phosphate, and homocysteine in Puerto Rican adults. AB - BACKGROUND: Vitamin B-6 is an important cofactor in many metabolic processes. However, vitamin B-6 intake and plasma status have not been well studied in the Puerto Rican population, a group with documented health disparities. OBJECTIVE: To assess dietary intake of vitamin B-6, food sources, and plasma status of pyridoxal 5'-phosphate (PLP), and their associations with plasma homocysteine in 1,236 Puerto Rican adults, aged 45 to 75 years, living in the greater Boston area. DESIGN: Baseline data were analyzed cross-sectionally. METHOD: Questionnaire data were collected by home interview. Dietary intake was assessed with a semiquantitative food frequency questionnaire. Plasma PLP and homocysteine were assayed from blood samples collected in the home. RESULTS: The mean daily intake of vitamin B-6 was 2.90 +/- 1.28 mg for men and 2.61 +/- 1.29 mg for women (P<0.001). Approximately 11% were deficient (PLP <4.94 ng/mL [PLP <20 nmol/L]) and another 17% insufficient (PLP >= 4.94 but <7.41 ng/mL [PLP >= 20 but <30 nmol/L]). Household income below the poverty threshold, physical inactivity, and current smoking were significantly associated with lower plasma PLP (P<0.05). Food groups contributing most to vitamin B-6 intake included ready-to-eat cereals, poultry, rice, potatoes, and dried beans. However, only intake of ready to-eat cereals and use of supplements with vitamin B-6 were significantly associated with plasma PLP sufficiency (>= 7.41 vs <7.41 ng/mL [PLP >= 30 vs <30 nmol/L], P<0.01). Both vitamin B-6 intake and PLP were significantly associated with plasma total homocysteine (P<0.001). The association between PLP and homocysteine remained statistically significant after further adjustment for plasma vitamin B-12 and folate (P=0.028). CONCLUSIONS: Given the known importance of vitamin B-6 to health, the high prevalence of low vitamin B-6 status in this Puerto Rican population is of concern. Further work is needed to clarify the potential role that insufficient vitamin B-6 may have in relation to the observed health disparities in this population. PMID- 21034880 TI - n-3 fatty acids and periodontitis in US adults. AB - BACKGROUND: Periodontitis is a common, chronic inflammatory disease. Although n-3 fatty acids have anti-inflammatory properties, it is unclear whether n-3 fatty acids can treat or prevent periodontitis. METHOD: We studied 9,182 adults aged 20 years and older who participated in the National Health and Nutrition Examination Survey between 1999 and 2004. Periodontitis was assessed by dental exam and was defined as >4 mm pocket depth and >3 mm attachment loss in any one tooth. Intake of n-3 fatty acids was assessed by 24-hour dietary recall. We used multivariable logistic regression to estimate the associations between periodontitis and intakes of docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and linolenic acid (LNA). RESULTS: The weighted prevalence and 95% confidence interval (CI) of periodontitis was 8.2% (95% CI 7.0 to 9.4). Compared with the lowest tertiles, the adjusted odds ratios for periodontitis associated with the highest tertiles of dietary n-3 intake were 0.78 (95% CI 0.61 to 1.00; P=0.009) for DHA, 0.85 (95% CI 0.67 to 1.08; P=0.10) for EPA, and 0.86 (95% CI 0.60 to 1.23; P=0.28) for LNA. The associations were little changed by multivariable adjustment or exclusion of individuals reporting use of dietary supplements containing DHA, EPA, or LNA. CONCLUSIONS: In this nationally representative sample, higher dietary intakes of DHA and, to a lesser degree, EPA, were associated with lower prevalence of periodontitis. Interventional studies are needed to confirm the potential protective effects of n-3 fatty acids on periodontitis. PMID- 21034881 TI - The meaning of food and eating among home parenteral nutrition-dependent adults with intestinal failure: a qualitative inquiry. AB - Using content and interpretative phenomenological analysis, we explored the meaning of food and eating from the perspective of adults receiving home parenteral nutrition (PN). The aim of this research was to obtain a deeper understanding of how issues related to food and eating influence quality of life (QOL). Semistructured telephone interviews were conducted between May 2006 and January 2007 with 24 adults with intestinal failure and home PN dependency. The analysis revealed themes relevant to eating behaviors, hunger and thirst, strategies for dining in restaurants, and a perception of wasting money because of malabsorbed food. Three patterns of eating emerged: eating for survival, eating for health benefits, and eating for socialization. A proposed model illustrates how these eating patterns are linked to QOL. Being able to eat and enjoy food is an important ingredient for good self-reported QOL. Measurements of QOL for this population may be enhanced with inclusion of a food and eating domain. The social and emotional context of food and mealtimes is an important component to address in the nutrition care plan for PN-dependent adults. PMID- 21034882 TI - Parenteral nutrition-associated conjugated hyperbilirubinemia in hospitalized infants. AB - Parenteral nutrition-associated conjugated hyperbilirubinemia (PNAC), commonly defined as direct bilirubin >=2 mg/dL (34.2 MUmol/L), is primarily a pediatric disease with premature infants being the most susceptible. Severe morbidity and increased mortality are associated with bilirubin >10 mg/dL (171.0 MUmol/L). The lack of knowledge regarding the cause of PNAC has stymied development of prevention and treatment strategies. A systematic search of published reports was conducted to provide data on histopathology of PNAC and to review prospective, randomized, controlled trials in hospitalized infants. In experiments of young animals, parenteral nutrition (PN) with and without soy oil emulsion is directly linked to hyperbilirubinemia, and the effects are exaggerated by overfeeding. In infants, the most consistently reported risk factor for PNAC is the duration of PN. The only known effective modality is the transition to full enteral feeding and discontinuation of PN. Emerging clinical research is evaluating the role of lipid source (soy vs fish) and motility agents, such as erythromycin. Different trace element preparations are associated with varying severity of cholestasis, a finding that also deserves more study. This article reviews the prevalence, risk factors, clinical presentation, and treatment options for PNAC in neonatal intensive care units. PMID- 21034883 TI - Evaluation of a breastfeeding peer support program for fathers of Hispanic participants in a Texas special supplemental nutrition program for women, infants, and children. AB - A mother's decision to breastfeed and the duration of breastfeeding depends on different factors; among them are the support of her husband or male partner and other social support. There have been different types of support programs for mothers and few have targeted fathers. In 2002, the Texas Special Supplemental Nutrition Program for Women, Infants, and Children introduced an innovative approach for encouraging breastfeeding among mothers and their spouses. The pilot Peer Dad Program targeted fathers to promote and support their spouse in breastfeeding. This cohort study evaluated duration of breastfeeding among Hispanic couples who enrolled in the pilot Peer Dad Program (n=101) and those who did not enroll (n=99). Structured interviews were conducted with Special Supplemental Nutrition Program for Women, Infants, and Children participants and their male partners. Unconditional logistic regression was used to estimate the likelihood of continuing breastfeeding past 6 months associated with participation in the Peer Dad Program and significant predictors. Mothers whose partner participated in the pilot Peer Dad Program were no more likely to continue breastfeeding past 6 months (odds ratio 1.44, 95% confidence interval 0.82 to 2.54) compared with mothers who received peer counseling only. The percentage of women in the intervention group (63.4%) who breastfed for 6 months or longer compared with women in the control group (54.6%) was not significant (P=0.20). Although other studies suggest that father's support lengthens breastfeeding duration, our study, which targeted Hispanic fathers, found no association due to its small sample size. Further research with larger studies is needed to establish this association. PMID- 21034884 TI - Assessing the influence of registered dietitian order-writing privileges on parenteral nutrition use. AB - Previous studies have examined the influence of a nutrition support team on parenteral nutrition (PN) use; however, the influence of registered dietitian (RD) order-writing privileges on appropriate PN use has yet to be reported. A retrospective cohort was conducted at a single tertiary care urban academic medical center to compare adult PN use before RD order-writing privileges (January 1, 2003 to December 31, 2004, pre-privileges) to after RD order-writing privileges (January 1, 2006 to December 31, 2007, post-privileges). RD order writing privileges were obtained June 2005; PN patients during the washout period (January 1, 2005 to December 31, 2005) were not included. Descriptive statistics were conducted (N=1,965 patients). Although total hospital admissions increased from the pre-privileges to post-privileges periods (P<0.0001), overall PN use decreased from 1,080 patients during the pre-privileges period to 885 patients during the post-privileges period (P<0.0001). Inappropriate PN use decreased from 482 (45%) to 240 (27%) patients (P<0.0001) during the pre- and post-privileges periods, respectively. Among inappropriate PN use, there was a decrease in PN administration for patients with poor oral intake (130 to 41 patients), pancreatitis (78 to 26 patients), intractable nausea and vomiting (68 to 23 patients), and mucositis (56 to 18 patients; all Ps<0.0003), reflecting a 20% cost savings for PN. No significant differences were found in hospital length of stay, admissions to intensive care units, or other infectious complications between the two periods. RDs with order-writing privileges can decrease inappropriate PN use and costs in a hospital setting. Future studies should continue to highlight the influence of RDs in these advanced practice roles, as well as other members of the nutrition support team, especially with regard to nutrition support delivery and patient outcomes. PMID- 21034885 TI - Early effects of the federally mandated Local Wellness Policy on school nutrition environments appear modest in Colorado's rural, low-income elementary schools. AB - To increase opportunities for healthy eating and physical activity, US school districts participating in the National School Lunch Program were required to create a Local Wellness Policy (LWP) by June 2006. The What's Working project described the initial influence of this mandate on nutrition environments and policies. In 2005 and 2007 (before and after the mandate went into effect), a survey about school features related to nutrition and physical activity was sent to a random sample of 45 low-income, rural elementary foodservice managers and principals. Schools averaged 204 students, 27% Hispanic. Districts' LWPs were coded for strength and comprehensiveness. In addition, key informant interviews were conducted with foodservice managers almost 2 years after the LWP went into effect. Three improvements were observed: increases in the percent of schools with policies stipulating predominantly healthy items be offered in classroom parties (21.4% in 2005 vs 48.7% in 2007), daily fresh fruit offerings in the lunchroom (0.80 choices in 2005 vs 1.15 choices in 2007), and the percent of schools using skinless poultry (27% in 2005 vs 59% in 2007). LWPs were weakly worded and rarely addressed energy content. Nutrition guideline elements most commonly addressed included vending machines, school stores, and a la carte food offerings. Seveny-three percent of foodservice managers were familiar with their district's LWP but did not perceive it changed lunchroom practices. Although LWPs offer a framework to support opportunities for healthy eating, few evidence-based practices were implemented as a direct result of the mandate. Schools need more information about evidence-based practices, as well as technical and financial assistance for implementation. PMID- 21034886 TI - Associations between children's appetitive traits and maternal feeding practices. AB - This study explored associations between child eating behaviors and maternal feeding practices, specifically testing the hypotheses that maternal "restriction" is associated with having a child with stronger food approach tendencies (eg, overresponsiveness to food), and maternal pressure to eat is associated with having a child with food avoidant tendencies (eg, satiety responsiveness). Five-hundred thirty-one families with 7- to 9-year-old children from schools in London, UK, were invited to take part in the Physical Exercise and Appetite in Children Study (PEACHES). Results are from baseline data of this longitudinal study. Of those invited, 405 gave consent for their child to participate (51.6% male; 48% female). Just over half of the mothers (n=213, 53%) completed the Child Eating Behavior Questionnaire and the Child Feeding Questionnaire for the index child (mean age: 8.3+/-0.62 years) during the 2006 2007 school year. Children were weighed and measured at school by trained researchers. As predicted, maternal restriction was associated with child food responsiveness (P<0.001), and maternal pressure to eat was associated with child satiety responsiveness (P<0.001), slowness (P=0.03), and fussiness (P=0.01). Child enjoyment of food was associated with lower maternal pressure to eat (P=0.01). All effects were independent of the child's body mass index standard deviation score and sociodemographic factors. Practitioners may find it useful to take an interactional perspective, acknowledging that children both influence and are influenced by their parents' feeding practices. This will allow the development of targeted interventions and better parental guidance on managing obesogenic eating behaviors in young children. PMID- 21034887 TI - Web-based nutrition education intervention improves self-efficacy and self regulation related to increased dairy intake in college students. AB - Dairy consumption declines substantially during young adulthood. Interventions that incorporate theory-based nutrition education can provide insight into factors associated with dietary choices. The aim of this experimental study was to improve outcome expectations, self-efficacy, self-regulation, and behavior related to dairy intake in college students using social cognitive theory. Students (n=294) enrolled in a personal health class were randomized to intervention (n=148) or comparison group (n=146). The 5-week intervention (March 2006 to April 2006) was conducted using an online course system; components included e-mail messages, posted information, and behavior checklists with tailored feedback. Multivariate analysis of covariance with age and sex as covariates (P<0.05) was conducted to measure change related to dairy intake and social cognitive theory variables. Ninety-two percent of participants (n=135 intervention, n=136 control) completed the study. Dairy intake from food records did not differ between groups at baseline; baseline intake for all participants (mean +/- standard error) was 0.45 +/- 0.05 servings/day for low-fat dairy products and 1.44 +/- 0.06 servings/day for total dairy products. Participants in the intervention group made greater increases in use of self-regulatory strategies (P=0.038) and self-efficacy for consuming three servings/day of dairy products (P=0.049), but not in outcome expectations or consumption of dairy products. A Web-based intervention designed to change dairy intake in college students was effective in modifying some social cognitive theory constructs; strategies that positively impact outcome expectations and social support through online interventions require further development. PMID- 21034888 TI - Tolerance of an enteral formula with insoluble and prebiotic fiber in children with compromised gastrointestinal function. AB - The effects of adding fiber to the tolerance of a peptide-based formula have not been studied. The objective of this study was to evaluate the tolerance of a peptide-based formula with insoluble and prebiotic fiber in children with compromised gut function. During January 2005 to June 2006, a 6-week randomized, double-blind, cross-over clinical study was conducted to compare stool frequency, stool consistency, and tolerance (abdominal pain, abdominal distension, vomiting, weight gain, and intake) between a formula with or without 3.5 g fructo oligosaccharides and 3.8 g insoluble fiber/L. Fourteen children with gastrointestinal dysmotility (n=9), Crohn's disease (n=3), or mild short bowel syndrome (n=2) were randomized to receive one of two formulas for 2 weeks followed by a 5-day washout period and then the second diet for another 2 weeks. Means and standard deviations of daily stool frequency and consistency were calculated and compared using intent-to-treat analysis. Linear mixed models were applied to each outcome variable. Stool frequency did not differ by formula. Stool consistency did differ with more soft "mushy" stools (less hard stools) occurring with use of fiber (P<0.001) and more watery stools occurring with control formula (P<0.01). The extremes of stool consistency were normalized with the fiber formula. No significant differences were observed in vomiting, abdominal pain, feeding intakes, or weight gain between the two formulas. This study showed that a peptide-based formula containing fiber was as well-tolerated as a fiber-free formula in a small population of children with gastrointestinal impairments. Longer-term effects of the fiber formula need to be studied. PMID- 21034889 TI - Acute bariatric surgery complications: managing parenteral nutrition in the morbidly obese. PMID- 21034890 TI - What is the anti-inflammatory diet? PMID- 21034891 TI - A randomized trial comparing uncovered and partially covered self-expandable metal stents in the palliation of distal malignant biliary obstruction. AB - BACKGROUND: The most common complication of uncovered biliary self-expandable metal stents (SEMSs) is tumor ingrowth. The addition of an impenetrable covering may prolong stent patency. OBJECTIVE: To compare stent patency between uncovered and partially covered SEMSs in malignant biliary obstruction. DESIGN: Multicenter randomized trial. SETTING: Four teaching hospitals. PATIENTS: Adults with inoperable distal malignant biliary obstruction. INTERVENTIONS: Uncovered or partially covered SEMS insertion. MAIN OUTCOME MEASURES: Time to recurrent biliary obstruction, patient survival, serious adverse events, and mechanism of recurrent biliary obstruction. RESULTS: From October 2002 to May 2008, 129 patients were randomized. Recurrent biliary obstruction was observed in 11 of 61 uncovered SEMSs (18%) and 20 of 68 partially covered SEMSs (29%). The median times to recurrent biliary obstruction were 711 days and 357 days for the uncovered and partially covered SEMS groups, respectively (P = .530). Median patient survival was 239 days for the uncovered SEMS and 227 days for the partially covered SEMS groups (P = .997). Serious adverse events occurred in 27 (44%) and 42 (62%) patients in the uncovered and partially covered SEMS groups, respectively (P = .046). None of the uncovered and 8 (12%) of the partially covered SEMSs migrated (P = .0061). LIMITATIONS: Intended sample size was not reached. Allocation to treatment groups was unequal. CONCLUSIONS: There was no significant difference in time to recurrent biliary obstruction or patient survival between the partially covered and uncovered SEMS groups. Partially covered SEMSs were associated with more serious adverse events, particularly migration. PMID- 21034892 TI - Covered versus uncovered self-expandable nitinol stents in the palliative treatment of malignant distal biliary obstruction: results from a randomized, multicenter study. AB - BACKGROUND: Covered biliary metal stents have been developed to prevent tumor ingrowth. Previous comparative studies are limited and often include few patients. OBJECTIVE: To compare differences in stent patency, patient survival, and complication rates between covered and uncovered nitinol stents in patients with malignant biliary obstruction. DESIGN: Randomized, multicenter trial conducted between January 2006 and October 2008. SETTING: Ten sites serving a total catchment area of approximately 2.8 million inhabitants. PATIENTS: A total of 400 patients with unresectable distal malignant biliary obstruction. INTERVENTIONS: ERCP with insertion of covered or uncovered metal stent. Follow-up conducted monthly for symptoms indicating stent obstruction. MAIN OUTCOME MEASUREMENTS: Time to stent failure, survival time, and complication rate. RESULTS: The patient survival times were 116 days (interquartile range 242 days) and 174 days (interquartile range 284 days) in the covered and uncovered stent groups, respectively (P = .320). The first quartile stent patency time was 154 days in the covered stent group and 199 days in the uncovered stent group (P = .326). There was no difference in the incidence of pancreatitis or cholecystitis between the 2 groups. Stent migration occurred in 6 patients (3%) in the covered group and in no patients in the uncovered group (P = .030). LIMITATIONS: Randomization was not blinded. CONCLUSIONS: There were no significant differences in stent patency time, patient survival time, or complication rates between covered and uncovered nitinol metal stents in the palliative treatment of malignant distal biliary obstruction. However, covered stents migrated significantly more often compared with uncovered stents, and tumor ingrowth was more frequent in uncovered stents. PMID- 21034893 TI - All wrapped up: metal biliary stents and the effect of stent coverings. PMID- 21034894 TI - Efficacy and safety of biodegradable stents for refractory benign esophageal strictures: the BEST (Biodegradable Esophageal Stent) study. AB - BACKGROUND: Benign esophageal strictures refractory to standard dilation therapy present a challenging problem. Temporary plastic and metal stents have been proposed with inconclusive results. OBJECTIVE: To evaluate the efficacy and safety of a new biodegradable stent for the treatment of refractory benign esophageal strictures (RBESs). DESIGN AND SETTING: Prospective study from 2 European endoscopy centers. PATIENTS AND INTERVENTION: Twenty-one patients (11 men/10 women, mean age 60.2 +/- 17.6 years) with RBESs defined according to the Kochman criteria treated by placement of a biodegradable stent (Ella stent). MAIN OUTCOME MEASUREMENTS: Clinical and endoscopic follow-up was scheduled at 1, 2, 3, and 6 months and later only in case of dysphagia recurrence. Pre- and poststenting dysphagia status was graded according to a 5-point scale. Minor and major complication rates were prospectively assessed. RESULTS: Stent insertion was technically successful in all of the patients. At 4 and 7 weeks, stent migration occurred in 2 patients (9.5%). At 3-month endoscopy, the stent appeared to be almost completely fragmented in all remaining patients. The median pre- and poststenting dysphagia scores were 3 (range 3-4) and 1 (range 0-2), respectively (P < .01), with a median follow-up of 53 weeks (range 25-88 weeks). In detail, 9 of 20 patients (45%) were dysphagia free at the end of the follow-up. No major complications occurred. Severe poststenting pain requiring analgesics developed in 3 patients, and minor bleeding was observed in 1 patient. LIMITATIONS: Limited follow-up; nonrandomized study. CONCLUSIONS: In this preliminary study, the biodegradable stent showed a favorable risk/benefit ratio, achieving complete relief of dysphagia in nearly 50% of RBES patients without the occurrence of major complications. The use of this stent may be a valuable alternative to repeat endoscopic dilation. Larger studies with longer follow-up are needed. PMID- 21034895 TI - Randomized comparison of 3 different-sized biopsy forceps for quality of sampling in Barrett's esophagus. AB - BACKGROUND: Several types of forceps are available for use in sampling Barrett's esophagus (BE). Few data exist with regard to biopsy quality for histologic assessment. OBJECTIVE: To evaluate sampling quality of 3 different forceps in patients with BE. DESIGN: Single-center, randomized clinical trial. PATIENTS: Consecutive patients with BE undergoing upper endoscopy. INTERVENTIONS: Patients randomized to have biopsy specimens taken with 1 of 3 types of forceps: standard, large capacity, or jumbo. MAIN OUTCOME MEASUREMENTS: Specimen adequacy was defined a priori as a well-oriented biopsy sample 2 mm or greater in diameter and with at least muscularis mucosa present. RESULTS: A total of 65 patients were enrolled and analyzed (standard forceps, n = 21; large-capacity forceps, n = 21; jumbo forceps, n = 23). Compared with jumbo forceps, a significantly higher proportion of biopsy samples with large-capacity forceps were adequate (37.8% vs 25.2%, P = .002). Of the standard forceps biopsy samples, 31.9% were adequate, which was not significantly different from specimens taken with large-capacity (P = .20) or jumbo (P = .09) forceps. Biopsy specimens taken with jumbo forceps had the largest diameter (median, 3.0 mm vs 2.5 mm [standard] vs 2.8 mm [large capacity]; P = .0001). However, jumbo forceps had the lowest proportion of specimens that were well oriented (overall P = .001). LIMITATIONS: Heterogeneous patient population precluded dysplasia detection analyses. CONCLUSIONS: Our results challenge the requirement of jumbo forceps and therapeutic endoscopes to properly perform the Seattle protocol. We found that standard and large-capacity forceps used with standard upper endoscopes produced biopsy samples at least as adequate as those obtained with jumbo forceps and therapeutic endoscopes in patients with BE. PMID- 21034896 TI - EUS in patients with surgically altered upper GI anatomy. AB - BACKGROUND: Information regarding the safety and feasibility of EUS-guided FNA (EUS/FNA) in surgically altered anatomy is limited. OBJECTIVE: The aim of this study was to describe EUS outcomes for Billroth I and II, Whipple, Puestow, Roux en-Y (including gastric bypass), esophagectomy, and Nissen fundoplication surgeries. DESIGN: Retrospective study. SETTING: Single tertiary-care center. PATIENTS: This study involved 188 EUS procedures performed in patients with surgically altered anatomy by 6 endosonographers from July 1995 to October 2008. INTERVENTION: EUS and FNA. MAIN OUTCOME MEASUREMENTS: Type of surgery, EUS indication, limitations to imaging, reasons for limitations, FNA results, and EUS/FNA complications. RESULTS: Of 188 patients, 96 were men (mean age 57 years; range, 16-92 years). Of patients with Billroth II anatomy (n = 39), 10 had limited (common bile duct [CBD], head of pancreas [HOP]) imaging because intubation of the afferent limb failed (n = 6) or was not attempted (n = 4). Roux en-Y (n = 18) encompased a variety of surgeries, but in general (n = 13) the proximal duodenum was not reached and the HOP and CBD were not imaged. For Roux en-Y gastric bypass (n = 7), the HOP and CBD were not imaged, with the exception of 1 case (in which staple-line dehiscence permitted access to the proximal duodenum). For the remaining procedures, EUS and FNA were successful with few exceptions. There were no significant adverse events (95% confidence interval, 0% to 1.9%). LIMITATIONS: Retrospective descriptive study. CONCLUSION: EUS is generally successful and safe in patients with surgically altered anatomy in this tertiary-care setting, and a very low rate of adverse events is possible. Exceptions included imaging the HOP and CBD after Roux-en-Y surgery. After Billroth II surgery, if the afferent limb was intubated, the majority of patients were able to have a complete pancreaticobiliary examination, including FNA. PMID- 21034897 TI - Superficial adenocarcinoma of the esophagogastric junction: long-term results of endoscopic submucosal dissection. AB - BACKGROUND: Endoscopic submucosal dissection (ESD) was recently introduced as a treatment option for superficial adenocarcinoma of the esophagogastric junction (EGJ); however, its long-term clinical outcomes have not been fully evaluated. OBJECTIVE: To assess the long-term outcomes of ESD for patients with superficial adenocarcinoma of the EGJ. DESIGN: Retrospective review from a single institution. SETTING: University hospital. PATIENTS: Fifty-eight patients, 46 men and 12 women (mean 69.3 years), with 39 T1m and 19 T1sm adenocarcinomas of the EGJ treated from June 2000 to May 2009. INTERVENTIONS: ESD procedures were performed with typical sequences. MAIN OUTCOME MEASUREMENTS: Complications, en bloc resection rate, curative resection rate, local recurrence, and distant metastases after ESD were evaluated. Curative resection is histologically defined as being free of resection margins and any evidence of deep submucosal invasion, undifferentiated carcinoma, and lymphovascular invasion. RESULTS: There were no major complications except for 3 patients with ulcer bleeding without the need for blood transfusion and 1 patient with esophageal stenosis. The rates of en bloc resection and curative resection were 100% and 79%, respectively. Twelve resections were histologically considered noncurative; these patients underwent additional ESD (n = 1) or surgical resection (n = 8). Local or distant recurrences were not observed in any patient achieving curative resection during follow-up (median 36.6 months, range 4-94 months). LIMITATIONS: Retrospective design and single-site data collection. CONCLUSIONS: Long-term outcomes after ESD are favorable. ESD may be adopted as a treatment of choice for superficial adenocarcinoma of the EGJ. PMID- 21034898 TI - EUS in the initial assessment of upper abdominal pain: time for a paradigm shift? PMID- 21034899 TI - Challenges in planning and initiating a randomized clinical study of sphincter of Oddi dysfunction. AB - BACKGROUND: Sphincter of Oddi dysfunction (SOD) is a controversial topic, especially in patients with no objective findings on laboratory or imaging studies (SOD type III). The value of ERCP manometry with sphincterotomy is unproven and carries significant risks. OBJECTIVE: To describe the process of planning and initiating a randomized sham-controlled study to establish whether patients with SOD respond to sphincter ablation, and whether the outcomes are predicted by the pain patterns, presence or absence of other functional GI or psychosocial problems, or the results of manometry. DESIGN: Planning a trial to establish which patients with "suspected SOD" (if any) respond to endoscopic sphincter ablation. SETTING: Meetings and correspondence by a planning group of gastroenterologists and clinical research specialists hosted at the Medical University of South Carolina. PATIENTS: Clarifying subject characteristics and inclusion and exclusion criteria. INTERVENTIONS: Defining the questionnaires, therapies, randomizations, and numbers of subjects required by outcome measures. Defining the metrics of success and failure. RESULTS: The planning resulted in funding for the proposed study as a cooperative agreement with the National Institute of Diabetes and Digestive and Kidney Diseases. LIMITATIONS: Lack of data required several consensus decisions in designing the protocol. CONCLUSION: The planning process was challenging, and some changes were needed after initiation. PMID- 21034900 TI - A novel modality for the estimation of the enteroscope insertion depth during double-balloon enteroscopy. AB - BACKGROUND: Until now, the insertion depth of the enteroscope during double balloon enteroscopy (DBE) could only be estimated. However, the currently available methods have limitations, and development of newer, simple, and accurate modalities is needed. OBJECTIVE: To evaluate the accuracy of a novel method for evaluation of enteroscope insertion depth during DBE. DESIGN: Prospective, single-center cohort study. SETTING: Tertiary referral university hospital. PATIENTS: Fifty-one patients who had lesions found during 41 antegrade and 10 retrograde DBEs and treated by surgery were enrolled in this study. INTERVENTIONS: The length of the ligament of Treitz/ileocecal valve lesion was estimated by adding the forward enteroscope length during each cycle of passage and by calculating the overtube insertion length (every 5 cm of overtube advancement means 40 cm of enteroscope advancement based on preliminary observations) during DBE, respectively, and was evaluated at surgery. MAIN OUTCOME MEASUREMENTS: The length from the ligament of Treitz/ileocecal valve to the lesion. RESULTS: Surgical evaluation was used as the standard. Regardless of insertion route, the mean difference from surgery in evaluation of enteroscope insertion length between using the enteroscope method and the overtube method was 19 cm (range 0-50 cm) and 17 cm (range 0-60 cm), respectively (P > .05). LIMITATIONS: Small number of patients with a case series study design. CONCLUSIONS: Calculating the length of the overtube passage is accurate, and it is simple to estimate the insertion depth of the enteroscope during DBE, which is useful in clinical practice. PMID- 21034901 TI - Autofluorescence imaging with a transparent hood for detection of colorectal neoplasms: a prospective, randomized trial. AB - BACKGROUND: Colonoscopy is one of the most reliable methods for detection of colorectal neoplasms, but conventional colonoscopy can miss some lesions. OBJECTIVE: To evaluate the efficacy of autofluorescence imaging (AFI) with a transparent hood (TH) for detection of colorectal neoplasms. DESIGN: A 2 * 2 factorial designed, prospective, randomized, controlled trial. SETTING: This study was conducted at the Osaka Medical Center for Cancer and Cardiovascular Diseases, a tertiary cancer center. PATIENTS: A total of 561 patients. INTERVENTIONS: Patients were allocated to 1 of 4 groups: (1) white light imaging (WLI) alone--colonoscopy using WLI without a TH; (2) WLI+TH--colonoscopy using WLI with a TH; (3) AFI alone--colonoscopy using AFI without a TH; and (4) AFI+TH- colonoscopy using AFI with a TH. Eight colonoscopists used each allocated method. MAIN OUTCOME MEASUREMENT: The difference in neoplasm detection rate (number of detected neoplasms per patient) between the WLI alone and AFI+TH groups. RESULTS: Neoplasm detection rate (95% confidence interval) in the AFI+TH group was significantly higher than in the WLI alone group (1.96 [1.50-2.43] vs 1.19 [0.93 1.44]; P = .023, Tukey-Kramer multiple comparison test). Relative detection ratios (95% confidence interval) for polypoid neoplasms based on Poisson regression model were significantly increased by mounting a TH (1.69 [1.34-2.12], P < .001), and relative detection ratios for flat neoplasms were significantly increased by AFI observation (1.83 [1.24-2.71], P = .002). LIMITATIONS: Open trial performed in single cancer referral center. CONCLUSION: AFI colonoscopy with a TH detected significantly more colorectal neoplasms than did conventional WLI colonoscopy without a TH. PMID- 21034903 TI - Natural orifice transluminal endoscopic surgery: looking beyond the gallbladder. PMID- 21034902 TI - Clip closure versus endoscopic suturing versus thoracoscopic repair of an iatrogenic esophageal perforation: a randomized, comparative, long-term survival study in a porcine model (with videos). AB - BACKGROUND: Esophageal full-thickness wall repair is an important but unsolved issue in endoscopy. It is unknown how well endoscopic clip closure (ECC) and endoscopic closure with suturing (ECS) perform compared with the criterion standard of thoracoscopic closure (TC). OBJECTIVE: Comparison of technical success, feasibility, long-term patency, complications, and histological quality of the different closure techniques (ECC, ECS, TC) for esophageal perforations. DESIGN: Comparative animal study. SETTING: Approved animal facility. SUBJECTS: Eighteen pigs. INTERVENTIONS: Eighteen pigs were randomized, 6 each into 3 groups (ECC, ECS, TC). After endoscopic wall incision and mediastinoscopy, closure was performed by using 1 of the 3 techniques. After 8 to 12 weeks, pre-euthanasia endoscopic, necropsy, histological, and morphometric analyses were performed. MAIN OUTCOME MEASUREMENT: Long-term survival and histological quality of the repair. RESULTS: The closure of the esophageal incisions was successful in all pigs. On days 2 and 6, 1 animal died of mediastinitis, 1 in the ECS group because of reflux of gastric contents into the mediastinum before the repair and 1 in the TC group because of leakage of the sutured closure (P = 1.0). No strictures were seen on prenecropsy endoscopy. At necropsy, 1 mediastinal abscess was found in an ECS animal (P = 1.0). Minor complications included periesophageal adhesions and reactive lymph nodes in 3 of 6 (ECC group) and 5 of 6 (TC and ECS groups). Histology showed muscle layer defects up to 12 mm in width and 21 mm in length, with a trend toward smaller defect size of width and length in the ECS group of animals. LIMITATIONS: Animal study of limited size. CONCLUSIONS: Overall, ECS and ECC performed similarly to TC. ECS showed the smallest histological defects in the long-term repair. PMID- 21034904 TI - Current affairs: electrosurgery in the endoscopy suite. PMID- 21034905 TI - Quantitative analysis and development of a computer-aided system for identification of regular pit patterns of colorectal lesions. AB - BACKGROUND: Because pit pattern classification of colorectal lesions is clinically useful in determining treatment options for colorectal tumors but requires extensive training, we developed a computerized system to automatically quantify and thus classify pit patterns depicted on magnifying endoscopy images. OBJECTIVE: To evaluate the utility and limitations of our automated pit pattern classification system. DESIGN: Retrospective study. SETTING: Department of endoscopy at a university hospital. MAIN OUTCOME MEASUREMENTS: Performance of our automated computer-based system for classification of pit patterns on magnifying endoscopic images in comparison to classification by diagnosis of the 134 regular pit pattern images by an endoscopist. RESULTS: For type I and II pit patterns, the results of discriminant analysis were in complete agreement with the endoscopic diagnoses. Type IIIl was diagnosed in 29 of 30 cases (96.7%) and type IV was diagnosed in 1 case. Twenty-nine of 30 cases (96.7%) were diagnosed as type IV pit pattern. The overall accuracy of our computerized recognition system was 132 of 134 (98.5%). CONCLUSIONS: Our system is best characterized as semiautomated but is a step toward the development of a fully automated system to assist in the diagnosis of colorectal lesions based on classification of pit patterns. PMID- 21034906 TI - Onset of gastric Crohn's disease observed endoscopically. PMID- 21034907 TI - Cavernous hemangiomas limited to the sigmoid colon. PMID- 21034908 TI - Pancreatic antegrade needle-knife (PANK) for treatment of symptomatic pancreatic duct obstruction in Whipple patients (with video). AB - BACKGROUND: Endoscopic decompression of symptomatic main pancreatic duct (MPD) dilation in Whipple patients is often difficult because of stenosis of the pancreaticojejunal (PJ) anastomosis. OBJECTIVE: To evaluate the feasibility and procedural safety of the pancreatic antegrade needle-knife (PANK) technique, with the goal of restoring antegrade MPD flow, when endoscopic retrograde pancreatography (ERP) and EUS-guided rendezvous fail. SETTING: Tertiary care center. DESIGN: Retrospective series. PATIENTS: Three patients with symptomatic MPD dilation refractory to ERP and EUS-guided rendezvous. INTERVENTIONS: Under EUS guidance, a 19-gauge echo-needle was used to gain access to the dilated MPD and a Jagwire advanced. After failed attempts at antegrade guidewire passage across the PJ stenosis, deep transgastric MPD access was achieved via a Soehendra stent retriever and balloon dilation. Careful antegrade needle-knife of the stenotic site was performed. A long pancreatic stent spanning the jejunum, MPD, and gastric access site was placed. Four to 8 weeks later, this stent was upsized and converted to a PJ stent, which in turn was removed 4 weeks thereafter. MAIN OUTCOME MEASUREMENTS: Technical feasibility and complications. RESULTS: All 3 patients successfully underwent the PANK procedure. Pre- and post-MRCP studies showed the mean MPD diameter decreased 60% from 8.3 mm to 3.6 mm (mean follow-up 8 months). At 24-month follow-up, all 3 patients experienced decreased or resolved pain without further need for MPD intervention. LIMITATIONS: Retrospective study with small numbers. CONCLUSIONS: When ERP and EUS rendezvous fail, the PANK procedure using a staged stent strategy seems to be an effective means of MPD decompression. PMID- 21034909 TI - EUS-guided tattooing before laparoscopic distal pancreatic resection (with video). AB - BACKGROUND: Precise localization of small pancreatic tumors during laparoscopic distal pancreatectomy (LDP) can be difficult because of decreased tactile ability of laparoscopy and the homogeneous appearance of the pancreas and surrounding retroperitoneal fat. Precise localization of the lesion is critical to achieving adequate margins of resection and preserving healthy pancreatic tissue. EUS guided fine-needle tattooing (EUS-FNT) of a pancreatic lesion before LDP has been described in single case reports, but no large series have reported its effectiveness in patients undergoing LDP. OBJECTIVE: To assess the feasibility, safety, and efficacy of EUS-FNT in consecutive patients undergoing LDP. DESIGN: Retrospective cohort study. SETTING: Tertiary-care referral hospital. PATIENTS: This study involved 30 consecutive patients who underwent LDP from 2008 to 2010. Thirteen had EUS-FNT followed by LDP, and 17 had LDP alone. INTERVENTIONS: LDP or EUS-FNT with a sterile carbon-particle tattoo followed by LDP. MAIN OUTCOME MEASUREMENTS: The following features were examined: the technical success and complication rates of EUS-FNT, visibility of the tattoo at the time of laparoscopy, durability of the tattoo, and pathologic absence of tumor at the resection margin. RESULTS: The final pathology of pancreatic lesions of patients who had EUS-FNT was similar to those who had LDP alone. The median resected tumor size was significantly larger for the LDP-alone patients (median 4.0 cm vs 1.3 cm; P = .03). Thirty-one percent (4/13) of lesions in the EUS-FNT group were not visualized by prior preoperative pancreatic protocol CT. EUS-FNT was feasible in all 13 patients at laparoscopy, with R0 resection and negative final pathology margins in all cases. The tattoo was visible in all 13 EUS-FNT cases, with mean time from EUS-FNT to surgery of 20.3 days (range, 3-69 days). There were no significant complications associated with EUS-FNT. LIMITATIONS: Small, retrospective, single-center study. CONCLUSIONS: Preoperative EUS-FNT of lesions was technically feasible and safe, and it assisted in the localization of lesions in patients before LDP. The carbon particle tattoo was durable and visible in all cases. PMID- 21034910 TI - Is cyanoacrylate therapy really better than transjugular intrahepatic portosystemic shunt for preventing gastric variceal rebleeding? PMID- 21034911 TI - Gender disparities and gastroenterology trainee attitudes toward advanced endoscopic training. PMID- 21034913 TI - Could a higher rebleeding rate for bleeding peptic ulcers in patients with renal failure be an artifactual finding? PMID- 21034914 TI - Double channel does it all: both visualization and deployment in half the time. PMID- 21034915 TI - It's not the precut; it's the why done and who by. PMID- 21034916 TI - The influence of fellow involvement and level of fellowship training on adenoma detection rates. PMID- 21034918 TI - ERCP by laparoscopic transgastric access and cholecystectomy at the same time in a patient with gastric bypass who was seen with choledocholithiasis. PMID- 21034920 TI - Appendiceal carcinoid tumor with lymph node metastasis in a child: case report and review of the literature. AB - Most appendiceal carcinoids (ACs) in children present without lymph node metastasis. Lymph node metastasis is rarely present when primary tumor diameter exceeds 1 cm. We present the extraordinary case of an AC with a primary tumor diameter of 0.7 cm and infiltration of the mesentery, as well as 1 positive lymph node of the mesentery in a 14-year-old boy. Besides adding a rare case, we review the data published in the current literature on AC with lymph node metastasis in children and summarize up-to-date guidelines for diagnostic workup, therapy, and follow-up. PMID- 21034921 TI - Ureteral damage during appendicectomy. AB - A case of right ureteric damage in a 7-year-old boy who underwent appendicectomy is described. Ultrasound, magnetic resonance urography, nephrostogram, and retrograde ureterogram were helpful in defining the nature and extent of the lesion. He underwent staged procedures of percutaneous nephrostomy, elective resection and reconstruction of midureteral segment, and subsequent removal of double J stent and made a smooth recovery. Ureteric injuries, although rare, have serious consequences. A high index of suspicion is essential for diagnosis. Management is influenced by site, type, extent, and mechanism of injury, as well as the timing of detection. PMID- 21034922 TI - Retropleural teratoma presenting as an abdominal mass in a 9-month-old boy. AB - BACKGROUND: Teratomas are rare tumors that present most commonly in the anterior mediastinum and retroperitoneum. To date, the retropleural primary site has not been reported. CASE PRESENTATION: A 9-month-old boy presented with a large, painless, right-sided abdominal mass. Laboratory values, including tumor markers alpha-fetoprotein and beta-human chorionic gonadotropin, were within normal limits. Diagnostic imaging, including abdominal ultrasound, computed tomographic scan, and magnetic resonance imaging, suggested a large retroperitoneal mass consistent with a teratoma. Because the mass was thought to be arising from the retroperitoneum, an abdominal approach was chosen. After adequate exposure, it became clear that the tumor was arising from above the diaphragm. The diaphragm was incised, and the pleural cavity was entered. The tumor was found in the retropleural space where it was dissected away from the inferior vena cava, aorta, and chest wall. The patient recovered without complications. RESULTS: Histologic examination revealed a mature cystic teratoma with no malignant features. The patient has been disease-free at 7-year follow-up, based upon both clinical examination and diagnostic imaging. CONCLUSION: This is the first case report of a teratoma arising from the retropleural space. Preoperative imaging may be inaccurate for guiding surgical planning because the diaphragm may not be clearly visualized with current diagnostic techniques. Surgeons should be cautious regarding the location of tumors that arise near the diaphragm and should plan surgical resection carefully. PMID- 21034923 TI - Hypertrophic osteoarthropathy in intestinal transplant recipients. AB - We report 3 patients with periosteal new bone formation consistent with hypertrophic osteoarthropathy (HOA), in the context of intestinal allograft rejection. Patient 1 developed thick periosteal new bone formation of the right arm during a prolonged episode of intestinal acute cellular rejection (ACR) 2 months posttransplant. Patient 2 developed ankle pain and swelling during an episode of severe ACR. Plain films showed periosteal new bone formation of the left ankle. In patient 3, the right wrist became swollen during an episode of moderate ACR, whereas plain films demonstrated mild periosteal reaction. Patients 2 and 3 had resolution of their symptoms once the ACR resolved with treatment. This is the first case series of HOA occurring in association with intestinal ACR. We speculate that an immune-mediated process is responsible for the bone disease. Further inquiry will help establish if HOA is related to transplant status, intestinal inflammation, or allograft rejection in general. PMID- 21034924 TI - Hepatoblastoma in association with bilateral polycystic kidneys. AB - We describe the first known case of hepatoblastoma associated with bilateral autosomal recessive polycystic kidney disease in a preterm twin boy. The diagnostic and therapeutic considerations are addressed. The patient survived after primary hepatectomy operation and administration of modified adjuvant chemotherapy. PMID- 21034925 TI - Pilonidal cyst involving the clitoris in an 8-year-old girl--a case report and literature review. AB - Pilonidal disease is common among adolescents and adults, mainly located in the sacral area. Pilonidal disease involving the clitoris is extremely rare and has not been described in premenarcheal girls. We present a case of a recurrent pilonidal periclitoral cyst in an 8-year-old girl which was surgically treated. PMID- 21034926 TI - Complicated rectal prolapse in an infant: strangulated pararectal hernia. AB - Rectal prolapse is common in infants and children. It should initially be managed conservatively, as prolapse often resolves with the growth of the child. We encountered an 8-month-old infant with complete rectal prolapse associated with pararectal herniation of ileum between the 2 walls of the prolapsed rectum. This rare event led to strangulation of the ileal segment within the prolapsed rectal walls. We present this extremely uncommon case with a brief review of the relevant literature. PMID- 21034927 TI - Rectocele in children: a case report. AB - Rectocele is an abnormal protrusion of the anterior wall of the rectum into the vagina. When symptomatic, it will typically cause obstructed defecation. It is almost exclusively found in females with rare reports in males and never been described in the literature in children younger than 18 years of age so far. We are presenting 3 cases of rectocele with obstructed defecation in the pediatric population. These children presented with the complaints of constipation along with refractory straining. They were diagnosed by defecography. Two were treated surgically and one conservatively. Surgical intervention completely cured the problem with uneventful postoperative course. Further multicenter studies with the aid of radiologic studies on children with "hard to treat" constipation should be considered to better define that disorder in the pediatric age group. A more vigilant approach may have implications in the prevention of more severe rectal and uterovaginal prolapse in the future. PMID- 21034928 TI - Prune belly syndrome associated with cloacal anomaly, patent urachal remnant, and omphalocele in a female infant. AB - Prune belly syndrome (PBS), megacystis-microcolon-intestinal hypoperistalsis (MMIH), and omphalocele-exstrophy of the bladder-imperforate anus-spine abnormalities complex (OEIS) are rare congenital malformations of the newborn that lead to incomplete formation of the gastrointestinal and genitourinary tract systems. To date, incomplete mesodermal development is identified as the cause for all these complex genetic syndromes even if the etiology is still unknown. We present an original case sharing characteristics common to PBS, MMIH, and OEIS complex, without a clear inclination toward any particular one. This case hints toward a common pathway in the creation of the 3 syndromes. We hypothesize that they are a spectrum of malformations based on the time frame when the mesoderm fails to create a normal interaction between infraumbilical mesoderm, urorectal septum, lumbosacral somites in the formation of the abdominal wall and the genitourinary and lower gastrointestinal tracts. PMID- 21034929 TI - Bilateral ureteropelvic junction obstruction presenting with hypertension and cerebral vascular accident. AB - Cerebrovascular accident and renal hypertension secondary to ureteropelvic junction obstruction (UPJO) are extremely rare. A 6-year-old girl presented with intracranial hemorrhage because of hypertension secondary to the bilateral UPJO. This was successfully treated with craniotomy and subsequent percutaneous nephrostomy placement and bilateral pyeloplasty. Brain computerized tomography revealed right-sided intracranial hemorrhage, and renal ultrasonography confirmed bilateral severe hydronephrosis. Craniotomy with evacuation of intracerebral hematoma and bilateral nephrostomy under ultrasound guidance were performed. One week later, she underwent bilateral pyeloplasty in 2 stages. The patient has been well with normalized renal function and is completely cured of her hypertension in long-term follow-up. PMID- 21034930 TI - Is there a benefit of peritoneal drainage for necrotizing enterocolitis in newborn infants? PMID- 21034931 TI - Diagnosis and management of biliary cystic malformations in neonates. AB - PURPOSE: Recent advances in ultrasonography have made it possible to identify biliary atresia (BA) and choledochal cyst (CC) with biliary cystic malformations (BCM) both prenatally and neonatally. The early differential diagnosis between BA and CC is extremely important because operations must be performed as soon as possible before the livers of BA patients advance to an irreversible cirrhotic stage. The aim of this study was to differentiate patients with BCM and to determine the best course of management in the neonatal period. METHODS: The medical records of patients that were diagnosed with BCM by a prenatal or neonatal ultrasound between 1997 and 2008 were reviewed. We retrospectively divided the BCM patients into the BA and CC groups and then compared the results of ultrasound, computed tomography, and laboratory tests between the 2 groups. RESULTS: Ten patients were enrolled in the study. The median age at the time of corrective surgery was 74 days (range, 24-206 days). All of the BA cases received an operation by the time they were 60 days old. In the BA group (5 patients), the mean cyst size was 15 mm, the mean direct bilirubin (D-Bil) was 3.3 mg/dL, and the mean total bile acid (TBA) was 138.1 umol/L at 30 days of age, whereas in the CC group (5 patients), cyst size, D-Bil, and TBA were 40 mm, 0.9 mg/dL, and 46.9 umol/L, respectively. These differences between the 2 groups were statistically significant. All of the patients with CC successfully cleared their jaundice, whereas 4 patients with BA subsequently required liver transplantation for liver failure. In our study, all patients with BCM less than 21 mm, D-Bil greater than 2.5 mg/dL, and TBA greater than 111 umol/L in the neonatal period were diagnosed with BA. CONCLUSIONS: Our data suggested that patients with BCM smaller than 21 mm, D-Bil higher than 2.5 mg/dL, and TBA higher than 111 umol/L in the neonatal period were more likely to have BA than CC. This potential diagnosis should be surgically examined and corrected as soon as possible. PMID- 21034932 TI - Primary hepatic sarcomas in children--a single-center experience over 19 years. AB - BACKGROUND/PURPOSE: Primary hepatic sarcomas are rare and account for about 13% of primary hepatic neoplasms. There are few reported series of pediatric hepatic sarcomas, and the aim was to review our experience. METHODS: A retrospective analysis of cases managed from 1988 to 2007 by the pediatric liver unit in Birmingham, UK, was conducted. RESULTS: Nineteen children were identified. These presented with sudden abdominal pain (n = 6), obstructive jaundice (n = 3), incidental mass (n = 3), and chronic pain/distension (n = 3). Vascular involvement was identified in 3, and 6 had pulmonary metastases. Three patients had primary resection, and 3 only a biopsy. Thirteen had a biopsy followed by chemotherapy and resection. Surgery included extended hepatectomy (n = 11), hepatectomy (n = 3), and nonanatomical resections (n = 2). There was 1 major intraoperative complication. Median inpatient stay was 7 days. One biliary leak developed 4 weeks postoperatively. Five of the 16 patients who underwent resection of the primary tumor died. Eleven were alive at a median follow-up of 3 years. CONCLUSION: This is a challenging group of patients. Local control remains pivotal to successful treatment. Good results can be achieved in a specialist center with multidisciplinary approach. PMID- 21034933 TI - Embryonic Wnt gene expression in the nitrofen-induced hypoplastic lung using 3 dimensional imaging. AB - PURPOSE: Wnts have been reported to play a key role in the lung morphogenesis. We have previously reported that pulmonary gene expression of Wnt2 and Wnt7b is downregulated on day 15 of gestation in the nitrofen-induced congenital diaphragmatic hernia (CDH) model. However, the distribution pattern of gene expression of Wnts in the very early lung development remains unclear. Optical projection tomography (OPT) is a new technique for 3-dimensional imaging of small developing organs and gene distribution combined with whole-mount in situ hybridization. We designed this study to investigate the distribution pattern of Wnts gene expression in lung buds of nitrofen-induced CDH model using OPT. METHODS: Embryos from normal and nitrofen-treated dams were harvested on embryonic day 10 (E10), and divided into controls and nitrofen group, respectively. Whole-mount in situ hybridization to detect transcripts of Wnt2 and Wnt7b was performed, analyzed, and reconstructed using OPT. RESULTS: The expression of Wnt2 transcripts was detected in the lung bud mesenchyme and markedly diminished in nitrofen group compared to controls, whereas Wnt7b transcripts were expressed in the mesoderm of bronchi and the lung bud with no detectable difference between 2 groups. CONCLUSION: We provide evidence for the first time that Wnt2 expression is downregulated at lung bud stage in the nitrofen model. Optical projection tomography is potentially a useful approach to visualize both gene expression and morphology during very early stages of lung development. PMID- 21034934 TI - Limb ischemia after common femoral artery cannulation for venoarterial extracorporeal membrane oxygenation: an unresolved problem. AB - PURPOSE: Extracorporeal Life Support Organization Registry data confirm that the number of pediatric patients being supported by extracorporeal membrane oxygenation (ECMO) is increasing. To minimize the potential neurologic effects of carotid artery ligation, the common femoral artery (CFA) is frequently being used for arterial cannulation. The cannula has the potential for obstructing flow to the lower limb, thus increasing ischemia and possible limb loss. We present a single institution's experience with CFA cannulation for venoarterial (VA) ECMO and ask whether any precannulation variables correlate with the development of significant limb ischemia. METHODS: We reviewed all pediatric patients who were supported by VA ECMO via CFA cannulation from January 2000 to February 2010. Limb ischemia was the primary variable. The ischemia group was defined as the patients requiring an intervention because of the development of lower extremity ischemia. The patients in the no-ischemia group did not develop significant ischemia. Continuous variables were reported as medians with interquartile ranges and compared using Mann-Whitney U tests. Differences in categorical variables were assessed using chi2 testing (Fisher's Exact). Statistical significance was assumed at P < .05. RESULTS: Twenty-one patients (age, 2-22 years) were cannulated via the CFA for VA ECMO. Significant ischemia requiring intervention (ischemia group) occurred in 11 (52%) of 21. In comparing the 2 groups (ischemia vs no ischemia), no clinical variables predicted the development of ischemia (Table 1). In the ischemia group, 9 (81%) of 11 had a distal perfusion catheter (DPC) placed. Complications of DPC placement included one case of compartment syndrome requiring a fasciotomy and one patient requiring interval toe amputation. Of the 2 patients in the ischemia group who did not have a DPC placed, 1 required a vascular reconstruction of an injured superficial femoral artery and 1 underwent a below-the-knee amputation. Mortality was lower in the ischemia group (27% vs 60%). CONCLUSIONS: Limb ischemia remains a significant problem, as more than half of our patients developed it. The true incidence may not be known as a 60% mortality in the no-ischemia group could mask subsequent ischemia. Although children are at risk for developing limb ischemia/loss, no variable was predictive of the development of significant limb ischemia in our series. Because of the inability to predict who will develop limb ischemia, early routine placement of a DPC at the time of cannulation may be warranted. However, DPCs do not completely resolve issues around tissue loss and morbidity. Prevention of limb ischemia/loss because of CFA cannulation for VA ECMO continues to be a problem that could benefit from new strategies. PMID- 21034935 TI - Esophageal stethoscope: an old tool with a new role, detection of residual flow during video-assisted thoracoscopic patent ductus arteriosus closure. AB - BACKGROUND: Video-assisted thoracoscopic surgery (VATS) has emerged as an innovative and popular procedure for closure of a patent ductus arteriosus (PDA), but is associated with a minute rate of residual or recurrent duct patency. This study aims to analyze the efficacy of intraoperative esophageal stethoscopic monitoring in reducing the incidence of residual ductal flow during PDA clipping by VATS. METHODS: Between June 1997 and October 2009, we retrospectively assessed 2000 consecutive patients with PDA who underwent VATS. During the procedure, heart sounds were monitored by the anesthesiologist through an esophageal stethoscope. Changes in continuous cardiac murmurs were recorded before and after the PDA clipping and were confirmed to disappear completely. Color flow Doppler echocardiography was performed immediately before discharge, and patients were followed monthly for 3, 6, and 12 months and then annually to confirm the absence of residual or recurrent shunt. RESULTS: Mean age was 6.0 years (range, 1 month 35 years), mean weight was 11.1 kg (range, 6-65 kg), and mean PDA diameter was 5.5 mm (range, 3-9 mm). Ninety-two percent of patients showed no ductal flow after a single clipping. In the other 8% of patients, residual flow was detected intraoperatively after a single clipping, but was eliminated by the second clipping. Twelve patients (0.6%) presented with residual ductal flow immediately after the operation (detected by color Doppler echocardiography), which was eliminated by thoracotomy before discharge. All patients left the hospital with echocardiography documenting no evidence of residual PDA. At follow-up, the incidence of residual patency was 0.2% (4 of 2000). CONCLUSIONS: Our results demonstrate that the intraoperative esophageal stethoscope provides a remarkably effective technique for monitoring and evaluating PDA ligation by VATS, thus avoiding reintervention and the complications associated with residual ductal flow in most cases. PMID- 21034936 TI - Medical predictors for long-term behavioral and emotional outcomes in children and adolescents after invasive treatment of congenital heart disease. AB - BACKGROUND: The aim of the study was to test the following: (1) the predictive value of medical variables for long-term parent-reported behavioral and emotional problems in children and adolescents who underwent invasive treatment of congenital heart disease in infancy and (2) the relationship between parental psychological distress and parental reports on problems in children. METHODS: The Child Behavior Checklist was used to investigate to what extent behavioral and emotional problems in 7- to 17-year-old children with congenital heart disease can be predicted by the following: (1) medical history, (2) therapeutic intervention and direct postinterventional course, (3) long-term medical course, (4) present contact with physicians, and (5) present medical status. The General Health Questionnaire was used to assess parental distress (especially anxiety). RESULTS: Higher Child Behavior Checklist total problems scores were predicted by cardiac medication before therapeutic intervention. Palliative intervention (Rashkind procedure) before therapeutic intervention was associated with more favorable scores on total problems and externalizing. Long-term maternal distress was significantly related to parent-reported problems in children. CONCLUSION: Long-term behavioral and emotional outcomes are only marginally predicted by medical variables. In counseling of children with congenital heart disease and their parents, attention should be paid to long-term maternal distress that has an influence on parent-reported problems in children. PMID- 21034937 TI - Influence of adrenal hormones in the occurrence and prevention of stress ulcers. AB - PURPOSE: The aim of the study was to examine whether endogenous cortisol and adrenalin have a role in the formation of stress ulcers in intact and adrenalectomized rats. METHODS: The study was composed of 4 experiments: ulcerated areas in stomachs of adrenalectomized and intact rats were measured, adrenaline (100 MUg/kg) and prednisolone (5 mg/kg) were injected intraperitoneally in adrenalectomized rats, metyrapone (200 mg/kg) and metyrosine (200 mg/kg) were administered to intact rats, and metyrapone (200 mg/kg) and metyrosine (200 mg/kg) were administered orally with yohimbine (10 mg/kg) and yohimbine (10 mg/kg) alone were administered to intact rats. After 24-hour restraint stress, ulcerated areas were measured. RESULTS: In the stomach of intact rats, the degree of stress ulcer was 7.25 times more severe than that noted in adrenalectomized rats. Furthermore, stress ulcers in adrenalectomized rats that received adrenaline or prednisolone only were fewer and less severe than rats receiving both adrenaline and prednisolone. CONCLUSIONS: Simultaneous administration of adrenaline and prednisolone did not prevent the formation of stress ulcers. However, either of these hormones alone (adrenaline or prednisolone), in the absence of the other, repressed the formation of stress ulcers. This antiulcer activity may be related to alpha2-adrenergic receptor activity. PMID- 21034938 TI - Impact of tumor viability at second-look procedures performed before completing treatment on the Intergroup Rhabdomyosarcoma Study Group protocol IRS-IV, 1991 1997: a report from the children's oncology group. AB - PURPOSES: The aims of the study were to compare results of clinical/radiographic studies before second-look procedures (SLP) with SLP specimens from patients with gross residual sarcoma at diagnosis and to relate tumor viability to outcome. PATIENTS: Seventy-three patients underwent SLP before completing chemotherapy, with (n = 59) or without (n = 14) radiotherapy. Tumor sites were bladder/prostate (n = 27), head/orbit/parameningeal (n = 22), extremity/trunk (n = 14), and retroperitoneum/pelvis (n = 10). RESULTS: Of 14 patients, 1 (7%) with clinical/radiographic complete response (CR) had viable tumor. Of 59 patients, 35 (59%) without CR had viable tumor. Five-year failure-free survival (FFS) rates were 81% in 37 patients without viable tumor and 53% in 36 patients with viable tumor (Cox proportional hazards adjusted P = .05). Five-year FFS rates were 67% in 15 patients with clear margins and 43% in 21 patients with tumor-involved margins (n = 18) or viable gross tumor (n = 3) (Cox proportional hazards adjusted P = .04). Five-year survival was 78% to 79% among 73 patients with and 333 patients without SLP during treatment. CONCLUSIONS: Second-look procedures can show whether viable tumor is present and may be beneficial in selected patients with rhabdomyosarcoma. Disappearance of tumor (CR) usually correlated with no viable tumor at SLP. However, 41% of patients without CR had no viable tumor. Those without viable tumor had increased FFS but not survival compared to those with viable tumor. PMID- 21034939 TI - Protective effects of clarithromycin in rats with hypoxia/reoxygenation-induced intestinal injury. AB - BACKGROUND: This study was designed to determine the role of oxidative stress, nitric oxide (NO), and glutathione-related antioxidant enzymes in rat pups with hypoxia/reoxygenation (H/R)-induced bowel injury and to evaluate the potential benefits of prophylactic clarithromycin. METHODS: One-day-old Wistar albino rat pups (N = 21) were randomly divided into 3 groups: group I (control), group II (exposed to H/R), and group III (clarithromycin + H/R). Clarithromycin was administered (40 mg/kg) subcutaneously to group III for 3 days. On the fourth day, all rats except controls were exposed to H/R and were killed at 6 hours after H/R. Histopathologic injury scores (HIS), malonyldialdehyde, glutathione (GSH), glutathione-peroxidase (GSH-Px) activities, and NO levels were measured on intestinal samples. RESULTS: Whereas there was no difference for malonyldialdehyde levels among groups, HIS and NO levels were higher in group II than groups I and III (P < .05). However, GSH and GSH-Px activities were lower in group II than groups I and III (P < .05). Clarithromycin significantly increased GSH and GSH-Px activities and reduced HIS and NO levels in group III. CONCLUSION: This study showed that oxidative stress and NO contributed to the pathogenesis of H/R-induced bowel injury and that clarithromycin had a protective effect on bowel injury owing to anti-inflammatory and antioxidant effects. PMID- 21034940 TI - Management of recurrent intussusception: nonoperative or operative reduction? AB - PURPOSE: The aim of this study was to determine how to manage children with recurrence of intussusception. METHODS: Medical records of patients treated for intussusception from 1976 to 2008 at the Queen Sirikit National Institute of Child Health were reviewed. Information on patients who developed recurrent intussusception was extracted to study patterns of recurrent attack and suitable management procedures. The statistical differences were analyzed by the chi2 and the Student t test, with a P value < .05 considered significant. RESULTS: During the study period, 1340 patients were treated for 1448 episodes of intussusceptions, with an average of 40 cases per year. There were 108 episodes of recurrent intussusception in 75 patients (45 males and 30 females). The overall recurrence rate was 8%. Patient age at the first episode ranged from 3 months to 12 years (average, 14.9 months). The time interval before each recurrence ranged from 1 day to 3.2 years (average, 7.8 months). The number of recurrences ranged from 1 to 5 attacks. Recurrent intussusception occurred in 35 (15.8%) of 222 children following successful hydrostatic barium enema (BE) reduction and in 55 (11.4%) of 482 after successful pneumatic or air enema (AE) reduction. There was no statistical difference between the recurrence rates after the 2 nonoperative procedures (P = .08). Recurrent intussusception developed in 14 (3.0%) of 457 patients after operative manual reduction. Recurrence was not observed after intestinal resection for initial irreducible intussusception in 175 patients. The remaining 4 recurrent episodes occurred after spontaneous reduction. Of the 108 episodes of recurrence, BE and AE reductions were successful in 25 (96.2%) of 26 attempts and in 57 (92%) of 62 attempts, respectively. Seven patients had their first episode of intussusception treated surgically. All 7 when they recurred were successfully treated with either BE or AE reduction. Operative intervention was needed in 23 episodes of recurrent intussusception; 18 were reduced manually, and 5 required intestinal resection. Overall, 7 (9.3%) of the 75 recurrences had a pathologic lead point: colonic polyps in 4 cases and Meckel diverticulum in 3 cases. There were no deaths among the 75 patients with recurrent intussusception. CONCLUSIONS: Recurrent intussusception should be initially treated by nonoperative reduction. Laparotomy is needed in cases with failure of BE or AE reduction, in cases with suspicion of a pathologic lead point, and in selected cases with several episodes of recurrence. The treatment of recurrent intussusception, in general, should be similar to that of primary intussusception. PMID- 21034941 TI - Antibiotics and appendicitis in the pediatric population: an American Pediatric Surgical Association Outcomes and Clinical Trials Committee systematic review. AB - OBJECTIVE: The aim of the study was to review evidence-based data regarding the use of antibiotics for the treatment of appendicitis in children. DATA SOURCE: Data were obtained from PubMed, MEDLINE, and citation review. STUDY SELECTION: We conducted a literature search using "appendicitis" combined with "antibiotics" with children as the target patient population. Studies were selected based on relevance for the following questions: (1) What perioperative antibiotics should be used for pediatric patients with nonperforated appendicitis? (2) For patients with perforated appendicitis treated with appendectomy: a. What perioperative intravenous antibiotics should be used? b. How long should perioperative intravenous antibiotics be used? c. Should oral antibiotics be used? (3) For patients with perforated appendicitis treated with initial nonoperative management, what antibiotics should be used in the initial management? RESULTS: Children with nonperforated appendicitis should receive preoperative, broad spectrum antibiotics. In children with perforated appendicitis who had undergone appendectomy, intravenous antibiotic duration should be based on clinical criteria. Furthermore, broad-spectrum, single, or double agent therapy is as equally efficacious as but is more cost-effective than triple agent therapy. If intravenous antibiotics are administered for less than 5 days, oral antibiotics should be administered for a total antibiotic course of 7 days. For children with perforated appendicitis who did not initially undergo an appendectomy, the duration of broad-spectrum, intravenous antibiotics should be based on clinical symptoms. CONCLUSIONS: Current evidence supports the use of guidelines as described above for antibiotic therapy in children with acute and perforated appendicitis. PMID- 21034942 TI - Single-incision laparoscopic appendectomy vs multiport laparoscopic appendectomy in children: a retrospective comparison. AB - BACKGROUND: Minimally invasive surgery is commonly used to treat appendicitis. Single-incision laparoscopic surgery is an attractive modality to treat a commonly occurring problem with the advantage of minimal or possibly no scarring. We sought to compare our results of single-incision laparoscopic appendectomy (SILA) with those of patients undergoing traditional multiport laparoscopic appendectomy (MPLA). PATIENTS AND METHODS: A retrospective review of all patients who underwent a minimally invasive appendectomy from September 2009 to February 2010 was performed. The patients were divided into 2 groups based on if they had a SILA or a traditional MPLA. Outcomes including demographics, diagnosis, operative time, length of stay, narcotic usage, and complications were evaluated. RESULTS: A total of 110 patients underwent appendectomy. There were 50 patients who underwent SILA and 46 patients who underwent MPLA. Fourteen patients with perforated appendicitis were excluded. Mean age (11.1 vs 11.7 years, P = .43), weight (43.3 vs 50.9 kg, P = .27), and length of stay (1.1 vs 1.2 days, P = .56) were comparable between both groups. Operative time for SILA was slightly longer (33.8 vs 26.8 minutes, P = .01). Overall intravenous narcotic use was lower in the SILA group (0.9 vs 1.4 doses, P = .01), but there was no difference in the patients who also received ketorolac (0.8 vs 1.0 doses, P = .6). Four patients in the SILA group developed superficial wound infections and 1 patient in the SILA group was admitted for postoperative abscess. CONCLUSIONS: Single-incision laparoscopic appendectomy is safe and effective in the pediatric population. Further studies should be performed to determine the impact on operative time and postoperative narcotic requirements. PMID- 21034943 TI - Endoscopic transaxillary approach for congenital muscular torticollis. AB - BACKGROUND: Surgical correction of the congenital muscular torticollis (CMT) is recommended for patients with unsuccessful conservative treatment. Open operative techniques all leave noticeable scars. We proposed a modified endoscopic 1-trocar transaxillary and neck microincision approach for the treatment of CMT. METHODS: Endoscopic release of the sternocleidomastoid (SCM) muscle was performed in 45 infants and children aged 6 months to 15 years. One 5-mm incision was made in the anterior axillary fold, and a subcutaneous tunnel over the clavicular and sternal heads of the SCM muscle was made. A subcutaneous space was established by CO2 inflation at a pressure of 8 mm Hg and then endoscopically using a 5-mm endoscope. Two additional 1.5- to 2-mm supraclavicular mini-incisions were made beside the SCM muscle for the introduction of miniforceps and electrocautery, respectively. The sternal and clavicular attachments were dissected and divided by electrocautery. Clinical evaluation was performed using the Lee scoring system. RESULTS: The operation was successfully completed endoscopically in all 45 children. The mean operative time was 40 minutes. No injuries of major blood vessels or nerves were encountered. A small bleed was noted in 1 child owing to reoperation. Follow-up for 6 months to 3 years in 42 patients showed complete muscular release and satisfactory cosmetic appearance with no recurrence. The results were classified as excellent in 88.1% (37/42), good in 9.5% (4/42), fair in 2.4% (1/42), and poor in 0 using the Lee scoring system. The neck scars were not visible 1 month after the procedure. CONCLUSIONS: The subcutaneous endoscopic transaxillary and micro-neck incision approach for the treatment of CMT is a safe, practical procedure that provides good functional and cosmetic outcomes without vascular or neural injury. PMID- 21034944 TI - Embryonic development of the internal anal sphincter in rats with anorectal malformations. AB - BACKGROUND/PURPOSE: The embryogenesis of the internal anal sphincter (IAS) in anorectal malformations (ARMs) remains unclear. This study aimed to investigate the development of the smooth muscle in the terminus of the digestive tract in normal and abnormal rats. METHODS: Rat embryos with ARMs were generated by administration of ethylenethiourea to pregnant rats. The normal rat embryos and embryos with ARMs from E13.5 to E21 were serially sectioned in the sagittal plane and stained immunohistochemically using specific antibody to alpha-smooth muscle actin (SMA). Temporospatial study was carried out on circular muscle of the distal portion of the hindgut. RESULTS: alpha-Smooth muscle actin immunolabeling cells could not be observed in the hindgut on E13.5, E14, and E14.5. On E15, there were alpha-SMA immunolabeling circular muscle cells in the hindgut; and the distal portion of the circular muscle was not thickened in the normal and ARMs rats. From E16 onward, the smooth muscle with slight dilated terminus, which was characterized by the features of IAS, could be noted in the primitive anorectum. In the normal group, the circular muscle in the distal portion of the hindgut thickened slightly and became the musculature with shutter-like bundles. In the ARMs group, the alpha-SMA immunolabeling myogenic precursors of the smooth muscle could be observed in the primitive anorectum as well. The musculature was similar to that in the normal group. On E15 and E16, there was no significant difference in the development of the circular muscle in the 2 groups. Moreover, the terminus of the circular muscle in the hindgut did not reach the orificium fistulae in ARMs rats. From E17 onward, in ARMs rats, the funnel-shaped distal hindgut communicated the genitourinary tract with a narrow fistula; the dilated musculature at this portion thinned gradually and formed an acute angled extremity in the ARMs group rather than formed blunt extremity in the normal group; the terminus circular muscle in the dorsal hindgut reached the orificium fistulae. During the following gestational days, the circular muscle of the hindgut in both normal and ARMs rats continued its own tendency. CONCLUSION: The IAS primordium started to appear at the terminus of the hindgut on E15 in the 2 groups. The IAS in the ARMs group failed to develop as well as that in the normal group. The IAS dysplasia occurred in the late embryonic development (E17-E21). PMID- 21034945 TI - Protective effect of tadalafil on ischemia/reperfusion injury of rat ovary. AB - BACKGROUND/PURPOSE: The aim of the study was to evaluate the effects of tadalafil (TDF) on ischemia/reperfusion (I/R) injury in rat ovaries. METHODS: Thirty-five female Sprague-Dawley rats were randomly divided into 5 groups (n = 7): sham (S), I/R1, I/R2, TDF1, and TDF2. In the I/R1 and TDF1 groups, 3-hour ischemia was followed by 12-hour reperfusion; and in the I/R2 and TDF2 groups, 3-hour ischemia was followed by 24-hour reperfusion. In the TDF groups, 30 minutes before reperfusion, a single dose of 5 mg/kg TDF was administered intraperitoneally. The ovarian tissue levels of malondialdehyde and nitric oxide (NO), and the activities of superoxide dismutase and catalase were measured biochemically. Tissue damage to ovarian tissue was scored by histopathologic examination. RESULTS: The tissue malondialdehyde levels were significantly higher and the catalase and superoxide dismutase activities were significantly lower in the I/R groups compared with the S and TDF groups (P < .05). The NO levels were significantly higher in the TDF1 group than the S and I/R1 groups (P < .05). Although the NO levels were increased in the TDF2 group compared with the I/R2 group, the difference was not significant. Ovarian tissue damage scores of the I/R groups were significantly higher than those of the S group (P < .05). Treatment with TDF significantly decreased the ovarian tissue damage scores in the TDF groups compared with the I/R groups (P < .05). CONCLUSIONS: Tadalafil is effective in preventing tissue damage induced by I/R in rat ovaries. PMID- 21034946 TI - Laparoscopic hernia repair in infancy and childhood: evaluation of 2 different techniques. AB - PURPOSE: Laparoscopic hernia repair in infancy and childhood is still debatable. There are many techniques available for laparoscopic hernia repair in children. The objective of this study was to compare intracorporeal suturing and knotting with extracorporeal knotting for repair of congenital inguinal hernia in infants and children about operative time, recurrence rate, hydrocele formation, and postoperative cosmetic results. A randomized controlled study was carried out in the Pediatric Surgery Unit of Al-Azhar University Hospitals (Cairo, Egypt) over a 3-year period. PATIENTS AND METHODS: One hundred fifty patients with congenital inguinal hernia were randomized into 2 equal groups (n = 75). Group A was subjected to intracorporeal purse string suture around the internal inguinal ring (IIR) using 2 needle holders. Group B was subjected to insertion of purse string suture around IIR using a Reverdin needle (RN) and extracorporeal knotting. Inclusion criteria included bilateral inguinal hernia, recurrent hernia, hernia in obese children, incarcerated hernia, and ipsilateral hernia with questionable hernia on the contralateral side. Exclusion criteria included unilateral inguinal hernia and hernia with undescended testicles. The main outcome measurements were operative time, length of hospital stay, postoperative hydrocele formation, recurrence rate, and cosmetic results. RESULTS: There were no significant differences about age, sex, and mode of presentation between both groups. All cases were completed successfully without conversion. There were significant statistical differences in the operative time, recurrence rate, and cosmetic results between the studied groups, whereas there were no significant statistical differences in the hospital stay and postoperative hydrocele formation. CONCLUSION: Laparoscopic hernia repair by RN is an effective method of hernia repair in infants and children. It resulted in a marked reduction of operative time and excellent cosmetic results with low recurrence. PMID- 21034947 TI - Urethral hydrodistension for management of urethral hypoplasia in prune belly syndrome: long-term results. AB - PURPOSE: The aim of the study was to evaluate the efficacy and safety of urethral hydrodistension for management of urethral hypoplasia in prune belly syndrome (PBS). METHODS: During a 10-year period, 7 infants with PBS and urethral hypoplasia presented either with open urachus or surgically created urinary diversion referred to our hospital. Five milliliters of normal saline was pushed via a 22-gauge plastic angiocatheter into the urethra with simultaneous finger pressure on the perineum to occlude the proximal urethra that was repeated with higher volumes of the solution (up to 20 mL). The procedure was continued until a 6F or 8F feeding tube catheter confirmed the urethral patency. Hydrodistension was repeated in 3-month intervals till complete patency was confirmed by imaging. RESULTS: Median age of the infants was 6 (1-8) months. All urethral hydrodistension were successful after 1 to 3 sessions. Follow-up imaging studies showed significant improvement in all patients except one. Natural and surgically created urinary diversions were closed in 6 infants. CONCLUSIONS: The hydrodistension create an equal and constant pressure into the urethral wall without any urethral damage. This technique can be considered along with the other available methods for management of urethral hypoplasia in selected cases of PBS. PMID- 21034948 TI - Surgical complications of posterior urethral valve ablation: 20 years experience. AB - PURPOSE: The aim of the study was to report the surgical complications that may occur during or after primary ablation of posterior urethral valve (PUV) in a large number of cases treated using different modalities. MATERIALS AND METHODS: We retrospectively reviewed a database of 291 patients with PUV treated by primary valve ablation from 2 separate centers between 1987 and 2006. Primary valve ablation was performed in all patients regardless of serum creatinine level or upper tract configuration. A hot loop resectoscope was used in 122 patients, cold knife urethrotome in 108, a hook diathermy electrode in 18, a diathermy coagulation bugbee electrode in 20, whereas stripping using a Fogarty catheter was performed in 23. RESULTS: The follow-up duration ranged from 1.5 to 20 years (median, 6.5). Early postoperative complications occurred in 22 patients (7.5%). The most common complication was urinary retention in 16 patients (5.5%). Urinary extravasations occurred in 3 cases, significant hematuria from urethral bleeding occurred in 2, and obstructive anuria developed in 1 patient. Most of cases were treated conservatively. Urethral strictures developed in 6 patients (2%) mainly after endoscopic loop resection (4/6). All were treated by visual internal urethrotomy and urethral dilatation with successful results without the need of open urethroplasty. CONCLUSIONS: Primary valve ablation seems to be safe and is associated with low rate of postoperative complications. All the complications could be treated conservatively. Urethral stricture may occur after valve ablation in a minority of cases and can be successfully treated endoscopically. Loop resection is associated with more strictures. PMID- 21034949 TI - American Pediatric Surgical Association New Technology Committee review on video assisted thoracoscopic surgery for childhood cancer. AB - BACKGROUND/PURPOSE: Although the use of minimally invasive surgical (MIS) techniques for children with cancer is being practiced by some, its role remains unclearly defined. The purpose of this review was to describe the current literature on MIS for thoracic and mediastinal lesions in children. METHODS: We performed a literature search for English studies that evaluated MIS techniques for biopsy or resection in children with suspected or established cancer. Only studies with greater than 20 patients were included in the review. RESULTS: Ten studies were included for review. Each represented institutional retrospective reviews of experience. Seven were single-institution studies, and 3 were multi institutional. There were no prospective nor randomized identified. CONCLUSIONS: Based on primarily retrospective and observational data, the use of MIS for children with cancer who have pulmonary and mediastinal lesions seems to be effective and safe. Ideally, prospective studies are needed to evaluate this further. PMID- 21034950 TI - Stomal prolapse in children with chronic intestinal pseudoobstruction: a frequent complication? AB - AIM: The aim of the study was to evaluate the morbidity rate of stoma in children diagnosed with chronic intestinal pseudoobstruction (CIPO) and try to determine risk factors. MATERIAL AND METHODS: Twenty-two children (65%) of 34 referred to our center between 1988 and 2008 had a stoma. They were compared with 22 other children referred for another pathology necessitating a stoma. RESULTS: The incidence of stomal prolapse in CIPO children was 45% vs 9% in non-CIPO children (P = .01). Prolapse occurred between the first postoperative day and the 10th postoperative month, with a median of 2 months. Surgical management was required in 60%, with an intestinal necrosis rate of 20% leading to intestinal resection. No mortality was noted. No risk factors favoring prolapse in CIPO children were identified. CONCLUSION: Children with CIPO have a high rate of stomal prolapse with an increased risk of intestinal necrosis. Careful management of the stoma is necessary to avoid the risk of intestinal resection, which may aggravate the underlying intestinal disorder. PMID- 21034951 TI - Use of the Hunt-Lawrence pouch in congenital microgastria--a report of 2 cases. AB - Congenital microgastria is an uncommon condition and often associated with other abnormalities. We present 2 patients with congenital microgastria who underwent repair with a Hunt-Lawrence pouch. PMID- 21034952 TI - Primary endobronchial schwannoma. AB - Primary intrabronchial neurilemmas, also called schwannomas, are extremely rare tumors that originate from Schwann cells. We report a case of intrabronchial schwannoma arising in the left main bronchus in an 8-year-old child. The diagnosis was made by bronchofiberscopic biopsy. Although the tumor was benign, the patient was subjected to left pneumonectomy because of destruction of the pulmonary parenchyma distal to the obstruction. The diagnosis of intrabronchial schwannoma was supported pathologically with characteristic findings on Antoni A and Antoni B areas. This case is unique in that it is the youngest case in the literature. PMID- 21034953 TI - Serous borderline tumor of the fallopian tube in a patient with Klippel-Trenaunay syndrome. AB - We describe a case of a 3-year-old girl with Klippel-Trenaunay syndrome who presented with an enlarging abdominal mass caused by a serous borderline tumor of the fallopian tube. This case is notable for the rarity of this neoplasm in a premenarchal patient as well as the association with this syndrome. We briefly review these entities and the significance of malignancy in Klippel-Trenaunay syndrome. PMID- 21034954 TI - Primary hydatid cyst of the rib mimicking chest wall tumor: a case report. AB - Hydatidosis, caused by Echinococcus granulosus, is still an endemic parasitic disease in the Mediterranean area, South America, North Africa, and Australia. The most common anatomic location of hydatid disease is the liver, followed by the lung. Hydatidosis is located in the bones in 0.5% to 2% of all cases. A hydatid cyst can be seen in any part of the body. However, primary hydatid cyst of the rib in childhood is exceedingly rare. We report the first case of a pediatric hydatid cyst of the rib mimicking chest wall tumor. PMID- 21034955 TI - Costal osteochondroma causing pneumothorax in an adolescent: a case report and review of the literature. AB - Costal osteochondroma is a rare but important condition to recognize because of the possibility of serious consequences if not diagnosed and treated promptly. Patients can present with numerous complications, including hemothorax, pneumothorax, nervous or vascular impingement, and fracture. We report the case of a 17-year-old adolescent boy who presented to the pediatrician with intermittent shortness of breath and pleuritic chest pain. A chest x-ray demonstrated a left-sided pneumothorax and triangular opacity in the left chest. A computed tomographic scan of the chest revealed the cause to be a costal exostosis of the anterior fifth rib. The lesion was excised using video-assisted thoracoscopic surgery, which has become an increasingly popular method for treating these lesions, causing significantly less morbidity and allowing for a faster recovery than a major thoracotomy. PMID- 21034956 TI - Endoscopic management of a type IV syringocele causing massive perirenal urinoma in an infant. AB - The finding of a urinoma in the fetal and neonatal period is almost always related to an obstruction distal to the collection itself. Syringocele is a congenital or acquired dilation of a bulbourethral Cowper's gland. An exceedingly rare case of neonatal anterior urethral obstruction caused by a syringocele and manifesting itself with a dramatic clinical onset is presented. Clinical and radiologic findings are discussed and minimally invasive therapeutic strategies emphasized. PMID- 21034957 TI - Mucinous adenocarcinoma of the lung in association with congenital pulmonary airway malformation. AB - Congenital pulmonary airway malformation (CPAM) is a rare developmental abnormality of the lung that has been associated with the presence of rhabdomyosarcoma, pleuropulmonary blastoma, and most commonly bronchioalveolar carcinoma (BAC) of the lung. Here, we report the case of an 8-year-old patient who developed KRAS mutation positive stage IV mucinous adenocarcinoma of the lung in association with CPAM. This case reflects the previously recognized progression of CPAM to malignancy and suggests that BAC arising in CPAM may take a more aggressive course than previously recognized. PMID- 21034958 TI - Traumatic hemipelvectomy in children: report on 2 survivors with urological involvement. AB - Traumatic hemipelvectomy through the sacroiliac joint is a devastating injury, mainly because of motor vehicle accidents. Recent improvements in prehospital trauma care have increased the chances of survival for victims. Besides amputation of the lower limb, associated complications usually involve digestive and urological systems. We report on 2 pediatric patients from 2 different European countries. PATIENT 1: A 9-year-old boy suffered uprooting of his left lower limb, laceration of the rectum and anal sphincter, as well as an injury to distal urethra with partial loss of cavernous bodies. Initial management included a colostomy and an essay of contention by means of a polypropylene prosthesis that had to be removed in the following months. After several attempts at urethral reconstruction, he underwent a Mitrofanoff derivation. PATIENT 2: An 18 month-old girl lost her left lower limb and suffered severe lacerations of bladder and rectum. Among other measures, management included a colostomy, a skin graft, and 2 attempts at reconstruction of her bladder neck, including a modified Casale procedure (cecum and ileocecal appendix were in a high position that made a Mitrofanoff derivation impossible) and a Malone procedure. To the authors' knowledge, she would be the youngest reported survivor of this kind of injury. PMID- 21034959 TI - Hydrosalpinx in a patient with complex genitourinary malformation. AB - We describe an adolescent female patient born with a complex genitourinary malformation including bilateral duplex system and duplication of the mullerian structures (bicornuate uterus and septate vagina). She presented with a symptomatic hydrosalpinx. The typical imaging of this condition is described along with the issues associated with the differential diagnosis in this complex scenario. The diagnosis of hydrosaplinx should be suspected in patients with complex genitourinary malformations and a pelvic fluid collection. Associated genital and renal anomalies are noted in 30% of cases. PMID- 21034960 TI - Ectopic extralobar pulmonary sequestrations in children: interest of the laparoscopic approach. AB - BACKGROUND: Extralobar pulmonary sequestrations (EPS) are a rare benign congenital bronchopulmonary foregut malformation. Complete resection is necessary to confirm the diagnosis with histopathologic examination. The aim of this study was to describe the laparoscopic minimally invasive surgery (MIS) for a small series of ectopic EPS in small children and to show its feasibility and safety. METHODS: From January 2001 to December 2008, 12 cases of EPS were prenatally diagnosed and retrospectively reviewed. From this group, we isolated 6 children with ectopic EPS. Ages ranged from 15 days to 14 months. Three infants were symptomatic, and the others showed persistence of the lesion with parental anxiety. All prenatal diagnoses were confirmed by postnatal Doppler ultrasound and intravascular contrast computed tomography scan with 3-dimensional reconstructions. Postnatally, all were ectopic lesions: 3 were hiatal and intradiaphragmatic, 3 infradiaphragmatic and left paramedian. Laparoscopic MIS consisted of 4 small trocars and low-pressure pneumoperitoneum. We carried out a retroesophageal dissection in 4 cases, an elective control of systemic vessels, and a removal of the EPS with histologic study. RESULTS: We performed 5 procedures laparoscopically and 1 thoracoscopically. There were 2 abdominal conversions. Nevertheless, no intraoperative or immediate postoperative complications occurred. Hospital stay ranged from 1 to 5 days (mean, 2.7 days). The diagnosis of pure pulmonary sequestration with feeding vessels in 5 cases was confirmed by histopathology. Follow-up ranged from 13 to 84 months (mean, 43 months). Late complications were benign. CONCLUSIONS: Laparoscopic MIS for ectopic EPS in small children is a feasible and safe technique. The great magnification provided by the endoscopic procedure allows for the search of associated congenital anomalies, meticulous retroesophageal dissection, and control of the systemic vessels. Resection provides definitive diagnosis and treatment, and confers the benefits of a minimal access technique. PMID- 21034961 TI - Ventriculovascular shunts via the femoral vein: a temporary feasible alternative in pediatric hydrocephalus. AB - Ventriculovascular shunts via the femoral vein have been described as a feasible alternative for cerebrospinal fluid diversion in those complex cases of hydrocephalus in which other accesses are discarded. However, experience is short. To our knowledge, only 4 cases have been reported in the literature to date. We report 2 cases of hydrocephalic children who were developed several complications related to ventriculoperitoneal and ventriculoatrial shunts and who successfully managed by means of ventriculovascular shunts via the femoral vein. Both patients underwent vascular catheter placement through a venotomy performed in the common femoral vein. Catheter advance was controlled under fluoroscopic guidance. Distal catheters were joined by means of a straight connector, and a loop was accommodated in a subcutaneous pocket in the inguinal region to avoid future complications. The femoral vein is a successful alternative approach for distal catheter placement in ventriculovascular shunts when other accesses are ruled out. PMID- 21034962 TI - Pediatric applied trauma research network: a call to action. PMID- 21034963 TI - Postnatal intestinal ischemia in a patient with gastroschisis: a sinister problem of home delivery and improper transportation. PMID- 21034964 TI - Insights into the evolution of lymphomas induced by Epstein-Barr virus. AB - Epstein-Barr virus (EBV) encodes a wealth of oncogenic instructions, including the abilities to drive a resting normal B cell to proliferate and to override apoptotic stimuli. EBV is found in almost all types of lymphomas at varying frequencies. However, the particular viral genes expressed differ considerably among tumors. We have examined the role of EBV in several lymphomas by conditionally evicting the extrachromosomal viral genome from tumor cells in vitro and have found a graded dependence on the virus. Tumor cells that express all the known latent viral genes have been found to depend on the virus to drive proliferation and to block apoptosis at least in part by repressing the proapoptotic protein Bim. Other tumor cells, which express fewer viral genes, also depend on the virus to block apoptosis, but rely on the virus to promote but not to drive proliferation. Lastly, tumor cells with the fewest viral genes expressed have been found to require EBV to prevent the inefficient induction of a Bim-independent apoptosis. We present a model for the evolution of EBV-induced lymphomas in which tumors are initially "addicted" to the virus for almost all oncogenic functions. These tumors are targets for the immune system because they express multiple immunogenic viral proteins. Therefore, EBV-induced tumors are under selective pressure to acquire cellular mutations that can replace viral functions. We posit that the heterogeneity in viral gene expression among different EBV-associated lymphomas reflects a dynamic process by which tumors evolve to be less dependent on the virus. PMID- 21034965 TI - Recent advances in the research of hepatitis B virus-related hepatocellular carcinoma: epidemiologic and molecular biological aspects. AB - Hepatocellular carcinoma (HCC) is one of the commonest cancers worldwide, and more than half of HCC patients are attributable to persistent hepatitis B virus (HBV) infections. The best and cheapest way to prevent HBV-related HCC is the implementation of universal hepatitis B vaccination program, by which the incidence rates of childhood HCC have been reduced in several countries, including Taiwan. However, there are still hundreds of millions of HBV carriers in the world that remain a global health challenge. In the past decade, several hepatitis B viral factors such as serum HBV DNA level, genotype, and naturally occurring mutants have already been identified to influence liver disease progression and HCC development in HBV carriers. Several easy-to-use scoring systems based on clinical and viral characteristics are developed to predict HCC risk in HBV carriers and may facilitate the communication between practicing physicians and patients in clinical practice. In addition, the role of nonviral factors in HBV-related HCC has also been increasingly recognized. On the basis of these emerging data, it is recommended that HBV carriers should be screened and monitored to identify those who have a higher risk of liver disease progression and require antiviral treatments. Regarding the molecular carcinogenesis of HCC development, despite some progress in the research of cell biology of HCC in the past decade, aberrant pathways involved in maintaining HCC phenotypes have not been completely elucidated yet. In the future, through comprehensive and integrated approaches to analyze the genomes of human HCC, novel target genes or pathways critically involved in hepatocarcinogenesis may hopefully be identified. PMID- 21034966 TI - The ATM-Chk2 and ATR-Chk1 pathways in DNA damage signaling and cancer. AB - DNA damage is a key factor both in the evolution and treatment of cancer. Genomic instability is a common feature of cancer cells, fuelling accumulation of oncogenic mutations, while radiation and diverse genotoxic agents remain important, if imperfect, therapeutic modalities. Cellular responses to DNA damage are coordinated primarily by two distinct kinase signaling cascades, the ATM-Chk2 and ATR-Chk1 pathways, which are activated by DNA double-strand breaks (DSBs) and single-stranded DNA respectively. Historically, these pathways were thought to act in parallel with overlapping functions; however, more recently it has become apparent that their relationship is more complex. In response to DSBs, ATM is required both for ATR-Chk1 activation and to initiate DNA repair via homologous recombination (HRR) by promoting formation of single-stranded DNA at sites of damage through nucleolytic resection. Interestingly, cells and organisms survive with mutations in ATM or other components required for HRR, such as BRCA1 and BRCA2, but at the cost of genomic instability and cancer predisposition. By contrast, the ATR-Chk1 pathway is the principal direct effector of the DNA damage and replication checkpoints and, as such, is essential for the survival of many, although not all, cell types. Remarkably, deficiency for HRR in BRCA1- and BRCA2 deficient tumors confers sensitivity to cisplatin and inhibitors of poly(ADP ribose) polymerase (PARP), an enzyme required for repair of endogenous DNA damage. In addition, suppressing DNA damage and replication checkpoint responses by inhibiting Chk1 can enhance tumor cell killing by diverse genotoxic agents. Here, we review current understanding of the organization and functions of the ATM-Chk2 and ATR-Chk1 pathways and the prospects for targeting DNA damage signaling processes for therapeutic purposes. PMID- 21034967 TI - microRNAs in cancer: from bench to bedside. AB - microRNAs (miRNAs) are master regulators of gene expression. By degrading or blocking translation of messenger RNA targets, these noncoding RNAs can regulate the expression of more than half of all protein-coding genes in mammalian genomes. Aberrant miRNA expression is well characterized in cancer progression and has prognostic implications for cancer in general. Over the past several years, accumulating evidence has demonstrated that genomic alterations in miRNA genes are correlated with all aspects of cancer biology. In this review, we describe the effects of miRNA deregulation in the cellular pathways that lead to the progressive conversion of normal cells into cancer cells as well as in cancer diagnosis and therapy in humans. PMID- 21034968 TI - Advances in Immunology. Mucosal immunity. Preface. PMID- 21034969 TI - Functional biology of the IL-22-IL-22R pathway in regulating immunity and inflammation at barrier surfaces. AB - Expression of interleukin (IL)-22, a member of the IL-10 cytokine family, has recently been reported in a number of human diseases, including mucosal associated infections and inflammatory disorders of the intestine, skin, and joints. Both T cells and an emerging category of innate lymphoid cells are sources of IL-22, while the IL-22 receptor complex is reported to be restricted to cells of nonhematopoietic origin. The ligand-receptor distribution of IL-22-IL 22R permits immune cells to regulate responses of epithelial cells, endothelial cells, fibroblasts, and other tissue-resident stromal cells. This pathway appears to be critically important at barrier surfaces where epithelial cells play an active role in the initiation, regulation, and resolution of immune responses. Functional studies in murine model systems indicate that IL-22 has immunoregulatory properties in infection, inflammation, autoimmunity, and cancer. In these models, the functional consequences of IL-22 expression can be either pathologic or protective, depending on the context in which it is expressed. Therefore, advancing our understanding of the biology of IL-22-IL-22R may yield novel therapeutic targets in multiple human diseases. In this review, we discuss recent findings on the expression, regulation, and function of IL-22 at barrier surfaces, and offer insights into the next frontiers to be studied in this complex cytokine pathway. PMID- 21034971 TI - Specificity of the adaptive immune response to the gut microbiota. AB - The adaptive immune response to normal gut bacteria is part of a homeostatic process that is neither ignorance nor tolerance. Through both targeted and meta genome sequencing of the gut microbiota, we now know more about the microbial population that inhabits the gut environment than any previous generation. Defining the specificity of the adaptive immune response to gut symbionts and the impact of this specificity on the gut barrier function is still limited by lack of comprehensive data. The evolution of the gut microbiota over millenia with its host provides stability to the present-day microbiota in the presence and absence of the adaptive and innate immune system. Intrinsic factors within each member of the microbiota modulate the immunostimulatory capacity of gut bacteria. Three of these factors, ecological fitness, antigenic degeneracy, and pathogenicity, will control the level of immune response to a given organism in the community. Future research that defines the specificity of microbiota-reactive T and B cells will provide insight into both normal homeostasis as well as the pathology of inflammatory and metabolic diseases associated with the gut microbiome. PMID- 21034972 TI - Intestinal dendritic cells. AB - Dendritic cells (DCs) are specialized antigen-presenting cells that orchestrate innate and adaptive immune responses. The intestinal mucosa contains numerous DCs that are highly specialized in function. Mucosal DCs display a unique response to toll-like receptor ligands, are capable of driving immunoglobulin isotype switching to IgA, can imprint gut-homing receptors on T and B cells, and drive either T regulatory or Th17 cells depending on the analyzed subtype. These functions are partly cell autonomous and partly conferred by the local microenvironment. In this review, we will summarize the different DC subtypes present in the intestine and in the gut-associated lymphoid tissue (GALT), the unique characteristics of these subtypes, and how the local microenvironment can shape DC function. PMID- 21034973 TI - The many face-lifts of CD4 T helper cells. AB - Recent advances in stem cell research have redefined previous concepts of hematopoietic hierarchy, lineage commitment, and cell fate. The immune system is comprised of several well-defined cell lineages of which many exhibit high levels of plasticity or capacity in changing their phenotype. The CD4 T helper cells provide a peculiar example of apparently defined cell subsets, at times described as lineages, but also highly sensitive to tissue environmental cues that may change their fate. The classical Th1/Th2 CD4 T cell differentiation referred to for many years as the main CD4 T cell fate dichotomy and the later additions of CD4 helper T cell variants, such as T helper 17 (Th17) and induced regulatory T cells (iTreg), have added complexity but also doubts on the accuracy of defining CD4 T cell subsets as fixed T cell lineages. PMID- 21034974 TI - GALT: organization and dynamics leading to IgA synthesis. AB - Since its discovery more than four decades ago, immunoglobulin (Ig) A has been the subject of continuous and intensive studies. The major concepts derived were that the precursors of IgA plasma cells are generated in follicular organized structures with the help of T cells and the secreted IgAs provide protection against mucosal pathogens. However, only recently we began to appreciate that IgAs play key roles in regulation of bacterial communities in the intestine and that the repertoire of gut microbiota is closely linked to the proper functioning of the immune system. In this review, we highlight the complex and dynamic mutualistic relationships between bacteria and immune cells and discuss the sites and pathways leading to IgA synthesis in gut-associated lymphoid tissues (GALT). PMID- 21034970 TI - Innate signaling networks in mucosal IgA class switching. AB - The past 20 years have seen a growing interest over the control of adaptive immune responses by the innate immune system. In particular, considerable attention has been paid to the mechanisms by which antigen-primed dendritic cells orchestrate the differentiation of T cells. Additional studies have elucidated the pathways followed by T cells to initiate immunoglobulin responses in B cells. In this review, we discuss recent advances on the mechanisms by which intestinal bacteria, epithelial cells, dendritic cells, and macrophages cross talk with intestinal T cells and B cells to induce frontline immunoglobulin A class switching and production. PMID- 21034975 TI - Bronchus-associated lymphoid tissue (BALT) structure and function. AB - Bronchus-associated lymphoid tissue (BALT) is a constitutive mucosal lymphoid tissue adjacent to major airways in some mammalian species, including rats and rabbits, but not humans or mice. A related tissue, inducible BALT (iBALT), is an ectopic lymphoid tissue that is formed upon inflammation or infection in both mice and humans and can be found throughout the lung. Both BALT and iBALT acquire antigens from the airways and initiate local immune responses and maintain memory cells in the lungs. Here, we discuss the development and function of BALT and iBALT in the context of pulmonary immunity to infectious agents, tumors, and allergens as well as autoimmunity and inflammatory diseases of the lung. PMID- 21034977 TI - Revisiting the hand wipe versus gel rub debate: is a higher-ethanol content hand wipe more effective than an ethanol gel rub? AB - BACKGROUND: The Centers for Disease Control and Prevention's guidelines for hand hygiene state that the use of alcohol-based hand wipes is not an effective substitute for the use of an alcohol-based hand rub or handwashing with an antimicrobial soap and water. The objective of this study was to determine whether a hand wipe with higher ethanol content (65.9%) is as effective as an ethanol hand rub or antimicrobial soap in removing bacteria and spores from hands. METHODS: In two separate experiments, the hands of 7 subjects were inoculated with a suspension of Serratia marcescens or Geobacillus stearothermophilus. Subjects washed with each of 3 different products: 65.9% ethanol hand wipes (Sani-Hands ALC), 62% ethanol gel rub (Purell), and antimicrobial soap containing 0.75% triclosan (Kindest Kare). RESULTS: A total of 56 observations were analyzed for S marcescens removal and 70 observations were analyzed for G stearothermophilus removal. The rank order of product efficacy for both bacteria and spore removal was antibacterial soap > 65.9% ethanol hand wipes >62% ethanol hand rub. Mean S marcescens log reductions (+/-SD) for the 65.9% ethanol alcohol wipe, 62% ethanol alcohol rub, and antimicrobial foam soap were 3.44 +/- 0.847, 2.32 +/- 1.065, and 4.44 +/- 1.018, respectively (P < .001). Mean G stearothermophilus log reductions for the 65.9% ethanol wipe, 62% ethanol rub, and antimicrobial foam soap were 0.51 +/- 0.26, -0.8 +/- 0.32 increase over baseline, and 1.72 +/- 0.62, respectively (P < .001). CONCLUSION: The alcohol based hand wipe containing 65.9% ethanol was significantly more effective than the 62% ethanol rub in reducing the number of viable bacteria and spores on the hands. PMID- 21034978 TI - Urinary catheters in the emergency department: very elderly women are at high risk for unnecessary utilization. AB - BACKGROUND: Many of the urinary catheters (UCs) placed in the emergency department (ED) might not be necessary. We evaluated compliance with our institutional UC utilization guidelines and assessed factors influencing utilization. METHODS: We conducted a 12-week retrospective observational study evaluating UC utilization in all admissions from the ED. Data included reason for placement, presence of a physician's order for placement, resident physician involvement, and patient age and sex. RESULTS: Out of 4521 patients evaluated, 532 (11.8%) had a UC placed. Of these UCs, 371 (69.7%) were indicated, and 312 (58.6%) had a physician's order documented. The mean age of the patients who had a UC placed without an indication was 71.3 +/- 18.8 years, that of patients with an indication was 60.0 +/- 22.4 years (P < .0001), and that of patients who did not have a UC placed was 56.2 +/- 22.6 years (P < .0001). Half of the women aged >=80 years who had a UC placed did not have an indication according to our institutional guidelines. Multivariate logistic regression showed that women were 1.9 times more likely than men, and those age >=80 years were 2.9 times more likely than those age <=50 years, to have a UC placed without an indication. CONCLUSION: Very elderly women are at high risk for inappropriate UC utilization in the ED. Interventions are needed to address this vulnerable population. PMID- 21034979 TI - Effectiveness of a simple intervention for prevention of catheter-associated urinary tract infections in a community teaching hospital. AB - BACKGROUND: Catheter-associated urinary tract infection (CA-UTI) is the most common health care-associated infection. Instrumentation of the urinary tract, mainly urinary catheterization, is the most important risk factor for CA-UTI. It is believed that proper catheter management can reduce the incidence of CA-UTI. METHODS: This was a prospective preintervention and postintervention study conducted to assess the effect of an intervention aimed at preventing CA-UTI. A reminder sticker was placed on each patient's medical record binder to remind the physicians to consider discontinuing any unnecessary urinary catheters. RESULTS: There was a statistically significant increase in the number of appropriately retained urinary catheters at 3 months (57% vs 73%; P = .007) and 6 months postintervention (57% vs 86%; P < .001). There was also a statistically significant reduction in the rate of CA-UTI after 3 months (7.02 vs 2.08; P < .001) and 6 months postintervention (7.02 vs 2.72; P < .001). CONCLUSION: A simple intervention using a sticker placed on patients' medical record binder to remind physicians to remove unnecessary urinary catheters can significantly increase the appropriate utilization of urinary catheters and decrease the rate of CA-UTI in community teaching hospitals. PMID- 21034976 TI - Host-bacterial symbiosis in health and disease. AB - All animals live in symbiosis. Shaped by eons of co-evolution, host-bacterial associations have developed into prosperous relationships creating mechanisms for mutual benefits to both microbe and host. No better example exists in biology than the astounding numbers of bacteria harbored by the lower gastrointestinal tract of mammals. The mammalian gut represents a complex ecosystem consisting of an extraordinary number of resident commensal bacteria existing in homeostasis with the host's immune system. Most impressive about this relationship may be the concept that the host not only tolerates, but has evolved to require colonization by beneficial microorganisms, known as commensals, for various aspects of immune development and function. The microbiota provides critical signals that promote maturation of immune cells and tissues, leading to protection from infections by pathogens. Gut bacteria also appear to contribute to non-infectious immune disorders such as inflammatory bowel disease and autoimmunity. How the microbiota influences host immune responses is an active area of research with important implications for human health. This review synthesizes emerging findings and concepts that describe the mutualism between the microbiota and mammals, specifically emphasizing the role of gut bacteria in shaping an immune response that mediates the balance between health and disease. Unlocking how beneficial bacteria affect the development of the immune system may lead to novel and natural therapies based on harnessing the immunomodulatory properties of the microbiota. PMID- 21034980 TI - Patients' experiences of acquiring a deep surgical site infection: an interview study. AB - BACKGROUND: The negative impact of surgical site infection (SSI) in terms of morbidity, mortality, additional costs, and length of stay (LOS) in the hospital is well described in the literature, as are risk factors and preventive measures. Given the lack of knowledge regarding patients' experiences of SSI, the aim of the present study was to describe patients' experiences of acquiring a deep SSI. METHODS: Content analysis was used to analyze data obtained from 14 open interviews with participants diagnosed with a deep SSI. RESULTS: Patients acquiring a deep SSI suffer significantly from pain, isolation, and insecurity. The SSI changes physical, emotional, social, and economic aspects of life in extremely negative ways, and these changes are often persistent. CONCLUSION: Health care professionals should focus on strategies to enable early diagnosis and treatment of SSIs. The unacceptable suffering related to the infection, medical treatment, and an insufficient patient-professional relationship should be addressed when planning individual care, because every effort is needed to support this group of patients and minimize their distress. All possible measures should be taken to avoid bacterial contamination of the surgical wound during and after surgery to prevent the development of SSI. PMID- 21034981 TI - Evaluation of sporicidal activities of selected environmental surface disinfectants: carrier tests with the spores of Clostridium difficile and its surrogates. AB - BACKGROUND: The emergence of Clostridium difficile as a major nosocomial pathogen points to the need for safe, effective, and fast-acting environmental sporicides for infection prevention and control. Available and fast-acting sporicides are generally corrosive and unsafe for both humans and the environment. METHODS: We evaluated chlorine bleach (500 and 5000 ppm) and a gel containing 4.5% of accelerated hydrogen peroxide against the spores of C difficile and its surrogates Bacillus subtilis and Clostridium sporogenes with contact times of 1, 5, and 10 minutes at 20 degrees C +/- 2 degrees C using a quantitative carrier test (QCT-2), which is a standard (ASTME2197) of American Society for Testing and Materials International. RESULTS: The gel and the higher level of bleach inactivated >=6-log(10) of viable spores of all 3 types in 10 minutes but were unable to do so after 1 and 5 minutes. The lower level of bleach showed virtually no activity even after 10 minutes. The gel could keep the treated surface wet for the entire 10 minutes, whereas the bleach became visibly dry in approximately 4 minutes and needed reapplication. CONCLUSION: The gel, with no off-gassing and designed especially for use on toilet bowls to allow for the required dwell time on vertical surfaces with one application, is a potential alternative to high levels of bleach. PMID- 21034982 TI - Occupational risk for human immunodeficiency virus, hepatitis B, and hepatitis C infection in health care workers in a teaching hospital in Indonesia. PMID- 21034983 TI - Nutrition and the skin: "You are what you eat" Part II. PMID- 21034984 TI - Nutrition and acne. AB - There are significant data supporting the role of diet in acne. Our Western diet includes many dairy sources containing hormones.. The natural function of milk being to stimulate growth, it contains anabolic steroids as well as true growth hormones and other growth factors. The presence of 5alpha-pregnanedione, 5alpha androstanedione, and other precursors of 5alpha-dihydrotestosterone add to the potency of milk as a stimulant of acne. In addition, foods with significant sugar content and other carbohydrates yielding high glycemic loads affect serum insulin and insulin-like growth factor-1 levels, both of which promote increased production of available androgens and the subsequent development of acne. PMID- 21034985 TI - Atopic dermatitis and nutrition. AB - Atopic dermatitis, a chronic disease with no cure, currently affects almost one fifth of the population of industrialized nations. Treatment can be challenging for physicians and patients alike. Children are commonly affected, making it even more difficult to find safe therapeutic options, especially in severe disease. Interest in diet and nutrition has increased during the last few years. Nutritional interventions are both intriguing and accessible for many patients. Given the recent expansion of the field of nutrition in the realm of medicine and in popular culture, it is important for the dermatologist to be knowledgeable about the risks and benefits of nutritional interventions. This contribution reviews the current literature on the role of nutrition in atopic dermatitis, from dietary restriction to dietary supplementation, from traditional interventions such as vitamins and minerals to the emerging fields of probiotics and essential fatty acids, and from the prenatal period through infancy and adulthood. PMID- 21034986 TI - Nutrition and psoriasis. AB - Nutritional supplementation may provide a viable treatment alternative in patients with psoriasis. Randomized, controlled trials have shown the effectiveness of topical vitamin A and D derivatives, intravenous omega-3 fatty acids, oral inositol, and various combined therapies. Dual therapies of ultraviolet B phototherapy and fish oil, retinoids and thiazolidinediones, and cyclosporine and a low-calorie diet were effective in the treatment of psoriasis in randomized, controlled trials. This contribution also reviews the potential negative effect of alcohol and the potential positive effects of vitamin B(12), selenium, retinoic acid metabolism-blocking agents, and a gluten-free diet in the treatment of psoriasis. PMID- 21034987 TI - Nutrition and bullous skin diseases. AB - Autoimmune and nonautoimmune bullous diseases can both be associated with significant morbidity and mortality. Although our understanding of the pathogenic mechanisms of these diseases has increased tremendously, there is still much to learn about the various factors affecting their onset, course, and therapy. In recent years, increasing information has been published about the effect of vitamins, minerals, and other nutrients on bullous skin diseases. Some factors are believed to be inducers (thiol and phenol-containing foods in pemphigus), whereas others are believed to be protective (antioxidants in cutaneous porphyrias). This contribution reviews the evidence in the literature of the role of various dietary factors in bullous diseases, including the nonautoimmune and the deficiency dermatoses. Additional studies and new investigations are needed to provide a better understanding of the specific associations of dietary factors with bullous diseases and better management for patients affected by these conditions. PMID- 21034988 TI - Nutrition and melanoma prevention. AB - Melanoma has continued to rise in incidence despite public efforts to promote sun protection behaviors. Because sunscreen use does not completely prevent skin cancer induced by ultraviolet radiation, additional chemopreventive methods for protecting against and reversing the effects of ultraviolet photodamage need evaluation. Recent years have brought increased interest in dietary factors, such as natural botanicals and vitamins, for the prevention of melanoma. This contribution provides a narrative review of the relevant, nutrition-related literature found by searching the keywords "melanoma chemoprevention," "nutrition and melanoma," "dietary botanicals and melanoma prevention," "green tea and melanoma," "vitamin D and melanoma," and "vitamin E and melanoma" in the PubMed database. Although randomized controlled trials of humans are lacking, basic science and epidemiologic studies show promising benefits of many natural products in chemoprevention for melanoma. Future studies, hopefully, will yield concrete answers and clarify the role of commonly available dietary nutrients in melanoma chemoprevention. PMID- 21034989 TI - Nutrition and nonmelanoma skin cancers. AB - The incidence of nonmelanoma skin cancer is increasing every year. Basal cell carcinoma and squamous cell carcinoma are the two major types of nonmelanoma skin cancer. Among other factors, understanding the potential role of nutrients in the development, progression, and treatment of nonmelanoma skin cancer is critical. This contribution provides a review of the nutrients that have been more extensively investigated in the literature with regard to nonmelanoma skin cancer, including dietary fats, retinol, carotenoids, vitamin C, vitamin D, vitamin E, selenium, copper, iron, zinc, green tea, and black tea. PMID- 21034990 TI - Vitamin D and the skin. AB - Vitamin D is a fat-soluble nutrient that humans obtain through the diet and by synthesis in the skin upon exposure to ultraviolet B. Vitamin D is then converted by the liver to 25-hydroxyvitamin D, its major circulating form. This form is the best indicator of vitamin D nutritional status and is easily measured. Under the influence of parathyroid hormone, the kidney then converts 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D, the biologically active, hormonal form of the nutrient that is important in the metabolism of calcium and phosphorus and is critical in building and maintaining healthy bones. Many cell types outside of the skeletal system, including various cells in the skin, also express the vitamin D receptor. In addition, many cell types convert circulating 25-hydroxyvitamin D to 1,25 dihydroxyvitamin D for local use. This metabolite has been shown to exert potent effects on cellular differentiation, cellular proliferation, and immune regulation. It is theorized that by these mechanisms vitamin D and its analogues are effective treatment options for psoriasis and other skin diseases. Insufficient vitamin D nutritional status has been associated with a host of other diseases, most notably cancer. There is evidence that supplementation with vitamin D reduces the overall incidence of cancer, although current evidence is insufficient to prove a causative effect. Sunscreen use blocks the ability of the skin to photosynthesize vitamin D, although the effect this has on the vitamin D status of the general population is unclear. PMID- 21034991 TI - Syndromes associated with nutritional deficiency and excess. AB - Normal functioning of the human body requires a balance between nutritional intake and metabolism, and imbalances manifest as nutritional deficiencies or excess. Nutritional deficiency states are associated with social factors (war, poverty, famine, and food fads), medical illnesses with malabsorption (such as Crohn disease, cystic fibrosis, and after bariatric surgery), psychiatric illnesses (eating disorders, autism, alcoholism), and medications. Nutritional excess states result from inadvertent or intentional excessive intake. Cutaneous manifestations of nutritional imbalance can herald other systemic manifestations. This contribution discusses nutritional deficiency and excess syndromes with cutaneous manifestations of particular interest to clinical dermatologists. PMID- 21034992 TI - Nutrition and skin diseases in veterinary medicine. AB - Veterinarians are confronted with a variety of food and nutrition-related skin diseases, with cutaneous food adverse reaction the most common in small animal dermatology. In addition to canine atopic dermatitis, cutaneous food adverse reaction has been an area of interest for extensive research for the last decade. Nutritional deficiencies and toxicoses are rare these days due to commercially available high-quality diets; however, poorly stored diets, inadequate husbandry of exotic pets, or problems in a farm animal environment may result in zinc, vitamin A, vitamin C, and fatty acid, or copper deficiency. Inherited deficiencies due to abnormal zinc absorption through the gastrointestinal tract must be considered in Nordic breed dogs and goats. PMID- 21034993 TI - Antioxidant supplements and their risk of skin cancers. PMID- 21034994 TI - Medicine and the Holocaust. PMID- 21035001 TI - In defense of case series: hip SCFE, shoulder instability and arthritis, double bundle ACL cyclops lesions, and elbow OCD. PMID- 21035002 TI - Principle considerations in anatomic ACL reconstruction. PMID- 21035004 TI - Femoral nerve block does provide significant analgesia after anterior cruciate ligament reconstruction. PMID- 21035006 TI - The clinical relevance of cartilage regeneration and related basic science research: regenerating the orthopaedic clinician-scientist. PMID- 21035008 TI - Arthroscopy classics. Arthroscopic partial medial meniscectomy: an analysis of unsatisfactory results. PMID- 21035007 TI - Arthroscopic Bankart-Bristow-Latarjet procedure: the development and early results of a safe and reproducible technique. AB - PURPOSE: To evaluate the reproducibility and safety of a novel arthroscopic technique combining a Bristow-Latarjet procedure with a Bankart repair and to report the early clinical and radiologic results. METHODS: Forty-seven consecutive patients with glenoid bone loss and capsular deficiency were treated with this all-arthroscopic technique; six patients had a failed arthroscopic capsulolabral repair. The coracoid fragment was osteotomized, passed with the conjoined tendon through the subscapularis muscle, and fixed in the standing position with a cannulated screw on the abraded glenoid neck. The capsule and labrum were then reattached on the glenoid rim, leaving the coracoid bone block in an extra-articular position. Potential intraoperative and postoperative complications were recorded. All patients were reviewed and had postoperative radiographs; 35 had computed tomography scans. RESULTS: The procedure was performed entirely arthroscopically in 41 of 47 patients (88%); a conversion to open surgery was needed in 6 patients (12%). The axillary nerve was identified in all cases, and no neurologic injuries were observed. No patient had any recurrence of instability at the most recent follow-up (mean, 16 months). The mean Rowe score was 88 +/- 16.7, and the mean Walch-Duplay score was 87.6 +/- 12.9. The Subjective Shoulder Value was 87.5% +/- 12.7%. The bone block was subequatorial in 98% of the cases (46 of 47) and flush to the glenoid surface in 92% (43 of 47); it was too lateral in 1 (2%) and too medial (>5 mm) in 3 (6%). There was 1 bone block fracture and 7 migrations. CONCLUSIONS: The arthroscopic Bristow-Latarjet-Bankart procedure is reproducible and safe. This procedure allows restoration of shoulder stability in patients with glenoid bone loss and capsular deficiency, as well as in the case of failed capsulolabral repair. Arthroscopy offers the advantage of providing adequate visualization of both the glenohumeral joint and the anterior neck of the scapula, allowing accurate placement of the bone block and screw. Surgeons should be aware that the procedure is technically difficult and potentially dangerous because of the proximity of the brachial plexus and axillary vessels. Training on cadaveric specimens and transition from open to mini-open and, finally, to all arthroscopic is recommended. LEVEL OF EVIDENCE: Level IV, therapeutic case series. PMID- 21035009 TI - Outcomes and risks of operative treatment of rupture of the anterior cruciate ligament in children and adolescents. AB - PURPOSE: The aim of this meta-analysis was to evaluate the clinical outcomes and risks of anterior cruciate ligament (ACL) surgery in children and adolescents. METHODS: We electronically searched Medline, the Cochrane Controlled Trial Database, Embase, and Medpilot for studies on surgical treatment for ACL ruptures in skeletally immature patients. We extracted baseline demographics, follow-up intervals, surgical details (i.e., ligament suture or reconstruction, physeal sparing or transphyseal techniques, type of transplant, and methods of fixation). Endpoints comprised rates of growth disturbances and reruptures, as well as knee function (measured by the International Knee Documentation Committee's documentation system and the Lysholm score). Unweighted overall effect sizes (risks, risk ratios [RRs], and means of functional scores) were estimated by use of crude nominators and denominators, and random-effects meta-regression analysis was used for weighted data synthesis. RESULTS: A total of 55 articles reporting on 935 patients (median age, 13 years; range, 1.5 to 16 years) were suitable for the study. After a median follow-up of 40 months (range, 14 to 89 months), the weighted rate of leg-length differences or axis deviations was 1.8% (95% confidence interval [CI], 0% to 3.9%] and that of reruptures was 4.8% (95% CI, 2.9% to 6.7%). Excellent or good function (International Knee Documentation Committee grade A or B) was achieved in 84.2% (95% CI, 75.8% to 92.6%) of all knees, and Lysholm scores averaged 96.3 (95% CI, 95.5 to 97.2). Transphyseal reconstruction was associated with a significantly lower risk of leg-length differences or axis deviations compared with physeal-sparing techniques (1.9% v 5.8%; RR, 0.34; 95% CI, 0.14 to 0.81) but had a higher risk of rerupture (4.2% v 1.4%; RR, 2.91; 95% CI, 0.70 to 12.12). Sutures did not result in any growth disturbances, with a weighted rerupture rate of 4.6% (95% CI, 2.6 to 6.7). Fixation far from the joint line fared better than close fixation with regard to this endpoint (1.4% v 3.2%; RR, 0.42; 95% CI, 0.09 to 1.93). Bone-patellar tendon bone grafts, which are also less likely to fail, were associated with higher risks of leg-length differences or axis deviations than were hamstrings (3.6% v 2.0%; RR, 1.82; 95% CI, 0.66 to 5.03). Meta-regression did not show a significant impact of the publication year on event rates. CONCLUSIONS: This meta-analysis showed low rates of leg-length differences or axis deviations and graft failures after ACL reconstruction in skeletally immature patients. Hamstring transplants may lower the risk of leg-length differences or axis deviations, and physeal sparing techniques may increase the risk. Randomized controlled trials are needed to clarify important issues in managing ACL ruptures in children and adolescents. LEVEL OF EVIDENCE: Level IV, meta-analysis of case series. PMID- 21035010 TI - The "coiling-up procedure": a novel technique for extra-articular arthroscopy. AB - The "coiling-up procedure" is a novel technique for extra-articular arthroscopy. A coil-shaped lifter is used to create the extra-articular working space, and a dry arthroscopy is performed. It can be combined with conventional intra articular arthroscopy to enable direct vision from both inside and outside the joint. We have successfully used this technique to perform a vastus lateralis release in cases of painful bipartite patella. This is an innovative technique that offers the possibility of expanding the indications for extra-articular arthroscopy to other areas of the body. We describe in detail the technique for this new procedure in the knee. PMID- 21035011 TI - Quality improvement articles: maximizing the impact through adoption of the standards for quality improvement reporting excellence guidelines. PMID- 21035012 TI - Predictors of exclusive breast-feeding in early infancy: a survey report from Phnom Penh, Cambodia. AB - BACKGROUND: Exclusive breast-feeding (EBF) is recommended in the first 6 months of an infant's life. This study aims to investigate the present status of infant feeding practices and identify factors that affect EBF practices during the first 6 months following infant birth in Phnom Penh, Cambodia. METHODS: A cross sectional survey with a semistructured questionnaire was given to 312 mothers with children aged 6 to 24 months who visited the immunization clinic in the National Maternal and Child Health Centre in Phnom Penh, Cambodia, from December 2005 to February 2006. RESULTS: Eighty-three percent of mothers fed breast milk exclusively in the first month, whereas only 51.3% continued EBF in the first 6 months. Within 30 minutes after delivery, 39% of mothers began breast-feeding. Results from logistic regression analysis indicate that the lack of a maternal antenatal EBF plan (odds ratio [OR] = 10.01, 95% confidence interval [CI] = 3.68 27.24, p < .001), working mothers (OR = 4.71, 95% CI = 2.77-8.01, p < .001), and lack of paternal attendance at breast-feeding classes (OR = 1.93, 95% CI = 1.13 3.28, p < .05) have independently positive associations with cessation of EBF during the first 6 months of infant life. CONCLUSION: The findings have helped to identify some important factors affecting EBF practices in the study area in Cambodia. The findings revealed that it is important to educate pregnant mothers, probably through exposure to trained midwives and media, so they may recognize the significance of EBF and will develop intention and plan to feed their babies, keeping in mind the benefits it may yield. Paternal involvement in breast-feeding classes may increase their awareness and consequently complement EBF practices. Finally, development of conducive working environments and policies for working mothers should be carefully explored because it could have positive influence in better care and promotion of EBF. PMID- 21035013 TI - Unaccompanied hospitalized children: a review of the literature and incidence study. AB - The aim of this study was to review literature on unaccompanied hospitalized children and report the incidence at a pediatric hospital over 2 weeks. The philosophical model of most pediatric hospitals is family-centered care (FCC) and reducing separation effects. Although the FCC model includes parents/guardians as collaborators and participants in the care of the child, parents cannot always be present. Nurses try to meet the needs of unaccompanied children. Children and parents express that they want to be together, but many parents have obstacles to participation including increased expectations. The incidence study found that about one third of children were sometimes unaccompanied. PMID- 21035014 TI - Nursing students apply evidence-based research principles in primary burn prevention projects. AB - The purpose of this project was for registered nursing students in a baccalaureate nursing program to look at different prevention strategies that could be utilized in the community to impact change in a family's burn prevention knowledge. The prevention strategies and their corresponding interventions were written in a narrative form, and then a poster was created to serve as a supplemental visual aid for the information. Firefighters from a local fire department evaluated posters and their abstracts based on criteria developed by the students. Five posters were revised and submitted to a national burn prevention contest. Students gained valuable experience in developing and revising evidence-based research (EBR) projects to promote community education in primary burn prevention with firefighter collaboration. PMID- 21035015 TI - Expressive arts in pediatric orientation groups. AB - Children admitted to a pediatric unit experience separation or loss from everyday supports while undergoing medical tests or procedures in an environment that children characterize as distressing. A Canadian multidisciplinary hospital team conducted a pilot project that provided children experiencing unplanned admissions to come together to explore, discuss, enact, and make sense of the stress in the hospital environment. The children participated in postadmission orientation groups engaging in improvised skits in which they shared experiences, listened to each other's feelings, and began to problem solve. Primary care staff provided scaled responses and clinical judgements before and after the groups. Staff report that children's fears, anger, and withdrawal improved after the shared group activities. PMID- 21035016 TI - Korean immigrant discipline and children's social competence and behavior problems. AB - The goal of this correlational study was to explore the relationship between Korean immigrant discipline (e.g., positive, appropriate, and harsh discipline) and children's social competence and behavior problems. Self-report data were collected from 58 mothers and 20 fathers of children aged from 3 to 8 years. Only paternal harsh discipline was positively correlated with children's behavior problems. Among specific discipline strategies, maternal physical affection, correcting misbehaviors, and reasoning were positively correlated with children's social competence. Paternal physical punishment (e.g., spanking, hitting, and raising arms) was positively correlated with children's behavior problems. Immigrant fathers need to learn alternative ways of managing children's misbehaviors. PMID- 21035017 TI - Adherence to antiretroviral therapy in pediatric patients with human immunodeficiency virus (HIV-1). AB - The evaluation of HIV treatment adherence is essential to manage the development of resistant mutations, treatment failure, and disease progression in patients with HIV-1 infection; however, none of the commonly used measures of treatment adherence have been found to be accurate. The objective of this study was to evaluate three treatment adherence measures (caregiver reports, pharmacy refill, and appointment maintenance data) in association with viral load suppression in pediatric patients with HIV-1 infection. Although viral suppression was not found to be significantly associated with adherence defined by any single measure, treatment adherence could be predicted if all three measures were in agreement. PMID- 21035018 TI - Health care transitions among youth with disabilities or special health care needs: an ecological approach. AB - This literature review of 46 articles uses the ecological model as a framework for organizing concepts and themes related to health care transition among youth with disabilities or special health care needs (SHCN). Transition involves interactions in immediate and distal environmental systems. Important interactions in immediate environments include those with family members, health care providers, and peers. Activities in distal systems include policies at the governmental and health system levels. The ecological model can help researchers and practitioners to design experimental interventions in multiple settings that ensure smooth transitions and support the well-being of youth with disabilities or SHCN. PMID- 21035019 TI - A community health concern: respiratory syncytial virus and children. AB - Respiratory syncytial virus (RSV) is a significant health issue. Nearly all children contract RSV by 3 years of age. This virus causes mild cold-like symptoms in older children and adults. However, in infants and toddlers, it causes serious lower respiratory tract infections. Recovery from RSV can be lengthy, and caring for an unwell child can become a burden for a family. Prevention plans for those children that are at highest risk have been helpful in reducing the incidence of RSV. The American Academy of Pediatrics outlines the use of Palivizumab as part of its RSV prevention guidelines. PMID- 21035020 TI - Medication administration errors and the pediatric population: a systematic search of the literature. AB - There are a variety of factors that make the pediatric population more susceptible to medication errors and potential complications resulting from medication administration including the availability of different dosage forms of the same medication, incorrect dosing, lack of standardized dosing regimen, and organ system maturity. A systematic literature search on medication administration errors in the pediatric population was conducted. Five themes obtained from the systematic literature search include incidence rate of medication administration errors; specific medications involved in medication administration errors and classification of the errors; why medication administration errors occur; medication error reporting; and interventions to reduce medication errors. PMID- 21035022 TI - Far from reliable: pH testing in the neonatal intensive care unit. PMID- 21035021 TI - Use of complementary and alternative medical interventions for the management of procedure-related pain, anxiety, and distress in pediatric oncology: an integrative review. AB - This integrative review aims to identify evidence in four electronic databases (MEDLINE, CINAHL, PsyINFO, and COCHRANE) regarding the effectiveness of complementary and alternative medical interventions, either alone or as an adjunct to pharmacological therapy, in alleviating procedure-related pain, anxiety, and distress in children and adolescents with cancer. A total of 32 articles met inclusion criteria. Results suggest that mind-body interventions, including hypnosis, distraction, and imagery, may be effective, alone or as adjuncts to pharmacological interventions, in managing procedure-related pain, anxiety, and distress in pediatric oncology. PMID- 21035023 TI - Providing confidential care to teenagers. PMID- 21035024 TI - It is time to give the new technologies a try. PMID- 21035025 TI - Research commentary--educational interventions: essential strategies for pediatric nursing practice and research. PMID- 21035026 TI - Klinefelter syndrome: awareness and index of suspicion. PMID- 21035027 TI - Factors influencing treatment delay for patients with acute myocardial infarction. AB - The purpose of this study was to identify cognitive, social, and emotional influences of individuals delaying treatment during an acute myocardial infarction (AMI). In a multiple regression analysis, the following were predictors of long treatment delay in arrival to the emergency department after cardiac symptom onset: being home, having more ability to control symptoms, and being in a public place. Predictors of short treatment delay were thinking that symptoms were heart related, calling 911, having a high pain scale, and telling someone else about the symptoms. Nurses can use this study to identify potential responses and situations that may affect patient decision delay in the future. PMID- 21035028 TI - Compassion fatigue in nurses. AB - Compassion fatigue, trigger situations, and coping strategies were investigated in hospital and home care nurses. The Professional Quality of Life Scale measured compassion fatigue, compassion satisfaction, and burnout. Narrative questions elicited trigger situations and coping strategies. Compassion fatigue scores were significantly different between nurses who worked 8- or 12-hour shifts. Fifteen percent of the participants had scores indicating risk of the compassion fatigue. There were significant differences in compassion satisfaction, depending on the unit worked and time as a nurse. The most common category of trigger situations was caring for the patient. Work-related and personal coping strategies were identified. PMID- 21035029 TI - Illuminating hospital discharge planning: staff nurse decision making. AB - This qualitative study proposed to examine staff RN's decision making related to discharge planning and perceptions of their role. Themes resulting from interviews were "following the script" and "RN as coordinator." The decision to consult a discharge planner occurred when the patient's situation did not follow the RN's expectations. Discharge planning for nonroutine situations was considered disruptive to the RN's workflow. The RN's role was limited to oversight when a discharge planner was involved. Understanding RNs' decision making in this key process provides valuable insights into differentiating routine from nonroutine patient situations and deploying appropriate resources in a timely fashion. PMID- 21035030 TI - Voices from the frontline: Perceptions and needs of nurses involved in a nosocomial cluster of tuberculosis infection. AB - Little is known about the psychological aspects of health care workers who contract tuberculosis (TB). This study explored the perceptions and the needs of nurses who were involved in a nosocomial cluster of TB infection in Taiwan. Using a phenomenological research design, we conducted semistructured interviews with nine participants. The data management was processed by Colaizzi's method. The result reveals that nursing staff members who occupationally contracted TB undergo two phases. From the detection of their infection to recovery, they experienced different perceptions and needs. The hospital should be mandated to accommodate nurses' varying needs accordingly. Clinical-implication-related infection control strategies, grouped into three levels of prevention, are discussed. PMID- 21035031 TI - An instrument to measure job satisfaction of certified nurse assistants. AB - We first presented the steps taken to develop the nursing home certified nurse assistant job satisfaction questionnaire (NH-CNA-JSQ) and, second, the psychometric properties of this instrument. Certified nurse assistants (CNAs) from 22 nursing homes in Pennsylvania were mailed the NH-CNA-JSQ. Of the 726 surveys mailed, 479 usable surveys were returned, giving a 66% response rate. The factor analyses show that the items were representative of the underlying factors, representing seven subscales. The percentage of CNAs not providing responses for each question was low (1.5%), and the floor and ceiling effects of the responses for each of the 19 questions were low (i.e., 9.4% and 5.2%, respectively). The item-scale internal consistency analyses determined that the correlation of items within indexes was higher than those of items with other indexes. Cronbach's alpha values for the domains ranged from .72 to .83 and were all higher than the usually recommended levels. Criterion validity was high (.77) as was the index of content validity (p > .05). We believe that we have produced a short psychometrically sound job satisfaction instrument for use in nursing homes. PMID- 21035032 TI - Decision-making capacity and informed consent to participate in research by cognitively impaired individuals. AB - Obtaining informed consent is a fundamental part of conducting research that balances the need for participant autonomy and calls on the principal investigator to exercise beneficence. This is especially true in research involving persons with dementia and mild cognitive impairment where the ability to understand and reason may be compromised. Performing an assessment of decision making capacity to consent to research should be the first step in helping the researcher decide who signs the consent. This article reviews the current literature available on instrumentation and procedures for capacity assessment, and in the absence of universal guidelines offers implications and suggestions for practice. PMID- 21035033 TI - A multistep recruitment strategy to a participant-intensive clinical trial. AB - Adequate access to well-informed study participants is key to rapid recruitment and retention to randomized controlled clinical trials (RCTs). We describe a novel seven-step recruitment process for enrolling participants in a recently completed drug and exercise RCT in fibromyalgia. The majority decided not to participate during the screening process. Approximately 7% dropped out after beginning the intervention. All participants were enrolled within 14 months, which was 21 months ahead of the projected timeline. We suggest that this strategy ultimately decreased costs, made efficient use of research staff, and provided a consistent message to participants about the RCT. PMID- 21035034 TI - Clinical trial recruitment challenges with older adults with cancer. AB - Older adults continue to be disproportionately represented in research studies and cancer-related clinical trials. As survival rates for patients with cancer continue to increase, it is critical that we begin to gather data on how to provide the best care to the patient population where cancer is most prevalent. The purpose of this article was to provide an overview of barriers encountered during recruitment to clinical trials of older patients with cancer. Two clinical trials involving older patients with cancer are presented to describe strategies used by the principal investigators to enhance recruitment and enrollment to their clinical research trials. These two exemplars suggest that planning and regular meetings by the research team and transparent communication are essential for successful clinical trial recruitment of older patients with cancer. PMID- 21035035 TI - Patients' perspectives of falling while in an acute care hospital and suggestions for prevention. AB - Patient falls and falls with injury are the largest category of reportable incidents and a significant problem in hospitals. Patients are an important part of fall prevention; therefore, we asked patients who have fallen about reason for fall and how falls could be prevented. There were two categories for falls: the need to toilet coupled with loss of balance and unexpected weakness. Patients asked to be included in fall risk communication and asked to be part of the team to prevent them from falling. Nurses need to share a consistent and clear message that they are there for patient safety. PMID- 21035036 TI - Nurses' experiences in spirituality and spiritual care in Hong Kong. AB - Nurses emphasize spiritual care in maintaining patients' holistic health; however, the provision for spiritual care is found to be inadequate. The limited study in exploring the nurses' perception on applying spiritual care in Hong Kong has been noted. This descriptive phenomenological study investigated the experiences of spirituality and spiritual care in Hong Kong from the nurses' perspective. Ten nurses were purposively invited for an unstructured interview. Thematic analysis was used for data analysis, and three themes emerged: the meaning of spirituality, benefits of applying spiritual care, and difficulties in applying spiritual care. This study provided preliminary insights into the development of spiritual care in Hong Kong. PMID- 21035037 TI - Molecular basis of disease: arterial hypertension. PMID- 21035038 TI - Who is packing your parachute? PMID- 21035039 TI - Abnormal proximal musculotendinous junction of the peroneus brevis muscle as a cause of peroneus brevis tendon tears: a cadaveric study. AB - Abnormal musculotendinous distal extension of the peroneus brevis has been implicated as a possible cause of peroneus brevis tendon tears. We investigated this relationship in 58 (46 male) fresh human cadavers. Torn lesions were classified according to Sobel et al. Musculotendinous distal extension of the peroneus brevis was measured in each ankle as the vertical distance from the musculotendinous junction of the peroneus brevis to the tip of the fibula. Tendons with and without tears were compared by sex, age at death, height, musculotendinous distal extension of the peroneus brevis, the common sheath bifurcation-fibular tip distance, the peroneus brevis and longus width at the musculotendinous junction, fibular groove depth, peroneal tubercle height, superior-inferior peroneal retinaculum wideness, and the presence of the peroneus quartus or an accessory peroneal muscle. Of 115 evaluable tendons, 15 (13%) had tears. All came from men. The average distance from the musculotendinous junction to the tip of the fibula was 27.0 mm in tendons with tears and 16.4 mm in tendons without (P = .04) Male sex (P = .03), age at death (P = .03), height (P = .04), and fibular groove depth (P = .003) were also related to the presence of tears. Our results do not support a relationship between abnormal musculotendinous distal extension of the peroneus brevis and peroneus brevis tendon tears; rather, proximal extension of the peroneus brevis musculotendinous junction may be related to peroneus brevis tendon tears. PMID- 21035040 TI - Chopart joint injury: a study of outcome and morbidity. AB - Injuries involving the Chopart joint complex are relatively rare and frequently missed or misdiagnosed, often leading to a poor functional outcome. This study was performed to determine the outcome and morbidity in patients with Chopart joint injuries, and to increase awareness of this severe injury. Patients with a Chopart dislocation or fracture-dislocation, treated between January 2004 and January 2010, were identified using the appropriate diagnosis code and reviewing all radiographs of patients diagnosed with hindfoot or midfoot injuries treated at our institution. Data on patient characteristics, trauma mechanism, delay, and treatment were collected using patient files, operation reports, and by reviewing radiographs. Outcome was determined using the American Orthopaedic Foot & Ankle Society midfoot score and a visual analog scale satisfaction score, in patients with a minimum follow-up of 6 months. Nine patients (1.5 per year) were identified, including 6 women. The mean patient age was 41.6 +/- 25.1 years. The trauma mechanism was sprain or sports injury in 5 (55.6%), motor vehicle accident in 3 (33.33%), and a fall from height in 1 (11.11%) case. Seven patients with an average follow-up of 31.3 +/- 19.2 months reported a mean American Orthopaedic Foot & Ankle Society midfoot score of 72 (range, 32-100) points and a mean visual analog scale score of 7.1 (range, 5-10). Four (57.14%) patients still experienced pain or had limitations in daily activities at the time of the final follow-up. This study supports the conclusion of previous studies, which stated that a higher level of awareness is needed to prevent permanent disability. PMID- 21035041 TI - Clinical outcomes after isolated periarticular osteotomies of the first metatarsal for hallux rigidus: a systematic review. AB - Isolated periarticular osteotomy of the first metatarsal has been proposed for treatment of hallux rigidus due to the perceived ability to "decompress" the first metatarsophalangeal joint through axial shortening, as well as plantar displacement of the first metatarsal head to correct purported elevation. Additionally, isolated periarticular osteotomy of the first metatarsal has been proposed for treatment of hallux rigidus because of the perceived safety and efficacy. Furthermore, it has been proposed that undergoing isolated periarticular osteotomy of the first metatarsal does not prevent the ability to perform revision surgery. The author undertook a systematic review of electronic databases and other relevant sources to identify material relating to the clinical outcomes and need for surgical revision after isolated periarticular osteotomy of the first metatarsal for hallux rigidus. Information from peer reviewed journals, as well as from non-peer-reviewed publications, abstracts and posters, and unpublished works, was also considered. In an effort to procure the highest quality studies available, studies were eligible for inclusion only if they involved consecutively enrolled patients undergoing isolated periarticular osteotomy of the first metatarsal for hallux rigidus, involved a prospective study design, included some form of objective and subjective data analysis, evaluated patients at a mean follow-up >=12 months' duration, and included details of complications requiring surgical intervention. Four studies involving 93 isolated periarticular osteotomies of the first metatarsal followed up for a weighted mean of 18.6 months were identified that met the inclusion criteria. Peak dorsiflexion range of motion of the first metatarsophalangeal joint for the entire cohort of 93 patients increased 10.4 degrees . The American Orthopaedic Foot and Ankle Society Hallux Metatarsophalangeal-Interphalangeal Scoring Scale for the entire cohort of 93 patients increased 39 points from a weighted mean of 47.2 preoperatively to 86.2 postoperatively. For the two studies that included it, complete satisfaction or satisfaction with reservations was reported in only 55/75 (73.3%) patients, with the remainder being dissatisfied. A total of 21 (22.6%) procedures underwent surgical revision in the form of hardware removal (n = 8), lesser metatarsal surgery for intractable postoperative metatarsalgia (n = 7), no mention of revision procedure (n = 3), Keller resection arthroplasty (n = 2), and treatment of infection with revision of non-union (n = 1). Two studies specified the grade of hallux rigidus that underwent revision surgery after isolated periarticular osteotomy of the first metatarsal as follows: grade I, 16.7% (n = 3/18) and grade II, 30.5% (n = 18/59). Finally, a total of 30.5% (n = 18/59) of patients developed postoperative metatarsalgia or stress fracture. Additional prospective studies involving validated subjective and objective outcome measurement tools with computerized gait analysis and long-term follow-up after isolated periarticular osteotomy of the first metatarsal for the various grades of hallux rigidus, as well as with comparison with isolated cheilectomy and Valenti arthroplasty, would be beneficial. Based on the high incidence of complications until these studies can be completed, routine use of isolated periarticular osteotomy of the first metatarsal for hallux rigidus should be performed with caution or not at all. PMID- 21035042 TI - Superficial peroneal intraneural ganglion cyst originating from the inferior tibiofibular joint: the latest chapter in the book. PMID- 21035044 TI - Role of imaging in the preoperative staging of small bowel neuroendocrine tumors. AB - BACKGROUND: Imaging studies are important in the preoperative staging of patients with small bowel neuroendocrine tumors (NET) and when selecting patients for cytoreduction procedures for metastatic disease. The purpose of this study was to assess the accuracy of preoperative imaging compared with operative findings in the staging of small bowel NET. STUDY DESIGN: Sixty-four patients with small bowel NET undergoing laparotomy and who had preoperative imaging with combinations of CT, MR, and radionuclide scintigraphy were reviewed. Results of imaging studies were compared with operative findings to assess the ability of these investigations to detect mesenteric, peritoneal, and hepatic metastases. RESULTS: Mesenteric nodal metastases were seen on imaging in 47 (73%) patients and were present at laparotomy in 56 (88%) patients. Peritoneal metastases were seen on preoperative imaging in 4 (6%) patients and found at laparotomy in 16 (25%) patients. Hepatic metastases were seen on imaging in 42 patients (66%) and found at laparotomy in 49 (77%). Sensitivity and specificity for detection of hepatic metastases were 77% and 100% for CT, 82% and 100% for MR, 63% and 100% for (123)I-meta-iodobenzylguanadine scintigraphy, and 63% and 100% for (111)In octreotide. Imaging studies failed to detect hepatic metastases in 7 patients and underestimated the extent of hepatic metastatic disease in 17 patients. CONCLUSIONS: Imaging of small bowel NET, even with combinations of CT, MR, and radionuclide studies, underestimates the extent of peritoneal, mesenteric, and hepatic metastatic disease. Accurate staging of small bowel NET might be best performed at the time of laparotomy. PMID- 21035045 TI - Aneurysm-related mortality rates in the US AneuRx clinical trial. AB - BACKGROUND: The AneuRx (Medtronic) stent graft was approved by the FDA in September 1999. The purpose of this study was to ascertain the aneurysm-related mortality rate of a subgroup of the patient cohort from Medtronic's investigational premarket study. STUDY DESIGN: There were 931 study subjects, from 19 medical centers, who were followed for an average of 3.48 years. Abdominal aortic aneurysm (AAA)-related mortality rates were examined, using death certificates and medical records. RESULTS: The 1-month postimplant death rate was 1.61%. Not counting deaths related to the initial implant, there was an increase in the rate of AAA-related mortality after 3 years, from an average of 0.18% in the first 3 years to an average of 1.39% in years 4 and 5. CONCLUSIONS: Mortality in patients implanted with an AneuRx graft (as determined in this study) probably exceeds that of open procedure patients (based on medical literature) at some point in time, likely within 4 years after implant. PMID- 21035046 TI - Physicians married or partnered to physicians: a comparative study in the American College of Surgeons. AB - BACKGROUND: Dual-physician relationships are increasingly common. In this study, the authors explore how surgeons in dual-physician relationships differ from other partnered surgeons in their demographics, practice characteristics, family lives, distress, and job satisfaction. STUDY DESIGN: In 2008, members of the American College of Surgeons were asked to complete a survey that included questions on burnout, work-home conflict, and career satisfaction. RESULTS: Among 7,905 responding surgeons (a 32% response rate), 7,120 (90%) had a domestic partner (DP). Half (3,471 of 7,120 [48.8%]) of DPs did not work outside the home, 16.4% (1,165) were physicians, and 34.9% (2,484) were working nonphysicians. Surgeons whose DP was a physician were younger, newer to practice, were more likely to delay having children and to believe childrearing had slowed their career advancement, and were less likely to believe that they had enough time for their personal and family life compared with their colleagues whose DP was a working nonphysician or stayed at home (all p < 0.05). Surgeons in dual-physician relationships more often experienced a recent career conflict with their DP and a work-home conflict than surgeons whose DPs were working nonphysicians (all p < 0.0001). Surgeons whose DP is another surgeon face even greater challenges in these areas. Physicians married or partnered to another physician were more likely to have depressive symptoms and low mental quality of life than surgeons whose DP stayed at home (all p < 0.05). Surgeons whose DP stayed at home appear to be more satisfied with their career (p = 0.0006). CONCLUSIONS: Surgeons whose DP is another physicians appear to experience greater challenges balancing personal and professional life than surgeons whose DP is a working nonphysicians or whose DP stays at home. PMID- 21035047 TI - Stepwise assessment tool of operative skills (SATOS): validity testing on a porcine training model of open gastrectomy. AB - BACKGROUND: The aim of this prospective study was to evaluate and compare operative performance and technical improvement of surgical trainees learning open gastrectomy using an objective structured stepwise assessment tool of operative skills (SATOS) previously validated for open surgery. STUDY DESIGN: Thirty residents in general surgery performed 2 open partial gastrectomy training events on a porcine model. Earlier instruction was provided for the critical operative steps, with additional intraoperative instruction when required. Performance was assessed by postgraduate year (PGY) according to operative time, technical skills using a 23-step objective structured tool, and error rate. RESULTS: There were 11 PGY-3, 11 PGY-4, and 8 PGY-5 residents. At the initial assessment, performance significantly differentiated the 3 PGY grades according to technical skills and error rate. At the second assessment, all 3 PGY classes were still significantly differentiable by technical skills, with no difference in error rate. Comparing performances, residents improved operative time (p < 0.001), technical skills (p < 0.001), and error rate (p = 0.019) over the 2 training events. CONCLUSIONS: SATOS demonstrated relevant and accurate objective assessment of trainees' operative skills and improvement for open gastrectomy in a porcine model. This tool may be useful to standardize instruction, to expose weaknesses of trainees, and to determine minimal technical standards in residency programs. PMID- 21035048 TI - High case volumes and bariatric surgery outcomes. PMID- 21035050 TI - Laparoendoscopic single-site cholecystectomy: a word of concern. PMID- 21035052 TI - Critical view of safety for laparoscopic removal of difficult gallbladder. PMID- 21035054 TI - Effects of a surgical skills boot camp. PMID- 21035055 TI - A properly performed operation almost always cures chronic subareolar abscess and fistula. PMID- 21035059 TI - The impact of misinformation. PMID- 21035061 TI - Eye pain in preschool children: diagnostic and prognostic significance. AB - BACKGROUND: Preschool children often present for ophthalmologic examination because of eye pain. Although the differential diagnosis includes serious conditions, the diagnostic and prognostic importance of apparently isolated eye pain are unknown. METHODS: We reviewed records of 80 consecutive patients presenting between 2 and 6 years of age with eye pain but without a red eye or a history of an obvious cause of pain. Families of children seen in the office only once were contacted by phone to obtain follow-up information. RESULTS: Functional eye pain was diagnosed in 73 of 80 patients (91%). Of the 64 patients with follow up between 1 week to 4 years (mean, 21 months), 56 (88%) had no other cause of eye pain. Dry eyes, allergic conjunctivitis, blepharitis, corneal foreign body, sinusitis, and trichiasis were diagnosed in 7 patients. Other children were found to have refractive error, amblyopia, blepharospasm, and nystagmus--all considered unlikely to cause eye pain. CONCLUSIONS: Absent a preexisting or obvious cause of eye pain, the symptom is usually functional in preschool children who may have difficulty communicating vague visual symptoms to caregivers. However, such children deserve examination, not only so that unapparent causes can be excluded but also because unrelated conditions may require further evaluation and treatment. Parents can be reassured that if no abnormality is found on initial ophthalmologic examination, children with eye pain are unlikely to have subsequent diagnoses. PMID- 21035062 TI - Prevalence of amblyopia risk factors in congenital nasolacrimal duct obstruction. AB - PURPOSE: To determine whether children who present to an ophthalmology practice for nasolacrimal duct obstruction are more likely to have risk factors for amblyopia. METHODS: A retrospective chart review was conducted on all patients presenting to a pediatric oculoplastic specialist between January 1, 2001, and August 8, 2009. The review yielded 402 pediatric patients diagnosed with nasolacrimal duct obstruction. Children were classified as having amblyopia risk factors on the basis of the American Association for Pediatric Ophthalmology and Strabismus referral criteria. RESULTS: Of 402 patients with nasolacrimal duct obstruction, 100% received a cyclopegic refraction. Of these, 88 patients (22%) were found to have amblyogenic risk factors; 65 of these patients had amblyogenic refractive errors, 9 had strabismus, and 14 had a combination of the two. Of the 88 patients with amblyopia risk factors, 11% had a family history of strabismus compared with 9% of patients without amblyopia risk factors, which was not a statistically significant difference. There was no other significant pathology found on the dilated fundus examinations except for one child known to have persistent hyperplastic primary vitreous and a congenital cataract and one child with previously known CHARGE syndrome before the examination for nasolacrimal duct obstruction. CONCLUSIONS: Children who present with nasolacromal duct obstructions seem to be more likely to have amblyopia risk factors and therefore should have a full comprehensive pediatric ophthalmological examination, including cycloplegic refraction. PMID- 21035064 TI - Anisometropic amblyopia: axial length versus corneal curvature in children with severe refractive imbalance. AB - PURPOSE: To define the ocular parameters associated with anisometropic ambylopia in children with severe hyperopia, myopia, or astigmatism in 1 eye. METHODS: Anisometropic and fellow eyes of 13 children, ages 7-8, with anisometropia >3.0 D and amblyopia without strabismus or other visually significant ocular pathology were studied. Axial length, corneal curvature, anterior chamber depth, and corneal diameter measurements of amblyopic and fellow eyes were obtained using the IOL Master (Carl Zeiss Meditec, Dublin, CA). RESULTS: Comparing amblyopic eyes with unaffected fellow eyes as reference, patients with anisohyperopia had shorter axial lengths by an average of 1.49 mm (p = 0.001), and patients with anisomyopia had longer axial lengths by an average of 2.26 mm. Corneal astigmatism was the source of amblyogenic refractive error in 1 child. CONCLUSIONS: In children with anisometropic amblyopia, interocular differences in spherical refractive error was attributed to axial length with no differences in corneal curvature, whereas the anisoastigmatism observed in 1 case was attributed to asymmetric corneal curvature. PMID- 21035063 TI - Evaluating the burden of amblyopia treatment from the parent and child's perspective. AB - PURPOSE: To evaluate the psychometric properties of the original Parent and new Child Amblyopia Treatment Index (ATI), questionnaires that assess the burden of amblyopia treatment in children and families, and to compare scores between children treated with atropine or patching. METHODS: Parent ATI and Child ATI were administered to 233 children 7 to <13 years old and their parents as part of a randomized trial comparing patching and atropine for amblyopia treatment. For each ATI version, construct validity was assessed using factor analysis; internal consistency reliability was assessed using Cronbach's alpha. Data from the Parent ATI and Child ATI were correlated and scores for each version were compared between treatment groups. RESULTS: We analyzed the 3 subscales found in prior Parent ATI studies in younger children and confirmed subscales for adverse effects and treatment compliance, but not for social stigma, in both parent and child versions. Overall and subscale scores on the Parent ATI and Child ATI were moderately to well correlated except for the social stigma subscale. For both the Parent ATI and the Child ATI, children treated with atropine had better scores than those treated with patching, both overall and on treatment compliance and social stigma subscales (all p values <= 0.01). CONCLUSIONS: When used for children 7 to <13 years old, the Parent ATI and Child ATI have similar factor structures to each other and to the Parent ATI for children 3 to <7 years old. Atropine treatment was found to have less negative impact than patching. PMID- 21035065 TI - Adjustable suture technique for enhanced transposition surgery for extraocular muscles. AB - PURPOSE: To evaluate the results of 2 methods of vertical rectus muscle transposition surgery for sixth (abducens) nerve palsy. METHODS: Retrospective, comparative case series. Historically at our institution, transposed vertical rectus muscles were adjusted toward or attached at the adjacent corners of the lateral rectus muscle ("conventional transposition") before the development of a technique in which adjustable sutures are passed beneath the lateral rectus muscle to attach at its opposite corners ("crossed-adjustable transposition"). Comparative outcomes with these 2 techniques were analyzed in a consecutive series of sixth nerve palsy patients. RESULTS: The change from preoperative to postoperative deviation at distance was 39.3(Delta) +/- 22.7(Delta) in 23 conventional transposition cases and 48.5(Delta) +/- 27.8(Delta) in 19 crossed adjustable transposition cases, which demonstrated no statistically significant difference (p = 0.24, t-test). Simultaneous medial rectus weakening was needed less in the crossed-adjustable transposition group (37%) than in the conventional transposition group (83%), and this difference was statistically significant. (p = 0.004, Fisher exact test). CONCLUSIONS: Adjustable vertical rectus muscle transposition surgery for the management of chronic sixth nerve palsy, enhanced by passing the adjustable sutures beneath the lateral rectus muscle, requires simultaneous medial rectus muscle weakening less than half as often for satisfactory results. PMID- 21035066 TI - Effect of decreasing target oxygen saturation on retinopathy of prematurity. AB - INTRODUCTION: The authors of previous studies suggest that the oxygenation status of premature infants contributes to the development of retinopathy of prematurity (ROP). In this study we compared the incidence and severity of ROP before and after institution of a new neonatal intensive care unit oxygen protocol. METHODS: A retrospective chart review was performed of all eligible inborn patients screened for ROP during the 2 years immediately before (Group 1) to and the 2 years after (Group 2) the initiation of a new oxygen protocol. In the new protocol, target oxygen saturation was adjusted from 90%-99% to 85%-93%. Treatment criteria adhered to Early Treatment for Retinopathy of Prematurity guidelines for the study's duration. RESULTS: There were 387 infants in Group 1 and 386 infants in Group 2 (descriptive statistics adjusted for correlation due to multiple births). Mean birth weights (BWs) and gestational ages were 1,194 g and 29.2 weeks (ranges, 525-2,085 g; 23 2/7-39 6/7 weeks) for Group 1 and 1,139 g and 28.9 weeks (ranges, 520-2,500 g; 22 6/7-35 3/7 weeks) for Group 2 (p = 0.02/0.10). ROP developed in 32.7% of infants in Group 1 and 27.8% in Group 2 (p = 0.17). The incidence of ROP requiring treatment was 19.9% in Group 1 and 20.5% in Group 2 (p = 0.91). Subanalysis of infants with BW <= 1,000g (Group 1, n = 119; Group 2, n = 141) revealed ROP incidence of 75.1% versus 57.1%, respectively (p < 0.01); treatable disease occurred in 37.5% and 21.9% of affected infants (p = 0.19). CONCLUSIONS: Lowering target oxygen saturation for inborn premature infants was associated with decreased incidence of ROP only in infants with BW <= 1,000 g. Severity of disease, including need for treatment, was similar in both groups. PMID- 21035067 TI - An illuminated microcatheter for 360-degree trabeculotomy [corrected] in congenital glaucoma: a retrospective case series. AB - PURPOSE: To evaluate the efficacy of achieving a 360 degrees ab externo trabeculotomy [corrected] using an illuminated ophthalmic microcatheter for the treatment of primary congenital glaucoma. METHODS: This retrospective, consecutive case series included 16 eyes of 10 patients <= 3 years of age at the time of surgery and diagnosed with primary congenital glaucoma. All patients underwent a trabeculotomy [corrected] via microcatheter with the intent of catheterizing the full circumference of Schlemm's canal and rupturing the entire canal in a single procedure. The main outcome measure was the success rate of achieving a complete 360 degrees as compared to a partial trabeculotomy. [corrected] Secondary outcome measures included intraocular pressure (IOP), glaucoma medication usage, and adverse events. Clinical examination data are reported up to 12 months postoperatively. RESULTS: Of 16 eyes included, 12 (75%) achieved a complete 360 degrees trabeculotomy [corrected] using the microcatheter; 4 of 16 eyes (25%) achieved a partial trabeculotomy. [corrected] For all treated eyes the postoperative reduction in IOP from baseline was statistically significant at the 1-, 3-, and 6-month follow-up visits (p < 0.001). At 6 months, IOP was significantly lower in the complete as compared to the partial trabeculotomy [corrected] cohort (p = 0.03). CONCLUSIONS: A complete or partial trabeculotomy [corrected] was safely completed in eyes with primary congenital glaucoma using a microcatheter with an illuminated, atraumatic tip. PMID- 21035068 TI - Prevalence and clinical characteristics of congenital dacryocystocele. AB - OBJECTIVE: To report the prevalence, clinical findings, and outcomes in children diagnosed with congenital dacryocystocele in a well-defined population during a 20-year period. METHODS: The medical records of all Olmsted County, Minnesota, patients diagnosed with congenital dacryocystocele from January 1, 1988, through December 31, 2007, were retrospectively reviewed. RESULTS: A total of 9 children were diagnosed with dacryocystocele during the 20-year period, yielding a birth prevalence of 1 in 3,884 live births. The median age at diagnosis was 12 days (range, birth to 40 days); 7 (78%) were female. Eight patients (89%) had unilateral disease. Clinical findings included a cystic mass in all 9, dacryocystitis in 3 (33%), intranasal cysts in 3 (33%), and 1 (11%) each with facial cellulitis and dacryocystocele-induced astigmatism. Conservative treatment resolved the obstruction in 3 (33%), whereas the remaining 6 (67%) each underwent one surgery. Complete resolution was observed in all 9 patients. CONCLUSIONS: Congenital dacryocystocele is an uncommon unilateral condition of predominantly neonatal females. Clinical findings support a relatively high incidence of complications such as dacryocystitis and intranasal cysts as well as a less common finding of astigmatism that resolved without evidence of amblyopia. One third of the cases were successfully managed with conservative treatment alone; most patients required surgical intervention. PMID- 21035069 TI - Monocanalicular versus bicanalicular silicone intubation for congenital nasolacrimal duct obstruction. AB - PURPOSE: To compare the success rate of monocanalicular versus bicanalicular silicone intubation of the nasolacrimal duct for congenital nasolacrimal duct obstruction (CNLDO). METHODS: In a prospective randomized clinical trial, 70 eyes of 57 children with CNLDO underwent either monocanalicular silicone intubation (MCI) (n = 35 eyes) or bicanalicular silicone intubation (BCI) (n = 35 eyes). All procedures were performed by 1 oculoplastic surgeon. Tube removal was planned for 3 months postoperatively. The results were assessed using a Munk score. Treatment success was defined as Munk score 0-1 at 3 months after tube removal. RESULTS: The surgical outcome was assessed in 29 eyes with MCI and 27 eyes with BCI. The mean age of treatment was 34.9 +/- 12.7 months for MCI and 38.7 +/- 18.6 months for BCI. Treatment success was achieved in 25 of 29 eyes (86.2%; 95% CI, 79%-96%) in the MCI group compared with 24 of 27 eyes (89%; 95% CI, 84%-94%) in the BCI group (RR = 0.96; 95% CI, 0.79-1.18). There were no corneal or canalicular complications in either group. CONCLUSIONS: MCI and BCI were successful in a similar percentage of children with CNLDO. The mainadvantage of the former technique was easy tube removal without sedation in the office. PMID- 21035070 TI - Thyroid eye disease: honing your skills to improve outcomes. AB - Thyroid eye disease affects the eyelids, orbital compartment, and extraocular muscles, resulting in a highly variable degree of chemosis and enlargement of the preorbital fat pads, eyelid retraction, proptosis, restrictive strabismus, torticollis, and, rarely, compressive or congestive optic neuropathy. Although most patients with thyroid eye disease are best treated conservatively, those more severely affected may benefit from orbital decompression, strabismus surgery, or eyelid retraction repair after stabilization has occurred. Botulinum A toxin, high-dose intravenous corticosteroids, and radiation treatment are therapeutic options in select cases. Compressive or congestive optic neuropathy and severe corneal exposure warrant consideration of surgical intervention on an urgent basis without waiting for stabilization. Epidemiology and risks and benefits of high-dose steroids and radiation therapy are reviewed along with recommendations to improve conservative as well as surgical management of this disease. Strategies to manage strabismus and optimize outcomes are provided. PMID- 21035071 TI - Spectral domain optical coherence tomographic characteristics of unilateral peripapillary myelinated retinal nerve fibers involving the macula. AB - Unilateral, peripapillary, retinal nerve fiber myelination involving the macula, with optic disk hypoplasia, myopia, and amblyopia, is rare. We performed spectral domain optical coherence tomographic findings in 2 patients with this condition. Both patients had normal foveal morphology, reduced retinal thickness in the same distribution as the myelination, and optic nerve hypoplasia. PMID- 21035072 TI - Bilateral sectoranopia caused by bilateral geniculate body infarction in a 14 year-old boy with inflammatory bowel disease. AB - Bilateral lesions of the lateral geniculate bodies are rare and produce unusual field defects that can be predicted on the basis of their vascular anatomy. We report a rare case of bilateral sectoranopic visual field defects caused by bilateral infarction of the lateral geniculate nucleus in a 14-year-old boy with inflammatory bowel disease and recurrent pancreatitis. PMID- 21035073 TI - Bilateral choroidal osteoma with optic atrophy. AB - Choroidal osteoma is a rare, yellowish-white lesion of the choroid that predominantly affects young women in the second decade of life. Subretinal neovascularization or collection of subretinal fluid may occur in 50 % or more patients in the long run. A 15-year-old girl presented to our practice with bilateral choroidal osteoma associated with advanced bilateral optic atrophy. The underlying cause for optic atrophy is unclear; possible explanations include mechanical pressure effect and ischemic damage. PMID- 21035074 TI - Toxic anterior segment syndrome after pediatric cataract surgery. AB - Toxic anterior segment syndrome is an acute, sterile, anterior segment inflammation that occurs after any anterior segment surgery. The condition is an increasingly recognized complication of adult cataract surgery. Here we report the clinical findings of a case of toxic anterior segment syndrome in a child after uneventful congenital cataract surgery. PMID- 21035075 TI - Silent sinus syndrome causing cyclovertical diplopia masquerading as superior oblique paresis in the fellow eye. AB - Silent sinus syndrome is an insidious maxillary sinus inflammatory disease causing a lowering, thinning, or even absorption of the orbital floor. Patients usually present with progressive enophthalmos and hypoglobus. We report a 41-year old man with silent sinus syndrome who presented with cyclovertical diplopia masquerading as superior oblique muscle paresis in the fellow eye. Inferior oblique myectomy in the fellow eye resulted in excellent alignment. PMID- 21035076 TI - Proliferative retinopathy in a child with congenital cyanotic heart disease. AB - In congenital cyanotic heart disease, oxygenated and deoxygenated blood mixes, and oxygen saturation of the arterial blood is not maintained. As a result, an ischemic environment prevails in the entire body. While various ocular findings have been described in patients with cyanotic heart disease, proliferative retinopathy has not been previously noted. We report a child with congenital cyanotic heart disease and multiple fibrovascular fronds over the fundus consistent with proliferative retinopathy. PMID- 21035077 TI - Delayed-onset retinal detachment after an intravitreal injection of ranibizumab for zone 1 plus retinopathy of prematurity. AB - Intravitreal injection of bevacizumab has been shown to satisfactorily treat retinopathy of prematurity; nevertheless, the safety of antivascular endothelial growth factor therapy in children remains uncertain. We report a patient with bilateral, zone 1, stage 3 plus retinopathy of prematurity who was treated with combined laser photocoagulation and intravitreal ranibizumab injection and demonstrated full regression at 3 months after injection but then developed bilateral retinal detachments 1 month later. PMID- 21035078 TI - Isolated abducens nerve palsy in a patient with scrub typhus. AB - Abducens nerve palsies associated with infectious diseases are infrequent. Scrub typhus is an acute, febrile, infectious illness caused by Orientia tsutsugamushi (formerly Rickettsia tsutsugamushi), an obligate-intracellular gram-negative bacterium. The organism has been reported to be capable of entering the nervous system, causing meningitis and focal neurologic abnormalities. We report a case of isolated abducens nerve palsy associated with a scrub typhus infection. PMID- 21035079 TI - Occipital porencephaly in a child with gyrate atrophy of the choroid and retina. AB - A 4-year-old girl was hospitalized for psychomotor delay, low vision, and horizontal nystagmus. She was found to have bilateral chorioretinal atrophic scars and 2 large occipital porencephalic cavities. High plasma ornithine levels led to the presumed diagnosis of gyrate atrophy of the choroid and retina. After 6 months of arginine-restricted diet and high-dose pyridoxine (300 mg/d), there was no change of plasma ornithine level or ocular findings. To our knowledge, this is the first report showing an association of porencephaly with gyrate atrophy of the choroid and retina. PMID- 21035080 TI - What are the spondyloarthropathies? PMID- 21035081 TI - Update on the genetics of spondyloarthritis--ankylosing spondylitis and psoriatic arthritis. AB - Spondyloarthritis refers to a group of inflammatory rheumatic diseases that share common clinical and genetic characteristics. Due to the rapid advances in technology and computational genetics, there is now an increasing list of well validated genes in spondyloarthritis. The newest genetic associations are of modest magnitude and have been identified as a result of analysing thousands of samples, using genome-wide association scans or targeted candidate-gene association studies. In this article, we will highlight the genes associated with spondyloarthritis, with an emphasis on the recent candidate genes that have been identified in ankylosing spondylitis and psoriatic arthritis. If applicable, we will also discuss their potential relevance to the clinical rheumatologist. PMID- 21035082 TI - Classification criteria for psoriatic arthritis and ankylosing spondylitis/axial spondyloarthritis. AB - The concept of spondyloarthritides (or spondyloarthropathies, SpAs) that comprises a group of interrelated disorders has been recognised since the early 1970s. While the European Spondyloarthropathy Study Group (ESSG) criteria and the Amor criteria have been developed to embrace the entire group of SpAs, new criteria for psoriatic arthritis have been developed recently. The Classification of Psoriatic Arthritis (CASPAR) study, a large one of more than 1000 patients, led to a new set of validated classification criteria for psoriatic arthritis. Since their publication in 2006 the CASPAR criteria are widely used in clinical studies. In ankylosing spondylitis, the 1984 modified New York criteria have been used widely in clinical studies and daily practice but are not applicable in early disease when the characteristic radiographical signs of sacroiliitis are not visible but active sacroiliitis is readily detectable by magnetic resonance imaging (MRI). This led to the concept of axial SpA that includes patients with and without radiographical damage; candidate criteria for axial SpA were developed based on proposals for a structured diagnostic approach. These criteria were validated in the Assessment of Spondyloarthritis International Society (ASAS) study on new classification criteria for axial SpA, a large international prospective study. In this new criteria, sacroiliitis showing up on MRI has been given as much weight as sacroiliitis on radiographs, thereby also identifying patients with early axial SpA. Both the CASPAR and the ASAS criteria for axial SpA are likely to be of use as diagnostic criteria. PMID- 21035083 TI - Measurement: function and mobility (focussing on the ICF framework). AB - While several instruments and measures are available to assess function and mobility, there was no exhaustive list of impairments, limitations and restrictions that are the consequence of ankylosing spondylitis (AS). The International Classification of Functioning, Disability and Health (ICF) facilitates agreement on a comprehensive description of aspects of functioning that are relevant and typical for a specific disease by using ICF categories. The Comprehensive ICF Core Set for AS is the selection of 80 ICF categories that are typical and relevant for AS. Physical functioning and mobility have an essential but partial role in the broad view of functioning and health in AS. Consistent with the bio-psycho-social model, the ICF Core Set for AS also recognises the role of contextual factors, either environmental or personal, when understanding functioning. This new reference for functioning is now available for clinical practice and research. It can help to increase insight into the complexity of functioning and can serve as the starting point for the development of new instruments that address either global functioning or aspects of functioning. PMID- 21035084 TI - Are current available therapies disease-modifying in spondyloarthritis? AB - Disease modification in spondyloarthritis should target the improvement of symptoms and preservation of function. Therefore, inhibition of structural damage caused by the disease processes appears essential. In spondyloarthritis, structural damage results mainly in progressive ankylosis of the spine and peripheral joint destruction. Currently available therapies for the treatment of spondyloarthritis appear effective at inhibiting tissue destruction but, with the exception of celecoxib, do not appear to affect new tissue formation leading to ankylosis. In this article, we discuss clinical and pathophysiological concepts of disease modification in spondyloarthritis, challenges in its evaluation, recent clinical data and new concepts that may help explain structural damage as well as the onset and progression of disease. PMID- 21035085 TI - Magnetic resonance imaging in spondyloarthritis--how to quantify findings and measure response. AB - Sensitive and reliable tools for monitoring disease activity and damage, and for prognostication, are essential in the management of patients with spondyloarthritis, including ankylosing spondylitis and psoriatic arthritis. Magnetic resonance imaging (MRI) allows direct visualisation of inflammation in peripheral and axial joints, and peripheral and axial entheses, and has dramatically improved the possibilities for early diagnosis and objective monitoring of the disease process in spondyloarthritis. Truthful, discriminative and feasible scoring systems are available for the assessment of inflammatory activity in the spine and sacroiliac joints in axial spondyloarthritis and in the hands of patients with peripheral psoriatic arthritis. Various systems for assessment of damage in axial and peripheral joints are available, but further studies are needed to document their value in clinical trials and clinical practice. The present article reviews key aspects of the status and recent important advances in MRI in spondyloarthritis, focussing on available MRI tools for assessing activity and damage in peripheral and, particularly, axial joints. PMID- 21035086 TI - Disease measurement--enthesitis, skin, nails, spine and dactylitis. AB - Outcome measurement is a key part of study design but presents particular challenges in spondyloarthropathy. Enthesitis and dactylitis are typical features of spondyloarthropathy and validated scoring systems for both are available, although the majority of enthesitis outcome measures are validated in ankylosing spondylitis (AS) only. Assessment of axial disease is well researched in AS and composite outcome measures are routinely used. However, assessment of axial disease in predominantly peripheral arthritis, such as psoriatic arthritis, is problematic and under-researched. Extensive research in dermatology has provided multiple outcome measures for skin psoriasis. The psoriasis area and severity index (PASI) remains the most common outcome measure used, despite the fact that significant problems exist with this scale and that newer scoring methods and modifications of the PASI show better validity. Nail psoriasis is accurately measured by detailed scoring systems but these can be time-consuming. PMID- 21035087 TI - Soluble and tissue biomarkers in ankylosing spondylitis. AB - The study of biomarkers has become a very important field of research in spondyloarthropathy. Biomarkers are useful for different aspects of the disease such as diagnosis, assessment of disease activity and outcome, including damage. The most commonly used biomarkers in spondyloarthropathies are HLA-B27 for diagnosis and erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) for disease activity. HLA-B27 is very sensitive but has a low specificity. ESR and CRP have both low sensitivity and specificity. The introduction of new and very expensive therapies is another reason for analysis of biomarkers. Clinicians need tools to predict more accurately disease activity, disease progression and response to therapy. This article focusses on the several known and new biomarkers of promise, including markers for cartilage and bone damage, and discusses some of the problems encountered during the search and development of new biomarkers. Biomarkers, soluble and tissue-related, reflecting structural damage and disease activity, constitute a high priority for the drug discovery process and the understanding of the pathogenesis of a particular disease. The identification of relevant tools to evaluate the natural course, disease activity, treatment response and outcome of ankylosing spondylitis is of increasing relevance since the raised awareness and development of new therapeutic options. Until now these different aspects are monitored by artificial patient-centred or physician-centred constructs. Very often, their approach is indirect and is not free from disease-unrelated influences. The Outcome Measures in Rheumatology Soluble Biomarker Working Group has taken several major steps towards the development and implementation of such assessment methods. The major drawback is that these tools do not directly reflect biological and pathological processes. Serological biomarkers objectively measure different aspects of the biological and pathological process and may contribute to a major advance in the assessments of patients. The ultimate goal is the use of biomarkers in a personalised approach for disease management in clinical practice. PMID- 21035088 TI - Therapeutic considerations in spondyloarthritis patients who fail tumour necrosis factor antagonists. AB - The tumour necrosis factor (TNF) antagonists have significantly improved quality of life and functional status in patients with spondyloarthritis (SpA). The excitement regarding the remarkable success of these agents is justified but challenges remain. In particular, alternative systemic therapies with proven efficacy for patients who fail TNF antagonists have been developed in rheumatoid arthritis but are not yet available in SpA. In this article, the approach to patients with psoriatic arthritis (PsA) or ankylosing spondylitis (AS) who fail TNF antagonists will be discussed with the goal of providing a path to the clinician, who must manage these patients amidst uncertainty. Three central questions will be addressed. Why does a particular SpA patient not respond to a TNF antagonist? How can the clinician improve the probability of treatment response in patients who fail a TNF antagonist? What specific approaches can be taken to control disease activity in PsA or AS following treatment failure with a TNF antagonist? Data from controlled trials, registries and pilot studies will be combined with expert opinion to address these important questions. PMID- 21035089 TI - Ultrasound imaging in spondyloarthropathies. AB - Through recent technological advances, ultrasound allows high-resolution visualisation of inflammatory and destructive changes in tendon and joint structures. Over the last few years, the added value of the use of ultrasound for evaluating entheseal involvement in spondyloarthritis (SpA) patients has been demonstrated. Several studies have described the ultrasound features of enthesitis in SpA, revealing the high frequency of clinically asymptomatic abnormal findings. It is, therefore, highly relevant to consider the validity of ultrasonographic measures of entheseal inflammation and damage. This article focusses on ultrasound appearance of peripheral enthesitis, and underlines the advantages and current limitations of the technique for the management of SpA. PMID- 21035090 TI - Bacterial agents in spondyloarthritis: a destiny from diversity? AB - The spondyloarthritides (SpAs) are a group of diseases that share clinical, radiographic and laboratory features; these arthritides also display a tendency for family aggregation. Given the intimate relationship that these types of arthritis share, it suggests that the SpAs might share a common aetiology. Of all the SpAs, the role of bacteria is most clearly defined in reactive arthritis. Tremendous recent insights into the pathophysiology of reactive arthritis have been made, demonstrating that the causative bacteria play a much more complex role than previously thought. The bacteria that are proven to cause reactive arthritis, one of the five types of SpA, will be reviewed and their role in the pathophysiology of reactive arthritis will be examined. The speculative data suggesting links between various other bacteria and the other types of SpAs will be critically analysed. Although these data are not definitive, when viewed using the paradigm that the SpAs might actually represent a common end point from several diverse starting points, they are provocative, suggesting that bacteria might, indeed, be aetiological for the entire group of SpAs. PMID- 21035091 TI - Investigation of involved tissue in axial spondyloarthritis--what have we learnt from immunohistochemical studies? AB - The principal clinical and radiological feature of all axial spondyloarthritis is an involvement of the axial skeleton (sacroiliac joints and spine) and, to a lesser extent, the hip joints. Immunohistochemical studies provide worthwhile information regarding disease mechanisms in axial spondyloarthritis. Immunohistochemical investigation of sacroiliac joints, spine and hip joints suggested an important role of T-cells in the development of acute inflammatory lesions. Furthermore, activated angiogenesis and macrophage/osteoclast activation also play a relevant role in the development of early active inflammatory lesions. Nonetheless, the mechanisms leading to activation of osteoproliferation with subsequent syndesmophyte and ankylosis formation in patients with spondyloarthritis remains unclear. It is suggested that the Wnt pathway is actively involved in this process due to decreased expression of new bone formation inhibitors such as sclerostin. However, to understand the full picture of the interrelationship between inflammation and new bone formation, and to explore new treatment targets for suppression of the excessive bone formation as well, further investigations are needed. PMID- 21035092 TI - Toward understanding genetic mechanisms of complex traits in rice. AB - Rice is the primary carbohydrate staple cereal feeding the world population. Many genes, known as quantitative trait loci (QTLs), control most of the agronomically important traits in rice. The identification of QTLs controlling agricultural traits is vital to increase yield and meet the needs of the increasing human population, but the progress met with challenges due to complex QTL inheritance. To date, many QTLs have been detected in rice, including those responsible for yield and grain quality; salt, drought and submergence tolerance; disease and insect resistance; and nutrient utilization efficiency. Map-based cloning techniques have enabled scientists to successfully fine map and clone approximately seventeen QTLs for several traits. Additional in-depth functional analyses and characterizations of these genes will provide valuable assistance in rice molecular breeding. PMID- 21035093 TI - A nuclear-encoded mitochondrial gene AtCIB22 is essential for plant development in Arabidopsis. AB - Complex I (the NADH:ubiquinone oxidoreductase) of the mitochondrial respiratory chain is a complicated, multi-subunit, membrane-bound assembly and contains more than 40 different proteins in higher plants. In this paper, we characterize the Arabidopsis homologue (designated as AtCIB22) of the B22 subunit of eukaryotic mitochondrial Complex I. AtCIB22 is a single-copy gene and is highly conserved throughout eukaryotes. AtCIB22 protein is located in mitochondria and the AtCIB22 gene is widely expressed in different tissues. Mutant Arabidopsis plants with a disrupted AtCIB22 gene display pleiotropic phenotypes including shorter roots, smaller plants and delayed flowering. Stress analysis indicates that the AtCIB22 mutants' seed germination and early seedling growth are severely inhibited by sucrose deprivation stress but more tolerant to ethanol stress. Molecular analysis reveals that in moderate knockdown AtCIB22 mutants, genes including cell redox proteins and stress related proteins are significantly up-regulated, and that in severe knockdown AtCIB22 mutants, the alternative respiratory pathways including NDA1, NDB2, AOX1a and AtPUMP1 are remarkably elevated. These data demonstrate that AtCIB22 is essential for plant development and mitochondrial electron transport chains in Arabidopsis. Our findings also enhance our understanding about the physiological role of Complex I in plants. PMID- 21035094 TI - Identification and expression analysis of mical family genes in zebrafish. AB - Mical (molecule interacting with CasL) represent a conserved family of cytosolic multidomain proteins that has been shown to be associated with a variety of cellular processes, including axon guidance, cell movement, cell-cell junction formation, vesicle trafficking and cancer cell metastasis. However, the expression and function of these genes during embryonic development have not been comprehensively characterized, especially in vertebrate species, although some limited in vivo studies have been carried out in neural and musculature systems of Drosophila and in neural systems of vertebrates. So far, no mical family homologs have been reported in zebrafish, an ideal vertebrate model for the study of developmental processes. Here we report eight homologs of mical family genes in zebrafish and their expression profiles during embryonic development. Consistent with the findings in Drosophila and mammals, most zebrafish mical family genes display expression in neural and musculature systems. In addition, five mical homologs are detected in heart, and one, micall2a, in blood vessels. Our data established an important basis for further functional studies of mical family genes in zebrafish, and suggest a possible role for mical genes in cardiovascular development. PMID- 21035095 TI - Faster evolution of Z-linked duplicate genes in chicken. AB - It has been shown that duplicate genes on the X chromosome evolve much faster than duplicate genes on autosomes in Drosophila melanogaster. However, whether this phenomenon is general and can be applied to other species is not known. Here we examined this issue in chicken that have heterogametic females (females have ZW sex chromosome). We compared sequence divergence of duplicate genes on the Z chromosome with those on autosomes. We found that duplications on the Z chromosome indeed evolved faster than those on autosomes and show distinct patterns of molecular evolution from autosomal duplications. Examination of the expression of duplicate genes revealed an enrichment of duplications on the Z chromosome having male-biased expression and an enrichment of duplications on the autosomes having female-biased expression. These results suggest an evolutionary trend of the recruitment of duplicate genes towards reproduction-specific function. The faster evolution of duplications on Z than on the autosomes is most likely contributed by the selective forces driving the fixation of adaptive mutations on Z. Therefore, the common phenomena observed in both flies and chicken suggest that duplicate genes on sex chromosomes have distinct dynamics and are more influenced by natural selection than autosomal duplications, regardless of the kind of sex determination systems. PMID- 21035096 TI - Expression of CENH3 alleles in synthesized allopolyploid Oryza species. AB - Synthesized allopolyploids are valuable materials for comparative analyses of two or more distinct genomes, such as the expression changes (activation, inactivation or differential expression) of orthologous genes following allopolyploidization. CENH3 is a centromere- specific histone H3 variant and has been regarded as a central component in kinetochore formation and centromere function. In this study, interspecific hybrids of Oryza genus (AA * CC, AA * CCDD) and their backcross progenies were produced, and the genome constitutions were identified as AC, ACC, ACD, AACD, or AA(CD) by Genomic in situ hybridization (GISH). We further cloned and sequenced the CENH3 genes from O. sativa (AA), O. officinalis (CC) and O. latifolia (CCDD). Sequencing of RT-PCR products revealed that CENH3_C2 and CENH3_D, the two CENH3 alleles from O. latifolia, showed polymorphism in several sites, while CENH3_C2 and CENH3_C1 from O. officinalis were different at only two amino acids positions. Moreover, we found that the CENH3 genes from both parents are expressed in interspecific hybrids and their progenies. Specifically, based on our cDNA sequencing data, the ratio of expression level between CENH3_A and CENH3_C1 was approximately 1 in AC and 0.5 in ACC genomes, respectively. As a result, the CENH3 expression patterns shed more light on the inter-coordination between varied centromeric DNA sequences and highly conserved kinetochore protein in synthesized allopolyploids of Oryza genus. PMID- 21035097 TI - Cell and molecular biology of microtubule plus end tracking proteins: end binding proteins and their partners. AB - The microtubule plus end is a crucial site for the regulation of microtubule dynamics and microtubule association with different cellular organelles and macromolecular complexes. Several evolutionarily conserved groups of proteins form comet-like accumulations at the growing microtubule plus ends. These proteins belong to functionally diverse and structurally unrelated families: they include motors, nonmotor proteins, microtubule polymerases, and depolymerases as well as regulatory and adaptor proteins. Here, we provide an overview of microtubule plus end binding proteins, describe what is known about the mechanisms of their association with growing microtubule tips, and discuss their functional properties in relation to microtubule plus end accumulation. PMID- 21035098 TI - New insights into the roles of molecular chaperones in Chlamydomonas and Volvox. AB - The unicellular green alga Chlamydomonas reinhardtii has been used as a model organism for many decades, mainly to study photosynthesis and flagella/cilia. Only recently, Chlamydomonas has received much attention because of its ability to produce hydrogen and nonpolar lipids that have promise as biofuels. The best studied multicellular cousin of Chlamydomonas reinhardtii is Volvox carteri, whose life cycle comprises events that have clear parallels in higher plants and/or animals, making it an excellent system in which to study fundamental developmental processes. Molecular chaperones are proteins that guide other cellular proteins through their life cycle. They assist in de novo folding of nascent chains, mediate assembly and disassembly of protein complexes, facilitate protein transport across membranes, disassemble protein aggregates, fold denatured proteins back to the native state, and transfer unfoldable proteins to proteolytic degradation. Hence, molecular chaperones regulate protein function under all growth conditions and play important roles in many basic cellular and developmental processes. The aim of this chapter is to describe recent advances toward understanding molecular chaperone biology in Chlamydomonas and Volvox. PMID- 21035099 TI - Unique functions of repetitive transcriptomes. AB - Repetitive sequences occupy a huge fraction of essentially every eukaryotic genome. Repetitive sequences cover more than 50% of mammalian genomic DNAs, whereas gene exons and protein-coding sequences occupy only ~3% and 1%, respectively. Numerous genomic repeats include genes themselves. They generally encode "selfish" proteins necessary for the proliferation of transposable elements (TEs) in the host genome. The major part of evolutionary "older" TEs accumulated mutations over time and fails to encode functional proteins. However, repeats have important functions also on the RNA level. Repetitive transcripts may serve as multifunctional RNAs by participating in the antisense regulation of gene activity and by competing with the host-encoded transcripts for cellular factors. In addition, genomic repeats include regulatory sequences like promoters, enhancers, splice sites, polyadenylation signals, and insulators, which actively reshape cellular transcriptomes. TE expression is tightly controlled by the host cells, and some mechanisms of this regulation were recently decoded. Finally, capacity of TEs to proliferate in the host genome led to the development of multiple biotechnological applications. PMID- 21035100 TI - Experience dependent changes in odour-viscosity perception. AB - One consequence of experiencing flavour - the combination of taste, smell and somatosensation that occurs during ingestion - is that it can result in perceptual changes for the odour component, when this is later smelled alone. One such change is the acquisition of taste-like properties, but whether odours can also acquire somatosensory-like qualities is largely unknown. Participants here were exposed to one odour sampled in a viscous solution, another sampled in a sweet/viscous solution, and a further odour sampled in water. The odour sampled in the sweet/viscous solution was, when later sniffed alone, judged to smell thicker and sweeter, than the other two odours. Similarly, when the sweet/viscous paired odour was added to a viscous solution, the combination was judged as more viscous, than the other two odours - and sweeter when added to a sweet solution. This experiment suggests that odours can acquire tactile-like somatosensory qualities and this may best occur when a taste is present during learning. Recent work indicates that tastes may be superior to somatosensory stimuli alone in promoting flavour binding, a seeming precondition for this type of learning. PMID- 21035101 TI - The environmental applications of activated carbon/zeolite composite materials. AB - Over the past couple of years, the resurgence of placing an effective and sustainable amendment to combat against the auxiliary industrial entities, remains a highly contested agenda from a global point. With the renaissance of activated carbon, there has been a steadily growing interest in the research field. Recently, the adoption of zeolite composite, a prestigious advanced catalyst which formulates the enhancement of adsorption rate and hydrogen storage capability, has fore fronted to be a new growing branch in the scientific community. Confirming the assertion, this paper presents a state of art review of activated carbon/zeolite composite technology, its fundamental background studies, and environmental implications. Moreover, its major challenges together with the future expectation are summarized and discussed. Conclusively, the expanding of activated carbon/zeolite composite represents a potentially viable and powerful tool, leading to the plausible improvement of environmental preservation. PMID- 21035102 TI - Hyperchlorhidrosis caused by homozygous mutation in CA12, encoding carbonic anhydrase XII. AB - Excessive chloride secretion in sweat (hyperchlorhidrosis), leading to a positive sweat test, is most commonly indicative of cystic fibrosis yet is found also in conjunction with various metabolic, endocrine, and dermatological disorders. There is conflicting evidence regarding the existence of autosomal-recessive hyperchlorhidrosis. We now describe a consanguineous Israeli Bedouin kindred with autosomal-recessive hyperchlohidrosis whose sole symptoms are visible salt precipitates after sweating, a preponderance to hyponatremic dehydration, and poor feeding and slow weight gain at infancy. Through genome-wide linkage analysis, we demonstrate that the phenotype is due to a homozygous mutation in CA12, encoding carbonic anhydrase XII. The mutant (c.427G>A [p.Glu143Lys]) protein showed 71% activity of the wild-type enzyme for catalyzing the CO2 hydration to bicarbonate and H(+), and it bound the clinically used sulfonamide inhibitor acetazolamide with high affinity (K(I) of 10 nM). Unlike the wild-type enzyme, which is not inhibited by chloride, bromide, or iodide (K(I)s of 73-215 mM), the mutant is inhibited in the submicromolar range by these anions (K(I)s of 0.37-0.73 mM). PMID- 21035103 TI - Fibrochondrogenesis results from mutations in the COL11A1 type XI collagen gene. AB - Fibrochondrogenesis is a severe, autosomal-recessive, short-limbed skeletal dysplasia. In a single case of fibrochondrogenesis, whole-genome SNP genotyping identified unknown ancestral consanguinity by detecting three autozygous regions. Because of the predominantly skeletal nature of the phenotype, the 389 genes localized to the autozygous intervals were prioritized for mutation analysis by correlation of their expression with known cartilage-selective genes via the UCLA Gene Expression Tool, UGET. The gene encoding the alpha1 chain of type XI collagen (COL11A1) was the only cartilage-selective gene among the three candidate intervals. Sequence analysis of COL11A1 in two genetically independent fibrochondrogenesis cases demonstrated that each was a compound heterozygote for a loss-of-function mutation on one allele and a mutation predicting substitution for a conserved triple-helical glycine residue on the other. The parents who were carriers of missense mutations had myopia. Early-onset hearing loss was noted in both parents who carried a loss-of-function allele, suggesting COL11A1 as a locus for mild, dominantly inherited hearing loss. These findings identify COL11A1 as a locus for fibrochondrogenesis and indicate that there might be phenotypic manifestations among carriers. PMID- 21035104 TI - Prodynorphin mutations cause the neurodegenerative disorder spinocerebellar ataxia type 23. AB - Spinocerebellar ataxias (SCAs) are dominantly inherited neurodegenerative disorders characterized by progressive cerebellar ataxia and dysarthria. We have identified missense mutations in prodynorphin (PDYN) that cause SCA23 in four Dutch families displaying progressive gait and limb ataxia. PDYN is the precursor protein for the opioid neuropeptides, alpha-neoendorphin, and dynorphins A and B (Dyn A and B). Dynorphins regulate pain processing and modulate the rewarding effects of addictive substances. Three mutations were located in Dyn A, a peptide with both opioid activities and nonopioid neurodegenerative actions. Two of these mutations resulted in excessive generation of Dyn A in a cellular model system. In addition, two of the mutant Dyn A peptides induced toxicity above that of wild type Dyn A in cultured striatal neurons. The fourth mutation was located in the nonopioid PDYN domain and was associated with altered expression of components of the opioid and glutamate system, as evident from analysis of SCA23 autopsy tissue. Thus, alterations in Dyn A activities and/or impairment of secretory pathways by mutant PDYN may lead to glutamate neurotoxicity, which underlies Purkinje cell degeneration and ataxia. PDYN mutations are identified in a small subset of ataxia families, indicating that SCA23 is an infrequent SCA type (~0.5%) in the Netherlands and suggesting further genetic SCA heterogeneity. PMID- 21035105 TI - SOBP is mutated in syndromic and nonsyndromic intellectual disability and is highly expressed in the brain limbic system. AB - Intellectual disability (ID) affects 1%-3% of the general population. We recently reported on a family with autosomal-recessive mental retardation with anterior maxillary protrusion and strabismus (MRAMS) syndrome. One of the reported patients with ID did not have dysmorphic features but did have temporal lobe epilepsy and psychosis. We report on the identification of a truncating mutation in the SOBP that is responsible for causing both syndromic and nonsyndromic ID in the same family. The protein encoded by the SOBP, sine oculis binding protein ortholog, is a nuclear zinc finger protein. In mice, Sobp (also known as Jxc1) is critical for patterning of the organ of Corti; one of our patients has a subclinical cochlear hearing loss but no gross cochlear abnormalities. In situ RNA expression studies in postnatal mouse brain showed strong expression in the limbic system at the time interval of active synaptogenesis. The limbic system regulates learning, memory, and affective behavior, but limbic circuitry expression of other genes mutated in ID is unusual. By comparing the protein content of the +/jc to jc/jc mice brains with the use of proteomics, we detected 24 proteins with greater than 1.5-fold differences in expression, including two interacting proteins, dynamin and pacsin1. This study shows mutated SOBP involvement in syndromic and nonsyndromic ID with psychosis in humans. PMID- 21035106 TI - MASP1 mutations in patients with facial, umbilical, coccygeal, and auditory findings of Carnevale, Malpuech, OSA, and Michels syndromes. AB - Distinctive facial features consisting of hypertelorism, telecanthus, blepharophimosis, blepharoptosis, epicanthus inversus, periumbilical defects, and skeletal anomalies are seen in autosomal-recessive Carnevale, Malpuech, Michels, and oculo-skeletal-abdominal (OSA) syndromes. The gene or genes responsible for these syndromes were heretofore unknown. We report on three individuals from two consanguineous Turkish families with findings characteristic of these syndromes, including facial dysmorphism, periumbilical depression, mixed hearing loss, radioulnar synostosis, and coccygeal appendage. Homozygosity mapping yielded an autozygous region on chromosome 3q27 in both families. In one family, whole exome sequencing revealed a missense mutation, MASP1 c.2059G>A (p.G687R), that cosegregated with the phenotype. In the second family, Sanger sequencing of MASP1 revealed a nonsense mutation, MASP1 c.870G>A (p.W290X), that also cosegregated with the phenotype. Neither mutation was found in 192 Turkish controls or 1200 controls of various other ancestries. MASP1 encodes mannan-binding lectin serine protease 1. The two mutations occur in a MASP1 isoform that has been reported to process IGFBP-5, thereby playing a critical role in insulin growth factor availability during craniofacial and muscle development. These results implicate mutations of MASP1 as the cause of a human malformation syndrome and demonstrate the involvement of MASP1 in facial, umbilical, and ear development during the embryonic period. PMID- 21035107 TI - Perception of products by progressive multisensory integration. A study on hammers. AB - The aim of this work is to determine the influence of multisensory (visual haptic) integration and the level of interaction (seeing photographs, seeing the actual product, touching it and using it) on the perception of products, including perceived ergonomics. The product selected for the experiment was the hammer, as this will help to establish whether emotional design studies can also apply to 'commercial' products. Subjective opinions of users were evaluated through semantic differential tests. A factor analysis identified six semantic factors or axes (Quality/Robustness, Ergonomics/Appearance, Innovation, Lightness, Dynamic Effects, and Efficacy). Results show that Lightness and Dynamic Effects are quite sensitive to the level of interaction, while Ergonomics/Appearance is partially affected. However, the perceptions of Innovation, Quality/Robustness and Efficacy are not so affected and they could be detected through a lower level of interaction (i.e. seeing photographs). This suggests that commercial products seem sensitive to emotional design studies and that multisensory integration enhances the perception of the factors that are clearly linked with physical interaction between users and tools, i.e. Ergonomics/Appearance, Lightness and Dynamic Effects. Additionally, it should be highlighted that some aspects related with the ergonomics and ease of use of products are also perceived at different stages of interaction. PMID- 21035108 TI - Immunohistochemical expression of mast cell tryptase in giant cell fibroma and inflammatory fibrous hyperplasia of the oral mucosa. AB - This study analysed the immunohistochemical expression of mast cell tryptase in giant cell fibromas (GCFs). In addition, the possible interaction of mast cells with stellate giant cells, as well as their role in fibrosis and tumour progression, was investigated. For this purpose, the results were compared with cases of inflammatory fibrous hyperplasia (IFH) and normal oral mucosa. Thirty cases of GCF, 30 cases of IFH and 10 normal mucosa specimens used as control were selected. Immunoreactivity of mast cells to the anti-tryptase antibody was analysed quantitatively in the lining epithelium and in connective tissue. In the epithelial component (p=0.250) and connective tissue (p=0.001), the largest mean number of mast cells was observed in IFHs and the smallest mean number in GCFs. In connective tissue, the mean percentage of degranulated mast cells was higher in GCFs than in IFHs and normal mucosa specimens (p<0.001). Analysis of the percentage of degranulated mast cells in areas of fibrosis and at the periphery of blood vessels also showed a larger mean number in GCFs compared to IFHs and normal mucosa specimens (p<0.001). The percent interaction between mast cells and stellate giant cells in GCFs was 59.62%. In conclusion, although mast cells were less numerous in GCFs, the cells exhibited a significant interaction with stellate giant cells present in these tumours. In addition, the results suggest the involvement of mast cells in the induction of fibrosis and modulation of endothelial cell function in GCFs. PMID- 21035109 TI - Microarray and quantitative RT-PCR analyses in calcium-channel blockers induced gingival overgrowth tissues of periodontitis patients. AB - OBJECTIVES: The purpose of the present study was to analyse transcriptomes and mRNA expression levels for specific genes in calcium-channel blocker-induced gingival overgrowth (GO) tissues. DESIGN: Eight gingival tissues samples (from both GO negative and positive sites) were harvested from four GO patients for microarray analyses. Twelve candidate genes were selected for further quantitative real time reverse transcription-polymerase chain reaction (qRT-PCR) analyses. Ten GO tissues from periodontitis patients and ten control gingival tissues from healthy subjects were compared by qRT-PCR. Mann-Whitney U-test was used for statistical evaluation. RESULTS: In GO positive tissues, 163-1631 up regulated and 100-695 down-regulated genes were identified with more than two fold changes compared with GO negative tissues amongst patients by microarray experiments. No commonly expressed genes amongst the eight sets of microarray data were found. The clustering analysis confirmed that the entire transcriptome patterns showed similarities in individuals, but differences amongst the four patients. The qRT-PCR and statistical analyses for the candidate genes, though, revealed differential gene expressions between GO-positive and negative tissues. We found that matrix metalloproteinase (MMP)-1 and MMP-12 as well as cathepsin-L were significantly up-regulated whilst keratin-10 and transforming growth factor beta1 were significantly down-regulated in GO tissues of periodontitis patients compared with the control gingival tissues of healthy subjects. CONCLUSION: The microarray analyses revealed that GO pathogenesis was complex and individually varied, though GO-affected gingival tissues were controlled at least by genes related to collagen metabolisms including regulated MMPs, cathepsin-L, growth factors, and keratins to maintain tissue homeostasis in vivo. PMID- 21035110 TI - Investigation of the interleukin-1 gene cluster polymorphisms in Jordanian patients with chronic and aggressive periodontitis. AB - OBJECTIVE: Interleukin-1 (IL-1) is a proinflammatory cytokine that is highly elevated in response to bacterial biofilms and is a potential risk factor for periodontal diseases. IL-1 gene polymorphisms have been associated with the IL-1 level. The aim of this study was to investigate if IL-1 gene cluster polymorphisms are associated with chronic (CP) and aggressive (AgP) periodontitis in a Jordanian population. METHODS: A total of 100 CP, 80 AgP patients and 80 controls were genotyped using PCR for IL-1RN-86-bp VNTR and PCR-RFLP for IL-1A 889, IL-1B-511, -35, +3953, and IL-1RN +8006, +9589, +11100 SNPs. The distribution of alleles and genotypes between groups was compared using chi(2) analysis. Estimation of haplotype frequencies was carried out using the EH programme. RESULTS: The IL-1RN8006 SNP and the IL-1RN-VNTR were associated with CP but not with AgP. The C allele and TC genotype of IL-1RN8006 were increased in CP (P(corr)=0.002, 0.00026 respectively). The A1 allele and A1/A1 genotype of the IL1-RN-VNTR were significantly increased in CP (P(corr)=0.0007, <0.0001 respectively). The CA1 haplotype formed by both markers was present in 29 CP patients but not in any of the controls (P<0.0001). No significant differences were found in the distribution of allele and genotype frequencies of the other markers between CP and AgP cases and controls. CONCLUSIONS: IL-1RN 8006 and IL 1RN VNTR were associated with CP but not AgP in a Jordanian population, whilst other investigated markers in IL-1A, IL-1B and IL-1RN were not associated with either CP or AgP. PMID- 21035111 TI - Oestrogen inhibits osteoclast formation induced by periodontal ligament fibroblasts. AB - OBJECTIVE: Since tooth-associated fibroblasts are taken to participate in the formation of osteoclasts and it is unknown whether oestrogen affects this process, the effects of 17beta-estradiol (17beta-E(2)) were studied on osteoclastogenesis induced by human periodontal ligament fibroblasts (PLFs) and gingival fibroblasts (GFs). METHODS: Human peripheral blood mononuclear cells (PBMCs) were seeded on monolayers of PLFs and GFs and cocultured for 14 days in the presence or absence of various concentrations of 17beta-E(2). The number of tartrate resistant acid phosphatase (TRACP)-positive osteoclast-like cells (OCs) was assessed. In addition, we analysed the PBMC-induced withdrawal of the fibroblasts. mRNA expression was determined of oestrogen receptor (ER)-alpha, ER beta, receptor activator nuclear factor kappa B ligand (RANKL), and osteoprotegerin (OPG) by PLFs and GFs. RESULTS: PBMCs induced a higher number and larger fibroblast-free areas if cocultured with PLFs than with GFs. Concomitantly, the number of TRACP-positive OCs was significantly higher in PLF cocultures. 17beta-E(2) inhibited the formation of OCs in PLF cocultures. 17beta E(2) did not alter the expression of RANKL, OPG, and ER-alpha mRNAs in either fibroblast cell population. CONCLUSION: Our data indicate that PLFs may promote osteoclastogenesis more strongly than GFs. 17beta-E(2) inhibits the PLF-induced formation of osteoclast-like cells. Thus, the inhibitory effect of oestrogen on osteoclast formation appears to be cell type dependent. PMID- 21035112 TI - Self-assembly of 6-O- and 6'-O-hexadecylsucroses mixture under aqueous conditions. AB - In this paper, we report the self-assembly of 6-O- and 6'-O-hexadecylsucroses mixture under aqueous conditions. The mixture was synthesized by a five-step sequence from sucrose. The SEM image of a sample prepared by drying a dispersion of the mixture in water showed nanoparticles with the diameter of ~50nm and aggregates that were formed by further assembly of them. The XRD measurement of the sample exhibited the diffraction pattern assignable to face-centered cubic (FCC) structure and the diameter of a sphere, which took part in the FCC structure, was calculated to be 5.1nm. This value was relatively close to that observed in the DLS measurement of a dispersion of the mixture in water and estimated for a spherical micelle based on the molecular sizes of the two sucrose ethers. On the basis of the above findings, the following self-assembly process of the mixture under aqueous conditions was proposed. The mixture formed the spherical micelles with the diameter of ~5-7nm in water. The micelles regularly organized according to the FCC structure during the drying process from the aqueous dispersion to construct the nanoparticles with the diameter of ~50nm. Several numbers of the nanoparticles further assembled to form the aggregates. PMID- 21035113 TI - Understanding the statistical persistence of dual-axis swallowing accelerometry signals. AB - Swallowing accelerometry is a biomechanical approach for the assessment of difficulties during deglutition. However, the effects of various swallowing tasks and different anthropometric/demographic variables on the statistical behavior of these accelerometric signals are unknown. In particular, to understand the statistical persistence of these signals, we used detrended fluctuation analysis (DFA) to analyze accelerometric data collected from 408 healthy participants during dry, wet and wet chin tuck swallowing tasks. The results of DFA were then examined for potential influences of age, gender or body mass index. Several important conclusions were reached. First, the strongest persistence was observed for the wet chin tuck swallows. Second, the vibrations in the superior-inferior (S-I) direction generally have stronger temporal dependencies than those in the anterior-posterior (A-P) direction. Both of these phenomena can be attributed to the dominating influence of head movements on the amplitude of vibrations in the S-I direction. Third, gender, age and body mass index of the participants did not impact the observed persistence for dry and wet chin tuck swallows, while a gender effect was identified for wet swallows. In particular, male participants experienced more Brownian-like statistical dependencies in their swallowing signals. Future developments in the field should attempt to remove signal components associated with strong statistical persistence, as they tend to be associated with non-swallowing phenomena. PMID- 21035114 TI - Calculating summary statistics for population chemical biomonitoring in women of childbearing age with adjustment for age-specific natality. AB - The effects of chemical exposures during pregnancy on children's health have been an increasing focus of environmental health research in recent years, leading to greater interest in biomonitoring of chemicals in women of childbearing age in the general population. Measurements of mercury in blood from the National Health and Nutrition Examination Survey are frequently reported for "women of childbearing age," defined to be of ages 16-49 years. The intent is to represent prenatal chemical exposure, but blood mercury levels increase with age. Furthermore, women of different ages have different probabilities of giving birth. We evaluated options to address potential bias in biomonitoring summary statistics for women of childbearing age by accounting for age-specific probabilities of giving birth. We calculated median and 95th percentile levels of mercury, PCBs, and cotinine using these approaches: option 1: women aged 16-49 years without natality adjustment; option 2: women aged 16-39 years without natality adjustment; option 3: women aged 16-49 years, adjusted for natality by age; option 4: women aged 16-49 years, adjusted for natality by age and race/ethnicity. Among the three chemicals examined, the choice of option has the greatest impact on estimated levels of serum PCBs, which are strongly associated with age. Serum cotinine levels among Black non-Hispanic women of childbearing age are understated when age-specific natality is not considered. For characterizing in utero exposures, adjustment using age-specific natality provides a substantial improvement in estimation of biomonitoring summary statistics. PMID- 21035115 TI - [Prognosis of urinary tract infections with discordant antibiotic treatment]. AB - INTRODUCTION: This study aims to evaluate the prognosis of urinary tract infections (UTI) treated empirically with inadequate antibiotic treatment. MATERIAL AND METHODS: Prospective cohort study of patients over 18 years of age, attended in the hospital emergency service between 01/02 and 31/05 of 2007, due to micturation symptoms, accompanied by pyuria (>10 leukocytes/mm(3) of uncentrifuged urine) or positive reactive strip for nitrites-leukocytes and urine culture with >10(3) colony forming units. It was considered that the antibiotic treatment prescribed empirically was adequate if the bacteria isolated was sensitive and had been prescribed for the correct time. It was considered that there was therapeutic failure when the symptoms persisted after 5 days of treatment. Age, gender, presence of indwelling bladder catheter, type of UTI, hospitalization in the previous 3 months, origin of the patient and associated diseases were recorded. RESULTS: A total of 177 bacteria were isolated in 168 patients. In 29 cases (17.3%), the microorganism isolated was resistant to the antibiotic prescribed. There was thereaputic failure in only 6 patients, although they did not required hospital admission. The patients who lived in a residential home for the elderly (13.7% vs 2.2%, P = 0.015) or who had been hospitalized during the previous 3 months (20.6% vs 4.3%, p = 0.039) had a greater risk of receiving inadequate treatment. CONCLUSIONS: The prognosis of the patients attended in the emergency hospital service due to UTI with discordant antibiotic treatment is favorable in most of the cases. Performing urine culture in patients with greater risk of suffering UTI due to a resistant microorganism would be recommendable. PMID- 21035116 TI - Urine bisphenol-A (BPA) level in relation to semen quality. AB - OBJECTIVE: To determine whether urine bisphenol-A (BPA) levels are associated with lower semen quality. DESIGN: Cohort study. SETTING: Four regions in China where high exposure to BPA in the workplace existed. PATIENT(S): 218 men with and without BPA exposure in the workplace. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Semen parameters. RESULT(S): After adjustment for potential confounders using linear regression, increasing urine BPA level was statistically significantly associated with [1] decreased sperm concentration, [2] decreased total sperm count, [3] decreased sperm vitality, and [4] decreased sperm motility. Compared with men who did not have detectable urine BPA levels, those with detectable urine BPA had more than three times the risk of lowered sperm concentration and lower sperm vitality, more than four times the risk of lower sperm count, and more than twice the risk of lower sperm motility. The urine BPA level was not associated with semen volume or abnormal sperm morphology. Similar dose-response associations were observed among men with environmental BPA exposure at levels comparable with those in the U.S population. Despite a markedly reduced sample size, the inverse correlation between increased urine BPA levels and decreased sperm concentration and total sperm count remained statistically significant. CONCLUSION(S): These results provide the first epidemiologic evidence of an adverse effect of BPA on semen quality. PMID- 21035117 TI - Cremation practices coexisting at the S'Illot des Porros Necropolis during the Second Iron Age in the Balearic Islands (Spain). AB - The necropolis of S'Illot des Porros, one of the most important prehistoric funerary sites of the Balearic Islands (Spain), was in use from the VIth and Vth century BCE until the Ist century CE. Located in a funerary area which contains two cementeries and one sanctuary, this site is constituted by three funerary chambers named A, B and C, respectively. Investigations on all the human burnt bone remains of the chambers, carried out mainly by the X-ray diffraction and supplemented in some cases by Fourier Transform Infrared spectroscopy pointed to the simultaneous use of inhumation and cremation funerary rites, probably due to existing social differences. In particular, it was argued that the chambers were differentiated, i.e., B was dedicated to inhumations and A to cremations, the cremations found in chamber B very likely being a result of a cleaning purification of the burial area. Moreover, chamber C, which is the most ancient (IVth century BCE) and with the largest number of inhumed remains, contains the smallest number of remains that were exposed to fire and just in one case it seems possible to attribute a genuine high-temperature cremation. PMID- 21035118 TI - Pre-hospital haemostatic dressings: a systematic review. AB - BACKGROUND: Uncontrolled haemorrhage is a leading cause of prehospital death after military and civilian trauma. Exsanguination from extremity wounds causes over half of preven military combat deaths and wounds to the anatomical junctional zones provide a particular challenge for first responders. Commercial products have been developed, which claim to outperform standard gauze bandages in establishing and maintaining non-surgical haemostasis. Since 2004, two advanced haemostatic dressing products, HemCon and QuikClot have been widely deployed in military operations. Newer products have since become available which aim to provide more efficient haemostasis than and thus supersede HemCon and QuikClot. AIM: To conduct a systematic review of clinical and preclinical evidence to compare the relative efficacy and safety of available haemostatic products, which are of relevance to pre-hospital military and civilian emergency medical providers. METHOD: An English language literature search was performed, using PubMed and Web of Knowledge Databases, with cross-referencing, focussed product searches and communication with product manufacturers. For studies employing animal models, the injury model was required to produce fatal haemorrhage. Products were categorised by primary mode of action as either factor concentrators,mucoadhesive agents or procoagulant supplementors. RESULTS: From 60 articles collated, 6 clinical papers and 37 preclinical animal trials were eligible for inclusion in this review. Products have been tested in three different types of haemorrhage model: low pressure, high volume venous bleeding, high pressure arterial bleeding and mixed arterial-venous bleeding. The efficacy of products varies with the model adopted. Criteria for the 'ideal battle field haemostatic dressing' have previously been defined by Pusateri, but no product has yet attained suchstatus. Since 2004, HemCon (a mucoadhesive agent) and QuikClot (a factor concentrator) have been widely deployed by United States and United Kingdom Armed Forces; retrospective clinical data supports their efficacy. However, in some recent animal models of lethal haemorrhage, WoundStat(mucoadhesive), Celox (mucoadhesive) and CombatGauze (procoagulant supplementor) have all outperformed both HemCon and QuikClot products. CONCLUSION: HemCon and QuikClot have augmented the haemostatic capabilities of the military first aid responder, but newer products demonstrate potential to be more effective and should be considered as replacements for current in service systems. These products could have utility for civilian pre-hospital care. PMID- 21035119 TI - Raman and mechanical properties correlate at whole bone- and tissue-levels in a genetic mouse model. AB - The fracture resistance of bone arises from the composition, orientation, and distribution of the primary constituents at each hierarchical level of organization. Therefore, to establish the relevance of Raman spectroscopy (RS) in identifying differences between strong or tough bone and weak or brittle bone, we investigated whether Raman-derived properties could explain the variance in biomechanical properties at both the whole bone and the tissue-level, and do so independently of traditional measurements of mineralization. We harvested femurs from wild-type mice and mice lacking matrix metalloproteinase 2 because the mutant mice have a known reduction in mineralization. Next, RS quantified compositional properties directly from the intact diaphysis followed by micro computed tomography to quantify mineralization density (Ct.TMD). Correlations were then tested for significance between these properties and the biomechanical properties as determined by the three-point bending test on the same femurs. Harvested tibia were embedded in plastic, sectioned transversely, and polished in order to acquire average Raman properties per specimen that were then correlated with average nanoindentation properties per specimen. Dividing the nu(1) phosphate by the proline peak intensity provided the strongest correlation between the mineral-to-collagen ratio and the biomechanical properties (whole bone modulus, strength, and post-yield deflection plus nanoindentation modulus). Moreover, the linear combination of nu(1) phosphate/proline and Ct.TMD provided the best explanation of the variance in strength between the genotypes, and it alone was the best explanatory variable for brittleness. Causal relationships between Raman and fracture resistance need to be investigated, but Raman has the potential to assess fracture risk. PMID- 21035120 TI - Pressure distribution over the palm region during forward falls on the outstretched hands. AB - Falls on the outstretched hands are the cause of over 90% of wrist fractures, yet little is known about bone loading during this event. We tested how the magnitude and distribution of pressure over the palm region during a forward fall is affected by foam padding (simulating a glove) and arm configuration, and by the faller's body mass index (BMI) and thickness of soft tissues over the palm region. Thirteen young women with high (n=7) or low (n=6) BMI participated in a "torso release experiment" that simulated falling on both outstretched hands with the arm inclined either at 20 degrees or 40 degrees from the vertical. Trials were acquired with and without a 5 mm thick foam pad secured to the palm. Outcome variables were the magnitude and location of peak pressure (d, theta) with respect to the scaphoid, total impact force, and integrated force applied to three concentric areas, including "danger zone" of 2.5 cm radius centered at the scaphoid. Soft tissue thickness over the palm was measured by ultrasound. The 5mm foam pad reduced peak pressure, and peak force to the danger zone, by 83% and 13%, respectively. Peak pressure was 77% higher in high BMI when compared with low BMI participants. Soft tissue thickness over the palm correlated positively with distance (d) (R=0.79, p=0.001) and force applied outside the danger zone (R=0.76, p=0.002), but did not correlate with BMI (R=0.43, p=0.14). The location of peak pressure was shunted 4 mm further from the scaphoid at 20 degrees than that of 40 degrees falls (d=25 mm (SD 8), theta=-9 degrees (SD 17) in the 20 degrees falls versus d=21 mm (SD 8), theta=-5 degrees (SD 24) in the 40 degrees falls). Peak force to the entire palm was 11% greater in 20 degrees compared with 40 degrees falls. These results indicate that even a 5 mm thick foam layer protects against wrist injury, by attenuating peak pressure over the palm during forward falls. Increased soft tissue thickness shunts force away from the scaphoid. However, soft tissue thickness is not predicted by BMI, and peak pressures are greater in high individuals than that of low BMI individuals. These results contribute to our understanding of the mechanics and prevention of wrist and hand injuries during falls. PMID- 21035121 TI - Determination of preservatives by integrative coupling method of headspace liquid phase microextraction and capillary zone electrophoresis. AB - An integrative coupling method of headspace liquid-phase microextraction (HS LPME) and capillary zone electrophoresis (CZE) was proposed in this paper. In the method, a separation capillary was used to create a microextraction droplet of the running buffer solution of CZE, hold the droplet at the capillary inlet, extract analytes of sample solutions in the headspace of a sample vial, inject concentrated analytes into the capillary and separate the analytes by CZE. The proposed method was applied to determine the preservatives of benzoic acid and sorbic acid in soy sauce and soft drink samples, in which the running buffer solution of 50 mmol/L tetraborate (pH 9.2) was directly used to form the acceptor droplet at the capillary inlet by pressure, and the preservatives in a 6-mL sample solution containing 0.25 g/mL NaCl were extracted at 90 degrees C for 30 min in the headspace of a 14-mL sample vial. Then the concentrated preservatives were injected into the capillary at 10 cm height difference for 20 s and separated by CZE. The enrichment factors of benzoic acid and sorbic acid achieved 266 and 404, and the limits of detection (LODs) were 0.03 and 0.01 MUg/mL (S/N=3), respectively. The recoveries were in the range of 88.7-105%. The integrative coupling method of HS-LPME and CZE was simple, convenient, reliable and suitable for concentrating volatile and semi-volatile organic acids and eliminating matrix interferences of real samples. PMID- 21035122 TI - Two-step stacking in capillary zone electrophoresis featuring sweeping and micelle to solvent stacking: I. Organic cations. AB - Two-step stacking of organic cations by sweeping and micelle to solvent stacking (MSS) in capillary zone electrophoresis (CZE) is presented. The simple procedure involves hydrodynamic injection of a micellar sodium dodecyl sulfate solution before the sample that is prepared without the micelles. The micelles sweep and transport the cations to the boundary zone between the sample and CZE buffer. The presence of organic solvent in the CZE buffer induces the second stacking step of MSS. The LODs obtained for the four beta blocker and two tricyclic antidepressant test drugs were 20-50 times better compared to typical injection. PMID- 21035123 TI - Selective extraction of melamine using 11-mercaptoundecanoic acid-capped gold nanoparticles followed by capillary electrophoresis. AB - This study describes the use of 11-mercaptoundecanoic acid-capped gold nanoparticles (MUA-AuNPs) for selective extraction of melamine prior to analysis by capillary electrophoresis with UV detection. The highest degree of melamine induced aggregation of MUA-AuNPs was found to occur at pH 5.0, indicating that the NP aggregation is mainly because of hydrogen bonding between the carboxylate groups of MUA and the amine groups of melamine. Moreover, the degree of melamine induced NP aggregation gradually increased when the chain length of the mercaptoalkanoic acid was increased from two to 12 carbon atoms. At pH 5.0, the extraction efficiency of melamine was highly dependent on the concentration of MUA-AuNPs, the concentration of dithiothreitol (DTT), the extraction time between MUA-AuNPs and melamine, and the incubation time between melamine-adsorbed AuNPs and DTT. The separation of the extracted melamine and DTT (releasing agent) was accomplished using a solution of 10 mM phosphate (pH 6.0) containing 1.6% (v/v) poly(diallyldimethylammonium chloride). Under the optimum extraction and separation conditions, the limit of detection at a signal-to-noise ratio of 3 was estimated to be 77 pM for melamine, with linear range of 1-1000 nM. The proposed method was successfully applied to the determination of melamine in tap water and in milk. PMID- 21035124 TI - Identification and quantification of phosphatidylcholines containing very-long chain polyunsaturated fatty acid in bovine and human retina using liquid chromatography/tandem mass spectrometry. AB - The retina is one of the vertebrate tissues with the highest content in polyunsaturated fatty acids (PUFA). A large proportion of retinal phospholipids, especially those found in photoreceptor membranes, are dipolyunsaturated molecular species. Among them, dipolyunsaturated phosphatidylcholine (PC) molecular species are known to contain very-long-chain polyunsaturated fatty acids (VLC-PUFA) from the n-3 and n-6 series having 24-36 carbon atoms (C24-C36) and four to six double bonds. Recent interest in the role played by VLC-PUFA arose from the findings that a protein called elongation of very-long-chain fatty acids 4 (ELOVL4) is involved in their biosynthesis and that mutations in the ELOVL4 gene are associated with Stargardt-like macular dystrophy (STD3), a dominantly inherited juvenile macular degeneration leading to vision loss. The aim of the present study was to develop an HPLC-ESI-MS/MS method for the structural characterisation and the quantification of dipolyunsaturated PC molecular species containing VLC-PUFA and validate this methodology on retinas from bovines and human donors. Successful separation of phosphatidylethanolamine (PE), phosphatidylinositol (PI), phosphatidylserine (PS), PC, lyso phosphatidylcholine (LPC) and sphingomyelin (SM) was achieved using a silica gel column and a gradient of hexane/isopropanol/water containing ammonium formate as a mobile phase. A complete structural characterisation of intact phosphatidylcholine species was obtained by collision-induced dissociation (CID) in the negative mode. Fatty acid composition and distribution can be clearly assigned based on the intensity of sn-2/sn-1 fragment ions. The PC species were characterised on bovine retina, 28 of which were dipolyunsaturated PC species containing one VLC-PUFA (C24-C36) with three to six double bonds. VLC-PUFA was always in the sn-1 position while PUFA at the sn-2 position was exclusively docosahexaenoic acid (DHA, C22:6n-3). Most of these VLC-PUFA-containing dipolyunsaturated PCs were detected and quantified in human retinas. The quantitative analysis of the different PC molecular species was performed in the positive mode using precursor ion scanning of m/z 184 and 14:0/14:0-PC and 24:0/24:0-PC as internal standards. The relationship between the MS peak intensities of different PC species and their carbon chain length was included for calibration. The main compounds represented were those having VLC-PUFA with 32 carbon atoms (C32:3, C32:4, C32:5 and C32:6) and 34 carbon atoms (C34:3, C34:4, C34:5 and C34:6). Dipolyunsaturated PCs with 36:5 and 36:6 were detected but in smaller quantities. In conclusion, this new HPLC-ESI-MS/MS method is sensitive and specific enough to structurally characterise and quantify all molecular PC species, including those esterified with VLC-PUFA. This technique is valuable for a precise characterisation of PC molecular species containing VLC PUFA in retina and may be useful for a better understanding of the pathogenesis of STD3. PMID- 21035125 TI - The co-emergence of cognition, language, and speech motor control in early development: a longitudinal correlation study. AB - Although the development of spoken language is dependent on the emergence of cognitive, language, and speech motor skills, knowledge about how these domains interact during the early stages of communication development is currently limited. This exploratory investigation examines the strength of associations between longitudinal changes in articulatory kinematics and development of skills in multiple domains thought to support early communication development. Twenty four children were investigated every 3 months between the ages of 9 and 21 months. Movements of the upper lip, lower lip, and jaw were transduced using a three-dimensional motion capture system to obtain age-related changes in movement speed and range of movement. Standardized measures of cognition and language from the Battelle Developmental Inventory, 2nd edition and the MacArthur-Bates Communicative Development Inventory were also collected. Significant associations were identified between orofacial kinematic and the standardized measures of language and cognitive skills, even when age served as covariate. These findings provide preliminary evidence of interactions between cognition, language, and speech motor skills during early communication development. Further work is needed to identify and quantify causal relations among these co-emerging skills. LEARNING OUTCOMES: The reader will be able to: (1) describe how cognition, language, and speech motor control may interact during speech development, (2) describe the associations between speech kinematic characteristics and measures of cognition and language. PMID- 21035126 TI - Whorf reloaded: language effects on nonverbal number processing in first grade--a trilingual study. AB - The unit-decade compatibility effect is interpreted to reflect processes of place value integration in two-digit number magnitude comparisons. The current study aimed at elucidating the influence of language properties on the compatibility effect of Arabic two-digit numbers in Austrian, Italian, and Czech first graders. The number word systems of the three countries differ with respect to their correspondence between name and place value systems; the German language is characterized by its inversion of the order of tens and units in number words as compared with digital notations, whereas Italian number words are generally not inverted and there are both forms for Czech number words. Interestingly, the German-speaking children showed the most pronounced compatibility effect with respect to both accuracy and speed. We interpret our results as evidence for a detrimental influence of an intransparent number word system place value processing. The data corroborate a weak Whorfian hypothesis in children, with even nonverbal Arabic number processing seeming to be influenced by linguistic properties in children. PMID- 21035127 TI - The developing role of prosody in novel word interpretation. AB - This study examined whether children use prosodic correlates to word meaning when interpreting novel words. For example, do children infer that a word spoken in a deep, slow, loud voice refers to something larger than a word spoken in a high, fast, quiet voice? Participants were 4- and 5-year-olds who viewed picture pairs that varied along a single dimension (e.g., big vs. small flower) and heard a recorded voice asking them, for example, "Can you get the blicket one?" spoken with either meaningful or neutral prosody. The 4-year-olds failed to map prosodic cues to their corresponding meaning, whereas the 5-year-olds succeeded (Experiment 1). However, 4-year-olds successfully mapped prosodic cues to word meaning following a training phase that reinforced children's attention to prosodic information (Experiment 2). These studies constitute the first empirical demonstration that young children are able to use prosody-to-meaning correlates as a cue to novel word interpretation. PMID- 21035128 TI - Detection of gastroesophageal reflux in children using combined multichannel intraluminal impedance and pH measurement: data from the German Pediatric Impedance Group. AB - OBJECTIVE: To validate the use of combined multichannel intraluminal impedance (MII)-pH (MII-pH) monitoring for detecting gastroesophageal reflux (GER) in children in daily clinical practice. STUDY DESIGN: The patients were divided into 3 symptom groups based on the main indication for the procedure. MII-pH monitoring was performed in 700 children presenting with symptoms suggestive of GER, including 329 children with pulmonary symptoms, 325 with gastrointestinal symptoms, and 46 with neurologic symptoms. The MII-pH results were compared with pH monitoring alone, and retrograde bolus movements, symptom index, and symptom association probability were compared. RESULTS: Overall, 270 measurements were abnormal: 101 (37%) showed abnormal MII-pH study, 49 (18%) showed only pathological pH measurements and 120 measurements (45%) had an abnormal MII recording only. Extraintestinal symptoms of GER were seen more often in younger children and were more often related to a normal pH study but an abnormal MII study. Infants had a significantly higher number of retrograde bolus movements than older children. Symptom index and symptom association probability showed moderate agreement (Cohen kappa, 0.54). CONCLUSIONS: From this large systematically standardized data collection of MII-pH measurements in children, we conclude that 45% of the patients with abnormal GER would not have been recognized by 24-hour pH measurement alone. Our findings confirm that MII-pH is superior to pH monitoring alone in detecting GER. PMID- 21035129 TI - Pediatric non-high-density lipoprotein cholesterol, the metabolic syndrome, and insulin resistance. PMID- 21035130 TI - The role and interpretation of pilot studies in clinical research. AB - Pilot studies represent a fundamental phase of the research process. The purpose of conducting a pilot study is to examine the feasibility of an approach that is intended to be used in a larger scale study. The roles and limitations of pilot studies are described here using a clinical trial as an example. A pilot study can be used to evaluate the feasibility of recruitment, randomization, retention, assessment procedures, new methods, and implementation of the novel intervention. A pilot study is not a hypothesis testing study. Safety, efficacy and effectiveness are not evaluated in a pilot. Contrary to tradition, a pilot study does not provide a meaningful effect size estimate for planning subsequent studies due to the imprecision inherent in data from small samples. Feasibility results do not necessarily generalize beyond the inclusion and exclusion criteria of the pilot design. A pilot study is a requisite initial step in exploring a novel intervention or an innovative application of an intervention. Pilot results can inform feasibility and identify modifications needed in the design of a larger, ensuing hypothesis testing study. Investigators should be forthright in stating these objectives of a pilot study. Grant reviewers and other stakeholders should expect no more. PMID- 21035131 TI - The effects of barrier materials on reduction of pericardial adhesion formation in rabbits: a comparative study of a hyaluronan-based solution and a temperature sensitive poloxamer solution/gel material. AB - OBJECTIVE: This study was performed to examine the efficacy and safety of a hyaluronan solution (Guardix-SL) and a temperature sensitive poloxamer solution/gel material (Guardix-SG) on the prevention of pericardial adhesion in rabbits. METHODS: A total of 60 rabbits were divided into three groups according to material applied after epicardial abrasion: the control group (group CO), the Guardix SL group (group SL), and the Guardix SG group (group SG). The ejection fraction and the presence of pericardial effusion were evaluated by echocardiograms at the immediate postoperative period and 2 wk after the surgery. The adhesion was evaluated macroscopically and microscopically 2 wk after the surgery. RESULTS: In the group SG, mild pericardial effusions were observed only at the immediate postoperative period in 10 out of 20 rabbits with an insignificant reduction of the ejection fraction. Group CO had a significantly higher macroscopic adhesion and fibrosis score than did groups SL and SG (P < 0.001), and group SL had a significantly higher adhesion score than did group SG (P = 0.045). Inflammation score and the expression of anti-macrophage antibody in group CO were higher than those in groups SL and SG, although the differences were not significant. CONCLUSIONS: Guardix-SL and Guardix-SG effectively reduced the adhesion formation, and Guardix-SG is more effective than Guardix-SL for preventing adhesion. However, Guardix-SG showed a potential disadvantage of decreasing the ejection fraction, although this was statistically insignificant. Further study to verify the appropriate dosage to maximize the therapeutic effect without decreasing the heart function is needed. PMID- 21035132 TI - Tramadol use for axillary brachial plexus blockade. AB - BACKGROUND: We investigated the effects of tramadol added to the mixture of local anesthetic for axillary brachial plexus blockade (ABB) in patients to have undergone hand and forearm surgery. MATERIALS AND METHODS: Forty patients from the ASA classification I and II, between 18 and 60 y of age, were included in this randomized double-blind study. Group C: levobupivacaine (150 mg) + lidocaine (200 mg) (n = 20), Group T: levobupivacaine (150 mg), + lidocaine (200 mg) + tramadol (100 mg) (n = 20). Intravenous midazolam of 0.02 mg/kg was given for premedication. ABB was performed with 42 mL mixture of local anesthetic, using peripheral nerve stimulator. The duration of onset of motor and sensory blockades was recorded. The postoperative first analgesic need, sedation, and satisfaction score and side effects were recorded. RESULTS: There was no significant difference between the groups regarding intraoperative visual analog scale (VAS), hemodynamics, adverse effects, sedative and analgesic requirement, and the patient satisfaction. The development of motor block at the median nerve on the 5th min (P = 0.03) and at the ulnar nerve on 10th and 15th min in Group T were (P = 0.01, P = 0.03, respectively) considerably longer than that in Group C. CONCLUSIONS: Adding 100 mg of tramadol to the combination of levobupivacaine and lidocaine during ABB could not provide an important clinical effect in patients undergoing hand and forearm surgery. PMID- 21035133 TI - Ischemic preconditioning decreases mitochondrial proton leak and reactive oxygen species production in the postischemic heart. AB - BACKGROUND: Proton leak (H(+) leak) dissipates mitochondrial membrane potential (mDeltaPsi) through the re-entry of protons into the mitochondrial matrix independent of ATP synthase. Changes in H(+) leak may affect reactive oxygen species (ROS) production. We measured H(+) leak and ROS production during ischemia-reperfusion and ischemic preconditioning (IPC) and examined how changing mitochondrial respiration affected mDeltaPsi and ROS production. MATERIALS AND METHODS: Isolated rat hearts (n = 6/group) were subjected to either control-IR or IPC. Rate pressure product (RPP) was measured. Mitochondria were isolated at end reperfusion. Respiration was measured by polarography and titrated with increasing concentrations of malonate (0.5-2 mM). mDeltaPsi was measured using a tetraphenylphosphonium electrode. H(+) leak is the respiratory rate required to maintain membrane potential at -150 mV in the presence of oligomycin-A. Mitochondrial complex III ROS production was measured by fluorometry using Amplex red. RESULTS: IPC improved recovery of RPP at end reperfusion (63% +/- 4% versus 21% +/- 2% in control-IR, P < 0.05). Ischemia-reperfusion caused increased H(+) leak (94 +/- 12 versus 31 +/- 1 nmol O/mg protein/min in non-ischemic control, P < 0.05). IPC attenuates these increases (55 +/- 9 nmol O/mg protein/min, P < 0.05 versus control-IR). IPC reduced mitochondrial ROS production compared with control-IR (31 +/- 2 versus 40 +/- 3 nmol/mg protein/min, P < 0.05). As mitochondrial respiration decreased, mDeltaPsi and mitochondrial ROS production also decreased. ROS production remained lower in IPC than in control-IR for all mDeltaPsi and respiration rates. CONCLUSIONS: Increasing H(+) leak is not associated with decreased ROS production. IPC decreases both the magnitude of H(+) leak and ROS production after ischemia-reperfusion. PMID- 21035134 TI - MRI quantitative study and pathologic analysis of crush injury in rabbit hind limb muscles. AB - BACKGROUND: To explore the value of quantitative magnetic resonance imaging (i.e., T2 map technique) in the diagnosis of crush injury in rabbit hind limb muscles. MATERIALS AND METHODS: We established a rabbit hind limb crush injury model and performed examinations on magnetic resonance imaging (MRI) (T1WI, T2WI, and T2 map), muscle pathology, serum level of muscular troponin (sTnI), and urine myoglobin (Myo) at 1, 3, 7, 14, and 30 d after injury to investigate the correlation of MRI, library examination, and histopathology. RESULTS: T2WI of the injured muscle showed high signal intensity at 1, 3, and 7 d after crush injury and the T2 value continued to rise. The pathologic findings of the muscle included swollen and ruptured cells, expanded extra-cellular space, inflammatory reactions, and fine muscle fiber regeneration. The serum sTnI and urine Myo were high. At 14 d, these indices returned to normal gradually. The T2WI changes and T2 value were positively associated with the pathological changes of the muscles, serum sTnI and urine Myo. However, the signal intensity of T1WI did not vary significantly at different time points. CONCLUSION: T2WI and T2 value from T2 mapping are very useful methods of choice to evaluate the distribution and extension of the affected muscles. The high signal intensity on T2WI of the affected muscles after crush injury may be due to an increased extracellular space, local inflammation, and incomplete muscle fiber regeneration. PMID- 21035135 TI - Bioactivities of sophorolipid with different structures against human esophageal cancer cells. AB - BACKGROUND: Sophorolipids (SLs) obtained from yeast broth are mixtures of many sophorolipid molecules with different structures, and have attracted more attention since they were found to have good antimicrobial, anticancer, anti inflammatory, and anti-HIV activities. We investigated the effects of sophorolipid molecules with different structures on human esophageal cancer cells in the present work. MATERIALS AND METHODS: Ten sophorolipid (SL) molecules were separated and purified from the sophorolipids mixture using preparative HPLC, and their structures were identified by MS analyses. The effects of sophorolipid molecules with different structures on two human esophageal cancer cell lines, KYSE 109 and KYSE 450, were investigated by MTT assay. RESULTS: The structures of the 10 sophorolipid molecules differ in acetylation degree of sophorose, unsaturation degree of hydroxyl fatty acid, and lactonization or ring opening. The results demonstrated that the inhibition of diacetylated lactonic sophorolipid on two esophageal cancer cells (total inhibition at 30 MUg/mL concentration) was stronger than that of monoacetylated lactonic sophorolipid (totally inhibition at 60 MUg/mL concentration). Difference of unsaturation degree of hydroxyl fatty acid in SL molecules also had obvious influence on their cytotoxicity to esophageal cancer cells. The sophorolipid with one double bond in fatty acid part had the strongest cytotoxic effect on two esophageal cancer cells (total inhibition at 30 MUg/mL concentration). Acidic sophorolipid showed hardly any anticancer activity against esophageal cancer cells. CONCLUSIONS: In this study, the relationship of anticancer activities of natural sophorolipid molecules and the differences in their structures was revealed, which probably further reveals the mechanism of SL bioactivities and will be helpful in the modification of SL structures to obtain more novel SLs with excellent bioactivities. PMID- 21035136 TI - Lymphatic patterns of colorectal liver metastases. AB - BACKGROUND: Hematogenous spread is considered the predominant pathway for development of colorectal liver metastases (CRLM) and subsequent further tumor dissemination portal nodal involvement is also frequently observed in such cases, suggesting that lymphatics may have a role in the spread of CRLM. The role of lymphatics in the development of liver metastases is, however, controversial. The lymphatic patterns of CRLM were determined using a well established murine model. METHODS: CRLM were induced using a well established murine intrasplenic colorectal cancer model. Tumors were assessed at varying stages of development, and lymphatic patterns were determined in tumors and liver by immunohistochemistry staining for podoplanin and LYVE-1. Blood vessels were characterized using the vascular marker CD-34. Assessment was undertaken using digital microscopy and image analysis. RESULTS: Peri- and intratumoral lymphatic vessels were identified by podoplanin staining in all metastases and significantly increased with tumor growth. LYVE-1 staining was also noted but was variable. There was a concurrent significant increase in portal lymphatic staining within the normal liver with increasing growth of CRLM. CONCLUSION: There is increased expression of lymphatics within CRLM and normal liver with increasing tumor growth. Lymphatic development is likely to play a significant role in the intrahepatic and periportal dissemination of CRLM. PMID- 21035137 TI - Lateral position with the remaining lung uppermost improves matching of pulmonary ventilation and perfusion in pneumonectomized pigs. AB - BACKGROUND: Pneumonectomy is a major surgery. Severe hypoxemia sometimes occurs after pneumonectomy. Effective gas exchange depends on perfect pulmonary ventilation (V(A)) and perfusion (Q) matching. The effect of position on V(A)/Q matching after pneumonectomy is not clear. We therefore conducted this study to examine the effects of supine, left lateral decubitus (LLD), and right lateral decubitus (RLD) positions on V(A)/Q matching and gas exchange after pneumonectomy in a porcine model. METHODS: Twelve pigs were anesthetized and mechanically ventilated; six pigs received right pneumonectomy and six pigs received left pneumonectomy. The positions of the pigs were changed to supine, LLD, and RLD in random order after pneumonectomy. We applied intravenous and aerosolized high resolution fluorescent microsphere technique (FMT) to mark V(A) and Q in conjunction with arterial blood gas analysis to study these variables at different positions. Mechanical ventilation was kept constant throughout. RESULTS: Different positions after pneumonectomy lead to significant changes in heterogeneity and matching of V(A)/Q. In right pneumonectomized pigs, the highest PaO(2), lowest V(A)/Qheterogeneity, and highest matching of V(A)/Q was in RLD. In left pneumonectomized pigs, the highest PaO(2), lowest V(A)/Q heterogeneity, and highest matching of V(A)/Q was in LLD. CONCLUSIONS: The lateral position with the remaining lung uppermost leads to the highest V(A)/Q matching and best gas exchange after pneumonectomy. PMID- 21035138 TI - Vagus nerve preservation selectively restores visceral fat volume in patients with early gastric cancer who underwent gastrectomy. AB - BACKGROUND: Body weight loss is a well-known complication after gastrectomy, and is mainly due to reduced fat volume. The effect of vagotomy on the postoperative fat volume was investigated in patients with early stage gastric cancer who underwent gastrectomy. METHODS: Subcutaneous fat area (SFA) and visceral fat area (VFA) were separately measured in a computed tomographic (CT) image at the level of the umbilicus using Fat Scan software. The changes in these two fat areas were determined by comparing CT images taken before and more than 6 mo after gastrectomy, and the ratio of postoperative to preoperative fat area was calculated in 77 patients. RESULTS: VFA was reduced significantly greater after total gastrectomy (TG) than distal gastrectomy (DG) (P = 0.0003). In 63 patients who underwent DG, the reduction in VFA, but not in SFA, was significantly less in vagus nerve-preserved than in vagus nerve-nonpreserved cases (59.0% +/- 24.2% versus 74.9% +/- 28.2%, P = 0.027). If compared in each case, VFA showed a significantly greater decrease than did SFA in vagus-nonpreserving, but not in vagus-preserving, gastrectomy (68.2% +/- 37.0% versus 52.7% +/- 25.2%, P < 0.0001; 76.3% +/- 30.0% versus 74.9% +/- 28.2%, P = 0.79). CONCLUSIONS: The vagus nerve has a function to locally regulate the amount of intra-abdominal fat tissue, and selective vagotomy in gastrectomy results in a preferential reduction of visceral fat in gastrectomy. Surgical denervation of vagus may be reconsidered as a reasonable treatment for excessive obesity. PMID- 21035139 TI - NKT cells: the culprits of sepsis? AB - Sepsis is currently a leading cause of death in hospital intensive care units. Previous studies suggest that the pathophysiology of sepsis involves the hyperactivation of complex pro-inflammatory cascades that include the activation of various immune cells and the exuberant secretion of pro-inflammatory cytokines by these cells. Natural killer T-cells (NKT) are a sub-lineage of T cells that share characteristics of conventional T cells and NK cells, and bridge innate and adaptive immunity. More recently, NKT cells have been implicated in microbial immunity, including the onset of sepsis. Moreover, apolipoprotein E (apoE), a component of triglyceride-rich lipoproteins, has been shown to be protective in endotoxemia and gram-negative infections in addition to its well-known role in lipid metabolism. Here, we will review the role of NKT cells in sepsis and septic shock, the immunoregulatory role of apoE in the host immune response to infection, and propose a mechanism for this immunoregulation. PMID- 21035140 TI - The effects of dexamethasone, ascorbic acid, and beta-glycerophosphate on osteoblastic differentiation by regulating estrogen receptor and osteopontin expression. AB - BACKGROUND: Ascorbic acid (AA), beta-glycerophosphate (GP), and dexamethasone (DEX) are the compounds known to favor the expression of the osteoblastic phenotype in several bone cell systems. MATERIALS AND METHODS: In this report, the combination effects of differentiation agents on osteoprecursor cells were evaluated. The effect on cell proliferation was determined by a cell viability test with morphologic analysis. Differentiation and mineralization were evaluated using an alkaline phosphatase activity test and alizarin red-S staining. Protein expressions related to bone formation, such as transforming growth factor-beta (TGF-beta), estrogen receptor-alpha (ER-alpha), and osteopontin (OPN) were evaluated by using a Western blot analysis. RESULTS AND CONCLUSION: AA and GP provided an inductive effect for differentiation of osteoprecusor cells, while short-term application of DEX seemed to lead to a dose-dependent increase of cellular differentiation. Long-term use of DEX seemed to reduce mineralization. These effects may seem to be regulated by the expression of ER-alpha, OPN, and TGF-beta. Further studies related to this mechanism within the in vivo model may be necessary to ascertain greater detail. PMID- 21035141 TI - Aetiologies of altered states of consciousness: a prospective hospital-based study in a series of 464 patients of northern Tanzania. AB - BACKGROUND: Empirical knowledge suggests that altered states of consciousness are common in sub-Saharan Africa. However, to date prevalence studies are scarce. METHODS: The study was conducted at the Haydom Lutheran Hospital in northern Tanzania. Over a period of eight months all patients with altered states of consciousness were seen prospectively by a neurologist. The study population was subdivided into patients with acute confusional states (ACS) and those with impairment of consciousness (IOC). RESULTS: Out of 768 patients with neurological/psychiatric diagnoses 464 patients (60.4%) with altered states of consciousness were admitted. 159 patients had ACS (20.7%) and 447 IOC (58.2%). The diagnoses were not mutually exclusive. The most frequent aetiologies were of non-infectious origin. In patients with ACS, non-infectious encephalopathy, psychiatric disorder and dementia made up for 13.8%, 7.6% and 6.9%, respectively. In 25.2% of the cases with ACS, the reason remained obscure. In patients with IOC, the leading causes were epileptic seizures (febrile seizures 20.6% and epilepsy 13.9%) and head trauma 13.9%. Both ACS and IOC carried a bleak prognosis with 26% and 27% in-hospital mortality, respectively. INTERPRETATION: The above data emphasize that altered states of consciousness contribute substantially to morbidity and mortality in a rural African hospital. In our study sample, non infectious causes represented the leading aetiologies although HIV testing was not available at the time of the study. PMID- 21035142 TI - Multiple sclerosis and progestins: a comment to POPART'MUS. PMID- 21035143 TI - Activity-dependent conduction block in chronic inflammatory demyelinating polyneuropathy. AB - Previous studies suggested that activity-dependent conduction block (CB) contributes to weakness in chronic inflammatory demyelinating polyneuropathy (CIDP). These studies, however, investigated only one nerve segment per patient, employed cervical magnetic stimulation which may be submaximal, included nerves with extremely low compound muscle action potentials (CMAPs) which precludes assessment of CB, and lacked predefined criteria for activity-dependent CB. Obtaining more robust evidence for activity-dependent CB is important because it may be treated pharmacologically. We investigated 22 nerve segments in each of 18 CIDP patients, employed supramaximal electrical stimulation, excluded nerves with markedly reduced CMAPs, and adopted criteria for activity-dependent CB. Each nerve was tested before and immediately after 60 s of maximal voluntary contraction (MVC) of the relevant muscle. Per nerve segment we calculated segmental area ratio: (area proximal CMAP)/(area distal CMAP). Per nerve we calculated total area ratio: (area CMAP evoked at Erb's point)/(area most distally evoked CMAP). MVC induced no change in mean area ratios and no activity dependent CB according to our criteria, except for one segment. MVC induced increases in distal and proximal CMAP area and duration. In segments with demyelinative slowing, MVC induced an increase in CMAP duration prolongation. Thus, in CIDP, muscle activity induces virtually no CB, but it may increase temporal dispersion of nerve action potentials. PMID- 21035145 TI - Post-streptococcal vasculopathy with evolution to Degos' disease. AB - Degos' disease or malignant atrophic papulosis is a rare disseminated occlusive vasculopathy affecting the skin, gastrointestinal tract, central nervous system, and less often other organ systems. The exact etiology of this vasculopathy has not been established. Infections, autoimmune disease and coagulation defects have been proposed as underlying pathogenic mechanisms, but none have been confirmed. Here, we report the clinical, radiological and histopathologic features of Degos' disease in a 41-year-old man following streptococcal throat infection. Prior postulated hypothesis as post-infectious immunologic mechanism may be further supported by this case. PMID- 21035144 TI - Role of ATP synthase alpha subunit in low-dose endothelial monocyte-activating polypeptide-II-induced opening of the blood-tumor barrier. AB - This study was performed to determine whether the alpha subunit of ATP synthase (alpha-ATP synthase) on brain microvascular endothelial cells (BMECs) serves as the functional target for endothelial monocyte-activating polypeptide-II (EMAP II)-induced increase in blood-tumor barrier (BTB) permeability. Using a rat C6 glioma model, we found that low-dose (80 ng/kg) EMAP-II significantly decreased the mRNA and protein expression levels of tight junction (TJ)-related proteins claudin-5, occludin, and ZO-1 on BMECs. Meantime, radioimmunity and Western blot assay showed a significant decrease in the expression levels of cAMP and catalytic subunit of protein kinase A (PKAcs) of tumor tissues. Also, pretreatment with specific alpha-ATP synthase antibody significantly blocked the effects of EMAP-II on TJ-related proteins, cAMP, and PKAcs. In addition, double immunofluorescence assay identified that EMAP-II was co-localized with alpha-ATP synthase on BMECs. This in vivo study demonstrated that alpha subunit of ATP synthase on BMECs serves as the functional target for EMAP-II selective opening of the BTB, and that cAMP/PKA signaling transduction pathway might be involved in the modulating process. PMID- 21035146 TI - A novel mutation in CACNA1A associated with hemiplegic migraine, cerebellar dysfunction and late-onset cognitive decline. AB - Hemiplegic migraine (HM) is a rare and severe subtype of migraine with aura, characterized by some degree of hemiparesis and other aura symptoms. Mutations in three genes (CACNA1A, ATP1A2 and SCN1A) have been detected in familial and, more rarely, in sporadic cases. The disease can be complicated by permanent neurological deficits, the most frequent one being a cerebellar syndrome; in addition, mental retardation has been recognized as part of the phenotypic spectrum. Here, we report a Caucasian male with a novel CACNA1A mutation and an unusual clinical phenotype: the patient, who had had a history of only two HM attacks, sought medical advice at age 49 primarily because of increasing cognitive decline accompanied by cerebellar dysfunction. While common neurodegenerative causes were excluded, neuropsychological evaluation revealed a distinct profile of deficits of a subcortico-prefrontal type as previously reported in patients with cerebellar dysfunction. This suggests a possible causal link between cerebellar and cognitive disturbances in this patient; in addition to these pathophysiological aspects, we review of the role of the cerebellum in cognition. PMID- 21035147 TI - Ataxia in posterior circulation stroke: clinical-MRI correlations. AB - OBJECTIVE: Ataxia is characterized clinically by four signs (gait and limb ataxia, dysarthria and nystagmus). Although ataxia has been described in posterior circulation (PC) stroke series, there are no prospective studies that have investigated a possible differential role of the cerebellum or its input/outputs in causing ataxia. METHODS: Ataxia was semi-quantified according to the International Cooperative Ataxia Rating Scale (ICARS) in 92 consecutive patients with acute PC stroke. Four topographical patterns based on magnetic resonance imaging (MRI) findings were identified: picaCH pattern (posterior inferior cerebellar artery infarct); scaCH pattern (superior cerebellar artery infarct); CH/CP pattern (infarct involving both the cerebellum and the brainstem cerebellar pathways); and CP pattern (infarct involving the brainstem cerebellar pathways). RESULTS: Gait ataxia was present in 95.7%, limb ataxia in 76.1%, dysarthria in 56.5% and nystagmus in 65.2% of patients. Gait ataxia frequency did not differ between the patterns, but was significantly more severe in the CH/CP pattern than in either picaCH (P=0.0059) or CP (P=0.0065) pattern. Limb ataxia was significantly less frequent (P<0.001) and less severe (P<0.001) in picaCH pattern than other patterns. Dysarthria was less frequent in picaCH pattern than in other patterns (P=0.018) and less severe than in scaCH (P=0.0043) or CP (P=0.0047) pattern. No differences in nystagmus frequency or severity were observed across all four patterns. CONCLUSION: In PC stroke gait ataxia was almost always present, regardless of the lesion site. Limb ataxia and dysarthria were less frequent in the picaCH pattern, whereas nystagmus, when present, did not differ among the topographical patterns. PMID- 21035148 TI - Five-year follow-up with low-dose tacrolimus in patients with myasthenia gravis. AB - Myasthenia gravis (MG) is an antibody-mediated autoimmune disease of the neuromuscular junction, and prednisolone (PSL) and immunosuppressive drugs are available for treatment. Tacrolimus, a macrolide that suppresses the immune system, is used as a second-line treatment for MG. There have been several reports of the effects of tacrolimus over a few years of follow-up. Here, we report data from 9 patients with steroid-dependent generalized MG treated with low-dose tacrolimus (2-3 mg/day) for 5 years. Following treatment with tacrolimus, mean MG-activities of daily living score improved from 4.6 at baseline to 3.3 at 5 years after initiation of treatment. Mean dose of PSL could also be reduced, from 24.0 mg/day at baseline to 10.2 mg/day at 5 years, although there were no cases of total withdrawal of PSL. By contrast, 5 of the 9 patients experienced exacerbation of symptoms and transient increases in PSL dose during the 5-year period. Tacrolimus is an important option for treatment of MG; however, careful management is needed for long-term treatment with this drug. PMID- 21035149 TI - Acute limb ischemia after internal thoracic artery harvesting: a case report. PMID- 21035150 TI - A novel technique for identification of the lung intersegmental plane using dye injection into the segmental pulmonary artery. PMID- 21035151 TI - [Chemotherapy and targeted treatments in glioblastomas]. AB - BACKGROUND AND PURPOSE: We review the indications and limitations of chemotherapy in glioblastoma multiform (GBM), including the role played by alkylating and other cytotoxic agents and the increased input of clinical research on targeted agents in GBM management. METHODS: In 2005, a phase III study clearly concluded in the benefit of adding temozolomide during and after radiotherapy treatment in GBM and thus defined the new standard of treatment in this devastating disease. This schedule increased the median survival from 12.1 to 14 months and the two- and five-year survival rates from 8 to 26%, and 3 to 10%, respectively, with a good tolerance profile. Moreover, methylation of the promoter of the O6 methylguanine DNA transferase (MGMT) gene exhibits a prognostic impact independently of therapeutic schedule but may also predict the benefit of adding temozolomide to radiotherapy. However, pitfalls in MGMT determination and lack of prospective validation have to be solved before considering MGMT as a decisional marker. More recently, antiangiogenic agents including enzastaurin, cediranib, bevacizumab, and others that target mainly the VEGF pathway, have been evaluated in this highly angiogenic disease. Among them, only bevacizumab has been associated with clear anti-tumor activity, although the lack of control studies limits the impact of the results to date. CONCLUSIONS: Recent studies conducted in GBM, both in the adjuvant and recurrent setting, have changed the natural course of the disease and opened a new area of clinical research, including imaging and response evaluation, predictive markers, and other targeted therapies. PMID- 21035152 TI - Cloning, expression, site-directed mutagenesis and immunolocalization of phenylalanine ammonia-lyase in Bambusa oldhamii. AB - Phenylalanine ammonia-lyase (PAL, EC 4.3.1.5) from green bamboo was isolated and cloned from the shell of Bambusa oldhamii. The K(m) of bamboo shell PAL for L-Phe was 476 MUM, and the molecular mass of native PAL was estimated as 275 kDa and the molecular mass of a subunit was about 76 kDa, indicating that PAL from bamboo also exists as a tetramer. The optimum temperature for PAL activity was 50 degrees C and the optimal pH 9.0. The identity of the purified bamboo shell PAL was confirmed using Q-TOF tandem MS/MS de novo sequencing. Four PAL genes, designated as BoPAL1 to BoPAL4, were cloned from B. oldhamii. The open reading frames of BoPAL3 and BoPAL4 were 2142 and 2106 bp in size, respectively: BoPAL2-4 contained one intron and two exons, but no intron was found in BoPAL1. BoPAL4 expressed in Escherichia coli possessed both PAL and tyrosine ammonia-lyase activities. While recombinant wild-type PAL proteins had similar biochemical properties to the native bamboo shell PAL, both site-directed mutagenesis of BoPAL1 F133H and BoPAL2 F134H, respectively, showed decreased k(cat)/K(m) values toward L-Phe, whereas BoPAL2 F134H showed a slightly increased k(cat)/K(m) value toward L-Tyr. These data suggest other residues largely control Phe/Tyr substrate specificity. An antibody raised against the purified shell PAL was generated for histochemical studies. In bamboo shell and branch shoots, PAL was localized primarily in sclerenchyma cells. PMID- 21035153 TI - Self-reported exposure to disablism is associated with poorer self-reported health and well-being among adults with intellectual disabilities in England: a cross-sectional survey. AB - OBJECTIVES: To determine the association between exposure to disablism and the health and well-being of adults with intellectual disabilities. STUDY DESIGN: Cross-sectional survey. METHODS: Secondary analysis of data extracted from the survey of Adults with Learning Difficulties in England 2003/4. RESULTS: Both self reported exposure to bullying while at school and self-reported exposure to overt acts of disablism over the previous 12 months were associated with poorer self reported health outcomes. In the vast majority of instances, these associations were stronger for people with lower levels of material or social resources. CONCLUSIONS: Exposure to overt acts of disablism may contribute to the health inequalities experienced by people with intellectual disabilities. PMID- 21035154 TI - Common mental disorders, unemployment and welfare benefits in England. AB - OBJECTIVES: Individuals who are out of work have a higher rate of common mental disorders (CMD) than individuals who are employed. People who are unemployed in the UK are entitled to welfare benefits to alleviate financial strain. This study examined rates of CMD in individuals who were employed, unemployed and receiving various UK benefits. It also investigated associations between duration of unemployment, gender and CMD. STUDY DESIGN: An analysis of 5090 working-age participants from the Adult Psychiatric Morbidity Survey 2007, a stratified probability sample survey conducted among adults aged 16 years and over living in private households in England. METHODS: CMD was assessed using the Clinical Interview Schedule (Revised). Information was gathered on sociodemographics, employment, income, benefits and debt. Data were analysed using logistic regression. RESULTS: Risk of CMD was significantly greater in individuals classified as: unemployed; economically inactive; not working due to physical health reasons; unable to find a suitable job; receiving housing, care or sickness benefit; and receiving income support. However, risk of CMD was not significantly greater in individuals receiving jobseeker's allowance. Individuals unemployed for less than 1 year or more than 3 years had a higher risk of CMD. Some interactions with gender were significant, with associations being greater in men than women. CONCLUSIONS: Job loss events are not the only reason for unemployed people to develop CMD. The state of unemployment itself may be detrimental to mental health. Risk of CMD is increased in those who have been out of work for 3 years or more. Associations between benefits and mental health are likely to be due to social, health or economic circumstances associated with benefit eligibility. PMID- 21035155 TI - The effect of pre-hospital care for venomous snake bite on outcome in Nigeria. AB - We studied pre-hospital practices of 72 consecutive snake bite victims at a hospital in north-central Nigeria. The primary outcome assessed was death or disability at hospital discharge. Victims were predominantly male farmers, and in 54 cases (75%) the snake was identified as a carpet viper (Echis ocellatus), with the remainder unidentified. Most subjects (58, 81%) attempted at least one first aid measure after the bite, including tourniquet application (53, 74%), application (15, 21%) or ingestion (10, 14%) of traditional concoctions, bite site incision (8, 11%), black stone application (4, 5.6%), and suction (3, 4.2%). The majority (44, 61%) presented late (after 4 hours). Most (53, 74%) had full recovery at hospital discharge. Three deaths (4.2%) and thirteen (18%) disabilities (mainly tissue necrosis) occurred. The use of any first aid was associated with a longer hospital stay than no use (4.6 +/- 2.0 days versus 3.6 +/- 2.7 days, respectively, P = 0.02). The antivenom requirement was greater in subjects who had used a tourniquet (P = 0.03) and in those who presented late (P = 0.02). Topical application (Odds Ratio 15, 95% CI 1.4-708) or ingestion of traditional concoctions (OR 20, 95% CI 1.4-963) were associated with increased risk of death or disability. Ingestion and application of concoctions were associated with a longer time interval before presentation, a higher cost of hospitalization, and an increased risk of wound infection. PMID- 21035157 TI - Explicit model for ultrasonic attenuation in equiaxial hexagonal polycrystalline materials. AB - Attenuation coefficients for longitudinal and transverse ultrasonic waves are obtained in explicit form for untextured hexagonal polycrystalline materials. The equations obtained are easy to use for interpretation and evaluation of experimental results for ultrasonic characterization of microstructures. The attenuation coefficients are separated into two terms, corresponding to incident wave scattering into longitudinal and transverse waves. It is shown that the general expressions for attenuation coefficients in the long wavelength (Rayleigh) and short wavelength (stochastic) regimes transit to the known classical asymptotics. Simple equations to estimate the frequency range of the transition from the Rayleigh to stochastic regimes are also given. An example of experimental measurements in Ti alloy is provided to illustrate application of the model; the results show reasonable agreement between the experiment and the model with no adjustable parameters. PMID- 21035156 TI - Targeting gastrin-releasing peptide as a new approach to treat aggressive refractory neuroblastomas. AB - BACKGROUND: The overall survival for neuroblastoma remains dismal, in part due to the emergence of resistance to chemotherapeutic drugs. We have demonstrated that gastrin-releasing peptide (GRP), a gut peptide secreted by neuroblastoma, acts as an autocrine growth factor. We hypothesized that knockdown of GRP will induce apoptosis in neuroblastoma cells and potentiate the cytotoxic effects of chemotherapeutic agents. METHODS: The human neuroblastoma cell lines (JF, SK-N SH) were transfected with small interfering (si) RNA targeted at GRP. Apoptosis was assessed by DNA fragmentation assay. Immunoblotting was used to confirm molecular markers of apoptosis, and flow cytometry was performed to determine cell cycle arrest after GRP knockdown. RESULTS: siGRP resulted in an increase in apoptosis in the absence of chemotherapeutic interventions. A combination of GRP silencing and chemotherapeutic drugs resulted in enhanced apoptosis when compared to either of the treatments alone. GRP silencing led to increased expression of proapoptotic proteins, p53 and p21. CONCLUSION: Silencing of GRP induces apoptosis in neuroblastoma cells; it acts synergistically with chemotherapeutic effects of etoposide and vincristine. GRP knockdown-mediated apoptosis appears to be associated with upregulation of p53 in neuroblastoma cells. Targeting GRP may be postulated as a potential novel agent for combinational treatment to treat aggressive neuroblastomas. PMID- 21035158 TI - betaC1 encoded by tomato yellow leaf curl China betasatellite forms multimeric complexes in vitro and in vivo. AB - The betaC1 protein encoded by betasatellites associated with begomoviruses is multi-functional. To investigate its properties, the betaC1 protein encoded by tomato yellow leaf curl China betasatellite (TYLCCNB) was expressed in Escherichia coli and analyzed for its ability to self-interaction. The betaC1 protein formed large soluble multimeric complexes in vitro and in vivo. Mutations that prevented formation of multimeric complexes in vitro, also prevented formation of granular bodies in vivo, suggesting that granular bodies resulted from betaC1 oligomerization. Similarly, betaC1 mutants unable to form complexes also did not induce typical symptoms in plants when expressed from a Potato virus X (PVX) vector, suggesting that betaC1 self-interaction was required for symptom induction in planta. Deletion analysis revealed that amino acid sequences spanning two predicted alpha-helices at the C-terminal end of the protein were important in multimerization. PMID- 21035159 TI - Early gene expression events in ferrets in response to SARS coronavirus infection versus direct interferon-alpha2b stimulation. AB - Type I interferons (IFNs) are essential to the clearance of viral diseases, however, a clear distinction between genes upregulated by direct virus-cell interactions and genes upregulated by secondary IFN production has not been made. Here, we investigated differential gene regulation in ferrets upon subcutaneous administration of IFN-alpha2b and during SARS-CoV infection. In vivo experiments revealed that IFN-alpha2b causes STAT1 phosphorylation and upregulation of abundant IFN response genes (IRGs), chemokine receptors, and other genes that participate in phagocytosis and leukocyte transendothelial migration. During infection with SARS-CoV not only a variety of IRGs were upregulated, but also a significantly broader range of genes involved in cell migration and inflammation. This work allowed dissection of several molecular signatures present during SARS CoV which are part of a robust IFN antiviral response. These signatures can be useful markers to evaluate the status of IFN responses during a viral infection and specific features of different viruses. PMID- 21035160 TI - TCR triggering transcriptionally downregulates CCR5 expression on rhesus macaque CD4(+) T-cells with no measurable effect on susceptibility to SIV infection. AB - Studies using transformed human cell lines suggest that most SIV strains use CCR5 as co-receptor. Our analysis of primary rhesus macaque CD4(+) T-cell clones revealed marked differences in susceptibility to SIV(mac)239 infection. We investigated whether different levels of CCR5 expression account for clonal differences in SIV(mac)239 susceptibility. Macaque CD4(+) T-cells showed significant CCR5 downregulation 1-2days following CD3 mAb stimulation, which gradually recovered at resting state, 7-10days after activation. Exposure of clones to SIV(mac)239 during their CCR5(low) or CCR5(high) expression states revealed differences in SIV susceptibility independent of surface CCR5 levels. Furthermore, a CCR5 antagonist similarly reduced SIV(mac)239 infection of clones during their CCR5(low) or CCR5(high) expression states. Our data suggest a model where i) very low levels of CCR5 are sufficient for efficient SIV infection, ii) CCR5 levels above this threshold do not enhance infection, and iii) low level infection can occur in the absence of CCR5. PMID- 21035162 TI - Human Trim5alpha has additional activities that are uncoupled from retroviral capsid recognition. AB - Trim5alpha is a host antiviral protein that recognizes incoming retroviral capsids in the cytoplasm and prevents productive infections. Although present in most mammals, the state of the Trim5 gene is dynamic in that primates have one copy with several splice variants, while rodents and cows have multiple copies. Mouse Trim30 (one of the mouse Trim5alpha homologs) has been shown to negatively regulate NF-kappaB activation by targeting upstream signaling intermediates TAB2 and TAB3 for degradation. We show that human Trim5alpha also affects levels of TAB2, resulting in abrogation of TAB2-dependent NF-kappaB activation. Surprisingly, unlike mouse Trim30, human and rhesus Trim5alpha are able to activate NF-kappaB-driven reporter gene expression in a dose-dependent manner. We show that Trim5alpha uses distinct domains for the distinct abilities of affecting TAB2 levels, regulating NF-kappaB, and recognizing retroviral capsids. Our results demonstrate functions of Trim5alpha that are not dependent on recognizing the retroviral capsid. PMID- 21035161 TI - Deficient incorporation of spike protein into virions contributes to the lack of infectivity following establishment of a persistent, non-productive infection in oligodendroglial cell culture by murine coronavirus. AB - Infection of mouse oligodendrocytes with a recombinant mouse hepatitis virus (MHV) expressing a green fluorescence protein facilitated specific selection of virus-infected cells and subsequent establishment of persistence. Interestingly, while viral genomic RNAs persisted in infected cells over 14 subsequent passages with concomitant synthesis of viral subgenomic mRNAs and structural proteins, no infectious virus was isolated beyond passage 2. Further biochemical and electron microscopic analyses revealed that virions, while assembled, contained little spike in the envelope, indicating that lack of infectivity during persistence was likely due to deficiency in spike incorporation. This type of non-lytic, non productive persistence in oligodendrocytes is unique among animal viruses and resembles MHV persistence previously observed in the mouse central nervous system. Thus, establishment of such a culture system that can recapitulate the in vivo phenomenon will provide a powerful approach for elucidating the mechanisms of coronavirus persistence in glial cells at the cellular and molecular levels. PMID- 21035163 TI - Growth, photosynthesis and antioxidant responses of two microalgal species, Chlorella vulgaris and Selenastrum capricornutum, to nonylphenol stress. AB - The effect of nonylphenol (NP) on growth, photochemistry and biochemistry of two green microalgae, Chlorella vulgaris and Selenanstrum capricornutum, and their ability to degrade NP were compared. The 96 h EC50 of C. vulgaris and S. capricornutum were greater than 4.0 and 1.0 mg L(-1) NP, respectively, suggesting that the former species was more tolerant to NP. Both microalgae acclimated to NP stress through down-regulating their photosynthetic activities, including antenna size (chlorophyll a content), maximal photochemistry (Fv/Fm) and the light absorbed by PSII (ABS/CS0), but the dissipation of energy from reaction centres (DI0/RC) increased with the increase of NP concentrations. In C. vulgaris, the changes of these parameters were more significant than in S. capricornutum and recovered completely after a 96 h exposure. The antioxidant responses, such as GSH content, CAT and POD activities in C. vulgaris increased with the increase of NP concentrations after a 24h exposure, but these changes disappeared with exposure time and recovered to the control levels after 96 h. In S. capricornutum, although GSH content, CAT and POD activities also increased when exposed to low- to moderate-NP concentrations, these values were significantly reduced at a high concentration (4 mg L(-1)) even after a 96 h exposure, indicating its antioxidant responses were significantly delayed. It is clear that the more NP-tolerant species, C. vulgaris, acclimated better with a faster recovery of its photosynthetic activity from the NP-induced damage, and exhibited more efficient and rapid responses to NP-induced oxidative stress. C. vulgaris also had a higher NP degradation ability than S. capricornutum. PMID- 21035164 TI - Toxicity and bioaccumulation of biosolids-borne triclocarban (TCC) in terrestrial organisms. AB - Triclocarban (TCC) toxicity and bioaccumulation data are primarily limited to direct human and animal dermal exposures, animal ingestion exposures to neat and feed-spiked TCC, and/or aquatic organism exposures. Three non-human, terrestrial organism groups anticipated to be the most highly exposed to land-applied, biosolids-borne TCC are soil microbes, earthworms, and plants. The three ecological receptors are expected to be at particular risk due to unique modes of exposure (e.g. constant, direct contact with soil; uptake of amended soil and pore water), inherently greater sensitivity to environmental contaminants (e.g. increased body burdens, permeable membranes), and susceptibility to minute changes in the soil environment. The toxicities of biosolids-borne TCC to Eisenia fetida earthworms and soil microbial communities were characterized using adaptations of the USEPA Office of Prevention, Pesticides, and Toxic Substances (OPPTS) Guidelines 850.6200 (Earthworm Subchronic Toxicity Test) and 850.5100 (Soil Microbial Community Toxicity Test), respectively. The resultant calculated TCC LC50 value for E. fetida was 40 mg TCC kg amended fine sand(-1). Biosolids borne TCC in an amended fine sand had no significant effect on soil microbial community respiration, ammonification, or nitrification. Bioaccumulation of biosolids-borne TCC by E. fetida and Paspulum notatum was measured to characterize potential biosolids-borne TCC movement through the food chain. Dry weight TCC bioaccumulation factor (BAF) values in E. fetida and P. notatum ranged from 5.2-18 and 0.00041-0.007 (gsoil gtissue(-1)), respectively. PMID- 21035165 TI - The toxicity of composted sediments from Mediterranean ports evaluated by several bioassays. AB - This work investigates the ecotoxicological evaluation of contaminated dredged sediments from French Mediterranean navy harbour (A), commercial port (B) and two composite specimens (C) and (D) coming from the mixture of A and B with other port sediments. The toxicity of elutriates from these sediments is estimated using embryo-toxicity test, Microtox(r) solid phase test, LuminoTox, phytotoxicity tests and genotoxicity test. Bioassay responses are not clearly correlated with chemical contamination in the whole sediment and vary as a function of tested organisms. The highest contaminated samples (A and C) are almost always more toxic than the less contaminated samples (B and D). Among composite sediments, the mixture effect with other sediments is not efficient to decrease toxicity in sample C, suggesting that other parameters influence toxicity level such as particle size or organic matter content. These parameters should be taken into consideration in order to improve the efficiency of the mixture process and produce composite sediments with low toxicity. PMID- 21035167 TI - Pathology subspecialty fellowship application reform 2007 to 2010. AB - The specialty of Pathology and Laboratory Medicine has entered into a phase when the 4-year sequence of Anatomic Pathology and/or Clinical Pathology Residency Training is almost universally followed by 1 or more years of Subspecialty Fellowship Training. Such training may occur in one of the American Board of Pathology-recognized subspecialties or any number of "subspecialty fellowships" that, although not leading to subspecialty board certification, may nevertheless fall under the oversight of the local institutional Graduate Medical Education Committee and the Accreditation Council for Graduate Medical Education Review Committee for Pathology. Unlike the application process for first-year Pathology Residency, which is run through the National Resident Matching Program, applications for Subspecialty Pathology Fellowships are not coordinated by any consistent schedule. Competition for Subspecialty Pathology Fellowships has consistently resulted in undesirable drift of the fellowship application process to dates that are unacceptably early for many fellowship applicants. Responding to widespread dissatisfaction voiced by national pathology resident organizations, in 2007, the Association of Pathology Chairs began evaluation and potential intervention in the fellowship application process. Three years of intermittently intense discussion, surveys, and market analysis, have led the Council of the Association of Pathology Chairs to recommend implementation of a Pathology Subspecialty Fellowship Matching program starting in the 2011 to 2012 recruiting year, for those Applicants matriculating in fellowship programs July 2013. We report on the data that informed this decision and discuss the pros and cons that are so keenly felt by the stakeholders in this as-yet-incomplete reform process. PMID- 21035166 TI - Parathion degradation and its intermediate formation by Fenton process in neutral environment. AB - The purpose of this study is to investigate parathion degradation by Fenton process in neutral environment. The initial parathion concentration for all the degradation experiments was 20 ppm. For hydrogen ion effect on Fenton degradation, the pH varied from 2 to 8 at the [H2O2] to [Fe2(+)] ratio of 2-2 mM, and the result showed pH 3 as the most effective environment for parathion degradation by Fenton process. Apparent degradation was also observed at pH 7. The subsequent analysis for parathion degradation was conducted at pH 7 because most environmental parathion exists in the neutral environment. Comparing the parathion degradation results at various Fenton dosages revealed that at Fe2(+) concentrations of 0.5, 1.0 and 1.5 mM, the Fenton reagent ratio ([H2O2]/[Fe2(+)]) for best-removing performance were found as 4, 3, and 2, resulting in the removal efficiencies of 19%, 48% and 36%, respectively. Further increase in Fe2(+) concentration did not cause any increase of the optimum Fenton reagent ratio for the best parathion removal. The result from LC-MS also indicated that hydroxyl radicals might attack the PS double bond, the single bonds connecting nitro group, nitrophenol, or the single bond within ethyl groups of parathion molecules forming paraoxons, nitrophenols, nitrate/nitrite, thiophosphates, and other smaller molecules. Lastly, the parathion degradation by Fenton process at the presence of humic acids was investigated, and the results showed that the presence of 10 mg L-1 of humic acids in the aqueous solution enhanced the parathion removal by Fenton process twice as much as that without the presence of humic acids. PMID- 21035168 TI - Interaction between chronic arsenic exposure via drinking water and plasma lactate dehydrogenase activity. AB - Arsenic is a potent environmental pollutant that has caused one of the largest public health poisonings in the history of human civilization, affecting tens of millions of people worldwide especially in Bangladesh. Lactate dehydrogenase (LDH) in blood plays an important role in predicting cell or organ damage and as an important clue to the diagnosis of a variety of cancers. However, effect of chronic arsenic exposure on the LDH level in blood has not yet been documented. Since the chronic arsenic exposure is associated with organ damages and multi site cancers, this research aimed at assaying the plasma level of LDH activity in the population who were exposed to arsenic chronically in Bangladesh. A total of 185 individuals living in arsenic-exposed areas and 121 individuals living in non exposed area in Bangladesh were recruited as study subjects. Arsenic content in drinking water, hair and nails were estimated by Inductively Coupled Plasma Mass Spectroscopy (ICP-MS) and LDH activity was assayed by a spectrophotometer. Significant increase in LDH activity was observed with increasing concentrations of arsenic in water, hair and nails. Further, the study subjects were split into four groups based on the three ways of each exposure metrics (water, hair and nail arsenic concentrations) where the study subjects in the non-exposed area were used as a reference (lowest exposure) group. LDH activity was found to be increased in the higher exposure groups of water and hair arsenic concentrations. LDH activity was also increased at low to medium exposure groups of nail arsenic concentrations.Thus, the elevated plasma LDH activity might be helpful for the early prognosis of organ or tissue damage in the individuals who were exposed to arsenic chronically. PMID- 21035169 TI - Priority water research questions as determined by UK practitioners and policy makers. AB - Several recent studies have emphasised the need for a more integrated process in which researchers, policy makers and practitioners interact to identify research priorities. This paper discusses such a process with respect to the UK water sector, detailing how questions were developed through inter-disciplinary collaboration using online questionnaires and a stakeholder workshop. The paper details the 94 key questions arising, and provides commentary on their scale and scope. Prioritization voting divided the nine research themes into three categories: (1) extreme events (primarily flooding), valuing freshwater services, and water supply, treatment and distribution [each >150/1109 votes]; (2) freshwater pollution and integrated catchment management [100-150 votes] and; (3) freshwater biodiversity, water industry governance, understanding and managing demand and communicating water research [50-100 votes]. The biggest demand was for research to improve understanding of intervention impacts in the water environment, while a need for improved understanding of basic processes was also clearly expressed, particularly with respect to impacts of pollution and aquatic ecosystems. Questions that addressed aspects of appraisal, particularly incorporation of ecological service values into decision making, were also strongly represented. The findings revealed that sustainability has entered the lexicon of the UK water sector, but much remains to be done to embed the concept operationally, with key sustainability issues such as resilience and interaction with related key sectors, such as energy and agriculture, relatively poorly addressed. However, the exercise also revealed that a necessary condition for sustainable development, effective communication between scientists, practitioners and policy makers, already appears to be relatively well established in the UK water sector. PMID- 21035171 TI - Screening history in women with cervical cancer in a Danish population-based screening program. AB - OBJECTIVE: The aim of this study was to explore the screening histories of all cervical cancers in a Danish screening population. The intention was to decide suboptimal sides of the screening program and to evaluate the significance of routine screening in the development of cervical cancer. METHODS: The study describes the results of a quality control audit, performed on all new cervical cancer cases diagnosed in the years 2008-2009 at two major Danish screening centers. All relevant cytological and histological cervical samples were reviewed. RESULTS: 202.534 cytological samples were evaluated in the study period, while 112 women were diagnosed with cervical cancer. The histological diagnoses comprised: 62 (55.4%) squamous cell carcinomas, 20 (17.9%) microinvasive squamous cell carcinomas, 25 (22.3%) adenocarcinomas and 5 cancers of different histology. The mean age of study subjects was 46.6 years. 51 (45.5%) women had deficient screening histories, while 45 (40.2%) women had followed the screening recommendations and had normal cervical samples in review. 11 (9.8%) women were diagnosed with false negative cytology, 2 women had false negative histological tests, while pathological review was not feasible for 3 subjects. CONCLUSIONS: More than 45% of the cervical cancer cases in our study were due to deficient cervical screening, stressing the importance of increasing the screening-uptake and coverage. 40% interval cancers emphasize the relevance of further cervical testing of women with relevant symptoms, despite of prior normal cervical samples. Finally, 9.8% false negative cytological samples are consistent with previous reports, but still a part of the screening program that should be improved. PMID- 21035170 TI - Overexpression of gelsolin in human cervical carcinoma and its clinicopathological significance. AB - OBJECTIVES: Cervical carcinoma is the second most common cause of death from gynecological cancers worldwide. Knowledge of the molecular mechanisms underlying the tumorigenesis of cervical cancer cell, except human papilloma virus infection, is limited. METHODS: A microarray was used to study the differential expression of genes in cancerous tissues to identify new molecular markers for diagnosis and prognosis. Their differential expression was confirmed with Western blotting and immunohistochemical analyses. The clinical correlations and prognostic significance of the aberrantly expressed proteins were evaluated to identify novel biomarkers of cervical cancer. RESULTS: The expression of gelsolin was significantly upregulated in 78% of patients with cervical cancer, and gelsolin was selected for further study. Gelsolin expression was stronger in cervical tumor tissues than in the surrounding noncancerous tissues (P<0.001). Gelsolin expression in the plasma of cervical cancer patients was increased 2.2 fold compared with that of healthy control subjects (P<0.001). The levels of plasma gelsolin in the early and late stages were significantly different (P=0.006). According to immunohistochemical analysis, increased gelsolin expression was associated with histological type and FIGO stage II. The 5-year overall survival and recurrence-free survival rates for the low-expression group (cut-off=115) were significantly higher than those of the high-expression group. Cancer cells with reduced gelsolin expression exhibited reduced migration and proliferation. CONCLUSIONS: These results provide strong evidence that gelsolin plays an important role in cellular proliferation and migration in cervical cancer and suggest that gelsolin is a promising marker for cervical cancer screening and prognosis. PMID- 21035172 TI - The expression of the miRNA-200 family in endometrial endometrioid carcinoma. AB - OBJECTIVE: Recent reports suggest that targeting the unique miRNAs highly expressed in several cancers may be a promising approach in the development of new cancer therapeutic tools. The purpose of this study was to evaluate the roles of miRNAs as therapeutic targets in human endometrial endometrioid carcinomas (EECs). METHODS: We evaluated the differential expressions of miRNAs in EECs and normal endometrial tissues using microarrays and cluster analysis. After validation of differentially expressed miRNAs in another set of EECs and normal endometrial tissues, we performed the in vitro experiment using endometrial cancer cells with anti-miRNA (anti-miR) to evaluate the roles of miRNAs that are highly expressed in EECs for cell proliferation and chemosensitivity. RESULTS: A miRNA microarray showed that the miR-200 family, including hsa-miR-141, hsa-miR 200a, hsa-miR-200b, hsa-miR-200c, and hsa-miR-429, was up-regulated in EECs as compared with that in normal endometrial tissues. When we treated endometrial cancer cells with specific anti-miRs, including anti-miR-141, -200a, -200b, 200c, or -429, we found that anti-miR-200a, -200b, -200c, and -429 significantly inhibited the growth of HEC-1A cells and anti-miR-141, -200c, and -429 significantly inhibited the growth of Ishikawa cells. Moreover, transfection with anti-miR-429 enhanced the cytotoxic effect of cisplatin in HEC-1A cells. CONCLUSIONS: These results indicate that the miR-200 family is highly expressed in EECs compared with that of normal endometrial tissues and could play an important role in cancer growth. Specifically, anti-miR-429 could enhance the cytotoxic activity with cisplatin in EECs. Therefore, the miR-200 family may offer new candidate targets to be exploited in therapeutic strategies for patients with these carcinomas. PMID- 21035173 TI - Application of hTERC in thinprep samples with mild cytologic abnormality and HR HPV positive. AB - OBJECTIVE: Amplification of hTERC is found to be an important genetic event in the progression from cervical dysplasia to cervical cancer. The hTERC value in predicting high-grade cervical intraepithelial neoplasia (CIN) or squamous cell carcinoma (SCC), in high-risk HPV (HR-HPV) positive thinprep samples with atypical squamous cells (ASC) or a low-grade squamous intraepithelial lesion (LSIL) was explored in this study. METHODS: A total of 300 thinprep cytology specimens (129 of ASC-US, 82 of LSIL, and 89 of ASC-H) with positive HR-HPV DNA was detected by a two-probe dual-color FISH panel, targeting hTERC and the centromeric region of chromosome 3 (CSP3). Using >2 signals for hTERC together with >=2 signals for CSP3 to define abnormal nucleus, and the cutoff value was set at 6.5 per random 200 nuclei displayed increased hTERC signals and/or tumor ploidy. Statistical analyses were based on histologic findings of colposcopy biopsies, allowing CIN2 or worse (CIN2+) as the positive criterion. RESULTS: The FISH results were systematically analyzed among groups, based on histologic diagnosis, cytologic finding, HR-HPV viral load, and age status. hTERC presented good consistency with histology, and had satisfactory sensitivity, specificity, and accuracy among different groups, with less difference intergroup. The individual hTERC positive nuclei ratio was generally increased with severity of the cervical lesions. CONCLUSIONS: hTERC could be a stable predictor in assuring the risk of high-grade CIN in women with mild cytologic abnormality and positive HR-HPV, and the individual positive nuclei ratio of it might be helpful in identifying morbid grade for cervical lesions. PMID- 21035174 TI - Interaction between preoperative CA-125 level and survival benefit of neoadjuvant chemotherapy in advanced epithelial ovarian cancer. AB - OBJECTIVE: This study aims to determine whether neoadjuvant chemotherapy (NAC) has survival benefit in selected patients with advanced epithelial ovarian cancer (EOC) who have high risk of suboptimal cytoreduction which is represented by high serum CA-125 level. METHODS: We retrospectively reviewed records of 314 patients with EOC including 94 patients who received NAC. After stratification by preoperative CA-125 levels, the progression-free survival (PFS) was compared between the NAC group and the primary debulking surgery (PDS) group. RESULTS: The NAC group had more FIGO stage IV disease (P<0.001) and higher CA-125 levels (P<0.001). Although suboptimal resection rate was higher in the PDS group (50% vs. 18%, P<0.001), however, NAC was not associated with increased PFS in multivariate Cox analysis (P=0.334). Nevertheless, after stratification according to CA-125 levels, NAC showed survival benefit in the subgroup with high CA-125 levels (>2000 U/ml; HR 0.62, P=0.037). CONCLUSION: Our preliminary data suggests the possible interaction between CA-125 levels and survival benefit of NAC. The randomized trial data about NAC should be stratified by the reproducible and relevant criteria such as preoperative serum CA-125 level to elucidate true survival benefit of NAC in ovarian cancer. PMID- 21035175 TI - The role of penicillin in benign skin rashes in childhood: a prospective study based on drug rechallenge. AB - BACKGROUND: Delayed-onset urticarial or maculopapular rashes are frequently observed in children treated with beta-lactams. Many are labeled "allergic" without reliable testing. OBJECTIVE: Determine the etiology of these rashes by exploring both infectious and allergic causes. METHODS: Children presenting to the emergency department with delayed-onset urticarial or maculopapular rashes were enrolled. Acute and convalescent sera were obtained for viral screening along with a throat swab. Subjects underwent intradermal and patch skin testing for beta-lactams 2 months after presentation. Anti-beta-lactam blood allergy tests were also obtained. All subjects underwent an oral challenge test (OCT) with the culprit antibiotic. RESULTS: Eighty-eight children were enrolled between 2006 and 2008. There were 11 (12.5%) positive intradermal and no positive patch tests. There were 2 (2.3%) positive blood allergy tests. There were 6 (6.8%) subjects with a positive OCT, 2 were intradermal-negative, and 4 were intradermal positive. No OCT reactions were more severe than the index event. Most subjects had at least 1 positive viral study, 54 (65.9%) in the OCT negative group. CONCLUSION: In this situation, beta-lactam allergy is clearly overdiagnosed because the skin rash is only rarely reproducible (6.8%) by a subsequent challenge. Viral infections may be an important factor in many of these rashes. OCTs were positive in a minority of intradermal skin test-positive subjects. Patch testing and blood allergy testing provided no useful information. OCTs should be considered in all children who develop a delayed-onset urticarial or maculopapular rash during treatment with a beta-lactam. PMID- 21035176 TI - Mast cell activation syndrome: Proposed diagnostic criteria. AB - The term mast cell activation syndrome (MCAS) is finding increasing use as a diagnosis for subjects who present with signs and symptoms involving the dermis, gastrointestinal track, and cardiovascular system frequently accompanied by neurologic complaints. Such patients often have undergone multiple extensive medical evaluations by different physicians in varied disciplines without a definitive medical diagnosis until the diagnosis of MCAS is applied. However, MCAS as a distinct clinical entity has not been generally accepted, nor do there exist definitive criteria for diagnosis. Based on current understanding of this disease "syndrome" and on what we do know about mast cell activation and resulting pathology, we will explore and propose criteria for its diagnosis. The proposed criteria will be discussed in the context of other disorders involving mast cells or with similar presentations and as a basis for further scientific study and validation. PMID- 21035177 TI - Maternal consumption of peanut during pregnancy is associated with peanut sensitization in atopic infants. AB - BACKGROUND: Peanut allergy is typically severe, lifelong, and prevalent. OBJECTIVE: To identify factors associated with peanut sensitization. METHODS: We evaluated 503 infants 3 to 15 months of age (mean, 9.4 months) with likely milk or egg allergy but no previous diagnosis of peanut allergy. A total of 308 had experienced an immediate allergic reaction to cow's milk and/or egg, and 204 had moderate to severe atopic dermatitis and a positive allergy test to milk and/or egg. A peanut IgE level >=5 kU(A)/L was considered likely indicative of peanut allergy. RESULTS: A total of 140 (27.8%) infants had peanut IgE levels >=5 kU(A)/L. Multivariate analysis including clinical, laboratory, and demographic variables showed frequent peanut consumption during pregnancy (odds ratio, 2.9; 95% CI, 1.7-4.9; P < .001), IgE levels to milk (P = .001) and egg (P < .001), male sex (P = .02), and nonwhite race (P = .02) to be the primary factors associated with peanut IgE >=5 kUA/L. Frequency of peanut consumption during pregnancy and breast-feeding showed a dose-response association with peanut IgE >=5 kU(A)/L, but only consumption during pregnancy was a significant predictor. Among 71 infants never breast-fed, frequent consumption of peanut during pregnancy was strongly associated with peanut IgE >=5 kU(A)/L (odds ratio, 4.99, 95% CI, 1.69-14.74; P < .004). CONCLUSION: In this cohort of infants with likely milk or egg allergy, maternal ingestion of peanut during pregnancy was strongly associated with a high level of peanut sensitization. PMID- 21035178 TI - Extensive in vivo metabolite-protein interactions revealed by large-scale systematic analyses. AB - Natural small compounds comprise most cellular molecules and bind proteins as substrates, products, cofactors, and ligands. However, a large-scale investigation of in vivo protein-small metabolite interactions has not been performed. We developed a mass spectrometry assay for the large-scale identification of in vivo protein-hydrophobic small metabolite interactions in yeast and analyzed compounds that bind ergosterol biosynthetic proteins and protein kinases. Many of these proteins bind small metabolites; a few interactions were previously known, but the vast majority are new. Importantly, many key regulatory proteins such as protein kinases bind metabolites. Ergosterol was found to bind many proteins and may function as a general regulator. It is required for the activity of Ypk1, a mammalian AKT/SGK kinase homolog. Our study defines potential key regulatory steps in lipid biosynthetic pathways and suggests that small metabolites may play a more general role as regulators of protein activity and function than previously appreciated. PMID- 21035179 TI - Biodegradable collagen patch with covalently immobilized VEGF for myocardial repair. AB - Vascularization of engineered tissues in vitro and in vivo remains a key problem in translation of engineered tissues to clinical practice. Growth factor signalling can be prolonged by covalent tethering, thus we hypothesized that covalent immobilization of vascular endothelial growth factor (VEGF-165) to a porous collagen scaffold will enable rapid vascularization in vivo. Covalent immobilization may be preferred over controlled release or cell transfection if the effects are desired within the biomaterial rather than the surrounding tissue. Scaffolds were prepared with 14.5 +/- 1.4 ng (Low) or 97.2 +/- 8.0 ng (High) immobilized VEGF, or left untreated (control), and used to replace a full right ventricular free wall defect in rat hearts. In addition to rapid vascularization, an effective cardiac patch should exhibit neither thinning nor dilatation upon implantation. In vitro, VEGF enhanced the growth of endothelial and bone marrow cells seeded onto scaffolds. In vivo, High VEGF patches had greater blood vessel density (p < 0.01) than control at Day 7 and 28 due to increased cell recruitment and proliferation (p < 0.05 vs. control). At Day 28, VEGF-treated patches were significantly thicker (p < 0.05) than control, and thickness correlated positively with neovascularization (r = 0.67, p = 0.023). Importantly, angiogenesis in VEGF scaffolds contributed to improved cell survival and tissue formation. PMID- 21035180 TI - Volumetric interpretation of protein adsorption: interfacial packing of protein adsorbed to hydrophobic surfaces from surface-saturating solution concentrations. AB - The maximum capacity of a hydrophobic adsorbent is interpreted in terms of square or hexagonal (cubic and face-centered-cubic, FCC) interfacial packing models of adsorbed blood proteins in a way that accommodates experimental measurements by the solution-depletion method and quartz-crystal-microbalance (QCM) for the human proteins serum albumin (HSA, 66 kDa), immunoglobulin G (IgG, 160 kDa), fibrinogen (Fib, 341 kDa), and immunoglobulin M (IgM, 1000 kDa). A simple analysis shows that adsorbent capacity is capped by a fixed mass/volume (e.g. mg/mL) surface region (interphase) concentration and not molar concentration. Nearly analytical agreement between the packing models and experiment suggests that, at surface saturation, above-mentioned proteins assemble within the interphase in a manner that approximates a well-ordered array. HSA saturates a hydrophobic adsorbent with the equivalent of a single square or hexagonally-packed layer of hydrated molecules whereas the larger proteins occupy two-or-more layers, depending on the specific protein under consideration and analytical method used to measure adsorbate mass (solution depletion or QCM). Square or hexagonal (cubic and FCC) packing models cannot be clearly distinguished by comparison to experimental data. QCM measurement of adsorbent capacity is shown to be significantly different than that measured by solution depletion for similar hydrophobic adsorbents. The underlying reason is traced to the fact that QCM measures contribution of both core protein, water of hydration, and interphase water whereas solution depletion measures only the contribution of core protein. It is further shown that thickness of the interphase directly measured by QCM systematically exceeds that inferred from solution-depletion measurements, presumably because the static model used to interpret solution depletion does not accurately capture the complexities of the viscoelastic interfacial environment probed by QCM. PMID- 21035182 TI - Human embryonic stem cell-derived microvascular grafts for cardiac tissue preservation after myocardial infarction. AB - We present use of a synthetic, injectable matrix metalloproteinase (MMP) responsive, bioactive hydrogel as an in situ forming scaffold to deliver thymosin beta4 (Tbeta4), a pro-angiogenic and pro-survival factor, along with vascular cells derived from human embryonic stem cells (hESC) in ischemic injuries to the heart in a rat model. The gel was found to substitute the degrading extracellular matrix in the infarcted myocardium of rats and to promote structural organization of native endothelial cells, while some of the delivered hESC-derived vascular cells formed de novo capillaries in the infarct zone. Magnetic resonance imaging (MRI) revealed that the microvascular grafts effectively preserved contractile performance 3 d and 6 wk after myocardial infarction, attenuated left ventricular dilation, and decreased infarct size as compared to infarcted rats treated with PBS injection as a control (3 d ejection fraction, + ~7%, P < 0.001; 6 wk ejection faction, + ~12%, P < 0.001). Elevation in vessel density was observed in response to treatment, which may be due in part to elevations in human (donor) derived cytokines EGF, VEGF and HGF (1 d). Thus, a clinically relevant matrix for dual delivery of vascular cells and drugs may be useful in engineering sustained tissue preservation and potentially regenerating ischemic cardiac tissue. PMID- 21035181 TI - Enhancement of peptide coupling to hydroxyapatite and implant osseointegration through collagen mimetic peptide modified with a polyglutamate domain. AB - Hydroxyapatite (HA) is a widely-used biomaterial for bone repair due to its high degree of osteoconductivity. However, strategies for improving HA performance by functionalizing surfaces with bioactive factors are limited. In this study, we explored the use of a HA-binding domain (heptaglutamate, "E7") to facilitate coupling of the collagen mimetic peptide, DGEA, to two types of HA-containing materials, solid HA disks and electrospun polycaprolactone matrices incorporating nanoparticulate HA. We found that the E7 domain directed significantly more peptide to the surface of HA and enhanced peptide retention on both materials in vitro. Moreover, E7-modified peptides were retained in vivo for at least two months, highlighting the potential of this mechanism as a sustained delivery system for bioactive peptides. Most importantly, E7-DGEA-coupled HA, as compared with DGEA-HA, enhanced the adhesion and osteoblastic differentiation of mesenchymal stem cells, and also increased new bone formation and direct bone implant contact on HA disks implanted into rat tibiae. Collectively, these results support the use of E7-DGEA peptides to promote osteogenesis on HA substrates, and further suggest that the E7 domain can serve as a universal tool for anchoring a wide variety of bone regenerative molecules to any type of HA containing material. PMID- 21035183 TI - The cell labeling efficacy, cytotoxicity and relaxivity of copper-activated MRI/PET imaging contrast agents. AB - A new class of nanoparticle-based dual-modality positron emission tomography/magnetic resonance imaging (PET/MRI) contrast agents has been developed. The probe consists of a superparamagnetic iron oxide (SPIO) or manganese oxide core coated with 3,4-dihydroxy-D,L-phenylalanine (DL-DOPA). The chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) was conjugated to DOPA termini. The DOTA modified nanoparticles allow chelation of copper for PET imaging. These surface functionalized nanoparticle-based probes have been characterized by various analytical techniques. The cell-labeling efficacy, cytotoxicity and relaxivity of these nanoparticles have been evaluated and compared with the same properties of one of the most commonly utilized MRI contrast agents, Feridex((r)). Evidently, this new nanoparticle has a great potential for use in cell tracking with MRI and PET in the absence of transfecting agent. It is noteworthy that there is a sharp increase in r(2) relaxivity of these nanoparticles on coordination with Cu(2+) ions. Thus these iron oxide nanoparticles can also be explored as the smart magnetic resonance (MR) sensor for the detection of micromolar changes in copper concentration for neurodegenerative diseases such as Alzheimer's disease, Menkes and Wilson's diseases, amyotrophic lateral sclerosis and prion diseases. PMID- 21035184 TI - The use of hydrogel microparticles to sequester and concentrate bacterial antigens in a urine test for Lyme disease. AB - Hydrogel biomarker capturing microparticles were evaluated as a biomaterial to amplify the sensitivity of urine testing for infectious disease proteins. Lyme disease is a bacterial infection transmitted by ticks. Early diagnosis and prompt treatment of Lyme disease reduces complications including arthritis and cardiac involvement. While a urine test is highly desirable for Lyme disease screening, this has been difficult to accomplish because the antigen is present at extremely low concentrations, below the detection limit of clinical immunoassays. N isopropylacrylamide (NIPAm)-acrylic acid (AAc) microparticles were covalently functionalized with amine containing dyes via amidation of carboxylic groups present in the microparticles. The dyes act as affinity baits towards protein analytes in solution. NIPAm/AAc microparticles functionalized with acid black 48 (AB48) mixed with human urine, achieved close to one hundred percent capture and 100 percent extraction yield of the target antigen. In urine, microparticles sequestered and concentrated Lyme disease antigens 100 fold, compared to the absence of microparticles, achieving an immunoassay detection sensitivity of 700 pg/mL in 10 mL urine. Antigen present in a single infected tick could be readily detected following microparticle sequestration. Hydrogel microparticles functionalized with high affinity baits can dramatically increase the sensitivity of urinary antigen tests for infectious diseases such as Lyme disease. These findings justify controlled clinical studies evaluating the sensitivity and precision of Lyme antigen testing in urine. PMID- 21035186 TI - Infant maltreatment-related mortality in Alaska: correcting the count and using birth certificates to predict mortality. PMID- 21035185 TI - Cardiac ischemia-reperfusion regulates sympathetic neuropeptide expression through gp130-dependent and independent mechanisms. AB - Cardiac function is regulated by a balance of sympathetic and parasympathetic transmission. Neuropeptide Y (NPY) and galanin (GAL) released from cardiac sympathetic neurons inhibits parasympathetic transmission in the heart. Sympathetic peptides may contribute to autonomic imbalance, which is characterized by increased sympathetic and decreased parasympathetic transmission and contributes to life threatening cardiovascular pathologies. Several gp130 cytokines are increased in the heart after myocardial infarction (MI), and these cytokines stimulate neuropeptide expression in sympathetic neurons. We used mice whose sympathetic neurons lack the gp130 receptor (gp130(DBH-Cre/lox) mice) to ask if cytokine activation of gp130 regulated neuropeptide expression in cardiac sympathetic nerves after MI. Myocardial infarction decreased NPY mRNA through a gp130 independent mechanism and increased VIP and PACAP mRNA via gp130, while GAL mRNA was unchanged. Immunohistochemistry revealed a gp130-dependent increase in PACAP38 in cells of the stellate ganglion after MI, and PACAP was detected in pre ganglionic fibers of all genotypes and surgical groups. VIP was identified in a few sympathetic nerve fibers in all genotypes and surgical groups. GAL and PACAP38 were not detected in sham hearts, but peptide immunoreactivity was high in the infarct three days after MI. Surprisingly, peptides were abundant in cells that co-labeled with macrophage markers F4/80 and MAC2, but were not detected in sympathetic axons. PACAP protects cardiac myocytes from apoptosis, and GAL stimulates axon regeneration in addition to inhibiting parasympathetic transmission. Thus, these peptides may play an important role in cardiac and neuronal remodeling after ischemia-reperfusion. PMID- 21035188 TI - Use of biomarkers in resident organisms as a tool for environmental monitoring in a cold coastal system, Tierra del Fuego Island. AB - Antioxidant status of Nacella (P) magellanica and Mytilus edulis related with heavy metal in sediment and tissues were analysed in five stations close to Ushuaia city in winter and spring. The principal component analysis produced a two-dimensional pattern of the degree of similarity between sites. The Industrial Urban Contamination Index (IUCI) showed that the Industrial Zone (IZ) and Oil Marine Station (OMS) represent areas with anthropic inputs. Heavy metals have differential association with biomarkers depending on the species. In limpets, digestive gland presented major activities of enzyme defence in winter and gonads have shown higher values of Catalase (CAT) during spring while lipid peroxidation (LPO) presented higher values in IZ. For mussels CAT and LPO increased in spring time. For superoxide dismutase (SOD) peaks have been detected in IZ and NW stations for winter. Differences in biomarker responses due to seasons did not influence the grouping of the sites into references and contaminated groups. PMID- 21035187 TI - Advancing prediction of foster placement disruption using Brief Behavioral Screening. AB - OBJECTIVE: Behavioral difficulties increase the risk that children will experience negative placement disruptions while in foster care. Chamberlain et al. (2006) found that the Parent Daily Report (PDR), a brief measure of parent reported child behaviors, was a strong predictor of negative placement changes over 1 year among children receiving "usual case work" services. This paper sought to replicate and extend original findings regarding the PDR among 359 foster parents participating in a group parent-training intervention. METHODS: Foster parents of children experiencing a recent foster placement, and taking part in the KEEP parenting program, were included in analyses. Foster parents completed 16 weekly PDR calls about the behavior of a foster child in their care during the KEEP intervention and about their stress related to the child's behaviors. Multiple strategies, including latent class analysis of weekly PDR counts and continuous moving averages of PDR counts over shorter time frames, were used to test improvements in prediction of negative placement changes. RESULTS: Consistent with prior findings, children with elevated PDR ratings and children living with non-relative foster parents had significantly higher levels of negative placement disruptions. Prediction improved with decision rules relying upon increased amounts of weekly PDR information, although good prediction was achieved with 3-5 weeks of PDR information. Parent-reported stress associated with behavior did not improve prediction. CONCLUSIONS: This study confirmed the potential utility of the PDR as a predictor of negative placement changes and illustrates how longitudinal PDR information may aid in improving such prediction. Potential applications of the PDR for improving the timing, type, and quantity of services offered to help foster parents prevent placement disruptions are discussed. PMID- 21035189 TI - Tracing cadmium contamination kinetics and pathways in oysters (Crassostrea gigas) by multiple stable Cd isotope spike experiments. AB - Laboratory experiments using stable Cd isotopes ((110)Cd and (112)Cd) were conducted to separately and simultaneously characterize Cd accumulation in different tissues of Pacific oysters (Crassostrea gigas) via the (i) trophic and (ii) direct pathways. For this, we exposed juvenile oysters to (110)Cd-spiked seawater ((110)Cd: 2 MUg l(-1); constant level) and (112)Cd-spiked food (Thalassiossera weissflogii, (112)Cd: 2 MUg l(-1) in 35*10(3) cells/oyster/L) in four experimental treatment groups, each containing 6 oysters, for 21 days with constant trophic feeding. These Cd contamination levels were ~10 times lower than those typically used in experimental accumulation studies. Three oysters per treatment group were dissected every 7 days with separate sampling of the gills, digestive gland and the rest of the body. Metallothioneins were analysed in the digestive gland and gills. Cadmium concentrations and isotope ratios were measured in water (daily) and tissues (weekly) by GF-AAS and ICP-MS. The observed time-dependant evolution in Cd concentrations and (110)Cd/(114)Cd and (112)Cd/(114)Cd isotope ratios clearly revealed the bio-accumulation short-term kinetics and pathways of Cd contamination in the different tissues. Under the experimental conditions, significantly changed isotope ratios in gills and the digestive gland of oysters suggested rapid and efficient contamination by (110)Cd derived from direct exposure followed by internal Cd transfer between organs. Trophic contamination became measurable after 14 days of exposure corresponding to a trophic transfer rate of 1%. Constant metallothionein levels during the experiment suggested that the initially present metallothionein levels were sufficient to deal with the experimental Cd exposure. PMID- 21035191 TI - Mannose-binding lectin complement pathway plays a key role in complement activation by Paracoccidioides brasiliensis. AB - Paracoccidioides brasiliensis (Pb) is a dimorphic fungal pathogen that causes paracoccidioidomycosis, the most severe deep mycosis from South America. Although cell mediated immunity is considered the most efficient protective mechanism against Pb infection, mechanisms of innate immunity are poorly defined. Herein, we investigated the interaction of the complement system with high and low virulence isolates of Pb. We demonstrated that Pb18, a high virulence Pb isolate, when incubated with normal human serum (NHS) induces consumption of hemolytic complement and, when immobilized, promotes binding of C4b, C3b and C5b-C9. Both, low virulence (Pb265) and high virulence (Pb18) isolates consumed C4, C3 and mannose-binding lectin (MBL) of MBL-sufficient, but not of MBL-deficient serum as revealed by deposition of residual C4, C3 and MBL on immune complexes and mannan. However, higher complement components consumption was observed with Pb265, as compared with Pb18. The suggested relationship between low virulence and significant complement activation properties of Pb isolates, was confirmed by the demonstration that virulence attenuation of Pb 18 results in acquisition of the ability to activate complement. Conversely, reactivation of attenuated Pb18, results in loss of the ability to activate complement. Our results demonstrate for the first time that Pb yeasts activate the complement system by the lectin pathway, and there is an inverse correlation between complement activating ability and Pb virulence. These differences could exert an influence on innate immunity and severity of the disease developed by infected hosts. PMID- 21035190 TI - Metal-metal interactions of dietary cadmium, copper and zinc in rainbow trout, Oncorhynchus mykiss. AB - The influence of metal-metal interactions on uptake, accumulation, plasma transport and chronic toxicity of dietary Cu, Cd and Zn in rainbow trout (Oncorhynchus mykiss) was explored. Juvenile rainbow trout were fed diets supplemented with (MUg/g) 500 Cu, 1000 Zn and 500 Cd singly and as a ternary mixture at 2.5% body weight daily ration for 28 days. Complex interactions among the metals dependent on the tissue/organ, metals ratios and duration of exposure were observed. While Zn did not accumulate, whole-body Cd and Cu concentrations increased following linear and saturation patterns, respectively. Early enhanced whole-body Cu accumulation in fish exposed to the metals mixture was correlated with reduced Cd concentration whereas late enhancement of Cd accumulation corresponded with elevated Cd concentration. This suggests early mutual antagonism and late cooperation between Cd and Cu probably due to interactions at temporally variable metal accumulation sites. At the level of uptake, Cd and Cu were either antagonistic or mutually increased the concentrations of each other depending on the duration of exposure and section of the gut. At the level of transport, enhanced Cd accumulation in plasma was closely correlated with reduced concentrations of both Zn and Cu indicating competitive binding to plasma proteins and/or antagonism at uptake sites. Compared to the Cu alone exposure, Cu concentrations were either lower (gills and carcasses) or higher (liver and kidney) in fish exposed to the metals mixture. On the other hand, Cd accumulation was enhanced in livers and carcasses of fish exposed to the mixture compared to those exposed to Cd alone, while Zn stimulated Cu accumulation in gills. Chronic toxicity was demonstrated by elevated malondialdehyde levels in livers and reduced concentrations of Zn and Cu in plasma. Overall, interactions of Cd, Cu and Zn are not always consistent with the isomorphous competitive binding theory. PMID- 21035192 TI - Natural IgM and innate immune collectin SP-D bind to late apoptotic cells and enhance their clearance by alveolar macrophages in vivo. AB - Innate immune collectin surfactant protein D (SP-D) and natural immunoglobulin M (IgM) are two soluble proteins. These opsonic proteins are good candidates for enhancing late apoptotic cell clearance. However, effects of these proteins on late apoptotic cell clearance in the lungs are not clearly established. We have recently shown that SP-D can bind several immunoglobulin isotypes, including IgM. Here we hypothesized that IgM and SP-D bind to late apoptotic cells and enhance their clearance from the lungs. We show that IgM and SP-D bind to late apoptotic secondary necrotic cells, and that IgM and SP-D either co-localize to the same regions or to different regions of late apoptotic Jurkat T cells. Mouse alveolar macrophages internalized late apoptotic cells, in vivo. We induced lung inflammation in mice using LPS and show that airway IgM and SP-D levels and the clearance of late apoptotic cells by alveolar macrophages increases under these conditions. We then coated late apoptotic cells with IgM, SP-D, or both and instilled them into the mouse airways. We found that alveolar macrophages internalize IgM- and SP-D-coated late apoptotic cells more effectively than uncoated late apoptotic cells, in vivo. None of these conditions cause inflammation in the naive lungs. Therefore, these data suggest that both IgM and SP-D effectively opsonize late apoptotic cells and directly enhance their clearance by alveolar macrophages in the lungs. PMID- 21035193 TI - Associations between subtypes of major depressive episodes and substance use disorders. AB - The goal of this study was to examine whether certain subtypes of major depressive episodes (MDEs)-defined by their particular constellations of symptoms were more strongly associated with substance use disorders (SUDs), compared to other subtypes of MDEs. Participants were adults in the National Comorbidity Survey-Replication sample who met DSM criteria for at least one lifetime MDE (n=1829). Diagnostic assessments were conducted using structured interviews. The following MDE subtypes were examined: atypical, psychomotor agitation, psychomotor retardation, melancholic, and suicidal. The results indicated that: (1) suicidal MDEs were associated with increased risk for all SUDs; (2) melancholic MDEs were associated with increased risk for alcohol use disorders; and (3) psychomotor agitation was associated with increased risk for alcohol dependence. These associations did not differ significantly by gender. Adjusting for age, the severity of the MDE, the age of onset of the first MDE, and psychiatric comorbidity did not substantially change the results. Supplemental analyses examining only diagnoses that occurred in the year prior to the assessment demonstrated a similar pattern (with MDEs characterized by psychomotor agitation being associated with drug use disorders as well). Exploratory order of onset analyses indicated that participants with lifetime MDEs and SUDs tended to report an MDE onset prior to the SUD onset, and those who experienced a suicidal MDE at some time in their lives were particularly likely to have had their first MDE prior to developing a SUD. Therefore, risk for lifetime SUDs differs according to the particular set of symptoms experienced during MDEs. PMID- 21035194 TI - Are patients with schizophrenia rational maximizers? Evidence from an ultimatum game study. AB - Schizophrenia is associated with impaired social cognition and community functioning. Social decision-making strategies of healthy controls and patients with schizophrenia were compared by using the ultimatum game (UG). In this game two players have to split a sum of money. The proposer offers a portion to the responder, who decides to either accept or reject the offer. Rejection results in no income to either of the parties. Unfair proposals are frequently rejected by nonclinical individuals, a phenomenon described as altruistic punishment. Patients and controls participated in a series of UG interactions as responders in a computerized test setting. We also tested the effect of the proposer's facial expression on decision-making. Our results indicate that patients with schizophrenia accepted unfair offers at a significantly higher rate than did healthy controls. In contrast, at fair proposals, the acceptance rate was lower in patients compared with controls. At higher offers, the proposer's facial expression (positive/negative) significantly influenced the acceptance rate (positive facial expression increased the likelihood of acceptance) in the control group. This effect was not observed in the patient group. These results suggest that schizophrenia patients are impaired in socioeconomic interactions requiring emotion recognition and decision-making, which may result in unstable behavioral strategies. PMID- 21035195 TI - Delusion-prone individuals: stuck in their ways? AB - Although false memories and confabulation have been linked to both executive dysfunction and greater suggestibility, similar associations with the emergence of delusional thinking remain unexamined. We therefore compared healthy individuals who scored high and low on the Peters Delusional Inventory (PDI: Peters et al., 1999) on measures of set-shifting (the intra-extradimensional set shift task: IED) planning (the Stockings of Cambridge Task: SOC). Additionally, we examined whether high delusion-prone individuals show greater suggestibility on the Gudjonsson Suggestibility Scale (GSS 2: Gudjonsson, 1987). On the IED task, the high group made more pre-extradimensional shift errors than the low PDI group, and this was especially notable for reversal learning. By contrast, no differences emerged on any aspect of the SOC. Finally, and intriguingly, the high PDI group was less likely than the low PDI group to change their responses after receiving suggestive negative feedback. We propose that delusional-style thinking may be underpinned by an orbitofrontal-based reversal learning difficulty affecting the flexibility to adapt responses to changing contingencies and external pressure. PMID- 21035196 TI - Adjuvant activity of chicken interleukin-12 co-administered with infectious bursal disease virus recombinant VP2 antigen in chickens. AB - A recombinant fowlpox virus (rFPV/VP2) expressing infectious bursal diseases virus (IBDV) VP2 gene has been constructed. After purification and identification of rFPV/VP2, the adjuvant activity of the recombinant chicken IL-12 (rchIL-12), synthesized by our previous construct of rFPV/chIL-12, in rFPV/VP2-expressed rVP2 antigen was assessed in one-week-old specific-pathogen free chickens. The results indicated that rchIL-12 alone or rchIL-12 plus mineral oil (MO) co-administered with rVP2 antigen significantly enhanced the production of serum neutralization (SN) antibody against IBDV, compared to those with MO alone. The SN titers in groups receiving rVP2 antigen with MO alone were more inconsistent after vaccination. On the other hand, rchIL-12 significantly stimulated IFN-gamma production in serum and in splenocyte cultured supernatant, suggesting that rchIL 12 alone or plus MO significantly induced a cell-mediated immune response. Finally, bursal lesion protection from very virulent IBDV (vvIBDV) challenge in chickens receiving rVP2 antigen with rchIL-12 alone or plus MO was much more effective than that with MO alone at two weeks after boosting. Taken together, rchIL-12 alone augmented in vivo the induction of a primary and also a secondary SN antibody production and a cell-mediated immunity against IBDV rVP2 antigen, which conferred the enhancement of bursal lesion protective efficacy from vvIBDV challenge. These data indicated that a potential for chIL-12 as immunoadjuvant for chicken vaccine development such as IBDV rVP2 antigen. PMID- 21035197 TI - Humoral and cell-mediated immune responses of old horses following recombinant canarypox virus vaccination and subsequent challenge infection. AB - Equine influenza virus is a leading cause of respiratory disease in the horse population; however, the susceptibility of old horses to EIV infection remains unknown. While advanced age in horses (>20 years) is associated with age-related changes in immune function, there are no specific recommendations regarding the vaccination of older horses even though a well-characterized effect of aging is a reduced antibody response to standard vaccination. Therefore, we evaluated the immunological and physiological response of aged horses to a live non-replicating canarypox-vectored EIV vaccine and subsequent challenge infection. Vaccination of the aged horses induced EIV-specific IgGb and HI antibodies. No specific increase in cell-mediated immune (CMI) response was induced by the vaccine as determined by EIV-specific lymphoproliferation and the detection of EIV-specific IFNgamma(+) CD5(+)T cells, IFNgamma, IL-2, IL-4 and IL-13 mRNA expression. Non-vaccinated aged horses exhibited clinical signs of the disease (coughing, nasal discharge, dyspnea, depression, anorexia) as well as increased rectal temperature and viral shedding following challenge. Concomitant with the febrile episodes, we also observed increased production of pro-inflammatory cytokine mRNA production in vivo using RT-PCR. Naive horses were included in this study for vaccine and challenge controls only. As expected, the canarypox-vectored EIV vaccine stimulated significant CMI and humoral immune responses and provided significant protection against clinical signs of disease and reduced virus shedding in naive horses. Here, we show that aged horses remain susceptible to infection with equine influenza virus despite the presence of circulating antibodies and CMI responses to EIV and vaccination with a canarypox-vectored EIV vaccine provides protection from clinical disease. PMID- 21035198 TI - Use of calcium hydroxylapatite for management of recalcitrant otorrhea due to a patulous eustachian tube. AB - We describe a medically complex 4-year-old child with a history of chronic unilateral myringotomy tube otorrhea and laryngopharyngeal reflux who was diagnosed with a patulous eustachian tube. The diagnosis was confirmed by nasopharyngoscopy, retrieval of food from the affected ear after oral challenges with green dye, and computed tomography. The child was effectively treated with an endoscopic transoral injection of calcium hydroxylapatite (Radiesse Voice) in the lateral pharyngeal wall and torus tubarius. She initially received a test injection with a temporary gel of synthetic polymers (Radiesse Voice Gel) with benefit lasting several months; she subsequently underwent a longer term injection with the hydroxylapatite and tube removal. She had complete resolution of otorrhea for 18 months with no subsequent ear infections or food matter in the ear despite persistent significant gastroesophageal reflux. The patulous eustachian tube is rarely identified in children and, when found, is a challenging condition to manage. Many current surgical treatments involve permanent occlusion of the eustachian tube. Our endoscopic transoral technique is a shorter-term alternative for management of complications related to this anatomic variation, and it allows time for eustachian tube growth. PMID- 21035200 TI - Early expression of zona pellucida proteins under octylphenol exposure in Cichlasoma dimerus (Perciformes, Cichlidae). AB - An increasing number of widely used industrial and agricultural chemicals are being found to cause endocrine disruption. In fishes, xenoestrogens can induce female proteins, and in some cases, the development of testis-ova, demonstrating feminization of males. In this study we analyzed the effect of an acute exposure of adult male Cichlasoma dimerus fish to estradiol (E(2)) and octylphenol (OP). E(2) and OP were injected at 10 and 50 MUg/g body weight doses, respectively. After a single OP dose, liver was processed for RNA extraction at 1, 3, 12, 24, and 72 h. PCR was performed using cDNA and primers for egg coat or zona pellucida proteins (ZP). Genes encoding ZPB and ZPC isoforms were sequenced. E(2)-induced fish were sacrificed at 72 h. Using multiple OP or E(2) injections, blood and surface mucus were sampled on days 0, 3, 6, 9, and 13. On day 13 fish were sacrificed for liver and testis dissection. Histological examination of E(2) and OP-treated fish livers showed cellular disarray and intense cytoplasmatic basophilia within hepatocytes, probably due to increased mRNA synthesis, as well as hypertrophied euchromatic nuclei, and conspicuous nucleoli, indicative of augmented cell activity. An abnormal amount of sperm and immature germ cells within the testis lumen were seen in treated fish, suggesting reproductive impairment. Both plasma and mucus revealed the presence of ZP (and vitellogenin) at day 3 and thereafter with E(2) treatment, using Western and Dot blot techniques; OP effects were delayed in time. These results validate the analysis of mucus by Dot blot as an easy and rapid technique to address endocrine disruption caused by OP. Quantitative gene expression showed induction of liver ZPB and ZPC upon OP injection; muscle, brain, and intestine did not express any ZP. Both ZPs were induced at 1h post injection, but only ZPB expression was statistically significant. At 12h, both ZPs increased significantly, reaching the same levels of E(2)-challenged males after 72 h. Therefore, OP mimicked the action of E(2) with a prompt and strong xenoestrogenic effect, evidenced by the early response through mRNA and protein expression of ZP and the concomitant histological liver and testis alterations. PMID- 21035199 TI - The extra-hypothalamic actions of ghrelin on neuronal function. AB - Ghrelin is a peptide hormone produced and secreted in the stomach. Numerous studies over the past decade demonstrate its importance in food intake, body weight regulation and glucose homeostasis. These effects are driven largely by the high expression of the ghrelin receptor (GHSR1a) in the hypothalamus. However, GHSR1a is also expressed in numerous extra-hypothalamic neuronal populations, suggesting that ghrelin has physiological functions besides those involved in metabolic functions. In this review, I focus on increasing evidence that ghrelin has important roles in extra-hypothalamic functions, including learning and memory, reward and motivation, anxiety and depression, and neuroprotection. Furthermore, I discuss how the recently demonstrated role of ghrelin in promoting survival during periods of caloric restriction could contribute to its inherent neuroprotective and neuromodulatory properties. PMID- 21035201 TI - Physical activity and functional fitness in institutionalized vs. independently living elderly: a comparison of 70-80-year-old city-dwellers. AB - The purpose of the study was to compare the level of energy expenditure due to physical activity (EEPA) and functional fitness (FF) in 59 women and 82 men aged 70-80 years, divided into three groups: permanent residents in assisted-living facilities (ALFs), participants in adult day care centers (DCCs) and older people living independently, members in community senior centers (CSCs). EEPA and FF were analyzed taking into consideration sex differences. The energy expenditure tended to be lower in DCCs and ALFs subjects than in CSCs members, but significant differences were obtained only in women. Women in different living settings differed only in endurance. In men, the differences were clear in most tests (endurance, strength, agility/dynamic balance) except for flexibility. Institutionalization was connected with a significantly lower level of FF and equalization of sex differences. Education seemed to be an important factor influencing the level of FF in men. PMID- 21035202 TI - Is there an advanced aging effect on the ability to mentally represent action? AB - Motor programming theory suggests that an integral component in an effective outcome is an adequate action (mental) representation of the movements; a representation reflected in the ability to use motor imagery. Recent reports show a decline with advanced age (>64 years) using a variety of motor simulation tasks. Here, we examined the possible effects of advanced age on motor imagery ability in the context of estimation of reachability--that is, estimating whether an object is within reach or out of grasp. Thirty young adults (mean age: 20) and 23 older adults (mean age: 77) were instructed to estimate, using motor imagery, whether randomly presented targets in peripersonal (within actual reach) and extrapersonal (beyond reach) space were within or out of reach of their dominant limb while seated. Results indicated that the younger group was significantly more accurate than the older adults, p < 0.001. Whereas both groups made more errors in extrapersonal space, the values were significantly higher for the older group; that is, they overestimated to a greater extent. In summary, these findings add to the general notion that there is a decline in the ability to mentally represent action with advanced age. PMID- 21035203 TI - Thirst in the elderly with and without heart failure. AB - Elderly patients with heart failure (HF) may be troubled by thirst, despite the fact that elderly have an impaired ability to sense thirst. The present study was undertaken to compare the intensity of thirst in patients with and without HF and to evaluate how this symptom relates to the health-related quality of life and indices of the fluid balance. Forty-eight patients (mean age 80 years) admitted to hospital with worsening HF (n = 23) or with other acute illness (n = 25) graded their thirst and estimated their health-related quality of life (HRQoL). Serum sodium was measured and urine samples were assessed for color and electrolyte content. The HF patients reported significantly more intensive thirst (median = 75 mm) compared with those in the control group (median = 25 mm; p < 0.0001). There was no statistically significant relationship between thirst and HRQoL, which was low overall. Serum sodium and urine color did not differ significantly between the groups, but the urine of the HF patients had a lower sodium concentration and osmolality. We conclude that elderly patients with worsening HF have considerably increased thirst and, hence, intense thirst should be regarded as a symptom of HF. PMID- 21035204 TI - Longitudinal changes in clock drawing test (CDT) performance according to dementia subtypes and severity. AB - The CDT requires a patient to draw the face of a clock, insert all the numbers and set the hands for a specified time. This task engages a number of cognitive abilities including verbal understanding, memory, spatially coded knowledge, planning, concentration and visuoconstructive skills. Although CDT has been regarded as a simple and useful screening tool in dementia, little is known about the longitudinal changes in CDT performance and error types, according to dementia subtypes and their severity. MATERIALS AND METHODS: Two hundred thirty five consecutive patients with dementia (Alzheimer disease = AD, n=94, Parkinson's disease with dementia (PDD), n = 119, Vascular dementia = VaD, n = 22) were recruited from the memory clinic at Chungnam University hospital from January 2005 to July 2009. The Korean version of the mini-mental state examination (MMSE-K) and CDT were performed by all participants every 6 months. Scoring of the CDT performance was in accordance with the method of Mano and Wu. Error types of CDT were classified as follows: stimulus-bound response (SBR), conceptual deficit (CD), spatial and/or planning deficit (SPD) and perseveration error (PE). We divided patients into 3 groups by their initial MMSE-K score (severe, MMSE-K <= 17; moderate, 18 <= MMSE-K < 24; mild, 24 <= MMSE-K). Comparisons of CDT scores and error types in the three dementia subtypes and three cognitive groups were conducted. RESULTS: Longitudinal changes on CDT and MMSE-K scores were not different between the three dementia subtypes. From the analysis of CDT error type, the most common error type was SPD in patients with mild to moderate dementia. In contrast, CD error was the most frequent in severe dementia group. The order of error frequency in all subjects from baseline to the last follow-up was as follows: SPD, CD, SBR and PE except CD was the most frequent error type in AD patients after 18 months from baseline. CONCLUSION: Longitudinal analysis of error on CDT may reflect different characteristics of cognitive deterioration according to dementia subtypes and dementia stages. PMID- 21035205 TI - Risk management of developing assistive devices for elderly. AB - This study uses the Delphi method in interviewing experts to identify critical risks in the development of assistive devices. Critical risks included product planning, technology development, production, performance, schedule management, and cost management, comprising 26 risk factors in 6 constructs. This study determined which factors were of high importance, finding a total of 7 market analysis errors. Mind mapping was used to create a knowledge map; and layer expansion was used to understand risk distribution to facilitate risk mitigation and monitoring. Organizational risk strategies could be developed to reduce risk and maintain stability while achieving the objective of developing new products. PMID- 21035206 TI - Physical activity, quality of life and symptoms of depression in community dwelling and institutionalized older adults. AB - This study was aimed to investigate in a sample of Spanish elderly whether measures of physical activity are related to health-related quality of life (HRQoL) and symptoms of depression in community dwelling and institutionalized elderly. The sample was a cohort of 436 elderly (234 women and 202 men, aged 60 98 years) from the North of Spain. 58% were community-dwellers and 42% were institutionalized in senior residences. Participants completed measures of physical activity (Yale Physical Activity Survey, YPAS), HRQoL (Medical Outcomes Study 36-item Short Form Health Survey, SF-36) and symptoms of depression (Geriatric Depression Scale, GDS). All SF-36 domains, except role-emotional, were significantly correlated with the YPAS activity dimension summary index. Physical function, role-physical, general health and vitality correlated with total time activity, and correlations were observed between weekly energy expenditure and physical function, role physical, vitality and mental health. Depressive symptom scores correlated significantly with the YPAS activity dimension summary index and the weekly energy expenditure. Scores for various domains of the SF-36 and for depressive symptoms significantly differed among less and more active individuals of the same sex and institutionalization category. Differences generally reached a higher extent in institutionalized subjects in comparison to community dwellers. In conclusion, physical activity was related to different domains of both the physical and mental components of HRQoL and to decreased depressive symptoms. Results emphasize the positive effects of physical activity in both community-dwelling and institutionalized older adults. PMID- 21035207 TI - Differential impact of heart rate and blood pressure on outcome in patients with heart failure with reduced versus preserved left ventricular ejection fraction. AB - BACKGROUND: In contrast to patients with heart failure (HF) with reduced left ventricular ejection fraction (LVEF; HFREF) the prognostic role of heart rate (HR) and blood pressure (BP) in patients with HF and preserved LVEF (HFPEF) is not well known. The aim of this study was to characterize the relationship between HR and BP and outcomes in HFPEF and to compare it to HFREF. METHODS: The association between HR and BP and outcomes (median follow-up: 38 months) was analyzed in patients with HFREF (LVEF <= 45%; n=6792) and HFPEF (LVEF > 45%; n=988) from the Digitalis Investigator Group trial. RESULTS: Mortality (35% vs. 23%) and HF hospitalization rates (31% vs. 20%; p<0.001 for both) were higher in HFREF compared to HFPEF. In HFREF, higher HR and lower systolic and diastolic BP quartiles were associated with higher mortality and HF hospitalization rates. By contrast, there was no significant association between HR and BP respectively and mortality in HFPEF, and there was no significant association between systolic BP and hospitalization risk in HFPEF either. However, HF hospitalization rates were significantly related to increasing HR and decreasing diastolic BP quartile respectively (4.9, 6.8, 6.8, and 10.5 and 5.5, 8.1, 6.0, and 10.1 respectively events per 1000 person-years) in HFPEF. In HFPEF, there was also evidence of a significant J-shaped relationship between pulse pressure and mortality. CONCLUSIONS: The prognostic value of HR and BP differed substantially between HFREF and HFPEF. These data may provide a foundation for the design of novel interventions in HFPEF patients. PMID- 21035208 TI - Percutaneous recanalization of systemic venous baffle occlusion after atrial switch (Mustard) procedure. PMID- 21035209 TI - The relationship between early left ventricular myocardial alterations and reduced coronary flow reserve in non-insulin-dependent diabetic patients with microvascular angina. AB - AIMS: To evaluate left ventricular (LV) systolic and diastolic myocardial function, and their relation to coronary flow reserve in patients with non insulin-dependent diabetes mellitus (DM) and microvascular angina. METHODS AND RESULTS: We selected a population of 45 normotensive patients with DM (56.3 +/- 8.2 years; 25 males) with LV ejection fraction >50% and microvascular angina (anginal pain, positive imaging stress test and normal coronary angiography). Thirty-five age- and sex-matched healthy controls were also enrolled. All the patients underwent standard echocardiography, Tissue Doppler (TDI), two dimensional strain (2DSE) imaging, and coronary flow reserve (CFR) measurement. LV myocardial early diastolic peak velocities (E(m)) and peak systolic 2DSE were reduced in both interventricular septum (IVS) and LV lateral wall (p<0.01) in DM, as well as CFR (1.89 +/- 0.7 vs 2.55 +/- 0.56, p<0.0001) compared with controls. By multivariate analysis, the independent determinants of E(m) were glycated haemoglobin (beta coefficient=-0.36; p<0.01) and age (beta=-0.46, p<0.001), while global longitudinal strain was predicted by glycated haemoglobin (beta=0.48, P<0.001) and by the duration of the disease (beta=0.38, P<0.005). An independent association between LV global longitudinal strain and CFR (beta coefficient= 0.47, p<0.001) in DM patients was also evidenced. CONCLUSIONS: TDI, 2DSE and CFR are valuable non-invasive and easy-repeatable tools for detecting LV myocardial and coronary function in DM patients with microvascular angina. PMID- 21035210 TI - CA-125 and heart failure: deja vu or "still to be seen". PMID- 21035211 TI - Impact of early abciximab administration on infarct size in patients with ST elevation myocardial infarction. AB - BACKGROUND: Early abciximab administration in patients requiring transportation to undergo primary percutaneous coronary intervention (PPCI) has been reported to improve clinical outcome. We aimed to verify whether early administration leads to reduced infarct size (IS), assessed by delayed-enhancement magnetic resonance imaging (DE-MRI). METHODS: We randomized 110 patients with acute myocardial infarction with symptom-to-diagnosis time <6h to either early (55 patients) or late (55 patients) abciximab administration. DE-MRI was performed at 4 days and 6 months. The primary end point was IS at 6 months. Secondary end points were the rate of ST-segment elevation resolution >= 50% (STR) at 60 min after PPCI, the extent of microvascular obstruction at 4 days, and the change in IS and transmurality at 6 months vs. 4 days. RESULTS: DE-MRI was performed in 103 patients after 4 days, and in 87 at 6 months. The mean IS at 6 months was 13.8 +/ 9.0% in the early vs. 13.0 +/- 9.9% in the Late group (P>0.2). Similarly, microvascular obstruction and the change in IS were not significantly different. The Early group showed a significantly higher STR (94.5% vs. 80.0%, P=0.04) and a larger reduction in infarct transmurality (-9.2 +/- 7.0% vs. -5.9 +/- 6.4%; P=0.03), while a larger reduction in IS was observed only in patients with ECG-to Cath Lab time >60 min. CONCLUSIONS: Early abciximab administration did not lead to a smaller IS at 6-month DE-MRI, and was associated with a significant reduction in IS and transmurality only in patients with longer transportation time, warranting further investigation in this patient subset. PMID- 21035212 TI - The association between glaucoma, vascular function and inflammatory process. PMID- 21035213 TI - Differential effects of bundle branch block morphology in heart failure. PMID- 21035214 TI - Routine upstream versus selective downstream administration of glycoprotein IIb/IIIa inhibitors in patients with non-ST-elevation acute coronary syndromes: a meta-analysis of randomized trials. AB - BACKGROUND: Glycoprotein (GP) IIb/IIIa inhibitors reduce ischemic complications in patients with non-ST-elevation acute coronary syndromes (NSTEACS) who undergo invasive procedures. However the optimal timing of therapy (upstream - at hospital admission in all patients prior to coronary catheterization, or downstream - after coronary angiography selectively in patients prior to percutaneous coronary intervention) is still debated. The aim of this meta analysis was to compare the outcome of NSTEACS patients randomized to routine upstream versus deferred selective downstream GP IIb/IIIa inhibitors. METHODS: We scanned the literature from January 1990 to May 2009 to identify all randomized trials comparing upstream administration of GP IIb/IIIa inhibitors versus its downstream use in invasively managed NSTEACS. RESULTS: In 5 randomized trials a total of 9753 patients were randomized to upstream GP IIb/IIIa inhibitors therapy versus 9716 patients randomized to deferred selective downstream therapy. Upstream therapy was associated with reduced in-hospital or 30-day major adverse ischemic cardiac events (odds ratio=0.90 [95% confidence interval 0.82-0.98], p=0.02). However the risk of major bleeding was significantly higher with upstream therapy (odds ratio=1.35 [1.11-1.63], p=0.002). Combining ischemic and hemorrhagic events in a net clinical end-point showed no significant differences between the two approaches (odds ratio=1.01 [0.92-1.10], p=0.88). CONCLUSIONS: In conclusion early administration of GP IIb/IIIa inhibitors in NSTEACS is associated with significant reduction in ischemic events compared to a selective deferred therapy after coronary angiography. However upstream therapy is also associated with increased bleeding complications. This approach should therefore be reserved for patients at high ischemic and/or low hemorrhagic risk. PMID- 21035215 TI - Factors associated with changes of state of foot conformation and lameness in a flock of sheep. AB - The aim of this research was to investigate transitions between foot conformation, lameness and footrot in sheep. Data came from one lowland flock of approximately 700 ewes studied for 18 months. Multilevel multistate analyses of transitions between good and poor foot conformation states in ewes, and lame and non-lame states in ewes and lambs were conducted. Key results were that the longer sheep had feet in good conformation, the more likely they were to stay in this state; similarly, the longer a ewe was not lame the more likely she was not to become lame. Ewes with poor foot conformation were more likely to become lame (OR: 1.83 (1.24-2.67)) and to be >4 years (OR: 1.50 (1.09-2.05)). Ewes with footrot were less likely to move to good foot conformation (OR: 0.48 (0.31-0.75)) and were more likely to become lame (OR: 3.81 (2.60-5.59)). Ewes lame for >4 days and not treated with parenteral antibacterials had a higher risk of developing (OR: 2.00 (1-3.61)), or remaining in (OR: 0.49 (0.29-0.95)), poor foot conformation compared with ewes never lame. Treatment of ewes lame with footrot with parenteral antibacterials increased the probability of transition from a lame to a non-lame state (OR: 1.46 (1.05-2.02)) and these ewes, even if lame for >4 days, were not more likely to develop poor foot conformation. The risk of a ewe becoming lame increased when at least one of her offspring was lame (OR: 2.03 (1.42-2.92)) and when the prevalence of lameness in the group was >=5% (OR: 1.42 (1.06-1.92)). Lambs were at increased risk of becoming lame when they were male (OR: 1.42 (1.01-2.01)), single (OR: 1.86 (1.34-2.59)) or had a lame dam or sibling (OR: 3.10 (1.81-5.32)). There were no explanatory variables associated with lambs recovering from lameness. We conclude that poor foot conformation in ewes increases the susceptibility of ewes to become lame and that this can arise from untreated footrot. Treatment of ewes lame with footrot with parenteral antibacterials leads to recovery from lameness and prevents or resolves poor foot conformation which then reduces the susceptibility to further lameness with footrot. PMID- 21035216 TI - Correlated time to event data: Modeling repeated clinical mastitis data from dairy cattle in New York State. AB - Mastitis is the most prevalent production disease in dairy herds worldwide and is considered to be the most economically important disease of dairy cattle. Modeling the risk of cows contracting mastitis is therefore of great interest for both targeting prevention programs and evaluating treatment protocols. Clinical mastitis (CM) is a disease of recurrent nature, thus correlation between the subsequent events within one cow may be present. This would violate the assumption behind most statistical time-to-event models. In the case of time to event models, the semi-parametric Cox regression models have become the default tool in modeling the time to an event. Limited methods are currently available to evaluate marginal and random (frailty) effects to account for multiple correlation sources. The objective of this study was to explore the implications of using several Cox or related semi-parametric or parametric models to estimate the hazard for CM in the presence of correlation between events. We evaluated the Andersen-Gill model which uses robust standard errors to account for the correlation, the Conditional Anderson-Gill model that uses stratification to account for event dependence, the Frailty model that introduces a random term to account for unobserved (cow level) heterogeneity, and a related generalized linear mixed model that uses Poisson regression to allow multi-level modeling of time-to-event data. We analyzed data on the occurrence of CM from five dairy farms in New York State. Data were from 8206 cows with 721, 275, 119, and 57 first, second, third, and fourth occurrences of CM, respectively, in the same lactation. The analysis of our sample dataset demonstrated that both cow- and farm-level correlation are present in the case of CM. The Conditional Frailty model was able to model one source of correlation in a random effect and one in a fixed effect. Poisson modeling allowed for simultaneous estimation of within cow correlation and within herd correlation. PMID- 21035217 TI - Heterogeneity in the intergenerational transmission of alcohol consumption: a quantile regression approach. AB - This paper addresses the question of whether the effect of parental drinking on children's later consumption of alcohol - which is frequently found to be of positive sign - exhibits a certain pattern of heterogeneity. In particular, if this effect is more prominent in the upper tail than elsewhere in the distribution of children's alcohol consumption, conventional regression analyses that focus on the mean effect may substantially underrate parental drinking as a risk factor for children's later alcohol abuse. In our empirical application, we address this issue by applying censored quantile regression methods to German survey data. The supposed pattern of heterogeneity is indeed found in the data, at least for daily parental drinking. In addition, the intergenerational transmission of alcohol consumption exhibits gender-specific heterogeneity. PMID- 21035218 TI - Organizing protein-DNA hybrids as nanostructures with programmed functionalities. AB - The structural and functional information encoded in the base sequence of nucleic acids provides a means to organize hybrid protein-DNA nanostructures with pre designed, programmed functionality. This review discusses the activation of enzyme cascades in supramolecular DNA-protein hybrid structures, the bioelectrocatalytic activation of redox enzymes on DNA scaffolds, and the programmed positioning of enzymes on 1D, 2D and 3D DNA nanostructures. These systems provide starting points towards the design of interconnected enzyme networks. Substantial progress in the tailoring of functional protein-DNA nanostructures has been accomplished in recent years, and advances in this field warrant a comprehensive discussion. The application of these systems for the control of biocatalytic transformations, for amplified biosensing, and for the synthesis of metallic nanostructures are addressed, and future prospects for these systems are highlighted. PMID- 21035219 TI - Does the "eyes lead the hand" principle apply to reach-to-grasp movements evoked by unexpected balance perturbations? AB - A fundamental principle that has emerged from studies of natural gaze behavior is that goal-directed arm movements are typically guided by a saccade to the target. In this study, we evaluated a hypothesis that this principle does not apply to rapid reach-to-grasp movements evoked by sudden unexpected balance perturbations. These perturbations involved forward translation of a large (2 * 6 m) motion platform configured to simulate a "real-life" environment. Subjects performed a common "daily-life" visuo-cognitive task (find a telephone and make a call) that required walking to the end of the platform, which was triggered to move as they approached a handrail mounted alongside the travel path. A deception was used to ensure that the perturbation was truly unexpected. Eleven of 18 healthy young adult subjects (age 22-30) reached to grasp or touch the rail in response to the balance perturbation. In support of the hypothesis, none of these arm reactions was guided by concurrent visual fixation of the handrail. Seven of the 11 looked at the rail upon first entering the environment, and hence may have used "stored" central-field information about the handrail location to guide the subsequent arm reaction. However, the other four subjects never looked directly at the rail, indicating a complete reliance on peripheral vision. These findings add to previous evidence of distinctions in the CNS control of volitional and perturbation-evoked arm movements. Future studies will determine whether similar visuo-motor behavior occurs when the available handhold is smaller or when subjects are not engaged in a concurrent visuo-cognitive task. PMID- 21035220 TI - Prediction of foot clearance parameters as a precursor to forecasting the risk of tripping and falling. AB - Tripping and falling is a serious health problem for older citizens due to the high medical costs incurred and the high mortality rates precipitated mostly by hip fractures that do not heal well. Current falls prevention technology encompasses a broad range of interventions; both passive (e.g., safer environments, hip protectors) and active (e.g., sensor-based fall detectors) which attempt to reduce the effects of tripping and falling. However the majority of these interventions minimizes the impact of falls and do not directly reduce the risk of falling. This paper investigates the prediction of gait parameters related to foot-to-ground clearance height during the leg swing phase which have been physically associated with tripping and falling risk in the elderly. The objective is to predict parameters of foot trajectory several walking cycles in advance so that anticipated low foot clearance could be addressed early with more volitional countermeasures, e.g., slowing down or stopping. In this primer study, foot kinematics was recorded with a highly accurate motion capture system for 10 healthy adults (25-32 years) and 11 older adults (65-82 years) with a history of falls who each performed treadmill walking for at least 10 min. Vertical foot displacement during the swing phase has three characteristic inflection points and we used these peak values and their normalized time as the target prediction values. These target variables were paired with features extracted from the corresponding foot acceleration signal (obtained through double differentiation). A generalized regression neural network (GRNN) was used to independently predict the gait variables over a prediction horizon (number of gait cycles ahead) of 1 10 gait cycles. It was found that the GRNN attained 0.32-1.10 cm prediction errors in the peak variables and 2-8% errors in the prediction of normalized peak times, with slightly better accuracies in the healthy group compared to elderly fallers. Prediction accuracy decreased linearly (best fit) at a slow rate with increasing prediction horizon ranging from 0.03 to 0.11 cm per step for peak displacement variables and 0.34 * 10(-3) - 1.81 * 10(-3)% per step for normalized peak time variables. Further time series analysis of the target gait variable revealed high autocorrelations in the faller group indicating the presence of cyclic patterns in elderly walking strategies compared to almost random walking patterns in the healthy group. The results are promising because the technique can be extended to portable sensor-based devices which measure foot accelerations to predict the onset of risky foot clearance, thus leading to a more effective falls prevention technology. PMID- 21035221 TI - Advanced sample preparation for the molecular quantification of Staphylococcus aureus in artificially and naturally contaminated milk. AB - Sample treatment is an essential element when using real-time PCR for quantification of pathogens directly on food samples. This study comparatively evaluated three different principles of sample treatment, i.e. immunomagnetic separation based on phage-derived cell wall binding molecules, matrix solubilization and flotation, in order to establish their suitability for quantifying low numbers of Staphylococcus aureus in milk. All three procedures succeeded to remove S. aureus from the milk matrix, either raw or pasteurized, and, as a result of the concentration of the target cells, minimized the effect of milk associated PCR inhibitors. Sample preparation based on immunomagnetic separation albeit of being user friendly, specific and rapid, failed to allow quantification of low and medium numbers (<10(4)CFU) of S. aureus. In a mastitic milk model cell wall binding domain (CBD)-based target cell extraction revealed results most closely matching those derived from culture-based quantification. Both matrix lysis and flotation allowed quantification of S. aureus at a level of 1-10 cells per ml. Both methods resulted in higher numbers of bacterial cell equivalents (bce) than plating could reveal. Since both methods harvest cells that have been subjected to either mechanical and chemical stresses before quantification, we concluded that the higher bce numbers resulted from a disaggregation of S. aureus clusters initially present in the inoculum. Conclusively, since likely each S. aureus cell of a toxigenic strain contributes to enterotoxin production, molecular quantification could provide an even more realistic impact assessment in outbreak investigations than plating does. PMID- 21035222 TI - Growth potential of Listeria monocytogenes strains in mixed ready-to-eat salads. AB - In this study, a microbiological challenge test in three artificially contaminated retail mixed mayonnaise-based ready-to-eat salads stored at refrigerator temperatures (3 degrees C and 7 degrees C) for 48h was carried out. Shrimp-tomato salad, smoked ham salad and garlic cheese salad were separately contaminated by a suspension of particular Listeria monocytogenes strains. The number of L. monocytogenes, Enterobacteriaceae, staphylococci and total plate count (CFU/g) was determined. Listeria monocytogenes growth potential in the salads was calculated and evaluated. A significant increase in total plate count and L. monocytogenes count throughout storage of all three investigated salads was found. Enterobacteriaceae levels were high at the beginning in all salads but significantly (p<0.05) decreased throughout the experiment depending on the temperature. All investigated L. monocytogenes strains demonstrated growth at both temperatures but expressed different growth potential. Especially garlic cheese salad and smoked ham salad were able to support the growth of Listeria. Shrimp-tomato salad supported growth the least. The growth potential increased with the increasing temperature and exceeded 0.5 log(10) CFU/g in many cases. If the potential for growth is >0.5 log(10) CFU/g, food products can potentially endanger human health. Reference strain (ATCC 7644) showed the least growth potential almost in all cases in comparison with strains isolated from frozen pollock loins and from thermally treated specialty sausage containing preservatives. To eliminate the occurrence of microbiological risks, the shelf life of the studied salads was estimated. PMID- 21035223 TI - Diversity of stress tolerance in Lactobacillus plantarum, Lactobacillus pentosus and Lactobacillus paraplantarum: A multivariate screening study. AB - Sixty-three strains of the taxonomically related species Lactobacillus plantarum subsp. plantarum, L. plantarum subsp. argentoratensis, L. paraplantarum and L. pentosus isolated from sourdoughs and other food and non-food sources and 14 strains of other members of the genus Lactobacillus were screened for their tolerance of acid, alkaline, heat, oxidative, osmotic, detergent and starvation stresses in order to evaluate the diversity of stress response. Most strains of the L. plantarum group were highly tolerant of acid, alkaline and osmotic stress and highly sensitive to detergent stress, while a larger diversity was found for other stress. Multivariate analysis allowed grouping the strains in clusters with similar response patterns. Stress response patterns in the L. plantarum group were similar to those of species of the L. casei/L. paracasei group but clearly different from those of other mesophilic Lactobacillus. No relationship was found between grouping obtained on the basis of stress response patterns and by genotypic fingerprinting (rep-PCR), nor with the taxonomic position or isolation source of the strains. Further experiments with selected strains showed that exponential phase cells were generally but not always more sensitive than stationary phase cells. The ability to grow under stressful conditions showed a slightly better correlation with the ecological conditions prevailing in the isolation niches of the strains. This study will be the basis for further investigations to identify and exploit the basis of diversity in the stress response of lactic acid bacteria. PMID- 21035224 TI - Validation of a stochastic modelling approach for Listeria monocytogenes growth in refrigerated foods. AB - A stochastic modelling approach was developed to describe the distribution of Listeria monocytogenes contamination in foods throughout their shelf life. This model was designed to include the main sources of variability leading to a scattering of natural contaminations observed in food portions: the variability of the initial contamination, the variability of the biological parameters such as cardinal values and growth parameters, the variability of individual cell behaviours, the variability of pH and water activity of food as well as portion size, and the variability of storage temperatures. Simulated distributions of contamination were compared to observed distributions obtained on 5 day-old and 11 day-old cheese curd surfaces artificially contaminated with between 10 and 80 stressed cells and stored at 14 degrees C, to a distribution observed in cold smoked salmon artificially contaminated with approximately 13 stressed cells and stored at 8 degrees C, and to contaminations observed in naturally contaminated batches of smoked salmon processed by 10 manufacturers and stored for 10 days a 4 degrees C and then for 20 days at 8 degrees C. The variability of simulated contaminations was close to that observed for artificially and naturally contaminated foods leading to simulated statistical distributions properly describing the observed distributions. This model seems relevant to take into consideration the natural variability of processes governing the microbial behaviour in foods and is an effective approach to assess, for instance, the probability to exceed a critical threshold during the storage of foods like the limit of 100 CFU/g in the case of L. monocytogenes. PMID- 21035225 TI - Degree of control and delayed intensification of antihyperglycaemic treatment in type 2 diabetes mellitus patients in primary care in Spain. AB - OBJECTIVES: Primary aim: to determine the degree of control of HbA(1c) at the time of treatment intensification (TI) in T2DM patients. Secondary aims: fasting plasma glucose levels; estimation of the elapsed time between HbA(1c) exceeding 7% and TI; antidiabetic combinations used, % patients with good cardiometabolic control (LDL-c<100mg/dL; SBP<130 and DPB<80mmHg and HbA(1c)<7%). RESEARCH DESIGN AND METHODS: one-cohort, multicenter, retrospective, observational study conducted in Spain. Patients diagnosed with T2DM that had switched from monotherapy to combination antidiabetic therapy were evaluated at baseline and after one year of follow-up. RESULTS: a total of 1202 T2DM patients were analyzed. At the time of TI: mean HbA(1c) 8.1%; median time of uncontrolled disease: 2.0 years. After one-year of TI: significant reduction in mean HbA(1c) (8.1% vs.7.0%, p<0.001) and a mean fasting plasma glucose levels reduction (181.1mg/dL vs.144.1mg/dL, p<0.001) was also observed. The percentage of patients under glycemic control (HbA(1c)<7%) increased from 12.2% to 51.6% (p<0.001). Most common antidiabetic combinations: metformin+sulfonylurea (44.1%) and metformin+thiazolidindione (15.9%). CONCLUSIONS: in the population of T2DM patients analyzed, TI was carried out when HbA(1c) values were above those recommended in clinical guidelines (<= 7%), with a delay of two years to address the second step of therapy, despite the consensus recommendation of the ADA/EASD of 3 months. TI was shown to be effective since addition of a second antidiabetic drug led to an average reduction of HbA(1c) of approximately 1%. Metformin was the drug most commonly used as monotherapy being the most frequent combination metformin+sulfonylurea. PMID- 21035226 TI - Assessing treatment barriers in young adults with type 1 diabetes. AB - AIMS: The current study was designed to identify barriers that prevent young adults with DM1 from achieving glycemic control. METHODS: Eighty-three young adult patients with DM1 [age 22.2 +/- 2.8 years (mean +/- SD), duration diabetes 11.3 +/- 5.6 years, HbA1c 8.8 +/- 2.1%] completed a battery of surveys assessing potential barriers to achieving glycemic control. Results of questionnaires were correlated with the patient's most recent HbA1c, and a multiple regression analysis was conducted to determine what barriers were significantly associated with HbA1c levels. RESULTS: Questionnaires that significantly correlated with HbA1c levels included the Conflict Subscale of the Diabetes Responsibility and Conflict Scale (r = .55, p < .01), the Modified Barriers to Adherence Questionnaire (r = .42, p < .01), and the Hospital Anxiety and Depression Scale (r = .31, p < .05). An item analysis of the Modified Barriers to Adherence Scale suggested that patient confidence with carbohydrate counting was most statistically associated with HbA1c [F(3, 80) = 12.95, p < .01, R2=.35]. CONCLUSIONS: Results suggest that despite attempts to educate patients; barriers such as family conflict, psychological issues, and carbohydrate counting remain obstacles impeding glycemic control in young adults with DM1. PMID- 21035228 TI - Pay-for-performance step-by-step: introduction to the MIMIQ model. AB - OBJECTIVES: Pay-for-performance is increasingly used as a system intervention to support quality improvement. Programs are however developed, implemented and evaluated in a heterogeneous way. This is partly due to the broad and disparate theoretical and empirical foundation of P4P practice, which is rapidly evolving. This paper guides the reader through the essential steps which should be taken into consideration when setting up a P4P program. To this end a model called 'Model for Implementing and Monitoring Incentives for Quality' (MIMIQ) is presented. METHODS: Literature review was performed with a search of multiple databases, reference screening and expert consultation. RESULTS: Central to the step-by-step approach is a Plan-Do-Check-Act cycle which incorporates communication, implementation and evaluation as key phases next to program development. In addition, the model explains how the decision making and results of each phase is modified by contextual factors. The model puts emphasis on quality and quality measurement as first items to develop. Only after these are in place, the development of the incentive component can be addressed. CONCLUSIONS: The model presents guidance for designing and implementing P4P programs in a practically structured way. According to future findings the MIMIQ model will continuously evolve as an up to date P4P policy and practice tool. PMID- 21035227 TI - Risk factor associations with clinical distal symmetrical polyneuropathy and various neuropathy screening instruments and protocols in type 1 diabetes. AB - OBJECTIVE: To determine whether DSP and neuropathy-assessment instruments used by non-physicians have similar risk factors. RESEARCH DESIGN AND METHODS: analyses were cross-sectional (n=176). RESULTS: risk factors were similar for DSP and screening devices. CONCLUSIONS: these data support the clinical utility of neuropathy screening devices used by non-physician personnel. PMID- 21035229 TI - The cost-effectiveness of alternative strategies against HBV in Italy. AB - INTRODUCTION: Nowadays, guidelines for the management of HBV infection in Italy, recommend using vaccines but the screening test among non-vaccinated people is useful to detect people that have a clear presence of the virus without symptoms of the disease. Thanks to the screening test, people infected with HBV are administered traditional therapy in order to stop the progression to cirrhosis, liver failure and hepatocellular carcinoma (HCC). These diseases cause the decrease of Qol and cause a high consumption of resources for the health system. The aim of this study is to evaluate the cost-effectiveness of a strategy (test strategy) involving the administration of the screening test to patients at risk and the treatment of the infected according to the protocol therapy. This programme is compared with a strategy (no test strategy) which does not include a screening and treats patients affected by cirrhosis or HCC. METHODS: We created a Markov model following the natural history of the disease and considering the antigen HBeAg to evaluate the cost effectiveness of the test strategy. The analysis was carried out considering a third-party payer perspective. The time horizon considered was 40 cycles of one year. Patients who resulted positive to the test were administered either interferon treatment; or lamivudine or adefovir or entecavir or tenofovir, consistently with the Italian guidelines. Treatments were administered to patients included in the no-test arm after cirrhosis symptoms or HCC. RESULTS: The results of the base case analysis show that patients following the test strategy compared with patients of the no-test approach cost ?17,179/QALY. The Monte Carlo simulation based on a probabilistic sensitivity analysis points out that in 95% of the scenarios assumed, the cost per QALY would be under a hypothetical threshold of ?40,000 which is the amount that international guidelines for decision makers are likely to consider sustainable for a health system. In conclusion, anti-hbv test to all high-risk categories should be highly recommended. PMID- 21035231 TI - Leukocyte accumulation in graft blood vessels during self-limiting acute rejection of rat kidneys. AB - During self-limiting acute rejection preceding chronic vasculopathy, large amounts of leukocytes, predominantly monocytes, interact with the endothelium of renal allografts. We aim to characterize them and to identify targets for functional and interventional studies. Leukocytes were harvested by vascular perfusion from Fischer 344 to Lewis renal allografts or Lewis isografts, followed by flow cytometry, quantitative RT-PCR and genome-wide transcriptional profiling. Leukocyte accumulation peaked in allografts on day 9. The percentage of monocytes expressing MHC class II and CD161 was increased whereas CD4, CD11a, CD43, and CD71 expression remained unchanged. IFN-gamma, IL-1beta, IL-2, IL-10, TNF-alpha, and iNOS mRNA increased in allograft leukocytes but IL-4, IL-6, IL-12, TGF-beta, and tissue factor did not. During acute rejection, 1783 genes were differentially expressed. In conclusion, graft blood leukocytes display a unique state of partial activation during self-limiting rejection. Numerous differentially expressed genes deserve further investigation as potential factors in deciding the fate of the allograft. PMID- 21035230 TI - SLC26A4 expression among autoimmune thyroid tissues. AB - CONTEXT: The PDS gene (SLC26A4) is responsible for Pendred syndrome (PS). Genetic analysis of PDS using Tunisian samples showed evidence for linkage and association with autoimmune thyroid diseases (AITD) emergence. In addition, the PDS gene product, pendrin, was recently identified as a novel autoantigen in Graves' disease (GD) or Hashimoto thyroiditis (HT) patients' sera. OBJECTIVE: The aim of this study was to quantify the PDS gene expression and to evaluate the pendrin in vivo and in vitro immunolocalisation. PATIENTS: A total of 52 thyroid gland tissue samples (22 GD, 11 HT, 5 multinodular goiter (MNG), 3 normal thyroid tissues, 8 papillary thyroid carcinoma (PTC), 1 follicular thyroid carcinoma (FTC) and 2 medullar thyroid carcinoma (MTC)) were explored. METHOD: PDS and pendrin expression levels were determined using quantitative RT-PCR and immuno detection methods. TSH and thyroglobulin (Tg) effects on pendrin expression were investigated by immunofluorescence on primary cell culture from GD thyroid tissues. RESULTS: The relative quantification using PDS transcript level among GD thyroid tissues was increased compared to normal thyroid tissues used as calibrator (mean: 27.17-fold higher than normal thyroid tissues). However, thyroids with HT, carcinoma and MNG showed a decrease expression level (means: 92.05-, 77.68-, 14.3-fold lower than normal thyroid tissues, respectively). These results were confirmed by immunoanalysis. Immunofluorescence results showed an apical and a cytoplasmic pendrin localisation on GD thyroid tissues and a marked pendrin expression reduction on HT thyroid tissues. GD primary cell cultures under TSH and Tg stimulation showed a trafficking improvement of pendrin apical localisation. CONCLUSIONS: Our data point to the presence of a relation between SLC26A4 expression in AITD and thyroid function. PMID- 21035232 TI - A survey of attitudes and perceptions toward oral hygiene among staff at a geriatric nursing home. AB - The aim of this survey was to test the impact of an oral hygiene educational model on attitudes and perceptions toward oral hygiene among nursing home staff members. A pilot questionnaire was distributed to the nursing staff before and after a course on oral hygiene at a geriatric nursing home in Stockholm in 2008. The nursing staff was of the opinion that they had sufficient time to carry out oral hygiene tasks but considered such tasks unpleasant, mainly because of unwillingness and resistance from the residents. These attitudes and perceptions among the nursing staff did not change significantly after oral hygiene education. Future oral hygiene educational models need to be developed with an aim to alter the perceptions and behavior of the nursing home staff. PMID- 21035233 TI - [Investigation of a neonatal case of Enterobacter sakazakii infection associated with the use of powdered infant formula]. AB - INTRODUCTION: The aim of this study was to describe the investigation of a case of meningitis in a neonatal intensive care unit in order to identify the source of infection and the associated risk factors. MATERIAL AND METHODS: An analysis was carried out on the possible risk factors associated with the infection. E. sakazakii was detected in the batch of the powdered infant formula used during the feeding of the neonate and the initial level of contamination of the microorganism was estimated. The strains of E. sakazakii previously isolated in blood and faeces of the infected neonate and those isolated in infant formula were characterised by biotype, pulsotype and antimicrobial susceptibility. RESULTS: E. sakazakii was detected in one opened and two unopened cases of a single batch of powdered infant formula. The E. sakazakii strains isolated in the samples of the product and those isolated in the infected neonate showed the same biochemical, antibiotic susceptibility and PFGE pattern. CONCLUSIONS: The case of meningitis in the neonatal intensive care unit occurred as a result of the use of a powered infant formula contaminated with E. sakazakii at manufacturing level, and an inadequate preparation and storing of the reconstituted product were identified as risk factors. PMID- 21035234 TI - Structure-cytotoxicity relationship in a series of N-phosphorus substituted E,E 3,5-bis(3-pyridinylmethylene)- and E,E-3,5-bis(4-pyridinylmethylene)piperid-4 ones. AB - In order to give further insight on the influence of the aromatic ring nature and the presence of the phosphorus substituent at the piperidone nitrogen atom of E,E 3,5-bis((hetero)arylidene)piperid-4-ones on their antitumor properties, a series of phosphorus substituted E,E-3,5-bis(pyridinylmethylene)piperid-4-ones bearing either 3-pyridine or 4-pyridine rings was obtained. Novel NH-3,5 bis(pyridinylmethylene)piperid-4-ones 1a,b were converted into the corresponding N-phosphorylated derivatives 3a-c, 4a-c differing in the substitution at the phosphorus atom (amidophosphates and amidophosphonates), via direct phosphorylation while N-(omega-phosphorylalkyl)-substituted compounds 8a-c were obtained via aldol-crotonic condensation of preformed N-phosphorylalkyl substituted piperidones with the corresponding pyridinecarboxaldehyde. The cytotoxicity screen has revealed that phosphorylated compounds based on E,E-3,5 bis(4-pyridinylmethylene)piperid-4-one framework displayed higher inhibitory properties toward Caov3, A549, KB 3-1 and KB 8-5 human carcinoma cell lines comparing with their analogues with 3-pyridine rings. Introduction of the phosphorus moiety substantially increased the antitumor properties in the case of E,E-3,5-bis(3-pyridinylmethylene)piperid-4-ones derivatives but this influence less pronounced for more active analogues bearing 4-pyridinyl rings. Most of the compounds tested are potent against multi-drug resistant cell line KB 8-5 affording some guidelines for the search of perspective drug-candidates among phosphorus substituted E,E-3,5-bis((hetero)arylidene)piperid-4-ones. PMID- 21035235 TI - [Management of adults presenting with a thrombocytosis]. PMID- 21035236 TI - 210Pb and 210Po in Finnish cereals. AB - A survey was carried out on the activity concentrations of (210)Pb and (210)Po in cereal grains produced in Finland. The cereal species were wheat (Triticum aestivum), rye (Secale cereale), oats (Avena sativa) and barley (Hordeum vulgare), which account for 90% of the Finnish consumption of cereal products. The survey consisted of 18 flour and 13 unprocessed cereal samples and one hulled grain sample from 22 flour mills. According to the results, the mean (210)Pb/(210)Po concentrations in wheat grains, wheat flour, rye flour, oat grains and barley grains were 0.29, 0.12, 0.29, 0.36 and 0.36 Bq kg(-1), respectively. Combined with the consumption rates of the products, we assess that the mean effective doses from (210)Pb and (210)Po in cereal products for the adult male and female population are 22 and 17 MUSv per year, respectively. PMID- 21035237 TI - Effect of submucosal and intramuscular dexamethasone on postoperative sequelae after third molar surgery: comparative study. AB - We compared the effects of dexamethasone sodium phosphate given submucosally and intramuscularly on postoperative complications after removal of impacted lower third molars in a preliminary randomised prospective clinical trial. Thirty patients, each of whom required removal of a single impacted mandibular third molar under local anaesthesia, were randomly allocated to one of 3 groups of 10 each. The 2 experimental groups were given dexamethasone 4 mg submucosally or intramuscularly, and the control group had no steroid. Facial swelling and maximal interincisal distance were measured by an independent examiner at baseline (preoperatively), and at 1, 3, and 7 days postoperatively. Pain was measured by counting the number of rescue analgesic tablets taken, and from the patients' response to a visual analogue scale (VAS). The mean age of the 16 men and 14 women was 27 years (range 20-48). Both dexamethasone groups showed significant reductions in swelling (p<0.001) and in pain (p<0.05) compared with the control group at all intervals. Submucosal dexamethasone resulted in significantly less trismus than controls on day 1 postoperatively (p=0.04), but there were no significant differences among the groups at the other times. The effects of the two routes of dexamethasone were comparable for all variables. There were no cases of alveolar osteitis or wound infection. Dexamethasone 4 mg given submucosally is an effective way of minimising swelling, trismus, and pain after removal of impacted lower third molars, and is comparable with the intramuscular route. It offers a simple, safe, painless, non-invasive, and cost effective treatment in moderate and severe cases. PMID- 21035238 TI - Single-stage implantation in the atrophic alveolar ridge of the mandible with the Norian skeletal repair system. AB - Dental implants have played a part in rehabilitation of the jaws for more than 40 years, but in some cases they alone are inadequate because of extreme alveolar resorption. Correction may necessitate a two-stage procedure with additional interventions. We have made a preliminary study of the use of the Norian skeletal repair system (SRS), a carbonated calcium phosphate bone cement used to augment the alveolar ridge as a single-stage procedure, with the placement of implants. Ten edentulous patients with insufficient vertical bone in the interforaminal area were treated. After a horizontal osteotomy and crestal mobilisation of the alveolar ridge, implants were placed through the crestal part and fixed in the basal part of the mandible. Norian SRS was used to fill the gap created. The prostheses were inserted 3 months later. Forty implants were inserted. The follow up period was 60 months, and no fractures or dislocations developed. One of the implants was lost and there was one wound dehiscence, but no surgical intervention or revision was necessary. Radiographs showed good consolidation of the bony structure in all cases. We have described a reliable, single-stage procedure for augmentation and implantation in a highly atrophic alveolar crest. A 98% survival is comparable with those of other techniques. Further clinical trials are necessary to replicate these promising results. PMID- 21035239 TI - Assessing seasonal and spatial trends of persistent organic pollutants (POPs) in Indian agricultural regions using PUF disk passive air samplers. AB - The first survey of persistent organic pollutant (POP) concentrations in air across several Indian agricultural regions was conducted in 2006-2007. Passive samplers comprising polyurethane foam (PUF) disks were deployed on a quarterly basis at seven stations in agricultural regions, one urban site and one background site. The project was conducted as a sub-project of the Global Atmospheric Passive Sampling (GAPS) Network. In addition to revealing new information on air concentrations of several organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs), the study has demonstrated the feasibility of conducting regional-scale monitoring for POPs in India using PUF disk samplers. The following analytes were detected with relatively high concentrations in air (mean for 2006 and 2007, pg/m(3)): alpha- and gamma-hexachlorocyclohexane (HCH) (292 and 812, respectively); endosulfan I and II (2770 and 902, respectively); p,p'-DDE and p,p'-DDT (247 and 931, respectively); and for the sum of 48 PCBs, 12,100 (including a site with extremely high air concentrations in 2007) and 972 (when excluding data for this site). PMID- 21035240 TI - Comparison of aromatase inhibitor (letrozole) and immunomodulators (infliximab and etanercept) on the regression of endometriotic implants in a rat model. AB - OBJECTIVE: Novel treatment strategies are needed in the treatment of endometriosis due to limited success rates with the currently available options. As inflammatory and immunological mechanisms have been shown to be involved in the mechanism of the disease, new modalities are likely to emerge. We investigated the effects of infliximab (INF), etanercept (ETA) and letrozole on the regression of experimental endometriosis. STUDY DESIGN: In this experimental randomized trial, endometriosis was induced surgically in 44 adult female Sprague Dawley rats. Establishment of implants was confirmed in 41 animals by a second operation on the 21st day. The rats were then randomly divided into four groups. Group I (n = 10) served as controls. Group II (n = 11) received letrozole (0.18 mg/kg, i.p.), group III (n = 10, i.p.) ETA (2.016 mg/kg, i.p.), and group IV (n = 10) INF (15.12 mg/kg, i.p.) for a second 21-day period. Endometriotic implant size along with peritoneal fluid VEGF level and immunoreactivity were determined before and after the treatment in each group. RESULTS: Endometriotic implant size reduced in all treatment groups. The effect of letrozole and ETA on implant size was similar but was significantly better than INF. Level of VEGF in peritoneal fluid did not change in any treatment group but post-treatment VEGF immunoreactivity was found significantly lower in the letrozole treated group. CONCLUSIONS: Letrozole and ETA caused a regression on the implant size in experimental endometriosis. The only group with decreased VEGF expression was letrozole. PMID- 21035241 TI - Defining the secondary structural requirements of a cocaine-binding aptamer by a thermodynamic and mutation study. AB - Isothermal titration calorimetry (ITC) was used to measure the binding affinity and thermodynamics of a cocaine-binding aptamer as a function of pH and NaCl concentration. Tightest binding was achieved at a pH value of 7.4 and under conditions of no added NaCl. These data indicate that ionic interactions occur in the ligand binding mechanism. ITC was also used to measure the binding thermodynamics of a variety of sequence variants of the cocaine-binding aptamer that analyzed which regions and nucleotides of the aptamer are important for maintaining high-affinity binding. Individually, each of the three stems can be shortened, resulting in a reduced binding affinity. If all three stems are shortened, no binding occurs. If all three of the stems in the aptamer are lengthened by five base pairs ligand affinity increases. Changes in nucleotide identity at the three-way junction all decrease the affinity of the aptamer to cocaine. The greatest decrease in affinity results from changes that disrupt the GA base pairs and the identity of T19. PMID- 21035242 TI - Large catalase based bioelectrode for biosensor application. AB - A large catalase (CAT) (Mr~90kDa), immobilized on multiwalled carbon nanotubes Nafion((r)) (MWCNT-NF) matrix and encapsulated with polyethylenimine (PEI) on glassy carbon electrode (GCE), showed a pair of nearly reversible cyclic voltammetric peaks for Fe((III))/Fe((II)) couple with formal potential of about 0.45V (vs. Ag/AgCl electrode at pH 7.5). PEI significantly reduced the charge transfer resistance and stabilized the bioelectrode through electrostatic interaction. The electron transfer rate constant and surface coverage of the immobilized CAT were 1.05+/-0.2s-1 and 2.1*10-10 mol cm-2, respectively. Studies on electrocatalytic activity and kinetics of GCE/MWCNT-NF/CAT/PEI for hydrogen peroxide (H2O2) showed the apparent Michaelis-Menten constant of 3mM, linear response in the range of 10MUM to 5mM, response time of ~2s for steady state current, and detection limit of ~1MUM. A high operational and storage stability was also demonstrated for the bioelectrode. Hence, the direct electrochemistry of the large catalase and its potential biosensor application have been established through this investigation. PMID- 21035243 TI - Effect of organic amendments on microbial activity in chlorpyrifos contaminated soil. AB - The aim of this research was to study the inhibitory effect of chlorpyrifos (CPF) on soil microbial activity and to evaluate the efficacy of different organic amendments as a biostimulation agent for sustaining the microbial activity and thereby assisting in the remediation of CPF (10 ppm) contaminated soil. Experiments were carried out under controlled conditions (37 degrees C) up to 74 days; CPF was analyzed by GC-ECD while dehydrogenase activity (DHA) was measured as one of the indices of soil microbial activity. Throughout the experiment, there was higher microbial activity in uncontaminated soil (S) as compared to CPF contaminated soil (SP) and overall a considerably high reduction (63.51%) in average DHA was noticed in CPF contaminated soil. Organic amendments enhanced the microbial activity over unamended CPF contaminated soil. The trend of DHA on 24th day was MS (SP + 1% Mushroom Spent) >VC (SP + 1% Vermicompost) >BS (SP + 1% Biogas Slurry) >SP (Soil spiked with 10 ppm CPF) >FM (SP + 1% Farmyard Manure). The enhancement in pesticide dissipation over the unamended soil showed the following trend VC (37%)>MS (24%) >FM (1.9%). In spite of sufficient DHA, BS could not enhance pesticide dissipation over the unamended soil (SP). These results indicate the potential of vermicompost and mushroom spent compost as suitable biostimulation agents to sustain the microbial activity in CPF contaminated soil. PMID- 21035244 TI - Multi-criteria analysis for improving strategic environmental assessment of water programmes. A case study in semi-arid region of Brazil. AB - Multi-criteria analysis (MCA) is a family of decision-making tools that can be used in strategic environmental assessment (SEA) procedures to ensure that environmental, social and economic aspects are integrated into the design of human development strategies and planning, in order to increase the contribution of the environment and natural resources to poverty reduction. The aim of this paper is to highlight the contribution of a particular multi-criteria technique, the analytic hierarchy process (AHP), in two stages of the SEA procedure applied to water programmes in developing countries: the comparison of alternatives and monitoring. This proposal was validated through its application to a case study in Brazilian semi-arid region. The objective was to select and subsequently monitor the most appropriate programme for safe water availability. On the basis of the SEA results, a project was identified and implemented with successful results. In terms of comparisons of alternatives, AHP meets the requirements of human development programme assessment, including the importance of simplicity, a multidisciplinary and flexible approach, and a focus on the beneficiaries' concerns. With respect to monitoring, the study shows that AHP contributes to SEA by identifying the most appropriate indicators, in order to control the impacts of a project. PMID- 21035245 TI - Using biological data from field studies with multiple reference sites as a basis for environmental management: the risks for false positives and false negatives. AB - Field surveys of biological responses can provide valuable information about environmental status and anthropogenic stress. However, it is quite usual for biological variables to differ between sites or change between two periods of time also in the absence of an impact. This means that there is an obvious risk that natural variation will be interpreted as environmental impact, or that relevant effects will be missed due to insufficient statistical power. Furthermore, statistical methods tend to focus on the risks for Type-I error, i.e. false positives. For environmental management, the risk for false negatives is (at least) equally important. The aim of the present study was to investigate how the probabilities for false positives and negatives are affected by experimental set up (number of reference sites and samples per site), decision criteria (statistical method and alpha-level) and effect size. A model was constructed to simulate data from multiple reference sites, a negative control and a positive control. The negative control was taken from the same distribution as the reference sites and the positive control was just outside the normal range. Using the model, the probabilities to get false positives and false negatives were calculated when a conventional statistical test, based on a null hypothesis of no difference, was used along with alternative tests that were based on the normal range of natural variation. Here, it is tested if an investigated site is significantly inside (equivalence test) and significantly outside (interval test) the normal range. Furthermore, it was tested how the risks for false positives and false negatives are affected by changes in alpha level and effect size. The results of the present study show that the strategy that best balances the risks between false positives and false negatives is to use the equivalence test. Besides tests with tabulated p-values, estimates generated using a bootstrap routine were included in the present study. The simulations showed that the probability for management errors was smaller for the bootstrap compared to the traditional test and the interval test. PMID- 21035246 TI - Influence of aerobic and anaerobic conditions on survival of Escherichia coli O157:H7 and Salmonella enterica serovar Typhimurium in Luria-Bertani broth, farm yard manure and slurry. AB - The influence of aerobic and anaerobic conditions on the survival of the enteropathogens Escherichia coli O157:H7 and Salmonella serovar Typhimurium was investigated in microcosms with broth, cattle manure or slurry. These substrates were inoculated with a green fluorescent protein transformed strain of the enteropathogens at 10(7) cells g(-1) dry weight. Survival data was fitted to the Weibull model. The survival curves in aerobic conditions generally showed a concave curvature, while the curvature was convex in anaerobic conditions. The estimated survival times showed that E. coli O157:H7 survived significantly longer under anaerobic than under aerobic conditions. Survival ranged from approximately. 2 weeks for aerobic manure and slurry to more than six months for anaerobic manure at 16 degrees C. On average, in 56.3% of the samplings, the number of recovered E. coli O157:H7 cells by anaerobic incubation of Petri plates was significantly (p < 0.05) higher in comparison with aerobic incubation. Survival of Salmonella serovar Typhimurium was not different between aerobic and anaerobic storage of LB broth or manure as well as between aerobic and anaerobic incubation of Petri dishes. The importance of changes in microbial community and chemical composition of manure and slurry was distinguished for the survival of E. coli O157:H7 in different oxygen conditions. PMID- 21035247 TI - Raman molecular imaging: a novel spectroscopic technique for diagnosis of bladder cancer in urine specimens. AB - BACKGROUND: Raman molecular imaging (RMI) is an optical technology that combines the molecular chemical analysis of Raman spectroscopy with high-definition digital microscopic visualization. This approach permits visualization of the physical architecture and molecular environment of cells in the urine. The Raman spectrum of a cell is a complex product of its chemical bonds. OBJECTIVE: In this work, we studied the possibility of using the Raman spectrum of epithelial cells in voided urine for diagnosing urothelial carcinoma (UC). DESIGN, SETTING, AND PARTICIPANTS: Raman signals were obtained from UC tissue, then from UC touch preps obtained from surgical specimens and studied using the FALCON microscope (ChemImage, Pittsburgh, PA, USA), with a*100 collection objective and green laser illumination (532 nm). Then, urine samples were obtained from 340 patients, including 116 patients without UC, 92 patients with low-grade tumors, and 132 patients with high-grade tumors. Spectra were obtained from an average of five cells per slide. MEASUREMENTS: Raman spectroscopy of cells from bladder cancer (BCa) tissues and patients. RESULTS AND LIMITATIONS: The Raman spectra from UC tissue demonstrate a distinct peak at a 1584 cm(-1) wave shift not present in benign tissues. The height of this peak correlated with the tumor's grade. The signal obtained from epithelial cells correctly diagnosed BCa with sensitivity of 92% (100% of the high-grade tumors), specificity of 91%, and a positive predictive value of 94% and a negative predictive value of 88%. The signal correctly assigned a tumor's grade in 73.9% of the low-grade tumors and 98.5% of the high-grade tumors. RMI for diagnosis of BCa is limited by the need for specialized equipment and training of laboratory personnel. CONCLUSIONS: RMI has the potential to become a powerful diagnostic tool that allows noninvasive, accurate diagnosis of UC. PMID- 21035248 TI - A prospective trial comparing consecutive series of open retropubic and robot assisted laparoscopic radical prostatectomy in a centre with a limited caseload. AB - BACKGROUND: Robot-assisted radical prostatectomy (RALP) is performed worldwide, even in institutions with limited caseloads. However, although the results of large RALP series are available, oncologic and functional outcomes as well as complications from low-caseload centres are lacking. OBJECTIVE: To compare perioperative, oncologic, and functional outcomes from two consecutive series of patients with localised prostate cancer treated by retropubic radical prostatectomy (RRP) or recently established RALP in our hospital, which has a limited caseload. DESIGN, SETTING, AND PARTICIPANTS: One hundred fifty consecutive patients were enrolled. Their data and outcomes were collected and extensively evaluated. INTERVENTION: Seventy-five consecutive patients underwent RRP, and 75 consecutive patients underwent RALP, including all patients of the learning curve. MEASUREMENTS: Patient baseline characteristics, perioperative and postoperative outcomes, and complications were evaluated. End points were oncologic data (positive margins, prostate-specific antigen [PSA]), perioperative complications, urinary continence, and erectile function at 3- and 12-mo follow up. RESULTS AND LIMITATIONS: The preoperative parameters from the two groups were comparable. The positive surgical margin (PSM) rates were 32% for RRP and 16% for RALP (p=0.002). For RRP and RALP, the PSA value was <0.2 ng/ml in 91% and 88% of patients 3 mo postoperatively (p=0.708) and in 87% and 89% of patients 12 mo postoperatively (p=0.36), respectively. Continence rates for RRP and RALP were 83% and 95% at 3-mo follow-up (p=0.003) and 80% and 89% after 12-mo follow-up (p=0.092), respectively. Among patients who were potent without phosphodiesterase type 5 inhibitors (PDE5-I) before RRP and RALP, recovery of erectile function with and without PDE5-Is was achieved in 25% (12 of 49 patients) and 68% (25 of 37 patients) 3 mo postoperatively (p=0.009) and in 26% (12 of 47 patients) and 55% (12 of 22 patients) 12 mo postoperatively (p=0.009), respectively. Minimal follow-up for RRP was 12 mo; median follow-up for the RALP group was 12 mo (range: 3-12). According to the modified Clavien system, major complication rates for RRP and RALP were 28% and 7% (p=0.025), respectively; minor complication rates were 24% and 35% (p=0.744), respectively. CONCLUSIONS: Despite a limited caseload and including the learning curve, RALP offers slightly better results than RRP in terms of PSM, major complications, urinary continence, and erectile function. PMID- 21035249 TI - Robot-assisted radical prostatectomy: is the dust settling? PMID- 21035250 TI - Age-adjusted incidence, mortality, and survival rates of stage-specific renal cell carcinoma in North America: a trend analysis. AB - BACKGROUND: The rising incidence of renal cell carcinoma (RCC) has been largely attributed to the increasing use of imaging procedures. OBJECTIVE: Our aim was to examine stage-specific incidence, mortality, and survival trends of RCC in North America. DESIGN, SETTING, AND PARTICIPANTS: We computed age-adjusted incidence, survival, and mortality rates using the Surveillance Epidemiology and End Results database. Between 1988 and 2006, 43,807 patients with histologically confirmed RCC were included. MEASUREMENTS: We calculated incidence, mortality, and 5-yr survival rates by year. Reported findings were stratified according to disease stage. RESULTS AND LIMITATIONS: Age-adjusted incidence rate of RCC rose from 7.6 per 100,000 person-years in 1988 to 11.7 in 2006 (estimated annual percentage change [EAPC]: +2.39%; p<0.001). Stage-specific age-adjusted incidence rates increased for localized stage: 3.8 in 1988 to 8.2 in 2006 (EAPC: +4.29%; p<0.001) and decreased during the same period for distant stage: 2.1 to 1.6 (EAPC: -0.57%; p=0.01). Stage-specific survival rates improved over time for localized stage but remained stable for regional and distant stages. Mortality rates varied significantly over the study period among localized stage, 1.3 in 1988 to 2.4 in 2006 (EAPC: +3.16%; p<0.001), and distant stage, 1.8 in 1988 to 1.6 in 2006 (EAPC: -0.53%; p=0.045). Better detailed staging information represents a main limitation of the study. CONCLUSIONS: The incidence rates of localized RCC increased rapidly, whereas those of distant RCC declined. Mortality rates significantly increased for localized stage and decreased for distant stage. Innovation in diagnosis and management of RCC remains necessary. PMID- 21035251 TI - Debromination of polybrominated diphenyl ethers by Ni/Fe bimetallic nanoparticles: influencing factors, kinetics, and mechanism. AB - Polybrominated diphenyl ethers have been identified as a new class of organic pollutants with ecological risk due to their toxicity, bioaccumulation, and global distribution. Proper remediation technologies are needed to remove them from the environment. In this paper, Ni/Fe bimetallic nanoparticles were synthesized by chemical deposition and used to degrade decabromodiphenyl ether (BDE209). The characteristics of Ni/Fe nanoparticles were analyzed by transmission electron microscopy, X-ray diffractometry, X-ray photoelectron spectroscopy, and Brunnaer-Emmett-Teller surface area analysis. Ni/Fe bimetallic nanoparticles with diameters in the order of 20-50 nm could effectively degrade BDE209 in the solvent (tetrahydrofuran/water). Influence factors, such as Ni/Fe nanoparticle dosage, initial BDE209 concentration, and Ni loading, on the removal of BDE209 were studied. The results indicated that the degradation of BDE209 followed pseudo-first-order kinetics, and the degradation rate of BDE209 increased with increasing the amount of nano Ni/Fe particles, Ni/Fe ratio, and decreasing the initial concentration of BDE209. Through analyzed the mass balance of the BDE209 removal, degradation was the main process of BDE209 removal. The mechanism of debromination was deduced by analyzing the reaction products using gas chromatography-mass spectrometry, the bromide ion in the solution and varying the solvent conditions. Stepwise hydrogen reduction is the main process of debromination, and the hydrion play an important role in the reaction. Moreover, the experiment of long term performance and leaching of Ni were also carried out to test the stability and durability of Ni/Fe nanoparticles in BDE209 degradation. PMID- 21035252 TI - 2-Chlorophenol consumption and its effect on the nitrifying sludge. AB - The kinetic behavior of a nitrifying sludge exposed to 2-chlorophenol (2-CP) was evaluated in batch culture. The assays were performed using a stabilized nitrifying sludge. In control assays with (mg L(-1)): NH(4)(+)-N (100) and NaHCO(3)(-)-C (250), the substrates were consumed in 8h, the ammonium consumption efficiency was 99% and the NO(3)(-) yield higher than 0.9. When 5mg 2-CP-C L(-1) was added, it was transformed into an unidentified intermediate and the nitrifying efficiency decreased to 10%. Ammonium specific consumption rate diminished 95%, but the NO(3)(-) yield remained higher than 0.9. The biomass previously exposed to 2-CP was newly suspended with NH(4)(+)-N or NO(2)(-)-N in order to evaluate the ammonium and nitrite oxidizing processes. The consumption efficiencies and NO(3)(-) yields were similar to those obtained in control assays. However, the total time required for ammonium and nitrite consumption increased to 120 and 42 h, respectively. Specific consumption rates for NH(4)(+) N and NO(2)(-)-N decreased by 95% and 83% respectively, compared to control assays. Thus, the previous contact to 2-CP had more influence on ammonium oxidizing process than the nitrite oxidizing process. These are the first evidences where a nitrifying sludge exposed to 2-CP are reported. PMID- 21035253 TI - Large pore diameter MCM-41 and its application for lead removal from aqueous media. AB - A room temperature method to create large pore size and pore volume ordered mesoporous silica (MCM-41) is demonstrated. Template removal was achieved with a microwave digestion procedure using a solution of nitric acid and hydrogen peroxide. The silica product exhibited an ordered hexagonal mesostructure, large pore volume (up to 0.99 cm(3)/g), and large pore size (up to 6.74 nm) indicating its potential as a high capacity adsorbent. Surface modification, to enhance the ability of the material to extract potentially toxic metals (PTMs) from water was performed using different amino- and mercapto-functional groups. This paper reports on the extraction of lead ions from aqueous solution to demonstrate the material's significant improvement in adsorption capacity (up to 1000 MUmol g(-1) for lead). Moreover, methods have been developed to regenerate the sorbent allowing 100% recovery of Pb and reuse of the sorbent material in subsequent extractions. The performance of the material was also demonstrated for environmental samples containing relatively high concentrations (ppmv) of mixed metal ions reducing them to lower values (<100 ppbv) indicating that the sorbent may have applicability for environmental remediation of polluted water. PMID- 21035254 TI - A new method for predicting the heats of combustion of polynitro arene, polynitro heteroarene, acyclic and cyclic nitramine, nitrate ester and nitroaliphatic compounds. AB - A new method is presented for estimating the gross and net heats of combustion of important classes of energetic compounds including polynitro arene, polynitro heteroarene, acyclic and cyclic nitramine, nitrate ester and nitroaliphatic compounds. Elemental compositions as well as the presence of some specific polar groups and molecular fragments are important parameters in the new model. The novel method can be easily used for any complex organic compounds with at least one nitro, nitramine or nitrate functional groups by which the predictions of their heats of combustion by the available methods are inaccurate or difficult. The predicted results show that this method gives reliable predictions of heats of combustion with respect to group additivity method and computed values based on atom-type electrotopological state indices for several energetic compounds where the models can be applied. PMID- 21035255 TI - Mineralogical composition of boiler fouling and slagging deposits and their relation to fly ashes: the case of Kardia power plant. AB - Slagging and fouling deposits from a pulverized lignite fired steam generating unit of the Kardia power plant (West Macedonia, Greece) were mineralogically investigated. The structure and cohesion of these deposits varied, usually depending on the level height of the boiler unit where they were formed. Some of the deposits had complex phase composition. The dominant components of the deposits of the burner zone and of the lower and intermediate boiler zones were the amorphous, anhydrite and hematite, while those of the highest levels contained amorphous, and anhydrite. Furthermore, in deposits formed in various other boiler areas gehlenite, anorthite, diopside, quartz, Ca(2)SiO(4), brownmillerite and other crystalline phases were also identified, usually in low amounts or in traces. The major part of the phases constituting the deposits were formed in the boiler, since only a minor part derived from the unreacted minerals present in lignite. Anhydrite was generated from the reaction of SO(2) with CaO formed mainly by the calcination of calcite as well as from dehydration of gypsum contained in lignite, while hematite was produced mainly from the oxidation of pyrite. The calcium-containing silicates formed in the boiler were mainly the products of reactions between CaO and minerals contained in the lignite. PMID- 21035257 TI - Improved removal of estrogenic and pharmaceutical compounds in sewage effluent by full scale granular activated carbon: impact on receiving river water. AB - Sewage effluents are widely recognised as the main source of emerging contaminants, such as endocrine disrupting chemicals (EDCs) and pharmaceuticals in surface waters. A full-scale granular activated carbon (GAC) plant has been installed as an advanced technology for the removal of these contaminants, in a major sewage treatment works (STW) in South-West England as part of the UK National Demonstration Programme for EDCs. This study presented for the first time, an assessment of the impact of a recently commissioned, post-tertiary GAC plant in the removal of emerging contaminants in a working STW. Through regular sampling followed by solid-phase extraction and analysis by liquid chromatography tandem mass spectrometry (LC-MS/MS), a significant reduction in the concentrations of steroidal estrogens was observed (>43-64%). In addition, significant reductions were observed for many of the pharmaceutical compounds such as mebeverine (84-99%), although the reduction was less dramatic for some of the more widely used pharmaceuticals analysed, including carbamazepine and propranolol (17-23%). PMID- 21035256 TI - Bioavailability of methyl parathion adsorbed on clay minerals and iron oxide. AB - Adsorption, desorption and degradation by Pseudomonas putida of methyl parathion (O,O-dimethyl O-p-nitrophenyl phosphorothioate) on montmorillonite, kaolinite and goethite were studied. Metabolic activities of methyl parathion-degrading bacteria P. putida in the presence of minerals were also monitored by microcalorimetry to determine the degradation mechanism of methyl parathion. Montmorillonite presented higher adsorption capacity and affinity for methyl parathion than kaolinite and goethite. The percentage of degradation of methyl parathion adsorbed on minerals by P. putida was in the order of montmorillonite>kaolinite>goethite. The presence of minerals inhibited the exponential growth and the metabolic activity of P. putida. Among the examined minerals, goethite exhibited the greatest inhibitory effect on bacterial activity, while montmorillonite was the least depressing. The biodegradation of adsorbed methyl parathion by P. putida is apparently not controlled by the adsorption affinity of methyl parathion on minerals and may be mainly governed by the activity of the methyl parathion-degrading bacteria. The information obtained in this study is of fundamental significance for the understanding of the behavior of methyl parathion in soil environments. PMID- 21035258 TI - Development of a multi-pathway probabilistic health risk assessment model for swimmers exposed to chloroform in indoor swimming pools. AB - For swimmers, exposure to chloroform, a probable carcinogen, in indoor swimming pools can be through different pathways such as ingestion, dermal absorption, inhalation during swimming, and inhalation during resting. In order to evaluate health risk results from excessive exposure to chloroform, concentrations of chloroform in pool water were first collected and analyzed. Then, a two-layer model is used, which is capable of estimating the concentrations of chloroform in the boundary layer adjacent to the water surface and the concentrations of chloroform in indoor swimming pool air. The use of stratification model is important for estimating the risks for swimmers since they are exposed to these kinds of situations while performing swimming and resting in indoor swimming pools environment. The incremental lifetime cancer risk (ILCR) was then estimated using the multi-pathway exposure model. The results showed that the 95th percentile of ILCRs calculated for male and female swimmers were 2.80 * 10(-4) and 2.47 * 10(-4), respectively. The major exposure routes were found to be inhalation during swimming which contributes to more than 99% of the total health risk. Our study suggested that to protect swimmers from excessive exposure to chloroform, alternative methods or processes of disinfection should be considered for swimming pool managers. PMID- 21035259 TI - Biodegradation of isoproturon using a novel Pseudomonas aeruginosa strain JS-11 as a multi-functional bioinoculant of environmental significance. AB - Biodegradation of phenylurea herbicide isoproturon was studied in soil microcosm bioaugmented with a novel bacterial strain JS-11 isolated from wheat rhizosphere. The molecular characterization based on 16SrDNA sequence homology confirmed its identity as Pseudomonas aeruginosa strain JS-11. The herbicide was completely degraded within 20 days at ambient temperature with the rate constant of 0.08 day(-1), following the first-order rate kinetics. In stationary phase, at a cell density of 6.5 * 10(9) CFU mL(-1), the bacteria produced substantially increased amounts of indole acetic acid (IAA) in the presence of tryptophan as compared with the control. Also, the bacteria exhibited a time-dependent increase in the amount of tri-calcium phosphate solubilization in Pikovskaya's medium. Further screening of the strain JS-11 for auxiliary activities revealed its remarkable capability of producing the siderophores and hydrogen cyanide (HCN), besides antifungal activity against a common phytopathogen Fusarium oxysporum. Thus, the versatile P. aeruginosa strain JS-11 with innate potential for multifarious biological activities is envisaged as a super-bioinoculant for exploitation in the integrated bioremediation, plant growth and disease management (IBPDM) in contaminated agricultural soils. PMID- 21035260 TI - Photocatalytic inactivation of spores of Bacillus anthracis using titania nanomaterials. AB - Studies on photocatalytic inactivation of spores of Bacillus anthracis have been carried out using nanosized titania materials and UVA light or sun light. Results demonstrated pseudo first order behaviour of spore inactivation kinetics. The value of kinetic rate constant increased from 0.4h(-1) to 1.4h(-1) indicating photocatalysis facilitated by addition of nanosized titania. Nanosized titania exhibited superior inactivation kinetics on par with large sized titania. The value of kinetic rate constant increased from 0.02 h(-1) to 0.26 h(-1) on reduction of size from 1000 nm to 16 nm depicting the enhanced rate of inactivation of Bacillus anthracis Sterne spores on the decrease of particle size. PMID- 21035261 TI - Pb(II) and Cd(II) biosorption on Chondracanthus chamissoi (a red alga). AB - Chondracanthus chamissoi is an efficient biosorbent for Pb(II) and Cd(II). The sorption efficiency increases with pH and reaches an optimum around pH 4. Maximum sorption capacity reaches 1.37 mmol P bg(-1) and 0.76 mmol C dg(-1). The biosorbent has a marked preference for Pb(II) over Cd(II), though insufficient for separating these metals by a simple sorption step. The uptake kinetics is controlled by the resistance to intraparticle diffusion with a limited impact of particle size, metal concentration and sorbent dosage. In the present case, grinding the biomass does not improve sorption capacity and uptake kinetics. The sorption of metal ions is probably due to their interaction with carrageenan (one of the main constituents of the biosorbent): sulfonic groups (on the sulfated polysaccharide) have a higher affinity for Pb(II) than for Cd(II) according to HSAB rules. PMID- 21035262 TI - Leaching of metals from fresh and sintered red mud. AB - The disposal of red mud, a solid waste generated during the extraction of alumina from bauxite, is one of the major problems faced by the aluminum industry. Proper disposal followed by its utilization, for example as bricks, can provide a satisfactory solution to this problem. Pollution potential of red mud and its finished product, due to metals leaching out from them under certain environmental conditions, need to be studied. Sintering of red mud was performed in a resistance type vertical tube furnace to simulate the brick-making conditions in lab-scale. Leachability of metals in red mud and the sintered product was evaluated by performing sequential extraction experiments on both. The metals studied were the 'macro metals' iron and aluminum and the 'trace metals' copper and chromium. The total extractabilities of all the metals estimated by the microwave digestion of red mud samples decreased due to sintering. The leachability in sequential extraction of the macro metals iron and aluminum, on the other hand, increased due to sintering in all phases of sequential extraction. However, the effect of sintering on the leachability of the trace metals by sequential extraction was different for copper and chromium in different fractions of sequential extraction. PMID- 21035263 TI - Multiparametric investigation of competitive and noncompetitive sorption characteristics of SMP fractions (carbohydrate and protein) on activated carbon. AB - Sorption characteristics of soluble microbial products (SMPs) as carbohydrate and protein on activated carbon were investigated. Batch experiments were conducted to evaluate the sorption kinetics and the equilibrium conditions. The parameters studied included initial SMP concentration (50-200mg/L), activated carbon dosage (0.25-50 g/L), contact time (0.02-4h), particle size of activated carbon used (5 75 MUm, 75-850 MUm, and 850-1000 MUm), and presence of one or both SMP fractions. The equilibrium sorption of carbohydrate and protein were significantly affected by the presence of the second SMP fraction in the solutions. Adsorption isotherms were expressed by the Langmuir and Freundlich models. The adsorption rates under noncompetitive and competitive conditions were analyzed with kinetics-based Lagergren pseudo-first order and pseudo-second order models; and diffusion-based external diffusion and Weber-Morris intraparticle models. Both SMP fractions were removed effectively, however, sorption of protein was significantly better than that of carbohydrate in all cases. The relatively significant effect of particle size on sorption of protein indicates that protein is most likely adsorbed as a single layer on the carbon surface. For the carbohydrate, the increase in particle size did not decrease the sorption significantly indicating that carbohydrate may be adsorbed in multiple layers or may diffuse into the porous matrix more effectively. PMID- 21035264 TI - Adsorption of acid dyes from aqueous solutions by the ethylenediamine-modified magnetic chitosan nanoparticles. AB - The adsorption characteristics of Acid Orange 7(AO7) and Acid Orange 10 (AO10) from aqueous solutions onto the ethylenediamine-modified magnetic chitosan nanoparticles (EMCN) have been investigated. The EMCN were essentially monodispersed and had a main particle size distribution of 15-40 nm and saturated magnetization of 25.6 emu/g. The adsorption experiments indicated that the maximum adsorption capacity occurred at pH 4.0 for AO7 and pH 3.0 for AO10, respectively. Due to the small diameter and the high surface reactivity, the adsorption equilibrium of AO7 and AO10 onto the EMCN reached very quickly. Equilibrium experiments fitted well with the Langmuir isotherm model, and the maximum adsorption capacity of the EMCN at 298K was determined to be 3.47 mmol/g for AO7 and 2.25 mmol/g for AO10, respectively. Thermodynamic parameters such as enthalpy change (DeltaH degrees ), free energy change (DeltaG degrees ) and entropy change (DeltaS degrees ) were estimated and the results indicated that the adsorption process was spontaneous and exothermic. Furthermore, the EMCN could be regenerated through the desorption of the dyes in NH(4)OH/NH(4)Cl solution (pH 10.0) and could be reused to adsorb the dyes again. PMID- 21035265 TI - Contribution and loading estimation of organochlorine pesticides from rain and canopy throughfall to runoff in an urban environment. AB - Concentrations of OCPs in rain, canopy throughfall, and runoff water were measured in the Beijing metropolitan area during the rainy seasons from 2006 to 2007. This study was conducted to calculate the fluxes of OCPs in rain and canopy throughfall, as well as their contributions to runoff. At urban sites, the contribution of HCB and SigmaHCHs from rainfall accounted for approximately 50% of the mass in runoff. At the site with significant coverage of landscaping trees, the HCB, SigmaHCHs, and SigmaDDTs from the net canopy throughfall accounted for approximately 10% of the mass in the runoff. Based on the data obtained in this study, loadings of OCPs (in MUg) in rain, net canopy throughfall, and runoff water were calculated. The input of OCPs from rain and canopy throughfall water accounted for a significant portion of urban runoff. In cities undergoing rapid urban sprawl, monitoring and control of the transport of OCPs in urban runoff are essential for effective control of environmental hazards in surface water bodies. PMID- 21035266 TI - Reinvestigation of the alkali-metal-induced Ge(111)3 * 1 reconstruction on the basis of boundary structure observations. AB - We have investigated the surface atomic structure of boundary area of Li- and Na induced Ge(111)3 * 1 reconstruction using scanning tunneling microscope. On Li/Ge(111)3 * 1, the 3 * 1 phase was found to be terminated with a single row in the filled-state image and with dimer-like features in the empty-state image. The images of both interior and boundary of the Li/Ge(111)3 * 1 surface are compatible with the honeycomb-chain-channel (HCC) model, which has substrate atoms with double bonds and is well established as the structure of AM/Si(111)3 * 1 surfaces. In contrast, termination with zigzag double rows at the domain boundary edges was observed in the filled-state images of the Na/Ge(111)3 * 1 phase, which is not reconcilable with the HCC structure. The filled-state STM feature of the boundary region of the Na/Ge(111)3 * 1 phase supports a structural model not having Ge = Ge double bonds, which was proposed to interpret its empty state images. The trend of bondings between atoms in the surface layer of the AM induced 3 * 1 reconstruction of Si and Ge is discussed in terms of electronegativity differences. PMID- 21035267 TI - Characterization of the antibody response in birds following infection with wild type and attenuated strains of Eimeria tenella and Eimeria necatrix. AB - Live vaccines containing attenuated parasite strains are increasingly used to control chicken coccidiosis. In this paper antibody responses elicited by infections with wild-type and attenuated strains of Eimeria tenella and Eimeria necatrix were characterized by immunoblotting and ELISA with homologous and heterologous antisera. Few differences between antisera from birds infected with wild and attenuated strains of E. tenella were evident in immunoblots conducted with merozoite antigen preparations from both E. tenella strains, however the reactivity of sera raised in birds infected with the wild-type strain was noticeably more intense. In ELISAs conducted with merozoite antigen preparations, antisera from birds infected with the wild-type strains of E. tenella and E. necatrix consistently produced a significantly higher (P<0.05) antibody response than antisera from birds infected with the attenuated strains. Likewise, avidity ELISAs conducted with the E. tenella strains demonstrated that antibodies in birds infected with the wild-type strain were of significantly higher avidity (P<0.05) than antibodies in birds infected with the attenuated strain. The differences in the antibody responses are probably due to changes in the attenuated strain as a result of selection for precocious development and the less severe tissue damage and inflammation of the intestine resulting from infection with the attenuated strain. PMID- 21035268 TI - Genotyping of Cryptosporidium spp. from free-living wild birds from Brazil. AB - In wild and domestic birds, cryptosporidiosis is often associated with infections by Cryptosporidium galli, Cryptosporidium baileyi and Cryptosporidium meleagridis. In addition to these species, a number of avian Cryptosporidium species yet to be fully characterized are commonly found among exotic and wild avian isolates. The present study aimed to detect and identify samples of Cryptosporidium spp. from free-living wild birds, in order to contribute to the knowledge of the variability of this parasite in the free-living population of Brazil. Stool samples were collected from 242 birds, with the following proportions of individuals: 50 Emberizidae (20.7%), 112 Psittacidae (46.3%), 44 Cardinalidae (18.2%), 12 Turdidae (5.0%), eight Ramphastidae (3.3%), seven Icteridae (2.9%), three Estrilididae (1.2%), two Contigidae (0.8%), two Thraupidae (0.8%) and two Fringilidae (0.8%). Among the 242 fecal samples from wild birds, 16 (6.6%) were positive for the presence of oocysts of Cryptosporidium. Molecular characterization of the 16 samples of Cryptosporidium, were performed with phylogenetic reconstructions employing 292 positions of 18S rDNA. None of the samples of birds was characterized as C. meleagridis. C. galli was identified in one rufous-bellied thrush (Turdus rufiventris), five green winged saltators (Saltator similis), one slate-coloured seedeater (Sporophila schistacea), one goldfinch (Carduelis carduelis) and three saffron finches (Sicalis flaveola). One goldfinch isolate, one buffy-fronted seedeater (Sporophila frontalis), one red-cowled cardinal (Paroaria dominicana) and one other saffron finch (S. flaveola) were identified as C. baileyi. Avian genotype II was found in an isolate from a white-eyed parakeet (Aratinga leucophthalma). Clinical symptoms of cryptosporidiosis in birds have already been described and the number of wild birds which were shedding parasites was high. Therefore, further epidemiological research and disease surveillance of birds in the wild is warranted. PMID- 21035269 TI - Evaluation of a commercial ELISA for the specific detection of antibodies against Besnoitia besnoiti. AB - Bovine besnoitiosis is an economically important disease in cattle caused by the protozoan parasite Besnoitia besnoiti, which occurs endemically in many countries of Africa and Asia and is spreading in Europe. Serological identification of subclinically infected cattle is important to avoid the introduction of infected animals into naive herds. Here we determine the sensitivity and specificity of the PrioCHECK((r)) Besnoitia Ab, a serological test recently introduced into the European market. Analytical specificity was examined using sera from animals experimentally infected with parasites related to B. besnoiti (n=27). Three animals experimentally infected with Neospora caninum or Toxoplasma gondii showed inconclusive reactions in the ELISA (percent positivity relative to the positive control [PP] 10% <= 20%) while all other sera reacted negative (PP<10%). An estimate of the diagnostic specificity was obtained by analysing field sera from bovine herds without besnoitiosis but with abortion problems associated to N. caninum (n=403). The analysis revealed a specificity of 94.3% or 96.8% depending on the applied cut-off (PP 10% or 20%, respectively). Sensitivity was assessed with sera from 110 animals of a herd in Germany where clinical bovine besnoitiosis was first diagnosed in September 2008. A positive serological reference standard was defined regarding sera from animals as reference positive, if these animals had tested positive in at least two of a panel of three other serological tests (two different B. besnoiti immunoblots and one immunofluorescence antibody test) on both of two sampling dates, November 2008 and April 2009. A diagnostic sensitivity of 91.8% or 75.5% was determined for sera collected in November 2008 and a sensitivity of 82.7% or 50% for sera collected in April 2009 (cut-off PP 10% or PP 20%, respectively). The marked drop in sensitivity from November 2008 to April 2009 was predominantly observed in reference-positive cattle without clinical signs. We conclude that PrioCHECK((r)) Besnoitia Ab is a valuable diagnostic tool to detect clinically infected animals. Thus it may be used to support control measures, e.g., for the separation of infected animals from the remaining herd to avoid a further transmission of the infection within the herd. PMID- 21035270 TI - Biological control of cyathostomin (Nematoda: Cyathostominae) with nematophagous fungus Monacrosporium thaumasium in tropical southeastern Brazil. AB - Horses are hosts to a wide variety of helminthes; the most important are the cyathostomin, or small strongyles. The viability of a fungal formulation (pellets) using the nematode-trapping fungus Monacrosporium thaumasium was assessed in biological control of horse cyathostomin. Two groups (fungus-treated and control) consisted of six mares in each group, crossbred (ages of 2.5 and 3.5 years), were placed in pastures of Cynodon sp. naturally infected with horse cyathostomin larvae. In the treated group, each animal received 1g/10 kg body weight (0.2g/10 kg live weight of fungus) of pellets of sodium alginate matrix containing the fungus M. thaumasium orally, twice a week for 6 months. In the control group, animals received (1g/10 kg body weight) of pellets without fungus. The egg count per gram of feces showed difference (p<0.01) in the animals treated with the fungus in relation to the control animals during all months of the experiment. The EPG percentage decrease were 87.5%, 89.7%, 68.3%, 58.7%, 52.5% and 35.2% during June, July, August, September, October and November, respectively. In faecal cultures, there was difference (p<0.05) among animals treated with fungus was found in relation to the control animals during all the experiment month, with percentage reduction of 67.5%, 61.4% and 31.8% in September, October and November, respectively. Difference (p<0.01) was observed in the recovery of infective larvae from pastures that were collected up to 20 cm from the dung pats in pastures in the group treated with the fungus in relation to the control group with a reduction of 60.9% and between 0-20 and 0-40 cm from the faecal pat reduction (p<0.01) was about 56% in the group treated with the fungus M. thaumasium in relation to the control group pasture. There was no difference (p>0.05) between the average weight gains in both animal groups. The treatment of horses with pellets containing the nematophagous fungus M. thaumasium can be effective in controlling cyathostomin in the tropical region of southeastern Brazil. PMID- 21035271 TI - Identification of Tritrichomonas foetus pseudocysts in fresh preputial secretion samples from bulls. AB - Tritrichomonas foetus is a serious veterinary pathogen that causes bovine trichomonosis, a sexually transmitted disease that eventually leads to abortion and infertility. T. foetus has a simple life cycle that consists of only a trophozoitic form. During unfavorable environmental conditions, the trophozoites, which are polar and flagellated, can adopt a spherical shape and internalize their flagella. These rounded organisms are known as pseudocysts. Although it is currently assumed that T. foetus pseudocyst formation is reversible and that it represents a response to stressful conditions, there are no reports showing the presence of this form in vivo. For this reason, the aim of this study was to verify whether T. foetus pseudocysts are encountered in naturally infected bulls. Towards this goal, fresh preputial samples obtained from seven mature bulls that were naturally infected with T. foetus were analyzed using complementary techniques, such as video microscopy, fluorescence microscopy, scanning and transmission electron microscopy. The analyses revealed that approximately 55% of the parasites were in pseudocyst form in each preputial sample, whereas approximately 25% of T. foetus displayed pear-shaped bodies. Previous research demonstrated that in vitro T. foetus pseudocysts are able to divide by a budding process. Here, this division mode was observed in approximately 20% of fresh T. foetus obtained from preputial bovine samples. Thus, this study shows that in infected bulls, pseudocysts are present and occur more frequently than the pear shaped parasites. PMID- 21035272 TI - Discrimination between patients with melancholic depression and healthy controls: comparison between 24-h cortisol profiles, the DST and the Dex/CRH test. AB - Diurnal (24-h) cortisol profiles were compared to DST and Dex/CRH test outcomes with regard to their discriminative power in depressive disorder. With regard to several statistical measures (effect sizes, area under the curve) we found 24-h cortisol profiles to better discriminate between healthy controls and inpatients with the melancholic subtype of depression compared to the DST and Dex/CRH test. In search of a shortened time interval we found the 2-h time window 1000-1200 h of the cortisol profile to be the one with the highest sensitivity (83.3%) and specificity (87.9%). The specificity of the DST was 93.3% and somewhat higher than that of the cortisol profiles and the Dex/CRH test (87.9% and 78.8.%, respectively). However, the sensitivity of the DST was very low (30.8%), in fact similar to that of the Dex/CRH test (30.8%), but much lower than that of the 1000 1200 h interval (83.3%). The assessment of cortisol in plasma is an easy to perform, cost-saving method for the evaluation of the HPA system activity, which may have a series of clinical and scientific implications for the depressive disorder. PMID- 21035273 TI - Effect of freeze-dried leek powder (FDLP) and nitrite level on processing and quality characteristics of fermented sausages. AB - Fermented sausages were produced with 0.84% and 1.68% freeze-dried leek powder (FDLP), providing 75 and 150 mg/kg NaNO(3), respectively, and three levels of added nitrite (0, 75, and 150 mg/kg NaNO(2). A control treatment was also produced with 150 mg/kg NaNO(2). Sausages with FDLP were darker and yellower (p<0.05) than the control. Higher FDLP levels produced less red, yellower and darker sausages (p<0.05). Lower FDLP levels resulted in higher (p<0.05) sensory scores for external appearance, flavour and overall acceptability. No differences were found among the treatments with FDLP plus 75 or 150 ppm NaNO(2) in TBA value, lightness, redness (cross section), redness stability, yellowness, texture parameters and sensory firmness, flavour and overall acceptability. The use of 0.84% FDLP and 75 ppm NaNO2 is considered more appropriate for the production of fermented sausages, as it results in a 50% reduction in added nitrite. PMID- 21035274 TI - Cigarette smoking in young adults: the influence of the HTR2A T102C polymorphism and punishment sensitivity. AB - BACKGROUND: The C allele of a common polymorphism of the serotonin 2A receptor (HTR2A) gene, T102C, results in reduced synthesis of 5-HT2A receptors and has been associated with current smoking status in adults. The -1438A/G polymorphism, located in the regulatory region of this gene, is in linkage disequilibrium with T102C, and the A allele is associated with increased promoter activity and with smoking in adult males. We investigated the contributions of the HTR2A gene, chronic psychological stress, and impulsivity to the prediction of cigarette smoking status and dependence in young adults. METHODS: T102C and -1438A/G genotyping was conducted on 132 healthy Caucasian young adults (47 smokers) who completed self-report measures of chronic stress, depressive symptoms, impulsive personality and cigarette use. RESULTS: A logistic regression analysis of current cigarette smoker user status, after adjusting for gender, depressive symptom severity and chronic stress, indicated that the T102C TT genotype relative to the CC genotype (OR=7.53), and lower punishment sensitivity (OR=0.91) were each significant predictive risk factors. However, for number of cigarettes smoked, only lower punishment sensitivity was a significant predictor (OR=0.81). CONCLUSIONS: These data indicate the importance of the T102C polymorphism to tobacco use but not number of cigarettes smoked for Caucasian young adults. Future studies should examine whether this is explained by effects of nicotine on the serotonin system. Lower punishment sensitivity increased risk of both smoking and of greater consumption, perhaps via a reduced sensitivity to cigarette health warnings and negative physiological effects. PMID- 21035275 TI - Abnormal visual experiences in individuals with histories of hallucinogen use: a Web-based questionnaire. AB - Despite longstanding reports of prolonged or reoccurring perceptual changes in a subset of hallucinogen users, very little is known about Hallucinogen Persisting Perception Disorder and related visual abnormalities in hallucinogen users. We used an online questionnaire to document the symptoms and relationship to drug use of unusual visual phenomena in hallucinogen users. 16,192 individuals viewed the information sheet and 2679 were included in the study. Of these, 224 reported having unrelated diagnoses associated with unusual visual experiences and were excluded from main analyses. Most (60.6%) of the remaining 2455 participants reported having experienced drug-free visual experiences that resembled hallucinogen effects. Probability of experiencing constant or near-constant symptoms was predicted by greater past exposure to specific hallucinogens, including lysergic acid diethylamide (LSD). Although symptoms were common, few (104, or 4.2% of the sample) found them distressing or impairing enough to consider seeking treatment. Visual changes in hallucinogen users may be more common than previously suspected and are worthy of further study. PMID- 21035277 TI - Different Mycobacterium avium subsp. paratuberculosis MIRU-VNTR patterns coexist within cattle herds. AB - A better understanding of the biodiversity of Mycobacterium avium subsp. paratuberculosis (MAP) offers more insight in the epidemiology of paratuberculosis and therefore may contribute to the control of the disease. The aim of this study was to investigate the genetic diversity in bovine MAP isolates using PCR-based methods detecting genetic elements called Variable-Number Tandem Repeats (VNTRs) and Mycobacterial Interspersed Repetitive Units (MIRUs) to determine if multiple MAP strains can coexist on farms with endemic MAP infection. For 52 temporal isolates originating from infected cattle from 32 commercial dairy herds with known trading history, MIRU-VNTR analysis was applied at 10 loci of which six showed variation. Within the group of 52 isolates, 17 different MIRU-VNTR patterns were detected. One MIRU-VNTR pattern was found in 29 isolates, one pattern in four isolates, one pattern in three isolates, two times one MIRU-VNTR pattern was found occurring in two isolates, and 12 patterns were found only once. Eleven herds provided multiple isolates. In five herds a single MIRU-VNTR pattern was detected among multiple isolates whereas in six herds more than one pattern was found. This study confirms that between dairy farms as well as within dairy farms, infected animals shed MAP with different MIRU-VNTR patterns. Analysis of trading history and age within herds indicated that cows born within the same birth cohort can be infected with MAP strains exhibiting variations in the number of MIRU-VNTR repeats. These data indicate that such multiple genotypes of MAP can coexist within one herd. PMID- 21035276 TI - The role of Alcoholics Anonymous in mobilizing adaptive social network changes: a prospective lagged mediational analysis. AB - OBJECTIVE: Many individuals entering treatment are involved in social networks and activities that heighten relapse risk. Consequently, treatment programs facilitate engagement in social recovery resources, such as Alcoholics Anonymous (AA), to provide a low risk network. While it is assumed that AA works partially through this social mechanism, research has been limited in rigor and scope. This study used lagged mediational methods to examine changes in pro-abstinent and pro drinking network ties and activities. METHOD: Adults (N=1726) participating in a randomized controlled trial of alcohol use disorder treatment were assessed at intake, and 3, 9, and 15 months. Generalized linear modeling (Generalized linear modeling) tested whether changes in pro-abstinent and pro-drinking network ties and drinking and abstinent activities helped to explain AA's effects. RESULTS: Greater AA attendance facilitated substantial decreases in pro-drinking social ties and significant, but less substantial increases in pro-abstinent ties. Also, AA attendance reduced engagement in drinking-related activities and increased engagement in abstinent activities. Lagged mediational analyses revealed that it was through reductions in pro-drinking network ties and, to a lesser degree, increases in pro-abstinent ties that AA exerted its salutary effect on abstinence, and to a lesser extent, on drinking intensity. CONCLUSIONS: AA appears to facilitate recovery by mobilizing adaptive changes in the social networks of individuals exhibiting a broad range of impairment. Specifically by reducing involvement with pro-drinking ties and increasing involvement with pro abstinent ties. These changes may aid recovery by decreasing exposure to alcohol related cues thereby reducing craving, while simultaneously increasing rewarding social relationships. PMID- 21035278 TI - A comparative study of the interaction of Bartonella henselae strains with human endothelial cells. AB - Bartonella henselae can cause a wide range of clinical outcomes and may lead to severe disease, especially in patients with acquired immunodeficiency syndrome. It is well-known that B. henselae-induced cell proliferation is mediated by anti apoptotic activity; however, the detailed mechanism is still unclear. In this study, the cellular responses of endothelial cells after infection with four B. henselae strains were compared and protein candidates that may be involved in the interaction between cells and bacteria were determined. The Houston-1 strain elicited the fastest response in terms of stimulating endothelial cell proliferation, and the JK-40 strain had the strongest ability to induce cell proliferation. By Western blot analysis, it was demonstrated that B. henselae induced cell proliferation involved the mitochondria intrinsic apoptotic pathway. In addition, the adhesion abilities of the U-4 and JK-40 strains were much greater than those of the Houston-1 and JK-47 strains; however, the ability of Houston-1 to invade host cells was high. By two-dimensional gel electrophoresis analysis, it was found that succinyl-CoA synthetase subunit beta, phage-related protein, and ATP synthase subunit alpha might be involved in the invasion process. The expression of superoxide dismutase [Cu-Zn] precursor increased with infection time for all four strains but was significantly higher in the Houston-1 strain, which may increase the competitive advantage of Houston-1 in terms of survival in host cells and render it successful in invading host cells and stimulating cell proliferation. Our data suggest that the interaction of B. henselae and endothelial cells differed between strains, and the results indicated possible candidate proteins that may play a role in the pathogenesis of B. henselae infection. PMID- 21035279 TI - Bovine herpesvirus 4 immediate early 2 (Rta) gene is an essential gene and is duplicated in bovine herpesvirus 4 isolate U. AB - The ORF50/Rta gene has been shown to be an essential gene for many gammaherpesviruses. Although the BoHV-4 ORF50/Rta homolog, immediate early gene 2 (IE2), has been shown to activate several BoHV-4 early and late promoters in cotransfection assays, there is no direct proof of its indispensability for progression of the virus to the lytic replication cycle in the context of the viral genome. In the present communication, replication defective BoHV-4-V.test IE2 mutants were efficiently rescued, with respect to production of infectious virus and DNA replication, upon the expression of BoHV-4 ORF50/Rta in trans. Surprisingly, in the course of our studies, we discovered that the IE2 gene is duplicated in the genome of BoHV-4-U. PMID- 21035280 TI - Interaction of zearalenone and soybean isoflavone on the development of reproductive organs, reproductive hormones and estrogen receptor expression in prepubertal gilts. AB - The aim of the present study was to investigate the interactive effect of zearalenone (ZEA) and soybean isoflavone (ISO) on the development of reproductive organs, reproductive hormones and estrogen receptor expression in prepubertal gilts. Ninety 75-day-old female pigs (Duroc * Landrace * Yorkshire, 26.50 +/- 0.60 kg) were randomly allocated to nine diet treatments during the 21 day study. The experiment employed a 3 * 3 factorial design using a non-soybean meal diet with addition of 0, 0.5 or 2.0mg/kg ZEA and 0, 300 or 600 mg/kg ISO. The results indicated that diets supplemented with 600 mg/kg ISO could reduce the increased weight of the reproductive organs induced by ZEA at 2mg/kg (P<0.05) while feed containing ISO and 0.5mg/kg ZEA increased the weight of the reproductive organs compared with pigs fed diets with 0.5mg/kg ZEA alone. Diets with ISO at 600 mg/kg reduced the large width of vulvas induced by diets with 2mg/kg ZEA (P<0.05). Simultaneous provision of ZEA and ISO to prepubertal gilts increased the level of E2 at days 7 and 14, but decreased it at day 21 (P<0.05). Pigs simultaneously fed 2mg/kg ZEA and 600 mg/kg ISO had the highest level of FSH (P<0.05). There was a significant interaction (P<0.05) between ZEA and ISO supplementation on the level of LH, and pigs offered diets with 2mg/kg ZEA and 600 mg/kg ISO had the lowest level of LH on days 14 and 21. Animals supplemented simultaneously with ZEA and ISO showed higher ERalpha/ERbeta mRNA expression compared to those offered diets containing 0.5mg/kg ZEA alone or basal diets. However, this simultaneous supplementation resulted in a lower level of ERalpha/ERbeta mRNA expression compared to offering diets with 2mg/kg ZEA alone. It appears that ISO can counteract the estrogenic influence of a high dosage of ZEA (2mg/kg). This affect might be attributed to competitive binding with estrogen receptors, thereby weakening the estrogenic effect of ZEA. Meanwhile, interactions between ZEA and ISO may interfere with the functioning of E2, FSH and LH in prepubertal gilts. PMID- 21035281 TI - Hormonal influences in multiple sclerosis: new therapeutic benefits for steroids. AB - Multiple sclerosis (MS) is one of the most common neurological disorders. It affects mainly women. This autoimmune disease of the central nervous system (CNS) is characterized by intermittent or chronic damage to the myelin sheaths (demyelination), focal inflammation and axonal degeneration. During the early relapsing/remitting stages of MS, myelin can regenerate, but as the disease progresses the remyelination of axons becomes insufficient, leading to impaired axon conduction, neurodegeneration and the worsening of symptoms. The present pharmacological treatment of MS is limited to the administration of immunomodulatory and anti-inflammatory drugs, which are only palliative and do not significantly slow progress of the disease. What are needed are agents that target different cell types in the CNS to protect axonal networks and stimulate the endogenous capacity of myelin repair. Estrogens and progestins may be the basis for such a new therapeutic approach. Although clinical observations provide only indirect or insufficient evidence for an influence of sex steroids on the progress of MS, experimental studies have shown that estrogens and progestins exert multiple beneficial effects in experimental autoimmune encephalomyelitis (EAE), a widely used MS disease model. Moreover, both types of hormones have been shown to promote the viability of neurons and the formation of myelin. These promising experimental results should encourage the launch of prospective clinical studies to clarify the influence of hormones on the course of MS and the effect of hormone treatments, in particular those presently used in contraception and hormone replacement therapy (HRT). PMID- 21035282 TI - Diagnostic performance of transvaginal gray-scale ultrasound for specific diagnosis of benign ovarian cysts in relation to menopausal status. AB - In this study we aimed to assess the diagnostic accuracy of transvaginal ultrasound for assigning a specific diagnosis to benign adnexal masses in pre- and postmenopausal women. The study comprised 2146 adnexal masses in 1980 women. 1420 women were premenopausal and 560 were postmenopausal. Specific diagnosis of presumed histology of the lesion using gray-scale ultrasound findings was provided based on examiner's impression. Definitive diagnosis was obtained in all cases. Sensitivity and specificity for each diagnosis were calculated in both pre and postmenopausal women. Specificity for malignant tumors was significantly higher in premenopausal women (p<0.001). Sensitivity for endometrioma (p<0.05) and hemorrhagic cyst (p<0.01) was significantly higher in premenopausal women. There was a trend for a higher sensitivity for serous cyst in postmenopausal women (p=0.09). We conclude that the diagnostic performance of transvaginal gray scale ultrasound for specific diagnosis of adnexal masses based on examiner's impression is different in premenopausal and postmenopausal women. PMID- 21035283 TI - Women in French medicine and psychiatry in the belle epoque: a feminist cause? AB - In France, women's relatively early admission to the medical profession (1868) and to psychiatry (1903) co-existed with a conservative gender discourse concerning women's presumed and pre-determined domestic role. The two women doctors featured in this article (both interns in psychiatry), Madeleine Pelletier and Constance Pascal, illustrate many of the constraints operating on exceptional women in the professions, but each had the capacity to exploit the opportunities for career development in the belle epoque, and to negotiate the pitfalls of gender construction. PMID- 21035285 TI - Caveats against an improper use of hair testing to support the diagnosis of chronic excessive alcohol consumption, following the "Consensus" of the Society of Hair Testing 2009 [Forensic Science International 196 (2010) 2]. PMID- 21035284 TI - A novel microassay for measuring blood alcohol concentration using a disposable biosensor strip. AB - A novel disposable amperometric biosensor strip for determination of blood alcohol concentration (BAC) with small volume of sample has been constructed using screen-printed electrodes (SPE), nanocomposite film and alcohol dehydrogenase (ADH). Firstly, the GNPs-MWCNT-Nafion nanocomposite film modified on a working electrode was made of Nafion-117, multi-wall carbon nanotubes (MWCNT) and gold nanoparticles (GNPs). After that Meldola's blue (MB) acted as an electron transfer mediator and the mixed solution of ADH, nicotinamide adenine dinucleotide (NAD(+)) were modified in order on the nanocomposite film. At last, a hydrophilic membrane which had an eyehole in center was placed at the outermost of the working area to make a reaction tank of 5 MUL, then the hydrophilic membrane/ADH-NAD(+)/GNPs-MWCNT-MB-Nafion/SPE was prepared. The detection of BAC can be accomplished with 5 MUL of blood sample obtained precisely by siphonage. Optimum conditions of the biosensor were experimentally determined by varying several important parameters: working potential, solution pH value, environmental temperature and interferences. Experimental results indicated that the biosensor possessed a good accuracy and stability, the linear response range was 2.0 * 10( 4) to 25 * 10(-3)mol/L and the detection limit of the biosensor was 5.0 * 10( 5)mol/L (S/N=3). In the measurement of blood samples, the proposed biosensor had excellent detection performance for measuring BAC and showed a good correlation with gas chromatography. The prepared biosensor strip can be valid for the analysis of BAC. PMID- 21035287 TI - Thymidylate synthase expression as a predictor of clinical response to 5 fluorouracil-based chemoradiotherapy in patients with maxillary sinus squamous cell carcinoma. AB - OBJECTIVE: The aim of this study was to evaluate the immunohistochemical TS expression in patients with maxillary sinus SCC. METHODS: The value of immunohistochemical TS expression as a predictive indicator for 5-FU efficacy was retrospectively examined in 47 patients with maxillary sinus SCC. RESULTS: Of the 47 patients, 29 (62%) showed complete response for 5-FU based chemoradiotherapy. Seventeen of 19 (89%) TS low cases showed a complete response, whereas 12 of 28 (43%) TS high cases showed complete response for 5-FU based chemoradiotherapy. Low TS patients had significantly better response rates compared with high TS patients. CONCLUSION: These findings suggest that TS expression affects the chemotherapeutic effect of 5-FU in patients with maxillary sinus SCC and the assessment of TS expression level might be useful both in the management and in the treatment of maxillary sinus SCC. PMID- 21035286 TI - Relevance and characteristics of gastroesophageal reflux in adult patients with otitis media with effusion. AB - OBJECTIVE: To investigate relevance and characteristics of gastroesophageal reflux (GER) in adult patients with otitis media with effusion (OME) of unknown etiology who attended private clinics. MATERIALS AND METHODS: A total of 186 adults with OME of unknown etiology (OME group) and 156 adults without OME (control group) were asked to answer a questionnaire specific for the diagnosis of GER disease. Pepsinogen (PG) levels in the middle-ear effusions (MEEs) of the OME group were measured using a chemiluminescence enzyme immunoassay kit. Distributions of PG concentrations by age or body mass index (BMI) in the OME group were analyzed. Patients with high PG levels received proton pump inhibitors (PPIs) and their responses were evaluated. RESULTS: Symptoms of GER were reported by significantly more patients in the OME group than in the control group (43.0% vs. 12.8%). Patients with GER symptoms tended to have higher MEE PG concentrations than those without symptoms. PG levels did not show a significant difference by age. However, high PG levels were less found in patients over 60 years old with high BMI >25. This tendency was not observed in patients under 60 years old. PG levels decreased in seven out of ten patients with high PG concentrations after PPI therapy, corresponding with palliation of GER-related symptoms. Two patients had high MEE bilirubin concentration, and OME resolved in these patients after instruction about lifestyle factors related to GER, including sleeping position. CONCLUSIONS: GER symptoms were more prevalent than expected in patients with OME of unknown etiology. BMI might affect GER-related OME, especially in elderly patients. Instruction about lifestyle factors related to GER, especially in patients who do not respond to PPI therapy, may be effective for patients with intractable OME. PMID- 21035288 TI - A case of hemodialysis-associated amyloidosis localized to the external auditory canal. AB - Amyloidosis of the external auditory canal is extremely rare. Only 12 cases, including the present case, have been reported, and this is the second reported case attributed to dialysis. This case involved a 56-year-old man who had been on dialysis for 12years. A tumor was visible in the right external auditory canal and caused pain. The tumor was resected at another hospital, but subsequently recurred with rapid increase in size due to infection. We therefore performed further resection at our hospital. We report our experiences herein, together with a discussion of the literature. PMID- 21035289 TI - Results of revision tympanoplasty for chronic non-cholesteatomatous otitis media. AB - OBJECTIVE: To evaluate the success rate for revision tympanoplasty using different graft materials, to compare results of primary and re-tympanoplasty using the same technique and to analyse the effect of potential influencing factors on closure of tympanic membrane (TM) and hearing outcome. METHODS: Study included all patients, who underwent tympanoplasty (n=617) and re-tympanoplasty (n=94) for chronic otitis media without cholesteatoma in the period between September 1998 and 2007. The data of all patients on preoperative disease, perforation size and localization, middle ear status, surgical approach, graft material, adjunctive procedures, pre- and postoperative morphological (otomicroscopy) and functional (hearing examination evaluating pure-tone audiogram) results were analyzed. All operations were performed using an underlay technique and either the retroauricular or transcanal approach. The temporal fascia, perichondrium or cartilage-perichondrium composite grafts were used for the reconstruction of TM. Ossiculoplasty was performed as needed. The interrelation between multiple pre-operative parameters and post-operative morphological (closure of the perforation) and functional (hearing level) outcomes was analysed. RESULTS: Successful closure rates of the TM perforation were 93.6% and 90.2% of the patients in the primary and revision tympanoplasty groups, respectively. Graft take rate and hearing results did not depend on graft material. Structural changes were found more frequently in the re-tympanoplasty group (63.4% comparing to 29.5% of primary cases). Ossiculoplasty was performed more often in revision cases (24.4% comparing to 11.4% of primary cases). Successful hearing (ABG within 20dB) for primary tympanoplasties was achieved in 81.1%, and for retympanoplasty - in 69.5% of the cases. (p<0.01). There were no interrelation between any estimated parameters and the graft take rate for either primary or revision tympanoplasty. CONCLUSIONS: There is no evidence of increased risk of graft failure in re-tympanoplasty cases when compared to primary tympanoplasty operations. Hearing results depend on structural changes in the middle ear (ossicular abnormalities and tympanoscerosis) which in revision cases are found more often. No differences were found between fascia, perichondrum or cartilage-perichondrium grafts in terms of graft healing and hearing results. PMID- 21035290 TI - Differentiated posterior cervical liposarcoma with carcinoid: report of a case. AB - Liposarcoma most commonly arises in the retroperitoneum and lower extremities. Liposarcoma of the head and neck region is a rare and potentially life threatening malignancy. Those originating in the right retrocervical space cause special diagnostic and therapeutic difficulties. In present report, a case of differentiated liposarcoma of the right cervical region with intestinal carcinoid is reported. The tumor continued to grow slowly over 3 years before a definitive diagnosis was established. Extended extirpation of the tumor and modified radical neck dissection, postoperative radiotherapy followed by chemotherapy were performed and proved to be efficacious in that no recurrence was observed for 2 years. Recommendations for earlier and correct diagnosis and treatment of this rare neoplasm are discussed. PMID- 21035291 TI - Rheometric properties of canine vocal fold tissues: variation with anatomic location. AB - OBJECTIVE: To evaluate the in vitro rheometric properties of the canine vocal fold lamina propria and muscle at phonatory frequencies, and their changes with anatomic location. METHODS: Six canine larynges were harvested immediately postmortem. Viscoelastic shear properties of anterior, middle, and posterior portions of the vocal fold cover (lamina propria) as well as those of the medial thyroarytenoid (TA) muscle (vocalis muscle) were quantified by a linear, controlled-strain simple-shear rheometer. Measurements of elastic shear modulus (G') and dynamic viscosity (eta') of the specimens were conducted with small amplitude sinusoidal shear deformation over a frequency range of 1-250Hz. RESULTS: All specimens showed similar frequency dependence of the viscoelastic functions, with G' gradually increasing with frequency and eta' decreasing with frequency monotonically. G' and eta' of the canine vocalis muscle were significantly higher than those of the canine vocal fold cover, and eta' of the canine vocal fold cover was significantly higher than that of the human vocal fold cover. There were no significant differences in G' and in eta' between different portions of the canine vocal fold cover. CONCLUSION: These preliminary data based on the canine model suggested that the vocalis muscle, while in a relaxed state in vitro, is significantly stiffer and more viscous than the vocal fold cover during vibration at phonatory frequencies. For large-amplitude vocal fold vibration involving the medial portion of the TA muscle, such distinct differences in viscoelastic properties of different layers of the vocal fold should be taken into account in multi-layered biomechanical models of phonation. PMID- 21035292 TI - A case report of HTLV-I associated myelopathy presenting with cerebellar ataxia and nystagmus. AB - HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP) is characterized by spastic paraparesis in the lower extremities, and urinary disturbance. HAM/TSP has also been less frequently associated with cerebellar syndromes and nystagmus. We report a case of HAM/TSP presenting with cerebellar ataxia and nystagmus. The patient was a 73-year-old woman who was born in southern Japan. At age 41, she developed pain and spasticity in the bilateral lower limbs and gradually progressive gait disturbance. At age 57, she was diagnosed with HAM/TSP based on spastic paraparesis in the lower limbs, urinary disturbance and positive anti HTLV-I antibody in serum and cerebrospinal fluid. In June 2008, she was referred to our university and hospitalized for rehabilitation. Twenty days later, she experienced rotatory vertigo sensation. Magnetic resonance imaging revealed pontocerebellar atrophy. The patient presented with cerebellar signs in the upper limbs, gaze-evoked nystagmus in the sitting position and right-beating horizontal nystagmus in the supine and head hanging positions. Electronystagmography (ENG) showed horizontal saccadic overshoot dysmetria and horizontal saccadic pursuit. Nystagmus is rare among the literature on HAM/TSP. ENG is helpful to evaluate and confirm the cerebellar syndromes of HAM/TSP. PMID- 21035293 TI - Tilting the jaw to improve the image quality or to reduce the dose in cone-beam computed tomography. AB - OBJECTIVE: The image quality in cone-beam computed tomography (CBCT) should be improved tilting the mandible that contains two dental titanium implants, within the relevant range of motion. MATERIALS AND METHODS: Using the mandible of a five month-old pig, CBCT was performed varying the accelerating voltage, beam current, the starting rotation angle of the mandible in the source-detector plane and the tilt angles of the jaw with respect to the source-detector plane. The different datasets were automatically registered with respect to micro CT data to extract the common volume and the deviance to the pre-defined standard that characterizes the image quality. RESULTS: The variations of the accelerating voltage, beam current and the rotation within the source-detection plane provided the expected quantitative behavior indicating the appropriate choice of the imaging quality factor. The tilting of the porcine mandible by about 14 degrees improves the image quality by almost a factor of two. CONCLUSIONS: The tilting of the mandible with two dental implants can be used to significantly reduce the artifacts of the strongly X-ray absorbing materials in the CBCT images. The comparison of 14 degrees jaw tilting with respect to the currently recommended arrangement in plane with the teeth demonstrates that the applied exposure time and the related dose can be reduced by a factor of four without decreasing the image quality. PMID- 21035294 TI - Pseudolisthesis secondary to small L5. AB - RATIONALE AND OBJECTIVE: Small AP diameter of L5 can mimic spondylolisthesis in lumbosacral MRI. The aim of the present study was to evaluate the prevalence of small L5 mimicking spondylolisthesis in lumbosacral MRI of the patients referred to an imaging center by any symptoms. Association between small anteroposterior diameter of L5 and presence and absence of unilateral or bilateral spondylolysis at L5 were also evaluated. MATERIALS AND METHODS: 2000 lumbosacral MRI of the patients referred to an imaging center for any reasons were evaluated. The posterior step of L5 was measured and the cases with posterior step of more than 2 mm were selected. These cases were evaluated for presence or absence of spondylolysis. RESULTS: Small anteroposterior diameters of L5 were detected in 38 cases (2%), mimicking the spondylolisthesis in lumbosacral MRI. The prevalence of small L5 in lumbosacral MRI of the patients referred by any symptoms was about 2%. In these selected cases, 6 (15.8%) show unilateral spondylolysis and 5 (13.1%) show bilateral spondylolysis. CONCLUSION: Pseudospondylolisthesis secondary to small AP diameter of L5 has prevalence of about 2% in lumbosacral MRI of cases referred for any reasons and can be overlooked in reporting of LS MRI. There was an association between small anteroposterior diameter of L5 and presence of spondylolysis at L5. PMID- 21035295 TI - Analysis of cephalosporins by hydrophilic interaction chromatography. AB - A simple hydrophilic interaction chromatography (HILIC) method was developed to analyze seven cephalosporins. These seven cephalosporins could be separated well on the Click beta-CD column and Atlantis HILIC Silica column. The effects of buffer concentration and pH on the retention under HILIC mode were studied. Except cefepime hydrochloride (4), the retention of other six cephalosporins increased with increasing buffer concentration, while decreased with increasing pH. Different separation selectivities could be observed on the Click beta-CD column and Atlantis HILIC Silica column, and changing pH also resulted in the changing of separation selectivity. The separations of cephalosporins by HILIC and reversed-phase high performance liquid chromatography (RP-HPLC) were compared, and the two separation modes had good orthogonality. In addition, cefotaxime sodium (1) and its degradation were separated well on the Click beta CD column, which indicated that the Click beta-CD column by HILIC can be used for studying the stability of cephalosporins. PMID- 21035296 TI - Provider communication and patient participation in diabetes self-care. AB - OBJECTIVE: To determine the effect size of provider communication about self-care and the provider's following treatment guidelines on the self-care behaviors of people with Type 2 diabetes (T2DM). METHODS: Data were from the TRIAD telephone surveys of Michigan patients in managed care with T2DM (n=1438). The survey asked about the patients' self-care and provider communication about blood glucose monitoring, exercise, foot care, flu vaccination and annual retina screening. RESULTS: After controlling for patient socio-demographics and disease severity, remembering having received provider information on these activities more than doubled the odds of performing blood glucose monitoring, and performing foot examinations. It also significantly increased the amount of exercise the patient performed. Provider modeling had a strong association with foot care. Counseling by a diabetes educator was positively and significantly associated with having an annual retina examination and receiving an influenza vaccination. CONCLUSIONS: Remembering self-care information is associated with increased home based self care by patients and their families. Consulting with a diabetes educator can substantially improve patient self-care. PRACTICE IMPLICATIONS: Health care providers should encourage patient education. However, physician time is costly and most nurses do not specialize in patient education; one solution is to refer patients to a diabetes educator. PMID- 21035297 TI - A hierarchy of needs? Embryo donation, in vitro fertilisation and the provision of infertility counselling. AB - OBJECTIVE: The aim of the paper is to examine how those working in, using and regulating assisted conception clinics discussed infertility counselling and its provision within the context of embryo donation and in vitro fertilisation. METHOD: 35 participants were recruited for semi-structured, face-to-face interviews. All data were analysed using thematic analysis. RESULTS: The thematic analysis revealed recurring themes based upon the portrayals of infertility counselling, embryo donation and in vitro fertilisation. CONCLUSIONS: This paper suggests that an implicit hierarchy exists around those using assisted conception techniques and their infertility counselling requirements, which was dependent upon the assisted conception technique used. As a result, some people using assisted conception techniques felt that their needs had been overlooked due to this covert hierarchy. PRACTICE IMPLICATIONS: Those working in, using or regulating assisted conception clinics should not view infertility counselling as restricted to treatments involving donation, or solely for people within the clinical system. PMID- 21035299 TI - [Primary lymphedema of limbs]. AB - Limb lymphedema is frequent and not well-known. Clinical classification distinguishes primary lymphedemas due to developmental disorders of the lymphatic system (hereditary or not, sometimes associated with other malformations) and secondary lymphedemas. Primary lymphedema is a lymphedema without a cause to explain lymphatic impairment. It is due to an abnormal lymphangiogenesis in utero. It is often associated with mutation in a gene involved in lymphangiogenesis (FOX C2, VEGFR 3, SOX18, PROX 1...). To assess clinical diagnosis, non-invasive techniques are able to study structure and function of the lymphatic system (mainly isotopic lymphography). Treatment is the complex decongestive therapy which associates manual lymphatic drainage and bandage. Predisposing or precipitating factors have to be treated (particularly streptococcal infections). Surgical treatment has precise and rare indication. PMID- 21035300 TI - Hospital mortality rates: how is palliative care taken into account? AB - CONTEXT: Using mortality rates to measure hospital quality presumes that hospital deaths are medical failures. To be a fair measure of hospital quality, hospital mortality measures must take patient-level factors, such as goals of care, into account. OBJECTIVES: To answer questions about how hospital mortality rates are computed and how the involvement of hospice or palliative care (PC) are recognized and handled. METHODS: We analyzed the methods of four entities: Centers for Medicare & Medicaid Services "Hospital Compare;" U.S. News & World Report "Best Hospitals;" Thomson-Reuters "100 TopHospitals;" and HealthGrades. RESULTS: All entities reviewed rely on Medicare data, compute risk-adjusted mortality rates, and use "all-cause" mortality. They vary considerably in their recognition and handling of cases that involved hospice care or PC. One entity excludes cases with prior hospice care and another excludes those discharged to hospice at the end of the index hospitalization. Two entities exclude some or all cases that were coded with the V66.7 "Palliative Care Encounter" International Classification of Disease, Ninth Revision, Clinical Modification diagnosis code. CONCLUSION: Proliferation of, and variability among, hospital mortality measures creates a challenge for hospital administrators. PC and hospice leaders need to educate themselves and their hospital administrators about the extent to which these mortality rates take end-of-life care into account. At the national level, PC and hospice leaders should take advantage of opportunities to engage these mortality raters in conversation about possible changes in their methods and to conduct further research on this topic. PMID- 21035298 TI - Patient-physicians' information exchange in outpatient cardiac care: time for a heart to heart? AB - OBJECTIVE: Agreement between patients and physicians is an indicator of successful communication. Concordance in domains of communication among patients with heart disease and communication barriers has not been studied. METHODS: English, Spanish, or Cantonese-speaking patients seen at a public hospital cardiology clinic were assessed with pre-visit questionnaires. Surveys of patients and their physicians immediately after the visit asked each about: (1) cardiac functional status, (2) barriers to self-management, (3) cardiac diagnoses, and (4) treatment. We assessed patient-physician concordance in these domains. RESULTS: 179 patients and 56 physicians completed the study. Patients had low educational attainment, limited literacy and limited English proficiency. Physicians underestimated patients' cardiac functioning status (NYHA Classes 2 4), by 1 class or more in 50% of visits. Physicians were frequently unaware of medication (38/57, 67%) and psychosocial (61/88, 69%) barriers. Patients were unable to describe even 1 matching diagnosis (72/170, 42% concordant) among 5 categories. Physicians' reported medication changes in 106/179 (59%) but patients failed to report these changes in 55% (58/106). Multivariate logistic regression analyses showed no significant association between patient characteristics and concordance. CONCLUSION: Patients and physicians often fail to communicate effectively and determinants of concordance in CVD care require further investigation. PRACTICE IMPLICATIONS: Developing strategies to improve communication within the medical encounter are critical to improving ambulatory chronic disease management. PMID- 21035301 TI - Left ventricular structure and function in children with and without developmental coordination disorder. AB - Children with developmental coordination disorder (DCD) are more likely to develop cardiovascular disease risk factors such as obesity and reduced cardio respiratory fitness. However, there is limited data using laboratory measures for assessing the risk of cardiovascular disease associated with DCD. The purpose of this study was to examine differences in left ventricular structure and function between children with DCD and healthy controls. The study involved 126 children (aged 12-13 years) with significant motor impairment (n = 63) and healthy controls (n = 63) matched for age, sex, and school. The Movement ABC test (M ABC2) was used to classify children as probable DCD (p-DCD). Cardiac dimensions were measured using ultrasound echocardiography. Left ventricular mass (LVM) was elevated in children with p-DCD (89 +/- 17 g) compared to controls (87 +/- 21 g), however, this difference was not significant. When LVM was normalized to height(2.7), no difference was evident between groups (26 g and 26 g for the p DCD and controls, respectively). However, the p-DCD group demonstrated significantly elevated stroke volume (p = 0.02), cardiac output (p<0.001), end diastolic volume (p = 0.03), and left ventricle diameter in diastole (p = 0.02). Also, peak VO(2) normalized for fat free mass (FFM) was significantly lower (p = 0.001) and systolic blood pressure (p = 0.01), body mass index (p = 0.001), heart rate (p = 0.005) and percent body fat (p<0.001) were significantly higher in p DCD. In regression analyses, p-DCD was a significant predictor of stroke volume and cardiac output even after accounting for height, FFM, VO(2FFM), and sex. Children with p-DCD do not demonstrate significantly elevated LVM or depressed systolic function compared to healthy controls. However, cases with p-DCD demonstrate significantly elevated end-diastolic volume, diastolic chamber size, stroke volume, and cardiac output. These differences indicate obesity related changes in the left ventricle and may represent the early stages of developing left ventricle hypertrophy. PMID- 21035302 TI - Handwriting characteristics among secondary students with and without physical disabilities: a study with a computerized tool. AB - The purpose of the present study was to investigate the handwriting characteristics of secondary school students with and without physical disabilities (PD). With the use of a computerized Chinese Handwriting Assessment Tool (CHAT), it was made possible to objectively assess and analyze in detail the handwriting characteristics of individual students. Fifty participants (age range: 15-19-years-old) were recruited from one mainstream secondary school and 20 participants (age range: 17-24-years-old) were recruited from two secondary schools for students with PD. They were asked to perform three consecutive handwriting tasks: copying 90 characters using the computerized CHAT, an English passage copying task, and a Chinese passage copying task. The data indicated that students with PD were significantly slower in copying both Chinese and English characters in passages when compared to the typical students. Significant differences in the measures of writing speed, air/ground time ratio, standard deviation of speed, standard deviation of size per character, and number of stroke errors measured by the CHAT were found between the two groups of students. Further analysis on the data of typical students indicated no significant difference in handwriting speed among students of different classes (i.e. arts or science) on copying Chinese and English passages, and on individual Chinese words (from CHAT). The academic results of students also showed no significant correlation with their handwriting speed measured by the three writing tasks. To conclude, the CHAT system was able to identify a number of characteristics of handwriting on students with and without PD. It was suggested that the CHAT should further be developed into an objective evaluation tool to explore the handwriting characteristics of the students with a wider range of disabilities in the future, and to make recommendations to arrange special examination arrangements (SEA) for students with physical disabilities or other special needs. PMID- 21035303 TI - Colour and contrast enhancement for improved skin lesion segmentation. AB - Accurate extraction of lesion borders is a critical step in analysing dermoscopic skin lesion images. In this paper, we consider the problems of poor contrast and lack of colour calibration which are often encountered when analysing dermoscopy images. Different illumination or different devices will lead to different image colours of the same lesion and hence to difficulties in the segmentation stage. Similarly, low contrast makes accurate border detection difficult. We present an effective approach to improve the performance of lesion segmentation algorithms through a pre-processing step that enhances colour information and image contrast. We combine this enhancement stage with two different segmentation algorithms. One technique relies on analysis of the image background by iterative measurements of non-lesion pixels, while the other technique utilises co operative neural networks for edge detection. Extensive experimental evaluation is carried out on a dataset of 100 dermoscopy images with known ground truths obtained from three expert dermatologists. The results show that both techniques are capable of providing good segmentation performance and that the colour enhancement step is indeed crucial as demonstrated by comparison with results obtained from the original RGB images. PMID- 21035305 TI - The susceptibility of Aire(-/-) mice to experimental myasthenia gravis involves alterations in regulatory T cells. AB - The autoimmune regulator (Aire) is involved in the prevention of autoimmunity by promoting thymic expression of tissue restricted antigens which leads to elimination of self-reactive T cells. We found that Aire knockout (KO) mice as well as mouse strains that are susceptible to experimental autoimmune myasthenia gravis (EAMG) have lower thymic expression of acetylcholine receptor (AChR- the main autoantigen in MG), compared to wild type (WT) mice and EAMG-resistant mouse strains, respectively. We demonstrated that Aire KO mice have a significant and reproducible lower frequency of CD4+Foxp3+ cells and a higher expression of Th17 markers in their thymus, compared to wild type (WT) mice. These findings led us to expect that Aire KO mice would display increased susceptibility to EAMG. Surprisingly, when EAMG was induced in young (2 month-old) mice, EAMG was milder in Aire KO than in WT mice for several weeks until the age of about 5 months. However, when EAMG was induced in relatively aged (6 month-old) mice, Aire KO mice presented higher disease severity than WT controls. This age-related change in susceptibility to EAMG correlated with an elevated proportion of Treg cells in the spleens of young but not old KO, compared to WT mice, suggesting a role for peripheral Treg cells in the course of disease. Our observations point to a possible link between Aire and Treg cells and suggest an involvement for both in the pathogenesis of myasthenia. PMID- 21035304 TI - Diffusion tensor-based fast marching for modeling human brain connectivity network. AB - Diffusion tensor imaging (DTI) is an effective modality in studying the connectivity of the brain. To eliminate possible biases caused by fiber extraction approaches due to low spatial resolution of DTI and the number of fibers obtained, the fast marching (FM) algorithm based on the whole diffusion tensor information is proposed to model and study the brain connectivity network. Our observation is that the connectivity extracted from the whole tensor field would be more robust and reliable for constructing brain connectivity network using DTI data. To construct the connectivity network, in this paper, the arrival time map and the velocity map generated by the FM algorithm are combined to define the connectivity strength among different brain regions. The conventional fiber tracking-based and the proposed tensor-based FM connectivity methods are compared, and the results indicate that the connectivity features obtained using the FM-based method agree better with the neuromorphical studies of the human brain. PMID- 21035306 TI - Dietary fiber and serum 16alpha-hydroxyestrone, an estrogen metabolite associated with lower systolic blood pressure. AB - OBJECTIVE: We recently identified an inverse relation between systolic blood pressure (SBP) and serum 16alpha-hydroxyestrone, a metabolite of 17beta estradiol, in postmenopausal women. Formation of 16alpha-hydroxyestrone is catalyzed primarily by CYP1A2, a cytochrome P450 enzyme. The objective of this study was to evaluate the relations between known modifiers of CYP1A2 activity and serum 16alpha-hydroxyestrone in postmenopausal women. We hypothesized that fruits, vegetables, and grains, which contain more soluble fiber (a known inducer of CYP1A2) as a proportion of total fiber, would be more positively associated with serum 16alpha-hydroxyestrone than legumes, which contain less soluble fiber as a proportion of total fiber. METHODS: Serum from a population-based sample of 42 postmenopausal women 55 to 69 y of age living in Cook County, Illinois, was assayed for 16alpha-hydroxyestrone using mass spectrometry. Ordinal logistic regression was used to evaluate the cross-sectional relation between dietary fiber and serum 16alpha-hydroxyestrone after adjusting for multiple covariates. RESULTS: Compared with dietary fiber from legumes, dietary fiber from fruits and vegetables was associated with a greater log odds (B=0.201, P=0.036) of having higher serum concentrations of 16alpha-hydroxyestrone. The log odds of having higher serum concentrations of 16alpha-hydroxyestrone was also lower in African American women (B=-2.300, P=0.030) compared with white women. CONCLUSION: These results are consistent with previous studies demonstrating a negative relation between SBP and dietary fruits and vegetables and a positive relation between African-American race and SBP. Further research is needed regarding dietary factors that may influence the serum concentration of 16alpha-hydroxyestrone. PMID- 21035307 TI - Influence of different doses of retinoic acid on cardiac remodeling. AB - OBJECTIVE: The role of retinoic acid in promoting postnatal heart alterations is still unclear. The aim of this study was to evaluate whether the cardiac alterations caused by all-trans- retinoic acid (ATRA) in normal adult rat hearts are physiologic or pathologic and if these alterations are dose-dependent. METHODS: Rats were allocated into a control group that received a diet without ATRA (n=16), a group that received 0.3 mg of ATRA/kg of diet (n=17), a group that received a diet containing 10 mg of ATRA/kg (n=18), or a group that received 50 mg of ATRA/kg in the diet (n=18). After 4 wk, the animals were evaluated echocardiographically, morphologically, and biochemically. RESULTS: The 50-mg ATRA group presented cardiac hypertrophy with maintenance of cardiac geometry and increased systolic function, whereas diastolic function was similar to that of the control group. In addition, progressive increases in the ATRA dose resulted in gradual augmentations of left atrial diameter, left ventricular diastolic and systolic diameters, left ventricular mass index, cardiac output, cardiac index, and aortic velocity. The ATRA did not produce alterations in interferon-gamma and tumor necrosis factor-alpha cardiac levels, interstitial collagen volume fraction, or the intensity and localization of connexin-43. In addition, no alteration was observed in beta-hydroxyacyl coenzyme A dehydrogenase, lactate dehydrogenase, or citrate synthase, suggesting that cardiac energetic metabolism was preserved with ATRA. CONCLUSION: These results suggest that ATRA produced dose-dependent effects and cardiac remodeling that is more compatible with a physiologic response. PMID- 21035309 TI - Zinc-suppressed inflammatory cytokines by induction of A20-mediated inhibition of nuclear factor-kappaB. AB - OBJECTIVE: Chronic generation of inflammatory cytokines and reactive oxygen species are implicated in atherosclerosis, aging, cancers, and other chronic diseases. We hypothesized that zinc induces A20 in premonocytic, endothelial, and cancer cells, and A20 binds to tumor necrosis factor (TNF)-receptor associated factor, and inhibits Ikappa kinase-alpha (IKK-alpha)/nuclear factor-kappaB (NF kappaB), resulting in downregulation of TNF-alpha and interleukin-1beta (IL 1beta). METHODS: To test this hypothesis, we used HL-60, human umbilical vein endothelial cells, and SW480 cell lines under zinc-deficient and zinc-sufficient conditions in this study. We measured oxidative stress markers, inflammatory cytokines, A20 protein and mRNA, A20-FRAF-1 complex, and IKK-alpha/NF-kappaB signaling in stimulated zinc-deficient and zinc sufficient cells. We also conducted antisense A20 and siRNA studies to investigate the regulatory role of zinc in TNF-alpha and IL-1beta via A20. RESULTS: We found that zinc increased A20 and A20-tumor necrosis factor-receptor associated factor-1 complex, decreased the IKK-alpha/NF-kappaB signaling pathway, oxidative stress markers, and inflammatory cytokines in these cells compared with zinc-deficient cells. We confirmed that zinc-induced A20 contributes to downregulation of TNF-alpha and IL-1beta by antisense and short interfering RNA A20 studies. CONCLUSION: Our studies suggest that zinc suppresses generation of NF-kappaB-regulated inflammatory cytokines by induction of A20. PMID- 21035310 TI - Risk factors of neurosensory deficits in lower third molar surgery: an literature review of prospective studies. AB - This literature review assessed the risk factors linked to inferior dental nerve (IDN) and lingual nerve (LN) deficits following lower wisdom tooth surgery. A computer search of several databases with specified key words was performed. 32 articles were selected; the risk factors for IDN deficit were reported in 4 articles, LN in 9 and both IDN and LN in 19. Data were analysed statistically to evaluate the potential risk factors. Literature review showed specific radiographic signs and intra-operative IDN exposure increased the risk of IDN deficit. Raising the lingual flap significantly increased the risk of LN deficit. Unerupted tooth and lingual split technique increased IDN and LN deficit risks significantly. Age was linked to IDN and LN deficits, and deep impaction was related to IDN deficit, but no statistical tests were performed on these two risk factors owing to the heterogeneity of data from the studies. This literature review found increased age, unerupted tooth, deep impaction, specific radiographic signs, intra-operative IDN exposure and lingual split technique were risk factors for IDN deficit; increased age, unerupted tooth, distal impaction, raising of lingual flap and lingual split technique were risks factors for LN deficit in lower wisdom tooth surgery. PMID- 21035308 TI - Brain fuel metabolism, aging, and Alzheimer's disease. AB - Lower brain glucose metabolism is present before the onset of clinically measurable cognitive decline in two groups of people at risk of Alzheimer's disease--carriers of apolipoprotein E4, and in those with a maternal family history of AD. Supported by emerging evidence from in vitro and animal studies, these reports suggest that brain hypometabolism may precede and therefore contribute to the neuropathologic cascade leading to cognitive decline in AD. The reason brain hypometabolism develops is unclear but may include defects in brain glucose transport, disrupted glycolysis, and/or impaired mitochondrial function. Methodologic issues presently preclude knowing with certainty whether or not aging in the absence of cognitive impairment is necessarily associated with lower brain glucose metabolism. Nevertheless, aging appears to increase the risk of deteriorating systemic control of glucose utilization, which, in turn, may increase the risk of declining brain glucose uptake, at least in some brain regions. A contributing role of deteriorating glucose availability to or metabolism by the brain in AD does not exclude the opposite effect, i.e., that neurodegenerative processes in AD further decrease brain glucose metabolism because of reduced synaptic functionality and hence reduced energy needs, thereby completing a vicious cycle. Strategies to reduce the risk of AD by breaking this cycle should aim to (1) improve insulin sensitivity by improving systemic glucose utilization, or (2) bypass deteriorating brain glucose metabolism using approaches that safely induce mild, sustainable ketonemia. PMID- 21035311 TI - Thalidomide for treatment of refractory epilepsy. AB - We have experimentally shown that thalidomide has strong anticonvulsant properties. In an open label study, eight male patients with refractory epilepsy received thalidomide at daily-doses of 200 mg during 1 year, frequency of seizures before and during treatment were compared. The mean number of seizures before thalidomide administration was 26 +/- 4 per month; it decreased to 7 +/- 1 along thalidomide therapy. Our results indicate that thalidomide has strong therapeutic effects in refractory epilepsy. PMID- 21035312 TI - The epidemiology of epilepsy in the Russian Federation. AB - This study is the first analysis of the epidemiology of epilepsy in the Russian Federation (RF), in the English medical literature. The RF is geographically the largest territory in the world with a population of 142 million. The study evaluated prevalence of epilepsy in older teenagers and adults in 14 regions of the RF with total population of 517,624 persons (about 0.34% of all the population of the RF). Study sites were located in both European (Western population) and Siberian (Eastern population) regions of Russia. We identified 1753 patients with established epilepsy (1033 men, 720 women) from available medical information sources. Epilepsy cases were evaluated by study neurologists or epileptologists; all the patients underwent EEG, one third - neuroimaging. The age adjusted prevalence of epilepsy, standardized to the European Standard Million was 3.40 (95%CI: 3.26-3.55) per 1000. Prevalence was higher among men 4.50 (95%CI: 4.25-4.76) than among women-2.52 (95%CI: 2.35-2.69) (p < 0.0001). Prevalence in the Eastern population was significantly higher than in the Western population. The highest prevalence was found in the age group 50-59 years. Localization-related (focal) epilepsies/epilepsy syndromes were diagnosed in the majority (81.6%). In about one-third of those with localization-related epilepsies etiology remained undetermined. Head injury was the main identified cause of epilepsy, followed by cerebrovascular disorders. CONCLUSION: The prevalence of epilepsy in the population >= 14 y.o. in Russia is consistent with results of the studies in adults in other European countries, although at lower end of the range. Age and gender trends are similar. PMID- 21035313 TI - Predictive validity of clinical variables in the "at risk" for psychosis population: international comparison with results from the North American Prodrome Longitudinal Study. AB - BACKGROUND: There has been recent optimism with regard to improving the predictive validity of those individuals who develop a psychotic disorder from the "Ultra High Risk" (UHR) or putatively prodromal population using combinations of clinical variables. We aimed to test the recent results from a large collaborative consortium in an independent cohort from the PACE (Personal Assistance and Clinical Evaluation) clinic in Australia. METHOD: The North American Prodrome Longitudinal Study (NAPLS) consortium study reported 5 important clinical predictive variables within their US sample of UHR patients: genetic risk with functional decline; high unusual thought content score; high suspicion/paranoia score; low social functioning and history of substance abuse. We examined the predictive validity of these variables using data from a cohort of 104 UHR patients from the PACE clinic in Melbourne, Australia. Cox regression was used to explore the relationship between these variables at baseline and transition to psychosis by 28months. RESULTS: Three of the five variables were found to be associated with transition in our sample: high unusual thought content scores; low functioning; and having genetic risk with functional decline. A combination of two out of three of these features produced a reasonable predictive validity (positive predictive value (PPV) 65.4%, sensitivity 37.3%, and specificity 87.2%) but with overall lower PPVs than that reported by the NAPLS consortium. CONCLUSIONS: Three out of five of the identified clinical predictors for transition to psychosis from the NAPLS study were replicated in an independent sample. Using a combination of clinical variables the predictive validity of determining whether a UHR individual develops a psychotic disorder was improved above UHR criteria alone. Although psychosis prediction is improved using this model, the probability of a person not developing psychotic disorder is still quite high at 35%. PMID- 21035314 TI - Development of impedimetric and optical calcium biosensor by using modified gold electrode with porcine S100A12 protein. AB - We describe the development of a label free method to analyze the interactions between Ca(2+) and the porcine S100A12 protein immobilized on polyvinyl butyral (PVB). The modified gold electrodes were characterized using cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), scanning electron microscopy (SEM) and surface plasmon resonance (SPR) techniques. SEM analyses of PVB and PVB S100A12 showed a heterogeneous distribution of PVB spherules on gold surface. EIS and CV measurements have shown that redox probe reactions on the modified gold electrodes were partially blocked due the adsorption of PVB-S100A12, and confirm the existence of a positive response of the immobilized S100A12 to the presence of calcium ions. The biosensor exhibited a wide linear response to Ca(2+) concentrations ranging from 12.5 to 200mM. The PVB-S100A12 seems to be bound to the gold electrode surface by physical adsorption; we observed an increase of 1184.32m degrees in the SPR angle after the adsorption of the protein on the PVB surface (in an indication that 9.84ng of S100A12 are adsorbed per mm(2) of the Au PVB electrode), followed by a further increase of 581.66m degrees after attachment of the Ca(2+) ions. In addition, no SPR response is obtained for non specific ions. These studies might be useful as a platform for the design of new reusable and sensitive biosensing devices that could find use in the clinical applications. PMID- 21035315 TI - [EBV infection revealing a long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency in a 3-year-old boy]. AB - OBSERVATION: We report on the case of a 3-year-old child from La Reunion island, who presented with hypoglycemic hypoketotic coma secondary to a primary Epstein Barr virus (EBV) infection. The discovery of the G1528C homozygote mutation provided the diagnosis of long-chain-3-hydroxyacyl-CoA-dehydrogenase (LCHAD); an adapted dietary plan with prevention of fasting and L-carnitine supplementation was initiated. After 2 years, a pigmentary retinopathy appeared and muscle weakness increased. COMMENTS: Isolated LCHAD deficiency is an autosomal recessive disorder of fatty acid metabolism. Prevalence is about 1-9/100,000 and diagnosis is often made before the age of 2 years. The late age of revelation in our case is related to a spontaneous diet without animal fats (disgust for meat, diet based on white rice and skimmed milk) and nighttime breastfeeding until the age of 3 years. In an affected fetus, heterozygous mothers are susceptible to developing a hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome or an acute fatty liver pregnancy (AFLP) syndrome during the 3rd trimester of pregnancy, which motivated us to set up a systematic neonatal screening program and a specific monitoring of these newborns. PMID- 21035316 TI - Antioxidant and anti-atherogenic activities of three Piper species on atherogenic diet fed hamsters. AB - Atherogenic diet is known to induce high plasma lipid concentration, oxidative stress and early atherosclerosis. Antioxidants have potentials to counter the effect of atherogenic diet. The present research aims at evaluating the antioxidant and anti-atherosclerotic activities of three Piper species (Piper guineense, Piper nigrum and Piper umbellatum) on atherogenic diet fed hamsters. Hamsters divided into 8 groups: normal control, atherosclerotic control and six test groups. The normal animals fed normal rodent chow, the atherosclerotic control animals fed the same rodent chow supplemented with 0.2% cholesterol and 10% coconut oil (high cholesterol diet). The 6 test groups' animals fed same diet as the atherosclerotic control group but with additional supplementation of 2 graded doses (1 and 0.25 mg/kg body weight, o.p.) of plant extracts for 12 weeks. The atherogenic diet induced a collapse of the erythrocyte antioxidant defense system (significant decrease in superoxide dismutase, catalase and glutathione peroxidase activities). Atherogenic diet also induced an increase in plasma total cholesterol, triglyceride, thiobarbituric acid reactive substances (TBARS), oxidation of low density lipoprotein cholesterol (LDL) and accumulation of foam cells in the aorta a hall mark for atherosclerosis. Administration of the Piper species prevented the collapse of the antioxidant system and the increase of plasma parameters maintaining them towards normality. The Piper species also prevented LDL oxidation by increasing the time (lag time) for its oxidation. The results suggest that these Piper species have significant antioxidant and anti atherogenic effect against atherogenic diet intoxication. PMID- 21035317 TI - Synergistic effects of parthenolide and benznidazole on Trypanosoma cruzi. AB - Parthenolide previously isolated from Tanacetum vulgare was tested for its in vitro combinatory effect with benznidazole against Trypanosoma cruzi. Parthenolide showed a strong synergistic activity against epimastigote forms, reducing 23-fold the concentration of benznidazole necessary to inhibit 50% of cell growth (IC(50) of 1.6 to 0.07 MUg/ml) when in combination with parthenolide. In addition, an additive effect against trypomastigote forms (FIC 1.06), followed by an antagonistic effect on the cytotoxicity (FIC 2.36), was observed for the combination of both drugs. Parthenolide induced morphological alterations in the body shape of trypomastigote forms, causing rounding and shortening of the parasite and loss of integrity of the plasma membrane, as previously described by other workers. PMID- 21035318 TI - Bronchodilator treatment and asthma death: a new analysis of a British case control study. AB - We investigated the relationship between asthma mortality and long-acting beta(2) agonists (LABA), including interactions with age, inhaled corticosteroids (ICS) and social deprivation. We used a new, expanded dataset of recorded medication extracted blind from the anonymised primary care records of an earlier British case-control study. The cases were 532 asthma deaths aged < 65 occurring between 1994 and 1998 and the controls were 532 asthma admissions, matched for age, hospital, and index date (date of death/asthma admission). The exposure periods prior to the index date were current (<= 2 months) or recent ( > 2-6 months). We found no evidence of an overall association with current (OR = 0.89 [95% confidence interval 0.61-1.30]) or recent (1.08 [0.76-1.53]) mention of LABA, but there was some evidence of a positive interaction with age. Among controls with mention of LABA, a concurrent mention of ICS (within 1 month) was common (85% and 93% for the two respective periods) which limited our power to investigate any interaction between LABA and ICS. There was no coherent evidence of effect modification by social deprivation. In a population based case-control study where prescription of LABA without concomitant ICS was uncommon there was no evidence of an overall association between LABA and asthma death. PMID- 21035319 TI - A cost-of-illness study estimating the direct cost per asthma exacerbation in Turkey. AB - OBJECTIVE: To calculate direct cost per asthma exacerbation at tertiary healthcare centers across Turkey. METHODS: A total of 294 persistent asthma patients (mean age: 50.4+/-15.1 years) were included in this retrospective study upon admission with an acute asthma attack. Direct costs including drug treatment, non-drug treatment, healthcare resource utilization, emergency care, tests and consultations were calculated per asthma attack in relation to asthma attack severity. RESULTS: The asthma attack was moderate in 57.5% of the patients. Direct cost was ?214.9 (95% CI: 183.9; 245.8) per attack. The cost of severe attack ?308.2 (95% CI: 258.2; 358.2)] was significantly higher than moderate [?172.6 (95% CI: 155.1; 190.2)] and mild [?128.6 (95% CI: 102.6; 154.7) attacks. It was also significantly higher for inpatient follow-up [?257.7 (95% CI: 220.4; 295)] vs. outpatient follow-up [?54.5 (95% CI: 47; 62; p<0.001)] and uncontrolled asthma [?288.2 (95% CI: 216.7; 359.6)] vs. controlled [?128.9 (95% CI: 92.1; 165.8); p<0.01] asthma. CONCLUSION: Health policies targeting achievement of better asthma control and lower disease severity during the stable periods of the disease as well as appropriate hospitalization of patients and rational prescribing of drugs will play crucial role in the reduction of economic burden of asthma for the patient and the society. PMID- 21035320 TI - Facile fabrication of distance-tunable Au-nanorod chips for single-nanoparticle plasmonic biosensors. AB - In this work, we present a simple and effective method to fabricate distance controllable, Au nanorod (AuNR) chips thorough electrostatic assembly. Cetyltrimethylammonium bromide (CTAB)-capped AuNRs were immobilized on a hydroxyl functionalized glass substrate by immersion of the glass into AuNR-suspension. The electrostatic surfacial assembly of AuNRs offers significant advantages over conventional thiol-induced chemistry, i.e., direct control of self-assembly of AuNRs, easy fabrication in ambient environment and most importantly, broad range of tunable inter-particle distance, ranging from 0.25 to 10 MUm. The mechanism of time-dependant deposition process of AuNRs was described via competitive bindings of AuNRs and free CTAB molecules in AuNR-suspension. In addition, the electrostatically anchored AuNRs on a glass substrate provide sufficient stability under harsh experimental conditions with flow of basic/acidic solutions and organic solvents with different polarity. The feasibility of the AuNR-chips fabricated by the proposed method for single-nanoparticle plasmonic biosensors was demonstrated by the plasmonic measurement of aptamer-thrombin binding event. The corresponding limit of detection of thrombin molecule was found to be ~278 pM based on the signal to noise ratio of 4. PMID- 21035321 TI - A new strategy for photoelectrochemical DNA biosensor using chemiluminescence reaction as light source. AB - Physical light source is absolutely necessary for usual photoelectrochemical measurement. In this work, chemiluminescence reaction rather than physical light source was used for the development of a novel photoelectrochemical DNA biosensor. CIPO (bis(2,4,5-trichlro-6-n-pentoxycarbonylphenyl)oxalate)-H(2)O(2) 9,10-diphenylanthrancene was selected as a CL system, which can produce appropriate exciting light and excite photoelectro active materials Ru(bpy)(2)dppz(2+) intercalated into the double-stranded DNA. Using such simple intercalation method, a detection limit of 4.5*10(-9) M target DNA was achieved without any amplification process. In addition, the selected CL system could be used to excite AuNPs-Ru(bpy)(2)dppz(2+) complex as well as CdSe QD multilayer, which indicated a good applicability for the established method. PMID- 21035322 TI - High-performance amperometric biosensors and biofuel cell based on chitosan strengthened cast thin films of chemically synthesized catecholamine polymers with glucose oxidase effectively entrapped. AB - Rapid oxidation of dopamine (DA) or L-noradrenaline (NA) by K(3)Fe(CN)(6) yields poly(DA) (PDA(C)) or poly(NA) (PNA(C)) with glucose oxidase (GOx) effectively entrapped, and such an enzyme-entrapped catecholamine polymer is cast on an Au electrode followed by chitosan (CS) strengthening for biosensing and fabrication of a biofuel cell (BFC). The optimized glucose biosensor of CS/PDA(C)-GOx/Au displays an extremely high sensitivity up to 135 MUA mM(-1) cm(-2), a very low limit of detection of 0.07 MUM, a response time of <3 s, good suppression of interferents, striking thermostability (lifetime of 3 weeks at 60 degrees C and over 2 months at 30 degrees C), and high resistance to urea denaturation. The biosensor also works well in the second generation biosensing mode with p benzoquinone (BQ) or ferrocene monocarboxylic acid (Fc) as an artificial mediator, with greatly broadened linear detection ranges (2.0 MUM-48.0 mM for BQ and 2.0 MUM-16.0 mM for Fc) and up to mA cm(-2)-scale glucose-saturated current density. The good permeability of artificial mediators across the enzyme film enables the quantification of the surface concentration of immobilized GOx on the basis of a reported kinetic model, and UV-Vis spectrophotometry is used to measure the enzymatic activity, revealing high enzymatic activity/load at CS/PDA(C)-GOx/Au. A BFC is also successfully fabricated with a bioanode of CS/PDA(C)-GOx/Au in phosphate buffer solution containing 100 mM glucose and 4.0 mM BQ and a carbon cathode in Nafion-membrane-isolated acidic KMnO(4), and its maximum power density of 1.62 mW cm(-2) is superior to those of most BFC hitherto reported. PMID- 21035323 TI - Sequential drug verification errors resulting in wrong drug administration during caesarean section. AB - An intravenous bolus of phentolamine was inadvertently given to a parturient during an emergency caesarean section following delivery of her infant when the intention had been to give an intravenous bolus of 5 IU Syntocinon. Root cause analysis identified a series of errors originating in the hospital pharmacy when one drug package was mistakenly issued in place of another. Subsequent checks failed to detect the original mistake. The final and most important check immediately before intravenous administration was also at fault. This case highlights a systems failure that permitted issue, transportation and administration of the wrong drug to a parturient. Robust measures to ensure avoidance of drug administration errors should be evaluated and introduced where possible. PMID- 21035324 TI - Sexual function and experience among long-term survivors of childhood cancer. AB - AIM: The objective was to compare sexual function, sexual experience and quality of partner relationship by gender in a cohort of long-term survivors of childhood cancer with a sample from the general population. METHODS: A 30-item self reported postal questionnaire was completed by a cohort of 224 (64%) long-term survivors of childhood cancer and 283 (51%) randomly selected persons from the general population. RESULTS: Male survivors more often reported periods of low sexual interest (p = 0.019), more frequently reported low sexual satisfaction (p = 0.015), less frequently reported feeling sexually attractive (p = 0.020) and reported a lower total number of sexual partners (p = 0.031) than males in the comparison group did. Males diagnosed with a central nervous system (CNS) tumour more frequently reported sexual arousal problems (p = 0.003), low sexual satisfaction (p = 0.021) and total number of sexual partners (p = 0.012) than did males with other diagnoses. There were no statistically significant differences regarding sexual function between the female survivors and the females in the comparison group. CONCLUSION: The results indicate that cancer disease and treatment have more impact on sexual function of male survivors than on the sexual function of female survivors. Amongst the survivors, males diagnosed with CNS tumours were shown to be the most vulnerable group. Assessment of sexual function is recommended to be included in regular follow-ups after childhood cancer. PMID- 21035325 TI - Phytotoxic and antifungal metabolites from Curvularia sp. FH01 isolated from the gut of Atractomorpha sinensis. AB - Two main phytotoxic and antifungal phthalic acid butyl isobutyl ester (1) and radicinin (2) were isolated from the culture of Curvularia sp. FH01, a fungus residing in the Atractomorpha sinensis gut. The structures of isolated metabolites were established on the basis of spectral analysis. Metabolites 1 and 2 exhibited significant phytotoxic activity against the radical growth of Echinochloa crusgalli with their IC(50) values of 61.9 and 5.9 MUg/mL, respectively, which were comparable to that 2,4-dichlorophenoxyacetic acid (2.0 MUg/mL) used as a positive control. The antifungal test results showed that compound 2 possessed strong antifungal activity against Magnaporthe grisea (IC(50)=16.3 MUg/mL) and Valsa mali (IC(50)=18.2 MUg/mL). The findings of the present study suggest that bioactive properties of the fungus FH01 can be attributed to its major components, phthalic acid butyl isobutyl ester and radicinin, and both agents have a potential to be used as herbicide and fungicide. PMID- 21035326 TI - Effect of anoxic/aerobic phase fraction on N2O emission in a sequencing batch reactor under low temperature. AB - Laboratory scale anoxic/aerobic sequencing batch reactor (A/O SBR) was operated around 15 degrees C to evaluate the effect of anoxic/aerobic phase fraction (PF) on N(2)O emission. The ammonia removal exhibited a decrease trend with the increase of PF, while the highest total nitrogen removal was achieved at PF=0.5. Almost all the N(2)O was emitted during the aerobic phase, despite of the PF value. However, the net emission of N(2)O was affected by PF. Under the premise of completely aerobic nitrification, the lowest N(2)O emission was achieved at PF=0.5, with a N(2)O-N conversion rate of 9.8%. At lower PF (PF=0.2), N(2)O emission was stimulated by residual nitrite caused by uncompleted denitrification during the anoxic phase. On the other hand, the exhaustion of the easily degradable carbon was the major cause for the high N(2)O emission at higher PF (PF=0.5). The N(2)O emission increased with the decreasing temperature. The time weighted N(2)O emission quantity at 15 degrees C was 2.9 times higher than that at 25 degrees C. PMID- 21035327 TI - Variation in Miscanthus chemical composition and implications for conversion by pyrolysis and thermo-chemical bio-refining for fuels and chemicals. AB - Different species and genotypes of Miscanthus were analysed to determine the influence of genotypic variation and harvest time on cell wall composition and the products which may be refined via pyrolysis. Wet chemical, thermo-gravimetric (TGA) and pyrolysis-gas chromatography-mass spectrometry (Py-GC-MS) methods were used to identify the main pyrolysis products and determine the extent to which genotypic differences in cell wall composition influence the range and yield of pyrolysis products. Significant genotypic variation in composition was identified between species and genotypes, and a clear relationship was observed between the biomass composition, yields of pyrolysis products, and the composition of the volatile fraction. Results indicated that genotypes other than the commercially cultivated Miscanthus x giganteus may have greater potential for use in bio refining of fuels and chemicals and several genotypes were identified as excellent candidates for the generation of genetic mapping families and the breeding of new genotypes with improved conversion quality characteristics. PMID- 21035328 TI - Treatment of waste gas from the breather vent of a vertical fixed roof p-xylene storage tank by a trickle-bed air biofilter. AB - This study applied a pilot-scale trickle-bed air biofilter (TBAB) system for treating waste gas emitted from the breather vent of a vertical fixed roof storage tank containing p-xylene (p-X) liquid. The volatile organic compound (VOC) concentration of the waste gas was related to ambient temperature as well as solar radiation, peaking at above 6300 ppmv of p-X and 25000 ppmv of total hydrocarbons during the hours of 8 AM to 3 PM. When the activated carbon adsorber was employed as a VOC buffer, the peak waste gas VOC concentration was significantly reduced resulting in a stably and efficiently performing TBAB system. The pressure drop appeared to be low, reflecting that the TBAB system could be employed in the prolonged operation with a low running penalty. These advantages suggest that the TBAB system is a cost-effective treatment technology for VOC emission from a fixed roof storage tank. PMID- 21035329 TI - Fatty acid derivatives and their use as CFPP additives in biodiesel. AB - One of the main drawbacks of the use of biodiesel is its bad behavior at low temperatures. In this work, we show that it is possible to take profit of the presence of free fatty acids in the starting materials used for biodiesel production (i.e. reused oils) by synthesizing additives able to improve cold flow properties. The synthesis of fatty acid derivatives have been successfully carried out by esterification of stearic, oleic and linoleic acids with bulky linear and cyclic alcohols and by epoxidation of methyl oleate and subsequent ring-opening reaction with the same alcohols. The study of crystallization patterns of pure derivatives by DSC and optical microscopy revealed the improvement of cold properties of biodiesel. Blends of biodiesel with up to 5% of some of these compounds allowed a decrease of CFPP (Cold Filter Pour Point). Both observations reveal the utility of these compounds as cheap and renewable additives. PMID- 21035330 TI - Expression and inducibility of endosulfan metabolizing gene in Rhodococcus strain isolated from earthworm gut microflora for its application in bioremediation. AB - The metabolizing potential of a bacterial strain Rhodococcus MTCC 6716, isolated from the gut of an Indian earthworm (Metaphire posthuma) was studied for endosulfan bioremediation. In the present work, the optimum conditions for the maximum growth, kinetic of endosulfan degradation, regression equation, half life and correlation coefficient were studied. Endosulfan induced alterations in the expression of mRNA and protein of specific endosulfan metabolizing marker gene (Esd) was studied. Maximum growth of bacteria was observed at pH 7.0, 30 degrees C and 0.085 M sodium chloride concentration in a liquid culture medium. Endosulfan was degraded by Rhodococcus strain up to 97.23% within 15 days without producing toxic metabolite and with strong correlation coefficient (-0.728) and half life 5.99 days. Endosulfan degradation was mediated through gene(s) present in genomic DNA. Expression of marker gene was found endosulfan concentration dependent. The results suggest that this novel strain (Rhodococcus) may be utilized for bioremediation of endosulfan. PMID- 21035331 TI - Identification and structure-activity relationship of 2-morpholino 6-(3 hydroxyphenyl) pyrimidines, a class of potent and selective PI3 kinase inhibitors. AB - PI3 Kinases are a family of lipid kinases mediating numerous cell processes such as proliferation, migration, and differentiation. The PI3 kinase pathway is often de-regulated in cancer through PI3Kalpha overexpression, gene amplification, mutations, and PTEN phosphatase deletion. PI3K inhibitors represent therefore an attractive therapeutic modality for cancer treatment. Herein we describe a novel series of PI3K inhibitors sharing a pyrimidine core and showing significant potency against class I PI3 kinases in the biochemical assay and in cells. The discovery, synthesis and SAR of this chemotype are described. PMID- 21035332 TI - Synthetic analogs of indole-containing natural products as inhibitors of sortase A and isocitrate lyase. AB - Guided by the inhibitory activities of indole-containing natural products against isocitrate lyase (ICL) from Candida albicans and sortase A (SrtA) from Staphylococcus aureus, a series of compounds structurally analogous to natural products were synthesized. Eight SrtA inhibitors and an ICL inhibitor having higher activities than the natural products were discovered by screening the enzyme inhibitory activities of synthesized compounds. Among the SrtA inhibitors discovered, six exhibited higher activities than p-hydroxymercuribenzoic acid, which suggests that these compounds have great potential as alternative antibacterial agents. PMID- 21035333 TI - Construction of a 'turn-on' fluorescent probe system for His-tagged proteins. AB - Hexahistidine ((His)(6)) tags are used to purify genetically engineered proteins. Herein, we describe the construction of a 'turn-on' fluorescent probe system that consists of the fluorescence quencher, Dabcyl, conjugated to (His)(6), and fluorescent tetramethylrhodamine conjugated to nitrilotriacetic acid, which, in the presence of Ni(2+), can bind (His)(6). The system is turned off when Dabcyl (His)(6) is bound to the fluorescent nitrilotriacetic acid derivative. The binding strength of this system was assessed using electrospray ionization mass spectrometry, fluorescence correlation spectroscopy, and fluorescence intensity distribution analysis-polarization. Although there was no significant enhancement in fluorescence after addition of an equimolar amount of ubiquitin, the fluorescence increased from 14% to 40% of its initial intensity when an equimolar amount of (His)(6)-ubiquitin was added. Therefore, this system should be able to specifically recognize (His)(6)-proteins with good resolution and has the additional advantage that a washing step is not required to remove fluorescent probe, that is, not bound to the (His)(6)-protein. PMID- 21035334 TI - Discovery and selectivity-profiling of 4-benzylamino 1-aza-9-oxafluorene derivatives as lead structures for IGF-1R inhibitors. AB - Recently the insuline-like growth factor receptor (IGF-1R) emerged as a promising target structure for the development of novel anti-cancer agents. IGF-1R plays a central role in both tumour progression and resistance development against anti cancer drugs. We discovered 1-aza-9-oxafluorene derivatives as novel lead structures with submicromolar activities against IGF-1R. Structure-activity relationships (SARs) on a series of related receptor tyrosine kinases (RTKs) are discussed in the context of available crystal structures. A preliminary selectivity-profiling is demonstrated for the first compound series. Antiproliferative tumour cell line screening studies yielded one candidate as a promising cytostatic agent without significant toxic effects. PMID- 21035335 TI - Synthesis, antimicrobial evaluation and QSAR studies of novel piperidin-4-yl-5 spiro-thiadiazoline derivatives. AB - In an attempt to find a new class of antimicrobial agents, a series of new 1,3,4 thiadiazolines were synthesized from 2,6-diarylpiperidin-4-ones, via the corresponding 4'-phenylthiosemicarbazones. All the synthesized compounds (23-39) were virtually screened against bacterial (Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Salmonella typhi) and fungal strains (Candida albicans, Rhizopus sp, Aspergillus niger and Aspergillus flavus) by serial dilution method. QSAR study indicated that the increase in weakly polar component of solvent accessible surface area will favour antibacterial activity while increase in polarizability and decrease in ionisation potential and hydrogen bond donor will favour antifungal activity. PMID- 21035336 TI - 5-amino-pyrazoles as potent and selective p38alpha inhibitors. AB - The synthesis and structure-activity relationships (SAR) of p38alpha MAP kinase inhibitors based on a 5-amino-pyrazole scaffold are described. These studies led to the identification of compound 2j as a potent and selective inhibitor of p38alpha MAP kinase with excellent cellular potency toward the inhibition of TNFalpha production. Compound 2j was highly efficacious in vivo in inhibiting TNFalpha production in an acute murine model of TNFalpha production. X-ray co crystallography of a 5-amino-pyrazole analog 2f bound to unphosphorylated p38alpha is also disclosed. PMID- 21035338 TI - Interaction of 3'-azido-3'-deamino daunorubicin with human serum albumin: investigation by fluorescence spectroscopy and molecular modeling methods. AB - In this Letter, the binding of 3'-azido-3'-deamino daunorubicin (ADNR) to human serum albumin (HSA) was investigated at different temperatures by fluorescence spectroscopy at pH 7.4. The binding constant was determined according to Stern Volmer equation based on the fluorescence quenching of HSA in the presence of ADNR. The thermodynamic parameters, DeltaH and DeltaS, were calculated according to the dependence of enthalpy change on the temperature to be -21.01 kJ mol(-1) and 24.71 J K(-l) mol(-l), respectively. The results revealed that ADNR had a strong ability to quench the intrinsic fluorescence of HSA through a static quenching procedure. The hydrophobic force played a major role in the interaction of ADNR with HSA, which was in good agreement with the results of molecular modeling study. The effect of various metal ions on the binding constants of ADNR with HSA was also investigated. All the experimental results and theoretical data indicated that ADNR could bind to HSA and be effectively transported and eliminated in body, which might be a useful guideline for further drug design. PMID- 21035337 TI - Discovery of N-benzyl-N'-(4-pipyridinyl)urea CCR5 antagonists as anti-HIV-1 agents (I): optimization of the amine portion. AB - Several series of carbamate, urea and carboxamide-based CCR5 antagonists have been discovered via optimizations at the amine portion of lead compound 2. All compounds were evaluated for their antiviral activities. Lead urea 29 showed good pharmacokinetic properties, justifying further development of this series. PMID- 21035339 TI - Design and synthesis of macrocyclic indoles targeting blood coagulation cascade Factor XIa. AB - The synthesis of a series of novel macrocyclic compounds designed to target blood coagulation Factor XIa is described. The compounds were evaluated for their inhibition of a small set of serine proteases. Several compounds displayed modest activity and good selectivity for Factor XIa. Within the series, a promising lead structure for developing novel macrocyclic inhibitors of thrombin was identified. PMID- 21035340 TI - The predictive value of suspicious sonographic characteristics in atypical cyst like breast lesions. AB - BACKGROUND AND PURPOSE: Simple breast cysts are a common sonographic finding and do not require further diagnostic evaluation. In contrast, atypical breast cysts do harbour a risk of malignancy. The purpose of this study was to evaluate the predictive value of sonographic findings that are considered characteristic of malignant atypical cyst-like lesions. PATIENTS AND METHODS: Six descriptive sonographic criteria of 202 atypical cysts in 176 women were compared with histopathological findings after surgical excision and their statistical association was evaluated. RESULTS: Of these six criteria thick cyst wall (p < 0.0001), lobulation (p = 0.0001) and hyperechogenicity (p = 0.003) were found to be highly predictive of breast cancer. The presence of two or more sonographic criteria was associated with a 10.3 times greater risk of malignancy (p < 0.0001). CONCLUSION: The association between suspicious sonographic criteria and histology after surgery was evaluated. We propose surgical excision when two or more sonographic criteria are diagnosed in a single atypical breast cyst. PMID- 21035341 TI - Reconstitution and protein composition analysis of endocytic actin patches. AB - BACKGROUND: Clathrin-actin-mediated endocytosis in yeast involves the progressive assembly of at least 60 different proteins at cortical sites. More than half of these proteins are involved in the assembly of a branched network of actin filaments to provide the forces required for plasma membrane invagination. RESULTS: To gain insights into the regulation of endocytic actin patch dynamics, we developed an in vitro actin assembly assay using microbeads functionalized with the nucleation promoting factor (NPF) Las17 (yeast WASP). When incubated in a yeast extract, these beads assembled actin networks, and a significant fraction became motile. Multidimensional protein identification technology (MudPIT) showed that the recruitment of actin-binding proteins to these Las17-derived actin networks is selective. None of the proteins known to exclusively regulate the in vivo formation of actin cables or the actin contractile ring were identified. Our analysis also identified components of three other cortical structures, eisosomes, phosphoinositide kinase (PIK) patches, and the TORC2 complex, establishing intriguing biochemical connections between four different yeast cortical complexes. Finally, we identified Aim3 as a regulator of actin dynamics at endocytic sites. CONCLUSIONS: WASP is sufficient to trigger assembly of actin networks composed selectively of actin patch proteins. These experiments establish that the protein composition of different F-actin structures is determined by the protein factor that initiates the network. The identification of binding partners revealed new biochemical connections between WASP-derived networks and other cortical complexes and identified Aim3 as a novel regulator of the endocytic actin patch. PMID- 21035342 TI - Rab-family GTPase regulates TOR complex 2 signaling in fission yeast. AB - BACKGROUND: From yeast to human, TOR (target of rapamycin) kinase plays pivotal roles in coupling extracellular stimuli to cell growth and metabolism. TOR kinase functions in two distinct protein complexes, TOR complex 1 (TORC1) and 2 (TORC2), which phosphorylate and activate different AGC-family protein kinases. TORC1 is controlled by the small GTPase Rheb, but little is known about TORC2 regulators. RESULTS: We have identified the Ryh1 GTPase, a human Rab6 ortholog, as an activator of TORC2 signaling in the fission yeast Schizosaccharomyces pombe. Mutational inactivation of Ryh1 or its guanine nucleotide exchange factor compromises the TORC2-dependent phosphorylation of the AGC-family Gad8 kinase. In addition, the effector domain of Ryh1 is important for its physical interaction with TORC2 and for stimulation of TORC2 signaling. Thus, GTP-bound Ryh1 is likely to be the active form stimulatory to TORC2-Gad8 signaling. Consistently, expression of the GTP-locked mutant Ryh1 is sufficient to promote interaction between TORC2 and Gad8 and to induce Gad8 hyperphosphorylation. The loss of functional Ryh1, TORC2, or Gad8 brings about similar vacuolar fragmentation and stress sensitivity, further corroborating their involvement in a common cellular process. Human Rab6 can substitute Ryh1 in S. pombe, and therefore Rab6 may be a potential activator of TORC2 in mammals. CONCLUSIONS: In its GTP-bound form, Ryh1, an evolutionarily conserved Rab GTPase, activates TORC2 signaling to the AGC kinase Gad8. The Ryh1 GTPase and the TORC2-Gad8 pathway are required for vacuolar integrity and cellular stress resistance in S. pombe. PMID- 21035343 TI - An evolutionarily conserved autoinhibitory molecular switch in ELMO proteins regulates Rac signaling. AB - Dedicator of cytokinesis (DOCK) proteins are guanine nucleotide exchange factors (GEFs) controlling the activity of Rac1/Cdc42 during migration, phagocytosis, and myoblast fusion [1-4]. Engulfment and cell motility (ELMO) proteins bind a subset of DOCK members and are emerging as critical regulators of Rac signaling [5-10]. Although formation of a DOCK180/ELMO complex is not essential for Rac1 activation, ELMO mutants deficient in binding to DOCK180 are unable to promote cytoskeleton remodeling [11]. How ELMO regulates signaling through DOCK GEFs is poorly understood. Here, we identify an autoinhibitory switch in ELMO presenting homology to a regulatory unit described for Dia formins. One part of the switch, composed of a Ras-binding domain (RBD) and Armadillo repeats, is positioned N terminally while the other is housed in the C terminus. We demonstrate interaction between these fragments, suggesting autoinhibition of ELMO. Using a bioluminescence resonance energy transfer biosensor, we establish that ELMO undergoes conformational changes upon disruption of autoinhibition. We found that engagement of ELMO to RhoG, or with DOCK180, promotes the relief of autoinhibition in ELMO. Functionally, we found that ELMO mutants with impaired autoregulatory activity promote cell elongation. These results demonstrate an unsuspected level of regulation for Rac1 signaling via autoinhibition of ELMO. PMID- 21035345 TI - Dissecting the immune response to the entomopathogen Photorhabdus. AB - Bacterial pathogens either hide from or modulate the host's immune response to ensure their survival. Photorhabdus is a potent insect pathogenic bacterium that uses entomopathogenic nematodes as vectors in a system that represents a useful tool for probing the molecular basis of immunity. During the course of infection, Photorhabdus multiplies rapidly within the insect, producing a range of toxins that inhibit phagocytosis of the invading bacteria and eventually kill the insect host. Photorhabdus bacteria have recently been established as a tool for investigating immune recognition and defense mechanisms in model hosts such as Manduca and Drosophila. Such studies pave the way for investigations of gene interactions between pathogen virulence factors and host immune genes, which ultimately could lead to an understanding of how some Photorhabdus species have made the leap to becoming human pathogens. PMID- 21035346 TI - Aspergillus nidulans asexual development: making the most of cellular modules. AB - Asexual development in Aspergillus nidulans begins in superficial hyphae as the programmed emergence of successive pseudohyphal modules, collectively known as the conidiophore, and is completed by a layer of specialized cells (phialides) giving rise to chains of aerial spores. A discrete number of regulatory factors present in hyphae play different stage-specific roles in pseudohyphal modules, depending on their cellular localization and protein-protein interactions. Their multiple roles include the timely activation of a sporulation-specific pathway that governs phialide and spore formation. Such functional versatility provides for a new outlook on morphogenetic change and the ways we should study it. PMID- 21035344 TI - Stem cell-based biological tooth repair and regeneration. AB - Teeth exhibit limited repair in response to damage, and dental pulp stem cells probably provide a source of cells to replace those damaged and to facilitate repair. Stem cells in other parts of the tooth, such as the periodontal ligament and growing roots, play more dynamic roles in tooth function and development. Dental stem cells can be obtained with ease, making them an attractive source of autologous stem cells for use in restoring vital pulp tissue removed because of infection, in regeneration of periodontal ligament lost in periodontal disease, and for generation of complete or partial tooth structures to form biological implants. As dental stem cells share properties with mesenchymal stem cells, there is also considerable interest in their wider potential to treat disorders involving mesenchymal (or indeed non-mesenchymal) cell derivatives, such as in Parkinson's disease. PMID- 21035347 TI - 1-Benzyl derivatives of 5-(arylamino)uracils as anti-HIV-1 and anti-EBV agents. AB - Pyrimidine analogs have long found use over a broad chemotherapeutic spectrum. In an effort to further explore the antiviral potential of several uracil derivatives previously synthesized in our laboratories, a series of benzylated pyrimidines were designed and synthesized. Introduction of the benzyl residue onto the 5-phenylaminouracil scaffold was carried out using 2,4 bis(trimethylsilyloxy)pyrimidine with the corresponding benzyl bromides. Similarly, 1-benzyl-5-(benzylamino)- and 1-benzyl-5-(phenethylamino)uracils were obtained via amination of 1-benzyl-5-bromouracils with benzylamine or phenylethylamine. The results of the broad screen antiviral studies revealed that compounds 5 and 11 exhibit promising inhibitory activity against HIV-1 in CEM-SS culture. A 50% protective effect was observed at concentrations of 11.9 and 9.5 MUM, respectively. Moreover, compounds 8 and 3 exhibited good inhibitory effects against EBV in AKATA cell culture with EC50 values of 2.3 and 12 MUM, respectively. The synthesis and biological studies are detailed herein. PMID- 21035348 TI - N6-Alkyladenosines: Synthesis and evaluation of in vitro anticancer activity. AB - A series of adenosine analogues differently substituted in N6-position were synthesized to continue our studies on the relationships between structure and biological activity of iPA. The structures of the compounds were confirmed by standard studies of 1H NMR, MS and elemental analysis. These molecules were then evaluated for their anti-proliferative activity on bladder cancer cells. We found that some of these compounds possess anti-proliferative activity but have no effect on cell invasion and metalloprotease activity. PMID- 21035349 TI - Zinc-finger hydrolase: Computational selection of a linker and a sequence towards metal activation with a synthetic alphabetabeta protein. AB - The zinc-finger protein is targeted for computational redesign as a hydrolase enzyme. Successful in having zinc activated for hydrolase function, the study validates the stepwise approach to having the protein tuned in main-chain structure stereochemically and over side chains chemically. A leucine homopolypeptide, harboring histidines to tri coordinate zinc and d-amino-acid nucleated alpha-helix and beta-hairpin building blocks of an alphabetabeta protein, is taken up for modeling, first with cyana, in a mixed-chirality linker between the building blocks, and then with IDeAS, in a sequence over side chains. The designed mixed-chirality polypeptide structure is proven to order as an intended alphabetabeta fold and capture zinc to activate its role as a hydrolase catalyst. The design approach to have protein folds defined stereochemically and receptor and catalysis functions defined chemically is presented, and illustrates L- and D-alpha-amino-acid structures as the alphabet integrating chemical- and stereochemical-structure variables as its letters. PMID- 21035350 TI - Epidemiology in a Mediterranean region of cardiac surgery patients in the 21st century. PMID- 21035351 TI - Photodynamic therapy using topically applied hypericin: comparative effect with methyl-aminolevulinic acid on UV induced skin tumours. AB - Photodynamic therapy (PDT) is a treatment option particularly well-suited for superficial (pre)malignant skin lesions due to the skin's accessibility to light. In the present study, the efficacy of topical hypericin-PDT was evaluated using a mouse model for actinic keratosis. For comparison, similar experiments were conducted with methyl-aminolevulinic acid (Me-ALA). Small skin tumours (1-2 mm) were induced in hairless mice by chronic UV irradiation. After topical application of hypericin (0.1% in gelcream for 24 h) or Me-ALA (Metvix(r) for 4 h), the lesional/non-lesional skin surface fluorescence ratio was determined and fluorescence microscopy was used to study the skin penetration of the photosensitizers. The antitumour activity of topical PDT (20 mW cm(-2), 40 J cm( 2)) was evaluated by measurement of the lesional diameters. Moreover, biopsies were taken at various time points after PDT for histological evaluation of the therapy. Our results demonstrate that after topical application of hypericin and Me-ALA, tumour selectivity is limited in mouse skin. The microscopic distribution of hypericin fluorescence showed an accumulation in the stratum corneum and low fluorescence levels in the rest of the lesions, whereas the distribution of PpIX in the skin was more homogenous. Topical hypericin-PDT was found to be less efficient (44% total lesional clearance) as compared to Me-ALA-PDT (80% total lesional clearance). Full lesional necrosis was observed in responsive lesions, and the atypical cells of actinic keratosis were replaced by normal keratinocytes 3 weeks later, both after hypericin-PDT and Me-ALA-PDT. PMID- 21035352 TI - Impact of liposomal doxorubicin-based adjuvant chemotherapy on autonomy in women over 70 with hormone-receptor-negative breast carcinoma: A French Geriatric Oncology Group (GERICO) phase II multicentre trial. AB - RATIONALE: Breast cancer is a disease of ageing. Functional independence in elderly patients, measured with the Katz activities of daily living (ADL) scale, predicts overall survival and the need for welfare support. Few prospective studies have examined the feasibility of adjuvant chemotherapy and its impact on autonomy in women over 70 years of age with high-risk breast cancer. This multicentre phase II trial was designed to assess the impact of adjuvant anthracycline-based chemotherapy on these patients' autonomy. DESIGN AND METHODS: In a two-stage Fleming design, women aged >=70 years with histologically proven hormone-receptor-negative early breast cancer and a significant risk of recurrence (pN+ or "high risk" pN0) received 4 cycles of nonpegylated liposomal doxorubicin 60 mg/m(2) and cyclophosphamide 600 mg/m(2) every 3 weeks postoperatively, on an outpatient basis. The primary endpoint was the change in the ADL score during chemotherapy. Secondary endpoints include comprehensive geriatric, quality-of-life and acceptability assessments, tolerability, and long term outcome. The results for the primary endpoint and other scales at completion of adjuvant chemotherapy are reported here, while long-term follow-up is not yet complete. RESULTS: Forty patients (median age 75 [70-82]) were enrolled between February 2006 and November 2007. Chemotherapy had no deleterious impact on ADL, cognition, mental status, or the frequency of comorbidities. In contrast, the number of patients at risk of malnutrition, based on the Mini Nutritional Assessment, more than doubled between baseline and the end of chemotherapy, rising from 15% to 38%. Quality-of-life deteriorated in terms of social and role functioning, likely owing to fatigue, loss of appetite, nausea and vomiting. Treatment acceptability was good. The main adverse effect was neutropenia, 15% of the patients experiencing febrile neutropenia. No cardiac toxicity or toxic deaths occurred. CONCLUSION: This study demonstrates the feasibility of an adjuvant chemotherapy regimen combining nonpegylated liposomal doxorubicin and cyclophosphamide in fit elderly women <85 years with breast cancer. Although chemotherapy had an impact on social and role functioning, autonomy was not impaired and toxicity was acceptable. Special attention should be paid to nutritional status before and after treatment. PMID- 21035353 TI - Imaging of malignant neoplasms of the mesenteric small bowel: new trends and perspectives. AB - This article describes the recent advances in radiological imaging of malignant neoplasms of the mesenteric small bowel and provides an outline of new trends and perspectives that can be anticipated. The introduction of multidetector row technology, which allows the acquisition of submillimeter and isotropic voxels, has dramatically improved the capabilities of computed tomography in the investigation of the mesenteric small bowel. This technology combined with optimal filling of small bowel loops through the use of appropriate enteral contrast agents has markedly changed small bowel imaging. Computed tomography enteroclysis, which is based on direct infusion of enteral contrast agent into the mesenteric small bowel through a naso-jejunal tube, provides optimal luminal distension. By contrast, computed tomography-enterography is based on oral administration of enteral contrast agent. These two techniques are now well established ones for the detection and the characterization of small bowel neoplasms. During the same time, combining the advantages of unsurpassed soft tissue contrast and lack of ionizing radiation, magnetic resonance imaging has gained wide acceptance for the evaluation of patients with suspected small bowel neoplasms. Rapid magnetic resonance imaging sequences used in combination with specific enteral contrast agents generate superb images of the mesenteric small bowel so that magnetic resonance-enteroclysis and magnetic resonance-enterography are now considered as effective diagnostic tools for both the detection and the characterization of neoplasms of the mesenteric small bowel. Recent improvements in image post-processing capabilities help obtain realistic three-dimensional representations of tumors and virtual enteroscopic views of the small bowel that are useful for the surgeon and the gastroenteroenteologist to plan surgical or endoscopic interventions. Along with a better knowledge of the potential and limitations of wireless capsule endoscopy and new endoscopic techniques, these recent developments in radiological imaging reasonably suggest that substantial changes in the investigation of small bowel tumors may be anticipated in a near future, thus potentially create a new paradigm shift after standard small bowel follow-through study has been universally abandoned. PMID- 21035354 TI - VEGF targeted therapy in acute myeloid leukemia. AB - The cooperation of two classes of mutations in hematopoietic cells is hypothesized in a multistep pathogenesis model of acute myeloid leukemia (AML). Class I mutations confer a proliferative and/or survival advantage, whereas Class II mutations block hematopoietic differentiation and impair apoptosis in AML cells. In addition to these two classes of mutations, a relevant role for angiogenesis in the pathophysiology of AML has been recently proposed. The recognition that the vascular endothelial growth factor (VEGF) pathway is a key regulator of angiogenesis has led to the development of several VEGF-targeted approaches. These include neutralizing antibodies, VEGF traps or selective tyrosine kinase inhibitors for VEGFRs. Other drugs that indirectly affect VEGF pathway, such as statins or arsenic trioxide, also have been shown to possess antiangiogenic activity in leukemias. The benefits of these VEGF targeted agents and their current stage of development as novel anti-antiangiogenic therapies in AML are discussed in this review. PMID- 21035355 TI - The role of cytokines and chemokines in severe respiratory syncytial virus infection and subsequent asthma. AB - Respiratory syncytial virus (RSV) is the primary cause of serious lower respiratory tract illness in infants and young children worldwide. The mechanism is largely unknown. RSV stimulates airway epithelial cells and resident leukocytes to release cytokines. Cytokines and chemokines involved in host response to RSV infection are thought to play a central role in the pathogenesis. In addition, RSV infection early in life has been associated with the development of asthma in later childhood. It is likely that the persistence of cytokines and chemokines in fully recovered patients with RSV in the long term can provide a substratum for the development of subsequent asthma. This review describes the genetic factors in cytokines and chemokines associated with severity of RSV disease, cytokines and chemokines synthesis in RSV infection, and the role of these innate immune components in RSV-associated asthma. PMID- 21035356 TI - Improving inferior vena cava filter retrieval rates: impact of a dedicated inferior vena cava filter clinic. AB - PURPOSE: To test the hypothesis that an inferior vena cava (IVC) filter clinic increases the retrieval rate of optional IVC filters. MATERIALS AND METHODS: Patients who had optional IVC filters placed at the authors' institution between January 2000 and December 2008 were identified and retrospectively studied. A dedicated IVC filter clinic was established at this institution in January 2009, and there is a comprehensive database of prospectively acquired data for patients seen in the IVC filter clinic. Patients were chronologically classified into preclinic and postclinic groups. The number of optional filters retrieved and failed retrieval attempts were recorded. RESULTS: In the preclinic and postclinic periods, 369 and 100 optional IVC filters were placed. Median (interquartile range) number of optional filters placed per month for preclinic and postclinic periods was 3 (range 2-5) and 10 (range 6.5-10.5) (P < .001). Retrieval rates in preclinic and postclinic periods were 108 of 369 (29%) and 60 of 100 (60%) (P < .001). The median time to filter retrieval in the postclinic group was 1.5 months (95% confidence interval 1.2-1.8). The number of failed retrieval attempts in preclinic and postclinic periods was 23 of 369 (6%) and 5 of 100 (5%) (P = .823). CONCLUSIONS: The retrieval rate of optional IVC filters at this institution was significantly increased by the establishment of a dedicated IVC filter clinic. This retrieval increase is not related to a decrease in technical failures but more likely relates to more meticulous patient management and clinical follow-up. PMID- 21035357 TI - Treatment of postoperative hemorrhage with venous embolization. PMID- 21035358 TI - Efficacy and tolerability of long-term treatment with vagus nerve stimulation in adolescents and adults with refractory epilepsy and learning disabilities. AB - The long-term effects of vagus nerve stimulation (VNS) on seizure frequency were studied in 50 patients with epilepsy and learning disabilities. Mean observation time was 4.6 years. At follow-up, none of the patients was seizure-free, 25% had more than 50% seizure reduction, and 46% had some seizure reduction, but less than 50%. The discontinuation rate was 18%. Our results indicate that, like antiepileptic drugs, VNS does not have such a good seizure-reducing effect in patients with epilepsy and learning disabilities compared with the general epilepsy population. PMID- 21035360 TI - Molecular identification of the novel Ggamma-beta hybrid hemoglobin: Hb Ggamma beta Ulsan (Ggamma through 13; beta from 19). AB - Gene fusion is a very rare mechanism that produces hemoglobin variants. Less than ten types of beta-like hybrid globins have been reported to date. Herein we identified the first hybrid hemoglobin between Ggamma- and beta-globins in a five year-old Korean male who had thalassemia minor feature and triplication of the HBA2 gene (alphaalpha/alphaalphaalphaalpha). The novel globin originated from a 27,707-base pair deletion spanning from the HBG2 to HBB gene (NG_000007.3:g.42947_70653del). Its protein sequence included 13 N-terminal amino acids from Ggamma-globin, five common amino acids from Ggamma- and beta-globins, and 128 amino acids from beta-globin (Ggamma through 13; beta from 19). Molecular genetic analyses characterized the hybrid DNA and RNA. Mass spectrometry and de novo protein sequencing successfully identified the fusion peptide in the hybrid hemoglobin. We named this novel hybrid Hb Ggamma-beta Ulsan. The novel hemoglobin constituted 37.0% of the total hemoglobin and showed reduced oxygen affinity. PMID- 21035359 TI - Zebrafish von Willebrand factor. AB - von Willebrand factor (vWF) is a large protein involved in primary hemostasis. A dysfunction in this protein or an insufficient production of the protein leads to improper platelet adhesion/aggregation, resulting in a bleeding phenotype known as von Willebrand disease (vWD). To gain a better understanding of vWF interactions in vivo, the use of zebrafish as a model is ideal because of the transparency of the embryos and larvae. In this article, we examined the presence and function of vWF in hemostasis of zebrafish utilizing a variety of molecular methods. Using RT-PCR and antibody staining, we have shown that vWF mRNA is present in thrombocytes. Through antibody staining, we demonstrated vWF is synthesized in blood vessels. The role of zebrafish vWF in hemostasis was established through knockdown methods using vWF morpholino (vWF MO) antisense oligonucleotides. Embryos injected with vWF MO at the one to four cell stages resulted in a bleeding phenotype. Injection of embryos with vWF MO also caused an increase in time to occlusion within arteries in larvae upon laser induced injury. We then used vWF-specific Vivo-morpholinos (VMO) to induce vWF knockdown in adult zebrafish by targeting the exon homologous to the human exon 28 of the vWF gene. The reduced ristocetin-mediated agglutination of thrombocytes in a plate tilting assay, using blood from adult zebrafish injected with VMO, provided evidence that vWF is involved in the hemostatic process. We also administered desmopressin acetate to larvae and adults which resulted in enhanced aggregation/agglutination of thrombocytes. Zebrafish genome database analysis revealed the presence of GPIbbeta gene. It also revealed the exon of zebrafish vWF gene corresponding to exon 28 of human vWF gene is highly similar to the exon 28 of human vWF gene, except that it has an insertion that leads to a translated peptide sequence that separates the two A domains coded by this exon. This exon is also conserved in other fishes. In summary, we established that zebrafish vWF has a role similar to that of vWF found in humans, thus, making zebrafish a useful model for studying the cell biology of vWF in vivo. PMID- 21035361 TI - Prolonged activated prothromboplastin time and breed specific variation in haemostatic analytes in healthy adult Bernese Mountain dogs. AB - Coagulation tests are often performed in dogs suspected of haemostatic dysfunction and are interpreted according to validated laboratory reference intervals (RIs). Breed specific RIs for haematological and biochemical analytes have previously been identified in Bernese Mountain dogs, but it remains to be determined if breed specific RIs are necessary for haemostasis tests. Activated prothromboplastin time (aPTT), prothrombin time (PT), selected coagulation factors, D-dimers, fibrinogen, von Willebrand factor and thromboelastography (TEG) were analyzed in healthy Bernese Mountain dogs using the CLSI model. Three analytes (aPTT, TEG [MA] and TEG [G]) were different according to the CLSI model. For aPTT the new RI was markedly different (0-100s). Whereas the new intervals for TEG (MA) and TEG (G) may be due to breed related biological variation, the cause of the prolonged RI for aPTT is at present uncertain. PMID- 21035362 TI - Oral ketoprofen is effective in the treatment of non-infectious lameness in sows. AB - The efficacy of ketoprofen in the treatment of non-infectious lameness in sows was examined in a double-blinded study. Two dose rates of oral ketoprofen were compared to placebo treatment over five consecutive days. Lameness was assessed with a five-grade scoring system prior to and on the last day of the treatment. The rate of treatment success was 54.3% for the ketoprofen 4mg/kg group (n=46), 53.2% for the ketoprofen 2mg/kg group (n=47) and 20.8% for the pigs in the placebo group (n=48). The difference between both ketoprofen groups and the placebo group was significant (P=0.001), but there was no difference between the two ketoprofen groups (P=0.78). Oral ketoprofen was well tolerated and no adverse events were observed. As lameness is a very common problem in sows, oral ketoprofen appeared to be a practical way to alleviate pain and improve the welfare of sows. PMID- 21035363 TI - Real-time PCR and typing of Clostridium difficile isolates colonizing mare-foal pairs. AB - Clostridium difficile infection can occur in the dams of sick foals, but it is unknown if mares and foals share the same isolates. In this study, C. difficile isolates from fecal samples of 11 mares paired with 11 foals were genotyped by arbitrarily primed PCR; two mares and three foals in five mare-foal pairs had diarrhea. Fecal immunoassays were utilized to detect C. difficile common antigen and toxin A. Quantitative real-time PCR (qPCR) systems were developed to detect genes for toxins A and B, as well as for binary toxin B. Sequences of all toxins were present in all isolates, although only one horse was positive for toxin A on fecal immunoassay. Identical strains of C. difficile were present in 4/11 (36.4%) mare-foal pairs. Mare-foal pairs can harbor C. difficile subclinically and are potential reservoirs for colonization of each other. PMID- 21035364 TI - A psychophysical study of endogenous analgesia: the role of the conditioning pain in the induction and magnitude of conditioned pain modulation. AB - Endogenous analgesia (EA) can be examined experimentally using a conditioned pain modulation (CPM) paradigm. While noxious conditioning stimulation intensities (CSIs) are mainly used, it has not been fully investigated in the same experimental design whether the experienced conditioning pain level affects CPM responses. The principal goal of the present study was to characterize CPM induction and magnitudes evoked by various conditioning pain levels. Furthermore, we explored associations between conditioning pain reports and CPM responses across various CSIs. Thirty healthy, young, right-handed males were tested with a parallel CPM paradigm. Three different CSIs (hand water-immersion) induced mild, moderate and intense pain levels, rated 12.41 +/- 7.85, 31.57 +/- 9.56 and 58.1 +/- 11.43, respectively (0-100 numerical pain scale) (P < 0.0001). Contact-heat 'test-stimulus' levels were compared before and during conditioning. Within the group, (i) CPM was induced only by the moderate and intense CSIs (Ps <= 0.001); (ii) no difference was demonstrated between the magnitudes of these CPM responses. Regression analysis revealed that CPM induction was independent of the perceived conditioning pain level, but associated with the absolute CSI (P < 0.0001). Conditioning pain levels were correlated across all CSIs, as were CPM magnitudes (Ps <= 0.01). We conclude that among males, (i) once a CPM response is evoked by a required conditioning pain experience, its magnitude is not further affected by increasing conditioning pain and (ii) CPM magnitudes are inter correlated, but unrelated to conditioning pain reports. These observations may suggest that CPM responses represent an intrinsic element of an individual's EA processes, which are not significantly affected by the experienced conditioning pain. PMID- 21035365 TI - The displacement correlation tensor: microstructure, ensemble anisotropy and curving fibers. AB - Experiments with multiple diffusion wave vectors are known to carry more information than what is available from standard diffusion experiments. Here we consider a special case of this class of pulse sequences, the double wave vector diffusion experiment, and use the cumulant expansion of the signal to introduce the displacement correlation tensor. We discuss its physical interpretation and properties, noting in particular that its short time behavior allows determination of the surface to volume ratio of the pore space. We present a general expression for the displacement correlation tensor, and provide explicit expressions for a few model geometries. We then show that the scatter matrix characterizing the orientation distribution of an ensemble of cylinders is simply related to the displacement correlation tensor. This result is generalized to ensembles of pores with arbitrary shapes allowing a precise formulation of the influence of microstructural and ensemble anisotropy on the double wave vector diffusion signal in the Gaussian phase approximation. Finally, as a new application of the double wave vector diffusion signal, we analyze its behavior in a curving fiber, and suggest that the displacement correlation tensor may be used to estimate sub-voxel fiber curvature and deflection angle. The theoretical results are corroborated by computer simulations. PMID- 21035366 TI - Very fast magic angle spinning (1)H-(14)N 2D solid-state NMR: sub-micro-liter sample data collection in a few minutes. AB - Substantial resolution and sensitivity enhancements of solid-state (1)H detected (14)N HMQC NMR spectra at very fast MAS rates up to 80 kHz, in a 1mm MAS rotor, are presented. Very fast MAS enhances the (1)H transverse relaxation time and efficiently decouples the (1)H-(14)N interactions, both effects leading to resolution enhancement. The micro-coil contributes to the sensitivity increase via strong (14)N rf fields and high sensitivity per unit volume. (1)H-(14)N HMQC 2D spectra of glycine and glycyl-L-alanine at 70 kHz MAS at 11.7 T are observed in a few minutes with a sample volume of 0.8 MUL. PMID- 21035367 TI - Insights into the folding pathway of the Engrailed Homeodomain protein using replica exchange molecular dynamics simulations. AB - Protein folding studies were carried out by performing microsecond time scale simulations on the ultrafast/fast folding protein Engrailed Homeodomain (EnHD) from Drosophila melanogaster. It is a three-helix bundle protein consisting of 54 residues (PDB ID: 1ENH). The positions of the helices are 8-20 (Helix I), 26-36 (Helix II) and 40-53 (Helix III). The second and third helices together form a Helix-Turn-Helix (HTH) motif which belongs to the family of DNA binding proteins. The molecular dynamics (MD) simulations were performed using replica exchange molecular dynamics (REMD). REMD is a method that involves simulating a protein at different temperatures and performing exchanges at regular time intervals. These exchanges were accepted or rejected based on the Metropolis criterion. REMD was performed using the AMBER FF03 force field with the generalised Born solvation model for the temperature range 286-373 K involving 30 replicas. The extended conformation of the protein was used as the starting structure. A simulation of 600 ns per replica was performed resulting in an overall simulation time of 18 MUs. The protein was seen to fold close to the native state with backbone root mean square deviation (RMSD) of 3.16 A. In this low RMSD structure, the Helix I was partially formed with a backbone RMSD of 3.37 A while HTH motif had an RMSD of 1.81 A. Analysis suggests that EnHD folds to its native structure via an intermediate in which the HTH motif is formed. The secondary structure development occurs first followed by tertiary packing. The results were in good agreement with the experimental findings. PMID- 21035368 TI - Unrelated umbilical cord blood transplant for juvenile metachromatic leukodystrophy: a 5-year follow-up in three affected siblings. AB - Unrelated umbilical cord blood transplantation (UCBT) was used to treat three siblings with juvenile metachromatic leukodystrophy (jMLD). The efficacy of this therapy was measured over a 5-year period with serial neurological examinations, neuroimaging, nerve conduction studies (NCS), and neuropsychological evaluations (NPE). Outcomes were a function of disease stage at time of UCBT with alteration of disease course occurring in the first 2 years after UCBT and then subsequent halting of progression and stabilization of symptoms and disease. PMID- 21035369 TI - Routine use of CANTAB system for detection of neuropsychological deficits in patients with PKU. AB - Several studies have reported neuropsychological deficits related to hyper phenylalaninemia in patients with phenylketonuria (PKU). As computerized neuropsychological tests seem to be promising in the detection of such abnormalities, we aimed to assess the usefulness of routine use of CANTAB system in PKU clinic. A group of 49 PKU patients aged >16 years were tested by means of computerized CANTAB tests measuring speed of response, response inhibition, sustained attention, and working memory capacity. The scores achieved by study participants were analyzed with respect to their blood phenylalanine concentrations. Proper dietary control was observed in 22 patients, whereas in the remaining 27 persons, blood phenylalanine concentrations exceeded the recommended range. The results of the tests assessing sustained attention, working memory, and inhibitory control achieved by the non-compliant patients were significantly worse in comparison with patients maintaining proper diet. However, the mean scores achieved by treatment-adherent patients were also worse than expected, what could probably be related to problems with early start of treatment during their infancy. Our results confirmed the presence of specific neuropsychological deficits related to hyperphenylalaninemia in adults and adolescents with PKU. In our opinion, routine use of computerized neuropsychological tests should be recommended in PKU clinics. PMID- 21035371 TI - A pre-clinical phantom comparison of tissue harmonic and brightness mode imaging for application in ultrasound guided prostate brachytherapy. AB - PURPOSE: The current practice of prostate brachytherapy utilizes the brightness (B) mode ultrasound imaging for volume definition and needle guidance. However, tissue harmonic (H) mode available with new scanners has shown the improved image quality. The aim of this study was to perform a pre-clinical phantom evaluation of harmonic imaging as an alternative to B mode in prostate brachytherapy. METHODS: Performance characteristics viz. dead zone, depth of penetration, geometric accuracy, spatial resolution, tissue to clutter ratio (TCR) and signal to noise ratio (SNR), were compared between two modes using an in-house phantom. Images were acquired under the same settings except the gain; which is higher for the H mode than that of B mode. A qualitative comparison between two modes was also performed using commercial CIRS053 phantom. RESULTS: Dead zone, depth of penetration and geometric accuracy were respectively <1 mm, >8 cm and <1% for both modes. Relative TCR, SNR and the spatial resolution were improved in H mode compared with B mode. Images with CIRS053 phantom in H mode demonstrate sharper boundaries for prostate and urethra, freedom from background clutter, and better identification of the brachytherapy needles. CONCLUSIONS: This study indicates the superiority of H over B mode, in terms of spatial resolution, relative contrast, and overall image quality. Thus H mode has the potential benefit in prostate brachytherapy. This study provides the basis to move forward to investigate whether the superior image quality observed in the laboratory can be translated into a higher treatment quality for the patient. PMID- 21035370 TI - Regulation of the histone H4 monomethylase PR-Set7 by CRL4(Cdt2)-mediated PCNA dependent degradation during DNA damage. AB - The histone methyltransferase PR-Set7/Set8 is the sole enzyme that catalyzes monomethylation of histone H4 at K20 (H4K20me1). Previous reports document disparate evidence regarding PR-Set7 expression during the cell cycle, the biological relevance of PR-Set7 interaction with PCNA, and its role in the cell. We find that PR-Set7 is indeed undetectable during S phase and instead is detected during late G2, mitosis, and early G1. PR-Set7 is transiently recruited to laser-induced DNA damage sites through its interaction with PCNA, after which 53BP1 is recruited dependent on PR-Set7 catalytic activity. During the DNA damage response, PR-Set7 interaction with PCNA through a specialized "PIP degron" domain targets it for PCNA-coupled CRL4(Cdt2)-dependent proteolysis. PR-Set7 mutant in its "PIP degron" is now detectable during S phase, during which the mutant protein accumulates. Outside the chromatin context, Skp2 promotes PR-Set7 degradation as well. These findings demonstrate a stringent spatiotemporal control of PR-Set7 that is essential for preserving the genomic integrity of mammalian cells. PMID- 21035372 TI - [Aetiology and prognosis of prenatally diagnosed megacystis regarding gestational age at discovery. A six-year retrospective study]. AB - OBJECTIVES: The purpose of this study is to describe the diagnosis, the care and the prognosis of the fetuses with an antenataly diagnosed megacystis. PATIENTS AND METHODS: Six year retrospective study about 46 cases of megacystis (26 diagnosed during 1st trimester; 14 during 2nd trimester; 9 during 3rd trimester) referred in the prenatal fetal medicine unit of the Femme-Mere-Enfant hospital in Lyon (France). RESULTS: The main aetiology is urethral occlusion, particularly for megacystis discovered during the 1st and the 2nd trimesters. Twenty-two terminations of pregnancy were performed (47.8%) and 6 pregnancies arrested spontaneously (13%). Eighteen children were born alive, but 2 died in neonatal period. Finally, 16 children survived (34.8%). Chromosomal abnormalities are frequent (22%). DISCUSSION AND CONCLUSION: Antenatal discovery of a megacystis is a complex situation, and often of poor fetal prognosis. It requires a multidisciplinary approach to allow the concerned couple to be determined on the best care of this pregnancy. PMID- 21035373 TI - DNA profiling in blood, buccal swabs and hair follicles of patients after allogeneic peripheral blood stem cells transplantation. AB - To investigate the possibility that buccal swab and hair follicle samples could be used to detect recipients' personal identification or kinship study in forensic cases, who have received allogeneic peripheral blood stem cells transplantation (allo-PBSCT). Seven casework examples of materials collected from individuals after allo-PBSCT and their donors were investigated. Detection of genotypes was preformed by PCR analysis of short tandem repeats (STRs) in blood, buccal swab and hair follicle samples. Donor genotypes were detected in all blood samples of the patients. Case 2 recipient presented obvious chimeric DNA patterns (54% donor) and case 3 showed almost donor genotype (90% donor) in buccal swab samples. Other cases exhibited much lower chimeric DNA patterns in some alleles (from 2-16% donor). The average time after allo-PBSCT in case 2 and 3 recipients (123 months) was much longer than that of others (11 months). All of 7 recipients did not show donor-derived DNA patterns in hair samples. Therefore, this study suggests that sometimes buccal swab contains DNA from donor and yet hair follicle is a better source of personal identification or kinship study of recipients. PMID- 21035374 TI - Distribution of 42-bp variable tandem repeat polymorphism of the cold-induced autoinflammatory syndrome 1 (CIAS1) gene in eight human populations. AB - We recently identified a 42bp Variable Number of Tandem Repeats polymorphism in intron 4 of Cold-induced autoinflammatory syndrome 1 gene (CIAS1 42bp-VNTR), which are associated with CIAS1 gene expression and some inflammatory disease. The aim of our study is to investigate whether variability of CIAS1 42bp-VNTR allele is difference among races. A total of 1291 subjects from 7 populations (178 Chinese, 95 Korean, 614 Mongolian, 49 Bangladesh, 72 Sri Lanka, 192 African and 91 European) was genotyped on CIAS1 42bp-VNTR polymorphism, which was also compared to previous genotyping data from 508 Japanese subjects. A total of 11 genotypes and 5 alleles were found in 8 populations. The range of allele frequencies of CIAS1*6, CIAS1*7, CIAS1*9, CIAS1*12, and CIAS1*13 were 0.000 0.167, 0.056-0.248, 0.008-0.203, 0.570-0.923, and 0.000-0.104 in eight populations. The CIAS1*12 was the most common allele among all populations. The longest allele CIAS1*13 in African population was extremely high frequent at 0.104 compared to other population. While shortest allele CIAS1*6 was not observed Sri Lankan and African. Frequency (0.924) in the Sri Lankan population. These results showed that the CIAS1 42bp-VNTR polymorphism could represent genetic diversity among different human populations. PMID- 21035375 TI - Optimization of the ultrasound-assisted synthesis of allyl 1-naphthyl ether using response surface methodology. AB - Allyl 1-naphthyl ethers are useful compounds for different purposes, but reported methods to synthesize them require long reaction times. In this work, we have obtained allyl 1-naphthyl ether in good yield using ultrasonic-assisted methodology in a 1-h reaction. A central composite design was used to obtain a statistical model and a response surface (p<0.05; R(2)=0.970; R(2)(adj)=0.949; R(2)(pred)=0.818) that can predict the optimal conditions to maximize the yield, validated experimentally. PMID- 21035376 TI - Engineering the nanoparticle-protein interface: applications and possibilities. AB - Covalent and non-covalent conjugation of proteins to nanoparticles provides access to functional hybrid systems with applications in biotechnology, medicine, and catalysis. The creation of effective conjugates requires the retention of protein structure and function, a challenging task. In this review we discuss successes, challenges and opportunities in the area of protein-nanoparticle bioconjugation. PMID- 21035378 TI - Multi-wavelength spectrophotometric determination of the protolytic constants of tetracycline hydrochloride in some nonaqueous-water mixed solvents: a solvatochromism study. AB - Annihilation of the contribution of one chemical component from the original data matrix is a general method in rank annihilation factor analysis (RAFA). However, RAFA is not applicable for studying the protonation equilibria of multiprotic acids but in this study two-rank annihilation factor analysis (TRAFA) was used as an efficient chemometrics algorithm for determination of the protolytic constants (pKa) of tetracycline hydrochloride (TCHC) in some nonaqueous-water mixed solvents such as acetonitrile (AN)-water and methanol (MeOH)-water from the spectral pH-absorbance data. The spectral data was obtained from spectrophotometric acid-base titrations of different solutions of TCHC at (25.0+/ 0.10) degrees C and an ionic strength of 0.10 M. In TRAFA algorithm the pKa values were obtained with relationship between residual standard deviation (R.S.D.) and hypothetical pKa values. In the case of TCHC, the spectra were divided in two consecutive subdivisions according to their pH range having two pKa and TRAFA was run twice. The validity of the obtained pKa values was checked with well-known chemometrics algorithms such as DATAN, EQUSPEC, SPECFIT/32 and SQUAD. The effects of changing solvent composition on the protolytic constants were explained by linear solvation energy relationships (LSER) utilizing solvatochromic parameters. PMID- 21035377 TI - Regulating DnaA complex assembly: it is time to fill the gaps. AB - New rounds of bacterial chromosome replication are triggered during each cell division cycle by the initiator protein, DnaA. For precise timing, interactions of DnaA-ATP monomers with the replication origin, oriC, must be carefully regulated during formation of complexes that unwind origin DNA and load replicative helicase. Recent studies in Escherichia coli suggest that high and low affinity DnaA recognition sites are positioned within oriC to direct staged assembly of bacterial pre-replication complexes, with DnaA contacting low affinity sites as it oligomerizes to 'fill the gaps' between high affinity sites. The wide variability of oriC DnaA recognition site patterns seen in nature may reflect myriad gap-filling strategies needed to couple oriC function to the lifestyle of different bacterial types. PMID- 21035379 TI - Raman spectroscopic study of pascoite Ca3V10O(28).17H2O. AB - Raman spectroscopy has been used to study the molecular structure of the vanadate mineral pascoite. Pascoite, rauvite and huemulite are examples of simple salts involving the decavanadate anion (V10O28)6-. Decavanadate consists of four distinct VO6 units which are reflected in Raman bands occurring at higher wavenumbers. The Raman spectrum of pascoite is characterised by two intense bands at 991 and 965 cm(-1). Raman bands are observed at 991, 965, 958 and 905 cm(-1) and originate from four distinct VO6 sites in the mineral structure. In the infrared spectra of pascoite, two wavenumber regions are observed between: (1) 837 and 860, and (2) between 803 and 833 cm(-1). These bands are assigned to nu3 antisymmetric stretching modes of (V10O28)6- or (V5O14)3- units. The spectrum is highly complex in the lower wavenumber region, and therefore the assignment of bands is difficult. Bands observed in the 404 to 458 cm(-1) region are assigned to the nu2 bending modes of (V10O28)6- or (V5O14)3- units. Raman bands observed in the 530-620 cm(-1) region are assigned to the nu4 bending modes of (V10O28)6- or (V5O14)3- units. The Raman spectra of the vanadates in the low wavenumber region are complex with multiple overlapping bands which are probably due to VO subunits and MO bonds. PMID- 21035380 TI - Conjugate spacer effect on molecular structures and absorption spectra of triphenylamine dyes for sensitized solar cells: density functional theory calculations. AB - The molecular structures and absorption spectra of triphenylamine dyes containing variable thiophene units as the spacers (TPA1-TPA3) were investigated by density functional theory (DFT) and time-dependent DFT. The calculated results indicate that the strong conjugation is formed in the dyes and the length of conjugate bridge increases gradually with the increased thiophene spacers. The interfacial charge transfer between the TiO2 electrode and TPA1-TPA3 are electron injection processes from the excited dyes to the semiconductor conduction band. The simulated absorption bands are assigned to pi->pi* transitions, which exhibit appreciable red-shift with respect to the experimental bands due to the lack of direct solute-solvent interaction and the inherent approximations in TD-DFT. The effect of thiophene spacers on the molecular structures, absorption spectra and photovoltaic performance were comparatively discussed and points out that the choice of appropriate conjugate bridge is very important for the design of new dyes with improved performance. PMID- 21035381 TI - Quantitative determination of nicotinic acid in micro liter volume of urine sample by drop-to-drop solvent microextraction coupled to matrix assisted laser desorption/ionization mass spectrometry. AB - Drop-to-drop solvent microextraction (DDSME) coupled with matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS) for quantitative determination of nicotinic acid in one drop of urine sample has been proposed. All parameters, such as type of organic solvent, extraction time, exposure volume solvent, pH of the sample solution that affecting the separation and preconcentration of nicotinic acid were investigated. Under the optimal conditions, the detection limit of the method was 20 ng mL(-1) and the relative standard deviations (RSD) for determination of the nicotinic acid were in the range of 8.0-12.5%. The calculated calibration curves gave linearity in the range of 80-1000 ng mL(-1). The main advantages of the proposed method are simple, fast, and small amount of sample solution is used for separation and preconcentration of nicotinic acid. This method could be also useful for the analysis of other interested analytes in small volume of biological samples, like plasma, saliva and urine, where the availability of samples are limited. PMID- 21035382 TI - A sensitive resveratrol assay with a simple probe methylene blue by resonance light scattering technique. AB - A novel resonance light scattering (RLS) method was developed for the determination of resveratrol based on the interaction between resveratrol and methylene blue (MB). It was found that at pH 8.69, the weak RLS intensity of MB was remarkably enhanced by the addition of trace amount of resveratrol with the maximum peak located at 385.0 nm. Under the optimum conditions, a good linear relationship between the enhanced RLS intensities and the concentrations of resveratrol was obtained over the range of 2.0-14.0 MUg ml(-1) with the detection limit (3sigma) of 0.63 MUg ml(-1). The results of the analysis of resveratrol in synthetic samples and human urine are satisfactory, which showed it may provide a more sensitive, convenient, rapid and reproducible method for the detection of resveratrol, especially in biological and pharmaceutical field. In this work, the characteristics of RLS, absorption and fluorescence spectra of the resveratrol-MB system, the influencing factors and the optimum conditions of the reaction were investigated. PMID- 21035383 TI - eHealth in Belgium, a new "secure" federal network: role of patients, health professions and social security services. AB - eHealth platform is the official federal network in Belgium (created by law on 21 August 2008) devoted to a secure exchange of health data in many types of applications, such as health care purposes, simplification of administrative procedures and contribution to health policy. It implies a controlled access to decentralized databases and uses encrypted personal data. The national identification number has been chosen in order to authenticate the requester, the patient, and the receiver of information exchange. Authorizations have to be respected in order to obtain personal health data. Several questions are raised about its security: the lack of mandatory request for systematic journaling on accesses to the electronic patient record as well as the absence of explicit procedures for sanctions in case of unauthorized access, the new role of social security administration in managing security where a eHealth manager can be both judge and party (in the function of trusted third party for health data encryption and of a required lawyer for texts proposed by physicians to the Commission for the protection of private life). Another critic concerns the number of physicians in minority and the absence of patients' delegates in the eHealth Board. At a time when the patient is becoming a partner in the care team, should not he be the gate-keeper for the access to his own health record? How could networks help him to get the appropriate knowledge to contribute to care and to write his testament of life? Recent laws (on private life, patient rights and euthanasia) have contributed to a behavioural change in citizens and physician attitudes. Recommendations are made in order to improve the acceptability of eHealth platform. PMID- 21035384 TI - Epstein-Barr virus replication linked to B cell proliferation in inflamed areas of colonic mucosa of patients with inflammatory bowel disease. AB - BACKGROUND: Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract. Epstein-Barr virus (EBV) infection is associated with increased disease severity in therapeutically immunosuppressed IBD patients. The role of EBV infection in patients with IBD who are unresponsive to medical therapy is unclear. Anti-viral strategies may be a viable treatment option if severity of EBV infection, reflected in peripheral blood, contributes to IBD progression. OBJECTIVES: We investigated the role of EBV in IBD patients unresponsive to medical therapy by examining EBV reactivation and B-cell proliferation in colonic mucosa. STUDY DESIGN: EBV DNA copy numbers were measured by real-time PCR in peripheral blood mononuclear cells (PBMC) of 84 patients with IBD and 115 non-IBD controls in a retrospective cross-sectional study. EBV infected cells in colonic mucosa were identified by immunohistochemistry. RESULTS: EBV load in PBMC was higher in patients with IBD than in non-IBD controls, especially in patients not responding to medication. Inflamed colonic mucosa of these patients had high levels of expression of lytic and latent EBV genes that localized to proliferating B-lymphocytes, which was not seen in patients responding to therapy. CONCLUSIONS: EBV replication was associated with severe IBD and mucosal inflammation. Increased proliferation and EBV infection of B-lymphocytes in inflamed colonic mucosa highlight the potential role of EBV in mucosal inflammation. The immunomodulatory effects of EBV could delay the resolution of the IBD associated inflammation, thus contributing to disease progression. These results indicate that anti-viral therapeutic strategies for the resolution of IBD may be useful. PMID- 21035385 TI - Kinetics of cytokine and chemokine responses in patients with primary human herpesvirus 6 infection. AB - BACKGROUND: Cytokines and chemokines induced by human herpesvirus 6 (HHV-6) infection may play an important role in the observed HHV-6-associated clinical complications. However, basic data for cytokine and chemokine synthesis in primary HHV-6 infected patient without complication is lacking. OBJECTIVE: Aim of this study was to elucidate basic kinetic data for expressions of cytokines and chemokines in patients with primary HHV-6 infection without complication. STUDY DESIGN: Twenty-six patients suffering from fever were enrolled in this study. Fourteen biomarkers were measured in 74 serially collected sera samples from 26 patients. Additionally, serum samples obtained from 14 healthy children were used for control. RESULTS: Twenty of the 26 patients were diagnosed with primary HHV-6 infection based on viral isolation and serological analysis. The mean age (P=0.1289) and proportion of males to females (P=0.9999) between the patients with and without primary HHV-6 infection were not statistically different. At the acute phase of the disease, three cytokines (IFN-gamma; P=0.0046, IL-2; P=0.0366, and IL-4; P=0.0255) and one chemokine (MCP-1; P=0.0019) were significantly higher in patients with primary HHV-6 infection compared to those without infection. Interleukin-5 levels during the convalescent period were significantly higher in patients with HHV-6 infection (P=0.0205). By 1 month post-infection, cytokine and chemokine expression had returned to almost basal levels. CONCLUSION: As suggested by the previous in vitro studies, present in vivo analysis also suggests that HHV-6 has potency for induction of cytokines and chemokines. PMID- 21035386 TI - High-risk human papillomavirus DNA in paraaortic lymph nodes in advanced stages of cervical carcinoma. AB - BACKGROUND: Paraaortic lymph nodes represent the second level in the lymphatic spread of cervical cancer. Recent studies have confirmed the association of HPV DNA in pelvic lymph nodes in early-stage disease with metastatic involvement and a less favourable prognosis. OBJECTIVE: The aim of our study was to detect 13 high-risk genotypes of HPV in paraaortic nodes harvested from patients with FIGO IB2-IIIB tumours and correlate findings with histopathology. STUDY DESIGN: The study involved patients with advanced cervical cancer who had undergone low paraaortic lymphadenectomy. The cytobrush technique was used for perioperative sample collection from the tumour and fresh lymphatic tissue. Patients with non HPV related cancers were used as a control group. RESULTS: The study involved 24 cervical cancer patients. High-risk HPV DNA was found in the primary tumour of all cases and in PALN in 16 (67%) cases. The most frequent genotype was HPV 16, both in the tumour and in the paraaortic lymph nodes (83% and 54%, respectively). Metastatic involvement of paraaortic lymph nodes was identified in 8 cases (33%), which all were also HPV DNA positive. No HPV DNA was detected in PALN in any of 22 control group cases. CONCLUSIONS: Using the cytobrush technique, the presence of at least one HR HPV genotype in the primary tumour was identified in all the patients. The metastatically involved paraaortic lymph nodes always contained the DNA of at least one HPV genotype present in the primary tumour. Determination of clinical significance of HR HPV DNA presence in histologically negative lymph nodes requires further follow-up of the cohort. PMID- 21035387 TI - Epidemiology of human enterovirus 71 infections in France, 2000-2009. AB - BACKGROUND: Human enterovirus 71 (EV-71) emerged as a significant pathogen able to cause large outbreaks involving severe neurological cases and children fatalities in Asia. OBJECTIVES: To describe epidemiology of EV-71 infections in France. STUDY DESIGN: Fifty-nine patients admitted in 12 different hospitals from 1994 to 2009 were included. The entire VP1 coding gene of 58 EV-71 strains was sequenced and phylogenetic analyses were performed to assign strains to genogroups/subgenogroups and to compare French isolates to European and worldwide isolates. RESULTS: The median age of the patients was 1.04 years (9 days to 7 years). Among 46 documented EV-71 infections, 39 were self-limited. Seven children developed severe sepsis-like, respiratory or neurological complications. Among them, 2 children died from acute respiratory distress syndrome. All the EV 71 strains belonged to genogroup C: 31 isolates belonged to subgenogroup C1, 26 to subgenogroup C2 and 1 to subgenogroup C4. All the strains were genetically related to other European strains isolated at the same period of time. Although C1 isolates were predominant between 1994 and 2005, C2 strains have been predominant since 2007. No association was found between any genotype and the age or the clinical symptoms. CONCLUSIONS: The C4 subgenogroup, which was associated with large outbreaks in China, did not spread in France. It is important to monitor more carefully the EV-71 strains circulating in France to detect the introduction of new genetic variants that could be associated with major outbreaks. PMID- 21035388 TI - Diagnosis of acute hepatitis E by antibody and molecular testing: a study on 277 suspected cases. AB - BACKGROUND: Acute hepatitis due to hepatitis E virus (HEV) infection is both indigenous and imported to Europe. Few studies provide information about the role of HEV as an agent for acute hepatitis in Spain. OBJECTIVES: To investigate the frequency of the HEV infection among patients displaying acute hepatitis of unexplained origin in Spain, comparing the performance of two different diagnostic approaches. STUDY DESIGN: Specific IgM antibody and HEV RNA tests were used to study samples from 277 patients with acute hepatitis of unknown aetiology received during a six-year period. Samples were sent by 52 hospitals from almost all regions of Spain. RESULTS: Evidence of acute infection by HEV was obtained for 30 patients in total (10.8%), and 16 cases were unrelated to recent international travel. On samples from 158 patients tested for both anti-HEV IgM and HEV RNA at admission, the yield of IgM antibody testing (11.4%) was higher than the yield of HEV RNA testing (9.5%). CONCLUSIONS: HEV could be responsible in Spain of about 11% of cases of acute hepatitis of unknown origin overall, and of about 8% of cases unrelated to international travel or immigration. India and neighbour countries represent the highest risk for import of epidemic HEV strains into Spain. Both antibody assays and molecular tests are required to optimise the final yield of laboratory diagnosis. PMID- 21035389 TI - Complete sequence and phylogenetic characterisation of Crimean-Congo hemorrhagic fever virus from Afghanistan. PMID- 21035391 TI - Excitability testing: from nerve to muscle. PMID- 21035390 TI - Determining which mechanisms lead to activation in the motor cortex: a modeling study of transcranial magnetic stimulation using realistic stimulus waveforms and sulcal geometry. AB - OBJECTIVE: To determine which mechanisms lead to activation of neurons in the motor cortex during transcranial magnetic stimulation (TMS) with different current directions and pulse waveforms. METHODS: The total electric field induced in a simplified model of a cortical sulcus by a figure-eight coil was calculated using the finite element method (FEM). This electric field was then used as the input to determine the response of compartmental models of several types of neurons. RESULTS: The modeled neurons were stimulated at different sites: fiber bends for pyramidal tract neurons, axonal terminations for cortical interneurons and axon collaterals, and a combination of both for pyramidal association fibers. All neurons were more easily stimulated by a PA - directed electric field, except association fibers. Additionally, the second phase of a biphasic pulse was found to be more efficient than the first phase of either monophasic or biphasic pulses. CONCLUSIONS: The stimulation threshold for different types of neurons depends on the pulse waveform and relative current direction. The reported results might account for the range of responses obtained in TMS of the motor cortex when using different stimulation parameters. SIGNIFICANCE: Modeling studies combining electric field calculations and neuronal models may lead to a deeper understanding of the effect of the TMS-induced electric field on cortical tissue, and may be used to improve TMS coil and waveform design. PMID- 21035392 TI - Compare the effects of chondrogenesis by culture of human mesenchymal stem cells with various type of the chondroitin sulfate C. AB - Chondroitin sulfate C (CSC) is a kind of glycosaminoglycans (GAGs) with molecular weights of 10,000 to 50,000 Da and a high charge density. GAGs are major components in extracellular matrix (ECM), which play important role in the regulation of cell proliferation, migration, and differentiation. In this study, we studied the effects of chondroitin sulfate C (CSC) on the differentiation of human mesenchymal stem cells (MSCs) toward the chondrocyte lineage. The MSCs were either cultured on type II collagen (COL II) scaffolds with high molecular weight CSC addition in the medium (free CSC) or with free oligosaccharide CSC. Special attention was given to the effects of MSCs cultured on CSC cross-linked type II scaffolds (cross-linked CSC). According to the analysis of histology stain, gene expression, and ECM secretion, our results showed that MSCs cultured with free CSC, free oligosaccharides CSC, and on the cross-linked CSC scaffolds all would be induced into chondrocytes. Moreover, free oligosaccharide CSC present in the microenvironment could significantly up-regulate MSC chondrogenesis gene expression and stimulate cartilage ECM accumulation more than free CSC with high molecular weight after 3-week induction. Importantly, cross-linked CSC had the most excellent effects on the MSC chondrogenesis. Thus, we believed that cross linked CSC in the scaffold would play the similar roles with free oligosaccharide CSC in the medium. Cross-linked CSC would be a potential candidate for cartilage repair in the cell therapy and tissue engineering. PMID- 21035393 TI - Synthesis of chitosan-caffeic acid derivatives and evaluation of their antioxidant activities. AB - In this study, the antioxidant activities of different molecular weights (M(w)) and grafting ratios of chitosan-caffeic acid derivatives were investigated. The grafting process was achieved using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDAC) as covalent connector under different conditions such as molecular-weight of chitosan, molar ratio of chitosan and caffeic acid, reaction temperature, pH, and reaction time. The half-inhibition concentrations (IC50) of products were calculated by reduction of the 1,1 diphenyl picryl hydrazyl in the radical-scavenging assay and reduction of the Fe3+/ferricyanide complex to the ferrous form in reducing power assay. The EDAC showed maximum activity at 3-h, pH 5.0 and room temperature conditions, except high-molecular-weight chitosan in pH 2.0. The products were water-soluble in all pH and showed lower viscosity than native chitosan. The highest grafting ratio of caffeic acid was observed at 15% in low-molecular-weight chitosan. After 5% grafting of caffeic acid into chitosan, the grafting efficiency was increased by decreasing molecular-weight of chitosan at the same conditions. Caffeic acid has main role in the antioxidant activity of products. The maximum IC50 of radical scavenging activity (0.064 mg/ml) was observed at the highest caffeic acid containing derivative. Water-soluble chitosan and caffeic acid derivatives were obtained by this study without activity loss. PMID- 21035394 TI - Resolvase-like serine recombinase mediates integration/excision in the bacteriophage phiRSM. AB - phiRSM1, a filamentous phage infecting Ralstonia solanacearum, encodes an open reading frame (ORF14) that exhibits significant homology to members of the resolvase/invertase subfamily of site-specific serine recombinases. Similar prophages are found in the genomes of various strains of R. solanacearum, R. pickettii, and Burkholderia pseudomallei. We have characterized the integrative and excisive recombination reactions mediated by the phiRSM1 integrase using in vivo assays. An E. coli plasmid containing the RSM1 orf14 and attP sequences (pT orf14-attP) was shown to integrate into the attB sequence of R. solanacearum cells. Intermolecular recombination between pT-orf14-attP and pS-attB (a R. solanacearum plasmid containing attB) also occurred in R. solanacearum cells. The products of attP/attB recombination, i.e., attL and attR, were exactly identical to the sequences found in the prophage phiRSM in R. solanacearum strains. Intramolecular recombination between the attL and attR sequences (excisive recombination) on the pRecomb plasmid was also shown to occur in an orf14 dependent manner. This is the first evidence that a small serine recombinase from the resolvase/invertase group may function in integrative and excisive recombination for filamentous phages. PMID- 21035395 TI - Blood flow restriction by low compressive force prevents disuse muscular weakness. AB - Repetitive blood flow restriction prevents muscular atrophy and weakness induced by chronic unloading. However, it was unclear which external compressive force for blood flow restriction was optimal to prevent muscular dysfunction. The present study was intended to investigate the effects of repeated muscle blood flow restriction at low pressure on muscular weakness induced by immobilization without weight bearing. Using casts, the left ankles of 11 healthy males were immobilized for 2 weeks. Subjects were instructed to walk using crutches with no weight bearing during the period. Subjects were divided randomly into two groups: a restriction of blood flow (RBF) group (application of external compressive force of 50 mm Hg) and a control (CON) group (no intervention). We measured changes in the muscle strength of the knee extensor-flexor and ankle plantar flexor. The percent changes in knee extensor torque at 60 degrees /s under eccentric contraction in the RBF group were significantly smaller than in the CON group (-12.5+/-10.7% and -30.1+/-10.9%, p<0.05). The percent changes in knee flexor torque when performing an eccentric contraction at 60 degrees /s, an isometric contraction, or a concentric contraction at both 60 and 300 degrees /s in the RBF group were significantly smaller than those in the CON group (p<0.05). In conclusion, our results show that repetitive restriction of blood flow with 50 mm Hg cuff pressure to the lower extremity reduces muscular weakness induced by chronic unloading. PMID- 21035397 TI - Being underweight may reduce your ability to mobilise peripheral blood stem cells. AB - Being underweight is associated with a poorer outcome after haematopoietic stem cell transplantation (HSCT). We investigated whether nutritional status affects a patient's ability to mobilise stem cells. Weights, heights, peripheral blood CD34 counts and total collected stem cells were collected on 305 patients. Those patients who were underweight had a lower median peripheral blood CD34 count than those who were not underweight (36.0 vs. 53.0 * 10(6)/L (p = 0.0047)). However, the proportion of patients achieving a collection containing the minimum number of CD34 cells required to define a successful stem cell collection was similar in those who were underweight and those who were not. Therefore being underweight may reduce a patient's ability to mobilise peripheral blood stem cells and, if confirmed, improving nutritional status may reduce the number of patients who fail to mobilise. PMID- 21035396 TI - In vivo function of Langerhans cells and dermal dendritic cells. AB - In the past few years there has been an explosion in the characterization of skin resident dendritic cells (DCs). This is largely because of the development of several lines of mice with genetic alterations that allow for selective targeting of many of these subsets. There are now considerable data derived from in vivo experiments using these mice. This review focuses on the relative contribution of murine skin-resident DCs in the generation of immune responses to epicutaneous application of ovalbumin and during contact hypersensitivity. We describe a model in which the two best-characterized skin-resident DCs, langerhans cells (LCs) and Langerin(+) dermal DCs (dDCs) have distinct functions: Langerin(+) dDCs initiate and LCs suppress T cell responses. PMID- 21035398 TI - Remission of severe autoimmune bullous disorders induced by long-term extracorporeal photochemotherapy. AB - Pemphigus vulgaris (PV) and epidermolysis bullosa acquisita (EBA) sometimes resist treatments. In drug-resistant cases, adjuvant treatment with extracorporeal photochemotherapy (ECP) has been reported to induce remission. However, limited numbers of patients have been reported up to date. Eleven patients with drug-resistant autoimmune bullous diseases have been treated with ECP (8 patients with PV, 3 patients with EBA). The introduction of ECP to systemic therapies of the patients with PV resulted in complete response (CR) after a limited cycle (2-6 cycles) in all, except one patient. Prednisolone doses could be tapered in all patients. ECP resulted in CR in two patients while improvement was partial in one patient with EBA after 3-6 cycles. Our patients demonstrate the efficacy of long-term ECP to be tried in the treatment of aggressive autoimmune bullous disorders. The treatment has produced a remarkable corticosteroid-sparing effect while inducing clinical remission. PMID- 21035399 TI - Prediction of recovery of motor function after stroke. AB - BACKGROUND: Stroke is a leading cause of disability. The ability to live independently after stroke depends largely on the reduction of motor impairment and the recovery of motor function. Accurate prediction of motor recovery assists rehabilitation planning and supports realistic goal setting by clinicians and patients. Initial impairment is negatively related to degree of recovery, but inter-individual variability makes accurate prediction difficult. Neuroimaging and neurophysiological assessments can be used to measure the extent of stroke damage to the motor system and predict subsequent recovery of function, but these techniques are not yet used routinely. RECENT DEVELOPMENTS: The use of motor impairment scores and neuroimaging has been refined by two recent studies in which these investigations were used at multiple time points early after stroke. Voluntary finger extension and shoulder abduction within 5 days of stroke predicted subsequent recovery of upper-limb function. Diffusion-weighted imaging within 7 days detected the effects of stroke on caudal motor pathways and was predictive of lasting motor impairment. Thus, investigations done soon after stroke had good prognostic value. The potential prognostic value of cortical activation and neural plasticity has been explored for the first time by two recent studies. Functional MRI detected a pattern of cortical activation at the acute stage that was related to subsequent reduction in motor impairment. Transcranial magnetic stimulation enabled measurement of neural plasticity in the primary motor cortex, which was related to subsequent disability. These studies open interesting new lines of enquiry. WHERE NEXT?: The accuracy of prediction might be increased by taking into account the motor system's capacity for functional reorganisation in response to therapy, in addition to the extent of stroke-related damage. Improved prognostic accuracy could also be gained by combining simple tests of motor impairment with neuroimaging, genotyping, and neurophysiological assessment of neural plasticity. The development of algorithms to guide the sequential combinations of these assessments could also further increase accuracy, in addition to improving rehabilitation planning and outcomes. PMID- 21035400 TI - Energy metabolism in amyotrophic lateral sclerosis. AB - Amyotrophic lateral sclerosis (ALS) is characterised by the progressive degeneration of upper and lower motor neurons. Besides motor neuron degeneration, ALS is associated with several defects in energy metabolism, including weight loss, hypermetabolism, and hyperlipidaemia. Most of these abnormalities correlate with duration of survival, and available clinical evidence supports a negative contribution of defective energy metabolism to the overall pathogenic process. Findings from animal models of ALS support this view and provide insights into the underlying mechanisms. Altogether, these results have clinical consequences for the management of defective energy metabolism in patients with ALS and pave the way for future therapeutic interventions. PMID- 21035401 TI - Ranking of microRNA target prediction scores by Pareto front analysis. AB - Over the past ten years, a variety of microRNA target prediction methods has been developed, and many of the methods are constantly improved and adapted to recent insights into miRNA-mRNA interactions. In a typical scenario, different methods return different rankings of putative targets, even if the ranking is reduced to selected mRNAs that are related to a specific disease or cell type. For the experimental validation it is then difficult to decide in which order to process the predicted miRNA-mRNA bindings, since each validation is a laborious task and therefore only a limited number of mRNAs can be analysed. We propose a new ranking scheme that combines ranked predictions from several methods and - unlike standard thresholding methods - utilises the concept of Pareto fronts as defined in multi-objective optimisation. In the present study, we attempt a proof of concept by applying the new ranking scheme to hsa-miR-21, hsa-miR-125b, and hsa miR-373 and prediction scores supplied by PITA and RNAhybrid. The scores are interpreted as a two-objective optimisation problem, and the elements of the Pareto front are ranked by the STarMir score with a subsequent re-calculation of the Pareto front after removal of the top-ranked mRNA from the basic set of prediction scores. The method is evaluated on validated targets of the three miRNA, and the ranking is compared to scores from DIANA-microT and TargetScan. We observed that the new ranking method performs well and consistent, and the first validated targets are elements of Pareto fronts at a relatively early stage of the recurrent procedure, which encourages further research towards a higher dimensional analysis of Pareto fronts. PMID- 21035402 TI - Early vs. delayed diagnosis of severe combined immunodeficiency: a family perspective survey. AB - Infants affected with severe combined immunodeficiency (SCID) are susceptible to severe and recurrent infections and do not survive unless provided with immune reconstituting treatments. In the absence of population-based newborn screening, infants with SCID who do not have an affected older relative are ascertained only after they have developed infections. However, only limited data are available from the perspective of patients and families to indicate what proportion of SCID cases might benefit from earlier detection by pre-symptomatic screening, whether adequate treatment facilities are available, and how screening could improve SCID treatment outcomes. A survey of parents of children with SCID evaluated family history, pre- and post-diagnosis events, outcomes, and impact of SCID on families. Affected infants diagnosed with SCID as neonates had better survival, demonstrating the potential benefit of universal newborn screening. PMID- 21035403 TI - Evaluating the use of prolonged video-EEG monitoring to assess future seizure risk and fitness to drive. AB - OBJECTIVE: The use of prolonged video-electroencephalography monitoring (VEM), rather than routine electroencephalography (EEG), in predicting the risk of future seizures in patients with epilepsy is not well studied. A longer period of monitoring could be more likely to capture either ictal or interictal epileptiform activity. This information may better assist clinical decision making on driving fitness. The goal of this study was to evaluate the use of 6 hour prolonged VEM versus routine EEG in the assessment of future seizure risk and driving fitness for patients with epilepsy. METHODS: Data on consecutive patients referred for 6-hour prolonged VEM were retrospectively analyzed. Criteria were developed that combined EEG findings and clinical factors to determine each patient's fitness to drive. Seizure relapse outcomes were followed over 2 years. RESULTS: Of 34 patients, 27 were considered safe to drive following prolonged VEM. Five (19%) of these 27 patients had seizure relapses; all had an obvious precipitant(s) identified including sleep deprivation, excessive alcohol, and missed medication doses. Seven of the 34 patients were deemed unsafe to drive. All seven (100%) had seizure relapses, with unprovoked seizures in four patients. The relative risk of seizure in patients deemed unfit to drive was 5.4 (P=0.00015). If only the routine EEG component of the recordings were used with the criteria, the relative risk would have been 3.4 (P=0.037), with nearly double the number of active drivers having seizures. The majority of patients (76%) in this study had idiopathic generalized epilepsy, with a relative seizure risk of 4.0 (P=0.002) for patients deemed unfit to drive in this subgroup. The focal epilepsy group was small (eight patients) and did not quite achieve statistical significance. CONCLUSION: Six-hour VEM improves the evaluation of driving fitness by better predicting the risk of subsequent seizure relapse for idiopathic generalized epilepsy and possibly focal epilepsy. Prolonged monitoring is superior to routine EEG. Ongoing avoidance of seizure-provoking factors remains paramount to driving safety. PMID- 21035404 TI - Performance in recognition memory is correlated with entorhinal/perirhinal interictal metabolism in temporal lobe epilepsy. AB - In addition to the hippocampus, the entorhinal/perirhinal cortices are often involved in temporal lobe epilepsy (TLE). It has been proposed that these anterior parahippocampal structures play a key role in recognition memory. We studied the voxel-based PET correlation between number of correctly recognized targets in a new recognition memory paradigm and interictal cerebral metabolic rate for glucose, in 15 patients with TLE with hippocampal sclerosis. In comparison to healthy subjects, patients had decreased recognition of targets (P<0.001) and ipsilateral hypometabolism (relative to side of hippocampal sclerosis) of the hippocampus, entorhinal/perirhinal cortices, medial temporal pole, and middle temporal gyrus (P<0.05, corrected by false discovery rate method). Performance correlated with interictal metabolism of ipsilateral entorhinal/perirhinal cortices (P<0.005, Spearman's rank test), but this relationship was not significant in the hippocampus itself (P>0.18, Spearman's rank test). These findings highlight the preferential involvement of entorhinal/perirhinal cortices in recognition memory in patients with TLE, and suggest that recognition memory paradigms may be useful in assessing anterior parahippocampal functional status in TLE. PMID- 21035405 TI - Posttraumatic stress disorder caused by the misattribution of seizure-related experiential responses. AB - Patients with temporal lobe seizures sometimes experience what John Hughlings Jackson described as "dreamy states" during seizure onset. These phenomena may be characterized by a re-experiencing of past events, feelings of familiarity (deja vu), and hallucinations. In previous reports, patients have been aware of the illusory nature of their experiences. Here, however, the case of a patient with a documented 37-year history of temporal lobe epilepsy who is not aware is described. Fifteen years ago, the patient saw visions of traumatic autobiographical events that he had never previously recalled. He believed them to be veridical memories from his childhood, although evidence from his family suggests that they were not. The patient's psychological reaction to the "recovery" of these traumatic "memories" was severe enough to qualify as posttraumatic stress disorder (PTSD). To our knowledge, this is the first report of PTSD caused by the misattribution of mental states that accompany a seizure. PMID- 21035406 TI - CD4(+) T cells contribute to the remodeling of the microenvironment required for sustained tumor regression upon oncogene inactivation. AB - Oncogene addiction is thought to occur cell autonomously. Immune effectors are implicated in the initiation and restraint of tumorigenesis, but their role in oncogene inactivation-mediated tumor regression is unclear. Here, we show that an intact immune system, specifically CD4(+) T cells, is required for the induction of cellular senescence, shutdown of angiogenesis, and chemokine expression resulting in sustained tumor regression upon inactivation of the MYC or BCR-ABL oncogenes in mouse models of T cell acute lymphoblastic lymphoma and pro-B cell leukemia, respectively. Moreover, immune effectors knocked out for thrombospondins failed to induce sustained tumor regression. Hence, CD4(+) T cells are required for the remodeling of the tumor microenvironment through the expression of chemokines, such as thrombospondins, in order to elicit oncogene addiction. PMID- 21035408 TI - Assembly and function of DNA double-strand break repair foci in mammalian cells. AB - DNA double-strand breaks (DSBs) are among the most cytotoxic types of DNA damage, which if left unrepaired can lead to mutations or gross chromosomal aberrations, and promote the onset of diseases associated with genomic instability such as cancer. One of the most discernible hallmarks of the cellular response to DSBs is the accumulation and local concentration of a plethora of DNA damage signaling and repair proteins in the vicinity of the lesion, initiated by ATM-mediated phosphorylation of H2AX (gamma-H2AX) and culminating in the generation of distinct nuclear compartments, so-called Ionizing Radiation-Induced Foci (IRIF). The assembly of proteins at the DSB-flanking chromatin occurs in a highly ordered and strictly hierarchical fashion. To a large extent, this is achieved by regulation of protein-protein interactions triggered by a variety of post translational modifications including phosphorylation, ubiquitylation, SUMOylation, and acetylation. Over the last decade, insight into the identity of proteins residing in IRIF and the molecular underpinnings of their retention at these structures has been vastly expanded. Despite such advances, however, our understanding of the biological relevance of such DNA repair foci still remains limited. In this review, we focus on recent discoveries on the mechanisms that govern the formation of IRIF, and discuss the implications of such findings in light of our understanding of the physiological importance of these structures. PMID- 21035407 TI - Mre11-Rad50-Nbs1 conformations and the control of sensing, signaling, and effector responses at DNA double-strand breaks. AB - Repair and integrity of DNA ends at breaks, replication forks and telomeres are essential for life; yet, paradoxically, these responses are, in many cases, controlled by a single protein complex, Mre11-Rad50-Nbs1 (MRN). The MRN complex consists of dimers of each subunit and this heterohexamer controls key sensing, signaling, regulation, and effector responses to DNA double-strand breaks including ATM activation, homologous recombinational repair, microhomology mediated end joining and, in some organisms, non-homologous end joining. We propose that this is possible because each MRN subunit can exist in three or more distinct states; thus, the trimer of MRN dimers can exist in a stunning 6(3) or 216 states, a number that can be expanded further when post-translational modifications are taken into account. MRN can therefore be considered as a molecular computer that effectively assesses optimal responses and pathway choice based upon its states as set by cell status and the nature of the DNA damage. This extreme multi-state concept demands a paradigm shift from striving to understand DNA damage responses in separate terms of signaling, checkpoint, and effector proteins: we must now endeavor to characterize conformational and assembly states of MRN and other DNA repair machines that couple, coordinate, and control biological outcomes. Addressing the emerging challenge of gaining a detailed molecular understanding of MRN and other multi-state dynamic DNA repair machines promises to provide opportunities to develop master keys for controlling cell biology with probable impacts on therapeutic interventions. PMID- 21035409 TI - High-throughput characterization of lipopolysaccharide-binding proteins using mass spectrometry. AB - Lipopolysaccharide (LPS)-binding proteins interact with LPS in human serum and mediate various immune responses. We describe a high-throughput LPS-binding protein profiling platform for discovering unknown LPS-binding proteins and potential inflammatory mediators. As a pull-down method, the LPS molecules were immobilized onto epoxy beads and then directly incubated with human serum to screen LPS-binding proteins. Through the "untargeted" mass spectrometric approach, potential LPS-binding proteins which elicit various immune responses in human serum were identified by a highly sensitive LTQ Orbitrap Hybrid Fourier Transform Mass Spectrometer (LTQ Orbitrap FT MS). Therefore, this mass spectrometry (MS)-based profiling method is straightforward for screening unknown LPS-binding proteins and provides physiologically relevant binding partners in human serum. PMID- 21035411 TI - Indirect markers of non-alcoholic fatty liver disease: Another piece of the puzzle? PMID- 21035410 TI - [Determination of the diagnostic accuracy of 99mTc sestamibi scanning in patients with thyroid nodule and a definitive histopathological report]. AB - BACKGROUND: 99mTc sestamibi scanning and aspiration biopsy can predict the histopathological result of a thyroid nodule fairly accurately. OBJECTIVE: To determine the accuracy of 99mTc sestamibi scanning in detecting malignancy in patients with thyroid nodule confirmed by definitive histopathological report after thyroidectomy. MATERIAL AND METHODS: A total of 69 patients with a solitary thyroid nodule were studied. In all patients, fine needle aspiration, total thyroidectomy for suspected thyroid cancer, and histological analysis of the surgical specimen were performed. There were 54 patients with a positive 99mTc sestamibi scan; of these, malignancy was confirmed by histological analysis in 25 and excluded in 29. There were 15 patients with a negative 99mTc sestamibi scan; of these, three had a final diagnosis of cancer and 12 were confirmed as cancer free. RESULTS: The diagnostic accuracy of 99mTc sestamibi scanning in detecting malignancy in thyroid nodules was determined through a statistical analysis. 99mTc sestamibi scan for thyroid cancer had a sensitivity of 89.28% and a specificity of 29.25%. The positive predictive value was 46.29% and the negative predictive value was 80%. CONCLUSIONS: We believe that 99mTc sestamibi scan should be routinely used in all patients with a thyroid nodule and an indeterminate result on fine needle aspiration. This procedure is most useful in excluding malignancy in patients with a negative 99mTc sestamibi scan. PMID- 21035412 TI - Genomics in Aquaculture (GIA) 2009 symposium. PMID- 21035413 TI - From social to surgical: historical perspectives on perineal care during labour and birth. AB - A review of key historical texts that mentioned perineal care was undertaken from the time of Soranus (98-138 A.D.) to modern times as part of a PhD into perineal care. Historically, perineal protection and comfort were key priorities for midwives, most of whom traditionally practised under a social model of care. With the advent of the Man-Midwife in the seventeenth and eighteenth century, the perineum became pathologised and eventually a site for routine surgical intervention--most notably seen in the widespread use of episiotomy. There were several key factors that led to the development of a surgical rather than a social model in perineal care. These factors included a move from upright to supine birth positions, the preparation of the perineum as a surgical site through perineal shaving and elaborate aseptic procedures; and the distancing of the woman from her support people, and most notably from her own perineum. In the last 30 years, in much of the developed world, there has been a re-emergence of care aimed at preserving and protecting the perineum. A dichotomy now exists with a dominant surgical model competing with the re-emerging social model of perineal care. Historical perspectives on perineal care can help us gain useful insights into past practices that could be beneficial for childbearing women today. These perspectives also inform future practice and research into perineal care, whilst making us cautious about political influences that could lead to harmful trends in clinical practice. PMID- 21035414 TI - Total knee arthroplasty for osteoarthritis secondary to extra-articular malunions. AB - INTRODUCTION: Post-traumatic total knee arthroplasty for extra-articular malunion requires correction of the deformity, either through asymmetrical bone resection (possibly inducing ligaments imbalance) or osteotomy at the time of arthroplasty. We report the results of a continuous multicenter, retrospective series of 78 patients (18 implants with osteotomy) with a mean 4 years of follow-up. The hypothesis is that the selected procedure requires to be based on the deformity's location and severity. PATIENTS: With a mean age of 63 years (younger in the osteotomy group), 38 patients had femoral malunion, 36 had tibial malunion, and four had a combined malunion. There were 70 frontal deformities (48 varus and 22 valgus) and 10 rotational deformities, often diaphyseal, four of which more than 20 degrees . Twelve patients had a history of infection; eight had frontal laxity greater than 10 degrees , and 15 a limited range of motion in flexion. In 70 cases, semi- or nonconstrained implants were used, and in eight cases more constrained implants, including four hinge prostheses. RESULTS: We observed two deep infections, one case of avulsion of the extensor mechanism, and two cases of aseptic loosening with femoral malunion and varus deformity. Two osteotomies resulted in nonunion, one with internal fixation devices mobilization requiring revision using extension rods. The function and pain scores were significantly improved. The mobility improvements were moderate but did not compromise the surgical procedure main objective. The preoperative hip-knee angle was corrected with both techniques. Only the function score gain was greater for the isolated arthroplasty procedures. DISCUSSION AND CONCLUSION: The indications for arthroplasty alone were extended to 20 degrees varus and 15 degrees valgus, with no major residual laxity. Beyond 10 degrees , hinge prosthesis should be available. Associated osteotomy can correct rotational deformities that cannot be compensated with bone cuts. In deformities that are close to the joint, osteotomy facilitates implantation of moderately constrained prosthesis. This indication is based on CAT scan rotational deformities measurements because rotational deformities require an osteotomy, and/or the presence of extraligamentous deformity that cannot be reduced with collateral ligaments surgical release. LEVEL OF EVIDENCE: Level 4. Non-controlled retrospective study. PMID- 21035415 TI - Assessment of arthroscopic management of femoroacetabular impingement. A prospective multicenter study. AB - INTRODUCTION: Surgical treatment of femoroacetabular impingement can be performed under arthroscopic control, to limit associated morbidity. Encouraged by recent good reports, arthroscopy is replacing alternative techniques for this indication. HYPOTHESIS: Arthroscopy enables femoroacetabular impingement to be corrected with a low rate of associated morbidity. AIM OF STUDY: To assess the indications for and quality of the technique and its impact on preliminary results and complications. To investigate preoperative prognostic factors. PATIENT AND METHODS: One hundred and eleven hips in 110 patients (78 male, 32 female; mean age, 31 years) were operated on under arthroscopic control for femoroacetabular impingement, by six senior surgeons. Sixty-five patients showed no radiographic sign of osteoarthritis, and 36 showed grade-1 early osteoarthritis on the Tonnis scale. RESULTS: Mean WOMAC score rose from 60.3 preoperatively to 83 (p<0.001) at a mean 10 months' FU (range, 6-18 mo). Seventy seven percent of patients were satisfied or very satisfied with their result. Patients with early osteoarthritis had significantly lower WOMAC and satisfaction scores than those free of osteoarthritis. Operative crossover to open surgery occurred in only one case. Five patients (4%) had revision: total hip replacement or resurfacing. There were seven complications (6%): three cases of heterotopic ossification, one of crural palsy, one of pudendal palsy, one of labium majus necrosis, and one non-displacement stress fracture of the femoral head/neck junction (managed by non-weight-bearing). There was no palsy of the territory of the lateral cutaneous nerve of the thigh. DISCUSSION: Results confirmed the efficacy and low associated morbidity of arthroscopy in the management of femoroacetabular impingement. Short-term functional results matched those of the literature. Planning and assessment seem not yet to be fully standardized. Preoperative osteoarthritis on X-ray was associated with poorer functional results. This attitude does not seem to be indicated for hips showing evolved osteoarthritis (>grade 1). PMID- 21035416 TI - Clinical assessment of external rotation for the diagnosis of anterior shoulder hyperlaxity. AB - The aim of this study was to evaluate two methods of clinical assessment for external rotation of the shoulder to optimise the diagnosis of hyperlaxity in patients being selected for surgery for stabilisation of chronic anterior instability. External rotation was evaluated in 70 healthy student volunteers by two examiners (intertester study) using two methods of assessment at 15-day intervals (intratester study). The first method used was the protocol described for the Instability Severity Index Score (ISIS). In this case, the subject was evaluated in the sitting position, bilaterally with passive range of motion movements. The shoulder was considered hyperlax if ER1 was greater than 85 degrees . With the second, so-called "elbow on the table" (EOT) method, the subject was evaluated in the decubitus dorsal position, unilaterally with passive range of motion. The subject was considered to be hyperlax if ER1 was greater than 90 degrees . Kappa values for intra- and intertester agreement with the ISIS method were average, while they were satisfactory with the intraclass coefficient (ICC). Kappa values for inter- and intratester agreement with the EOT method were average and good, respectively. This tendency was confirmed by the ICC which went from good to excellent for the two examiners in both series of measurements using the EOT method, showing better reproducibility with this method. Our study confirms that the most reproducible method for assessing external rotation is obtained by unilateral assessment of the patient in the decubitus dorsal position, with passive range of motion. An ER1 of 90 degrees is the necessary threshold for hyperlaxity because of elbow retropulsion with this method, which provides immediate and visual evaluation and eliminates the necessity of goniometry. PMID- 21035417 TI - Descriptive epidemiology of mechanical hip pathology in adults under 50 years of age. Prospective series of 292 cases: Clinical and radiological aspects and physiopathological review. AB - Two hundred and ninety-two patients, aged between 16 and 50 years and presenting with mechanical hip pathology, were included in a prospective multicenter study. The descriptive study concerned the clinical examination and analysis of three X ray views (AP pelvic, Lequesne false profile and lateral axial view). The series comprised 62% males, mean age 35 years, with 53% right side and 22% bilateral involvement. Initial trauma was reported in 19% of cases, and direct familial history of hip pathology in 20%. Seventy percent of the patients played sports, 30% were high-level athletes, and 17% played combat sports. The physical impingement sign was present in 18% to 65% of cases depending on the variant studied. On imaging (n=241), 62% of hips showed osteoarthritis, with 25% at the evolved stage. In the series, as a whole, there was a 35% rate of dysplasia, 63% of impingement and 5% of normal X-ray results. The radiologic impingement aspects were 58% cam-type, 19% pincer-type and 23% mixed. Twenty-two percent of dysplasia cases showed signs of associated impingement. Pain experienced exclusively in flexion/internal rotation/adduction on examination showed little sensitivity (20%) but considerable specificity (86%) for the main diagnosis of impingement. The links between impingement and dysplasia are discussed, and an integrative schema of all risk factors is put forward. PMID- 21035418 TI - Arthroplasty following a septic arthritis history: a 53 cases series. AB - INTRODUCTION: The most feared complication of arthroplasty after septic arthritis (active or quiescent) on a degenerative joint is septic failure, but this risk is difficult to assess. The aim of the present study was to analyze the results of arthroplasties after septic arthritis of native knee and hip joints, in terms of functional results and infection control and to seek eventual risk factors of failure. PATIENTS AND METHODS: Fifty-three cases of septic arthritis treated by arthroplasty (31 knees and 22 hips) were retrospectively included. In case of evolutive septic arthritis (30 cases: 17 knees and 13 hips) failing to react to conservative treatment, arthroplasty was performed in a 2-stage procedure (a mean interval of 6 weeks between stages, and an associated antibiotic therapy for a mean 3 months were routinely respected). In case of previous arthritis considered to be cured (23 cases: 14 knees and nine hips), arthroplasty was performed with a 1-stage procedure, observing a mean interval of 5 years after the initial septic arthritis, and antibiotic therapy maintained until definitive microbiological results were obtained from joint cultures samples at surgery. No patients were lost to follow-up; minimum follow-up was 2 years, for a mean of 5 years. The final results were assessed in terms of functional outcome (on PMA functional score for hips and IKS score for knees) and successful eradication of infection. RESULTS: Two-stage arthroplasty was successful in 26 of the 30 cases of evolutive septic arthritis (87%), while the 1-stage procedure was successful in 22 of the 23 cases of quiescent septic arthritis (95%) (NS). Functional results were very good. No significant difference in functional outcome or successful eradication of infection was found between the 1- and 2-stage procedures. No significant difference in final outcome in terms of infection eradication was found between knees and hips. No clinical, microbiological or treatment-related criteria emerged as risk factors for septic failure. DISCUSSION: Arthroplasty after septic arthritis of the knee or hip using the present protocol (2-stage implantation in case of evolutive septic arthritis and a 1-stage procedure in case of quiescent septic arthritis) achieved very good functional results with a success rate of 87% for sepsis control in evolutive septic arthritis and of 95% in quiescent septic arthritis. LEVEL OF EVIDENCE: Level IV retrospective or historical series. PMID- 21035419 TI - Can we improve the indication for Bankart arthroscopic repair? A preliminary clinical study using the ISIS score. AB - The objectives of this study on arthroscopic treatment of chronic anterior shoulder instability were the collection of the current practices for this indication, their development as reported in the literature, and the analysis of preliminary results on a multicenter prospective series of Bankart arthroscopic procedures undertaken using a common technique on patients selected based on the Instability Severity Index Score (ISIS). This procedure predominates in the English-speaking world, whereas the Latarjet protocol is preferred in France. The choice between the two seems to be cultural since neither technique could be demonstrated to be superior in an analysis of 171 responses to an Internet questionnaire in this study. The literature reports disappointing results in the Bankart arthroscopic procedure and recent articles have researched the predictive factors for its failure. Eleven centers prospectively included 125 patients from 1 December 2007 to 30 November 2008. The inclusion criteria were recurrence of anterior instability and an ISIS less than or equal to four points out of 10. All the selected patients underwent capsuloligamentous reinsertion with a common minimal technique of at least three anchors and four sutures with the same postoperative protocol. At a mean follow-up of 18 months, four patients (3.2%) had experienced recurrence. For the 84 patients reexamined at 1 year, the Walch Duplay and Rowe scores were, respectively, 88.4 and 87.8 points out of 100. Subjectively, 88.1% of the patients declared they were satisfied and would undergo the intervention again. This study confirmed the use of the ISIS as a consultation tool. Only continuation of the study with a minimum follow-up of 3 years will allow us to validate the lower limit of the ISIS below which this technique could be proposed provided that it respects the technical prerequisite of at least four capsuloligamentous sutures. PMID- 21035420 TI - Can we improve radiological analysis of osseous lesions in chronic anterior shoulder instability? AB - Osseous lesions of the glenoid cavity and humeral head are predictive of recurrence after Bankart arthroscopic procedures. The objective of this study was to analyze, for each glenoid and humeral defect plain x-ray criteria of the Instability Severity Index Score (ISIS), two aspects: inter- and intraobserver reliability of their qualitative and quantitative assessment and correlations between positive criteria and their quantitative measurement. Thirty-one medical files were retained for evaluation of the glenoid and 26 for humeral notch assessment. The yes or no response for the ISIS criterion was completed by its quantitative measurement using the Griffiths and Sugaya CT methods for the glenoid and the P/R index calculation on plain x-rays with internal rotation for the Hill-Sachs lesion. Three observers provided two consecutive readings for each criterion. The analysis of the glenoid radiological criterion of the ISIS seems sufficiently reproducible for daily practice. When the evaluation is positive, bone loss is greater than 15%, without a maximum value established. In this study, the analysis of the ISIS humeral notch criterion was not reproducible. It can be improved using the P/R index and should be completed by CT imaging. PMID- 21035421 TI - A case of middle-ear angiosarcoma. AB - INTRODUCTION: Middle-ear angiosarcoma is a rare malignant tumor that requires early diagnosis to allow satisfactory removal. The objective of the present study was to describe and discuss the diagnosis and treatment of this rare malignant middle-ear tumor. CASE REPORT: A 12-year-old girl was admitted for a left retroauricular mass and a budding left external auditory canal tumor without associated peripheral facial nerve palsy. CT scan showed a mastoid-region tumor extending to the external auditory canal with mastoid and occipital bone-loss. Tumor removal used a retroauricular approach. Postoperative diagnosis was of angiosarcoma. At 12 months' regular follow-up, there were no signs of local recurrence. DISCUSSION AND CONCLUSION: Middle-ear angiosarcoma is a rare tumor, in which diagnosis is late because early symptoms are not specific. A multidisciplinary approach is essential for efficient management. PMID- 21035422 TI - Transmission deafness and tinnitus: what diagnosis? PMID- 21035423 TI - Lesion- and vessel-specific coronary artery calcium scores are superior to whole heart Agatston and volume scores in the diagnosis of obstructive coronary artery disease. AB - BACKGROUND: The whole-heart coronary artery calcium (CAC) score has poor predictive value for obstructive coronary artery disease (CAD). We hypothesized that vessel- and lesion-specific CAC scores are more accurate. OBJECTIVES: To evaluate the usefulness of vessel- and lesion-specific CAC in predicting obstructive CAD and to assess the incremental value added by the vessel- and lesion-specific CAC to the conventional whole-heart CAC approach. METHODS: Ninety one patients with CAC scores and invasive angiography (XRA) data were enrolled. Besides whole-heart CAC, Agatston score (AgSc) and volume score (VolSc) were measured individually for each lesion in the 4 major epicardial coronary arteries. Maximum and average lesion-specific scores in each vessel were also determined. For the primary analysis, obstructive CAD was defined as 50% diameter stenosis by XRA. RESULTS: Whole-heart AgSc and VolSc were not different between patients with and without obstructive CAD (P = .23 and P = .18), whereas vessel- and lesion-specific scores were (maximum lesion specific AgSc, P < .0001). Maximum lesion-specific AgSc had superior diagnostic performance compared with whole-heart AgSc (area under receiver operating characteristics, 0.71 vs 0.58). Overall sensitivity, specificity, and diagnostic accuracy were improved. When specificity was fixed at 80%, sensitivity of maximum lesion-specific AgSc was superior to whole-heart AgSc (56.6% vs 35.1%). Most importantly, with lesion specific AgSc, fewer patients were classified as "indeterminate" compared with whole-heart AgSc (17.9% vs 50%). CONCLUSIONS: Vessel- and lesion-specific CAC scores are superior to the whole-heart AgSc and VolSc in predicting obstructive CAD. This simple refinement in CAC scoring may significantly improve the clinical predictive role of CAC imaging. PMID- 21035424 TI - UMP kinase from Mycobacterium tuberculosis: Mode of action and allosteric interactions, and their likely role in pyrimidine metabolism regulation. AB - The pyrH-encoded uridine 5'-monophosphate kinase (UMPK) is involved in both de novo and salvage synthesis of DNA and RNA precursors. Here we describe Mycobacterium tuberculosis UMPK (MtUMPK) cloning and expression in Escherichia coli. N-terminal amino acid sequencing and electrospray ionization mass spectrometry analyses confirmed the identity of homogeneous MtUMPK. MtUMPK catalyzed the phosphorylation of UMP to UDP, using ATP-Mg2(+) as phosphate donor. Size exclusion chromatography showed that the protein is a homotetramer. Kinetic studies revealed that MtUMPK exhibits cooperative kinetics towards ATP and undergoes allosteric regulation. GTP and UTP are, respectively, positive and negative effectors, maintaining the balance of purine versus pyrimidine synthesis. Initial velocity studies and substrate(s) binding measured by isothermal titration calorimetry suggested that catalysis proceeds by a sequential ordered mechanism, in which ATP binds first followed by UMP binding, and release of products is random. As MtUMPK does not resemble its eukaryotic counterparts, specific inhibitors could be designed to be tested as antitubercular agents. PMID- 21035425 TI - Post-transcriptional regulation of the mitochondrial H(+)-ATP synthase: a key regulator of the metabolic phenotype in cancer. AB - A distinctive metabolic trait of tumors is their enforced aerobic glycolysis. This phenotype was first reported by Otto Warburg, who suggested that the increased glucose consumption of cancer cells under aerobic conditions might result from an impaired bioenergetic activity of their mitochondria. A central player in defining the bioenergetic activity of the cell is the mitochondrial H(+)-ATP synthase. The expression of its catalytic subunit beta-F1-ATPase is tightly regulated at post-transcriptional levels during mammalian development and in the cell cycle. Moreover, the down-regulation of beta-F1-ATPase is a hallmark of most human carcinomas. In this review we summarize our present understanding of the molecular mechanisms that participate in promoting the "abnormal" aerobic glycolysis of prevalent human carcinomas. The role of the ATPase Inhibitor Factor 1 (IF1) and of Ras-GAP SH3 binding protein 1 (G3BP1), controlling the activity of the H(+)-ATP synthase and the translation of beta-F1-ATPase mRNA respectively in cancer cells is emphasized. Furthermore, we underline the role of mitochondrial dysfunction as a pivotal player of tumorigenesis. PMID- 21035426 TI - Cyanobacterial NDH-1 complexes: novel insights and remaining puzzles. AB - Cyanobacterial NDH-1 complexes belong to a family of energy converting NAD(P)H:Quinone oxidoreductases that includes bacterial type-I NADH dehydrogenase and mitochondrial Complex I. Several distinct NDH-1 complexes may coexist in cyanobacterial cells and thus be responsible for a variety of functions including respiration, cyclic electron flow around PSI and CO(2) uptake. The present review is focused on specific features that allow to regard the cyanobacterial NDH-1 complexes, together with NDH complexes from chloroplasts, as a separate sub-class of the Complex I family of enzymes. Here, we summarize our current knowledge about structure of functionally different NDH-1 complexes in cyanobacteria and consider implications for a functional mechanism. This article is part of a Special Issue entitled: Regulation of Electron Transport in Chloroplasts. PMID- 21035427 TI - Transbilayer organization of membrane cholesterol at low concentrations: Implications in health and disease. AB - Cholesterol is an essential and representative lipid in higher eukaryotic cellular membranes and is often found distributed nonrandomly in domains in biological membranes. A large body of literature exists on the organization of cholesterol in plasma membranes or membranes with high cholesterol content. However, very little is known about organization of cholesterol in membranes containing low amounts of cholesterol such as the endoplasmic reticulum or inner mitochondrial membranes. In this review, we have traced the discovery and subsequent development of the concept of transbilayer cholesterol dimers (domains) in membranes at low concentrations. We have further discussed the role of membrane curvature and thickness on the transbilayer organization of cholesterol. Interestingly, this type of cholesterol organization could be relevant in cellular sorting and trafficking, and in pathological conditions. PMID- 21035428 TI - Electromediated formation of DNA complexes with cell membranes and its consequences for gene delivery. AB - Electroporation is a physical method to induce the uptake of therapeutic drugs and DNA, by eukaryotic cells and tissues. The phenomena behind electro-mediated membrane permeabilization to plasmid DNA have been shown to be significantly more complex than those for small molecules. Small molecules cross the permeabilized membrane by diffusion whereas plasmid DNA first interacts with the electropermeabilized part of the cell surface, forming localized aggregates. The dynamics of this process is still poorly understood because direct observations have been limited to scales of the order of seconds. Here, cells are electropermeabilized in the presence of plasmid DNA and monitored with a temporal resolution of 2 ms. This allows us to show that during the first pulse application, plasmid complexes, or aggregates, start to form at distinct sites on the cell membrane. FRAP measurements show that the positions of these sites are remarkably immobile during the application of further pluses. A theoretical model is proposed to explain the appearance of distinct interaction sites, the quantitative increase in DNA and also their immobility leading to a tentative explanation for the success of electro-mediated gene delivery. PMID- 21035430 TI - Relationship among fMRI, contrast sensitivity and visual acuity. AB - The purpose of this study was to ascertain whether visual acuity or contrast sensitivity function (CSF) is proportional to visual cortical function based on fMRI volume and level of activation or Z-score. Forced choice procedures were utilized to measure the monocular log minimal angle of resolution (logMAR) visual acuity and CSF. The CSF data were collapsed into a single index by the use of weighted mean contrast sensitivity (WMCS), being defined as the mean of the products of each spatial frequency multiplied by its corresponding contrast sensitivity. fMRI data had been obtained with a 1.5 T GE Signa scanner with visual stimuli including 1.0 and 2.0 c/deg vertical sinusoidal gratings. Subjects consisted of eight normal adults and five amblyopic patients, with the amblyopic subjects added to gauge whether the outcome was due to a restricted range of scores or the small number of study participants. In normal subjects, the fMRI volume and level of activation exhibited no statistically significant correlation with visual acuity at P<0.05. Statistically significant correlations were obtained between WMCS and fMRI volume (R=0.765, P=0.027) and fMRI level of activation (R=0.645, P=0.007), with right eye stimulation using the 1.0 c/deg grating. On the whole, statistically significant correlations between WMCS and fMRI parameters were maintained when subject age was held constant and when data from the five amblyopic subjects were included to expand the range of values and increase the number of data sets for analysis. fMRI volume and Z-score were more closely associated with the CSF, as defined by WMCS, than visual acuity. The results suggest that the CSF reflects the underlying visual cortical cells responsible for fMRI volume and the level of activation. PMID- 21035431 TI - Borobudur revisited: soy consumption may be associated with better recall in younger, but not in older, rural Indonesian elderly. AB - Previous reports have suggested that high frequent tofu consumption is associated with worse cognitive function in East Asian elderly. Some studies also found an increased risk of dementia with high tofu consumption in those older than 65years of age. Tofu and other soy products, such as tempeh, contain high levels of plant estrogens or isoflavones. This study revisited a rural Central Javanese population (56-97 years of age) who were covered by the Borobudur District Health Centers. Data on cognitive performance were available for n=142 participants. Results showed positive linear associations of weekly tofu (beta=.22, p<0.05) and tempeh (beta=.23, p<0.01) consumption with immediate recall, which were significant in those with an average age of 67 years. In those with an average age of 80 years, the earlier reported negative association of tofu with immediate recall was no longer significant. Lifestyle changes (reduction of tofu consumption after dissemination of results) or "healthy survivor effects" may have been responsible for this finding. These findings may be reminiscent of the "Window of Opportunity" theory, which suggests that estrogenic compounds can exert positive effects on verbal memory, but not in older men and women, when no or negative effects of these compounds on brain cells and cognition have been found. Long-term, placebo-controlled treatment studies should investigate whether tempeh, a fermented soybean product that also contains folate, can maintain cognitive function in middle-aged and elderly participants. PMID- 21035429 TI - Recombinant chimeric lectins consisting of mannose-binding lectin and L-ficolin are potent inhibitors of influenza A virus compared with mannose-binding lectin. AB - MBL structurally contains a type II-like collagenous domain and a carbohydrate recognition domain (CRD). We have recently generated three novel recombinant chimeric lectins (RCL), in which varying length of collagenous domain of mannose binding lectin (MBL) is replaced with that of L-ficolin (L-FCN). CRD of MBL is used for target recognition because it has a broad spectrum in pathogen recognition compared with L-FCN. Results of our study demonstrate that these RCLs are potent inhibitors of influenza A virus (IAV). RCLs, against IAV, show dose dependent activation of the lectin complement pathway, which is significantly higher than that of recombinant human MBL (rMBL). This activity is observed even without MBL-associated serine proteases (MASPs, provided by MBL deficient mouse sera), which have been thought to mediate complement activation. These observations suggest that RCLs are more efficient in associating with MASP-2, which predominantly mediates the activity. Yet, additional serum further increases the activity while RCL-mediated coagulation-like enzyme activities are diminished compared with rMBL, suggesting reduced association with MASP-1, which has been shown to mediate coagulation-like activity. These data suggest that RCLs may interfere less with host coagulation, which is advantageous to be a therapeutic drug. Importantly, these RCLs have surpassed rMBL for anti-viral activities, such as viral aggregation, reduction of viral hemagglutination (HA) and inhibition of virus-mediated HA and neuraminidase (NA) activities. These results are encouraging that novel RCLs could be used as anti-IAV agents with less side effect and that RCLs would be suitable candidates in developing a new anti-IAV therapy. PMID- 21035432 TI - Th17 cells in inflammation. AB - Naive T cells are multipotential precursors that differentiate into various effector subsets, such as T helper type 1 (Th1) and Th2 cells, which are characterized by their distinct functions. The IL-17-producing T helper (Th17) cell has been recently identified as a new subset of the T helper cell and a mediator of inflammation associated with various autoimmune diseases. Although several cytokines participate in Th17 cell development, IL-6 and TGF-beta are key factors for the generation of Th17 cells from naive T cells. On the other hand, IL-6 inhibits TGF-beta-induced regulatory T (Treg) cells, which suppress adaptive T cell responses and prevent autoimmunity. Recent studies suggest that it is an effective approach in the treatment of various autoimmune and inflammatory diseases to normalize the balance between Treg and Th17 cell development. Here, we review the discovery of the Th17 subset, its properties and relationship with several autoimmune diseases. PMID- 21035433 TI - Mepacrine treatment attenuates allergic airway remodeling segregated from airway inflammation in mice. AB - Asthma is a chronic airway disease characterized by increased airway hyperresponsiveness, airway inflammation, and airway remodeling including collagen deposition in subepithelial regions. We have shown earlier that mepacrine has anti-inflammatory activity and decreased the features of airway remodeling in a subacute model of asthma, when administered during the inflammatory phase. But it was not clear whether the reduction of airway remodeling by mepacrine was a direct effect or indirectly related to the reduction in the airway inflammation. In this study, we determined the effect of mepacrine on airway remodeling and airway hyperresponsiveness (AHR) in a chronic model of asthma which showed the features of airway inflammation in the initial stage (inflammation predominant stage) and airway remodeling with mild airway inflammation in a later stage (remodeling predominant stage). Mepacrine was administered only in the later stage that more accurately simulates human asthma, where airway remodeling already exists at the time of diagnosis. The remodeling predominant stage was associated with high levels of Th2 cytokines like IL-4 and IL-13, increase in the levels of profibrotic mediators such as arginase and TGF beta, and increased collagen deposition. These were efficiently attenuated by mepacrine treatment and led to a significant reduction in AHR. Thus, we conclude from this study that mepacrine has direct effects on established airway remodeling independent of its anti-inflammatory effects. PMID- 21035434 TI - Effects of 3-(2-Hydroxyphenyl)-1-(5-methyl-furan-2-y-l) propenone (HMP) upon signalling pathways of lipopolysaccharide-induced iNOS synthesis in RAW 264.7 cells. AB - We previously showed that 3-(2-hydroxyphenyl)-1-(5-methyl-furan-2-y-l)propenone (HMP), suppressed the synthesis of various proinflammatory mediators. In this study, HMP showed a dose-dependent inhibition of NO synthesis in the RAW 264.7 murine macrophage line. The inhibition of NO synthesis was related to inhibition of p38 phosphorylation and kinase activity that led to significant inhibition of phosphorylation of ATF-2. This effect in turn caused inhibition of AP-1-DNA binding which partially explains the inhibitory effect upon the synthesis of iNOS. HMP had no effect upon phosphorylation of JNK, ERK1/2 and STAT-1. Kinase activity of JNK and ERK1/2 was also not affected by HMP as determined by levels of phosphorylated c-jun and phosphorylated elk-1. Furthermore HMP failed to block phosphorylation of IkappaBalpha, and subsequent nuclear translocation and DNA binding activity of p65 NF-kappaB in IFN-gamma/LPS-induced RAW 264.7 cells. Molecular docking experiments confirmed that HMP fits well in the highly conserved hydrophobic pocket of p38 MAP kinase. We conclude that the synthetic HMP is a chalcone analogue that selectively inhibits the p38/ATF-2 and AP-1 signaling pathways in the NO synthesis by the macrophage RAW 264.7. PMID- 21035435 TI - Trace metal zinc stimulates secretion of antimicrobial peptide LL-37 from Caco-2 cells through ERK and p38 MAP kinase. AB - Infectious diseases, especially, diarrhoea, are responsible for high mortality rates in developing countries. Zinc supplementation shows beneficial effects against such diseases, but the mechanism of action is poorly understood. Here, we examined whether zinc supplementation can improve mucosal innate immunity through induction of antimicrobial peptide secretion from intestinal epithelial cells. Zinc was found to induce secretion of the antimicrobial peptide LL-37 from Caco-2 cell in a dose (0.63+/-0.09ng/mL and 0.54+/-0.06ng/mL at 20MUM and 50MUM respectively) and time dependent manner. LL-37 secretion increased immediately (1h) after exposure to 20MUM Zn (0.29+/-0.04ng/mL), which continued up to 48h of exposure (0.58+/-0.05ng/mL). Zinc induces the phosphorylation of ERK and p38 MAP kinase and regulates LL-37 secretion through these MAP kinases. Zinc supplementation may have beneficial effects on mucosal innate immunity via secretion of LL-37. PMID- 21035436 TI - beta-Lapachone-induced reactive oxygen species (ROS) generation mediates autophagic cell death in glioma U87 MG cells. AB - Autophagy is mainly responsible for the degradation of long-lived proteins and subcellular organelles. Autophagy is responsible for the non-apoptotic cell death, and plays a crucial role in regulating cellular functions. beta-Lapachone is a quinone-containing compound originally obtained from the lapacho tree in South America. Here, we show that beta-lapachone induces death in U87 MG cells, which is not inhibited by blockers of pan-caspase or necrosis. beta-Lapachone induced cell death gradually increased in a time-dependent manner in U87 MG cells, which were partly prevented by pretreatment of a specific inhibitor of NQO1 (dicoumarol). These results suggested that beta-lapachone-induced cell death was mediated by NQO1-independent as well as NQO1-dependent cell death pathways. During progression of beta-lapachone-induced cell death, translocation and processing of LC3 as well as an increase in acidic vesicular organelles, as assessed by acridine orange staining, were observed. Furthermore, beta-lapachone induced cell death was inhibited by either a knockdown of beclin-1/Atg-6 or Atg-7 gene expression or by autophagy inhibitors (3-methyl adenine or bafilomycin A1). Reactive oxygen species (ROS) were involved in beta-lapachone-induced autophagic cell death of U87 MG glioma cells, because beta-lapachone induced ROS production and antioxidant N-acetylcysteine (NAC) decreased autophagic cell death. Our results collectively demonstrate that ROS mediate beta-lapachone-induced autophagic cell death in U87 MG glioma cells. PMID- 21035437 TI - Post-translational regulation by gustavus contributes to selective Vasa protein accumulation in multipotent cells during embryogenesis. AB - Vasa is a broadly conserved DEAD-box RNA helicase associated with germ line development and is expressed in multipotent cells in many animals. During embryonic development of the sea urchin Strongylocentrotus purpuratus, Vasa protein is enriched in the small micromeres despite a uniform distribution of vasa transcript. Here we show that the Vasa coding region is sufficient for its selective enrichment and find that gustavus, the B30.2/SPRY and SOCS box domain gene, contributes to this phenomenon. In vitro binding analyses show that Gustavus binds the N-terminal and DEAD-box portions of Vasa protein independently. A knockdown of Gustavus protein reduces both Vasa protein abundance and its propensity for accumulation in the small micromeres, whereas overexpression of the Vasa-interacting domain of Gustavus (GusDeltaSOCS) results in Vasa protein accumulation throughout the embryo. We propose that Gustavus has a conserved, positive regulatory role in Vasa protein accumulation during embryonic development. PMID- 21035438 TI - Nkx6 genes pattern the frog neural plate and Nkx6.1 is necessary for motoneuron axon projection. AB - Neuronal subtypes originate from an undifferentiated neural epithelium that is progressively divided into progenitor domains by homeodomain transcription factors such as members of the Nkx family. Here we report the functional analysis of Nkx6.1 and Nkx6.2 in Xenopus. While Nkx6.2 is expressed early in a large region of the medial neural plate, Nkx6.1 is restricted to a region overlapping with the region of motor neuron formation. By mRNA injection we show that both can inhibit primary neurogenesis as well as expression of intermediate neural plate markers. However, they do not form auto-regulatory loops and fail to induce ectopic motor neurons as they do in the chick. Using morpholino-mediated knockdown in Xenopus laevis and Xenopus tropicalis we show that Nkx6.1 knockdown results in paralyzed tadpoles. Using DiI labeling and immunohistochemistry we show that the underlying mechanism is a failure of spinal motor neurons to extend axons to their targets. Analysis of neural pattern reveals that ventral Lhx3+ and Pax2+ interneurons are dependent on Nkx6.1 function, but overall neural patterning is not. This study illustrates that while important aspects of Nkx6 gene function are conserved in vertebrate neural patterning, others are not. PMID- 21035439 TI - Pitx2 is an upstream activator of extraocular myogenesis and survival. AB - The transcription factors required to initiate myogenesis in branchial arch- and somite-derived muscles are known, but the comparable upstream factors required during extraocular muscle development have not been identified. We show Pax7 is dispensable for extraocular muscle formation, whereas Pitx2 is cell-autonomously required to prevent apoptosis of the extraocular muscle primordia. The survival requirement for Pitx2 is stage-dependent and ends following stable activation of genes for the muscle regulatory factors (e.g. Myf5, MyoD), which is reduced in the absence of Pitx2. Further, PITX2 binds and activates transcription of the Myf5 and MyoD promoters, indicating these genes are direct targets. Collectively, these data demonstrate that PITX2 is required at several steps in the development of extraocular muscles, acting first as an anti-apoptotic factor in pre-myogenic mesoderm, and subsequently to activate the myogenic program in these cells. Thus, Pitx2 is the first demonstrated upstream activator of myogenesis in the extraocular muscles. PMID- 21035440 TI - Expression and interaction of muscle-related genes in the lamprey imply the evolutionary scenario for vertebrate skeletal muscle, in association with the acquisition of the neck and fins. AB - Gnathostomes (jawed vertebrates) possess skeletal muscles with unique functional and developmental features that are absent from cyclostomes-i.e., lamprey and hagfish. These gnathostome-specific traits include the epaxial and hypaxial division of myotomes, paired fin/limb muscles, shoulder girdle muscles, and the muscle associated with the tongue and the neck. Many of these muscles are derived from several rostral somites, specifically from their hypaxial myotomic domains. However, it has not been clarified how the complicated morphology of these muscles was acquired in the evolution of vertebrates. Here we describe the expression of lamprey homologs of transcription factor genes, including a myogenic regulatory factor of the Myod family (MRF), Pax3/7, Lbx, and Zic, which play important roles in the development of ep-/hypaxial somitic muscles in gnathostomes, and show that the ventral portion of lamprey somites is comparable to the ventral dermomyotome in gnathostomes. The supra- and infraoptic muscles, derived from the two anterior somites in the lamprey, are molecularly specified before their extensive invasion into the head region. Of these, the infraoptic myotomes are suggested to represent the cucullaris homologue in the lamprey based on their topographical position in the embryonic pattern. Slightly caudal myotomes in the lamprey give rise to the hypobranchial muscle, the developmental homologue of the gnathostome hypobranchial musculature. The dorsal moieties of the lamprey somites express a Zic gene, which in teleosts specifies the epaxial identities of the somites. These evidences suggest that, although the myotomes in the ancestral jawless vertebrates do not exhibit ep-/hypaxial distinction at the morphological level, their dorsoventral specification would have already been present at gene regulatory levels, prior to the cyclostome-gnathostome divergence, which may have functioned as the key innovation to establish the ep /hypaxial distinction in gnathostomes. PMID- 21035441 TI - Olprinone, a PDE3 inhibitor, modulates the inflammation associated with myocardial ischemia-reperfusion injury in rats. AB - Coronary ischemia and subsequent reperfusion result in deleterious effects, one of the principal ones being vascular and myocardial inflammation. Olprinone hydrochloride, a specific phosphodiesterase III inhibitor, has anti-inflammatory effects in addition to its inotropic and vasodilator effects. The purpose of this study was to examine the beneficial effects of olprinone on myocardial ischemia reperfusion injury. Myocardial ischemia-reperfusion injury was caused by clamping the LAD (left anterior descending) coronary artery for 25 min followed by a release of the clamp allowing reperfusion for 1 h. Olprinone i.p. (0.2 mg/kg, i.p.) was administrated 15 min after ischemia. The olprinone administration significantly reduced the: (1) histological evidence of myocardial injury, (2) pro-inflammatory cytokines: tumor necrosis factor-alpha (TNF-alpha) and Interleukin-1beta (IL-1beta), (3) adhesion molecules: Inter-Cellular Adhesion Molecule 1 (ICAM-1) and P-Selectin, (4) nitrotyrosine formation, (5) nuclear factor kappa-B (NF-kappaB) expression, (6) Poly (ADP-ribose) (PAR) formation, and (7) apoptosis (Bax, Bcl-2, Fas-L and terminal deoxynucleotidyl transferase mediated UTP end labeling (TUNEL). Based on these findings this study provides the evidence that treatment with olprinone ameliorated the inflammatory process associated with myocardial ischemia-reperfusion in rats and suggests that this drug may have potential in the treatment of various ischemia and reperfusion diseases. PMID- 21035442 TI - Elevated free fatty acids and impaired adiponectin bioactivity contribute to reduced SOD2 protein in monocytes of type 2 diabetes patients. AB - Type 2 diabetes (T2D) is characterized by increased oxidative stress contributing to the development of cardiovascular disease (CVD). Monocytes are critically important in the pathogenesis of CVD and antioxidant enzymes like superoxide dismutase (SOD2) protect these cells from excessive reactive oxygen species (ROS). Adiponectin is an adipocyte-derived protein with atheroprotective function and the effect of adiponectin on monocyte SOD2 was analyzed herein. Adiponectin upregulated SOD2 mRNA and dose- and time-dependently induced SOD2 protein in primary human monocytes. Elevated systemic free fatty acids (FFA) are commonly found in T2D patients and palmitic acid as well as oleic acid reduced monocyte SOD2 protein. Adiponectin mediated upregulation of SOD2, however, was not affected by FFA incubation. SOD2 protein was reduced in T2D monocytes compared to monocytes of age- and body mass index-matched healthy controls. Adiponectin still induced SOD2 in T2D monocytes but efficiency tended to be reduced. In summary this study indicates that elevated systemic free fatty acids and impaired adiponectin activity contribute to reduced SOD2 and most likely increased oxidative stress in T2D monocytes. PMID- 21035443 TI - Loss of Smad3 gives rise to poor soft callus formation and accelerates early fracture healing. AB - Smad3 is an intracellular signaling molecule in the transforming growth factor beta (TGF-beta) pathway that serves as a regulator of chondrogenesis and osteogenesis. To investigate the role of the TGF-beta/Smad3 signaling in the process of fracture healing, an open fracture was introduced in mouse tibiae, and the histology of the healing process was compared between wild-type (WT) and Smad3-null (KO) mice. In KO mice, the bone union formed more rapidly with less formation of cartilage in the callus and eventually the fracture was repaired more rapidly than in WT mice. Alkaline phosphatase staining showed that osteoblastic differentiation in the fracture callus was promoted in KO mice. Additionally, TRAP staining and the TUNEL assay revealed that the induction of osteoclasts and apoptotic cells was significantly promoted in the healing callus of KO mice. Sox9 expression clearly decreased at both mRNA and protein levels in the early stage of fracture in KO mice. In contrast, the expression of genes for osteogenesis and osteoclast formation increased from day 5 until day 14 post fracture in KO mice compared to WT mice. From these results, we concluded that the loss of TGF-beta/Smad3 signaling promoted callus formation by promoting osteogenesis and suppressing chondrogenesis, which resulted in faster fracture healing. PMID- 21035444 TI - Spatial correlation of mouse photoreceptor-RPE thickness between SD-OCT and histology. AB - Spectral Domain Optical Coherence Tomography (SD-OCT) applied to the mouse retina has been limited due to inherent movement artifacts and lack of resolution. Recently, SD-OCT scans from a commercially available imaging system have yielded retinal thickness values comparable to histology. However, these measurements are based on single point analysis of images. Here we report that using the Spectralis HRA + OCT Spectral Domain OCT and Fluorescein Angiography system (Heidelberg Engineering, Heidelberg, Germany), retinal thickness of linear expanses from SD-OCT data can be accurately assessed. This is possible by the development of a Spectralis-compatible ImageJ plug-in that imports 8-bit SLO and 32-bit OCT B-scan images, retaining scale and segmentation data and enabling analysis and 3D reconstruction. Moreover, mouse retinal layer thickness values obtained with this plug-in exhibit a high correlation to thickness measurements from histology of the same retinas. Thus, use of this ImageJ plug-in results in reliable quantification of long retinal expanses from in vivo SD-OCT images. PMID- 21035445 TI - Altered microRNA regulation in Huntington's disease models. AB - Huntington's disease (HD) is a genetic neurodegenerative disease caused by abnormal CAG expansion. MicroRNAs (miRNAs) are short RNA molecules regulating gene expression, and are implicated in a variety of diseases including HD. However, the profiles and regulation of miRNAs in HD are not fully understood. Here, we analyzed the miRNA expression and miRNA regulators in two transgenic models of HD, YAC128 and R6/2 mice, and in a 3-nitropropionic acid (3NP)-induced striatal degeneration rat model. After characterizing the phenotypes by behavioral tests and histological analyses, we profiled striatal miRNAs using a miRNA microarray and we measured the key molecules involved in miRNA biogenesis and function. YAC128 mice showed upregulation-dominant miRNA expressions at 5 months and downregulation-dominant expressions at 12 months. Concomitantly, the expressions of Drosha-DGCR8, Exportin-5, and Dcp1 were increased at 5months, and the expression of Dicer was decreased at 12 months. In 10-week-old R6/2 mice, downregulation was dominant in the miRNA expressions and the level of Drosha decreased concomitantly. Nine miRNAs (miR-22, miR-29c, miR-128, miR-132, miR-138, miR-218, miR-222, miR-344, and miR-674*) were commonly down-regulated in both the 12-month-old YAC128 and 10-week-old R6/2 mice. Meanwhile, 3NP rats showed dynamic changes in the miRNA profiles during disease development and a few miRNAs with altered expression. Our results show that transgenic HD mice have abnormal miRNA biogenesis. This information should aid in future studies on therapeutic application of miRNAs in HD. PMID- 21035446 TI - Protective immunity against Leishmania major induced by Leishmania tropica infection of BALB/c mice. AB - Leishmania (L.) tropica is a causative agent of human cutaneous and viscerotropic leishmaniasis. Immune response to L. tropica in humans and experimental animals are not well understood. We previously established that L. tropica infection induces partial protective immunity against subsequent challenge infection with Leishmania major in BALB/c mice. Aim of the present study was to study immunologic mechanisms of protective immunity induced by L. tropica infection, as a live parasite vaccine, in BALB/c mouse model. Mice were infected by L. tropica, and after establishment of the infection, they were challenged by L. major. Our findings shows that L. tropica infection resulted in protection against L. major challenge in BALB/c mice and this protective immunity is associated with: (1) a DTH response, (2) higher IFN-gamma and lower IL-10 response at one week post challenge, (3) lower percentage of CD4(+) lymphocyte at one month post-challenge, and (4) the source of IFN-gamma and IL-10 were mainly CD4(-) lymphocyte up to one month post-challenge suggesting that CD4(-) lymphocytes may be responsible for protection induced by L. tropica infection in the studied intervals. PMID- 21035447 TI - Decreased prereceptorial glucocorticoid activating capacity in starvation due to an oxidative shift of pyridine nucleotides in the endoplasmic reticulum. AB - Redox state of pyridine nucleotides of the endoplasmic reticulum (ER) lumen was determined in different nutritional conditions. NADPH-dependent cortisone reduction and NADP(+)-dependent cortisol oxidation were measured in rat liver microsomes, by utilizing the luminal 11beta-hydroxysteroid dehydrogenase type 1 activity. Cortisone reduction decreased, while cortisol oxidation increased during onward starvation, showing that the luminal NADPH/NADP(+) ratio was substantially decreased. Cortisone or metyrapone addition caused a smaller decrease in NADPH fluorescence in microsomes from starved rats. The results demonstrate that nutrient supply is mirrored by the redox state of ER luminal pyridine nucleotides. PMID- 21035448 TI - DHHC protein-dependent palmitoylation protects regulator of G-protein signaling 4 from proteasome degradation. AB - Regulator of G-protein signaling 4 (RGS4), an intracellular modulator of G protein coupled receptor (GPCR)-mediated signaling, is regulated by multiple processes including palmitoylation and proteasome degradation. We found that co expression of DHHC acyltransferases (DHHC3 or DHHC7), but not their acyltransferase-inactive mutants, increased expression levels of RGS4 but not its Cys2 to Ser mutant (RGS4C2S). DHHC3 interacts with and palmitoylates RGS4 but not RGS4C2S in vivo. Palmitoylation prolongs the half-life of RGS4 by over 8-fold and palmitoylated RGS4 blocked alpha(1A)-adrenergic receptor-stimulated intracellular Ca(2+) mobilization. Together, our findings revealed that DHHC proteins could regulate GPCR-mediated signaling by increasing RGS4 stability. PMID- 21035449 TI - An efflux pump is involved in secretion of newly synthesized siderophore by Pseudomonas aeruginosa. AB - Pseudomonas aeruginosa secretes the fluorescent siderophore, pyoverdine (PVD), to enable iron acquisition. Epifluorescence microscopy and cellular fractionation were used to investigate the role of an efflux pump, PvdRT-OpmQ, in PVD secretion. Bacteria lacking this efflux pump accumulated PVD, or a fluorescent precursor, in the periplasm, due to their inability to efficiently secrete into the media newly synthesized PVD. PvdRT-OpmQ is only the second system identified for secretion of newly synthesized siderophores by Gram negative bacteria. PMID- 21035450 TI - Androgens modulate song effort and aggression in Neotropical singing mice. AB - Androgens are an important class of steroid hormones involved in modulating the expression and evolution of male secondary sex characters. Vocalizations used in the context of aggression and mate attraction are among the most elaborate and diverse androgen-dependent animal displays as reflected in a rich tradition of studies on bird song and anuran calls. Male Alston's singing mice (Scotinomys teguina) commonly emit trilled songs that appear to function in male-male aggression. In this study, we experimentally manipulated androgens in singing mice to assess their role in modulating aggression and song effort. Testosterone- and DHT-treated animals retained aggressive and song attributes similarly. However, castrated mice administered empty implants showed more subordinate behavior and sang fewer songs that were shorter, lower in power, higher in frequency, and less stereotyped. The extensive effects of androgens on a suite of phenotypes highlight their role in linking gonadal status with decisions about investment in reproductive behaviors. PMID- 21035451 TI - Umbilical cord tissue-derived mesenchymal stem cells grow best under GMP compliant culture conditions and maintain their phenotypic and functional properties. AB - Mesenchymal stem cells (MSCs) are fibroblast-like multipotent stem cells that can differentiate into cell types of mesenchymal origin. Because of their immune properties and differentiation, potential MSCs are discussed for the use in tissue regeneration and tolerance induction in transplant medicine. This cell type can easily be obtained from the umbilical cord tissue (UCMSC) without medical intervention. Standard culture conditions include fetal bovine serum (FBS) which may not be approved for clinical settings. Here, we analyzed the phenotypic and functional properties of UCMSC under xeno-free (XF, containing GMP certified human serum) and serum-free (SF) culture conditions in comparison with standard UCMSC cultures. Phenotypically, UCMSC showed no differences in the expression of mesenchymal markers or differentiation capacity. Functionally, XF and SF-cultured UCMSC have comparable adipogenic, osteogenic, and endothelial differentiation potential. Interestingly, the UCMSC-mediated suppression of T cell proliferation in an allogeneic mixed lymphocyte reaction (MLR) is more effective in XF and SF media than in standard FBS-containing cultures. Regarding the mechanism of action of MLR suppression, transwell experiments revealed that in neither UCMSC culture a direct cell-cell contact is necessary for inhibiting T cell proliferation, and that the major effector molecule is prostaglandin E2 (PGE2). Taken together, GMP-compliant growth media qualify for long-term cultures of UCMSC which is important for a future clinical study design in regenerative and transplant medicine. PMID- 21035452 TI - A new isolate of Nosema sp. (Microsporidia, Nosematidae) from Phyllobrotica armata Baly (Coleoptera, Chrysomelidae) from China. AB - We studied the spore morphology and molecular systematics of a novel microsporidian isolate from Phyllobrotica armata Baly collected in China. The spores were long-oval and measured 4.7 * 2.6 MUm on fresh smears. Ultrastructure of the spores was characteristic for the genus Nosema: 13-14 polar filament coils, posterior vacuole, and a diplokaryon. The complete rRNA gene sequence of the isolate was 4308 bp long. The organization of the rRNA gene was 5'-LSU rRNA ITS-SSU rRNA-IGS-5S-3', which corresponds to that of the Nosema species. Phylogenetic analysis based on the rRNA gene sequence indicated that this isolate, designated as Nosema sp. PA, is closely related to Nosema bombycis and is correctly assigned to the "true"Nosema group. PMID- 21035453 TI - Endoplasmic reticulum chaperon tauroursodeoxycholic acid alleviates obesity induced myocardial contractile dysfunction. AB - ER stress is involved in the pathophysiology of obesity although little is known about the role of ER stress on obesity-associated cardiac dysfunction. This study was designed to examine the effect of ER chaperone tauroursodeoxycholic acid (TUDCA) on obesity-induced myocardial dysfunction. Adult lean and ob/ob obese mice were treated with TUDCA (50mg/kg/day, p.o.) or vehicle for 5 weeks. Oral glucose tolerance test (OGTT) was performed. Echocardiography, cardiomyocyte contractile and intracellular Ca(2+) properties were assessed. Sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) activity and protein expression of intracellular Ca(2+) regulatory proteins were measured using (45)Ca(2+) uptake and Western blot analysis, respectively. Insulin signaling, ER stress markers and HSP90 were evaluated. Our results revealed that chronic TUDCA treatment lowered systolic blood pressure and lessened glucose intolerance in obese mice. Obesity led to increased diastolic diameter, cardiac hypertrophy, compromised fractional shortening, cardiomyocyte contractile (peak shortening, maximal velocity of shortening/relengthening, and duration of contraction/relaxation) and intracellular Ca(2+) properties, all of which were significantly attenuated by TUDCA. TUDCA reconciled obesity-associated decrease in SERCA activity and expression, and increase in serine phosphorylation of IRS, total and phosphorylated cJun, ER stress markers Bip, peIF2alpha and pPERK. Obesity-induced changes in phospholamban and HSP90 were unaffected by TUDCA. In vitro finding revealed that TUDCA ablated palmitic acid-induced cardiomyocyte contractile dysfunction. In summary, these data depicted a pivotal role of ER stress in obesity-associated cardiac contractile dysfunction, suggesting the therapeutic potential of ER stress as a target in the management of cardiac dysfunction in obesity. PMID- 21035454 TI - betaIIPKC and epsilonPKC isozymes as potential pharmacological targets in cardiac hypertrophy and heart failure. AB - Cardiac hypertrophy is a complex adaptive response to mechanical and neurohumoral stimuli and under continual stressor, it contributes to maladaptive responses, heart failure and death. Protein kinase C (PKC) and several other kinases play a role in the maladaptative cardiac responses, including cardiomyocyte hypertrophy, myocardial fibrosis and inflammation. Identifying specific therapies that regulate these kinases is a major focus of current research. PKC, a family of serine/threonine kinases, has emerged as potential mediators of hypertrophic stimuli associated with neurohumoral hyperactivity in heart failure. In this review, we describe the role of PKC isozymes that is involved in cardiac hypertrophy and heart failure. This article is part of a special issue entitled "Key Signaling Molecules in Hypertrophy and Heart Failure". PMID- 21035456 TI - Inhibition of nonsense-mediated mRNA decay by antisense morpholino oligonucleotides restores functional expression of hERG nonsense and frameshift mutations in long-QT syndrome. AB - Mutations in the human ether-a-go-go-related gene (hERG) cause long-QT syndrome type 2 (LQT2). We previously described a homozygous LQT2 nonsense mutation Q1070X in which the mutant mRNA is degraded by nonsense-mediated mRNA decay (NMD) leading to a severe clinical phenotype. The degradation of the Q1070X transcript precludes the expression of truncated but functional mutant channels. In the present study, we tested the hypothesis that inhibition of NMD can restore functional expression of LQT2 mutations that are targeted by NMD. We showed that inhibition of NMD by RNA interference-mediated knockdown of UPF1 increased Q1070X mutant channel protein expression and hERG current amplitude. More importantly, we found that specific inhibition of downstream intron splicing by antisense morpholino oligonucleotides prevented NMD of the Q1070X mutant mRNA and restored the expression of functional Q1070X mutant channels. The restoration of functional expression by antisense morpholino oligonucleotides was also observed in LQT2 frameshift mutations. Our findings suggest that inhibition of NMD by antisense morpholino oligonucleotides may be a potential therapeutic approach for some LQT2 patients carrying nonsense and frameshift mutations. PMID- 21035455 TI - Calcium binding kinetics of troponin C strongly modulate cooperative activation and tension kinetics in cardiac muscle. AB - Tension development and relaxation in cardiac muscle are regulated at the thin filament via Ca(2+) binding to cardiac troponin C (cTnC) and strong cross-bridge binding. However, the influence of cTnC Ca(2+)-binding properties on these processes in the organized structure of cardiac sarcomeres is not well-understood and likely differs from skeletal muscle. To study this we generated single amino acid variants of cTnC with altered Ca(2+) dissociation rates (k(off)), as measured in whole troponin (cTn) complex by stopped-flow spectroscopy (I61Q cTn>WT cTn>L48Q cTn), and exchanged them into cardiac myofibrils and demembranated trabeculae. In myofibrils at saturating Ca(2+), L48Q cTnC did not affect maximum tension (T(max)), thin filament activation (k(ACT)) and tension development (k(TR)) rates, or the rates of relaxation, but increased duration of slow phase relaxation. In contrast, I61Q cTnC reduced T(max), k(ACT) and k(TR) by 40-65% with little change in relaxation. Interestingly, k(ACT) was less than k(TR) with I61Q cTnC, and this difference increased with addition of inorganic phosphate, suggesting that reduced cTnC Ca(2+)-affinity can limit thin filament activation kinetics. Trabeculae exchanged with I61Q cTn had reduced T(max), Ca(2+) sensitivity of tension (pCa(50)), and slope (n(H)) of tension-pCa, while L48Q cTn increased pCa(50) and reduced n(H). Increased cross-bridge cycling with 2-deoxy-ATP increased pCa(50) with WT or L48Q cTn, but not I61Q cTn. We discuss the implications of these results for understanding the role of cTn Ca(2+) binding properties on the magnitude and rate of tension development and relaxation in cardiac muscle. PMID- 21035457 TI - Fluorescence-based assay to measure the real-time kinetics of nucleotide incorporation during transcription elongation. AB - Understanding the mechanism and fidelity of transcription by the RNA polymerase (RNAP) requires measurement of the dissociation constant (K(d)) of correct and incorrect NTPs and their incorporation rate constants (k(pol)). Currently, such parameters are obtained from radiometric-based assays that are both tedious and discontinuous. Here, we report a fluorescence-based assay for measuring the real time kinetics of single-nucleotide incorporation during transcription elongation. The fluorescent adenine analogue 2-aminopurine was incorporated at various single positions in the template or the nontemplate strand of the promoter-free elongation substrate. On addition of the correct NTP to the T7 RNAP-DNA, 2 aminopurine fluorescence increased rapidly and exponentially with a rate constant similar to the RNA extension rate obtained from the radiometric assay. The fluorescence stopped-flow assay, therefore, provides a high-throughput way to measure the kinetic parameters of RNA synthesis. Using this assay, we report the k(pol) and K(d) of all four correct NTP additions by T7 RNAP, which showed a range of values of 145-190 s(-1) and 28-124 MUM, respectively. The fluorescent elongation substrates were used to determine the misincorporation kinetics as well, which showed that T7 RNAP discriminates against incorrect NTP both at the nucleotide binding and incorporation steps. The fluorescence-based assay should be generally applicable to all DNA-dependent RNAPs, as they use similar elongation substrates. It can be used to elucidate the mechanism, fidelity, and sequence dependency of transcription and is a rapid means to screen for inhibitors of RNAPs for therapeutic purposes. PMID- 21035458 TI - Effects of salts on internal DNA pressure and mechanical properties of phage capsids. AB - Based on atomic force microscopy nanoindentation measurements of phage lambda, we previously proposed a minimal model describing the effect of water hydrating DNA that strengthens viral capsids against external deformation at wild-type DNA packing density. Here, we report proof of this model by testing the prediction that DNA hydration forces can be dramatically decreased by addition of multivalent ions (Mg(2+) and Sp(4+)). These results are explained using a DNA hydration model without adjustable parameters. The model also predicts the stiffness of other DNA-filled capsids, which we confirm using bacteriophage phi29 and herpes simplex virus type 1 particles. PMID- 21035459 TI - A new clustering of antibody CDR loop conformations. AB - Previous analyses of the complementarity-determining regions (CDRs) of antibodies have focused on a small number of "canonical" conformations for each loop. This is primarily the result of the work of Chothia and coworkers, most recently in 1997. Because of the widespread utility of antibodies, we have revisited the clustering of conformations of the six CDR loops with the much larger amount of structural information currently available. In this work, we were careful to use a high-quality data set by eliminating low-resolution structures and CDRs with high B-factors or high conformational energies. We used a distance function based on directional statistics and an effective clustering algorithm with affinity propagation. With this data set of over 300 nonredundant antibody structures, we were able to cover 28 CDR-length combinations (e.g., L1 length 11, or "L1-11" in our CDR-length nomenclature) for L1, L2, L3, H1, and H2. The Chothia analysis covered only 20 CDR-lengths. Only four of these had more than one conformational cluster, of which two could easily be distinguished by gene source (mouse/human; kappa/lambda) and one could easily be distinguished purely by the presence and the positions of Pro residues (L3-9). Thus, using the Chothia analysis does not require the complicated set of "structure-determining residues" that is often assumed. Of our 28 CDR-lengths, 15 have multiple conformational clusters, including 10 for which the Chothia analysis had only one canonical class. We have a total of 72 clusters for non-H3 CDRs; approximately 85% of the non-H3 sequences can be assigned to a conformational cluster based on gene source and/or sequence. We found that earlier predictions of "bulged" versus "nonbulged" conformations based on the presence or the absence of anchor residues Arg/Lys94 and Asp101 of H3 have not held up, since all four combinations lead to a majority of conformations that are bulged. Thus, the earlier analyses have been significantly enhanced by the increased data. We believe that the new classification will lead to improved methods for antibody structure prediction and design. PMID- 21035460 TI - High-resolution crystal structures of trimeric and rod phycocyanin. AB - The phycobilisome light-harvesting antenna in cyanobacteria and red algae is assembled from two substructures: a central core composed of allophycocyanin surrounded by rods that always contain phycocyanin (PC). Unpigmented proteins called linkers are also found within the rods and core. We present here two new structures of PC from the thermophilic cyanobacterium Thermosynechococcus vulcanus. We have determined the structure of trimeric PC to 1.35 A, the highest resolution reported to date for this protein. We also present a structure of PC isolated in its intact and functional rod form at 1.5 A. Analysis of rod crystals showed that in addition to the alpha and beta PC subunit, there were three linker proteins: the capping rod linker (L(R)(8.7)), the rod linker (L(R)), and only one of three rod-core linkers (L(RC), CpcG4) with a stoichiometry of 12:12:1:1:1. This ratio indicates that the crystals contained rods composed of two hexamers. The crystallographic parameters of the rod crystals are nearly identical with that of the trimeric form, indicating that the linkers do not affect crystal packing and are completely embedded within the rod cavities. Absorption and fluorescence emission spectra were red-shifted, as expected for assembled rods, and this could be shown for the rod in solution as well as in crystal using confocal fluorescence microscopy. The crystal packing imparts superimposition of the three rod linkers, canceling out their electron density. However, analysis of B-factors and the conformations of residues facing the rod channel indicate the presence of linkers. Based on the experimental evidence presented here and a homology-based model of the L(R) protein, we suggest that the linkers do not in fact link between rod hexamers but stabilize the hexameric assembly and modify rod energy absorption and transfer capabilities. PMID- 21035461 TI - Multichromatic control of gene expression in Escherichia coli. AB - Light is a powerful tool for manipulating living cells because it can be applied with high resolution across space and over time. We previously constructed a red light-sensitive Escherichia coli transcription system based on a chimera between the red/far-red switchable cyanobacterial phytochrome Cph1 and the E. coli EnvZ/OmpR two-component signaling pathway. Here, we report the development of a green light-inducible transcription system in E. coli based on a recently discovered green/red photoswitchable two-component system from cyanobacteria. We demonstrate that the transcriptional output is proportional to the intensity of green light applied and that the green sensor is orthogonal to the red sensor at intensities of 532-nm light less than 0.01 W/m(2). Expression of both sensors in a single cell allows two-color optical control of transcription both in batch culture and in patterns across a lawn of engineered cells. Because each sensor functions as a photoreversible switch, this system should allow the spatial and temporal control of the expression of multiple genes through different combinations of light wavelengths. This feature aids precision single-cell and population-level studies in systems and synthetic biology. PMID- 21035462 TI - Crystal structure of the phage T4 recombinase UvsX and its functional interaction with the T4 SF2 helicase UvsW. AB - Bacteriophage T4 provides an important model system for studying the mechanism of homologous recombination. We have determined the crystal structure of the T4 UvsX recombinase, and the overall architecture and fold closely resemble those of RecA, including a highly conserved ATP binding site. Based on this new structure, we reanalyzed electron microscopy reconstructions of UvsX-DNA filaments and docked the UvsX crystal structure into two different filament forms: a compressed filament generated in the presence of ADP and an elongated filament generated in the presence of ATP and aluminum fluoride. In these reconstructions, the ATP binding site sits at the protomer interface, as in the RecA filament crystal structure. However, the environment of the ATP binding site is altered in the two filament reconstructions, suggesting that nucleotide cannot be as easily accommodated at the protomer interface of the compressed filament. Finally, we show that the phage helicase UvsW completes the UvsX-promoted strand-exchange reaction, allowing the generation of a simple nicked circular product rather than complex networks of partially exchanged substrates. PMID- 21035463 TI - Fab'-induced folding of antigenic N-terminal peptides from intrinsically disordered HIV-1 Tat revealed by X-ray crystallography. AB - Tat, the transcriptional activator protein of human immunodeficiency virus type 1 (HIV-1), is critical for viral replication and is a potential HIV-1 vaccine candidate. This intrinsically disordered protein is present in the extracellular medium and is involved in the pathogenicity of HIV through its interaction with different cellular and viral biological partners. A monoclonal antibody termed 11H6H1, which is specific for the N-terminal region of Tat, was selected for a functional and structural study of the HIV-1 Tat protein. The equilibrium dissociation constants (K(d)) of Tat and Tat fragments complexed with 11H6H1 were estimated by competitive ELISA. Tat contains a single tryptophan residue, Trp11, located in the N-terminal region. We show that the substitution of Trp11 by a phenylalanine completely abolishes the binding of 11H6H1, whereas the transactivating activity of Tat is preserved. The epitope recognized by 11H6H1 was restricted to the 9-mer peptide P(6)KLEPWKHP(14) centered on Trp11. The crystal structures of this 9-mer peptide and of an overlapping 15-mer peptide were determined in complex with Fab' 11H6H1 at 2.4 A and 2.1 A resolution, respectively. Tat is intrinsically disordered and can undergo induced folding upon association with a biological partner. Our crystallographic study reveals that the two Tat peptides, which are lodged in the U-shaped groove of the Fab' antigen-binding site, adopt a standard type I beta-turn conformation. The central Trp11 that is critical for Fab' recognition is further stabilized by pi-stacking interactions. The structural and biological consequences of this induced folding in HIV pathogenesis are discussed. PMID- 21035464 TI - Contract theory for the evolution of cooperation: The right incentives attract the right partners. AB - Partner choice is a critical stage of many biological interactions, from mating to cooperation. When the quality of the potential partners is unknown, one way to choose is to rely on signaling: costly signals can reveal the quality of the sender and allow the receiver to choose. In some cases, however, signaling (or an active choice based on signals) is not possible, for example in the initiation of the symbiosis between the squid Euprymna scolopes and the bioluminescent bacterium Vibrio fischeri. How is partner choice possible in this and other similar cases? I show that in a game with asymmetric information without signaling, imposing a deliberate cost for establishing the interaction allows the non-informed individual to attract the right partner if the cost induces only high quality individuals to accept the interaction. Furthermore, imposing different costs and rewards may induce the informed individuals to screen themselves according to their types, and therefore allow the non-informed individual to establish an association with the correct partners in the absence of signaling. PMID- 21035465 TI - Prediction of protein interaction hot spots using rough set-based multiple criteria linear programming. AB - Protein-protein interactions are fundamentally important in many biological processes and it is in pressing need to understand the principles of protein protein interactions. Mutagenesis studies have found that only a small fraction of surface residues, known as hot spots, are responsible for the physical binding in protein complexes. However, revealing hot spots by mutagenesis experiments are usually time consuming and expensive. In order to complement the experimental efforts, we propose a new computational approach in this paper to predict hot spots. Our method, Rough Set-based Multiple Criteria Linear Programming (RS MCLP), integrates rough sets theory and multiple criteria linear programming to choose dominant features and computationally predict hot spots. Our approach is benchmarked by a dataset of 904 alanine-mutated residues and the results show that our RS-MCLP method performs better than other methods, e.g., MCLP, Decision Tree, Bayes Net, and the existing HotSprint database. In addition, we reveal several biological insights based on our analysis. We find that four features (the change of accessible surface area, percentage of the change of accessible surface area, size of a residue, and atomic contacts) are critical in predicting hot spots. Furthermore, we find that three residues (Tyr, Trp, and Phe) are abundant in hot spots through analyzing the distribution of amino acids. PMID- 21035466 TI - Inducible COX-2 dominates over COX-1 in prostacyclin biosynthesis: mechanisms of COX-2 inhibitor risk to heart disease. AB - AIM: Our aim is to understand the molecular mechanisms of the selective nonsteroidal anti-inflammatory drugs (NSAID), cyclooxygenase-2 (COX-2) inhibitors', higher "priority" to reduce synthesis of the vascular protector, prostacyclin (PGI2), compared to that of nonselective NSAIDs. MAIN METHODS: COX-1 or COX-2 was co-expressed with PGI2 synthase (PGIS) in COS-7 cells. The Km and initial velocity (1/2t Vmax) of the coupling reaction between COX-1 and COX-2 to PGIS were established. The experiment was further confirmed by a kinetics study using hybrid enzymes linking COX-1 or COX-2 to PGIS. Finally, COX-1 or COX-2 and PGIS were respectively fused to red (RFP) and cyanic (CFP) fluorescence proteins, and co-expressed in cells. The distances between COXs and PGIS were compared by FRET. KEY FINDINGS: The Km for converting arachidonic acid (AA) to PGI2 by COX-2 coupled to PGIS is ~2.0MUM; however, it was 3-fold more (~6.0MUM) for COX-1 coupled to PGIS. The Km and 1/2t Vmax for COX-2 linked to PGIS were ~2.0MUM and 20s, respectively, which were 2-5 folds faster than that of COX-1 linked to PGIS. The FRET study found that the distance between COX-2-RFP and PGIS-CFP is shorter than that between COX-1-RFP and PGIS-CFP. SIGNIFICANCE: The study provided strong evidence suggesting that the low Km, faster 1/2t Vmax, and closer distance are the basis for COX-2 dominance over COX-1 (coupled to PGIS) in PGI2 synthesis, and further demonstrated the mechanisms of selective COX-2 inhibitors with higher potential to reduce synthesis of the vascular protector, PGI2. PMID- 21035467 TI - Phosphorylated hMSH6: DNA mismatch versus DNA damage recognition. AB - DNA mismatch repair (MMR) maintains genomic integrity by correction of mispaired bases and insertion-deletion loops. The MMR pathway can also trigger a DNA damage response upon binding of MutSalpha to specific DNA lesions such as O(6)methylguanine (O(6)meG). Limited information is available regarding cellular regulation of these two different pathways. Within this report, we demonstrate that phosphorylated hMSH6 increases in concentration in the presence of a G:T mismatch, as compared to an O(6)meG:T lesion. TPA, a kinase activator, enhances the phosphorylation of hMSH6 and binding of hMutSalpha to a G:T mismatch, though not to O(6)meG:T. UCN-01, a kinase inhibitor, decreases both phosphorylation of hMSH6 and binding of hMutSalpha to G:T and O(6)meG:T. HeLa MR cells, pretreated with UCN-01 and exposed to MNNG, undergo activation of Cdk1 and mitosis despite phosphorylation of Chk1 and inactivating phosphorylation of Cdc25c. These results indicate that UCN-01 may inhibit an alternative cell cycle arrest pathway associated with the MMR pathway that does not involve Cdc25c. In addition, recombinant hMutSalpha containing hMSH6 mutated at an N-terminal cluster of four phosphoserines exhibits decreased phosphorylation and decreased binding of hMutSalpha to G:T and O(6)meG:T. Taken together, these results suggest a model in which the amount of phosphorylated hMSH6 bound to DNA is dependent on the presence of either a DNA mismatch or DNA alkylation damage. We hypothesize that both phosphorylation of hMSH6 and total concentration of bound hMutSalpha are involved in cellular signaling of either DNA mismatch repair or MMR-dependent damage recognition activities. PMID- 21035468 TI - Aberrantly silenced promoters retain a persistent memory of the silenced state after long-term reactivation. AB - A hallmark of aberrant DNA methylation-associated silencing is reversibility. However, long-term stability of reactivated promoters has not been explored. To examine this issue, spontaneous reactivant clones were isolated from mouse embryonal carcinoma cells bearing aberrantly silenced Aprt alleles and re silencing frequencies were determined as long as three months after reactivation occurred. Despite continuous selection for expression of the reactivated Aprt alleles, exceptionally high spontaneous re-silencing frequencies were observed. A DNA methylation analysis demonstrated retention of sporadic methylation of CpG sites in a protected region of the Aprt promoter in many reactivant alleles suggesting a role for these methylated sites in the re-silencing process. In contrast, a chromatin immunoprecipitation (ChIP) analysis for methyl-H3K4, acetyl H3K9, and dimethyl-H3K9 levels failed to reveal a specific histone modification that could explain high frequency re-silencing. These results demonstrate that aberrantly silenced and reactivated promoters retain a persistent memory of having undergone the silencing process and suggest the failure to eliminate all CpG methylation as a potential contributing mechanism. PMID- 21035469 TI - Genetic variation in RPS6KA1, RPS6KA2, RPS6KB1, RPS6KB2, and PDK1 and risk of colon or rectal cancer. AB - RPS6KA1, RPS6KA2, RPS6KB1, RPS6KB2, and PDK1 are involved in several pathways central to the carcinogenic process, including regulation of cell growth, insulin, and inflammation. We evaluated genetic variation in their candidate genes to obtain a better understanding of their association with colon and rectal cancer. We used data from two population-based case-control studies of colon (n=1574 cases, 1940 controls) and rectal (n=791 cases, 999 controls) cancer. We observed genetic variation in RPS6KA1, RPS6KA2, and PRS6KB2 were associated with risk of developing colon cancer while only genetic variation in RPS6KA2 was associated with altering risk of rectal cancer. These genes also interacted significantly with other genes operating in similar mechanisms, including Akt1, FRAP1, NFkappaB1, and PIK3CA. Assessment of tumor markers indicated that these genes and this pathway may importantly contributed to CIMP+ tumors and tumors with KRAS2 mutations. Our findings implicate these candidate genes in the etiology of colon and rectal cancer and provide information on how these genes operate with other genes in the pathway. Our data further suggest that this pathway may lead to CIMP+ and KRAS2-mutated tumors. PMID- 21035471 TI - Antinociceptive effect of spirocyclopiperazinium salt compound LXM-15 via activating peripheral alpha7 nAChR and M4 mAChR in mice. AB - The aim of this study was to evaluate the antinociceptive effects and potential mechanisms of the spirocyclopiperazinium compound LXM-15. We found that LXM-15 produced significant antinociceptive effects in a dose- and time-dependent manner in mice. The maximum inhibition ratio was 70% in the acetic acid writhing test; the effect started at 1.0 h, peaked at 2.0 h with the MPEs of 61%, and persisted 3.5 h in the hot-plate test; LXM-15 reduced the time spent licking or biting the injected paw remarkably with inhibitions of 53% in formalin test. LXM-15 did not affect motor coordination, spontaneous activity, body temperature, heart rate, or liver enzyme activity, the LD(50) values was 616.26 MUmol/kg. The antinociceptive effect of LXM-15 was blocked by mecamylamine, hexamethonium, atropine or atropine methylnitrate, and was also blocked by MLA, tropicamide. In contrast, the effect was not blocked by naloxone. Meanwhile, competition receptor binding assays showed LXM-15 can bind to alpha7 nAChR or M4 mAChR. Our studies show that LXM-15 may be via activating peripheral alpha7 nicotnic and M4 muscarinic receptors, resulted in antinociceptive effects. PMID- 21035470 TI - Precancerous and non-cancer disease endpoints of chronic arsenic exposure: the level of chromosomal damage and XRCC3 T241M polymorphism. AB - Genetic variants are expected to play an important role in arsenic susceptibility. Our previous study revealed deficient DNA repair capacity to be a susceptibility factor for arsenicism. T241M polymorphism in XRCC3 (a homologous recombination repair pathway gene) is widely studied for its association with several cancers. We have investigated the association of XRCC3 T241M polymorphism with arsenic-induced precancerous and non-cancer disease outcomes. The present study evaluated the association of T241M polymorphism with arsenic-induced skin lesions, peripheral neuropathy (neurodegenerative changes), conjunctivitis and other ocular diseases. A case-control study was conducted in West Bengal, India, involving 206 cases with arsenic-induced skin lesions and 215 controls without arsenic-induced skin lesions having similar arsenic exposure. XRCC3 T241M polymorphism was determined using conventional PCR-sequencing method. Chromosomal aberration assay, arsenic-induced neuropathy and ocular diseases were also evaluated. The data revealed that presence of at least one Met allele (Met/Met or Thr/Met) was protective towards development of arsenic-induced skin lesions [OR=0.45, 95% CI: 0.30-0.67], peripheral neuropathy [OR=0.49; 95%CI: 0.30-0.82] and conjunctivitis [OR=0.60; 95%CI: 0.40-0.92]. A significant correlation was also observed between protective genotype and decreased frequency of chromosomal aberrations. Thus the results indicate the protective role of Met allele against the arsenic-induced skin lesions, chromosomal instability, peripheral neuropathy and conjunctivitis. PMID- 21035472 TI - Differential induction of adenylyl cyclase supersensitivity by antiparkinson drugs acting as agonists at dopamine D1/D2/D3 receptors vs D2/D3 receptors only: parallel observations from co-transfected human and native cerebral receptors. AB - Though there is evidence that sustained exposure of dopamine (DA) receptors to agonists can elicit a supersensitivity of adenylyl cyclase (AC), little is known about the pharmacological characteristics of this phenomenon, and possible interrelationships amongst DA receptor subtypes have not been examined. In cells co-transfected with D(1) plus D(2), or D(1) plus D(3), receptors, which are known to physically and functionally interact, long-term exposure to quinpirole, pramipexole and ropinirole (which possess negligible affinities for D(1) sites) elicited supersensitivity of D(1) receptor-activated AC. By contrast, D(2)/D(3) receptor agonists that also act as D(1) receptor agonists, bromocriptine, lisuride, cabergoline, apomorphine and DA itself, did not elicit supersensitivity. Interestingly, AC supersensitivity was also observed in the nucleus accumbens of mice pretreated with twice-daily pramipexole and quinpirole, whereas no change was seen either with lisuride or with the DA precursor, L-DOPA. Thus, AC supersensitivity is elicited by the sustained exposure of cloned human and native mouse populations of dopaminergic receptors, to D(2)/D(3) but not D(1)/D(2)/D(3) agonists. These observations may be related to the exacerbation of gambling in Parkinson's disease that is provoked by antiparkinson agents acting as selective D(2)/D(3) receptor agonists, notably pramipexole. PMID- 21035473 TI - The rise of a new GABA pharmacology. AB - Key developments in GABA pharmacology over the last 30 years are reviewed with special reference to the advances pioneered by Erminio Costa. His passion for innovative science, and his quest for novel therapies for psychiatric disorders are particularly apparent in his fundamental contributions to the field of GABA research, with a focus on anxiety disorders and schizophrenia. He was a cofounder of the GABAergic mechanism of action of benzodiazepines. He envisaged partial agonists as novel anxiolytics. He identified DBI (diazepam binding inhibitor) as endogenous agonist of neurosteroidogenesis with multiple CNS effects and he pointed to the developmental origin of GABAergic dysfunctions in schizophrenia through his discovery of a reelin deficit, all this in collaboration with Sandro Guidotti. Today, the GABA pharmacology comprises selective hypnotics, non sedative anxiolytics, memory enhancers and powerful analgesics. This article is part of a Special Issue entitled 'Trends in neuropharmacology: in memory of Erminio Costa'. PMID- 21035474 TI - Beneficial effects of an innovative exercise model on motor and oxidative disorders induced by haloperidol in rats. AB - Here we evaluate the influence of a new exercise protocol on movement disorders induced by neuroleptic drugs. In this animal model, involuntary movements are closely related to neuronal degeneration and oxidative stress (OS) that can be caused by pre-synaptic D2 receptor blockade increasing dopamine (DA) metabolism. The increase in vacuous chewing movements (VCM) and the reduced locomotor activity induced by haloperidol treatment (12 mg/kg-im, once a week for 4 weeks) was prevented by exercise, 5 times per week, which was initiated four weeks before the first haloperidol administration. Exercise training also prevented the increase of haloperidol-induced lipid peroxidation in the cortex and subcortical region and recovered the catalase activity in the subcortical region. There was a negative correlation between catalase activity in the subcortical region and the VCM frequency (r = 0.50, p < 0.05), as well as a positive correlation between VCM frequency and lipid peroxidation in the cortex (r = 0.64, p < 0.05) and subcortical region (r = 0.71, p < 0.0001). Both haloperidol and exercise increased DA uptake in the striatum, while the co-treatment (exercise plus haloperidol) reduced it. The striatal DA uptake correlated negatively with catalase activity (r = 0.51, p < 0.05), indicating a relationship between oxidative damage and the function of the transporter in the striatum. Our findings show that physical exercise can modulate dopamine uptake, especially when it is altered, and reveal the benefit of this new exercise protocol in the prevention of movement disorders related to oxidative damage. PMID- 21035475 TI - TMS over the left angular gyrus impairs the ability to discriminate left from right. AB - The underlying cognitive and neural mechanisms of the ability to discriminate left from right are hardly explored. Clinical studies from patients with impairments of left-right discrimination (LRD) and neuroimaging data suggest that the left angular gyrus is particularly involved in LRD. Moreover, it is argued that the often reported sex difference in LRD, with women being more susceptible to left-right errors than men, is the result of a stronger lateralization in men than women. Offline repetitive transcranial magnetic stimulation (rTMS) was used to test whether the left angular gyrus is involved in LRD and whether men have a stronger lateralization in LRD than women. Twenty-four participants (12 men, 12 women) completed a behavioral LRD task in three different conditions: after rTMS of the left and right angular gyrus and after 'sham' rTMS (control). The results revealed that after rTMS of the left angular gyrus, LRD accuracy rates were significantly reduced compared to the control condition. After rTMS of the right angular gyrus no difference to the control condition was observed. In addition, there was no overall sex difference in the LRD task and men and women were similarly affected by stimulation over the left and right angular gyrus, suggesting that the functional cerebral organization of LRD does not differ in men and women with similar LRD skills. Taken together, the findings suggest that the left angular gyrus is critically involved in LRD. It is argued that the left angular gyrus integrates spatial information with the meaning of the words 'left' and 'right', thereby assigning the labels 'left' and 'right' to a certain state or direction, etc. PMID- 21035478 TI - Steve Woods's contribution to research on amylin's eating inhibitory effect. AB - Amylin is secreted by pancreatic beta-cells and seems to function as a physiological signal of satiation and possibly also as an adiposity signal. Amylin's satiating effect is mediated via a direct action at area postrema (AP) neurons. The central pathways mediating amylin's effects rely on connections from the AP to the nucleus of the solitary tract and lateral parabrachial nucleus. Amylin was shown to interact, probably at the brainstem, with other satiating signals, namely cholecystokinin, glucagon-like peptide 1 and peptide YY, and other adiposity signals, namely leptin and insulin. The interaction with leptin, which is thought to involve the hypothalamus, may have important implications for the development of new and improved hormonal anti-obesity treatments. Steve Woods has contributed to the recent literature on amylin's eating inhibitory effect by some frequently cited publications. Steve's work concentrated more on the central administration of amylin and on amylin's potential role as an adiposity signal. His work will be reviewed here and discussed in the context of other important findings on amylin's role in the control of energy homeostasis. PMID- 21035476 TI - The role of Broca's area in regular past-tense morphology: an event-related potential study. AB - It has been suggested that damage to anterior regions of the left hemisphere results in a dissociation in the perception and lexical activation of past-tense forms. Specifically, in a lexical-decision task in which past-tense primes immediately precede present-tense targets, such patients demonstrate significant priming for irregular verbs (spoke-speak), but, unlike control participants, fail to do so for regular verbs (looked-look). Here, this behavioral dissociation was first confirmed in a group of eleven patients with damage to the pars opercularis (BA 44) and pars triangularis (BA 45) of the left inferior frontal gyrus (i.e., Broca's area). Two conditions containing word-onset orthographic-phonological overlap (bead-bee, barge-bar) demonstrated that the disrupted regular-verb priming was accompanied by, and covaried with, disrupted ortho-phonological priming, regardless of whether prime stimuli contained the regular inflectional rhyme pattern. Further, the dissociation between impaired regular-verb and preserved irregular-verb priming was shown to be continuous rather than categorical; priming for weak-irregular verbs (spent-spend) was intermediate in size between that of regular verbs and strong verbs. Such continuous dissociations grounded in ortho-phonological relationships between present- and past-tense forms are predicted by single-system, connectionist approaches to inflectional morphology and not predicted by current dual-system, rule-based models. Event-related potential data demonstrated that N400 priming effects were intact for both regular and irregular verbs, suggesting that the absence of significant regular-verb priming in the response time data did not result from a disruption of lexical access, and may have stemmed instead from post-lexical events such as covert articulation, segmentation strategies, and/or cognitive control. PMID- 21035477 TI - Effects of short term forced oral breathing in rat pups on weight gain, hydration and stress. AB - Nasal obstruction is a risk factor in sleep-disordered breathing with a negative impact on the quality of life in humans. We investigated hydration changes produced by short term reversible, bilateral, nasal obstruction in young developing rat pups. Physiological parameters of growth (weight gain and gastric content weight) and dehydration were analyzed during two periods; during nasal obstruction at post-natal day 8 (days 9, 11 and 13), plus 7 and 90 days after recovery of nasal breathing (day 15 and adulthood). Body weight gain in oral breathing rat pups was slower compared to controls. Gastric weight was decreased significantly only in oral breathing rat pups on days 9 and 11 while plasma osmolality and vasopressin levels increased (indicators of dehydration). There were no differences between controls and treated rat pups by day 15, or at adulthood. Short term nasal obstruction-induced forced oral breathing, decreased gastric content which had a negative impact on growth and blood glucose concentration in the short term for female rat pups. Plasma corticosterone levels increased during the dehydration but were normal in males by 90 days. This could be a model for blocked nose syndrome in the newborn. Possible long term consequences on development are discussed. PMID- 21035479 TI - Peri-saccadic mislocalization is not influenced by the predictability of the saccade target location. AB - Flashes presented around the time of a saccade are often mislocalized. The precise pattern of mislocalization is influenced by many factors. Here we study one such factor: the predictability of the saccade target's location. The experiment examines two conditions. In the first the subject makes the same horizontal rightward saccade to the same target location over and over again. In the second the subject makes saccades to a target that is jumping in unpredictable radial directions. A dot is flashed in the vicinity of the saccade target near the time of saccade onset. Subjects are asked to localize the flash by touching its location on the screen. Although various saccade parameters differed, the errors that subjects made were very similar in both conditions. We conclude that the pattern of mislocalization does not depend on the predictability of the location of the saccade target. PMID- 21035480 TI - Human blood and marrow side population stem cell and Stro-1 positive bone marrow stromal cell numbers decline with age, with an increase in quality of surviving stem cells: correlation with cytokines. AB - Hematological deficiencies increase with aging leading to anemias, reduced hematopoietic stress responses and myelodysplasias. This study tested the hypothesis that side population hematopoietic stem cells (SP-HSC) would decrease with aging, correlating with IGF-1 and IL-6 levels and increases in bone marrow fat. Marrow was obtained from the femoral head and trochanteric region of the femur at surgery for total hip replacement (N=100). Whole trabecular marrow samples were ground in a sterile mortar and pestle and cellularity and fat content determined. Marrow and blood mononuclear cells were stained with Hoechst dye and the SP-HSC profiles acquired. Marrow stromal cells (MSC) were enumerated flow cytometrically employing the Stro-1 antibody, and clonally in the colony forming unit fibroblast (CFU-F) assay. Plasma levels of IGF-1 (ng/ml) and IL-6 (pg/ml) were measured by ELISA. SP-HSC in blood and bone marrow decreased with age but the quality of the surviving stem cells increased. MSC decreased non significantly. IGF-1 levels (mean=30.7, SEM=2) decreased and IL-6 levels (mean=4.4, SEM=1) increased with age as did marrow fat (mean=1.2mmfat/g, SEM=0.04). There were no significant correlations between cytokine levels or fat and SP-HSC numbers. Stem cells appear to be progressively lost with aging and only the highest quality stem cells survive. PMID- 21035481 TI - Salidroside protects human fibroblast cells from premature senescence induced by H(2)O(2) partly through modulating oxidative status. AB - Although salidroside and salidroside-like compounds are considered as most critical constitutes needed and responsible for multiple therapeutic benefits of Rhodiola rosea L., including anti-aging, direct demonstration regarding the role of salidroside in anti-aging process is still deficient. In this study, we selected the H(2)O(2)-induced premature senescence model in human fetal lung diploid fibroblasts to investigate the protection of salidroside against aging in vitro and associated molecular mechanisms. We found that salidroside considerably reversed senescence-like phenotypes in the oxidant challenged model, including alterations of morphology, cell cycle, SA-beta-gal staining, DNA damage, as well as related molecules expression such as p53, p21 and p16. The protection occurred in a dose-dependent manner, with 5MUM offering best efficacy. The proposed antioxidant property of the compound was confirmed in this cellular system, and thus at least partially accounted for the protection of the compound against premature senescence. Similar protection of salidroside against replicative senescence was observed as well. Interestingly, the regulation of senescence related molecules by salidroside involved ROS-irrelevant mechanisms in both models. This finding presents salidroside as an attractive agent with potential to retard aging and attenuate age-related diseases in humans. PMID- 21035482 TI - Muscular laminopathies: role of prelamin A in early steps of muscle differentiation. AB - Lamin A is a nuclear envelope constituent involved in a group of human disorders, collectively referred to as laminopathies, which include Emery-Dreifuss muscular dystrophy. Because increasing evidence suggests a role of lamin A precursor in nuclear functions, we investigated the processing of prelamin A along muscle differentiation. Both protein levels and cellular localization of prelamin A appears to be modulated during C2C12 mouse myoblasts activation. Similar changes also occur in the expression of two lamin A-binding proteins: emerin and LAP2alpha. Furthermore prelamin A forms a complex with LAP2alpha in differentiating myoblasts. Prelamin A accumulation in cycling myoblasts by expressing unprocessable mutants affects LAP2alpha and PCNA amount and increases caveolin 3 mRNA and protein levels, whilst accumulation of prelamin A in differentiated muscle cells following treatment with a farnesyl transferase inhibitor inhibits caveolin 3 expression. These data provide evidence for a critical role of lamin A precursor in the early steps of muscle cell differentiation. In fact the post-translational processing of prelamin A affects caveolin 3 expression and influences the myoblast differentiation process. Thus, altered lamin A processing could affect myoblast differentiation and/or muscle regeneration and might contribute to the myopathic phenotype. PMID- 21035483 TI - Signalling via class IA PI3Ks. PMID- 21035484 TI - Targeting the cancer initiating cell: the Achilles' heel of cancer. AB - We have isolated cell with the cancer initiating cell (CIC) phenotype from PC3 cells. The PC3/(CIC) cells are more resistant than the PC3/(BC) cells to chemotherapeutic drugs such as docetaxel which is used to treat prostate cancer. Thus these prostate CICs could lay dormant and persist even after chemotherapeutic drug treatment. Then when the chemotherapeutic drug is removed, they could potentially repopulate the original tumor site or metastize to a distant site. However, the prostate CICs were not significantly more resistant to drugs which target EGFR, NF-kappaB, Smo and the natural product genistein. Interesting the prostate CICs could be rendered more sensitive to docetaxel by inclusion of suboptimal doses of genistein, cyclopamine, and EGFR inhibitors. In contrast, addition of suboptimal amounts of genistein, cyclopamine, or EGFR inhibitors did not increase the sensitivity of the PC/(BC) cells to docetaxel. Similar results were observed when combination experiments were performed with cyclopamine and suboptimal doses of either genistein or docetaxel. The BC cells are usually more rapidly proliferating than the CICs. Thus the CICs are not as sensitive to docetaxel which targets replication. In contrast, the CICs could be rendered sensitive to docetaxel or cyclopamine by co-treatment with certain other drugs, including the natural product genistein which is present in the human diet of many people, especially Asians. Genistein is by itself only weakly toxic to prostate and other cancer cells. That is probably one of the big reasons that it can be used as a dietary supplement for prostate and breast cancers. It is clear from our studies that low doses of genistein can increase the sensitivity of prostate CICs to drugs such as docetaxel and cyclopamine, two drugs either used or under consideration for prostate cancer therapy. PMID- 21035485 TI - The neutral sphingomyelinase family: identifying biochemical connections. AB - Neutral sphingomyelinases (N-SMases) are considered to be key mediators of stress induced ceramide production. The extended family of N-SMases is a subset of the DNaseI superfamily and comprises members from bacteria, yeast and mammals. In recent years, the identification and cloning of mammalian N-SMase family members has led to significant advances in understanding their physiological roles and regulation. However, there is still limited information on their regulation at the biochemical and molecular level. In this review, we summarize current knowledge about the biochemical regulation of the eukaryotic N-SMases and identify the major areas where knowledge is lacking. In recent years, research into the roles and regulation of N-SMases has moved in great strides with the cloning and characterization of multiple N-SMase isoforms and the development of knockout mice. However, as researchers continue to move forward in understanding the physiological functions of these various N-SMase isoforms, it has become exceedingly important to define howthese isoforms are regulated at the biochemical and molecular level. This is crucial for the development of future tools to study N-SMase signaling such as, for example, phospho-specific antibodies designating activation states. This is also an important part of identifying novel roles of N-SMases in physiological and pathological states. Finally, only by obtaining a more complete understanding of the workings of these enzymes at the molecular level, will investigators be able to design appropriate compounds that can target and inhibit their activity both efficiently and specifically. Certainly, the last of these is crucial when considering the potential of N-SMases as therapeutic targets. With this in mind, we sincerely hope that the next decade of research will even surpass the last ten years in advancing our understanding of the eukaryotic N-SMase family. PMID- 21035486 TI - Subtype-specific roles of phospholipase C-beta via differential interactions with PDZ domain proteins. AB - Since we first identified the PLC-beta isozyme, enormous studies have been conducted to investigate the functional roles of this protein (Min et al., 1993; Suh et al.,1988). It is now well-known that the four PLC-beta subtypes are major effector molecules in GPCR-mediated signaling, especially for intracellular Ca2+ signaling. Nonetheless, it is still poorly understood why multiple PLC-beta subtype exist. Most cells express multiple subtypes of PLC-beta in different combinations, and each subtype is involved in somewhat different signaling pathways. Therefore, studying the differential roles of each PLC-beta subtype is a very interesting issue. In this regard, we focus here on PDZ domain proteins which are novel PLC-beta interacting proteins. As scaffolders, PDZ domain proteins recruit various target proteins ranging from membrane receptors to cytoskeletal proteins to assemble highly organized signaling complexes; this can give rise to efficiency and diversity in cellular signaling. Because PLC-beta subtypes have different PDZ-binding motifs, it is possible that they are engaged with different PDZ domain proteins, and in turn participate in distinct physiological responses. To date, several PDZ domain proteins, such as the NHERF family, Shank2, and Par-3, have been reported to selectively interact with certain PLC-beta subtypes and GPCRs. Systematic predictions of potential binding partners also suggests differential binding properties between PLC-beta subtypes. Furthermore, we elucidated parallel signaling processes for multiple PLC-beta subtypes, which still perform distinct functions resulting from differential interactions with PDZ domain proteins within a single cell. Therefore, these results highlight the novel function of PDZ domain proteins as intermediaries in subtype-specific role of PLC-beta in GPCR-mediated signaling. Future studies will focus on the physiological meanings of this signaling complex formation by different PDZ domain proteins and PLC-beta subtypes. It has been observed for a long time that the expression of certain PLC-beta subtype fluctuates during diverse physiological conditions. For example, the expression of PLC-beta1 is selectively increased during myoblast and adipocyte differentiation (Faenza et al., 2004; O'Carroll et al., 2009). Likewise, PLC-beta2 is highly up-regulated during breast cancer progression and plays a critical role in cell migration and mitosis (Bertagnolo et al., 2007). Although PLC-beta3 is selectively down regulated in neuroendocrine tumors, the expression of PLC-beta1 is increased in small cell lung carcinoma (Stalberg et al., 2003; Strassheim et al., 2000). In our hypothetical model, it is most likely that up- and down regulation of certain PLC-beta subtypes are due to their selective coupling with specific GPCR-mediated signaling, implicated in these pathophysiologic conditions. Therefore, better understanding of selective coupling between PLC-beta subtypes, PDZ domain proteins, and GPCRs will shed light on new prognosis and therapy of diverse diseases, and provide potential targets for drug development. PMID- 21035487 TI - Phospholipase Cdelta3 is a novel binding partner of myosin VI and functions as anchoring of myosin VI on plasma membrane. AB - Phospholipase Cdelta3 (PLCdelta3) is a key enzyme in phosphoinositide metabolism, however, its physiological function remains unknown. Here we identified the Myosin VI (Myo6) as a binding partner of the PLCdelta3. A tail region containing IQ motif and the cargo-binding domain of Myo6, and the C2 domain and PH domain of PLCdelta3 were responsible sites for the interaction. Since Myo6 has been well analyzed as one of the "deafness genes" in mouse and human, we examined the expression pattern of PLCdelta3 mRNA in the inner ear. In situ hybridization analysis indicated that both Myo6 and PLCdelta3 were clearly and limitedly co expressed in the inner and outer hair cells in the cochlea. Although actin structure of the stereocilia of hair cells seemed to be normal and no detectable hearing defect was observed in PLCdelta3 knockout (KO) mice, stable PLCdelta3 knockdown in Caco-2 colonic carcinoma cells caused abnormal actin structure of microvilli. In addition, dramatic decrease in expression of Myo6 was observed in intestine of PLCdelta3KO mice, where microvilli structure is well developed. These results indicate that PLCdelta3 could participate in stability of microvilli structure via regulating and anchoring of Myo6 to plasma membrane. PMID- 21035488 TI - Physiology and pathology of nuclear phospholipase C beta1. AB - The existence and function of inositide signaling in the nucleus is well documented and we know that the existence of the inositide cycle inside the nucleus has a biological role. An autonomous lipid-dependent signaling system, independently regulated from its plasma membrane counterpart, acts in the nucleus and modulates cell cycle progression and differentiation.We and others focused on PLCbeta1, which is the most extensively investigated PLC isoform in the nuclear compartment. PLCbeta1 is a key player in the regulation of nuclear inositol lipid signaling, and, as discussed above, its function could also be involved in nuclear structure because it hydrolyses PtdIns(4,5)P2, a well accepted regulator of chromatin remodelling. The evidence, in a number of patients with myelodysplastic syndromes, that the mono-allelic deletion of PLCbeta1 is associated with an increased risk of developing acute myeloid leukemia paves the way for an entirely new field of investigation. Indeed the genetic defect evidenced, in addition to being a useful prognostic tool, also suggests that altered expression of this enzyme could have a role in the pathogenesis of this disease, by causing an imbalance between proliferation and apoptosis. The epigenetics of PLCbeta1 expression in MDS has been reviewed as well. PMID- 21035489 TI - Capitalizing on tumor genotyping: towards the design of mutation specific inhibitors of phosphoinsitide-3-kinase. AB - PI3Ks catalyze the phosphorylation of the inositol hydroxyls of phosphoinositide membrane components. The changes in phosphorylation of the inositides recruit proteins to the plasma membrane that initiate important signaling cascades. PI3Kalpha, one of the class IA PI3Ks, is highly mutated in cancers. All mutations analyzed result in an increase in enzymatic activity. The structures of this enzyme determined by X-ray diffraction, provide a framework for analyzing the possible structural effect of these mutations and their effect on the enzymatic activity. Many of the mutations occur at domain interfaces where they can affect domain interactions and relieve the inhibition of the wild-type enzyme by the nSH2 domain of p85. This mechanism is analogous to the mechanism of physiological activation by activated tyrosine-kinase receptors in which the phosphorylated tyrosine of the receptor (or their substrates) dislodges the nSH2 from its inhibitory position in the complex by competing with its binding to a loop in the helical domain. Other mutations in the kinase domain can directly affect the conformation of the catalytic site. One mutation, His1047Arg, uses a completely different mechanism: it changes the conformation of the C-terminal loop in such a way that it increases the interaction of the enzyme with the membrane, granting increased access to the phosphoinositide substrates. Taking advantage of the reliance of some cancers on the increased activity of mutated PI3Kalpha, will require the development of isoform-specific, mutant-specific inhibitors. The structural, biochemical and physiological data that are becoming available for PI3Ks are an important first step in this direction. PMID- 21035491 TI - Phosphoinositide signalling in the nucleus. PMID- 21035490 TI - p53 and regulation of bioactive sphingolipids. AB - Both the sphingolipid and p53 pathways are important regulators- and apparent collaborators-of cell-fate decisions. Whereas some investigations have suggested that ceramide and more complex sphingolipids function upstream of p53 or in a p53 independent manner, other studies propose that p53-dependent alterations in these sphingolipids can also contribute to apoptosis. Further studies focusing on sphingolipid metabolizing enzymes have revealed that they function similarly both upstream and downstream of p53 activation. However, whereas various components of the sphingolipid and p53 pathways may simultaneously function to elicit apoptosis and/or growth inhibition, SMase and SK1 may undergo explicit regulation by p53 that could contribute to ceramide-induced senescence in cells. Thus, we propose that regulation of bioactive sphingolipid signaling molecules could be of therapeutic benefit in the treatment of p53-dependent cancers. PMID- 21035492 TI - Involvement of human choline kinase alpha and beta in carcinogenesis: a different role in lipid metabolism and biological functions. AB - We have summarized here the importance of ChoKalpha1 in human carcinogenesis. ChoKalpha1 displays its oncogenic activity through activation of specific signaling pathways that influence on cell proliferation and survival. It is overexpressed in a large number of human tumors with an incidence of 40-60% of all tumors investigated. Currently, there is an active effort in the development of strategies to knockdown the activity of ChoKalpha through specific siRNA or small molecules inhibitors. Results from genetic silencing or from treatment with MN58b, a well characterized ChoKalpha inhibitor showing antiproliferative and antitumoral effect in mice xenografts, provide strong support to this concept, indicating that the design of new antitumoral drugs must be selective against this isoform. However, affecting the other two known isoforms of ChoK may have also therapeutic consequences since the physiologically active form of ChoK may be constituted by homo or heterodimers. Furthermore, alteration of the ChoKbeta activity might lead to a change in the lipid content of the cells of particular tissues such as skeletal muscle as described in the ChoKbeta null mice (Sher et al., 2006). Finally, the identification of the ChoKalpha1 isoform as an excellent novel tool for the diagnosis and prognosis of cancer patients may have clinical consequences of immediate usefulness. On one hand, the use of specific monoclonal antibodies against ChoKalpha1 as a tool for diagnosis in paraffin embedded samples from patient biopsies, through standard immunohistochemistry techniques, can now be achieved (Gallego-Ortega et al., 2006). On the other hand, it has been recently described the prognostic value of determination of ChoKalpha1 expression levels in non-small cell lung cancer using real time quantitative PCR technology (Ramirez de Molina et al., 2007). Therefore, further research should be supported on the utility of ChoK isoforms as a promising area to improve cancer diagnosis and treatment. PMID- 21035494 TI - Regulation of B cell survival, development and function by inositol 1,4,5 trisphosphate 3-kinase B (Itpkb). AB - In mammals, Ins(1,4,5)P3, the well known calcium mobilization messenger, is phosphorylated in the cytosol at the 3-position of the inositol ring to yield Ins(1,3,4,5)P4 by Ins(1,4,5)P3 3-kinases A, B and C isoforms as well as by inositol polyphosphate multikinase (Ipmk). Studies in gene-deficient mice have revealed that these enzymes and Ins(1,3,4,5)P4, their reaction product, play essential role in multiple physiological processes, ranging from synaptic plasticity, hematopoietic cell survival, development and function, to mRNA export, transcriptional regulation and chromatin remodelling. Rather than to provide an unique and "universal" mechanism of Ins(1,3,4,5)P4 action, these studies in genetically-modified mice point for a role of this inositide in the control of calcium mobilization, of the subcellular localisation of PH domain containing target proteins, and of higher inositol phosphate production. Mice deficient for the B isoform of inositol 1,4,5-trisphosphate 3-kinase (Itpkb) develop profound alterations in T and B cells as well as in neutrophils and mast cells. Our recent studies indicate that the 3-kinase Itpkb and Ins(1,3,4,5)P4 are important for the survival of naive mature B cells and the control of proapoptotic Bim protein expression, rather than for the control of B cell transition from one developmental stage to another. They also suggest that Itpkb is an important component in the control of B cell anergy. PMID- 21035493 TI - Diphosphoinositol polyphosphates: what are the mechanisms? AB - In countries where adulthood is considered to be attained at age eighteen, 2011 can be the point at which the diphosphoinositol polyphosphates might formally be described as "coming of age", since these molecules were first fully defined in 1993 (Menniti et al., 1993; Stephens et al., 1993b). But from a biological perspective, these polyphosphates cannot quite be considered to have matured into the status of being independently-acting intracellular signals. This review has discussed several of the published proposals for mechanisms by which the diphosphoinositol polyphosphates might act. We have argued that all of these hypotheses need further development.We also still do not know a single molecular mechanism by which a change in the levels of a particular diphosphoinositol polyphosphate can be controlled. Yet, despite all these gaps in our understanding, there is an enduring anticipation that these molecules have great potential in the signaling field. Reflecting our expectations of all teenagers, it should be our earnest hope that in the near future the diphosphoinositol polyphosphates will finally grow up. PMID- 21035495 TI - Hits, Fhits and Nits: beyond enzymatic function. AB - We have briefly summarized what is known about these proteins, but in closing wish to feature the outstanding questions. Hint1 was discovered mistakenly as an inhibitor of Protein Kinase C and designated Pkci, a designation that still confuses the literature. The other Hint family members were discovered by homology to Hint1. Aprataxin was discovered as a result of the hunt for a gene responsible for AOA1. Fhit was discovered through cloning of a familial chromosome translocation breakpoint on chromosome 3 that interrupts the large FHIT gene within an intron, in the FRA3B chromosome region (Ohta et al., 1996), now known to be the region of the human genome most susceptible to DNA damage due to replication stress (Durkin et al., 2008). The NitFhit fusion genewas discovered during searches for Fhit homologs in flies and worms because the fly/worm Nit polypeptide is fused to the 5'-end of the Fhit gene; the mammalian Nit gene family was discovered because of the NitFhit fusion gene, in searches for homologs to the Nit polypeptide of the NitFhit gene. Each of the Hit family member proteins is reported to have enzymatic activities toward putative substrates involving nucleosides or dinucleosides. Most surprisingly, each of the Hit family proteins discussed has been implicated in important DNA damage response pathways and/or tumor suppression pathways. And for each of them it has been difficult to assign definite substrates, to know if the substrates and catalytic products have biological functions, to know if that function is related to the DNA damage response and suppressor functions, and to precisely define the pathways through which tumor suppression occurs. When the fly Nit sequence was found at the 5'-end of the fly Fhit gene, this gene was hailed as a Rosetta stone gene/protein that would help in discovery of the function of Fhit, because the Nit protein should be in the same signal pathway (Pace et al., 2000). However, the mammalian Nit family proteins have turned out to be at least as mysterious as the Fhit proteins, with the Nit1 substrate still unknown and the surprising finding that Nit proteins also appear to behave as tumor suppressor proteins. Whether the predicted enzymatic functions of these proteins are relevant to the observed biological functions, remain among the outstanding unanswered puzzles and raise the question: have these mammalian proteins evolved beyond the putative original enzymatic purpose, such that the catalytic function is now vestigial and subservient to signal pathways that use the protein-substrate complexes in pathways that signal apoptosis or DNA damage response? Or can these proteins be fulfilling catalytic functions independently but in parallel with signal pathway functions, as perhaps observed for Aprataxin? Or is the catalytic function indeed part of the observed biological functions, such as apoptosis and tumor suppression? Perhaps the recent, post-genomic focus on metabolomics and genome wide investigations of signal pathway networks will lead to answers to some of these outstanding questions. PMID- 21035496 TI - Leukotriene B4 receptors: novel roles in immunological regulations. AB - Mammals have at least two receptors for LTB4; high-affinity BLT1 and low-affinity BLT2, both of which are GPCRs. 12-HHT serves as a more potent and abundant ligand for BLT2 than LTB4. BLT1 is expressed in a variety of inflammatory and immune cells including granulocytes, eosinophils, macrophages, differentiated Th1, Th2 and Th17 cells, effecter CD8+ T cells, dendritic cells and osteoclasts. BLT1 antagonists will be beneficial for the treatment of various diseases such as bronchial asthma, multiple sclerosis, contact dermatitis, and postmenopausal osteoporosis. BLT2 plays different roles from BLT1, and one important role of BLT2 is the maintenance of mucosal integrity in the colon. PMID- 21035497 TI - Deciphering the signaling pathways of cancer stem cells of glioblastoma multiforme: role of Akt/mTOR and MAPK pathways. AB - These findings emphasize that the mTOR pathway may contribute to maintenance of quiescence of CSCs, and provide a basis for manipulating CSCs in the treatment of GBM. Future research should focus on further defining the PI3K/Akt/mTOR molecular network in the regulation of stem cell quiescence and provide rationale for targeting the cancer-initiating cells of GBM. PMID- 21035498 TI - The signaling role of inositol hexakisphosphate kinases (IP6Ks). AB - The past ten years have seen a contained explosion of interest in inositol pyrophosphates. The early cloning of the IP6Ks and the more recent identification of the PP-IP5Ks have allowed the development of essential experimental tools to investigate the physiological role of inositol pyrophosphates. However, for this exciting field of research to gain momentum, simpler and more reliable research protocols need to be further developed. The ability to resolve and quantify inositol pyrophosphates using gel electrophoresis (Losito et al., 2009) has dramatically altered the way we are studying this class of molecules, opening new avenues for research. The use of this technology to resolve, detect and characterize inositol pyrophosphates extracted from cells certainly represents one desirable aim. The most crucial objective, however, is to obtain definite proof of the new mechanism of post-translational modification by identifying with biophysical methods the presence in vivo of pyrophosphorylated serines. This will hopefully precipitate the development of new ways to detect this modification, for example through the production of antibodies that specifically recognize pyrophosphorylated serines. PMID- 21035499 TI - The mechanism of contribution of integrin linked kinase (ILK) to epithelial mesenchymal transition (EMT). AB - Integrin linked kinase (ILK) is ubiquitously expressed serine/threonine protein kinase, a binding partner of beta1 and beta3 integrin subunit as a cytoplasmic effector of integrin receptors that functionally links them to the actin cytoskeleton.We postulate that ILK is important enzyme involved in epithelial mesenchymal transition (EMT) a critical event in the process of cancer progression. Commonly used EMT molecular markers include among others increased expression of N-cadherin and vimentin, nuclear localization of beta-catenin, and the decrease of E-cadherin synthesis. In this study we were able to show that N cadherin expression in melanoma cells is dependent on ILK signaling and the translocation of beta-catenin to the nucleus. Silencing of ILK expression by siRNA significantly inhibited the stabilization and subsequent nuclear translocation of beta-catenin and the expression of N-cadherin, a crucial molecule in the EMT, which facilitates association with fibroblast and endothelial cells during invasion of various cancers. The results allow to cautiously speculate on the important role of ILK in the cross-talk between integrins and cadherins accompanying EMT in melanoma. PMID- 21035500 TI - Regulation and roles of PI3Kbeta, a major actor in platelet signaling and functions. AB - Phosphoinositide 3-kinases (PI3Ks) are important signaling enzymes involved in the regulation of a number of critical cell functions. Significant progress has been made during the last few years in defining the implication of individual PI3K isoforms. The role of the class IA PI3Kbeta in different cell types has only been recently uncovered by the use of isoform-selective inhibitors and the development of mouse models harboring p110beta catalytic subunit knock-out or germline knock-in of a kinase-dead allele of p110beta. Although it is classically admitted that class IA PI3Ks are activated by receptor tyrosine kinases through recruitment of the regulatory subunits to specific tyrosine phosphorylated motifs via their SH2 domains, PI3Kbeta is activated downstream of G protein-coupled receptors, and by co-operation between heterotrimeric G proteins and tyrosine kinases. PI3Kbeta has been extensively studied in platelets where it appears to play an important role downstream of ITAM signaling, G protein-coupled receptors and aIIbbeta3 integrin. Accordingly, mouse exhibiting p110beta inactivation selectively in megakaryocyte/platelets are resistant to thromboembolism induced by carotid injury. The present review summarizes recent data concerning the mechanisms of PI3Kbeta regulation and the roles of this PI3K isoform in blood platelet functions and other cell types. PMID- 21035502 TI - Synthesis and characterization of poly(3-hydroxyalkanoates) from Brassica carinata oil with high content of erucic acid and from very long chain fatty acids. AB - Pseudomonas aeruginosa produced medium chain length poly(3-hydroxyalkanoates) (mcl-PHAs) when grown on substrates containing very long chain fatty acids (VLCFA, C>20). Looking for low cost carbon sources, we tested Brassica carinata oil (erucic acid content 35-48%) as an intact triglyceride containing VLCFA. Oleic (C18:1), erucic (C22:1), and nervonic (C24:1) acids were also employed for mcl-PHA production as model substrates. The polymers obtained were analyzed by GC of methanolyzed samples, GPC, 1H and 13C NMR, ESI MS of partially pyrolyzed samples, and DSC. The repeating units of such polymers were saturated and unsaturated, with a higher content of the latter in the case of the PHA obtained from B. carinata oil. Statistical analysis of the ion intensity in the ESI mass spectra showed that the PHAs from pure fatty acids are random copolymers, while the PHA from B. carinata oil is either a pure polymer or a mixture of polymers. Weight-average molecular weight varied from ca. 56,000 g/mol for the PHA from B. carinata oil and oleic acid, to about 120,000 g/mol for those from erucic and nervonic acids. The PHAs from erucic and nervonic acids were partially crystalline, with rubbery characteristics and a melting point (Tm) of 50 degrees C, while the PHAs from oleic acid and from B. carinata oil afforded totally amorphous materials, with glass transition temperatures (Tg) of -52 degrees C and -47 degrees C, respectively. PMID- 21035501 TI - The impact of PTEN regulation by CK2 on PI3K-dependent signaling and leukemia cell survival. AB - Gene alterations affecting elements of PI3K signaling pathway do not appear to be sufficient to explain the extremely high frequency of PI3K signaling hyperactivation in leukemia. It has been known for long that PTEN phosphorylation at the C-terminal tail, in particular by CK2, contributes to the stabilization and simultaneous inhibition of this critical tumor suppressor. However, direct evidence of the involvement of this mechanism in cancer has been gathered only recently. It is now known that CK2-mediated posttranslational, non-deleting, inactivation of PTEN occurs in T-ALL, CLL and probably other leukemias and solid tumors. To explore this knowledge for therapeutic purposes remains one of the challenges ahead. PMID- 21035503 TI - Quaternary complexes composed of plasmid DNA/protamine/fish sperm DNA/stearic acid grafted chitosan oligosaccharide micelles for gene delivery. AB - Quaternary complexes with condensed core of plasmid DNA, protamine, fish sperm DNA and shell of stearic acid grafted chitosan oligosaccharide (CSO-SA), were prepared. The CSO-SA could self-assemble to form nano-sized micelles in aqueous solution and demonstrated excellent internalization ability of tumor cells. Dynamic light scattering (DLS) measurement and transmission electrostatic microscope (TEM) images showed that quaternary complexes had spherical shape with about 25 nm number average diameter, and the size of quaternary complexes was smaller than that of CSO-SA micelles and CSO-SA micelles/plasmid DNA binary complexes. The transfection efficiencies of quaternary complexes on HEK293 and MCF-7 cells increased with incubation time, and were significantly higher than that of CSO-SA micelles/plasmid DNA binary complexes. The optimal transfection efficiency of quaternary complexes on HEK293 and MCF-7 cells measured by flow cytometer after 96 h was 23.82% and 41.43%, respectively. Whereas, the transfection efficiency of LipofectamineTM 2000 on HEK293 and MCF-7 cells after 96 h was 32.45% and 33.23%, respectively. The data of luciferease activity measurement showed that the optimal ratio of plasmid DNA:fish sperm DNA:protamine:CSO-SA was 1:1:5:5. The results indicated that the present quaternary complexes were potential non-viral gene delivery system. PMID- 21035504 TI - Injection-molded nanocomposites and materials based on wheat gluten. AB - This is, to our knowledge, the first study of the injection molding of materials where wheat gluten (WG) is the main component. In addition to a plasticizer (glycerol), 5 wt.% natural montmorillonite clay was added. X-ray indicated intercalated clay and transmission electron microscopy indicated locally good clay platelet dispersion. Prior to feeding into the injection molder, the material was first compression molded into plates and pelletized. The filling of the circular mold via the central gate was characterized by a divergent flow yielding, in general, a stronger and stiffer material in the circumferential direction. It was observed that 20-30 wt.% glycerol yielded the best combination of processability and mechanical properties. The clay yielded improved processability, plate homogeneity and tensile stiffness. IR spectroscopy and protein solubility indicated that the injection molding process yielded a highly aggregated structure. The overall conclusion was that injection molding is a very promising method for producing WG objects. PMID- 21035505 TI - Discovery of an unusual alternative splicing pathway of the immunoglobulin heavy chain in a teleost fish, Danio rerio. AB - In present study, we identified a novel membrane immunoglobulin M isotype from zebrafish (Danio rerio), which was designated as mIgM-2, adding a new member to the Immunoglobulin family in teleost fish. The full length of cloned mIgM-2 cDNA was 611 bp, encoding 150 amino acids. The putative mIgM-2 protein sequence consists of one constant region and a trans-membrane region. Phylogenetic analysis showed that mIgM-2 grouped with the known zebrafish IgM sequences. The mIgM-2 mRNA was widely expressed in immune-related tissues including intestine, kidney and skin. In vivo stimulation with LPS significantly up-regulates the expression of mIgM-2. Our results will add new insight into the immunoglobulin class diversity of teleost fish, and to better understand the evolutionary history of adaptive immunity from fish to mammals as a whole. PMID- 21035506 TI - Endothelial and cardiac progenitors: boosting, conditioning and (re)programming for cardiovascular repair. AB - Preclinical studies performed in cell culture and animal systems have shown the outstanding ability of stem cells to repair ischemic heart and lower limbs by promoting the formation of new blood vessels and new myocytes. In contrast, clinical studies of stem cell administration in patients with myocardial ischemia have revealed only modest, although promising, results. Basic investigations have shown the feasibility of adult cells reprogramming into pluripotent cells by defined factors, thus opening the way to the devise of protocols to ex vivo derive virtually unexhausted cellular pools. In contrast, cellular and molecular studies have indicated that risk factors limit adult-derived stem cell survival, proliferation and engraftment in ischemic tissues. The use of fully reprogrammed cells raises safety concerns; therefore, adult cells remain a primary option for clinicians interested in therapeutic cardiovascular repair. Pharmacologic approaches have been devised to restore the cardiovascular repair ability of failing progenitors from patients at risk. In the present contribution, the most advanced pharmacologic approaches to (re)program, boost, and condition endothelial and cardiac progenitor cells to enhance cardiovascular regeneration are discussed. PMID- 21035507 TI - A novel sarsasapogenin glycoside from Asparagus racemosus elicits protective immune responses against HBsAg. AB - The aim of the present investigation was to evaluate the adjuvant potential of a novel sarsasapogenin glycoside (immunoside) isolated from Asparagus racemosus in combination with hepatitis B surface antigen (HBsAg). Various in vitro and animal derived protocols were used to determine the response of immunoside adjuvanted with HBsAg and the results were compared with alum adjuvanted with HBsAg. Several biomarkers such as antibody titre (IgG, IgG1/IgG2a) were measured in mice sera. Cell proliferation, cytokines (IL-2, IFN-gamma and IL-4), and lymphocyte sub populations (CD4/CD8, CD3 and CD19) were determined in splenocytes from mice administered subcutaneously with test substances. In these cells CD4/CD8 derived IFN-gamma release was also determined. Macrophage preparations were used for the determination of IL-12, IFN-gamma and nitrite content. Seroconversion potential was compared with a standard vaccine. Acute safety evaluation of immunoside was done in mice. Effect of immunoside on red blood cell haemolysis was determined. The results have suggested that immunoside potentially enhanced anti-HBsAg immune response via augmenting Th1/Th2 response in a dose dependent manner. PMID- 21035509 TI - How multiple repetitions influence the processing of self-, famous and unknown names and faces: an ERP study. AB - Because we live in an extremely complex social environment, people require the ability to memorize hundreds or thousands of social stimuli. The aim of this study was to investigate the effect of multiple repetitions on the processing of names and faces varying in terms of pre-experimental familiarity. We measured both behavioral and electrophysiological responses to self-, famous and unknown names and faces in three phases of the experiment (in every phase, each type of stimuli was repeated a pre-determined number of times). We found that the negative brain potential in posterior scalp sites observed approximately 170 ms after the stimulus onset (N170) was insensitive to pre-experimental familiarity but showed slight enhancement with each repetition. The negative wave in the inferior-temporal regions observed at approximately 250 ms (N250) was affected by both pre-experimental (famous>unknown) and intra-experimental familiarity (the more repetitions, the larger N250). In addition, N170 and N250 for names were larger in the left inferior-temporal region, whereas right-hemispheric or bilateral patterns of activity for faces were observed. The subsequent presentations of famous and unknown names and faces were also associated with higher amplitudes of the positive waveform in the central-parietal sites analyzed in the 320-900 ms time-window (P300). In contrast, P300 remained unchanged after the subsequent presentations of self-name and self-face. Moreover, the P300 for unknown faces grew more quickly than for unknown names. The latter suggests that the process of learning faces is more effective than learning names, possibly because faces carry more semantic information. PMID- 21035508 TI - An insertional trap for conditional gene expression in Toxoplasma gondii: identification of TAF250 as an essential gene. AB - Toxoplasmosis is characterized by fast lytic replication cycles leading to severe tissue lesions. Successful host cell invasion is essential for pathogenesis. The division cycle of Toxoplasma gondii is characterized by an unusual cell cycle progression and a distinct internal budding mechanism. To identify essential genes involved in the lytic cycle we devised an insertional gene trapping strategy using the Tet-transactivator system. In essence, a random, active promoter is displaced with a tetracycline regulatable promoter, which if in an essential gene, will result in a conditionally lethal phenotype upon tetracycline addition. We isolated eight mutants with growth defects, two of which displayed modest invasion defects, one of which had an additional cell cycle defect. The trapped loci were identified using expression microarrays, exploiting the tetracycline dependent expression of the trapped genes. In mutant 3.3H6 we identified TCP-1, a component of the chaperonin protein folding machinery under the control of the Tet promoter. However, this gene was not critical for growth of mutant 3.3H6. Subsequently, we identified a suppressor gene encoding a protein with a hypothetical function by guided cosmid complementation. In mutant 4.3B13, we identified TAF250, an RNA polymerase II complex component, as the trapped, essential gene. Furthermore, by mapping the plasmid insertion boundaries we identified multiple genomic rearrangements, which hint at a potential replication dependent DNA repair mechanism. Furthermore, these rearrangements provide an explanation for inconsistent locus rescue results observed by molecular biological approaches. Taken together, we have added an approach to identify and study essential genes in Toxoplasma. PMID- 21035510 TI - Cell microcarriers and microcapsules of stimuli-responsive polymers. AB - Cell microcarriers and microcapsules have presented a wide range of potential applications. This article overviews their role in biotechnology with focus on the progress accomplished using stimuli-responsive polymers. Key properties of cell microcarriers and microcapsules are identified, followed by a description of the chemistry and gel formation mechanism of some of the stimuli-responsive polymers used to design them. Production methods are introduced and characterization techniques for evaluating such microsystems are equally presented. PMID- 21035511 TI - A nanofibrous sheet-based system for linear delivery of nifedipine. AB - We developed a nanofibrous sheet-based system to achieve linear release of nifedipine for oral delivery. The nanofibrous sheets of micro-porosity were fabricated by the electrospinning method, using a biocompatible polymer, poly (lactic-co-glycolic acid). The sheets were then used as a drug diffusion barrier by capping and sealing a compressed tablet, composed of nifedipine and a solubility enhancer, polyvinylpyrrolidone. The nanofibrous sheets of different thicknesses were prepared to vary the rate of drug diffusion in this work. In vitro drug release study revealed that as the sheet thickness increased, drug release was more retarded, where a lag phase of drug release became more evident. We were to realize linear drug release by combining two distinctly capped tablets, each showing a different drug release, which exhibited an almost linear release of nifedipine during 24h (R(2)>0.986). The drug release profile was not influenced by the pH of the release media as the morphological structure of nanofibrous sheets was seen to be not very different at both pHs 1.2 and 6.8. Therefore, we conclude that a combination of two tablets, each capped with nanofibrous sheets of different thickness, is a promising system for linear delivery of oral drug. PMID- 21035512 TI - Transport of epidermal growth factor in the stroke-injured brain. AB - Stroke is a neurological disorder that currently has no cure. Intrathecal delivery of growth factors, specifically recombinant human epidermal growth factor (rhEGF), stimulates endogenous neural precursor cells in the subventricular zone (SVZ) and promotes tissue regeneration in animal models of stroke. In this model, rhEGF is delivered with an invasive minipump/catheter system, which causes trauma to the brain. A less invasive strategy is to deliver rhEGF from the brain cortex; however, this requires the protein to diffuse through the brain, from the site of injection to the SVZ. Although this method of delivery has great potential, diffusion is limited by rapid removal from the extracellular space and hence for successful translation into the clinic strategies are needed to increase the diffusion distance. Using integrative optical imaging we investigate diffusion of rhEGF vs. poly(ethylene glycol) modified rhEGF (PEG-rhEGF) in brain slices of both uninjured and stroke-injured animals. For the first time, we quantitatively show that PEG modification reduces the rate of growth factor elimination by over an order of magnitude. For rhEGF this corresponds to a two to threefold increase in predicted brain penetration distance, which we confirm with in vivo data. PMID- 21035514 TI - 7-ketocholesterol induces apoptosis in differentiated PC12 cells via reactive oxygen species-dependent activation of NF-kappaB and Akt pathways. AB - Cholesterol oxidation products formed under the enhanced oxidative stress in the brain are suggested to induce neuronal cell death. However, it is still unknown whether oxysterol-induced apoptosis in neuronal cells is mediated by Akt and NF kappaB pathways. We assessed the apoptotic effect of 7-ketocholesterol against differentiated PC12 cells in relation to activation of the reactive oxygen species-dependent nuclear factor (NF)-kappaB, which is mediated by the Akt pathway. 7-Ketocholesterol induced a decrease in cytosolic Bid and Bcl-2 levels, increase in cytosolic Bax levels, cytochrome c release, caspase-3 activation and upregulation of p53. 7-Ketocholesterol induced an increase in phosphorylated inhibitory kappaB-alpha, NF-kappaB p65 and NF-kappaB p50 levels, binding of NF kappaB p65 to DNA, and activation of Akt. Treatment with Bay 11-7085 (an inhibitor of NF-kappaB activation) and oxidant scavengers, including N acetylcysteine, prevented the 7-ketocholesterol-induced formation of reactive oxygen species, activation of NF-kappaB, Akt and apoptosis-related proteins, and cell death. Results from this study suggest that 7-ketocholesterol may exert an apoptotic effect against PC12 cells by inducing activation of the caspase-8 dependent pathway as well as activation of the mitochondria-mediated cell death pathway, leading to activation of caspases, via the reactive oxygen species dependent activation of NF-kappaB, which is mediated by the Akt pathway. PMID- 21035515 TI - Human Vdelta1-T cells regulate immune responses by targeting autologous immature dendritic cells. AB - Recent studies suggest that tissue resident Vdelta1-T cells may downregulate immune responses in human beings. However, the function of peripheral blood Vdelta1-T cells and their mechanisms of action remain largely unknown because of their limited numbers and the difficulties encountered in expanding these cells. In this study, we provide direct evidence demonstrating that peripheral human Vdelta1-T cells can abrogate adaptive immune responses by direct killing of autologous dendritic cells through a perforin-mediated pathway. These findings advance our basic understanding of this unique T-cell subset. PMID- 21035513 TI - Impact of exercise and dietary fatty acid composition from a high-fat diet on markers of hunger and satiety. AB - To compare the effects of both dietary fatty acid composition and exercise vs. sedentary conditions on circulating levels of hunger and satiety hormones. Eight healthy males were randomized in a 2 * 2 crossover design. The four treatments were 3 days of HF diets (50% of energy) containing high saturated fat (22% of energy) with exercise (SE) or sedentary (SS) conditions, and high monounsaturated fat (30% of energy) with exercise (UE) or sedentary (US) conditions. Cycling exercise was completed at 45% of VO(2)max for 2h daily. On the third HF day, 20 blood samples were drawn over a 24h period for each hormone (leptin, insulin, ghrelin, and peptide YY (PYY)). A visual analog scale (VAS) was completed hourly between 0800 and 2200. Average 24h leptin and insulin levels were lower while 24h PYY was higher during exercise vs. sedentary conditions. FA composition did not differentially affect 24h hormone values. VAS scores for hunger and fullness did not differ between any treatment but did correlate with ghrelin, leptin, and insulin. High saturated or unsaturated fat diets did not differ with respect to markers of hunger or satiety. Exercise decreased 24h leptin and insulin while increasing PYY regardless of FA composition. PMID- 21035516 TI - Evaluation of three different scoring systems for dental erosion: a comparative study in adolescents. AB - OBJECTIVES: The purpose of the study was to evaluate and compare three scoring systems for dental erosion representing different approaches: the recently proposed Basic Erosive Wear Examination (B.E.W.E.), the Simplified Tooth Wear Index (S-T.W.I.), and the Evaluating Index of Dental Erosion (EV.I.D.E.), which are introduced and calibrated in the present study, in order to contribute to the development of a standardised and validated erosion index. METHODS: A cross sectional study was conducted, in which a random and stratified sample of 502 adolescents aged 14-16 years was examined using the aforementioned scoring systems. RESULTS: A significant number of Greek adolescents had experienced dental erosion: 58%, 51.6% and 45.2%, according to the B.E.W.E., S-T.W.I. and EV.I.D.E. scores, respectively. Additionally, 22.7-24.3% of the subjects had lesions into dentine (according to the EV.I.D.E. and S-T.W.I. scores respectively), whereas the B.E.W.E. classified all subjects with erosion in the "none" and "low" risk level categories. However, the use of the B.E.W.E. cumulative scores was important for avoiding the overestimation of the prevalence of erosion. The aetiological criteria of the EV.I.D.E. seemed to reduce the false positive cases. CONCLUSIONS: The S-T.W.I. appeared to have the lowest content validity, while the B.E.W.E. was a convenient to use index, with sufficient sensitivity and specificity. Nevertheless, the B.E.W.E. cut-off values have to be reconsidered in order to reflect the severity of the erosive lesions. The B.E.W.E. could also be supplemented with a group of sufficient validated aetiological criteria, which are necessary to establish a more accurate differential diagnosis of dental erosion. PMID- 21035517 TI - Adjunctive use of an anti-oxidant agent to improve resistance of hybrid layers to degradation. AB - OBJECTIVE: To determine the role of an anti-oxidant agent (ascorbic acid-AA) on resin-dentin bonds resistance to degradation of two adhesives. METHODS: Flat dentin surfaces from 48 human molars were bonded as per manufacturer's instructions with: a two-step etch-and-rinse self-priming adhesive (Single Bond SB) and a two-step self-etch adhesive (Clearfil SE Bond-CSE). Half of the specimens were bonded with the same adhesives, but after the addition of 10% AA into their formulation. Resin composite build-ups were constructed incrementally and sectioned into resin-dentin beams (1.0mm(2)) that were stored under four conditions: (1) water immersion for 24h; (2) water immersion for 1 year; (3) water immersion for 4 years; and (4) chemical challenging (immersion in 10% NaOCl for 5 h). Beams were pulled to failure in tension at 0.5mm/min. Mean microtensile bond strength (MTBS) data were analysed with ANOVA and multiple comparisons tests (P<0.05). Analysis of debonded dentin beams was performed by scanning electron microscopy (SEM). RESULTS: After 24 h, SB and CSE performed equally, regardless of AA incorporation. Inclusion of AA on CSE formulation decreased MTBS following one-year water storage, but maintained SB bond strength values even after four years of water storage. NaOCl challenge diminished MTBS for both adhesives, but when AA was added to SB, this reduction was significantly lower. CONCLUSIONS: The inclusion of AA on adhesive's formulation exerts a protective role on resin dentin bonds resistance to degradation when SB is used. Bonding durability of CSE may be compromised by the addition of sodium ascorbate. PMID- 21035518 TI - Reciprocity phase in various 2*2 games by agents equipped with two-memory length strategy encouraged by grouping for interaction and adaptation. AB - This paper numerically investigates 2*2 games involving the Prisoner's Dilemma, Chicken, Hero, Leader, Stag Hunt, and Trivial Games in which agents have a strategy expressed by five-bit, two-memory length. Our motivation is to explore how grouping for game interaction and strategy adaptation influence ST reciprocity and R reciprocity (Tanimoto and Sagara, 2007a [Tanimoto, J., Sagara, H., 2007a. A study on emergence of coordinated alternating reciprocity in a 2*2 game with 2-memory length strategy. Biosystems 90(3), 728-737]. Enhanced R reciprocity is observed with the stronger grouping for game interaction when a relatively stronger grouping for strategy adaptation is assumed. On the other hand, enhanced ST reciprocity emerged with the stronger grouping for strategy adaptation when the relatively weaker grouping for game interaction is imposed. Our numerical experiment deals with those two groupings independently and dependently. PMID- 21035519 TI - Leptin receptor activation increases Sam68 tyrosine phosphorylation and expression in human trophoblastic cells. AB - Leptin is produced in placenta where it has been found to be an important autocrine signal for trophoblastic growth during pregnancy, promoting antiapoptotic and trophic effects. Leptin receptor is present in trophoblastic cells and leptin may fully activate signaling. We have previously implicated the RNA-binding protein Sam68 in leptin signal transduction in immune cells. In the present work, we have studied the possible role of Sam68 in leptin receptor signaling in trophoblastic cells (JEG-3 cells). Leptin dose-dependently stimulated Sam68 phosphorylation in JEG-3 cells, as assessed by immunoprecipitation and immunoblot with anti-phosphotyrosine antibodies. As previously observed in other systems, tyrosine phosphorylation of Sam68 in response to leptin inhibits its RNA binding capacity. Besides, leptin stimulation dose-dependently increases Sam68 expression in JEG-3 cells, as assessed by quantitative PCR. Consistently, the amount of Sam68 protein is increased after 24h of leptin stimulation of trophoblastic cells. In order to study the possible role of Sam68 on leptin receptor synthesis, we employed antisense strategy to knockdown the expression of Sam68. We have found that a decrease in Sam68 expression leads to a decrease in leptin receptor amount in JEG-3 cells, as assessed both by quantitative PCR and immunoblot. These results strongly suggest the participation of Sam68 in leptin receptor signaling in human trophoblastic cells, and therefore, Sam68 may mediate some of the leptin effects in placenta. PMID- 21035520 TI - Interplay of cAMP and MAPK pathways in hCG secretion and fusogenic gene expression in a trophoblast cell line. AB - Differentiation of human placental mononuclear trophoblasts into a multinucleate syncytium involves up-regulation of key proteins promoting cell fusion and increased capacity for placental hormonogenesis. It is well established that the activation of adenylyl cyclase leads to increased expression of trophoblast fusogenic gene machinery and human chorionic gonadotropin (hCG) secretion. We used the forskolin-induced syncytialisation of BeWo choriocarcinoma cells as a model to characterise in detail the signalling pathway downstream of adenylyl cyclase. Forskolin treatment induced a rapid and potent ERK1/2 and p38MAPK phosphorylation; this cascade required PKA-AKAP interactions and led to downstream CREB-1/ATF-1 phosphorylation via ERK1/2-dependent but p38MAPK independent mechanisms. Interestingly both p38MAPK and ERK1/2 were involved in forskolin-induced hCG-secretion, suggesting the presence of additional p38MAPK dependent but CREB-1/ATF-1-independent pathways. Forskolin treatment of BeWo cells significantly up-regulated the expression of various fusogenic gene mRNAs, including syncytin-1 and -2 (by 3- and 10-fold, respectively) the transcription factors old astrocyte specifically induced substance (OASIS) and glial cells missing a (GCMa) (by 3- and 6-fold, respectively) and the syncytin-2 receptor, major facilitator superfamily domain containing 2 (MFSD2) (by 2-fold). Up regulation of AKAP79 and AKAP250 (by 2.5- and 4-fold, respectively) was also identified in forskolin-treated BeWo cells. Forskolin effects on all these genes were suppressed by chemical inhibition of p38MAPK whereas only specific genes were sensitive to ERK1/2 inhibition. This data provide novel insights into the signalling molecules and mechanisms regulating fusogenic gene expression by the adenylyl cyclase pathway. PMID- 21035521 TI - Nicotine enhances contextual fear memory reconsolidation in rats. AB - There is increasing evidence that nicotine is involved in learning and memory. However, there remains no study that has explored the relationship between nicotine and memory reconsolidation. At present study, we tested the effects of nicotine on the reconsolidation of contextual fear memory in rats. Behavior procedure involved four training phases: habituation (Day 0), fear conditioning (Day 1), reactivation (Day 2) and test (Day 3). Rats were injected saline or nicotine (0.25, 0.5 and 1.0mg/kg) immediately after reactivation. Percent of time spent freezing was used to measure conditioned fear response. Results showed that compared with saline rats, rats with nicotine at 1.0mg/kg presented a significant increase of freezing response on Day 3. Nicotine at 1.0mg/kg was ineffective when injected 6h after reactivation. Further results showed that the enhancement of freezing response induced by nicotine at 1.0mg/kg was dependent on fear memory reconsolidation, and was not attributed to an enhancement of the nonspecific freezing response 24h after nicotine administration. The results suggest that nicotine administration immediately after reactivation enhances contextual fear memory reconsolidation. Our present finding extends previous research on the nicotinic effects on learning and memory. PMID- 21035522 TI - Complementary synaptic distribution of enzymes responsible for synthesis and inactivation of the endocannabinoid 2-arachidonoylglycerol in the human hippocampus. AB - Clinical and experimental evidence demonstrates that endocannabinoids play either beneficial or adverse roles in many neurological and psychiatric disorders. Their medical significance may be best explained by the emerging concept that endocannabinoids are essential modulators of synaptic transmission throughout the central nervous system. However, the precise molecular architecture of the endocannabinoid signaling machinery in the human brain remains elusive. To address this issue, we investigated the synaptic distribution of metabolic enzymes for the most abundant endocannabinoid molecule, 2-arachidonoylglycerol (2 AG), in the postmortem human hippocampus. Immunostaining for diacylglycerol lipase-alpha (DGL-alpha), the main synthesizing enzyme of 2-AG, resulted in a laminar pattern corresponding to the termination zones of glutamatergic pathways. The highest density of DGL-alpha-immunostaining was observed in strata radiatum and oriens of the cornu ammonis and in the inner third of stratum moleculare of the dentate gyrus. At higher magnification, DGL-alpha-immunopositive puncta were distributed throughout the neuropil outlining the immunonegative main dendrites of pyramidal and granule cells. Electron microscopic analysis revealed that this pattern was due to the accumulation of DGL-alpha in dendritic spine heads. Similar DGL-alpha-immunostaining pattern was also found in hippocampi of wild type, but not of DGL-alpha knockout mice. Using two independent antibodies developed against monoacylglycerol lipase (MGL), the predominant enzyme inactivating 2-AG, immunostaining also revealed a laminar and punctate staining pattern. However, as observed previously in rodent hippocampus, MGL was enriched in axon terminals instead of postsynaptic structures at the ultrastructural level. Taken together, these findings demonstrate the post- and presynaptic segregation of primary enzymes responsible for synthesis and elimination of 2-AG, respectively, in the human hippocampus. Thus, molecular architecture of the endocannabinoid signaling machinery supports retrograde regulation of synaptic activity, and its similar blueprint in rodents and humans further indicates that 2-AG's physiological role as a negative feed-back signal is an evolutionarily conserved feature of excitatory synapses. PMID- 21035523 TI - Neural heterogeneities influence envelope and temporal coding at the sensory periphery. AB - Peripheral sensory neurons respond to stimuli containing a wide range of spatio temporal frequencies. We investigated electroreceptor neuron coding in the gymnotiform wave-type weakly electric fish Apteronotus leptorhynchus. Previous studies used low to mid temporal frequencies (<256 Hz) and showed that electroreceptor neuron responses to sensory stimuli could be almost exclusively accounted for by linear models, thereby implying a rate code. We instead used temporal frequencies up to 425 Hz, which is in the upper behaviorally relevant range for this species. We show that electroreceptors can: (A) respond up to the highest frequencies tested and (B) display strong nonlinearities in their responses to such stimuli. These nonlinearities were manifested by the fact that the responses to repeated presentations of the same stimulus were coherent at temporal frequencies outside of those contained in the stimulus waveform. Specifically, these consisted of low frequencies corresponding to the time varying contrast or envelope of the stimulus as well as higher harmonics of the frequencies contained in the stimulus. Heterogeneities in the afferent population influenced nonlinear coding as afferents with the lowest baseline firing rates tended to display the strongest nonlinear responses. To understand the link between afferent heterogeneity and nonlinear responsiveness, we used a phenomenological mathematical model of electrosensory afferents. Varying a single parameter in the model was sufficient to account for the variability seen in our experimental data and yielded a prediction: nonlinear responses to the envelope and at higher harmonics are both due to afferents with lower baseline firing rates displaying greater degrees of rectification in their responses. This prediction was verified experimentally as we found that the coherence between the half-wave rectified stimulus and the response resembled the coherence between the responses to repeated presentations of the stimulus in our dataset. This result shows that rectification cannot only give rise to responses to low frequency envelopes but also at frequencies that are higher than those contained in the stimulus. The latter result implies that information is contained in the fine temporal structure of electroreceptor afferent spike trains. Our results show that heterogeneities in peripheral neuronal populations can have dramatic consequences on the nature of the neural code. PMID- 21035524 TI - Endothelin as a neuroprotective factor in the olfactory epithelium. AB - In mammals, the olfactory sensory neurons are the only ones directly in contact with an aggressive environment. Thus, the olfactory mucosa is one of the few neuronal zones which are continuously renewed during adulthood. We have previously shown that endothelin is locally matured in the olfactory mucosa and that olfactory sensory neurons preferentially express ETB receptors, while ETA receptors are rather present in non neuronal olfactory mucosa cells. In addition to its vasoactive effect, the endothelin system is known for its pleiotropic effects including the modulation of cell population dynamics. We thus examined its potential neuroprotective effect in the olfactory mucosa using a primary culture of olfactory sensory neurons lying on non neuronal cells. While a serum deprivation led to a massive decrease of the density of olfactory sensory neurons in the primary cultures, endothelin 1 (ET-1) rescued part of the neuronal population through both ETA and ETB receptors. This effect was mainly anti apoptotic as it reduced cleaved caspase-3 signal and nuclear condensation. Furthermore, the olfactory epithelium of ETB-deficient rats displayed increased apoptosis. These results strongly suggest that ET-1 acts as an anti-apoptotic factor on olfactory sensory neurons, directly through ETB and indirectly by limiting non neuronal cells death through ETA. PMID- 21035525 TI - Pre-operative vestibular pattern and balance compensation after vestibular schwannoma surgery. AB - This longitudinal study aimed to assess the sensorimotor balance strategies before and after vestibular schwannoma (VS) surgery according to the degree of pre-operative vestibular lesion. Thirty-eight VS patients were split in three groups according to caloric vestibular test results before surgery; nine had a symmetrical vestibular response (vestibular normoreflexy), 19 with a decreased response of more than 20% of the affected side (vestibular hyporeflexy) and 10 with an absent caloric response on the side of the affected labyrinth (vestibular areflexy). They underwent pendular rotary vestibular testing (RVT), allowing to evaluate gain and directional preponderance of the vestibulo-ocular reflex, and a sensory organisation test (SOT), evaluating balance control in six conditions (C1 to C6). These tests were performed shortly before, and 8 and 90 days after surgery. Directional preponderance performances of patients with vestibular normoreflexy or hyporeflexy followed a classical time-course with a huge asymmetry just after surgery and a recovery to pre-operative performances at 90 days; patients with vestibular areflexy were relatively stable in time. Variation in SOT performances of patients with vestibular normoreflexy, especially in the more complex C4 to C6, followed a classical time-course with an important postural degradation just after surgery and a recovery to pre-operative performances at 90 days. Patients with vestibular areflexy showed no balance degradation just after surgery and a marked increase in performances at 90 days after surgery, especially in C5 and C6. Performances of patients with vestibular hyporeflexy were intermediate, close to performances of patients with vestibular normoreflexy before surgery and close to performances of patients with vestibular areflexy at 8 and 90 days after surgery. Pre-operative vestibular function alteration triggers an adaptive process, characterized by a restoration of the symmetry of the vestibular nuclei activity and by sensory substitution and new behavioural strategies, allowing the anticipation of unilateral vestibular deafferentation effects. PMID- 21035526 TI - Circulating microRNAs, possible indicators of progress of rat hepatocarcinogenesis from early stages. AB - MicroRNAs (miRNAs), a class of small noncoding RNAs that regulate gene expression at the posttranscriptional level, are believed promising biomarkers for several diseases as well as a novel target of drugs, including cancer. In particular, miRNAs might allow detection of early stages of carcinogenesis. The present study was conducted to provide concrete evidence using chemical-induced hepatocarcinogenesis in rat as a model. We thereby observed aberrant fluctuation of circulating miRNAs in the serum of rats not only with neoplastic lesions such as hepatocellular adenoma (HCA) and hepatocellular carcinoma (HCC), but also with preneoplastic lesions, such as foci of hepatocellular alteration (FHA). Additional qRT-PCR analysis revealed gradual elevation of some circulating miRNAs (i.e., let-7a, let-7f, miR-34a, miR-98, miR-331, miR-338 and miR-652) with progress of hepatocarcinogenesis. Interestingly, increased levels of let-7a, let 7f and miR-98 were statistically significant even in the serum of rats at very early stages. These findings provide the first evidences that circulating miRNAs have the potential to predict carcinogenesis at earlier stages, preneoplastic lesions than with previous biomarkers and that they might be utilized to monitor the progress of tumor development. PMID- 21035527 TI - Human volunteer studies investigating the potential for toxicokinetic interactions between the pesticides deltamethrin; pirimicarb and chlorpyrifos methyl following oral exposure at the acceptable daily intake. AB - Human volunteer studies have been conducted by orally administering the pesticides deltamethrin (0.01 mg/kg/day) or pirimicarb (0.02 mg/kg/day) at the acceptable daily intake (ADI) together with chlorpyrifos-methyl (0.01 mg/kg/day), in order to investigate any potential interactions that may occur during dietary exposure. Deltamethrin and pirimicarb are metabolised in vivo by hydrolytic enzymes, which may be susceptible to inhibition by esterase-inhibiting compounds, such as chlorpyrifos-methyl. Urine samples were collected at time points up to at least 48 h post-exposure and metabolites were quantified. Urinary metabolite excretion data obtained from the mixed exposures were compared with data obtained from the same individuals given a dose of each individual pesticide on a separate occasion. Metabolite excretion profiles for both pesticides administered as a mixed dose with chlorpyrifos-methyl were qualitatively similar to those obtained for the individual doses. Peak excretion of deltamethrin and pirimicarb metabolites occurred at around 4h post-exposure for both the individual and the mixed exposure scenarios, and metabolite excretion was almost complete within 24h. No statistically significant differences were found between the individual and mixed doses for either metabolite excretion half-life or metabolite levels quantified in 24-h total urine collections. The data presented here indicate that no significant toxicokinetic interactions occur between either deltamethrin or pirimicarb and chlorpyrifos-methyl when orally administered together at the ADI. PMID- 21035528 TI - In vitro detoxification of cyclosarin (GF) by modified cyclodextrins. AB - Developing potent detoxification strategies for prophylaxis and therapy against organophosphate (OP) intoxication still represents a challenging task. Clinical application of numerous investigated substances including enzymes and low molecular scavengers like metal ions or nucleophiles could not yet be realised due to profound disadvantages. Presenting a promising attempt, cyclodextrins (CDs) efficiently enhance the degradation of some organophosphorus compounds. The present study examined the in vitro GF degradation mediated by three CDs and a nucleophilic precursor performed by mass spectrometric detection with ammonia chemical ionisation. All four compounds caused a notable enhancement of GF detoxification that was synergistically accelerated in the case of 2-O-(3-carboxy 4-iodosobenzyl)-beta-cyclodextrin (IBA-beta-CD) with the alpha-nucleophile 2 iodosobenzoic acid (IBA) grafted on the secondary face of beta-cyclodextrin (beta CD). In vitro toxicokinetic investigations of CD derivatives are needed to evaluate the effect of slow terminal elimination phase of the more toxic (-)-GF shown for two CD-derivatives underlining the necessity of detecting the complete kinetic course of inactivation. The observed effect of fast high affinity binding (20-30%) represents an additional therapeutic option of an extremely rapid reduction of GF concentration in vivo. Distinctive differences in the course of reaction are detected depending on beta-CD-derivatives, allowing a first inference of possible mechanisms and relevance of attached substituents. However, further profound investigation needs to be done to evaluate the basis of a clinical application of substituted CDs as potential detoxification agents. PMID- 21035529 TI - In line NIR quantification of film thickness on pharmaceutical pellets during a fluid bed coating process. AB - Along with the risk-based approach, process analytical technology (PAT) has emerged as one of the key elements to fully implement QbD (quality-by-design). Near-infrared (NIR) spectroscopy has been extensively applied as an in-line/on line analytical tool in biomedical and chemical industries. In this study, the film thickness on pharmaceutical pellets was examined for quantification using in line NIR spectroscopy during a fluid-bed coating process. A precise monitoring of coating thickness and its prediction with a suitable control strategy is crucial to the quality assurance of solid dosage forms including dissolution characteristics. Pellets of a test formulation were manufactured and coated in a fluid-bed by spraying a hydroxypropyl methylcellulose (HPMC) coating solution. NIR spectra were acquired via a fiber-optic probe during the coating process, followed by multivariate analysis utilizing partial least squares (PLS) calibration models. The actual coating thickness of pellets was measured by two separate methods, confocal laser scanning microscopy (CLSM) and laser diffraction particle size analysis (LD-PSA). Both characterization methods gave superb correlation results, and all determination coefficient (R(2)) values exceeded 0.995. In addition, a prediction coating experiment for 70min demonstrated that the end-point can be accurately designated via NIR in-line monitoring with appropriate calibration models. In conclusion, our approach combining in-line NIR monitoring with CLSM and LD-PSA can be applied as an effective PAT tool for fluid bed pellet coating processes. PMID- 21035530 TI - Preparation and characterization of water-soluble albumin-bound curcumin nanoparticles with improved antitumor activity. AB - Curcumin (CCM), a yellow natural polyphenol extracted from turmeric (Curcuma longa), has potent anti-cancer properties as has been demonstrated in various human cancer cells. However, the widespread clinical application of this efficient agent in cancer and other diseases has been limited by its poor aqueous solubility and bioavailability. In this study, we prepared novel CCM-loaded human serum albumin (HSA) nanoparticles (CCM-HSA-NPs) for intravenous administration using albumin bound technology. Field emission scanning electron microscopy (FE SEM) and dynamic light scattering (DLS) investigation confirmed a narrow size distribution in the 130-150nm range. Furthermore, CCM-HSA-NPs showed much greater water solubility (300-fold) than free CCM, and on storage, the biological activity of CCM-HSA-NPs was preserved with negligible activity loss. In vivo distributions and vascular endothelial cells transport studies demonstrated the superiority of CCM-HSA-NPs over CCM. Amounts of CCM in tumors after treatment with CCM-HSA-NPs were about 14 times higher at 1h after injection than that achieved by CCM. Furthermore, vascular endothelial cell binding of CCM increased 5.5-fold, and transport of CCM across a vascular endothelial cell monolayer by Transwell testing was 7.7-fold greater for CCM-HSA-NPs than CCM. Finally, in vivo antitumor tests revealed that CCM-HSA-NPs (10 or 20mg/kg) had a greater therapeutic effect (50% or 66% tumor growth inhibition vs. PBS-treated controls) than CCM (18% inhibition vs. controls) in tumor xenograft HCT116 models without inducing toxicity. We attribute this potent antitumor activity of CCM-HSA-NPs to enhanced water solubility, increased accumulation in tumors, and an ability to traverse vascular endothelial cell. PMID- 21035531 TI - Polyphenols-rich Vernonia amygdalina shows anti-diabetic effects in streptozotocin-induced diabetic rats. AB - AIM OF THE STUDY: This study aims to investigate the hypoglycemic properties of Vernonia amygdalina Del. (VA) and its possible mechanisms of action in a single dose STZ induced diabetic rat model. MATERIALS AND METHODS: A dose-response study was conducted to determine optimum dose for the hypoglycemic effect of VA in STZ induced diabetic rats. The optimum dose (400 mg/kg) was used throughout the 28 day chronic study. Body weight, food and water intakes of the rats were monitored daily. Fasting blood serum, pancreas, liver and soleus muscle were collected for biochemical analyses. Chemical composition of VA was analysed using HPLC and LC ESI-MS. RESULTS: The study reveals that ethanolic extract of VA contains high level of polyphenols mainly 1,5-dicaffeoyl-quinic acid, dicaffeoyl-quinic acid, chlorogenic acid and luteolin-7-O-glucoside. In an oral glucose tolerance test, 400 mg/kg VA exhibited a significant improvement in glucose tolerance of the STZ induced diabetic rats. 28-day treatment with 400 mg/kg VA resulted in 32.1% decrease in fasting blood glucose compared to diabetic control. VA also caused significant decrease (18.2% and 41%) in triglyceride and total cholesterol level. Besides, VA showed protective effect over pancreatic beta-cells against STZ induced damage, causing a slight increase in insulin level compared to diabetic control. VA administration also showed positive regulation of the antioxidant system, both enzymatic and non-enzymatic. Furthermore, VA was found to increase expression of GLUT 4 (24%) in rat skeletal muscle. Further tissue fractionation revealed that it can increase the GLUT 4 translocation (35.7%) to plasma membrane as well, suggesting that VA may stimulate skeletal muscle's glucose uptake. This observation is in line with the restoration in skeletal muscle glycogenesis of VA treated group. However, no alteration was observed in GLUT 1 expression. In addition, VA also suppressed (40% inhibition) one of the key hepatic gluconeogenic enzymes, glucose-6-phosphatase (G6Pase). CONCLUSIONS: VA possesses antihyperglycemic effect, most probably through increasing GLUT 4 translocation and inhibiting hepatic G6Pase. The polyphenols in the extract may be the candidates that are responsible for the above-mentioned biological activities. PMID- 21035533 TI - Normal and delayed wound healing is improved by sesamol, an active constituent of Sesamum indicum (L.) in albino rats. AB - ETHNO-PHARMACOLOGICAL RELEVANCE: The seeds of Sesamum indicum Linn. (Pedaliaceae) has been used traditionally for the treatment of wounds in Buldhana district of Maharashtra state. Sesamol is the main anti-oxidative constituent contained mainly in the processed sesame seed oil which has not been explored scientifically for its wound healing activity. AIM OF THE STUDY: To investigate the influence of sesamol (SM) on wound repair, both in normal and dexamethasone (DM) delayed healing processes in albino rats. MATERIALS AND METHODS: Incision, excision and dead space wounds were inflicted on albino rats (180-220 g) of either sex, under ketamine anaesthesia. Group I served as control, group II received SM 50 mg/kg i.p., group III was treated with dexamethasone (DM) i.m. (0.17 mg/kg) and SM+DM was given to group IV. The tensile strength, wound contraction, hydroxyproline, lysyl oxidase and total RNA and DNA levels (in granulation tissue) were measured. RESULTS: The tensile strength significantly (p<0.05) increased with SM at 471.40+/-14.66 g when compared to control at 300.60+/-9.16 g in normal and DM suppressed healing. No significant change was observed in duration of wound contraction and lysyl oxidase when compared to control at 2.98+/-0.10 mg. SM treated rats showed a significant (p<0.05) rise in hydroxyproline levels at 6.45+/-0.45 mg when compared to control at 1.75+/-0.20 mg. CONCLUSION: These results indicate that sesamol could be a promising drug in normal as well as delayed wound healing processes. PMID- 21035532 TI - Inhibitory effects of Cinnamomum cassia extract on atopic dermatitis-like skin lesions induced by mite antigen in NC/Nga mice. AB - AIM OF THE STUDY: Cinnamomum cassia (C. cassia) has been traditionally used to treat allergic disease as well as dyspepsia, gastritis, and blood circulation disturbances. However, the antiallergic properties of C. cassia have not been fully verified using scientific tools. This study investigated the effectiveness of C. cassia extract (CCE) as an antiallergic agent in atopic dermatitis model and underlying mechanism. MATERIALS AND METHODS: The effect of CCE on mite antigen-treated NC/Nga mice was evaluated by examining skin symptom severity, levels of serum IgE, tumor necrosis factor-alpha (TNF-alpha), and histamine, skin histology, and mRNA expression of cytokines in the skin lesions. Moreover, the effect of CCE on TNF-alpha-and interferon-gamma (IFN-gamma)-induced chemokine production in human keratinocytes was investigated using ELISA. RESULTS: CCE treatment of NC/Nga mice reduced the dermatitis score and the levels of serum IgE, histamine, and TNF-alpha. Histological examination showed inhibition of the thickening of the epidermis/dermis and reduced dermal infiltration of inflammatory cells. In skin lesions, mRNA expression of IL-4, TNF-alpha, and thymus and activation-regulated chemokine (TARC) was inhibited by CCE treatment. The production of TARC, macrophage-derived chemokine, and RANTES from IFN-gamma and TNF-alpha-stimulated human keratinocytes was suppressed by CCE treatment in a dose-dependent manner. CONCLUSIONS: CCE inhibits the development of atopic dermatitis-like skin lesions in NC/Nga mice by suppressing the T-helper 2 cell response. PMID- 21035534 TI - Immunostimulatory effects of Uncaria perrottetii (A. Rich.) Merr. (Rubiaceae) vinebark aqueous extract in Balb/C mice. AB - AIMS OF THE STUDY: Crude extract of Uncaria perrottetii (A. Rich.) Merr. vinebark was evaluated for its immunomodulating activity in Balb/C mice. Initially, the immunomodulatory potential of the plant extract was evaluated using in vitro immune response assays at different concentrations of the plant extract (10 MUg/mL, 20 MUg/mL, 50 MUg/mL and 100 MUg/mL). Using the optimum concentration determined in the in vitro assays, the protective effect of the plant extract was assessed against drug-induced immunosuppression in vivo. MATERIALS AND METHODS: For the in vivo experiment, thirty-six (36) mice were divided into 3 groups of 12 mice each: (1) cyclophosphamide drug-induced (30 mg/kg BW) immunosuppressed mice (Cy group) served as the positive control; (2) Uncaria perrottetii extract and Cy treated mice (U+Cy); and (3) PBS-injected mice as the negative control group [(-) CTRL]. RESULTS: The optimum concentration was determined to be 50 MUg/mL in the in vitro assays. At this concentration, Uncaria perrottetii extract stimulated peritoneal phagocyte activation, produced a significant increase in the activity of phagocytic cells from the spleen and promoted splenic cellular proliferation with or without lipopolysaccharide (LPS) when compared with the PBS-treated cells (negative control). Moreover, cells treated with 50 MUg/mL of Uncaria perrottetii increased macrophage respiratory burst activity that was comparable to that of the phorbol myristate acetate-stimulated splenic macrophages. In all immune assays undertaken in the in vivo experiment, the Cy-treated mice showed significantly lower response when compared with the PBS-treated mice. Significant improvement in peritoneal cell activation, phagocytic activity and cellular proliferation was exhibited by the U+Cy-treated mice when compared with Cy injected mice. The extract from Uncaria perrottetii also significantly enhanced respiratory burst and plasma lysozyme activity compared with the Cy-injected mice. CONCLUSIONS: Based on the results of both in vitro and in vivo trials, Uncaria perrottetii extract has immunopotentiating activities on the innate immunity of Balb/C mice and the extract could potentially reverse the immunosuppressive effects of Cy. However, the potential of the plant as source of bioactive products and metabolites for drug development still has to be fully investigated. PMID- 21035535 TI - Comparison of rhesus and cynomolgus macaques in a Streptococcus pyogenes infection model for vaccine evaluation. AB - Animal models predictive of human disease are generally difficult to establish and reproduce. In the case of the Group A Streptococcus (GAS) bacterium, which is predominantly a human pathogen, virulence assessment in animal models is problematic. We compared a monkey colonization and pharyngitis model of infection in two macaque species to determine the optimal model for vaccine candidate evaluation. Rhesus and cynomolgus macaques were intranasally infected with a streptomycin resistant (Str(r)) GAS strain. Monkeys were monitored for body weight and temperature changes, throat swabs and sera were collected, and clinical observations were noted throughout the study. Both species exhibited oropharyngeal colonization by GAS, with rhesus macaques demonstrating a more sustained colonization through day 28 post-challenge. Veterinary observations revealed no significant differences between GAS-infected rhesus and cynomolgus macaques. Mock-infected monkeys did not exhibit clinical symptoms or GAS colonization throughout the study. ELISA results demonstrated that both rhesus and cynomolgus macaques developed anti-streptolysin-O antibody titers, with cynomolgus generating higher titers. Sera from infected monkeys produced opsonophagocytic killing and bound to the bacterium in an immunofluorescence assay. Both rhesus and cynomolgus macaques can be used for colonization studies with this GAS M3 strain, yet only mild clinical signs of pharyngitis and tonsillitis were observed. PMID- 21035536 TI - Identification of Mycobacterium tuberculosis genes preferentially expressed during human infection. AB - The identification of Mycobacterium tuberculosis genes, specifically expressed during infection is a key step in understanding molecular mechanism of mycobacterial pathogenesis. Such genes likely encode proteins required for mycobacterium's survival and progressive infection within the host. In this study, we applied in-vivo-induced antigen technology (IVIAT) to M. tuberculosis and identified 11 putative in-vivo induced genes encoding for immunogenic proteins of diverse functions; these included transcriptional regulators (Rv1460 and Rv2565), biosynthesis and macromolecule metabolism (leuD, guaB1, plcC, hupB and glyS), polyketide synthases (pks6 and pks9), cell processes (ctpA) and one with unknown function (Rv3701c). Quantitative real time-PCR analysis of these genes in the specimens obtained from TB patients demonstrated induced expression of eight genes as compared with bacteria grown in-vitro. In addition, distribution of these genes in different strains of M. tuberculosis was analyzed using PCR and their nucleotide sequence alignments and they were found to be widely distributed among M. tuberculosis isolates including multiple-drug resistant (MDR) and extensively-drug resistant (XDR). This study identified several antigenic determinants of M. tuberculosis expressed during infection, which might help pathogens adapt to or counter hostile environments and suggesting their role during disease process. PMID- 21035537 TI - Effect of iodine on early stage thyroid autonomy. AB - Thyroid autonomy is a frequent cause of thyrotoxicosis in regions with iodine deficiency. Epidemiological data suggest that iodide may influence the course of pre-existing thyroid autonomy. Making use of FRTL-5 cells stably expressing a constitutively activating TSH receptor mutation as an in vitro model of thyroid autonomy, we investigated the impact of iodide on proliferation, function and changes in global gene expression. We demonstrate that iodine inhibits growth in TSHR WT and L629F mutant FRTL-5 cells and downregulates e.g. protocadherin cluster (Pcdha1-13) and thyroid responsive element (Thrsp). In addition functional genes e.g. iodotyrosine deiodinase (iyd) and oncogen junB are upregulated, while sodium-iodide-symporter (Nis) and thyroid peroxidase (Tpo) are downregulated by iodide. Iodide tunes down the biological activity of autonomous thyrocytes and may thus be of therapeutic benefit not only to prevent the occurrence of somatic TSHR mutations, causing thyroid autonomy, but also to slow down the development of clinically relevant disease. PMID- 21035538 TI - Genome-wide identification of genes that play a role in boron stress response in yeast. AB - Boron is an essential micronutrient for plants and it is either necessary or beneficial for animals. Studies identified only few genes related to boron metabolism thus far and details of how boron is imported into cells and used in cell metabolism are largely unknown. In order to identify genes that play roles in boron metabolism, we screened the entire set of yeast haploid deletion mutants and identified 6 mutants that were resistant to toxic levels of boron, and 21 mutants that were highly sensitive to boron treatment. Furthermore, we performed a proteomic approach to identify additional proteins that are significantly up regulated by boron treatment. Our results revealed many genes and pathways related to boron stress response and suggest a possible link between boron toxicity and translational control. PMID- 21035539 TI - Prenatal Programming and Toxicity II (PPTOX II): role of environmental stressors in the developmental origins of disease. PMID- 21035540 TI - Silver exposure in developing zebrafish produces persistent synaptic and behavioral changes. AB - Environmental silver exposures are increasing due to the use of silver nanoparticles, which exert antimicrobial actions by releasing Ag+, a suspected developmental neurotoxicant. We evaluated the long-term neurochemical and behavioral effects of embryonic Ag+ exposure in zebrafish at concentrations that had no overt effects on morphological development. Exposure to 0.03, 0.1 or 0.3 MUM Ag+ during the first five days post-fertilization caused elevations in both dopamine and serotonin turnover in the adult zebrafish brain without affecting basal neurotransmitter levels. Consistent with these synaptic effects, Ag+ exposed fish showed a faster acquisition of avoidance behavior in a three-chamber test apparatus, without any change in response latency or overall swimming ability. Our results indicate that Ag+ is a developmental neurotoxicant that causes persistent neurobehavioral effects, reinforcing health concerns about Ag+ released from silver nanoparticles. PMID- 21035541 TI - The many ways of coping with pressure. AB - The current paper reviews strategies employed by microorganisms from the deep biosphere, especially piezophiles (from the greek piezo = to press and philo = love), to cope with high hydrostatic pressure (HHP) prevailing in these biotopes. The aim of this review is not to constitute an exhaustive report of our current knowledge on the physiology of piezophiles, as recent reviews have covered part of this subject in detail (Abe, 2007; Lauro and Bartlett, 2008; Michiels et al., 2008; Simonato et al., 2006). Rather, we illustrate here, via a few chosen examples, where we stand in our understanding of the mechanisms employed by microorganisms from the depths of our planet to cope with HHP. PMID- 21035542 TI - Growing insights into the safety of bacteriocins: the case of enterocin S37. AB - Very few studies have been reported on the cytotoxicity and impact of bacteriocins, and especially enterocins, upon eukaryotic cells. In order to gain more information on the safety of bacteriocins, we focused this study on enterocin S37, a bacteriocin produced by Enterococcus faecalis S37. We observed dose-dependent cytotoxicity toward undifferentiated Caco-2/TC7 cells. Moreover, no significant effect on differentiated monolayer Caco-2/TC7 and no apoptotic features were observed when cells were treated with 10 MUg/ml of enterocin S37. The results obtained indicate possible safe use of enterocin S37 in the gastrointestinal tract of animals to prevent pathogen invasion and/or infection. PMID- 21035543 TI - Identification of outer membrane proteins of Vibrio parahaemolyticus and Vibrio alginolyticus altered in response to gamma-irradiation or long-term starvation. AB - Vibrio parahaemolyticus and Vibrio alginolyticus were subjected to gamma irradiation (0.5 kGy) or starvation by incubation for 8 months in seawater to study modifications in their outer membrane protein patterns. After treatment, outer membrane protein profiles of starved or gamma-irradiated bacteria were found to be altered when analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Altered proteins were identified by mass spectrometry (MS and MS/MS) and analyses revealed that OmpU can be considered a starvation stress-induced protein. In addition, expression of OtnA, OmpW, OmpA and peptidoglycan-associated lipoprotein decreased to non-detectable levels in starved cells. Furthermore, MltA-interacting protein MipA appeared under gamma irradiation or starvation conditions. Thus, it can be considered to be a gamma irradiation, long-term starvation stress protein in some vibrios. PMID- 21035544 TI - Cloning and characterization of a p-cymene monooxygenase from Pseudomonas chlororaphis subsp. aureofaciens. AB - p-Cymene monooxygenase is the enzyme system that catalyzes the hydroxylation of p cymene to 4-isopropylbenzyl alcohol (p-cumic alcohol), the initial step in the assimilation of p-cymene by Pseudomonas chlororaphis subsp. aureofaciens. Cloning and sequencing of single NADH-dependent cytochrome c reductase gene (cymA) present in P. chlororaphis subsp. aureofaciens was described earlier. In this study, analysis of the upstream sequence of cymA revealed two open reading frames, designated as cymB (495 bp) and cymM (1128 bp). Database searches with the cymM gene product showed similarity to integral-membrane di-iron enzymes, while that with cymB showed no significant similarity to other known proteins with the exception of epoxystyrene isomerases. Expression of all three components (cymMBA) in Escherichia coli confirmed its ability for p-cymene methyl group hydroxylation, while expression of cymM and cymA along with the partially truncated cymB gene showed an 85% decrease in the hydroxylation capacity. Our results suggest for the first time that the small protein, CymB, having no conserved domains in protein databases, is involved as enhancer/activator in p cymene hydroxylation. PMID- 21035545 TI - The 4th European Spores Conference, Cortona (Italy), May 27-29, 2010. PMID- 21035546 TI - Features of Bacillus cereus swarm cells. AB - When propagated on solid surfaces, Bacillus cereus can produce differentiated swarm cells under a wide range of growth conditions. This behavioural versatility is ecologically relevant, since it allows this bacterium to adapt swarming to environmental changes. Swarming by B. cereus is medically important: swarm cells are more virulent and particularly prone to invade host tissues. Characterisation of swarming-deficient mutants highlights that flagellar genes as well as genes governing different metabolic pathways are involved in swarm-cell differentiation. In this review, the environmental and genetic requirements for swarming and the role played by swarm cells in the virulence this pathogen exerts will be outlined. PMID- 21035547 TI - Behavioural assessments of neurotoxic effects and neurodegeneration in zebrafish. AB - Altered neurological function will generally be behaviourally apparent. Many of the behavioural models pioneered in mammalian models are portable to zebrafish. Tests are available to capture alterations in basic motor function, changes associated with exteroceptive and interoceptive sensory cues, and alterations in learning and memory performance. Excepting some endpoints involving learning, behavioural tests can be carried out at 4 days post fertilization. Given larvae can be reared quickly and in large numbers, and that software solutions are readily available from multiple vendors to automatically test behavioural responses in 96 larvae simultaneously, zebrafish are a potent and rapid model for screening neurological impairments. Coupling current and emerging behavioural endpoints with molecular techniques will permit and accelerate the determination of the mechanisms behind neurotoxicity and degeneration, as well as provide numerous means to test remedial drugs and other therapies. The emphasis of this review is to highlight unexplored/underutilized behavioural assays for future studies. This article is part of a Special Issue entitled Zebrafish Models of Neurological Diseases. PMID- 21035548 TI - An ecdysone receptor from the pentatomomorphan, Nezara viridula, shows similar affinities for moulting hormones makisterone A and 20-hydroxyecdysone. AB - It has been suggested that Pentatomomorpha utilise the C(28) ecdysteroid, makisterone A (MakA), as the major moulting hormone rather than the more common C(27) hormone, 20-hydroxyecdsyone (20E). The present study is the first to examine this postulate at the level of the ecdysone receptor protein, a heterodimer of nuclear receptors EcR and USP. cDNAs encoding two alternatively spliced isoforms of EcR and a single USP were isolated from a high-quality cDNA library prepared from a representative pentatomomorphan, Nezara viridula (Nv). NvEcR and NvUSP were found to group phylogenetically with heteropteran and other insect EcRs and USP/RXRs, respectively. Sequence comparison and phylogenetic analysis of these proteins found them to be distinct from those belonging to other hemipteran ecdysone receptors characterised to date. Co-expression of the His(6)-tagged ligand binding regions (LBRs) of the two NvEcR variants with the FLAG-tagged LBR of NvUSP was achieved in insect cells employing appropriately constructed baculoviruses. The corresponding heterodimers, designated NvE10 and NvE11, were purified by affinity chromatography utilising the His(6) tags on their NvEcR subunits. The heterodimers displayed nanomolar affinity for [(3)H]ponasterone A (K(d) = 6.8-7.5 nM), characteristic of ecdysone receptors. MakA has a similar affinity to 20E for both NvE10 and NvE11, consistent with MakA being a major moulting hormone in N. viridula. PMID- 21035550 TI - Improved drug targeting of cancer cells by utilizing actively targetable folic acid-conjugated albumin nanospheres. AB - Folic acid-conjugated albumin nanospheres (FA-AN) have been developed to provide an actively targetable drug delivery system for improved drug targeting of cancer cells with reduced side effects. The nanospheres were prepared by conjugating folic acid onto the surface of albumin nanospheres using 1-ethyl-3-(3 dimethylaminopropyl) carbodiimide (EDAC) as a catalyst. To test the efficacy of these nanospheres as a potential delivery platform, doxorubicin-loaded albumin nanospheres (DOX-AN) and doxorubicin-loaded FA-AN (FA-DOX-AN) were prepared by entrapping DOX (an anthracycline, antibiotic drug widely used in cancer chemotherapy that works by intercalating DNA) into AN and FA-AN nanoparticles. Cell uptake of the DOX was then measured. The results show that FA-AN was incorporated into HeLa cells (tumor cells) only after 2.0h incubation, whereas HeLa cells failed to incorporate albumin nanospheres without conjugated folic acid after 4.0h incubation. When HeLa cells were treated with the DOX-AN, FA-DOX AN nanoparticles or free DOX, cell viability decreased with increasing culture time (i.e. cell death increases with time) over a 70h period. Cell viability was always the lowest for free DOX followed by FA-DOX-AN4 and then DOX-AN. In a second set of experiments, HeLa cells washed to remove excess DOX after an initial incubation for 2h were incubated for 70h. The corresponding cell viability was slightly higher when the cells were treated with FA-DOX-AN or free DOX whilst cells treated with DOX-AN nanoparticles remained viable. The above experiments were repeated for non-cancerous, aortic smooth muscle cells (AoSMC). As expected, cell viability of the HeLa cells (with FA receptor alpha, FRalpha) and AoSMC cells (without FRalpha) decreased rapidly with time in the presence of free DOX, but treatment with FA-DOX-AN resulted in selective killing of the tumor cells. These results indicated that FA-AN may be used as a promising actively targetable drug delivery system to improve drug targeting to cancer cells. PMID- 21035549 TI - The small GTPase Rheb is a key component linking amino acid signaling and TOR in the nutritional pathway that controls mosquito egg development. AB - Mosquitoes transmit numerous devastating human diseases because they require blood feeding for egg development. Previously, we have shown that the nutritional Target-of-Rapamycin (TOR) pathway mediates blood-meal activation of mosquito reproductive cycles. Blood-derived amino acid (AA) signaling through the nutrient sensitive TOR kinase is critical for the transcriptional activation of the major yolk protein precursor (YPP) gene, vitellogenin (Vg), initiation of vitellogenesis and egg development. In this study, we provide in vitro and in vivo evidence that the Rheb GTPase (Ras Homologue Enriched in Brain), which is an upstream activator of TOR, is required for AA-mediated activation of the TOR pathway in the fat body of the mosquito Aedes aegypti. Using RNA interference (RNAi) methods, we showed that Rheb was indispensable in AA-induced phosphorylation of S6 kinase, a key downstream substrate of TOR activation. Rheb RNAi depletion resulted in significant downregulation of Vg transcription and translation in the mosquito fat body, which was monitored in vivo after blood meal or in vitro organ culture after AA stimulation. Egg development was severely hindered in mosquitoes with a Rheb RNAi depletion background. This study represents a notable step in deciphering molecular pathways controlling reproduction of this important vector of human diseases. PMID- 21035551 TI - Signal transducer and activator of transcription 3 (STAT3) homologue in turbot (Scophthalmus maximus): molecular characterization and expression analysis. AB - Signal transducer and activator of transcription 3 (STAT3) acts as an important mediator in multiple biological processes induced by different cytokines. So far, little information is available in fish STAT3. In this study, turbot (Scophthalmus maximus) STAT3 gene was cloned and characterized for the first time. The turbot STAT3 full-length cDNA consists of 2355 nucleotides encoding a polypeptide of 784 amino acids with four conserved domains including STAT_int, STAT_alpha, STAT_bind and SH2 domain. The phylogenetic tree showed that turbot STAT3 shared the closest relationship with mandarin fish (Siniperca chuatsi) STAT3. The autoactivation experiment in yeast proved that turbot STAT3 was a strong transcription factor. The quantitative RT-PCR experiment indicated that Stat3 mRNA was expressed in widespread tissues with the highest expression levels in the liver. And the further expression patterns analysis revealed that turbot Stat3 expression levels were increased in liver, spleen, kidney of fish infected with Vibrio anguillarum and liver of fish infected with LCDV. Meantime, hepcidin, one of STAT3 target gene, was also up-regulated in liver of fish infected with two pathogens. These results suggested that turbot Stat3 may involved in the immune defense process as a transcription factor. PMID- 21035552 TI - Thickness of the human cerebral cortex is associated with metrics of cerebrovascular health in a normative sample of community dwelling older adults. AB - We examined how wide ranges in levels of risk factors for cerebrovascular disease are associated with thickness of the human cerebral cortex in 115 individuals ages 43-83 with no cerebrovascular or neurologic history. Cerebrovascular risk factors included blood pressure, cholesterol, body mass index, creatinine, and diabetes-related factors. Variables were submitted into a principal components analysis that confirmed four orthogonal factors (blood pressure, cholesterol, cholesterol/metabolic and glucose). T1-weighted MRI was used to create models of the cortex for calculation of regional cortical thickness. Increasing blood pressure factor scores were associated with numerous regions of reduced thickness. Increasing glucose scores were modestly associated with areas of regionally decreased thickness. Increasing cholesterol scores, in contrast, were associated with thicker cortex across the whole brain. All findings were primarily independent of age. These results provide evidence that normal and moderately abnormal levels of parameters used to assess cerebrovascular health may impact brain structure, even in the absence of cerebrovascular disease. Our data have important implications for the clinical management of vascular health, as well as for what is currently conceptualized as "normal aging" as they suggest that subclinical levels of risk may impact cortical gray matter before a disease process is evident. PMID- 21035553 TI - Prediction of subsequent recognition performance using brain activity in the medial temporal lobe. AB - Application of multivoxel pattern analysis (MVPA) to functional magnetic resonance imaging (fMRI) data enables reconstruction and classification of cognitive status from brain activity. However, previous studies using MVPA have extracted information about cognitive status that is experienced simultaneously with fMRI scanning, but not one that will be observed after the scanning. In this study, by focusing on activity in the medial temporal lobe (MTL), we demonstrate that MVPA on fMRI data is capable of predicting subsequent recognition performance. In this experiment, six runs of fMRI signals were acquired during encoding of phonogram stimuli. In the analysis, using data acquired in runs 1-3, we first conducted MVPA-based voxel-wise search for the clusters in the MTL whose signals contained the most information about subsequent recognition performance. Next, using the fMRI signals acquired in runs 1-3 from the selected clusters, we trained a classifier function in MVPA. Finally, the trained classifier function was applied to fMRI signals acquired in runs 4-6. Consequently, we succeeded in predicting the subsequent recognition performance for stimuli studied in runs 4-6 with significant accuracy. This accurate prediction suggests that MVPA can extract information that is associated not only with concurrent cognitive status, but also with behavior in the near future. PMID- 21035554 TI - Volumetric MRI and MRS provide sensitive measures of Alzheimer's disease neuropathology in inducible Tau transgenic mice (rTg4510). AB - The purpose of this study was to determine if in vivo high resolution 3D MRI and localized (1)H MR spectroscopy (MRS) can detect brain findings resembling Alzheimer's disease in a transgenic mouse model of Tau pathology. Seven double transgenic rTg4510 female mice and 7 age-matched wild-type (wt) female mice were evaluated at 5 months of age. To confirm the usefulness and consistency of in vivo MRI/S, we also scanned the brains of 14 male mice (7 rTg4510 and 7 age matched wt) at 8 months of age. Mean hippocampal and cerebral cortex volumes in the female rTg4510 mice were 26.7% and 20.6% smaller than that in the wt controls (p<0.0001), respectively. Mean hippocampal and cerebral cortex volumes in the male rTg4510 mice were 18.4% and 16.9% smaller than that in the wt controls (p<0.00005), respectively. The mean volumes of the cerebellum were not statistically different between the rTg4510 and the wt groups. MRS assessment revealed that the myo-inositol to total creatine ratios (mIns/tCr), a measure of gliosis, were significantly higher in the hippocampus of rTg4510 mice relative to wt mice (p=0.03 for the females; p=0.005 for the males). Immunohistochemistry and histology in the same animals verified previously published data showing elevation of hyperphosphorylated Tau, glial activation and cortical and hippocampal neuronal loss. This study demonstrates that in vivo MRI/S can be a non-invasive biomarker to assess brain atrophy and related biochemical changes in the rTg4510 mouse model. PMID- 21035555 TI - Molecular systematics of Stenodactylus (Gekkonidae), an Afro-Arabian gecko species complex. AB - We conducted a phylogenetic analysis of Stenodactylus geckos using mitochondrial and three nuclear genes in order to understand the divergence within this genus. Stenodactylus is a complex with deep divergences that date to at least the Miocene; these patterns are seen in several other complexes in this region, indicating important and shared biogeographic processes affecting several taxonomic groups. Divergence between disjunct populations from three species in the Arabian Peninsula may have arisen because of Pliocene and Pleistocene restructuring of sand dunes. As currently recognized, Stenodactylus is not a monophyletic genus with respect to Tropiocolotes. We resurrect the monotypic genus Pseudoceramodactylus to address this problem of monophyly. PMID- 21035556 TI - UTE-T2* mapping of human articular cartilage in vivo: a repeatability assessment. AB - INTRODUCTION: Ultrashort echo-time enhanced T2* (UTE-T2*) mapping of articular cartilage is a novel quantitative MRI technique with the potential to visualize deep cartilage characteristics better than standard T2 mapping. The feasibility and intersession repeatability of UTE-T2* mapping of cartilage in vivo has not previously been evaluated. METHODS: Eleven asymptomatic subjects underwent repeat UTE-T2* imaging on a whole-body 3T MRI scanner on three consecutive days. Full thickness, superficial and deep regions of interest (ROIs) were evaluated in the central weight-bearing zones of the medial femoral condyle (cMFC) and tibial plateau (cMTP). Intersession precision error across subjects was evaluated by the root-mean-square average coefficients of variation (RMSA-CV) and by the median of intra-subject standard deviations (SDs) of UTE-T2* values in each ROI. RESULTS: UTE-T2* values in vivo were found to be repeatable with relative (RMSA-CV) intersession precision errors of 8%, 6%, 16% for full-thickness, superficial and deep cMFC ROIs, corresponding to absolute errors (SD) of 1.2, 1.5, 1.5 ms, respectively. In cMTP tissue, UTE-T2* relative repeatability was 8%, 8%, 13%, corresponding to absolute repeatability of 1.0, 1.5, 2.1 ms (full-thickness, superficial, deep). UTE-T2* values were higher in superficial cartilage compared to deep in both cMFC (P?0.001) and cMTP (P=0.0004) regions. CONCLUSION: In vivo 3D UTE-T2* mapping at 3T is feasible and can be implemented using a standard clinical MRI scanner and knee coil. Intersession precision error of UTE-T2* values in full-thickness ROIs in the weight-bearing regions of asymptomatic subjects is under 1.2 ms or 8% (RMSA-CV). Significant zonal and regional variations of UTE-T2* were seen. PMID- 21035557 TI - Selenomethionine inhibits IL-1beta inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2) expression in primary human chondrocytes. AB - OBJECTIVE: Several lines of evidence show that selenium (Se) has potential protective effects in osteoarthritis (OA), however the exact mechanism is still unclear. As interleukin-1beta (IL-1beta) is one of the key proinflammatory cytokines contributing to the progression in OA, we investigated the effect of Se in neutralizing the inflammatory effects of IL-1beta on nitric oxide (NO) and prostaglandin E2 (PGE2) production, and the signaling pathways involved. METHODS: Isolated primary human chondrocytes were pretreated with selenomethionine (SeMet) (0.5 MUM SeMet) for 24 h then co-treated without or with IL-1beta (10 pg/ml or 50 pg/ml) for another 24 h followed by RNA isolation. Gene expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX2) was determined by quantitative Real Time-Polymerase Chain Reaction. Culture media concentrations of NO and PGE2 were determined by nitrite (NO2-) assay and immunoassay respectively. For analysis of cell signaling pathways, chondrocytes were pretreated with SeMet then stimulated with IL-1beta for 0-45 min. The activity of IL-1beta signaling pathways was determined by Western blot screening of phosphorylation states of signal transduction proteins. RESULTS: SeMet inhibited chondrocyte gene expression of IL-1beta induced iNOS (31-54%, P=0.031) and COX2 (50-65%, P=0.031) with corresponding reductions in both NO (19-47%, P=0.031) and PGE2 (24-32%, P=0.031) production. Pretreatment with SeMet attenuated IL-1beta induced activation of p38 MAPK (39%, P=0.039) but not the extracellular signal-regulated kinase pathways (ERK) 1/2, c-Jun N-terminal kinases (JNK) or nuclear factor kappaB (NFkappaB). CONCLUSIONS: This study elucidates one potential protective mechanism of Se, namely through the alteration of cell signaling and downstream transcription of pro-inflammatory effects of IL-1beta. PMID- 21035558 TI - Nutraceuticals: do they represent a new era in the management of osteoarthritis? a narrative review from the lessons taken with five products. AB - OBJECTIVES: The aim of this first global systematic review on selected nutraceuticals was to synthesize and evaluate scientific relevant data available in the literature. Evidences that can support health, physiological or functional benefit on osteoarthritis (OA) were gathered and the level of evidence relative to each of these ingredients was highlighted. METHODOLOGY: Relevant scientific data (positive or not) regarding OA were searched for five groups of compounds (avocado/soybean unsaponifiables (ASU), n-3 polyunsaturated fatty acids, collagen hydrosylates (CHs), vitamin D, polyphenols) within preclinical (in vitro and in vivo), epidemiological, and clinical studies. The following criteria were evaluated to assess the methodology quality of each study: (1) study question; (2) study population; (3) primary endpoint; (4) study design (randomization, control, blinding, duration of follow up); (5) data analysis and interpretation. A scientific consensus was determined for all studied nutraceuticals to evaluate their efficacy in OA. RESULTS: The studied compounds demonstrated different potencies in preclinical studies. Most of them have demonstrated anti-catabolic and anti-inflammatory effects by various inhibitory activities on different mediators. Vitamin D showed a pro-catabolic effect in vitro and the polyphenol, Genistein, had only anti-inflammatory potency. The evaluation of the clinical data showed that ASU was the only one of the studied ingredients to present a good evidence of efficacy, but the efficient formulation was considered as a drug in some countries. Pycnogenol showed moderate evidence of efficacy, and vitamin D and collagen hydrolysate demonstrated a suggestive evidence of efficacy, whereas curcumin, epigallocatechin-3-gallate (EGCG) and resveratrol had only preclinical evidence of efficacy due to the lack of clinical data. The literature gathered for n-3 PUFA, nobiletin and genistein was insufficient to conclude for their efficacy in OA. CONCLUSION: Additional data are needed for most of the studied nutraceuticals. Studies of good quality are needed to draw solid conclusions regarding their efficacy but nutraceuticals could represent good alternates for OA management. Their use should be driven by any recommendations. PMID- 21035559 TI - Requirement of the NF-kappaB pathway for induction of Wnt-5A by interleukin-1beta in condylar chondrocytes of the temporomandibular joint: functional crosstalk between the Wnt-5A and NF-kappaB signaling pathways. AB - OBJECTIVE: We have previously reported that interleukin-1beta (IL-1beta) up regulates the expression of Wnt-5A and the activation of Wnt-5A signaling induces matrix metalloproteinase (MMP) through the c-Jun N-terminal kinase pathway in condylar chondrocytes (CCs) of the temporomandibular joint (TMJ). These results suggest that Wnt-5A could play an essential role in IL-1beta-mediated cartilage destruction. The objective of this study was to investigate the molecular mechanism underlying IL-1beta-induced up-regulation of Wnt-5A in TMJ CCs. METHODS: Primary CCs, limb chondrocytes (LCs) and SW1353 human chondrosarcoma cells were treated with IL-1beta in the presence or absent of BAY 11-7082 (an inhibitor of IkappaBalpha-phosphorylation). Then, expression of Wnt-5A was estimated by real-time reverse transcriptase-polymerase chain reaction (RT-PCR), Western blotting and immunocytofluorescence. Transient transfection of p65 expression vector and chromatin immunoprecipitation (ChIP) assay was performed to define the effect of p65 on Wnt-5A expression. RESULTS: IL-1beta up-regulated Wnt 5A expression at both the RNA and protein levels in articular chondrocytes. The inhibitor of IkappaBalpha-phosphorylation, BAY 11-7082, blocked the induction of Wnt-5A by IL-1beta in a dose-dependent manner. Moreover, experiments with overexpression of p65 and ChIP established that induction of Wnt-5A by IL-1beta is mediated through the NF-kappaB pathway, especially the p65 subunit. CONCLUSION: These results clarify the molecular mechanism underlying up regulation of Wnt-5A by IL-1beta in chondrocytes, suggesting an important functional crosstalk between Wnt-5A and NF-kappaB signaling pathways. This finding provides new insights into the involvement of Wnt signaling in the cartilage destruction caused by arthritis. PMID- 21035560 TI - The duration of bronchodilation of salmeterol and salbutamol as measured by specific airway conductance in healthy subjects. AB - According to the duration of bronchodilation, beta-2-agonists are divided into short and long acting bronchodilators. The bronchodilatory effect of available long acting beta-2-agonists (LABAs) beyond 12 h is not sufficiently studied. In order to evaluate the bronchodilatory effects of LABA in subjects without airway obstruction, the measurement of specific airway conductance (sGaw) with whole body plethysmography has been demonstrated to be a sensitive method. We aimed to determine the bronchodilatory effects of single doses of salmeterol 25, 50 and 200 MUg and salbutamol 200 MUg in healthy subjects (n = 16) over a 24 h period in a randomized, double-blind, triple-dummy, placebo-controlled cross-over-study. At the 12-h endpoint, all three doses of salmeterol significantly increased sGaw compared with placebo. At the 24-h endpoint, there was a significant increase in sGaw with salmeterol 200 MUg, while with 25 and 50 MUg salmeterol the sGaw increase failed to reach statistical significance. There was no statistically significant increase in sGaw with salbutamol 200 MUg at either the 12-h or 24-h endpoints. For weighted means, all three salmeterol doses showed statistically significant increase in sGaw compared with placebo over 0-12, 12-24 and 0-24 h periods, while for salbutamol 200 MUg a significant increase in sGaw was recorded only over 0-12 h period. We conclude that sGaw measurement is a suitable method for recording the bronchodilatory effect of beta-2-agonists in healthy subjects. Using this method we could demonstrate that salmeterol 200 MUg provides significant increase in specific airway conductance up to 24 h after a single dose. PMID- 21035561 TI - Down-regulation of activity and expression of three transport-related proteins in the gills of the euryhaline green crab, Carcinus maenas, in response to high salinity acclimation. AB - The euryhaline green crab, Carcinus maenas, undergoes an annual cycle of salinity exposure, having to adapt to low salinity during its annual spring migration into estuaries, and then having to re-adapt to high salinity when it moves off-shore at the end of summer. Most studies have focused on low salinity acclimation, the activation of osmoregulatory mechanisms, and the induction of transport protein and transport-related enzyme activity and gene expression. In this study we followed the changes in hemolymph osmolality, carbonic anhydrase activity, and mRNA expression of three proteins through a complete cycle of low (15 ppt) and high (32 ppt) salinity acclimation. One week of low salinity acclimation resulted in hemolymph osmoregulation and a four-fold induction of branchial carbonic anhydrase activity. Relative mRNA expression increased for two CA isoforms (CAc 100-fold, and CAg 7-fold) and the alpha-subunit of the Na/K-ATPase (8-fold). Upon re-exposure to high salinity, hemolymph osmolality increased to 32 ppt acclimated levels by 6 h, and mRNA levels returned to high salinity, baseline levels within 1 week. However, CA activity remained unchanged in response to high salinity exposure for the first week and then gradually declined to baseline levels over 4 weeks. The relative timing of these changes suggests that while whole-organism physiological adaptations and regulation at the gene level can be very rapid, changes at the level of protein expression and turnover are much slower. It is possible that the high metabolic cost of protein synthesis and/or processing could be the underlying reason for long biological life spans of physiologically important proteins. PMID- 21035562 TI - SARS coronavirus 8b reduces viral replication by down-regulating E via an ubiquitin-independent proteasome pathway. AB - The severe acute respiratory syndrome coronavirus (SARS-CoV) 8b protein, which is not expressed by other known coronaviruses, can down-regulate the envelope (E) protein via a proteasome-dependent pathway. Here, we showed that the down regulation of E is not dependent on the lysine residues on 8b and the reduction of polyubiquitination of E mutants is not correlated with their down-regulation by 8b, suggesting an ubiquitin-independent proteasome pathway is involved. A time course study revealed that 8b was expressed at late-stages of SARS-CoV infection. By using Vero E6 cells stably expressing green fluorescence protein-tagged 8b, ectopic expression of 8b was shown to significantly reduce the production of progeny virus and down-regulate E expression. Taken together, these results suggest that 8b negatively modulates virus replication by down-regulating E via an ubiquitin-independent proteasome pathway. PMID- 21035563 TI - Bone marrow-derived cells: A potential approach for the treatment of xerostomia. AB - Transplantations of bone marrow-derived cells (BMDCs) are traditionally used for hematologic diseases, but there are increasing numbers of clinical trials using BMDC treatments for non-hematologic disorders, including autoimmune diseases. BMDCs are recently reported to improve organ functions. This paper will review available reports supporting the role of BMDCs in reducing xerostomia (i.e. re establishing salivary gland functions) due to head and neck irradiation for cancer therapies and in Sjogren's syndrome. There are reports that BMDCs provide a beneficial effect on the saliva production. BMDCs positively affect blood vessels stability and regeneration in irradiated salivary glands. Also, BMDCs provide an immunomodulatory activity in mice with Sjogren's-like disease. While the exact mechanisms by which BMDCs improve organ functions remain controversial, there is preliminary evidence that a combination of them (such as cell transdifferentiation, vasculogenesis, and paracrine effect) occur in salivary glands. PMID- 21035564 TI - Tributyltin is a potent inhibitor of piscine peroxisome proliferator-activated receptor alpha and beta. AB - Increasing evidence suggests that common environmental contaminants can act as endocrine disrupters in fish. However, current data are biased towards environmental estrogens, highlighting the need to elucidate potential pollutant impact on other endocrine axes. Here, we report a high-throughput assay to identify chemicals interacting with piscine peroxisome proliferator-activated receptors (PPARs). Our transactivation assay employs a fish cell line and uses recombinant proteins combining the yeast Gal4 DNA-binding domain with the ligand binding domain of PPARs from plaice (Pleuronectes platessa). Compared to assays with full-length PPARs, this approach circumvents interaction of chemicals binding to retinoid X receptors, which form heterodimers with PPAR and many other nuclear receptors. Plaice PPARalpha and PPARbeta are activated by fibrate drugs and by phthalate mono-esters at concentrations similar to those activating the homologous mammalian receptors. In line with their assumed role as central transcriptional regulators of energy homeostasis, a number of fatty acids activate plaice PPARalpha and PPARbeta. In contrast, tributyl tin oxide (TBTO) is a potent antagonist of PPARalpha and PPARbeta, showing activity at environmentally relevant concentrations of TBTO (1-50 nM). Given the ubiquitous and persistent nature of TBTO, the possibility that chronic environmental effects are occurring via disruption of PPAR signalling in fish should be further investigated. PMID- 21035565 TI - Recruitment issues in a randomized controlled exercise trial targeting wheelchair users. AB - This paper describes recruitment challenges and lessons learned in conducting a randomized controlled exercise trial in the absence of direct access to a clinical population. One-hundred thirty-five wheelchair users were enrolled in a home and community-based intervention to promote exercise adoption and maintenance. Over 44 months of recruitment, 355 individuals inquired about the study and 323 completed the screening process. Nearly half were determined ineligible (150/323, 46.4%), typically due to having restricted arm movement, cognitive impairment, or medical conditions that are contraindicated for unsupervised exercise. Respondents cited paid media advertisements and recruitment materials placed in health care providers' offices most frequently as being how they learned about the study. RCT participant recruitment, particularly in the absence of direct access to a clinical population, required far more time and resources than anticipated to achieve sufficient enrollment. Nurturing relations with key gatekeepers, creating a visible public profile, and maintaining ongoing recruitment activities were essential to success. PMID- 21035566 TI - Biased distribution of IS629 among strains in different lineages of enterohemorrhagic Escherichia coli serovar O157. AB - The distribution of insertion sequence (IS) 629 among strains of enterohemorrhagic Escherichia coli serovar O157 (O157) was investigated and compared with the strain lineages defined by lineage specific polymorphism assay 6 (LSPA-6) to demonstrate the effectiveness of IS629 analysis for population genetics analysis. Using pulsed-field gel electrophoresis and variable-number tandem repeat typing, 140 strains producing both VT1 and VT2 and 98 strains producing only VT2 were selected from a total of 592 strains isolated from patients and asymptomatic carriers in Chiba Prefecture, Japan, during 2003-2008. By LSPA-6 analysis, six strains had atypical amplicon sizes in their Z5935 loci and five strains had atypical amplicon sizes in their arp-iclR intergenic regions. Sequence analyses of PCR amplified DNAs showed that five of the six loci used for LSPA-6 analysis had tandem repeats and the allele changes were due to changes in the number of tandem repeats. Subculturing and long-term incubation was found to have no detectable effect on the lineages defined by LSPA-6 analysis, demonstrating the robustness of LSPA-6 analysis. Minimum spanning tree analysis reconstruction revealed that strains in lineage I, I/II, and II clustered on separate branches, indicating that the distribution of IS629 was biased among O157 strains in different lineages. Strains with LSPA-6 codes 231111, 211113, and 211114 had atypical amplicon sizes and were clustered in lineage I/II branch, and strains with LSPA-6 codes 212114, 221123, 221223, 222123, 222224, 242123, 252123, and 242222 had atypical amplicon sizes and clustered in lineage II branches. Linkage disequilibrium was observed in strains in every lineage when the standardized index of association was calculated using IS629 distribution data. Therefore, the distribution analysis of IS629 may be effective for population genetics analysis of O157 due to the biased IS629 distribution among strains in the three O157 lineages. PMID- 21035567 TI - Full genomic analysis of a simian SA11-like G3P[2] rotavirus strain isolated from an asymptomatic infant: identification of novel VP1, VP6 and NSP4 genotypes. AB - We report here the full genomic analysis of a simian SA11-like G3P[2] group A rotavirus (GAR) strain, B10, isolated from an asymptomatic infant in Kenya in 1987. By nucleotide sequence identities and phylogenetic analyses, the VP7-VP4 VP2-VP3-NSP1-NSP2-NSP3-NSP5 genes of strain B10 exhibited maximum genetic relatedness to those of the different isolates of simian strain SA11, and were assigned to the G3-P[2]-C5-M5-A5-N5-T5-H5 genotypes, respectively. On the other hand, the VP1, VP6 and NSP4 genes of strain B10 did not belong to any of the established GAR genotypes, and therefore, were assigned to new genotype numbers R8, I16 and E13, respectively, by the Rotavirus Classification Working Group. These observations suggested that strain B10 might have originated from reassortment event/s involving simian SA11-like strains and GAR strains from unknown animal host species (possibly other wild animals) preceding transmission to humans. Alternatively, considering the lack of data on simian GARs, it might be also possible that the VP1, VP6 and NSP4 genes of strain B10 are those of unknown simian strains, and that strain B10 might be a typical simian strain that was directly transmitted to humans. Therefore, either hypothesis pointed towards a rare instance of possible direct transmission of GARs from an animal host (possibly a monkey or some other wild animal) to humans. This was corroborated by the presence of different species of wild animals including non-human primates, and unhygienic conditions at the sampling site. To our knowledge, the present study is the first report on the detection of a simian SA11-like G3P[2] GAR strain in humans. PMID- 21035568 TI - Role of 5-HT1(A) receptors in induction and preservation of phrenic long-term facilitation in rats. AB - The aim was to investigate the role of 5-HT1(A) receptor activation in induction and preservation of phrenic long-term facilitation (pLTF) at two different time points, before exposures to episodic hypoxia and after pLTF was induced. Adult, male, urethane anesthetized, vagotomized, paralyzed, and mechanically ventilated Sprague-Dawley rats were exposed to an acute intermittent hypoxia (AIH) protocol. Experimental groups of animals received an intravenous injection of WAY-100635, before the onset of the first hypoxic stimulus (WAY0), and after pLTF was induced (WAY60). Peak phrenic nerve activity (pPNA), burst frequency (f), and respiratory rhythm parameters were analyzed during the five hypoxic exposures (TH1-5), as well as at 15 min (T15), 30 min (T30), and 60 min (T60) after the end of the last hypoxic episode. In the control group, pPNA was elevated from baseline (121.6 +/- 7.3%, P < 0.001) at 60 min after episodic hypoxia indicating pLTF. Administration of WAY-100635 prior to hypoxic stimulation prevented the induction of pLTF. Additionally, administration of WAY-100635 after pLTF developed impaired preservation of pLTF. In conclusion, there is an important role for 5-HT1(A) receptors in induction as well as in preservation of pLTF in urethane anesthetized rats. PMID- 21035569 TI - Characterization of low-energy excited states in the native state ensemble of non myristoylated and myristoylated neuronal calcium sensor-1. AB - Information on the low-energy excited states of a given protein is important as this controls the structural adaptability and various biological functions of proteins such as co-operativity, response towards various external perturbations. In this article, we characterized individual residues in both non-myristoylated (non-myr) and myristoylated (myr) neuronal calcium sensor-1 (NCS-1) that access alternate states by measuring nonlinear temperature dependence of the backbone amide-proton (1H(N)) chemical shifts. We found that ~20% of the residues in the protein access alternative conformations in non-myr case, which increases to ~28% for myr NCS-1. These residues are spread over the entire polypeptide stretch and include the edges of alpha-helices and beta-strands, flexible loop regions, and the Ca2(+)-binding loops. Besides, residues responsible for the absence of Ca2(+) myristoyl switch are also found accessing alternative states. The C-terminal domain is more populated with these residues compared to its N-terminal counterpart. Individual EF-hands in NCS-1 show significantly different number of alternate states. This observation prompts us to conclude that this may lead to differences in their individual conformational flexibility and has implications on the functionality. Theoretical simulations reveal that these low-energy excited states are within an energy band of 2-4 kcal/mol with respect to the native state. PMID- 21035570 TI - Exploring and exploiting allostery: Models, evolution, and drug targeting. AB - The concept of allostery was elaborated almost 50years ago by Monod and coworkers to provide a framework for interpreting experimental studies on the regulation of protein function. In essence, binding of a ligand at an allosteric site affects the function at a distant site exploiting protein flexibility and reshaping protein energy landscape. Both monomeric and oligomeric proteins can be allosteric. In the past decades, the behavior of allosteric systems has been analyzed in many investigations while general theoretical models and variations thereof have been steadily proposed to interpret the experimental data. Allostery has been established as a fundamental mechanism of regulation in all organisms, governing a variety of processes that range from metabolic control to receptor function and from ligand transport to cell motility. A number of studies have shed light on how evolutionary pressures have favored and molded the development of allosteric features in specific macromolecular systems. The widespread occurrence of allostery has been recently exploited for the development and design of allosteric drugs that bind to either physiological or non-physiological allosteric sites leading to gain of function or loss of function. This article is part of a Special Issue entitled: Protein Dynamics: Experimental and Computational Approaches. PMID- 21035571 TI - Surface plasmon resonance study on functional significance of clustered organization of lectin-like oxidized LDL receptor (LOX-1). AB - Lectin-like oxidized low-density lipoprotein (OxLDL) receptor 1 (LOX-1) is the major OxLDL receptor of vascular endothelial cells and is involved in an early step of atherogenesis. LOX-1 exists as a disulfide-linked homodimer on the cell surface, which contains a pair of the ligand-binding domains (CTLD; C-type lectin like domain). Recent research using living cells has suggested that the clustered state of LOX-1 dimer on the cell is functionally required. These results questioned how LOX-1 exists on the cell to achieve OxLDL binding. In this study, we revealed the functional significance of the clustered organization of the ligand-binding domain of LOX-1 with surface plasmon resonance. Biotinylated CTLD was immobilized on a streptavidin sensor chip to make CTLD clusters on the surface. In this state, the CTLD had high affinity for OxLDL with a dissociation constant (K(D)) in the nanomolar range. This value is comparable to the K(D) measured for LOX-1 on the cell. In contrast, a single homodimeric LOX-1 extracellular domain had lower affinity for OxLDL in the supra-micromolar range of K(D). Monomeric CTLD showed marginal binding to OxLDL. In combination with the analyses on the loss-of-binding mutant W150A, we concluded that the clustered organization of the properly formed homodimeric CTLD is essential for the strong binding of LOX-1 to OxLDL. PMID- 21035572 TI - Study of consanguineous populations can improve the annotation of SNP databases. AB - Our view of SNPs has evolved significantly from harmless mutational events that accumulated through the history of human race to important players in human health and disease. As a result, determining the pathologic vs. benign nature of SNPs on pure statistical basis is now viewed as too simplistic. Here, we show that two previously reported SNPs in COL6A2 and AGL represent disease-causing mutation for Ullrich Muscular Dystrophy and Glycogenosis type III, respectively, in homoallelic state. This report urges caution in interpreting SNPs in databases in the clinical genetics setting and calls for sequencing runs of homozygosity in healthy individuals as a promising approach to better annotate SNP databases. PMID- 21035573 TI - Drosophila vigilin, DDP1, localises to the cytoplasm and associates to the rough endoplasmic reticulum. AB - Functional characterisation of vigilin, a highly conserved multi-KH-domain protein that binds RNA and ssDNA, remains elusive and, to some extent, controversial. Studies performed in Saccharomyces cerevisiae and human cells indicate that vigilin localises to the cytoplasm, binds ribosomes, associates to RER and regulates mRNA translation. On the other hand, we and others reported a contribution to heterochromatin-mediated gene silencing (PEV) and chromosome segregation in S. cerevisiae, Drosophila and human cells. Whether this contribution is direct remains, however, unclear. Here, we report that Drosophila vigilin, DDP1, vastly localises to the cytoplasm, being largely excluded from the nucleus. We also show that DDP1 preferentially associates to RER and co-purifies with several ribosomal proteins, suggesting a contribution to mRNA translation. In light of these results, the contribution of DDP1 to PEV was re-examined. Here, we show that a newly generated null ddp1(Delta) mutation is only a weak suppressor of PEV, which is in contrast with our own previous results showing dominant suppression in the presence of a strong hypomorphic ddp1(15.1) mutation. Similar results were obtained in the fission yeast Schizosaccharomyces pombe, where vigilin (Vgl1) also associates to RER, having no significant contribution to PEV at centromeres, telomeres and the mating-type locus. Altogether, these results indicate that cytoplasmic localisation and association to RER, but not contribution to heterochromatin organisation, are evolutionarily conserved features of vigilin, favouring a model by which vigilin acts in the cytoplasm, regulating RNA metabolism, and affects nuclear functions only indirectly. PMID- 21035575 TI - Bone disease and skeletal complications in patients with beta thalassemia major. AB - Increased survival in patients with beta thalassemia major (TM) allowed for several complications of the disease and its treatment to manifest, one of which is bone disease. Osteoporosis in this patient population results from a variety of genetic and acquired factors. Early diagnosis and prevention are essential and several measures have been evaluated for management including bisphosphonates. Fracture prevalence in TM patients seems to be clustered in mid adulthood, and is related to vitamin D deficiency and low bone mineral density. Fracture healing in patients with TM does not seem to be different from that in normal individuals. Bone and joint pain are a common manifestation of the underlying pathophysiology or may be related to iron chelator intake. Intervertebral disc changes are seen in patients who are heavily iron overloaded or those who are chelated with deferoxamine. Spinal deformity is common in TM, yet the prognosis is benign with spontaneous resolution frequently observed. Further research is warranted to evaluate the mechanisms, clinical implications, and optimal management of bone disease in this patient population. PMID- 21035574 TI - The zinc-sensing transcription factor MTF-1 mediates zinc-induced epigenetic changes in chromatin of the mouse metallothionein-I promoter. AB - Metallothionein (MT) is a small, cysteine-rich protein active in zinc homeostasis, cadmium detoxification, and protection against reactive oxygen species. Mouse MT-I gene transcription is regulated by metal response element binding transcription factor-1 (MTF-1), which is recruited to the promoter by zinc. We examined alterations in the chromatin structure of the MT-I promoter associated with enhanced transcriptional activation. MTF-1 proved essential for zinc-induced epigenetic changes in the MT-I promoter. Chromatin immunoprecipitation assays demonstrated that zinc treatment rapidly decreased Lys4-trimethylated and Lys9-acetylated histone H3 in the promoter and decreased total histone H3 but not histone H3.3. Micrococcal nuclease sensitivity of the MT I promoter was increased by zinc. Thus, the chromatin structure in the promoter may be locally disrupted by zinc-induced nucleosome removal. Without MTF-1 these changes were not observed, and an MTF-1 deletion mutant recruited to the MT-I promoter by zinc that did not recruit the coactivator p300 or activate MT-I transcription did not affect histone H3 in the MT-I promoter in response to zinc. Interleukin-6, which induces MT-I transcription independently of MTF-1, did not reduce histone H3 levels in the promoter. Rapid disruption of nucleosome structure at the MT-I promoter is mediated by zinc-responsive recruitment of an active MTF-1-coactivator complex. PMID- 21035576 TI - Antibacterial activity of bone allografts: comparison of a new vancomycin tethered allograft with allograft loaded with adsorbed vancomycin. AB - Bacterial contamination of bone allograft is a significant complication of orthopedic surgery. To address this issue, we have engineered a method for covalently modifying bone allograft tissue with the antibiotic vancomycin. The goal of this investigation was to compare the biocidal properties of this new allograft material with those of vancomycin physisorbed onto graft material. The duration of antibiotic release from the vancomycin-modified allograft matrix was determined, and no elution was observed. In contrast, the adsorbed antibiotic showed a peak elution at 24h that then decreased over several days. We next used an Staphylococcus aureus disk diffusion assay to measure the activity of the eluted vancomycin. Again we found that no active antibiotic was eluted from the covalently modified allograft. Similarly, when the vancomycin-modified allograft morsel was used in the assay, no measurable elution was observed; amounts of antibiotic released from the adsorbed samples inhibited S. aureus growth for 4-7 days. Probably the most telling property of the allograft was that after 2 weeks, the tethered allograft was able to resist bacterial colonization. Unlike the elution system in which vancomycin was depleted over the course of days-weeks, the antibiotic on the allograft was stably bound even after 300 days, while its biocidal activity remained undiminished for 60 days. This finding was in stark contrast to the antibiotic impregnated allograft, which was readily colonized by bacteria. Finally we chose to evaluate three indicators of cell function: expression of a key transcription factor, expression of selected transcripts, and assessment of cell morphology. Since the tethered antibiotic appeared to have little or no effect on any of these activities, it was concluded that the stable, tethered antibiotic prevented bacterial infection while not modifying bone cell function. PMID- 21035577 TI - High dietary intake of retinol leads to bone marrow hypoxia and diaphyseal endosteal mineralization in rats. AB - Vitamin A (retinol) is the only molecule known to induce spontaneous fractures in laboratory animals and we have identified retinol as a risk factor for fracture in humans. Since subsequent observational studies in humans and old animal data both show that high retinol intake appears to only have small effects on bone mineral density (BMD) we undertook a mechanistic study of how excess retinol reduces bone diameter while leaving BMD essentially unaffected. We fed growing rats high doses of retinol for only 1 week. Bone analysis involved antibody-based methods, histology, pQCT, biomechanics and bone compartment-specific PCR together with Fourier Transform Infrared Spectroscopy of bone mineral. Excess dietary retinol induced weakening of bones with little apparent effect on BMD. Periosteal osteoclasts increased but unexpectedly endosteal osteoclasts disappeared and there was a reduction of osteoclastic serum markers. There was also a lack of capillary erythrocytes, endothelial cells and serum retinol transport protein in the endosteal/marrow compartment. A further indication of reduced endosteal/marrow blood flow was the increased expression of hypoxia-associated genes. Also, in contrast to the inhibitory effects in vitro, the marrow of retinol-treated rats showed increased expression of osteogenic genes. Finally, we show that hypervitaminotic bones have a higher degree of mineralization, which is in line with biomechanical data of preserved stiffness in spite of thinner bones. Together these novel findings suggest that a rapid primary effect of excess retinol on bone tissue is the impairment of endosteal/marrow blood flow leading to hypoxia and pathological endosteal mineralization. PMID- 21035578 TI - The foundation role of beta blockers across the cardiovascular disease spectrum: a year 2009 update. AB - Hypertension is a risk factor for myocardial infarction (MI), stroke, and heart failure and precedes heart failure in 91% of cases. This becomes even more important considering that the number of Americans with hypertension increased from 65 million in 2005 to 72 million in 2007. If blood pressure is effectively controlled this risk can be minimized-blood pressure reductions as small as 2 mm Hg have been shown to reduce the risk of cardiovascular events by up to 10%. There is also strong evidence that blood pressure targets for populations at high risk of cardiovascular disease, including those with diabetes, coronary artery disease, and chronic kidney disease, should be lower than 140/90 mm Hg. The number and type of antihypertensive drugs have increased dramatically from 28 diuretics in 1972 to over 125 agents today, including fixed dose combination dosage forms. Beta blockers have been available for the treatment of hypertension since the 1960s. However, there has been resistance to using these agents in patients with diabetes and renal failure because of metabolic side effects, and in other patients because of tolerability concerns such as depression, weight gain, and impotence. Two newer beta blockers with vasodilatory effects (carvedilol and nebivolol) have proven efficacy and tolerability in patients with hypertension and appear to lack the adverse effects associated with older beta blockers. Carvedilol causes vasodilation by alpha blockade, and nebivolol via nitric oxide mechanisms. Both of these agents reduce peripheral vascular resistance and maintain cardiac output. Clinical trial evidence to date leads to the conclusion that beta blockers are strongly indicated post-MI and in all patients with left ventricular dysfunction regardless of symptoms. Their beneficial abilities include improvement of oxygen supply and demand (which can reduce myocardial ischemia), anti-arrhythmic properties, and beneficial effects on cardiac remodeling. PMID- 21035580 TI - Measuring duty hours made simple. PMID- 21035582 TI - Livedo reticularis and erythematous macules of the forearms indicating cutaneous microscopic polyangiitis. PMID- 21035583 TI - Are we missing ways to reduce health care costs? PMID- 21035584 TI - Managing myocardial infarction in the elderly: what should the clinician do? PMID- 21035585 TI - Realistic assessment of drug-induced adverse events: a double-edged sword. PMID- 21035586 TI - Sporting events affect spectators' cardiovascular mortality: it is not just a game. AB - Physiologic and clinical triggers, including mental stress, anxiety, and anger, often precipitate acute myocardial infarction and cardiovascular death. Sporting events can acutely increase cardiovascular event and death rates. A greater impact is observed in patients with known coronary artery disease and when stressful features are present, including a passionate fan, a high-stakes game, a high-intensity game, a loss, and a loss played at home. Sporting events affect cardiovascular health through neuroendocrine responses and possibly an increase in high-risk behaviors. Acute mental stress increases the activity of the hypothalamic-pituitary-adrenocortical axis and the sympathetic-adrenal-medullary system while impairing vagal tone and endothelial function. Collectively, these mechanisms increase myocardial oxygen demand and decrease myocardial oxygen supply while also increasing the risk of arrhythmias and thrombosis. Measures can be taken to reduce cardiovascular risk, including the use of beta-blockers and aspirin, stress management, transcendental meditation, and avoidance of high-risk activities, such as smoking, eating fatty foods, overeating, and abusing alcohol and illicit drugs. Sporting events have the potential to adversely affect spectators' cardiovascular health, and protective measures should be considered. PMID- 21035587 TI - Clinical relevance of hibernating myocardium in ischemic left ventricular dysfunction. AB - Patients with chronic ischemic left ventricular dysfunction may have a substantial amount of viable, hibernating myocardium, which is a state of chronic contractile dysfunction with reduced blood flow at rest. Coronary revascularization in these patients may result in improvement of left ventricular function; in the absence of viability, left ventricular function will not improve postrevascularization. Various noninvasive imaging techniques are available for detection of viable myocardium, including magnetic resonance imaging, dobutamine stress echocardiography, and nuclear imaging with single photon emission computed tomography or positron emission tomography. Because these techniques probe different characteristics of viable myocardium, the sensitivities and specificities of the techniques are not precisely identical; in general, dobutamine stress echocardiography has the highest specificity, whereas the nuclear techniques have the highest sensitivity. The presence of myocardial viability also is related to prognosis: patients with viable myocardium who undergo revascularization have a good prognosis, whereas patients with viable myocardium who are treated medically have poor outcome. Accordingly, assessment of viability is important in the therapeutic decision-making process of patients with chronic ischemic left ventricular dysfunction. PMID- 21035588 TI - Muehrcke's lines. PMID- 21035589 TI - An unexpected source. PMID- 21035590 TI - Declining length of stay for patients hospitalized with AMI: impact on mortality and readmissions. AB - BACKGROUND: Length of hospital stay after acute myocardial infarction decreased significantly in the 1980s and 1990s. Whether length of stay has continued to decrease during the 2000s, and the impact of decreasing length of stay on rehospitalization and mortality, is unclear. We describe decade-long (1995-2005) trends in length of stay after acute myocardial infarction, and examine whether declining length of stay has impacted early rehospitalization and postdischarge mortality in a population-based sample of hospitalized patients. METHODS: The study sample consisted of 4184 patients hospitalized with acute myocardial infarction in a central New England metropolitan area during 6 annual periods (1995, 1997, 1999, 2001, 2003, 2005). RESULTS: The average age of the study sample was 71 years, and 54% were men. The average length of stay decreased by nearly one third over the 10-year study period, from 7.2 days in 1995 to 5.0 days in 2005 (P <.001). Younger patients (<65 years), men, and patients with an uncomplicated hospital stay had significantly shorter lengths of stay than respective comparison groups. Lengths of stay shorter than the median were not associated with significantly higher odds of hospital readmission at 7 or 30 days postdischarge, or with mortality in the year after discharge. In contrast, longer lengths of stay were associated with significantly higher odds of short-term mortality. These findings did not vary by year under study. CONCLUSIONS: Length of stay in patients hospitalized for acute myocardial infarction decreased significantly between 1995 and 2005. Declining length of stay is not associated with an increased risk for early readmission or all-cause mortality. PMID- 21035591 TI - Angiotensin-converting enzyme inhibitor associated cough: deceptive information from the Physicians' Desk Reference. AB - BACKGROUND: Dry cough is a common, annoying adverse effect of all angiotensin converting enzyme (ACE) inhibitors. The present study was designed to compare the rate of coughs reported in the literature with reported rates in the Physicians' Desk Reference (PDR)/drug label. METHODS: We searched MEDLINE/EMBASE/CENTRAL for articles published from 1990 to the present about randomized clinical trials (RCTs) of ACE inhibitors with a sample size of at least 100 patients in the ACE inhibitors arm with follow-up for at least 3 months and reporting the incidence or withdrawal rates due to cough. Baseline characteristics, cohort enrolled, metrics used to assess cough, incidence, and withdrawal rates due to cough were abstracted. RESULTS: One hundred twenty-five studies that satisfied our inclusion criteria enrolled 198,130 patients. The pooled weighted incidence of cough for enalapril was 11.48% (95% confidence interval [CI], 9.54% to 13.41%), which was ninefold greater compared to the reported rate in the PDR/drug label (1.3%). The pooled weighted withdrawal rate due to cough for enalapril was 2.57% (95% CI, 2.40-2.74), which was 31-fold greater compared to the reported rate in the PDR/drug label (0.1%). The incidence of cough has increased progressively over the last 2 decades with accumulating data, but it has been reported consistently several-fold less in the PDR compared to the RCTs. The results were similar for most other ACE inhibitors. CONCLUSION: The incidence of ACE inhibitor-associated cough and the withdrawal rate (the more objective metric) due to cough is significantly greater in the literature than reported in the PDR/drug label and is likely to be even greater in the real world when compared with the data from RCTs. There exists a gap between the data available from the literature and that which is presented to the consumers (prescribing physicians and patients). PMID- 21035592 TI - Pulmonary hypertension and long-term mortality in aortic and mitral regurgitation. AB - BACKGROUND: Outcomes data in patients with aortic regurgitation or mitral regurgitation have been limited to small series with generally <10 years of follow-up. The quantitative impact of pulmonary artery hypertension has not been well described. The purpose of this study was to describe the 15-year mortality of aortic regurgitation and mitral regurgitation. METHODS: Our institution's electronic echocardiography database was queried to identify those patients examined in 1992 and reported to have at least mild aortic regurgitation or mitral regurgitation. Patients were classified by semi-quantitative degree of regurgitation. Pulmonary artery systolic pressure was categorized as normal, borderline, mild, or moderate or greater hypertension (pulmonary artery systolic pressure >40 mm Hg). Age-stratified Cox proportional hazards models compared survival among groups and adjusted for sex, depressed left ventricular ejection fraction, and pulmonary artery systolic pressure. Mortality data were obtained from the 2008 Social Security Death Index. RESULTS: Of 4984 echocardiograms performed in 4050 patients, 1156 patients (28%; aged 72+/-14 years) had at least mild aortic regurgitation and 1971 patients (49%; aged 69+/-16 years) had at least mild mitral regurgitation. Overall 15-year mortality in patients with aortic regurgitation was 74% and similar for all grades of aortic regurgitation. Overall 15-year mortality in patients with mitral regurgitation was 71% and got progressively worse with increasing severity grade of mitral regurgitation (63% for mild to 81% for at least moderate-to-severe). For both aortic and mitral regurgitation, moderate or greater pulmonary artery systolic hypertension was associated with increased mortality (in patients with aortic regurgitation, hazard ratio [HR], 1.94; 95% confidence interval [CI], 1.58-2.41, and in mitral regurgitation patients, HR, 1.48; 95% CI, 1.26-1.75). CONCLUSION: Long-term (15 year) survival of patients with aortic regurgitation is poor and is independent of regurgitation severity. In contrast, long-term survival of patients with mitral regurgitation correlates with regurgitation severity. For both groups, moderate or greater pulmonary artery systolic hypertension identified those at highest risk. PMID- 21035593 TI - Significance of elevated cardiac troponin T levels in critically ill patients with acute respiratory disease. AB - BACKGROUND: Elevations in cardiac troponin have prognostic importance in critically ill patients. However, there are no data addressing the independent association between troponin levels and mortality, adjusted for the severity of the underlying disease, in patients hospitalized for acute respiratory disorders. We investigated whether troponin T (cTnT) elevations are independently associated with in-hospital mortality in patients in the intensive care unit (ICU) admitted for severe and acute respiratory conditions. After adjusting for the severity of disease measured by the Acute Physiology, Age, and Chronic Health Evaluation (APACHE) III prognostic system, we evaluated short-term (30 days) and long-term (3 years) mortality. METHODS: We studied the APACHE III database and cTnT levels from patients admitted consecutively to the ICU at Mayo Clinic, Rochester, Minnesota. Between January 2001 and December 2005, 2078 patients with respiratory conditions had cTnT measured at ICU admission. In-hospital, short-term (30 days) and long-term (3 years) all-cause mortality were determined. RESULTS: Of the study patients, 878 (42.3%) had elevated cTnT and 1200 patients (57.7%) had undetectable cTnT. During hospitalization, 1.1% of the patients with troponin T <0.01 ng/mL died compared to 21% of those with troponin T >=0.01 ng/mL (P <.0001). At 30 days, mortality was 18.6% in patients with elevations of cTnT and 1.5% in patients without elevations of cTnT (P <.0001). The Kaplan-Meier probability of survival at 1-year follow-up was 71.0%, at 2-year follow-up was 48.3%, and 3-year follow-up was 39.4% with troponin T >=0.01 ng/mL and at 1-year follow-up was 98.8%, at 2-year follow-up was 97.2%, and at 3-year follow-up was 95.5% with troponin T <0.01 MUg/L (P <.0001). After adjustment for severity of disease and baseline characteristics, cTnT levels remained associated with in hospital, short-term and long-term mortality (P <.0001). CONCLUSIONS: In patients admitted to the ICU for respiratory disorders, cTnT elevations are independently associated with in-hospital, short-term and long-term mortality. PMID- 21035594 TI - Risk of intraoperative hypotension with loop diuretics: a randomized controlled trial. AB - BACKGROUND: There is growing concern regarding the safety of blood pressure lowering medications administered during the perioperative period. Whether loop diuretics also induce intraoperative hypotension is uncertain. Our objective was to compare the effects of continuing or withholding furosemide on the day of noncardiac elective surgery on intraoperative hypotension among chronic users of furosemide. METHODS: A double blind, randomized, placebo controlled trial was conducted at 3 North American university centers between September 2000 and December 2006. Participants were randomly assigned in a 1:1 ratio to receive either furosemide or placebo on the day of surgery. The primary outcome was risk of developing intraoperative hypotension. A priori secondary outcomes included risk of heart failure; composite cardiovascular event (myocardial infarction, arrhythmia, stroke or transient ischemic attack, or death); and change in renal function and electrolytes. RESULTS: Of the 212 patients enrolled, 193 patients underwent surgery. There was no significant difference in risk of developing intraoperative hypotension between the furosemide (49%) and placebo (51.9%) groups (relative risk [RR], 0.95; 95% confidence interval [CI], 0.72-1.24; P = .78). The intraoperative administration of vasopressors and fluids were similar between both groups. The risk of developing postoperative cardiovascular events was not significantly different between those randomized to furosemide (4.8%) or placebo (2.8%) (RR, 1.73; 95% CI, 0.42-7.06; P = .49). There was no significant difference in renal function or electrolytes between the 2 groups. CONCLUSION: Among elective, noncardiac surgeries in patients chronically treated with furosemide, the administration of furosemide on the day of surgery did not significantly increase the risk for intraoperative hypotension. PMID- 21035595 TI - AAIM report on master teachers and clinician educators part 4: faculty role and scholarship. PMID- 21035596 TI - Polyion-sensitive membrane-based electrodes for heparin-binding foldamer analysis. AB - Polymer membrane-based electrodes sensitive to low molecular weight heparin (LMWH) have been used to examine the binding between several preparations of LMWH and heparin-binding foldamers, which have recently been developed as potential inhibitors of the anticoagulant activity of LMWHs. It was found that the structure of the heparin-binding foldamer affects the equilibrium binding constant, K(eq), determined by analysis of the titration curves of the foldamers with LMWHs monitored with these electrodes, and further, the strength of binding depends on the specific LMWH preparation. Additionally, polymer membrane-based electrodes utilizing dinonylnaphthalene sulfonate as the ion-exchanger were developed to measure the heparin-binding foldamers directly in whole blood, and the response was found to depend on the lipophilicity and charge density of the foldamer. PMID- 21035597 TI - A review on viral biosensors to detect human pathogens. AB - Rapid identification of viruses has important implications for medical healthcare. Current methods for identification and quantification of particular virus are time consuming and often expensive. Therefore, demand for sensitive and accurate viral biosensors with rapid detection systems is increasing. A hand held biosensing device would give fast, reliable results for identifying and quantitating the number of virus particles in a sample. Techniques currently being applied to achieve this aim include electrochemical biosensors, based on amperometric, potentiometric and impedance measurement, optical biosensors using surface plasmon resonance (SPR), optical fibers and piezoelectric biosensors based on microcantilevers. Future research also looks to the use of nanoparticles and novel nanomaterials as alternate recognition surfaces for use in a variety of sensor formats. PMID- 21035598 TI - Layer-by-layer assembled molecularly imprinted polymer modified silver electrode for enantioselective detection of D- and L-thyroxine. AB - The present work describes a new, simple, and easy method for the generation of stable molecularly imprinted sites in polymeric film, combining self-assembled monolayer and Layer-by-layer approaches through thermal cross-linking of the layered structures, onto the surface of silver electrode. Modified silver electrodes demonstrate enantiodifferentiation and sensitive (detection limits 0.0060 ng mL(-1) for L- and 0.0062 for D-thyroxine) determination of d- and l thyroxine with the help of differential pulse anodic stripping voltammetric technique. The binding kinetics of thyroxine was explored using anodic stripping cyclic voltammetry and chronocoulometry. The sensor was also validated for D- and L-thyroxine determinations in biological and pharmaceutical samples. PMID- 21035599 TI - A novel ion selective sensor for promethium determination. AB - This is a first promethium(145) ion-selective sensor based on the comparative study of two Schiff base ligands (X(1) and X(2)) as neutral ionophores. Effect of various plasticizers: 2-nitrophenyloctylether (o-NPOE), dibutyl phosphonate (DBP), dioctylphthalate (DOP), tri-(2-ethylhexyl) phosphate (TEHP), dibutyl butylphosphonate (DBBP), chloronaphthalene (CN) and anion excluders: potassium tetrakis (p-chloropheny1) borate (KTpClPB), sodiumtetraphenylborate (NaTPB) and oleic acid (OA) have been studied. The membrane with a composition of ionophore (X(1)/X(2)):KTpClPB:PVC:o-NPOE (w/w, %) in the ratio of 5:5:30:60 exhibited best performance. The best responsive membrane sensors (8 and 21) exhibited working concentration range of 4.5*10(-7)-1.0*10(-2) M and 3.5*10(-6)-1.0*10(-2) M with a detection limits of 3.2*10(-7) M and 2.3*10(-6) M and Nernstian slopes of 20.0+/ 0.5, 19.5+/-0.5 mV decade(-1) of activity, respectively. The sensor no. 8 works satisfactorily in partially non-aqueous media up to 10% (v/v) content of methanol, ethanol and acetonitrile. Analytical application of the proposed sensor has been demonstrated in determination of promethium (III) ions in spiked water samples. PMID- 21035600 TI - A new approach for simultaneous screening and quantification of toxic pyrrolizidine alkaloids in some potential pyrrolizidine alkaloid-containing plants by using ultra performance liquid chromatography-tandem quadrupole mass spectrometry. AB - A rapid, but sensitive and selective method for simultaneous screening and quantification of toxic pyrrolizidine alkaloids (PAs) by ultra performance liquid chromatography (UPLC) coupled with tandem mass spectrometry (MS/MS) on a tandem quadrupole mass spectrometer (TQ-MS) is described. This was accomplished by incorporating the precursor ion scan (PIS) acquisition and multiple reaction monitoring (MRM) acquisition in the same UPLC-MS/MS run. Notably, the developed PIS approach for detecting two pairs of characteristic product ions at m/z 120/138 or 168/150, allowed specific identification of toxic retronecine and otonecine types PAs. This PIS method is highly sensitive with over 10-fold sensitivity improvement upon previously published LC-MS method. Moreover, this new approach is suitable for high sample throughput and was applied to the screening and quantifying toxic PAs in 22 samples collected from seven Parasenecio species and four Senecio species. In addition, coupling the MRM with PIS approach generated quantitative results equivalent to those obtained by conventional MRM-only approach. This coupled MRM with PIS approach could provide both qualitative and quantitative results without the need of repetitive analyses. PMID- 21035601 TI - Proteomic identification of salivary transferrin as a biomarker for early detection of oral cancer. AB - Oral cancer has a low five-year survival rate. Early detection of oral cancer could reduce the mortality and morbidity associated with this disease. Saliva, which can be sampled non-invasively and is less complex than blood, is a good potential source of oral cancer biomarkers. Proteomic analysis of saliva from oral cancer patients and control subjects was performed to identify salivary biomarkers of early stage oral cancer in humans. The protein profile of pooled salivary samples from patients with oral squamous cell carcinoma (OSCC) or OSCC free control subjects was analyzed using two-dimensional gel electrophoresis (2DE) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) analyses. Potential biomarkers were verified by Western blotting and ELISA assays. Transferrin levels were elevated in the saliva of OSCC patients as determined using 2DE followed by MALDI-TOF MS and confirmed by MALDI-TOF/TOF MS, Western blotting and ELISA. The increase in salivary transferrin levels in OSCC patients strongly correlated with the size and stage of the tumor. The area under the receiver-operating characteristics curves showed that salivary transferrin-based ELISA was highly specific, sensitive and accurate for the early detection of oral cancer. We have identified salivary transferrin as a biomarker for the detection of early stage oral cancer. This finding provides a promising basis for the development of a non-invasive diagnostic test for early stage oral cancer. PMID- 21035603 TI - Laser induced-thermal lens spectrometry in combination with dispersive liquid liquid microextraction for trace analysis. AB - A new combination method including laser induced-thermal lens spectrometry (LI TLS) and dispersive liquid-liquid micro extraction (DLLME) was developed and used for determination and preconcentration of trace amount of lead in liquid samples. Thermal lens spectrometry is suitable for determination of analyte after DLLME because of the low volume of the remained phase after DLLME and increasing of the enhancement factor for the non polar organic solvents. Non polar organic solvents have the ideal conditions for this combination because of low thermal conductivity and large variation in refractive index with temperature. In this method; ethanol, carbon tetrachloride and 1,5-diphenyl thiocarbazone (dithizone), were used as disperser solvent, extraction solvent and chelating agent, respectively. Some effective parameters on the micro extraction, complex formation and combination were selected and optimized. Under optimum conditions, the calibration graphs were linear in the range of 0.1-75 MUg L(-1) with the detection limit of 0.01 MUg L(-1). The relative standard deviation (RSD) for 5 and 50 MUg L(-1) of lead was 3.2 and 2.5, respectively. The enhancement factor of 1000 was obtained from a sample volume of 10.0 mL and determination volume of 25 MUL. DLLME/LI-TLS method was applied to the analysis of human blood serums and real water samples. Accuracy of the method was proved by using of standard reference materials. Also, the proposed method was compared with other trace analysis methods. PMID- 21035602 TI - Absolute quantification method and validation of airborne snow crab allergen tropomyosin using tandem mass spectrometry. AB - Measuring the levels of the major airborne allergens of snow crab in the workplace is very important in studying the prevalence of crab asthma in workers. Previously, snow crab tropomyosin (SCTM) was identified as the major aeroallergen in crab plants and a unique signature peptide was identified for this protein. The present study advances our knowledge on aeroallergens by developing a method of quantification of airborne SCTM by using isotope dilution mass spectrometry. Liquid chromatography tandem mass spectrometry was developed for separation and analysis of the signature peptides. The tryptic digestion conditions were optimized to accomplish complete digestion. The validity of the method was studied using international conference on harmonization protocol, Where 2-9% for CV (precision) and 101-110% for accuracy, at three different levels of quality control. Recovery of the spiked protein from PTFE and TopTip filters was measured to be 99% and 96%, respectively. To further demonstrate the applicability and the validity of the method for real samples, 45 kg of whole snow crab were processed in an enclosed (simulated) crab processing line and air samples were collected. The levels of SCTM ranged between 0.36-3.92 MUg m(-3) and 1.70-2.31 MUg m(-3) for butchering and cooking stations, respectively. PMID- 21035605 TI - Full-range optical pH sensor based on imaging techniques. AB - A new colour-based disposable sensor array for a full pH range (0-14) is described. The pH sensing elements are a set of different pH indicators immobilized in plasticized polymeric membranes working by ion-exchange or co extraction. The colour changes of the 11 elements of the optical array are obtained from a commercial scanner using the hue or H component of the hue, saturation, value (HSV) colour space, which provides a robust and precise parameter, as the analytical parameter. Three different approaches for pH prediction from the hue H of the array of sensing elements previously equilibrated with an unknown solution were studied: Linear model, Sigmoid competition model and Sigmoid surface model providing mean square errors (MSE) of 0.1115, 0.0751 and 0.2663, respectively, in the full-range studied (0-14). The performance of the optical disposable sensor was tested for pH measurement, validating the results against a potentiometric reference procedure. The proposed method is quick, inexpensive, selective and sensitive and produces results similar to other more complex optical approaches for broad pH sensing. PMID- 21035606 TI - Counting bacteria on a microfluidic chip. AB - This paper reports a lab-on-a-chip device that counts the number of bacteria flowing through a microchannel. The bacteria number counting is realized by a microfluidic differential Resistive Pulse Sensor (RPS). By using a single microfluidic channel with two detecting arm channels placed at the two ends of the sensing section, the microfluidic differential RPS can achieve a high signal to-noise ratio. This method is applied to detect and count bacteria in aqueous solution. The detected RPS signals amplitude for Pseudomonas aeruginosa ranges from 0.05 V to 0.17 V and the signal-to-noise ratio is 5-17. The number rate of the bacteria flowing through the sensing gate per minute is a linear function of the sample concentration. Using this experimentally obtained correlation curve, the concentration of bacteria in the sample solution can be evaluated within several minutes by measuring the number rate of the bacteria flowing through the sensing gate of this microfluidic differential RPS chip. The method described in this paper is simple and automatic, and have wide applications in determining the bacteria and cell concentrations for microbiological and other biological applications. PMID- 21035604 TI - Wavelet analysis used for spectral background removal in the determination of glucose from near-infrared single-beam spectra. AB - Wavelet analysis is developed as a preprocessing tool for use in removing background information from near-infrared (near-IR) single-beam spectra before the construction of multivariate calibration models. Three data sets collected with three different near-IR spectrometers are investigated that involve the determination of physiological levels of glucose (1-30 mM) in a simulated biological matrix containing alanine, ascorbate, lactate, triacetin, and urea in phosphate buffer. A factorial design is employed to optimize the specific wavelet function used and the level of decomposition applied, in addition to the spectral range and number of latent variables associated with a partial least-squares calibration model. The prediction performance of the computed models is studied with separate data acquired after the collection of the calibration spectra. This evaluation includes one data set collected over a period of more than 6 months. Preprocessing with wavelet analysis is also compared to the calculation of second derivative spectra. Over the three data sets evaluated, wavelet analysis is observed to produce better-performing calibration models, with improvements in concentration predictions on the order of 30% being realized relative to models based on either second-derivative spectra or spectra preprocessed with simple additive and multiplicative scaling correction. This methodology allows the construction of stable calibrations directly with single-beam spectra, thereby eliminating the need for the collection of a separate background or reference spectrum. PMID- 21035607 TI - Highly sensitive trace analysis of paraquat using a surface-enhanced Raman scattering microdroplet sensor. AB - We report a rapid and highly sensitive trace analysis of paraquat (PQ) in water using a surface-enhanced Raman scattering (SERS)-based microdroplet sensor. Aqueous samples of PQ, silver nanoparticles, and NaCl as the aggregation agent were introduced into a microfluidic channel and were encapsulated by a continuous oil phase to form a microdroplet. PQ molecules were adsorbed onto particle surfaces in isolated droplets by passing through the winding part of the channel. Memory effects, caused by the precipitation of nanoparticle aggregates on channel walls, were removed because the aqueous droplets were completely isolated by a continuous oil phase. The limit of detection (LOD) of PQ in water, determined by the SERS-based microdroplet sensor, was estimated to be below 2*10(-9) M, and this low detection limit was enhanced by one to two orders of magnitude compared to conventional analytical methods. PMID- 21035608 TI - Selection of aptamers for a non-DNA binding protein in the context of cell lysate. AB - Aptamer-facilitated Protein Isolation from Cells (AptaPIC) is a recently introduced method that allows, in particular, generation of aptamers for a protein target in a context of a crude cell lysate. The approach enables efficient, tag-free, affinity purification of target proteins which are not available in a pure form a priori, and for which no affinity ligands are available. In the proof-of-principle work, AptaPIC was used to develop aptamers for and purify MutS, a DNA mismatch repair protein. The DNA-binding nature of MutS raised concerns that AptaPIC was not a generic technique and could be inapplicable to protein targets that do not possess native nucleic acid-binding properties. Here we prove that these concerns are invalid. We used AptaPIC to generate pools of aptamers for human Platelet-Derived Growth Factor chain B (PDGF B) protein, a non-DNA binding protein, in the context of a bacterial cell lysate, and subsequently purify it from the same lysate. Within a small number of rounds, the efficiencies of aptamer selection were similar in conventional Systematic Evolution of Ligands by Exponential Enrichment (SELEX) for pure protein and in AptaPIC for protein in the cell lysate. The conventional selection approach resulted in an aptamer pool with an EC(50) value of 2.0+/-0.1 MUM, while the AptaPIC selection approach resulted in a pool with an EC(50) value of 3.9+/-0.4 MUM. Our results clearly demonstrate that selection of aptamers for proteins in the cell lysate is not only realistic but also efficient. PMID- 21035610 TI - Depression vulnerability moderates the effects of cognitive behavior therapy in a randomized controlled trial for smoking cessation. AB - Several clinical trials have tested the hypothesis that smoking cessation treatments with a mood management component derived from cognitive behavior therapy (CBT) for depression would be specifically effective for depression vulnerable smokers, with mixed results. This trial addressed methodological concerns with some of the previous studies to clarify whether depression vulnerability does in fact moderate CBT smoking cessation outcome. The study compared 8-session group CBT with a time-matched comparison group condition in a sample of 100 cigarette smokers randomized to treatment condition. Each treatment group was led by one of 7 American University clinical psychology graduate students; therapists were crossed with treatment conditions. Outcome (7-day point prevalence abstinence) was evaluated 1 month and 3 months after quit date. Baseline self-reported depression vulnerability (sample median split on the Depression Proneness Inventory) moderated treatment response, such that more depression-prone smokers fared better in CBT whereas less depression-prone smokers fared better in the comparison condition. These results may have implications for determining when to use CBT components in smoking cessation programs. PMID- 21035609 TI - A randomized clinical trial of a brief, problem-focused couple therapy for depression. AB - The aim of this study was to evaluate a brief couple therapy for depression targeted for mildly discordant or nondiscordant couples struggling with the negative impact of depression. Subjects included women with major depression or dysthymia who had husbands without clinical depression. Thirty-five couples were randomly assigned to the 5-week intervention (n=18) or a waitlist control group (n=17), and followed up 1 and 3 months later. Results showed a significant effect of treatment in reducing women's depressive symptoms, with 67% of women improved and 40% to 47% recovered at follow-up, compared to only 17% improved and 8% recovered among women in the control group. Treatment was also effective in secondarily improving women's marital satisfaction, reducing husbands' levels of psychological distress and depression-specific burden, and improving both partners' understanding and acceptance of depression. The treatment was implemented in five 2-hour sessions, representing an efficient, cost-effective approach. Findings support the growing utility of brief, problem-focused couple interventions that simultaneously target depression, relational functioning, and psychological distress experienced by the loved ones of depressed persons. PMID- 21035611 TI - Anxiety as a context for understanding associations between hypochondriasis, obsessive-compulsive, and panic attack symptoms. AB - In the context of the integrative model of anxiety and depression, we examined whether the essential problem of hypochondriasis is one of anxiety. When analyzed, data from a large nonclinical sample corresponded to the integrative model's characterization of anxiety as composed of both broad, shared and specific, unique symptom factors. The unique hypochondriasis, obsessive compulsive, and panic attack symptom factors all had correlational patterns expected of anxiety with the shared, broad factors of negative emotionality and positive emotionality. A confirmatory factor analysis showed a higher-order, bifactor model was the best fit to our data; the shared and the unique hypochondriasis and anxiety symptom factors both contributed substantial variance. This study provides refinements to an empirically based taxonomy and clarifies what hypochondriasis is and, importantly, what it is not. PMID- 21035612 TI - Disgust vulnerability and symptoms of contamination-based OCD: descriptive tests of incremental specificity. AB - The present investigation examines the incremental association between disgust propensity and sensitivity and contamination-based obsessive-compulsive disorder (OCD) symptoms. Structural equation modeling in Study 1 indicated that general disgust was related to contamination fear even when controlling for negative affect in a nonclinical sample. Evidence was also found for a model in which the effect of negative affect on contamination fear is mediated by general disgust. Study 1 also showed that both disgust sensitivity and disgust propensity uniquely predicted contamination fear when controlling for negative affect. Growth curve analyses in Study 2 indicated that higher baseline contamination fear is associated with less reduction in contamination fear over a 6-week period as disgust sensitivity increases even when controlling for negative affect. Lastly, disgust propensity was associated with concurrent levels of excessive washing symptoms among patients with OCD in Study 3 when controlling for depression. Implications of these findings from nonclinical, analogue, and clinical samples for future research on the specificity of disgust-related vulnerabilities in the etiology of contamination concerns in OCD are discussed. PMID- 21035613 TI - Parenting cognitions and treatment beliefs as predictors of experience using behavioral parenting strategies in families of children with attention deficit/hyperactivity disorder. AB - We tested a model of mothers' parenting efficacy and attributions for child ADHD behaviors as predictors of experiences with behavioral treatment. The model proposed that mothers' beliefs regarding the acceptability and effectiveness of behavioral strategies would intervene between mothers' cognitions about parenting and child behavior and their treatment experiences. Participants were 101 mothers of 5- to 10-year-old children (82% male) with ADHD. Mothers reported their parenting efficacy and attributions for child behavior, and then received a single session of treatment teaching 2 behavior management strategies. Then, mothers reported their beliefs regarding the acceptability and effectiveness of these strategies. A follow-up phone interview 1 week later assessed mothers' experiences in using the behavioral strategies. The overall model fit the data. Attributions of child ADHD behavior as more pervasive, enduring, and within the child's control were related to seeing behavioral treatment as more acceptable, but neither attributions nor treatment acceptability predicted treatment experience. However, mothers with higher parenting efficacy viewed the behavioral strategies as more likely to be effective, and this pathway significantly predicted positive treatment experience. Implications for understanding the variables that contribute to parental decision-making and treatment participation for childhood ADHD are considered. PMID- 21035614 TI - A taxometric study of hypochondriasis symptoms. AB - Hypochondriasis has been conceptualized as both a distinct category that is characterized by a disabling illness preoccupation and as a continuum of health concerns. Empirical support for one of these theoretical models will clarify inconsistent assessment approaches and study designs that have impeded theory and research. To facilitate progress, taxometric analyses were conducted to determine whether hypochondriasis is best understood as a discrete category, consistent with the DSM, or as a dimensional entity, consistent with prevailing opinion and most self-report measures. Data from a large undergraduate sample that completed 3 hypochondriasis symptom measures were factor analyzed. The 4 factor analytically derived symptom indicators were then used in these taxometric analyses. Consistent with our hypotheses and existing theory, results supported a dimensional structure for hypochondriasis. Implications for the conceptualization of hypochondriasis and directions for future study are discussed. PMID- 21035615 TI - Dimensional, categorical, or dimensional-categories: testing the latent structure of anxiety sensitivity among adults using factor-mixture modeling. AB - The present study tested multiple, competing latent structural models of anxiety sensitivity (AS), as measured by the Anxiety Sensitivity Index-3 (ASI-3; Taylor et al., 2007). Data were collected from 3 sites in North America (N=634). Participants were predominantly university students (M=21.3 years, SD=5.4). ASI-3 data were evaluated using an integration of mixture modeling and confirmatory factor analysis-factor mixture modeling (FMM; Muthen, 2008). Results supported a 2-class 3-factor partially invariant model of AS. Specifically, the FMM analyses indicated that AS is a taxonic (two-class) variable, and that each categorical class has a unique multidimensional factor structure. Consistent with the specific point-prediction regarding the hypothesized parameters of the putative latent class variable, FMM indicated that the putatively "high-risk" subgroup of cases or latent form of AS composed approximately 12% of the studied sample whereas the putatively "normative" subgroup of cases or latent form of AS composed 88% of the sample. In addition, the AS Physical and Psychological Concerns subscales, but not the Social Concerns subscale, most strongly discriminated between the two latent classes. Finally, comparison of continuous levels of AS Physical and Psychological Concerns between FMM-derived AS latent classes and independent clinical samples of patients with anxiety disorders provided empirical support for the theorized taxonic-dimensional model of AS and anxiety psychopathology vulnerability. Findings are discussed in regard to the implications of this and related research into the nature of AS and anxiety psychopathology vulnerability. PMID- 21035616 TI - A randomized controlled effectiveness trial of parent management training with varying degrees of therapist support. AB - This study examined the effectiveness of a Swedish parent management training (PMT) intervention for parents of children aged 3 to 10 within the context of regular social service. Self-referred parents of 159 children (aged 3 to 10) with conduct problems were randomly assigned to either 11 practitioner-assisted group sessions (PMT-P), or a single instructional workshop followed by self administration of the training material (PMT-S), or a waitlist control group. Intent-to-treat analyses showed that both PMT-P and PMT-S improved parent competence and reduced child conduct problems compared to the waitlist at posttest. Both training conditions showed further significant improvements at the 6-month follow-up. In direct comparison, PMT-P was superior to PMT-S on measures of child conduct problems at both posttest and follow-up. Improvement in child conduct was mediated by improvement in parent competencies and homework fidelity. The findings in this study have implications for large-scale dissemination of parent management training through different means of delivery. PMID- 21035617 TI - Is it the symptom or the relation to it? Investigating potential mediators of change in acceptance and commitment therapy for psychosis. AB - Cognitive and behavioral interventions have been shown to be efficacious when used as an adjunct to pharmacotherapy for psychotic disorders. However, little previous research has investigated potential mediators of change in psychological treatments for psychosis. Acceptance and mindfulness-based therapies do not focus on directly reducing the psychotic symptoms themselves, but instead attempt to alter the patient's relationship to symptoms to decrease their negative impact. The current study examined this issue with data from a previously published randomized trial comparing brief treatment with Acceptance and Commitment Therapy (ACT) versus treatment as usual for hospitalized patients with psychotic symptoms (Gaudiano & Herbert, 2006a). Results showed that the believability of hallucinations at posttreatment statistically mediated the effect of treatment condition on hallucination-related distress. Hallucination frequency did not mediate outcome. The current study is a first step toward understanding the potential mechanisms of action in psychological treatments for psychosis. PMID- 21035618 TI - Social anxiety, reasons for drinking, and college students. AB - Recent research suggests that social anxiety may be associated with higher rates of alcohol problems in women, yet may be associated with lower levels of drinking in men. The current study investigated putative mechanisms that may underlie potential gender differences in the social anxiety-alcohol relationship. One hundred and eighteen college students (61.0% women) completed an interview assessing drinking behaviors and questionnaires measuring social anxiety, drinking motives, and drinking situations. Although college men and women both reported similar frequencies of drinking in positive situations and to enhance positive emotions, women reported drinking more often in negative situations and to cope with aversive emotions than men. Mediated moderation analyses suggested that women with social anxiety may be at greater risk of encountering adverse consequences because of their likelihood to drink to conform or to cope with the aversive affect they experience in negative situations. Conversely, when men experience high rates of adverse consequences, it may be due to drinking greater quantities of alcohol in positive situations. Highly socially anxious college men may drink less alcohol and experience fewer adverse consequences than their nonanxious or mildly anxious counterparts because they may find themselves in positive situations and drinking to enhance positive feelings less often, potentially due to avoidant behavior. These findings may help to explain why social anxiety serves as a potential risk factor for alcohol-related problems for college women, but a protective factor for college men. PMID- 21035619 TI - Anxiety symptomatology: the association with distress tolerance and anxiety sensitivity. AB - Research focused on psychological risk factors for anxiety psychopathology has led to better conceptualization of these conditions as well as pointed toward preventative interventions. Anxiety sensitivity (AS) has been well-established as an anxiety risk factor, while distress tolerance (DT) is a related construct that has received little empirical exploration within the anxiety psychopathology literature. The current investigation sought to extend the existing literature by examining both DT and the relationship between DT and AS across a number of anxiety symptom dimensions, including panic, generalized anxiety, social anxiety, and obsessive-compulsive anxiety. Participants (N=418) completed a number of measures that assessed DT, AS, anxiety symptomatology, and negative affect. Findings indicated that DT was uniquely associated with panic, obsessive compulsive, general worry, and social anxiety symptoms, but that DT and AS were not synergistically associated with each of these symptom dimensions. These findings indicate that an inability to tolerate emotional distress is associated with an increased vulnerability to experience certain anxiety symptoms. PMID- 21035620 TI - Cognitive processing specificity of anxious apprehension: impact on distress and performance during speech exposure. AB - The present study examined the impact of different modes of processing anxious apprehension on subsequent anxiety and performance in a stressful speech task. Participants were informed that they would have to give a speech on a difficult topic while being videotaped and evaluated on their performance. They were then randomly assigned to one of three conditions. In a specific processing condition, they were encouraged to explore in detail all the specific aspects (thoughts, emotions, sensations) they experienced while anticipating giving the speech; in a general processing condition, they had to focus on the generic aspects that they would typically experience during anxious anticipation; and in a control, no processing condition, participants were distracted. Results revealed that at the end of the speech, participants in the specific processing condition reported less anxiety than those in the two other conditions. They were also evaluated by judges to have performed better than those in the control condition, who in turn did better than those in the general processing condition. PMID- 21035621 TI - Emotion regulation difficulties in trauma survivors: the role of trauma type and PTSD symptom severity. AB - Two different hypotheses regarding the relationship between emotion regulation and PTSD are described in the literature. First, it has been suggested that emotion regulation difficulties are part of the complex sequelae of early-onset chronic interpersonal trauma and less common following late-onset or single-event traumas. Second, PTSD in general has been suggested to be related to emotion regulation difficulties. Bringing these two lines of research together, the current study aimed to investigate the role of trauma type and PTSD symptom severity on emotion regulation difficulties in a large sample of trauma survivors (N=616). In line with the hypotheses, PTSD symptom severity was significantly associated with all variables assessing emotion regulation difficulties. In addition, survivors of early-onset chronic interpersonal trauma showed higher scores on these measures than survivors of single-event and/or late-onset traumas. However, when controlling for PTSD symptom severity, the group differences only remained significant for 2 out of 9 variables. The most robust findings were found for the variable "lack of clarity of emotions." Implications for future research, theoretical models of trauma-related disorders, and their treatment will be discussed. PMID- 21035622 TI - What can be inferred from the interruption of the semagacestat trial for treatment of Alzheimer's disease? PMID- 21035624 TI - A positron emission tomography study examining the dopaminergic activity of armodafinil in adults using [11C]altropane and [11C]raclopride. AB - BACKGROUND: Armodafinil, prescribed principally to treat narcolepsy, is undergoing assessment of therapeutic potential for other neuropsychiatric disorders and medical conditions. The neurochemical substrates and mechanisms of armodafinil are unresolved. We investigated the hypothesis that armodafinil enhances wakefulness by modulating the activities of the dopamine transporter (DAT). With positron emission tomography imaging, we determined DAT occupancy and changes in extracellular dopamine by armodafinil in vivo. METHODS: Twelve subjects were enrolled. Plasma armodafinil levels were obtained. In vivo armodafinil occupancy of the DAT in striatum was detected by [11C]altropane and changes in extracellular dopamine were detected by indirect displacement of [11C]raclopride in human subjects at different times after drug administration. RESULTS: Armodafinil (100 mg by mouth [PO]) occupied striatal DAT (34.0 +/- 9.0% at 1 hour, 40.4 +/- 9.5% at 2.5 hours, n = 6) and 250 mg occupied striatal DAT (60.5 +/- 7.4% at 1 hour, 65.2 +/- 6.1% at 2.5 hours, n = 6). In addition, armodafinil was associated with changes in extracellular dopamine (17.8 +/- 30.1% [100 mg PO] and 7.0 +/- 8.6% [250 mg PO] at 2.5 hours, n = 6). CONCLUSIONS: Occupancy of the DAT and changes in extracellular dopamine in vivo further implicates the actions of armodafinil on DAT as a potential candidate for its therapeutic improvement of wakefulness and other conditions. PMID- 21035625 TI - [Female sexual dysfunctions: myths, realities and perspectives]. PMID- 21035623 TI - YKL-40: a novel prognostic fluid biomarker for preclinical Alzheimer's disease. AB - BACKGROUND: Disease-modifying therapies for Alzheimer's disease (AD) would be most effective during the preclinical stage (pathology present, cognition intact) before significant neuronal loss occurs. Therefore, biomarkers that detect AD pathology in its early stages and predict dementia onset and progression will be invaluable for patient care and efficient clinical trial design. METHODS: AD associated changes in cerebrospinal fluid (CSF) were measured using two dimensional difference gel electrophoresis and liquid chromatography tandem mass spectrometry. Subsequently, CSF YKL-40 was measured by enzyme-linked immunosorbent assay in the discovery cohort (n = 47), validation cohort (n = 292) with paired plasma samples (n = 237), frontotemporal lobar degeneration (n=9) [corrected], and progressive supranuclear palsy (PSP; n = 6). Immunohistochemistry was performed to identify source(s) of YKL-40 in human AD brain. RESULTS: Discovery and validation cohorts, showed higher mean CSF YKL-40 in very mild and mild AD-type dementia (Clinical Dementia Rating [CDR] 0.5 and 1) versus control subjects (CDR 0) and PSP subjects. Importantly, CSF YKL-40/Abeta42 ratio predicted risk of developing cognitive impairment (CDR 0 to CDR > 0 conversion), as well as the best CSF biomarkers identified to date, tau/Abeta42 and p-tau 181/Abeta42. Mean plasma YKL-40 was higher in CDR 0.5 and 1 versus CDR 0, and correlated with CSF levels. YKL-40 immunoreactivity labeled astrocytes near a subset of amyloid plaques, implicating YKL-40 in the neuroinflammatory response to Abeta deposition. CONCLUSIONS: These data demonstrate that YKL-40, a putative indicator of neuroinflammation, is elevated in AD and, together with Abeta42, has potential prognostic utility as a biomarker for preclinical AD. PMID- 21035626 TI - [The Arnett Inventory of Sensation Seeking (AISS): a French-speaking validation and psychometric examination in young students]. AB - INTRODUCTION: In French-speaking countries, the concept of sensation seeking has been most widely assessed using the Zuckerman Sensation Seeking Scale form V (SSS), since this instrument was validated (in French) more than 15 years ago. This instrument has received several criticisms which limit the internal and external consistencies. Indeed, five limitations of conception and form could reduce the fact that many researchers have found the SSSV to be valid and useful and, more importantly, the conclusions that can be drawn from studies in which it has been used (e.g; tautological relationships, a forced-choice format, language of some items is out-of-date). Arnett thus developed a new measurement (Arnett Inventory of Sensation Seeking, AISS) based on a new conceptualization of sensation seeking, which is characterized by the need for novelty and intensity of stimulation, whereas sensation seeking, as developed by Zuckerman, is marked by a need for novelty and complexity of stimulation. The AISS has been translated and validated in Spanish and in German. Both studies found support for the bi dimensional structure of the instrument. Currently, there is no French-speaking version of the AISS, and because of the cultural differences between English- and French-speaking populations, we cannot simply translate the instrument without examining the reliability and the factorial validity. Hence, we followed the seven steps of the cross-cultural validation methodology for psychological questionnaires presented by Vallerand. METHOD: Questionnaires were distributed to 782 young adults. Out of these questionnaires, 737 (94%) were returned. One hundred and sixteen questionnaires were removed because of missing data. Thus, a total of 621 young adults were included in the study. They were aged from 18 to 28 years (M=23.32, SD=2.79). They completed the SSS and the AISS. We conducted a confirmatory factor analysis (CFA) on the data set, using Amos 6.0, to assess the validity of the bi-dimensional structure; we also examined the internal consistencies, and tested the potential gender differences. RESULTS: The analyses show that the fit indices, associated with the model with 20 items proposed by Arnett, were poor. We therefore had to modify it and delete some items in order to provide a more satisfactory account of the data. The fit indices from the confirmatory factor analysis were adequate for a two-factor structure with six items on each subscale. Pearson's correlation coefficients supported convergent validity of the questionnaire. Internal consistency reliabilities Cronbach's alpha were calculated for each of the factors and for the total scale. The reliability coefficients for the Intensity and Novelty subscales were 0.621 and 0.567, respectively, whereas the reliability of the overall scale was 0.646. In order to assess the differences between both sexes, we carried out a multivariate analysis of variance with gender as independent variables, and intensity, novelty and the total score of the revised AISS as dependent variables. Men scored higher than women on the Total Scale and on the Intensity subscale, but no gender relationship was found on Novelty subscale. DISCUSSION: These findings replicated research supporting the construct validity and reliability of the AISS in previous psychometric examinations. The results of this preliminary study yielded sufficient support for the validity of the French translation of the AISS, but further analyses, such as test-retest reliability and discriminant validity should be conducted. PMID- 21035627 TI - [Course of borderline personality disorder: literature review]. AB - INTRODUCTION: Borderline personality disorder (BPD) is a serious mental disorder associated with severe emotional, behavioral, cognitive and interpersonal dysfunction, extensive functional impairment and frequent self-destructive behaviour, including deliberate self-harm and suicidal behaviour. For quite some time, BPD has been viewed as a chronic disorder and borderline patients as extremely difficult to treat, doomed to a life of misery. However, those views are changing and there is an increasing recognition that BPD has a far more benign course than previously thought. The purpose of this study is to show how those views changed over time by reviewing longitudinal studies of the course of BPD. METHODS: We have reviewed the literature published from 1968 to March 2009, using the following key words: borderline personality disorder, outcome, follow up studies with some additional references. RESULTS: The aim of the longitudinal studies conducted prior to the DSM definition of BPD criteria was to determine whether borderline patients could become psychotic over time, but no such evidence was found even though their functioning was at a relatively low level. The studies conducted after the introduction of BPD in the DSM in 1980 tested the stability and the specificity of BPD diagnosis, concluding that the criteria were relatively stable in the short run since the majority of patients continued to meet them at the follow-up assessments. However, those studies had many methodological drawbacks which limited their generalizability such as small sample sizes, high attrition rates, the absence of comparison groups, etc. Four retrospective studies of the 15-year outcome of borderline patients obtained virtually identical results despite methodological differences, showing that the global functioning of borderline patients improved substantially over time with mean scores of the GAF scale falling within a mild range of impairment. One 27 year retrospective study showed that borderline patients continued to improve as they grew older, only 8% of the cohort still meeting criteria for BPD. Two recent carefully designed prospective studies showed that the majority of BPD patients experienced a substantial reduction in their symptoms far sooner than previously expected. After six years, 75% of patients diagnosed with BPD severe enough to be hospitalized achieve remission by standardized diagnostic criteria and after 10 years, the remission rate raises up to 88%. Recurrences are rare, no more than 6% over six years. The dramatic symptoms (suicidal behaviour, self-mutilation, queasy psychotic thoughts) resolve relatively quickly, but abandonment concerns, feeling of emptiness and vulnerability to dysphonic states is likely to remain in at least half the patients. DISCUSSION: This contrasts with the natural course of many Axis I disorders, such as mood disorders, where improvement rates may be somewhat higher and more rapid but recurrences are more frequent. The findings of longitudinal studies raise doubts about the validity of the definition in the DSM, which implies that personality disorders must necessarily be chronic. However, it should be noted that even the most encouraging findings do not show full recovery since the majority of patients seem to suffer from some residual symptoms. CONCLUSION: These findings have very important clinical implications and borderline patients should be told that they can expect improvement, no matter how intense their current emotional pain. However, we still lack evidence based findings on mechanisms that lie behind the recovery process in BPD. Future research should explore the mechanisms of recovery in BPD. PMID- 21035628 TI - [Psychometric properties of the French version of the Wender Utah Rating Scale and Brown's Attention Deficit Disorders Scale for adults]. AB - OBJECTIVES: The objective of this work was to analyse the factorial structure of the two following instruments: (1) the Wender Utah Rating Scale (WURS) evaluates the Attention Deficit Hyperactivity Disorders (ADHD) for adults, with 25 items: the subjects describe their own childhood behaviour when they were 7 years old, (from few to very much, 0 to 4). The items are grouped in four clusters: affects and emotional problems; impulsivity and conduct disorders; impulsivity hyperactivity; and difficulties in attention. A score of 46 or more strongly suggests diagnosis of a hyperactivity disorder during infancy; (2) Brown's (1996) Attention Deficit Disorders Scale (ADD) is a 40-item self-report. This scale is composed of a range of symptoms beyond the DSM-IV inattention criteria for ADHD. A score of 50 or more is strongly suggestive of ADD. The five clusters of this scale are: organizing and activating work; sustaining attention and concentration; sustaining energy and effort; managing affective interference; utilizing "working memory" and accessing recall. METHODS: For comparative purpose, we also used the Adult Self-Report Scale (ASRS), which evaluates ADHD with six items and accepts a cut-off of four or more; the Barratt Impulsivity Scale, and the Personality Inventory Revised, essentially with the neuroticism cluster. A total of 259 adult subjects were enrolled in this study and allocated to three groups: healthy subjects, depressive patients and alcoholic patients. RESULTS: This study indicates that the internal consistency for the French version of the ADD and WURS scales is adequate (alpha=0.8-0.9). The WURS and ADD scales are not fully validated, as both sensitivity to change and concurrent validity for all groups are missing. However, these adapted versions are interesting because they facilitate the use of the questionnaires for research and clinical assessment within healthy general and clinical populations. The study confirmed the psychometric properties of the two scales evaluating ADHD: Wender's Hyperactivity Scale during childhood and Brown's Attention Deficit Disorder Scale for adults (ADD). A larger patient sample would permit clearer conclusions. Nevertheless, the obtained results are very encouraging. DISCUSSION: The ASRS has already been validated. It has shown its utility as a screening tool (well correlated with the Brown's ADD Scale) and gives us a better understanding of the nature of difficulties met by patients in terms of attention. We would like to complete this study in the short-term by increasing the patient sample size and harmonizing evaluation instruments by applying the three scales (ADD, WURS and ASRS) within the three groups. Our results support the idea that the clinical population showed an elevated presence of ADD and this disorder needs to be assessed. PMID- 21035629 TI - [Psychometric properties of a French adaptation of the Tinnitus Handicap Inventory]. AB - INTRODUCTION: Tinnitus is a subjective phenomenon and in the majority of cases it is impossible to objectify it. The patient's self-evaluation using questionnaires and rating scales is the only way to quantify this symptom. Among the most widely used tools is the Tinnitus Handicap Inventory (THI). This questionnaire permits the practitioner to quantify the severity of tinnitus and measure the psycho emotional and functional components of the tinnitus related handicap. It has been translated and validated in many languages. However, there is no French version of the THI. The reliability of the THI as a powerful clinical tool for tinnitus evaluation, and the lack of a French version of this questionnaire led us to translate it into French. The goal of this study was to validate our French adaptation of the THI (fTHI) for the management of French-speaking tinnitus sufferers. This is also essential for an effective international cooperation. METHODS: The fTHI was presented to a sample of 174 patients (63% men and 34% women) who had consulted our IMERTA Tinnitus Centre from June 2007 to July 2008. All patients reported tinnitus that had persisted for at least six months (average duration: 5.9 +/- 4.3 years) as their primary complaint. The mean age of the sample was 54.2 +/- 16.4 years, ranging from 22 to 84. The patients did not present any linguistic or mental problems likely to compromise their capacities to answer French questionnaires. During the first visit, before the consultation with the doctor, the patients were asked to complete the fTHI, and to evaluate the clearness of items and the ease of answering the questionnaire. Using rating scales, the patients were also asked to evaluate the severity of tinnitus and its impact on their quality of life. Internal consistency reliability of the fTHI and each sub-scale was evaluated using Cronbach's alpha coefficient (alpha). The average values, standard errors and correlations between the items, the scores of fTHI and those of the rating scales were calculated using "Statistica 6" software. The level of significance was set at 0.05. The homogeneity was considered to be satisfactory for alpha greater than 0.8. RESULTS: Ninety-seven percent of the patients answered the totality of the fTHI. Ninety-six percent of them evaluated it as simple, comprehensible and easy to answer. Cronbach's alpha for the fTHI was 0.90 with item/total correlations (p<0.001) ranging from r=0.21 (item n(o) 19) to r=0.71 (items n(o) 17 and 21). Cronbach's alpha for the functional sub-scale was 0.80 with item/total correlations (p<0.001) ranging from r=0.38 (item n(o) 24) and 0.69 (item n(o) 4). Cronbach's alpha for the emotional sub-scale was 0.85 with item/total correlations (p<0.001) ranging from r=0.52 (item n(o) 6) and r=0.78 (item n(o) 21). Cronbach's alpha for the catastrophic sub-scale was 0.49 with item/total correlations (p<0.001) ranging from r=0.51 (item n(o) 19) and 0.63 (item n(o) 23). The total score of the fTHI is correlated significantly (p<0.001) with the functional (r=0.91), emotional (r=0.90) and catastrophic (r=0.69) sub-scales. Correlations between the fTHI and the rating scales vary between 0.26 (p<0.001) and 0.61 (p<0.001). The highest coefficient of correlation is obtained for the "Total score of fTHI"/"Tinnitus impact on quality of life". CONCLUSIONS: Our results show that the French adaptation of the THI and its sub-scales has good internal consistency reliabilities, comparable to those of the original version. Significant inter-correlations are found between the sub scales items, even if they represent three distinct factors. In addition, the fTHI is correlated with the self-report rating scales of the tinnitus's impact on the patient's quality of life and the severity of tinnitus. Thus, the fTHI is a psychometrically robust, reliable and valid measure of tinnitus related handicaps and can be used in a clinical setting to quantify the impact of tinnitus on French-speaking patients' quality of life, and to monitor their progress with specific therapies. PMID- 21035630 TI - [Evolution of the social autonomy scale (EAS) in schizophrenic patients depending on their management]. AB - It is becoming clear to clinicians that functional prognosis is the issue that should be guiding their choice of therapeutic strategy offered to people with schizophrenic disorders. An individual's degree of social autonomy is one of the principal factors determining functional prognosis, and it has become essential to identify the variables that influence it. The ESPASS survey was set up to follow a cohort of 6000 schizophrenic patients in a naturalistic setting, and was conducted over six months by 1170 psychiatrists. Patients were required to meet DSM-IV TR criteria for schizophrenia, with the exception of those suffering from an acute psychotic episode, and to either need a change in their antipsychotic treatment or its initiation. Data collected included patients' sociodemographical characteristics, types of treatment (pharmacological and non-pharmacological), illness characteristics (as determined by the DSM-IV TR criteria), degree of social autonomy (EAS), effectiveness (IAQ scale), overall severity of the illness (CGI - S scale) and patient satisfaction with medical treatment (PASAP self questionnaire). Concerning the non-pharmacological aspects of treatment that offer patients programmes to increase their autonomy, the survey made it possible to collect data describing real practices and to measure the actual availability of rehabilitation services. It has been verified that the sample of psychiatrists included in this survey, as well as the schizophrenic patients under evaluation, were representative of the French psychiatrist and patient populations. Most importantly, the survey made it possible to objectively evaluate the healthcare services available in France. It seems that the vast majority of public-service psychiatrists have access to hospital and ambulatory facilities for treatment (medical-psychological centers, day-care hospitals and rest centers), as well as access to facilities providing simulated real-life activities. Psychiatrists who are private practitioners have less access to such arrangements for their patients. The vast majority of psychiatrists in both categories are unable to offer their patients active rehabilitation techniques: training in social skills (25%), cognitive remediation (16%), cognitive-behavioral therapies (20%), even though psychoeducation is quite widespread (44%). However, the survey demonstrated that the actual use of these methods was much lower still (2%, 1% and 2%, respectively), although the use of alternative facilities to hospitalization was quite high (day-care hospitals 9%, rest-centers 8%). In total, at the end of the study, the proportion of patients benefiting from some kind of programme to increase their level of autonomy was 41%. These results have demonstrated a link between the evolution of patients' clinical symptoms and their social autonomy. Within the findings, the items that varied most were patient's level of personal care and relations with others, whereas the ability to manage resources seems difficult to influence. Moreover, the results have shown that better development of social autonomy is significantly correlated with the prescription of second-generation antipsychotics. Regarding non pharmacological treatment, better development of social autonomy is significantly correlated with setting up programmes to achieve this objective, including the use of active rehabilitation techniques. Overall, the survey confirmed the results of earlier work to validate the scale of social autonomy (EAS), and confirmed the robustness of its objective measurements. PMID- 21035631 TI - [Psychometric properties of the Activities Daily Life Scale (ADL)]. AB - OBJECTIVE: Deficits in social functioning are an important core feature of mental health. Recently in France, the Activities Daily Life (ADL) scale has been proposed by the French authorities to assess social functioning for all hospitalized patients in a psychiatric ward. The perspective is to use this scale in the financing and organization of mental health services in France. The ADL scale is a 6-item (dressing/undressing, walking/mobility, eating/drinking, using toilets, behaviour, relationships/communication) heteroquestionnaire completed by a health care professional at the beginning of each hospitalization, assessing functioning of patients suffering from mental health diseases. However, limited consensus exists on this scale. The psychometric properties of the ADL scale have not been assessed. There is a pressing need for detailed examination of its performance. The aim of this study was to explore ADL psychometric properties in a sample of hospitalized patients in a psychiatric ward. METHOD: We retrospectively analyzed data for all episodes of care delivered to hospitalized patients in a psychiatric ward in our French Public Hospital from January 1, 2008 to June 30, 2008. The study involved retrospective review of administrative and medical databases. The following data were collected: age, gender, diagnoses based on the International Classification of Diseases - 10th version, ADL scale and Assessment of Social Self-Sufficiency scale (ASSS). The psychometric properties were examined using construct validity, reliability, external validity, reproducibility and sensitivity to change. Data analysis was performed using SPSS 15.0 and WINSTEP software. RESULTS: A total of 1066 patients completed the ADL scale. Among them, 49.7% were male, mean age was 36.5 +/- 10.8, and 83.5% were single. Schizophrenia, schizotypal and delusional disorders (40.0%), mood disorders (27.9%) and mental and behavioural disorders due to psychoactive substance use (12%) were the most common diagnoses. Factor analysis with varimax rotation identified a 2-factor structure accounting for 82% of the total variance. The first dimension (ADL 1) comprised four items and represented personal care activities. The second dimension (ADL 2) comprised two items and represented social functioning. A floor effect was reported for ADL 1 and its unidimensionality was not satisfactory: two items showed an INFIT statistic outside the acceptable range. Internal consistency was satisfactory for the two dimensions: each item achieved the 0.40 standard for item-internal consistency. The correlation of each item with its contributory dimension was higher than with the other (item discriminant validity). Cronbach's alpha coefficients ranged over 0.70 in the whole sample. Concerning external validity, positive correlations were not systematically found between ADL and ASSS dimensions. The score of ADL 1 had medium to high correlations with four dimensions scores of the ASSS, while the score of ADL 2 were not at all or weakly correlated with ASSS dimension scores. Globally, ADL did not cover sentimental life and social relationships. There were statistical associations between ADL and age or gender: women and subjects older than 60 had a higher level of dependency. We didn't find any association with marital status or diagnoses. The ADL scale presented a good reproducibility but was not sensitive to change. CONCLUSION: The psychometric properties of the ADL scale were not sufficient for several parameters such as validity or sensitivity to change, contrary to other available French scales. The use of a heteroquestionnaire rather than a self-administered questionnaire should be discussed by professionals and the French authorities. These results should be taken into account in the use of the ADL scale for the economic and administrative management of psychiatry. Further research should be conducted to confirm these results. PMID- 21035632 TI - [Iatrogenic psychiatric-like symptoms recognition]. AB - INTRODUCTION: This article proposes a review of atypical multicentre studies for drug-induced movement disorders (and related psychiatric symptoms) and supersensitivity psychosis. A well-conducted antipsychotic treatment consists of regular attempts to reduce the dose by finding the minimal therapeutic dose. To achieve optimal antipsychotic treatment, it is important to distinguish psychiatric symptoms associated with drug-induced movement disorder(s) (DIMD) or supersensitivity psychosis from true relapse. LITERATURE FINDINGS: Persistent DIMD have been found to be a predictor of supersensitivity psychosis or tardive dyskinesia (DT). DIMD-associated psychiatric symptoms can be classified into three types: directly induced by DIMD; resulting from confounding DIMD with psychiatric symptoms; and supersensitivity symptoms associated with DIMD. Without this distinction, the beneficial effects of antipsychotics are masked by emergent DIMD psychiatric symptoms (as was confounded in the CATIE study). DISCUSSION: A constant decline in the prevalence of TD (hyperkinetic, involuntary and purposeless movement disorder) has been observed since the introduction of atypical antipsychotics. The neurotoxic effects of classical antipsychotics are well documented and their discontinuation is required. However, the risk of TD still exits with atypical antipsychotics and continued surveillance of emerging cases is very important for clinicians. Moreover, a regular evaluation of DIMD and associated psychiatric symptoms is crucial. It is important to underline the fact that DIMD persists with antipsychotics, with significantly higher total PANSS scores than in patients without DIMD. CONCLUSION: Supersensitivity psychosis is a drug-induced psychotic relapse (6 weeks following the decrease or withdrawal of an antipsychotic). Discontinuation syndromes can produce psychiatric symptoms (and be confounded with true relapse), but can be improved more quickly after reintroduction of treatment. Interestingly, various data suggest that lower doses of antipsychotics could prevent such symptoms. Anticonvulsants can be efficient adjuvants in the treatment of psychosis. In the United States, many patients received valproate or gabapentin treatment. These adjuvants, by antikindling effect, can facilitate minimal maintenance drug treatment and be efficient for anxiety. Resistant schizophrenia can be related to supersensitivity psychosis; gabapentin and lamotrigine are effective in this case. PMID- 21035633 TI - [Efficacy of escitalopram vs paroxetine on severe depression with associated anxiety: data from the "Boulenger" study]. AB - Several recent studies have underlined the importance of anxiety in major depressive disorders. It has been shown that anxiety was responsible for worsening of depression and reduction of the efficacy of the antidepressant treatment. While it is well known that SSRI are efficient in treating depression or anxiety disorders, the authors tried to determine the influence of baseline anxiety on the response to SSRI treatment in patients with severe depression receiving either escitalopram or paroxetine. In a 24-week double-blind clinical trial, 459 patients with a primary diagnosis of severe major depressive disorder were randomised to receive escitalopram (20mg) or paroxetine (40mg). Post hoc analyses of efficacy in patients with a baseline HAM-A total score less or equal to 20 (n=171) or greater than 20 (n=280) were based on analysis of covariance. (ANCOVA) (ITT, LOCF). At week 24, the mean change from baseline in MADRS total score was -24.2 for escitalopram-treated patients (n=141) and -21.5 for paroxetine treated patients (n=139) (p<0.05, between both groups) in high baseline anxiety patients (HAM-A>20) and the mean change from baseline in HAM-A total score was -17.4 (escitalopram) and -15.1 (paroxetine) (p<0.05, between both groups). As far as complete remitters (CGI-S=1) after 24-week treatment were concerned, their number was significantly higher with escitalopram in the case of marked baseline anxiety. No difference was shown in the low baseline anxiety group. Looking for the influence of baseline anxiety on SSRI treatment effects, the authors showed that antidepressant efficacy of 20mg escitalopram was better than 40mg paroxetine for patients highly depressed with comorbid anxiety symptoms and that, contrary to paroxetine, escitalopram maintained sustained antidepressant activity in patients featuring increased baseline anxiety levels. PMID- 21035634 TI - [Therapeutic alliance in psychotherapy: the contribution of empirical research]. AB - INTRODUCTION: The therapeutic alliance in psychotherapy refers to the quality of the relationship between therapist and patient, as well as their agreement upon the aims and tasks of the treatment. This concept is widely used in clinical settings and, since the validation of a number of instruments, has become the focus of much research. However, the quantity of experimental evidence now available impedes the dissemination of these findings among clinicians in a concise manner. LITERATURE FINDINGS: The present paper aimed to provide a review of the literature reporting experimental evidence focusing on the therapeutic alliance. In order to do this, findings were organized around four main issues: the relationship between the therapeutic alliance and clinical outcome; the evolution of the therapeutic alliance over time; the mechanism of action by which the therapeutic alliance encourages change, and finally the factors that have been shown to influence the creation and evolution of the alliance. DISCUSSION: This review reveals that the therapeutic alliance is to this day one of the most investigated factors of psychotherapy. The therapeutic alliance enables change to take place during psychotherapy and, along with a number of specific factors, appears to be important for clinical outcome. Over time, the therapeutic alliance has been seen to evolve and several patterns have been identified. A number of characteristics inherent to the patient, the therapist, and even their interaction have been reported to influence the development and strength of the therapeutic alliance. Several hypotheses have been put forward to account for the mechanism by which the therapeutic alliance encourages change. CONCLUSION: The area of research regarding the therapeutic alliance remains dynamic. Despite the present body of knowledge surrounding this concept, a number of research questions await further investigation. PMID- 21035635 TI - Potentiometric and voltammetric polymer lab chip sensors for determination of nitrate, pH and Cd(II) in water. AB - Due to their toxicity to humans and animals, heavy metals and nitrate in groundwater are of particular concern. The combination of high toxicity and widespread occurrence has created a pressing need for effective monitoring and measurement of nitrate and heavy metals in soil pore water and groundwater at shallow depths. In this work, a new electrochemical sensing platform with the self-assembly nanobeads-packed (nBP) hetero columns has been developed for the pH and nitrate measurements. In addition, for on-site determination of cadmium (Cd(II)), a bismuth (Bi(III)) based polymer lab chip sensor using the square-wave anodic stripping voltammetry (SWASV) sensing principle has been designed, fabricated and successfully characterized. Factors affecting sensitivity and precision of the sensor, including deposition potential and deposition time, were studied. Miniaturized electrochemical lab chip sensors could be very valuable in environmental monitoring area due to their many benefits, such as greatly reduced sensing cost, sensing system portability, and ease of use. PMID- 21035637 TI - A dual validation approach to detect anthelmintic residues in bovine liver over an extended concentration range. AB - This paper describes a method for the detection and quantification of 38 residues of the most widely used anthelmintics (including 26 veterinary drugs belonging to the benzimidazole, macrocyclic lactone and flukicide classes) in bovine liver using two different protocols for MRL and non-MRL levels. A dual validation approach was adopted to reliably quantify anthelmintic residues over an extended concentration range (1-3000 MUg kg(-1)). Sample extraction and purification was carried out using a modified QuEChERS method. A concentration step was included when analysing in the low MUg kg(-1) range. Rapid analysis was carried out by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC MS/MS), which was capable of detecting residues to <2 MUg kg(-1). The method has been single-laboratory validated according to the 2002/657/EC guidelines and met acceptability criteria in all but a few cases. The inclusion of 19 internal standards, including 14 isotopically labelled internal standards, improved accuracy, precision, decision limit (CCalpha) and detection capability (CCbeta). PMID- 21035636 TI - Radial basis network analysis of color parameters to estimate lycopene content on tomato fruits. AB - With the purpose of estimating the lycopene concentration in tomato food samples, in an non-destructive way, several types of linear models of color parameters have been tested using individual values of L*, a* and b* values, (a*/b*), (a*(2)/b*(2)) and chroma parameters from tomato juice and fresh tomato fruits obtained with two different apparatus (Minolta CR-200b triestimulus colorimeter and HunterLab LabScan XE). Lycopene concentrations of fresh tomato and tomato juice (used as an input) were analyzed by UV-Vis spectroscopy. For all linear methods applied, the best one to estimate the lycopene concentration in tomato was the L*, a* and b* values of tomato juice measured with Hunter colorimeters (adjusted correlation coefficient, R(a)(2)>0.86 and mean prediction error, MPE<6.59%). Four different RBEF models were designed firstly using three color parameters (L*, a* and b*) designated as "Lab case", and secondly individually by the (a*/b*), (a*(2)/b*(2)) and chroma parameters. The lycopene concentration estimations were carried out with the lowest MPE and highest R(a)(2) values possible. In order to test the reliability of the non-linear models, external validation process was also performed. From the testing of the all non-linear models applied, the RBEF Lab case model was the best to estimate lycopene content from color parameters (L*, a* and b*) using Minolta or Hunter equipments (MPE lower than 0.009 and R(a)(2) higher than 0.997). This was a simple non destructive method for predicting lycopene concentration in tomato fruits and tomato juice, which was reproducible and accurate enough to substitute chemical extraction determinations, and may be a useful tool for tomato industry. PMID- 21035638 TI - Pressurised liquid extraction and quantification of fat-oil in bread and derivatives products. AB - A pressurised liquid extraction (PLE) method for extraction and quantification of total fat and oil in bread and derivatives products has been proposed. Parameters implied in the extraction process; such us temperature, static time, number of extraction cycles, purge time and flush volume; have been optimised using a formal methodology based on statistical experimental design in order to obtain the best results. Moreover, this method has been validated using homemade bread elaborated in the laboratory which contained 9.64 g of olive oil in 100g dry weight. The production and use of an "ad hoc" in-house reference material is just one of the most relevant aspects of this study. The uncertainty estimation has been carried out taking into account all the uncertainty components of the process and it was stated as 4.2%. Finally, the proposed method has been applied to six different Spanish bread derivatives products with different olive oil contents (5-20%) to determine the fat content. PMID- 21035639 TI - Viable but nonculturable cells used in biosensor fabrication for long-term storage stability. AB - In this paper, we first reported the viable but nonculturable (VBNC) cells used for fabricating biosensor. The organic-inorganic hybrid material composed of silica and the grafting copolymer of poly(vinyl alcohol) and 4-vinylpyridine (PVA g-P(4-VP)) was used to immobilize microbial cells for biosensor fabrication. The VBNC cells were formed after the hybrid material dried, showing the cell walls were sacrificed. With the intracellular enzymes as core and the "sacrificed" cell walls as shell, the present VBNC cells maybe considered as a core/shell structure. The extracellular material worked as the scaffold for core/shell structure. The core/shell structure and the scaffold structure were demonstrated by single-cell level image analysis using confocal laser scanning microscopy (CLSM). The electrochemical method was adopted for further examining the enzyme activity of VBNC cells. The VBNC cells did not need nutrient treatment and other physicochemical factors for cell growth, which is a significant contribution for storing biosensor. A glucose-glutamic acid biosensor fabricated by the VBNC cells exhibited long-term storage stability for 100 days. PMID- 21035640 TI - Optimization of temperature-controlled ionic liquid dispersive liquid phase microextraction combined with high performance liquid chromatography for analysis of chlorobenzenes in water samples. AB - Temperature-controlled ionic liquid dispersive liquid phase microextraction (TCIL DLPME) combined with high performance liquid chromatography-diode array detection (HPLC-DAD) was applied for preconcentration and determination of chlorobenzenes in well water samples. The proposed method used 1-butyl-3-methylimidazolium hexafluorophosphate ([C(4)mim][PF(6)]) as the extraction solvent. The effect of different variables on extraction efficiency was studied simultaneously using an experimental design. The variables of interest in the TCIL-DLPME were extraction solvent volume, salt effect, solution temperature, extraction time, centrifugation time, and heating time. The Plackett-Burman design was employed for screening to determine the variables significantly affecting the extraction efficiency. Then, the significant factors were optimized by using a central composite design (CCD) and the response surface equations were developed. The optimal experimental conditions obtained from this statistical evaluation included: extraction solvent volume, 75 MUL; extraction time, 20 min; centrifugation time, 25 min; heating time, 4 min; solution temperature, 50 degrees C; and no addition of salt. Under optimal conditions, the preconcentration factors were between 187 and 298. The limit of detections (LODs) ranged from 0.05 MUg L(-1) (for 1,2-dichlorobenzene) to 0.1 MUg L(-1) (for 1,2,3 trichlorobenzene). Linear dynamic ranges (LDRs) of 0.5-300 and 0.5-500 MUg L(-1) were obtained for dichloro- and trichlorobenzenes, respectively. The performance of the method was evaluated for extraction and determination of chlorobenzenes in well water samples in micrograms per liter and satisfactory results were obtained (RSDs<9.2%). PMID- 21035641 TI - A label-free electrochemical immunoassay for IgG detection based on the electron transfer. AB - In this study, a highly selective, label-free electrochemical immunoassay strategy based on the charge transport through the multilayer films associated with the electrocatalytic reduction of [Fe(CN)(6)](3-) is proposed using human immunoglobulin G (human IgG) as the model analyte. The antibody-antigen complex formed on the sensing interface can efficiently induce change of the surface charge characteristics, the conductivity of multilayer film and/or electron transfer distance, resulting in an immunoreaction signal. The current reduction is proportional to the amount of analyte. Under the optimized experimental conditions, the proposed sensing strategy provides a linear dynamic range from 10 to 10(4) ng mL(-1) and a detection limit of 3 ng mL(-1), indicating an improved analytical performance. This possibly makes it a potential alternative in bioanalysis of proteins and other molecules. PMID- 21035642 TI - Sensitive sandwich immunoassay based on single particle mode inductively coupled plasma mass spectrometry detection. AB - A sensitive sandwich type immunoassay has been proposed with the detection by inductively coupled plasma mass spectrometry (ICP-MS) in a single particle mode (time resolved analysis). The signal induced by the flash of ions ((197)Au(+)) due to the ionization of single Au-nanoparticle (Au-NP) label in the plasma torch can be measured by the mass spectrometer. The frequency of the transient signals is proportional to the concentration of Au-NPs labels. Characteristics of the signals obtained from Au-NPs of 20, 45 and 80 nm in diameters were discussed. The analytical figures for the determination of Au-labeled IgG using ICP-MS in conventional integral mode and single particle mode were compared in detail. Rabbit-anti-human IgG was used as a model analyte in the sandwich immunoassay. A detection limit (3 sigma) of 0.1 ng mL(-1) was obtained for rabbit-anti-human IgG after immunoreactions, with a linear range of 0.3-10 ng mL(-1) and a RSD of 8.1% (2.0 ng mL(-1)). Finally, the proposed method was successfully applied to spiked rabbit-anti-human IgG samples and rabbit-anti-human serum samples. The method resulted to be a highly sensitive ICP-MS based sandwich type immunoassay. PMID- 21035643 TI - A newly developed immunoassay method based on optical measurement for Protein A detection. AB - We describe the development of an immunoassay using an antibody-silver nanoparticle (Ab-AgNP) conjugate as a catalyst for the silver enhancement reaction. The immuno-reaction signals that were magnified by silver metal precipitation were quantified using a commercial flatbed scanner. Protein A from Staphylococcus aureus (S. aureus), a common clinical pathogenic bacterium, was used in this research. The ease of infection of S. aureus necessitates the development of a fast detection method. The framework of the method described in this paper is based on the sandwich immunoassay and contains a 1st antibody (immunoglobulin G, IgG), an antigen (Protein A), and a 2nd antibody-colloidal silver conjugate (IgG-AgNPs). The silver enhancement reaction, a signal amplification method in which silver ions are reduced to metallic silver, is used to magnify the immuno-reaction signal. The change in signal, as visualized in grayscale, can be easily observed and analyzed by our optical scanning detection system. The relationship between antigen concentration and grayscale value is discussed. The detectable concentration limit for the antigen was found to be 1 ng/mL with 10 MUg/mL of IgG and 300 MUM of the IgG-AgNP conjugate. This immunoassay method provides the advantages of low cost, easy operation, and short detection time. Moreover, it has potential applications in clinical diagnoses. PMID- 21035644 TI - Glucose concentration determination based on silica sol-gel encapsulated glucose oxidase optical biosensor arrays. AB - Optical biosensor arrays for rapidly determining the glucose concentrations in a large number of beverage and blood samples were developed by immobilizing glucose oxidase (GOD) on oxygen sensor layer. Glucose oxidase was first encapsulated in silica based gels through sol-gel approach and then immobilized on 96-well microarrays integrated with oxygen sensing film at the bottom. The oxygen sensing film was made of an organically modified silica film (ORMOSIL) doped with tris(4,7-diphenyl-1,10-phenanthroline) ruthenium dichloride (Ru(dpp)(3)Cl(2)). The oxidation reaction of glucose by glucose oxidase could be monitored through fluorescence intensity enhancement due to the oxygen consumption in the reaction. The luminescence changing rate evaluated by the dynamic transient method (DTM) was correlated with the glucose concentration with the wide linear range from 0.1 to 5.0mM (Y=13.28X-0.128, R=0.9968) and low detection limit (0.06 mM). The effects of pH and coexisting ions were systemically studied. The results showed that the optical biosensor arrays worked under a wide range of pH value, and normal interfering species such as Na(+), K(+), Cl(-), PO(4)(3-), and ascorbic acid did not cause apparent interference on the measurement. The activity of glucose oxidase was mostly retained even after 2-month storage, indicating their long-term stability. PMID- 21035645 TI - Simultaneous electrochemical determination of nitrate and nitrite in aqueous solution using Ag-doped zeolite-expanded graphite-epoxy electrode. AB - In this work a new electrochemical sensor based on an Ag-doped zeolite-expanded graphite-epoxy composite electrode (AgZEGE) was evaluated as a novel alternative for the simultaneous quantitative determination of nitrate and nitrite in aqueous solutions. Cyclic voltammetry was used to characterize the electrochemical behavior of the electrode in the presence of individual or mixtures of nitrate and nitrite anions in 0.1M Na(2)SO(4) supporting electrolyte. Linear dependences of current versus nitrate and nitrite concentrations were obtained for the concentration ranges of 1-10mM for nitrate and 0.1-1mM for nitrite using cyclic voltammetry (CV), chronoamperometry (CA), and multiple-pulsed amperometry (MPA) procedures. The comparative assessment of the electrochemical behavior of the individual anions and mixtures of anions on this modified electrode allowed determining the working conditions for the simultaneous detection of the nitrite and nitrate anions. Applying MPA allowed enhancement of the sensitivity for direct and indirect nitrate detection and also for nitrite detection. The proposed sensor was applied in tap water samples spiked with known nitrate and nitrite concentrations and the results were in agreement with those obtained by a comparative spectrophotometric method. This work demonstrates that using multiple pulse amperometry with the Ag-doped zeolite-expanded graphite-epoxy composite electrode provides a real opportunity for the simultaneous detection of nitrite and nitrate in aqueous solutions. PMID- 21035646 TI - Microemulsion electrokinetic chromatography: an application for the simultaneous determination of suspected fragrance allergens in rinse-off products. AB - A mixture of 18 neutral UV-active compounds with different characteristics of polarity was determined by capillary electrophoresis using a pseudostationary phase constituted by a microemulsion. The test analytes were volatile fragrance compounds, included in a list of 24 chemicals classified as suspected allergens according to Directive 2003/15/CE. The considered compounds were detected at 195 nm and p-anisaldehyde was chosen as internal standard. The background electrolyte consisted of a standard microemulsion made of 90.95% 10mM borax buffer, pH 9.2, 1.05% n-heptane, 8.00% SDS/n-butanol in 1:2 ratio, to which 40 mM methyl-beta cyclodextrin was added. Temperature and voltage were set at 20 degrees C and 25 kV, respectively. These experimental conditions allowed separation of the compounds to be obtained in about 20 min. The method was applied to real samples made up of rinse-off scented products. The results obtained using the standard microemulsion as pseudostationary phase showed its high resolution power, capable of effectively separating a complex mixture of analytes. Microemulsion electrokinetic chromatography was confirmed to have a great potential for different analytical challenges, holding up the possibility of using this technique as a good and complementary alternative to HPLC methods for routine analysis. PMID- 21035647 TI - Speciation of nickel by HPLC-UV/MS in pea nodules. AB - A new and sensitive methodology based on normal phase HPLC has been developed for the speciation of nickel in low-complexity plant extracts. The method combines a silica stationary phase column, a 9:1 (v/v) hexane:ethanol mixture as mobile phase, and the detection of nickel complexes by either UV or MS. The developed methodology was applied to the speciation of nickel complexes in the cytoplasm of pea root nodules. Results obtained indicate that nickel citrate and nickel malate accounts for 99% of nickel present in pea nodule cytoplasm fraction. The low detection limit of the method (<0.2 nM) enables nickel speciation in non hyperaccumulator plants. PMID- 21035648 TI - Versatile microanalytical system with porous polypropylene capillary membrane for calibration gas generation and trace gaseous pollutants sampling applied to the analysis of formaldehyde, formic acid, acetic acid and ammonia in outdoor air. AB - The analytical determination of atmospheric pollutants still presents challenges due to the low-level concentrations (frequently in the MUg m(-3) range) and their variations with sampling site and time. In this work, a capillary membrane diffusion scrubber (CMDS) was scaled down to match with capillary electrophoresis (CE), a quick separation technique that requires nothing more than some nanoliters of sample and, when combined with capacitively coupled contactless conductometric detection (C(4)D), is particularly favorable for ionic species that do not absorb in the UV-vis region, like the target analytes formaldehyde, formic acid, acetic acid and ammonium. The CMDS was coaxially assembled inside a PTFE tube and fed with acceptor phase (deionized water for species with a high Henry's constant such as formaldehyde and carboxylic acids, or acidic solution for ammonia sampling with equilibrium displacement to the non-volatile ammonium ion) at a low flow rate (8.3 nL s(-1)), while the sample was aspirated through the annular gap of the concentric tubes at 2.5 mL s(-1). A second unit, in all similar to the CMDS, was operated as a capillary membrane diffusion emitter (CMDE), generating a gas flow with know concentrations of ammonia for the evaluation of the CMDS. The fluids of the system were driven with inexpensive aquarium air pumps, and the collected samples were stored in vials cooled by a Peltier element. Complete protocols were developed for the analysis, in air, of NH(3), CH(3)COOH, HCOOH and, with a derivatization setup, CH(2)O, by associating the CMDS collection with the determination by CE-C(4)D. The ammonia concentrations obtained by electrophoresis were checked against the reference spectrophotometric method based on Berthelot's reaction. Sensitivity enhancements of this reference method were achieved by using a modified Berthelot reaction, solenoid micro-pumps for liquid propulsion and a long optical path cell based on a liquid core waveguide (LCW). All techniques and methods of this work are in line with the green analytical chemistry trends. PMID- 21035649 TI - Non-parametric linear regression of discrete Fourier transform convoluted chromatographic peak responses under non-ideal conditions of internal standard method. AB - This manuscript discusses the application of chemometrics to the handling of HPLC response data using the internal standard method (ISM). This was performed on a model mixture containing terbutaline sulphate, guaiphenesin, bromhexine HCl, sodium benzoate and propylparaben as an internal standard. Derivative treatment of chromatographic response data of analyte and internal standard was followed by convolution of the resulting derivative curves using 8-points sin x(i) polynomials (discrete Fourier functions). The response of each analyte signal, its corresponding derivative and convoluted derivative data were divided by that of the internal standard to obtain the corresponding ratio data. This was found beneficial in eliminating different types of interferences. It was successfully applied to handle some of the most common chromatographic problems and non-ideal conditions, namely: overlapping chromatographic peaks and very low analyte concentrations. For example, a significant change in the correlation coefficient of sodium benzoate, in case of overlapping peaks, went from 0.9975 to 0.9998 on applying normal conventional peak area and first derivative under Fourier functions methods, respectively. Also a significant improvement in the precision and accuracy for the determination of synthetic mixtures and dosage forms in non ideal cases was achieved. For example, in the case of overlapping peaks guaiphenesin mean recovery% and RSD% went from 91.57, 9.83 to 100.04, 0.78 on applying normal conventional peak area and first derivative under Fourier functions methods, respectively. This work also compares the application of Theil's method, a non-parametric regression method, in handling the response ratio data, with the least squares parametric regression method, which is considered the de facto standard method used for regression. Theil's method was found to be superior to the method of least squares as it assumes that errors could occur in both x- and y-directions and they might not be normally distributed. In addition, it could effectively circumvent any outlier data points. For the purpose of comparison, the results obtained using the above described internal standard method were compared with the external standard method for all types of linearity. PMID- 21035650 TI - Validated liquid chromatographic-fluorescence method for the quantitation of gemifloxacin in human plasma. AB - A highly selective, sensitive and rapid high performance liquid chromatographic method has been developed and validated to quantify gemifloxacin in human plasma. The gemifloxacin and internal standard (ciprofloxacin) were extracted by ultrafiltration technique followed by injection into chromatographic system. Chromatographic separation was achieved on a reversed phase C(18) column with a mobile phase of acetonitrile:0.1% trifluoroacetic acid (20:80, v/v) using isocratic elution (at flow rate 1 mL min(-1)). The analytes were detected at 269 and 393 nm for excitation and emission, respectively. The assay exhibited a linear range of 25-5000 ng mL(-1) for gemifloxacin in human plasma. The lower limit of detection was 10 ng mL(-1). The method was statistically validated for linearity, accuracy, precision and selectivity following FDA guidelines. The intra- and inter-assay coefficients of variation did not exceed 7.6% deviation of the nominal concentration. The recovery of gemifloxacin from plasma was greater than 97.0%. Stability of gemifloxacin in plasma was excellent with no evidence of degradation during sample processing (auto-sampler) and at least 3 months storage in a freezer at -70 degrees C. This validation method is applied for clinical study of the gemifloxacin in human volunteers. PMID- 21035651 TI - Quantification of free and total bisphenol A and bisphenol B in human urine by dispersive liquid-liquid microextraction (DLLME) and heart-cutting multidimensional gas chromatography-mass spectrometry (MD-GC/MS). AB - A novel method combining dispersive liquid-liquid microextraction (DLLME) and heart-cutting multidimensional gas chromatography coupled to mass spectrometry was developed for the determination of free and total bisphenol A (BPA) and bisphenol B (BPB) in human urine samples. The DLLME procedure combines extraction, derivatization and concentration of the analytes into one step. Several important variables influencing the extraction efficiency and selectivity such as nature and volume of extractive and dispersive solvents as well as the amount of acetylating reagent were investigated. The temperature and time to hydrolyze BPA and BPB conjugates with a beta-glucuronidase and sulfatase enzyme preparation were also studied. Under the optimized conditions good efficiency extraction (71-93%) and acceptable total DLLME yields (56-77%) were obtained for both analytes. Matrix-matched calibration curves were linear with correlation coefficients higher than 0.996 in the range level 0.1-5 MUg/l, and the relative standard deviations (%RSD) were lower than 20% (n=6). The limits of detection were 0.03 and 0.05 MUg/l for BPA and BPB, respectively. The applicability of the proposed method for determining urinary free and total BPA and BPB was assessed by analyzing the human urine of a group of 20 volunteers. Free BPA was detected in 45% of the sample whereas total BPA was detected in 85% of the samples at concentrations ranging between 0.39 and 4.99 MUg/l. BPB was detected in conjugated form in two samples. PMID- 21035652 TI - A simple and fast method for chlorsulfuron and metsulfuron methyl determination in water samples using multiwalled carbon nanotubes (MWCNTs) and capillary electrophoresis. AB - A new method to determine metsulfuron methyl (MSM) and chlorsulfuron (CS) in different water samples was developed. It consists in a solid phase extraction (SPE) procedure using multiwalled carbon nanotubes (MWCNTs) as sorbent material in combination with capillary zone electrophoretic determination. To carry out the pre-concentration step, a simple flow injection system was developed and optimized. Thus, 250 MUL of aqueous solution containing methanol 50% (v/v) and acetonitrile 2% (v/v) as eluent, 10 mL of sample and a flow rate of 1.15 mL min( 1) were selected. The CE variables also were optimized. A rapid determination and good resolution of two herbicides were obtained within 9 min using a simple electrophoretic buffer (50 mmol L(-1) sodium tetraborate with 3% of methanol, pH=9.0). Under the optimum conditions, the calibration curves were linear between 0.5 and 6 MUg L(-1) for MSM and CS with R(2)=0.995 and 0.997, respectively. The repeatability of the proposed method, expressed as relative standard deviation (RSD), varied between 4.1% and 5.4% (n=10) and the detection limits for MSM and CS were 0.40 and 0.36 MUg L(-1), respectively. Good results were achieved when the proposed method was applied to spiked real water samples. The recoveries percentages of the two analytes were over the range 86-108%. PMID- 21035653 TI - A batch modelling approach to monitor a freeze-drying process using in-line Raman spectroscopy. AB - Freeze-drying or lyophilisation is a batch wise industrial process used to remove water from solutions, hence stabilizing the solutes for distribution and storage. The objective of the present work was to outline a batch modelling approach to monitor a freeze-drying process in-line and in real-time using Raman spectroscopy. A 5% (w/v) D-mannitol solution was freeze-dried in this study as model. The monitoring of a freeze-drying process using Raman spectroscopy allows following the product behaviour and some process evolution aspects by detecting the changes of the solutes and solvent occurring during the process. Herewith, real-time solid-state characterization of the final product is also possible. The timely spectroscopic measurements allowed the differentiation between batches operated in normal process conditions and batches having deviations from the normal trajectory. Two strategies were employed to develop batch models: partial least squares (PLS) using the unfolded data and parallel factor analysis (PARAFAC). It was shown that both strategies were able to developed batch models using in-line Raman spectroscopy, allowing to monitor the evolution in real-time of new batches. However, the computational effort required to develop the PLS model and to evaluate new batches using this model is significant lower compared to the PARAFAC model. Moreover, PLS scores in the time mode can be computed for new batches, while using PARAFAC only the batch mode scores can be determined for new batches. PMID- 21035654 TI - Ultrasensitive mercury(II) ion detection by europium(III)-doped cadmium sulfide composite nanoparticles. AB - With the biomolecule glutathione (GSH) as a capping ligand, Eu(3+)-doped cadmium sulfide composite nanoparticles were successfully synthesized through a straightforward one-pot process. An efficient fluorescence energy transfer system with CdS nanoparticles as energy donor and Eu(3+) ions as energy accepter was developed. As a result of specific interaction, the fluorescence intensity of Eu(3+)-doped CdS nanoparticles is obviously reduced in the presence of Hg(2+). Moreover, the long fluorescent lifetime and large Stoke's shift of europium complex permit sensitive fluorescence detection. Under the optimal conditions, the fluorescence intensity of Eu(3+) at 614 nm decreased linearly with the concentration of Hg(2+) ranging from 10 nmol L(-1) to 1500 nmol L(-1), the limit of detection for Hg(2+) was 0.25 nmol L(-1). In addition to high stability and reproducibility, the composite nanoparticles show a unique selectivity towards Hg(2+) ion with respect to common coexisting cations. Moreover, the developed method was applied to the detection of trace Hg(2+) in aqueous solutions. The probable mechanism of reaction between Eu(3+)-doped CdS composite nanoparticles and Hg(2+) was also discussed. PMID- 21035655 TI - A pH responsive electrochemical switch sensor based on Fe(notpH3) [notpH6 = 1,4,7 triazacyclononane-1,4,7-triyl-tris(methylene-phosphonic acid)]. AB - The electrochemistry of a macrocyclic metal complex Fe(notpH(3)) [notpH(6)=1,4,7 triazacyclononane-1,4,7-triyl-tris(methylene-phosphonic acid)] reveals that the protonation/deprotonation of the non-coordinated P-OH groups in Fe(notpH(3)) affects its formal potential value (E(0)') considerably. Plotting E(0)' as function of solution pH gives a straight line with a slope of -585 mV pH(-1) in the pH range of 3.4-4.0, which is about ten times larger than the theoretical value of -58 mV pH(-1) for a reversible proton-coupled single-electron transfer at 20 degrees C. A sensitive pH responsive electrochemical switch sensor is thus developed based on Fe(notpH(3)) which shows an "on/off" switching at pH ~ 4.0. PMID- 21035656 TI - A comparison of edge- and basal-plane pyrolytic graphite electrodes towards the sensitive determination of hydrocortisone. AB - Electrochemical sensor employing edge-plane pyrolytic graphite electrode (EPPGE) for the sensitive detection of hydrocortisone (HC) is delineated for the first time. The electrochemical properties are investigated exercising the cyclic voltammetry and square-wave voltammetry (SWV). When equating with the bare basal plane pyrolytic graphite electrode (BPPGE), the EPPGE gave better response towards the detection of HC both in terms of sensitivity and detection limit. The voltammetric results indicated that EPPGE remarkably enhances the reduction of HC which leads to considerable amelioration of peak current with shift of peak potential to less negative values. The difference in the surface morphology of two electrodes has been studied. Also, the EPPGE delivered an analytical performance for HC with a sensitivity of 45 nA nM(-1) and limit of detection of 88 nM in the concentration range 100-2000 nM. The method has been utilized for the determination of HC in pharmaceuticals and real samples. The electroanalytical method using EPPGE is the most sensitive method for determination of HC with lowest limit of detection to date. The major metabolites present in blood plasma did not intervene with the present investigation as they did not exhibit reduction peak in the experimental range used. A comparison of results with high performance liquid chromatography (HPLC) signalizes a good agreement. PMID- 21035657 TI - Lysozyme-imprinted polymer synthesized using UV free-radical polymerization. AB - Molecular imprinting is a method to fabricate a polymeric material (molecularly imprinted polymer or MIP) capable of selectively recognizing template molecules. Molecular imprinting of small molecules has been studied widely. Less common, however, is the imprinting of biological macromolecules, including proteins, among which lysozyme is an important molecule in the food, pharmaceutical, and diagnostic sciences. In this study, lysozyme MIP was fabricated in two steps. First, lysozyme, PEG600DMA, and methacrylic acid were used as the template molecule, cross-linking monomer, and the functional monomer, respectively, in a UV free-radical polymerization process to synthesize a polymeric gel. Second, lysozyme was removed by enzymatic digestion. Non-imprinted polymer (NIP) was synthesized without lysozyme addition. To evaluate the preferential binding capability of MIP, lysozyme, RNase A, or a 50:50 mixture of lysozyme and RNase A was added to MIP and NIP and then released by digestion. It was found that when more lysozyme was added to the reaction mixture, the quantity of protein released from the polymer increased, reflecting more potential binding sites. Tests of MIP with a competitive binding mixture of lysozyme and RNase A showed the MIP preferentially bound a greater amount of lysozyme, up to 20 times more than RNase A. NIP bound only small amounts of both proteins and did not show a preference for binding either lysozyme or RNase A. These results demonstrate that lysozyme was successfully imprinted into the MIP by UV free-radical polymerization, and the fabricated MIP was able to preferentially bind its template protein. PMID- 21035658 TI - Direct electrochemistry of hemoglobin immobilized in CuO nanowire bundles. AB - It is one of main challenges to find the suitable materials to enhance the direct electron transfer between the electrode and redox protein for direct electrochemistry field. Nano-structured metal oxides have attracted considerable interest because of unique properties, well biocompatibility, and good stability. In this paper, the copper oxide nanowire bundles (CuO NWBs) were prepared via a template route, and the bioelectrochemical performances of hemoglobin (Hb) on the CuO NWBs modified glass carbon electrodes (denoted as Hb-CuO NWBs/GC) were studied. TEM and XRD were used to characterize the morphology and structure of the as synthesized CuO NWBs. Fourier transform-infrared spectroscopy (FT-IR) proved that Hb in the CuO NWBs matrix could retain its native secondary structure. A pair of well-defined and quasi-reversible redox peaks at approximately -0.325 V (vs. Ag/AgCl saturated KCl) were shown in the cyclic voltammogram curve for the Hb-CuO NWBs/GC electrode, which indicated the direct electrochemical behavior. The Hb-CuO NWBs/GC electrode also displayed a good electrocatalytic activity toward the reduction of hydrogen peroxide. These results indicate that the CuO NWBs are good substrates for immobilization of biomolecules and might be promising in the fields of (bio) electrochemical analysis. PMID- 21035659 TI - The use of a gold disc microelectrode for the determination of copper in human sweat. AB - A novel approach of using a gold disc microelectrode to analyze sweat samples for copper ions by anodic square wave stripping voltammetry (SW stripping voltammetry) is described. Sweat was collected from the lower back of four subjects after physical exercise and the sample volume required for the determinations was 100 MUL. Under the optimized conditions, the calibration plot was linear over the range 1-100 MUmol L(-1) Cu(II) with a limit of detection of 0.25 MUmol L(-1). The precision was evaluated by carrying out five replicate measurements in a 1 MUmol L(-1) Cu(II) solution and the standard deviation was found to be 1.5%. Measurements were performed by inserting the microelectrode into sweat drops and Cu(II) concentrations in the analyzed samples ranged from 0.9 to 28 MUmol L(-1). Values obtained by the proposed voltammetric method agreed well with those found using graphite furnace atomic absorption spectroscopy (GFAAS). PMID- 21035660 TI - Analysis of sediment-associated insecticides using ultrasound assisted microwave extraction and gas chromatography-mass spectrometry. AB - An ultrasound assisted microwave extraction (UAME) method was developed to simultaneously extract five organophosphate (OP) and eight pyrethroid insecticides from sediment. The optimized UAME conditions were to use 100ml of a mixture of hexane and acetone (1:1, v/v) solution as the extraction solvents, and extraction time, microwave and ultrasonic power settings of 6 min, 100 W and 50 W, respectively. Extracts were cleaned using solid phase extraction and analyzed by gas chromatography-mass spectrometry in negative chemical ionization mode and quantification was based on matrix-matched standard solutions along with internal standard calibration. At the spiked concentrations of 1, 5 and 20 ng/g dry weight (dw), recoveries of OPs were 77.6-122%, 65.2-128% and 75.6-141% with relative standard deviations (RSDs) of 10.6-18.1%, 3.1-12.5% and 8.0-35.3%, respectively, while recoveries of pyrethroids were 78.0-101%, 76.4-104% and 71.0-99.5% with RSDs of 10.3-23.5%, 4.7-17.6% and 8.8-18.7%, respectively. Method detection limits ranged from 0.31 to 0.45 ng/g dw for the OP insecticides and from 0.27 to 0.70 ng/g dw for the pyrethroid insecticides. The newly developed UAME method was validated by comparing it to Soxhlet and sonication extraction methods. Better recoveries were achieved for most OPs by the novel UAME method, whereas there was no significant difference in recoveries for most of the pyrethroids. Finally, the UAME method was used to quantify the target insecticides in field-contaminated sediment samples which were collected in Guangzhou, China. PMID- 21035661 TI - High resolution detection of high mass proteins up to 80,000 Da via multifunctional CdS quantum dots in laser desorption/ionization mass spectrometry. AB - CdS quantum dots (~ 5 nm) are used as multifunctional nanoprobes as an effective matrix for large proteins, peptides and as affinity probes for the enrichment of tryptic digest proteins (lysozyme, myoglobin and cytochrome c) in laser desorption/ionization time-of-flight mass spectrometry (LDI-TOF MS). The use of CdS quantum dots (CdS QDs) as the matrix allows acquisition of high resolution LDI mass spectra for large proteins (5000-80,000 Da). The enhancement of mass resolution is especially notable for large proteins such as BSA, HSA and transferrin (34-49 times) when compared with those obtained by using SA as the matrix. This technique demonstrates the potentiality of LDI-TOF-MS as an appropriate analytical tool for the analysis of high-molecular-weight biomolecules with high mass resolution. In addition, CdS QDs are also used as matrices for background-free detection of small biomolecules (peptides) and as affinity probes for the enrichment of tryptic digest proteins in LDI-TOF-MS. PMID- 21035662 TI - Time-resolved fluorescence aptamer-based sandwich assay for thrombin detection. AB - In the present study, the authors report a novel sensitive method for the detection of thrombin using time-resolved fluorescence sensing platform based on two different thrombin aptamers. The thrombin 15-mer aptamer as a capture probe was covalently attached to the surface of glass slide, and the thrombin 29-mer aptamer was fluorescently labeled as a detection probe. A bifunctional europium complex was used as the fluorescent label. The introduction of thrombin triggers the two different thrombin aptamers and thrombin to form a sandwich structure. The fluorescence intensity is proportional to the thrombin concentration. The present sensing system could provide both a wide linear dynamic range and a low detection limit. The proposed sensing system also presented satisfactory specificity and selectivity. Results showed that thrombin was retained at the aptamer-modified glass surface while nonspecific proteins were removed by rinsing with buffer solution. This approach successfully showed the suitability of aptamers as low molecular weight receptors on glass slides for sensitive and specific protein detection. PMID- 21035663 TI - Enhanced sensing of ascorbic acid, dopamine and serotonin at solid carbon paste electrode with a nonionic polymer film. AB - A nonionic poly(2-amino-5-mercapto-thiadiazole) film was electrodeposited on a solid carbon paste electrode via a potential scanning procedure, and used for amperometric sensing of ascorbic acid (AA), dopamine (DA) and serotonin (ST). The highly electrocatalytic activity of the sensor to the three analytes was demonstrated from the sensitive and well separated voltammetric signals. The polymer film did not show significant accumulation effect on all the three species, reducing the fouling and deactivation of the electrode surface as well as the mutual interference among the analytes. The sensor achieved amperometric sensitivities of 1.92 nA (nmol L(-1))(-1)cm(-2) to AA in the linear range of 0.025-1.95 MUmol L(-1), 3.76 nA (nmol L(-1))(-1)cm(-2) to DA and 7.00 nA (nmol L( 1))(-1)cm(-2) to ST both in the linear range of 0.02-1.56 MUmol L(-1). The lowest detection limits were found to be 1.5, 0.7 and 0.4 nmol L(-1) for AA, DA and ST, respectively. This sensor was successfully employed for the successive determination of AA, DA and ST in pharmaceutical samples. The good antifouling property and reproducibility of the proposed sensor can be attributed to the nonionic polymer film without electrostatic attraction to the ionized species in the solutions. PMID- 21035664 TI - Electrodeposited silver nanodendrites electrode with strongly enhanced electrocatalytic activity. AB - Highly uniform dendritic silver nanostructures as a new electrode material, have been synthesized by electrodeposition on the glassy carbon (GC) electrode with assistance of polyethylene glycol 400 (PEG-400) as a soft template, to achieve a superior electrocatalyst with enhanced detection sensitivity in electroanalysis compared to conventional bulk Ag electrodes. The effects of the growth conditions such as concentrations of the reagents and applied potentials on the morphology and structure of as-prepared tree-like nanostructures have also been investigated by scanning electron microscopy (SEM), atomic force microscopy (AFM) and X-ray diffraction (XRD). In the silver nanodendrites (AgNDs), the diameter of the trunk is around 100-200 nm with length up to 10-40 MUm, and the length of its branches can reach 10 MUm. In addition, the electrocatalytic behavior of this modified electrode was exploited as a sensitive detection system for the reduction of RDX high explosive, hydrogen peroxide and hexacyanoferrate (HCF) by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) techniques. Also, the obtained results were compared to multiwalled carbon nanotubes (MWCNTs) and bulk silver electrodes. These studies show that the nanodendritic silvers significantly increase the electron-transfer rate of the electrochemical reactions by as much as 1-2 orders of magnitude. PMID- 21035665 TI - Electrochemical sensing platform based on covalent immobilization of thionine onto gold electrode surface via diazotization-coupling reaction. AB - A novel electrochemical sensing platform by modification of electroactive thionine (Th) onto gold electrode surface was constructed, which was realized by diazotization of 4-aminothiophenol (ATP) self-assembled monolayer, followed by coupling of Th with the diazonium group to form a covalent diazo bond. A pair of well-defined redox peaks of Th was observed in the cyclic voltammetric measurement. The resulting diazo-ATP monolayer displayed superior electrical conductivity, which contributed to the sensitive detection of hydrogen peroxide (H(2)O(2)). The immobilized Th also showed a remarkable stability, which may benefit from the pi-pi stacking force and the covalent diazo bond between diazo ATP and Th molecules. Under the optimized experimental conditions, the current fabricated non-enzyme and reagentless sensor could show a rapid response to H(2)O(2) within 3s and a linear calibration plot ranged from 1.0 * 10(-6) to 6.38 * 10(-3)M with a detection limit of 6.7 * 10(-7)M. The current fabrication strategy of electroactive interface is expected to be used as a versatile route for the immobilization of more electroactive molecules and offer more opportunities for the applications in electrochemical sensor, biosensor, electrocatalysis, etc. PMID- 21035666 TI - Highly sensitive fluorescence quantification of picloram using immunorecognition liposome. AB - Picloram is a widely used chlorinated herbicide, which is quite persistent and mobile in soil and water with adverse health and environmental risks. A simple and efficient method with high sensitivity and good selectivity was developed in this work to analyze picloram. The aldehyde group functionalized quartz glass plate was used to catch picloram by Schiff base reaction, and reacted with the liposomes-labeled antibody. The fluorescein isothiocyanate (FITC) solution was encapsulated in the liposomes. After being released from the liposomes, the fluorescence of FITC was measured by a fluorimeter. It was found that the fluorescence intensity is linearly correlated to the logarithm of picloram concentration, ranging from 1.0 * 10(-4) to 100 ng mL(-1), with a detection limit of 1.0 * 10(-5) ng mL(-1). Picloram concentration in real wastewater samples were accurately measured by the proposed method and HPLC, the results of the two methods were approximately the same. The proposed method showed high sensitivity and good selectivity, and could be an efficient tool for picloram quantitative analysis. PMID- 21035667 TI - Analysis of chemical signals in red fire ants by gas chromatography and pattern recognition techniques. AB - Gas chromatographic (GC) profiles of cuticular hydrocarbon extracts obtained from individual and pooled ant samples were analyzed using pattern recognition techniques. Clustering according to the biological variables of social caste and colony were observed. Pooling individual extracts enhanced the recognition of patterns in the GC profile data characteristic of colony. Evidently, the contribution of the ant's individual pattern to the overall hydrocarbon profile pattern can obscure information about colony in the GC traces of cuticular hydrocarbon extracts obtained from red fire ants. Re-analysis of temporal caste and time period data on the cuticular hydrocarbon patterns demonstrates that sampling time and social caste must be taken into account to avoid unnecessary variability and possible confounding. This and the fact that foragers could not be separated from reserves and brood-tenders in all five laboratory colonies studied suggests that cuticular hydrocarbons as a class of sociochemicals cannot model every facet of nestmate recognition in Solenopsis invicta which in turn suggests a potential role for other compounds in the discrimination of alien conspecifics from nestmates. PMID- 21035668 TI - Application of multivariate image analysis in QSPR study of 13C chemical shifts of naphthalene derivatives: a comparative study. AB - A new implemented QSPR method, whose descriptors achieved from bidimensional images, was applied for predicting (13)C NMR chemical shifts of 25 mono substituted naphthalenes. The resulted descriptors were subjected to principal component analysis (PCA) and the most significant principal components (PCs) were extracted. MIA-QSPR (multivariate image analysis applied to quantitative structure-property relationship) modeling was done by means of principal component regression (PCR) and principal component-artificial neural network (PC ANN) methods. Eigen value ranking (EV) and correlation ranking (CR) were used here to select the most relevant set of PCs as inputs for PCR and PC-ANN modeling methods. The results supported that the correlation ranking-principal component artificial neural network (CR-PC-ANN) model could predict the (13)C NMR chemical shifts of all 10 carbon atoms in mono substituted naphthalenes with R(2) >= 0.922 for training set, R(2) >= 0.963 for validation set and R(2) >= 0.936 for the test set. Comparison of the results with other existing factor selection method revealed that less accurate results were obtained by the eigen value ranking procedure. PMID- 21035669 TI - Direct determination of benzo[a]pyrene in water samples by a gold nanoparticle based solid phase extraction method and laser-excited time-resolved Shpol'skii spectrometry. AB - The strong affinity between polycyclic aromatic hydrocarbons (PAH) and the surface of gold colloids is investigated to device an extraction method for water samples. Within the 20-100 nm particle diameter range, the 20 nm gold nanoparticles showed the best extraction efficiencies for all the studied analytes. The new approach is combined to laser-excited time-resolved Shpol'skii spectrometry for the direct analysis of benzo[a]pyrene in drinking water samples. For a 500 MUL sample volume, the analytical figures of merit demonstrate precise and accurate analysis at the parts-per-trillion level. The extraction efficiencies are statistically equivalent to 100% with relative standard deviations lower than 2%. The average recoveries were varied from 87.5% to 96.5% for different concentration of analytes. The simplicity of the experimental procedure, the low analysis cost, and the excellent analytical figures of merit demonstrate the potential of this approach for routine analysis of drinking water samples. PMID- 21035670 TI - Niobium oxide dispersed on a carbon-ceramic matrix, SiO2/C/Nb2O5, used as an electrochemical ascorbic acid sensor. AB - A film of niobium oxide was immobilized on a SiO(2)/C carbon-ceramic matrix (specific surface area 270 m(2)g(-1)) and characterized by N(2) adsorption desorption isotherms, scanning electron microscopy, X-ray photoelectron spectroscopy and atomic force microscopy. This new carbon-ceramic material, SiO(2)/C/Nb(2)O(5), was used for construction of electrodes, and it shows ability to improve the electron-transfer between the electrode surface and ascorbic acid. The electrocatalytic oxidation of ascorbic acid was made by differential pulse and cyclic voltammetry techniques, making it potentially useful for developing a new ascorbic acid sensor. PMID- 21035671 TI - An amperometric biosensor based on peroxidases from Brassica napus for the determination of the total polyphenolic content in wine and tea samples. AB - An amperometric biosensor based on peroxidases from Brassica napus hairy roots (PBHR) used to determine the total polyphenolic content in wine and tea samples is proposed by the first time. The method employs carbon paste (CP) electrodes filled up with PBHR, ferrocene (Fc), and multi-walled carbon nanotubes embedded in a mineral oil (MWCNT+MO) at a given composition (PBHR-Fc-MWCNT+MO). The biosensor was covered externally with a dialysis membrane, which was fixed at the electrode body side part with a Teflon laboratory film and an O-ring. Calibration curves obtained from steady-state currents as a function of the concentration of a polyphenolic standard reference compound such as t-resveratrol (t-Res) or caffeic acid (CA) were then used to estimate the total polyphenolic content in real samples. The reproducibility and the repeatability were of 7.0% and 4.1% for t-Res (8.4% and 5.2% for CA), respectively, showing a good biosensor performance. The calibration curves were linear in a concentration range from 0.05 to 52 mg L( 1) and 0.06 to 69 mg L(-1) for t-Res and CA, respectively. The lowest polyphenolic compound concentration values measured experimentally for a signal to noise ratio of 3:1 were 0.023 mg L(-1) and 0.020 mg L(-1) for t-Res and CA, respectively. PMID- 21035672 TI - Laser induced fluorescence and photochemical derivatization for trace determination of camptothecin. AB - Laser-excited fluorescence was used for the selective determination of camptothecin in samples containing anti-cancer camptothecin-analogs (irinotecan and topotecan). The selectivity of the method was based on the UV photochemical derivatization in basic solution which increased the analyte fluorescence (337/450 nm) and eliminated fluorescence from the two campthotecin-analogs. The influence of UV exposure time and sodium hydroxide concentration was studied using an experimental design. Limit of detection was 4 * 10(-10) mol L(-1) with linear fluorescence response up to 1 * 10(-6)mol L(-1). Average recoveries of camptothecin (added to the samples to simulate a contamination) were 92 +/- 4 and 94 +/- 6% (n=3) respectively in irinotecan and topotecan based pharmaceuticals. PMID- 21035673 TI - GC/MS-based metabolomics reveals fatty acid biosynthesis and cholesterol metabolism in cell lines infected with influenza A virus. AB - Metabolomics is the downstream of systems biology and has drawn significant interest for studying the metabolic networks from cells to organisms. To profile the metabolites in two different cell lines (A549 and AGS) infected with influenza A virus, gas chromatography coupled with mass spectrometry (GC/MS) was employed. Some differentiating metabolites in the cell lines were tentatively identified using reference library, interpreted and visualized by applying principal components analysis (PCA) and cluster heat map. Consequently, metabolic flux profiling allowed the differentiation of fatty acid biosynthesis and cholesterol metabolism during viral replication in the cell lines. The change in fatty acid turnover was also observed. Metabolomics investigation also revealed the different responses between A549 and AGS cell lines to the virus infection. From the pattern recognition results, AGS cell line might be more susceptible to influenza A virus. Regarding the fact that AGS is a poorly differentiated gastric adenocarcinoma cell line whereas A549 is a relatively differentiated lung tumor one, it is speculated that viral replication might be associated with the cell differentiations. PMID- 21035675 TI - Monitoring the redox cycle of low-molecular peptides using a modified target plate in MALDI-MS. AB - A new method is being proposed for preparing MALDI target plates with a hydrophobic polymer coating and hydrophilic anchors. The particles of the MALDI matrix were pre-mixed with a poly[4,5-difluoro-2,2-bis(trifluoromethyl)-1,3 dioxole-co-tetrafluoroethylene] solution prior to their placement on a mass spectrometric sample support. This technique led to the formation of matrix microspots with a diameter of less than 1mm inside the polymer. The polymer and matrix concentration as well as the amount of suspension placed on the target plate influenced the size and quality of microspots to a great extent. The sensitivity of the mass-spectrometric analysis was confirmed by obtaining the mass spectra of fmole concentrations of an apomyoglobin tryptic digest. The potential proteomic application of this type of MALDI surface preparation was demonstrated by performing the redox cycle using glutathione and its analogue. All reactions were carried out directly on a MALDI plate, which accommodates low volumes of reagents and prevents sample loss. PMID- 21035674 TI - A novel amperometric biosensor based on single walled carbon nanotubes with acetylcholine esterase for the detection of carbaryl pesticide in water. AB - Amperometric biosensor is fabricated for the detection of carbaryl based on single walled carbon nanotubes (SWCNTs) and acetylcholine esterase (AchE). The dispersion of SWCNTs in positively charged polyelectrolyte, poly(diallyldimethylammonium chloride) (PDDA), possibly takes place due to weak supramolecular interaction between them, which then binds electrostatically to the negatively charged AchE at pH 7.4 using layer-by-layer (LbL) self-assembly technique. The optical intensity of UV/vis spectra increased with the number of layers, indicating the build up of a multilayer coating on the electrode. The activity of acetylcholine esterase on modified electrode of 3mm in diameter was found to be 0.2U. The biosensor showed good sensitivity and stability towards the monitoring of carbaryl pesticides in water with the detection limit of 10(-12)gL( 1) and recovery of 99.8 +/- 2.7% to 10(-10)gL(-1). This protocol can be used for the immobilization of other enzymes to fabricate a range of biosensors. PMID- 21035676 TI - Correlation between different clean-up methods and analytical techniques performances to detect Ochratoxin A in wine. AB - Three different clean-up methods and two analytical techniques were compared to determine Ochratoxin A (OTA) in wines. The first clean-up used a MycoSep column, the second an immunoaffinity column (IAC) and the third consisted in a liquid liquid extraction (LLE) using dichloromethane in acid conditions. Meanwhile, two different OTA determination techniques were also evaluated: a HPLC analysis using a fluorescence detector and an enzyme-linked immunosorbent assays (ELISA) method. Correlations between clean-up methods and analytical techniques to determine OTA in wine were made evaluating linearity, accuracy and precision. Both the two first clean-up methods (solid-phase extraction, SPE) showed a good linear fit (r(2)=about 0.9999), followed by LLE. The use of immunoaffinity columns showed the best recoveries, even if also the SPE with MycoSep showed good recoveries while the LLE recoveries were the worst ones. The HPLC analysis showed good precision and accuracy, while ELISA method, even with a sufficient linearity, generally underestimated OTA content in wines. PMID- 21035677 TI - Preparation and application of rifamycin-capped (3-(2-O-beta-cyclodextrin)-2 hydroxypropoxy)-propylsilyl-appended silica particles as chiral stationary phase for high-performance liquid chromatography. AB - Rifamycin-capped (3-(2-O-beta-cyclodextrin)-2-hydroxypropoxy)-propylsilyl appended silica particles (RCD-HPS), a new type of substituted beta-cyclodextrin bonded chiral stationary phase (CSP) for high-performance liquid chromatography (HPLC), have been synthesized by the treatment of bromoacetate-substituted-(3-(2 O-beta-cyclodextrin)-2-hydroxypropoxy)-propylsilyl-appended silica particles (BACD-HPS) with rifamycin SV in anhydrous acetonitrile. The stationary phase is characterized by means of elemental analysis and Fourier-transform infrared spectroscopy. This new CSP has a chiral selector with two recognition sites: rifamycin and beta-cyclodextrin (beta-CD). The chromatographic behavior of RCD HPS was studied with several disubstituted benzenes and some chiral drug compounds under reversed-phase HPLC mobile phase conditions. The results show that RCD-HPS has excellent selectivity for the separation of aromatic positional isomers and enantiomers of chiral compounds due to the cooperative functioning of rifamycin and beta-CD. PMID- 21035678 TI - Monitoring the quality of frying oils using a nanolayer coated optical fiber refractometer. AB - The analysis of the quality of food oils is of paramount importance, because the degradation of oils can lead to formation of harmful substances to the human organism. With the increase of the degradation of oils an increase of its refractive index occurs. The objective of this work is to develop and to characterize optical fiber refractometers sensitive to variations of refractive index of food oil samples. The optical fiber refractometers thanks to the intrinsic characteristics make them suitable for monitoring the quality of frying oils. They possess the advantages to require small volumes of sample for analysis, do not contaminate the sample, and supply the response in real time. In this work a long period grating (LPG) as refractometer is used because of their sensitivity to refractive index of the external media: degraded and not degraded frying oil samples. The oil samples had been characterized by the analysis of total polar components. The refractive index of oil is above 1.47, this region the LPG does not show enough sensitivity, a nanolayer of an organic material was coated onto the fiber. Using the Langmuir-Blodgett technique the response of LPG is modified according to the refractive index and thickness of the film. The deposition of the film modifies the rates effective modes of cladding, thus improving the response of the changes in the refractive index of the external media higher than that the refractive index of the cladding (n=1.457). PMID- 21035679 TI - Determination of beer aroma compounds using headspace solid-phase microcolumn extraction. AB - A rapid sampling technique for the analysis of beer aroma compounds is described. The headspace (10 ml) is passed through the microcolumn filled with 5mg of Tenax TA and thermally desorbed in a modified GC inlet (modification is described). Eight compounds (from acetaldehyde to 2-phenylethanol) in four beer samples were analyzed. The correlation coefficients (r(2)), repeatability (RSD) and limits of detection (LOD) were 0.9973-0.9994, 2.1-6.9% and 0.00002-0.13 mg/l, respectively. The methodology can be useful for routine beer sample analysis. PMID- 21035680 TI - The study of calcium in living cells. Preface. PMID- 21035681 TI - A practical guide to the preparation of Ca(2+) buffers. AB - Calcium (Ca(2+)) is a critical regulator of an immense array of biological processes, and the intracellular [Ca(2+)] that regulates these processes is ~ 10,000 lower than the extracellular [Ca(2+)]. To study and understand these myriad Ca(2+)-dependent functions requires control and measurement of [Ca(2+)] in the nano- to micromolar range (where contaminating Ca(2+) is a significant problem). As with pH, it is often essential to use Ca(2+) buffers to control free [Ca(2+)] at the desired biologically relevant concentrations. Fortunately, there are numerous available Ca(2+) buffers with different affinities that make this practical. However, there are numerous caveats with respect to making these solutions appropriately with known Ca(2+) buffers. These include pH dependence, selectivity for Ca(2+) (e.g., vs. Mg(2+)), ionic strength and temperature dependence, and complex multiple equilibria that occur in physiologically relevant solutions. Here we discuss some basic principles of Ca(2+) buffering with respect to some of these caveats and provide practical tools (including freely downloadable computer programs) to help in the making and calibration of Ca(2+)-buffered solutions for a wide array of biological applications. PMID- 21035682 TI - Photorelease techniques for raising or lowering intracellular Ca(2+). AB - The quantitative manipulation of intracellular calcium concentration ([Ca(2+)](i)) is a valuable instrument in the modern cell biologists' toolbox for unraveling the many cell processes controlled by calcium. I summarize here the major classes of photosensitive calcium chelators used to elevate or reduce [Ca(2+)](i), with an emphasis on their physicochemical properties and methods of calculating magnitudes and kinetics of effects on [Ca(2+)](i) of flashes and steady light, in order to encourage the choice of the best substance for particular applications. The selection and calibration of appropriate light sources, and procedures for introducing the chelators into cells, spatially restricting [Ca(2+)](i) changes, and measuring the profiles of [Ca(2+)](i) changes imposed by photolysis, are also described. The final section describes a selection of biological applications. PMID- 21035683 TI - Making and using calcium-selective mini- and microelectrodes. AB - Detection and measurement of intracellular calcium concentration ([Ca(2+)](i)) have relied on various methods, the popularity of which depends on their ease of use and applicability to different cell types. Historically, Ca(2+)-selective electrodes have been used concomitantly with absorption indicators such as arsenazo-III, but their interest has been eclipsed by the introduction of a large number of fluorescent calcium probes with calcium sensitivities varying from the nanomolar to the micromolar range such as fura-2, indo-1, fluo-4, and many others. In this chapter, we emphasize the utility of Ca(2+)-selective electrodes and show that their use is complementary to use of fluorescent indicators; indeed, each method has advantages and disadvantages. We first describe the preparation and application of Ca(2+)-selective minielectrodes based on the Ca(2+) ligand ETH 129 (Schefer et al., 1986) that have a larger dynamic range and faster response time than most commercially available calcium electrodes. The second part of the chapter is dedicated to ETH 129-based Ca(2+)-selective microelectrodes (MEs), and their application in the determination of [Ca(2+)](i) in cardiac cells. Since numerous reviews and books have been dedicated to the theoretical aspects of ion-selective ME principles and technology, this chapter is not intended for investigators who have no experience with MEs. PMID- 21035684 TI - Construction, theory, and practical considerations for using self-referencing of Ca(2+)-selective microelectrodes for monitoring extracellular Ca(2+) gradients. AB - Ca(2+) signaling in the extra- and intracellular domains is linked to Ca(2+) transport across the plasma membrane. Noninvasive monitoring of these resulting extracellular Ca(2+) gradients with self-referencing of Ca(2+)-selective microelectrodes is used for studying Ca(2+) signaling across Kingdoms. The quantitated Ca(2+) flux enables comparison with changes to intracellular [Ca(2+)] measured with other methods and determination of Ca(2+) transport stoichiometry. Here, we review the construction of Ca(2+)-selective microelectrodes, their physical characteristics, and their use in self-referencing mode to calculate Ca(2+) flux. We also discuss potential complications when using them to measure Ca(2+) gradients near the boundary layers of single cells and tissues. PMID- 21035685 TI - Practical aspects of measuring intracellular calcium signals with fluorescent indicators. AB - The use of fluorescent indicators for monitoring calcium (Ca(2+)) signals and for measuring Ca(2+) concentration ([Ca(2+)]) in living cells is described. The following topics are covered in detail: (1) ratiometric and nonratiometric fluorescent indicators and the principles underlying their use, (2) techniques for loading Ca(2+) indicators and Ca(2+) buffers into living cells, (3) calibration of indicator fluorescence intensity measurements to yield values of intracellular [Ca(2+)], (4) analysis of nonratiometric fluorescence intensity data and caveats relating to their interpretation, (5) techniques for manipulating intracellular and extracellular [Ca(2+)], and (6) the use of fluorescent indicators to monitor Ca(2+) signals in mitochondria. The chapter aims to present these fundamental topics in a manner that is practically useful and intuitively accessible. The origins of key mathematical equations used in the article are outlined in two appendices. PMID- 21035687 TI - Patch clamp methods for studying calcium channels. AB - The patch clamp technique, which was introduced by Neher and Sakmann and their colleagues in 1981, has allowed electrophysiologists to record ion channel activity from most mammalian cell types. When well-established precautions are taken to minimize electrical and mechanical fluctuations, current transients as small as 0.5pA and as brief as 0.5ms can be measured reliably in cell-attached patches of plasma membrane with a polished glass pipette when it forms a giga-ohm seal with the membrane. In many cases, this is sufficient to watch individual channel proteins open and close repeatedly in real time on metabolically intact cells. No other technique currently provides a more precise or detailed view of the function and regulation of calcium channel gating. If antibiotics are added to the pipette to permeabilize the membrane underneath to small monovalent cations, thereby allowing the entire cell to be voltage-clamped without disrupting its contents, the integrated activity of all the calcium channels in the surface membrane can be measured. PMID- 21035686 TI - Genetically encoded probes for measurement of intracellular calcium. AB - Small, fluorescent, calcium-sensing molecules have been enormously useful in mapping intracellular calcium signals in time and space, as chapters in this volume attest. Despite their widespread adoption and utility, they suffer some disadvantages. Genetically encoded calcium sensors that can be expressed inside cells by transfection or transgenesis are desirable. The last 10 years have been marked by a rapid evolution in the laboratory of genetically encoded calcium sensors both figuratively and literally, resulting in 11 distinct configurations of fluorescent proteins and their attendant calcium sensor modules. Here, the design logic and performance of this abundant collection of sensors and their in vitro and in vivo use and performance are described. Genetically encoded calcium sensors have proved valuable in the measurement of calcium concentration in cellular organelles, for the most part in single cells in vitro. Their success as quantitative calcium sensors in tissues in vitro and in vivo is qualified, but they have proved valuable in imaging the pattern of calcium signals within tissues in whole animals. Some branches of the calcium sensor evolutionary tree continue to evolve rapidly and the steady progress in optimizing sensor parameters leads to the certain hope that these drawbacks will eventually be overcome by further genetic engineering. PMID- 21035688 TI - Nuclear patch-clamp recording from inositol 1,4,5-trisphosphate receptors. AB - Inositol 1,4,5-trisphosphate receptors (IP(3)R) are ubiquitous intracellular Ca(2+) channels. They are regulated by IP(3) and Ca(2+) and can thereby both initiate local Ca(2+) release events and regeneratively propagate Ca(2+) signals evoked by receptors that stimulate IP(3) formation. Local signaling by small numbers of IP(3)R underpins the utility of IP(3)-evoked Ca(2+) signals as a ubiquitous signaling pathway. The physiological impact of Ca(2+) release by very small numbers of IP(3)R underscores the necessity to understand the behavior of IP(3)R at the single-channel level. In addition, and in common with analyses of every other ion channel, single-channel analyses have the potential to define the steps linking IP(3) binding to channel opening. Patch-clamp recording, by resolving the openings and closings of single channels with exquisite temporal resolution, is the most powerful technique for analysis of single-channel events. It has contributed enormously to the understanding of gating and desensitization/inactivation of numerous ion channels. However, most IP(3)R reside within intracellular membranes, where they are inaccessible to conventional patch-clamp recording methods. Here, we describe the application of nuclear patch-clamp methods to single-channel analyses of native and recombinant IP(3)R. PMID- 21035689 TI - Confocal and multiphoton imaging of intracellular Ca(2+). AB - This chapter compares the imaging capabilities of a range of systems including multiphoton microscopy in regard to measurements of intracellular Ca(2+) within living cells. In particular, the excitation spectra of popular fluorescent Ca(2+) indicators are shown during 1P and 2P excitation. The strengths and limitations of the current indicators are discussed along with error analysis which highlights the value of matching the Ca(2+) affinity of the dye to a particular aspect of Ca(2+) signaling. Finally, the combined emission spectra of Ca(2+) and voltage sensitive dyes are compared to allow the choice of the optimum combination to allow simultaneous intracellular Ca(2+) and membrane voltage measurement. PMID- 21035690 TI - The use of aequorins to record and visualize Ca(2+) dynamics: from subcellular microdomains to whole organisms. AB - In this chapter, we describe the practical aspects of measuring [Ca(2+)] transients that are generated in a particular cytoplasmic domain, or within a specific organelle or its periorganellar environment, using bioluminescent, genetically encoded and targeted Ca(2+) reporters, especially those based on apoaequorin. We also list examples of the organisms, tissues, and cells that have been transfected with apoaequorin or an apoaequorin-BRET complex, as well as of the organelles and subcellular domains that have been specifically targeted with these bioluminescent Ca(2+) reporters. In addition, we summarize the various techniques used to load the apoaequorin cofactor, coelenterazine, and its analogs into cells, tissues, and intact organisms, and we describe recent advances in the detection and imaging technologies that are currently being used to measure and visualize the luminescence generated by the aequorin-Ca(2+) reaction within these various cytoplasmic domains and subcellular compartments. PMID- 21035691 TI - [Patient safety, an area of competence and a training opportunity for family and community medicine residents]. PMID- 21035692 TI - Asymptomatic peripheral arterial disease in type 2 diabetes patients: a 10-year follow-up study of the utility of the ankle brachial index as a prognostic marker of cardiovascular disease. AB - BACKGROUND: Our aim was to evaluate the relationship between asymptomatic peripheral arterial disease, diagnosed only by the ankle brachial index (ABI), and cardiovascular disease (CVD) after a 10-year follow-up period in patients with type 2 diabetes. METHODS: In 1996, the ankle brachial index was measured in 262 patients with type 2 diabetes. During the 10-year follow-up period (mean follow-up time, 7.7 years), all nonfatal cardiovascular events and mortality were recorded. RESULTS: A total of 52 patients died during the follow-up time. The mortality of the patients with normal (0.91-1.24) and abnormal ABI (<=0.90) at the beginning of the study was 16.8% and 52.8%, respectively (p < 0.05). The incidence rate of fatal and nonfatal CVD was 26.9 (95% confidence intervals [CI]: 20.7-37.3) for the patients with a normal baseline ABI and 81.9 (95% CI: 50.9 131.8) for those with an abnormal baseline ABI. An abnormal baseline ABI was associated with a greater risk of CVD (hazard ratio = 2.32; 95% CI: 1.27-4.22). CONCLUSION: ABI values <=0.9 in patients with type 2 diabetes mellitus and no history of intermittent vascular claudication or rest pain were associated with a higher risk of coronary or cerebrovascular morbidity and mortality. PMID- 21035693 TI - Remote endarterectomy versus supragenicular bypass surgery for long occlusions of the superficial femoral artery: medium-term results of a randomized controlled trial (the REVAS trial). AB - BACKGROUND: To investigate the optimal surgical treatment, remote superficial femoral artery endarterectomy (RSFAE) or supragenicular bypass, for Transatlantic Inter-Society Consensus (TASC) C and D lesions of the superficial femoral artery. Medium-term results will be presented. METHODS: The study randomized 116 patients, 61 to RSFAE and 55 to supragenicular bypass surgery. Indications for surgery were claudication in 77, rest pain in 21, or tissue loss in 18. RESULTS: Primary patency after 3 years of follow-up was 47% for RSFAE and 60% for bypass (p = 0.107), assisted primary patency was 63 and 69% (p = 0.406), and secondary patency was 69 and 73% (p = 0.541), respectively. For venous (n = 25) and prosthetic grafts (n = 30) at 3-year follow-up, primary patency was 65% and 56 versus 47% for RSFAE (p = 0.143), assisted primary patency was 84% and 56 versus 63% for RSFAE (p = 0.052), and secondary patency was 89% and 59 versus 69% for RSFAE (p = 0.046), respectively. Limb salvage was 97% after RSFAE and 95% after bypass surgery (p = 0.564). CONCLUSION: RSFAE is a minimally invasive option for surgical repair of TASC C and D superficial femoral artery obstructions, with assisted primary and secondary patency rates comparable with bypass surgery. Venous bypass grafting is superior to both RSFAE and polytetrafluoroethylene grafting, but only 45% of patients had a sufficient saphenous vein available. If the saphenous vein is not applicable, RSFAE should be considered because it is less invasive and prosthetic graft material can be avoided. PMID- 21035694 TI - Long-term results of distal-origin bypass after prior femoro-popliteal angioplasty. AB - BACKGROUND: To investigate whether prior staged percutaneous transluminal angioplasty of the femoro-popliteal segment influences long-term results of distal bypass grafts. METHODS: Between October 1987 and January 2009, 261 distal origin grafts for critical limb ischemia were performed at a single institution. A total of 223 grafts had angiographic no inflow lesions (-PA-group). Additionally, 38 grafts were performed staged within 30 days after percutaneous femoro-popliteal angioplasty (+PA-group) because of 28 TASC A (73%) and 10 TASC B (27%) lesions. Postoperative graft surveillance was performed at 3, 6, 12, and 18 months, then annually thereafter. Treatment groups were compared with Kaplan Meier analysis. RESULTS: Follow-up ranged from 1 to 198 months (median, 34 months). The 5-year primary patency was 73% for the +PA-group and 62% for the -PA group (p = 0.20). Assisted primary patency for the +PA-group at 5 years was 80% and for the -PA-group was 70% (p = 0.17). The corresponding secondary patency at 5 years was 84% for the +PA-group and 71% for the -PA-group (p = 0.12), respectively. Limb salvage and amputation free survival at 5 years were 84% and 46% for the +PA-group, and 81% and 37% for the -PA-group, respectively (p = 0.57, 0.92). Bypass-threatening stenosis of the inflow-vessel was detected for four (10.5%) cases in the +PA-group and for 21 (8%) in the -PA-group. CONCLUSION: Long term results of distal origin grafts performed after femoro-popliteal angioplasty because of TASC A and B lesions are comparable with those observed in distal origin grafts without proximal stenosis. Distal origin bypass grafting is not compromised by prior endovascular treatment of the inflow-vessel. PMID- 21035695 TI - Preoperative carotid duplex findings predict carotid stump pressures during endarterectomy in symptomatic but not asymptomatic patients. AB - BACKGROUND: Carotid stump pressure (CSP) is frequently measured to determine the need for shunt use during carotid endarterectomy (CEA). We hypothesized that the preoperative carotid duplex examination correlates with preoperative symptoms and intraoperative CSP. METHODS: Patients undergoing CEA over a 7-year period were identified from our vascular registry. CEA was performed with selective shunting on the basis of intraoperative CSP <30 mm Hg regardless of symptoms or contralateral internal carotid artery (ICA) stenosis. The preoperative duplex was categorized by ipsilateral and contralateral ICA diameter-reduction stenosis (<15%, 15-45%, 45-70%, 70-99% [severe] and occluded), and the direction of vertebral artery flow. The relationships among preoperative duplex findings, symptom status, and CSP were evaluated using unpaired t-test and Chi-square analysis. RESULTS: A total of 303 CEAs were performed. Stump pressures were documented in 284 patients, which comprised the study population. Asymptomatic severe stenosis was the indication for CEA in 179 cases (59.1%). Symptomatic patients (Sx) had significantly lower stump pressures than asymptomatic (ASx) patients (40.72 +/- 16.27 vs. 45.8 +/- 17.64 mm Hg, p = 0.0167). Fifty-seven patients (19%) had contralateral severe ICA stenosis or occlusion. Contralateral ICA stenosis or occlusion had significantly lower CSP than those with lesser degrees of stenosis (39.24 +/- 15 vs. 44.82 +/- 17.62 mm Hg, p = 0.0267). Contralateral ICA severe stenosis or occlusion correlated with lower CSP in Sx patients (32.05 +/- 8.24 vs. 42.92 +/- 16.95 mm Hg, p = 0.038) but not in ASx patients (43.2 +/- 16 vs. 46.29 +/- 17.5 mm Hg, p = 0.39). CSP was <30 mm Hg in 63% of Sx patients and 24% of ASx patients (p = 0.012). Overall shunt usage was 84/2,842 (9.5%). Perioperative stroke and death rate was 2.7%. Perioperative stroke did not correlate with the presence of contralateral occlusion, or severity of contralateral stenosis. CONCLUSIONS: Symptomatic patients undergoing CEA have lower stump pressures than ASx patients overall and also in the presence of contralateral disease. The incidence of perioperative stroke was not predicted by severity of contralateral disease. A strategy of selective shunting seems appropriate even in Sx patients with contralateral severe stenosis or occlusion. Although a high-risk cohort for perioperative neurologic events exists and may include those with symptomatic disease and contralateral severe stenosis or occlusion, further study is warranted to define the patients who will clinically benefit from shunt placement. PMID- 21035696 TI - Predictors of electroencephalographic changes needing shunting during carotid endarterectomy. AB - BACKGROUND: Carotid endarterectomy (CEA) is associated with a risk of cerebral ischemia during carotid clamping, hence various cerebral protection strategies, including pharmacological management and routine or selective shunting, are commonly available. This study aimed to analyze the results of CEA with intraoperative electroencephalographic (EEG) monitoring to identify factors associated with EEG changes consistent with cerebral ischemia which needed shunting. METHODS: A prospectively compiled, computerized database of all primary CEAs performed at our institution with EEG monitoring for symptomatic or asymptomatic severe carotid lesions between January 1990 and June 2009 was analyzed. RESULTS: In all, 1,914 CEA procedures were performed on 1,696 patients, of which 218 had staged bilateral CEAs. EEG changes were recorded in 392 patients (20.5%), but a shunt was inserted during 312 CEA procedures (16.3%). Multivariate analysis showed that a symptomatic presentation (odds ratio [OR], 1.37; 95% confidence intervals [CI], 1.07-1.76; p = 0.012), prior stroke (OR, 2.28; 95% CI, 1.66-3.13; p < 0.001), contralateral carotid occlusion (OR, 2.14; 95% CI, 1.18 3.91; p = 0.019), and moderate (<80%) ipsilateral carotid disease (OR, 1.95; 95% CI, 1.08-3.52; p = 0.033) predicted the need for shunting. CONCLUSIONS: EEG was an excellent detector of cerebral ischemia and a valuable tool in guiding the need for shunting. Patients who were symptomatic or had a history of stroke, a contralateral carotid occlusion, or an ipsilateral moderate carotid stenosis were more prone to EEG changes consistent with cerebral ischemia. Surgeons should consider EEG changes during clamping as an effective criterion for selective shunting. PMID- 21035697 TI - Inflammatory abdominal aortic aneurysm endovascular repair into the long-term follow-up. AB - BACKGROUND: To investigate long-term outcomes for inflammatory abdominal aortic aneurysms (IAAA) after endovascular treatment (EVAR). METHODS: Between May 1997 and January 2009, 9 male patients (Mean 67 years, range 54-75 years) with IAAA were treated with EVAR using commercially available endografts. Results were assessed using contrast-enhanced computed tomography (CT) at 3 months, 12 months, and biannually thereafter. Echo-color duplex scanning was also recommended at 3, 6, and 12 months after discharge, and annually thereafter. Primary endpoints were aneurysm-related mortality, aneurysm sac evolution, perianeurysmal fibrosis (PAF) thickness, and hydronephrosis progression. RESULTS: No aneurysm-related deaths were observed during the long-term follow-up of eight patients (one patient death unknown). Maximum aneurysm sac diameter progressively reduced in eight patients (89%) and remained unchanged in one (11%). The absolute mean reduction of the aneurysm size was 26.2%. PAF regressed in two patients (22%), reduced in five (56%), and remained unchanged in two (22%). The absolute median reduction of the PAF thickness was 55.1%. No endoleak was observed during the follow-up period. Hydronephrosis persisted in all three patients who were preoperatively diagnosed with this pathology. Survival rates were 89%, 66.7%, and 66.7% at 12, 36, and 60 months, respectively. CONCLUSIONS: This series suggests that EVAR for IAAA into the long-term is associated with a positive trend for both PAF and aneurysm diameter reduction. EVAR does not seem to offer any benefits for hydronephrosis, but seems to effectively exclude the aneurysm sac in anatomically suitable patients. PMID- 21035698 TI - APACHE III score on ICU admission predicts hospital mortality after open thoracoabdominal and open abdominal aortic aneurysm repair. AB - BACKGROUND: No prior studies, to our knowledge, have examined the performance of the Acute Physiology and Chronic Health Evaluation (APACHE) III score in predicting mortality of patients undergoing open thoracoabdominal aortic aneurysm (TAAA) or open abdominal aortic aneurysm (AAA) repair. We sought to evaluate APACHE III scores in the prediction of postoperative mortality in elective TAAA and AAA repairs. METHODS: Over a 9-year period (July 1998 through June 2007), prospective data (demographics, admitting diagnosis, APACHE III score, intensive care unit [ICU] and hospital length of stay, ICU and hospital mortality) were collected by a dedicated APACHE III coordinator for all patients admitted to a tertiary academic surgical ICU (20 beds). Observational and comparative analyses were performed. Emergent repairs for ruptured aneurysms were excluded from the study. RESULTS: Forty-one patients underwent open elective repair of TAAA and 404 underwent open elective repair of AAA. Mean age of the TAAA group was 63.4 +/- 9.8 years and the AAA group was 70.3 +/- 8.3 years. Mean APACHE III score was 54 (range: 10-103) for the TAAA group and 45 (range: 11-103) for the AAA group. The in-hospital mortality rate for TAAA patients was 4.9% (n = 2) and for AAA patients was 2.0% (n = 8). Mean APACHE III scores on ICU admission were significantly greater in nonsurvivors versus survivors (79 vs. 45, p < 0.0001). For the entire patient cohort, the APACHE III score on ICU admission was an excellent discriminator of hospital mortality (receiver operating characteristic and area under the curve 0.92 [standard error of 0.05, 95% CI: 0.83-1.0]). CONCLUSIONS: APACHE III is an accurate predictor of survival to hospital discharge in both open elective TAAA and AAA repairs. PMID- 21035699 TI - Open surgical repair and endovascular treatment in adult coarctation of the aorta. AB - BACKGROUND: The aim of this study was to compare the results of endovascular therapy (covered stenting) with surgical technique to repair aortic coarctation in adults. METHODS: A prospective study of 11 patients who were treated during the past 10 years was carried out. Of these, five patients underwent endoprosthesis (group A) and six an open surgical repair (group B). Follow-up comprised monitoring of the blood pressure, echocardiography, and computed tomography and magnetic resonance angiographic studies. RESULTS: The mean age of the patients was 46 years (range: 17-67 years) and the mean follow-up was 52.6 months (range: 1-117 months; 32.3 for group A vs. 69.7 for group B; p = 0.01). Two cases in group A were recoarctations after child angioplasty. The rate of postoperative complications was 27.7% (one hemothorax for group A vs. one pneumothorax and one hemothorax for group B); however, mortality did not occur. The success rate of the endovascular technique was 80%. The stay in the intensive care unit was 2.3 days with significant differences (one group A vs. three group B; p = 0.01), whereas length of hospital stay was 11 days (7.8 group A vs. 11.83 group B; p = 0.17). The pressure gradient across the stenosis decreased by 21.9 +/- 3.7 mm Hg (24.5 +/- 4.3 group A vs. 33 +/- 3.2 group B). Six patients (54.5%) showed persistent hypertension (80% group A vs. 33% group B), with a mean residual pressure gradient of 23.4 +/- 4.3 mm Hg (22.5 +/- 5.4 group A vs. 22 +/- 2.1 group B; p = 0.58). CONCLUSIONS: Short- and medium-term results of the endovascular therapy are similar, with shorter stay in the intensive care unit and higher necessity of antihypertensive treatment. Echocardiography and Doppler aortic coarctation gradients slightly higher than 20 mm Hg are usual during follow-up. PMID- 21035700 TI - Post-endovascular aneurysm repair patient outcomes and follow-up are not adversely impacted by long travel distance to tertiary vascular surgery centers. AB - BACKGROUND: To determine whether patient adherence to follow-up and patient outcomes after endovascular aneurysm repair (EVAR) are affected by the distance between a patient's residence and a tertiary care treatment center. METHODS: A retrospective review of 136 consecutive patients undergoing EVAR at the New Mexico Veterans Affairs Medical Center over a 7-year period was conducted. Patients were stratified as living within a 100-mi radius of the treatment center (group 1) and those living outside this radius (group 2). Follow-up included clinic visits and computed tomography scans at 1 month after discharge, every 6 months for 2 years, and then yearly. Incomplete follow-up was defined if two or more consecutive appointments were missed. Survival and graft-related complication rates were analyzed for both the patient groups. RESULTS: Of the 136 patients, 10 patients died from nonaneurysm-related causes less than 1 year after their EVAR procedures, and hence were not a part of the study. Of the surviving patients, 44% lived within a 100-mi radius of the treatment center (group 1), and 56% outside this 100-mi radius (group 2). The mean patient follow-up time was 52.1 +/- 25.9 months. Of the surviving patients, 15% had inadequate follow-up, yet there was no significant difference in the adequacy of follow-up for patients in group 1 compared with group 2. The incidence of major complications, defined as aneurysm rupture, conversion to open repair, myocardial infarction, and stroke, was not statistically different in group 1 versus group 2 (5.0% vs. 11.8%, p = 0.23). Of the five patients (3.7%) who died as a result of abdominal aortic aneurysms related causes, three were in group 1 and two in group 2. CONCLUSIONS: Distance from a tertiary care center is not a limiting factor in patient adherence to follow-up, patient graft-related morbidity, or patient survival, likely because of the Albuquerque VA Medical Center's electronic tracking of patients and provision of travel vouchers. PMID- 21035701 TI - Results of single- and two-vessel mesenteric artery stents for chronic mesenteric ischemia. AB - BACKGROUND: To describe the outcomes of single- and two-vessel mesenteric artery stents in patients with chronic mesenteric ischemia (CMI). METHODS: We reviewed 101 patients (41 men and 60 women; mean age, 73 +/- 13 years) treated with mesenteric artery stents for atherosclerotic CMI between 1998 and 2008. Clinical data and outcomes were reviewed in patients treated with single superior mesenteric artery (SMA) stent (group A) or two-vessel celiac artery (CA) and SMA stent (group B). Isolated CA stenting was analyzed as a separate group (group C). End-points were taken as differences in morbidity and mortality and freedom from recurrent symptoms and reinterventions. RESULTS: There were 61 patients in group A, 24 in group B, and 16 in group C. All three groups had similar demographics, cardiovascular risk factors, and clinical presentation. There were no differences in early mortality (2%, 4%, and 0%), morbidity (18%, 26%, and 12%), and symptom relief (95%, 78%, and 100%) between groups A, B, and C, respectively (p value was not significant). Mean follow-up was 41 +/- 17 months. Freedom for reintervention at 1 and 3 years was similar among patients in groups A (86 +/- 5% and 50 +/- 9%), B (67 +/- 11% and 67 +/- 11%), and C (63 +/- 13% and 63 +/- 13%), respectively (p value was not significant). There were no significant differences in freedom from restenosis at 1 and 3 years among patients in groups A (54 +/- 7% and 44 +/- 9%), B (47 +/- 12% and 39 +/- 12%), and C (43 +/- 13% and 34 +/- 13%), respectively. Primary and secondary patency rates at 3 years were 57% and 96% for SMA and 61% and 87% for CA stents, respectively (p value was not significant). CA stent alone was associated with symptom recurrence in 6 of 16 patients (38%), as compared with the recurrence rate of 18% (11 of 61) in patients who underwent SMA stent placement (p = 0.06). CONCLUSION: Two-vessel CA and SMA stenting do not reduce the incidence of recurrent symptoms or reinterventions when compared with single-vessel SMA stents in patients with CMI. CA stent alone carries a high risk of recurrence. PMID- 21035702 TI - A new therapeutic approach to congenital pelvic arteriovenous malformations. AB - BACKGROUND: Internal iliac arteriovenous malformations (AVM) are difficult to treat. Arterial embolization is chosen in most cases but the angio-architecture of these arteriovenous shunts can provide an explanation for the several reported failures. We report the long-term results of peroperative intravenous embolization. METHODS: Between the years 1980 and 2008, seven patients were treated for complex and symptomatic internal AVM. These patients underwent a surgery which involved massive embolization of the venous hypogastric compartment, followed by the ligation of the hypogastric vein at its origin. RESULTS: There were no deaths reported in this group. The mean follow-up was 7 years (range: 10 months-12 years), with no cases of recurrences found. Computed tomographic scans of controls with reconstruction did not show any residual arteriovenous shunts. CONCLUSION: Intravenous embolization of the internal iliac AVM is a therapeutic strategy which is well adapted to the special angio architecture of the arteriovenous shunts. Clinical and anatomic results have confirmed the validity of this strategy. PMID- 21035703 TI - Management of lower extremity wounds in patients with peripheral arterial disease: a stratified conservative approach. AB - BACKGROUND: Traditional wound care algorithms include aggressive detection of peripheral arterial disease (PAD) and treatment with revascularization for all patients with PAD and lower extremity wounds. Not every patient with PAD and a wound meets Transatlantic Inter-Society Consensus (TASCII) criteria for critical limb ischemia. We hypothesize that a conservative approach to selected patients with PAD and lower extremity wounds may be safe, provide acceptable limb salvage, and that failure of this approach does not translate into increased limb loss. METHODS: Veterans referred with PAD and nonhealing ulcers/wounds were prospectively enrolled into our Prevention of Amputation Care Team program. Patients were stratified according to management strategies which included revascularization, primary amputation, palliative limb care, and aggressive local care without revascularization (conservative group). Patients were assigned to conservative management group on the basis of transcutaneous oxygen measurement (TcpO2) and ankle-brachial index (ABI). Healing rates, need for "late" revascularization, major amputation rates, and survival of this conservative group were analyzed in terms of ABI and ankle pressures. RESULTS: Between January 2006 and March 2009, a total of 190 lower extremity wounds in 178 patients with PAD were analyzed. Forty-nine patients with 52 wounds (27.9%) were deemed candidates for conservative treatment. During mean follow-up of 14.5 months, complete wound healing was documented in 33 patients (35 wounds: 67%). Mean time to complete wound healing was 4.5 months. Predictors of healing included mean ABI (0.62 vs. 0.42 [p < 0.001]) and ankle pressures >70 mm Hg (p = 0.025). Sixteen patients (17 wounds: 33%) were not healed at the time of analysis. Of these, three patients (four wounds: 8%) showed active healing and 13 (13 wounds: 25%) failed conservative management. Nine patients (9 wounds: 17%) underwent late revascularization. There was one case of amputation (2%) and six cases of mortalities (12.2%). There was no increase in the rates of limb loss and mortality in patients who failed conservative management and underwent "late" revascularization. CONCLUSIONS: Conservative management of lower extremity nonhealing wounds in selected patients with PAD is successful in over two-thirds of the patients. The failure of conservative management does not increase mortality or amputation rates. When the TcPO2 is >30 mm Hg, the ABI and the TASC II definition of critical limb ischemia predict wound healing and should be key factors in considering conservative therapy. PMID- 21035704 TI - Local intra-arterial thrombolysis with urokinase for acute ischemic stroke before and after the approval of intravenous tissue plasminogen activator treatment in Taiwan. AB - BACKGROUND: Local intra-arterial thrombolysis (LIT) has been previously suggested as an effective therapy for acute ischemic stroke. In this study, we describe our experience of using LIT for the treatment of Taiwanese patients with ischemic stroke at different vascular locations, before and after Alteplase was approved as a first-line treatment in Taiwan. The criteria required for the initiation of LIT have become more stringent after the approval of Alteplase (AA). METHODS: A retrospective analysis of medical records was conducted for 20 ischemic stroke patients treated with LIT; including 10 patients treated before and 10 patients treated after AA (we did not treat any of the patients in this study with AA). Urokinase was used for LIT treatment. Outcome measures included patient demographics, clinical characteristics, and clinical outcomes before and after LIT. Clinical outcomes were evaluated using four different stroke scales. RESULTS: The median National Institutes of Health stroke scale score (NIHSS) before treatment was reported to be 19.2 (range: 8-30). After AA, only one patient who had an occluded internal carotid artery (ICA) was treated with LIT. Among the 20 patients, 11 (55%) (five before AA and six after AA) reported having favorable or good clinical outcomes within 3 months of treatment, whereas five reported having poor outcomes (three before AA and two after AA), and the rest four patients died following treatment (two before AA and two after AA). Arterial recanalization was reported as complete in 10 patients (50%; seven middle cerebral artery [MCA] and three basilar artery; six before AA and four after AA), as incomplete in four patients (20%; one MCA and three basilar artery; one before AA and three after AA), and it failed in the remaining six patients (30%; two MCA and four ICA; three before AA and three after AA). Five patients (one MCA and four ICA) in whom recanalization had failed reported having poor outcomes, including one ICA patient who subsequently succumbed to the illness. Intracranial hemorrhagic and intraventricular hemorrhage transformation occurred in three and two patients, respectively. A case of intraventricular hemorrhage transformation after AA was also reported. CONCLUSION: On the basis of our experience, we found that LIT was of limited value in patients with ICA occlusion before AA approval. After AA, the outcomes in acute stroke patients, who were receiving urokinase therapy and who were carefully selected on the basis of the site of occlusion, were improved. PMID- 21035705 TI - Mortality after hospital admission for ruptured abdominal aortic aneurysm. AB - BACKGROUND: The purpose of this study is to quantify age- and gender-specific mortality risks for patients hospitalized for ruptured abdominal aortic aneurysm (rAAA). METHODS: The mortality risks for 28-day, 1-year, and 5-year were derived from a retrospective nation-wide cohort study of patients who were first hospitalized for rAAA in 1997 or 2000, formed through linkage of the Hospital Discharge Register with the Dutch population register. The Hospital Discharge Register contains a record for each hospital admission, giving information about patient demographics and diagnosis. The population register contains information on patient demographics and the mortality status of all registered persons in The Netherlands. Relations between gender and mortality within specific age groups were assessed with chi-square tests. Associations between age, gender, comorbidities, and mortality were studied in multivariate analysis with Cox regression. RESULTS: A total of 1,463 patients hospitalized for rAAA were identified (86% males). Mean age was higher in women than in men (79 vs. 72 years; 95% CI of difference: 5.0-7.4). Mortality risks at 28-day, 1-year, and 5 year increased significantly with age (28-day: from 36 to 91% in men and 59 to 92% in women; 5-year: from 51 to 97% in men and 79 to 96% in women). In patients aged <80 years, mortality risks were significantly higher in women than in men. Age (HR: 1.04; 95% CI: 1.03-1.05), previous hospitalization for congestive heart failure (HR: 1.55; 95% CI: 1.06-2.26), and cerebrovascular disease (HR: 1.60; 95% CI: 1.16-2.21) were significant predictors of short- and long-term mortality. CONCLUSIONS: Mortality risks after hospitalization for rAAA clearly increase by age and are higher in women than in men in patients aged <80 years. Because of the major effect of age and gender, future studies should consider reporting absolute mortality risks stratified by age and gender, instead of simply presenting overall mortality risks. PMID- 21035706 TI - Embolic strokes after peripherally inserted central catheter placement. AB - Peripherally inserted central catheters (PICCs) have become popular for a range of indications in both inpatient and outpatient settings. Though PICCs are generally safe, they can be associated with a variety of complications. We present here a case with embolic strokes due to inadvertent arterial placement of PICC, an uncommon but potentially life-threatening complication. A high clinical suspicion with critical evaluation of radiographs is indispensable for suspecting misplaced PICCs. PMID- 21035707 TI - Skiing and intermittant claudication: an aberrant presentation. AB - Lower extremity peripheral arterial disease frequently presents with intermittent claudication, typically manifest in lower extremity pain or cramping associated with exercise, generally walking. Occasionally early onset of disease can be associated with running. This report describes the unusual presentation of leg pain associated with skiing and relieved by cessation of skiing immediately caused by focal iliac artery stenosis. PMID- 21035708 TI - Lifesaving kissing stent for pulmonary trunk stenosis due to primary angiosarcoma. AB - A 62-year-old diabetic female was referred to our institution with a 6-month history of pulmonary hypertension and worsening right-sided heart failure. Computed tomography of the chest and pulmonary angiogram revealed a pulmonary artery mass. Due to patient's frail state, palliative kissing stenting to both pulmonary arteries was performed with optimal angiographic results and overt clinical improvement. At 5 month follow-up, both stents were patent and adequate lung perfusion was observed bilaterally. PMID- 21035709 TI - Cervical cystic lymphangioma in a patient with blue rubber bleb nevus syndrome: clinical case report and review of the literature. AB - We present the case of a 9-year-old boy diagnosed with blue rubber bleb nevus syndrome, who showed a very large left cervical cystic lymphangioma. He was previously subjected to various treatments for lesions in the intestinal tract including blood transfusions for anemia, sclerosis, enterotomies or resections. The tumor was resected without any complications and the anatomopathologic report confirmed this diagnosis. The blue cavernous hemangioma syndrome (or blue rubber bleb nevus syndrome) is a rare disease characterized by cavernous angiomas involving the skin and gastrointestinal tract. Several cases of cystic lymphangiomas associated with this syndrome have been published recently and lymphomatous differentiation has been identified in the cells of cutaneous lesions. Given their common embryological origin, we underscore the importance of bearing in mind that it is possible for different types of vascular malformations to coexist in the same patient. PMID- 21035710 TI - Popliteal vein thrombosis after radiofrequency ablation of greater saphenous vein for varicose vein. AB - Percutaneous endovenous techniques, such as radiofrequency ablation (RFA), have become the preferred method for treatment for varicose veins associated with great saphenous vein (GSV) insufficiency. Reports have shown safety and efficacy of these techniques with relatively few complications. Deep venous thrombosis after RFA is rare and usually involves extension of thrombus from great saphenous vein to common femoral vein, hence the requirement for postoperative ultrasound. We report a case of symptomatic popliteal vein thrombosis after RFA of GSV requiring anti-coagulation. PMID- 21035711 TI - Pseudoaneurysm of the gastroduodenal artery secondary to chronic pancreatitis. AB - Although pseudoaneurysms are a rare complication of chronic pancreatitis, they are potentially serious both because of the events they can lead to and the diagnostic challenges they may pose. Historically, they used to be treated surgically, through ligation and/or resection; it was not until the last decade that scarcely invasive percutaneous endovascular procedures were introduced. This article reports the case of a patient with chronic pancreatitis presenting with severe upper digestive hemorrhage caused by the rupture of a pseudoaneurysm of the gastroduodenal artery. The patient was successfully treated using selective embolization. PMID- 21035712 TI - A case of abdominal aortic aneurysm associated with L-shaped crossed-fused renal ectopia. AB - Genitourinary anomalies are a tremendous challenge for the vascular surgeon, especially when dealing with an abdominal aortic aneurysm. We report a case of crossed-fused renal ectopia, a rare anomaly accompanied by abdominal aortic aneurysm. Bilateral renal arteries and one aberrant artery from the right common iliac artery supply the ectopic kidney. Because renal ischemia during aortic reconstruction can be a serious problem, we reconstructed a temporary right axillo-left renal artery bypass graft first, then reimplanted the aberrant renal artery. When choosing the procedure for renal preservation, preoperative multidetector-row computed tomography was useful to plan the operative strategy. PMID- 21035713 TI - Unsuccessful treatment of a collapsed thoracic stent graft by Palmaz stent. AB - A Gore TAG Excluder stent graft was deployed in a 35-year-old woman for an isthmic saccular aneurysm. At 12-hour follow-up, we diagnosed a proximal collapse. A Palmaz stent was used to reopen the proximal segment. Two months later, she presented with a transient ischemic attack (embolic process) related to a suboptimal apposition of the Palmaz stent in the distal aortic arch. This led to open surgical replacement of the ascending aorta and aortic arch with reimplantation of the supraaortic branches. Reopening of a stent graft collapse with a Palmaz stent might be a short-term solution; however, its presence can lead to embolic complications. PMID- 21035714 TI - Esophageal necrosis after endoprosthesis for ruptured thoracoabdominal aneurysm type I: can long-segment stent grafting of the thoracoabdominal aorta induce transmural necrosis? AB - BACKGROUND: To study the pathophysiology of esophageal necrosis after endoprosthesis was performed for a ruptured aneurysm and to define preventive measures and possible treatment options. METHOD: A 72-year-old man with thoracoabdominal aneurysm type I and dysphagia underwent an emergent carotico carotid bypass in combination with thoracic endovascular aortic aneurysm repair starting at a point distal to the brachiocephalic trunk and ending proximal to the superior mesenteric artery. On day 12, a decortication was performed for treating an infection in the remaining hematoma. However, further deterioration occurred as a result of mediastinitis secondary to the transmural necrosis of the middle third of the esophagus combined with accompanying mediastinitis. The patient's family refused to give consent for further treatment by esophagectomy. He died 24 days after the initial operation. CONCLUSION: Dysphagia aortica, mucosal abnormalities on esophagogastroscopy, and mediastinal compression by hematoma at the time of rupture draws our attention toward ischemia of the esophagus after thoracic endovascular aortic aneurysm repair. Repeated esophagoscopy can provide us with the opportunity to act before full thickness necrosis and mediastinitis occur. PMID- 21035715 TI - Baroreceptor failure syndrome after bilateral carotid body tumor surgery. AB - A 41-year-old healthy man was diagnosed with bilateral carotid body tumors. The patient had a staged surgical removal of the tumors approximately 8 months apart. Postoperative recovery was uneventful after removal of the first and largest tumor; however, after removal of the second tumor, the patient developed tachycardia and hypertension. He was diagnosed with baroreceptor failure syndrome after ruling out other possible causes. Baroreceptor failure syndrome is a rare and important complication known to be associated with many conditions, one of them being inadvertent baroreceptor denervation during bilateral carotid body tumor resection. Medical management of this condition is necessary to prevent cerebrovascular events; thus, it is important for the surgeon and the internist to recognize and treat it aggressively. PMID- 21035716 TI - Therapy of acute massive pulmonary embolism associated with Klippel-Trenaunay syndrome. AB - Acute massive pulmonary embolism (PE) is a life-threatening event. Before the era of cardiopulmonary bypass, acute pulmonary embolectomy had been historically attempted in patients with severe hemodynamic compromise. The Klippel-Trenaunay syndrome (KTS) represents a significant life-long risk for major thromboembolic events. We present two young patients with Klippel-Trenaunay syndrome who survived surgical embolectomy after massive PE and cardiopulmonary resuscitation, with good postoperative recovery. Even though the role of surgical embolectomy in massive PE is not clearly defined, with current technology it can be life saving and can lead to a complete recovery, especially in young patients as described in this study. PMID- 21035717 TI - Hybrid-fenestrated aortic aneurysm repair: a novel technique for treating patients with para-anastomotic juxtarenal aneurysms. AB - This article describes a novel technique that combines off-label endovascular methods with an open surgical debranching procedure to facilitate repair of a para-anastomotic juxtarenal aortic aneurysm. We present a case of recurrent aortic aneurysmal disease 10 years after infrarenal tube graft repair. The aneurysm was treated in two stages; first by retrograde aortobirenal bypass with a bifurcated graft. Subsequently, fenestrated endografting was performed with a custom-altered TX-2 thoracic stent graft (COOK, Bloomington, IN), with fenestrations for both the celiac and superior mesenteric arteries. As compared with a purely open approach, this technique offers an alternative for managing juxtarenal aneurysms with less physiologic insult. PMID- 21035718 TI - Quantitative relationship between vascular kinking and twisting. AB - A wide variety of factors causing vascular thrombosis in the microvascular free flap reconstruction have been encountered. The most frequent situation in our experiences has been vascular kinking because of improper positioning. It has been reported that the best way to avoid kinking is to place the vessels at a neutral axis. However, curving the pedicles to match the recipient vessels cannot be avoided, especially in head and neck reconstruction with a large flap and long pedicle. According to our clinical experiences, the curved vascular pedicle needs rotation in its axis from the neutral position to avoid kinking. Furthermore, we noted that the number of loops equals the number of axial rotations of 360 degrees . We propose that these experiences and ideas can have wide applications in various fields of vascular surgery. PMID- 21035719 TI - Concerns on article: The impact of isolated tibial disease on outcomes in the critical limb ischemic population. Ann Vasc Surg 2010;24:349-359. PMID- 21035720 TI - A paragastric gossypiboma with caval thrombosis. PMID- 21035721 TI - Delayed dysphagia after endovascular repair of thoracic aortic aneurysm. PMID- 21035722 TI - Historical overview of varicose vein surgery. PMID- 21035723 TI - Keeping pneumonia's vaccines effective. PMID- 21035724 TI - Using surrogates to bypass missing catalytic components. AB - Bryostatin is a natural product that has many medically promising biological activities. Understanding how bryostatin is assembled by the producting symbiotic bacterium has been hampered by the limited availability of genetic information. In the new report, Buchholz et al. (2010) circumvented this issue by using surrogates to replace missing catalytic components. PMID- 21035725 TI - CDK9 inhibitors push cancer cells over the edge. AB - The trouble with CDK active-site inhibitors is their tendency to have off-target effects. This is not surprising, as the ATP binding sites of most protein kinases are very similar. Wang et al. (2010) have used some clever screening approaches to identify selective CDK9 inhibitors that drive cancer cells into apoptosis. PMID- 21035726 TI - Positive reinforcement for viruses. AB - Virus-cell membrane fusion requires a critical transition from positive to negative membrane curvature. St. Vincent et al. (2010), in PNAS, designed a class of antivirals that targets this transition. These rigid amphipathic fusion inhibitors are active against an array of enveloped viruses. PMID- 21035727 TI - Miniaturization and parallelization of biological and chemical assays in microfluidic devices. AB - Microfluidic systems are an attractive solution for the miniaturization of biological and chemical assays. The typical sample volume can be reduced up to 1 million-fold, and a superb level of spatiotemporal control is possible, facilitating highly parallelized assays with drastically increased throughput and reduced cost. In this review, we focus on systems in which multiple reactions are spatially separated by immobilization of reagents on two-dimensional arrays, or by compartmentalization in microfabricated reaction chambers or droplets. These systems have manifold applications, and some, such as next-generation sequencing are already starting to transform biology. This is likely the first step in a biotechnological transformation comparable to that already brought about by the microprocessor in electronics. We discuss both current applications and likely future impacts in areas such as the study of single cells/single organisms and high-throughput screening. PMID- 21035728 TI - The kalimantacin/batumin biosynthesis operon encodes a self-resistance isoform of the FabI bacterial target. AB - BatG is a trans-2-enoyl-ACP reductase, encoded in the kalimantacin/batumin (kal/bat) biosynthesis operon. It is not essential for the production of the kal/bat secondary metabolite. Instead, BatG is an isoform of FabI, conferring full resistance to target bacteria. It also complements FabI in its role in fatty acid biosynthesis. The identification of FabI as the antibacterial target is important to assess clinical potential of the kalimantacin/batumin antibiotics against Staphylococcus aureus. PMID- 21035729 TI - Genetically directing E-N, N-dimethyl-L-lysine in recombinant histones. AB - A molecular understanding of the biological phenomena orchestrated by lysine N(E) methylation is impeded by the challenge of producing site-specifically and quantitatively methylated histones. Here, we report a general method that combines genetic code expansion and chemoselective reactions, for the quantitative, site-specific installation of dimethyl-lysine in recombinant histones. We demonstrate the utility of our method by preparing H3K9me2 and show that this modified histone is specifically recognized by heterochromatin protein 1 beta. Extensions of the strategy reported here will allow a range of chemoselective reactions (which have been used for residue-selective, but not site-selective protein modification) to be leveraged for site-specific protein modification. PMID- 21035730 TI - N-acylation during glidobactin biosynthesis by the tridomain nonribosomal peptide synthetase module GlbF. AB - Glidobactins are hybrid NRPS-PKS natural products that function as irreversible proteasome inhibitors. A variety of medium chain 2(E),4(E)-diene fatty acids N acylate the peptidolactam core and contribute significantly to the potency of proteasome inhibition. We have expressed the initiation NRPS module GlbF (C-A-T) in Escherichia coli and observe soluble active protein only on coexpression with the 8 kDa MbtH-like protein, GlbE. Following adenylation and installation of Thr as a T-domain thioester, the starter condensation domain utilizes fatty acyl-CoA donors to acylate the Thr(1) amino group and generate the fatty acyl-Thr(1)-S pantetheinyl-GlbF intermediate to be used in subsequent chain elongation. Previously proposed to be mediated via acyl carrier protein fatty acid donors, direct utilization of fatty acyl-CoA donors for N-acylation of T-domain tethered amino acids is likely a common strategy for chain initiation in NRPS-mediated lipopeptide biosynthesis. PMID- 21035731 TI - Structural determinants of inhibitor selectivity in prokaryotic IMP dehydrogenases. AB - The protozoan parasite Cryptosporidium parvum is a major cause of gastrointestinal disease; no effective drug therapy exists to treat this infection. Curiously, C. parvum IMPDH (CpIMPDH) is most closely related to prokaryotic IMPDHs, suggesting that the parasite obtained its IMPDH gene via horizontal transfer. We previously identified inhibitors of CpIMPDH that do not inhibit human IMPDHs. Here, we show that these compounds also inhibit IMPDHs from Helicobacter pylori, Borrelia burgdorferi, and Streptococcus pyogenes, but not from Escherichia coli. Residues Ala165 and Tyr358 comprise a structural motif that defines susceptible enzymes. Importantly, a second-generation CpIMPDH inhibitor has bacteriocidal activity on H. pylori but not E. coli. We propose that CpIMPDH-targeted inhibitors can be developed into a new class of antibiotics that will spare some commensal bacteria. PMID- 21035732 TI - Polyketide beta-branching in bryostatin biosynthesis: identification of surrogate acetyl-ACP donors for BryR, an HMG-ACP synthase. AB - In vitro analysis of natural product biosynthetic gene products isolated from unculturable symbiotic bacteria is necessary to probe the functionalities of these enzymes. Herein, we report the biochemical characterization of BryR, the 3 hydroxy-3-methylglutaryl (HMG)-CoA synthase (HMGS) homolog implicated in beta branching at C13 and C21 of the core ring system from the bryostatin metabolic pathway (Bry). We confirmed the activity of BryR using two complementary methods, radio-SDS PAGE, and Fourier transform ion cyclotron resonance-mass spectrometry (FTICR-MS). The activity of BryR depended on pairing of the native acetoacetyl BryM3 acceptor acyl carrier protein (ACP) with an appropriate donor acetyl-ACP from a heterologous HMGS cassette. Additionally, the ability of BryR to discriminate between various ACPs was assessed using a surface plasmon resonance (SPR)-based protein-protein binding assay. Our data suggest that specificity for a protein-bound acyl group is a distinguishing feature between HMGS homologs found in PKS or PKS/NRPS biosynthetic pathways and those of primary metabolism. These findings reveal an important example of molecular recognition between protein components that are essential for biosynthetic fidelity in natural product assembly and modification. PMID- 21035734 TI - Discovery and characterization of 2-anilino-4- (thiazol-5-yl)pyrimidine transcriptional CDK inhibitors as anticancer agents. AB - The main difficulty in the development of ATP antagonist kinase inhibitors is target specificity, since the ATP-binding motif is present in many proteins. We introduce a strategy that has allowed us to identify compounds from a kinase inhibitor library that block the cyclin-dependent kinases responsible for regulating transcription, i.e., CDK7 and especially CDK9. The screening cascade employs cellular phenotypic assays based on mitotic index and nuclear p53 protein accumulation. This permitted us to classify compounds into transcriptional, cell cycle, and mitotic inhibitor groups. We describe the characterization of the transcriptional inhibitor class in terms of kinase inhibition profile, cellular mode of action, and selectivity for transformed cells. A structural selectivity rationale was used to optimize potency and biopharmaceutical properties and led to the development of a transcriptional inhibitor, 3,4-dimethyl-5-[2-(4-piperazin 1-yl-phenylamino)-pyrimidin-4-yl]-3H-thiazol-2-one, with anticancer activity in animal models. PMID- 21035733 TI - Staphylococcus aureus and Bacillus subtilis W23 make polyribitol wall teichoic acids using different enzymatic pathways. AB - Wall teichoic acids (WTAs) are anionic polymers that play key roles in bacterial cell shape, cell division, envelope integrity, biofilm formation, and pathogenesis. B. subtilis W23 and S. aureus both make polyribitol-phosphate (RboP) WTAs and contain similar sets of biosynthetic genes. We use in vitro reconstitution combined with genetics to show that the pathways for WTA biosynthesis in B. subtilis W23 and S. aureus are different. S. aureus requires a glycerol-phosphate primase called TarF in order to make RboP-WTAs; B. subtilis W23 contains a TarF homolog, but this enzyme makes glycerol-phosphate polymers and is not involved in RboP-WTA synthesis. Instead, B. subtilis TarK functions in place of TarF to prime the WTA intermediate for chain extension by TarL. This work highlights the enzymatic diversity of the poorly characterized family of phosphotransferases involved in WTA biosynthesis in Gram-positive organisms. PMID- 21035735 TI - Metabolomics of Mycobacterium tuberculosis reveals compartmentalized co catabolism of carbon substrates. AB - Metabolic adaptation to the host environment is a defining feature of the pathogenicity of Mycobacterium tuberculosis (Mtb), but we lack biochemical knowledge of its metabolic networks. Many bacteria use catabolite repression as a regulatory mechanism to maximize growth by consuming individual carbon substrates in a preferred sequence and growing with diauxic kinetics. Surprisingly, untargeted metabolite profiling of Mtb growing on 13C-labeled carbon substrates revealed that Mtb could catabolize multiple carbon sources simultaneously to achieve enhanced monophasic growth. Moreover, when co-catabolizing multiple carbon sources, Mtb differentially catabolized each carbon source through the glycolytic, pentose phosphate, and/or tricarboxylic acid pathways to distinct metabolic fates. This unusual topologic organization of bacterial intermediary metabolism has not been previously observed and may subserve the pathogenicity of Mtb. PMID- 21035736 TI - hCB2 ligand-interaction landscape: cysteine residues critical to biarylpyrazole antagonist binding motif and receptor modulation. AB - The human cannabinoid 2 GPCR (hCB2) is a prime therapeutic target. To define potential cysteine-related binding motifs critical to hCB2-ligand interaction, a library of hCB2 cysteine-substitution mutants and a novel, high-affinity biarylpyrazole hCB2 antagonist/inverse agonist (AM1336) functionalized to serve as a covalent affinity probe to target cysteine residues within (or in the microenvironment of) its hCB2 binding pocket were generated. The data provide direct experimental demonstration that both hCB2 TMH7 cysteines [i.e., C7.38(284) and C7.42(288)] are critical to optimal hCB2-AM1336 binding interaction and AM1336 pharmacological activity in a cell-based functional assay (cAMP formation). Elongating the AM1336 aliphatic side chain generated another novel hCB2 inverse agonist that binds covalently and selectively to C7.42(288) only. Identification of specific cysteine residues critical to hCB2 ligand interaction and function informs the structure-based design of hCB2-targeted medicines. PMID- 21035737 TI - Fluorescent probes of tissue transglutaminase reveal its association with arterial stiffening. AB - Tissue transglutaminase (TG2) catalyzes the crosslinking of proteins. TG2 has been implicated in fibrosis and vascular calcification, both of which lead to a common feature of aging known as arterial stiffness. In order to probe the role of TG2 in arterial rigidification, we have prepared a fluorescent irreversible inhibitor as a probe for TG2 activity (RhodB-PGG-K(Acr)-LPF-OH). This probe was synthesized on solid support, characterized kinetically (k(inact) = 0.68 min-1, K(I) = 79 MUM), and then used to stain the aorta from rats used as a model of isolated systolic hypertension (ISH). Interestingly, TG2 activity was thus shown to increase over 4 weeks of the hypertension model, corresponding with the previously observed increase in arterial stiffness. These results clearly suggest an association between TG2 and the phenomenon of arterial rigidification. PMID- 21035738 TI - Effect of bioengineering lacticin 3147 lanthionine bridges on specific activity and resistance to heat and proteases. AB - Lacticin 3147 is a lantibiotic with seven lanthionine bridges across its two component peptides, Ltnalpha and Ltnbeta. Although it has been proposed that the eponymous lanthionine and (beta-methyl)lanthionine (Lan and meLan) bridges present in lantibiotics make an important contribution to protecting the peptides from thermal or proteolytic degradation, few studies have investigated this link. We have generated a bank of bioengineered derivatives of lacticin 3147, in which selected bridges were removed or converted between Lan and meLan, which were exposed to high temperature or proteolytic enzymes. Although switching Lan and meLan bridges has variable consequences, it was consistently observed that an intact N-terminal lanthionine bridge (Ring A) confers Ltnalpha with enhanced resistance to thermal and proteolytic degradation. PMID- 21035739 TI - Some colleagues in clinical practice hold the view that the contents of many "research journals" are of limited interest for them. Editorial. PMID- 21035740 TI - Electrode montages for tDCS and weak transcranial electrical stimulation: role of "return" electrode's position and size. PMID- 21035741 TI - A pilot study to determine whether machine learning methodologies using pre treatment electroencephalography can predict the symptomatic response to clozapine therapy. AB - OBJECTIVE: To investigate whether applying advanced machine learning (ML) methodologies to pre-treatment electroencephalography (EEG) data can predict the response to clozapine therapy in adult subjects suffering from chronic schizophrenia. METHODS: Pre-treatment EEG data are collected in 23+14 schizophrenic adults. Treatment outcome, after at least one year follow-up, is determined using clinical ratings by a trained clinician blind to EEG results. First, a feature selection scheme is employed to select a reduced subset of features extracted from the subjects' EEG that is most statistically relevant to our treatment-response prediction. These features are then entered into a classifier, which is realized in the form of a kernel partial least squares regression method that performs response prediction. Various scales, including the positive and negative syndrome scale (PANSS) are used as treatment-response indicators. RESULTS: We determined that a set of discriminating EEG features do exist. A low-dimensional representation of the feature space showed significant clustering into clozapine responder and non-responder groups. The minimum level of performance of the proposed prediction methodology, tested over a range of conditions using the leave-one-out cross-validation method using the original 23 subjects, with further testing in an independent sample of 14 subjects, was 85%. CONCLUSIONS: These findings indicate that analysis of pre-treatment EEG data can predict the clinical response to clozapine in treatment resistant schizophrenia. SIGNIFICANCE: If replicated in a larger population, this novel approach to EEG analysis may assist the clinician in determining treatment-efficacy. PMID- 21035742 TI - Transient and steady-state responses to mechanical stimulation of different fingers reveal interactions based on lateral inhibition. AB - OBJECTIVE: Simultaneous tactile finger stimulation evokes transient ERP responses that are smaller than the linear summation of ERP responses to individual stimulation. Occlusion and lateral inhibition are two possible mechanisms responsible for this effect. The present study disentangles these two effects using steady-state somatosensory evoked potentials (SSSEP). Simultaneous stimulation on adjacent and distant finger pairs with the same and different stimulation frequencies are compared. METHODS: The index finger (IF), middle finger (MF) and little finger (LF) were mechanically stimulated with a frequency of 18, 22 or 26Hz, respectively. Stimulation was applied for each finger separately, and for the IF (18Hz) in combination with either the MF or LF for 22 and 26Hz, respectively. A measure for interaction (IR) was calculated for the P60 component and the SSSEP amplitude. RESULTS: Significant interactions were found in both the P60 response and in the SSSEP response. Stimulation of adjacent finger combinations caused more interaction than distant finger combinations. No difference was found between stimulation of two fingers with the same or a different frequency. CONCLUSIONS: Our results indicate that lateral inhibition is mainly responsible for the interaction effect. SIGNIFICANCE: These observations provide further insight in the mechanisms behind interaction between somatosensory inputs. PMID- 21035743 TI - Frequency-dependent conduction block in ulnar neuropathy localized to the elbow. AB - OBJECTIVE: To determine whether frequency-dependent conduction block (FDB) occurs in acute ulnar neuropathies localized to the elbow. METHODS: High-frequency nerve stimulation (30Hz, 20 stimuli) was applied to the ulnar motor nerve above and below the elbow in controls (15) and in patients with short duration (between 2 and 16 weeks) ulnar neuropathy localized to the elbow (10) with evidence of moderate to severe conduction block and slowing. RESULTS: FDB was not observed in any of the 10 subjects tested. Three of these subjects were seen in follow-up; studies in two of these subjects, during the recovery period, did however demonstrate FDB with a similar pattern to that observed previously in CTS. CONCLUSIONS: This study has demonstrated that the remaining unblocked ulnar motor fibers across the elbow in acute ulnar neuropathy with conduction block, do not demonstrate FDB in response to stimulation at 30Hz. SIGNIFICANCE: These results suggest that FDB may not occur in the unblocked fibers in ulnar neuropathy despite evidence of conduction slowing. These results differ from previous observations in CTS and imply that demyelinating lesions (conduction block versus slowing) respond differently to high-frequency stimulation. PMID- 21035744 TI - Endorsement of the drug evaluation and classification program. PMID- 21035745 TI - Choose prevention. PMID- 21035746 TI - Validity of the VERA visual skills screening. AB - PURPOSE: Most school vision screenings test only visual acuity. There is a need for a valid, easily administered test that screens for a wider variety of learning-related vision problems. Visual Efficiency RAting (VERA) is a software program designed for schools to detect both routine vision problems and visual skill problems. The purpose of this study was to compare the VERA visual skills screening with the optometric assessment of binocular, accommodative, and ocular motor skills. METHODS: One hundred fifty-four children from grades 3 through 5 were evaluated using the VERA visual skills screening, a clinical battery of visual skills testing, the Convergence Insufficiency Symptom Survey, and 2 reading tests. RESULTS: The sensitivity of VERA in detecting visual skills problems was 45%, and the specificity was 83%. Sensitivity increased to 64% and specificity to 100% in smaller groups of children when overlays of symptoms, classroom behaviors, and reading skills were included. CONCLUSIONS: VERA has fairly good sensitivity and very good specificity in detecting visual skills problems. Given that the majority of visual skill deficits currently go undetected, VERA can be considered a reasonably effective method of in-school visual skills screening. PMID- 21035747 TI - Two presentations of nonarteritic ischemic optic neuropathy. AB - BACKGROUND: Nonarteritic ischemic optic neuropathy (NAION) is the most common acute optic neuropathy in adults over the age of 50. Patients affected notice sudden and painless loss of vision in 1 eye, often upon awaking. Studies have found that the opposite eye may be affected in approximately 15% to 20% of cases within a 5-year period. NAION vision loss results from an ischemic event often affecting the short posterior ciliary arteries. This results in optic nerve pallor, nerve fiber layer defects, and corresponding visual field defects. CASE REPORTS: Two cases of NAION are discussed here. The first patient, a 57-year-old woman, had a 10-year history of visual symptoms, and the second, a 66-year-old man, presented in less than a week after first noticing symptoms. Both had predisposing systemic risk factors and resultant visual field loss and decreased visual acuity. CONCLUSIONS: Predisposing factors for NAION include small cup-to disc ratios of the optic nerve, obstructive sleep apnea, nocturnal hypotension, diabetes, and other vascular diseases. The vision loss is irreversible, and there is no known effective treatment to prevent subsequent disc atrophy or recurring episodes. PMID- 21035748 TI - Compliance with soft contact lens replacement schedules and associated contact lens-related ocular complications: the UCLA Contact Lens Study. AB - BACKGROUND: Failure to comply with the manufacturers' recommended replacement frequency (MRRF) is expected to result in ocular complications. The goal of this study is to evaluate the empirical relationship between compliance with MRRF and the presence of ocular complications. METHODS: All soft contact lens-wearing patients who presented at either of 2 clinics were evaluated prospectively for contact lens-related complications and for compliance with MRRF. RESULTS: Compliance with MRRF varies significantly across replacement modality (P < 0.01) and lens solution type (P = 0.04). Among noncompliant patients, average days of overwear beyond MRRF significantly varies across age group (P = 0.02), lens material type (P = 0.01), and lens solution type (P = 0.02). Regression analysis controlling for demographic factors and lens and solution type found a marginally significant (P = 0.07) positive effect of days of overwear on average complications per eye. CONCLUSIONS: We find noncompliance broadly present across demographic groups and patient types and marginally positively related to complications. PMID- 21035749 TI - TRPV1, hypertension, and cardiovascular regulation. PMID- 21035751 TI - Divergent effects of central and peripheral renin on body weight and metabolism. AB - Renin regulates blood pressure and fluid volume. In this issue of Cell Metabolism, Grobe et al. (2010) provide convincing evidence for a new role for brain renin in metabolic rate and weight loss. Renin overexpression or deletion peripherally from other studies suggests the opposite effect. PMID- 21035752 TI - Megarole for microRNA in muscle disease. AB - Deregulation of microRNAs in dystrophic muscle highlights their importance in muscle homeostasis. A recent study in Cell Metabolism (Cacchiarelli et al., 2010) shows that the presence of functional dystrophin is required for NO-dependent nitrosylation of the HDAC2 repressor and subsequent activation of a group of microRNAs required for muscle function. PMID- 21035753 TI - IL-1beta activation as a response to metabolic disturbances. AB - IL-1beta is a major regulator of islet inflammation in type 2 diabetes. Several factors contribute to the induction of islet-derived IL-1beta, including glucose, free fatty acids, and leptin. A recent report in Nature Immunology (Masters et al., 2010) identifies amyloid polypeptide as an additional enhancer of IL-1beta production. PMID- 21035754 TI - Allosteric trumps covalent in the control of glycogen synthesis. AB - Glycogen metabolism serves as a critical regulator of energy storage and maintenance of blood glucose levels in a physiological range. In this issue of Cell Metabolism, Bouskila et al. (2010) unexpectedly find that skeletal muscle glycogen accumulation is principally controlled by the allosteric activation of glycogen synthase, opening new avenues for investigation. PMID- 21035755 TI - The brain Renin-angiotensin system controls divergent efferent mechanisms to regulate fluid and energy balance. AB - The renin-angiotensin system (RAS), in addition to its endocrine functions, plays a role within individual tissues such as the brain. The brain RAS is thought to control blood pressure through effects on fluid intake, vasopressin release, and sympathetic nerve activity (SNA), and may regulate metabolism through mechanisms which remain undefined. We used a double-transgenic mouse model that exhibits brain-specific RAS activity to examine mechanisms contributing to fluid and energy homeostasis. The mice exhibit high fluid turnover through increased adrenal steroids, which is corrected by adrenalectomy and attenuated by mineralocorticoid receptor blockade. They are also hyperphagic but lean because of a marked increase in body temperature and metabolic rate, mediated by increased SNA and suppression of the circulating RAS. beta-adrenergic blockade or restoration of circulating angiotensin-II, but not adrenalectomy, normalized metabolic rate. Our data point to contrasting mechanisms by which the brain RAS regulates fluid intake and energy expenditure. PMID- 21035756 TI - Global epigenomic analysis of primary human pancreatic islets provides insights into type 2 diabetes susceptibility loci. AB - Identifying cis-regulatory elements is important to understanding how human pancreatic islets modulate gene expression in physiologic or pathophysiologic (e.g., diabetic) conditions. We conducted genome-wide analysis of DNase I hypersensitive sites, histone H3 lysine methylation modifications (K4me1, K4me3, K79me2), and CCCTC factor (CTCF) binding in human islets. This identified ~18,000 putative promoters (several hundred unannotated and islet-active). Surprisingly, active promoter modifications were absent at genes encoding islet-specific hormones, suggesting a distinct regulatory mechanism. Of 34,039 distal (nonpromoter) regulatory elements, 47% are islet unique and 22% are CTCF bound. In the 18 type 2 diabetes (T2D)-associated loci, we identified 118 putative regulatory elements and confirmed enhancer activity for 12 of 33 tested. Among six regulatory elements harboring T2D-associated variants, two exhibit significant allele-specific differences in activity. These findings present a global snapshot of the human islet epigenome and should provide functional context for noncoding variants emerging from genetic studies of T2D and other islet disorders. PMID- 21035757 TI - Allosteric regulation of glycogen synthase controls glycogen synthesis in muscle. AB - Glycogen synthase (GS), a key enzyme in glycogen synthesis, is activated by the allosteric stimulator glucose-6-phosphate (G6P) and by dephosphorylation through inactivation of GS kinase-3 with insulin. The relative importance of these two regulatory mechanisms in controlling GS is not established, mainly due to the complex interplay between multiple phosphorylation sites and allosteric effectors. Here we identify a residue that plays an important role in the allosteric activation of GS by G6P. We generated knockin mice in which wild-type muscle GS was replaced by a mutant that could not be activated by G6P but could still be activated normally by dephosphorylation. We demonstrate that knockin mice expressing the G6P-insensitive mutant display an ~80% reduced muscle glycogen synthesis by insulin and markedly reduced glycogen levels. Our study provides genetic evidence that allosteric activation of GS is the primary mechanism by which insulin promotes muscle glycogen accumulation in vivo. PMID- 21035758 TI - Atherogenic lipids and lipoproteins trigger CD36-TLR2-dependent apoptosis in macrophages undergoing endoplasmic reticulum stress. AB - Macrophage apoptosis in advanced atheromata, a key process in plaque necrosis, involves the combination of ER stress with other proapoptotic stimuli. We show here that oxidized phospholipids, oxidized LDL, saturated fatty acids (SFAs), and lipoprotein(a) trigger apoptosis in ER-stressed macrophages through a mechanism requiring both CD36 and Toll-like receptor 2 (TLR2). In vivo, macrophage apoptosis was induced in SFA-fed, ER-stressed wild-type but not Cd36-(/)- or Tlr2 (/)- mice. For atherosclerosis, we combined TLR2 deficiency with that of TLR4, which can also promote apoptosis in ER-stressed macrophages. Advanced lesions of fat-fed Ldlr-(/)- mice transplanted with Tlr4-(/)-Tlr2-(/)- bone marrow were markedly protected from macrophage apoptosis and plaque necrosis compared with WT ->Ldlr-(/)- lesions. These findings provide insight into how atherogenic lipoproteins trigger macrophage apoptosis in the setting of ER stress and how TLR activation might promote macrophage apoptosis and plaque necrosis in advanced atherosclerosis. PMID- 21035759 TI - A liver-derived secretory protein, selenoprotein P, causes insulin resistance. AB - The liver may regulate glucose homeostasis by modulating the sensitivity/resistance of peripheral tissues to insulin, by way of the production of secretory proteins, termed hepatokines. Here, we demonstrate that selenoprotein P (SeP), a liver-derived secretory protein, causes insulin resistance. Using serial analysis of gene expression (SAGE) and DNA chip methods, we found that hepatic SeP mRNA levels correlated with insulin resistance in humans. Administration of purified SeP impaired insulin signaling and dysregulated glucose metabolism in both hepatocytes and myocytes. Conversely, both genetic deletion and RNA interference-mediated knockdown of SeP improved systemic insulin sensitivity and glucose tolerance in mice. The metabolic actions of SeP were mediated, at least partly, by inactivation of adenosine monophosphate activated protein kinase (AMPK). In summary, these results demonstrate a role of SeP in the regulation of glucose metabolism and insulin sensitivity and suggest that SeP may be a therapeutic target for type 2 diabetes. PMID- 21035760 TI - The transcriptional coregulators TIF2 and SRC-1 regulate energy homeostasis by modulating mitochondrial respiration in skeletal muscles. AB - The two p160 transcriptional coregulator family members SRC-1 and TIF2 have important metabolic functions in white and brown adipose tissues as well as in the liver. To analyze TIF2 cell-autonomous functions in skeletal muscles, we generated TIF2((i)skm)-(/)- mice in which TIF2 was selectively ablated in skeletal muscle myofibers at adulthood. We found that increased mitochondrial uncoupling in skeletal muscle myocytes protected these mice from decreased muscle oxidative capacities induced by sedentariness, delayed the development of type 2 diabetes, and attenuated high-caloric-diet-induced obesity. Moreover, our results demonstrate that SRC-1 and TIF2 can modulate the expression of the uncoupling protein 3 (UCP3) in an antagonistic manner and that enhanced SRC-1 levels in TIF2 deficient myofibers are critically involved in the metabolic changes of TIF2((i)skm)-(/)- mice. Thus, modulation of the expression and/or activity of these coregulators represents an attractive way to prevent or treat metabolic disorders. PMID- 21035762 TI - PERILIPIN-dependent control of lipid droplet structure and fat storage in Drosophila. AB - Lipid droplets are intracellular organelles enriched in adipose tissue that govern the body fat stores of animals. In mammals, members of the evolutionarily conserved PERILIPIN protein family are associated with the lipid droplet surface and participate in lipid homeostasis. Here, we show that Drosophila mutants lacking the PERILIPIN PLIN1 are hyperphagic and suffer from adult-onset obesity. PLIN1 is a central and Janus-faced component of fat metabolism. It provides barrier function to storage lipid breakdown and acts as a key factor of stimulated lipolysis by modulating the access of proteins to the lipid droplet surface. It also shapes lipid droplet structure, transforming unilocular into multilocular fat cells. We generated flies devoid of all PERILIPIN family members and show that they exhibit impaired yet functional body fat regulation. Our data reveal the existence of a basal and possibly ancient lipid homeostasis system. PMID- 21035761 TI - PER2 controls lipid metabolism by direct regulation of PPARgamma. AB - Accumulating evidence highlights intriguing interplays between circadian and metabolic pathways. We show that PER2 directly and specifically represses PPARgamma, a nuclear receptor critical in adipogenesis, insulin sensitivity, and inflammatory response. PER2-deficient mice display altered lipid metabolism with drastic reduction of total triacylglycerol and nonesterified fatty acids. PER2 exerts its inhibitory function by blocking PPARgamma recruitment to target promoters and thereby transcriptional activation. Whole-genome microarray profiling demonstrates that PER2 dictates the specificity of PPARgamma transcriptional activity. Indeed, lack of PER2 results in enhanced adipocyte differentiation of cultured fibroblasts. PER2 targets S112 in PPARgamma, a residue whose mutation has been associated with altered lipid metabolism. Lipidomic profiling demonstrates that PER2 is necessary for normal lipid metabolism in white adipocyte tissue. Our findings support a scenario in which PER2 controls the proadipogenic activity of PPARgamma by operating as its natural modulator, thereby revealing potential avenues of pharmacological and therapeutic intervention. PMID- 21035763 TI - High-fat-diet-induced obesity and heart dysfunction are regulated by the TOR pathway in Drosophila. AB - High-fat-diet (HFD)-induced obesity is a major contributor to diabetes and cardiovascular disease, but the underlying genetic mechanisms are poorly understood. Here, we use Drosophila to test the hypothesis that HFD-induced obesity and associated cardiac complications have early evolutionary origins involving nutrient-sensing signal transduction pathways. We find that HFD-fed flies exhibit increased triglyceride (TG) fat and alterations in insulin/glucose homeostasis, similar to mammalian responses. A HFD also causes cardiac lipid accumulation, reduced cardiac contractility, conduction blocks, and severe structural pathologies, reminiscent of diabetic cardiomyopathies. Remarkably, these metabolic and cardiotoxic phenotypes elicited by HFD are blocked by inhibiting insulin-TOR signaling. Moreover, reducing insulin-TOR activity (by expressing TSC1-2, 4EBP or FOXO), or increasing lipase expression-only within the myocardium-suffices to efficiently alleviate cardiac fat accumulation and dysfunction induced by HFD. We conclude that deregulation of insulin-TOR signaling due to a HFD is responsible for mediating the detrimental effects on metabolism and heart function. PMID- 21035764 TI - Glucose stimulation of hypothalamic MCH neurons involves K(ATP) channels, is modulated by UCP2, and regulates peripheral glucose homeostasis. AB - Blood glucose levels are tightly controlled, a process thought to be orchestrated primarily by peripheral mechanisms (insulin secretion by beta cells, and insulin action on muscle, fat, and liver). The brain also plays an important, albeit less well-defined role. Subsets of neurons in the brain are excited by glucose; in many cases this involves ATP-mediated closure of K(ATP) channels. To understand the relevance of this, we are manipulating glucose sensing within glucose-excited neurons. In the present study, we demonstrate that glucose excitation of MCH expressing neurons in the lateral hypothalamus is mediated by K(ATP) channels and is negatively regulated by UCP2 (a mitochondrial protein that reduces ATP production), and that glucose sensing by MCH neurons plays an important role in regulating glucose homeostasis. Combined, the glucose-excited neurons are likely to play key, previously unexpected roles in regulating blood glucose. PMID- 21035765 TI - Action of student-resident interaction during a surgical clerkship. AB - BACKGROUND: This study is a qualitative assessment of the effect of clinical encounter documentation cards on medical student-surgical resident interaction during the core surgical clerkship, junior medical school year. METHODOLOGY: The implementation of a clinical encounter documentation card system occurred during academic year 2009-2010. The results were compared with historical control medical student cohorts from antecedent academic years. The perceptions of overall quality of the clerkship and effectiveness of residents as teachers were assessed using a psychometric Likert scale. RESULTS: Ninety percent of the medical students and surgical residents "agreed" or "strongly agreed" that the educational value of clinical encounters was enhanced by the documentation card system. DISCUSSION: Junior medical students receive a substantial and valuable portion of their formal surgical education from surgical residents. We argue that this documentation card system tangibly increased the educational value of clinical encounters and improved the cognitive, technical, and rhetorical skills of both medical students and surgical residents. CONCLUSION: We submit that this clinical encounter documentation card system: improved each student's educational experience and each resident's teaching ability; provided valuable information about residents as teachers; facilitated more refined assessment of their performance in relationship to the core competencies; provided timely information permitting adjustments of clinical service assignments during each rotation; and "clinical context teaching moments" were perceived as a valuable element of the core surgical clerkship. PMID- 21035766 TI - Evidence-based surgery: knowledge, attitudes, and perceived barriers among surgical trainees. AB - OBJECTIVES: This study was conducted to assess the knowledge and attitude of surgical trainees toward evidence-based medicine (EBM) and their perceived barriers to its practice. DESIGN: The McColl questionnaire and the BARRIERS scale were modified and incorporated into a single questionnaire, which was administered to all surgical trainees attending a Continuing Surgical Education meeting. SETTING: Department of Surgery, Christian Medical College, Vellore, India. PARTICIPANTS: One hundred ten surgical trainees from 22 medical colleges. RESULTS: In all, 84.5% (93/110) trainees returned the questionnaire. The attitudes toward EBM were welcoming, although individual participants reported they welcomed EBM more than their colleagues did. Participants agreed that EBM was useful in everyday practice and that it improved patient care. About 50% of actual practice was considered evidence based. In all, 12.6% (10/89) of participants had received formal training in EBM, and 64.3% (54/84) of participants were aware of the Cochrane database of systemic reviews, but only 35.7% (30/84) read it regularly. Also, 67.8% (61/90) of respondents used protocols and guidelines developed by colleagues. However, 61.5% (56/91) of participants were interested in learning the skills of EBM. The terms absolute risk, relative risk, and clinical effectiveness were understood by >80% of respondents, whereas publication bias, confidence interval, and heterogeneity were poorly understood. The major barriers to practice of EBM were the inability to understand statistical analysis, inadequate facilities for implementation, lack of a single compiled source of literature, relevant literature not being readily available, and insufficient time on the job. CONCLUSIONS: Surgical trainees have a positive attitude towards EBM and have some familiarity with the common terms used in EBM. There is a need to increase awareness of, and provide access to, available sources of medical literature. Formal training in EBM, as well as basic statistical analysis, should form a part of the surgical curriculum to foster an environment favorable to the practice of EBM. PMID- 21035767 TI - Impact of the 80-hour workweek on surgical case exposure within a general surgery residency program. AB - OBJECTIVE: The objective of this statistical analysis was to test the hypothesis that implementation of the 80-hour workweek restrictions for General Surgery residents at Riverside Methodist Hospital after July 2003 decreased their operative experience relative to surgical residents trained at Riverside before these changes. DESIGN, SETTING, PARTICIPANTS: Data were collected from the Accreditation Council for Graduate Medical Education national database and from Riverside Methodist Hospital's General Surgery Residency records for a sampling of academic years before and after the duty-hour changes in surgical education (July 1, 2003). Current procedural terminology (CPT) surgical procedure codes logged by postgraduate year (PGY) 5 General Surgery residents 15 years before and 5 years after implementation of the 80-hour workweek were compared. The outcome variables "total major cases" and "Chief cases" were compared between 2 study groups defined by the time intervals exclusively before July 2003 ("pre") and inclusively after July 2003 ("post"). Hospital general surgical case volume for the study intervals was also tallied. Statistical analyses included 1- and 2 sided t-tests, nonparametric tests, and t-tests on a 3-parameter logarithmic transformation of the data. RESULTS: Despite an upward trend in total general surgery cases (slope = 25/year, p = 0.005), there was a statistically significant decrease in the operative experience for categorical surgical residents following the 80-hour workweek restrictions. The mean (SD) number of major cases performed by "pre"-restriction residents during their training significantly exceeded that of their "post" cohorts (1395 [326] vs 953 [134], p < 0.001). The training for PGY 5 residents was similarly influenced (345 [81] vs 237 [55], p < .0001). CONCLUSIONS: Despite an increase in the total number of major operative cases available, the volume of cases performed by residents has decreased after implementation of the Accreditation Council for Graduate Medical Education (ACGME) work-hour restrictions. Our data suggest that the impact of the 80-hour workweek has had a detrimental effect on the conventional resident training experience. PMID- 21035768 TI - Improving education under work-hour restrictions: comparing learning and teaching preferences of faculty, residents, and students. AB - BACKGROUND: Faced with work-hour restrictions, educators are mandated to improve the efficiency of resident and medical student education. Few studies have assessed learning styles in medicine; none have compared teaching and learning preferences. Validated tools exist to study these deficiencies. Kolb describes 4 learning styles: converging (practical), diverging (imaginative), assimilating (inductive), and accommodating (active). Grasha Teaching Styles are categorized into "clusters": 1 (teacher-centered, knowledge acquisition), 2 (teacher centered, role modeling), 3 (student-centered, problem-solving), and 4 (student centered, facilitative). STUDY DESIGN: Kolb's Learning Style Inventory (HayGroup, Philadelphia, Pennsylvania) and Grasha-Riechmann's TSS were administered to surgical faculty (n = 61), residents (n = 96), and medical students (n = 183) at a tertiary academic medical center, after informed consent was obtained (IRB # 06 0612). Statistical analysis was performed using chi(2) and Fisher exact tests. RESULTS: Surgical residents preferred active learning (p = 0.053), whereas faculty preferred reflective learning (p < 0.01). As a result of a comparison of teaching preferences, although both groups preferred student-centered, facilitative teaching, faculty preferred teacher-centered, role-modeling instruction (p = 0.02) more often. Residents had no dominant teaching style more often than surgical faculty (p = 0.01). Medical students preferred converging learning (42%) and cluster 4 teaching (35%). Statistical significance was unchanged when corrected for gender, resident training level, and subspecialization. CONCLUSIONS: Significant differences exist between faculty and residents in both learning and teaching preferences; this finding suggests inefficiency in resident education, as previous research suggests that learning styles parallel teaching styles. Absence of a predominant teaching style in residents suggests these individuals are learning to be teachers. The adaptation of faculty teaching methods to account for variations in resident learning styles may promote a better learning environment and more efficient faculty-resident interaction. Additional, multi-institutional studies using these tools are needed to elucidate these findings fully. PMID- 21035769 TI - Knowledge, attitudes, and practices (KAP) survey based on two pilot-tested, self administered questionnaires administered to consenting faculty and resident participants and retrieved in a sealed, anonymized envelope. AB - BACKGROUND: Various socioeconomic changes are driving a review of surgical resident training. Concern exists that these demands are not well perceived by surgical faculty thereby leading to a hiatus between how surgical residents are educated and what is expected of them as independent clinicians. It is necessary to quantify resident and faculty awareness of these issues and to find areas of improvement for making resident education more relevant to this changing socioeconomic setup. OBJECTIVES: 1. To gauge awareness among surgical faculty and residents in regard to trends and concepts in postgraduate surgical education. 2. To compare how the attitudes and practices differ among the faculty and residents vis-a-vis resident education. SETTING: Aga Khan University Hospital, Karachi, a tertiary care, private teaching hospital in Pakistan. RESULTS: With a retrieval rate of 70% for the faculty and 90% for the residents, the survey revealed interesting differences in perceptions between the 2 groups. Knowledge among respondents is very good for certain aspects of adult education, whereas other areas leave room for improvement. Faculty and residents have opposing views on resident work-hour reduction. Faculty overestimate their roles as enablers. Good knowledge about motivations for adult learning is not translated into positive attitudes and humiliation remains prevalent as does indifference toward imbibing advances into resident education. Residents generally were dissatisfied about their operative experience. CONCLUSIONS: A gap persists in knowledge about motivations for resident learning and practices. Implementation of a skills laboratory curriculum, objective-oriented rotations, and interdisciplinary initiatives for imbibing advances are potential avenues for improvement. PMID- 21035770 TI - Medical students and general surgery--Israel's National Survey: lifestyle is not the sole issue. AB - BACKGROUND: In recent years, a significant decline in the number of medical school graduates who choose general surgery as a career has been noted in Israel. The aim of this study is to characterize the factors that deter Israeli medical students from choosing general surgery. Previous studies in the United States identified lifestyle and financial issues as the most important factors. METHODS: A web-based survey was distributed to graduating medical students throughout Israel. The survey covered different factors and aspects affecting career choice, requiring participants to rate their choices with a 1-5 score. RESULTS: In all, 218 surveys were completed; 72 (33%) students considered general surgery before the surgical clerkship versus only 48 (22%) students after. Professional interest and satisfaction (4.7) were ranked as the most important factors for choosing a residency, followed by an amiable working atmosphere (4.3). The 2 strongest deterrents from general surgery were doctors' inter-relationships (3.5) and compromised lifestyle (3.3). The decision to avoid surgery can be reversed by improving both lifestyle (3.5) and inter-relationships (3.0), but it is less influenced by a substantial increase in residents' salary. CONCLUSIONS: More medical graduates would consider general surgery as a career option if the lifestyle and inter-relationships were perceived as better. An increase in monetary reward did not seem to have a paramount impact among Israeli medical graduates. The surgical clerkship is an important turning point in the students' attitude toward surgery as a career and efforts must be made to improve students' experience significantly during this clerkship. PMID- 21035771 TI - The development of a comprehensive school-wide simulation-based procedural skills curriculum for medical students. AB - OBJECTIVE: The purpose of this project was to assess the effectiveness of using the Delphi process to create a structured simulation-based procedural skills curriculum for all students at the Keck School of Medicine of the University of Southern California (KSOM). METHODS: The Delphi process was used to develop a list of procedural skills that students are expected to perform competently prior to graduation. Once consensus of faculty was reached, a needs assessment was performed to poll graduating seniors' experience performing each skill. A comprehensive simulation-based curriculum was developed and implemented for all Year II students at KSOM. Student satisfaction with the curriculum was collected using a standardized end-of-session evaluation form and student self confidence was assessed using a retrospective pre- and post-self-efficacy rating for each skill. RESULTS: The needs assessment clearly established the need for a more organized approach to teaching procedural skills at KSOM. Quantitative and qualitative data revealed that students responded favorably to the curriculum and appreciated the efforts put forth by KSOM. Student self-efficacy increased significantly for each skill. CONCLUSIONS: The Delphi process was effective in reaching consensus among educational leaders at KSOM regarding which skills to include in the curriculum. Although there were a few minor challenges, we determined that it is feasible to develop and implement an explicit school-wide simulated-based procedural skills curriculum. PMID- 21035772 TI - The impact of laparoscopy on the volume of open cases in general surgery training. AB - OBJECTIVE: The purpose of this study was to evaluate the impact of laparoscopy on the volume of open cases in general surgery residency training over the past 10 years. DESIGN: The Accreditation Council for Graduate Medical Education (ACGME) database (1999-2008), which records all cases (by Current Procedural Terminology code) performed by graduating general surgery trainees, was retrospectively analyzed. SETTING: ACGME database (1999-2008). MAIN OUTCOME MEASURES: Trends were compared regarding the average number of the most common laparoscopic and open procedures (colectomy, hernia, and appendectomy) performed by graduating general surgery trainees during the reporting period. RESULTS: Across all procedures, an increase was noted in laparoscopic approaches with a reciprocal decrease in open cases. The number of open appendectomies decreased by 29% (30.7 to 21.7), whereas the number of laparoscopic appendectomies increased by 278% (8.5 to 32.1). Similarly, open inguinal hernia cases decreased by 12.5% (51.9 to 45.4) and open colectomy cases decreased by 10.4% (48 to 43). Conversely, laparoscopic hernia repair and laparoscopic colectomy increased by 87.5% (7.6 to 15.8) and 550% (2 to 13), respectively. CONCLUSIONS: In addition to the limitations placed on residency training by other factors (including work hour restrictions), changing practice patterns within the field of general surgery have a significant impact on the exposure of residents to open surgery cases. This trend might have far reaching implications with regard to the overall competency of graduating residents and raises concerns for the future direction of surgical education. PMID- 21035773 TI - The influence of surgical demonstrations during an anatomy course on the perceptions of first-year medical students toward surgeons and a surgical career. AB - OBJECTIVE: We previously have demonstrated the educational benefits of surgical demonstrations to first-year medical students. The aim of this current study was to analyze the influence of these demonstrations on the perceptions of students toward surgeons and a possible career in surgery. METHODS: A faculty member from the Department of Surgery provided an instruction on pancreatic malignancies and management to first-year medical students during their gross anatomy course. After this instruction, using a lightly embalmed cadaver, the clinically relevant anatomy was detailed and a pancreaticoduodenectomy was performed on the cadaver. Immediately after the demonstration, a brief survey was conducted to obtain feedback from the students about the experience. RESULTS: A total of 170 students over 2 years returned the survey for a response rate of 69%. The demonstration provided 77% of students with a favorable impression of surgeons, and 90% of the students felt that this exposure gave them an understanding of the knowledge, skills, and qualities needed to become a surgeon. Additionally, 57% of respondents stated that watching the demonstration increased the likelihood of them pursuing a surgical career. For the 67% of students who were considering a surgery career, the demonstration reinforced their interest; however, for the students who were not interested in surgery, the demonstration did not alter their opinion. CONCLUSION: The results of this study showed that surgical demonstrations to first-year medical students can influence their perceptions favorably about surgeons and a surgical career. This interaction provided students with information and motivation to pursue a career in surgery and also may counteract any negative stereotypes of the field that first-year students may have had. PMID- 21035774 TI - Thoracic surgery training in Canada according to the residents: the thoracic surgery resident survey, of the Canadian thoracic manpower and education study (T Med). AB - OBJECTIVE: The resident component of the Canadian Thoracic Manpower and Education Study (T-MED) was conducted to understand the basic demographic of Canadian thoracic surgery residents, the factors influencing their selection of training programs, current work conditions, training and competencies, and opinions in regard to the manpower needs for the specialty. DESIGN: A modified Delphi process was used to develop a survey applicable to thoracic surgery residents. In May and June 2009, residents completed the voluntary anonymous Internet-based survey. All Canadian residents participated in the survey, providing a 100% response rate. RESULTS: Most respondents were male (11/12), and the average age was 34 years old with an anticipated debt greater than $50,000 on graduation. All residents worked more than 70 hours per week, with most doing 1 : 3 or 1 : 4 on-call. Two-thirds of respondents reported being satisfied or very satisfied with their training program. Rates of anticipated competence in performing various thoracic surgeries on graduation differed between residents and program directors. Two-thirds (8/12) of residents planned to practice thoracic surgery exclusively, and hoped to practice in an academic setting. Most residents (10/12) agreed or strongly agreed that not enough jobs are available in Canada for graduating trainees and that the number of residency positions should reflect the predicted availability of jobs. CONCLUSIONS: This study has provided detailed information on thoracic surgery resident demographics and training programs. Most thoracic surgery residents are satisfied with their current training program but have concerns about their job prospects on graduation, and they believe that the number of training positions should reflect potential job opportunities. This survey represents the first attempt to characterize the current state of thoracic surgery training in Canada from the resident's perspective and may help in directing educational and manpower planning. PMID- 21035775 TI - Center for Simulation, Education and Research at Henry Ford hospital. PMID- 21035776 TI - Duke Surgical Education and Activities Laboratory and Comprehensive Education Institute. PMID- 21035777 TI - American College of Surgeons Comprehensive Education Institute: Hartford Hospital. PMID- 21035778 TI - The Center for Advanced Medical Simulation, Karolinska Institutet, Karolinska University Hospital, and Stockholm County Council. PMID- 21035779 TI - University of California, Irvine Education Institute. PMID- 21035780 TI - Attention and spatial stimulus coding in the Simon task: a rejoinder to van der Lubbe and Abrahamse (2010). AB - Hommel (2011-this issue) has reviewed the major lines of research and ongoing controversies on and around the Simon effect. Van der Lubbe and Abrahamse (2010) take issue with Hommel's assessment of the role of attention shifting in the Simon effect. This rejoinder argues that van der Lubbe and Abrahamse's criticism is off target because it (a) fails to distinguish between the attention-shifting account of (spatial stimulus coding in) the Simon effect-which Hommel discusses and criticizes-and the premotor theory of attention-which Hommel does not discuss; (b) confuses the relationship between the attention-shifting account and the referential-coding account of spatial stimulus coding in the Simon effect-the actual topic of Hommel's discussion-with the relationship between the premotor theory and the theory of event coding-which the criticism focuses on; and (c) confuses the uncontroversial role of attention in stimulus selection with the controversial role of attention in the generation of location codes. PMID- 21035781 TI - The levonorgestrel-releasing intrauterine system in human immunodeficiency virus infected women: a 5-year follow-up study. AB - OBJECTIVE: We sought to assess the effects of long-term use and safety of the levonorgestrel-releasing (LNG)-intrauterine system (IUS) among human immunodeficiency virus (HIV)-infected women in comparison with HIV-infected women not using the device. STUDY DESIGN: Fifteen women using the LNG-IUS and their 25 age- and CD4(+) lymphocyte count-matched control subjects with annual follow-up data were followed up for 5 years. RESULTS: No unplanned pregnancies or pelvic infections occurred among the LNG-IUS users. Altogether, 12 (80%) of the LNG-IUS users continued its use up to 5 years. Annual CD4(+) lymphocyte counts were similar in the LNG-IUS users and control subjects throughout the follow-up period. The hemoglobin levels increased initially (P < .005) and remained higher among the LNG-IUS users (P < .02). Pap smears displayed non-squamous intraepithelial lesion cytology in >= 85% of cases in both groups. CONCLUSION: No unfavorable effects on the course of HIV infection were noted during long-term use of the LNG-IUS. Dual protection by means of an LNG-IUS and condoms might be an ideal contraceptive strategy for HIV-infected women. PMID- 21035782 TI - BD Pharmingen purified mouse anti-cytokeratin 7 monoclonal antibody (clone RCK105) should not be mistaken for BD Biosciences anti-cytokeratin CAM5.2 reagent (clone CAM 5.2). PMID- 21035783 TI - Application of a digital head-posture measuring system in children. AB - PURPOSE: To report the repeatability of a digital head-posture measuring system when used to record anomalous head postures in children. DESIGN: Prospective study and clinical laboratory investigation. METHODS: Using a digital head posture measuring system, we measured 36 different anomalous head postures in 27 children with infantile nystagmus syndrome. Repeatability values and 95% limits of repeatability of measurements were generated for anomalous head postures. RESULTS: Among the 27 children, 3 had 2 head postures (right and left head turns) in 2 different directions; 6 had 2-dimensional head postures that were considered 2 different head postures; and 18 had a 1-dimensional head posture. There were 5 chin-up or chin-down postures, 23 head-turn postures, and 8 head-tilt postures in a total of 36 anomalous head postures. The repeatability value for all anomalous head postures was less than 10 degrees. Ninety-five percent limits of repeatability yielded ranges of less than 10 degrees for all anomalous head postures. CONCLUSIONS: The digital head-posture measuring system is a valid and reliable device for measuring 3-dimensional head postures in children with nystagmus. PMID- 21035784 TI - The influence of schizophrenia-related neuregulin-1 polymorphisms on sensorimotor gating in healthy males. AB - BACKGROUND: Neuregulin-1 (NRG1) variations have been shown to modulate schizophrenia candidate endophenotypes related to brain structure and function. The objective of this cross-sectional genetic association study was to determine the relationship of six core single-nucleotide polymorphisms within the NRG1 gene identified as promising schizophrenia risk genes (rs6994992, SNP8NRG221132, SNP8NRG241930, rs3924999, rs2439272 and rs10503929) to prepulse inhibition (PPI) of the acoustic startle reflex, a well validated schizophrenia endophenotype. METHODS: PPI was tested in a highly homogeneous study entry cohort (n = 445) of carefully screened healthy, young male army conscripts originating from the Greek LOGOS project (Learning on Genetics of Schizophrenia Spectrum). The QTPHASE from the UNPHASED package was used for the association analysis of each single nucleotide polymorphisms or haplotype data. RESULTS: Reduced PPI, particularly at 75-dB_120-msec and 85-dB_60-msec trials, was related to the SNP8NRG241930 G allele and especially the rs6994992 T allele and rs2439272 C allele. Haplotype analysis followed up by risk versus no-risk groups Analysis of variance confirmed that the rs10503929 and rs3924999 SNPs were also associated with PPI reductions, when combined with rs2439272. CONCLUSIONS: We provide solid evidence for a role of NRG1 risk genotype variations in PPI reductions in a large and demographically and genetically highly homogeneous cohort of healthy young males. These results further validate NRG1 as a candidate gene for the schizophrenia and spectrum disorders and improve our understanding of its functional mechanisms within the human brain because they suggest an influence of the gene in the neural substrate mediating sensorimotor gating. PMID- 21035785 TI - Altered medial temporal activation related to local glutamate levels in subjects with prodromal signs of psychosis. AB - BACKGROUND: Both medial temporal cortical dysfunction and perturbed glutamatergic neurotransmission are regarded as fundamental pathophysiological features of psychosis. However, although animal models of psychosis suggest that these two abnormalities are interrelated, their relationship in humans has yet to be investigated. METHODS: We used a combination of functional magnetic resonance imaging and magnetic resonance spectroscopy to investigate the relationship between medial temporal activation during an episodic memory task and local glutamate levels in 22 individuals with an at-risk mental state for psychosis and 14 healthy volunteers. RESULTS: We observed a significant between-group difference in the coupling of medial temporal activation with local glutamate levels. In control subjects, medial temporal activation during episodic encoding was positively associated with medial temporal glutamate. However, in the clinical population, medial temporal activation was reduced, and the relationship with glutamate was absent. CONCLUSIONS: In individuals at high risk of psychosis, medial temporal dysfunction seemed related to a loss of the normal relationship with local glutamate levels. This study provides the first evidence that links medial temporal dysfunction with the central glutamate system in humans and is consistent with evidence that drugs that modulate glutamatergic transmission might be useful in the treatment of psychosis. PMID- 21035786 TI - cAMP response element binding protein phosphorylation in nucleus accumbens underlies sustained recovery of sensorimotor gating following repeated D2-like receptor agonist treatment in rats. AB - BACKGROUND: Prepulse inhibition (PPI) is a cross-species measure of sensorimotor gating. PPI deficits are observed in humans and rats upon acute treatment with dopamine D2-like receptor agonists and in patients with schizophrenia. Repeated treatment with a D2-like agonist, however, reverses PPI deficits and increases cyclic adenosine monophosphate (cAMP) signaling in the nucleus accumbens (NAc). This study examined the short- and long-term effects on PPI of treatment with quinpirole and ropinirole, dopamine D2/D3 receptor agonists, and the molecular mechanism by which they occur. METHODS: PPI was assessed in adult male Sprague Dawley rats following acute and chronic treatment with quinpirole or ropinirole and 1, 2, 3, and 4 weeks after termination of repeated ropinirole treatment. Finally, the effect of dominant negative mutant cAMP response element binding protein (CREB) overexpression in the NAc on PPI following chronic quinpirole treatment was assessed. RESULTS: Acute quinpirole produced dose-dependent PPI deficits, whereas ropinirole caused consistent PPI reduction at all but the highest dose. Repeated ropinirole treatment significantly increased PPI compared with acute treatment, and increased CREB phosphorylation in NAc neurons. Subsequent ropinirole challenge had no effect as long as 28 days later, at which time NAc CREB phosphorylation had normalized. Overexpression of dominant negative mutant CREB prevented PPI recovery induced by chronic quinpirole treatment. CONCLUSIONS: Chronic quinpirole or ropinirole treatment produces sustained PPI recovery; CREB activity in the NAc is required to induce PPI recovery but not to maintain it. The results suggest that transcriptional regulation by CREB mediates long-lasting changes occurring within NAc circuits to promote recovery of sensorimotor gating. PMID- 21035787 TI - Fear extinction in traumatized civilians with posttraumatic stress disorder: relation to symptom severity. AB - BACKGROUND: The symptoms of posttraumatic stress disorder (PTSD) can be explained, at least in part, as an inability to inhibit learned fear during conditions of safety. Our group has shown that fear inhibition is impaired in both combat and civilian PTSD populations. On the basis of our earlier findings, we employed an established fear extinction paradigm to further explore fear dysregulation in a civilian traumatized population. METHODS: Fear-potentiated startle (FPS) was examined in 127 trauma-exposed individuals with and without PTSD. We used a protocol in which conditioned fear was first acquired through the presentation of one colored shape (reinforced conditioned stimulus, [CS+]) that was paired with an aversive air blast to the larynx (unconditioned stimulus) and a different colored shape that was not paired to the air blast (nonreinforced condition stimulus). Fear was extinguished 10 min later through repeated presentations of the CSs without reinforcement. RESULTS: Both groups demonstrated successful fear conditioning on the basis of startle and unconditioned stimulus expectancy ratings; however, participants with PTSD displayed greater FPS responses to the CS+ and nonreinforced conditioned stimulus compared with the group without PTSD. During fear extinction, the PTSD group showed elevated FPS responses to the previously reinforced CS+ during the early and middle stages of extinction. During the acquisition and extinction phases, PTSD participants with higher levels of reexperiencing symptoms exhibited greater potentiated startle responses to the CS+ compared with PTSD participants with lower reexperiencing symptoms. CONCLUSIONS: These results suggest that PTSD is associated with enhanced fear learning and a greater "fear load" to extinguish after conditioned fear is acquired. PMID- 21035788 TI - Reduced dorsal prefrontal gray matter after chronic ketamine use. AB - BACKGROUND: Use of ketamine as a recreational drug is spreading rapidly among young people all over the world. Epidemiological studies have linked chronic ketamine use with a number of problems, including cognitive impairments, bladder dysfunction, and ketamine-related death. However, little is known about the long term effects of ketamine use on brain structure and function. METHODS: We used voxel based morphometry in conjunction with statistical parametric mapping on the structural magnetic resonance images of ketamine-dependent (n = 41) and drug naive control individuals (n = 44) to assess differences in gray matter volume between the two groups. RESULTS: We observed significant decreases in gray matter volume in bilateral frontal cortex (left superior frontal gyrus and right middle frontal gyrus) of ketamine users in comparison with control subjects (p < .05 corrected for multiple comparisons at cluster-level). Duration of ketamine use was negatively correlated with gray matter volume in bilateral frontal cortex, whereas the estimated total lifetime ketamine consumption was negatively correlated with gray matter volume in left superior frontal gyrus. CONCLUSIONS: We have demonstrated a reduction in frontal gray matter volume in patients after chronic ketamine use. The link between frontal gray matter attenuation and the duration of ketamine use and cumulative doses of ketamine perhaps suggests a dose dependent effect of long-term use of the drug. Our results have important connotations for the clinical picture that is likely to emerge with the growing recreational use of ketamine and is also relevant to the status of the drug as a model for schizophrenia. PMID- 21035790 TI - Leptin regulates energy balance and motivation through action at distinct neural circuits. AB - BACKGROUND: Overconsumption of calorically dense foods contributes substantially to the current obesity epidemic. The adiposity hormone leptin has been identified as a potential modulator of reward-induced feeding. The current study asked whether leptin signaling within the lateral hypothalamus (LH) and midbrain is involved in effort-based responding for food rewards and/or the modulation of mesolimbic dopamine. METHODS: The contribution of endogenous leptin signaling for food motivation and mesolimbic dopamine tone was examined after viral-mediated reduction of the leptin receptor within LH and midbrain neurons in male rats. RESULTS: Knockdown of leptin receptors selectively in the LH caused increased body weight, caloric consumption, and body fat in rats maintained on a calorically dense diet. Knockdown of leptin receptors selectively in midbrain augmented progressive ratio responding for sucrose and restored high-fat, diet induced suppression of dopamine content in the nucleus accumbens. CONCLUSIONS: In summary, endogenous leptin signaling in the hypothalamus restrains the overconsumption of calorically dense foods and the consequent increase in body mass, whereas leptin action in the midbrain regulates effort-based responding for food rewards and mesolimbic dopamine tone. These data highlight the ability of leptin to regulate overconsumption of palatable foods and food motivation through pathways that mediate energy homeostasis and reward, respectively. PMID- 21035789 TI - Searching for neuropathology: gliosis in schizophrenia. AB - The neuropathology of schizophrenia remains elusive. One indication of this elusiveness is that the literature, in contrast to that on the neuropathology of almost any other disease, deals predominantly with measures of normal structures rather than with the demonstration and characterization of pathological structures. An important exception to this trend has been the continued search, over four decades, for reactive glia. In this article, we review histological and radiological evidence for and against astrocytosis and microgliosis specifically associated with schizophrenia. The studies are generally limited by small samples, flawed designs, and potentially biased methods of counting cells. Interpretation of these studies is further complicated by the frequent presence of glial reactions in older individuals without psychiatric disease. Nonetheless, some of the positive findings in the literature cannot easily be dismissed. A sufficiently large autopsy study, weighted toward younger subjects, could provide a definitive answer, which if positive could be a major step toward finding an underlying pathological process. PMID- 21035791 TI - The parent-of-origin of the extra X chromosome may differentially affect psychopathology in Klinefelter syndrome. AB - BACKGROUND: Several genetic mechanisms have been proposed for the variability of the Klinefelter syndrome (KS) phenotype such as the parent-of-origin of the extra X chromosome. Parent-of-origin effects on behavior in KS can possibly provide insights into X-linked imprinting effects on psychopathology that may be extrapolated to other populations. Here, we investigated whether the parent-of origin of the supernumerary X chromosome influences autistic and schizotypal symptom profiles in KS. METHODS: Parent-of-origin of the X chromosome was determined through analysis of the polymorphic CAG tandem repeat of the androgen receptor gene. Autistic traits (Autism Diagnostic Interview-Revised) were measured in a younger KS sample (n = 33) with KS and schizotypal traits (Schizotypal Personality Questionnaire) were assessed in an older KS sample (n = 43). Scale scores on these questionnaires were entered in statistical analyses to test parent-of-origin effects. RESULTS: The results show that parent-of-origin of the X chromosome is reflected in autistic and schizotypal symptomatology. Differences were shown in the degree of both schizotypal and autistic symptoms between the parent-of-origin groups. Furthermore, the parent-of-origin could be correctly discriminated in more than 90% of subjects through Autism Diagnostic Interview-Revised scales and in around 80% of subjects through Schizotypal Personality Questionnaire scales. CONCLUSIONS: These findings point to parent-of origin effects on psychopathology in KS and indicate that imprinted X chromosomal genes may have differential effects on autistic and schizotypal traits. Further exploration of imprinting effects on psychopathology in KS is needed to confirm and expand on our findings. PMID- 21035792 TI - Reduced dysbindin expression mediates N-methyl-D-aspartate receptor hypofunction and impaired working memory performance. AB - BACKGROUND: Schizophrenia is a heritable disorder associated with disrupted neural transmission and dysfunction of brain systems involved in higher cognition. The gene encoding dystrobrevin-binding-protein-1 (dysbindin) is a putative candidate gene associated with cognitive impairments, including memory deficits, in both schizophrenia patients and unaffected individuals. The underlying mechanism is thought to be based in changes in glutamatergic and dopaminergic function within the corticostriatal networks known to be critical for schizophrenia. This hypothesis derives support from studies of mice with a null mutation in the dysbindin gene that exhibit memory dysfunction and excitatory neurotransmission abnormalities in prefrontal and hippocampal networks. At a cellular level, dysbindin is thought to mediate presynaptic glutamatergic transmission. METHODS: We investigated the relationship between glutamate receptor dynamics and memory performance in dysbindin mutant mice. We assessed N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methylisoxazole 4-propionic acid receptor function in prefrontal cortex pyramidal neurons in vitro with whole-cell recordings, molecular quantitative analyses (reverse transcription-polymerase chain reaction) of the mandatory NMDA receptor subunit NR1, and cognitive function with a spatial working memory task. RESULTS: Decreases in dysbindin are associated with specific decreases in NMDA-evoked currents in prefrontal pyramidal neurons, as well as decreases in NR1 expression. Furthermore, the degree of NR1 expression correlates with spatial working memory performance, providing a mechanistic explanation for cognitive changes previously associated with dysbindin expression. CONCLUSIONS: These data show a significant downregulation of NMDA receptors due to dysbindin deficiency and illuminate molecular mechanisms mediating the association between dysbindin insufficiency and cognitive impairments associated with schizophrenia, encouraging study of the dysbindin/NR1 expression association in humans with schizophrenia. PMID- 21035794 TI - Chemical analysis of new water-soluble (1->6)-, (1->4)-alpha, beta-glucan and water-insoluble (1->3)-, (1->4)-beta-glucan (Calocyban) from alkaline extract of an edible mushroom, Calocybe indica (Dudh Chattu). AB - Two different glucans (PS-I, water-soluble; and PS-II, water-insoluble) were isolated from the alkaline extract of fruit bodies of an edible mushroom Calocybe indica. On the basis of acid hydrolysis, methylation analysis, periodate oxidation, and NMR analysis ((1)H, (13)C, DEPT-135, TOCSY, DQF-COSY, NOESY, ROESY, HMQC, and HMBC), the structure of the repeating unit of these polysaccharides were established as: PS-I: ->6)-beta-D-Glcp-(1->6)-beta-D-glcp-(1 >6)-)-beta-D-Glcp-(1-> alpha-D=Glcp (Water-soluble glucan). PS-II: ->3)-beta-D Glcp-(1->3)-beta-D-glcp-(1->3)-)-beta-D-Glcp-(1->3)-beta-D-Glcp-(1-> beta-D-Glcp (Water-insoluble glucan, Calocyban). PMID- 21035793 TI - Disrupted axonal fiber connectivity in schizophrenia. AB - BACKGROUND: Schizophrenia is believed to result from abnormal functional integration of neural processes thought to arise from aberrant brain connectivity. However, evidence for anatomical dysconnectivity has been equivocal, and few studies have examined axonal fiber connectivity in schizophrenia at the level of whole-brain networks. METHODS: Cortico-cortical anatomical connectivity at the scale of axonal fiber bundles was modeled as a network. Eighty-two network nodes demarcated functionally specific cortical regions. Sixty-four direction diffusion tensor-imaging coupled with whole-brain tractography was performed to map the architecture via which network nodes were interconnected in each of 74 patients with schizophrenia and 32 age- and gender matched control subjects. Testing was performed to identify pairs of nodes between which connectivity was impaired in the patient group. The connectional architecture of patients was tested for changes in five network attributes: nodal degree, small-worldness, efficiency, path length, and clustering. RESULTS: Impaired connectivity in the patient group was found to involve a distributed network of nodes comprising medial frontal, parietal/occipital, and the left temporal lobe. Although small-world attributes were conserved in schizophrenia, the cortex was interconnected more sparsely and up to 20% less efficiently in patients. Intellectual performance was found to be associated with brain efficiency in control subjects but not in patients. CONCLUSIONS: This study presents evidence of widespread dysconnectivity in white-matter connectional architecture in a large sample of patients with schizophrenia. When considered from the perspective of recent evidence for impaired synaptic plasticity, this study points to a multifaceted pathophysiology in schizophrenia encompassing axonal as well as putative synaptic mechanisms. PMID- 21035795 TI - Perception of intersensory synchrony in audiovisual speech: not that special. AB - Perception of intersensory temporal order is particularly difficult for (continuous) audiovisual speech, as perceivers may find it difficult to notice substantial timing differences between speech sounds and lip movements. Here we tested whether this occurs because audiovisual speech is strongly paired ("unity assumption"). Participants made temporal order judgments (TOJ) and simultaneity judgments (SJ) about sine-wave speech (SWS) replicas of pseudowords and the corresponding video of the face. Listeners in speech and non-speech mode were equally sensitive judging audiovisual temporal order. Yet, using the McGurk effect, we could demonstrate that the sound was more likely integrated with lipread speech if heard as speech than non-speech. Judging temporal order in audiovisual speech is thus unaffected by whether the auditory and visual streams are paired. Conceivably, previously found differences between speech and non speech stimuli are not due to the putative "special" nature of speech, but rather reflect low-level stimulus differences. PMID- 21035796 TI - Valuation of environmental quality and eco-cultural attributes in Northwestern Idaho: Native Americans are more concerned than Caucasians. AB - Valuation of features of habitats and ecosystems usually encompasses the goods and services that ecosystems provide, but rarely also examine how people value ecological resources in terms of eco-cultural and sacred activities. The social, sacred, and cultural aspects of ecosystems are particularly important to Native Americans, but western science has rarely examined the importance of eco-cultural attributes quantitatively. In this paper I explore differences in ecosystem evaluations, and compare the perceptions and evaluations of places people go for consumptive and non-consumptive resource use with evaluations of the same qualities for religious and sacred places. Qualities of ecosystems included goods (abundant fish and crabs, butterflies and flowers, clean water), services (complexity of nature, lack of radionuclides that present a health risk), and eco cultural attributes (appears unspoiled, scenic horizons, noise-free). Native Americans and Caucasians were interviewed at a Pow Wow at Post Falls, Idaho, which is in the region with the Department of Energy's Hanford Site, known for its storage of radioactive wastes and contamination. A higher percentage of Native American subjects engaged in consumptive and religious activities than did Caucasians. Native Americans engaged in higher rates of many activities than did Caucasians, including commune with nature, pray or meditate, fish or hunt, collect herbs, and conduct vision quests or other ceremonies. For nearly all attributes, there was no difference in the relative ratings given by Native Americans for characteristics of sites used for consumption/non-consumptive activities compared to religious/sacred places. However, Caucasians rated nearly all attributes lower for religious/sacred places than they did for places where they engaged in consumptive or non-consumptive activities. Native Americans were less concerned with distance from home for consumptive/non-consumptive activities, compared to religious activities. PMID- 21035797 TI - Specific accumulation of CYP94A1 transcripts after exposure to gaseous benzaldehyde: induction of lauric acid omega-hydroxylase activity in Vicia sativa exposed to atmospheric pollutants. AB - The effects of air pollutants such as aldehydes, ozone, nitrogen dioxide and benzene on fatty acid omega-hydroxylase activity in Vicia sativa microsomes have been investigated. Four days old etiolated V. sativa seedlings were exposed to different concentrations of selected pollutants for varying exposure times. Growing etiolated V. sativa seedlings in air containing the gaseous benzaldehyde (150 nM) led to an 8-fold enhancement of lauric acid omega-hydroxylase activity in microsomes of treated plants compared to controls grown in pure air (96 +/- 10 versus 12 +/- 2 pmol/min/mg protein, respectively). The induction increased with increasing gas phase concentrations (10-1300 nM) and the maximum of activity was measured after 48 h of exposure. Northern blot analysis revealed that this induction occurred via transcriptional activation of the gene coding for CYP94A1. The absence of CYP94A2 and CYP94A3 transcription activation together with the missing effect on epoxide hydrolases activities indicate the specificity of CYP94A1 induction by benzaldehyde. Exposure to nitrogen dioxide, ozone and formaldehyde also stimulated lauric acid omega-hydroxylases activity while exposure to benzene did not show any effect. PMID- 21035798 TI - Cytomegalovirus-induced small-bowel bleeding detected by capsule endoscopy. PMID- 21035799 TI - Double-balloon enteroscopy for multiple ischemic stenoses in the jejunum caused by cholesterol crystal embolisms. PMID- 21035800 TI - Inner-city gunshot wounds-10 years on. AB - INTRODUCTION: In 1997, Injury published one of the first research papers to document the incidence and characteristics of civilian gunshot wounds in a UK urban environment. Since then there has been concern that firearm deaths and injuries have increased despite little published clinical evidence. METHODS: We carried out a retrospective survey ten years on from the initial study. All patients presenting to the Emergency Department (ED) of King's College Hospital with gunshot wounds from 1st January 2003 to 31st December 2004 were identified. Information regarding incidence, patient and injury characteristics and outcome was determined. RESULTS: 46 patients presented with firearm injuries. 44 were male and the average age was 24 years. The majority were from minority ethnic groups. 38/46 presented out of hours and the police were documented to be involved in 36 cases. All injuries were due to assault by low energy projectiles. Of the 32 patients admitted the mean length of stay was 12.4 days. The majority of injuries were to the musculo-skeletal system. Six patients died from their injuries-5 from head/neck or chest injuries and 1 from intra-abdominal injury. DISCUSSION: There appears to be little increase in firearm injuries seen over this 10 year period at our hospital and predominately young, black males continue to be the victims. Most present out of hours,potentially placing considerable challenges on junior medical staff. Most wounds were to the musculoskeletal system perhaps reflecting the desire to maim rather than kill and the absence of high velocity injuries may reflect the UK's stringent gun control legislation. The importance of high quality clinical audit is necessary to effectively plan training, service provision and violence prevention efforts. CONCLUSION: Despite public, political and media concerns that deaths and injuries caused by firearm shave increased dramatically, this study finds little change in incidence or characteristics of those injured and attending an urban ED over a ten year period. PMID- 21035801 TI - Is revision surgery following lower-limb amputation a worthwhile procedure? A retrospective review of 71 cases. AB - There is little written about the value of revision surgery on lower-limb amputations. We report on 71 revision amputation procedures performed by a single surgeon in this retrospective analysis. The majority of our revisions (61%) were in amputees who had suffered trauma. We judged success from a surgical and a rehabilitation perspective using scoring systems. Revisions for bony and soft tissue pathology had good outcomes from a surgical (85% and 82%) and a rehabilitation perspective. Revisions for infection had satisfactory results from a surgical perspective (73%) but less so from a rehabilitation perspective (25%). The results of the revisions for pain were poor showing surgical success only 50% of the time where a neuroma was suspected and only 25% when there was no apparent cause. There was little or no improvement in rehabilitation in both the pain groups. Revision surgery for certain pathologies gives a good surgical outcome and can improve pain and mobility status. Patient selection for surgery is key and evaluation by a multidisciplinary team is recommended. PMID- 21035802 TI - Pro-inflammatory activities induced by CyPA-EMMPRIN interaction in monocytes. AB - Excessive reactive oxygen species (ROS) is a critical driver of vascular inflammation in atherosclerosis. Cyclophilin A (CyPA) is the main ROS-induced factor that enhances the inflammatory activity of monocytes/macrophages in atherosclerotic plaque. However, the means by which CyPA interacts with monocytes/macrophages is unclear. Through Chemotaxis assay and ELISA test, we found CyPA strongly induced migration of monocytes and the expression of mmp-9, IL-6 and TNF-alpha. By Western blot, it demonstrated that CyPA activated NF kappaB by ERK1/2 pathway. When blocking extracellular matrix metalloproteinase inducer (EMMPRIN) in monocytes, most of the CyPA effects including chemoattractant migration, activation of MAPK/NF-kappaB and cytokines releasing were significantly inhibited. Finally, CyPA simulation had no effect on EMMPRIN expression in monocytes. The current study shows that CyPA-EMMPRIN interaction is one of the key pro-inflammatory signaling pathways in monocytes, perhaps especially in response to ROS stimulation. This could be a potential target for atherosclerosis therapy. PMID- 21035805 TI - Comparative qualitative analysis of nonylphenol isomers by gas chromatography mass spectrometry combined with chemometric resolution. AB - The relationship between nonylphenol (NP) isomers' structures and their estrogenic potencies has been evaluated previously. However, due to their similarities in both chemical and physical properties, complete separation and identification remain strikingly difficult. In the present study, gas chromatography-mass spectrometry (GC-MS) is employed to separate commercial NP isomers. Both extracted ion chromatograms (EIC) based on selected ions known to be definitive for the suite of isomers, and the heuristic evolving latent projection (HELP) chemometric resolution method have been applied for the analysis and identification of the NP isomers. This method corrected the wrong identification of one isomer which was suspected based on the EIC data, and also was able to be applied for the determination of an additional isomer with low abundance. Overall, 15 NP isomers have been proposed by the HELP interpretation method. Pure component chromatograms and mass spectra have been extracted with the aid of chemometric resolution. The applicability of the commercial deconvolution software package automated mass spectral deconvolution and identification system (AMDIS) has also been tested against the HELP method for comparative presentation of pure component mass spectra. PMID- 21035803 TI - Abdominal aortic calcium and multi-site atherosclerosis: the Multiethnic Study of Atherosclerosis. AB - BACKGROUND: Abdominal aortic calcification (AAC) is a measure of subclinical cardiovascular disease (CVD). Data are limited regarding its relation to other measures of atherosclerosis. METHODS: Among 1812 subjects (49% female, 21% black, 14% Chinese, and 25% Hispanic) within the population-based Multiethnic Study of Atherosclerosis, we examined the cross-sectional relation of AAC with coronary artery calcium (CAC), ankle brachial index (ABI), and carotid intimal medial thickness (CIMT), as well as multiple measures of subclinical CVD. RESULTS: AAC prevalence ranged from 34% in those aged 45-54 to 94% in those aged 75-84 (p < 0.0001), was highest in Caucasians (79%) and lowest in blacks (62%) (p < 0.0001). CAC prevalence, mean maximum CIMT >= 1mm, and ABI < 0.9 was greater in those with vs. without AAC: CAC 60% vs. 16%, CIMT 38% vs. 7%, and ABI 5% vs. 1% for women and CAC 80% vs. 37%, CIMT 43% vs. 16%, and ABI 4% vs. 2% for men (p < 0.01 for all except p < 0.05 for ABI in men). The substantially greater prevalence for CAC in men compared to women all ages is not seen for AAC. By age 65, 97% of men and 91% of women have AAC, CAC, increased CIMT, and/or low ABI. The presence of multi site atherosclerosis (>= 3 of the above) ranged from 20% in women to 30% in men (p < 0.001), was highest in Caucasians (28%) and lowest in Chinese (16%) and ranged from 5% in those aged 45-54 to 53% in those aged 75-84 (p < 0.01 to p < 0.001). Finally, increased AAC was associated with 2-3-old relative risks for the presence of increased CIMT, low ABI, or CAC. CONCLUSIONS: AAC is associated with an increased likelihood of other vascular atherosclerosis. Its additive prognostic value to these other measures is of further interest. PMID- 21035807 TI - Analysis and study of the distribution of polar and non-polar pesticides in wastewater effluents from modern and conventional treatments. AB - The analysis of a wide range of pesticides in wastewaters (WWs) undergoing different treatments (both modern and conventional) has been studied. The need for optimizing specific extraction methods for each WW effluent based on their physico-chemical characteristics has been considered. A distribution study was performed to establish if the filtration step before extraction is a correct procedure since pesticides can be more prone to be in the aqueous or the solid phase, depending on their hydrophobicity. This evaluation demonstrated that pesticides are distributed between the aqueous phase and the suspended particulate matter (SPM; e.g. pyrethroids are only found in the SPM). The proposed methodologies involved the determination of 39 polar and 139 non-polar pesticides using solid-phase extraction (SPE) and pressurized-liquid extraction (PLE) for the extraction of the aqueous phase and the SPM, respectively. Ultra high pressure liquid chromatography and gas chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS, GC-MS/MS) were used in the determination stage. WW samples from four different technologies were evaluated: membrane bioreactor, extended aeration, maturation pond and anaerobic pond. Validation data for the four effluents studied were generated, obtaining adequate precision values (estimated as % relative standard deviation, RSD) in almost all cases (<25%). The methods showed limits of detection at 0.01-0.20MUgL(-1) and limits of quantification from 0.02 to 0.50MUgL(-1). The proposed methods were applied to the analysis of real samples collected from an experimental WW treatment plant, detecting non-polar and polar pesticides at concentrations in the range 0.02 1.94MUgL(-1) and 0.02-0.33MUgL(-1), respectively. PMID- 21035804 TI - Measurement of Rho-associated kinase (ROCK) activity in humans: validity of leukocyte p-MBS/t-MBS in comparison with vascular response to fasudil. AB - BACKGROUND: Rho-associated kinases (ROCKs) have been shown to be involved in the pathogenesis of atherosclerosis. It is clinically important to estimate the degree of ROCK activity in humans. The purpose of this study was to confirm the validity of a leukocyte ROCK parameter as an index of ROCK activity in comparison with vascular response to a ROCK inhibitor. METHODS AND RESULTS: We evaluated the ratio of phospho myosin-binding subunit (p-MBS) on myosin light-chain phosphatase to total MBS in peripheral leukocytes by Western blot analysis and forearm blood flow (FBF) response to the ROCK inhibitor fasudil using strain-gauge plethysmography in 36 healthy subjects and 39 patients with cardiovascular diseases. Fasudil (3, 10, 30MUg/min) was infused intra-arterially for 5min at each dose. Leukocyte p-MBS/total-MBS was higher in cardiovascular diseases than in healthy subjects (0.97+/-0.37 vs. 0.51+/-0.14; P=0.002). Fasudil increased FBF from 4.9+/-1.2 to 14.5+/-5.7mL/min/100mL tissue (P<0.0001) in patients with cardiovascular diseases, while fasudil did not alter FBF in healthy subjects. There was a significant relationship between leukocyte p-MBS/total-MBS and maximal FBF response to fasudil in all subjects (r=0.72, P<0.0001). There was also a significant correlation between p-MBS/total-MBS and maximal FBF response to fasudil in patients with cardiovascular diseases (r=0.59, P<0.0001). In healthy subjects, there was no significant correlation between the two parameters. CONCLUSIONS: These findings suggest that assessment of leukocyte ROCK activity is minimally invasive and does not require pharmacologic intervention using ROCK inhibitors. Leukocyte p-MBS/total-MBS may be useful for evaluating ROCK activity in a clinical setting. PMID- 21035808 TI - Comparative study of two extraction techniques to obtain representative aroma extracts for being analysed by gas chromatography-olfactometry: application to roasted pistachio aroma. AB - This research paper presents a comparative study of two different extraction and concentration techniques to obtain representative pistachio aroma extracts: the traditional direct solvent extraction (DSE) followed by high-vacuum transfer (HVT) and the headspace solid-phase microextraction (HS-SPME). The results showed that, although both techniques provide accurate information about the aromatic composition that will be perceived by the consumer, the precision in terms of within-day repeatability and between-days repeatability (intermediate precision) of the chromatographic areas presented better values for HS-SPME than for DSE HVT. Moreover the solvent-free HS-SPME allows the extraction of more odour-active regions, requires very little sample handling and shorter time for sampling. PMID- 21035809 TI - Elution behavior of polyethylene and polypropylene standards on carbon sorbents. AB - The elution behavior of linear polyethylene and isotactic, atactic and syndiotactic polypropylene was tested using three different carbon column packings: porous graphite (Hypercarb), porous zirconium oxide covered with carbon (ZirChrom-CARB), and activated carbon TA 95. Several polar solvents with boiling points above 150 degrees C were selected as mobile phases: 2-ethyl-1-hexanol, n decanol, cyclohexylacetate, hexylacetate, cyclohexanone, ethylene glycol monobutyl ether and one non-polar solvent, n-decane. Polyethylene standards were completely or partially adsorbed in all tested sorbent/solvent systems. Polypropylene standards were partially adsorbed on Hypercarb and carbon TA95, but did not adsorb on ZirChrom-CARB. ZirChrom-CARB retained polyethylene pronouncedly when 2-ethyl-1-hexanol, cyclohexylacetate or hexylacetate were used as mobile phases at temperature 150 or 160 degrees C, while all three basic stereoisomers of polypropylene eluted in size exclusion mode in these sorbent/solvent pairs. This is very different from the system Hypercarb/1-decanol, which separated polypropylene according to its tacticity. The opposite elution behavior of polyethylene and polypropylene in system ZirChrom-CARB/2-ethyl-1-hexanol (polypropylene eluted, polyethylene fully adsorbed) enabled to realize separation of blends of polyethylene and polypropylene. Ethylene/1-hexene copolymers were separated according to their chemical composition using system Hypercarb/2-ethyl 1-hexanol/1,2,4-trichlorobenzene. PMID- 21035810 TI - Development of a solid-phase extraction with capillary liquid chromatography tandem mass spectrometry for analysis of estrogens in environmental water samples. AB - Capillary liquid chromatography (cLC) hyphenated with tandem mass spectrometry (MS-MS) was used to separate and quantitate trace concentrations of five estrogens in aqueous samples. New C(18)-based sorption materials bound to the silica support by monomeric and polymeric mechanisms were compared and tested for solid-phase extraction (SPE) of selected analytes with respect to optimization of their preconcentration yield. Application of an endcapped, monomer-bound preconcentration Discovery DSC-18Lt column under the optimized conditions provides yields in the range from 95 to 100% with a high repeatability (n=3, RSD<=7.2%). Using the electrospray ionization in the positive mode (ESI+), the cLC-MS-MS system (the Zorbax SB C18 capillary column and a binary mobile phase of acetonitrile and water containing 0.1% formic acid in both the components) was optimized to attain a sufficient retention of the early eluting estriol, a satisfactory resolution of the analytes and the maximum sensitivity of the determination. Both the isocratic and gradient elution were used and the optimized gradient method permitted analyses of aqueous environmental samples in 14 min within a linearity range from 6.1 to 25.0 (LOQ of analytes) to 500 ng/L and with a very good linearity (r>0.9981) for all the estrogens studied. The detection limits are in the range from 3.0 to 6.8 ng/L (1 MUL injection volume). Six environmental water samples were analyzed and the studied estrogens were found in the Vltava river sample collected in Prague (13.2 ng/L for 17beta estradiol) and in the inlet to the wastewater treatment plant in Prague, at an overall concentration of 371.4 ng/L. PMID- 21035811 TI - Reversed-phase high-performance liquid chromatographic separation of diastereomers of (R,S)-mexiletine prepared by microwave irradiation with four new chiral derivatizing reagents based on trichloro-s-triazine having amino acids as chiral auxiliaries and 10 others having amino acid amides. AB - A new series of chiral derivatizing reagents (CDRs) consisting of four dichloro-s triazine reagents was synthesized by nucleophilic substitution of one chlorine atom in trichloro-s-triazine with amino acids, namely L-Leu, D-Phg, L-Val and L Ala as chiral auxiliaries. Two other sets of CDRs consisting of four dichloro-s triazine (DCT) and six monochloro-s-triazine (MCT) reagents were also prepared by nucleophilic substitution of chlorine atom(s) with different amino acid amides as chiral auxiliaries in trichloro-s-triazine and its 6-methoxy derivative, respectively. These 14 CDRs were used for the synthesis of diastereomers of (R,S) mexiletine under microwave irradiation (i.e. 60s and 90 s at 85% power (of 800 W) using DCT and MCT reagents, respectively), which were resolved by reversed-phase high-performance liquid chromatography using C18 column and gradient eluting mixtures of methanol with aqueous trifluoroacetic acid (TFA) with UV detection at 230 nm. The resolution (R(s)), difference between retention times of resolved diastereomers (Deltat) and retention factors (k) obtained for the three sets of diastereomers were compared among themselves and among the three groups. Explanations have been offered for longer retention times and better resolution of diastereomers prepared with DCT reagents in comparison of their MCT counterparts and, for the influence of hydrophobicity of the side chain R of the amino acid in the CDRs on retention times and resolution. The newly synthesized CDRs were observed to be superior as compared to their amide counterparts in terms of providing better resolution and cost effectiveness. The method was validated for limit of detection, linearity, accuracy and precision. PMID- 21035812 TI - Optimisation of a dispersive liquid-liquid microextraction method for the simultaneous determination of halophenols and haloanisoles in wines. AB - A dispersive liquid-liquid microextraction (DLLME) method has been optimised for simultaneously extracting 2,4,6-trichloranisole (TCA), 2,3,4,6-tetrachloroanisole (TeCA), 2,4,6-tribromoanisole (TBA), pentachloroanisole (PCA), 2,4,6 trichlorophenol (TCP), 2,3,4,6-tetrachlorophenol (TeCP), 2,4,6-tribromophenol (TBP) and pentachlorophenol (PCP) from wine. The haloanisoles and halophenols were automatically determined using a gas chromatography-electron-capture detection (GC-ECD) system. Derivatisation of halophenols was performed at the same time as DLLME. Firstly, disperser and extraction solvents, salt addition and temperature conditions were selected. Then, the volume of disperser solvent, extraction solvent and derivatisation agent, and the percentage of base were optimised by means of a central composite design combined with desirability functions. The optimal extraction-derivatisation conditions found were 1.3 mL of acetone, 150 MUL of carbon tetrachloride, 75 MUL of acetic anhydride and a percentage of base of 0.7%; with no salt addition and at room temperature. Under these conditions, the proposed method showed satisfactory linearity (with correlation coefficients over 0.994), repeatability (below 9.7%) and reproducibility (below 9.9%). Moreover, detection limits were lower than the olfactory threshold of the compounds. The developed method was successfully applied to the analysis of red wine samples. To our knowledge, this is the first time that DLLME has been applied to determine cork taint responsible compounds in wine. PMID- 21035813 TI - One-step aqueous synthesis of graphene-CdTe quantum dot-composed nanosheet and its enhanced photoresponses. AB - Although CdTe nanocrystal has been applied in quantum dot (QD)-based solar cells, there is no report on a graphene-CdTe QD hybrid system and its photoresponses. In this work, graphene-CdTe QD composed nanosheets were one-step synthesized in aqueous solution using a hydrothermal method and demonstrated enhanced photoresponses, rendering potentials in optoelectronics applications. This work could provide an environmental-friendly and universal approach to fabricate graphene-based hybrid nanomaterials for various applications. PMID- 21035814 TI - Photodegradation activity of polyvinyl chloride (PVC)-perchlorinated iron (II) phthalocyanine (FePcCl16) composite film. AB - In this paper, a novel kind of photodegradable PVC-FePcCl(16) composite film was prepared by homogeneous embedding FePcCl(16) into the commercial PVC plastic. The photodegradation performance of as-prepared film has been investigated in the ambient air under UV light irradiation by means of weight loss monitoring, FT-IR spectroscopy, UV-Vis spectroscopy. In comparison with the pure PVC film, higher weight loss rate, increasing carbonyl peak intensity and accelerating dehydrochlorination were observed. These results indicate that the PVC-FePcCl(16) composite film has a higher photodegradation activity owing to the FePcCl(16). Moreover, FePcCl(16) has good photostability in the photoreaction. The possible photodegradation mechanism of PVC-FePcCl(16) composite film was also discussed. PMID- 21035815 TI - Synthesis and characterization of nanomagnetite particles and their polymer coated forms. AB - Superparamagnetic nanoparticles were prepared by coprecipitation of ferrous (Fe(2+)) and ferric (Fe(3+)) aqueous solution by a base. Nanomagnetite particles were coated with poly(St/PEG-EEM/DMAPM) and poly(St/PEG-MA/DMAPM) layer by emulsifier-free emulsion polymerization. Chemical structure of nanoparticles was characterized by both FTIR and (1)H NMR. Particle morphologies were determined by Zeta Sizer, DLS, XRD and SAXS. Structural analysis showed that after polymer coating nanomagnetite particles kept their superparamagnetic property. Besides the synthesized magnetites, polymer coated forms of these particles are more biocompatible, well dispersable and uniform. These properties make them a very strong candidate for bioengineering applications, such as bioseparation, gene transfer. PMID- 21035816 TI - Inverse opal photonic crystal of chalcogenide glass by solution processing. AB - Chalcogenide opal and inverse opal photonic crystals were successfully fabricated by low-cost and low-temperature solution-based process, which is well developed in polymer films processing. Highly ordered silica colloidal crystal films were successfully infilled with nano-colloidal solution of the high refractive index As(30)S(70) chalcogenide glass by using spin-coating method. The silica/As-S opal film was etched in HF acid to dissolve the silica opal template and fabricate the inverse opal As-S photonic crystal. Both, the infilled silica/As-S opal film (Deltan ~ 0.84 near lambda=770 nm) and the inverse opal As-S photonic structure (Deltan ~ 1.26 near lambda=660 nm) had significantly enhanced reflectivity values and wider photonic bandgaps in comparison with the silica opal film template (Deltan ~ 0.434 near lambda=600 nm). The key aspects of opal film preparation by spin-coating of nano-colloidal chalcogenide glass solution are discussed. The solution fabricated "inorganic polymer" opal and the inverse opal structures exceed photonic properties of silica or any organic polymer opal film. The fabricated photonic structures are proposed for designing novel flexible colloidal crystal laser devices, photonic waveguides and chemical sensors. PMID- 21035817 TI - Population-based health requires population-based change. PMID- 21035818 TI - Does timing matter? A national perspective on the risk of incarceration in premature neonates with inguinal hernia. AB - OBJECTIVES: To determine the incidence of inguinal hernia in premature neonates and identify risk factors for incarceration. STUDY DESIGN: The 2003 and 2006 Kids' Inpatient Databases were queried for diagnoses indicative of premature birth and inguinal hernia. RESULTS: Inguinal hernia was diagnosed during the birth hospitalization in 1463 +/- 87 of 49 273 +/- 1561 premature neonates (3%). Male sex, gestational age, birth weight, and prolonged mechanical ventilation were associated with inguinal hernia (all P < .01). Incarceration occurred in 176 of 1123 premature neonates (16%) who underwent hernia repair during the birth hospitalization. Delaying repair beyond 40 weeks post-conceptual age doubled the risk of incarceration (21%), as compared with 36 to 39 weeks (9%) or <36 weeks (11%, P = .002). Sex, race, and insurance were not associated with incarceration. CONCLUSION: The risk of incarceration is doubled in premature neonates with inguinal hernia when repair is delayed beyond 40 weeks post-conceptual age. This increased incarceration risk should be one of the factors considered when deciding on the optimal timing of inguinal hernia repair. PMID- 21035819 TI - Are guidelines for glucocorticoid coverage in adrenal insufficiency currently followed? AB - OBJECTIVES: To search for evidence of acute adrenal failure linked to inappropriate use of stress management protocols. STUDY DESIGN: Patients followed up for primary adrenal insufficiency (n = 102) or secondary adrenal insufficiency (n = 34) between 1973 and 2007 were included. All hospitalizations, both urgent (n = 157) and elective (n = 90), were examined. We recorded clinical evidence of acute adrenal failure, parental management before admission, and details of glucocorticoid prescription and administration in the hospital setting. RESULTS: For urgent hospitalizations, subgroup and time period did not influence the percentage of patients hospitalized (primary adrenal insufficiency 45%; secondary adrenal insufficiency 38%; P = .55). The use of stress glucocorticoid doses by parents increased significantly after 1997 (P < .05), although still only 47% increased glucocorticoids before hospitalization. Stress doses were more frequently administered on arrival in our emergency department after 1990 (P < .05); patients with signs or symptoms of acute adrenal failure decreased to 27% after 1997 (P < .01). Twenty-four percent of all hospitalizations were marked by suboptimal adherence to glucocorticoid stress protocols, with rare but significant clinical consequences. CONCLUSIONS: In spite of an increased use of glucocorticoid stress dose protocols by parents and physicians, patients remain at risk of morbidity and death from acute adrenal failure. This risk may be minimized with conscientious application of stress protocols, but other patient specific risk factors may also be implicated. PMID- 21035820 TI - Hyperglycemic hyperosmolar syndrome in children: pathophysiological considerations and suggested guidelines for treatment. PMID- 21035821 TI - Add-on therapy with subcutaneous treprostinil for refractory pediatric pulmonary hypertension. AB - OBJECTIVE: To evaluate the efficacy and tolerability of subcutaneous (SC) treprostinil, a prostacyclin analogue, in young children with refractory pulmonary arterial hypertension. STUDY DESIGN: Eight children (median age, 4 years) received SC treprostinil therapy after failure of combined oral treatment (n = 7) or because of severe complications with intravenous epoprostenol (n = 1). Treprostinil was delivered through an SC catheter at gradually increasing doses to an average of 40 ng/kg/min, depending on the presence of adverse effects. RESULTS: Seven patients demonstrated early significant improvement (in functional class, hemodynamics, and/or 6-minute walk distance; P <.05), and 6 had a sustained good response. Site pain could be effectively managed in all but one child. CONCLUSIONS: Treprostinil may be a potentially valuable rescue therapy in children with refractory pulmonary arterial hypertension, but further study in a larger number of patients is needed. PMID- 21035822 TI - Smaller weight changes in standardized body mass index in response to treatment as weight classification increases. AB - OBJECTIVES: To compare the differential efficacy of a weight loss program for Mexican-American children who are overweight, obese, and severely obese. STUDY DESIGN: Study participants were enrolled in an intensive weight loss intervention aimed at improving eating and physical activity behaviors with behavior modification strategies. Participants included 212 children (45% female) between the ages of 9 and 14 (mean = 12.0, standard deviation = 0.7). All participants were classified as overweight, obese, or severely obese. RESULTS: Repeated measures analyses revealed that children in the overweight, obese, and severely obese weight categories differed significantly in standardized body mass index (zBMI) decreases at baseline, 3, 6, and 12 months (F = 4.57, P < .01, eta(p)(2) = .06). Follow-up paired samples t tests showed a significant change in zBMI from baseline to 3 and 6 months for children in the overweight, obese, and severely obese weight categories. However, at 12 months only the overweight and obese students continued to show significant improvement from baseline in zBMI. CONCLUSIONS: These findings suggest that an intensive behavioral weight loss intervention that has demonstrated efficacy for decreasing zBMI may have incrementally smaller effects for children as weight classification increases. PMID- 21035824 TI - [Thirty years of laser-assisted microvascular anastomosis (LAMA): what are the clinical perspectives?]. AB - INTRODUCTION: Since the first studies by Jain and Gorisch (1979), laser-assisted anastomoses have been steadily developed to a stage where clinical use is within reach. The laser-assisted vascular microanastomosis (LAMA) procedure is performed more quickly than conventional anastomosis, the surgically induced vessel damage is limited, and reduced bleeding after unclamping is observed. MATERIAL AND METHODS: A Medline literature search, for the January 1979 to February 2010 period, was performed to review articles focusing on the LAMA technique. RESULTS: The search yielded a total of 354 publications, of which 87 were relevant: 82 were animal series and five clinical studies. Microsurgical techniques and principal characteristics of LAMA in patients are the focus of the analysis. This study discusses the technological innovations and new orientations in laser welding. CONCLUSION: The first two clinical series using the 1.9-MUm diode laser appear promising. Technical innovation will most likely lead to greater ease of use of the laser handpiece in the operating room. PMID- 21035823 TI - Genetic variation of the ghrelin activator gene ghrelin O-acyltransferase (GOAT) is associated with anorexia nervosa. AB - The gastrointestinal peptide hormone ghrelin promotes food intake and increases body weight and adiposity through activation of the growth hormone secretagogue receptor (GHSR1a). To promote its biological action ghrelin is acylated at its serine 3 residue by the recently discovered ghrelin O-acyltransferase (GOAT, a.k.a. membrane-bound O-acyltransferase 4, MBOAT4). Plasma levels of total and acyl-ghrelin are negatively correlated with body-mass-index (BMI); as lower the BMI as higher plasma levels of total and acylated ghrelin and vice versa. Accordingly, plasma levels of total and acyl-ghrelin are elevated in patients with anorexia nervosa (AN) and decline upon weight regain. The importance of the endogenous Goat/ghrelin system in the neuroendocrine adaptation to fasting was recently highlighted by the observation that acyl-ghrelin mediated elevation of growth hormone (GH) release prevents starvation induced hypoglycemia in Goat(-/-) mice. The aim of this study was to test if genetic variation of GOAT is implicated in the etiology of AN. We therefore assessed association of 6 tagging single nucleotide polymorphisms (tagSNPs), which were predicted to cover 96% the common genetic variability of GOAT plus 50 kb of the 5' and 3' flanking region, in 543 German patients with AN and 612 German normal and underweight healthy controls. Based on a recessive mode of inheritance we observed some evidence for association of the G/G genotype at SNP rs10096097 with AN (nominal two-sided p = 0.031). Based on our results we conclude that genetic variation in GOAT might be implicated in the etiology of AN. PMID- 21035825 TI - Influence of sociodemographic inequalities and chronic conditions on influenza vaccination coverage in Italy: results from a survey in the general population. AB - OBJECTIVE: To assess inequalities in vaccination against seasonal influenza determined by sociodemographic and health-related factors. STUDY DESIGN: A cross sectional study was conducted using data from 128,040 subjects aged 1-89 years who participated the national survey 'Health Conditions and Health Care Services Use', conducted by the Italian National Centre of Statistics in 2005. METHODS: This analysis included people aged >=65 years, and individuals of any age with chronic medical conditions. The outcome variable was vaccination or non vaccination against influenza in the last 12 months, and the explanatory variables were gender, age, smoking habit, educational level, macro-region of residence, chronic medical conditions, occupational status, marital status, self assessed health status and self-assessed household income. Univariate and multivariate analyses were conducted using Chi-squared test and multiple logistic regression models. For the latter analysis, results are presented as odds ratios (OR) and 95% confidence intervals (CI) of being vaccination against influenza in the last 12 months. RESULTS: Approximately 20% of subjects had been vaccinated against influenza in the previous 12 months. Older age (>=65 years), current smoker, poor health status, poor self-assessed household income and the presence of at least one chronic condition were positively associated with influenza vaccination (P < 0.05). The lowest ORs for influenza vaccination were found in current smokers (adjusted OR vs non-smokers 0.699, 95% CI 0.697-0.701), young adults (adjusted OR 15-24 years vs >=65 years 0.073, 95% CI 0.072-0.073; adjusted OR 25-34 years vs >=65 years 0.097, 95% CI 0.096-0.097), subjects with a lower secondary education or professional school (adjusted OR vs primary education 0.910, 95% CI 0.908-0.913), subjects living in the Islands (adjusted OR vs North eastern Italy 0.760, 95% CI 0.757-0.763), and unemployed subjects (adjusted OR vs employed 0.867; 95% CI 0.859-0.875). The ORs for vaccination were lower for some chronic conditions (e.g. allergies, cirrhosis) than others (e.g. cancer, stroke, bronchitis). Younger age groups, including children aged 0-14 years, had lower ORs for vaccination. CONCLUSIONS: Socio-economic factors, such as gender, age, educational level, occupational status and macro-region of residence, affect influenza vaccination coverage rates in the Italian general population. In addition, some chronic medical conditions are an obstacle for vaccination. PMID- 21035826 TI - Prevalence of and risk factors for psychological distress among employees in Japan. PMID- 21035827 TI - A prospective evaluation of diagnostic methodologies for the acute diagnosis of dengue virus infection on the Thailand-Myanmar border. AB - Clinically useful diagnostic tests of dengue virus infection are lacking. We prospectively evaluated the performance of real-time reverse transcriptase (rRT) PCR, NS-1 antigen and IgM antibody tests to confirm dengue virus infection in acute blood specimens from 162 patients presenting with undifferentiated febrile illness compatible with dengue infection. rRT-PCR was the most sensitive test (89%) and potentially could be used as a single test for confirmation of dengue infection. NS-1 antigen and IgM antibody were not sufficiently sensitive to be used as a single confirmatory test with sensitivities of 54% and 17% respectively. The specificities of rRT-PCR, NS-1 antigen and IgM antibody tests were 96%, 100% and 88% respectively. Combining NS-1 and rRT-PCR or the combination of all three tests resulted in the highest sensitivity (93%) but specificities dropped to 96% and 83% respectively. We conclude that at least the combination of two tests, either agent detection (rRT-PCR) or antigen detection (NS-1) plus IgM antibody detection should be used for laboratory confirmation of dengue infection. PMID- 21035828 TI - Not just for men. AB - A 63-year-old woman developed consecutive visual loss in the presence of chronic renal failure on hemodyalisis, arterial hypertension, and pulmonary hypertension treated with sildenafil. Temporal artery biopsy was negative for giant cell arteritis. Bilateral, consecutive non-arteritic ischemic optic neuropathy was diagnosed. The implications and potential risk of sildenafil use in women are discussed. PMID- 21035829 TI - Love waves in functionally graded piezoelectric materials by stiffness matrix method. AB - A numerical matrix method relative to the propagation of ultrasonic guided waves in functionally graded piezoelectric heterostructure is given in order to make a comparative study with the respective performances of analytical methods proposed in literature. The preliminary obtained results show a good agreement, however numerical approach has the advantage of conceptual simplicity and flexibility brought about by the stiffness matrix method. The propagation behaviour of Love waves in a functionally graded piezoelectric material (FGPM) is investigated in this article. It involves a thin FGPM layer bonded perfectly to an elastic substrate. The inhomogeneous FGPM heterostructure has been stratified along the depth direction, hence each state can be considered as homogeneous and the ordinary differential equation method is applied. The obtained solutions are used to study the effect of an exponential gradient applied to physical properties. Such numerical approach allows applying different gradient variation for mechanical and electrical properties. For this case, the obtained results reveal opposite effects. The dispersive curves and phase velocities of the Love wave propagation in the layered piezoelectric film are obtained for electrical open and short cases on the free surface, respectively. The effect of gradient coefficients on coupled electromechanical factor, on the stress fields, the electrical potential and the mechanical displacement are discussed, respectively. Illustration is achieved on the well known heterostructure PZT-5H/SiO(2), the obtained results are especially useful in the design of high-performance acoustic surface devices and accurately prediction of the Love wave propagation behaviour. PMID- 21035830 TI - Sources and controls for the mobility of arsenic in oxidizing groundwaters from loess-type sediments in arid/semi-arid dry climates - evidence from the Chaco Pampean plain (Argentina). AB - In oxidizing aquifers, arsenic (As) mobilization from sediments into groundwater is controlled by pH-dependent As desorption from and dissolution of mineral phases. If climate is dry, then the process of evaporative concentration contributes further to the total concentration of dissolved As. In this paper the principal As mobility controls under these conditions have been demonstrated for Sali River alluvial basin in NW Argentina (Tucuman Province; 7000 km(2)), which is representative for other basins or areas of the predominantly semi-arid Chaco Pampean plain (1,000,000 km(2)) which is one of the world's largest regions affected by high As concentrations in groundwater. Detailed hydrogeochemical studies have been performed in the Sali River basin where 85 groundwater samples from shallow aquifers (42 samples), deep samples (26 samples) and artesian aquifers (17 samples) have been collected. Arsenic concentrations range from 11.4 to 1660 MUg L(-1) leaving 100% of the investigated waters above the provisional WHO guideline value of 10 MUg L(-1). A strong positive correlation among As, F, and V in shallow groundwaters was found. The correlations among those trace elements and U, B and Mo have less significance. High pH (up to 9.2) and high bicarbonate (HCO(3)) concentrations favour leaching from pyroclastic materials, including volcanic glass which is present to 20-25% in the loess-type aquifer sediments and yield higher trace element concentrations in groundwater from shallow aquifers compared to deep and artesian aquifers. The significant increase in minor and trace element concentrations and salinity in shallow aquifers is related to strong evaporation under semi-arid climatic conditions. Sorption of As and associated minor and trace elements (F, U, B, Mo and V) onto the surface of Fe-, Al- and Mn-oxides and oxi-hydroxides, restricts the mobilization of these elements into groundwater. Nevertheless, this does not hold in the case of the shallow unconfined groundwaters with high pH and high concentrations of potential competitors for adsorption sites (HCO(3), V, P, etc.). Under these geochemical conditions, desorption of the above mentioned anions and oxyanions occurs as a key process for As mobilization, resulting in an increase of minor and trace element concentrations. These geochemical processes that control the concentrations of dissolved As and other trace elements and which determine the groundwater quality especially in the shallow aquifers, are comparable to other areas with high As concentrations in groundwater of oxidizing aquifers and semi arid or arid climate, which are found in many parts of the world, such as the western sectors of the USA, Mexico, northern Chile, Turkey, Mongolia, central and northern China, and central and northwestern Argentina. PMID- 21035831 TI - Photodegradation of malachite green and malachite green carbinol under irradiation with different wavelength ranges. AB - The dye malachite green (MG) is used worldwide as a fungicide in aquaculture. It is a toxic substance which in aqueous solutions is partly converted into its non ionic colorless form (leucocarbinol). The equilibrium between these two forms is pH-dependent (pK=6.9). To assess the photodegradation of MG under sunlight conditions, both species were irradiated separately in aqueous solutions with different pH values (4.0 and 12.0) using various ultraviolet and visible wavelength ranges (UV/VIS). A 700 W high-pressure mercury lamp with special filters was used. No artificial photooxidizers such as H2O2 or TiO2 were added. MG leucocarbinol proved to be much more sensitive to irradiation than the dye form. Quantum yields Phi were calculated for some wavelength ranges as follows: MG carbinol: Phi((280-312 nm)) is 4.3 * 10-3, Phi((313 - 410 nm)) is 5.8 * 10-3, and MG dye: Phi((280 - 312 nm)) is 4.8 * 10(-5), Phi((313-365nm)) is 1.1*10-5, and Phi((> 365nm)) is 0, respectively. Therefore, the solar photolysis of MG is an important sink and primarily depends on the photodegradation of the colorless leucocarbinol. During the irradiation of MG leucocarbinol with wavelengths > 365 nm, an intermediate was formed which has photocatalytical properties. PMID- 21035832 TI - Effect of aging on catalytic properties in mechanochemical degradation of pentachlorophenol by birnessite. AB - Mechanochemistry, a technique concerning with milling contaminated samples for prolonged times, induces massive degradation of pollutants by grinding them in ball mills with different soil components or additives. In the present study, laboratory experiments were conducted to evaluate the effect of aging on the mechanochemical efficiency of the Mn-oxide birnessite in degrading pentachlorophenol (PCP). A comparative study on an aged birnessite (KBiA), used after 3years from synthesis, and a fresh birnessite (KBiF), employed immediately after synthesis, was carried out. The differences between the two birnessites, evidenced by spectroscopic and diffractometric techniques, are mainly relative to reduction of the Mn(IV) centered at the MnO6 octahedra layers from the birnessite structure, which represent the most reactive sites for PCP degradation. The long term air drying at room temperature, by favouring reduction of Mn(IV) to Mn(III), produces an inorganic substrate that offers paucity of the less reactive sites for PCP degradation, thus reducing the oxidative potential of the KBiA. Accordingly, the more reactive fresh birnessite was employed in the experiment with a polluted soil. Adding a small amount of KBiF to soil only induces a light increase in PCP removal, probably due to the mechanically induced PCP adsorption and transformation onto clay minerals present in the soil. Besides, adding a higher dose of birnessite causes a stronger degradation of PCP. PMID- 21035833 TI - Taphonomy and palaeoecology of the late Pleistocene to middle Holocene small mammal succession of El Harhoura 2 cave (Rabat-Temara, Morocco). AB - The relationship between local and global climatic variations and the origin and dispersal of Homo sapiens in Africa is complex, and North Africa may have played a major role in these events. In Morocco, very few studies are specifically dedicated to small fossil vertebrates, and neither taphonomic nor palaeoecological studies have been undertaken on these taxa, particularly in archaeological contexts. The late Pleistocene to middle Holocene succession of El Harhoura 2 cave, situated in the region of Temara, yields an exceptionally rich small vertebrate assemblage. We present the results of a first systematic, taphonomic, and palaeoecological study of the small mammals from Levels 1 to 8 of El Harhoura 2. The absence of bone sorting and polishing, as well as the presence of significant traces of digestion indicate that the small mammal bones were accumulated in the cave by predators and that no water transport occurred. Other traces observed on the surface of bones consist mainly of root marks and black traces (micro-organisms or more probably manganese) which affected the majority of the material. The percentage of fragmentation is very high in all stratigraphic levels, and the post-depositional breakage (geologic and anthropogenic phenomena) obscure the original breakage patterns of bones by predators. According to the ecology of the different species present in the levels of El Harhoura 2, and by taking into account possible biases highlighted by the taphonomic analysis, we reconstruct the palaeoenvironmental evolution in the region. For quantitative reconstructions we used two indices: the Taxonomic Habitat Index (THI) and the Gerbillinae/Murinae ratio. Late Pleistocene accumulations were characterised by a succession of humid (Levels 3, 4a, 6, and 8) and arid (Levels 2?, 5, and 7) periods, with more or less open landscapes, ending in an ultimate humid and wooded period during the middle Holocene (Level 1). We discuss particular limits of our results and interpretations, due to an important lack of taxonomic, ecological, and taphonomic knowledge in North Africa. PMID- 21035834 TI - Wire-mesh capped deposition sensors: novel passive tool for coarse fraction flux estimation of radon thoron progeny in indoor environments. AB - Deposition-based (222)Rn and (220)Rn progeny sensors act as unique, passive tools for determining the long time-averaged progeny deposition fluxes in the environment. The use of these deposition sensors as progeny concentration monitors was demonstrated in typical indoor environments as conceptually superior alternatives to gas-based indirect monitoring methods. In the present work, the dependency of these deposition monitors on various environmental parameters is minimized by capping the deposition sensor with a suitable wire mesh. These wire mesh capped deposition sensors measure the coarse fraction deposition flux, which is less dependent on the change in environmental parameters like ventilation rate and turbulence. The calibration of these wire-mesh capped coarse fraction progeny sensors was carried out by laboratory controlled experiments. These sensors were deployed both in indoor and in occupational environments having widely different ventilation rates. The obtained coarse fraction deposition velocities were fairly constant in these environments, which further confirmed that the signal on the wire-mesh capped sensors show the least dependency on the change in environmental parameters. This technique has the potential to serve as a passive particle sizer in the general context of nanoparticles using progeny species as surrogates. On the whole, there exists a strong case for developing a passive system that responds only to coarse fraction for providing alternative tools for dosimetry and environmental fine particle research. PMID- 21035835 TI - Determination of the bioaccessibility of chromium in Glasgow soil and the implications for human health risk assessment. AB - The Unified Bioaccessibility Method (UBM), which simulates the fluids of the human gastrointestinal tract, was used to assess the oral bioaccessibility of Cr in 27 Glasgow soils. These included several contaminated with Cr(VI), the most toxic form of Cr, from the past disposal of chromite ore processing residue (COPR). The extraction was employed in conjunction with the subsequent determination of the bioaccessible Cr by ICP-OES and Cr(VI) by the diphenylcarbazide complexation colorimetric procedure. In addition, Cr(III) containing species were determined by (i) HPLC-ICP-MS and (ii) ICP-OES analysis of gel electrophoretically separated components of colloidal and dissolved fractions from centrifugal ultrafiltration of extracts. Similar analytical procedures were applied to the determination of Cr and its species in extracts of the <10 MUm fraction of soils subjected to a simulated lung fluid test to assess the inhalation bioaccessibility of Cr. The oral bioaccessibility of Cr was typically greater by a factor of 1.5 in the 'stomach' (pH ~1.2) compared with the 'stomach+intestine' (pH ~6.3) simulation. On average, excluding two COPR contaminated soil samples, the oral bioaccessibility ('stomach') was 5% of total soil Cr and, overall, similar to the soil Cr(VI) concentration. Chromium(VI) was not detected in the extracts, a consequence of pH- and soil organic matter mediated reduction in the 'stomach' to Cr(III)-containing species, identified as predominantly Cr(III)-humic complexes. Insertion of oral bioaccessible fraction data into the SNIFFER human health risk assessment model identified site-specific assessment criteria (for residential land without plant uptake) that were exceeded by the soil total Cr (3680 mg kg(-1)) and Cr(VI) (1485 mg kg(-1)) concentration at only the most COPR-Cr(VI)-contaminated location. However, the presence of measurable Cr(VI) in the <10 MUm fraction of the two most highly Cr(VI)-contaminated soils demonstrated that inhalation of Cr(VI)-containing dust remains the most potentially harmful exposure route. PMID- 21035836 TI - Progress in the treatment of bleeding disorders. AB - The availability of plasma-derived and recombinant coagulation factors has transformed the management of patients with bleeding disorders, such as hemophilia and von Willebrand disease (VWD). However, several important clinical challenges remain that have become the focus of current research in coagulation therapy. Two prospective, non-interventional studies (HyQoL-Europe and HyQoL Canada) are evaluating the impact of major transitional life events, such as changes in social, work and living situations, on the quality of life of adolescents and young adults with hemophilia A who are treated with the recombinant factor VIII (rFVIII) concentrate Helixate(r). A better understanding of the impact of these transitional life events on quality of life may help to develop improved interventions and counseling techniques that minimize the negative effects of these events on patients with bleeding disorders. A new clinical development program has been launched to evaluate the safety and efficacy of the low-volume, highly active, plasma-derived von Willebrand factor (VWF)/FVIII concentrate Biostate(r). The program, known as SWIFT (Studies with von Willebrand factor/factor VIII) includes four clinical trials involving adult and pediatric patients with hemophilia A or VWD. Lastly, fusion of human recombinant albumin to recombinant coagulation factor IX (rFIX) has created a new fusion protein (rIX-FP) that retains the biological activity of rFIX and has a more favorable pharmacokinetic profile due to the longer half-life. The use of this novel fusion protein may offer several advantages to patients with hemophilia B: less frequent administration, prolonged protection from bleeding and improved compliance--increasing the likelihood of a positive clinical outcome. These examples of current research endeavors are intended to enhance the treatment experience as well as provide new and improved therapies for patients with bleeding disorders. PMID- 21035837 TI - A gene signature-based approach identifies thioridazine as an inhibitor of phosphatidylinositol-3'-kinase (PI3K)/AKT pathway in ovarian cancer cells. AB - OBJECTIVE: Thioridazine, a derivative of phenothiazine, has been reported to have antiproliferative activity on tumor cells. However, the mechanism has not been well defined. METHODS: Using in-silico gene signature based approach, we have demonstrated that thioridazine could inhibit phosphatidylinositol-3'-kinase (PI3K)/Akt pathway, and thus exert cytotoxicity in ovarian cancer cells. RESULTS: The Connectivity Map indicated that thioridazine induces gene signature similar to that of Akt inhibition. Moreover, preexisting inhibitors of PI3K/Akt pathway were also found to reveal similar signature. In SKOV-3 cells, immunoblot using p85 antibody showed that thioridazine could inhibit PI3K signal. In addition, thioridazine was found to inhibit p-Akt (Ser 473) in a dose-dependent manner. Furthermore, thioridazine was found to decrease cell viability and induce apoptosis. Exposure to thioridazine induced G(0)/G(1) arrest and down-regulated the cell cycle regulator, Cyclin D1 and CDK4, and up-regulated p21, p16, and p CDC25A. Finally, additive cytotoxicity was observed when cisplatin and thioridazine were treated simultaneously. CONCLUSIONS: The current study indicated that in-silico approach, such as Connectivity Map, is a potentially useful method to identify the unknown cellular function among the drugs already in use in clinic. Owing to the property of Akt inhibition and additive cytotoxicity observed with the platinum compound, further research should be focused on this drug. PMID- 21035838 TI - Ranking of elimination feasibility between malaria-endemic countries. AB - Experience gained from the Global Malaria Eradication Program (1955-72) identified a set of shared technical and operational factors that enabled some countries to successfully eliminate malaria. Spatial data for these factors were assembled for all malaria-endemic countries and combined to provide an objective, relative ranking of countries by technical, operational, and combined elimination feasibility. The analysis was done separately for Plasmodium falciparum and Plasmodium vivax, and the limitations of the approach were discussed. The relative rankings suggested that malaria elimination would be most feasible in countries in the Americas and Asia, and least feasible in countries in central and west Africa. The results differed when feasibility was measured by technical or operational factors, highlighting the different types of challenge faced by each country. The results are not intended to be prescriptive, predictive, or to provide absolute assessments of feasibility, but they do show that spatial information is available to facilitate evidence-based assessments of the relative feasibility of malaria elimination by country that can be rapidly updated. PMID- 21035839 TI - Costs and financial feasibility of malaria elimination. AB - The marginal costs and benefits of converting malaria programmes from a control to an elimination goal are central to strategic decisions, but empirical evidence is scarce. We present a conceptual framework to assess the economics of elimination and analyse a central component of that framework-potential short term to medium-term financial savings. After a review that showed a dearth of existing evidence, the net present value of elimination in five sites was calculated and compared with effective control. The probability that elimination would be cost-saving over 50 years ranged from 0% to 42%, with only one site achieving cost-savings in the base case. These findings show that financial savings should not be a primary rationale for elimination, but that elimination might still be a worthy investment if total benefits are sufficient to outweigh marginal costs. Robust research into these elimination benefits is urgently needed. PMID- 21035840 TI - Eliminating malaria--all of them. PMID- 21035841 TI - Operational strategies to achieve and maintain malaria elimination. AB - Present elimination strategies are based on recommendations derived during the Global Malaria Eradication Program of the 1960s. However, many countries considering elimination nowadays have high intrinsic transmission potential and, without the support of a regional campaign, have to deal with the constant threat of imported cases of the disease, emphasising the need to revisit the strategies on which contemporary elimination programmes are based. To eliminate malaria, programmes need to concentrate on identification and elimination of foci of infections through both passive and active methods of case detection. This approach needs appropriate treatment of both clinical cases and asymptomatic infections, combined with targeted vector control. Draining of infectious pools entirely will not be sufficient since they could be replenished by imported malaria. Elimination will thus additionally need identification and treatment of incoming infections before they lead to transmission, or, more realistically, embarking on regional initiatives to dry up importation at its source. PMID- 21035843 TI - Research priorities for malaria elimination. PMID- 21035842 TI - Shrinking the malaria map: progress and prospects. AB - In the past 150 years, roughly half of the countries in the world eliminated malaria. Nowadays, there are 99 endemic countries-67 are controlling malaria and 32 are pursuing an elimination strategy. This four-part Series presents evidence about the technical, operational, and financial dimensions of malaria elimination. The first paper in this Series reviews definitions of elimination and the state that precedes it: controlled low-endemic malaria. Feasibility assessments are described as a crucial step for a country transitioning from controlled low-endemic malaria to elimination. Characteristics of the 32 malaria eliminating countries are presented, and contrasted with countries that pursued elimination in the past. Challenges and risks of elimination are presented, including Plasmodium vivax, resistance in the parasite and mosquito populations, and potential resurgence if investment and vigilance decrease. The benefits of elimination are outlined, specifically elimination as a regional and global public good. Priorities for the next decade are described. PMID- 21035844 TI - Call to action: priorities for malaria elimination. PMID- 21035845 TI - Malaria elimination: worthy, challenging, and just possible. PMID- 21035846 TI - The effect of biodegradable gelatin microspheres on the neuroprotective effects of high mobility group box 1 A box in the postischemic brain. AB - High mobility group box 1 (HMGB1) is a family of endogenous molecules that is released by necrotic cells and causes neuronal damages by triggering inflammatory processes. In the cerebral ischemic brain, sustained and regulated suppression of HMGB1 has been emerged as a therapeutic means to grant neuroprotection. HMGB1 consists of two HMG boxes (A and B) and an acidic C-terminal tail, and the A box peptide antagonistically competes with HMGB1 for its receptors. In the middle cerebral artery occlusion (MCAO) in rats, a murine model of transient cerebral ischemia, administration of HMGB1 A box intraparenchymally, after encapsulated in biodegradable gelatin microspheres (GMS), which enhances the stability of peptide inside and allows its sustained delivery, at 1 h, 3 h, or 6 h after MCAO, reduced mean infarct volumes by, respectively, 81.3%, 42.6% and 30.7% of the untreated MCAO-brain, along with remarkable improvement of neurological deficits. Furthermore, the administration of HMGB1 A box/GMS suppressed proinflammatory cytokine inductions more strongly than the injection of non-encapsulated HMGB1 A box. Given that insulted brains-like ischemia have enhanced gelatinase activity than the normal brain, our results suggest that GMS-mediated delivery of therapeutic peptides is a promising means to provide efficient neuroprotection in the postischemic brain. PMID- 21035847 TI - Pathologic basis of echogenic cystic lesions in the human placenta: role of ultrasound-guided wire localization. AB - OBJECTIVE: The sonographic appearance of the placenta is normally homogenous throughout the second trimester. A variety of abnormalities in placental texture have been described, some of which may be pathologic and associated with adverse clinical outcomes. We characterized the pathologic basis of one lesion termed echogenic cystic lesions (ECLs) that may be a prognostic marker in intrauterine growth restriction (IUGR). STUDY DESIGN: We retrospectively correlated placental pathology in 50 pregnancies that had a total of 84 ECLs documented by ultrasound prior to delivery. Six additional women with placental ECLs prospectively underwent immediate post-delivery ultrasound-guided wire localization of 9 lesions followed by placental pathology. Obstetric outcome data were recorded. RESULTS: Severe pre-eclampsia (20%) and extreme IUGR (18%) were common outcomes. Of 93 ECLs identified, 46 (49%) gross lesions were found by placental pathology. Inter-villous thrombosis was the most significant lesion found (30/46, 65%) compared to all other lesions (35%; Z-Test, p = 0.007). Ultrasound guidance identified 8/9 (89%) lesions of which 6/8 (67%) were inter-villous thrombosis. Associated lesions (infarction, 36%; advanced villous maturation, 27%) and small placental weight (<10th centile, 38%) were present in 50%, but did not increase the risk of adverse perinatal outcome. CONCLUSIONS: ECLs are most commonly due to inter-villous thrombosis. The adverse clinical outcomes may be mediated by associated lesions not readily detectable by ultrasound. Ultrasound-guided wire localization is a promising research tool for future large-scale cohort studies needed to define the clinical utility of placental ultrasound findings. PMID- 21035848 TI - Inhibition of HTRA3 stimulates trophoblast invasion during human placental development. AB - Controlled invasion of extravillous trophoblast (EVT) is necessary for implantation and placentation. The serine protease HTRA3 is highly expressed in decidual cells in the late secretory phase of the menstrual cycle and throughout pregnancy. During the first trimester it is expressed in most trophoblast cell types, but not in the invading interstitial trophoblast. HTRA3 and its family members are down-regulated in a number of cancers and are proposed as tumour suppressors. The current study investigated whether inhibiting HTRA3 in a first trimester trophoblast cell line expressing high levels of HTRA3 would alter invasion. HTR-8/SVneo (HTR-8, derived from first trimester placenta) and a number of choriocarcinoma cells (JEG-3, AC-1M88 and AC-1M32) were screened for HTRA3 expression. Only HTR-8 cells expressed high levels of HTRA3 mRNA, consistent with HTRA3 being down-regulated in cancer. Western blotting and immunofluorescence confirmed HTRA3 protein expression and localisation in HTR-8 cells. HTRA3 was detected in conditioned medium of HTR-8 cells, confirming its secretory nature. For functional studies, both long and short forms of recombinant human HTRA3, wild type and protease-inactive mutant (S(305)A) were produced using wheat-germ cell-free technology. Both have a similar molecular size, but the mutants have negligible protease activity. In addition, the mutants significantly inhibited the wild type protease activity, supporting their dominant-negative inhibition and utility as specific inhibitors of the wild type protein. Inhibition of HTRA3 by exogenous addition of HTRA3 mutant resulted in a significant increase in HTR-8 cell invasion. These results strongly support the hypothesis that HTRA3 is an inhibitor of trophoblast invasion during placental development. PMID- 21035849 TI - Chronic intervillositis of the placenta: a systematic review. AB - OBJECTIVE: Chronic intervillositis of the placenta is known to be associated with poor reproductive outcome and a high risk of recurrence. The aims of the present study were to quantify the risk of recurrence of chronic intervillositis in subsequent pregnancies, to explore if there are possible interventions and to assess the success of interventions. METHODS: Systematic review of published literature using published guidelines. RESULTS: No randomised controlled trials were identified. Sixty-one papers, published between 1977 and 2009 were identified after abstract screening but only 6 studies could be included in the systematic review. From the 6 selected studies, 69 pregnancies at gestational age of 14 weeks or over, with a histopathologic diagnosis of chronic intervillositis were available for analysis. The rate of intrauterine growth restriction in the study population was 66.7%, the overall rate of livebirth was 53.6%. In 16/20 (80.0%) cases recurrence of CI was confirmed at histopathology. The livebirth rate reported with treatment was 30.8% against 58.9% without treatment (RR=0.47, 95% CI=0.2-1.1). This difference was not statistically significant. CONCLUSIONS: Chronic intervillositis has a high (80.0%) recurrence risk. In pregnancies reaching 14 weeks, the chance of a livebirth is 53.6%. The livebirth rate reported with treatment was 30.8% against 58.9% without treatment (RR=0.47, 95% CI=0.2-1.1). This difference was not statistically significant. Intervention with drug therapy is of no demonstrable benefit, and may even be harmful. PMID- 21035850 TI - Treatment with low-dose aspirin increased the level LIF and integrin beta3 expression in mice during the implantation window. AB - Embryo implantation is the group of processes by which the developing blastocyst adheres to, and embeds into, the receptive endometrium. Changes in the expression of molecules on the cell surface have been seen in the conversion of the endometrial surface from a non-receptive to a receptive state. Cell adhesion molecules like integrins, or soluble factors such as Leukemia inhibitory factor (LIF) have been identified to play an important role during the implantation period. Studies have suggested that low-dose aspirin (<100 mg/d) treatment can improve implantation rate, ovarian responsiveness, and pregnant rates in IVF patients. The mechanism of this increased implantation rate is unclear, and in this study we hypothesised that the expression of integrin beta3 or LIF may be altered, during implantation window, by treatment with low-dose aspirin. Female mice were treated with 0.9 mg/ml aspirin daily for 15 days and then were mated. The protein or mRNA levels of LIF and integrin beta3 in the endmetrium were determined on the day 4 post-coitus using immuno-fluorescence and RT-PCR. We found the expression of LIF or integrin beta3 was significantly increased in the endometrium of mice that were treated with low dose of aspirin by immuno fluorescence. In addition, the mRNA level of LIF or integrin beta3 on the endometrium of aspirin treated mice was also significantly increased compared to untreated mice. We conclude that low dose aspirin alters the expression of endometrial LIF and integrin beta3 and that these changes may increase endometrial receptivity. PMID- 21035852 TI - Stretch-activated channels in pulmonary arterial smooth muscle cells from normoxic and chronically hypoxic rats. AB - Stretch-activated channels (SACs) act as membrane mechanotransducers since they convert physical forces into biological signals and hence into a cell response. Pulmonary arterial smooth muscle cells (PASMCs) are continuously exposed to mechanical stimulations e.g., compression and stretch, that are enhanced under conditions of pulmonary arterial hypertension (PAH). Using the patch-clamp technique (cell-attached configuration) in PASMCs, we showed that applying graded negative pressures (from 0 to -60 mmHg) to the back end of the patch pipette increases occurrence and activity of SACs. The current-voltage relationship (from -80 to +40 mV) was almost linear with a reversal potential of 1 mV and a slope conductance of 34 pS. SACs were inhibited in the presence of GsMTx-4, a specific SACs blocker. Using microspectrofluorimetry (indo-1), we found that hypotonic induced cell swelling increases intracellular Ca(2+) concentration ([Ca(2+)](i)). This [Ca(2+)](i) increase was markedly inhibited in the absence of external Ca(2+) or in the presence of the following blockers of SACs: gadolinium, streptomycin, and GsMTx-4. Interestingly, in chronically hypoxic rats, an animal model of PAH, SACs were more active and hypotonic-induced calcium response in PASMCs was significantly higher (nearly a two-fold increase). Moreover, unlike in normoxic rats, intrapulmonary artery rings from hypoxic rats mounted in a Mulvany myograph, exhibited a myogenic tone sensitive to SAC blockers. In conclusion, this work demonstrates that SACs in rat PASMCs can be activated by membrane stretch as well as hypotonic stimulation and are responsible for [Ca(2+)](i) increase. The link between SACs activation-induced calcium response and myogenic tone in chronically hypoxic rats suggests that SACs are an important element for the increased pulmonary vascular tone in PAH and that they may represent a molecular target for PAH treatment. PMID- 21035851 TI - A helix-breaking mutation in the epithelial Ca(2+) channel TRPV5 leads to reduced Ca(2+)-dependent inactivation. AB - TRPV5, a member of transient receptor potential (TRP) superfamily of ion channels, plays a crucial role in epithelial calcium transport in the kidney. This channel has a high selectivity for Ca(2+) and is tightly regulated by intracellular Ca(2+) concentrations. Recently it was shown that the molecular basis of deafness in varitint-waddler mouse is the result of hair cell death caused by the constitutive activity of transient receptor potential mucolipin 3 (TRPML3) channel carrying a helix breaking mutation, A419P, at the intracellular proximity of the fifth transmembrane domain (TM5). This mutation significantly elevates intracellular Ca(2+) concentration and causes rapid cell death. Here we show that substituting the equivalent location in TRPV5, the M490, to proline significantly modulates Ca(2+)-dependent inactivation of TRPV5. The single channel conductance, time constant of inactivation (tau) and half maximal inhibition constant (IC(50)) of TRPV5(M490P) were increased compared to TRPV5(WT). Moreover TRPV5(M490P) showed lower Ca(2+) permeability. Out of different point mutations created to characterize the importance of M490 in Ca(2+)-dependent inactivation, only TRPV5(M490P)-expressing cells showed apoptosis and extremely altered Ca(2+)-dependent inactivation. In conclusion, the TRPV5 channel is susceptible for helix breaking mutations and the proximal intracellular region of TM5 of this channel plays an important role in Ca(2+) dependent inactivation. PMID- 21035853 TI - Quantitative evaluation of p16(INK4a) promoter methylation using pyrosequencing in de novo diffuse large B-cell lymphoma. AB - The p16(INK4a) tumor suppressor gene can be inactivated by a variety of events including promoter hypermethylation. In diffuse large B-cell lymphoma (DLBCL), p16(INK4a) methylation has been associated with advanced disease stage and higher IPI. The prognostic impact of p16(INK4a) methylation in DLBCL remains unclear; however, it has been suggested to correlate with inferior outcome. To further investigate the clinical impact of p16(INK4a) methylation in DLBCL, promoter methylation of this gene was assessed quantitatively by pyrosequencing. Forty-two of 113 (37%) DLBCL patients with methylation level above 5% were categorized as methylated and subsequently divided into low, intermediate and high methylation categories. Overall, no association was shown between the extent of p16(INK4a) methylation and patients' clinical characteristics, except disease stage (P=0.049). Moreover, we could not reveal any impact of p16(INK4a) methylation on lymphoma-specific survival. Although >25% of p16(INK4a) methylation correlated with a better progression-free survival (P=0.048) in patients <65 years old, the significance of this finding, if any, needs to be further investigated. In conclusion, our finding questions the role of p16(INK4a) promoter methylation as a negative prognostic factor in DLBCL. PMID- 21035855 TI - Making the right conclusions based on wrong results and small sample sizes: interpretation of statistical tests in ecotoxicology. AB - In environmental risk assessments statistical tests are a standard tool to evaluate the significance of effects by pesticides. While it has rarely been assessed how likely it is to detect effects given a specific sample size, it was never analysed how reliable results are if the test preconditions, particularly of parametric tests, are not fulfilled or how likely it is to detect deviations from these preconditions. Therefore, we analyse the performance of a parametric and a non-parametric test using Monte Carlo simulation, focussing on typical data used in ecotoxicological risk assessments. We show that none of the data distributions are normal and that for typical sample sizes of N<20 it is very unlikely to detect deviations from normality. Non-parametric tests performed markedly better than parametric tests, except when data were in fact normally distributed. We finally discuss the impact of using different tests on pesticide risk assessments. PMID- 21035854 TI - CDDO-Im is a stimulator of megakaryocytic differentiation. AB - Although the triterpene CDDO and its potent derivatives, CDDO-Im and CDDO-Me, are now in phase I/II studies in the treatment of some pathological conditions, their effects on normal hematopoiesis are not known. In the present study we provide evidence that CDDO-Im exerts in vitro a potent inhibitory effect on erythroid cell proliferation and survival and a stimulatory action on megakaryocytic differentiation. The effect of CDDO-Im on erythroid and megakaryocytic differentiation was evaluated both on normal hemopoietic progenitor cells (HPCs) induced to selective erythroid (E) or megakaryocytic (Mk) differentiation and on erythroleukemic cell lines HEL and TF1. The inhibitory effect of CDDO-Im on erythroid cell survival and proliferation is mainly related to a reduced GATA-1 expression. This conclusion is supported by the observation that GATA-1 overexpressing TF1 cells are partially protected from the inhibitory effect of CDDO-Im on cell proliferation and survival. The stimulatory effect of CDDO-Im on normal megakaryopoiesis is seemingly related to upmodulation of GATA2 expression and induction of mitogen-activated protein kinases ERK1/2. PMID- 21035856 TI - Effects of nanosized titanium dioxide on innate immune system of fathead minnow (Pimephales promelas Rafinesque, 1820). AB - Effects of nanosized (<100 nm) titanium dioxide (TiO(2)) particles on fish neutrophils and immune gene expression was investigated using the fathead minnow (Pimpehales promelas). Expanded use of TiO(2) in the cosmetic industry has increased the potential exposure risk to aquatic ecosystems and human health. Effects of nano-TiO(2) on neutrophil function of the fathead minnow was investigated using oxidative burst, neutrophil extracellular traps (NETs) release and degranulation of primary granules. The innate immune gene expression was determined with quantitative PCR (qPCR). Application of 0.1 MUg mL(-1) of nano TiO(2) in vitro stimulated oxidative burst and NET release. Intraperitoneal injection of 10 MUg g(-1) of nano-TiO(2) caused a significant decrease in oxidative burst, NETs release and degranulation (21%; 11%; and 30%, decrease, respectively). Fish exposed to nano-TiO(2) for 48 h in vivo had significantly increased expression of interleukin 11, macrophage stimulating factor 1, and neutrophil cytosolic factor 2 (4; 2.5; and 2 fold increase, respectively). Nano TiO(2) has potential to interfere with the evolutionary conserved innate immune system responses, as evidenced with observed changes in gene expression and neutrophil function. This finding encourages the use of fish models in the studies of nanoparticle immunotoxicity. The lowest significant response concentration studied in vitro is four times greater than the estimated environmental concentration for TiO(2) (0.025 MUg mL(-1)) causing concern about potential impact of nano-TiO(2) on aquatic animals and ecosystems. PMID- 21035857 TI - Deleterious effects in mice of fish-associated methylmercury contained in a diet mimicking the Western populations' average fish consumption. AB - Methylmercury (MeHg) is a potent neurotoxin, and human beings are mainly exposed to this pollutant through fish consumption. Only a few contradictory epidemiological studies are currently available examining the impact of fish consumption on human populations. In the present study, we wanted to address whether a diet mimicking the fish consumption of Western populations could result in observable adverse effects in mice, and whether beneficial nutriments from fish were able to counterbalance the deleterious effects of MeHg, if any. In Europe and the United States, fish consumption varies widely between countries, from 11 to 100 g fish/day. A mid-range value of 25 g fish/day corresponds to a fish contribution to the total diet of 1.25% on a dry weight basis. We decided to supplement a vegetarian-based mouse diet with 1.25% of lyophilized salmon flesh (SAL diet), or 1.25% of a blend of lyophilized cod, tuna, and swordfish (CTS diet). Total mercury contents were 1.15+/-0.15, 2.3+/-0.1 and 35.75+/-0.15 ng Hg/g of food pellets for the control, SAL and CTS diets, respectively. After two months feeding, the CTS diet resulted in significant observable effects as compared to the control and SAL diets, encompassing decreased body growth, altered behavioral performance and increased anxiety level, modification of mitochondrial respiratory protein subunit concentrations in kidney and brain structures, modified gene expression patterns in kidneys, liver and muscles, and a decrease of dopamine concentrations in the hypothalamus and striatum. Our findings have health implications, firstly because 1.25% of CTS flesh in the diet corresponds to an average exposure to MeHg below the WHO provisory tolerable weekly intake (PTWI) (1.6 MUg MeHg/kg of body weight/week), and secondly because many people in Western populations, among them women of child-bearing age, are exceeding the PTWI value (for instance, 35% of the French population inhabiting the Atlantic and Mediterranean coasts). PMID- 21035858 TI - Role of interleukin-18 in human natural killer cell is associated with interleukin-2. AB - Human natural killer (NK) cells constitute an important cellular component of innate immunity, capable of killing infected and transformed cells. The proliferation and activation of NK cells are regulated by various cytokines. Interleukin-18 (IL-18) promotes NK cell activation; however, whether the effects of IL-18 on NK cell are associated with other cytokines is still unknown. In this study, we observed that IL-18 induced NK cell apoptosis and inhibited NK cell expansion in the presence of low concentrations of interleukin-2 (IL-2), while high concentrations of IL-2 overcame these effects of IL-18, and high concentrations of IL-2 promoted the stimulatory activity of IL-18 on NK cells. At a low concentration of IL-2, IL-18 induced NK cell apoptosis in part through activation of the FasL/Fas- and TNFalpha/TNFR-mediated death receptor signaling by enhancing FasL expression and inhibiting c-FLIP(long) expression. However, high concentrations of IL-2 strongly blocked IL-18-induced NK cell apoptosis through alleviating IL-18-induced FasL expression and activation of Fas-mediated death signaling and increasing anti-apoptosis molecule (Bcl-X(L)). These results reveal that the effects of IL-18 on human NK cell are associated with IL-2 concentration and suggest the importance of IL-2 level in cytokine immunotherapy. PMID- 21035859 TI - Comparison of femtosecond laser-assisted keratoplasty versus conventional penetrating keratoplasty. AB - PURPOSE: To compare postoperative outcomes for femtosecond laser-assisted keratoplasty (FLAK) with conventional penetrating keratoplasty (PK). DESIGN: Retrospective, comparative surgical series. PARTICIPANTS: Fifty consecutive patients who underwent FLAK and 50 case-controlled patients that had PK at the Casey Eye Institute (Oregon Health & Science University, Portland, OR). METHODS: Data was collected for 50 consecutive cases that underwent zigzag incision FLAK and was compared with 50 subjects that had conventional blade trephine incision PK with similar age, diagnosis and concurrent ocular morbidities over a 2-year follow-up period. MAIN OUTCOME MEASURES: Topographic astigmatism, best spectacle corrected visual acuity, uncorrected visual acuity, pinhole visual acuity, and the timing of selective suture removal (or adjustment) over various follow-up intervals up to 2 years postoperatively. RESULTS: Significantly lower topographic astigmatism was achieved in the FLAK group over the PK group in the 4- to 6-month follow-up period (P = 0.0324), which correlated well with significant earlier selective suture removal that occurred in that same group over both the 2- to 3 month (P = 0.0025) and 4- to 6-month (P = 0.0236) follow-up periods. This difference in astigmatism was no longer present at any other follow-up period up to 24 months postoperatively. The subset analysis of patients with keratoconus or post-LASIK ectasia did not show any difference in either astigmatism or visual acuity at any time. CONCLUSIONS: Compared with PKP, FLAK had significant improvement in astigmatism before but not after the 6 month postoperative follow up period. Earlier suture removal was noted in the FLAK group. No significant improvement in best spectacle-corrected visual acuity was noted at any time point. There were no complications or difficulties with trephination in the FLAK procedure across a wide range of corneal pathologies. PMID- 21035860 TI - Ocular findings in patients with polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes syndrome. AB - OBJECTIVE: Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome is a rare disorder. This study investigated the types of ocular signs and symptoms in patients with POEMS and any systemic factors that may be associated with development of such ocular findings. DESIGN: Case series from tertiary referral center. PARTICIPANTS: A total of 33 patients with POEMS syndrome underwent at least 1 ophthalmologic examination and were included in the study. METHODS: A 10-year retrospective chart review of patients diagnosed with POEMS syndrome was performed. MAIN OUTCOME MEASURES: Visual symptoms, visual acuity, presence of optic disc edema (ODE), and levels of systemic factors (including plasma vascular endothelial growth factor [VEGF], plasma interlukin-6 [IL-6], and raised intracranial pressure) and their relationship to ODE. RESULTS: Five of the patients (15%) reported diplopia, 15 patients (45%) had blurred vision, and 3 patients (9%) had ocular pain. The most common ocular finding was bilateral ODE in 17 patients (52%). Of the patients with ODE, 5 (29%) were asymptomatic at the first ocular examination. Among patients with ODE, there was a significant difference (P = 0.03) between the mean plasma VEGF level at the time of diagnosis of the ODE compared with when the ODE resolved. There was no difference in plasma IL-6 levels between people with and without ODE. Patients with ODE had a higher mean lumbar puncture opening pressure (276+/-14 mm H(2)O; normal range, 100-250 mm H(2)0) than patients without ODE, although the difference was not statistically significant (P = 0.08). CONCLUSIONS: Optic disc edema is a common finding in patients with POEMS. Because patients can be asymptomatic, eye examinations should be performed in all patients with POEMS. There may be an association between elevated VEGF and intracranial pressure and ODE; further studies are required. PMID- 21035861 TI - Progression of geographic atrophy in age-related macular degeneration imaged with spectral domain optical coherence tomography. AB - PURPOSE: To determine the area and enlargement rate (ER) of geographic atrophy (GA) in patients with age-related macular degeneration (AMD) using the spectral domain optical coherence tomography (SD-OCT) fundus image. DESIGN: Prospective, longitudinal, natural history study. PARTICIPANTS: Eighty-six eyes of 64 patients with >=6 months of follow-up. METHODS: Patients with GA secondary to AMD were enrolled in this study. Macular scans were performed using the Cirrus SD-OCT (Carl Zeiss Meditec, Dublin, CA). The areas of GA identified on the SD-OCT fundus images were quantified using a digitizing tablet. Reproducibility of these measurements was assessed and the ER of GA was calculated. The usefulness of performing square root transformations of the lesion area measurements was explored. MAIN OUTCOME MEASURES: Enlargement rate of GA. RESULTS: At baseline, 27% of eyes had a single area of GA. The mean total area at baseline was 4.59 mm(2) (1.8 disc areas [DA]). The mean follow-up time was 1.24 years. Reproducibility, as assessed with the intraclass correlation coefficient (ICC), was excellent on both the original area scale (ICC = 0.995) and the square root scale (ICC = 0.996). Intergrader differences were not an important source of variability in lesion size measurement (ICC = 0.999, 0.997). On average, the ER of GA per year was 1.2 mm(2) (0.47 DA; range, 0.01-3.62 mm(2)/year). The ER correlated with the initial area of GA (r = 0.45; P<0.001), but there were variable growth rates for any given baseline area. When the square root transformation of the lesion area measurements was used as a measure of lesion size, the ER (0.28 mm/yr) was not correlated with baseline size (r = -0.09; P = 0.40). In this cohort of lesions, no correlation was found between ER and length of follow-up. Square root transformation of the data helped to facilitate sample size estimates for controlled clinical trials involving GA. CONCLUSIONS: The SD OCT fundus image can be used to visualize and quantify GA. Advantages of this approach include the convenience and assurance of using a single imaging technique that permits simultaneous visualization of GA along with the loss of photoreceptors and the retinal pigment epithelium that should correlate with the loss of visual function. PMID- 21035862 TI - Descemet's stripping endothelial keratoplasty five-year graft survival and endothelial cell loss. AB - PURPOSE: To assess 5-year Descemet's stripping endothelial keratoplasty (DSEK) graft survival and endothelial cell loss in the surviving grafts. DESIGN: Retrospective, interventional case series. PARTICIPANTS: One hundred sixty-five eyes of 149 patients treated with primary DSEK. METHODS: Donor corneal-scleral rims were dissected manually or with a microkeratome and were cut with a trephine. The graft was folded endothelial side inward and was inserted with forceps through a 5-mm incision. The cumulative probability of secondary graft failure was calculated using Kaplan-Meier survival analysis and the log-rank test. Endothelial cell density (ECD) was determined from baseline preoperative donor and 1-year, 3-year, and 5-year postoperative central endothelial images. MAIN OUTCOME MEASURES: Graft survival and ECD at 5 years. RESULTS: The median recipient age was 71 years (range, 22-90 years) and 62% were female. Eighteen eyes (11%) were treated for pseudophakic or aphakic corneal edema and 147 eyes (89%) were treated for Fuchs' dystrophy. The cumulative 5-year survival rate was significantly lower in pseudophakic or aphakic corneal edema eyes (76%) versus Fuchs' eyes (95%; P = 0.0087). In particular, the 5-year survival rate was reduced significantly in eyes with prior glaucoma shunt or trabeculectomy surgery vs. those without (40% vs. 95%; P<0.0001). The causes of secondary graft failure were endothelial decompensation in 6 eyes (3.6%) and unsatisfactory corrected distance acuity (20/60 to 20/100) in 4 eyes (2.4%). No grafts experienced traumatic wound rupture or failed as a result of ocular surface complications. The median 5-year endothelial cell loss was 53% (range, 7.5%-89%). The 5-year graft ECD was correlated weakly with the baseline donor ECD (r = 0.22 and P = 0.04) and was not significantly correlated with recipient gender (P = 0.075), age (P = 0.85), or diagnosis (P = 0.78). CONCLUSIONS: The 5-year graft survival rates for DSEK were similar to those reported for penetrating keratoplasty in the multicenter Cornea Donor Study (95% vs. 93% for Fuchs' dystrophy and 76% vs. 73% for pseudophakic or aphakic corneal edema). Furthermore, the 5-year endothelial cell loss after DSEK compared favorably with that measured after penetrating keratoplasty in the Cornea Donor Study (53% vs. 70%). PMID- 21035863 TI - Prevalence and risk factors for epiretinal membranes in a multi-ethnic United States population. AB - PURPOSE: To describe the prevalence of and risk factors for epiretinal membrane (ERM) in a multi-ethnic population and to evaluate possible racial or ethnic differences. DESIGN: Cross-sectional study. PARTICIPANTS: Participants of the Multi-Ethnic Study of Atherosclerosis (MESA), examined at the second visit of the MESA when retinal photography was performed. METHODS: Data on 5960 participants aged 45 to 84 years from MESA, including white, black, Hispanic, and Chinese persons from 6 United States communities, were analyzed. Epiretinal membrane was assessed from digital nonstereoscopic fundus photographs and was defined as cellophane macular reflex (CMR) without retinal folds or preretinal macular fibrosis (PMF) with retinal folds. Risk factors were assessed from standardized interviews, clinical examinations, and laboratory investigations. MAIN OUTCOME MEASURES: Epiretinal membrane prevalence by ethnic or racial group and risk factors associated with ERM. RESULTS: The prevalence of any ERM was 28.9%, of which 25.1% were CMR cases and 3.8% were PMF cases. The prevalence of ERM was significantly higher in Chinese persons (39.0%), compared with Hispanic (29.3%), white (27.5%), or black (26.2%; P<0.001) persons. In multivariate models, increasing age (odds ratio [OR], 1.19; 95% confidence interval [CI], 1.06-1.34, per year increase in age), diabetes (OR, 1.92; 95% CI, 1.39-2.65), and hypercholesterolemia (OR, 1.33; 95% CI, 1.04-1.69) were significantly associated with CMR. CONCLUSIONS: This study showed that ERM was significantly more common in Chinese persons compared with whites, blacks, and Hispanics. Risk factors for ERM were increasing age, presence of diabetes, and hypercholesterolemia. PMID- 21035864 TI - Lens vault, thickness, and position in Chinese subjects with angle closure. AB - PURPOSE: To investigate the association of lens parameters-specifically, lens vault (LV), lens thickness (LT), and lens position (LP)-with angle closure. DESIGN: Prospective, comparative study. PARTICIPANTS: One hundred two Chinese subjects with angle closure (consisting of primary angle closure, primary angle closure glaucoma, and previous acute primary angle closure) attending a glaucoma clinic and 176 normal Chinese subjects with open angles and no evidence of glaucoma recruited from an ongoing population-based cross-sectional study. METHODS: All participants underwent gonioscopy and anterior-segment optical coherence tomography (AS OCT; Carl Zeiss Meditec, Dublin, CA). Customized software was used to measure LV, defined as the perpendicular distance between the anterior pole of the crystalline lens and the horizontal line joining the 2 scleral spurs, on horizontal AS OCT scans. A-scan biometry (US-800; Nidek Co, Ltd, Tokyo, Japan) was used to measures LT and to calculate LP (defined as anterior chamber depth [ACD] +1/2 LT) and relative LP (RLP; defined as LP/axial length [AL]). MAIN OUTCOME MEASURES: Lens parameters and angle closure. RESULTS: Significant differences between angle-closure and normal eyes were found for LV (901+/-265 vs. 316+/-272 MUm; P<0.001), LT (4.20+/-0.92 vs. 3.90+/-0.73 mm; P = 0.01), LT-to-AL ratio (0.18+/-0.04 vs. 0.16+/-0.03; P<0.001), ACD (2.66+/-0.37 vs. 2.95+/-0.37 mm; P<0.001), and AL (22.86+/-0.93 vs. 23.92+/-1.37 mm; P<0.001), but no significant differences were found for LP (4.76+/-0.51 vs. 4.90+/-0.54 mm; P = 0.34) or RLP (0.21+/-0.02 vs. 0.20+/-0.02; P = 0.14). After adjusting for age, gender, ACD, LT, and RLP, increased LV was associated significantly with angle closure (odds ratio [OR], 48.1; 95% confidence interval [CI], 12.8-181.3, comparing lowest to highest quartile), but no association was found for LT (OR, 1.78; 95% CI, 0.76-4.16), LP (OR, 1.94; 95% CI, 0.59-6.31), or RLP (OR, 2.08; 95% CI, 0.66-6.57). There was low correlation between LV and LT (Pearson's correlation coefficient [PCC], 0.17), between LV and RLP (PCC, 0.08), or between LV and LP (PCC, 0.2). CONCLUSIONS: Eyes with angle closure have thicker lenses with greater LV compared with normal eyes. The LV, which represents the anterior portion of the lens, is a novel parameter independently associated with angle closure after adjusting for age, gender, ACD, and LT. PMID- 21035865 TI - Diagnosis of intravascular lymphoma by a novel biopsy site. AB - PURPOSE: To report the first known case of intravascular lymphoma (IVL), a rare disease, diagnosed via lacrimal gland biopsy. DESIGN: Interventional case report. PARTICIPANTS: Single patient case report. INTERVENTION: Bedside lacrimal gland biopsy. MAIN OUTCOME MEASURES: Clinicopathologic diagnosis of IVL, a neoplasm with only a few prior reports of ophthalmic manifestations, via a novel biopsy site. RESULTS: A 70-year-old Chinese man with 6 months of progressive paraplegia complained of blurred vision in both eyes. He had unremarkable cerebrospinal fluid studies and magnetic resonance imaging that showed abnormal thoracic cord signal and periventricular brain white matter changes with a normal pituitary gland and stalk. Dilated fundus examination showed multifocal areas of intra- and subretinal hemorrhage with serous retinal detachment. The workup included serologies and 2 normal bone marrow biopsies but did not reveal the underlying etiology. Because of the continued high suspicion for a malignant process, we performed bedside transconjunctival biopsy of the lacrimal gland. This demonstrated large, atypical CD20-positive B cells confined to the vessel lumina, consistent with IVL, an unusual form of large B-cell lymphoma. CONCLUSIONS: This case represents the first time that IVL has been detected via lacrimal gland biopsy, which may be a useful way to investigate cryptogenic neurologic processes. Furthermore, it is one of the only reported cases of ophthalmic IVL diagnosed before autopsy. IVL is a rare disease but has protean manifestations involving the central nervous system, skin, bone marrow, liver, and spleen. The eye should also be considered an end organ for involvement. PMID- 21035866 TI - YAG laser peripheral iridotomy for the prevention of pigment dispersion glaucoma a prospective, randomized, controlled trial. AB - PURPOSE: To test the hypothesis that neodymium:yttrium-aluminum-garnet (Nd:YAG) laser peripheral iridotomy (LPI) significantly reduces the incidence of conversion from pigment dispersion syndrome (PDS) with ocular hypertension (OHT) to pigmentary glaucoma (PG). DESIGN: Prospective, randomized, controlled 3-year trial. PARTICIPANTS: One hundred sixteen eyes of 116 patients with PDS and OHT. INTERVENTION: Patients were assigned randomly either to Nd:YAG LPI or to a control group (no laser). MAIN OUTCOME MEASURES: The primary outcome measure was conversion to PG within 3 years, based on full-threshold visual field (VF) analysis using the Ocular Hypertension Treatment Study criteria. Secondary outcome measures were whether eyes required topical antiglaucoma medications during the study period and the time to conversion or medication. RESULTS: Fifty seven patients were randomized to undergo laser treatment and 59 were randomized to no laser (controls). Age, gender, spherical equivalent refraction, and intraocular pressure at baseline were similar between groups. Outcome data were available for 105 (90%) of recruited subjects, 52 in the laser treatment group and 53 in the no laser treatment group. Patients were followed up for a median of 35.9 months (range, 10-36 months) in the laser arm and 35.9 months (range, 1-36 months) in the control arm. Eight eyes (15%) in the laser group and 3 eyes (6%) in the control group converted to glaucoma in the study period. The proportion of eyes started on medical treatment was similar in the 2 groups: 8 eyes (15%) in the laser group and 9 eyes (17%) in the control group. Survival analyses showed no evidence of any difference in time to VF progression or commencement of topical therapy between the 2 groups. Cataract extraction was performed on 1 patient in the laser group and in 1 patient in the control group during the study period (laser eye at 18 months; control eye at 34 months). CONCLUSIONS: This study suggests that there was no benefit of Nd:YAG LPI in preventing progression from PDS with OHT to PG within 3 years of follow-up. PMID- 21035867 TI - Kjellin syndrome: long-term neuro-ophthalmologic follow-up and novel mutations in the SPG11 gene. AB - OBJECTIVE: Kjellin's syndrome is a hereditary neuro-ophthalmologic syndrome. We describe the clinical phenotypes of 7 patients, identifying the responsible mutations for 4 of them. A 10-year ophthalmologic and neurologic follow-up of 5 patients allowed us to describe the disease's characteristics, early symptoms and progression, associated ocular signs, and retinal changes in carriers. DESIGN: Retrospective clinical study and molecular genetics investigation. PARTICIPANTS: The records of 7 patients with Kjellin's syndrome were analyzed retrospectively. METHODS: All patients underwent full neurologic and ophthalmologic examinations. The neurologic examinations included assessments of initial symptoms, intelligence quotient tests, psychologic tests, and either magnetic resonance imaging or computed tomography. The ophthalmologic examinations included visual acuity on an Early Treatment Diabetic Retinopathy Study chart, intraocular pressure color vision assessment, slit-lamp and fundus examination, Goldmann perimetry, fundus autofluorescence, optical coherence tomography and fluorescein angiography, electro-oculography, electroretinography, and flash visual evoked potentials. Direct sequencing of the SPG11 and SPG15 genes and gene-dosage analysis for the former were performed for 4 of these index patients. MAIN OUTCOME MEASURES: Identification of new mutations in the SPG11 gene, validating its implication in Kjellin's syndrome. RESULTS: The first signs appear before the age of 10 years, with late verbal development and difficulty running and walking. Life expectancy is between 30 and 40 years. The secondary ophthalmologic symptoms only moderately affect visual acuity. In addition to the classic symptoms, 3 of the 7 patients displayed small whitish lens opacities, and 3 neurologically unaffected parents (father or mother), all heterozygous carriers, exhibited whitish retinal dots. All the patients who were tested carried SPG11, not SPG15, mutations. CONCLUSIONS: Neurologic signs of SPG11 mutations emerge in early infancy, with walking and language difficulties. Onset of paraplegia occurs at the end of the first decade or during the second decade. Retinal changes, an integral part of SPG11 mutations in this series of patients, are only observed once the paraplegia has become apparent. PMID- 21035868 TI - Prevalence and predictors of ocular complications associated with cataract surgery in United States veterans. AB - PURPOSE: To investigate the prevalence and predictors of intraoperative and 90 day postoperative ocular complications associated with cataract surgery performed in the United States Veterans Health Administration (VHA) system. DESIGN: Retrospective cohort study. PARTICIPANTS: Forty-five thousand eighty-two veterans who underwent cataract surgery in the VHA. METHODS: The National Patient Care Database was used to identify all VHA patients who underwent outpatient extracapsular cataract surgery and who underwent only 1 cataract surgery within 90 days of the index surgery between October 1, 2005, and September 30, 2007. Data collected include demographics, preoperative systemic and ocular comorbidities, intraoperative complications, and 90-day postoperative complications. Adjusted odds ratios (ORs) of factors predictive of complications were calculated using logistic regression modeling. MAIN OUTCOME MEASURES: Intraoperative and postoperative ocular complications within 90 days of cataract surgery. RESULTS: During the study period, 53786 veterans underwent cataract surgery; 45082 met inclusion criteria. Common preoperative systemic and ocular comorbidities included diabetes mellitus (40.6%), chronic pulmonary disease (21.2%), age-related macular degeneration (14.4%), and diabetes with ophthalmic manifestations (14.0%). The most common ocular complications were posterior capsular tear, anterior vitrectomy, or both during surgery (3.5%) and posterior capsular opacification after surgery (4.2%). Predictors of complications included: black race (OR, 1.38; 95% confidence interval [CI], 1.28-1.50), divorced status (OR, 1.10; 95% CI, 1.03-1.18), never married (OR, 1.26; 95% CI, 1.14-1.38), diabetes with ophthalmic manifestations (OR, 1.33; 95% CI, 1.23 1.43), traumatic cataract (OR, 1.80; 95% CI, 1.40-2.31), previous ocular surgery (OR, 1.29; 95% CI, 1.02-1.63), and older age. CONCLUSIONS: In a cohort of United States veterans with a high preoperative disease burden, selected demographic factors and ocular comorbidities were associated with greater risks of cataract surgery complications. Further large-scale studies are warranted to investigate cataract surgery outcomes for non-VHA United States patient populations. PMID- 21035869 TI - A randomized controlled trial of alleviated positioning after small macular hole surgery. AB - OBJECTIVE: To establish whether the success rate of surgery for small idiopathic macular holes (diameter, <= 400 MUm) is significantly reduced if facedown positioning is replaced by simply taking care to avoid the supine position. DESIGN: Randomized, controlled, parallel-assignment, open-label, interventional, multicenter clinical trial. PARTICIPANTS: Sixty-nine patients from 6 specialized vitreoretinal units, randomized into 2 parallel groups and followed up after surgery for 3 months. METHODS: All patients underwent pars plana vitrectomy, peeling of any epiretinal membrane, and 17% C2F6 gas filling. Patients then were advised randomly to observe either strict facedown positioning for 22 of 24 hours or simply to avoid the supine position for 10 days. MAIN OUTCOME MEASURES: The primary outcome measure was the rate of anatomic closure 3 months after surgery. Main secondary measurements included Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity, progression of cataract, and frequency of complications. RESULTS: The mean size of macular holes was approximately 300 MUm in both groups. Closure rates were more than 90% in both groups: 32 (91.4%) of 34 eyes in the alleviated positioning group versus 32 (94.1%) of 35 eyes in the facedown positioning group (lower margin of 95% confidence interval of difference, 14.88%). The ETDRS scores at 3 months increased in both groups by 10.23 +/- 14.64 and 10.52 +/- 14.54 letters, respectively. Progression of cataract and the rate of other complications were not significantly different in the 2 groups. CONCLUSIONS: The success rate of surgery for idiopathic macular holes of 400 MUm or smaller is not significantly reduced if facedown positioning is replaced by simply taking care to avoid the supine position. These macular holes can be treated by streamlined surgery, that is, with no internal limiting membrane peeling and no facedown positioning (only avoidance of the supine position) with a closure rate of more than 90% and a mean gain in visual acuity of more than 2 ETDRS lines at 3 months. PMID- 21035870 TI - The heritability and sibling risk of angle closure in Asians. AB - PURPOSE: To describe the heritability and sibling risk for angle closure. DESIGN: Prospective clinical study. PARTICIPANTS: Probands with primary angle closure (PAC) and primary angle-closure glaucoma (PACG) and their first-degree relatives. METHODS: One hundred probands with PAC and PACG and their first-degree relatives were examined prospectively. All subjects underwent an ophthalmic evaluation that included slit-lamp examination, optic disc evaluation, and gonioscopy. An angle was classified as narrow if the posterior (usually pigmented) trabecular meshwork could be seen for less than 180 degrees of the angle circumference. The heritability of narrow angles was calculated by threshold models. The sibling recurrence and relative risk of having narrow angles compared with the general population was calculated using estimation of sibling genetic risk parameters, corrected for single ascertainment bias. MAIN OUTCOME MEASURES: Heritability and sibling risk for narrow angles. RESULTS: One hundred probands (consisting of 76 subjects with PACG and 24 with PAC) were examined together with 327 first-degree relatives. There were 76 female probands and 24 male probands. Of the first degree relatives, 146 were male and 181 were female. Of the 327 first-degree relatives, 105 (32.1%) had narrow angles. The heritability of narrow angles was 58.8% overall, with the genetic variance being 2.30 and the phenotypic variance being 3.91. Of the 515 sibling pairs examined, 171 (33.1%) pairs had both siblings unaffected, 113 (21.9%) pairs had both siblings affected, 231 (45.0%) pairs had 1 sibling affected. The sibling recurrence risk for having narrow angles was 49% (95% confidence interval, 41.6%-56.8%), whereas the sibling relative risk for narrow angles was 7.57 (95% confidence interval, 6.41-8.74). CONCLUSIONS: A high heritability of narrow angles of almost 60% was found. Siblings of Chinese patients with PAC or PACG have almost a 50% probability of having narrow angles and are more than 7 times more likely to have narrow angles than the general population. PMID- 21035871 TI - Axial length measurements by contact and immersion techniques in pediatric eyes with cataract. AB - PURPOSE: To compare axial length measurements by contact and immersion techniques in pediatric cataractous eyes. DESIGN: Prospective, comparative case series. PARTICIPANTS: In this prospective study, 50 cataractous eyes of 50 children were enrolled. In bilateral cataract, only 1 eye was selected to avoid a correlation effect in statistical analyses. METHODS: Axial length was measured by both contact and immersion techniques for all eyes, randomized as to which to perform first to avoid measurement bias. MAIN OUTCOME MEASURES: Axial length measured by contact and immersion techniques and the difference between contact and immersion technique axial length measurements. RESULTS: Mean age+/-standard deviation at cataract surgery and at axial length measurement was 3.87+/-3.72 years. Axial length measurement by contact technique was significantly shorter as compared with immersion technique (21.36+/-3.04 mm and 21.63+/-3.09 mm, respectively; P<0.001). Axial length measurements using the contact technique were on an average 0.27 mm shorter than those obtained using the immersion technique. Forty two eyes (84%) had shorter axial length when measured using the contact technique as compared with the immersion technique. Lens thickness measurement by contact technique was not significantly different from that of immersion technique (3.61+/-0.74 and 3.60+/-0.67 mm, respectively; P = 0.673). Anterior chamber depth measurement was significantly more shallow with the contact technique (3.39+/ 0.59 mm and 3.69+/-0.54 mm, respectively; P<0.001). Intraocular lens power needed for emmetropia was significantly different (28.68 diopters [D] vs. 27.63 D; P<0.001). CONCLUSIONS: Contact A-scan measurements yielded shorter axial length than immersion A-scan measurements. This difference was mainly the result of the anterior chamber depth rather than the lens thickness value. During intraocular lens (IOL) power calculation, if axial length measured by contact technique is used, it will result in the use of an average 1-D stronger IOL power than is actually required. This can lead to induced myopia in the postoperative refraction. PMID- 21035873 TI - Depressive symptoms during pregnancy: impact on neuroendocrine and neonatal outcomes. AB - OBJECTIVE: To explore the interplay of maternal depressive symptoms on the infant limbic-hypothalamic-pituitary axis (LHPA) and neurological development. DESIGN: Pregnant women were monitored for depressive symptoms using the Beck Depression Inventory (BDI) at 28, 32, and 37 weeks of gestation and at delivery. A mixture growth curve analysis divided the women into three risk groups: low/stable, intermediate, and high/increasing depression based on BDI scores. The infant neuroendocrine system was examined using cord blood for adrenocorticotrophic hormone (ACTH) and cortisol measurements. Two-week-old infants were examined using Neonatal Intensive Care Unit Neurobehavioral Scale (NNNS). RESULTS: Infants born to women of the high/increasing depression group had significant ACTH elevation at birth. On NNNS examination, these infants were more hypotonic and habituated to auditory and visual stimuli. CONCLUSION: When compared to non depressed women, maternal depressive symptoms, even in the absence of major depressive disorder, appeared to facilitate a different developmental pathway for the infant LHPA and early neurological development. PMID- 21035874 TI - Complementary anti-inflammatory actions of the beta2-adrenoceptor agonist clenbuterol and the glucocorticoid dexamethasone in rat brain. AB - Systemic administration of the beta(2)-adrenoceptor agonist clenbuterol induces expression of IL-1beta and its negative regulators, interleukin-1 receptor antagonist (IL-1ra) and the interleukin-1 type II decoy receptor (IL-1RII) in rat brain. Clenbuterol also increases central expression of the broad spectrum anti inflammatory cytokine interleukin-10 (IL-10) and its downstream signalling molecule, suppressor of cytokine signalling-3 (SOCS-3). Here we examine the impact of combined treatment with clenbuterol (0.5mg/kg) and the glucocorticoid dexamethasone (1mg/kg) on mRNA expression of IL-1beta and the IL-1beta-inducible gene iNOS, on IkappaBalpha mRNA expression and NFkappaB activation, and on mRNA expression of the anti-inflammatory molecules IL-1ra, IL-1RII, IL-10 and SOCS-3 in rat cortex, striatum and hippocampus. Dexamethasone inhibited induction of IL 1beta and iNOS mRNA expression by clenbuterol in all three brain regions, without altering its ability to induce IL-1ra mRNA expression. In the case of IL-1RII, dexamethasone further augmented clenbuterol-induced IL-1RII mRNA expression in hippocampus and striatum. These data highlight a mechanistic dissociation between the ability of beta(2)-adrenoceptor activation to induce expression of IL-1beta, and its negative regulators IL-1ra and IL-1RII in the brain. Treatment with either dexamethasone or clenbuterol alone independently induced IkappaBalpha mRNA expression, and elicited a concomitant decrease in the DNA binding of NFkappaB in all three brain regions. In the hippocampus and striatum dexamethasone treatment did not influence the ability of clenbuterol to induce IL-10 mRNA expression. In contrast in the cortex, induction of IL-10 and SOCS-3 mRNA expression by clenbuterol administered in combination with dexamethasone was less than induced by clenbuterol alone. Overall these data indicate that combined treatment with dexamethasone and the beta(2)-adrenoceptor agonist clenbuterol elicit complementary anti-inflammatory actions in the CNS. Specifically, dexamethasone inhibits expression of pro-inflammatory cytokines, whereas clenbuterol has the added benefit of promoting expression of anti-inflammatory molecules including IL 1ra, IL-1RII, IL-10 and SOCS-3. PMID- 21035872 TI - Severity of diabetic retinopathy and health-related quality of life: the Los Angeles Latino Eye Study. AB - OBJECTIVE: To assess the impact of diabetic retinopathy (DR) and its severity on health-related quality of life (HRQOL) in a population-based sample of Latinos with type 2 diabetes mellitus (DM). DESIGN: Cross-sectional population-based study, the Los Angeles Latino Eye Study (LALES). PARTICIPANTS: We included 1064 LALES participants with DM. METHODS: We measured HRQOL by the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) and the Medical Outcomes Study 12-item Short Form Health Survey (SF-12). We assessed DR by masked standardized grading of stereoscopic photographs from 7 standard fields. Severity of DR in eyes was graded using a modified Airlie House classification. The severity scores from each eye were then concatenated to create a single per person grade ranging from 1 (no DR in either eye) to 15 (bilateral PDR). Multiple linear regression analyses were performed to determine the independent relationship between severity of DR and HRQOL after adjusting for covariates. MAIN OUTCOME MEASURES: Scores on the NEI-VFQ-25 and SF-12. RESULTS: More severe DR was associated with worse HRQOL scores on all of the NEI-VFQ-25 and SF-12 subscales (P<0.05). Individuals with DR from grade 2 (minimum nonproliferative diabetic retinopathy [NPDR]) through grade 8 (unilateral moderate NPDR) show a modest decline in HRQOL. However, the decline becomes significantly steeper between steps 8 (unilateral moderate NPDR) and 9-15 (bilateral moderate NPDR to bilateral PDR). The domains with the most significant impact were for vision related daily activities, dependency, and mental health. CONCLUSIONS: Greater severity of DR was associated with lower general and vision-specific HRQOL. Persons with bilateral moderate NPDR had the most substantial decrease in quality of life compared with those with less severe DR. The prevention of incident DR and, more important, its progression from unilateral to bilateral NPDR is likely to have a positive impact on a person's HRQOL and should be considered an important goal in management of individuals with DM. PMID- 21035875 TI - Diagnostic accuracy of the nasal obstruction index in detecting adenoid hypertrophy in children without allergy. AB - OBJECTIVE: We have previously compared the capacity of the nasal obstruction index (NOI) and nasal fiberoptic endoscopy (NFE) to detect adenoid hypertrophy (AH) in children and found no agreement between them. However, the prevalence of false positive results was significantly higher in children with allergic rhinitis (AR), thus suggesting that AR may be a possible causative factor. The aim of this study was to verify the diagnostic accuracy of the NOI in detecting AH by comparing NOI scores with NFE findings in a selected series of non-allergic children affected by nasal obstruction. METHODS: This prospective study was carried out at the Outpatient Clinics of the Departments of Specialist Surgical Sciences and Maternal and Pediatric Sciences of the University of Milan, Italy, and involved 154 non-allergic children aged 3-12 years in whom otological diseases and/or perceived nasal obstruction led to the suspicion of adenoid obstruction. The diagnostic accuracy of NOI was tested at all of the thresholds obtained by combining all of the cut-off points of NFE and NOI. RESULTS: Sixty two percent of the children had otological diseases. The choanal opening was completely blocked by the adenoids in 40% of the children, whereas NOI indicated severe clinical obstruction in only 16%. The analysis of diagnostic accuracy showed that sensitivity and specificity were respectively 17-96% and 15-91% depending on the threshold, with no simultaneously acceptable sensitivity and specificity values at any threshold and AUC values of <=0.7 at all thresholds. CONCLUSIONS: In comparison with NFE, the NOI seems to be inaccurate in detecting AH in non-allergic children with nasal obstruction. PMID- 21035876 TI - Mandibular fractures in children: analysis of 61 cases and review of the literature. AB - OBJECTIVE: The purpose was to evaluate the incidence, etiology, site and patterns, management and treatment methods, and outcome of pediatric patients with mandibular fractures. METHODS: Pediatric patients (1.5-16 years old) with mandibular fractures, treated at the Soroka University Medical Center were included in the study. Age, gender, etiology, site and type of fracture, associated injuries, mode of treatment, outcome, complications, and follow up were evaluated. The cases were divided into 3 age groups: Group A: 1.5-5 years, Group B: 6-11 years, and Group C: 12-16 years. RESULTS: Sixty one patients were included in the study. The male to female ratio was 2:1. Motor vehicle accident was the most common cause. Associated trauma was more common in young children. The condyle was involved in 54% of the fractures. Closed reduction and intermaxillary fixation was the most common treatment used. Complications were rare. CONCLUSION: Management of mandibular fracture in the pediatric age group is a challenge. The anatomical complexity of the developing mandible and teeth strongly suggest the use of surgical techniques that are different from those routinely used in adults. The conservative approach is recommended. Whenever possible closed reduction should be the treatment of choice. PMID- 21035877 TI - Study of auditory function in children with chronic lung diseases. AB - OBJECTIVE: Chronic hypoxia has an evident effect on cochlear function and hearing sensitivity. Otoacoustic emissions' testing is efficient in detecting subtle cochlear dysfunction. This cross sectional study was designed to assess the cochlear function in children with chronic lung diseases who were exposed to prolonged hypoxia and prolonged use of ototoxic drugs (as aminoglycosides) using basic audiological evaluation and transient evoked otoacoustic emissions testing. METHODS: The study was carried out on 30 Egyptian children with chronic lung disease recruited from the Pediatric Chest Clinic, Children's hospital, Ain Shams University. Twenty normal children were included as control. RESULTS: Six patients (20%) showed abnormal otoacoustic emissions. A significant effect of hypoxia on otoacoustic emissions findings was found (P<0.05). However, there was no significant effect of inhaled aminoglycosides on auditory functions whether pure tone audiometry, speech audiometry and transient evoked otoacoustic emissions testing. CONCLUSIONS: Children with chronic lung diseases are liable to cochlear dysfunction due to prolonged hypoxia. Inhaled aminoglycosides in chronic lung diseases is relatively safe on auditory functions. PMID- 21035879 TI - Measuring health related quality of life in coronary heart disease: the importance of feeling well. AB - Health related quality of life (HRQoL) is used increasingly as a measure of the outcome of CHD. As an improvement in survival of CHD continues, assessment of HRQoL has become an important and useful outcome measure complementing the traditional "hard outcomes" such as mortality for evaluating benefits of medical interventions. Increasing number of clinical trials is applying HRQoL as an outcome measure of CHD therapy. Assessment of HRQoL in CHD should comprise a disease-specific measure in addition to a generic measure. This review aims to provide an overview of generic, disease-specific, and utility measures used in the assessment of HRQoL in CHD. PMID- 21035880 TI - Morphological and dynamic features of normal mitral valve evaluated by dual source computed tomography. PMID- 21035878 TI - Neuroprotection for traumatic brain injury: translational challenges and emerging therapeutic strategies. AB - Traumatic brain injury (TBI) causes secondary biochemical changes that contribute to subsequent tissue damage and associated neuronal cell death. Neuroprotective treatments that limit secondary tissue loss and/or improve behavioral outcome have been well established in multiple animal models of TBI. However, translation of such neuroprotective strategies to human injury have been disappointing, with the failure of more than thirty controlled clinical trials. Both conceptual issues and methodological differences between preclinical and clinical injury have undoubtedly contributed to these translational difficulties. More recently, changes in experimental approach, as well as altered clinical trial methodologies, have raised cautious optimism regarding the outcomes of future clinical trials. Here we critically review developing experimental neuroprotective strategies that show promise, and we propose criteria for improving the probability of successful clinical translation. PMID- 21035881 TI - Arrhythmogenic right ventricular cardiomyopathy: magnetic resonance imaging does not detect early stages of the disease. PMID- 21035883 TI - Sources of Salmonella contamination during broiler production in Eastern Spain. AB - Prevention of Salmonella contamination of poultry products requires detailed knowledge of the main sources associated with its presence in the production system. The aims of this study were to determine the main sources of Salmonella contamination in broiler production during growing, to assess the risk factors for Salmonella contamination at the end of the rearing period and to determine the main serovars involved in broiler production systems in Eastern Spain. A total of 65 different broiler houses from different farms were sampled. Each house was sampled at different times during the rearing period. First, when the previous flock was taken to the slaughterhouse, samples of dust, surfaces and previous flock faeces were collected. After cleaning and disinfection (C&D), samples of dust and surfaces were also taken. On the first day of rearing, samples of water, bedding, farming boots, meconiums, delivery-box liners and feed were collected. During rearing, feed samples were taken directly from the truck and from feeders. On slaughter day, samples of dust, surfaces, water, feed and faeces were also collected. Finally, two days after slaughter, carriers (rodents, flies and beetles) were trapped. All samples collected were analysed according to ISO 6579:2002 (Annex D) and positive samples were serotyped in accordance with Kauffman-White-Le-Minor technique. Our results showed that all different types of samples collected were contaminated with Salmonella (prevalence ranged between 1.5% and 38.6%). The most contaminated samples related with poultry production were: delivery-box liners (32.0%), faeces samples (31.2%), dust samples (25.0%), farming boots (19.7%) and feed from feeders (16.0%). However, the most important risk factors for Salmonella contamination of the flocks at the end of the rearing period were Salmonella status of the house after cleaning and disinfection, Salmonella status of day-old chick flocks and feed from feeders. Twenty-one different serovars were isolated from the samples analysed. The most prevalent were in decreasing order: Salmonella Enteritidis (52.9%), S. Hadar (17.8%), S. Virchow (8.9%) and S. Ohio (5.4%). The study suggested that there are many sources for Salmonella contamination and persistence in broiler production. Hence, the whole production chain needs to be controlled to eradicate the bacteria from primary production. PMID- 21035882 TI - Simvastatin administration reduces thromboxane production in subjects taking aspirin: links between aspirin resistance and thrombin generation. AB - BACKGROUND: Growing evidence indicates that statins may reduce thromboxane A(2) synthesis and thrombin generation. We investigated the relationships between thromboxane production, thrombin generation, and oxidative stress in patients receiving aspirin before and after statin administration. METHODS: An open-label study was conducted in 112 men, aged 54.4 +/- 7.3 years, at an increased cardiovascular risk receiving aspirin (75 mg/d). Prior to and following a 3-month simvastatin treatment (40 mg/d), we evaluated circulating thromboxane B(2) (TXB(2)), inflammatory markers, 8-isoprostane, and prothrombin fragment 1.2 (F1.2), a marker of thrombin generation, which was also measured in blood collected every 60s at the site of standardized skin incisions. RESULTS: Subjects (n=28) with pretreatment TXB(2) concentrations in the highest quartile ("aspirin resistant patients") were more frequently current smokers and had elevated C reactive protein (CRP), interleukin-6, 8-isoprostane, shorter bleeding time, and increased F1.2 production in a model of microvascular injury, when compared with the 3 remaining quartiles (all, p<0.001). Simvastatin decreased serum TXB(2) in the whole group (by 20%, p=0.0008). Patients in the highest quartile of the baseline TXB(2) had still higher posttreatment TXB(2), CRP, interleukin-6, and F1.2 formation following injury (all, p<0.001). Simvastatin-induced change in TXB(2) correlated with the magnitude of changes in maximum levels and the velocity of F1.2 formation (all p<0.001) but not with changes in inflammatory markers or lipid profile. CONCLUSIONS: The study shows that statins significantly reduce platelet TXA(2) formation in patients taking low-dose aspirin and this effect is associated with attenuated thrombin formation in response to vascular injury. PMID- 21035884 TI - Occurrence of foodborne pathogens and characterization of Staphylococcus aureus in cheese produced on farm-dairies. AB - The objective of this study was to address knowledge gaps identified in an earlier risk assessment of Staphylococcus aureus and raw milk cheese. A survey of fresh and short-time ripened cheeses produced on farm-dairies in Sweden was conducted to investigate the occurrence and levels of S. aureus, Listeria monocytogenes and Escherichia coli, to characterize S. aureus isolates with special emphasis on enterotoxin genes, antibiotic resistance, bio-typing and genetic variation, and to collect information related to production practices. In general, the hygienic quality of farm-dairy cheeses appeared to be of an acceptable microbiological quality, e.g. L. monocytogenes and staphylococcal enterotoxin were not detected in cheese samples. However, E. coli and enterotoxigenic S. aureus were frequently found in raw milk cheeses and sometimes at levels that are of concern, especially in fresh cheese. Interestingly, levels in raw milk fresh cheese were significantly lower when starter cultures were used. Up to five S. aureus colonies per cheese, if possible, were characterized and about 70% of isolates carried one or more enterotoxin genes, most common were sec and sea. The Ovine biotype (73%) was most common among isolates from goat milk cheese and the Human biotype (60%) from cow milk cheese. Of all isolates, 39% showed decreased susceptibility to penicillin, but the proportion of isolates from cows' cheese (66%) compared to isolates from goats' cheese (27%) was significantly higher. S. aureus isolates with different properties were detected in cheese from the same farm and, sometimes even the same cheese. Isolates with the same pulsed-field gel electrophoresis (PFGE)-pattern were detected on geographically distant dairies. This indicates that multiple sources and routes of contamination are important. To improve the safety of these products efforts to raise awareness of the importance of hygiene barriers and raw milk quality as well as improved process control can be suggested, e.g. use of starter cultures and monitoring of fermentation with a pH-meter. For future safety assessments, a better understanding of factors determining toxin production in these cheeses is needed. PMID- 21035885 TI - Severe leucopenia associated with Sitagliptin use. AB - We report the case of a type 2 diabetes subject who developed severe leucopenia associated with treatment with the dipeptidil-peptidase 4 enzyme inhibitor Sitagliptin and highlights DPP4 inhibitors as a possible cause of unexplained hematolgical abnormalities in patients receiving DPP4-inhibitor treatment. PMID- 21035886 TI - The effects of fasting plasma glucose variability and time-dependent glycemic control on the long-term risk of retinopathy in type 2 diabetic patients. AB - Long-term fasting plasma glucose (FPG) variability was a risk factor for proliferative diabetic retinopathy (PDR) independent of the mean FPG or HbA1c in people with type 2 diabetes. PDR development was also significantly associated with mean HbA1c more than 5 years earlier and with mean FPG more than 10 years earlier. PMID- 21035887 TI - Chronic interdigital dermatophytic infection: a common lesion associated with potentially severe consequences. AB - Interdigital intertrigo and onychomycosis has the potential cause of severe bacterial infectious complications with pain, mobility problems, abscess, erysipelas, cellulitis, fasciitis and osteomyelitis. In another hand, diabetic neuropathy, which affects 60-70% of those with diabetes mellitus, is one of the most troubling complications for persons with diabetes. These people are high suspecting to be infected by dermatophytic infections in interdigital spaces or onychomycosis witch are frequently induce damage to the stratum corneum, leading to bacterial proliferation and secondary infection. A patient presented with an asymptomatic warm, painless, erythematous swelling of the second left toe, which had been present for a few weeks. Clinically, the lesion was categorized as erysipelas upon an insidious abscess formation. Further investigation was undertaken to confirm the presence of diabetes. Leg erysipelas is a common affection which, according to various studies, has both local concomitants (interdigital intertrigo, lymphoedema, surgical antecedents) and/or general causes (immune suppression, diabetes, alcoholism, etc). Interdigital intertrigo, tinea pedis, and onychomycosis present as public health problems that could trigger serious deterioration in patient quality of life, due to complications induced by secondary bacterial infections. PMID- 21035888 TI - Could clinical inertia in part explain the unexpected association of insulin therapy with poorer cardiovascular outcomes in observational studies on diabetes? PMID- 21035889 TI - Increased epicardial adipose tissue in type 1 diabetes is associated with central obesity and metabolic syndrome. AB - AIMS: The present study evaluated the relationship between metabolic syndrome (MS), body fat composition and epicardial adipose tissue (EAT) in type 1 diabetes. Epicardial adipose tissue is a new independent marker of coronary artery disease (CAD). METHODS: forty-five type 1 diabetic women were evaluated (age 36 +/- 9 years; body mass index 24.6 +/- 4.4 kg/m(2)). Metabolic syndrome was defined by the World Health Organization criteria. Body fat composition and EAT were analyzed by dual-energy-X-ray absorptiometry and echocardiogram, respectively. RESULTS: twenty patients (45%) had MS. Patients with MS had greater android (central) fat deposition than patients without MS (41.9 +/- 2.0% vs. 33.7 +/- 1.8%, p=0.004). Total body fat and gynoid (peripheric) fat distribution were similar between the groups. Mean EAT was higher in patients with MS (6.15 +/- 0.34 mm vs. 4.96 +/- 0.25 mm; p=0.006) and EAT was positively correlated with android (central) fat distribution (r=0.44; p=0.002), however no correlation was found with gynoid (peripheric) fat distribution. CONCLUSIONS: there was a high incidence of MS in type 1 diabetes related to increased central adiposity, despite the absence of obesity. Metabolic syndrome and central obesity were associated with increased EAT. Thus, young non-obese type 1 diabetic women with central adiposity and/or MS may have increased EAT, what may predict CAD risk. PMID- 21035890 TI - Trends in deliveries in women with gestational diabetes in Spain, 2001-2008. AB - We examined trends and characteristics of deliveries in women with gestational diabetes in Spain from 2001 to 2008. There were 101,643 deliveries with gestational diabetes among 2,782,369 delivery discharges (3.6%) with no increase over time. Rate of caesarean section increased (19-24.2%) and length of stay decreased. PMID- 21035891 TI - Association between type 1 diabetes mellitus and remitting seronegative symmetrical synovitis with pitting edema: a case report. AB - A 59-year-old female with type 1 diabetes and RS3PE had HLA types known to be associated with both diseases. Type 1 diabetes patients suffering from polyarthritis and pitting edema should be examined for possible RS3PE and glucocorticoid therapy may be indicated despite the diabetes. PMID- 21035892 TI - Conservation paleobiology: putting the dead to work. AB - Geohistorical data and analyses are playing an increasingly important role in conservation biology practice and policy. In this review, we discuss examples of how the near-time and deep-time fossil record can be used to understand the ecological and evolutionary responses of species to changes in their environment. We show that beyond providing crucial baseline data, the conservation paleobiology perspective helps us to identify which species will be most vulnerable and what kinds of responses will be most common. We stress that inclusion of geohistorical data in our decision-making process provides a more scientifically robust basis for conservation policies than those dependent on short-term observations alone. PMID- 21035893 TI - Light pollution as a biodiversity threat. PMID- 21035894 TI - Serum concentration and interaction properties of MBL/ficolin associated protein 1. AB - Recently, a novel protein named MBL/ficolin associated protein-1 (MAP-1) derived from the MASP1 gene through differential splicing was identified. In the present study, we established biochemical characteristics, determined the serum level and assessed the interactions between the lectin complement pathway (LCP) recognition molecules and MAP-1. We expressed recombinant MAP-1 in CHO DG44 cells, developed a quantitative ELISA assay based on a MAP-1 specific monoclonal capture antibody and measured the serum levels in 100 Danish blood donors. In addition we assessed the association properties between MAP-1 and Ficolin-2, -3 and MBL in serum using ELISA and density gradient ultra centrifugation. When recombinant MAP-1 was subjected to N-glycosidase F treatment the molecular mass decreased from ~45 kDa to ~40 kDa equivalent with the calculated molecular mass from the deduced amino acid sequence without the signal peptide. We found that serum MAP-1 was very stable when subjected to repeated freeze and thaw cycles. The mean serum concentration of MAP-1 was found to be 240 ng/ml (range: 115-466 ng/ml). MAP-1 was predominantly found in complex with Ficolin-3 and to a lesser degree with Ficolin-2 and MBL and by use of density gradient ultra centrifugation we could show that the major part of serum MAP-1 circulates in complex with the LCP molecules. In conclusion, these results show that MAP-1 is a highly stable glycosylated human serum protein found in complex with Ficolin-3, Ficolin-2 and MBL. PMID- 21035895 TI - Differential localization and processing of apoptotic proteins in Malpighian tubules of Drosophila during metamorphosis. AB - Drosophila development proceeds through three larval stages, before it pupates to reach adulthood. During pupation, larval tissues are destructed by programmed cell death and replaced by adult structures. Programmed cell death is a tightly regulated process accomplished by the induction of three closely linked pro apoptotic genes reaper, hid and grim, ultimately leading to the activation of caspases, DRONC and DRICE and results in cell death. Unlike other larval tissues, Malpighian tubules are unique in not undergoing characteristic ecdysone-induced apoptosis and are carried to the adults. In this paper we show that apoptotic proteins, HID, GRIM, DRONC and DRICE are expressed in the Malpighian tubules, however they are sequestered in the nucleus. Significantly DRONC and DRICE are not enzymatically processed to active forms in the Malpighian tubules, however, ectopic expression of pro-apoptotic proteins leads to malformed Malpighian tubules and lethality. We also show that the Drosophila inhibitor of apoptotic protein 1, DIAP1, is localized and processed differently in Malpighian tubules. These results provide first evidence in favor of differential activity of apoptotic proteins in Malpighian tubules. PMID- 21035896 TI - Molecular mechanisms of ultraviolet radiation-induced immunosuppression. AB - Solar ultraviolet radiation (UVR) is well known for its immunosuppressive properties. UVR can suppress immune reactions both in a local and a systemic fashion. One of the major molecular mediators of photoimmunosuppression is UVR induced DNA damage. In contrast to immunosuppressive drugs, UVR does not act in a general but antigen-specific fashion. This is due to the induction of regulatory T cells. Epidermal Langerhans cells harboring UVR-induced DNA damage appear to be essentially involved in the induction of these cells. Cytokines including interleukin (IL)-12, -18 and -23 exert the capacity to reduce UVR-induced DNA damage via induction of DNA repair. Accordingly, these cytokines prevent UVR mediated immunosuppression. In contrast to IL-18, IL-12 and IL-23 can also inhibit the suppressive activity of regulatory T cells by a mechanism which still needs to be determined. Clarification of the molecular mechanisms underlying UVR induced immunosuppression will help to develop new immunosuppressive therapeutic strategies by utilizing UVR-induced regulatory T cells for the treatment of immune-mediated diseases. In addition, these insights will contribute to a better understanding of photocarcinogenesis since suppression of the immune system by UVR essentially contributes to the induction of skin cancer. PMID- 21035897 TI - The structure of the unliganded extracellular domain of the interleukin-6 signal transducer gp130 in solution. AB - Interleukin-6 (IL-6) plays an important role in immune responses and signals via two different pathways. When IL-6 binds to its non-signalling membrane-bound receptor (IL-6R), a non-covalent dimer of the ubiquitous interleukin-6 signal transducer gp130 is recruited to initiate intracellular signalling cascades. This so-called classical signalling pathway is restricted to cells expressing the membrane-bound IL-6R, such as hepatocytes and certain leukocytes. In addition, an alternative trans-signalling pathway uses soluble forms of IL-6R (sIL-6R) in complex with IL-6 to activate cells expressing gp130, but not membrane-bound IL 6R. In both cases, a tetrameric or hexameric signalling complex consisting of two gp130 molecules and one or two molecules each of IL-6 and (s)IL-6R is formed. The structure of the hexameric complex of the ligand-binding domains of gp130 (D1-D3) with IL-6 and sIL-6R has been solved by X-ray crystallography as well as the full length extracellular part of gp130 (D1-D6) as a monomer. Since gp130 exists as a preformed dimer on the cell surface, we used a sgp130Fc fusion protein - consisting of two extracellular gp130 regions (D1-D6) dimerised by an IgG1-Fc part - to study the structure of unliganded gp130 extracellular domains in solution by small-angle X-ray scattering (SAXS). The SAXS data indicated that sgp130Fc forms a rigid molecule in solution. The low resolution structural model reveals an elongated assembly with an Fc base and two gp130 arms, whereby the orientation of the ligand-binding domains D1-D3 with respect to the membrane proximal domains D4-D6 differs from that in the crystallographic monomer. Functional implications of these findings are discussed. PMID- 21035898 TI - Group 1 and 2 LEA protein expression correlates with a decrease in water stress induced protein aggregation in horsegram during germination and seedling growth. AB - Plants produce an array of proteins as a part of a global response to protect the cell metabolism when they grow under environmental conditions such as drought and salinity that generate reduced water potential. The synthesis of hydrophilic proteins is a major part of the response to water deficit conditions. An increased expression of LEA proteins is thought to be one of the primary lines of defense to prevent the loss of intercellular water during adverse conditions. These LEA proteins are known to prevent aggregation of a wide range of other proteins. In this study we report the water stress induced protein aggregation and its abrogation followed by expression of group 1 and group 2 LEA proteins of water soluble proteomes in horsegram. Water stress caused an increased protein aggregation with magnitude and duration of stress in horsegram seedlings. Tissue specific expression of LEA 1 protein decreased in the embryonic axis when compared to cotyledons in 24h stressed seedlings. We found no cross reaction of LEA 1 with proteome of 48h stressed embryonic axis and 72h stressed root and shoot samples. However, LEA 2 antibodies were cross reacted with four polypeptides with different molecular mass in shoot tissue samples and found no reaction with root proteome as evidenced from immuno-blot analysis. The role of LEA proteins in relation to protein aggregation during water stressed conditions was discussed. PMID- 21035899 TI - [Subconjunctival bevacizumab for corneal neovascularization]. AB - PURPOSE: To assess efficacy and safety of subconjunctival bevacizumab in corneal neovascularization treatment. METHODS: The study was a prospective case series that included patients treated with subconjunctival bevacizumab injections for corneal neovascularization over a period of four months. A dose of 2.5 mg (0.1 mL) of bevacizumab (25 mg/mL) was injected into the subconjunctival area 1-2mm behind the limbus near the corneal neovascularization. The main outcome measures were visual acuity, corneal neovascularization, as well as local and general side effects. RESULTS: Thirteen eyes of 12 patients were included. The mean patient age was 44.2 years (range, 18-87 years). Patients received from two to four bevacizumab injections. The mean corneal neovascularization area decreased from 41.1 to 33.7 % at day 45 (p=0.0003) and to 33.9 % at day 120 (p=0.0013). Median visual acuity changed from 1.32 to 1.28 LogMAR on day 45 and to 1.25 LogMAR on day 120. Subconjunctival bevacizumab was well tolerated without general side effects. There was no significant change in intraocular pressure. An epithelial defect was described in three patients after initiation of bevacizumab therapy. CONCLUSIONS: Subconjunctival bevacizumab injections were effective and safe in reducing corneal neovascularization within the first four months. Meanwhile, improving vision may provide additional strategies. PMID- 21035900 TI - Hospice care and the emergency department: rules, regulations, and referrals. AB - Emergency clinicians often care for patients with terminal illness who are receiving hospice care and many more patients who may be in need of such care. Hospice care has been shown to successfully address the multidimensional aspects of the end-of-life concerns of terminally ill patients: dying with dignity, dying without pain, reducing the burden on family and caregivers, and achieving a home death, when desired. Traditional emergency medicine training may fail to address hospice as a system of care. When they are unfamiliar with the hospice model, emergency clinicians, patients, and caregivers may find it difficult to properly use and interact with these care services. Potential poor outcomes include the propagation of misleading or inaccurate information about the hospice system and the failure to guide appropriate patient referrals. This article reviews the hospice care service model and benefits offered, who may qualify for hospice care, common emergency presentations in patients under hospice care, and a stepwise approach to initiating a hospice care referral in the emergency department. PMID- 21035901 TI - Evidence-based emergency medicine. Is therapeutic hypothermia for closed head trauma beneficial? PMID- 21035902 TI - Health literacy and emergency department outcomes: a systematic review. AB - STUDY OBJECTIVE: We assess emergency department (ED) patients' health literacy, the readability of ED patient materials, and the relationship between health literacy and ED outcomes through a systematic literature review. METHODS: PubMed, PsychInfo, CINAHL, Web of Knowledge, and ERIC were searched for studies published January 1, 1980, to July 15, 2010, conducted in the United States, reporting original data, and measuring ED patients' health literacy, the readability of ED materials, or the association between health literacy and ED-related outcomes. Two reviewers evaluated each study and abstracted information from included studies into evidence tables. RESULTS: We identified 413 articles, and 31 met inclusion criteria. Collectively, health literacy skills were assessed at or below the eighth-grade level for approximately 40% of ED patients. In contrast, ED patient materials were typically assessed at or above the ninth-grade level. Studies of adults aged 65 years and older found that those with lower health literacy were more likely to use the ED and incur higher ED costs. Studies of pediatric ED patients did not find direct effects of caregiver literacy on ED outcomes. CONCLUSION: A substantial proportion of ED patients have limited health literacy, and ED materials are typically too complex for these patients. It is important for EDs to evaluate the accessibility and patient understanding of information presented. The evidence linking health literacy to ED outcomes is limited. Additional research is needed to better understand the relationship between health literacy and ED outcomes. PMID- 21035903 TI - Emergency department crowding is associated with decreased quality of care for children with acute asthma. AB - STUDY OBJECTIVE: We seek to determine which dimensions of quality of care are most influenced by emergency department (ED) crowding for patients with acute asthma exacerbations. METHODS: This cross-sectional study with retrospective data collection included patients aged 2 to 21 years treated for acute asthma during November 2007 to October 2008 at a children's hospital ED. We studied 3 processes of care-asthma score, beta-agonist, and corticosteroid administration-and 9 quality measures representing 3 quality dimensions: timeliness (1-hour receipt of each process), effectiveness (receipt/nonreceipt of each process), and equity (language, identified primary care provider, and insurance). Primary independent variables were 2 crowding measures: ED occupancy and number waiting to see an attending-level physician. Models were adjusted for age, language, insurance, primary care access, triage level, ambulance arrival, oximetry, smoke exposure, and time of day. For timeliness and effectiveness quality measures, we calculated the adjusted risk of each quality measure at 5 percentiles of crowding for each crowding measure and assessed the significance of the adjusted relative interquartile risk ratios. For equity measures, we tested their role as moderators of the crowding-quality models. RESULTS: The asthma population included 927 patients. Timeliness and effectiveness quality measures showed an inverse, dose-related association with crowding, an effect not moderated by equity measures. Patients were 52% to 74% less likely to receive timely care and were 9% to 14% less likely to receive effective care when each crowding measure was at the 75th rather than at the 25th percentile (P<.05). CONCLUSION: ED crowding is associated with decreased timeliness and effectiveness-but not equity of care for children with acute asthma. PMID- 21035904 TI - Lean Thinking in emergency departments: a critical review. AB - Emergency departments (EDs) face problems with crowding, delays, cost containment, and patient safety. To address these and other problems, EDs increasingly implement an approach called Lean thinking. This study critically reviewed 18 articles describing the implementation of Lean in 15 EDs in the United States, Australia, and Canada. An analytic framework based on human factors engineering and occupational research generated 6 core questions about the effects of Lean on ED work structures and processes, patient care, and employees, as well as the factors on which Lean's success is contingent. The review revealed numerous ED process changes, often involving separate patient streams, accompanied by structural changes such as new technologies, communication systems, staffing changes, and the reorganization of physical space. Patient care usually improved after implementation of Lean, with many EDs reporting decreases in length of stay, waiting times, and proportion of patients leaving the ED without being seen. Few null or negative patient care effects were reported, and studies typically did not report patient quality or safety outcomes beyond patient satisfaction. The effects of Lean on employees were rarely discussed or measured systematically, but there were some indications of positive effects on employees and organizational culture. Success factors included employee involvement, management support, and preparedness for change. Despite some methodological, practical, and theoretic concerns, Lean appears to offer significant improvement opportunities. Many questions remain about Lean's effects on patient health and employees and how Lean can be best implemented in health care. PMID- 21035906 TI - "Sign right here and you're good to go": a content analysis of audiotaped emergency department discharge instructions. AB - STUDY OBJECTIVE: The goal of this study is to quantitatively and qualitatively assess the quality and content of verbal discharge instructions at 2 emergency departments (EDs). METHODS: This was a secondary data analysis of 844 ED audiotapes collected during a study of patient-emergency provider communication at 1 urban and 1 suburban ED. ED visits of nonemergency adult female patients were recorded with a digital audiotape. Of 844 recorded ED visits, 477 (57%) audiotapes captured audible discharge instructions suitable for analysis. Audiotapes were double coded for the following discharge content: (1) explanation of illness, (2) expected course, (3) self-care, (4) medication instructions, (5) symptoms prompting return to the ED, (6) time-specified for follow-up visit, (7) follow-up care instructions, (8) opportunities for questions, and (9) patient confirmation of understanding. Analysis included descriptive statistics, chi(2) tests, 2-sample t tests, and logistic regression models. RESULTS: Four hundred seventy-seven of 871 (55%) patient tapes contained audible discharge instructions. The majority of discharges were conducted by the primary provider (emergency physician or nurse practitioner). Ninety-one percent of discharges included some opportunity to ask questions, although most of these were minimal. Only 22% of providers confirmed patients' understanding of instructions. CONCLUSION: Verbal ED discharge instructions are often incomplete, and most patients are given only minimal opportunities to ask questions or confirm understanding. PMID- 21035907 TI - Solitary nasal mass: an unusual diagnosis. PMID- 21035905 TI - Factors associated with cervical spine injury in children after blunt trauma. AB - STUDY OBJECTIVE: Cervical spine injuries in children are rare. However, immobilization and imaging for potential cervical spine injury after trauma are common and are associated with adverse effects. Risk factors for cervical spine injury have been developed to safely limit immobilization and radiography in adults, but not in children. The purpose of our study is to identify risk factors associated with cervical spine injury in children after blunt trauma. METHODS: We conducted a case-control study of children younger than 16 years, presenting after blunt trauma, and who received cervical spine radiographs at 17 hospitals in the Pediatric Emergency Care Applied Research Network (PECARN) between January 2000 and December 2004. Cases were children with cervical spine injury. We created 3 control groups of children free of cervical spine injury: (1) random controls, (2) age and mechanism of injury-matched controls, and (3) for cases receiving out-of-hospital emergency medical services (EMS), age-matched controls who also received EMS care. We abstracted data from 3 sources: PECARN hospital, referring hospital, and out-of-hospital patient records. We performed multiple logistic regression analyses to identify predictors of cervical spine injury and calculated the model's sensitivity and specificity. RESULTS: We reviewed 540 records of children with cervical spine injury and 1,060, 1,012, and 702 random, mechanism of injury, and EMS controls, respectively. In the analysis using random controls, we identified 8 factors associated with cervical spine injury: altered mental status, focal neurologic findings, neck pain, torticollis, substantial torso injury, conditions predisposing to cervical spine injury, diving, and high risk motor vehicle crash. Having 1 or more factors was 98% (95% confidence interval 96% to 99%) sensitive and 26% (95% confidence interval 23% to 29%) specific for cervical spine injury. We identified similar risk factors in the other analyses. CONCLUSION: We identified an 8-variable model for cervical spine injury in children after blunt trauma that warrants prospective refinement and validation. PMID- 21035908 TI - Papillary squamous cell carcinoma of the head and neck: a clinicopathologic series. AB - PURPOSE: Papillary squamous cell carcinoma (PSCC) is a rare malignancy that has been associated with human papillomavirus. We present all cases of this disease at a single academic teaching hospital over the last 30 years. MATERIALS AND METHODS: A retrospective chart review was performed for all patients with a diagnosis of PSCC. Of 65 patients identified, 52 were included after meeting established diagnostic criteria. Chart reviews were performed for patient demographics, overall survival, and disease-free survival. RESULTS: Mean age at diagnosis was 65 years, with a male to female ratio of 2.3:1. The majority of lesions (n = 34, 65.4%) arose in areas commonly affected by benign squamous papillomas, with the laryngopharynx the most commonly affected (n = 19, 36.5%), followed by the oral cavity (n = 18, 34.6%), sinonasal tract (n = 8, 15.4%), and oropharynx (n = 7, 13.5%). Two- and 5-year disease-free survival rate was 68% and 46%, respectively. Overall survival rate was 90% and 72% at 2 and 5 years, respectively. CONCLUSIONS: Papillary squamous cell carcinoma of the head and neck is a distinct variant of conventional squamous cell carcinoma with a good prognosis despite high locoregional recurrence rates. Histology and subsite localization corroborate existing evidence that human papillomavirus may be involved. PMID- 21035909 TI - Argon plasma coagulation versus cold dissection in pediatric tonsillectomy. AB - PURPOSE: Argon plasma coagulation (APC) is a new surgical procedure based on a conductive plasma of ionized argon between an activating electrode and a tissue surface. It is a good alternative for tonsillectomy because of its effective hemostasis and limited penetration depth of the coagulation beam. The aim of this prospective, randomized trial was to evaluate the operative time, intraoperative bleeding, and postoperative morbidity of the "hot" APC tonsillectomy compared with a traditional "cold" dissection tonsillectomy in children. MATERIALS AND METHODS: Two hundred eighteen pediatric patients (aged 4-15 years; mean, 7,2 years) were randomized into 2 groups: treatment A (tonsillectomy with APC, n = 109) and treatment B (conventional tonsillectomy, n = 109). The outcome measures were as follows: (1) operative time, (2) intraoperative blood loss, (3) postoperative pain (evaluated using a visual analogue scale with a range score 0 10 on postoperative days 1, 3, 5, 8, and 15), and (4) postoperative primary and secondary hemorrhage. Statistical analysis was carried out using the Student t test. RESULTS: In treatment A group, the mean duration of operative time and the intraoperative blood loss were significantly reduced (P < .001). There was no statistical significant difference between 2 groups in the intensity of postoperative pain and the incidence of postoperative hemorrhage (P > .05). CONCLUSIONS: Argon plasma coagulation tonsillectomy in children is a new, easy, and safe technique that offers a complete eradication of the tonsillar disease, short operating time, minimal intraoperative blood loss, and a suitable cost with no additional increase in postoperative pain and hemorrhage when compared with the conventional "cold dissection." PMID- 21035911 TI - First branchial arch fistula: diagnostic dilemma and improvised surgical management. AB - First branchial cleft anomalies are uncommon, and only sporadic case reports are published in the literature. They account for 1% to 8% of all the branchial abnormalities. The often variable presentation and tract siting of first arch fistulae have led to misdiagnosis. The misdiagnosis results in inappropriate/ineffective treatment and recurrence of the sinus tract. We present a 19-year-old woman who presented to the ENT outpatient department with episodic discharge from a long-standing fistula anterior to the left sternomastoid muscle. This was associated with repeated episodes of ipsilateral tonsillitis. In relation to the history and because of the position of the fistula, a diagnosis of second branchial arch fistula was made. An attempt at excision was unfortunately followed by early recurrence of discharge. At review following the procedure, a defect of the left tympanic membrane in the form of a fibrous band was noted, and a revised diagnosis of first branchial arch sinus was made. Wide surgical excision of the tract with partial parotidectomy was performed. An uneventful postoperative course followed, with no recurrence of symptoms after 24 months of review. We discuss the case, the diagnostic pathway, and the wide local excision technique used for removal of branchial fistulae. PMID- 21035912 TI - Treatment of sleep-disordered breathing: a concern. PMID- 21035913 TI - "Pediatric chronic rhinosinusitis: a retrospective review" by Criddle et al. PMID- 21035914 TI - Penetrating neck trauma: a case for conservative approach. AB - BACKGROUND: Selective conservative management of penetrating neck trauma is a commonly adopted procedure to manage patients of such trauma. However, at places where trauma services are inadequate on different counts and a low-intensity military conflict is on, relevance of this approach without compromising the safety and well-being of the patient remains to be evaluated. OBJECTIVES: The study aimed to address the relevance of selective conservative management of penetrating neck trauma in a low-intensity military conflict of Kashmir. PATIENTS AND METHODS: This was a prospective case study of patients presenting to the ENT Head & Neck Surgery department with penetrating neck trauma for a 2-year period from June 2003 to May 2005. After a careful physical examination in the emergency room, immediate surgical intervention or a careful observation is planned. Relevant investigations in the latter group if indicated by clinical examination determined whether to operate or to continue such approach. The data were collected and analyzed. RESULTS: Forty-six patients fulfilled the criteria to be included in the study. Eight patients (17.4%) underwent immediate surgical intervention, whereas the remaining patients (78.26%) were carefully observed for a minimum of 24 hours. Two patients of the active observation group required delayed exploration because of the close proximity of projectile to vessels. None of the patients in either group died. There was significant difference between the 2 groups in terms of hospital stay, use of diagnostic tests, and complications. CONCLUSIONS: Selective conservative management is a cost-effective approach for penetrating neck trauma even in areas where there is relative paucity of advanced trauma services. These results further reinforce the validity of careful physical examination as a reliable tool to guide further management without necessarily resorting to expensive and at times difficult to do diagnostic tests. PMID- 21035915 TI - Metastatic basal cell carcinoma. AB - OBJECTIVE: The purpose of this study is to review our series of metastatic basal cell carcinomas of the head and neck. STUDY DESIGN: A retrospective review was conducted for this study. METHODS: All cases of documented metastatic basal cell carcinomas arising from a primary within the head and neck region and presenting for treatment to one of the authors (Y.D.) were included in this review. RESULTS: Nine patients were available for review. Five patients had extension to but not transgression of the base of skull. Sites for metastatic disease included 4 lungs and 5 parotid glands. All metastatic lesions were treated with surgical excision, and 6 also received postoperative radiation therapy. No patient deaths from disease have been noted at an average follow-up of 4.7 years (range, 3-8.5 years). No evidence of further metastatic disease has been noted in any of these patients on follow-up. CONCLUSIONS: Metastatic basal cell carcinoma arising from a head and neck primary is a rare entity. However, initial involvement of the skull base and/or dura by a basal cell carcinoma appears to warrant a complete metastatic workup and metastatic surveillance. When metastatic disease is discovered, it appears to be well treated by surgical resection with/without adjunctive radiation therapy. We do not favor chemotherapy for resectable basal cell carcinomas. PMID- 21035916 TI - Iatrogenic pseudoaneurysm: a rare complication of sinonasal surgery. AB - OBJECTIVE: We report 2 patients with iatrogenic pseudoaneurysms, which developed following sinus surgery. METHOD: Case reports and a review of literature of the management of iatrogenic pseudoaneurysm. RESULTS: For one patient who presented with massive epistaxis, the only lifesaving option available was to perform an urgent angiogram followed by selective embolization of the feeding vessel. In the second patient who presented with persistent nasal obstruction and discharge and no epistaxis, a traumatic aneurysm of the internal carotid artery was demonstrated on magnetic resonance imaging scan that was later confirmed by angiography; he, however, declined further treatment. CONCLUSION: Iatrogenic pseudoaneurysms that develop following a vascular injury, though rare, can cause life-threatening epistaxis or a thromboembolism. In this report, we describe 2 different manifestations of iatrogenic vascular malformations following sinus surgery. The role of angiography and subsequent endovascular therapy in the management of these lesions is emphasized. PMID- 21035917 TI - Preoperative magnetic resonance imaging protocol for endoscopic cranial base image-guided surgery. AB - OBJECTIVE: Despite the increasing utilization of image-guided surgery, no radiology protocols for obtaining magnetic resonance (MR) imaging of adequate quality are available in the current literature. At our institution, more than 300 endonasal cranial base procedures including pituitary, extended pituitary, and other anterior skullbase procedures have been performed in the past 3 years. To facilitate and optimize preoperative evaluation and assessment, there was a need to develop a magnetic resonance protocol. METHODS: Retrospective Technical Assessment was performed. DISCUSSION: Through a collaborative effort between the otolaryngology, neurosurgery, and neuroradiology departments at our institution, a skull base MR image-guided (IGS) protocol was developed with several ends in mind. First, it was necessary to generate diagnostic images useful for the more frequently seen pathologies to improve work flow and limit the expense and inefficiency of case specific MR studies. Second, it was necessary to generate sequences useful for IGS, preferably using sequences that best highlight that lesion. Currently, at our institution, all MR images used for IGS are obtained using this protocol as part of preoperative planning. The protocol that has been developed allows for thin cut precontrast and postcontrast axial cuts that can be used to plan intraoperative image guidance. It also obtains a thin cut T2 axial series that can be compiled separately for intraoperative imaging, or may be fused with computed tomographic images for combined modality. The outlined protocol obtains image sequences effective for diagnostic and operative purposes for image-guided surgery using both T1 and T2 sequences. PMID- 21035918 TI - Expression of nonclassical molecule human leukocyte antigen-G in oral lesions. AB - INTRODUCTION: Human leukocyte antigen (HLA)-G is a nonclassic class I molecule that acts as a modulator of immune responses, and the expression of these molecules in virus-infected cells has been associated with subversion of the immune response. OBJECTIVE: In this study, we performed a cross-sectional study, systematically comparing the expression of the HLA-G in benign, premalignant, and malignant oral lesions and correlating it with the presence of high-risk and low risk human papillomavirus (HPV) types. SPECIMENS AND METHODS: Oral biopsies were collected from 51 patients and analyzed by immunohistochemistry using anti-HLA-G antibody. Human papillomavirus detection and typing from oral biopsies were obtained by polymerase chain reaction using GP5+/GP6+ and specific primers. RESULTS: The 51 biopsies were stratified into 3 groups according to lesion grade: oral benign lesions (oral hyperplasia and papilloma, n = 16), oral premalignant lesions (oral leukoplakia with dysplasia and lichen planus, n = 17), and malignant lesions (oral squamous cell carcinoma, n = 18). Human leukocyte antigen G overexpression was mainly observed in benign and premalignant oral lesions but was not related to HPV infection (P > .05). On the other hand, HPV DNA was detected in 24 (47%) oral lesions, mainly in benign and premalignant lesions, with the most frequent type detected being high-risk HPV type. CONCLUSION: The HLA-G molecule was expressed in a significant number of benign oral lesions and was not correlated with HPV infection or oral cancer. PMID- 21035920 TI - Efficacy of concurrent application of chlorhexidine gluconate and povidone iodine against six nosocomial pathogens. AB - BACKGROUND: Chlorhexidine gluconate (CHG) and povidone iodine (PI) are rarely used concurrently despite a lack of evidence regarding functional incompatibility of these agents. METHODS: CHG and PI, alone and combined, were evaluated against Staphylococcus aureus (methicillin-susceptible S aureus [MSSA] and methicillin resistant S aureus [MRSA]), Staphylococcus epidermidis (MRSE), Acinetobacter baumannii, Pseudomonas aeruginosa, and Escherichia coli using checkerboard microbroth dilution techniques. Minimum bactericidal concentration (MBC) was the concentration (percent wt/vol) that reduced bacterial burden >= 5-log(10) colony forming units/mL at 2 hours when compared with bacterial densities in growth controls. Fractional bactericidal concentration indexes (FBCIs) were calculated to determine CHG and PI compatibility. Additionally, tissue plugs from freshly excised porcine vaginal mucosa were infected with S aureus (MSSA), treated for 2 hours with CHG 3%, PI 5%, or CHG 3% and PI 5% combined and then viable bacteria on the tissue plugs enumerated. RESULTS: In broth, CHG demonstrated dose dependent bactericidal activity, whereas PI activity was all-or-none. All isolates studied were similarly susceptible to CHG (MBCs: 0.0078% +/- 0.0019%, 0.0069% +/- 0.0026%, 0.0024% +/- 0.0005%, 0.0024% +/- 0.0005%, 0.0059% +/- 0.0%, and 0.0029% +/- 0.0%, respectively). The MBCs of PI were identical (0.625%) for all isolates. Overall, FBCI calculations showed indifference. Treatment of MSSA infected porcine tissue for 2 hours demonstrated that the CHG-PI combination was superior to either antiseptic alone. CONCLUSION: FBCIs, determined in broth culture, indicate that combining CHG and PI had no negative impact on antisepsis. Moreover, data from an ex vivo porcine mucosal infection model suggest a potential benefit when combining the 2 antiseptic agents. PMID- 21035919 TI - Epidemiologic, clinical characteristics, and risk factors for adverse outcome in multiresistant gram-negative primary bacteremia of critically ill patients. AB - BACKGROUND: Characteristics and burden of primary bacteremia because of multidrug resistant (MDR) gram-negative bacteria (GNB) in intensive care unit (ICU) patients remain understudied. METHODS: A cohort study of patients with primary MDR GNB-related bacteremia from the ICU of a tertiary Greek hospital during a 3 year period was conducted for recognition of clinical characteristics and risk factors for adverse outcome. A case-control study was further performed to evaluate risk factors for development of MDR GNB-related primary bacteremia. RESULTS: Fifty monomicrobial episodes of primary bacteremia because of Klebsiella pneumoniae (n = 20), Acinetobacter baumannii (n = 18), and Pseudomonas aeruginosa (n = 12) were recorded. The presence of diabetes mellitus was the only significant risk factor for development of MDR GNB-related primary bacteremia. Most episodes (78%) were ICU acquired in patients with prolonged mechanical ventilation and previous hospitalization in the ward. Mortality was 47.6% vs 19% of controls, P = .01. Mortality was higher in recurrent bacteremia (62.5%). Mortality was statistically associated with age (P = .002) and degree of multiorgan dysfunction expressed by sequential organ failure assessment score on day of bacteremia documentation (P = .001). CONCLUSION: Critically ill patients with MDR GNB-related primary bacteremia present significant mortality mainly associated with age and multiorgan failure. A baumanii bacteremia confers significant mortality compared with the benign course of K pneumoniae in such settings. Diabetes mellitus is a risk factor for development of such episodes, which may, in part, be general ward acquired, underlining the need for expanded vigilance. PMID- 21035921 TI - Isochaihulactone analogues: synthesis and anti-proliferative activity of novel dibenzylbutyrolactones. AB - A series of dibenzyl-gamma-butyrolactones bearing a hydroxyl group at the benzylic position of 3-benzyl group were synthesized as hydrated analogue of isochaihulactone and evaluated against breast cancer human cell lines (MDA-M231, MCF-7 and T47D). The target compounds were synthesized in 7 steps from known lactone; (S)-(+)-gamma-benzyloxymethyl-gamma-butyrolactone. The key step was the aldol condensation between (+)-(R)-beta-(benzo[d][1,3]dioxol-5-ylmethyl)-gamma butyrolactone and substituted benzaldehydes which afforded corresponding alpha hydroxybenzyl butyrolactone analogues. The cytotoxic study of the synthesized compounds against breast cancer human cell lines showed that some of them inhibit breast cancer human cell proliferation with percentage inhibitions over 50% at concentrations less than 50 MUg/mL. PMID- 21035922 TI - Synthesis, NMR characterization and in vitro cytotoxicity evaluation of new poly(oxyethylene aminophosphonate)s. AB - The synthesis of four novel poly(oxyethylene aminophosphonate)s through an addition of poly(oxyethylene H-phosphonate)s to N-(4-dimethylaminobenzylidene)-p toluidine or N-furfurylidene-p-toluidine is reported. The IR and 1H, 13C and 31P NMR data of the poly(aminophosphonate)s are given. The polymers consist of aminophosphonate and poly(ethylene glycol) (PEG) units only. They are expected to act in vivo as prodrugs of the aminophosphonates and will be interesting as a new class of biodegradable polymer drug carriers. The cytotoxicity of the synthesized poly(aminophosphonate)s and two previously described analogues, was tested against a panel of human tumor cell lines, using cisplatin as reference cytotoxic agent. The presence of 2-furyl-p-toluidino moiety with a longer PEG (13 units) chain were identified as structural prerequisites affording superior activity, while the analogues originating from the Schiff bases N-(4 dimethylaminobenzylidene)-p-toluidine and N,N-dimethyl-N'-furfurylidene-1,3 diaminopropane were generally less active. In all sub-series of polymers the reduction of the PEG chain length from 13 to 4 units led to a significant reduction in relative potency. The established cytotoxicity, which in most of the polymers was comparable to that of cisplatin give us reason to consider the presented polymers as a novel class of aminophosphonate-based cytotoxic agents. PMID- 21035923 TI - [Antiplatelet agents: which one, when and for whom?]. PMID- 21035924 TI - [Hypokalemia induced quadriparesis as the presenting manifestation of Gougerot Sjogren's syndrome]. AB - We report a 30-year-old woman who presented with a hypokaliemia-related subacute quadriparesis. The various causes of hypokalemia induced paresis were discussed but the association of hypokalemia with metabolic acidosis and normal anion gap was diagnostic of distal renal tubular acidosis. The renal tubulopathy was the presenting manifestation of a primary Sjogren's syndrome. Distal renal tubular acidosis concerns a third of the patients affected by this auto-immune disease. PMID- 21035925 TI - [Pathogenic mechanisms of autoimmune diseases]. PMID- 21035926 TI - [Chronic intestinal pseudo-obstruction in systemic lupus erythematosus]. AB - Intestinal pseudo-obstruction (IPO) is an uncommon and severe complication of systemic lupus erythematosus (SLE). We report a 24-year-old female with a 2 year SLE duration who presented with abdominal pain, vomiting, constipation and abdominal distention. Plain abdominal radiograph showed multiple air-fluid levels of the small bowel. Computed tomographic scan of the abdomen revealed dilated small bowel loops without mechanical obstruction. Urinary tract involvement was also demonstrated. IPO was diagnosed and the patient responded well to immunosuppressive treatment. IPO is a recently recognized manifestation of SLE that may be the presenting manifestation of the systemic disease or occur more commonly during disease course. Early recognition of IPO is necessary to institute appropriate medical treatment and to avoid inappropriate surgical intervention. PMID- 21035927 TI - Hand grip strength: outcome predictor and marker of nutritional status. AB - BACKGROUND & AIMS: Among all muscle function tests, measurement of hand grip strength has gained attention as a simple, non-invasive marker of muscle strength of upper extremities, well suitable for clinical use. This review outlines the prognostic relevance of grip strength in various clinical and epidemiologic settings and investigates its suitability as marker of nutritional status in cross-sectional as well as intervention studies. METHODS: Studies investigating grip strength as prognostic marker or nutritional parameter in cross-sectional or intervention studies were summarized. RESULTS AND CONCLUSIONS: Numerous clinical and epidemiological studies have shown the predictive potential of hand grip strength regarding short and long-term mortality and morbidity. In patients, impaired grip strength is an indicator of increased postoperative complications, increased length of hospitalization, higher rehospitalisation rate and decreased physical status. In elderly in particular, loss of grip strength implies loss of independence. Epidemiological studies have moreover demonstrated that low grip strength in healthy adults predicts increased risk of functional limitations and disability in higher age as well as all-cause mortality. As muscle function reacts early to nutritional deprivation, hand grip strength has also become a popular marker of nutritional status and is increasingly being employed as outcome variable in nutritional intervention studies. PMID- 21035928 TI - UK-born ethnic minority women and their experiences of feeding their newborn infant. AB - OBJECTIVE: to explore the factors that impact on UK-born ethnic minority women's experiences of and decisions around feeding their infant. DESIGN: in-depth semi structured interviews. PARTICIPANTS: 34 UK-born women of Black African, Black Caribbean, Pakistani, Bangladeshi, Indian and Irish parentage and 30 health-care professionals. SETTING: women and health-care professionals were recruited primarily from hospitals serving large numbers of ethnic minority women in London and Birmingham. FINDINGS AND CONCLUSIONS: despite being aware of the benefits of exclusive breast feeding, many women chose to feed their infant with formula. The main barriers to breast feeding were the perceived difficulties of breast feeding, a family preference for formula feed, and embarrassment about breast feeding in front of others. Reports from women of South Asian parentage, particularly those who lived with an extended family, suggested that their intentions to breast feed were compromised by the context of their family life. The lack of privacy in these households and grandparental pressure appeared to be key issues. Unlike other participants, Irish women reported an intention to feed their infant with formula before giving birth. The key facilitators to breast feeding were the self-confidence and determination of women and the supportive role of health-care professionals. IMPLICATIONS FOR PRACTICE: these findings point to common but also culturally specific mechanisms that may hinder both the initiation and maintenance of breast feeding in UK-born ethnic minority women. They signal potential benefits from the inclusion of family members in breast feeding support programmes. PMID- 21035930 TI - Effects of biochar and the earthworm Eisenia fetida on the bioavailability of polycyclic aromatic hydrocarbons and potentially toxic elements. AB - Polycyclic aromatic hydrocarbons (PAHs) and potentially toxic elements (PTEs) were monitored over 56 days in calcareous contaminated-soil amended with either or both biochar and Eisenia fetida. Biochar reduced total (449 to 306 mg kg(-1)) and bioavailable (cyclodextrin extractable) (276 to 182 mg kg(-1)) PAHs, PAH concentrations in E. fetida (up to 45%) but also earthworm weight. Earthworms increased PAH bioavailability by >40%. Combined treatment results were similar to the biochar-only treatment. Earthworms increased water soluble Co (3.4 to 29.2 mg kg(-1)), Cu (60.0 to 120.1 mg kg(-1)) and Ni (31.7 to 83.0 mg kg(-1)) but not As, Cd, Pb or Zn; biochar reduced water soluble Cu (60 to 37 mg kg(-1)). Combined treatment results were similar to the biochar-only treatment but gave a greater reduction in As and Cd mobility. Biochar has contaminated land remediation potential, but its long-term impact on contaminants and soil biota needs to be assessed. PMID- 21035929 TI - Multiple sclerosis affects the frequency content in the vertical ground reaction forces during walking. AB - BACKGROUND: Multiple sclerosis is a progressive neurological disease that results in a high incident of gait disturbance. Exploring the frequency content of the ground reaction forces generated during walking may provide additional insights to gait in patients with multiple sclerosis that could lead to specific tools for differential diagnosis. The purpose of this study was to investigate differences in the frequency content of these forces in an effort to contribute to improved clinical management of this disease. METHODS: Eighteen patients and eighteen healthy controls walked across a 10 meter long walkway. The anterior-posterior and vertical ground reaction forces generated during the stance phase of gait were evaluated in the frequency domain using fast Fourier transformation. T-tests were utilized for comparison of median frequency, the 99.5% frequency, and the frequency bandwidth between patients and healthy controls and also for comparisons between patients with mild and moderate severity. FINDINGS: Patients with multiple sclerosis had significantly lower 99.5% frequency (P=0.006) and median frequency (P<0.001) in the vertical ground reaction force. No differences were found in the anterior-posterior reaction force frequency content. There were no differences between patients with mild and moderate severity. INTERPRETATION: The lower frequency content suggests lesser vertical oscillation of the center of gravity. Lack of differences between severities may suggest presence of differences prior to currently established diagnosis timelines. Analysis of the frequency content may potentially serve to provide earlier diagnostic assessment of this debilitating disease. PMID- 21035931 TI - Toxicity profile of labile preservative bronopol in water: the role of more persistent and toxic transformation products. AB - Transformation products usually differ in environmental behaviors and toxicological properties from the parent contaminants, and probably cause potential risks to the environment. Toxicity evolution of a labile preservative, bronopol, upon primary aquatic degradation processes was investigated. Bronopol rapidly hydrolyzed in natural waters, and primarily produced more stable 2-bromo 2-nitroethanol (BNE) and bromonitromethane (BNM). Light enhanced degradation of the targeted compounds with water site specific photoactivity. The bond order analysis theoretically revealed that the reversible retroaldol reactions were primary degradation routes for bronopol and BNE. Judging from toxicity assays and the relative pesticide toxicity index, these degradation products (i.e., BNE and BNM), more persistent and higher toxic than the parent, probably accumulated in natural waters and resulted in higher or prolonging adverse impacts. Therefore, these transformation products should be included into the assessment of ecological risks of non-persistent and low toxic chemicals such as the preservative bronopol. PMID- 21035932 TI - Prediction of ESRD and death among people with CKD: the Chronic Renal Impairment in Birmingham (CRIB) prospective cohort study. AB - BACKGROUND: Validated prediction scores are required to assess the risks of end stage renal disease (ESRD) and death in individuals with chronic kidney disease (CKD). STUDY DESIGN: Prospective cohort study with validation in a separate cohort. SETTING & PARTICIPANTS: Cox regression was used to assess the relevance of baseline characteristics to risk of ESRD (mean follow-up, 4.1 years) and death (mean follow-up, 6.0 years) in 382 patients with stages 3-5 CKD not initially on dialysis therapy in the Chronic Renal Impairment in Birmingham (CRIB) Study. Resultant risk prediction equations were tested in a separate cohort of 213 patients with CKD (the East Kent cohort). FACTORS: 44 baseline characteristics (including 30 blood and urine assays). OUTCOMES: ESRD and all-cause mortality. RESULTS: In the CRIB cohort, 190 patients reached ESRD (12.1%/y) and 150 died (6.5%/y). Each 30% lower baseline estimated glomerular filtration rate was associated with a 3-fold higher ESRD rate and a 1.3-fold higher death rate. After adjustment for each other, only baseline creatinine level, serum phosphate level, urinary albumin-creatinine ratio, and female sex remained strongly (P < 0.01) predictive of ESRD. For death, age, N-terminal pro-brain natriuretic peptide, troponin T level, and cigarette smoking remained strongly predictive of risk. Using these factors to predict outcomes in the East Kent cohort yielded an area under the receiver operating characteristic curve (ie, C statistic) of 0.91 (95% CI, 0.87-0.96) for ESRD and 0.82 (95% CI, 0.75-0.89) for death. LIMITATIONS: Other important factors may have been missed because of limited study power. CONCLUSIONS: Simple laboratory measures of kidney and cardiac function plus age, sex, and smoking history can be used to help identify patients with CKD at highest risk of ESRD and death. Larger cohort studies are required to further validate these results. PMID- 21035934 TI - Predoctoral dental education and the future of oral and maxillofacial surgery. PMID- 21035933 TI - Tubular transport: core curriculum 2010. PMID- 21035935 TI - Embrasure wires for intraoperative maxillomandibular fixation are rapid and effective. AB - PURPOSE: The management of some mandible fractures requires maxillomandibular fixation (MMF) intraoperatively but not postoperatively. Intraoperative MMF with arch bars has significant disadvantages, including duration of application and risk of disease transmission. Some surgeons have sought to minimize these disadvantages, improve efficiency, and decrease cost by omitting formal MMF altogether and manually stabilizing the occlusion. Embrasure wires are a method of intraoperative MMF with significant potential advantages. The purpose of this investigation was to compare embrasure wires with Erich arch bars (Karl Leibinger Co, Mulheim, Germany) for intraoperative stabilization of mandible fractures. PATIENTS AND METHODS: This retrospective case review comprised 50 patients with a primary diagnosis of mandible fracture requiring open reduction-internal fixation with intraoperative MMF. Patients were categorized into 2 groups: intraoperative MMF using embrasure wires (group A) or intraoperative MMF using arch bars (group B). In each group the time required to place the MMF was recorded in whole minutes. The success or failure of the technique to maintain stable MMF throughout the procedure was assessed. RESULTS: Intraoperative MMF was used with embrasure wires in 27 of 50 patients (54%) and with arch bars in 23 of 50 (46%). The mean time required for placement of embrasure wire MMF (2.51 minutes) was significantly (P < .001) less than the mean time required for placement of arch bar MMF (25.47 minutes). The quality of MMF was judged to be stable for the duration of fixation in 24 of 27 patients (89%) in the embrasure wire MMF group and 22 of the 23 patients (96%) in the arch bar group. This difference was not significant (P = .61). CONCLUSION: Embrasure wires can be placed in significantly less time than arch bars, and they provide a reliable form of intraoperative MMF during mandible fracture repair. For intraoperative MMF, embrasure wires offer significant advantages compared with arch bars by reducing application time. In addition, embrasure wires may reduce the risk of disease transmission by decreasing the number of wires required for MMF. PMID- 21035936 TI - The handedness of imagined bodies in action and the role of perspective taking. AB - Past research at the nexus of motor control and perception investigated the role of perspective taking in many behavioral and neuroimaging studies. Some investigators addressed the issue of one's own vs. others' action imagination, but the possible effects of a front or a back view in imagining others' actions have so far been neglected. We report two 'single trial' experiments in which a total of 640 participants were asked to imagine a person performing a manual action - either in a front or in a back view - and then to indicate the hand used by the imagined person during movement execution. In such a task, we assume the existence of two distinct biases: a perceptual-mnemonic bias due to subjects' visual experience of others' actions, encouraging them to imagine right-handed movements, and a motor bias due to subjects' experience of self-made actions, encouraging them to imagine movements performed with the same hand as their dominant hand. We hypothesized that a greater involvement of motor representations in the back view compared to the front view could result in an increased correspondence between one's own manual preference and the hand used by the imagined agent in the former condition. The results of both experiments were consistent with this hypothesis, suggesting that while imagining others' actions we employ motor simulations in different degrees according to the perspective adopted. PMID- 21035937 TI - [From Tansini to Angrigiani: improvement and refinement of the thoracodorsal flap]. AB - Flap surgery is the art of transposing an autonomous vascularised tissue, from a donor site to a distant recipient site. It was born 2000 years ago in India, evolving from random flaps to microsurgical flaps with a skeletonised vascular pedicle. This evolution was possible through the knowledge of cutaneous vascularisation and allows today the spreading field of perforator flaps. Writing the story of any particular flap is, in fact, looking back to understand the global concept and evolution of flaps surgery. Therefore the authors detail every step of the development and technical improvement of the thoracodorsal flap from the classical musculocutaneous latissimus dorsi flap to one of its latest achievement, the thoracodorsal perforator flap. This story helps us to appreciate the armamentarium of thin and low donor site morbidity flap that perforator flaps offer to us. PMID- 21035938 TI - Sema4C-Plexin B2 signalling modulates ureteric branching in developing kidney. AB - Semaphorins, originally identified as axon guidance molecules, have also been implicated in angiogenesis, function of the immune system and cancerous growth. Here we show that deletion of Plexin B2 (Plxnb2), a semaphorin receptor that is expressed both in the pretubular aggregates and the ureteric epithelium in the developing kidney, results in renal hypoplasia and occasional double ureters. The rate of cell proliferation in the ureteric epithelium and consequently the number of ureteric tips are reduced in the kidneys lacking Plexin B2 (Plxnb2-/-). Semaphorin 4C, a ligand for Plexin B2, stimulates branching of the ureteric epithelium in wild type and Plxnb2+/- kidney explants, but not in Plxnb2-/- explants. As shown by co-immunoprecipitation Plexin B2 interacts with the Ret receptor tyrosine kinase, the receptor of Glial-cell-line-derived neurotrophic factor (Gdnf), in embryonic kidneys. Isolated Plxnb2-/- ureteric buds fail to respond to Gdnf by branching, but this response is rescued by Fibroblast growth factor 7 and Follistatin as well as by the metanephric mesenchyme. The differentiation of the nephrogenic mesenchyme, its morphology and the rate of apoptosis in the Plxnb2-/- kidneys are normal. Plexin B2 is co-expressed with Plexin B1 (Plxnb1) in the kidney. The double homozygous Plxnb1-Plxnb2-deficient mice show high embryonic lethality prior to onset of nephrogenesis. The only double homozygous embryo surviving to E12 showed hypoplastic kidneys with ureteric branches and differentiating mesenchyme. Taken together, our results show that Sema4C-Plexin B2 signalling regulates ureteric branching, possibly through modulation of Gdnf signalling by interaction with Ret, and suggest non redundant roles for Plexin B1 and Plexin B2 in kidney development. PMID- 21035939 TI - Improvement of soil quality after "alperujo" compost application to two contaminated soils characterised by differing heavy metal solubility. AB - Reclamation of trace element polluted soils often requires the improvement of the soil quality by using appropriate organic amendments. Low quality compost from municipal solid waste has been tested for reclamation of soils, but these materials can provide high amounts of heavy metals. Therefore, a high-quality compost, with low levels of heavy metals, produced from the main by-product of the Spanish olive oil extraction industry ("alperujo") was evaluated for remediation of soils affected by a pyritic mine sludge. Two contaminated soils were selected from the same area: they were characterised by differing pH values (4.6 and 7.3) and total metal concentrations, which greatly affected the fractionation of the metals. Compost was applied to soil at two rates (equivalent to 48 and 72 Tm ha(-1)) and compared with an inorganic fertiliser treatment. Compost acted as an available nutrient source (C, N and P) and showed a low mineralisation rate, suggesting a slow release of nutrients and thus favouring long term soil fertility. In addition, the liming effect of the compost led to a significant reduction of toxicity for soil microorganisms in the acidic soil and immobilisation of soil heavy metals (especially Mn and Zn), resulting in a clear increase in both soil microbial biomass and nitrification. Such positive effects were clearly greater than those provoked by the mineral fertiliser even at the lowest compost application rate, which indicates that this type of compost can be very useful for bioremediation programmes (reclamation and revegetation of polluted soils) based on phytostabilisation strategies. PMID- 21035940 TI - Desorption of two organophosphorous pesticides from soil with wastewater and surfactant solutions. AB - A batch test was used to evaluate the extent of desorption of diazinon and dimethoate, preadsorbed on a calcareous agricultural soil, representative of the Mediterranean area. Urban wastewater from a secondary treatment and seven surfactant solutions, at concentrations ranging from 0.75 mg L(-1) to 10 gL(-1), were used. The surfactants assayed were cationic (hexadecyl trimethyl ammonium bromide (HD)), anionic (sodium dodecyl sulfate (SDS), Aerosol 22 (A22) and Biopower (BP)), and nonionic (Tween 80 (TW), Triton X 100 (TX) and Glucopon 600 (G600)). Desorption of dimethoate was either not affected or only slightly by the nonionic and anionic surfactants tested, while desorption of diazinon from the soil was only enhanced by A22, BP and TW. This desorption increase correlated significantly with the surfactant concentration of the solution used for desorption and with the concurrent increase in the supernatant of the dissolved organic carbon, in particular that originating from the surfactant. This parameter did not vary with the use of SDS, G600 and TX. The cationic surfactant HD was retained on the soil surface, as confirmed by an increase in soil organic carbon, resulting in a fall in desorption rate for both pesticides. Comparing treatment by wastewater with control water, there was no difference in desorption rate for either pesticide. Mixed TW/anionic surfactant solutions either did not modify or slightly increased desorption of both pesticides in comparison with individual surfactant solutions. PMID- 21035941 TI - Five propositions for improving decision making about the environment in developing communities: insights from the decision sciences. AB - Decisions focused on managing natural resources in developing areas present some of the most imposing challenges to policy makers, scientists, and stakeholders alike. The response of policy makers and the technical community in the face of these challenges has been significant. However, our experiences as researchers and facilitators of group planning and decision-making processes have left us concerned about the lack of attention devoted to supporting the underlying processes used to make these complex decisions. To this end, we present five propositions based on work in the decision sciences that we believe stand out as essential for improving decision-making processes in developing communities. PMID- 21035942 TI - Spatial and temporal distribution of polychlorinated biphenyl (PCB) concentrations in soils of an industrialized city in Turkey. AB - Surface soil (0-5 cm) samples from 43 sampling sites covering the entire urban territory of Bursa, an industrialized city in Turkey, were collected in each season and analyzed for 83 polychlorinated biphenyls (PCBs). The mean concentration of total PCBs (Sigma83 PCBs) among all sites over the four seasons was 2121.51 pg/g dry weight (dw), with a range of 207.61-5461.95 pg/g dw. Total PCB concentrations in the soil samples collected near an industrial region were the highest in all seasons. In general, PCB patterns were dominated by low chlorinated homologue groups (<= 5 Cl groups at a 79% level). The predominant homologue group found in Bursa city soils was the penta-CBs (29.1%) followed by the tetra-CBs (25.5%) and tri-CBs (17.6%). A total of seven dioxin-like PCB congeners (CB-77, 81, 105, 114, 118, 123, and 126) were found in every sampling location and their mean total concentration for all locations and seasons was 259.27 pg/g dw, with a range of 7.02-1581.13 pg/g dw. A significant relationship (r = 0.77, p < 0.01) was found between the concentrations of dioxin-like PCBs and the seasonal average sum of PCB concentrations. A correlation between light congeners (= penta-CB) and TOC was found. The pollution potential was assessed based on the values found in soils in different regions in relation to current guideline values. Overall, it was found that PCB levels in the urban soils of Bursa were much lower than both the target values and the values found in most European soils and other regions. PMID- 21035943 TI - Is prostate cancer screening bad or good? Summary of a debate at the innovation in urology meeting, September 17-19, 2010, Milan, Italy. PMID- 21035944 TI - Dogs sniffing urine: a future diagnostic tool or a way to identify new prostate cancer markers? PMID- 21035945 TI - A novel dithiocarbamate analogue with potentially decreased ALDH inhibition has copper-dependent proteasome-inhibitory and apoptosis-inducing activity in human breast cancer cells. AB - Dithiocarbamates are a class of sulfur-based metal-chelating compounds with various applications in medicine. We reported previously that certain members of dithiocarbamates, such as diethyldithiocarbamate, disulfiram (DSF) and pyrrolidine dithiocarbamate (PDTC), were able to bind with tumor cellular copper to inhibit tumor growth through the inhibition of proteasome activity and induction of cancer cell apoptosis. Since the DSF is an irreversible inhibitor of aldehyde dehydrogenase (ALDH), its ALDH-inhibitory activity might potentially affect its usefulness as an anti-cancer drug. For the purpose of selecting potent anti-cancer compounds that are not ALDH inhibitors and mapping out preliminary structure-activity relationship trends for these novel compounds, we synthesized a series of PDTC analogues and chose three novel compounds to study their ALDH inhibitory activity, proteasome-inhibitory activity as well as the cancer cell apoptosis-inducing activity. The results showed that compared to DSF, compound 9 has less ALDH inhibition activity, and the in vitro results also proved the positive effects of 9-Cu in proteasome inhibition and apoptosis induction in breast cancer cells, suggesting that 9 as a lead compound could be developed into a novel proteasome inhibitor anti-cancer drug. PMID- 21035946 TI - Small molecule antagonists for CXCR2 and CXCR1 inhibit human colon cancer liver metastases. AB - CXCR1 and CXCR2 are G-protein coupled receptors, that have been shown to play important role in tumor growth and metastasis, and are prime targets for the development of novel therapeutics. Here, we report that targeting CXCR2 and CXCR1 activity using orally active small molecule antagonist (SCH-527123, SCH-479833) inhibits human colon cancer liver metastasis mediated by decreased neovascularization and enhanced malignant cell apoptosis. There were no differences in primary tumor growth. These studies demonstrate the important role of CXCR2/1 in colon cancer metastasis and that inhibition of CXCR2 and CXCR1, small molecule antagonists provides a novel therapeutic strategy. PMID- 21035948 TI - Relationships between acute toxicities of para nitrophenol (p-NP) and nitrobenzene (NB) to Daphnia magna and Photobacterium phosphoreum: physicochemical properties and metabolites under anaerobic/aerobic sequentials. AB - In this study, the acute toxicities of nitrobenzene (NB) and para nitrophenol (p NP) were investigated in a high rate sequential anaerobic migrating blanket (AMBR)/aerobic completely stirred tank reactor (CSTR) using Microtox and Daphnia magna tests. After sequential anaerobic and aerobic treatments, the inhibitions in the Microtox bacteria decreased from an initial 78.10-48.20% and 4.00%, respectively, in wastewater containing 40.00 mg/L p-NP. The inhibitions of the influent wastewater containing 60.00 mg/L NB decreased from 72.10% to 45.30% and to 4.00% after anaerobic and aerobic treatment, respectively. The acute toxicity removals were 94% and 93% in the effluent of the whole sequential system, for p NP and NB, respectively. The acute toxicity in the influent was dependent on the parent NB and p-NP concentrations and ons their physicochemical properties such as hydrophobicity, octanol/water partition coefficient and vapour density for both Microtox bacteria and Daphnia magna while the toxicity in the effluent of the anaerobic reactor was strongly dependent on the metabolites of p-NP (p-amino phenol, phenol, NH(4)-N) and NB (aniline) for Microtox test. This effluent was not toxic to Daphnia magna. PMID- 21035947 TI - Impact of viral load of hepatitis C on the incidence of hepatocellular carcinoma: A population-based cohort study (JPHC Study). AB - Impact of viral load of HCV on the incidence of hepatocellular carcinoma was investigated using a population-based cohort consisting of 20,794 Japanese. A total of 114 newly arising cases of hepatocellular carcinoma were diagnosed during follow-up. Compared to the hepatitis virus-negative group, the hazard ratio (HR) of developing hepatocellular carcinoma was 35.8-fold higher in HCV monoinfection (95% confidence interval [CI], 20.7-62.7). A titer-dependent increase in risk was not identified. The risk was 3.86-fold higher (CI; 1.73 8.62) for genotype 1 than genotype 2. Our findings suggest that HCV viremia strongly influences the occurrence of hepatocellular carcinoma without titer dependence. PMID- 21035949 TI - Intensive meditation training, immune cell telomerase activity, and psychological mediators. AB - BACKGROUND: Telomerase activity is a predictor of long-term cellular viability, which decreases with chronic psychological distress (Epel et al., 2004). Buddhist traditions claim that meditation decreases psychological distress and promotes well-being (e.g., Dalai Lama and Cutler, 2009). Therefore, we investigated the effects of a 3-month meditation retreat on telomerase activity and two major contributors to the experience of stress: Perceived Control (associated with decreased stress) and Neuroticism (associated with increased subjective distress). We used mediation models to test whether changes in Perceived Control and Neuroticism explained meditation retreat effects on telomerase activity. In addition, we investigated whether two qualities developed by meditative practice, increased Mindfulness and Purpose in Life, accounted for retreat-related changes in the two stress-related variables and in telomerase activity. METHODS: Retreat participants (n=30) meditated for ~6 h daily for 3 months and were compared with a wait-list control group (n=30) matched for age, sex, body mass index, and prior meditation experience. Retreat participants received instruction in concentrative meditation techniques and complementary practices used to cultivate benevolent states of mind (Wallace, 2006). Psychological measures were assessed pre- and post-retreat. Peripheral blood mononuclear cell samples were collected post retreat for telomerase activity. Because there were clear, a priori hypotheses, 1 tailed significance criteria were used throughout. RESULTS: Telomerase activity was significantly greater in retreat participants than in controls at the end of the retreat (p<0.05). Increases in Perceived Control, decreases in Neuroticism, and increases in both Mindfulness and Purpose in Life were greater in the retreat group (p<0.01). Mediation analyses indicated that the effect of the retreat on telomerase was mediated by increased Perceived Control and decreased Neuroticism. In turn, changes in Perceived Control and Neuroticism were both partially mediated by increased Mindfulness and Purpose in Life. Additionally, increases in Purpose in Life directly mediated the telomerase group difference, whereas increases in Mindfulness did not. CONCLUSIONS: This is the first study to link meditation and positive psychological change with telomerase activity. Although we did not measure baseline telomerase activity, the data suggest that increases in perceived control and decreases in negative affectivity contributed to an increase in telomerase activity, with implications for telomere length and immune cell longevity. Further, Purpose in Life is influenced by meditative practice and directly affects both perceived control and negative emotionality, affecting telomerase activity directly as well as indirectly. PMID- 21035951 TI - Psychotropic medication history of inpatient adolescents--is there a rationale for benzodiazepine prescription? AB - We evaluated the pre-hospitalization psychotropic medication of adolescents with different psychiatric disorders, and examined possible differences in medication history in relation to lifetime psychiatric diagnoses of study subjects. The study sample consisted of 300 girls and 208 boys (age 12-17) admitted to psychiatric inpatient hospital between April 2001 and March 2006. The information on drug therapy history and psychiatric diagnoses were obtained from the Schedule for Affective Disorders and Schizophrenia for School Aged Children-Present and Lifetime (K-SADS-PL). Adolescents with drug use disorders had elevated rates of pre-hospitalization prescribed benzodiazepines (BZDs). Antidepressants and antipsychotics were mainly used by depressed and psychotic adolescents. Previously prescribed BZD medication was associated with 3-fold increased rates of sedative abuse or dependence. Girls had been prescribed antidepressants and BZDs statistically significantly more commonly than boys. The results of our study underline the importance of careful consideration of the use of benzodiazepines, especially in the outpatient treatment of adolescents. PMID- 21035952 TI - Real-time study of prostate intrafraction motion during external beam radiotherapy with daily endorectal balloon. AB - PURPOSE: To prospectively investigate intrafraction prostate motion during radiofrequency-guided prostate radiotherapy with implanted electromagnetic transponders when daily endorectal balloon (ERB) is used. METHODS AND MATERIALS: Intrafraction prostate motion from 24 patients in 787 treatment sessions was evaluated based on three-dimensional (3D), lateral, cranial-caudal (CC), and anterior-posterior (AP) displacements. The mean percentage of time with 3D, lateral, CC, and AP prostate displacements>2, 3, 4, 5, 6, 7, 8, 9, and 10 mm in 1 minute intervals was calculated for up to 6 minutes of treatment time. Correlation between the mean percentage time with 3D prostate displacement>3 mm vs. treatment week was investigated. RESULTS: The percentage of time with 3D prostate movement>2, 3, and 4 mm increased with elapsed treatment time (p<0.05). Prostate movement>5 mm was independent of elapsed treatment time (p=0.11). The overall mean time with prostate excursions>3 mm was 5%. Directional analysis showed negligible lateral prostate motion; AP and CC motion were comparable. The fraction of time with 3D prostate movement>3 mm did not depend on treatment week of (p>0.05) over a 4-minute mean treatment time. CONCLUSIONS: Daily endorectal balloon consistently stabilizes the prostate, preventing clinically significant displacement (>5 mm). A 3-mm internal margin may sufficiently account for 95% of intrafraction prostate movement for up to 6 minutes of treatment time. Directional analysis suggests that the lateral internal margin could be further reduced to 2 mm. PMID- 21035950 TI - Blockade of brain angiotensin II AT1 receptors ameliorates stress, anxiety, brain inflammation and ischemia: Therapeutic implications. AB - Poor adaptation to stress, alterations in cerebrovascular function and excessive brain inflammation play critical roles in the pathophysiology of many psychiatric and neurological disorders such as major depression, schizophrenia, post traumatic stress disorder, Parkinson's and Alzheimer's diseases and traumatic brain injury. Treatment for these highly prevalent and devastating conditions is at present very limited and many times inefficient, and the search for novel therapeutic options is of major importance. Recently, attention has been focused on the role of a brain regulatory peptide, Angiotensin II, and in the translational value of the blockade of its physiological AT(1) receptors. In addition to its well-known cardiovascular effects, Angiotensin II, through AT(1) receptor stimulation, is a pleiotropic brain modulatory factor involved in the control of the reaction to stress, in the regulation of cerebrovascular flow and the response to inflammation. Excessive brain AT(1) receptor activity is associated with exaggerated sympathetic and hormonal response to stress, vulnerability to cerebrovascular ischemia and brain inflammation, processes leading to neuronal injury. In animal models, inhibition of brain AT(1) receptor activity with systemically administered Angiotensin II receptor blockers is neuroprotective; it reduces exaggerated stress responses and anxiety, prevents stress-induced gastric ulcerations, decreases vulnerability to ischemia and stroke, reverses chronic cerebrovascular inflammation, and reduces acute inflammatory responses produced by bacterial endotoxin. These effects protect neurons from injury and contribute to increase the lifespan. Angiotensin II receptor blockers are compounds with a good margin of safety widely used in the treatment of hypertension and their anti-inflammatory and vascular protective effects contribute to reduce renal and cardiovascular failure. Inhibition of brain AT(1) receptors in humans is also neuroprotective, reducing the incidence of stroke, improving cognition and decreasing the progression of Alzheimer's disease. Blockade of AT(1) receptors offers a novel and safe therapeutic approach for the treatment of illnesses of increasing prevalence and socioeconomic impact, such as mood disorders and neurodegenerative diseases of the brain. PMID- 21035953 TI - A Phase II trial of neoadjuvant preoperative chemoradiotherapy with S-1 plus irinotecan and radiation in patients with locally advanced rectal cancer: clinical feasibility and response rate. AB - PURPOSE: We aimed to validate our hypothesis that a preoperative chemoradiotherapy regimen with S-1 plus irinotecan is feasible, safe, and active for the management of locally advanced rectal cancer in a single-arm Phase II setting. METHODS AND MATERIALS: Eligible patients had previously untreated, locally advanced rectal adenocarcinoma. Radiotherapy was administered in fractions of 1.8 Gy/d for 25 days. S-1 was administered orally in a fixed daily dose of 80 mg/m2 on Days 1 to 5, 8 to 12, 22 to 26, and 29 to 33. Irinotecan (80 mg/m2) was infused on Days 1, 8, 22, and 29. Four or more weeks after the completion of the treatment, total mesorectal excision with lateral lymph node dissection was performed. The primary endpoint was the rate of completing treatment in terms of feasibility. The secondary endpoints were the response rate and safety. RESULTS: We enrolled 43 men and 24 women in the study. The number of patients who completed treatment was 58 (86.6%). Overall, 46 patients (68.7%) responded to treatment and 24 (34.7%) had a complete histopathologic response. Three patients had Grade 3 leukopenia, and another three patients had Grade 3 neutropenia. Diarrhea was the most common type of nonhematologic toxicity: 3 patients had Grade 3 diarrhea. CONCLUSIONS: A preoperative regimen of S-1, irinotecan, and radiotherapy to the rectum was feasible, and it appeared safe and effective in this nonrandomized Phase II setting. It exhibited a low incidence of adverse events, a high rate of completion of treatment, and an extremely high rate of pathologic complete response. PMID- 21035954 TI - Infant brain tumors: incidence, survival, and the role of radiation based on Surveillance, Epidemiology, and End Results (SEER) Data. AB - PURPOSE: To evaluate the incidence of infant brain tumors and survival outcomes by disease and treatment variables. METHODS AND MATERIALS: The Surveillance, Epidemiology, and End Results (SEER) Program November 2008 submission database provided age-adjusted incidence rates and individual case information for primary brain tumors diagnosed between 1973 and 2006 in infants less than 12 months of age. RESULTS: Between 1973 and 1986, the incidence of infant brain tumors increased from 16 to 40 cases per million (CPM), and from 1986 to 2006, the annual incidence rate averaged 35 CPM. Leading histologies by annual incidence in CPM were gliomas (13.8), medulloblastoma and primitive neuroectodermal tumors (6.6), and ependymomas (3.6). The annual incidence was higher in whites than in blacks (35.0 vs. 21.3 CPM). Infants with low-grade gliomas had the highest observed survival, and those with atypical teratoid rhabdoid tumors (ATRTs) or primary rhabdoid tumors of the brain had the lowest. Between 1979 and 1993, the annual rate of cases treated with radiation within the first 4 months from diagnosis declined from 20.5 CPM to <2 CPM. For infants with medulloblastoma, desmoplastic histology and treatment with both surgery and upfront radiation were associated with improved survival, but on multivariate regression, only combined surgery and radiation remained associated with improved survival, with a hazard ratio for death of 0.17 compared with surgery alone (p = 0.005). For ATRTs, those treated with surgery and upfront radiation had a 12-month survival of 100% compared with 24.4% for those treated with surgery alone (p = 0.016). For ependymomas survival was higher in patients treated in more recent decades (p = 0.001). CONCLUSION: The incidence of infant brain tumors has been stable since 1986. Survival outcomes varied markedly by histology. For infants with medulloblastoma and ATRTs, improved survival was observed in patients treated with both surgery and early radiation compared with those treated with surgery alone. PMID- 21035955 TI - Phase I dose escalation trial of vandetanib with fractionated radiosurgery in patients with recurrent malignant gliomas. AB - PURPOSE: To determine the maximum tolerated dose (MTD) of vandetanib with fractionated stereotactic radiosurgery (SRS) in patients with recurrent malignant gliomas. METHODS AND MATERIALS: Patients with a recurrent malignant glioma and T1 enhancing recurrent tumor <= 6 cm were eligible. Vandetanib was given orally, once per day, 7 days a week, starting at least 7 days before SRS and continued until a dose-limiting toxicity (DLT) or disease progression. The planned vandetanib daily dose was 100 mg, 200 mg, and 300 mg for the cohorts 1, 2, and 3, respectively, and was escalated using a standard 3+3 design. A total SRS dose of 36 Gy, 12 Gy per fraction, was delivered over 3 consecutive days. The MTD was defined as the dose of vandetanib at which less than 33% of patients developed DLTs, defined by the Common Terminology Criteria for Adverse Events (CTCAE) version 3 as any Grade 3 or greater nonhematologic toxicity and Grade 4 or greater hematologic toxicity. RESULTS: Ten patients were treated, 6 on cohort 1 and 4 on cohort 2. Treatment characteristics were: 7 men, 3 women; median age, 40 years (range, 22-72); 7 GBM, 3 anaplastic astrocytoma (AA); median initial radiation (RT) dose, 60 Gy (range, 59.4-70); median interval since initial RT, 14.5 months (range, 7-123); All patients received SRS per protocol. The median follow-up time was 4 months (range, 1-10 months). Median time on vandetanib was 3 months (range 1-11). One of 6 patients in the first cohort developed a DLT of Grade 3 hemothorax while on anticoagulation. The MTD was reached when 2 of the 4 patients enrolled in the second cohort developed DLTs. Six patients had radiographic response, 2 with stable disease. CONCLUSION: The MTD of vandetanib, with SRS in recurrent malignant glioma, is 100 mg daily. Further evaluation of safety and efficacy is warranted. PMID- 21035956 TI - A dose-volume analysis of radiation pneumonitis in non-small cell lung cancer patients treated with stereotactic body radiation therapy. AB - PURPOSE: To examine the rates and risk factors of radiation pneumonitis (RP) in non-small cell lung cancer (NSCLC) patients treated with stereotactic body radiotherapy (SBRT). METHODS AND MATERIALS: Dosimetry records for 251 patients with lymph node-negative Stage I-IIB NSCLC and no prior chest radiation therapy (RT) treated with SBRT were reviewed. Patients were coded on the basis of the presence of at least Grade (G) 2 RP using the Common Toxicity Criteria version 2 criteria. Radiation doses, V5, V10, V20, and mean lung dose (MLD) data points were extracted from the dose-volume histogram (DVH). RESULTS: Median PTV volume was 48 cc. Median prescribed radiation dose was 60 Gy delivered in three fractions to the 80% isodose line. Median age at treatment was 74 years. Median follow-up was 17 months. RP was reported after treatment of 42 lesions: G1 in 19 (8%), G2 in 17 (7%), G3 in 5 (2%), and G4 in 1 (0.4%). Total lung DVHs were available for 143 patients. For evaluable patients, median MLD, V5, V10, and V20 were 4.1 Gy, 20%, 12%, and 4%, respectively. Median MLDs were 4 Gy and 5 Gy for G0-1 and G2-4 groups, respectively (p = 0.14); median V5 was 20% for G0-1 and 24% for G2-4 (p = 0.70); median V10 was 12% in G0-1 and 16% in G2-4 (p = 0.08), and median V20 was 4% in G0-1 and 6.6% in G2-4 (p = 0.05). G2-4 RP was noted in 4.3% of patients with MLD <=4 Gy compared with 17.6% of patients with MLD >4 Gy (p = 0.02), and in 4.3% of patients with V20 <=4% compared with 16.4% of patients with V20 >4% (p = 0.03). CONCLUSION: Overall rate of G2-4 RP in our population treated with SBRT was 9.4%. Development of symptomatic RP in this series correlated with MLD and V20. PMID- 21035957 TI - Margin evaluation in the presence of deformation, rotation, and translation in prostate and entire seminal vesicle irradiation with daily marker-based setup corrections. AB - PURPOSE: To develop a method for margin evaluation accounting for all measured displacements during treatment of prostate cancer. METHODS AND MATERIALS: For 21 patients treated with stereographic targeting marker-based online translation corrections, dose distributions with varying margins and gradients were created. Sets of possible cumulative delivered dose distributions were simulated by moving voxels and accumulating dose per voxel. Voxel motion was simulated consistent with measured distributions of systematic and random displacements due to stereographic targeting inaccuracies, deformation, rotation, and intrafraction motion. The method of simulation maintained measured correlation of voxel motions due to organ deformation. RESULTS: For the clinical target volume including prostate and seminal vesicles (SV), the probability that some part receives <95% of the prescribed dose, the changes in minimum dose, and volume receiving 95% of prescription dose compared with planning were 80.5% +/- 19.2%, 9.0 +/- 6.8 Gy, and 3.0% +/- 3.7%, respectively, for the smallest studied margins (3 mm prostate, 5 mm SV) and steepest dose gradients. Corresponding values for largest margins (5 mm prostate, 8 mm SV) with a clinical intensity-modulated radiotherapy dose distribution were 46.5% +/- 34.7%, 6.7 +/- 5.8 Gy, and 1.6% +/- 2.3%. For prostate-only clinical target volume, the values were 51.8% +/- 17.7%, 3.3 +/- 1.6 Gy, and 0.6% +/- 0.5% with the smallest margins and 5.2% +/- 7.4%, 1.8 +/- 0.9 Gy, and 0.1% +/- 0.1% for the largest margins. Addition of three-dimensional rotation corrections only improved these values slightly. All rectal planning constraints were met in the actual reconstructed doses for all studied margins. CONCLUSION: We developed a system for margin validation in the presence of deformations. In our population, a 5-mm margin provided sufficient dosimetric coverage for the prostate. In contrast, an 8-mm SV margin was still insufficient owing to deformations. Addition of three-dimensional rotation corrections was of minor influence. PMID- 21035958 TI - The American Society for Radiation Oncology's 2010 core physics curriculum for radiation oncology residents. AB - PURPOSE: In 2004, the American Society for Radiation Oncology (ASTRO) published its first physics education curriculum for residents, which was updated in 2007. A committee composed of physicists and physicians from various residency program teaching institutions was reconvened again to update the curriculum in 2009. METHODS AND MATERIALS: Members of this committee have associations with ASTRO, the American Association of Physicists in Medicine, the Association of Residents in Radiation Oncology, the American Board of Radiology (ABR), and the American College of Radiology. Members reviewed and updated assigned subjects from the last curriculum. The updated curriculum was carefully reviewed by a representative from the ABR and other physics and clinical experts. RESULTS: The new curriculum resulted in a recommended 56-h course, excluding initial orientation. Learning objectives are provided for each subject area, and a detailed outline of material to be covered is given for each lecture hour. Some recent changes in the curriculum include the addition of Radiation Incidents and Bioterrorism Response Training as a subject and updates that reflect new treatment techniques and modalities in a number of core subjects. The new curriculum was approved by the ASTRO board in April 2010. We anticipate that physicists will use this curriculum for structuring their teaching programs, and subsequently the ABR will adopt this educational program for its written examination. Currently, the American College of Radiology uses the ASTRO curriculum for their training examination topics. In addition to the curriculum, the committee updated suggested references and the glossary. CONCLUSIONS: The ASTRO physics education curriculum for radiation oncology residents has been updated. To ensure continued commitment to a current and relevant curriculum, the subject matter will be updated again in 2 years. PMID- 21035959 TI - Long-term outcomes of early-stage nasopharyngeal carcinoma patients treated with intensity-modulated radiotherapy alone. AB - PURPOSE: Reports of intensity-modulated radiotherapy (IMRT) for early-stage nasopharyngeal carcinoma (NPC) have been limited. The present study evaluated the long-term survival outcomes and toxicity of early-stage NPC patients treated with IMRT alone. METHODS AND MATERIALS: Between February 2001 and January 2008, 198 early-stage (T1-T2bN0-N1M0) NPC patients had undergone IMRT alone. The data from these patients were retrospectively analyzed. The patients were treated to 68 Gy at 2.27 Gy/fraction prescribed to the planning target volume of the primary nasopharygeal gross tumor volume. The Radiation Therapy Oncology Group scoring system was used to assess the toxicity. RESULTS: At a median follow-up of 50.9 months (range, 12-104), the 5-year estimated disease-specific survival, local recurrence-free survival, and distant metastasis-free survival rate was 97.3%, 97.7%, and 97.8%, respectively. The 5-year local recurrence-free survival rate was 100% for those with Stage T1 and T2a and 94.2% for those with Stage T2b lesions (p = 0.252). The 5-year distant metastasis-free survival rate for Stage T1N0, T2N0, T1N1, and T2N1 patients was 100%, 98.8%, 100%, and 93.8%, respectively (p = .073). All local recurrence occurred in patients with T2b lesions. Five patients developed distant metastasis. Of these 5 patients, 4 had had Stage T2bN1 disease and 1 had had Stage T2bN0 disease with retropharyngeal lymph node involvement. The most common acute toxicities were mainly Grade 1 or 2. At 24 months after IMRT, no Grade 3 or 4 xerostomia had developed, and 62 (96.9%) of 64 evaluated patients were free of trismus; only 2 patients (3.1%) had Grade 1 trismus. Radiation encephalopathy and cranial nerve injury were not observed. CONCLUSIONS: IMRT alone for Stage T1N0, T2N0, T1N1, and T2N1 yielded satisfactory survival outcomes with acceptable toxicity, and no differences were found in survival outcomes among these four subgroups. Patients with Stage T2b lesions might have relatively greater risk of local recurrence and those with T2bN1 disease mighth have a greater risk of distant metastasis. PMID- 21035960 TI - Linear accelerator-based intensity-modulated total marrow irradiation technique for treatment of hematologic malignancies: a dosimetric feasibility study. AB - PURPOSE: To investigate the dosimetric feasibility of linear accelerator-based intensity-modulated total marrow irradiation (IM-TMI) in patients with hematologic malignancies. METHODS AND MATERIALS: Linear accelerator-based IM-TMI treatment planning was performed for 9 patients using the Eclipse treatment planning system. The planning target volume (PTV) consisted of all the bones in the body from the head to the mid-femur, except for the forearms and hands. Organs at risk (OAR) to be spared included the lungs, heart, liver, kidneys, brain, eyes, oral cavity, and bowel and were contoured by a physician on the axial computed tomography images. The three-isocenter technique previously developed by our group was used for treatment planning. We developed and used a common dose-volume objective method to reduce the planning time and planner subjectivity in the treatment planning process. RESULTS: A 95% PTV coverage with the 99% of the prescribed dose of 12 Gy was achieved for all nine patients. The average dose reduction in OAR ranged from 19% for the lungs to 68% for the lenses. The common dose-volume objective method decreased the planning time by an average of 35% and reduced the inter- and intra- planner subjectivity. CONCLUSION: The results from the present study suggest that the linear accelerator-based IM-TMI technique is clinically feasible. We have demonstrated that linear accelerator-based IM-TMI plans with good PTV coverage and improved OAR sparing can be obtained within a clinically reasonable time using the common dose-volume objective method proposed in the present study. PMID- 21035961 TI - A phase II study of radiotherapy and concurrent paclitaxel chemotherapy in breast conserving treatment for node-positive breast cancer. AB - PURPOSE: Administering adjuvant chemotherapy before breast radiotherapy decreases the risk of systemic recurrence, but delays in radiotherapy could yield higher local failure. We assessed the feasibility and efficacy of placing radiotherapy earlier in the breast-conserving treatment course for lymph node-positive breast cancer. METHODS AND MATERIALS: Between June 2000 and December 2004, 44 women with node-positive Stage II and III breast cancer were entered into this trial. Breast conserving surgery and 4 cycles of doxorubicin (60 mg/m(2))/cyclophosphamide (600 mg/m(2)) were followed by 4 cycles of paclitaxel (175 mg/m(2)) delivered every 3 weeks. Radiotherapy was concurrent with the first 2 cycles of paclitaxel. The breast received 39.6 Gy in 22 fractions with a tumor bed boost of 14 Gy in 7 fractions. Regional lymphatics were included when indicated. Functional lung volume was assessed by use of the diffusing capacity for carbon monoxide as a proxy. Breast cosmesis was evaluated with the Harvard criteria. RESULTS: The 5 year actuarial rate of disease-free survival is 88%, and overall survival is 93%. There have been no local failures. Median follow-up is 75 months. No cases of radiation pneumonitis developed. There was no significant change in the diffusing capacity for carbon monoxide either immediately after radiotherapy (p = 0.51) or with extended follow-up (p = 0.63). Volume of irradiated breast tissue correlated with acute cosmesis, and acute Grade 3 skin toxicity developed in 2 patients. Late cosmesis was not adversely affected. CONCLUSIONS: Concurrent paclitaxel chemotherapy and radiotherapy after breast-conserving surgery shortened total treatment time, provided excellent local control, and was well tolerated. PMID- 21035962 TI - The efficacy of radiotherapy in the treatment of orbital pseudotumor. AB - PURPOSE: To review institutional outcomes for patients treated with external-beam radiotherapy (EBRT) for orbital pseudotumor. METHODS AND MATERIALS: This is a single-institution retrospective review of 20 orbits in 16 patients diagnosed with orbital pseudotumor that received EBRT at the University of Oklahoma, Department of Radiation Oncology. Treated patients had a median follow-up of 16.5 months. RESULTS: Fifteen patients (93.7%) were initially treated with corticosteroids. Eight had recurrence after steroid cessation, six were unable to taper corticosteroids completely or partially, and one experienced progression of symptoms despite corticosteroid therapy. Fourteen patients (87.5%) initially responded to radiotherapy indicated by clinical improvement of preradiation symptoms and/or tapering of corticosteroid dose. Mean EBRT dose was 20 Gy (range, 14-30 Gy). Thirteen patients (81.2%) continued to improve after radiation therapy. Patient outcomes were complete cessation of corticosteroid therapy in nine patients (56.3%) and reduced corticosteroid dose in four patients (25%). Radiotherapy did not achieve long-term control for three patients (18.7%), who still required preradiation corticosteroid dosages. Three patients received retreatment(s) of four orbits, of which two patients achieved long-term symptom control without corticosteroid dependence. One patient received retreatment to an orbit three times, achieving long-term control without corticosteroid dependence. No significant late effects have been observed in retreated patients. CONCLUSIONS: Radiotherapy is an effective treatment for acute symptomatic improvement and long-term control of orbital pseudotumor. Orbital retreatment can be of clinical benefit, without apparent increase in morbidity, when initial irradiation fails to achieve complete response. PMID- 21035963 TI - Controlled delivery of glial cell line-derived neurotrophic factor enhances motor nerve regeneration. AB - PURPOSE: To determine the effect of a motor-specific neurotrophic factor, glial derived neurotrophic factor (GDNF) on motor nerve regeneration. METHODS: We used a nerve conduit filled with a fibrin-based delivery system that provided controlled release of GDNF during nerve regeneration. The motor branch of the rat femoral nerve was used to assess motor nerve regeneration across a 5-mm gap. Four experimental groups (n = 4 to n = 8) were evaluated. These included GDNF with the fibrin-based delivery system (GDNF-DS), fibrin alone, empty conduit (negative control), and nerve isograft (positive control). Nerves were harvested at 5 weeks for analysis by histomorphometry and electron microscopy. RESULTS: At 5 mm distal to the conduit or isografts, the GDNF-DS group was not significantly different from the nerve isograft group in the following histomorphometric measures: total nerve fibers, percentage of neural tissue, and nerve density. Both the GDNF-DS and isograft groups had significantly more fibers and a higher percentage of neural tissue than fibrin alone and empty conduit groups. There were no differences in fiber width among all groups. By electron microscopy, the GDNF-DS and isograft groups also demonstrated more organized nerve architecture than the fibrin alone and empty conduit groups. CONCLUSIONS: The delivery of GDNF from the fibrin-based delivery system promotes motor nerve regeneration at a level similar to an isograft in the femoral motor nerve model. This study gives insight into the potential beneficial role of GDNF in the treatment of motor nerve injuries. PMID- 21035964 TI - Neuralgic amyotrophy: Parsonage-Turner Syndrome. PMID- 21035965 TI - [Behcet's disease in obstetrics and gynecology]. AB - Behcet's disease is a multisystemic disease of unknown origin characterized by a recurrent bipolar aphtosis (oral and genital) associated with vascular, digestive or articular symptoms. Gynecologists can be faced to this disease at any time of the life of their patients, including during the pregnancy. Given that the first demonstrations of the disease can be genital, they are in the front line to evoke this diagnosis. They thus have to know the main characteristics of the disease to make the diagnosis and to organize a multidisciplinary management. During pregnancy, the treatment of the disease is to be adapted to avoid teratogenic drugs, and adapt the doses of the treatment. PMID- 21035966 TI - Multilevel influences of school and family on alcohol-purchasing behaviors in school-aged children. AB - BACKGROUND: Little has been known about children's illegal alcohol purchasing behaviors and associated contextual factors influencing commercial accessibility to alcohol. The aims are to determine multilevel effects of school- and family characteristics on children's alcohol purchase and to probe possible drinking experience-related heterogeneity in such links. METHODS: A representative sample of 2630 4th- and 6th-graders in an urban region of Taiwan in 2007 was drawn via multistage probability sampling. Information about family background and individual drinking experiences was collected via paper-and-pencil self administered questionnaires; school neighborhood characteristics were assessed via commercial datasets of geographic information system. RESULTS: Roughly one in nine 10-12-year-old children ever purchased alcoholic beverages by 6th grade. Children who did not participate in after-school programs or had observed parental drinking had 2-3-fold increased risk to buy alcoholic beverages alone. Living with one or none of parents was associated with alcohol purchase in children who never drank alcohol (Odds Ratio [OR]=3.51; 95% Confidence Interval [CI]=2.14, 5.76). School contextual characteristics have salient effects on minors' alcohol accessibility from commercial sources (e.g., the density of nearby educational institutions, OR=0.33-0.53), and certain school neighborhood effects were notably different by children's drinking experience (e.g., the density of public transportation). CONCLUSIONS: The present study suggests the significant effects of family socioeconomics, family drinking, and school neighboring environment on children's independent alcohol purchase, which may operate differentially by one's drinking experience. Our findings may provide implications that family and school neighborhood contexts should be considered in the devising and delivery of underage drinking prevention programs. PMID- 21035967 TI - Disseminated Rhodococcus equi infection in dromedary camels (Camelus dromedarius). AB - Rhodococcus (R). equi, a recognized pathogen in horses, is emerging as a human opportunistic pathogen, especially in immunocompromized people. It affects also New World camelids, but there are no reports of R. equi infection in Old World camelids yet. Four cases of disseminated R. equi infection in adult breeding dromedaries occurred at one camel farm near Dubai within 16 months of each other. At necropsy the lungs were diffusely consolidated with large caseous areas. Histology revealed severe suppurative to necrotising pneumonia with multiple encapsulated abscesses. Immunohistochemistry enabled the detection of 15- to 17 kDa antigens (VapA) of R. equi in the lung sections. High numbers of R. equi were isolated from the lung lesions as well as from liver, spleen and mediastinal lymph nodes, indicative of septicaemia. The isolated strains were PCR-positive for the specific virulence plasmid (VapA-Gen) of R. equi, indicating virulent strains and containing an 85-kb type I plasmid. This is the first report of disseminated R. equi infection in Old World camelids. Since adult camels in general do not suffer from bacterial caused pneumonia (except tuberculosis), this is a new emerging disease for camels. PMID- 21035968 TI - Phenotypic and genotypic characterization of beta-lactam resistance in Klebsiella pneumoniae isolated from swine. AB - Little is known about the antimicrobial resistance mechanisms in Klebsiella pneumoniae from swine in China. Thus, this paper aims to demonstrate the beta lactam resistance phenotypes and genotypes of K. pneumoniae isolates from swine in southwestern China, detect possible new beta-lactamase variants, and determine whether or not the variants differ in their antibiotic resistance. Isolates from 58 unrelated diseased swine were collected from 61 pig farms in southwestern China from 2007 to 2009. Among the 58 isolates, 75.8-100% were resistant to beta lactam, 62.0-68.97% to fluoroquinolone, 44.8-46.55% to aminoglycoside, and 8.62 17.24% to beta-lactam inhibitors. PCR amplification and DNA sequencing showed that bla(TEM-1) was detected in 100% (n=58) of the isolates, bla(SHV) in 82.76% (n=48), bla(CTX-M) in 39.66% (n=23), and bla(OKP) in 17.24% (n=10). The bla(SHV) types included bla(SHV-1), bla(SHV-11), bla(SHV-12), and bla(SHV-27). None of the isolates harbored bla(KPC), bla(LEN), or bla(GES) gene. Four novel variants (bla(OKP-A-13), bla(OKP-A-14), bla(OKP-A-15), and bla(OKP-A-16)) were identified among the 10 OKP beta-lactamase-producing K. pneumoniae isolates resistant to ampicillin, amoxicillin, oxacillin, cefalexin, and cefadroxil. Plasmid analysis and PCR amplification indicated that bla(TEM-1) genes were detected in the total plasmid. Molecular typing by pulsed-field gel electrophoresis revealed the presence of 10 distinct pulsotypes of OKP producer isolates. Plasmid DNA digested with XbaI yielded two to six bands of ca. 0.15-30 kb. Transformants of the 10 OKP producer isolates showed no differences in their antibiotic susceptibility, except for the pulsotype B transformant, which carried bla(CTX-M). In China, beta lactam resistance appeared to be common among K. pneumoniae isolates from swine, suggesting that K. pneumoniae may be a reservoir for the dissemination of beta lactam resistance among Chinese pig farms. PMID- 21035969 TI - Influence of gonadal hormones on endocrine activity of gonadotroph cells in the adenohypophysis of male lambs during the postnatal transition to puberty. AB - Using histomorphological and functional criteria we describe the feedback mechanisms which could play a role in the regulation of the gonadotrophic axis during the postnatal transition to puberty in male lambs. The working hypothesis was that the testicular factors change the peripheral levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) by influencing the synthesis rate and storage of LH and FSH in adenohypophyseal gonadotroph cells of weanling and weaned pubertal lambs. The examination was made in (i) 9-week-old infantiles, suckling lambs undergoing weaning, testis-intact (TEI) and orchidectomised (ORCHX) at the 6th week of age, and (ii) 16-week-old pubertal lambs TEI and ORCHX at the 12th week of age (n=5 per group). Changes in gonadotrophs were assayed with hybridohistochemistry, immunohistochemistry and radioimmunoassay. The percentage of the adenohypophyseal area (PA) occupied by cells containing LHbeta mRNA and FSHbeta-mRNA and peripheral levels of both gonadotrophins were lower (P<0.01) in the 16-week-old TEI lambs in comparison with the 9-week-old ones. The PA occupied by cells immunoreactive for LHbeta was lower (P<0.01), whereas in the case of FSH was greater (P<0.001) in the 16-week-old lambs. After orchidectomy the PA occupied by gonadotrophs stained for LHbeta-mRNA was greater (P<0.01) in 16-week-old lambs. The PA occupied by LHbeta-labelled cells was lower (P<0.05) in the 9-week-old ORCHX lambs, whereas in 16-week-old ones was higher (P<0.05) in comparison with the TEI lambs. The circulating LH was greater (P<0.01) in the ORCHX 9- and 16-week-old lambs compared to the TEI ones. The PA occupied by cells containing FSHbeta-mRNA and the plasma FSH concentration were greater (P<0.001) after orchidectomy in lambs from both age stages. The PA occupied by FSHbeta labelled cells was greater (P<0.01) in the 9-week-old ORCHX lambs, whereas in 16 week-old ones was lower (P<0.05) compared to the lambs from TEI groups. In conclusion, in infantile lambs testicular factors may play inhibitory role in regulating FSH synthesis rate, storage and release in contrast to the stimulatory role in regulating LH storage reflected by the inhibitory role in regulating LH release. In lambs at the beginning of puberty, testicular factors may play inhibitory role in regulating LH synthesis rate, storage and release in contrast to the stimulatory role in regulating FSH storage reflected by the inhibitory role in regulating FSH synthesis rate and release. The effects of testicular hormones on the gonadotrophin storage, i.e. releasable pools in adenohypophyseal cells, are specific for both LH and FSH in lambs during the postnatal transition to puberty. Thus, the initiation of puberty in male sheep is a function of change of the inhibitory role of gonadal factors in regulating FSH storage to the stimulatory one and the stimulatory role of gonadal factors in regulating LH storage to the inhibitory one. PMID- 21035970 TI - Aberrant CpG methylation of the imprinting control region KvDMR1 detected in assisted reproductive technology-produced calves and pathogenesis of large offspring syndrome. AB - Although somatic cell nuclear transfer (NT) and in vitro fertilization (IVF) have the potential to produce genetically superior livestock, considerable numbers of abnormally large animals, including sheep and cattle affected by "large offspring syndrome" (LOS), have been produced by these assisted reproductive technologies (ART). Interestingly, these phenotypes are reminiscent of Beckwith-Wiedemann syndrome (BWS) in humans, which is an imprinting disorder characterized by pre- and/or postnatal overgrowth. The imprinting control region KvDMR1, which regulates the coordinated expression of growth control genes such as Cdkn1c, is known to be aberrantly hypomethylated in BWS. Therefore, we hypothesized that aberrant imprinting in this region could contribute to LOS. In this study, we analyzed the DNA methylation status of the Kcnq1ot1/Cdkn1c and Igf2/H19 domains on bovine chromosome 29 and examined the coordinated expression of imprinted genes surrounding them in seven calves derived by NT (which showed signs of developmental abnormality), two calves conceived by IVF (both developmentally abnormal), and three conventional calves that died of unrelated causes. Abnormal hypomethylation status at an imprinting control region of Kcnq1ot1/Cdkn1c domain was observed in two of seven NT-derived calves and one of two IVF-derived calves in almost all organs. Moreover, increased expression of Kcnq1ot1 and diminished expression of Cdkn1c were observed by RT-PCR analysis. This study is the first to describe the abnormal hypomethylation of the KvDMR1 domain and subsequent changes in the gene expression of Kcnq1ot1 and Cdkn1c in a subset of calves produced by ART. Our findings provide strong evidence for a role of altered imprinting control in the development of LOS in bovines. PMID- 21035973 TI - Crazy-paving pattern on HRCT of patients with H1N1 pneumonia. PMID- 21035974 TI - Influenza A (H1N1) virus-associated pneumonia: high-resolution computed tomography-pathologic correlation. AB - OBJECTIVE: The purpose of this study was to describe the high-resolution computed tomography (HRCT) features of fatal cases of Influenza A (H1N1) virus-associated pneumonia and to correlate them with pathologic findings. METHODS: The study included six adult patients who died following Influenza A (H1N1) virus associated pneumonia. All patients had undergone HRCT, and the images were retrospectively analyzed by two chest radiologists, who reached decisions by consensus. Two experienced lung pathologists reviewed all pathological specimens. The HRCT findings were correlated with the histopathologic data. RESULTS: The predominant HRCT findings included areas of airspace consolidation (n=6) and ground-glass opacities (n=3). The main pathological features consisted of diffuse alveolar damage with hyaline membrane formation (n=5), associated with various degrees of pulmonary congestion, edema, hemorrhage, inflammatory infiltration and bronchiolitis. A patient who survived longer showed findings of organizing pneumonia. CONCLUSION: Fatal cases of Influenza A (H1N1) virus-associated pneumonia can present as areas of consolidation on CT, with or without ground glass opacities. These abnormalities can be pathologically correlated with diffuse alveolar damage. Patients with longer survival may present with findings of organizing pneumonia. PMID- 21035975 TI - Clinical immunogenicity specificity assessments: a platform evaluation. AB - Immunogenicity assessment is an integral part of the evaluation of the safety and efficacy for protein therapeutics during drug development, and is required by the regulatory authorities. A tiered strategy is typically utilized to assess immunogenicity and is often comprised of a screening method, a confirmation/specificity step and a characterization step. To ensure methods with appropriate sensitivity are utilized, the threshold for screening assays is set to minimize false negatives resulting in a certain rate of false positivity. The confirmatory step is critical for determining assay specificity and eliminating false positives identified in the screening assay. Using a widely implemented technology and bridging assay format commonly used for immunogenicity assessments, unacceptably poor specificity was observed for the confirmatory/specificity step for a subset of monoclonal antibodies in our group. Therefore, we believe that this challenge will be relevant to others in the field. In this paper, we will describe our challenges with one of these antibodies, monoclonal antibody therapeutic X (rhuMAb X). This paper presents extensive evaluation of two technology platforms and various conditions to evaluate and provide solutions to improving the assay specificity in the immunogenicity assessment of antibody therapeutics. PMID- 21035976 TI - Determination of L-dopa, carbidopa, 3-O-methyldopa and entacapone in human plasma by HPLC-ED. AB - The aim of the study was the development of analytical methods suitable for the quantification of L-dopa, carbidopa and entacapone in plasma of Parkinsonian patients treated with Stalevo((r)). The metabolite 3-O-methyldopa was also determined to obtain some indications on the pharmacokinetics of L-dopa. For the simultaneous analysis of L-dopa, 3-O-methyldopa and carbidopa, a RP C18 column as the stationary phase and a mixture of methanol and a pH 2.88 phosphate buffer (8:92, v/v) as the mobile phase were used. A feasible plasma pre-treatment based on protein precipitation was implemented, obtaining extraction yield higher than 94% for all the analytes. For the analysis of entacapone a RP C8 column and a mixture of methanol, acetonitrile and a pH 1.90 phosphate buffer as the mobile phase (17.5:22.5:60, v/v/v) were used. A plasma pre-treatment procedure was developed, based on solid phase extraction of entacapone using Oasis HLB cartridges. Extraction yields were good, being always higher than 96%. Both methods, based on HPLC-ED (V=+0.8V), have been fully validated. Good linearity was obtained over the following concentration ranges: 100-4000 ng mL(-1) for L dopa, 200-10,000 ng mL(-1) for 3-O-methyldopa, 25-4000 ng mL(-1) for carbidopa and 20-4000 ng mL(-1) for entacapone. Precision data were satisfactory, being R.S.D.% values lower than 5.64%; accuracy also resulted very good with recovery data higher than 90%. The proposed methods have been successfully applied to the analysis of patient plasma samples and seem to be suitable for therapeutic drug monitoring purposes. PMID- 21035977 TI - Identification of potential organ donors of advanced age in EDs. AB - OBJECTIVE: In France and in Belgium, as in many countries, there is a shortage of organs for transplantation, which has led to strategies to recruit older potential donors who may die of stroke. METHODS: We conducted a post hoc analysis to identify potential organ donors with cardiac function among a population of dying patients in emergency departments. This population had been selected for a separate multicenter prospective observational study. We identified patients who died of a neurologic cause but had no clinical findings affecting their donor status. RESULTS: Of 2420 patients in the study, 407 died of a neurologic cause; and 233 of these were excluded because of clinical factors that made them ineligible as organ donors. The remaining 174 patients (7.2% of dying patients) could be considered potential organ donors. Their mean age was 75.2 +/- 11 years. Sixty-eight (39%) were intubated, and 60 of these (34.5%) were mechanically ventilated. In addition, 94 patients (54%) died within 12 hours (median, 9.3 hours) after admission; and 13 (7%) died while receiving a maximum level of care. No diagnostic procedures were performed to assess brain death. CONCLUSION: A significant number of patients who die in emergency departments could be organ donors, including approximately 7% between 60 and 85 years of age with life threatening neurologic diseases. However, this percentage may be reduced by family opposition. Emergency physicians should collaborate with intensive care units and local organ donation teams to optimize end-of-life care and maximize the number of potential donors. PMID- 21035978 TI - Ink sick: tattoo ink hypersensitivity vasculitis. PMID- 21035979 TI - Bad Mojo: use of the new marijuana substitute leads to more and more ED visits for acute psychosis. PMID- 21035980 TI - High doses of warfarin are more beneficial than its low doses in patients with deep vein thrombosis. AB - BACKGROUND: The efficacy and safety of enoxaparin in outpatient treatment of deep vein thrombosis have been well studied. The present study aimed to compare the efficacy of a 10-mg loading dose of warfarin with 5 mg of the drug and enoxaparin in achieving the international normalized ratio (INR) range. METHODS: This randomized clinical trial was performed in the emergency department (ED) of our study. International normalized ratio was checked daily for 7 days and on the 14th day. Based on the patient's INR on the third day, the doses were adjusted. Patients received enoxaparin (1.5 mg/kg per day) simultaneously until the therapeutic range of INR was achieved for 2 consecutive days. RESULT: The side effects were compatible in both groups. There was a significant difference in the INR rates of the 2 groups recorded on the third, fourth, and seventh days. CONCLUSION: The 10-mg loading dose of warfarin induces the therapeutic range of INR earlier than the 5-mg dose without causing any significant difference in the side effects. More cases in the 10-mg group had INR levels higher than 3; the very dose, therefore, is recommended as the loading dose in cases of outpatients with deep vein thrombosis referring to the ED. Tight control of INR, after the third day of treatment, is also recommended in these cases. PMID- 21035981 TI - Temporal pattern of occurrence of cardiac emergencies. PMID- 21035982 TI - Predicting unfavorable outcome in subjects with diagnosis of chest pain of undifferentiated origin. AB - BACKGROUND: Subjects with chest pain and a negative diagnostic workup constitute a problem for emergency physicians. We tested the usefulness of clinical variables in predicting 30-day and 6-month outcome in subjects with chest pain of undifferentiated origin after a negative workup. METHODS: Chest pain of undifferentiated origin was diagnosed by negative first-line (serial electrocardiograms, troponins assays, and 12- to 24-hour observation) and second line evaluation (echocardiography, exercise tolerance test, stress scintigraphy, stress echocardiography, coronary angiography). Thirty-day and 6-month outcomes were considered unfavorable in the presence of any of the following: death, acute coronary syndrome, need for urgent coronary revascularization. The variables considered for risk stratification were age, sex, smoking, family history of coronary artery disease, presence of hypertension, high cholesterol levels, diabetes, chronic renal failure, cerebral vascular disease, and history of acute coronary syndrome, percutaneous transluminal angioplasty (PTA), coronary artery by pass graft, and heart failure. FINDINGS: Five items (diabetes, chronic renal failure, history of PTA or bypass, history of heart failure) were associated with 30-day unfavorable outcome (31 events/1262 cases; 2.5%). The receiver operating characteristic area of the selected items was 0.726 (95% confidence interval [CI], 0.654-0.798); sensitivity was 90.3% (73.1-95.8) and specificity was 54.8% (52.0-57.6). A similar panel of items (older age, diabetes, chronic renal failure, history of PTA) predicted an unfavorable 6-month outcome (90 subjects [7.1%], with lower accuracy (receiver operating characteristic area, 0.610 [95% CI, 0.594-0.627, P < .05]; sensitivity, 98.9% [95% CI, 93.1-99.6]; specificity, 21.6% [95% CI, 19.4-23.9]). INTERPRETATION: In subjects with chest pain of undifferentiated origin, the risk of unfavorable outcome cannot be accurately predicted by the selected clinical items. PMID- 21035983 TI - Diagnostic performance of a pocket-sized ultrasound device for quick-look cardiac imaging. AB - BACKGROUND: Although pocket-sized, simplified ultrasound devices have emerged to enable subjective point-of-care assessment, few data on their cardiac application exist. We sought to examine the image quality and the accuracy of subjective diagnosis of video loops obtained from a pocket-sized ultrasound device for 2 significant cardiac abnormalities, left ventricular systolic dysfunction and left atrial enlargement, obtained from a single, quick-look view. METHODS: Parasternal left ventricular long-axis images acquired with a miniaturized commercially available device (Acuson P10) were reviewed using subjective criteria for left ventricular systolic dysfunction and left atrial enlargement and were compared with M-mode measurements of left atrial systolic diameter and E-point septal separation from a fully featured echocardiograph in 78 inpatients referred for standard echocardiography. Interpretive confidence and image quality were evaluated with each interpretation. RESULTS: Of 78 inpatient studies, 19% of pocket ultrasound and 13% of standard studies were technically limited (P = NS). Of 61 technically adequate studies, subjective interpretation of pocket ultrasound images had a sensitivity, specificity, and accuracy of 79%, 52%, and 64% for left atrial diameter more than 4 cm; 47%, 98%, and 82% for E-point septal separation more than 1 cm of; 83%, 62%, and 74% for either abnormality; and 92%, 82%, and 87% for either abnormality when interpretive confidence was present (n = 23). The pocket ultrasound image quality scores were significantly lower than the standard echocardiograph (P < .001). CONCLUSION: The pocket-sized device provided adequate imaging for screening of 2 significant cardiac entities. Subjective interpretation of a single parasternal view may help identify patients with cardiac disease. PMID- 21035984 TI - Reduction of bowing forearm fractures in the ED under propofol sedation. AB - Bowing fractures of the long bones result from a deforming force that bends the bone similar to an archer's bow. In some of the earlier descriptions of bowing fractures, the recommended treatment for these was closed reduction under general anesthesia in the operating room. The aim of this study was to describe 2 pediatric patients with bowing fractures of the forearm that were successfully reduced in the emergency department (ED) under deep sedation with propofol. Two cases of bowing fractures of the forearm reduced in the ED under propofol sedation were described. Some bowing fractures of the forearm can be reduced in the ED under propofol sedation. PMID- 21035985 TI - Spinal epidural hematoma masquerading as atypical chest pain. PMID- 21035986 TI - Disseminated Lemierre syndrome presenting as septic arthritis. PMID- 21035987 TI - Falciform ligament sign after shock episode in an elderly man. PMID- 21035988 TI - Comparative effectiveness of the treatments for thoracic aortic transection [corrected]. AB - OBJECTIVES: To synthesize the available evidence regarding the outcomes associated with nonoperative management, open repair, and endovascular repair of thoracic aortic transection. METHODS: We searched electronic databases (MEDLINE, EMBASE Cochrane, Web of Science, and Scopus) for studies that enrolled patients with aortic transection and measured the outcomes of interest. Two reviewers determined study eligibility and extracted data. We estimated the event rate associated with the different approaches from case series and the relative risk from comparative studies. Estimates from each study were pooled using the random effects model. RESULTS: We found 139 studies that fulfilled the inclusion criteria, the majority of which were noncomparative surgical case series, retrospective, and none were randomized. Studies included 7768 patients, the majority of which were males. The mortality rate was significantly lower in patients who underwent endovascular repair, followed by open repair and nonoperative management (9%, 19%, and 46%, respectively, P < .01). No significant difference in event rate across the three groups was noted for the outcomes of anterior stroke, posterior stroke, or any stroke. The risk of spinal cord ischemia and end-stage renal disease were higher in open repair compared with the other 2 groups (9% vs 3% and 3%, P = .01 for spinal cord ischemia and 8% vs 5% and 3%, P = .01 for end-stage renal disease). Compared with endovascular repair, open repair was associated with an increased risk of graft infection and systemic infections. Meta-analyses of comparative studies demonstrated that compared with open repair, endovascular repair is associated with reduced mortality and spinal cord ischemia (relative risk, 0.61; 95% confidence interval, 0.46-0.80; and relative risk, 0.34; 95% confidence interval, 0.16-0.74; respectively). Inferences are limited by methodological quality, survival, and publication biases. CONCLUSIONS: Very low-quality evidence suggests that, compared with open repair or nonoperative management, endovascular repair of thoracic aortic transection is associated with better survival and decreased risk of spinal cord ischemia, renal injury, and graft and systemic infections. Nonoperative management is associated with the least favorable outcomes. PMID- 21035989 TI - Osteochondritis dissecans of the capitellum: a review of the literature and a distal ulnar portal. AB - Osteochondritis dissecans (OCD) of the humeral capitellum most commonly affects young athletes engaged in sports that repetitively stress the elbow. It is characterized by localized injury of subchondral bone of the humeral capitellum. To determine the best treatment option for OCD in young athletes, it is important to differentiate between stable and unstable OCD lesions. Stable lesions can be treated with rest, whereas unstable lesions, as well stable lesions that do not respond to conservative therapy, may require a surgical approach. Magnetic resonance imaging is the diagnostic study of choice to evaluate capitellar OCD lesions and loose bodies and to accurately determine the stability and viability of the OCD fragment. A variety of surgical approaches have been reported, from internal fixation of large fragments to autologous chondrocyte grafts. Arthroscopic surgery is becoming the standard treatment of capitellar OCD. This minimally invasive approach shows good results, a low risk of operative morbidity, and early recuperation postoperatively. The distal ulnar portal we describe here allows for ergonomic exposure to the posterolateral capitellum, providing easier access for drilling, burring, and local debridement of lesions amenable to arthroscopy. PMID- 21035990 TI - Transtibial versus anteromedial portal reaming in anterior cruciate ligament reconstruction: an anatomic and biomechanical evaluation of surgical technique. AB - PURPOSE: The purpose of this study was to objectively evaluate the anatomic and biomechanical outcomes of anterior cruciate ligament (ACL) reconstruction with transtibial versus anteromedial portal drilling of the femoral tunnel. METHODS: Ten human cadaveric knees (5 matched pairs) without ligament injury or pre existing arthritis underwent ACL reconstruction by either a transtibial or anteromedial portal technique. A medial arthrotomy was created in all cases before reconstruction to determine the center of the native ACL tibial and femoral footprints. A 10-mm tibial tunnel directed toward the center of the tibial footprint was prepared in an identical fashion, starting at the anterior border of the medial collateral ligament in all cases. For transtibial femoral socket preparation (n = 5), a guidewire was placed as close to the center of the femoral footprint as possible. With anteromedial portal reconstruction (n = 5), the guidewire was positioned centrally in the femoral footprint and the tunnel drilled through the medial portal in hyperflexion. An identical graft was fixed and tensioned, and knee stability was assessed with the following standardized examinations: (1) anterior drawer, (2) Lachman, (3) maximal internal rotation at 30 degrees , (4) manual pivot shift, and (5) instrumented pivot shift. Distance from the femoral guidewire to the center of the femoral footprint and dimensions of the tibial tunnel intra-articular aperture were measured for all specimens. Statistical analysis was completed with a repeated-measures analysis of variance and Tukey multiple comparisons test with P <= .05 defined as significant. RESULTS: The anteromedial portal ACL reconstruction controlled tibial translation significantly more than the transtibial reconstruction with anterior drawer, Lachman, and pivot-shift examinations of knee stability (P <= .05). Anteromedial portal ACL reconstruction restored the Lachman and anterior drawer examinations to those of the intact condition and constrained translation with the manual and instrumented pivot-shift examinations more than the native ACL (P <= .05). Despite optimal guidewire positioning, the transtibial technique resulted in a mean position 1.94 mm anterior and 3.26 mm superior to the center of the femoral footprint. The guidewire was positioned at the center of the femoral footprint through the anteromedial portal in all cases. The tibial tunnel intra-articular aperture was 38% larger in the anteroposterior dimension with the transtibial versus anteromedial portal technique (mean, 14.9 mm v 10.8 mm; P <= .05). CONCLUSIONS: The anteromedial portal drilling technique allows for accurate positioning of the femoral socket in the center of the native footprint, resulting in secondary improvement in time-zero control of tibial translation with Lachman and pivot-shift testing compared with conventional transtibial ACL reconstruction. This technique respects the native ACL anatomy but cannot restore it with a single-bundle ACL reconstruction. Eccentric, posterolateral positioning of the guidewire in the tibial tunnel with the transtibial technique results in iatrogenic re-reaming of the tibial tunnel and significant intra-articular aperture expansion. CLINICAL RELEVANCE: Anteromedial portal drilling of the femoral socket may allow for improved restoration of anatomy and stability with ACL reconstruction compared with conventional transtibial drilling techniques. PMID- 21035991 TI - Medial meniscus root tear refixation: comparison of clinical, radiologic, and arthroscopic findings with medial meniscectomy. AB - PURPOSE: To investigate the clinical, radiologic, and arthroscopic findings of pullout repair in medial meniscus root tear (MRT) and to compare the results of pullout repair and partial meniscectomy. METHODS: This study enrolled 58 consecutive patients with medial MRT who underwent partial meniscectomy (M group, n = 28) or pullout repair (R group, n = 30) between September 2003 and August 2007. The patients were evaluated by the Lysholm knee score, International Knee Documentation Committee (IKDC) subjective knee score, joint space narrowing, and Kellgren-Lawrence grade on simple radiographs. Medial meniscal extrusion and the state of the meniscus and articular cartilage on magnetic resonance imaging (MRI) were documented. We performed second-look arthroscopy in 14 patients with pullout repair and evaluated fixation strength and hoop tension of the meniscus and the state of the articular cartilage. RESULTS: There were no differences in demographic data (age, sex, and body mass index) between the 2 groups. The mean follow-up was 48.5 months in the R group and 46.1 in the M group. Lysholm and IKDC scores improved significantly in both groups (P < .05). However, the R group had better Lysholm and IKDC scores and less joint space narrowing and progression of the Kellgren-Lawrence grade than the M group did (P < .05). In a subgroup analysis of the R group, medial meniscal extrusion on MRI decreased from 3.13 to 2.94 mm. Of the patients, 28 (93.3%) showed complete or partial healing of the meniscus. On MRI, 6 (20%) showed arthrosis progression. On second-look arthroscopic examinations in 14 patients in the R group, 9 (64.3%) showed normal fixation strength, 10 (71.4%) had normal restoration of hoop tension, 5 (35.7%) showed arthrosis progression, and 2 (6.7%) had repeat tears of the meniscus. CONCLUSIONS: Arthroscopic pullout repair of a medial MRT gave significantly better clinical and radiologic results than partial meniscectomy, and sound healing with restoration of hoop tension of the meniscus was observed on MRI and second-look arthroscopy. We propose that this method is an effective treatment for medial MRT. LEVEL OF EVIDENCE: Level III, retrospective comparative study. PMID- 21035992 TI - A comparison of forearm supination and elbow flexion strength in patients with long head of the biceps tenotomy or tenodesis. AB - PURPOSE: The purpose of this study was to compare the forearm supination and elbow flexion strength of the upper extremity in patients who have had an arthroscopic long head of the biceps tendon (LHBT) release with patients who have had an LHBT tenodesis. METHODS: Cybex isokinetic strength testing (Cybex Division of Lumex, Ronkonkoma, NY) was performed on 17 patients who underwent arthroscopic LHBT tenotomy, 19 patients who underwent arthroscopic LHBT tenodesis, and 31 age , gender-, and body mass index-matched control subjects. Subjects were considered fully recovered from shoulder surgery, were released for unrestricted activities, and were at least 6 months after surgery before testing. Subjects were tested for forearm supination and elbow flexion strength of both arms by use of a Cybex II NORM isokinetic dynamometer at 60 degrees /s and 120 degrees /s. Testing was performed on injured and uninjured arms as well as dominant and nondominant arms in control subjects. Both forearm supination and elbow flexion strength values were recorded. RESULTS: Comparison between the involved and uninvolved upper extremities within each group by use of a paired t test showed a 7% increase in elbow flexion strength when the dominant and nondominant arms were compared at 60 degrees /s. Neither the tenotomy nor tenodesis groups exhibited elbow flexion strength differences at 120 degrees /s (all P >= .147). Comparison between groups by use of 2 * 3 analysis of variance (speed * group) showed no statistical difference in either forearm supination or elbow flexion strength when we compared the tenotomy, tenodesis, and control groups. CONCLUSIONS: In asymptomatic patients who have had biceps tenotomy or tenodesis, no statistically significant forearm supination or elbow flexion strength differences existed in the involved extremity between the 2 study groups. LEVEL OF EVIDENCE: Level III, case-control study. PMID- 21035993 TI - Static and dynamic mechanical causes of hip pain. AB - Mechanical hip pain typically has been associated either with dynamic factors resulting in abnormal stress and contact between the femoral head and acetabular rim when the hip is in motion or with static overload stresses related to insufficient congruency between the head and acetabular socket in the axially loaded (standing) position. Compensatory motion may adversely affect the dynamic muscle forces in the pelvic region, leading to further strain and pain. Hip pain related to static overload stresses may also be localized to the anteromedial groin, but compensatory dysfunction of the periarticular musculature may lead to muscular fatigue and associated pain throughout the hip. As our understanding of hip joint mechanics has advanced, it has become increasingly apparent that hip pain in the absence of osteoarthritis may be due to a complex combination of mechanical stresses, both dynamic and static. With an emphasis on findings in the recent literature, this review will describe the dynamic and static factors associated with mechanical hip pain, the combinations of dynamic and static stresses that are commonly identified in hip pain, and common patterns of compensatory injury in patients with femoroacetabular impingement. PMID- 21035994 TI - Patient-reported outcome instruments for femoroacetabular impingement and hip labral pathology: a systematic review of the clinimetric evidence. AB - PURPOSE: The purpose of this study is to systematically review the content and clinimetric evidence (rigor of rating scales and indexes for the description of clinical phenomena) of published patient-reported outcome (PRO) instruments used to assess femoroacetabular impingement (FAI) and labral hip pathology. METHODS: We used Medical Subject Heading terms related to FAI and labrum/labral tears to search the Medline, Embase, and Cochrane databases for studies of FAI and labral hip pathology. Studies with hip-related PRO instruments, with any operative intervention except total hip arthroplasty, were included. We excluded studies with a skeletally immature population, revision surgeries in more than 10% of cases, or a primary diagnosis of hip osteoarthritis. We conducted a second review using the same databases for studies reporting clinimetric properties of at least 1 of the PRO instruments identified previously. Articles were selected in an independent, stepwise manner by 2 reviewers. Selected articles were evaluated to determine the presence and quality of measurement properties of the outcome instruments. RESULTS: We found 5 articles assessing 3 PRO instruments: the Hip Outcome Score (HOS), the Non-Arthritic Hip Score, and the 12-item modified Western Ontario and McMaster Universities Osteoarthritis Index. The HOS had the highest positive rating for internal consistency, construct validity, agreement, responsiveness, lack of floor/ceiling effect, and interpretability. The Non Arthritic Hip Score showed evidence for validity and lack of floor/ceiling effect. The modified Western Ontario and McMaster Universities Osteoarthritis Index was only strong for internal consistency and was indeterminate for construct validity. CONCLUSIONS: Only 3 PRO instruments have shown clinimetric evidence to support their use to measure outcomes in FAI and labral pathology patients. The HOS has the greatest amount of clinimetric evidence and is the most proven instrument for use in this population. This review shows that further clinimetric evaluation of commonly used PRO instruments for nonarthritic hip pathology is warranted. PMID- 21035995 TI - Evaluation of bone bruises and associated cartilage in anterior cruciate ligament injured and -reconstructed knees using quantitative t(1rho) magnetic resonance imaging: 1-year cohort study. AB - PURPOSE: To quantitate bone marrow edema-like lesions (BMELs) and the radiologic properties of cartilage in knees with acute anterior cruciate ligament (ACL) injuries using T(1rho) magnetic resonance imaging over a 1-year period. METHODS: Nine patients with ACL injuries were studied. Magnetic resonance imaging scans were acquired within 8 weeks of the injury, after which ACL reconstruction surgery was performed. Images were then acquired 0.5, 6, and 12 months after reconstructions. The volume and signal intensity of BMELs were quantified at baseline and follow-up examinations. T(1rho) values were quantified in cartilage overlying the BMEL (OC) and compared with surrounding cartilage at all time points. RESULTS: BMELs were most commonly found in the lateral tibia and lateral femoral condyle. Nearly 50% of BMELs resolved over a 1-year period. The T(1rho) values of the OC in the lateral tibia, medial tibia, and medial femoral condyle were elevated compared with respective regions in surrounding cartilage at all time points; the difference was significant only in the lateral tibia (P < .05). The opposite results were found in the lateral femoral condyle. For the medial tibia and medial femoral condyle, none of the time periods was significantly different. The percent increase in T(1rho) values of OC in the lateral tibia was significantly correlated with BMEL volume (r = 0.74, P < .05). At 1 year, the OC in the lateral tibia, medial tibia, and medial femoral condyle showed increased T(1rho) values despite improvement of BMEL. CONCLUSIONS: In patients after ACL tear and reconstruction, (1) the cartilage overlying BMEL in the lateral tibia experiences persistent T(1rho) signal changes immediately after acute injuries and at 1-year follow-up despite BMEL improvement, (2) the superficial layers of the overlying cartilage show greater matrix damage than the deep layers, and (3) the volume of the BMEL may predict the severity of the overlying matrix's damage in the lateral tibia. T(1rho) is capable of quantitatively and noninvasively monitoring this damage and detecting early cartilage changes in the lateral tibia over time. LEVEL OF EVIDENCE: Level IV, therapeutic case series. PMID- 21035996 TI - [Lemierre's syndrome]. AB - Lemierre's syndrome is a rare disease, mostly affecting young adults in good health, which can lead to significant morbidity and mortality. We report one case with favourable outcome and clinical features stereotypics: angina, septic thrombosis of the internal jugular vein, pulmonary septic metastasis, Fusobacterium necrophorum on blood cultures. Antibiotic therapy targeting anaerobes has been rapidly initiated and maintained 4-6 weeks. The anticoagulation has been maintained 4 weeks. PMID- 21035997 TI - [Obstetrical epidural analgesia during labour: one dural puncture, repeated postural headaches, three blood patches...]. AB - We report the case of a patient in whom three blood patches had to be performed to treat a post-dural puncture headache following the insertion of an epidural catheter for labour analgesia. There are few data about repeated blood patches used to treat recurring symptoms after failure of a previous blood patch. The technical guidelines used to perform a first blood patch should be followed for the next procedure as well. The role of the cerebrospinal fluid leaking in the symptoms has to be verified, to avoid performing a useless blood patch and to miss another cause, which needs an urgent treatment. PMID- 21035998 TI - [Wrong side iliofascial block in a patient with hip fracture]. AB - We report the case of a patient who received a wrong side iliofascial block immediately before being operated for a femoral neck fracture. This error did not lead to any adverse consequence but this case confirms that wrong side or wrong site error can also occur in anaesthetic practice, especially in emergency procedures, and is not only confined to surgical practice. Anaesthesiologists should be careful when performing unilateral procedures and implement similar strategies than those used by surgeons. PMID- 21035999 TI - [Ehlers-Danlos syndrome type II discovered during caesarean: what to do?]. PMID- 21036000 TI - [Pulmonary embolism following medical decompression of abdominal compartment syndrome]. PMID- 21036001 TI - [Delayed circulatory failure after meprobamate poisoning in a patient carrying a gastric band]. PMID- 21036002 TI - [Ovarian immature teratoma during pregnancy]. PMID- 21036003 TI - Bleeding peptic ulcers resistant to endoscopic treatment: calling for a surgeon or an interventional radiologist? PMID- 21036004 TI - [Half of the patients with primary hyperparathyroidisms have a vitamin D deficiency: aggravating the osseous attack]. AB - BACKGROUND: Primary hyperparathyroidism (PHPT) associates hypocalcemia and hypophosphatemia secondary to parathyroid hormone (PTH) excess. PHPT is asymptomatic for 80% of patients and responsible for a decrease in bone mineral density particularly in women. Vitamin D deficiency increases the risk of bone fractures. METHODS: We performed a prospective analysis of patients with PHPT in order to evaluate the prevalence of vitamin D deficiency. We determined the effects of vitamin D deficiency on bone metabolism: calcium, phosphate and PTH levels. We also analyzed biochemical markers of bone remodeling and bone mineral density (BMD) before and 6 months after vitamin D replacement. RESULTS: 75 patients with PHPT were identified: 38 patients with vitamin D deficiency but only 22 patients could be followed (G1). 14 patients with a normal level of vitamin D were followed (G2). Prevalence of vitamin D deficiency was 51%. Calcium and phosphate levels were similar into both groups. PTH levels were higher in the G1 group. Calciuria was significantly lower in the G1. For markers of bone formation (fragments of collagen CTX and alkaline phosphatase): osteocalcine levels were higher in G1 group. For bone resorption: telopeptides levels were significantly higher in the G1 group. T score was significantly lower in this group, favoring a significant osseous attack. After 6 months of substitution with vitamin D, calcium decreased and hypophosphatemia normalized. PTH levels decreased (-50.7%). Calciuria increased without risks of urinary lithiasis. Bone mineral density loss decreased while markers of bone turn over increased. DISCUSSION: Vitamin D deficiency increases the risk of bone fragility in PHPT. Few data are available in France concerning the prevalence of vitamin D deficiency in PHPT. Our results were similar to data in other countries. Vitamin D replacement with regular monitoring of calcium and calciuria levels is beneficial for metabolic and hormonal status, improves bone density, without systematic opposing effects. The follow-up of effectiveness by BMD could be associated with measurement of markers of bone remodeling. CONCLUSION: In asymptomatic PHPT, particularly those for which surgery is not indicated, measurement of 25 OH Vitamin D should be systematic. It is recommended before surgery. PMID- 21036005 TI - Precocious hypothyroidism mechanisms after radioiodine treatment in Graves' disease. AB - OBJECTIVE: Hypothyroidism can occur after radioiodine treatment for Graves' disease. It may happen precociously and transiently in the first year after treatment. The purpose of this study was to understand the mechanisms responsible for precocious hypothyroidism. METHODS: 36 patients treated for Graves disease by radiodiodine were prospectively studied; The following variables were included in the analysis: age, gender, attendance for Graves' orbitopathy (GO), delay before radioiodine treatment, number of recurrences, previous treatments, corticosteroid therapy, thyroid mass, and (131)I dose. The titres of free T4 (FT4), thyroid stimulating hormone (TSH), anti-TSH receptor antibodies (TRAb), anti-thyroid peroxydase antibodies (TPOAb) and anti-thyroglobulin antibodies (TGAb) were monitored. Thyroid stimulating (TSAb) and blocking (TBAb) antibodies were determined and (123)I uptake was measured when hypothyroidism occurred. RESULTS: 23 patients became precociously hypothyroid (group A) while 13 patients did not (group B). The initial TGAb titre was higher in group A (p=0.0024), and corticosteroid therapy was used more frequently to avoid aggravating GO in group B (p=0.0276). TPOAb and TGAb titres increased significantly only in group A (p=0.0112 and p=0.0202, respectively). When hypothyroidism occurred, TBAb was present in 13 patients. Transient hypothyroidism due to TBAb was observed in 1 patient. No iodide organification impairment was disclosed by the perchlorate test. CONCLUSION: Radioinduced thyroiditis appears to be the main mechanism involved in the pathogenesis of precocious hypothyroidism. A higher TGAb titre before treatment is associated with precocious hypothyroidism, suggesting the prognostic value of TGAb. Transient hypothyroidism directly due to TBAb remains rare. PMID- 21036006 TI - Navigation-assisted minimal invasive total knee arthroplasty in patients with extra-articular femoral deformity. PMID- 21036007 TI - Dislocation of large diameter metal-on-metal bearings an indicator of metal reaction? AB - We report 3 patients who underwent total hip arthroplasty (THA) using large diameter metal-on-metal bearing. These patients initially presented with pain but went on to develop dislocation of the THA while awaiting investigations. Any pain following metal-on-metal bearing THA should be taken seriously and should trigger investigations to identify a metal reaction. If left untreated, these reactions can cause progressive soft tissue necrosis leading to instability. These patients should be considered for early revision of the bearing surface to prevent further soft tissue damage. PMID- 21036008 TI - The value of magnetic resonance imaging in investigating a painful total knee arthroplasty. AB - This case describes a rare cause of pain around a total knee arthroplasty and highlights the importance of a structured approach to the investigation of these patients. Magnetic resonance imaging provided detailed information about the cause of pain despite the presence of a prosthetic joint, and the pathology, primary non-Hodgkin lymphoma, was treated without the need for further surgical intervention. PMID- 21036009 TI - Midterm results of a porous tantalum monoblock tibia component clinical and radiographic results of 108 knees. AB - The use of Trabecular Metal (TM), a biomaterial manufactured from elemental tantalum metal, has recently increased in orthopedics. One hundred eight consecutive TM monoblock tibias were implanted in 95 patients and followed for a minimum of 2 years. The average follow-up was 4.5 years. The average age was 65 years. The Knee Society score of 36 improved to 89. One hundred five of the knees were rated good/excellent, and 3 knees were rated poor. Two patellar revisions were performed for loose components and one for patellar misalignment. One patella fracture required open reduction and internal fixation. One femur was revised. There were no tibia revisions. There were no progressive radiographic lucencies. Midterm clinical and radiographic results of 108 consecutive TM tibia components have a high rate of success. PMID- 21036010 TI - Component alignment after minimally invasive total knee arthroplasty: results of the first 100 cases performed. AB - It has been suggested that minimally invasive total knee arthroplasties increase the risk of component malalignment. Results during the period of initial learning curve on component malalignment are relatively unknown but should be addressed. This study reports the component alignment data of the first 100 minimally invasive total knee arthroplasties performed by a single surgeon from the very start of a community-based practice immediately after fellowship training. The results indicate that the initial learning curve produces results comparable to reported results of standard total knee arthroplasties. PMID- 21036011 TI - Knee kinematics of high-flexion activities of daily living performed by male Muslims in the Middle East. AB - Full flexion is critical for total knee arthroplasty (TKA) patients in the Middle East, where daily activities require a high range of motion in the lower limb. This study aimed to increase understanding of the knee kinematics of normal Muslim subjects during high-flexion activities of daily living, such as kneeling, Muslim prayer, sitting cross-legged, and squatting. The early postoperative kinematics for a select group of Muslim, high-flexion TKA patients are also reported. Mean curves were compared between the normal group and the TKA group. During kneeling, the average maximum flexion was 141.6 degrees for the normal group and 140.2 degrees for the TKA group. The normal group's maximum and minimum knee angles (flexion, abduction, external rotation) were reported and, with the exception of maximum extension, were not significantly different from the TKA group, despite short postoperative times. PMID- 21036012 TI - Early range of motion of the scorpio non-restrictive geometry cruciate-retaining total knee system. AB - Flexion following total knee arthroplasty in the US population generally falls between 100 degrees and 120 degrees . Because of these relatively low flexion arcs, total knee arthroplasty prosthetic designs emerged allowing "high flexion" (>=125 degrees ). We hypothesized that a high-flexion implant design, Scorpio Non Restrictive Geometry cruciate-retaining knee prosthesis, would allow clinical early maximum flexion of at least 125 degrees . A prospective observational cohort study enrolled 87 unselected patients (94 knees) evaluated preoperation and 3 months and 1 year postoperation for clinical flexion, arc of motion, and Knee Society scores. At 1 year, 67% of knees had improved flexion and 23% achieved flexion of at least 125 degrees . Clinically, flexion improved by 6.9 degrees and total arc of motion improved by 10.6 degrees from preoperation to 1 year postoperation. Although this high-flexion design allows increased flexion, many patients fail to achieve flexion of at least 125 degrees . PMID- 21036013 TI - A review of defining and measuring sociability in children with intellectual disabilities. AB - There is a substantial body of research indicating that compromised social functioning for individuals with intellectual disabilities has far reaching implications for quality of life, community participation and wellbeing. However, an inherent difficulty for research into social functioning is the lack of agreed definition of key concepts in the area. The current paper reviews definitions for four concepts related to the central concept of sociability (social cognition, social competence, social skills and social behaviour). By reviewing the definitions available in the wider social and cognitive psychology literature and comparing these to definitions provided in research with individuals with intellectual disabilities it is clear that concepts are poorly defined. The current article proposes working definitions which may be used give impetus to future debate in the area. The clinical implications of having implicitly understood concepts rather than definable and measurable traits are considered. The review calls for researchers to provide definitions for the concepts under investigation and their relationship to measures employed in research. PMID- 21036014 TI - Presurgical language fMRI activation correlates with postsurgical verbal memory decline in left-sided temporal lobe epilepsy. AB - We analysed the association of presurgical language fMRI activations and postsurgical verbal memory changes in 16 left-sided mesial temporal lobe epilepsy patients with initially intact memory. Patients with severe verbal memory decline after surgery (n = 9) had stronger presurgical fMRI activations within the left posterior temporal lobe, compared to those with no decline (n = 7). Language fMRI activation may predict verbal memory outcome, even in patients with a high risk of postsurgical memory deterioration. PMID- 21036016 TI - Age-related cortical thinning in schizophrenia. AB - Although the effects of aging on the neural correlates of schizophrenia have been researched for many years, no clear conclusion has been reached. While some studies have demonstrated progressive age-related gray matter reductions in schizophrenia, other studies have not found evidence of progression. Moreover, it remains unclear whether the influence of aging on global or regional cortical thickness differs between schizophrenia patients and healthy controls. This study aimed to confirm previous reports of reduced cortical thickness in schizophrenia, and to investigate the effects of age on global and regional cortical thickness. Eighty-three patients with schizophrenia (six first-episode patients and 77 chronic patients; age range=18-55 years) and 90 age-, gender- and education matched healthy controls (age range=19-56 years) underwent structural magnetic resonance imaging (MRI) using a 3-Tesla scanner. Surface-based analysis was applied to assess cortical thickness in the whole brain. The patient group exhibited both global and regional cortical thinning in regions including the prefrontal and temporal cortices. The correlation between age and cortical thickness showed a similar pattern in patients and controls, both globally and regionally. These results suggest that the reduction of cortical thickness in schizophrenia might not be progressive over the course of the illness, indicating that pathological processes occur in a relatively limited period of time around the onset of illness. PMID- 21036015 TI - PAOPA, a potent analogue of Pro-Leu-glycinamide and allosteric modulator of the dopamine D2 receptor, prevents NMDA receptor antagonist (MK-801)-induced deficits in social interaction in the rat: implications for the treatment of negative symptoms in schizophrenia. AB - The aim of this study was to investigate whether a potent analogue of the endogenous brain peptide l-prolyl-l-leucyl-glycinamide (PLG), (3(R)-[(2(S) pyrrolidinylcarbonyl)amino]-2-oxo-1-pyrrolidineacetamide (PAOPA), can prevent the induction of social withdrawal caused by sub-chronic treatment with the non competitive NMDA (N-methyl-l-aspartate) receptor antagonist, MK-801. Results indicate that MK-801 (0.5 mg/kg) significantly decreased social interaction following sub-chronic treatment (7 days). Treatment with PAOPA (1 mg/kg) blocked the effects of MK-801, and increased the amount of time spent in social interaction in comparison to control animals. These results provide evidence for the development of peptidomimetic compounds for the treatment of social withdrawal and related negative symptoms associated with schizophrenia. PMID- 21036017 TI - In vivo proton magnetic resonance spectroscopic examination of benzodiazepine action in humans. AB - In an examination of the effect of benzodiazepines on brain chemistry, 44 healthy controls underwent a short echo-time proton magnetic resonance spectroscopy ((1)H MRS) session after induced sedation with intravenous midazolam (0.03mg/kg) plus fentanyl (2MUg/kg). The regions of interest were the anterior cingulate cortex, right basal ganglia, right frontal lobe, and right hippocampus. Twenty-five of these subjects underwent the second (1)H MRS session while awake. The measured (1)H MRS metabolites included N-acetyl-aspartate, creatine-containing compounds (PCr+Cr), choline-containing compounds, myo-inositol, and glutamate plus glutamine, which were quantified both as absolute values and metabolite/PCr+Cr ratios. The results were analyzed using independent group t tests and repeated measures analysis of variance (ANOVA, with alpha values set at 0.025 to minimize the risk of false-positive findings arising from multiple comparisons. No significant difference between subjects under midazolam plus fentanyl induced sedation and awake could be detected with unpaired analyses. Paired comparisons by ANOVA with repeated measures found that neither drug (midazolam plus fentanyl) nor the drug by time (interval between two scan times) interaction had a significant effect on the quantified metabolites. These findings encourage utilization of benzodiazepine-induced brief sedation during in vivo (1)H MRS experiments of the brain, and may help with elucidation of state-dependent neurochemical alterations during the course of bipolar and schizoaffective disorders. PMID- 21036018 TI - Time-dependent adsorption behavior of beta-lactoglobulin on ZnSe crystal surface studied by 2D correlation ATR/FTIR spectroscopy. AB - The time-dependent adsorption behavior of beta-Lactoglobulin (beta-Lg) on ATR crystal (ZnSe) surface was studied by two-dimensional (2D) correlation ATR/FTIR spectroscopy. More bands were resolved by 2D correlation spectroscopy compared to the results from second derivative (SD) and Fourier self-deconvolution (FSD) analyses, but some of the new bands resolved may originate from bandwidth changes, wavenumber shifts, etc. The integrated/overall sequential order of the intensity changes of the four sub-bands in amide I region obtained from 2D correlation spectroscopy was not consistent with the experimental observation. Adsorption-induced conformational changes did not occur until 10 min of adsorption of beta-Lg molecules on the ZnSe crystal surface. The relative contents of the low-wavenumber component of the antiparallel beta-strands (1627cm(-1)) and random segments with alpha-helix (1651cm(-1)) changed prior to beta-turns (1666cm(-1)) and the high-wavenumber component of the antiparallel beta-strands (1684cm(-1)). More specifically, from about 10 to 15min of adsorption, the loss content of the low-wavenumber component of the antiparallel beta-strands (1627cm(-1)) was simultaneously transformed into random segments (1651cm(-1)). After 20 min of adsorption, the content of beta-turns (1666cm(-1)) started to decrease, and the loss of beta-turns (1666cm(-1)) was also transformed into antiparallel beta-strands (high-wavenumber component at 1684cm(-1)) in a cooperative way as the beta-Lg molecules become more extended. PMID- 21036019 TI - Effects of captopril on the cysteamine-induced duodenal ulcer in the rat. AB - Oxidative stress is important factor underlying in a variety of diseases. Antioxidative enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) are part of the physiological defenses against oxidative stress. Malondialdehyde (MDA) is a lipid peroxidation biomarker and its elevated level in various diseases is related to free radical damage. Cysteamine is a cytotoxic agent, acting through generation of reactive oxygen species (ROS) and may decrease defense activity of antioxidative enzymes against ROS and induce duodenal ulcer. Captopril, acts as free radical scavengers and protect against injuries from oxidative damage to tissues.The aim of this study was the evaluation of the effect of captopril against cysteamine-induced duodenal ulcer by determining duodenal damage, duodenal tissue SOD and GSH-PX activities and plasma MAD level. This study was performed on 3 groups of 7 rats each: saline, cysteamine and cysteamine plus captopril treated groups. The effect of captopril against cysteamine-induced duodenal ulcer is determined by evaluating the duodenal damage, duodenal tissue SOD and GSH-PX activities and plasma MDA level. All animals were euthanized 24h after the last treatment and 2 ml blood and duodena samples were collected for calculation of ulcer index, histopathological assessment and measurement of tissue SOD, GSH-PX activities and plasma MDA level. Cysteamine produced severe duodenal damage, decreased the activity of duodenal tissue SOD and GSH-PX and increased the plasma MDA level compared with saline pretreated rats. Pretreatment with captopril decreased the cysteamine-induced duodenal damage and plasma level of MDA and increased the activities of SOD and GSH-PX in duodenal tissue compared with cysteamine pretreated animal. Our results suggest that captopril protects against cysteamine-induced duodenal ulcer and inhibits the decrease in SOD and GSH-PX activities and lipid peroxidation by increasing antioxidant defenses. PMID- 21036020 TI - Between-population differences in digestive flexibility in the olivaceous field mouse. AB - The flexibility of digestive traits characterizes a standard model of physiological flexibility, demonstrating that animals adjust their digestive attributes in order to maximize overall energy return. Using an intraspecific experimental study, we evaluated the amount of flexibility in digestive tract mass and length in individuals from field mouse populations inhabiting semi-arid and temperate rain forest habitats and acclimated for six months to diets of different qualities. In accordance with the predictions of the theory of digestion, we observed a highly significant relationship between dietary variability and digestive flexibility in both specific digestive chambers and in the total digestive tract mass and length. Specifically, we found higher digestive plasticity in response to diet quality in rodents inhabiting southern temperate ecosystems with higher dietary variability in comparison to individuals from northern semi-arid habitats. PMID- 21036021 TI - Ontogenetic shifts in functional morphology of dragonfly legs (Odonata: Anisoptera). AB - Anisopteran leg functions change dramatically from the final larval stadium to the adult. Larvae use legs mainly for locomotion, walking, climbing, clinging, or burrowing. Adults use them for foraging and grasping mates, for perching, clinging to the vegetation, and for repelling rivals. In order to estimate the ontogenetic shift in the leg construction from the larva to the adult, this study quantitatively compared lengths of fore, mid, and hind legs and the relationships between three leg segments, femur, tibia, and tarsus, in larval and adult Anisoptera of the families Gomphidae, Aeshnidae, Cordulegastridae, Corduliidae, and Libellulidae, represented by two species each. We found that leg segment length ratio as well as ontogenetic shift in length ratios was different between families, but rather similar within the families. While little ontogenetic shift occurred in Aeshnidae, there were some modifications in Corduliidae and Libellulidae. The severest shift occurred in Gomphidae and Cordulegastridae, both having burrowing larvae. These two families form a cluster, which is in contrast to their taxonomic relationship within the Anisoptera. Cluster analysis implies that the function of larval legs is primarily responsible for grouping, whereas adult behavior or the taxonomic relationships do not explain the grouping. This result supports the previous hypothesis about the convergent functional shift of leg characters in the dragonfly ontogenesis. PMID- 21036022 TI - In vivo anti-tumour activity of corilagin on Hep3B hepatocellular carcinoma. AB - We have investigated the potential in vivo anti-tumour activity of corilagin using the Hep3B hepatocellular carcinoma cell line and an athymic nude mice xenograft model. The purity of corilagin was confirmed by high performance liquid chromatographic analysis. Corilagin was administrated intraperitoneally for a continuous period of 7 days at a concentration of 15 mg/kg of body weight per day. A significant inhibition of tumour growth was observed when treated mice are compared with control groups. Furthermore, analysis of enzymes markers of liver function, including alanine aminotransferase and asparate aminotransferase, suggested that current therapeutic dosage of corilagin did not exert adverse effect on liver. Our observations support the view that corilagin is considerably effective to retard the in vivo growth of xenografted Hep3B hepatocellular carcinoma. PMID- 21036023 TI - Ganoderic acid Mf and S induce mitochondria mediated apoptosis in human cervical carcinoma HeLa cells. AB - In this work, the effects of a pair of positional isomer of ganoderic acids (GAs), namely ganoderic acid Mf (GA-Mf) and ganoderic acid S (GA-S) purified from the fermented mycelia of Ganoderma lucidum, on induction of cell apoptosis and the apoptotic pathway in HeLa cells were investigated. The results demonstrate that both isomers decreased cell population growth on various human carcinoma cell lines by MTT assay, while GA-Mf had better selectivity between normal and cancer cells. The flow cytometry analysis indicated that treatment of HeLa cells with GA-S caused cell cycle arrest in the S phase, while GA-Mf caused cell cycle arrest in the G1 phase. Compared with GA-S, GA-Mf had more potent increase in the number of early and late apoptotic cells. Treatment of HeLa cells with each isomer decreased the mitochondria membrane potential and caused the release of cytochrome c from mitochondria into the cytosol. In addition, stimulation of caspase-3 and caspase-9 activity was observed. The Bax/Bcl-2 ratio was also increased in GA-treated HeLa cells. The results demonstrated that both isomers GA Mf and GA-S induced apoptosis of human HeLa cells through a mitochondria mediated pathway, but they had the different cell cycle arrest specificity. The findings will be helpful to the development of useful cancer chemopreventive compounds from G. lucidum. PMID- 21036024 TI - Cost-saving effect of supervised exercise associated to COPD self-management education program. AB - BACKGROUND: Although the benefits of comprehensive pulmonary rehabilitation have been demonstrated in patients with COPD, the effects of exercise sessions within self-management programs remain unclear. We hypothesized that 8 supervised exercise sessions incorporated in a 1-month self-management education program in COPD patients would be effective to improve health outcomes and to reduce direct medical costs after one year, compared to usual care. METHODS: In this randomized controlled trial, 38 moderate-to-severe COPD patients were assigned either to an intervention group or to a usual care group. The hospital-based intervention program provided a combination of 8 sessions of supervised exercise with 8 self management education sessions over a 1-month period. The primary end-point was the 6-min walking distance (6MWD), with secondary outcomes being health-related quality of life (HRQoL)--using the St. George's Respiratory Questionnaire (SGRQ) and Nottingham Health Profile (NHP), maximal exercise capacity and healthcare utilization. Data were collected before and one year after the program. RESULTS: After 12 months, we found statistically significant between-group differences in favor of the intervention group in 6MWD (+50.5 m (95%CI, 2 to 99), in two domains of NHP (energy, -19.8 (-38 to -1); emotional reaction, -10.4 (-20 to 0)); in SGRQ symptoms (-14.0 (-23 to -5)), and in cost of COPD medication (-480.7 ? (CI, -891 to -70) per patient per year). CONCLUSION: The present hospital-based intervention combining supervised exercise with self-management education provides significant improvements in patient's exercise tolerance and HRQoL, and significant decrease of COPD medication costs, compared to usual care. PMID- 21036025 TI - "We don't have no drugs education": The myth of universal drugs education in English secondary schools? AB - BACKGROUND: Despite concerns regarding youth drug use and 'standards' of drugs education in British schools, little is known about young people's routine experiences of drugs education at school, or schools' other priorities, policies and practices relating to drugs. METHODS: Qualitative data were collected through semi-structured interviews with students aged 14-15 (N=50) and teachers (N=10) at four schools in England. We used thematic content analysis to explore: young people's accounts of drugs education at secondary school and what they have learnt from this; and students' and teachers' accounts of schools' wider policies and practices relating to drugs. RESULTS: A recurring theme was that students reported having received little or no drugs education; the majority could not remember having had any at their secondary school. These students were not the 'drugwise' youth described in the normalisation thesis and young people wanted their school to provide them with more information. Teachers recognised that schools' drugs policies were rarely implemented in practice and that drugs education was not a priority. Schools also appear to be adopting new strategies based on surveillance and targeting to control students' drug use. In some cases referrals to a drugs counsellor were coercive and appeared to merely replace classroom-based drugs education. CONCLUSION: This study provides further evidence of the gap between drug policies and practice. It may be possible to increase the priority given to comprehensive drugs education and supportive drugs policies by modifying the incentive structures that schools work within. New targeted responses are unlikely to be effective at reducing drug-related harm at a population level because of the small number of students reached, and can be stigmatising. Further research is needed to explore schools' focus on surveillance and targeted control rather than universal education, and to examine interventions that might ensure schools implement adequate drugs education. PMID- 21036026 TI - Scrutinizing compost properties and their impact on methane oxidation efficiency. AB - Methane emissions from active or closed landfills can be reduced by means of microbial methane oxidation enhanced by properly designed landfill covers and engineered biocovers. Composts produced using different waste materials have already been proven to support methane oxidation, and may represent a low-cost alternative to other suitable substrates such as sandy or humic-rich soils, which are frequently not available in sufficient amounts or are too costly. In the present study a data set of 30 different compost materials (different age and input materials) and mixtures, as well as seven soils and mineral substrates were tested to assess methane oxidation rate under similar conditions in a laboratory column set-up. Multivariate data analysis (discriminant analysis) was applied to predict the influence of 21 different parameters (chemical, maturation and physical) on methane oxidation rate in a PLS-DA model. The results show that bulk density, total nutrient content (nitrogen and phosphorus), as well as the quantity and quality (with respect to maturity) of organic matter determined methane oxidation rate in this data set. The model explained 50% of the data variation, indicating how characterisation of oxidation rate by single, even diverse conventional parameters was limited. Thus for the first time, Fourier Transform Infrared (FTIR) spectroscopy was applied to a series of samples to better determine the characteristics of methane-oxidising materials. The initial data obtained in this study appear to be most promising. The prediction of specific methane oxidation rate of a potential biocover material from FTIR spectra and multivariate data analyses is a target to be focused on in the future. PMID- 21036027 TI - Dielectric properties of glucose in bulk aqueous solutions: Influence of electrode polarization and modeling. AB - Impedance spectroscopy was applied to determine glucose concentration in the interstitial fluid for its potential use in diabetic monitoring. For this purpose, the changes in the measured dielectric properties due to the presence of glucose in water and saline solutions were examined between 40 Hz and 110 MHz. Electrode polarization (EP) was a dominant factor which shaped the spectrum at low frequencies. A theoretical model of EP using a constant phase-angle-element produced excellent matches to the measured data. By fitting the measured data to the model, the relative permittivity (E(h)) and conductivity (sigma(l)) were obtained. For deionized water, the relative permittivity dropped from 80.1 to 73.2 and conductivity ranged between 0.142 and 0.212 mS/m when the glucose concentration was increased from 0 to 32 g/dl. For the same variation of glucose level in 0.15 M NaCl, E(h) was reduced from 79.8 to 71.5 and sigma(l) decreased from 1.384 to 0.522 S/m. Glucose level produced a definite change in dielectric properties. However, the changes within the physiological range of glucose (less than a few hundred mg/dl) were small and appeared to be within the measurement error. PMID- 21036028 TI - Highly selective recognition of naphthol isomers based on the fluorescence dye incorporated SH-beta-cyclodextrin functionalized gold nanoparticles. AB - In present work, a rhodamine 6G (Rh 6G)-incorporated beta-cyclodextrin functionalized gold nanoparticle (Rh 6G-CD-AuNP) based fluorescent assay has been successfully developed for recognizing/detecting the structural isomers, alpha naphthol and beta-naphthol, in aqueous solution. The beta-cyclodextrin functionalized gold nanoparticles (CD-AuNPs) are achieved by conjugating the thiolated beta-cyclodextrin (SH-beta-CD) with AuNPs via S-Au covalent bonds. Rhodamine 6G (Rh 6G) is chosen as a fluorescent probe in this approach because it can be strongly absorbed on the surface of AuNP by noncovalent interaction. After binding with beta-CD cavity, the naphthols enable to act as electron transfer quenchers of Rh 6G, which lead to significant fluorescence quenching of the dye. Because of different association ability of naphthol isomers with the beta-CD cavity, the assay can selectively distinguish alpha-naphthol and beta-naphthol with reasonable sensitivity. Detection of naphthols down to 8 nM with a dynamic range of nearly three orders of magnitude (0.01-8 MUM) for alpha-naphthol and 50 nM with two orders of magnitude (0.1-20 MUM) for beta-naphthol is demonstrated, respectively. The ability of the method for detecting the content of alpha naphthol or beta-naphthol in the different naphthol mixtures has also been evaluated. PMID- 21036029 TI - An electrochemical biosensor for the detection of tyrosine oxidation induced by Fenton reaction. AB - A simple and sensitive electrochemical biosensor was used to detect tyrosine oxidation induced by hydroxyl radicals generated by Fenton reaction (Fe(2+)/H(2)O(2)). Poly(glu, tyr) (4:1) peptides were immobilized on indium tin oxide (ITO) electrode surface via layer-by-layer assembly technique, and Os(bpy)(3)(2+)-mediated tyrosine oxidation current was employed as the signal reporter of the biosensor. It was found that the electrochemical signal of the peptide decreased markedly after incubation with Fenton reagents. Interestingly, L-dopa, the oxidation product of tyrosine, was likely to form complexes with Fe(III), which could suppress the electro-oxidation of L-dopa and resulted in decrease of current response. Our results indicate that the peptide damage involved two steps and was a second-order reaction. X-ray photoelectron spectroscopy was used to quantitatively determine nitrogen elemental percentage on peptide-coated electrode surface, which eliminated the possibility that signal decrease was caused by peptide backbone cleavage. Moreover, the lowest concentration of Fenton reagents that could be detected was 10 MUM Fe(2+) or H(2)O(2), similar to the level in vivo. We suggest that the biosensor can be used to detect protein damage induced by Fenton reaction. PMID- 21036030 TI - TiO2 nanowire FET device: encapsulation of biomolecules by electro polymerized pyrrole propylic acid. AB - Silane-based methods have become the standards for the conjugation of biomolecules, especially for the preparation of one-dimensional nanomaterial biosensors. However, the specific binding of those target molecules might raise problems with regard to the sensing and non-sensing regions, which may contaminate the sensing devices and decrease their sensitivity. This paper attempts to explore the encapsulation of biomolecules on a one-dimensional nanomaterial field effect transistor (FET) biosensor using polypyrrole propylic acid (PPa). Specifically, the encapsulation of biomolecules via the electropolymerization of pyrrole propylic acid (Pa), a self-made low-conductivity polymer, on TiO(2)-nanowire (NW)-based FETs is presented. The energy dispersive spectrum (EDS) was obtained and electrical analysis was conducted to investigate PPa entrapping anti-rabbit IgG (PPa/1 degrees Ab) on a composite film. The specificity, selectivity and sensitivity of the sensor were analyzed in order to determine the immunoreaction of PPa/1 degrees Ab immobilized NW biosensors. Our results show that PPa/1 degrees Ab achieved high specificity immobilization on NWs under the EDS analysis. Furthermore, the TiO(2)-NW FET immunosensor developed in this work successfully achieved specificity, selectivity and sensitivity detection for the target protein rabbit IgG at the nano-gram level. The combination of PPa material and the electropolymerization method may provide an alternative method to immobilize biomolecules on a specific surface, such as NWs. PMID- 21036031 TI - Imaging evaluation of the pregnant patient with suspected pulmonary embolism. AB - Pulmonary embolism is the leading cause of maternal death in the developed world. The clinical diagnosis of pulmonary embolism is particularly challenging in pregnant patients as physiologic changes of pregnancy can mimic symptoms of pulmonary embolism or deep venous thrombosis. Clinical decision and imaging algorithms for venous thromboembolic disease have been proposed in the literature for the general population, but have not undergone wide-scale validation in pregnant patients. Laboratory evaluation of D-dimer levels has likewise been established as a viable screening method in the general population but remains controversial in pregnant patients. Regardless of whether D-dimer levels are used in this population, the clinician must often rely on imaging tests to confirm or exclude a clinical suspicion of pulmonary embolism. Additional factors beyond test performance must be weighed during pregnancy: radiation exposure to the fetus and maternal breast tissue, the safety of intravenous contrast administration and the diagnostic accuracy of the various testing options so that diagnosis and proper management are not delayed. The epidemiology of pregnancy related venous thromboembolic disease and the different diagnostic methods are reviewed, with emphasis on the pregnant patient. Finally, a diagnostic imaging algorithm is proposed for the evaluation of the pregnant patient when a clinical suspicion of pulmonary embolism exists. PMID- 21036032 TI - Anesthetic management of parturients with defects in coagulation factor V. PMID- 21036033 TI - Systems biology of cellular rhythms: from cacophony to symphony. PMID- 21036034 TI - Effective biennial mammographic screening in women aged 40-49. AB - BACKGROUND: The United Kingdom is currently moving the age limit for invitation in its national breast screening programme downwards from 50 to 47. In contrast, the US Preventive Services Task Force concluded that, because of borderline statistical significance on effectiveness of mammographic screening, the current evidence is insufficient to advise screening in women aged 40-49. MATERIAL AND METHODS: We designed a case-referent study to investigate the effect of biennial mammographic screening on breast cancer mortality for women in their forties. In Nijmegen, the Netherlands, screening started in 1975. A total of 272 breast cancer deaths were identified, and 1360 referents aged 40-69 were sampled from the population invited for screening. Effectiveness was estimated by calculating the odds ratio (OR) indicating the breast cancer death rate in screened versus unscreened women. RESULTS: In women aged 40-49, the effect of screening was OR = 0.50 (95% confidence interval (CI) = 0.30-0.82). This result is similar to those aged 50-59 (OR = 0.54; 95% CI = 0.35-0.85) and 60-69 (OR = 0.65; 95% CI = 0.38 1.13). CONCLUSION: Our results add convincing evidence about the effectiveness of biennial mammographic screening in women aged 40-49. PMID- 21036035 TI - Improved biohydrogen production with an expression of codon-optimized hemH and lba genes in the chloroplast of Chlamydomonas reinhardtii. AB - According to the codon bias in the chloroplast genome of Chlamydomonas reinhardtii, the codon-optimized coding regions of both the ferrochelatase gene, hemH, from Bradyrhizobium japonicum and the leghemoglobin gene, lba, from Glycine max were synthesized de novo and transferred into the chloroplast of C. reinhardtii. The expression level of hemH-lba protein was improved by 6.8 folds in the codon-optimized transgenic alga compared with the non-optimized one under both normal and anaerobic conditions. H(2) yield was 22% and the respiration rate was 44% higher in the codon-optimized transgenic algal cultures than those of the non-optimized ones, and was 450% and 134% higher than those of the control cultures, respectively. The transcript levels of hydA1 and hydA2 in the hemH-lba transgenic alga were also more stable and higher than those of the control alga. These results demonstrate that codon optimization increased the expression level of hemH-lba protein in the chloroplast of C. reinhardtii and improved algal H(2) yield by enhancing the respiration rate resulting in low O(2) content in the medium and up regulation of the expression of hydA1 and hydA2 in cells, thereby confirming the potential of the utilization of leghemoglobins for H(2) production in green algae. PMID- 21036036 TI - High hydrogen production rate of microbial electrolysis cell (MEC) with reduced electrode spacing. AB - Practical applications of microbial electrolysis cells (MECs) require high hydrogen production rates and a compact reactor. These goals can be achieved by reducing electrode spacing but high surface area anodes are needed. The brush anode MEC with electrode spacing of 2 cm had a higher hydrogen production rate and energy efficiency than an MEC with a flat cathode and a 1-cm electrode spacing. The maximum hydrogen production rate with a 2 cm electrode spacing was 17.8 m(3)/m(3)d at an applied voltage of E(ap)=1 V. Reducing electrode spacing increased hydrogen production rates at the lower applied voltages, but not at the higher (>0.6 V) applied voltages. These results demonstrate that reducing electrode spacing can increase hydrogen production rate, but that the closest electrode spacing do not necessarily produce the highest possible hydrogen production rates. PMID- 21036037 TI - Enhancement of wood waste decomposition by microbial inoculation prior to vermicomposting. AB - To investigate the feasibility of microbial pre-decomposition of timber wastes to quality production of vermicompost with higher agronomic value, timber wastes were inoculated with different combinations of the fungi Phanerochete chrysosporium, Trichoderma reesei, Aspergillus niger and the bacteria Azotobacter chroococcum (MTCC 3853) and Bacillus cereus (MTCC 4079) and incubated at 28-30 degrees C in a mechanical composter. The inoculation enhanced the degradation of timber wastes, increased total nitrogen and improved the quality and enhanced production of vermicompost generated with the native earthworm Drawida willsi Michelsen. Total nitrogen increased from 0.16% to 1.52% and total organic carbon (TOC) decreased from 42% to 13%. Out of 10 microbial combinations tested for pre decomposition, the combination of P. chrysosporium+T. reesei was found best in terms of ligno-cellulosic decomposition, and P. chrysosporium+A. niger+B. cereus with respect of cast output. The study shows that microbial pre-decomposition of timber wastes to produce quality vermicompost is a feasible technology. PMID- 21036038 TI - Effects of ensilage on storage and enzymatic degradability of sugar beet pulp. AB - Ensiling was investigated for the long-term storage of Sugar Beet Pulp (SBP). Eight strains of lactic acid bacteria (LAB) and a non-inoculated control were screened based on their ability to rapidly reduce pH, produce a large amount of lactic acid and inhibit undesirable fermentations. Lactobacillus brevis B-1836 (LAB #120), Lactobacillus fermentum NRRL B-4524 (LAB #137) and a non-inoculated control were selected for further research to determine the effects of LAB inoculation level and packing density on SBP silage quality and sugar yield upon enzymatic hydrolysis. Both SBP preservation and prevention of cellulose and hemicellulose loss were better when SBP was treated with LAB #137 compared to LAB #120 and the non-inoculated control. Additionally, the ensiling process was found to significantly improve the enzymatic digestibility of SBP by as much as 35%. The results suggest that ensiling may be a promising technology for SBP stabilization and pretreatment for bioconversion to products. PMID- 21036039 TI - Fate of organic carbon in UAFB treating raw sewage: impact of moderate to low temperature. AB - The anaerobic biological treatment of raw sewage under low ambient temperatures was investigated in an up-flow anaerobic fixed bed (UAFB) reactor, over a 220-day trial period. The operating temperature was lowered stepwisely from 35 to 25, 20 and 15 degrees C. Obvious accumulation of acetic acid was observed in the effluent as the temperature dropped, which almost tripled at 15 degrees C compared to that at 35 degrees C. An interesting psychrophilic-forward-shift trend of methane production rate following the decrease of temperature was discovered. The methane yield at each trial was 169, 201, 256 and 269 L(STP) CH(4)/kg COD(removed). For each temperature trial, about 32.6%, 28.3%, 34.4% and 34.9% were removed in form of methane. Based on PCR-DGGE results, the band corresponded to Methanosphaera spp. only showed up on 15 degrees C profile. Analysis of both methane production and DGGE results indicated that psychro tolerant microorganisms dominated the archaeal populations in the UAFB under low temperature. PMID- 21036040 TI - Inhibition of human neuraminidase 3 (NEU3) by C9-triazole derivatives of 2,3 didehydro-N-acetyl-neuraminic acid. AB - We report the synthesis of a series of C9 and N5Ac modified analogs of 2,3 didehydro-N-acetyl-neuraminic acid (DANA) and their inhibitory potency for the human neuraminidase 3 (NEU3) enzyme. We were able to generate a small library of compounds through the synthesis of azide derivatives of DANA, followed by Cu catalyzed azide-alkyne cycloaddition (CuAAC) to generate triazole-containing inhibitors. Our results suggest that NEU3 can tolerate large hydrophobic groups at the C9 position; however, none of the derivatives made at the N5Ac side-chain were active. We identify three new inhibitors that have comparable potency to the best reported inhibitors of the enzyme. PMID- 21036041 TI - Synthesis of potent, substituted carbazoles as selective androgen receptor modulators (SARMs). AB - The synthesis and in vitro binding affinity for a novel series of potent androgen receptor modulators is described. One of the more potent compounds (17, RAD35010) was further characterized in vivo where it restored levator ani weight in castrated male rats to near sham level while having no significant effect on prostate weight. PMID- 21036042 TI - Azaindole N-methyl hydroxamic acids as HIV-1 integrase inhibitors-II. The impact of physicochemical properties on ADME and PK. AB - HIV-1 integrase is one of three enzymes encoded by the HIV genome and is essential for viral replication, and HIV-1 IN inhibitors have emerged as a new promising class of therapeutics. Recently, we reported the discovery of azaindole hydroxamic acids that were potent inhibitors of the HIV-1 IN enzyme. N-Methyl hydroxamic acids were stable against oxidative metabolism, however were cleared rapidly through phase 2 glucuronidation pathways. We were able to introduce polar groups at the beta-position of the azaindole core thereby altering physical properties by lowering calculated log D values (c Log D) which resulted in attenuated clearance rates in human hepatocytes. Pharmacokinetic data in dog for representative compounds demonstrated moderate oral bioavailability and reasonable half-lives. These ends were accomplished without a large negative impact on enzymatic and antiviral activity, thus suggesting opportunities to alter clearance parameters in future series. PMID- 21036043 TI - The discovery of new spirocyclic muscarinic M3 antagonists. AB - The optimisation of a new series of high potency muscarinic M3 antagonists, derived from high throughput screening library hit is described. PMID- 21036044 TI - Discovery of INCB3344, a potent, selective and orally bioavailable antagonist of human and murine CCR2. AB - Rational design based on a pharmacophore of CCR2 antagonists reported in the literature identified lead compound 9a with potent inhibitory activity against human CCR2 (hCCR2) but moderate activity against murine CCR2 (mCCR2). Modification on 9a led to the discovery of a potent CCR2 antagonist 21 (INCB3344) with IC(50) values of 5.1 nM (hCCR2) and 9.5 nM (mCCR2) in binding antagonism and 3.8 nM (hCCR2) and 7.8 nM (mCCR2) in antagonism of chemotaxis activity. INCB3344 exhibited >100-fold selectivity over other homologous chemokine receptors, a free fraction of 24% in human serum and 15% in mouse serum, and an oral bioavailability of 47% in mice, suitable as a tool compound for target validation in rodent models. PMID- 21036045 TI - N-(8-(3-ethynylphenoxy)octyl-1-deoxynojirimycin suppresses growth and migration of human lung cancer cells. AB - Previously N-(8-(3-ethynylphenoxy)octyl-1-deoxynojirimycin 1 has been shown to display properties associated with inhibition of angiogenesis. Here we examined the anti-tumourigenic role of 1 in a lung cancer cell line. This agent altered cell surface oligosaccharide expression and inhibited the growth of A549 cells by inducing G1 phase cell cycle arrest and apoptosis. Furthermore, stress fibre assembly and cell migration in A549 cells was markedly suppressed by 1. PMID- 21036046 TI - Running injury and stride time variability over a prolonged run. AB - Locomotor variability is inherent to movement and, in healthy systems, contains a predictable structure. In this study, detrended fluctuation analysis (DFA) was used to quantify the structure of variability in locomotion. Using DFA, long range correlations (alpha) are calculated in over ground running and the influence of injury and fatigue on alpha is examined. An accelerometer was mounted to the tibia of 18 runners (9 with a history of injury) to quantify stride time. Participants ran at their preferred 5k pace+/-5% on an indoor track to fatigue. The complete time series data were divided into three consecutive intervals (beginning, middle, and end). Mean, standard deviation (SD), coefficient of variation (CV) and alpha of stride times were calculated for each interval. Averages for all variables were calculated per group for statistical analysis. No significant interval, group or interval*group effects were found for mean, SD or CV of stride time. A significant linear trend in alpha for interval occurred with a reduction in alpha over the course of the run (p=0.01) indicating that over the run, stride times of runners became more unpredictable. This was likely due to movement errors associated with fatigue necessitating frequent corrections. The injured group exhibited lower alpha (M=0.79, CI(95)=0.70, 0.88) than the non-injured group (p=0.01) (M=0.96, CI(95)=0.88, 1.05); a reduction hypothesized to be associated with altered complexity. Overall, these findings suggest injury and fatigue influence neuromuscular output during running. PMID- 21036047 TI - Joint moment contributions to swing knee extension acceleration during gait in individuals with spastic diplegic cerebral palsy. AB - The mechanisms contributing to swing phase knee acceleration in individuals with spastic diplegic cerebral palsy (CP) are not well understood, but evidence suggests that selective voluntary motor control (SVMC) may play a role. The purpose of this study was to examine the relationship between lower limb SVMC, measured using Selective Control Assessment of the Lower Extremity (SCALE), and joint moment contributions to swing knee extension acceleration in participants with spastic diplegic CP. Eighteen participants were recruited (mean age=13.8 years, range=6-30 years, Gross Motor Function Classification System Levels I III). Induced acceleration analysis was performed during the swing phase of gait. Average joint moment contributions to swing knee extension acceleration were calculated. Contributions from stance limb and swing limb joint moments were correlated with SCALE scores using Pearson's correlations. A strong correlation was found (p<0.0001, r=0.85) between SCALE score and the total swing joint moment contributions to swing knee extension acceleration. As SCALE score increased, swing joint moments provided less resistance to knee extension acceleration. No relationship (p=0.18) was found between stance moment contributions to swing knee acceleration and stance limb SCALE scores. Excessive contributions from swing limb joint moments appear to be the factor limiting swing knee extension in spastic diplegic CP gait. Interventions that address negative contributions due to spasticity may not be effective in patients who cannot generate adequate knee extension due to poor SVMC. PMID- 21036048 TI - Opening- or closing-wedged high tibial osteotomy: a meta-analysis of clinical and radiological outcomes. AB - High tibial osteotomy (HTO) has been advocated for the treatment of isolated medial compartment osteoarthritis of the knee. Debate remains over the superiority of performing a medial opening-wedge or lateral closing-wedge HTO. The purpose of this study was to compare the clinical and radiological outcomes, and complications of patients following opening-wedge compared to closing-wedge HTO. A systematic review was undertaken of published and unpublished literature databases from their inception to May 2010. Twelve papers reporting nine clinical trials were found to be suitable for meta-analysis comparing 324 opening-wedge HTOs to 318 closing-wedge HTOs. There was no difference in the incidence of infection, deep vein thrombosis, peroneal nerve palsy, non-union or revision to knee arthroplasty (p>0.05). There was however a significantly greater posterior tibial slope and mean angle of correction, reduced patellar height and hip-knee ankle angle following opening-wedge HTO (p<0.05). No significant difference was found for any clinical outcome including pain, functional score or complications (p>0.05). PMID- 21036049 TI - Bisaryldiketene derivatives: A new class of selective ligands for c-myc G quadruplex DNA. AB - A series of bisaryldiketene derivatives were designed and synthesized as a new class of specific G-quadruplex ligands. The ligand-quadruplex interactions were further evaluated by FRET, ITC, and PCR stop assay. In contrast to most of the G quadruplex ligands reported so far, which comprise an extended aromatic ring, these compounds are neither polycyclic nor macrocyclic, but have a non-aromatic and relative flexible linker between two quinoline moieties enabling the conformation of compounds to be flexible. Our results showed that these bisaryldiketene derivatives could selectively recognize G-quadruplex DNA rather than binding to duplex DNA. Moreover, they showed promising discrimination between different G-quadruplex DNA. The primary binding affinity of ligand M2 for c-myc G-quadruplex DNA was over 200 times larger than that for telomere G quadruplex DNA. PMID- 21036051 TI - Low voltage high-resolution SEM (LVHRSEM) for biological structural and molecular analysis. AB - High-resolution scanning electron microscopy (HRSEM) is being used increasingly to gain new insights into three-dimensional organization of biological structure, macromolecular complexes and interactions of cellular components as well as isolated cell organelles. Modern scanning electron microscopes (SEMs) combined with adequate sample preparation can now provide resolution comparable with that achieved using transmission electron microscopes (TEMs) down to 2-5 nm for biological material. The versatility of the instrument and new sample preparation techniques have allowed detailed analysis of chromosomes, cytoskeletal components, virus and other biological material that has not been possible with TEM. The present review addresses resolution and specific specimen preparations for HRSEM, and highlights the importance of specimen preparation and choice of methods to achieve optimal results for proteins, macromolecular complexes and subcellular structures using low voltage HRSEM (LVHRSEM). PMID- 21036050 TI - Structure and biological evaluation of novel cytotoxic sterol glycosides from the marine red alga Peyssonnelia sp. AB - Bioactivity-guided fractionation of the extract from a Fijian red alga Peyssonnelia sp. led to the isolation of two novel sterol glycosides 19-O-beta-d glucopyranosyl-19-hydroxy-cholest-4-en-3-one (1) and 19-O-beta-d-N-acetyl-2 aminoglucopyranosyl-19-hydroxy-cholest-4-en-3-one (2), and two known alkaloids indole-3-carboxaldehyde (3) and 3-(hydroxyacetyl)indole (4). Their structures were characterized by 1D and 2D NMR and mass spectral analysis. The sterol glycosides inhibited cancer cell growth with mean IC50 values (for 11 human cancer cell lines) of 1.63 and 1.41MUM for 1 and 2, respectively. The most sensitive cancer cell lines were MDA-MB-468 (breast) and A549 (lung), with IC50's in of 0.71-0.97MUM for 1 and 2. Modification of the sterol glycoside structures revealed that the alpha,beta-unsaturated ketone at C-3 and oxygenation at C-19 of 1 and 2 are crucial for anticancer activity, whereas the glucosidic group was not essential but contributed to enhanced activity against the most sensitive cell lines. PMID- 21036052 TI - Histological assessment of SJL/J mice treated with the antioxidants coenzyme Q10 and resveratrol. AB - The muscular dystrophies (MDs) are genetic disorders of muscle degeneration due to mutations in genes that encode a wide variety of proteins. Dysferlinopathy are characterized by the absence of dysferlin in skeletal muscle and an autosomal recessive mode of inheritance. Both histological and ultrastructural pathology have been well established in dysferlinopathy patients and dysferlin-deficient animal models. To our knowledge the effect of antioxidant supplementation on this level has not been described previously. This article therefore focuses on the histopathology to reveal the effect of antioxidant supplementation. The study aimed to determine, at cellular level, the histopathological changes in the SJL/J mouse model following a 90 day trial with antioxidant supplementation. Markedly reduced inflammatory insult in the more affected quadriceps muscles of animals treated with high doses of CoQ10 and a combination of resveratrol/CoQ10 were observed. The outcome provides evidence that high doses of antioxidant supplementation resulted in decreased dystrophic markers and enhanced tissue integrity at cellular level. PMID- 21036053 TI - Activity determination and nuclear decay data of (113m)Cd. AB - The radionuclide (113m)Cd was extracted from a Cd component, which has been irradiated in a research reactor during its routine operation. A validated separation procedure was then used to obtain a (113m)Cd solution of high radiochemical purity. The solution was measured by means of liquid scintillation counting for activity determination. To this end, the CIEMAT/NIST efficiency tracing method as well as the triple-to-double coincidence (TDCR) counting technique were used. Measurements in a low-background gamma-ray spectrometer were applied to identify any potential photon-emitting impurities and to measure the 263.7 keV photons from the isomer transition. A gamma emission probability of 0.01839(29)% was determined for this line. The liquid scintillation measurements were also used to evaluate the half-life of (113m)Cd. The decay was followed for about 11 months and a half-life T(1/2)=13.97(13) years was obtained. PMID- 21036054 TI - FBX aqueous chemical dosimeter for measurement of dosimetric parameters. AB - We investigated the ferrous sulphate-benzoic acid-xylenol orange (FBX) aqueous chemical dosimeter for measurement of dosimetric parameters such as the output factor, backscatter factor and lateral beam profiles for different square fields sizes for (60)Co gamma-rays. A water phantom was employed to measure these parameters. An ionization chamber (IC) was used for calibration and comparison. A comparison of the resulting measurements with an ionization chamber's measured parameters showed good agreement. We thus believe that the tissue equivalent FBX dosimetry system can measure the dosimetric parameters for (60)Co with reasonable accuracy. PMID- 21036055 TI - Transaortic chordae and pannus removal without redo mitral valve replacement in prosthetic mitral valve malfunction. AB - Both anterior and posterior chordae of the mitral valve are occasionally spared during mitral valve surgery to preserve left ventricular function. In this report, a 43-year-old woman who had undergone mitral valve replacement surgery with anterior and posterior chordal preservation 9 years ago subsequently had mitral valve pannus and anterior chordae covering the prosthetic valve, which led to valve malfunction. Prosthetic mitral valve function was successfully recovered by performing transaortic pannus and chordae removal, avoiding redo mitral valve replacement. PMID- 21036057 TI - Waldenstrom's macroglobulinemia. An overview of its clinical, biochemical, immunological and therapeutic features and our series of 121 patients collected in a single center. AB - Waldenstrom's macroglobulinemia (WM) is defined as a B-cell lymphoproliferative disorder characterized by lymphoplasmacytic infiltration of the bone marrow associated with a monoclonal IgM component in the serum. Its clinical presentation is marked by diffuse clonal cell expansion, as well as by the physical and chemical properties of the monoclonal component, its autoantibody activity and possible tissue deposition. Initiation of treatment is not determined by the monoclonal IgM level, nor the extent of bone marrow infiltration, but confined to symptomatic patients. Their median overall survival ranges from 5 to 10 years. Poor outcome predictors include advanced age, low hemoglobin levels, low platelet count, high beta2-microglobulin and high concentration of the serum monoclonal component. First-line therapeutic approaches include alkylating agents (chlorambucil, melphalan, cyclophosphamide), nucleoside analogs (fludarabine, cladribrine), and rituximab, whether singly or combined. Thalidomide-based regimens and bortezomib have also been assessed, and new agents such as bendamustine and everolimus are being investigated. We review these general features and describe our series of 121 patients with clearly established WM. PMID- 21036058 TI - First-line chemotherapy for metastatic breast cancer in patients >=75 years: a retrospective single-centre analysis. AB - Data on chemotherapy for elderly patients with metastatic breast carcinoma (MBC) are limited. We performed a 7-year retrospective analysis of MBC patients at our institution receiving first-line chemotherapy aged >=75 years. Of 117 patients, 103 received monotherapy (67 capecitabine, 29 vinorelbine, 5 docetaxel, 2 liposomal doxorubicin) and 14 received polychemotherapy (12 anthracycline-based, 2 vinorelbine-gemcitabine). Chemotherapy demonstrated acceptable tolerability. Median progression-free survival (PFS) and overall survival (OS) from initiation of chemotherapy were 6.2 months and 13.8 months, respectively. At 2 years, 25% of patients were alive; however, 25% died within 3 months of beginning chemotherapy. Independent prognostic factors for longer PFS were good performance status, absence of visceral disease and capecitabine treatment. Good performance status and lack of visceral disease were also significant for OS. These results suggest that palliative chemotherapy should not be systematically excluded in this setting, but should be carefully discussed as it appears to be feasible with apparent benefit in selected patients. PMID- 21036059 TI - Temporal and spatial regulatory functions of the V(D)J recombinase. AB - In developing lymphocytes, V(D)J recombination is subject to tight spatial and temporal regulation. An emerging body of evidence indicates that some of these constraints, particularly with respect to locus specificity and cell cycle phase, are enforced by regulatory cues that converge directly on the RAG proteins themselves. Active chromatin is bound by RAG-2 through a specific histone modification that may serve the recombinase as an allosteric activator as well as a docking site. RAG-1 possesses intrinsic histone ubiquitin ligase activity, suggesting that the recombinase not only responds to chromatin modification but is itself able to modify chromatin. The cyclin A/Cdk2 component of the cell cycle clock triggers periodic destruction of RAG-2, thereby restricting V(D)J recombination to the G0/G1 cell cycle phases. These examples illustrate that the RAG proteins, in addition to their direct actions on DNA, are able to detect and respond to intracellular signals, thereby coordinating recombinase activity with intracellular processes such as cell division and transcription. PMID- 21036060 TI - Upper and lower extremity proprioceptive inputs modulate EMG activity of the trapezius. AB - Axial muscles like the trapezius have different reflexive and functional properties. The aim of this study was to analyze the long latency reflexes obtained from the trapezius by the electrical stimulation of upper and lower extremity peripheral nerves. Thirty-one healthy volunteers were included in the study. Surface EMG activity of both trapezius muscles was recorded and averaged after electrical stimulation of the median and peroneal mixed nerves. The recordings were performed during supine and erect posture in nine subjects to evaluate of the effect of postural differences on reflex response. Reflex recordings were also performed in six subjects from some other muscles together with the trapezius by the stimulation of the peroneal nerve. Reflex responses including three components were recorded from the trapezius muscle (unilateral or bilateral) by electrical stimulation of the peroneal nerve. The most stable of them was the second component (23/31) which had a latency of 72.6 +/- 7.9 ms for the ipsilateral, and 74.2 +/- 8.5 ms for the contralateral trapezius (15/31). For median stimulation, the first component recorded at 32.0 +/- 6.7 ms was the most stable (25/31). The second component was more frequently recorded on the contralateral side (14/31). Erect posture increased the amplitude of these components. Upper and lower extremity proprioceptive inputs modulate the EMG activity of the trapezius. This modulation probably related with postural adjustments. PMID- 21036061 TI - Seizures after cardiac surgery. AB - INTRODUCTION: Cardiac surgery, mainly in the form of coronary artery bypass graft surgery, is known to be associated with a risk of injury to the central and peripheral nervous systems. The most commonly encountered central nervous system injury associated with cardiac surgery continues to be stroke, with seizures occurring less commonly but with significant consequences. Seizures in the cardiac surgery recovery unit (CSRU) always cause great concern to the attending physicians and families of the patient. Therefore, it is of critical importance that the attending physician has an accurate and efficient approach to the differential diagnosis, investigations, and management of these patients, who represent a unique group requiring specific investigations and management. METHODS: A review and discussion of experience with seizures in the CSRU. DISCUSSION: Cardiac surgery poses a significant threat to the nervous system through various mechanisms although newer technologies and surgical techniques have led to improved outcomes in recent years. Although the incidence of seizures remains low, the causes and management are relatively unique in this setting, including a probable "toxic syndrome" related to certain antibiotics or other perioperative drugs such as tranexamic acid. A targeted approach based on recognizing focal versus generalized seizures, a careful review of history and medications, and a focused workup will lead the clinician to choosing the most effective therapy when one is required. Special concerns regarding the side effect profile of phenytoin in this setting have led to valproate and levetiracetam becoming useful alternatives, which are effective and well tolerated. The incidence of nonconvulsive seizures in the CSRU remains to be elucidated with prospective monitoring studies, as does their effect on outcome. PMID- 21036062 TI - Post-mitral valve replacement intramural left atrial lesion. PMID- 21036063 TI - Immediate extubation after off-pump coronary artery bypass graft surgery in 1,196 consecutive patients: feasibility, safety and predictors of when not to attempt it. AB - OBJECTIVE: The purpose of this study was to evaluate the feasibility and safety of immediate extubation (ultrafast-track anesthesia [UFTA]) in the operating room, and the predictors of when not to attempt it in patients undergoing off pump coronary artery bypass graft surgery (OPCAB). DESIGN: Case series. SETTING: A private hospital. PARTICIPANTS: One thousand one hundred ninety-six patients undergoing OPCAB surgery, representing 4 years of a single anesthesia service's practice (3 anesthesiologists), were evaluated for immediate extubation. All patients were considered amenable to immediate extubation if specific criteria were met. INTERVENTION: Patients received general anesthesia (UFTA protocol) and underwent off-pump coronary artery bypass graft surgery. MEASUREMENTS AND MAIN RESULTS: One thousand sixty-five patients (89%) met extubation criteria and were extubated successfully in the operating room. By multivariate analysis, the following independent predictors of avoiding immediate extubation were identified: reoperation (odds ratio [OR] = 3.9, p < 0.001), pre-existing renal disease (OR = 3.1, p < 0.0001), diabetes (OR = 1.7, p < 0.007), preoperative intra-aortic balloon pump placement (OR = 7.4, p < 0.0001), and total surgical time (OR = 3.7, p < 0.0001). Patients who met extubation criteria had lower in hospital reintubation (2.5% v 16%, p < 0.001), myocardial infarction (1.03% v 4.58%, p = 0.001), renal insufficiency (2.2% v 7.63%, p < 0.001), stroke (0.4% v 2.29%, p = 0.032), and mortality rates (1.2% v 10.7%, p < 0.001) than patients who did not. CONCLUSIONS: UFTA is feasible and safe in most patients undergoing OPCAB surgery. Baseline and intraoperative data predicted when immediate extubation should not be attempted. PMID- 21036064 TI - The role of thoracic epidural blockade in predicting responsiveness to left sympathetic denervation in patients with catecholaminergic polymorphic ventricular tachycardia. PMID- 21036065 TI - Anesthetic management of transcatheter aortic valve implantation with transaxillary approach. AB - OBJECTIVE: To describe the anesthetic management of transcatheter aortic valve implantation (TAVI) with the transaxillary approach. DESIGN: An observational cohort study. SETTING: Two university hospitals. PARTICIPANTS: Twenty-two patients with severe aortic stenosis (+/- regurgitation) at high risk for surgical valve replacement, with contraindications for transfemoral TAVI (81 +/- 4.9 years; logistic EuroSCORE, 27% +/- 16.9%). INTERVENTION: General anesthesia or local anesthesia plus sedation followed by postoperative care. MEASUREMENTS AND MAIN RESULTS: Local anesthesia plus sedation and general anesthesia were used in 14 and 8 patients, respectively. Two patients undergoing local anesthesia were monitored with transesophageal echocardiography and supported with noninvasive mask ventilation during the procedure. Main complications included hemodynamic instability requiring inotropes (2 patients), severe postimplant aortic regurgitation requiring immediate second valve-in-valve implantation (1 patient), valve embolization requiring open-valve surgery (1 patient), subclavian artery dissection compromising the flow to a mammary artery graft (1 patient), ascending aortic dissection (1 patient), stroke (2 patients), and atrioventricular block requiring pacemaker implantation (3 patients). Four patients experienced an increased (baseline value * 1.5) postoperative serum creatinine. Five patients required red blood cell tranfusions (2 units). Intensive care unit stay and hospital stay were 6 (4-23) hours and 8 (8-9) days, respectively. All patients were alive 30 days after the procedure. The 6-month mortality was 9%. CONCLUSIONS: Transaxillary TAVI is feasible in high-risk patients with aortic stenosis and peripheral vasculopathy. Nevertheless, severe procedural complications are possible, and anesthesiologists should be prepared to assist in the management of these conditions. PMID- 21036066 TI - Right-to-left ventricular end-diastolic diameter ratio and prediction of right ventricular failure with continuous-flow left ventricular assist devices. AB - BACKGROUND: Left ventricular assist device (LVAD) implantation is an accepted therapy for patients with end-stage heart failure. Post-operative right ventricular failure (RVF) still remains a major cause of morbidity and mortality in these patients. This study sought to identify echocardiography parameters to select patients with high risk of RVF after LVAD implantation. METHODS: Prospectively collected pre-operative transesophageal echocardiography (TEE) and clinical data were evaluated in patients pre-selected for isolated LVAD or biventricular assist device (BiVAD) implantation. According to prevalence of RVF during the first post-operative 48 hours, patients were divided into those who developed RVF (isolated LVAD with RVF) and those who did not (isolated LVAD without RVF). Echocardiographic parameters for RV geometry, RV function, LV geometry, and the RV-to-LV end-diastolic diameter ratio (R/L ratio) were evaluated. For identification of the optimal cutoff of R/L ratio, receiver operating characteristics curves were constructed. RESULTS: An isolated LVAD was implanted in 115 patients and BiVAD in 22 patients. RVF developed in 15 patients (13%) after isolated LVAD implantation. The R/L ratio was markedly increased in the isolated LVAD with RVF and BiVAD groups compared with the isolated LVAD without RVF group. According to the receiving operating curve, the cutoff for the R/L ratio to predict RVF was 0.72. The odds ratio that RVF will develop is 11.4 in patients with an R/L ratio >0.72 (p = 0.0001). CONCLUSIONS: Increased R/L ratio successfully identifies patients with high risk of RVF after isolated LVAD implantation. Beyond standard measurements of RV function, the consideration of R/L ratio may be useful to improve risk stratification in patients before isolated LVAD implantation. PMID- 21036067 TI - Would access to device therapies improve transplant outcomes for adults with congenital heart disease? Analysis of the United Network for Organ Sharing (UNOS). AB - BACKGROUND: Patients with congenital heart disease (CHD) now survive into adulthood and often present with end-stage heart failure (HF). HF management and approach to orthotopic heart transplant (OHT) may differ from adults without CHD. We sought to compare OHT waitlist characteristics and outcomes for these 2 groups. METHODS: The Organ Procurement and Transplantation Network (OPTN)/United Network for Organ Sharing (UNOS) database was used to identify adults (>=18 years) listed for OHT from 2005 to 2009. The cohort was divided into those with or without CHD. RESULTS: Of 9,722 adults included, 314 (3%) had CHD. Adults with CHD were younger (35 +/- 13 vs 52 +/- 12 years, p < 0.01) and more often had undergone prior cardiac surgery (85% vs. 34%, p < 0.01). Patients with CHD were less likely to have a defibrillator (44% vs 75%, p < 0.01) or ventricular assist device (5% vs 14%, p < 0.01) and were more likely to be listed at the lowest urgency status than patients without CHD (64% vs 44%, p < 0.01). Fewer CHD patients achieved OHT (53% vs 65%, p < 0.001). Although overall waitlist mortality did not differ between groups (10% vs 8%, p = 0.15), patients with CHD were more likely to experience cardiovascular death (60% vs 40%, p = 0.03), including sudden in 44% and due to HF in 16%. CONCLUSIONS: Despite lower urgency status, patients with CHD have greater cardiovascular mortality awaiting OHT than those without. Increased defibrillator use could improve survival to OHT, because sudden death is common. VAD support may benefit select patients, but experience in CHD is limited. Referral to specialized adult congenital heart centers can enhance utilization of device therapies and potentially improve waitlist outcomes. PMID- 21036069 TI - Laparoscopic surgery performed through a single incision: a systematic review of the current literature. PMID- 21036070 TI - Survival of the fittest: the hidden cost of undertriage of major trauma. AB - BACKGROUND: Injured patients cared for in trauma centers have a lower risk of death than those cared for in nontrauma centers. However, many patients are transported to a non-trauma center after injury (undertriaged) and require transfer to trauma center care. Previous analyses of undertriage focused only on survivors to trauma center care and were potentially subject to survivor bias. Using a novel population-based design, we evaluated the true mortality cost of undertriage. STUDY DESIGN: We used a retrospective cohort design and included all severely injured patients surviving to reach an emergency department within the province of Ontario, Canada. Those patients who were triaged to a non-trauma center as their first hospital exposure were the Undertriage cohort. Undertriage cohort patients were either transferred to a trauma center (Transfer cohort) or died before transfer could be accomplished (emergency department-death cohort). Patients that were transported directly from the scene of injury to a trauma center represented the Direct cohort. Thirty-day mortality in undertriaged patients was analyzed using two approaches: allowing for survivor bias (Transfer versus Direct) and without survivor bias (Undertriage versus Direct). RESULTS: Among 11,398 patients, 66% were transported directly to a trauma center and 30% were transferred. Four percent died before transfer (22% of all deaths). Reproducing approaches that ignore survivor bias, mortality in the Transfer and Direct cohorts was equivalent. However, unbiased assessment demonstrated that mortality was significantly higher in the Undertriage cohort than the Direct cohort (odds ratio = 1.24; 95% CI, 1.10-1.40). CONCLUSIONS: Undertriage after major trauma is associated with substantial mortality. These data suggest a need to design strategies to improve triage to trauma center. PMID- 21036071 TI - A moderated journal club is more effective than an Internet journal club in teaching critical appraisal skills: results of a multicenter randomized controlled trial. AB - BACKGROUND: Evidence Based Reviews in Surgery (EBRS) is an Internet journal club that is effective in teaching critical appraisal skills to practicing surgeons. The objective of this randomized controlled trial was to determine whether teaching critical appraisal skills to surgical residents through the Internet is as effective as a moderated in-person journal club. STUDY DESIGN: Twelve general surgery programs were cluster-randomized to an Internet group (6 programs; 227 residents; 23 to 47 residents/program) or a moderated journal club (6 programs, 216 residents, 21 to 72 residents/program). Each EBRS package includes a clinical and methodological article plus clinical and methodological reviews. Residents in the Internet group were required to complete 8 EBRS packages online plus participate in an online discussion group. Residents in the moderated group were required to attend 8 journal clubs moderated by a faculty member. All residents completed a validated test assessing expertise in critical appraisal. RESULTS: In the Internet group, only 18% of residents completed at least 1 EBRS package compared with 96% in the moderated group. One hundred and thirty (57.8%) residents in the Internet group completed the test compared with 157 (72.7%) in the moderated group. The residents in the moderated group scored considerably better on the critical appraisal test, with a mean score of 42.1 compared with 37.4 in the Internet group (p = 0.05), with a moderate effect size of 0.6 SD. CONCLUSIONS: A moderated journal club is considerably better in teaching critical appraisal skills to surgical residents. This is likely because of the low participation in the Internet journal club. PMID- 21036072 TI - Mesh fixation in laparoscopic incisional hernia repair: glue fixation provides attachment strength similar to absorbable tacks but differs substantially in different meshes. AB - BACKGROUND: Laparoscopic ventral hernia repair has gained popularity among minimally invasive surgeons. However, mesh fixation remains a matter of discussion. This study was designed to compare noninvasive fibrin-glue attachment with tack fixation of meshes developed primarily for intra-abdominal use. It was hypothesized that particular mesh structures would substantially influence detachment force. STUDY DESIGN: For initial evaluation, specimens of laminated polypropylene/polydioxanone meshes were anchored to porcine abdominal walls by either helical titanium tacks or absorbable tacks in vitro. A universal tensile testing machine was used to measure tangential detachment forces (TF). For subsequent experiments of glue fixation, polypropylene/polydioxanone mesh and 4 additional meshes with diverse particular mesh structure, ie, polyvinylidene fluoride/polypropylene mesh, a titanium-coated polypropylene mesh, a polyester mesh bonded with a resorbable collagen, and a macroporous condensed PTFE mesh were evaluated. RESULTS: TF tests revealed that fibrin-glue attachment was not substantially different from that achieved with absorbable tacks (median TF 7.8 Newton [N], range 1.3 to 15.8 N), but only when certain open porous meshes (polyvinylidene fluoride/polypropylene mesh: median 6.2 N, range 3.4 to 10.3 N; titanium-coated polypropylene mesh: median 5.2 N, range 2.1 to 11.7 N) were used. Meshes coated by an anti-adhesive barrier (polypropylene/polydioxanone mesh: median 3.1 N, range 1.7 to 5.8 N; polyester mesh bonded with a resorbable collagen: median 1.3 N, range 0.5 to 1.9 N), or the condensed PTFE mesh (median 3.1 N, range 2.1 to 7.0 N) provided a significantly lower TF (p < 0.01). CONCLUSIONS: Fibrin glue appears to be an appealing noninvasive option for mesh fixation in laparoscopic ventral hernia repair, but only if appropriate meshes are used. Glue can also serve as an adjunct to mechanical fixation to reduce the number of invasive tacks. PMID- 21036073 TI - Advanced laparoscopic techniques significantly improve function of peritoneal dialysis catheters. AB - BACKGROUND: Continuous ambulatory peritoneal dialysis (CAPD) catheters provide a preferred alternative to hemodialysis in a growing population with chronic kidney disease. However, CAPD catheters traditionally have been associated with a high rate of nonfunction with both open and laparoscopic procedures. New advanced laparoscopic techniques using rectus sheath tunneling and omentopexy have been reported to improve catheter function. STUDY DESIGN: This study retrospectively reports the Cleveland Clinic experience during the transition from basic to advanced laparoscopic techniques from June 2002 to July 2008. A total of 197 patients were identified: 68 who underwent insertion with basic techniques and 129 who received catheters with advanced techniques. Primary nonfunction, procedural complications, and overall nonfunction rate were analyzed using the most recent follow-up to June 2008. RESULTS: Primary nonfunction occurred in 25 of 68 (36.7%) patients in the basic group; this occurred in only 6 of 129 patients (4.6%) in the advanced group (p < 0.0001). The overall rate of complications including nonfunction from primary and secondary sources, peritoneal leak, peritonitis, port-site hernia, and bleeding occurred in 31 of 68 (45.6%) patients in the basic group and 21 of 129 (16.28%) patients in the advanced group (p < 0.0001). CONCLUSIONS: These data clearly show a significant improvement in CAPD catheter function using omentopexy and rectus sheath tunneling. These advanced laparoscopic techniques should become the preferred method of CAPD catheter insertion. PMID- 21036074 TI - Overlap method: novel intracorporeal esophagojejunostomy after laparoscopic total gastrectomy. PMID- 21036075 TI - Taking disclosure seriously: disclosing financial conflicts of interest at the American College of Surgeons. AB - BACKGROUND: The accurate disclosure of financial conflicts of interest has come to light as a sound component of managing relationships between surgeons and industry. STUDY DESIGN: In this study, we summarize and categorize 4 years of disclosures (2006-2009) given by presenters at the Annual Clinical Congress of the American College of Surgeons. RESULTS: We report 3,122 disclosures by 480 individuals. "Colorectal surgeon" was the most common profession among disclosers. The most common type of disclosure was "consulting." The company with the highest number of disclosures was Covidien. Disclosers used 195 different terms to describe their relationships. CONCLUSIONS: We propose a standard nomenclature for use by surgeons when disclosing future conflicts of interest. As the attention to disclosures increases, sound policy decisions would be facilitated by such a standardized nomenclature system. PMID- 21036076 TI - American College of Surgeons National Surgical Quality Improvement Program Pediatric: a phase 1 report. AB - BACKGROUND: There has been a long-standing desire to implement a multi institutional, multispecialty program to address surgical quality improvement for children. This report documents results of the initial phase of the American College of Surgeons National Surgical Quality Improvement Program Pediatric. STUDY DESIGN: From October 2008 to December 2009, patients from 4 pediatric referral centers were sampled using American College of Surgeons National Surgical Quality Improvement Program methodology tailored to children. RESULTS: A total of 7,287 patients were sampled, representing general/thoracic surgery (n = 2,237; 30.7%), otolaryngology (n = 1,687; 23.2%), orthopaedic surgery (n = 1,367; 18.8%), urology (n = 893; 12.3%), neurosurgery (n = 697; 9.6%), and plastic surgery (n = 406; 5.6%). Overall mortality rate detected was 0.3% and 287 (3.9%) patients had postoperative occurrences. After accounting for demographic, preoperative, and operative factors, occurrences were 4 times more likely in those undergoing inpatient versus outpatient procedures (odds ratio [OR] = 4.71; 95% CI, 3.01-7.35). Other factors associated with higher likelihood of postoperative occurrences included nutritional/immune history, such as preoperative weight loss/chronic steroid use (OR = 1.49; 95% CI, 1.03-2.15), as well as physiologic compromise, such as sepsis/inotrope use before surgery (OR = 1.68; 95% CI, 1.10-1.95). Operative factors associated with occurrences included multiple procedures under the same anesthetic (OR = 1.58; 95% CI, 1.21-2.06) and American Society of Anesthesiologists classification category 4/5 versus 1 (OR = 5.74; 95% CI, 2.94-11.24). Specialty complication rates varied from 1.5% for otolaryngology to 9.0% for neurosurgery (p < 0.001), with specific procedural groupings within each specialty accounting for the majority of complications. Although infectious complications were the predominant outcomes identified across all specialties, distribution of complications varied by specialty. CONCLUSIONS: Based on this initial phase of development, the highly anticipated American College of Surgeons National Surgical Quality Improvement Program Pediatric has the potential to identify outcomes of children's surgical care that can be targeted for quality improvement efforts. PMID- 21036078 TI - Advances in the understanding of pathogenesis, and diagnostics and therapeutics for feline allergic asthma. AB - Asthma is a common inflammatory disease of the lower airways and is believed to be of allergic etiology in cats. As little progress has been made in establishing rigorous criteria to differentiate it from other inflammatory lower airway diseases such as chronic bronchitis, descriptions of 'asthma' in the literature have often been inaccurate, grouping this syndrome with other feline airway diseases. With the development of more sensitive and specific diagnostics, it will become easier to distinguish asthma as a disease entity. Pulmonary function testing with bronchoprovocation/bronchodilator responsiveness trials and biomarkers hold particular promise. Discrimination is of critical importance as targeted therapies for the allergic inflammatory cascade are developed and become available for therapeutic trials in pet cats. PMID- 21036077 TI - Impact of childhood inguinal hernia repair in adulthood: 50 years of follow-up. AB - BACKGROUND: Short-term follow-up of pediatric inguinal herniorrhaphies has yielded low morbidity and recurrence rates. Nonetheless, the impact of childhood inguinal herniorrhaphy on the adulthood risk for repeat groin operation, chronic groin pain, and infertility has not been established. STUDY DESIGN: A survey was mailed to all patients who underwent a primary inguinal hernia repair as a child at our institution from 1956 to 1960. The survey inquired about repeat groin operation, chronic groin pain, and fertility status. Demographic and operative information from respondents was obtained from medical record review. RESULTS: Of 332 eligible patients, 213 (66%) responded to the survey, accounting for 252 inguinal herniorrhaphies (174 unilateral, 33 bilateral, and 6 sequential contralateral). All hernias were indirect, more common on the right (right, 49%; left, 25%; bilateral, 26%), with males predominating (91%). History of premature birth was present in 5 (2%) patients. High ligation of the hernia sac was performed in 90% of the repairs. Hydrocelectomy was performed in 25 (13%) and orchidopexy in 37 (19%) patients. With a median follow-up of 49 years (range 47.2 to 52.1 years), a total of 21 (8.4%) repeat and 13 (6%) contralateral groin operations were observed. Chronic groin pain and a medical diagnosis of infertility were reported by 7 (3%) and 10 (5%) patients, respectively. CONCLUSIONS: Childhood inguinal hernia repairs do not appear to decrease or increase the risk of inguinal hernia development in adulthood. Parents and children undergoing a childhood inguinal hernia repair should be informed that although the risk for a true indirect hernia recurrence is low, the risk of repeat groin operation (8.4%) and chronic groin pain (3%) remain present in adulthood. PMID- 21036079 TI - Chemical restraint and anaesthetic effects of a tiletamine zolazepam/ketamine/detomidine combination in cattle. AB - The immobilisation and anaesthesia of free-ranging cattle requires the administration of appropriate drugs in small volume via rifle or dart. The objective of this randomised controlled study was to test the capacity of a concentrated combination of tiletamine-zolazepam (TZ), ketamine (K) and detomidine (D) (TZKD) to immobilise/anaesthetise calves. Following administration of low, medium and high doses of TZKD to six healthy animals IM, the time-of onset and duration of anaesthesia were recorded, in addition to standard cardio respiratory parameters. Two noxious stimuli were applied to assess the analgesic effect of the combination. TZKD produced a dose-dependent anaesthetic action associated with respiratory depression and moderate hypoxaemia. Total recumbency lasted from 1h (with low dose) to 2h (with medium and high doses). The findings indicate that TZKD induces anaesthesia in calves, suitable not only for animal immobilisation, but also to carry out minor surgical procedures with or without additional local analgesia. Respiratory depression was the most severe side effect and careful patient monitoring is recommended when using this drug combination. PMID- 21036080 TI - Identification of immunodominant antigens of Mycobacterium bovis by expression library immunization. AB - This study combines two methodologies - vector expression of a genomic library and proteomics - to identify immunogenic proteins of Mycobacterium bovis. Immunization of BALB/c mice with a plasmid DNA pool from the library, containing approximately 8000 clones, induced a humoral response that facilitated the detection of 12 antigenic proteins by Western blotting. Two-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and mass spectrometry identified four proteins (Cpn60-1, HSP70, EF-Tu, and AdoHcyase). Such genomic immunization offers the possibility of in vivo screening of potential candidate M. bovis antigens. PMID- 21036081 TI - Reduction of spin diffusion artifacts from 2D zfr-INADEQUATE MAS NMR spectra. AB - The primary shortcoming of the z-filtered refocused INADEQUATE MAS NMR pulse sequence is the possibility of artifacts introduced during the z-filter due to spin diffusion where by extra peaks in the single-quantum dimension (from other sites in the molecule) appear correlated with a given double-quantum frequency. This is a problem when the spinning speeds are too slow (less than 15 kHz) to sufficiently average the proton-proton homonuclear dipolar couplings. This would be especially important when working with large volume rotors that are difficult to spin fast enough to completely average the homonuclear couplings. In our experiments we used the frequency-switched Lee-Goldberg (FSLG) method of homonuclear decoupling during the z-filter to remove the artifact peaks. This method has the advantage of being quite easy to setup and implement on most modern NMR spectrometers. PMID- 21036082 TI - Lipomatous variant of myofibroblastoma with epithelioid features: a rare and diagnostically challenging breast lesion. AB - Myofibroblastoma of the breast is an unusual benign spindle cell tumor composed of cells with histologic, immunohistochemical, and ultrastructural features of myofibroblasts. In addition to the classic form, a few variants of myofibroblastoma have been described. Recognition of these variants is important to prevent overdiagnosis of a malignant lesion, especially on core biopsy. Three variants that can cause particular confusion on core biopsy are the lipomatous, infiltrative, and epithelioid variants of myofibroblastoma. Thus far, there have been only a few reports of these variants in the English literature. We report a rare case of a lipomatous variant of myofibroblastoma with an epithelioid cell component and discuss the differential diagnosis and potential diagnostic pitfalls. PMID- 21036083 TI - Theoretical study on the electronic absorption spectra and molecular orbitals of ten novel ruthenium sensitizers derived from N3 and K8. AB - Ten novel sensitizer candidates Ru2, Ru4, Ru5, Ru6, Ru7, Ru8, Ru9, Ru10, Ru11 and Ru12 derived from the sensitizers N3 and K8 were designed and studied using the density functional theory and time-dependent density functional theory calculations. The influences of the C=C double bonds between the carboxyl groups and the bipyridine ring as well as the numbers and positions of the -CN groups adjacent to the carboxyl groups on the properties of the sensitizer candidates were discussed. The energy levels and the spatial distributions of the frontier molecular orbitals as well as the electronic absorption spectra of these complexes were compared with those of N3 and K8. Ru10 and Ru7 were found promising to provide superior photon-to-current conversion efficiency to those of N3 and K8 in ruthenium complex sensitized solar cells. PMID- 21036084 TI - Molecular insight into the specific binding of ADP-ribose to the nsP3 macro domains of chikungunya and Venezuelan equine encephalitis viruses: molecular dynamics simulations and free energy calculations. AB - The outbreaks of chikungunya (CHIKV) and venezuelan equine encephalitis (VEEV) viral infections in humans have emerged or re-emerged in various countries of "Africa and southeast Asia", and "central and south America", respectively. At present, no drug or vaccine is available for the treatment and therapy of both viral infections, but the non-structural protein, nsP3, is a potential target for the design of potent inhibitors that fit at the adenosine-binding site of its macro domain. Here, so as to understand the fundamental basis of the particular interactions between the ADP-ribose bound to the nsP3 amino acid residues at the binding site, molecular dynamics simulations were applied. The results show that these two nsP3 domains share a similar binding pattern for accommodating the ADP ribose. The ADP-ribose phosphate unit showed the highest degree of stabilization through hydrogen bond interactions with the nsP3 V33 residue and the consequent amino acid residues 110-114. The adenine base of ADP-ribose was specifically recognized by the conserved nsP3 residue D10. Additionally, the ribose and the diphosphate units were found to play more important roles in the CHIKV nsP3-ADP ribose complex, while the ter-ribose was more important in the VEEV complex. The slightly higher binding affinity of ADP-ribose toward the nsP3 macro domain of VEEV, as predicted by the simulation results, is in good agreement with previous experimental data. These simulation results provide useful information to further assist in drug design and development for these two important viruses. PMID- 21036085 TI - Computational and mutagenesis studies of the streptavidin native dimer interface. AB - Wt streptavidin forms a domain swapped tetramer consisting of two native dimers. The role of tetramerization has been studied previously and is known to contribute to biotin binding by allowing the exchange of W120 between adjacent subunits. However, the role of dimer formation in streptavidin folding and function has been largely overlooked to date, although native dimers are necessary for tetramer formation and thus for high affinity biotin binding. To understand how the side chain interactions at the dimer interface stabilize the subunit association, we studied the structural and functional consequences of introducing interfacial mutations by a combination of molecular dynamics (MD) simulation and biochemical characterization. In particular, we introduced rational mutations at the dimer interface to engineer new side chain interactions and measured the stability and function of the resulting mutants. We focused on two residues that form a "knob" and a "hole" pair, G74 and T76, since steric complementarity plays an important role at these positions. We introduced mutations that would change the polarity and side chain packing to test if the interface can be rationally redesigned. Both energy calculation and geometric parameterization were used to interpret the simulated structures and predict how the mutations affect the dimer stability. In this regard, obtaining precise energy estimates was difficult because the simulated structures have large stochastic variations and some mutants did not reach an equilibrium by the end of the simulation. In contrast, comparing the wt and mutants to one another and parameterizing the simulation using a geometric parameter, i.e. the degree of solvation of the buried interface, resulted in a testable prediction regarding which mutations would result in a stable dimer. We present experimental data (denaturation and binding measurements) to show that an intuitive parameter based on physical reasoning can be useful for characterizing simulations that are difficult to analyze quantitatively. PMID- 21036086 TI - Molecular characterization of a new deletion of the GBA1 gene due to an inter Alu recombination event. AB - Gaucher disease is the most frequent lysosomal storage disorder due to the autosomal recessive deficiency of acid beta-glucosidase. More than 300 mutations in the GBA1 gene have been described. However only one large deletion of the GBA1 gene has been reported to date. Here, using a combination of different experimental approaches including PCR, sequencing and Southern blot analysis, we describe the identification and characterization of a new large deletion of the GBA1 gene due to an inter Alu recombination event. PMID- 21036087 TI - Myeloma-related disorder with leukaemic progression in a cat. AB - A 10-year-old American Shorthair cat with nasal discharge, anorexia, and weight loss was found to have pancytopenia and hyperproteinaemia. Bone marrow aspiration revealed atypical plasma cells that totalled 50% of the nucleated bone marrow cells. The number of atypical plasma cells progressively increased in the peripheral blood during the observation period of 64 days. The cat did not respond to treatments with melphalan, chlorambucil, and prednisolone, and died 71 days after the initial presentation. Clinical, cytological, histopathological, and immunohistochemical findings in this case supported the diagnosis of myeloma related disorder (MRD) with leukaemic progression. PMID- 21036088 TI - NT-proBNP measurement fails to reliably identify subclinical hypertrophic cardiomyopathy in Maine Coon cats. AB - The purpose of this study was to evaluate the value of measuring plasma NT-proBNP concentration as a screening tool in cats with varying severity of subclinical hypertrophic cardiomyopathy (HCM). Plasma NT-proBNP concentration was measured in 35 cats that had previously been classified as normal, equivocal, moderate HCM or severe HCM via echocardiography. No cat had ever been in congestive heart failure. Cats with severe HCM had a significantly higher NT-proBNP concentration compared to the other groups (P<0.0003), however, the sensitivity of NT-proBNP for diagnosing cats with severe disease was only 44% (cutoff<=100pmol/l) to 55% (cutoff<=40pmol/l). There was no significant difference in NT-proBNP concentration between normal, equivocal and moderate categories (sensitivity for detecting moderate HCM was 0%). Based on the results of this study, NT-proBNP concentration is not considered adequate as a screening test for detecting mild to moderate HCM in Maine Coon cats and it appears that it may miss many cats with severe HCM. PMID- 21036089 TI - Prevalence of feline leukaemia provirus DNA in feline lymphomas. AB - A significant drop in the prevalence of feline leukaemia virus (FeLV) antigenaemic cats and antigen-associated lymphomas has been observed after the introduction of FeLV vaccination and antigen-testing with removal of persistently antigenaemic cats. However, recent reports have indicated that regressively infected cats may contain FeLV provirus DNA and that lymphoma development may be associated with the presence of provirus alone. In the present study, we investigated the presence of FeLV antigen and provirus DNA in 50 lymphomas by immunohistochemistry and semi-nested polymerase chain reaction, respectively. Interestingly, almost 80% of T-cell lymphomas and 60% of B-cell lymphomas contained provirus DNA while only 21% of T-cell lymphomas and 11% of B-cell lymphomas expressed FeLV antigen. In conclusion, our results support previous hypotheses that vaccination and removal of persistently antigenaemic cats have led to a drop in FeLV antigen-expressing lymphomas. However, FeLV provirus DNA is still present in a high percentage of feline lymphomas. PMID- 21036090 TI - The seasonality of pandemic and non-pandemic influenzas: the roles of solar radiation and vitamin D. AB - OBJECTIVES: Seasonal variations in ultraviolet B (UVB) radiation cause seasonal variations in vitamin D status. This may influence immune responses and play a role in the seasonality of influenza. METHODS: Pandemic and non-pandemic influenzas in Sweden, Norway, the USA, Singapore, and Japan were studied. Weekly/monthly influenza incidence and death rates were evaluated in view of monthly UVB fluences. RESULTS: Non-pandemic influenzas mostly occur in the winter season in temperate regions. UVB calculations show that at high latitudes very little, if any, vitamin D is produced in the skin during the winter. Even at 26 degrees N (Okinawa) there is about four times more UVB during the summer than during the winter. In tropical regions there are two minor peaks in vitamin D photosynthesis, and practically no seasonality of influenza. Pandemics may start with a wave in an arbitrary season, while secondary waves often occur the following winter. Thus, it appears that a low vitamin D status may play a significant role in most influenzas. CONCLUSIONS: In temperate latitudes even pandemic influenzas often show a clear seasonality. The data support the hypothesis that high fluences of UVB radiation (vitamin D level), as occur in the summer, act in a protective manner with respect to influenza. PMID- 21036091 TI - Aspergillus endocarditis: a review of the literature. AB - We present a case of cardiac device-related Aspergillus endocarditis in a patient with a pacemaker and an allogeneic bone marrow transplant to segue into a review of the Aspergillus endocarditis literature. Aspergillus endocarditis should be suspected in patients with underlying immunosuppression, negative cultures, and a vegetation on echocardiography. Diagnosis ultimately requires confirmation by tissue histology and culture. The optimal treatment approach often requires aggressive surgical debridement in conjunction with prolonged antifungal therapy. PMID- 21036092 TI - Cavitational chemistry: a mild and efficient multi-component synthesis of amidoalkyl-2-naphthols using reusable silica chloride as catalyst under sonic conditions. AB - An efficient and direct procedure for the synthesis of amidoalkyl-2-naphthol derivatives has been described. The process employs a three-component cyclocondensation reaction in one-pot using beta-naphthol, aromatic aldehyde and acetamide or benzamide in the presence of silica chloride accelerated by ultrasound giving the product in excellent yield in very short duration. PMID- 21036093 TI - Video game-based neuromuscular electrical stimulation system for calf muscle training: a case study. AB - A video game-based training system was designed to integrate neuromuscular electrical stimulation (NMES) and visual feedback as a means to improve strength and endurance of the lower leg muscles, and to increase the range of motion (ROM) of the ankle joints. The system allowed the participants to perform isotonic concentric and isometric contractions in both the plantarflexors and dorsiflexors using NMES. In the proposed system, the contractions were performed against exterior resistance, and the angle of the ankle joints was used as the control input to the video game. To test the practicality of the proposed system, an individual with chronic complete spinal cord injury (SCI) participated in the study. The system provided a progressive overload for the trained muscles, which is a prerequisite for successful muscle training. The participant indicated that he enjoyed the video game-based training and that he would like to continue the treatment. The results show that the training resulted in a significant improvement of the strength and endurance of the paralyzed lower leg muscles, and in an increased ROM of the ankle joints. Video game-based training programs might be effective in motivating participants to train more frequently and adhere to otherwise tedious training protocols. It is expected that such training will not only improve the properties of their muscles but also decrease the severity and frequency of secondary complications that result from SCI. PMID- 21036094 TI - Automated quantitative microstructural analysis of metastatically involved vertebrae: effects of stereologic model and spatial resolution. AB - SUMMARY OF BACKGROUND DATA: Preclinical models of spinal metastases allow for the application of micro-image based structural assessments, however, large data sets resulting from high resolution scanning motivate a need for robust automated analysis tools. Accurate assessment of changes in vertebral architecture, however, may depend both on the resolution of images acquired and the models used to represent the structural data. OBJECTIVE: To apply a recently developed automated MUCT based analysis tool to quantify the effect of diffuse metastatic disease on rat vertebral architecture at multiple resolutions. It was hypothesized that automated methods could accurately quantify differences in vertebral microstructure and that diffuse metastatic disease could be shown to have significant negative architectural effects on trabecular bone independent of stereologic model and resolution. METHODS: MUCT images acquired at 14 MUm(3) of healthy and metastatically involved whole lumbar rat vertebrae were analyzed at high, medium and low (8.725, 17.45, and 34.9 MUm(3)) resolutions using an automated algorithm to yield micro-structural measures of the trabecular centrum and cortical shell. The images analyzed at different resolutions were obtained via up/downsampling of the acquired image data. Trabecular thickness was evaluated with the Parfitt and Hildebrand models, and anisotropy was evaluated through calculation of mean intercept length. RESULTS: Significant differences in microstructural parameters measured in comparing healthy and metastatically involved vertebrae were affected by resolution, however, relative anisotropy was maintained. The Parfitt and Hilderbrand models yielded similar structural differences between healthy and metastatic vertebrae, however, the Hildebrand model was limited due to segmentation accuracy required for its automated application. CONCLUSIONS: Differences in microstructural parameters generated through automated analysis at high resolution suggest that diffuse MT1 osteolytic destruction in whole rat vertebrae results primarily in loss of trabeculae in the metastatic vertebrae, as opposed to trabecular thinning. The sensitivity of the bony architectural parameters to resolution motivates the need for high resolution scanning or post-processing of images. PMID- 21036095 TI - Multi-scale interaction of particulate flow and the artery wall. AB - We discuss, from the perspective of basic science, the physical and biological processes which underlie atherosclerotic (plaque) initiation at the vascular endothelium, identifying the widely separated spatial and temporal scales which participate. We draw on current, related models of vessel wall evolution, paying particular attention to the role of particulate flow (blood is not a continuum fluid), and proceed to propose, then validate all the key components in a multiply-coupled, multi-scale modeling strategy (in qualitative terms only, note). Eventually, this strategy should lead to a quantitative, patient-specific understanding of the coupling between particulate flow and the endothelial state. PMID- 21036096 TI - Mechanics and computational simulation of blood flow in microvessels. AB - Blood is a concentrated suspension of red blood cells (RBCs). Motion and deformation of RBCs can be analyzed based on knowledge of their mechanical characteristics. Axisymmetric models for single-file motion of RBCs in capillaries yield predictions of apparent viscosity in good agreement with experimental results for diameters up to about 8 MUm. Two-dimensional simulations, in which each RBC is represented as a set of interconnected viscoelastic elements, predict that off-centre RBCs in an 8-MUm channel take asymmetric shapes and drift toward the centre-line. Predicted trajectories agree with observations in microvessels of the rat mesentery. An isolated RBC initially positioned near the wall of a 20-MUm channel is deformed into an asymmetric shape, migrates away from the wall, and then enters a complex tumbling motion with continuous shape change. Realistic simulation of multiple interacting RBCs in microvessels remains as a major challenge. PMID- 21036097 TI - Computer assisted reconstruction of complex proximal humerus fractures for preoperative planning. AB - Operative treatment of displaced fractures of the proximal humerus is among the most difficult problems in orthopedic shoulder surgery. An accurate preoperative assessment of fragment displacement is crucial for a successful joint restoration. We present a computer assisted approach to precisely quantify these displacements. The bone is virtually reconstructed by multi-fragment alignment. In case of largely displaced pieces, a reconstruction template based on the contralateral humerus is incorporated in the algorithm to determine the optimal assembly. Cadaver experiments were carried out to evaluate our approach. All cases could be successfully reconstructed with little user interaction, and only requiring a few minutes of processing time. On average, the reassembled bone geometries resulted in a translational displacement error of 1.3+/-0.4 mm and a rotational error of 3.4+/-2.2 degrees , respectively. PMID- 21036098 TI - Mechanisms controlling pathogen colonization of the gut. AB - The intestinal microbiota can protect efficiently against colonization by many enteric pathogens ('colonization resistance', CR). This phenomenon has been known for decades, but the mechanistic basis of CR is incompletely defined. At least three mechanisms seem to contribute, that is direct inhibition of pathogen growth by microbiota-derived substances, nutrient depletion by microbiota growth and microbiota-induced stimulation of innate and adaptive immune responses. In spite of CR, intestinal infections are well known to occur. In these cases, the multi faceted interactions between the microbiota, the host and the pathogen are shifted in favor of the pathogen. We are discussing recent progress in deciphering the underlying molecular mechanisms in health and disease. PMID- 21036099 TI - Establishing an unusual cell type: how to make a dikaryon. AB - The dikaryons of basidiomycete fungi represent an unusual cell type required for complete sexual development. Dikaryon formation occurs via the activities of cell type-specific homeodomain transcription factors, which form regulatory complexes to establish the dikaryotic state. Decades of classical genetic and cell biological studies in mushrooms have provided a foundation for more recent molecular studies in the pathogenic species Ustilago maydis and Cryptococcus neoformans. Studies in these systems have revealed novel mechanisms of regulation that function downstream of classic homeodomain complexes to ensure that dikaryons are established and propagated. Comparisons of these dikaryon-specific networks promise to reveal the nature of regulatory network evolution and the adaptations responsible for driving complex eukaryotic development. PMID- 21036100 TI - Visible luminescence of dysprosium ions in oxyhalide lead borate glasses. AB - Visible luminescence of Dy(3+) ions in oxyhalide lead borate glasses was examined. Luminescence spectra show two intense bands at 480 nm and 573 nm due to (4)F(9/2)->(6)H(15/2) (blue) and (4)F(9/2)->(6)H(13/2) (yellow) transitions of Dy(3+). Luminescence decays from (4)F(9/2) state and yellow-to-blue luminescence intensity ratios (Y/B) were analysed with PbX(2) (X=F, Cl) content. An introduction of PbX(2) to the borate glass results in the increasing of (4)F(9/2) lifetime and the decreasing of yellow-to-blue luminescence intensity ratio, which is due to reduction of covalency between Dy(3+) and O(2-)/X(-) ions. PMID- 21036101 TI - Intramolecular charge delocalization and nonlinear optical properties of push pull chromophore 1-(4-N,N-dimethylaminopyridinium) acetic acid bromide monohydrate from vibrational spectra. AB - FT-Raman and FT-IR spectra of the nonlinear optical crystal 1-(4-N,N dimethylaminopyridinium) acetic acid bromide monohydrate have been recorded and analyzed. The equilibrium geometry, vibrational wavenumbers and the first order hyperpolarizability of the crystal have been calculated with the help of density functional theory computations. The assignments of the vibrational spectra have been carried out with the help of Scaled Quantum Mechanic force field theory. Optimized geometry gives the charge transfer interaction of the pyridine ring and the amino group in the electron-donor side of the nonlinear optic chromophore. Electron-phonon coupling and O-H?O interactions in making the molecule nonlinear optical active have been analyzed based on the vibrational spectral features. The Natural Bond Orbital analysis confirms the occurrence of strong intermolecular O H?O hydrogen bonding. PMID- 21036102 TI - Seizure induced by sub-threshold 10-Hz rTMS in a patient with multiple risk factors. PMID- 21036103 TI - Roles of spvB and spvC in S. Typhimurium colitis via the alternative pathway. AB - Salmonella enterica subspecies I serovar Typhimurium (S. Typhimurium) is a frequent cause of diarrhea worldwide. It employs 2 type III secretion systems (TTSS) to elicit mucosal inflammation via the TTSS-1-dependent 'classical' or the TTSS-2-dependent 'alternative' pathway. If TTSS-1 is defective (in invG or invC mutants), the pathogen is confined to the alternative pathway; transits the epithelium in a dendritic cell-dependent fashion, relocalizes from CD11c(+) dendritic cells to CD11c(-) cells, and elicits inflammation by day 3 post infection (p.i.). It has remained unclear whether other virulence factors may also contribute to this process. Here, we used the streptomycin mouse model to analyze whether spvB and spvC, virulence factors known to affect the pathogen phagocyte interaction at systemic sites, might contribute to triggering colitis. By 12h p.i., spvBC mutants elicited wild-type levels of gut inflammation and mucosal cytokine induction via the classical pathway. However, spvBC mutants confined to the alternative pathway triggered reduced levels of gut inflammation by day 3 p.i. (S. tm(DeltainvGDeltaspvBC) vs. S. tm(DeltainvG)). Detailed analyses using spvB or spvC mutants (e.g. S. tm(DeltainvCDeltaspvB)) revealed that spvB was required for efficient lamina propria colonization and suggested that this was attributable to defective relocalization from dendritic- to CD11c( ) cells. This establishes a novel virulence phenotype for spvB in the alternative pathway of S. Typhimurium colitis. PMID- 21036104 TI - Unraveling the intricacies of receptor activated cell signaling and transcriptional cascades enhance opportunities to develop new therapeutic targets for endocrine and metabolic diseases. PMID- 21036105 TI - Resolution of hyperlipidemia follows surgical weight loss in patients undergoing Roux-en-Y gastric bypass surgery: a 6-year analysis of data. AB - BACKGROUND: Hyperlipidemia is a known risk factor for the development of atherosclerosis and coronary artery disease in morbidly obese individuals. The aim of our study was to review the trends in the serum lipid profiles of patients undergoing Roux-en-Y gastric bypass at our institution. METHODS: A retrospective 6-year analysis of data of patients undergoing Roux-en-Y gastric bypass was performed. The indicators of resolution of hyperlipidemia were reviewed for 6 months and then annually for 6 consecutive years. Hyperlipidemia was defined according to the American Heart Association and National Cholesterol Education Program Adult Treatment Panel III guidelines. The changes in the lipid profile of the patients with subnormal levels of high-density lipoprotein (HDL) cholesterol and total cholesterol/HDL cholesterol risk ratio were also examined. RESULTS: A total of 94 patients were diagnosed with hyperlipidemia, of whom 23 were receiving clinical treatment. The mean patient age was 39 +/- 9 years, and the mean body mass index was 50 +/- 9.6 kg/m(2), with a female predominance. The mean baseline serum levels were as follows: total cholesterol 220 +/- 42.2 mg/dL, triglycerides 212 +/- 123.5 mg/dL, low-density lipoprotein cholesterol 135 +/- 34.2 mg/dL, and HDL cholesterol 51 +/- 12 mg/dL. The optimization of serum total cholesterol, triglycerides, and low-density lipoprotein cholesterol profiles was seen in all patients within 6 months after surgery. The HDL cholesterol levels improved more slowly, reaching desirable levels within 12 months after surgery. All patients taking lipid-lowering agents no longer required the medication at the end of the study period. CONCLUSION: Roux-en-Y gastric bypass provides an effective remission of hyperlipidemia in morbidly obese patients, with most patients no longer requiring lipid-lowering agents within 6 months after surgery. The improvement in overall lipid profiles continued during follow-up after surgery. PMID- 21036106 TI - Visfatin levels in female, morbid, nondiabetic obese patients after biliopancreatic diversion surgery. AB - BACKGROUND: Visfatin was recently identified as a protein preferentially expressed in visceral adipose tissue. The purpose of the present study was to investigate the changes in serum visfatin levels after biliopancreatic diversion and the association of the changes observed with other parameters in morbidly nondiabetic obese women. METHODS: A sample of 27 morbidly obese women (body mass index >40 kg/m(2)) were operated. The biochemical and anthropometric parameters were measured at the initial visit and 1 year after surgery. The frequency of patients with hypertension and hyperlipidemia was recorded at 1 year. RESULTS: The mean patient age was 46.0 +/- 13.0 years, and the mean preoperative body mass index was 46.3 +/- 13.1 kg/m(2). The body mass index, weight, waist circumference, fat mass, blood pressure, total cholesterol, and low-density lipoprotein cholesterol had decreased significantly. The visfatin levels did not change after surgery (5.70 +/- 1.84 ng/mL versus 6.12 +/- 1.68 ng/mL; P = NS). The correlation analysis showed a positive association between the baseline visfatin and total cholesterol level (r = 0.49; P <.01). CONCLUSION: The massive weight reduction 1 year after biliopancreatic diversion was not associated with a significant change in the circulating visfatin levels in morbidly obese women. PMID- 21036107 TI - Is there a gender disparity in treatment of coronary artery disease? PMID- 21036108 TI - The Impella ventricular assist device: use in patients at high risk for coronary interventions: successful multivessel percutaneous coronary intervention in a 62 year-old high-risk patient. AB - The Impella Recover LP 2.5 (Abiomed, Danvers, MA, USA) is a ventricular assist device that is easily placed and has low adverse events. It helps unload myocardial demand and enables revascularization in patients who are otherwise at extreme risk for percutaneous coronary intervention (PCI). It breaks the cycle of cardiogenic shock and is indicated in patients with low ejection fraction (EF), acute heart failure, and concurrent high-risk factors for intervention or surgery. Many case reports have been published regarding use of this device in high-risk PCIs, but successful intervention in two high-risk vessels in one setting has rarely been reported. We describe such a case report here where two critical lesions in LAD and circumflex arteries were successfully intervened on with the assistance of this device. PMID- 21036109 TI - Currently available methods for platelet function analysis: advantages and disadvantages. AB - Platelets play a pivotal role in normal hemostasis, and derangement of their function can lead to hemorrhage or thrombosis. While progress has been made in elucidating the molecular mechanisms leading to platelet adhesion, aggregation, shape change and secretion, clinically useful tests of platelet function have lagged. A number of dedicated platelet function instruments that are much simpler to use and are now utilized as point-of-care (POC) instruments have now become available. Some instruments have been incorporated into routine clinical use and can be utilized not only as general screening tests of platelet function but as monitors of antiplatelet therapy and to potentially assess both risk of bleeding and/or thrombosis. Some of the factors that differentiate these tests are sample volume requirements, the use of whole blood, the presence of shear, POC status, need for a technician and expense. The following is a review of some of the commonly used tests of platelet function, along with their advantages and disadvantages. The tests and pertinent instruments described are based on aggregation, shear stress platelet contribution to clot strength, flow cytometry and serum and urinary thromboxane metabolites. PMID- 21036110 TI - The effect of smoking nicotine tobacco versus smoking deprivation on motion sickness. AB - BACKGROUND: The experienced smoker maintains adequate nicotine levels by 'puff-by puff self-control' which also avoids symptomatic nauseating effects of nicotine overdose. It is postulated that there is a varying 'dynamic threshold for nausea' into which motion sickness susceptibility provides an objective toxin-free probe. Hypotheses were that: (i) nicotine promotes motion sickness whereas deprivation protects; and (ii) pleasurable effects of nicotine protect against motion sickness whereas adverse effects of withdrawal have the opposite effect. METHODS: Twenty-six healthy habitual cigarette smokers (mean +/- SD) 15.3 +/- 7.6 cigs/day, were exposed to a provocative cross-coupled (coriolis) motion on a turntable, with sequences of 8 head movements every 30s. This continued to the point of moderate nausea. Subjects were tested after either ad-lib normal smoking (SMOKE) or after overnight deprivation (DEPRIV), according to a repeated measures design counter-balanced for order with 1-week interval between tests. RESULTS: Deprivation from recent smoking was confirmed by objective measures: exhaled carbon monoxide CO was lower (P<0.001) for DEPRIV (8.5 +/- 5.6 ppm) versus SMOKE (16.0 +/- 6.3 ppm); resting heart rate was lower (P<0.001) for DEPRIV (67.9 +/- 8.4 bpm) versus SMOKE (74.3 +/- 9.5 bpm). Mean +/- SD sequences of head movements tolerated to achieve moderate nausea were more (P = 0.014) for DEPRIV (21.3 +/- 9.9) versus SMOKE (18.3 +/- 8.5). DISCUSSION: Tolerance to motion sickness was aided by short-term smoking deprivation, supporting Hypothesis (i) but not Hypothesis (ii). The effect was was approximately equivalent to half of the effect of an anti-motion sickness drug. Temporary nicotine withdrawal peri operatively may explain why smokers have reduced risk for postoperative nausea and vomiting (PONV). PMID- 21036111 TI - Enantiomeric composition analysis of pranoprofen in equine plasma and urine by chiral liquid chromatography-tandem mass spectrometry in selected reaction monitoring mode. AB - The enantioseparation of pranoprofen after its addition in racemic form into equine plasma and urine was conducted by chiral liquid chromatography-tandem mass spectrometry in selected reaction monitoring mode. The methods for the assay of both enantiomers were linear (r>=0.9943) in the low range from 0.001 to 0.1MUg/mL and high range from 0.01 to 1.0MUg/mL with good precision (% RSD<=5.6) and accuracy (% RE=-5.3 to 1.9). When racemic pranoprofen was orally administered to four horses at a single dose of 3.1mg/kg, the median plasma concentrations of (R) pranoprofen were lower than the levels of (S)-pranoprofen from start to finish. In contrast, the urinary level of (R)-pranoprofen was 2.5 fold higher than (S) pranoprofen level for the first 6h, followed by its rapid decrease down below (S) pranoprofen concentration. Monitoring of the R/S ratios in equine urine may be useful for the prevention of false positive in horse doping test. PMID- 21036112 TI - Anthropometry of love: height and gender asymmetries in interethnic marriages. AB - Both in the UK and in the US, we observe puzzling gender asymmetries in the propensity to outmarry: Black men are more likely to have white spouses than Black women, but the opposite is true for Chinese: Chinese men are half less likely to be married to a White person than Chinese women. We argue that differences in height distributions, combined with a simple preference for the husband to be taller than the wife, can help explain these ethnic-specific gender asymmetries. Blacks are taller than Asians, and we argue that this significantly affects their marriage prospects with whites. We provide empirical support for this hypothesis using data from the Millennium Cohort Study. Specifically, we find that ethnic differences in propensity to intermarry with Whites shrink when we control for the proportion of suitable partners with respect to height. PMID- 21036113 TI - [Risk factors involved in the need for blood transfusion in very low birth weight newborns treated with erythropoietin]. AB - OBJECTIVE: To identify and quantify risk factors related to red blood cell transfusion in premature babies weighing<1,500g who received erythropoietin (EPO). Secondly, to assess the relationship between retinopathy of prematurity and rh-EPO. MATERIAL AND METHODS: Prospective descriptive study of infants admitted to the Reina Sofia University Hospital between January 2006 and March 2009. Infants reviewed had a birth weight<1,500g and gestational age<32 weeks. Infants were administered rh-EPO 750IU/kg/week subcutaneously 3 days/week/ 6 weeks. We used univariate and multivariate logistic regressions with PASW Statistics 18 for Windows. RESULTS: Data were obtained from 110 infants, with a mean birth weight of 1154grs and mean gestational age of 29.3 weeks. Risk factors (OR; 95% CI) for being transfused were: male sex (4.41; 1.24-15.66), GA (1.64; 1.14-2.36, 1 week), Hb level on admission (1.45; 1.04-2.04; 1g/dl), late onset sepsis (7.75; 2.21-21.11), late onset treatment with rh-EPO (6.27; 1.22-32.35). All surgically treated infants with patent ductus arteriosus ligation or necrotizing enterocolitis needed transfusion. There is no relationship between rh EPO administration and retinopathy of prematurity (ROP), but there was a relationship with transfusion. CONCLUSIONS: Premature infants with the lower gestational age, being male, a lower Hb level on admission and late onset sepsis are those with the greatest risk for blood transfusion. PMID- 21036114 TI - Serotonin transmembrane transporter is down-regulated in late-stage canine degenerative mitral valve disease. AB - OBJECTIVE: To compare expression of the serotonin transmembrane transporter (SERT) in normal, early-stage degenerative, and late-stage degenerative canine mitral valve disease. ANIMALS: 24 post-mortem canine mitral valves. METHODS: SERT expression was determined in canine normal (n = 8), early-stage degenerative (n = 8), and late-stage degenerative (n = 8) mitral valves by immunohistochemistry (IHC) and immunoblot (IB) analyses. RESULTS: SERT was expressed in valve interstitial cells of all layers of normal and early-stage degenerative mitral valves based on IHC. SERT was markedly down-regulated in valve interstitial cells, but not valve endothelial cells, of late-stage degenerative mitral valves. SERT expression was significantly decreased in late-stage compared to normal and early-stage degenerative mitral valves based on IB analysis (P < 0.05). CONCLUSIONS: Down-regulation of SERT expression occurs in valve interstitial cells of late-stage, but not early-stage, canine degenerative mitral valves. Down regulation of SERT could enhance the recently speculated role of serotonin in canine DMVD by decreasing serotonin metabolism and increasing interaction with its receptor. Down-regulation of SERT likely does not play an initiating role in canine DMVD since it does not occur in early-stage disease. PMID- 21036115 TI - "Zone of avoidance": RR interval distribution in tachograms, histograms, and Poincare plots of a Boxer dog. AB - The RR intervals of sinus and ventricular beats were determined by analysis of a 24-h ambulatory electrocardiogram in a Boxer before and after treatment with sotalol. These RR intervals were plotted using tachograms, histograms, and Poincare plots. The tachogram demonstrated a 'band' wherein a range of RR intervals was infrequent, the histogram did not take the form of a single Gaussian distribution of RR intervals, and the Poincare plot showed nonhomogeneous beat-to-beat variability. This type of patterning was described as a "zone of avoidance" potentially caused by the clustering of beats within specific ranges. Treatment with sotalol enhanced the "zone of avoidance". Further investigation is needed to understand the mechanism for this observation as well as any clinical implications. PMID- 21036116 TI - ACL injury and reconstruction: Clinical related in vivo biomechanics. AB - Several researchers including our group have shown that knee joint biomechanics are impaired after anterior cruciate ligament (ACL) injury, in terms of kinematics and neuromuscular control. Current ACL reconstruction techniques do not seem to fully restore these adaptations. Our research has demonstrated that after ACL reconstruction, excessive tibial rotation is still present in high demanding activities that involve both anterior and rotational loading of the knee. These findings seem to persist regardless of the autograft selection for the ACL reconstruction. Our results also suggest an impairment of neuromuscular control after ACL reconstruction, although muscle strength may have been reinstated. These abnormal biomechanical patterns may lead to loading of cartilage areas, which are not commonly loaded in the healthy knee and longitudinally can lead to osteoarthritis. Muscle imbalance can also influence patients' optimal sports performance exposing them to increased possibility of knee re-injury. In this review, our recommendations point towards further experimental work with in vivo and in vitro studies, in order to assist in the development of new surgical procedures that could possibly replicate more closely the natural ACL anatomy and prevent future knee pathology. PMID- 21036117 TI - Interest of complementary inferior glenohumeral ligament fixation in capsulo labral repair for shoulder instability: A biomechanical study. AB - Arthroscopic repair of Bankart lesions is part of the arsenal available to the shoulder surgeon to manage chronic anterior instability of the shoulder. Despite improvements in technique, rates of recurrence remain high. Some factors relate to the patients and their lesions, others to technique.The hypothesis that insufficient repair may be the cause of failure in Bankart arthroscopy was investigated in an anatomic and biomechanical study. Bankart lesions were made on 12 cadaver shoulders and repaired using two suture techniques. The aim was to investigate whether there was any biomechanical interest in reinforcing the labrum and capsule suture by a complementary inferior gleno-humeral ligament (IGHL) suture to double the labral repair. No significant difference in overall resistance was found between the two techniques. Failure generally started from the superior suture, and the present findings suggest that special attention should be paid to superior reinsertion. In the present model, complementary IGHL fixation did not alter the biomechanics of repair. Failure of repair can be traced to the superior suture. PMID- 21036118 TI - Early post-stroke physical conditioning in hemiplegic patients: A preliminary study. AB - OBJECTIVE: To establish the value of an early post-stroke evaluation of cardiorespiratory fitness in hemiparetic patients using a one-leg cycling exercise test and to analyze the impact of an adapted physical activity programme 12 weeks after the stroke. PROTOCOL: Eighteen hemiparetic stroke patients participated in the study. The subjects were randomly assigned to one of two groups: the control group (CG) underwent 4 weeks of conventional rehabilitation, whereas the training group (TG) performed additional physical exercises. The initial evaluation (T1) was carried out after 1 week of exercise and the final evaluation (T2) was performed after 28 days. Both evaluations consisted of maximal graded tests performed with the valid leg, followed by completion of a questionnaire on personal autonomy in activities of daily living (ADL). RESULTS: In the CG group, we recorded a 4 to 8% increase in peak oxygen uptake (VO2 peak). There was no significant increase in peak power output (Wpeak). However, the TG displayed significantly (P<0.05) greater peak values than those recorded on study entry (Wpeak: +30%, VO2 peak: +20%). The TG showed a statistically significant improvement in the Barthel and Katz ADL scale scores, whereas the pre- and post rehabilitation values did not differ significantly in the CG. However, there was no correlation between the Barthel/Katz scale scores and Wpeak. CONCLUSION: Evaluation of cardiorespiratory fitness by using the valid leg seems to be feasible in hemiplegic patients 1 month post-stroke. Early post-stroke physical training appears to be needed to limit the negative effects of functional hypoactivity. PMID- 21036119 TI - Geographic patterns of cancer in the population-based registry of Egypt: Possible links to environmental exposures. AB - BACKGROUND: We investigated the variation in cancer incidence in Gharbiah, Egypt to explore geographic differences in relation to demographic and environmental exposures. METHODS: Using data from the only population-based cancer registry of Gharbiah, we studied the 10 most common cancers in men and women over 4 years (1999-2002). Census data provided denominators and urban-rural definitions. Crude and adjusted incidence rates (IRs), incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were estimated using Poisson regression. RESULTS: Incidence of all common cancers was higher among men than women and urban incidence was higher than rural incidence for all cancer sites. Among men and women urban-rural incidence difference was highest for prostate cancer (IRR=4.85, 95% CI=3.76, 6.26) and uterus (IRR=6.05, 95% CI=4.17, 8.78), respectively. Among men and women, El-Santa district had the highest urban-rural difference within districts for laryngeal cancer (IRR=29.45, 95% CI=10.63, 81.61) and uterine cancer (IRR=15.98, 95% CI=2.69, 95.10), respectively. El-Santa also showed the highest urban incidence among all eight districts for most cancer sites. CONCLUSIONS: Geographic differences of cancers in Gharbiah need in-depth investigation with respect to specific environmental factors that explain the geographic cancer in this region. PMID- 21036120 TI - A review of 89 revision stapes surgeries for otosclerosis. AB - OBJECTIVES: The aim of this study was to identify the causes and the audiometric results of revision surgery following stapedotomies and stapedectomies. PATIENTS AND METHODS: We retrospectively reviewed a series of 89 revisions after surgery for otosclerosis between 1993 and 2008. Intraoperative findings, causes of failure, and pre- and postoperative audiometric results were noted retrospectively. RESULTS: The leading causes of failure found intraoperatively included dislocated prosthesis and necrosis of the long process of the incus. The average postoperative air-bone gap was 13 dB. Closure of the air-bone gap to within 10 dB was achieved in 52% of patients. CONCLUSION: Stapes revisions had less satisfactory results compared with primary procedures in this series. However, certain precautions during initial surgery should decrease the number of stapes surgery revisions. PMID- 21036121 TI - Malignant lacrimal sac tumors. AB - OBJECTIVES: Lacrimal sac tumors are usually primary and of epithelial origin. Overall, 55% of lacrimal sac tumors are malignant. Mortality rates for malignant tumors depend on tumor stage and type, with a mean rate of 38%. The main objective of this study was to review our experience with these malignancies and to compare this with the published literature. PATIENTS AND METHODS: A 15-year retrospective review of all malignant lacrimal sac tumor patients was completed in our department. Seven patients were found to have malignant sac tumors. The mean age was 53 years (range, 32-74 years) with six women and one man. The patients' clinical records were reviewed for data regarding patient symptoms, preoperative investigations, pathology reports, treatment results, and outcome. These data were compared with the available literature. RESULTS: All patients presented with epiphora and a palpable lump of the internal canthus. In two cases, a history of recurrent dacryocystitis was noted. The histological types were as follows: squamous cell carcinoma (n=5), one case of adenoid cystic carcinoma, and one case of malignant lymphoma. Surgery was performed in six cases with additional radiotherapy in four. One patient was treated exclusively with external radiotherapy. The mean follow-up was 68 months (range, 6-204 months). Two patients developed recurrences: three were disease-free at the time of the study. CONCLUSIONS: Malignant epithelial lacrimal sac tumors are rare cancers with significant recurrence rates. Correct diagnosis and appropriate therapy require a multidisciplinary management approach. Treatment of these malignant epithelial tumors is first and foremost complete surgical removal with wide excision. PMID- 21036122 TI - Enhanced airway smooth muscle cell thromboxane receptor signaling via activation of JNK MAPK and extracellular calcium influx. AB - Thromboxane is a key inflammatory mediator and potent airway constrictor. It acts on thromboxane A(2) (TP) receptors and contributes to airway inflammation and airway hyperresponsiveness that is the characteristic feature of asthma. The present study was designed to study TP receptor signaling in airway smooth muscle cells by using an organ culture model and a set of selective pharmacological inhibitors for mitogen-activated protein kinase (MAPK) and calcium signal pathways. Western-blot, immunohistochemistry, myograph and a selective TP receptor agonist U46619 were used for examining TP receptor signal proteins and function. Organ culture of rat bronchial segments for up to 48 h induces a time dependently increased airway contractile response to U46619. This indicates that organ culture increases TP receptor signaling in the airway smooth muscle cells. The enhanced bronchial contraction was attenuated by the inhibition of c-Jun N terminal kinase (JNK) MAPK activity, chelation of extracellular calcium and calcium channel blocker nifedipine, suggesting that JNK MAPK activity and elevated intracellular calcium level are required for the TP receptor signaling. In conclusion, airway smooth muscle cell TP receptor signaling occurs via JNK MAPK activity and the elevation of extracellular calcium influx, which may provide knowledge for understanding the signaling pathway responsible for the modulation of TP receptor mediated airway hyperresponsiveness to thromboxane. PMID- 21036123 TI - Caffeine/nutrition interaction in the rat brain: Influence on latent inhibition and cortical spreading depression. AB - Caffeine, like malnutrition, can produce behavioral and electrophysiological alterations. However, the interaction of both factors remains unclear. Here this interaction has been studied in male Wistar rats previously malnourished during the lactation period by feeding their dams the "regional basic diet" of Northeast Brazil, containing about 8% protein, predominantly from vegetable sources (RBD(8)). At 70-75days of life, a subset of the pups was treated intraperitoneally with 30mg/kg caffeine for 4days while being tested according to the behavioral model of latent inhibition. Another group was subjected to an electrophysiological recording of the phenomenon known as cortical spreading depression, and the effects of caffeine injected during the recording session were evaluated. Caffeine did not affect cortical spreading depression, but antagonized latent inhibition in both the RBD(8)-malnourished rats and in the well-nourished control group fed a chow diet with 22% protein. This effect of caffeine was not seen in malnourished rats fed a protein-supplemented RBD (protein increased to 22% by increasing the proportion of foodstuffs from vegetable origin; RBD(22) group), suggesting that the amino acid imbalance of this diet may modulate the caffeine effects on latent inhibition. The results indicate a differential effect of caffeine in the latent inhibition behavioral model, as compared to the cortical spreading depression phenomenon, and this effect is influenced by the early nutritional status of the animal. We suggest that caffeine may modulate dopaminergic subcortical receptors participating in attention processes, but does not interact at the cortical level, in a way that would affect cortical spreading depression. PMID- 21036124 TI - Tourniquet-induced acute ischemia-reperfusion injury in mouse skeletal muscles: Involvement of superoxide. AB - Although arterial limb tourniquet is one of the first-line treatments to prevent exsanguinating hemorrhage in both civilian pre-hospital and battlefield casualty care, prolonged application of a limb tourniquet can lead to serious ischemia reperfusion injury. However, the underlying pathomechanisms of tourniquet-induced ischemia-reperfusion injury are still poorly understood. Using a murine model of acute limb ischemia-reperfusion, we investigated if acute limb ischemia reperfusion injury is mediated by superoxide overproduction and mitochondrial dysfunction. Hind limbs of C57/BL6 mice were subjected to 3h ischemia and 4h reperfusion via placement and release of a rubber tourniquet at the greater trochanter. Approximately 40% of the gastrocnemius muscle suffered infarction in this model. Activities of mitochondrial electron transport chain complexes including complex I, II, III, and IV in the gastrocnemius muscle were decreased in the ischemia-reperfusion group compared to sham. Superoxide production was increased while activity of manganese superoxide dismutase (MnSOD, the mitochondria-targeted SOD isoform) was decreased in the ischemia-reperfusion group compared to the sham group. Pretreatment with tempol (a SOD mimetic, 50mg/kg) or co-enzyme Q(10) (50mg/kg) not only decreased the superoxide production, but also reduced the infarct size and normalized mitochondrial dysfunction in the gastrocnemius muscle. Our results suggest that tourniquet induced skeletal muscle ischemia-reperfusion injuries including infarct size and mitochondrial dysfunction may be mediated via superoxide overproduction and reduced antioxidant activity. In the future, this murine ischemia-reperfusion model can be adapted to mechanistically evaluate anti-ischemic molecules in tourniquet-induced skeletal muscle injury. PMID- 21036125 TI - Na(+)-H(+) exchange blockade, using amiloride, decreases the inflammatory response following hemorrhagic shock and resuscitation in rats. AB - Na(+)-H(+) exchanger activation on resuscitation following hemorrhagic shock has been shown to result in myocardial injury and dysfunction. Amiloride, an inhibitor of the Na(+)-H(+) exchanger has been shown to protect the myocardium against reperfusion injury in the ischemic hearts. However, the mechanism of protection remains unclear. Na(+)-H(+) exchanger blockers have been implicated in the regulation of inflammatory responses and chemokine production. The present study investigated the therapeutic anti-inflammatory value of amiloride on myocardial contractile function in post-resuscitation following hemorrhagic shock in rats. Male Sprague-Dawley rats were assigned into 3 groups: 1) hemorrhage, 2) hemorrhage treated with amiloride, and 3) sham hemorrhage (n=6 per group). Rats were hemorrhaged over 60min to reach a mean arterial blood pressure of 40mmHg. After 60min of hemorrhagic shock, rats were treated or not by injection of 1ml of 100MUM amiloride (0.027mg/ml) intra-arterially. Resuscitation was made in vivo by reinfusion of the shed blood to restore norm tension for 30min. Left ventricular contractile function was measured in the isolated hearts following hemorrhage and in vivo resuscitation using the Langendorff apparatus. Arterial blood samples were collected from all groups at the end of the experimental period (90min) for cytokine measurements (TNF-alpha). Amiloride decreased the inflammatory response to hemorrhagic shock and resuscitation by lowering the levels of TNF. These results indicate that amiloride protects the myocardium by down regulating the inflammatory response to hemorrhagic shock and resuscitation. PMID- 21036126 TI - Ibudilast, a mixed PDE3/4 inhibitor, causes a selective and nitric oxide/cGMP independent relaxation of the intracranial vertebrobasilar artery. AB - Ibudilast, a mixed phosphodiesterase (PDE) 3/4 inhibitor, is a cerebral vasodilator widely used in Japan for treating post-stroke dizziness. However, little studies have been conducted on the vasorelaxant effects of PDE inhibitors in the vertebrobasilar artery associated with dizziness onset. The in vitro vasorelaxant properties of ibudilast were, therefore, investigated by comparing with known selective PDE inhibitors, using vertebrobasilar arteries. Vasorelaxant activities of PDE3, PDE4, PDE5 inhibitors, and ibudilast were assessed in 5 hydroxytryptamine precontracted ring preparations from rabbit intracranial and extracranial vertebrobasilar arteries. Ibudilast more selectively relaxed the intracranial than extracranial artery. Similarly, selective PDE3 and PDE4 inhibitors showed higher selectivity for intracranial arteries. Furthermore, like selective PDE4 inhibitor, the vasorelaxation by ibudilast accompanied by increase in cAMP levels was inhibited by the adenylyl cyclase inhibitor SQ22536 in intracranial arteries. Next, it was examined whether nitric oxide (NO)/cGMP signaling is involved in this vasorelaxation in intracranial arteries. The suppression of NO/cGMP signaling by an NO synthase inhibitor or a guanylyl cyclase inhibitor potentiated the vasorelaxion by a PDE3 inhibitor and reduced that by a PDE4 inhibitor, while either suppression of the signaling had little influence on that by ibudilast. These results suggest that ibudilast has the high vasoselectivity for intracranial artery based on a mixed PDE3 and PDE4 inhibition, and effectively relaxes intracranial arteries independently of NO/cGMP signaling because of its vasorelaxation compensated by either PDE3- or PDE4-inhibition depending on the state of NO/cGMP signaling change. PMID- 21036127 TI - Peritoneal thickening of unknown origin. PMID- 21036128 TI - Germline epigenetic silencing of the tumor suppressor gene PTPRJ in early-onset familial colorectal cancer. PMID- 21036129 TI - WHO Working Group on technical specifications for manufacture and evaluation of dengue vaccines, Geneva, Switzerland, 11-12 May 2009. AB - In May 2009, a group of international experts on dengue, vaccine quality and clinical evaluation met together (i) to review disease, vaccine pipeline, quality issues in manufacturing, issues of environmental risk assessment, nonclinical and clinical evaluation of live recombinant dengue vaccines and (ii) to initiate revising WHO guidelines for the production and quality control of candidate tetravalent dengue vaccines (live). This report summarizes an exchange of views on scientific and technical issues related to the quality, safety and efficacy of candidate dengue vaccines. Recognizing live dengue vaccines are the major vaccines in the clinical pipeline, the Working Group agreed (i) to focus on live dengue vaccines in the revision of the WHO guidelines and (ii) to add new guidelines on nonclinical and clinical evaluation, and environmental risk assessment for live dengue vaccines in the revision. PMID- 21036131 TI - A novel antagonist of TLR9 blocking all classes of immunostimulatory CpG-ODNs. AB - The recognition of microbial CpG-DNA by toll-like receptor 9 (TLR9) might promote excessive inflammatory response or inflammatory disorder. To prevent possible clinical pathological injury following the TLR9 activation, here we have investigated a series of CpG-DNA sequences from conventional microbes using a bioinformatics tool of pattern search, and successfully identified CpG-ODN c41 from Pseudomonas aeruginosa genome, which contains a novel motif, '3 * N-CGCG'. Using ELISA and MTT assays, we found that CpG-ODN c41 was non-stimulatory and non cytotoxic and was able to inhibit the immunostimulatory activity caused by all classes of optimal stimulatory CpG-DNAs in murine 264.7 cells and human monocytes. Laser confocal microscopy demonstrated that CpG-ODN c41 competitively blocked the optimal stimulatory CpG-DNAs from binding to TLR9 in a dose-dependent fashion, thereby preventing TLR9 from triggering the inflammatory response. Moreover, CpG-ODN c41-mediated protection could take up a lethal challenge by stimulatory CpG-ODN in vivo. This study suggests that CpG-ODN c41 is a strong TLR9 antagonist that could be used as a therapeutic agent for CpG-ODN-mediated over-inflammatory responses, may also be used to treat autoimmune diseases. PMID- 21036132 TI - Factors associated with protective antibody levels to vaccine preventable diseases in internationally adopted children. AB - To determine which factors are predictive of protective antibody against vaccine preventable diseases in internationally adopted children, we evaluated 562 children with serologic testing for at least one vaccine antigen before receiving a US vaccination. Vaccination status was defined as the number-of-doses recorded and as the presence of an up-to-date and valid record according to the American Academy of Pediatrics and the Advisory Committee on Immunization Practices guidelines. The number-of-doses recorded was the best predictor of protective antibody. These findings suggest that other options for immunization verification guidelines for internationally adopted children should be considered by policy makers. PMID- 21036130 TI - Impact of ST-246(r) on ACAM2000TM smallpox vaccine reactogenicity, immunogenicity, and protective efficacy in immunodeficient mice. AB - Although a highly effective vaccine against smallpox, vaccinia virus (VV) is not without adverse events, some of which can be life-threatening, particularly in immunocompromised individuals. We have recently demonstrated that the immunogenicity and protective efficacy of Dryvax((r)) in immunocompetent mice is preserved even when co-administered with ST-246, an orally bioavailable small molecule inhibitor of orthopoxvirus egress and dissemination. In addition, ST-246 markedly reduced the reactogenicity of the smallpox vaccine ACAM2000 and the highly neurovirulent VV strain Western Reserve (VV-WR). Here, we evaluated the impact of ST-246 co-administration on ACAM2000 reactogenicity, immunogenicity, and protective efficacy in seven murine models of varying degrees of humoral and cellular immunodeficiency: BALB/c and B-cell deficient (JH-KO) mice depleted of CD4(+) or CD8(+) or both subsets of T cells. We observed that ST-246 reduced vaccine lesion severity and time to complete resolution in all of the immunodeficient models examined, except in those lacking both CD4(+) and CD8(+) T cells. Although VV-specific humoral responses were moderately reduced by ST-246 treatment, cellular responses were generally comparable or slightly enhanced at both 1 and 6 months post-vaccination. Most importantly, in those models in which vaccination given alone conferred protection against lethal VV challenge, similar levels of protection were observed at both time points when vaccination was given with ST-246. These data suggest that, with the exception of individuals with irreversible, combined CD4(+) and CD8(+) T-cell deficiency, ST-246 co administered at the time of vaccination may help reduce vaccine reactogenicity- even in those lacking humoral immunity--without impeding the induction of protective immunity. PMID- 21036133 TI - PCPP (poly[di(carboxylatophenoxy)-phosphazene]) microparticles co-encapsulating ovalbumin and CpG oligo-deoxynucleotides are potent enhancers of antigen specific Th1 immune responses in mice. AB - We generated poly[di(carboxylatophenoxy)-phosphazene] (PCPP) microparticles encapsulating ovalbumin (OVA) and CpG of 0.5-2.5 MUm in diameter with an encapsulation efficiency of approximately 63% and 95% respectively. In mice the microparticles generated high antigen-specific IgG, IgG1 and IgG2a titers with higher IgG2a/IgG1 ratios. Whole body in vivo imaging of mice subcutaneously injected with MPs showed several fold increase of OVA and CpG in draining inguinal lymph nodes compared to soluble formulations. We conclude that PCPP MPs are more effective in enhancing immune responses compared to soluble formulations, due to co-delivery of OVA and CpG resulting in a Th1 type of immune response. PMID- 21036134 TI - Application of the immunological disease continuum to study autoimmune and other inflammatory events after vaccination. AB - In vaccine safety monitoring, the evaluation of possible autoimmune events is challenging. Developing grouping systems based on pathophysiology, instead of organ systems, may enhance our ability to identify or verify associations between vaccines and adverse immunologically mediated events in clinical trials and post licensure surveillance. Emerging data suggest that self-directed tissue inflammation occurs along a continuum from innate immune-driven diseases to adaptive immune-driven diseases. Herein, we develop this proposed classification for the vaccination setting in which inflammatory diseases are placed along a continuum according to the two major arms of the immune system, the innate immune arm (mediated by cells including neutrophils, macrophages and complement) and the adaptive immune arm (cell-mediated and humoral response). We incorporate hypersensitivity reactions and molecular mimicry vaccine-related reactions into this mechanistic scheme. We show how this could have important implications to assess mechanisms of potential immune-mediated adverse events following vaccination. PMID- 21036135 TI - Selection of reference genes in Hedysarum coronarium under various stresses and stages of development. AB - The cultivation of Hedysarum coronarium has generated interest recently for its high yield as a fodder crop, its high protein content, and the presence of condensed tannins in its leaf and stem tissues. Gene expression studies can lead to a better understanding of the biological processes of live organisms. Specifically, reverse transcription followed by quantitative polymerase chain reaction (PCR) represents the most powerful technology for comparing the expression profiles of target genes. The use of reference genes as internal controls to normalize messenger RNA (mRNA) levels is a requirement of quantitative PCR (qPCR). Few studies on reference genes have been performed in plants, and no studies have been performed in H. coronarium. Therefore, the aim of this study was to identify and evaluate reference genes to use in qPCR in H. coronarium. Sulla tissues under two conditions of abiotic stress and at various stages of development were studied to determine adequate reference genes. To optimize the identity and number of reference genes, geNorm and BestKeeper software programs were employed. Based on the results of both analyses, TUA1, TUA2, and UBQ were found to be the most suitable reference genes, and the combination of these three genes was suggested for the accurate normalization of gene expression in sulla tissues. PMID- 21036136 TI - A simplified method for rapid quantification of intracellular nucleoside triphosphates by one-dimensional thin-layer chromatography. AB - Quantification of nucleotides is an important part of metabolomics but has been hampered by the lack of fast, sensitive, and reliable methods. We present a less time-consuming, more sensitive, and more precise method for the quantitative determination of nucleoside triphosphates (NTPs), 5-ribosyl-1-pyrophosphate (PRPP), and inorganic pyrophosphate (PP(i)) in cell extracts. The method uses one dimensional thin-layer chromatography (TLC) and radiolabeled biological samples. Nucleotides are resolved at the level of ionic charge in an optimized acidic ammonium formate and chloride solvent, permitting quantification of NTPs. The method is significantly simpler and faster than both current two-dimensional methods and high-performance liquid chromatography (HPLC)-based procedures, allowing a higher throughput while common sources of inaccuracies and technical problems are avoided. For determination of PP(i), treatment with inorganic pyrophosphatase (PPase) of the radiolabeled phosphate is employed for removal of contaminating pyrophosphate. Biological examples performed in triplicates showed standard deviations of approximately 10% of the mean for the determined concentrations of NTPs. PMID- 21036137 TI - Quantification of interactions between drug leads and serum proteins by use of "binding efficiency". AB - To develop efficient and reliable methods for prediction of serum protein binding of drug leads, the kinetic characteristics for the interactions between selected compounds and human serum albumin and alpha1-acid glycoprotein have been explored using a surface plasmon resonance biosensor. Conventional methods for quantification of interactions (i.e., using rate constants or affinities determined on the basis of a reasonable mechanistic model) were applicable for only a few of the compounds. The affinity of a primary interaction and the contribution of lower affinity secondary interactions could be estimated for some compounds, but the affinity of many compounds could not be quantified by either of these methods. To have a quantification method that could be used for all compounds, independent of affinity and complexity of interaction mechanisms, the concept of "binding efficiency," analogous to "catalytic efficiency" used for enzymes, was developed. It allowed the quantification of the binding of compounds interacting with weak affinity and for which saturation is not reached within a concentration range where the compound is soluble or when the influence of interactions with secondary sites makes interpretations difficult. In addition, compounds with large fractional binding can be identified by this strategy and simply quantified relative to reference compounds. This approach will enable ranking and identification of structure-activity relationships of compounds with respect to their serum protein binding profile. PMID- 21036138 TI - Structural alterations of the FAS gene in cutaneous T-cell lymphoma (CTCL). AB - FAS (TNF receptor superfamily member 6, also known as CD95) plays a major role in T-cell apoptosis and is often dysregulated in CTCL. We searched for structural alterations of the FAS gene with the potential to affect its function. Although several heterozygous FAS promoter single nucleotide polymorphisms (SNPs) were detected, the only homozygous one was the -671 GG SNP present in 24/80 CTCL cases (30%). This SNP maps to an interferon response element activated by STAT-1. EMSA and supershift EMSA showed decreased CTCL nuclear protein/STAT-1 binding to oligonucleotides bearing this SNP. Luciferase reporters showed significantly less interferon-alfa responsive expression by FAS promoter constructs containing this SNP in multiple CTCL lines. Finally, FAS was upregulated by interferon-alfa in wildtype CTCL cells but not those bearing the -671 GG SNP. These findings indicate that many CTCL patients harbor the homozygous FAS promoter -671 GG SNP capable of blunting its response to interferon. This may have implications for CTCL pathogenesis, racial incidence and the response of patients to interferon alfa therapy. In contrast, functionally significant mutations in FAS coding sequences were detected uncommonly. Among CTCL lines with the potential to serve as models of FAS regulation, FAS-high MyLa had both FAS alleles, FAS-low HH was FAS-hemizygous and FAS-negative SeAx was FAS-null. PMID- 21036139 TI - Effects of formate binding on the quinone-iron electron acceptor complex of photosystem II. AB - EPR was used to study the influence of formate on the electron acceptor side of photosystem II (PSII) from Thermosynechococcus elongatus. Two new EPR signals were found and characterized. The first is assigned to the semiquinone form of Q(B) interacting magnetically with a high spin, non-heme-iron (Fe2(+), S=2) when the native bicarbonate/carbonate ligand is replaced by formate. This assignment is based on several experimental observations, the most important of which were: (i) its presence in the dark in a significant fraction of centers, and (ii) the period-of-two variations in the concentration expected for Q(B)(*-) when PSII underwent a series of single-electron turnovers. This signal is similar but not identical to the well-know formate-modified EPR signal observed for the Q(A)(* )Fe2(+) complex (W.F.J. Vermaas and A.W. Rutherford, FEBS Lett. 175 (1984) 243 248). The formate-modified signals from Q(A)(*-)Fe2(+) and Q(B)(*-)Fe2(+) are also similar to native semiquinone-iron signals (Q(A)(*-)Fe2(+)/Q(B)(*-)Fe2(+)) seen in purple bacterial reaction centers where a glutamate provides the carboxylate ligand to the iron. The second new signal was formed when Q(A)(*-) was generated in formate-inhibited PSII when the secondary acceptor was reduced by two electrons. While the signal is reminiscent of the formate-modified semiquinone-iron signals, it is broader and its main turning point has a major sub-peak at higher field. This new signal is attributed to the Q(A)(*-)Fe2(+) with formate bound but which is perturbed when Q(B) is fully reduced, most likely as Q(B)H2 (or possibly Q(B)H(*-) or Q(B)(2*-)). Flash experiments on formate inhibited PSII monitoring these new EPR signals indicate that the outcome of charge separation on the first two flashes is not greatly modified by formate. However on the third flash and subsequent flashes, the modified Q(A)(* )Fe2(+)Q(B)H2 signal is trapped in the EPR experiment and there is a marked decrease in the quantum yield of formation of stable charge pairs. The main effect of formate then appears to be on Q(B)H2 exchange and this agrees with earlier studies using different methods. PMID- 21036140 TI - Far-red light-regulated efficient energy transfer from phycobilisomes to photosystem I in the red microalga Galdieria sulphuraria and photosystems-related heterogeneity of phycobilisome population. AB - Phycobilisomes (PBS) are the major photosynthetic antenna complexes in cyanobacteria and red algae. In the red microalga Galdieria sulphuraria, action spectra measured separately for photosynthetic activities of photosystem I (PSI) and photosystem II (PSII) demonstrate that PBS fraction attributed to PSI is more sensitive to stress conditions and upon nitrogen starvation disappears from the cell earlier than the fraction of PBS coupled to PSII. Preillumination of the cells by actinic far-red light primarily absorbed by PSI caused an increase in the amplitude of the PBS low-temperature fluorescence emission that was accompanied by the decrease in PBS region of the PSI 77 K fluorescence excitation spectrum. Under the same conditions, fluorescence excitation spectrum of PSII remained unchanged. The amplitude of P700 photooxidation in PBS-absorbed light at physiological temperature was found to match the fluorescence changes observed at 77 K. The far-red light adaptations were reversible within 2-5min. It is suggested that the short-term fluorescence alterations observed in far-red light are triggered by the redox state of P700 and correspond to the temporal detachment of the PBS antenna from the core complexes of PSI. Furthermore, the absence of any change in the 77 K fluorescence excitation cross-section of PSII suggests that light energy transfer from PBS to PSI in G. sulphuraria is direct and does not occur through PSII. Finally, a novel photoprotective role of PBS in red algae is discussed. PMID- 21036141 TI - The influence of additives on the nanoscopic dynamics of the phospholipid dimyristoylphosphatidylcholine. AB - The influence of additives on the molecular dynamics of the phospholipid dimyristoylphosphatidylcholine (DMPC) in its fully hydrated liquid crystalline phase was studied. Quasielastic neutron scattering (QENS) was used to detect motions with dimensions of some Angstroms on two different time scales, namely 60ps and 900ps. The effects of myristic acid, farnesol, cholesterol, and sodium glycocholate could consistently be explained on the basis of collective, flow like motions of the phospholipid molecules. The influence of the additives on these motions was explained by packing effects, corresponding to the reduction of free volume. Cholesterol was found to decrease the mobility of DMPC seen on the 900ps time scale with increasing cholesterol content. In contrast, all other studied additives have no significant effect on the mobility. PMID- 21036142 TI - Liposome-incorporated DHA increases neuronal survival by enhancing non amyloidogenic APP processing. AB - The fluidity of neuronal membranes plays a pivotal role in brain aging and neurodegeneration. In this study, we investigated the role of the omega-3 fatty acid docosahexaenoic acid (DHA) in modulation of membrane fluidity, APP processing, and protection from cytotoxic stress. To this end, we applied unilamellar transfer liposomes, which provided protection from oxidation and effective incorporation of DHA into cell membranes. Liposomes transferring docosanoic acid (DA), the completely saturated form of DHA, to the cell cultures served as controls. In HEK-APP cells, DHA significantly increased membrane fluidity and non-amyloidogenic processing of APP, leading to enhanced secretion of sAPPalpha. This enhanced secretion of sAPPalpha was associated with substantial protection against apoptosis induced by ER Ca(2+) store depletion. sAPPalpha-containing supernatants obtained from HEK-APP cells exerted similar protective effects as DHA in neuronal PC12 cells and HEK293 control cells. Correlating to further increased sAPPalpha levels, supernatants obtained from DHA treated HEK-APP cells enhanced protection, whereas supernatants obtained from DHA treated HEK293 control cells did not inhibit apoptosis, likely due to the low expression of endogenous APP and negligible sAPPalpha secretion in these cells. Further experiments with the small molecule inhibitors LY294002 and SP600125 indicated that sAPPalpha-induced cytoprotection relied on activation of the anti apoptotic PI3K/Akt pathway and inhibition of the stress-triggered JNK signaling pathway in PC12 cells. Our data suggest that liposomal DHA is able to restore or maintain physiological membrane properties, which are required for neuroprotective sAPPalpha secretion and autocrine modulation of neuronal survival. PMID- 21036143 TI - Is an orthorhombic lateral packing and a proper lamellar organization important for the skin barrier function? AB - The lipid organization in the stratum corneum (SC), plays an important role in the barrier function of the skin. SC lipids form two lamellar phases with a predominantly orthorhombic packing. In previous publications a lipid model was presented, referred to as the stratum corneum substitute (SCS), that closely mimics the SC lipid organization and barrier function. Therefore, the SCS serves as a unique tool to relate lipid organization with barrier function. In the present study we examined the effect of the orthorhombic to hexagonal phase transition on the barrier function of human SC and SCS. In addition, the SCS was modified by changing the free fatty acid composition, resulting in a hexagonal packing and perturbed lamellar organization. By measuring the permeability to benzoic acid as function of temperature, Arrhenius plots were constructed from which activation energies were calculated. The results suggest that the change from orthorhombic to hexagonal packing in human SC and SCS, does not have an effect on the permeability. However, the modified SCS revealed an increased permeability to benzoic acid, which we related to its perturbed lamellar organization. Thus, a proper lamellar organization is more crucial for a competent barrier function than the presence of an orthorhombic lateral packing. PMID- 21036144 TI - The relationship between GPR40 and lipotoxicity of the pancreatic beta-cells as well as the effect of pioglitazone. AB - Free fatty acids (FFAs) acutely stimulate insulin secretion from pancreatic beta cells, whereas impair beta-cell function following long term exposure. GPR40, a FFAs receptor, has been demonstrated to be activated by both medium and long chain FFAs and played an important role in insulin release. This study was performed to determine the contribution of GPR40 to short- and/or long-term effects of FFAs on glucose-stimulated insulin secretion (GSIS) and the expression of PDX-1 and GLUT2 in pancreatic beta-cells, as well as the intervenient effects of pioglitazone on lipotoxicity of beta-cells. betaTC6 cell line stably expressing GPR40shRNA were established and the intervention of FFAs and pioglitazone on GSIS and expression of PDX-1 and GLUT2 in betaTC6 cells was investigated. Results showed that 1-h exposure to FFAs significantly enhanced GSIS and increased expression of PDX-1 and GLUT2 in pSilencer-control transfected cells, but not in cells transfected with GPR40shRNA. While 48-h exposure to FFAs significantly impaired GSIS in pSilencer-control transfected cells as well as cells transfected with GPR40shRNA. Furthermore, pioglitazone enhanced insulin secretion in pSilencer-control transfected cells exposed to FFAs for 48h, but not in cells transfected with GPR40shRNA. These results indicate that GPR40 mediates the short-term effects of FFAs on GSIS, but does not mediate the chronic lipotoxicity on beta-cells. The reverse role of pioglitazone on lipotoxicity of beta-cells may be related to GPR40. PMID- 21036145 TI - Mitochondrial translocation of signal transducer and activator of transcription 5 (STAT5) in leukemic T cells and cytokine-stimulated cells. AB - Signal transducers and activators of transcription (STATs) were first identified as key signaling molecules in response to cytokines. Constitutive STAT activation also has been widely implicated in oncogenesis. We analyzed STAT5-associated proteins in a leukemic T cell line LSTRA, which exhibits constitutive tyrosine phosphorylation and activation of STAT5. A cellular protein was found to specifically interact with STAT5 in LSTRA cells by co-immunoprecipitation. Sequencing analysis and subsequent immunoblotting confirmed the identity of this STAT5-associated protein as the E2 component of mitochondrial pyruvate dehydrogenase complex (PDC-E2). Consistent with this interaction, both subcellular fractionation and immunofluorescence microscopy revealed mitochondrial localization of STAT5 in LSTRA cells. Mitochondrial localization of tyrosine-phosphorylated STAT5 also occurred in cytokine-stimulated cells. A time course experiment further demonstrated the transient kinetics of STAT5 mitochondrial translocation after cytokine stimulation. In contrast, cytokine induced STAT1 and STAT3 activation did not result in their translocation into mitochondria. Furthermore, we showed that mitochondrial STAT5 bound to the D-loop regulatory region of mitochondrial DNA in vitro. It suggests a potential role of STAT5 in regulating the mitochondrial genome. Proliferative metabolism toward aerobic glycolysis is well known in cancer cells as the Warburg effect and is also observed in cytokine-stimulated cells. Our novel findings of cytokine induced STAT5 translocation into mitochondria and its link to oncogenesis provide important insights into the underlying mechanisms of this characteristic metabolic shift. PMID- 21036146 TI - Development of experimental cerebral malaria is independent of IL-23 and IL-17. AB - Cerebral malaria (CM) is the most severe complication of Plasmodium infection. Although inappropriate immune responses to Plasmodium falciparum are reported as the major causes of CM, the precise mechanisms for development remain unclear. IL 23 and IL-17 have critical roles in the onset of autoimmunity and inflammatory diseases triggered by microbial infections. Thus, we investigated the influence of IL-23 and IL-17 on experimental CM (ECM) using Plasmodium berghei ANKA infection of C57BL/6 mice. Both IL-23 deficient mice and wild-type (WT) mice developed ECM. IL-17 deficient mice also developed ECM, while IL-17 producing cells other than CD4(+) T cells (Th17) were increased in WT mice that developed ECM. In conclusion, this study showed that IL-23 and IL-17 are not involved in ECM development. PMID- 21036147 TI - The role of O-linked GlcNAc modification on the glucose response of ChREBP. AB - The carbohydrate response element-binding protein (ChREBP) functions as a transcription factor in mediating the glucose-activated gene expression of multiple liver enzymes, which are responsible for converting excess carbohydrate to storage fat. ChREBP is translocated into the nucleus in response to high glucose levels, and then up-regulates transcriptional activity. Although this glucose activation of ChREBP is generally observed only in liver cells, overexpression of wild type max-like protein X (Mlx), but not an inactive mutant Mlx, resulted in the exhibition of the ChREBP functions also in a human kidney cell line. Because high glucose conditions induce the glycosylation of cellular proteins, the effect of O-linked GlcNAc modification on ChREBP functions was examined. Treatment with an O-GlcNAcase inhibitor (PUGNAc), which increases the O linked GlcNAc modification of cellular proteins, caused an increase in the glucose response of ChREBP. In contrast, treatment with a glutamine fructose amidotransferase inhibitor (DON), which decreases O-GlcNAcylation by inhibiting the hexosamine biosynthetic pathway, completely blocked the glucose response of ChREBP. These results suggest that the O-linked glycosylation of ChREBP itself or other proteins that regulate ChREBP is essential for the production of functional ChREBP. PMID- 21036148 TI - Static pressure accelerates ox-LDL-induced cholesterol accumulation via SREBP-1 mediated caveolin-1 downregulation in cultured vascular smooth muscle cells. AB - OBJECTIVE: To investigate the effect of static pressure on cholesterol accumulation in vascular smooth muscle cells (VSMCs) and its mechanism. METHODS: Rat-derived VSMC cell line A10 treated with 50mg/L ox-LDL and different static pressures (0, 60, 90, 120, 150, 180 mm Hg) in a custom-made pressure incubator for 48 h. Intracellular lipid droplets and lipid levels were assayed by oil red O staining and HPLC; The mRNA levels of caveolin-1 and ABCA1, the protein levels of caveolin-1 SREBP-1 and mature SREBP-1 were respectively detected by RT-PCR or western blot. ALLN, an inhibitor of SREBP metabolism, was used to elevate SREBP-1 protein level in VSMCs treated with static pressure. RESULTS: Static pressures significantly not only increase intracellular lipid droplets in VSMCs, but also elevate cellular lipid content in a pressure-dependent manner. Intracellular free cholesterol (FC), cholesterol ester (CE), total cholesterol (TC) were respectively increased from 60.5 +/- 2.8 mg/g, 31.8 +/- 0.7 mg/g, 92.3 +/- 2.1mg/g at atmosphere pressure (ATM, 0 mm Hg) to 150.8 +/- 9.4 mg/g, 235.9 +/- 3.0mg/g, 386.7 +/- 6.4 mg/g at 180 mm Hg. At the same time, static pressures decrease the mRNA and protein levels of caveolin-1, and induce the activation and nuclear translocation of SREBP-1. ALLN increases the protein level of mature SREBP-1 and decreases caveolin-1 expression, so that cellular lipid levels were upregulated. CONCLUSION: Static pressures stimulate ox-LDL-induced cholesterol accumulation in cultured VSMCs through decreasing caveolin-1 expression via inducing the maturation and nuclear translocation of SREBP-1. PMID- 21036149 TI - A novel adipokine GM2AP impairs insulin signaling. AB - In an attempt to discover novel adipokines, we performed proteomics analyses using culture medium from differentiated 3T3-L1 adipocytes, and first identified GM2AP. The levels of GM2AP mRNA and protein were augmented by adipogenesis in cultured adipocytes and expression in adipose tissue and serum of obese mice or human subjects was found to be significantly higher than in lean counterparts. Exposure of 3T3-L1 adipocytes to GM2AP protein accelerated dissociation of insulin receptor-beta (IRbeta) from caveolin-1, and interrupted insulin signal transduction. Abrogation of GM2AP function by specific antibodies augmented glucose uptake. Furthermore, treatment of rat pheochromocytoma PC12 NS1 cells with GM2AP impaired NGF signal transduction. Taken together, these results provide novel insights into the physiological functions of GM2AP in obesity. PMID- 21036150 TI - The role of active site residues in the oxidant specificity of the Orp1 thiol peroxidase. AB - In this study we investigated the role of active site residues in the peroxidase activity of Orp1 (GPx3) using three different peroxide substrates. Using a structural homology model of the reduced form of Orp1, we identified Asn126 and Phe127 as evolutionarily conserved residues that line the back of the Orp1 active site and which are likely to affect the peroxidase activity of Orp1. Additionally, we identified Phe38 as a surface residue that could influence substrate specificity as it is located adjacent to Cys36, in the same position occupied by similar hydrophobic amino acids in many Orp1 homologs. We individually mutated these residues to alanine and examined the effect of each mutation in vitro and in vivo. Chloro-4-nitrobenzo-2-oxa-1,3-diazole was used to identify Cys-SOH modification of Cys36 in response to H(2)O(2), tert-butyl hydroperoxide (tert-BHP), and cumene hydroperoxide (CHP) in Orp1(WT). Mutation of Asn126 and Phe127 eliminate Cys-SOH formation and peroxidase activity in response to H(2)O(2), tert-BHP and CHP. Furthermore, the pK(a) of Cys36 is elevated closer to that of free cysteine compared to Orp1(WT). Mutation of Phe38 does not affect the peroxidase activity of Orp1 upon exposure to H(2)O(2). The Phe38 mutation decreases Orp1 peroxidase activities in response to either tert-BHP or CHP. The in vivo sensitivity of the Phe38 mutant to both tert-BHP and CHP is increased, while the H(2)O(2) sensitivity is unchanged. The pK(a) of Cys36 in the Phe38 mutant is 5.0, which is the same as Orp1(WT). Taken together, these results suggest that Phe38 does not play a role in the reactivity of Cys36, but does modulate the affinity of Orp1 for alkyl hydroperoxides. PMID- 21036151 TI - Hemolysis of human erythrocytes induced by melamine-cyanurate complex. AB - Melamine is a widely-used chemical in industries. In recent years, melamine has been found to be involved in outbreaks of renal injury in infants and animals. Pathological studies indicated that the melamine-induced acute renal failure was related to the concurrence of melamine and other triazine analogs such as cyanuric acid. In the present study, human erythrocytes were used as an in vitro model to explore the cytotoxicity of melamine and its complex with cyanuric acid. The results demonstrated that mixing melamine and cyanuric acid resulted in the formation of insoluble particles and that the insoluble melamine-cyanurate complex induced membrane damages of human erythrocytes. The membrane damages included hemolysis, K(+) leakage, alterations in cell shape and membrane fragility, and inhibition of enzymatic activity. By contrast, either melamine or cyanuric acid alone had no effect on erythrocyte membranes. The results of this study may provide a fresh insight into the melamine toxicology. PMID- 21036152 TI - Regulation of the promoter region of the human adiponutrin/PNPLA3 gene by glucose and insulin. AB - The adiponutrin/PNPLA3 gene is highly expressed in adipose tissue and liver. Its expression is down-regulated by fasting and rapidly induced by refeeding a high carbohydrate diet. We aimed to determine whether the promoter region of adiponutrin is regulated by glucose and insulin. Endogenous adiponutrin mRNA was increased in mouse 3T3-L1 and human SGBS adipocytes and in human HepG2 cells cultured in 25 mM glucose compared to absence of glucose. A 3100 bp 5'-upstream region of the human adiponutrin gene was cloned into a luciferase reporter plasmid and used in transient transfection studies. Promoter activity was up regulated by 25 mM glucose, 4.7-fold in HepG2 cells and 2-fold in CHO cells. The effect was shown in CHO cells to be concentration dependent and to depend on glucose metabolism as a non-metabolisable analogue was without effect. In CHO cells constitutively expressing human insulin receptor (CHO-IR), there was a concentration dependent increase of promoter activity by insulin in the presence of glucose. Cotransfection with an expression plasmid for upstream stimulatory factor 2 (USF2), increased promoter activity 1.6-fold in CHO-IR cells. The combined effect of insulin and USF2 (2.3-fold) was greater than the individual effects. Cotransfection of carbohydrate-response element binding protein did not elicit any induction of promoter activity. These results point to potential mechanisms for the observed in vivo nutritional regulation of adiponutrin expression and its up-regulation in fatty liver and by obesity. PMID- 21036153 TI - Identification of a novel Vpr-binding compound that inhibits HIV-1 multiplication in macrophages by chemical array. AB - Although HIV-1 replication can be controlled by highly active anti-retroviral therapy (HAART) using protease and reverse transcriptase inhibitors, the development of multidrug-resistant viruses compromises the efficacy of HAART. Thus, it is necessary to develop new drugs with novel targets. To identify new anti-HIV-1 compounds, recombinant Vpr was purified from transfected COS-7 cells and used to screen compounds by chemical array to identify those that bound Vpr. From this screen, 108 compounds were selected as positive for Vpr binding. Among these, one structurally similar group of four compounds showed anti-HIV activity in macrophages. In particular, compound SIP-1 had high inhibition activity and reduced the levels of p24 by more than 98% in macrophages after 8 or 12 days of infection. SIP-1 had no cytotoxic effects and did not disrupt cell cycle progression or induce apoptosis of Molt-4 and HeLa cell lines as measured by MTT assay, flow-cytometry analysis, and a caspase-3 assay. In addition, SIP-1 specifically bound to Vpr as assessed by photo-cross-linked small-molecule affinity beads. These results suggest that Vpr is a good target for the development of compounds that could potentially inhibit HIV-1 replication. Collectively, our results strongly suggest that chemical array is a useful method for screening anti-viral compounds. PMID- 21036154 TI - Insulin metabolism in human adipocytes from subcutaneous and visceral depots. AB - Subjects with the metabolic syndrome (insulin resistance, glucose intolerance, dyslipidemia, hypertension, etc.) have a relative increase in abdominal fat tissue compared to normal individuals and obesity has also been shown to be associated with a decrease in insulin clearance. The majority of the clearance of insulin is due to the action of insulin-degrading enzyme (IDE) and IDE is present throughout all tissues. Since abdominal fat is increased in obesity we hypothesized that IDE may be altered in the different fat depots. Adipocytes were isolated from fat samples obtained from subjects during elective abdominal surgery. Fat samples were taken from subcutaneous (SQ) and visceral (VIS) sites. Insulin metabolism was compared in adipocytes isolated from SQ and VIS fat tissue. Adipocytes from the VIS site degraded more insulin that those from SQ fat tissue. Inhibitors of cathepsins B and D has no effect on the degradation of insulin, while bacitracin, an inhibitor of IDE, inhibited degradation by approx. 33% in both SQ and VIS adipocytes. These data show that insulin metabolism is relatively greater in VIS than in SQ fat tissue and potentially due to IDE. PMID- 21036156 TI - Designing a highly active soluble PQQ-glucose dehydrogenase for efficient glucose biosensors and biofuel cells. AB - We report for the first time a soluble PQQ-glucose dehydrogenase that is twice more active than the wild type for glucose oxidation and was obtained by combining site directed mutagenesis, modelling and steady-state kinetics. The observed enhancement is attributed to a better interaction between the cofactor and the enzyme leading to a better electron transfer. Electrochemical experiments also demonstrate the superiority of the new mutant for glucose oxidation and make it a promising enzyme for the development of high-performance glucose biosensors and biofuel cells. PMID- 21036155 TI - Molecular mechanisms of the inhibitory effect of lipopolysaccharide (LPS) on osteoblast differentiation. AB - Osteoblasts express Toll like receptor (TLR) 4 and produce osteoclast-activating cytokines in response to the stimulation by lipopolysaccharide (LPS). It has recently been reported that LPS exerts an inhibitory effect on osteoblast differentiation into osteocytes. However, the molecular mechanisms of this inhibitory effect remain ambiguous. The downstream signals of TLR4 are mediated by adaptor molecules including myeloid differentiation factor 88 (MyD88), leading to the activation of mitogen-activated protein kinases (MAPKs), such as extracellular signal-regulated kinases (ERKs), whose activation by LPS requires the upstream serine/threonine kinase, Cot/Tpl2. To determine the signal molecules responsible for the inhibitory effects of LPS on osteoblast differentiation, we examined the in vitro differentiation of the primary osteoblasts from myd88(-/-) and cot/tpl2(-/-) mice. The matrix mineralization by the wild-type and cot/tpl2( /-) osteoblasts was significantly inhibited by LPS, whereas that of myd88(-/-) was not affected. During differentiation, LPS suppressed the mRNA expression of runt related transcription factor 2 (Runx2), osterix (Sp7), and activating transcription factor 4 (ATF4) in the wild-type, but not in the myd88(-/-) osteoblasts. The inhibitory effect of LPS on the mRNA expression of these transcription factors was absent in the early phase but partially impaired in the late phase of differentiation in the cot/tpl2(-/-) osteoblasts. Thus, the inhibitory effect of LPS on osteoblast differentiation is Myd88-dependent, whereas the degree of its requirement for Cot/Tpl2 varies depending on the differentiation phase. PMID- 21036157 TI - Heme controls the regulation of protein tyrosine kinases Jak2 and Src. AB - Protein tyrosine kinases play key roles in many molecular and cellular processes in diverse living organisms. Their proper functioning is crucial for the normal growth, development, and health in humans, whereas their dysfunction can cause serious diseases, including various cancers. As such, intense studies have been performed to understand the molecular mechanisms by which the activities of protein tyrosine kinases are regulated in mammalian cells. Particularly, small molecules that can modulate the activity of tyrosine kinases are of great importance for discovering therapeutic drug candidates for numerous diseases. Notably, heme cannot only serve as a prosthetic group for hemoglobins and enzymes, but it also is a small signaling molecule that can control the activity of diverse signaling and regulatory proteins. Using a computational search, we found that a group of non-membrane spanning tyrosine kinases contains one or more CP motifs that can potentially bind to heme and mediate heme regulation. We then used experimental approaches to determine whether heme can affect the activity of any of these tyrosine kinases. We found that heme indeed affects the phosphorylation of key tyrosine residues in Jak2 and Src, and is therefore able to modulate Jak2 and Src activity. Further experiments showed that Jak2 and Src bind to heme and that the presence of heme alters the sensitivity of Jak2 and Src to trypsin digestion. These results suggest that heme actively interacts with Jak2 and Src and alters their conformation. PMID- 21036158 TI - Cortico-limbic-striatal contribution after response and reversal learning: a metabolic mapping study. AB - Learning of arbitrary stimulus-response associations is an adaptive behavior essential for species survival in an ever-changing environment. Particular subdivisions of the striatum have been shown to be critical for both motor response learning and reversal learning. However, recent evidence suggests that different cortical and subcortical brain regions may be involved in response learning, a kind of learning more complex than previously thought. In fact, many brain regions subserving response learning seem to be also related to reversal learning, traditionally ascribed to the prefrontal cortex. The present study examined the role of different subdivisions of the rat prefrontal cortex, striatum, amygdala and the ventral tegmental area on both response and reversal learning evaluated in the water T-maze. Increased neuronal metabolic activity, as measured by cytochrome oxidase (CO) histochemistry, was found in most brain regions after training rats in a response learning task as compared to yoked controls. Reversal learning was associated with a return to baseline CO activity levels except for the orbitofrontal cortex and the ventral tegmental area. Analysis of functional connectivity among brain regions showed significant correlations in CO activity between particular cortical and striatal subdivisions in the reversal learning group. These findings suggest that the interaction of specific frontal and subcortical regions is required for reversal but not for response learning. However, our findings support the involvement of a cortico limbic-striatal circuit in both types of learning. PMID- 21036159 TI - Closing the anion gap: contribution of D-lactate to diabetic ketoacidosis. AB - BACKGROUND: A high anion gap in diabetic ketoacidosis (DKA) suggests that some unmeasured anions must contribute to the generation of the anion gap. We investigated the contribution of D-lactate to the anion gap in DKA. METHODS: Diabetic patients with and without DKA and high anion gap were recruited. Plasma D-lactate was quantified by HPLC. Plasma methylglyoxal was assayed by liquid chromatography-tandem mass spectrometry. RESULTS: The plasma fasting glucose, beta-hydroxybutyrate, and blood HbA1c levels were highly elevated in DKA. Plasma anion gap was significantly increased in DKA (20.59+/-6.37) compared to either the diabetic (7.50+/-1.88) or the control group (6.53+/-1.75) (p<0.001, respectively). Moreover, plasma D-lactate levels were markedly increased in DKA (3.82+/-2.50 mmol/l) compared to the diabetic (0.47+/-0.55 mmol/l) or the control group (0.25+/-0.35 mmol/l) (p<0.001, respectively). Regression analysis demonstrated that D-lactate was associated with acidosis and anion gap (r=0.686, p<0.001). CONCLUSIONS: Plasma D-lactate levels are highly elevated and associated with metabolic acidosis and the high anion gap in DKA. Laboratory monitoring of d lactate will provide valuable information for assessment of patients with DKA. PMID- 21036160 TI - Lipid plasma concentrations of HDL subclasses determined by enzymatic staining on polyacrylamide electrophoresis gels in children with metabolic syndrome. AB - BACKGROUND: The antiatherogenic role of different HDL subclasses is still controversial. HDL particles of the same size can have different lipid contents in some physiopathological situations. However, little is known about the plasma lipid levels of HDL subclasses when they are separated by their hydrodynamic diameter. METHODS: Triglycerides (Tg), phosphatidylcholine (Ph), and cholesterol (C) plasma concentrations of HDL subclasses, were determined by enzymatic staining on polyacrylamide gradient gel (PAGE) in 50 pediatric patients with metabolic syndrome (MS), and 50 control children paired by age and gender. Proteins of HDL subclasses were also stained for the assessment of the relative size distribution of HDL. RESULTS: Relative HDL size distribution was shifted to small particles in MS pediatric patients when determined per protein. In contrast, cholesterol plasma concentrations corresponding to the HDL2b, 2a, 3a, and 3b subclasses were decreased; triglycerides of HDL3b and 3c, as well as plasma phospholipids from HDL3c, were elevated in MS patients as compared to controls. The C-to-Ph ratio, considered as indicative of HDL composition, was similar among the 5 HDL subclasses in control subjects, whereas this ratio gradually decreased from large HDL2b to small HDL3c in the MS group. Cholesterol plasma concentrations of HDL subclasses correlated with the components of the MS. CONCLUSIONS: Lipids of HDL subclasses provide more and accurate information than the relative HDL size distribution determined by protein staining, and may contribute to understand better HDL metabolism and the coronary risk associated to these lipoproteins. PMID- 21036161 TI - Impact of phlebotomy decision support application on sample collection errors and laboratory efficiency. PMID- 21036162 TI - On freeze-thaw sequence of vital organ of assuming the cryoablation for malignant lung tumors by using cryoprobe as heat source. AB - Regarding cryoablation for the malignant lung tumors, multiple trials of the freeze-thaw process have been made, and we considered it necessary to view and analyze the freeze-thaw process as a freeze-thaw sequence. We caused the sequence in a porcine lung in vivo by using an acicular, cylindrical stainless-steel probe as the heat source for the freeze-thaw sequence and cooling to -150 degrees C with super high-pressure argon gas by causing the Joule-Thomson effect phenomenon at the tip of the probe. In this experiment, we examined the sequence by measuring the temperature and using the isothermal curve and the freezing function. As a result, it was demonstrated that the freezing characteristics considerably differed in the first sequence and the second sequence from those of non-aerated organs such as liver and kidney. In our experiments on porcine lung, thermal properties were considered to change as the bleeding caused by the first thawing infiltrated in the lung parenchyma, and it was confirmed that the frozen area in the second cycle was dramatically enlarged as compared with the first cycle (when a similar sequence is continuously repeated, we say it as cycle). This paper provides these details. PMID- 21036163 TI - Somatic stem cells express Piwi and Vasa genes in an adult ctenophore: ancient association of "germline genes" with stemness. AB - Stem cells are essential for animal development and adult tissue homeostasis, and the quest for an ancestral gene fingerprint of stemness is a major challenge for evolutionary developmental biology. Recent studies have indicated that a series of genes, including the transposon silencer Piwi and the translational activator Vasa, specifically involved in germline determination and maintenance in classical bilaterian models (e.g., vertebrates, fly, nematode), are more generally expressed in adult multipotent stem cells in other animals like flatworms and hydras. Since the progeny of these multipotent stem cells includes both somatic and germinal derivatives, it remains unclear whether Vasa, Piwi, and associated genes like Bruno and PL10 were ancestrally linked to stemness, or to germinal potential. We have investigated the expression of Vasa, two Piwi paralogues, Bruno and PL10 in Pleurobrachia pileus, a member of the early diverging phylum Ctenophora, the probable sister group of cnidarians. These genes were all expressed in the male and female germlines, and with the exception of one of the Piwi paralogues, they showed similar expression patterns within somatic territories (tentacle root, comb rows, aboral sensory complex). Cytological observations and EdU DNA-labelling and long-term retention experiments revealed concentrations of stem cells closely matching these gene expression areas. These stem cell pools are spatially restricted, and each specialised in the production of particular types of somatic cells. These data unveil important aspects of cell renewal within the ctenophore body and suggest that Piwi, Vasa, Bruno, and PL10 belong to a gene network ancestrally acting in two distinct contexts: (i) the germline and (ii) stem cells, whatever the nature of their progeny. PMID- 21036164 TI - Doxycycline attenuates acrolein-induced mucin production, in part by inhibiting MMP-9. AB - Matrix metalloproteinases (MMPs), especially MMP-9, have been found to increase the expression of epidermal growth factor (EGF) receptor, a possible regulator of acrolein-induced mucin expression in the airway epithelium. The aim of this study was to investigate whether doxycycline, a tetracycline antibiotic that inhibits MMPs, attenuates mucus production and synthesis of mucin MUC5AC in acrolein exposed rats. Sprague-Dawley rats were exposed to acrolein aerosol [3.0parts/million (ppm), 6h/day, 12days] and they received 20mg/kg doxycycline daily by gavage, beginning two days before exposure to acrolein until the end of the experiment. The production of mucin glycoproteins and expression of the MMP-9 and MUC5AC genes were measured in rat trachea. The increase in levels of MMP-9 mRNA and protein in airway epithelium after acrolein exposure was accompanied by an increase in MUC5AC mRNA expression. Doxycycline significantly prevented these increases in acrolein-induced expression of MMP-9 and MUC5AC and attenuated mucus production in tracheal epithelium. These results indicate that doxycycline attenuated acrolein-induced mucin synthesis, in part by inhibiting expression of MMP-9. Thus doxycycline may have a prophylactic effect in the treatment of smoking-induced mucus hypersecretion. PMID- 21036165 TI - Proteasome inhibitor up regulates liver antioxidative enzymes in rat model of alcoholic liver disease. AB - Oxidative stress occurs in the liver of rats fed with alcohol chronically due to ethanol metabolism by CYP2E1, causing liver injury. The proteasome is considered as an antioxidant defense in the cell because of its activity in removing damaged and oxidized proteins, but a growing body of evidence shows that proteasome inhibitor treatment, at a non toxic low dose, provides protection against oxidative stress. In the present study, rats were fed with ethanol for 4 weeks and were treated with the proteasome inhibitor PS-341 (Bortezomib, Velcade(r)). Exposure to proteasome inhibitor elicited the elevation of antioxidative defense by enhancing the levels of mRNA and protein expression transcripts of glutathione reductase (GSR), glutathione synthetase (GSS), glutathione peroxidase 2 (GPX2), and superoxide dismutase 2 (SOD2) in the liver of rats fed with ethanol chronically, while ethanol alone did not increase these genes' mRNA. Our results also showed that glutamate cysteine ligase catalytic subunit (GCLC), a rate limiting enzyme in glutathione biosynthesis, was also up regulated in the liver of rats fed with ethanol and injected with PS-431. Nrf2 mRNA level was significantly decreased in the liver of ethanol fed rats, as well as in the livers of animal fed with ethanol and treated with proteasome inhibitor, indicating that the mechanism by which proteasome inhibitor up regulates the antioxidant response element is not due to regulation of Nrf2. However, ATF4, a major regulator of antioxidant response elements, was significantly up regulated by proteasome inhibitor treatment. The beneficial effects of proteasome inhibitor treatment also reside in the reversibility of the drug because the proteasome activity was significantly increased 72 h post treatment. In conclusion, proteasome inhibitor treatment used at a non toxic low dose has potential protective effects against oxidative stress due to chronic ethanol feeding. PMID- 21036166 TI - Connexin32 protects against vascular inflammation by modulating inflammatory cytokine expression by endothelial cells. AB - Gap junctions (GJs) play an important role in vascular function, stability, and homeostasis in endothelial cells (ECs), and GJs are comprised of members of the connexin (Cx) family. GJs of vascular ECs are assembled from Cx37, Cx40, and Cx43, and we showed that ECs also express Cx32. In this study, we investigated a potential role for Cx32 during vascular inflammation. Expression of Cx32 mRNA and protein by human umbilical venous ECs (HUVECs) decreased following treatment with tumor necrosis factor (TNF)-alpha, but lipopolysaccharide (LPS) and interleukin (IL)-1beta did not affect Cx32 expression. Intracellular transfer of an inhibitory anti-Cx32 monoclonal antibody significantly enhanced TNF-alpha-induced monocyte chemotactic protein (MCP)-1 and IL-6 expression, but overexpression of Cx32 abrogated TNF-alpha-induced MCP-1 and IL-6 expression. LPS treatment of Cx32 knock-out mice significantly increased the serum concentrations of TNF-alpha, interferon-gamma, IL-6 and MCP-1, compared to wild-type littermate mice. These data suggest that Cx32 protects ECs from inflammation by regulating cytokine expression and plays an important role in the maintenance of vascular function. PMID- 21036167 TI - Tropomyosin isoform 3 promotes the formation of filopodia by regulating the recruitment of actin-binding proteins to actin filaments. AB - Tropomyosins are believed to function in part by stabilizing actin filaments. However, accumulating evidence suggests that fundamental differences in function exist between tropomyosin isoforms, which contributes to the formation of functionally distinct filament populations. We investigated the functions of the high-molecular-weight isoform Tm3 and examined the molecular properties of Tm3 containing actin filament populations. Overexpression of the Tm3 isoform specifically induced the formation of filopodia and changes in actin solubility. We observed alterations in actin-binding protein recruitment to filaments, co incident with changes in expression levels, which can account for this functional outcome. Tm3-associated filaments recruit active actin depolymerizing factor and are bundled into filopodia by fascin, which is both up-regulated and preferentially associated with Tm3-containing filaments in the Tm3 overexpressing cells. This study provides further insight into the isoform-specific roles of different tropomyosin isoforms. We conclude that variation in the tropomyosin isoform composition of microfilaments provides a mechanism to generate functionally distinct filament populations. PMID- 21036168 TI - Importance of syndecan-4 and syndecan -2 in osteoblast cell adhesion and survival mediated by a tissue transglutaminase-fibronectin complex. AB - Tissue transglutaminase (TG2) has been identified as an important extracellular crosslinking enzyme involved in matrix turnover and in bone differentiation. Here we report a novel cell adhesion/survival mechanism in human osteoblasts (HOB) which requires association of FN bound TG2 with the cell surface heparan sulphates in a transamidase independent manner. This novel pathway not only enhances cell adhesion on FN but also mediates cell adhesion and survival in the presence of integrin competing RGD peptides. We investigate the involvement of cell surface receptors and their intracellular signalling molecules to further explore the pathway mediated by this novel TG-FN heterocomplex. We demonstrate by siRNA silencing the crucial importance of the cell surface heparan sulphate proteoglycans syndecan-2 and syndecan-4 in regulating the compensatory effect of TG-FN on osteoblast cell adhesion and actin cytoskeletal formation in the presence of RGD peptides. By use of immunoprecipitation and inhibitory peptides we show that syndecan-4 interacts with TG2 and demonstrate that syndecan-2 and the alpha5beta1 integrins, but not alpha4beta1 function as downstream modulators in this pathway. Using function blocking antibodies, we show activation of alpha5beta1 occurs by an inside out signalling mechanism involving activation and binding of protein kinase PKCalpha and phosphorylation of focal adhesion kinase (FAK) at Tyr(861) and activation of ERK1/2. PMID- 21036169 TI - Molecular identification and expression analysis of lipocalins from blood feeding taiga tick, Ixodes persulcatus Schulze. AB - Lipocalins have been known for their several biological activities in blood sucking arthropods. Recently, the identification and characterization of lipocalins from Ixodes ricinus (LIRs) have been reported and functions of lipocalins are well documented. In this study, we have characterized four Ixodes persulcatus lipocalins that were discovered while analyzing I. persulcatus tick salivary gland EST library. We show that the four I. persulcatus lipocalins, here after named LIPERs (lipocalin from I. persulcatus) are 28.8-94.4% identical to LIRs from I. ricinus. Reverse transcriptase-PCR analysis revealed that lipocalin genes were expressed specifically in the salivary glands throughout life cycle stages of the ticks and were up-regulated by blood feeding. The specific expressions were also confirmed by Western blotting analysis. Furthermore, to investigate whether native lipocalins are secreted into the host during tick feeding, the reactivity of anti-serum raised against saliva of adult ticks to recombinant lipocalins was tested by Western blotting. The lipocalins are potentially secreted into the host during tick feeding as revealed by specific reactivity of recombinant lipocalins with mouse antibodies to I. persulcatus tick saliva. Preliminary vaccination of mice with recombinant lipocalins elicited that period to reach engorgement was significantly delayed and the engorgement weight was significantly reduced as compared to the control. Further elucidation of the biological functions of LIPERs are required to fully understand the pathways involved in the modulation of host immune responses. PMID- 21036170 TI - Trypanosoma evansi: immune response and acetylcholinesterase activity in lymphocytes from infected rats. AB - The existence of cholinergic receptors in the immune system cells is well documented. This study aimed to evaluate the acetylcholinesterase activity (AChE) in lymphocytes from rats infected with Trypanosoma evansi in acute and chronic phase disease. Twenty animals were infected with 10(6) trypomastigotes forms each and 10 were used as negative controls. The two groups of inoculated rats were formed according to the degree of parasitemia and the period post-infection (PI). Group A: rats with 4 days PI and between 24 and 45 parasites/field (1000*); group B: rats with 30 days PI and parasitemia with jagged peaks between 0 and 1 parasites/field; group C: not-infected animals. At 4 days PI (acute phase) and 30 days PI (chronic phase) the rats were anesthetized to collect blood for hemogram and separation of lymphocytes. After separation, the AChE activity was measured in lymphocytes. It was observed that the number of lymphocytes increased significantly in group A compared to group C. The activity of AChE in lymphocytes significantly increased in acute phase and decreased in chronic phase in the infected rats when compared to not-infected (P<0.05). Statistical analysis showed a positive correlation between the number of lymphocytes and AChE activity in lymphocytes in 4 days PI (r(2): 0.59). Therefore, the infection by T. evansi influences AChE activity in lymphocytes of rats indicating changes in the responses of cholinergic system in acute phase, possibly due to immune functions performed by these enzymes. PMID- 21036171 TI - Intraerythrocytic stages of Plasmodium falciparum biosynthesize menaquinone. AB - Herein, we show that intraerythrocytic stages of Plasmodium falciparum have an active pathway for biosynthesis of menaquinone. Kinetic assays confirmed that plasmodial menaquinone acts at least in the electron transport. Similarly to Escherichia coli, we observed increased levels of menaquinone in parasites kept under anaerobic conditions. Additionally, the mycobacterial inhibitor of menaquinone synthesis Ro 48-8071 also suppressed menaquinone biosynthesis and growth of parasites, although off-targets may play a role in this growth inhibitory effect. Due to its absence in humans, the menaquinone biosynthesis can be considered an important drug target for malaria. PMID- 21036172 TI - Identification of a cofilin-like actin-binding site on translationally controlled tumor protein (TCTP). AB - Translationally controlled tumor protein (TCTP) expression is suppressed during cancer cell reversion to a non-malignant phenotype. We identified a primary sequence of TCTP with homology to ADF/cofilin. We confirm that a synthetic peptide corresponding to this sequence binds specifically to actin and is displaced from actin by cofilin. TCTP peptide has higher affinity for G-actin than F-actin and does not block actin-filament depolymerization by cofilin. These results suggest that TCTP may channel active cofilin to F-actin, enhancing the cofilin-activity cycle in invasive tumor cells. Loss of TCTP may result in sequestration of active cofilin by a monomeric pool of actin. PMID- 21036173 TI - The combination of ribavirin and peginterferon is superior to peginterferon and placebo for children and adolescents with chronic hepatitis C. AB - BACKGROUND & AIMS: Although randomized trials of adults infected with hepatitis C virus (HCV) have shown that ribavirin increases the efficacy of pegylated interferon (PEG), such trials have not been performed in children. We conducted a randomized controlled trial of PEG and ribavirin, compared with PEG and placebo, in children 5 to 17 years old with chronic hepatitis C. METHODS: HCV RNA-positive children from 11 university medical centers were randomly assigned to receive either PEG alfa-2a (PEG-2a; 180 MUg/1.73 m(2) body surface area, subcutaneously each week; n = 55) and ribavirin (15 mg/kg orally in 2 doses daily) or PEG-2a and placebo (n = 59) for 48 weeks. The primary end point was sustained virologic response (SVR; lack of detectable HCV RNA at least 24 weeks after stopping therapy). RESULTS: SVR was achieved in 53% of children treated with PEG-2a and ribavirin, compared with 21% of children who received PEG-2a and placebo (P < .001). Early virologic response (HCV RNA reduction >2 log(10) IU at 12 weeks) had a negative predictive value of only 0.89 in children with genotype 1, indicating that these children might benefit from 24 weeks of therapy before stopping treatment. Side effects, especially neutropenia, led to dose modification in 40% of children. Eighty-two percent of the PEG/ribavirin and 86% of the PEG/placebo group were in compliance with the year 2 follow-up visit; the durability of virologic response was 100% in both groups. CONCLUSIONS: The combination of PEG and ribavirin is superior to PEG and placebo as therapy for chronic hepatitis C in children and adolescents. PMID- 21036175 TI - Estrogen biosynthesis in the gonad of the frog Rana rugosa. AB - In certain species of amphibians gonadal differentiation is influenced by steroid hormones. In the case of the frog Rana rugosa testosterone given to tadpoles reverses sex from female to male, while the opposite reversal - male to female - can be achieved using estradiol-17beta. In this study, we investigated whether CYP19 (P450 aromatase), the enzyme responsible for a production of estradiol 17beta, was present in the differentiating gonad of R. rugosa. Initially, we immunized rabbits against frog CYP19 peptides and performed immunostaining using specific antibodies purified from that serum. CYP19-reactive signals were observed in gonadal somatic cells of the female, but not male tadpoles at stage (St.) I (the stage prior to phenotypic sex determination in tadpoles of R. rugosa). Immunopositive signals were also produced in ovarian somatic cells froglets at St. XXV (just after the completion of metamorphosis). We also examined the enzymatic activity of CYP19 in the differentiating gonad of R. rugosa. Reverse-phase HPLC (high performance liquid chromatography) analysis revealed that [(3)H]testosterone was converted to [(3)H]estradiol-17beta in the gonad of tadpoles at St. I. Interestingly, the rate of conversion was much higher in females than in males. To the best of our knowledge, this is the first report on the biosynthesis of estradiol-17beta in the gonad of amphibians, and the co incident identification of active CYP19 enzyme in the differentiating gonad of R. rugosa. Based on our results, we conclude that estradiol-17beta may be involved in ovarian differentiation in this species. PMID- 21036174 TI - The anti-androgen combination, flutamide plus finasteride, paradoxically suppressed LH and androgen concentrations in pregnant spotted hyenas, but not in males. AB - The androgen receptor blocker flutamide and the 5alpha-reductase inhibitor finasteride have been used in a variety of species to investigate the ontogeny of sexual dimorphisms by treating pregnant females or neonates at critical periods of sexual differentiation. Likewise, we have used these drugs to study the profound masculinization of the external genitalia in female spotted hyenas. However, a potential pitfall of administering flutamide, either alone or in combination with finasteride, is that it maintains or even raises plasma concentrations of luteinizing hormone (LH) and testosterone (T), because negative feedback of the hypothalamic-pituitary-gonadal axis is disrupted. Contrary to expectations, when pregnant spotted hyenas were treated with flutamide and finasteride (F&F), the concentrations of T during late gestation were suppressed relative to values in untreated dams. Herein, we further investigate the paradoxical effects of F&F treatment on a battery of sex hormones in spotted hyenas. Beyond the effects on T, we found plasma concentrations of LH, estradiol, progesterone and androstenedione (A4) were also significantly lower in F&F treated pregnant hyenas than in controls. Flutamide and finasteride did not have similar effects on LH, T, and A4 concentrations in male hyenas. The paradoxical effect of F&F treatment on LH and T concentrations in the maternal circulation suggests that negative feedback control of gonadotropin and androgen secretion may be modified in spotted hyenas during pregnancy. PMID- 21036176 TI - Revisiting the evolution of gonadotropin-releasing hormones and their receptors in vertebrates: secrets hidden in genomes. AB - Gonadotropin-releasing hormone (GnRH) and its G protein-coupled receptor, GnRHR, play a pivotal role in the control of reproduction in vertebrates. To date, many GnRH and GnRHR genes have been identified in a large variety of vertebrate species using conventional biochemical and molecular biological tools in combination with bioinformatic tools. Phylogenetic approaches, primarily based on amino acid sequence identity, make it possible to classify these multiple GnRHs and GnRHRs into several lineages. Four vertebrate GnRH lineages GnRH1, GnRH2, GnRH3, and GnRH4 (for lamprey) are well established. Four vertebrate GnRHR lineages have also been proposed-three for nonmammalian GnRHRs and mammalian GnRHR2 as well as one for mammalian GnRHR1. However, these phylogenetic analyses cannot fully explain the evolutionary origins of each lineage and the relationships among the lineages. Rapid and vast accumulation of genome sequence information for many vertebrate species, together with advances in bioinformatic tools, has allowed large-scale genome comparison to explore the origin and relationship of gene families of interest. The present review discusses the evolutionary mechanism of vertebrate GnRHs and GnRHRs based on extensive genome comparison. In this article, we focus only on vertebrate genomes because of the difficulty in comparing invertebrate and vertebrate genomes due to their marked divergence. PMID- 21036177 TI - The influence of thermal environment and food availability on testosterone and gonadal recrudescence in male Chinese skinks [Plestiodon (Eumeces) chinensis]. AB - Most animals show seasonal cycles of reproduction (including cycling of sex steroids). Environmental cues (e.g., temperature) likely play important roles in these seasonal variations but their exact contributions remain unclear. We conducted a two-factor experiment to elucidate the effects of thermal environments and food availability on growth in body mass, testosterone (T) levels and testes morphology in male Chinese skinks [Plestiodon (Eumeces) chinensis]. Skinks in the thermal environment mimicking spring (April) conditions grew slowly but had higher plasma T levels and larger testes with more viable sperms than those in the thermal environment mimicking summer (July) conditions. Skinks exposed to high food treatment grew faster and had higher plasma T levels and more viable sperms than those exposed to low food treatment. Male growth was negatively correlated with reproductive activity as indicated by T levels and testes size. Therefore, both temperature and food availability are important environmental factors that can affect the reproductive cycle of male lizards, and the mechanisms underlying the trade-off between growth and reproduction could involve the regulation of T levels. PMID- 21036178 TI - A new method for rapid detection of T lymphocyte decision to proliferate after encountering activating surfaces. AB - A critical step of the adaptive response is the detection of foreign peptides on antigen presenting cells by T lymphocytes. It is a major challenge for a T lymphocyte to detect the presence of a few tens of cognate ligands or less on the membrane of a cell exposing millions of protein molecules. Detection is followed by the cell decision to undergo full or partial activation or even to start an inhibitory program. While the measurement of cell proliferation or cytokine synthesis is accepted as a reliable means of monitoring T lymphocyte activation, this requires hours or days to complete, which is a significant drawback to relate decision to particular signaling events or to assess lymphocyte reactivity in patients. Here we show that the contact area formed between T lymphocytes and potentially activating surfaces is exquisitely correlated to the proliferative response measured with the standard CFSE technique. Correlation is even better than the Erk activation that was reported as a digital reporter of cell activation. The simple and accurate method of assessing lymphocyte-to-surface contact extension that we describe might be very useful both to monitor lymphocyte reactivity for clinical purposes and to identify early steps of lymphocyte activation. PMID- 21036179 TI - PBAN gene architecture and expression in the fire ant, solenopsis invicta. AB - The PBAN/pyrokinin peptides are a major neuropeptide family characterized by a common FXPRLamide at the C-termini. These peptides are distributed ubiquitously in the Insecta and are involved in many essential endocrine functions, e.g. pheromone production. We report the gene architecture of the fire ant Solenopsis invicta PBAN (Soi-PBAN) gene, including the exon and intron boundaries. Furthermore, we quantified expression of the Soi-PBAN mRNA in the head, thorax and abdomen of the fire ant. The Soi-PBAN gene is comprised three exons and two introns, all composed of 13,358 nucleotides, which is 2-4 times larger than lepidopteran PBAN genes. The overall pattern of the PBAN immunoreactive neuron number and localization was similar for female and male alates, inseminated female delates, workers and queens. The Soi-PBAN mRNA expression level was highest in the head, followed by the thorax, and abdomen of adult ants. Expression in the abdominal tissues was expected to be similar to the head, or at least higher than thorax because strong PBAN immunoreactive neurons were detected previously in brain-subesophageal and abdominal ganglia. This result suggests that another FXPRL gene could be dominant in the abdomen rather than Soi-PBAN gene. PMID- 21036180 TI - Minimal models of growth and decline of microbial populations. AB - Dynamics of growth and decline of microbial populations were analysed and respective models were developed in this investigation. Analysis of the dynamics was based on general considerations concerning the main properties of microorganisms and their interactions with the environment which was supposed to be affected by the activity of the population. Those considerations were expressed mathematically by differential equations or systems of the equations containing minimal sets of parameters characterizing those properties. It has been found that: (1) the factors leading to the decline of the population have to be considered separately, namely, accumulation of metabolites (toxins) in the medium and the exhaustion of resources; the latter have to be separated again into renewable ('building materials') and non-renewable (sources of energy); (2) decline of the population is caused by the exhaustion of sources of energy but no decline is predicted by the model because of the exhaustion of renewable resources; (3) the model determined by the accumulation of metabolites (toxins) in the medium does not suggest the existence of a separate 'stationary phase'; (4) in the model determined by the exhaustion of energy resources the 'stationary' and 'decline' phases are quite discernible; and (5) there is no symmetry in microbial population dynamics, the decline being slower than the rise. Mathematical models are expected to be useful in getting insight into the process of control of the dynamics of microbial populations. The models are in agreement with the experimental data. PMID- 21036181 TI - Autocrine and paracrine up-regulation of blood-brain barrier function by plasminogen activator inhibitor-1. AB - The blood-brain barrier (BBB) is the interface that separates the central nervous system (CNS) from the peripheral circulation. An increase in blood-borne substances including cytokines in plasma and brain affects BBB function, and this is associated with the development of pathogenesis of a number of diseases. Plasminogen activator inhibitor (PAI)-1 regulates the plasminogen activator/plasmin system as a serpin in the periphery and the CNS. We investigated whether PAI-1 alters BBB function using in vitro models of the BBB consisting of rat primary brain endothelial cells (RBECs) alone and co-cultured with pericytes. We found that PAI-1 increased the tightness of the brain endothelial barrier in a time- and dose-dependent manner, as shown by an increase in the transendothelial electrical resistance (TEER) and a decrease in the permeability to sodium fluorescein (Na-F). RBECs responded equally to PAI-1 in the blood-facing and brain-facing sides of the brain, leading to a decrease in Na F permeability. In addition, RBECs constitutively released PAI-1 into the blood facing (luminal) and brain-facing (abluminal) sides. This release was polarized in favor of the luminal side and facilitated by serum. The neutralization of PAI 1 by an antibody to PAI-1 in RBEC/pericyte co-culture more robustly reduced TEER of RBECs than in RBEC monolayers. These findings suggest that PAI-1 derived from the neurovascular unit and peripheral vascular system participates as a positive regulator of the BBB in facilitating the barrier function of the endothelial tight junctions. PMID- 21036183 TI - Multisensory perception of action in posterior temporal and parietal cortices. AB - Environmental events produce many sensory cues for identifying the action that evoked the event, the agent that performed the action, and the object targeted by the action. The cues for identifying environmental events are usually distributed across multiple sensory systems. Thus, to understand how environmental events are recognized requires an understanding of the fundamental cognitive and neural processes involved in multisensory object and action recognition. Here, we investigated the neural substrates involved in auditory and visual recognition of object-directed actions. Consistent with previous work on visual recognition of isolated objects, visual recognition of actions, and recognition of environmental sounds, we found evidence for multisensory audiovisual event-selective activation bilaterally at the junction of the posterior middle temporal gyrus and the lateral occipital cortex, the left superior temporal sulcus, and bilaterally in the intraparietal sulcus. The results suggest that recognition of events through convergence of visual and auditory cues is accomplished through a network of brain regions that was previously implicated only in visual recognition of action. PMID- 21036184 TI - Signaling through the ghrelin receptor modulates hippocampal function and meal anticipation in mice. AB - The ability to predict a particular meal is achieved in part by learned associations with stimuli that predict nutrient availability. Ghrelin is an orexigenic peptide produced by both the gut and brain that rises before anticipated meals and it has been suggested that pre-prandial ghrelin increases may act as a signal to predict meal delivery. Here, we used wild type and ghrelin receptor deficient mice to test the hypothesis that ghrelin signaling is necessary for the processing of emotionally relevant stimuli, spatial learning and habituated feeding responses. We tested spatial and fear-related memory with the Morris water maze and step through passive avoidance tests, respectively and utilized food anticipatory activity to monitor habituated feeding responses following two weeks of a meal feeding paradigm. Our results indicate that ghrelin signaling modulates spatial memory performance and is necessary for the development of food anticipatory activity. Collectively, these results suggest that ghrelin receptor signaling is necessary for adaptations in the anticipatory responses that accompany restricted feeding. PMID- 21036185 TI - Behavioral characterization of A/J and C57BL/6J mice using a multidimensional test: association between blood plasma and brain magnesium-ion concentration with anxiety. AB - Up to 29% of all adults will experience an anxiety-related disorder during their lives. Treatment of these disorders is still difficult and the exact mechanisms and pathways behind anxiety disorders remain to be elucidated. Although evidence exists for genetically based susceptibility of human psychiatric diseases, risk genes have rarely been identified up to now. Inbred mouse strains are, together with the crosses and genetic reference populations derived from them, important tools for the genetic dissection of complex behavioral traits in the mouse. Thus, inbred mouse models of human anxiety may be a potent starting tool to search for candidate genes in mice, which could then via comparative genomics be translated to the human situation. In this paper we investigate whether the A/J and C57BL/6J mouse inbred strains differ in a limited number of motivational systems (anxiety, exploration, memory, locomotion, and social affinity), but especially in anxiety related behavior from each other. Young adult individuals from both genders of A/J and C57BL/6J strains were behaviorally phenotyped using a multidimensional test: the modified hole board. This paradigm basically is a combination of the traditional hole board and the open field test allowing to test for anxiety related avoidance behavior, risk assessment, arousal, exploration, memory, locomotor activity, and social affinity, using just one single test. An acute, aversive stimulus (intra-peritoneal injection with saline) was applied to the animals to test for the robustness of their behavioral phenotype. In addition, presumed physiological indicators for anxiety (circulating glucose, cholesterol, and corticosterone, adrenal tyrosine hydroxylase, and blood plasma and brain magnesium) were investigated. It could be concluded that C57BL/6J and A/J mice differ with respect to almost all tested motivational systems. For some measures, including anxiety-related behavioral parameters, there were clear gender effects. The high-anxiety phenotype of A/J mice could be shown to represent a primary and robust characteristic. Further, blood plasma and brain magnesium levels were significantly correlated with several anxiety-related behavioral parameters. These results emphasize the hypothesized, and possibly causal, association between magnesium status and emotionality. PMID- 21036187 TI - Control of eukaryotic gene expression: gene loops and transcriptional memory. AB - Gene loops are dynamic structures that juxtapose promoter-terminator regions of Pol II-transcribed genes. Although first described in yeast, gene loops have now been identified in yeast and mammalian cells. Looping requires components of the transcription preinitiation complex, the pre-mRNA 30-end processing machinery, and subunits of the nuclear pore complex. Loop formation is transcription dependent, but neither basal nor activated transcription requires looping. Rather, looping appears to affect cellular memory of recent transcriptional activity, enabling a more rapid response to subsequent stimuli. The nuclear pore has been implicated in both memory and looping. Our working model is that loops are formed and/or maintained at the nuclear pore to facilitate hand-off of Pol II form the terminator to the promoter, thereby bypassing Pol II recruitment as the rate-limiting step in reactivation of transcription. Involvement of the nuclear pore also suggests that looping might facilitate mRNA export to the cytoplasm. The technology now exists to test these ideas. PMID- 21036186 TI - Obesity/hyperleptinemic phenotype adversely affects hippocampal plasticity: effects of dietary restriction. AB - Epidemiological studies estimate that greater than 60% of the adult US population may be categorized as either overweight or obese and there is a growing appreciation that obesity affects the functional integrity of the central nervous system (CNS). We recently developed a lentivirus (LV) vector that produces an insulin receptor (IR) antisense RNA sequence (IRAS) that when injected into the hypothalamus selectively decreases IR signaling in hypothalamus, resulting in increased body weight, peripheral adiposity and plasma leptin levels. To test the hypothesis that this obesity/hyperleptinemic phenotype would impair hippocampal synaptic transmission, we examined short term potentiation (STP) and long term potentiation (LTP) in the hippocampus of rats that received the LV-IRAS construct or the LV-Control construct in the hypothalamus (hypo-IRAS and hypo-Con, respectively). Stimulation of the Schaffer collaterals elicits STP that develops into LTP in the CA1 region of hypo-Con rats; conversely, hypo-IRAS rats exhibit STP that fails to develop into LTP. To more closely examine the potential role of hyperleptinemia in these electrophysiological deficits, hypo-IRAS were subjected to mild food restriction paradigms that would either: 1) prevent the development of the obesity phenotype; or 2) reverse an established obesity phenotype in hypo IRAS rats. Both of these paradigms restored LTP in the CA1 region and reversed the decreases in the phosphorylated/total ratio of GluA1 Ser845 AMPA receptor subunit expression observed in the hippocampus of hypo-IRAS rats. Collectively, these data support the hypothesis that obesity impairs hippocampal synaptic transmission and support the hypothesis that these deficits are mediated through the impairment of hippocampal leptin activity. PMID- 21036182 TI - Metabotropic glutamate receptors: from the workbench to the bedside. AB - Metabotropic glutamate (mGlu) receptors were discovered in the mid 1980s and originally described as glutamate receptors coupled to polyphosphoinositide hydrolysis. Almost 6500 articles have been published since then, and subtype selective mGlu receptor ligands are now under clinical development for the treatment of a variety of disorders such as Fragile-X syndrome, schizophrenia, Parkinson's disease and L-DOPA-induced dyskinesias, generalized anxiety disorder, chronic pain, and gastroesophageal reflux disorder. Prof. Erminio Costa was linked to the early times of the mGlu receptor history, when a few research groups challenged the general belief that glutamate could only activate ionotropic receptors and all metabolic responses to glutamate were secondary to calcium entry. This review moves from those nostalgic times to the most recent advances in the physiology and pharmacology of mGlu receptors, and highlights the role of individual mGlu receptor subtypes in the pathophysiology of human disorders. This article is part of a Special Issue entitled 'Trends in neuropharmacology: in memory of Erminio Costa'. PMID- 21036189 TI - Modulation of methylphenidate effects on wheel running and acoustic startle by acute food deprivation in commercially and selectively bred rats. AB - Behavioral effects of the same dose of the same drug can vary in degree and direction between and within individuals. The present study examines behavioral base rates, feeding status, and dispositional differences as sources of inter- and intra-individual heterogeneity in drug response. Modulation of the effects of methylphenidate (MPD) on wheel running and acoustic startle by food deprivation was examined in three experiments. Freely fed or food deprived Harlan Sprague Dawley rats (running study) or rats selectively bred for low (LoS) and high (HiS) saccharin intake (running and startle studies) were given MPD (10 mg/kg) or saline before testing. Overall drug effects and predictors of drug response were assessed. MPD increased running and startle amplitude and disrupted prepulse inhibition; systematic variation among rats of these effects and their modulation by food deprivation was observed. Deprivation-induced running predicted MPD's effect in Harlan SD and LoS rats. Observation of this relationship among commercial rats suggests that acute deprivation sensitivity has utility as a noninvasive marker for drug responses. Its observation in rats selected on a taste phenotype with known correlates points to fruitful avenues of research on stimulant drugs' mechanisms, especially in dopaminergic pathways, and may be relevant to their clinical usage. PMID- 21036188 TI - Hyperphagia induced by sucrose: relation to circulating and CSF glucose and corticosterone and orexigenic peptides in the arcuate nucleus. AB - Sucrose-rich diets compared to starch-rich diets are known to stimulate overeating under chronic conditions. The present study in normal-weight rats established an acute "preload-to-test meal" paradigm for demonstrating sucrose induced hyperphagia and investigating possible mechanisms that mediate this behavioral phenomenon. In this acute paradigm, the rats were first given a small (15 kcal) sucrose preload (30% sucrose) for 30 min compared to an equicaloric, starch preload (25% starch with 5% sucrose) and then allowed to freely consume a subsequent test meal of lab chow. The sucrose preload, when compared to a starch preload equal in energy density and palatability, consistently increased food intake in the subsequent test meal occurring between 60 and 120 min after the end of the preload. Measurements of hormones, metabolites and hypothalamic peptides immediately preceding this hyperphagia revealed marked differences between the sucrose vs starch groups that could contribute to the increase in food intake. Whereas the sucrose group compared to the starch group immediately after the preload (at 10 min) had elevated levels of glucose in serum and cerebrospinal fluid (CSF) along with reduced expressions of neuropeptide Y (NPY) and agouti related protein (AgRP) in the arcuate nucleus (ARC), the subsequent effects (at 30-60 min) just preceding the test meal hyperphagia were the reverse. Along with lower levels of glucose, they included markedly elevated serum and CSF levels of corticosterone and mRNA levels of NPY and AgRP in the ARC. In addition to establishing an animal model for sucrose-induced hyperphagia, these results demonstrate peripheral and central mechanisms that may mediate this behavioral phenomenon. PMID- 21036190 TI - Prolonged treatment with vitamins C and E separately and together decreases anxiety-related open-field behavior and acoustic startle in hooded rats. AB - Adult male and female hooded rats (about 110 days old) consumed vitamins C and E separately and combined together in their drinking water and were assessed for anxiety approximately 50 and then 80 days later in an open field and an acoustic startle apparatus. They were tested when 160+ days old, and then again at 190+ days. For both testing ages combined, the vitamins and their combination increased open-field ambulation and occupancy of the four center squares of the apparatus, while also accordingly decreasing occupancy of the four corners. Treatment with vitamins C and E separately and combined together also decreased acoustic startle amplitude. While there were several significant overall sex and testing age differences, there was no evidence that the vitamin treatment effects were dependent on the operation of either variable. There was also no evidence of synergism between vitamins C and E in their effects. It was suggested that decreases in anxiety produced by the vitamins may have arisen from their antioxidant properties, attenuation of cortisol activity or some as yet undetermined effects on anxiety-related brain structures and neurotransmitters. PMID- 21036191 TI - The predictive validity of the rat self-administration model for abuse liability. AB - The self-administration model is the primary non-clinical approach for assessing the reinforcing properties of novel compounds. Given the now frequent use of rats in self-administration studies, it is important to understand the predictive validity of the rat self-administration model for use in abuse liability assessments. This review of 71 drugs identifies high concordance between findings from rat self-administration studies and two clinical indicators of abuse liability, namely reports of positive subjective-effects and the DEA drug scheduling status. To understand the influence of species on concordance we compare rodent and non-human primate (NHP) self-administration data. In the few instances where discrepancies are observed between rat data and the clinical indicators of abuse liability, rat self-administration data corresponds with NHP data in the majority of these cases. We discuss the influence of genetic factors (sex and strain), food deprivation state and the study design (acquisition or drug substitution) on self-administration study outcomes and highlight opportunities to improve the predictive validity of the self-administration model. PMID- 21036192 TI - The social brain in adolescence: evidence from functional magnetic resonance imaging and behavioural studies. AB - Social cognition is the collection of cognitive processes required to understand and interact with others. The term 'social brain' refers to the network of brain regions that underlies these processes. Recent evidence suggests that a number of social cognitive functions continue to develop during adolescence, resulting in age differences in tasks that assess cognitive domains including face processing, mental state inference and responding to peer influence and social evaluation. Concurrently, functional and structural magnetic resonance imaging (MRI) studies show differences between adolescent and adult groups within parts of the social brain. Understanding the relationship between these neural and behavioural observations is a challenge. This review discusses current research findings on adolescent social cognitive development and its functional MRI correlates, then integrates and interprets these findings in the context of hypothesised developmental neurocognitive and neurophysiological mechanisms. PMID- 21036193 TI - Enhanced mismatch negativity in adolescents with posttraumatic stress disorder (PTSD). AB - The mismatch negativity (MMN) is observed following rare or unique sensory events, and reflects pre-attentional sensory processing of unexpected stimuli. The MMN is altered in several mental illnesses, including post-traumatic stress disorder (PTSD), but did not yield consistent results. We measured MMN in 27 survivors of the Wenchuan earthquake, including 13 who were diagnosed with PTSD, to determine if pre-attentive processing in the auditory cortex was altered by this disease. The amplitude of MMN was significantly greater in the PTSD group compared to the control group. In contrast, no significant group difference was found in the N1 potential, an event-related potential that reflects cortical transmission of sensory information. These results demonstrated an increased sensitivity to deviant stimuli in PTSD that may reflect a chronic state of hyperarousal and hypervigilance in trauma victims. PMID- 21036195 TI - Epidemiology of human rabies in South Africa, 1983-2007. AB - Rabies remains a global public health problem but increasingly so in the developing world. Given a lack of awareness, priority and diagnostic capability, very few developing countries, especially in Africa, report on laboratory confirmed human rabies cases. Here we present a retrospective study on the epidemiology of human rabies in Republic of South Africa for a 25-year period, 1983-2007, based on laboratory confirmed cases. The study highlights the role of the domestic dog as a reservoir and vector of rabies and contrasts this to the almost negligible contribution of wildlife vectors to the overall burden of human rabies in dog rabies endemic areas. From the collective data set, epidemiological aspects that include various features of these human rabies cases as well as failures in or towards the treatment of exposures are reported. Molecular analysis of virus isolates did not identify any additional cases of rabies attributed to infection with the Duvenhage, Lagos bat or Mokola or any other rabies-related viruses. PMID- 21036194 TI - Is HCMV a tumor promoter? AB - Human cytomegalovirus (HCMV) is a beta-herpesvirus that causes persistent infection in humans and can cause severe disease in fetuses and immunocompromised individuals. Although HCMV is not currently causally implicated in human cancer, emerging evidence suggests that HCMV infection and expression may be specifically associated with human malignancies including malignant glioma, colon, and prostate cancer. In addition, multiple investigators have demonstrated that HCMV can dysregulate signaling pathways involved in initiation and promotion of malignancy, including tumor suppressor, mitogenic signaling, inflammatory, immune regulation, angiogenesis and invasion, and epigenetic mechanisms. This review highlights some of the recent evidence that HCMV might play a role in modulating the tumor microenvironment as well as in the initiation and promotion of tumor cells themselves. PMID- 21036197 TI - NTM and NR3C2 polymorphisms influencing intelligence: family-based association studies. AB - Family, twin, and adoption studies have indicated that human intelligence quotient (IQ) has significant genetic components. We performed a low-density genome-wide association analysis with a family-based association test to identify genetic variants influencing IQ, as measured by Wechsler Adult Intelligence Scale full-score IQ (FSIQ). We examined 11,120 single-nucleotide polymorphisms (SNPs) from the Affymetrix GeneChips 10K mapping array genotyped in 292 nuclear families from Genetic Analysis Workshop 14, a subset from the Collaborative Study on the Genetics of Alcoholism (COGA). A replication analysis was performed using part of International Multi-Center ADHD Genetics Project (IMAGE) dataset. Twenty-two SNPs were identified as having suggestive associations with IQ (p<10(-3)) in the COGA sample and eleven of the SNPs were located within known genes. In particular, NTM at 11q25 (rs411280, p = 0.000764) and NR3C2 at 4q31.1 (rs3846329, p = 0.000675) were two novel genes which have not been associated with IQ in other studies. It has been reported that NTM might play a role in late-onset Alzheimer disease while NR3C2 may be associated with cognitive function and major depression. The associations of these two genes were well-replicated by single-marker and haplotype analyses in the IMAGE sample. In conclusion, our findings provide evidence that chromosome regions of 11q25 and 4q31.1 contain genes affecting IQ. This study will serve as a resource for replication in other populations. PMID- 21036196 TI - The human parental brain: in vivo neuroimaging. AB - Interacting parenting thoughts and behaviors, supported by key brain circuits, critically shape human infants' current and future behavior. Indeed, the parent infant relationship provides infants with their first social environment, forming templates for what they can expect from others, how to interact with them and ultimately how they go on to themselves to be parents. This review concentrates on magnetic resonance imaging experiments of the human parent brain, which link brain physiology with parental thoughts and behaviors. After reviewing brain imaging techniques, certain social cognitive and affective concepts are reviewed, including empathy and trust-likely critical to parenting. Following that is a thorough study-by-study review of the state-of-the-art with respect to human neuroimaging studies of the parental brain-from parent brain responses to salient infant stimuli, including emotionally charged baby cries and brief visual stimuli to the latest structural brain studies. Taken together, this research suggests that networks of highly conserved hypothalamic-midbrain-limbic-paralimbic cortical circuits act in concert to support parental brain responses to infants, including circuits for limbic emotion response and regulation. Thus, a model is presented in which infant stimuli activate sensory analysis brain regions, affect corticolimbic limbic circuits that regulate emotional response, motivation and reward related to their infant, ultimately organizing parenting impulses, thoughts and emotions into coordinated behaviors as a map for future studies. Finally, future directions towards integrated understanding of the brain basis of human parenting are outlined with profound implications for understanding and contributing to long term parent and infant mental health. PMID- 21036198 TI - Persistent psychosis after ingestion of a single tablet of '2C-B'. PMID- 21036199 TI - Analysis of different types of poisoning in a tertiary care hospital in rural South India. AB - The global problem of acute poisoning has steadily increased over the past few years. It is an important cause of morbidity and mortality in developing countries. Better preventive and management strategies can be developed if the incidence and pattern of acute poisoning is known. The study aims at analyzing the pattern, cause and mortality rate of poisoning. The study was conducted in a rural area in South India. This retrospective study was conducted from January 2003-December 2003. The data was analysed using descriptive statistics. Out of the 225 cases 139 were males and 86 females. Poisoning was common in the age group of 21-30 years which was 84 cases and 11-20 years was 73 cases. The poisons consumed were as follows: Organophosphorous 135 cases, aluminum and zinc phosphide 50 cases, phenobarbitone 18 cases, benzodiazepines 7 cases, paracetamol 2 cases, miscellaneous 13 cases. 94% were suicides and 6% accidental. Mortality rate was 12.8%. Establishment of strict policies against the sale and availability of pesticides and over the counter drugs is an effective way to control organophosphorous and drug poisoning. PMID- 21036200 TI - Time course of affective processing bias in major depression: An ERP study. AB - The current study investigated the time course of the affective processing bias in major depressive disorder (MDD) in a visual three-stimulus semantic oddball task using event-related potentials (ERPs). MDD patients showed decreased P1 latency over right posterior regions to negative relative to positive target stimuli, reflecting a very early onset of the negativity bias in emotional perception. Compared to controls, MDD patients showed enlarged anterior P2 amplitude to positive target stimuli, reflecting an affective bias in the early attentional stages of processing. In addition, MDD patients showed relatively high N2 and reduced P3 amplitudes to negative compared with positive target stimuli, as well as marginally reduced N2 amplitude to positive target stimuli compared with controls. This suggests that the negativity bias also occurs during later strategic evaluation stages. Therefore, the present study extended previous findings by demonstrating that the affective processing bias in MDD begins in the early stages of perceptual processing and continues at later cognitive stages. PMID- 21036201 TI - Theta burst stimulation of dorsolateral prefrontal cortex modulates pathological language switching: A case report. AB - Although different lesion and neuroimaging studies had highlighted the importance of the dorsolateral prefrontal cortex (DLPFC) in language switching, the nature of this higher cortical disorder of communication and its neural correlates have not been clearly established. To further investigate the functional involvement of the DLPFC, we used transcranial magnetic stimulation (TMS) given as theta burst stimulation (TBS) in a bilingual patient showing pathologic language switching after an ischemic stroke involving the left frontal lobe. Inhibitory and excitatory TBS were applied to the left DLPFC, to the right DLPFC, or to an occipital cortical control site. A short-lasting interruption of the pathological language switching occurred after excitatory left DLPFC stimulation, while inhibitory left DLPFC TBS transiently increased the number of utterances produced in the unwanted second language. Effects were non-significant after right DLPFC and occipital TBS. Our findings suggest that left DLPFC is actively involved in language switching. TMS techniques may help in understanding the neural bases of bilingualism. PMID- 21036202 TI - Estrogen-induced reactive oxygen species-mediated signalings contribute to breast cancer. AB - Elevated lifetime estrogen exposure is a major risk factor for breast cancer. Recent advances in the understanding of breast carcinogenesis clearly indicate that induction of estrogen receptor (ER) mediated signaling is not sufficient for the development of breast cancer. The underlying mechanisms of breast susceptibility to estrogen's carcinogenic effect remain elusive. Physiologically achievable concentrations of estrogen or estrogen metabolites have been shown to generate reactive oxygen species (ROS). Recent data implicated that these ROS induced DNA synthesis, increased phosphorylation of kinases, and activated transcription factors, e.g., AP-1, NRF1, E2F, NF-kB and CREB of non-genomic pathways which are responsive to both oxidants and estrogen. Estrogen-induced ROS by increasing genomic instability and by transducing signal through influencing redox sensitive transcription factors play important role (s) in cell transformation, cell cycle, migration and invasion of the breast cancer. The present review discusses emerging data in support of the role of estrogen induced ROS-mediated signaling pathways which may contribute in the development of breast cancer. It is envisioned that estrogen induced ROS mediated signaling is a key complementary mechanism that drives the carcinogenesis process. ROS mediated signaling however occurs in the context of other estrogen induced processes such as ER-mediated signaling and estrogen reactive metabolite-associated genotoxicity. Importantly, estrogen-induced ROS can function as independent reversible modifiers of phosphatases and activate kinases to trigger the transcription factors of downstream target genes which participate in cancer progression. PMID- 21036203 TI - Spatial and emotional memory in aged rats: a behavioral-statistical analysis. AB - Age-related impairment in synaptic plasticity, like long-term potentiation (LTP), has been repeatedly reported. We had shown that late stages of LTP in the rat dentate gyrus can be modulated by emotional factors, but this is impaired by aging. In the present study we have searched for possible impairments in emotional and spatial memory tasks that may correspond to the impaired reinforcement observed at the cellular level. We have trained young and aged animals in a battery of tests: exploration (open field) object recognition, anxiety (plus maze) fear conditioning and spatial memory (Morris' water maze (MWM)). The open field, anxiety, and novelty recognition showed no age differences except a reduced velocity in aged rats. Emotional and contextual memories were preserved, but acquisition was slightly impaired. Age-dependent impairments appeared in spatial memory, evaluated in terms of latency and distance to reach the hidden escape platform in the water maze task, but these were not related with impairments in other tests, in particular there was no relation between spatial and emotional memory impairments. Age-related impairments in different paradigms were caused by different independent factors that did not correlated with each other. PMID- 21036204 TI - Medial prefrontal cortex receives input from dorsal raphe nucleus neurons targeted by hypocretin1/orexinA-containing axons. AB - The medial prefrontal cortex (mPFC) is strongly involved in cognition and behavior. It receives input from brainstem nuclei implicated in behavioral wakefulness and electrographic cortical activation, such as the dorsal raphe nucleus (DRN). Moreover, the hypocretinergic/orexinergic (Hcrt/Ox) hypothalamic neurons innervate DRN, thus modulating its activity and presumably allowing transitions between sleep-wakefulness cycle states. Dysfunction in this system is associated with narcolepsy. In this study we aimed to determine the precise location of DRN neurons projecting to mPFC and the extent to which they contain serotonin (5-hydroxytryptamine); we have also assessed whether Hcrt1/OxA neurons innervate DRN neurons that could sustain behavioral wakefulness through their projections to mPFC. The retrograde tracer Fluorogold was injected into mPFC and DRN sections were processed for double immunolabeling of anti-Fluorogold and either anti-5-hydroxytryptamine or anti-Hcrt1/OxA antisera. Most DRN neurons projecting to mPFC were located in the ventral sector of the rostral and intermediate DRN, and around half of them were serotonergic. Hcrt1/OxA immunoreactivity in DRN was observed in unmyelinated axons and axon boutons (varicosities or axon terminals). Hcrt1/OxA immunoreactivity was observed within the cytoplasm and in dense-cored vesicles of these axons. Hcrt1/OxA-labeled boutons established both asymmetric synapses (n=30) and appositional contacts (n=102) with Fluorogold-labeled dendrites belonging to DRN neurons projecting to mPFC. Our results show that Hcrt1/OxA neurons may exert a direct synaptic influence on DRN neurons that could facilitate wakefulness, although other non synaptic actions through volume transmission are also suggested. PMID- 21036205 TI - Presbyopic intraocular lenses for monocular cataract. PMID- 21036206 TI - Ocular pathogens for the twenty-first century. PMID- 21036207 TI - Flexibility and presbyopia intraocular lenses. PMID- 21036208 TI - Causation in epidemiology. PMID- 21036209 TI - Recent outbreaks of atypical contact lens-related keratitis: what have we learned? AB - PURPOSE: To examine the public health implications of 2 recent outbreaks of atypical contact lens-related infectious keratitis. DESIGN: Perspective based on the literature and authors' experience. RESULTS: The contact lens-related Fusarium and Acanthamoeba keratitis outbreaks were each detected by dramatic rises seen in tertiary care centers in Singapore and the United States, respectively. Case-control studies of both outbreaks were able to identify a strong association with the use of different contact lens disinfection solutions. Their respective recalls resulted in a steep decline of Fusarium keratitis, but not of Acanthamoeba keratitis. Early investigations into each solution association implicated components not directly related to their primary disinfectant, but the true pathogenesis remains unknown. However, the number of Acanthamoeba cases individually attributed to each of almost all available disinfection systems exceeds the previously understood total United States incidence, suggesting other risk factors. Current standards do not require demonstration of anti-acanthamoebal activity. Yet, despite the inclusion of Fusarium in mandatory testing for solutions, current premarket testing was not predictive of the outbreak. CONCLUSIONS: The 2 recent outbreaks of atypical contact lens-related keratitis have reinforced the value of tertiary care eye care centers in detecting early rises in rare infections and the power of adaptable, well-designed epidemiologic investigations. Although Fusarium keratitis has declined significantly with the recall of Renu with MoistureLoc (Bausch & Lomb Inc.), the persistence of Acanthamoeba keratitis demands fundamental changes in contact lens hygiene practices, inclusion of Acanthamoeba as a test organism, and contact lens disinfectant test regimens for all contact lens-related pathogens that are verifiably reflective of end user contact lens wear complications. PMID- 21036211 TI - Choroidal neovascularization in pathologic myopia. PMID- 21036212 TI - Preoperative subpterygeal mitomycin C injection. PMID- 21036213 TI - Photodynamic therapy for polypoidal choroidal vasculopathy. PMID- 21036217 TI - Retrocorneal membranes: a comparative immunohistochemical analysis of keratocytic, endothelial, and epithelial origins. PMID- 21036218 TI - Demonstration of efficacy in the treatment of dry eye disease with 0.18% sodium hyaluronate ophthalmic solution (vismed, rejena). PMID- 21036221 TI - Sympathetic ophthalmia in Operation Iraqi Freedom. PMID- 21036220 TI - Outcomes and complications of rhegmatogenous retinal detachment repair with selective sutureless 25-gauge pars plana vitrectomy. PMID- 21036223 TI - Methods to assess the mechanism of protein function. Preface. PMID- 21036225 TI - Detecting constitutive activity and protean agonism at cannabinoid-2 receptor. AB - Since the cannabinoid system is involved in regulating several physiological functions such as locomotor activity, cognition, nociception, food intake, and inflammatory reaction, it has been the subject of intense study. Research on the pharmacology of this system has enormously progressed in the last 20years. One intriguing aspect that emerged from this research is that cannabinoid receptors (CBs) express a high level of constitutive activity. Investigation on this particular aspect of receptor pharmacology has largely focused on CB1, the CB subtype highly expressed in several brain regions. More recently, research on constitutive activity on the other CB subtype, CB2, was stimulated by the increasing interest on its potential as target for the treatment of various pathologies (e.g., pain and inflammation). There are several possible implications of constitutive activity on the therapeutic action of both agonists and antagonists, and consequently, it is important to have valuable methods to study this aspect of CB2 pharmacology. In the present chapter, we describe three methods to study constitutive activity at CB2: two classical methods relying on the detection of changes in cAMP level and GTPgammaS binding and a new one based on cell impedance measurement. In addition, we also included a section on detection of protean agonism, which is an interesting pharmacological phenomenon strictly linked to constitutive activity. PMID- 21036224 TI - Constitutive activity at the cannabinoid CB(1) receptor and behavioral responses. AB - The cannabinoid receptor type 1, found mainly on cells of the central and peripheral nervous system, is a major component of the endogenous cannabinoid system. Constitutive and endogenous activity at cannabinoid receptor type 1 regulates a diverse subset of biological processes including appetite, mood, motor function, learning and memory, and pain. The complexity of cannabinoid receptor type 1 activity is not limited to the constitutive activity of the receptor: promiscuity of ligands associated with and the capability of this receptor to instigate G protein sequestration also complicates the activity of cannabinoid receptor type 1. The therapeutic use of cannabinoid receptor type 1 agonists is still a heavily debated topic, making research on the mechanisms underlying the potential benefits and risks of cannabinoid use more vital than ever. Elucidation of these mechanisms and the quest for agonists and antagonists with greater specificity will allow a greater control of the side effects and risks involved in utilizing cannabinoids as therapeutic agents. In this chapter, we review a small subset of techniques used in the pharmacological application of and the behavioral effects of molecules acting at the paradoxical cannabinoid receptor type 1. PMID- 21036226 TI - Modulation of the constitutive activity of the ghrelin receptor by use of pharmacological tools and mutagenesis. AB - Ghrelin and its receptor are important regulators of metabolic functions, including appetite, energy expenditure, fat accumulation, and growth hormone (GH) secretion. The ghrelin receptor is characterized by an ability to signal even without any ligand present with approximately 50% of the maximally ghrelin induced efficacy-a feature that may have important physiological implications. The high basal signaling can be modulated either by administration of specific ligands or by engineering of mutations in the receptor structure. [D-Arg(1), D Phe(5), D-Trp(7,9), Leu(11)]-substance P was the first inverse agonist to be identified for the ghrelin receptor, and this peptide has been used as a starting point for identification of the structural requirements for inverse agonist properties in the ligand. The receptor binding core motif was identified as D-Trp Phe-D-Trp-Leu-Leu, and elongation of this peptide in the amino-terminal end determined the efficacy. Attachment of a positively charged amino acid was responsible for full inverse agonism, whereas an alanin converted the peptide into a partial agonist. Importantly, by use of mutational mapping of the residues critical for the modified D-Trp-Phe-D-Trp-Leu-Leu peptides, it was found that space-generating mutations in the deeper part of the receptor improved inverse agonism, whereas similar mutations located in the more extracellular part improved agonism. Modulation of the basal signaling by mutations in the receptor structure is primarily obtained by substitutions in an aromatic cluster that keep TMs VI and VII in close proximity to TM III and thus stabilize the active conformation. Also, substitution of a Phe in TM V is crucial for the high basal activity of the receptor as this residue serves as a partner for Trp VI:13 in the active conformation. It is suggested that inverse agonist and antagonist against the ghrelin receptor provide an interesting possibility in the development of drugs for treatment of obesity and diabetes and that improved structural understanding of the receptor function facilitates the drug development. PMID- 21036227 TI - Assessment of constitutive activity and internalization of GPR54 (KISS1-R). AB - The kisspeptin/GPR54 signaling system positively regulates GnRH secretion, thereby acting as an important regulator of the hypothalamic-pituitary-gonadal axis. It also negatively regulates tumor metastases and placental trophoblast invasion. GPR54 is a G(q/11)-coupled GPCR and activation by kisspeptin stimulates PIP(2) hydrolysis and inositol phosphate (IP) formation, Ca(2+) mobilization, arachidonic acid release, and ERK1/2 and p38 MAP kinase phosphorylation. Recently, we reported that GPR54 displays constitutive activity and internalization in the heterologous human embryonic kidney 293 cell system. Given the physiological and clinical importance of GPR54 as well as other GPCRs, we present assays for measuring constitutive receptor internalization and activity. Specifically, we describe the use of immunofluorescence coupled to confocal imaging, flow cytometry and indirect receptor radiolabeling to measure constitutive receptor internalization, and IP turnover in intact cells to measure constitutive activity. While we use the FLAG-tagged GPR54 molecule as an example to describe these assays, the assays can be applied to a wide range of GPCRs. PMID- 21036228 TI - Assessment of constitutive activity in E-type prostanoid receptors. AB - The potential for G-protein-coupled receptors (GPCRs) to show constitutive activity is emerging as one of the fundamental properties of GPCRs signal transduction. Indeed, of the four subtypes of E-type prostanoid (EP) receptors, the EP3 and EP4 subtypes show constitutive activity in addition to their innate ligand-dependent activation of signaling pathways. The constitutive activity of the EP3 and EP4 receptor subtypes was discovered during the initial characterizations of these receptors and may be important for setting the basal level of cellular tone in the given signaling pathway. This chapter introduces some of the methods that can be used to study the constitutive activity of the EP receptors. PMID- 21036229 TI - alpha(1D)-Adrenergic receptors constitutive activity and reduced expression at the plasma membrane. AB - Adrenergic receptors are a heterogeneous family of the G protein-coupled receptors that mediate the actions of adrenaline and noradrenaline. Adrenergic receptors comprise three subfamilies (alpha(1), alpha(2), and beta, with three members each) and the alpha(1D)-adrenergic receptor is one of the members of the alpha(1) subfamily with some interesting traits. The alpha(1D)-adrenergic receptor is difficult to express, seems predominantly located intracellularly, and exhibits constitutive activity. In this chapter, we will describe in detail the conditions and procedures used to determine changes in intracellular free calcium concentration which has been instrumental to define the constitutive activity of these receptors. Taking advantage of the fact that truncation of the first 79 amino acids of alpha(1D)-adrenergic receptors markedly increased their membrane expression, we were able to show that constitutive activity is present in receptors truncated at the amino and carboxyl termini, which indicates that such domains are dispensable for this action. Constitutive activity could be observed in cells expressing either the rat or human alpha(1D)-adrenergic receptor orthologs. Such constitutive activity has been observed in native rat arteries and we will discuss the possible functional implications that it might have in the regulation of blood pressure. PMID- 21036230 TI - Constitutive activity of the histamine H(1) receptor. AB - The histamine H(1) receptor (H(1)R) is a key player in acute inflammatory responses. Antihistamines are widely used to relief the symptoms of allergic rhinitis by antagonizing histamine binding to the H(1)R, without possessing intrinsic activity in classical assays such as guinea pig ileum contraction assays or intracellular Ca(2+) mobilization. Overexpression of H(1)R in heterologous cell lines unmasked the capacity of this receptor to signal in a histamine-independent manner. Moreover, a recent screen of therapeutic and reference antagonists on these H(1)R-overexpressing cells revealed that the majority of these drugs are in fact inverse agonists, as they inhibit basal H(1)R activity. In this chapter, we describe several approaches to study H(1)R constitutive signaling that can be used to identify inverse agonists acting at this blockbuster target. PMID- 21036231 TI - Constitutive activity of somatostatin receptor subtypes. AB - The five somatostatin receptors (SSTR1-5) are G-protein-coupled receptors, coupling to G(alphai/0) subunits to regulate pathways including inhibiting adenylate cyclase activity and reduce intracellular cAMP levels and decrease intracellular calcium levels. In the pituitary gland, somatostatin actions, mediated through SSTR1, 2, 3, and 5, are inhibition of growth hormone, thyrotropin hormone, and adrenocorticotropin hormone release and to a lesser extent, inhibition of cell growth. Establishment of constitutive SSTRs action suggests that abundant pituitary SSTR expression contributes to pituitary function in maintaining homeostasis, aside from the SSTR response to episodic hypothalamic somatostatin release. In this chapter, we describe an experimental approach to directly and indirectly demonstrate constitutive SSTR activity by altering receptor density in AtT20 mouse pituitary corticotroph tumor cells, utilizing small interference RNA to knock receptor expression down or stable SSTRs transfection to overexpress selective receptor levels. We describe methodical validation for each of the approaches and the use of a sensitive cAMP assay to analyze consequences of changing membrane receptor number in the absence of an added ligand. PMID- 21036232 TI - Assessment of homologous internalization of constitutively active N111G mutant of AT(1) receptor. AB - Constitutively active mutants (CAMs) of G-protein-coupled receptors mimic the active conformation of the receptor in their ability to activate second messenger systems in the absence of agonist. They have revealed novel properties of drugs that reverse the basal levels of constitutive activity, indicating that the drugs have the inverse agonist activity. Internalization plays an important role in receptor endocytosis and signal transduction. The present chapter provides the investigation of the internalization behavior of CAM N111G of Angiotensin II type 1 (AT(1)) receptor and correlates the result with the mechanism of constitutive activity of the mutant. Both wild-type (WT) and N111G mutant receptors were transiently expressed in COS-7 cells and total inositol phosphate production was measured in presence and absence of the angiotensin II receptor blockers (ARBs). The binding affinities toward agonist and ARBs were also determined. We found that the ARBs have the inverse agonist activity in CAM N111G of AT(1) receptor. The internalization of the mutant, which was much lower than WT receptor, was significantly increased in presence of the ARBs. The results indicate that internalization of CAM N111G of AT(1) receptor is induced by the ARBs, which may be an important characteristic of inverse agonist activities of the ARBs in N111G. PMID- 21036233 TI - Methods to detect cell surface expression and constitutive activity of GPR6. AB - GPR6 is a constitutively active Gs-coupled receptor that can signal from intracellular compartments. We present different methods used to study cell surface expression of receptors and other membrane proteins. A comparison of these methods shows that methods based on susceptibility to proteolytic enzymes are more efficient at providing estimates of cell surface expression than the commonly used cell surface biotinylation method. We also present different methods that can be used to detect constitutive activity of Gs-coupled receptors. Imaging-based assays to detect intracellular cyclic AMP accumulation are well suited to study signaling at a single cell level. These assays are particularly useful when the cells of interest form a small fraction of the culture such as primary cultures with low transfection efficiency. PMID- 21036234 TI - beta(3)-Adrenoceptor agonists and (antagonists as) inverse agonists history, perspective, constitutive activity, and stereospecific binding. AB - beta(3)-Adrenergic receptor (beta(3)-AR) is expressed in several tissues and is considered a drug target for the treatment of several pathologies such as obesity, type 2 diabetes, cachexia, metabolic syndrome, heart failure, anxiety and depressive disorders, preterm labor, overactive bladder, control colon motility, and of coadjuvants in colon cancer therapy. It is a seven-transmembrane domain (7TD) G-protein coupled receptor and is usually coupled to a Gs-protein (Gi-protein in very few cases), and its stimulation increases the production of cAMP. A lot of beta(3)-AR agonists have been uncovered and extensively characterized. Conversely, very little is known about beta(3)-AR inverse agonists that would suppress the agonist-independent activity (constitutive activity) of the receptor by stabilizing it in its inactive state. This chapter attempts to outline (a) the importance of the beta(3)-AR as a therapeutic target through the disquisition of its role in human health (physiology) and disease (pathology); (b) the description of beta(3)-AR structure [amino acid sequence and 7TD organization]; (c) the medicinal chemistry of beta(3)-AR: 7TD amino acid-ligand specific interactions, beta-adrenoreceptor subtype selectivity, stereospecific interactions and biological activity relationships, inverse agonism and blockage of beta(3)-adrenoceptor constitutive activity; and (d) beta(3)-AR inverse agonists. The detailed procedure to prepare and assess the biological activity/selectivity of the more potent and selective beta(3)-AR inverse agonists (SP-1e and SP-1g) up to now known is also described. PMID- 21036235 TI - Constitutive activity of the lutropin receptor and its allosteric modulation by receptor heterodimerization. AB - The lutropin receptor (LHR) is a G protein-coupled receptor (GPCR) that mediates the actions of pituitary LH in males and females and that of placental hCG in pregnant women and, therefore, plays an essential role in reproductive physiology. Mutations of the lhcgr gene that result in constitutive activation of the LHR have been shown to be causative of gonadotropin-independent precocious puberty in young boys. Studies on constitutively active mutants (CAMs) of the LHR have been extremely informative in elucidating the roles of the LHR in reproductive physiology as well as in understanding the molecular basis underlying activation of this GPCR. The constitutive activities of hLHR CAMs can be attenuated by introducing mutations into the CAMs that stabilize the resting state of the hLHR or by coexpressing the hLHR CAMs with an hLHR mutant that is stabilized in the resting state, allowing the two forms of the hLHR to heterodimerize. This chapter describes the experimental methods and strategies underlying studies of hLHR CAMs. PMID- 21036236 TI - Assessing constitutive activity of extracellular calcium-sensing receptors in vitro and in bone. AB - Constitutive activity of the extracellular calcium-sensing receptor (CaSR) has been studied in kindreds with the human disorder autosomal dominant hypocalcemia (ADH) and in an animal model called the Nuf mouse. These families generally showed reduced parathyroid hormone (PTH) secretion and excessive renal calcium (Ca(2+)) excretion. Soft tissues calcifications in the kidney and basal ganglia are frequent (10-50% of ADH cases), and there is a single report of skeletal abnormalities in a family resulting in short stature and premature osteoarthritis. In the latter, a causative mechanism could not be determined. The phenotype of the Nuf mouse is one of ectopic calcifications and cataracts in addition to biochemical abnormalities (low serum Ca(2+) and high serum phosphate concentrations). To better understand the role of CaSRs in the control of osteoblastic function, we generated a transgenic mouse model with constitutively active CaSRs in mature osteoblasts. An analysis of the skeletal phenotype of that mouse indicates that strong signaling by CaSRs in this cell lineage induces alterations in the bone homeostasis reflected in mild osteopenia in male and female mice during growth and in adulthood. These studies indicate that this approach can be readily adapted to assess CaSR actions in other cell systems. PMID- 21036237 TI - Constitutive activity of neural melanocortin receptors. AB - The two neural melanocortin receptors (MCRs), melanocortin-3 and -4 receptors (MC3R and MC4R), are G protein-coupled receptors expressed primarily in the brain that regulate different aspects of energy homeostasis. The MCRs are unique in having endogenous antagonists, agouti and agouti-related protein (AgRP). These antagonists were later shown to be inverse agonists. The MC3R has little or no constitutive activity, whereas the MC4R has significant constitutive activity that can easily be detected. We describe herein methods for detecting constitutive activities in these receptors and small molecule ligands as inverse agonists. AgRP is an inverse agonist for both MC3R and MC4R. We also provide models for the constitutively active MC4R mutants. PMID- 21036238 TI - Measurement of constitutive activity of BMP type I receptors. AB - Bone morphogenetic proteins (BMPs) are pleiotropic cytokines controlling a multitude of processes, among which bone formation. BMPs function by binding and activating BMP type I and type II receptors, resulting in activation of Smad transcription factors and expression of BMP target genes. Mutations in the BMP type I receptor ALK2 were identified in patients suffering from Fibrodysplasia Ossificans Progressiva (FOP). The mutation found in all patients displaying classical FOP symptoms, the ALK2 R206H mutation, renders ALK2 constitutively active. Here, we provide a detailed description of how to determine whether other ALK2 mutations will confer constitutive activity to the receptor. PMID- 21036239 TI - Probing the constitutive activity among dopamine D1 and D5 receptors and their mutants. AB - Dopamine D1 and D5 receptors are prototypical cell-surface seven-transmembrane (TM) G protein-coupled receptors (GPCRs) mediating elevation of intracellular cAMP levels. The high level of constitutive activity of D5 receptor mediating intracellular cAMP production is one of the functional hallmarks distinguishing the closely related D1-like dopaminergic subtypes (D1 and D5). D1-like subtypes share over 80% identity within their TM regions. Thus, D1 and D5 receptors can serve as unparalleled and useful molecular tools to gain structural and mechanistic insights into subtype-specific determinants regulating GPCR constitutive activation and inverse agonism. A method has been developed that relies on the use of transfected human embryonic kidney 293 cells with wild-type (WT), epitope-tagged, chimeric, truncated, and mutant forms of mammalian D1 and D5 receptors using a modified DNA and calcium phosphate precipitation procedure. Receptor expression levels are quantified by a radioligand binding using [(3)H] SCH23390, a D1-like selective drug. Regulation of ligand-independent and dependent activity of WT and mutated D1 and D5 receptors is determined by whole cell cAMP assays using metabolic [(3)H]-adenine labeling and sequential purification radiolabeled nucleotides over Dowex and alumina resin columns. Results on the regulation of D1 and D5 constitutive activity are presented here. Our studies indicate that dopamine-mediated D5 receptor stimulation in a dose dependent manner is not always detectable, suggesting that D5 receptors can exist in a "locked" constitutively activated state. This "locked" constitutively active state of D5 receptor is not linked to aberrant high receptor expression levels or cell behavior, as D1 receptor function remains essentially unchanged in these cells. In fact, we show that phorbol ester treatment of cells harboring "locked" constitutively active D5 receptors abrogates constitutive activation of D5R to allow its stimulation by dopamine in a dose-dependent manner. PMID- 21036240 TI - Identification of gain-of-function variants of the human prolactin receptor. AB - There is currently no known genetic disease linked to prolactin (PRL) or its receptor (PRLR) in humans. Recently, we identified three missense variants of the PRLR in patients presenting with breast tumors. Two of them (named PRLR(I146L) and PRLR(I76V)) had been reported earlier, but failed to draw much attention because the eventual impact of these substitutions on receptor properties remained unknown. In this chapter, we describe the various bioassays (cell types and readouts) that led to the discovery that both variants exhibit gain-of function properties. Reconstituted cell models involving Ba/F3, HEK293, and MCF-7 cell lines all highlighted the constitutive, PRL-independent potency of PRLR(I146L) to trigger downstream signaling, leading to antiapoptotic and proliferation properties. The lower level of basal activity of PRLR(I76V) could be demonstrated only in the very sensitive Ba/F3 cell assay. While comparative analysis of ligands is a routine procedure in many labs, comparison of receptor variants de facto imposes the use of different cell clones (or population) in which each receptor variant is expressed individually. This is more delicate, as one must ensure that differences in biological responses really reflect differences in the intrinsic properties of receptor variants, and not any feature of cell clones/populations that are used, which could bias the interpretation. PMID- 21036241 TI - Investigations of activated ACVR1/ALK2, a bone morphogenetic protein type I receptor, that causes fibrodysplasia ossificans progressiva. AB - Bone morphogenetic protein (BMP) type I receptors are serine-threonine kinase transmembrane signal transduction proteins that regulate a vast array of ligand dependent cell-fate decisions with temporal and spatial fidelity during development and postnatal life. A recent discovery identified a recurrent activating heterozygous missense mutation in a BMP type I receptor [Activin receptor IA/activin-like kinase 2 (ACVR1; also known as ALK2)] in patients with the disabling genetic disorder fibrodysplasia ossificans progressiva (FOP). Individuals with FOP experience episodes of tissue metamorphosis that convert soft connective tissue such as skeletal muscle into a highly ramified and disabling second skeleton of heterotopic bone. The single nucleotide ACVR1/ALK2 mutation that causes FOP is one of the most specific disease-causing mutations in the human genome and to date the only known inherited activating mutation of a BMP receptor that causes a human disease. Thus, the study of FOP provides the basis for understanding the clinically relevant effects of activating mutations in the BMP signaling pathway. Here we briefly review methodologies that we have applied to studying activated BMP signaling in FOP. PMID- 21036242 TI - Identification and evaluation of constitutively active thyroid stimulating hormone receptor mutations. AB - Thyroid stimulating hormone receptor (TSHR) is a guanine nucleotide-binding protein-coupled seven-transmembrane-domain receptor that controls the differentiation, growth, and function of the thyroid gland through stimulation of adenylyl cyclase and phospholipase C pathways. Thyroid stimulating hormone (TSH) is the main TSHR ligand, and unliganded receptor remains silent due to the interaction of its large extracellular domain with the extracellular loops of the serpentine. The TSHR gene is highly mutagenic and constitutively active mutations have been extensively described. Naturally occurring TSHR-activating mutations can affect any part of the receptor, but most activating mutations affect the serpentine region, and the majority of these are located in the third intracellular loop or transmembrane domain six. We describe several simple and relatively cheap methods used in our laboratory to study constitutive TSHR mutations that include (1) screening of TSHR gene mutations in paraffin-embedded thyroid tissue samples, (2) measurement of TSHR constitutive activity in vitro, (3) measurement of TSHR expression at cell surface by flow cytometry analysis, (4) TSH binding to TSHR, and (5) TSHR phosphorylation analysis. PMID- 21036243 TI - Assessment of constitutive activity of a G protein-coupled receptor, CPR2, in Cryptococcus neoformans by heterologous and homologous methods. AB - G protein-coupled receptors (GPCRs) comprise the largest superfamily of cell surface receptors and are primary targets for drug development. A variety of detection systems have been reported to study ligand-GPCR interactions. Using Saccharomyces cerevisiae to express foreign proteins has long been appreciated for its low cost, simplicity, and conserved cellular pathways. The yeast pheromone-responsive pathway has been utilized to assess a range of different GPCRs. We have identified a pheromone-like receptor, Cpr2, that is located outside of the MAT locus in the human fungal pathogen Cryptococcus neoformans. To characterize its function and potential ligands, we expressed CPR2 in a yeast heterologous expression system. To optimize for CPR2 expression in this system, pheromone receptor Ste3, regulator of G protein signaling (RGS) Sst2, and the cyclin-dependent kinase inhibitor Far1 were mutated. The lacZ gene was fused with the promoter of the FUS1 gene that is activated by the yeast pheromone signal and then introduced into yeast cells. Expression of CPR2 in this yeast heterologous expression system revealed that Cpr2 could activate the pheromone-responsive pathway without addition of potential ligands, suggesting it is a naturally occurring, constitutively active receptor. Mutation of a single amino acid, Leu(222), was sufficient to reverse the constitutive activity of Cpr2. In this chapter, we summarize methods used for assessing the constitutive activity of Cpr2 and its mutants, which could be beneficial for other GPCR studies. PMID- 21036244 TI - In vitro and in vivo assessment of mu opioid receptor constitutive activity. AB - Constitutive (basal) signaling has been described and characterized for numerous G protein coupled receptors (GPCRs). The relevance of this activity to disease, drug discovery and development, and to clinical pharmacotherapy is just beginning to emerge. Opioid receptors were the first GPCR systems for which there was definitive evidence presented for constitutive activity, with numerous studies now published on the regulation of this activity (e.g., structure/activity of the receptor as it relates to basal activity, pharmacology of ligands that act as agonists, inverse agonists and "neutral antagonists," etc.). This chapter summarizes some of the methods used to characterize constitutive activity at the mu opioid receptor (MOR) in preclinical in vitro and in vivo model systems. This includes cell-based systems that are useful for higher throughput screening of novel ligands and for studying variables that can impact basal tone in a system. In vivo assays are also described in which constitutive activity is increased in response to acute or chronic opioid agonist exposure and where withdrawal is precipitated with antagonists that may function as inverse agonists or "neutral" antagonists. The methods described have inherent advantages and disadvantages that need to be considered in any drug discovery/development program. A brief discussion of progress toward understanding the clinical implications of MOR constitutive activity in the management of opioid addiction and chronic pain is also included in this chapter. PMID- 21036245 TI - Constitutively active MU-opioid receptors. AB - The MU-opioid receptor is the G protein coupled receptor (GPCR) responsible for the analgesic, rewarding and unwanted effects of morphine and similar drugs. Constitutive activity of GPCRs is a phenomenon that likely reflects receptors spontaneous adopting conformations that can activate G proteins, and is likely to be common to most if not all GPCRs. Basal constitutive activity has been observed in some systems with MU-opioid receptors, and constitutive activity is expressed by mutant MU-opioid receptors with amino acid substitutions in regions known to be important for signaling. However, MU-opioid receptors are unique in that a putative constitutively active state of the receptor, the MU*-state, has been suggested to be induced by prolonged agonist treatment. The MU*-state is thought to contribute to processes underlying adaptation to and withdrawal from opioid treatment, and may have a ligand sensitivity distinct from basal constitutive activity of the MU-opioid receptor or that exhibited by MU-opioid receptor mutants. In this chapter, we outline methods for measuring constitutively active MU-opioid receptors, including some that take advantage of the fairly direct coupling of the receptor to ion channels. We also briefly summarize the pharmacology of the different constitutively active MU-opioid receptor states, and highlight the areas where we need to know more. We hope that a better understanding of constitutive activity at the MU-opioid receptor may provide information useful in developing ligands that access subsets of receptor conformations, offering the potential to fine-tune opioid pharmacotherapy. PMID- 21036246 TI - Protein kinase CK2 is a constitutively active enzyme that promotes cell survival: strategies to identify CK2 substrates and manipulate its activity in mammalian cells. AB - Protein kinase CK2 is a constitutively active protein serine/threonine kinase that is ubiquitously expressed and essential for the survival of eukaryotic cells. On the basis of its elevated expression in a number of human cancers and its ability to promote tumorigenesis in transgenic mice, CK2 has emerged as a promising candidate for molecular-targeted therapy. Accordingly, there has been considerable interest in identifying the cellular events that are regulated by CK2 and the cellular substrates of CK2 that are responsible for mediating its actions in cells. Large-scale phosphoproteomics studies are revealing extensive lists of candidate CK2 substrates on the basis that these proteins are phosphorylated at sites conforming to the consensus for phosphorylation by CK2. However, efforts to validate the vast majority of these candidates as bona fide physiological CK2 substrates have been hindered by the lack of systematic strategies to identify its direct substrates and manipulate its activity in intact cells. To overcome these limitations, we describe experimental procedures for isolating CK2 from bacteria and from mammalian cells to enable in vitro phosphorylation of candidate substrates. We also outline strategies for manipulating the levels and activity of CK2 in intact cells. Collectively, the methods that are presented in this chapter should enable the identification and characterization of CK2 substrates and CK2-regulated processes both in vitro and in living cells. PMID- 21036247 TI - Assessment of CK2 constitutive activity in cancer cells. AB - At variance with the great majority of protein kinases that become active only in response to specific stimuli and whose implication in tumors is caused by genetic alterations conferring to them unscheduled activity, the highly pleiotropic Ser/Thr-specific protein kinase CK2 is constitutively active even under normal conditions and no gain-of-function CK2 mutants are known. Nevertheless, CK2 level is abnormally high in cancer cells where it is believed to generate an environment favorable to the development of malignancy, through a mechanism denoted as "non-oncogene addiction." This makes CK2 not only an appealing target to counteract different kinds of tumors but also a valuable marker of cells predisposed to undergo neoplastic transformation owing to the presence in them of CK2 level exceeding a critical threshold. Such a prognostic exploitation of CK2 would imply the availability of methods suitable for the reliable, sensitive, and specific quantification of its activity in biological samples and in living cells. The aim of this chapter is to describe a number of procedures applicable to the quantitative determination of CK2 activity and to provide experimental details designed for rendering these assays as sensitive and selective as possible even in the presence of many other protein kinases. The procedures described roughly fall in three categories: (i) in vitro quantification of CK2 activity in crude biological samples and cell lysates; (ii) in-cell assay of endogenous CK2 activity based on the phosphorylation of reporter substrates; (iii) identification of CK2 targets in malignant and normal cells. PMID- 21036248 TI - Structural basis of the constitutive activity of protein kinase CK2. AB - Protein kinase CK2 (formerly referred to as casein kinase II) is an evolutionary conserved, ubiquitous protein kinase. In mammals, there are two paralog catalytic subunits, that is, CK2alpha (A1) and CK2alpha' (A2), and one CK2beta dimer, which together form the heterotetrameric holoenzyme. The presence of full functioning CK2alpha and CK2beta subunits are absolutely mandatory for embryonic development. Total knockouts are lethal. The CK2alpha' paralog seems to be an exception inasmuch as a total knockout only leads to sterility in male mice. The catalytic subunits are distantly related to the CMGC subfamily of protein kinases, such as the cyclin-dependent kinases (CDKs). There are some peculiarities associated with protein kinase CK2, which are not found with most of the other protein kinases: the enzyme is constitutively active, it can use ATP and GTP as phosphoryl donors, and it is found elevated in most tumors investigated and rapidly proliferating tissues. In this review, we explain (i) its constitutive activity at the intramolecular level, and (ii) come forward with a model how this protein kinase could be regulated in cells by a mechanism involving intermolecular interactions. PMID- 21036249 TI - Measuring the constitutive activation of c-Jun N-terminal kinase isoforms. AB - The c-Jun N-terminal kinases (JNK) are important regulators of cell growth, proliferation, and apoptosis. JNKs are typically activated by a sequence of events that include phosphorylation of its T-P-Y motif by an upstream kinase, followed by homodimerization and translocation to the nucleus. Constitutive activation of JNK has been found in a variety of cancers including non-small cell lung carcinomas, gliomas, and mantle cell lymphoma. In vitro studies show that constitutive activation of JNK induces a transformed phenotype in fibroblasts and enhances tumorigenicity in a variety of cell lines. Interestingly, a subset of JNK isoforms was recently found to autoactivate rendering the proteins constitutively active. These constitutively active JNK proteins were found to play a pivotal role in activating transcription factors that increase cellular growth and tumor formation in mice. In this chapter, we describe techniques and methods that have been successfully used to study the three components of JNK activation. Use of these techniques may lead to a better understanding of the components of JNK pathways and how JNK is activated in cancer cells. PMID- 21036251 TI - Constitutive activity of GPR40/FFA1 intrinsic or assay dependent? AB - Free fatty acid receptor 1 (FFA1; previously designated GPR40) is a potential therapeutic target for the treatment of diabetes and related metabolic disorders. Agonist-independent or constitutive activity is a feature associated with essentially all G protein-coupled receptors but the extent of this varies substantially between family members. In many situations, detection of such activity can be both assay- and context-dependent and may reflect the presence in the assay of an endogenous agonist. In studies on FFA1, experiments employing cell membrane preparations and the binding of [(35)S]guanosine 5'-O-[gamma thio]triphosphate to G proteins produce data consistent with a high-level constitutive activity of this receptor. Herein, we detail these assays and discuss approaches to determine if this is a measure of intrinsic receptor constitutive activity or if such results reflect the presence of an endogenous agonist. FFA1 is coupled predominantly to G proteins of the Galpha(q) subfamily. Activation of the receptor results, therefore, in the transient elevation of intracellular [Ca(2+)]. We also detail assays to measure such signals and consider whether they are appropriate to detect receptor constitutive activity. PMID- 21036250 TI - Measurement of constitutive MAPK and PI3K/AKT signaling activity in human cancer cell lines. AB - The growth and survival of cancer cells are often driven by constitutive activity in the mitogen-activated protein kinase (MAPK) and phospho-inositide 3-kinase (PI3K)/AKT signaling pathways. Activity in these signal transduction cascades is known to contribute to the uncontrolled growth and resistance to apoptosis that characterizes tumor progression. There is now a great deal of interest in therapeutically targeting these pathways in cancer using small molecule inhibitors. In this chapter, we describe methods to measure constitutive MAPK and AKT activity in melanoma cell lines, with a focus upon Western blotting, phospho flow cytometry, and immunofluorescence staining techniques. PMID- 21036253 TI - Measurement of orexin (hypocretin) and substance P effects on constitutively active inward rectifier K(+) channels in brain neurons. AB - Electrophysiological experiments in our laboratory have led to the discovery that the cholinergic neurons in the nucleus basalis in the rat forebrain possess constitutively active inward rectifier K(+) channels. Unlike cloned inward rectifier K(+) channels, these constitutively active inward rectifier K(+) channels were found to have unique properties, and thus were named "KirNB" (inward rectifier K(+) channels in the nucleus basalis). We found that slow excitatory transmitters, such as orexin (hypocretin) and substance P, suppress the KirNB channel, resulting in neuronal excitation. Furthermore, it was discovered that suppression of KirNB channels by these transmitters is through protein kinase C (PKC). This chapter describes detailed electrophysiological techniques for investigating the effects of orexin and substance P on constitutively active KirNB channels. For this purpose, we also present a method for culturing nucleus basalis cholinergic neurons in which KirNB channels exist. Then, we describe the procedures through which PKC has been determined to mediate inhibition of KirNB channels by orexin and substance P. There are probably many other transmitters which may produce effects on KirNB channels. This chapter will enable researchers to investigate the effects of such transmitters on KirNB channels and their roles in neuronal functions. PMID- 21036252 TI - Constitutive activity of TRP channels methods for measuring the activity and its outcome. AB - TRP channels participate in many cellular processes including cell death. These channels mediate these effects mainly by changing the cellular concentration of Ca(2+), a prominent cellular second messenger. Measuring the current-voltage relationship and state of activation of TRP channels is of utmost importance for evaluating their contribution to a cellular process within a spatial and temporal context. The study of TRP channels and characterization of their mode of activation will benefit and progress our understanding of each channel's role in specific cellular mechanisms. Many TRP channels exhibit constitutive activity, which is mostly observed in cell-based expression systems. This constitutive activity can lead, in many cases, to cellular degeneration, which can be readily observed morphologically and by biochemical assays. This chapter describes in brief different modes of TRP channel activity and their current-voltage relationships. The chapter outlines methods for visualizing this activity and methods to correlate between TRP channel activity and cell death, and it illustrates mechanisms that prevent cell death in spite of constitutive activity. Finally, it describes methods for qualitatively and quantitatively measuring the accompanied cellular degeneration. PMID- 21036254 TI - Characterization of G protein-coupled receptor kinase 4 and measuring its constitutive activity in vivo. AB - G protein-coupled receptor kinase 4 (GRK4) was originally identified in the brain and was initially thought to have a limited expression pattern and functionality; however, more recent studies have found that GRK4 is expressed in multiple tissues and cell types and that it contributes to cardiovascular disease. Additionally, human GRK4 exists as four splice variants and each variant can harbor at least three functionally relevant polymorphisms. The primary role of GRK4 is to phosphorylate G protein-coupled receptors (GPCR), which leads to desensitization of the G protein signaling mechanism while simultaneously recruiting beta-arrestins and initializing the internalization of the receptor. Interestingly, GRK4 has been shown to be constitutively active in some, but not all, cases. A constitutive active GRK could lead to increased beta-arrestin mediated signaling while inhibiting traditional/canonical GPCR-mediated signaling mechanisms. Therefore, it is important to determine if GRK4 is constitutively active in a system. Measuring agonist-mediated activity of GRK4 is relatively straightforward since it inhibits second messenger signaling; however, only a few studies have directly examined the constitutive activity of GRK4 which requires techniques without an agonist. Since GRK4 has significant biological effects, identifying the mechanism underlying GRK4's constitutive activity and ligand stimulated activity becomes increasingly important. Therefore, the methods provided here are designed to aid researchers in determining if GRK4 is expressed, and if so which GRK4 species is expressed, followed by procedures to identify if GRK4 is constitutively active in its model system. Last, procedures are explained for identifying if GRK4 is involved in its system in a nonconstitutive manner. The protocols described here are designed to be accessible to a wide range of scientists, which should allow for more laboratories to examine GRK4 constitutive activity as well as agonist-mediated activity. PMID- 21036255 TI - Voltage-clamp-based methods for the detection of constitutively active acetylcholine-gated I(K,ACh) channels in the diseased heart. AB - Vagal nerve stimulation can promote atrial fibrillation (AF) that requires activation of the acetylcholine (ACh)-gated potassium current I(K,ACh). In chronic AF (cAF), I(K,ACh) shows strong activity despite the absence of ACh or analogous pharmacological stimulation. This receptor-independent, constitutive I(K,ACh) activity is suggested to represent an atrial-selective anti-AF therapeutic target, but the underlying molecular mechanisms are unknown. This chapter provides an overview of the voltage-clamp techniques that can be used to study constitutive I(K,ACh) activity in atrial myocytes and summarizes briefly the current knowledge about the potential underlying mechanism(s) of constitutive I(K,ACh) activity in diseased heart. PMID- 21036256 TI - Assaying WAVE and WASH complex constitutive activities toward the Arp2/3 complex. AB - The Arp2/3 complex generates branched actin networks when activated by Nucleation Promoting Factors (NPFs). Among these, WAVE proteins are required for lamellipodia and ruffle formation, whereas WASH proteins are required for the fission of endosomes. Both WASH and WAVE NPFs are embedded into multiprotein complexes that provide additional functions and regulations. Understanding how these complexes regulate the activity of their NPF starts with the determination of the constitutive activity of the complex. In this chapter, we describe how to efficiently purify the WAVE and WASH complexes from human stable cell lines. We also describe how to verify that these complexes are not aggregated, a prerequisite for activity assays. We then provide a protocol to measure their activity toward the Arp2/3 complex using the well-established pyrene actin assay. Finally, we show how our fast purification protocol can be modified to detect the endogenous activity of the WAVE complex, providing an easy readout for the level of WAVE activation in cells. PMID- 21036257 TI - UK health, science, and overseas aid: not what they seem. PMID- 21036258 TI - The UK's continued shameful neglect of migrants' health. PMID- 21036259 TI - GAVI's challenges: funding and leadership. PMID- 21036260 TI - Increased resources for the Global Fund, but pledges fall short of expected demand. PMID- 21036261 TI - A counterfeit drug treaty: great idea, wrong implementation. PMID- 21036263 TI - David Weatherall: Lasker Award for pioneer in molecular medicine. PMID- 21036264 TI - Mixed messages on systemic therapies for diabetic retinopathy. PMID- 21036265 TI - Mixed messages on systemic therapies for diabetic retinopathy. PMID- 21036266 TI - Intensive treatment of hyperglycaemia: what are the objectives? PMID- 21036268 TI - Huntington's disease. PMID- 21036269 TI - Huntington's disease. PMID- 21036270 TI - Huntington's disease. PMID- 21036271 TI - New international consensus on health impact assessment. PMID- 21036273 TI - Regulating medical tourism. PMID- 21036274 TI - Why are drug trials in Alzheimer's disease failing? PMID- 21036275 TI - Does instant access to compiled information undermine clinical cognition? PMID- 21036276 TI - Puberty, stress, and sudden death. PMID- 21036277 TI - Medicare part B claims for chiropractic spinal manipulation, 1998 to 2004. AB - OBJECTIVE: The objective of this study was to examine the volume and rate of Medicare Part B claims for chiropractic spinal manipulation longitudinally from 1998 to 2004. METHODS: A descriptive retrospective analysis was performed on Medicare part B claims from 1998 to 2004 using the Medicare Part B Standard Analytical Variable Length File. Using a 5% random sample of Medicare part B claims, the total number of claims were determined for chiropractic spinal manipulation procedures, and the rate of chiropractic spinal manipulation procedures per 1000 beneficiaries. RESULTS: From 1998 through 2003, the number of chiropractic spinal manipulation claims increased by 38% (from 824,249 total claims in 1998 to 1,133,872 in 2003) followed by a 24% decline from 2003 to 2004. The rate of total chiropractic spinal manipulation claims rose 29% from 649 claims per 1000 beneficiaries per year in 1998 to a high of 839 claims per 1000 beneficiaries per year in 2003 and then declined by 25% to 632 claims per 1000 beneficiaries per year in 2004. CONCLUSION: Medicare Part B claims for chiropractic spinal manipulation increased significantly from 1998 to 2003 and then abruptly declined from 2003 to 2004. Estimates for 2004 are at variance with earlier published estimates. PMID- 21036278 TI - Identifying episodes of back pain using medical expenditures panel survey data: patient experience, use of services, and chronicity. AB - OBJECTIVE: To explore the correspondence between "Episodes-of-Pain" and "episodes of care" for individuals with back pain. METHODS: This study was a secondary analysis of Medical Expenditures Panel Survey (MEPS) 2-year longitudinal data. Individual use and utilization of back pain services were examined across ambulatory settings and providers, and linked to MEPS medical condition data to identify individuals with back pain who do not use or who delay or discontinue utilization of health services for back pain. "Episodes-of-Care" and Episodes-of Pain were approximated through round-by-round temporal mapping of MEPS back pain utilization events data and medical conditions data. RESULTS: Of 10,193 individuals with back pain, approximately one fifth did not actively seek care for their back pain. Utilization of services for back pain (Episodes-of-Care) does not always correspond with an individual's full experience of back pain (Episodes-of-Pain). Upwards of 20% of MEPS respondents who use services for some back pain episodes, reported additional episodes for which they do not use services. CONCLUSIONS: These findings suggest that other longitudinal studies based only on data that reflect service use, for example, claims data, may incorrectly infer the nature of back pain and back pain episodes. Many individuals report ongoing back pain that continues beyond their Episodes-of Care, and many individuals with persistent back pain may use prescription drugs, medical services, and other health services only intermittently. PMID- 21036279 TI - Manipulation or microdiskectomy for sciatica? A prospective randomized clinical study. AB - OBJECTIVE: The purpose of this study was to compare the clinical efficacy of spinal manipulation against microdiskectomy in patients with sciatica secondary to lumbar disk herniation (LDH). METHODS: One hundred twenty patients presenting through elective referral by primary care physicians to neurosurgical spine surgeons were consecutively screened for symptoms of unilateral lumbar radiculopathy secondary to LDH at L3-4, L4-5, or L5-S1. Forty consecutive consenting patients who met inclusion criteria (patients must have failed at least 3 months of nonoperative management including treatment with analgesics, lifestyle modification, physiotherapy, massage therapy, and/or acupuncture) were randomized to either surgical microdiskectomy or standardized chiropractic spinal manipulation. Crossover to the alternate treatment was allowed after 3 months. RESULTS: Significant improvement in both treatment groups compared to baseline scores over time was observed in all outcome measures. After 1 year, follow-up intent-to-treat analysis did not reveal a difference in outcome based on the original treatment received. However, 3 patients crossed over from surgery to spinal manipulation and failed to gain further improvement. Eight patients crossed from spinal manipulation to surgery and improved to the same degree as their primary surgical counterparts. CONCLUSIONS: Sixty percent of patients with sciatica who had failed other medical management benefited from spinal manipulation to the same degree as if they underwent surgical intervention. Of 40% left unsatisfied, subsequent surgical intervention confers excellent outcome. Patients with symptomatic LDH failing medical management should consider spinal manipulation followed by surgery if warranted. PMID- 21036280 TI - Performance and reliability of a variable rate, force/displacement application system. AB - OBJECTIVE: Spinal manipulation therapy (SMT), an intervention used to treat low back pain, has been demonstrated to affect the stiffness of the spine. To adequately quantify the effects of SMT on stiffness, a device capable of applying specific parameters of manipulation in addition to measuring force-displacement values has been developed previously. Previously developed indentation techniques that quantify stiffness have been modified for novel use in evaluating SMT parameters. The reliability of stiffness measurements performed by the newly adapted device was assessed in this study. METHODS: Seven springs of varying stiffness were each indented 10 times by a variable rate force/displacement (VRFD) device. Indentations were performed at a rate of 0.5 mm/s to a maximal displacement of 4 mm. The stiffness coefficients for a middle portion of the resulting force-displacement graph and the terminal instantaneous stiffness (stiffness at end displacement) were calculated. The intraclass correlation and confidence interval were calculated for these stiffness measurements to assess device reliability. RESULTS: Repeated spring stiffness measures yielded an intraclass correlation coefficient value of 1.0. The mean stiffness values had narrow 95% confidence intervals ranging from 0.01 N/mm to 0.06 N/mm and small coefficients of variation. CONCLUSION: This VRFD device provides highly reliable stiffness measurements in controlled conditions. Although in vivo reliability remains to be established, the results of this study support the use of the VRFD device in future trials investigating the impact of various SMT parameters on spinal stiffness. PMID- 21036281 TI - Functional anatomy of human scalene musculature: rotation of the cervical spine. AB - OBJECTIVES: Actions of the scalene muscles include flexion and lateral flexion of the cervical spine and elevation of the first and second ribs. The cervical rotational qualities of the scalene muscles remain unclear. Textbooks and recent studies report contradictory findings with respect to the cervical rotational properties of the scalene muscles. The present study was designed to take a mechanical approach to determining whether the scalene muscles produce rotation of the cervical spine. METHODS: The scalene muscles were isolated, removed, and replaced by a durable suture material. The suture material was attached at the origin and then passed through a hole on the corresponding rib near the central point of the insertion. The suture material was pulled down through the corresponding costal insertion hole to simulate contraction of each muscle. RESULTS: The simulated anterior, middle, and posterior scalene muscles, working independently and jointly, produced ipsilateral rotation of the cervical spine. The upper cervical spine rotated in the ipsilateral direction in response to the simulated muscle contraction. Findings were similar for the lower cervical spine with the exception of 2 specimens, which rotated contralaterally in response to the simulation. CONCLUSION: Experimental models of the scalene muscles are capable of producing ipsilateral rotation of the cervical spine. The findings of this study support the accepted main actions of the scalene muscles. The clinical applications for understanding the cervical rotational properties of the scalene muscles include the diagnosis, management, and treatment of cervical pain conditions as well as thoracic outlet syndrome. PMID- 21036282 TI - Impairment of postural stabilization systems in musicians with playing-related musculoskeletal disorders. AB - OBJECTIVE: Recent research demonstrates the importance of postural stabilization systems (PSS) in back pain. The purpose of this study was to examine the frequency of PSS disturbances in musicians experiencing playing-related musculoskeletal disorders (PRMDs). METHODS: Analysis for the presence of impaired PSS (lumbopelvic and scapular stabilizing system dysfunction, upper crossed syndrome) in 84 musicians. RESULTS: Analysis of clinical examination data revealed dysfunctions of the PSS to be present in 78 (93%) of these subjects. Eighty-five percent were found to have impairments of scapular, 71% impairments of lumbopelvic stabilization system, and 57% were found to have upper crossed syndrome. Subgroup analysis (upper strings, lower strings, wind and keyboard instruments) showed significantly more impairment of the lumbopelvic stabilization system for upper and lower strings (P = .008), whereas similar rates for disturbances of scapular stabilizers and upper crossed syndrome were seen across subgroups. Furthermore, significant sex differences with a higher frequency of scapular stabilizers (P = .014) and upper crossed syndrome (P < .001) in women were present. CONCLUSION: This study suggests that insufficiencies of the postural stabilization systems play an important role in the manifestation of musculoskeletal pain and PRMD in musicians. Although there are no prospective research data concerning PSS in musicians, the present authors' empirical observations and clinical experience support the notion that the clinical course and therapeutic outcomes of PRMD bear relationship to the function of the stabilization systems. We therefore argue for a greater emphasis on the examination and training of the postural systems in the integrated prevention, treatment, and rehabilitation of musicians. PMID- 21036283 TI - Validity of weekly recall ratings of average pain intensity in neck pain patients. AB - OBJECTIVE: Ratings of usual pain over a period of 1 week are commonly used to rate a patient's usual level of pain intensity. This study investigated the validity of weekly recall pain ratings and biasing effects of pain levels on these ratings. METHODS: Seventy-eight patients presenting to a chiropractic outpatient clinic with nonspecific neck pain completed a 7-day diary rating their pain 4 times each day on an 11-point numerical rating scale. From these 28 ratings, the patients' "actual average" pain was computed. On day 8, patients were asked to rate their current pain, as well as recall their pain "on average," at its "worst," and at its "least" over the previous week. RESULTS: Recall of average pain over the previous week was shown to be a valid measure using ratings of actual pain as the criterion standard (Pearson r = 0.95). The error between actual and recall readings was random and consistent across all levels of actual pain. Patients were also able to accurately recall their pain at its worst (r = 0.93) and at its least (r = 0.92) over the preceding week. In regression analyses, there were no appreciable biasing effects on the recall of average pain of either current pain at the time of recall, or of pain at its worst or at its least during the recall period. CONCLUSION: These results suggest that recall ratings of pain intensity may be valid for use in clinical research and practice on patients with nonspecific neck pain. PMID- 21036284 TI - Characteristics of chiropractors and their patients in Belgium. AB - OBJECTIVE: The purpose of this study is to describe the characteristics, practice characteristics, and opinions of chiropractors and the sociodemographic characteristics and the type of complaint of patients presenting to chiropractors in Belgium. METHODS: In 2008, all doctors of chiropractic in Belgium (N = 101) were asked to provide personal sociodemographic and practice-specific information via postal questionnaires. The participating practitioners presented written questionnaires to a maximum of 10 consecutive patients to collect sociodemographic and clinical data on the patients. Descriptive analyses were used. RESULTS: In total, 80 doctors of chiropractic (79.2%, n = 80/101) participated, providing information on 517 patients. Belgian doctors of chiropractic are predominantly male (75%), have a mean age of 44 (SD = 14) years, and have been in practice for 18 years on average. They typically treat neck and/or low back pain with or without radiating pain (85% of all complaints). Patients have a mean age of 43 (SD = 16.4) years, 54% are female, and most patients are employed (70%). Patients present with musculoskeletal complaints of moderate intensity, averaging 5 on a 0 to 10 numeric rating scale. Chiropractors spend, on average, 36 minutes on a new patient and 15 minutes on follow-up consultations. Diversified technique (93%) is the most often used technique, followed by mechanical-assisted (Activator) spinal manipulative therapy (41%). Ergonomic advice and instruction in exercise therapy are most often used in conjunction with spinal manipulative therapy. Most chiropractors would like to have the legal authority to request diagnostic imaging (87%). CONCLUSIONS: This is the first study describing doctors of chiropractic and their patients in Belgium. Chiropractors in Belgium primarily focus on the treatment of neuromusculoskeletal complaints in adults, with emphasis on the spine. Patients presenting to the chiropractor consult with musculoskeletal complaints of moderate intensity that moderately affect their activities of daily living. PMID- 21036285 TI - Lumbar disk protrusion rates of symptomatic patients using magnetic resonance imaging. AB - OBJECTIVE: The purpose of this study was to determine the rate of disk protrusions detected via magnetic resonance imaging (MRI) in patients symptomatic for spine pain, radiculopathy, or other spine-related pain. METHODS: A retrospective review of 1983 MRI scans was performed over a 2-year period on 1486 patients, each of whom was symptomatic for spine pain, radiculopathy, or other noncancer, spine-related pain. Of these patients, 761 were scanned in the recumbent position using low-field (0.3 T, Airis II, Hitachi, Twinsburg, Ohio) MRI, and 725 were scanned in an upright, sitting position using mid-field (0.6 T) open Upright MRI (Fonar, Melville, NY). In total, 986 serial scans were performed on patients in the recumbent position and 997 serial scans on patients in the weight-bearing position. RESULTS: One or more disk protrusions were identified in 73.3% of scans performed in the sitting position and in 50.1% of scans performed in the recumbent position. Most disk protrusions occurred at L5-S1 (52.3% and 29.8%), L4-L5 (42.6% and 26.7%), and L3-L4 (26.7% and 13.1%) in upright and recumbent positions, respectively. CONCLUSIONS: The disk protrusion rate in this group of patients ranged between 50.1% (recumbent) and 73.3% (weight-bearing). These rates are higher than rates reported in the medical literature for asymptomatic patients, a finding that supports the decision to further evaluate patients with persistent spine-related pain. PMID- 21036286 TI - Ultrasonography of the cervical muscles: a critical review of the literature. AB - OBJECTIVE: This article presents a review of the literature concerning size measurement of cervical muscles using real-time ultrasound imaging (RUSI) in patients with neck pain and in healthy populations. METHODS: A literature search from 1996 to December 2009 making use of Science Direct and PubMed databases was conducted. Medical Subject Headings and other terms were as follows: ultrasonography, cervical, muscle, neck, size, pain, validity, reliability, neck pain, and healthy subjects. We included studies using RUSI for assessing cervical paraspinal muscles both in healthy subjects and in patients with neck pain. We assessed muscles investigated and the reliability and validity of the method used. RESULTS: The literature search yielded 16 studies. Twelve (75%) studies assessed the posterior muscles, whereas in the remaining 4 (25%), the anterior muscles were studied. Three studies quantified the size of the muscles during contraction; 3 assessed the relationship between cross-sectional area, linear dimensions, and anthropometric variables; 1 evaluated the training-induced changes in muscle size; 1 assessed the differences in muscle shape and cross sectional area of cervical multifidus between patients with chronic neck pain and controls; 8 studies looked at the reliability of using RUSI in patients with neck pain or healthy subjects; and 3 studies evaluated the validity of RUSI compared with magnetic resonance imaging. CONCLUSIONS: This literature review has shown that there are not sufficient studies for assessing neck muscles with RUSI. It seems that using constant landmarks, knowledge of anatomy and function of target muscle, and a proper definition of muscle borders can help to take a clear image. Standardized position of the subject, correct placement of the transducer, and using multiple RUSI for statistical analyses may improve results. PMID- 21036287 TI - The varied implications of waiting room medicine. PMID- 21036288 TI - Images in emergency medicine. Man with back pain and rash. Perinephric abscess presenting as rash. PMID- 21036289 TI - Annals of emergency medicine journal club. Investigating rare events and a discussion on waiting room chest pain evaluations. PMID- 21036290 TI - Waiting room medicine: has it really come to this? PMID- 21036291 TI - The etomidate debate. PMID- 21036292 TI - Infectious disease/CDC update. Malaria acquired in Haiti-2010. Commentary. PMID- 21036294 TI - NIH Roundtable on Emergency Trauma Research. AB - STUDY OBJECTIVE: The National Institutes of Health (NIH) formed an NIH Task Force on Research in Emergency Medicine to enhance NIH support for emergency care research. The NIH Trauma Research Roundtable was convened on June 22 to 23, 2009. The objectives of the roundtable are to identify key research questions essential to advancing the scientific underpinnings of emergency trauma care and to discuss the barriers and best means to advance research by exploring the role of trauma research networks and collaboration between NIH and the emergency trauma care community. METHODS: Before the roundtable, the emergency care domains to be discussed were selected and experts in each of the fields were invited to participate in the roundtable. Domain experts were asked to identify research priorities and challenges and separate them into mechanistic, translational, and clinical categories. During and after the conference, the lists were circulated among the participants and revised to reach a consensus. RESULTS: Emergency trauma care research is characterized by focus on the timing, sequence, and time sensitivity of disease processes and treatment effects. Rapidly identifying the phenotype of patients on the time spectrum of acuity and severity after injury and the mechanistic reasons for heterogeneity in outcome are important challenges in emergency trauma research. Other research priorities include the need to elucidate the timing, sequence, and duration of causal molecular and cellular events involved in time-critical injuries, and the development of treatments capable of halting or reversing them; the need for novel experimental models of acute injury; the need to assess the effect of development and aging on the postinjury response; and the need to understand why there are regional differences in outcomes after injury. Important barriers to emergency care research include a limited number of trained investigators and experienced mentors, limited research infrastructure and support, and regulatory hurdles. CONCLUSION: The science of emergency trauma care may be advanced by facilitating the following: (1) development of an acute injury template for clinical research; (2) developing emergency trauma clinical research networks; (3) integrating emergency trauma research into Clinical and Translational Science Awards; (4) developing emergency care-specific initiatives within the existing structure of NIH institutes and centers; (5) involving acute trauma and emergency specialists in grant review and research advisory processes; (6) supporting learn-phase or small, clinical trials; (7) performing research to address ethical and regulatory issues; and (8) training emergency care investigators with research training programs. PMID- 21036296 TI - NIH and research in the emergency setting: progress, promise, and process. PMID- 21036293 TI - Summary of NIH Medical-Surgical Emergency Research Roundtable held on April 30 to May 1, 2009. AB - STUDY OBJECTIVE: In 2003, the Institute of Medicine Committee on the Future of Emergency Care in the United States Health System convened and identified a crisis in emergency care in the United States, including a need to enhance the research base for emergency care. As a result, the National Institutes of Health (NIH) formed an NIH Task Force on Research in Emergency Medicine to enhance NIH support for emergency care research. Members of the NIH Task Force and academic leaders in emergency care participated in 3 roundtable discussions to prioritize current opportunities for enhancing and conducting emergency care research. The objectives of these discussions were to identify key research questions essential to advancing the scientific underpinnings of emergency care and to discuss the barriers and best means to advance research by exploring the role of research networks and collaboration between the NIH and the emergency care community. METHODS: The Medical-Surgical Research Roundtable was convened on April 30 to May 1, 2009. Before the roundtable, the emergency care domains to be discussed were selected and experts in each of the fields were invited to participate in the roundtable. Domain experts were asked to identify research priorities and challenges and separate them into mechanistic, translational, and clinical categories. After the conference, the lists were circulated among the participants and revised to reach a consensus. RESULTS: Emergency care research is characterized by focus on the timing, sequence, and time sensitivity of disease processes and treatment effects. Rapidly identifying the phenotype and genotype of patients manifesting a specific disease process and the mechanistic reasons for heterogeneity in outcome are important challenges in emergency care research. Other research priorities include the need to elucidate the timing, sequence, and duration of causal molecular and cellular events involved in time critical illnesses and injuries, and the development of treatments capable of halting or reversing them; the need for novel animal models; and the need to understand why there are regional differences in outcome for the same disease processes. Important barriers to emergency care research include a limited number of trained investigators and experienced mentors, limited research infrastructure and support, and regulatory hurdles. The science of emergency care may be advanced by facilitating the following: (1) training emergency care investigators with research training programs; (2) developing emergency care clinical research networks; (3) integrating emergency care research into Clinical and Translational Science Awards; (4) developing emergency care-specific initiatives within the existing structure of NIH institutes and centers; (5) involving emergency specialists in grant review and research advisory processes; (6) supporting learn phase or small, clinical trials; and (7) performing research to address ethical and regulatory issues. CONCLUSION: Enhancing the research base supporting the care of medical and surgical emergencies will require progress in specific mechanistic, translational, and clinical domains; effective collaboration of academic investigators across traditional clinical and scientific boundaries; federal support of research in high-priority areas; and overcoming limitations in available infrastructure, research training, and access to patient populations. PMID- 21036297 TI - Butchers move the meat; doctors care for patients. PMID- 21036295 TI - NIH Roundtable on Opportunities to Advance Research on Neurologic and Psychiatric Emergencies. AB - STUDY OBJECTIVE: The Institute of Medicine Committee on the Future of Emergency Care in the United States Health System (2003) identified a need to enhance the research base for emergency care. As a result, a National Institutes of Health (NIH) Task Force on Research in Emergency Medicine was formed to enhance NIH support for emergency care research. Members of the NIH Task Force and academic leaders in emergency care participated in 3 Roundtable discussions to prioritize current opportunities for enhancing and conducting emergency care research. We identify key research questions essential to advancing the science of emergency care and discuss the barriers and strategies to advance research by exploring the collaboration between NIH and the emergency care community. METHODS: Experts from emergency medicine, neurology, psychiatry, and public health assembled to review critical areas in need of investigation, current gaps in knowledge, barriers, and opportunities. Neurologic emergencies included cerebral resuscitation, pain, stroke, syncope, traumatic brain injury, and pregnancy. Mental health topics included suicide, agitation and delirium, substances, posttraumatic stress, violence, and bereavement. RESULTS: Presentations and group discussion firmly established the need for translational research to bring basic science concepts into the clinical arena. A coordinated continuum of the health care system that ensures rapid identification and stabilization and extends through discharge is necessary to maximize overall patient outcomes. There is a paucity of well designed, focused research on diagnostic testing, clinical decisionmaking, and treatments in the emergency setting. Barriers include the limited number of experienced researchers in emergency medicine, limited dedicated research funding, and difficulties of conducting research in chaotic emergency environments stressed by crowding and limited resources. Several themes emerged during the course of the roundtable discussion, including the need for development of (1) a research infrastructure for the rapid identification, consent, and tracking of research subjects that incorporates innovative informatics technologies, essential for future research; (2) diagnostic strategies and tools necessary to understand key populations and the process of medical decisionmaking, including the investigation of the pathobiology of symptoms and symptom-oriented therapies; (3) collaborative research networks to provide unique opportunities to form partnerships, leverage patient cohorts and clinical and financial resources, and share data; (4) formal research training programs integral for creating new knowledge and advancing the science and practice of emergency medicine; and (5) recognition that emergency care is part of an integrated system from emergency medical services dispatch to discharge. The NIH Roundtable "Opportunities to Advance Research on Neurological and Psychiatric Emergencies" created a framework to guide future emergency medicine based research initiatives. CONCLUSION: Emergency departments provide the portal of access to the health care system for most patients with acute neurologic and psychiatric illness. Emergency physicians and colleagues are primed to investigate neurologic and psychiatric emergencies that will directly improve the delivery of care and patient outcomes. PMID- 21036298 TI - Phantom leg edema. PMID- 21036299 TI - Images in emergency medicine. Woman with leg swelling. Dissecting Baker's cyst. PMID- 21036300 TI - Endotracheal tube intracuff pressure during helicopter transport. PMID- 21036302 TI - Problems with PERC. PMID- 21036303 TI - PERC bleeding risk calculation and resultant test threshold may be inappropriate. PMID- 21036305 TI - Further consideration for noninvasive positive pressure ventilation in cardiogenic pulmonary edema. PMID- 21036306 TI - Processing dynamic facial affect in frequent cannabis-users: evidence of deficits in the speed of identifying emotional expressions. AB - BACKGROUND: While heavy cannabis-users seem to show various cognitive impairments, it remains unclear whether they also experience significant deficits in affective functioning. Evidence of such deficits may contribute to our understanding of the interpersonal difficulties in cannabis-users, and the link between cannabis-use and psychological disorders (Moore et al., 2007). METHOD: Emotion recognition performance of heavy cannabis-users and non-using controls was compared. A measure of emotion recognition was used in which participants identified facial expressions as they changed from neutral (open-mouth) to gradually more intense expressions of sadness, neutral, anger or happiness (open or closed mouth). Reaction times and accuracy were recorded as the facial expressions changed. Participants also completed measures of 'theory of mind,' depression and impulsivity. RESULTS: Cannabis-users were significantly slower than controls at identifying all three emotional expressions. There was no difference between groups in identifying facial expressions changing from open mouth neutral expressions to closed-mouth neutral expressions suggesting that differences in emotion recognition were not due to a general slowing of reaction times. Cannabis-users were also significantly more liberal in their response criterion for recognising sadness. CONCLUSION: Heavy cannabis-use may be associated with affect recognition deficits. In particular, a greater intensity of emotion expression was required before identification of positive and negative emotions. This was found using stimuli which simulated dynamic changes in emotion expression, and in turn, suggests that cannabis-users may experience generalised problems in decoding basic emotions during social interactions. The implications of these findings are discussed for vulnerability to psychological and interpersonal difficulties in cannabis-users. PMID- 21036307 TI - Peripartum cardiomyopathy may also present as "fulminant right ventricular myocarditis". PMID- 21036309 TI - Combined craniomaxillofacial and neurosurgical procedures. PMID- 21036310 TI - The coronal scalp flap: surgical technique. PMID- 21036312 TI - Endoscopic techniques for craniosynostosis. PMID- 21036311 TI - Craniosynostosis: diagnosis and surgical management. PMID- 21036313 TI - Craniofacial dysostosis syndromes: evaluation and staged reconstructive approach. PMID- 21036314 TI - Reconstruction of frontoethmoidal encephalocele defects. PMID- 21036315 TI - Reconstruction of skull defects. PMID- 21036316 TI - Craniofacial approach for anterior skull-base lesions. PMID- 21036317 TI - Evolution of endoscopic endonasal surgery of the skull base and paranasal sinuses. PMID- 21036318 TI - Frontobasilar fractures: contemporary management. PMID- 21036319 TI - Genes and obesity. Preface. PMID- 21036320 TI - Genetics and genomics of obesity: current status. PMID- 21036321 TI - Genes and pathways contributing to obesity: a systems biology view. AB - Systems biology is an expanding discipline that utilizes high-throughput data from multiple sources to develop models of biologic processes. This chapter reviews basic systems biology concepts and how they inform the traditional search for genes and pathways involved in disease pathogenesis. Systems approaches yield networks representing interactions and relationships among elements, with subnetworks or modules being functional groupings of these. For genetics of common disease-related traits such as obesity, integrative genetics is representative of a top-down systems biology approach, bringing together high throughput genotyping, global tissue mRNA expression data, and phenotypic data. Coexpression network analysis yields network models that allow identification of groups of coexpressed genes that can be related to particular traits. Combining this with genetics has shown that genetic variation at disease associated loci act though influencing such modules. Constraint-based reconstruction of metabolic networks represents a bottom-up systems biology approach that can be utilized to model the effects of genetic variation. The progressively increasing ability to generate high-throughput data of various types will promote continued application of systems approaches to better understand the processes by which genetic variation influences disease-related traits. PMID- 21036322 TI - Genetics of adipose tissue biology. AB - Adipose tissue morphology and release of free fatty acids, as well as peptide hormones, are believed to contribute to obesity and related metabolic disorders. These adipose tissue phenotypes are influenced by adiposity, but there is also a strong hereditary impact. Polymorphisms in numerous adipose-expressed genes have been evaluated for association with adipocyte and clinical phenotypes. In our opinion, some results are convincing. Thus ADRB2 and GPR74 genes are associated with adipocyte lipolysis, GPR74 also with BMI; PPARG and SREBP1, which promote adipogenesis and lipid storage, are associated with T2D and possible adiposity; ADIPOQ and ARL15 are associated with circulating levels of adiponectin, ARL15 also with coronary heart disease. We anticipate that the use of complementary approaches such as expression profiling and RNAi screening, and studies of additional levels of gene regulation, that is, miRNA and epigenetics, will be important to unravel the genetics of adipose tissue function. PMID- 21036323 TI - The genetics of brown adipose tissue. AB - Brown adipose tissue is highly differentiated and has evolved as a mechanism for heat production based upon uncoupling of mitochondrial oxidative phosphorylation. Additionally, large amounts of lipid can be stored in the cells to provide fuel necessary for heat production upon adrenergic stimulation from the central nervous system, and a highly developed vascular system evolved to rapidly deliver heat to vital organs. For unknown reasons, the development of brown adipocytes has two independent pathways: one originates from muscle progenitor cells in the fetus and leads to a fully functional cell at birth (interscapular-type brown fat), while the other transiently emerges in traditional white fat depots at weaning, regresses, and then can be induced in adult mice upon adrenergic stimulation. No genetic variants have been found for interscapular fat, but naturally occurring alleles at eight genetic loci in mice lead to over 100-fold variation for brown adipocytes in white fat upon adrenergic stimulation. The ability to activate this potential for energy expenditure is of great interest in obesity research. PMID- 21036324 TI - Obesity in single gene disorders. AB - In the 1980s, the heritability of obesity has been calculated to be around 0.80, implying a significant genetic origin and sparking a worldwide "gold-rush" for causative genes. Since the discovery of leptin and the body weight homeostasis pathway it regulates, we have come to a greater understanding of the factors that now control it. Nevertheless, we are still some way off reaching the goal of effectively managing the consequences of dysregulation: obesity, a disease related state that threatens the well-being of mankind. An unprecedented plethora of data has informed our understanding of obesogenic processes; this chapter examines the evidence, focusing on the substantial role of monogenic diseases. PMID- 21036325 TI - A translational view of the genetics of lipodystrophy and ectopic fat deposition. AB - A wide range of lipodystrophy syndromes exist, each with varying clinical presentations, and yet cumulatively they underscore the importance of adipocyte biology in human metabolism. Loss of the ability to retain excess lipids in "classical" adipose tissue stores can lead to the overdevelopment of ectopic fat stores, often creating severe perturbations of both glucose and lipid homeostasis. Linkage analysis and candidate sequencing efforts have successfully identified responsible mutations for multiple forms of lipodystrophy. Recently, the reduction in the cost of DNA sequencing has resulted in discovery of many novel mutations within both known and novel loci. In this review, we present the steps involved in clinical characterization of a suspected lipodystrophy case, an overview of the clinical manifestations, molecular findings, and pathogenic basis of different forms of lipodystrophy, a discussion of therapeutic options for lipodystrophy patients, and an examination of genetic advances that will be used to identify additional pathogenic mechanisms. PMID- 21036326 TI - Cutting the fat: the genetic dissection of body weight. AB - Variation in body weight and composition, as well as adipose tissue function, is regulated by environmental and genetic factors, combined with a variety of interactions, including environment-by-environment, gene-by-gene, and gene-by environment interactions. Although the recent increase in obesity can in large part be attributed to the increased availability of low-cost but energy-dense foods and an increasingly sedentary lifestyle throughout most of the developed world, the impact of these factors is more pronounced in individuals who are genetically susceptible to these environmental insults. Hence, it is likely to be the response of an individual's genetic background to a given environment that determines susceptibility to obesity. Candidate gene studies, genome-wide linkage studies, and more recently genome-wide association studies (GWASs) have been used to decipher the effect of genetics on obesity. Heritability estimates suggest that 40-70% of the variation in obesity-related phenotypes is attributable to underlying genetic variation. To date, the findings from human cohort studies (both family and case/control studies) summarized in this chapter suggest that there are likely numerous genes impacting the expression of obesity-related phenotypes, with many of these genes seeming to have modest effects. The establishment of many population-based studies that have collected genome-wide data on genetic variation has recently led to the formation of multiple consortia facilitating powerful meta-analyses in order to identify additional genetic variation influencing obesity-related traits through GWAS, as well as to replicate and further characterize previously identified genetic variants and their gene regions. These consortia may have the power to elucidate how genetic and environmental factors act and interact to produce variation in obesity related phenotypes. PMID- 21036328 TI - Genetic findings in anorexia and bulimia nervosa. AB - Anorexia nervosa (AN) and bulimia nervosa (BN) are complex disorders associated with disordered eating behavior. Heritability estimates derived from twin and family studies are high, so that substantial genetic influences on the etiology can be assumed for both. As the monoaminergic neurotransmitter systems are involved in eating disorders (EDs), candidate gene studies have centered on related genes; additionally, genes relevant for body weight regulation have been considered as candidates. Unfortunately, this approach has yielded very few positive results; confirmed associations or findings substantiated in meta analyses are scant. None of these associations can be considered unequivocally validated. Systematic genome-wide approaches have been performed to identify genes with no a priori evidence for their relevance in EDs. Family-based scans revealed linkage peaks in single chromosomal regions for AN and BN. Analyses of candidate genes in one of these regions led to the identification of genetic variants associated with AN. Currently, an international consortium is conducting a genome-wide association study for AN, which will hopefully lead to the identification of the first genome-wide significant markers. PMID- 21036327 TI - Genetics of taste and smell: poisons and pleasures. AB - Eating is dangerous. While food contains nutrients and calories that animals need to produce heat and energy, it may also contain harmful parasites, bacteria, or chemicals. To guide food selection, the senses of taste and smell have evolved to alert us to the bitter taste of poisons and the sour taste and off-putting smell of spoiled foods. These sensory systems help people and animals to eat defensively, and they provide the brake that helps them avoid ingesting foods that are harmful. But choices about which foods to eat are motivated by more than avoiding the bad; they are also motivated by seeking the good, such as fat and sugar. However, just as not everyone is equally capable of sensing toxins in food, not everyone is equally enthusiastic about consuming high-fat, high-sugar foods. Genetic studies in humans and experimental animals strongly suggest that the liking of sugar and fat is influenced by genotype; likewise, the abilities to detect bitterness and the malodors of rotting food are highly variable among individuals. Understanding the exact genes and genetic differences that affect food intake may provide important clues in obesity treatment by allowing caregivers to tailor dietary recommendations to the chemosensory landscape of each person. PMID- 21036330 TI - Epigenetics and obesity. AB - The etiology of obesity is multifactorial, involving complex interactions among the genetic makeup, neuroendocrine status, fetal programming, and different unhealthy environmental factors, such as sedentarism or inadequate dietary habits. Among the different mechanisms causing obesity, epigenetics, defined as the study of heritable changes in gene expression that occur without a change in the DNA sequence, has emerged as a very important determinant. Experimental evidence concerning dietary factors influencing obesity development through epigenetic mechanisms has been described. Thus, identification of those individuals who present with changes in DNA methylation profiles, certain histone modifications, or other epigenetically related processes could help to predict their susceptibility to gain or lose weight. Indeed, research concerning epigenetic mechanisms affecting weight homeostasis may play a role in the prevention of excessive fat deposition, the prediction of the most appropriate weight reduction plan, and the implementation of newer therapeutic approaches. PMID- 21036331 TI - Genetics of the metabolic complications of obesity. PMID- 21036332 TI - Obesity: from animal models to human genetics to practical applications. AB - Although many animal models are used in genetic studies, the mouse is most common. Analysis of single-gene mutations, linkage analysis in crossbred strains, and gene targeting are the primary techniques used to associate obesity phenotypes with specific genes or alleles. The orthologous human gene can then be tested, either in linkage studies in families or in genome-wide association studies (GWAS), for effect on the phenotype. Frequent lack of concordance between mouse and human obesity genes may be due to the difference in phenotypes measured in humans (body mass index) versus mouse (fat mass or % body fat), lack of intermediate phenotypes, and the fact that identified genes account for only a small percentage of the heritability of common obesity, suggesting that many genes remain unknown. New technology allows analysis of individual genomes at a reasonable cost, making large-scale obesity genome projects in humans feasible. Such projects could identify common allelic variants that contribute to obesity and to variable individual response to obesity therapy. Currently, family history may be more predictive than genetics for risk of obesity, but individual testing could ultimately guide therapy and, in the aggregate, guide public health policy. The primary limitation to development of genotype-based diets is that successful randomized diet trials of widely ranging macronutrient content, adequately powered for finding rare Mendelian mutations, have not been performed. PMID- 21036329 TI - Driven to be inactive? The genetics of physical activity. AB - The health implications of physical inactivity, including its integral role in promoting obesity, are well known and have been well documented. Physical activity is a multifactorial behavior with various factors playing a role in determining individual physical activity levels. Research using both human and animal models in the past several years has clearly indicated that genetics is associated with physical activity. Furthermore, researchers have identified several significant and suggestive genomic quantitative trait loci associated with physical activity. To date, the identities of the causal genes underlying physical activity regulation are unclear, with few strong candidate genes. The current research provides a foundation from which future confirmatory research can be launched as well as determination of the mechanisms through which the genetic factors act. The application of this knowledge could significantly augment the information available for physical activity behavior change interventions resulting in more efficient programs for those predisposed to be inactive. PMID- 21036333 TI - Endophytic fungal diversity in Theobroma cacao (cacao) and T. grandiflorum (cupuacu) trees and their potential for growth promotion and biocontrol of black pod disease. AB - The endophytic niches of plants are a rich source of microbes that can directly and indirectly promote plant protection, growth and development. The diversity of culturable endophytic fungi from stems and branches of Theobroma cacao (cacao) and Theobroma grandiflorum (cupuacu) trees growing in the Amazon region of Brazil was assessed. The collection of fungal endophytic isolates obtained was applied in field experiments to evaluate their potential as biocontrol agents against Phytophthora palmivora, the causal agent of the black-pod rot disease of cacao, one of the most important pathogens in cocoa-producing regions worldwide. The isolated endophytic fungi from 60 traditional, farmer-planted, healthy cacao and 10 cupuacu plants were cultured in PDA under conditions inducing sporulation. Isolates were classified based upon the morphological characteristics of their cultures and reproductive structures. Spore suspensions from a total of 103 isolates that could be classified at least up to genus level were tested against P. palmivora in pods attached to cacao trees in the field. Results indicated that ~70% of isolates showed biocontrol effects to a certain extent, suggesting that culturable endophytic fungal biodiversity in this system is of a mostly mutualistic type of interaction with the host. Eight isolates from genera Trichoderma (reference isolate), Pestalotiopsis, Curvularia, Tolypocladium and Fusarium showed the highest level of activity against the pathogen, and were further characterized. All demonstrated their endophytic nature by colonizing axenic cacao plantlets, and confirmed their biocontrol activity on attached pods trials by showing significant decrease in disease severity in relation to the positive control. None, however, showed detectable growth-promotion effects. Aspects related to endophytic biodiversity and host-pathogen-endophyte interactions in the environment of this study were discussed on the context of developing sustainable strategies for biological control of black-pod rot of cacao. PMID- 21036334 TI - The entomopathogen Metarhizium anisopliae can modulate the secretion of lipolytic enzymes in response to different substrates including components of arthropod cuticle. AB - The filamentous fungus Metarhizium anisopliae is a well-characterized, arthropod pathogen used in the biological control of arthropod pests. Studies on the regulation of enzymes related to host infection such as proteases and chitinases have been reported but little is known about regulation of lipolytic enzymes in this fungus. Here we present the effects of different carbon sources such as components of the arthropod cuticle on the secretion of lipolytic enzymes by M. anisopliae. Differences in the induction of lipolytic activity were observed between the several carbon sources tested. Higher activities of lipase or lipase/esterase were found in culture media containing the arthropod integument components chitin and cholesteryl stearate. Several bands of lipolytic activity were also detected in zymograms, thus suggesting an important set of lipolytic enzymes secreted by the fungus. These results show that the fungus can modulate the secretion of lipolytic activity in response to host integument components, thus reinforcing the potential role of these enzymes during M. anisopliae infection. PMID- 21036335 TI - Polymorphic change of appressoria by the tomato powdery mildew Oidium neolycopersici on host tomato leaves reflects multiple unsuccessful penetration attempts. AB - The appressorial shapes of the powdery mildews are an important clue to the taxonomy of the powdery mildew fungi, but the conidia of the tomato powdery mildew Oidium neolycopersici KTP-01 develop non-lobed, nipple-shaped, and moderately lobed or multilobed appressoria on the same leaves. To remove this ambiguity, we performed consecutive observations of sequential appressorial development of KTP-01 conidia with a high-fidelity digital microscope. Highly germinative conidia of KTP-01, collected from conidial pseudochains formed on the tomato leaves, were inoculated into host tomato and nonhost barley leaves or an artificial hydrophobic membrane (Parafilm). Events from germination initiation to appressorium formation were synchronous in all conidia on all materials used for inoculation, but post-appressorial behaviors varied among the materials. Appressoria on the membrane-stuck glass slide formed several projections at different portions of the appressoria to repeat unsuccessful penetration attempts. Similar unsuccessful penetration behavior by KTP-01 conidia was observed in the inoculations into leaves of barley plants, wild tomato species Lycopersicon peruvianum LA2172 (carrying the Ol-4 gene for powdery mildew resistance), and a susceptible host tomato (Lycopersicon esculentum) that had been inoculated with the barley powdery mildew (Blumeria graminis f. sp. hordei, race 1) conidia. On the barley leaves, all penetrations of KTP-01 were impeded by the papillae formed beneath the sites of the appressorial projections. On both the wild tomato and the race 1-inoculated cultivated tomato plants, KTP-01 conidia were prevented from forming functional haustoria by hypersensitive epidermal cell death; this hypersensitive reaction involved the Ol-4 gene in the wild tomato plants or the 'induced resistance' acquired by the nonpathogenic conidia previously inoculated into the cultivated tomato plants. All these KTP-01 conidia produced several projections on the appressoria during the repeated unsuccessful penetration attempts and eventually exhibited multilobed appressoria. On the host tomato leaves inoculated singly with KTP-01 conidia, fewer than 20% of the conidia located appressoria on the central part of target epidermal cells and succeeded in forming functional haustoria at the first penetration attempt without forming an appressorial projection. These conidia exhibited non-lobed appressoria. The remaining conidia, however, whose appressoria were located on/near the border of the target epidermal cells, were more likely to fail to penetrate at the first penetration, and then to develop additional projections for subsequent penetrations. Most conidia succeeded in forming functional haustoria at the second to fourth penetration attempts, but a few conidia failed to produce haustoria at all attempted penetrations. Eventually, the conidia that succeeded at the second penetration possessed a single appressorial projection (exhibiting the nipple-shaped appressoria), whereas the remaining conidia exhibited moderately lobed appressoria with two to four appressorial projections and multilobed appressoria, with more projections. Thus, the present study revealed that the basic shape of appressoria of KTP-01 was the non-lobed type, and that polymorphic changes of the appressoria occurred as a result of successive production of projections during repeated unsuccessful penetration attempts. PMID- 21036336 TI - Effect of long-term preservation of basidiomycetes on perlite in liquid nitrogen on their growth, morphological, enzymatic and genetic characteristics. AB - The macro- and micro-morphological features, mycelial extension rate, enzymatic activities and possible genetic changes were studied in 30 selected strains of basidiomycetes after 10-year cryopreservation on perlite in liquid nitrogen (LN). Comparisons with the same strains preserved by serial transfers on nutrient media at 4 degrees C were also conducted. Production of ligninolytic enzymes and hydrogen peroxide was studied by quantitative spectrophotometric methods, whereas semiquantitative API ZYM testing was used to compare the levels of a wide range of hydrolytic enzymes. Our results show that cryopreservation in LN did not cause morphological changes in any isolate. The vitality of all fungi was successfully preserved and none of the physiological features were lost, even though the extension rate and enzyme activity were slightly affected. Moreover, sequence analysis of eight strains did not detect any changes in their genetic features after cryopreservation. These findings suggest that the perlite-based freezing protocol is suitable for long-term preservation of large numbers of basidiomycetes. PMID- 21036337 TI - New evidence for nitrogen fixation within the Italian white truffle Tuber magnatum. AB - Diversity of nitrogen-fixing bacteria and the nitrogen-fixation activity was investigated in Tuber magnatum, the most well-known prized species of Italian white truffle. Degenerate PCR primers were applied to amplify the nitrogenase gene nifH from T. magnatum ascomata at different stages of maturation. Putative amino acid sequences revealed mainly the presence of Alphaproteobacteria belonging to Bradyrhizobium spp. and expression of nifH genes from Bradyrhizobia was detected. The nitrogenase activity evaluated by acetylene reduction assay was 0.5-7.5MUmolC(2)H(4)h(-1)g(-1), comparable with early nodules of legumes associated with specific nitrogen-fixing bacteria. This is the first demonstration of nitrogenase expression gene and activity within truffle. PMID- 21036338 TI - Solving the aerodynamics of fungal flight: how air viscosity slows spore motion. AB - Viscous drag causes the rapid deceleration of fungal spores after high-speed launches and limits discharge distance. Stokes' law posits a linear relationship between drag force and velocity. It provides an excellent fit to experimental measurements of the terminal velocity of free-falling spores and other instances of low Reynolds number motion (Re<1). More complex, non-linear drag models have been devised for movements characterized by higher Re, but their effectiveness for modeling the launch of fast-moving fungal spores has not been tested. In this paper, we use data on spore discharge processes obtained from ultra-high-speed video recordings to evaluate the effects of air viscosity predicted by Stokes' law and a commonly used non-linear drag model. We find that discharge distances predicted from launch speeds by Stokes' model provide a much better match to measured distances than estimates from the more complex drag model. Stokes' model works better over a wide range projectile sizes, launch speeds, and discharge distances, from microscopic mushroom ballistospores discharged at <1 m s(-1) over a distance of <0.1mm (Re<1.0), to macroscopic sporangia of Pilobolus that are launched at >10 m s(-1) and travel as far as 2.5m (Re>100). PMID- 21036339 TI - Microsatellite stability in the plant pathogen Botrytis cinerea after exposure to different selective pressures. AB - The stability of microsatellite markers was investigated in the spore-producing fungus Botrytis cinerea exposed to four growth conditions. This knowledge is essential in order to differentiate mutations from genetic exchanges or recombination in population genetics studies. It is also important when using strains from collections that need to be regularly propagated on medium. Successive spore generations of four isolates of the fungus were realised in plates on different agar media: a nutrient-rich medium, a nutrient-poor medium, a medium supplemented with the antibiotic pyrrolnitrin and a medium supplemented with the fungicide iprodione. The stability of nine microsatellite markers was studied by comparing the molecular pattern obtained between the wild type parent strains and the final generations obtained. The results showed that, despite the phenotypic changes observed in some generations, no changes were observed in the allele size at nine microsatellite loci whatever the selective pressure endured by the fungus. This is the first study that reveals long-term stability of microsatellite markers of a spore-producing fungus exposed to different stresses. PMID- 21036340 TI - A novel putative partitivirus of the saprotrophic fungus Heterobasidion ecrustosum infects pathogenic species of the Heterobasidion annosum complex. AB - We characterized the bisegmented genome of a putative double-stranded (ds) RNA virus from a Chinese isolate of the fungus Heterobasidion ecrustosum, a member of the Heterobasidion insulare species complex. The larger genomic segment of 1885bp encoded a putative RNA dependent RNA polymerase (RdRp, 585aa), and the smaller one for a putative coat protein of 521aa (1826bp). Phylogenetic analyses suggest that this novel virus species, named as 'Heterobasidion RNA virus 3 from H. ecrustosum, strain 1' (HetRV3-ec1), can be assigned to the family Partitiviridae, being most similar to the Helicobasidium mompa dsRNA mycovirus with RdRp amino acid similarity of 54%. The similarity to known viruses of other Heterobasidion species was notably low (25-39%). The virus could be experimentally transmitted to members of the Heterobasidion annosum complex: the European Heterobasidion abietinum and North American Heterobasidion occidentale, and the original host strain could be cured from the virus by thermal treatment. Microscopical observations showed that hyphae of H. ecrustosum anastomosed occasionally with H. abietinum and H. occidentale, and suggested a possible route for horizontal transmission between these sexually incompatible species. The virus infection seemed to cause variable effects on the growth rate of its fungal hosts, but the results were strongly dependent on fungal strain, growth medium and incubation temperature. PMID- 21036341 TI - Multigene phylogenetic and population differentiation data confirm the existence of a cryptic species within Chrysoporthe cubensis. AB - Chrysoporthe cubensis is one of the most important pathogens of Eucalyptus. Based on phylogenetic evidence and geographic origin, isolates of this fungus are known to reside in distinct 'South America' and 'Southeast Asia' clades. In this study, reproductive isolation amongst these isolates of C. cubensis was tested using gene flow statistics for 12 polymorphic loci, and to support these data, phylogenetic affiliations based on gene trees and a multigene phylogeny were used. Gene flow statistics between populations, and relative to the closely related Chrysoporthe austroafricana, were low and not significantly different (P<0.05). Additionally, phylogenetic analyses of DNA sequence data for four gene regions convincingly distinguished the two subclades of C. cubensis. Isolates in the Southeast Asian subclade are described in the new species, Chrysoporthe deuterocubensis. Chrysoporthe cubensis and C. deuterocubensis represent closely related fungi that are thought to be native to South America and Southeast Asia, respectively. A technique is presented that allows for rapid differentiation between these species and that will aid in quarantine procedures to limit their spread to new environments. PMID- 21036342 TI - Mating type idiomorphs from a French population of the wheat pathogen Mycosphaerella graminicola: widespread equal distribution and low but distinct levels of molecular polymorphism. AB - Septoria tritici blotch caused by the heterothallic ascomycete Mycosphaerella graminicola is currently the most frequent and the most economically damaging disease on wheat worldwide. Five hundred and ten strains of this fungus were sampled from 16 geographical locations representing the major wheat producing areas in France. Multiplex PCR amplification, PCR-RFLP-SSCP screening and sequencing of parts of mating type encoding sequences were performed in order to assess the distribution and molecular polymorphism of the mating type idiomorphs. The two idiomorphs were scored at similar frequencies within all sampled locations. Both mating types were also identified at the leaf spatial scale, on 42% of leaves from which two or three strains were isolated. No correlation was found between distribution of mating types and either host cultivars from which the sampling was carried out or in vitro colony phenotypes observed during the culture of strains on potato dextrose agar (PDA) medium. PCR-RFLP-SSCP assay highlighted only one MAT1-1 strain exhibiting a profile distinct from all other MAT1-1 strains, whereas ten MAT1-2 strains (among which two and four with same profiles, respectively) showed profiles differing from the other MAT1-2 strains. Sequencing revealed that all polymorphisms corresponded to single nucleotide variations and all strains displaying the same single strand conformation polymorphism (SSCP) profiles showed identical nucleotide sequences, thereby confirming the high sensitivity of SSCP. Only two out of the disclosed nucleotide variations were nonsynonymous. This study strongly suggests a large potential for sexual reproduction in the French population of M. graminicola and reports a high conservation of mating type sequences in the fungus at both nucleotide and population levels, with a great difference in molecular variability between the two idiomorphs. PMID- 21036343 TI - The foliar endophytic fungal community composition in Cirsium arvense is affected by mycorrhizal colonization and soil nutrient content. AB - Foliar fungal endophytes are ubiquitous, but understudied symbionts of most plant species; relatively little is known about the factors affecting their occurrence, diversity and abundance. We tested the effects of soil nutrient content and arbuscular mycorrhizal (AM) colonization on the occurrence of foliar endophytic fungi in Cirsium arvense in two field studies. In the first study, we assessed relationships between soil moisture, organic matter, carbon and nitrogen content and plant water, nitrogen and carbon content and AM colonization and the occurrence of foliar endophytic fungal species. In the second study, we manipulated soil nutrient content and AM colonization of potted seedlings and identified differences in endophytic fungal species composition of the leaves and stems. The results reveal that endophytes can occur either more or less frequently, depending on soil nutrient and plant water content and AM colonization. We propose that these patterns were the result of differences in fungal growth responses to nutrient availability in the leaves, which can be affected by resources obtained from the soil or symbiotic fungi in the roots. PMID- 21036344 TI - Differential regulation of laccase gene expression in Coriolopsis rigida LPSC No. 232. AB - Two laccase isoenzyme genes (lcc2 and lcc3) from the white-rot fungus Coriolopsis rigida were cloned, and together with the previously described lcc1, their transcript levels were analysed by Quantitative RT-PCR in order to study their expression patterns under a range of putative inducers (Cu(2+), Mn(2+), Fe(3+), 2,6-dimethoxy-1,4-benzoquinone, H(2)O(2,) caffeine, amphotericin B and syringic acid). The highest induction was observed for lcc1 in presence of copper, and thus, a kinetic study was performed to analyze its effect on temporary lcc1 gene expression. Our results showed that upregulation due to copper was linked to growth stage, being highest during the trophophase and decreasing during the idiophase. Amphotericin B increased levels of transcripts of lcc1 and lcc2, syringic acid upregulated lcc1 and lcc3 and 2,6-dimethoxy-1,4-benzoquinone induced lcc2 and lcc3. Possible reasons for why laccase genes from C. rigida are differentially regulated at the transcriptional level are discussed. PMID- 21036345 TI - Liming in a beech forest results in more mineral elements stored in the mantle of Lactarius subdulcis ectomycorrhizas. AB - Liming is a forest practice used to counteract forest decline induced by soil acidification. It consists of direct Ca and Mg input in forest soil and restores tree mineral nutrition, but also causes drastic changes in nutrient availability in soil. Ectomycorrhizal (ECM) fungi significantly contribute in nutrient uptake by trees, and can recover them through organic acid secretion or through enzymatic degradation of organic matter. The symbiotic fungi use their extraradical mycelium for nutrient uptake, and then store them into the ECM mantle. In this study we measured how liming influences element contents in the mantle of Lactarius subdulcis ECMs, an abundant and particularly active in oxalate and laccase secretion in beech stands. For this purpose we used SEM observation coupled with energy- (EDX) and wavelength-dispersive-X-ray microanalyses (WDX). Results showed that ECM mantles of this species presented significantly higher Ca, Mg, Mn, K, Si, Al and Fe contents in limed plots. The nutrient amounts of L. subdulcis ECMs were significantly different between individuals for all the elements, showing a differential storage ability between individuals. The storage role of the ECM mantle can be interpreted in two different ways: i) a detoxification role for Al or heavy metals and ii) an increased potential nutrient resource by the fungus, which can benefit the tree. PMID- 21036346 TI - Postural and focal inhibition of voluntary movements prepared under various temporal constraints. AB - Large disturbances arising from the moving segments (focal movement) are commonly counteracted by anticipatory postural adjustments (APAs). The aim of this study was to investigate how APAs - focal movement coordination changes under temporal constraint. Ten subjects were instructed to perform an arm raising movement in the reactive (simple reaction time) and predictive (anticipation-coincidence) tasks. A stop paradigm was applied to reveal the coordination. On some unexpected trials, a stop signal indicated to inhibit the movement; it occurred randomly at different delays (SOA) relative to the go signal in the reactive task, and at different delays prior to the focal response initiation in the predictive task. Focal movement was measured using contact switch, accelerometer and EMG from the anterior deltoid. APAs were quantified using centre of pressure displacement and EMG from three postural muscles. The inhibition rates as a function of the SOA produce psychometric functions where the bi-serial points allow the moment of the motor "command release" to be estimated. Repeated measures ANOVAs showed that APAs and focal movement were closely timed in the reactive task but distinct in a predictive task. Data were discussed according to two different models of coordination: (1) hierarchical model where APAs and focal movement are the results of a single motor command; (2) parallel model implying two independent motor commands. The data clearly favor the parallel model when the temporal constraint is low. The stop paradigm appears as a promising technique to explore APAs - focal movement coordination. PMID- 21036347 TI - A usability evaluation toolkit for In-Vehicle Information Systems (IVISs). AB - Usability must be defined specifically for the context of use of the particular system under investigation. This specific context of use should also be used to guide the definition of specific usability criteria and the selection of appropriate evaluation methods. There are four principles which can guide the selection of evaluation methods, relating to the information required in the evaluation, the stage at which to apply methods, the resources required and the people involved in the evaluation. This paper presents a framework for the evaluation of usability in the context of In-Vehicle Information Systems (IVISs). This framework guides designers through defining usability criteria for an evaluation, selecting appropriate evaluation methods and applying those methods. These stages form an iterative process of design-evaluation-redesign with the overall aim of improving the usability of IVISs and enhancing the driving experience, without compromising the safety of the driver. PMID- 21036348 TI - Photoinactivation of F. nucleatum and P. gingivalis using the ruthenium-based RD3 sensitizer and a conventional halogen lamp. AB - OBJECTIVE: The photodynamic therapy (PDT) is an alternative method to suppress oral pathogens by the activation of a photosensitizer with laser light. The aim of this study was to investigate the phototoxic effect of three ruthenium-based photosensitizers on Fusobacterium nucleatum and Porphyromonas gingivalis. METHODS: In this in vitro study F. nucleatum and P. gingivalis were incubated with three photosensitizers: (i) a hydrophobic tris-(4,7-diphenyl-1,10 phenanthroline)-ruthenium(II)-dication (RD3), (ii) a hydrophilic tris-[(1,10 phenanthroline-4,7-diyl)-bis-(benzenesulfonato)]-ruthenate tetra-anion (RSD3) and (iii) a lower hydrophilic tris-(2,2'-bipyridine)-ruthenium(II) dication (RBY). The subsequent irradiation was done with blue-band halogen light (450-485nm) for 20s using a conventional polymerizer. Control samples consisted of bacterial cell suspension irradiated and non-irradiated in the absence of photosensitizer or incubated with the photosensitizer without irradiation. Bacterial inactivation was determined by the numbers of colony-forming units (cfu/ml) after anaerobic cultivation. RESULTS: The RD3 photosensitizer reduced the viability of F. nucleatum by 4-log10 and of P. gingivalis completely after irradiation for 20s. The viability loss correlated significantly with the concentration of the RD3 photosensitizer and reached a peak at a concentration of 12.5MUM (p<0.05). The RSD3 and RBY photosensitizers had distinctly lower phototoxic effects in comparison to RD3. CONCLUSION: The RD3 photosensitizer showed a phototoxic effect on F. nucleatum and P. gingivalis. The results suggest that the application of the RD3 photosensitizer under visible light may be helpful as an adjunct treatment approach to the inactivation of periodontopathogenic bacteria. PMID- 21036349 TI - [Meningitis by S. agalactiae in a non-pregnant immunocompetent woman]. PMID- 21036350 TI - The reproducibility of serum anti-Mullerian hormone in subfertile women: within and between patient variability. AB - Serum anti-Mullerian hormone concentrations vary significantly over time and this should be taken into account when tailoring treatment protocols for patients undergoing controlled ovarian hyperstimulation (COH). Compared with FSH, serum anti-Mullerian hormone may have greater discriminatory power because of its modest intrapatient variation and the larger interpatient variation. PMID- 21036351 TI - Androgen levels, insulin sensitivity, and early insulin response in women with polycystic ovary syndrome: a long-term follow-up study. AB - Thirty-four women with polycystic ovary syndrome who previously had participated in studies with intravenous glucose tolerance test and hyperinsulinemic, euglycemic clamp between 1987 and 1995 underwent anthropometric, endocrine (T and sex-hormone binding globulin serum concentration), and metabolic (intravenous glucose tolerance test, hyperinsulinemic, euglycemic clamp, and androgens) measurements. Free androgen levels and beta-cell function decreased over time in women with polycystic ovary syndrome, but insulin sensitivity remained unaltered. PMID- 21036353 TI - One-step receding horizon H(infinity) control for networked control systems with random delay and packet disordering. AB - The receding horizon H(infinity) control (RHHC) problem is investigated in this paper for a class of networked control systems (NCSs) with random delay and packet disordering. A new model is proposed to describe the NCS with random delay which may be larger than one sampling period. The random delay is modeled as a Markov chain while the closed-loop system is described as a Markovian jump system. Sufficient conditions for the closed-loop NCS to be stochastically stable and the performance index to be upper bounded are derived by using the receding optimization principle. Furthermore, by solving a semi-definite programming (SDP) with linear matrix inequalities (LMIs) constraint, a piecewise-constant receding horizon H(infinity) controller is obtained, and the designed piecewise-constant controller ensures that the closed-loop NCS achieves a prescribed H(infinity) disturbance attenuation level. Finally, an illustrative example is given to demonstrate the effectiveness of the proposed method. PMID- 21036352 TI - Inguinal uterus, fallopian tube, and ovary associated with adult Mayer-Rokitansky Kuster-Hauser syndrome. AB - OBJECTIVE: To report a case of Mayer-Rokitansky-Kuster-Hauser syndrome (MRKH) with a utero-ovarian inguinal hernia, and to present a review of the pertinent literature. DESIGN: Case report and literature review. SETTING: Hospital clinic. PATIENT(S): A 31-year-old married woman. INTERVENTION(S): Ultrasound, magnetic resonance imaging, intravenous pyelography, hormone analysis, peripheral karyotyping, ovarian biopsy, repositioning of the uterus, fallopian tube, and ovary, herniorrhaphy, and Williams vulvovaginoplasty. MAIN OUTCOME MEASURE(S): Accuracy of diagnosis, preservation of ovarian function, hernia repair and creation of neovagina. RESULT(S): Our patient represented an adult case of MRKH syndrome associated with renal abnormality and utero-ovarian inguinal hernia. Our English-language literature search for similar well-documented cases revealed only two. Our management consisted of thorough counseling, and successful one step ovarian biopsy, repositioning of the uterus, fallopian tube, and ovary, herniorrhaphy, and Williams vulvovaginoplasty. CONCLUSION(S): This is the third case of adult 46,XX MRKH with utero-ovarian inguinal hernia in the English literature. Genital repositioning is mandatory to avoid torsion and preserve ovarian function. The choice of the type of hernia repair and vaginoplasty or any other procedure should be individualized to the patient's medical status. PMID- 21036354 TI - Traumatic brain injury and severe uncontrolled haemorrhage with short delay pre hospital resuscitation in a swine model. AB - INTRODUCTION: Unavailability of blood (and oxygen delivery) for pre-hospital resuscitation in haemorrhagic shock patients are major problems, supporting the importance for novel resuscitation strategies. In a combined polytrauma model of uncontrolled haemorrhage and traumatic brain injury (TBI) in swine, we investigated if pre-hospital administration of the haemoglobin based oxygen carrier HBOC-201 will improve tissue oxygenation and physiologic parameters compared to Lactated Ringer's (LR) solution. MATERIALS AND METHODS: Anaesthetised Yorkshire swine underwent fluid-percussion TBI and Grade III liver laceration. During a 30-min pre-hospital phase, the animals were resuscitated with a single infusion of HBOC-201, LR solution, or nothing (NON). Upon hospital arrival, the animals were given blood or normal saline as needed. Surviving animals were euthanised 6h post-injury. Cerebral blood flow was measured by microsphere injection, and pathology was assessed by gross observation and immunohistochemical analysis. RESULTS: Mean TBI force (2.4+/-0.1atm) (means+/ standard error of the mean) and blood loss (22.5+/-1.7mL/kg) were similar between groups. Survival at the 6h endpoint was similar in all groups (~50%). Cerebral perfusion pressure (CPP) and brain tissue oxygen tension were significantly greater in HBOC-201 as compared with LR animals (p<0.005). Mean arterial pressure (MAP) and mean pulmonary artery pressure (MPAP) were not significantly different amongst groups. Blood transfusion requirements were delayed in HBOC-201 animals. Animals treated with HBOC-201 or LR showed no immunohistopathological differences in glial fibrillary acidic protein (GFAP) and microtubule-associated protein 2 (MAP-2). Severity of subarachnoid and intraparenchymal haemorrhages were similar for HBOC and LR groups. CONCLUSION: In this polytrauma swine model of uncontrolled haemorrhage and TBI with a 30-min delay to hospital arrival, pre hospital resuscitation with one bolus of HBOC-201 indicated short term benefits in systemic and cerebrovascular physiological parameters. True clinical benefits of this strategy need to be confirmed on TBI and haemorrhagic shock patients. PMID- 21036355 TI - Impact of atorvastatin and omega-3 ethyl esters 90 on plasma plant sterol concentrations and cholesterol synthesis in type 2 diabetes: a randomised placebo controlled factorial trial. AB - OBJECTIVE: To determine the effects of statin treatment and omega-3 polyunsaturated fatty acid supplementation on plasma plant sterol concentrations and cholesterol synthesis in patients with type 2 diabetes. METHODS: Plant sterol concentrations and lanosterol (a marker of cholesterol synthesis) were measured using a high sensitivity assay to assess the effect of double-blind daily treatment for 4 months with atorvastatin 20mg or placebo and, in a 2 * 2 factorial design, omega-3 ethyl esters 90 2g or placebo. RESULTS: 658 patients were included in a per protocol analysis. The 4 treatment groups had similar mean [SD] age (63.5 years [11.7]), HbA(1c) (6.9% [1.1]) and diabetes duration (median 4 years [inter-quartile range 2, 8]). Atorvastatin treatment alone reduced low density lipoprotein (LDL) cholesterol by 1.4 mmol/l (44%, p<0.001), triglycerides by 0.3 mmol/l (20%, p<0.0001) and lanosterol by 0.36 MUmol/l (72%, p<0.001). There was no significant placebo adjusted change in median [95% confidence intervals] total plant sterol concentrations (-0.77 MUmol/l [inter-quartile range -2.13, 0.59]), although they were increased significantly with omega-3-acid EE90 treatment (3.23 MUmol/l [1.28, 5.17]). There was a 27% smaller reduction in LDL cholesterol with atorvastatin treatment in low cholesterol synthesisers with high absorption, defined by changes at or above the median lanosterol and campesterol levels, respectively, compared with the obverse group (difference 0.42 mmol/l [0.21, 0.62]). CONCLUSION: Treatment with atorvastatin in type 2 diabetes did not change median total plasma plant sterol concentrations, but LDL cholesterol was reduced most efficaciously in high cholesterol synthesisers with low intestinal cholesterol absorption. CLINICAL TRIAL REGISTRATION INFORMATION: Current controlled trials number ISRCTN: 76737502 (http://isrctn.org). PMID- 21036356 TI - Beyond C-reactive protein; new evidence for another inflammatory biomarker predicting cardiovascular disease risk. PMID- 21036357 TI - Macrophage endoplasmic reticulum (ER) proteins and reducing elements stabilize paraoxonase 2 (PON2). AB - OBJECTIVE: To analyze the ability of macrophage sub-cellular fractions to stabilize paraoxonase 2 (PON2). METHODS: Nuclei, mitochondria, lysosomes, endoplasmic reticulum (ER) and cytosol were isolated from J774A.1 macrophage cell line and incubated with recombinant PON2. RESULTS: Among the fractions analyzed the ER contains the highest PON2 lactonase activity, and was the most potent one in stabilizing recombinant PON2 (rePON2). Whereas control rePON2 activity was decreased by 40% after 20 h of incubation at 37 degrees C, in the presence of ER it decreased by only 15%. This effect could be attributed to the ER aqueous phase, and not to the ER lipids. The ER proteins fraction was responsible for PON2 stabilization, since heated ER or proteinase K-treated ER was not able to protect rePON2 from inactivation, while the protein fraction (after ammonium sulfate precipitation) completely prevented rePON2 inactivation. Since in the macrophage ER, there are increased levels of NADPH, secondary to glutathione reductase deficiency, we next studied the effect of the redox environment on PON2 inactivation. Incubation of rePON2 with DTT protected PON2 from inactivation. Similarly, NADPH, but not NADP, significantly increased rePON2 lactonase activity by up to 19%, after 20h of incubation as compared to control rePON2. Unlike ER from non-treated macrophages, ER harvested from oxidized-, or from cholesterol loaded-macrophages showed a significant lower basal PON2 lactonase activity, and did not protect PON2 from inactivation but rather increased it. CONCLUSION: Under normal conditions macrophage ER stabilizes PON2 activity, and this effect could be attributed to ER proteins and redox status. PMID- 21036358 TI - The behavior of the micro-mechanical cement-bone interface affects the cement failure in total hip replacement. AB - In the current study, the effects of different ways to implement the complex micro-mechanical behavior of the cement-bone interface on the fatigue failure of the cement mantle were investigated. In an FEA-model of a cemented hip reconstruction the cement-bone interface was modeled and numerically implemented in four different ways: (I) as infinitely stiff, (II) as infinitely strong with a constant stiffness, (III) a mixed-mode failure response with failure in tension and shear, and (IV) realistic mixed mode behavior obtained from micro-FEA models. Case II, III, and IV were analyzed using data from a stiff and a compliant micro FEA model and their effects on cement failure were analyzed. The data used for Case IV was derived from experimental specimens that were tested previously. Although the total number of cement cracks was low for all cases, the compliant Case II resulted in twice as many cracks as Case I. All cases caused similar stress distributions at the interface. In all cases, the interface did not display interfacial softening; all stayed the elastic zone. Fatigue failure of the cement mantle resulted in a more favorable stress distribution at the cement bone interface in terms of less tension and lower shear tractions. We conclude that immediate cement-bone interface failure is not likely to occur, but its local compliancy does affect the formation of cement cracks. This means that at a macro-level the cement-bone interface should be modeled as a compliant layer. However, implementation of interfacial post-yield softening does seems to be necessary. PMID- 21036359 TI - Multiscale modeling of bone tissue with surface and permeability control. AB - Natural biological materials usually present a hierarchical arrangement with various structural levels. The biomechanical behavior of the complex hierarchical structure of bone is investigated with models that address the various levels corresponding to different scales. Models that simulate the bone remodeling process concurrently at different scales are in development. We present a multiscale model for bone tissue adaptation that considers the two top levels, whole bone and trabecular architecture. The bone density distribution is calculated at the macroscale (whole bone) level, and the trabecular structure at the microscale level takes into account its mechanical properties as well as surface density and permeability. The bone remodeling process is thus formulated as a material distribution problem at both scales. At the local level, the biologically driven information of surface density and permeability characterizes the trabecular structure. The model is tested by a three-dimensional simulation of bone tissue adaptation for the human femur. The density distribution of the model shows good agreement with the actual bone density distribution. Permeability at the microstructural level assures interconnectivity of pores, which mimics the interconnectivity of trabecular bone essential for vascularization and transport of nutrients. The importance of this multiscale model relays on the flexibility to control the morphometric parameters that characterize the trabecular structure. Therefore, the presented model can be a valuable tool to define bone quality, to assist with diagnosis of osteoporosis, and to support the development of bone substitutes. PMID- 21036360 TI - Preparation and evaluation of solid-phase microextraction fiber based on nano structured copolymer of aniline and m-amino benzoic acid coating for the analysis of fatty acids in zooplanktons. AB - A novel nano-structured copolymer of aniline and m-amino benzoic acid (m-ABA) was introduced as a coating of solid phase microextraction (SPME) of saturated-fatty acids in zooplanktons by coupling to gas chromatography-mass spectrometry (GC MS). The nano-structured coating was prepared using co-polymerization of m aminobenzoic acid and aniline. Improved temperature resistance (up to 350 degrees C), relatively improved life time (more than 50 times) and satisfactory extraction efficiency were obtained by insertion of carboxylate groups into the framework of polyaniline. Different extraction parameters such as extraction temperature, extraction time, ionic strength, stirring rate and headspace volume were investigated and optimized. Single fiber repeatability and fiber-to-fiber reproducibility were <5.7% and <10.2%, respectively and the limits of detection varied from 0.01 (C14:0) to 6.07 MUg L(-1) (C20:0). Correlation coefficients (R(2)) of the calibration curves ranged from 0.992 (C20:0) to 0.998 (C18:0) with a linearity from 0.5 to 200 MUg mL(-1). The recoveries obtained ranged from 83% (C16:0) to 115% (C14:0). PMID- 21036361 TI - Coupling protein complex analysis to peptide based proteomics. AB - Proteolysis is a central component of most proteomics methods. Unfortunately much of the information relating to the structural diversity of proteins is lost during digestion. This paper describes a method in which the native proteome of yeast was subjected to preliminary fractionation by size exclusion chromatography (SEC) prior to trypsin digestion of SEC fractions and reversed phase chromatography-mass spectral analysis to identify tryptic peptides thus generated. Through this approach proteins associated with other proteins in high molecular mass complexes were recognized and identified. A focus of this work was on the identification of Hub proteins that associate with multiple interaction partners. A critical component of this strategy is to choose methods and conditions that maximize retention of native structure during the various stages of analysis prior to proteolysis, especially during cell lysis. Maximum survival of protein complexes during lysis was obtained with the French press and bead beater methods of cell disruption at approximately pH 8 with 200 mM NaCl in the lysis buffer. Structure retention was favored by higher ionic strength, suggesting that hydrophobic effects are important in maintaining the structure of protein complexes. Recovery of protein complexes declined substantially with storage at any temperature, but storage at -20 degrees C was best when low temperature storage was necessary. Slightly lower recovery was obtained with storage at -80 degrees C while lowest recovery was achieved at 4 degrees C. It was concluded that initial fractionation of native proteins in cell lysates by SEC prior to RPC-MS/MS of tryptic digests can be used to recognize and identify proteins in complexes along with their interaction partners in known protein complexes. PMID- 21036362 TI - Qualitative and quantitative analysis of pyrolysis oil by gas chromatography with flame ionization detection and comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry. AB - Pyrolysis oils have attracted a lot of interest, as they are liquid energy carriers and general sources of chemicals. In this work, gas chromatography with flame ionization detector (GC-FID) and two-dimensional gas chromatography with time-of-flight mass spectrometry (GC*GC-TOFMS) techniques were used to provide both qualitative and quantitative results of the analysis of three different pyrolysis oils. The chromatographic methods and parameters were optimized and solvent choice and separation restrictions are discussed. Pyrolysis oil samples were diluted in suitable organic solvent and were analyzed by GC*GC-TOFMS. An average of 300 compounds were detected and identified in all three samples using the ChromaToF (Leco) software. The deconvoluted spectra were compared with the NIST software library for correct matching. Group type classification was performed by use of the ChromaToF software. The quantification of 11 selected compounds was performed by means of a multiple-point external calibration curve. Afterwards, the pyrolysis oils were extracted with water, and the aqueous phase was analyzed both by GC-FID and, after proper change of solvent, by GC*GC-TOFMS. As previously, the selected compounds were quantified by both techniques, by means of multiple point external calibration curves. The parameters of the calibration curves were calculated by weighted linear regression analysis. The limit of detection, limit of quantitation and linearity range for each standard compound with each method are presented. The potency of GC*GC-TOFMS for an efficient mapping of the pyrolysis oil is undisputable, and the possibility of using it for quantification as well has been demonstrated. On the other hand, the GC-FID analysis provides reliable results that allow for a rapid screening of the pyrolysis oil. To the best of our knowledge, very few papers have been reported with quantification attempts on pyrolysis oil samples using GC*GC-TOFMS most of which make use of the internal standard method. This work provides the ground for further analysis of pyrolysis oils of diverse sources for a rational design of both their production and utilization process. PMID- 21036363 TI - Optimization and validation of post-column assay for screening of radical scavengers in herbal raw materials and herbal preparations. AB - On-line method, which combines HPLC distribution and post-column reaction, was designed for the search of individual antioxidants. Optimization of the assay was performed evaluating optimal ABTS(+) radical cation concentration in the reactor, reaction time, impact of flow rate, reaction coil length. HPLC-ABTS assay validation in this work was performed by assessing reference antioxidant negative peak areas in radical scavenging chromatogram. Sample free radical scavenging activity is expressed as trolox equivalent antioxidant capacity (TEAC). Optimized and validated method was applied in detection of compounds possessing free radical scavenging ability in complex mixtures. Antioxidant compounds were studied in perilla (Perilla frutescens (L.) Britton var. crispa f. viridis) herbal raw material and its preparations. The HPLC-separated antioxidant compounds were identified using HPLC-photodiode array coupled to mass spectrometer, using a reference mass for determining accurate masses. Radical scavenging characteristics of rosmarinic acid, which is the dominant phenolic compound in medicinal herbal raw material of perilla and its preparations, were confirmed by the calculated TEAC values. Compounds responsible for antioxidant effect in herbal raw materials and herbal preparations were identified, evaluated and compared. PMID- 21036364 TI - Fabrication and characterization of bimetallic Pt-Au nanowires supported on FSM 16 and their catalytic activities toward water-gas shift reaction. AB - A facile, previously unexplored, method to synthesize bimetallic Pt-Au nanowires (20nm diameter*120-170nm long) on mesoporous FSM-16 (2.7nm) was fabricated by co impregnation of H(2)PtCl(6) with HAuCl(4) followed by evacuation at 300K and finally exposure to the CO/H(2)O gas mixture (60:5Torr) at 323K for 1.0h. On the other hand, spherical monometallic nanoparticles of pure Pt (7.0nm diameter) and Au (7-26nm diameter) were synthesized as well, by impregnation, at the same reaction conditions. The catalysts were characterized by in situ FTIR spectroscopy, UV-vis absorption spectroscopy, TEM, TPR and TPCOR. The catalytic activities toward the water-gas shift reaction (WGSR) were also examined under atmospheric pressure and at the margin of 323-373K. The optical absorption spectra showed a remarkable shift and broadening of Pt-Au surface Plasmon resonance band at 515nm apart from those of individual analogue emphasizing bimetallic formation. Results from in situ FTIR spectroscopy indicated that incorporation of Au assisted and stabilized the formation of carbonyl clusters of Pt-Au-CO (2084cm(-1)) and Pt-CO (1888cm(-1)) inside the host FSM-16. The Pt-Au carbonyl clusters built up at the moment of vanishing the linear carbonyl band of the charged Au (Au(+)-CO, 2186cm(-1)) along with a concomitant increase in the reduced gold (Au(0)-CO, 2124cm(-1)) species. TPR profiles showed that the H(2) consumed was higher for Pt/FSM-16 than for Pt-Au/FSM-16 verifying the facile reduction of Pt moieties after addition of Au. The CO adsorption peak maximum, in TPCOR, for Pt/FSM-16 occurred at higher temperature than that of Pt-Au/FSM-16, which exhibited higher amounts of CO(2) produced. The relative decrease in CO bindings on bimetallic surface was responsible for increasing the CO oxidation activity mainly through an association mechanism. Accordingly, the activity of Pt Au/FSM-16 towards WGS showed a marked increase (8-23 times) compared with those of monometallics emphasizing the dependence of this reaction on the electronic defects of the nanowires. A straightforward reduction mechanism was deduced for Pt-Au alloy formation in view of the results obtained. PMID- 21036365 TI - The size of particle aggregates produced by flocculation with PNIPAM, as a function of temperature. AB - This work investigates the effect of temperature on the size of alumina aggregates formed by flocculation with temperature responsive Poly(N Isopropylacrylamide)(PNIPAM). The results are discussed in terms of the effects of temperature on particle collision, particle adhesion and aggregate breakage. It was found that the size of alumina aggregates increases with increasing solution temperature. Particle/particle collision and aggregate breakage are largely unaffected by increasing solution temperature and therefore could not account for the change in aggregate size. The dominant factor in aggregate growth with increasing temperature was found to be the increase in the force of adhesion between alumina particles. The appearance of the adhesive force is triggered by the increase in temperature above the lower critical solution temperature of PNIPAM. PMID- 21036366 TI - Charging of silver bromide aqueous interface: Evaluation of enthalpy and entropy of interfacial reactions from surface potential data. AB - Dependence of surface potential (electrostatic potential at the inner Helmholtz plane, Psi(0)) at the silver bromide aqueous electrolyte interface was measured as a function of the activities of Br(-) and Ag(+) by using a single crystal silver bromide electrode (SCr-AgBr). Absolute values of surface potentials were obtained from electrode potentials of SCr-AgBr and isoelectric points. Measurements were performed at different temperatures in the range from 10 to 50 degrees C. Corresponding equilibrium constants of interfacial reactions were obtained using the surface complexation model and interpreted via the van't Hoff equation. As a result of the interpretation for the binding of bromide ions leading to a negative surface charge, the thermodynamic parameters obtained were Delta(n)H(?)=-33kJmol(-1) and Delta(n)S(?)=-31Jmol(-1)K(-1); and for the binding of silver ions leading to a positive surface charge, Delta(p)H(?)=-72kJmol(-1) and Delta(p)S(?)=-196Jmol(-1)K(-1). Association of counterions (CI) with oppositely charged surface sites partially compensates the surface charge. Assuming approximately the same affinities for anions (NO(3)(-)) and cations (K(+)) thermodynamic parameters for their binding were obtained as Delta(CI)H(?)~7kJmol(-1) and Delta(CI)S(?)~105Jmol(-1)K(-1). PMID- 21036367 TI - Superhydrophilic and antireflective La(OH)(3)/SiO(2)-nanorod/nanosphere films. AB - La(OH)(3) nanorods were self-stacked on the glass slide substrates using an aqueous suspension obtained from the hydrolysis of LaOCl. The key for producing a high optical quality film of La(OH)(3) lies in the preparation of an aqueous suspension in which La(OH)(3) nanorods are well dispersed. These thin-film coatings of La(OH)(3) nanorods led to a significantly reduced reflective losses in the visible region, exhibiting an attractive and potentially useful single layer antireflection property. Furthermore, La(OH)(3) nanorod layer provides a sufficiently porous and rough surface required to achieve superhydrophilicity. Thus, when SiO(2) nanoparticles of ca. 20nm in diameter were deposited onto La(OH)(3) layer of high roughness, the resulting La(OH)(3)/SiO(2) film demonstrated an interesting nanoporosity-derived superhydrophilicity and antifogging property with no significant loss of antireflective property. PMID- 21036368 TI - Fate of nonreplaced sinuses of Valsalva in bicuspid aortic valve disease. AB - OBJECTIVE: There is growing consensus that the ascending aorta should be replaced at the time of aortic valve replacement for bicuspid aortic valve even if it is only moderately dilated; the natural history of nonreplaced sinuses of Valsalva is less clear. METHODS: We identified patients without defined connective tissue disorder undergoing primary aortic valve replacement for bicuspid aortic valve and separate repair of the ascending aorta without root replacement at the Mayo Clinic between January 1, 1988, and December 31, 2007. RESULTS: Among 218 patients, 65 underwent ascending aortoplasty and 153 underwent separate graft replacement of the ascending aorta. Of the latter group, 15 also had graft replacement of the noncoronary sinus. The mean age at operation was 62 +/- 13 years. Valvular dysfunction was predominantly stenosis in 151 patients (70%), regurgitation in 54 patients (25%), and mixed in 12 patients (5%). At a follow-up of up to 17 years (median, 3.3 years; range, 0-17 years), 10 patients (5%) had undergone late reoperation, of whom 1 had replacement of the ascending aorta and 1 had replacement of the root for significant dilatation of the sinuses. Both patients had originally undergone aortoplasty. No other patient required root surgery. One-, 5-, and 10-year freedom from reoperation for any cause were 97.6%, 94.9%, and 85.5%, respectively. CONCLUSIONS: Although progressive ascending aortic dilatation after aortic valve replacement for bicuspid aortic valve is well documented, progressive dilatation of nonreplaced sinuses is not evident. Separate valve and graft repair remains a reasonable surgical option in the setting of aortic valve replacement for bicuspid aortic valve with ascending aortic dilatation provided the sinuses of Valsalva are not significantly enlarged. PMID- 21036369 TI - Less invasive versus conventional double-valve surgery: a propensity-matched comparison. AB - OBJECTIVE: Less invasive approaches to double-valve surgery are used for improved cosmesis; however, few studies have investigated their effect on outcome. We sought to compare these less invasive approaches with conventional full sternotomy. METHODS: From January 1995 to January 2004, 114 patients underwent primary double-valve surgery through a less invasive approach and 381 through conventional sternotomy. Because there were important differences in the patients' characteristics, a propensity score based on 42 factors was used to obtain 81 well-matched patient pairs (71% of possible matches) for comparison of in-hospital morbidity and mortality, mediastinal drainage, transfusion requirements, pulmonary function, pain, and long-term survival. RESULTS: In hospital mortality was similar for propensity-matched patients: 6.2% (5/81) for those undergoing less invasive surgery and 2.5% (2/81) for those undergoing conventional sternotomy (P > .4). Occurrences of stroke (P > .9), renal failure (P = .4), myocardial infarction (P > .9), and infection (P > .9) were also similar. However, 24-hour mediastinal drainage was less after less invasive surgery (median, 250 vs 400 mL; P < .0001), but a similar proportion of patients received transfusions (28% vs 40%, P = .2). An equivalent proportion of patients were extubated in the operating room (7.7% vs 7.0%, P > .9), and median hours to extubation were similar (5.0 vs 6.5 hours). Pain scores were equivalent (P > .3). Long-term survival was also similar (82% and 76% at 10 years, P = .07). CONCLUSIONS: Within that portion of the spectrum of double-valve surgery in which propensity matching was possible, less invasive surgery had cosmetic and blood product use advantages over conventional surgery and no apparent detriments. PMID- 21036370 TI - C-index is associated with functional outcomes after laparoscopic partial nephrectomy. AB - PURPOSE: The C-index is a morphometric descriptor of renal masses that incorporates tumor size and site. We examined associations of the C-index with kidney function after laparoscopic partial nephrectomy. MATERIALS AND METHODS: We retrospectively reviewed the records of 131 patients who underwent laparoscopic partial nephrectomy for a single kidney tumor. We calculated the C-index from preoperative contrast enhanced computerized tomography images. Estimated glomerular filtration rate was calculated using the modification of diet in renal disease 2 equation. Nadir estimated glomerular filtration rate was calculated using peak serum creatinine within 7 days of surgery. RESULTS: The median C-index was 2.7 (range 0.7 to 9.6). The median preoperative and nadir estimated glomerular filtration rate was 78 (range 23 to 148) and 54 ml/minute/1.73 m2 (range 15 to 127, p<0.001). The mean+/-SD total glomerular filtration rate decrease was 28%+/-16%. On univariate analysis we noted a positive correlation between log C-index and the nadir estimated glomerular filtration rate (r=0.29, p=0.002), and a negative correlation between log C-index and the percent decrease in the estimated glomerular filtration rate (r=-0.4, p<0.001). On multivariate analysis the estimated glomerular filtration rate percent decrease was significantly associated with log C-index (p=0.005) and warm ischemia time (p<0.001) but not with tumor diameter or the preoperative estimated glomerular filtration rate. Of patients with a C-index of 2.5 or less 70% showed a 30% or greater decrease in the estimated glomerular filtration rate vs 32% of those with a C-index of greater than 2.5 (RR 2.2, p<0.001). CONCLUSIONS: The C-index is associated with the postoperative nadir estimated glomerular filtration rate and the percent decrease in the estimated glomerular filtration rate after laparoscopic partial nephrectomy. A C-index of less than 2.5 correlated with a 2.2-fold increased risk of a 30% or greater estimated glomerular filtration rate decrease after laparoscopic partial nephrectomy. PMID- 21036371 TI - Editorial comment. PMID- 21036372 TI - Ingestion of marine debris by loggerhead sea turtles, Caretta caretta, in the Adriatic Sea. AB - We examined the occurrence of marine debris in the gastrointestinal tract of 54 loggerhead sea turtles (Caretta caretta) found stranded or incidentally captured dead by fisheries in the Adriatic Sea, with a curved carapace length of 25.0-79.2 cm. Marine debris was present in 35.2% of turtles and included soft plastic, ropes, Styrofoam and monofilament lines found in 68.4%, 42.1%, 15.8% and 5.3% of loggerheads that have ingested debris, respectively. The dry mass of debris per turtle was low, ranging from <0.01 to 0.71 g, and the ingestion was not significantly affected by sex or body size (all p>0.05). Marine debris averaged 2.2 +/- 8.0% of dry mass of gut content, with a maximum of 35% found in a juvenile turtle that most likely died due to debris ingestion. Considering the relatively high occurrence of debris intake and possible sub-lethal effects of even small quantities of marine debris, this can be an additional factor of concern for loggerheads in the Adriatic Sea. PMID- 21036373 TI - Low-salt diet increases insulin resistance in healthy subjects. AB - Low-salt (LS) diet activates the renin-angiotensin-aldosterone and sympathetic nervous systems, both of which can increase insulin resistance (IR). We investigated the hypothesis that LS diet is associated with an increase in IR in healthy subjects. Healthy individuals were studied after 7 days of LS diet (urine sodium <20 mmol/d) and 7 days of high-salt (HS) diet (urine sodium >150 mmol/d) in a random order. Insulin resistance was measured after each diet and compared statistically, unadjusted and adjusted for important covariates. One hundred fifty-two healthy men and women, aged 39.1 +/- 12.5 years (range, 18-65) and with body mass index of 25.3 +/- 4.0 kg/m(2), were included in this study. Mean (SD) homeostasis model assessment index was significantly higher on LS compared with HS diet (2.8 +/- 1.6 vs 2.4 +/- 1.7, P < .01). Serum aldosterone (21.0 +/- 14.3 vs 3.4 +/- 1.5 ng/dL, P < .001), 24-hour urine aldosterone (63.0 +/- 34.0 vs 9.5 +/- 6.5 MUg/d, P < .001), and 24-hour urine norepinephrine excretion (78.0 +/- 36.7 vs 67.9 +/- 39.8 MUg/d, P < .05) were higher on LS diet compared with HS diet. Low-salt diet was significantly associated with higher homeostasis model assessment index independent of age, sex, blood pressure, body mass index, serum sodium and potassium, serum angiotensin II, plasma renin activity, serum and urine aldosterone, and urine epinephrine and norepinephrine. Low-salt diet is associated with an increase in IR. The impact of our findings on the pathogenesis of diabetes and cardiovascular disease needs further investigation. PMID- 21036374 TI - Metabolism of primed, constant infusions of [1,2-13C2] glycine and [1-13C1] phenylalanine to urinary oxalate. AB - Experiments in humans and rodents using oral doses of glycine and phenylalanine have suggested that the metabolism of these amino acids contributes to urinary oxalate excretion. To better define this contribution, we have examined the primed, constant infusion of [1-(13)C(1)] phenylalanine and [1,2-(13)C(2)] glycine in the postabsorptive state in healthy adults. Subjects were infused for 5 hours, hourly urines were collected, and blood was drawn every 30 minutes. Ion chromatography/mass spectrometry was used to measure [(13)C] enrichment in urinary oxalate, glycolate, and hippurate; and the enrichment of (13)C-amino acids in plasma samples was measured by gas chromatography/mass spectrometry. Following infusion with either 6 MUmol/(kg h) [1-(13)C(1)] phenylalanine or 6 MUmol/(kg h) [1,2-(13)C(2)] glycine, no isotopic glycolate or oxalate was detected in urine. Based on the limits of detection of our ion chromatography/mass spectroscopy method, these data indicate that less than 0.7% of the urinary oxalate could be derived from phenylalanine catabolism and less than 5% from glycine catabolism. Infusions with high levels of [1,2-(13)C(2)] glycine, 60 MUmol/(kg h), increased mean plasma glycine by 29% and the whole-body flux of glycine by 72%. Under these conditions, glycine contributed 16.0% +/- 1.6% and 16.6% +/- 3.2% to urinary oxalate and glycolate excretion, respectively. Experiments using cultured hepatoma cells demonstrated that only at supraphysiological levels (>1 mmol/L) did glycine and phenylalanine metabolism increase oxalate synthesis. These data suggest that glycine and phenylalanine metabolism make only minor contributions to oxalate synthesis and urinary oxalate excretion. PMID- 21036375 TI - Indolyl-3-acetaldoxime dehydratase from the phytopathogenic fungus Sclerotinia sclerotiorum: purification, characterization, and substrate specificity. AB - The purification and characterization of indolyl-3-acetaldoxime dehydratase produced by the plant fungal pathogen Sclerotinia sclerotiorum is described. The substrate specificity indicates that it is an indolyl-3-acetaldoxime dehydratase (IAD, EC 4.99.1.6), which catalyzes transformation of indolyl-3-acetaldoxime to indolyl-3-acetonitrile. The enzyme showed Michaelis-Menten kinetics and had an apparent molecular mass of 44 kDa. The amino acid sequence of IAD, determined using LC-ESI-MS/MS, identified it as the protein SS1G_01653 from S. sclerotiorum. IADSs was highly homologous (84% amino acid identity) to the hypothetical protein BC1G_14775 from Botryotinia fuckeliana B05.10. In addition, similarity to the phenylacetaldoxime dehydratases from Gibberella zeae (33% amino acid identity) and Bacillus sp. (20% amino acid identity) was noted. The specific activity of IADSs increased about 17-fold upon addition of Na(2)S(2)O(4) under anaerobic conditions, but in the absence of Na(2)S(2)O(4) no significant change was observed, whether aerobic or anaerobic conditions were used. As with other aldoxime dehydratases isolated from microbes, the role of IADSs in fungal plant pathogens is not clear, but given its substrate specificity, it appears unlikely that IADSs is a general xenobiotic detoxifying enzyme. PMID- 21036376 TI - Comparison of lidocaine, tramadol, and lidocaine-tramadol for epidural analgesia in lambs. AB - Epidural anesthesia is commonly utilized in veterinary medicine to allow diagnostic, obstetrical, and surgical intervention, in the perineal region of domestic animal. The following study was carried out to directly compare the time of onset and duration of anesthesia produced by a tramadol and lidocaine-tramadol combination with that produced by lidocaine administration in the epidural space of lamb. Seven healthy female lambs of undefined breed weighing 15-20 kg were selected for this study. Epidural anesthesia was produced in all lambs by 2% lidocaine and with 2 weeks intervals repeated by combination of lidocaine tramadol and tramadol alone. Analgesia was defined as lack of a response to pin prick test and pressure from hemostat clamp (closed to the first ratchet) applied first in the perineal area and then moved cranially toward the thoracic region until a response (movement associated with pin prick test or hemostat pressure) was observed. Time to onset, duration and cranial spread of analgesia were recorded. Heart rate (HR), respiratory rate (RR), and rectal temperature were recorded before (baseline, 0) and at 15, 30, 45, 60, 75, 90, 105 and 120 min after epidural administration of the solution. The results were expressed as mean +/- SD and were analyzed by a one-way analysis of variance and Duncan's test as a post hoc for heart rate, respiratory rate and body temperature and also, for time of onset and duration of analgesia. Graphpad Prism version 5 software program was used for all analyses. A value of P<0.05 was considered significant. The tramadol produced a significant (P<0.05) longer duration of analgesia than lidocaine alone and lidocaine-tramadol combination. Also, lidocaine-tramadol combination produced a significant (P<0.05) longer duration of analgesia than lidocaine alone. Complete analgesia began more delayed in the tramadol treatment than lidocaine tramadol and lidocaine alone. The combination of lidocaine-tramadol produced analgesia of longer duration than lidocaine and onset time was approximately same as lidocaine group. PMID- 21036377 TI - MCT1, MCT4 and CD147 gene polymorphisms in healthy horses and horses with myopathy. AB - Polymorphisms in human lactate transporter proteins (monocarboxylate transporters; MCTs), especially the MCT1 isoform, can affect lactate transport activity and cause signs of exercise-induced myopathy. Muscles express MCT1, MCT4 and CD147, an ancillary protein, indispensable for the activity of MCT1 and MCT4. We sequenced the coding sequence (cDNA) of horse MCT4 for the first time and examined polymorphisms in the cDNA of MCT1, MCT4 and CD147 of 16 healthy horses. To study whether signs of myopathy are linked to the polymorphisms, biopsy samples were taken from 26 horses with exercise-induced recurrent myopathy. Two polymorphisms that cause a change in amino acid sequence were found in MCT1 (Val(432)Ile and Lys(457)Gln) and one in CD147 (Met(125)Val). All polymorphisms in MCT4 were silent. Mutations in MCT1 or CD147 in equine muscle were not associated with myopathy. In the future, a functional study design is needed to evaluate the physiological role of the polymorphisms found. PMID- 21036378 TI - Randomised trial of face-washing to develop a standard definition of a clean face for monitoring trachoma control programmes. AB - Surgery, antibiotics, facial cleanliness and environmental improvements (SAFE) are recommended for trachoma control. Programmes assess clean faces in children, but no standard definition of a clean face exists. We conducted a randomised controlled trial of face-washing to develop a valid and repeatable definition of a clean face. A total of 424 children were randomised to washed and unwashed groups after a first observation. Three additional observations were made throughout the day. Photographs were taken at each observation. No difference was observed in wet nasal discharge, dust, food or flies on the face between the face washed and unwashed groups at baseline or after washing. A difference was observed in the presence of ocular discharge (P < 0.001) and dry nasal discharge (P < 0.001) after washing. Agreement among observers was highest for flies (Kappa = 0.89, 95% CI = 0.87-0.91), followed by nasal (Kappa = 0.64, 0.62-0.66) and ocular (Kappa = 0.48, 0.46-0.50) discharge. The ability of any definition to identify whether a face had been washed decreased at each observation. This study suggests that the absence of ocular and dry nasal discharge can be used as an indicator of 'clean face', although it is not a good predictor of whether a face has been washed and is difficult to recommend. PMID- 21036379 TI - Antiviral activities of ISG20 in positive-strand RNA virus infections. AB - ISG20 is an interferon-inducible 3'-5' exonuclease that inhibits replication of several human and animal RNA viruses. However, the specificities of ISG20's antiviral action remain poorly defined. Here we determine the impact of ectopic expression of ISG20 on replication of several positive-strand RNA viruses from distinct viral families. ISG20 inhibited infections by cell culture-derived hepatitis C virus (HCV) and a pestivirus, bovine viral diarrhea virus and a picornavirus, hepatitis A virus. Moreover, ISG20 demonstrated cell-type specific antiviral activity against yellow fever virus, a classical flavivirus. Overexpression of ISG20, however, did not inhibit propagation of severe acute respiratory syndrome coronavirus, a highly-pathogenic human coronavirus in Huh7.5 cells. The antiviral effects of ISG20 were all dependent on its exonuclease activity. The closely related cellular exonucleases, ISG20L1 and ISG20L2, did not inhibit HCV replication. Together, these data may help better understand the antiviral specificity and action of ISG20. PMID- 21036381 TI - Completely assembled virus particles detected by transmission electron microscopy in proximal and mid-axons of neurons infected with herpes simplex virus type 1, herpes simplex virus type 2 and pseudorabies virus. AB - The morphology of alphaherpesviruses during anterograde axonal transport from the neuron cell body towards the axon terminus is controversial. Reports suggest that transport of herpes simplex virus type 1 (HSV-1) nucleocapsids and envelope proteins occurs in separate compartments and that complete virions form at varicosities or axon termini (subassembly transport model), while transport of a related alphaherpesvirus, pseudorabies virus (PRV) occurs as enveloped capsids in vesicles (assembled transport model). Transmission electron microscopy of proximal and mid-axons of primary superior cervical ganglion (SCG) neurons was used to compare anterograde axonal transport of HSV-1, HSV-2 and PRV. SCG cell bodies were infected with HSV-1 NS and 17, HSV-2 2.12 and PRV Becker. Fully assembled virus particles were detected intracellularly within vesicles in proximal and mid-axons adjacent to microtubules after infection with each virus, indicating that assembled virions are transported anterograde within axons for all three alphaherpesviruses. PMID- 21036382 TI - Feature selection methods for characterizing and classifying adaptive Sustainable Flood Retention Basins. AB - The European Union's Flood Directive 2007/60/EC requires member states to produce flood risk maps for all river basins and coastal areas at risk of flooding by 2013. As a result, flood risk assessments have become an urgent challenge requiring a range of rapid and effective tools and approaches. The Sustainable Flood Retention Basin (SFRB) concept has evolved to provide a rapid assessment technique for impoundments, which have a pre-defined or potential role in flood defense and diffuse pollution control. A previous version of the SFRB survey method developed by the co-author Scholz in 2006 recommends gathering of over 40 variables to characterize an SFRB. Collecting all these variables is relatively time-consuming and more importantly, these variables are often correlated with each other. Therefore, the objective is to explore the correlation among these variables and find the most important variables to represent an SFRB. Three feature selection techniques (Information Gain, Mutual Information and Relief) were applied on the SFRB data set to identify the importance of the variables in terms of classification accuracy. Four benchmark classifiers (Support Vector Machine, K-Nearest Neighbours, C4.5 Decision Tree and Naive Bayes) were subsequently used to verify the effectiveness of the classification with the selected variables and automatically identify the optimal number of variables. Experimental results indicate that our proposed approach provides a simple, rapid and effective framework for variable selection and SFRB classification. Only nine important variables are sufficient to accurately classify SFRB. Finally, six typical cases were studied to verify the performance of the identified nine variables on different SFRB types. The findings provide a rapid scientific tool for SFRB assessment in practice. Moreover, the generic value of this tool allows also for its wide application in other areas. PMID- 21036383 TI - Transcriptome analysis provides insights for understanding the adverse effects of endosulfan in Drosophila melanogaster. AB - Indiscriminate use of agrochemicals worldwide, particularly, persistent organic pollutants (POPs), is of concern. Endosulfan, a POP, is used by various developing/developed nations and is known to adversely affect the development and the hormonal profiles of humans and animals. However, little is known about the molecular players/pathways underlying the adverse effects of endosulfan. We therefore analyzed the global gene expression changes and subsequent adverse effects of endosulfan using Drosophila. We used Drosophila melanogaster keeping in view of its well annotated genome and the wealth of genetic/molecular reagents available for this model organism. We exposed third instar larvae of D. melanogaster to endosulfan (2.0 MUg mL(-1)) for 24 h and using microarray, we identified differential expression of 256 genes in exposed organisms compared to controls. These genes are associated with cellular processes such as development, stress and immune response and metabolism. Microarray results were validated through quantitative PCR and biochemical assay on a subset of genes/proteins. Taking cues from microarray data, we analyzed the effect of endosulfan on development, emergence and survival of the organism. In exposed organisms, we observed deformities in hind-legs, reminiscent of those observed in higher organisms exposed to endosulfan. In addition, we observed delayed and/or reduced emergence in exposed organisms when compared to their respective controls. Together, our studies not only highlight the adverse effects of endosulfan on the organism but also provide an insight into the possible genetic perturbations underlying these effects, which might have potential implications to higher organisms. PMID- 21036380 TI - Identification of amino acid substitutions associated with neutralization phenotype in the human immunodeficiency virus type-1 subtype C gp120. AB - Neutralizing antibodies (Nabs) are thought to play an important role in prevention and control of HIV-1 infection and should be targeted by an AIDS vaccine. It is critical to understand how HIV-1 induces Nabs by analyzing viral sequences in both tested viruses and sera. Neutralization susceptibility to antibodies in autologous and heterologous plasma was determined for multiple Envs (3-6) from each of 15 subtype-C-infected individuals. Heterologous neutralization was divided into two distinct groups: plasma with strong, cross-reactive neutralization (n=9) and plasma with weak neutralization (n=6). Plasma with cross reactive heterologous Nabs also more potently neutralized contemporaneous autologous viruses. Analysis of Env sequences in plasma from both groups revealed a three-amino-acid substitution pattern in the V4 region that was associated with greater neutralization potency and breadth. Identification of such potential neutralization signatures may have important implications for the development of HIV-1 vaccines capable of inducing Nabs to subtype C HIV-1. PMID- 21036384 TI - Black carbon (BC) in urban and surrounding rural soils of Beijing, China: spatial distribution and relationship with polycyclic aromatic hydrocarbons (PAHs). AB - The concentrations of black carbon (BC), total organic carbon (TOC) and polycyclic aromatic hydrocarbons (PAHs) have been determined in soils from urban and rural areas of Beijing. The rural area can be divided into plain and mountainous areas which are close to and relatively far from the urban area, respectively. Concentration of BC (5.83 +/- 3.05 mg g-1) and BC/TOC concentration ratio (0.37 +/- 0.15) in Beijing's urban soil are high compared with that in world background soils and rural soils of Beijing, suggesting the urban environment to be an essential source and sink of BC. Concentration of BC in the urban area decreases from the inner city to exterior areas, which correlates with the urbanization history of Beijing and infers accumulation of BC in old urban soils. Black carbon in Beijing soils mainly comes from fossil fuel combustion, especially traffic emission. Median PAH concentration in the urban area (502 ng g 1) is one order of magnitude higher than that in the rural plain (148 ng g-1) and mountainous area (146 ng g-1) where PAHs are supposed to mainly come from atmospheric deposition from the urban area. Concentrations of BC correlate significantly with those of PAHs (p < 0.01, except naphthalene) in the urban area and with those of heavier 4-, 5- and 6- ring PAHs (p < 0.01) in the adjacent rural plain area, while there is no significant correlation with any PAH in the farther rural mountainous area. PMID- 21036385 TI - Strontium isotopes in Melanopsis sp. as indicators of variation in hydrology and climate in the Upper Jordan Valley during the Early-Middle Pleistocene, and wider implications. AB - Aquifers dominated by Pleistocene basalts and Jurassic to Cretaceous calcareous rocks feed the Hula basin which is drained by the Jordan River into Lake Kinneret. The sedimentary sequence of Lower-Middle Pleistocene Benot Ya'akov Formation (BYF) exposed by excavations of the 0.78 Ma lake-side site of Gesher Benot Ya'aqov (GBY) consists of six cycles representing ca. 100 ka history of the Hula basin. This study characterizes the types of water sources in the catchment, tests the use of the Strontium (Sr) isotopes in the common extant snail Melanopsis sp. as a tracer for water in its habitat, and uses this tracer in the fossil specimens from GBY to investigate the palaeohydrology of the Hula paleolake during the corresponding period. The Sr isotope composition ((87)Sr/(86)Sr) of extant Melanopsis shells in the Hula catchment range widely (0.7046-0.7079). These analyses define distinct groups of water sources and aquifers, while the Jordan River at the GBY site has values around 0.70685. The values for fossil Melanopsis from GBY vary along stratigraphy; they are highest around 0.70710 in Cycles 1 and 2, decrease to around 0.70685 in Cycle 3, and exhibit upward trending fluctuations in the subsequent cycles to 0.70703 in Cycle 6. This trend reveals the dominance of the Hermon Jurassic aquifer during the earlier, colder periods before the Matuyama-Brunhes Boundary (MBB) and enhanced influence of the Golan basaltic aquifers, in subsequent warmer periods, indicating that the MBB coincides with climate warming as supported by other indicators. Hence, this global geochronological indicator of 0.78 Ma is also potentially a global palaeoclimatic marker. The similarity between the Sr isotope composition of the Jordan River waters and Melanopsis and those from Cycle 3 suggests that the current climate corresponds to that of the warmest period within the record of GBY, clarifying the comparative interpretation of this 100 k.yr. climate record. PMID- 21036386 TI - Human basophils express amphiregulin in response to T cell-derived IL-3. AB - BACKGROUND: Amphiregulin, a member of the epidermal growth factor family, is expressed by activated mouse T(H)2 cells. Amphiregulin produced by mouse hematopoietic cells contributes to the elimination of a nematode infection by a type 2 effector response. OBJECTIVE: To identify the human peripheral blood cell population expressing amphiregulin. METHODS: Amphiregulin-expressing cells were identified by flow cytometry of cell surface markers and histologic staining. Histamine and amphiregulin in supernatants were measured by enzyme immunoassay. Quantitative real-time PCR was used to measure mRNA expression. RESULTS: Stimulation of human PBMCs by anti-CD3 + anti-CD28 antibodies induced expression of amphiregulin mRNA and protein by a non-T-cell population. The amphiregulin producing cells were basophils, as judged by morphology and expression of CD203c and CD123 (IL-3 receptor alpha chain). Activated mouse basophils also produced amphiregulin. Amphiregulin expression by basophils in response to anti-TCR stimulation required IL-3 produced by T cells, and IL-3 alone induced high levels of amphiregulin expression by purified basophils. Amphiregulin was expressed at much higher levels when human basophils were stimulated by IL-3 than by IgE cross linking, whereas the opposite was true for IL-4 expression and histamine release. Heparin-binding epidermal growth factor-like growth factor was also expressed by IL-3-stimulated human basophils. PBMCs from human subjects with asthma contained significantly higher numbers of basophils able to produce amphiregulin compared with controls with or without allergy. CONCLUSION: IL-3 can induce basophils to express high levels of amphiregulin, which may contribute to tissue remodeling during type 2 immune responses such as asthma. PMID- 21036387 TI - Point mutants of forkhead box P3 that cause immune dysregulation, polyendocrinopathy, enteropathy, X-linked have diverse abilities to reprogram T cells into regulatory T cells. AB - BACKGROUND: Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) is a primary immunodeficiency with autoimmunity caused by mutations in forkhead box P3 (FOXP3), which encodes a transcription factor involved in regulatory T (Treg) cell function. The mechanistic basis for how different mutations in FOXP3 cause distinct manifestations of IPEX remains unclear. OBJECTIVE: To determine whether 3 different point mutants of FOXP3 that cause severe or mild IPEX differ in their ability to reprogram conventional T cells into Treg cells. METHODS: Human CD4(+) T cells were transduced with wild-type or point mutant forms of FOXP3, and changes in cell surface marker expression, cytokine production, proliferation and suppressive capacity were assessed. Ex vivo T(H)17 cells were also transduced with different forms of FOXP3 to monitor changes in IL-17 production. RESULTS: The forkhead mutant F373A failed to upregulate CD25 and CCR4, did not suppress cytokine production, and induced suppressive activity less effectively than wild-type FOXP3. In contrast, although the forkhead mutant R347H was also defective in upregulation of CD25, it suppressed the production of cytokines, conferred suppressive capacity on CD4(+) T cells, and suppressed IL-17 production. F324L, a mutant outside the forkhead domain associated with mild IPEX, was equivalent to wild-type FOXP3 in all aspects tested. CONCLUSION: Mutations in FOXP3 that cause IPEX do not uniformly abrogate the ability of FOXP3 to regulate transcription and drive the development of Treg cells. These data support the notion that factors in addition to functional changes in Treg cells, such as alterations in conventional T cells, are involved in the pathogenesis of IPEX. PMID- 21036389 TI - A place for nouns and a place for verbs? A critical review of neurocognitive data on grammatical-class effects. AB - It is generally held that noun processing is specifically sub-served by temporal areas, while the neural underpinnings of verb processing are located in the frontal lobe. However, this view is now challenged by a significant body of evidence accumulated over the years. Moreover, the results obtained so far on the neural implementation of noun and verb processing appear to be quite inconsistent. The present review briefly describes and critically re-considers the anatomo-correlative, neuroimaging, MEG, TMS and cortical stimulation studies on nouns and verbs with the aim of assessing the consistency of their results, particularly within techniques. The paper also addresses the question as to whether the inconsistency of the data could be due to the variety of the tasks used. However, it emerged that neither the different investigation techniques used nor the different cognitive tasks employed fully explain the variability of the data. In the final section we thus suggest that the main reason for the emergence of inconsistent data in this field is that the cerebral circuits underlying noun and verb processing are not spatially segregated, at least for the spatial resolution currently used in most neuroimaging studies. PMID- 21036388 TI - Effect of filaggrin breakdown products on growth of and protein expression by Staphylococcus aureus. AB - BACKGROUND: Colonization of the skin by Staphylococcus aureus in individuals with atopic dermatitis exacerbates inflammation. Atopic dermatitis is associated with loss-of-function mutations in the filaggrin (FLG) gene, accompanied by reduced levels of filaggrin breakdown products on the skin. OBJECTIVE: To assess the affect of growth in the presence of the filaggrin breakdown products urocanic acid (UCA) and pyrrolidone carboxylic acid (PCA) on fitness of and protein expression by S aureus. METHODS: S aureus was grown for 24 hours in the presence of UCA and PCA, and the density of the cultures was monitored by recording OD(600) values. Cell wall extracts and secreted proteins of S aureus were isolated and analyzed by SDS-PAGE. Cell wall-associated proteins known to be involved in colonization and immune evasion including clumping factor B, fibronectin binding proteins, protein A, iron-regulated surface determinant A, and the serine-aspartate repeat proteins were examined by Western immunoblotting. RESULTS: Acidification of growth media caused by the presence of UCA and PCA resulted in reduced growth rates and reduced final cell density of S aureus. At the lower pH, reduced expression of secreted and cell wall-associated proteins, including proteins involved in colonization (clumping factor B, fibronectin binding protein A) and immune evasion (protein A), was observed. Decreased expression of iron-regulated surface determinant A due to growth with filaggrin breakdown products appeared to be independent of the decreased pH. CONCLUSION: S aureus grown under mildly acidic conditions such as those observed on healthy skin expresses reduced levels of proteins that are known to be involved in immune evasion. PMID- 21036390 TI - Educational aspiration-expectation discrepancies: relation to socioeconomic and academic risk-related factors. AB - This study examines whether disconnection between educational aspirations and expectations is associated with socioeconomic status, academic performance, academic risk-related behaviors and related psychosocial factors in an ethnically and economically diverse sample of early adolescents from a public middle school (N = 761). Results suggest that students who aspire to achieve more than they expect to achieve also are likely to have more economically disadvantaged backgrounds and poorer academic performance. These students also show a variety of academic and social risks. Specifically, students whose aspirations exceeded their expectations reported lower levels of school bonding, higher levels of test/performance anxiety, and elevated behavioral/emotional difficulties. Results are discussed in terms of social-cognitive theory as well as applications for promoting student social and academic success. PMID- 21036391 TI - Ranking of drugs: a more balanced risk-assessment. PMID- 21036392 TI - Aerosol drug delivery: developments in device design and clinical use. AB - Aerosolised drugs are prescribed for use in a range of inhaler devices and systems. Delivering drugs by inhalation requires a formulation that can be successfully aerosolised and a delivery system that produces a useful aerosol of the drug; the particles or droplets need to be of sufficient size and mass to be carried to the distal lung or deposited on proximal airways to give rise to a therapeutic effect. Patients and caregivers must use and maintain these aerosol drug delivery devices correctly. In recent years, several technical innovations have led to aerosol drug delivery devices with efficient drug delivery and with novel features that take into account factors such as dose tracking, portability, materials of manufacture, breath actuation, the interface with the patient, combination therapies, and systemic delivery. These changes have improved performance in all four categories of devices: metered dose inhalers, spacers and holding chambers, dry powder inhalers, and nebulisers. Additionally, several therapies usually given by injection are now prescribed as aerosols for use in a range of drug delivery devices. In this Review, we discuss recent developments in the design and clinical use of aerosol devices over the past 10-15 years with an emphasis on the treatment of respiratory disorders. PMID- 21036393 TI - Drug harms in the UK: a multicriteria decision analysis. AB - BACKGROUND: Proper assessment of the harms caused by the misuse of drugs can inform policy makers in health, policing, and social care. We aimed to apply multicriteria decision analysis (MCDA) modelling to a range of drug harms in the UK. METHODS: Members of the Independent Scientific Committee on Drugs, including two invited specialists, met in a 1-day interactive workshop to score 20 drugs on 16 criteria: nine related to the harms that a drug produces in the individual and seven to the harms to others. Drugs were scored out of 100 points, and the criteria were weighted to indicate their relative importance. FINDINGS: MCDA modelling showed that heroin, crack cocaine, and metamfetamine were the most harmful drugs to individuals (part scores 34, 37, and 32, respectively), whereas alcohol, heroin, and crack cocaine were the most harmful to others (46, 21, and 17, respectively). Overall, alcohol was the most harmful drug (overall harm score 72), with heroin (55) and crack cocaine (54) in second and third places. INTERPRETATION: These findings lend support to previous work assessing drug harms, and show how the improved scoring and weighting approach of MCDA increases the differentiation between the most and least harmful drugs. However, the findings correlate poorly with present UK drug classification, which is not based simply on considerations of harm. FUNDING: Centre for Crime and Justice Studies (UK). PMID- 21036394 TI - Transferrin receptor gene and protein expression and localization in human IUGR and normal term placentas. AB - Iron (Fe) deficiency in pregnancy is associated to low birth weight and premature delivery while in adults it can result in increased blood pressure and cardiovascular disease. Cellular Fe uptake is mediated by the Transferrin Receptor 1 (TFRC), located in the trophoblast membranes. Here, we measured TFRC mRNA expression (Real Time PCR) and TFRC protein expression and localization (Western Blotting and immunohistochemistry) in IUGR compared to control placentas. A total of 50 IUGR and 56 control placentas were studied at the time of elective cesarean section. IUGR was defined by ultrasound in utero, and confirmed by birth weight <10th percentile. Three different severity groups were identified depending on the umbilical artery pulsatility index and fetal heart rate. TFRC mRNA expression was significantly lower in IUGR placentas compared to controls (p < 0.05), and this was confirmed for TFRC protein levels. In both experiments the most severe IUGR group presented lower expression compared to the other groups, and this was also related to umbilical venous oxygen levels. TFRC protein localization in the villous trophoblast did not differ in the groups, and was predominantly present in the syncytiotrophoblast. In conclusion, these are the first observations about TFRC expression in human IUGR placentas, demonstrating its significant decrease in IUGR vs controls. Thus, Fe transport could be limited in IUGR placentas. Further studies are needed to study components of the placental Fe transport system and to clarify the regulation mechanisms involved in TFRC expression, possibly altered in IUGR placentas. PMID- 21036395 TI - Placenta weight percentile curves for singleton and twins deliveries. AB - OBJECTIVE: To establish updated placental percentile nomograms in a large North American population for singleton and twin gestations for the use of researchers and clinicians. STUDY DESIGN: Data was extracted from our computerized registry; McGill Obstetrics and Neonatal Database (MOND). The registry includes all the obstetrical data on all deliveries at the McGill University, including placental weight, placental pathologies, maternal and perinatal complications. 20,635 singleton deliveries and 527 twin deliveries were included. Placental weight, gestational age at delivery, birth weight and gender were retrieved. Tables and figures for the 3rd,10th,25th, 50th, 75th 90th, and 97th percentile of placental weight by gestational age, placental weight by birth weight and placental to birth weight ratio by gestational age were produced. RESULTS: Tables and figures are presented for placental percentiles curves according to gestational age, gestational weight and gender for singleton and twin deliveries. In addition, tables and figures are presented for the ratio of placental weight to birth weight. CONCLUSIONS: Population percentile curves have been produced for placental weight and for the ratio of placental weight to birth weight to for singleton and twin deliveries. PMID- 21036396 TI - Effect of alpha-melanocyte stimulating hormone on locomotor recovery following spinal cord injury in mice: Role of serotonergic system. AB - The present study underscores the effect of serotonergic antagonist on alpha melanocyte stimulating hormone (alpha-MSH) induced neuronal regeneration. Swiss albino mice were subjected to experimental spinal cord injury (ESCI) and treated with serotonergic antagonist, ritanserin, alone or in combination with alpha-MSH, and the locomotor recovery was investigated. ESCI was induced at thoracic T(10 12) level by compression method. Motor function score (0-10) of each mouse was monitored prior to, and on days 1, 4, 7, 10 and 14 following ESCI. Untreated ESCI animals showed almost normal hind limb motor function by 14days. Similar degree of recovery was observed on day 10 in animals given alpha-MSH or ritanserin. However, in animals treated with both agents, comparable recovery was observed on day 4. While histological examination of the spinal cord following ESCI showed demyelination, necrosis and cyst formation, treatment with ritanserin, alone and in combination with alpha-MSH, significantly prevented the tissue damage. We suggest that early antagonism of serotonergic 5-HT(2a/2c) receptors may potentiate the neurotropic and locomotor recovery activity of alpha-MSH. PMID- 21036397 TI - Aplastic anemia & MDS International Foundation (AA&MDSIF): Bone Marrow Failure Disease Scientific Symposium 2010. AB - Aplastic anemia (AA) and myelodysplastic syndromes (MDS) are a heterogeneous group of rare hematological disorders belonging to the Bone Marrow Failure (BMF) syndromes. The Aplastic Anemia and Myelodysplastic Syndromes International Foundation (AA&MDSIF) is a non-profit organization dedicated to supporting patients and families living with a BMF disease. They work to bring investigators together in a collaborative manner. This article summarizes key presentations from the last AA&MDSIF scientific symposium held in Bethesda, Maryland on March 2010. PMID- 21036398 TI - Commercial formulation containing quinclorac and metsulfuron-methyl herbicides inhibit acetylcholinesterase and induce biochemical alterations in tissues of Leporinus obtusidens. AB - The effects of commercial formulation containing quinclorac and metsulfuron methyl herbicides on acetylcholinesterase (AChE), antioxidant profile and metabolic parameters in teleost fish (Leporinus obtusidens) were studied. The fish were exposed during 90 days to commercial formulation containing quinclorac (204 MUg L(-1)) and metsulfuron-methyl (5.8 MUg L(-1)) herbicides in rice field irrigated condition. AChE activity in the brain and muscle decreased after exposure to both commercial formulations. The same response was observed for the TBARS levels in brain, liver and muscle. Liver catalase activity reduced after exposure to commercial formulation containing quinclorac and metsulfuron-methyl herbicides. Metabolic parameters in the liver and white muscle (glycogen, lactate, protein and glucose) were determined. These parameters showed different changes after exposure to both commercial formulations. This study pointed out long-term effects of exposure to commercial formulations containing herbicides used in rice on metabolic and enzymatic parameters in tissues of L. obtusidens. PMID- 21036399 TI - Clinical and programmatic costs of implementing colorectal cancer screening: evaluation of five programs. AB - BACKGROUND: The Centers for Disease Control and Prevention (CDC) initiated the Colorectal Cancer Screening Demonstration Program (CRCSDP) in 2005 to explore the feasibility of establishing a colorectal cancer screening program for underserved US populations. We provide a detailed overview of the evaluation and an assessment of the costs incurred during the service delivery (screening) phase of the program. METHODS: Tailored cost questionnaires were completed by staff at the five CRCSDP sites for the first 2 years of the program. We collected cost data for clinical and programmatic activities (program management, data collection and tracking, etc.). We also measured in-kind contributions and assigned values to them. RESULTS: During the first 2 years of the demonstration excluding the start up cost, the average cost per person was $2569. Per person cost of clinical services alone ranged from $264 to $1385, while per person programmatic costs ranged from $545 to $3017. CONCLUSION: Colorectal cancer screening programs can incur substantial costs for some non-clinical activities, such as data collection/tracking, and these support activities should be managed carefully to control costs and ensure successful program implementation. Our findings highlight the importance of performing economic evaluation to guide the design of future colorectal cancer screening programs. PMID- 21036400 TI - Genetic screening for OPA1 and OPA3 mutations in patients with suspected inherited optic neuropathies. AB - PURPOSE: Autosomal-dominant optic atrophy (DOA) is one of the most common inherited optic neuropathies, and it is genetically heterogeneous, with mutations in both OPA1 and OPA3 known to cause disease. Approximately 60% of cases harbor OPA1 mutations, whereas OPA3 mutations have been reported in only 2 pedigrees with DOA and premature cataracts. The aim of this study was to determine the yield of OPA1 and OPA3 screening in a cohort of presumed DOA cases referred to a tertiary diagnostic laboratory. DESIGN: Retrospective case series. PARTICIPANTS: One hundred eighty-eight probands with bilateral optic atrophy referred for molecular genetic investigations at a tertiary diagnostic facility: 38 patients with an autosomal-dominant pattern of inheritance and 150 sporadic cases. METHODS: OPA1 and OPA3 genetic testing was initially performed using polymerase chain reaction-based sequencing methods. The presence of large-scale OPA1 and OPA3 genomic rearrangements was assessed further with a targeted comparative genomic hybridization microarray platform. The 3 primary Leber hereditary optic neuropathy (LHON) mutations, m.3460G->>A, m.11778G->A, and m.14484T->C, also were screened in all patients. MAIN OUTCOME MEASURES: The proportion of patients with OPA1 and OPA3 pathogenic mutations. The clinical profile observed in molecularly confirmed DOA cases. RESULTS: Twenty-one different OPA1 mutations were found in 27 (14.4%) of the 188 probands screened. The mutations included 6 novel pathogenic variants and the first reported OPA1 initiation codon mutation at c.1A >T. An OPA1 missense mutation, c.239A->G (p.Y80C), was identified in an 11-year old black girl with optic atrophy and peripheral sensorimotor neuropathy in her lower limbs. The OPA1 detection rate was significantly higher among individuals with a positive family history of visual failure (50.0%) compared with sporadic cases (5.3%). The primary LHON screen was negative in the patient cohort, and additional molecular investigations did not reveal any large-scale OPA1 rearrangements or OPA3 genetic defects. The mean baseline visual acuity for the OPA1-positive group was 0.48 logarithm of the minimum angle of resolution (units mean Snellen equivalent, 20/61; range, 20/20-20/400; 95% confidence interval, 20/52-20/71), and visual deterioration occurred in 54.2% of patients during follow-up. CONCLUSIONS: OPA1 mutations are the most common genetic defects identified in patients with suspected DOA, whereas OPA3 mutations are very rare in isolated optic atrophy cases. PMID- 21036401 TI - Inexpensive video cameras used by parents to record social communication in epidemiological investigations in early childhood-A feasibility study. AB - We tested the feasibility of parents recording social interactions with their infants using inexpensive camcorders, as a potential method of effective, convenient, and economical large scale data gathering on social communication. Participants were asked to record two short video clips during either play or a mealtime, and return the data. Sixty-five video clips (32 pairs) were returned by 33 families, comprising 8.5% of families contacted, 44.6% of respondents and 51.6% of those sent a camcorder, and the general visual and sound quality of the data was assessed. Audio and video quality were adequate for analysis in 85% of clips and several social behaviours, including social engagement and contingent responsiveness, could be assessed in 97% of clips. We examined two quantifiable social behaviours quantitatively in both adults and infants: gaze direction and duration, and vocalization occurrence and duration. It proved difficult for most observers to obtain a simultaneous clear view of the parents and infant's face. Video clips obtained by parents are informative and usable for analysis. Further work is required to establish the acceptability of this technique in longitudinal studies of child development and to maximize the return of usable data. PMID- 21036402 TI - Anticipatory reaching of seven- to eleven-month-old infants in occlusion situations. AB - The present study examined 7- to 11-month-old infants' anticipatory and reactive reaching for temporarily occluded objects. Infants were presented with laterally approaching objects that moved at different velocities (10, 20, and 40 cm/s) in different occlusion situations (no-, 20 cm-, and 40 cm-occlusion), resulting in occlusion durations ranging between 0 and 4s. Results show that except for object velocity and occlusion distance, occlusion duration was a critical constraint for infants' reaching behaviors. We found that the older infants reached more often, but that an increase in occlusion duration resulted in a decline in reaching frequency that was similar across age groups. Anticipatory reaching declined with increasing occlusion duration, but the adverse effects for longer occlusion durations diminished with age. It is concluded that with increasing age infants are able to retain and use information to guide reaching movements over longer periods of non-visibility, providing support for the graded representation hypothesis (Jonsson & von Hofsten, 2003) and the two-visual systems model (Milner & Goodale, 1995). PMID- 21036403 TI - Posttraumatic stress disorder and psychiatric co-morbidity following stroke: the role of alexithymia. AB - More research is needed to further our understanding of posttraumatic stress disorder symptoms (PTSD) and psychiatric co-morbidity following stroke, especially the trajectories of such symptoms over time. Previous studies suggest that exposure to a traumatic experience such as stroke is not sufficient to explain the etiology of PTSD. Alexithymia may be involved, but its relationships with PTSD and psychiatric co-morbidity following stroke remains unclear. This study aims to address these knowledge gaps. While in hospital, stroke patients (n=90) completed questionnaires assessing PTSD symptoms, psychiatric co morbidity, alexithymia and physical disability. PTSD symptoms and psychiatric co morbidity were re-assessed approximately 3 months post-stroke (n=78). The severity of post-stroke PTSD did not change significantly over time, while psychiatric co-morbidity reduced significantly. Alexithymia, in particular difficulty in identifying feelings, was associated with severity of post-stroke PTSD and psychiatric co-morbidity at baseline, but after adjusting for these, there was no significance 3 months post-stroke. We suggest that patients' difficulty in identifying feelings had a role to play in influencing relatively short-term rather than long-term PTSD and co-morbid psychiatric symptoms. Alternatively, PTSD could be interpreted as driving the alexithymic characteristics. PMID- 21036404 TI - Methods for transcriptomic analyses of the porcine host immune response: application to Salmonella infection using microarrays. AB - Technological developments in both the collection and analysis of molecular genetic data over the past few years have provided new opportunities for an improved understanding of the global response to pathogen exposure. Such developments are particularly dramatic for scientists studying the pig, where tools to measure the expression of tens of thousands of transcripts, as well as unprecedented data on the porcine genome sequence, have combined to expand our abilities to elucidate the porcine immune system. In this review, we describe these recent developments in the context of our work using primarily microarrays to explore gene expression changes during infection of pigs by Salmonella. Thus while the focus is not a comprehensive review of all possible approaches, we provide links and information on both the tools we use as well as alternatives commonly available for transcriptomic data collection and analysis of porcine immune responses. Through this review, we expect readers will gain an appreciation for the necessary steps to plan, conduct, analyze and interpret the data from transcriptomic analyses directly applicable to their research interests. PMID- 21036405 TI - Cutting edge technologies in animalomics. PMID- 21036406 TI - The effects of methylprednisolone, montelukast and indomethacine in experimental otitis media with effusion. AB - OBJECTIVES: The present study aimed to investigate the effects of indomethacine, montelukast and methylprednisolone in management of experimental otitis media with effusion. METHODS: Forty Wistar albino rats of which the weights ranged between 310 and 370 g were included in this study. Middle ear effusion was created by transtympanic histamine injection. The presence of effusion was confirmed by otomicroscopic examination. Thirty-seven rats with effusion were divided into 4 groups (methylprednisolone, montelukast, indomethacine and saline control groups). All agents were administered for a period of consecutive 10 days. At the 11th days of administration, the recovery of effusion was confirmed by otomicroscopic examination. Tympanic bullae of the rats were removed and histopathological examinations were carried out. In the histopathological examination, the neutrophil leukocytes accumulated in the middle ear submucosa were counted. RESULTS: The mean numbers of submucosal neutrophils in the methylprednisolone, montelukast, indomethacine, and saline groups were 24.6+/ 8.1, 54.1+/-6.2, 52.3+/-7.3, 55.7+/-8.3, respectively. The otomicroscopic recovery rates of effusion in the methylprednisolone, montelukast, indomethacine, and saline groups were 18/18 (100%), 8/18 (44%), 2/14 (14%), 2/18 (11%) respectively. CONCLUSIONS: Methylprednisolone and montelukast ameliorate the middle ear effusion. However, only methylprednisolone reduces the submucosal infiltration of the neutrophil leukocytes which are the most evident cell of inflammatory process. Montelukast is effective in the resolution of experimental otitis media with effusion. PMID- 21036407 TI - Tributyltin-induced imposex in marine gastropods involves tissue-specific modulation of the retinoid X receptor. AB - Despite the large number of studies on the phenomenon of imposex, the mechanism underlying the abnormal growth of male sexual characters onto females in numerous gastropod species is yet to be fully elucidated. Although several hypotheses have been raised over the years, a convincing body of evidence indicates that tributyltin-induced imposex involves the abnormal modulation of the retinoid X receptor (RXR). Here, we investigate the RXR gene transcription at different timings and tissues upon exposure to environmentally relevant concentrations of tributyltin (TBT) (100 ng Sn/L TBT) in both genders of the imposex susceptible gastropod Nucella lapillus. RXR gene transcription was determined at two time points (i.e., before and after imposex initiation) by quantitative Real Time PCR in potential target tissues: the central nervous system (CNS), penis/penis forming area (PFA), gonads and digestive gland. TBT-exposure altered transcription of RXR gene in a tissue and sex specific manner. In the CNS, a significant down-regulation was observed in females both before and after imposex initiation (P<=0.01 and P<=0.05, respectively). A similar trend was observed in male CNS at the first time-point, although differences between control and the TBT-exposed group were just above significance (P=0.059). The penis/PFA showed no differences in transcription of RXR gene between control and TBT exposed female snails before imposex induction, or before and after imposex initiation for males. However, male penis showed higher transcription of RXR gene in comparison to the PFA of females. After imposex has been induced, a significant (P<=0.001) increase in transcription of RXR gene was observed in penis of females with vas deference sequence index (VDS) levels of 3-4 in comparison with the PFA of both control and imposex females with VDS 1-2. At advanced stages of imposex, females displayed RXR transcription patterns in penis identical to those of males, which points to a functional role of RXR in the penis of both genders. In the other tissues, gonads and digestive gland, RXR gene transcription was not affected by TBT, at any of the analysed time-points. These patterns of RXR gene transcription upon TBT exposure highlight the pivotal involvement of the CNS in the mechanism of imposex induction. We integrate the results in a conceptual model, and discuss the central role of RXR and the retinoic acid signalling pathways in imposex and male genitalia formation in gastropods. PMID- 21036408 TI - Evaluation of multi-dimensional outcomes of chronic diseases: a clinical example from China. AB - The purpose of this study is to provide the evidence of individualized/personalized care by evaluating multi-dimensional outcomes of chronic diseases in the elderly. We used primary osteoporosis as an example, to evaluate the outcomes of three treatments (calcium combined vitamin D=Ca+vit.D; estrogen and disphosphonates) at the same time with biological dimension (bone mineral density=BMD) and socio-psychological dimension (health-related quality of life=HR-QOL), using the medical outcomes study short-form 36-item health survey (SF-36) and cost dimension (drug cost). Using BMD as the outcome index, disphosphonate was the most effective treatment, in terms of HR-QOL, estrogen was the most effective while Ca+vit.D was the cheapest treatment, namely, different dimensional outcomes with different results. Outcome evaluation of chronic diseases in the elderly needs to combine psychological and socio-economic parameters together with the physiological measurement, to encourage a transition from "the disease-centered" to "the patient-centered" perspective as well as achieve sustainable and coordinated development of health and socio-economic resources. PMID- 21036409 TI - Angiotensin receptor blockers for prevention of new-onset type 2 diabetes: a meta analysis of 59,862 patients. AB - BACKGROUND: Angiotensin receptor blockers (ARBs) have been linked to reduced risk of new-onset diabetes, but the evidence was insufficient. OBJECTIVE AND METHODS: The aim of this study was to evaluate the effect of ARBs on the development of new-onset type 2 diabetes. Randomized controlled trials (RCTs) about ARBs and new onset diabetes were identified by electronic and manual searches. RESULTS: Eleven RCTs with 79,773 patients (59,862 non-diabetic patients at baseline) were included in this study. Compared with control group, incidence of new-onset diabetes was significantly reduced in ARBs group [OR 0.79, (0.74, 0.84)] and various categories of ARBs subgroup. ARBs were associated with significant reduction in the risk of new-onset diabetes compared with placebo [OR 0.83, (0.78, 0.89)], beta-blocker [OR 0.73, (0.62, 0.87)], calcium channel blocker [OR 0.76, (0.68, 0.85)] and non-ARB [OR 0.57, (0.36, 0.91)]. ARBs were associated with significant reduction in the risk of new-onset diabetes in patients with hypertension [OR 0.74, (0.68, 0.81)], heart failure [OR 0.70, (0.50, 0.96)], impaired glucose tolerance [OR 0.85, (0.78, 0.92)] or cardiocerebrovascular diseases [OR 0.84, (0.72, 0.97)]. Compared with control group, incidence of new onset diabetes was significantly reduced in ARBs group, irrespective of achieved blood pressure level. ARBs were associated with a lower incidence of new-onset diabetes in Western population [OR 0.81, (0.76, 0.85)] and Japanese population [OR 0.61, (0.48, 0.79)]. CONCLUSION: There is sufficient evidence that ARBs have beneficial effect in preventing new-onset type 2 diabetes. ARBs should be considered in patients with high risk of developing diabetes. PMID- 21036410 TI - Assessment and quantification of post-weaning multi-systemic wasting syndrome severity at farm level. AB - Post-weaning multi-systemic wasting syndrome (PMWS) causes major economic losses for the English pig industry and severity of clinical signs and economic impact vary considerably between affected farms. We present here a novel approach to quantify severity of PMWS based on morbidity and mortality data and presence of porcine circovirus type 2 (PCV2). In 2008-2009, 147 pig farms across England, non vaccinating for PCV2, were enrolled in a cross-sectional study. Factor analysis was used to generate variables representing biologically meaningful aspects of variation among qualitative and quantitative morbidity variables. Together with other known variables linked to PMWS, the resulting factors were included in a principal component analysis (PCA) to derive an algorithm for PMWS severity. Factor analysis resulted in two factors: Morbidity Factor 1 (MF1) representing mainly weaner and grower morbidity, and Morbidity Factor 2 (MF2) which mainly reflects variation in finisher morbidity. This indicates that farms either had high morbidity mainly in weaners/growers or mainly in finishers. Subsequent PCA resulted in the extraction of one component representing variation in MF1, post weaning mortality and percentage of PCV2 PCR positive animals. Component scores were normalised to a value range from 0 to 10 and farms classified into: non or slightly affected farms with a score <4, moderately affected farms with scores 4 6.5 and highly affected farms with a score >6.5. The identified farm level PMWS severities will be used to identify risk factors related to these, to assess the efficacy of PCV2 vaccination and investigating the economic impact of potential control measures. PMID- 21036411 TI - Dose-response modeling of Salmonella using outbreak data. AB - Salmonella is a key human pathogen worldwide, most often associated with food poisoning incidences. There is a small number of predominant serotypes found in human cases. The role of exposure in the epidemiology of Salmonella can be explained using dose-response assessment both for infection and acute enteric illness. Dose-response studies are traditionally based on human challenge experiments but an alternative is to use outbreak data. Such data were collected from the published literature which included estimates of the dose ingested and the attack rate. Separate dose-response models for infection and illness given infection were fitted using a multi-level statistical framework. These models incorporated serotype and susceptibility as categorical covariates, and adjusted for heterogeneity in exposure. The results indicate that both the risk of infection and the risk of illness given infection increase with dose. The dose response model incorporating data from all outbreaks had an infection ID50 of 7 CFU's and illness ID50 of 36 CFUs. This is indicative of much higher infectivity and pathogenicity compared with feeding studies of healthy human volunteers with laboratory adapted strains. No differences were found in the outbreak models between serotypes and susceptibility categories. However, for serotypes other than S. Enteritidis or S. Typhimurium, results indicate that a minor proportion of individuals exposed will not fall ill even at high doses. The dose-response relations indicate that outbreaks are associated with higher doses making it more likely to have a higher attack rate. Applications of the dose-response model in outbreak situations where either dose or attack rate is missing were successfully used to clarify the epidemiology. Finally, the dose-response models described here can be readily used in quantitative microbiological risk assessment to predict human infection and illness rates. A simple Excel spreadsheet implementing the model has been prepared and is available from the authors. PMID- 21036412 TI - Selection, application and monitoring of Lactobacillus paracasei strains as adjunct cultures in the production of Gouda-type cheeses. AB - Raw milk cheeses have more intense flavours than cheeses made from pasteurized milk and harbour strains with potential adjunct properties. Two Lactobacillus paracasei strains, R-40926 and R-40937, were selected as potential adjunct cultures from a total of 734 isolates from good quality artisan raw milk Gouda type cheeses on the basis of their prevalence in different cheese types and/or over several production batches, safety and technological parameters. Conventional culturing, isolation and identification and a combined PCR-DGGE approach using total cheese DNA extracts and DNA extracts obtained from culturable fractions were employed to monitor viability of the introduced adjuncts and their effect on the cheese microbiota. The control cheese made without adjuncts was dominated by members of the starter, i.e. Lactococcus lactis and Leuconostoc pseudomesenteroides. In the cheeses containing either R-40926 or R-40937, the respective adjuncts increased in number as ripening progressed indicating that both strains are well adapted to the cheese environment and can survive in a competitive environment in the presence of a commercial starter culture. Principal component analysis of cheese volatiles determined by steam distillation-extraction and gas chromatography-mass spectrometry could differentiate cheeses made with different concentrations of adjunct R-40926 from the control cheese, and these differences could be correlated to the proteolytic and lipolytic properties of this strain. Collectively, results from microbiological and metabolic analyses indicate that the screening procedure followed throughout this study was successful in delivering potential adjunct candidates to enrich or extend the flavour palette of artisan Gouda-type cheeses under more controlled conditions. PMID- 21036413 TI - Determination of viable wine yeast using DNA binding dyes and quantitative PCR. AB - The detection and quantification of wine yeast can be misleading due to under or overestimation of these microorganisms. Underestimation may be caused by variable growing rates of different microorganisms in culture media or the presence of viable but non-cultivable microorganisms. Overestimation may be caused by the lack of discrimination between live and dead microorganisms if quantitative PCR is used to quantify with DNA as the template. However, culture-independent methods that use dyes have been described to remove the DNA from dead cells and then quantify the live microorganisms. Two dyes have been studied in this paper: ethidium monoazide bromide (EMA) and propidium monoazide bromide (PMA). The technique was applied to grape must fermentation and ageing wines. Both dyes presented similar results on yeast monitoring. Membrane cell recovery was necessary when yeasts were originated from ethanol-containing media. When applied to grape must fermentation, differences of up to 1 log unit were seen between the QPCR estimation with or without the dye during the stationary phase. In ageing wines, good agreement was found between plating techniques and QPCR. Most of the viable cells were also culturable and no differences were observed with the methods, except for Zygosaccharomyces bailii and Dekkera bruxellensis where much higher counts were occasionally detected by QPCR. The presence of excess dead cells did not interfere with the quantification of live cells with either of the dyes. PMID- 21036414 TI - Increased variation of the response index of nociception during noxious stimulation in patients during general anaesthesia. AB - OBJECTIVE: Analgesia is an important part of general anaesthesia, but no direct indicators of nociceptive-anti-nociceptive balance have been validated in detail. The Response Index of Nociception (RN) is a multiparameter approach which combines photoplethysmographic waveform (PPG), State Entropy (SE), Response Entropy (RE), and heart rate variability (HRV). We aimed at evaluating RN during general anaesthesia; especially we wanted to compare pre- and post-index values of certain noxious stimuli to the average index values. Our assumption was that RN could be a useful indicator of nociceptive-anti-nociceptive balance during the surgery. METHODS: Sixty women undergoing gynaecological or breast surgery participated in the study. All patients had elective surgery and anaesthesia was maintained with propofol-remifentanil target controlled infusion. Neuromuscular blocking agent rocuronium was used at the beginning of the surgery. Electrocardiography (ECG), photoplethysmography (PPG) and electroencelophalography (EEG) were registered and extracted off-line. An index, reflecting amplitude and frequency of occurrence of abrupt increases ("peaks") in the RN was evaluated during surgery in general and around occurrences of predefined noxious stimuli in particular. RESULTS: Fifty-four patients were eligible for analysis. Patient movement was associated with increased index values, both before and after the event. Post-event values of the index for intubation and skin incision were higher than its intra-surgery baseline, while pre-event values remained unchanged. CONCLUSION: Changes in RN can be used to detect noxious stimuli during surgery. RN also predicted movement in our patients under propofol-remifentanil anaesthesia. PMID- 21036415 TI - Frequent ALK rearrangement and TTF-1/p63 co-expression in lung adenocarcinoma with signet-ring cell component. AB - Primary adenocarcinoma with signet-ring cell component (Ad-SRCC) of the lung has been well characterized clinicopathologically and histologically, but their genetics has rarely been investigated. A recent report suggesting an association between Ad-SRCC and EML4-ALK fusion prompted us to undertake a histological, immunohistochemical, and molecular analysis of 10 cases of primary Ad-SRCC identified out of 699 lung adenocarcinomas (1.4%). Most of the Ad-SRCCs showed characteristic architectural as well as cytological features including cohesive clustering of signet-ring cells, a solid/acinar growth pattern, and alveolar filling at the tumor periphery. Diffuse co-expression of TTF-1 and p63 was observed in half of the Ad-SRCCs, and this immunoprofile has not been recognized previously. Four Ad-SRCCs (40%) harbored ALK translocations detected by reverse transcriptase polymerase chain reaction, fluorescence in situ hybridization, and immunohistochemistry. One new EML4-ALK fusion variant was identified. One ALK rearranged tumor showed focal squamous differentiation. None of the present Ad SRCCs had EGFR or KRAS mutations, regardless of ALK status. This study successfully utilized tumor histology alone to identify a subset of adenocarcinomas showing a high rate of ALK translocation. The characteristic histology, immunoprofile, frequent ALK translocation, and total lack of EGFR or KRAS mutations, may suggest that Ad-SRCC forms a histologically/molecularly coherent subgroup of adenocarcinoma. PMID- 21036416 TI - Correlation of USMLE Step 1 scores with performance on dermatology in-training examinations. AB - BACKGROUND: Although United States Medical Licensing Examination (USMLE) Step 1 was not designed to predict resident performance, scores are used to compare residency applicants. Multiple studies have displayed a significant correlation among Step 1 scores, in-training examination (ITE) scores, and board passage, although no such studies have been performed in dermatology. OBJECTIVE: The purpose of this study is to determine if this correlation exists in dermatology, and how much of the variability in ITE scores is a result of differences in Step 1 scores. This study also seeks to determine if it is appropriate to individualize expectations for resident ITE performance. METHODS: This project received institutional review board exemption. From 5 dermatology residency programs (86 residents), we collected Step 1 and ITE scores for each of the 3 years of dermatology residency, and recorded passage/failure on boards. Bivariate Pearson correlation analysis was used to assess correlation between USMLE and ITE scores. Ordinary least squares regression was computed to determine how much USMLE scores contribute to ITE variability. RESULTS: USMLE and ITE score correlations were highly significant (P < .001). Correlation coefficients with USMLE were: 0.467, 0.541, and 0.527 for ITE in years 1, 2, and 3, respectively. Variability in ITE scores caused by differences in USMLE scores were: ITE first year residency = 21.8%, ITE second-year residency = 29.3%, and ITE third-year residency = 27.8%. LIMITATIONS: This study had a relatively small sample size, with data from only 5 programs. CONCLUSIONS: There is a moderate correlation between USMLE and ITE scores, with USMLE scores explaining ~26% of the variability in ITE scores. PMID- 21036417 TI - The spectrum of hair loss in patients with mycosis fungoides and Sezary syndrome. AB - BACKGROUND: Alopecia can be a manifestation of mycosis fungoides (MF) and Sezary syndrome (SS), but the prevalence is unknown. OBJECTIVE: We sought to describe the clinicopathologic presentation and molecular features of alopecia in patients with MF/SS. METHODS: A retrospective chart review of a prospectively collected MF/SS database was used to identify patients with alopecia. The National Alopecia Areata Registry was used to identify patients with self-reported cutaneous T-cell lymphoma. RESULTS: Among 1550 patients with MF/SS, 38 patients with patchy, total scalp, or universal alopecia were identified. Thirteen of 38 (34%) had patchy alopecia clinically identical to alopecia areata. Scalp biopsy specimens were available in 5 of the 13 patients. Specimens from 4 patients had atypical T lymphocytes within the follicular epithelium or epidermis, and that from two patients had a histology of follicular mucinosis. The remaining 25 of 38 (66%) patients with MF/SS included 20 with alopecia within discreet patch/plaque or follicular lesions of MF and 5 with total-body hair loss, which presented only in those with generalized erythroderma and SS. LIMITATIONS: This was a retrospective study done at one cancer center. Biopsy specimens of alopecia were not available for every patient. CONCLUSIONS: Alopecia was observed in 2.5% of patients with MF/SS, with alopecia areata-like patchy loss in 34% and alopecia within MF lesions in 66%. PMID- 21036419 TI - Teledermatology for diagnosis and management of skin conditions: a systematic review. AB - OBJECTIVE: We performed a systematic review of the literature addressing teledermatology: (1) diagnostic accuracy/concordance; (2) management accuracy/concordance; (3) clinical outcomes; and (4) costs. METHODS: Peer reviewed controlled trials published in English between 1990 and 2009 were identified through MEDLINE and PubMed searches. RESULTS: Of 78 included studies, approximately two-thirds comparing teledermatology and clinic dermatology found better diagnostic accuracy with clinic dermatology. Diagnostic concordance of store and forward with clinic dermatology was good; concordance rates for live interactive and clinic dermatology were higher, but based on fewer patients. Overall rates of management accuracy were equivalent, but teledermatology and teledermatoscopy were inferior to clinic dermatology for malignant lesions. Management concordance was fair to excellent. There was insufficient evidence to evaluate clinical course outcomes. Patient satisfaction and preferences were comparable. Teledermatology reduced time to treatment and clinic visits and was cost-effective if certain assumptions were met. LIMITATIONS: Heterogeneity in studies (design, skin conditions, outcomes) limited the ability to pool data. CONCLUSION: The benefits of teledermatology need to be evaluated in the context of potential limitations. PMID- 21036418 TI - Quantification of gadolinium in fresh skin and serum samples from patients with nephrogenic systemic fibrosis. AB - BACKGROUND: Nephrogenic systemic fibrosis (NSF) is a rare, potentially fatal fibrosing disorder associated with renal insufficiency and gadolinium (Gd)-based contrast exposure. The cause remains unknown. To date, all efforts to investigate skin Gd concentrations in patients with NSF have been performed on paraffin embedded samples, and Gd deposition has not been correlated with disease activity by a statistically significant analysis. OBJECTIVE: We sought to: (1) quantify Gd concentration in fresh tissue skin biopsy specimens; (2) quantify and compare synchronous Gd concentration of affected skin and unaffected skin in patients with NSF (n = 13) with a control group (n = 13); and (3) quantify serum Gd. METHODS: We used inductively coupled plasma mass spectrometry. RESULTS: In patients with NSF, the mean ratio of paired Gd concentrations of affected skin to unaffected skin was 23.1, ranging from 1.2 to 88.9. Mean serum Gd concentrations in patients with NSF were 4.8 ng/mL, which is more than 10 times the level in control patients. A statistically significant correlation existed between serum and affected skin Gd concentrations (r(2) = .74, P < .0001). LIMITATIONS: Because of the feasibility of this study, the main limitation was the small sample size (n = 13 affected and 13 control). CONCLUSIONS: Determination of Gd concentrations in fresh skin samples and serum using inductively coupled plasma mass spectrometry demonstrates significant differences in the amounts of Gd in involved versus nonlesional skin of patients with NSF. This supports the role of differential free Gd deposition from Gd-based contrast in the pathogenesis of NSF. PMID- 21036420 TI - [Portable coagulometer devices in the monitoring and control of oral anticoagulation therapy: a systematic review]. AB - OBJECTIVE: To compare portable coagulometer devices and conventional coagulometers. The clinical validity will be estimated via anticoagulation control (maintenance of therapeutic range), patient satisfaction, thrombotic or haemorrhagic events and mortality. Analytical validity will be studied in quality control terms. DESIGN: Systematic review. DATA SOURCES: MEDLINE and EMBASE databases, CRD, Cochrane, EMEA, FDA, EuroScan and the ClinicalTrials.gov. METHODS: Inclusion criteria were studied in patients on anticoagulation therapy who used portable coagulometer devices. In an additional undertaking, the comparison with lab references was looked for, in order to evaluate the effectiveness. The quality of selected studies was assessed according to CASPe check-list. As meta-analysis was not possible, a qualitative synthesis was made. RESULTS: Four evaluation reports and 7 systematic reviews were selected (two of them with meta-analysis). After these, 22 original articles were included for this review and they had high or very high score for CASPe check-list (>=7/10). Almost all of the studies found very high correlations between portable coagulometer devices and conventional coagulometers (r>90), and clinical advantages such as lower incidence of thromboembolism events. Three systematic reviews showed a lower mortality index. CONCLUSIONS: The analytical-validity related articles show that portable coagulometers have an equivalent effectiveness to conventional coagulometers. Studies that include patient reported outcomes show that self-monitoring patients, by means of portable coagulometers, have better analytical measurement results and fewer rates of thromboembolic events. Survival was analysed in very few studies; nevertheless, all of these show lower mortality. Similarly, the minority of selected articles includes economic evaluations, although they suggest a better cost-effectiveness of portable coagulometers compared to the conventional mode. PMID- 21036421 TI - Effect of the chloro-substitution on lowering diabetic hyperglycemia of vanadium complexes with their permeability and cytotoxicity. AB - The effect of the chloro-substitution of dinuclear vanadium (V) complexes on lowering diabetic hyperglycemia was evaluated. The in vivo tests for hypoglycemic activity show that complex 2 at the dose of 10.0 and 20.0 mg V kg(-1), could significantly decrease the blood glucose level. Importantly, our results the chloro substituent increased the insulin-enhancing properties of the complex 2. The two vanadium compounds had permeability above 10(-5) cm/s. It suggested that two complexes permeate via a passive diffusion mechanism. It was also suggested that two complexes has better good lipophilic properties. The cytotoxicity of two complexes on Caco-2 cells suggested the chlorine atom at C4 of complex 2 increased cytotoxicity for vanadium complexes. PMID- 21036422 TI - Synthesis and antimicrobial evaluation of some fused heterocyclic [1,2,4]triazolo[3,4-b][1,3,4]thiadiazole derivatives. AB - A series of fused 1,2,4-triazoles with diphenylsulfone moiety are prepared utilizing 4-amino-5-[4-(4-X-phenylsulfonyl)phenyl]-4H-1,2,4-triazole-3-thiol 1 (X=H, Br). The latter on reaction with aromatic isothiocyanate in DMF, aromatic acid in POCl3 and CDI in dioxane gives five membered fused triazole derivatives 2a-c, 3a-c, 4a-g, 5a-g and 6a,b. The structures of newly synthesized compounds were confirmed on the basis of their elemental analysis and spectral data results (IR, 1H-and 13C NMR). New synthesized compounds were screened for their antimicrobial activities. The preliminary results revealed that some of the compounds exhibited promising antimicrobial activities. PMID- 21036423 TI - [Monitoring and precautions to take during treatment with a biological immunomodulator]. PMID- 21036425 TI - [Evaluation and management of thrombocytopenia]. PMID- 21036424 TI - [Off-label use of biological therapies in systemic diseases]. PMID- 21036426 TI - [How to measure proteinuria: 24-hour urine collection versus protein/creatinine ratio in a random urine sample?]. PMID- 21036427 TI - [Paraneoplastic neurological syndromes]. AB - Paraneoplastic neurological syndromes (PNS) are uncommon and defined by an acute or subacute neurological syndrome associated with a cancer. These syndromes often antedate the diagnostis of the underlying neoplasia that is usually not clinically evident. An early diagnosis is the main condition for a better neurological and carcinologic outcome. Subacute cerebellar ataxia, subacute sensitive neuropathy, limbic encephalomyelitis, Lambert-Eaton myasthenic syndrome, opsoclonus myoclonus, dermatopolymyositis and intestinal pseudo obstruction belong to the well-characterized PNS and their presence must lead to onconeuronal antibodies (ONA) detection. Treatment of the underlying neoplasia is the mainstay of treatment to obtain a better outcome. However, recent findings lead to consider immunological specific treatment according to the subtype of associated ONA. PNS associated with ONA targeting membrane antigens are thus usually responsive to immunomodulator therapies. Conversely, PNS associated with ONA targeting intracellular antigens are of poor outcome despite mild improvement under immunosuppressive therapies in some patients. PMID- 21036429 TI - Fitting in: a pervasive new graduate nurse need. AB - AIM: This qualitative study aims to provide insight into how Australian New Graduate Nurses (NGNs) experienced their transition to acute care nursing practice. METHOD: Nine NGNs each participated in three in-depth interviews conducted across their first year of practice. Constant comparative analysis was used to identify the emergent themes. FINDINGS: The desire to fit in (establishment of secure social bonds) with ward staff is an important element of NGN transition experiences. Fitting in was about feeling one's self to be part of a social group, and participants made it clear that their perceptions of their success in establishing secure and meaningful social bonds in each new ward was extremely important for their sense of being as NGNs. Current NGN Transition Programmes (NGNTPs) involve multiple ward rotations, increasing the demand for the NGN to fit in. Thus participants were engaged in a deeply personal transition experience that was not necessarily aligned with multiple ward rotations. CONCLUSIONS: Although NGNTPs have the word "transition" in their title, it may be that current programmes are more focussed on organisations' desire to "orient" NGNs to working within the acute care setting than facilitating personal transitions to practice. Further investigation of the impact of NGNTPs on NGNs and the associated multiple ward rotations is required. PMID- 21036428 TI - [Prescriptions of glycopeptides in 10 university hospitals in Paris area: a 1-day survey]. AB - PURPOSE: The prescription of glycopeptides (GP) was evaluated in hospitalized patients. METHODS: A 1-day survey was performed in 10 hospitals of the Ile-de France region regarding the prescription of GP. Characteristics of the included patients, indications of prescription and modalities of GP administration were studied independently of the prescribers. RESULTS: Overall, 90 patients (median age of 49 years [10 days-89 years]) were treated with a GP (vancomycin: 76; teicoplanin: 14). Indications of therapy included a microbiologically documented infection in 40 cases (44%), an empiric therapy in 44 cases (49%) and a prophylaxis in six cases (7%). In documented infections, main isolated pathogens were: coagulase-negative staphylococci (49%) and Staphylococcus aureus (32%) that were susceptible to methicilline in 27 and 26%, respectively. Vancomycin was administered intravenously (IV) in 71 cases (intermittent dosing in 41 patients (58%) and continuous infusion in 30 patients (42%), as central venous catheter lock in four patients and per os in one patient. In continuously infusion regimens, a loading dose at the initiation of treatment had been administered in 19 cases (63%). The median dosage the first day of curative treatment was <20mg/kg in 10 patients (20% of patients had normal renal function). Teicoplanin (median dosage: 8mg/kg, [3-13]) was IV infused in 86% of cases. Monitoring of serum GP concentrations was performed in only 58% of the cases (vancomycin: 47; teicoplanin: five). A low trough serum concentration was observed in 54% of the 52 monitored patients. The dosage of GP was readapted in only 55% of such cases. CONCLUSION: In this 1-day survey, we observed that GP administration was not optimal. Indeed, prolonged prescription of GP as empiric therapy was frequent, monitoring was not systematic, and prescribed dosages were often inadequate. PMID- 21036430 TI - Can YouTube enhance student nurse learning? AB - The delivery of nurse education has changed radically in the past two decades. Increasingly, nurse educators are using new technology in the classroom to enhance their teaching and learning. One recent technological development to emerge is the user-generated content website YouTube. Originally YouTube was used as a repository for sharing home-made videos, more recently online content is being generated by political parties, businesses and educationalists. We recently delivered a module to undergraduate student nurses in which the teaching and learning were highly populated with YouTube resources. We found that the use of YouTube videos increased student engagement, critical awareness and facilitated deep learning. Furthermore, these videos could be accessed at any time of the day and from a place to suit the student. We acknowledge that there are some constraints to using YouTube for teaching and learning particularly around the issue of unregulated content which is often misleading, inaccurate or biased. However, we strongly urge nurse educators to consider using YouTube for teaching and learning, in and outside the classroom, to a generation of students who are native of a rapidly changing digital world. PMID- 21036432 TI - Service user and carer involvement in student nurse selection: key stakeholder perspectives. AB - The aim of this study was to evaluate an innovation where service users and carers were involved in the recruitment of child and adult nursing students. Seventy candidates, four service users and carers and six academics who had been involved in the selection process took part in the study. A short questionnaire was administered to the nursing candidates. Two semi structured group interviews were undertaken, one with the service users and carers and another with the academics. Findings reveal that the involvement of service users and carers in student recruitment was largely viewed positively with all three major stakeholders supporting it. Nevertheless the academics were also mindful of the difficulties that may be encountered in the process. The key message to emerge from this study is that service user and carer involvement in student selection is not without its challenges but with careful planning can be beneficial for all involved. PMID- 21036431 TI - Nursing students' views on the effectiveness of problem-based learning. AB - A descriptive study was conducted with 28 nursing students in Macao and 23 nursing students in Shanghai to explore students' views on the effectiveness of problem-based learning (PBL). The PBL Evaluation Questionnaire was used. It used a 20-item self-report Likert scale with a 5-point response choice (1=ineffective and 5=very effective). The value of the content validity index tested by five experts was determined as one and the internal consistency (Cronbach's alpha) was 0.90. The test-retest reliability with a two-week internal check was 0.89. Two open-ended questions were asked to determine students' comments on the positive and negative features of PBL. The response rate was 100%. Overall, students considered PBL to be moderately effective with a mean of 3.58 (S.D.=0.52). Students from Macao considered PBL to be less effective than students from Shanghai. However, half of the Macao students and 21.74% of the Shanghai students indicated that PBL was a time-consuming and stressful process that involved an increased workload. A small number of students indicated that sometimes the information they received was vague and this resulted in a lack of student confidence. It is clear that the initial implementation of PBL is not always a smooth process. Tutors should be prepared to provide students with substantial support in developing their understanding of PBL, and help students develop appropriate strategies for coping and engaging in the PBL learning process. PMID- 21036433 TI - Healthcare organizations benefit by promoting BSN education. PMID- 21036434 TI - Effect of electrochemical treatment on high-flow vascular malformations in the maxillofacial region. AB - We explored the effect of electrochemical therapy for the treatment of high-flow venous malformations in the maxillofacial region in 32 patients. We used a method of anaesthesia that was suitable to the site and size of the lesion, and then inserted platinum needles into the lesion in a sterile environment. We protected the normal skin by inserting the cannulas into plastic sheaths, and connected the needles to an electrochemical machine. The common voltage, electric current, and amount of electricity were 6-8 V, 80-100 mA, and 10-20 C/cm(2), respectively. During a follow up period of two months to three years, 18 (56%) patients had a complete response, and 14 a partial response (44%). Electrochemical treatment is a simple, relatively atraumatic method of dealing with high-flow venous malformations that leaves no scars. PMID- 21036435 TI - The sternocleidomastoid perforator flap. AB - The conventional pedicled sternocleidomastoid (SCM) flap has a poor arc of rotation, limited volume and precarious vascularity. This report describes a new technique for raising a SCM flap based on the perforating vessels of the superior thyroid vascular pedicle. The upper and lower attachments of the sternocleidomastoid muscle are divided. Four medically and/or surgically compromised patients have successfully undergone reconstruction of hemiglossectomy (1), partial glossectomy (1) and rim of mandible (2) defects for malignancy. The arc of rotation of the SCM flap is greatly increased and the potential applications for the flap expanded. PMID- 21036436 TI - Face, neck, and eye protection: adapting body armour to counter the changing patterns of injuries on the battlefield. AB - Recent international papers have suggested an urgent need for new methods of protecting the face, neck, and eyes in battle. We made a systematic analysis to identify all papers that reported the incidence and mortality of combat wounds to the face, eyes, or neck in the 21st century, and any papers that described methods of protecting the face, neck, or eyes. Neck wounds were found in 2-11% of injuries in battle, and associated with high mortality, but no new methods of protecting the neck were identified. Facial wounds were found in 6-30% of injuries in battle, but despite the psychological effects of this type of injury only one paper suggested methods for protection. If soldiers wore existing eye protection they potentially reduced the mean incidence of eye injuries in combat from the 4.5% found in this analysis to 0.5%. Given the need to balance protection with the functional requirements of the individual soldier, a multidisciplinary approach is required. Military surgeons are well placed to work with material scientists and biomechanical engineers to suggest modifications to the design of both personal and vehicle-mounted protection. Further research needs is needed to find out how effective current methods of protecting the neck are, and to develop innovative methods of protecting the vulnerable regions of the neck and face. PMID- 21036437 TI - Wider excision margins for malignant melanoma. PMID- 21036438 TI - Use of narrow band imaging guidance in the management of oral erythroplakia. AB - Erythroplakia is an epithelial lesion that holds the highest risk of showing severe dysplasia or microinvasive carcinoma. The gold standard treatment is total excision to obtain a complete histopathological diagnosis. Traditionally this has been done by illumination of the lesion with white light, and resection with adequate margins. The difficulty with erythroplakia is that margins can be hard to delineate precisely, and even severe dysplasia can be seen with only subtle changes in the surface mucosa. Narrow band imaging is a novel technique that enhances the diagnostic potential of endoscopy. It highlights abnormalities in the superficial vasculature, which means that lesions such as oral erythroplakia can be identified more easily. We report its use in the identification of the full extent of lesions, and show its intraoperative advantages in obtaining resection margins free from disease. PMID- 21036439 TI - Maternity services in multi-cultural Britain: using Q methodology to explore the views of first- and second-generation women of Pakistani origin. AB - OBJECTIVE: to explore first- and second-generation Pakistani women's experiences of maternity services and the inter generational differences/comparisons. DESIGN: a retrospective Q methodology study of Pakistani women following childbirth. SETTING: two Children's Centres in an inner city in the West Midlands. PARTICIPANTS: women self-identified following distribution of information leaflets at Children's Centres. Fifteen women took part in interviews (Stage one) using a semi-structured design and 16 women participated in the completion of the Q grid sorting (Stage four). METHODS: a standard five-stage Q methodology process took place: (1) initial data were gathered using a combination of individual face to-face and focus group semi-structured community-based interviews (developing the concourse); (2) transcribed interviews were analysed for 'themes'; (3) the themes were reduced to 'statements' that reflected the overall content of the concourse using an unstructured evolving approach (giving the Q set); (4) participants were asked to sort the statements (Q sorting) according to a pre designed distribution grid providing individual participant response grids; and (5) the response grids were factor analysed using PQ Method (V2.11), which generates clusters of participants rather than clusters of variables. Factor loadings were calculated using factor analysis by principal components with varimax rotation. This produced a list of factors, each of which represents a 'story' of women's experiences of maternity services. Throughout the process, an Urdu interpreter was involved. FINDINGS: six factors were identified: (1) confidence and empowerment of women who had attended higher education and had family support; (2) isolation of some women from both family and maternity services; (3) women who had poor experiences of maternity services but good family support, and wanted opportunities to be involved in service development; (4) women with positive experiences of maternity care and influenced by traditional cultural practices; (5) importance of information and support from health-care professionals; and (6) importance of midwifery care to women. CONCLUSION: there were no clear inter generational differences identified, but a breadth of opinion and experience that seemed to be influenced by level of both education and social support was found. Whereas some women had few demands of maternity services, those who had less support and those with language barriers had additional needs. IMPLICATIONS FOR PRACTICE: care given should be based on individual need but given within a wider collaborative context in order to support women effectively. Increased maternity service user involvement would also be welcomed for future planning of maternity services. PMID- 21036440 TI - Compromised metamorphosis and thyroid hormone changes in wood frogs (Lithobates sylvaticus) raised on reclaimed wetlands on the Athabasca oil sands. AB - The wet landscape approach to oil sands tailings reclamation in the Athabasca Oil Sands region involves creating wetlands from fluid tailings in mined-out pits. We measured time to metamorphosis, thyroid hormone status, and detoxification enzyme (EROD) induction in Wood frog (Lithobates sylvaticus) tadpoles raised on reclaimed oil sands wetlands of different ages [young (<= 7 yr) vs. old (> 7 yr)] and compared data with tadpoles raised on reference (control) wetlands. Metamorphosis was delayed or never occurred in tadpoles raised in young tailings; those exposed to older tailings developed similarly to those in reference wetlands. Thyroid hormone disruption likely played an important role in the metamorphosis delay as the T3:T4 ratio was lowest in tadpoles raised in young, tailings-affected wetlands. Our findings suggest tailings wetlands become less toxic with age, and that these amphibians will be able to complete their life cycle in tailing wetlands that have sufficiently detoxified with age. PMID- 21036442 TI - Use of kidney function end points in kidney transplant trials: a systematic review. AB - BACKGROUND: Clinical trials in kidney transplantation are beginning to include markers of kidney function as end points now that traditional outcomes, such as acute rejection, become increasingly rare events. The frequency and type of kidney function end points used are unknown. STUDY DESIGN: Systematic review. SETTING & POPULATION: Randomized controlled trials in adult kidney transplant recipients reported in 5 major general medical journals and 5 major subspecialty journals in nephrology and transplantation between January 2003 and November 2008. SELECTION CRITERIA: Inclusion of at least one kidney function end point at least 1 month posttransplant. RESULTS: 133 (79%) of 169 randomized trials identified used a kidney function end point. Of these, 37 (28%) used one or more measures of kidney function as the primary end point, and 81 (61%), as a secondary end point. For the primary end point, 21 (57%) trials used a creatinine based estimated glomerular filtration rate (eGFR), 18 (49%) used serum creatinine level, and 7 (19%) used measured GFR. Overall, eGFR was an end point in 81 (61%) trials, and measured GFR, in 12 (9%) trials. LIMITATIONS: This review is limited by the poor quality of the included trials, with many not defining either primary or secondary end points. CONCLUSIONS: Measures of kidney function are used commonly as surrogate end points in kidney transplant trials, with eGFR becoming more frequently used over time. Further data are needed to properly validate these surrogate end points and fully understand their limitations when designing and interpreting randomized trials. PMID- 21036441 TI - Association of CKD with disability in the United States. AB - BACKGROUND: Little is known about disability in early-stage chronic kidney disease (CKD). STUDY DESIGN: Cross-sectional national survey (National Health and Nutrition Examination Survey 1999-2006). SETTING & PARTICIPANTS: Community-based survey of 16,011 noninstitutionalized US civilian adults (aged >=20 years). PREDICTOR: CKD, categorized as no CKD, stages 1 and 2 (albuminuria and estimated glomerular filtration rate [eGFR] >=60 mL/min/1.73 m2), and stages 3 and 4 (eGFR, 15-59 mL/min/1.73 m2). OUTCOME: Self-reported disability, defined by limitations in working, walking, and cognition and difficulties in activities of daily living (ADL), instrumental ADL, leisure and social activities, lower-extremity mobility, and general physical activity. MEASUREMENTS: Albuminuria and eGFR assessed from urine and blood samples; disability, demographics, access to care, and comorbid conditions assessed using a standardized questionnaire. RESULTS: Age-adjusted prevalence of reported limitations generally was significantly greater with CKD: for example, difficulty with ADL was reported by 17.6%, 24.7%, and 23.9% of older (>=65 years) and 6.8%, 11.9%, and 11.0% of younger (20-64 years) adults with no CKD, stages 1 and 2, and stages 3 and 4, respectively. CKD also was associated with greater reported limitations and difficulty in other activities after age adjustment, including instrumental ADL, leisure and social activities, lower extremity mobility, and general physical activity. Other demographics, socioeconomic status, and access to care generally only slightly attenuated the observed associations, particularly in older individuals; adjustment for cardiovascular disease, arthritis, and cancer attenuated most associations such that statistical significance no longer was achieved. LIMITATIONS: Inability to establish causality and possible unmeasured confounding. CONCLUSION: CKD is associated with a higher prevalence of disability in the United States. Age and other comorbid conditions account for most, but not all, of this association. PMID- 21036443 TI - Suicide, social integration, and masculinity in the U.S. military. AB - Reports indicate that suicide in the U.S. military has increased significantly in recent years. This increase has been attributed to a number of factors, including more frequent deployments, more relaxed screening of recruits, combat trauma, economic difficulty amongst soldiers, and the breakdown of interpersonal relationships. In this article, we add an element that we believe is crucial to an understanding of military suicide: the socio-cultural environment of the military itself. In particular, we examine the role that the masculine ideologies governing military life play in the internalization of individual frustrations and in suicidal behavior. Suicide investigators often have ignored the role of masculine ideologies in military suicide because of the assumption that suicide results from social disintegration. In contrast, we argue that military suicide is driven largely by excessive social integration. From this perspective, current explanations of military suicide are constrained by gender and etiological assumptions. Finally, this paper suggests the implications of these findings for designing more effective prevention programs for military suicide. PMID- 21036444 TI - Aboriginal peoples, health and healing approaches: the effects of age and place on health. AB - For demographic reasons and as a result of a number of high profile health incidents in recent years, much of the health research and policy focus is on the younger cohorts of Aboriginal peoples in Canada. A critical examination of recent demographic trends reveals, however, that older cohorts of the Aboriginal population are increasing at a faster rate than younger cohorts, primarily due to improvements in life expectancy and declining fertility rates. Yet, there are surprisingly few health studies that have recognized the aging of the Aboriginal population. The overall goal of this paper is to examine differences in health status, use of conventional health care and traditional approaches to healing between older and younger cohorts of the Aboriginal population as well as to examine the importance of age as a determinant of health and health care use. Using data from the 2001 Statistics Canada Aboriginal Peoples Survey and contingency tables and logistic regression, the results demonstrate that older Aboriginal people face unique challenges - e.g. loss of traditional approaches to healing, geographic isolation, identity politics, constitutional and legal divisions within the Aboriginal community - with respect to their health and access to health services. These outcomes result from a colonial past and contemporary policies that affect all Aboriginal people. PMID- 21036445 TI - Chinese and American employers' perspectives regarding hiring people with behaviorally driven health conditions: the role of stigma. AB - Work opportunities for people with behaviorally driven health conditions such as HIV/AIDS, drug abuse, alcohol abuse, and psychosis are directly impacted by employer perspectives. To investigate this issue, we report findings from a mixed method design involving qualitative interviews followed by a quantitative survey of employers from Chicago (U.S.), Beijing (China), and Hong Kong (China). Findings from qualitative interviews of 100 employers were used to create 27 items measuring employer perspectives (the Employer Perspective Scale: EPS) about hiring people with health conditions. These perspectives reflect reasons for or against discrimination. In the quantitative phase of the study, representative samples of approximately 300 employers per city were administered the EPS in addition to measures of stigma, including attributions about disease onset and offset. The EPS and stigma scales were completed in the context of one of five randomly assigned health conditions. We weighted data with ratios of key demographics between the sample and the corresponding employer population data. Analyses showed that both onset and offset responsibility varied by behaviorally driven condition. Analyses also showed that employer perspectives were more negative for health conditions that are seen as more behaviorally driven, e.g., drug and alcohol abuse. Chicago employers endorsed onset and offset attributions less strongly compared to those in Hong Kong and Beijing. Chicago employers also recognized more benefits of hiring people with various health conditions. The implications of these findings for better understanding stigma and stigma change among employers are considered. PMID- 21036446 TI - [Which breast reconstruction procedure provides the best long-term satisfaction?]. AB - INTRODUCTION: Patient satisfaction is a good indicator to evaluate the success of breast reconstruction. The aim of this study was to compare the long-term satisfaction in patients who underwent four breast reconstruction techniques. PATIENT AND METHODS: Self-evaluation was achieved by patients in 147 breast reconstructions using a four-point score: very disappointed, disappointed, satisfied and very satisfied. The mean follow-up was 5.3 year (1 to 21.5 year). The surgical procedures used were: transverse rectus abdominis myocutaneous flap (TRAM) 15%, autologous latissimus dorsi flap (ALD) 14%, latissimus dorsi flap with implant (LDI) 32% and implant alone 39%. Patients' satisfaction was compared regarding the type of surgical procedure, the postoperative follow-up time; the immediate or delayed breast reconstruction and the radiation history. RESULTS: Thirty-five percent of the patients were very satisfied with their operation, 54% were satisfied, 7% were disappointed and 4% very disappointed. After a 5-year follow-up, autologous flaps showed better results (P<0.001). Patients were more satisfied with TRAM flaps than with surgical techniques using latissimus dorsi flaps (ALD and LDI). Patients treated with implants alone were statistically less satisfied. Only in the implant series, patient satisfaction decreased significantly with time (P<0.001) and preoperative radiation (P=0.005). CONCLUSIONS: Flap-based breast reconstructions show consistent long-term satisfaction although the surgery is initially more demanding. Our study matches the latest trends in the use of free perforator flaps for breast reconstruction. Indeed, these procedures combine good satisfaction and minor sequelae at the donor site. PMID- 21036447 TI - [Description of an original conservative method for the surgical management of the Blauth IIIb thumb hypoplasia: "relative lengthening - thumb stabilization"]. AB - PROBLEMATIC: Thumb hypoplasia is a rare congenital hand disorder. Despite the recent clarifications concerning many surgical indications, dealing with Blauth IIIb type remains a polemic subject. We hereby suggest "The relative lengthening thumb stabilization", an original and simple conservative surgery technique for the Blauth IIIb type, in order to satisfy parents and big kids requests of a "five fingered hand". The whole hypoplastic thumb is lowered in a way that lengthens it relatively. An intentional pseudarthrosis is performed between the first metacarpal base and the second metacarpal diaphysis, creating a "new trapeziometacarpal joint". PATIENTS AND METHODS: The suggested technique was performed on four IIIb type hypoplasic thumbs of three kids since 1997. RESULTS: The average postoperative follow-up is 9.6years (3.5 to 12.5years). The average Kapandji score is 5.75 (5 to 6). The key pinch prehension strength is by 21.5% in relation to the normal hand and the global prehension strength (according to Jamar Test) is by 67%. The global pinch is possible and natural in all cases. DISCUSSION AND CONCLUSION: The surgical management of the type IIIb thumb hypoplasia is a real challenge. We regard this technique of relative lengthening with thumb stabilization as an interesting alternative to the other microsurgical conservative surgeries. PMID- 21036448 TI - [Aortodigestive fistula and septic wound of the lower leg. A case report]. AB - An aortodigestive fistula can be revealed by a peripheral septic wound when patient have aortic endovascular prosthesis. Our clinical case is about a 69-year old patient with an abscess of the lateral aspect of his left lower limb. He has been treated few years ago for an aorto-abdominal anevrysm by an aortobifemoral prosthesis. In spite of a negative initial assessment for an aortodigestive fistula, anaerobic germs were found into the abscess. The initial treatment associated debridement, negative pressure therapy, dermal substitute and a split thickness skin graft for the loss of cutaneous substance. Months later, in front of an unexplained skin healing delay and fever, we realised new assessment bringing to light an aortodigestive fistula. Furthermore, the local bacterial samples from the wound and the hemocultures found both a lot of Escherichia Coli. The change of the aorto-bifemoral prosthesis and the cure of the aortodigestive fistula allowed the complete healing of the loss of cutaneous substance of the leg. The aortodigestive fistulas have a very high mortality. Because of their difficult diagnosis, their clinical suspicion has to start a complete medical assessment. Every septic wound when patients have vascular prosthesis is suggestive of an aortodigestive fistula. PMID- 21036449 TI - The association between intra-arrest therapeutic hypothermia and return of spontaneous circulation among individuals experiencing out of hospital cardiac arrest. AB - INTRODUCTION: Therapeutic hypothermia has been shown to improve both mortality and neurologic outcomes following pulseless ventricular tachycardia and fibrillation. Animal data suggest intra-arrest induction of therapeutic hypothermia (IATH) improves frequency of return of spontaneous circulation (ROSC). Our objective was to evaluate the association between IATH and ROSC. METHODS: This was a retrospective analysis of individuals experiencing non traumatic cardiac arrest in a large metropolitan area during a 12-month period. Six months into the study a prehospital IATH protocol was instituted whereby patients received 2000ml of 4 degrees C normal saline directly after obtaining IV/IO access. The main outcome variables were prehospital ROSC, survival to admission, and to discharge. A secondary analysis was conducted to assess the relationship between the quantity of cold saline infused and the likelihood of prehospital ROSC. RESULTS: 551 patients met inclusion criteria with all the elements available for data analysis. Rates of prehospital ROSC were 36.5% versus 26.9% (OR 1.83; 95% CI 1.19-2.81) in patients who received IATH versus normothermic resuscitation respectively. While the frequency of survival to hospital admission and discharge were increased among those receiving IATH, the differences did not reach statistical significance. The secondary analysis found a linear association between the amount of cold saline infused and the likelihood of prehospital ROSC. CONCLUSION: The infusion of 4 degrees C normal saline during the intra-arrest period may improve rate of ROSC even at low fluid volumes. Further study is required to determine if intra-arrest cooling has a beneficial effect on rates of ROSC, mortality, and neurologic function. PMID- 21036450 TI - Correct use of cricoid pressure in pre-hospital emergency intubation. PMID- 21036451 TI - Electrical cardioversion - misinterpretation of the R-wave. PMID- 21036452 TI - The unit gram meter remains an incorrect unit for the ventricular stroke work. PMID- 21036454 TI - Dispatcher-assisted telephone cardiopulmonary resuscitation using a French language compression-only protocol in volunteers with or without prior life support training: A randomized trial. AB - OBJECTIVES: Due to the recent interest in hands-only protocols for dispatcher assisted cardiopulmonary resuscitation (CPR) and the lack of any validated algorithms in French, our primary objective was to evaluate a new French-language protocol in terms of its efficacy to help previously untrained volunteers in performing basic life support efforts of appropriate quality, and secondarily to investigate its potential utility in subjects with previous training. METHODS: Untrained volunteers were recruited among adults in a public movie centre and previously trained volunteers among undergraduate nursing students. Participants were randomly assigned to 'phone CPR' versus 'no phone CPR' by drawing sets of envelopes. Primary outcome measures were the results of the Cardiff evaluation test; the secondary measures were global scoring of a complete 5min period of CPR, in a manikin model of cardiac arrest. RESULTS: Out of 146 volunteers assessed for eligibility, 36 previously untrained candidates declined participation. 110 participants, distributed into four groups, completed the study: the previously untrained non-guided group (group A, n=30), the previously untrained guided group (group B, n=30), the previously trained non-guided group (group C, n=25) and the previously trained guided group (group D, n=25). Results of the Cardiff test and global evaluation of CPR performance revealed a significant improvement in group B as compared with group A, approaching the level of the group C. Previously trained guided bystanders had the best CPR scores, notably because of an improvement in the quality of airway management. CONCLUSION: When used by dispatchers, this new French-language algorithm offers the opportunity to help previously untrained bystanders initiate CPR. The same protocol may serve to guide volunteers with prior basic life support training to reach their best CPR performance. PMID- 21036453 TI - Histone deacetylase inhibitors prevent apoptosis following lethal hemorrhagic shock in rodent kidney cells. AB - BACKGROUND: We have previously demonstrated that treatment with histone deacetylase inhibitors (HDACI), such as valproic acid (VPA) and suberoylanilide hydroxamic acid (SAHA), can improve survival after hemorrhagic shock in animal models. Hemorrhage results in hypoacetylation of proteins which is reversed by HDACI. These agents are known to acetylate insulin receptor substrate-I (IRS-I), which in turn activates the Akt survival pathway. This study investigated whether HDACI exert their beneficial effects through the Akt survival pathway. METHODS: Wistar-Kyoto rats (N=21) underwent hemorrhage (60% blood loss) and were randomized into 3 groups; no resuscitation (NR), and treatment with VPA or SAHA. Kidneys were harvested at 1, 6, and 24h after HDACI treatment and analyzed for acetylated histone 3 at lysine 9 residue (Ac-H3K9), phosphorylated Akt (phospho Akt), BAD and Bcl-2 proteins. RESULTS: Hemorrhaged animals were in severe shock, with mean arterial pressures of 25-30mmHg and lactic acid 7-9mg/ml. Only animals treated with VPA and SAHA survived to the 6- and 24-h timepoints. Treatment with HDACI produced a biologic effect on rat kidney cells inducing acetylation of histone H3K9, which peaked after 1h of treatment, and was statistically significant in the VPA group (p=0.01) compared to NR. Phospho-Akt protein increased in the VPA group with a reciprocal decrease in the pro-apoptotic BAD protein in both groups which was statistically significant in the VPA group after 1h (p=0.007) and 24h (p=0.006) of treatment and in the SAHA group after 24h of treatment (p=0.028). Anti-apoptotic Bcl-2 protein markedly increased after 6 (p=0.04) and 24h (p=0.014) of VPA treatment. Bcl-2 also increased in the SAHA group, but failed to reach statistical significance. CONCLUSION: Treatment with HDACI increases phosphorylation of Akt with a subsequent decrease in the pro apoptotic BAD protein. The above mechanism facilitates the action of anti apoptotic protein Bcl-2. HDACI protect kidney cells subjected to hemorrhagic shock in rodents through the Akt survival pathway. PMID- 21036455 TI - History of accidental hypothermia. AB - Death from exposure to cold has been recognised for thousands of years but hypothermia as a clinical condition was not generally recognised until the mid 20th century and then only in extreme conditions such as immersion in cold water or snow. In the UK, hypothermia in less extreme conditions was not generally recognised until the 1960s. Recognition of hypothermia required the temperature to be measured and this did not become a clinical tool until the late 1800s and it was not used routinely until the early 1900s. Although John Hunter and James Curry did some physiological experiments in the 1700s, detailed physiological experiments were not done until the early 20th century and the use of therapeutic hypothermia for malignancy and in anaesthesia in the 1930s and 1940s provided more impetus for investigating the physiology of hypothermia in humans and familiarising the medical profession with measuring core temperatures. PMID- 21036456 TI - Developing NEWS. PMID- 21036457 TI - The effect of a cellular-phone video demonstration to improve the quality of dispatcher-assisted chest compression-only cardiopulmonary resuscitation as compared with audio coaching. AB - OBJECTIVE: Bystander cardiopulmonary resuscitation (CPR) has shown to significantly improve the survival of cardiac-arrest victims. Dispatcher assistance increases the number of bystanders who perform CPR, but the quality of CPR remains unsatisfactory. This study was conducted to assess the effect of video coaching on the performance of CPR by untrained volunteers when compared with traditional audio instruction in simulated cardiac arrests. METHODS: Adult volunteers were randomised to receive audio-assisted instructions (audio group=39), or video-demonstrated instructions (video group=39) via cellular phones on how to perform chest compressions on mannequins. Then, the volunteers' performances were video-recorded. The quality of CPR was evaluated by reviewing the videos and mannequin reports. RESULTS: For the video group, the chest compression rate was more optimal (99.5min(-1) vs. 77.4min(-1), P<0.01) and the time from the initial phone call to the first compressions was shorter (184s vs. 211s, P<0.01). The depth of compressions was deeper in the audio group (31.3mm vs. 27.5mm, P=0.21), but neither group performed the recommended depth of compression. The hand positions for compression were more appropriate in the video group (71.8% vs. 43.6%, P=0.01). As many as 71.8% of the video group had no 'hands-off' events when performing compression (vs. 46.2% for the audio group, P=0.02). CONCLUSIONS: Instructions from the dispatcher, along with a video demonstration of CPR, improved the time to initiate compression, the compression rate and the correct hand positioning. It also reduced the 'hands-off' events during CPR. However, emphasised instructions by video may be needed to increase the depth of compressions. PMID- 21036458 TI - The importance of surface area for the cooling efficacy of mild therapeutic hypothermia. AB - AIM OF THE STUDY: Mild hypothermia after cardiac arrest should be induced as soon as possible. There is a need for improved feasibility and efficacy of surface cooling in ambulances. We investigated which and how much area of the body surface should be covered to guarantee a sufficient cooling rate. METHODS: Each of five adult, human-sized pigs (88-105kg) was randomly cooled in three phases with pads that covered different areas of the body surface corresponding to humans (100% or 30% [thorax and abdomen] or 7% [neck]). The goal was to quickly lower brain temperature (Tbr) from 38 to 33 degrees C within a maximum of 120min. Linear regression analysis was used to test the association between cooling efficacy and surface area. Data are presented as mean+/-standard deviation. RESULTS: The 100% and 30% cooling pads decreased the pigs' Tbr from 38 to 33 degrees C within 33+/-7min (8.2+/-1.6 degrees C/h) and 92+/-24min (3.6+/-1.1 degrees C/h). The 7% achieved a final Tbr of 35.8+/-0.7 degrees C after 120min (1.1+/-0.4 degrees C/h). The 30% and 7% cooling surface areas achieved 37+/-11% and 15+/-7% of the cooling rate compared to the 100% cooling pads. For every additional percent of surface area cooled, the cooling rate increased linearly by 0.07 degrees C/h (95% CI 0.05-0.09, p=0.001). No skin lesions were observed. CONCLUSIONS: The cooling pads were effective and safe for rapid induction of mild hypothermia in adult, human-sized pigs, depending on the percentage of body surface area covered. Covering only the neck, chest, and abdomen might achieve satisfactory cooling rates. PMID- 21036459 TI - Self-organization of G-quadruplex structures in the hTERT core promoter stabilized by polyaminic side chain perylene derivatives. AB - hTERT core promoter regulates telomerase transcription in human cells, thus its structural features are of large interest. We have found that the G-rich hTERT core promoter region, corresponding to the major DNase I hypersensitive site in chromatin organization, contains nine putative G-quadruplex forming sequences (PQS) and is unfavorable for nucleosome formation. Here we show that four PQS are effectively able to form stable parallel intramolecular G-quadruplexes, using PAGE and CD spectroscopy analysis. The PQS-region, as a whole, appears to be organized in three self-interacting G-quadruplexes, probably giving rise to a helicoidal superstructure, as shown by CD and polymerase stop assay. POL-HPDI drugs, that we previously found useful in selectively stabilizing telomeric G quadruplex, are able to stabilize both the single intramolecular G-quadruplex and the PQS-region superstructure. The features of their induced CD spectra suggest that POL-HPDIs bind to single G-quadruplexes and to whole PQS-region superstructure, mainly by end-stacking interactions. PMID- 21036460 TI - Sox2 expression is maintained while gastric phenotype is completely lost in Cdx2 induced intestinal metaplastic mucosa. AB - Sox2 is closely related to the gastric phenotype. Sox2 plays a pivotal role in gastric epithelial differentiation in the adult. Sox2 expression is reduced in Helicobacter pylori-associated intestinal metaplastic change of the gastric epithelium. The gastric mucosa is replaced by intestinal metaplastic mucosa in the stomach of caudal type homeobox 2 (Cdx2)-transgenic mice. The aim of this study was to use Cdx2-transgenic mice to investigate: (i) Sox2 expression in the intestinal metaplastic mucosa of the Cdx2-transgenic mouse stomach; and (ii) the relationship between Sox2 and Cdx2. Quantitative real-time PCR was performed to determine Sox2, Cdx2, Muc5Ac, and alkaline phosphatase mRNA expression levels and single- or double-label immunohistochemistry was used to evaluate the localization of Sox2, Cdx2, gastric mucin and alkaline phosphatase activity. We determined that Sox2 mRNA in the intestinal metaplastic mucosa of the Cdx2 transgenic mouse stomach was expressed 3.5-fold compared to the normal mouse stomach. Immunohistochemical analysis showed that the same cells in the intestinal metaplastic mucosa expressed both Cdx2 and Sox2. Gastric mucin was not expressed while alkaline phosphatase activity was recognized in the intestinal metaplastic mucosa in spite of the Sox2 expression. Cdx2 increased the transcriptional activity of the Sox2 gene, and Sox2 increased the transcriptional activity of the Muc5Ac gene, which was reduced by cotransfecion of Cdx2 together with Sox2 in the human gastric carcinoma cell line AGS. In conclusion, Sox2 expression is maintained while gastric phenotype is completely lost in the intestinal metaplastic mucosa of Cdx2-transgenic mouse stomach. PMID- 21036461 TI - Evaluation of compost blankets for erosion control from disturbed lands. AB - Soil erosion due to water and wind results in the loss of valuable top soil and causes land degradation and environmental quality problems. Site specific best management practices (BMP) are needed to curb erosion and sediment control and in turn, increase productivity of lands and sustain environmental quality. The aim of this study was to investigate the effectiveness of three different types of biodegradable erosion control blankets- fine compost, mulch, and 50-50 mixture of compost and mulch, for soil erosion control under field and laboratory-scale experiments. Quantitative analysis was conducted by comparing the sediment load in the runoff collected from sloped and tilled plots in the field and in the laboratory with the erosion control blankets. The field plots had an average slope of 3.5% and experiments were conducted under natural rainfall conditions, while the laboratory experiments were conducted at 4, 8 and 16% slopes under simulated rainfall conditions. Results obtained from the field experiments indicated that the 50-50 mixture of compost and mulch provides the best erosion control measures as compared to using either the compost or the mulch blanket alone. Laboratory results under simulated rains indicated that both mulch cover and the 50-50 mixture of mulch and compost cover provided better erosion control measures compared to using the compost alone. Although these results indicate that the 50-50 mixtures and the mulch in laboratory experiments are the best measures among the three erosion control blankets, all three types of blankets provide very effective erosion control measures from bare-soil surface. Results of this study can be used in controlling erosion and sediment from disturbed lands with compost mulch application. Testing different mixture ratios and types of mulch and composts, and their efficiencies in retaining various soil nutrients may provide more quantitative data for developing erosion control plans. PMID- 21036462 TI - Evaluation of Fenton and ozone-based advanced oxidation processes as mature landfill leachate pre-treatments. AB - Fenton treatment (Fe(2+)/H(2)O(2)) and different ozone-based Advanced Oxidation Processes (AOPs) (O(3), O(3)/OH(-) and O(3)/H(2)O(2)) were evaluated as pre treatment of a mature landfill leachate, in order to improve the biodegradability of its recalcitrant organic matter for subsequent biological treatment. With a two-fold diluted leachate, at optimised experimental conditions (initial pH 3, H(2)O(2) to Fe(2+) molar ratio of 3, Fe(2+) dosage of 4 mmol L(-1), and reaction time of 40 min) Fenton treatment removed about 46% of chemical oxygen demand (COD) and increased the five-day biochemical oxygen demand (BOD(5)) to COD ratio (BOD(5)/COD) from 0.01 to 0.15. The highest removal efficiency and biodegradability was achieved by ozone at higher pH values, solely or combined with H(2)O(2). These results confirm the enhanced production of hydroxyl radical under such conditions. After the application for 60 min of ozone at 5.6 g O(3)h( 1), initial pH 7, and 400 mg L(-1) of hydrogen peroxide, COD removal efficiency was 72% and BOD(5)/COD increased from 0.01 to 0.24. An estimation of the operating costs of the AOPs processes investigated revealed that Fe(2+)/H(2)O(2) was the most economical system (8.2 ? m(-3)g(-1) of COD removed) to treat the landfill leachate. This economic study, however, should be treated with caution since it does not consider the initial investment, prices at plant scale, maintenance and labour costs. PMID- 21036463 TI - Vardenafil decreases bladder afferent nerve activity in unanesthetized, decerebrate, spinal cord-injured rats. AB - BACKGROUND: Phosphodiesterase type 5 inhibitors (PDE5-Is) improve storage symptoms in benign prostatic hyperplasia patients, despite a lack of effect on peak urinary flow rate. Moreover, vardenafil improves urodynamic parameters in spinal cord-injured (SCI) patients with neurogenic detrusor overactivity (NDO). SCI rats also display NDO characterized by nonvoiding contractions (NVCs) during bladder filling, resulting in an increased bladder afferent nerve firing (BANF). OBJECTIVE: We postulated that vardenafil could improve urodynamic parameters by reducing BANF. The effect of vardenafil has been investigated on intravesical pressure by cystometry experiments while recording BANF in response to bladder filling. DESIGN, SETTING, AND PARTICIPANTS: Complete T7-T8 spinalization was performed in 15 female adult Sprague-Dawley rats (250-275 g). MEASUREMENTS: At 21 29 d postspinalization, fine filaments were dissected from the L6 dorsal roots and placed across a bipolar electrode. Bladder afferent nerve fibers were identified by electrical stimulation of the pelvic nerve and bladder distension. SCI rats were decerebrated before cystometry experiments. Bladders were filled to determine the maximal bladder filling volume (BFV) for each rat. Then, after bladder stabilization at 75% of maximal BFV, saline (n=7) or vardenafil 1 mg/kg (n=8) was delivered intravenously. NVCs and BANF were recorded for 45 min. RESULTS AND LIMITATIONS: In all SCI rats, BANF was already present and regular at resting conditions (26.2+/-4.1 spikes per second). During bladder filling, intravesical pressure (IVP) slowly increased with transient NVCs superimposed. Concomitantly, BANF progressively increased up to 2.4-fold at maximal BFV (2.08+/ 0.24 ml). After stabilization at submaximal BFV, BANF was increased by 186+/-37%. Vardenafil injection induced an immediate decrease in NVCs compared to saline (p<0.001) and BANF (52% decrease vs 28% in saline after 45 min; p<0.001). CONCLUSIONS: Systemic vardenafil reduced both NVCs and BANF in unanesthetized, decerebrate, SCI rats. These findings provide new insights into the mechanism of action by which PDE5-Is improve storage symptoms in SCI patients. PMID- 21036464 TI - Pentoxifylline promotes recovery of erectile function in a rat model of postprostatectomy erectile dysfunction. AB - BACKGROUND: Cavernous nerve (CN) injury during radical prostatectomy (RP) causes CN degeneration and secondary penile fibrosis and smooth muscle cell (SMC) apoptosis. Pentoxifylline (PTX) is a phosphodiesterase inhibitor that further inhibits multiple cytokine pathways involved in nerve degeneration, apoptosis, and fibrosis. OBJECTIVES: To evaluate whether PTX enhances erectile function in a rat model of CN injury. DESIGN, SETTING AND INTERVENTIONS: Forty male Sprague Dawley rats underwent CN crush injury and were randomized to oral gavage feeding of phosphate-buffered saline (vehicle) or PTX 25, PTX 50, or PTX 100 mg/kg per day. Ten animals underwent sham surgery and received vehicle treatment. Treatment continued for 28 d, followed by a wash-out period of 72 h. An additional eight rats underwent resection of the major pelvic ganglion (MPG) for tissue culture and examination of direct effects of PTX on neurite sprouting. MEASUREMENTS: Intracavernous pressure recording on CN electrostimulation, immunohistologic examination of the penis and the CN distal to the injury site, and length of neurite sprouts in MPG culture. RESULTS: Daily oral gavage feeding of PTX resulted in significant improvement of erectile function compared to vehicle treatment in all treated groups. After treatment with PTX 50 and PTX 100 mg/kg per day, the expression of neuronal nitric oxide synthase in the dorsal penile nerve was significantly higher than in vehicle-treated rats. Furthermore, PTX treatment prevented collagen deposition and SMC loss in the corpus cavernosum. In the CN, signs of Wallerian degeneration were ameliorated by PTX treatment. MPG culture in medium containing PTX resulted in a significant increase of neurite length. CONCLUSIONS: PTX treatment following CN injury in rats improved erectile recovery, enhanced nerve regeneration, and preserved the corpus cavernosum microarchitecture. The clinical availability of this compound merits application in penile rehabilitation studies following RP in the near future. PMID- 21036465 TI - Cost of acute ischemic and hemorrhagic stroke in Turkey. AB - OBJECTIVE: The aim of this study is to examine the direct medical costs and outcomes of patients with stroke. MATERIAL AND METHODS: The records of the patients admitted with ischemic and hemorrhagic stroke to the University of Trakya, School of Medicine, Department of Neurology were reviewed retrospectively in year 2007. Direct medical costs (total costs, radiological, laboratory, medicine, and other) were calculated, additionally cost per life saved and per life-year saved were calculated for stroke patients. RESULTS: The study group consisted of 328 patients (169 male/159 female) and mean age was 66.5 +/- 12.4 years. Length of hospital stay was 10.7 +/- 7.5 days. Mortality rate was 20.4% and the mRS score of the patients was 3.2 +/- 2.1. The average cost of stroke was US$ 1677 +/- 2964 (29.9% medicine, 19.9% laboratory, 12.8% neuroimaging, and 38% beds and staff). Cost per life saved and per life-year saved were US$ 2108 and US$ 1070, respectively. CONCLUSION: This is the first study in order to determine direct medical cost of stroke in Turkey, therefore, it may be guideline for disease-cost management of stroke. PMID- 21036467 TI - Promising role of [18F] fluorocholine PET/CT vs [18F] fluorodeoxyglucose PET/CT in primary brain tumors-early experience. AB - Primary brain tumors (PBT), in particular gliomas, are among the most difficult neoplasms to treat, necessitating good quality imaging to guide clinicians at many junctures. Current imaging modalities, including [18F] fluorodeoxyglucose (FDG) PET/CT, MRI and MR spectroscopy (MRS), have various limitations, particularly with regard to differentiating tumor from radiation induced necrosis (RIN) and from normal cerebral metabolic uptake. [18F] fluorocholine (FCH) is an analog of choline with potentially optimal imaging characteristics, as pharmacokinetic studies with FCH conducted in patients showed minimal FCH uptake by normal brain parenchyma, whereas high-grade tumors are known to have increased choline uptake. We present two cases of our early experience with FCH PET/CT for patients with PBT and discuss the potential use and comparative limitations of this imaging modality. PMID- 21036468 TI - Targeting apoptosis pathways in childhood malignancies. AB - Evasion of apoptosis (programmed cell death) is a characteristic feature of human cancers including childhood malignancies. Since cytotoxic therapies such as chemotherapy or radiotherapy trigger apoptosis as a primary mechanism of action, resistance to apoptosis can also lead to treatment resistance. Studies on apoptosis pathways in childhood malignancies yielded a series of key molecules that can now be exploited as molecular targets for the development of targeted therapies. This strategy is anticipated to open novel perspectives for more effective treatment options for children with cancer. PMID- 21036469 TI - Targeting apoptotic and autophagic pathways for cancer therapeutics. AB - Apoptosis and autophagy are genetically regulated, evolutionarily-conserved processes that regulate cell fate; however, apoptosis invariably contributes to cancer cell death, whereas autophagy plays the Janus role of cancer cell survival and death. In this review, we firstly focus on targeting cancer cells via several key apoptotic pathways for anti-cancer therapy. Additionally, we demonstrate that some autophagic pathways play dual roles in cancer, and further elucidate the intricate relationship between apoptosis and autophagy. In summary, these findings may ultimately allow biologists to harness apoptotic and autophagic pathways as novel targets for cancer therapeutics. PMID- 21036470 TI - Management of arsenic-accumulated waste from constructed wetland treatment of mountain tap-water. AB - Arsenic-contaminated mountain tap water supply in Ron Phibun District, Nakorn Si Thammarat Province, Thailand poses a health hazard. Arsenic was removed using a constructed wetland (CW) system, in which the treated contaminated tap water was sedimented in 3 consecutive ponds before entering into the CW ponds, containing either Cyperus spp. or Colocasia esculenta. Following 1 year of operation both plants had similar ability to remove arsenic from mountain tap water. Arsenic was mostly concentrated at the roots of both plants. Arsenic in C. esculenta leaves was allowed to leach out in freshwater for 149 days, but the level (0.05 mg L( 1)) was much lower than standard guidelines for industrial discharge. For Cyperus spp., young shoots were utilized as ornamental plants. As the sediments contained high arsenic levels, they were converted by a solidification/stabilization (S/S) system into cement-containing blocks, which after curing for 21 days produced arsenic leaching at levels that did not require a secure landfill for storage. The success of this study demonstrated that CW combined with appropriate S/S system is a suitable approach for Thailand in removing arsenic from contaminated water. PMID- 21036471 TI - Study on adsorption and desorption properties of the starch grafted p-tert-butyl calix[n]arene for butyl Rhodamine B solution. AB - The adsorbents of starch grafted p-tert-butyl-calix[4,6,8]arene-SGCn (SGC4, SGC6, SGC8) are prepared. The products are characterized by FTIR, elemental analysis, thermal gravimetric analysis and scanning electron microscope. Static adsorption behavior is studied by using SGC8 as adsorbent, butyl Rhodamine B (BRB) solution as simulation dye wastewater. The adsorption of BRB onto SGC8 fits the second order kinetic model and the apparent adsorption rate constant is 0.002 g mg( 1)min(-1) at 25 degrees C. The equilibrium adsorption data are interpreted using Langmuir and Freundlich models. The adsorption of BRB onto SGC8 is better represented by the Langmuir equation. The thermodynamic parameters for the adsorption reaction are calculated through van't Hoff analysis. The adsorbent may be easily regenerated by using ethanol solution as desorption agent to extract dye from SGC8. The rate of desorption of BRB is dependent on the concentration of ethanol and the temperature. SGC8 exhibits excellent adsorption and desorption properties toward dye molecule. The new-style adsorbent of SGC8 is regarded as a potential adsorbent to deal with dye or organic wastewater. PMID- 21036472 TI - Defluoridation behavior of nanostructured hydroxyapatite synthesized through an ultrasonic and microwave combined technique. AB - The absorption performance of a nano-structured hydroxyapatite produced from a combined ultrasonic and microwave technique was examined for the removal of fluoride from contaminated water. The effect of physical and chemical parameters such as initial pH, contact time, initial fluoride concentration and temperature were investigated. The results indicated that the equilibrium adsorption data followed both the Langmuir and Freundlich isotherms, with a maximum monolayer adsorption capacity of 5.5mg/g at 298K. In addition, the kinetic studies have shown that the fluoride adsorption data followed a pseudo-second order model and that the intra-particle diffusion process played a significant role in determining the rate. The thermodynamic analysis also established that the adsorption process was endothermic and spontaneous. The initial and final fluoride loaded nano-hydroxyapatite samples were characterized using FESEM, TEM, XRD, FTIR and XPS methods. The analysis revealed that structural changes to the adsorbent had taken place. PMID- 21036473 TI - Diethylene glycol removal by Echinodorus cordifolius (L.): the role of plant microbe interactions. AB - This work presents the use of the plant Echinodorus cordifolius for remediating diethylene glycol (DEG) contaminated waters. The potential of this plant for treating DEG wastewater in a remediation system was observed. We found that E. cordifolius was able to remove DEG from wastewater, decrease the pH to neutral and remove approximately 95% of the chemical oxygen demand within 12 days. The plants can grow well in DEG wastewater, as indicated by their root and leaf biomass, which was found to be statistically similar to control. Wilting, chlorosis and necrosis were observed in DEG-treated plants, but the relative water content was not significantly different between control and treated plants, suggesting that the plants were able to take up and tolerate DEG present in the wastewater. Plant roots changed to black colour during experimental period. The fluorescence in situ hybridisation and bacterial enrichment confirmed that 4.30 * 10(5) cells/g of sulphate reducing bacteria and 9.30 * 10(8) cells/g of acid producing bacteria were found associated with the plant roots. Furthermore, volatile fatty acids were found in non-sterile soil treatments, indicating that soil microorganisms are associated with DEG remediation. These results demonstrated that plants and bacteria have the ability to form a relationship to remove the organic contaminant DEG. PMID- 21036474 TI - Microemulsion extraction separation and determination of aluminium species by spectrofluorimetry. AB - A simple and sensitive microemulsion extraction separation method was developed for the speciation of aluminium in tea samples by spectrofluorimetry. With 8 hydroxyquinoline (8-HQ) as the chelating agent and Triton X-100 Winsor II microemulsion as the extractant, separation of aluminium species in different pH solutions was achieved by microemulsion extraction. The formation of microemulsion, the conditions of extraction and determination of aluminium species were studied. The results showed that, the contents of aluminium species in tea leaves and infusions samples, such as total aluminium, total soluble aluminium, total granular aluminium, inorganic aluminium except Al-F, and (Al F+Al-org), were obtained successfully under the optimal conditions. The limit of detection was 0.23 MUg L(-1) in pH 9.5 solution, and 0.59 MUg L(-1) in pH 6.0 solution respectively; the precision (RSD) for 11 replicate measurements of 10 MUg L(-1) aluminium was 2.1% in pH 9.5 solution, and 2.8% in pH 6.0 solution respectively; the recoveries for the spiked samples were 96.8-103.5%. The proposed method is simple and efficient, which has been applied to the speciation of aluminium in tea samples with satisfactory results. PMID- 21036475 TI - Chronic treatment-related pain in cancer survivors. PMID- 21036477 TI - On the measurement of thickness in nanoporous materials by EELS. AB - This work discusses thickness measurements in nanoporous MgO using the log-ratio method in electron energy-loss spectroscopy (EELS). In heterogeneous nanoporous systems, the method can induce large errors if the strength of excitations at interfaces between pores and the matrix is large. In homogeneous nanoporous systems, on the other hand, the log-ratio method is still valid, but the inelastic scattering mean-free-path is no longer equal to that in the same bulk system. PMID- 21036476 TI - Tumor necrosis factor-alpha induces sensitization of meningeal nociceptors mediated via local COX and p38 MAP kinase actions. AB - The proinflammatory cytokine TNF-alpha has been shown to promote activation and sensitization of primary afferent nociceptors. The downstream signaling processes that play a role in promoting this neuronal response remain however controversial. Increased TNF-alpha plasma levels during migraine attacks suggest that local interaction between this cytokine and intracranial meningeal nociceptors plays a role in promoting the headache. Here, using in vivo single unit recording in the trigeminal ganglia of anesthetized rats, we show that meningeal TNF-alpha action promotes a delayed mechanical sensitization of meningeal nociceptors. Using immunohistochemistry, we provide evidence for non neuronal localization of the TNF receptors TNFR1 to dural endothelial vascular cells and TNFR2 to dural resident macrophages as well as to some CGRP-expressing dural nerve fibers. We also demonstrate that meningeal vascular TNFR1 is co localized with COX-1 while the perivascular TNFR2 is co-expressed with COX-2. We further report here for the first time that TNF-alpha evoked sensitization of meningeal nociceptors is dependent upon local action of cyclooxygenase (COX). Finally, we show that local application of TNF-alpha to the meninges evokes activation of the p38 MAP kinase in dural blood vessels that also express TNFR1 and that pharmacological blockade of p38 activation inhibits TNF-alpha evoked sensitization of meningeal nociceptors. Our study suggests that meningeal action of TNF-alpha could play an important role in the genesis of intracranial throbbing headaches such as migraine through a mechanism that involves at least part activation of non-neuronal TNFR1 and TNFR2 and downstream activation of meningeal non-neuronal COX and the p38 MAP kinase. PMID- 21036478 TI - Crystal structure solution via precession electron diffraction data: the BEA algorithm. AB - The statistical features of the amplitudes obtained via precession electron diffraction have been studied, with particular concern with their effects on direct phasing procedures. A new algorithm, denoted by BEA, is described: according to it, the average amplitude of the symmetry equivalent reflections is used in the Direct Methods step. Once an even imperfect structural model is available, the best amplitude among the equivalent reflections is used to improve the model. It is shown that BEA is able to provide more complete structural models, to make the phasing process more straightforward and to end with crystallographic residual much better than those usually obtained by electron diffraction. PMID- 21036479 TI - Intraspecific variability in several isolates of Philasterides dicentrarchi (syn. Miamiensis avidus), a scuticociliate parasite of farmed turbot. AB - Research on intraspecific variation in ciliates is scarce, and in scuticociliate parasite of fish, virtually nonexistent. In this study, seven isolates obtained from turbots affected by scuticociliatosis in different parts of the Iberian Peninsula (northwest Spain and southwest Portugal) were morphologically and genetically characterized to investigate the intraspecific divergence in these amphizoic ciliates. The isolates were stained with ammoniacal silver carbonate and examined in an optical microscope; all were found to have the typical morphological characteristics described for Philasterides dicentrarchi (syn. Miamiensis avidus). Sixteen biometric characteristics of the seven isolates were used in a canonical discrimination analysis (CDA) to select a subset of those that best identified each isolate. Discriminant analysis indicated that the OPK3 width, length of the PM2, length of the buccal field, the body width, L:W ratio, the body length, the OPK1 width and the distance between OPK2 and OPK3 were the most important morphological variables for discriminating the isolates. The first three canonical functions accounted for 86% of the total variance. The scatter plots of the first two canonical variables grouped and separated the P. dicentrarchi isolates into five clusters. Flow cytometry analysis of isolates also indicated intraspecific polymorphisms among P. dicentrarchi isolates. Nuclear markers (a 349-bp and a 390-bp fragment of 18S rRNA and beta-tubulin genes) and a 398-bp of the mitochondrial cytocrome oxidase subunit I (Cox1) gene were then used to investigate the intraspecific genetic variation in P. dicentrarchi. Haplotype analysis and neighbour-joining phylogenies of nucleotide sequences of seven isolates revealed a high degree of intraspecific genetic variation among the isolates. Analysis of Cox1 and beta-tubulin genes revealed six haplotypes (and clusters) in both cases; however, analysis of the 18S rRNA gene revealed only two haplotypes. The results show clear intraspecific variation at morphological and genetic levels in the scuticociliate P. dicentrarchi, and verify the suitability of mitochondrial (Cox1) and nuclear (beta-tubulin) genes for detecting intraspecific genetic variation within populations of scuticociliates that infect cultured turbot. The existence of this intraspecific variation must be taken into account in the design of an effective vaccine to control scuticociliatosis. PMID- 21036480 TI - Cloaca prolapse and cystitis in green iguana (Iguana iguana) caused by a novel Cryptosporidium species. AB - Cryptosporidium infection was associated with colitis and cystitis in 2 green iguanas (Iguana iguana). The disease was characterized by a chronic clinical course of cloacal prolapses and cystitis. Histological examination of the gut and urinary bladder showed numerous Cryptosporidium developmental stages on the surface of the epithelium with mixed inflammatory response in the lamina propria. Cryptosporidium oocysts were visualised in a cytological preparation of the faeces. Based on the small subunit ribosomal RNA gene the cryptosporidia were characterized as belonging to the intestinal cryptosporidial lineage, but not to Cryptosporidium saurophilum or Cryptosporidium serpentis species. PMID- 21036481 TI - Detection of Babesia and Theileria species infection in cattle from Portugal using a reverse line blotting method. AB - Babesiosis and Theileriosis are tick-borne diseases widespread in tropical and sub-tropical regions with high economic impact worldwide. In Portugal there are at least 4 tick vectors known to be competent for the transmission of Babesia and Theileria sp. identified: Rhipicephalus bursa, Rhipicephalus (Boophilus) annulatus, Ixodes ricinus and Haemaphysalis punctata. All these potential Babesia and Theileria tick vectors are widely distributed in Portugal, although they are predominant in the Southern region. In this study, 1104 cattle blood samples were randomly collected from Central and Southern regions of Portugal and analyzed by PCR-reverse line blotting (RLB) for the detection of Babesia and Theileria sp. Testing indicated that 74.7% of the bovines tested were positive for either Babesia and/or Theileria sp. In addition, five different apicomplexan species, namely, Theileria buffeli, Theileria annulata, Babesia divergens, Babesia bovis, and Babesia bigemina were detected by RLB among the bovines tested. T. buffeli was the most frequently found species, being present in 69.9% of the positive samples either as single infections (52.4%), or as mixed infections (17.5%). The Babesia specie most frequently found was B. divergens, detected in 4.2% of the infected bovines. Overall, infected bovines were found in all regions tested; however the highest number of infected bovines was observed in Evora district (96.2%) and in cattle from Limousin breeds (81.7%). The results indicate widespread Babesia and Theileria infections in Portuguese bovines, suggesting the need for improved control of ticks and tick-borne diseases. PMID- 21036482 TI - There may be a same mechanism of the left-right handedness and left-right convex curve pattern of adolescent idiopathic scoliosis. AB - The mechanism of the left-right handedness and pathogenesis of adolescent idiopathic scoliosis (AIS) is still unclear. We speculated that the pathogenesis of AIS may different from the mechanism of the laterality of convex curve pattern in AIS patients. This laterality may have correlation with the right dominance of handedness. The location and gravity of heart and aorta may determine the trend of lateral flexion and axial rotation of normal spine, which may be the reason of both left-right handedness and left-right convex curve pattern of AIS. PMID- 21036483 TI - Lactulose: an indirect antioxidant ameliorating inflammatory bowel disease by increasing hydrogen production. AB - Lactulose, which cannot be digested and absorbed by body, is clinically widely used to treat constipation and hepatic encephalopathy. Fermented by gastrointestinal tract bacteria, lactulose can produce considerable amount of hydrogen, which is protective for DSS-induced colitis as a unique antioxidant. We propose that lactulose is an indirect antioxidant that mobilizes endogenous hydrogen production which in turn can reduce oxidative stress and ameliorate symptoms of inflammatory bowel disease in human beings. PMID- 21036484 TI - Raman spectroscopic study of heat-induced gelation of pork myofibrillar proteins and its relationship with textural characteristic. AB - Structural changes, textural properties and their relationships in pork myofibrillar proteins (PMP) were studied by Raman spectroscopy, texture profile analysis (TPA) and principal component analysis (PCA). Raman spectroscopy analysis revealed the occurrence of secondary structural changes in myofibrillar proteins. Modifications in the amide I (1600-1700 cm(-1)) and amide III (1200 1300 cm(-1)) regions indicated a significant (p<0.05) decrease in alpha-helix content, accompanied by a significant (p<0.05) increase in beta-sheets, beta turns and random coil content. Texture property changes were also determined by TPA. All these features contributed to the formation of strong, irreversible heat induced gels. The application of a dimensionality reducing technique such as PCA proved to be useful to determine the most influential properties of heat-induced gel. Significant (p<0.05) correlations were found between these structural changes and the textural characteristic (hardness) in the pork myofibrillar proteins system by PCA. PMID- 21036485 TI - Characterization of loin shape from Duroc and Duroc composite finishing gilts. AB - Gilts (n=45) were used in this study to characterize the effect of genotype on loin characteristics and quality over the length of the loin. Three diverse genotypes included a high quality Duroc line (A), a Duroc based composite line selected for lean growth (B), and an F1 cross of the two (C). After harvest, bone in loins were removed from the carcass and cut perpendicular to the backbone at the 5th/6th rib, 7th/8th rib, 10th/11th rib, last rib, midlumbar, and the loin/sirloin juncture. Quality measurements were obtained at the 5th/6th rib, 10th/11th rib, and the loin/sirloin juncture. Digital images were taken of each surface (n=6) and analyzed for the determination of loin muscle area (LMA), muscle width, muscle depth (at three locations across the loin face), and fat depth. The average loin depth was calculated and used to calculate the loin depth:width ratio as an indication of loin shape or conformation. Loins from line A had the lowest (P<0.05) subjective color score, had the highest (P<0.05) amount of marbling, and were the firmest (P<0.05) of all three lines. There were also differences (P<0.05) between genetic lines for LMA, width, all three depths, fat depth, and depth:depth ratios. The most posterior portions of the loin had the largest (P<0.05) LMA, loin width, fat depth, and muscle depth 1. However, the more anterior portions of the loin had greater (P<0.01) values for the depth:width ratio and muscle depth:depth ratios. PMID- 21036486 TI - Long-term results of a prospective, Phase II study of long-term androgen ablation, pelvic radiotherapy, brachytherapy boost, and adjuvant docetaxel in patients with high-risk prostate cancer. AB - PURPOSE: We report the long-term results of a prospective, Phase II study of long term androgen deprivation (AD), pelvic radiotherapy (EBRT), permanent transperineal prostate brachytherapy boost (PB), and adjuvant docetaxel in patients with high-risk prostate cancer. METHODS AND MATERIALS: Eligibility included biopsy-proven prostate adenocarcinoma with the following: prostate specific antigen (PSA) > 20 ng/ml; or Gleason score of 7 and a PSA >10 ng/ml; or any Gleason score of 8 to 10; or stage T2b to T3 irrespective of Gleason score or PSA. Treatment consisted of 45 Gy of pelvic EBRT, followed 1 month later by PB with either iodine-125 or Pd-103. One month after PB, patients received three cycles of docetaxel chemotherapy (35 mg/m(2) per week, Days 1, 8, and 15 every 28 days). All patients received 2 years of AD. Biochemical failure was defined as per the Phoenix definition (PSA nadir + 2). RESULTS: From August 2000 to March 2004, 42 patients were enrolled. The median overall and active follow-ups were 5.6 years (range, 0.9-7.8 years) and 6.3 years (range, 4-7.8 years), respectively. Grade 2 and 3 acute genitourinary (GU) and gastrointestinal (GI) toxicities were 50.0% and 14.2%, respectively, with no Grade 4 toxicities noted. Grade 3 and 4 acute hematologic toxicities were 19% and 2.4%, respectively. Of the patients, 85.7% were able to complete the planned multimodality treatment. The 5- and 7-year actuarial freedom from biochemical failures rates were 89.6% and 86.5%, and corresponding rates for disease-free survival were 76.2% and 70.4%, respectively. The 5- and 7-year actuarial overall survival rates were 83.3% and 80.1%, respectively. The 5- and 7-year actuarial rates of late Grade 2 GI/GU toxicity (no Grade 3-5) was 7.7%. CONCLUSIONS: The trimodality approach of using 2 years of AD, external radiation, brachytherapy, and upfront docetaxel in high-risk prostate cancer is well tolerated, produces encouraging long-term results, and should be validated in a multi-institutional setting. PMID- 21036487 TI - Long-term follow-up of a prospective trial of trimodality therapy of weekly paclitaxel, radiation, and androgen deprivation in high-risk prostate cancer with or without prior prostatectomy. AB - PURPOSE: Weekly paclitaxel, concurrent radiation, and androgen deprivation (ADT) were evaluated in patients with high-risk prostate cancer (PC) with or without prior prostatectomy (RP). METHODS AND MATERIALS: Eligible post-RP patients included: pathological T3 disease, or rising prostate-specific antigen (PSA) >= 0.5 ng/mL post-RP. Eligible locally advanced PC (LAPC) patients included: 1) cT2b 4N0N+, M0; 2) Gleason score (GS) 8-10; 3) GS 7 + PSA 10-20 ng/mL; or 4) PSA 20 150 ng/mL. Treatment included ADT (4 or 24 months), weekly paclitaxel (40, 50, or 60 mg/m(2)/wk), and pelvic radiation therapy (total dose: RP = 64.8 Gy; LAPC = 70.2 Gy). RESULTS: Fifty-nine patients were enrolled (LAPC, n = 29; RP, n = 30; ADT 4 months, n = 29; 24 months, n = 30; whites n = 29, African Americans [AA], n = 28). Baseline characteristics (median [range]) were: age 67 (45-86 years), PSA 5.9 (0.1-92.1 ng/mL), GS 8 (6-9). At escalating doses of paclitaxel, 99%, 98%, and 95% of doses were given with radiation and ADT, respectively, with dose modifications required primarily in RP patients. No acute Grade 4 toxicities occurred. Grade 3 toxicities were diarrhea 15%, urinary urgency/incontinence 10%, tenesmus 5%, and leukopenia 3%. Median follow-up was 75.3 months (95% CI: 66.8 82.3). Biochemical progression occurred in 24 (41%) patients and clinical progression in 11 (19%) patients. The 5- and 7-year OS rates were 83% and 67%. There were no differences in OS between RP and LAPC, 4- and 24-month ADT, white and AA patient categories. CONCLUSIONS: In addition to LAPC, to our knowledge, this is the first study to evaluate concurrent chemoradiation with ADT in high risk RP patients. With a median follow-up of 75.3 months, this trial also represents the longest follow-up of patients treated with taxane-based chemotherapy with EBRT in high-risk prostate cancer. Concurrent ADT, radiation, and weekly paclitaxel at 40 mg/m(2)/week in RP patients and 60 mg/m(2)/week in LAPC patients is feasible and well-tolerated. PMID- 21036488 TI - Lessons from a 17-year radiosurgery experience at the Royal Adelaide Hospital. AB - PURPOSE: To illustrate some of the potential pitfalls of cranial stereotactic radiosurgery (SRS) and its planning based on prospectively gathered data from a 17-year experience at the Royal Adelaide Hospital. METHODS AND MATERIALS: More than 250 treatments have been planned since 1993 using previously described standard SRS techniques for intracranial benign and malignant lesions. RESULTS: Five case studies are presented (1 meningioma, 1 acoustic neuroma, 2 solitary brain metastasis, 1 arteriovenous malformation), each of which demonstrates at least one salutary lesson. CONCLUSIONS: Because SRS delivers a highly conformal dose distribution, it is unforgiving of any geographic miss due to inaccurate outlining and thus dependent on neuroradiological expertise and collaboration. There are also potentially significant implications of misdiagnosis in SRS cases without histological proof--in particular, presumed brain metastases. PMID- 21036489 TI - Forward intensity-modulated radiotherapy planning in breast cancer to improve dose homogeneity: feasibility of class solutions. AB - PURPOSE: To explore forward planning methods for breast cancer treatment to obtain homogeneous dose distributions (using International Commission on Radiation Units and Measurements criteria) within normal tissue constraints and to determine the feasibility of class solutions. METHODS AND MATERIALS: Treatment plans were optimized in a stepwise procedure for 60 patients referred for postlumpectomy irradiation using strict dose constraints: planning target volume (PTV)(95%) of >99%; V(107%) of <1.8 cc; heart V(5 Gy) of <10% and V(10 Gy) of <5%; and mean lung dose of <7 Gy. Treatment planning started with classic tangential beams. Optimization was done by adding a maximum of four segments before adding beams, in a second step. A breath-hold technique was used for heart sparing if necessary. RESULTS: Dose constraints were met for all 60 patients. The classic tangential beam setup was not sufficient for any of the patients; in one third of patients, additional segments were required (<3), and in two-thirds of patients, additional beams (<2) were required. Logistic regression analyses revealed central breast diameter (CD) and central lung distance as independent predictors for transition from additional segments to additional beams, with a CD cut-off point at 23.6 cm. CONCLUSIONS: Treatment plans fulfilling strict dose homogeneity criteria and normal tissue constraints could be obtained for all patients by stepwise dose intensity modification using limited numbers of segments and additional beams. In patients with a CD of >23.6 cm, additional beams were always required. PMID- 21036490 TI - Addition of bevacizumab to standard radiation therapy and daily temozolomide is associated with minimal toxicity in newly diagnosed glioblastoma multiforme. AB - PURPOSE: To determine the safety of the addition of bevacizumab to standard radiation therapy and daily temozolomide for newly diagnosed glioblastoma multiforme (GBM). METHODS AND MATERIALS: A total of 125 patients with newly diagnosed GBM were enrolled in the study, and received standard radiation therapy and daily temozolomide. All patients underwent a craniotomy and were at least 2 weeks postoperative. Radiation therapy was administered in 1.8-Gy fractions, with the clinical target volume for the primary course treated to a dose of 45 to 50.4 Gy, followed by a boost of 9 to 14.4 Gy, to a total dose of 59.4 Gy. Patients received temozolomide at 75 mg/m(2) daily throughout the course of radiation therapy. Bevacizumab was given at 10 mg/kg intravenously every 14 days, beginning a minimum of 4 weeks postoperatively. RESULTS: Of the 125 patients, 120 (96%) completed the protocol-specified radiation therapy. Five patients had to stop the protocol therapy, 2 patients with pulmonary emboli, and 1 patient each with a Grade 2 central nervous system hemorrhage, Grade 4 pancytopenia, and wound dehiscence requiring surgical intervention. All 5 patients ultimately finished the radiation therapy. After radiation therapy, 3 patients had progressive disease, 2 had severe fatigue and decreased performance status, 1 patient had a colonic perforation, and 1 had a rectal fissure; these 7 patients therefore did not proceed with the protocol-specified adjuvant temozolomide, bevacizumab, and irinotecan. However, 113 patients (90%) were able to continue on study. CONCLUSIONS: The addition of bevacizumab to standard radiation therapy and daily temozolomide was found to be associated with minimal toxicity in patients newly diagnosed with GBM. PMID- 21036491 TI - [Functional results following transobturator and retropubic mid-urethral sling]. AB - OBJECTIVE: To compare functional results following retropubic and transobturator mid-urethral sling procedures. METHODS: Multicenter randomized controlled trial. Power calculation was based on the rate of bladder injury. The current study concerns an analysis of secondary judgment criteria. RESULTS: One hundred and forty-nine patients were randomly allocated to either TVT (n=75) or TVT-O (n=74). Among them, 132 women completed a 24-month follow-up. There was no significant difference between the two groups, concerning urodynamics data (excluding uroflowmetry) at 12 months follow-up, functional and sexual results at 6, 12 and 24 months follow-up. Concerning sexual results, an improvement in visual analogue scale scores was observed in both groups at 24 months follow-up with no difference between the two groups: median score increased from 70 (IQR: 50-80) pre-operatively to 90 (IQR: 70-100) at 24 months follow-up (P=0,0004) in TVT-O group and from 70 (IQR: 50-80) to 85 (IQR: 70-100) (P=0,0009) in TVT group. CONCLUSION: TVT and TVT-O procedures are both associated with an increase in quality of life with no significant differences in functional results at 2 years follow-up. PMID- 21036492 TI - Nicotine dependence as a moderator of a quitline-based message framing intervention. AB - High nicotine dependence is a reliable predictor of difficulty quitting smoking and remaining smoke-free. Evidence also suggests that the effectiveness of various smoking cessation treatments may vary by nicotine dependence level. Nicotine dependence, as assessed by Heaviness of Smoking Index baseline total scores, was evaluated as a potential moderator of a message-framing intervention provided through the New York State Smokers' Quitline (free telephone based service). Smokers were exposed to either gain-framed (n=810) or standard-care (n=1222) counseling and printed materials. Those smoking 10 or more cigarettes per day and medically eligible were also offered a free 2-week supply of nicotine patches, gum, or lozenge. Smokers were contacted for follow-up interviews at 3 months by an independent survey group. There was no interaction of nicotine dependence scores and message condition on the likelihood of achieving 7-day point prevalence smoking abstinence at the 3-month follow-up contact. Among continuing smokers at the 3-month follow-up, smokers who reported higher nicotine dependence scores were more likely to report smoking more cigarettes per day and this effect was greater in response to standard-care messages than gain-framed messages. Smokers with higher dependence scores who received standard-care messages also were less likely to report use of nicotine medications compared with less dependent smokers, while there was no difference in those who received gain-framed messages. These findings lend support to prior research demonstrating nicotine dependence heterogeneity in response to message framing interventions and suggest that gain-framed messages may result in less variable smoking outcomes than standard-care messages. PMID- 21036493 TI - The major surface Vsp proteins of Brachyspira hyodysenteriae form antigenic protein complexes. AB - The Vsp proteins are the major outer membrane proteins of Brachyspira hyodysenteriae, the causative agent of swine dysentery. Eight vsp genes have been identified in B. hyodysenteriae strain B204, arranged into two four-gene loci, and at least two of the corresponding proteins are produced in vitro. The aims of this study were to characterise the vsp genes of the virulent Australian B. hyodysenteriae strain X576 and their corresponding proteins, Genomic sequence comparison with strains B204 and WA1 demonstrated that the number of vsp genes varies between B. hyodysenteriae strains, although the chromosomal locations of the vsp gene loci are consistent. We identified two additional vsp-like genes, designated vspI and vspJ, in each of the three strains. Double SDS-PAGE was used to demonstrate that Vsp proteins of B. hyodysenteriae strain X576 form multimeric protein complexes in the outer membrane that are stable in 6M urea but dissociate after boiling. The Vsp complexes primarily consisted of VspF but also contain VspE and VspI. VspD was also found in a series of complexes slightly larger than the more abundant VspF complexes. Vsp proteins are purported to be antigenic; however little direct data are available to support this claim. In this study convalescent pig sera did not bind denatured Vsp proteins by Western blotting, but did bind the Vsp complexes on Western blots, showing that conformational epitopes may be important in immune recognition of these major outer membrane proteins. This is the first definitive demonstration of the antigenicity of these proteins in swine dysentery. PMID- 21036494 TI - Are bacterial load and synovitis related in dogs with inflammatory stifle arthritis? AB - It has been proposed that small quantities of microbial material within synovial joints may act as a trigger for development of synovitis. We have previously identified an association between intra-articular bacteria and development of inflammatory stifle arthritis and cranial cruciate ligament rupture (CCLR) in dogs, and now wished to quantify bacterial load and markers of synovitis in dogs with and without stifle arthritis and CCLR. Joint tissues were collected from dogs with CCLR (n=51) and healthy dogs with normal stifles (n=9). Arthritis was assessed radiographically in CCLR dogs. Bacterial load was assessed using qPCR and broad-ranging 16S rRNA primers. qRT-PCR was used to estimate expression of the T lymphocyte antigen receptor (TCR Vbeta), CD3E, tartrate-resistant acid phosphatase (TRAP), IL-4, IL-17, and TNF-alpha genes. Severity of synovitis was assessed histologically. Bacterial load was increased in arthritic stifles, when compared with healthy stifles. Histologic synovitis in arthritic stifles was mononuclear and was significantly correlated with bacterial load (1 of 2 primer sets) (S(R)=0.49, p<0.001). In arthritic stifles, expression of TRAP in synovium was increased relative to healthy stifles. Expression of pro-inflammatory genes was not correlated with bacterial load, histologic inflammation, or radiographic arthritis. Translocation of bacterial material to the canine stifle is related to the presence of joint inflammation. The lack of a strong positive correlation suggests that bacterial load is unlikely to be a primary pro-inflammatory factor. However, dysregulation of immune responses within synovial tissues may be dependent upon an environmental microbial trigger. PMID- 21036495 TI - Fatal poisoning in drug addicts in the Nordic countries in 2007. AB - The frequency of medico-legally examined fatal poisonings in 2007 among drug addicts was investigated in five Nordic countries; Denmark, Finland, Iceland, Norway, and Sweden. The number of deaths, age, sex, place of death, main intoxicant, and other drugs present in blood samples were recorded to obtain national and comparable Nordic data, as well as data to compare with earlier studies in 2002, 1997, and 1991. Norway had the highest incidence of drug addict deaths by poisoning followed by Denmark, with 8.24 and 6.92 per 100,000 inhabitants, respectively. The death rates in Finland (4.02), Iceland (4.56), and Sweden (3.53) were about half that of Norway and Denmark. Compared with earlier studies, the death rates were unchanged in Denmark and Norway, but increased in Finland, Iceland, and Sweden. In all countries, fewer deaths (29-35%) were recorded in the capital area compared with earlier studies. Females accounted for 11-19% of the fatal poisonings. Iceland deviates with a more equal distribution between men and women (40%). Deaths from methadone overdoses increased in all Nordic countries, and methadone was the main intoxicant in Denmark in 2007, accounting for 51% of the poisonings. In Norway and Sweden, heroin/morphine was still the main intoxicant with a frequency of 68% and 48%, respectively. In Iceland, 3 deaths each were due to heroin/morphine and methadone, respectively. Finland differs from other Nordic countries in having a high number of poisonings caused by buprenorphine and very few caused by heroin/morphine. The total number of buprenorphine deaths in Finland doubled from 16 in 2002 to 32 in 2007, where it constituted 25% of deaths. The general toxicological screening program showed widespread multi-drug use in all countries. The median number of drugs per case varied from 3 to 5. The most frequently detected substances were heroin/morphine, methadone, buprenorphine, tramadol, amphetamine, cocaine, tetrahydrocannabinol, benzodiazepines and ethanol. PMID- 21036496 TI - Differentiation of drug and non-drug Cannabis using a single nucleotide polymorphism (SNP) assay. AB - Cannabis sativa is both an illegal drug and a legitimate crop. The differentiation of illegal drug Cannabis from non-drug forms of Cannabis is relevant in the context of the growth of fibre and seed oil varieties of Cannabis for commercial purposes. This differentiation is currently determined based on the levels of tetrahydrocannabinol (THC) in adult plants. DNA based methods have the potential to assay Cannabis material unsuitable for analysis using conventional means including seeds, pollen and severely degraded material. The purpose of this research was to develop a single nucleotide polymorphism (SNP) assay for the differentiation of "drug" and "non-drug"Cannabis plants. An assay was developed based on four polymorphisms within a 399 bp fragment of the tetrahydrocannabinolic acid (THCA) synthase gene, utilising the snapshot multiplex kit. This SNP assay was tested on 94 Cannabis plants, which included 10 blind samples, and was able to differentiate between "drug" and "non drug"Cannabis in all cases, while also differentiating between Cannabis and other species. Non-drug plants were found to be homozygous at the four sites assayed while drug Cannabis plants were either homozygous or heterozygous. PMID- 21036497 TI - Prognostic factors in oral cavity cancer with skull base recurrence. AB - OBJECTIVE: Recurred oral cavity cancer at the skull base is complicated to treat due to difficult surgical approach and possible dural invasion. Therefore, initial curative treatment is of most importance and it would be helpful to know cases that would likely recur before treatment. We tried to identify prognostic factors that can predict skull base recurrence after initial treatment, to find out cases that need more aggressive initial treatment. METHODS: This retrospective study was performed on 51 patients diagnosed as squamous cell carcinoma in the oral cavity, and they underwent surgery and adjuvant radiotherapy. Variables associated with clinical findings, imaging studies, and pathologic results were analyzed to identify factors related to skull base recurrence. RESULTS: Recurrences occurred in 21% (11) cases, and skull base invasion in 5 of these recurred cases. Tumor location, clinical T stage, retromolar trigone (RMT) invasion, bone invasion, perineural invasion, positive resection margin, endolymphatic tumor emboli, and medial and lateral pterygoid muscle invasion were found to be significant prognostic factors by univariate analyses. Among those factors, medial pterygoid muscle invasion and positive resection margin remained independent predictors of skull base recurrence with multivariate analyses by Cox regression. CONCLUSION: Patients with medial pterygoid muscle invasion or a positive resection margin have a high risk of skull base invasion during tumor recurrence. Therefore, careful evaluation and aggressive management are needed to prevent skull base invasion in cases that recur. PMID- 21036498 TI - Eustachian tube function in patients with Meniere's disease. AB - OBJECTIVE: The aim of the present study was to clarify the relationship between Eustachian tube function and inner ear function, especially with respect to the hearing ability of patients with Meniere's disease. METHODS: Patients with Meniere's disease underwent nystagmic examinations and audiometric measurements, including hearing tests, tympanometry, and Eustachian tube function tests (sonotubometry). We compared the audiometric examination results of normal subjects to those of patients with Meniere's disease. RESULTS: Twenty-five percent of patients with Meniere's disease exhibited Eustachian tube dysfunction, but 92% displayed normal tympanometry findings. Their sonotubometry durations and amplitudes were not significantly different from those of normal subjects. However, the patients' hearing level was significantly correlated to sonotubometry duration and amplitude. Our patients were classified according to the four stages of Meniere's disease: stage 1 (n=9); stage 2 (n=5); stage 3 (n=8); and stage 4 (n=2). The incidence of Eustachian tube dysfunction in these four groups of patients were 0% (0/9); 40% (2/5); 38% (3/8); and 50% (1/2), respectively. CONCLUSION: Our study provides evidence demonstrating that treatment of Eustachian tube dysfunction may be useful in preventing the hearing of Meniere's patients from becoming worse. PMID- 21036499 TI - Pitfalls in diagnosing psychogenic nonepileptic seizures in a sexually abused child. AB - A six-year-old girl living in a residential care facility because of previous sexual abuse at home showed intractable seizures with epileptic discharges on interictal EEG. The features of the attacks were sudden impaired consciousness, only in daytime while eating, studying, and walking, with no motor acts and continuing for several minutes to one hour. She could not recall the attacks, and anticonvulsants showed no effects. She gradually became irritated and antisocial, exhibiting impulsive and hyperactive behavior. Interictal EEG repeatedly showed diffuse irregular spikes and wave complexes. The attacks continued sporadically for more than two years and ceased after disclosure of repeated sexual abuse by a boy at the residential care facility. In this case, delayed diagnosis of psychogenic nonepileptic seizures was associated with diagnostic difficulty of dissociative symptoms in a child, the presence of epileptiform EEG in an abused child, and undetected sexual abuse in a residential care facility, the potential for which pediatric neurologists should be aware. These pitfalls are discussed in the context of previous related literature. PMID- 21036500 TI - Image of the month. Hepatic visceral larva migrans due to Toxocara Canis. PMID- 21036501 TI - Results of a national survey on quality of life in inflammatory bowel diseases. AB - AIMS: Inflammatory bowel diseases (IBD) have a negative impact on patients' quality of life. The aims of this survey were to learn more about patients' concerns, and to compare their feelings with the beliefs of their close relations and physicians. PATIENTS AND METHODS: A specific questionnaire, including the RFIPC and the MFI-20, was used. Patients' answers were compared with those given by their close relations and attending physicians. RESULTS: This national survey included 2424 French patients. At the time of diagnosis, 73% of patients expressed having fears, but were also relieved to understand their symptoms. IBD was responsible for fatigue and weariness, and had a negative impact on daily, occupational, leisure, family and personal life. The main fears concerned unpredictable flare-ups followed by need for an ostomy bag and risk of surgery. The answers provided by close relations and physicians matched those of the patients, but physicians overestimated the patient's knowledge and underestimated disease impact. CONCLUSION: IBD has a deleterious effect on quality of life. Close relations of the patient realize the impact the disease has on the patients' life, but attending physicians still tend to minimize patients' symptoms. PMID- 21036502 TI - Composition of a volatile extract of Eryngium duriaei subsp. juresianum (M. Lainz) M. Lainz, signalised by the antifungal activity. AB - The composition of a volatile extract of Eryngium duriaei subsp. juresianum, signalised by the antifungal activity (MIC values=0.16-0.32 MUL mL(-1)) against several dermatophyte species (Trichophyton mentagrophytes, T. rubrum, Epidermophyton floccosum; T. verrucosum, T. mentagrophytes var interdigitale, Microsporum canis and M. gypseum) was established following a combined methodology of GC, GC-MS and an exclusive (13)C NMR technique that does not require prior isolation of compounds. Twenty-five components were identified accounting 84.6% of the whole composition. Major compound was found to be alpha neocallitropsene (26.0%) although the dominance of caryophyllane derived compounds, the most probable responsible for the antifungal activity, namely isocaryophyllen-14-al (16.2%), 14-hidroxy-beta-caryophyllene (13.4%), caryophyllene oxide (7.6%) and E-beta-caryophyllene (6.3%). PMID- 21036503 TI - Chiral separation of potent corticotropin-releasing factor-1 receptor antagonists by supercritical fluid chromatography. AB - Pyrazinones bearing an N-1-alkyl chain with a chiral center have been reported as potent antagonists of the corticotropin-releasing factor-1 receptor (CRF1R). Separation of individual enantiomers for preclinical testing was an important aspect of lead optimization. To evaluate the applicability and efficiency of supercritical fluid chromatography (SFC) for enantiomeric resolution of this class of compounds, enantiomeric pairs of eight pyrazinones with different structural characteristics were tested under an array of SFC conditions. The results showed that pyrazinones with a 1-cyclopropyl-2-methoxyethyl substituent were readily separated with a Chiralpak AD-H or Chiralcel OD-H column with ethanol as the modifier. On the other hand, analogs with a less polar alkyl substituent were not amenable to the general method and required further optimization of the chromatographic conditions. In addition, structural variations on the pyrazinone core and aromatic moiety had an impact on the chiral resolution of this class of compounds. This investigation led to the development of efficient chiral SFC methods for separating all eight pyrazinone enantiomeric pairs encompassing an array of structural variations. PMID- 21036504 TI - Rapidly onset rectus sheath hematoma mimicking cholecystitis. PMID- 21036505 TI - Development of a taxonomy of interventions to organise the evidence on consumers' medicines use. AB - OBJECTIVE: Safe, effective (quality) medicines use remains problematic worldwide, yet consumers' medicines use research is not well organised. This creates difficulties for decision makers in identifying evidence or research gaps and in understanding how or why interventions work. Developing a conceptual framework for this evidence helps to organise the evidence for application and raise awareness of the range of possible interventions. METHODS: To scope the aims of interventions to improve consumers' medicines use we searched for and iteratively analysed policy documents, systematic reviews, and an existing consumer-oriented communication intervention taxonomy. RESULTS: We identified eight recurrent themes associated with the purpose of the interventions: to inform and educate; to support behaviour change; to teach skills; to facilitate communication and/or decision making; to support; to minimise risk and harms; to involve consumers at the system level; and to improve health care quality. CONCLUSION: The taxonomy accommodates the complexity and diversity of interventions in this field, by focussing on the purposes of interventions, rather than the intervention type. PRACTICE IMPLICATIONS: Currently used to organise the evidence on consumers' medicines use, the taxonomy provides a conceptual and practical map of the evidence which will aid decision making and future research investment in the area. PMID- 21036506 TI - Infertility; isolation and the Internet: a qualitative interview study. AB - OBJECTIVES: This study explores the roles and meanings of the Internet, which is commonly used in this age group, as a source of support for people with fertility problems. METHODS: A qualitative interview study with 27 women and 11 men who had been, or were going, through treatment for infertility. A maximum variation sample was sought. Narrative interviews were conducted and transcribed for thematic analysis. RESULTS: Women and men with fertility problems often feel isolated. The Internet offers anonymity, emotional support, normalisation and reassurance. It also offers the prospect of niche support from others going through treatments at the same time and in similar circumstances. Online infertility networks can play a valuable role in helping people deal with the emotional stresses and isolation they feel during and after treatment, but has the potential to reinforce isolation. CONCLUSIONS: The Internet is changing people's experience of infertility, giving people access to other's experiences. Internet communication is highly valued by couples, especially those isolated in their real world relationships. PRACTICE IMPLICATIONS: Clinicians can help by referring couples to websites while being aware that increasingly 'niche' support could compound isolation. PMID- 21036507 TI - Knowledge, attitudes, and practice on second primary cancer screening among cancer survivors: a qualitative study. AB - OBJECTIVE: The goal of this study was to examine the knowledge, attitude, and practice on second cancer screening among cancer survivors. METHODS: Three focus group interviews were conducted with thirteen disease-free stomach, colorectal, breast and thyroid cancer survivors. Recurrent issues were identified and then placed into thematic categories. RESULTS: None of the study participants had heard SPC, and they could not differentiate SPC from 'recurrence' or 'metastasis.' Survivors believed that they had been cured, and they were not aware of their increased risk of SPC. Although they had high awareness of cancer screening, they could not make a distinction between 'cancer screening' and 'routine surveillance test' after cancer treatment. Survivors said that they would have had the screening for SPC if they had known about it. They preferred physicians as the most reliable source for screening information. CONCLUSION: Cancer survivors had limited knowledge about SPC, and lack of information was the main barrier for SPC screening. PRACTICE IMPLICATIONS: An educational intervention would help cancer survivors to understand their risk of SPC and the needs of screening after the first cancer. PMID- 21036508 TI - Efficacy of indirect dopamine agonists for psychostimulant dependence: a systematic review and meta-analysis of randomized controlled trials. AB - Psychostimulant dependence is characterized by dopamine deficit, which could be reversed with indirect dopamine agonists (IDAs). A systematic review and meta analysis of randomized, parallel-group, placebo-controlled clinical trials assessing the efficacy of IDAs in psychostimulant-dependent individuals were conducted. The study outcomes were psychostimulant abstinence, assessed by means of urinalysis, and retention in treatment. Risk of bias was determined using a Cochrane Collaboration instrument. Twenty-nine studies fulfilled the inclusion criteria, involving 2,467 participants. Compared with placebo, IDAs increased psychostimulant abstinence (standardized mean difference = 0.20; 95% confidence interval, 0.06-0.35; p = .005) but did not increase retention in treatment. Efficacy was larger in comorbid heroin-dependent individuals and was positively related with treatment length. No study was considered fully free of bias. IDAs appear to be efficacious for reducing psychostimulant use but did not improve retention. Efforts should be undertaken to reduce the risk of bias of clinical trials with psychostimulant-dependent individuals. PMID- 21036509 TI - Adapting problem-solving therapy for depressed older adults in methadone maintenance treatment. AB - Late-life depression is prevalent in older adults who are dependent on opiates. Depressive disorders among opiate abusers have detrimental effects on their well being and ability to refrain from illegal drugs. There are numerous barriers to the provision of appropriate mental health care to older adults receiving methadone maintenance treatment. This article focuses on problem-solving therapy (PST) and presents evidence that PST may be a promising nonpharmacological treatment for older methadone clients with comorbid depressive disorders that can be applied within the staffing and resource limits of methadone maintenance treatment facilities. The advantages of PST relative to other behavioral therapies for this population are based on evidence that PST is less cognitively demanding for an older adult population with mood and substance use disorders. A properly modified PST for an older adult substance-dependent population with subsyndromal or diagnosed depression may be a viable option for methadone maintenance programs with limited resources. PMID- 21036511 TI - WITHDRAWN: Comparing mental health and addiction characteristics of lesbian/gay/bisexual/transgender/transsexual/queer and non lesbian/gay/bisexual/transgender/transsexual/queer clients in a residential treatment setting. PMID- 21036510 TI - Characteristics and 9-month outcomes of discharged methadone maintenance clients. AB - This study is a secondary data analysis of a clinical trial assessing the effectiveness of outreach case management (OCM) in linking discharged methadone patients back into treatment. The original trial assessed the effectiveness of the OCM intervention compared to a passive referral among methadone clients who needed treatment postdischarge but had not reengaged. The purpose of this study was to assess the characteristics and long-term outcomes of all clients who were discharged from methadone maintenance treatment including those who had reengaged in treatment. A total of 230 methadone clients were interviewed 3 months and then again at 9 months following discharge from treatment. Compared with participants who needed treatment but had not reengaged (NoTx: 56%), those who had successfully reenrolled in treatment (Tx; 44%) were more likely to be female, not married, and unemployed; had a longer history of sedative use; reported more psychiatric hospitalizations; and were originally enrolled in a community-based rather than a Veterans Administration program. Despite having more severe problems, the Tx group had fewer opioid-positive urines and reported less IV drug use at 9 months postdischarge compared to the NoTx group. The findings highlight the importance of rapid treatment reengagement. PMID- 21036512 TI - Unintended pregnancy in opioid-abusing women. AB - The aim of this study was to estimate the prevalence of unintended pregnancy and its three subtypes (mistimed, unwanted, and ambivalent) among opioid-abusing women. In the general population, 31%-47% of pregnancies are unintended; data on unintended pregnancy in opioid- and other drug-abusing women are lacking. Pregnant opioid-abusing women (N = 946) screened for possible enrollment in a multisite randomized controlled trial comparing opioid maintenance medications completed a standardized interview assessing sociodemographic characteristics, current and past drug use, and pregnancy intention. Almost 9 of every 10 pregnancies were unintended (86%), with comparable percentages mistimed (34%), unwanted (27%), and ambivalent (26%). Irrespective of pregnancy intention, more than 90% of the total sample had a history of drug abuse treatment, averaging more than three treatment episodes. Interventions are sorely needed to address the extremely high rate of unintended pregnancy among opioid-abusing women. Drug treatment programs are likely to be an important setting for such interventions. PMID- 21036513 TI - Workforce professionalism in drug treatment services: impact of California's Proposition 36. AB - This article investigates whether California's Proposition 36 has promoted the workforce professionalism of drug treatment services during its first 5 years of implementation. Program surveys inquiring about organizational information, Proposition 36 implementation, and staffing were conducted in 2003 and 2005 among all treatment providers serving Proposition 36 clients in five selected California counties (San Diego, Riverside, Kern, Sacramento, and San Francisco). A 1-hour self-administered questionnaire was completed by 118 treatment providers representing 102 programs. This article examines five topics that are relevant to drug treatment workforce professionalism: resources and capability, standardized intake assessment and outcome evaluation, staff qualification, program accreditation, and information technology. Results suggest that Proposition 36 had a positive influence on the drug treatment workforce's professionalism. Improvements have been observed in program resources, client intake assessment and outcome evaluation databases, staff professionalization, program accreditation, and information technology system. However, some areas remain problematic, including, for example, the consistent lack of adequate resources serving women with children. PMID- 21036514 TI - Outpatient versus inpatient opioid detoxification: a randomized controlled trial. AB - Opioid detoxification is not an effective stand-alone treatment for heroin dependence but is nevertheless an essential step in the path to recovery. There has been relatively little previous controlled research on the impact of treatment setting on the likelihood of successful completion of detoxification. In this study, 68 opioid-dependent patients receiving community treatment (predominantly with methadone) and requesting detoxification were randomly assigned to an inpatient versus outpatient setting. Both groups received the same medication (lofexidine), and the primary outcome measure was being opioid-free at detoxification completion. More inpatients (n = 18, 51.4%) than outpatients (n = 12, 36.4%) completed detoxification, but this difference was not statistically significant (chi(2) = 1.56, p = .21). However, the outpatient group received a significantly longer period of medication, and when the length of detoxification was controlled for, the results favored the inpatient setting (Exp(B) = 13.9, 95% confidence interval = 2.6-75.5, p = .002). Only 11 (16%) participants were opioid free at the 1-month follow-up and 8 at the 6-month follow-up, with no between group difference. Inpatient and outpatient opioid detoxification settings were not significantly different in completion or follow-up abstinence rates, but aspects of the study design may have favored the outpatient setting. Future studies should test patient characteristics that predict better outcomes in each setting. PMID- 21036515 TI - Alcohol use problem among patients in methadone maintenance treatment in Taiwan. AB - AIMS: To examine the prevalence rate and predictors of alcohol use problems among patients undergoing methadone maintenance treatment (MMT). DESIGN: This was a prospective follow-up study. PARTICIPANTS: Study population included 438 patients who underwent more than 6 months of MMT. MEASUREMENTS: Demographic and clinical characteristics were collected for each patient prior to treatment, and treatment related variables were collected during treatment process. Hazardous drinking, alcohol abuse, and dependence were measured using a Chinese version of the Alcohol Use Disorders Identification Test (AUDIT) and by measuring breath alcohol concentration. FINDINGS: The prevalence rates of alcohol use problems, indicated by hazardous drinking are 31.4%. The protective predictors of alcohol use problems among MMT patients include an attendance rate of more than 90% (odds ratio [OR] = 0.54, 95% confidence interval [CI] = 0.30-0.97) and being older than 36 years (OR = 0.48, 95% CI = 0.27-0.86), and alcohol drinking problem at intake of study is a risk factor (OR = 5.30, 95% CI = 2.87-9.76). CONCLUSIONS: High attendance rate, which is regarded as a component of clinical policy and a key component of therapeutic context, should be incorporated with brief interventions to lower alcohol use problems among MMT patients. PMID- 21036516 TI - Predictors of addiction treatment providers' beliefs in the disease and choice models of addiction. AB - Addiction treatment providers working in the United States (n = 219) and the United Kingdom (n = 372) were surveyed about their beliefs in the disease and choice models of addiction, as assessed by the 18-item Addiction Belief Scale of J. Schaler (1992). Factor analysis of item scores revealed a three-factor structure, labeled "addiction is a disease," "addiction is a choice," and "addiction is a way of coping with life," and factor scores were analyzed in separate hierarchical multiple regression analyses. Controlling for demographic and addiction history variables, treatment providers working in the United States more strongly believe addiction is a disease, whereas U.K.-based providers more strongly believe that addiction is a choice and a way of coping with life. Beliefs that addiction is a disease were stronger among those who provide for profit treatment, have stronger spiritual beliefs, have had a past addiction problem, are older, are members of a group of addiction professionals, and have been treating addiction longer. Conversely, those who viewed addiction as a choice were more likely to provide public/not-for-profit treatment, be younger, not belong to a group of addiction professionals, and have weaker spiritual beliefs. Additionally, treatment providers who have had a personal addiction problem in the past were significantly more likely to believe addiction is a disease the longer they attend a 12-step-based group and if they are presently abstinent. PMID- 21036517 TI - The process of tendon regeneration in an achilles tendon resection rat model as a model for hamstring regeneration after harvesting for anterior cruciate ligament reconstruction. AB - PURPOSE: The purpose of this study was to clarify the mechanism of tendon regeneration by investigating macroscopically, histologically, and biomechanically. METHODS: Fifty, adult, female Sprague-Dawley rats were used. The Achilles tendon in the left hind limb was removed totally by use of the tendon stripping device. Rats were killed at 2, 7, 30, 90, and 180 days after surgery, and the regenerate tendons were dissected. Contralateral Achilles tendons were used as normal controls. Gross anatomic changes, microscopic remodeling, and recovery of biomechanical properties of regenerate tendons were investigated. The expressions of type I collagen, type III collagen, and transforming growth factor beta1 were also investigated by immunohistochemistry. RESULTS: The regenerate tendons formed in all specimens. In the early phase, hematoma and soft granulation tissue were observed at the harvest defect. These gradually matured with time, and the microscopic structure became quite similar to normal at 180 days after surgery. These findings occurred uniformly along the entire length of the regenerate tendon. However, the biomechanical properties were significantly inferior to the normal tendons (P < .05). Transforming growth factor beta1 was well co-localized with inflammatory cells and fibroblasts in the regenerate tendons. The type I-type III collagen ratio in the regenerate tendon was significantly decreased in the early phase (P < .05) but gradually increased with time. CONCLUSIONS: Tendon regeneration and maturation occurred uniformly along the length of regenerate tendons. The hematoma that initially occupies the harvest defect acted as a scaffold for fibroblast precursor cells from the surrounding peritendinous tissue and tendon sheath. The mechanical properties of regenerate tendon were significantly inferior to contralateral control even at 180 days after surgery, and the alteration of the collagen composition would have an influence on mechanical properties of regenerate tendon. CLINICAL RELEVANCE: Clinicians should be cautious about using reharvested hamstring tendons for ligament reconstruction surgery. PMID- 21036518 TI - Functional expression of chimeric Fab of an anti-CD40L mAb: Vector design and culture condition optimization. AB - CD40L is an important costimulatory molecule in the induction of the humoral and cell-mediated immune responses. 4F1, a specific murine antagonistic monoclonal antibody against human CD40L molecule, is a promising candidate biomedicine for autoimmune diseases, transplantation rejection and anti-angiogenesis therapy of cancer. To avoid the mAb induced thromboembolism as a consequence of platelet surface FcgammaR activation, we attempted to construct a chimeric Fab of 4F1 to minimize its side effects for potential clinical use. A chimeric version of anti CD40L Fab was generated by transferring mouse variable regions into a human framework. Our study indicated that 4F1 could be simply and rapidly converted to chimeric Fab which could be expressed in bacteria and purified in reasonable quantities. This chimeric antibody maintained its bioreactivity to human CD40L. PMID- 21036519 TI - [Digestive Kaposi disease among HIV-positive patients in Africa]. PMID- 21036520 TI - [Pasteurella multocida meningoencephalitis]. PMID- 21036521 TI - Bacteremia in Staphylococcus aureus pneumonia: outcomes and epidemiology. AB - PURPOSE: Staphylococcus aureus represents a major cause of pneumonia in critically ill patients. Although bacteremia may complicate S aureus pneumonia, the epidemiology of and outcomes associated with bacteremia in this syndrome are poorly described. MATERIALS AND METHODS: We retrospectively identified (January 2005-December 2007) all patients admitted to the hospital with S aureus pneumonia necessitating mechanical ventilation. All subjects underwent lower airway and concurrent blood cultures. The prevalence of bacteremia served as a primary end point. We assessed the impact of bacteremia on mortality and length of stay via either logistic regression or a Cox proportional hazard model, respectively. In both models, we controlled for multiple covariates (eg, demographics, severity of illness, comorbidities, and appropriateness of initial antibiotics). We subsequently developed a prediction rule to identify subjects likely to have concurrent bacteremia based on variables assessed at the time of presentation. RESULTS: The cohort included 59 patients (mean +/- SD age, 58.0 +/- 17.4 years; 55.9% male, 59.3% methicillin resistant, 39.0% crude mortality). Bacteremia complicated nearly 20% of cases. The mortality rate in those with bacteremia was 39.1% vs 8.3% in persons without bacteremia (P = .007). Three variables were independently associated with mortality in S aureus pneumonia: age, need for vasopressors, and concurrent bacteremia. Bacteremia independently conferred a 6 fold increase in the risk for death (adjusted odds ratio, 5.96; 95% confidence interval [CI], 1.08-33.10). Bacteremia also correlated with a longer length of stay. The adjusted hazard ratio for remaining hospitalized if bacteremic was 2.65 (95% CI, 1.14-6.18). For the clinical prediction rule for concurrent bacteremia, we assigned points as follows: 2 points if the patient had received prior antibiotic therapy and 1 point each for acute lung injury and for the need for vasopressors. As the total score increased, the prevalence of bacteremia increased (P < .001). As a screening test for bacteremia in S aureus pneumonia, the scoring system had good predictive value. The area under the receiver operating curve measured 0.83 (95% CI, 0.72-0.94). CONCLUSIONS: Bacteremia often arises in S aureus pneumonia and is associated with both increased morbidity and mortality. Several simple clinical factors to determine clinical features identify patients with S aureus pneumonia likely to have simultaneous bacteremia. PMID- 21036522 TI - Morbidity and mortality characteristics of morbidly obese patients admitted to hospital and intensive care units. AB - BACKGROUND: The purpose of this study is to evaluate the outcomes of hospitalized morbidly obese inpatients. METHODS: In this retrospective cohort study, we reviewed the records of all adult morbidly obese patients (defined as body mass index [BM]) >40 kg/m(2) upon admission) admitted to tertiary university hospital from 2000 to 2008. Primary outcome was hospital mortality. Secondary outcomes were hospital and intensive care unit (ICU) length of stay (LOS), need for and duration of mechanical ventilation (MV), and tracheostomy rates. We divided patients into quartiles based on their admission BMI. Baseline characteristics and outcomes were reported for each quartile. RESULTS: Over the 8-year period, we reviewed 897 admissions for 545 patients. The median number of admissions was 1 per patient (mean, 2.44 +/- 2.9), with a range of 1 to 20. A total of 40.9% had more than one admission. Morbidly obese patients were more likely to be admitted to a medical service. Higher BMI quartiles had higher rates of ICU admission, MV, and rate of tracheostomy. Although the higher BMI quartiles had longer hospital LOS, hospital mortality did not significantly differ. CONCLUSIONS: As BMI increases, utilization of medical resources also increases such as ICU admission, MV, longer hospital LOS, and tracheostomy. Although overall BMI interquartile mortality rates do not differ significantly in our study, utilization of valuable and costly hospital resources is a major challenge facing health care delivery. Our findings indicate the need for increased efforts and novel strategies for treatment, prevention, and resource allocation to deal with this emerging challenge. PMID- 21036523 TI - Respiratory impact of paracentesis in cirrhotic patients with acute lung injury. AB - INTRODUCTION: Ascites may contribute to the loss of lung volume and alter the gas exchange in cirrhotic patients with acute lung injury (ALI). AIM: The aim of the study was to evaluate the effects of paracentesis on respiratory parameters in ventilated cirrhotic patients with ALI. STUDY DESIGN: This was a prospective trial in an intensive care unit of a university hospital. PATIENTS AND METHODS: Thirty-one cirrhotic patients on mechanical ventilation (with ALI) requiring paracentesis were included in this study. Arterial blood gases, intraabdominal pressures, ventilator parameters, and lung volumes were measured before and after the ascitic drainage. RESULTS: Following paracentesis, the intraabdominal pressure decreased (24.1 +/- 7.0 vs 12.3 +/- 8.9 mm Hg, P < .0001) and the Pao(2)/Fio(2) improved significantly (190.0 +/- 65.2 vs 284.9 +/- 76.1 mm Hg, P < .0001), without hemodynamic disturbances. End-expiratory lung volume, markedly reduced before drainage, increased significantly following paracentesis (Delta end-expiratory lung volume: +463 +/- 249 mL, P = .0009). No adverse effects related to the paracentesis were encountered. CONCLUSION: In contrast to ventilatory recruitment maneuvers, paracentesis is a simple and well-tolerated technique able to improve oxygenation and alveolar recruitment without the risk of the lung overdistension in severely hypoxemic cirrhotic patients. PMID- 21036524 TI - Delivered dose of continuous venovenous hemofiltration predicts outcome in septic patients with acute kidney injury: a retrospective study. AB - PURPOSE: In continuous venovenous hemofiltration (CVVH) issues like timing and dose remain controversial, particularly in sepsis. The objective of this study is to examine which CVVH characteristic best predicts mortality in sepsis-induced acute kidney injury (AKI). MATERIALS AND METHODS: We retrospectively studied all consecutive patients with sepsis-induced AKI requiring CVVH in a 1.5-year period. Patient, sepsis, and CVVH characteristics, including timing, dose, mode, type of substitution fluid and of anticoagulation, and azotemic control were evaluated. Primary outcome was survival at day 28 after the start of CVVH. RESULTS: Of the 97 patients, 43 (44%) died up to day 28 after the start of CVVH. In univariate analyses, the delivered dose of CVVH was about 10% higher in survivors than nonsurvivors (median, 23 vs 20 mL kg(-1) h(-1), P = .01). In multivariate analyses, a lower delivered CVVH dose contributed to predict higher mortality, independently of disease severity, type of substitution fluid, and azotemic control. In a Kaplan-Meier curve, a delivered dose less than 19.7 mL kg(-1) h(-1) was associated with shorter survival (P = .006). CONCLUSION: Our retrospective data suggest that in sepsis-induced AKI requiring CVVH, delivered dose, rather than timing, mode of administration, and azotemic control, is an independent predictor of mortality. A lower delivered dose is associated with higher mortality. PMID- 21036525 TI - Increased myeloperoxidase enzyme activity in plasma is an indicator of inflammation and onset of sepsis. AB - INTRODUCTION: Circulating lipopolysaccharides released from bacteria may activate both neutrophils and monocytes. The activated neutrophils release myeloperoxidase (MPO), a specific enzyme with strong oxidative activity. The aim of this study was to evaluate MPO enzyme activity in plasma of critically ill patients and to check the hypothesis that these concentrations in plasma would be higher in sepsis and systemic inflammatory conditions, as neutrophils release their contents before proliferating in response to stress. MATERIAL AND METHODS: Blood samples were collected from 105 critically ill patients admitted to the intensive care unit, consisting of those with systemic inflammatory response syndrome (n = 42), sepsis (n = 37), and septic shock (n = 26). Plasma MPO enzyme activity was determined by o-dianisidine-H(2)O(2) method, modified for 96-well plates. RESULTS: The plasma MPO enzyme activity in sepsis patients was significantly higher than that in the control group (mean, 2.4 +/- 1.8 in sepsis and 1.86 +/- 1.2 nmol per milligram protein per 10 minutes in systemic inflammatory response syndrome vs 0.32 +/- 0.11 nmol per milligram protein per 10 minutes in healthy controls). Mean plasma lactate levels in sepsis (7.8 +/- 1.2 mmol/L) and shock patients (9.5 +/- 1.2 mmol/L) and cytokines like tumor necrosis factor-alpha, interleukin-8, and interleukin-1beta were simultaneously evaluated to establish onset of inflammation and sepsis. These results show that neutrophil activation occurring during inflammation and sepsis could be detected by plasma MPO concentration. CONCLUSION: The plasma MPO concentrations may be a marker of the neutrophil proliferation and severity of inflammation. PMID- 21036526 TI - Comparison of 3 different multianalyte point-of-care devices during clinical routine on a medical intensive care unit. AB - PURPOSE: Multianalyte point-of-care (POC) devices are important to guide clinical decisions in critical care. However, the use of different devices in one hospital might cause problems. Therefore, we evaluated 3 commonly used POC devices and analyzed accuracy, reliability, and bias. METHODS: Seventy-four arterial blood samples were analyzed by 3 POC devices (Cobas, Roche Diagnostics, Mannheim, Germany; ABL800 Flex, Radiometer GmbH, Germany; Gem Premiere, Instrumentation Laboratory, Germany). For selected parameters, samples were also analyzed in the central laboratory. pCO2, pO2, SO2, bicarbonate and standard bicarbonate, sodium, potassium, calcium, pH, lactate, base excess (BE[B] and BEecf), glucose, hemoglobin, and hematocrit were compared. RESULTS: For most parameters, only minor, although statistically significant, changes were observed between the POC devices. For pO2, BE(B), hemoglobin, and hematocrit, clinically significant differences were found. CONCLUSION: Although POC devices are of high standard and overall comparability between devices is high, there might be a clinically relevant bias between devices, as found in our study for pO2, BE(B), hemoglobin, and hematocrit. This can be of importance when interpreting results of the same patient obtained from different POC devices, as it could happen when a patient is transferred within a hospital where different devices are used. PMID- 21036527 TI - Early impact of medical emergency team implementation in a country with limited medical resources: a before-and-after study. AB - PURPOSE: The purpose of the study was to determine whether earlier clinical intervention by a medical emergency team (MET) can improve patient outcomes in an Asian country. METHODS: A nonrandomized study was performed during two 6-month periods before and after the introduction of a MET. RESULTS: The rates of cardiac arrests and "potentially preventable" cardiac arrests were lower after MET introduction, but the differences did not reach statistical significance. There was a statistically significant decrease in the incidence of cardiac arrests in the first 3 months of the academic year (2.3 vs 1.2 per 1000 admissions, P = .012). Introduction of MET reduced the time interval from physiologic derangement meeting MET activation criteria to intensive care unit (ICU) admission ("derangement-to-ICU interval") (10.8 vs 6.3 hours, P < .001). Multivariate analysis revealed that the mortality of unplanned ICU admissions was independently associated with simplified acute physiology score 3 and "derangement-to-ICU interval." CONCLUSIONS: Introduction of a MET reduced the number of cardiac arrests in the general ward during the first 3 months of the academic year. Introduction of MET also decreased the "derangement-to-ICU interval," which was an independent predictor of survival in patients with unplanned ICU admissions. Therefore, MET introduction may lead to improved outcomes for hospitalized patients in a country with limited medical resources. PMID- 21036528 TI - The effects of vasoactive drugs on pulse pressure and stroke volume variation in postoperative ventilated patients. AB - INTRODUCTION: Although pulse pressure variation (PPV) and stroke volume variation (SVV) during mechanical ventilation have been shown to predict preload responsiveness, the effect of vasoactive therapy on PPV and SVV is unknown. METHODS: Pulse pressure variation and SVV were measured continuously in 15 cardiac surgery patients for the first 4 postoperative hours. Pulse pressure variation was directly measured from the arterial pressure waveform, and both PPV and SVV were also calculated by LiDCO Plus (LiDCO Ltd, Cambridge, United Kingdom) before and after volume challenges or changes in vasoactive drug infusions done to sustain cardiovascular stability. RESULTS: Seventy-one paired events were studied (38 vasodilator, 10 vasoconstrictor, 14 inotropes, and 9 volume challenges). The difference between the measured and LiDCO-calculated PPV was 1% +/- 7% (1.96 SD, 95% confidence interval, r(2) = 0.8). Volume challenge decreased both PPV and SVV (15% to 10%, P < .05 and 13% to 9%, P = .09, respectively). Vasodilator therapy increased PPV and SVV (13% to 17% and 9% to 15%, respectively, P < .001), whereas increasing inotropes or vasoconstrictors did not alter PPV or SVV. The PPV/SVV ratio was unaffected by treatments. CONCLUSION: Volume loading decreased PPV and SVV; and vasodilators increased both, consistent with their known cardiovascular effects. Thus, SVV and PPV can be used to drive fluid resuscitation algorithms in the setting of changing vasoactive drug therapy. PMID- 21036529 TI - Evolutive physicochemical characterization of diabetic ketoacidosis in adult patients admitted to the intensive care unit. AB - PURPOSE: The aim of this study was to characterize the first 48-hour evolution of metabolic acidosis of adult patients with diabetic ketoacidosis admitted to the intensive care unit. MATERIALS AND METHODS: We studied 9 patients retrieved from our prospective collected database, using the physicochemical approach to acid base disturbances. RESULTS: Mean (SD) age was 34 (13) years; mean (SD) Acute Physiology and Chronic Health Evaluation II score was 16 (10); mean (SD) blood glucose level on admission was 480 (144) mg/dL; mean (SD) pH was 7.17 (0.18); and mean (SD) standard base excess was -16.8 (7.7) mEq/L. On admission, a great part of metabolic acidosis was attributed to unmeasured anions (strong ion gap [SIG], 20 +/- 10 mEq/L), with a wide range of strong ion difference (41 +/- 10 mEq/L). During the first 48 hours of treatment, 297 +/- 180 IU of insulin and 9240 +/- 6505 mL of fluids were used. Metabolic improvement was marked by the normalization of pH, partial correction of standard base excess, and a reduction of hyperglycemia. There was a significant improvement of SIG (7.6 +/- 6.2 mEq/L) and a worsening of strong ion difference acidosis (36 +/- 5 mEq/L) in the first 24 hours, with a trend toward recuperation between 24 and 48 hours (38 +/- 6 mEq/L). CONCLUSION: Initial metabolic acidosis was due to SIG, and the treatment was associated with a significant decrease of SIG with an elevation of serum chloride above the normal range. PMID- 21036530 TI - Determination of capillary hemoglobin levels using the HemoCue system in intensive care patients. AB - PURPOSE: The study aimed to compare hemoglobin (Hb) values determined using the portable HemoCue system (HemoCue Hb 201+; HemoCue AB, Angelholm, Sweden) with laboratory Hb level determination. MATERIALS AND METHODS: Adult patients hospitalized in our surgical intensive care unit who required an Hb level determination were included. To determine Hb level, one drop of arterial (A) or venous (V) blood was analyzed using HemoCue (HemoCue([A/V])), and also with an automated analyzer in the laboratory (Hb reference method, or Hb Lab([A/V])). Capillary blood (Cap) sample obtained simultaneously by fingerstick was analyzed using HemoCue (HemoCue([Cap])). Factors that could interfere with the accuracy of fingerstick measurements were also studied. Paired Hb level measurements were compared by Bland and Altman analysis (Hb Lab([A/V]) vs HemoCue([A/V]) and HemoCue([Cap])). RESULTS: One hundred fifty blood samples were obtained from 79 patients. The mean absolute differences between Hb Lab [A] and HemoCue [A], Hb Lab [V] and HemoCue [V] and Hb Lab [A/V] and HemoCue [Cap] were 0.1 g/dl (95% confidence interval, -1.9 to + 2.2 g/dl), 0.1 g/dl (95%CI, -2.5 to +2.6 g/dl) and 1.1 g/dl (95%CI, -3.6 to + 5.8 g/dl, respectively. Edema was the sole independent risk factor for discordance between HemoCue([Cap]) and Hb Lab([A/V]) (odds ratio, 6.65; 95% CI, 1.99-22.21; P < .001]. CONCLUSIONS: Hemoglobin level determination using HemoCue should not be used in critically patients, especially when capillary blood samples are used and/or in presence of edema. PMID- 21036531 TI - Reduced mortality after the implementation of a protocol for the early detection of severe sepsis. AB - OBJECTIVE: We evaluate the impact that implementing an in-hospital protocol for the early detection of sepsis risk has on mortality from severe sepsis/septic shock. METHODS: This was a prospective cohort study conducted in 2 phases at 2 general hospitals in Brazil. In phase I, patients with severe sepsis/septic shock were identified and treated in accordance with the Surviving Sepsis Campaign guidelines. Over the subsequent 12 months (phase II), patients with severe sepsis/septic shock were identified by means of active surveillance for signs of sepsis risk (SSR). We compared the 2 cohorts in terms of demographic variables, the time required for the identification of at least 2 SSRs, compliance with sepsis bundles (6- and 24-hour), and mortality rates. RESULTS: We identified 217 patients with severe sepsis/septic shock (102 during phase I and 115 during phase II). There were significant differences between phases I and II in terms of the time required for the identification of at least 2 SSRs (34 +/- 48 vs 11 +/- 17 hours; P < .001) and in terms of in-hospital mortality (61.7% vs 38.2%; P < .001). CONCLUSION: The early detection of sepsis promoted early treatment, reducing in-hospital mortality from severe sepsis/septic shock. PMID- 21036532 TI - Intensive care unit admissions for community-acquired pneumonia are seasonal but are not associated with weather or reports of influenza-like illness in the community. AB - PURPOSE: The aims of this study were to determine if there is seasonal variation in the number of intensive care unit (ICU) admissions for community-acquired pneumonia (CAP) and if there is a relationship between these admissions and weather or reports of influenza-like illness in the community. MATERIALS AND METHODS: In this time series analysis in 3 medical-surgical ICUs (8, 13, and 20 beds) in the Vancouver region, we included patients admitted to adult ICUs for CAP between January 2002 and March 2006. We used Poisson regression to analyze the association between weekly number of ICU admissions for CAP, and average temperature, range in temperature, total precipitation, and cases of influenza like illness/100 physician visits reported by sentinel physicians in the community. RESULTS: In 740 patients admitted to ICUs for CAP, admissions peaked each year in the winter-spring months. In multivariate models, a sine function with a single annual peak was independently associated with number of patients admitted to ICU for CAP (rate ratio [95% confidence interval], 1.12 [1.00, 1.26]), but neither the weather measurements nor the weekly rate of reported influenza-like illness was significantly associated. CONCLUSION: Intensive care unit admissions for CAP are seasonal, but neither weather measurements nor weekly rate of reported influenza-like illness in the community is associated with these admissions. PMID- 21036533 TI - Dynamic response of liquid-filled catheter systems for measurement of blood pressure: precision of measurements and reliability of the Pressure Recording Analytical Method with different disposable systems. AB - PURPOSE: We aimed to compare the effects of a blood pressure transducer system specifically manufactured to limit underdamping artifacts with those of a standard system on hemodynamic parameter estimation and accuracy. MATERIALS AND METHODS: Forty-three consecutive patients undergoing vascular surgery at the University of Florence, Italy, were included. Arterial blood pressure signal was simultaneously registered with 2 MostCare monitors, connected to the artery either by a standard transducer or a specific transducer manufactured to avoid underdamping artifacts (Resonance Over-Shoot Eliminator [R.O.S.E.]; Becton Dickinson, Becton Drive, NJ). Patients were divided into 2 groups: absence (C group) or presence (R group) of underdamping/resonance artifacts of blood pressure signal. Systolic blood pressure, cardiac index, maximal pressure/time ratio (dP/dt(MAX)), and cardiac cycle efficiency were recorded every 30 seconds for 30 minutes. A total of 2675 measurements were performed with 34.9% incidence of underdamping/resonance artifacts. RESULTS: All hemodynamic parameters showed clinically acceptable differences in the C group; in contrast, the results differed greatly in the R group between standard and R.O.S.E. transducer (systolic blood pressure bias, 16.7 mm Hg; cardiac index bias, 0.24 L min(-1) m( 2); dP/dt(MAX) bias, 0.92 mm Hg/ms; cardiac cycle efficiency bias, 0.018 units). CONCLUSIONS: Underdamping/resonance artifacts frequently affect blood pressure measurement in operating rooms and intensive care units and cause severe overestimation of systolic blood pressure and incorrect estimation of hemodynamic parameters when the pulse contour method is used. PMID- 21036534 TI - Risk factors for prolonged intensive care unit stay and hospital mortality in acute drug-poisoned patients: an evaluation of the physiologic and laboratory parameters on admission. AB - BACKGROUND: The share of patients receiving intensive care treatment because of acute drug poisoning is 2% to 14% of all patients receiving intensive care. The outcome is mainly good and the length of intensive care is usually less than 2 days. Our aim was to recognize the risks for prolonged intensive care and hospital mortality using admission Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scoring in acute drug-poisoned patients. METHODS: A national, prospectively collected intensive care unit (ICU) data registry was used for analysis. Data from 28 ICUs in university and secondary nonteaching hospitals from 1998 to 2004 were available. RESULTS: There were 255 admissions because of acute drug poisoning, which represented 4.5% of all admissions. The mean length of the ICU stay was 32.1 hours. Of the patients, 11.5% had a prolonged ICU stay (>48 hours). Hospital mortality was 2.3%. The mean Acute Physiology and Chronic Health Evaluation II score was 14.4 (SD, 8.1) and the mean Sequential Organ Failure Assessment score was 4.8 (SD, 3.0). The mean Glasgow Coma Scale score on admission was 9.7 (SD, 4.7). In the multivariate analysis, the highest odds ratios for prolonged ICU stay were respiratory failure, lowered platelet count, and renal dysfunction. In the multivariate analysis, the highest odds ratios for hospital mortality were respiratory failure, renal failure, and hypotension. CONCLUSIONS: In acute intoxication, respiratory and renal dysfunction and failure are risk factors for poor outcome. PMID- 21036535 TI - Oxygen saturation/fraction of inspired oxygen ratio is a simple predictor of noninvasive positive pressure ventilation failure in critically ill patients. AB - PURPOSE: Noninvasive positive pressure ventilation (NPPV) can improve outcomes of critically ill patients. Early and simple predictors of NPPV outcome could improve clinical management of patients with respiratory failure. MATERIALS AND METHODS: A prospective observational study was conducted in a medical intensive care unit of a tertiary medical center. Patients requiring NPPV were included and followed. Clinical data including respiratory mechanics at the time of NPPV initiation, and clinical outcomes were recorded. Data were analyzed to identify variables that distinguished NPPV success or failure. RESULTS: A total of 133 patients were included in the study. Noninvasive positive pressure ventilation success rate was 41%. Patients diagnosed with malignancy had only 29% NPPV success rate. Among patients without malignancy, higher oxygen saturation, oxygen saturation/fraction of inspired oxygen (SF) ratios, and SF/minute ventilation ratios were associated with NPPV success. Receiver operating characteristic curve analyses identify SF ratio less than 98.5 to be a specific (89% specificity, P = .013) predictor of NPPV failure. Furthermore, for patients requiring at least 24 hours of NPPV support, tidal volume/predicted body weight ratio negatively correlated with respiratory improvement. CONCLUSIONS: For patients without malignancy, SF ratios at the time of NPPV initiation discriminated NPPV success and failure, and could be used to help guide the management of critically ill patients who require ventilatory support. PMID- 21036536 TI - Determinants of activity and participation in preschoolers with developmental delay. AB - According to the International Classification of Functioning, Disability and Health model endorsed by the World Health Organization, activity (the execution of a task or action by an individual), and participation (involvement in a life situation) are important components in the assessment of health and functioning of an individual. The purpose of this study was to compare the activity performance and school participation of preschool children with developmental delay (DD) and age-matched typically developing children, and to identify the determinants of activity and participation in preschoolers with DD. Fifty-four children with DD (37 boys, 17 girls; mean age: 66 months) and 54 age-matched typically developing children (34 boys, 20 girls; mean age: 65 months) were recruited from the mainstream preschools with integrated program units. Activity and participation were evaluated using the Vineland Adaptive Behavior Scales (VABS) and School Function Assessment (SFA). Other factors that may influence activity and participation such as impairments in sensory, motor, and mental functioning, and other contextual factors (e.g. family income) were also measured. The DD group had significantly lower VABS (p < 0.001) and SFA (p<0.001) scores than controls, indicating suboptimal activity and participation. Multiple regression analysis revealed that deficits in social and motor skills, and in inattention/hyperactivity, were significantly associated with activity and participation in children with DD, accounting for approximately 35-37% of the variance in the VABS and SFA scores ( p<0.001). In conclusion, deficits in social and motor functioning, and attention-deficit hyperactivity disorder-related symptoms, are important determinants of activity and participation in preschoolers with DD. One may consider targeting these specific areas to enhance activity and participation amongst these children. PMID- 21036537 TI - A neurodynamical model for working memory. AB - Neurodynamical models of working memory (WM) should provide mechanisms for storing, maintaining, retrieving, and deleting information. Many models address only a subset of these aspects. Here we present a rather simple WM model in which all of these performance modes are trained into a recurrent neural network (RNN) of the echo state network (ESN) type. The model is demonstrated on a bracket level parsing task with a stream of rich and noisy graphical script input. In terms of nonlinear dynamics, memory states correspond, intuitively, to attractors in an input-driven system. As a supplementary contribution, the article proposes a rigorous formal framework to describe such attractors, generalizing from the standard definition of attractors in autonomous (input-free) dynamical systems. PMID- 21036538 TI - Detection of granularity in dermoscopy images of malignant melanoma using color and texture features. AB - Granularity, also called peppering and multiple blue-grey dots, is defined as an accumulation of tiny, blue-grey granules in dermoscopy images. Granularity is most closely associated with a diagnosis of malignant melanoma. This study analyzes areas of granularity with color and texture measures to discriminate granularity in melanoma from similar areas in non-melanoma skin lesions. The granular areas in dermoscopy images of 74 melanomas and 14 melanomas in situ were identified and manually selected. For 200 non-melanoma dermoscopy images, those areas which most closely resembled granularity in color and texture were similarly selected. Ten texture and twenty-two color measures were studied. The texture measures consisted of the average and range of energy, inertia, correlation, inverse difference, and entropy. The color measures consisted of absolute and relative RGB averages, absolute and relative RGB chromaticity averages, absolute and relative G/B averages, CIE X, Y, Z, X/Y, X/Z and Y/Z averages, R variance, and luminance. These measures were calculated for each granular area of the melanomas and the comparable areas in the non-melanoma images. Receiver operating characteristic (ROC) curve analysis showed that the best separation of melanoma images from non-melanoma images by granular area features was obtained with a combination of color and texture measures. Comparison of ROC results showed greater separation of melanoma from benign lesions using relative color than using absolute color. Statistical analysis showed that the four most significant measures of granularity in melanoma are two color measures and two texture measures averaged over the spots: relative blue, relative green, texture correlation, and texture energy range. The best feature set, utilizing texture and relative color measures, achieved an accuracy of 96.4% based on area under the receiver operating characteristic curve. PMID- 21036539 TI - Applying a statistical PTB detection procedure to complement the gold standard. AB - This paper investigates a novel statistical discrimination procedure to detect PTB when the gold standard requirement is taken into consideration. Archived data were used to establish two groups of patients which are the control and test group. The control group was used to develop the statistical discrimination procedure using four vectors of wavelet coefficients as feature vectors for the detection of pulmonary tuberculosis (PTB), lung cancer (LC), and normal lung (NL). This discrimination procedure was investigated using the test group where the number of sputum positive and sputum negative cases that were correctly classified as PTB cases were noted. The proposed statistical discrimination method is able to detect PTB patients and LC with high true positive fraction. The method is also able to detect PTB patients that are sputum negative and therefore may be used as a complement to the gold standard. PMID- 21036540 TI - Le Fort I distraction osteogenesis of the edentulous maxilla. AB - Rehabilitation of the edentulous patient with atrophic ridges is a problem especially when compounded with a severe prognathic inter-arch relationship. It is difficult to rehabilitate these patients prosthetically without correction of the malrelation of the jaws. The established surgical techniques for correcting combined sagittal and vertical discrepancies of edentulous jaws are often prolonged and complex with attendant morbidity. This article presents a novel, simple method of correction of severe interarch sagittal discrepancy (more than 15 mm) by performing distraction osteogenesis at Le Fort I level using an internal maxillary distraction device. This method is a simple, predictable and stable option for the correction of a severe, unfavourable intermaxillary relation in edentulous patients. PMID- 21036541 TI - An MEG study of alpha modulation in patients with schizophrenia and in subjects at high risk of developing psychosis. AB - BACKGROUND: Selective attention involves a dynamic interaction between attentional control systems and brain oscillations. In auditory processing, selective attention toward task-relevant stimuli and the inhibition of irrelevant information can be considered as aspects of top-down attentional control. Oscillatory rhythms in the alpha band have been found to play an important role during top-down processing. Because attention deficits have been noted in patients with schizophrenia, we examined alpha oscillations in schizophrenia and in the prodromal phase of psychosis. METHODS: The present study compared alpha oscillations using measures of both spectral power and inter-trial coherence in 17 subjects at ultra-high-risk, 10 patients with schizophrenia, and 18 matched normal control subjects. Whole-head magnetoencephalography (MEG) was conducted during an auditory oddball task to investigate alpha brain activity related to selective attention to target stimuli and selective inhibition of irrelevant stimuli. RESULTS: Patients with schizophrenia showed diminished alpha event related desynchronization compared with the control subjects, while the ultra high-risk subjects had values intermediate between the control subjects and schizophrenia patients. Similarly, alpha inter-trial phase coherence was lower in the schizophrenia patients than the ultra-high-risk subjects, and lower in the ultra-high-risk subjects than the normal control subjects. Furthermore, alpha band activity in the parieto-occipital region was more severely depressed in the schizophrenia patients than the ultra-high-risk subjects. CONCLUSIONS: The altered alpha band activity in the ultra-high-risk group indicates that a deficit in top-down attentional control exists before the onset of psychosis. The alpha event-related desynchronization and inter-trial coherence may reflect a functional decline in the prodromal phase of schizophrenia. PMID- 21036542 TI - Pre-illness cannabis use and the early course of nonaffective psychotic disorders: associations with premorbid functioning, the prodrome, and mode of onset of psychosis. AB - INTRODUCTION: Limited research indicates that pre-illness cannabis use may result in an earlier age at onset of psychosis, though little is known about the influence of prior cannabis use on the premorbid and prodromal phases. This study examined the effects of prior or concurrent cannabis (as well as nicotine and alcohol) use on: (1) early adolescent (12-15 years) premorbid functioning, (2) late adolescent (16-18 years) premorbid functioning, (3) two features of the prodrome, and (4) mode of onset of psychosis. METHODS: Participants included 109 well-characterized first-episode patients hospitalized in public-sector settings. Assessments included ages at initiation of first, weekly, and daily use of substances, the Premorbid Adjustment Scale, the Symptom Onset in Schizophrenia inventory, and a consensus-based best estimate of mode of onset. RESULTS: Participants having used cannabis at <=15 years had better early adolescence social functioning than those who had not used cannabis (p=0.02). Conversely, those who had used cannabis at <=18 years had poorer late adolescence academic functioning (p<0.001). Participants having used cannabis before onset of psychotic symptoms did not differ from those who had not in terms of having had an identifiable prodrome or the number of prodromal symptoms experienced. Whereas 42% of those having used cannabis daily had an acute mode of onset of psychosis, only 20% of those without prior daily cannabis use had an acute onset (p=0.04). CONCLUSIONS: Findings suggest that cannabis use is associated with premorbid social and academic functioning and mode of onset. Further research is warranted to elucidate the complex associations between cannabis use and diverse early course features. PMID- 21036544 TI - What percentage of people in the general population satisfies the current clinical at-risk criteria of psychosis? PMID- 21036543 TI - Paternal age related schizophrenia and cardiac autonomic regulation profiles. PMID- 21036545 TI - The advantages of hair follicle pluripotent stem cells over embryonic stem cells and induced pluripotent stem cells for regenerative medicine. AB - Multipotent adult stem cells have many potential therapeutic applications. Our recent findings suggest that hair follicles are a promising source of easily accessible multipotent stem cells. Stem cells in the hair follicle area express the neural stem cell marker nestin, suggesting that hair-follicle stem cells and neural stem cells have common features. Nestin-expressing hair follicle stem cells can form neurons and other cell types, and thus adult hair follicle stem cells could have important therapeutic applications, particularly for neurologic diseases. Transplanted hair follicle stem cells promote the functional recovery of injured peripheral nerve and spinal cord. Recent findings suggest that direct transplantation of hair-follicle stem cells without culture can promote nerve repair, which makes them potentially clinically practical. Human hair follicle stem cells as well as mouse hair follicle stem cells promote nerve repair and can be applied to test the hypothesis that human hair follicle stem cells can provide a readily available source of neurologically therapeutic stem cells. The use of hair follicle stem cells for nerve regeneration overcomes critical problems of embryonic stem cells or induced pluripotent stem cells in that the hair follicle stem cells are multipotent, readily accessible, non-oncogenic, and are not associated with ethical issues. PMID- 21036546 TI - Elevated risk of second primary cancer in patients with cutaneous malignant melanoma: a nationwide cohort study in Taiwan. AB - BACKGROUND: It has been described that Caucasian patients with cutaneous malignant melanoma (CMM) are at an increased risk of developing second primary cancer. However, no large-scale study of second primary cancer in CMM patients has been conducted among Asians, who have distinctly different skin types. OBJECTIVE: We sought to access the risk of second primary cancer among CMM patients based on data from a nationwide database in Taiwan. METHODS: Utilizing the catastrophic illness database of Taiwan's National Health Insurance Research Database, we identified 2665 CMM patients without prior cancers in the period from 1997 to 2008. The standard incidence ratio (SIR) of each cancer was calculated. RESULTS: The mean age +/- standard deviation at diagnosis of CMM was 62.2 +/- 17.4 years. The mean annual incidence was 0.9 cases per 100,000 people. The overall cancer risk was elevated (SIR: 2.54), with younger patients having a higher risk. The risk remained elevated during the first five years after the CMM diagnosis. CMM patients had a higher risk of developing cancers of eye (SIR: 275.68), connective tissue (SIR: 43.45), brain (SIR: 21.03), and non-melanoma skin cancer (SIR: 17.71). CONCLUSION: CMM patients have a 2.54-fold risk of second primary cancer, with younger patients at increased risk. The risk remains elevated during the first five years after the diagnosis of CMM. The sites with highest risk of second primary cancer are eye, connective tissue, brain, and non melanoma skin cancer. PMID- 21036547 TI - Surveillance of antimicrobial susceptibility of aerobic and facultative Gram negative bacilli isolated from patients with intra-abdominal infections in China: the 2002-2009 Study for Monitoring Antimicrobial Resistance Trends (SMART). AB - The objective of this study was to investigate the distribution and susceptibility of aerobic and facultative Gram-negative bacilli (GNB) isolated from patients with intra-abdominal infections (IAIs) in China. From 2002 to 2009, minimum inhibitory concentrations of 14 antibiotics for 3420 aerobic and facultative GNB from up to eight hospitals in six cities were determined by the broth microdilution method. Enterobacteriaceae comprised 82.9% (2834/3420) of the total isolates, with Escherichia coli (49.2%) being the most commonly isolated species followed by Klebsiella pneumoniae (17.0%), Enterobacter cloacae (5.8%) and Citrobacter freundii (2.3%). Amongst the antimicrobial agents tested, the three carbapenems (ertapenem, imipenem and meropenem) were the most active agents against Enterobacteriaceae, with susceptibility rates of 96.1-99.6% (2002-2009), 98.2-100% (2002-2009) and 99.6-100% (2002-2004), respectively, followed by amikacin (86.8-95.1%) and piperacillin/tazobactam (84.5-94.3%). Susceptibility rates of all tested third- and fourth-generation cephalosporins against Enterobacteriaceae declined by nearly 30%, with susceptibility rates of 40.2%, 39.1%, 56.3% and 51.8% in 2009 for ceftriaxone, cefotaxime, ceftazidime and cefepime, respectively. The occurrence of extended-spectrum beta-lactamases increased rapidly, especially for E. coli (from 20.8% in 2002 to 64.9% in 2009). Susceptibility of E. coli to ciprofloxacin decreased from 57.6% in 2002 to 24.2% in 2009. The least active agent against Enterobacteriaceae was ampicillin/sulbactam (SAM) (25.3-44.3%). In conclusion, Enterobacteriaceae were the major pathogens causing IAIs, and carbapenems retained the highest susceptibility rates over the 8-year study period. Third- and fourth-generation cephalosporins, fluoroquinolones and SAM may not be ideal choices for empirical therapy of IAIs in China. PMID- 21036548 TI - Increasing escitalopram dose is associated with fewer discontinuations than switch or combination approaches in patients initially on escitalopram 10 mg. AB - PURPOSE: To examine the relationship between different intervention approaches and subsequent real-life outcomes in patients changing treatment from escitalopram 10 mg. METHOD: This was a retrospective cohort study of patients starting antidepressant treatment between 2002 and 2004. Data were extracted from a US health-insurance reimbursement claims database. Eligible patients started escitalopram 10 mg and changed within 3 months to: escitalopram >=20 g; another antidepressant; or a combination of escitalopram with another antidepressant. Medication persistence and healthcare costs over 3 months were compared between the treatment groups. RESULTS: Overall, 37,791 patients started escitalopram 10 mg. Of the 12,830 patients (34%) who changed treatment, 56% increased escitalopram dose, 26% switched antidepressant and 18% combined escitalopram with another antidepressant. Patients in the switch and combination groups had significantly higher rates of non-persistence (56% and 91%, respectively) vs the dose-increase group (39%; both P<0.001). Combination-group patients incurred significantly greater costs vs the dose-increase group ($2805 vs $1767, respectively; P<0.001). CONCLUSION: Results suggest that increasing escitalopram dose in patients responding inadequately to 10 mg is associated with higher persistence rates vs the other treatment approaches. Receiving an increased dose of escitalopram was associated with significantly lower costs than combining escitalopram 10 mg with another antidepressant. PMID- 21036550 TI - Evaluation of side effects using the BARS, SAS and AIMS in pediatric psychopharmacologic studies. PMID- 21036551 TI - Modelling psychiatric measures using Skew-Normal distributions. AB - Data from psychiatric research frequently exhibit departures from Normality. Methods which utilise the data optimally to model the distribution directly are available. We highlight the issue of modelling skewness, resulting from screening instruments where the majority of respondents are healthy individuals and few participants have a value reflecting particular disorders. PMID- 21036552 TI - A four-year naturalistic prospective study of cardiometabolic disease in antipsychotic-treated patients. AB - The relationship between antipsychotic use and cardiovascular morbidity and mortality is controversial. There is a lack of long-term prospective studies investigating changes in cardiometabolic risk in patients treated with antipsychotic drugs. We report data from a 4-year prospective study. Patients (89) underwent detailed metabolic and cardiovascular risk assessment at 4-years which included anthropometric assessment, blood pressure, lipid profile, and an oral glucose tolerance test. We used the homeostatic model assessment to determine insulin resistance, and calculated 10-year cardiovascular risk scores. Mean age of subjects was 44.7 (+/- 11.5) years, and 52% were male. The prevalence of type 2 diabetes was 8%, and 38.4% fulfilled diagnostic criteria for the metabolic syndrome. With the exception of increased central adiposity over the 4 year follow-up period (p < 0.001), other cardiometabolic parameters were generally unchanged. There was a high prevalence of dyslipidaemia, but only 16.9% were prescribed lipid-lowering treatment. Commencing lipid-lowering therapy was associated with a reduction in cardiovascular risk score (OR 7.9, 95% CI = 1.3 to 48.7; p = 0.02). Patients established on longer-term antipsychotic treatment show less dramatic metabolic changes than those occurring in the early stages of treatment, but have a high burden of cardiovascular risk. Lipid-lowering therapy is associated with a significant reduction in cardiovascular risk. PMID- 21036549 TI - Cardiovascular and metabolic risk in outpatients with schizoaffective disorder treated with antipsychotics: results from the CLAMORS study. AB - AIM: To assess the coronary heart disease (CHD) risk and prevalence of the metabolic syndrome (MS) in patients with schizoaffective disorder (SD) receiving antipsychotics. METHODS: Patients meeting DSM-IV criteria for SD and receiving antipsychotic treatment were recruited in a retrospective, cross-sectional, multicenter study (the CLAMORS study). MS was defined as at least three of the following components: waist circumference greater than 102 cm (men)/greater than 88 cm (women); serum triglycerides greater or equal to 150 mg/dl; HDL cholesterol less than 40 mg/dl (men)/less than 50 mg/dl (women); blood pressure greater or equal to 130/85 mmHg; fasting blood glucose greater or equal to 110 mg/dl. The 10 year CHD risk was assessed by the Systematic coronary risk evaluation (SCORE) (cardiovascular mortality) and Framingham (any cardiovascular event) functions. Clinical severity was assessed using the PANSS and CGI-S scales. RESULTS: A total of 268 valuable patients with SD (127 men, 48.1%), 41.9+/-12.3 years (mean+/ S.D.), were analyzed. The 10-year overall cardiovascular mortality and CV-event risk were 0.8+/-1.6 (SCORE) and 6.5+/-6.8 (Framingham), respectively. A high/very high risk of any CV event (Framingham>=10%) was associated with severity [CGI-S=3 4; OR: 4.32 (1.15-16.26), P=0.03)]. MS was present in 26.5% (95%CI: 21.2-31.8) of subjects, without gender differences, but significantly associated with patient's impression of severity: CGI=3-4; OR=1.90 (0.83-4.36), and CGI=5-7; OR=3.13 (1.06 9.24), P=0<0.001, and age [OR=1.91 (1.09-3.34), P<0.024)]. CONCLUSIONS: CHD risk and MS prevalence were high among patients with SD, being MS prevalence associated with age and severity of disease. PMID- 21036553 TI - Assessment of social anxiety in first episode psychosis using the Liebowitz Social Anxiety scale as a self-report measure. AB - OBJECTIVE: Social anxiety is a common problem in psychotic disorders. The Liebowitz Social Anxiety Scale, Self-Rating version (LSAS-SR) is a widely used instrument to capture different aspects of social anxiety, but its psychometric properties have not been tested in this patient group. The aims of the present study were to evaluate the psychometric properties of the LSAS-SR in patients with first episode psychosis, to investigate whether it differentiated between active and passive social withdrawal and to test which clinical factors contributed to current level of social anxiety. METHOD: A total of 144 first episode psychosis patients from the ongoing Thematically Organized Psychosis (TOP) study were included at the time of first treatment. Diagnoses were set according to the Structured Clinical Interview (SCID-1) for DSM-IV. A factor analysis was carried out and the relationship of social anxiety to psychotic and general symptomatology measured by the Positive and Negative Syndrome Scale (PANSS) was evaluated. Possible contributors to social anxiety were analyzed using multiple hierarchic regression analysis. RESULTS: The factor analysis identified three subscales: public performance, social interaction and observation. All three subscales showed satisfactory psychometric properties, acceptable convergent and discriminate properties, and confirmed previous findings in social anxiety samples. Self-esteem explained a significant amount of the variance in social anxiety, even after adjusting for the effects of delusions, suspiciousness and depression. CONCLUSION: The study shows that the LSAS-SR can be used in this patient group, that social anxiety is strongly related to both behavioral social avoidance and to self-esteem. The results support the use of this measure in assessment of social anxiety in both clinical settings and in research. PMID- 21036554 TI - The impact of the social network, stigma and empowerment on the quality of life in patients with schizophrenia. AB - OBJECTIVE: The quality of life (QOL) of patients with schizophrenia has been found to be positively correlated with the social network and empowerment, and negatively correlated with stigma and depression. However, little is known about the way these variables impact on the QOL. The study aims to test the hypothesis that the social network, stigma and empowerment directly and indirectly by contributing to depression influence the QOL in patients with schizophrenia and schizoaffective disorders. METHOD: Data were collected on demographic and clinical variables, internalized stigma, perceived devaluation and discrimination, empowerment, control convictions, depression and QOL. Structural equation modelling (SEM) was applied to examine the impact of the above-mentioned constructs on QOL. RESULTS: The influences of the social network, stigma, empowerment and depression on QOL were supported by the SEM. A poor social network contributed to a lack of empowerment and stigma, which resulted in depression and, in turn, in poor QOL. Interestingly, however, the social network and stigma did not show a direct effect on QOL. CONCLUSION: Following a recovery approach in mental health services by focusing on the improvement of the social network, stigma reduction and especially on the development of personal strength has the potential to reduce depression in patients with psychosis and improving their QOL. PMID- 21036555 TI - The stability of severe thought disorders and mature thinking. AB - The aim of this study was to investigate whether severe formal thought disorders and mature thinking are stable among adoptees (=187) drawn from the Finnish adoptive family study of schizophrenia. A group of 93 adoptees genetically at high risk (HR) and 94 at low risk (LR) for schizophrenia were assessed blindly and reliably using the Index of Primitive Thought (IPT) and the Index of Integration (IOI). Two assessments of the IPT and the IOI were performed with the mean interval of 11 years. Comparisons of the IPT and the IOI mean scores were conducted both at baseline and at follow-up between adoptees at low and high genetic risk, gender, and psychiatric status. The main result was that the IOI as well as the IPT of the adoptees at the initial assessment predicted the IOI and the IPT estimated at follow-up, thus indicating the stability of severe formal thought disorders and mature thinking over time. The stability of IOI or IPT was not related to genetic risk, gender or psychiatric status or their interactions. PMID- 21036557 TI - A general protocol for temperature calibration of MAS NMR probes at arbitrary spinning speeds. AB - A protocol using (207)Pb NMR of solid lead nitrate was developed to determine the temperature of magic-angle spinning (MAS) NMR probes over a range of nominal set temperatures and spinning speeds. Using BioMAS and FastMAS probes with typical sample spinning rates of 8 and 35 kHz, respectively, empirical equations were devised to predict the respective sample temperatures. These procedures provide a straightforward recipe for temperature calibration of any MAS probe. PMID- 21036556 TI - Pregnenolone sulfate and its enantiomer: differential modulation of memory in a spatial discrimination task using forebrain NMDA receptor deficient mice. AB - This study examined the role of forebrain N-methyl-D-aspartate receptors (NMDA Rs) in the promnesiant effects of natural (+) pregnenolone sulfate (PREGS) and its synthetic (-) enantiomer ent-PREGS in young adult mice. Using the two-trial arm discrimination task in a Y-maze, PREGS and ent-PREGS administration to control mice increased memory performances. In mice with a knock-out of the NR1 subunit of NMDA-Rs in the forebrain, the promnesiant effect of ent-PREGS was maintained whereas the activity of PREGS was lost. Memory enhancement by PREGS involves the NMDA-R activity in the hippocampal CA1 area and possibly in some locations of the cortical layers, whereas ent-PREGS acts independently of NMDA-R function. PMID- 21036558 TI - Flower-like agglomerates of hydroxyapatite crystals formed on an egg-shell membrane. AB - Flower-like hydroxyapatite agglomerates formed on the upper side and lower side of an egg-shell membrane were intensively investigated using a uniquely designed crystallizer. First the ion driving force was calculated in theory. In addition the influences of various factors, such as temperature, pH value, and holding time, on the morphology and crystallinity of the agglomerates were studied in detail by means of FESEM, TEM and XRD. It was found that flower-like hydroxyapatite agglomerates with high crystallinity can be produced under higher temperature, larger pH value, and moderated holding time. The information generated is relevant to the formation process of bone. PMID- 21036559 TI - Gradient immobilization of a cell adhesion RGD peptide on thermal responsive surface for regulating cell adhesion and detachment. AB - Using surface initiated atomic transfer radical polymerization (ATRP) and an injection method, a poly(N-isopropylacrylamide)-b-poly(acrylic acid)-g-RGD (PNIPAAm-b-PAA-g-RGD) gradient surface was prepared. First, a thermoresponsive surface with a constant thickness of PNIPAAm was fabricated, onto which the AA monomers were block copolymerized using the PNIPAAm macromolecules as initiators. During this process, a continuous injection method was employed to yield a molecular weight gradient of PAA on the underlying uniform PNIPAAm layer. RGD peptide was finally covalently immobilized onto the PAA gradient by carbodiimide chemistry. In vitro culture of HepG2 cells showed that immobilization of the RGD peptide could accelerate cell attachment, while the thermoresponsive layer beneath could effectively release the cells by simply lowering temperature. Thus, the PNIPAAm-b-PAA-g-RGD gradient surface, combining the thermal response with cell affinity properties, can well regulate the cell adhesion and detachment, which may thus be useful for investigation of cell-substrate interactions with a smaller number of samples. PMID- 21036560 TI - The effect of the prior flow velocity on the structural organization of aggregated erythrocytes in the quiescent blood. AB - Usually, investigations of erythrocyte aggregation at rest are focused on effects of the strength of erythrocyte-erythrocyte attractive interactions and the volume fraction of the cells, whereas the role of prior flow velocity has not been thoroughly investigated. The aim of this study is to fill this gap. The main conclusions extracted from time records of the complex admittance of blood are as follows: (1) Dispersion of blood in a prior flow into discrete aggregates increases the mesh size of network, which, as has been recently shown, is formed in the quiescent blood. (2) If the energy of the flow field is sufficient to prevent the formation of face-to-side intercellular links, so that the dispersed phase consists of linear rouleaux, changes in the mesh size correlate positively with the length of rouleaux. (3) At slower prior flow velocities, the cells are combined into branched aggregates. As the degree of branching increases, the effect becomes less important. (4) The effects of the length of linear rouleaux and the degree of branching of ramified aggregates on the mesh size are qualitatively similar for suspensions with different aggregating media. (5) Erythrocytes suspended in strongly aggregating media form at low flow conditions a network-like structure. In this case, unlike high and moderate prior flow regimes, the mesh size of RBC network at rest is less than that formed after the stoppage of completely dispersed blood. PMID- 21036561 TI - [Alopecia, congenital ichthyosis, and growth delay, what is the diagnosis?]. PMID- 21036562 TI - [Unusual presentation of scurvy mimicking a neuroblastoma]. AB - Scurvy, a disease related to ascorbic acid deficiency, remains rare in industrial countries. Ascorbic acid is a vitamin that intervenes most notably in the synthesis of collagen and catecholamines. We report the case of a 2-year-old boy hospitalized in a pediatric oncology unit because of an unusual presentation of scurvy revealed by pain and a significant increase in urinary catecholamine levels, raising fear of a neuroblastoma. PMID- 21036564 TI - [Hypoplasia of the internal carotid artery: a rare cause of cerebral ischemic stroke in children]. AB - Hypoplasia of the carotid arteries is a rare congenital anomaly which, when symptomatic, presents as cerebral ischemia or hemorrhage. We report a case of hypoplasia of the carotid arteries revealed by cerebral ischemic stroke in an infant with hereditary spherocytosis. The diagnosis was confirmed by MR angiography. We describe this rare cause of stroke in children and the characteristics of its association with hereditary spherocytosis. PMID- 21036563 TI - [The alliance of the parent, child and the nurse to challenge medical error]. AB - A group composed of parents, nurses, and physicians involved in pediatric cancerology has reflected on medical errors within the Espace Ethique de l'Assistance publique-Hopitaux de Paris. Based on narratives and qualitative analysis of histories and testimonies, this discussion aimed at exploring the causes, circumstances, and impacts of medical errors on the relations between these individuals. The study demonstrated that some circumstances actually promote medical errors, such as hard working conditions, mistrust, unreliable control procedures, not listening to parents, and caring for children in extreme situations of pain and suffering. Errors almost always result from the accumulation of several shortcomings. The tensions raised by a medical error can be overcome, provided that parents and caregivers trust each other from the onset of disease and that the medical errors are disclosed in a sincere way, whatever the medical consequences. The feelings raised by the painful experience of a medical error do not solely depend on the severity of the consequences, since seemingly benign errors may lead to long-term trauma, whereas severe errors, even those leading to death, do not necessarily breach trust. The keyword here is permanent vigilance. The capacity of caregivers to question their practice, from both a technical and ethical point of view, will determine their ability to learn from an error for the future. The depth and quality of this questioning, in the best of times encouraged by the institution, may also help children affected by a medical error and their family to move forward in their personal history, beyond such painful experiences. PMID- 21036565 TI - [Bordetella bronchiseptica-associated acute chest syndrome in a child with sickle cell disease]. AB - We describe a case of acute chest syndrome associated with Bordetella bronchiseptica pneumonia in a child with sickle cell disease. B. bronchiseptica is recognized as an important pathogen of the respiratory tract for a large variety of animal species. This zoonotic agent has been frequently associated with chronic and recurrent infections. In humans, the bacterium acts as an opportunistic pathogen affecting mostly immunocompromised patients or those with preexisting respiratory diseases. This case and literature review provides an opportunity to discuss the risk factors, treatment, follow-up, and prevention of such zoonotic infections in the context of a lack of cross-protection of new pertussis vaccines. PMID- 21036566 TI - How to use contextual knowledge in medical case-based reasoning systems: a survey on very recent trends. AB - OBJECTIVES: This paper aims at systematizing the ways in which the contextual knowledge embedded in the case library can support decision making, within case based reasoning (CBR) systems. In particular, CBR applications to the medical domain are considered. METHODS AND MATERIAL: After a quick survey on the definition and on the role of context in artificial intelligence research, we have focused on CBR, with a particular emphasis on medical applications. In this field, we have identified a number of very recent contributions, which strongly recognize context per se as a major knowledge source. These contributions propose to maintain and to rely on contextual information, in order to support human reasoning in different fashions. RESULTS: We have distinguished three main directions in which contextual knowledge can be resorted to, in order to optimize physicians' decision making. Such directions can be summarized as follows: (1) to reduce the search space in the case retrieval step; (2) to maintain the overall knowledge content always valid and up to date, and (3) to adapt knowledge application and reasoning to local/personal constraints. We have also properly categorized the surveyed works within these three clusters, and identified the most significant ones, able to exploit contextual knowledge along more than one direction. CONCLUSIONS: Innovative applications of the contextual knowledge recorded in the case library, described and systematized in this paper, can trace promising research directions for the future. PMID- 21036567 TI - beta-D-Glucosyl-(1-4)-alpha-L-thevetosides of 17beta-digitoxigenin from seeds of Cerbera manghas L. induces apoptosis in human hepatocellular carcinoma HepG2 cells. AB - beta-D-Glucosyl-(1-4)-alpha-L-thevetosides of 17beta-digitoxigenin (GHSC-73) is a cardiac glycoside isolated from the seeds of Cerbera manghas L. GHSC-73 reduced viability of HepG2 cells in a time- and dose-dependent manner without decreasing the viability of Chang human liver cells and Swiss albino 3T3 fibroblasts, induced efficiently stimulated apoptosis in HepG2 cells as evidenced by DNA fragmentation, annexin V/PI binding assay and DAPI staining. This apoptotic process was accompanied by the activation of the effector caspase-3, the loss of mitochondrial membrane potential (DeltaPsi(m)) and translocation of AIF from the mitochondrion to the nucleus in HepG2 cells. In addition, a broad-spectrum caspase inhibitor (z-VAD-fmk) tested in this experiment partially prevent HepG2 cells from GHSC-73-induced cell death, but did not affect translocation of AIF from the mitochondrion to the nucleus after GHSC-73 treatment. Our results firstly show that GHSC-73 inhibits the growth of HepG2 cells through caspase dependent and -independent apoptosis pathways. PMID- 21036568 TI - Possible ameliorative effects of kolaviron against reproductive toxicity in sub lethally whole body gamma-irradiated rats. AB - Ionizing radiation is one of the environmental factors that may contribute to reproductive dysfunction by a mechanism involving oxidative stress. We investigated the possible ameliorative effects of kolaviron (KV) (a biflavonoid from the seeds of Garcinia kola) on sperm characteristics, testicular lipid peroxidation (LPO) and antioxidant status after a whole body gamma-irradiation in Wistar rats. Vitamin C (VC) served as standard antioxidant in this study. The study consists of four groups of 6 rats each. Group I received corn oil, whereas group II received a single dose of gamma-radiation (5 Gy). The animals in groups III and IV were pretreated with KV (250 mg/kg) and VC (250 mg/kg) by oral gavage five times in a week, respectively, for 6 weeks prior to and 8 weeks after exposure to gamma-radiation. Gamma-irradiation resulted in a significant (p<0.05) decrease in body weight and relative testes weight. Also, gamma-irradiation significantly (p<0.05) decreased the activities of superoxide dismutase, catalase and glutathione S-transferase as well as glutathione level, but markedly elevated malondialdehyde levels in the serum and testes. Irradiated rats showed testicular degeneration with concomitant decrease in sperm motility and viability. Although sperm abnormalities significantly increased, it has no effect on the epididymal sperm count. KV and VC significantly (p<0.05) decreased the body weight loss and increased relative testes weights of the rats. Furthermore, supplementation of KV and VC ameliorated radiation-induced toxicity by increasing the activities of antioxidant enzymes, decreased LPO and abrogated testicular degeneration. Taken together, gamma-irradiation caused reproductive dysfunction by depleting the antioxidant defence system in the rats, while administration of KV or VC ameliorated the radiation-induced testicular toxicity. PMID- 21036570 TI - Development and implementation of a technical and didactical training program for student tutors in the dissection course. AB - BACKGROUND: student tutors have a long tradition in gross anatomy instruction. However, the full potential of the tutors is generally not tapped, since little attention is paid to their technical and didactical training. The aim of this paper is to report a systematic approach to the development, didactic reasoning and implementation of a curriculum for training student tutors in gross anatomy. METHODS: the training program was developed using the six-step approach of Kern's curriculum development model. For needs assessment, the literature research was amended by a survey among the 1st and 2nd year students of the dissection course (n=167) and two independent 90 min focus group interviews with the tutors who supervised these students (n=15). Protocols were transcribed and analyzed by margin coding. The training curriculum was setup on the basis of these data. RESULTS: corresponding to the literature, the students want student tutors with good teaching competence as well as adequate content knowledge and technical competence. Supporting that, the tutors request a training program enhancing their didactic skills as well as their knowledge of content and working using relevant methods. Thus, a combined didactic and professional training program has been developed. Six professional and 11 didactic learning objectives were defined. A 3 weeks training curriculum was implemented, using microteaching and group exercises for didactics and active dissection for technical training. Both parts were interlocked on a contextual and practical level. CONCLUSION: our focus group analyses revealed that a specific training program for student tutors in the dissection course is necessary. We describe a feasible task-oriented training curriculum combining didactic and professional objectives. PMID- 21036569 TI - Does a combined technical and didactical training program improve the acceptance of student tutors in the dissection course? A prospective controlled randomized study. AB - BACKGROUND: student tutors in the dissection course are expected to meet high demands on their job. We developed a combined technical and didactical training on the basis of literature review and needs assessment. The three-week training program comprised dissection as well as presentation techniques, group dynamics and activating teaching methods. A randomized, controlled, single-blind study was set up to test whether there is a difference between the tutee's perception of the tutor competences, comparing trained and untrained tutors. METHODS: a total of 10 trained and 10 untrained tutors (control group) were enlisted in the study. The acceptance of the training program was measured with a questionnaire (11 items, 5-point Likert scale) where the tutees rated the competences of the tutors. The tutees were assigned randomly to their tutor and blinded to his/her training. RESULTS: the tutees assessed the trained tutors better in all categories compared to the untrained tutors. A significantly better score (p<0.05) was stated for the categories "conveying basic dissection techniques" (4.31 +/- 0.86 vs. 3.89 +/- 1.05), "positive group atmosphere" (4.69 +/- 0.73 vs. 4.44 +/- 0.88), "learning support" (4.24 +/- 1.03 vs. 3.79 +/- 1.16) and "visualisation" (3.99 +/- 1.11 vs. 3.56 +/- 1.17). In self-assessment, the trained tutors rated themselves significantly better after the training compared to before in all categories. CONCLUSION: The specific training curriculum for tutors in the dissection course, focusing on the improvement of content knowledge, technical and didactical competencies, is well accepted by the tutees and tutors. PMID- 21036571 TI - Investigation of the influence of EPs(r) 7630, a herbal drug preparation from Pelargonium sidoides, on replication of a broad panel of respiratory viruses. AB - The Pelargonium sidoides extract EPs(r) 7630 is an approved drug for the treatment of acute bronchitis in Germany. The postulated mechanisms underlying beneficial effects of EPs(r) 7630 in bronchitis patients include immunomodulatory and cytoprotective effects, inhibition of interaction between bacteria and host cells, and increase of cilliary beat frequency on respiratory cells. Here, we investigated the influence of EPs(r) 7630 on replication of a panel of respiratory viruses. Determination of virus-induced cytopathogenic effects and virus titres revealed that EPs(r) 7630 at concentrations up to 100 MUg/ml interfered with replication of seasonal influenza A virus strains (H1N1, H3N2), respiratory syncytial virus, human coronavirus, parainfluenza virus, and coxsackie virus but did not affect replication of highly pathogenic avian influenza A virus (H5N1), adenovirus, or rhinovirus. Therefore, antiviral effects may contribute to the beneficial effects exerted by EPs(r) 7630 in acute bronchitis patients. PMID- 21036572 TI - Anti-thrombosis effect of diosgenin extract from Dioscorea zingiberensis C.H. Wright in vitro and in vivo. AB - Thrombus formation in blood vessel plays an important role in the pathogenesis and progression of atherosclerosis and cardiovascular diseases. Extract of Dioscorea zingiberensis C.H. Wright (D. zingiberensis) is demonstrated to posses activities for curing cardiovascular diseases such as coronary heart disease and angina pectoris. However, there were few studies on anti-thrombosis activity of it. We investigated the anti-thrombosis effect of diosgenin from D. zingiberensis (Dio) in vitro and in vivo on inferior vena cava ligation thrombosis rat model and pulmonary thrombosis mice model. We evaluated the protective effect of Dio by measuring the platelet aggregation, activated partial thromboplastin time (APTT), thrombin time (TT), prothrombin time (PT) and the venous thrombosis in rats and the bleeding time, clotting time and protection rate in mice. Results showed that Dio inhibited platelet aggregation, thrombosis and prolonged APTT, PT and TT in rats in a dose-dependent manner. They also prolonged the bleeding time, clotting time and increased protection rate in mice in a dose-dependent manner. Taken together, these findings suggested that Dio which contained 95% diosgenin had anti-thrombosis activity. Dio executives the anti-thrombosis activity through improving the anticoagulation function, inhibiting platelet aggregation and thrombosis. PMID- 21036573 TI - Reversing beta-lactam antibiotic resistance of Staphylococcus aureus with galangin from Alpinia officinarum Hance and synergism with ceftazidime. AB - The purpose of this investigation was to extract and identify the bioactive phytochemicals from smaller galanga (Alpinia officinarum Hance). The antibacterial, synergy effects and primary mechanism of action of galangin and ceftazidime against S. aureus DMST 20651 are also investigated by minimum inhibitory concentration (MIC), checkerboard, killing curve determinations, enzyme assay and electronmicroscopy method. The rhizomes chloroform extract of this plant showed that these compounds were galangin, kaempferide and kaempferide 3-O-beta-D-glucoside, which had not been previously reported in this species. Synergistic FIC indices were observed in the combination of test flavonoids (galangin, quercetin and baicalein) and all selected beta-lactams (methicillin, ampicillin, amoxicillin, cloxacillin, penicillin G and ceftazidime) (FIC index, <0.02-0.11). The combination of ceftazidime at 5 MUg/ml and 5 MUg/ml of test flavonoids (galangin, quercetin and baicalein) exhibited synergistic effect by reduced the cfu/ml of this strain to 1*10(3) over 6 and throughout 24 h. Galangin showed marked inhibitory activity against penicillinase and beta-lactamase. Electronmicroscopy clearly showed that the combination of galangin and ceftazidime caused damage to the ultrastructures of the cells of this strain. It was concluded that galangin, quercetin and baicalein exhibited the potential to reverse bacterial resistance to beta-lactam antibiotics against penicillin resistant S. aureus (PRSA). This may involve three mechanisms of action that galangin inhibit protein synthesis and effect on PBP 2a, interact with penicillinase and cause cytoplasmic membrane damage. These findings lead us to develop a new generation of phytopharmaceuticals that may use galangin, quercetin and baicalein in combination with ceftazidime to treat PRSA that currently almost untreatable microorganism. The anti-PRSA activity and mode of action of galangin is reported for the first time. These in vitro results have to be still confirmed in an animal test or in humans. PMID- 21036574 TI - Ellagitannins from Phyllanthus muellerianus (Kuntze) Exell.: Geraniin and furosin stimulate cellular activity, differentiation and collagen synthesis of human skin keratinocytes and dermal fibroblasts. AB - Leaves from Phyllanthus muellerianus (Kuntze) Exell. are traditionally used for wound healing in Western Africa. Aqueous extracts of dried leaves recently have been shown to stimulate proliferation of human keratinocytes and dermal fibroblasts. Within bioassay-guided fractionation the ellagitannins geraniin (1), corilagin (2), furosin (3), the flavonoids quercetin-3-O-beta-D-glucoside (isoquercitrin), kaempferol-3-O-beta-D-glucoside (astragalin), quercetin-3-O-D rutinoside (rutin), gallic acid, methyl gallate, caffeic acid, chlorogenic acid, 3,5-dicaffeoylquinic acid and caffeoylmalic acid (phaselic acid) have been identified in P. muellerianus for the first time. Geraniin was shown to be the dominant component of an aqueous extract. Suitable analytical methods for quality control of geraniin in P. muellerianus extract (methanol/water, 70/30) have been developed and validated based on ICH guidelines (ICH-compliant protocol). Geraniin and furosin increased the cellular energy status of human skin cells (dermal fibroblasts NHDF, HaCaT keratinocytes), triggering the cells towards higher proliferation rates, with fibroblasts being more sensitive than keratinocytes. Highest stimulation of NHDF by geraniin was found at 5 MUM, and of keratinocytes at 50-100 MUM. Furosin stimulated NHDF at about 50 MUM, keratinocytes at about 150-200 MUM. Necrotic cytotoxicity of geraniin, as measured by LDH release, was observed at 20 MUM for NHDF and 150 MUM for keratinocytes. Toxicity of furosin--less than that of geraniin--was observed at > 400 MUM. Furosin and geraniin stimulated the biosynthesis of collagen from NHDF at 50 MUM and 5-10 MUM respectively. Geraniin at 105 MUM significantly stimulated the differentiation in NHEK while furosin had a minor influence on the expression of involucrin and cytokeratins K1 and K10. The study proves clearly that hydrophilic extracts from P. muellerianus and especially the lead compound geraniin exhibit stimulating activity on dermal fibroblasts and keratinocytes, leading to increased cell proliferation, barrier formation and formation of extracellular matrix proteins. From these findings the traditional clinical use of such extracts for wound healing seems to be justified. PMID- 21036575 TI - Preparative chromatography of flavonoids and saponins in Gynostemma pentaphyllum and their antiproliferation effect on hepatoma cell. AB - A preparative column chromatographic method was developed to isolate flavonoids and saponins from Gynostemma pentaphyllum, a Chinese Medicinal herb, and evaluate their antiproliferation effect on hepatoma cell Hep3B, with the standards rutin and ginsenoside Rb(3) being used for comparison. Initially the powdered G. pentaphyllum was extracted with ethanol, followed by eluting flavonoids and saponins with ethanol-water (30:70, v/v) and 100% ethanol, respectively, in an open-column containing 5 g of Cosmosil 75C(18)-OPN, and then subjected to HPLC-MS analysis. The flavonoid fraction was mainly composed of quercetin- and kaempferol glycosides, while in saponin fraction, both ginsenoside Rb(3) and ginsenoside Rd dominated. Both fractions were more effective against Hep3B cells than the standards rutin and ginsenoside Rb(3), with the cell cycle being arrested at G0/G1 phase for all the treatments. Additionally, the inhibition effect followed a dose-dependent increase for all the sample treatments. The result of this study may be used as a basis for possible phytopreparations in the future with G. pentaphyllum as raw material. PMID- 21036576 TI - Fraxinus excelsior seed extract FraxiPureTM limits weight gains and hyperglycemia in high-fat diet-induced obese mice. AB - PURPOSE: The aim of this study was to determine whether a Fraxinus excelsior L. seed extract, FraxiPureTM (0.5% in the diet), limits weight gain and hyperglycemia in mice. In a previous report, we identified several secoiridoids in FraxiPureTM, some of which activated peroxisome proliferator-activated receptor alpha (PPARalpha) in vitro and inhibited the differentiation of 3T3-L1 preadipocyte cells. In a separate study, FraxiPureTM reduced glycemia in healthy volunteers, following an oral glucose tolerance test. These findings suggest that FraxiPureTM has antiobesity and antihyperglycemia effects. MATERIALS AND METHODS: FraxiPureTM was tested in mice that were fed a high-fat diet over 16 weeks and compared with low-fat and high-fat diet controls. Weight gain, omental and retroperitoneal fat, fasting blood glucose, and fasting blood insulin were measured. RESULTS: FraxiPureTM reduced gains in body weight by 32.30% (p < 0.05), omental fat by 17.92%, and retroperitoneal fat by 17.78%. FraxiPureTM also lowered fasting blood glucose levels by 76.52% (p < 0.001) and plasma insulin levels by 53.43% (p < 0.05) after 16 weeks. Moreover, FraxiPureTM lowered liver weight gains by 63.62% (p < 0.05) and the incidence of fatty livers by 66.67%. CONCLUSIONS: Our novel results demonstrate the antiobesity effects of chronic administration of an F. excelsior seed extract and confirm its ability to regulate glycemia and insulinemia. In addition, this extract, which is rich in secoiridoid glucosides, protects against obesity-related liver steatosis. PMID- 21036577 TI - Isolation of substances with antiproliferative and apoptosis-inducing activities against leukemia cells from the leaves of Zanthoxylum ailanthoides Sieb. & Zucc. AB - Extraction of the leaves of Zanthoxylum ailanthoides Sieb. & Zucc. affords extracts and four isolated compounds which exhibit activities against leukemia cells. The chloroform-soluble fraction (ZAC) of the crude extract of this plant showed cytotoxic activity against human promyelocytic leukemia (HL-60) and myelomonocytic leukemia (WEHI-3) cells with IC(50) values of 73.06 and 42.22 MUg/mL, respectively. The active ZAC was further separated to yield pheophorbide a methyl ester (1), pheophorbide-b methyl ester (2), 13(2)-hydroxyl (13(2)-S) pheophorbide-a methyl ester (3) and 13(2)-hydroxyl (13(2)-R) pheophorbide-b methyl ester (4) whose structures were confirmed by spectroscopic methods. Compounds 2-4 showed cytotoxic activities against both leukemia cells with IC(50) value in the range of 46.76-79.43 nM, whereas compound 1 exhibited only weak cytotoxic activity. The extracts and compounds 1-4 also induced apoptosis and DNA damage in leukemia cells after treatment. The results suggested that the Z. ailanthoides is biologically active against leukemia cells. PMID- 21036578 TI - The effectiveness and efficacy of Rhodiola rosea L.: a systematic review of randomized clinical trials. AB - OBJECTIVE: To critically assess the current evidence from randomized clinical trials (RCTs) for or against the effectiveness or efficacy of Rhodiola rosea. DATA SOURCES: Systematic literature searches were performed in six electronic databases: AMED (1985-July 2009), CINAHL (1982-July 2009), The Cochrane Library (search in July 2009), EMBASE (1974-July 2009), MEDLINE (1950-July 2009) and Web of Science (searched in July 2009). No language restrictions were imposed. Reference lists of all retrieved articles were searched, and experts and manufacturers were contacted for unpublished RCT. REVIEW METHODS: RCTs testing the efficacy or effectiveness of mono-preparations of R. rosea as sole treatment administered orally against a control intervention in any human individual suffering from any condition or healthy human volunteers were included. Studies were selected, data extracted, and quality assessed by two independent reviewers. RESULTS: Eleven RCTs met the inclusion criteria; all were placebo-controlled. Six trials investigated the effects of R. rosea on physical performance, four on mental performance, and two in patients diagnosed with mental health condition. The methodological quality of most trials was moderate or good. Only few mild adverse events were reported. CONCLUSION: R. rosea may have beneficial effects on physical performance, mental performance, and certain mental health conditions. There is, however, a lack of independent replications of the single different studies. Five of the 10 RCTs reached more than three points on the Jadad score (i.e., good quality). More research seems warranted. PMID- 21036579 TI - Central nervous system activities of two diterpenes isolated from Aloysia virgata. AB - Using the guide of a competitive assay for the benzodiazepine binding site in the gamma-aminobutyric acid type A receptor (GABA(A)), two active diterpenes were isolated from the aerial parts of Aloysia virgata (Ruiz & Pavon) A.L. Jussieu var. platyphylla (Briquet) Moldenke. These compounds, identified as (16R) 16,17,18-trihydroxyphyllocladan-3-one (1) and (16R)-16,17-dihydroxyphyllocladan-3 one (2) on the basis of spectral data, competitively inhibited the binding of [(3)H]-FNZ to the benzodiazepine binding site with K(i)+/-S.E.M. values of 56+/ 19 MUM and 111+/-13 MUM, respectively. The behavioral actions of these diterpenes, intraperitoneally (i.p.) administered in mice, were examined in the plus-maze, holeboard, locomotor activity and light/dark tests. Compound 1 exhibited anxiolytic-like effects in mice evidenced by a significant increase of the parameters measured in the holeboard test (the number of head dips at 0.3 mg/kg and 3 mg/kg, the rears at 1 mg/kg and the time spent head-dipping at 3 mg/kg), in the plus-maze assay (the percentage of open arm entries at 1 mg/kg) and in the light/dark test (the time in light and the number of transitions at 1 mg/kg). Compound 2 augmented the number of rearings in the holeboard apparatus (at 0.3 mg/kg and 1 mg/kg) and the locomotor activity (at 1 mg/kg). These results reveal the presence of neuroactive compounds in Aloysia virgata. PMID- 21036580 TI - The effect of crocin and safranal, constituents of saffron, against subacute effect of diazinon on hematological and genotoxicity indices in rats. AB - In this study, the effect of crocin and safranal was studied against subacute toxicity of diazinon (DZN) on hematological and genotoxicity indices in rats. The rats were divided into 16 groups consisted of 6 rats in control, diazinon, vitamin E, vitamin E and DZN, crocin (3 doses), crocin (3 doses) and DZN, safranal (3 doses), safranal (3 doses) and DZN groups. Vitamin E (200 IU/kg), safranal at doses 0.025, 0.05 and 0.1 ml/kg and crocin at doses 50, 100 and 200 mg/kg were injected intraperitoneally to rats three times per week alone or with DZN (20 mg/kg/day, orally) for 4 weeks. Hematological parameters were evaluated at the end of 4 weeks. The evaluation of genotoxicity was done using the micronucleus assay. Vitamin E and, at lower doses, safranal (0.025 and 0.05 ml/kg) and crocin (50 mg/kg) restored the reduction of red blood cell, hemoglobin and hematocrit indices induced by DZN. These agents at some doses also prevented the reduction in platelets counts indices in diazinon treated group. A significant increase in reticulocyte was induced by diazinon. Vitamin E, safranal (0.025 or 0.05 ml/kg) and all doses of crocin decreased this effect of diazinon. In all doses vitamin E, crocin and safranal did not inhibit the effect of diazinon on RBC cholinesterase activity. A significant increase in micronucleus indices was seen with diazinon. Vitamin E, safranal and crocin could not prevent this genotoxicity. This study showed that vitamin E, safranal and crocin (without effects on cholinesterase) reduced diazinon hematological toxicity, but they did not prevent the genotoxicity induced by diazinon. PMID- 21036581 TI - Pharmacokinetics, tissue distribution and excretion study of dl-praeruptorin A of Peucedanum praeruptorum in rats by liquid chromatography tandem mass spectrometry. AB - dl-Praeruptorin A (Pd-Ia), isolated from Chinese traditional herbal medicine Peucedanum praeruptorum Dunn, has been proved to be a novel Ca2+-influx blocker and K+-channel opener, and displayed bright prospects in prevention and therapy of cardiac diseases. The aim of this study was to investigate the pharmacokinetics, tissue distribution and excretion of Pd-Ia in rats following a single intravenous (i.v.) administration. The levels of Pd-Ia in plasma, tissues, bile, urine and feces were measured by a rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The results showed that Pd-Ia was rapidly distributed and then eliminated from rat plasma and manifested linear dynamics in dose range of 5-20 mg/kg. The mean elimination half life (t(1/2) of Pd-Ia for 5, 10 and 20 mg/kg dose were 57.46, 60.87 and 59.01 min, respectively. The major distribution tissues of Pd-Ia in rats were spleen, heart and lung, and low polarity enabled Pd-Ia to cross the blood-brain barrier. There was no long-term accumulation of Pd-Ia in rat tissues. Total recoveries of Pd-Ia within 24 h were low (0.097% in bile, 0.120% in urine and 0.009% in feces), which might be resulted from liver first pass effect. PMID- 21036582 TI - Hypolipidemic and antioxidant activities of sanchi (radix notoginseng) in rats fed with a high fat diet. AB - Sanchi, also known as radix notoginseng, is a Chinese traditional medicine prepared from roots of the herb Panax notoginseng. Sanchi is traditionally used as a hemostatic to control internal and external bleeding but also shows diverse bioactivities that include increasing coronary blood flow and reducing myocardial oxygen consumption and blood pressure. Although research into the potential cardioprotective effects of sanchi is ongoing in the field of traditional Chinese medicine, we sought to explore potential benefits in cardiovascular disorders associated with excess cholesterol and hyperlipidemia. We have investigated the effects of sanchi as a dietary supplement on hyperlipidemia and oxidative stress in male Sprague-Dawley rats maintained on a high-fat diet. Diets were supplemented with sanchi at 0.25%, 0.5% and 1% (w/w) for four weeks, while control animals received no supplement. Sanchi administration to hyperlipidemic rats resulted in a significant decline in serum levels of total cholesterol, triglycerides and low density lipoprotein-cholesterol, with an increase in serum high-density lipoprotein-cholesterol levels. Treated animals also showed reduced levels of hepatic HMG-CoA reductase. Furthermore, sanchi improved hepatic antioxidant status as assessed by superoxide dismutase and glutathione peroxidase activities and reduced levels of lipid peroxidation. These results suggest that sanchi consumption can improve lipid profiles, inhibit peroxidation, and increase the activity of antioxidant enzymes, and is thereby likely to reduce the risk of coronary heart disease associated with hyperlipidemia and oxidative stress. PMID- 21036583 TI - Olive (Olea europaea) leaf extract effective in patients with stage-1 hypertension: comparison with Captopril. AB - A double-blind, randomized, parallel and active-controlled clinical study was conducted to evaluate the anti-hypertensive effect as well as the tolerability of Olive leaf extract in comparison with Captopril in patients with stage-1 hypertension. Additionally, this study also investigated the hypolipidemic effects of Olive leaf extract in such patients. It consisted of a run-in period of 4 weeks continued subsequently by an 8-week treatment period. Olive (Olea europaea L.) leaf extract (EFLA((r))943) was given orally at the dose of 500 mg twice daily in a flat-dose manner throughout the 8 weeks. Captopril was given at the dosage regimen of 12.5 mg twice daily at start. After 2 weeks, if necessary, the dose of Captopril would be titrated to 25 mg twice daily, based on subject's response to treatment. The primary efficacy endpoint was reduction in systolic blood pressure (SBP) from baseline to week-8 of treatment. The secondary efficacy endpoints were SBP as well as diastolic blood pressure (DBP) changes at every time-point evaluation and lipid profile improvement. Evaluation of BP was performed every week for 8 weeks of treatment; while of lipid profile at a 4-week interval. Mean SBP at baseline was 149.3+/-5.58 mmHg in Olive group and 148.4+/ 5.56 mmHg in Captopril group; and mean DBPs were 93.9+/-4.51 and 93.8+/-4.88 mmHg, respectively. After 8 weeks of treatment, both groups experienced a significant reduction of SBP as well as DBP from baseline; while such reductions were not significantly different between groups. Means of SBP reduction from baseline to the end of study were -11.5+/-8.5 and -13.7+/-7.6 mmHg in Olive and Captopril groups, respectively; and those of DBP were -4.8+/-5.5 and -6.4+/-5.2 mmHg, respectively. A significant reduction of triglyceride level was observed in Olive group, but not in Captopril group. In conclusion, Olive (Olea europaea) leaf extract, at the dosage regimen of 500 mg twice daily, was similarly effective in lowering systolic and diastolic blood pressures in subjects with stage-1 hypertension as Captopril, given at its effective dose of 12.5-25 mg twice daily. PMID- 21036584 TI - Exercise induced skeletal muscle metabolic stress is reduced after pulmonary rehabilitation in COPD. AB - In COPD, skeletal muscle ATP resynthesis may be insufficient to meet demand during exercise due to excessive anaerobic and reduced oxidative (mitochondrial) energy production, leading to metabolic stress. We investigated the effect of outpatient pulmonary rehabilitation (PR) on the metabolic response (measured by exercise-induced accumulation of plasma ammonia) and determined whether this response predicted functional improvement following PR. 25 subjects with stable COPD [mean (SD) age 67 (8)years and FEV(1) 47 (18)% predicted] performed maximal cycling ergometry before and after PR. Plasma ammonia was measured at rest, during exercise and 2 min post-exercise. Following PR, there were significant increases in peak cycle WR and ISWT performance (Mean (SEM) changes 13.1 (2.0) W and 93 (15) m respectively, p < 0.001). Mean (SEM) rise in plasma ammonia was reduced at peak (Pre vs Post-PR: 29.0 (4.5) vs 20.2 (2.5) MUmol/l, p < 0.05) and isotime (Pre vs Post-PR: 29.0 (4.5) vs 10.6 (1.7) MUmol/l, p < 0.001) exercise. Improvements in exercise performance after PR were similar among subgroups who did versus those who did not show a rise in ammonia at baseline. The results suggest that muscle cellular energy production was better matched to the demands of exercise following PR. We conclude that a pragmatic outpatient PR programme involving high intensity walking exercise results in significant adaptation of the skeletal muscle metabolic response with a reduction in exercise-related metabolic stress. However, the outcome of PR could not be predicted from baseline metabolic response. PMID- 21036585 TI - Lung involvement in hypereosinophilic syndromes. AB - BACKGROUND: Hypereosinophilic syndromes (HES) are a heterogeneous group of conditions that are characterized by tissue-associated eosinophilic inflammation and peripheral eosinophilia. Although clinical and radiologic features associated with most forms of eosinophilic lung diseases are relatively well-described, there is little known regarding lung involvement in HES. The aims of the present study were to ascertain the frequency of pulmonary involvement in HES and define associated clinical and radiologic features. METHODS: We included all patients with HES seen over a 5-year period from 2004 to 2008 and examined their medical records and radiologic studies to obtain relevant data. RESULTS: There were 49 patients (25 males and 24 females) with a median age of 50 years (range, 12-88 years); 18 (37%) had a history of tobacco use. In 12 patients (24%), these pulmonary manifestations were attributable to parenchymal lung involvement with HES. Radiologic manifestations of pulmonary involvement varied but most commonly consisted of patchy ground-glass opacities and consolidation; one patient exhibited numerous pulmonary nodules. Thirteen patients (27%) had asthma including 6 with a new diagnosis of this disorder. Initial treatment usually consisted of corticosteroids but additional therapeutic agents were employed during the clinical course and included hydroxyurea, interferon-alpha, imatinib, and mepolizumab. Most patients with pulmonary involvement with HES improved and no deaths were observed. CONCLUSION: One-quarter of HES patients manifested pulmonary involvement with variable radiologic findings. Asthma was more common in HES than previously reported. Most patients with pulmonary involvement in HES improve with currently available therapies. PMID- 21036586 TI - Luteolin inhibits cytokine expression in endotoxin/cytokine-stimulated microglia. AB - Microglial activation plays a pivotal role in the pathogenesis of neurodegenerative disease by producing excessive proinflammatory cytokines and nitric oxide (NO). Luteolin, a naturally occurring polyphenolic flavonoid antioxidant, has potent anti-inflammatory and neuroprotective properties both in vitro and in vivo. However, the molecular mechanism of luteolin-mediated immune modulation in microglia is not fully understood. In the present study, we report the inhibitory effect of luteolin on lipopolysaccharide (LPS)/interferon gamma (IFN-gamma)-induced NO and proinflammatory cytokine production in rat primary microglia and BV-2 microglial cells. Luteolin concentration-dependently abolished LPS/IFN-gamma-induced NO, tumor necrosis factor alpha (TNF-alpha) and interleukin 1beta (IL-1beta) production as well as inducible nitric oxide synthase (iNOS) protein and mRNA expression. Luteolin exerted an inhibitory effect on transcription factor activity including nuclear factor kappaB (NF-kappaB), signal transducer and activator of transcription 1 (STAT1) and interferon regulatory factor 1 (IRF-1) in LPS/IFN-gamma-activated BV-2 microglial cells. Biochemical and pharmacological studies revealed that the anti-inflammatory effect of luteolin was accompanied by down-regulation of extracellular signal-regulated kinase (ERK), p38, c-Jun N-terminal kinase (JNK), Akt and Src. Further studies have demonstrated that the inhibitory effect of luteolin on intracellular signaling execution and proinflammatory cytokine expression is associated with resolution of oxidative stress and promotion of protein phosphatase activity. Together, these results suggest that luteolin suppresses NF-kappaB, STAT1 and IRF 1 signaling, thus attenuating inflammatory response of brain microglial cells. PMID- 21036589 TI - Protective actions of green tea polyphenols and alfacalcidol on bone microstructure in female rats with chronic inflammation. AB - This study investigated the effects of green tea polyphenols (GTP) and alfacalcidol on bone microstructure and strength along with possible mechanisms in rats with chronic inflammation. A 12-week study using a 2 (no GTP vs. 0.5%, w/v GTP in drinking water)*2 (no alfacalcidol vs. 0.05 MUg/kg alfacalcidol orally, 5*/week) factorial design was employed in lipopolysaccharide (LPS) administered female rats. A group receiving placebo administration was used to compare with a group receiving LPS administration only to evaluate the effect of LPS. Changes in tibial and femoral microarchitecture and strength of femur were evaluated. Difference in expression of tumor necrosis factor-alpha (TNF-alpha) in proximal tibia using immunohistochemistry was examined. Compared to the placebo group, the LPS-administered-only group had significantly lower femoral mass, trabecular volume, thickness and number in proximal tibia and femur, and lower periosteal bone formation rate in tibial shafts but had significantly higher trabecular separation and osteoclast number in proximal tibia and eroded surface in endocortical tibial shafts. Both GTP and alfacalcidol reversed these LPS induced detrimental changes in femur, proximal tibia and endocortical tibial shaft. Both GTP and alfacalcidol also significantly improved femoral strength, while significantly suppressed TNF-alpha expression in proximal tibia. There were significant interactions in femoral mass and strength, trabecular separation, osteoclast number and TNF-alpha expression in proximal tibia. A combination of both showed to sustain bone microarchitecture and strength. We conclude that a protective impact of GTP and alfacalcidol in bone microarchitecture during chronic inflammation may be due to a suppression of TNF-alpha. PMID- 21036588 TI - Lipoic acid stimulates cAMP production via G protein-coupled receptor-dependent and -independent mechanisms. AB - Lipoic acid (LA) is a naturally occurring fatty acid that exhibits anti-oxidant and anti-inflammatory properties and is being pursued as a therapeutic for many diseases including multiple sclerosis, diabetic polyneuropathy and Alzheimer's disease. We previously reported on the novel finding that racemic LA (50:50 mixture of R-LA and S-LA) stimulates cAMP production, activates prostanoid EP2 and EP4 receptors and adenylyl cyclases (AC), and suppresses activation and cytotoxicity in NK cells. In this study, we present evidence that furthers our understanding of the mechanisms of action of LA. Using various LA derivatives, such as dihydrolipoic acid (DHLA), S,S-dimethyl lipoic acid (DMLA) and lipoamide (LPM), we discovered that only LA is capable of stimulating cAMP production in NK cells. Furthermore, there is no difference in cAMP production after stimulation with either R-LA, S-LA or racemic LA. Competition and synergistic studies indicate that LA may also activate AC independent of the EP2 and EP4 receptors. Pretreatment of PBMCs with KH7 (a specific peptide inhibitor of soluble AC) and the calcium inhibitor (Bapta) prior to LA treatment resulted in reduced cAMP levels, suggesting that soluble AC and calcium signaling mediate LA stimulation of cAMP production. In addition, pharmacological inhibitor studies demonstrate that LA also activates other G protein-coupled receptors, including histamine and adenosine but not the beta-adrenergic receptors. These novel findings provide information to better understand the mechanisms of action of LA, which can help facilitate the use of LA as a therapeutic for various diseases. PMID- 21036587 TI - A mechanism by which dietary trans fats cause atherosclerosis. AB - Dietary trans fats (TFs) have been causally linked to atherosclerosis, but the mechanism by which they cause the disease remains elusive. Suppressed transforming growth factor (TGF)-beta responsiveness in aortic endothelium has been shown to play an important role in the pathogenesis of atherosclerosis in animals with hypercholesterolemia. We investigated the effects of a high TF diet on TGF-beta responsiveness in aortic endothelium and integration of cholesterol in tissues. Here, we show that normal mice fed a high TF diet for 24 weeks exhibit atherosclerotic lesions and suppressed TGF-beta responsiveness in aortic endothelium. The suppressed TGF-beta responsiveness is evidenced by markedly reduced expression of TGF-beta type I and II receptors and profoundly decreased levels of phosphorylated Smad2, an important TGF-beta response indicator, in aortic endothelium. These mice exhibit greatly increased integration of cholesterol into tissue plasma membranes. These results suggest that dietary TFs cause atherosclerosis, at least in part, by suppressing TGF-beta responsiveness. This effect is presumably mediated by the increased deposition of cholesterol into cellular plasma membranes in vascular tissue, as in hypercholesterolemia. PMID- 21036590 TI - Effects of long-term supplementation with omega-3 fatty acids on longitudinal changes in bone mass and microstructure in mice. AB - A diet rich in omega-3s has previously been suggested to prevent bone loss. However, evidence for this has been limited by short exposure to omega-3 fatty acids (FAs). We investigated whether a diet enriched in eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) for the entire adult life of mice could improve bone microstructure and strength. Thirty female mice received a diet enriched in DHA or EPA or an isocaloric control diet from 3 to 17 months of age. Changes in bone microstructure were analyzed longitudinally and biomechanical properties were analysed by a three-point bending test. Bone remodelling was evaluated by markers of bone turnover and histomorphometry. Trabecular bone volume in caudal vertebrae was improved by EPA or DHA at 8 months (+26.6% and +17.2%, respectively, compared to +3.8% in controls, P=.01), but not thereafter. Trabecular bone loss in the tibia was not prevented by omega-3 FAs (BV/TV -94%, 93% and -97% in EPA, DHA and controls, respectively). EPA improved femur cortical bone volume (+8.1%, P<.05) and thickness (+4.4%, P<.05) compared to controls. EPA, but not DHA, reduced age-related decline of osteocalcin (-70% vs. -83% in controls, P<.05). EPA and DHA increased leptin levels (7.3+/-0.7 and 8.5+/-0.5 ng ml-1, respectively, compared to 4.5+/-0.9 ng ml-1 in controls, P=.001); however, only EPA further increased IGF-1 levels (739+/-108 ng ml-1, compared to 417+/-58 ng ml-1 in controls, P=.04). These data suggest that long-term intake of omega-3 FA, particularly EPA, may modestly improve the structural and mechanical properties of cortical bone by an increase in leptin and IGF-1 levels, without affecting trabecular bone loss. PMID- 21036591 TI - Generation of and control measures for, e-waste in Hong Kong. AB - While accurately estimating electrical and electronic waste (e-waste) generation is important for building appropriate infrastructure for its collection and recycling, making reliable estimates of this kind is difficult in Hong Kong owing to the fact that neither accurate trade statistics nor sales data of relevant products are available. In view of this, data of e-products consumption at household level was collected by a tailor-made questionnaire survey from the public for obtaining a reasonable e-waste generation estimate. It was estimated that on average no more than 80,443 tones (11.5 kg/capita) of waste is generated from non-plasma and non-liquid crystal display televisions, refrigerators, washing machines, air-conditioners and personal computers each year by Hong Kong households. However, not more than 17% of this is disposed as waste despite a producer responsibility scheme (PRS) not being in place because of the existence of a vibrant e-waste trading sector. The form of PRS control that can possibly win most public support is one that would involve the current e-waste traders as a major party in providing the reverse logistics with a visible recycling charge levied at the point of importation. This reverse logistic service should be convenient, reliable and highly accessible to the consumers. PMID- 21036592 TI - Ultrasensitive quantum dots-based DNA detection and hybridization kinetics analysis with evanescent wave biosensing platform. AB - Ultrasensitive DNA detection was achieved using a new biosensing platform based on quantum dots (QDs) and total internal reflection fluorescence, which featured an exceptional detection limit of 3.2 amol of bound target DNA. The reusable sensor surface was produced by covalently immobilizing streptavidin onto a self assembled alkanethiol monolayer of fiber optic probe through a heterobifunctional reagent. Streptavidin served as a versatile binding element for biotinylated single-strand DNA (ssDNA). The ssDNA-coated fiber probe was evaluated as a nucleic acid biosensor through a DNA-DNA hybridization assay for a 30-mer ssDNA, which were the segments of the uidA gene of Escherichia coli and labeled by QDs using avidin-biotin interaction. Several negative control tests revealed the absence of significant non-specific binding. It also showed that bound target DNA could easily be eluted from the sensor surface using SDS solution (pH 1.9) without any significant loss of performance after more than 30 assay cycles. A quantitative measurement of DNA binding kinetics was achieved with high accuracy, indicating an association rate of 1.38*10(6) M(-1) s(-1) and a dissociation rate of 4.67*10(-3) s(-1). The proposed biosensing platform provides a simple, cheap, fast, and robust solution for many potential applications including clinical diagnosis, pathology, and genetics. PMID- 21036593 TI - Single-molecule approaches to characterizing kinetics of biomolecular interactions. AB - Single-molecule fluorescence techniques have emerged as powerful tools to study biological processes at the molecular level. This review describes the application of these methods to the characterization of the kinetics of interaction between biomolecules. A large number of single-molecule assays have been developed that visualize association and dissociation kinetics in vitro by fluorescently labeling binding partners and observing their interactions over time. Even though recent progress has been significant, there are certain limitations to this approach. To allow the observation of individual, fluorescently labeled molecules requires low, nanomolar concentrations. I will discuss how such concentration requirements in single-molecule experiments limit their applicability to investigate intermolecular interactions and how recent technical advances deal with this issue. PMID- 21036594 TI - General anesthesia for cesarean delivery at a tertiary care hospital from 2000 to 2005: a retrospective analysis and 10-year update. AB - BACKGROUND: Complications from general anesthesia for cesarean delivery are a leading cause of anesthesia-related mortality. As a consequence, the overall use of general anesthesia in this setting is becoming less common. The impact and implications of this trend are considered in relation to a similar study performed at our institution 10 years ago. METHODS: The hospital database for all cesarean deliveries performed during six calendar years (January 1, 2000 through December 31, 2005) was reviewed. The medical records of all parturients who received general anesthesia were examined to collect personal details and data pertinent to the indications for cesarean delivery and general anesthesia, mode of airway management and associated anesthetic complications. RESULTS: Cesarean deliveries accounted for 23.65% to 31.51% of an annual total ranging from 8543 to 10091 deliveries. The percentage of cases performed under general anesthesia ranged from 0.5% to 1%. A perceived lack of time for neuraxial anesthesia accounted for more than half of the general anesthesia cases each year, with maternal factors accounting for 11.1% to 42.9%. Failures of neuraxial techniques accounted for less than 4% of the general anesthesia cases. There was only one case of difficult intubation and no anesthesia-related mortality was recorded. CONCLUSION: The use of general anesthesia for cesarean delivery is low and declining. These trends may reflect the early and increasing use of neuraxial techniques, particularly in parturients with co-existing morbidities. A significant reduction in exposure of trainees to obstetric general anesthesia has been observed. PMID- 21036595 TI - Dangers of rapid oxytocin administration in Eisenmenger's Syndrome. PMID- 21036596 TI - Combined spinal-epidural anaesthesia for a woman with Wegener's granulomatosis with subglottic stenosis. PMID- 21036597 TI - Hereditary neuropathy with a liability to pressure palsies presenting as a case of sensory neuropathy following spinal anaesthesia for caesarean delivery. PMID- 21036598 TI - Cortical progenitor expansion, self-renewal and neurogenesis-a polarized perspective. AB - Neural stem and progenitor cells giving rise to neurons in developing mammalian neocortex fall into two principal classes with regard to location of mitosis apical and basal, and into three principal classes in terms of cell polarity during mitosis-bipolar, monopolar, and nonpolar. Insight has been gained into how inheritance of polarized, apical and basal, cell constituents is related to symmetric versus asymmetric divisions of these progenitors, and how this inheritance is linked to their expansion, self-renewal, and neurogenesis. Retention and inheritance of the basal process emerge as key for self-renewal, notably for the monopolar progenitors of prospective gyrencephalic neocortex that undergo asymmetric mitoses at basal locations. The resulting expansion of the neocortex during evolution is proposed to be associated with an increased cone shape of radial units. PMID- 21036599 TI - Reproducibility and validation of tumour stroma ratio scoring on oesophageal adenocarcinoma biopsies. AB - BACKGROUND: Tumour stroma ratio (TSR) in histological sections of resected oesophageal adenocarcinomas proved to be a prognostic factor for patients' survival. The objectives of this study were to assess inter- and intraobserver agreement for TSR scoring on biopsy material and to validate these biopsy results with the results derived from surgical specimens. METHODS: Biopsies and surgical specimens of 91 patients with oesophageal adenocarcinoma were available. TSR was determined on the original haematoxylin-eosin (H&E) tissue sections from primary tumour biopsies. To assess interobserver variation, TSR was scored by three pathologists as 0-25%, 25-50%, 50-75% or 75-100%. A second scoring was done to examine intraobserver variation. The definitive TSR biopsy score was compared with the corresponding resection specimen score. Kappa statistics were applied to evaluate agreement. RESULTS: Biopsies of 10 (11%) patients were rejected because of poor quality. For 81 TSR biopsy scores, interobserver correlations ranged between 0.239 and 0.486 (P < 0.001 for all). By classifying scores into two groups (<50% and >= 50%), interobserver correlations ranged between 0.372 and 0.886 (P < 0.001 for all). Intraobserver agreement was substantial to near perfect (kappa = 0.780-0.848; P < 0.001 for all). Definitive TSR biopsy score showed moderate correlation with TSR scores on surgical specimens (kappa = 0.506), but it was an independent prognostic factor for survival. CONCLUSION: Reproducibility of tumour stroma ratio scoring on oesophageal adenocarcinoma biopsies was good. The ease of TSR scoring on H&E sections together with its correlation with patients' survival may have clinical relevance in this era of neoadjuvant therapy. PMID- 21036600 TI - Induction of senescence markers after neo-adjuvant chemotherapy of malignant pleural mesothelioma and association with clinical outcome: an exploratory analysis. AB - The aim of this study was to assess the induction of senescence markers versus apoptosis pathways in malignant pleural mesothelioma (MPM) tumour samples before and after neo-adjuvant platinum-based chemotherapy and to investigate their relationship with clinical outcome. Specific senescence pathways were assessed by quantifying the expression of p21 and plasminogen activator inhibitor-1 (PAI-1) for the p21-p53 pathway, IGFBP7 for the IGF pathway and ALDH1A3 for the IFN pathway. p21 and PAI-1 expression were also assessed by immunohistochemistry. In addition, beta-galactosidase activity staining at pH 6.0 was performed. Apoptosis was determined by TUNEL assay. Clinical outcome was assessed by modified RECIST criteria, progression-free and overall survival. In a training set (n=9 patients) paired comparison demonstrated a significant increase in p21 (p<0.05), PAI-1 (p<0.01) and apoptosis (p<0.01) after neo-adjuvant chemotherapy. The patients with the highest increase in PAI-1 had stable disease, whilst patients with little change in senescence markers accompanied by a high increase in apoptosis had an objective response after chemotherapy. The hypothesis that stable disease might be associated with an increase in senescence markers was confirmed in a tissue microarray (n=26 patients) using p21 and PAI-1 immunohistochemistry as readouts. For patients where survival and time to progression data were available, increased PAI-1 levels were significantly associated with a worst outcome. Our results demonstrate induction of senescence markers by neo-adjuvant chemotherapy in a proportion of patients with MPM and its potential association with a poor outcome. PMID- 21036601 TI - Improved 1,3-propanediol production with hemicellulosic hydrolysates (corn straw) as cosubstrate: Impact of degradation products on Klebsiella pneumoniae growth and 1,3-propanediol fermentation. AB - To improve 1,3-propanediol (1,3-PD) production by an economic and efficient approach, hemicellulosic hydrolysates (HH) used as cosubstrate resulted in more biomass and higher reducing power for 1,3-PD production. The effects of primary degradation products such as individual sugars (xylose, glucose, mannose, arabinose and galactose) and major inhibitors (furfural, acetate and formate) on the Klebsiella pneumoiae growth and 1,3-PD production were investigated in this study. Xylose and mannose could efficiently promote the 1,3-PD production and cell growth. Furfural (0.28 g/l) and sodium acetate (1.46 g/l) in low concentration were not inhibitory to Klebsiella pneumoniae, rather they have stimulatory effect on the growth and 1,3-PD biosynthesis, especially the acetate. In fed-batch fermentation with HH as cosubstrate, the final 1,3-PD production, conversion from glycerol and productivity were 71.58 g/l, 0.65 mol/mol and 1.93 g/l/h, respectively, which were 17.8%, 25.0% and 17.7% higher than that from glycerol alone. PMID- 21036602 TI - Production of levulinic acid from steam exploded rice straw via solid superacid, S2O8(2-)/ZrO2-SiO2-Sm2O3. AB - In this study, solid superacid was employed to catalyze the decomposition of steam exploded rice straw (SERS) for the production of levulinic acid, a versatile platform chemical. The results revealed that solid superacid, S(2)O(8)(2-)/ZrO(2)-SiO(2)-Sm(2)O(3), could be used as a substitute for homogenous acid to catalyze the production of LA from SERS and LA yield increased with the addition of solid superacid. It was also found that steam explosion combined with superfine grinding of rice straw could effectively increase LA yield for reducing particle size of rice straw and enhancing the accessibility of cellulose. Under optimal conditions of 200 degrees C, 10 min, 13.3% of solid superacid to pretreated rice straw, and 1:15 of solid-liquid ratio, LA yield of the superfine grinding SERS was 70% of the theoretical yield, which was equivalent with the homogeneous acid-catalyzed production of LA. PMID- 21036603 TI - Pretreatment and enzymatic hydrolysis of wheat straw (Triticum aestivum L.)--the impact of lignin relocation and plant tissues on enzymatic accessibility. AB - Wheat straw is a potential feedstock for bioethanol production. This paper investigates tissues from whole internode sections subjected to hydrothermal pretreatment at 185 degrees C and subsequent enzymatic hydrolysis up to 144 h. Analyses revealed an increase in surface lignin as hydrolysis progressed, which could be coupled to the gradual decrease in hydrolysis rate over time. The data support the hypothesis of lignin extraction from the cell wall matrix during pretreatment and deposition as droplets upon cooling. These droplets are assumed to accumulate during enzymatic hydrolysis. Additionally, after 144 h of enzymatic hydrolysis the cortex had vanished, exposing the heavier lignified vascular tissue. Accumulation of lignin droplets and exposure of residual lignin could be part of the explanation for the decreasing hydrolysis rate. Flattening of macrofibrils after pretreatment together with more indentations on the surfaces was also observed, possibly caused by a proposed synergistic effect of cellobiohydrolases and endoglucanases. PMID- 21036604 TI - Shewanella oneidensis in a lactate-fed pure-culture and a glucose-fed co-culture with Lactococcus lactis with an electrode as electron acceptor. AB - Bioelectrochemical systems (BESs) employing mixed microbial communities as biocatalysts are gaining importance as potential renewable energy, bioremediation, or biosensing devices. While we are beginning to understand how individual microbial species interact with an electrode as electron donor, little is known about the interactions between different microbial species in a community: sugar fermenting bacteria can interact with current producing microbes in a fashion that is either neutral, positively enhancing, or even negatively affecting. Here, we compare the bioelectrochemical performance of Shewanella oneidensis in a pure-culture and in a co-culture with the homolactic acid fermenter Lactococcus lactis at conditions that are pertinent to conventional BES operation. While S. oneidensis alone can only use lactate as electron donor for current production, the co-culture is able to convert glucose into current with a comparable coulombic efficiency of ~17%. With (electro)-chemical analysis and transcription profiling, we found that the BES performance and S. oneidensis physiology were not significantly different whether grown as a pure- or co culture. Thus, the microbes worked together in a purely substrate based (neutral) relationship. These co-culture experiments represent an important step in understanding microbial interactions in BES communities with the goal to design complex microbial communities, which specifically convert target substrates into electricity. PMID- 21036605 TI - Production of metabolites in the biodegradation of phenanthrene, fluoranthene and pyrene by the mixed culture of Mycobacterium sp. and Sphingomonas sp. AB - The effects of the mixed culture of Mycobacterium sp. strain A1-PYR and Sphingomonas sp. strain PheB4 on the degradation characteristics of single polycyclic aromatic hydrocarbon were investigated. In the mixed bacterial culture, phenanthrene, fluoranthene and pyrene were degraded by 100% at Day 3, 71.2% and 50% at Day 7, respectively. Compared to their respective pure cultures, the degradation of phenanthrene and fluoranthene decreased, but that of pyrene increased significantly. Based on GC-MS analysis, eight and six new metabolites were produced from the biodegradation of phenanthrene and fluoranthene, respectively, while only two new metabolites were formed from pyrene. To our knowledge, this is the first report that the mixed bacterial culture could increase the diversity of metabolites from PAH, but the diverse metabolite pattern was not necessarily beneficial to the degradation of the recalcitrant PAH. The enhancement on pyrene degradation was possibly attributed to the rapid growth of strain PheB4. PMID- 21036606 TI - Conversion of biomass into 5-hydroxymethylfurfural using solid acid catalyst. AB - 5-Hydroxymethylfurfural (HMF) was produced from monosaccharide (fructose and glucose), polysaccharide (inulin) and the Jerusalem artichoke juice by a simple one-pot reaction including hydrolysis and dehydration using solid acid under mild condition. Hydrated niobium pentoxide (Nb(2)O(5).nH(2)O(2)) after pretreatment showed high catalytic activities for dehydration of mono- and polysaccharide to HMF at 433 K in water-2-butanol (2:3 v/v) biphasic system, giving high HMF yield of 89% and 54% from fructose and inulin, respectively. The HMF yield was up to 74% and 65% when inulin and Jerusalem artichoke juice were hydrolyzed by exoinulinase. The solid acid made the process environment-friendly and energy efficient to convert carbohydrates into bio-fuels and platform chemicals. PMID- 21036607 TI - Thermodynamic analysis of lignocellulosic biofuel production via a biochemical process: guiding technology selection and research focus. AB - The aim of this paper is to present an exergy analysis of bioethanol production process from lignocellulosic feedstock via a biochemical process to asses the overall thermodynamic efficiency and identify the main loss processes. The thermodynamic efficiency of the biochemical process was found to be 35% and the major inefficiencies of this process were identified as: the combustion of lignin for process heat and power production and the simultaneous scarification and co fermentation process accounting for 67% and 27% of the lost exergy, respectively. These results were also compared with a previous analysis of a thermochemical process for producing biofuel. Despite fundamental differences, the biochemical and thermochemical processes considered here had similar levels of thermodynamic efficiency. Process heat and power production was the major contributor to exergy loss in both of the processes. Unlike the thermochemical process, the overall efficiency of the biochemical process largely depends on how the lignin is utilized. PMID- 21036608 TI - Vermistabilization of primary sewage sludge. AB - An integrated composting-vermicomposting process has been developed for utilization of primary sewage sludge (PSS). Matured vermicompost was used as bulking material and a source of active microbial culture during aerobic activated composting (AAC). AAC resulted in sufficient enrichment of bulking material with organic matter after 20 cycles of recycling and mixing with PSS and produced materials acceptable for vermicomposting. Vermicomposting caused significant reduction in pH, volatile solids (VS), specific oxygen uptake rate (SOUR), total organic carbon (TOC), C/N ratio and pathogens and substantial increase in electrical conductivity (EC), total nitrogen (TN) and total phosphorous (TP) as compared to compost. Environmental conditions and stocking density have profound effects on vermicomposting. Temperature of 20 degrees C with high humidity is favorable environmental condition for vermicomposting employing Eisenia fetida. Favorable stocking density range for vermiculture is 0.5-2.0 kg m(-2) (optimum: 0.5 kg m(-2)) and for vermicomposting is 2.0-4.0 kg m( 2) (optimum: 3.0 kg m(-2)), respectively. PMID- 21036609 TI - Potent and highly selective DP1 antagonists with 2,3,4,9-tetrahydro-1H-carbazole as pharmacophore. AB - We discovered that the introduction of a methyl group to the benzylic position of the N-benzyl group in lead compound 1a has a dramatic effect on improving the binding selectivity of this ligand for the prostanoid receptors DP1 (receptor for prostaglandin D(2)) as compared to TP (receptor for thromboxane A(2)). Based on this discovery, we have synthesized a series of potent and highly selective DP1 antagonists. Among them, compound 1h was identified as a highly selective DP1 antagonist with excellent overall properties. It has a K(i) of 0.43 nM to DP1 in binding assay and an IC(50) of 2.5 nM in the DP1 functional assay. Its selectivity for DP1 over TP (the most potent receptor after DP1) exceeds 750-fold based on both binding and functional assays. These properties make 1h a very potent and highly selective DP1 receptor antagonist suitable for investigating the biological functions of DP1 in normal physiology and models of disease. PMID- 21036610 TI - An inhibitor-like binding mode of a carbonic anhydrase activator within the active site of isoform II. AB - The 2,4,6-trimethylpyridinium derivative of histamine is an effective activator of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1). However, unlike other CA activators, which bind at the entrance of the active site cavity, an X-ray crystal structure of hCA II in complex with the 1-[2-(1H-imidazol-4-yl)-ethyl] 2,4,6-trimethylpyridinium salt evidenced a binding mode never observed before either for activators or inhibitors of this enzyme, with the 2,4,6 trimethylpyridinium ring pointing towards the metal ion deep within the enzyme cavity, and several strong hydrophobic interactions stabilizing the adduct. Indeed, incubation of the activator with the enzyme for several days leads to potent inhibitory effects. This is the first example of a CA activator which after a longer contact with the enzyme behaves as an inhibitor. PMID- 21036611 TI - Novel and efficient synthesis and antifungal evaluation of 2,3-functionalized cholestane and androstane derivatives. AB - Synthetic modifications of cholesterol and other traditional steroid molecules have become a promising area for the exploration and development of novel antifungal agents, especially with respect to the development of fatty-acid esters of steroids. In addition, 2,3-functionalized steroids are also compounds with potentially interesting biological properties and proper functionalization of 2,3-steroids can lead to the development of efficient syntheses of building blocks for novel fatty-acid esters of steroids. In this Letter, we outline a novel and efficient approach to the synthesis of 2,3-functionalized cholestane and androstane derivatives and present their promising preliminary antifungal activities against a number of fungal species. PMID- 21036612 TI - 1,2,3-triazolyl amino acids as AMPA receptor ligands. AB - The central nervous system glutamate receptors are an important target for drug discovery. Herein we report initial investigations into the synthesis and glutamate receptor activity of 1,2,3-triazolyl amino acids. Two compounds were found to be selective AMPA receptor ligands, which warrant further investigation. PMID- 21036613 TI - Synthesis and in vitro inhibitory activity of matrine derivatives towards pro inflammatory cytokines. AB - Matrine, a sophora alkaloid, exhibited good anti-inflammation effects in our previous report. In the present study, a series of matrine derivatives were synthesized via classical Michael addition. Biological studies showed that the synthetic derivatives had good inhibitory effect towards TNF-alpha production and NFkappaB transcriptional activity. The introduction of various amino groups to the keto beta position could improve the biochemical profile, resulting in the identification of more potent derivates, such as 1f, with higher inhibitory activity than both matrine and sophoramine. PMID- 21036614 TI - Stage migration and therapy modification after thoracoscopic internal mammary lymph node dissection in breast cancer patients. AB - Although internal mammary lymph node (IMN) status is a major prognostic factor in breast cancer, it is not routinely assessed. To evaluate the impact of IMN status on staging and treatment of breast cancer, we enrolled 50 consecutive patients with inner or central tumors who received IMN dissection by video-assisted thoracoscopic surgery (VATS) after breast surgery. Of the 50 patients, 20 (40%) had IMN metastases. Of the 20 patients, 6 (12%) were upstaged from N0 to N2b and 5 (10%), 3 (6%) and 6 patients (12%) were upstaged from N1a, N2a, and N3a, respectively, to N3b. Because of the upstaging, 6 patients (12%) with only IMN metastases received more aggressive adjuvant chemotherapy. Because the whole IMN chain was removed in all patients, radiotherapy on IMN field was not required in our cohort independent of IMN status. In conclusion, VATS IMN dissection might lead to stage migration and therapy modification. PMID- 21036615 TI - Sagittal and frontal lower limb joint moments during stair ascent and descent in young and older adults. AB - Stair negotiation is an essential skill required for independent mobility, and is described by older adults as a challenging task that is associated with high fall risk. Little is known about the age-related changes in joint kinetics and the relative contribution of lower limb joint moments during stair negotiation. This study characterized lower extremity joint kinetics and their variability associated with stair ascent and descent in young and older adults. Twenty three young and 32 older adults (>55 years) participated. Three dimensional, bilateral gait analysis provided ankle, knee, and hip moment profiles, which in the sagittal plane were summed to provide the support moment. In addition, intra- and inter-subject coefficients of variation were calculated for ensemble averaged curves. Age-related differences were found in the magnitudes of the moment contributions during event transitions for stair ascent and descent. Within groups, the moment profiles were generally consistent. Ankle and knee moments predominantly contributed to extensor support in the sagittal plane. In the frontal plane, proximal joint abductor moments maintained lateral stability and were larger at the hip in older adults. Understanding age-related alterations in movement control during functional tasks can help inform the rehabilitation management and assessment of patient populations. PMID- 21036616 TI - Evolution of a new signal transduction pathway in Candida albicans. AB - The evolution of new signal transductions pathways is poorly understood. Here I present a rare glimpse into the evolution of one such pathway, namely the white cell pheromone response pathway in Candida albicans. In this pathway, the upper portion has been derived intact from the ancestral pathway for mating, the targeted transcription factor from an ancestral filamentation or biofilm pathway, and the upregulated genes from an ancestral biofilm pathway. Each component of this pathway, therefore, has been derived from a conserved pathway. I suggest that the evolution of this new pathway provides one possible paradigm for the evolution of other signal transduction pathways in new cell types. PMID- 21036617 TI - A randomised controlled trial investigating the effect of posterior capsular stripping on knee flexion and range of motion in patients undergoing primary knee arthroplasty. AB - Increasing knee flexion following total knee arthroplasty (TKA) has become an important outcome measure. Surgical technique is one factor that can influence knee motion. In this study, it was hypothesised that stripping of the posterior knee capsule could improve flexion and range of motion (ROM) following TKA. Patients who were undergoing TKA were prospectively randomised into two groups - one group (62 patients) were allocated stripping of the posterior knee capsule (PCS), the other group (66 patients) no stripping (no-PCS). The primary outcome was change in flexion and ROM compared to pre-operative measurements at three time points; after wound closure, 3 months and 1 year post-operatively. Secondary outcomes were absolute measurements of flexion, extension, ROM and complications. All operations were performed by a single surgeon using the same implant and technique. All patients received identical post-operative rehabilitation. There was a significant gain in flexion after wound closure in the PCS group (p=0.022), however there was no significant difference at 3 months or 1 year post operatively. Absolute values of extension (p=0.008) and flexion (p=0.001) 3 months post-operatively were significantly reduced for the PCS group. The absolute value of ROM was significantly higher for the no-PCS group at 3 months (p=0.0002) and 1 year (p=0.005).There were no significant difference in the rate of complications. Posterior capsular stripping causes a transient increase in flexion that does not persist post-operatively. We do not recommend routine stripping of the posterior knee capsule in patients undergoing TKA. PMID- 21036618 TI - Comparative outcome analysis of malpositioned and properly positioned fixation groups after hamstring autograft ACL reconstruction with femoral cross-pin fixation. AB - Anterior cruciate ligament (ACL) reconstruction using soft tissue grafts has been gaining in popularity. Cross-pin fixation is used frequently, and its principle of fixation is an expansion mechanism. However, some malpositioned cases have been reported, and these malpositions may cause poor outcomes. Our aim was to compare the stability and clinical results between malpositioned and properly positioned cases. From November 2003 to December 2007, 41 patients were enrolled in this study. We divided these patients into malpositioned and properly positioned subgroups. The malpositioned group was defined by the presence of any finding among the following: posteriorly directed cross-pin to the posterior condylar line upon axial imaging, breakage upon coronal imaging, and outside positioned cross-pin to the distal femoral posterior cortex upon sagittal imaging. We compared clinical and stability results between the two groups. Twenty-three patients were included in the properly positioned group, and 18 in the malpositioned group. The intra-class correlation coefficient for the intra- and inter-rater agreement ranged from 0.88 to 0.93 (0.88, 0.91, 0.91, and 0.93). No significant differences were found between the two groups in the stability assessment using a KT-2000 arthrometer and pivot-shift test (P=0.93 and 0.78, respectively). No significant differences were found between the two groups in the clinical knee scales (Ps=0.08-0.93). This study showed that some malpositions can occur with cross-pin femoral fixation. However, we obtained comparable good outcomes regardless of the fixation strategies if the initial fixation was correct. PMID- 21036619 TI - Development of a multicomponent kinetic assay of the early enzymes in the Campylobacter jejuni N-linked glycosylation pathway. AB - The human pathogen Campylobacter jejuni possesses a general N-linked glycosylation system that is known to play a role in pathogenicity; however, a detailed understanding of this role remains elusive. A considerable hindrance to studying bacterial N-glycosylation in vivo is the absence of small molecule inhibitors to reversibly control the process. This report describes a pathway screening assay that targets the early enzymes of C. jejuni N-glycan biosynthesis that would enable identification of inhibitors to the first four steps in the pathway. The assay includes PglF, PglE, PglD, PglC, and PglA; the enzymes involved in the biosynthesis of an undecaprenyl diphosphate-linked disaccharide and monitors the transfer of [3H]GalNAc from the hydrophilic UDP-linked carrier to the lipophilic UndPP-diNAcBac (2,4-diacetamido-2,4,6-trideoxyglucose). The optimized assay has a Z'-factor calculated to be 0.77, indicating a robust assay suitable for screening. The diacylglycerol kinase from Streptococcus mutans, which provides a convenient method for phosphorylating undecaprenol, has been included in a modified version of the assay thereby allowing the screen to be conducted with entirely commercially available substrates. PMID- 21036620 TI - Development of novel bisubstrate-type inhibitors of histone methyltransferase SET7/9. AB - Histone modification, for example, by histone deacetylase (HDAC) and histone lysine methyltransferase (HMT), plays an important role in regulating gene expression. To obtain novel inhibitors as tools for investigating the physiological function of members of the HMT family, we designed and synthesized novel inhibitors, which are amine analogues of adenosylmethionine (AdoMet; the cofactor utilized in the methylation reaction) bearing various alkylamino groups coupled via an ethylene linker. The inhibitory activities of these compounds towards SET7/9, an HMT, were evaluated. It was found that introduction of an alkylamino group increased the inhibitory activity. PMID- 21036621 TI - Steroid conjugates: Synthesis and preliminary biological testing of pro juvenoids. AB - A series of 10 new pro-juvenoids (juvenogens, insect hormonogenic compounds, pro drug-like agents) was synthesized using isomeric synthetic juvenoids (insect juvenile hormone analogs) and steroid molecules as patterns modifying parts of the complex hormonogenic molecules. In addition, several new synthons were prepared, which were required by the designed synthetic protocol to achieve the target molecules. These pro-juvenoids were subjected to the topical screening tests and to the drinking assays on the red firebug (Pyrrhocoris apterus), a convenient model laboratory phytophagous insect. Simple and efficient synthetic procedures for the preparation of the target pro-juvenoids and their synthons are presented. Furthermore, the biological activity of the pro-juvenoids in comparison with the activity of their parent juvenoids and that of several commercially available agents is demonstrated. Juvenoids and pro-juvenoids may replace toxic insecticides persistent in the insect pest control because they have no adverse effects on non-target organisms and/or human. PMID- 21036622 TI - Implication of the disulfide bridge in trypsin inhibitor SFTI-1 in its interaction with serine proteinases. AB - Fourteen monocyclic analogues of trypsin inhibitor SFTI-1 isolated from sunflower seeds were synthesized by the solid-phase method. The purpose of this work was to establish the role of a disulfide bridge present in inhibitor's side chains of Cys3 and Cys11 in association with serine proteinases. This cyclic fragment was replaced by the disulfide bridges formed by l-pencillamine (Pen), homo-l-cysteine (Hcy), N-sulfanylethylglycine (Nhcy) or combination of the three with Cys. As in the substrate specificity the P(1) position of the synthesized analogues Lys, Nlys [N-(4-aminobutyl)glycine], Phe or Nphe (N-benzylglycine) were present, and they were checked for trypsin and chymotrypsin inhibitory activity. The results clearly indicated that Pen and Nhcy were not acceptable at the position 3, yielding inactive analogues, whereas another residue (Cys11) could be substituted without any significant impact on the affinity towards proteinase. On the other hand, elongation of the Cys3 side chain by introduction of Hcy did not affect inhibitory activity, and an analogue with the Hcy-Hcy disulfide bridge was more than twice as effective as the reference compound ([Phe5] SFTI-1) in inhibition of bovine alpha-chymotrypsin. PMID- 21036623 TI - Synthesis, molecular modeling and biological evaluation of guanidine derivatives as novel antitubulin agents. AB - A series of novel chalcone guanidine derivatives (4a-4q) have been designed and synthesized, and their biological activity were also evaluated as potential antiproliferative and antitubulin polymerization inhibitors. Compound 4q showed the most potent biological activity (IC50 = 0.09 +/- 0.01 MUM for MCF-7 and IC50 = 8.4 +/- 0.6 MUM for tubulin), which is comparable to the positive controls. Docking simulation was performed to position compound 4q into the colchicine binding site to determine the probable binding model, which suggested probable inhibition mechanism. PMID- 21036624 TI - Radiochemical synthesis of etomoxir. AB - Sodium 2-{6-(4-chlorophenoxy)hexyl}oxirane-2-carboxylate (Etomoxir) inhibits transport of fatty acids via the carnitine shuttle into mitochondria of muscle cells and prevents long chain fatty acids from providing energy through beta oxidation especially for muscle contraction. The objective of this synthesis is to develop a method for radioiodination of Etomoxir in order to explore its potential in diagnostic metabolic studies and molecular imaging. Thus, a method is described for the radiochemical synthesis and purification of ethyl 2-{6-(4 [(131)I]iodophenoxy)hexyl}oxirane-2-carboxylate (3) and 2-{6-(4-[(131)I]iodo phenoxy)hexyl}oxirane-2-carboxylic acid (4). For the synthesis of these new agents, ethyl 2-{6-(4-bromophenoxy)hexyl}oxirane-2-carboxylate (1) and 2-{6-(4 bromophenoxy)hexyl}oxirane-2-carboxylic acid (2) were refluxed with [(131)I]NaI in the presence of anhydrous acetone at a temperature of 80 degrees C and 90 degrees C for a period of 3-4 hours, respectively. The method of radiolabeling, based on the nucleophilic exchange reaction, resulted in a radiochemical yield of 43% and 67% for compounds 3 and 4, respectively. This paper reports on the labeling of etomoxir with radioiodine as (124)I labeled etomoxir may be of great importance in molecular imaging. PMID- 21036626 TI - Absence of sensory function in the reconstructed anterior cruciate ligament. AB - Cruciate ligaments provide sensory information that cause excitatory as well as inhibitory effects to the activity of the muscles around the knee. The aim of the study was to determine whether these muscular reflexes are reestablished after anterior cruciate ligament (ACL) re-construction. Wire electrodes were inserted during arthroscopy into the normal posterior cruciate ligament (PCL) and the reconstructed ACL in 11 patients who had a successful ACL re-construction 8 months to 12 years earlier. After the anesthesia had subsided, the PCL was stimulated electrically through the electrodes and the sensory threshold was determined. Stimulus amplitudes were increased to 1.5-2.0 times the sensory threshold, and inhibitory reflexes could be elicited from PCL in the quadriceps during active extension and in the hamstrings muscles during active flexion in all patients. Subsequently the ACL re-constructions were stimulated. The sensory threshold was 3.4 times higher in the ACL than in the PCL. Stimulus amplitudes were increased to 1.5-2.0 times the sensory threshold, and a typical inhibitory reflex could be elicited in 9 patients. The latency was the same as for the reflex from the PCL. The stimulus amplitudes necessary to elicit reflexes from the ACL re-constructions were 2, 9 times higher than amplitudes that elicited reflexes from the PCL. Sensation and afferent reflex activity required a much stronger stimulus in the ACL graft compared to normal PCL. We suggest that the reason for this is that the ACL grafts were not reinnervated, and that the reflexes were elicited by spread of stimulus current to the PCL. PMID- 21036625 TI - CXCR1 and CXCR2 are novel mechano-sensors mediating laminar shear stress-induced endothelial cell migration. AB - The migration of endothelial cells (ECs) plays critical roles in vascular physiology and pathology. The receptors CXCR1 and CXCR2, known as G protein coupled receptors which are essential for migratory response of ECs toward the shear stress-dependent CXCL8 (interleukin-8), are potential mechano-sensors for mechanotransduction of the hemodynamic forces. In present study, the mRNA and protein expression of CXCR1 and CXCR2 in EA.hy926 cells was detected by RT-PCR and Western blot analysis under three conditions of laminar shear stress (5.56, 10.02 and 15.27 dyn/cm(2)) respectively. Using a scratched-wound assay, the effects of CXCR1 and CXCR2 were assessed by the percentage of wound closure while CXCR1 and CXCR2 were functional blocked by the CXCL8 receptor antibodies. The results showed that the mRNA and protein expression of CXCR1 and CXCR2 was both upregulated by 5.56 dyn/cm(2) laminar shear stress, but was both downregulated by 15.27 dyn/cm(2). The wound closure was inhibited significantly while cells were treated with those antibodies in all the conditions. It was suggested that CXCR1 and CXCR2 are involved in mediating the laminar shear stress-induced EC migration. Taken together, these findings indicated that CXCR1 and CXCR2 are novel mechano-sensors mediating laminar shear stress-induced EC migration. Understanding this expanded mechanism of laminar shear stress-induced cell migration will provide novel molecular targets for therapeutic intervention in cancer and cardiovascular diseases. PMID- 21036627 TI - Multiple ischemic strokes after transcatheter arterial chemoembolization for hepatocellular carcinoma with a radiographic and pathological correlate. AB - INTRODUCTION: Transcatheter arterial chemoembolization (TACE) is a widely used form of therapy in advanced hepatocellular carcinoma. We report the first pathological data from an autopsy case of multiple cerebral emboli occurring during TACE. METHODS: A Medline search for previous cases of cerebral embolism and TACE revealed 11 other cases. FINDINGS: Multiple microscopic subacute infarcts were found in the cerebrum, midbrain, and cerebellum of our patient on autopsy, but no embolic material was seen. Embolic material was noted in dilated vessels throughout the fibrotic right diaphragm and in the upper lobe of the right lung. Combining the literature search with our patient, the mortality of cerebral embolism after TACE is 25% (n = 12). Intracardiac shunts were seen in 20% of the cases (n = 10). Hyperdense lesions were seen on head CT in 80% of the patients evaluated (n = 10). Chest imaging revealed infiltrate or consolidation in 60% of the cases (n = 5). Pulmonary emboli were reported in 100% of the cases (n = 8). CONCLUSIONS: Cerebral embolism after TACE is devastating. Brain pathology supports embolization of ethiodized oil rather than DC beads as the mechanism of cerebral injury. Further pathological studies are needed to better understand the pathophysiology of this condition. Lung pathology confirmed the presence of embolic material in the distal lung, suggestive of a hepatopulmonary shunt undetectable by current modalities. Evaluation for such shunts with emerging modalities such as TCD with emboli detection may be an area of future research. PMID- 21036628 TI - Primary valvular lipomatous hamartoma: a case report and a collective review of the literature. AB - Cardiac valvular tumors are very infrequent lesions constituting about 10% of the primary cardiac neoplasms. Among the valvular tumors, lipomatous hamartoma represents a very rare and distinct pathological entity. Retrieval of the literature reveals only eight reported cases, and there is lack of information regarding their clinical features. Herein, we describe a patient with a mass on the tricuspid valve detected incidentally and diagnosed to be a "lipomatous hamartoma." To obtain a better understanding of the nature of these unusual lesions, we reviewed the literature and presented their clinicoanatomical characteristics together with diagnostic and therapeutic approaches. PMID- 21036629 TI - Isolated thoracic aortitis: clinicopathological and immunohistochemical study of 11 cases. AB - Isolated thoracic aortitis (ITA) is diagnosed in a variable proportion of patients operated on for dilation/aneurysm of ascending aorta. The etiopathogenesis of ITA remains unclear. We studied 11 cases of ITA in order to determine the role of IgG4-mediated immune responses in its pathogenesis. The series included nine women and two men aged 52-79 years. All patients developed aortic incompetence due to dilation/aneurysm of ascending aorta. None of the patients had a history of IgG4-related disease neither did they develop features of such disease during the follow-up period. The microscopic findings included the presence of lymphoplasmacellular fibrosing infiltrate of varied intensity involving the adventitia and media of aorta. This inflammation was associated with severe medial elastic fiber defects. Obliterative phlebitis of the vasa vasorum was absent. Immunohistochemically, the inflammatory infiltrate comprised T- and B-lymphocytes as well as plasma cells. The plasma cell population was polyclonal with a predominance of IgG-producing cells. In all the cases, IgG4 producing plasma cells were detected. In five cases, the count exceeded 20 cells per high-power field. The IgG4/IgG ratio ranged from 0.07 to 0.98 (median 0.55). In six cases with the ratio >0.50, severe adventitial fibrosis was present. To the best of our knowledge, ours is the first study focused on investigating the role of IgG4-positive plasma cells in the development of ITA. Our results suggest that a subset of ITA may represent aortic manifestation of IgG4-related disease. Further research is necessary in order to clarify this issue. PMID- 21036630 TI - Prospective randomized single-blinded in vitro and ex vivo evaluation of new and reprocessed laparoscopic trocars. AB - BACKGROUND: Reprocessing of single-use medical instruments has been proposed as a mechanism for managing the rising costs of health care. We compared the performance of new and reprocessed laparoscopic trocars. STUDY DESIGN: New and reprocessed laparoscopic trocars were evaluated. Testing consisted of visual and microscopic inspection, force of trocar insertion and removal through a porcine abdominal wall, trocar seal leak rate determination, and testing of blade shield speed. RESULTS: Three hundred twenty-eight reprocessed trocars and 199 new trocars were evaluated. Trocars undergoing force testing were inspected for imperfections. In this group, 28.2% of reprocessed and 3.79% of new trocars manifested some gross or microscopic imperfections (p = 0.063). D12LT trocars (Ethicon) required more force with insertion with reprocessed compared with new trocars (0.021). D5LT (Ethicon) new trocars required more force to remove than reprocessed trocars (p = 0.004). Both the shield cover time and the shield response time were found to be faster in the reprocessed (p = 0.0001) compared with the new trocars. Leak testing performed with probes (4.7 mm and 12.9 mm) in place demonstrated a significantly greater amount of leakage for the reprocessed trocars compared with the new trocars, both before and after insertion of the right-angled instrument (p = 0.0001). CONCLUSIONS: When comparing new and reprocessed trocars, there are significant differences in visual trocar defects, insertion and extraction forces, shield response times, and trocar leak rates for some of the device comparisons. The clinical significance of these changes should be weighed against cost savings and environmental impact. Additional testing is necessary for a better understanding of the impact of trocar reprocessing. PMID- 21036631 TI - Predictors of clinical outcome in acute pulmonary embolism: Correlation of CT pulmonary angiography with clinical, echocardiography and laboratory findings. AB - RATIONALE AND OBJECTIVES: The aims of this study were to retrospectively evaluate whether computed tomographic (CT) parameters were predictors of in-hospital mortality within 30 days of CT imaging and to compare CT parameters with clinical, echocardiographic, and laboratory findings in patients with acute pulmonary embolism (PE). MATERIALS AND METHODS: A total of 122 patients (61 women, 61 men; mean age, 64 +/- 15 years) with CT scans positive for acute PE were reviewed. Two independent readers who were blinded to clinical outcomes scored pulmonary artery obstructions, evaluated cardiovascular measurements, and assessed qualitative findings. Reports of echocardiographic, clinical, and laboratory findings and clinical outcome were reviewed. Results were correlated with patient outcomes using Wilcoxon's rank-sum, chi2, and Student's t tests. Logistic regression analyses were performed to determine predictors of patient outcomes. RESULTS: Thirteen patients (11%) died related to PE within 30 days in the hospital. There were significant differences in the ratio of arterial partial pressure of oxygen to inspired fraction of oxygen and in heart rate between survivors and nonsurvivors (P < .05). No CT or echocardiographic predictor was associated with mortality. CONCLUSIONS: The ratio of arterial partial pressure of oxygen to inspired fraction of oxygen and heart rate strongly predicted mortality due to PE. Neither CT pulmonary angiographic variables nor echocardiography could successfully predict in-hospital mortality in patients with acute PE. PMID- 21036633 TI - The role of retinal regulation of sleep in health and disease. AB - The process of photoentrainment, through the activation of photoreceptor transduction cascades, influences the circadian physiology of many life forms from primitive invertebrates to primates. In humans, a population of intrinsically photosensitive retinal ganglion cells (ipRGC's) is responsible for mediating the circadian rhythm and is susceptible to primary dysfunction affecting this cell population specifically, or disorders influencing light activation of retinal ganglion photoreceptors. The former may arise through cell depletion in conditions such as inherited or acquired optic neuropathies or conditions like Parkinson's disease which may alter retinal dopamine-mediated neurotransmission, and the latter, secondary to common causes of light transmission reduction associated with ageing and cataract. This review examines the current evidence linking ocular pathology and the resultant reduction in retinal phototransduction with circadian disturbances and sleep disorders, with downstream effects on our overall physiological integrity. As our understanding of the effects of light pathways on circadian biology develops, therapeutic modalities based upon the underlying pathophysiological processes are emerging, although the direct measurement, consequences and treatment of relative or absolute ipRGC dysfunction remain to be fully and clearly elucidated in man. PMID- 21036632 TI - CT tumor volume measurement in advanced non-small-cell lung cancer: Performance characteristics of an emerging clinical tool. AB - RATIONALE AND OBJECTIVES: Determine inter- and intraobserver variability of computed tomography (CT) tumor volume measurements in advanced non-small-cell lung cancer (NSCLC) patients treated in a Phase II clinical trial using chest CT. MATERIALS AND METHODS: Twenty-three advanced NSCLC patients with a total of 53 measurable lung lesions enrolled in a Phase II, multicenter, open-label clinical trial of erlotinib were retrospectively studied with institutional review board approval. Two radiologists independently measured the tumor size, volume, and CT attenuation coefficient using commercially available volume analysis software. Concordance correlation coefficients (CCCs) and Bland-Altman plots were used to assess inter- and intraobserver agreement. RESULTS: High CCCs (0.949-0.990) were observed in all types of measurements for interobserver agreement. The 95% limits of agreements for volume, unidimensional, and bidimensional measurements were ( 26.0%, 18.6%), (-23.1%, 24.4%), and (-34.0%, 48.6%), respectively. Volume measurement had slightly higher CCC and narrower 95% limits of agreement compared to uni- and bidimensional measurements. CCCs for intraobserver agreement were high (range, 0.946-0.996) with CCC for volume being slightly higher than CCCs of uni- and bidimensional measurements. The smaller the tumor volume was, the larger the interobserver difference of CT attenuation. Location, morphology, or adjacent atelectasis had no significant impact on inter- or intraobserver variability. CONCLUSION: CT tumor volume measurement in advanced NSCLC patients using clinical chest CT and commercially available software demonstrated high inter- and intraobserver agreement, indicating that the method may be used routinely in clinical practice. PMID- 21036635 TI - A randomised, double-blind, placebo-controlled trial of dolasetron, a 5 hydroxytryptamine 3 receptor antagonist, in patients with fibromyalgia. AB - OBJECTIVE: The purpose of the study was to evaluate the efficacy and safety of dolasetron for symptomatic relief of pain associated with fibromyalgia (FM). METHODS: This prospective, double-blind, placebo-controlled trial randomly assigned 60 patients with FM to receive placebo (n = 31) or dolasetron (n = 29) 12.5mg/d via the intravenous route on 4 days at baseline (M0), 1 month (M1), 2 months (M2) and 3 months (M3) with follow-up to month 12. The primary outcome variable was the reduction in pain intensity measured by visual analogue scale (VAS) between M0 and M3. The secondary outcome variables were patient global impression of change (PGIC), the FM impact questionnaire, assessment of quality of life (SF-36), the hospital anxiety and depression scale, the manual tender point count, and functional symptoms associated with FM. RESULTS: Reduction in pain intensity at M3 was significantly greater in dolasetron-treated patients (p = 0.04, -21.3 on a 0-100 scale) compared with placebo controls (-5.9). More patients in the dolasetron group had >= 30% and >= 50% improvement in pain (42.5% and 28% respectively in the dolasetron group versus 25% and 16% in the placebo group). The PGIC was significantly greater in the dolasetron group at M3 (p = 0.02). The other secondary outcomes failed to reach statistical significance. The most common adverse events were constipation, nausea, dizziness and headache, with no significant differences between the two groups. CONCLUSION: Intermittent IV dolasetron was safe and efficacious for the reduction of pain intensity associated with FM at 3 months. PMID- 21036634 TI - Oral administration of tepoxalin in the horse: a PK/PD study. AB - Tepoxalin is a non-steroidal anti-inflammatory drug with analgesic, anti inflammatory, and antipyretic properties and has been recently introduced into veterinary medicine. The aim of this study was to evaluate the pharmacokinetic/pharmacodynamic (PK/PD) profile of tepoxalin to assess whether it would be suitable for clinical use in horses. Six female fasting/fed horses were given 10mg/kg tepoxalin orally in a cross-over study. After administration, tepoxalin underwent rapid and extensive hydrolytic conversion to its carboxylic acid metabolite RWJ-20142. In animals that had been fed, the plasma concentrations of tepoxalin were undetectable, whereas in fasting animals they were close to the limit of quantification of the method. No differences between the fasting/fed groups in RWJ-20142 plasma concentrations were shown. Tepoxalin showed a strong and long-lasting ex vivo inhibitory activity against cyclooxygenase (COX)-1, mainly due to its main metabolite RWJ-20142. Tepoxalin and RWJ-20142 do not seem to possess either COX-2 or 5-lipoxygenase inhibitory activity in the horse. These features suggest that the drug is a selective COX-1 inhibitor in horses, with no significant anti-inflammatory activity. Thus, its long term use in equine practice could be of concern. PMID- 21036636 TI - Selective detection of hyperpolarized NMR signals derived from para-hydrogen using the Only Para-hydrogen SpectroscopY (OPSY) approach. AB - A new family of NMR pulse sequences is reported for the recording of para hydrogen enhanced NMR spectra. This Only Para-hydrogen SpectroscopY (OPSY) approach uses coherence selection to separate hyperpolarized signals from those of fully relaxed and thermally equilibrated protons. Sequence design, performance, practical aspects and applicability to other hyperpolarization techniques are discussed. PMID- 21036637 TI - A portable Halbach magnet that can be opened and closed without force: the NMR CUFF. AB - Portable equipment for nuclear magnetic resonance (NMR) is becoming increasingly attractive for use in a variety of applications. One of the main scientific challenges in making NMR portable is the design of light-weight magnets that possess a strong and homogeneous field. Existing NMR magnets can provide such magnetic fields, but only for small samples or in small regions, or are rather heavy. Here we show a simple yet elegant concept for a Halbach-type permanent magnet ring, which can be opened and closed with minimal mechanical force. An analytical solution for an ideal Halbach magnet shows that the magnetic forces cancel if the structure is opened at an angle of 35.3 degrees relative to its poles. A first prototype weighed only 3.1 kg, and provided a flux density of 0.57 T with a homogeneity better than 200 ppm over a spherical volume of 5mm in diameter without shimming. The force needed to close it was found to be about 20 N. As a demonstration, intact plants were imaged and water (xylem) flow measured. Magnets of this type (NMR-CUFF = Cut-open, Uniform, Force Free) are ideal for portable use and are eminently suited to investigate small or slender objects that are part of a larger or immobile whole, such as branches on a tree, growing fruit on a plant, or non-metallic tubing in industrial installations. This new concept in permanent-magnet design enables the construction of openable, yet strong and homogeneous magnets, which aside from use in NMR or MRI could also be of interest for applications in accelerators, motors, or magnetic bearings. PMID- 21036638 TI - Primary perivascular epithelioid cell tumor of the bladder. AB - The perivascular epithelioid cell family of tumors includes angiomyolipoma, clear cell "sugar" tumor of the lung, lymphangioleiomyomatosis, and clear cell myomelanocytic tumor of the falciform ligament/ligamentum teres. Less frequently, perivascular epithelioid cell tumors arise in various other locations throughout the body including soft tissue, bone, and visceral organs. We report a case of a 23-year-old man who presented with 2-month history of frequent micturition and odynuria. Based on clinical examination, ultrasound computed tomography imaging, surgical operation, and histopathologic studies, a definitive diagnosis was made. Further characteristic images and pathology of this disease are discussed. PMID- 21036639 TI - Gangliocytic paraganglioma: a rare case with metastases of all 3 elements to liver and lymph nodes. AB - Gangliocytic paragangliomas are a rare but well-described neuroendocrine tumor with a proclivity for the duodenal area. It is usually a locally infiltrative lesion with a good prognosis. Rare cases that spread to lymph nodes have been documented. A 52-year-old female was found to have a duodenal tumor, enlarged regional lymph nodes, and multiple small nodules in the liver. The duodenal tumor was a classic triphasic gangliocytic paraganglioma. Two regional lymph nodes and one of the nodules in the liver were noted to contain all 3 elements constituting a gangliocytic paraganglioma. This is the second case of gangliocytic paraganglioma with liver spread and is also noteworthy because of the presence of all 3 elements in the metastases. The presence of lymph node and liver metastases should not result in overtreatment as such behavior is not necessarily fraught with a bad clinical outcome. It is probably best to regard such cases as having "uncertain malignant potential" and advocate careful follow-up. PMID- 21036640 TI - Acquired cystic disease-associated renal cell carcinoma with sarcomatoid change and rhabdoid features. AB - Acquired cystic disease (ACD)-associated renal cell carcinoma (RCC) is a recently described entity. To the best of our knowledge, there are no reports of ACD associated RCC with sarcomatoid and rhabdoid changes. In this article, we present the first case of such a tumor. A 56-year-old Japanese man has received long-term hemodialysis and had a history of right renal cancer. Following the discovery of metastatic cancer in the thoracic wall, detailed imaging studies revealed a mass in the left kidney. The histologic examination of the left renal tumor showed ACD associated RCC with sarcomatoid change and rhabdoid features. Immunohistochemically, intracytoplasmic globular inclusions in rhabdoid cells were positive for vimentin and cytokeratin CAM5.2. The G-band karyotype showed the following changes: 46, X, +X. -Y[1]/43, idem, add(2)(q31), -6, -9, -14, -15, +16, -22, +mar1[6]/46, XY[2]/abnormal cell[11]. In conclusion, pathologists and urologists should be aware that rhabdoid features may occur in ACD-associated RCC and that the loss of chromosomes 9 and 14 may occur during the process of sarcomatoid change in ACD-associated RCC. PMID- 21036641 TI - DFG-in and DFG-out homology models of TrkB kinase receptor: induced-fit and ensemble docking. AB - Kinases from the Trk family are important for the regulation of development and for the correct functioning of the neural system. Deregulation (over-expression) of Trks leads to survival and proliferation of different human cancers. Therefore, development of inhibitors for Trks that can disrupt the signal pathway of Trks could lead to cure against cancer as well as to nociception. Homology models built by YASARA have been used as targets for docking various libraries of known Trk inhibitors. The receptor plasticity was compensated with induced fit docking and/or ensemble docking. It was determined that DFG-in and DFG-out conformational states of TrkB kinase must be taken into account in order to get more reasonable relationships between the docking score and the activity measured by pIC50 or the corresponding ligands. PMID- 21036642 TI - Use of bisphosphonates to treat severe idiopathic hypercalcaemia in a young Ragdoll cat. AB - A 3-year-old Ragdoll cat was referred for investigation of polyuria, polydipsia, vomiting, weight loss and hypercalcaemia. Serum biochemical abnormalities included total and ionised hypercalcaemia and hypophosphataemia. Following clinical investigations a diagnosis of idiopathic hypercalcaemia was made. Because of the severity of the hypercalcaemia and the associated clinical signs, treatment for hypercalcaemia was commenced with pamidronate. Major electrolyte abnormalities were detected but, remarkably, were accompanied by minimal clinical signs. The cat was subsequently treated with oral alendronate and is clinically normal 15 months later. Reports of the use of bisphosphonates in cats are limited and close monitoring of patients is recommended. PMID- 21036643 TI - Disseminated Mycobacterium avium subspecies infection in a cat. AB - An 18-month-old neutered male domestic shorthair cat, domiciled in the southwest of France, was first presented having suffered for a few days from dysorexia and vomiting. Abdominal palpation revealed lymph node enlargement. Cytological examinations of a fine needle aspirate demonstrated granulomatous inflammation with many non-staining elements consistent with mycobacteria. Diagnosis was confirmed by culture and polymerase chain reaction and Mycobacterium avium subspecies was isolated. Treatment was initiated with marbofloxacin, rifampicin and cefoxitin. There was a rapid clinical improvement. The cat suddenly died 2 months later. The main hypothesis is the administration of an inappropriate combination therapy that leads to the development of mycobacterial resistance. A volvulus and acute peritonitis secondary to the significant enlargement of a mesenteric lymph node were present at necropsy. Histopathological analysis of mesenteric lymph node, liver and spleen revealed multicentric granulomatous and severely necrotic lesions with numerous Ziehl-Neelsen positive intracytoplasmic elements. PMID- 21036644 TI - [Quality of working life of health professionals]. PMID- 21036645 TI - The utility of rapid antigen detection testing for the diagnosis of streptococcal pharyngitis in low-resource settings. AB - OBJECTIVES: To evaluate the utility of rapid antigen detection testing (RADT) for the diagnosis of group A streptococcal (GAS) pharyngitis in pediatric outpatient clinics in four countries with varied socio-economic and geographic profiles. METHODS: We prospectively evaluated the utility of a commercial RADT in children aged 2-12 years presenting with symptoms of pharyngitis to urban outpatient clinics in Brazil, Croatia, Egypt, and Latvia between August 2001 and December 2005. We compared the performance of the RADT to culture using diagnostic and agreement statistics, including sensitivity, specificity, and positive and negative predictive values. The Centor scores for GAS diagnosis were used to assess the potential effect of spectrum bias on RADT results. RESULTS: Two thousand four hundred and seventy-two children were enrolled at four sites. The prevalence of GAS by throat culture varied by country (range 24.5-39.4%) and by RADT (range 23.9-41.8%). Compared to culture, RADT sensitivity ranged from 72.4% to 91.8% and specificity ranged from 85.7% to 96.4%. The positive predictive value ranged from 67.9% to 88.6% and negative predictive value ranged from 88.1% to 95.7%. CONCLUSIONS: In limited-resource regions where microbiological diagnosis is not feasible or practical, RADTs should be considered an option that can be performed in a clinic and provide timely results. PMID- 21036646 TI - Diagnostic strategy for patients with hypogammaglobulinemia in rheumatology. AB - The discovery of hypogammaglobulinemia, which is defined as a plasmatic level of immunoglobulin (Ig) under 5 g/L is rare in clinical practice. However, the management of immunodepressed patients in rheumatology, sometimes due to the use of immunosuppressive treatments such as anti-CD20 in chronic inflammatory rheumatisms, increases the risk of being confronted to this situation. The discovery of hypogammaglobulinemia in clinical practice, sometimes by chance, must never be neglected and requires a rigorous diagnosis approach. First of all, in adults, secondary causes, in particular lymphoid hemopathies or drug-related causes (immunosuppressors, antiepileptics) must be eliminated. A renal (nephrotic syndrome) or digestive (protein-losing enteropathy) leakage of Ig is also possible. More rarely, it is due to an authentic primary immunodeficiency (PID) discovered in adulthood: common variable immunodeficiency (CVID) which is the most frequent form of PID, affects young adults between 20 and 30 years and can sometimes trigger joint symptoms similar to those in rheumatoid arthritis; or Good syndrome, which associates hypogammaglobulinemia, thymoma and recurrent infections around the age of 40 years. In most cases, after confirming hypogammaglobulinemia on a second test, biological examinations and thoracic abdominal-pelvic CT scan will guide the diagnosis, after which the opinion of a specialist can be sought depending on the findings of the above examinations. At the end of this review, we provide a decision tree to guide the clinician confronted to an adult-onset hypogammaglobulinemia. PMID- 21036647 TI - Correlations among clinical, radiographic, and sonographic scores for enthesitis in ankylosing spondylitis. AB - OBJECTIVES: To look for correlations among clinical, radiographic, and sonographic scores for enthesitis in patients with ankylosing spondylitis (AS). METHODS: Prospective study of 60 patients meeting modified New York criteria for AS. The clinical evaluation relied on the BASDAI, BASFI, and ASQoL and on a visual analog scale (VAS) for entheseal pain, as well as on two specific enthesitis indices, the Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) and the Spondyloarthritis Research Consortium of Canada Enthesitis Index (SPARCC). Radiographs and ultrasound scans were taken of five entheses on both sides (patellar insertion of the quadriceps tendon, proximal and distal insertions of the patellar tendon, and calcaneal insertions of the Achilles tendon and superficial plantar fascia). Ultrasound scans were obtained using a Philips HD 11TM machine with a high-frequency linear probe. RESULTS: We studied 48 men and 12 women with a mean age of 36+/-11 years. The radiographic score correlated with the VAS pain score, BASDAI, and BASFI. The sonographic score for acute enthesitis correlated only with the MASES, and the sonographic score for chronic enthesitis correlated with none of the clinical scores. The Doppler score correlated with the VAS pain score, BASDAI, BASFI, and ASQoL. The overall sonographic score correlated with the MASES and SPARCC. CONCLUSION: Good correlations were found between the clinical and sonographic scores for enthesitis. The radiographic score seemed correlated with the general AS parameters rather than with the clinical scores. Larger studies are needed to better define the role for radiographs and sonography of the entheses in the diagnosis of AS and follow-up of treated AS patients. PMID- 21036648 TI - Reactivation of cutaneous psoriasis during abatacept therapy for spondyloarthropathy. PMID- 21036649 TI - Adult-onset Still's disease with myocarditis successfully treated with the interleukin-1 receptor antagonist anakinra. PMID- 21036650 TI - [Deep bladder endometriosis: how do I...to perform a laparoscopic partial cystectomy?]. PMID- 21036652 TI - Sonochemical synthesis of a novel nano-rod two-dimensional zinc(II) coordination polymer; preparation of zinc(II) oxide nanoparticles by direct thermolyses. AB - A novel mixed-ligand zinc(II) coordination polymer, {[Zn(MU-4,4'-bipy)(MU-3 bpdh)(H(2)O)(2)](ClO(4))(2).(4,4'-bipy)(0.5)}(n) (1); 3-bpdh=2,5-bis(3-pyridyl) 3,4-diaza-2,4-hexadiene and 4,4'-bipy=4,4'-bipyridine, has been synthesized and characterized by IR, (1)HNMR and (13)CNMR spectroscopy. The single crystal X-ray data of compound 1 shows that this coordination polymer grows in two dimensions by two different bridging ligands, 4,4'-bipy and 3-bpdh. Also, nano-scale of compound 1 has been synthesized by sonochemical method and characterized by IR, X ray diffraction (XRD) and scanning electron microscopy (SEM). Thermal stability of compound 1 in single crystalline and nano-scale form was carried out by thermal gravimetric (TG) and differential thermal analysis (DTA). The ZnO nanoparticles were obtained by calcination of compound 1 at 500 degrees C under air atmosphere and by thermolyses in oleic acid at 200 degrees C. The zinc(II) oxide nanoparticles were characterized by X-ray diffraction (XRD) and scanning electron microscopy (SEM). PMID- 21036651 TI - Design and development of a multi-hole broadband-based ultrasonic transducer. AB - In order to improve the efficiency of ultrasonic energy transformed from electricity for an ultrasonic transducer array, a novel 1/2 wavelength multi-hole broadband-based transducer was designed, developed and evaluated. The low equivalent mass of the transducer is realized in this work through drilling holes on the output end of the horn. In comparison with a traditional transducer, the developed transducer has demonstrated a lower mechanical quality coefficient and a wider broadband. As a result, an ultrasound treatment system for crude oil has been developed based on the new transducer design. Furthermore, we have demonstrated the effectiveness of the ultrasound treatment system on viscosity reduction of crude oil and paraffin. PMID- 21036653 TI - Sono-assisted preparation of magnetic magnesium-aluminum layered double hydroxides and their application for removing fluoride. AB - A simple ultrasound-assisted co-precipitation method in combination with a calcination treatment was developed to prepare magnetic Mg-Al layered double hydroxides composite as an adsorbent material to remove fluoride ions from aqueous solutions. The application of ultrasound in the preparation process promoted the formation of the hydrotalcite-like phase and drastically shortened the time being required for preparation of the crystalline composite. It was found that the ultrasound irradiation assistance decreased the size of the composite particles and increased the specific surface area, being favorable to the improvement of the adsorption capacity. The composite prepared under the ultrasound irradiation exhibited fairly high maximum adsorption capacity of fluoride (47.7 mg g(-1)), which was 60% higher than that of the composite prepared without the ultrasound irradiation assistance with the same aging time. The thermodynamic and kinetic studies demonstrated that the adsorption of fluoride ions involved the reconstruction of the layered structure in the composite. In addition, the magnetic composite can be effectively and simply separated by using an external magnetic field, and then regenerated by desorption and calcination. PMID- 21036654 TI - Kinematics and flow characteristics of a magnetic actuated multi-cilia configuration. AB - The current paper continues the analysis of a completely novel method of fluid manipulation technology in micro-fluidics systems, inspired by nature, namely by the mechanisms found in ciliates. More information on this subject can be found at http://www.hitech-projects.com/euprojects/artic/. In order to simulate the drag forces acting on an array of artificial cilia, we have developed a computer code that is based on fundamental solutions of Stokes flow in a semi-infinite domain. The actuation mechanism consists of a bi-directional rotating excitation magnetic field. The magnetization induced by the magnetic field was calculated in a separate routine based on the Integral Nonlinear Equations Approach with 1D discretization of wire (cilium). Time averaged x-coordinate mass flow rates, streamlines and vorticity field are computed for several cilium configurations. The outcome and originality of this paper consist on assessing magnetic actuation as a practical tool for obtaining a consistent one-directional fluid flow. PMID- 21036655 TI - Evaluation of the generality and accuracy of a new mesh morphing procedure for the human femur. AB - Various papers described mesh morphing techniques for computational biomechanics, but none of them provided a quantitative assessment of generality, robustness, automation, and accuracy in predicting strains. This study aims to quantitatively evaluate the performance of a novel mesh-morphing algorithm. A mesh-morphing algorithm based on radial-basis functions and on manual selection of corresponding landmarks on template and target was developed. The periosteal geometries of 100 femurs were derived from a computed tomography scan database and used to test the algorithm generality in producing finite element (FE) morphed meshes. A published benchmark, consisting of eight femurs for which in vitro strain measurements and standard FE model strain prediction accuracy were available, was used to assess the accuracy of morphed FE models in predicting strains. Relevant parameters were identified to test the algorithm robustness to operative conditions. Time and effort needed were evaluated to define the algorithm degree of automation. Morphing was successful for 95% of the specimens, with mesh quality indicators comparable to those of standard FE meshes. Accuracy of the morphed meshes in predicting strains was good (R(2)>0.9, RMSE%<10%) and not statistically different from the standard meshes (p-value=0.1083). The algorithm was robust to inter- and intra-operator variability, target geometry refinement (p-value>0.05) and partially to the number of landmark used. Producing a morphed mesh starting from the triangularized geometry of the specimen requires on average 10 min. The proposed method is general, robust, automated, and accurate enough to be used in bone FE modelling from diagnostic data, and prospectively in applications such as statistical shape modelling. PMID- 21036656 TI - Chemically modified viruses: principles and applications. AB - The search for novel molecular materials has focused on viruses as natural nanomaterials. Historically studied for their effects as pathogens, recent advances have incorporated viruses as substrates for chemical modification, materials development, and therapeutic design. Here we will discuss recent advances in chemical strategies for modifying viruses, and the applications of these technologies. PMID- 21036657 TI - Chemical methods to detect S-nitrosation. AB - Nitric oxide (NO) is a cell-signaling molecule involved in a number of physiological and pathophysiological processes. Modification of cysteine residues by NO (or NO metabolites), that is S-nitrosation, changes the function of a broad spectrum of proteins. This reaction represents an important post-translational modification that transduces NO-dependent signals. However, the detection and quantification of S-nitrosation in biological samples remain a challenge mainly because of the lability of S-nitrosation products: S-nitrosothiols (SNO). In this review we summarize recent developments of the methods to detect S-nitrosation. Our focus is on the methods which can be used to directly conjugate the site(s) of S-nitrosation. PMID- 21036658 TI - Cell polarity and the control of apical growth in Streptomyces. AB - Streptomyces cells grow by building cell wall at one pole-the hyphal tip. Although analogous to hyphal growth in fungi, this is achieved in a prokaryote, without any of the well-known eukaryotic cell polarity proteins, and it is also unique among bacterial cases of cell polarity. Further, polar growth of Streptomyces and the related mycobacteria and corynebacteria is independent of the MreB cytoskeleton and involves a number of coiled-coil proteins, including the polarity determinant DivIVA. Recent progress sheds light on targeting of DivIVA to hyphal tips and highlight protein phosphorylation in the regulation of actinobacterial growth. Furthermore, cell polarity affects not only cell envelope biogenesis in Streptomyces, but apparently also assembly of fimbriae, conjugation and migration of nucleoids. PMID- 21036659 TI - The impact of medical record technologies on collaboration in emergency medicine. AB - PURPOSE: Electronic medical records (EMR) promise potential benefits for the practice of medical care. However, individual technologies such as EMR must interact with the work system as a whole - including people, technology and work practices - to enable or hinder the coordination of dynamic work demands. Based on this extended perspective, we address in this paper how support technologies (should) impact the coordination of work across multiple agents, controlling a dynamic domain with multiple, interacting processes. The technology we address is the medical record and the dynamic domain is emergency medicine as it is practiced in the U.S. METHOD: We performed 500 hours of naturalistic observations of physicians in two different hospital emergency departments in the Midwestern U.S differing in their reliance on paper or electronic medical records. RESULTS AND CONCLUSIONS: An analysis of work practice across the two hospitals revealed the role of medical records in facilitating or hindering the coordination of time sensitive and context dependent distributed work, as well as the specific influence of EMR. Recognizing that work practice compensates for the limitations of technology, we suggest four requirements for the design of EMR to promote workplace efficiency: facilitation of locally customized data presentations; support for integration of hitherto fragmented record systems and data formats; support for effective multi-user coordination of control tasks; and guidance for standardizing a level of detail in planning and documenting care. PMID- 21036660 TI - Ontology driven health information systems architectures enable pHealth for empowered patients. AB - The paradigm shift from organization-centered to managed care and on to personal health settings increases specialization and distribution of actors and services related to the health of patients or even citizens before becoming patients. As a consequence, extended communication and cooperation is required between all principals involved in health services such as persons, organizations, devices, systems, applications, and components. Personal health (pHealth) environments range over many disciplines, where domain experts present their knowledge by using domain-specific terminologies and ontologies. Therefore, the mapping of domain ontologies is inevitable for ensuring interoperability. The paper introduces the care paradigms and the related requirements as well as an architectural approach for meeting the business objectives. Furthermore, it discusses some theoretical challenges and practical examples of ontologies, concept and knowledge representations, starting general and then focusing on security and privacy related services. The requirements and solutions for empowering the patient or the citizen before becoming a patient are especially emphasized. PMID- 21036661 TI - The effect of multiple sclerosis and gender on central and peripheral fatigue during 2-min MVC. AB - OBJECTIVE: The aim of this study was to evaluate the effect of secondary progressive MS disease on central and peripheral fatigue in women and men during continuous 2-min maximal voluntary contractions (MVC) of the quadriceps muscle. METHODS: We studied age-matched (40-50-years of age) healthy individuals (men, n=9; women, n=10) and MS patients (men, n=9; women, n=9). The inclusion criteria for MS patients were a Kurtzke Expanded Disability Status Score <4 and a Fatigue Severity Scale Score >5. RESULTS: The electrically-induced torque, MVC, and voluntary activation (VA) values were significantly greater in healthy persons than in MS patients. At the end of exercise, the fatigue index of MVC and VA was greater in MS patients than in the healthy cohort, whereas the electrically induced torque was significantly decreased in healthy individuals. Peripheral fatigue was directly correlated with VA in MS patients; in contrast, it was inversely correlated with VA in healthy men. The variability of torque increased significantly during exercise and did not depend on MS and gender. CONCLUSIONS: MS increased central fatigue and diminished peripheral fatigue significantly during 2-min MVC; however, only peripheral fatigue was significantly greater in healthy men than in healthy women. SIGNIFICANCE: These results suggest the specified pattern of central and peripheral fatigue in MS patients and could be further exploited for potential therapeutic uses, for instance, to model exercise induced less central fatigue, and this may not be differentiated between men and women. PMID- 21036662 TI - Fluorescent quantitation method for differentiating the nativity of green fluorescent protein. AB - A gel imaging method was employed to quantitate the GFP that had been subjected to denaturation and degradation treatments. This method is able to differentiate the nativity of GFP by relating the observed changes in the position of fluorescent bands which is unable to be detected using the spectrofluorometric method. PMID- 21036665 TI - Cardiac follow-up for Indigenous children in Queensland. PMID- 21036664 TI - More membranes, more proteins: complex protein import mechanisms into secondary plastids. AB - Plastids are found across the tree of life in a tremendous diversity of life forms. Surprisingly they are not limited to photosynthetic organisms but also found in numerous predators and parasites. An important reason for the pervasiveness of plastids has been their ability to move laterally and to jump from one branch of the tree of life to the next through secondary endosymbiosis. Eukaryotic algae have entered endosymbiotic relationships with other eukaryotes on multiple independent occasions. The descendants of these endosymbiotic events now carry complex plastids, organelles that are bound by three or even four membranes. As in all endosymbiotic organelles most of the symbiont's genes have been transferred to the host and their protein products have to be imported into the organelle. As four membranes might suggest, this is a complex process. The emerging mechanisms display a series of translocons that mirror the divergent ancestry of the membranes they cross. This review is written from the viewpoint of a parasite biologist and seeks to provide a brief overview of plastid evolution in particular for readers not already familiar with plant and algal biology and then focuses on recent molecular discoveries using genetically tractable Apicomplexa and diatoms. PMID- 21036666 TI - Chlorhexidine impregnated central venous catheter inducing an anaphylatic shock in the intensive care unit. AB - Chlorhexidine, a bisbiguanide, is widely used as an antiseptic agent in medical practice as it has the greatest residual antimicrobial activity. Central venous catheters coated extraluminally with chlorhexidine have been made to reduce extraluminal contamination. By using both the chlorhexidine-alchohol skin preparation and antimicrobial-coated catheters during vascular cannulation, it can reduce catheter related bloodstream significantly [1]. The reduction in infection rate is especially vital in critically ill patients who require long term vascular access. Adverse reactions to chlorhexidine are rare and uncommon, and have been under-recognised as a cause of anaphylaxis. There are several reports of allergic reactions following exposure to chlorhexidine. We report of a case of anaphylaxis shock requiring cardiopulmonary resuscitation during the placement of a chlorhexidine impregnated central venous catheters. PMID- 21036667 TI - A single dose of Pegfilgrastim versus daily Filgrastim to evaluate the mobilization and the engraftment of autologous peripheral hematopoietic progenitors in malignant lymphoma patients candidate for high-dose chemotherapy. AB - Pegfilgrastim has equivalent efficacy to daily G-CSF in enhancing neutrophil recovery after chemotherapy, but conclusive data concerning its use for peripheral blood stem cell (PBSC) mobilization are lacking. From 2003 to 2008 we used high-dose chemotherapy in 64 lymphoma patients. At mobilization chemotherapy (ESHAP) the first 26 patients used unconjugated G-CSF, while the remaining 38 patients received Pegfilgrastim. At the time of harvest 25 patients collected stem cells after the use of G-CSF and 36 in the Peg group. No statistical by significant differences were observed in median peripheral CD34+ cells mobilized (77 MUL versus 71 MUL) and in collected PBSC (12.3 * 10(6)/kg versus 9.4 * 10(6)/kg p = 0.76). In the PEG group all patients collected the target PBSC with a single apheresis with a greater proportion of "optimal" mobilizers (83% versus 64%; p = 0.05). In conclusion a single dose of Pegfilgrastim could be a valid alternative to unconjugated G-CSF to mobilize PBSC in lymphoma patients. PMID- 21036663 TI - Intermediary metabolism in protists: a sequence-based view of facultative anaerobic metabolism in evolutionarily diverse eukaryotes. AB - Protists account for the bulk of eukaryotic diversity. Through studies of gene and especially genome sequences the molecular basis for this diversity can be determined. Evident from genome sequencing are examples of versatile metabolism that go far beyond the canonical pathways described for eukaryotes in textbooks. In the last 2-3 years, genome sequencing and transcript profiling has unveiled several examples of heterotrophic and phototrophic protists that are unexpectedly well-equipped for ATP production using a facultative anaerobic metabolism, including some protists that can (Chlamydomonas reinhardtii) or are predicted (Naegleria gruberi, Acanthamoeba castellanii, Amoebidium parasiticum) to produce H(2) in their metabolism. It is possible that some enzymes of anaerobic metabolism were acquired and distributed among eukaryotes by lateral transfer, but it is also likely that the common ancestor of eukaryotes already had far more metabolic versatility than was widely thought a few years ago. The discussion of core energy metabolism in unicellular eukaryotes is the subject of this review. Since genomic sequencing has so far only touched the surface of protist diversity, it is anticipated that sequences of additional protists may reveal an even wider range of metabolic capabilities, while simultaneously enriching our understanding of the early evolution of eukaryotes. PMID- 21036668 TI - Investigating the effect of a platelet additive solution on apheresis platelet and fibrin network ultrastructure. AB - In thrombotic events and diseases such as cancer, HIV/AIDS, dysfibrinogenaemia, as well as acute incidents (e.g. burn wounds), ultrastructure of platelets and fibrin networks change. In the current study, we compare the ultrastructure of platelets and fibrin networks of apheresis platelets stored in citrated human plasma (CP) and in a first-generation platelet additive solution (PAS) (T-Sol), to that of fresh donor plasma (FP). Eighteen apheresis platelet donors donated platelets on Trima(r)-AccelTM V5.2 and V5.1 cell separators. Six collections were stored for five days in autologous citrated plasma (CP); six collections were stored in 40% citrated human plasma and 60% PAS solution (CP/PAS) controlled, for the duration of storage, at a constant temperature (22+/-2 degrees C) with continuous flat-bed agitation; and six collections were stored in conditions uncontrolled for temperature and without continuous agitation. On days 1, 3 and 5, equal volumes of human thrombin were mixed with platelets collected in either CP or CP/PAS to form a coagulum (fibrin network containing platelet aggregates), followed by preparation for scanning electron microscopy. Results were compared with platelets and fibrin networks in FP. Typically, in FP, platelet aggregates with smooth membranes and pseudopodia are seen and fibrin networks arrange to form major, thick fibers and scattered, minor, thin fibers. On day 1, in CP and in all CP/PAS units, platelet ultrastructure compared well to that of FP, although the fibrin fibers were denser, with the minor fibers forming a matted layer over the major fibers. On day 3, in platelet units uncontrolled for temperature and without continuous agitation during storage, some platelet aggregates in CP/PAS showed typical apoptotic morphology, with shrinkage and membrane damage, but comparable fibrin networks were present. On day 5 however, in those units where storage conditions were uncontrolled and where the pH had decreased to below 6.4, no platelet aggregates were seen and fibrin was arranged into short, lumpy masses with no separate major or minor fibrin fibers visible. In those units stored at 22 degrees C with continuous flat-bed agitation, where pH was maintained >7.0, ultrastructure of platelets and fibrin network in CP/PAS was typical and similar to FP and CP at the end of five days of storage. Examining platelet and fibrin network ultrastructure may be useful, in addition to conventional laboratory analysis, in assessing the viability and potential clinical efficacy of platelets for transfusion and could play a role in the evaluation of new generation platelet additive solutions. PMID- 21036669 TI - In silico analysis of cis-acting regulatory elements in 5' regulatory regions of sucrose transporter gene families in rice (Oryza sativa Japonica) and Arabidopsis thaliana. AB - The regulation of gene expression involves a multifarious regulatory system. Each gene contains a unique combination of cis-acting regulatory sequence elements in the 5' regulatory region that determines its temporal and spatial expression. Cis acting regulatory elements are essential transcriptional gene regulatory units; they control many biological processes and stress responses. Thus a full understanding of the transcriptional gene regulation system will depend on successful functional analyses of cis-acting elements. Cis-acting regulatory elements present within the 5' regulatory region of the sucrose transporter gene families in rice (Oryza sativa Japonica cultivar-group) and Arabidopsis thaliana, were identified using a bioinformatics approach. The possible cis-acting regulatory elements were predicted by scanning 1.5kbp of 5' regulatory regions of the sucrose transporter genes translational start sites, using Plant CARE, PLACE and Genomatix Matinspector professional databases. Several cis-acting regulatory elements that are associated with plant development, plant hormonal regulation and stress response were identified, and were present in varying frequencies within the 1.5kbp of 5' regulatory region, among which are; A-box, RY, CAT, Pyrimidine-box, Sucrose-box, ABRE, ARF, ERE, GARE, Me-JA, ARE, DRE, GA-motif, GATA, GT-1, MYC, MYB, W-box, and I-box. This result reveals the probable cis acting regulatory elements that possibly are involved in the expression and regulation of sucrose transporter gene families in rice and Arabidopsis thaliana during cellular development or environmental stress conditions. PMID- 21036670 TI - Identification of essential food skills for skill-based healthful eating programs in secondary schools. AB - OBJECTIVE: To identify the food skills deemed essential to include in skill-based healthful eating programs in secondary schools. METHODS: Fifty-one food experts including home economics educators, chefs, nutritionists and dietitians, community educators, homemakers, and young people were recruited by invitation, mail, and advertising. Data were obtained by interviewing these food experts over 3 months. RESULTS: The identification of food skills forms the preliminary data for the first study of 3 in the design of programs in secondary schools. The data were reviewed for emerging themes and were coded by applying content analysis procedures. CONCLUSIONS AND IMPLICATIONS: Food skills required for young people were described under 4 themes as the areas of expertise required for young people to live independently. Understanding these skills would support teachers in designing programs that would address behavioral capabilities to improve young people's food preparation and eating behaviors. PMID- 21036671 TI - Takotsubo cardiomyopathy in a patient with previously undiagnosed hypertrophic cardiomyopathy with obstruction. AB - Takotsubo cardiomyopathy (TCM) is usually characterized by left ventricular anteroapical dysfunction in the absence of significant coronary disease commonly precipitated by an emotional or stressful trigger. Hypertrophic cardiomyopathy (HCM) is usually diagnosed on the basis of symptoms, family history, echocardiography, or by the presence of a characteristic murmur. We report a unique case of TCM occurring in a patient with previously undiagnosed HCM with left ventricular outflow tract (LVOT) obstruction who presented with an acute coronary syndrome and ultimately underwent successful alcohol septal ablation. The potential pathophysiologic correlations are discussed. PMID- 21036672 TI - Autonomic neuropathy is associated with impairment of dynamic cerebral autoregulation in type 1 diabetes. AB - HYPOTHESIS: The mechanisms underlying impairment of dynamic cerebral autoregulation in diabetes are not well known. Cardiovascular autonomic neuropathy (CAN) could contribute to dynamic cerebral autoregulation impairment. In this study, we assessed the association between CAN and impairment of dynamic cerebral autoregulation in patients with type 1 diabetes. METHODS: We evaluated dynamic cerebral autoregulation (DCA) in patients with type 1 diabetes and no history of cerebrovascular disease. DCA was assessed with transcranial Doppler using the correlation coefficient index Mx method. Mx was calculated from slow changes in mean cerebral blood flow velocity and mean arterial blood pressure. Increase in Mx indicates weaker DCA, with a threshold for impaired DCA above 0.3. Moderate CAN was defined as reduced heart rate variability (HRV) on the following tests: deep controlled breathing, Valsalva maneuver or initiation of active standing. Severe CAN was defined as reduced HRV associated with orthostatic hypotension. RESULTS: 60 patients were included (M/F: 33/27; mean age +/- SD: 46 years +/- 11.5). 23 patients had moderate CAN and 15 patients severe CAN. DCA was impaired in 37 patients. CAN was associated with impaired DCA (p = 0.005). Impairment of DCA was more pronounced in patients with severe CAN (p = 0.019). Glycosylated haemoglobin (HbA1c) was associated with impaired DCA in univariate analysis (p = 0.05). In multivariate analysis, only CAN was associated with impaired DCA (p = 0.007) whereas HbA1c was not (p = 0.161). CONCLUSIONS: CAN was associated with impaired DCA in type 1 diabetes. The magnitude of DCA impairment increased with the severity of CAN. PMID- 21036673 TI - The influence of heterochromatin on DNA double strand break repair: Getting the strong, silent type to relax. AB - DNA non-homologous end-joining (NHEJ) and homologous recombination (HR) represent the major DNA double strand break (DSB) pathways in mammalian cells, whilst ataxia telangiectasia mutated (ATM) lies at the core of the DSB signalling response. ATM signalling plays a major role in modifying chromatin structure in the vicinity of the DSB and increasing evidence suggests that this function influences the DSB rejoining process. DSBs have long been known to be repaired with two (or more) component kinetics. The majority (~85%) of DSBs are repaired with fast kinetics in a predominantly ATM-independent manner. In contrast, ~15% of radiation-induced DSBs are repaired with markedly slower kinetics via a process that requires ATM and those mediator proteins, such as MDC1 or 53BP1, that accumulate at ionising radiation induced foci (IRIF). DSBs repaired with slow kinetics predominantly localise to the periphery of genomic heterochromatin (HC). Indeed, there is mounting evidence that chromatin complexity and not damage complexity confers slow DSB repair kinetics. ATM's role in HC-DSB repair involves the direct phosphorylation of KAP-1, a key HC formation factor. KAP-1 phosphorylation (pKAP-1) arises in both a pan-nuclear and a focal manner after radiation and ATM-dependent pKAP-1 is essential for DSB repair within HC regions. Mediator proteins such as 53BP1, which are also essential for HC-DSB repair, are expendable for pan-nuclear pKAP-1 whilst being essential for pKAP-1 formation at IRIF. Data suggests that the essential function of the mediator proteins is to promote the retention of activated ATM at DSBs, concentrating the phosphorylation of KAP-1 at HC DSBs. DSBs arising in G2 phase are also repaired with fast and slow kinetics but, in contrast to G0/G1 where they all DSBs are repaired by NHEJ, the slow component of DSB repair in G2 phase represents an HR process involving the Artemis endonuclease. Results suggest that whilst NHEJ repairs the majority of DSBs in G2 phase, Artemis-dependent HR uniquely repairs HC DSBs. Collectively, these recent studies highlight not only how chromatin complexity influences the factors required for DSB repair but also the pathway choice. PMID- 21036676 TI - Commentary. PMID- 21036675 TI - Cystic fibrosis in Chilean patients: Analysis of 36 common CFTR gene mutations. AB - BACKGROUND: CFTR gene mutations have worldwide differences in prevalence and data on Chilean patients is scarce. METHODS: We studied 36 of the most common CFTR mutations in Chilean patients from the CF National Program [Programa Nacional de Fibrosis Quistica (PNFQ)] of the Ministry of Health of Chile. RESULTS: Two hundred and eighty-nine patients were studied. Fourteen different mutations were identified with an overall allele detection rate of 42.0%. Mutations with frequencies greater than 1% were p.F508del (30.3% of alleles), p.R334W (3.3%), p.G542X (2.4%), c.3849+10Kb C>T (1.7%), and p.R553X (1.2%). A north to south geographical gradient was observed in the overall rate of detection. CONCLUSIONS: Southern European CFTR mutations predominate in the Chilean population, but a high percentage of alleles remain unknown. Geographical heterogeneity could be explained in part by admixture. Complementary analyses are necessary to allow for effective genetic counselling and improve cost-effectiveness of screening and diagnostic tests. PMID- 21036674 TI - The ATR barrier to replication-born DNA damage. AB - Replication comes with a price. The molecular gymnastics that occur on DNA during its duplication frequently derive to a wide spectrum of abnormalities which are still far from understood. These are brought together under the unifying term "replicative stress" (RS) which likely stands for large and unprotected regions of single-stranded DNA (ssDNA). In addition to RS, recombinogenic stretches of ssDNA are also formed at resected DNA double strand breaks (DSBs). Both situations converge on a ssDNA intermediate, which is the triggering signal for a damage situation. The cellular response in both cases is coordinated by a phosphorylation-based signaling cascade that starts with the activation of the ATR (ATM and Rad3-related) kinase. Given that ATR is essential for replicating cells, understanding the consequences of a defective ATR response for a mammalian organism has been limited until recent years. We here discuss on the topic and review the findings that connect ATR to ageing and cancer. PMID- 21036677 TI - Electrochemical characterization of repaglinide and its determination in human plasma using liquid chromatography with dual-channel coulometric detection. AB - A simple, fast and sensitive HPLC method employing dual-channel coulometric detection for the determination of repaglinide in human plasma is presented. The assay involved extraction of repaglinide by ethyl acetate and isocratic reversed phase liquid chromatography with dual-channel coulometric detection. The mobile phase composition was 50mM disodium hydrogen phosphate/acetonitrile (60:40, v/v), pH of the mobile phase 7.5 set up with phosphoric acid. For all analyses, the first cell working potential was +380mV, the second was +750mV (vs. Pd/H(2)). Calibration curve was linear over the concentration range of 5-500nmolL(-1). Rosiglitazone was used as an internal standard. The limit of detection (LOD) was established at 2.8nmolL(-1), and the lower limit of quantification (LLOQ) at 8.5nmolL(-1). The developed method was applied to human plasma samples spiked with repaglinide at therapeutical concentrations. It was confirmed that the method is suitable for pharmacokinetic studies or therapeutic monitoring. PMID- 21036678 TI - Validated hydrophilic interaction LC-MS/MS method for determination of N-methyl-2 pyrrolidinone residue: Applied to a depletion study of N-methyl-2-pyrrolidinone in swine liver following intramuscular administration of drug N-methyl-2 pyrrolidinone formulation. AB - A hydrophilic interaction high-performance liquid chromatography coupled with tandem mass spectrometry method for determination of N-methyl-2-pyrrolidinone in swine liver was developed and validated. After the fortification of N-methyl-d(3) 2-pyrrolidinone-d(6) as the deuterium-labeled internal standard, N-methyl-2 pyrrolidinone in swine liver was extracted by acetonitrile and the supernatant was led through a C18+WAX mixed-mode SPE cartridge for removal of the matrix interferences. The final eluate was acidified by formic acid and then injected onto a 3MUm 15cm*2.1mm TX column for hydrophilic interaction chromatographic analysis. Mass spectrometry detection was carried on a PE Sciex API 4000 triple quadrupole mass spectrometer using positive turbo-ion spray ionization mode. The MRM transitions were 100->58 for N-methyl-2-pyrrolidinone and 109->62 for N methyl-d(3)-2-pyrrolidinone-d(6). Solvent calibration standards could be readily used for quantitative analysis of N-methyl-2-pyrrolidinone with excellent precision and accuracy, although there are endogenous levels of N-methyl-2 pyrrolidinone in many blank matrices. The true recovery was nearly 100% and the MRM signal of N-methyl-2-pyrrolidinone was suppressed about 30% because of the matrix effect. Nevertheless, N-methyl-d(3)-2-pyrrolidinone-d(6) completely compensated the ion-suppression effect and the injection-to-injection variation. The detection limit was 5ngg(-1) swine liver. The validated method was applied to a depletion study of N-methyl-2-pyrrolidinone in swine liver following intramuscular administration of a drug N-methyl-2-pyrrolidinone formulation. PMID- 21036679 TI - A highly sensitive ultra performance liquid chromatography-tandem mass spectrometric (UPLC-MS/MS) technique for quantitation of protein free and bound efavirenz (EFV) in human seminal and blood plasma. AB - A combined UPLC-tandem mass spectrometric (UPLC-MS/MS) technique has been validated for quantitation of protein free efavirenz (EFV) as well as total concentrations of EFV in human blood and seminal plasma. The analytical method possesses capabilities for concentration measurements of EFV ranging from 0.5 to 10,000ng/ml with an accuracy (%dev) of -5.2-8.0% and precision (%CV) of <8%. Standard curves were linear with coefficients of variation (r(2)) >0.98. The method employs a racemic fluorinated analog of EFV (F-EFV) as the internal standard. EFV and F-EFV were eluted from a reverse-phase UPLC column via gradient elution with detection via negative ion multiple reaction monitoring (MRM). EFV and F-EFV, respectively, were detected via the following MRM transitions: m/z 314.0>244.1 and m/z 298.0>227.9. The time required for the analysis of each sample was 8.0min. The analytical technique is capable of a reliable detection limit of ~15-20fmol of EFV injected on column. PMID- 21036681 TI - A peculiar cause of small-bowel intussusception and iron deficiency anaemia. PMID- 21036680 TI - Tissue proteomics of the human mammary gland: towards an abridged definition of the molecular phenotypes underlying epithelial normalcy. AB - Our limited understanding of the biological impact of the whole spectrum of early breast lesions together with a lack of accurate molecular-based risk criteria for the diagnosis and assignment of prognostic significance to biopsy findings presents an important problem in the clinical management of patients harboring precancerous breast lesions. As a result, there is a need to identify biomarkers that can better determine the outcome of early breast lesions by identifying subpopulations of cells in breast premalignant disease that are at high-risk of progression to invasive disease. A first step towards achieving this goal will be to define the molecular phenotypes of the various cell types and precursors - generated by the stem cell hierarchy - that are present in normal and benign conditions of the breast. To date there have been very few systematic proteomic studies aimed at characterizing the phenotypes of the different cell subpopulations present in normal human mammary tissue, partly due to the formidable heterogeneity of mammary tissue, but also due to limitations of the current proteomic technologies. Work in our laboratories has attempted to address in a systematic fashion some of these limitations and here we present our efforts to search for biomarkers using normal fresh tissue from non-neoplastic breast samples. From the data generated by the 2D gel-based proteomic profiling we were able to compile a protein database of normal human breast epithelial tissue that was used to support the biomarker discovery program. We review and present new data on the putative cell-progenitor marker cytokeratin 15 (CK15), and describe a novel marker, dihydropyriminidase-related protein 3 (DRP3) that in combination with CK15 and other well known proteins were used to define molecular phenotypes of normal human breast epithelial cells and their progenitors in resting acini, lactating alveoli, and large collecting ducts of the nipple. Preliminary results are also presented concerning DRP3 positive usual ductal hyperplasias (UDHs) and on single cell layer columnar cells (CCCs). At least two bona fide biomarkers of undifferentiated ERalpha/PgR negative luminal cells emerged from these studies, CK15 and c-KIT, which in combination with transformation markers may lead to the establishment of a protein signature able to identify breast precancerous at risk of progressing to invasive disease. PMID- 21036682 TI - Modified Fogli temporal lift. PMID- 21036683 TI - Aortic dissection associated with an obstructive aortic chondrosarcoma in a dog. AB - A 6-year-old, 35-kg, female spayed German wirehaired pointer was referred for evaluation of collapse/seizure-like activity and a suspected mediastinal mass. Echocardiographic examination revealed an obstructive, intraluminal aortic mass with aortic dissection. Gross and histopathological findings confirmed the aortic dissection with right pulmonary artery compression and an aortopulmonary fistula. The mass was histologically consistent with an intraluminal chondrosarcoma. To the authors knowledge this case represents only the second case of aortic chondrosarcoma in a dog, and interestingly the first case in either a dog or human to have aortic dissection associated with aortic obstruction by an intraluminal aortic tumor. PMID- 21036684 TI - Study of 25 X-chromosome SNPs in the Portuguese. AB - The importance of X-chromosome markers in individual identifications, population genetics, forensics and kinship testing is getting wide recognition. In this work, we studied the distributions of 25 X-chromosome single nucleotide polymorphisms (X-SNPs) in population samples from Northern, Central and Southern Portugal (n=305). The data were also compared with previous data from the Mediterranean area confirming a general genetic homogeneity among populations in the region. The X-SNP distribution in the three Portuguese regional samples did not show any significant substructure and the X-SNP distributions did not differ significantly from those of the majority of Mediterranean populations. PMID- 21036685 TI - Micro-geographic distribution of Y-chromosomal variation in the central-western European region Brabant. AB - One of the future issues in the forensic application of the haploid Y-chromosome (Y-chr) is surveying the distribution of the Y-chr variation on a micro geographical scale. Studies on such a scale require observing Y-chr variation on a high resolution, high sampling efforts and reliable genealogical data of all DNA-donors. In the current study we optimised this framework by surveying the micro-geographical distribution of the Y-chr variation in the central-western European region named Brabant. The Duchy of Brabant was a historical region in the Low Countries containing three contemporary Belgian provinces and one Dutch province (Noord-Brabant). 477 males from five a priori defined regions within Brabant were selected based on their genealogical ancestry (known pedigree at least before 1800). The Y-haplotypes were determined based on 37 Y-STR loci and the finest possible level of substructuring was defined according to the latest published Y-chr phylogenetic tree. In total, eight Y-haplogroups and 32 different subhaplogroups were observed, whereby 70% of all participants belonged to only four subhaplogroups: R1b1b2a1 (R-U106), R1b1b2a2* (R-P312*), R1b1b2a2g (R-U152) and I1* (I-M253*). Significant micro-geographical differentiation within Brabant was detected between the Dutch (Noord-Brabant) vs. the Flemish regions based on the differences in (sub)haplogroup frequencies but not based on Y-STR variation within the main subhaplogroups. A clear gradient was found with higher frequencies of R1b1b2 (R-M269) chromosomes in the northern vs. southern regions, mainly related to a trend in the frequency of R1b1b2a1 (R-U106). PMID- 21036686 TI - Imaging data in a prospective series of adult hip pain in under-50 year-olds. AB - Two hundred and ninety-two patients under the age of 50 years, presenting with mechanical hip pain, were included in a prospective multicenter study. In 241 cases, imaging assessment included AP standing pelvic X-ray and Lequesne's false profile (LFP) and/or lateral neck (Ducroquet, Dunn or variant) hip X-ray. Cross sectional arthroscan and/or arthro-MRI images were available in 81 cases. Exploration looked for acetabular and femoral head/neck dysplasia liable to induce cam or pincer anterior femoroacetabular impingement (AFAI), respectively. Labral and chondral lesions arise secondarily to hip osteoarthritis (HOA) and/or AFAI. Two-thirds of patients showed HOA. Only 6% showed a strictly normal aspect on imaging. More than half (52%) of cases had cam AFAI, half of these involving an osteophytic neck, associated in more than 90% of cases with large multifocal bone spurs of the head, neck and acetabula. These cases were considered ambiguous, due to the uncertainty as to the congenital nature of the cervico cephalic dysmorphy; if they are excluded, only 23% of the series involved cam AFAI. Crossover sign on AP standing pelvic X-ray is the best assessment criterion for acetabular retroversion, the most frequent form of acetabular dysplasia underlying pincer AFAI, and should be explored for. Secondary neck lesions were visible only on lateral neck view in 42% of cases: this view should be included in standard radiologic work-up in under-50 year-olds. The alpha angle can be measured on this type of lateral view and on axial arthroscan and arthro-MR images; more than half of the cases in which it was pathological involved an osteophytic neck and thus a pseudo-cam effect. PMID- 21036687 TI - Influence of cyclic bending loading on in vivo skeletal tissue regeneration from periosteal origin. AB - INTRODUCTION: Periosteum osteogenic and chondrogenic properties stimulate the proliferation then differentiation of mesenchymal precursor cells originating from its deeper layers and from neighboring host tissues. The local mechanical environment plays a role in regulating this differentiation of cells into lineages involved in the skeletal regeneration process. HYPOTHESIS: The aim of this experimental animal study is to explore the influence of cyclic high amplitude bending-loading on skeletal tissue regeneration. The hypothesis is that this mechanical loading modality can orient the skeletogenesis process towards the development of anatomical and histological articular structures. MATERIAL AND METHODS: A vascularised periosteal flap was transferred in close proximity to each knee joint line in 17 rabbits. On one side, the tibiofemoral joint space was bridged and loading occurred when the animal bent its knee during spontaneous locomotion. On the other side, the flap was placed 12 mm distal to the joint line producing no loading during bending. Tissue regeneration was chronologically analyzed on histologic samples taken from the 4th day to the 6th month. RESULTS: The structure and mechanical behavior of regenerating tissue evolved over time. As a result of the cyclic bending-loading regimen, cartilage tissue was maintained in specific areas of the regenerating tissue. When loading was discontinued, final osteogenic and fibrogenic differentiation occurred in the neoformed cartilage. Fissures developed in the cartilage aggregates resulting in pseudo-gaps suggesting similar processes to embryonic articular development. Ongoing mesenchymal stem cells stimulation was identified in the host tissues contiguous to the periosteal transfer. DISCUSSION: These results suggest that the pseudarthrosis concept should be reconsidered within the context of motion induced articular histogenesis. PMID- 21036688 TI - Hip arthroscopy technique and complications. AB - Hip arthroscopy is not a new technique but the seemingly limited indications and technical challenges involved have discouraged many since Burman documented his initial experiences (Burman, 1991). The current renaissance is largely driven by the expanding indications particularly in the management of femoroacetabular impingement. The figures from our own unit illustrate this well with 40% of hip arthroscopies in 1990 being purely diagnostic as compared with less than 5% at the present time. The focus of this chapter is the technical aspects of hip arthroscopy and the potential complications that can occur. PMID- 21036689 TI - The Internet and the therapeutic education of patients: A systematic review of the literature. AB - OBJECTIVES: To evaluate from a review of the literature the interest of using the Internet as a tool for the therapeutic education of patients. METHOD: A systematic review of Pubmed was carried out using the key words: the Internet, or World Wide Web and patient education, or patient preference, or self-care. The search was restricted to articles in English published between 1990 and 2009. References to the selected articles were also analyzed. Only randomized controlled studies were retained. RESULTS: Thirty-nine articles concerning 20 different diseases met the inclusion criteria and were analyzed. Different types of programs were proposed: informative, interactive, cognitive-behavioral and programs concerning self-management of the disease and the treatment. These different approaches were sometimes compared. The use of quality Internet sites made it possible to induce beneficial changes in lifestyle habits, and to diminish subjective and/or objective symptom severity in chronic invalidating diseases when used as a complement to traditional management. By using the Internet, patients were also able to improve decision-making skills to a degree that was at least as good as that obtained using traditional paper documents. CONCLUSION: The Internet is an effective complementary tool that can contribute to improving therapeutic education. Nonetheless, healthcare professionals should work with patients to create quality sites that correspond more closely to their expectations. It is also essential for learned societies such as the SOFMER to invest in therapeutic education on the Internet to make quality therapeutic education modules based on factual medical data and complying with good practices available on line. PMID- 21036690 TI - Distributions of major sub-types of lymphoid malignancies among adults in Mashhad, Iran. AB - BACKGROUND: Global variations in the frequency of the major sub-types of lymphoma have been reported. However, studies on different sub-types of adult malignant lymphoma had never been conducted in Mashhad, Iran. In this paper, we aimed to identify the major sub-types of malignant lymphoma in our area and compare the distribution with other published studies. METHODS: During a retrospective study we evaluate 391 adult patients with lymphoid malignancy from "Omid Hospital" - a cancer research center and an outpatient hematologic clinic in Mashhad - were evaluated from 2000 to 2009. Patients were reclassified using the World Health Organization (WHO) classification. RESULTS: The frequency of non-Hodgkin lymphomas (NHL) was 92% (n=359) and Hodgkin lymphoma (HL) was 8% (n=32). The most frequent NHL sub-type using WHO classification was diffuse large B cell lymphoma (DLBCL) and the second most common NHL was chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). The most common sub-type of HL was mixed cellularity. In this study the frequency of primary extranodal NHL in our study was 11.5%, which slightly less common than other eastern countries. CONCLUSION: Our findings add to the body of knowledge concerning geographic variations in the descriptive epidemiology of the major lymphoma sub-types. Such observations are extremely important since they potentially point to underling etiological variations. PMID- 21036691 TI - Structural and functional analysis of SMAD4 gene promoter in malignant pancreatic and colorectal tissues: detection of two novel polymorphic nucleotide repeats. AB - BACKGROUND: The tumor suppressor gene SMAD4 (DPC4) encodes for the common intracellular mediator of the TGF-beta superfamily pathway, which regulates numerous cellular processes, such as cell proliferation, cell differentiation, apoptosis, cell fate and migration. This study was aimed to investigate the presence of genetic variants in SMAD4 gene promoter in malignant pancreatic and colorectal tissue and to analyze their functional consequences. METHODS: The study was performed on genomic DNA isolated from malignant tissue samples obtained on surgery from 50 patients with pancreatic carcinoma and 50 patients with colorectal cancer. Screening for mutations within an 800bp-long fragment of the SMAD4 gene promoter was performed by DNA sequencing and two mononucleotide repeats, at positions -462 and -4, were found to be polymorphic in malignant tissue. The exact number of thymidines in the tracts -462T(15) and -4T(12) was determined by PCR with fluorescently labeled primers followed by capillary electrophoresis. Functional analysis of -462T(15)/-4T(12) haplotypes was performed by luciferase reporter assays. RESULTS: Haplotype -462T(14)/-4T(10) was found in 85% of pancreatic cancer tissues, but it was not present in any of colorectal cancer tissues. Statistically significant reduction (p<0.001) in activity was observed in the haplotype -462T(14)/-4T(10) in comparison with the haplotypes -462T(15)/-4T(12) and -462T(14)/-4T(11). CONCLUSION: Results of this study indicate that novel genetic variant -4T(10) in the SMAD4 gene promoter affects its activity and that element -4T(12) may play a role in transcriptional regulation of SMAD4 gene expression. Obtained results, though preliminary, also indicate that SMAD4 gene promoter haplotype -462T(14)/-4T(10) may represent a genetic marker of potential relevance for pancreatic and colorectal cancer. The findings of this study should be confirmed by further investigation in these two and other tumors, on larger number of patients and with different tumor stages. Translational research aimed at investigating potential application of mononucleotide repeats -462T(15) and -4T(12) in SMAD4 gene promoter as molecular markers in cancer may also prove useful. PMID- 21036692 TI - Ambient particulate matter air pollution and venous thromboembolism in the Women's Health Initiative Hormone Therapy trials. AB - BACKGROUND: The putative effects of postmenopausal hormone therapy on the association between particulate matter (PM) air pollution and venous thromboembolism (VTE) have not been assessed in a randomized trial of hormone therapy, despite its widespread use among postmenopausal women. OBJECTIVE: In this study, we examined whether hormone therapy modifies the association of PM with VTE risk. METHODS: Postmenopausal women 50-79 years of age (n = 26,450) who did not have a history of VTE and who were not taking anticoagulants were enrolled in the Women's Health Initiative Hormone Therapy trials at 40 geographically diverse U.S. clinical centers. The women were randomized to treatment with estrogen versus placebo (E trial) or to estrogen plus progestin versus placebo (E + P trial). We used age-stratified Cox proportional hazard models to examine the association between time to incident, centrally adjudicated VTE, and daily mean PM concentrations spatially interpolated at geocoded addresses of the participants and averaged over 1, 7, 30, and 365 days. RESULTS: During the follow-up period (mean, 7.7 years), 508 participants (2.0%) had VTEs at a rate of 2.6 events per 1,000 person-years. Unadjusted and covariate-adjusted VTE risk was not associated with concentrations of PM < 2.5 um (PM(2.5)) or < 10 um (PM(10))] in aerodynamic diameter and PM * active treatment interactions were not statistically significant (p > 0.05) regardless of PM averaging period, either before or after combining data from both trials [e.g., combined trial adjusted hazard ratios (95% confidence intervals) per 10 ug/m(3) increase in annual mean PM(2.5) and PM(10), were 0.93 (0.54-1.60) and 1.05 (0.72-1.53), respectively]. Findings were insensitive to alternative exposure metrics, outcome definitions, time scales, analytic methods, and censoring dates. CONCLUSIONS: In contrast to prior research, our findings provide little evidence of an association between short-term or long-term PM exposure and VTE, or clinically important modification by randomized exposure to exogenous estrogens among postmenopausal women. PMID- 21036695 TI - An evaluation of small-scale genetic diversity and the mating system in Zostera noltii on an intertidal sandflat in the Wadden Sea. AB - BACKGROUND AND AIMS: The dwarf eelgrass, Zostera noltii, is a predominant inhabitant of soft-bottom intertidal regions along the coasts of northern Europe. It is a monoecious, protogynous angiosperm in which the potential for self fertilization and inbreeding are high, especially if clone sizes exceed pollen dispersal distances. The aim of the present study was to determine the relationship between mating system and clonal structure, examine the relative roles of geitonogamous selfing and biparental inbreeding, measure pollen availability (multiple paternities) and estimate pollen dispersal. METHODS: A 100 m(2) plot was established in a large, intertidal Z. noltii meadow on the island of Sylt in the German Wadden Sea. A total of 256 adult shoots was sampled: one from the centre of 100 fixed 1-m(2) quadrats (large scale resolution) and an additional 156 from within eight randomly selected 1-m(2) sub-quadrats (small scale resolution). DNA was extracted from seeds and leaf tissue of all samples and genotyped with nine microsatellite loci. KEY RESULTS: Mating system analysis revealed high multilocus and single locus outcrossing rates. Average pollen dispersal distance was nearly the same as the average genet (clone) size. Multiple paternity was common and 20-30 % of mature seeds originated from matings within the plot. Among inbred seeds, most resulted from geitonogamy rather than biparental inbreeding. CONCLUSIONS: Moderate disturbances intrinsic to the intertidal habitat appear to facilitate seed recruitment by gap formation. Pollen dispersal distances are sufficient to maintain outcrossing and high clonal diversity. PMID- 21036694 TI - Association between simple sequence repeat-rich chromosome regions and intergenomic translocation breakpoints in natural populations of allopolyploid wild wheats. AB - BACKGROUND AND AIMS: Repetitive DNA sequences are thought to be involved in the formation of chromosomal rearrangements. The aim of this study was to analyse the distribution of microsatellite clusters in Aegilops biuncialis and Aegilops geniculata, and its relationship with the intergenomic translocations in these allotetraploid species, wild genetic resources for wheat improvement. METHODS: The chromosomal localization of (ACG)(n) and (GAA)(n) microsatellite sequences in Ae. biuncialis and Ae. geniculata and in their diploid progenitors Aegilops comosa and Aegilops umbellulata was investigated by sequential in situ hybridization with simple sequence repeat (SSR) probes and repeated DNA probes (pSc119.2, Afa family and pTa71) and by dual-colour genomic in situ hybridization (GISH). Thirty-two Ae. biuncialis and 19 Ae. geniculata accessions were screened by GISH for intergenomic translocations, which were further characterized by fluorescence in situ hybridization and GISH. KEY RESULTS: Single pericentromeric (ACG)(n) signals were localized on most U and on some M genome chromosomes, whereas strong pericentromeric and several intercalary and telomeric (GAA)(n) sites were observed on the Aegilops chromosomes. Three Ae. biuncialis accessions carried 7U(b)-7M(b) reciprocal translocations and one had a 7U(b)-1M(b) rearrangement, while two Ae. geniculata accessions carried 7U(g)-1M(g) or 5U(g) 5M(g) translocations. Conspicuous (ACG)(n) and/or (GAA)(n) clusters were located near the translocation breakpoints in eight of the ten translocated chromosomes analysed, SSR bands and breakpoints being statistically located at the same chromosomal site in six of them. CONCLUSIONS: Intergenomic translocation breakpoints are frequently mapped to SSR-rich chromosomal regions in the allopolyploid species examined, suggesting that microsatellite repeated DNA sequences might facilitate the formation of those chromosomal rearrangements. The (ACG)(n) and (GAA)(n) SSR motifs serve as additional chromosome markers for the karyotypic analysis of UM genome Aegilops species. PMID- 21036696 TI - Inhibition of Notch signaling reduces the stem-like population of breast cancer cells and prevents mammosphere formation. AB - BACKGROUND: Cancer stem cells (CSCs) are believed to be responsible for breast cancer formation and recurrence; therefore, therapeutic strategies targeting CSCs must be developed. One approach may be targeting signaling pathways, like Notch, that are involved in stem cell self-renewal and survival. MATERIALS AND METHODS: Breast cancer stem-like cells derived from cell lines and patient samples were examined for Notch expression and activation. The effect of Notch inhibition on sphere formation, proliferation, and colony formation was determined. RESULTS: Breast cancer stem-like cells consistently expressed elevated Notch activation compared with bulk tumor cells. Blockade of Notch signaling using pharmacologic and genomic approaches prevented sphere formation, proliferation, and/or colony formation in soft agar. Interestingly, a gamma-secretase inhibitor, MRK003, induced apoptosis in these cells. CONCLUSION: Our findings support a crucial role for Notch signaling in maintenance of breast cancer stem-like cells, and suggest Notch inhibition may have clinical benefits in targeting CSCs. PMID- 21036697 TI - Inhibition of BCL-2 in small cell lung cancer cell lines with oblimersen, an antisense BCL-2 oligodeoxynucleotide (ODN): in vitro and in vivo enhancement of radiation response. AB - BACKGROUND: Oblimersen, an ODN targeting BCL-2 RNA, has been shown to be effective in reducing BCL-2 expression in vitro and in in vivo models engineered to overexpress BCL-2. The present study evaluated the efficacy of combining BCL-2 ODN and radiation in small-cell lung cancers (SCLC) cell lines. MATERIALS AND METHODS: The in vitro effect was determined using short term (cell viability) and long term (clonogenic) assays. Apoptosis, BCL-2 expression and intratumoural uptake of the FAM-ODN with or without prior radiation treatment were also evaluated. Combination of ODN and RT was also assessed in vivo. RESULTS: Radiation was shown to increase intracellular and intratumoural penetration of oblimersen, confirming previous results obtained in prostate cancer xenograft models. Oblimersen decreased BCL-2 protein expression in vitro and in vivo. BCL-2 ODN sensitised H69 cells to radiation in vitro and in vivo. Oblimersen increased radiation-induced apoptosis and decreased in vivo tumoural vascularisation. CONCLUSION: Oblimersen was shown to increase in vitro and in vivo effect of RT on SCLC cell lines. Radiation increases intracellular and intratumoural penetration of ODN. This pre-clinical study argues in favour of clinical development in localised SCLC. PMID- 21036698 TI - 5-fluorouracil-induced death of Jurkat T-cells--a role for caspases and MCL-1. AB - 5-Fluorouracil (5-FU) is frequently used in cancer treatment. Previous studies with 5-FU suggest that proapoptotic protein BAX and tumor suppressor protein TP53 are central factors in this process. As the leukemic T cell line Jurkat E6 has mutations in both these genes, we investigated a possible activation of alternative death pathways following 5-FU treatment. Here we show that 5-FU triggers apoptosis in Jurkat cells in a dose-dependent manner. Death responses were only moderately attenuated in the presence of a general caspase inhibitor. However, flow cytometric analysis showed activation of caspase 3 and a slight increase in ROS generation in a time- and dose-dependent manner. Furthermore, we observed 5-FU induced PARP cleavage and notably, reduced expression of antiapoptotic MCL-1L associated with the appearance of proapoptotic MCL-1S. Our results demonstrate the activation of alternative death pathways following treatment with 5-FU, despite mutations in the TP53 and BAX genes. PMID- 21036699 TI - Poly-N-acetyl glucosamine gel matrix as a non-viral delivery vector for DNA-based vaccination. AB - Intramuscular administration of plasmid DNA vaccines is one of the main delivery approaches that can generate antigen specific T cell responses. However, major limitations of the intramuscular delivery strategy are the low level of myocyte transfection, resulting in a minimal level of protein expression; the inability to directly target antigen presenting cells, in particular dendritic cells, which are critical for establishment of efficacious antigen-specific immune responses. Although several viral vectors have been designed to improve plasmid DNA delivery, they have limitations, including the generation of neutralizing antibodies in addition to lacking the simplicity and versatility required for universal clinical application. We have developed an inexpensive non-viral delivery vector based on the polysaccharide polymer poly-N-acetyl glucosamine with the capability to target dendritic cells. This vector is fully biocompatible, biodegradable, and nontoxic. The advantage of the application of this delivery system relative to other approaches is discussed. PMID- 21036701 TI - E-cadherin accumulation within the lymphovascular embolus of inflammatory breast cancer is due to altered trafficking. AB - E-Cadherin functions as a tumor suppressor in some invasive breast carcinomas and metastasis is promoted when its expression is lost. It has been observed, however, that in one of the most aggressive human breast cancers, inflammatory breast cancer (IBC), E-cadherin is overexpressed and this accounts for the formation of the lymphovascular embolus, a structure efficient at metastasis and resistant to chemotherapy through unknown cytoprotective mechanisms. Studies using a human xenograft model of IBC, MARY-X, indicate that the mechanism of E cadherin overexpression is not transcriptional but related to altered protein trafficking. By real-time RT-PCR, E-cadherin transcript levels in MARY-X were 3- to 11-fold less than in other E-cadherin positive human breast carcinoma lines but the protein levels were 5- to 10-fold greater. In addition, several smaller E cadherin protein fragments, e.g. 95 kDa, were present. To explain these observations, it was hypothesized that there may be altered protein trafficking. A real-time RT-PCR screen of candidate molecules generally known to regulate protein trafficking was conducted. The screen revealed 3.5- to 7-fold increased ExoC5 level and 10 to 20 fold decreased HRS and RAB7 levels, which was confirmed in human microdissected lymphovascular emboli. Since these alterations may only be correlative with E-cadherin overexpression, one of the molecules, Rab7, was selectively knocked down in MCF-7 cells. An increase in the full length 120 kDa E cadherin and the de novo appearance of the 95 KD band were observed. These findings suggest that it is the altered E-cadherin trafficking that contributes to its oncogenic rather than suppressive role in IBC. PMID- 21036700 TI - Androgen receptor-mTOR crosstalk is regulated by testosterone availability: implication for prostate cancer cell survival. AB - BACKGROUND: Signaling between androgen receptor (AR) and mTOR may be crucial for prostate cancer cells to endure the low androgen and suboptimal nutrient conditions produced by androgen deprivation therapy. MATERIALS AND METHODS: AR and mTOR cross-talk was examined in LNCaP cells exposed to either high or low testosterone. AR and mTOR activities were modified separately using either siRNA knockdown or specific chemical inhibitor. The biological significance of the reciprocal communication was assessed by susceptibility to glucose deprivation induced cell death. RESULTS: AR positively regulated mTOR activity in both low and high testosterone levels. TSC1 and TSC2, the two negative regulators of mTOR, may be involved since both were up-regulated by AR knockdown. Sub-baseline mTOR increased AR protein levels. However, this effect only occurred with low testosterone. More cells underwent apoptosis if AR function was inhibited during glucose deprivation, which significantly depressed mTOR activity. CONCLUSION: The compensatory increase of AR function due to a repressed mTOR signal is advantageous for survival. Disrupting this loop at the time of initiation of androgen deprivation therapy may delay, or even prevent, the recurrence of prostate cancer. PMID- 21036702 TI - Synergistic effects of topoisomerase I inhibitor, SN38, on Fas-mediated apoptosis. AB - Inhibitors of topoisomerase I, such as camptothecin, have proven to be among the most promising new classes of anti-neoplastic agents introduced into the clinical setting in recent years. Irinotecan (CPT-11) is one of the most widely used camptothecin analogs and is converted to form the active metabolite SN-38. The present study was designed to explore apoptosis induced by SN38 and anti-Fas antibody (CH11) in WR/Fas-SMS1 cells and its possible mechanisms. The results demonstrate that combination of SN38 and CH11 synergistically enhanced cell apoptosis in WR/Fas-SMS1 cells. Western blotting analysis showed that combination of SN38 and CH11 activated the ATM-Chk1-p53 pathway, increased protein expression of phospho-p53 and cleavaged caspase-3, but down-regulated expression of phospho p21. Our data suggest that combination of SN38 and CH11 enhanced apoptosis through down-regulation of p21 phosphorylation. In conclusion, inhibition of p21 could be a new adjuvant approach in cancer therapy. PMID- 21036703 TI - Methylation-mediated silencing of TMS1 in pancreatic cancer and its potential contribution to chemosensitivity. AB - BACKGROUND: Resistance to chemotherapeutic agents, resulting in part from epigenetic silencing of pro-apoptotic genes, is one of the causes of treatment failure of pancreatic cancer. We examined whether epigenetic silencing of target of methylation induced silencing 1 (TMS1) contributes to resistance to chemotherapy in pancreatic cancer. MATERIALS AND METHODS: Methylation analysis was performed by methylation-specific PCR (MS-PCR) and gene expression was analyzed by quantitative reverse transcriptase PCR (qRT-PCR). MIA PaCa-2 cells were transfected with pCMV6-XL5/TMS1 plasmid and the effect of TMS1 expression on sensitivity to gemcitabine and docetaxel was determined. Cell viability was measured using Cell Titer Blue assay. RESULTS: TMS1 expression was repressed in MIA PaCa-2 cells by DNA methylation. Up-regulation of TMS1 by recombinant gene expression in MIA PaCa-2 cells or by pre-treatment of these cells with 5 azacytidine resulted in enhanced sensitivity to gemcitabine and docetaxel. CONCLUSION: Our results suggest that TMS1 is a potential therapeutic target in pancreatic cancer. PMID- 21036704 TI - Second-generation substituted quinolines as anticancer drugs for breast cancer. AB - Cancer cells have reduced capacity for gap junctional inter-cellular communication (GJIC). One feasible approach to reduce growth of cancer cells is to enhance GJIC. This report shows that a second-generation substituted quinoline, PQ7, has anti-tumor effect. Scrape load/dye transfer and colony growth assays were performed to measure GJIC and tumor formation of T47D breast cancer cells. PQ7 at 500 nM induced a 16-fold increase in the GJIC in T47D cells. In addition to an increase in GJIC, a 50% decrease of colony growth was observed with 100 nM of PQ7. PQ7-treated nu/nu mice showed a 100% regression of xenograft tumor growth of T47D cells. The results show that PQ7 has a promising role in exerting anti-tumor activity in human breast cancer cells. PMID- 21036706 TI - A positive relationship between filamin and VEGF in patients with lung cancer. AB - Induction of angiogenic responses by multiple factors, a crucial step in tumor growth and metastasis, is not completely understood. Recently, involvement of the cytoskeletal actin-binding proteins in angiogenesis has been suggested as a target for anti-neovascular cancer therapy in vitro. In this study, the expression of filamin A (FLNA) and vascular endothelial growth factor (VEGF) in paraffin-embedded tumor samples from patients with well-characterized lung tumors was immunohistochemically analyzed and compared with clinical variables and survival outcome. A positive expression of FLNA and VEGF was detected in the cytoplasm of tumor cells in 66 (48.2%) and 69 (50.4%) of the 137 patients with lung cancer, respectively (p<0.0001). A significant difference was observed between FLNA expression and VEGF expression. Although our findings do not suggest that the expression of FLNA alone plays an independent prognostic role, the angiogenesis pathway mediated by FLNA appears to be responsible for controlling the growth of lung tumors. PMID- 21036705 TI - Orthotopic fluorescent peritoneal carcinomatosis model of esophageal cancer. AB - AIM: Orthotopic models utilizing orthotopic implantation have been used for developing cancer models of multiple tumor entities. The aim of this study was to evaluate the role of orthotopic injection in establishing a model of esophageal cancer using a human green fluorescent protein (GFP) cell line of human esophageal carcinoma. MATERIALS AND METHODS: Nude mice were orthotopically injected in the abdominal esophagus with stably transfected GFP-PT1590 cells. Tumor progression was examined by fluorescence imaging. RESULTS: Fifty percent of animals developed extensive peritoneal spread without a distinct primary tumor at the injection site. Continuous and metastatic spread to the liver, lungs, and lymph nodes was also observed. Fluorescence imaging enabled fast and specific visualization of tumor progression without the need for anesthesia. Intraperitoneal and metastatic tumor spread of GFP-PT1590 esophageal carcinoma demonstrated a highly aggressive but heterogeneous behaviour. Although injection of the esophageal carcinoma cell line GFP-PT1590 did not lead to primary esophageal tumor development at the site of injection, 50% of the mice developed extensive peritoneal spread, as well as lymph node and organ metastasis. CONCLUSION: The orthotopic cell injection model resulted in peritoneal carcinomatosis of esophageal adenocarcinoma, which could be visualized in real time using fluorescence imaging. PMID- 21036707 TI - Effects of ILTG on DAPK1 promoter methylation in colon and leukemia cancer cell lines. AB - AIMS: The aim of this study was to describe quantitatively the potential demethylating effects of the plant-derived compound isoliquritigenin (ILTG) on the death-associated protein kinase-1 (DAPK1) promoter region of colon cancer and leukemia cell lines. METHODS: Methylation-specific real-time polymerase chain reaction-melting curve analysis (MSP-MCA) was the primary method used. A simple cytotoxicity assay and an ethidium bromide displacement assay were used to evaluate the chemopreventive indices and account for any problems in fluorometric assessment caused by intercalating potential of the compound of interest. RESULTS: ILTG was able to affect the melting curve significantly when using MSP MCA. ILTG exhibited a demethylating activity on HT-29 colon cancer and HL-60 leukemia cells. CONCLUSION: ILTG found in licorice (Glycyrrhiza glabra) may have the potential for being a cancer chemopreventive agent. From the specific assays performed in this experiment, ILTG appears to possess potential for development as a demethylating agent for either colon cancer or leukemia cancer prevention. PMID- 21036708 TI - Inhibition of GST-pi nuclear transfer increases mantle cell lymphoma sensitivity to cisplatin, cytarabine, gemcitabine, bortezomib and doxorubicin. AB - PURPOSE: Mantle cell lymphoma (MCL) is a chemoresistant lymphoma overexpressing the class pi glutathione-S-transferase (GST-pi). The nuclear localisation of GST pi is induced by chemotherapy and is correlated to cell resistance. In this study, the effect of the Agaricus bisporus lectin (ABL), a GST-pi nuclear transfer inhibitor, on the chemosensitivity of MCL cells was investigated. METHODS: The proliferation of three MCL cell lines was evaluated in the presence of doxorubicin (DOX), cisplatin (CDDP), cytarabine (Ara-C), gemcitabine (GEM) or bortezomib with or without ABL pre-treatment. RESULTS: The cytotoxic activities of CDDP, Ara-C, GEM and bortezomib were increased in all cell lines. The DOX cytotoxic activity was enhanced in two of three cell lines. The inhibition of GST pi nuclear transfer led to the potentialisation of all drug combinations. CONCLUSION: The inhibition of the nuclear transfer of GST-pi increases the MCL sensitivity to DOX, CDDP, Ara-C, GEM and bortezomib, alone or in combination. PMID- 21036709 TI - IL-1 receptor antagonist anakinra enhances tumour growth inhibition in mice receiving peptide vaccination and beta-(1-3),(1-6)-D-glucan. AB - BACKGROUND: Immunotherapy of cancer by vaccination is hampered by tumour-mediated immune suppression, to which pro-inflammatory cytokines such as interleukin-1 (IL 1) and IL-6 contribute. In mouse models, IL-1-receptor antagonist (IL-1 Ra) diminished inflammation and tumour growth when administered during or shortly after tumour inoculation. MATERIALS AND METHODS: The capacity of IL-1 Ra anakinra to reduce IL-1-induced production of IL-6 in order to improve the efficacy of a subsequent booster vaccination with survivin-derived peptides and soluble beta glucan as adjuvant was tested in colon-26 adenocarcinoma-bearing Balb/c-mice. RESULTS: Bolus administration of anakinra into non-immunized mice with macroscopic tumour significantly lowered serum levels of IL-6 without inhibiting tumour growth. When administered to pre-immunized mice bearing a palpable tumour, IL-1 Ra enhanced growth inhibition of a subsequent booster vaccination, although serum-IL-6 was not reduced and the number of IFN-gamma-producing splenic CD8(+) T cells was not increased. CONCLUSION: Anakinra contributes to growth-inhibition of small tumours, presumably by blocking IL-1 as tumour growth-promoting factor rather than by facilitating an enhanced CTL response. PMID- 21036710 TI - Salen-manganese complexes: sophisticated tools for the analysis of intercellular ROS signaling pathways. AB - Salen-manganese complexes, such as EUK-8 and EUK-134 are known as catalase mimetics with superoxide dismutase (SOD) and peroxidase mimetic activity. Here we show that the concentration-dependent use of salen-manganese complexes within the appropriate time window and with parallel control of signaling parameters allows complex interactions during intercellular induction of apoptosis to be studied. At very low concentrations, salen-manganese complexes can abrogate consumption reactions between HOCl and hydrogen peroxide, as well as NO and hydrogen peroxide, and thus the major signaling pathways are enhanced. At higher concentrations of the compounds, all major signaling pathways are inhibited, thereby the catalase mimetic activity of the compounds affects both hydrogen peroxide and peroxynitrite. The ratio between available hydrogen peroxide and salen-manganese complexes defines whether reactive oxygen species (ROS) effects are inhibited or apoptosis is induced by the compounds. The SOD mimetic activity of salen-manganese complexes seems to be insufficient to interfere with intercellular ROS signaling. PMID- 21036711 TI - Endocrine gland derived-VEGF is down-regulated in human pituitary adenoma. AB - BACKGROUND: Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) is an angiogenic molecule restricted to endocrine glands and, particularly, to steroid-secreting cells. The expression of EG-VEGF and its significance in human adenohypophysis in physiological and pathological conditions is still unknown. MATERIALS AND METHODS: In this study, we investigated by immunohistochemistry the expression of EG-VEGF in 2 samples of normal adenohypophysis and 43 bioptic samples of pituitary adenoma. Moreover, the expression of growth hormone (GH), prolactin (PRL), follicle-stimulating hormone (FSH), luteinizing hormone (LH), thyroid-stimulating hormone (TSH) and adrenocorticoprophic hormone (ACTH) were also estimated. RESULTS: The results of this study for the first time demonstrate a down-regulation of EG-VEGF expression in human pituitary adenoma as compared to normal adenohypophysis, suggesting an impaired function of the neoplastic cells in terms of hormone release in the blood stream, as a consequence of impaired tumor angiogenesis in the tumor. CONCLUSION: On the basis of our data showing a marked decrease in the expression of EG-VEGF in pituitary adenoma, with the exception of LH-secreting adenomas, we suggest that LH might be involved in the induction of EG-VEGF secretion. PMID- 21036712 TI - Evaluation of in vitro biological activity of O-alkylated hydroxamic derivatives of some nonsteroidal anti-inflammatory drugs. AB - AIM: Several published studies suggest that nonsteroidal anti-inflammatory drugs (NSAIDs) are promising anticancer agents. This study examined the in vitro effect of O-alkylated NSAID hydroxamic acid derivatives 3a-i on cell survival for a panel of human tumour cell lines, their cytotoxicity on normal human fibroblasts and their antiviral activity. MATERIALS AND METHODS: Established methods of cell viability testings, cell cycle analyses and Western blot assays were used. RESULTS: O-Alkylated NSAID hydroxamic acid derivatives exerted poor antiviral activity butreduced the viability of the studied tumour cell lines in a concentration-dependent manner showing low cytotoxic effect on normal fibroblasts. Compounds 3a and 3i were shown to be potent inhibitors of the growth of MIA PaCa-2 cell line. They induced p53-independent S-phase arrest and triggered caspase 3-dependent apoptosis. CONCLUSION: Two novel O-alkylated NSAID hydroxamic acid derivatives may be useful in the treatment of pancreatic cancer and should be further evaluated in vivo. PMID- 21036713 TI - PKCalpha/beta I inhibitor Go6976 induces dephosphorylation of constitutively hyperphosphorylated Rb and G1 arrest in T24 cells. AB - BACKGROUND: Rb functions as a key controller of the G(1)-S transition of the cell cycle, and its inactivation leads to a defective G(1) checkpoint. Bladder cancer frequently displays alterations in Rb such as constitutive hyperphosphorylation which results in inactive Rb and progression of cells to the S-phase. Several protein kinase C (PKC) inhibitors are currently undergoing clinical trials as anticancer drugs. MATERIALS AND METHODS: T24 urinary bladder carcinoma cells, known to express hyperphosphorylated Rb, were treated with PKCalpha/betaI inhibitor Go6976. The treated cells were subjected to cell cycle analysis, cell growth assay and Western blots for Rb and cdc2 phosphorylation. RESULTS: The treatment resulted in Rb dephosphorylation at Ser 795 and Ser 807/811, and cdc2 dephosphorylation at Tyr15. Subsequent G(0/1) arrest and reduced proliferation rates were observed. CONCLUSION: The results show that Go6976 can be used to restore constantly hyperphosphorylated and therefore constantly inactive Rb function in cancer cells. PMID- 21036714 TI - Staining with highly sensitive Coomassie brilliant blue SeePicoTM Stain after FlamingoTM fluorescent gel stain is useful for cancer proteomic analysis by means of two-dimensional gel electrophoresis. AB - Highly sensitive Coomassie brilliant blue SeePicoTM Stain was applied for proteomic analysis using two-dimensional gel electrophoresis (2-DE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). After staining with FlamingoTM Fluorescent Gel Stain, the images of the protein spots were analyzed, and 424 protein spots were detected. After washing with Milli-Q water three times, the gels were re-stained with SeePicoTM Stain and the images of the protein spots were analyzed; 272 spots were detected. To assess whether SeePicoTM Stain alters MS analysis, a spot was picked up and was analyzed by LC-MS/MS. The MS analysis showed good protein identification. These results show a possible role for SeePicoTM Stain in cancer proteomics using 2-DE and MS. PMID- 21036715 TI - Curcumin-altered p53-response genes regulate radiosensitivity in p53-mutant Ewing's sarcoma cells. AB - AIM: Curcumin has been demonstrated to have antitumor effects including radiosensitization by modulating many molecular targets including p53. Herein, we investigated the radiosensitizing effect of curcumin in p53 mutant Ewing's sarcoma (ES) cells. MATERIALS AND METHODS: Cells exposed to radiation with or without curcumin were examined for transcriptional and translational levels of p53 downstream targets and its influence in regulated apoptosis, DNA fragmentation, cell survival and clonal expansion. RESULTS: Curcumin significantly caused radiation induced expression of p21 and Bax, and reduced BclXl, Mcl1 with only marginal Bcl2 modulation. As a positive control to the study, both transcriptional and translational levels of p53 remained unchanged after radiation with/without curcumin. Conversely, curcumin caused radiation induced apoptosis and DNA fragmentation. Consistently, curcumin enhanced radiation-induced cytotoxicity and clonal expansion. CONCLUSION: These results suggest that curcumin potentially radiosensitizes p53-mutant ES cells by regulating IR-modulated p53-response genes. However, the curcumin-associated p53 independent regulation of downstream targets remains to be explored. PMID- 21036716 TI - Antiproliferative effects of rapamycin and celecoxib in angiosarcoma cell lines. AB - BACKGROUND/AIM: Beyond their primary field of application some well-established drugs exhibit antitumour effects in a variety of cancers. The aim of this study was to investigate the effects of the COX2 inhibitor celecoxib and the mTOR antagonist rapamycin on angiosarcoma cell lines. MATERIALS AND METHODS: Cell proliferation was measured in ASM, ISOS 1 and ISO HAS angiosarcoma cell lines with the BrdU assay. RESULTS: In all angiosarcoma cell lines, celecoxib as well as rapamycin inhibited cell growth in a dose-dependent manner. In ASM and ISOS 1, but not in ISO HAS angiosarcoma cells, additive growth inhibitory effects were detected by combining both agents. CONCLUSION: Our results indicate that angiosarcoma cell proliferation can be inhibited by subtoxic doses of rapamycin and celecoxib. Due to their direct and stroma-mediated anticancer activities, mTOR antagonists and COX2 inhibitors represent very promising drugs in the palliative treatment of angiosarcoma. PMID- 21036717 TI - Studies on combinations of platinum with paclitaxel and colchicine in ovarian cancer cell lines. AB - Ovarian cancer remains an ongoing challenge because of the occurrence of resistant forms of tumour for which the drugs fail to function. Combination therapy using drugs with different mechanisms of action offer a means of overcoming drug resistance and reducing the side-effects. In this study, binary combinations of four platinum compounds cisplatin (Cs), oxaliplatin (Ox), YH12 [trans-PtCl(2)(ammino) {imidazo-(1,2-alpha)pyridine}] and TH1 [{trans PtCl(NH(3))(2)}(2) {trans-Pt(3-hydroxypyridine)(2)(H(2)N(CH(2)) 6NH(2))(2)}Cl(4)] and two plant-based mitotic inhibitors paclitaxel (Tx) and colchicine (Co) have been used against ovarian cancer cell lines A2780 and A2780(cisR) using five different sequences of addition: 0/0 h, 4/0 h, 0/4 h, 24/0 h and 0/24 h. The strongest synergistic effect was observed when the plant compound (Tx or Co) was added first followed by platinum four hours later with combination index at 50% effect level (fa= 0.5) ranging from 0.03 to 0.36 and 0.10 to 0.72 in A2780 and A2780(cisR) cells respectively. Of all the platinum compounds, Cs showed the greatest synergism when combined with Tx and Co (combination index, CI(50)=0.03 in A2780 and from 0.10 to 0.12 in A2780(cisR)). With the sequence 24/0 h, platinum compounds showed greater synergistic effect with Co than Tx in A2780(cisR). With the sequences 0/4 h and 0/24 h, most of the combinations showed weak synergism to antagonism, especially in A2780(cisR). Antagonism was also observed when the two compounds were added simultaneously, especially in A2780(cisR). CONCLUSION: Binary combinations of platinum compounds Cs, Ox, YH12 and TH1 with plant compounds Tx and Co applied to ovarian cancer cell lines showed sequence- and concentration-dependent synergism. The results may have profound implications in therapy, if found to be true in vivo. PMID- 21036718 TI - Multimodality imaging and preclinical evaluation of 177Lu-AMBA for human prostate tumours in a murine model. AB - AMBA (DO3A-CH(2)CO-G-(4-aminobenzoyl)-QWAVGHLM-NH(2)) is a bombesin (BN)-like peptide having high affinity with gastrin-releasing peptide receptors (GRPr).(177)Lu-AMBA is currently undergoing clinical trial as a systemic radiotherapy for hormone refractory prostate cancer (HRPC) patients. This study evaluated the biodistribution, pharmacokinetics, bioluminescent imaging (BLI) and microSPECT/CT imaging of (177)Lu-AMBA in PC-3M-luc-C6 luciferase-expressing human prostate tumour-bearing mice. Plasma stability of (177)Lu-AMBA could be maintained up to 55.67+/-6.07% at 24 h in a protection buffer. High positive correlations of PC-3M luc-C6 tumour growth in SCID mice between caliper measurement and BLI were observed (R(2)=0.999). Both the biodistribution and microSPECT/CT imaging in PC-3M-luc-C6 bearing-tumour mice showed that (177)Lu AMBA in tumour uptake could be retained for 24 h. The distribution half-life (t(1/2alpha)) and the elimination half-life (t(1/2beta)) of (177) Lu-AMBA in mice were 0.52 h and 26.6 h, respectively. These results indicated that BLI could be used to monitor the growth of tumour. High uptake of (177)Lu-AMBA in PC-3M-luc-C6 tumour-bearing mice by microSPECT/CT imaging can further evaluate the potential of (177)Lu-AMBA therapy for PC-3M-luc-C6 tumours. PMID- 21036719 TI - Sodium butyrate with UCN-01 has marked antitumour activity against cervical cancer cells. AB - AIM: The effect of combining sodium butyrate (NaB), a histone deacetylase inhibitor, and 7-hydroxy-staurosporine (UCN-01) on cytotoxicity in human cervical carcinoma cells was evaluated. MATERIALS AND METHODS: HeLa and CaSki cells were treated using NaB alone or in combination with staurosporine (STS) or its analog UCN-01. Cytotoxicity was determined by flow cytometry and morphological assays. Apoptotic pathways were characterized by Western blotting and immunostaining. CaSki cells were also xenografted into nude mice to assess the in vivo effects of NaB/UCN-01 combination. RESULTS: Treatment with NaB and STS or UCN-01 resulted in enhanced apoptosis of cancer cells. Apoptosis involved mitochondrial pathways and overexpression of p53 and p73. In concordance, co-treatment modulated some p53/p73 downstream targets such as p21, BAX, BCL-2 and BCL-X(L), leading to increased caspase-3 and poly(ADP-ribose) polymerase cleavage. In vivo, NaB/UCN-01 combination exerted a substantial tumour growth suppression effect compared with single treatment. CONCLUSION: UCN-01 was shown to be a potentiator of NaB therapy for cervical cancer cells. PMID- 21036720 TI - Reversal of multidrug resistance in murine lymphoma cells by amphiphilic dihydropyridine antioxidant derivative. AB - BACKGROUND: Multidrug resistance, the principal mechanism by which cancer cells develop resistance to chemotherapy drugs, is a major factor in the failure of many forms of chemotherapies. AIM: The aim of the study was to investigate the effect of K-2-11 on the reversal of multidrug resistance. MATERIALS AND METHODS: The effects of amphiphilic dihydropyridine derivative K-2-11 were tested on MDR1 expressing mouse lymphoma cells and their parental control. The effects of K-2-11 with and without doxorubicin were studied by determination of cell viability, cell proliferation and production of reactive oxygen species. RESULTS: K-2-11 caused complete reversal of multidrug resistance of the MDR cells, being much more efficient than the positive control verapamil. Accordingly, the cytotoxic effects of doxorubicin were enhanced by K-2-11, both in the MDR and in parental cell line, while K-2-11 alone did not affect cell viability. K-2-11 also acted as an antioxidant, reducing the cellular generation of reactive oxygen species. CONCLUSION: Our results indicate the high potential of K-2-11 as a novel antioxidant with potent MDR-blocking ability that should be studied further for development in adjuvant anticancer treatments. PMID- 21036721 TI - Gamma-secretase inhibitors induce erythroid differentiation in erythroid leukemia cell lines. AB - BACKGROUND: Notch signaling regulates the fate of hematopoietic stem cells and leukemia cells. However, the role of Notch in erythroid differentiation remains unclear. MATERIALS AND METHODS: We examined the effects of three gamma-secretase inhibitors (GSI-IX, GSI-XII and GSI-XXI) that inhibit Notch signaling on the in vitro growth and differentiation of HEL and AA erythroid leukemia cell lines. RESULTS: GSI treatment induced morphologic erythroid differentiation and promoted hemoglobin production. GSI treatment suppressed short-term growth and colony formation, while treatment with GSI-XXI promoted the growth of AA cells. The degree of differentiation induced by each GSI roughly correlated with the reduction in HES1 mRNA expression. CONCLUSION: GSIs have potential uses in differentiation induction therapy for erythroid leukemia in the future. Before clinical use, in vitro sensitivity tests should be performed because the effects of GSIs are diverse depending upon the combination of leukemia cells and GSIs. PMID- 21036722 TI - Nanodiamond and nanoplatinum liquid, DPV576, activates human monocyte-derived dendritic cells in vitro. AB - BACKGROUND: The influence of nanoparticles on the immune system is poorly understood. It was recently shown that exposure to a mixture of nanodiamond (ND)- and nanoplatinum (NP)-coated material (DPV576-C) activates murine T-cells. This study examined the role of a dispersed aqueous mixture of ND/NP (DPV576) in activating human dendritic cells (DCs) in vitro. MATERIALS AND METHODS: Human monocyte-derived DCs were treated with DPV576 at various concentrations (50, 100 and 200 MUg/ml) for 24 hours in vitro. Activation of DCs was determined by assessing the expression of co-stimulatory and maturation markers (CD80, CD83, CD86, HLADR), production of cytokines, and induction of proliferation of naive CD4 T-cells. Expression of co-stimulatory molecules and cell proliferation were analysed by flow cytometry and cytokine secretion by ELISA. RESULTS: DPV576 treatment of DCs resulted in: (i) increased CD83 and CD86 expression on DCs, (ii) up-regulation in the levels of DC-secreted cytokines IL-6, TNF and IL-10, and (iii) increased ability to induce proliferation in CD4(+) T-cells which is associated with increased expression of T-cell activation marker CD25. CONCLUSION: Solution containing ND/NP (DPV576) activated human DCs and DCs-driven CD4 naive T-cell proliferation in vitro, which may be useful in boosting immune responses in cancer treatment. PMID- 21036723 TI - Evaluation of HER-2/neu gene amplification by fluorescence in situ hybridization and immunohistochemistry in saudi female breast cancer. AB - BACKGROUND: Amplification of the HER-2/neu oncogene and concomitant over expression of its protein are detected in approximately 18% of invasive ductal carcinoma of the breast and is associated with poor prognosis. This study tested the use of fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) to evaluate the HER-2/neu gene status and to ascertain the concordance rate between the two methods. PATIENTS AND METHODS: Eighty two tumour samples containing representative tumour were divided for testing using each assay. HER 2/neu gene amplification is scored as a ratio of HER-2/neu gene amplification to chromosome 17. The ratio should be >2.2 to be considered as positive. 20 cells should be counted and an average score taken. An extra 20 cells should be counted if the ratio is between 1.8-2.2. RESULTS: Seventy five effective samples were used. HER-2/neu gene was amplified in 19 out of 75 cases (25%) whereas, HER-2 protein, by IHC was over-expressed in 18 out of 75 cases (24%). In the 44 negative cases by IHC analysis only 7 cases (16%) of them showed amplification by FISH. Three out of 13 cases (23 %) scored as +2 showed gene amplification by FISH while 9 cases out of 18 cases (50%) were scored as +3. High concordance with FISH results 37:44 (84 %) was noted in negative cases (0/+1 cases), while lower concordance 3:13 (23 %) was seen in +2 cases. CONCLUSION: This study revealed a significant concordance between FISH results and IHC results. The study also showed that HER2/neu amplification is higher in Saudi patients than other western populations. However, due to the inherent failures of the IHC assay, FISH should always be used when the IHC results are inconclusive. The rational algorithm for HER-2/neu testing would be to perform IHC first, followed by FISH to validate equivocal IHC results. PMID- 21036724 TI - Bacillus Calmette-Guerin and BCG cell wall skeleton suppressed viability of bladder cancer cells in vitro. AB - AIM: Bacillus Calmette-Guerin (BCG) is one of therapeutic options for urothelial carcinoma (UC). The objectives of this study were to determine the direct effect of viable or heat-killed BCG and BCG cell wall skeleton (BCG-CWS) on UC cells in vitro. MATERIALS AND METHODS: UC cell lines were co-cultured with viable or heat killed BCG Immunobladder(r) (Tokyo 172 strain) and BCG-CWS. Viability of the cells, apoptosis and BrdU incorporation were estimated. RESULTS: BCG induced cell growth retardation in highly malignant UC bearing integrin alpha5beta1 (VLA5). VLA5-blocking antibody partially abrogated this effect. BCG treatment induced a modest increase in the sub-G(1) fraction of cells and a decrease of BrdU incorporation. Cell growth retardation effect of viable BCG was reproduced by both heat-killed BCG and BCG-CWS. CONCLUSION: The results indicate that VLA5 may be a biomarker of UC with sensitivity to BCG. Moreover, BCG-CWS is a promising substance which might replace BCG, preventing life-threatening complications of viable BCG treatment. PMID- 21036725 TI - Soluble MICB serum levels correlate with disease stage and survival rate in patients with oral squamous cell carcinoma. AB - BACKGROUND: Expression of ligands of natural killer group 2D (NKG2D) immunoreceptors, such as major histocompatibility complex class I-related chain A/B (MICA/B), has been proposed to play an important role in tumour immunosurveillance. Soluble forms of MICA/B are increased in sera of cancer patients and are postulated to impair antitumour immune response by downregulating expression of NKG2D immunoreceptors. Serum levels of soluble MICA have been shown to be of diagnostic significance in malignant diseases. AIMS: The potential of soluble MICB (sMICB) as a marker for oral squamous cell carcinoma (OSCC) was investigated. RESULTS: sMICB levels did not differ significantly from those in normal control individuals. However, the findings indicate that sMICB levels are significantly increased in stage IV OSCC and high sMICB levels are significantly associated with decreased survival rates in patients. PMID- 21036726 TI - Isomorph expression of BAG-1 gene, ER and PR in endometrial cancer. AB - BACKGROUND: BAG-1 isomorphs are regulating proteins with antiapoptotic action in endometrium. ERa and PRA isomorphs seem to have an important role in endometrial cancer. PATIENTS AND METHODS: We investigated the expression of BAG-1, ERa and PRA isomorphs in endometrioid adenocarcinoma and we correlated them with clinicopathological findings of the tumor. Fresh endometrial tissues were obtained from 33 patients with endometrial carcinoma and 191 paraffin-embedded tissues were analyzed by real-time PCR and immunochemistry for BAG-1, ER and PR. RESULTS: BAG-1 protein is expressed in both nucleus and cytoplasm. Grade 3 tumors were considered to have the highest intensity. Only 4 out of 79 samples showed intense expression of ERa, while 37 samples out of 72 samples strongly expressed PRA. CONCLUSION: BAG-1 nuclear isomorph appeared more frequently in grade 2 tumors than in grade 1 and 3 tumors, and the cytoplasmatic isomorph was expressed more strongly than the nuclear one. PMID- 21036727 TI - Vitamin B2 as a tracer for intraoperative pulmonary sentinel node navigation surgery. AB - BACKGROUND: We investigated whether fluorescent agents, especially vitamin B2, can act as tracers for intraoperative pulmonary sentinel node mapping. MATERIALS AND METHODS: Vitamin B2, fluorescent beads, and green fluorescent protein (GFP) were each injected into pulmonary parenchyma in 4 pigs (experiment 1). The safety of each tracer was also verified in 12 rats (experiment 2). RESULTS: Experiment 1: In all groups, the sentinel lymph node was identified in 3 out of the 4 pigs (75%). Speed of agent dispersion: vitamin B2>GFP >fluorescent beads. Level of fluorescence judged as: vitamin B2>GFP=fluorescent beads. Experiment 2: In all groups, all rats survived until sacrifice without complications. In the fluorescent beads group, the fluorescent beads remained in the blood vessels. CONCLUSION: Vitamin B2 is inexpensive, safe and easy to apply. It is anticipated that clinical application of vitamin B2 for intraoperative pulmonary sentinel node mapping will become possible. PMID- 21036728 TI - Significance of keratinocyte growth factor receptor in the proliferation of biliary tract cancer. AB - BACKGROUND/AIM: Biliary tract carcinoma (BTC) has extremely poor prognosis because of rapid cancer cell proliferation. The aim of this study was to clarify the significance of keratinocyte growth factor receptor (KGFR) in the proliferation of BTC. MATERIALS AND METHODS: The expression of KGFR in 34 surgical specimens of BTC was investigated by immunohistochemical staining. The effect of Ki23057, a small synthetic molecule that interrupts the autophosphorylation of KGFR, on the proliferation of human BTC cell lines was examined in vitro and in vivo. RESULTS: The prognosis for BTC patients with KGFR positive tumour was significantly poorer than that for those with KGFR-negative tumour. KGF significantly stimulated the proliferation of BTC cell lines. Ki23057 significantly decreased the growth of BTC cells in vitro and in vivo. CONCLUSION: KGFR may play an important role in the proliferation of BTC. KGFR phosphorylation inhibitor, Ki23057, therefore appears to be therapeutically promising in BTC. PMID- 21036729 TI - Further studies on Barretts mucosa in baboons: metaplastic glandular cells produce sialomucin. AB - BACKGROUND: In humans and in baboons, protracted gastro-esophageal reflux (GER) transforms the squamous-lined esophagus into columnar-lined (that is Barrett's mucosa, BM). Alcian blue stain (AB) is used to evidence sialomucin-producing goblet cells in human BM. AIM: To assess the frequency and distribution of sialomucin-producing cells in BM in baboons. MATERIALS AND METHODS: Sections from 137 consecutive baboon esophagi were alternatively stained with hematoxylin-eosin (H&E) and with AB (pH 2.5), without counterstain. RESULTS: Out of 137 baboons, 131 (95.6%) had BM. Columnar and intramucosal glandular cells produced sialomucin in all 131 of these animals. Many BM cells were ballooned and filled with sialomucins, despite goblet cells not being found in H&E sections. CONCLUSION: In humans, protracted GER is a disease requiring medication that may lead to BM; AB stains mainly goblet cells and occasional columnar cells in BM. In baboons, in contrast, BM is a natural postnatal process of adaptation to GER, triggered by regurgitation and rumination. AB stains all columnar and intra-mucosal glandular cells. Sialomucin-overstuffed cells were more frequent and larger in baboons than in humans. The extra load of sialomucin in BM might be an integrated part of the postnatal life-long process of adaptation to regurgitation and rumination in baboons. PMID- 21036730 TI - Overexpression of tissue inhibitor of metalloproteinase-1 gene correlates with poor outcomes in colorectal cancer. AB - Tissue inhibitor of metalloproteinase-1 (TIMP-1) is a major endogenous regulator of matrix metalloproteinases. This study examined the relation between TIMP-1 gene expression and postoperative mortality in patients with colorectal cancer (CRC). Specimens of CRC were obtained from 202 patients. The relative expression levels of TIMP-1 mRNA in cancer and in normal adjacent mucosa were measured by quantitative real-time reverse-transcriptase polymerase chain reaction. The expression level of the TIMP-1 gene was categorized as low or high according to the median value. The TIMP-1 level did not correlate with any clinicopathological feature. On Kaplan-Meier analysis, the 5-year overall survival rate was significantly lower in patients with high TIMP-1 (62.6%) than in those with low TIMP-1 (80.6%; p=0.0113). High TIMP-1 mRNA expression was associated with significantly poorer overall survival on univariate Cox regression analysis (p=0.013) and multivariate analysis (p=0.019). [corrected]. Overexpression of TIMP-1 thus correlated with poor outcomes in patients with CRC. Our results suggest that the TIMP-1 gene expression level might be a useful, independent prognostic factor in CRC. PMID- 21036731 TI - Methylation of the TFPI2 gene is frequently detected in advanced gastric carcinoma. AB - BACKGROUND: Recently, Glockner et al. identified the methylation of TFPI2 as a frequent event in human colorectal cancer using a gene expression array-based strategy. MATERIALS AND METHODS: Methylation status of the TFPI2 gene was examined in primary carcinomas and the corresponding normal tissues derived from 38 patients with gastric cancer using quantitative methylation-specific PCR (qMSP) and the correlation between the methylation status and the clinicopathological findings was evaluated. RESULTS: Aberrant methylation of the TFPI2 gene was detected in 7 out of 38 (18%) primary gastric carcinomas, suggesting that the methylation of TFPI2 is frequently observed in gastric carcinomas. The clinicopathological data were correlated with the methylation results. A significant difference was observed in maximal tumour size (p=0.0084), extent of tumour (p=0.0068), and TNM stage (p=0.0392). CONCLUSION: TFPI2 is frequently methylated in advanced gastric carcinomas. PMID- 21036732 TI - SLC34A2 as a novel marker for diagnosis and targeted therapy of breast cancer. AB - The purpose of this study was to estimate the role of the SLC34A2 gene in breast cancer. A total of 146 samples were collected from breast cancer tissues and their adjacent normal breast tissues. Reverse transcription and real-time polymerase chain reaction were used to estimate gene expression levels. There was a significantly increased gene expression of SLC34A2 (normal tissues: 6.71+/ 0.77; tumour tissues: 10.29+/-0.80) among breast cancer tissues compared with normal tissues. However, there was no significant association between overall survival and the gene expression level of SLC34A2. Moreover, a significant overexpression of CA125 (normal tissues: 7.26+/-0.62; tumour tissues: 10.51+/ 0.58) in breast cancer tissues and a significant correlation between SLC34A2 and CA125 gene expressions were found. Our results suggested SLC34A2 to be involved in the development of breast cancer; this gene may therefore be a novel marker for the detection of breast cancer and act as a target gene in therapeutic strategies. PMID- 21036733 TI - The joint effect of hOGG1 single nucleotide polymorphism and smoking habit on lung cancer in Taiwan. AB - AIM: To evaluate the association and interaction among human 8-oxoguanine DNA glycosylase 1 (hOGG1) genotypic polymorphism, smoking status and lung cancer risk in Taiwan. MATERIALS AND METHODS: The gene for hOGG1 was analyzed via polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 358 patients with lung cancer and 716 healthy controls recruited from the China Medical Hospital. RESULTS: The hOGG1 codon 326 genotypes were not differently distributed between the lung cancer and control groups (p=0.0809). However, the C allele of hOGG1 codon 326 was significantly (p=0.0198) more frequently found in controls than in cancer patients. We further analyzed the joint effect of genetics and smoking on lung cancer risk and found an interaction between hOGG1 codon 326 genotypes and smoking status. The hOGG1 codon 326 C allele-bearing genotypes were significantly associated with lung cancer risk only in the smoker group (p=0.0132), but not in the non-smoker group (p=0.06588). CONCLUSION: Our results provide evidence that the C allele of hOGG1 codon 326 may have a joint effect with smoking on the development of lung cancer. PMID- 21036734 TI - Real-time PCR: detection of oestrogen receptor-alpha and -beta isoforms and variants in breast cancer. AB - BACKGROUND: Splice variants exist for both alpha and beta oestrogen receptors (ERs). Oestrogen function results from a balance between the wild-type ERs (wt) and their variants. PATIENTS AND METHODS: Forty formalin-fixed paraffin-embedded breast cancer samples were analysed by real-time PCR using ERalpha primer sets detecting wt and exon-deleted 3, 5, 6 and 7 variants. The ERbeta primer sets detected wt ERbeta1 and ERbeta2 and ERbeta5 variants. At the end of the PCR cycles, a dissociation curve was generated showing the peaks for each sample at specific melting temperatures (Tm); finding more than one peak indicated the presence of variants. RESULTS: Many samples expressed both wt ER isoforms and their variants. The Tm value served as a cut-off point for determination of wt versus variant ER expression. CONCLUSION: This method of detection of wt and variant ER could help in patient selection for anti-oestrogen therapy and in monitoring response to therapy. PMID- 21036735 TI - CRIM1 is expressed at higher levels in drug-resistant than in drug-sensitive myeloid leukemia HL60 cells. AB - AIM: The aim of this study was to explore possible differences in the mRNA expression levels of CRIM1, SMAD5, BMP4 and BMP7 in sensitive (S) and multidrug resistant (R0.5) myeloid leukemia HL60 cells. MATERIALS AND METHODS: HL60S and HL60R0.5 cells were exposed to daunorubicin (DNR) or cytarabine (Ara-C). RESULTS: Baseline levels of CRIM1 were found to be 15-fold higher in HL60R0.5 than in HL60S. Sixteen hours of exposure to DNR resulted in a 5.6-fold increase in CRIM1 levels in HL60S. Exposure to either DNR or Ara-C resulted in modest increases in CRIM1 levels in HL60R0.5. Similarly, baseline levels of SMAD5 and BMP4 were higher in HL60R0.5 than in HL60S cells. Analysis of the drug SMAD5-resistance marker permeability-glycoprotein (Pgp) revealed that CRIM1 and Pgp exhibit a covariance pattern of expression. CONCLUSION: This study demonstrated that CRIM1 is expressed at high levels in resistant leukemia cells, indicating that CRIM1 may play a role in drug-resistance. PMID- 21036736 TI - Clinicopathological significance of p53, hypoxia-inducible factor 1alpha, and vascular endothelial growth factor expression in colorectal cancer. AB - BACKGROUND: The principal objective of this study was to evaluate the prognostic significances of p53, hypoxia inducible factor-1 alpha (HIF-1alpha), and vascular endothelial growth factor (VEGF) expression in colorectal cancer. MATERIALS AND METHODS: The tumor tissues of 311 patients with colorectal carcinoma that had undergone potentially curative resections were immunohistochemically assessed using monoclonal antibodies against p53, HIF-1alpha, and VEGF. RESULTS: Positivity rates of p53, HIF-1alpha, and VEGF were 42.4%, 63.0%, and 56.6%, respectively. HIF-1alpha expression in tumor tissues was determined to be correlated significantly with the expression of VEGF (p=0.040), and depth of invasion (p=0.019). Multivariate analysis demonstrated that HIF-1alpha was independently associated with poor overall survival (p=0.002). CONCLUSION: HIF 1alpha expression is associated with VEGF expression and angiogenesis in colorectal carcinoma. Additionally, the expression of HIF-1alpha in tumor tissue is associated with angiogenesis and poor overall survival in patients with colorectal cancer. PMID- 21036737 TI - Differential suppression of proliferation in MCF-7 and MDA-MB-231 breast cancer cells exposed to alpha-, gamma- and delta-tocotrienols is accompanied by altered expression of oxidative stress modulatory enzymes. AB - Tocotrienols belong to the vitamin E family of chemicals known to have potent anti-proliferative and apoptotic activities against a variety of cancer cells with little to no comparable influence on the normal cells. Whether tocotrienols control the expression of phase II antioxidant enzymes in the context of their anti-carcinogenic mechanisms has not been investigated. The present studies were performed to test whether the differential growth inhibition resulting from exposure to alpha-, gamma- and delta-tocotrienols in estrogen receptor-positive human MCF-7 and estrogen receptor-negative MDA-MB-231 breast cancer cells might be accompanied by changes in phase II antioxidant enzymes. Cell proliferation and clonogenicity in both cell lines were significantly inhibited by gamma- and delta tocotrienols with little affect when cells were similarly exposed to alpha tocotrienol, at doses up to 10 MUM. The expression and activity of several antioxidant enzymes in 10 MUM tocotrienol-treated cells were determined by Western blot and biochemical assays. In MDA-MB-231 cells, delta- was more active than alpha- or gamma-tocotrienols in up-regulating glutathione peroxidase; however, the three tocotrienols had comparable activity in inducing thioredoxin. In MCF-7 cells, expression of quinone reductase 2 and thioredoxin was increased by gamma- and delta-tocotrienols, whereas quinone reductase 1 was unaffected by exposure to the tocotrienols. The tocotrienols also did not affect the expression and activity of superoxide dismutase in both MCF-7 and MDA-MB-231 cells, but increased catalase activity concomitant with slight reduction in the catalase expression. In MDA-MB-231 cells, treatment by tocotrienols led to several fold increase of NRF2 expression marked by corresponding decrease in KEAP1 levels. By contrast, no significant change in NRF2 and KEAP1 levels was observed in MCF-7 cells. These studies demonstrate that different tocotrienols show distinct and selective activity in regulating the NRF2-KEAP1, in coordination with the induced expression of cytoprotective oxidative stress modulatory genes and regulation of proliferation in breast cancer cells. PMID- 21036738 TI - Up-regulation of fibronectin and tissue transglutaminase promotes cell invasion involving increased association with integrin and MMP expression in A431 cells. AB - In human tumors, fibronectin (FN) expression is positively associated with tumor metastatic potential and matrix metalloproteinase (MMP) secretion. Additionally, tissue transglutaminase (TG2) is implicated as playing an important role in tumor progression, and acts as a co-receptor for integrin-mediated cell binding to FN. This study explored the involvement of FN and TG2 in cancer cell metastasis using the recently established highly invasive A431-III subline. A431-III cells expressed significantly higher levels of FN and TG2 as compared to the parental line (A431-P). Knockdown of endogenous FN by small interfering RNA (siRNA) resulted in dramatic suppression of the migratory and invasive activity, and the secreted MMP-9 activity (but not MMP-2) in A431-III subline. Exogenous administration of FN to A431-III cells also increased the secreted activity of MMP-9 but not MMP-2. Interestingly, knockdown of TG2 by siRNA dramatically reduced the cell attachment, migration and invasion, and the secretion of MMP-9 and MMP-1 (but not MMP-2 and MMP-3) in A431-III cells as compared to A431-P cells. Furthermore, A431-III cells exhibited increased association of integrin beta1 and beta3 with FN and TG2, and knockdown of TG2 markedly suppressed integrin beta1 interaction with FN. Together, this study suggests that FN and TG2 facilitate the metastatic activity of A431 tumor cells, and this may be partly attributed to TG2 enhancement of the association of FN and beta integrin. In addition, the combined targeting of TG2 and FN may be an effective therapeutic strategy for cancer displaying increased expression of both proteins. PMID- 21036739 TI - The novel quinolone CHM-1 induces DNA damage and inhibits DNA repair gene expressions in a human osterogenic sarcoma cell line. AB - 20-Fluoro-6,7-methylenedioxy-2-phenyl-4-quino-lone (CHM-1) has been reported to induce cell cycle arrest and apoptosis in many types of cancer cells. However, there is no available information to show CHM-1 affecting DNA damage and expression of associated repair genes. Herein, we investigated whether or not CHM 1 induced DNA damage and affected DNA repair gene expression in U-2 OS human osterogenic sarcoma cells. The comet assay showed that incubation of U-2 OS cells with 0, 0.75, 1.5, 3 and 6 MUM of CHM-1 led to a longer DNA migration smear (comet tail). DNA gel electrophoresis showed that 3 MUM of CHM-1 for 24 and 48 h treatment induced DNA fragmentation in U-2 OS cells. Real-time PCR analysis showed that treatment with 3 MUM of CHM-1 for 24 h reduced the mRNA expression levels of ataxia telangiectasia mutated (ATM), ataxia-telangiectasia and Rad3 related (ATR), breast cancer 1, early onset (BRCA1), 14-3-3sigma (14-3-3sigma), DNA-dependent serine/threonine protein kinase (DNA-PK) and O(6)-methylguanine-DNA methyltransferase (MGMT) genes in a time-dependent manner. Taken together, the results indicate that CHM-1 caused DNA damage and reduced DNA repair genes in U-2 OS cells, which may be the mechanism for CHM-1-inhibited cell growth and induction of apoptosis. PMID- 21036740 TI - Inhibition of Myc effectively targets KRAS mutation-positive lung cancer expressing high levels of Myc. AB - Myc is an oncogenic transcription factor that promotes tumorigenesis. Recently, a dominant negative form of Myc (Omomyc) was shown to cause regression of lung tumors in a mouse model of lung cancer caused by KRAS mutation, suggesting that Myc might be a potential therapeutic target to treat the KRAS lung cancer. However, it is not yet known whether Omomyc can also inhibit the growth of human lung tumors that carry a similar KRAS mutation. In the present study, we demonstrate that Omomyc induces cell death of KRAS-mutated human lung adenocarcinoma A549 cells in vitro and in vivo. However, Omomyc does not induce cell death in human lung adenocarcinoma H441 cells that also carry the KRAS mutation. Interestingly, A549 cells express high levels of Myc, while H441 cells do not. Co-expression of exogenous Myc with Omomyc in H441 cells induces cell death, indicating that Omomyc requires high levels of Myc to induce cell death in KRAS mutation-positive lung adenocarcinoma. Here, we show for the first time that KRAS mutation-positive lung cancer displaying high levels of Myc could be treated by inhibiting Myc transactivation function. PMID- 21036741 TI - Antitumour and cytogenetic effects of modified steroidal derivatives of propenoic acid: in vivo/in vitro studies. AB - BACKGROUND: Modified steroidal derivatives (PK11-PK14) of p-bis(2 chloroethyl)aminophenyl propenate (PK15) were used to study their antitumour activity on Lewis lung carcinoma (LLC) and their effect on sister chromatid exchanges (SCEs) and human lymphocyte proliferation kinetics. MATERIALS AND METHODS: LLC was tested in this study. C57BL mice were used for in vivo chemotherapy evaluation and the antitumour activity was assessed. Lymphocyte cultures were used to study the genotoxic effect in vitro. RESULTS: PK15 and PK11 were the most effective against LLC, causing significant inhibition of tumour growth. PK11 and PK15 induced significant increase in SCE rates. A correlation was observed between the cytogenetic effect and the antitumour effectiveness. CONCLUSION: The order of the antitumour effectiveness of PK11-PK15 resembled the order of the cytogenetic damage induced by the same compounds in vitro. PMID- 21036742 TI - The joint effect of hOGG1 single nucleotide polymorphism and betel quid chewing on oral cancer in Taiwan. AB - AIM: To evaluate the association and interaction among hOGG1 genotypic polymorphism, betel quid chewing status and oral cancer risk in Taiwan. MATERIALS AND METHODS: The well-known polymorphic variants of hOGG1, codon 326, were analyzed in association with oral cancer susceptibility, and discussed regarding its joint effect with individual habits on oral cancer susceptibility. In total, 620 patients with oral cancer and 620 healthy controls recruited from the China Medical Hospital were analyzed by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). RESULTS: The hOGG1 codon 326 genotypes were differently distributed between the oral cancer and control groups (p=0.0266) and the C allele of hOGG1 codon 326 was significantly (p=0.0046) more frequently found in cancer patients than in controls. We further analyzed the joint effects of gene variants and habits on oral cancer risk and found an interaction between hOGG1 codon 326 genotype and betel quid chewing status. The association of the C allele for hOGG1 codon 326 with oral cancer risk was found to be significant only in the betel quid chewer group (p=0.0149), not in the non chewer group (p=0.8028). CONCLUSION: Our results provide evidence that the C allele of hOGG1 codon 326 may have a joint effect with betel quid chewing on the development of oral cancer. PMID- 21036744 TI - EGFR-activating mutations are not present in breast tumors of Japanese patients. AB - BACKGROUND: Despite advances in treatment, recurrent breast cancer remains a lethal disease. The epidermal growth factor receptor family has been suggested to play a role in breast cancer. However, no investigations of the frequency of EGFR mutation and the potential role of EGFR tyrosine kinase inhibitor (TKI) in Japanese patients with breast cancer. MATERIALS AND METHODS: Tumor specimens were collected from 84 breast cancer patients who underwent surgery. Polymerase chain reaction-based methods were used to examine EGFR-activating mutations (exon 19 and 21). RESULTS: Activating mutations in the tyrosine kinase domain of EGFR were not identified in any of the tumors. CONCLUSION: EGFR-activating mutations were not present in the Japanese breast cancer series studied here. Therefore, unlike lung cancer, EGFR tyrosine kinase inhibitors are unlikely to provide any benefit for Japanese breast cancer patients. PMID- 21036743 TI - Molecular predictors of combination targeted therapies (cetuximab, bevacizumab) in irinotecan-refractory colorectal cancer (BOND-2 study). AB - BACKGROUND: To test whether intratumoral gene expression levels and germline polymorphisms predict clinical outcome in metastatic colorectal cancer (mCRC) patients treated with cetuximab and bevacizumab plus irinotecan (CBI) vs. cetuximab and bevacizumab (CB)(BOND2). PATIENTS AND METHODS: Genomic DNA was extracted for genotyping from 65 patients (31: CBI arm and 34: CB arm). Thirty five patients had tissue samples available for the gene expression assay (18: CBI arm and 17: CB arm). RESULTS: High intratumoral gene expression levels of EGFR, VEGFR2 and NRP1 were associated with longer overall survival (OS) in patients receiving combined monoclonal antibodies with or without irinotecan. FCGR3A V158F, CyclinD1 A870G and EGFR R497K polymorphisms are associated with clinical outcome in patients received combined cetuximab and bevacizumab. CONCLUSIONS: Intratumoral gene expression levels of EGFR, VEGFR2 and NRP as well as polymorphisms in FCGR3A, CyclinD1 and EGFR could predict clinical outcome in mCRC patients enrolled in BOND2, independent of KRAS mutation status. PMID- 21036745 TI - L-type amino-acid transporter 1 expression predicts the response to preoperative hyperthermo-chemoradiotherapy for advanced rectal cancer. AB - AIM: To evaluate whether expression of L-type amino acid transporter 1 (LAT1) in pretreatment rectal cancer biopsies is predictive of tumour response to neoadjuvant hyperthermo-chemoradiotherapy (HCRT). PATIENTS AND METHODS: Forty four patients with rectal adenocarcinoma who received neoadjuvant HCRT were investigated. LAT1 expression was immunohistochemically evaluated using pretreatment biopsies. The operation was performed after 2-3 months following HCRT and each resected specimen was graded by the histological criteria of the Japanese Classification of Colorectal Carcinoma. RESULTS: A positive LAT1 expression was recognized in 50.0% (22/44) of patients. Resected specimens were divided into 2 groups according to the histological grading criteria: good response (n=29) and poor response (n=15). LAT1-negative tumours had an 81.8% probability of good response and 18.2% probability of poor response. LAT1 expression showed marginally significant association with response to HCRT (p=0.05). CONCLUSION: LAT1 may be a useful predictive marker of response to HCRT in rectal cancer. PMID- 21036746 TI - Concordant analysis of KRAS status in primary colon carcinoma and matched metastasis. AB - KRAS somatic mutations are the main predictive factor for non response to EGFR targeted monoclonal antibodies in metastatic colorectal cancer (mCRC) patients. We compared KRAS mutational status in the primary tumour and the corresponding metastases (1 to 4 sites) in 38 mCRC patients. KRAS mutational status was analysed using direct sequencing, SNAPShot multiplex PCR and Scorpion Taqman PCR analysis. Results showed 54% of primary tumours had KRAS mutations. A concordance of 97% between primaries and metastatic sites was observed. A tumour heterogeneity was also demonstrated in 5% of mCRC. One case with three different primary tumours harboured three different KRAS mutations, and only one was represented in the unique metastasis of this patient. We concluded there was a high concordance in the KRAS status between the primary tumour and metastases. More than one informative block and more sensitive assay may increase the accuracy of KRAS status determination. PMID- 21036747 TI - Weekly chemoradiation (docetaxel/cisplatin) followed by surgery in stage III NSCLC; a multicentre phase II study. AB - BACKGROUND: This prospective study analyzed the feasibility and efficacy of weekly concurrent chemoradiation (docetaxel/cisplatin) followed by surgery. The primary endpoint was radiological response. PATIENTS AND METHODS: Six chemotherapy (docetaxel/cisplatin) cycles were administered on days 1, 8, 15, 22, 29 and 36 with concurrent thoracic radiotherapy in fractions of 1.8 Gy, to a total dose of 45 Gy. Patients underwent surgery depending on results of invasive mediastinal re-staging. RESULTS: Forty-two out of 45 NSCLC stage III patients were evaluable. Nineteen patients showed partial/complete response (46%), 14 stable disease (34%) and eight (20%) progressive disease. Toxicity was mild. The 30-day postoperative mortality was 4.2%. Twenty-four patients (59%) proceeded to surgery and 20 (49%) underwent a complete resection (R0). CONCLUSION: Weekly concurrent chemoradiation (docetaxel/cisplatin) in stage III NSCLC results in a radiological response rate of 46% and mediastinal downstaging in 56%. Complete resection in downstaged patients was achieved in 49% of all patients. PMID- 21036748 TI - Use of paclitaxel for advanced ovarian cancer in clinical practice: analysis of 541 patients. Results from a German multi-centre observational study. AB - Paclitaxel is one of the most common antitumour agents paclitaxel for the treatment of primary and relapsed ovarian cancer. Based on a German multicentre observational study, this article reflects the use of paclitaxel in German daily clinical practice. PATIENTS AND METHODS: Data for a total of 541 patients in Germany were analysed, including 315 patients with primary ovarian cancer and 226 patients treated with paclitaxel with relapsed ovarian cancer. RESULTS: The mean age was 61.2 years, ranging from 22 to 85 years. No unexpected toxicities were ascertained. In general, grade III/IV haematological toxicities were rare. Only 15% of the patients suffered from grade III/IV leucopenia and 5% from thrombocytopenia. Alopecia and polyneuropathy were the most frequent non haematological side-effects noticed. Response evaluation was provided in 183 patients with primary ovarian cancer (CR 39.8%, of these achieved a complete response (CR), and 27.9% a partial response (PR), resulting in an overall response rate (ORR) of 67.7%. In 13.7%, stable disease (SD) and in 19.7%, tumour progression (PD) were documented. In 196 patients with recurrent ovarian cancer, response evaluation was provided. A total of 28.6% of the patients achieved a CR, and 31.6% a PR, which produced an ORR of 60.2%. In 33.2%, SD and in 6.6%, PD were documented. CONCLUSION: Paclitaxel is broadly used in the management of patients with primary and relapsed ovarian cancer. The toxicity profile observed seems to be within the range of the results of clinical phase-III studies. The doses applied and the schedules based on the official recommendation of the working groups seem to have been influenced by international studies. PMID- 21036749 TI - Impact of tumor biology, particularly triple-negative status, on response to pre operative sequential, dose-dense epirubicin, cyclophosphamide followed by docetaxel in breast cancer. AB - BACKGROUND: The central objective of this study was to determine the predictive impact of several established tumor biological factors (PgR, ER, HER2 and Ki-67) on response to pre-operative chemotherapy in primary breast cancer. PATIENTS AND METHODS: 59 primary M0 breast cancer patients received pre-operative sequential dose-dense epirubicin and cyclophosphamide followed by docetaxel (19 patients at dosage 100 mg/m(2), 40 patients at 75 mg/m(2)). RESULTS: Pathological complete remission (pCR) occurred in 17 patients (29%) and at least partial remission in 42 (71%). Higher proliferation (Ki-67) and lack of hormone receptors (either or both) were significant predictive factors for pCR; moreover, 8/11 (73%) patients with triple-negative tumors (HER2(-)/ER(-)/PgR(-)) had pCR (p=0.001). Breast conserving surgery was achieved in 46/59 patients (78%). Hand-foot syndrome occurred in 12/19 patients treated at the higher docetaxel dosage but only 1/40 of the remaining patients. Higher docetaxel dosage was associated with improved pCR in the non-triple-negative subgroup. CONCLUSION: The tumor biology of hormone receptor-negative, especially triple-negative, and highly proliferating breast cancer is associated with strongly positive response to dose-dense, pre-operative epirubicin/cyclophosphamide/docetaxel chemotherapy. PMID- 21036750 TI - Assessing risk and mortality of venous thromboembolism in pancreatic cancer patients. AB - BACKGROUND: Venous thromboembolism (VTE) is associated with cancer. Cancer patient with thromboembolism have poorer prognosis. This study assessed the risk and mortality in pancreatic cancer patients who develop VTE. PATIENTS AND METHODS: A retrospective chart review was performed of 201 patients with pancreatic cancer. RESULTS: VTE was observed in 58 (28.9%) patients, 37/58 had deep vein thrombosis (DVT), 11/58 pulmonary embolism (PE) and 10/58 had both. Twenty-six out of 107 patients with tumor of head of the pancreas developed VTE (24%), compared to half of the patients with body of the pancreas involvement (11 22). Stage IV was defined in 99 patients, 39/99 had VTE (39%). Median survival time was 14.95 months for patients without VTE compared to 13.04 months with VTE. CONCLUSION: Patients with body of the pancreas and stage IV tumors had increased risk of developing VTE. There was no survival difference between patients with VTE compared to those without. PMID- 21036751 TI - Atlanto-occipital ligament calcification: a novel sign in nevoid basal cell carcinoma syndrome. AB - BACKGROUND: The nevoid basal cell carcinoma syndrome (NBCCS), first described by Gorlin and Goltz in 1960, is a hereditary autosomal dominant disease with high penetrance and variable expressivity. Almost 70% of patients with NBCCS have some degree of craniofacial anomaly. Among these, the presence of ectopic calcification have been reported but Atlanto-occipital ligament calcification has never been described. Therefore this investigation was carried out to determine the prevalence of atlanto-occipital ligament calcification on lateral x-ray of NBCCS patients aiming to assess the effectiveness of this sign in NBCCS diagnosis. PATIENTS AND METHODS: Lateral and frontal cephalometric radiographs of 18 patients (11 males and 7 females), aged 8-61 years, with the diagnosis of NBCCS were evaluated for the presence of intracranial calcifications (diaphragma sellae and falx cerebri) and or calcification of the atlanto-occipital ligament. RESULTS: A total of 11 patients presented calcification of atlanto-occipital ligament to various degrees and in three cases this represented the only sign of ectopic calcification. When compared to the other two sites of ossification, atlanto-occipital ligament calcification had a similar prevalence. CONCLUSION: The calcification of the atlanto-occipital ligament should be considered in addition to the other major criteria for NBCCS diagnosis. PMID- 21036753 TI - Late metastasis of gastrointestinal stromal tumour to the oral cavity. AB - This report describes the diagnosis and treatment of a metastasis of a gastrointestinal stromal tumour (GIST) to the oral cavity in a 64-year-old female, 14 years after treatment for a gastric primary and 11 years after partial hepatectomy for regional recurrence. The metastasis grew slowly in the buccal soft tissues and became symptomatic by intraoral extension. Positron-emission tomography combined with computed tomography depicted a solitary space-occupying lesion in the right buccal region with high standardized uptake values. Surgical exploration revealed a ball-shaped firm tumour mass adhering to the adjacent tissues that was completely resected. Subsequent healing was uneventful. Six months following ablative surgery the patient was in good general condition. There were neither signs of local tumour recurrence nor further distant spread. However, the patient is now under continuous medication with imatinib. GIST metastases to the head and neck region are very rare. Two recent case reports about head and neck metastases of GIST showed a predilection for bone. This metastasis was solely located in the oral soft tissues. PMID- 21036752 TI - Dual role of RASSF1 as a tumor suppressor and an oncogene in neuroendocrine tumors of the lung. AB - BACKGROUND: Little is known about the dual role of RAS-association domain family 1 (RASSF1) gene at 3p21.3 in neuroendocrine tumors (NET) of the lung. MATERIALS AND METHODS: Twenty typical carcinoids (TC), 11 atypical carcinoids (ATC), 11 large cell neuroendocrine carcinomas (LCNEC) and 16 small cell lung carcinomas (SCLC) were analyzed for RASSF1 promoter methylation, mRNA and protein expression, and loss of 3p21.3 locus. RESULTS: Promoter 1 was hypermethylated in NET but not in paired non-neoplastic lung tissues nor in 20 control NSCLC, with the degree of hypermethylation paralleling tumor grade. RASSF1 A/E isoform mRNA but not protein expression was lost in most NET compared to NSCLC or non neoplastic tissues. The relationship between methylation level and mRNA or protein loss varied by NET type, with significant correlation for decreasing RASSF1 A protein in ACT, and marginal correlation for down-regulated RASSF 1 A/E mRNA in TC, this suggesting a non linear regulation by methylation in NET. No promoter 2 methylation was detected in NET; however, up-regulation of its RASSF1 C transcript emerged as an adverse prognostic factor in the LCNEC/SCLC group. A correlation was found between 3p21.3 allelic loss and decrease of RASSF1 A/E mRNA (p=0.023) and protein (p=0.043) expression in ATC, suggesting that 3p21.3 allelic loss contributed to the loss of gene expression. CONCLUSION: RASSF1 A/E is likely to act as a tumor suppressor gene in most pulmonary NET, and RASSF1 C as an oncogene in high-grade tumors. PMID- 21036754 TI - Clinical and molecular determinants of survival in pancreatic cancer patients treated with second-line chemotherapy: results of an Italian/Swiss multicenter survey. AB - BACKGROUND: Increased knowledge about the treatment of pancreatic cancer has influenced the management of locally advanced and metastatic disease. Nonetheless, prognosis remains dismal (24%, 1-year survival). The impact on overall survival (OS) of second-line therapy has not been clarified and the use of platinum salts and/or fluoropyrimidines is hotly debated. It is the hope that future treatment can be tailored to predict chemosensitivity in order to improve outcomes in patients with locally advanced and metastatic pancreatic cancer. Since DNA-damaging agents could be one therapeutic option, a retrospective multicenter study was performed to evaluate the efficacy of salvage treatment with the hypothesis that levels of the DNA repair gene excision repair cross complementing 1 (ERCC1) could influence OS. PATIENTS AND METHODS: In a population of 160 patients treated with fluoropyrimidine-based second-line chemotherapy, expression levels of ERCC1 were determined by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR). In 108 patients with locally advanced and metastatic pancreatic cancer treated with either fluoropyrimidines and platinum salts (group A=58) or fluoropyrimidines alone (group B=50), ERCC1 levels were correlated with OS, time to progression and response to chemotherapy. RESULTS: Median survival was significantly higher in group A with low ERCC1 levels [11.9 versus 9.9 months; p <= 0.05] (median follow-up 24 months). Moreover in the same group, a trend towards longer time to progression was observed. No differences in OS were observed when ERCC1 was studied (low versus high) in patients not treated with platinum salts. On multivariate analysis of pretreatment prognostic factors, ERCC1 emerged as an independent predictive factor for OS. CONCLUSION: The results of this study indicate that ERCC1 may predict survival in pancreatic cancer patients treated by platinum and fluoropyrimidine as second-line chemotherapy. PMID- 21036755 TI - Prognostic impact of microsatellite instability in colorectal cancer patients treated with adjuvant FOLFOX. AB - BACKGROUND: Colorectal cancer (CRC) patients whose tumours have microsatellite instability (MSI) do not benefit from adjuvant 5-fluorouracil. However, the predictive value of MSI is not known for FOLFOX, now recommended in adjuvant setting. PATIENTS AND METHODS: MSI phenotype was assessed by the pentaplex method. Three-year relapse and disease-free survival (DFS) of patients treated for CRC with FOLFOX 4 in an adjuvant setting were compared according to MSI phenotype. RESULTS: A total of 105 patients (19 MSI, 86 microsatellite stable, MSS) were included. Stage II patients more frequently exhibited MSI (58%) than MSS (21%); (p=0.002). Patients with MSI relapsed significantly less than those with MSS (10.5% vs. 35.0%; p=0.04). DFS was similar for MSI and MSS (p=0.1). In univariate analysis, stage (p=0.0006) and MSI status (p=0.017) were significant predictors of DFS. CONCLUSION: MSI status was associated with significantly fewer relapses and a better prognosis. FOLFOX4 did not alter survival of patients with MSI and can be administered to them. PMID- 21036756 TI - Life stress due to losses and deficit in childhood and adolescence as breast cancer risk factor: a prospective case-control study in Kuopio, Finland. AB - BACKGROUND: To our knowledge, the associations between the life stress due to losses and deficit at childhood and adolescence and the risk of breast cancer are rarely considered together in a prospective study. MATERIALS AND METHODS: This study is an extension of the Kuopio Breast Cancer Study. Women with breast symptoms were referred by physicians to the Kuopio University Hospital (Finland) and were asked to participate in this study. These women (n=115) were interviewed, and all study variables were obtained before any diagnostic procedures were carried out, so neither the investigator nor the participants knew the final diagnosis of breast symptoms at the time of the interview. The research method used was the semistructured in-depth interview method. The investigator used the Montgomery-Asberg depression rating scale (MADRS) to evaluate the depression of the study participants. All participants were also asked to complete standardized questionnaires (Beck depression inventory and Spielberger trait inventory). RESULTS: The clinical examination and biopsy showed breast cancer in 34 patients, benign breast disease in 53 patients, and 28 individuals were shown to be healthy. The BC group had significantly higher mean score for the deficit in childhood than the BBD and HSS groups (p<0.05). The women in the BC group had almost significantly higher mean scores for the loss of social status in childhood than the women in the BBD and HSS groups (p=0.05). The BC group had also significantly more severe deficit in childhood than the BBD and HSS groups (p=0.02). The results indicated that breast cancer patients tended to have more life stress due to losses and deficit in childhood and adolescence than BBD and HSS groups. CONCLUSION: The results of this study support a weak association between life stress due to losses and deficit in childhood and adolescence and breast cancer risk. However, the biological explanation for such an association is unclear and it might be that stress due to losses and deficit impacts indirectly on breast cancer risk, affecting behaviour, or directly on the hypothalamic-pituitary-adrenal axis and autonomic nervous system functioning. PMID- 21036757 TI - TS, DHFR and GARFT expression in non-squamous cell carcinoma of NSCLC and malignant pleural mesothelioma patients treated with pemetrexed. AB - BACKGROUND: Recently, pemetrexed (PEM), a new generation antifolate, has been used for the treatment of patients with advanced non-squamous cell carcinoma (SQ) of non-small cell lung cancer (NSCLC) and malignant pleural mesothelioma (MPM). However, no useful markers for selecting appropriate candidates exist at present. MATERIALS AND METHODS: Tumor specimens were collected from 5 lung non-SQ and 8 MPM patients who underwent surgery and received PEM. Real-time PCR and immunohistochemical (IHC) staining of the primary tumor were used to analyze the mRNA and protein expressions of thymidylate synthase (TS)/dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT), and to compare the expression status and clinical outcomes. RESULTS: TS, DHFR, and GARFT mRNA levels had a median value of 2.39, 1.70, and 1.40 in non-SQ samples of NSCLC patients. The TS and DHFR protein levels had a mean total score of 2 and 4 in non SQ of NSCLC patients. TS, DHFR, and GARFT mRNA levels had a median value of 5.55, 3.73, and 3.52 in MPM patients. TS and DHFR protein levels had a mean total expression score of 1 and 3 in MPM patients. No significant correlation was identified between the expression levels of TS/DPD/GARFT mRNA and clinical response for the non-SQ of NSCLC and MPM patients treated with PEM. CONCLUSION: TS, DHFR, and GARFT mRNA and protein expression may not be useful markers for predicting clinical response in Japanese patients with non-SQ of NSCLC and MPM. Further investigations are necessary in order to develop biomarkers to determine the clinical benefits of PEM treatment. PMID- 21036758 TI - Metronomic oral cyclophosphamide prednisolone chemotherapy is an effective treatment for metastatic hormone-refractory prostate cancer after docetaxel failure. AB - BACKGROUND: There is currently no standard of treatment for patients with hormone refractory prostate cancer (HRPC) after failure of docetaxel-based chemotherapy. The purpose of this study was to assess the anticancer activity and tolerance of metronomic cyclophosphamide prednisolone combination in this setting. PATIENTS AND METHODS: From 2005 to 2010, patients with HRPC who failed at least docetaxel based chemotherapy were proposed metronomic cyclophosphamide-prednisolone regimen, and were prospectively registered. Twenty-three patients received 50 mg cyclophosphamide and 10 mg prednisolone per os daily until disease progression. Treatment tolerance and efficacy on PSA decrease and pain were studied. RESULTS: Metronomic cyclophosphamide prednisolone was safe, well tolerated, and demonstrated interesting clinical activity, yielding a prostate specific antigen decrease by >=50% in 26% of patients and decrease by >=30% in 48% of patients, but also favorable palliative effects on pain in 43% of patients. The median progression-free survival was 6 months (95% CI: 4-8 months) and the median overall survival was 11 months (95% CI: 7-19 months). CONCLUSION: For this patient population, low dose metronomic cyclophosphamide prednisolone might be a viable alternative. Its convenient oral administration, low cost, and lack of toxicity justify further studies alone, or in combination with other agents in HRPC patients. PMID- 21036760 TI - A retrospective analysis of non-platinum-based first- and second-line chemotherapy in patients with advanced non-small cell lung cancer. AB - BACKGROUND: Platinum-based chemotherapy represents the standard of care for advanced non-small cell lung cancer (NSCLC) while non-platinum-based regimens are frequently administered in patients with relapse. A retrospective analysis of the sequence administration of these regimens in the first- and second-line setting was performed. PATIENTS AND METHODS: The records of patients enrolled in the Hellenic Oncology Research Groups's randomized advanced NSCLC trials from February 1997 to September 2006 were retrospectively reviewed. The efficacy of non-platinum-based chemotherapy administered as first- or second-line treatment (n=94, cohort A) was compared to that of non-platinum-based first-line followed by platinum-based second-line chemotherapy (n=267, cohort B), and the reverse sequence (n=123, cohort C). RESULTS: The objective response rate (ORR) to first line chemotherapy was higher in cohort C compared to cohort A (45.5% vs. 25.5%, respectively, p=0.002) and cohort B (45.5% vs. 21.3%, p=0.0001). The ORR to second-line therapy was 17%, 13.1% (p=0.349) and 7.3% (p=0.027) in cohorts A, B and C, respectively. Time to progression and the overall survival were comparable among the three cohorts in both first- and second line therapy. CONCLUSION: Platinum-based first-line chemotherapy improved response rate compared to non platinum-based regimens; however, the overall survival was comparable, irrespective of the sequence administration of these regimens is the first- and second-line setting. PMID- 21036759 TI - Irinotecan/fluorouracil/leucovorin or the same regimen followed by oxaliplatin/fluorouracil/leucovorin in metastatic colorectal cancer. AB - BACKGROUND: This study reports the long-term follow-up of patients with metastatic colorectal cancer (CRC) participating in a randomised phase II study that compared the efficacy and toxicity of the combination of irinotecan (IRI), fluorouracil (FU) with leucovorin (LV) (arm A) versus sequential chemotherapy with IRI plus FU/LV followed by oxaliplatin (OXA) plus FU/LV (arm B) as first line therapy. MATERIALS AND METHODS: Intent-to-treat analysis was performed on 417 patients (211 in arm A and 206 in arm B). Treatment schedules of weekly IRI 80 mg/m(2) or OXA 45 mg/m(2) plus LV 200 mg/m(2) immediately followed by intravenous bolus FU 450 mg/m(2) for 6 weeks were followed by a 2-week rest period. Treatment continued for 4 cycles. Patients in arm A were treated with IRI/FU/LV for 4 cycles, while patients in arm B were initially treated with IRI/FU/LV for 2 cycles followed by sequential administration of 2 cycles of OXA/FU/LV. RESULTS: No significant difference emerged in overall response rate or overall survival. There was a difference in progression-free survival (median, 7.3 versus 8.2 months, p=0.040) in favour of arm B. Toxicity profiles were similar in both arms. CONCLUSION: IRI/FU/LV and IRI/FU/LV followed by OXA/FU/LV showed comparable activity with a manageable toxicity profile. PMID- 21036761 TI - Cytokeratin 19 fragment/carcinoembryonic antigen ratio in pleural effusion is a useful marker for detecting malignant pleural mesothelioma. AB - BACKGROUND: The clinical utility of tumour markers in pleural effusion is still controversial with regard to the efficient detection of malignant pleural mesothelioma (MPM). PATIENTS AND METHODS: The levels of carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA 21-1) were retrospectively studied in pleural effusion of unknown origin in patients who had undergone medical thoracoscopy under local anaesthesia. RESULTS: The study included 134 patients (103 men and 31 women); among them, 33 had MPM. The level of pleural effusion CYFRA 21-1 and the CYFRA 21-1/CEA ratio were significantly different between MPM and other diseases (p<0.01). The sensitivity and specificity of the pleural effusion CYFRA 21-1/CEA ratio were 84.8% and 80.2%, respectively, when the CYFRA 21-1/CEA ratio cut-off value determined by receiver operating characteristic curve analysis was 19.1. CONCLUSION: MPM should be suspected when the CYFRA 21 1/CEA ratio in pleural effusion is greater than 19.1. PMID- 21036762 TI - Disease-free interval after primary treatment predicts prognosis of recurrent endometrial carcinoma. AB - AIM: The aim of this study was to determine if the disease-free interval after initial surgical resection has any useful prognostic value for recurrent endometrial carcinoma patients. PATIENTS AND METHODS: Between 1998 and 2007, complete resection of endometrial carcinoma was achieved in 536 cases at the Departments of Obstetrics and Gynecology of the Osaka University and Osaka Rosai Hospitals of Osaka, Japan. Clinical characteristics of these cases were retrospectively reviewed. RESULTS: Recurrence was subsequently detected in 54 cases. Overall survival after recurrence in 27 patients with recurrences earlier than 12 months who received no postoperative therapy, radiation, and chemotherapy as an adjuvant therapy were significantly shorter than that of those with recurrences later than 12 months with similar treatments. Multivariate analysis demonstrated that the disease-free interval was an independent factor for prognosis. CONCLUSION: We demonstrate a significantly worse prognosis in cases with early versus late recurrence of resected endometrial carcinomas, irrespective of the type of adjuvant therapy. PMID- 21036763 TI - High prevalence of human anti-mouse antibodies in the serum of colorectal cancer patients. AB - BACKGROUND: Monoclonal antibody treatment induces the expression of human anti mouse antibodies (HAMA), which in turn interfere with the therapy. However, whether HAMAs are expressed before the initiation of antibody therapy in patients with colorectal cancer remains unknown. MATERIALS AND METHODS: Serum samples were collected from 40 patients diagnosed with colorectal cancer. Serum samples from 157 individuals without cancer were used as controls. None of the patients received imaging or therapeutic antibodies before the study. The expression of HAMAs was evaluated by ELISA with murine immunoglobulin G1 (mIgG)1, mIgG2a and mIgG2b as the antigen. RESULTS: Of the 40 colorectal cancer patients, 9 (22.5%) expressed either IgG- or IgM-type HAMAs while only 13/157 (8.2%) of the individuals without cancer expressed the HAMAs (p<0.05). CONCLUSION: HAMAs are prevalent in the serum of colorectal cancer patients even before antibody administration. Medical practitioners should be alert to the possibility of HAMA expression when administering antibody therapy. PMID- 21036764 TI - Carboplatin plus weekly paclitaxel treatment in non-small cell lung cancer patients with interstitial lung disease. AB - BACKGROUND: Since advanced non-small cell lung cancer (NSCLC) patients with the interstitial lung disease (ILD) have been excluded from clinical trials, it is uncertain whether chemotherapy really provides a benefit to these patients. PATIENTS AND METHODS: Fifteen advanced NSCLC patients with ILD that was detected on the chest X-rays were enrolled in this study. Carboplatin plus paclitaxel was administered by two methods (method A or method B). Method A: Carboplatin (AUC 6, day 1) and paclitaxel (70 mg/m(2), days 1, 8, 15) were administered every four weeks. Method B: Carboplatin (AUC 2, day 1, 8, 15) and paclitaxel (60 mg/m(2), days 1, 8, 15) were administered every four weeks. RESULTS: The response rate and the disease control rate were 33% and 53%. The median progression-free survival and the median overall survival time were 2.5 months and 7.0 months, respectively. The hematological toxicities were tolerable, but a grade 3 or higher pneumonitis was observed in 4 patients (27%). CONCLUSION: Carboplatin plus weekly paclitaxel must be administered carefully to advanced NSCLC patients with ILD that is detected on chest X-rays after a sufficient evaluation of the risks and the benefits. PMID- 21036766 TI - Prognostic value of IL-6 in localized prostatic cancer. AB - AIM: The usefulness of interleukin 6 (IL-6) and its soluble receptor IL-6sR in the prediction of the biochemical recurrence was evaluated in patients with prostate cancer treated with radical prostatectomy. PATIENTS AND METHODS: IL-6 and sIL-6R serum levels were measured in 96 patients with prostate cancer. RESULTS: Using the log-rank test, it was evident that patients with preoperative serum levels of IL-6 higher than 1.2 pg/ml had a significantly increased probability of biochemical recurrence (p=0.031). We also observed that the Gleason score was associated with the risk of progression (p=0.033), but no relation was observed with TNM classification, PSA, % free PSA or sIL-6R. In a multivariate analysis, only IL-6 serum levels remained as a predictor of biochemical recurrence (p=0.040). CONCLUSION: The results presented here demonstrated the usefulness of IL-6 in predicting the biochemical progression of prostate cancer, pointing towards an association between inflammation and the aggressiveness of the tumor. PMID- 21036765 TI - Immunochemical staining of MT2-MMP correlates positively to angiogenesis of human esophageal cancer. AB - Matrix metalloproteinases (MMPs) play an important role in the pathological processes of degradation of extracellular matrix and destruction of basement membrane, which leads to tumor invasion and metastasis. In the present study, we investigated membrane-type 2 MMP (MT2-MMP) expression pattern in esophageal cancer tissues collected from 103 patients, and explored MT2-MMP expression pattern in correlation to patients' clinicopathological features, intratumoral angiogenesis and postoperative prognoses. The intensity of immunochemical staining of MT2-MMP was significantly positively correlated to the intratumoral angiogenesis of esophageal cancer tissues. Positive MT2-MMP immunoreactions were found in 85.4% of total tumor sections, whereas none or very weak MT2-MMP staining occurred in normal esophageal tissues. In addition, MT2-MMP immunochemical intensities were significantly correlated to tumor size, but not to patient's gender, age, invasion depth, lymph node metastasis and distant metastasis. Moreover, MT2-MMP levels could not be applied for predicting patients' survival rate although the H-score cut-off value showed the overall survival rate of patients with low MT2-MMP protein level to be better than those with high MT2-MMP protein level. PMID- 21036767 TI - Relationship between thymidylate synthase (TYMS) gene polymorphism and TYMS protein levels in patients with high-risk breast cancer. AB - The thymidylate synthase gene (TYMS) has three functional polymorphisms which are associated with TYMS expression. To explore the predictability of TYMS polymorphisms for the sensitivity and toxicity of 5-fluorouracil (5-FU) in breast cancer patients, this study investigated the association between TYMS polymorphisms and TYMS protein expression in normal and tumour tissue specimens from 49 lymph node-positive breast cancer patients. An analysis of the TYMS 3' UTR polymorphism showed that level of TYMS protein in normal tissue with the +6 bp/+6 bp genotype was significantly higher than that for the -6 bp/+6 bp genotype. Tumour tissue with the +6 bp/+6 bp genotype had a significantly higher TYMS protein expression than did those with other genotypes. These findings suggest that breast cancer patients with the TYMS 3'-UTR +6 bp/+6 bp polymorphism whose tumours show a 6 bp deletion within TYMS 3'-UTR represent a group that may derive the most benefit from 5-FU chemotherapy.